i

ANESTHESIA AND PERIOPERATIVE CARE

OF THE COMBAT CASUALTY
ii

The Coat of Arms

1818

Medical Department of the Army

A 1976 etching by Vassil Ekimov of an

original color print that appeared in

The Military Surgeon, Vol XLI, No 2, 1917
iii

The first line of medical defense in wartime is the combat

medic. Although in ancient times medics carried the caduceus

into battle to signify the neutral, humanitarian nature of

their tasks, they have never been immune to the perils of

war. They have made the highest sacrifices to save the lives

of others, and their dedication to the wounded soldier is

the foundation of military medical care.
iv

Textbook of Military Medicine

Published by the

Office of The Surgeon General

Department of the Army, United States of America

Editor in Chief

Brigadier General Russ Zajtchuk, MC, U.S. Army

Director, Borden Institute

Commanding General

U.S. Army Medical Research and Materiel Command

Professor of Surgery

F. Edward Hébert School of Medicine

Uniformed Services University of the Health Sciences

Officer in Charge and Managing Editor

Colonel Ronald F. Bellamy, MC, U.S. Army

Borden Institute

Associate Professor of Military Medicine,

Associate Professor of Surgery,

F. Edward Hébert School of Medicine

Uniformed Services University of the Health Sciences
v

The TMM Series

Part I. Warfare, Weaponry, and the Casualty

Medical Consequences of Nuclear Warfare

(1989)

Conventional Warfare: Ballistic, Blast, and Burn

Injuries (1991)

Military Psychiatry: Preparing in Peace for War

(1994)

War Psychiatry (1995)

Medical Aspects of Chemical and Biological

Warfare

Military Medical Ethics

Part II. Principles of Medical Command and Support

Medicine and War

Medicine in Low-Intensity Conflict

Part III. Disease and the Environment

Occupational Health: The Soldier and the

Industrial Base (1993)

Military Dermatology (1994)

Mobilization and Deployment

Environmental Hazards and Military Operations

Part IV. Surgical Combat Casualty Care

Anesthesia and Perioperative Care of the

Combat Casualty (1995)

Combat Injuries to the Head, Face, and Neck

Combat Injuries to the Trunk

Combat Injuries to the Extremities and Spine

Rehabilitation of the Injured Soldier
vi

The care of the combat casualty is a multifaceted endeavor in which the acts of individual medical personnel

are inextricably linked. A continuum of care must exist from the most junior medic in the field through

evacuation to the most senior specialist in a deployable hospital. The essential prerequisites at all echelons

of care are courage, endurance, skill, knowledge, and above all, devotion to the well-being of the casualty.
vii

ANESTHESIA AND PERIOPERATIVE CARE

OF THE COMBAT CASUALTY

Office of The Surgeon General

United States Army

Falls Church, Virginia

Walter Reed Army Medical Center

Washington, D.C.

United States Army Medical Department Center and School

Fort Sam Houston, Texas

Uniformed Services University of the Health Sciences

Bethesda, Maryland

1995

Specialty Editors

BRIGADIER GENERAL RUSS ZAJTCHUK

Medical Corps, U.S. Army

CHRISTOPHER M. GRANDE, M.D.

Executive Director

International Trauma Anesthesia and Critical Care Society
viii

Editorial Staff: Lorraine B. Davis

Senior Editor

Colleen Mathews Quick

Associate Editor/Writer

Nancy Michel

Copyeditor

This volume was prepared for military medical educational use. The focus of the information

is to foster discussion that may form the basis of doctrine and policy. The volume does not

constitute official policy of the United States Department of Defense.

Dosage Selection:

The authors and publisher have made every effort to ensure the accuracy of dosages cited herein.

However, it is the responsibility of every practitioner to consult appropriate information sources

to ascertain correct dosages for each clinical situation, especially for new or unfamiliar drugs and

procedures. The authors, editors, publisher, and the Department of Defense cannot be held

responsible for any errors found in this book.

Use of Trade or Brand Names:

Use of trade or brand names in this publication is for illustrative purposes only and does not

imply endorsement by the Department of Defense.

Neutral Language:

Unless this publication states otherwise, masculine nouns and pronouns do not refer exclusively

to men

CERTAIN PARTS OF THIS PUBLICATION PERTAIN TO COPYRIGHT RESTRICTIONS.

ALL RIGHTS RESERVED.

NO COPYRIGHTED PARTS OF THIS PUBLICATION MAY BE REPRODUCED OR

TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL

(INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND

RETRIEVAL SYSTEM) WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER OR

COPYRIGHT OWNER

Published by the Office of The Surgeon General at TMM Publications

Borden Institute

Walter Reed Army Medical Center

Washington, DC 20307-5001

Library of Congress Cataloging–in–Publication Data

Anesthesia and perioperative care of the combat casualty / prepared

under the direction of Russ Zajtchuk.

p. cm. — (Textbook of military medicine. Part IV, Surgical

combat casualty care ; [v. 1])

Includes bibliographical references and index.

1. Surgery, Military. 2. Anesthesiology. 3. Therapeutics

Surgical. 4. War wounds—Surgery. I. Zajtchuk, Russ. II. Series.

[DNLM: 1. Anesthesia. 2. Preoperative Care. 3. Intraoperative

Care. 4. Military Medicine. 5. Postoperative Care. UH 390 T355

pt.4 1995 v. 1]

RD153.A54 1995

617.9'6799—dc20

DNLM/DLC

for Library of Congress 95-41596

CIP

PRINTED IN THE UNITED STATES OF AMERICA

04, 03, 02, 01, 00, 99, 98, 97, 96 5 4 3 2 1
ix

Foreword by The Surgeon General xi

Preface xiii

Patient Flow in a Theater of Operations xv

1. Combat Trauma Overview 1

2. Combat Anesthesia Overview 43

3. Airway Management 55

4. Hemorrhage, Shock, and Fluid Resuscitation 81

5. Physiological Monitoring 101

6. Deployable Hospitals 115

7. Military Anesthesia Machines 141

8. Closed-Circuit Anesthesia 175

9. Inhalational Anesthesia 187

10. Intravenous Anesthesia 211

11. Neuromuscular Blocking Agents 235

12. Regional Anesthesia 251

13. Perioperative Pain Management 287

14. Transfusion Therapy 321

15. Military Transfusion Practice 341

16. Neurological Injuries 375

17. Eye Injuries 425

18. Injuries to the Face and Neck 437

19. Thoracic Injuries 455

20. Abdominal Injuries 479

21. Extremity Injuries 499

22. Burn Injuries 521

23. Metabolic Derangements and Nutritional Support 543

24. The Syndromes of Systemic Inflammatory Response

and Multiple Organ Dysfunction 597

Contents
x

25. Acute Respiratory Failure and Ventilatory Management 667

26. Acute Renal Failure 709

27. Military Medical Evacuation 751

28. Systemic Hypothermia 787

29. Malignant Hyperthermia 811

30. Anesthesia for Casualties of Chemical Warfare Agents 833

31. A Brief History of Military Anesthesia 855

Acronyms and Abbreviations 897

Index 901
xi

Foreword

Lieutenant General Alcide M. LaNoue

The Surgeon General

U.S. Army

December 1995

Washington, D.C.

This is an exciting time to be in the U.S. Army Medical Department. Not

since the end of World War II have such fundamental changes occurred:

decreased resources and personnel; increased emphasis on support of

forces deployed in the field; uncertainty as to the nature of the next war in

which we will be providing medical support—a consequence of the

dissolution of the Cold War; and overlaying all, the fundamental changes

likely to be wrought by applications of advanced technology. These

factors will change the provision of combat casualty care in ways that we

can only speculate about. But we must not make changes simply for the

sake of change; we must keep faithful to the fundamental principles of

military medicine. The Textbook of Military Medicine is a repository of the

science and art of military medicine, and as such is our anchor in this vast

sea of change. By keeping the historical, factual, and scientific bases of

military medicine readily accessible in this series of textbooks, the lessons

learned in previous wars will not need to be relearned—at the casualty’s

expense—in future wars.

The U.S. Army does not recognize any one group of practitioners as

preeminent in the management of combat casualties. Rather, combat

casualty care occurs along a spectrum ranging from buddy aid on the

battlefield to definitive care at hospitals in the continental United States.

For this reason, this textbook, Anesthesia and Perioperative Care of the Combat

Casualty, is not restricted merely to the technical aspects of providing

anesthetics; instead, it encompasses the constellation of actions that, taken

together, ensure an optimal outcome for the casualty.

The probability of massive wars of prolonged duration has decreased.

These wars were dominated by attrition of personnel, in which conserving

the fighting strength was the major focus of the U.S. Army Medical

Department. In future wars, however, the medical department will

probably be judged more by its ability to save lives. Thus this book, with

its emphasis on lifesaving intervention, is especially timely. Nevertheless,

the true contribution of anesthesia in military medicine is probably not

found in mortality and morbidity statistics but in something more difficult

to measure and perhaps even more important: the alleviation of pain and

suffering.

I strongly recommend that all commanders and medical officers read

this volume with an open mind. Massive changes are occurring in military

medicine. Medical officers of the future will encounter numerous changes

in doctrine and advanced technology; our willingness to respond to these

opportunities will be necessary to ensure that our soldiers receive nothing

less than the best combat casualty care.
xii
xiii

Preface

December 1995

Washington, D.C.

Brigadier General Russ Zajtchuk

Medical Corps, U.S. Army

The extent to which the specialty of anesthesiology has come of age is

apparent when we consider that no official history was published on the science

and practice of providing anesthesia in World War II. Information on anesthesia

was contained in single chapters in other specialty volumes. Now we have a 31-

chapter volume, Anesthesia and Perioperative Care of the Combat Casualty. This

textbook is not limited to the purely technical aspects of anesthesia practice.

Instead, except for details of surgical technique and rehabilitation, it portrays

the entire expanse of modern combat casualty care. In a real sense, this volume

of the Textbook of Military Medicine can be viewed as a treatise on combat casualty

care for the military anesthesia provider. Throughout the textbook, the term

“military anesthesia provider” has been used whenever possible to underline

the fact that in the U.S. Army Medical Department, as well as in the other

services, the provision of anesthesia is the joint effort of officers drawn from two

corps: medical and nursing.

Because military medicine is organized by echelon, the provision of combat

casualty care is best understood as a continuum to which each echelon makes an

essential contribution. This is the fundamental difference between combat

casualty care in military medicine and trauma management in civilian hospitals,

and this approach must be clearly understood in advance by all healthcare

providers in the military medical services. The best efforts of hospital-based

practitioners will be to no avail if lifesaving first aid on the battlefield is

inadequate or if evacuation from the battlefield is not timely. Likewise, the best

battlefield first aid or the most expeditious evacuation will be wasted unless

hospital care is correspondingly excellent. An optimal outcome for the casualty

is ensured only by the entire constellation of actions that compose combat

casualty care.

The Textbook of Military Medicine is honored to publish illustrations of combat

casualties from two sources that were compiled during the Vietnam War: the

Wound Data and Munitions Effectiveness Team (WDMET) collection, a vast

databank that was compiled at the direction of General Creighton Abrams,

which contains information on nearly 8,000 casualties; and the Swan Vietnam

Surgical Slide Set, which was compiled by Colonel Kenneth Swan, Medical

Corps, U.S. Army Reserve, in 1970. This volume contains more than 100 neverbefore-published illustrations from these sources.

This book’s long gestation began while Donald P. Jenkins, Ph.D., was Managing Editor. During the book’s formative years, Colonel Brian C. Condon,

Medical Corps, U.S. Army (retired), in his capacity then as Anesthesia Consultant to The U.S. Army Surgeon General, and Christopher M. Grande, M.D., of the

International Trauma Anesthesia and Critical Care Society, recruited authors

and guided the development of their chapters. More recently, however, at my

request, Captain W. Clayton Petty, Medical Corps, U.S. Navy, and Colonel

Denver E. Perkins, Medical Corps, U.S. Army, provided the professional advice

and the de novo chapters that made publication possible. The U.S. Army

Medical Department owes each of these individuals a debt of gratitude.
xiv

The current medical system to support the U.S. Army at war is a

continuum from the forward line of troops through the continental United States; it serves as a primary source of trained replacements during the early stages of a major conflict. The system is

designed to optimize the return to duty of the maximum number

of trained combat soldiers at the lowest possible level. Farforward stabilization helps to maintain the physiology of injured

soldiers who are unlikely to return to duty and allows for their

rapid evacuation from the battlefield without needless sacrifice

of life or function.
xv

Medical Force 2000 (MF2K)

PATIENT FLOW IN A THEATER OF OPERATIONS

E: Echelon

EAC: Echelon Above Corps

FST: Forward Surgical Team

MASF: Mobile Aeromedical Staging Facility, USAF

Med Co: Medical Company

RTD: Return to Duty

ASF: Aeromedical Staging Facility, USAF

ASMB: Area Support Medical Battalion

ASMC: Area Support Medical Company

BAS: Battalion Aid Station

CM: Combat Medic

CONUS: Continental United States

CZ: Combat Zone

Cbt 

Medic

BAS

Med Co

CSH

MASF

GH

FH

Med Co

ASMC/ASMB

ASMC/ASMB

xx

xxx

x

RTD

RTD

RTD

RTD

RTD

RTD

COMMUNICATION 

ZONE

 CORPS

SUPPORT

AREA

 DIVISION

SUPPORT

AREA

 BRIGADE

SUPPORT

AREA

CZ

1st E

2nd E

3rd E

4th E

 CONUS 

FST

 UNIT

SUPPORT

AREA

COMMZ

ASF
1

Combat Trauma Overview

Chapter 1

COMBAT TRAUMA OVERVIEW

RONALD F. BELLAMY, M.D.*

INTRODUCTION

ATTRITION IN WAR

Historical Aspects

Importance of Attrition due to Battle Injury

Magnitude of Attrition

THE NATURE OF COMBAT INJURY

Mechanisms of Injury

Sources of Penetrating Missiles

Distribution of Missile Wounds by Body Surface

Wound Depth

MEDICAL OUTCOME OF COMBAT INJURY

Killed in Action

Died of Wounds

Absence of a “Golden Hour” in Combat Trauma

Historical Trends in Combat Mortality

Outcome of Specific Body-Region Injuries

Morbidity

Injury Severity Assessment

Pathophysiological Causes of Death

THE ANESTHESIOLOGIST AND COMBAT CASUALTY CARE

Advanced Trauma Life Support Course

Specific Aspects of Advanced Trauma Life Support

SUMMARY

*Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

2

INTRODUCTION

For military anesthesiologists to assume responsibilities that transcend their traditional role in field

hospitals, they will need a broad understanding of

the problems of medical support in the theater of

operations. The military anesthesiologist who is

aware of what it is that makes military medicine

unique and who is well versed in the management

of trauma will be able to make important contributions to many of the problems that arise in combat

casualty care. This chapter gives an epidemiologically oriented overview of that vast expanse of

human misery treated by the specialty of military

medicine, with special emphasis on combat trauma

sustained in conventional land warfare. The stage

will then be set for the ensuing chapters, with their

detailed discussions of resuscitation, with special

emphasis on emergency lifesaving interventions;

the practice of anesthesia in the combat zone; anesthetic management of specific types of combat injuries; and critical-care medicine.

ATTRITION IN WAR

The military anesthesiologist’s principal wartime

role in the theater of operations will be, of course, to

care for casualties with combat trauma, but it needs

to be emphasized that such injuries constitute only

one of the sources of attrition that can potentially

destroy an army. The important sources of personnel attrition in the combat zone are (a) enemy action,

which by definition includes not only battle injuries

but also being captured; (b) disease; (c) nonbattle

injury, which also includes the effect of a hostile

environment; (d) desertion; and (e) administrative

action that results in a soldier’s being transferred

from the unit in question (Figure 1-1). Not all the

sources of attrition have medical implications; for

the purpose of this chapter, only battle injury, disease, and nonbattle injury will be considered.

It should be noted that the word “casualty” was

not used in the preceding paragraph. In the past, in

most armies, a casualty was defined as a soldier

who had been either physically injured by enemy

action or captured. It was therefore inappropriate

to refer to “disease casualties” or “psychiatric casualties.” The U.S. Army Medical Department

(AMEDD) has recently changed the definition of

casualty: a combat-zone soldier who is noneffective

for any medical reason.1 This chapter uses the word

casualty in its traditional meaning whenever historical data are studied.

Although it is usual to classify battle injury as

injury that has resulted from the hostile actions of a

military enemy, many battle injuries are actually

inflicted by the casualty’s own side in the confusion

of the fighting. Perhaps because of the pejorative

and emotional connotation that surrounds such casualties of so-called “friendly fire,” their numerical

importance as a source of attrition has been somewhat downplayed in the past. Although unofficial

guidance on casualties of friendly fire suggests that

0.5% of battle casualties may fall into this category,

more recent studies indicate that the actual prevalence is more like 10% to 20%.2

Historical Aspects

When viewed from the perspective of military

history, disease and its common companion, a hostile environment, have been far greater threats to

soldiers’ health than hostile acts of a military enFig. 1-1. Possible sources of attrition in a military unit.

The major categories are enemy action, disease, nonbattle

injury, desertion, and administrative action. Psychiatric

casualties are placed in the disease category. Soldiers

who are missing in action can ultimately be placed in the

captured, fatally wounded, or desertion categories, or

they can be returned to duty.

DISEASE

Died

Captured

Total

Wounded

Fatally

Wounded ENEMY ACTION

Fatally

Injured

NONBATTLE

INJURY

DESERTION

ADMINISTRATIVE

ACTION

Return

to Duty

Missing

Psychiatric
3

Combat Trauma Overview

TABLE 1-1

ATTRITION IN THE GRANDE ARMÈE IN THE

RUSSIA CAMPAIGN OF 1812

Source of Attrition Number Affected

Died of hunger, exhaustion, cold,

or disease 200,000

Killed in battle 100,000

Prisoners of war 100,000

Deserters 50,000

In hospital 50,000

Data source: Bodart G. Losses of Life in Modern Wars. Oxford,

England: Clarendon Press; 1916: 127.

emy. There is no better example of this than the

disaster that befell Napoleon’s Grande Armèe in

1812. Napoleon started his invasion of Russia in

June with more than 600,000 soldiers and finished

in December with about 100,000. One assessment of

what happened to the missing 500,000 is given in

Table 1-1.

3

 Most of these losses were from the group

of armies under Napoleon’s personal command: of

450,000 soldiers, only 25,000 are believed to have

survived.4 It is part of the mythology surrounding

the campaign of 1812 that it was the cold of the

Russian winter more than any other factor that

destroyed the Grande Armèe, but this explanation

was a self-serving fabrication of Napoleon’s. More

than two thirds of the Grande Armèe had been lost

before the end of the summer of 1812 and before the

major battle of the campaign, at Borodino on 7

September 1812. Heat and disease (primarily typhus and dysentery) during the summer, not cold

and starvation during the autumn, caused the catastrophic attrition.5 Disease wiped out the Grande

Armèe because Napoleon’s logistical support was

predicated on an unrealistically optimistic appraisal

of the campaign’s duration (eg, food was available

for only 3 wk) and, worse, his medical support was

inadequate—even given the primitive nature of

military medicine in the early 19th century.

The attrition of the Grande Armèe in Russia was

by no means unique in the history of warfare, but

lest it be thought that this experience is totally

irrelevant to the modern age, the following example

of attrition from World War II may be instructive.

For brilliance of leadership, the North African campaign of the renowned German general Erwin

Rommel is held in the greatest esteem by military

authorities. Rommel ultimately lost, but his defeat

is usually attributed to the overwhelming materiel

and personnel strength of his adversaries. What is

not generally appreciated is that Rommel’s manpower problems were much of his own making.

Table 1-2 shows the sources of attrition in Rommel’s

main fighting force—Panzerarmee Afrika—for the

15-month period starting in October 1941.6

For every German soldier that Rommel lost to

battle injury, almost three were lost to disease.

While the destruction of the Grande Armèe was

fundamentally due to Napoleon’s callous indifference to the needs of his soldiers, the attrition of

Panzerarmee Afrika, although partially due to the

hostile environment of the North African desert,

was primarily the result of Rommel’s ignorant indifference to his own and his soldiers’ health. He

never recognized what disease was doing to the

strength of his army, and he clearly never understood that it is the commander and not the military

medical service who is ultimately responsible for

the health of the soldier.7 It is not a little ironic that

leaders such as Napoleon and Rommel are held in

such high regard by the military profession when,

in fact, they were a worse threat than the enemy to

their own men.

Importance of Attrition due to Battle Injury

The relative importance of losses due to battle

injury and from disease and nonbattle injury is

determined by a variety of factors, including

• the presence of endemic diseases,

• the climate and the environment,

TABLE 1-2

ATTRITION IN PANZERARMEE AFRIKA*

OCTOBER 1941–DECEMBER 1942

Source of Attrition Number Affected

Killed 4,524

Wounded† 16,824

Missing‡ 13,024

Sick§ 88,320

*Average strength 43,000

†About 95% required evacuation to Europe

‡About 50% were probably captured; the remainder were killed

§Required admission to a hospital; at least 28,000 required

evacuation to Europe

Data source: Fischer H. Der deutsche Sanitätsdienst 1921–1945.

Vol 3. Osnabrück, Germany: Biblio Verlag; 1983: 1517, 1535.
Anesthesia and Perioperative Care of the Combat Casualty

4

• the duration of the deployment, and

• the nature of the tactical mission and the

intensity of the fighting.

It is certainly possible for battle injury to be the

major source of attrition in short but fiercely fought

campaigns. The Battle of Cannae in 216 BC, in which

a Roman army of some 86,000 was totally destroyed

by Hannibal, with the loss of 50,000 killed and

25,000 captured, is a good example of circumstances

in which battle injury is the predominant source of

attrition in a campaign.8 A more recent example of

the importance of the intensity of the fighting as a

determinant of attrition is the German airborne

attack on the Island of Crete. Over a 10-day period

in May 1941, a German force of about 22,000 lost no

fewer than 6,000 men: 4,000 killed and 2,000

wounded. The first day alone saw 4,000 casualties

among the 8,000 airborne troops who had arrived

on Crete.9 Needless to say, losses due to disease

during this period were a minor component of the

overall attrition.

Thus, given (a) intense fighting, (b) military leadership that recognizes its responsibility for the health

of the men, (c) a knowledgeable and efficient medical

service, and (d) the good fortune to fight in a climate

and an environment that are not especially hostile,

disease and nonbattle injury may not be the predominant sources of attrition. The British experience in

the early weeks of the Normandy invasion in the

summer of 1944 may be taken as an example. Figure 1-2 shows the partition of the British army’s

losses (rounded off to the nearest 500) during the 7

weeks after the landing on D day, 6 June 1944.

Battle injury caused approximately 56% of the total

British attrition due to medical reasons (missing

and prisoner casualties are not considered).10 Given

enlightened leadership and an effective medical

service, attrition due to battle injury is likely to be of

greater importance than would be suggested from

considerations based on the U.S. experience in, for

example, the Spanish–American War—in which

battle injury caused fewer than 7% of the total

deaths.11

Magnitude of Attrition

To determine the medical assets (eg, the number

of anesthesiologists) required in a war, an estimate

of the expected number of battle, nonbattle, and

disease casualties is needed. Although the medical

threat from disease and the environment can be

forecasted if the prevalence of endemic diseases in

the theater of operation and its climate are known

with some accuracy, the estimation of battle casualty rates is at best an art. Battle casualty rates, like

those for disease and nonbattle injury, are usually

given as an incidence (ie, the number of casualties

per 1,000 soldiers per day, or the percentage of a

unit of known size per day). The current practice is

to use computer models that incorporate historical

data to estimate rates for a unit of given size carrying out a specified tactical mission (eg, an airborne

battalion assaulting a fortified position, or a division engaged in an opposed river crossing). The

major deficiency of this empirical approach is that

the data are from unique historical events and may

not be applicable to a hypothetical future combat

operation. What would have been the result if data

gathered during the assault of the Siegfried line

(1944–1945) had been used to predict the number of

casualties before U.S. forces attacked the Saddam line

in Kuwait in February 1991? A prediction based on

the historical data would have overestimated by

several hundredfold the actual number of casualties

Fig. 1-2. Partition of the medical sources of attrition for

the British army in Normandy, 6 June through 31 July

1944. Battle injury was the major source of attrition in the

high-intensity campaign. Data source: Crew FAE. Campaigns. North-West Europe. Vol 4. London, England: The

Army Medical Services, Her Majesty’s Stationery Office;

1962: 597, 608, 610.

8,000 Killed 65,000 Admitted

73,000

33,000

Wounded

6,000 

Injured

17,500 

Sick

6,500 

Psychiatric

28,000

Evacuated

2,000 Died 3,000 

Returned to Duty
5

Combat Trauma Overview

for this simple reason: the defense of the Siegfried line

was conducted by well-trained and highly motivated

German professionals, while the Saddam line was

defended by ineffective Iraqi draftees.

Intensity

Because it is difficult to predict casualty rates for

all warfighting scenarios, descriptive terms such as

“intensity” have commonly been used as qualitative indicators of expected attrition. Using this

approach, it is possible to conceive of a hypothetical

spectrum of combat intensities extending from

peacekeeping operations to global nuclear war.12

Between the extremes are various intensities of conventional war. The “low”-intensity end of the spectrum is typified by the Vietnam War, with its multitude of tiny search-and-destroy missions; the 1944

Normandy invasion and the gigantic air-land battle

that occurred in the summer of 1943 at Kursk in

central Russia are both examples of the “high”-

intensity end.

The concept of intensity is meaningful only when

viewed as a quasi-statistical term that depends on

both the duration of the combat and the size of the

population at risk. The term is meaningless when

applied to a single soldier or to a short, small-unit

combat action. For a soldier who is killed in action,

the combat was of maximum intensity regardless of

whether his death occurred in a low-intensity peacekeeping operation or a high-intensity global nuclear

war. The combat action in Mogadishu, Somalia, on 3

October 1993 (during which 18 U.S. Army Rangers

were killed and 70 were wounded during a companysized operation) was no doubt considered very intense by the participants. However, a single such

action during a several-month-long deployment by

a brigade- or division-sized unit would qualify the

entire operation as one of very low intensity. On the

other hand, if the combat action in Mogadishu had

been repeated daily over months by hundreds of

company-sized units, the level of attrition would

have been that of a high-intensity war.

The purpose of the Venn diagrams in Figure 1-3

is to contrast the trauma-generating potential of

three very different sources: a modern U.S. city, a

low-intensity war, and a high-intensity war. The

city is represented by San Francisco in 1977.13 From

a population of about 550,000, the probability of

becoming a casualty (defined as either being killed

at the scene or sustaining an injury that required

admission to a hospital) was about 1 in 78. Of all

trauma victims, 6% were fatally injured. The lowintensity war is represented by the U.S. Army in the

Vietnam War for the year 1969.14–16 The average

troop strength was about 326,000 and the overall

probability of becoming a battle casualty was slightly

more than 1 in 10; for soldiers who were casualties,

the probability of dying was about 1 in 5. The Iraqi

army (but not the U.S. Army) experienced highintensity attrition during the Persian Gulf War.17

Approximately 500,000 Iraqis were deployed in the

Kuwaiti theater of operation, of whom about 100,000

were killed and 100,000 were taken prisoner. The

Venn diagram that portrays the Iraqi experience

makes clear the truth of the famous observation by

the noted Russian military surgeon Nikolai

Ivanovich Pirogov (1810–1881) that “war is an epidemic of injuries.”18

Fig. 1-3. The largest circle in each Venn diagram is proportional to the population at risk; the inner circle is

proportional to the number of casualties, and the black

circles are proportional to the number of fatalities. The

Iraqi data are provisional. We have assumed that 100,000

have been killed and 100,000 wounded or taken prisoner.

Civilian Trauma

San Francisco, 1977

Low-Intensity War

U.S. Army, Vietnam, 1969

High-Intensity War

Iraqi Army, Kuwait, 1991
Anesthesia and Perioperative Care of the Combat Casualty

6

Battle Casualty Rates

Casualty rates can be calculated for the three

examples shown in Figure 1-3, but it should be

understood that such overall average rates ignore

not only day-to-day (ie, stochastic) fluctuations but

also unique events (eg, battles) and disasters (eg,

earthquakes). They are statistical generalizations

and are useful only for illustrative purposes. Calculated casualty rates are about 0.0035% per day

for the city, 0.025% per day in the low-intensity

war, and 0.7% per day in the high-intensity war.

The respective rates for civilian trauma and lowintensity war, and the respective rates for lowintensity and high-intensity wars, each differ by

about one order of magnitude. Although the city

selected—San Francisco in 1977—had a notably

benign milieu given the violence-plagued U.S.

cities of the last decade of the 20th century, an

increase of the rate much beyond 0.004% or 0.005%

per day is unlikely. By way of comparison, the

overall attrition rate for Napoleon’s Grande Armèe

in Russia was from 1% to 3% per day; for

Panzerarmee Afrika, attrition due to enemy action

averaged about 0.15% per day; and for battle injury

in the British army in Normandy, the average rate

was about 0.18% per day. A battle casualty rate of

0.17% per day characterized German attrition in the

first 100 days of their attack on the Soviet Union in

1941.9 In actual numbers, this rate meant about

5,500 casualties per day—more than 10-fold higher

than the total U.S. Army losses in the Persian Gulf

War. It should be understood that these rates are

meaningful only for large populations of soldiers

engaged in combat for prolonged periods. They are

presented for illustrative purposes and are not

equivalent to the official projected rates found in

U.S. Army Field Manual 8-55, Planning for Health

Service Support.1

Although there is no completely successful approach to predicting attrition, some well-documented empirical observations on attrition have

been made:

• Battle casualty rates are inversely proportional to the size of the unit; for example, a

battalion will have a higher rate than a division.12 There is an obvious explanation for

this fact: the smaller the combat unit, the

fewer the combat support and combat service

support personnel who, by virtue of their

duties, are not exposed to direct enemy fire.

• When combat units are actually in contact

with the enemy, division battle casualty rates

in high-intensity war have usually been about

1% per day, although on rare occasions rates

of up to 10% per day have been observed.

Corresponding brigade and battalion rates are

3% and 10% per day, respectively. Army rates

can be expected to be less than 1% per day.19

• Disease and nonbattle injury rates occur at

a constant rate, which ranges from 0.1% to

0.3% per day to 0.5% per day when (a)

combat operations interfere with the provision of effective preventive medicine or (b)

the environment is especially hostile.19

To put the estimation of casualty rates in practical perspective, consider the following example. A

brigade-sized force (about 3,000 men) is engaged in

day-long, high-intensity combat. Given a battle

casualty rate of 3% per day, 100 casualties may

be expected. In addition, 15 soldiers can be expected to be lost because of disease. Not all the

combat casualties will require anesthetic management, because some of them will have been killed

and some will have minor wounds not requiring an

anesthetic.

THE NATURE OF COMBAT INJURY

Combat injury and civilian trauma differ in significant respects. The nature of combat injury

depends on several factors: (a) the mechanisms of

injury, of which penetrating injury is the predominant; (b) the source of penetrating missiles, of

which fragments and bullets predominate; (c) the

distribution of missile wounds on the body surface;

and (d) the relation between mortality and wound

location: specifically, which internal organs have

been struck.

Mechanisms of Injury

The mechanisms of injury found in conventional

land warfare—penetrating, blast, blunt, and thermal—do not differ from the mechanisms that cause

injury in civilian life. What is different is the relative prevalence of the mechanisms. While a blunt

mechanism is the most important source of injury

for civilians, trauma inflicted during combat is overwhelmingly penetrating in nature (Figure 1-4). Data
7

Combat Trauma Overview

100

80

60

40

20

Percentage of Combat Casualties

0

World War II Korean War Vietnam War

Penetrating

Blast

Blunt

Thermal

Unknown

World War II: for 600,000 casualties surviving to receive medical care1

Korean War: all combat casualties2

Vietnam War: January 1965 to June 1970; for casualties surviving to receive medical care3; injuries were either penetrating or other

than penetrating

Fig. 1-4. Mechanism of injury in US Army combat casualties. Penetrating missiles were the source of injury in 85% to

95% of casualties. Data sources: (1) Reister FA. Medical Statistics in World War II. Washington, DC: Department of the

Army, Office of The Surgeon General; 1975: Table 7, p 90 and Table 17, p 202. (2) Reister FA. Battle Casualties and Medical

Statistics: US Army Experience in Korea. Washington, DC: Department of the Army, The Surgeon General; 1973: 45. (3)

Neel S. Medical Support of the US Army in Vietnam 1965–1970. Washington, DC: Department of the Army; 1973: 54.

compiled from the U.S. Army’s records for World

War II,20 the Korean War,21 and the Vietnam War22

indicate that penetrating missiles are the mechanism of injury in about 90% of all battle casualties

(ie, soldiers who are injured as a result of the hostile

actions of a military enemy).

It is commonly thought that “blast” is a frequent

cause of combat trauma, but this is a misconception. It no doubt springs from popular images of

people being blown apart by powerful explosions.

Although it is true that soldiers in close proximity

to the detonation of a large explosive munition may

sustain blast and thermal injuries, penetrating missile wounds constitute the major medical treatment

problem. This phenomenon is especially apparent

when an extremity is amputated by the detonation

of a buried antipersonnel mine. Much of the damage is done by penetrating missiles that arise secondarily from the ground, the soldier’s boot, and

even his foot. The secondary missiles, in conjunction with the “blast wind” (ie, the mass of air displaced by the explosion) are responsible for the

gross mutilation that is characteristic of such injuries. Primary blast injury—due to overpressure

from a blast wave—is distinctly uncommon in surviving casualties except in the form of perforated

tympanic membranes. It is possible that, in future

wars, the development of enhanced blast weapons

such as fuel air explosives will increase the possibility of more-serious blast overpressure injuries involving the lung and solid abdominal viscera.23

Blunt trauma, the mechanism of injury responsible for most civilian trauma, is much less common

as a cause of battle injury. When combat blunt

trauma is found, it is usually in the context of a

tactical vehicle detonating an antitank mine.24 Even

in these circumstances, blunt injury is the cause of

only a small proportion (8%) of tank-crew casualties.25

The infrequent use of flame and incendiary weapons in modern warfare would be expected to make

thermal injury uncommon. When soldiers are

burned, the thermal injuries are usually caused by

secondary explosions and fires arising from the fuel

of battle-damaged armored fighting vehicles and

aircraft. During World War II, about 40% of tankcrew casualties who survived to receive care were

burned.25 Half of these men had burns as their only

injury. The other half had burns in addition to

penetrating missile wounds. Most of the remaining

60% of tank-crew casualties had penetrating trauma.

The design of the armored vehicles used by the U.S.

military, such as the Abrams main battle tank, has

minimized the potential for secondary explosions

and fires, further decreasing the likelihood for thermal injury.
Anesthesia and Perioperative Care of the Combat Casualty

8

Unique circumstances, however, may generate

large numbers of burned casualties. For example, at

least 14% of all British army casualties in the

Falklands War sustained burns because of a single

combat action: two British troopships were set on

fire by enemy action before the soldiers could disembark.26

Nonbattle Injury

The preceding treatment of mechanisms deals

exclusively with injuries sustained as the result of

the hostile actions of a military enemy. There is

another category of trauma that may afflict soldiers

in the combat zone: nonbattle injury. Nonbattle

injuries show some similarity to civilian trauma in

that blunt and thermal trauma are common. Vehicular accidents, especially those involving rotorwing aircraft, are common, but most serious cases

of nonbattle injury result from accidents with weapons such as explosive munitions. Thus, penetrating

missile wounds are also commonly found in soldiers with nonbattle injuries.

The lethality of nonbattle injuries in the Vietnam

War can be calculated: dead at the site of the accident, 5.0%; died in hospital, 1.2%.27 As will be

discussed later in this chapter, the mortality of

nonbattle injuries is significantly lower than the

mortality of battle injuries.

Service-Specific Aspects of Combat Injury

The mechanisms of injury and the rates of attrition are service-specific. During World War II, the

overall U.S. Navy casualty rate was about 0.06% per

day.28 The probability of a fatal outcome following

a combat injury on a ship was much higher than that

observed in conventional land warfare: 48% of casualties were either killed or missing. Penetrating

injuries were found in 39% of surviving naval casualties; this mechanism of action is therefore much

less common aboard ship than in land warfare.

Burns were the mechanism of injury in 22% of the

casualties. Combined penetrating and thermal

trauma occurred in 11% of casualties.

As befits the nature of air warfare in the last half

of the 20th century, aircrew (air force and navy)

casualties are uncommon, and their medical outcome is closely related to the magnitude of the

aircraft’s battle damage. When the damage is sufficiently severe to cause the loss of the aircraft, about

two thirds of the crew can be expected to become

casualties. Data indicate that one half of airmen

who are injured are killed, and about two thirds of

survivors have orthopedic injuries due to blunt

trauma.29

Sources of Penetrating Missiles

Bullets from small arms and fragments from explosive munitions are the two sources of penetrating wounds on the modern battlefield. In the major

wars of this century, wounds made by explosive

munitions have been numerically much more important, being found in more than two thirds of all

casualties. Three examples illustrate this statement. One study of British casualties in Normandy

found that 69% of the casualties had wounds made

by explosive munitions.9 Similarly, in the Israeli

army in the Lebanon War of 1982, explosive munitions caused about 80% of the casualties.30 The U.S.

experience in the Vietnam War was no different:

about 76% of all army casualties had penetrating

missile wounds caused by fragments from explosive munitions.16 However, an analysis of the Vietnam data provides this interesting insight: the relative numerical importance of bullet and fragments

as the sources of penetrating wounds depends on

how the war is fought. In the early part of the war,

the percentage of soldiers with gunshot wounds

was unusually high, sometimes exceeding 50%. The

reason is that during the early part of the Vietnam

War, U.S. Army units engaged in search-and-destroy operations in which both they and their opponents were usually armed with small arms.22 A high

proportion of casualties with gunshot wounds is

one characteristic of low-intensity warfare, unlike

what is found in high-intensity warfare involving

armored fighting vehicles, artillery, and aircraft.

Explosive Munitions

The explosive munitions that cause fragmentation injuries are shells, rockets, bombs, mortars,

mines, hand grenades, and ad hoc devices such as

booby traps.31 The basic design consists of a container, a fuze, and an explosive. Until recently, the

container (ie, the shell), being broken apart by the

detonation of the explosive, provided the fragments.

Because the shell broke into irregular pieces of

assorted sizes (some weighing a pound or more)

and a range of velocities, it is customary to refer to

such weapons as “random”-fragmentation munitions. With explosive munitions of more recent

vintage, the container is designed to break up into

small pieces of uniform size and shape; therefore,

the fragments’ initial velocities are constrained to a

narrow range. A typical design produces hundreds
9

Combat Trauma Overview

to thousands of 50- to 1,000-mg fragments, which

are expelled with very high initial velocities (4,000–

6,000 fps). In the most modern designs, preformed

fragments are placed in the container and are expelled by the detonation of an explosive charge.

The Vietnam War–era Claymore mine, with its 700

steel ball bearings (0.75 g each), is a good example of

an explosive munitions containing preformed fragments. In the armaments industry, the two latter

categories of explosive munitions are referred to as

“improved”-fragmentation munitions.

The penetrating wounds produced by randomand improved-fragmentation munitions show characteristic differences. The older explosive munitions, especially the shells, were capable of causing

massive mutilating injuries such as decapitation.

Improved-fragmentation munitions characteristically produce multiple wounds; frequently,

the casualty will be riddled with many small fragments.

Another characteristic of modern explosive munition design is that the individual munitions are

frequently clustered (ie, packaged together) in a

carrier (a bomb, shell, or rocket) for delivery to the

enemy position. The individual submunitions are

disseminated from their carrier before being detonated. Such cluster munitions greatly increase the

casualty-generating potential of a given weight of

munition.

A recently developed cluster munition consists

of shaped-charge warheads with easily fragmentable

side walls. A shaped-charge warhead is a sophisticated device that was developed during World War

II as an antiarmor weapon. The hot, rapidly moving

gas produced by the explosion of the shaped-charge

warhead is focused in much the same way that a

lens focuses light. By combining the antiarmor

effect of the shaped-charge warhead with antipersonnel fragmentation effects, a dual-purpose

submunition can be made.

Small Arms

The most commonly used military small arms are

the assault rifle and the machine gun.31 Their essential characteristic is that they are fully automatic;

that is, they will fire as long as the trigger is pulled

and there are rounds in the magazine. This behavior distinguishes military from civilian small arms:

the latter class of weapons, although usually but

mistakenly referred to as “automatic,” are actually

“semiautomatic.” In a semiautomatic small arm,

the trigger must be pulled every time a bullet is

fired. What is automatic in a semiautomatic small

arm is the chambering (of rounds) and extraction

(of cartridges).

The machine gun was perfected during World

War I to the extent that it displaced the single-shot,

bolt-action rifle as the dominant military small arm.

The machine gun was responsible for some of the

most notorious slaughters on the western front,

including the killing of some 20,000 British soldiers

on the first day of the Battle of the Somme in 1916.32

The assault rifle was developed during the last

years of World War II and may be looked on as an

effort to give the individual soldier some of the

potential firepower of the machine gun. The two

best-known assault rifles today are the M16 series

developed in the United States (the M16A2 is not

technically fully automatic, as it is designed to fire

three-round bursts) and the various designs of

Kalashnikov such as the AK47 and the AK74.

The most commonly used machine gun and assault rifle bullets have calibers (in millimeters) of

5.45, 5.56, 7.62, and 12.7. The muzzle velocities

range between 2,350 and 3,300 fps. Such velocities

are substantially greater than those found in bullets

fired by civilian handguns, which typically have

muzzle velocities of 800 to 1,200 fps. Because the

kinetic energy of a projectile is a function of its

velocity squared, bullets fired from military small

arms almost always have muzzle kinetic energy

substantially greater (3-fold or more) than that of

bullets fired by civilian handguns.

The potential for massive energy transfer and

resultant tissue damage is increased by the high

kinetic energy of military bullets. Whether the

potential is actually realized, however, depends on

aspects of the bullet’s construction and the biophysical characteristics of the target tissue. The

latter factor is apparent when comparing wounds

made in bone and lung. Energy transfer is maximized when a missile strikes bone, but is minimized

in lung with its low density and high viscoelasticity.

A bullet’s construction becomes an important determinant of energy transfer when it potentiates

deformation or fragmentation. Bullets fired by military small arms are required by international law to

be covered by a metal jacket, which is supposed to

minimize deformation. Consequently, deformation of military bullets is less commonly seen than

with unjacketed bullets used by civilians. Nevertheless, military bullets can cause extensive tissue

damage because they may break up or fragment

along their trajectory in the body. The fragmentation occurs because the bullet’s metal jacket can

easily be disrupted. Fragmentation is commonly

seen with the M193 and M855 rounds fired by the
Anesthesia and Perioperative Care of the Combat Casualty

10

M16 series of assault rifles, but also occurs with

7.62-mm x 51-mm North Atlantic Treaty Organization (NATO) and M1943 Kalashnikov rounds, when

manufactured with thinner-than-usual or nonsteel

jackets, respectively.

Another factor that tends to increase energy transfer from military small-arm bullets is their propensity to yaw and tumble in tissue. This instability is

more common than with bullets designed to be

fired from civilian handguns, and is caused by the

characteristic long, pointed shape of military bullets, which, by maximizing the separation between

the bullet’s centers of pressure and mass, predisposes to yaw and tumbling.

Massive energy transfer usually results in massive tissue damage. Nevertheless, it is important to

recognize that neither the magnitude of the energy

transfer nor the magnitude of tissue damage is

necessarily synonymous with the magnitude of the

medical treatment problem. A tiny wound of the

parietal cortex made by a small fragment with several hundred joules of energy gives rise to a far

different medical problem than does a massive

above-the-knee amputation caused by the transfer

of tens of thousands of joules of energy from an

exploding antipersonnel mine.

The lethality of penetrating missile wounds sustained in combat is well defined.30 The probability

of a fatal outcome from a fragment wound made by

a random-fragmentation munition is about 1 in 5 for

shells and about 1 in 10 for hand grenades. Paradoxically, the lethality of improved-fragmentation

munitions is lower: 1 in 7 for shells and as low as 1

in 20 for hand grenades. The probability of a fatal

outcome from a single wound made at random by a

bullet from a military small arm is about 1 in 3. Due

to the fully automatic design of military small arms,

multiple wounds can be expected; in fact, data from

the Vietnam War show that a soldier killed by

military small-arms fire was struck, on average, by

3.2 bullets.15

Distribution of Missile Wounds by Body Surface

An understanding of the medical treatment problems caused by bullets and fragments is furthered

by understanding the distribution of penetrating

missile wounds on the body surface. Unfortunately,

data from previous wars giving the distribution of

wounds are difficult to interpret for several reasons:

• First, the definitions of body regions lack

consistency (eg, where does the shoulder

become the thorax?).

• Second, diverse selection criteria are used

(eg, some reports deal only with treated

casualties, while others include dead as well

as living casualties).

• Third, many casualties have wounds that

involve multiple regions on the body. How

to classify such casualties is a major methodological problem.

It is possible to simplify the analysis of the distribution of penetrating missile wounds by assuming

that, to a first approximation, hits on the body are

random and thus are distributed as a function of

body surface area (eg, a thigh gets more hits than a

little toe because it has more surface area). If

so, then the observed distribution should be approximated by the “Rule of Nines” (Table 1-3, first

column).

Of course, most soldiers are not wounded while

standing in the anatomical position, so using the

Rule of Nines for estimating regional body surface

areas is not likely to make for accurate predictions.

During World War II, British analysts attempted to

develop a model for the observed distribution of

wounds by assuming that the exposed body surface

area was very much altered by the position of the

soldier at the time of wounding.33 For example, the

regional distribution of the surface area exposed to

a frontal attack is very much different for a soldier

crouching or in the prone position, compared with

one standing in the anatomical position (see Table

1-3, second column).

Although the problem of multiple wounds is not

addressed, the most useful treatment of the distribution of penetrating missile wounds is Beebe and

DeBakey’s analysis of the World War II data of the

U.S. Army.11 The distribution observed in World

War II for the total population of casualties for

ground warfare (see Table 1-3, third column) shows

a major deviation from the predicted distribution in

the unexpectedly high proportion of head wounds.

Although the observed distribution represents the

effect of aimed fire to a limited extent, the increased

propensity of missiles to strike the head is primarily

due to the head’s increased exposure (for tactical

reasons) compared with other body parts. The

fourth column of Table 1-3 shows the distribution

observed for casualties who survived long enough

to enter the medical system. It also shows an unexpectedly high number of casualties with head

wounds, but the departure from the predicted distribution is less than that seen in the total casualty

population. No doubt the decrease in the percentage of casualties with head wounds who survive to
11

Combat Trauma Overview

TABLE 1-3

DISTRIBUTION OF MISSILE WOUNDS BY BODY SURFACE AREA (PERCENTAGE)

WWII2

Body Region Rule of Nines Predicted1 All Living

Head, Face, and Neck 9 12 21 15

Chest and Abdomen 37*

Chest 16 13 10

Abdomen 11 11.5 5

Extremity

Upper 18 22 23.5 28

Lower 36 39 35 41.5

* The combined surface areas of the torso plus the genitals and the perineum

Definitions:

Rule of Nines: body surface area as used to quantitate the magnitude of a burn

Predicted: the standard anatomical distribution of regional surface areas has been adjusted by assuming that the soldier will be in

a variety of combat-relevant postures (standing, crouching, and prone), weighted according to an assumed probablity

WWII: All: US Army ground casualties, both living and dead

Living: US Army ground casualties who survive to enter the medical system

Data sources: (1) Palmer A. Survey of battle casualties, Eighth Air Force, June, July, and August 1944. In: Beyer JC, ed. Wound Ballistics.

Washington, DC: Department of the Army, Office of The Surgeon General; 1962: 573. (2) Beebe GW, DeBakey ME. Battle Casualties.

Springfield, Ill: Charles C Thomas; 1952: 92, 186.

receive treatment is indicative of the high immediate lethality of such wounds.

The data in Table 1-3 are consistent with the

conclusion that the regional distribution of penetrating missile wounds is an approximate function

of the distribution of body surface area except that

the head, face, and neck receive about twice as

many wounds as expected. The discrepancy is

lessened when adjustments are made for the position assumed by the soldier during combat and

when only treatable casualties are considered. Either way, about two thirds of all casualties can be

expected to have wounds of the extremities.

Wound Depth

The data in Table 1-3 give only the location on the

body surface of a penetrating wound and do not tell

whether there is an associated internal injury. Both

a superficial wound involving only the abdominal

wall and a wound made by a missile that perforates

through the entire abdomen and injures several

intraabdominal viscera are classified as abdominal,

but only the latter wound is likely to be associated

with mortality or significant morbidity. Thus, regional wound distributions need to be interpreted

in terms of the depth of the wound tract. A therapeutically useful distinction can be made between

penetrating missile wounds that involve only soft

tissue (ie, skin, fat, or skeletal muscle) and those

that also involve bone, neurovascular structures, or

viscera. The distinction between soft-tissue and

visceral wounds can also be applied to resolving the

problem of classifying casualties with multiple

wounds because many have multiple soft-tissue

wounds only, or have, in addition to the soft-tissue

wounds, an injury of a solitary internal organ. The

classification of penetrating wounds in this chapter

uses the distinction between soft-tissue and visceral

wounds and utilizes two resources: the Wound

Data and Munitions Effectiveness Team (WDMET)

study15 from the Vietnam War and the Abbreviated

Injury Scale (AIS)34 developed by the Association

for the Advancement of Automotive Medicine.

The WDMET study consists of detailed descriptions of about 8,000 U.S. Army and U.S. Marine casualties wounded during an 18-month period from 1967

to 1969. Teams of data collectors accompanied company- and battalion-sized units during tactical operations such as search-and-destroy missions. Data were

collected on the tactical situation, the weapons that

caused the wounds, field first aid and the circumstances of evacuation, the detailed anatomy of

wounds (including autopsy reports for those who

were fatally wounded), and initial care in hospitals.

The WDMET study is uniquely valuable because an

effort was made to describe all casualties occurring

during a given combat action, including the killedin-action and carded-for-record-only categories, in

addition to casualties who were hospitalized.
Anesthesia and Perioperative Care of the Combat Casualty

12

The AIS was introduced in 1976 for the purpose

of standardizing the assessment of trauma resulting from automobile accidents. The potential lethality of a given injury was assigned a numerical

rating: 1 (minor), 2 (moderate), 3 (serious), 4 (severe), 5 (critical), and 6 (not survivable). Nine

anatomical regions were recognized: head, face,

neck, thorax, abdomen, spine, upper extremity,

lower extremity including the pelvis, and external.

The last region is the skin and superficial soft tissue.

Although the AIS initially emphasized blunt trauma,

subsequent modifications have included entries for

penetrating trauma.

Combat casualties from the WDMET database

were classified according to the AIS with these

exceptions: following the methodology used by the

Injury Severity Score (ISS), the pelvic bones were

considered part of the extremities, and the spine

was amalgamated into the neck, thorax, and abdomen anatomical regions.35 The following anatomical definitions were used:

• external, which includes skin, fat, and skeletal muscle anywhere on the body;

Head

4%

Superficial

47%

Multiple

5%

Extremity

26%

Abdomen

8% Chest

4%

Neck

2%

Face

4%

Fig. 1-5. Distribution of nonfatal (a) and fatal (b) wounds by body region. Superficial wounds (involving the skin, fat,

and skeletal muscle) and injuries to the bones of the extremities are the most common sites of nonfatal wounds. The

head and chest are the most common sites of fatal injuries. The multiple wounds category is restricted to casualties

whose injuries were (1) of equal value according to the Abbreviated Injury Scale and (2) to at least two different body

regions. Data source: Wound Data and Munitions Effectiveness Team database.

• head, which includes the skull and its contents;

• face, which includes the facial bones, eyes,

and the oral and nasal cavities;

• neck, which includes the viscera and the

cervical spine;

• chest, which includes the rib cage, thoracic

spine, and thoracic viscera;

• abdomen, which includes the abdomen, pelvis, and the lumbar spine; and

• extremity, which includes bones and

neurovascular structures.

It should be noted that the word “extremity” as

used in this analysis does not have the same meaning that it has in Table 1-3; in those data, not only

fractures and neurovascular injuries but also

wounds of the soft tissues are included in the term

“extremity.”

A casualty with two or more wounds was assigned to a specific body region rather than the

multiple category only if the AIS value for an injury in

one region exceeded the AIS values for all injuries in

the other regions. Only casualties who had two or

more injuries of equal AIS value in different body

a b

Superficial

1%

Head

38%

Face

4%

Neck

4%

Chest

24%

Abdomen

9%

Extremity

3%

Multiple

17%
13

Combat Trauma Overview

regions were classified as multiple. Thus, a casualty

with AIS injuries of 5 for both the brain and the lung

was classified as multiple, while a casualty with an

AIS injury of 4 in the liver and 3 for the extremity was

placed in the abdominal category. The analysis of

the WDMET data in terms of the AIS for casualties

who were fatally wounded and for those who survived is shown in Figure 1-5. About two thirds of

fatally wounded casualties had wounds of either the

head or the chest. Wounds of the soft tissues and the

extremity skeleton were found in about three fourths

of living casualties. This last finding is consistent

with the military surgery experience of the 20th

century, which is that at least two thirds of operations performed on combat casualties involved the

management of soft-tissue wounds and fractures.

0

10

20

30

40

50

60

70

80

90

100

General Hospitals

and CONUS

Surgical and

Evacuation Hospitals

First and Second

Echelons

Battlefield

World War II

Korean War

Vietnam War

Percentage of Total Combat Deaths

Fig. 1-6. The site of death for 90% of

fatally wounded combat casualties

is the battlefield. CONUS: continental United States. Data sources: (1)

Beebe GW, DeBakey ME. Battle Casualties. Springfield, Ill: Charles C

Thomas; 1952: 21, 92, 125, 186. (2)

Reister FA. Medical Statistics in World

War II. Washington, DC: Department

of the Army, Office of The Surgeon

General; 1975: 13; 90, Table 7; 202,

Table 17. (3) Reister FA. Battle Casualties and Medical Statistics: US Army

Experience in Korea. Washington, DC:

Department of the Army, The Surgeon General; 1973: 12, 17, 45.

MEDICAL OUTCOME OF COMBAT INJURY

The medical outcome of combat trauma is usually discussed in terms of mortality and morbidity.

Mortality is easily measured because it is not difficult to recognize when someone is dead. Much

more difficult is arriving at an all-embracing definition of morbidity. When is an injury present, and

how severe must it be to for the soldier to be classified as a casualty? These are not idle questions. One

of the major problems of interpreting combat casualty data from the Vietnam War is that in addition to

such casualty categories as killed in action, died of

wounds, and wounded in action, there is a fourth

category: carded for record only. Casualties who

are carded for record only have very minor wounds

that require either no treatment or treatment that

does not require admission to a medical treatment

facility. Should these soldiers be included in any

assessment of medical outcome? Inclusion of casualties who are carded for record only has a marked

effect on mortality and morbidity data because the

population is not numerically insignificant: they

constituted the largest single group of the U.S.

Army’s combat casualties in the Vietnam War. Such

casualties have been excluded from the following

analysis because their conditions do not constitute

medical problems.

Combat mortality is quantitated in terms of two

indicators: killed in action and died of wounds.1

They differ not only in terms of time of death but,

more importantly, in where death occurred. The

locations of death for fatally wounded U.S. soldiers

in World War II, the Korean War, and the Vietnam

War, combined, are shown in Figure 1-6.11,20,21 About

90% of fatally wounded U.S. soldiers expired on the

battlefield; only about 10% expired after having

entered the medical system. Expiring before entering the medical system is tantamount to dying before receiving effective medical care; in AMEDD,

this means dying before reaching the battalion aid

station, the lowest level at which a medical treatment facility is found. Thus, casualties who are

killed in action expire before reaching any medical

treatment facility, while casualties who die of

wounds expire after reaching a medical treatment

facility.

Mortality outcome data are given not only as the

gross number of casualties who are classified as

killed in action or died of wounds but also as nor-
Anesthesia and Perioperative Care of the Combat Casualty

14

malized statistics: as the percentage of the total

casualty population, or the percentage of the admitted/

hospitalized population (ie, casualties who were admitted to a medical treatment facility, the vast majority of whom were then hospitalized), respectively.

Killed in Action

The formula for calculating the percentage of

casualties classified as killed in action is

total number classified as killed in action

total number of casualties

The magnitude of the percentage of the population

who are killed in action depends on at least three

factors:

1. The lethality of the weapons. A war fought

with assault rifles is likely to have a greater

percentage of casualties who are killed in

action than a war fought with BB guns.

2. The feasibility and effectiveness of first aid.

3. The length of time required for evacuation

from the battlefield to a medical treatment

facility. The longer a casualty remains on

the battlefield, he is not only more likely to

die from his original wound but he is also

more likely to receive a new and possibly

more-lethal wound.

Exhibit 1-1 shows sample calculations of percentages of killed in action for the U.S. Army in the

Vietnam War.16 Depending on which data and

definitions are used, the percentages range between

14.6% and 24.2%. The higher figure is probably a

better indicator of the probability of a fatal outcome

when wounded by enemy action, because it excludes the casualties who are carded for record only

and includes all killed and missing soldiers.

Data from 604 soldiers recorded in the WDMET

study as having been killed in action suggest that

most fatally wounded casualties die very rapidly,

with perhaps 70% being apparently dead within 5

minutes of wounding (Figure 1-7). This observation has important implications for interpreting the

relation between mortality and the time for evacuation. One of the major criteria for judging the

effectiveness of the medical service in the field is the

time taken to evacuate casualties. During the Vietnam War, the time from wounding until a U.S.

Army casualty left the battlefield was unprecedentedly short (median time 29 min).15(T4-1-7) Because most casualty evacuation in Vietnam was by

helicopter and most evacuation flights lasted less

than half an hour (usually 5–20 min), it seems quite

likely that most casualties were received by hospitals within 1 hour of wounding. Nevertheless, this

evacuation time, which is so much faster than that

of any previous war (eg, in Italy in 1944, the average

time was 11.4 h from wounding to operation36), is

still not swift enough, when considered in the context of Figure 1-7, to save more than a tiny fraction

of fatally wounded casualties.

Died of Wounds

The formula for calculating the percentage of

casualties classified as died of wounds is

total number classified as died of wounds

• 100

total number of admitted or hospitalized casualties

The magnitude of the percentage of the population

who die of wounds depends on at least two factors:

1. Adequacy of surgical care. For example, if

no neurosurgical care can be given, the

number of casualties with head wounds

who die will increase.

2. Casualty load and triage considerations.

For example, during a mass casualty situation, it may be necessary to place certain

casualties in the expectant category, resulting in a greater number of casualties who

will die of wounds.

Exhibit 1-1 also shows sample calculations of

percentages of casualties who died of wounds for

the U.S. Army in the Vietnam War. Depending on

which data and definitions are used, the percentage

who died of wounds can be calculated to be 2.2%,

3.1%, or 3.4%. The first figure included the casualties who were carded for record only in the denominator and is invalid, since FM 8-55 states that the

died-of-wounds population is part of the woundedin-action population, but the carded-for-record-only

population is not.1 The population base for the 3.1%

figure includes only admitted/hospitalized casualties and is, therefore, a more valid indicator of

mortality in casualties who need medical treatment.

Hospital mortality (ie, excluding the casualties who

died while at the first or second echelons) was 3.4%.

The time of death for casualties who died of

wounds as found in the WDMET data is shown in

Figure 1-7. These data are similar to those of the

British experience in the Normandy campaign, in

which 50% of deaths occurred in the first 24 hours,

• 100
15

Combat Trauma Overview

EXHIBIT 1-1

KILLED IN ACTION AND DIED OF WOUNDS DURING THE VIETNAM WAR, 1961–1979

Dead:

1. Killed in action 27,129*

2. Died of wounds 3,529†

3. Died while missing in action 5,998‡

Wounded in Action (WIA) but Survived:

4. WIA, admitted to hospital 96,924

5. WIA, admitted to nonhospital medical treatment

facility, or quarters 13,716

6. Carded for record only 44,858

*Records of the Office of The Adjutant General (OTAG) state that there were 30,562 casualties classified as killed in action.

†104 casualties died at the first or second echelons (ie, before reaching a hospital).

‡Records of OTAG state that 5,998 soldiers were classified as died while missing; these casualties are in addition to those

killed in action. Most were probably killed in helicopters that were destroyed in combat actions.

Data source: The Office of The Surgeon General as collated in: US Army Patient Administration Systems and Biostatistics

Activity. Battle Injury Dispositions by Causative Agent—Active Duty Army Personnel with Initial Admission in Vietnam.

Fort Sam Houston, Tex: Academy of Health Sciences, Department of the Army: 2 June 1981. Unpublished data.

Sample Calculations

(The numerals on the left side of the equation refer to the categories shown above)

Percentage Killed in Action:

14.6: Defined as number classified as killed in action divided by the total number of casualties exclusive of

the missing: categories 1÷(1+2+4+5+6) = (27,129÷186,156) • 100

17.2: Defined as number classified as killed in action plus died while missing divided by total number of

casualties: categories (1+3)÷(1+2+3+4+5+6) = (33,127÷192,154) • 100

18.6: Defined as number classified as killed in action according to OTAG plus died while missing divided by

total number of casualties: categories (1+3)÷(1+2+3+4+5+6) = (36,460÷195,587) • 100

24.2: Defined as number classified as killed in action according to OTAG plus died while missing divided by

total number of casualties minus the carded for record only: categories (1+3)÷(1+2+3+4+5) = (36,460÷

150,729) • 100

Percentage Died of Wounds:

2.2: Defined as number classified as died of wounds divided by total number of casualties minus killed and

missing: categories 2÷(2+4+5+6) = (3,529÷159,027) • 100

3.1: Defined as number classified as died of wounds divided by total number of casualties admitted to hospital,

nonhospital medical treatment facility, and placed on quarters: categories 2÷(2+4+5) = 3,529÷114,169 • 100

3.4: Defined as number classified as died of wounds minus 104 (number dead at first or second echelons)

divided by the total number of casualties admitted to hospital: categories 2÷(2+4) = (3,529 – 104)÷(100,453

– 104) • 100

80% within 3 days, and all but 5% by the end of the

first week.10 Because medical care can play an

important role in determining the outcome in casualties who are at risk of dying of wounds, the lethality associated with wounds of specific body regions

has changed during wars in which the U.S. Army

has been involved. During World War I, casualties

with wounds of the extremities who developed

anaerobic infection were the largest component of

the died-of-wounds category.11 During World War
Anesthesia and Perioperative Care of the Combat Casualty

16

45

40

35

30

25

20

15

0

10

5

1 d

to < 1 wk

5 to 30 min to < 2 h

< 30 min

Immediate < 5 min

Percentage of Total Combat Deaths

Killed in Action

Died of Wounds

Fig. 1-7. When the time to death after wounding is plotted for battlefield casualties who are killed in action and who

die of wounds, most are seen to die in less than 10 minutes, demonstrating that the “Golden Hour” seen in civilian

casualties does not apply. Data source: Wound Data and Munitions Effectiveness Team database.

II, the major cause of death in soldiers who died of

their wounds was intraabdominal injury.37 During

the Vietnam War, soldiers who died from wounds

of the head constituted the largest component of the

died-of-wounds category.38

This last fact has important implications for understanding the reciprocal relation between the

killed-in-action and died-of-wounds categories. It

is likely that rapid evacuation of gravely wounded

casualties from the Vietnam battlefield brought casualties to the hospital level who, in prior wars, would

have expired on the battlefield (and thus would

have been classified as killed in action). Thus, the

percentage of casualties who were killed in action

would be reduced, while the percentage of casualties who died of their wounds would be elevated.

The converse will be true given prolonged evacuation from the battlefield: the great majority of the

gravely wounded will die on the battlefield (and

will thus be classified as killed in action). Relatively

few will reach the hospital level, so the percentage

of casualties who died of wounds will be strikingly

low. This situation—a high percentage of casualties

who were killed in action (31%) and a low percentage of casualties who died of wounds (1.1%)—

characterized the British army’s Falklands War experience, a war in which evacuation time may have

been unusually long.26

In the past, the quality of medical care has all too

often been assessed in terms of the died-of-wounds

rate. However, this assessment may give very misleading results. The reciprocal relation between the

number of soldiers who are killed in action and the

number who die of wounds is shown schematically

in Figure 1-8, in which two hypothetical scenarios

with identical casualty populations are contrasted:

one in which evacuation is sluggish and hospital

care is mediocre, and one in which evacuation is

quite prompt and hospital care is optimal. Because

the died-of-wounds rate is higher in the second

scenario, it is possible to conclude that the quality of

care is worse. The correct conclusion becomes apparent only if the overall mortality is considered.

Then it is obvious that the care given in the first

scenario is inferior. The effectiveness of the entire

field medical system is measured when overall

mortality is studied.

Absence of a “Golden Hour” in Combat Trauma

Since D. D. Trunkey’s report39 on civilian trauma

was published in 1983, it has become customary to

assume that the times at which fatally injured trauma

victims die fall into three distinct periods: immediate

(within the first hour), early (2–3 h after injury), and

late (several days to several weeks after injury).

Trunkey’s study showed that about half of all deaths

occur in the immediate period, 30% in the early, and

the remainder in the late. Based on this distribution, there is reason to believe that, given rapid

evacuation to a trauma center and excellent care

there, many of the deaths that occur in the early

period can be prevented. The first hour after injury

has been called the “Golden Hour,” since care insti2 to < 6 h 6 h ≥ 1 wk

to < 1 d
17

Combat Trauma Overview

 

 

Fig. 1-8. These two hypothetical populations of combat casualties with identical Injury Severity Scores are evacuated

at different speeds and receive different medical care. The difference in medical outcome appears paradoxical: the number

of casualties who die of wounds is much higher in the rapidly evacuated group, although the total mortality is lower.

tuted within this interval is likely to be lifesaving

for trauma victims who might otherwise die in the

early period. Care started after the first hour is

more likely to be futile. A similar, albeit less wellsubstantiated and -defined concept, is found in

combat casualty care: the medical service has an

hour to institute lifesaving first aid in the critically

wounded soldier; otherwise, survival becomes increasingly unlikely.

The clinical evidence that was used to establish

the trimodal distribution of trauma deaths is of

civilian origin and, therefore, blunt trauma was the

usual mechanism of injury. However, Figure 1-7

shows no evidence of a trimodal distribution of

combat deaths: 80% to 90% of all deaths occur during what, by analogy, would be Trunkey’s immediate period, with perhaps 70% occurring in the first

5 minutes. Although there are late deaths, it is

difficult to recognize a distinct cluster of deaths

after the initial peak. It is likely that this difference

between the military and civilian experiences arises

from the great predominance of penetrating trauma

in the former, with penetrating injury’s potential

for rapid exsanguinating hemorrhage. Support for

this view comes from a 1993 study40 of a civilian

trauma population who had a much higher percentage of penetrating trauma than the population in

Trunkey’s study. Most deaths in the 1993 study

occurred during what would be Trunkey’s immediate period, following which deaths became progressively less common until the onset of sepsis and

multiple organ failure days afterward. The implication for combat casualty care, based on the observed distribution of deaths found in the WDMET

data, is obvious: if there is a “golden” period, it is a

golden 5 minutes.

Historical Trends in Combat Mortality

Historical trends in combat mortality and their

supporting data are shown in Figure 1-9. The wars

have been selected for illustrative purposes and do

not constitute a systemic appraisal of combat mortality. As a general rule, at present, given optimal

combat casualty care, 20% to 25% of battle casualties can be expected to be killed in action and 3% to

5% of survivors reaching the hospital level alive

will die of their wounds. This conclusion depends

on two important qualifications: (1) medical care

must be state of the art and science and (2) the

tactical situation must allow for application of the

available medical resources. The latter qualification means that the army in question must not be

losing badly. Losers may have terrible combat

mortality. Two 20th-century battles illustrate this

point: at the battle of Stalingrad, about 75% of

German casualties were in the killed and died categories after mid-December 194241; at the battle of

Slow Evacuation, Suboptimal Care

1,000

Rapid Evacuation, Optimal Care

1,000

200

Immediate

battlefield

deaths

50

Gravely wounded,

late battlefield deaths,

or deaths during

evacuation

750

Reach hospital

alive

200

Immediate

battlefield

deaths

50

Gravely wounded,

who die during evacuation

or shortly after reaching

hospital

750

Reach hospital

alive

3.5% Die

of wounds

50% Die

of wounds

2% Die

of wounds

200 50 26 200 25 15

Total Mortality 24%

5% Died of Wounds

Total Mortality 27.6%

3.5% Died of Wounds
Anesthesia and Perioperative Care of the Combat Casualty

18

40

35

30

25

20

15

10

5

0

Percentage Killed or Died

1979–

1989

1970–

1984

1964–

1973

1950–

1953

1944–

1945

1914– 1940 1942

1918

1904–

1905

1870–

1871

1861–

1865

1854–

1855

Died

Killed

Dates of Selected Wars

Head Wounds

477

Multiple Injuries

107

Primary Injury

370

Killed

82 (d)

Died

32 (b)

Survived

84 (c)

Died

5 (e)

Killed

254 (a)

Hospitalized

25

Hospitalized

116

Survived

20 (f)

Fig. 1-9. See legend on page 19.

Okinawa, Japanese mortality was about 95% of all

soldiers.42 If there is one lesson that military history

teaches, it is that the essential prerequisite for low

combat mortality is to win!

Outcome of Specific Body-Region Injuries

The mortality of combat injuries can be understood best when wounds of separate body regions

are studied. The following outcome data are from

the WDMET study for soldiers wounded in the

head, chest, abdomen, and extremities.15 Casualties

were placed in the head category when a projectile

(bullet or fragment) reached the periosteum of the

skull or deeper; in the chest category when a projectile reached the rib cage or deeper; in the abdominal

category when a projectile perforated the peritoneum; and in the extremity category when a projectile injured the skeleton or a neurovascular structure in the upper or lower extremity. Injuries were

classified as primary (ie, one body region had an AIS

score greater than any other body region) or multiple (ie, two or more body regions had injuries of

equal potential lethality according to the AIS). Casualty outcomes were defined as follows:

• killed: succumbed on the battlefield,

• died: succumbed while receiving care at a

medical facility,

• hospitalized: admitted to a medical treatment facility, and

• survived: either returned to duty or was

alive when evacuated from Vietnam.

Head

• Total mortality: 373⁄477 = 78%

• Hospital mortality: 37⁄141 = 26%

Primary Injury. Of the 254 casualties whose

head wounds were their primary injury and who

were killed (point a on the diagram), 184 (72.4%)

sustained massive brain destruction (eg, injury to

three or more lobes, avulsion of the brain, decapitation, crushing of the head), and 43 (17%) had isolated injury to the midbrain or brainstem. The

remainder had an injury involving one or two lobes

or a depressed skull fracture.

Of the 32 who died after being hospitalized (point

b on the diagram), slightly fewer than one half were

treated expectantly.

Of the 84 casualties who survived (point c on the

diagram), 44 had an injury that involved only one

cerebral lobe, 15 had injuries involving two lobes,

and 12 had depressed skull fractures caused by

tangential gunshot wounds.

Multiple Injuries. Of the 82 casualties with multiple injuries who were killed (point d on the diagram), 27 (33%) had massive brain destruction in

addition to grossly mutilating injuries to other parts

of the body. Most of the remainder had injuries to

one or two lobes.
19

Combat Trauma Overview

Fig. 1-9. Percentages of casualties who died or were killed in selected wars. The figure is based on the following

supporting data:

1854–1855: British battle casualties in the Crimean War. Killed: 1,933; died: 1,5991; wounded: 12,100.2 The high hospital

mortality is characteristic of the preantisepsis era of military surgery. An additional 11,477 died of disease.

1861–1865: Union battle casualties in the American Civil War. Killed: 67,058; died: 43,012; wounded: 318,187.3 An

additional 233,789 died of disease. The killed figure does not include the missing in action, a significant

proportion of which probably were also killed.

1870–1871: German battle casualties in the Franco–Prussian War. Killed: 17,300; died: 11,000; wounded: 96,200.4

1904–1905: Japanese battle casualties in the Russo–Japanese War. Killed: 47,500; died: 11,500; wounded: 173,400.4

The first “modern” war in several senses: machine guns and high-explosive shells dominated the battlefield, and

some military surgeons used antiseptic and aseptic techniques.

1914–1918: British battle casualties in France and Flanders. Killed: 381,261; died: 151,356; surviving wounded:

1,837,613; missing and assumed killed: 144,890.5

1940: German battle casualties during the conquest of France, May–June 1940. Killed: 21.9%; died: 7.8%.6 Actual

numerical data are not given, but according to Fischer7 there were approximately 48,000 battle fatalities. The Germans

ascribed the high mortality to the delayed evacuation of casualties from rapidly moving armored units.

1942: German battle casualties on the Russian front, January 1942. Killed: 24.4%; died: 12.3%.6 Actual numerical data

are not given, but the same source indicates that there were about 55,000 battle fatalities.6 The high mortality is

the result of the extraordinary difficulty of providing effective combat casualty care in the extreme cold during

the massive Soviet counterattack that followed the collapse of the German attack on Moscow.

1944–1945: American battle casualties in Italy, January 1944–May 1945. Killed: 25,183; died: 2,770; total admissions

(carded for record only category excluded): 76,351.8 Reister’s data are somewhat different from those given by

Snyder and Culbertson9: killed: 16,648; hospitalized/died: 1,631; hospitalized/survived: 61,393; killed: 20.9%; died:

2.6%. The latter data do not include casualties who died of wounds prior to hospitalization nor some 9,000 additional

soldiers who were killed but were presumably still classified as missing when the data were collated in 1945.

1950–1953: American battle casualties during the Korean War.

10

1964–1973: US Marine Corps battle casualties during the Vietnam War. Killed: 11,490; died: 1,454; nonfatal wounds/

hospital care required: 51,399.11 The Marine Corps’ mortality data appear to be more favorable than are the

corresponding US Army data.

1970–1984: British army casualties from Northern Ireland, for soldiers killed or wounded by explosive devices.

Killed: 174; died: 42; total injured: 828.12 These data are useful for understanding mortality in “peacekeeping”

operations (now officially known as operations other than war [OOTW]). Evacuation time from the site of

wounding to surgical care was almost certainly shorter than that in any of the wars described. It is also probable

that the wounds were, on average, more severe.

1979–1989: Russian battle casualties during the Afghanistan War. Two sources are available. The first13 gives

normalized statistics for killed (19.5%) and died (3.5%), but actual data are given for what may be different

casualty categories: fatally wounded, 13,833, and wounded, 49,985. The second14 has the following entries:

killed: 9,511; died: 2,386; surviving wounded: 51,367. Using these data, killed in action would be 15.0% and died

of wounds 4.4%. Which source is correct is not known. Both sources indicate that there were more than 400,000

admissions for disease.

Data sources: (1) Palmer A. The Crimean War. New York, NY: Dorset Press; 1987: 244. (2) Beebe GW, DeBakey ME. Battle Casualties. Springfield,

Ill: Charles C Thomas; 1952: 77. (3) Livermore TL. Number & Losses in the Civil War in America: 1861–65. New York, NY: Kraus Reprint Co; 1969:

8. (4) La Garde LA. Gunshot Injuries. New York, NY: Wm Wood and Co; 1916: 413. (5) Mitchell TJ, Smith GM. Casualties and Medical Statistics

of the Great War. London, England: The Army Medical Services. His Majesty’s Stationery Office; 1931: 108. (6) Mueller-Hillebrand B. Statistics

System. US Army Historical Division Study PC 011 Koenigstein Ts. 1949: 121, 136. Unpublished. Available at the National Archives,

Washington, DC. (7) Fischer H. Der Deutsche Sanitätsdienst 1921–1945. Vol 2. Osnabrück, Germany: Biblio Verlag; 1983: 343. (8) Reister FA.

Medical Statistics in World War II. Washington, DC: Department of the Army, Office of The Surgeon General; 1975: 76–79. (9) Snyder HE,

Culbertson JW. Studies of Fifth US Army hospitalized casualty deaths. In: Beyer JC, ed. Wound Ballistics. Washington, DC: Department of the

Army, Medical Department, Office of The Surgeon General; 1962: 473. (10) Reister FA. Battle Casualties and Medical Statistics: US Army

Experience in Korea. Washington, DC: Department of the Army, The Surgeon General; 1973: 45. (11) Directorate for Information Operation and

Control. Number of casualties incurred by US military personnel in connection with the conflict in Vietnam. Washington, DC: Department

of Defense (OASD Comptroller), January 15, 1976: Table 1051. Unpublished. (12) Mellor SG, Cooper GJ. Analysis of 828 servicemen killed or

injured by explosion in Northern Ireland 1970–1984: The Hostile Action Casualty System.Br J Surg. 1989;76:1006–1011. (13) Nechaev E. Soviet

military experience in providing health care during Afghanistan War: Problems of further military medicine development. Military Medical

Journal (Moscow). 1992;2:5–14. (14) Krivosheyev GF, ed. Losses to the Armed Forces of the USSR in Battles, Combat Operations, and Military

Conflicts: Statistical Investigations. Moscow, Russia: Military Press; 1993: 402–404.
Anesthesia and Perioperative Care of the Combat Casualty

20

Of the 5 hospitalized casualties with multiple injuries who died (point e on the diagram), 2 were

treated expectantly. Of the 20 hospitalized casualties who survived (point f on the diagram), 7 had

single-lobe and 6 had double-lobe injuries.

In addition, the fatal head wounds of 7 casualties

who were killed in action were insufficiently described to justify inclusion in the diagram. An

additional 27 casualties, also not included, sustained systemic mutilation that almost certainly

included a fatal brain injury. Eight casualties with

gunshot wounds and 4 with fragment wounds of

the scalp did not have evidence of skull or central

nervous system (CNS) injury. They are not included, but one casualty with a gunshot wound of

the scalp and a cerebral concussion is included.

Type of Penetrating Missile. The partition by

outcome of casualties whose primary injury was in

the head by type of penetrating missile is as follows:

53% of those who were fatally wounded and 5% of

those who survived were injured by bullets; 28% of

those who were fatally wounded and 14% of those

who survived were injured by explosive munitions.

These data indicate that the probability of being

fatally wounded if struck in the head by a bullet

approached 9 in 10. In fact, of the casualties who

survived to be evacuated from Vietnam, only 3 in

the entire population (477) had penetrating head

wounds caused by a bullet in which the brain parenchyma was directly injured (as distinct from a depressed fracture of the skull with associated brain

injury caused by a tangential bullet wound). Casualties with multiple injuries of which one component was in the head were likely to be victims of

explosive munitions rather than small arms.

Chest

• Total mortality: 435⁄613 = 71%

• Hospital mortality: 30⁄208 = 14%

Primary Injury. Of 613 casualties who were

classified as having chest wounds, the chest wound

was the primary injury in 415. Of these, 260 were

killed (point a on the diagram). The sites of fatal

injury were heart or great vessels or both, 43%;

lung, including trachea, 30%; and heart, great vessels, and lung, 27%.

Of the 155 casualties who were hospitalized with

primary injury, 17 died (point b on the diagram): 8

deaths occurred intraoperatively, 7 died preoperatively, and 2 died postoperatively. Nine of these

casualties had wounds of the lung only, 4 had

wounds of the heart or great vessels, and 4 had

wounds of the heart or great vessels and lung.

Of the 138 casualties who survived their primary

injury (point c on the diagram), 61% had wounds of

the lung, 34% had a significant chest-wall injury in

addition to a lung injury, and 5% had a wound of the

mediastinum, which, in two cases, involved a partial-thickness laceration of the myocardium.

Multiple Injuries. Of the 198 casualties with

multiple injuries (but whose chest wounds were

predominant), 145 were killed (point d on the diagram). Of these, 53% had wounds involving the

lungs, 37% had mutilating wounds of the entire

trunk, and 10% had wounds of the lung and/or the

heart and the great vessels.

Of the 53 casualties with multiple injuries who

were hospitalized, 13 died (point e on the diagram).

Of these, 6 died before operation, 4 died intraoperatively, and 3 died postoperatively.

All of the 40 casualties who were hospitalized

and survived had wounds of the lung or chest wall

or both (point f on the diagram).

In addition, but not included in the diagram, 37

casualties had thoracic injuries in which the chest

component was of lesser severity when compared

to an injury in another body part. Of these casualties, 24 were killed, 4 died, and 9 survived. The

thoracic injury was limited to the lungs in 82% of

these casualties. An additional 18 casualties had

nonpenetrating injuries, but they also are not included here.

Of the 155 casualties who were evacuated alive

from the battlefield with primary thoracic injuries,

24 (15%) had a formal thoracotomy. Mortality in

this group was 10 of 24 (42%). Three casualties with

multiple injuries had a thoracotomy; all died.

Type of Penetrating Missile. The partition by

outcome of casualties whose primary injury was in
21

Combat Trauma Overview

the chest by type of penetrating missile is as follows: 44% of those who were fatally wounded and

11% of those who survived were injured by bullets;

30% of those who were fatally wounded and 15% of

those who survived were injured by explosive munitions. These data indicate that the probability of

being fatally wounded if struck in the chest by a

bullet is about 4 in 5. Most of the casualties in the

multiple category who had thoracic wounds were

injured by explosive munitions.

Abdomen

• Total mortality: 177⁄476 = 37% (42% when

casualties with negative laparotomies are

excluded)

• Hospital mortality: 39⁄338 = 11.5% (13.3%

when casualties with negative laparotomies

are excluded)

• Total mortality of casualties whose primary

injury involves the abdomen: 78⁄318 = 24.5%

(28% when casualties with negative laparotomies are excluded)

• Hospital mortality of casualties whose primary injury involves the abdomen: 25⁄265 =

9.4% (11% when casualties with negative

laparotomies are excluded)

Primary Injury. Of the 318 casualties whose

abdominal wounds were their primary injury, 53

were killed (point a on the diagram). In all casualties, death was due to hemorrhage: 42% exsanguinated from an intraabdominal vascular injury

(45%, iliac vessels; 40%, aorta or inferior vena cava;

15%, miscellaneous); 25% had a mutilating abdominal injury; 18% had involvement of multiple

intraabdominal organs exclusive of the named vessels; 11% had a liver injury; and 4% had an involvement of a single intraabdominal organ other than

the liver.

Of the 265 casualties who were hospitalized with

primary abdominal wounds, 25 died (point b on the

diagram). Death was due to hemorrhage in 60% of

casualties, intraabdominal sepsis in 25%, and pulmonary insufficiency in 15%. The sites of abdominal injury were as follows: multiple sites, exclusive

of vessels, 38% (average number of injured organs

was 4.4); intraabdominal vessels, 30% (the iliac vessels accounted for two thirds of these); liver, 21%;

single organ exclusive of the liver, 12%.

Two hundred forty casualties survived their primary abdominal wounds (point c on the diagram).

On average, survivors had 1.8 injured intraabdominal organs; one half of the survivors had an injury to

only one organ. The most commonly injured organs

were the colon including the rectum, 23%; the small

bowel including the duodenum, 23%; and the liver,

14%. Only 1% of survivors in the primary category

had a vascular injury.

Multiple Injuries. Of the casualties with abdominal wounds, 158 had multiple injuries. In this

category, 85 casualties were killed (point d on the

diagram). Of these, 71% had injuries to the chest;

about one half had true thoracoabdominal wounds

(ie, a single missile traversed both thorax and abdomen). The remaining casualties had various combinations of abdominal injuries in addition to wounds

of the head or extremities.

Of the 73 casualties with multiple injuries who

were hospitalized, 14 died (point e on the diagram).

All casualties in this category had wounds of the

lung in addition to their intraabdominal injuries.

Of the 59 hospitalized casualties who survived

(point f on the diagram), 65% had extremity wounds

in addition to their abdominal wounds; 25% had

head wounds, all but one of which were treated by

craniotomy; and 10% had chest wounds, one of

which required a thoracotomy.

There were an additional 7 casualties in whom

the abdominal component was of lesser severity

than a wound to some other body part. All 7 were

fatally wounded, and in all casualties the more

serious wound was to the head. An unknown

number of casualties had an injury that was subsequently shown to involve only the abdominal wall.

The number of such casualties approximates but is

greater than the number of casualties who had

negative laparotomies (39 casualties in the primary

category and 11 in the multiple categories, 15% of

all laparotomies). Casualties who had a negative

laparotomy were classified in the abdominal catSurvived

59 (f)

Died

14 (e)

Survived

240 (c)

Died

25 (b)

Hospitalized

73

Killed

85 (d)

Hospitalized

265

Killed

53 (a)

Multiple Injuries

158

Primary Injury

318

Abdominal Wounds

476
Anesthesia and Perioperative Care of the Combat Casualty

22

egory even though no intraabdominal injury was

present.

Type of Penetrating Missile. The partition by

outcome of casualties whose primary injury was in

the abdomen by the type of penetrating missile is as

follows: 24% of those who were fatally wounded and

10% of those who survived were injured by bullets;

19% of those who were fatally wounded and 47% of

those who survived were injured by explosive munitions. These data indicate that the probability of

being fatally wounded if struck in the abdomen by

a bullet was about 2 in 3. Most of the casualties in

the multiple category who had abdominal wounds

were injured by explosive munitions.

Extremities

Of the 721 hospitalized casualties, 717 survived

(point c on the diagram). About 50% of the survivors had fractures of extremity long bones, and 20%

had fractures involving the hands or feet. Major

extremity amputations and isolated vascular injuries were each found in 8% of the casualties in this

category.

Multiple Injuries. Of the 832 casualties with

extremity wounds, 55 were classified as having

multiple injuries; of these, 17 were killed (point d on

the diagram). Most casualties with multiple injuries exsanguinated from major extremity amputations or femoral artery lacerations, in addition to

hemorrhage from injured intraabdominal viscera.

The remainder had injuries to the head or thorax in

addition to the extremity wound.

Of the 55 multiply injured casualties in the extremity wound category, 38 were hospitalized, and

of these, 5 died (point e on the diagram). Casualties

in this category exsanguinated from femoral artery

injuries in conjunction with bleeding from within

the chest or abdomen.

Of the 38 hospitalized casualties with multiple

injuries, 33 survived (point f on the diagram). In

these casualties, the extremity injury coexisted with

injuries to the head (including the face), chest, and

abdomen, in that order.

Excluded from the extremity analysis were approximately 300 casualties in whom the extremity

injury was of secondary severity. Most of these

casualties fell into one of two categories: (1) grossly

mutilating injuries in which the extremity injury

coexisted with major disruption of the head or trunk,

and (2) a long-bone fracture in addition to a severe

and frequently fatal injury of the head, chest, or

abdomen.

Type of Penetrating Missile. The partition by

outcome of casualties whose primary injury was in

the extremity as a function of the type of penetrating missile is as follows: 4% of those who were

fatally wounded and 30% of those who survived

were injured by bullets; 11% of those who were

fatally wounded and 55% of those who survived

were injured by explosive munitions. These data

indicate that the probability of being fatally

wounded if struck in an extremity by a bullet that

injured bone or neurovascular structures was about

1 in 11. Explosive munitions were actually more

deadly than bullets: the probability of a fatal outcome was about 1 in 6. The reason for the higher

lethality of explosive munitions is no doubt related

to the propensity of antipersonnel mines to cause

amputations.

Primary Injury. Of 832 casualties classified with

extremity wounds, 777 had these wounds as their

primary injury. Of these casualties, 56 were killed

(point a on the diagram) and in all, the cause of

death was exsanguination. Thirty-five deaths were

caused by amputations of an arm or leg, 17

exsanguinated from an isolated arterial wound (the

femoral artery was the most common site), and 4

died who had sustained multiple extremity fractures.

Of the 777 casualties whose extremity wounds

were the primary injury, 721 were hospitalized. Of

these, 4 died (point b on the diagram). Two casualties died while being treated for femoral artery

lacerations, one died of gas gangrene following a

failed axillary artery repair, and one died in what

was reported as “mysterious circumstances” following treatment for a forearm amputation.

• Total mortality: 82⁄832 = 9.9%

• Hospital mortality: 9⁄759 = 1.2%

Extremity Wounds

832

Killed

56 (a)

Killed

17 (d)

Died

4 (b)

Died

5 (e)

Survived

33 (f)

Primary Injury

777

Multiple Injuries

55

Hospitalized

721

Hospitalized

38

Survived

717 (c)
23

Combat Trauma Overview

Morbidity

The ability of the medical service to perform its

mission, which is summarized in such statements as

“conserve fighting strength” and “maintain the fighting power of the command,” depends on how effectively combat morbidity is reduced. Morbidity is

more difficult to measure than mortality because

the latter has a clear endpoint. Indices of morbidity

that have been used are (1) the percentage of surviving wounded who return to duty, or alternatively,

the percentage of surviving wounded who are separated from the army, and (2) the length of time a

soldier who ultimately does return to duty remains

noneffective following a combat injury (Table 1-4).20–

22,43 The morbidity data for the U.S. Army have not

changed appreciably in the wars of this century. The

explanation is probably to be found in two facts:

• The rate of healing of bone and soft tissue

has not changed very much.

• The organization of the army in the theater of

operations, as well as other administrative

factors, does not allow rapid return to duty.

The latter observation may seem strange given

the official emphasis placed on conserving fighting

strength but was a well-known fact during both the

Vietnam War and the Persian Gulf War. During the

latter, there were many anecdotal reports that field

medical facilities were told to evacuate all casualties regardless of how soon they were expected to

return to duty. The reason for this decision is simply that extensive casualty-holding facilities within

the combat zone constitute a considerable logistical

burden. In a short conflict such as the Persian Gulf

War, in which there may be little need for replacements, it is neither necessary nor cost-effective to

hold wounded and sick soldiers in the combat zone.

What happened in Vietnam has a different explanation. Because there was a congressionally mandated limit on the number of troops within the

combat zone, senior commanders were faced with

the choice of either allowing the wounded to recover in country (and thereby reducing the number

of effective soldiers in combat units) or evacuating

the casualties from Vietnam and bringing in replacements, thereby maintaining the fighting strength. The

latter course was usually chosen, although commanders recognized that evacuated soldiers usually were

not returned to duty in Vietnam.

An army’s commitment to return to duty is implicit in its evacuation policy (ie, the maximum

number of days a casualty can be allowed to remain

in the theater of operation before he must be

evacuated).1(p4-1–4-3) For example, if the evacuation

policy is set at 30 days, a casualty judged by the

medical service to require more than 30 days to return

to duty would be evacuated as soon as possible. The

longer the evacuation policy, the greater the return to

duty from the theater of operation but, conversely,

the greater the medical deployment. Evacuation

policies have ranged from as long as 180 days in the

European Theater of Operations in 1944 to as short

as 7 days during one phase of the Persian Gulf War.

Soldiers with soft-tissue wounds and fractures

together constitute about three fourths of surviving

casualties (see Figure 1-5). Because soft-tissue

wounds heal much more quickly, on average, than

do fractures or complicated wounds of the trunk or

head, the population of casualties with soft-tissue

wounds makes a disproportionately small contribution to the total number of man-days lost. As a

general rule, about one third of the total man-days

lost are due to soft-tissue wounds, one third are due

to fractures, and one third are due to all other

wounds (but especially to complicated abdominal

or facial injuries).

The organization of the medical service in the

field can have an important impact on the magniTABLE 1-4

INDICES OF MORBIDITY

Days Disability Separation

War Noneffective (% of Wounded)

World War I1 96 11

World War II2 118 18

Korea3 93 9

Vietnam4 86* 11*

*No final figures appear to have been published for indices of

morbidity. Neel gives data that are specific for Vietnam, but

how long the soldiers who had been evacuated from there

remained noneffective is unclear. The figures given in this

table were obtained by extrapolation using factors derived

from the World War II and Korean War data given by Neel.

Data sources: (1) Love AG. Statistics. In: Medical and Casualty

Statistics. In: Medical Department of the United States Army in the

World War. Vol 15, Part 2. Washington, DC: Government Printing

Office; 1925: 1181, 1183. (2) Reister FA. Medical Statistics in World

War II. Washington, DC: Department of the Army, The Surgeon

General; 1975: 13. (3) Reister FA. Battle Casualties and Medical

Statistics: US Army Experience in Korea. Washington, DC: Department of the Army, Office of The Surgeon General; 1973: 712, 717. (4)

Neel S. Medical Support of the US Army in Vietnam 1965–1970.

Washington, DC: Department of the Army; 1973: 52–53.
Anesthesia and Perioperative Care of the Combat Casualty

24

Fig. 1-10. A highly simplified and idealized diagram of evacuation patterns used by the German Army in Russia in July

1941 and by the US Army in France in summer and fall, 1944. The red lines indicate the flow of casualties with

potentially fatal injuries; the green lines, the flow of casualties with nonlethal injuries. The German organization was

designed to evacuate to the corps and army levels all casualties whose injuries made return to duty within a few weeks

unlikely. Casualties with lesser injuries were retained within the division, where they were segregated to facilitate

rapid return to duty. The American organization was designed to evacuate the great majority of casualties, including

those with minor injuries, to the corps and army levels. Casualties with life-threatening injuries, however, received

resuscitative surgery before leaving the division. Thus, the American organization emphasized the saving of lives; the

German, the return to duty of the lightly wounded. Adapted with permission from Bellamy RF. Contrasts in combat

casualty care. Milit Med. 1985;150:406.

tude and duration of noneffectiveness of combat

casualties. Mortality can also be affected by the way

the medical services are organized. These conclusions are illustrated by comparing the U.S. and

German field medical organizations as they existed

during two discrete periods of World War II: the

German Army in Russia, summer 1941; and the U.S.

Army in France, summer 1944 (Figure 1-10).44

The German organization emphasized early return to duty by treating the less-seriously wounded

in the division area. To achieve this goal, a replacement company (Ersatz Kompanie) was attached to

the main medical unit organic to (ie, an intrinsic part

of) the division. Seriously wounded soldiers were

evacuated from the division to corps- and armylevel hospitals far to the rear.

The U.S. Army’s medical system was almost the

opposite in both casualty flow and goal. When

needed, a small surgical hospital derived from corps

assets was attached to the main medical unit organic to the division for the purpose of providing

resuscitative surgical care for the most-gravely

wounded soldiers. All other casualties, but especially those with less-severe injuries, were sent to

hospitals in the corps or army area, from where it

was difficult to effect a rapid return to duty.

As expected, the outcomes in terms of mortality

and return to duty for these contrary ways of organizing the medical system were very different (Figure 1-11). The German system sacrificed the seriously wounded (German died of wounds, 10.6%) at

the expense of soldiers who might be expected to

return to duty (German return to duty, 87%), while

the U.S. system strove to save lives (U.S. died of

wounds, 3.1%) but somewhat ignored the organizational aspects that would accelerate the return to

duty of the less severely injured (U.S. return to

duty, 70%). It should be understood that the twin

goals of saving lives and conserving fighting

strength are not necessarily incompatible.

Ersatz Kompanie 

General Hospital 

Verwundetennest Company Aid Post 

Truppenverbandplatz Battalion Aid Station 

Feldlazarett Field/Evacuation Hospital 

Field Hospital Platoon Hauptverbandplatz

Kriegslazarett

Surgical Team

German Army

Russia, 1941

U.S. Army

France, 1944 

Division Level 

Corps and Army Levels 

 FRONT 

Clearing Station 
25

Combat Trauma Overview

215

Killed in Action

24

Died of Wounds

212

Disability 

Separation

549

Returned 

to Duty

1,000

Combat Casualties

785

Treated

761

Survived

U.S. Army

(France, 1944)

236

Killed in Action

81

Died of Wounds

22

Unfit for

Military Service

262

Limited Duty

399

Fit for

Active Duty

764

Treated

683

Survived

661

Fit for

Military Service

1,000

Combat Casualties

German Army

(Russia, 1941)

Fig. 1-11. The numerical counterpart of the functional differences shown in Fig. 1-10. The German system returned to

duty a higher percentage of the surviving wounded than did the US Army but at the expense of a fatal outcome in

almost one third of the casualties. Adapted with permission from Bellamy RF. Contrasts in combat casualty care. Milit

Med. 1985;150:408.

Injury Severity Assessment

Approaches to injury severity assessment modeling fall into two categories: (1) those that measure

physiological parameters and (2) those that quantitate the anatomical damage. The best known and

most extensively used of the physiological injury

severity scoring systems is the Trauma Score, which

is calculated from measurements of respiratory rate,

respiratory effort, systolic blood pressure, capillary

refill, and the Glasgow coma scale.45 The range of the

Trauma Score is from 1 (dead) to 16 (normal). The

probability of survival is a function of the Trauma

Score; the ensuing curve has a sigmoid shape, with

scores of 8 or 9 predicting a 50% probability of survival. The desirable feature of the Trauma Score, as

with other physiologically based injury severity

systems, is that it is simple to apply and, therefore,

being readily repeatable, can easily demonstrate

changes in the casualty’s condition over time.

The purpose of the Trauma Score is to predict the

probability of death and, thereby, the desirability of

sending an injury victim to a trauma hospital. It

does this well when assessed in terms of predictive

power.46 However, the questions that need to be

asked in combat casualty care are not only “How

likely is the casualty to die?” but also “Is the casualty noneffective?” and “Does the casualty therefore need to be evacuated?” A casualty with a

penetrating missile wound of the abdomen, regardless of the actual Trauma Score, will require evacuation and laparotomy. A casualty with an open,

comminuted fracture of the femur may be physiologically intact but will certainly need to be evacuated from the battlefield. A physiological injury

severity index will not be helpful in making the

determination. Accordingly, the actual use of such

indicators of injury severity has been uncommon in

combat casualty care. Military anesthesiologists

interested in the important subject of the desirable
Anesthesia and Perioperative Care of the Combat Casualty

26

features of a militarily useful triage methodology

are referred elsewhere47 in the literature.

Anatomical injury severity models differ from

the physiological indices in this important respect:

physiological indices are battlefield useable, but

the anatomical indices are utterly useless for realtime application. The reason for this deficiency is

the near impossibility of obtaining the needed detailed description of the anatomical injury at the

time that triage and treatment decisions are made.

Nevertheless, the anatomical models, applied retrospectively, may permit useful insight into why

observed mortality and morbidity occurred.

The best known anatomical model is the Injury

Severity Score,48 which is, in essence, an algorithm

for combining Abbreviated Injury Scale entries for

different body regions. The major deficiencies of

this approach are well known: first, the Abbreviated Injury Scale was developed to assess, and is

most applicable to, blunt trauma; and second, the

Injury Severity Score ignores the cumulative effect

of multiple injuries within a given body region.

Nevertheless, the application of injury severity scoring to combat casualties should have some heuristic

value, in that the shape of the frequency distribution of injury severity may suggest how feasible it

really is to reduce combat mortality.

Theoretical Distribution

Many frequency distribution curves are theoretically possible. One possible curve is the standard

normal distribution (ie, the Gaussian curve) (Figure

1-12). With this distribution, most trauma victims

Fig. 1-12. Normal distribution of injury severity. In this

hypothetical population, the degree of injury severity at

which casualties would die if they receive poor medical

care falls higher on the curve than it does if the medical

care they receive is good.

Number of Casualties

Lethal Injury,

Good Medical

Care

Lethal Injury,

Poor Medical Care

Low Degree of Injury Severity Maximum

Fig. 1-13. If the distribution of injury severity is bimodal,

then the quality of medical care has less effect on mortality than it would if distribution were normal.

will have injuries of intermediate severity; there are

few minor or very severe injuries. A second possible curve has two peaks: this is known as a bimodal distribution (Figure 1-13). With this distribution, most trauma victims will have either minor or

severe injuries; a few will have injuries of intermediate severity.

The bimodal distribution, because of its peculiar

shape, seems intuitively unlikely; yet, some welldefined types of trauma have injury severity distributions of this shape. Figure 1-14 shows the distribution of injury severity found for domestic airplane

crashes in which at least one life was lost.49 The

indices of injury severity used here are very simple:

none, minimal, serious, fatal. A bimodal distribution is clearly apparent. Figure 1-15 shows the

injury severity distribution, quantitated in terms of

the Injury Severity Score, for a 1989 airplane crash

on the M1 motorway in England.50 Again, a bimodal distribution of injury severity is seen. Data

published in 199451 indicate that the distributions of

both the Trauma Score and the Glasgow coma scale

in typical populations of trauma victims are also

bimodal.

For didactic purposes, distributions shown in

both Figures 1-12 and 1-13 are assumed to have a

score above which all casualties will die even when

they receive medical care. However, the score associated with death will be higher with good care and

lower with poor. Figure 1-12 shows that improving

medical care will markedly increase the number of

survivors if the distribution is normal. By way of

contrast, Figure 1-13 shows that a similar improvement in the quality of medical care will be associated with much less salvage if the distribution is

Low Maximum

Lethal Injury,

Good Medical Care

Number of Casualties

Lethal Injury,

Poor Medical Care

Degree of Injury Severity
27

Combat Trauma Overview

35

30

25

20

15

10

5

0

Number of Casualties

Survived

Died

Number of Casualties

0

200

400

600

800

1,000

1,200

1,400

None Minimal Serious Fatal

Magnitude of Injury

Fig. 1-14. Distribution of the magnitude of injury in all

domestic airplane crashes during the period 1979 through

1984 in which one or more passengers were fatally injured. A bimodal distribution is apparent. Data source:

National Transportation Safety Board.

bimodal. In terms of military medicine, care of poor

quality might be thought of as military surgery as

practiced in the early part of the 20th century, and

good care might be military surgery as it is practiced at the end of the 20th century. Clearly, a major

reduction in mortality would be expected if injury

severity of combat casualties has a normal distribution, but a much smaller reduction would be expected if the real distribution has a bimodal shape.

Actual Distribution

Figure 1-16 shows the distribution of injury severity found for combat casualties in a sample taken

from the WDMET database.35 The distribution is

clearly not normal in shape but it is also less obviously bimodal than is the distribution shown in

Figure 1-15, primarily because of the peak in deaths

in the Injury Severity Score interval 20–29. Most of

the dead casualties who appear in this interval are

soldiers who had sustained penetrating head

wounds, the lethality of which is grossly underestimated by the Abbreviated Injury Scale. They are

assigned an Abbreviated Injury Scale score of 5, but

a more realistic assessment would be to assign them

a score of 6 (Injury Severity Score = 75). Most of the

dead casualties in the Injury Severity Score interval

20–29 should, therefore, be in the Injury Severity

Score interval > 60.

Given this needed change, there is no doubt that

the casualty population found in the WDMET study

is best described by a bimodal injury severity distri1–9 10–19 20–29 30–39 40–49 50–59 > 60

Injury Severity Scores

Fig. 1-15. Injury Severity Scores for the victims of the crash of a Boeing 737-400 onto the M1 Kegworth motorway in

England, 1989. The bimodal distribution of injury severity is apparent. Data source: Rowles JM, Kirsh G, Macey AC,

Colton CL. The use of injury scoring in the evaluation of the Kegworth M1 aircrash. J Trauma. 1992;32:441–447.
Anesthesia and Perioperative Care of the Combat Casualty

28

450

400

350

300

250

200

150

100

50

0

Number of Casualties

1–9 10–19 20–29 30–39 40–49 50–60 > 60

Injury Severity Scores

Died

Survived

morbidity of battle injuries—especially through the

decrease in wound sepsis.

Pathophysiological Causes of Death

Medical interventions designed to reduce combat mortality must be predicated on a thorough

understanding of the pathophysiological derangements that cause the death of injured soldiers. Figure 1-17, which is based on the WDMET study15 and

Arnold and Cutting’s paper38 on the causes of death

in medical treatment facilities in Vietnam, provides

the needed information. Mortality is classified as

killed in action due to exsanguination (44%), CNS

injury (31%), and combined injuries (13%); and died

of wounds due to CNS injury (5%), multiple organ

failure/sepsis (4%), and shock (3%).

Exsanguination was the most common cause of

death for U.S. ground forces in Vietnam, accounting

for about one half of the combat mortality in the

WDMET study. The most common sites of injury

were the heart, thoracic aorta, pulmonary artery,

and intraparenchymal pulmonary vessels. However, in about 20% of the casualties who exsanguinated on the battlefield, the site of bleeding was

Fig. 1-16. Distribution of Injury Severity Scores in a population of casualties from the Vietnam War. A bimodal

distribution is apparent, with most casualties falling into one of two populations: those with minor to moderately

severe injuries, and those with nonsurvivable injuries. Data source: Wound Data and Munitions Effectiveness Team

database.

bution. In simple terms, there are two major subpopulations: the larger one containing casualties

with minor or moderate injuries, and the smaller

containing those with critical and unsurvivable injuries. Only a small minority (perhaps 10%), those

with serious or severe injuries who fall between the

two major subpopulations at either end of the injury severity distribution, are likely to be helped by

trauma care of the highest quality and sophistication. Survival of the casualties at either end of the

injury severity distribution is not appreciably influenced by the quality of care. Those with minor or

moderate injuries do not die if given even a modicum of care, and those with critical or unsurvivable

injuries are beyond any conceivable help. What this

means for military medicine is that it will not be

easy to achieve a substantial decrease in combat

mortality because of the small size of the population

that is helped by surgical care of the highest quality.

These considerations are consistent with the relatively small decrease in combat mortality observed

in U.S. wars of this century.52 It must be emphasized

that this conclusion applies only to mortality and

not to the morbidity of combat injuries. Modern

military surgery has unquestionably reduced the
29

Combat Trauma Overview

Multi-KIA

13%

CNS-DOW

5% MOF-DOW

4%

Shock-DOW

3%

Exsang-KIA

44%

CNS-KIA

31%

Fig. 1-17. The pathophysiological causes of death in the

Vietnam War. Data from the Wound Data and Munitions

Effectiveness Team database show that exsanguination

and injury to the central nervous system were the most

common causes of death. Key: CNS: central nervous

system; DOW: died of wounds; Exsang: exsanguination;

KIA: killed in action; MOF: multiple organ failure; Multi:

multiple injuries. Data sources: (1) Wound Data and

Munitions Effectiveness Team. The WDMET Study. 1970.

(2) Arnold K, Cutting RT. Causes of death in United

States military personnel hospitalized in Vietnam. Milit

Med. 1978;143:161–164.

an artery in an extremity (femoral and brachial

were the most common), in which first aid could, in

theory, have been lifesaving.53 Death from shock at

the hospital level was uncommon, even though

some 10% of all WDMET hospital admissions were

judged by their surgeons as being in circulatory

shock.15(T4-7-9) Of the hospitalized casualties who

died of shock, roughly equal numbers were categorized as dying of continued bleeding (the sites were

most commonly the liver or pelvis), uncontrollable

coagulopathy, and “irreversible shock.” Given that

about 50% of the killed die by exsanguination, it

would appear from the WDMET data that about

18% of all casualties are at risk of dying from

exsanguination or shock, with the overall mortality

in this group being 60%.

The difficulty of affecting the outcome in the

remaining 80% of the casualties who die of

exsanguination is suggested by the data given in

Exhibit 1-2, which describe the clinical and anatomical features in 10 consecutive casualties in the

WDMET study who were killed in action but who

survived for 10 or more minutes after being fatally

wounded. It should be apparent that stabilization

by conventional first aid has little to offer to these

gravely wounded soldiers even though (a) they

lived long enough to receive battlefield first aid and

(b) had injuries that are much more surgically treatable than are wounds of the heart or aorta. Only an

intervention designed, in essence, to slow the process of dying until surgery can be carried out has

any possibility of preventing death in this group.

What is needed is a radically new approach to

battlefield stabilization, perhaps based on yet-tobe-discovered biochemical and biophysiological

interventions, which will make possible metabolic

down-regulation with consequent temporary suspension of cardiopulmonary function without causing permanent tissue injury. Finding successful

solutions to the combat casualty problems listed in

Exhibit 1-2 should be considered a challenge by all

military anesthesiologists.

Injury to the CNS was the second-most-common

cause of death in combat casualties studied by

WDMET. These injuries were almost always so devastating (eg, three or more lobes injured, avulsion of

the brain, decapitation, or injury to the brainstem)

that they offered little potential for better surgical

management to improve outcome. Surprisingly,

the most common cause of death at the hospital level

was CNS injury. The extent to which better care might

be able to decrease this cause of mortality is unclear:

one half of these casualties had been triaged into the

expectant category because they were considered

brain dead. The famous Bougainville study54 of

World War II reached the same conclusion regarding the relative importance of the pathophysiological causes of death: hemorrhage accounted for the

largest number of combat fatalities (55%), while those

who succumbed to injuries to the CNS composed the

second-largest group (26%).

Most of the WDMET casualties in the multiple

category had the misfortune to sustain potentially

lethal injuries to the head, chest, or abdomen. The

most common combinations were head and chest,

and chest and abdomen. Some of these casualties

sustained what was described as mutilating blast

injury, in which the body was essentially disintegrated, but others had combined injuries as a consequence of the propensity of assault rifles and machine guns to cause multiple wounds.
Anesthesia and Perioperative Care of the Combat Casualty

30

EXHIBIT 1-2

CLINICAL AND ANATOMICAL DIAGNOSES OF 10 CASUALTIES WHO DIED 10 OR

MORE MINUTES AFTER BEING WOUNDED

1. Casualty lived 15 minutes; perforating gunshot wound of chest; bullet entered at right anterior axillary

line and exited to the left of the spine above the iliac crest; pulmonary laceration, fracture of T12;

severed spinal cord; 2,000 mL of blood in right hemithorax.

2. Casualty lived about 10 minutes; through-and-through gunshot wound of abdomen; bullet entered

right flank and exited under left costal margin; celiac axis and superior mesenteric vein transected;

1,750 mL of blood in abdominal cavity.

3. Casualty lived less than 1 hour; perforating gunshot wound entered right shoulder and exited lower

abdomen; lacerations of right lung, diaphragm, liver, and kidney; a total of 1,600 mL of blood in chest

and abdomen.

4. Casualty died 10 to 15 minutes after being wounded: bullet entered laterally on the right side of the

abdomen and passed out of the left hip; autopsy showed transection of right internal iliac artery,

sigmoid colon, and left femoral artery, multiple perforation of small bowel; 1,750 mL of blood in

abdominal cavity.

5. Casualty lived 50 minutes; gunshot wound of chest with fractures of ribs 7, 8, and 9; small hemothorax

(250 mL); massive “traumatic atelectasis” of lung [pulmonary contusion?—RFB]; casualty became

unresponsive 2 minutes after being wounded and after he stated “I think I’ve got a punctured lung.”

6. Casualty lived 15 minutes; 2 gunshot wounds of the upper chest; one bullet, after fracturing T 4-5,

lacerated the trachea, esophagus, and one lung; second bullet passed through chest into abdomen,

where it injured the liver, kidney, and pancreas; 250 mL of blood in abdomen.

7. Casualty lived for 15 minutes; four gunshot wounds of left lateral hip and lower abdomen; extensive

fracture of pelvis; perforation of right common iliac artery; 1,000 mL of blood in abdomen.

8. Casualty may have lived for 15 to 20 minutes; two perforating gunshot wounds of left side of body; one

passed through the arm and entered the chest, where it fractured four ribs; no description of hemo- or

pneumothorax; second bullet fractured T10 and severed the spinal cord at that location.

9. Casualty lived for 20 to 25 minutes; bullet entered right flank and passed through liver, diaphragm,

and all lobes of right lung; several severely fractured ribs at wound of exit; 650 mL of blood in chest

and abdomen.

10. Casualty lived 10 to 15 minutes; perforating gunshot wound of abdomen with lacerations of liver,

duodenum, and kidney; 1,300 mL of blood in abdomen.

Data source: Wound Data and Munitions Effectiveness Team. The WDMET Study. 1970. Original data are in the possession

of the Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799. Three summary volumes

contain extensive abstracts of the statistical data and can be obtained from Defense Documentation Center, Cameron Station,

Alexandria, Virginia 22304-6145.

A minority of the casualties in the multiple category did not have true multiple injuries but had

respiratory tract wounds as the cause of death. It is

not unusual to find chest X-ray films of WDMET

dead that show the presence of a massive tension

pneumothorax. In casualties seen alive at the hospital level, about 3.2% were said to be in respiratory

distress: about one half had tension pneumothorax

and one half had an open chest wound. The importance of injury to the upper airway (face and neck)

as a cause of death on the battlefield is unclear; no

doubt it is much less important than exsanguination

or CNS injury. The WDMET study indicates that of

casualties who were alive when they reached a

medical treatment facility, about 1.3% required

immediate upper airway control.15(T4-7-9) However,

slightly more than one half of these casualties required airway control because of massive CNS injury; a minority only had direct injury to the upper

airway.

About 4% of the fatally wounded soldiers died

from what would now be called the systemic in-
31

Combat Trauma Overview

TABLE 1-5

PARTITION OF HOSPITAL DEATHS BY

PHASE OF MEDICAL MANAGEMENT

Phase of Management Deaths (%)

Dead on admission or died shortly 7.8

after admission

Died before anesthesia began 23.2

Died during anesthetic induction 1.1

Died during initial surgery 5.2

Died after initial surgery 62.7

Adapted from Snyder HE, Culbertson JW. Studies of Fifth US

Army hospitalized casualty deaths. In: Beyer JC, ed. Wound

Ballistics. Washington, DC: Department of the Army, Medical

Department, Office of The Surgeon General; 1962: 473.

flammatory response syndrome apparent as

multiple organ failure and sepsis. The most common manifestations were septic shock (usually

caused by severe peritonitis), adult respiratory distress syndrome, and acute renal failure. To put the

magnitude of these problems in perspective, about 1

casualty in 1,000 died of renal failure. Assuming that

the condition has a mortality of 50%, there would

have been about 2 cases of renal failure per 1,000

casualties.

THE ANESTHESIOLOGIST AND COMBAT CASUALTY CARE

Some civilian trauma anesthesiologists, most

prominently C. M. Grande,55 believe that trauma

anesthesiologists must go beyond their familiar role

in the operating room and become life-support

physicians in the broadest sense, involved in all

aspects of the casualty’s care. In combat casualty

care, however, the potential for lifesaving, nonsurgical intervention in the operating room is

somewhat limited. In lieu of data from a more

recent war, the data contained in Table 1-5 may be

taken as evidence for this contention.37 The table

stratifies by phase of treatment the deaths of 1,450

combat casualties, which occurred in hospitals in

the Fifth U.S. Army in Italy between January 1944

and May 1945.

Although these data are nearly 50 years old, they

suggest that it would be difficult to do much better,

because only 6.3% of the total hospital mortality occurred during the anesthetic induction and the operation itself. Where there is room for improvement is in

the preoperative, and especially in the postoperative,

phases. It is for this reason that the focus of this

book goes beyond anesthesia per se and puts strong

emphasis on perioperative care. Unfortunately, as

has been shown, the battlefield is the site of the great

majority (90%) of combat fatalities. For the concept of

the trauma anesthesiologist as life-support physician

to find its full realization, military anesthesiologists

must look beyond the hospital level to the battlefield. The military trauma anesthesiologist must be

prepared to assume a leadership role in providing

resuscitation at the first and second echelons of care.

Because the Advanced Trauma Life Support course

(ATLS)56 of the American College of Surgeons provides the scientific and doctrinal basis for AMEDD’s

initial care of combat casualties, it is necessary for

military trauma anesthesiologists to take a critical

look at ATLS as it is presently practiced.

Advanced Trauma Life Support Course

The ATLS course is a systematic approach to the

initial diagnosis and management of trauma victims. It emphasizes the recognition of immediately

life-threatening injuries and provides instruction in

the first-aid skills that are necessary to optimize

patient survival in the early postinjury period. In

the broadest sense, ATLS should be applicable to all

trauma victims. However, because it was developed by civilian physicians for managing civilian

trauma in a civilian setting, the military anesthesiologist should not be surprised to find that specific

aspects of ATLS are not entirely appropriate to

combat casualty care. There are significant differences in the epidemiologies of civilian and battlefield trauma. They arise not only from dissimilarities in the mechanisms of injury (eg, blunt trauma is

much more common in civilian life than in war), but

they also reflect the following characteristics of

military medicine:

• Military trauma management is echelon

(now also called level) based. Each echelon

either returns the soldier to duty or evacuates the casualty safely to the next echelon.

• Medical personnel are in much greater

physical danger when providing combat

casualty care than they are when providing

civilian trauma care (about 10% of the soldiers in the WDMET study were wounded

while attempting to help a casualty).
Anesthesia and Perioperative Care of the Combat Casualty

32

• Military trauma care is performed in an austere and resource-limited environment.

It is in the areas of organization and in what can

be called the conditions of practice that ATLS in its

usual civilian guise may need to be modified when

used to care for combat casualties in conventional

land warfare.

Military Organization for the Provision of Care

Both civilian and military trauma care depend on

an organized system of prehospital treatment. While

the civilian prehospital care organization typically

consists of ambulances and paramedics, the military prehospital system consists of two levels of

deployable medical facilities, ground or air ambulances, and attendant personnel numbering as many

as 600 for one division. The extensive nature of the

military prehospital system reflects the cost of providing a mobile and self-contained healthcare system for a large number of personnel who are subject

to a variety of infectious diseases and environmental hazards and, worse, exposed to a risk of violence

that exceeds anything in civilian experience by 1 or

2 orders of magnitude.

The military trauma care organization differs

from the civilian model by providing care by echelons, wherein military casualties are either returned

to duty or evacuated through successive echelons

that are capable of increasingly sophisticated care.

Table 1-6 describes the echelons of care and their

function. Resuscitative surgery—surgery performed to control bleeding and to eliminate contamination—is carried out at the third echelon (or at

lower echelons by a third-echelon forward surgical

team [FST]), while restorative surgery—surgery

performed to heal wounds and to restore function—is carried out at the fourth echelon or in the

continental United States (CONUS). In the civilian

system, the emergency department (the site of ATLS)

is in the same building as the operating room (the

site of resuscitative surgery). In the military system, ATLS is performed at the first and second

echelons (where it must be done if acute life-threatening processes are to be reversed), many kilometers (or hours, depending on the mode of evacuation) from the site of resuscitative surgery.

The contents of the preceding paragraph describe

the organization as prescribed by army doctrine,1

but exceptions do exist. During much of the Vietnam War, the first and second echelons of care were

frequently so atropic that third-echelon hospitals

had a function not too dissimilar from that of a

civilian trauma center. Casualties frequently arrived directly from the battlefield without having

received any care, which meant that first-aid interventions that ideally should have been performed

in the field were commonplace at the hospital level.

Still, the analogy with the civilian system was not

TABLE 1-6

LEVELS OF MILITARY MEDICAL CARE AND THEIR USUAL FUNCTION

Echelon/Level Medical Unit Trauma Management

First/Unit Medical platoon, BAS ATLS

Second/Division Medical company ATLS

Medical battalion Minor surgery

FST* Resuscitative surgery

Third/Corps MASH† ATLS

CSH Resuscitative surgery

Fourth/COMMZ Field hospital Reconstructive surgery

General hospital Reconstructive surgery

Fifth/CONUS Medical center Reconstructive surgery

*Surgical squads are organic to airborne and air-assault divisions and, in the form of forward surgical teams, may be attached when

needed to medical companies of other divisions.

†The MASH is to be deleted; its function will be assumed by the FSTs.

ATLS: Advanced Trauma Life Support; BAS: battalion aid station; COMMZ: communications zone; CONUS: continental United

States; CSH: combat support hospital; FST: forward surgical team; MASH: mobile army surgical hospital
33

Combat Trauma Overview

total because only resuscitative surgery, and not

reconstructive surgery, was normally carried out.

In recent years, the U.S. Army’s involvement in

peacekeeping operations, under the doctrinal guise

of operations other than war (OOTW),1(p1-1) has raised

the possibility that military anesthesiologists will

practice in a situation in which the functions of the

first three echelons of care are telescoped together

into one medical treatment facility. Military anesthesiologists may also have the opportunity to serve

in hospitals of the International Committee of the

Red Cross. Although typical military wounds are

treated in these circumstances, there are no echelons of care and the primitive economic infrastructure, the lack of medical resources, the underlying

social chaos, and a perhaps fatalistic acceptance of

death by the population being served create conditions that are likely to be new to most medical

officers in the U.S. military.57

Battlefield Conditions

Four factors—danger, austerity, casualty density, and goals—distinguish the military use of ATLS

from its use in the civilian sector.

Danger. Field medical units, especially those of

the first and second echelons, are subject to enemy

attack. Even necessary defensive measures, such as

entrenchment and construction of bunkers, may

prevent an optimal flow of casualties. Furthermore,

when the possibility of unconventional warfare

(chemical or biological) exists, even the individual

casualty must be considered a threat to the medical

troops, and appropriate steps must be taken to

reduce the risk of exposure. These dangerous possibilities may interfere with, or prevent the full

application of, ATLS as it is practiced in civilian

emergency care.

Austerity. Field medical units lack the pleasant

ambience of civilian hospitals. Tents, mud floors,

cots, and battery-operated lights are not insurmountable obstacles to the proper application of ATLS,

but they can reduce the efficiency of all but the most

ardent and most experienced practitioners. The

need to employ noise and light discipline complicates battlefield ATLS. The lack of many diagnostic

modalities, even such basic ones as X-ray units,

seriously impairs the ability of military physicians

to apply ATLS as practiced in the civilian sector,

especially in first- and second-echelon facilities.

Finally, medical supplies such as syringes, intravenous catheters, and even gloves are available in

limited amounts; they cannot be expended unless

there is good reason to believe that their use will

benefit the casualty. Furthermore, the wearing of

protective devices against communicable disease

(ie, the universal precautions) is not feasible in the

field echelons of care.

Casualty Density. Mass casualty situations are

not unique to the military, but mass casualty situations among civilians are usually considered atypical, while they are a constant threat in the military.

As has been described previously in this chapter,

the casualty-generating potential of the modern

battlefield is 10- to 100-fold greater than it is in even

the most violent urban setting. Although the ATLS

primary survey may take only a few seconds to

perform, the complete examination is not suited to

situations in which only a few minutes per casualty

are available for diagnosis and presurgical resuscitation.

Goals. ATLS is designed to assist the physician

in recognizing acute, life-threatening, pathophysiological disturbances. The focus is on lethality and

the prevention of gross morbidity. The military

anesthesiologist cannot forget that the missions of

the medical services—conserve fighting strength

and maintain the fighting power of the command—

can be carried out only if each casualty is assessed in

terms of his ability to return rapidly to duty. This is

not to say that the demands of military medicine

require that the seriously injured be ignored. Rather,

the slightly wounded should be accorded higher

priority for care than they would be if the military

medical treatment system were driven solely by

ATLS considerations of lethality.

Specific Aspects of Advanced Trauma Life

Support

The following is not to be construed as an attempt to replace ATLS with an alternative approach

to managing trauma. Instead, its purpose is to

indicate areas in which ATLS should be modified

when used in combat casualty care. Perhaps the

most important point is that ATLS must be tailored

to the echelon of care and to the prevailing tactical

posture. For example, in a quiet, third-echelon

surgical facility, the military practice of ATLS may

not deviate from the civilian standard, but this will

certainly not be true at a first-echelon facility that is

being shelled while it is receiving several dozen

casualties. In general, the more theoretically relevant ATLS may seem to be, the further forward on

the battlefield it must be implemented to be effective.

The realities of the battlefield are, however, that the

further forward the care is needed, the less practical it is

to provide.
Anesthesia and Perioperative Care of the Combat Casualty

34

Most medical officers, and certainly all military

anesthesiologists, will be ATLS trained, so only a

brief summary need be given here of the sequence

of events and their purposes:

• primary survey (with simultaneous correction of any life-threatening conditions):

° airway patency with cervical spine control,

° breathing and ventilation,

° circulation and hemorrhage control,

° disability, as determined by neurological

status, and

° exposure;

• triage determination, which may be made

as part of the primary survey;

• secondary survey (a detailed examination

of the casualty); and

• definitive care.

Fig. 1-18. Casualty care decision tree applicable to medical care at the field-echelon level. Three basic questions

need to be asked when a field medical provider is presented with a casualty. First, is the casualty a potential

threat (eg, chemically contaminated)? Second, does the

casualty require immediate lifesaving first aid? Third,

can the casualty be treated and returned to duty from this

echelon? Adapted from Bowen TE, Bellamy RF, eds.

Emergency War Surgery NATO Handbook. 2nd rev US ed.

Washington, DC: Department of Defense, Government

Printing Office; 1988: 204.

Casualty

Is the casualty

a threat?

Disarm

Decontaminate

Give first aid

Does the casualty

require lifesaving

first aid?

Can the casualty

be returned to

duty from this

echelon?

Evacuate

Treat

Return to Duty

No Yes

Yes No

No

Yes
35

Combat Trauma Overview

The following is a chapter-by-chapter critique of the

ATLS manual as it applies to combat casualty care.

Initial Assessment and Management

The triage algorithm from the Emergency War

Surgery NATO Handbook (Figure 1-18)58 is applicable to the first and second echelons of care, but it

may also be appropriate at facilities that provide

surgical care as well.

Medical officers must ask themselves three questions:

1. Is the casualty a threat? The threat comes

from casualties who have been contaminated by exposure to chemical or biological

agents. Intelligence sources (S-2, G-2) will

usually know if the enemy has the capability and the intent to employ unconventional weapons.

2. Does the casualty require emergency lifesaving resuscitation? Medical officers

should require no more than a few seconds

to determine whether interventions utilizing the ATLS lifesaving skills are needed.

As has been indicated previously, the Vietnam War experience showed that about

15% of combat casualties benefited from

ATLS airway (1.3%), breathing (3.2%), and

shock (10%) interventions.

3. Can the casualty be returned to duty from

this echelon? A problem-oriented approach

is required: Where is the wound and what

is its nature? The medical officer must not

waste time preparing a comprehensive list

of all the possible diagnoses and certainly

should not spend time and effort ruling out

a large collection of diagnoses that are likely

to be important only in the context of ATLS

as it is practiced in a civilian emergency

department. If the wound will prevent the

casualty from performing his duty, and if

the treatment capabilities of the echelon

cannot reverse the pathophysiology of the

injury, then the casualty must safely and

expeditiously be evacuated to the next echelon.

Many aspects of the complete ATLS program are

not applicable to combat casualty care. For example, it is a mistake to cut off all the casualty’s

clothing to perform the complete ATLS examination. Not only can climatic conditions make this

unwise, but a fresh uniform will not be available as

a replacement. Performance of the secondary survey should be left to medical officers at higher

echelons. This is especially true because the necessary diagnostic modalities are absent in the battalion aid station, medical company, and even some

third-echelon hospitals.

Airway and Ventilatory Management

Combat casualties (exclusive of those with a severe brain injury) who require airway management

almost always have such destructive wounds that a

surgical airway (tracheostomy or cricothyroidotomy) will be required. The possibility that a

casualty whose upper airway problem is the result

of a penetrating wound will also have a subtle,

unrecognized, coexisting injury to the cervical spine

is so remote that it may be ignored. Airway control

in combat casualties with facial or neck wounds is a

necessary but not a sufficient therapeutic intervention; safe evacuation to the third echelon of care will

be impossible unless hemorrhage into the oral cavity can be stopped, or at least free egress of blood

from the mouth can be achieved.

Shock

Hemorrhage is the major cause of death in combat casualties. In about 20% of those casualties at

risk of exsanguination,53 bleeding can be controlled

by first-aid techniques such as applying pressure at

the site of hemorrhage or applying a tourniquet.

The latter intervention is especially useful when the

site of bleeding is from an amputation stump. There

can be little doubt that of the ATLS lifesaving interventions, those associated with the control of

bleeding are most important. Nevertheless, the

associated intervention—starting two large-bore intravenous lines and infusing 2 L of Ringer’s lactate—although having the status of established

dogma, has recently been called into question by

numerous laboratory studies on experimental animals and human clinical trials.59,60 It seems well

established that infusion of a crystalloid fluid will

elevate the systemic blood pressure and thereby

potentially increase the rate of hemorrhage from

injured vessels. The rationale for administering

intravenous fluids in a casualty with ongoing, uncontrolled hemorrhage can only be that a net increase in intravascular volume will take place, and

this will occur only if the fluid is infused faster than

it can leave the vascular bed. There is an obvious
Anesthesia and Perioperative Care of the Combat Casualty

36

limit to this approach: as was demonstrated during

the Vietnam War, massive administration of crystalloid fluid without concomitant rapid control of

bleeding may very well result in a degree of

hemodilution incompatible with life (ie, the “white

blood syndrome”).

The value of ATLS in the management of combat

casualties in shock will depend on the echelon of

care. Clearly, when surgical care is immediately

available, the ATLS shock module should be entirely appropriate. Its value at the first and second

echelons, where resuscitative surgery is usually not

available, is less obvious. It would indeed be ironic

if it were to be shown that the importance placed on

asanguineous fluid resuscitation in the field of casualties in shock from uncontrolled bleeding did

more harm than good. It becomes even more ironic

when we are reminded of the World War II experience

with fluid resuscitation and combat casualty care:

When internal hemorrhage persisted...there could

be no resuscitation without surgery, and it was

wasteful of both time and blood to attempt to raise

the patient’s blood pressure to normal before operation. The blood or plasma which was administered merely leaked into the traumatized regions

and was wasted....36(p6)

It is uncertain at this time what should be done

about fluid resuscitation in casualties with ongoing

hemorrhage, in circumstances in which surgical

control of bleeding is not immediately possible. An

experimental study published in 199361 showed that

although infusion of crystalloid fluid during uncontrolled hemorrhage did increase the magnitude

of the blood loss, infused animals lived longer than

controls that received no fluid. The magnitude of

the volume infused is important because both the

1993 study and another one published in 199262

found that survival was better when the volume

infused did not exceed 40 mL/kg. Some intravenous fluid may be better than none at all, as was

appreciated in World War II:

[Plasma] superbly fulfilled the role of supporting

life until transportation could be accomplished to

an installation at which whole-blood transfusion

was feasible.... By temporarily sustaining a seriously falling blood pressure and increasing the

cardiac output, it kept the patient alive long enough

for more effective measures to be taken.36(p22)

Nevertheless, there are limits to how long such

stabilization will be effective. Until asanguineous

oxygen-carrying blood substitutes are developed,

there is no substitute for immediate surgery in the

rapidly exsanguinating casualty; nonsurgical stabilization is an act of futility.

There is an additional area in which the realities

of battlefield medicine intrude on the performance

of ATLS. Invasive monitoring techniques will not

be available in the first three echelons of care; thus,

clinical signs will need to be followed during volume replacement. In this regard, the World War II

and Vietnam War experiences showed that

tachycardia was an unreliable and inappropriate

indicator of the degree of shock.63

Thoracic Trauma

Casualties with thoracic wounds who survive to

be evacuated from the battlefield should be treated

following the ATLS algorithm; however, a penetrating chest wound is itself an indication for inserting a chest tube. Reinfusion of shed blood may

be possible because autotransfusion devices are

being added to the table of organization and equipment (TOE) of third-echelon facilities. Thus, ATLS

principles are appropriate, but sepsis remains the

main potential source of morbidity. Cardiac

tamponade is seen very uncommonly. The decision

to perform a pericardiocentesis is usually predicated on the presence of shock that is unresponsive

to fluid administration in a casualty who has a

wound of the anterior chest wall.

Abdominal Trauma

Casualties with abdominal wounds should be

treated by the ATLS algorithm, but the following

facts need emphasis:

• Among casualties who have abdominal

wounds and who survive to be evacuated

from the battlefield, the major threat to life

is sepsis from peritoneal contamination

rather than shock from hemorrhage. Thus,

antibiotic coverage needs to be emphasized.

• Indications for operation are simpler than

suggested by ATLS; the presence of a penetrating wound is sufficient justification.

Peritoneal lavage as mandated by ATLS has

no role in the management of combat casualties with penetrating wounds.

Head Trauma

Casualties with penetrating head wounds who

survive to reach a medical treatment facility fall
37

Combat Trauma Overview

into two main categories: (1) those with tangential

gunshot wounds of the skull, with laceration of the

brain caused by bony fragments that are driven into

the brain parenchyma; and (2) those with penetrating wounds of the brain made by one or two small

fragments. Most surviving casualties will be conscious at the time of admission and will have high

Glasgow coma scale scores. Thus, the ATLS minineurological examination is needed to establish

evacuation and treatment priorities. If these casualties fail to receive neurosurgical care within 24

hours, they are at risk of developing potentially

fatal cerebral sepsis. A combat casualty who is

comatose secondary to penetrating head wounds

has a very poor prognosis. In the absence of

neurosurgical intervention, the best that can be

done is to assure an open airway by inserting an

endotracheal tube.

Spine and Spinal Cord Trauma

ATLS and the reality of combat casualty care

have their greatest potential conflict with spine and

spinal cord trauma. Penetrating missiles that wound

the cervical, thoracic, or lumbar spine have a high

lethality because the missile has a propensity to also

strike contiguous structures (eg, the carotid artery

or thoracic aorta). Wounds of the cervical spine

may or may not involve the cervical cord, but when

they do, the outcome is almost always fatal (98%).15

There is no evidence that a penetrating missile

wound that involves only the cervical spine will

predispose the patient to a subsequent cervical spinal cord injury when the neck is manipulated. Essentially no combat casualties with penetrating neck

wounds will benefit from immobilization of the

cervical spine, except the rare living casualty who

has an existing neurological defect that is thought

to be caused by a spinal injury.64 Given the wellestablished danger of carrying out care on the battlefield, battlefield immobilization of the neck of a

casualty with a penetrating neck wound is therefore

unwarranted. However, ATLS principles do apply

to casualties with blunt trauma to the head and

neck.

Extremity Trauma

During the pre-ATLS era, much of field medical

training consisted of practicing the application of

dressings and splints to casualties with fractures or

soft-tissue wounds of the extremities. In fact, these

remain the essential skills required to give effective

combat casualty care at the first and second echelons. For the military ATLS trainer, the chapter in

the ATLS manual on extremity trauma is the important chapter. Emphasis should also be placed on the

prehospital administration of antibiotics that will

decrease the potential for clostridial and streptococcal wound infections.

Third-echelon extremity care will differ from

ATLS practice because the radiographic equipment

necessary to rule out vascular injury will probably

not be available. Although Doppler probes may be

available to assist in making the diagnosis of a

vascular injury, the diagnosis will usually have to

be made by exposing the vessel at the time of softtissue wound management.

Burns

Inhalation injury is a major source of mortality

and morbidity during naval warfare and will probably become more important in future land warfare

because of the prevalence of armored fighting vehicles. Medical officers at field medical facilities

should predicate their therapies on the burned

casualty’s ability to clear the tracheobronchial tree.

If secretions cannot be raised, the medical officer

will have to decide whether scarce resources should

be used for intubation and ventilation. Bronchospasm must be broken and pneumonitis must be

prevented or treated. Antibiotic treatment may

have to be initiated without the physician’s knowing the specific bacterial flora that is growing in the

lung, undesirable as this may be. In an important

departure from ATLS, topical antimicrobial therapy

such as with Sulfamylon (manufactured by Don B.

Hickon, Inc., Sugar Land, Tex.) or Silvadene (manufactured by Marion Merrell Dow, Inc., Kansas City,

Mo.) burn cream should be started before the casualty is evacuated from the field echelons. The appropriate escharotomies should be performed early

when treating a casualty with deep, third-degree

extremity burns whose evacuation to a higher echelon is likely to be delayed.

Stabilization and Evacuation

Stabilization and evacuation of casualties are

aspects of ATLS that are difficult to implement

fully. There is no 911 number to call on the battlefield nor will the referring physician be able to

contact the receiving physician. In these respects,

the military and civilian trauma-care systems are

markedly dissimilar. At the unit and division

levels, medical officers will need to know how to

contact the supporting ambulance unit for either
Anesthesia and Perioperative Care of the Combat Casualty

38

air or ground evacuation. At the third echelon, the

evacuation, which will usually be done by the U.S.

Air Force, will be organized by the medical regulating officer.

Regardless of the echelon, the medical officer

will be responsible for establishing priorities for

evacuation and treatment. ATLS concepts can usefully be combined with existing military criteria for

triage at first- and second-echelon medical facilities:

• Priority I—URGENT and Priority IA—URGENT-SURG: the casualty fails to respond

or responds transiently to ATLS airway,

breathing, and circulation (ABC) skills;

• Priority II—PRIORITY: the casualty responds to ATLS ABC skills and remains

stable; and

• Priority III—ROUTINE: ATLS ABC skills

are not needed to stabilize the casualty.

Note: casualties with massive injuries to large muscle

masses (such as the thigh or the pelvis) and casualties with open comminuted fractures of the femur

or the hip should be triaged into the priority category because of the propensity of such wounds to

develop anaerobic sepsis.

ATLS concepts can also be used to establish treatment priorities not only at first- and second-echelon

facilities but also for third-echelon war surgery:

• Urgent: this triage category includes the

uncommon casualty who is at risk of rapid

death after an injury that causes airway

compromise, respiratory derangement, or

shock that is not responsive to ATLS stabilization. Emergency surgery must be performed within minutes for there to be any

hope that the casualty will survive.

• Immediate: this triage category includes

most casualties with abdominal or chest

wounds who responded to ATLS emergency

lifesaving skills and those with extensive

soft-tissue and bony injuries, especially

when a major vascular injury is present.

Surgery is needed within 6 hours.

• Delayed: this triage category includes most

casualties with fractures or soft-tissue

wounds. ATLS ABC skills are not needed,

but surgical care must be provided within

12 to 24 hours.

• Minimal or ambulatory: this triage category

includes casualties who are carded for

record only. These soldiers require outpatient treatment and should not be evacuated to higher echelons.

• Expectant: this triage category includes casualties whose injuries are so severe that

they cannot reasonably be expected to survive given the available medical care. Those

who are brain dead or who have deep burns

over much of their bodies are in this category. These casualties are not evacuated

from the echelon that assigns this priority.

The assignment of treatment or evacuation priorities is a dynamic process. The medical officer

must continually update priorities. For example, a

casualty who is in the delayed category may become immediate. Similarly, a casualty’s category

will be influenced by the prevailing tactical situation and the availability of medical resources. Given

an unfavorable tactical situation, a casualty who

might otherwise be classified in the urgent or the

immediate category may have to be classified in the

expectant. The converse is occasionally true: a

casualty who has been classified as expectant may

be retriaged into the urgent category because more

medical resources have suddenly become available.

Furthermore, priorities need to be reassessed for

treatment and subsequent evacuation on arrival at

the receiving echelon. Triage is ongoing, and no

decision should be considered final.

SUMMARY

Although catastrophic attrition from disease or a

hostile environment is an ever-present threat in

military operations, battle injury is likely to assume

an increasing proportion of attrition compared with

the historical norm. The magnitude of the attrition

depends on the size of the units engaged, their

tactical posture, and the intensity of the warfare.

Typical battle casualty rates in war are 10- to 100-

fold greater than the rate found for civilian trauma.

In contrast to civilian trauma, where blunt trauma

predominates, combat injuries are overwhelmingly

(> 90%) penetrating in origin. Explosive munitions

are the most common sources of penetrating missiles in modern warfare. The location of penetrating injuries is, to a first approximation, a function of

the size of the body surface over the body regions,

except that the head sustains about twice as many

injuries as would be expected on the basis of its
39

Combat Trauma Overview

surface area alone. Surviving casualties usually

have injuries to bones or skeletal muscle, while

those who are killed most commonly have wounds

to the head or trunk.

The mortality of combat trauma is commonly

measured by two normalized statistics: the percentage who are killed in action, and the percentage

who died of wounds. The former category includes

soldiers who expire on the battlefield, while the

latter category includes those who expire while

receiving treatment at a medical facility. Typical

historical data from recent wars indicate that about

20% to 25% of casualties are killed in action and

about 3% to 5% die of wounds. Penetrating missile

wounds of certain organs have a very high probability of death: wounds of the brain (about 4 of 5);

wounds of the chest (about 3 of 4).

Morbidity in combat casualties results in

noneffectiveness following a combat injury, which

can be measured as man-days lost. The distribution

of injury severity in combat casualties has a bimodal appearance with two major subpopulations: the

larger consists of soldiers with minor or not–lifethreatening (albeit frequently incapacitating) injuries; the smaller subpopulation consists of soldiers

with critical and nonsurvivable injuries.

The ATLS course of the American College of

Surgeons is the basis for initial assessment and

resuscitation of combat casualties. However, modifications in ATLS are necessary to make it compatible with the realities of combat casualty care in

three areas: the nature of the injuries, the organization of the military medical system, and the conditions of practice on the battlefield.

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53. Bellamy RF. The causes of death in conventional land warfare: Implications for combat casualty care research.

Milit Med. 1984;149:55–62.
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54. Oughterson AW, Hull HC, Sutherland FA, Greiner DJ. Study on wound ballistics—Bougainville campaign. In:

Beyer JC, ed. Wound Ballistics. Washington, DC: Department of the Army, Office of The Surgeon General; 1962: 373.

55. Grande CM. The trauma anesthesia/critical care specialist. In: Grande CM, ed. Textbook of Trauma Anesthesia and

Critical Care. St. Louis, Mo: Mosby–Year Book; 1993: Chap 5: 93–105.

56. Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians:

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60. Martin RR, WH Bickell, PE Pepe, JM Burch, KL Mattox. Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: A preliminary report. J Trauma. 1992;33:354–362.

61. Sindlinger JF, Soucy DM, Greene SP, Barber AE, Illner H, Shires GT. The effect of isotonic saline volume

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environment. J Trauma. 1989;29:332–337.
Combat Anesthesia Overview

43

Chapter 2

COMBAT ANESTHESIA OVERVIEW

DENVER E. PERKINS, M.D.*

THE BATTLEFIELD MEDICAL ENVIRONMENT

Technological and Logistical Support

Complexity of the Medical Network

Nature of the Evacuation Scheme

Pace of Operations

Interventions Prior to Surgery

THE EXPANDED ROLE OF ANESTHESIA PROVIDERS IN BATTLEFIELD

HOSPITALS

Education and Training Before Deployment

Training the Team After Deployment

Special Problems With Blood and Blood Products

Essentials of Readiness: Equipment, Training, and Attitude

*Colonel, Medical Corps, U.S. Army; Deputy Commander for Clinical Services, 44th Medical Brigade, Fort Bragg, North Carolina; Assistant

Chief, Anesthesia Service, Walter Reed Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

44

THE BATTLEFIELD MEDICAL ENVIRONMENT

As key players in a small unit, the anesthesia

providers in deployed hospitals have the ability to

influence the most vital aspects of the unit’s performance, both directly through their actions and

indirectly through the examples they set. Delivering anesthetics for combat casualties is always

challenging, frequently difficult, and occasionally

dangerous. The patient population overseas will

differ from the typical emergency room caseload

in hospitals in the continental United States (CONUS). Combat casualties will include a great number of patients with high-velocity wounds and

multiple surgical problems. In addition, military

hospitals invariably become active in caring for

casualties among the indigenous civilian population, who may present with any number of medical

challenges. The operating room environment may

be quite different from that found in the usual

stateside fixed facility. The prospect of working

in ISO (International Standards Organization)

shelters and TEMPER (tents, extendable, modular, personnel) tents with unfamiliar field anesthesia machines (eg, the Ohmeda 885A, manufactured by Ohmeda, Inc., Madison, Wis.) represents a

dramatic departure from the norm. The growing

emphasis on far-forward surgery introduces the

likelihood that anesthetic procedures will be performed in tents or shelters of opportunity with

draw-over devices. The pace of operations on the

battlefield may also differ significantly from the

routine in a civilian hospital. As opposed to carefully managed surgical caseloads planned weeks in

advance, there will be unpredictable pulses of emergent patients that will temporarily overwhelm the

surgical and evacuation systems. These periods

may be followed by weeks or months of waiting—

a condition of monotonous inactivity that many

medical personnel find almost intolerable. To further complicate matters, all this usually takes place

in a remote location at the end of a long and complex

chain of logistical and technical support. In any

deployment, there will be major problems to be

mastered arising from not only the nature of

the medical environment but also the support structure and the pace at which casualties are received

and evacuated. However, the physicians and nurses

of the U.S. Army Medical Department have a

long and proud history of adapting to unusual

circumstances and meeting difficult challenges.

Wounded U.S. soldiers have always received

excellent medical care in the past. The continuation

of that fine tradition depends in large part on the

determination and skill of the people reading this

book.

Technological and Logistical Support

The degree of sophistication and permanence of

the medical environment may vary greatly from

place to place, even at the same time and in the same

war. During Operation Desert Storm (the Persian

Gulf War, 1991), some hospitals attached to major

armored units lived and operated under the most

austere field conditions, moving frequently in desperate attempts to keep up with the extremely mobile tactile forces. Other medical units in this

same conflict worked without interruption in hospitals in Riyadh, Saudi Arabia, with modern, firstrate equipment at their disposal. The former group

had to learn field medicine in its most extreme form;

the latter, only to decipher the labels on their machines (which were in French and Arabic). The

anesthesia providers working from tents did very

few spinal anesthetic procedures for a number of

reasons, among them relatively low lighting levels,

unstable tables, and ambient dust. The groups in

the fixed facilities, however, were free to use whatever techniques they deemed appropriate for their

patients.

Complexity of the Medical Network

An equally important consideration is the extent

of the theater medical network. In the Persian Gulf

War, the U.S. Army had 44 field hospitals and a

highly developed evacuation system in place. It

was possible, within limits, to transfer patients from

one facility to another. This allowed for a certain

amount of flexibility. In direct contrast, in Operations Continue Hope and Restore Hope in Somalia

(1993–1994), the U.S. Army’s task force had one 24-

bed combat support hospital that served as the only

facility for 3,000 U.S. soldiers and as the principal

third-echelon facility for 20,000 other United Nations–coalition peacemaking troops. In this latter

instance, there were four functional operating room

tables in the theater. The fact that regional anesthetic techniques such as bupivacaine brachial

plexus blocks were extremely rare had nothing to

do with the nature of the soldiers’ wounds. It was
Combat Anesthesia Overview

45

a decision based on time, space, and the need to be

constantly ready for the next influx of emergent

cases.

Nature of the Evacuation Scheme

Operation Just Cause (Panama, December 1989)

involved the initial use of forward surgical teams

operating as the receiving and stabilization point

for an evacuation plan that employed one (albeit

one very long) move. After casualties received their

surgical treatment in the field hospitals, they were

transported by fixed-wing aircraft to CONUS hospitals in San Antonio, Texas, which functioned as

the equivalent of third- and fourth-echelon deployed

hospitals. The air-transport leg of the move took

about 8 hours.

Casualties from the Persian Gulf War faced a 6- to

8-hour, fixed-wing flight from the deployed theater

hospitals to fourth-echelon facilities in Germany.

Because of the size and complexity of that conflict,

there was some variation in the time to transport

from the site of injury to the stabilizing hospitals.

Additionally, there was some variation in the capabilities of the facilities in the chain proximal to

Landstuhl, Germany.

Operations Continue Hope and Restore Hope

in Somalia presented another variation on this

theme. As in Panama, there was a single receiving

and stabilization point, and the flight time to the

facility in Landstuhl was quite long: 11 hours. However, casualties of the African conflict were stabilized

in a mature field environment prior to transport.

The U.S. Army’s field medical treatment facilities in

Somalia, although based in TEMPER tents, had a

computed tomography scanner, sophisticated intensive care units, and other advanced technological support.

The plan for medical support of the operation

in Haiti (Operation Restore Democracy, 1994)

was quite different. In addition to four surgeons

and five anesthesia providers being scheduled to

jump in with the 82nd Airborne Division, the

USN Comfort (an enormous and quite sophisticated

hospital ship) was standing just offshore to receive

casualties. Had the planned U.S. incursion met

significant resistance, a great number of casualties

with traumatic injuries would in all likelihood

have been stabilized in the field and then evacuated

by rotor-wing aircraft directly to the operating

rooms of the Comfort. That environment would

have been an almost exact parallel of a civilian

level 1 trauma center in a major urban center in the

United States.

Pace of Operations

A mass casualty situation exists when the number of emergent patients exceeds a facility’s

resources. If there is one operating room table

and one surgeon, then it only takes two casualties

both triaged in the surgically “immediate” category

to throw that facility into a mass casualty situation. On the other hand, if there are 20 operating room tables and 20 surgeons, then 19 simultaneous emergent casualties represent business as

usual.

Two examples from recent conflicts illustrate

this point. One week after the fighting had stopped

in the Persian Gulf War, some U.S. Army field

hospitals experienced a massive influx of Iraqi soldiers who had sustained serious but nonlethal

wounds up to 2 weeks before surrendering. These

circumstances created an instant backlog of

nonemergent cases. In this unusual situation, the

anesthesiologists had the luxury of doing regional

techniques if they thought the operating room environment was suitable. There was no compelling

need for their hospitals to operate at absolute maximum efficiency in order to be prepared for the next

mass casualty situation.

Two years later, anesthesiologists in field hospitals in Somalia found themselves in exactly the

opposite situation. During the 5 June and 2 October

mass casualty situations in 1993, more than 50 emergency surgeries were performed in about that many

hours. Every casualty was assumed to have a full

stomach and underwent a rapid-sequence, general,

endotracheal anesthetic, regardless of the site of

injury. The determining factors in these two situations pertained to

• the limited surgical resources in theater,

• the impracticality of deploying timely medical reinforcements from Germany or CONUS, and

• the uncertainty of the tactical situation.

The foremost consideration was the most efficient way to use operating room time—to get as

many cases done in as short a time as possible to

free the operating rooms for the following wave of

casualties.
Anesthesia and Perioperative Care of the Combat Casualty

46

Interventions Prior to Surgery

The general ideas involved in treating the trauma

patient are quite simple. There are, essentially, four

things to be done: (1) establish an airway, (2) establish high-capacity venous access, (3) replace volume appropriately, and (4) get the patient to the

operating room as soon as possible for definitive

treatment. Actually achieving these goals, however, may be difficult or even, at times, impossible.

The first order of business is, as usual, the airway. Many anesthesia providers involved in trauma

care have independently arrived at a simple and

effective way of determining airway competence: if

a patient can talk, the airway is competent. The

indications for intubation include coma or shock, as

well as the need to protect the airway, relieve obstruction, deliver positive pressure breathing, or

perform tracheal toilet. A semiconscious, combative, or otherwise uncontrollable patient may have

to be paralyzed and intubated for further diagnosis

and treatment to proceed. As a general rule, anesthesia providers should be fairly aggressive in their

approach to questionable airways, especially among

the many distractions of mass casualty episodes.

Most casualties intubated prior to entering the

operating room will be facing one or more lifethreatening medical problems. Many will be comatose. The wisest pharmacological approach to these

patients is to do as little as possible in terms of

depressing their cardiovascular systems while securing an airway. This means doing a lot of

intubations with no drugs at all (or with only a

muscle relaxant) and accepting a relatively high

degree of postevent awareness.

One straightforward approach to the combat casualty with traumatic injuries is diagrammed in

Figure 2-1; the following guidance pertains across

the spectrum of combat casualty care:

• If the casualties arrive at a measured, controlled pace, if the available medical personnel match the number and kind of casualties, and if the equipment is optimal, then

use the same techniques you would apply

in your routine practice.

• If the casualties arrive at a controlled pace

and do not outnumber the available medical personnel but if the equipment is less

than optimal, then do the best you can with

what you have.

• If the casualties outnumber the medical

personnel required, then a mass casualty

situation exists and the casualties must be

triaged into the appropriate categories.

All casualties are considered to have full stomachs.

Nasotracheal intubation is rarely indicated when

dealing with acute trauma. A blind approach in an

unconscious casualty is generally unwise due to the

high likelihood of vomiting and aspiration. Also, it

is possible for a tube passed through the nose to

enter the cranial cavity. Casualties who have significant facial trauma or who are unconscious should

be treated as if they have unstable cervical spines.

Most casualties with acute trauma, then, will be

orally intubated using a rapid-sequence technique

involving Sellick’s maneuver while an assistant

holds in-line manual traction.

Safe Anesthetic Induction

Generally, severely injured casualties are

intubated before they come to surgery. All patients

with severe or multiple injuries should be placed on

100% oxygen. The reasonable assumption is that

the casualty’s condition is going to improve at some

time during the surgery. As the patient’s sensorium

improves, so may his tendency to move. Therefore,

the first drug administered is usually a muscle

relaxant. Narcotics or inhaled agents are cautiously

added as vital signs, urinary output, and other

parameters of cardiovascular stabilization are manifested.

If the casualty reaches the operating room

unintubated and conscious, then great care must be

taken not to destabilize the situation with induction

drugs. Which drug is used (ketamine and etomidate

are two reasonable choices) is not as important as

the care taken in its administration. Once again, a

certain amount of awareness on the part of the

casualty is unavoidable when dealing with trauma—

not desirable, just inevitable.

Gaining Venous Access

Venous access is easy to talk about but can

be incredibly difficult to achieve, especially in a

hypothermic or hypovolemic casualty. Two 16-

gauge intravenous lines should be considered the

minimum, and some units routinely start three

or four. The point is to get some sort of serviceable access quickly. Techniques to enter central

veins and surgical cutdowns should be considered

very early if initial attempts at peripheral sites are

fruitless.
Combat Anesthesia Overview

47

Gain intravenous access

(two 16-gauge needles) Establish airway, oxygenate, ventilate

Transport to location appropriate

to triage classification

Breathing?

Assume full stomach*

Suspect unstable neck†

Apneic or with massive facial trauma?

Successful? Unsuccessful? Successful? Unsuccessful?

Obtain surgical airway

Gain venous access and transport to

destination according to triage classification

Yes No

Fig. 2-1. Algorithm for initial treatment of casualties with traumatic injuries.

THE EXPANDED ROLE OF ANESTHESIA PROVIDERS IN BATTLEFIELD HOSPITALS

Education and Training Before Deployment

The familiar maxim holds true: during emergencies and times of crisis, a few people will rise to the

occasion and perform unexpected heroics, but most

of us will default to the level of our training. Ideally, education in emergency and trauma medicine

begins in nursing or medical school and progresses

through specialty training. At least some exposure

to trauma surgery prior to deployment is highly

desirable, not only to reinforce the important anesthetic issues surrounding these cases but also to

acclimate anesthesia providers to the pace and stress

of this environment. A rotation through a level 1

*All casualties with traumatic injuries should be treated as if they had full stomachs.

†In the absence of compelling historical or radiographic evidence to the contrary, unconscious casualties should be treated as if they

have unstable cervical spines.

Patent Airway?

Orotracheal intubation with in-line

manual cervical traction

Nasotracheal or orotracheal intubation

with in-line manual cervical traction
Anesthesia and Perioperative Care of the Combat Casualty

48

trauma center during the second or third year of

training is highly desirable. Not all U.S. Army

anesthesia residency programs and certified registered nurse anesthetist (CRNA) training programs

have formal trauma rotations. This issue is currently being addressed and will be changed in the

near future.

Because deployed hospitals generally function

as more-or less-isolated units and cannot expand

their personnel rosters in response to emergencies,

certain medical specialists may be forced to expand

their professional borders. Anesthesiologists are

particularly flexible members of the trauma team.

These physicians, with special training in airway

management and resuscitation, are capable of moving between the triage/emergency medical treatment/preoperative tent (usually called the emergency tent), the operating room, and the presurgery

holding areas to support the most intense resuscitative efforts.

One of the most serious problems in managing

protracted mass casualty exercises is the timely

detection of significant deterioration in the patients

awaiting surgery. When all the surgeons are in the

operating rooms, the job of reassessing the casualties in the delayed and immediate triage categories

who are awaiting surgery may fall to the anesthesiologist, who has some knowledge of trauma and

may be able to leave the operating room, whereas

the scrubbed-in surgeon cannot. A casualty with a

gunshot wound to the abdomen who has stable

vital signs may be triaged in the delayed category.

However, if this casualty begins to bleed and becomes unstable, his category can change to immediate with little or no warning. A system that guarantees relentless, frequent reevaluation of all casualties

awaiting surgery is essential to a well-run trauma

facility. Clearly, a surgeon is the medical professional most qualified by training to perform this

function; an anesthesiologist is perhaps the next

best in a crisis.

If new casualties arrive at the facility after all the

surgeons are already committed to the operating

rooms, it frequently falls to the anesthesiologist

(military occupation specialty [MOS] 60N) to participate in the initial triage and to act as an intermediary between the medical officers in the emergency tent and the surgeons in the operating room.

Once again this job usually falls to the anesthesiologist because he is a known entity to the surgeon, has

some knowledge of trauma and resuscitation, and

has some freedom of movement. For this reason, all

deployed physicians, not just emergency-treatment

specialists and surgeons, should have the training

necessary to perform triage and to perform the

initial assessment on casualties with multiple trauma

and high-velocity missile wounds.

Certified registered nurse anesthetists (MOS 66F)

not committed to the operating room may be stationed in the EMT (emergency medical treatment)

area to provide immediate airway support for newly

arriving casualties, or they may provide the same

care to casualties in the intensive care unit whose

condition is deteriorating. Certified registered nurse

anesthetists have considerable expertise in achieving vascular access and placing intraarterial and

intravenous monitoring lines. Physicians and nurses

in the EMT, recovery room, and intensive care unit

should be made aware of this expertise and be

encouraged to ask for assistance from the anesthesia teams.

Because of the diversity of tasks that anesthesia providers may be expected to accomplish, anesthesiologists and nurse anesthetists should be particularly aggressive in seeking relevant experience

in the emergency department and intensive care

unit—both while they are in training and during

their continuing medical education. Even if an

anesthesia provider has had formal training in

trauma, it is beneficial to direct a reasonable amount

of continuing medical education effort in this direction. As a minimum, all providers should have the

American College of Surgeons’ current Advanced

Trauma Life Support (ATLS) training. ATLS is

directed toward care of civilians suffering blunt

trauma, and it does not cover all aspects of war

trauma. However, the ATLS system provides a

solid background in casualty assessment, and the

effectiveness of that program has been borne out in

every conflict since Operation Urgent Fury

(Grenada, 1983). If at all possible, reading and

conferences should include enough material on highvelocity missile injuries to acquaint the provider

with a basic idea of the differences between blunt

and penetrating trauma (see Chapter 1, Combat

Trauma Overview, in this textbook, and The Medical

Consequences of Conventional Warfare: Ballistic, Blast,

and Burn Injuries, an earlier (1991) volume in the

Textbook of Military Medicine series). In addition,

anesthesia providers should thoroughly review the

areas of difficult intubations, hypovolemic shock,

hypothermia, muscle relaxants in casualties with

burns or traumatic injuries, and massive transfusion procedures.

One specific area of training for the field has been

particularly problematic in the past decade: realis-
Combat Anesthesia Overview

49

tic training with field anesthesia machines.

Ohmeda’s 855A field anesthesia machine (FAM)

and its Universal portable anesthesia circuit (PAC),

as they are marketed, do not meet all current safety

requirements for routine use in CONUS in peacetime. This complex issue has been studied at great

length at the highest levels of the U.S. Army Medical Corps’ military preparedness community, and

a workable solution is now being formulated.

Under the guidance of Lieutenant Colonel D. M.

Anderson, Consultant in Anesthesiology to The

U.S. Army Surgeon General, training sites at Walter

Reed Army Medical Center, Washington, D. C.,

Womack Army Medical Center, Fort Bragg, North

Carolina, and Brooke Army Medical Center, San

Antonio, Texas, have been established to provide

carefully monitored instruction in the use of the

draw-over device. Numerous machine monitors

are added to the PAC when it is used in this setting.

The patients are young and healthy, and their surgery does not involve the thorax, abdomen, or head

(ie, they are in American Society of Anesthesiology

[ASA] category I). An instructor, designated by the

Consultant in Anesthesia to the U.S. Army Surgeon

General, is either in the operating room or is immediately available. This augmented “teaching” PAC

is always used in conjunction with a standard, modern anesthesia machine, which is positioned for

immediate use, plugged in, and turned to the “standby” setting in case any need arises for additional

support. As of January 1995, more than 45 operations using this draw-over teaching system had

been performed at Walter Reed Army Medical Center and more than 250 at Womack.1 The Joint Medical Readiness Training Command has developed a

curriculum for instruction with the PAC and will

implement this program in conjunction with the

anesthesia services of Brooke Army Medical Center

and Wilford Hall.

A protocol that will allow military anesthesia

providers the opportunity to gain experience with

the 855A FAM is also being developed. Carefully

controlled conditions that involve both upgrading

the machine-monitor capabilities, certification of

instructors, and presence of standard back-up devices are being worked out to enable teaching the

use of the 885A FAM. Two preliminary cycles of

885A FAM training have already occurred at Walter

Reed, and an army-wide program should be in

place by the end of 1995. With the growing emphasis on readiness, opportunities to train under realistic conditions can be expected to improve steadily

in the coming years.

Training the Team After Deployment

Anesthesia providers tend to lead highly specialized, rather isolated, professional lives in peacetime. It is necessary to change this pattern during

deployment. To a degree unequaled in any other

aspect of medicine, trauma care is a team effort.

Members of the anesthesia group must be prepared

to shoulder some of the responsibility for planning

and training the team to respond to mass casualty

events. As a key member of the casualty-receiving,

triage, and stabilization teams, as well as of the

operating room’s main effort, the military anesthesia provider’s expertise, training, and problem-solving abilities are among the deployed hospital’s most

valuable assets. Anesthesia providers tend to become involved at every point in the care of casualties, from the initial assessment on the helipad to

the transfer onto C-141s for out-of-theater evacuation. Because of this latitude of involvement, anesthesia providers are ideally placed to understand

exactly what does and does not work in their team’s

efforts. Combat zone hospitals are not the place for

a reticent specialist; everyone with the skill and the

authority has the responsibility to participate fully

in both planning and training.

It is incumbent on anesthesia providers to take a

proactive position in the effort to train the nonmedical members of the field hospital. Not only

must basic skills be effectively taught, but all members of the unit must understand that their individual efforts are vital to the mission of caring for

wounded soldiers. Anesthesia providers have great

skill and experience in the areas of transport, intravenous access, monitoring for vital signs, and airway support. These basic skills must be rapidly

imparted to personnel without much predeployment

day-to-day exposure to patient care. An involved,

supportive, leadership/instructor style is well suited

to the field environment. By contrast, the more withdrawn, caustic style that is characteristic of many

teaching institutions is not effective in this setting

and is likely to be misunderstood.

Level 1 trauma centers in CONUS have the luxuries of large ancillary service staffs and a virtually

unlimited supply of reinforcements. This is usually

not the case with deployed units. When field hospitals go into a crisis-response mode, reinforcements

will come from the nonmedical areas of the unit

(motor pool, mess hall, laundry and bath, etc).

During overseas mass casualty exercises, for example, patient transport personnel are usually

drawn from those sections of the deployed unit that
Anesthesia and Perioperative Care of the Combat Casualty

50

are not involved directly with patient care. During

high-volume trauma incidents, the diesel mechanics and cooks assigned as litter bearers will suddenly become key members of the trauma team. It

will be up to them to establish and maintain orderly, safe, and efficient patient flow under conditions that are fatiguing, uncomfortable, and sometimes hazardous. The effectiveness of these soldiers

in the early phase of a mass casualty situation

can set the tone, for better or worse, of an effort that

may go on nonstop for days. Their training, no less

than that of the medical officers and nurses, must

be thorough and inclusive. They must be quite

comfortable with the appropriate techniques for

safely transferring patients to and from helicopters,

fixed-wing aircraft, tracked vehicles, and field

ambulances. For example, the off-loading and

transport of a litter patient with an unstable cervical spine from a Huey helicopter, at night, under

black-out conditions, is not only difficult but is

also quite dangerous to all concerned. Litter bearers must also be able to deliver casualties to the

minimal care, delayed, and expectant triage category areas without interfering with flow to and

from the emergency tent and the operating room.

The correct pathways through the tents, ISO shelters, and other structures that make up the maze

of a field hospital must be learned thoroughly

before the first emergency. Seemingly minor details—such as which entrances must be entered

with the litter headfirst and which feetfirst—can

take on immense importance in crises where every

minute counts.

Not all postdeployment instruction involves taking personnel out of their primary specialties and

teaching them new skills. Some of the most important training in this period entails expanding existing capabilities and increasing the breadth and depth

of the individual soldier’s knowledge. For example,

during many of a deployed hospital’s most important functions, the unit’s radio operators become

vital communications links between field medics,

evacuation vehicle crews, and members of the emergency and operative services. The radio operators

must be taught to understand and accurately record

field telephone and radio messages from medics,

flight nurses, and medical officers. In addition,

these soldiers become an important part of the patient care delivery system, as they are trained to

extract accurate information from helicopter crews

bringing casualties to your facility. Although there

are well-established, detailed, communications formats for medical evacuation, circumstances on the

ground or in the air may, understandably, distract

the air crews or soldiers at the scene. The initial

radio transmission may indicate little more than the

fact that casualties are coming to your helipad.

Well-trained radio operators can usually overcome

the difficulties involved with intermittent or garbled

transmissions and at least determine such basic

information as the number of wounded, the anatomical sites of injuries, and whether all patients are

conscious or at least breathing. Enlisted personnel

in the Signal Corps are quite bright; they are well

motivated and tend to have excellent judgment. If

properly trained and encouraged, they can become

great assets to the medical-care efforts. If you

conscientiously help them expand their capabilities, they will make your unit’s trauma-receiving

efforts much more effective.

In times of crisis, almost everyone in your unit

will play a direct or immediate support role in the

care of casualties. As these two examples have

demonstrated, nonmedical members of the field

hospital play a key part in achieving a successful

outcome during such emergencies. Because these

soldiers will be asked to perform vital jobs outside

their primary field of expertise with minimal supervision, they must know their jobs inside and out.

To the extent possible, units should train together prior to deployment. At the time of this

writing (1995), vast strides are being made in improving the U.S. Army Medical Department’s ongoing field training. However, there is no way to anticipate exactly either the environment or the clinical

situations you will face. Perhaps more importantly,

the inevitable professional isolation and heightened degree of individual responsibility cannot be

realistically duplicated in stateside training exercises. For that reason, a planned series of exercises

of graduated magnitude, pace, and complexity

should begin as soon as possible after arriving incountry. These drills should begin within a few

days of arrival at the facility outside CONUS and

should continue until the teams have been through

more than one real situation. Even if a full-scale

mass casualty situation occurs on the first day, you

should still go through a measured training cycle

during the ensuing weeks, because it is difficult to

make on-the-spot corrections or to try new ideas

during a real emergency. The training sessions

should begin as walk-throughs and proceed to more

complex, realistic drills. Moulage is probably not

worth the effort in this setting, but drills involving

moving soldiers in combat gear on litters all the way

through the system—from aircraft and vehicles to
Combat Anesthesia Overview

51

the various destinations in the hospital—are essential. There should be no unannounced drills in

hostile-fire environments. It should be made abundantly clear to all concerned that everything except

announced practice exercises are the real thing and

must be responded to without hesitation.

One of the truisms regarding trauma medicine in

remote environments is this: if your team members

have not worked on live, bleeding patients, they do

not know whether they can perform effectively or

not. U.S. Army field hospitals are sometimes deployed weeks or months before hostilities begin. In

this period of quiet before the storm, the worst

position to take is one of passive inaction. If the

political, tactical, and logistical situations allow,

the unit should accept injured coalition soldiers or

patients from the indigenous population at a steady,

controlled pace. Field hospitals, no less than tactical units, need to perform the equivalent of live-fire

exercises. The logistical cost of doing at least one

emergent surgical case every other day is small

when compared to the dramatic increase in performance that will result from a sustained effort at improving combat casualty care.

Special Problems With Blood and Blood Products

As a part of the surgical team, you will be one of

your unit’s most important subject-matter experts

on blood utilization. As such, you must be aware of

the basic problems that face deployed field hospitals and help to develop plans to overcome these

difficulties. It is in this area, perhaps more than any

other, that the medical environment of the battlefield differs from that of civilian hospitals in the

United States. Platelets cannot be stored for more

than 48 hours, and it is quite likely that this component of blood therapy will not be available to you in

many remote locations. A field plasmapheresis unit is

under development but is not currently in distribution. This means that your unit must either be able (a)

to reliably acquire platelets expeditiously in any

emergency, (b) to use whole blood as a source of

platelets, or (c) to accept a certain number of otherwise-preventable lethal exsanguinations. Fresh,

whole-blood transfusions from local donors are not

commonly performed in CONUS in peacetime, and

therefore most physicians have some reservations

about the process. Most field hospitals will not be

able to screen for hepatitis viruses, human immunodeficiency virus, cytomegalovirus, or malaria in

a timely fashion. The use of fresh, whole blood,

then, will involve some unavoidable risks.

Fresh frozen plasma may also be difficult to use

under some field conditions. During my own deployment to Somalia (1993–1994), the usability of

fresh frozen plasma was seriously affected by two

technical problems: the field warming unit took 45

minutes to thaw the fresh frozen plasma, and 50% of

the bags ruptured during this procedure.

It is crucial that military physicians involved in

trauma care overseas understand the essentials of

the supply system that delivers packed red blood

cells to their facility. A thorough comprehension of

the routine delivery schedules and emergency replacement options is necessary so that appropriate

stock levels may be maintained. To be able to

respond effectively to mass casualty situations,

stocks of blood and blood products must be kept at

high levels. A single firefight or an incident such as

a landmine being detonated by a truck loaded with

soldiers can necessitate the expenditure of up to 50

units of blood. Conversely, during conflicts characterized by sporadic fighting, weeks or months may

go by with little or no demand for blood or blood

products. A high level of resource wastage due to

outdating can be anticipated in this setting. Nevertheless, these periods of relative inactivity and the

associated waste of a scarce and valuable resource

should not lead to a lowering of stock levels. Unless

the mission, the number of troops supported, or the

essential nature of the conflict change, the deployed

field hospital’s state of readiness should not be

downgraded in response to periodic variations in

casualty rates.

It is customary for the chief of the laboratory

services to publish a daily accounting of the number

and type of units of blood products on hand. It may

be beneficial to post this information in the operating room as soon as it is published. One of the most

important reasons for the unit to become active in

the management of trauma early in the deployment is

to allow the medical, laboratory, and logistical elements concerned with blood utilization to learn to

function together smoothly. Experience with administering massive transfusions in remote locations

will also help medical personnel resist attempts by

well-meaning logisticians to reduce blood stockage

levels based on temporary declines in usage.

Essentials of Readiness: Equipment, Training,

and Attitude

At least one operating room site should be set up

for major trauma at all times. This includes an

anesthesia machine, airway equipment, a well-
Anesthesia and Perioperative Care of the Combat Casualty

52

stocked cart, a functioning cart top (with resuscitative drugs drawn up and labeled), provisions for

rapidly delivering blood and warmed fluids, electronic monitors, and extra supplies. On a broader

scale, each hospital unit must establish some method

for acquiring and storing the medical supplies necessary to support the dramatic surges experienced

during mass casualty situations. The members of

the anesthesia service must aggressively identify

and solve all problems associated with critical supply items before the emergencies begin. Because

the capability for immediate resupply is so limited,

the involved medical specialists must take the responsibility of determining both their future needs

and their current stock levels. For example, as the

medical treatment facility’s subject-matter experts

on resuscitation, it is incumbent on the anesthesia

provider to understand how much crystalloid solution must be readily at hand. In these instances, the

training and operations officer (the S-3) is a valuable source of information. For example, if it were

learned that an armored brigade had been attached

to the division being supported by the field hospital, the training and operations officer should be

able to provide a rough estimate of the increase in

the number of burned casualties that could be expected in the near future. This information, and a

quick inventory of the unit’s intravenous fluid

stocks, should allow for a reasonable assessment of

the hospital’s ability to support its expanded mission.

Obviously, key personnel must be in as high a

state of readiness as is their equipment. Unless a

unit is blessed with an extraordinary level of communication and transportation, at least one anesthesia provider should be in the compound at all

times. A routine establishing which member of the

anesthesia team will report to the emergency tent

and which members will report to the operating

room should be set and practiced until responses to

incoming trauma are automatic.

Preparing for the Worst Case

Combat-related casualties and fatalities are quite

rare among members of the Medical and Nursing

Corps, but they do occur. All deployment plans

should, at some point, be able to answer this question: Who is going to take care of the hospital’s

doctors and nurses if they get hurt? Plans should

involve both interhospital contingencies and arrangements with other U.S. or coalition medical

forces. The advisability of all anesthesia care providers or all surgeons or both traveling together in

the same vehicles or aircraft should be carefully

considered. Whether or not all members of the

operating room team should bunk in the same area

is also an issue worth considering in some environments.

Problems of Morale

As numerous afteraction reports have noted, the

aspect of preparedness most difficult to maintain is

probably the psychological one. The prolonged

tedium between emergencies that becomes a part of

almost every deployment seems to be especially

damaging to the morale of medical department

personnel. Physicians and nurses tend to be aggressive and problem-oriented, and they often find the

lack of immediate challenge especially hard to bear.

This is only one more reason to urge deployed

facilities to stay as busy as the tactical and logistical

situation will allow. Equipment, skills, attitudes,

and systems quickly deteriorate in the vacuum of

idleness. If the fighting dies down, consider offering your services to the special forces or civil affairs

teams in the theater. An aggressive team of medical

personnel can find a patient population in almost

any environment. The importance of a smoothly

operating trauma response team’s maintaining its

clinical skills cannot be overemphasized. Anesthesia providers, who always have the rank of at least

captain, have a central position in most of the meaningful activities of the team. The influence of the

morale of the surgical team on that of the entire

hospital is profound; use your influence and authority to help the team stay busy and enthusiastic.

Preparing for the Future

Clearly, it is impossible to identify, in anything

more than the most general terms, the nature of the

operations the U.S. military’s medical services will

support in the future. Nor is it possible to predict

what new technologies and therapeutic interventions will be introduced into the world of clinical

anesthesia in the coming decade. What, then, must

we do to prepare for the future?

In all the considerations of wound ballistics,

evacuation strategies, plans, training, and logistics,

it is possible to forget that what the U.S. Army really

expects of its medical officers is that they take the

best possible care of soldiers and their families. The

single most important element in preparation for

treating casualties of war is a strong graduate medi-
Combat Anesthesia Overview

53

cal education program. Good residents and students make good doctors and nurses. To be most

effective, medical personnel should be made aware

of the field hospital environment, the nature of war,

and the techniques of care of masses of casualties.

However, the drive to educate doctors and nurses

to the realities of field medicine must be balanced

by the clear understanding that the most important aspect of readiness is the acquisition and

sustainment of clinical proficiency. Particular facets of strategy, climate, and geography may force

medical personnel to modify their practices to accommodate the realities of any given deployment,

but achieving the highest level of care possible

under the circumstances should be the deployed

hospital’s unwavering goal.

REFERENCE

1. Reynolds P. Lieutenant Colonel, Medical Corps, US Army. Personal communication, January 1995.
Airway Management

55

Chapter 3

AIRWAY MANAGEMENT

RICHARD B. HECKER, D.O.*; AND CHARLES P. KINGSLEY, M.D.†

INTRODUCTION

FUNDAMENTALS OF AIRWAY MANAGEMENT

Airway Obstruction

Goals of Airway Management

Patient Evaluation

BASIC EQUIPMENT FOR AIRWAY MANAGEMENT

Oxygen Therapy

Oxygen Adjuncts

Airway-Management Adjuncts

PLACEMENT OF AIRWAY DEVICES

Airway Classification

Anesthetizing the Airway

Specific Nerve Blocks

Nasotracheal Intubation

Orotracheal Intubation

Rapid-Sequence Induction of Anesthesia

COMPLICATIONS OF AIRWAY MANAGEMENT

Regurgitation and Aspiration

Management of Pulmonary Aspiration

MANAGEMENT OF THE FAILED INTUBATION

SPECIAL AIRWAY-MANAGEMENT CONSIDERATIONS

Head Injury

Cervical Spine Injury

Eye Injury

DIRECT INJURY TO THE AIRWAY

Maxillofacial Injury

Laryngeal and Tracheal Injury

Thermal Injury

SUMMARY

*Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Brooke Army Medical Center, Fort Sam Houston, Texas; Clinical

Assistant Professor of Anesthesiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7834, and

The Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799

†Formerly, Lieutenant Colonel, Medical Corps, U.S. Army; Anesthesia and Operative Service, and Chief, Department of Clinical Investigation,

Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200; currently, Associate Professor of Anesthesia, The Milton S. Hershey

Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
Anesthesia and Perioperative Care of the Combat Casualty

56

The most gravely wounded casualties—those

dying from exsanguination or severe brain injury—

will most likely outnumber those seen with direct

airway trauma. The major indication for emergency airway management is found in the group

with severe head injuries. WDMET data indicate

that 0.7% of all casualties who required immediate

airway intervention were in this category; these

data also show that 10% of casualties treated in

medical facilities arrived in a state of hypovolemic

shock.3 Rapid intravenous fluid administration will

temporarily reverse shock in most cases, but the

treatment of severe hypovolemic shock by rapid

fluid resuscitation is facilitated by early airway

intubation and mechanical ventilation. These casualties may increase the total percentage of cases in

whom immediate airway management is necessary.

Finally, WDMET data indicate that 3.2% of combat casualties arrived alive from the battlefield with

difficult breathing due to chest wounds. One half of

these casualties had a tension pneumothorax and

the remainder had sucking chest wounds.3 Tension

pneumothorax can initially be managed by tube

thoracostomy alone, but disruption of the chest

wall will usually require tracheal intubation and

mechanical ventilation. For the purpose of this

discussion, if we exclude (a) those casualties who

will require ventilatory assistance due to postoperative respiratory insufficiency and (b) those suffering from lung damage due to blast overpressure,

inhalational injury, or chemical agent exposure,

then possibly 5% to 10% of the total combat casualty

population entering the military medical system

will be candidates for immediate airway management.

In 1980 in the United States alone, 105,000 fatalities and 10 million disabling injuries occurred as a

result of accidents.4–6 In the civilian experience, as

in the military, airway management is the initial

step in resuscitating victims suffering from trauma

or sudden cardiac death.7 Although few data exist

regarding the direct impact of appropriate initial

airway management on the survival of trauma victims, failure to provide timely emergency airway

management in parturient and surgical patients is a

leading cause of morbidity and mortality.8–11 The

establishment of trauma centers that foster rapid

and appropriate airway management in the

prehospital phase of care appears to have a favorable effect on patient outcome.12,13

Untreated airway obstruction will result in death

from cerebral anoxia within several minutes. Fortunately, most causes of airway obstruction can

easily be reversed. Although massive exsanguination due to cardiac or aortic injury is not

amenable to first-aid measures, the resolution of

airway compromise may be lifesaving in the field.

Combat casualties who will require airway interventions can be grouped into four categories:

1. those whose direct trauma to the airway

causes obstruction;

2. the severely wounded casualty (eg, with

an exsanguinating injury or in a comatose

state) who needs a secure airway;

3. those with impending or known respiratory failure due to blast or inhalational

injury, exposure to chemical agents, or

postinjury or postoperative respiratory insufficiency; and

4. the casualty who needs a controlled airway during the administration of anesthesia for surgery.

In the military, casualties in the last category will

certainly constitute the major source of airway interventions, as surgery for most combat injuries

will be performed under general anesthesia. Airway management in this setting will be performed

by trained anesthesia providers. Most combat casualties arriving at definitive medical facilities will

not require immediate operation, and there will be

time for a planned approach for airway control.

The number of casualties that comprises the first

three categories—those who require emergency airway intervention in the field—is not large. In fact,

the data assembled during the Vietnam War by the

Wound Data and Munitions Effectiveness Team

(WDMET) reveal that only 1.3% of combat casualties who arrived at medical facilities directly from

the battlefield required emergency airway management. Only one half of these casualties (0.6% of the

total) suffered from a traumatic airway injury.1

 Data

collected nearly 30 years later, during the 1991

Persian Gulf War, demonstrated only a 0.4% incidence of airway obstruction due to trauma.2

 On

review of the WDMET data, it is impossible to

determine the exact number of soldiers who died on

the battlefield due to acute airway obstruction prior

to medical intervention, although autopsy results

suggest that this occurrence was uncommon.3

INTRODUCTION
Airway Management

57

Newcomers to military medicine must appreciate this fundamental fact: the mechanisms of injury

are different in civilian and military trauma. Most

civilian trauma is caused by blunt injury, while

most military battlefield injuries are caused by penetrating missiles. Therefore (owing to the high

lethality of penetrating missile wounds of the head,

chest, and neck), the percentage of casualties who

require lifesaving airway intervention is lower than

the percentage seen in civilian accident victims.

FUNDAMENTALS OF AIRWAY MANAGEMENT

The term airway is customarily used in two senses:

the anatomical (ie, to denote any part of the respiratory tract through which air passes during breathing), and the operational (ie, to denote a device for

correcting obstructions to breathing). This semantic imprecision is regrettable because it may confuse

the uninitiated, but the usage is well established

and we will not attempt to introduce new nomenclature here.

Airway Obstruction

The Medical Service of the Army of the Soviet

Union has published data from World War II that

help us appreciate the anatomical basis for upperairway obstruction that is seen in combat casualties

(Table 3-1).14 It appears that almost all classes of

injury had a penetrating component as the etiology

of the obstruction. Direct airway injury and maxillofacial blunt trauma are also causes. (The nature

and detailed management aspects of maxillofacial

injury are discussed in Chapter 18, Injuries to the

Face and Neck.)

Many of the battle casualties who require immediate airway intervention will not survive to be

evacuated from the site of injury to the field hospital level without first receiving airway control. For

these casualties, airway intervention must take place

in the first or second echelons of care, where military anesthesia providers are unlikely to be present.

Therefore, medics, physician assistants, and physicians providing care at the first and second echelons

must be able to provide early airway management.

Medical personnel trained in the provision of anesthesia and airway control will be available at the

third and fourth echelons of care. The interventions

chosen to reverse airway obstruction and to provide definitive airway control will, to some extent,

depend on the echelon of care (Table 3-2). Nevertheless, simple maneuvers such as the head tilt and

the chin lift, which are discussed later in this chapter, are universally applicable (Figure 3-1). Not

only medical officers but also physician assistants

within the first and second echelons should be able

to use a bag-valve-mask device, place an endotracheal tube, and be familiar with performing an

emergency surgical airway intervention such as a

cricothyroidotomy. Teaching of these life-saving

techniques should be part of any formalized medical training program for these providers.

Goals of Airway Management

The aims of airway management are to (a) relieve

airway obstruction, (b) prevent pulmonary aspiration, and (c) serve as an adjunct for therapeutic

intervention. The initial and foremost goal of airway management is to ensure relief from obstruction. Obstruction of the upper airway can, in most

instances, be dramatically relieved by the simple

maneuvers of head tilt and jaw thrust. Cautious

sweeping of the oropharynx with the fingers may

assist in locating and removing foreign material,

teeth, dentures, food, or vomitus. Suctioning of the

oropharynx allows for the removal of blood, secretions, and regurgitated gastric contents that may

impede spontaneous or assisted ventilation.

TABLE 3-1

ASPHYXIATION WITH FACIAL AND JAW

WOUNDS IN THE RUSSO–GERMAN

WAR, 1941–1945

Injury Frequency (%)

Prolapse of the tongue into the 40

pharynx due to structural damage

to the mandible

Blockage of upper airway by 29

damaged detached oropharyngeal

tissue

Compression of the trachea as a result 23

of edema or hematoma in the neck

Displacement of the glottis/larynx by 5

surrounding soft tissue

Aspiration of blood and vomitus 3

Data source: Rehwald G. Organization and Tactics of the Medical

Service. Berlin, German Democratic Republic: Military Press,

GDR; 1973: Table 3.10.
Anesthesia and Perioperative Care of the Combat Casualty

58

TABLE 3-2

AIRWAY MANAGEMENT BY ECHELON

Location Medical Personnel Principal Indication for Airway Control

First and second echelons Not anesthesia-trained Direct upper-airway trauma

(prehospital levels) Exsanguination

Comatose state

Third echelon and above Anesthesia-trained Adjunct to general anesthesia and

(hospital levels) emergency perioperative care

The prevention of pulmonary aspiration of blood,

foreign material, or regurgitated gastric contents is

the second goal of airway management. The normal protective airway reflexes may be obtunded

due to intracranial injury, loss of consciousness,

hypoxemia, hypercarbia, or hypovolemia-induced

hypotension. Pulmonary aspiration leading to

pneumonitis is associated with a very high morbidity, and the mortality rate seen with respiratory insufficiency in these patients may be as high as 50%.15

The maintenance of adequate ventilation and gas

exchange is the third goal of airway management.

Ideally, this is best accomplished by endotracheal

intubation. Casualties who present with injury to

the central nervous system need not only airway

protection but, to maintain a normal acid–base status, may also require mechanical ventilation to assure adequate oxygenation and to eliminate carbon

dioxide. Furthermore, control of the airway may

allow for hyperventilation to ensure that hypocarbia

is used as a temporary therapeutic modality to

lower cerebral blood flow and to decrease intracranial pressure in the casualty with acute head injuries. Cervical spine injuries may be associated with

spinal cord injury, causing respiratory weakness or

paralysis that requires mechanical ventilation.

Trauma to the thoracic area, with rib fractures and

underlying cardiac or pulmonary contusions, may

also require ventilatory assistance. Finally, the

pneumonitis resulting from the pulmonary aspiration of gastric contents is best managed by mechanical ventilation and the application of positive endexpiratory pressure (PEEP).

Patient Evaluation

Assessment of the airway in the combat casualty

is an ongoing process. The initial steps in airway

management should occur simultaneously with the

initial evaluation of the injuries. If supplemental

oxygen therapy is available, it should be provided

to trauma victims during the initial assessment.

Airway patency should be the first priority of the

patient evaluation. Signs of airway obstruction

include stridor, inability to phonate, nasal flaring,

supraclavicular and intercostal muscle retractions,

and paradoxical abdominal muscle contractions. If

airway obstruction is present, immediate steps must

be taken to relieve the obstruction. Once the adequacy of the airway is established, the remainder

of the injury evaluation can be completed.

Simple observation and examination of the patient are poor indicators of the adequacy of oxygenation and ventilation. If resources are available, the

assessment of arterial or venous oxygen saturation

may be helpful in those cases where adequate oxygenation is a concern. A complete physical examination of the patient should be made, in conjunction

Fig. 3-1. Soft-tissue obstruction (a) relieved by head tilt

and chin lift (b). Reprinted with permission from

Cummins RO. Textbook of Advanced Cardiac Life Support.

Dallas, Tex:American Heart Association; 1994: Chap 2: 2-1.

a

b
Airway Management

59

with other medical personnel, to thoroughly appreciate the extent of the patient’s injuries. Examination of the head may reveal scalp lacerations and

skull fractures, particularly in the occipital region.

These injuries may not be detected during the initial

assessment due to their location and may become

apparent as the head is manipulated for airway

management. If head injuries are found, the technical approach to airway management may have to be

altered. Bleeding head wounds may be an unappreciated major cause of hypovolemia. Any casualty

who has been unconscious, becomes unconscious,

or develops an altered mental status should be

assumed to have an intracranial injury and should

be treated appropriately. The presence of ocular

injuries may also lead to an alteration in airway and

anesthetic management.16

Although the patency of the airway may have

been judged to be adequate during the initial evaluation, continuous and careful patient observation

must occur if medical personnel are to recognize

changes in mental status or ventilatory ability. These

changes can occur in an insidious fashion. All

trauma victims who are conscious and complain of

cervical pain, those who present with motor or

sensory deficits of any extremity, and those who are

unconscious must be presumed to have an injury to

the cervical spine. These casualties should be treated

with cervical immobilization with a rigid collar and

back board until radiograph evaluation of the cervical spine, to include visualization of C-7, is performed.17,18

Injuries to the airway can be divided anatomically into supraglottic, glottic, and subglottic trauma.

Supraglottic injuries (eg, facial fractures) with resultant hemorrhage may be a cause of significant

airway obstruction. Glottic injuries may cause

stridor and the inability to phonate; casualties with

such injuries present with severe respiratory obstruction due to edema or hemorrhage. Subglottic

injuries may cause obstruction and can be associated with subcutaneous emphysema that may involve the entire head, thorax, and abdomen, which

further complicates airway management. It is paramount that these injuries be detected prior to the

insertion of airways, as attempts at endotracheal

intubation may be futile, further worsen the airway

situation, and delay the establishment of a definitive surgical airway. As most combat casualties

have penetrating missile wounds as the mechanism

of their injury, an entrance wound in the face or

neck will suggest the likelihood for airway compromise that demands surgical intervention.

The presence of a penetrating missile wound to

the chest must alert the medical provider to the

possibility of lower-airway injury. Lower-airway

injury may not be as obvious in the setting of blunt

trauma to the chest with possible resultant rib fractures, flail chest, pneumothorax, hemothorax, or

pulmonary contusion. The chest should be carefully inspected for asymmetrical motion with ventilation, and for decreased or absent breath sounds.

Hypotension seen with distended neck veins is a

result of tension pneumothorax compromising

venous return to the heart. Needle thoracostomy

(with an 18-gauge or larger needle) in the

midclavicular second intercostal space can temporarily decompress the tension pneumothorax until

a tube thoracostomy can be placed in the T-5 anterior axillary line area. A persistent air leak from a

thoracostomy tube may indicate a tracheal or bronchial injury. Chest radiographs should be obtained

to detect occult pneumothorax or hemothorax, rib

fractures, pulmonary contusion, or to appreciate a

widened mediastinum, which suggests injury to the

great vessels.

The abdomen, genitourinary system, and extremities must also be examined. Injuries to these areas

have only minimal impact on initial airway management. However, it should be appreciated that

blood loss in these areas may contribute to profound hypovolemia that necessitates later surgical management requiring airway placement for

anesthesia.

BASIC EQUIPMENT FOR AIRWAY MANAGEMENT

for each casualty and to assemble the proper equipment before attempting to secure an airway. Most

importantly, should the original plan prove unsuccessful, all airway-management plans should include several additional approaches.

Standard equipment necessary for emergency

airway management is listed in Exhibit 3-1. Depending on the echelon of care that will provide

facilities for the management of the airway, addiThe successful approach to airway management

requires a thorough understanding of the underlying respiratory pathology, hypoxemia, hypercarbia,

or airway obstruction before the selected therapy is

applied. To select the correct approach to a particular airway problem, this knowledge must be coordinated with an understanding of the available techniques and airway-management equipment on

hand. It is crucial to formulate an individual plan
Anesthesia and Perioperative Care of the Combat Casualty

60

EXHIBIT 3-1

EQUIPMENT NECESSARY FOR

EMERGENCY AIRWAY MANAGEMENT

Laryngoscope with blades of various sizes and

shapes

Endotracheal tubes of various sizes

Endotracheal tube stylet

Oral and nasal airways

Face masks of various sizes and configurations

Tonsil-tipped suction handle and suction source

Bag-valve-mask device with a self-inflating

reservoir and oxygen coupling

Oxygen source and tubing

Nasogastric tubes of various sizes

Emergency drugs

Adapted with permission from Grande CM. Airway

management of the trauma patient in the resuscitation

area of a trauma center. Trauma Q. 1988;5:30-49.

ume of the patient’s nasopharyngeal anatomical

reservoir.19 The administration of oxygen by this

method is effective in mouth breathers because the

airflow in the posterior pharynx produces a Bernoulli effect that entrains reservoir oxygen located

in the nasopharynx. Each liter of supplemental

oxygen that is provided can potentially raise the

FIO2 by 0.03 to 0.04 (3%–4%), although the ceiling

flow rate is approximately 6 L. Using nasal prongs,

the FIO2 can therefore be enriched up to 0.45 (45%

oxygen).20 The use of oxygen flow rates greater than

6 L/min wastes resources, serves to be a source of

discomfort to the patient, and may dry secretions.

A face mask must be used to achieve further

increases in FIO2. Face masks come in four configurations: simple, partial rebreathing, nonrebreathing,

and air-entrainment (eg, Venturi) masks. Simple

face masks provide an FIO2 from 0.35 to 0.60 at a flow

rate of 5 to 8 liters of oxygen per minute. In adults,

flow rates less than 5 L/min with this type of mask

may allow partial rebreathing of exhaled gas. As

there is little difference in the maximum FIO2 that is

provided by either nasal cannulae or simple face

masks, the choice of using one or the other becomes

a matter of patient comfort or preference.21

Partial and nonrebreathing masks contain an

oxygen reservoir bag and allow for the delivery of

an FIO2 of 0.8 to 1.0, with high flow rates greater than

10 L/min. In the partial rebreathing system, the

proper adjustment of oxygen flow allows the oxygen-rich, dead-space portion of the tidal volume to

refill the reservoir bag. This constitutes 30% of each

tidal-volume breath and, in effect, decreases the

required gas flow by one third. Nonrebreathing

systems are less efficient but allow for maximum

FIO2 delivery. The rebreathing mask contains oneway valves that prevent rebreathing and entrainment of ambient air into the mask.

Air-entrainment masks employ jet mixing of oxygen with ambient air utilizing the Venturi principle

to provide a fixed FIO2 rate. Oxygen delivery can be

specifically selected in an FIO2 range of 0.24 to 0.50.

It is important to appreciate that a specific Venturi

setting must be matched to a specific oxygen flow

rate to obtain the desired FIO2. For the application

of an FIO2 in the range of 0.28 to 0.40, a face tent is an

alternative to a face mask. In a cooperative patient,

a tent is often better tolerated than a mask.

Airway-Management Adjuncts

Casualties suffering from hypoventilation due to

airway obstruction may require assistance ranging

from simple airway maneuvers to endotracheal

tional equipment and emergency adjuncts may be

available.

Oxygen Therapy

The management of hypoxemia is aimed at raising the arterial partial pressure of oxygen (PaO2).

The arterial oxygen content of blood (CaO2) can be

raised by fully saturating hemoglobin and increasing the dissolved oxygen in the blood to maximize

its delivery to the tissues. Oxygen therapy allows

time for treating the underlying cause of hypoxemia—whether from anemia, hypovolemia, sepsis,

pulmonary edema, or cardiac failure. Supplemental oxygen therapy is simple to provide, has minimal short-term risk to the patient, and, because it is

so simple, is quite easy for medical personnel to

forget to deliver in a crisis.

Oxygen Adjuncts

The simplest method of administering oxygen is

via nasal cannulae. The maximal fraction of inspired oxygen (FIO2) that can be achieved depends

on the oxygen flow rate, the patient’s minute ventilation, the amount of inspiratory flow, and the vol-
Airway Management

61

intubation and controlled ventilation. The simplest

method for airway control entails extending the

neck (ie, the head tilt) and elevating the mandible in

a forward manner (ie, the chin lift). This maneuver

establishes a patent airway by displacing the mass

of the tongue away from the posterior pharynx. In

the comatose casualty, the loss of muscle tone allows the tongue to fall posteriorly against the pharyngeal tissues and therefore obstruct the airway.

This is the most common cause of airway obstruction, and it is easily alleviated. However, cervical

extension is contraindicated in patients with known

or suspected cervical spine injury, and the chin-lift

alone should be attempted with these casualties.

Commonly available airway-management adjuncts may also be used to establish a patent airway.

Stiff oropharyngeal airway devices are available in 40-

to 100-mm sizes, with the 80- or 90-mm size being

acceptable for most adults. The use of these airway

devices may cause gagging in awake patients due to

stimulation of the pharyngeal structures. Softer

nasopharyngeal airway devices are available in

French (F) catheter sizes; F28 to F34 are usually

placed in adults. They may cause discomfort or

epistaxis on insertion, but partially awake patients

tolerate them somewhat better than oral airway

devices. Nasopharyngeal airway devices can be

placed bilaterally if needed (Figures 3-2 and 3-3).

Fig. 3-3. Soft-tissue obstruction relieved by head tilt and

the placement of a nasopharyngeal airway. Reprinted

with permission from Cummins RO. Textbook of Advanced

Cardiac Life Support. Dallas, Tex: American Heart Association; 1994: Chap 2: 2-2.

Bag-valve-mask devices may be used to improve

oxygenation and ventilation until a more permanent airway can be secured. The face masks that

may be fitted to these devices come in a variety

of sizes and configurations to better conform to

different facial structures. All commercially available bag-valve-mask systems are provided with

a standard 22-mm connector that attaches to a

standard 15-mm connector fitting, which is found

on replaceable masks and endotracheal tubes. The

reservoir bags on these devices are either selfinflating or require a flow of oxygen to fill them.

The stiffer, self-inflating bag can be used with room

air to fill the reservoir, and it comes with an oxygeninlet port if oxygen supplementation is needed. The

use of oxygen allows for an FIO2 of up to 1.0 with

these devices. The bag-valve-mask devices are

commonly available in emergency areas and are

more easily used by providers who are relatively

untrained in airway management. A major disadvantage of this type of device is that little information concerning pulmonary compliance can be obtained by the “feel” of the reservoir bag. These

systems have a one-way valve that prevents

rebreathing of expired gas. A specialized bag-valvemask arrangement that is favored by anesthesiatrained personnel is called the Jackson-Rees modification of Ayre’s T-Piece, which is essentially a

modified Mapleson E circuit.22,23 This type of bagvalve-mask device has an adjustable exhaust valve

that allows for a “feel” of the pulmonary compliance. A disadvantage of this type of device is that

a fresh-gas flow is required to inflate the bag, and

the exhaust valve must be properly adjusted to

prevent the inadvertent application of PEEP. Some

degree of rebreathing of exhaled gas may occur at

low gas-flow rates.

Fig. 3-2. Soft-tissue obstruction relieved by head tilt and placement of an oropharyngeal airway. Reprinted with permission

from Cummins RO. Textbook of Advanced Cardiac Life Support.

Dallas, Tex:American Heart Association; 1994: Chap 2: 2-2.
Anesthesia and Perioperative Care of the Combat Casualty

62

PLACEMENT OF AIRWAY DEVICES

An appropriate strategy for airway management

seeks to accomplish the goals previously described:

relief from obstruction, protection from pulmonary

aspiration, and treatment of airway injury. The

identification of airway injuries in combat casualties requires that immediate attention be instituted

to the particular problem. Casualties who are victims of head injury or exposure to chemical agents

will need urgent airway control. Casualties with

thoracic injuries may need airway control simply to

control secretions. Selection of the appropriate

airway-management technique requires a knowledge of the injuries received, the availability of

airway equipment, and the degree of airway-management skill held by the medical personnel. The

goal is to improve the combat casualty’s overall

status by ensuring safe, effective airway management. It must be understood that there is never a

single technique that is most appropriate for a particular patient. Various specialists who will participate in the care of the casualty may have different

perceptions regarding the degree to which the injury will influence the problem of airway management. This impression, when combined with another provider’s training and experience with airway

management, may result in the selection of another

technique that is also appropriate for the patient.

Suffice it to say that if all providers involved in the

care of the battle casualty have a solid understanding of the pathophysiology of injury and select a

technique that is compatible with those considerations, then the airway-management plan will be

appropriate for that individual patient. Indications

for airway and ventilatory management in the postoperative patient are discussed in Chapter 25, Acute

Respiratory Failure and Ventilatory Management.

Once the initial airway evaluation has been completed and an adequate airway has been ensured, or

at least supported by oxygen therapy and possible

airway adjuncts, it is appropriate to complete the

assessment of the casualty. It is now possible to

consider any anatomical airway limitations and the

availability of airway-management equipment to

allow for the formulation of primary and alternative plans to formally secure the airway. Suction

should be available, and all equipment such as

laryngoscopes and endotracheal tubes should be

checked. The casualty’s level of consciousness will

dictate the selection of the technique and the urgency of placing the airway device. It is important

to recognize that patients who are alert, oriented to

their situation, and who do not demonstrate overt

respiratory distress may do well with close observation and supplemental oxygen for a period of

time. All too often, these individuals are further

traumatized by overly aggressive, hasty attempts to

instrument the airway.

Airway Classification

An airway classification system may predict difficult tracheal intubations. The Mallampati airway

classification assumes that when the base of the

tongue is disproportionately large, the muscular

mass of the tongue will encroach upon the larynx

and make the laryngoscopic exposure of the glottic

opening difficult24:

• Class I: Faucial pillars, soft palate, and

uvula are visible.

• Class II: Faucial pillars and uvula are visible, but the uvula is masked by the base

of the tongue.

• Class III: Only the soft palate is visible; a

difficult intubation is predicted.

• Class IV: The soft palate is not visible; a

difficult intubation is predicted.

To properly assess the patient according to

Mallampati’s scheme, the casualty must be able to

sit upright with the head in the neutral position,

open his mouth as wide as possible, and be able to

protrude his tongue. The upper airway is then

inspected and graded.24 Although this classification may not be suitable for all combat casualties

due to their inability to sit or perform the required

maneuvers, it should be employed on appropriate

patients as part of the airway assessment, as Class

III and Class IV airways are predicted to be difficult

to intubate using standard laryngoscopy (Figure 3-

4).25

Anesthetizing the Airway

The anatomical areas that will be trespassed during airway management include the nasopharynx,

oropharynx, hypopharynx, glottis, and the subglottic areas. The structure that divides the upper

and lower airways is the glottis. The upper airway

is mainly innervated by the glossopharyngeal (cranial nerve IX) and the superior laryngeal (a branch

of cranial nerve X) nerves. The glossopharyngeal

nerve supplies the posterior third of the tongue

and the oropharynx to its junction with the na-
Airway Management

63

sopharynx. Its distribution includes the pharyngeal surfaces of the soft palate, epiglottis, and the

fauces to the junction of the pharynx and esophagus. The superior laryngeal nerve supplies the

mucosa from the epiglottis to and including the

vocal cords and the motor branch to the cricothyroid

muscle. The recurrent laryngeal nerve (a branch of

cranial nerve X) supplies the mucosa below the

vocal cords and the remainder of the intrinsic

muscles of the larynx.

If awake intubation is deemed necessary in a

responsive casualty, the application of topical anesthesia to the upper airway and consideration for

judicious use of intravenous sedation should be

entertained to facilitate airway manipulation. The

sensory input for the nasal mucosa is supplied by

many named nerve branches that route through the

trigeminal (ie, Gasserian) ganglion. Passing a

nasotracheal tube can be facilitated by using a local

anesthetic agent combined with a topical vasoconstrictor to both anesthetize and shrink the nasal

mucosa. Although 4% cocaine can accomplish both

purposes, a solution of 1% lidocaine combined with

0.25% neosynephrine or 0.05% oxymetazoline is

just as efficacious. Viscous lidocaine or lidocaine,

cetacaine, and benzocaine sprays may be used to

topically anesthetize the awake patient. Time is

required for these agents to penetrate the mucosal

tissue to provide adequate anesthesia. Sedation can

be accomplished with the judicious use of intravenous benzodiazepines, narcotics, or sedative-hypnotic agents such as sodium thiopental, etomidate,

or propofol—in small boluses, if necessary—in

arousable patients.

Class I Class III Class IV Class II

Fig. 3-4. Upper-airway classification is based on visible oral anatomy when the mouth is fully open and the patient is

in the sitting position. Class I reveals the soft palate, fauces, uvula, and the anterior and posterior tonsillar pillars. Class

II reveals all of the above structures except for the tonsillar pillars. Class III demonstrates that all of the above

structures—except the uvula—are obscured. In a class IV airway, all of the pertinent oral structures are obscured by

the tongue. Both class III and class IV airways predict a difficult laryngoscopic intubation. Reprinted with permission

from Benumof JL. Management of the difficult airway. Anesthesiology. 1991;75:1091.

Specific Nerve Blocks

Glossopharyngeal and superior laryngeal nerve

blocks augment topical anesthesia applied to the

pharynx and upper portion of the larynx. The

glossopharyngeal nerve block is performed by injecting 1 to 2 mL of 1% lidocaine behind each tonsillar pillar. Special angled needles and kits are available to perform this block. Caution should be

exercised to avoid injecting local anesthetic into the

carotid artery: this mishap is associated with seizure activity due to the rapid transport of the anesthetic agent to the brain. The use of a laryngoscope

will supply illumination and help to displace the

tongue to the side. The superior laryngeal nerve is

anesthetized by identifying the superior cornu of

the hyoid bone and moving slightly caudally toward

the thyrohyoid membrane. The fascia is pierced and

2 to 3 mL of 1% lidocaine is injected bilaterally.

If needed, providing anesthesia to the lower larynx and trachea is best accomplished by the

transtracheal instillation of 3 to 4 mL of 4% lidocaine

through the cricothyroid membrane to block the

recurrent laryngeal branches of the vagus nerve. A

note of controversy concerns this maneuver. If we

accept the dictum that, by definition, all trauma

patients have a “full stomach,” then the combat

casualty with traumatic wounds is at risk for gastric

regurgitation and pulmonary aspiration. Opponents of this practice argue that blocking the recurrent laryngeal nerves removes the last defense the

patient has to self-protect against pulmonary aspiration. Proponents argue that the medical provider

performs the block to facilitate the process of secur-
Anesthesia and Perioperative Care of the Combat Casualty

64

b

c

a ing the airway. Regardless of the merits of the

argument, however, blocking the recurrent laryngeal nerves allows the anesthesia provider a more

rapid and controlled passage of an endotracheal

tube whether blindly, under direct vision, or with

fiberscope assistance, with less coughing, retching,

or vomiting by the casualty.

Nasotracheal Intubation

The awake patient without suspicion of neck

injury may tolerate blind nasal endotracheal

intubation better than an oral endotracheal tube

placed with the use of a laryngoscope. Nasal

intubation requires less manipulation of the cervical spine than oral intubation and is not hampered

by jaw closing or biting. Slight flexion maneuvers

of the neck frequently facilitate blind nasal placement during spontaneous ventilation. The anesthesia provider advances the tube while listening at its

end to inspiratory breath sounds. A decrease in

sound occurs if the tube passes posterior to the

glottic opening. Repositioning and possibly rotating the tube while advancing it toward the open

glottis during inspiration is usually successful.

Correct placement within the glottis will be associated with an increase in breath sounds heard at the

end of the tube, and exhaled vapor that condenses

within the tube lumen may be visible during ventilation. Alternatively, the endotracheal tube may be

placed nasally and then directly guided into the

trachea under laryngoscopic visualization. The tube

tip may have to be manipulated into the trachea

with Magill forceps. It is important to avoid touching

the endotracheal cuff with the Magill forceps, as a tear

in the cuff will require that a new endotracheal tube be

placed. Nasotracheal intubation is contraindicated in

all casualties with midfacial injuries, basilar skull

fractures, disorders of hemostasis, foreign bodies in

the airway, or airway tumors.

Orotracheal Intubation

Oral intubation is the technique of choice in those

casualties who have a contraindication to the nasal

route, are obtunded with inadequate ventilation, or

are recognized to need the rapid establishment of a

secure airway. The goal of laryngoscopy is to align

the oral, pharyngeal, and laryngeal axes in such a

manner that the glottic opening can be visualized so

that an endotracheal tube can be introduced into the

trachea (Figure 3-5). The most commonly used

blades for laryngoscopy are the straight Miller type

and the curved Macintosh type, which are available

Fig. 3-5. Alignment of the oral–pharyngeal–laryngeal

axis to allow for laryngoscopy and endotracheal

intubation. (a) The long axes of the oral cavity, pharynx,

and larynx are not normally aligned when a person is in

the supine position. (b) Displacing the slightly flexed

head forward in relation to the neck aligns the pharyngeal and laryngeal axes. (c) Extension of the forwarddisplaced head will align the oral cavity with the conjoint

pharyngeal–laryngeal axis. The blade of the laryngoscope

displaces the epiglottis, exposing the glottis. Reprinted

with permission from Gaiser R. Airway evaluation and

management. In: Davison JK, Eckhardt WF III, Perese DA,

eds. Clinical Anesthesia Procedures of the Massachusetts General Hospital. 4th ed. Boston, Mass: Little, Brown; 1993: 177.

in various sizes (Figure 3-6).26 In an obtunded

patient, an oral endotracheal intubation can frequently be performed without the use of local anesthetic or supplemental sedative agents.

Since traumatized and obtunded casualties are at

risk for pulmonary aspiration, cricoid pressure

should be utilized if possible during endotracheal
Airway Management

65

a b c

Fig. 3-6. (a) The correct placement of the curved blade tip into the vallecula and the use of forward traction allows the

epiglottis to be displaced anteriorly to expose the glottic opening. (b) The tip of the straight blade is used to lift up the

epiglottis to expose the glottic opening. (c) The glottic structures visualized during laryngoscopy. Reprinted with

permission from Cummins RO. Textbook of Advanced Cardiac Life Support. Dallas, Tex: American Heart Association;

1994: 2-4, 2-5.

intubation (Figure 3-7). Firm compression of the

cricoid cartilage (not the thyroid cartilage) by an

assistant is effective in occluding the esophageal

lumen and preventing passive gastric regurgitation

into the larynx.27 To avoid esophageal injury, cricoid pressure should be released if the patient

retches. The application of cricoid pressure should

not displace the cervical spine from the neutral

position (the assistant can support the dorsal cervical spine with the other hand).

Cricoid pressure may also facilitate endotracheal

intubation by also stabilizing the larynx, thereby

helping to guide the tube tip into the glottic opening. The assistant should feel the tube pass through

the larynx. Cricoid pressure may be relatively difficult to apply if the casualty is wearing a rigid

cervical collar. If the collar can be removed and the

cervical spine stabilized in the neutral position during the intubation procedure, the benefits of avoiding pulmonary aspiration will far outweigh the

danger of injury to the cervical spinal cord. In many

instances, a nasogastric tube will have been placed

before the casualty receives endotracheal intubation.

The placement of a nasogastric tube relieves increased intragastric pressure and may allow for

removal of a portion of the gastric contents. With a

nasogastric tube in place, cricoid pressure can be

adequately applied without increasing the risk of

regurgitation or aspiration.28 Cricoid pressure

should be maintained until successful endotracheal

intubation is properly verified.

To complete endotracheal intubation, oxygenation, ventilation if necessary, and oral suctioning

are required prior to both induction of general anesthesia and the performance of direct laryngoscopy.

Attention to detail regarding laryngoscope and blade

selection, patient positioning, and intubating technique is essential, as emergent intubating conditions may be less than optimal. Developing good

intubating techniques and adhering to them in these

situations are mandatory to provide skillful airway

management.

Fig. 3-7. The cricoid cartilage should be firmly compressed with 44 N (10 lb or 4.5 kg) pressure to occlude the

esophagus and continue to be held until successful

intubation has been verified. Reprinted with permission

from Horswell JL, Cobb ML, Owens MD. Anesthetic

management of the trauma victim. In: Zuidema GD,

Rutherford RB, Ballinger WF, eds. The Management of

Trauma. 4th ed. Philadelphia, Pa: WB Saunders; 1985: 133.

Firm downward pressure by assistant

occluding esophagus with the cricoid

cartilage (Do not press on thyroid cartilage

or trachea)
Anesthesia and Perioperative Care of the Combat Casualty

66

Rapid-Sequence Induction of Anesthesia

The casualty with a traumatic wound may have

neither an airway injury nor difficulty with ventilation yet may require surgical intervention to treat

his injury. Again, all casualties are considered to

have full stomachs, which puts them at risk for

pulmonary aspiration. It is important to realize that

it is the time of injury, not the time of last ingestion,

that is the most significant. If awake intubation

cannot be performed, then a rapid-sequence induction of general anesthesia with cricoid pressure and

endotracheal intubation should be performed.

Prior to induction of general anesthesia, it is

important to provide an FIO2 of 1.0 for a few minutes

through a tight-fitting mask to denitrogenate the

lungs and to ensure maximum alveolar and arterial

oxygen saturation. If it is impractical to fully

denitrogenate prior to induction, an attempt should

be made to maximize oxygen saturation by having

the casualty take four deep breaths of pure oxygen

prior to induction of anesthesia.

The rapid-sequence induction of anesthesia is a

technique of quickly administering a sedative-hypnotic agent in conjunction with a muscle relaxant to

cause rapid unconsciousness and tracheal muscle

relaxation so that the trachea can be intubated as

quickly as possible. It is desirable to accomplish

this task within less than 90 seconds if possible. No

attempt should be made to ventilate the patient by

mask after induction of anesthesia until correct

placement of the endotracheal tube has been confirmed. The intravenous induction of general anesthesia can be accomplished with ketamine,

etomidate, propofol, or sodium thiopental.

Thiopental is the most well-known drug for contributing to myocardial depression and hypotension,

but all of the induction agents can be associated

with these conditions.29,30

To allow for endotracheal intubation, succinylcholine, a depolarizing muscle relaxant agent, remains the most reliable agent for producing rapid

relaxation of the airway musculature. It has a short

duration of action due to its chemical breakdown by

plasma cholinesterase. Newer nondepolarizing

agents of the aminosteroid and benzylisoquinoline

classes that are administered in large doses have

been shown to be acceptable alternatives for rapid

tracheal intubation.31–34 The disadvantage to their use

is related to their long duration of action following

large doses. The nondepolarizing agents generally

require that their action be reversed with a cholinesterase-inhibiting agent such as neostigmine combined

with an antimuscarinic agent such as atropine. See

Chapter 11, Neuromuscular Blocking Agents, for a

more complete discussion of this subject.

or surgery, paralysis of the vocal cords is occasionally related to endotracheal intubation, especially if

the patient is intubated for a prolonged time.37 This

injury is typically unilateral, presents clinically with

a complaint of hoarseness, does not cause respiratory obstruction, and resolves with time.

Complications associated with prolonged

intubation include pressure necrosis of the nasal

alae, lips, and tongue. In a patient with a nasal

endotracheal tube in place, unrecognized purulent

sinusitis may progress to meningitis or sepsis. Vocal cord granuloma, tracheal ulceration, and

subglottic stenosis are known complications of

prolonged intubation. Although these complications may be unavoidable, attention to technique

and early recognition of complications with appropriate consultation may minimize associated

morbidity.

Although a given injury may not directly involve

the airway, it may be worsened by delayed, improper, or inadequate airway management. Combat casualties frequently have multiple sites of inCasualties with respiratory compromise, in whom

an effective airway is not promptly established, can

die or suffer irreversible neurological injury. Other

complications can be divided into (a) an acute group,

which includes mechanical trauma to the airway or

the sequelae of pulmonary aspiration, and (b ) a

chronic group, which comprises the complications

associated with prolonged intubation and mechanical ventilation (Exhibit 3-2). The latter complications are addressed in Chapter 25, Acute Respiratory Failure and Ventilatory Management, and are

not discussed further in this chapter.

Traumatic complications include injuries to the

nasal septum, dental or labial structures, mucosal

tissue disruption, and hemorrhage.35 Mucosal dissection that is complicated by infection may progress

to sinusitis, retropharyngeal abscess formation with

possible spread to the mediastinal space, and generalized life-threatening sepsis. Vigorous intubation

attempts may disrupt or dislocate arytenoid or other

laryngeal cartilages.36 Although damage to the innervation of the larynx is typically a result of trauma

COMPLICATIONS OF AIRWAY MANAGEMENT
Airway Management

67

Oral Intubation

Trauma from laryngoscopy

Excessive cervical spine motion

Esophageal intubation

Pneumothorax

Damage to endotracheal tube

Vomiting or aspiration or both

Broken teeth

Inadvertent extubation

Laryngeal trauma

Right main bronchus intubation

Mouth debris forced down the trachea

Esophageal perforation

Laryngotracheal disruption

Blood clots obstructing the tube

Nasal Intubation

All complications listed above plus:

False passage in posterior pharynx

Air entry from paranasal sinuses into

subcutaneous tissues

Nosebleed

Prolonged intubation:

Sinusitis

Necrosis of the nose

EXHIBIT 3-2

COMPLICATIONS OF INTUBATIONS

IN TRAUMA PATIENTS

Reprinted with permission from Stene JK, Grande CM,

Barton CR. Airway management for the trauma patient.

In: Stene JK, Grande CM, eds. Trauma Anesthesia. Baltimore, Md: Williams & Wilkins; 1991: 80.

jury, which must be prioritized for seriousness of

injury and which may require selection of techniques that place one organ system at risk while

minimizing damage to another. There are no rigid

formulas for selecting a technique for these patients, as each casualty must have an airway-management plan based on individual assessment of

the injury and its associated physiological impact.

This information, combined with knowledge of the

provider skills and the available airway equipment,

is used to formulate a prompt, effective approach to

airway management.

Regurgitation and Aspiration

All trauma victims and combat casualties are

assumed to have gastric atony beginning at the time

of their injury and therefore are at risk for gastric

regurgitation and pulmonary aspiration due to their

having a full stomach. The risk is not minimal, as

WDMET autopsy data from soldiers killed on the

battlefield confirm that regurgitation and aspiration are common agonal events.3 Although most

endotracheal intubations will be performed by

trained anesthesia personnel, an appreciation of the

problem must be entertained by all medical personnel who come in contact with the battle casualty.

Manual maneuvers such as the use of cricoid

pressure during endotracheal intubation will help

to minimize the risk of passive regurgitation and

aspiration. A nasogastric tube may help to partially

decompress gastric volume and air. If time allows,

the intravenous pharmacological manipulation of

gastric volume and pH can help to reduce the risk of

aspiration. Histamine-2 receptor blocking agents

given intravenously (eg, cimetidine 300 mg,

ranitidine 50 mg) help both to decrease the rate and

volume of acid secretion and to increase the pH of

gastric contents.38–40 Unfortunately, pharmacological treatment for aspiration prophylaxis requires

time for the agents to work and may not be helpful

in emergency airway-management situations.

Metoclopramide 10 mg, administered intravenously,

promotes gastric emptying into the small intestine

within a few minutes by relaxing the pylorus and

increasing peristaltic activity.41 When time precludes the use of intravenous agents for aspiration

prophylaxis, a nonparticulate antacid such as sodium citrate 30 mL, or sodium bicarbonate 8.4% 2.5

to 5.0 mL, administered orally or through a

nasogastric tube, will raise the gastric pH for up to

30 minutes.42 The benefit from the increased gastric

pH outweighs any concern over increased volume

of stomach contents; in addition, the stomach contents may be less harmful even if aspirated into the

airway. Although the acid-buffering power of colloidal antacids is superior to that of nonparticulate

solutions, the particulate antacids have been shown

to worsen the pneumonitis associated with pulmonary aspiration.43

Management of Pulmonary Aspiration

If gastric regurgitation and pulmonary aspiration have occurred, then the oropharynx and trachea should be suctioned immediately, and the pH
Anesthesia and Perioperative Care of the Combat Casualty

68

of the secretions should be determined. The casualty should be intubated if this has not already been

accomplished. Bronchoscopy may be indicated if

the aspiration of particulate matter has occurred.

Casualties with significant aspiration may present

with immediate bronchospasm, wheezing on auscultation, and elevated peak airway pressures. A

high FIO2 along with PEEP should be delivered.

Serial arterial blood gas measurements will reflect

the degree and course of the pulmonary injury. The

patient should be observed in an intensive care

setting and given supportive therapy. Chest radiography is useful in following the clinical course,

but radiographic changes lag behind the clinical

course by several hours. Antibiotic therapy is indicated only for proven bacterial infection. Steroids

are not indicated for the management of this condition. Pulmonary aspiration progressing to the adult

respiratory distress syndrome (ARDS) is associated

with mortality as high as 50%.44

A guidewire (0.030 in.) or an epidural catheter can

be placed through the cricothyroid membrane in a

retrograde fashion to pass through the oropharynx

or nasopharynx. The guidewire or the catheter can

then be retrieved, and an endotracheal tube may

then be guided over the device into the laryngeal

inlet. The wire or catheter can then be removed and

the endotracheal tube advanced into the trachea.50

Alternatively, at higher echelons of care, if a

fiberscope is available, it can be preloaded with an

endotracheal tube and then advanced over the retrograde wire and visually directed into the trachea.

The wire is then withdrawn and the endotracheal

tube is advanced under fiberscope guidance.

Other alternative methods for intubation are

available, but these require specialized equipment

that may not be available at forward areas of care.

These devices, including the laryngeal mask airway

(LMA), lightwand, and fiberoptic laryngoscope, all

of which may facilitate the management of the difficult or failed intubation, are presently not included in the Department of Defense’s Deployable

Medical Systems (DEPMEDS) equipment list, although they are available in most fixed hospitals.

The LMA (a new device that is under consideration for the DEPMEDS equipment list) bridges the

gap in airway management between a face mask and

endotracheal intubation.45,51 The LMA is designed to

be placed blindly into the pharynx, forms a lowpressure seal around the laryngeal inlet, and allows

for either spontaneous or low (≤ 20 cm H2O) positive-pressure ventilation. This device is available in

various sizes, is relatively easy to insert, and has a

role in the management of the difficult or failed

intubation in a casualty who does not have trauma

to the airway (Figures 3-10 through 3-17). The LMA

is not suitable for an awake patient, as it causes as

much gagging as an oropharyngeal airway. It is

possible to pass a small endotracheal tube through

the larger LMAs, either using a fiberscope or blindly

through the LMA grate that sits above the glottis.

MANAGEMENT OF THE FAILED INTUBATION

In the general population who present for surgery without evidence of injury to the airway, tracheal intubation or the maintenance of a patent

airway will be difficult in an estimated 1% to 3% of

patients.45 The inability to secure a patent airway in

a patient who cannot be ventilated is perhaps one of

the most serious situations faced in airway management. Consequently, it is imperative that alternative nonsurgical and surgical strategies be considered. Repeated attempts at intubation using the

same techniques seldom succeed and increase the

potential for iatrogenic airway injury. An algorithmic approach to the difficult airway and failed

intubation has been promulgated to help formulate

alternative strategies in the management of this

problem (Figure 3-8).25 The key to success is the

combination of carefully assessing the airway, formulating and proceeding with a plan that does not

limit other options, and having assistance and extra

equipment to manage this demanding problem.

The decision to place a surgical airway should be

considered early if advanced airway equipment or

individuals skilled in advanced airway-management techniques are not available.

In the first and second echelons of care,

cricothyroidotomy is the accepted approach to securing an emergency surgical airway when it is

impossible to ventilate a casualty by nonsurgical

means (Figure 3-9). The decision to perform either

cricothyroidotomy or tracheostomy at the third or

fourth echelons of care will depend on both the

availability of surgical personnel trained in

tracheostomy and the urgency of airway access.

The cricothyroid membrane can be used to gain

access to the airway using large-bore catheters,

wires, or percutaneous airway devices. If largebore (12- or 14-gauge) catheters are used, temporary oxygenation and ventilation using a bag-valvemask or jet-ventilation equipment attached to a

high pressure oxygen source can be used. Percutaneous airway devices can be used, if available.46–49
Airway Management

69

Fig. 3-9. Performance of cricothyroidotomy with a scalpel. Reprinted with permission from Cummins RO. Textbook of Advanced Cardiac Life Support. Dallas, Tex: American Heart Association; 1994: Chap 2: 2-13.

Fig. 3-8. An algorithmic approach to the difficult airway

and failed intubation. Reprinted with permission from

Benumof JL. Management of the difficult adult airway.

Anesthesiology. 1991;75:1090.
Anesthesia and Perioperative Care of the Combat Casualty

70

Fig. 3-10. The cuff of the laryngeal mask airway should be

tightly deflated to ensure that there are no folds near the

tip of the mask. Reprinted with permission from Baskett

PJF, Brain AIJ. The Use of the LMA in Cardiopulmonary

Resuscitation Handbook. 1st ed. Henley-on-Thames, England: Intavent Research Ltd; 1994: 5.

Fig. 3-11. Lubrication should be applied only to the rear

of the laryngeal mask airway, not to the open bowl of the

mask. Reprinted with permission from Baskett PJF, Brain

AIJ. The Use of the LMA in Cardiopulmonary Resuscitation

Handbook. 1st ed. Henley-on-Thames, England: Intavent

Research Ltd; 1994: 5.

Fig. 3-12. Under direct vision, press the mask tip upward

against the inner surface of the patient’s upper incisors to

flatten the tip. Arrows indicate direction of applied pressure exerted by each hand. Reprinted with permission

from Baskett PJF, Brain AIJ. The Use of the LMA in Cardiopulmonary Resuscitation Handbook. 1st ed. Henley-onThames, England: Intavent Research Ltd; 1994: 7.

Fig. 3-13. Using the index finger, keep pressing the mask

upward as it is advanced into the pharynx, to ensure that

the tip of the mask remains flattened and avoids engaging the patient’s tongue. Reprinted with permission from

Baskett PJF, Brain AIJ. The Use of the LMA in Cardiopulmonary Resuscitation Handbook. 1st ed. Henley-onThames, England: Intavent Research Ltd; 1994: 8.
Airway Management

71

Fig. 3-16. While grasping the tube and continuing to exert

downward pressure, remove the index finger from the

patient’s oral cavity. Reprinted with permission from

Baskett PJF, Brain AIJ. The Use of the LMA in Cardiopulmonary Resuscitation Handbook. 1st ed. Henley-on-Thames,

England: Intavent Research Ltd; 1994: 9.

Fig. 3-14. With the patient’s neck flexed and head extended, press the mask into the posterior pharyngeal

wall using the index finger. The index finger must be

directly in line with the mask aperture. Reprinted with

permission from Baskett PJF, Brain AIJ. The Use of the LMA

in Cardiopulmonary Resuscitation Handbook. 1st ed. Henleyon-Thames, England: Intavent Research Ltd; 1994: 8.

Fig. 3-15. The mask can be seated into position with

one fluid motion while the anesthesiologist continues to

push the mask with the index finger. Reprinted with

permission from Baskett PJF, Brain AIJ. The Use of the

LMA in Cardiopulmonary Resuscitation Handbook. 1st

ed. Henley-on-Thames, England: Intavent Research Ltd;

1994: 9.

Fig. 3-17. Inflate the mask with the recommended amount

of air. The mask should rise slightly as it seats itself in the

correct position over the larynx. A slight airleak (< 20 cm

H2O) is acceptable if the chest moves with respiration.

Deflate and reseat the mask if there is a large airleak (> 20

cm H2O). Reprinted with permission from Baskett PJF,

Brain AIJ. The Use of the LMA in Cardiopulmonary Resuscitation Handbook. 1st ed. Henley-on-Thames, England:

Intavent Research Ltd; 1994: 9.
Anesthesia and Perioperative Care of the Combat Casualty

72

The lightwand is a lighted, flexible stylet over

which an anesthesia provider can blindly place an

endotracheal tube into the trachea through either

the mouth or the nose (Figure 3-18). The lightwand

can be positioned easily without manipulating the

neck. The instrument should be used in dim ambient light and advanced following the curve of the

tongue. A glow seen over the lateral neck indicates

that the tip lies in the pyriform fossa. A loss of tip

brightness generally indicates that the lightwand

has entered the esophagus. A marked glow in the

anterior neck with a cone of light pointing caudad

indicates its proper position at the glottic opening,

and the tube can then be slid off the stylet and

passed into the trachea.52,53

The fiberoptic laryngoscope is a shortened version of the fiberoptic bronchoscope. It requires a

light source and incorporates a suction port (which

can also be used to entrain oxygen) and optics into

a flexible bundle that fits easily through an endotracheal tube. It allows for direct visualization of the

airway structures. These fiberscope devices are

expensive, somewhat fragile, and require that anesthesia providers be trained to use them. The devices are likely to be available in only the higher

echelons of care. The Patil-Syracuse mask (manufactured by Bay Medical, Clearwater, Fla.) is a face

mask modified with an entry port for the introduction of a fiberscope during mask ventilation. SpeFig. 3-18. Once the cone of light is seen at the glottic

opening, the endotracheal tube is passed from the lighted

stylet into the trachea. Photograph: Courtesy of Laerdal

California, Inc, Long Beach, Calif.

cialized oral airways such as the Williams (manufactured by Bay Medical, Clearwater, Fla.), Berman

(manufactured by Sun Medical, Clearwater, Fla.),

and Ovassapian (manufactured by Bay Medical,

Clearwater, Fla.) intubating airways have been developed to facilitate introduction of the fiberscope

tip into the laryngeal orifice.54–57

SPECIAL AIRWAY-MANAGEMENT CONSIDERATIONS

Head Injury

In the civilian setting, where motor-vehicle blunt

trauma predominates as the cause for injury,

a head injury occurs every 15 seconds, and a patient

dies of a head injury every 12 minutes, a physician

dealing with trauma is confronted with a headinjured patient almost every day. Approximately

50% of all trauma deaths are associated with head

injury, and more than 60% of vehicular trauma

deaths are due to head injury.58(p161)

Both early recognition of intracranial injury and

institution of appropriate therapy will minimize

secondary neuronal injury and increase the potential for neurological recovery. Airway management

for the casualty with head injuries has three goals. The

first is to provide adequate ventilation to those whose

medullary respiratory centers may have been compromised due to increased intracranial pressure

(ICP) from edema or hemorrhage. The second is to

reduce the risk for gastric regurgitation and pulmonary aspiration, because a decreased sensorium with

possible compromise to cranial nerve function alters the normal protective airway reflexes. The

third is to decrease the risk for aspiration and allow

for the transient use of hypocapnia (PaCO2 25–30

mm Hg) to prevent or manage increased ICP.59

An obtunded state, a deterioration in mental

status, or a Glasgow coma scale determination of 8

points or less signals the need for immediate airway

management (Exhibit 3-3).60,61 Ideally, endotracheal

intubation should be accomplished rapidly and

under deep anesthesia so that the untoward hemodynamic effects of laryngoscopy can be blunted.

Hypertension in response to laryngoscopy and endotracheal tube placement may exceed the limits of

cerebral autoregulation and contribute to further

intracranial hemorrhage, edema, and an increase in

ICP with compromise of cerebral perfusion pressure (CPP) and cerebral function. Coughing or

bucking in response to intubation efforts elevates

not only cerebral-inflow pressure but also central

venous pressure, with resultant decreases in CPP.
Airway Management

73

EXHIBIT 3-3

GLASGOW COMA SCALE

Eye Opening

Spontaneous _____ 4

To verbal command _____ 3

To pain _____ 2

None _____ 1

Verbal Response

Oriented and converses _____ 5

Confused and converses _____ 4

Inappropriate words _____ 3

Incomprehensible words _____ 2

None _____ 1

Motor Response

Obeys command _____ 6

Localizes pain with a purposeful

response _____ 5

Flexion withdrawal _____ 4

Abnormal flexion _____ 3

Decerebrate extension _____ 2

None _____ 1

While hypertension is poorly tolerated in casualties

with brain injuries whose blood–brain barrier is

disrupted, hypotension is just as dangerous: inadequate cerebral perfusion may occur in areas of

brain injury where cerebral autoregulation of blood

flow is compromised or nonexistent.

If a barbiturate such as thiopental is available, its

use as an induction agent in the dose range of 3 to 5

mg/kg will provide deep anesthesia, decrease the

cerebral metabolic rate of oxygen demand (CMRO2),

and not interfere with any cerebral autoregulation

that remains intact.62 Barbiturates can depress cardiovascular function and their use may be limited

in a casualty who is hypovolemic and hypotensive.

Etomidate 0.1 to 0.3 mg/kg or propofol 1 to 2 mg/

kg may be acceptable alternatives. Ketamine should

be avoided in the casualty with head injuries.

Lidocaine 1.5 to 2.0 mg/kg will blunt the tracheal

response to laryngoscopy, augment anesthetic

depth, and serve as a cerebral vasoconstrictor.63

The use of muscle relaxants can provide stable

intubating conditions, prevent coughing with resultant elevation of ICP, and minimize the risk for

gastric regurgitation and pulmonary aspiration.

Succinylcholine has been the muscle relaxant of

choice due to its reliable rapid onset and short

duration of action, but it has the potential to cause

muscle fasciculation–induced increases in ICP, although this issue is controversial.64–66

Cervical Spine Injury

Cervical spine injuries with cord compromise at

or above the C-3 level mandate immediate airway

control and mechanical ventilation. Casualties with

cervical injuries may also require intubation due to

other areas of trauma.67 If ventilation is adequate,

any conscious casualty presenting with neck pain

or neurological deficit, or one who is unconscious,

will need radiographic examination of the cervical

spine to include visualization of C-7 before cervical-fixation devices are removed or the airway is

instrumented. If immediate intubation is required

prior to radiographic examination, or if bony or

ligamentous cervical instability is diagnosed, then

cervical stabilization should be accomplished by

the senior surgeon while the most skilled endoscopist manages the airway. If not otherwise indiA normal individual would score 15, while a patient in

profound coma would score 3. A score of 8 or less is considered indicative of a severe head injury, and endotracheal

intubation should be performed to protect the airway.

Painful stimuli should be administered by pressure over the

supraorbital notch, or by pressure on a nail bed with a

pencil. The best performance score at each time of testing

should be reported. Some centers record a score before and

after resuscitation has been completed.

Cold caloric testing and tonic neck reflexes provide information regarding the integrity of the brainstem in comatose

patients.
Anesthesia and Perioperative Care of the Combat Casualty

74

cated, a blind nasal intubation may be accomplished

with minimal manipulation of the airway. The

application of topical anesthesia may help to minimize coughing or gagging. Direct laryngoscopy

can be accomplished with cervical stabilization to

avoid flexion, and particularly extension, of the

cervical spine. The use of anesthetic agents in any

casualty with a high cervical cord injury should be

approached with caution, as the casualty may have

an altered sympathetic nervous system response to

these agents.68

Eye Injury

Penetrating (ie, open) ocular injuries are commonly seen in combat casualties who have received

multiple fragment wounds. The care of casualties

with open globe injuries should minimize any

coughing or straining to prevent extrusion of intraocular contents.16 The potential for ocular salvage and preservation of visual function must be

assumed until a complete examination can be performed by an ophthalmic surgeon. Airway management will require deep anesthesia with muscle

relaxation to avoid further loss of intraocular contents. Succinylcholine has been considered to be

relatively contraindicated in open eye injuries because muscle fasciculations have the potential to

increase intraocular pressure. Pretreatment with a

small dose of a nondepolarizing muscle relaxant

has been shown to minimize but not ablate this

problem,69 although one large study70 has indicated

that the increased intraocular pressure seen with

the use of succinylcholine is more a theoretical than

a clinical concern.69 Higher-than-usual intubating

doses of nondepolarizing muscle relaxant agents

are acceptable alternatives to succinylcholine in

appropriate patients.31–34

DIRECT INJURY TO THE AIRWAY

Maxillofacial Injury

The combat casualty suffering from multiple traumatic injuries, especially head injures, frequently

has associated midfacial and mandibular abnormalities. Medical personnel should determine the

presence of these injuries before instrumenting the

airway. Casualties with facial lacerations often

present with copious bleeding that may contribute

to airway obstruction. Relief of obstruction can

frequently be obtained with gentle suctioning and,

if possible, by allowing the casualty to sit forward

rather than lie supine. Gentle, forward traction on

an unstable, fractured mandible may also relieve

simple obstruction. The nasal approach to endotracheal intubation is contraindicated in the casualty

with midfacial fractures. Passage of endotracheal,

gastric, or suction tubes via the nares may dislodge

bone fragments or introduce infection, or the tube

may pass upward into the cranial vault if the cribriform plate has been disrupted.

If endotracheal intubation is required, direct visualization of the larynx is usually possible and can

often be performed in an awake patient after the

topical application of anesthetic agents to the airway. Fiberoptic intubation can be considered, but

secretions and bleeding often obscure the view and

make this technique very difficult. A blind oral

technique such as using a lightwand may be helpful

if direct visualization is difficult. If anesthesia of the

larynx and trachea is needed, previously discussed

approaches to the airway and aspiration-prevention

techniques can be utilized.

It is important to make an early determination if

airway instrumentation above the larynx would be

very difficult or futile. If this is true, or if multiple

intubation approaches fail, then arrangements need

to be made for an urgent or emergent surgical

approach to the airway.

Laryngeal and Tracheal Injury

Direct trauma to the larynx and trachea is relatively rare, based in part on the anatomical relationship of these to bony structures: the mandible provides a bony shelf that overhangs the larynx and

hyoid bone, while the sternum offers protection to

the trachea. Injuries to the larynx and trachea can be

divided into (a) blunt and (b) penetrating types.

Airway compromise results either from disruption of laryngotracheal structures or from secondary compression due to hemorrhage or subcutaneous emphysema. Blunt trauma to the anterior neck

may cause dislocation or fracture of the thyroid,

cricoid, or tracheal cartilages. Alternatively, a blow

to the chest may cause a concussive injury to the

trachea.71–73

Penetrating injuries may also damage the superior or recurrent laryngeal nerves, resulting in partial anesthesia and airway obstruction. A neck

wound that causes a divided cervical trachea is best

managed by directly intubating the distal portion of
Airway Management

75

the tracheal opening with a tracheostomy or endotracheal tube.

The diagnosis of tracheal injury is based on the

history of trauma to the area and finding the signs

and symptoms of airway obstruction. Stridor may

be the only presenting sign, although some victims

may have difficulty with phonation. The inability

to vocalize the “E” sound may indicate arytenoid

dislocation or injury to the recurrent laryngeal nerve

with arytenoid weakness or paralysis. Airway obstruction tends to worsen with deep inspiration and

coughing. The proper recognition and care of these

patients requires that the examiner have a high

index of suspicion for airway injury.

Management of the casualty with a potential airway injury should be predicated on the knowledge

that such injuries have the potential to be rapidly

fatal. The casualty with obvious signs of obstruction such as hoarseness and dyspnea, especially in

the presence of subcutaneous air or a pneumothorax, requires immediate airway control. When

the larynx has been separated from the trachea or if

the trachea is disrupted, orotracheal intubation—

although sometimes possible—can be dangerous.

A tracheostomy using local anesthesia is the safest

approach in such a casualty. Once the airway is

secured, laryngoscopy and bronchoscopy are used

to establish the diagnosis. Intubation over a flexible bronchoscope is useful in preparation for operative repair during thoracotomy.

In addition to direct injuries to the airway, the

aspiration of foreign bodies can be life threatening.

Removal of foreign bodies requires the coordination and planning of anesthesia, surgical, and operating room personnel. The circumstances, location,

and description of the foreign body can be obtained

from history and physical examination, respiratory

symptoms, and radiographic studies. The anesthetic plan should allow for removal of the foreign

body without worsening the casualty’s respiratory

status.

The casualty who has airway obstruction from an

expanding infectious site or from aspiration of a

foreign body may require an anesthetic approach

that deviates from the usual rapid-sequence induction technique. These conditions often require that

a mask-inhalational induction of anesthesia be performed to (a) preserve spontaneous ventilation and

(b) allow for intubation under deep inhalational

anesthesia. The risk of gastric regurgitation and

pulmonary aspiration in these casualties is less than

the risk of being unable to ventilate or intubate a

patient with an abnormal airway who has received

a neuromuscular blocking agent.

Thermal Injury

Injuries to the airway caused by changes in temperature may be purely thermal in nature, due to

chemical exposure, or a result of both mechanisms.

A history of the events surrounding the inhalational injury and physical evidence of facial burns,

charred nasal vibrissae, or carbonaceous sputum

may provide an indication for immediate airway

management. Although a diagnosis may be suspected, a conclusive diagnosis of airway injury cannot

be made without examination of the casualty’s upper and lower airways, usually by a surgeon skilled

in the management of thermal injuries. Airway

edema from the original injury and subsequent

airway embarrassment occurs insidiously. Subsequent fluid-resuscitation therapy in the burned casualty may worsen airway edema and cause respiratory

obstruction at any time. Therefore, a high index of

suspicion of both airway injury and the need for airway management is essential in all thermally injured casualties. During the first 12- to 24-hour period

after the burn, succinylcholine may be used to facilitate endotracheal intubation during airway management. After the first day, during the intensive-care

phase of treatment, succinylcholine should be avoided.

The burn victim’s muscles rapidly develop extrajunctional receptors that are associated with an

exaggerated release of potassium in response to the

administration of succinylcholine, which frequently

results in a hyperkalemia-induced cardiac arrest.74

SUMMARY

Most combat casualties who survive long enough

to be admitted to field hospitals for the treatment of

their injuries will require some form of airway management during the course of their treatment. Most

of these casualties will have been through triage on

arrival at the medical facility and will receive

semielective resuscitative or reconstructive surgery.

Their airway management will be provided by

trained anesthesia providers. In a few casualties

(< 5%–10% of the total), emergency, lifesaving airway management may need to be carried out by

medical personnel before the casualty reaches a

field hospital. Combat casualties who require immediate airway control are usually in extremis due
Anesthesia and Perioperative Care of the Combat Casualty

76

to exsanguination, severe head injury, or destructive

injuries to the face or neck. Standard techniques to

provide endotracheal intubation should be applied to

all casualties except for those with direct airway

trauma. Patients with direct airway injuries can be

best managed by creating a surgical airway. Other

patients may benefit from alternative means to secure an adequate airway with such devices as the

laryngeal mask airway or lightwand if standard

endotracheal intubation is difficult. Once hypoxia

has been averted or treated, gastric regurgitation

and pulmonary aspiration remain the greatest

threats to the combat casualty who requires airway

management. At the hospital level, rapid-sequence

induction of anesthesia combined with cricoid pressure to facilitate endotracheal intubation will minimize the risk of pulmonary aspiration. Casualties

with potential cervical spine injury due to blunt

head or neck trauma need to be approached with

special caution, as manipulation of the neck has the

potential to cause injury to the cervical spinal cord.

Finally, thermally injured patients must be evaluated

for airway injury, and appropriate airway management must be instituted as expeditiously as possible.

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14. Rehwald G. Organization and Tactics of the Medical Service. Berlin, German Democratic Republic: Military Press,

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35. Blanc VF, Tremblay NAG. The complications of tracheal intubation: A new classification with a review of the

literature. Anesth Analg. 1974;53:202.

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37. Ellis PDM, Pallister WK. Recurrent laryngeal nerve palsy and endotracheal intubation. J Laryngol Otol.

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38. Strain JD, Moore EE, Markovchick VJ, Van Duzer Moor S. Cimetidine for the prophylaxis of potential gastric acid

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volume in outpatients. Anesthesiology. 1986;65:180–185.

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1982;26(5):417–420.

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45. Pennant JH, White PF. The laryngeal mask airway: Its uses in anesthesiology. Anesthesiology. 1993;79:144–163.

46. Bjoraker J, Kumar NB, Brown ACD. Evaluation of an emergency cricothyrotomy instrument. Crit Care Med.

1987;5(2):157–160.

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light (lightwand) versus blind nasal approach. Anesthesiology. 1986;66:69–71.

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55. Conyers AB, Wallace DH, Muller DS. Use of fiberoptic bronchoscope for nasotracheal intubation. Can Anaesth

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58. American College of Surgeons Committee on Trauma. Head trauma. In: Advanced Trauma Life Support Program

for Physicians. Chicago, Ill: American College of Surgeons; 1993: Chap 6: 161.

59. Shapiro HM. Intracranial hypertension: Therapeutic and anesthetic considerations. Anesthesiology. 1975;43:445.

60. Teasdale G, Jennett B. Assessment of coma and impaired consciousness: A practical scale. Lancet. 1974;2:81–84.

61. Wiener SL, Barrett J. Trauma Management for Civilian and Military Physicians. Philadelphia, Pa: WB Saunders;

1986: 115.

62. Newfield P. Anesthetic considerations in patients with increased intracranial pressure. ASA Refresher Courses in

Anesthesiology. 1988;16:157.

63. Hamill J, Bedford R, Weaver D, Colohan A. Lidocaine before endotracheal intubation: Intravenous or intratracheal.

Anesthesiology. 1981;55:578.

64. Marsh ML, Dunlop BJ, Shapiro HM, et al. Succinylcholine—intracranial pressure effects in neurosurgical

patients. Anesth Analg. 1980;59:550–551.

65. Contrell JE, Hartung J, Giffin JP, et al. Intracranial and hemodynamic changes after succinylcholine administration in cats. Anesth Analg. 1983;62:1006–1009.

66. Minton M, Stirt J, Bedord R. Increased intracranial pressure from succinylcholine: Prevention by prior

nondepolarizing blockade. Anesthesiology. 1986;63:165.

67. Ciba Foundation. Acute cervical spine injuries. Ciba Fdn Symp. 1980;32:1.

68. Milne B, Jenkins MT. Anesthetic considerations in the multiply injured patient. In: Meyer M, ed. The Multiply

Injured Patient with Complex Fractures. Philadelphia, Pa: Lea & Febiger; 1984: Chap 10: 96–112.

69. Miller RD, Way WL, Hickey RF. Inhibition of succinylcholine-induced increased intraocular pressure by nondepolarizing muscle relaxants. Anesthesiology. 1968;29:123–126.

70. Libonati MM, Leahy JJ, Ellison N. The use of succinylcholine in open eye surgery. Anesthesiology. 1985;62:637–640.

71. Schaffer S, Anderson R, Carder H. Management of the upper airway in the injured patient. In: Meyer M, ed. The

Multiply Injured Patient with Complex Fractures. Philadelphia, Pa: Lea & Febiger; 1984: Chap 2: 9–17.

72. Bertz JE. Maxillofacial injuries. Ciba Clin Symp. 1981;33:14.

73. Lambert GE Jr, McMurry GT. Laryngotracheal trauma: Recognition and management. Journal of the American

College of Emergency Physicians. 1976;5:883–887.

74. Haponik EF, Munster AM, Wise RA, et al. Upper airway function in burn patients. Am Rev Respir Dis.

1984;129:251–257.
Hemorrhage, Shock, and Fluid Resuscitation

81

Chapter 4

HEMORRHAGE, SHOCK, AND FLUID

RESUSCITATION

FREDERICK W. BURGESS, PH.D, M.D.*; MICHAEL J. SBOROV, M.D.†; AND DEAN R. CALCAGNI, M.D.‡

INTRODUCTION

PHYSIOLOGICAL CONSEQUENCES OF HEMORRHAGE

Cardiovascular Response

Fluid Compartment Shifts

Extracellular Fluid Loss

Oxygen Transport

HYPOVOLEMIA

Venous Access

Intravenous Fluid-Delivery Systems

Blood-Salvage Techniques

Intraosseous Fluid Infusion

RESUSCITATION FLUID SELECTION

Crystalloid Solutions

Colloid Solutions

Hypertonic Solutions

SUPPLEMENTAL THERAPEUTIC MEASURES

Patient Position

Pneumatic Antishock Garment

Supplemental Oxygen

Therapeutic Hypothermia

Intraarterial Infusion

Vasopressors

Vasodilators

CONDITIONS PECULIAR TO RESUSCITATING COMBAT CASUALTIES

Hyperthermia and Dehydration

Hypothermia

Thermal Burns

Hemorrhagic Shock and Head Injury

The Chemically Contaminated Casualty

SUMMARY

*Formerly, Major, Medical Corps, U.S. Army Reserve; Director, Anesthesia Research, Madigan Army Medical Center, Tacoma, Washington

98431-5000; currently, Department of Anesthesia, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903

†Lieutenant Colonel, Medical Corps, U.S. Army Reserve; Chief, Anesthesia and Operative Services, Madigan Army Medical Center, Tacoma,

Washington 98431-5000

‡Lieutenant Colonel, Medical Corps, U.S. Army; Staff Officer, Combat Casualty Care, U.S. Army Medical Research and Materiel Command,

Fort Detrick, Frederick, Maryland 21702-5000
Anesthesia and Perioperative Care of the Combat Casualty

82

INTRODUCTION

Victims of combat-related trauma may present

with the classical manifestations of hemorrhagic

shock following rapid exsanguination from a major

vascular structure. Hemorrhagic shock is the most

common cause of death among combat casualties.

Early recognition, control of the hemorrhage source

by effective first aid, and rapid volume restoration

with intravenous fluids are the ideal preparation

for definitive surgical repair of the injury. Unfortunately, most combat casualties manifesting evidence

of hypovolemia may not be rapidly transported,

may not have an obvious bleeding source, may suffer

from sleep deprivation, may have occult injuries, and,

depending on the climatic conditions, may suffer

from hyperthermia, hypothermia, and dehydration.

An understanding of the combat environment, the

climate, infectious epidemics, and the time of injury

are all important factors contributing to the delineation of an appropriate diagnosis and treatment plan.

This chapter focuses on the recognition and initial

treatment of hypovolemic shock in the combat casualty, with an emphasis on associated medical

conditions that may accompany and confound the

diagnosis and treatment of hypovolemia.

The adverse effects of hemorrhage on young and

healthy soldiers are directly related to two primary

factors: (1) decreased intravascular volume and (2)

inadequate oxygen-carrying capacity. Reductions

in intravascular volume and the associated organ

hypoperfusion initiate a variety of autonomic and

neurohumoral homeostatic responses, which are

designed to maintain or restore the circulating

plasma volume and organ perfusion. The consequences of inadequate oxygen delivery are organ

dysfunction and possible death.

Cardiovascular Response

The response to rapid hemorrhage is complex

and time dependent. The sudden fall in venous

return to the heart results in an immediate decrease

in cardiac stroke volume. Because the aortic arch is

less distended by blood, intraluminal pressure will

fall. The immediate response to the fall in pressure

is a diffuse activation of the sympathetic nervous

system caused by reflexes that arise in the aortic

and carotid baroreceptors. An additional component of this adrenergic response is caused by the

release of catecholamines from the adrenal medulla. The initial physiological effects are (a) increased heart rate and myocardial contractility; (b)

increased systemic vascular resistance, which is

due primarily to vasoconstriction of arterioles in

the splanchnic viscera and skeletal muscle; and (c)

decreased vascular capacitance, which arises primarily from constriction of the smaller veins and

venules. These responses tend to preserve perfusion of the critically important central organs such

as the heart and brain at the expense of the more

peripherally situated splanchnic viscera and skeletal muscles.

Augmentation of the immediate vasoconstrictor

response to hemorrhage occurs within minutes, with

the activation of the renin-angiotensin system (Table

4-1). The formation of angiotensin II, an extremely

potent generalized vasoconstrictor, contributes to

the restoration of the arterial blood pressure and

stimulates sodium conservation via the release of

aldosterone. Sodium conservation, together with

water conservation mediated via antidiuretic hormone secretion, also tends to restore the missing

blood volume. The major mechanism that reestablishes an effective circulating blood volume in the

first hours following a major hemorrhage is

transcapillary transfer of plasma water from the

intracellular fluid space to the intravascular fluid

space. Although this process begins within minutes, it requires many hours for completion.

If the hemorrhage continues or if its magnitude

overwhelms these compensatory mechanisms, a

vicious cycle may begin, arising from the profoundly

ischemic splanchnic viscera and skeletal muscle

(Figure 4-1). Ultimately, systemic hemostasis fails

for the following reasons:

• the ability of ischemic cells to maintain a

normal transmembrane ionic gradient is

lost,

• precapillary sphincters in the ischemic vascular beds relax,

• intravascular fluid leaves the circulation

and collects in the ischemic tissues,

• lactic and inorganic acids as well as possible myocardial depressants enter the circulation, and

• oxygen-derived free radicals are generated—especially at the beginning of resuscitation when the ischemic beds are

PHYSIOLOGICAL CONSEQUENCES OF HEMORRHAGE
Hemorrhage, Shock, and Fluid Resuscitation

83

Washout of Myocardial Depressants 

 From Ischemic Tissue 

 Loss of Fluid Into  

Extravascular Space

Blood Volume

Cardiac Output

Coronary Perfusion

Acidosis and Hypoxia

Perfusion of Extremities 

 and Splanchnic Bed

Blood Pressure

 Mean Aortic Pressure < 40 mm Hg

(lower limits of coronary autoregulation)

Ischemia

 Relaxation of 

Precapillary Sphincters Cardiac Function

TABLE 4-1

COMPENSATORY RESPONSE TO

HEMORRHAGIC SHOCK

Response Times Systemic Response

Few seconds Sympathetic nervous system

Vasoconstriction

Tachycardia

Few minutes Renin-angiotensin system

Vasoconstriction (Angiotensin II)

Sodium conservation

Aldosterone secretion

Glucocorticoid secretion

Water conservation

Vasopressin secretion (ADH)

Several minutes Fluid compartment shifts

Transcapillary refill

Thirst

reperfused—and add to the cellular damage already caused by ischemia.

As the peripheral component of systemic hemostasis

fails, the centrally circulating blood volume falls,

leading to cardiac and respiratory dysfunction and

further reduction in cardiac output and blood pressure. Respiratory compensation for the increasing

metabolic acid load fails as the capacity of respiratory muscles is impaired by hypoperfusion. Acidosis, in conjunction with declining coronary perfusion pressure, impairs cardiac function; this leads

to a further fall in cardiac output and blood pressure. Even vigorous resuscitation instituted at this

time may not prevent death.

Fluid Compartment Shifts

After an untreated casualty sustains a major hemorrhage, restoration of the intravascular fluid compartment may require many hours as interstitial

fluid is drawn into the intravascular compartment

through alterations in the normal balance between

the transcapillary hydrostatic and oncotic pressures.

This phenomenon, transcapillary refill, depends on

both adequate interstitial fluid reserves and the

integrity of the capillary bed. In the average adult

male, total body water accounts for approximately

Fig. 4-1. Positive feedback loops (a departure from the

normal steady state, which induces an ever-increasing

departure) that may possibly develop and lead to death

following massive hemorrhage can involve either the

heart or the peripheral vascular beds of the soft tissues of

the extremities and the splanchnic organs. The loops are

not independent because the magnitude of cardiac output is a component of both. The central role of cardiac

output means that a decline in the heart’s pumping

action (if of sufficient duration and magnitude) can, by

reducing peripheral perfusion, adversely affect myocardial function. This causes a further decline in the heart’s

pumping action. The importance of myocardial depressants in hemorrhagic shock, in contrast to septic shock,

remains controversial. Adapted with permission from

Bellamy RF, Pedersen DC, DeGuzman LR. Organ blood

flow and the cause of death following massive hemorrhage. Circ Shock. 1984;14:115.

60% of total body weight.1 Two thirds of body water

is distributed within the intracellular compartment.

The remaining one third is located in the extracellular fluid compartment; 25% to 30% of this compartment comprises the intravascular plasma volume

(approximately 5% of the total body water), with

the remainder making up the interstitial fluid space.

Water freely distributes between each compartment

by passive diffusion; however, ionic equilibrium is

primarily determined by selective permeability, or

ion-selective active transport, or both, within each

compartment. Water, ions, and, to a variable extent,

proteins, are freely exchanged between the intravascular and much of the interstitial fluid compartments. The transmural exchange of fluid between

the intravascular compartment and the interstitium

can be described by Starling’s equation:
Anesthesia and Perioperative Care of the Combat Casualty

84

fluid flux = K[(Pc – Pi) – s (πc – πi)]

where K represents the capillary filtration coefficient; Pc and Pirepresent the hydrostatic pressure of

the intravascular (capillary) and interstitial compartments, respectively; s, which is known as the

reflection coefficient, represents the impermeability of the membrane to a given substance; and πc and

πi represent the oncotic pressure of the intravascular and interstitial fluid compartments, respectively.2

(See Chapter 25, Acute Respiratory Failure and

Ventilatory Management, for further discussion of

Starling’s equation.)

In hemorrhagic shock, constriction of the

precapillary sphincter should decrease the net flow

of fluid out of the intravascular space (decreased Pc)

and promote the return of interstitial fluid into the

intravascular compartment (transcapillary refill).

Conversely, the loss of precapillary sphincter tone

in late shock is an important factor leading to decompensation and death.

Extracellular Fluid Loss

Combat casualties presenting for care several

hours after being injured may suffer from (a) hemorrhage-induced intravascular volume depletion

and (b) preexisting depletion of the extracellular

fluid compartment that is caused by concomitant

dehydration secondary to environmental or nutritional factors. The importance of restoring the

interstitial fluid compartment, in addition to restoring the circulating blood volume, was demonstrated

in classic experiments performed during the 1950s.3

Using a dog hemorrhagic shock model, the researchers found improved survival among the animals

that were resuscitated with both lactated Ringer’s

solution and their shed blood, as opposed to resuscitation with shed blood alone or shed blood and

additional plasma. Because the crystalloid fluid is

distributed through the body water, it was soon

afterwards determined that restoration of the intravascular volume required the infusion of volumes

3- to 4-fold greater than the putative missing volume;

that is, after 1 L of lactated Ringer’s solution is infused,

only 250 mL will remain in the intravascular space.

Trauma and severe hemorrhage frequently lead

to a reduction in the functional extracellular fluid

compartment. The reduction in extracellular fluid

is partly attributable to hemorrhage; transcapillary

refill; and the sequestration of interstitial (isotonic)

fluid, which represents the third-space loss. Recommendations for replacing the third-space fluid

sequestration include administering (a) a balanced

salt solution at 4, 6, and 8 mL/kg/h for minimal,

moderate, and severe trauma, in addition to (b) the

estimated hourly maintenance fluids.4

Oxygen Transport

Hemorrhage interferes with normal tissue oxygenation by two mechanisms: (1) the anemic (ie,

inadequate oxygen-carrying capacity) and (2) the

hemodynamic (ie, inadequate tissue perfusion).

Anemia is rarely appreciated immediately after a

hemorrhage. This may be due to inadequate time

for equilibration or inadequate interstitial fluid reserves. However, even in the setting of severe

hemorrhage, reduced hemoglobin content of the

blood is rarely the cause of tissue hypoxia.5 For

example, a healthy, 20-year-old, male soldier (with

body surface area of 1.73 m2) arrives at a combat

support hospital within 1 hour of sustaining an

extremity wound. Medical personnel there estimate that he has experienced a 40% to 50% hemorrhage from the femoral artery. Fortunately, the

bleeding had been controlled at an aid station and

he had been resuscitated with 6% hetastarch and

lactated Ringer’s solution. On arrival at the combat

support hospital, his vital signs are stable and the

bleeding has stopped. His hemoglobin is determined to be 7 g/dL. Assuming a PaO2 (partial

pressure of oxygen in the arteries) of 95 mm Hg, a

hemoglobin saturation of 99%, and a normal cardiac output (C.O.) of 5 L/min, the arterial oxygen

content (CaO2) and oxygen delivery (DO2) of this

hypothetical casualty can easily be calculated:

CaO2 = 1.36 • (hemoglobin concentration)

• (hemoglobin saturation) + 0.003 (PaO2)

CaO2 = 1.36 • (7 g/dL) • (.99) + 0.003

• (95) = 9.71 mL O2/dL

C.O. • CaO2 = DO2

5 L/min • 9.71 mL/dL = 486 mL O2/min

Assuming a normal C.O. of 5 L/min, with a CaO2 of

9.71 mL/dL, this hypothetical patient can deliver

486 mL of O2/min or 281 mL/m2. This value exceeds the predicted basal O2 consumption rate of

250 mL/min. Under stress conditions, the basal

oxygen requirement may increase 2- to 3-fold. However, the cardiac output of most young, healthy

soldiers can increase 2- to 3-fold to keep up with

increased metabolic demand, provided that an adequate cardiac preload has been maintained.

This example demonstrates that (a) blood replacement is frequently unnecessary and (b) vol-
Hemorrhage, Shock, and Fluid Resuscitation

85

ume restoration with asanguinous plasma expanders is, at least initially, the key element. If the

circulating plasma volume is maintained, then the

metabolic consequences of severe hemorrhage can

be minimized. The critical point to be remembered

in this scenario is that the soldier’s hemorrhage was

not ongoing but had been stopped by appropriate

first aid. However, in the setting of unabated hemorrhage and shock (as indicated by hypotension,

tachycardia, mental-status changes, and diminished

or absent urinary output), the administration of

blood is essential and should not be withheld.

When combat casualties who are in shock arrive

at a medical treatment facility with surgical capabilities, medical officers should not underestimate

the amount of fluid required to reestablish a circulating blood volume compatible with survival. For

example, during the Vietnam War, soldiers who

required a blood transfusion received, on average,

2.5 L of blood and 2 L of crystalloid fluid during

their initial resuscitation and surgery.6 Even combat casualties who are no longer bleeding—who

have normal hemodynamic indices and have received what should be adequate restoration of red

blood cell mass on the basis of estimated blood

loss—frequently have a deficient red blood cell

mass when this is measured several days after the

resuscitative surgery.7

HYPOVOLEMIA

Vascular and visceral injuries secondary to missile wounds, fractures of the long bones, and crush

injuries are frequently accompanied by visible and

occult hemorrhage. The amount of blood lost will

not always be evident, as blood loss tends to

be overestimated with more-visible, superficial

injuries and underestimated with abdominal and

orthopedic injuries (see Chapter 20, Abdominal Injuries, and Chapter 21, Extremity Injuries). Intervention in the field and mobilization of extracellular fluid stores (transcapillary refill) may serve to

confuse the initial estimation of blood loss and

result in an underestimation of blood loss. The

classic parameters for the estimating the severity of

hemorrhage are often a useful starting point for

determining the rapidity and types of fluid administered, and for determining the response to resuscitation (Table 4-2). Supine hypotension in all combat casualties should be recognized as hypovolemia

that requires rapid and immediate fluid resuscitation.

Trauma victims presenting with a suspected mild

hemorrhage (Class I: suspected blood loss in the

absence of tachycardia or hypotension) require initial resuscitation with clear solutions, preferably

intravenous crystalloids. Resuscitation for moderate hemorrhage (Class II: tachycardia without

hypotension) should be initiated with crystalloid

or colloid solutions or both; however, in the presence of continued bleeding, early transfusion

therapy with packed red blood cells or whole blood

should be initiated. The presence of hypotension

(Class III or Class IV hemorrhage: tachycardia and

hypotension) requires immediate blood-volume

replacement with (a) packed red blood cells or whole

blood and (b) crystalloid solutions. Other causes of

TABLE 4-2

ESTIMATION OF HEMORRHAGE

Degree of Blood Loss Blood Vol. Heart Blood Pulse Respiratory Urinary Flow Mental

Hemorrhage (L) Lost (%) Rate Pressure Pressure Rate (mL/h) Status

Adapted with permission from Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians. Chicago,

Ill: American College of Surgeons; 1989: 72.

Class I < 1 < 15% < 100 Normal Normal or 14–20 > 30 Slight

increased anxiety

Class II 0.75–1.5 15%–30% > 100 Normal Decreased 20–30 20–30 Mild anxiety

Class III 1.5–2.0 30%–40% > 120 Decreased Decreased 30–40 < 15 Anxious and

confused

Class IV > 2.0 > 40% > 140 Decreased Decreased Rapid and Negligible Confused and

shallow lethargic
Anesthesia and Perioperative Care of the Combat Casualty

86

hypotension (eg, tension pneumothorax, cardiac

tamponade) should be sought after fluid resuscitation has begun.

In the combat setting, tachycardia is a useful, but

often an insensitive, indicator of hypovolemia. Just

how insensitive was one of the more interesting

findings of the surgical research unit that worked

during World War II. Data on the effects of shock on

heart rate were published in the seminal volume,

The Physiologic Effects of Wounds, published as part

of The Surgeon General’s official history of the U.S.

Army Medical Department in World War II (Table

4-3).8 The degree of shock in injured soldiers was

stratified not only by blood pressure but also by

measurement of blood volume. The table demonstrates that the differences between the heart rates

in soldiers with varying degrees of shock are so

small as to be useless for predictive purposes.

Subsequent studies on combat casualties have

confirmed that there may be no simple relation

between magnitude of hemorrhage and heart rate.9

Although the generalized discharge of the sympathetic component of the autonomic nervous system

following a precipitous fall in blood pressure leads

to tachycardia, the decrease in venous return to the

heart by unloading mechanoreceptors in the cardiac chambers, and especially the left ventricle,

leads to reflex slowing of the heart through an

efferent pathway that involves the parasympathetic

nervous system. Thus, hemorrhage activates two

different components of the autonomic nervous

system, and although tachycardia due to the sympathetic component usually predominates, vagal

slowing may also be seen.

In addition, other factors may confound any

relation between the observed heart rate and the

magnitude of blood loss. For example, atropine

administered in the field for chemical exposure,

fear, and pain makes the use of heart rate unreliable.

Trained athletes and infantry soldiers may tolerate

a substantial hemorrhage without manifesting

tachycardia or hypotension until they are severely

hypovolemic. When possible, performance of a tilttest will help to distinguish hypovolemia from other

causes of tachycardia.

It is important to recognize that heart rate and

blood pressure may normalize with initial resuscitation efforts, but this may not be indicative of

normal peripheral perfusion. Mixed venous blood

oxygen saturation may be the best single index for

assessing the adequacy of systemic perfusion.10

However, this determination requires a blood gas

analyzer, a device not usually available in forward

surgical hospitals (this subject is discussed more

fully in Chapter 5, Physiological Monitoring). Furthermore, a central venous line is required. Unfortunately, invasive arterial and central venous monitoring, although often desirable for fluid management, may not be easily managed in the combat

theater.

Traditionally, restoration of urinary output has

been used as a monitor of organ perfusion and as a

guide to fluid therapy. An indwelling urinary bladder catheter should be considered an essential monitor in all trauma victims. There may be no change

in hematocrit immediately following hemorrhage,

because only when transcapillary fluid refill occurs

(or when fluid resuscitation is initiated) does diluTABLE 4-3

RELATIONSHIP OF DEGREE OF SHOCK TO HEART RATE (106 CASES)

Degree of Shock

None (n=13) Slight (n=24) Moderate (n=34) Severe (n=35)

Reduction of Blood Volume (%) 14.1 ± 4.9 20.7 ± 4.1 34.3 ± 3.1 45.9 ± 4.6

Blood Pressure (m ± SD)

Systole 126 ± 11.9 109 ± 3.0 95 ± 4.9 49 ± 7.6

Diastole 75 ± 1.5 66 ± 2.7 58 ± 3.5 25 ± 5.8

Heart Rate (m ± SD) 103 ± 7.2 111 ± 3.4 113 ± 3.6 116 ± 3.3

(Range) (70–140) (88–150) (80–160) (60–144)

Data source: The Board for the Study of the Severely Wounded, North African–Mediterranean Theater of Operations. The Physiologic

Effects of Wounds. In: Beecher, HK, ed. Surgery in World War II. Washington, DC: US Army Medical Department, Office of The Surgeon

General; 1952: 34, 35, 56.
Hemorrhage, Shock, and Fluid Resuscitation

87

tion of the remaining red blood cell mass occur.

Thus, acute changes in hematocrit and hemoglobin

are not necessarily useful in evaluating ongoing

blood loss.

Venous Access

The initial management of all combat trauma

casualties must involve a team effort focusing on

combined assessment and intervention as indicated

by the immediacy of the situation. Casualties presenting with evidence of shock must quickly be

inspected for evidence of external hemorrhage. If a

site of major bleeding is found, appropriate first-aid

maneuvers designed to stop the bleeding (eg, direct

pressure) must be instituted immediately. Two or

more large-bore (preferably 14-gauge) intravenous

fluid cannulae must be established early in all casualties in shock, or those suspected of having injuries

that might lead to shock. Venous access can be

extremely difficult to obtain in the presence of

hypovolemia and dehydration. Additionally, access sites may be limited by the location and nature

of the traumatic injuries. Optimal sites for venous

cannulation in trauma victims include the antecubital, subclavian, saphenous, and femoral veins.

Surgical access (cutdown) may be required in

patients with severe hemorrhagic shock. The saphenous and antecubital vessels are convenient locations for cutdown cannulation. This approach allows the sterile intravenous extension tubing to be

inserted directly into the vessel to maximize delivery. A major disadvantage of the surgical approach

is the risk of infection.

Central venous access may be obtained via the

internal and external jugular veins, the subclavian

vein, and the femoral veins. Femoral access eliminates the risk of a pneumothorax (a recognized

complication of gaining venous access via the neck

and chest); however, the femoral site is remote from

the anesthesiologist during most surgical procedures. Also, penetrating intraabdominal injuries

may involve the inferior vena cava. In such cases,

resuscitation via the femoral vessels may contribute

to intraabdominal bleeding or be rendered ineffective by cross-clamping of the femoral vessel. The

subclavian vein is a useful site for trauma access;

however, this location carries a significant risk of a

pneumothorax. Both the subclavian and internal

jugular sites carry a significant risk of unintentional

arterial injury or cannulation.11 Major blood loss

has occurred following arterial injuries at both sites,

and the potential exists for an expanding hematoma

in the neck to compromise the airway. Techniques

for obtaining peripheral, central, and cutdown

venous access are well taught in the American

College of Surgeons’ Advanced Trauma Life Support course, which should be taken by all medical

officers.12

Intravenous Fluid-Delivery Systems

Some consideration must be given to ensuring

the availability of large-bore, fluid-administration

sets. The ideal set contains a large-surface-area

combination drip chamber and blood filter (170 μ),

dual vessel-access ports, and a hand-operated pumping chamber.

Large-caliber, high-efficiency, blood-warming

units are essential for large-volume resuscitation.

The Level 1 infusion system (manufactured by Level

1 Technologies, Inc., Rockland, Mass.) is a functional unit that provides rapid warming of intravenous infusions, through a counter-current warming

system, at high rates of flow (500 mL/min) (Figure

4-2). This system allows quick and effortless priming, and has an in-line air vent to prevent accidental

air emboli when used in conjunction with a presFig. 4-2. The Level 1 blood warming system is manufactured by Level 1 Technologies, Inc., Rockland, Mass.
Anesthesia and Perioperative Care of the Combat Casualty

88

sure infuser. These devices are being evaluated by

the U.S. Army Medical Department for use in its

field hospitals. The space required for the warming

unit and the disposable components, and the expense of the disposable components are disadvantages of the Level 1 fluid warmer.

Alternative methods for rapid warming of crystalloid solutions include using microwave ovens or

storing the solutions in warming ovens. The use of

microwave ovens for blood components is presently not recommended. Under no circumstances

should the fluid be infused at a temperature exceeding 40°C.

Pressure-assist, fluid-administration devices

(pressure bags) are helpful in speeding fluid delivery. Most of these are manually operated bladder

devices. Pneumatic infusers are currently marketed; however, under field conditions, the availability of compressed gas may limit their use. The

Biomed Spring Activated Infusion Pressor (manufactured by Migada, Inc., Burbank, Calif.) offers a

useful mechanical alternative. This spring-operated system provides a constant pressure and thus

a more stable rate of delivery. Complications secondary to pressure-assisted fluid administration

can occur (eg, venous air emboli, which may occur

with compression of the residual air in an exhausted

intravenous fluid bag). Air traps in blood-warming

sets and air vents (eg, Level 1 system) can help to

minimize this risk. Also, inverting the container

and venting the air prior to administration will also

reduce this risk. Some concern has been raised over

the potential for damage to cellular elements with

pressurized delivery systems, but the significance

of this concern remains to be clarified.

Blood-Salvage Techniques

Salvaging blood for intraoperative autotransfusion is becoming an increasingly important part of

routine anesthetic and surgical practice. Much of

the recent emphasis on blood salvage has arisen

over concerns about the safety of community autologous blood supplies, predominantly relating

to the transmission of the human immunodeficiency

virus. Although blood-salvage techniques can reduce the need for homologous transfusion, blood

salvage usually does not completely eliminate the

need for transfusion of homologous blood products

in major trauma. Currently, there are two principal

methods for salvaging blood from the operative

field. The simplest method involves collecting the

blood into sterile vacuum containers containing an

anticoagulant (citrate-phosphate-dextrose or heparin) and reinfusing the unwashed filtered blood

directly into the patient. The advantages of this

technique include low cost, simplicity, and minimal

requirements for storage or trained personnel. The

disadvantages are that procoagulants, bacteria, and

free hemoglobin will also be infused into the patient.13 This approach appears to be ideally suited

for use in field hospitals; unfortunately, the risks

and benefits involved with transfusing unwashed

blood have not yet been well delineated.

The alternative approach to blood salvage involves the collection of shed blood and processing

it through a cell-washing device prior to reinfusion.

These cell-washing devices, such as the Cell Saver 4

(manufactured by Haemonetics, Boston, Mass.) have

become increasingly efficient and automated (Figure 4-3). The drawbacks include the need for personnel training, equipment expense, the need for

expensive disposable plastic ware, and a time delay

during processing. Furthermore, the benefits of cell

washing, as opposed to the reinfusion of unwashed

blood, have not been clearly demonstrated to improve patient outcome. With both techniques, coagulation factors and platelets are lost, and there is

a risk of trauma to the cellular elements. Although

blood salvage is clearly beneficial in the manageFig. 4-3. The Cell Saver 4 is manufactured by Haemonetics,

Boston, Mass.
Hemorrhage, Shock, and Fluid Resuscitation

89

ment of elective surgery, the advantages of introducing this methodology into the care of the combat

casualty have yet to be demonstrated.

Intraosseous Fluid Infusion

Intraosseous fluid infusion has been advocated

in situations in which venous access is difficult or

impossible to obtain.14 This route of delivery is

particularly amenable in the pediatric population,

and because pediatric casualties always occur in

urban warfare, military anesthesiologists need to

be familiar with the technique. Intraosseous access

in adults is somewhat more difficult to obtain. This

is partly related to the replacement of the marrow

space by fat and partly related to the density of the

overlying bone. Recent experimental animal studies have demonstrated the benefits of intraosseous

infusion of a small-volume mixture of hypertonic

saline and dextran via the sternum. A sternal infusion device has been developed that could be placed

in the field with minimal training of medics, and

then utilized for fluid access.15 This approach is still

in the early phase of development and testing.

At present, the intraosseous approach in adults is

impractical and inadequately tested. Special needles

are required for this technique (bone marrow sets)

and the clinical utility in adults is unknown. Typically, the marrow space is entered by inserting a 15-

or 18-gauge iliac bone marrow needle into the medial aspect of the proximal tibia. The distal femur,

in the midline above the condyles, is an alternative

site. The medial malleolus has been used in patients

in cardiac arrest, in whom venous access is difficult.

This approach may prove useful for the administration of selected drugs. Unfortunately, the distal

tibia provides inadequate flow rates for it to prove

useful in the management of hypovolemia. Complications with intraosseous infusions are uncommon.16 The most common complication is that of

local extravasation. Local cellulitis and osteomyelitis

are fortunately rare (< 1%). Deaths have occurred

with the sternal approach secondary to unrecognized penetration of the thoracic cavity.17

RESUSCITATION FLUID SELECTION

Hypovolemia and hemorrhagic shock fall along

a continuum from mild to profound organ

hypoperfusion. As cardiac output falls, oxygen

transport to less crucial end-organ cellular elements

(eg, skin, muscle) may become progressively inadequate, contributing to anaerobic metabolism

and the accumulation of organic acids (eg, lactate). Homeostatic efforts (vasoconstriction) to preserve perfusion to the heart and brain inevitably

sacrifice perfusion to the kidneys, muscle, intestine,

and skin, leading to the classic manifestations of

shock. The eventual lethality of the shock state

probably results from the maintenance of this restricted perfusion pattern and progressive tissue

hypoxia and acidosis.18 Some evidence suggests

that blockade of the sympathetic nervous system

may reverse the vasoconstriction-induced acidosis

and improve survival after bleeding has been

stopped and blood volume restored.19–21 However,

a more effective and clinically relevant treatment

plan is to restore the circulating blood volume and

organ perfusion.

A variety of treatment regimens, including colloids, crystalloid solutions, whole blood, and blood

components, have been proposed (Table 4-4). Perhaps the best initial approach to the casualty with

evidence of a mild-to-moderate hemorrhage (10%–

30% of the estimated blood volume) is to rapidly

administer an intravenous fluid challenge of a

warmed, balanced, salt solution in 10- to 20-mL/kg

increments, depending on the severity of symptoms and ongoing blood loss. Repeated fluid challenges are administered until the desired hemodynamic response is obtained. Blood products should

be administered to keep pace with concurrent blood

loss and to maintain an acceptable hemoglobin level

(> 7 g/dL). When uncontrolled bleeding occurs,

isovolumic transfusion with fresh whole blood or

packed red blood cells, in conjunction with a crystalloid solution, is necessary.

Crystalloid Solutions

Although a variety of crystalloid solutions is

available, 0.9% sodium chloride or lactated Ringer’s

solution are reasonable first choices. Isotonic sodium chloride (0.9%) may be readily mixed with

blood products and is an excellent choice for volume resuscitation. However, it has the minor disadvantage of contributing to a hyperchloremic acidosis when large volumes of resuscitation fluid

must be used. Lactated Ringer’s solution has the

advantage of having a somewhat more physiological composition, providing elemental replacement

of calcium and potassium, and more physiological

concentrations of sodium and chlorine ions. A

disadvantage of lactated Ringer’s solution is its

relative incompatibility with blood products. The
Anesthesia and Perioperative Care of the Combat Casualty

90

TABLE 4-4

RESUSCITATION FLUIDS

Solution Advantages Disadvantages

0.9% NaCl Inexpensive Nonphysiological Na+ and Cl– concentrations

Compatible with blood Contributes to interstitial edema

Replenishes ECF space Large volumes required for replacement of

Increases GRF blood loss (> 3-fold estimated blood loss)

Lactated Ringer’s Inexpensive Same as those for NaCl

Physiological electrolyte concentrations

Increases GFR

Replenishes ECF space

5% Albumin Replaces plasma loss volume for volume Expensive

 (MW 6•104) Provides rapid expansion of the intra- Redistributes into the interstitial fluid space

vascular space with less volume relatively quickly (compared to other colloids)

May aggravate edema in leaky capillary states

6% Hetastarch Same as those for 5% albumin Expensive

(Hespan, Dupont) Provides a more persistent expansion May interfere with coagulation cascade if

(MW 104–107) of the intravascular space, relative to > 20 mL/kg is administered

 albumin

Plasma volume expansion may persist

> 24 h

5% Plasma Protein Resembles albumin Similar to albumin, somewhat less osmotically

Fraction (83% active

albumin) Contaminating plasma proteins may produce

 hypotension with rapid administration

Dextran 40 (average Provides rapid expansion of the intra- Risk of anaphylaxis 0.5%–5%

MW 4•104) vascular space with a small volume May contribute to renal failure

Reduces incidence of thromboembolism Interferes with platelet function and clotting

Risk of bleeding with > 1.5 g/kg/d

Interferes with blood cross-matching

May produce osmotic diuresis

Dextran 70 (average Same as those for dextran 40 Same as those for dextran 40

MW 7•104) Larger MW confers a greater duration

of plasma volume expansion

HDS Very rapid restoration of intravascular Same as those for dextran 40

volume with a small volume Brief hypotension with rapid infusion

Small volume makes field use easier Hypernatremia, especially if used in dehydrated

casualties

calcium content of lactated Ringer’s solution may

activate the coagulation cascade in blood products;

however, slight dilution of packed red cells with

lactated Ringer’s solution has not been shown to

cause a problem.22 The lactate content of lactated

Ringer’s solution may aggravate the correction of

the ongoing metabolic acidosis in individuals suffering from profound acidosis or ketoacidosis.

Under most circumstances, however, when organ

perfusion has been restored, the liver is quite capable of metabolizing the lactate load; the problem

is, therefore, rarely of concern.23

Intravenous fluids containing dextrose (glucose)

are rarely indicated and are potentially harmful in

the management of trauma casualties. The stress

response induced by major trauma or surgery

frequently contributes to a normal or an elevated

blood glucose level. Rapid administration of large

volumes of glucose solutions during resuscitation

may lead to an osmotic diuresis, confounding efECF: extracellular fluid; GRF: glomerular filtration rate; HDS: hypertonic saline (7.5%) and dextran 70 (6%); MW: molecular weight
Hemorrhage, Shock, and Fluid Resuscitation

91

forts to restore the intravascular deficit. Hyperglycemia has also been linked to a poorer neurological outcome among victims of trauma, cardiac arrest, and stroke.23–25 Glucose may be included in

maintenance fluids during the postresuscitation

phase.

Colloid Solutions

The use of colloid-containing intravenous solutions in the management of trauma and surgical

patients remains a source of controversy and is

thoroughly discussed in other textbooks26,27 and in

Chapter 24, The Syndromes of Septic Inflammatory

Response and Multiple Organ Dysfunction. Historically, the only colloids that were available in the

military for field use were albumin and plasma.

More recently, the dextrans and hydroxyethyl starch

(Hespan, manufactured by Du Pont Pharmaceuticals, Wilmington, Del.) have become widely available and are used by some civilian paramedic rescue squads for field resuscitation of casualties in

hemorrhagic shock. The most significant drawback

to these agents is their cost, which is excessive

relative to crystalloid solutions. The attractive features of the colloids include

• rapid repletion of the intravascular compartment with a smaller fluid volume,

• a more-prolonged expansion of the plasma

volume, and

• less peripheral edema.

Some have suggested a reduced risk of increased

intracranial pressure as another attractive feature

of colloids. This may be true in comparison to

lactated Ringer’s solution; however, the effects of

isotonic solutions (eg, normal saline) on intracranial pressure appear comparable to those of albumin.28

Colloid solutions produce an increase in the intravascular colloid oncotic pressure and may draw

interstitial water into the intravascular compartment.29,30 Thus, the plasma volume expands in

excess of the administered fluid volume. Conversely, in “leaky capillary” states (eg, burns, sepsis,

the adult respiratory distress syndrome), the colloids can traverse the endothelial barrier and contribute to the formation of pulmonary and peripheral edema. Although abnormal capillary membranes are not likely to be present during the initial

treatment of most combat casualties, other disadvantages of colloid solutions that argue against

their use include the following:

• the potential for impaired coagulation,

• interference with cross-matching of blood,

• increased viscosity,

• a transient fall in ionized calcium levels

(which albumin may produce), and

• the potential for a relative reduction in

glomerular filtration.

The reduction in glomerular filtration rate probably

reflects (a) the depletion of the interstitial fluid

compartment through third-space losses and (b) the

inability of colloids to replace the loss.30 A relatively hyperoncotic state may result. Crystalloids

are better suited to improving glomerular filtration.

Patients with compromised glomerular filtration

may be placed at increased risk of renal failure if

resuscitated with a dextran solution.31 In hypovolemic patients, renal tubular obstruction may

develop due to precipitation of the dextran in the

tubules.

In circumstances where blood loss is substantial

and continuing, dextran and hetastarch should be

used cautiously. Dextran interferes with platelet

adhesion and may aggravate blood loss.32 Hetastarch, when used in large cumulative volumes, has

been shown to produce a coagulopathy, probably

by interfering with Factor VIII activity.33 Clinical

case reports have linked bleeding catastrophes to

the use of hetastarch in quantities greater than 20

mL/kg.34 Life-threatening anaphylaxis can occur

with the dextrans and hetastarch. The overall risk

of anaphylaxis appears to be on the order of 0.5% to

5% with the dextrans and 0.08% with hetastarch.33

Hypertonic Solutions

Hypertonic saline solutions, alone or in combination with concentrated colloid solutions, have become the focus of intense interest over their possible use as small-volume resuscitation fluids in the

field. The primary advantage of hypertonic solutions compared to conventional fluids for field resuscitation is logistical: much less hypertonic fluid

is required for an equivalent degree of resuscitation—thus, the load of the combat medic is reduced.

The U.S. Army Medical Research and Materiel Command at Fort Detrick, Frederick, Maryland, has had

an ongoing research program into the development

and clinical application of a hypertonic saline dextran solution (7.5% sodium chloride and 6% highmolecular-weight dextran 70). This solution, when

used in animal models for hemorrhagic shock, has

effected dramatic improvements in hemodynamic

parameters and survival following a hemorrhage
Anesthesia and Perioperative Care of the Combat Casualty

92

that would otherwise have been lethal.35 Limited

field trials using human volunteers have documented the beneficial hemodynamic effects when

hypertonic saline dextran is administered by paramedics; however, improved patient outcome has

not yet been demonstrated convincingly.36,37 One

reason for this could be the rapidity with which

most patients were transported to hospitals and

received definitive care.

Hypertonic saline produces a rapid expansion

of the intravascular space by drawing extracellular and intracellular water into the vascular

compartment. Hypertonic saline alone produces

short-lived improvements in hemodynamics, as

the sodium tends to redistribute rapidly. The addition of a concentrated colloid solution (eg,

dextran, hetastarch) increases the duration of the

plasma volume expansion and improves survival

in animal models.35 However, two recent clinical

investigation studies involving traumatized humans show no added benefit from dextran compared with 7.5% saline alone.38,39 Subsequent volume replacement with isotonic, balanced salt solutions is essential to maintain organ perfusion as

the effects resolve, and to reverse the relative hypernatremic/hyperoncotic state.40 Hypertonic saline

resuscitation may offer additional advantages in

the management of head-injured, hypovolemic casualties by minimizing elevations in intracranial

pressure and by improving the cerebral-perfusion

pressure.41 While the benefits are clearly evident in

the short term (hours), the long-term benefits or

disadvantages of hypertonic solutions on cerebral

perfusion and neurological outcome need to be

demonstrated.

One important hazard associated with the use of

hypertonic-resuscitation measures in the field is the

risk of promoting further exsanguination and dehydration. Improvements in blood pressure and cardiac output in casualties with uncontrolled bleeding may increase the rate of blood loss, leading to

further loss of oxygen-carrying capacity, progressive acidosis, and increased morbidity. Data from

studies42 with experimental animals appear to support these conclusions. Thus, the administration

of hypertonic solutions in the presence of uncontrolled hemorrhage, and in the absence of guaranteed, short-term delivery of definitive supportive

and surgical treatment, may be contraindicated. Of

course, the same stricture applies to resuscitation

with any fluid that raises blood pressure, including

lactated Ringer’s solution. Further study is needed

on this issue.

At present, and under most conditions, crystalloid solutions appear to be the resuscitation fluid of

choice. Perhaps some combination of colloid and

crystalloid solutions will prove to be the optimal

approach. Colloid solutions should probably be

avoided during the initial resuscitation (ie, the first

24 h) of victims with extensive burn injuries, casualties suffering from the adult respiratory distress

syndrome, and in casualties suffering from preexisting dehydration. Hypertonic solutions may have

a role in the immediate resuscitation of hypovolemic

trauma casualties, provided continued volume support with isotonic solutions is available. Colloid

solutions or hypertonic saline may prove particularly useful prior to the induction of anesthesia in

conscious, hypovolemic casualties, or in hypovolemic casualties with head injuries who require

immediate surgery. Of course, the development of

an oxygen-carrying solution—such as a stroma-free

hemoglobin solution—which, in contrast to blood,

could be taken into the field by the medic, would be

an important step forward in our ability to treat the

combat casualty.

SUPPLEMENTAL THERAPEUTIC MEASURES

Although control of bleeding and rapid infusion

of crystalloid fluids and blood are the essential

steps that must be taken if the combat casualty in

shock is to be salvaged, a variety of supplemental

therapeutic measures have been suggested in the

past; in some instances, they may play an important

role. The use of other measures, such as steroid

theroid therapy in the management of head trauma,

continues to be controversial and unresolved. However, in the absence of Addison’s disease, adrenocorticoids are unlikely to be beneficial in the management of hypovolemic shock.

Patient Position

Conventional management of hypotensive

trauma victims frequently involves placing the patient in the head-down (Trendelenburg’s) position

to improve venous return to the heart (Figure 4-4).

In otherwise normovolemic subjects experiencing

hypotension (ie, those in neurogenic shock), lowering the head or elevating the legs may facilitate

venous return. However, studies43 of subjects with

hemorrhagic shock have failed to demonstrate

consistent hemodynamic improvement from
Hemorrhage, Shock, and Fluid Resuscitation

93

Fig. 4-4. The data shown in this phasic pressure and flow diagram were obtained in an anesthetized swine

instrumented with an aortic flow probe for measuring cardiac output (CO) and pressure transducers in the proximal

aorta (AP) and left atrium (LAP). When the animal’s hind legs were raised abruptly, cardiac output, aortic pressure,

and left atrial pressure were transiently elevated. Previously, 50% of the animal’s circulating blood volume had been

removed. Cardiac output remained elevated when the legs were lowered, suggesting that the blood that transfused

into the central circulation when the extremities were raised has not yet been redistributed back to the legs. The fall

in aortic pressure caused by lowering the legs may mean that the hydrostatic pressure head above the site of the pressure

catheter is itself a factor in determining the magnitude of the measured pressure. If applicable to humans in shock, data such

as these suggest that Trendelenburg’s position may be hemodynamically beneficial. Source: Medical Audio Visual

Aids Division, Letterman Army Institute of Research, Presidio of San Francisco, Calif. File Number 229-82-1, 1983.

kg) and the augmented cardiac output secondary

to the increased venous return is transient (Figure

4-5). Maintenance of blood pressure with this

device probably is the result of a mechanical increase in resistance in the compressed tissue and

therefore is purchased at the cost of decreased perfusion of already ischemic tissue. Clinical studies46

have demonstrated significantly reduced survival

in patients treated with the pneumatic antishock garment when the site of hemorrhage is in the

chest and, therefore, is not compressed by the device. This is not surprising given that any increase

in blood pressure will simply increase the rate of

hemorrhage. If the pneumatic antishock garment

has any utility in combat casualty care, it is in

stabilizing fractures of the pelvis and the long bones

of the legs. In this setting, the device may help to

reduce ongoing blood loss and therefore permit

hemodynamic stabilization prior to definitive intervention.

Supplemental Oxygen

The routine administration of supplemental oxygen to trauma casualties may be beneficial in some

victims, in that multiple or massive injuries (eg,

splinting, flail chest, fat emboli) are often associated

with impaired oxygenation. However, expectaTrendelenburg’s position, and this position may

have an adverse impact on cardiac output and blood

pressure.44 Furthermore, Trendelenburg’s position

may produce adverse consequences in the hypovolemic, head-injured victim by increasing intracranial pressure and reducing the cerebral perfusion

pressure. Most of these problems can be avoided

simply by elevating the legs to facilitate venous

return, without placing the head in a dependent

position.

Pneumatic Antishock Garment

The use of the pneumatic antishock garment (a

compression device first known as military

antishock trousers [MAST]) was introduced by the

U.S. Army during the Vietnam War. Until recently,

use of this garment was considered to be a standard

of practice but its use in the acute management of

hemorrhagic shock has now waned. The pneumatic

antishock garment appears to support the blood

pressure by a combination of increased systemic

vascular resistance and increased venous return.45

There seems little doubt that proper use of the

pneumatic antishock garment results in an

autotransfusion of blood from the compressed tissue in the lower half of the body into the central

circulation, but the actual volume is small (2–3 mL/
Anesthesia and Perioperative Care of the Combat Casualty

94

Fig. 4-5. The phasic pressure and flow data shown in this figure were obtained in an anesthetized swine instrumented

with an aortic flow probe for measuring cardiac output (C.O.), a flowprobe inserted into the inferior vena cava (IVC),

and pressure transducers in the proximal aorta (AP) and right atrium (RAP). A pneumatic antishock garment

especially designed for application to a large swine was applied around the animal’s lower trunk and hind legs. The

upper panel shows pressure and flow transients associated with abrupt inflation and deflation of the pneumatic

antishock garment. A bolus of blood is translocated through the inferior vena cava into the heart (equivalent to about

2 mL/kg, or 100 mL total), but cardiac output actually falls. Possibly this is due to an increase in arterial impedance

caused by the external compression. The lower panel shows the effects of inflating the pneumatic antishock garment

after 50% of the animal’s circulating blood volume is removed: both cardiac output and aortic pressure rise. Reprinted

with permission from Bellamy RF, DeGuzman LR, Pedersen DC. Immediate hemodynamic consequences of MAST

inflation in normo- and hypovolemic anesthetized swine. J Trauma. 1984;24:892.

duced temperatures. Thus, hypothermia (< 37°C)

may be beneficial in reducing oxygen consumption

in individuals with reduced oxygen-carrying capacity if blood transfusion cannot be provided, but

this approach to managing the seriously injured

combat casualty can only be considered speculative.

Intraarterial Infusion

Intraarterial infusion was advocated during the

Korean War because it appeared to provide the

potential for more-rapid volume replacement, compared with the intravenous routes then being used.

However, clinical evidence failed to show any significant advantage of this route over more conventional intravenous approaches, and its complexity

argues against its use today.

tions of improved tissue oxygenation in the presence of hypovolemic shock are unrealistic: hemoglobin oxygen saturation in the typical young

combat casualty—who is usually hyperventilating

because of the injury—is already maximal.

Furthemore, the added amount of dissolved oxygen in the plasma caused by breathing supplemental oxygen is too small to be of importance. Until the

circulating blood volume is restored, supplemental

oxygen is unlikely to reverse the anaerobic metabolism in poorly perfused tissues.

Therapeutic Hypothermia

Reductions in body temperature are associated

with a reduced metabolic rate: approximately 13%

for every 1°C decrease in temperature.47 In addition, oxygen solubility in plasma increases at re-
Hemorrhage, Shock, and Fluid Resuscitation

95

Vasopressors

Efforts to support the arterial blood pressure

through the administration of vasoconstrictors are

mentioned here only to be condemned. Intense vasoconstriction is the typical homeostatic response to

hemorrhagic shock and may be primarily responsible

for the adverse consequences of hypovolemia (eg,

acidosis, tissue hypoxia). Pharmacological support

of the blood pressure with vasoconstrictors will

only aggravate the reduction in tissue perfusion by

decreasing cardiac output, and will contribute to the

progressive acidosis. The benefits of transiently supporting the blood pressure with vasoconstrictors,

until volume replacement or control of bleeding is

possible, have not been carefully evaluated.

Vasodilators

At face value, the administration of vasodilators

to a hypovolemic patient would seem to be grossly

inappropriate. However, numerous animal studies19–21—using fixed-pressure shock models of the

Wigger’s type, involving the use of epidural anesthesia or the administration of adrenergic antagonists in the presence of hemorrhagic shock—have

demonstrated both reductions in the severity of the

systemic acidosis and improved survival. The beneficial effects of sympathetic antagonism are related to a reversal of the reflex vasoconstriction

associated with hypovolemia. Tissue oxygenation

and perfusion, albeit reduced, are maintained at

levels adequate to reduce the progression of the

acidosis. However, the beneficial application of

central neuraxis anesthesia has not rigorously been

evaluated in the clinical setting. Case reports have

appeared in the literature; however, it is impossible to draw valid conclusions based on a limited

number of uncontrolled reports. Conventional

wisdom has dictated the avoidance of spinal and

epidural anesthesia in hypovolemic and bleeding

patients. Further study clearly is needed.

CONDITIONS PECULIAR TO RESUSCITATING COMBAT CASUALTIES

The conditions of the battlefield, which are so

unlike those encountered in civilian practice, can create unique problems for military anesthesiologists. Not only are combat injuries quite different

from those encountered in civilian practice, but the

propensity for environmental hazards to become important sources of comorbidity must also be kept in

mind.

Hyperthermia and Dehydration

Military conflicts frequently occur under adverse

climatic conditions. Elevated ambient temperatures, physical exertion, and inadequate supplies

on the battlefield can combine to contribute to the

development of heat injury and dehydration. Coincident trauma and hemorrhage in the setting of

preexisting dehydration and volume contraction

will adversely influence survival. Elevated body

temperature and hypotension will accelerate the

progression to renal failure and contribute to the

development of rhabdomyolysis. Rapid replacement of the intravascular and extracellular fluid

space with isotonic, balanced, salt solutions is key

to reversing this life-threatening process. Hyperoncotic

colloid or hypertonic saline solutions are relatively

contraindicated in casualties suffering from dehydration. The hyperosmotic state will adversely impact on

glomerular filtration and further deplete the extracellular and intracellular fluid spaces.

Hypothermia

Hypothermia is a common problem afflicting

trauma victims. The pathophysiology of hypothermia affects virtually all organ systems, and is discussed in detail in Chapter 28, Systemic Hypothermia. Profound hypothermia (core temperature <

30°C) is associated with substantial reductions in

renal blood flow (75%) and glomerular filtration.48,49

Despite this, profoundly hypothermic victims become progressively dehydrated due to a cold-induced diuresis secondary to defective tubular

reabsorption. The urine produced is usually dilute,

contributing to the development of a relatively

hyperosmotic serum. Temperatures below 30°C

are associated with ventricular fibrillation.

Hyperkalemia and hyponatremia frequently occur

with hypothermia; however, specific treatment is

seldom necessary. Restoration of fluid deficits with

warm hypotonic solutions (lactated Ringer’s) is

generally all that is required. Metabolic acidosis

frequently develops as the patient is rewarmed.

Fluid resuscitation to restore and maintain perfusion will correct the acidotic state; however, some

may choose to treat with intravenous sodium
Anesthesia and Perioperative Care of the Combat Casualty

96

bonate. Colloids and hypertonic solutions are relatively contraindicated in this hyperosmotic state.

Thermal Burns

Fortunately, extensive burns are uncommon combat injuries in land warfare. They are much more

common as nonbattle injuries:

[A]lthough the incidence of combat-related burns

has historically been about 3%, in recent wars the

incidence is higher because mechanized modern

warfare—tanks and other armored vehicles—actually places soldiers at higher risk [than previously]

of being burned.... During the Yom Kippur War,

burns comprised 10.5% of all injuries; during the

Falkland Island Conflict, 18% of British casualties

were burned. Furthermore, medical officers should

know that in the United States military, burns and

inhalation injuries have always been far more important sources of morbidity and mortality in both

the navy and the air force than in the army.50(p350)

The fluid management of burn victims has been

well described elsewhere51 (also see Chapter 22,

Burn Injuries) and will only briefly be discussed

here. Ordinarily, burns involving more than 15% of

the total body surface area will require intravenous

fluid therapy. A number of treatment protocols

have been developed to predict fluid requirements

in the immediate and delayed phases of injury.

However, as with any regimen, any given patient

may require more or less fluid. Parameters of adequate organ perfusion (eg, urinary output) provide the most accurate indicators with which to

guide fluid therapy.

Most authorities divide the fluid resuscitation of

burned patients into two phases: the initial 24 hours

and after the initial 24 hours. During the initial 24

hours, burn victims experience a generalized increase in capillary permeability that involves, in

addition to the burned areas, normal capillary beds.

This increased permeability has led some authorities52,53 to suggest that colloid solutions be avoided

in most patients during the initial 8 to 24 hours; the

concern is that protein loss into the extracellular

space will accelerate edema formation.51 This effect

is particularly evident during the initial 24-hour

period. Isotonic crystalloids will lead to interstitial

edema, but they also improve glomerular filtration

and allow for replacement of evaporative losses.

Hypertonic solutions have been touted to maintain

the intravascular compartment with minimal

edema.40 However, careful monitoring of serum

sodium is necessary to avoid hypernatremia. In the

absence of data demonstrating a clear improvement

in survival with any particular solution, it is reasonable to emphasize the use of isotonic crystalloids

during the initial 24 hours after the burn. The

revised Brooke formula54 recommends administering 2 mL of lactated Ringer’s solution per kilogram

of body weight per percentage of total body surface

area burned. Of the amount estimated to be required during the first phase, one half should be

administered during the initial 8 hours, with the

remaining volume dispersed over the next 16 hours.

The Rule of Nines55 is a useful indicator for estimating the percentage of body surface area burned:

• head and neck, 9%;

• anterior and posterior trunk, 18% each;

• upper extremities, 9% each;

• lower extremities, 18% each; and

• perineum, 1%.

After the initial 24 hours, colloid solutions are

clearly beneficial for restoring the plasma oncotic

pressure. Plasma proteins continue to be lost, not

only into the burned areas but also owing to dilution and the patient’s general catabolic state. Albumin solutions should be administered to maintain

the plasma albumin concentration at 2.0 to 2.5 g/dL

to support the plasma oncotic pressure.51 Evaporative losses may be replaced with hypotonic dextrose solutions during this period. During this

second phase, the requirement for sodium replacement generally declines and the risk of hypernatremia arises secondary to free-water loss via

evaporation and urine.

Hemorrhagic Shock and Head Injury

Severe head injury coexisting with hypovolemic

shock is an ominous combination (this subject is

discussed in greater detail in Chapter 16, Neurological Injuries). Cerebral edema or compression

by an expanding intracranial hematoma, or both,

produce an elevation in intracranial pressure.

Hypotension secondary to hemorrhage contributes

to further decline in the cerebral perfusion pressure

and thereby potentiates ischemic injury. Improvement of the mean arterial pressure with fluid resuscitation may lead to further increases in intracranial

pressure, secondary to increased cerebral blood

volume and progressive cerebral edema. Resuscitation with hypotonic fluids, especially dextrose

solutions, is contraindicated. Unfortunately, lactated Ringer’s solution is relatively hypotonic and

may contribute to increased cerebral edema. Col-
Hemorrhage, Shock, and Fluid Resuscitation

97

bicarloid solutions have been advocated; however,

with diffuse injuries, the blood–brain barrier may

be damaged, contributing to interstitial leakage of

colloid and worsening edema in the area of injury.

Because of their adverse interactions with the coagulation system, the dextrans and hetastarch solutions must be used with caution in the setting of

intracranial hemorrhage. Isotonic crystalloid solution (0.9% NaCl) does not accelerate brain edema

and may be the optimal resuscitation fluid.28

The Chemically Contaminated Casualty

Although the anesthetic management of casualties of chemical warfare agents is discussed in detail

in Chapter 30, Anesthesia for Casualties of Chemical Warfare Agents, and elsewhere, several brief

points on the fluid management of the chemically

injured casualty will be outlined here. The risk of

exposure to chemical weapons continues to persist

throughout the world, particularly in third-world

nations, as witnessed by the use of chemical weapons on civilian and military targets during the Iran–

Iraq War. Combat casualties in high-risk chemical

environments may present a confusing diagnostic

picture if chemical protective treatments (atropine,

pyridostigmine) have been used. Atropine-induced

tachycardia and the associated autonomic effects

may present a picture easily confused with

hypovolemia. Certain incapacitating agents (eg,

quinuclidinyl benzylate) may produce similar effects.

Pyridostigmine, an acetylcholinesterase inhibitor, was

provided to many troops as a chemical protectant

during the Persian Gulf War. Pyridostigmine tends to

produce bradycardia and may adversely interact

with the compensatory response to hemorrhage.

Fluid replacement is an important component in

the management of blister agents (ie, mustard).

Casualties exposed to blister agents may present

with considerable cutaneous denuding and subsequent fluid loss. Treatment requires aggressive

fluid management, similar to the treatment of thermal burns. Choking agents (eg, phosgene, chlorine), which may cause alveolar capillary injury,

represent the opposite end of the spectrum, in that

strict fluid management is needed to avoid contributing to the development of noncardiac pulmonary

edema. Because careful fluid management may not

be easily accomplished in patients with multiple

trauma who are also exposed to choking agents,

supportive therapy, including mechanical ventilation, may be needed in this population.

SUMMARY

Combat injuries associated with hemodynamic

instability should be regarded as hypovolemic until

proven otherwise. The rapid attainment of largebore venous access and the initiation of fluid resuscitation should occur simultaneously with evaluation of the casualty’s injuries. The administration of

fluids—colloid or crystalloid—should be guided by

the normalization of hemodynamic indices and especially by evidence of good peripheral perfusion

(eg, high urinary output). Coexisting medical concerns peculiar to the battlefield may create confusion in the interpretation of the physiological response to intervention. Military healthcare

providers must be aware of the medical implications associated with environmental and chemical

concerns of the combat theater.

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28. Kaieda R, Todd MM, Warner DS. Prolonged reduction in colloid oncotic pressure does not increase brain edema

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31. Mailoux L, Swartz CD, Capizzi R, et al. Acute renal failure after administration of LMW dextran. N Engl J Med.

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32. Weiss HJ. The effect of clinical dextran on platelet aggregation, adhesion, and ADP release in man: In vivo and

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33. Mishler JM. Synthetic plasma volume expanders—Their pharmacology, safety and clinical efficacy. Clinics in

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34. Cully MD, Larson CP, Silverberg GD. Hetastarch coagulopathy in a neurosurgical patient. Anesthesiology. 1987;66:706.

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39. Vassar MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injuried patients with 7.5%

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40. Monafo WW, Halverson JD, Schectman K. The role of concentrated sodium solutions in the resuscitation of

patients with severe burns. Surgery. 1984;95:129–134.

41. Prough DS, Johnson JC, Stump DA, et al. Effects of hypertonic saline versus lactated Ringer’s solution on

cerebral oxygen transport during resuscitation from hemorrhagic shock. J Neurosurg. 1986;64:627–632.

42. Gross D, Landau EH, Klin B, et al. Quantitative measurement of bleeding following hypertonic saline therapy

in “uncontrolled” hemorrhagic shock. J Trauma. 1989;29:79–83.

43. Taylor J, Weil MH. Failure of the Trendelenburg position to improve circulation during clinical shock. Surg

Gynecol Obstet. 1967;124:1005–1010.

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46. Mattox KL, Bickell W, Pepe PE, et al. Prospective MAST study in 911 patients. J Trauma. 1989;29:1104.

47. Michenfelder JD, Uihlein A, Daw EF, et al. Moderate hypothermia in man: Haemodynamic and metabolic

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48. Vandam, LD, Burnap, TK. Hypothermia. N Engl J Med. 1959;261:546.

49. Hervey GR. Hypothermia. Proc R Soc Med. 1973;66:1055.

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51. Demling RH. Fluid replacement in burned patients. Surg Clin North Am. 1987;67:15–30.

52. Baxter CR. Fluid volume and electrolyte changes in the early post-burn period. Clin Plast Surg. 1974;1:693–709.

53. Demling RH, Kramer GC, Gunther R, et al. Effect of non-protein colloid on post-burn edema formation in soft

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1953;152:1309.

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Department of Defense, Government Printing Office; 1988: 37.
Physiological Monitoring

101

Chapter 5

PHYSIOLOGICAL MONITORING

HERMAN V. DEVERA, M.D.*

INTRODUCTION

MONITORS IN THE ECHELONS OF CARE

First and Second Echelons

Third Echelon

Fourth Echelon and Higher

SYSTEMIC MONITORING

Hemostasis and Coagulation

Cardiovascular System

Respiratory System

Renal System

Nervous System

Temperature

COMPUTERS IN ANESTHESIA

SUMMARY

*Formerly, Lieutenant Colonel, Medical Corps, U.S. Army; Department of Anesthesiology, Walter Reed Army Medical Center, Washington,

D. C. 20307-5001; currently, Chief, Anesthesia Services, South Valley Hospital, 9400 No Name Uno, Gilroy, California 95020
Anesthesia and Perioperative Care of the Combat Casualty

102

INTRODUCTION

Physiological monitoring of combat casualties is

often compared unfavorably with monitoring as it

is done in civilian trauma situations. However,

those who make this comparison are usually not

cognizant of the significant differences between the

management of trauma in civilian versus military

settings. Especially important are the severe constraints that logistics place on the availability of

monitoring equipment and the vulnerability of sophisticated monitors to the rough-and-tumble environment of combat zone hospitals. Another important difference is the number of casualties needing

care: mass casualties are all too common in wartime.

The type of monitoring for anesthesia and surgery in the field depends on the echelon of care (the

casualty flow through the echelons of care is illustrated on page xv in the opening pages of this book).

The spectrum extends from the austerity of the

battalion aid station (first echelon) and the medical

company (second echelon) through the intermediate capability of mobile army surgical and combat

support hospitals (third echelon) to the complexity

found in general hospitals and in medical centers in

the continental United States (fourth echelon).

Another factor determining the sophistication or

even the possibility of monitoring will be the number of casualties requiring care. Obviously, the

number of casualties is beyond the control of an

individual medical unit. In a mass casualty situation, the overriding goal will be to use the available

monitoring resources to do the greatest good for the

largest number of casualties. The goal of monitoring then becomes one of deciding who needs monitoring and which monitoring devices to use. The

standards of care seen in medical centers, or even in

small community hospitals, in the continental United

States may have to be altered to conform to the

reality of the battlefield. Although the standards

applied on the battlefield may be unfamiliar to

those trained in a modern medical facility equipped

with the latest technical devices, this does not mean

that medical care in the field is inadequate.

Military trauma anesthesiologists must resist the

tendency to become dependent on sophisticated

devices such as monitors. Extremes of temperature;

delays; and damage to equipment due to transport,

dust, or other environmental conditions may all

require innovative approaches to monitoring the

combat casualty. Flexibility in using more basic

(low-tech) monitors is also desirable. The U.S. Army

Medical Department should ensure that anesthesia

care providers play a role in helping logisticians

decide which equipment should be available in

field hospitals.

This chapter is divided into two sections. The

first deals with the type of monitoring likely to be

found in medical treatment facilities from the first

through the fourth echelons; the second section

deals with the monitors used to evaluate the various body systems. Wherever possible, the principles of monitoring are related to the practical

aspects of field anesthesia care.

MONITORS IN THE ECHELONS OF CARE

The monitors that military anesthesia providers

can expect to find vary with the level of care from

austere through intermediate to complex (Table 5-

1). Each unit will, no doubt, modify the list of

equipment supplied. Specifically, individual military trauma anesthesiologists will likely go to considerable lengths to obtain (from their colleagues)

monitoring equipment not officially included in

their units’ Table of Organization and Equipment.

First and Second Echelons

Austere conditions prevail at unit- and divisionlevel medical facilities of the first and second echelons as well as forward surgical teams deployed

below corps. Although only the most basic devices

for monitoring casualties will be found at these

levels of care, initial surgery to make the casualty

transportable may be necessary. Ideal circumstances

would allow monitoring of pulse, ventilation, oxygenation, and blood pressure during monitored

anesthesia care or general or regional anesthesia.

However, in austere battlefield conditions, general

anesthesia will be provided in emergent situations

only, and will most likely be provided via the drawover system and not the portable anesthesia machine. Most monitoring will be for procedures

carried out with local or possibly some form of

regional anesthesia.

Monitoring at the first and second echelons may

consist of recording only vital signs (blood pressure, respirations, and heart rate) and the physical

examination. The monitoring equipment available,

which needs to be sturdy and transportable, may be
Physiological Monitoring

103

limited to a manual blood pressure cuff and a stethoscope. Whether pulse oximetry can be used will

most likely be determined by the availability of

electricity to run or charge the equipment. Pulse

oximetry would be highly valuable at first- and

second-level medical treatment facilities.

If there is a threat that the enemy will use chemical or biological agents, both the providers of care

and the casualties are in full mission-oriented protective posture (MOPP) gear. Obviously, any monitoring, other than possibly a cursory mental-status

examination, may have to wait until the casualty

has been decontaminated. Ambient noise may limit

the use of the stethoscope to just determining the

presence of heart sounds.

Blood pressure may have to be taken by merely

documenting the point at which the systolic pressure becomes palpable or the needle on the aneroid

manometer begins to bounce. (Blood pressure can

be measured by inflating a manual cuff and slowly

letting the cuff deflate while watching for the needle

on the manometer to begin to bounce; this correTABLE 5-1

RECOMMENDED EQUIPMENT AVAILABILITY AND MONITORS REQUIRED

Equipment Available Physiological Parameter Monitor Required

Austere Hemodynamics Manual blood pressure cuff

(First and second Precordial stethoscope

echelons) Temperature Thermometer

Intermediate Hemodynamics Blood pressure

(Third echelon) Precordial stethoscope

Electrocardiograph

Temperature Thermometer

Urinary output Foley catheter

Specific gravity

Sodium concentration

Respiration Pulse oximeter

Blood components Laboratory analyses (hematocrit, electrolytes,

blood urea nitrogen, creatinine, prothrombin

time/partial thromboplastin time, whole-blood

clotting time, activated clotting time)

Other Nerve stimulator

Oxygen analyzer

Capnography

Complex Hemodynamics Blood pressure

(Fourth echelon Precordial stethoscope

and higher) Electrocardiograph

A-line

Central venous pressure

Pulmonary artery catheter

Temperature Thermometer

Urinary output Foley catheter

Specific gravity

Sodium concentration

Respiration, airway Pulse oximeter

pressure, lung compliance Ventilator pressure gauges

Blood components Laboratory analyses (hematocrit, electrolytes,

blood urea nitrogen, creatinine, prothrombin

time/partial thromboplastin time, whole-blood

clotting time, activated clotting time)

Other Nerve stimulator

Oxygen analyzer

Capnography, Doppler
Anesthesia and Perioperative Care of the Combat Casualty

104

lates with the point at which one can begin to feel

the pulse.) This quick, accurate means of monitoring blood pressure may be the only method practicable. The bouncing needle on the sphygmomanometer also allows the observer to form an

impression of the patient’s heart rate. Heart rate

can be counted by either listening with a stethoscope or by taking the pulse. Subtle signs, such as

threadiness of pulse and crispness of heart sounds,

may provide information about the casualty’s volume status.

Third Echelon

The intermediate level of care includes mobile

army surgical and combat support hospitals. This

setting is more fixed than a medical company clearing station, but third-echelon hospitals must be

somewhat mobile also. These hospitals are designed to perform resuscitative surgery. General

anesthesia is available and, therefore, more elaborate monitoring equipment will be necessary. The

equipment found at this level must be sturdy, able

to withstand the multiple moves that may be required of a third-echelon hospital. Much of the

equipment used in this setting may arrive by some

expedient means (eg, being dropped by parachute

from a cargo plane). For these reasons, it is unlikely

that sensitive equipment such as mass spectroscopy

or other highly sophisticated monitors will be seen

at this level of care.

The portable anesthesia machine will probably

not contain an automated ventilator with disconnection alarms. The only “monitor” for sensing

disconnections of the anesthesia circuit will probably be the individual responsible for providing the

manual ventilation. Equipment at this level should

include electrocardiograph monitors, blood pressure cuffs, pulse oximetry, temperature-monitoring

devices, and perhaps even some form of capnography. The anesthesia machines (Ohio Model

855A Field Anesthesia Machine, manufactured by

Ohmeda, Inc., Madison, Wisc.) also should contain

an oxygen analyzer.

Pulse oximetry provides such valuable information that it should also be included at this level.

Although not standard equipment at this level, the

pulse oximeter will often be added as supplementary

equipment. The automated blood pressure cuff may

or may not be present. It is unlikely that more than

one or possibly two will be available—if present at

all at this level of care. The manual blood pressure

cuff will certainly find use at this level, whether in

the operating room or in the recovery areas.

Devices to monitor the casualty’s temperature

should also be included at this level of care. Adhesive, disposable, skin-temperature monitors will be

of little value at the third echelon. A more appropriate device is one able to measure axillary, oral,

esophageal, or rectal temperatures. Monitoring of

the skin temperature is unlikely to provide useful

information in casualties who are either receiving

large amounts of fluid or blood or are hypovolemic

because of blood loss.

The ability to monitor end-tidal carbon dioxide

(ETCO2) can be very useful, not only for verifying

endotracheal intubation but also for monitoring

carbon dioxide levels in casualties with head trauma.

Currently, these monitors are somewhat large and

are unlikely to be added as supplementary equipment. With improved technology and as they become more compact, capnographs will no doubt be

added even at the third echelon.

One additional method of providing anesthesia

that allows significant monitoring of the casualty’s

respiratory status (including oxygen requirements) is the use of closed-circuit anesthesia. This

method of providing anesthesia has many advantages:

• Changes in the patient’s oxygen utilization

are readily apparent.

• Oxygen waste is minimized (rather than

flows of 3–5 L/min, flows of 250–350 mL/

min or less are used).

• The use of a sophisticated vaporizer requiring calibration and high oxygen flows to

provide accurate delivery of anesthetic

agent is omitted; the potent anesthetic agent

can be delivered by merely introducing a

syringe containing a volatile anesthetic into

the breathing circuit.

• The total amount of inhalational anesthetic

agent used is decreased. This can be a most

significant factor if supplies are short.

The disadvantages of the use of this method of

providing anesthesia are few. It behooves providers of anesthesia, particularly those in the military,

to become familiar with this technique. Although it

may appear to be more time consuming (because

recent graduates of anesthesia training programs

lack familiarity with this technique), this technique

may be safer and more appropriate than the conventional vaporizer technique when supplies of

oxygen are short or when vaporizers are broken or

uncalibrated. Extremes of ambient temperature

(eg, in the desert) may also make the closed-circuit
Physiological Monitoring

105

anesthesia delivery technique more desirable (see

Chapter 8, Closed-Circuit Anesthesia, for a more

complete discussion of this subject).

Fourth Echelon and Higher

Complex levels of equipment are found at fourth

and higher echelons of care, including hospital ships

and hospitals along the chain of evacuation from

the theater of operations. The sophistication

of monitoring equipment is more like what anesthesia providers would expect to see at a civilian

or military community hospital or small medical

center. These are fixed facilities and would be

unlikely to move, once set up (the obvious exception being the hospital ship). For this reason, moreelaborate monitoring is likely to be found. At fourth

and higher echelons of care, automated blood pressure cuffs, pulse oximeters, automated ventilators

with disconnection alarms, capnographs, and

invasive hemodynamic monitoring devices (ie,

arterial and central lines for measuring central

venous and pulmonary artery pressure) will all be

found.

The use of these invasive monitoring devices

will, of necessity, depend on not only the individual

patient’s clinical situation but also on the number of

casualties requiring treatment. The great majority

of casualties will already have received resuscitative

surgery at mobile surgical or combat support hospitals; monitoring will be employed either in difficult

emergency cases requiring reoperative surgery or,

as is more common, in elective reconstructive operations. An inordinate amount of time cannot be

spent placing invasive monitors in all casualties;

nor is sophisticated monitoring necessary in most

operations (eg, delayed primary closure of softtissue wounds or reestablishment of gastrointestinal continuity). The intensity of monitoring will

have to be tailored to the needs of the casualty. This

philosophy, which is inherent in military triage, is

likely to be unfamiliar to most civilian personnel,

who are accustomed to providing all the care that

can be done, not just what must be done.

SYSTEMIC MONITORING

Anesthesia care providers will be faced with

difficult decisions regarding which monitors are

practical and necessary at the various echelons of

care. The decision regarding what monitoring devices to have available should be based on the level

of care to be provided, the expected needs of the

casualties, the durability of the equipment, and the

storage capability and mobility of the equipment.

Hemostasis and Coagulation

The first step in monitoring for hemostasis is the

evaluation of blood loss. This can be done by

directly measuring the volume of blood in the suction containers that were used to draw blood from

the operative field. Weighing, or estimating the

weight of, used surgical sponges is another method

of accounting for surgical blood loss. Besides monitoring for vascular integrity, monitoring of the coagulation system is also necessary.

Determining platelet count and function can easily be done at both the intermediate and complex

levels of care. A platelet count of 50,000 to 75,000

normal, functioning platelets may be inadequate

for intraoperative hemostasis. The Ivy bleeding

time test is used to measure platelet function. The

test is performed by making a standard, 9-mm–long

incision on the volar surface of the forearm while an

inflated blood pressure cuff on that arm is maintained at 40 mm Hg. The elapsed time required for

bleeding to stop is known as the bleeding time.

Normal bleeding times vary between 5 and 8 minutes.1

Several methods are available for monitoring

coagulation as well as for monitoring the coagulation status of casualties who have received therapeutic anticoagulation drugs. These methods include (1) heparin level measurements; (2) protamine

titration; (3) activated clotting times; and (4) other

tests such as prothrombin time, thrombin time, fibrinogen levels, and fibrin split product levels.

Heparin, a mucopolysaccharide, acts by stimulating the enzymatic activity of antithrombin III,

which inactivates the serine proteases in the coagulation scheme (factors II, VII, IX, and X). Approximately one individual in 2,000 has a physical condition (eg, liver disease, pregnancy, debilitating

illness) that depresses the antithrombin III level;

therefore, that individual may not respond to heparin. Serum levels of antithrombin III can be depressed by a variety of conditions; such deficiency

may be responsible for as many as 2% of clinical

cases of venous thrombosis.2

Devices used to estimate heparin level include

the automated protamine titration system and fluorometric analysis. The automated protamine titration method (Hepcon, manufactured by HemoTec,

Inc., Englewood, Colo.) uses protamine titration to
Anesthesia and Perioperative Care of the Combat Casualty

106

estimate heparin levels. Advantages of this method

include (1) the rapidity of obtaining results, (2) the

ease of use, and (3) the reliability of the results. The

disadvantages are (1) the cartridges expire in a short

time (60 d) and (2) the reagents require refrigeration.

The Hemochron system (manufactured by

Technidyne Corp, Edison, N.J.)—a simple, reliable,

automated activated clotting time test—was introduced during the mid-1970s; (unfortunately,

however, it is not available in field hospitals).

A normal baseline activated clotting time is 110

to 130 seconds. A low baseline should alert the

anesthesia provider to a hypercoagulable state.

Activated clotting times between 300 and 600 seconds are acceptable for cardiopulmonary bypass to

be initiated. There is a linear relationship between

the activated clotting time and the milligram per

kilogram heparin dose for any given patient.3

 Determining the adequacy of protamine reversal is

one area in which heparin-level tests may be more

useful. Although plotting the heparin dose against

the activated clotting time can be used to determine

the protamine-reversal dose, the difficulty arises

when the clotting time remains elevated after the

protamine has been given. The reasons for this can

be (1) continued excess heparin or (2) a derangement of the coagulation system. The usual clinical

response is to give an additional dose of protamine.

If the activated clotting time remains the same or

is elevated further, then a coagulopathy should be

suspected.

Physiological monitoring of the hematological

system in the first echelon of care will be very basic.

Accuracy in the evaluation of the nonmechanical

bleeding can be obtained with a whole-blood clotting time. Decreased clotting factors should be

suspected if whole blood does not clot within 15

minutes. Measurements of prothrombin, partial

prothrombin, and bleeding time should be available at the third or fourth echelons. The ability to

measure activated clotting time intraoperatively

would also be useful. This approach should be

considered when logisticians are determining which

monitoring devices to include for each unit that

provides complex care.

Cardiovascular System

Physical examination will remain a mainstay in

the evaluation of the casualty’s cardiovascular system. Assessment should include mental status examination, presence of nausea or vomiting, capillary refill, vital signs, coolness of extremities, and so

forth. Other, more-direct monitors of the cardiovascular system include methods to monitor blood

pressure and central venous pressure, and monitors of the heart for rhythm and ischemia.

Blood Pressure

Noninvasive Monitoring. Depending on the

equipment available, blood pressure can be monitored by several noninvasive methods:

• Doppler technique,

• oscillations of an aneroid manometer during deflation of a manual cuff,

• return of tactile pulses during deflation of a

manual cuff,

• auscultatory method using Korotkoff’s

sounds, and

• automated blood pressure devices.

Of these, the first three monitor only systolic pressures; the others, in addition, monitor diastolic and

mean pressures.

The simplest way to detect systolic blood pressure is to palpate the pulse while an occluding cuff

is deflating. A modification of this technique involves watching for oscillations of the aneroid manometer during deflation of the occluding cuff.

Once, the most common technique for indirect

manual measurement of blood pressure employed

by anesthesia care providers in hospitals in the continental United States was the auscultatory method of

using Korotkoff’s sounds.4 A stethoscope or an

automatic blood pressure–monitoring device placed

over an artery serves as a detector. Slightly more

sophisticated detectors include a Doppler or other

sound-amplifying device as a signal detector. By

placing the ultrasonic Doppler device over the radial artery, the anesthesia provider detects blood

flow by listening for the characteristic “swishing”

sounds. The Doppler method utilizes a 10-Hz ultrasonic device coupled to a transducer/receiver assembly. This device detects the difference in frequency between transmitted and reflected sound in

response to deflation of an occluding cuff. The Doppler signal is detected when blood flow causes movement of the arterial wall during systole. There is

good correlation between measurement of systolic

blood pressure via Doppler and direct arterial monitoring.5

 Ultrasonic gel (if available) will provide a

helpful medium for transmitting sound. The blood

pressure cuff on the patient’s arm is inflated as

above. As the cuff is slowly deflated, the point at

which sounds are again heard correspond to the systolic pressure. The Doppler device may be useful
Physiological Monitoring

107

tus, and have transduced pressure-monitoring capability (Figure 5-1). These new units can run on

alternating or direct current. They are compact,

weighing just a few pounds, and are currently used

in tertiary-care centers as transport monitors. In the

future, we are likely to find these units at third,

fourth, and higher echelons of combat casualty care.

Invasive Monitoring. The medical officer’s ability to evaluate a casualty’s arterial waveform is a

major advantage of direct monitoring of arterial

blood pressure in the trauma setting. The arterial

waveform allows a qualitative assessment of the

patient’s blood volume status to be made. The area

beneath the arterial waveform is affected by myocardial performance, systemic vascular resistance,

and circulatory volume status. The more common

sites of arterial cannulation are listed in Exhibit 5-1.

Most studies reporting the complications of direct

arterial cannulation involve the radial artery. Complications include decreased circulation, infection,

vasospasm, thrombosis, embolism, aneurysm formation, and hematomas.

The necessity of performing an Allen’s test before cannulation of the radial artery has been questioned.7 The incidence of thrombosis of the radial

artery relates to the size of the catheter used. One

study8 found a 34% incidence of thrombosis when a

18-gauge catheter was used, compared to an 8%

prevalence when a 20-gauge catheter was used. The

incidence of catheter thrombosis also increases with

the duration of cannulation. The safety of brachialEXHIBIT 5-1

SITES OF ARTERIAL CANNULATION

End Arteries

Brachial

Femoral

Other Arteries

Radial*

Ulnar*

Dorsalis pedis

Axillary

* Cannulation of both arteries of the same arm is not

recommended because of the risk of significant occlusion of blood flow to the hand.

Fig. 5-1. This patient monitor, the PROPAC 104 (portable

anesthesia circuit, manufactured by Protocol Systems, Inc.,

Beaverton, Ore.), has ports for noninvasive measurement of

arterial blood pressure, electrical activity of the heart, and

temperature, and has two additional pressure ports.

and should be considered as supplementary equipment for the intermediate and complex levels of care.

The automated oscillometric method for measuring blood pressure has become the most common

method used by anesthesia care providers for

noninvasive blood pressure monitoring. Its advantages over the techniques discussed above are its

greater accuracy and ability to measure mean blood

pressure. The devices manufactured currently employ an electric pump to generate the pressure required to inflate the occluding cuff. A microprocessor controls the cuff inflations and deflations. A

solenoid valve allows incremental deflation of the

cuff. The cuff also acts as the signal sensor that

responds to oscillations in the limb. A pressuresensing function is performed by a pressure transducer, and digital readout of the systolic, diastolic,

and mean blood pressure is provided. Under ideal

circumstances, the accuracy of these units compared with direct arterial measurements is usually

within 10 mm Hg.6 Problems in obtaining measurements occur when the patient moves, when there is

substantial beat-to-beat variability in the blood pressure (eg, atrial fibrillation), and with very slow

heart rates. Originally, automated oscillometric

units were somewhat bulky and required electricity

to operate. Newer units have backlit liquid crystal

displays. In addition to their ability to monitor

blood pressure noninvasively, many units currently

manufactured are also capable of monitoring pulse

oximetry and the heart’s electrocardiographic sta-
Anesthesia and Perioperative Care of the Combat Casualty

108

and femoral-artery cannulations is established; they

serve as other sites of direct arterial monitoring.9,10

The common way of measuring direct arterial

pressure is to connect the indwelling arterial catheter to a transducer that converts hydrostatic pressure into movement of a thin diaphragm. Ultimately, this energy is converted into an electrical

signal, which is amplified and converted to analog

or digital signals or both. Digital readouts and

analogue displays of waveforms can be viewed on

small monitors. A useful invasive means of measuring mean blood pressure is to use a manometer

connected to the arterial tubing (formerly connected

to a transducer) (Figure 5-2). This method provides

a means of monitoring the patient’s mean blood

pressure, which may be particularly useful during

transport or when transducers become unavailable

for whatever reason. This type of monitor has the

disadvantages of only giving an analog display of

the mean blood pressure. The arterial waveform

cannot be viewed.

Central Venous and Pulmonary Artery Pressures.

Central venous lines are used for several reasons,

including perioperative administration and management of fluids in the critically ill patient, administration of vasoactive drugs, and obtaining blood

samples. Central venous pressures can be monitored by using either pressure transducers or a

water manometer.

Normal central venous pressure is between 0 and

5 mm Hg or 0 and 7 cm H2O. Although it is unlikely,

it is possible that central venous pressure monitoring will be used at the third echelon of care. At this

level, saline-filled manometers may be used because pressure transducers will be in short supply.

The saline-filled manometers are measured in centimeters of water (1 mm Hg is equal to 1.36 cm H2O).

Measurements are made at the level of the right

atrium (the midaxillary line). This is considered the

zero point (the point at which the zero on the manometer is positioned). In fixed facilities, where

more-complex monitoring is available, central

venous pressure can be monitored using a pressure

transducer. This allows both an analog display of

the central venous waveform and a digital readout

of the pressures. One advantage of having the

waveform displayed is that the right ventricular

wave pattern can be differentiated from the right

atrial wave pattern. This would be particularly

useful in verifying correct location of the catheter tip.

The four most accessible sites available for the

insertion of central venous pressure–monitoring

lines are the internal or external jugular, subclavian, antecubital, and femoral veins. The right

internal jugular approach is the one most commonly used for central vein catheterization. This is

because it (a) provides a straight path to the right

atrium; (b) provides a clean site (the incidence of

thrombophlebitis is low); and, perhaps most importantly, it (c) is easily accessible to the anesthesia

provider during the operative procedure. The external jugular approach requires the use of a guide

wire with a J-tip to allow it to be maneuvered into

the central circulation.

Although the pulmonary artery catheter is used

in medical centers in the continental United States,

it has not yet been hardened (miniaturized and/or

made sufficiently sturdy) for battlefield use; therefore, this device is seen only infrequently at thirdechelon hospitals. Pulmonary artery catheters require that pressure transducers be used to confirm

placement. The same approaches that are used for

placement of a central venous pressure line can be

used for pulmonary artery catheter placement. The

insertion and management of this device require

experience with its use.

The uses of pulmonary artery catheters include

Fig. 5-2. A sphygmomanometer can be used as an ad hoc

field blood pressure monitor, but only the mean pressure

can be measured.
Physiological Monitoring

109

the following:

• hemodynamic monitoring of both central

venous pressure and pulmonary artery

pressures;

• monitoring of cardiac output via the

thermodilution technique;

• evaluation of changes in compliance of the

left ventricle and, thus, evaluation of myocardial ischemia;

• measurement of mixed venous saturation;

• central infusion of cardiotonic drugs; and

• insertion of intravenous pacing wires

through pacing ports added to the catheter.

The use of these catheters would most likely be

restricted to the complex level of care provided by

the evacuation hospital or specialized hospital ship.

Electrocardiography

The electrocardiograph is used for monitoring

heart rhythm and ischemia. Hospitals throughout

the United States use either three-lead or five-lead

systems. The standard limb leads in general use

monitor cardiac rhythm. Precordial leads are better

for evaluation of ischemia. It is possible that only a

three-lead system may be available in field hospitals. When using only three leads, the heart can still

be evaluated for rhythm and ischemia: place the

reference lead on the patient’s left shoulder and the

positive lead over the lateral precordial surface (V5

position). By switching between lead I and lead II

on the electrocardiograph, we can then view a limb

lead and a modified precordial lead (modified V5).

The capability to monitor the electrical activity of

the heart should be found at both the intermediate

and complex levels of care.

Transesophageal Echocardiography

At present, evaluation of the cardiovascular system

primarily involves hemodynamic monitoring. The

introduction of transesophageal echocardiography

has presented a new tool that provides useful information to the physician in highly sophisticated centers. The uses of transesophageal echocardiography

include both monitoring for air embolism and monitoring of cardiac function.

Echocardiography uses sound waves emitted by

sound transducers in a narrow beam. The sound

waves travel through tissues and are reflected. The

intensity of the reflected echoes is a function of the

density of the reflecting tissue. Sound waves emitted by an esophageal transducer have to pass

through only the esophageal wall and pericardium

before reaching the heart. Thus, there is less likelihood of image distortion. Other advantages of

transesophageal echocardiography include both the

stability of the position of the transducer and the

potential of continuous intraoperative recording.11

This monitor is very unlikely to be present during the operative care of the combat casualty. Currently, these monitors require excessive space and

specialized training for their use. Although

transesophageal echocardiography might provide

useful information in specific instances, it remains

a monitor that most likely will not be seen in hospitals that receive battlefield casualties.

Respiratory System

The respiratory system can be monitored by

physical exam (presence or absence of labored

breathing), stethoscopy, the casualty’s color (presence or absence of cyanosis), pulse oximetry, arterial blood gases, and various sophisticated monitors such as capnography or mass spectrometry.

Pulse Oximetry

The pulse oximeter continuously measures the

oxygen saturation of the arterial blood (SaO2, which

is expressed as a percentage). Of more importance,

however, is the oxygen content of the arterial blood

(CaO2, which is expressed as grams of oxygen per

100 mL of blood), which is defined as SaO2 multiplied by the oxygen capacity (1.36 mL of oxygen per

gram of hemoglobin [Hb]), multiplied by the concentration of Hb (grams per 100 mL of blood) divided by 100. The definition of Hb saturation (also

called oxyhemoglobin, O2Hb) does not include that

fraction of Hb that may be either methemoglobin

(MetHb) or carboxyhemoglobin (COHb). Therefore, the saturation percentage of Hb can be expressed as

% saturation (SaO2) = (CaO2 / total Hb content)

• 100

where total Hg is equal to O2Hb + Hb + COHb +

MetHb. Under normal circumstances, this correction is of little importance. However, in the casualty

who is suffering from smoke inhalation (with the

associated potential for carbon monoxide poisoning, in which 10%–20% of the total Hg content may

be in the form of COHb), use of the complete formula to estimate saturation becomes mandatory.

The oximeter estimates SaO2 by transilluminating
Anesthesia and Perioperative Care of the Combat Casualty

110

the ear or other appendage with light of two different wavelengths (one in the red range, the other in

the infrared). The transmitted light is then measured with a photodetector. The pulsatile component of the transmitted light is related to the absorbances of the SaO2. All pulse oximeters assume that

the only pulsatile absorbance between the light

source and the photodetector is due to arterial blood.

The baseline absorbance represents the light that is

absorbed by tissue, venous blood, or the capillary

bed. Thus, the oximeter is able to differentiate SaO2

from venous or tissue saturation. The pulse oximeter

further assumes that there are only two absorbing

Hb types in the blood (ie, O2Hb and Hb). If MetHb

or COHb or both are present, they contribute to the

pulse absorbance signal and, therefore, alter the

SaO2. Other limitations include any substance that

absorbs light at the red and infrared pulse oximeter

wavelengths used. Examples would be the use of

methylene blue, indigo carmine, and indocyanine

green dyes, which decrease the SaO2. Colored nail polish

also can adversely effect the measurement of SaO2.

Pulse oximetry is an extremely useful noninvasive

monitor of the respiratory system and has quickly

become a standard of practice in operating rooms

throughout the continental United States. Although

it provides much information, however, pulse

oximetry is not without pitfalls. Oxygen saturations greater than 90% indicate an arterial oxygen

tension (PaO2) greater than 60 torr. Patients who are

given supplemental oxygen can have a significant

shunt (causing decreases in PaO2) before alterations

in SaO2 are noted. For example, if a casualty with

lung contusions were placed on supplemental O2,

his initial arterial blood gas could show a PaO2 of

300 torr. Oxygen saturation would show 100%. The

casualty’s condition could worsen such that the

arterial blood gas might show a PaO2 of 100 torr and

the SaO2 would still be 99% to 100%. Thus, a significant decrease in PaO2 might not be noted by the

pulse oximeter. Another pitfall could occur in the

casualty who has been exposed to cyanide. In this

instance, SaO2 may remain high, despite the need

for high concentrations of oxygen and treatment of

cyanide toxicity.

The pulse oximeter may not be part of the standard equipment found at the second or third echelons of care, but it should be added as additional

equipment. It should also be considered in the

austere first-echelon setting when it is anticipated

that anesthesia will be provided if electricity and

space for equipment are available and maintenance

can be provided.

Arterial Blood Gases

The ability to measure arterial blood gases serves

as the standard in evaluating oxygenation. Modern

measurement devices depend on selectively permeable membranes and the electrochemical activity of the gases present; besides measuring oxygen

tension, modern electrodes also measure pH and

pCO2. The platinum electrode (Blood Gas System,

manufactured by CIBA Corning Diagnostics,

Medfield, Mass.) is used for measuring oxygen tension. The devices that monitor arterial blood gases

are small, precise, and very sturdy. Arterial blood

gas monitors will most likely be found at the more

complex level of care (general hospitals); they may

also be found at the intermediate level but certainly

not in the austere setting.

Equipment able to continuously monitor oxygen

tension is currently under development. The primary problem has been with miniaturization of the

electrode. Another technology uses fiberoptic sensors, which can be miniaturized more easily. A

continuous oxygen-tension monitor has recently

been approved for clinical use, and this technology

may soon be available for combat casualty care. At

present, however, oxygen tension is measured only

intermittently and only at the fourth echelon of

medical care and higher.

Capnography

The analysis of end-tidal carbon dioxide (ETCO2)

has only recently become commonplace in operating suites, but it has rapidly become a standard of

practice in many community hospitals. This type of

monitoring

• provides useful information regarding

mechanical and gas-exchange functions of

the patient’s lungs,

• detects changes in the patient’s metabolic

and cardiovascular function, and

• helps identify malfunctions of breathing

circuits that are used while patients are

under anesthesia.

The systems most commonly available use infrared

light absorption by carbon dioxide. The expired carbon dioxide absorbs light in proportion to its concentration. The sensors are placed in line with the

expired gases, and a continuous waveform provides the capnograph. This type of in-line system

for measuring ETCO2 is relatively fragile and the

equipment is bulky. Capnography can also use a gas-
Physiological Monitoring

111

withdrawal system (ie, mass spectrometry) as a way

of measuring ETCO2; however, this requires very sophisticated instrumentation. The gas-withdrawal

system to transport the gas to be measured to the

measuring device causes a delay in measurement of

the capnogram. Also, the moisture that develops

within the gas-transport tubing often will obstruct

the flow of the gases to the measuring device. ETCO2-

measuring devices are not likely to be seen except at

the more complex levels of combat casualty care.

Pulmonary Function

Lung compliance (the change in volume for a

given change in transpulmonary pressure) is another monitor for evaluating the respiratory system

in patients who require intubation, but we should

bear in mind that the word “lung” is something of

a misnomer: what is actually measured is the total

compliance of the pulmonary tissue and the chest

wall. Furthermore, two different compliances—

dynamic and static—can be measured, depending

on whether air is in motion when the measurements

are made. Most mechanical ventilators have a pressure gauge that can be used to determine airway

pressure on a moment-by-moment basis and, therefore, can be used to measure dynamic compliance.

Dynamic compliance (DC) for a patient on a ventilator is defined as tidal volume (TV) divided by the

peak airway pressure (PAP) minus the pressure at

end expiration (PEEP):

DC = TV / (PAP – PEEP)

Normal lung compliance is approximately 100

mL/cm H2O. A compliance of 25 mL/cm H2O) is

significantly decreased. Decreased dynamic compliance (increased peak airway pressure) may mean

an obstructed endotracheal tube, bronchospasm, or

a pneumothorax. Static compliance (SC) is calculated:

SC = TV / (plateau pressure – PEEP)

where plateau pressure is the pressure during the

period in which there is no airflow. This is commonly estimated during the period of inspiratory

pause. Decreased static compliance may signify

atelectasis or increased lung water. Static compliance is a useful monitor for casualties with adult

respiratory distress syndrome (ARDS).

Renal System

Monitoring the renal system serves as a means of

measuring not only renal function but also the

casualty’s intravascular volume status. Useful

monitors include urinary output, sodium concentration, and specific gravity. The patient should be

able to maintain a urinary output of at least 0.5 mL/

kg/h. Urinary specific gravity and sodium concentration help the medical officer determine whether

the kidneys are attempting to conserve water (an

indicator of the casualty’s volume status). In

nonhypovolemic patients who are not taking diuretics, urinary sodium concentration should be

higher than 20 mEq/L and specific gravity lower

than 1.020.

Above the second echelon of care, Foley catheters

will be the primary device for monitoring renal

function. Laboratory methods capable of measuring

blood urea nitrogen or creatinine or urinary sodium

concentration are not likely to be found at other

than fourth-echelon medical treatment facilities.

Nervous System

Monitoring the nervous system involves both

physical examination and the use of sophisticated

equipment. Due to equipment limitations of durability and size, anesthesia care providers currently

have limited ability to monitor the nervous system.

Central Nervous System

Monitoring the central nervous system is discussed in detail in Chapter 16, Neurological Injuries. The equipment used in this monitoring is often

highly sensitive, fragile, and bulky; it is found only

at the highest echelons of care. However, as technology improves and miniaturization of equipment

then becomes practicable, these monitors will likely

be used in the field.

Intracranial Pressure. For the most part, monitoring of the central nervous system will consist of

mental-status checks and the physical examination.

Intracranial pressure can be monitored at the fourth

echelon of care and higher: specialized equipment

is required and the monitors are generally inserted

by neurosurgeons. The normal value for intracranial pressure is less than 10 cm H2O.

Devices for monitoring intracranial pressure can

be classified according to (a) the anatomical location at which the device is placed and (b) the method

by which intracranial pressure is measured. Anatomically, these monitors can be placed in the lumbar spine, cervical spine, posterior fossa, or supratentorial area of the cranium. The supratentorial

area is the preferred location for placement of the
Anesthesia and Perioperative Care of the Combat Casualty

112

monitor, because insertion of a catheter into the

subarachnoid space below the tentorium cerebri

can cause a potentially fatal decrease in pressure

there and subsequent herniation of the uncus of the

temporal lobe or the cerebellar tonsils.

Devices in current use can be fluid-coupled (ie,

the pressure-monitoring device is connected to a

transducer by a column of fluid). The transducer

should be at the level of the external auditory meatus while the intracranial pressure is being measured. Routine pressure tubing and transducers

used for arterial and central venous pressure monitoring are not used to monitor intracranial pressure.

The flow through the standard tubing (approximately 2 mL/h) could harm a patient with increased

intracranial pressure. Flushing the monitor tubing

would also be harmful. Care must be taken not to

inject any fluid into this system. Newer devices

now use fiberoptics instead of a fluid-coupled system to transmit pressure waves to the pressuremeasuring device.

The intraventricular catheter is a simple device

used for measuring intracranial pressure. It can be

used both as a monitor and as part of a therapeutic

regimen. The device is coupled directly to the

cerebrospinal fluid and the transducer. In the event

of increased intracranial pressure, fluid can be drawn

off as needed. Iatrogenic infection can be introduced because this technique requires that the catheter be inserted through brain tissue; the incidence

of such infection is estimated to be less than 6.3%.12

Other devices used to monitor intracranial pressure

include the subarachnoid bolt and epidural devices. These devices allow for monitoring without

invading brain tissue.

Encephalography. The conventional, multichannel electroencephalograph is the standard against

which all other types of monitors of the electrical

activity of the brain are compared. The electroencephalograph and its electrodes are large and

cumbersome. In addition, conditions within the

operating room make it a hostile environment for

electroencephalography (eg, electrocautery interference). The difficulty in using the conventional,

multichannel electroencephalograph is largely

overcome by monitoring a processed electroencephalogram (eg, the cerebral function monitor, which is

a single-channel processed electroencephalogram).

The use of the cerebral function monitor during

carotid endarterectomy,13 deliberate hypotension,14

and cardiopulmonary bypass15 is well documented.

However, the inability to examine the behavior of

different frequencies within the electroencephalograph is a major drawback. The Lifescan Monitor

(manufactured by Neurometrics Inc., San Diego,

Calif.) displays a processed electroencephalogram

in which brain waves can be viewed as three-dimensional vertical spikes. The height of the spike

represents the amplitude of the wave, its horizontal

position represents its frequency, and time is represented on the Z axis. This device also can monitor

sensory evoked potentials. The processed electroencephalogram is useful in monitoring cerebral

ischemia and the effects of anesthetic drugs.16–18

There are many types of electroencephalographs

that have differing processing techniques. Clinically, all the processing techniques show frequency

changes when the raw electroencephalogram slows,

and amplitude changes when it flattens. The difficulty lies in comparing two differing processing

techniques. Qualitatively, the processed electroencephalogram may be quite useful. However, this

monitor is unlikely to be seen at any echelon of care

except in hospitals within the continental United

States.

Sensory Evoked Potentials. The intraoperative

use of sensory evoked potentials is labor intensive.

Because many anesthesia care providers lack the

time or skill to monitor and interpret sensory evoked

potentials, their use has often been limited to large

medical centers where neurologists or electrophysiologists are available. Some facilities have a specialized technician who assists in the technical aspects of the monitoring.

Sensory evoked potentials have been used in

neurosurgery,19,20 orthopedic spinal surgery,21 and

during positioning of the patient where brachial

plexus injuries may occur.22 Its usefulness as a

monitor during care of combat casualties is doubtful, because even the most basic machines are so

labor intensive and bulky. This monitor will most

likely be found only at the larger medical centers in

the continental United States.

Peripheral Nerve Stimulators

Peripheral nerve–stimulator devices allow muscle

relaxation to be monitored while potent muscle

relaxants are administered. They can also be useful

when regional anesthesia is performed using a

nerve-stimulation technique (see Chapter 11, Neuromuscular Blocking Agents, Figure 11-2). Those

who select the nerve stimulator that will be used at

the third and fourth echelons of care should take

this dual use into consideration. A nerve stimulator

with the ability to adjust the amount of output in

milliamps (0–10.0 mA and 0–100 mA) will be more

versatile. The ability to identify nerve structures by
Physiological Monitoring

113

direct stimulation of nerves or muscles or both

during the surgical procedure would be an additional benefit to the surgeon.

Temperature

The ability to monitor temperature will no doubt

be found at both the third and fourth echelons of

care. Thermocoupled liquid crystal display devices

that paste onto the skin will have little value in the

field. Nondisposable devices that allow temperature monitoring at various sites will be most helpful. Monitoring core body temperature—via esophageal or rectal temperature probes—will provide

the most useful information regarding the casualty’s

temperature.

COMPUTERS IN ANESTHESIA

In anesthesia, computers can be used as microprocessor-based drug and anesthesia delivery systems or as a means of patient-data management.

Currently, there are no well-established systems in

which physiological data are processed by computer and which subsequently permit the delivery

of anesthesia drugs to be modified based on the

data received by the microprocessor. More commonly, computers receive physiological data and

record it on the anesthesia record. The ability to

detect detrimental changes in the casualty’s status

and trigger the appropriate alarms are what separates simple data collection from computerized

monitoring. Improvements in the technology of

artificial intelligence will be required before useful

microprocessor-based anesthesia drug delivery systems are seen either outside the research area or on

the battlefield. The computers required for such

elaborate tasks require processing in parallel with

data received from monitors measuring cardiovascular, respiratory, and other physiological parameters. The enormous amount of data will

then require processing so that appropriate responses (mimicking those of a human expert) will

be made.

Computerized data recording is a much more

manageable task. The objective is to make record

keeping easy and complete: to free the anesthesia

provider to monitor the casualty, not to institute

time-consuming tasks. Accurate, detailed records

of data from various physiological monitors can be

stored and printed. The medical officer’s ability to

distinguish between artifact and real data, and a

user-friendly computer program’s processing of

human input are essential to the practicability of

any computerized record system.

SUMMARY

Monitoring of the combat casualty can be both

adequate and austere. Levels of care practiced in

fixed medical facilities such as combat support or

general hospitals differ from those practiced closer

to the battlefield. Strategies for obtaining data from

various physiological systems for use in management of the medical care of the combat casualty

need to be decided in advance, as do the types of

monitors that can be expected at each echelon of care.

As technological advances make sophisticated

equipment smaller, simpler, and sturdier for transport, the kinds of monitoring devices that are available at each echelon will undoubtedly change, making more-sophisticated monitoring available closer

to the battlefront. The pulse oximeter is one example; capnography will most likely follow.

1. Harken LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function and perioperative

blood loss. N Engl J Med. 1972;287:155–159.

2. Rosenberg RD. Actions and interactions of antithrombin and heparin. N Engl J Med. 1975;292:146–151.

3. Bull BS, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation, II: The use of a dose-response

curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975;69:685–689.

4. Korotkoff N. On the subject of methods of determining blood pressure. Bull Imperial Med Acad. 1905;1:365.

5. Stegall HF, Kardon MB, Kemmerer WT. Indirect measurement of arterial blood pressure by Doppler ultrasonic

sphygmomanometry. J Appl Physiol. 1968;25:793–798.

REFERENCES
Anesthesia and Perioperative Care of the Combat Casualty

114

6. Ramsey MI. Noninvasive automatic determination of mean arterial pressure. Med Biol Eng Comput. 1979;17:11–18.

7. Slogoff S, Keats AS, Arlund C. On the safety of radial artery cannulation. Anesthesiology. 1983;59:42–47.

8. Bedford RF. Radial arterial function following percutaneous cannulation with 18- and 20-gauge catheters.

Anesthesiology. 1977;47:37–39.

9. Barnes RW, Foster EJ, Janssen GA, Boutros AR. Safety of brachial arterial catheters as monitors in the intensive care

unit: Prospective evaluation with Doppler ultrasonic velocity detector. Anesthesiology. 1976;44:260–264.

10. Glenski JA, Beynen FM, Brady J. A prospective evaluation of femoral artery monitoring in pediatric patients.

Anesthesiology. 1987;66:227–229.

11. Thys DM, Konstadt S, Hillel Z. Intraoperative echocardiography. In: Lake C, ed. Clinical Monitoring. Philadelphia,

Pa: WB Saunders; 1990: 197–235.

12. Rosner JJ, Becker DP. ICP monitoring: Complications and associated factors. Clin Neurosurg. 1976;23:494–519.

13. Cucchiara RF, Sharbrough FW, Messick JM, Tinker JH. An electroencephalographic filter-processor as an indicator

of cerebral ischemia during carotid endarterectomy. Anesthesiology. 1979;51:77–5179.

14. Patel H. Experience with the cerebral function monitor during deliberate hypotension. Br J Anaesth. 1981;53:639–

644.

15. Kritikou PE, Branthwaite MA. Significant changes in cerebral electrical activity at onset of cardiopulmonary

bypass. Thorax. 1977;32:534–538.

16. Spackman TN, Faust RJ, Cucchiara RF, Sharbrough FW. The comparison of the Lifescan EEG monitor with EEG

and cerebral blood flow for detection of cerebral ischemia. Anesthesiology. 1985;63:A187. Abstract.

17. Smith NT, Demetrescu M. The EEG during high-dose fentanyl anesthesia. Anesthesiology. 1980;53:S7.

18. Demetrescu M, Kavan E, Smith NT. Monitoring the brain condition by advanced EEG. Anesthesiology. 1981;53:A130.

Abstract.

19. Grundy BL, Lina A, Porocopio PT, Jannetta PJ. Reversible evoked potential changes with retraction of the eighth

cranial nerve. Anesth Analg. 1981;60:835–838.

20. Symon L, Wang AD, Costa e Silva IE, Gentili F. Perioperative use of somatosensory evoked potentials in aneurysm

surgery. J Neurosurg. 1984;70:269–275.

21. McPherson RW, North RB, Udvarhelyi GB, Rosenbaum AE. Migrating disc complicating spinal decompression in

an achondroplastic dwarf: Intraoperative demonstration of spinal cord compression by somatosensory evoked

potentials. Anesthesiology. 1984;61:764–767.

22. Mahla M, Long DM, McKennett J, Green C, McPherson R. Detection of brachial plexus dysfunction by somatosensory evoked potential monitoring—A report of two cases. Anesthesiology. 1984;60:248–252.
115

Deployable Hospitals

Chapter 6

DEPLOYABLE HOSPITALS

WILLIAM JAMES PHILLIPS, M.D.*; MARC A. PARADIS, M.D.†; AND RONALD F. BELLAMY, M.D.‡

INTRODUCTION

HISTORY OF DEPLOYABLE MEDICAL SYSTEMS

DEPLOYABLE ANESTHESIA EQUIPMENT

Physiological Monitors

Resuscitative Equipment

Medical Gases

Blood-Recovery Equipment

Anesthetic Drugs

Miscellaneous Equipment

Fluid Resuscitation

DEPLOYABLE MEDICAL SYSTEMS–EQUIPPED HOSPITALS

Patient Care Areas

Ancillary Support Areas

DEPLOYABLE HOSPITALS IN THE PERSIAN GULF WAR

MEDICAL FORCE 2000

Mobile Army Surgical Hospital

Forward Surgical Team

Combat Support, Field, and General Hospitals

MEDICAL REENGINEERING INITIATIVE

HOSPITAL SHIPS

SUMMARY

*Major, Medical Corps, U.S. Army Reserve; formerly, Anesthesiologist, 528th Special Operations Support Battalion (Airborne), U.S. Army

Special Operations Command, Fort Bragg; Staff Anesthesiologist, Womack Army Medical Center, Fort Bragg, North Carolina 28307; currently,

Staff Anesthesiologist, Mayo Clinic, Rochester, Minnesota

†Formerly, Lieutenant Colonel, Medical Corps, U.S. Army; Staff Anesthesiologist, Walter Reed Army Medical Center, Washington, D. C.

20307-5001; currently, Chief, Cardiac Anesthesiology Section, Hartford Hospital, Hartford, Connecticut 06106

‡Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

116

INTRODUCTION

No modern general will go into battle without

taking with him at least a rudimentary hospital

system. When the tempo of warfare was governed

by the speed of marching men and horses, existing

deployable hospitals were usually able to keep pace

with combat units. The primitive nature of medicine and surgery minimized the logistical and transportation needs of such hospitals, which were frequently nothing more than tents with cots. The

imperatives of modern medicine and surgery, together with the advent of mechanized warfare, have

vastly increased the challenge of providing medical

support—especially surgical care for combat casualties. The problems implicit in designing mobile

hospitals were not especially apparent during the

positional warfare that characterized much of World

War I, but they became obvious during World War

II. Medical commanders soon recognized that unless hospitals capable of providing surgical care for

combat casualties were able to accompany rapidly

moving armored units, casualties would necessarily be subjected to a lengthy evacuation. For many,

this was incompatible with survival. Furthermore,

the lifesaving potential of modern surgery could be

realized only if operations were carried out shortly

after wounding had occurred. To wait for the combat casualty to reach a communications zone hospital, as was done in World War I, was to minimize the

value of modern surgery.

The need for hospitals that had the tactical mobility of combat units became apparent to the U.S.

Army during the campaigns in North Africa and

Italy in 1943. It was recognized that a small fraction

of those wounded in action (perhaps 10%) were

“nontransportable”: they could not survive evacuation from the battlefield to the corps-level hospitals. The major achievement of military surgery by

the U.S. Army in World War II was forward surgical

care for such casualties. Small ad hoc surgical

hospitals (30–60 beds) were created and attached to,

and could move with, division-level medical units.

The basic hospital module was a platoon-sized unit,

three of which constituted an existing Table of Organization and Equipment (TOE) unit: the field

hospital. Teams of surgeons and anesthesia providers were attached to the field hospital platoons from

army level medical replacement units known as

auxiliary surgery groups. Mobility for the combined surgical team–field hospital platoon was provided by its own organic (ie, intrinsic; included in

Fig. 6-1. The mobility and simplicity of World War II–

vintage surgical teams are apparent in this photograph

taken in Italy in 1944. Several jeeps with trailers and a

small truck were found to be sufficient to transport the

surgical personnel and specialty equipment. Tents, cots,

and other equipment were provided by the unit being

supported. Note that several members are watching

the sky, possibly for enemy aircraft. Their actions emphasize how far forward surgical teams were deployed.

Reprinted from Brewer LA III, Burford TH. Administrative considerations in the Mediterranean (formerly

North African) Theater of Operations. In: Berry FB, ed.

Thoracic Surgery. Vol 1. In: Coates JB Jr, ed. Surgery in

World War II. Washington, DC: US Department of the

Army, Medical Department, Office of The Surgeon General; 1963: 88.

the TOE) vehicles (Figure 6-1). Simplicity to the

point of austerity was their dominant feature; for

example, operating rooms were tents or buildings

of convenience (Figures 6-2 and 6-3). The equipment believed to be essential by World War II surgical teams is listed in Exhibit 6-1. The field hospital

platoon supplied the tentage, cots, and ancillary

equipment for the casualties, while logistical and

administrative support was provided by the supported division.

Only casualties who were considered to be likely

to die or to develop life-threatening complications

during evacuation to a corps-level evacuation hospital were treated by the surgical team–field hospital platoon. In general, the following categories

were treated in forward surgical hospitals1:
117

Deployable Hospitals

Fig. 6-3. A World War II surgical team performing an

operation. The notable austerity is in marked contrast to

what is found in today’s DEPMEDS (Department of

Defense’s Deployable Medical Systems)-equipped hospitals. Yet all the components required to perform lifesaving surgery are present. Reprinted from Odom CB.

Third US Army. In: Carter BN, ed. Activities of Surgical

Consultants. Vol 1. In: Coates JB Jr. Surgery in World War

II. Washington DC: US Department of the Army, Medical

Department, Office of The Surgeon General; 1962: 309.

EXHIBIT 6-1

ESSENTIAL EQUIPMENT FOR WORLD WAR II SURGICAL TEAMS

1. Adequate transportation assigned permanently to the team

2. Adequate lighting: at least 200 W candlepower for each operating table

3. A portable oxygen apparatus, with a large-cylinder reducing valve

4. A simple transfusion set for giving whole blood with citrate as the anticoagulant

5. A large autoclave for sterilizing towels, gowns, and sheets

6. Two covered metal sterilizers for boiling instruments

7. Two stoves for sterilizing

8. Three large, 30-gal galvanized cans for washing, waste, and soaking dirty and bloody linen

9. Linen, including 200 towels, 20 gowns, and 40 sheets; drapes for the surgical tents to keep out dirt and dust

10. A positive-pressure anesthesia machine and a portable suction apparatus

11. Basic surgical instruments as well as specialty instruments needed for such operations as a

thoracotomy

12. A walled or pyramidal tent to furnish living quarters for the surgical team

Adapted from: Brewer LA III, Burford TH. Administrative considerations in the Mediterranean (formerly North African)

Theater of Operations. In: Berry FB, ed. Thoracic Surgery. Vol 1. In: Coates JB Jr, ed. Surgery in World War II. Washington, DC:

US Department of the Army, Medical Department, Office of The Surgeon General; 1963: 88–89.

Fig. 6-2. A forward surgical unit set up somewhere in

France in 1944. Several tents house the operating room,

the shock or resuscitation ward, and the postoperative/

recovery ward. Environmental control was obviously

not optimal by today’s standards, nor was there much

protection against enemy action. Reprinted from Odom

CB. Third US Army. In: Carter BN, ed. Activities of Surgical Consultants. Vol 1. In: Coates JB Jr. Surgery in World

War II. Washington DC: US Department of the Army,

Medical Department, Office of The Surgeon General;

1962: 305.
Anesthesia and Perioperative Care of the Combat Casualty

118

• casualties with multiple wounds, who remained in shock despite intensive therapy;

• casualties with abdominal wounds, particularly those with possible concealed

hemorrhage;

• casualties with large, sucking chest wounds

or massive intrathoracic hemorrhage;

• casualties with thoracoabdominal wounds;

and

• casualties with wounds about the face and

neck that caused mechanical interference

with respiration.

Most casualties—those with orthopedic, softtissue, and head injuries—were sent to evacuation

hospitals in the rear after being given initial care by

the division-level medical unit with which the

surgical hospital was collocated. The decision as to

whether a casualty would be sent to the forward

surgical hospital was made by the triage officer of

the host division-level medical unit. The latter unit

was also responsible for evacuation of treated casualties. Strangely enough, although professional

relationships were clearly defined, formal command-and-control relationships among the three

units—the surgical team (army level), the fieldhospital platoon (corps level), and the supported

division—were ill defined. In all, about 100,000

operations were performed in the European theater by auxiliary surgery group surgical teams.

Probably one half were carried out in forward

surgical hospitals, of which there may have been

several hundred.2

Given the great success of the surgical team–

field hospital approach to providing forward surgical care, it is not surprising that after World War

II, it was decided to develop a formal TOE surgical

hospital. From this decision came the famous

mobile army surgical hospital (MASH) of the Korean War. Ironically, the conditions that gave rise

to the forward surgical hospital during World War

II were absent in Korea: after the first 9 months, a

static battlefield reminiscent of World War I had

developed. The MASHs remained immobile and,

in fact, became functionally identical to other hospitals (ie, they no longer were dedicated to the

treatment of only the most severely wounded casualties).

The MASH concept underwent considerable refinement during the period between the end of the

Korean War in 1953 and the United States’ intervention in Vietnam in the 1960s. One obvious

defect in the MASH and its World War II predecessor was that the use of canvas tents precluded

environmental control: a clean operating room was

not possible. Furthermore, not only was there a

potential for pollution from the environment but the

tents offered no protection against chemical and

biological warfare agents. To correct this, an advanced-technology approach was undertaken, with

the goal of creating an environmentally controlled

hospital with both strategic and tactical mobility. By

1963, this program had led to the development of the

medical unit, self-contained, transportable (MUST)

hospital.

The MUST hospital consisted of hard-walled, expandable shelters for certain parts of the facility (eg,

the operating room), and inflatable shelters for other

areas (eg, patient wards) (Figure 6-4). The facility

was transportable using special transporter vehicles;

electricity, air conditioning, and water were supplied via utility packs. The utility packs were large

units powered by a gas turbine that burned jet engine fuel (JP4), and they provided heating and cooling to all the inflatable and hard-walled shelters

(Figure 6-5). The utility packs worked well but

consumed large amounts of fuel. In 1966, the first

MUST hospital was deployed to Vietnam. Four

more were deployed before the war ended.

In retrospect, the MUST cannot be judged a success. Part of the reason for its relative failure arose

from the nature of the Vietnam War. Small U.S.

Fig. 6-4. An inflatable shelter in use in Vietnam, 1967. The

MUST (medical unit, self-contained, transportable) surgical hospital used two characteristic structures: hardwalled, expandable shelters that contained the operating

rooms and supporting services; and inflatable shelters

that served as patient wards. Although representing an

advanced-technology approach to providing a deployable

surgical facility, inflatable shelters were probably not

worth the effort. Setting them up was not easy and the

equipment required to keep them inflated was laborintensive. The inflatable shelters were also notably sensitive to battle damage.
119

Deployable Hospitals

Fig. 6-5. The mechanical equipment used to operate a

MUST (medical unit, self-contained, transportable) hospital consisted of a gas turbine, a generator, and an aircooling unit, which together constituted a utility pack.

Large tubes acted as conduits to provide cooled or heated

air to the treatment areas.

Army units deployed from base camps into the

surrounding enemy-held territory. By World War

II standards, distances in Vietnam were small, control of the air complete, and the number of casualties slight. It was, therefore, much more reasonable

to fly casualties into hospitals established in the

base camps than to move the hospitals with the

combat units. Given the nature of the Vietnam War,

MUST hospitals were never used the way they were

envisioned: as mobile hospitals to provide resuscitative surgery only to the most seriously injured.

Thus, MUST hospitals became immobile and increasingly lost their primary function. For example,

it was not unusual for the prototype MUST—the

45th Surgical Hospital—to function as a station

hospital and hold daily sick call for other units

assigned to the Tay Ninh base camp.

The major deficiencies of the MUST facilities

were as follows:

• They were not as adaptable to changing

mission requirements nor as deployable as

originally intended.

• The inflatable shelters were easily damaged

by enemy action and difficult to maintain.

• Fuel consumption and the cost of supplying power to the utility packs were unacceptably high.

• MUST-equipped hospitals lacked commonality among the army, navy, and air force.

Consequently, the U.S. Congress ended the MUST

program in 1979, and mandated in 1981 that all

future North Atlantic Treaty Organization (NATO)

third- and fourth-echelon hospitals would be standardized among the military services. This standardization program led to what is now known as

the Department of Defense’s Deployable Medical

Systems (DEPMEDS).

HISTORY OF DEPLOYABLE MEDICAL SYSTEMS

In June 1982, the Department of Defense established the Military Field Medical Systems Standardization Steering Group, which consisted of

general and flag officers of the U.S. Army, Navy,

Air Force, and Marine Corps, and was responsible

for directing the development of DEPMEDS.3 Their

mission was to standardize DEPMEDS to the degree

that would still allow the four services to accomplish

their distinct missions. DEPMEDS would (a) improve on the MUST’s modular design and reassembly and (b) be more flexible and easier to deploy. To

this end, the Military Field Medical Systems Standardization Steering Group established that

DEPMEDS equipment sets be adequate, affordable,

austere, maintainable, modular, transportable, usable in multiple service-specific configurations, usable by all four services, and suitable for transportation by strategic airlift. Other requirements came

from the Health Service Support Tenets, which stress

(a) providing healthcare as far forward as possible

and (b) maximizing the number of soldiers who

return to duty. DEPMEDS was designed for use

only in the third and fourth echelons of medical care.

The most important task for the Military Field

Medical Systems Standardization Steering Group

was to select medical and nonmedical equipment

and supplies that were not only acceptable to all

four services but would also adhere to their individual requirements. To do this, the steering group

convened 21 panels of medical experts from all four

services. The panels selected the medical equipment after reviewing and studying the Combat Zone

Assessment and Requirements (CZAR) model.

The original DEPMEDS database contained 316

patient conditions, which encompassed most of the

workload expected to be seen if war were to occur in

the NATO theater of combat. These 316 patient

conditions were accompanied by brief descriptions

of the conditions and their treatment. The treatment briefs, developed in late 1985, summarized

the procedures recommended for each hypothetical

patient. Because each hypothetical patient repre-
Anesthesia and Perioperative Care of the Combat Casualty

120

EXHIBIT 6-2

SELECTED DEPMEDS TREATMENT BRIEFS AND DEFINITIONS OF PATIENT CONDITIONS

Exhibit 6-2 continues

No. Injury Description Degree of Severity

1. Cerebral concussion Closed, with or without nondepressed Severe; loss of consciousness 2–12 h

linear skull fracture

3. Cerebral contusion Closed, with or without nondepressed Severe; loss of consciousness > 24 h, with

linear skull fracture focal neurological deficit

4. Cerebral contusion Closed, with or without nondepressed Moderate; loss of consciousness 12–24 h,

linear skull fracture without focal neurological deficit

5. Cerebral contusion Closed, with intracranial hematoma, with Severe; large hematoma (including

or without nondepressed linear skull hematoma) with rapidly deteriorating,

fracture comatose patient

7. Cerebral contusion Closed, with depressed skull fracture Severe; with associated intracerebral

hematoma and/or massive depression

9. Cerebral contusion Open skull fracture Severe; with intracranial fragments and/or

depressed skull fracture

10. Cerebral contusion Open skull fracture Moderate; without intracranial fragments

and/or depressed skull fracture

45. Wound: upper arm Open, penetrating, lacerated, without Severe

fracture, with nerve and/or vascular

injury

46. Wound: upper arm Open, penetrating, lacerated, without Moderate

fracture, without nerve or vascular

injury

47. Wound: upper arm Open, with fractures and nerve and Arm not salvageable

vascular injury

48. Wound: upper arm Open with fractures and nerve injury, Arm salvageable

without vascular injury

83. Injury: lung Closed (blast, crush) with pneumo- Severe, one lung with pulmonary contusion

hemothorax and acute, severe respiratory distress

85. Wound: thorax (anterior Open, superficial, lacerated, contused, Requires major debridement

or posterior) abraded, avulsed

87. Wound: thorax (anterior Open, penetrating, with associated rib Acute, severe respiratory distress

or posterior) fractures and pneumohemothorax

94. Thermal burn: trunk > 20% but < 30% of TBSA Full thickness

95. Thermal burn: trunk > 10% but < 20% of TBSA Full thickness

96. Wound: abdominal wall Lacerated, abraded, contused, avulsed Severe, requiring major debridement

(anterior or posterior) without entering the abdominal cavity

130. Wound: lower leg Open, lacerated, penetrating, perforating, Limb not salvageable

with fracture and nerve/vascular injury

131. Wound: lower leg Open, lacerated, penetrating, perforating, Limb salvageable

with fracture and nerve/vascular damage

134. Wound: ankle, foot, toes Open, lacerated, contused, without Requiring major debridement

fractures

135. Wound: ankle, foot, toes Open, lacerated, contused, without Not requiring major debridement

fractures

136. Wound: ankle, foot, toes Open, penetrating, perforating, with Limb not salvageable

fractures and nerve/vascular injury

Adapted from Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs.

Fort Detrick, Frederick, Md: 1990: E-1, E-2, E-4.
121

Deployable Hospitals

EXHIBIT 6-2: PATIENT CONDITIONS (continued)

PATIENT CONDITION 9:

CEREBRAL CONTUSION WITH OPEN SKULL FRACTURE, SEVERE—WITH

INTRACRANIAL FRAGMENTS OR DEPRESSED SKULL FRACTURE OR BOTH

LENGTH-OF-STAY MATRIX BLOOD USAGE

Echelon

3 4 5 Total Days Blood Hemorrhage Class

ICU 3 3 7 13 Echelon 3 2 II

ICW 0 5 143 148 Echelon 4 0

MCW 0 0 0 0

Total days 3 8 150 161

NATO Echelon 2

Assumptions: Litter, unconscious; moderate neuro deficits; responds to painful stimuli only; vital signs—moderate

tachycardia; rapid shallow resp; some require assisted ventilation; blood pressure normal; minimal-to-moderate hemorrhage; 4% die at this echelon.

Treatment: Stabilize head and C-spine; start IV; intubate 80%; dress and bandage open head wound. Transport on

litter, head-up 15°–30° position.

NATO Echelon 3

Assumptions: Litter; neuro status unchanged; Class II hemorrhage; vital signs same as Echelon 2; X ray shows

depressed skull fracture with intracranial frag; requires craniotomy; (50% died in hospital).

Treatment: Emergency Medical Treatment area: Place endotracheal tube in 20%; assist ventilation 100%; cardiac

monitor in 100%; IV to keep open 1 L Ringer’s lactate; inspect and dress head wound; nasogastric tube; Foley cath;

neurosurg meds; antibiotics; protect neck; X ray: skull, cervical spine; 100% portable chest; Lab: complete blood count,

electrolytes, type and crossmatch 3 units

Operating Room: 100% have craniotomies; central venous pressure monitor; 2 units blood; endotracheal

tube; antibiotics; 2 L Ringer’s lactate; operating room table time 150 min.

Wards: Intensive Care Unit: hyperventilate via endotracheal tube with 40% O2; Ringer’s lactate 3 L 1st

day; change head dressing; insert tube feeding; abdomen X ray; 100% tube feeding 2nd day; steroids; Foley; IV to keep

open after tube feeding begun; may require mannitol; IV antibiotic; cardiac monitor while on ventilator, possible 5%

cardiac arrest; complete blood count, electrolytes every other day; transcutaneous O2 for 3 days. Remove central venous

pressure monitor on day 3.

NATO Echelon 4

Assumptions: Litter; 50% conscious/50% unchanged; all require assisted ventilation x 2 days; all on tube feeding;

vital signs stable.

Treatment: Emergency Medical Treatment area: Check vitals, check IV, suction: ventilate; transport to ward;

complete blood count and electrolytes in emergency treatment area on 20%.

Operating Room: 100% have tracheostomies (30 min); operating room table time 60 min.

Wards: Intensive Care Unit: control ventilation with tracheostomy; continue IV; continue tube feeding;

continue monitoring; continue antibiotics; steroids; disconnect ventilator at day 2; complete blood count & electrolytes

every other day; continue Foley; transcutaneous O2 monitor 2 day; Intermediate Care Ward: vital signs; heparin lock to

continue IV antibiotics and steroids; tube feeding to continental United States; continue Foley to continental United

States; parenteral pain meds; prepare to transfer to Veterans Administration hospital Echelon 5.*

Ancillary Support: occupational therapy/physical therapy evaluation.

*Echelon 5 hospitals are within the continental United States, not in the theater

Reprinted from Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs.

Defense Medical Standardization Board, Fort Detrick, Frederick, Md: 1990: Rev 7/90.
Anesthesia and Perioperative Care of the Combat Casualty

122

sents the average in the spectrum of a particular

injury or disease, each treatment brief described (a)

the average amount of time and equipment needed

and (b) the average number of personnel and procedures required to treat a given injury.

The lists of equipment the panel had selected

were reviewed by a group of senior physicians

representing each service—the Joint Services Clinical Review Group—which, along with Logistics,

Dental, Nursing, and Pharmacy Quad-Service Review Groups, continues to review DEPMEDS equipment and supplies to ensure that the items are

reliable, compatible, complete, and ready to use.

There have been numerous annual revisions; major

changes were made in 1987 and 1990, and a major

update and revision occurred in March 1992.

Once the Joint Services Clinical Review Group

review was completed, the Medical Assemblage

Design Branch of the Academy of Health Sciences,

Fort Sam Houston, San Antonio, Texas, organized

the items into functional modules known as medical material sets (MMSs). It is these sets that allow

the armed services to deploy medical facilities with

markedly different capabilities and still maintain

the mandate for standardization. Three types of

sets were created4(p8):

• the basic MMS, which contains all the equipment, durable goods and a 3-day supply of

consumable equipment for a specific module in the hospital (eg, the Operating Room

MMS D301);

• the special-module MMS, which contains

equipment for additional capability (eg, the

Orthopedic Cast Clinic MMS D314); and

• the resupply MMS, which contains expendable and some durable goods, and can be

configured as needed for each individual

hospital.

In June 1984, the standardization mission of the

Military Field Medical Systems Standardization

Steering Group was given to the Defense Medical

Material Board, which was renamed the Defense

Medical Standardization Board. The Defense Medical Standardization Board continues to direct the

development of DEPMEDS and to standardize all

medical equipment to the extent consistent with the

missions of the individual military services.

The DEPMEDS MMSs were initially tested in

November 1984 at Fort Hood, Texas. In November

1985, the DEPMEDS database was again reviewed

by a quad-service panel of medical experts. Based

on the panel’s review, final changes to the MMSs

were made, and in March 1987, the Assistant Secretary of Defense for Health Affairs approved the sets

as the Department of Defense DEPMEDS sets.

DEPMEDS was further evaluated and tested by the

U.S. Navy during Operation Safe Haven (1987), the

U.S. Army with Joint Task Force Bravo in Honduras

during the 1980s, and the U.S. Air Force during

REFORGER exercises (1984–1988). Changes based

on these experiences resulted in the 1990 version of

DEPMEDS, which was more streamlined and fully

capable of meeting the quad-service field medical

requirements. Based on the experience gained from

the Persian Gulf War, DEPMEDS was again updated in March 1992.

The Defense Medical Standardization Board, located at Fort Detrick, Frederick, Maryland, publishes DEPMEDS Policies/Guidelines Treatment Briefs,

most recently in July 1990.4 This manual is neither

a set of orders nor standing operating procedures

for the care of individual patients but is the doctrinal

basis for medical care in a theater of combat. It

contains the concept of operation for DEPMEDS

and treatment briefs for the 339 patient conditions

used currently in the development of DEPMEDS

(examples are shown in Exhibit 6-2). It must be

emphasized that these patient conditions were designed to facilitate planning for manpower, equipment, and supply needs; they were never intended

to predict every wartime injury nor were they intended to dictate therapy. The patient conditions,

which are based on a combination of historical data,

computer modeling, experience, and enlightened

speculation, provide planning parameters for medical treatment facilities. Of note is the changing

number of patient conditions, which occur as patient conditions are added, deleted, or coalesced

depending on the threat and changing medical

modeling requirements:

The treatment briefs should be viewed as a living

document that will require continual review for

currency. At periodic intervals particular types of

diseases or injuries will have to be modified due to

the advent of new treatment modalities or the

change in the medical threat.4(p92)

The patient conditions did not change substantially

after the Persian Gulf War.

The DEPMEDS manual also contains specific

policies for specialties (including anesthesiology),

and guidelines for emergency medical treatment,

fluid resuscitation, laboratory tests, the use of cell
123

Deployable Hospitals

savers, and the use of blood. Anesthesiologists and

nurse anesthetists who are deploying with a

DEPMEDS-equipped unit should review the manual

and note the following policies4(p49):

• Pulse oximetry is available intraoperatively

and postoperatively.

• Halothane and isoflurane are the only inhalational anesthetics currently available.

• Nitrous oxide is not available.

• Patients recover in an intensive care unit

adapted for that purpose.

• The care of postoperative patients is one of

the most important responsibilities of anesthesia personnel.

• In-line oxygen monitoring is available (endtidal carbon dioxide monitoring currently

is not available but was recommended as a

part of the monitoring package at the March

1992 update).

• Regional anesthesia kits are supplied for

spinal and axillary blocks only (an epidural

kit has been requested).

• Draw-over vaporizers are available for use

when other methods are unavailable in extremely austere environments.

Most of the equipment used by anesthesiologists is

currently contained in Operating Room MMS D301.

The March 1992 revision strongly recommended that

a separate anesthesia MMS be created to facilitate

accountability, periodic review, maintenance, and

rapid accessibility. The only significant piece of

equipment not included in the Operating Room MMS

for which anesthesia providers have expressed a desire is for a 5-mm flexible, fiberoptic bronchoscope.

This instrument is contained in Central Material Supply Special Augmentation Set D342.

Physiological Monitors

The physiological monitors that are part of

DEPMEDS include electrocardiographs, automated

blood pressure machines, several types of thermometry (including glass oral and rectal thermometers), electronic esophageal stethoscopes, central

venous manometers, transcutaneous peripheral

nerve stimulators, and pulse oximeters. Monitoring of arterial blood gases is considered vital:

DEPMEDS purchased a GEM-STAT blood-gas analyzer (manufactured by Mallinckrodt Sensor Systems, Ann Arbor, Mich.) for the Persian Gulf War

and it was included in the 1990 database. Active

duty TOE units have this monitor.

Resuscitative Equipment

Resuscitative equipment available includes one

defibrillator for each operating room; one external,

noninvasive pacemaker in each Emergency Medical Treatment module; and two invasive, external

pacemakers, all of which are included in each Medical Services Augmentation set (D413) at the fourth

echelon. Gas-powered volume ventilators (the

Ohmeda 7000, manufactured by Ohmeda, Inc.,

Madison, Wis.) and the Ohmeda PAC (portable

anesthesia circuit, manufactured by Ohmeda, Inc.,

Madison, Wis.) unit have been added to the

armamentarium. Pressure transducers are not

part of the DEPMEDS equipment, but were

recommended and requested at the March 1992

update. The Uni-Vent 750 ventilator (manufactured by Impact Medical Corp., West Caldwell,

N.J.), a compact, portable ventilator used to provide

short-term ventilatory support for an intensivecare-unit patient population, was first made available to the U.S. Army Medical Department (AMEDD)

during the Persian Gulf War. Approximately 1,900

units are currently in the DEPMEDS inventory.5

Medical Gases

Medical gases are supplied in the operating room

MMS. Oxygen tanks include the D cylinder for use as

back-up on the Ohmeda 885 Field Anesthesia Machine (manufactured by Ohmeda, Inc., Madison, Wis.)

and the M cylinder for use as the central source. H

cylinders (6,900 L) are also available. The D cylinder

contains approximately 360 L of oxygen and the M

cylinder contains 2,835 L at standard temperature and

pressure. Medical Supply, a part of Medical Logistics,

is responsible for receiving, storing, and issuing all

necessary supplies consumed during an operation,

including delivery of and exchanging of medical gas

cylinders in the operating room. Oxygen tanks are

changed on a regular basis and the potential for errors

related to the oxygen supply exists, making the in-line

oxygen monitor a valuable device. Preventive and

corrective maintenance is very limited. An anesthesiDEPLOYABLE ANESTHESIA EQUIPMENT
Anesthesia and Perioperative Care of the Combat Casualty

124

sodium citrate, metoclopramide, 7.5% bupivacaine

in dextrose, dexamethasone, albuterol inhalers, and

verapamil.

Miscellaneous Equipment

Miscellaneous equipment items that were added

at the March 1992 update include epidural kits,

hygroscopic humidifiers, Y-type blood-administration sets, and 8.5 French central venous catheter

kits. Also added were 3.0- to 6.0-mm (internal

diameter) uncuffed pediatric endotracheal tubes,

22-gauge intravenous catheters, and mini-drip intravenous-infusion sets. At the March 1992 update,

it was also recommended that a discrete monitoring

package be adopted for DEPMEDS. The prototype

for this would be the PROPAQ 106 monitor (manufactured by Propaq Systems, Beaverton, Ore.) and

ideally would include the ability to monitor the

electrical activity of the heart, oxygen saturation,

blood pressure (noninvasive), end-tidal carbon dioxide, and to measure two invasive pressures (ie,

arterial and central venous pressure).

Essential characteristics for a new field anesthesia machine to replace the Ohio 885 were also submitted by anesthesia representatives to the March

1992 update. Shortcomings of the Ohio 885 include

obsolete technology and heavy reliance on compressed gas. Most importantly, because the machine does not meet American Society for Testing

and Materials (ASTM) standards, it cannot be used

during peacetime for training or patient care. Ideally, the new machine would

• be a small, compact, durable, closed-circuit

system;

• be powered by compressed gas (45 psi),

an oxygen concentrator, or an air compressor;

• be a multiagent (isoflurane and halothane)

vaporizer; and

• meet all ASTM standards.

Work on the development of and procurement for

this machine is in progress. Market and industry

surveys, development, field testing, and procurement will probably take 3 to 5 years.

The anesthesia drugs and equipment were selected to provide general anesthesia via mask or

endotracheal tube, with either controlled or spontaneous ventilation; and regional anesthesia including Bier, axillary, spinal, epidural, and peripheral

ologist assigned to a DEPMEDS unit should check

with Medical Logistics once the hospital is set up to

determine not only what replacement equipment is

available but also the extent of the biomedical repair staff’s repair capability.

Blood-Recovery Equipment

Blood-recovery equipment is contained in the

Blood Recovery/Delivery System Augmentation set

(D343) and currently consists of one Haemonetics

Cell Saver 4 (manufactured by Haemonics Corp.,

Braintree, Mass.) machine and the equipment necessary to perform 100 cases (including harnesses,

bags, tubing, sterile fluids, and heparin). The bloodrecovery system is expected to be used in the

preoperative and intraoperative periods in cases of

massive hemorrhage. The system is also approved

for use in cases of gross blood contamination.

Setup and cleaning are the responsibility of the

operating room technicians, and intraoperative use

is the responsibility of anesthesia personnel. Efficient intraoperative use of the blood-recovery system requires a second person besides the primary

anesthesia provider.

A Level 1 blood-warming infusion device (manufactured by Level 1 Technologies, Inc., Rockland,

Mass.) is currently available in DEPMEDS (one Level

1 for every two operating room beds).

Anesthetic Drugs

The pharmacological armamentarium of anesthetics and anesthetic adjuvants available in the

operating room set was revised in March 1992 (Table

6-1). At the onset of Operation Desert Shield (ie, the

build-up phase of the Persian Gulf War) in August

1990, the primary induction agents were pentothal,

ketamine, and diazepam. Maintenance agents were

fentanyl and halothane. Muscle relaxants were

succinylcholine and pancuronium. The local anesthetic agents were lidocaine, bupivacaine, mepivacaine, and tetracaine. Anesthetics that were deleted

at the 1992 update include diazepam, pancuronium,

Demerol (meperidine; manufactured by Sanofi

Winthrop Pharmaceuticals, New York, N. Y.), and

curare. Drugs that had not been available in the

basic Operating Room MMS but were added at the

March 1992 update include phenylephrine,

vecuronium, esmolol, labetalol, nitroglycerin (intravenous preparation), isoflurane, propofol, preservative-free morphine, sufentanil, midazolam,
125

Deployable Hospitals

TABLE 6-1

ANESTHESIA-RELATED DRUGS CONTAINED IN THE BASIC OPERATING ROOM

MEDICAL MATERIAL SETS*

Concentration Quantity or Size

Drug or Amount Dispensed

Concentration Quantity or Size

Drug or Amount Dispensed

Lidocaine ointment 5% 35 g

Lidocaine and USP

epinephrine inj 1% 20 mL

Lidocaine HCl 1% inj 10-mL syringe

Labetolol HCl inj USP† 5 mg/mL 20 mL

Lubricant, ophthalmic — —

Mepivacaine HCl inj† 20mg/mL 50 mL

Midazolam HCl† 5 mg/mL 1-mL vial

Morphine sulfate inj 10 mg/mL 1-mL ampule

Morphine sulfate

inj, preservative-free† — 5-mg vial

Naloxone 0.4 mg/mL 1 mL

Nitroglycerine 5 mg/mL 10-mL vial

Neostigmine 1 mg/mL 10 mL

Nitroprusside† 5 mg/mL 10 mL

Povidone-iodine

topical solution — 3.8 L

Phenylephrine HCl† 1% 1-mL vial

Propofol inj† 10 mg/mL 20-mL ampule

Ringer’s lactate — 1,000-mL bag

Soda lime cartridge — —

Sodium bicarbonate 8.4% syringe 50 mL

Sodium chloride

inj USP — 1,000-mL bag

Sodium citrate and

citric acid† oral solution —

Succinylcholine 20 mg/mL 10-mL vial

Succinylcholine — 1 g powder

Tetracaine — 20-mg ampule

Thiopental sodium inj — 5-g bottle

Vecuronium bromide† — 10 mg powder,

vial

Verapamil† 2.5 mg/mL 2-mL vial

Water for inj, sterile — 5-mL vial

Albumin 25 % 100 mL

Albuterol inhaler† — 17 g

Atropine 0.4 mg/mL 20 mL

Benzoin — 1 pint

Bupivacaine 0.5% 30 mL

Bupivacaine HCl

in dextrose† 7.5 mg/mL 2-mL ampule

CaCl2 100 mg/mL 10-mL syringe

Dyphenhydramine

HCl 50 mg/mL 1 mL

Dantrolene sodium — 20-mg vial

Dextrose in H2O 5% 50-mL bag

Droperidol inj† 2.5 mg/mL 2-mL ampule

Dexamethasone sodium

phosphate inj† 4 mg/mL 5-mL vial

Epinephrine inj USP† 1 mg/mL 1-mL ampule

Epinephrine inj 0.1 mg/mL 10-mL syringe

Esmolol HCl† 10 mg/mL 10-mL vial

Ephedrine sulfate 25 mg/mL 1-mL ampule

Fentanyl citrate inj USP 25 μg/mL 2-mL ampule

Glycopyrrolate inj† 0.2 mg/mL 20-mL vial

Halothane — 250 mL

Heparin sodium 1,000 units/mL 10 mL

Hetastarch in NaCl 500-mL bag —

Hydralazine† 20 mg/mL 1-mL vial

Isoflurane USP† — 100-mL bottle

Isopropyl alcohol USP — 1 quart

Ketamine HCl inj 50 mg/mL 10-mL vial

Lidocaine 40 mg/mL 25 mL, for

infusion

Lidocaine 1% 50 mL

Lidocaine 2% 20-mL vial

Lidocaine HCl +

dextrose† 5% 2-mL vial

inj: injection

*As of March 1992

†Recommended additions from the March 1992 DEPMEDS update. These drugs will have to be approved and then purchased before

they are placed in DEPMEDS hospitals.

Adapted from Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs. Fort

Detrick, Frederick, Md: 1990: App D.
Anesthesia and Perioperative Care of the Combat Casualty

126

nerve blocks. Anesthetic drugs and equipment may

be available for other techniques to be performed,

depending on the experience and innovation of the

anesthesiologist or nurse anesthetist.

Fluid Resuscitation

Fluid resuscitation has been stressed appropriately in the outfitting of DEPMEDS facilities. Lactated Ringer’s solution and normal saline are the

primary crystalloid resuscitative solutions.

Hetastarch and albumin are the colloid solutions

available and are supplied for use in patients whose

estimated blood losses exceed 1,500 mL. Blood

products including packed red blood cells, fresh

frozen plasma, and platelets (which are typically

provided as 200- to 300-mL “six-packs”) are also

available.

DEPMEDS-EQUIPPED HOSPITALS

DEPMEDS-equipped hospitals are designed to

be used in all situations by all four armed services of

the U.S. military. By 1990, the army had decided on

fielding six types of DEPMEDS-equipped hospitals:

general, station, field, evacuation, combat support,

and MASH, which have differing mobility, missions, numbers of operating rooms, numbers and

types of beds, and types of patients. Physically,

DEPMEDS-configured hospitals consist of expandable metal boxes, which, although they are somewhat similar to the hard-walled expandable shelters of the MUST, are really quite different; and

TEMPER (tents, extendable, modular, personnel)

tents, which replaced the MUST program’s inflatable shelters. The equipment needed to make the

International Standards Organization (ISO) shelters and TEMPER tents functional in their various

configurations is contained within MMSs. Electricity

is provided by 100-kW, diesel-powered generators.

The expandable shelters were made to conform

to the dimensions established for cargo containers

by the ISO, and for this reason they are known as

ISO shelters. An ISO shelter is, however, not simply

a box. Its walls are composed of several layers that,

when folded out, can be reconfigured into one or

two additional boxes. Thus, the internal volume of

a single ISO shelter can be doubled (2:1) or tripled

(3:1) (Figure 6-6).

TEMPER tents are the second major component

of DEPMEDS hospitals. They differ from standard

army tents by having a magnesium-alloy frame

instead of wooden poles and a covering that is made

of vinyl-covered fabric rather than canvas. In contrast to standard-issue tents, TEMPER tents have

fabric floors, a feature that not only limits dust and

mud within the patient treatment areas but also

makes possible more-efficient cooling and heating

of the enclosed space. Individual modules are 8 ft

long x 20 ft wide and are extended into either twoor eight-section tents (Figure 6-7). The triage/emergency medical treatment/preoperative module and

the postoperative/intensive care units are both composed of eight-module TEMPER tents.

Each DEPMEDS hospital is composed of the same

integral components, including (a) the patient treatment areas: operating room, emergency medical

treatment area, intensive care unit, intensive care

ward, and minimal care ward; and (b) the ancillary

support areas: the clinical laboratory and blood

bank, the radiology area, and the pharmacy, among

others. The exact configuration of these various

areas can be changed depending on the tactical

situation and patient flow. These functional areas

are not likely to change with Medical Force 2000

(MF2K, which is discussed later in this chapter); the

Fig. 6-6. The construction of a 2:1 ISO (International

Standards Organization) shelter (1–5). The side wall of

the original box consists of three individual walls that are

folded out to enclose the additional space. A 3:1 ISO

shelter can be formed by a similar process performed on

the opposite wall (6). Adapted from Department of the

Army. Deployable Medical Systems. Washington, DC: Headquarters, DA; 1990. TC 8-13: 3-21–3-26.
127

Deployable Hospitals

Fig. 6-7. Two TEMPER tent modules have been combined to form

the tent on the left, while eight

modules have been combined to

form the tent shown in the rear.

TEMPER: tents, extendable, modular, personnel.

equipment contained in them, though, will continue

to change as technological advancements are made.

Patient Care Areas

The operating room in a DEPMEDS facility is a

3:1 ISO shelter, which houses two operating tables

and the necessary equipment to perform two operations simultaneously (Figure 6-8). The layout of the

operating room specifies that both operating room

tables face in the same direction, which allows the

anesthesia provider more flexibility in monitoring

patients. The anesthesiologist is equipped with an

Ohmeda 885 Field Anesthesia Machine, Ohmeda

7000 volume ventilator, anesthesia cart, intravenous infusion pole, and suction from an operating

room suction machine. The main oxygen supply

(two M cylinders per operating room table) and

both a fluid and a blanket warmer are all located

within the operating room. The operating room

layout is schematic and can be changed depending

on the type of surgery. Having two operating room

tables in one room allows personnel to be used more

efficiently and creates a mutual back-up system for

equipment and supplies. An associated operating

room preparation MMS was supposed to be available, but this appears not to have been deployed.

The emergency medical treatment area is set up

to provide initial medical evaluation and treatment,

triage, and resuscitation, and to serve as a

preoperative holding area when no surgical delay is

anticipated (Figure 6-9). Each emergency medical

treatment area has space for 12 litter patients and is

capable of monitoring vital signs including oxygen

saturation and the electrical activity of the heart in

a limited number of patients. It is equipped to

provide Advanced Trauma Life Support (ATLS;

discussed in Chapter 1, Combat Trauma Overview)

care to all patients, and mechanical ventilation to a

very limited number (but only to two patients at a

time). Depending on the size of the hospital, two or

more emergency medical treatment sets were designed into the new MF2K structure to accommodate

the hypothetical number of incoming casualties.

The intensive care unit is designed to provide

care to the most seriously injured and to sick patients of all types (Figure 6-10). Each intensive care

unit has 12 beds and can mechanically ventilate six

patients using volume ventilators. The unit is capable of monitoring the patients’ electrocardiographic status and oxygen saturation but, as is the

case throughout DEPMEDS, does not currently have

the capability for any type of invasive blood pressure monitoring except central venous pressure via

manometry. The intensive care unit may also be

used as a postanesthetic recovery area.

The intermediate care ward is designed to provide care to acutely injured or sick patients of all

types. The ward does not normally care for patients

who require continuous monitoring or life-support

devices, but the level of acuity can vary greatly

depending on the type of conflict or catastrophe.

The intermediate care ward can also serve as a

specialty area (ie, a burn ward). It has the capacity

for 20 patients.

The minimal care ward provides care to medical

and surgical patients who are ambulatory and partially self-sufficient. No intravenous fluids or

parenteral medications are administered on this

ward. The primary focus on the ward is the physical

and psychological conditioning of soldiers expected

to return to duty. The ward has a capacity of 40

patients housed in two general purpose, large (GPL)

tents.

The relative mix of anesthesia-relevant MMSs,

ISO shelters, and TEMPER tents depends on the

type of hospital. The authorization matrix for the

1990 version of DEPMEDS is shown in Table 6-2.

Updating of the matrix is continuous, however, and

this information has already been changed by MF2K.
Anesthesia and Perioperative Care of the Combat Casualty

128

10: Stand, basin, folding

11: Apparatus, electrosurgical

12: Stool, revolving

13: Pail

14: Cloth, frame

15: Apparatus, suction

25: Air conditioner/heater

1: Cabinet, pharmacy, base

2: Cart, anesthetic equipment

3: Cabinet, pharmacy, upper

4: Apparatus, anesthetic

5: Table, operating, field

6: Regulator, thermo

7: Table, surgical instrument

8: Table, surgical instrument and dressing

a

b

Fig. 6-8. (a) The recommended arrangement of the DEPMEDS operating room medical material set in a 3:1 ISO shelter.

(b) The two operating tables in a 3:1 ISO face in the same direction, which allows the anesthesia provider more

flexibility in monitoring patients. DEPMEDS: Department of Defense’s Deployable Medical Systems; ISO: International Standards Organization. Diagram (a) : Reprinted from Department of the Army. Deployable Medical Systems.

Washington, DC: Headquarters, DA; 1990. TC 8-13: 2-2.
129

Deployable Hospitals

1: Chest, medical instrument, six-drawer

2: Chest, medical instrument, #3 field

3: Chest, medical instrument, two-shelf

4: Cart, resuscitation, mobile

5: Chest, medical instrument (utility)

6: Refrigerator-freezer, mechanical

7: Stand, surgical instrument

8: Stand, basin, folding

9: Light, floor, operating

10: Sink unit, surgical

11: Table, folding legs, laboratory

12: Litter

25: Air conditioner/heater

1: Chest, medical instrument, two-shelf

2: Chest, medical instrument with 22-drawer

insert

3: Cart, resuscitation

4: Desk, field with folding chairs

5: Light, floor, operating and exam

6: Cart, surgical dressing

7: Refrigerator-freezer

8: Shelf, chrome, 1848

9: Sink unit, surgical

10: Frame, cloth basket, folding

11: Stand, basin, folding

12: Bed, adjustable, hospital

25: Air conditioner/heater

Fig. 6-9. The recommended arrangement of the DEPMEDS triage/emergency medical treatment area/preoperative

room medical material set in an eight-module TEMPER tent. This facility may or may not be connected to the operating

room by an interposed operating room preparation area medical material set. DEPMEDS: Department of Defense’s

Deployable Medical Systems; TEMPER: tents, extendable, modular, personnel. Reprinted from Department of the

Army. Deployable Medical Systems. Washington, DC: Headquarters, DA; 1990. TC 8-13: 2-36.

Fig. 6-10. The recommended arrangement of the DEPMEDS postoperative/intensive care unit medical material set in

an eight-module TEMPER tent. This facility would be connected to the end of the operating room medical material set

opposite the triage/emergency medical treatment area/preoperative room medical material set. DEPMEDS: Department of Defense’s Deployable Medical Systems; TEMPER: tents, extendable, modular, personnel. Reprinted from

Department of the Army.Deployable Medical Systems. Washington, DC : Headquarters, DA; 1990. TC 8-13: 2-32.
Anesthesia and Perioperative Care of the Combat Casualty

130

TABLE 6-2

DEPLOYABLE MEDICAL SYSTEMS–MEDICAL MATERIAL SET AUTHORIZATION MATRIX

DEPMEDS-Equipped Hospitals (Number of Sets)

Medical Material Set MASH CSH EVAC STA 300 STA 500 FH GH

Operating room 2 2 3 1 2 3 3

Triage area 1 1 1 1 1 3 1

Intensive care unit 5 4 4 2 4 3 8

Intermediate care 0 4 8 9 15 9 30

Minimal care 0 4 10 5 8 9 15

Ancillary Support Areas

The laboratory section of a DEPMEDS-equipped

facility consists of two parts: the clinical laboratory

and the blood bank. The clinical laboratory provides

basic hematology, chemistry, urinalysis, microbiology, and serology; cytology and pathology can be

performed only if an augmentation team with equipment is added to the hospital. The complete list of

tests provided is contained in the DEPMEDS Policies/Treatment Briefs; Table 6-3 includes only tests of

particular interest to anesthesiologists.

There are two types of blood bank sections: the

Liquid Blood Bank MMS D304 and the Liquid/

Frozen Blood Bank MMS D404. The liquid blood

bank can store 500 units of packed red blood cells

and can issue 250 units for transfusion in a 24-hour

period. Each patient’s blood is ABO grouped and

Rh typed. A single-tube (major-side saline, immediate spin) cross-match is performed on each patient. The liquid blood bank can draw and type 180

units of fresh whole blood for extreme emergencies.

The liquid/frozen blood bank can store 500 units of

packed red blood cells, 485 units of frozen red blood

cells, 10 units of fresh frozen plasma, and 5 packs of

platelets, and is capable of reconstituting 180 units

of frozen red blood cells per 24 hours. It can issue

up to 250 units of blood for transfusion in a 24-hour

period. It has the same emergency blood-drawing

capabilities as the liquid blood bank. The storage

and transfusion shelf life of the different blood products was established in accordance with the Military

Blood Program 2004 Study (which is available from

U.S. Army Medical Department [AMEDD] Center

and School, Fort Sam Houston, San Antonio, Tex.).

Several assumptions and planning factors are

used in calculating blood usage:

• Only blood that is actually to be transfused

is ordered.

• Patients with hematocrits of 0.21 or lower

will frequently require blood transfusions.

• Single units of blood will not be requested.

• Fresh frozen plasma is transfused at a ratio

no greater than 1 unit per 10 units of red

blood cells infused into the same patient.

• Platelets are transfused at a ratio no greater

than 1 unit per 20 units of red blood cells

infused into the same patient.

• Each platelet transfusion is expected to raise

the platelet count in a 70-kg man by 30,000 to

80,000 platelets/mm3.

Both platelets and fresh frozen plasma supplies are

extremely limited in the theater of action, and the

current recommendation is that they be used only

for documented thrombocytopenia or coagulopathy.

The transfusion ratios were established using accepted standards of transfusion medicine in trauma

settings. However, these are guidelines, and the

decision to administer any blood products is a clinical one that is the medical officer’s responsibility. A

more detailed discussion can be found in Chapter

15, Military Transfusion Practice.

Radiographic support is provided by a fixed,

high-capacity, combination X-ray and fluoroscopy

unit, and by portable machines. The radiographic capabilities include plain X-ray examinations

MASH: Mobile Army Surgical Hospital; CSH: Combat Support Hospital; EVAC: Evacuation Hospital; STA 300: Station Hospital, 300

beds; STA 500: Station Hospital, 500 beds; FH: Field Hospital; GH: General Hospital

Adapted from US Department of the Army. Deployable Medical Systems: Tactics, Techniques, and Procedures. Washington, DC:

Headquarters, DA; 7 Dec 1990. Training Circular 8-13, Table 2-1, p 2-24.
131

Deployable Hospitals

TABLE 6-3

LABORATORY PROCEDURES PERFORMED AT THE THIRD AND FOURTH ECHELONS

Test Task No. Description Third Echelon Fourth Echelon

Chemistry E001 Blood gas estimation + +

E002 Electrolyte levels (Na+, K+, Cl–, HCO3)+ +

E003 Total serum protein level + +

E004 Urinary protein level + +

E005 Serum creatinine level + +

E007 Serum amalyse level + +

E008 SGPT level + +

E009 CK level + +

E010 Blood glucose + +

E011 BUN level + +

E012 Serum bilirubin + +

E013 Spinal-fluid sugar + +

E014 Spinal-fluid protein + +

E015 SGOT level — +

E017 Calcium level + +

Hematology/Urinalysis E020 CBC (WBC, Hgb, Hct) + +

E021 White cell count + +

E022 Hematocrit level + +

E024 White cell differential count + +

E025 Prothrombin time + +

E026 PTT + +

E028 Spinal fluid cell count and differential + +

E029 Urinalysis with specific gravity + +

E030 Microscopic urinalysis + +

E031 Platelet estimate + +

E032 Platelet count + +

E033 Fibrinogen level and fibrin split products — +

SGPT: serum glutamic-pyruvic transaminase (alanine aminotransferase); CK: creatine kinase; BUN: blood urea nitrogen; SGOT:

serum glutamic-oxaloacetic transaminase (aspartate aminotransferase); CBC: complete blood count; WBC: white blood cell; Hgb:

hemoglobin; Hct: hematocrit; PTT: partial thromboplastin time

Adapted from Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs. Fort

Detrick, Frederick, Md: 1990: 82.

and some special studies (eg, upper gastrointestinal series, intravenous pyelogram, and singleshot angiography). Although only the portable

X-ray unit is available in the operating room, the

unit can be taken throughout the hospital. A refined C-arm module is in the process of approval

and was suggested for procurement and fielding by

the year 2000.

The pharmacy stocks a number of drugs that are

not part of the operating room MMS. Once the

hospital has deployed, the actual placement and

distribution of drugs may vary depending on the

standing operating procedures of the hospital. The

handling of controlled substances will likewise vary

depending on the situation and the guidance of the

hospital commander.
Anesthesia and Perioperative Care of the Combat Casualty

132

DEPLOYABLE HOSPITALS IN THE PERSIAN GULF WAR

Forty-four DEPMEDS-equipped hospitals were

deployed to Saudi Arabia in support of the Persian

Gulf War (Table 6-4).6 The enormous size and

complexity of a typical DEPMEDS-equipped hospital is apparent in Figure 6-11, which shows two

evacuation hospitals collocated in the same base

camp in the Arabian desert during the Persian Gulf

War. Ad hoc forward surgical teams (FSTs) were

also deployed and were used in support of combat

arms units far forward in the combat zone. These

elements were not DEPMEDS-equipped owing to

mobility constraints; important components of

DEPMEDS equipment (eg, ISO shelters, TEMPER

tents, C-arms, laundry units, and other bulky equipment items) were found to be incompatible with

high mobility. The ISO shelters require specially

designed dolly sets for their movement; they are not

designed to be transported by truck, a significant

drawback in a war characterized by movement.

The DEPMEDS equipment is too heavy and too

complex, and the reassembly is too time-consuming

for modern maneuver warfare. The afteraction

reports from Operation Desert Storm are replete

with statements that hospital equipment cannot be

moved rapidly enough to support the needs of a

highly mobile army:

There were strong feelings in regard to the mobility

of DEPMEDS equipment, especially in this conflict

when hospitals had to move long distances in short

periods of time, and then rapidly prepare to receive

casualties.7(p8–24)

. . . .

A hospital following the forward maneuver units

and providing surgical care should be capable of

establishing the Emergency Medical Treatment

(EMT) section and one to two operating rooms

(OR) in 1 to 2 hours, and the entire hospital in 6 to

8 hours. The hospital should be able to break down

and be prepared to move in less than 12 hours. The

hospital should be capable of moving in sandy and

rough terrain.

In Operation Desert Storm, most forward hospitals

took 3 to 4 hours to have an operating room set up,

6 to 8 hours to set up the EMT section, and almost

24 hours to establish the entire hospital. Thirty-six

to 48 hours were required to break down and pack

the hospital. Thirty 5-ton trucks were required to

move the hospital, with only approximately 10

contained in the unit TOE. Each truck also had an

attached dolly set. Each dolly set required 8 to 12

people a half hour (or more at night) to attach. The

dolly set had only a 12-inch clearance, causing it to

be easily hung up, in the front, in rough terrain

(offroad).7(p1–11)

Hospitals deployed during the Persian Gulf War

included both active duty and reserve or National

Guard units. By August 1990, very few active duty

units had converted to DEPMEDS. Those that had

invariably suffered from shortages of equipment

and pharmaceuticals. The training sets that reserve

and National Guard hospitals were issued contained only minimal essential equipment, while the

complete hospital sets were placed in storage as

prepositioned material configured in units and sets

(POMCUS) or primary mobilization stations

(PRIMOB). Shortages were attributed to the newness of the system, delays in purchase from the

industrial base, and sometimes delayed decisions

from clinical groups that reviewed equipment and

drug selection. The following priority sequence

was used in fielding DEPMEDS:

1. unequipped reserve and National Guard

units,

2. active duty, rapid-deployment units,

3. regional training sites, and

4. active duty TOE hospitals.

At the time of deployment, the decision was

made to modernize in theater. Therefore, equipment sets that had been packed for long-term storage were lacking (ie, short) some equipment and

were not functionally operational when they arrived in country. These equipment shortages led to

the ship-short concept: the package of missing equipTABLE 6-4

HOSPITALS DEPLOYED TO

SAUDI ARABIA (1990)

Hospital Number Deployed

Mobile Army Surgical Hospital 8

Combat Support Hospital 9

Evacuation Hospital 22

Station Hospital 1

Field Hospital 3

General Hospital 1

Total 44
133

Deployable Hospitals

Fig. 6-11. Two evacuation hospitals,

the 148th in the distance on the left

and the 410th in the near right, deployed in the Kuwaiti Theater of Operations during the Persian Gulf War.

TEMPER tents form much of the central portion of the 410th. ISO shelters

can be identified by their lighter color.

Hospital personnel are billeted in the

complex of canvas tents that occupy

the right side of the hospital. TEMPER: tents, extendable, modular, personnel; ISO: International Standards

Organization. Photograph: Courtesy

of Public Affairs, Office of The Surgeon General, US Army.

pharmaceuticals if such were requested by deployed

physicians. In addition to standard U.S. Army

channels, sources for equipment procurement included local purchase, Air Force logistics, and even

personal mail from hospitals in the continental

United States. All hospitals were operational by the

onset of the ground war.

Work load, patient type, and frequency of movement varied widely among the 44 DEPMEDS hospitals deployed to Saudi Arabia. Patient categories

included U.S. and allied military battle injury and

nonbattle injury, civilian disease and injury, and

Iraqi prisoners. The variety of patient conditions

encountered emphasized the need for the DEPMEDS

system to be able to support all aspects of clinical

anesthesia: emergency and elective (neurosurgical,

thoracic, abdominal, vascular, etc), and regional,

obstetrical, and even pediatric anesthesia. The percentages of multiple-trauma cases varied widely in

the afteraction reports.7

The most frequently used anesthetic agents included isoflurane, succinylcholine, vecuronium,

thiopental, ketamine, local anesthetics, and fentanyl.

By far the most commonly used general anesthetic

technique was a rapid-sequence induction with tracheal intubation, followed by a balanced anesthetic.

Packed red blood cells were frequently used, but

the use and availability of fresh frozen plasma or

platelets was minimal to nonexistent. Oxygen supplies, particularly for refilling tanks, were frequently

inadequate. Sterile water was supplied in plastic

bottles.

The Persian Gulf War provided the first true test

of the DEPMEDS system. As with any new system,

problems were encountered and weaknesses uncovered; nevertheless, the conversion to DEPMEDS

ment (ie, the push packet) would be sent to the units

in theater as soon as it could be procured. Correction of shortages was actually a complex process; it

involved six independent, functional areas that procured equipment and supplies. Delivery to specific

hospitals in theater then required the coordinated

efforts of the Medical Supply, Optical, and Maintenance (MEDSOM) Battalion (which is now called

the Medical Logistics Battalion).

Communication—both between hospitals and

between air force and army evacuation assets—was

frequently a problem. Deployed personnel cited

premobilization instruction in theater communications networks and standing operating procedures

as critical information to help avoid future problems.

Afteraction reports by anesthesiologists (60N)

and nurse anesthetists (66F) expressed concerns

about the following missing equipment:

• noninvasive blood pressure machines,

• pulse oximeters,

• electrocardiographs,

• adequate suction devices,

• regional anesthesia kits and needles,

• oxygen tubing, and

• medications (eg, isoflurane, vecuronium,

midazolam, reversal agents, and pentothal).

It must be emphasized, however, that many of the

items and drugs (including isoflurane, vecuronium,

and even nitrous oxide) that deployed personnel

expected to have, were never on the TOE for

DEPMEDS hospitals, and therefore should not have

been expected. However, the Office of The Surgeon

General decided to attempt to provide non-TOE
Anesthesia and Perioperative Care of the Combat Casualty

134

was completed in theater and all hospitals were

ready by the time the ground offensive commenced.

Overall, the system worked well under often adverse conditions, although the limited number of

casualties makes an assessment of DEPMEDS’ true

value difficult to make. The Defense Medical Standardization Board will continue to conduct a review of equipment and drugs approximately every

2 years; changes will be made as necessary. The

system will always be in transition so that it can

keep up with changes in warfare, medical doctrine,

and new developments in medical technology. The

structure of the medical force will continue to evolve.

Changes in war-fighting doctrine, changes in the

nature and sophistication of threat forces, and the

increasing requirement for AMEDD to be involved

in peacetime missions will necessitate constant

changes and force modifications.

MEDICAL FORCE 2000

While DEPMEDS is essentially a system describing

the characteristics of hardware, Medical Force 2000

(MF2K) deals not only with equipment but also with

personnel and organization. Four types of hospitals—MASH, combat support, field, and general—

and a medical holding company were initially envisioned by MF2K. Under MF2K, station and evacuation

hospitals will be deleted from the system, and the

MASH configuration will change dramatically. These

changes will largely be made to prevent duplication in

the system and to streamline the patient-evacuation

flow. The original concept calls for the MASH to be

changed from a 60-bed, DEPMEDS-configured facility to a more-mobile, 30-bed, non-DEPMEDS unit.

The MASH remains a surgical unit only, with minimal medical-treatment or patient-holding capability. Likewise, for mobility considerations, the MASH

will not use ISO shelters. The combat support, field,

and general hospitals will remain DEPMEDS

equipped. The numbers of anesthesiologists and

nurse anesthetists proposed for each type of hospital are found in Table 6-5. The third echelon includes

the MASH, combat support hospital, and medical

holding company; the fourth echelon includes field

and general hospitals. Like DEPMEDS, MF2K is

subject to revision, the process being known as the

medical reengineering initiative (MRI).

The MF2K designs for the combat support, field,

and general hospitals are built using a four-module

concept:

• Hospital Unit, Base (HUB)

• Hospital Unit, Surgical (HUS)

• Hospital Unit, Medical (HUM)

• Hospital Unit, Holding (HUH)

The HUB, a base, can operate independently and is

located in each hospital as the initial building block.

The exact composition of the base may vary among

the different hospitals. The other modules contain

the necessary equipment, supplies, and assigned

personnel to accomplish the particular mission (eg,

*60N

†66F

MASH: Mobile Army Surgical Hospital; CRNA: Certified Registered Nurse Anesthetist

Source: Perkins DE. Colonel, Medical Corps, US Army. Washington, DC: Walter Reed Army Medical Center. Personal communication, June 1995.

TABLE 6-5

MEDICAL FORCE 2000 ANESTHESIA STAFFING

Hospital Anesthesiologists* CRNAs†

MASH 1 4

Combat Support Hospital 3 15

Field Hospital 1 2

General Hospital 3 15

(Number)

to provide an operating room capability for a certain number of operating tables, in the case of the

HUS). Future AMEDD force-structure doctrine, as

expressed in MF2K and MRI, will emphasize the

tailoring of medical assets for the proposed mission, an undertaking less easily accomplished with

previous DEPMEDS-configured hospitals designed

for a high-intensity war.

Mobile Army Surgical Hospital

The original MF2K design for the MASH converted the existing 60-bed hospital to a highly mobile 30-bed facility designed to function in the rear

area of the division or the forward area of the corps.

Surgical capability was based on three operating

room tables for general, orthopedic, and thoracic

surgery. Preoperative and postoperative acute nursing care for up to 30 patients was provided in three

wards. The following services were planned: pharmacy, clinical laboratory, liquid-blood bank, radi-
135

Deployable Hospitals

ology, and food services. Unfortunately, it soon

became apparent that the reduction in weight and

volume was less than desired: in 1992, a MASH

weighed 240,500 lb and occupied 17,514 ft3, and the

MF2K MASH weighed 184,331 lb and occupied

15,498 ft3.

8

 In the future, neither the 30- nor the 60-

bed MASH will be fielded.

The configuration of the army’s forward surgical

hospitals has undergone a great deal of study, analysis, and field testing during the last half century and

an entirely satisfactory design is not yet available.

In no other type of hospital is the tension between

the perceived need for ever-increasing medical sophistication and complexity and the military logistical requirements for a high degree of strategic and

tactical mobility more apparent. One of the implicit

assumptions behind DEPMEDS was to match the

standards of civilian hospitals while also being able

to care for the massive casualty load expected to be

generated by a high-intensity war in Europe. Planners tacitly assumed that transportation capability

would appear when needed. In essence, bed capacity and sophistication of care were favored over

mobility and sustainment. The MASH, which has

long been criticized as being too heavy and bulky to

have the needed degree of strategic or tactical mobility, was more affected by this design philosophy

than was any other DEPMEDS hospital. The commander of the 5th MASH during the Persian Gulf

War has written of the need to reverse the DEPMEDS

approach to the design of deployable hospitals by

first defining weight and volume limits compatible

with strategic and tactical mobility. Weight and

volume limits should then be used to determine the

number of beds, surgical capability, and staffing.9

Forward Surgical Team

The MASH is to be replaced by a TOE unit to be

known as the FST. This unit, of which at least 30 are

planned, will have 2 operating tables and 8 beds. It

will be staffed by 3 general surgeons and 1 orthopedic surgeon; 2 nurse anesthetists; 1 each operating

room nurse, intensive care nurse, medical-surgical

nurse; and 11 medics. The FST will be housed in

lightweight collective protective equipment developed by the U.S. army and known as chemical

biological protective shelters (CBPS). The tents are

made of synthetic materials, and will be moved in

six high-mobility, multipurpose, wheeled vehicles

(HMMWVs) (Figure 6-12). The CBPS, which looks

superficially like the Vietnam War–era MUST shelter (see Figure 6-4), has a rib structure and is inflated by a compressor integral to the HMMWV.

The inflated, insulated CBPS has airlocks for both

litter and ambulatory access.10

An FST is eminently air-transportable and can,

with its organic vehicles, be moved by two C-141

missions (or possibly only one). By way of contrast,

the 1990 version of the MASH required no less than

32 C-141 missions for its deployment.9 Standard

DEPMEDS MMSs will not be used. Supplies will be

available for 72 hours of continuous operations,

during which period 30 major operations can be

performed. Supplies include 60 units of Group O,

Rh-negative blood.

The original plan called for the FST to be collocated with a brigade- or division-level medical company, with the patient flow being through the medical company. The critically injured casualties were to

be sent directly to the FST, with the remainder of the

casualties to be evacuated after resuscitation to thirdechelon hospitals. Because a medical company may

not always be available, or because logistical and

personnel constraints may have reduced the capability of the medical company, an additional option has

been formulated: the FST can be deployed with both

a holding and a treatment squad, the combined unit

being called a Medical Readiness Task Force.

Command and control of the FST was to have

been from the combat support hospital to which the

FST was originally attached (but not part of) when

not deployed, but it is now likely that the FST will

be controlled by the corps-level medical brigade.

Regardless of the resolution of the command-andcontrol issues, today’s FST is nearly identical in form

and function to the forward battlefield surgical team

of World War II (see Figures 6-1 through 6-3).

The effect of advanced technology has been more

incremental than revolutionary on AMEDD’s ability to care for gravely wounded, nontransportable

casualties. Numerous incremental changes, however, can have a significant total impact. Compare

the following points with the list of essential equipment that was compiled by World War II surgeons

(see Exhibit 6-1):

1. Transportation is now accomplished on

HMMWVs, which are much more mobile

and capacious than jeeps.

2. Modern lighting, including the use of headlights by the surgeons, is a fundamental

improvement on previous equipment. This

is an example of a seemingly minor change

that is, in fact, extremely beneficial to surgeons and therefore to combat casualty care.

3. Heavy oxygen cylinders and other equipment need no longer be transported to
Anesthesia and Perioperative Care of the Combat Casualty

136

a

c

b

forward hospitals. Oxygen concentrators

are part of DEPMEDS equipment, and oxygen can be manufactured in situ.

4. The vagaries and possible complications

of using fresh blood donations have been

obviated by the availability of the hospital’s

own blood bank and the blood transfusion

program.

5. Autoclaving is not used in FSTs; surgical

instruments are chemically sterilized. This

improvement has relieved the logistical

demands of transporting heavy autoclaving equipment.

6. The laundry function of the hospital has

been supplanted by the use of disposable

towels, gowns, sheets, and other linen.

7. CBPS tents are made of a high-performance

fluoropolymer/aramid laminate, in contrast to the heavy canvas that has been

used since at least World War I. The lightweight synthetic material can be decontaminated easily and protects personnel

inside against chemical and biological

warfare agents (liquid and vapor). In addition, individual CBPS units can be connected to make complex collective protection modules.10 These improvements may

provide a more pleasant, climate-controlled environment for casualties and

medical personnel, but they do not necessarily translate directly into lower mortality in combat casualty care.

Anesthesiologists in command-and-control positions need to assure the proper use of the FST. In

a conventional war, in which the casualty load may

Fig. 6-12. The deployable rapid assembly shelter (DRASH) was used in early

prototype forward surgical teams

(FSTs), before the decision was made

to use the chemical biological protective shelter (CBPS). These photographs

of DRASHs were taken during a field

exercise carried out by the 274th Forward Surgical Team of the 44th Medical Brigade, Fort Bragg, North Carolina,

in November 1995. They illustrate some

of the similarities to and changes from

forward surgery during World War II

(see Figures 6-1 through 6-3). (a) The

entire team and its equipment are deployed in six high-mobility, multipurpose, wheeled vehicles (HMMWVs). (b)

The FST works in three interconnected

shelters. The first tent is for receiving

and resuscitating casualties; the second contains two operating tables,

draw-over anesthesia equipment, and

surgical instruments; and the third,

which has eight beds, is the intensive

care and recovery area. The DRASH

could be set up and made fully functioning within 1 hour; an individual

CBPS, using only three men, in 15 minutes.1

 (c) An actual operation is seen in

progress in the operating tent. (1) Gander TJ. Jane’s NBC Protection Equipment.

5th ed. Surry, United Kingdom: Jane’s

Information Group Limited; 1992:

203. Photographs: Courtesy of Major

Thomas E. Knuth, MD, MPH, Medical

Corps, US Army; Eisenhower Army

Medical Center, Fort Gordon, Ga.
137

Deployable Hospitals

fluctuate in a widely unpredictable manner, the FST

should be used to care for only the critically

wounded, the transportable casualties being evacuated to the combat support hospital. If this is not

done, the meager resources of the FST may be exhausted just when they are needed to care for an

influx of gravely wounded soldiers. Members of

the FST and commanders of medical companies in a

position to refer casualties must understand the role

of the FST in the overall context of field medical

support. By way of contrast, in operations other

than war (OOTW), such as when an FST is deployed

to support a small unit not engaged in combat

operations, the FST will probably assume treatment

functions going beyond the exclusive care of the

critically wounded.

Combat Support, Field, and General Hospitals

The mission of the combat support hospital is to

stabilize patients for further evacuation and to return to duty those soldiers who fall within the corps

evacuation policy. This hospital is capable of handling all types of patients and will be employed in the

corps area. Surgical capability is based on eight operating room tables (each used for 18 h/d), for a surgical

capacity of 144 operating room–table hours per day.

Hospitalization for up to 296 patients includes 96

intensive care beds. The combat support hospital

has, organic to its TOE, 35% of the vehicles needed

for a tactical move; it is DEPMEDS configured.

The field hospital provides hospitalization for

general classes of patients and reconditioning or

rehabilitating services for those who can return to

duty within the theater evacuation policy. Most

patients at this facility will be there for rehabilitation. The field hospital will usually be located in the

communication zone. Hospitalization for up to 504

patients includes 36 intensive care beds. Surgical

capability is based on two operating room tables,

for a capacity of 24 operating room–table hours per

day. All movement requirements are the responsibility of theater transportation units. This hospital

is DEPMEDS configured.

The general hospital, a 476-bed facility, serves as

the main conduit for patient evacuation to the continental United States. It provides stabilization and

hospitalization for general classes of patients. Surgical capability is based on eight operating room

tables for a capacity of 144 operating room–table

hours per day. Intensive nursing care is available

for up to 96 patients. The general hospital relies on

theater transportation units for movement and is

DEPMEDS configured.

The characteristics of U.S. Army deployable hospitals continue to change. The need for change

arises from the design of MF2K deployable hospitals, which was based on a high-intensity NATO

war-fighting scenario that anticipated vast numbers of combat casualties. The recent U.S. Army

experience in the Middle East, Somalia, Haiti, and

Bosnia suggests a less apocalyptic battlefield. To

meet the multiple deployment contingencies in

the early 21st century, the MRI envisions one

basic hospital design (not the seven of the original DEPMEDS or the four of MF2K), composed of

small but self-sufficient modules. The MRI hospital

size and the mix of its beds (eg, intensive care,

minimal care) will differ from that of DEPMEDS

hospitals. The basic hospital will consist of 248

beds: 48 in intensive care and 200 in intermediate

care. Minimal care beds will be provided by a

separate medical detachment that will be added to

the basic hospital as needed. The basic hospital

design calls for five operating tables disposed in

three operating room modules. Two of these modules will have two tables each; the third will have

one table plus a C-arm for radiographic studies and

an operating microscope. The major component of

the basic hospital, an 84-bed module, is fully

deployable forward with one of the two-table operating room modules.

The new MRI hospital will be able to provide

general, orthopedic, thoracic, and oral maxillofacial surgical care. Neurosurgery and eye, ear, nose,

and throat surgical capabilities can be added to

the basic hospital by attaching a Hospital Augmentation Team–Head and Neck, which will include

computed tomography capability. Additional Hospital Augmentation Teams are proposed, including

those for Renal Dialysis, Infectious Disease Pathology, and OOTW. Typically civilian medical

and public health problems are likely to be encountered in OOTW, and that team will include a pediatrician, pediatric nurse practitioner, community

health nurse, obstetrician–gynecologist, midwife,

preventive medicine physician, and primary care

physician. DEPMEDS equipment, including shelters, will be used in the basic MRI hospital. Lighterweight shelters, based on the recently fielded

CBPS system, may become available in the near

future.

MEDICAL REENGINEERING INITIATIVE
Anesthesia and Perioperative Care of the Combat Casualty

138

Fig. 6-13. The USNS Comfort as viewed

from the stern. The helicopter flight deck,

designated by the cross, is forward. In

addition to having access by two elevators, one next to the helicopter flight

deck and one forward, casualties can

enter the ship through two water-level

loading portals. The Comfort and her sister, the Mercy, each have an overall length

of 894 ft, a beam of 105 ft 9 in., a draft of

32 ft 9 in., a displacement of 69,360 tons,

a maximum sustained speed of 17.5 knots,

and an endurance of 13,420 nautical

miles. Photograph: Courtesy of Colonel

James Collins, MD, Medical Corps, US

Army, Commandant, Uniformed Services University of the Health Sciences,

Bethesda, Md.

A major difference between the MRI hospital and

its DEPMEDS/MF2K predecessors is the heavy

emphasis in the former on telemedicine and hospital information and communications systems. At

present the order of priority will be to develop (1)

intrahospital communication with telephones, either wired or cellular; (2) local and wide-area networks for interhospital communications; (3) digital

radiology; and ultimately, (4) full-motion video

teleconsultation.

The proposed MRI hospital will be deployed to

both the corps and the echelon above corps, differing only in that the latter may have fewer organic

transportation assets and therefore will be less

mobile. Far forward resuscitative surgery will be

provided by FSTs as proposed in MF2K.

SUMMARY

A modern army must take a hospital system with

it. To be useful, the deployed hospitals must have

some degree of strategic and tactical mobility. Tactical mobility is essential for hospitals that are to

care for combat casualties since, to be optimally

effective, surgical care must be rendered far forward on the battlefield. During World War II, this

was achieved by attaching small teams of surgeons

and anesthesia providers to platoon-sized units from

field hospitals. Austere surgical hospitals in tents

were set up in the division rear area, where they

were collocated with medical units organic to the

division. The MASH, a TOE version of the World

War II surgical team–field hospital platoon, was

HOSPITAL SHIPS

The U.S. Navy’s hospital ships are the ultimate

deployable hospitals. Although the ships are obviously not AMEDD assets, U.S. Army anesthesia

providers need to know about their capabilities

because of the increasing interdependence of the

nation’s military medical services. The U.S.N.S.

Mercy (T-AH 19) and Comfort (T-AH 20) were originally 80,000-ton supertankers. During the mid 1980s

they were converted into hospital ships with a 50-

bed casualty receiving area, 12 operating rooms,

500 acute care beds (20 recovery room, 80 intensive

care, and 400 intermediate care beds), and 500 minimal care beds (Figure 6-13). Staffing consisted of 77

physicians, 160 nurses, and 250 enlisted personnel.

During the Persian Gulf War, the ships were

given the resources to receive 200 casualties per day

for 30 days. The internal organization of the ship’s

medical treatment facilities and the casualty flow

plan, from the helicopter flight deck through the

treatment areas to the patient wards, was designed

to be simple and rational (Figure 6-14). Although

a hospital ship is a remarkable facility with extraordinary treatment capabilities, medical officers

should remember that like any hospital, it is useful

only if it can be reached by casualties. For the

casualty who requires resuscitative surgery, a hospital ship is useful only if the combat occurs near a

coastline.11
139

Deployable Hospitals

a

b

Fig. 6-14. Casualty flow in the USNS Comfort as it was originally configured prior to its service in the Persian Gulf War;

(a) the arrangement of the main deck of the ship and (b) a cross-section of the ship with arrows indicating the casualty

flow. The most important medical treatment facilities—the casualty receiving area, the operating rooms, and the

intensive care wards—are all amidship on the main deck. This location ensures minimal rocking and rolling in a

seaway and provides maximal protection from enemy action. Reprinted from Auxiliary and Special Mission Ship

Acquisition Project Office. FY 83 Shipbuilding Program. Naval Sea Systems Command, Washington, DC; February 1984.

T-AH 19 Hospital Ship. Diagram: Courtesy of Captain T.G. Patel, Medical Corps, US Navy, Bureau of Medicine and

Surgery, Washington, DC.

Recovery Operating Complex

ICU: Intensive Care Unit

IMCU: Immediate Care Unit

LCU: Light Care Unit

LTCU: Limited Care Unit

Decontamination Elevator

Area

ICU

Casualty Recep.

IMCU

IMCU

IMCU

IMCU

LTCU

LTCU

LCU & LTCU

LTCU

Recovery

Physical

Therapy

Operating Complex

Radiological Casualty Reception

Services Satellite

Laboratory

ICU

Radiological Services

used in the Korean War. During the Vietnam War,

the MUST, an advanced-technology approach, replaced the tented MASH with an environmentally

controlled facility. The MUST’s complexity and

cost detracted from its value. During the 1980s,

DEPMEDS, another advanced-technology approach,

was begun. DEPMEDS was based on an extensive

systems analysis of field medical needs, and a variety of modular hospitals housed in special tents and

metal boxes were fielded. Although DEPMEDS

both improved the level of medical care in deployed

hospitals and simplified equipment procurement,

excessive weight and volume gravely compromised

deployability.

Analysis of afteraction reports from the Persian

Gulf War raised questions regarding the appropriateness of DEPMEDS equipment and the lack of

mobility of deployable hospitals. Owing to the

fluidity of the deployment, and particularly of the

ground offensive itself, deployed hospitals were

frequently required to relocate on short notice.

Distances traveled and the degree of mobility varied widely. Transportation assigned to the unit was

sometimes inadequate. The time required to become fully operational varied from several hours to

2 weeks. All personnel assigned to the hospital

were required to help pack and unpack equipment

for movements. Logistical supply lines were usually able to keep pace with this often-rapid forward

deployment, however, and few chronic shortages

of supplies and equipment were experienced by the

onset of the ground war.

MF2K and MRI are refinements of DEPMEDS.

These systems will decrease the number and types

of hospitals and make it possible to tailor medical

assets by mission. Perhaps the two most important

changes are the deletion of the MASH and its replacement by the FST, and the design of one single

hospital type to replace the present multiple hospital types.
Anesthesia and Perioperative Care of the Combat Casualty

140

REFERENCES

1. Odom CB. Third US Army. In: Carter BN, ed. Activities of Surgical Consultants. Vol 1. In: Coates JB Jr. Surgery in

World War II. Washington DC: US Department of the Army, Medical Department, Office of The Surgeon General;

1962: 315.

2. Brewer LA III, Burford TH. Administrative considerations in the Mediterranean (formerly North African)

Theater of Operations. In: Berry FB, ed. Thoracic Surgery. Vol 1. In: Coates JB Jr, ed. Surgery in World War II.

Washington, DC: US Department of the Army, Medical Department, Office of The Surgeon General; 1963: 129–131.

3. Department of Defense Instruction 6430.1, dated 21 June 1982. Washington, DC: DoD. In: Scotti MJ, chairman.

Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs. Fort Detrick, Frederick,

Md: Defense Medical Standardization Board; 1990: 1.

4. Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs.

Fort Detrick, Frederick, Md: Defense Medical Standardization Board; 1990.

5. Johannigman JA, Putnam AT. Clinical evaluation of the Impact Uni-Vent 750. Milit Med. 1994;159(5):403–408.

6. Perkins DE. Colonel, Medical Corps, US Army. Personal communication, June 1995.

7. US Army Office of The Surgeon General, Professional Services Directorate. Operation Desert Storm: Professional

Afteraction Review. Phoenix, Ariz: US Army Office of The Surgeon General; June–July 1991.

8. Dorsey DA. Military and emergency medicine. Paper prepared for Military Studies 1, Uniformed Services

University of the Health Sciences, Bethesda, Md; 1992.

9. Steinweg KK. Mobile surgical hospital design: Lessons from 5th MASH surgical packages for Operations Desert

Shield/Storm. Milit Med. 1993;158:733–739.

10. Gander TJ. Jane’s NBC Protection Equipment. 5th ed. Surry, United Kingdom: Jane’s Information Group Limited;

1992: 203.

11. Oschner MG, Harviel JD, Stafford PW, et al. Development and organization for casualty management on a 1,000

bed hospital ship in the Persian Gulf. J Trauma. 1993;32:501–513.
Military Anesthesia Machines

141

W. CLAYTON PETTY, M.D.*

Chapter 7

MILITARY ANESTHESIA MACHINES

INTRODUCTION

FIELD ANESTHESIA MACHINE MODEL 885A

Lower Case

Upper Case

Attaching the Medical Gas Supply

Pipeline Circuits

Flowmeters

Vaporizer

Breathing Circuit

Checkout and Maintenance

OHMEDA UNIVERSAL PORTABLE ANESTHESIA CIRCUIT

Specifications and Operation

Checkout and Maintenance

IDEAS FOR FUTURE MILITARY ANESTHESIA MACHINES

SUMMARY

*Captain, Medical Corps, U.S. Navy; formerly, Professor and Vice Chairman, Department of Anesthesiology, Uniformed Services University

of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799; currently, Professor and Chairman, Department of

Anesthesiology, Madigan Army Medical Center, Tacoma, Washington 98431-5000
Anesthesia and Perioperative Care of the Combat Casualty

142

Anesthesia machines designed and manufactured

for the U. S. military have had unique features since

their inception during World War II. Prior to World

War II, physicians, nurses, and dentists usually

administered ether by an open-drop technique,

which consisted of dripping it onto a face mask

covered with two to four thin layers of cotton mesh

(Figure 7-1). Until the Persian Gulf War, anesthesia

machines in the field of combat were very similar to

those used in civilian hospitals in the United States.

During and after World War II, the first militarily

specific anesthesia machines were sold. Chapter 31,

A Brief History of Military Anesthesia, describes

the milestones in the development of anesthesia

machine Models 675 (manufactured by the former

McKesson Appliance Co.), 685A, 685B, and 785

(manufactured by Ohio Chemical and Manufacturing Co., which is now owned by Ohmeda, Inc.,

Madison, Wis.), and the present Field Anesthesia

Machine (FAM) Model 885A (manufactured by

Ohmeda).

One of the major problems in the development of

anesthesia machines for the military has been the

lag time between the concept and the delivery of the

product. Since the Korean War, not one anesthesia

machine designed for civilian use has met the immediate needs of the U. S. military in combat. At the

beginning of the Vietnam War, U.S. military hospitals in Vietnam delivered ether with the “pig” (Ohio

685A) anesthesia machine, which was designed

immediately after World War II and used in the

Korean War. In the Vietnam War, the FAM Model

785 was introduced but was immediately outmoded

because halothane had been introduced while the

785 Model was being developed. The FAM Model

785 had a cyclopropane flowmeter (which rapidly

became obsolete), and a large, in-circuit vaporizer for ether, but was unsafe for the delivery of

halothane. Anesthesia providers overcame this

problem by attaching a halothane single-agent, temperature-compensated vaporizer to the FAM 785;

they buried all the cyclopropane tanks and used

halothane as the major inhalational anesthetic (with

the addition of nitrous oxide) for the remainder of

the war. The FAM Model 885 was developed in the

hiatus between the Vietnam War and the Persian

Gulf War. An additional oxygen flowmeter was

mounted in place of the cyclopropane flowmeter,

and a universal vaporizer replaced the in-circuit

ether vaporizer. A Model 885-Conversion superseded the Model 885 and was eventually replaced

INTRODUCTION

Fig. 7-1. Most anesthetics given during the American

Civil War, World War I, and World War II were administered by dripping ether onto a gauze-covered face mask.

Fig. 7-2. Field Anesthesia Machine (FAM) Model 885A

with an oxygen analyzer. The circle-system machine has

a vaporizer, carbon dioxide absorber, flowmeters, and an

adult patient breathing circuit. Compressed medical gases

are required. Photograph: Permission granted by

Ohmeda, Inc, Madison, Wis.
Military Anesthesia Machines

143

by Model 885A. Hospitals mobilized for Operation

Desert Shield (the build-up phase of the Persian

Gulf War) were initially supplied with the FAM

Model 885A and later with the Ohmeda Universal

Portable Anesthesia Circuit (PAC) (Figures 7-2 and

7-3). Military anesthesia providers (especially those

who were members of the reserves) realized that

both anesthesia machines were not compatible with

the techniques and standards of practice used in

civilian and military hospitals in the United States.

Most of the anesthesia providers in Operation Desert

Storm (the fighting phase of the Persian Gulf War)

considered the FAM and the PAC to be of historical

importance only. Training with the machines was

extremely limited, and the majority of anesthesia

providers had been exposed only superficially to

the principles of operation of a universal vaporizer.

Many were hesitant to use the FAM and the PAC

because they were unfamiliar with the machines

and they were genuinely concerned about the standard of care and medicoliability issues.

Military anesthesia providers require a small,

lightweight, versatile, easily transportable anesthesia machine for use in a frontline aid station and

in a rear, full-service field hospital. Historically,

anesthesia providers in the United States have

leaned heavily toward circle breathing systems;

thus, this was a major determining factor in the

development of anesthesia machines for the military. Two anesthesia machines are stocked by the

Department of Defense’s Deployable Medical Systems (DEPMEDS): the FAM and the PAC. The FAM

is geared for use in field hospitals and in conflicts

lasting longer than 2 weeks. The PAC fits inside a

Fig. 7-3. Ohmeda Portable Anesthesia Circuit (PAC). A

draw-over vaporizer is the heart of this nonrebreathing

lightweight anesthesia machine. Photograph: Permission granted by Ohmeda, Inc, Madison, Wis.

briefcase and is suitable for use in the battalion aid

station and for fast-in and fast-out conflicts. Our

discussion will focus on detailed descriptions of

the FAM Model 885A and the PAC, and on concepts that might influence evolutionary changes

for a new FAM.

FIELD ANESTHESIA MACHINE MODEL 885A

be pushed in to relieve the pressure inside the case

before the lower and upper cases can be separated.

Releasing four drawbolt fasteners separates the container into upper and lower cases (Figures 7-6 and 7-7).

Lower Case

The lower case contains the anesthesia machine,

accessories, and spare parts (Exhibit 7-1). As the

absorber head is pulled upward, the support arms

are held in vertical position by a spring-loaded snap

bar at the base. A hinged thumb bolt is tightened

into a slot on one support arm to keep the absorber

head vertical (Figures 7-8 and 7-9). Between the two

support arms are an open and a latched compartment (Figure 7-10). The open compartment has

spring holders that secure adult- and child-sized

Military anesthesia providers should familiarize

themselves with the manufacturer’s Instruction and

Service Manual With Illustrated Parts List,

1 on which

much of the following information is based. A

distinctive carrying container, 13 in. wide x 20 in.

long x 18 in. high, holds the entire FAM (Figure 7-4).

All that is needed to put the machine into service is

a cylinder of oxygen, carbon dioxide–absorbent

granules, and a bottle of liquid anesthetic agent.

The FAM and its container have a combined weight

of 115 lb and can be lifted by grasping two handles

on the lower case. During shipment, four glides are

inserted into sprockets on the bottom of the container and these glides are replaced with four casters when the machine is assembled (Figure 7-5).

A pressure-release valve keeps dust from entering the container. The pressure-relief device must
Anesthesia and Perioperative Care of the Combat Casualty

144

a b

Fig. 7-5. Four glides (a) are placed in sprockets on the

bottom of the lower case for shipment and storage. Four

casters (b), stored inside the bottom case, replace the

glides when the Field Anesthesia Machine Model (FAM)

885A is in use. Redrawn with permission from Ohmeda,

Inc, Madison, Wis.

a

Fig. 7-6. A pressure-release valve keeps dust and other

materials from entering the case. Prior to opening the

case, the center button (a, front view) is pushed to return

pressure within the case to atmospheric conditions. A

groove (b, side view) fits in a hole cut in the case wall and

a flat bolt secures the device from the inside. Redrawn

with permission from Ohmeda, Inc, Madison, Wis.

Fig. 7-7. Field Anesthesia Machine (FAM) Model 885A

carrying case, opened. Bottom case (left) showing the

FAM canister and rear of the flowmeter manifold. Upper

case (right) with the medical gas hoses, a clipboard, and

compressed gas regulators (one at each corner).

Fig. 7-4. Carrying case for the Field Anesthesia Machine

(FAM) Model 885A. The upper and lower cases are held

together by two drawbolts on each side of the case.

Shipping glides have been replaced by four casters. Note

one of the carrying handles on the end of the case.

b
Military Anesthesia Machines

145

EXHIBIT 7-1

ITEMS IN LOWER CASE, FIELD

ANESTHESIA MACHINE MODEL 885A

15⁄16- and 11⁄8-in. open-end wrench

7⁄8- and 3⁄4

–

in. open-end wrench

Tee-valve wrench

Flow calculator

3⁄16-in. hex Allen wrench

Y-inhaler

Mask elbow

Large and medium adult masks

Child and infant masks

Extra check valve disks

Extra cylinder gaskets

Extra funnel plug with chain

Four wheels

Large cylinder adapters for oxygen and nitrous

oxide

Protective closure devices for cylinder adapters

Extra absorber gaskets

Instrument tray

Cylinder holder

Gas evacuation tubing

19-mm connector

Instrument tray with oxygen monitor case

Oxygen sensor tee, probe, and cable

Sight level

Adapted with permission from Ohmeda, Inc. Instruction

and Service Manual With Illustrated Parts List. Model 885A.

Anesthesia Apparatus, Gas, Nitrous Oxide, Oxygen and

Volatile Liquid Anesthetics, Portable 4-Cylinder Capacity.

Ohmeda, Madison, Wis: 1990: 14.

Fig. 7-8. Field Anesthesia Machine (FAM) Model 885A in

the upright position. Side arms support the vaporizer

and flowmeter manifold. One end of the utility tray is

supported by a brace connected to the support arms. A

line level on the inside of the support arm is used to level

the machine prior to use. Casters have replaced the shipping glides. A gas-specific noninterchangeable male

Schrader valve is attached to the female outlet of the pinindexed reducing valve on the compressed oxygen cylinder. The opposite end of the oxygen hose has a female

Schrader valve that is attached to the male oxygen inlet of

the FAM. A carrying handle, two drawbolts, and the pressure-relief valve can be seen. A spring-latched bar (not

seen) secures the bottom end of the support arms. Redrawn

with permission from Ohmeda, Inc, Madison, Wis.

masks. Adjacent to the masks, in FAM models

with an oxygen monitor, is an unsecured box containing the oxygen sensor cartridge. The latched

compartment contains the elbow connector, the

Y-connector for the breathing circuit, a box with

three vials of extra parts, and the tee-valve wrench

(which is used to turn the E-cylinder to the ON

position). Replacement parts in the three vials

include vaporizer replacement parts, cylinder yoke

gaskets, and disks for the inhalation and exhalation

check valves. If the FAM has an oxygen monitor,

the cable assembly and sensor tee will be stored in

the box.

Corrugated scavenger hoses are stored inside the

absorber chamber. Lifting the absorber head reveals the utility tray, which is held in place by a

hook-and-loop strap and four casters snapped into

spring holders (Figure 7-11). The front end of the

tray has two round brackets that slide onto two

mounting studs behind the flowmeter manifold

(Figure 7-12). A tray brace is permanently attached

to the top of the support arms and fits snugly
Anesthesia and Perioperative Care of the Combat Casualty

146

Fig. 7-9. Field Anesthesia Machine (FAM) Model 885A. A

hinged thumb bolt secures the absorber head in the vertical

position. Photograph: Printed with permission from

Ohmeda, Inc, Madison, Wis.

Fig. 7-11. Field Anesthesia Machine (FAM) Model 885A.

After the absorber head is in the vertical position, the utility

tray, casters, and mounts for the oxygen and nitrous oxide

H-cylinder adapter can be seen. Spring-loaded clamps in the

end of the case secure either the casters or glides. A strap holds

the utility tray in place. Redrawn with permission from

Ohmeda, Inc, Madison, Wis.

on the side of the metabolic oxygen flowmeter (Figure 7-13). During assembly, the set screw is loosened and the bracket is moved parallel to the

flowmeter manifold, and the oxygen monitor is

then mounted to the bracket. The oxygen sensor

probe is inserted in the sensor tee placed between

against the edge of the support arms when not in

use. The tray brace slides into two brackets on the

underside of the utility tray to support the opposite

end of the tray (see Figure 7-8).

The mounting bracket for the oxygen monitor is

attached by a set screw to the utility mounting stud

Fig. 7-10. Field Anesthesia Machine (FAM) Model

885A. The space between the support arms contains two compartments. An open compartment

has two posts holding oronasal masks. A lid

(shown removed) for the closed compartment

protects the Y breathing-circuit connector, the

elbow adapter, spare parts containers, and the

tee valve wrench for E-cylinders. Models with

an oxygen sensor have the sensor cartridge stored

next to the masks and the sensing cable and sensing tee inside the closed compartment. Redrawn

with permission from Ohmeda, Inc, Madison, Wis.
Military Anesthesia Machines

147

Fig. 7-14. Field Anesthesia Machine (FAM) Model 885A.

The oxygen monitor is mounted to the bracket of the absorber head. A sensor cable connects the oxygen sensor in

the sensor tee of the fresh-gas outlet of the breathing circuit

to the monitor. The inspiratory limb of the breathing circuit

will be attached to the open end of the sensor tee. Photograph: Printed with permission from Ohmeda, Inc, Madison, Wis.

Fig. 7-13. Field Anesthesia Machine

(FAM) Model 885A. The oxygen

mounting bracket is attached to one

of the utility mounting studs during

shipment (left). Releasing the set

screw allows the bracket to be moved

approximately 180°. The oxygen

monitor is mounted on the bolt pictured at the end of the bracket (right).

Redrawn with permission from

Ohmeda, Inc, Madison, Wis.

Fig. 7-12. Field Anesthesia Machine (FAM) Model 885A.

Rear view of the absorber head. Two mounting studs hold

one end of the utility tray. Inlet male noninterchangeable

Schrader connectors for oxygen and nitrous oxide are shown.

The nitrous oxide pressure-sensor shutoff valve blocks the

flow of nitrous oxide to the flowmeter when the pressure of

oxygen in the pipeline is less than 20 psig. Reprinted with

permission from Ohmeda, Inc, Madison, Wis.
Anesthesia and Perioperative Care of the Combat Casualty

148

Fig. 7-15. Field Anesthesia Machine (FAM) Model 885A,

large-cylinder adapter. An American National Standards

Institute (ANSI) nut-and-gland medical gas–coded thread

attaches to a matching threaded cylinder outlet. The

opposite end of the adapter has a pin-index safety system

(PISS) that is gas-specific (a PISS regulator is attached to

the PISS fitting). Redrawn with permission from Ohmeda,

Inc, Madison, Wis.

Fig. 7-17. Field Anesthesia Machine (FAM) Model 885A. Two

wrenches for connecting cylinder

adapters are mounted on the inside of one support arm. Redrawn

with permission from Ohmeda,

Inc, Madison, Wis.

the common gas outlet and the inspiratory limb of

the patient breathing circuit (Figure 7-14).

Large cylinder connectors for oxygen and nitrous oxide are stored on threaded mounts (see

Figure 7-11) adjacent to the end of the utility tray.

These connectors attach to cylinders, which do

not have the pin index safety system (PISS) holes

drilled in the cylinder valve. An American National

Standards Institute (ANSI) nut-and-gland medicalgas–coded thread of the connector attaches to

the threaded cylinder outlet; the other end of the

connector has the appropriate PISS for the gasspecific cylinder regulator gauge (Figure 7-15). Beneath the utility tray is a four-holed cylinder holder

that mounts on the top of the lower case and keeps

the E-cylinders in place during use (Figure 7-16).

Mounted on one side of the lower case wall is the

flow calculator, which is used to determine anesthetic concentrations delivered by the universal

vaporizer.

On the inside of one support arm are extra

absorber gaskets and a small sight level for leveling the machine during assembly (see Figure 7-8). On

the inside of the other support arm are two openend wrenches, which are used for connecting connectors to cylinders, and for other purposes (Figure 7-17).

Upper Case

Additional equipment and accessories for assembling the completed anesthesia machine are

contained in the upper case (Exhibit 7-2). Figure 7-18

shows the fastener holding the clipboard in place.

A compartment secured by a fastener is on each end

of the upper case. When the clipboard is removed

and the compartments are opened, the rebreathing bags, head harness, oxygen and nitrous oxide

PISS regulators, long and short gas-supply hoses,

corrugated breathing tubes, and equipment for a

pediatric nonrebreathing system are revealed (Figure 7-19).

Fig. 7-16. Field Anesthesia Machine (FAM) Model 885A.

After the utility tray is removed, the four-holed cylinder

holder can be taken out and fitted to the cylinder seat on

top of the lower case to help secure the E-cylinders in the

upright position. The weight of the cylinders contributes

to the stability of the FAM. Redrawn with permission

from Ohmeda, Inc, Madison, Wis.
Military Anesthesia Machines

149

Long and short gas-supply hoses for oxygen and

nitrous oxide

Regulator assemblies for oxygen and nitrous

oxide

Head strap

Long and short corrugated breathing tubes

Clipboard

Pediatric supply hose

1-L Breathing bag with scavenging valve

3-L Breathing bag

Adapted with permission from Ohmeda, Inc. Instruction

and Service Manual With Illustrated Parts List. Model 885A.

Anesthesia Apparatus, Gas, Nitrous Oxide, Oxygen and

Volatile Liquid Anesthetics, Portable 4-Cylinder Capacity.

Ohmeda, Madison, Wis: 1990: 14.

EXHIBIT 7-2

ITEMS IN UPPER CASE, FIELD

ANESTHESIA MACHINE MODEL 885A

Fig. 7-19. Field Anesthesia Machine

(FAM) Model 885A. Breathing tubes,

a head harness, rebreathing bags, a

pediatric nonrebreathing circuit, and

gas hoses are stored beneath the clipboard in the upper case. A pin index

safety system (PISS) gas regulator is

secured at each corner of the case.

Redrawn with permission from

Ohmeda, Inc, Madison, Wis.

Attaching the Medical Gas Supply

Cylinders containing oxygen and nitrous oxide

are connected to the anesthesia machine by using

the PISS regulator for E-cylinders or the large-cylinder PISS adapters. E- or D-cylinders will fit inside

the four-holed holder in the lower case (see Figures

7-8 and 7-16). It is important to briefly review the

differences in physical characteristics between the

storage and the delivery of oxygen and nitrous

oxide. E-cylinders (internal volume 4.8 L) at 21.1°C

(70°F) contain either 660 L of compressed oxygen at

a pressure of 1,900 psig or 2.92 kg of liquid nitrous

oxide (which evaporates to provide 1,590 L) at a

pressure of 750 psig.2 Oxygen boils at –183.0°C at 1

atm and has a critical temperature (ie, the temperature above which a substance cannot be liquefied

regardless of the pressure applied) of –118.6°C.3

Oxygen can only be stored as a gas at room temperature, and the amount of oxygen in the cylinder is

proportional to the cylinder pressure (Figure 7-20).

Nitrous oxide at room temperature is below its critical

temperature and is stored as a liquid under pressure

Fig. 7-18. Field Anesthesia Machine

(FAM) Model 885A. Upper case. A

fastener is holding the clipboard in

place. Fastened compartments are

shown at opposite ends of the case.

Redrawn with permission from Ohmeda, Inc, Madison, Wis.
Anesthesia and Perioperative Care of the Combat Casualty

150

Fig. 7-21. The pin index safety system (PISS), which is

designed for medical gases compressed in cylinders.

Each medical gas is assigned two holes of the six-holed

main index (upper figure). Oxygen is assigned positions

2 and 5 and nitrous oxide positions 3 and 5. Above the

two holes is the cylinder-gas outlet.

in the cylinder. The content of the nitrous oxide

cylinder is not proportional to the cylinder pressure

until the liquid nitrous oxide has completely evaporated.

An E-cylinder valve in the United States must

comply with the PISS. Three holes are drilled in

the cylinder valve: one is the gas outlet and the

other two are limited-depth holes that are positioned to correspond with the assigned PISS for

oxygen (numbers 2 and 5) or nitrous oxide (numbers 3 and 5) (Figure 7-21). Both FAM oxygen and

nitrous oxide regulators have two pins that mate

with the paired holes in the cylinder valve (Figure

7-22). The oxygen regulator is marked with the

chemical symbol O2 and is painted white (the international color code for oxygen) on the pressure

gauge dial face and the tee-securement handle. The

nitrous oxide regulator is marked with the chemical

symbol N2O and painted blue (the international

color code for nitrous oxide) on the pressure gauge

dial face and the tee-securement handle. After a

regulator is attached to either an E-cylinder valve or

a large-cylinder PISS connector, a male Schrader

noninterchangeable connector (Figure 7-23) on the

Fig. 7-20. Oxygen and nitrous oxide compressed-gas cylinders.

Oxygen (green) is stored as a compressed gas because it is above its

critical temperature at room temperature. The amount of oxygen in

the cylinder is proportional to the cylinder pressure. Nitrous oxide

(blue) is stored as a liquid under pressure. As the tank empties, the

amount of nitrous oxide in the cylinder is not proportional to the

pressure in the cylinder. When the last drop of liquid nitrous oxide

is evaporated, the cylinder contains only gas, and then the amount

of nitrous oxide in the cylinder is proportional to the amount of

gaseous nitrous oxide. Photograph: Printed with permission granted

by Medical Systems Division, Ohmeda, Inc, Madison, Wis.
Military Anesthesia Machines

151

Fig. 7-23. Schrader noninterchangeable connectors at the

ends of the gas hoses. Each medical gas has a specific

connector assigned to avoid cross-connection of gases. One

end of the gas hose has a male connector (left) that fits the

gas-specific female connector (right) on the pin index safety

system (PISS) regulator, and the other end has a female

connector that fits the male inlet connection on the Field

Anesthesia Machine (FAM) Model 885A. Schrader adapters allow rapid connections and disconnections without

the use of special tools. Photograph: Printed with permission of Ohmeda, Inc, Madison, Wis.

medical gas–supply hose is inserted into the gasspecific female Schrader connector on the regulator. Gas-supply hoses come in two lengths, 114 and

40 in. A color-coded identification disk is found on

each end of the supply hose. The female Schrader

connection on the opposite end of the medical gas–

supply hose is then connected to the male Schrader

inlet connector on the control head. Figure 7-8

shows the connection of an E-cylinder containing

oxygen to the FAM.

Cylinders larger than E-cylinders are sometimes

supplied to combat hospitals to improve the efficiency of the medical gas supply (Figures 7-24 and

7-25). A large cylinder connector (see Figure 7-15),

which is nut-and-gland coded for either oxygen or

nitrous oxide, is attached to the threaded cylinder

outlet, and a PISS oxygen or nitrous oxide regulator

is attached to the PISS-connector outlet.

When an oxygen-powered ventilator is required,

it is necessary to use either (a) the second oxygen

regulator, attached to an E-cylinder or large-cylinder connector, or (b) an oxygen regulator equipped

with two male Schrader connectors (Figure 7-26).

Pipeline Circuits

Gases from the oxygen and nitrous oxide cylinders enter the FAM through the two male Schrader

noninterchangeable inlets on the rear of the control

head (see Figure 7-12). Before the gases enter the

FAM circuit, the regulator has reduced the pressure

to approximately 40 psig. Nitrous oxide must flow

through the pressure-sensor shutoff valve before it

can enter the nitrous oxide flowmeter (see Figure 7-

12 and Figures 7-27 and 7-28). The pressure-sensor

shutoff valve will block the flow of nitrous oxide to

the flowmeter if the oxygen pressure on its diaphragm is less than 20 psig.

Oxygen is distributed to four areas after it enters

the FAM: (1) the metabolic oxygen flowmeter control valve, (2) the diaphragm of the nitrous

oxide pressure-sensor shutoff valve, (3) the oxygen

Fig. 7-22. Oxygen regulator. Two pins are positioned to fit the

2,5 pin index safety system (PISS) of the oxygen cylinder valve.

The handle is painted white (international color assigned to

oxygen) and is labeled with the chemical symbol for oxygen.

A pressure gauge reflects the cylinder pressure in psig and

kg/cm2, is painted white, and labeled O2. A male Schrader

noninterchangable connector can be seen at the bottom of the

regulator. Redrawn with permission from Ohmeda, Inc, Madison,

Wis.
Anesthesia and Perioperative Care of the Combat Casualty

152

Fig. 7-25. Anesthesia equipment at the 12th Evacuation

Hospital in Saudi Arabia during the Persian Gulf War.

Patient monitors, a Field Anesthesia Machine (FAM) Model

885A with an oxygen monitor, a ventilator, and a blood

warmer are shown. The rebreathing bag is attached to a

switch-over valve that simplifies the adaptation of the ventilator to the breathing circuit. Against the wall (left) are two

H-cylinders of compressed oxygen. These cylinders are

painted two colors: green (US designation for oxygen) and

white (international color assigned to oxygen), and are

stamped OXYGEN in white letters on the green section of

the cylinder. One oxygen H-cylinder is being used to power

the ventilator, and the adapter and pin index safety system

(PISS) regulator provided with the FAM are not being used.

Nonstandard breathing tubes are connected to the FAM.

Photograph: Courtesy of Captain D J Rutkowski, CRNA, US

Army Nurse Corps.

Fig. 7-26. A pin index safety system (PISS) oxygen regulator

fitted with two Schrader couplers. One supplies oxygen to the

Field Anesthesia Machine (FAM) Model 885A, and the other is

a power outlet for the ventilator. Redrawn with permission

from Ohmeda, Inc, Madison, Wis.

Fig. 7-24. Field Anesthesia Machine (FAM)

Model 885A at the 93rd Evacuation

Hospital, Rafha, Saudi Arabia, during

the Persian Gulf War. Two operations

are under way in the same operating

room. The FAM can be seen on the right.

Photograph: Courtesy of Captain DJ

Rutkowski, CRNA, US Army Nurse

Corps.

Schrader

coupler

Pressure gauge
Military Anesthesia Machines

153

Fig. 7-27. Field Anesthesia Machine (FAM) Model 885A pipeline schematic for oxygen and nitrous oxide. Oxygen from

the compressed medical oxygen cylinder (1) is reduced (3) to a pressure of 40 psig (5) before entering the FAM. Oxygen

is distributed to metabolic oxygen flowmeter control valve (8), diaphragm of the nitrous oxide pressure sensor shutoff

valve (7), oxygen flush valve (15), and the oxygen-for-vaporizer flowmeter control valve (12). Nitrous oxide in

cylinders (2) is reduced (4) to 40 psig (6) before it enters the FAM. Nitrous oxide passes through the nitrous oxide

pressure-sensor shutoff valve (7) to the nitrous oxide flowmeter control valve (10). Metabolic oxygen (9) and nitrous

oxide (11) mix in a common pipeline and then combine with the oxygen-for-vaporizer (13, 14) and anesthetic agent

emitting from the vaporizer (16). Mixed gases are carried by the inspiration limb of the breathing circuit to the Y piece

(19) and then to the patient. Exhaled gases enter the expiratory limb and flow through the exhalation check valve (20),

some of the gases go into the rebreathing bag (21), and some exit through the adjustable pressure-limiting valve (22),

if it is open, into the scavenging system; the remaining gases pass through the carbon dioxide absorber (23), through

the inspiration check valve (24), and begin the cycle again. A pressure gauge (17) monitors breathing-circuit pressure.

An emergency nonadjustable pressure-relief valve (18) releases gases into the atmosphere when the circuit pressure

exceeds 60 to 80 mmHg. Photograph: Printed with permission from Ohmeda, Inc, Madison, Wis.

a b

Fig. 7-28. This diagram shows how the nitrous oxide pressure-sensor shutoff valve works. (a) When the oxygen line pressure

exceeds 25 psig, a large diaphragm counteracts the force applied by a valve-return spring on the valve. In this position,

nitrous oxide flows through the shutoff valve. (b) Oxygen pressure drops below 25 psig and the valve-return spring forces

the valve to seat, closing the shutoff orifice. Nitrous oxide still flows to the pressure-sensor shutoff valve but cannot flow

through the valve to the nitrous oxide flowmeter. Photograph: Printed with permission granted by Medical Systems

Division, Ohmeda, Inc, Madison, Wis.
Anesthesia and Perioperative Care of the Combat Casualty

154

Fig. 7-29. Top of the flowmeter manifold, showing the

assigned numbers imprinted for each medical gas. The

numbers above the bolt holding the flow tube in place

must match the number on the bottom of the flow tube.

From the left, number 2 is for nitrous oxide, 4 is for lowflow oxygen-for-vaporizer, 5 is for high-flow oxygenfor-vaporizer, and 1 is for metabolic oxygen. Switching

flow tubes can be disastrous because the output of the

flowmeter is determined by the specific viscosity and

density of the medical gas flowing through the flow tube.

flush valve, and (4) the oxygen-for-vaporizer

flowmeter.

Flowmeters

Flowmeters are provided for metabolic oxygen,

oxygen for the vaporizer, and nitrous oxide. The

range for the flowmeters is, for metabolic oxygen,

200 mL/min to 7 L/min; for low-flow oxygen for

the vaporizer, 20 to 180 mL/min; for high-flow

oxygen for the vaporizer, 100 mL/min to 1 L/min;

and for nitrous oxide, 200 mL/min to 8 L/min.

Accuracy for all flowmeters is ±20% up to flows of

1,000 mL/min; above flows of 1,000 mL/min, the

accuracy is ±10% (eg, at a setting of 5 L/min, the

output would be 4.5–5.5 L/min). Each flowmeter

tube, float, and scale are a matched set and must be

replaced as a unit. Each flow tube is gas-specific,

and a numbering system on the flowmeter manifold

and each matching flow tube enhances the correct

placement of the flow tubes if they are removed for

maintenance or replacement. Numbers on the top

of the flowmeter manifold are placed above the bolt

that holds the flowmeter in place (Figure 7-29).

Metabolic oxygen is number 1; oxygen-for-vaporizer, high flow, is 5; oxygen-for-vaporizer, low flow,

is 4; and nitrous oxide is 2. The corresponding

number is printed on the bottom of the flow tube.

Switching flow tubes can be disastrous. One of the

two documented deaths attributed to the FAM occurred when someone switched the nitrous oxide

flow tube with the high-flow oxygen-for-vaporizer

flow tube.4 This switch resulted in a delivery of

6.2% isoflurane instead of the expected 1.5% setting, and the overdosing and eventual death of the

patient.

Flowmeter scales and control knobs are color

coded: metabolic oxygen is white, oxygen-for-vaFig. 7-31. Nitrous oxide and oxygen-for-vaporizer

flowmeter control knobs and flow tubes. Nitrous oxide is

labeled N2O and is painted blue (international and US

color assigned to nitrous oxide). The nitrous oxide–flowtube scale is labeled N2O, ranges from 0.2 to 8 L/min, is

painted blue, and is protected by a plastic shield. The

oxygen-for-vaporizer control knob is painted yellow

(manufacturer’s choice), and is labeled O2 FOR VAPORIZER. The single oxygen-for-vaporizer flowmeter control knob meters both low- and high-flow oxygen. The

flow-tube scales are labeled O2, painted yellow, and

protected by a plastic shield; the low-flow tube ranges

from 20 to 180 cc/min, and the high-flow tube ranges

from 100 to 1,000 cc/min. The nitrous oxide pressuresensor shutoff valve can be seen below the nitrous oxide

flowmeter housing.

Fig. 7-30. The metabolic oxygen flowmeter control knob

is fluted, labeled O2, painted white (international color

assigned to oxygen), and is positioned on the far right.

The flow-tube scale is labeled O2, ranges from 0.2 to 7 L/

min, is also white, and is protected by a plastic shield. The

adjustable pressure-limiting (pop-off) valve can be seen,

with the proximal end of the scavenger hose attached.
Military Anesthesia Machines

155

Liquid-agent

temperature gauge

Universal filling port

porizer is yellow, and nitrous oxide is blue (Figures ON/OFF control

7-30 and 7-31). Flowmeters and scales are protected by a transparent plastic shield. Metabolic oxygen and nitrous oxide flow into a common pipeline circuit at the top of the flowmeter manifold.

The high and low flowmeters for oxygen-for-vaporizer are controlled by a single knob. The flow first

enters the bottom of the low-flow tube, exits the top

and enters the bottom of the high-flow tube, and

finally exits the top of the high-flow tube to enter

the common gas pipeline (Figure 7-32). Oxygenfor-vaporizer bubbles through the anesthetic liquid and carries anesthetic vapor into the common

gas outlet if the vaporizer control dial is in the ON

position; otherwise, the oxygen bypasses the vaporizer and enters directly into the common gas outlet.

The metabolic oxygen flowmeter control knob is

fluted (see Figure 7-30) to enhance identification.

Vaporizer

The FAM 250 mL vaporizer will deliver accurate,

metered concentrations of isoflurane, halothane,

Sight level opening

Fig. 7-33. Field Anesthesia Machine (FAM) Model 885A

vaporizer, showing the ON/OFF control, the sight level

opening, the universal filling port, the liquid-agent temperature gauge, the drain spigot, and the common gasoutlet port.

enflurane, ether, and chloroform (Figure 7-33).

Desflurane cannot be used in the vaporizer because

of its unique vapor pressure. The vaporizer is a

brass container filled with a liquid anesthetic. Brass

is a reasonably priced metal with acceptable thermal conductivity and specific heat characteristics.

A dedicated oxygen-for-vaporizer flowmeter

bubbles oxygen through the liquid in the vaporizer

when the ON/OFF control is in the ON position.

Agent output is determined by the same principles

that govern the copper kettle (Figure 7-34). Each

bubble of oxygen is saturated with the vapor of the

liquid anesthetic. The large surface area of the

oxygen bubble allows ample time for the liquid

anesthetic agent to evaporate inside the bubble and

to fully saturate the oxygen flowing through the

vaporizer. Eventually, the oxygen entering the

liquid anesthetic plus the anesthetic vapor exit the

top of the vaporizer and are diluted by the metabolic oxygen and nitrous oxide in the common gas

outlet. At least 50 mL of anesthetic liquid must be

in the vaporizer for the anesthesia provider to be

certain that the desired vapor concentration is

delivered.

Many formulas can be used to calculate the final

output of anesthetic agent concentration in the inspiratory limb of the breathing circuit. ApproxiFig. 7-32. The single-control flowmeter knob controls

flow through the low- and high-flow tubes. Oxygen flow

rate is metered by the position of the control knob in the

cone-shaped orifice. Oxygen passes into the low-flow

tube, causing the float to rise. Increasing the flow of

oxygen causes the float in the low-flow tube to stay at the

top, as oxygen passes into the high-flow tube and begins

to lift the float in the high-flow tube. All oxygen eventually exits from the top of the high-flow tube on its way to

the vaporizer. Photograph: Reprinted with permission

from Schreiber P. Safety Guidelines for Anesthesia Systems.

Telford, Pa: North American Dräger; 1985: 17.

Drain spigot
Anesthesia and Perioperative Care of the Combat Casualty

156

mate calculations of output are accurate enough for

clinical application, of which the following is one

method5:

• Derivation:

VF [mL/min] • [Pa /{Pb – Pa}] • 100

TF [L/min] • 1,000

where % represents the percentage concentration of

anesthetic in the inspiratory limb of the breathing

circuit, VF represents the flow of oxygen through

the vaporizer (in mL/min), TF represents the total

gas flow (in L/min), Pa represents the vapor pressure of volatile agent (in mm Hg), and Pb represents

barometric pressure (in mm Hg).

• Simplification:

° Vapor pressure of halothane is 243 mm

Hg at 20°C and 760 mm Hg barometric

pressure

° Therefore, by substitution:

VF • [243/{760 – 243}] • 100

TF • 1,000

 0.47 VF 0.5 VF

10 TF 10 TF

° Therefore, VF ~ TF • 20 • %.

• Practical applications:

1. An induction concentration of 3% halothane is desired.

Temperature 20°C, barometric pressure

760 mm Hg, fresh-gas flow of 5 L/min:

VF ~ 5 • 20 • 3%

VF = 300 mL/min

° Set vaporizer control to the ON position.

° Set metabolic oxygen and nitrous oxide flowmeters to deliver a combined

flow of 5 L/min.

° Set oxygen-for-vaporizer flowmeter at

300 mL/min.

2. To obtain a maintenance of 1% halothane

in the inspiratory limb of the breathing

circuit at 20°C, barometric pressure of 760

mm Hg, and a fresh-gas flow of 2 L/min:

VF ~ 2 • 20 • 1%

VF = 40 mL/min

° Leave vaporizer control at ON position.

° Set metabolic oxygen and nitrous oxide

flowmeters to give a combined flow of

2 L/min.

° Set oxygen-for-vaporizer flowmeter at

40 mL/min.

To simplify the calculation of vaporizer output

concentration, a Verni-Trol (manufactured by

Ohmeda, Inc., Madison, Wis.) anesthetic vaporizerflow calculator is included in the lower case of the

FAM (Figure 7-35). This calculator is a miniature

slide rule designed for one task: to determine the

final concentration of anesthetic agent in the inspiratory limb of the breathing circuit. The anesthesia provider first finds the desired concentration of

the anesthetic agent vapor on the outermost scale of

the calculator (labeled % CONCENTRATION). Then

the desired total flow rate on the TOTAL FLOW

scale is aligned with the anesthetic agent concentration value. Set the hairline LIQUID TEMPERATURE scale value for the agent in the vaporizer to

correspond to the temperature of the liquid in the

vaporizer. Finally, read the required oxygen-forvaporizer flowmeter setting where the hairline

crosses the Flow Thru Verni-Trol scale. These steps

are illustrated in the following example:

Fig. 7-34. Copper kettle bubble-through vaporizer. Output is determined by the temperature of the liquid anesthetic, the vapor pressure of the liquid anesthetic, the rate

of oxygen bubbling through the liquid, and the barometric pressure. The Field Anesthesia Machine (FAM) Model

885A is a bubble-through vaporizer that can accept the

majority of inhalational anesthetic agents. Photograph:

Reprinted with permission from Morris LE. A new vaporizer for liquid anesthetic agents. Anesthesiology.

1952;13:587.

% =

% =

% = % ~ or
Military Anesthesia Machines

157

1. The desired total flow rate is 5 L/min.

• Desired concentration of halothaneis 1%.

• Vaporizer thermometer reading is 25°C.

2. Find 1% on the CONCENTRATION scale.

• Align 5 L/min value on the TOTAL

FLOW scale with the 1% value.

• Find 25°C on the halothane LIQUID

TEMPERATURE scale and set the hairline.

• The hairline will cross Flow Thru VerniTrol scale at 100 mL/min value.

3. Set metabolic oxygen and nitrous oxide

flowmeters to give a combined 5 L/min

flow.

• Set vaporizer control on vaporizer to

the ON position.

• Set oxygen-for-vaporizer flowmeter at

100 mL/min.

Temperature has a profound effect on vapor pressure and must always be factored in when using the

vaporizer in field conditions. Total flow rates have

major effects on concentration. During induction,

high flow rates are used; when switching to lower

flows for maintenance, the anesthesia provider must

recalculate the flow required through the vaporizer

for maintenance levels of anesthetic.

Most anesthesia providers are not familiar with

the calculations or the Verni-Trol calculator because single-agent temperature- and pressure-compensated vaporizers have replaced Verni-Trol–type

vaporizers. During the Persian Gulf War, many

anesthesia providers believed that the FAM Model

885 vaporizer was outmoded, dangerous, and

should have been replaced immediately. Not many

took the time to learn the technology of a past era,

and only a few felt comfortable administering an

anesthetic with the FAM. A new anesthesia machine for the field will have agent-specific vaporizers available for at least halothane and isoflurane.

A common funnel port is provided on the side of

the vaporizer with a liquid level sight tube. Under

the vaporizer are found a drain, a spigot, and a plug

(see Figure 7-33). The manufacturer recommends

rinsing the vaporizer, first with hot water and then

with ethyl alcohol, after one agent has been drained

and a different agent is to be added. Gas from the

metabolic oxygen and nitrous oxide flowmeters

mix prior to entering the vaporizer housing and do

not enter the vaporizer at any time. The oxygen

from the oxygen-for-vaporizer flowmeter bubbles

through the liquid anesthetic, and both the oxygen

and anesthetic vapor mix with the metabolic oxyFig. 7-35. The Ohio Verni-Trol anesthetic vaporizer-flow

calculator is attached to the inside of the wall of the bottom

case of the Field Anesthesia Machine (FAM) Model 885A.

The calculator is positioned to calculate the parameters to

deliver approximately 1.3% halothane to the breathing

circuit at a liquid anesthetic temperature of 20°C, a barometric pressure of 760 mm Hg, an oxygen-for-vaporizer

flowmeter setting of 150 cc/min, and a metabolic oxygen flowmeter setting of 5 L/min. Find the bar for

HALOTHANE; note that the center of the hairline crosses

the 20°C mark (all agent markings are in °C) and that the

outer end of the hairline crosses the 150 cc/min mark. Next,

read the desired concentration (1.3%, in this case) and the

total flow immediately below the concentration ( 5 L/min).

At the same setting, you could give 1% halothane by increasing the total flow to 6.5 L/min or 3% halothane by

decreasing the total flow to 2.2 L/min. If you wanted to

induce anesthesia in a patient, using 3% halothane at a total

flow of 5 L/min and the halothane in the vaporizer was at

a temperature of 20°C (barometric pressure 760 mm Hg),

you would have to set the oxygen-for-vaporizer flow rate to

320 cc/min. Instructions for use are printed on the calculator. The accuracy of output is reasonable for clinical anesthesia. Remember: each time the metabolic oxygen flows

change (eg, induction to maintenance) or the anesthetic

liquid temperature changes, an adjustment must be made

in the flow rate of oxygen through the vaporizer.
Anesthesia and Perioperative Care of the Combat Casualty

158

knob is tightened excessively, the chamber wall can

be warped, causing leaks. An absorber drain plug

is located on the bottom of the unit.

Carbon dioxide–absorbent granules react irreversibly with carbon dioxide. Sodasorb (manufactured by W. R. Grace, Lexington, Mass.), a mixture

of hydrated lime, sodium hydroxide, potassium

hydroxide, and inert materials, reacts with carbon

dioxide according to the following equations:

1. CO2 + H2O H2CO3

2. 2H2CO3 + 2NaOH + 2KOH

Na2CO3 + K2CO3 + 4H2O + Heat

3. 2Na2CO3 + 2Ca(OH)2 + K2CO3

2CaCO3 + 2NaOH + 2KOH + Heat

The net reaction can be expressed as follows:

4. Ca(OH)2 + CO2 CaCO3 + H2O + Heat

gen and nitrous oxide in the common gas outlet (see

Figure 7-27). An oxygen sensor tee is connected to

the vaporizer port (see Figure 7-14), and the inspiratory breathing circuit is attached to one limb of the

tee and the oxygen sensor housing is attached to the

other limb.

The FAM Model 885 vaporizer is well designed,

versatile, functional, and safe in the hands of anesthesia providers who are familiar with how it works.

Breathing Circuit

The circuit has a breathing-circuit pressure gauge,

an oxygen monitor, an oxygen flush valve, and a

nonadjustable pressure-relief valve (which releases

gases to the atmosphere if the circuit pressure exceeds 60–80 mm Hg) (see Figures 7-27 and 7-31).

The adult circuit has, in addition, an adjustable

pressure-limiting valve (ie, the pop-off valve), a 3-

L rebreathing bag, two one-way valves, two corrugated breathing tubes, a scavenger, a carbon dioxide absorber, a Y-piece, an elbow, and an adult’s

face mask (see Figure 7-27 and Figure 7-36). The

pediatric partial nonrebreathing circuit is attached

to the vaporizer port and has a tee connector, a

breathing tube, a 1-L rebreathing bag, a one-way

scavenger valve, and a child’s face mask (Figures

7-37 and 7-38). When using the pediatric circuit, it

is essential to close the pop-off valve to prevent the

loss of gases to the atmosphere.

Oxygen Flush Valve

The oxygen flush valve is mounted in front of the

flowmeter manifold, behind the breathing pressure

gauge, and between the flowmeter control knobs

for metabolic oxygen and oxygen-for-vaporizer (Figure 7-39). The valve is identified by a white semicircular label with the words OXYGEN FLUSH printed

in black letters. When the anesthesia provider

presses down on the oxygen flush valve, the spring

pressure holding a ball valve against a valve seat is

counteracted, and oxygen is allowed to flow into

the breathing circuit at a flow rate of approximately

40 L/min (Figure 7-40). Releasing the pressure on

the button allows the spring to reseat the ball valve.

Carbon Dioxide Absorber

A standard two-chamber carbon dioxide absorber

is positioned beneath the control head (see Figure 7-

12 and Figure 7-41). Once the chambers are filled

with carbon dioxide–absorbent granules, the unit is

secured with a clamping knob. If the clamping

Fig. 7-36. The Field Anesthesia Machine (FAM) Model

885A is configured with an adult breathing circuit. A

corrugated hose is attached to the scavenger port of the

pop-off valve. The inspiratory limb of the breathing

circuit is attached to the outlet port near the vaporizer,

and the expiratory limb is attached to the inlet port near

the exhalation valve. Photograph: Printed with permission from Ohmeda, Inc, Madison, Wis.
Military Anesthesia Machines

159

Fig. 7-37. A schematic drawing of the

pediatric nonrebreathing circuit. The

circuit is the same as the adult system

in Fig. 7-14 except that the mixed gases

do not recirculate. Mixed gases enter

the tee connector (19) and flow through

a short tube (20) into the rebreathing

bag (21). Squeezing the rebreathing bag

forces the mixed gases into the patient.

Exhaled gases pass through the rebreathing bag, the scavenger valve (22),

and out the gas-evacuation tubing.

Low-flow rates are associated with

partial rebreathing. The pop-off valve

must be closed when using the pediatric circuit to prevent significant loss of

gases to the atmosphere. Drawing:

Printed with permission from Ohmeda,

Inc, Madison, Wis.

The granules most frequently used in the United

States have been Sodasorb, SODALIME USP/NF

(manufactured in England by Molecular Products,

Ltd.; distributed in the United States by PuritanBennett, Lenexa, Kan.), and Baralyme (manufactured by Allied Healthcare Products, Inc., St. Louis,

Mo.). Table 7-1 compares some of the basic characteristics of the three granules. Figures 7-42 and

7-43 illustrate the differences in the three granules’

absorption of carbon dioxide. Granules are

provided in different kinds of packaging (Figure

7-44).

Carbon dioxide–absorbent granules are imbedded with ethyl violet, an indicator dye, which

changes from white to purple at pH 10.3. AbsorpFig. 7-38. Field Anesthesia Machine (FAM) Model 885A

configured with a pediatric nonrebreathing circuit. Fresh

gases flow from the outlet port near the vaporizer to the tee

of the pediatric nonbreathing circuit. The pop-off valve of

the FAM is closed to prevent gas escaping to the atmosphere. Scavenged gases leave the tip of the rebreathing bag

and flow into a corrugated hose. Photograph: Printed with

permission from Ohmeda, Inc, Madison, Wis.
Anesthesia and Perioperative Care of the Combat Casualty

160

Fig. 7-39. Diagram of the top view of

the Field Anesthesia Machine (FAM)

Model 885A showing the position of

the oxygen flush valve. Note the

fluted oxygen needle valve, the adjustable pressure-limiting (pop-off)

valve, and the two breathing-circuit

check valves. The breathing-pressure

gauge is in the horizontal position,

making it somewhat difficult to read.

Two orifices in the vaporizer control

valve read ON. The nonadjustable

pressure-relief valve can be seen immediately adjacent to and to the left

of the breathing-pressure gauge.

Redrawn with permission from

Ohmeda, Inc, Madison, Wis.

Fig. 7-40. How the oxygen flush valve works in the Field Anesthesia Machine (FAM) Model 885A. (a) A ball-valve

retaining spring is holding the ball valve against the valve seat, preventing oxygen from escaping into the machine

outlet. (b) The flush button has been pushed in, counteracting the pressure from the ball-valve retaining spring. As the

pin moves, the ball valve is lifted off the valve seat, and oxygen at a pressure of 40 psig escapes into the machine outlet

at 40 to 60 L/min. Photograph: Printed with permission granted by Medical Systems Division, Ohmeda, Inc, Madison, Wis.

a b

tion of carbon dioxide is not the same throughout

the canister. Figure 7-45 depicts the zones of absorption; the granules immediately adjacent to

and along the top encounter carbon dioxide first.

Once the granules are purple, their structures are

permanently changed and they should be discarded

(Figure 7-46).

Oxygen Monitor

An oxygen monitor is assembled for use with the

following parts: oxygen monitor, tee, cable, oxygen

sensor cartridge, mounting bracket, and batteries.

The heart of the oxygen monitor is the galvanic cell

sensor cartridge (Figure 7-47). Oxygen molecules
Military Anesthesia Machines

161

TABLE 7-1

COMPARISON OF COMMERCIALLY AVAILABLE CARBON DIOXIDE–ABSORBENT GRANULES

SODALIME USP/NF* Sodasorb† Baralyme‡

Attribute (4–8 mesh w/v granules) (4–8 mesh w/v granules) (4–8 mesh w/v agglomerates)

Moisture (%) 16.3 14.7 14.4

NaOH content (%) 3.01 0.82 0.3

KOH content (%) 0.01 2.1 3.3

Bulk density (g/mL) 0.82 0.83 0.97

Attrition (%) 92.7 95.2 94.1

Crush strength (%) 91.9 94.1 90.5

Hardness (%) 96.2 90.1 89.0

Mesh analysis:

> 8 mm 0 0 0

4.75–8 mm 0.9 1.7 5.9

2.36–4.75 mm 89.1 89.9 87.9

0.42–2.36 mm 9.4 7.3 5.2

< 0.42 mm 0.6 1.1 1.0

*Manufactured by Molecular Products, Ltd (England); distributed in the US by Puritan-Bennett, Lenexa, Kan

†Manufactured by WR Grace, Lexington, Mass

‡Manufactured by Allied Healthcare, St Louis, Mo

Information provided by Puritan-Bennett Corporation, Lenexa, Kan, distributors of SODALIME USP/NF.

Fig. 7-41. Right side of the absorber head of the Field Anesthesia Machine (FAM) Model 885A. A two-canister carbon dioxide absorber is positioned directly below the flowmeter manifold. After the absorption granules have been placed in the

absorber, the absorber’s locking mechanism is gently tightened to avoid leaks between the two chambers and around the

gaskets. Overtightening the locking mechanism will warp the

canister walls, causing permanent leaks. Protective devices

used during storage are shown in place. The vaporizer’s

filling port, temperature gauge, and drain cock are shown.

Fluid accumulating in the absorber can be drained by opening

the drain plug. Redrawn with permission from Ohmeda, Inc,

Madison, Wis.
Anesthesia and Perioperative Care of the Combat Casualty

162

CO2 Breakthrough (% Volume)

Time (Minutes)

Fig. 7-42. Length-of-life comparison of

carbon dioxide–absorbent granules. A

closed-circuit test was done with 5% CO2

at 500 mL • 20 breaths per minute. Carbon dioxide breakthrough occurred first

with Baralyme (manufactured by Allied

Healthcare, St Louis, Mo). Sodasorb

(manufactured by WR Grace, Lexington, Mass) and SODALIME USP/NF

(manufactured by Molecular Products,

Ltd (England); distributed in the United

States by Puritan-Bennett, Lenexa, Kan)

absorbed more carbon dioxide than

Baralyme. Information provided by Puritan-Bennett Corporation, Lenexa, Kan,

distributors of SODALIME USP/NF.

SODALIME Sodasorb Baralyme

USP/NF

Fig. 7-43. Comparison of carbon dioxide loading by three

absorbent granules. A closed-circuit test was done with 5%

CO2 at 500 mL • 20 breaths per minute. Carbon dioxide

load was complete when 0.5% CO2 appeared in the exit gas

from the absorber. Baralyme (manufactured by Allied

Healthcare, St Louis, Mo) absorbed less carbon dioxide

than Sodasorb (manufactured by WR Grace, Lexington,

Mass) or SODALIME USP/NF (manufactured by Molecular Products, Ltd; distributed in the US by Puritan-Bennett,

Lenexa, Kans). Information provided by Puritan-Bennett

Corporation, Lenexa, Kans, distributors of SODALIME

USP/NF.

Fig. 7-44. Carbon dioxide–absorption granules can be

purchased in a variety of packages. Sodasorb is available

in large buckets, small sacks, and prefilled canisters.

Photograph: Printed with permission of WR Grace & Co,

Lexington, Mass.

Fig. 7-45. Zones of absorption in the

carbon dioxide–absorber head. Exhaled

gases enter the top of the carbon dioxide–absorber head. Granules in the A

areas are rapidly depleted and change

from white to purple very early. Granules in the Band C zones change slowly.

Photograph: Reprinted with permission from Conry WA, Seevers MH.

Studies in carbon dioxide absorption.

Anesthesiology. 1943;4:160.

CO2 Load/L/kg
Military Anesthesia Machines

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a b

Fig. 7-46. (a) Normal structure of carbon dioxide–absorption granules before exposure to carbon dioxide (scanning

electron micrograph, original magnification X 3,000). (b) Carbon dioxide–absorbent granules undergo irreversible

structural changes after absorbing carbon dioxide. Soda lime granules become less defined and look cokelike (scanning

electron micrograph, original magnification X 3,000). Reprinted with permission from Sato T, Hori T, Yusa T, Fujii A.

The surface structure of carbon dioxide absorbents observed with scanning electron microscopy. Jap J Anes. 1970;19(1):26.

In Japanese.

selectively pass through a Teflon (polytetrafluoroethylene, manufactured by Du Pont Polymers, Wilmington, Del.) membrane and react with

gold to produce hydroxyl ions (Figure 7-48). Hydroxyl ions then react with lead to release electrons,

which create a voltage output across an external

load resistor. Computer chips allow the electron

flow to be displayed as the percentage of oxygen

(Figure 7-49). High– and low–percentage-of-oxyFig. 7-47. An oxygen sensor housing showing the galvanic cell sensor cartridge. A cable from the housing

connects the cartridge to the processor in the monitor,

and the opposite end is placed in the tee of the inspiratory

limb of the breathing circuit. Photograph: Printed with

permission of Ohmeda, Inc, Madison, Wis.

gen alarms are included. Sensor life is exposuredependent. Each sensor is initially packed in an

inert gas and if stored under refrigeration at 6°C ±

3°C (CAUTION: do not freeze), can be expected to last

a long time. Refrigeration is not always available in

the field, so the replacement sensors should be

stored (when possible) between 18°C and 22°C and

between 50% and 60% relative humidity. Lifespan in

use (approximately 438,000 percent hours) is determined by the time of exposure (in hours) and the

concentration of oxygen (as a percentage). For example, the sensor would last 1 year if exposed to 50%

oxygen but only 6 months if exposed to 100% oxygen.

After the tee is inserted in the breathing circuit

between the vaporizer outlet port and the inspiratory limb of the breathing circuit, the oxygen sensor

is inserted in the remaining open port of the tee. A

cable connects the sensor to the monitor mounted

on the bracket of the absorber head (see Figures

7-13 and 7-14).

Checkout and Maintenance

Each FAM’s Instruction and Service Manual1 outlines in detail how to set up the machine, contains a

checklist to complete prior to use, and describes

how to maintain and repair the machine. In the
Anesthesia and Perioperative Care of the Combat Casualty

164

Fig. 7-48. How an oxygen galvanic cell sensor works. Oxygen molecules selectively pass through a Teflon

(polytetrafluoroethylene, manufactured by Du Pont Polymers, Wilmington, Del) membrane and immediately react

with gold (Au, the cathode), producing hydroxyl ions. The hydroxyl ions pass into the electrolyte bath and react with

lead (Pb, the anode) to form lead oxide and release electrons. These electrons produce a current proportional to the

number of oxygen molecules that are reduced at the gold cathode. An external load resistor connects the anode and

the cathode. Reprinted with permission from Schreiber P. Anesthesia Equipment, Performance, Classification and Safety.

New York, NY: Springer-Verlag; 1972: 130.

back of the manual are blow-up illustrations of the

parts, and numbers for ordering parts. A videotape, Set Up and Use of the Military Field Anesthesia

Machine,

6 is also available to assist the first-time

user in how to give an anesthetic with the FAM.

Once the machine has been set up, it is important

to perform a checkout of the machine prior to the

administration of anesthesia. The FAM will not

require the same checkout as an anesthesia machine

meeting the Standard Specification for Minimum Performance and Safety Requirements for Components and

Systems of Anesthesia Gas Machines7 defined by the

American Society for Testing and Materials (ASTM)

because it was manufactured prior to the standards.

The FAM instruction manual outlines a specific

checkout list covering the following areas1:

• visual inspection,

• high-pressure gas circuit check,

• low-pressure gas circuit check,

• adult breathing circuit check,

• pediatric breathing circuit check,

• the oxygen monitor,

• the gas-ratio output of metabolic oxygen

and nitrous oxide,

• zeroing the breathing-circuit pressure

gauge, and

• the nonadjustable pressure relief valve.

In three different places in the instruction manual,

the manufacturer warns in boldface type:

“CAUTION: No repair should ever be undertaken or

attempted by anyone not having experience repairing devices of this nature.”1(p35)

Internal repairs should not be performed in the field.

Fig. 7-49. An oxygen display of the percentage of oxygen

in the gas mixture. Low-concentration and high-concentration alarms can be used by the anesthesia provider as

conditions warrant. Photograph: Printed with permission of Ohmeda, Inc, Madison, Wis.

O2 O2 O2

Au sensing electrode

Electrolyte bath

Pb counter electrode

Protective disk

Teflon diffusion barrier

Electron flow

Load resistor
Military Anesthesia Machines

165

Simple procedures can be done by anesthesia

personnel or anesthesia technicians. Soda lime

should be changed when the top portion of the

bottom canister begins to turn purple (exhaled

gases pass into the top of the absorber and the top

container is the first to be depleted). Check valves

must be kept clean to avoid sticking. The popoff valve can be dismantled easily and then inspected, washed, dried, and reassembled. Surface

areas need to be wiped regularly with a damp cloth

to keep dirt and grime from collecting. Special

attention must be paid to the absorber and the

rubber goods. Cloudiness on the inside of the

canisters can be removed by buffing with Bon Ami

(feldspar and calcite abrasive cleanser, manufactured by Faultless Starch/Bon Ami Co., Kansas

City, Mo.). Anesthesia agents and oxygen take

their toll on the rubber goods; rubber gaskets and

so forth should routinely be inspected and worn

parts replaced. Preventive maintenance should be

done at least every 4 months when the FAM is in

service.

Sterilization is sometimes difficult to perform in

field conditions, owing to the limited access to

equipment and materials. Most of the components

of the FAM can be washed with a mild alkali detergent and sterilized in a cold germicidal solution.

Steam sterilization and ethylene oxide sterilization

can be used, but with caution.

FAMs in storage with oxygen monitor sensors

should be inspected at least once a year. FAMs without sensors should be inspected every 30 months.

Records should be kept of all inspections, part replacements, and performance of preoperative checks.

Fig. 7-50. The Tri-Service draw-over vaporizer (manufactured by Penlon, Ltd, Abingdon, England) is used by the

British armed forces. Atmospheric air is the primary

carrying gas. The unit can be used with a mechanical

ventilator, supplemental oxygen, and a self-inflating bag.

Photograph: Printed with permission of Penlon Ltd,

Abingdon, England.

Before the discovery of anesthesia, surgery usually lasted less than 5 minutes because patients

could not tolerate the pain. On October 16, 1846,

William Morton performed the first public demonOHMEDA UNIVERSAL PORTABLE ANESTHESIA CIRCUIT

stration of anesthesia by using a draw-over vaporizer to administer ether to Gilbert Abbott.8

 Ether

was poured onto a sponge in a glass container, later

called the Morton inhaler (see Figure 31-5, in Chapter 31, Military Anesthesia From Open-Drop Ether

to Critical Care). A wooden tube was placed in the

patient’s mouth and as the patient inhaled, a valve

was opened, air that was pulled through the glass

container picked up the ether vapor, and the induction of anesthesia began. The Morton inhaler proved

to be cumbersome, inaccurate, and was soon replaced by the simplest form of draw-over vaporizer: a gauze-covered mask (see Figure 7-1).

Ether dripped onto a gauze-covered mask was

widely used in the U.S. military from 1846 to the

end of World War II. After World War II, anesthesia

providers adopted circle systems in civilian hospitals and the use of draw-over vaporizers ended. In the

Vietnam War, a few U.S. military anesthesia providers used draw-over vaporizers, loaned by the Australian Armed Forces, as a novelty. During the Falklands

War, the British armed forces used the Tri-Service

draw-over vaporizer (manufactured by Penlon, Ltd.,

Abingdon, England) with great success (Figure 7-50).

This war was especially suited for a draw-over

vaporizer: it was short, featured highly mobile

forces, and long-standing field hospitals were not

required. British anesthetists continued to praise

the draw-over vaporizer via such vehicles as journal publications and medical meetings. Members

of the U.S. military anesthesia community eventually became interested in the draw-over vaporizer.

Basic research was done on the machine in the

United States, and some military anesthesia provid-
Anesthesia and Perioperative Care of the Combat Casualty

166

Fig. 7-51. The Ohmeda Universal Portable Anesthesia

Circuit (PAC) is shown assembled and ready for use.

Photograph: Printed with permission of Ohmeda, Inc,

Madison, Wis.

ers took draw-over vaporizers with them on volunteer humanitarian missions to the Third World.

Once Operation Desert Shield was mobilized,

military anesthesia providers requested draw-over

vaporizers as backup to the FAMs. The Ohmeda

Universal PAC was chosen as the draw-over vaporizer for the U.S. military (Figure 7-51). Appropriate

paperwork and PAC units were sent to the U.S.

Food and Drug Administration (FDA) for its 510(k)

approval for sale. The FDA was attuned to the

needs of the military and was able to give its approval before the onset of Operation Desert Storm.

This approval allowed the PAC to be sold to the

military but restricted its use to wartime conditions. The manufacturer was requested to include

the following statement in the PAC Operation and

Maintenance Manual:

WARNING: The Ohmeda Universal PAC system is

intended for use only in military battlefield situations where conventional closed, semi-closed continuous low flow or other more sophisticated anesthesia systems are not available. Failure to utilize a

conventional anesthesia system when available significantly increases the risk of patient injury.9(p3)

PAC units were taken to Saudi Arabia and became an inventory item in the DEPMEDS system.

The majority of anesthesia providers in the United

States have not seen a draw-over vaporizer, are

only vaguely familiar with its operating principles,

and do not know how to use one safely. Learning to

use a draw-over vaporizer is not complicated, but it

was extremely difficult to train our military personnel during the Persian Gulf War. Anesthesia standards of care, anesthesia machine standards,7 and

medicolegal pressures would not allow the routine

use of draw-over vaporizers in civilian hospitals

and stateside military hospitals. Efforts have recently been begun to establish training sites at stateside military hospitals to provide instruction.

Specifications and Operation

The PAC fits into a small container about the size

of a small briefcase (see Figure 7-3). Figure 7-52 is

a labeled diagram of the components and Figure 7-

53 shows the PAC assembled. The PAC unit weighs

about 5 lb and measures 71⁄2 in. x 51⁄8 in. x 33⁄4 in; the

vaporizer holds 85 mL of liquid anesthetic and has

Fig. 7-52. Break-out view of the Ohmeda Universal Portable

Anesthesia Circuit (PAC). Atmospheric air is pulled through

the air inlet and the vaporizer by the recoil inflation of the

self-inflating bag. The reservoir hose is a catchment area for

supplemental oxygen to accumulate during the respiratory

cycle. A nonrebreathing valve at the face mask keeps the

air/anesthetic mixture flowing in one direction. As the selfinflating bag is squeezed, the patient’s lungs are ventilated.

Elastic recoil of the patient’s lungs empties the exhaled

gases into the room via a scavenger hose. During inflation

of the self-inflating bag, air is drawn through the vaporizer,

picking up anesthetic vapor and filling the self-inflating bag

and connecting tube with air/anesthetic mixture. Photograph: Printed with permission of Ohmeda, Inc, Steeton,

West Yorkshire, England.
Military Anesthesia Machines

167

Fig. 7-53. Schematic of the Portable Anesthesia Circuit (PAC). Air is drawn through the air inlet into the vaporizer. A

portion of the air enters the vaporizer chamber to pick up the anesthetic vapor and combine with the portion of air that

bypassed the vaporizing chamber. Note the nonreturn valve at the vaporizer outlet and the nonrebreathing valve at

the face mask. Both function to ensure one-way airflow. A supplementary oxygen inlet is present between the air inlet

and the vaporizer inlet. Oxygen can accumulate in the reservoir hose to provide enrichment of the carrier gas.

Photograph: Printed with permission of Ohmeda, Inc, Steeton, West Yorkshire, England.

a nominal working temperature range of 18°C to

35°C (65°F–95°F).9

A one-way valve at the face mask, combined with

the nonreturn valve at the vaporizer outlet, ensures

the one-way movement of air from the air inlet to

the face mask (Figure 7-53). Air is drawn through

the PAC by the recoil negative pressure created

by filling of the deflated self-inflating bag. Air

flow within the vaporizer is governed by a rotary

valve, which is controlled by adjusting the concentration setting dial (Figure 7-54). Two calibrated

concentration dial disks are available: isoflurane/

halothane and diethyl ether/enflurane (Figure 7-

55). The reversible dial disk, graduated from

0.5% to 5%, is provided as a convenient concentration dial for isoflurane/halothane. The main dial,

which is attached to the vaporizer, is graduated

alphabetically from A to F, and a label permanently affixed to the vaporizer gives the output for

diethyl ether, enflurane, halothane, and isoflurane

at each setting. As air enters the vaporizer, the

vertical rotary valve divides the stream; some enFig. 7-54. Cross section of the Portable

Anesthesia Circuit (PAC) Universal

vaporizer. A rotary valve is connected

to the concentration dial. Changing

the concentration dial setting changes

both the amount of air bypassing the

vaporizing chamber and the amount

entering the vaporizing chamber. The

vaporizer chamber holds 85 mL of

anesthetic liquid; 13 mL is retained in

the wick. A bimetallic strip (see Fig. 7-

58) serves as a temperature-compensation valve. Photograph: Printed with

permission of Ohmeda, Inc, Steeton,

West Yorkshire, England.

Inlet

Rotary Valve

Temperature

Compensating Valve

Outlet

Wick

Dial

Bypass

Vaporizing

Chamber
Anesthesia and Perioperative Care of the Combat Casualty

168

a b

Fig. 7-55. The diagram (a) shows the agent-concentration dials of the Portable Anesthesia Circuit (PAC). The reversible

dial disk has halothane on one side and isoflurane on the other. Gradations of concentration from 0.5% to 5% are

present for both agents. The main agent-concentration dial is divided alphabetically from A to F. The tabular

information (b) is affixed to the vaporizer for interpreting the concentration output for each agent. The concentration

output of the main dial is graduated from A to F for diethyl ether, enflurane, halothane, and isoflurane. Filling the

vaporizer with isoflurane and setting the main concententration dial at C will deliver 2.15% isoflurane at a flow rate

of 4 to 6 L/min and a temperature of 20°C to 22°C. Photographs: Printed with permission of Ohmeda, Inc, Madison, Wis.

ters the vaporizer chamber and some bypasses the

vaporizer. In the Tri-Service draw-over vaporizer,

a sliding valve opens and closes the vapor chamber

(Figure 7-56).10

As the PAC bypass gap is reduced, greater proportions of air enter the vaporizing chamber. A

wick in the vaporizing chamber increases the surface area for evaporation. Heat is required for

evaporation of the liquid anesthetic. A temperature

compensation valve controls the orifice where the

mixture of air and anesthetic exits the vaporizing

chamber to mix with the air bypassing the vaporizing chamber.

Output from the vaporizer is dependent on flow

rate (tidal volume and respiratory rate), inspiratory/expiratory rate, and temperature.11 High flow

rates do not allow enough time for temperature

compensation, so the liquid cools rapidly and outFig. 7-56. Cross section of the Tri-Service draw-over vaporizer, which is used by the British armed forces. Air enters

the vaporizer and a portion of the stream goes into the

vaporizing chamber (C) through the inlet of the vapor

chamber opening controlled by a sliding valve (R). The

remainder of the air stream enters the bypass passage (B).

Wicks (W) of stainless steel mesh increase the evaporation

surface area inside the vaporizing chamber. A heat reservoir (H) filled with antifreeze liquid compensates for temperature changes. Air and anesthetic vapor pass out the

vaporizing chamber outlet (E) to mix with the air coming

through the bypass passage. Two different paths (1 and 2)

through the vaporizing chamber provide a method of temperature and flow compensation. Photograph: Printed with

permission of Penlon, Ltd, Abingdon, England.

Reversible dial

discisoflurane/

halothane

Dial -

diethylether/

enflurane

Dial stop and

location pin

Drain cap

Dial screw
Military Anesthesia Machines

169

Airflow Rate (L/min)

Percentage (v/v) Halothane or Isoflurane

Fig. 7-57. The effect of flow rate on output concentration for halothane and

isoflurane from the Portable Anesthesia

Circuit (PAC). Lower concentrations are

seen at higher levels of flow. The most

accurate outputs are between 3 and 6 L/

min. Photograph: Printed with permission of Ohmeda, Inc, Steeton, West Yorkshire, England.

put falls (Figure 7-57). Temperature compensation

in the PAC is accomplished by a bimetallic

strip that controls the vaporizing chamber outlet

orifice (Figure 7-58). Flow rates between 4 and 6 L/

min for halothane, isoflurane, and enflurane deliver concentrations close to the dial settings. If the

flow rate is kept constant and the temperature of the

liquid anesthetic is raised or lowered during ambient temperature changes, the output of the agent

will become temperature dependent (Figure 7-59).

At about 22°C, the output concentration is approximately equal to the dial setting. Vapor pressure is

determined by temperature; thus, the amount of evaporated anesthetic is reduced at low temperatures and

increased at high temperatures. The manufacturer

warns that “potentially hazardous excessive concentrations of anesthetic agent may occur at temperatures

above 35°C (95°F).”9(p11) Tipping the vaporizer can

result in unpredictable output concentrations.

An estimated hourly drug usage can be calculated by using the following formula12:

3 • % • flow (L/min) = agent usage (mL/h)

For example, if the vaporizer is set to deliver 1%

halothane at 5 L/min, then

3 • 1% • 5 L/min = 15 mL/h

of halothane will be used.

Fig. 7-58. In this bimetallic strip, brass has been welded to

nickel. The strip’s bending depends on the temperature

and the difference in the linear expansion coefficient of

brass and nickel. Temperature compensation for the Portable Anesthesia Circuit (PAC, manufactured by Ohmeda,

Inc, Steeton, West Yorkshire, England) is controlled by a

similar bimetallic strip at the vaporizing chamber exit (see

Fig. 7-54).
Anesthesia and Perioperative Care of the Combat Casualty

170

Temperature (°C)

Percentage v/v Halothane or Isoflurane

Fig. 7-59. Effect of temperature on the output concentration of halothane and isoflurane from the Portable Anesthesia Circuit (PAC). The most stable output is found

between 21°C and 27°C. Photograph:

Printed with permission of Ohmeda, Inc,

Steeton, West Yorkshire, England.

A nipple is provided at the vaporizer inlet for

connecting supplementary oxygen. Oxygen improves the safety margin for the patient and should

be added whenever available. Availability of oxygen concentrators in combat areas will greatly enhance the safety of draw-over vaporizers. A ventilator and scavenger apparatus can be used with the

PAC.9 A training film is also available on how to use

the PAC.13

Checkout and Maintenance

A visual inspection must be made of the vaporizer, hoses, self-inflating bag, nonrebreathing valve,

and any other attachments. Make sure the concentration dial on the vaporizer is the one for the liquid

anesthetic agent in the vaporizer. Internal leaks can

be tested by squeezing the self-inflating bag with

the vaporizer in the ON position, capping the air

inlet and oxygen nipple, and releasing the selfinflating bag. The bag should not reinflate. External leaks can be detected by capping the face mask

and expiratory valve ports and by squeezing the

self-inflating bag. The bag should not deflate.

Clean the exterior with a damp cloth. Be sure to

completely drain the vaporizer of anesthetic agent

and dry the wicks before filling with a different

agent. Dry the wicks by passing air through the

vaporizer (minimum rate of 750 mL at 24 cycles per

minute), until no vapor can be smelled at the vaporizer outlet. This drying process may take 15 to 20

minutes for isoflurane or halothane. Make sure that

the vaporizer wicks are dried thoroughly when

storing the vaporizer.

The manufacturer recommends yearly service if

the vaporizer is used daily, servicing every 2 to 3

years with intermittent use, and every 5 years with

occasional use if the vaporizer is stored dry.

IDEAS FOR FUTURE MILITARY ANESTHESIA MACHINES

Comparison of the FAM Model 885A and the

PAC with conventional anesthesia machines in stateside civilian and military hospitals finds them sorely

deficient in safety features. Patient monitoring in

combat areas can easily be brought up to standard

with excellent portable monitors now available as

off-the-shelf items (Figure 7-60). Elevating the FAM

and PAC to the level expected of anesthesia machines in the United States is not possible in combat.

The central problem, in the opinion of this writer, is:

How do we train anesthesia providers to use the

two available anesthesia machines when these machines do not meet current standards? For training

purposes, many military hospitals are putting the

FAM Model 885A in the operating room with a

standard anesthesia machine and transferring the

machine’s monitors to the FAM. Some military

hospitals are even transferring the standard machine monitors to a PAC, denying that the PAC is an

anesthesia machine (calling it an “apparatus”), using the PAC without the consent of the patient, and

ignoring the warning in the instruction manual.14

Training for the FAM and the PAC is difficult to

provide in military hospitals, since they are expected to meet the same patient-care standards as

civilian hospitals. Anesthesia providers in civilian

hospitals would be aghast to see a FAM 885A or a PAC

in one of their operating rooms. Neither machine
Military Anesthesia Machines

171

Fig. 7-60. PROPAC portable patient monitor. A unit this

size can be fitted to monitor temperature, the electrical

activity of the heart, pulse oximetry, blood pressure

(direct and indirect methods), end-tidal carbon dioxide,

venous pressure, and pressure from a pulmonary catheter. Photograph: Printed with permission of Protocol

Systems, Inc., Beaverton, Ore.

meets the ASTM standards for anesthesia machines

and the medicolegal implications of using either machine “as is” would be unthinkable. The FAM 885A,

with state-of-the-art machine monitoring transferred

from an anesthesia machine that meets all ASTM

standards, can be used safely in the operating room if

rigid protocols are established and if approval is

given by the patient. Such programs are being or

have been established at Naval Hospital, San Diego,

California; Brooke Army Medical Center, San Antonio, Texas; and Walter Reed Army Medical Center,

Washington, D. C. Exposure to FAM 885A training

for anesthesia personnel in the reserves is still rather

limited, but formalizing the present programs and

instituting some manner of required certification

may widen the scope of available training sites.

Adaptation of the PAC to present ASTM standards is not possible because the standards do not

address such outdated technology. There are those

within the military who have used the PAC in

training programs in military hospitals in the United

States in recent years by stating that the PAC is not

an anesthesia machine and then using such logic to

remove the medicolegal implications from the use

of the machine. However, in the view of this author,

the PAC is a draw-over vaporizer anesthesia machine,

and, as such, must meet the same standards of

patient care as those used in any hospital in the

United States. A carefully prepared teaching program could allow the PAC to be used in military

hospitals. The first step would be for participants to

become familiar with the PAC by reading the instruction manual, watching the videotape, listening

to a didactic program, and then administering an

anesthetic to animals. The second step would be to

obtain permission from the risk-management department of the hospital to use the PAC in the

operating room. Transferring the monitors from an

ASTM-qualified anesthesia machine to the PAC

and using state-of-the-art patient monitors would

be essential. The third and final step would be to

obtain permission from the patient. A carefully

designed plan would allow the PAC to be used

safely in the operating room and would allow us to

train military personnel in a formalized program

with some kind of certification or record of training.

Some military centers are designing programs to

allow restricted use of the PAC in the operating

room. To push forward and use the PAC without a

formalized protocol (including patient permission)

is to flout the manufacturer’s warning, which explicitly states that such use will significantly increase the risk to the patient. Plans are under way

at the U.S. Army Medical Materiel Development

Activity, Fort Detrick, Frederick, Maryland, to (a)

upgrade a few of the FAM Model 885As with machine monitors and single-agent vaporizers to more

closely approximate ASTM standards,7 and (b) design a new FAM that will be more versatile, weigh

less, and meet all the ASTM standards. A Joint Services Working Group has reviewed the characteristics

of both the upgrade and a new machine. Anesthesia

machine manufacturers have submitted designs for

the upgrade. Money has been allocated for a military–

industry cooperative effort to develop a new FAM.

The PAC might be improved by adopting some

of the features of the ULCO Field Anaesthesia Apparatus (manufactured by ULCO Engineering Pty.

Ltd., Marrickville, NSW, Australia) that has been

developed for the Australian Armed Forces (Figure

7-61).15 Its total weight is 55 lb. Versatility is the

keynote feature of the apparatus. Different breathing circuits and multiple gas sources (eg, compressed-gas cylinders, pipeline gases, oxygen concentrators) can be used. Two Oxford Miniature

Vaporizers (OMV, manufactured by Penlon, Ltd.,

Abingdon, England) connected to Tri-Service drawover vaporizers are the heart of the apparatus (Figure 7-62) The machine can be used as a circle system

or as a nonrebreathing system. In the circle-system

mode, a carbon dioxide absorber, and either compressed-cylinder or pipeline oxygen and/or nitrous

oxide are required. When the self-inflating bag is

used, the oxygen in atmospheric air is sufficient or

supplemented oxygen can be added.
Anesthesia and Perioperative Care of the Combat Casualty

172

Fig. 7-61. The ULCO Anaesthesia Apparatus is used by the Australian Armed Forces. Two agent-specific Oxford Miniature Vaporizer (OMV) Tri-Service draw-over vaporizers (manufactured by

Penlon, Ltd, Abingdon, England) are connected in series.

Flowmeters are used for compressed or piped oxygen and nitrous

oxide when available. A self-inflating bag converts the apparatus

to a nonrebreathing circuit and can be used with atmospheric air

and supplemental oxygen. A small carrying case houses the 55-lb

unit. A mechanical ventilator and a carbon dioxide absorber can be

used with the apparatus. Photograph: Printed with permission of

ULCO Engineering Pty, Ltd, Marrickville, NSW 2204, Australia.

Fig. 7-62 In the basic configuration of the ULCO Field Anaesthesia Apparatus (a), flowmeters for oxygen and nitrous

oxide are used with compressed or pipeline gases when available. Two single-agent (halothane and trilene) Oxford

Miniature Vaporizer (OMV) Tri-Service draw-over vaporizers (manufactured by Penlon, Ltd, Abingdon, England) are

connected in series (see Figure 7-61). Atmospheric air enters the circuit when the unit is used with the self-inflating

bag. A one-way valve prevents reverse flow in the circuit. An oxygen flush valve is activated when oxygen under

pressure is attached. The common gas outlet is where the various circuit configurations are connected. When

configured as a closed-circuit system (b), the circuit’s fresh-gas connector is attached to the common gas outlet of the

anesthesia apparatus. A carbon dioxide absorber with one-way valves, exhaust valve, patient breathing hoses, and

connections for a ventilator or rebreathing bag are present. When configured as a non- (continued on p 173)

a
Military Anesthesia Machines

173

rebreathing circuit (c), a tee piece is attached to the common gas outlet of the anesthesia apparatus. A self-inflating bag

is connected to one arm of the tee, and the patient breathing hose is attached to the other arm of the tee. A

nonrebreathing valve at the connection of the face mask allows fresh gas to enter the patient’s lungs and exhaled gases to

exit into the room. Photographs: Printed with permission of ULCO Engineering Pty, Ltd, Marrickville, NSW 2204, Australia.

b

c
Anesthesia and Perioperative Care of the Combat Casualty

174

supplemented oxygen can be added.

SUMMARY

Military anesthesia machines have been essential

for the care of the wounded since the discovery of

anesthesia in 1846. Each war and humanitarian

effort has required military anesthesia providers to

adapt to the equipment provided. At present, the

military has in inventory the FAM Model 885A and

the PAC anesthesia machines. Both machines are

adequate for their designed task. The PAC has a

limited application for rapid deployment and a

short battle. Anesthesia providers and standards

have outpaced the FAM Model 885A. Expectations

of anesthesia providers and standards can only be

met by a stop-gap measure of a FAM upgrade and

an eventual replacement with a new FAM.

REFERENCES

1. Ohmeda. Instruction and Service Manual With Illustrated Parts List. Model 885A. Anesthesia Apparatus, Gas, Nitrous

Oxide, Oxygen and Volatile Liquid Anesthetics, Portable 4-Cylinder Capacity. Stock Number 0178-1683-000. Madison, Wis: Ohmeda; Sept 1990. National Stock Number 6515-01-185-8446, Defense Personnel Support Center.

2. Compressed Gas Association. Characteristics and Safe Handling of Medical Gases. Manual P-2. 7th ed. Arlington,

Va: Compressed Gas Association, Inc; 1989.

3. Parbrook GD, Davis PD, Parbrook EO. Basic Physics and Measurements in Anaesthesia. 2nd ed. Norwalk, Conn:

Appleton-Century-Crofts; 1986.

4. Food and Drug Administration. Medical Device Report 372985. Product: 10-134 Anesthesia Units. Common

Device Name: Military Anesthesia Machine. Washington, DC: FDA; 25 March 1993.

5. DesMarteau JK. Flow through the copper kettle flowmeter. Anesthesiology. 1984;61:789.

6. Department of Anesthesiology, Uniformed Services University of the Health Sciences. Set Up and Use of the

Military Field Anesthesia Machine. March 1991. Videotape; Beta, VHS, Umatic formats. Production Identification

Number 503005. Bethesda, Md: Dept of Anesthesiology, USUHS; Military Medicine Education Institute.

Requests, US Army, Navy, Marine Corps: Chief, Joint Visual Information Activity, ATTN; ASQNV-OJVT-ID,

Tobyhanna Army Depot, Pennsylvania 18466-5100; Air Force: Commander, 1352 AVS/DOL, Bldg. 248, Norton

Air Force Base, California 92409-5996.

7. American Society for Testing and Materials. Standard Specification for Minimum Performance and Safety Requirements for Components and Systems of Anesthesia Gas Machines. Philadelphia, Pa: ASTM; March 1989. F 1161-88.

8. William TG Morton (1819–1868), demonstrator of ether anesthesia. JAMA. 1965;194:190. Editorial.

9. Ohmeda. Operation and Maintenance Manual: Ohmeda Universal PAC. West Yorkshire, England: Ohmeda. Dec

1990. Part No. 1101-0001-000.

10. Penlon, Ltd. User’s Instruction Manual: OMV Fifty Vaporizer. Abingdon, England: Penlon, Ltd; Oct 1989. Catalog

No 51216.

11. Kingsley CP, Petty C, Olson K. Anesthesia equipment for austere conditions. In: Grande CM, ed. Textbook of

Trauma Anesthesia and Critical Care. St. Louis, Mo: Mosby–Year Book; 1993: Chap 97.

12. Ohmeda. PAC Range. West Yorkshire, England: Ohmeda; 1985.

13. Draw-over Anesthesia. Videotape. Production No. A1908-94-002. Washington, DC: Department of Motion Picture

Production, Division of Medical Audio-Visual Services, Walter Reed Army Institute of Research; 1994.

14. Casinelli PE, Reynolds PC. Adapting the Ohmeda UPAC draw-over vaporizer for use in the modern operating

room. Milit Med. 1994;159:600–602.

15. ULCO Engineering Pty, Ltd. Manual for ULCO Portable Anaesthesia Apparatus. Marrickville, NSW, 2204, Australia: ULCO Engineering Pty Ltd; ca 1993.
Closed-Circuit Anesthesia

175

RICHARD K. BAUMGARTEN, M.D.*

Chapter 8

CLOSED-CIRCUIT ANESTHESIA

INTRODUCTION

OXYGEN AND POSITIVE-PRESSURE VENTILATION

Inward and Outward Leaks

Conserving Oxygen

POTENT VOLATILE ANESTHETIC AGENTS

Pharmacokinetics

Concentration and Dosage

The Pharmacological Uncertainty Principle

Equipment for Administering Volatile Agents

Square-Root-of-Time Kinetics for Intravenous Agents

SUMMARY

*

Lieutenant Colonel, Medical Corps, U.S. Army (ret); formerly, Associate Clinical Professor of Anesthesiology, Uniformed Services University

of the Health Sciences, Bethesda, Maryland 20814-4799; currently, Senior Staff Physician, Department of Anesthesia and Pain Management,

Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202
Anesthesia and Perioperative Care of the Combat Casualty

176

INTRODUCTION

The military anesthesia provider may be required

to provide many hours of care in battlefield medical

treatment facilities while working under restrictions that make the usual peacetime practice of

anesthesiology infeasible:

• Supplies of compressed gas may be very

limited in the field.

• Most ventilators in the inventory are oxygen powered.

• Nitrous oxide, the most commonly used

anesthetic during peacetime and in civilian

hospitals, has been removed from the U.S.

military field inventory.

With oxygen at a premium, the anesthesia provider

may need to “squeeze the bag,” (ie, to provide

manual positive-pressure ventilation) sometimes for

many hours, when controlled ventilation is required.

Two anesthetic options may aid the anesthesia

provider in these circumstances: (1) regional anesthesia and (2) spontaneous ventilation under general anesthesia. Where appropriate to the injury,

regional anesthetic techniques, such as brachial

plexus blockade and spinal anesthesia, which use a

minimum of supplies, can be used. With certain

caveats, draw-over vaporizers can provide anesthesia with no compressed gas at all.1

 Because ether

is a respiratory stimulant, its use with spontaneous

ventilation in a draw-over system does not require

oxygen supplementation. Potent volatile agents,

such as halothane and isoflurane, are respiratory

depressants; therefore, supplementation with at

least 1 L/min of oxygen is required during spontaneous ventilation. If these agents are utilized with

only air, ventilation should be controlled. The anesthetist must squeeze the bag constantly, because on

room air the patient has little reserve during even

short periods of apnea. Providing manual ventilation for many hours with a draw-over system’s selfinflating reservoir bag can be very uncomfortable.2

Intravenous anesthetics, such as ketamine, opioids,

benzodiazepines, and muscle relaxants can be utilized; however, their use often mandates controlled

ventilation.

Two field anesthesia machines are available for

deployment with the U.S. Army Medical Department: the Field Anesthesia Machine (FAM) Model

885A and the Ohmeda Universal Portable Anesthesia Circuit (PAC, both manufactured by Ohmeda,

Inc., Madison, Wis.) draw-over system (see Chapter

2, Combat Anesthesia Overview and Chapter 7,

Military Anesthesia Machines). The FAM 885A is a

circle system; the PAC is a nonrebreathing system.

A circle system is a closed circuit of gases from

which the patient is breathing. These gases consist

of oxygen, water vapor, carbon dioxide, sometimes

nitrogen, and anesthetic agents, and are confined

within breathing tubes with one-way valves, a reservoir bag, a fresh-gas inlet, a pop-off device (ie, an

adjustable positive-pressure relief valve), and a carbon dioxide absorption canister, which permits

rebreathing of some or all of the exhaled gases. In

a closed circuit, the inflow of gases is set to replace

only those gases taken up by the patient, in order to

maintain the set percentages and volume within the

system. A nonrebreathing system, on the other

hand, contains only an inspiratory limb of tubing, a

reservoir bag, a fresh-gas inflow, and a single nonrebreathing valve between the patient and the system. A nonrebreathing system must supply all of

the tidal volume delivered to the patient as fresh

gas inflow with each breath. This inflow must

contain the appropriate mixture of gases required

for anesthesia, as there will be no equilibration

between patient and system. The closed-circle system efficiently conserves patient heat, water vapor,

anesthetic agent, and oxygen; the nonrebreathing

system is smaller and simpler but conserves nothing, as the patient’s entire tidal volume is lost to the

room or scavenging device.

In its usual semiclosed configuration, the FAM

885A is profligate in its use of compressed gas.

However, when low flows are utilized, it can provide a high fraction of inspired oxygen (FIO2) with

very modest expenditure (0.3–0.5 L/min) of compressed oxygen. The compliant reservoir bag is

comfortable and controlled ventilation can be provided for many hours without undue fatigue. Additionally, the high FIO2 provides a reserve so that

the patient can tolerate short periods of apnea while

the anesthetist performs other tasks (eg, hanging a

unit of blood for transfusion).

During deployment, with compressed gas at a

premium, controlled ventilation will be provided

manually. The closed-circuit technique can be used

advantageously in two ways: (1) to provide controlled ventilation with a high FIO2 for intravenous

techniques and (2) to deliver potent volatile agents

by liquid injection for techniques utilizing sponta-
Closed-Circuit Anesthesia

177

The circle system can be used to provide a high

FIO2 and positive-pressure ventilation while conserving oxygen supplies. This is a very effective

adjunct to total intravenous anesthesia techniques,

especially when a muscle relaxant is used.

To understand low-flow anesthesia with oxygen,

we must consider the various contributions to the

volume of gas in the anesthesia system. The anesthesia system consists of the tubing, reservoir bag,

gas in the carbon dioxide absorber, and the patient’s

functional residual capacity (FRC) (Figure 8-1). For

an adult, the volume of gas in this system is approximately 10 L.4 Several potential positive and

negative contributions to this system occur during

the anesthetic-delivery period. The patient consumes oxygen from the anesthesia system. Normal

adult oxygen consumption (VO2) is approximately

200 mL/min.5 Carbon dioxide produced by the

patient is removed by the carbon dioxide absorber.

During closed-circuit anesthesia, the anesthesia

provider closes the relief valve and adjusts the

oxygen flow to maintain a constant volume in the

anesthesia system. Changes in system volume are

neous or controlled ventilation. Anesthesia personnel deployed with the U.S. Marines during the Persian Gulf War used closed circuit anesthesia with

liquid injection of halothane. With high ambient

temperatures and limited logistical reserves, the

method proved both workable and useful.3

OXYGEN AND POSITIVE-PRESSURE VENTILATION

assessed at end-expiration. When a rising-bellows

ventilator is used, system volume is constant when

the bellows returns to the same height with each

breath. The same principle applies when a reservoir bag is used; however, the extent to which the

bag is filled is assessed relative to the anesthesia

provider’s hand. If the anesthesia system is leakfree, only enough fresh oxygen to replace the

patient’s consumption is required.

Inward and Outward Leaks

In practice, some leaks usually occur, especially

around the face mask or endotracheal tube. Leaks

can be either into or out of the circuit (Figure 8-2). A

leak into the system can occur when negative pressure develops in the circuit, the most common source

being a hanging bellows ventilator. Negative pressure and a potential inward leak can also arise

during spontaneous ventilation. An inward leak

introduces room air (nitrogen and oxygen) into the

circuit. Outward leaks arise when the circuit pressure is positive. During controlled ventilation (eiFig. 8-1. The closed anesthesia system consists of

the circuit, reservoir bag, and the patient’s functional

residual capacity. The total volume of the anesthesia

system for an adult is approximately 10 L. If the circuit

is free of leaks and the system volume is held constant, oxygen flow will equal oxygen consumption.

FRC: functional residual capacity; O2: oxygen; VO2: normal adult consumption of oxygen; a: carbon dioxide

absorbant.

Fig. 8-2. Leaks usually occur in a closed-circuit anesthesia system, including those that incorporate a hanging

bellows ventilator. When the system volume is held

constant, oxygen flow equals oxygen consumption plus

the leak. This is an algebraic sum. An inward leak lowers

the oxygen flow required to maintain system volume,

while an outward leak increases the required flow. FRC:

functional residual capacity; O2: oxygen; VO2: normal

adult consumption of oxygen; a: carbon dioxide absorbant.

Outward

leak

Inward

leak

a a

VO2

VO2

O2 Flow O2 Flow = VO2 + Leak
Anesthesia and Perioperative Care of the Combat Casualty

178

Tc = ——————— = 200 min ther manually controlled or using a rising-bellows

ventilator), circuit pressure will be positive and any

leak will be out of the anesthesia system. A substantial outward leak can also arise when a gas analyzer

or mass spectrometer is used (unless the sampled

gas is returned to the circuit). In common peacetime practice, gas analysis produces the most substantial leak.

The distinction between inward and outward

leaks is important. An inward leak introduces nitrogen into the circuit, which will tend to lower the

FIO2 in the system. When the circuit is closed soon

after induction, the initial FIO2 is usually 0.5 to 0.6.

To understand the effect of an inward leak, consider

a patient with a VO2 of 200 mL/min, an initial

system FIO2 of 0.5 and an inward leak of 10 mL/min.

With an inward leak of 10 mL/min, a fresh-gas

oxygen flow of 190 mL/min will maintain the system volume. During each minute, the inward leak

introduces 8 mL of nitrogen and 2 mL of oxygen.

Each minute, the patient consumes 200 mL of oxygen while 192 mL of oxygen is added to the system.

Therefore, the FIO2 will decrease with time. After 1

hour, 480 mL (60 min • 8 mL/min) of nitrogen will

be introduced into the system. The circuit initially

contained 5,000 mL of nitrogen and 5,000 mL of

oxygen, so after an hour it will contain 4,520 mL of

oxygen and 5,480 mL nitrogen (FIO2 = 0.452). The

FIO2 has decreased by 0.048.

In contrast, outward leaks increase the FIO2 in the

system because the leak removes oxygen and nitrogen, which are replaced with oxygen only. Let us

again consider a patient whose VO2 is 200 mL/min,

and a system with an outward leak of 50 mL/min.

To maintain circuit volume, 250 mL of oxygen per

minute must be added via the fresh-gas flow. During the first minute, the FIO2 is 0.5; therefore, the

leak removes approximately 25 mL of nitrogen,

which is replaced with oxygen. After a minute, the

circuit will contain 5,025 mL of oxygen and 4,975

mL of nitrogen. The FIO2 will have increased slightly.

During the second minute, the leak removes approximately 25 mL [(4,975 ÷ 10,000) • 50 mL = 24.95

mL] of nitrogen. As the system FIO2 increases, less

nitrogen is removed in the leak. This change in FIO2

is actually a continuous process that can be summarized by an exponential expression of the form:

1 – e–t

⁄

Tc

where t represents time and Tc represents the time

constant, which equals the volume divided by the

flow.6 In this example,

10,000 mL

50 mL/min

The initial FIO2 was 50% and the FIO2 of the fresh-gas

flow entering the circuit is 100%; after one time

constant (ie, 200 min), the FIO2 will be 0.835 (ie, 67%

of the difference between 50% and 100%); after two

time constants (400 min), it will be 0.935 (87% of the

difference between 50% and 100%); and after three

time constants, it will be 0.975 (95% of the difference

between 50% and 100%). Note that with leaks of 50

to 100 mL/min, the FIO2 increase is quite slow.

Therefore, when FIO2 is measured during closedcircuit anesthesia, it is quite common to see values

of 0.5 to 0.7 despite the fact that the fresh gas is 100%

oxygen.

There are two additional sources of nitrogen in

the closed anesthesia system. First, nitrogen can

enter the closed system from the release of dissolved nitrogen by body tissues. The total nitrogen

dissolved in the body is approximately 1 L. Because

the volume of the closed system is 10 L, dissolved

nitrogen could potentially lower the FIO2 by one

tenth (1 L÷10 L). Second, nitrogen remains in the

FRC when the circuit is closed. This nitrogen distributes throughout the entire system. As an example, consider an adult patient who is intubated

awake with no preoxygenation. The anesthesia

circuit contains pure oxygen and the circuit is closed

immediately after intubation. The adult patient’s

FRC is approximately 2 L. Because the patient was

breathing room air prior to awake intubation, the

FIO2 in the FRC is 21%. Therefore, the FRC contains

1,580 mL of nitrogen (2,000 mL • 0.79). This nitrogen will be distributed throughout the anesthesia

system, producing an initial FIO2 of 0.84 [(10,000 –

1580) ÷ 10,000 = 0.84]. In this example, the circuit

contained oxygen and the patient’s FRC was the

source of the nitrogen. If the patient is preoxygenated for several minutes with a tight-fitting face

mask, a semiclosed circuit, and high flows of oxygen (4–5 L/min), then the FRC nitrogen can largely

be removed, and when the circuit is closed the

initial FIO2 will be high (0.7–1.0). If, however, a

loose-fitting face mask is utilized, nitrogen will

enter around the mask and be distributed throughout the system. The initial FIO2 may then be as low

as 0.30 to 0.40.

Conserving Oxygen

With this understanding of the sources and losses

of oxygen and nitrogen in the closed circuit, oxygen
Closed-Circuit Anesthesia

179

can be conserved to a large extent. The following

checks are required before using the closed circuit:

1. The circuit should be tested for leaks. The

circuit should hold 40 cm H2O with an inflow of less than 200 mL/min.

2. The carbon dioxide absorbent should be

checked. With a double-canister system,

the absorbent should not be changed until

the indicator has begun to change color in

the lower canister. At this point, the bottom canister should be moved to the top

and a fresh canister placed in the bottom.

Changing canisters when the indicator has

changed in only the upper canister will

waste substantial amounts of soda lime.7

3. The function of the one-way valves should

be confirmed since incompetent valves may

allow rebreathing of carbon dioxide.

4. The oxygen analyzer, if available, should

be calibrated and the low-FIO2 alarm set.

During low-flow anesthesia, we wish to produce

a slight outward leak so that the FIO2 will not fall

during the case. A hanging bellows ventilator should

not be used. If ventilation is controlled, it should be

done either manually or with a rising-bellows ventilator. Any leaks will be outward so long as the

flows are adjusted to fill the bag or bellows at

the end of expiration. Flows of 250 to 350 mL/min

should be adequate. If the anesthesia provider

finds that larger flows are required to maintain

system volume, a search should be made for leaks.

Common sources of leaks include around the

face mask, around the endotracheal tube, and loose

fittings.

Most discussions of closed-circuit anesthesia have

emphasized the delivery of nitrous oxide.8,9 Several

of the steps required for the delivery of this relatively impotent anesthetic are no longer required

when it is eliminated. Thorough denitrogenation is

required if nitrous oxide is used, as any residual

nitrogen limits the amount of nitrous oxide that can

be given. When only oxygen is being administered,

the circuit can be closed after partial denitrogenation

(FIO2 of 0.4–0.5). With only outward leaks, the FIO2

will slowly increase during the case. An oxygen

analyzer is mandatory when nitrous oxide is a component of the anesthetic. When only oxygen is used,

continuous FIO2 monitoring is no longer essential.

In the field, oxygen analyzers may not be available

or may be in short supply. If available, the analyzers should probably be utilized intermittently to

conserve their function. A top priority for their use

is confirmation of the contents of newly opened

oxygen cylinders. Additionally, they may be helpful

to check the initial FIO2 and at intervals during the case

to assure that an inward leak has not developed.

POTENT VOLATILE ANESTHETIC AGENTS

Although intravenous agents will probably be

the mainstay in field anesthesia, occasions will arise

when supplementation with low doses of a potent

volatile agent would be desirable. The closed circuit can be used to deliver potent volatile agents

while conserving precious oxygen supplies. Closedcircuit administration of potent volatile agents requires a special pharmacokinetic conceptualization.

The intravenous line and the closed anesthetic

circuit are both extensions of the patient’s vasculature (Figure 8-3). When a drug is injected into the

intravenous line, it flows to the vasculature and is

distributed to body tissues. For purposes of this

chapter, dosageis defined as the amount of drug that

reaches the vasculature. Because little of the drug is

lost in the line, the dose is equivalent to the amount

injected. Strictly speaking, dosage should be expressed in moles; however, it is usually expressed

as mass (grams, milligrams, or micrograms), which

is the amount in moles multiplied by the molecular

weight.

Fig. 8-3. Like the intravenous (IV) line, the closed circuit

is an extension of the patient’s vasculature. O2: oxygen;

VO2: normal adult consumption of oxygen; a: carbon

dioxide absorbant.

IV

VO2

a

O2 Flow
Anesthesia and Perioperative Care of the Combat Casualty

180

time axis is transformed to SQRT, the plot becomes

linear with a slope equal to the unit dose (UD): Cumulative Dose (mL)

Dosage is defined similarly for volatile anesthetics. Provided that the anesthetic circuit is closed,

the fate of volatile agents is straightforward. After

it is injected into the circuit, the volatile anesthetic

vaporizes, enters the vasculature via the alveolar

capillary membrane, and is distributed to body

tissues. Except for the amount that primes the

circuit, all volatile agent injected into the circuit

reaches the patient’s vasculature. Therefore, dosage is clearly defined: it is the amount injected into

the circuit. Strictly, dosage of a volatile anesthetic

should also be expressed in moles; however, because each agent is a pure liquid with a constant

molarity, it is more convenient to express dosage as

milliliters of liquid, which is equal to the dosage in

moles multiplied by the molecular weight and divided by the density. Please note that the various

anesthetics vary in potency, molecular weight, and

density, so that liquid dosage requirements differ

between agents (ie, 1 mL of halothane is not the

same as 1 mL of isoflurane, just as 1 mg of fentanyl

is not the same as 1 mg of morphine).

If the circuit is not closed, the dosage is still the

amount of anesthetic that reaches the patient’s vasculature; however, this can no longer be conveniently measured because a large, unpredictable

amount escapes via the relief valve. Please note that

the concentration of volatile agent in the circuit is

not the dosage, just as the concentration of an intravenous anesthetic in the intravenous line is not the

dosage. In other words, when liquid volatile anesthetics are injected into a closed circuit, the dosage

the patient receives is the amount of liquid injected

into the closed circuit, just as the dosage of an

intravenous agent is the amount injected into the

intravenous line.

Pharmacokinetics

With dosage defined, the next question is: How

much volatile anesthetic should we give? Inhaled

anesthetics display square-root-of-time (SQRT) kinetics.10,11 When the cumulative dose (in milliliters

of liquid) of a potent inhalational anesthetic is plotted against time required to maintain a constant

blood concentration, a constant amount of anesthetic (unit dose) is seen to be absorbed in each

SQRT interval (0–1 min, 1–4 min, 4–9 min, 9–16 min,

etc) (Figure 8-4). These intervals increase in length

throughout the case. In the graph, the curve does

not pass through the origin because one additional

unit dose is required to prime the circuit. When the

Fig. 8-4. To maintain a constant blood concentration of

volatile liquid anesthetic, (a) cumulative dose of volatile

liquid anesthetic (in milliliters) is plotted against the

time required to maintain a constant blood concentration. (b) Cumulative dose vs. square root of time (SQRT)

yields a straight line.

where t represents elapsed time in minutes and TD

represents the cumulative (total) dose in milliliters

of liquid. The 1 added in the denominator accounts

for the circuit prime.

It is possible to utilize rigid dosage regimens

based on the model in which the patient receives a

predetermined unit dose at each SQRT interval (0

min, 1 min, 4 min, 9 min, 16 min, etc.). This would

be comparable to giving the same predetermined

dose of an intravenous agent, such as sodium

nitroprusside, fentanyl, or atracurium, to every

patient: dosage requirements vary among individual

patients; so, while a single infusion regimen treats

the average patient, it underdoses some and overdoses others. Dosage requirements for volatile anesthetics also vary among patients. Therefore, except in some experimental situations, it is prudent

to adjust administration based on patient response.

SQRT kinetics can be used to assess dosage requirements during anesthesia and to assist the anesthesia provider in adjusting the dose, based on

patient response. Figure 8-5 shows the curves obtained when cumulative dosage is plotted against

time for two individuals with different dosage re-

(1) UD = 1 + √t

TD

a

5 10 15 20 25

1

2

3

b

1 4 9 16 25

Time (min) (Time)1⁄2
Closed-Circuit Anesthesia

181

(2) f = =

quirements; when concentration is plotted against

SQRT, lines with different slopes are obtained. The

slopes of these lines are the respective unit doses for

the two patients.

In many areas of pharmacology, it is customary

to index dosage based on patient size. Weight and

body surface area (BSA) are two common measures.

Although BSA is usually derived from a nomogram

or formula involving height and weight, some physiologists believe that the weight expressed in kilograms, raised to the three-fourths power (kg3⁄4), is a

more precise parameter.12 In closed-circuit anesthesia, it has become customary to index dosage based

on this physiological BSA–weight relation. The dosage

index f represents the unit dose from equation 1 indexed for patient size using equations 2 and 3:

UD TD

(3) UD1 = m • kg3⁄4

The multiplier m in equation 3 accounts for differences in density, molecular weight, and potency

among the volatile anesthetics and is different for

each agent (Table 8-1). In an individual patient, a

given dosage index should provide the same depth

of anesthesia no matter which inhalational agent is

used. Cumulative Dose (mL)

UD1 UD1(1 + √t)

TABLE 8-1

MULTIPLIERS FOR CALCULATING UD1

The dosage index f can be used to compare dosage requirements between patients. Additionally,

since the dosage requirement for an individual patient remains fairly constant, the index guides administration while the patient is receiving the anesthetic. In theory, during a pure inhalational

anesthetic procedure, a dosage index of 1 should

prevent movement to skin incision in one half of

patients, and an index of 1.3 should prevent movement in 95% of patients.4 In practice, however,

various intravenous agents (eg, opioids, benzodiazepines, and muscle relaxants) are utilized, so the

required dosage index is much less.

Figure 8-6 shows a frequency distribution of the

dosage index f during a fentanyl/isoflurane/

pancuronium/oxygen anesthetic administered for

elective surgery in healthy adults.13 Note that the

mean dosage index was 0.42, with 46 of 52 (88%)

patients requiring a dosage index between 0.32 and

0.52. The required dosage index may be lower in

patients whose physical status is poor, or when large

amounts of intravenous medications are utilized. The

dosage requirement is also usually lower during surgical preparation when little stimulus is provided

and the effect of induction agents is still present.

Concentration and Dosage

The foregoing discussion of closed-circuit pharmacokinetics was prefaced by a careful definition of

dosage. Most anesthesia providers are more accustomed to thinking in terms of concentration of volatile anesthetics with semiclosed anesthesia systems.

A concentration-response curve (ie, a minimal alveolar concentration [MAC] assay) has become

widely used in conceptualizing inhalational anesthetic pharmacology.14 Because blood concentrations of volatile agents are difficult to measure, the

end-tidal concentration is utilized instead.15 As

Fig. 8-5. (a) Cumulative dose is plotted against time for

two individuals with different dosage requirements. (b)

When cumulative dose is plotted against the square root

of time (SQRT), two lines with different slopes are obtained. The slope equals the unit dose.

Anesthetic Multiplier

Halothane 0.029

Isoflurane 0.038

Enflurane 0.062

Diethylether 0.24

Time (min) (Time)1⁄2 1 + √t

a b
Anesthesia and Perioperative Care of the Combat Casualty

182

Fig. 8-6. Frequency distribution of dosage index f. Data

were extracted retrospectively from 52 anesthesia records

in which closed-circuit isoflurane/fentanyl/pancuronium/oxygen technique was utilized. All patients were

American Society of Anesthesia categories I and II and

were scheduled for elective orthopedic or gynecologic

surgery. Anesthesia was induced with thiopental (3–5

mg/kg). Tracheal intubation was facilitated with

succinylcholine or pancuronium. Maintenance muscle

relaxation was provided with pancuronium. The patients received fentanyl (150–250 μg) during the first

hour of anesthesia. After intubation, the circuit was closed

and isoflurane was administered by liquid injection,

guided by clinical signs of anesthesia. The dosage index

was recorded every 10 to 15 minutes on the anesthesia

records. The mean dosage index during the first hour of

surgical stimulation was extracted from each record;

these values were used to construct the frequency distribution. Reprinted with permission from Baumgarten RK,

Elms MK. Dosage requirements for closed circuit anesthesia. In: Bergmann H, Kramar H, Beiträge zur

Anaesthesiologie und Intensivmedizin. Vol 7. In: European

Congress of Anaesthesiology. Vienna, Austria: Verlag

Wilhelm Maudrich; 1986: 55. Abstract 107.

would be expected, the dose-response curve (Figure 8-7) for volatile anesthetics is very similar to the

MAC assay.

The Pharmacological Uncertainty Principle

With the proliferation of mass spectrometers now

being used in clinical anesthesia, many anesthesia

providers are now accustomed to adjusting the endtidal concentration to achieve the desired depth of

anesthesia. It might be attractive to measure both

dosage and end-tidal concentration during closedcircuit anesthesia; however, this is very difficult

Fig. 8-7. The data from Fig. 8-6 were used to construct this

dose-response curve for isoflurane. The frequency histogram is reexpressed as cumulative percentage versus the

natural logarithm of ƒ (ln ƒ).

with current equipment. Because one of the largest

leaks in anesthesia equipment is the gas removed

by a mass spectrometer, it is no longer possible to

assess dosage accurately. Therefore, we can either

know the dosage or the concentration but not both.

This is analogous to Heisenberg’s principle: one can

precisely measure the position or the momentum of

a subatomic particle, but not both. The advent of

stand-alone monitors that can return sampled gas

to the circuit should make it possible to measure

concentration and dosage simultaneously. This

may be very useful for teaching closed-circuit anesthesia.

With adult patients, leaks of 50 to 100 mL/min

are tolerable because the amount of agent lost in the

leak is small relative to the amount absorbed by the

patient. This is important, as small leaks are useful

to assure that any leak is outward. (With pediatric

patients, leaks are more serious because the amount

lost in even a small leak is significant compared

with the patient’s smaller dosage requirement.

When closed-circuit anesthesia is used with small

children, a tight-fitting face mask is necessary to

prevent leaks, and a tuberculin syringe is used to

deliver small, incremental doses of anesthetic agent

to the circuit.16

Equipment for Administering Volatile Agents

We have emphasized the importance of knowing

Number of Patients

Cumulative Percentage of Patients

20

10

15

5

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

ƒ

100

40

60

80

20

10

–1 0

ln ƒ

–2
Closed-Circuit Anesthesia

183

Fig. 8-8. Note the prominent label on this expedient

liquid injector. The large needle facilitates filling the

syringe and advertises that this is not a syringe intended

for intravenous injection. The syringe remains in the

circuit and is not placed with other syringes. If the syringe requires refilling, a new location in the tubing can

be used for reinsertion.

the dosage of volatile agent administered to the

patient. Although vaporizers can be used for closedcircuit anesthesia, they can also introduce some

complexity. When a vaporizer is used, molar dosage rate will depend on the vaporizer setting. To

obtain the cumulative dose, the anesthesia provider

must add all the various settings that have been

used and multiply by the time that each was used—

a cumbersome task. Liquid injection eliminates

these difficulties.11 The cumulative dose is readily

apparent by subtracting from the amount remaining in the syringe. Additionally, the molar dose is

the same at any ambient temperature and pressure,

as this only depends on the molecular weight and

the density of the liquid, which are constant. Molar

dosage does not depend on vapor pressure. This is

important because vapor pressure varies dramatically over the range of ambient pressures and temperatures in which field anesthesia may be practiced. The molar output of many vaporizers,

especially the copper kettle, increases substantially

with increasing temperature.17

In the case of in-circuit vaporizers, dosage rate

will also depend on the oxygen flow rate (see Figure

8-3). It may be difficult to assure the accuracy of

flowmeters in field medical treatment facilities. With

liquid injection, the dose does not depend on the

oxygen flow rate, just as the dose of an intravenous

agent will not depend on the intravenous flow rate.

It is vitally important to prevent accidental intravenous injection of liquid volatile anesthetic agents.

Prominent labeling is crucial. At one time, injection

ports were commercially available and the syringe

could be left in the port throughout the case18; however, the port was interchangeable with intravenous fitting so the potential for intravenous injection still existed. An injection port can also be

fabricated from a metal T-piece.9 An expedient

injector is pictured in Figure 8-8. A disposable

syringe is used with a long needle, either an 18-

gauge spinal needle or the introducer from a 16-

gauge intravenous cannula. The long needle facilitates drawing up the liquid anesthetic from the

bottle. The injector is inserted into the tubing, in

either the inspiratory or the expiratory limb, and

left in place. Therefore, it is very unlikely that it will

be interchanged with other syringes. The needle

never leaves the syringe and its length draws attention—the contents of this syringe are unusual and

not for intravenous injection. With disposable syringes, the plunger swells slightly on contact with

volatile agent so that it will not release agent into

the circuit without the plunger’s being purposefully pushed.

Square-Root-of-Time Kinetics for Intravenous Agents

Because the dosage concept (see Figure 8-3)

applies to both closed-circuit and intravenous

administration, it is quite possible that the pharmacokinetics of volatile and intravenous anesthetics

are quite similar. Intravenous agents are usually

described with linear multicompartmental models;

infusion schemes that produce constant blood

levels in these models have been described.19,20 These

schemes consist of an initial bolus followed by

an exponentially decreasing infusion. Using these

equations, the cumulative dose was plotted against

time for two typical intravenous agents, lidocaine21 and fentanyl22,23 (Figures 8-9 and 8-10). When

these curves are transformed to SQRT, an excellent
Anesthesia and Perioperative Care of the Combat Casualty

184

linear fit is achieved over the first 3 to 4 hours

of administration. Thus, the SQRT model may

also apply to intravenous agents. As anesthesia

providers become more comfortable with intravenous anesthesia based on adjusting dosage to

patient response, the generalization to dosagebased administration of volatile anesthetics may

become easier.

Fig. 8-10. (a) Cumulative dose of fentanyl plotted against time, from a pharmacokinetic simulation for a 70-kg subject with

a target concentration of 5 ng/mL. A three-compartment open model was used.(b) Cumulative dose of fentanyl plotted

against the square root of time (SQRT). The unit dose equals 156 μg. Data sources: (1) Alvis JM, Reves JG, Govier AV.

Computer assisted continuous infusions of fentanyl during cardiac anesthesia: comparison with a manual method.

Anesthesiology. 1985;63:41. (2) McClain DA, Hug CC. Intravenous fentanyl kinetics. Clin Pharmacol Ther. 1980;28:106–114.

400

600

800

200

0

Cumulative Lidocaine (mg)

0 100 200 300

Time (min)

800

600

400

200

0

y = 30 + 47x

R = 0.99

0 5 10 15

Square Root of Time

a b

0

500

1,000

1,500

2,000

2,500

0 50 100 150 200 250

Cumulative Fentanyl (μg)

1,500

1,000

2,500

2,000

500

0

Cumulative Fentanyl (μg)

Time (min) Square Root of Time

0 5 10 15

y = 35 + 156x

R = 1.00

Cumulative Lidocaine (mg)

a b

Fig. 8-9. (a) Cumulative dose of lidocaine is plotted against time, from a pharmacokinetic simulation with a target

concentration of 3 μg/mL. A two-compartment open model was used with an initial bolus followed by an exponentially decreasing infusion. (b) Cumulative dose of lidocaine plotted against the square root of time (SQRT). Note that

the slope of the line (ie, the unit dose) is 46 mg. Data source: Riddel JG, McCallister GB, Wilkinson GR. A new method

for constant plasma drug concentrations: Application to lidocaine. Ann Int Med. 1984;100:25–28.
Closed-Circuit Anesthesia

185

SUMMARY

Compressed oxygen will probably be in short

supply in many deployment situations. Nitrous

oxide will not be available at all. Simplicity and

ease of use are also important in difficult settings.

Therefore, the use of the closed circuit to provide a

high FIO2 during anesthesia is a valid and practical

approach to the management of casualties in field

medical treatment facilities. Closed-circuit delivery of anesthetic agents can be used as an adjunct to

intravenous techniques with which the anesthesia

provider is already familiar. This approach can

conserve limited supplies of compressed gas. Additionally, the pharmacokinetic analogy between

intravenous and potent volatile anesthetics may be

used to balance intravenous techniques with moderate doses of inhalational anesthetics.

REFERENCES

1. King M. Primary Anaesthesia. Oxford, England: Oxford University Press; 1986: 82.

2. Jowitt MD, Knight RJ. Anesthesia during the Falklands campaign: The land battles. Anaesthesia. 1983;38:776–783.

3. Waters, J. Commander, US Navy. Personal communication, October 1991.

4. Lowe HJ, Ernst EA. Uptake and distribution: Model development. In: The Quantitative Practice of Anesthesia: Use

of the Closed Circuit. Baltimore, Md: Williams & Wilkins; 1981: Chap 4: 58–60.

5. Nunn JF. Applied Respiratory Physiology. London, England: Butterworths; 1987: 366.

6. Lowe HJ, Ernst EA. Basic anesthetic concepts. In: The Quantitative Practice of Anesthesia: Use of the Closed Circuit.

Baltimore, Md: Williams & Wilkins; 1981: Chap 3: 47–50.

7. Dorsch JA, Dorsch SE. The Breathing System. IV. The Circle System. Understanding Anesthesia Equipment.

Construction, Care and Complications. Baltimore, Md: Williams & Wilkins; 1984: 210–246.

8. Lowe HJ, Ernst EA. The Quantitative Practice of Anesthesia: Use of the Closed Circuit. Baltimore, Md: Williams &

Wilkins; 1981: Chap 9: 153–173.

9. Kofke W, Andrew L, William B. Closed circuit anesthesia. In: Firestone LL, ed. Clinical Anesthesia Procedures of

the Massachusetts General Hospital. New York, NY: Little, Brown; 1988: Chap 14: 226–243.

10. Severinghouse JW. The rate of uptake of nitrous oxide in man. J Clin Invest. 1954;33:1183.

11. Lowe HJ, Ernst EA. Uptake and distribution: Square root of time model. In: The Quantitative Practice of Anesthesia:

Use of the Closed Circuit. Baltimore, Md: Williams & Wilkins; 1981: Chap 5: 67–97.

12. Brody S. Bioenergetics and Growth. New York, NY: Reinhold; 1945.

13. Baumgarten RK, Elms MK. Dosage requirements for closed circuit anesthesia. In: Bergmann H, Kramar H,

Beiträge zur Anaesthesiologie und Intensivmedizin. Vol 7. In: European Congress of Anaesthesiology. Vienna, Austria:

Verlag Wilhelm Maudrich; 1986: 55. Abstract 107.

14. Eger EI, II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: A standard of anesthetic

potency. Anesthesiology 1965;26:756–763.

15. Eger EI, II, Bahlman SH. Is end-tidal anesthetic partial pressure an accurate measure of the arterial anesthetic

partial pressure? Anesthesiology. 1971;35:301–303.

16. Couta da Silva JM, Tubino PJ, Vieira ZEG. Closed circuit anesthesia in infants and children. Anesth Analg.

1984;63:765–769.
Anesthesia and Perioperative Care of the Combat Casualty

186

17. Dorsch JA, Dorsch SE. Vaporizers. Understanding Anesthesia Equipment. Construction, Care and Com;ications.

Baltimore, Md: Williams & Wilkins; 1984: 77–135.

18. Lowe HJ, Ernst EA. Using volatile agents. In: The Quantitative Practice of Anesthesia: Use of the Closed Circuit.

Baltimore, Md: Williams & Wilkins; 1981: Chap 11: 183.

19. Krueger-Thiemer E. Continuous intravenous infusion and multi-compartment accumulation. Eur J Clin Pharmacol.

1968;4:317.

20. Schwilden H. A general method for calculating the dosage scheme in linear pharmacokinetics. Eur J Clin

Pharmacol. 1981;20:379.

21. Riddel JG, McCallister GB, Wilkinson GR. A new method for constant plasma drug concentrations: Application

to lidocaine. Ann Int Med. 1984;100:25–28.

22. Alvis JM, Reves JG, Govier AV. Computer assisted continuous infusions of fentanyl during cardiac anesthesia:

Comparison with a manual method. Anesthesiology. 1985;63:41.

23. McClain DA, Hug CC. Intravenous fentanyl kinetics. Clin Pharmacol Ther. 1980;28:106–114.
Inhalational Anesthesia

187

Chapter 9

INHALATIONAL ANESTHESIA

RICHARD B. HECKER, D.O.*

INTRODUCTION

OBSERVATIONS ON MECHANISMS OF ACTION

Lack of Structural Specificity

Cutoff Effect

Stereoselectivity

Pressure Reversal

HYPOTHESES OF INHALATIONAL ANESTHETIC ACTION

Lipid Hypotheses

Protein Hypothesis

Lipid–Protein Interaction Hypothesis

SITE OF ACTION

OVERVIEW: MODERN INHALATIONAL ANESTHETIC AGENTS

Halothane

Enflurane and Isoflurane

Desflurane

Sevoflurane

Nitrous Oxide

UPTAKE AND DISTRIBUTION

Biophysical Properties

Factors Affecting Uptake and Distribution

Minimal Alveolar Concentration

MAJOR ORGAN SYSTEM EFFECTS OF THE POTENT INHALED AGENTS

The Respiratory System and the Carbon Dioxide–Response Curve

The Central Nervous System

The Cardiovascular System

The Hepatic System

The Renal System

ANESTHESIA IN THE FIELD

SUMMARY

*Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Brooke Army Medical Center, Fort Sam Houston, Texas; Clinical

Assistant Professor of Anesthesiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7834,

and The Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799
Anesthesia and Perioperative Care of the Combat Casualty

188

INTRODUCTION

A variety of anesthetic agents may be administered by different routes to produce both unconsciousness and the absence of sensation to allow for

surgical procedures. Typically, general anesthesia

is accomplished by the inhalation of anesthetic gases,

and although drug administration by inhalation

may appear to be unusual, complicated, and awkward to most physicians, it is a familiar route of

drug delivery to all anesthesiologists. The pulmonary bed provides an excellent interface for controlling the delivery or removal of inhaled anesthetic

agents, oxygen, or carbon dioxide, and measuring

the alveolar partial pressure of gases allows for

precise control of the depth of anesthesia.

With the exception of nitrous oxide, the modern

inhalational anesthetic agents are volatile liquids

that are vaporized for administration. These agents

are potent, stable, storable for extended periods of

time, nonflammable, and useful in almost any surgical setting. Military anesthesia providers deployed with the U.S. Department of Defense’s

Deployable Medical Systems (DEPMEDS)–equipped

forward hospitals may find that the inhalational

anesthetic technique, not regional or other methods

that are commonly used in civilian hospitals, is the

one most often used.

OBSERVATIONS ON MECHANISMS OF ACTION

Although general inhalational anesthetics have

been employed for almost 150 years, an understanding of their interaction with organ systems

and structures to produce the anesthetic state has

not been well delineated. Modern research has

been focusing on structural changes in biological

membranes on exposure to anesthetic molecules,

but any theory of anesthetic action must take into

account the following observations that are related

to a state of narcosis1

:

• An extensive array of unrelated chemical

structures produce general anesthesia. They

do not share any common structure–activity relationship.

• During narcosis, alterations of function occur in all body systems. Physiological, metabolic, and structural changes occur that

must be rationalized and explained by an

organized system.

• The lipid solubility of anesthetics seems to

be important, as the wide range of effective

concentrations of agents is reduced to a

small range when lipid solubility is calculated and taken into account.

• The phenomenon of pressure reversal that is observed in general anesthesia must be explained by any mechanistic theory of anesthesia.

To expand on the above observations, a major

point in the study of the action of general anesthetics is that all the proposed theories have been based

on observations of anesthetic agents in living organisms. Based on these observations, and after

careful determinations of an anesthetic’s potency,

four specific pharmacological characteristics have

been described for an agent to be considered to have

the qualities of a true general anesthetic: (1) lack of

structural specificity, (2) cutoff effect of anesthetic

potency, (3) lack of stereoselectivity, and (4) demonstration of pressure reversal.

Lack of Structural Specificity

An amazing number of chemically different molecules cause general anesthesia. The implication of

this observation is that there is no single specific

receptor that mediates general anesthesia. Early in

this century, Hans H. Meyer and Charles E. Overton

each independently observed that anesthetic potency correlates well with an agent’s solubility in

the simple organic solvent, olive oil.2,3 This correlation of anesthetic potency with lipid solubility has

been termed the Meyer-Overton rule and is easily

demonstrated (Figure 9-1).4 The Meyer-Overton

rule can be interpreted to mean that the product of

an index of anesthetic potency and the agent’s solubility in a lipid is a constant, which, in theory,

should be the same for all inhalational agents. The

Meyer-Overton rule is usually taken to mean that

inhalational agents have their site of action in the

lipid component of cells. However, it is more correct to say that the site is nonpolar.

J. Ferguson proposed in 1939 that an anesthetic’s

potency can be expressed in terms of thermodynamic activity: whatever the concentration of a given

anesthetic agent required to produce a given level

of anesthesia, the thermodynamic activity would be
Inhalational Anesthesia

189

0

1

2

3

4

5

6

7

8

9

10

0 10 20 30 40 50 60 70 80 90 100 110

Fig. 9-1. These data, in which an inhalational anesthetic’s minimal alveolar concentration is plotted as a function of its

solubility in lecithin, are shown in a modern representation of the observations that led Meyer and Overton

individually to propose that anesthetic potency is related to lipid solubility. The curve has the mathematical form:

constant = XY. A straight line with a negative slope is obtained when the data are plotted using log-log coordinates.

Data source: Taheri S, Halsey MJ, Liu J, Eger EI II, Koblin DD, Laster MJ. What solvent best represents the site of action

of inhaled anesthetics in humans, rats, and dogs? Anesth Analg. 1991;72:Table 1, p 631; Table 4, p 632.

the same.5 The thermodynamic activity of a volatile

agent (which, for purposes of this chapter, can be

considered its vapor pressure) is a property of the

anesthetic molecule. Ferguson’s rule can be interpreted to mean that the quotient of (a) the partial

pressure of an anesthetic agent at which one half of

the subjects are anesthetized, and (b) the vapor

pressure of the agent at the appropriate temperature is a constant that, in theory, should be the same

for all inhalational agents. Ferguson’s rule is silent

as to the anesthetic’s site of action.

The rules of Meyer-Overton and Ferguson both

have notable exceptions that provide insight into

the mechanisms by which inhalational anesthetics

act. Both exaggerate the potency of hydrogen and

certain inert gases such as helium and neon, while

the Ferguson rule also underestimates the anesthetic potency of short-chained fluorocarbons. The

failure to predict the anesthetic potential of low-molecular-weight gases is now recognized to be a consequence of the phenomenon of pressure reversal.6

Cutoff Effect

In 1939, when he was studying homologous series of primary alcohols, Ferguson noted that carbon chained compounds demonstrate an anesthetic

cutoff effect.5 Beginning with methanol (CN=1), anesthetic potency increases logarithmically with the addition of carbon atoms until the effect abruptly stops,

and further addition of carbon moieties not only does

not enhance potency, but such molecules are devoid

of anesthetic potential. In the first series studied,

potency ended at CN=12. This was termed the cutoff

effect. When other homologous series were studied,

both the type of bonds in the compound and the

addition of other radicals attached to the first carbon were found to alter the absolute number of

carbon atoms required for anesthetic cutoff. Interestingly, the fully fluorinated alkanes demonstrate cutoff at a very short carbon length: at octafluropropane

(C3F8).7 The cutoff effect may have implications regarding the molecular binding site of anesthetics.

Lecithin-Gas Partition Coefficient

Solubility

Minimal Alveolar Concentration (% atm)

Halothane

Cyclopropane

Desflurane

Fluroxene

Sevoflurane

Enflurane

Isoflurane
Anesthesia and Perioperative Care of the Combat Casualty

190

It has generally been assumed that the cutoff

effect results from the failure of anesthetic agents

with large molecular dimensions to dissolve at the

site of action in a concentration sufficient to cause

an effect. This explanation is now known to be

untenable, at least for highly lipophilic alcohols

with more than 12 carbon atoms.6

Stereoselectivity

In general, anesthetics do not exhibit stereoselective effects. For example, both D-halothane

and L-halothane, when inhaled, inhibit synaptic

transmission and cause a disordered spin-labeling

of the bilipid membrane.8 Interestingly, the optical

isomers of isoflurane have markedly different effects on the nicotinic acetylcholine receptors of isolated neurons, even though their bulk lipid solubilities are identical.9 Although such findings suggest

that an agonist–receptor interaction could mediate

the effects of certain inhalational agents, the lack of

stereospecificity for inhalational agents, when assessed as general anesthetics, speaks against such a

phenomenon’s importance.

Pressure Reversal

The phenomenon of an anesthetic action’s being

reversed by the application of high pressure was

described in 1951 in tadpoles and confirmed later

in other species.10,11 One possible explanation for

pressure reversal is that it is an artifact caused

by the helium gas that is used to raise atmospheric pressure in these studies. Helium itself is

now known to be an anesthetic agent but has such

limited lipid solubility that anesthesia is seen

only at the very high pressures that are associated

with pressure reversal.12 It is now accepted that

pressure reversal is caused by ambient pressure

acting on specific anesthetic sites of action in the

lipid bilayer that constitutes the membrane of excitable cells. The mechanism is unclear but was originally thought to be due to the direct hydrostatic

compression of the dissolved anesthetic agent; this

smaller volume lessens the perturbation of the

lipid bilayer in proximity to ion channels. Not all

ion channels show pressure reversal—the nicotinic

acetylcholine receptor, for example, does not13—

and even more interestingly, pressure reversal is

seen only in species in which the amino acid glycine

functions as a neurotransmitter.14 The latter observations strongly suggest that pressure acts on

specific receptors rather than causing a generalized effect (eg, the compression of dissolved gas to

a critical volume that is unable to affect the structure of ionic channels).

HYPOTHESES OF INHALATIONAL ANESTHETIC ACTION

Determining the mechanisms of action of inhalational anesthetic agents is one of the most difficult

problems facing neuropharmacology. Based on the

aforementioned observations, prevailing hypotheses as to the modes of action fall into the categories

of lipid, protein, and lipid–protein interaction

(Figure 9-2).

Lipid Hypotheses

Both Meyer and Overton pursued their lipid hypotheses of anesthetic action without the benefit of

our current understanding of the phospholipid bilayer structure of cell membranes. They used olive

oil as a surrogate for a biological lipid, although,

interestingly, Meyer proposed that the biologically

important lipid in which inhalational anesthetics

exert their effect is the phosphocholine lecithin,

which we now know is an important constituent of

myelin sheaths. The simple dissolving of the anesthetic agent throughout the lipid-containing portion of the cell can no longer be viewed as a tenable

hypothesis: there is no obvious mechanism through

which the bulk presence of the agent can alter the

function of ionic channels, which mediate the excitability of cells. Although it might seem possible

that the presence of dissolved inhalational agent, by

swelling or expanding the membrane (Figure 9-2a),

might sufficiently distort the function of ionic channels, measured changes in the thickness of cell membranes due to the presence of an inhalational agent

are surprisingly small: from 0.15% to 0.36%.15–17

Attempts have been made to refine the lipid

membrane–expansion hypothesis by assuming that

the action of the inhalational agents is actually

localized to discrete sites within the cell membrane,

where a local change in the physical properties of

the phospholipid bilayer affects ionic channels responsible for anesthesia. The “lipid–phase-transition”14 and “membrane-disordering”18 hypotheses

are the best-known formulations that employ this

approach.

The lipid–phase-transition hypothesis proposes

that the lipid moiety of the lipid bilayer that is in

proximity to ionic channels exists in two phases: the

first consisting of liquid, low-density crystals; the
Inhalational Anesthesia

191

The membrane-disordering hypothesis. The presence of an inhalational

agent breaks up the normally parallel

arrangement of lipid molecules. In an

unknown manner, this perturbation

prevents the ionic channel from opening.

The phase-separation hypothesis. The

lipid within the cell membrane is assumed to exist in two physical states:

as a tightly packed gel and as loosely

packed liquid crystals. When the ionic

channel opens, neighboring liquid

crystals are converted to gel. The presence of an inhalational agent prevents

this phase transition, thereby inhibiting the opening of the channel.

The membrane-expansion hypothesis.

The inhalational agent so distorts the

membrane that the ionic channel cannot open.

a

b

c

d

The lipid–protein interaction hypothesis. Normal functioning of an ionic

channel depends on contact with lipid

molecules. The inhalational agent affects the lipid so that this relationship

is broken.

e

Fig. 9-2. A highly schematic and speculative rendering of hypotheses that purport to show possible mechanisms by

which inhalational anesthetic agents might cause anesthesia. The crucial assumption is that the agent interferes with

the normal function of neuroexcitatory cells. In each of the five sets of diagrams, membrane lipid is shown in yellow;

ionic channels in cell membranes are shown in blue; and inhalational agent is shown in red. Each figure shows the ionic

channel’s resting state (left); the bifurcating arrows indicate the transition to the active state (right), with the ionic

channel open (upper) and the state caused by the anesthetic agent (lower).

The protein hypothesis. The inhalational agent activates a receptor on a

protein which is a constituent of an

ionic channel causing it to open.

Viewed in terms of this hypothesis,

the correlation between lipid solubility and anesthetic potency is epiphenomenal.
Anesthesia and Perioperative Care of the Combat Casualty

192

second, a solid, high-density gel. Opening of the

ionic channel pushes aside the neighboring liquid

crystals, which then undergo a transition to the

more tightly packed gel phase (Figure 9-2b). The

presence of the dissolved inhalational agent is

thought to prevent this transition. This hypothesis,

however, finds little experimental support.

The membrane-disordering hypothesis is derived

from spectroscopic evidence that the normal parallel orientation of fatty acid chains of lipid molecules

in the cell membrane is disordered by the presence

of an inhalational agent (Figure 9-2c). The disordering effect of inhalational agents is seen only when

the membrane contains cholesterol in an amount

equal to the phospholipid component—an important observation.19 The membrane-disordering hypothesis assumes that the disorder introduced into

the membrane in some unknown way interferes

with the function of ionic channels. How and why

this happens remain to be determined, but two of

the phenomena that must be understood for a putative theory of inhalational agents to have face validity find explanation in the membrane-disordering

hypothesis:

1. Pressure reversal is seen to result from the

pressure-induced decrease in the random

molecular motion of the fatty acid chains

that comprise the central portion of the

membrane lipids. This ordering of the

membrane components reverses the disordering caused by the dissolved inhalational

agent.20

2. The cutoff phenomenon may be related

not to the inability of high-molecularweight agents to dissolve in the lipid membranes in a concentration that would cause

anesthesia, but from their failure to disrupt or disorder the architecture of the

lipid bilayer.6

Protein Hypothesis

Although the affinity of inhalational anesthetic

agents for lipids is commonly used as evidence that

their site of action must be in lipids, the term “lipid

solubility” actually refers to their solubility in nonpolar or hydrophobic media. Many proteins have

nonpolar regions that could serve as sites for the

dissolving of inhalational agents.21 However, these

regions are usually centrally located within the

protein and, therefore, are effectively shielded from

the action of all but pharmacological concentrations

of inhalational agents. Such unlikely, nonspecific

interactions of proteins and inhalational agents are

to be distinguished from interactions of great specificity (eg, those that occur between receptor and

agonist). There is no question that inhalational

anesthetic agents are capable of specific interactions with proteins22 (Figure 9-2d):

• Nicotinic acetylcholine receptors are inhibited by halothane, isoflurane, and methoxyflurane at minimal alveolar concentrations (MAC, which is discussed later in this

chapter), the end-alveolar concentration of

an inhalational anesthetic agent that prevents somatic response to a painful stimulus in 50% of individuals.

• γ-Aminobutyric acid (GABA) receptors are

activated by halothane and isoflurane at

MAC concentrations.

• The calcium-release channel of the sarcoplasmic reticulum in skeletal muscle is activated by halothane.23

• Chemoluminescence liberated by the action of the firefly enzyme D-luciferase is

inhibited by inhalational agents.24

The question is not so much whether inhalational

agents can affect proteins—they can—but whether

these effects are necessary for the induction of general anesthesia. Much needs to be known before

this question can be answered. For example, is

either (a) the inhibition of the nicotinic acetylcholine receptor or (b) the activation of the GABA

receptor a necessary concomitant for anesthesia? In

genetically predetermined individuals, intracellular calcium release by halothane is a profoundly

important clinical problem but in normal people is

trivial. The inhibition of chemoluminescence by

inhalational agents is well described, but there is no

evidence that a mammalian equivalent exists. It is

perhaps best to defer judgment as to the importance

of the protein hypothesis until more data have been

collected and reviewed.

Lipid–Protein Interaction Hypothesis

The evidence supporting the protein hypothesis

was derived from lipid-free systems. Since

biomembranes are aggregates of lipoproteins, it

is appropriate to ask whether inhalational agents

produce anesthesia by affecting lipoproteins or

those lipids in direct contact with proteins of the

ionic channel (Figure 9-2e). The lipids that are in

direct association with the transmembrane-receptor proteins are known as the boundary lipids.25
Inhalational Anesthesia

193

Current research is centered on trying to establish

whether inhalational anesthetic–induced perturbation of boundary lipids can be coupled selectively

to ionic channels, causing protein conformational

changes.26

Knowledge of the mechanism of action of inhalational anesthetics has practical importance, because

it furthers the process of designing new agents.

Nevertheless, it is apparent that a given agent may

have a multitude of effects, some of which may be

unrelated to the induction of a state of general

anesthesia. Even the induction of general anesthesia can be mediated by several mechanisms. For

example, inhalational anesthetics fall into two broad

classes: alkanes and ethers. Cyclopropane and

halothane are alkanes; diethyl ether, enflurane,

isoflurane, desflurane, and sevoflurane are ethers.

The alkanes are purely lipophilic and therefore dissolve primarily in the lipid portion of the cell membrane, where they exert a nonspecific effect. The

halogenated ethers, being more polar, both dissolve

in the lipid membrane and form hydrogen bonds

with protein moieties of ionic channels. Thus, the

ether anesthetics are capable of both specific and

nonspecific interactions. It is likely that the stereospecificity of the optical isomers of isoflurane

arises from the ability of only one isomer to form

hydrogen bonds with receptor proteins.

SITE OF ACTION

A large body of work has been directed toward

locating the major areas of interaction within the

central nervous system (CNS) that are influenced

by the anesthetic agents. It is now obvious that

anesthetics do not exert their action through one

specific effect in any one particular region of the

CNS. Based on this information, more recent work

has been directed at the cellular rather than the

regional level of the CNS. One early and consistent

observation has been that general anesthetic agents

block neural transmission at the synapse at much

lower concentrations than the concentrations required to block conductance within the axon. Based

on this information, the synapse has been the focus

of most recent studies. Because synapses are either

excitatory or inhibitory in nature, general anesthetic agents should have a depressant effect on

excitatory postsynaptic potentials (EPSPs), an augmentation of inhibitory postsynaptic potentials

(IPSPs), or both. It should be appreciated, however,

that synaptic transmission can be subdivided into

four areas for further study:

1. axonal conductance along the afferent

axon,

2. neurotransmitter release into the synaptic

cleft,

3. binding of the neurotransmitter by specific receptors in the postjunctional area,

and

4. changes in conductance, leading to propagation of the action potential.

When both the CNS and the peripheral nervous

system have been studied, the general anesthetic

agents do have a depressant effect on EPSPs, although the magnitude of effect on EPSPs is diverse

within the area of the hippocampus. These findings

suggest that either (a) EPSPs do not play a major

role in the action of anesthetic agents or (b) the

hippocampus is not relevant to general anesthetic

action.27

The principal inhibitory neurotransmitter within

the CNS is GABA. The data regarding general

anesthetic action on IPSPs are conflicting, especially information suggesting that halothane and

isoflurane cause a reduction in IPSPs. This phenomenon has been explained as an indirect action

due to a depression of excitatory synapses acting on

GABA-ergic inhibitory cells.28 More work is necessary to elucidate the role of inhibitory monosynapses

in the absence of excitatory synapse transmission.

To summarize, the synapse is probably the cellular site of action of the general anesthetic agents,

based on the low concentrations needed to affect

transmission. What is not understood is exactly

how these agents work at this level, as there is not

an anesthetic effect that is common to all synapses

or, indeed, to all anesthetic agents that have been

studied. Based on all available information, two

main theories have been promulgated to explain

anesthetic action at the synaptic level. The unitary

theory holds that all general anesthetic agents work

by a common mechanism. A more robust, conflicting theory called the degenerate theory holds that

different general anesthetic agents have different

mechanisms of actions at possibly different sites of

action. Two strategies attempt to elucidate information surrounding the degenerate theory: the pharmacological approach studies relative potencies of

anesthetic agents in animals, while the mechanistic

approach looks at well-defined molecular models

in an attempt to discover a yet-unknown site of

action in the CNS.
Anesthesia and Perioperative Care of the Combat Casualty

194

OVERVIEW: MODERN INHALATIONAL ANESTHETIC AGENTS

During the 1920s, the frustrations encountered in

clinical practice (eg, difficulties with the older inhalational agents in delivery, side effects, and flammability) coupled with an understanding of the

expanding scientific basis for anesthesia and surgery mandated that newer anesthetic agents be

developed to replace ether and chloroform. A variety of carbon-chain–based agents were studied and

marketed, and cyclopropane became the most important new inhaled anesthetic introduced in the

1930s. Prior to the 1950s, all inhalational anesthetic

agents possessed one or both of these two defects:

they were explosive, and they were toxic to biological tissues. Fortuitously, research in other fields

made possible the development and production of

fluorinated carbon-based anesthetic agents, which

are both biologically safe and nonexplosive.

A vast increase in our knowledge of the chemistry of elemental fluorine occurred during World

War II as a byproduct of the Manhattan Project. A

crucial step in the fabrication of the first atomic

bombs was the separation of the naturally fissionable isotope of uranium, 235U, from the much more

common 238U. The separation depended on the

availability of uranium hexafluoride, and the ability to synthesize and manipulate this unusual substance safely led to a better understanding of fluorine chemistry. The mass manufacturing of

fluorinated carbon-based compounds could then

follow. The addition of a fluorine molecule to

carbon was associated with decreased flammability. The fluorine–carbon bond was more stable than

the carbon–carbon bond, tended to undergo less

biological metabolism, and was therefore associated with less organ toxicity. The fluorinated anesthetic compound first marketed was fluroxene,

which was introduced in 1954 and used until 1975.

Although fluroxene had the desirable qualities

of low solubility in blood and minimal tendency

to depress cardiovascular function, it was associated with nausea and vomiting and was flammable at higher concentrations. After a large experience with fluroxene had been collected, this

compound was found to be rarely associated with

hepatotoxicity and possible carcinogenesis.

Fluroxene was an important bridging compound in

inhalational anesthetic practice until the development and clinical introduction of safer and more

desirable agents.

Fluorinated compounds are today’s anesthetic

agents of choice (Table 9-1). The ones most commonly

used are halothane, enflurane, isoflurane,

and desflurane; sevoflurane was added to the

armamentarium in 1995. Nitrous oxide is neither

fluorinated nor available in DEPMEDS-equipped

hospitals but is included for the sake of completeness.

Halothane

F C C

Br

H

Cl

F

F

Halothane (1,1,1-trifluoro-2-bromo-2-chloro- Halothane

ethane) is an aliphatic hydrocarbon of the alkane

series (specifically, a halogenated ethane) that was

introduced into the clinical practice of anesthesia

in 1956. This important compound was a tremendous improvement over the earlier alkanes and

ethers and still has a role in civilian and military

anesthesia. The agent is somewhat unstable in the

presence of physical factors associated with the

delivery of anesthesia, and due to its spontaneous

oxidation and affinity for breakdown by ultraviolet

light must be stabilized with 0.01% thymol and

stored in dark brown bottles. In current practice,

halothane’s main drawbacks are its propensity to

sensitize the myocardium to the effects of epinephrine and its association with a metabolic-related

hepatotoxicity.

Halothane is well known to conventionally

trained anesthesiologists and continues to be a

very useful inhalational anesthetic agent—although

its use in the United States is much less than that

of the inhalational ethers. Halothane enjoys a

greater potency and has less airway irritability than

the newer halogenated ether agents and, therefore,

is better tolerated when a straight inhalational

induction technique is employed. Owing to its

association with a metabolic-related hepatotoxicity, halothane has been used as an induction agent

in adults and then discontinued and replaced by

one of the halogenated ether agents. A main disadvantage of halothane is its effect on the myocardium—from both a dose-related myocardial depression, which causes hypotension, and the

enhanced sensitizing effect it has with circulating

and administered catecholamines. Cerebral blood

flow (CBF) increases with halothane (due to its
Inhalational Anesthesia

195

TABLE 9-1

GENERAL PROPERTIES OF INHALATIONAL ANESTHETICS

Property N2O ISO ENF HAL DES SEV

Molecular weight 44 184.5 184.5 197.4 168 218

Boiling point (°C) –88.5 48.5 56.5 50.2 23.5 58.5

Specific gravity (25°C)* 1.53 1.5 1.52 1.86 1.45 1.50

Vapor pressure (20°C) (mm Hg) 38,770 238 172 243 664 160

(gas)

MAC (in O2) (%) 105 1.28 1.58 0.75 4.6–6 1.71

MAC (in 70% N2O) (%) — 0.56 0.57 0.29 0.66

AD95 — 1.68 1.88 0.90 2.07

MAC-awake (multiple) 0.6–0.8 0.52 0.53

MAC as partial pressure (mm Hg) 800 9.7 12.0 5.7 34.9–45.6 13.0

Partition coefficients (37°C)

Blood–gas 0.47 1.4 1.8 2.3 0.42 0.59

Brain–blood 1.1 2.6 1.4 2.9 1.3 1.7

Muscle–blood 1.2 4.0 1.7 3.5 2.0 3.1

Fat–blood 2.3 45 36 60 27 48

Rubber–gas 1.2 62 74 120 20 30

Flammability

(in 70% N2O/ 30%O2) (%) 7 5.8 4.8 17 10

Stability

Alkali Stable Stable Stable Some Stable Very unstable

instability

Ultraviolet Stable Stable Stable Unstable

Metal Stable Stable Stable Corrodes Stable Stable

Preservative None None None Thymol None None

Recovered as metabolites (%) 0.0 0.2 2.4 20

N2O: Nitrous oxide; ISO: Isoflurane; ENF: Enflurane; HAL: Halothane; DES: Desflurane; SEV: Sevoflurane; MAC: minimal alveolar

concentration; AD95: anesthetic depth (the dose that prevents movement in 95% of subjects in response to standard surgical incision) *Specific gravity for N2O is for the gas relative to air, but for the other anesthetics is for the liquid relative to water

Reprinted with permission from Longnecker DE, Miller FL. Pharmacology of inhalational anesthetics. In: Rogers MC, Tinker JH,

Covino BG, Longnecker DE. Principles and Practice of Anesthesiology. St. Louis, Mo: Mosby–Year Book; 1993: 1054.

vasodilating properties), and the potential exists for

an increase in intracranial pressure (ICP) that may

only be partially responsive to the elimination of

carbon dioxide via hyperventilation. Halothane also

causes an important decrease in splanchnic circulation and decreased total hepatic circulation, with

portal venous and hepatic arterial blood-flow decrements that may place the patient at risk for hepatic ischemia and hepatocellular tissue hypoxia.

The major route of elimination is via the pulmonary

bed, but up to 20% of halothane may be biotransformed in the liver. A combination of decreased

hepatic blood flow, major hepatic biotransformation, and a possible immunologically mediated

tissue injury may contribute to the hepatotoxicity seen in a small number (1:10,000) of adult

patients exposed to halothane. This incidence is

even lower in children. All the potent volatile

agents are associated with a dose-related, musclerelaxation effect.
Anesthesia and Perioperative Care of the Combat Casualty

196

Enflurane and Isoflurane

The ethers enflurane (1,1,2-trifluoro-2-chloroethyl

difluoromethyl ether) and isoflurane (1-chloro-2,2,2-

trifluoroethyl difluoromethyl ether) are isomers.

They share the same chemical formulae and molecular weight but differ in their physical and pharmacological properties owing to the position of the

carbon atom to which hydrogen and chlorine are

attached. These methyl-ethyl ethers are synthesized when bromine is removed from the halothane

molecule and an ether link, with a difluoromethyl

group attached, is created. The substitution of

fluorine for chlorine and bromine increases molecular stability while reducing potency and solubility. The alkanes (eg, halothane) appear to be

associated with cardiac toxicity, due to their ability

to sensitize the myocardium to catecholamines. The

interposition of oxygen in an ether linkage within

an anesthetic molecule reduces this myocardial irritability.

Enflurane

lar–arterial gradient that is greater than that seen

with halothane.31,32 Enflurane has been associated

with tonic-clonic muscle activity and confirmed

electroencephalographic (EEG) evidence of seizure

activity at higher doses, especially in the setting of

hypocarbia, although at lower doses it does not

appear to predispose patients with epilepsy to further seizure activity.33 The major route of elimination is via the lungs, with 2% to 3% being biotransformed in the liver. Major metabolic byproducts of concern include fluoride ions and

difluoromethoxydifluoroacetic acid.34 Because

nephrotoxicity has been associated with the fluoride ion by-product during very prolonged use,

many anesthesiologists prefer to avoid enflurane in

patients with renal compromise. The level of fluoride ion that is required to produce nephrotoxicity

(40–50 μmol/L) is rarely exceeded except during

dramatically prolonged enflurane anesthesia.27

Isoflurane

H CO CH C

F

F F

F

F

Cl

Enflurane was the first of the modern haloge- Enflurane

nated ether inhalational agents to be released for

clinical use (in 1972). Its principal advantage over

halothane is its reduced association with hepatotoxicity and catecholamine-induced myocardial irritability. Enflurane is approximately one half as

potent as halothane but can still provide prompt

induction of anesthesia. Like halothane, enflurane

causes a dose-related decrease in blood pressure

that makes this drug difficult to titrate between

adequate depth of anesthesia and unacceptable

hypotension.29 The dose-related hypotension is due

to a combination of myocardial depression and

peripheral vasodilation with decreased systemic

vascular resistance (SVR). As does halothane,

enflurane causes increased CBF and the potential

exists for increased ICP and cerebral hypoxia. Although total hepatic blood flow is decreased during

enflurane anesthesia, the relation between hepatic

arterial and portal blood flow remains preserved.30

Enflurane produces a dose-dependent respiratory

depression, hypercarbia, and an increased alveoF C

F

C

F

H

Cl

O C

F

F

H

Isoflurane, released for clinical use in 1981, is ISOFLURANE

probably the most popular potent volatile anesthetic agent currently administered in the United

States. Its major advantages include its ease of

administration, lack of serious hepatotoxicity, and

minimal biotransformation with fluoride ion

production. As with all of the volatile vapors,

it is a potent respiratory depressant and, although

isoflurane can be used to induce anesthesia,

some patients have complained of respiratory discomfort on inhalational induction. Isoflurane preserves cardiac output throughout all levels of anesthesia better than either halothane or enflurane

(Figure 9-3).

Isoflurane is associated with a dose-dependent

hypotension without myocardial depression that

is solely mediated by a decrease in SVR. This

vasodilating effect can actually be exploited when

a relatively hypotensive anesthetic technique is

desirable. Tachycardia is a commonly seen event

with isoflurane and appears more frequently with

younger patients.35 There does not appear to be

any appreciable myocardial irritability with circulating catecholamines during the use of isoflurane,
Inhalational Anesthesia

197

F C

F

F

C

H

F

O C

F

F

H

Desflurane

Fig. 9-3. Cardiac output is best preserved in

humans by isoflurane, compared with

halothane and enflurane. HAL: halothane;

ISO: isoflurane; ENF: enflurane. Reprinted

with permission from Longnecker DE, Miller

FL. Pharmacology of inhalational anesthetics. In: Rogers MC, Tinker JH, Covino BG,

Longnecker DE. Principles and Practice of

Anesthesiology. St. Louis, Mo: Mosby–Year

Book; 1993: 1073.

and although the phenomenon of coronary steal is

theoretically possible, it is infrequently observed.

Again, as with halothane, CBF increases. Although

isoflurane may cause an increase in ICP, this effect

can be totally abolished with hypocarbia.36 Previously, isoflurane had been thought to have less

effect on cerebral circulation than halothane,

but the effect may, in fact, be the same.30,37 Evidence from studies with animals indicates that

isoflurane offers better cerebral protection from

ischemia or hypoxia when compared with the

other volatile agents, and anesthesiologists who

provide care for neurosurgical procedures may

therefore consider isoflurane to be the potent

volatile agent of choice.38 There is a reduction

of total hepatic blood flow seen with isoflurane;

however, total flow, hepatic oxygen transport, hepatic oxygenation, and arterial compensation for

reduced portal flow are all better maintained with

isoflurane than with either halothane or enflurane.30,39,40 Hepatic injury has not been associated

with isoflurane, and this may be related to the

protective mechanisms mentioned above. Renal

blood flow is decreased under isoflurane administration, but this appears to be a function of decreased total perfusion rather than changes in regional vascular resistance.41 Isoflurane is excreted

via the lungs, and only 0.2% of the agent undergoes

biotransformation. The biotransformation of

isoflurane is only 1% of that of halothane and 10% of

that of enflurane, with the fluoride and trifluoroacetic acid metabolites being insufficient to

be associated with significant cellular injury or toxicity.42 The major complications associated with

isoflurane are related to the spectrum of its pharmacological activity (eg, hypotension, tachycardia,

hypercarbia) rather than to any specific organ toxicity per se. Indeed, the major advantage of

isoflurane is its rather remarkable lack of significant complications or evidence of associated hepatic toxicity. Isoflurane is a major inhalational

agent available to the military anesthesiologist in

the field.

Desflurane

Desflurane (1-fluoro-2,2,2-trifluoroethyl difluoromethyl ether) is a fluorinated methyl-ethyl ether in

which the chlorine has been totally removed from

the molecule. The lower solubility and chemical

stability afforded by this fluorine substitution is at

the cost of lower potency and a very high vapor

pressure: 664 mm Hg at 20°C. A special vaporizer

is required to deliver this agent. Although desflurane may prove to be a valuable agent in the

civilian setting because it allows for rapid emergence from anesthesia, the need for a special vaporizer makes it highly unlikely that this agent will be

used in the military field setting.

Cardiac Output (% Awake Value)

Minimal Alveolar Concentration
Anesthesia and Perioperative Care of the Combat Casualty

198

Introduced into clinical practice in 1992,

desflurane has the lowest solubility in blood of any

of the inhalational agents. Owing to its physical

property of a low blood–gas partition coefficient

(0.42), its main clinical advantage appears to be a

rapid emergence from anesthesia. Its main disadvantages are airway irritation, which limits its use

as an induction agent, and its physical property of

a high vapor pressure (desflurane boils at room

temperature), which requires a specially constructed

vaporizer to allow for its delivery in ordinary operating room settings. The circulatory and cerebral

effects of desflurane are identical to those seen with

isoflurane.43,44 The route of excretion is via the

lungs, and the biotransformation of desflurane is

trivial. Trifluoroacetic acid production is slight

(0.17 μmol/L), and is 10% of that seen with

isoflurane.27 The desflurane molecule is extremely

stable.

Sevoflurane

H C

C

O

C

F

F

F

F

F F

C

F

H

H

Sevoflurane

Sevoflurane (1,1,1,3,3,3-hexafluoro-2-propyl

fluoroethyl ether) is another highly fluorine-substituted structural modification of the ether link. In

this situation, the oxygen is located between an

ethyl and a propyl group, which allows for low

solubility. The addition of the propyl side chain

increases the agent’s potency.

Sevoflurane is the newest halogenated ether anesthetic agent and was released for clinical use in

the United States in 1995. Due to its low blood–gas

partition coefficient (0.59), sevoflurane has the advantage of rapid induction and emergence from

anesthesia. The cardiovascular effects of sevoflurane

appear to be similar to those of isoflurane.45,46 The

respiratory depression seen with sevoflurane is

significant but less than that seen with halothane. Changes in tidal volume and respiratory

excursion are greater with sevoflurane than with

isoflurane, and this suggests a neural control response to sevoflurane different from that seen with

isoflurane.47 The route of excretion is via the lungs

but the biotransformation of sevoflurane is very

significant: up to 10% of patients undergoing

sevoflurane anesthesia have plasma fluoride levels

that exceed 50 μmol/L, which is considered to be

the threshold for renal toxicity.48 Thus, a major

disadvantage of sevoflurane is that it may be limited to use for short procedures to avoid potential

renal damage, although prolonged sevoflurane anesthesia (9.5 MAC-hours) has been reported not to

impair renal concentrating function on days 1 and 5

after anesthesia.49 Finally, sevoflurane is very unstable in alkali and may not be suitable in situations

where low fresh-gas-flow states are needed, such as

the military setting, where gas supplies must be

conserved and strict economy of available resources

preserved.

Nitrous Oxide

NNO

In passing, it should be noted that the old standby NITROUS OXIDE

inhalational agent of the past—nitrous oxide—is

not fielded with DEPMEDS equipment and will

only be available in fixed military medical treatment facilities. Although nitrous oxide can successfully be coadministered with other inhalational

anesthetic agents, it must be stored in bulky gas

cylinders, it supports combustion almost as well as

oxygen, and it is subject to contamination from

other oxides of nitrogen that may be toxic, owing to

the production of free radicals. Because of weight

and storage constraints, and especially because it

expands in closed spaces, nitrous oxide will probably not be available to military anesthesia providers in the field.

Although nitrous oxide can be used by itself as

an analgesic agent for minor surgical procedures,

it is rarely used as a sole agent in modern anesthetic practice: its lack of potency and its MAC of

105% make it impossible to use as a total anesthetic

agent. Nitrous oxide is employed mainly to minimize the total dose of other potent volatile anesthetic agents by taking advantage of the additive property of MAC. Owing to its physical properties, nitrous oxide exhibits both the second-gas

and the concentration effects, which are discussed

later in this chapter. Nitrous oxide demonstrates

a mild increase in sympathetic nervous system

activity that may be matched by a mild myocardial depressant effect. By itself, nitrous oxide

exerts little effect on carbon dioxide response but
Inhalational Anesthesia

199

is associated with respiratory depression when combined with other potent agents.50 Elimination of

nitrous oxide is via the pulmonary system, with

minimal biotransformation. The main complications associated with the use of nitrous oxide center

on its association with the diffusion anoxia experienced on anesthetic emergence; its ability to

expand in closed, gas-containing spaces; and

a dose-related bone marrow depression caused

by the inhibition of methionine synthetase, which

is a cofactor in amino acid and vitamin metabolism.

UPTAKE AND DISTRIBUTION

Biophysical Properties

The amount of inhalational anesthetic agent that

is delivered to a patient can be expressed as a

percentage of the total gas volume delivered (vol %)

or as a partial pressure of the total gas pressure (mm

Hg). The convention in the United States is to use

the expression “volume percent delivered,” but an

understanding of partial atmospheric pressure is

essential to appreciate how anesthetic agents reach

equilibrium. For example, a 2% concentration of

isoflurane delivered at sea level at standard temperature with a standard barometric pressure (Pbar)

of 760 mm Hg (ie, 1 atm) would contain a partial

pressure of 15.2 mm Hg (0.02 • 760 = 15.2) isoflurane.

However, if 2% isoflurane were to be delivered at an

elevation of 6,000 ft above sea level (a slightly higher

elevation than that seen in Denver, Colo.), where

the Pbar is 609 mm Hg, the calculated delivered

partial pressure would be 12.2 mm Hg. To further

complicate the issue, if a modern temperature-compensated variable-bypass vaporizer were used, the

vaporizer constants would be (a) the gas dilution

ratio of the vaporizer (21:1 diluent gas to gas flow at

2% flow) and (b) the saturated vapor pressure of

isoflurane (238 mm Hg), both of which are independent of Pbar. The actual delivery of isoflurane set at

2% on the dial at an altitude just higher than that of

Denver, Colorado, would be 17.1 mm Hg (or 2.8%

isoflurane) instead of the calculated 15.2 mm Hg.

Therefore, it may be more prudent to consider anesthetic delivery in terms of partial pressure rather

than volume percent (Figure 9-4).27

Although the inhalational anesthetic agents are

delivered via the pulmonary alveolar bed, and the

desired inhaled and exhaled anesthetic concentrations are measured as alveolar gas concentrations,

the primary intent is to deliver these agents to the

brain. The main determinant of anesthetic delivery

to target tissues is the biophysical property of solubility, which is also related to anesthetic potency.

As the brain is an organ that is extraordinarily well

perfused, the partial pressure of anesthetic agent in

the blood and that of the brain approach equilibrium very quickly. The exchange of anesthetic

gases across the alveolar membrane is quite efficient, and the partial pressure of agent in the pulmonary circulation is very close to that found in the

alveolar gas; therefore, the brain partial pressure

closely follows alveolar partial pressure. The reason that patients do not fall asleep immediately on

exposure to an anesthetic gas, or wake up immediFig. 9-4. The numbers represent gas

flows in milliliters per minute for a

2% isoflurane gas mixture by passing

through a vaporizer with a 21:1 splitting ratio at a constant temperature

of 20°C. Reprinted with permission

from Longnecker DE, Miller FL. Pharmacology of inhalational anesthetics.

In: Rogers MC, Tinker JH, Covino

BG, Longnecker DE. Principles and

Practice of Anesthesiology. St. Louis,

Mo: Mosby–Year Book; 1993: 1057.
Anesthesia and Perioperative Care of the Combat Casualty

200

ately on discontinuation, is mainly due to the solubility of the anesthetic agent in the blood. It may be

helpful to understand that the uptake of anesthetic

agent occurs in three stages of delivery:

1. vaporization and delivery into the airways,

2. transfer across the alveolar membrane with

uptake into the blood, and

3. transfer from the blood across a tissue

membrane, with uptake into target tissue.

There may be factors that influence any of these

stages of anesthetic delivery.

The solubility of an anesthetic agent can be expressed as a partition coefficient, which is essentially the ratio of the solubilities for two media.

Partition coefficients are independent of partial pressure and are critical in describing uptake and distribution properties of each agent. An example would

be the brain–blood partition coefficient, which quantitates the ratio of solubility for blood compared

with that of the brain. The solubility of anesthetic

agents in the blood and tissues determines how

much drug uptake is required across the alveolar

membrane to increase anesthetic partial pressure in

the brain, the ultimate target organ for anesthetic

agents. Drug uptake ultimately influences the time

of induction or emergence from anesthesia. A low

blood–gas partition coefficient is desirable for a

potent anesthetic agent.

Three points need to be appreciated regarding

the practical use of inhalational agents. First, to

reach equilibrium, the direction that gas molecules

move will always be from the higher partial-pressure phase to the lower. Second, when partial

pressures are expressed for media in both gaseous

and nongaseous phases, the ultimate reference is to

the gaseous phase. Third, the actual amount of

vapor contained in a nongaseous phase (eg, within

tissues) depends on the partial pressure and its

solubility in that particular tissue. This is important, as different body tissues such as brain, muscle,

and fat have different partition coefficients, which

are expressed as the brain–blood, muscle–blood,

and fat–blood coefficients. Prior to achieving equilibrium, an inhalational agent moves from alveolar

gas to blood, then to brain, to muscle, and finally to

fat. Well-perfused tissues such as the brain are

called the vessel-rich group, whereas poorly perfused tissues such as fat are called the vessel-poor

group. The brain may reach an anesthetic partial

pressure concentration that is adequate for anesthesia, while the partial pressure lags behind in the

vessel-poor tissues. On termination of inhalational

anesthetic agents, the order is reversed, but ultimate excretion of anesthetic gas is limited to these

pressure gradients (Figure 9-5).

The blood–gas coefficient of nitrous oxide at 37°C

is 0.47 and is one of the lowest of the available

inhalational agents. However, this coefficient is

still approximately 31-fold greater than the blood–

gas coefficient for gaseous nitrogen. When nitrous

Fig. 9-5. A representation of the distribution of partial

pressures (mm Hg) and concentration (vol %) of 2% enflurane

into body tissues 10 minutes after induction of anesthesia.

At this time, alveolar partial pressure is approximately half

of inspired pressure. The anesthetic flow is in the direction

of decreasing partial pressure, and is quantitatively represented by the magnitude and direction of the arrows. Note

that the vessel-rich groups are close to equilibrium with

blood and that the muscle and fat groups are not. The

concentration of enflurane depends on partition coefficients, and anesthetic uptake continues into vessel-rich and

fat groups. If the anesthetic were terminated at this point,

the fat group would continue to take up anesthetic while the

vessel-rich groups would begin to release agent back into

the blood for ultimate elimination through the lungs. Reprinted with permission from Longnecker DE, Miller FL.

Pharmacology of inhalational anesthetics. In: Rogers MC,

Tinker JH, Covino BG, Longnecker DE. Principles and Practice

of Anesthesiology. St. Louis, Mo: Mosby–Year Book; 1993: 1059.
Inhalational Anesthesia

201

oxide is administered, it will exchange for nitrogen

and occupy a volume 30-fold greater than that occupied by nitrogen. At equilibrium using an inhalational gas mixture that contains 70% nitrous oxide,

any gas-filled cavity—whether caused by a pathological or a therapeutic process—will expand in

size up to 4-fold. Therefore, the use of nitrous oxide

is contraindicated in those situations (eg, bowel

obstruction, thoracic injury). Although the same

exchange phenomenon occurs with the potent inhalational agents, their partial pressures are small (eg,

2% isoflurane vs 70% nitrous oxide) and they occupy less volume in gas-filled spaces.

Factors Affecting Uptake and Distribution

When an anesthetic mixture is selected for administration, three variables must be taken into

account for the intended alveolar partial pressure of

the desired agent to be achieved. First, the gas

circuit itself must be washed out with the fresh gas

mixture to achieve a circuit concentration equal to

that selected on the vaporizer. This can be accomplished by elapsed time, high gas flows, and the

overpressure effect (ie, selecting an initial higher

inspired concentration than is ultimately intended).

Second, the inhalational agent will move into rubber and plastic parts of the anesthesia circuit (as

predicted by the rubber–gas partition coefficient)

and the soda lime absorbent will also absorb agent

to some degree. The third and most important

factor is the concept of alveolar gas uptake (FAx) in

relation to the inspired fractional concentration (FI

x)

and the ultimate uptake by the blood (x). This has

been expressed as FAx/FI

x (Figure 9-6). The major

factors that can delay anesthetic uptake to the brain

include

• highly soluble anesthetic agents,

• a state of increased cardiac output, and

• a large gradient between the partial pressures of alveolar and mixed-venous blood.

Increasing the speed of delivery of the inhaled agents

to the brain can be simply accomplished by increasing the inspired partial pressure of the anesthetic or

by increasing alveolar ventilation. Figure 9-7 demonstrates how partition coefficients for various tissue groups affect drug delivery to these sites.

Two other phenomena that can affect anesthetic

uptake are known as the concentration effect and

the second-gas effect. When high concentrations

(ie, overpressures) of gas are delivered, large volumes of gas are removed by alveolar uptake and a

large gradient is established. Returning expired

gases are enriched and concentrated by the high

inspired concentration, therefore maintaining a high

inspired fraction. The second-gas effect is stated,

Fig. 9-6. A comparison of different

agents regarding the increase of alveolar fractional concentration (FAx)

toward that of inspired concentration (FI

x) over time. Agents that are

less soluble in blood rise more rapidly. Reprinted with permission from

Longnecker DE, Miller FL. Pharmacology of inhalational anesthetics. In:

Rogers MC, Tinker JH, Covino BG,

Longnecker DE. Principles and Practice of Anesthesiology. St. Louis, Mo:

Mosby–Year Book; 1993: 1062.

FAx/FI

x

Time (min)
Anesthesia and Perioperative Care of the Combat Casualty

202

Fig. 9-7. A comparison of anesthetic

partial pressures in body compartments for enflurane over time. The

vessel-rich group lags behind alveolar concentration for about the first

10 minutes of administration. The

muscle group lags behind substantially more, and does not reach even

10% of the fresh gas concentration of

enflurane until about 30 minutes after induction. Reprinted with permission from Longnecker DE, Miller FL.

Pharmacology of inhalational anesthetics. In: Rogers MC, Tinker JH,

Covino BG, Longnecker DE. Principles

and Practice of Anesthesiology. St. Louis,

Mo: Mosby–Year Book; 1993: 1063.

essentially, as follows: if one gas is taken up in high

concentrations by the blood, then any other gas

associated with the first gas may be similarly affected. This has implications regarding alveolar

oxygen, which can be increased when high concentrations of nitrous oxide are administered. The

phenomenon may also be seen in reverse, especially

with nitrous oxide, if a diffusion anoxia occurs at

the termination of anesthesia. If nitrous oxide has

been used, hypoxia can be avoided by providing the

patient with oxygen for several minutes at the conclusion of the operation.

Minimal Alveolar Concentration

The understanding of the potency of the inhaled

anesthetic agents during their clinical administration was made conceptually simpler by the introduction of the term MAC in 1965.51 MAC was

defined as the minimal alveolar concentration (in

volume percent of atmosphere) of an anesthetic that

prevented movement in 50% of subjects in response

to a noxious stimulus. Although it was originally

defined in terms of volume percent, the relevant

unit for MAC is actually partial pressure. This unit

is most important when anesthetics are administered under hyperbaric or hypobaric conditions

and has been introduced earlier in this chapter. The

MAC for each agent is not static and may vary with

the age of the patient, extremes of physiology, the

environment (eg, temperature), and the effects of

drugs or alcohol. The addition of drugs such as

narcotics or sedatives lowers inhalational MAC requirements to prevent patients from responding to

the noxious stimulus of a surgical incision. Conceptually, MAC parallels the median effective dose

(ED50) that has been described for other pharmacological agents. Since most clinicians would prefer

that fewer than 50% of patients respond to a surgical stimulus, the term anesthetic depth (AD95) is

used to describe the MAC of an anesthetic agent at

which 95% of patients do not respond. A total dose

of approximately 1.3 MAC prevents movement in

nearly all patients during surgery.52 The MAC and

AD95 for each of the inhalational agents are found in

Table 9-1. In addition, other values such as MACawake (the concentration at which awareness returns) have been described. A very useful and

important concept of MAC is that MACs are additive and may also be proportionally substituted. In

other words, inhalational agents may be added to

one another, and their combined MACs are equal to

that of a single agent. This concept is commonly

used clinically when 70% nitrous oxide (0.66 MAC)

is combined with another potent inhalational agent

such as 0.74% isoflurane (0.64 MAC) in oxygen to

administer a total dose of 1.3 MAC (0.66 MAC + 0.64

MAC = 1.3 MAC).

Time (min)

FAx/FI

x
Inhalational Anesthesia

203

MAJOR ORGAN SYSTEM EFFECTS OF THE POTENT INHALED AGENTS

inspiration. The physiological goal is to maintain

oxygen, carbon dioxide, and hydrogen ion concentration (clinically represented as blood pH) in normal ranges, and the feedback for these parameters

is accomplished by chemoreceptors within the medulla that are in close relationship with the cerebral

spinal fluid. The inspiratory centers are sensitive to

changes in pH and concentrations of carbon dioxide. If the alveolar ventilatory response is plotted

against carbon dioxide concentration and pH, a response curve can then be constructed (Figure 9-8). A

decrease in the PO2 will increase the slope of the curve,

while a state of acidosis will shift the curve to the

left without a change in slope.

The administration of halothane, enflurane, or

isoflurane will cause a dose-dependent decrease in

the ventilatory response to carbon dioxide, with

enflurane tending to be the most potent in this

regard. This is graphically expressed by a decreased slope of the carbon dioxide–response curve

without a shift to either the left or the right. Clinically, in the patient who is spontaneously breathing

a potent inhalational agent at a surgical plane, the

PaCO2 should be in the range of 50 to 55 mm Hg. A

reaction to surgical stimulation may lower this response by 4 to 5 mm Hg. The addition of a narcotic

to a potent inhalational anesthetic technique will

further depress and shift to the right the slope of the

carbon dioxide–response curve.

The Central Nervous System

The clinical endpoint of the potent inhalational

anesthetic agents is a dose-related, reversible depression or excitation of brain function that results

in the anesthetized state. This change in CNS function is associated with alterations in cerebral metabolic rate for oxygen (CMRO2), CBF, EEG changes,

and somatosensory (SSEP) and motor evoked potentials (MEP). In the normal brain, CBF and CMRO2

enjoy a proportionally coupled relation that does

not usually change independently. Under inhalational anesthesia with the potent volatile agents,

there appears to be an uncoupling of the normal

CBF:CMRO2 ratio with increasing anesthetic doses.

It is important to realize that this effect is seen only

when cerebral vascular autoregulation is intact and

normal intracranial blood pressure ranges (50–150

mm Hg) are maintained. An increase in cerebral

vasodilation with increased CBF results in a decrease in CMRO2. This effect is diminished or abolished with decreasing blood pressure. The effect is

Although there is no one perfect anesthetic agent,

an ideal one would have the characteristics listed in

Exhibit 9-1. Until the perfect anesthetic agent can be

produced, the potent inhalational agents—

halothane, enflurane, isoflurane, desflurane, and

sevoflurane—provide the major components needed

in a single, complete anesthetic agent: analgesia,

amnesia, hypnosis, and relaxation of skeletal

muscles. Unfortunately, all the potent inhaled agents

alter normal organ-system physiology. For the sake

of simplicity, only the effects of the first three potent

agents on major organ systems will be discussed,

and those briefly.

The Respiratory System and the Carbon

Dioxide–Response Curve

Control of respiration is mediated by the medulla and the pons. Inspiration and expiration are

modulated within the medulla at the dorsal respiratory group and the ventral respiratory group, respectively. In the pons, the pneumotaxic center

regulates the rate and pattern of respiration and the

apneustic center theoretically has a feedback loop

to the dorsal respiratory group to affect maximal

EXHIBIT 9-1

CHARACTERISTICS OF AN IDEAL

INHALATIONAL ANESTHETIC AGENT

Absence of flammability

Easily vaporized at ambient temperature

Low blood solubility (rapid induction and

recovery from anesthesia)

Minimal metabolism

Compatible with epinephrine

Produces skeletal muscle relaxation

Suppresses excessive sympathetic nervous

system response

Not irritating to airways

Absent or minimal myocardial depression

Absence of cerebrovascular dilation

Absence of hepatic and renal toxicity
Anesthesia and Perioperative Care of the Combat Casualty

204

Fig. 9-8. The effects of increased arterial PCO2 and decreased arterial pH on the rate of alveolar ventilation.

Reprinted with permission from Guyton AC. Textbook of

Medical Physiology. 8th ed. Philadelphia, Pa: WB Saunders;

1991: 447

CMRO2 may be beneficial, especially in the setting

of an isoelectric EEG, halothane has been associated

with dangerously low levels of CMRO2 that may

reflect cerebral toxicity. Enflurane has been associated with seizure activity at 1.5 to 2 MAC concentrations, with a resultant 50% increased CMRO2. On

the other hand, isoflurane can cause an isoelectric

EEG that is associated with a 50% reduction in

CMRO2. The effective recording of SSEPs is not

abolished by concentrations of 0.5 to 0.75 MAC with

any of the volatile agents. Data concerning the

recording of MEPs during inhalational anesthesia

are sparse, although MEPs appear to be hindered at

clinical doses. Recent work concerning the successful recording of spinal evoked potentials (SpEP) in

animals during 1.3 to 2.0 MAC halothane has entered the literature.54

The Cardiovascular System

All of the potent, volatile anesthetic agents depress the cardiovascular system, but their hemodynamic effects differ. The clinical endpoint of cardiovascular depression is hypotension. Halothane’s

effect is due mainly to a decrease in myocardial

contractility and rate, with minimal decrement in

SVR. Enflurane causes both myocardial depression

and decreased SVR, while isoflurane’s effect is

due mainly to its action on SVR. The newer agents

can be expected to have an effect on the cardiovascular system similar to that of isoflurane. This

depressive effect is dose related, and for any potent

volatile anesthetic, the arterial blood pressure can

be decreased by approximately 50% of baseline by

the administration of 2 MAC of agent. Although

halothane is associated with negative chronotropic effects, both enflurane and isoflurane may

cause an increase in heart rate. This chronotropic

effect may be related to halothane’s impairing the

baroreceptor function to a greater degree than

enflurane or isoflurane, but studies with animals55

indicate that while isoflurane may depress both

vagal and sympathetic function, vagal depression

predominates, leading to a noticeably increased

heart rate. This positive chronotropic effect with

isoflurane is seen especially in younger patients

but tapers off after age 40. Cardiac output is decreased—due mainly to a decreased stroke volume—by halothane and enflurane (minimally

by isoflurane). All of the aliphatic hydrocarbon

anesthetic agents sensitize the myocardium to circulating catecholamines; this effect is greatest for

halothane and least for isoflurane. Because of

also blunted by an increase in the amount of

hypocapnia produced. Therefore, the cerebral vasodilation caused by the volatile anesthetic agents

can be attenuated by hypocapnia, although these

responses may not be operative in the injured brain.

Of the three inhalational agents under discussion,

halothane is the most potent cerebral vasodilator,

followed by enflurane and isoflurane. The main

problem associated with increased CBF is that the

cerebral volume is increased, with a resultant increase in ICP. Critical CBF (cCBF) has been defined

as the flow at which ipsilateral EEG changes indicative of cerebral ischemia are seen.53 In the presence

of halothane, the cCBF is 18 to 20 mL/100 g/min; for

enflurane, it is 15 mL/100 g/min; and for isoflurane,

10 mL/100 g/min.

At clinically useful concentrations, halothane

cannot cause an isoelectric EEG. While decreasing
Inhalational Anesthesia

205

its vasodilating effects, isoflurane has been implicated theoretically in the phenomenon of coronary

steal in dogs, but this effect has not been proven

clinically in human subjects.56

The Hepatic System

Because of its high metabolic rate, the liver is

a highly vascular organ; it receives 25% of the cardiac output. The blood supply consists of two

parallel circulations: the hepatic artery supplies

fully oxygenated blood at high pressure, and the

low-pressure portal vein supplies partially

desaturated blood from the splanchnic bed. Owing

to this unique anatomical arrangement, the hepatic

cells adjacent to the hepatic venules are very susceptible to hypoxia, and centrilobular necrosis can

occur. Although autoregulation of total hepatic

blood flow can be demonstrated during the metabolically active fed state in dogs, its presence in

humans is controversial. Hepatic blood flow is

subject to the effects of multiple hormones. The

main determinants of hepatic compromise during

inhalational anesthesia are related to diminished

total hepatic blood flow, which is primarily due to

decreases in cardiac output and mean arterial blood

pressure. Halothane is more closely associated

with these decrements in total hepatic blood flow,

cardiac output, and blood pressure than is

isoflurane, and although the data are limited,

enflurane appears to be similar to halothane.57 Hepatic oxygen supply–demand ratios are better preserved by isoflurane than by halothane.58 Other

factors that may compromise total hepatic blood

flow include (a) an operative site near the liver and

(b) the use of controlled ventilation with high peak

pressures and positive end-expiratory pressures,

which causes an increase in hepatic venous pressure. The metabolism of drugs with a high extraction ratio is affected by decreased total hepatic

blood flow. Finally, transient elevations of liver

function tests sometimes occur following anesthesia, but owing to the enormous reserve of the liver,

the significance of these elevations is not known

and possibly may be related to a surgical site close

to the hepatic bed.

The Renal System

The potent inhalational anesthetic agents usually have an adverse impact on renal function due to

the secondary effects of the altered cardiovascular,

endocrine, and sympathetic nervous systems. The

main determinants of an adverse renal outcome are

decreased cardiac output and blood pressure. These

effects on the renal system are typically transient in

nature and resolve spontaneously once the anesthetic action has been terminated. The main key to

preventing these altered physiological effects is the

maintenance of an adequate preoperative state of

hydration. All the potent inhalational agents in use

today are fluorinated to some degree, and there is

some concern that inorganic fluoride released during their oxidative dehalogenation during hepatic

metabolism can cause a primary renal injury. Renal

injury from this cause is rarely seen clinically. Owing

to the way it is metabolized, enflurane can theoretically place the kidney at the most risk for fluoride

toxicity, although a recent clinical study59 did not

support this contention. Interestingly, the metabolism of sevoflurane, the newest halogenated agent,

is associated with increased serum fluoride levels

and may again open this issue to further discussion

and investigation.

It is impossible to predict the nature of deployments. The most reasonable assumption is that

most military anesthesia in the future will take

place in the DEPMEDS environment of ISO (International Standards Organization) shelters and

TEMPER (tents, extendable, modular, personnel)

tents. However, reasonable alternative possibilities range from the marked austerity of draw-over

devices in shelters of opportunity to the sophistication of servo-mechanism ventilators in modern,

host-nation, fixed facilities. Most anesthesiologists

routinely use a balanced anesthetic technique in

their peacetime practice, and it should be possible

ANESTHESIA IN THE FIELD

to use this same method in the vast majority of field

environments.

Currently, the U.S. Army stocks two devices

for delivering inhaled anesthetic agents, the

Ohmeda Portable Anesthesia Circuit (PAC) and

the Ohmeda Model 885A field anesthesia machine

(both manufactured by Ohmeda, Inc., Madison,

Wis.), in its DEPMEDS inventory. The Ohmeda

PAC is a draw-over device, and the 885A is an

anesthesia machine based on flow-over technology.

Neither apparatus is supplied with a ventilator,

although many field hospitals do carry small ventilators as separate items of operating room equip-
Anesthesia and Perioperative Care of the Combat Casualty

206

ment. Until recently, little or no training

was provided on either apparatus. However, the

teaching protocol for the draw-over device is now

being implemented at selected medical centers,

and a protocol for the 885A is being developed (see

also Chapter 2, Combat Anesthesia Overview, and

Chapter 7, Military Anesthesia Machines). Military

anesthesia providers should at least read about

these two devices before they deploy. The drawover device is simple, but its unfamiliarity may

cause the inexperienced anesthesiologist some concern. The 885A is an actual anesthesia machine and

may appear more familiar than the PAC to the

unpracticed eye, but it, too, has dangers associated

with its operation. The 885A is capable of delivering hypoxic mixtures of nitrous oxide and oxygen,

and the ambient temperature in the operating room

can drastically affect the output of the vaporizer.

These two design problems can lead to lethal hypoxic mixtures.60

Both halothane and isoflurane are available

through the medical logistics system. As a general

rule, if the logistical support necessary for surgery

is available, the support will also be sufficient to

perform the usual anesthetic methods. More than

anything else, the condition of the patient will dictate the anesthetic technique. For example, if routine surgery is being done on children as part of a

civil action program, an inhalational technique

might be selected. On the other hand, some casualties with traumatic injuries will be severely

hypovolemic and will not be able to tolerate any

anesthetic at all until the hemorrhage is controlled

and volume and red blood cell mass restored. A

common practice in these latter cases is to begin the

procedure with oxygen, a muscle relaxant, and scopolamine (as an amnestic agent), and then carefully

titrate small increments of inhaled agents as the

casualty’s vital signs begin to improve. In other

words, anesthetic practice in the field will usually

closely resemble the balanced techniques prevalent

in peacetime practice.

SUMMARY

Inhalational anesthetic agents are the most important drugs in the pharmacopoeia of both military anesthesia providers and civilian practitioners.

It is, therefore, not a little odd that their mechanism

of action remains imperfectly understood. Although

there is clear evidence that anesthetic potency correlates with lipid solubility, the physical basis for

this observation is unknown. It is unlikely to be due

to a generalized expansion of the lipid membrane

that is caused by the presence of a large volume of

the inhalational agent, which thereby prevents normal function of ionic channels. More likely explanations are that inhalational agents either (a) perturb the normal, ordered structure of the bilipid

membrane or (b) reversibly alter lipids in contact

with proteins in ionic channels; both changes interfere with membrane excitability. There is less doubt

about the site of action of inhalational anesthetics:

this is at the neural synapse rather than at the axon.

Presently used inhalational agents fall into two

categories: the alkanes, such as halothane, and the

ethers, such as enflurane and isoflurane. Halothane

is more potent and less irritating to the airway than

more recently developed inhalational agents, has

the propensity to sensitize the myocardium to epinephrine, and may cause severe hepatotoxicity (in

isolated instances). Enflurane, although less potent

than halothane, has fewer of the potential side effects of the latter. Isoflurane is notable for its ease of

administration, lack of serious hepatotoxicity, and

minimal biotransformation with fluoride-ion production. Isoflurane is associated with dose-dependent hypotension that is solely mediated by a decrease in systemic vascular resistance and not by

myocardial depression.

The amount of inhalational anesthetic agent that

is delivered to a patient can be expressed as a

percentage of the total gas volume delivered or as a

partial pressure of the total gas pressure. The solubility of an anesthetic agent can be expressed as a

partition coefficient, which is essentially the ratio of

the solubilities for two media. The solubility of

anesthetic agents in the blood and tissues determines how much drug uptake is required across the

alveolar membrane to increase the partial pressure

of the anesthetic agent in the brain, the ultimate

target organ for anesthetic agents. Major factors

can delay anesthetic uptake to the brain, including

the use of an agent with a high solubility, a state of

increased cardiac output, and a large gradient between the partial pressures of alveolar and mixedvenous blood. The amount of inhalational agent

required is quantitated as the MAC, and is measured as the partial pressure.

Inhalational agents have the potential to cause

major organ dysfunction outside the CNS. Depres-
Inhalational Anesthesia

207

sion of the respiratory and cardiovascular systems

is to be expected. The liver and kidneys are at risk

from decreased blood flow and, in rare instances,

devastating agent-induced toxicity.

The administration of inhalational agents in deployed hospitals requires a special understanding

of the characteristics of the agents because they will

be administered by draw-over and flow-over technologies. Halothane and isoflurane are available in

DEPMEDS-equipped hospitals.

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Chapter 10

INTRAVENOUS ANESTHESIA

DONALD J. FOX, M.D.*; LISA D. SAUNDERS, M.D.†; EMIL J. MENK, M.D.‡; AND ROBERT MIDDAUGH, M.D.§

INTRODUCTION

INTRAVENOUS ANESTHETIC AGENTS FOR BATTLEFIELD ANESTHESIA

USEFUL DRUGS FOR THE INDUCTION OF ANESTHESIA

Barbiturates

Etomidate

Propofol

Ketamine

ANXIOLYTIC AND AMNESTIC AGENTS

Benzodiazepines

Scopolamine

Droperidol

ANESTHETIC AGENTS THAT PRODUCE ANALGESIA

Opioid Agonist Drugs

Opioid Agonist–Antagonist Drugs

Opioid Antagonist Drugs

TECHNIQUES FOR USING INTRAVENOUS ANESTHETICS

Rapid-Sequence Intravenous Induction

Adjuvants to Inhalational Anesthesia

Total Intravenous Anesthesia

Adjuvants for Regional and Local Anesthesia

SUMMARY

*Formerly, Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Department of Surgery, Brooke Army Medical Center, Fort

Sam Houston, Texas 78234-6200; currently, Chief, Department of Anesthesia, Mercy Medical Center, 1512 12th Avenue Road, Nampa, Idaho

83686

†Formerly, Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Department of Surgery, Letterman Army Medical Center,

Presidio of San Francisco, California 94129-6700; currently, Staff Anesthesiologist, Stanford Medical Center, 300 Pasteur Drive, Stanford,

California 94305

‡Formerly, Lieutenant Colonel, Medical Corps, U.S. Army; Chief, Anesthesia and Operative Service, Department of Surgery, Brooke Army

Medical Center, Fort Sam Houston, Texas 78234-6200; currently, Staff Anesthesiologist, Presbyterian Hospital, 200 Hawthorne Lane,

Charlotte, North Carolina 28204

§Formerly, Major, Medical Corps, U.S. Army Reserve; Anesthesia and Operative Service, Department of Surgery, Brooke Army Medical Center,

Fort Sam Houston, Texas 78234-6200; currently, Staff Anesthesiologist, St. Vincent Infirmary Medical Center, 2 St. Vincent Circle, Little

Rock, Arkansas 72205
Anesthesia and Perioperative Care of the Combat Casualty

212

INTRODUCTION

Delivering safe and effective anesthesia to casualties with combat injuries presents unique challenges to military trauma anesthesiologists. These

casualties may have sustained severe injuries involving significant blood loss and varying degrees

of shock. They will be in pain and emotional distress, and possibly suffering from sequelae of prolonged transport such as inadequate ventilation,

hypothermia, uncorrected hypovolemia, in any combination. They may have full stomachs, which

places them at risk for pulmonary aspiration during

general anesthesia.

Certain other conditions in the field further complicate the anesthetic management of these difficult

patients. For one, casualties may arrive en masse,

exceeding the ability of a small medical staff to

provide scrupulous individual monitoring. In these

situations, relatively untrained personnel may be

required to achieve airway patency and hemodynamic stabilization in the perioperative period.

Likewise, recovery care after anesthesia may be marginal. As for the course of the anesthetic itself, bulky

and elaborate anesthesia equipment may not be available or practical at the site of combat casualty surgery.

In particular, apparatus for the delivery of compressed

gases such as oxygen may pose logistical problems.

Ideally, then, an anesthetic approach for combat

casualty care should have the following characteristics: preservation of airway reflexes with minimal

hemodynamic effects; ease of delivery, which would

allow for management by relatively unskilled practitioners; and a minimal requirement for unwieldy

or complex anesthetic delivery systems. Unfortunately, no anesthetic technique meets all of these

requirements, although many approaches have been

used with varying degrees of success in the battlefield setting. Among these are general anesthesia

using simple gas-delivery systems, regional techniques, and intravenous anesthesia with or without

supplementary inhaled agents. A full discussion of

the first two methods is presented in Chapter 8,

Closed-Circuit Anesthesia; Chapter 9, Inhalational

Anesthesia; and Chapter 12, Regional Anesthesia.

In general, their use dictates a significant level of

skill on the part of the practitioner, particularly in

dealing with hypotension, which is a sequela of

both regional and general anesthesia, and from the

loss of airway reflexes that ensue from general

anesthesia with volatile agents.

Intravenous anesthetic agents are advantageous

in the field for many reasons. Transportability and

technical ease of administration are excellent. Many

of these drugs are able to rapidly induce a state of

surgical anesthesia. This is particularly important

in traumatized soldiers, as experience has shown

most to have full stomachs at the time of injury.1

 To

prevent the aspiration of regurgitated material into

the lungs, a rapidly induced state of unconsciousness is necessary to facilitate endotracheal intubation

and airway protection. With careful use, these drugs

will also allow early awakening and extubation of the

trachea, shortening stays in the recovery area. Residual analgesia is a benefit with some intravenous

agents. These drugs can also be used to supplement

inhalational anesthetic agents, providing balanced

anesthesia. Some intravenous anesthetic agents can

be used as the sole or primary agents for the maintenance of surgical anesthesia by means of an initial

bolus followed by continuous infusion. This technique adds a degree of controllability to the duration of action of the anesthetic and reduces the total

amount of drug administered, allowing the anesthesia provider to have an awake patient at the end

of the case. Such a patient will be easier for recovery

area personnel to deal with than an overly sedated

or unconscious patient. Indeed, recovery room

personnel may be in very short supply or extremely

busy. As the patient may receive relatively little

attention during this period, recovery time is best

kept to a minimum.2

INTRAVENOUS ANESTHETIC AGENTS FOR BATTLEFIELD ANESTHESIA

the intravenous drugs we will discuss in this chapter each provide one or more component parts of

the ideal (ie, complete) anesthetic regimen.

Much of the initial anesthetic care of combat

casualties consists of the vigorous resuscitation of

hemorrhagic shock. It is likely that many of these

injured soldiers would not survive the physiological effects of the sudden imposition of a complete

Complete surgical anesthesia, when properly

administered, provides amnesia, analgesia, unconsciousness, and muscle relaxation. The ideal anesthetic drug would induce such a state of surgical

anesthesia rapidly, be quickly reversible, maintain

hemodynamic stability, and be nontoxic to the patient. There is no drug available today that, when

used alone, satisfies all of these criteria. However,
Intravenous Anesthesia

213

anesthetic, which could compound the hemodynamic instability seen with hypovolemic shock

states. Careful selection and meticulous titration of

anesthetic agents, whether inhalational or intravenous, usually become feasible only as resuscitative

efforts progress. Failure to recognize and adequately

treat hypovolemic shock before the induction of

anesthesia can convert a casualty to a fatality. Indeed, the careless use of thiopental in hypovolemic

patients after the Japanese attack at Pearl Harbor on

7 December 1941 caused a large number of intraoperative deaths and led some anesthesiologists to

criticize its use in war casualties.3 It is clear in

retrospect that many of the anesthesia providers

involved were unfamiliar with the proper use of

this agent. It is also clear that volume resuscitation

was inadequate in these cases. Thiopental was

subsequently used with good success throughout

the remainder of World War II,4–8 the Korean and

Vietnam wars,1 the Falklands War,9 and remains a

valuable anesthetic drug today when properly administered. The intravenous anesthetic and adjuvant drugs currently available have a broad spectrum of effects, indications, and contraindications

(Table 10-1). Each of the agents described in this

chapter has unique advantages and disadvantages

for the anesthetic management of wartime casualties. The anesthesia provider must be able to assess

the clinical situation in each case and select the best

anesthetic technique and agents for the casualty.

For some short surgical procedures, one or two

intravenous bolus injections of anesthetic agent may

be all that is required for patient comfort. For very

minor procedures, a subanesthetic dose may be

sufficient for analgesia, sedation, and anxiolysis.

Subanesthetic doses are also useful for supplementing regional anesthetic techniques. Disadvantages

of many of the intravenous anesthetic agents include the possibility of overdosage, with resultant

respiratory depression or arrest. Mechanical ventilators may not be available at battlefield hospitals.2

Because the patient’s metabolism of the drug is required for these drugs’ termination of action, anesthesia-recovery personnel may be forced to commit themselves to one-on-one care for such patients until they

are once again breathing on their own. Intravenous

TABLE 10-1

PHARMACOLOGICAL EFFECTS OF VARIOUS INTRAVENOUS ANESTHETIC AGENTS

Loss of

Agent Onset Duration Consciousness Analgesia Amnesia

Barbiturates

Thiopental Rapid Ultra-short Yes Anti* Yes

Methohexital Rapid Ultra-short Yes Anti Yes

Benzodiazepines

Diazepam Slow Long High-dose None Yes

Midazolam Intermediate Intermediate High-dose None Yes

Narcotics

Morphine Slow Long High-dose Yes +/–†

Meperidine Slow Long High-dose Yes +/–

Fentanyl Intermediate Intermediate High-dose Yes +/–

Sufentanil Intermediate Intermediate High-dose Yes +/–

Alfentanil Rapid Short Yes Yes +/–

Ketamine Rapid Short Yes Yes Yes

Etomidate Rapid Short Yes No Yes

Propofol Rapid Ultra-short Yes No Yes

Scopolamine Rapid Long No No Yes

*Pain perception is increased

†The effect may or may not be present
Anesthesia and Perioperative Care of the Combat Casualty

214

anesthetic techniques, while technically simple, tend

to be less forgiving of error than inhalational techniques. Constant vigilance and attention to detail

are mandatory when these drugs are used.

Military medical planners have noted that the

limiting factor in performing surgery in the field

may be the number of personnel who are trained to

administer anesthesia.2 It is recognized that many

military physicians and nurses who have had minimal exposure to anesthesiology as a specialty will

have to be trained on the job to deliver a safe

anesthetic. Simplicity, technical ease of administration, and the relatively high margins of safety of

many of the intravenous anesthetic drugs will permit such personnel to deliver safe anesthesia to

combat casualties.

USEFUL DRUGS FOR THE INDUCTION OF ANESTHESIA

recovery from methohexital is slightly faster than

from thiopental.

The brief clinical effect seen after intravenous

bolus of these drugs is not due to metabolism, but

rather to redistribution of agent from the brain and

other vessel-rich organs to less metabolically active

compartments. However, multiple doses or continuous infusions may result in slow recovery, owing to protein binding and the slow release of drug

from muscle and fatty tissues.10

Physiological Effects

Central Nervous System. The barbiturate anesthetic agents induce a state of hypnosis and amnesia. However, they tend to reduce the patient’s pain

threshold (ie, the antalgesic effect), with a resultant

significant increase in heart rate and blood pressure

during painful or stimulating procedures.11

Cerebral metabolic rate is markedly reduced following a dose of a barbiturate drug, which, in turn,

causes cerebral vasoconstriction. This effect, in

turn, results in decreased cerebral blood volume

and reduced intracranial pressure. Cerebral perfusion may improve, as intracranial pressure falls to a

greater extent than the mean arterial pressure in

normovolemic patients.11 These effects are very

beneficial in the patient with a closed head injury.

In addition, the barbiturates are potent anticonvulsant agents.

Cardiovascular System. The principal hemodynamic effects of the barbiturates are a decrease in

contractility and an associated increase in heart

rate. Dose-dependent decreases in arterial blood

pressure, stroke volume, and cardiac output are

seen. The mechanisms for the decrease in cardiac

output include (1) direct negative inotropic effect

on the myocardium, (2) decreased ventricular filling owing to increased venous capacitance, and (3)

transiently decreased sympathetic outflow from the

central nervous system.11

Respiratory System. The barbiturates are potent

central nervous system depressants. As a conseWhen induction of general anesthesia is necessary in casualties with traumatic injuries, two properties of an anesthetic drug are of primary importance. The first is whether the selected drug can be

expected to cause serious depression of the patient’s

cardiovascular system. The patient may be severely

hypovolemic from blood loss, exposure, or other

causes. The choice of an induction agent must

therefore take into account the victim’s volume

status and degree of hemodynamic compromise.

The second important factor in the choice of an

induction agent is the rapidity of onset of unconsciousness following intravenous injection. Because

soldiers injured on the battlefield nearly always

present for treatment with a full stomach,1

 the airway must be rapidly protected with an endotracheal tube to prevent aspiration of gastric contents

into the bronchopulmonary tree. A drug with a

long onset time will therefore expose the patient to

greater anesthetic risk.

Agents that are useful for induction of anesthesia

are presented below, grouped by drug type.

Barbiturates

Intravenous barbiturates produce central nervous system depression ranging from mild sedation to coma, depending on the dosage given. The

two barbiturates most commonly used to induce

anesthesia are sodium thiopental (Pentothal, manufactured by Abbott Laboratories, North Chicago,

Ill.) and methohexital (Brevital, manufactured by

Eli Lilly and Co., Indianapolis, Ind.). These agents

rapidly produce a state of unconsciousness and

amnesia without significant analgesia.

Pharmacology

Thiopental is usually prepared as a 2.5% mixture

(25 mg/mL), while methohexital is made up as a 1%

solution (10 mg/mL). Unconsciousness occurs

within seconds following intravenous bolus and

lasts for approximately 3 to 5 minutes. Clinical
Intravenous Anesthesia

215

quence of these effects, they produce profound respiratory depression. This is first seen as a decrease

in tidal volume, followed by apnea. Positive-pressure ventilation will be necessary following the

usual induction doses of both thiopental and

methohexital.

Clinical Use and Contraindications

Both sodium thiopental and methohexital are

safe induction agents in the normovolemic casualty

whose cardiac function is not compromised. Usual

induction doses are 4 mg/mL for thiopental or 1

mg/mL for methohexital (Table 10-2). Although

these agents are not the drugs of first choice in

trauma patients, experience has shown that they

may also be used safely in such cases, provided that

the dosages are adjusted downward.4–6 Easy

intubating conditions are generally obtained within

60 seconds when given with succinylcholine for

rapid-sequence induction (which is discussed later

in this chapter). Thiopental (or methohexital) may

also be administered as a continuous infusion following an initial bolus (Table 10-3). This allows a

state of surgical anesthesia to be maintained for

extended periods. However, these agents accumulate in the tissues when used in this manner, and

recovery from anesthesia may be prolonged.

Extreme caution should be used in the hypovolemic casualty or one with cardiac compromise

such as tamponade. In general, barbiturates should

be avoided as induction agents in these casualties

until the hypovolemic state or the cardiac tamponade

is corrected.

TABLE 10-3

DRUG DOSES FOR CONTINUOUS INTRAVENOUS INFUSION TECHNIQUES

Agent Loading Dose Infusion Rate

Ketamine 1.0–2.0 mg/kg 20–50 μg/kg/min

Etomidate 0.2–0.4 mg/kg 40–100 μg/kg/min

for 10 min, then

10–40 μg/kg/min

Thiopental 2.0–4.0 mg/kg 0.1 mg/kg/min

Propofol 2.0–2.5 mg/kg 0.1–0.2 mg/kg/min

Alfentanil 100–200 μg/kg* 0.5–2.5 μg/kg/min

TABLE 10-2

SUGGESTED DOSE RANGES FOR INTRAVENOUS INDUCTION OF ANESTHESIA

Casualty’s Resuscitation Status

Normovolemic Hypovolemic

Agent (Dose) (Dose)

Sodium Thiopental

Ketamine

Etomidate

Methohexital*

Midazolam*

Alfentanil 100–200 μg/kg not known

 0.2–0.4 mg/kg

 1–2 mg/kg

0.5–1.0 mg/kg

0.15–0.3 mg/kg 0.075–0.15 mg/kg

*Will cause prolonged sedation and respiratory depression

*30–40 μg/kg when combined with thiopental

0.25 mg/kg

0.1–0.2 mg/kg

 0.5–1.0 mg/kg

2–4 mg/kg 1–2 mg/kg

Etomidate

Etomidate (Amidate, manufactured by Abbott

Laboratories, North Chicago, Ill.) is an imidazole compound that is chemically unrelated to any other intravenous anesthetic agent. It is a potent sedative and

hypnotic agent with rapid onset and recovery, and its

use is associated with excellent cardiovascular and

respiratory stability in the normovolemic patient.12

Pharmacology

As with the barbiturates, etomidate is rapidly

distributed to the brain and other vessel-rich groups

following intravenous injection. Termination of

clinical action occurs as the agent is redistributed

away from these highly perfused organs. 13

Etomidate’s distribution half-life is in the 2- to 4-

minute range. The drug is cleared from plasma 5-

fold faster than is thiopental. Etomidate is prepared

as a 2% solution (20 mg/mL).

Physiological Effects

Central Nervous System. Intravenous injection

causes a rapid, dose-dependent depression of the

central nervous system. As with the barbiturates,

etomidate is a potent anticonvulsant agent. This

anticonvulsant effect lasts significantly longer than

its hypnotic and anesthetic effects. In common with

the barbiturates, etomidate also causes a significant

reduction in the cerebral metabolic rate, with associated cerebral vasoconstriction14 and decreased intracranial pressure. Cerebral perfusion pressure is

not altered appreciably.
Anesthesia and Perioperative Care of the Combat Casualty

216

Cardiovascular System. In normovolemic patients, etomidate causes no significant changes in

heart rate or cardiac output.12 A slight fall in systemic blood pressure may be noted, secondary to a

mild decrease in peripheral vascular resistance.

However, in the trauma patient suffering from hypovolemic shock, serious hypotension may result from

usual induction doses of etomidate due to suppression of sympathetic nervous system outflow.

Respiratory System. Etomidate is a potent central nervous system depressant. As a consequence

of these effects, it produces dose-related respiratory depression. Respiratory rate and tidal volume

are affected, although the magnitude is less than

that produced by the barbiturate anesthetic agents.11

Positive-pressure ventilation will be necessary either after an induction dose or during continuous

infusions for maintenance of general anesthesia.

Clinical Use and Contraindications

The usual dose range for induction is 0.2 to 0.4

mg/kg (see Table 10-2). The clinical duration of a

single bolus injection is 3 to 12 minutes.

Psychomotor recovery is intermediate between

that of thiopental and methohexital. Short surgical

procedures may be done using etomidate, maintaining anesthesia with repeated, small boluses or

continuous infusion (see Table 10-3). Following a

bolus injection of 0.2 to 0.4 mg/kg, a continuous

infusion can be set up to flow at a rate of 40 to 100

μg/kg/min (20–40 μg/kg/min if nitrous oxide is

being used, although nitrous oxide is not available

in deployable hospitals). After the initial 10 minutes of infusion, the rate should be reduced to 10 to

40 μg/kg/min. (Many anesthesiologists would

supplement this infusion technique with a potent

opioid such as fentanyl, since etomidate is an incomplete anesthetic, ie, it provides no analgesia).

Prudence would dictate a reduction in drug dose

for induction of anesthesia during the resuscitative

phase of shock (ie, in the acutely traumatized battlefield casualty). A good starting dose would be 0.1

mg/kg, titrating more agent as the patient’s condition allows.

Two characteristics of etomidate make it useful

for anesthesia in the traumatized patient11:

• Relative hemodynamic stability; this is most

important when the casualty is hypovolemic

(eg, in hemorrhagic shock).

• Its effect on the central nervous system; by

decreasing intracranial pressure and cerebral metabolic rate while preserving stable

hemodynamic parameters, etomidate may

prove to be the agent of choice for anesthetic induction in the hemodynamically

unstable trauma patient with a head injury.

Relatively minor drawbacks to the use of

etomidate include the following11:

• Venous irritation; etomidate is dissolved in

propylene glycol, giving rise to pain or

irritation or both on intravenous injection

in some patients. This side effect can be

reduced somewhat by prior administration

of an opioid drug such as fentanyl.

• Myoclonus; this centrally mediated effect

is frequently observed. It is not indicative

of awareness, and is not harmful to the

patient, per se. Once again, these movements may be reduced by pretreating the

patient with an opioid drug.

• Postanesthetic nausea and vomiting; this

side effect may be seen in up to 40% of

patients on emergence from anesthesia with

etomidate, is probably centrally mediated,

and may be reduced in incidence if an

antiemetic drug such as droperidol is given.

• Adrenocortical suppression; this effect lasts

from 6 to 8 hours and is probably not clinically significant unless prolonged or large

total doses are administered. Suppression

of adrenal steroid production may predispose critically ill patients to sepsis.

Propofol

Pharmacology

Propofol (Diprivan, manufactured by Stuart Pharmaceuticals, Wilmington, Del.) is a recently introduced intravenous anesthetic agent. It rapidly produces unconsciousness following bolus injection,

with a time course on onset and recovery very

similar to that of thiopental and methohexital.

Propofol is completely insoluble in aqueous solution and is therefore administered in a lecithinbased emulsion. Because this emulsion is a very

favorable medium for bacteria, strict aseptic technique should accompany its use. The drug is extremely lipid soluble, a property that allows it to

cross the blood–brain barrier very quickly. Clinical

experience has shown that less residual postoperative sedation and psychomotor impairment follow

administration of propofol, and side effects such as

nausea and vomiting are uncommon.15
Intravenous Anesthesia

217

Physiological Effects

As do the barbiturates, propofol causes dosedependent cardiac and respiratory depression.11,12,15

The magnitude of these effects is similar to those

seen with thiopental. Propofol has no analgesic

properties but, in contrast to thiopental, neither

does it appear to have an antalgesic effect.

Clinical Usage and Contraindications

Induction of anesthesia is achieved with a

propofol dose of 1.5 to 3.0 mg/kg (see Table 10-2).

Unconsciousness occurs less than 1 minute following an intravenous bolus, and lasts from 4 to 8

minutes. The drug is redistributed and eliminated

very rapidly. A continuous infusion or repeated,

small-bolus injections may be used to maintain a

surgical plane of anesthesia. The drug does not

accumulate in the tissues to a clinically significant

degree and thus is better suited to continuousinfusion techniques than the barbiturates or

etomidate. Recovery is characterized by rapid emergence from anesthesia and minimal postoperative

confusion.15 A continuous infusion may be used

following an induction dose of 2.0 mg/kg (see

Table 10-3). The infusion rate is titrated to the

desired effect, with a usual dose range of 0.1 to

0.2 mg/kg/min (6.0–12.0 mg/kg/h); in critically

ill or debilitated patients, the dosage regimen

may be halved. This technique is enhanced by

the addition of an opioid drug or nitrous oxide

for analgesia.

Propofol’s greatest advantage over other intravenous anesthetic agents is its relatively rapid elimination from the body. This may diminish the degree of hangover seen after continuous infusions or

repeated boluses of the barbiturates and etomidate,

and could potentially shorten time spent in the

recovery area.16

Ketamine

Pharmacology

In the field, the aim of the military anesthesia

provider is to deliver the minimum level of anesthesia necessary to provide adequate surgical depth,

thereby assuring a rapidly resolving anesthetic state.

Ketamine was developed through investigation of

phencyclidine (PCP) and cyclohexamine, both of

which provide profound anesthesia accompanied

by intolerable psychotomimetic effects.17 Ketamine

resembles these drugs structurally, but it delivers

sedation, analgesia, and surgical anesthesia with

much milder psychic side effects.

The administration of ketamine produces an unusual clinical state called dissociative anesthesia (ie,

the patient does not move specifically in response to

noxious stimuli18). Some researchers19 have postulated that ketamine depresses central nervous system centers that are crucial to the transmission of

the emotional component of pain signals from the

spinal cord to the higher centers. Others20,21 believe

that ketamine may work through direct suppression of spinal cord activity or by an action on opiate

receptors throughout the central nervous system.

Ketamine has a rapid onset of action attributable

to its high lipid solubility, and a short duration of

action owing to redistribution out of the central

nervous system. These features make it very similar to the barbiturate induction agents such as sodium thiopental. When ketamine is administered

intravenously, peak plasma levels are achieved in 1

minute, while peak plasma levels following an intramuscular dose are reached by 15 minutes after

the injection. Anesthetic effects last approximately

10 to 15 minutes, and analgesia may last as long as

4 hours. The elimination half-life of ketamine from

the peripheral tissues is 2 to 3 hours. Therefore,

despite the swift termination of its hypnotic effects

after an initial injection, prolonged sedation may

ensue from repeated doses or infusions. The development of tolerance to ketamine may occur following repeated exposures.

Does ketamine meet the requirements for combat

casualty anesthesia? Certainly, it is an extremely

useful agent in this setting. Among its many valuable attributes, ketamine

• is nonlabile in solution and easily transported in powdered form, and can be delivered intravenously or intramuscularly;

• provides a rapid, smooth induction to surgical depth anesthesia, as well as an acceptably brief interval to termination of its sedative effects;

• is a profound analgesic, unlike other nonnarcotic intravenous anesthetic agents; and

• allows the patient’s stable cardiovascular

and respiratory physiology to be maintained, with consequent preservation of

blood pressure and airway reflexes.

This last point is probably the most significant.

However, this is not meant to imply that a patient

under ketamine anesthesia can be left unattended,

since apnea, airway obstruction, aspiration of gas-
Anesthesia and Perioperative Care of the Combat Casualty

218

tric contents, and hypotension may still be seen.

Rather, the use of ketamine allows the administration

of general anesthesia by relatively unskilled personnel with an increased margin of safety when compared to other, more conventional methods. While

not an ideal situation, this may be unavoidable in

times of war. On the negative side, ketamine anesthesia has two major drawbacks in the battlefield setting:

• Time to full recovery is prolonged when

the drug is used as a maintenance agent,

compared with the inhaled anesthetics and

many other intravenous drugs.

• The psychic phenomena accompanying

emergence may be severe in young soldiers.

Nonetheless, it is clear that ketamine’s unique characteristics make it an important tool for use in

combat surgery.

Physiological Effects

Central Nervous System. Ketamine has potent

analgesic actions. However, because of its unique

nervous system effects, the administration of

ketamine produces an anesthetic state unlike that of

more traditional agents such as thiopental or the

opioid narcotics. Thus, it can be difficult to assess

anesthetic depth. When surgical anesthesia is

achieved with ketamine, the patient’s eyes may

remain open and exhibit nystagmus as well as intact

corneal and light reflexes. Myoclonus is observed

frequently, as are actual purposeful movements

that are not necessarily in response to painful stimuli.

Even with very small doses of ketamine, patients

may lose a sense of contact with their environment

and an ability to think coherently. Nonetheless,

with appropriate dosing, a trancelike state accompanied by profound anesthesia can be achieved,

which allows surgery to proceed. A good approach

to assessing the adequacy of anesthesia under

ketamine is to aim for suppression of reaction to

surgical stimulation.22 In other words, the goal

should not necessarily be a completely motionless

patient but rather the dissociative state.18

An unfortunate aspect of ketamine’s central nervous system effects is a phenomenon known as the

emergence reaction. This refers to an altered mental

state experienced by many patients on awakening

from the drug, and is characterized by vivid dreams,

floating or “out-of-body” sensations, disorientation, and hallucinations. Although these feelings

usually end on full awakening, some patients may

experience flashbacklike sensations as late as several weeks after receiving ketamine.17 Frequently

they are very disturbing to the patient. The incidence

of emergence reactions is on the order of 5% to 30%.17,23

Predisposing factors include age older than 16 years,

female gender, a history of emotional problems,

and a history of an active dream life. This phenomenon also occurs more commonly when ketamine is

given rapidly, in relatively large intravenous doses,

and when atropine or droperidol are given as

premedicants. Finally, many anesthesiologists believe that psychic disturbances are exacerbated by a

noisy or otherwise stimulating environment.

The most effective prophylaxis against emergence reactions appears to be the concomitant use

of a benzodiazepine drug.24,25 These drugs are useful either as premedicants or when administered

during the course of an operation. When ketamine

is used solely as an induction agent, followed by

maintenance of anesthesia with other drugs, emergence reactions are virtually unheard of in cases

lasting longer than 45 minutes.23 Some investigators17 suggest preoperative and postoperative counseling regarding possible psychic phenomena as a

very effective means for reducing their incidence.

Cardiovascular System. Ketamine causes doserelated increases in arterial blood pressure and heart

rate. These effects are believed to derive from direct

sympathetic stimulation. Heart rate, blood pressure, and cardiac output are increased, with variable effects on stroke volume and systemic vascular

resistance. These effects make ketamine a very

valuable drug for the induction of anesthesia in patients who are suffering from hypovolemic shock.17

In addition to sympathetically mediated cardiac

stimulation and vasoconstriction, ketamine has been

shown to dilate vascular smooth muscle and to

depress myocardial function by direct actions.26 If

the sympathetic nervous system is depressed by

anesthetic or other drugs, or if the patient is critically ill, a bolus injection of ketamine may cause

profound cardiovascular collapse. Ketamine-induced direct myocardial depression and peripheral

vasodilation are usually effectively masked by its

sympathomimetic actions. In the absence of a fully

functioning autonomic nervous system, the predominant cardiovascular effect of ketamine is to

depress cardiac function.11 At least one authority26

has observed decreases in cardiac performance following the use of ketamine in the setting of acute

trauma, but most investigations of the cardiostimulatory effects of ketamine in the presence of hemorrhagic shock have shown a significant increase in

both systolic and diastolic blood pressure.26–28 Cardiovascular stimulation may be attenuated by in-
Intravenous Anesthesia

219

haled anesthetic agents, sodium thiopental, or

premedication with a benzodiazepine.17,29

Respiratory System. In contrast to the narcotics

and barbiturates, ketamine preserves the respiratory response to carbon dioxide.17 Decreases in the

partial pressures of oxygen in arterial blood (PaO2)

are modest and transient at commonly used doses.

Significant respiratory depression occurs when

ketamine is given rapidly in high doses.

Ketamine is known to produce bronchial smoothmuscle relaxation, which increases pulmonary compliance in patients with bronchoconstriction.17

Tracheopharyngeal reflexes are maintained to a

greater extent than with other commonly used induction agents, but pulmonary aspiration of gastric

contents may occur at even relatively low doses.

Finally, salivation is markedly increased on administration of the drug.30,31

Relative to other intravenous agents, the effects

of ketamine on the respiratory system increase its

margin of safety in the field setting. It maintains

respiratory drive in the spontaneously ventilating

patient, minimizes airway reactivity, and preserves

airway-protective reflexes, at least in part. However, this in no way obviates the need for skilled

airway management, as respiratory depression or

tracheal soiling or both are still possible, particularly when the casualty is not only acutely traumatized but also in a chaotic setting.

Contraindications

Based on the physiological effects just presented,

several clinical conditions constitute contraindications to the use of ketamine. As mentioned, since

postanesthetic emergence reactions are a troublesome side effect, ketamine probably should not be

used when there is preexisting psychopathology.

Ketamine raises intracranial pressure by increasing cerebral blood flow and systemic blood pressure.11 Likewise, intraocular pressure is increased.

Ketamine is therefore contraindicated in casualties

who have closed head or penetrating eye injuries,

and in all other situations where intracranial or

intraocular pressure is raised.

Clinical Use

Ketamine is available in a variety of strengths,

most commonly 10 mg/mL, 50 mg/mL, and 100

mg/mL. The usual intravenous induction dose is 1

to 2 mg/kg. (The intramuscular dose for induction

of anesthesia is 5–10 mg/kg). Following an intravenous induction dose, ketamine is rapidly distributed to the brain and other vessel-rich groups in a

manner analogous to that of thiopental. For short

surgical cases, repeated boluses of one half the

induction dose may be administered at appropriate

intervals as needed. As an alternative to this technique, a solution of 0.1% ketamine may be prepared

(1 mg/mL) and a continuous infusion maintained

at a rate of 25 to 50 μg/kg/min.

Termination of ketamine’s action is due to redistribution (the distribution half-life is 7–11 min) and

hepatic metabolism. The elimination half-life is 2 to

3 hours. Effective analgesia is possible with

subanesthetic bolus doses of ketamine (0.25 to 0.5

mg/kg).

Initial enthusiasm for ketamine as a possible

single-agent, total, intravenous anesthetic has waned

somewhat as actual field trials have demonstrated

its inadequacies. For example, experiences with

ketamine in the Falkland Islands and Southeast

Asia have yielded mixed results. In Cambodia,

British anesthetists have used ketamine as a sole

agent for superficial procedures and brief minor

surgeries, but they reported prolonged recovery

times, particularly when benzodiazepines were used

as a prophylaxis against emergence reactions. In

addition, they noted rare laryngospasm and other

airway compromise.32 During the Falklands War,

total intravenous anesthesia was employed with

success in operations of short duration not involving the body cavity. For more major surgeries in

patients in hypovolemic shock, ketamine was recommended as an induction agent and adjunct to

maintenance with halothane. In the cases described

using this technique, recovery time was not appreciably prolonged despite the routine administration of diazepam at the end of the procedures.

Emergence phenomena were not an issue.33 The

consensus drawn from these two experiences is that

ketamine delivers adequate anesthesia only for peripheral procedures and when used with a benzodiazepine to prevent postoperative delirium.

In the large majority of cases, airway reflexes

were preserved. While supplemental inhaled agents

were deemed necessary for casualties who required

intraabdominal surgery, total intravenous anesthesia was used successfully for over one half of the

casualties who presented to this group of anesthesia providers, owing to the superficial nature of the

surgeries involved. Therefore, with a few provisos,

it would appear that ketamine as a sole agent is a

feasible anesthetic for many situations encountered

in wartime.

A marked improvement in outcome was achieved

through the introduction of an infusion technique,
Anesthesia and Perioperative Care of the Combat Casualty

220

which reduces the total administered ketamine dose.

Two large series25,34 describing both minor and major abdominal procedures under continuous

ketamine infusion report minimal prolongation of

recovery time, with favorable respiratory and cardiovascular effects. Nitrous oxide and muscle relaxants were used, as was diazepam. Very encouraging work has been done by anesthetists in South

Africa who have used a ketamine infusion with

only muscle relaxation and oxygen-enriched room

air for major abdominal cases.35 A critical feature of

their work was the use of a benzodiazepine as the

induction agent, which served to prevent emergence phenomena but also prolonged the recovery

phase. The clear advantage of such a technique

to field anesthesia is that the need to transport

compressed gas could be reduced or eliminated

by maintaining anesthetized casualties on room

air.

Minor Procedures and Transport. Ketamine can

be used in a wide range of situations encountered in

a field hospital. It probably is most effective in

providing anesthesia for peripheral or surface procedures. For minor operations such as debridement,

incision and drainage, and delayed primary closure, ketamine may be delivered as a bolus of 0.25 to

1.0 mg/kg, administered intravenously, or 1 to 4

mg/kg, administered intramuscularly. These doses

are also appropriate for analgesia during transport.

Airway reflexes and respiratory drive generally

remain intact in this dose range. Repeat doses may

be required at 5- to 15-minute intervals. Another

approach is to administer a continuous infusion of

5 to 20 μg/kg/min throughout the procedure. A

similar dosage schedule is appropriate for analgesia during transport. Benzodiazepines in small

doses will attenuate psychic disturbances, although

these are seldom significant with low-dose

ketamine.17,33,36

For minor surgery such as superficial soft-tissue

debridement or brief genitourinary or general surgery, general anesthesia can be accomplished using

ketamine 2 mg/kg intravenously or up to 10 mg/kg

intramuscularly. Repeat doses may be titrated to

abolish purposeful movements or nystagmus. Care

must be taken to monitor airway adequacy at these

doses, and supplemental oxygen is prudent. However, this technique still represents a relatively safe

approach to general anesthesia in a setting where

skilled personnel and elaborate equipment or compressed gases may not be available. Emergence

reactions will pose a problem at these doses, and

administration of a benzodiazepine will necessitate

more expert and vigilant care of the airway. Recovery time may take up to 45 minutes or longer,

especially if other anesthetic agents are used. Recovery from low-dose ketamine should be well under 30 minutes.25,37

Major Procedures. In patients suffering from

hypovolemia, severe anemia, or cardiovascular compromise, ketamine is an excellent choice for an

induction agent.23,28 While most intravenous induction agents cause hypotension, ketamine generally

will preserve blood pressure and cardiac output in

casualties in hypovolemic shock. Doses for induction of anesthesia are in the range of 1 to 2 mg/kg

intravenously or 4 to 6 mg/kg intramuscularly,

with decreased doses as appropriate when the patient is severely ill or in profound shock. Ketamine

is suitable for use in patients with full stomachs,

with the usual precautionary measures such as application of cricoid pressure and preoxygenation.

In the previously healthy, normovolemic patient,

ketamine induction may result in undesired blood

pressure elevation.

Ketamine can be used to maintain surgical anesthesia for major intraabdominal or intrathoracic

cases in combination with inhaled agents, particularly when hypotension limits the dosage of the

latter. Following induction, ketamine may be administered intravenously at 15- to 30-minute intervals, as needed, in boluses of 0.5 to 2.0 mg/kg. The

patient breathes a low dose of a volatile agent delivered via a field anesthesia machine or similar equipment, or the agent is given via positive-pressure

ventilation as necessary. If available, nitrous oxide

may be used to supplement ketamine maintenance.

A benzodiazepine administered during the operation

will reduce the incidence of postoperative delirium.17

Alternatively, a continuous ketamine infusion

will maintain surgical anesthesia.38–40 Use in combination with another agent will minimize the total

ketamine dose. Usually, 10 to 30 μg/kg/min with

50% to 70% nitrous oxide or a background volatile

agent will be sufficient. Again, a benzodiazepine is

recommended. An antisialagogue such as atropine

or glycopyrrolate will minimize salivation and upper-airway secretions.

Total Intravenous Anesthesia With Ketamine.

Finally, when compressed gases are not available,

ketamine can act as the primary agent in a total

intravenous anesthetic for major operations. The

best results have been obtained using a benzodiazepine for induction, followed by intubation using a

muscle relaxant, and then initiation of a ketamine

infusion (see Table 10-3) in the range of 20 to 40 μg/

kg/min, with controlled ventilation on air or oxygen-enriched air, as available. Although this tech-
Intravenous Anesthesia

221

nique has been used successfully for abdominal

surgery with little postoperative psychic disturbance, recovery time is likely to be prolonged.35 In

the injured casualty in hypovolemic shock, induction is probably more safely achieved using ketamine

rather than a benzodiazepine.

Ketamine for Pediatric Anesthesia. The treatment of combat casualties includes the care of civilians, among whom may be injured children.

Ketamine has long been a mainstay in pediatric

anesthesia, and it adapts well for use in the field. In

a child, an intramuscular dose of 5 to 10 mg/kg will

provide surgical anesthesia that will last from 10 to

30 minutes. Lower doses may provide adequate

sedation for brief, minor procedures. A sedating

intravenous dose would be 0.25 to 0.5 mg/kg. Production of significant upper-airway secretions accompanies the use of this agent in children and

necessitates the use of an anticholinergic drug (eg,

atropine or glycopyrrolate). Although airway reflexes and respiratory drive are generally well preserved, close attention must be paid to adequacy of

ventilation, as is done in any case of general anesthesia or deep sedation. The incidence of postoperative psychic disturbances in children is thought

to be lower than that in adults.17,23

ANXIOLYTIC AND AMNESTIC AGENTS

Anxiety and fear are very common in the

preoperative patient, and even more so in wounded

soldiers. Severe anxiety may cause significant

tachycardia, hypertension, and increased respiratory rate. Oxygen consumption and carbon dioxide

production are increased. Such patients may also

be uncooperative, irrational, or combative. Finally,

serious psychic trauma may occur in some patients

due to their recall of events in the operating room—

during resuscitative efforts or surgery or both. In

addition to the humane considerations, physiological benefits can be attained if the casualty’s fear and

anxiety are reduced. The agents discussed in the

following section have proven useful for producing

amnesia to both preoperative and intraoperative

events, and some are potent anxiolytics as well. In

high doses, some of these agents have a hypnotic

effect and may be used to induce an anesthetic state.

Benzodiazepines

The drugs of this class that are most likely to see

clinical use during wartime are diazepam (Valium,

manufactured by Roche Products, Inc., Manati,

Puerto Rico) and midazolam (Versed, manufactured

by Roche Laboratories, Nutley, N.J.).

Pharmacology

All the benzodiazepine drugs possess similar

anxiolytic, sedative, hypnotic, amnestic, anticonvulsant, and muscle-relaxant properties.11 While the

pharmacodynamics (ie, what the drug does to the

body) of diazepam and midazolam are very similar,

their pharmacokinetics (ie, what the body does to

the drug) are quite different.

Diazepam has a distribution half-life of 30 to 60

minutes and an elimination half-life of 20 hours or

more. Its primary metabolite is active and has an

elimination half-life of 41 to 139 hours. The clinical

effects of an intravenous diazepam dose are seen

within 1 to 2 minutes and last from 1 to 3 hours, with

widely variable individual responses.

Midazolam is water soluble, more potent than

diazepam, and has no active metabolites.41 Distribution half-life is 7 to 15 minutes, and elimination

half-life is 2 to 4 hours. Its higher potency and

shorter duration of clinical action make midazolam

particularly attractive in situations where a benzodiazepine drug is indicated.

Physiological Effects

Central Nervous System. Diazepam and

midazolam are potent anxiolytics, acting on the

centers in the central nervous system that generate

fear, anxiety, and aggression. In addition to reducing anxiety, these drugs provide excellent amnesia.

In high doses, either drug can be used as an anesthetic induction agent (see Table 10-2), although

their primary usefulness is as sedative or anxiolytic

agents or both. Recovery from an induction dose of

midazolam or diazepam is likely to take longer than

is practical in a field hospital.

The benzodiazepines raise the seizure threshold.

Thus they confer central nervous system protective

effects to the patient who receives large (and potentially toxic) amounts of local anesthetic agent during regional anesthetic techniques, as well as to the

patient with brain injury from head trauma.

Cardiovascular System. In otherwise healthy

patients, minimal cardiovascular effects are seen

with diazepam or midazolam.11,41 Mean arterial

pressure is typically decreased from 0% to 15%, and

moderate increases in heart rate are seen when

midazolam is used (0.15 mg/kg administered intra-
Anesthesia and Perioperative Care of the Combat Casualty

222

venously over 15 s) for induction of anesthesia. This

is considerably less hypotension than is routinely

seen when sodium thiopental is used as an induction

agent. When midazolam is given in a dose of 0.3

mg/kg, hemodynamic changes are similar to those

seen with thiopental at a dose of 4.0 mg/kg. Compared with diazepam, midazolam produces a greater

decrease in blood pressure, and a slightly greater

decrease in systemic vascular resistance.42

Combining other anesthetic drugs with diazepam

or midazolam in a healthy patient may cause more

hemodynamic depression than either agent used

alone. In patients with no preexisting heart disease,

combining benzodiazepines with narcotics is necessary to prevent hemodynamic changes associated

with laryngoscopy and intubation.41

Respiratory System. An induction dose of

midazolam significantly reduces the ventilatory

response to carbon dioxide and produces respiratory depression. This effect has a slower onset and

lasts longer than that obtained with thiopental.43

Continual vigilance and monitoring will be required in the trauma patient who has received a

benzodiazepine drug, particularly when other potent anesthetic drugs have been administered. Postoperative respiratory depression in such a patient is

a very real danger. Death secondary to respiratory

arrest is a preventable event when the patient is

adequately monitored.

Clinical Use

Although diazepam may be used for induction of

anesthesia (at a dose range of 0.5–1.0 mg/kg), its

relatively prolonged clinical effects limit its clinical

usefulness as a primary anesthetic agent. The drug

is poorly soluble in aqueous solution and is supplied in an ethylene glycol carrier solution. This

causes a troublesome stinging or burning sensation

on injection, particularly with the relatively large

doses needed for induction of anesthesia. The true

usefulness of diazepam in wartime surgery is as an

adjunct to other anesthetic agents and techniques,

and in allaying anxiety in the perioperative period.

Sedation and anxiolysis are achieved with diazepam

by titrating to desired effect, with a typical total

dose range of 5 to 10 mg.

Because of its rapid onset of action and relatively

short duration of action (60–90 min following an

induction dose), midazolam can be used as an alternative to the barbiturates for induction of anesthesia for surgery that is expected to last 2 hours or

longer. The dose is 0.15 to 0.3 mg/kg when used for

this purpose. When surgery lasts less than 60 to 90

minutes, the anesthesia provider can expect to see

significant postoperative respiratory depression

with this induction regimen. When titrated to effect

with 0.5 to 1.0 mg intravenous boluses, midazolam

is an excellent anxiolytic and produces profound

amnesia, making it a useful agent in the patient

receiving a regional anesthetic technique.

As has already been mentioned, ketamine frequently causes vivid dreaming, nightmares, hallucinations and other emergence phenomena. The

incidence of these undesirable effects is significantly reduced when a benzodiazepine is administered concomitantly. A useful regimen is diazepam

0.15 mg/kg administered intravenously 5 minutes

prior to induction with ketamine. Midazolam 0.075

mg administered intravenously may be used in

place of diazepam. Since ketamine has proven to be

a very popular field anesthetic agent during recent

conflicts, the benzodiazepine drugs will no doubt

be useful adjuncts to its use.

Scopolamine

Scopolamine is a naturally occurring drug, obtained from plants of the belladonna family. Other

drugs in this class include atropine and glycopyrrolate (Robinul, manufactured by A. H. Robins

Co., Richmond, Va.). All of these agents will reduce

salivation and upper airway secretions. Scopolamine possesses unique features that make it useful

in trauma anesthesia.

Physiological Effects

Central Nervous System. Scopolamine crosses

the blood–brain barrier and depresses the central

nervous system. In therapeutic doses (0.4 mg administered intravenously), it causes drowsiness,

euphoria, amnesia, fatigue, and dreamless sleep.

Scopolamine is 9-fold more potent than atropine as

an amnestic agent. (Another antimuscarinic agent,

glycopyrrolate, does not cross the blood–brain barrier. This makes it useful when parasympathetic

inhibition is desirable but the potential central nervous system effects of scopolamine are not).

Cardiovascular System. Drugs with antimuscarinic effects inhibit the actions of acetylcholine on

the postganglionic cholinergic nerves of the parasympathetic nervous system, and thus reduce or

inhibit parasympathetic tone. This is seen clinically

as an increase in heart rate (usually lasting less than

30 min).
Intravenous Anesthesia

223

Clinical Use and Contraindications

The severely traumatized battlefield casualty is

likely to be suffering from hemorrhagic shock. The

nature of the wounds may dictate immediate surgery, even as the anesthesia team is resuscitating

with airway management and intravenous fluid

therapy. Because of adverse hemodynamic effects,

it is unlikely that such a casualty would tolerate the

administration of most of the intravenous anesthetic agents we have discussed in this chapter.

Scopolamine (0.4 mg administered intravenously),

with its minimal cardiovascular effects and its desirable amnestic qualities, may be the only safe

anesthetic drug in this circumstance. As resuscitative efforts proceed and the patient’s hemodynamic

status stabilizes, additional anesthetic agents may

be judiciously titrated.

The central nervous system effects of scopolamine are not absolutely reliable, and fully conscious

patients may find them unpleasant. For this reason,

use of this drug should be reserved for the severely

traumatized and unstable patient, or in those cases

where drying of upper airway secretions is desirable (eg, if the casualty requires nasal and oral

surgical procedures). If they are available, atropine

or glycopyrrolate are better choices for the latter

indication.

Droperidol

Droperidol is a major tranquilizer of the

butyrophenone class with antipsychotic activity and

potent antiemetic effects.

Physiological Effects

Central Nervous System. Droperidol may be

used in combination with an opioid narcotic to

induce a state of neuroleptanalgesia or neuroleptanesthesia. Such states are characterized by

altered awareness, sedation, and, ultimately, unconsciousness. During the state of neuroleptanalgesia, the patient remains conscious but may

tolerate short, painful surgical procedures.

Droperidol is also an excellent centrally acting

antiemetic drug.

Cardiovascular System. Droperidol produces

mild α-adrenergic blockade with peripheral vascular dilation. The resultant decrease in systemic

vascular resistance is seen clinically as a fall in

blood pressure. This effect may be very significant

in the hypovolemic patient.

Clinical Use and Contraindications

The onset of action of droperidol occurs in 3 to 10

minutes following intravenous (75 μg/kg) or intramuscular (150 μg/kg) injection. The full effect may

not be apparent for 30 minutes. With therapeutic

doses, the duration of sedative effect is 2 to 4 hours,

although alteration of consciousness may persist up

to 12 hours. Additionally, intravenous doses greater

than 100 μg/kg may result in prolonged postoperative somnolence.

When a neuroleptic technique is chosen, the

opioid agent most commonly used with droperidol

is fentanyl, generally in a ratio of 50 μg fentanyl per

2.5 mg droperidol. This combination is available

premixed and is called Innovar (manufactured by

Janssen Pharmaceutica Inc., Piscataway, N.J.). Nitrous oxide is frequently added to the neuroleptanalgesia regimen to induce unconsciousness and

neuroleptanesthesia. The effects of droperidol last

longer than the analgesic properties of fentanyl.

The result may be a patient who is outwardly calm,

yet is experiencing pain and mental agitation. A

therapeutic dose for sedation (when used alone for

this purpose) is 5 to 10 mg for a 70-kg individual.

Droperidol’s undesirable effects on blood pressure in therapeutic doses, as well as its unpleasant

and prolonged psychic effects, limit its usefulness

as an anesthetic agent. However, the drug is a

potent antiemetic in doses that cause minimal sedation (0.625–1.25 mg administered intravenously,

which is 0.25–0.5 mL of the standard preparation).

The awake patient with minimal postoperative anesthetic side effects (such as nausea and vomiting)

will be the easiest to care for with the limited resources of the field hospital recovery room.

ANESTHETIC AGENTS THAT PRODUCE ANALGESIA

Analgesia is a very desirable attribute of an anesthetic agent. However, many of the commonly used

intravenous anesthetic agents (including the barbiturates, etomidate, and propofol) have no analgesic

properties. Analgesic drugs may be used in combination with agents that produce unconsciousness.

The benefits of such combined regimens include

maintenance of surgical anesthesia with reduced

dosages of each drug, and residual postoperative

pain relief. This chapter deals primarily with the
Anesthesia and Perioperative Care of the Combat Casualty

224

opioid narcotic agents. However, it should be noted

that ketamine, which is an extremely useful anesthetic-induction agent, provides very potent analgesia in small intravenous bolus doses (5–10 mg).

Opioid narcotic agents are the most commonly used

analgesics. The term opioid refers to compounds

that bind to one or more subpopulations of opiate

receptors in the central nervous system. Most anesthesiologists classify the opioid drugs on the basis

of their primary effects at the opiate receptor site.

This classification scheme results in three primary

drug groups: the opioid agonists, the agonist–antagonists, and the antagonists. See Chapter 13,

Perioperative Pain Management, for a discussion of

the use of these agents purely for analgesia.

Opioid Agonist Drugs

The opioid agonist drugs commonly used

intraoperatively (either to supplement or to provide the primary anesthetic) include morphine,

meperidine, and the relatively recently discovered

phenylpiperidine derivatives, namely, fentanyl,

sufentanil, and alfentanil. While these agents differ

in potency and pharmacokinetics, they share the

important properties of dose-related analgesia as

well as respiratory depression.44

Because the combat medical corpsman may be

supplied with prefilled morphine syringes for

prehospital field use, it is imperative that the

preanesthetic evaluation of the patient should include whether the patient was medicated during or

prior to transport to the field medical facility. Failure to ascertain the dose given may lead to the need

for prolonged postoperative ventilatory support if

additional morphine or other opioid agonists are

given intraoperatively.

Physiological Effects

Central Nervous System. The opioid agonists

produce analgesia, sedation, euphoria, and a feeling of body warmth. In the absence of pain,

dysphoria rather than euphoria may be produced.

Analgesia is most effective when administered prior

to onset of the painful stimulus. Continuous, dull

pain is relieved more effectively than sharp, intermittent pain. These effects are a result of drug

interaction with opioid receptors in the brain and

spinal cord. Another important effect of the opioids

is stimulation of the central nervous system chemoreceptor trigger zone, producing nausea or emesis in

many patients.44

Cardiovascular System. Direct stimulation of

the medullary vagal nucleus may cause bradycardia following a dose of an opioid agonist.44 Compensatory sympathetic nervous system responses

are blunted, producing or contributing to orthostatic hypotension. Hypotension may also be seen

secondary to morphine-induced histamine release.45

This effect is widely variable, and can be mitigated

somewhat by slow administration, supporting intravascular volume, slight head-down position, and

prior administration of antihistaminic drugs.

Meperidine also causes histamine release, but

fentanyl and sufentanil do not.45

Meperidine is the only opioid drug with a direct

myocardial depressant effect (when given in large

doses). Also in contrast with the other opioid agonists, meperidine rarely causes bradycardia and

may, in fact, be associated with tachycardia. This

property probably reflects its structural similarity

to atropine. Like morphine, meperidine may interfere with compensatory sympathetic nervous system

reflexes. In analgesic doses, meperidine is associated

with hypotension more commonly than is morphine.

The principal advantages of fentanyl (and its

more recent analogs) are its maintenance of stable

hemodynamics due to the absence of histamine

release, the relative lack of direct myocardial depressant effects, and the suppression of the stress

responses to surgery.

Respiratory System. All opioid agonists depress

ventilation. This initially manifests clinically as a

decreased rate of breathing with maintenance of

tidal volume. With higher doses, tidal volume

diminishes as well. Thus, a dose-related increase in

the partial pressure of carbon dioxide in arterial

blood (PaCO2) is seen. It is important to note, however, that morphine and other opioid agonists may

actually lower PaCO2 values postoperatively in

some patients who have been breathing with small

tidal volumes because of pain. Pain is a natural

antagonist to the respiratory depressant action of

opioids.44

Respiratory depression in a casualty who has a

closed head injury is particularly dangerous. Because opioid narcotic agents depress the ventilatory response to carbon dioxide, increased PaCO2 in

the spontaneously breathing combat trauma victim

will cause increased intracranial pressure with potentially lethal consequences when head injuries

are present. Extreme caution must attend the use of

opioid narcotics in such patients.

Respiratory depression is also a problem when

these drugs are given in dosage ranges high enough
Intravenous Anesthesia

225

to produce unconsciousness or surgical anesthesia.

Because prolonged mechanical ventilatory support

will generally be impossible in the austere environment of the combat support hospital, pure narcotic

anesthetic techniques will not be useful. The utility

of the narcotic drugs will be as adjuncts to inhalational or intravenous anesthetic techniques, using

shorter-acting drugs that depress the respiratory

system less as the primary anesthetic agents.

Morphine

Morphine is the classic opioid agonist. Intravenous administration of morphine produces a peak

effect in about 20 minutes. This relatively slow

onset reflects prolonged penetration of the blood–

brain barrier by morphine, owing to its poor lipid

solubility. The elimination half-life is approximately

2 hours and is largely dependent on excretion by the

kidney following conjugation in the liver. A typical

intraoperative dose, when morphine is used as an

adjuvant agent for general anesthesia, is 0.1 to 0.2

mg/kg. The ideal dose will vary with the duration

of the operation. Excellent and relatively prolonged

postoperative analgesia generally results when this

regimen is used. When morphine is used as the

primary anesthetic agent, a dose of 1.0 to 2.0 mg/kg

is necessary. The inability to provide adequate

postoperative ventilatory support in the field medical environment severely limits the usefulness of

the latter technique. Side effects include nausea,

pruritus, and depressed ventilatory response to

carbon dioxide. When morphine is used with other

anesthetic agents, its respiratory depressant effects

are augmented. This necessitates careful titration

and monitoring in the operating room.

Meperidine

Meperidine (Demerol, manufactured by Sanofi

Winthrop Pharmaceuticals, New York, N.Y.) is an

older synthetic opioid agonist with one tenth the

potency of morphine. Although it has been supplanted by newer and better synthetic drugs for

intraoperative use in the United States, meperidine

may prove to be readily available in third-world

nations, and is still commonly used for analgesia

outside the operating room. A typical intramuscular dose for postoperative pain is 1 to 2 mg/kg. If

given via the intravenous route, this dose should be

reduced by half. Precautions for intraoperative and

postoperative meperidine use are similar to those

for morphine.

Fentanyl

Fentanyl (Sublimaze, manufactured by Janssen

Pharmaceutica Inc., Piscataway, N.J.) is a synthetic

opioid agonist that is 100-fold more potent than

morphine. It is supplied in a preparation of 50 μg/

mL. Fentanyl has a faster onset and shorter duration of action than morphine. Potency and onset are

related to the drug’s high lipid solubility, and the

shorter half-life reflects redistribution.44 Like

thiopental, repeated doses or continuous infusions

saturate inactive tissue sites, interfering with the

ability of redistribution to lower serum concentrations of the drug. The elimination half-life of fentanyl

is 200 minutes, which is actually longer than that of

morphine. This apparent contradiction is explained

by both redistribution of drug from the active site

and the greater volume of distribution of fentanyl.

Serum concentration is partially maintained by slow

re-uptake from inactive tissue sites.

Clinically, fentanyl has been popular in a wide

range of doses. One to two micrograms per kilogram is a useful analgesic dose; 3 to 10 μg/kg is a

useful dose range as an adjunct to other anesthetic

drugs for induction or maintenance of anesthesia.

Once again, prolonged postoperative respiratory

depression severely limits the utility of this latter

technique in most combat-support medical settings.

If intraoperative mechanical ventilation is available, fentanyl may be administered with a continuous-infusion technique. Following a loading dose

of 5 to 10 μg/kg (depending on the predicted length

of the surgery), a continuous infusion is begun and

maintained at 1 to 2 μg/kg/h. If the infusion is

stopped 20 to 30 minutes prior to the completion of

surgery, the patient will generally awaken promptly

with excellent residual analgesia. Used in this manner, fentanyl augments the effects of the volatile

anesthetic drugs, allowing the use of lower inspired

concentrations of these agents. This technique

should not be used unless the patient’s respirations

are controlled in the operating room.

The shorter duration of action of fentanyl (relative to morphine) allows greater ease of titration in

the clinical setting. The absence of histamine release in clinically relevant doses results in less dilation of the venous capacitance vessels, producing

less hypotension and a decreased need for temporary fluid supplementation.

Potential problems include persistent or recurrent respiratory depression. Fentanyl circulating in

the plasma may be secreted into and sequestered by

acidic gastric fluid, with subsequent reabsorption.
Anesthesia and Perioperative Care of the Combat Casualty

226

This reabsorbed fentanyl will once again act on the

central nervous system. Fentanyl may also become

trapped in poorly perfused areas of the lung during

general anesthesia. Washout of these areas as perfusion improves would also tend to increase the

plasma fentanyl level. Other potential problems are

bradycardia, which may become hemodynamically

significant in the traumatized patient, and truncal

rigidity. The latter can make controlled ventilation of

the patient quite difficult, necessitating the use of a

neuromuscular blocking agent to relax the chest

wall. The incidence and severity of both bradycardia

and truncal rigidity appear to be related to the rate of

administration, and each is readily managed with

the appropriate pharmacological intervention.

Sufentanil

Sufentanil (Sufenta, manufactured by Janssen

Pharmaceutica Inc., Piscataway, N.J.) is an analog

of fentanyl, with an elimination half-life of approximately 156 minutes. Its anesthetic potency is estimated to be 5- to 10-fold greater that of fentanyl.

This increased potency is a result of sufentanil’s

greater affinity for the opioid receptor.46 The greater

potency and more rapid onset of sufentanil make it

a more titratable drug than fentanyl. This reduces

the incidence and likelihood of tachycardia and

hypertension in response to painful stimuli. Side

effects and potential problems are the same as those

seen with fentanyl.

Like fentanyl, sufentanil is supplied in a strength

of 50 μg/mL. For analgesia, 5 to 10 μg administered

intravenously may be sufficient. Note that this is

0.1 to 0.2 mL of undiluted drug. Obviously, great

care is required when sufentanil is used in this way.

This dose may be repeated as necessary to achieve

adequate analgesia.

As an adjunct to general anesthesia, sufentanil

possesses all the advantages of fentanyl with respect to hemodynamic stability and suppression of

the stress response to surgery. It appears to be even

better than fentanyl in preventing or reducing the

hemodynamic response to endotracheal intubation.

When used as part of a balanced anesthetic technique, a useful starting dose of sufentanil is 0.5 to

1.0 μg/kg. As with fentanyl, a continuous infusion

may be established at a rate of 0.1 to 0.2 μg/kg/h.

Alfentanil

In contrast to sufentanil, alfentanil (Alfenta,

manufactured by Janssen Pharmaceutica Inc.,

Piscataway, N.J.), the fentanyl analog, is much less

potent than its parent compound. Alfentanil is

supplied in a strength of 500 μg/mL. It has one

tenth to one fifth the potency, one fourth the time to

onset of action, and about one third the duration of

action of fentanyl. The relatively fast onset and

short duration of alfentanil allow for excellent

titratability and make it very useful for shorter

surgical procedures and continuous infusions.

Alfentanil rapidly crosses the blood–brain barrier because it is almost entirely un-ionized at physiological pH.46 After an intravenous bolus, plasma

levels fall rapidly owing to both redistribution and

metabolism. Unlike most other drugs, alfentanil in

a continuous infusion does not produce a significant cumulative effect in the length of time that

most surgery requires. The elimination half-life is

about one half that of fentanyl. The clinical duration of action of this agent may be as little as 15

minutes following an intravenous bolus injection.

When used as part of a balanced anesthetic technique, a continuous infusion is recommended because of its short duration of action. Alfentanil, in

a dose of 150 to 300 μg/kg, will induce anesthesia in

less than 1 minute. An infusion rate of 25 to 150 μg/

kg/h, when combined with another amnestic sedative (such as a low-dose potent inhalational agent),

is effective for the maintenance of anesthesia and

will produce minimal cumulative drug effect. Such

a technique may prove to be very useful in the

combat medical facility.

Alfentanil shares with all of the fentanyl analogs

the potential for problems with respiratory depression and bradycardia.

Opioid Agonist–Antagonist Drugs

As the name implies, opioid drugs in this group

have both excitatory and inhibitory effects at opiate

receptor sites in the central nervous system. The

mixture of agonist and antagonist properties limits

somewhat their clinical usefulness when used as

the sole narcotic agents during general anesthesia.

A theoretical advantage of these drugs is that their

partial antagonist action may reduce the incidence

or degree of respiratory depression that is seen with

equivalent doses of pure opioid agonist agents.

However, this same mechanism limits the achievable degree of analgesia when agonist–antagonist

drugs are administered.

Clinical experience has shown that significant

respiratory depression remains a potentially serious side effect with these agents, despite their partial antagonist properties. They are most useful as

analgesic adjuncts to regional anesthetic procedures,
Intravenous Anesthesia

227

and in the recovery room. Another potential problem is triggering of the withdrawal syndrome in the

opioid-narcotic addicted patient.

Nalbuphine

The analgesic potency of nalbuphine (Nubain,

manufactured by Du Pont Multi-Source Products,

Garden City, N.Y.) is approximately the same (milligram for milligram) as that of morphine. Onset of

action is within 2 to 3 minutes following intravenous injection, with a duration of effect in the range

of 3 to 6 hours.

Respiratory depression may occur within the

usual dose range (generally 10–15 mg) for

preoperative sedation or analgesia. The degree of

respiratory depression is similar to that of an

equianalgesic dose of morphine. There is a ceiling

effect to the magnitude of respiratory compromise;

that is, depressed respiration does not become more

pronounced as the dose of nalbuphine is increased.

However, there also appears to be a ceiling effect to

the degree of analgesia achieved with increasing

doses of nalbuphine. What this means clinically is

that doses in excess of 0.15 mg/kg will confer no

greater respiratory depression or analgesia than

lower doses.44

Butorphanol

Butorphanol (Stadol, manufactured by Bristol

Laboratories, Evansville, Ind.) resembles nalbuphine

in its clinical usage and effects. It is approximately

5-fold more potent than morphine on a weight basis. Butorphanol may be given intramuscularly (1–

4 mg) or intravenously (0.5–2.0 mg). Duration of

analgesia is 3 to 4 hours. As with nalbuphine, an

analgesic and respiratory depressant ceiling effect

is seen.

Opioid Antagonist Drugs

Naloxone (Narcan, manufactured by Du Pont

Multi-Source Products, Garden City, N.Y.) is the

prototypical narcotic antagonist, with strong affinity for opiate receptors and almost no agonist effect.

In cases of opiate-induced respiratory depression

(such as might be seen following a relative overdose

of narcotic agent during general anesthesia), respiratory rate and tidal volume are promptly increased

following an intravenous dose of naloxone. However, the analgesic and sedative effects of these

drugs will also be antagonized. Thus, the dose of

naloxone should be carefully titrated in 0.1- to 0.2-

mg doses (for children, 0.01 mg/kg) at 2- to 3-

minute intervals until the desired effect is achieved.

The onset of action is rapid (within 2 min) following

intravenous injection and is only slightly longer via

the intramuscular route.

The clinical effects of naloxone last from 1 to 4

hours, depending on the dose given. The plasma

half-life is about 1 hour. Since the respiratory depressant effects of some opioid narcotics may persist longer than the naloxone dose administered,

personnel in the recovery room must be informed

whenever this drug is used in the operating room

prior to transport. Such a patient will require more

than usual vigilance in the recovery area to prevent

hypoventilation or apnea should the narcotic effect

outlast that of naloxone.

Naloxone possesses some undesirable side effects. The most serious potential problems include

increased intracranial pressure in the patient with a

head injury, hypertension, pulmonary edema,

dysrhythmias, and cardiac arrest.47

Naloxone (as well as the agonist–antagonist

drugs) may precipitate a moderate to severe withdrawal syndrome. The symptoms and signs of

acute narcotic withdrawal include irritability, nervousness, mental confusion, generalized pain, diaphoresis, abdominal cramping with diarrhea, nausea, and vomiting. This syndrome appears within 2

minutes of the administration of naloxone to a patient with narcotic dependency, and is self-limiting

owing to its short plasma half-life of approximately

60 minutes. Soldiers are not entirely exempt from

narcotic abuse, and this history must be obtained

preoperatively, if possible.

TECHNIQUES FOR USING INTRAVENOUS ANESTHETICS

causes severe pulmonary dysfunction and is potentially fatal. At the very least, such complications

require the allocation of scarce recovery and critical

care resources to treat what is nearly always a

preventable complication of general anesthesia. The

risk of regurgitation and aspiration is markedly

reduced when the trachea is intubated with a cuffed

Rapid-Sequence Intravenous Induction

Experience with battlefield casualties in Vietnam

showed that the majority of wounded soldiers have

undigested material in their stomachs at the time of

emergency surgery.1 Regurgitation and aspiration

of gastric contents into the tracheobronchial tree
Anesthesia and Perioperative Care of the Combat Casualty

228

further deterioration of the patient’s condition. A

rapid-sequence technique using succinylcholine

alone may be the safest alternative in such situations. In the worst case, even succinylcholine may

be dispensed with and the patient intubated through

cricoid pressure. Scopolamine 0.4 mg administered

intravenously may provide amnesia during the initial period of resuscitation.

Adjuvants to Inhalational Anesthesia

Following induction of anesthesia with an intravenous drug, surgical anesthesia must be maintained. Most commonly this will be accomplished

with a volatile anesthetic agent delivered by drawover vaporizer or a field anesthesia machine. If the

patient is to breathe spontaneously during the procedure, adjuvant drugs such as opioid narcotic

agents must be used with extreme caution to prevent respiratory arrest.

When inhalational anesthesia is being used as the

primary technique, the addition of a narcotic drug

is part of a balanced anesthetic, with the advantages

of lower total overall doses of individual anesthetic

drugs as well as residual postoperative analgesia

(Exhibit 10-2). Because of the respiratory depression that accompanies a balanced anesthetic technique, it is most useful in the field environment in

those cases during which the casualty’s respirations are to be manually controlled. Such instances

would include those there the casualties were undergoing thoracotomies, craniotomies, and major

intraabdominal procedures. A muscle relaxant drug

is an important component of the technique.

endotracheal tube. This must be accomplished

quickly, following the administration of (1) an intravenous anesthetic agent that causes a rapid loss

of consciousness and (2) a muscle relaxant with a

similar rapid onset of clinical action. Rapid-sequence induction of anesthesia is performed in a

definite sequence (Exhibit 10-1).

The intravenous agents that are most useful for

rapid-sequence induction of anesthesia include sodium thiopental, ketamine, and etomidate (see Table

10-2). The reader is encouraged to review the specific advantages and disadvantages of these agents.

The only currently available neuromuscular blocking agent with a fast-enough clinical onset time for

use in a rapid-sequence induction technique is

succinylcholine. The following are suggested dose

regimens for rapid-sequence induction of anesthesia in combat casualties:

• ketamine (1–2 mg/kg) immediately followed by succinylcholine (1–2 mg/kg);

• etomidate (0.2–0.4 mg/kg) immediately followed by succinylcholine, as above; and

• sodium thiopental (1–4 mg/kg) immediately followed by succinylcholine, as above.

Each of these drug regimens will typically provide good intubating conditions within 45 to 60

seconds. Dosages should be adjusted downward in

the hemodynamically unstable patient, particularly

when thiopental is being used.

Not uncommonly, a combat casualty may already

be unconscious and in a hypovolemic shock state. In

such cases, any of the above agents may cause

EXHIBIT 10-1

RAPID-SEQUENCE INDUCTION OF ANESTHESIA

1. The patient is given four to five large breaths of 100% oxygen by anesthesia mask.

2. Firm pressure is applied by an assistant with thumb and finger over the patient’s cricoid cartilage in the

anterior neck. (This compresses the esophagus between the vertebral column and cricoid ring to minimize

the risk of passive regurgitation of gastric contents into the posterior pharynx.)

3. The chosen anesthetic agent and muscle relaxant are administered.

4. When the patient is unresponsive and has lost his lid reflex, the larynx is visualized and the endotracheal tube is

passed into the trachea. The cuff is inflated. (During the interval prior to intubation, the patient must not be

ventilated by bag and mask, as air may be forced into the stomach, increasing the risk of regurgitation.)

5. The presence of bilateral equal breath sounds is confirmed. Only after this fifth step is completed should the

assistant release the cricoid pressure.
Intravenous Anesthesia

229

EXHIBIT 10-2

OPIOID NARCOTICS AS ADJUVANTS TO INHALATIONAL ANESTHESIA

• Morphine 0.1 to 0.2 mg/kg.

• Meperidine 0.5 to 1.0 mg/kg.

• Fentanyl 3 to 5 μg/kg on induction of anesthesia. Additional bolus doses of 50 μg/h or a continuous infusion

at 1 to 2 μg/kg/h are used for maintenance. Continuous infusions should be stopped 15 to 30 minutes before

the end of surgery. An alternative technique is to estimate the time of the proposed surgical procedure. The

projected time (in minutes) is divided by 10 and 15. The resulting values represent the fentanyl dose in μg/

kg to be administered prior to skin incision, after which no more is given.1 For example, during a 60-minute

procedure, 4 to 6 μg/kg of fentanyl may be given prior to skin incision.

• Sufentanil 0.5 to 1.0 μg/kg on induction. Additional bolus doses of 5 to 10 μg may be given every 20 to 30

minutes as necessary. If a continuous infusion is to be used, the dosage rate should be 0.1 to 0.2 μg/kg/h

following the loading dose. Stop the infusion approximately 30 minutes before the end of surgery.

• Alfentanil 20 to 60 μg/kg following 2 mg/kg thiopental provides good surgical anesthesia. Larger doses of

alfentanil (150–300 μg/kg) will induce anesthesia in less than 1 minute when used alone. Alfentanil’s

duration of action is quite short (as little as 15 min following a bolus injection). For longer cases, a continuous

infusion is necessary to maintain anesthesia. The infusion rate should be set at 25 to 150 μg/kg/h, and can

be continued until the end of surgery. The patient can be expected to awaken promptly, but residual

analgesia will be relatively short-lived.

1. Ross, AL. How to give an anaesthetic using intravenous analgesics: An alternative from California. Can

Anaesth Soc J. 1983;30:259-260.

When spontaneous ventilation is to be maintained during general anesthesia for surgery outside the major body cavities, narcotic agents may be

administered cautiously as the case is nearing

completion. A useful regimen is to reduce slightly

the percentage of inspired concentration of the inhalational anesthetic agent. Morphine 0.5 to 1.0 mg

is then administered. This is repeated at about 10-

minute intervals, to a total morphine dose of 0.1 to

0.2 mg/kg. Respiratory rate and other vital signs

must be carefully monitored. Ideally, the last morphine dose is given and the inhalational agent completely turned off 10 to 15 minutes before the end of

the procedure. The result is a patient who is spontaneously ventilating with excellent analgesia. This

technique works best when the patient is breathing

50% to 60% nitrous oxide, which is shut off as the

last skin sutures are in place. Fentanyl may be

substituted for morphine and used in a similar

fashion, to a final dose of 3 to 5 μg/kg.

Total Intravenous Anesthesia

In contrast to regional techniques and general

anesthesia using inhaled gases, total intravenous

anesthesia using a single agent seems suited to

battlefield use, owing to its relative simplicity (see

Table 10-3). Since its introduction in 1970, ketamine

has been touted as such an agent. Although ketamine

has some untoward side effects, its tendency to

preserve blood pressure and airway reflexes make

it a very useful drug in the field (see the foregoing

section on ketamine in this chapter). It remains the

only available intravenous medication that can serve

as the sole agent in a general anesthetic.17 Its use in

this manner is described below.

It is conceivable that shortages of various anesthetic agents may occur in forward medical units

during wartime. If inhalational anesthetic agents

become scarce or unavailable, alternative techniques

will become necessary for maintenance of surgical

anesthesia. Even in the absence of such shortages,

total intravenous anesthesia may occasionally be

the technique of choice for brief surgical procedures. Total intravenous anesthesia is possible

using a variety of techniques (Exhibit 10-3).

Adjuvants for Regional and Local Anesthesia

For brief, minor surgical procedures, profound

anesthetic depth and complicated techniques are

not always necessary. If the procedure can be per-
Anesthesia and Perioperative Care of the Combat Casualty

230

EXHIBIT 10-3

TECHNIQUES FOR TOTAL INTRAVENOUS ANESTHETICS

• Ketamine. An induction dose of ketamine 1.0 to 2.0 mg/kg is preceded by midazolam 1 to 2 mg (or diazepam

5–10 mg). Following induction, a continuous infusion is maintained at 20 to 50 μg/kg/min (2–4 mg/min for

a 70-kg soldier). At the lower end of the dosage spectrum, spontaneous ventilation is possible. However,

regurgitation and aspiration are still risks. Therefore, in acutely injured patients, the airway should be

protected with an endotracheal tube. Midazolam or diazepam will reduce or eliminate emergence phenomena such as unpleasant dreams and hallucinations. When a neuromuscular blocking agent is used, the

maintenance dose of ketamine may be reduced somewhat.

• Etomidate. An induction dose of etomidate 0.2 to 0.4 mg/kg is given, followed by a maintenance dose of 40

to 100 μg/kg/min. After 10 minutes, this is reduced to 10 to 40 μg/kg/min. Since etomidate has no analgesic

properties, a narcotic (such as fentanyl 3 to 5 μg/kg) may be added to the regimen. For a 70-kg patient, these

maintenance doses are 170 to 400 mg/h for the first 10 minutes, followed by a rate of 40 to 170 mg/h. The

combination of etomidate, a narcotic agent, and a neuromuscular blocking agent can produce acceptable

surgical anesthesia. The infusion should be discontinued 15 to 30 minutes before the end of surgery.

• Sodium Thiopental. Incremental doses of sodium thiopental (1–2 mg/kg) may be titrated to onset of

unconsciousness. In this way, spontaneous ventilation may be preserved. This technique is useful for very

short procedures and to “smooth” the patient’s emergence from inhalational anesthesia. Due to its cumulative

central nervous system– and cardiopulmonary-depressant effects, however, thiopental must be administered

judiciously. For a surgical case that will last longer than 20 to 30 minutes, a continuous infusion may be

prepared by putting 1 to 2 g of thiopental in 250 mL of 5% dextrose in water. Following an induction dose of

2 to 4 mg/kg, a continuous infusion is maintained at 0.1 mg/kg/min. This infusion should be supplemented

with an intravenous narcotic and is not recommended unless the patient’s respirations are controlled.

• Propofol. Following an induction dose of propofol 2.0 to 3.0 mg/kg, a continuous infusion of 0.1 to 0.2 mg/

kg/min (6–12 mg/kg/h) is started. This dose may be reduced by one half or more for critically ill or debilitated

patients.

• Alfentanil. An induction dose of alfentanil 150 to 300 μg/kg will induce general anesthesia. A continuous

infusion should be set to run at 25 to 150 μg/kg/h for maintenance. Because alfentanil may produce chestwall rigidity and will definitely cause respiratory depression, the patient should be ventilated mechanically

when this technique is used.

formed under local anesthesia, intravenous agents

such as the benzodiazepines may be useful in allaying anxiety. Small, intravenous bolus doses of

thiopental (1–2 mg/kg) or etomidate (0.1 mg/kg)

will not provide analgesia, but may alter consciousness sufficiently to allow a short, painful procedure. If the patient has had no oral intake for at least

6 hours, aspiration risk with these techniques should

be minimal. If he has eaten recently, any druginduced blunting of the airway and gag reflexes

should be avoided unless the trachea is protected

with an endotracheal tube.

Ketamine is very useful for short procedures in

which deep general anesthesia is not required. Incremental bolus doses of 5 to 10 mg provide intense

analgesia and altered consciousness. The opioid

narcotic agents can also be used in these types of

cases. They are most effective if given before the

painful stimulus. Because they cause more blunting of spontaneous respiration, they allow somewhat less flexibility in dosing than ketamine.

Small-bolus injections of an opioid narcotic drug

may be useful in this setting for producing sedation

and supplying additional analgesia.

SUMMARY

An impressive number of intravenous anesthetic

drugs are available to the anesthesiologist in civilian practice. The wartime anesthesia provider, however, may have to make do with a more limited drug

repertoire. It is possible that many physicians and

nurses who have little or no training in the field of

anesthesiology will be called on to assist in providing this service in battlefield hospitals.
Intravenous Anesthesia

231

While the combat anesthesia provider may not

have access to all of the anesthetic agents described

in this chapter, at least one or two agents for each

anesthetic indication will almost certainly be available. Thus, only thiopental and ketamine may be

available for induction of anesthesia. For analgesia,

morphine or fentanyl may be the only drugs in the

pharmacy. Perhaps one of the benzodiazepines will

be available as well. Whatever the contents of the

drug locker, the wartime anesthesia provider must

have a rational plan of action for each casualty, and

should know how to use safely the intravenous

anesthetic agents available in the medical treatment

facility.

REFERENCES

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2. Courington FW. Anesthesia at the battlefield: The present and the future. Sem Anesth. 1988;7:26–32.

3. Halford FJ. A critique of intravenous anesthesia in war surgery. Anesthesiology. 1943;4:67–69.

4. Adams RC, Gray HK. Intravenous anesthesia with pentothal sodium in the case of gunshot wound associated

with accompanying severe traumatic shock and loss of blood: Report of a case. Anesthesiology. 1943;4:70–73.

5. The question of intravenous anesthesia in war surgery. Anesthesiology. 1943;4:74–77. Editorial.

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7. Papper EM, Sheehan WC. Anesthesiology in military medicine. Anesthesiology. 1943;4:619–624.

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517–519.

9. Bull PT, Merrill SB, Moody RA, et al. Anaesthesia during the Falklands campaign: The experience of the Royal

Navy. Anaesthesia. 1983;38:770–775.

10. Turcant A, Delhumeau A, Premel-Cabic A, et al. Thiopental pharmacokinetics under conditions of long-term

infusion. Anesthesiology. 1985;63:50–54.

11. White PF. What’s new in intravenous anesthetics. Anesth Clin N Am. 1988;6:297–318.

12. Brussel T, Theissen JL, Vigfusson G, Lunkenheimer PP, Van Aken H, Lawin P. Hemodynamic and cardiodynamic

effects of propofol and etomidate: Negative inotropic properties of propofol. Anesth Analg. 1989;69:35–40.

13. Giese JL, Stanley TH. Etomidate—a new intravenous anesthetic induction agent. Pharmacotherapy. 1983;3:251–258.

14. Milde LM, Milde JH, Michenfelder JD. Cerebral functional, metabolic, and hemodynamic effects of etomidate

in dogs. Anesthesiology. 1985;63:371–377.

15. Sebel PS, Lowdon, JD. Propofol: A new intravenous anesthetic. Anesthesiology. 1989;71:260–277.

16. Doze VA, Westphal LM, White PF. Comparison of propofol with methohexital for outpatient anesthesia. Anesth

Analg. 1986;65:1189–1195.

17. White PF, Way WL, Trevor AJ. Ketamine—its pharmacology and uses. Anesthesiology. 1982;56:119–136.

18. Corssen G, Domino E. Further pharmacologic studies and first clinical experience with phencyclidine derivative

Cl-581 (ketamine). Anesth Analg. 1966;45:29–39.

19. Ontani M, Kikuchi H, Kitahata LM. Effects of ketamine on nociceptive cells in the medial medullary reticular

formation of the cat. Anesthesiology. 1979;51:414–417.
Anesthesia and Perioperative Care of the Combat Casualty

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20. Kitahata LM, Taub A, Kosaka Y. Lamina-specific suppression of dorsal-horn unit activity by ketamine

hydrochloride. Anesthesiology. 1973;38:4–11.

21. Vincent JP, Corey D. Kamenka JM. Interaction of phencyclidines with the muscarinic and opiate receptors of the

central nervous system. Brain Res. 1972;152:176–182.

22. Morgan M, Loh L, Singer L, Moore PH. Ketamine as the sole anesthetic agent for minor surgical procedures.

Anaesthesia. 1971;26:158–165.

23. Boulton TB. Twenty years of dissociative anesthesia with ketamine (Cl-581): Its origin and present significance.

Surv Anesth. 1987;5:62–67.

24. Kothary SP, Zsigmond EK. A double-blind study of the effective antihallucinatory doses of diazepam prior to

ketamine anesthesia. Clin Pharm Ther. 1977;21:108–109.

25. Hatano S, Nishiwada M, Matsumaura M. Ketamine–diazepam anaesthesia for abdominal surgery: A review of

1000 cases with continuous “micro-mini” drip administration technique. Anaesthesia. 1978;27:172–182.

26. Waxman K, Shoemaker WC, Lippman M. Cardiovascular effects of anesthetic induction with ketamine. Anesth

Analg. 1980;59:355–358.

27. Bond AC, Davies CK. Ketamine and pancuronium for the shocked patient. Anaesthesia. 1974;29:59–62.

28. Longnecker DE, Sturgill BC. Influence of anesthetic agent on survival following hemorrhage. Anesthesiology.

1976;45:516–521.

29. Zsigmond EK, Kothary SP, Martinez OA. Diazepam for prevention of the rise in plasma catecholamines caused

by ketamine. Clin Pharm Ther. 1974;15:223–224.

30. Way WL, Trevor AJ. Pharmacology of intravenous nonnarcotic anesthetics. In: Miller RD, ed. Anesthesia. New

York, NY: Churchill-Livingstone; 1986: 813–817.

31. Lundy PM, Gowdy CW, Colhoun FH. Tracheal smooth muscle relaxant effects of ketamine. Br J Anaesth.

1974;46:333.

32. Carmichael GLM. Anaesthesia under civil war conditions. Anaesthesia. 1981;36:1077–1088.

33. Jowitt MD, Knight RJ. Anaesthesia during the Falklands campaign: The land battles. Anaesthesia. 1983;38:776–783.

34. Idvall J, Ahlgren I, Aronsen KF, Stenberg P. Ketamine infusions: Pharmacokinetics and clinical effects. Br J

Anaesth. 1979;51:1167–1172.

35. Barclay A, Houlton PC, Downing JW. Total intravenous anaesthesia: A technique using flunitrazepam,

ketamine, muscle relaxants and controlled ventilation of the lung. Anaesthesia. 1980;35:287–290.

36. Bion JF. An anaesthetist in a camp for Cambodian refugees. Anaesthesia. 1983;38:798–801.

37. White PF, Dworsky WA, Horai Y, Trevor AJ. Comparison of continuous infusion fentanyl or ketamine versus

thiopental: Determining the mean effective serum concentrations for outpatient surgery. Anesthesiology.

1983;59:564–569.

38. Bion JF. Infusion analgesia for acute war injuries: A comparison of pentazocine and ketamine. Anaesthesia.

1984;39:560–564.

39. Kamm GD, Bewes PC. Ketamine anaesthesia by continuous intravenous drip. Trop Doct. 1978;8:68–72.

40. Lilburn JK, Dundee JW, Moore J. Ketamine infusions: Observations on technique, dosage and cardiovascular

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Neuromuscular Blocking Agents

235

Chapter 11

NEUROMUSCULAR BLOCKING AGENTS

RICHARD B. HECKER, D.O.*; JAMES B. STEVENS, M.D.†; AND GERARD F. MELANSON, M.D.‡

INTRODUCTION

NEUROMUSCULAR MONITORING TECHNIQUES

Single Twitch

Train-of-Four

Tetanic Stimulation

Double-Burst Stimulation

Clinical Assessment

INDICATIONS FOR NEUROMUSCULAR BLOCKADE

TYPES OF MUSCLE RELAXANTS

Succinylcholine Chloride

Nondepolarizing Agents

COMPLICATIONS OF NEUROMUSCULAR BLOCKADE

SUMMARY

*Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200;

Clinical Assistant Professor of Anesthesiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7834,

and The Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799

†Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200;

Clinical Assistant Professor of Anesthesiology, The University of Texas Health Science Center at San Antonio, Texas 78284-7834

‡Major, Medical Corps, U.S. Army; Fellow in Multidisciplinary Critical Care Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas

78234-6200
Anesthesia and Perioperative Care of the Combat Casualty

236

INTRODUCTION

Fig. 11-1. The neuromuscular junction. Reprinted with

permission from Shorten G. Neuromuscular blockade.

In: Davison JK, Eckhardt WF III, Perese DA, eds. Clinical

Anesthesia Procedures of the Massachusetts General Hospital.

4th ed. Boston, Mass: Little, Brown; 1993: 152.

Nerve axon

Myelin sheath

Mitochondria ACh-containing

vesicles

Active

zone

Synaptic cleft

Muscle

membrane

ACh esterase

Myofibrils

ACh

receptors

Mitochondria

The primary reason for administering neuromuscular blocking agents to casualties with traumatic

injuries is to permit the airway to be secured with

endotracheal intubation and mechanical ventilation. Because battlefield injuries can cause inadequate ventilation and oxygenation, intubation is

often required. Many casualties with traumatic

injuries have an altered level of consciousness and

are at risk for aspiration of stomach contents because they are unable to protect the airway. On

occasion, the casualty may simply be so confused and

uncooperative that intubation with sedation and

muscle relaxation may be required to care for him.

The first description of the clinical use of neuromuscular blockade was reported in 1932, when dTubocurarine was administered to control the

muscle spasms of tetanus.1 Since then, the pharmacology and clinical use of neuromuscular blocking

agents, commonly referred to as muscle relaxants,

have been greatly expanded. Today, these drugs

are frequently used in surgery, the intensive care

unit, and the emergency department. This chapter

discusses the mechanisms of action, pharmacodynamics, uses, and complications of the most common neuromuscular blocking agents.

Classically, neuromuscular transmission is

viewed as the release of the neurotransmitter substance acetylcholine at the motor nerve terminal in

response to the neural action potential (Figure 11-1).

A cationic channel protein on the postjunctional

membrane possesses nicotinic cholinergic receptor

sites. When these sites are occupied by acetylcholine or a suitable agonist, the receptor channel protein undergoes conformational change. This causes

an influx of sodium ions and a corresponding efflux

(although of lesser magnitude) of potassium ions.

A smaller number of calcium ions then pass inward

with the sodium, with a change in the endplate

potential. Simultaneous opening of approximately

200,000 nicotinic receptor channels in response to

the evoked release of acetylcholine generates a motor

endplate potential. If this change in potential is of

sufficient magnitude, the voltage-gated sodium ion

channels of the adjacent muscle membrane open,

and a large number of sodium ions pass into the

interior of the cell, which depolarizes the cell. In

some manner, this process is coupled to the activation of the contractile mechanism.2

 In addition to

this mechanism, another population of cholinergic

receptors appears to exist on the motor nerve terminal itself. Their physiological role is obscure, but

their inactivation reduces the amount of acetylcholine that is released in response to a nerve impulse.

Through a combination of acetylcholine reuptake

and local degradation within the synaptic cleft by

the enzyme acetylcholinesterase, muscle repolarization occurs and the opportunity for contraction

is restored. A second nonspecific plasma enzyme,

pseudocholinesterase (ie, plasma cholinesterase), is

also involved in the breakdown of acetylcholine

and acetylcholine-like molecules.

It is customary to consider neuromuscular blocking agents in two groups: the depolarizing and the

nondepolarizing agents. Depolarizing agents, of which

succinylcholine is by far the best known, resemble

acetylcholine stereochemically and mimic its action

at the neuromuscular junction, causing depolarization of the endplate and adjacent muscle membrane, with clinically evident muscle fasciculations.

The neuromuscular junction remains depolarized

until succinylcholine diffuses away from the receptor site. Breakdown of succinylcholine occurs in a

two-stage process away from the receptor site:
Neuromuscular Blocking Agents

237

1. pseudocholinesterase hydrolyzes succinylcholine to choline and succinylmonocholine (which has weak depolarizing relaxant activity), and

2. succinylmonocholine slowly breaks down

to choline and succinic acid by the actions

of both acetylcholinesterase and pseudocholinesterase.

Low pseudocholinesterase levels, drug-induced

inhibition of cholinesterase activity, or the possession of a genetically atypical enzyme may be associated with prolonged neuromuscular blockade following the use of succinylcholine.

Nondepolarizing agents, on the other hand, act

by passively binding acetylcholine receptor sites

and thereby prevent their occupancy by acetylcholine. Because nondepolarizing agents act by blocking at the neuromuscular junction, muscle endplate

depolarization and clinical fasciculations are not

seen. The nondepolarizing agents are quaternary

ammonium compounds that include two major categories: the steroid-based derivatives and the

benzylisoquinoline series. Recovery from neuromuscular junction blockade occurs spontaneously

but can be accelerated by the use of pharmacological agents that inhibit acetylcholinesterase, which

therefore increases the availability of acetylcholine

to compete for the binding site. Theoretically, experimental research drugs such as 4-aminopyridine

can presynaptically increase the amount of acetylcholine and thereby competitively reverse the blockade caused by nondepolarizing agents. Currently,

however, only the anticholinesterase agents are used

clinically to antagonize neuromuscular junction

blockade.

NEUROMUSCULAR MONITORING TECHNIQUES

It is important to emphasize that monitoring of

neuromuscular function should be employed whenever neuromuscular blocking agents are used. The

military anesthesiologist should consider four main

questions when using neuromuscular blocking

agents:

1. Is the blockade adequate?

2. Is the blockade excessive?

3. Can the blockade be reversed?

4. Is the blockade fully reversed?

Although there are many ways to stimulate a

peripheral nerve, a typical commercially available

hand-held peripheral nerve stimulator should

provide the ability to choose stimulation by the

single twitch, train-of-four (TOF), tetanic, and

double-burst methods (Figure 11-2). The most

commonly recommended method to monitor

neuromuscular function is to observe the contraction of the fingers (adductor pollicis and flexor

digitorum muscles) in response to electrical stimulation of the ulnar nerve at the wrist or elbow

(Figure 11-3). Other areas may be stimulated, such

as the facial nerve or the peroneal or posterior tibial

nerves of the lower extremity (Figures 11-4 and

11-5). The magnitude of the muscle contraction

response can be a rough gauge to monitor neuromuscular blockade. It is important to emphasize

that direct muscle stimulation should be avoided,

as this can be mistaken for the responses seen with

nerve stimulation.

Fig. 11-2. The MiniStim is a portable, battery-operated,

adjustable-amplitude, hand-held peripheral nerve stimulator. Photograph: Courtesy of Life-Tech, Inc, Houston, Tex.
Anesthesia and Perioperative Care of the Combat Casualty

238

Black

DBS Twitch

Red

PNS

Tetanus TOF

Path of

ulnar nerve

On–off and

intensity dial

switch

Intensity:

Increases

progressively as the

dial is turned from

setting 1 through 10

Fig. 11-3. Placement of nerve-stimulator electrodes over

the ulnar nerve. Photograph: Courtesy of Organon, Inc,

West Orange, NJ.

Stimulating

electrodes

Medial malleolus

Fig. 11-5. Placement of nerve-stimulator electrodes over

the posterior tibial nerve. Photograph: Courtesy of

Organon, Inc, West Orange, NJ.

Stimulating

electrodes

Fig. 11-4. Placement of nerve-stimulator electrodes over

the facial nerve. Photograph: Courtesy of Organon, Inc,

West Orange, NJ.

employed to assess the diminution of the twitch

response so that the depth of muscle blockade can

be gauged. This type of monitoring is only a crude

measure unless a sophisticated recording device

(eg, a force transducer) can be attached to the patient. Quantifying the loss of twitch height is crucial to assess the blockade accurately. For example,

a 90% suppression of the twitch height is adequate

for endotracheal intubation. Furthermore, 75% to

90% suppression is adequate for surgical relaxation

in the presence of anesthetic agents, while a 25%

suppression is only clinically associated with a decreased vital capacity. Unfortunately, 75% of receptors must be occupied with the neuromuscular blocking before there is a loss of twitch height. Given its

minimal sensitivity, the single-twitch testing method

is not recommended.

Train-of-Four

Four supramaximal stimuli at a frequency of 2

Hz are repeated at intervals longer than 10 seconds

apart. The number of muscle-twitch responses corresponds to the degree of suppression of the initial

twitch response. Loss of the fourth twitch (ie, only

three twitches are seen) corresponds to a 75% suppression of the twitch height, compared to the control. Loss of the third, second, and first twitch

responses corresponds to 80%, 90%, and 100% of the

twitch height, respectively (Table 11-1). Monitoring the TOF is a very useful method of determining

neuromuscular blockade because it does not reSingle Twitch

A single supramaximal stimulus lasting less than

0.2 ms at a frequency of 0.1 Hz is employed to

determine control muscle-contraction response before the neuromuscular blocking agent is administered. Subsequent single-twitch stimuli are then
Neuromuscular Blocking Agents

239

TABLE 11-1

CLINICAL EVALUATION OF NEUROMUSCULAR BLOCKADE

Train-of-Four

Response (Twitches) % Block (Approximate) Clinical Implication of Neuromuscular Blockade

0 > 95 Response indicates clinical overdose of neuromuscular blockade

1 90 Blockade is adequate for intubation

2 80–90 Blockade is adequate for surgery or long-term ventilation

3 75–80 Additional dosing may be required for surgery or long-term

ventilation

3–4 75 Patient is susceptible to reversal of neuromuscular blockade

with anticholinesterase agents

4 ≤ 75 Patient is recovering from neuromuscular blockade

quire a control height. Loss of more than three

twitches signifies good intubating conditions, and

maintenance of one to two twitches during continuous neuromuscular blockade confirms adequate relaxation and preserves the ability to reverse the

neuromuscular blocking agents. Total loss of the

four twitches during incremental-bolus or continuous-infusion therapy signifies excessive blockade.

A return of the TOF twitch response suggests recovery from neuromuscular blockade (Figure 11-6).

Tetanic Stimulation

Tetanic nerve stimulation varies in frequency

from 50 to 200 Hz, with 50 Hz or 100 Hz being more

commonly employed. Tetanic stimulation at 50 Hz

for 5 seconds is clinically useful to estimate peak

muscle tension. Stimulation at this frequency corresponds to what may be seen with maximum voluntary muscular effort. Peak muscle tension in

response to tetanic stimulation is reduced in the

presence of both depolarizing and nondepolarizing

blockade, but fade to tetanic stimulation is only

seen with the latter. This fade to tetanus is a preneuromuscular junction phenomenon. It is due to

curare-like drugs acting on acetylcholine mobilization during high-frequency stimulation. Evidence

of fade with tetanus suggests incomplete recovery

from the neuromuscular blocking agents (Figure

11-7). Fade is termed recurarization if it is seen after

clinical recovery has been determined. Tetanic

stimulation is painful and should only be employed

with this consideration in mind.

Double-Burst Stimulation

Double-burst stimulation is two, short, 50-Hz

tetanic stimuli delivered 750 ms apart. If the response to the second stimulation is less than the

first, then residual curarization can be suspected.

This method is more sensitive in detecting residual

curarization than other methods. As with tetanic

stimulation, double-burst stimulation is also painful to apply.

Clinical Assessment

Although the use of a nerve stimulator is strongly recommended when neuromuscular blocking

agents are being employed, this type of monitor

may be unavailable to the anesthesiologist in the

field setting. The clinician must then gauge the

degree of muscle strength that has returned so that

the casualty’s readiness for extubation can be assessed. The casualty’s ability to sustain a head lift

for 5 seconds, demonstrate a vital capacity of 15 to

20 mL/kg, or generate an inspiratory force of

–25 cm H2O pressure corresponds clinically to

a TOF ratio greater than 0.75 or sustained tetanus

at 50 Hz for 5 seconds. The ability to cough effectively may also indicate adequate respiratory muscle

strength for extubation. Finally, the demonstration of a normal expiratory flow rate, vital capacity,

and inspiratory force greater than 40 cm H2O

pressure can be equated with a TOF ratio of

1.0, indicating full recovery from neuromuscular

blockade.
Anesthesia and Perioperative Care of the Combat Casualty

240

Fig. 11-6. Graphic demonstrations of single-twitch (above) and train-of-four response (below) during onset of and

recovery from nondepolarizing neuromuscular blockade. Reprinted with permission from Shorten G. Neuromuscular

blockade. In: Davison JK, Eckhardt WF III, Perese DA, eds. Clinical Anesthesia Procedures of the Massachusetts General

Hospital. 4th ed. Boston: Mass: Little, Brown; 1993: 167.

min

0

50

100

Percentage Blocade

P T50 Hz

5 s d-TC

SINGLE TWITCH

50

100

25

Percentage of Control Height

0

TRAIN-OF-FOUR

Nondepolarizing

relaxant

TOF count 4 4 32 1 TOF ratio 1 0.25 0.75

Control Height

Fig. 11-7. Loss of response to 0.1 Hz after d-Tubocurarine (left). Decrease in peak muscle tension followed by fade (no

sustained response) after 50-Hz tetanic stimulation (right). Reprinted with permission from Shorten G. Neuromuscular blockade. In: Davison JK, Eckhardt WF III, Perese DA, eds. Clinical Anesthesia Procedures of the Massachusetts General

Hospital. 4th ed. Boston, Mass: Little, Brown; 1993: 158.
Neuromuscular Blocking Agents

241

INDICATIONS FOR NEUROMUSCULAR BLOCKADE

Neuromuscular blocking agents are routinely

used as adjuncts for general anesthesia. Their most

common use is in the facilitation of endotracheal

intubation. For elective surgery, general anesthesia

is typically induced with a hypnotic agent such

as thiopental sodium and a narcotic. Once the

patient is asleep and the ability to ventilate the

patient with a bag-valve-mask system is confirmed,

a muscle relaxant is administered to relax the

jaw, larynx, and diaphragm, and thus to facilitate

smooth endotracheal intubation. Without a neuromuscular blocking agent, a deeper plane of anesthesia is required to achieve the best possible intubating conditions, which may cause significant

hypotension and other detrimental side effects in

some patients.

During the maintenance of general anesthesia,

supplemental doses of neuromuscular blocking

agents are often given to provide optimal operating

conditions for the surgeon. This is especially important in abdominal surgery because the anesthetic agents alone do not provide adequate muscle

relaxation for these procedures unless very high

doses are used.

There is currently great controversy surrounding the use of muscle relaxant agents outside the

operating room, particularly in the intensive care

unit. Muscle relaxation to facilitate endotracheal

intubation by eliminating biting, gagging, combativeness, and laryngospasm is probably the most

common clinical indication for their use outside the

operating room. Caution in using neuromuscular

blocking agents for this purpose must be exercised,

particularly in those patients who may be identified

as difficult to intubate. The need for a possible

surgical airway should be understood, and trained

personnel should be available. Physicians who

prescribe neuromuscular blockade should be trained

experts in airway-management techniques. It is

important to realize that once muscle relaxants are

given, the patient will be totally dependent on controlled ventilation until the drug is eliminated or

antagonized. If the airway cannot be controlled, the

patient will asphyxiate.

Many clinicians contend that there is no role for

these drugs in appropriately sedated patients in the

intensive care unit.3 It is important to stress that

muscle relaxation should never be used without

concomitantly administering sedation in doses adequate to produce amnesia or unconsciousness.

Furthermore, the use of neuromuscular blocking

agents should be limited to the shortest possible

time. Generally accepted clinical applications include those listed in Exhibit 11-1.

Rarely, neuromuscular blockade can aid in

the treatment of medical conditions such as

tetanus, where muscular contraction is itself harmful.4

 Likewise, patients suffering from cardiovascular or metabolic instability due to intractable convulsive activity may transiently benefit from

neuromuscular blockade. Because muscle relaxant

agents do nothing to protect the brain or terminate

intracerebral seizure activity, continuous electroencephalographic monitoring is recommended when

the clinical signs of seizure activity are abolished by

their use.5

The use of a muscle relaxant may occasionally be

a useful adjunct to sedative agents when obtaining

diagnostic procedures or studies.6

 There are rare

patients (eg, those with alcohol withdrawal) whose

combativeness may endanger themselves despite

large amounts of sedative agents. In situations of

this type, muscle relaxants may be necessary temporarily to avoid injury. In addition, these agents

have been used to prevent muscle-activity–induced

increases in intracranial pressure in patients with

head injury.

Neuromuscular blocking agents are useful in

facilitating mechanical ventilation in the intensive

care unit.7,8 Certain modes of mechanical ventilaEXHIBIT 11-1

RATIONALES FOR NEUROMUSCULAR

BLOCKADE IN THE INTENSIVE

CARE UNIT

Facilitate endotracheal intubation

Minimize increased oxygen consumption

associated with muscular activity

Abolish ventilator–patient discoordination

Establish pharmacological restraint

Adjunct to treat septic shock complicated by

acute respiratory failure

Rest fatigued respiratory musculature

Adapted with permission from Hall JB, Schmidt GA,

Wood LDH. Principles of Critical Care. New York, NY:

McGraw Hill; 1992: 976.
Anesthesia and Perioperative Care of the Combat Casualty

242

tion that use prolonged inspiratory times may be

actively opposed by the patient. Allowing permissive hypercapnia and using high levels of positive

end-expiratory pressure may be uncomfortable to

the patient, thus requiring muscle relaxation. Although the use of sedation alone is usually sufficient, some patients demonstrate a respiratory pattern that is discordant with settings chosen for the

mechanical ventilator. The resulting bucking and

straining against the ventilator may provoke pulmonary barotrauma and bronchospasm. Most often, this discordancy signals that ventilator settings

are not suited to the patient’s requirements. Adjustment of the ventilator settings must be considered prior to the institution of muscle-relaxant

therapy.

Theoretically, muscle relaxation can be used to

reduce oxygen consumption in patients with marginal oxygenation. Oxygen consumption by ventilatory muscles is normally 1% to 3% of the available

supply. In acute respiratory distress, the oxygen cost

of breathing can increase to 24% of the supply.9 This

increased oxygen consumption and perfusion of the

stressed respiratory muscles that accompanies the

adult respiratory distress syndrome may potentially

deprive the body of desperately needed energy supplies when oxygen transport is impaired by a reduction in cardiac output, hypoxemia, or anemia.10 Neuromuscular blockade has been shown to improve arterial

oxygenation and decrease oxygen consumption in

patients suffering from respiratory failure, although it

has not yet been shown to improve patient outcome.7,11

TYPES OF MUSCLE RELAXANTS

these, the duration of muscle relaxation is rarely

longer than 20 to 30 minutes.13–15 If it is necessary to

antagonize the prolonged neuromuscular blockade

caused by succinylcholine, then administering fresh

frozen plasma to provide pseudocholinesterase is

effective.16

The administration of succinylcholine has been

associated with many adverse effects. The serum

potassium level is expected to rise from 0.5 to 1.0

mEq/L because potassium leaks from the muscle

cell during depolarization. High serum-potassium

concentrations have been specifically reported after

administration of succinylcholine in patients with

spinal cord transection, nerve damage, burns, major central nervous system injuries, and prolonged

periods of immobility.17,18 The common factor that

appears to link these conditions and the potential

for succinylcholine-induced hyperkalemia is a proliferation of nicotinic cholenergic receptors on

myocytes located away from the neuromuscular

junctions. Such nonjunctional, or extrajunctional,

receptors, when stimulated, remain open 4-fold

longer than normal junctional receptors, a difference that greatly increases the time for potassium

flux.19 It is therefore unwise to administer succinylcholine to such patients after the first 24 hours

from injury, although this effect can be delayed up

to 1 week from injury. Succinylcholine may safely

be administered during the first hours after a traumatic injury. The risk of ventricular fibrillation or

cardiac arrest due to hyperkalemia may persist for

6 months or longer after initial injury in these patients.20 Life-threatening hyperkalemic events can

be treated in the usual fashion with insulin, calcium, and sodium bicarbonate.

Muscle relaxants are classified as depolarizing or

nondepolarizing. The only depolarizing agent in

clinical use in the United States is succinylcholine

chloride. All other muscle relaxants in clinical use

are nondepolarizing in their mechanism of action.

Succinylcholine Chloride

Succinylcholine, consisting of two linked acetylcholine molecules, is a potent acetylcholine agonist

with a rapid onset of action (< 1 min) and brief

duration at clinically used doses (5–10 min). Because of these characteristics, it is an ideal agent in

situations where expedient endotracheal intubation

is required. The intravenous dose used for

intubation is 1 to 1.5 mg/kg in adults and 2 to 2.5

mg/kg in children younger than 2 years of age.12 In

emergency situations where intravenous access is

unavailable, succinylcholine can be administered

intramuscularly in a dose of 4 mg/kg, with a rapid

onset of activity. Great caution should be exercised

when using succinylcholine in children, especially

boys under the age of 8 years. There have been

isolated reports of a succinylcholine-induced

hyperkalemic cardiac arrest in this cohort that may

be related to an undiagnosed muscular dystrophy,

typically of the Duchenne type.

Succinylcholine is rapidly degraded by pseudocholinesterase. Its duration of action may be increased owing to deficiencies in the amount of enzyme (eg, as is seen in patients with liver disease,

pregnancy, cytotoxic agents, and malnutrition).13,14

In addition, genetic abnormalities exist: abnormal

isozymes are estimated to occur in 1 per 3,000 in the

general population.15 Even in situations such as
Neuromuscular Blocking Agents

243

Succinylcholine can cause an increase in intraocular pressure and should therefore be used cautiously in patients who have penetrating injuries of

the globe and some types of glaucoma. Controversy exists as to whether succinylcholine should

be used in patients who may have increased intracranial pressure. After succinylcholine has been

administered, small increases in intracranial pressure have been detected in patients whose pressure

previously was normal.21 On the other hand, the

advantage of using succinylcholine in patients who

require tracheal intubation is that it produces a

rapid and profound neuromuscular blockade, which

attenuates any substantial increase in intracranial

pressure due to coughing or bucking during the

intubation process.

Another potential adverse effect of succinylcholine is the rare malignant hyperthermia syndrome.

This hypermetabolic syndrome manifests with severe metabolic acidosis and carries a high mortality

if not aggressively treated. The key to treatment is

early administration of dantrolene sodium and supportive therapy until the acidosis and its sequelae

resolve. (For a more complete discussion, see Chapter

29, Malignant Hyperthermia: Military Implications.)

Repeated bolus dosing of succinylcholine should

be avoided: it may cause profound bradycardia due

to repeated stimulation of the muscarinic receptors.

Although this drug is available as a continuous

infusion, its use by this method is not recommended.

Long-term administration of succinylcholine with

doses higher than 5 mg/kg alters the character of

the blockade to that of a nondepolarizing muscular

blockade. This is termed a Phase II blockade and

has the clinical and electromyographic characteristics of a nondepolarizing neuromuscular blockade.

Given its many side effects, the clinical trend has

been to avoid the routine use of succinylcholine for

intubation and general anesthesia in elective surgery. However, when rapid control of the airway is

required, succinylcholine remains the drug of choice

for most clinicians.

Nondepolarizing Agents

Nondepolarizing agents act as competitive inhibitors at the motor endplate, preventing acetylcholine from binding at receptor sites and therefore

interrupting neuromuscular transmission. Neuromuscular blockade is the result. Because of their

competitive mechanisms of action, the effects of

these drugs can be antagonized (ie, reversed) with

acetylcholinesterase inhibitors such as neostigmine,

pyridostigmine, or edrophonium. The reversal agent

will also increase acetylcholine at both the nicotinic

and muscarinic cholinergic receptors, with resultant bradycardia and other unpleasant muscarinic

effects. Therefore, anticholinergic drugs such as

atropine or glycopyrrolate should accompany the

use of acetylcholinesterase inhibitors when antagonizing neuromuscular blockade. The nondepolarizing neuromuscular blocking agents and their

characteristics are found in Table 11-2.22 The recommended dosages for the acetylcholinesterase inhibitor drugs and the antimuscarinic agents used

for reversal of nondepolarizing neuromuscular

blockade are found in Table 11-3.

Pancuronium Bromide

Pancuronium is an aminosteroid neuromuscular

blocking agent with a long-acting duration of action. Following a dose of 0.08 to 0.12 mg/kg, administered intravenously, pancuronium will produce adequate relaxation for intubation in 90 to 120

seconds, with a duration of approximately 60 minutes.23 Pancuronium undergoes substantial hepatic

metabolism; however, its metabolites are partially

active and depend on renal excretion.8 Owing to

these metabolites, this drug is a poor choice for

patients with renal failure, and hemodialysis is

ineffective for its elimination.24 Increases in the

half-life of pancuronium also occur with liver failure. Thus, any patient with compromised hepatic

or renal function is at risk for prolonged neuromuscular blockade during pancuronium administration. Pancuronium also demonstrates vagolytic

effects that cause tachycardia.25 Generally, the use

of pancuronium in all settings has decreased in the

last several years as newer nondepolarizing drugs

with fewer side effects, faster onset, and shorter

duration have become available.

Vecuronium Bromide

Vecuronium is the 2-desmethyl analog of

pancuronium. It has an intermediate duration of

action, with an onset of dense neuromuscular blockade in 2 to 3 minutes following a dose of 0.1 mg/kg.

The drug is in large part removed via hepatic metabolism and biliary excretion, and is therefore a

poor choice for patients with liver disease.26

Vecuronium has an active 3-desacetyl metabolite.

Renal clearance accounts for up to 25% of the parent

compound and its metabolite’s excretion. Drug

accumulation may account for prolonged recovery

in patients with renal failure. Vecuronium has no

autonomic or vagal blocking activities, and its use
Anesthesia and Perioperative Care of the Combat Casualty

244

TABLE 11-2

NONDEPOLARIZING NEUROMUSCULAR BLOCKING DRUGS

Intubating Dose 25% Recovery of Control Height Infusion Rate

Drug (mg/kg) (min) (μg/kg/min)

Pancuronium bromide (LA) 0.08–0.12 60–120 0.3–0.8

Vecuronium bromide (IA) 0.1–0.2 45–90 0.8–2.0

Atracurium besylate (IA) 0.5–0.6 30–45 4–12

Mivacurium chloride (SA) 0.2–0.25 15–20 3–15

Rocuronium bromide (SO-IA) 0.6–1.0 45–75 8–12

Pipecuronium bromide (LA) 0.8–0.12 60–120 NA

Doxacurium chloride (LA) 0.05–0.08 90–150 NA

51W89 (atracurium stereoisomer)* 0.15–0.2 40–75 1–2

(Mfg: Burroughs Wellcome,

Research Triangle Park, NJ)

ORG 9487 (steroid based)* 1.5 24 NA

(Mfg: Organon, West Orange, NJ)

*Investigational drug

LA: long acting; IA: intermediate acting; SA: short acting; SO-IA: short onset and intermediate acting; NA: information not available

TABLE 11-3

NEUROMUSCULAR BLOCKADE REVERSAL AGENTS

Neuromuscular Dose Time to Peak Duration of Antimuscarinic Dose

Blocking Agent (mg/kg) Antagonism (min) Antagonism (min) Agent (μg/kg)

Edrophonium 0.5–1.0 1 40–65 Atropine 7–10

Neostigmine 0.03–0.06 7 55–75 Atropine 15–30

Glycopyrrolate 10–15

Pyridostigmine 0.25 10–13 80–130 Atropine 15–20

Glycopyrrolate 10–15

Adapted with permission from Shorten G. Neuromuscular blockade. In: Davison JK, Eckhardt WF III, Perese DA, eds. Clinical

Anesthesia Procedures of the Massachusetts General Hospital. 4th ed. Boston, Mass: Little, Brown; 1993: 163.

lyophilized powder and can be stored without refrigeration.

Atracurium Besylate

Atracurium is an intermediate-acting neuromuscular blocking agent with onset characteristics approximately equal to vecuronium at an equivalent

offers hemodynamic stability.27 In addition, the

absence of histamine release during its administration makes it attractive for use in patients with

reactive airway disease. Its shorter duration of

action makes this drug more titratable than

pancuronium. Vecuronium has one advantage of

considerable military medical importance, which it

shares only with succinylcholine: it is available as a
Neuromuscular Blocking Agents

245

dosage that produces skeletal muscle relaxation in

95% of subjects (ED95). Atracurium has potential

advantages in patients who have hepatic or renal

failure, because it undergoes extensive plasma degradation.28 Additionally, atracurium is metabolized via the Hofmann elimination pathway.

Hofmann elimination29 is the spontaneous degradation of atracurium at physiological pH and temperature into laudanosine and a monoquaternary

acrylate. Since Hofmann degradation does not require complete organ function or enzymes for its

metabolism, there is no significant prolongation of

its action in patients with renal or hepatic dysfunction.30,31 Although the clinical importance of

laudanosine in humans is uncertain, this metabolite

causes seizures when high doses are given to animals.32 However, this association with seizures has

not been demonstrated in humans.

Atracurium has minimal cardiovascular effects

following single- or incremental-dose administration sufficient to cause adequate relaxation for

intubation and surgical procedures. In susceptible

individuals, large-bolus doses of atracurium administered over a short time may induce bronchospasm or hypotension due to histamine release.

Mivacurium Chloride

Mivacurium chloride is the newest benzisoquinolinium nondepolarizing muscle relaxant. Its onset

characteristics are similar to those of atracurium

and vecuronium, but it has a shorter duration of

action. Its short duration, like succinylcholine’s, results from its rapid metabolism by pseudocholinesterases. At clinically used doses, mivacurium releases

significant amounts of histamine, with a resultant

potential for inducing hypotension and bronchospasm.

Like patients who have received succinylcholine, those

with deficient or atypical pseudocholinesterase may

have greatly prolonged neuromuscular blockade.

The primary use of mivacurium is in surgery of

short duration, especially if there is a contraindication for the use of succinylcholine.

Rocuronium Bromide

Rocuronium is the latest muscle relaxant to be

introduced into clinical practice in the United States.

While structurally analogous to vecuronium and

pancuronium, it has much faster onset characteristics.33,34 Given in appropriate doses (3- to 4-fold >

ED95), its profile of clinical onset after administration is comparable to that of succinylcholine.34 Like

vecuronium, rocuronium depends primarily on the

liver for metabolism and is excreted by the biliary

system.35,36 The duration of rocuronium is comparable to that of vecuronium (2- to 4-fold > ED95).34

The onset characteristics of this drug are a major

advance in muscle-relaxant pharmacology, allowing clinicians to perform reliable, rapid endotracheal intubations with excellent intubating conditions in 60 to 90 seconds without succinylcholine.

Like other currently available nondepolarizing

muscle relaxants, rocuronium’s duration of effect is

much longer than succinylcholine’s, which may

limit its use in some situations. However, given

circumstances where a muscle relaxant is indicated

for rapid intubation and succinylcholine is

contraindicated, rocuronium is the best alternative

currently available.

Because all patients requiring emergency

intubation are considered to be at risk for aspiration

of stomach contents during the intubation sequence,

a rapid-sequence intubation with cricoid pressure

is commonly performed. If muscle relaxants are to

be used to facilitate intubation, a fast-acting agent

should be selected so that the trachea can be

intubated promptly and the airway protected.

Succinylcholine is most commonly used in this scenario. The list of contraindications and risks with

the use of succinylcholine should be considered.

Most patients with acute (< 24 h) trauma can safely

be given succinylcholine, and the risks of using this

agent should not be overstated. The most reasonable alternative is rocuronium, which has a similarly fast onset at a dose of 0.9 to 1.2 mg/kg (3- to 4-

fold > ED95) but much longer duration (50–90 min).

Rocuronium should be substituted in the patient

with a normal airway who has trauma (including

burns) greater than 24 hours old, increased intracranial pressure, history of neurologic disease, significantly increased serum potassium (renal failure), penetrating eye injury, or a family history of

malignant hyperthermia. The primary disadvantage of rocuronium at this dosage is the duration of

neuromuscular blockade: 1 hour or longer.

Other Agents

Newer neuromuscular blocking agents currently

available for use in the operating room or the intensive care unit include the long-acting drugs

benzylisoquinoline doxacurium chloride and

aminosteroid pipecuronium bromide. Many other

investigational agents are currently being studied.

These newer agents have minimal cardiovascular

effects, but their usefulness in the clinical setting

remains to be determined.
Anesthesia and Perioperative Care of the Combat Casualty

246

COMPLICATIONS OF NEUROMUSCULAR BLOCKADE

As with all interventions, the use of neuromuscular blocking agents has associated risks and complications. It is important to realize that when a muscle

relaxant is administered, the patient will be unable

to ventilate on his own. Therefore, some method of

ventilation must be supplied externally. Neuromuscular blocking agents should never be administered unless the necessary equipment is available to

supply this need. In a patient who is not already

intubated or who does not have a tracheostomy, at

a minimum there should be a laryngoscope with

different types of blades, endotracheal tubes, suction, an oxygen supply, and a method to deliver

positive-pressure ventilation (eg, bag-valve-mask

system, mechanical ventilator). The possibility of

difficult intubation should be considered. This

cannot be emphasized strongly enough: if the airway is not secured in some manner after the muscle

relaxant is administered, the patient will suffocate.

Once intubated, the most serious risk to the patient is accidental disconnection from the mechanical ventilator. Another risk is that the patient will

fail to cough during tracheal suction, which can

lead to retention of secretions. In addition to these,

an increased risk of pulmonary embolism has been

described.37 Patients under neuromuscular blockade are also prone to develop decubitus ulcers and

nerve-compression syndromes. In addition, owing

to these concerns, the nursing workload increases

appreciably when patients are treated with neuromuscular blocking agents.

Recently, numerous reports38–41 have implicated

muscle relaxants as causing generalized weakness

or myopathy following their long-term administration, with recovery periods lasting as long as 6

months. These reports have implicated the

aminosteroid-based agents primarily, although a

later report42 suggests that any of the neuromuscular blocking agents may be involved. However, it is

not yet clear whether muscle relaxants are the precipitating factor. Other possible contributing factors have been identified, including polyneuropathy

and polymyopathy of critical illness, disuse atrophy, aminoglycoside use, and, in particular, steroid

administration.43–45 Particularly noteworthy are the

numerous reports describing otherwise healthy

patients suffering from asthma who were simultaneously treated with corticosteroids and muscle

relaxants for acute respiratory failure.46,47 Patients

who have muscle weakness or difficulty in weaning

from ventilatory management may need electromyographic or histological studies to delineate their

basic neuromuscular problems. Drug interactions

may affect the degree and duration of neuromuscular blockade. The aminoglycosides can prolong the

action of nondepolarizing agents. The mechanisms

of action include inhibition of presynaptic acetylcholine release and stabilization of postjunctional

membranes.48 Patients on anticonvulsants or

aminophylline may be more resistant to depolarizing agents.49

The soldier on the battlefield where unconventional weapons have been or might be used may

present for anesthesia and surgery after having

been exposed to a variety of agents that impact on

the management of neuromuscular blocking agents

and anesthesia. These agents include not only chemical warfare agents but also pyridostigmine, which

would have been given to the soldiers for nerve

agent prophylaxis, and atropine and cholinesterase

reactivators such as 2-pyridine aldoxime methyl

chloride (2-PAM Cl), with which soldiers are expected to treat themselves immediately after exposure. Medical officers who are performing triage on

chemical casualties who also need surgery may not

be able to ascertain exactly how much nerve agent,

prophylactic agent, and early treatment drugs the

casualty has received. This topic is discussed more

fully in Chapter 30, Anesthesia for Casualties of

Chemical Warfare Agents.

SUMMARY

nately, the use of succinylcholine in certain types of

casualties (eg, those with chronic burns or injuries

to the spinal cord, or who are recovering from

massive injury) has been associated with fatal cardiac dysrhythmias due to hyperkalemia. Succinylcholine should not be used in such casualties, nor in

casualties in whom the initial increase in local muscle

tension caused by depolarization is undesirable.

An example of the latter contraindication is the casuMuscle relaxants have four important adjunctive

roles in the management of combat casualties: (1) to

assist in airway intubation; (2) to optimize operative exposure, especially during laparotomy; (3) to

assure a quiet operating field; and (4) to assure adequate mechanical ventilation to patients in the intensive care ward. Muscle relaxants such as succinylcholine, which depolarizes motor endplates, have a

rapid onset and a short duration of action. Unfortu-
Neuromuscular Blocking Agents

247

alty with a penetrating wound of the eye, in whom

prolapse of the intraocular contents is possible.

Nondepolarizing muscle relaxants block the acetylcholine receptor without causing depolarization.

They typically have a slower onset of action than

does succinylcholine, but their duration of action is

more prolonged. Nondepolarizing neuromuscular

blocking agents may be used when succinylcholine

is contraindicated or when the casualty has impaired cardiovascular function. When quantitative

assessments of neuromuscular function using a

nerve stimulator cannot be made, extubation of a

casualty who has received a muscle relaxant should

be considered only after return of muscle function

is assessed by the patient’s ability to sustain a 5-

second head lift and to generate an inspiratory force

of –25 cm H2O pressure. Some of the newer nondepolarizing muscle relaxants such as atracurium,

vecuronium, and rocuronium are not dependent on

renal metabolism and should be considered safe to

administer to patients in acute renal failure.

The use of neuromuscular blocking agents in

casualties who have been exposed to nerve agents,

and in those who have been given nerve agent

prophylaxis in the form of pyridostigmine, can cause

special treatment problems for military anesthesia

providers. Soldiers who have received pyridostigmine may be especially sensitive to succinylcholine, while simultaneously being relatively refractory to the effects of nondepolarizing agents.

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Anesthesia and Perioperative Care of the Combat Casualty

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16. Epstein HM, Jarzemsky D, Zuckerman L, Vagher P. Plasma cholinesterase activity in the blood bank. Anesth

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20. Sharpe MD. The use of muscle relaxants in the intensive care unit. Can J Anesth. 1992;39:949–962.

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22. Savarese JJ, Miller RD, Lien CA, Caldwell JE. Pharmacology of muscle relaxants and their antagonists. In: Miller

RD, ed. Anesthesia. 4th ed. New York, NY: Churchill Livingstone; 1994: 417–487.

23. Hilgenberg JC. Comparison of the pharmacology of vecuronium and atracurium with that of other currently

available muscle relaxants. Anesth Analg. 1983;62:524–531.

24. Sangala W, Dixon J. Pancuronium and renal failure. Anaesthesia. 1987;42:1236. Letter.

25. Kelman GR, Kennedy BR. Cardiovascular effects of pancuronium in man. Br J Anaesth. 1971;43:335–338.

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pharmacodynamics of vecuronium (ORG NC 45) in patients with cirrhosis. Anesthesiology. 1985; 62:601–605.

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29. Hofmann AW. Beitrages zur Kenntriss der fluchtragen organischen Basen. Ann Chem. 1851;78:253–259.

30. Nigrovic V, Fox JL. Atracurium decay and the formation of laudanosine in humans. Anesthesiology. 1991;74:446–454.

31. Fahey MR, Rupp SM, Fisher DM, et al. The pharmacokinetics and pharmacodynamics of atracurium in patients

with and without renal failure. Anesthesiology. 1984; 61;699–702.

32. Chapple DJ, Miller AA, Ward JB, Wheatley PL. Cardiovascular and neurological effects of laudanosine: Studies

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33. Bowman WC, Rodger IW, Houston J, Marshall RJ, McIndewar I. Structure:action relationships among some

desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat. Anesthesiology. 1988;69:57–62.

34. Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapidsequence induction of anesthesia in adult patients. Anesthesiology. 1993; 79:913–918.

35. Khuenl-Brady K, Castagnoli KP, Canfell PC, Caldwell JE, Agoston S, Miller RD. The neuromuscular blocking

effects and pharmacokinetics of ORG 9426 and ORG 9616 in the cat. Anesthesiology. 1990;72:669–674.

36. Magorian T, Wood P, Caldwell J, et al. The pharmacokinetics and neuromuscular effects of rocuronium bromide

in patients with liver disease. Anesth Analg. 1995;80:754–759.

37. Miller-Jones CM, Williams JH. Sedation for ventilation: A retrospective study of fifty patients. Anaesthesia. 1980;

35:1104–1106.
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38. Gooch JL, Suchyta MR, Balbierz JM, Pentajan JH, Clemmer TP. Prolonged paralysis after treatment with

neuromuscular blocking agents. Crit Care Med. 1991;19:1125–1131.

39. Vanderheyden BA, Reynolds HN, Gerold KB, Emanuele T. Prolonged paralysis after long-term vecuronium

infusion. Crit Care Med. 1992; 20:304–307.

40. Margolis B, Khachikeon M, Friedmen Y, Gorrad C. Prolonged reversible quadriparesis in mechanically

ventilated patients who received long-term infusions of vecuronium. Chest. 1991; 100:877–878.

41. Segredo V, Caldwell JE, Matthay MA, Sharma ML, Gruenke LD, Miller RD. Persistent paralysis in critically ill

patients after long term administration of vecuronium. N Engl J Med. 1992;327:524–528.

42. Manthous CA, Chatila W. Prolonged weakness after the withdrawal of atracurium. Am J Respir Crit Care Med.

1994;150:1441–1443.

43. Zochodne DW, Bolton CF, Wells GA, et al. Critical illness polyneuropathy: A complication of sepsis and

multiple organ failure. Brain. 1987;110:819–841.

44. Danon MJ, Carpenter S. Myopathy with thick filament (myosin) loss following prolonged paralysis with

vecuronium during steroid treatment. Muscle Nerve. 991;14:1131–1139.

45. Vital Brazil O, Prado-Franceschi J. The nature of neuromuscular block produced by neomycin and gentamicin.

Arch Int Pharmacodyn Ther. 1969;179;78–85.

46. Douglass JA, Tuxen DV, Horne M, et al. Myopathy in severe asthma. Am Rev Respir Dis. 1992;146:517–519.

47. Williams TJ, O’Hehir RE, Czarny D, Horne M, Bowes G. Acute myopathy in severe asthma treated with

intracavernously administered corticosteroids. Am Rev Respir Dis. 1988;137:460–463.

48. Sokoll MD, Gergis SD. Antibiotics and neuromuscular function. Anesthesiology. 1981;55:148–159.

49. Doll DC, Rosenberg H. Antagonism of neuromuscular blockage by theophylline. Anesth Analg. 1979;58:139–140.
Regional Anesthesia

251

BEN H. BOEDEKER, D.V.M., M.D., PH.D.*; AND GEORGE W. RUNG, M.D.†

CHAPTER 12

REGIONAL ANESTHESIA

INTRODUCTION

BENEFITS OF NEURAL BLOCKADE

LOCAL ANESTHETICS

Chemical Structures and Physicochemical Properties

Physiology of Neural Blockade

Clinical Use

Properties of Individual Drugs

Adverse Reactions to Local Anesthetics

REGIONAL ANESTHESIA FOR THORACIC AND ABDOMINAL SURGERY

Applied Anatomy for Regional Anesthesia of the Chest and Abdomen

Applied Physiology for Regional Anesthesia of the Chest and Abdomen

Specific Regional Anesthetic Techniques

SPECIFIC NERVE BLOCK TECHNIQUES

Regional Anesthesia of the Head and Neck

Regional Anesthesia of the Airway

Nerve Blocks for Upper Extremity Surgery

Sole-Anesthetic Nerve Blocks for Lower Extremity Surgery

SUMMARY

*Major, Medical Corps, U.S. Army; Assistant Professor, Department of Anesthesiology, Uniformed Services University of the Health Sciences,

Bethesda, Maryland 20814-4799; Assistant Clinical Professor, Pennsylvania State University, College of Medicine, Department of Anesthesia,

Hershey Medical Center, Hershey, Pennsylvania 17033

†Associate Professor and Director, Acute Pain Management Service, Pennsylvania State University, College of Medicine, Department of

Anesthesia, Hershey Medical Center, Hershey, Pennsylvania 17033
Anesthesia and Perioperative Care of the Combat Casualty

252

INTRODUCTION

Regional anesthesia has its greatest use in the

surgical repair of extremity wounds, and during

wartime, extremity wounds occur more frequently

(see Figure 1-6, Chapter 1, Combat Trauma Overview) than any others. A regional anesthetic procedure can be done for (a) almost any isolated wound

that does not cross the midline of the body, and (b)

multiple wounds of a single extremity or both legs.

A craniotomy can be done under local infiltration,

although penetrating head wounds are rarely managed without general anesthesia. Intrathoracic and

intraabdominal pain may be relieved quite well by

regional block, and this technique should be a major

part of preoperative and postoperative management. Surgery in these areas is best accomplished

under general anesthesia owing to the need, in

many cases, for control of the airway and ventilation. Not more than 10%1 of all combat casualties

will arrive in a state of shock at a medical treatment

facility with surgical capabilities, thereby assuming

hypovolemia and a significant risk for major conduction nerve block anesthesia.

Nerve blocks may be useful to provide preoperative analgesia, intraoperative anesthesia as the

sole anesthetic or as a supplement to general anesthesia, or postoperative analgesia. Some nerve

blocks are suited for all three of these uses, while

others provide good analgesia but may not be acceptable for intraoperative anesthesia.

The physiological benefits of regional anesthesia

are numerous (Exhibit 12-1), but the most important

advantage of regional anesthesia is that general anesthesia is avoided, with its associated loss of airway

reflexes, cardiac and respiratory depression, need

for endotracheal intubation and mechanical ventilation, loss of patient cooperation, and residual

anesthetic effects. Regional anesthesia is not without risk; however, nerve blocks are usually less

invasive and affect fewer vital body systems than

general anesthesia (Table 12-1).

EXHIBIT 12-1

PHYSIOLOGICAL BENEFITS OF

REGIONAL ANESTHESIA

Analgesia

Clear sensorium

Deafferentation

Improved respiratory mechanics

Unimpaired ventilatory control

Hemodynamic stability

Improved regional blood flow

Blunted neurohumoral response to injury

Reduced metabolic effects of injury

Reduced urinary retention

Improved bowel function

Improved immune function

Reduced muscle spasm

BENEFITS OF NEURAL BLOCKADE

Any new therapy or new indication for an older

technique must be evaluated in terms of the potential benefits to be gained versus the possible risks.

The risks of these procedures include immediate

and long-term complications arising from (a) needle

and catheter placement, (b) toxicity from the local

anesthetic agent itself, and (c) side effects of neural

blockade (eg, hypotension). The risks associated

with individual blocks are discussed in the sections

describing each technique and the section on local

anesthetic pharmacology.

The quality of analgesia provided by neural blockade is superior to that provided by other forms of

pain relief, because local anesthetics may completely

block the transmission of afferent and efferent nerve

impulses.2 Other forms of analgesia only modify

the perception of pain by various mechanisms in

the central nervous system (CNS) and the periphery. For example, salicylates and other nonsteroidal antiinflammatory drugs (NSAIDs) decrease afferent nerve activity after a noxious stimulus by

desensitizing peripheral pain receptors (ie,

nociceptors) and decreasing local inflammation.3

Inflammatory mediators cause increased blood flow

and capillary permeability (ie, the wheal and flare

reaction) around the point of injury, which leads to

edema and an increased perception of pain (ie,

hyperalgesia).4 Afferent impulses are subject to
Regional Anesthesia

253

TABLE 12-1

REGIONAL VERSUS GENERAL ANESTHESIA

Clinical Criteria Regional General

Sensorium Lucid Unconscious

Patient Positioning Self-assist Dead weight

Airway Reflexes Intact Lost

Respiratory Drive Intact Impaired

Circulatory Effects Sympathectomy Cardiac depression

Medications Administered Few Many

Postoperative Analgesia Yes No

modulation at the level of the spinal cord prior to

transmission to higher centers. One site of modulation by several systems is the dorsal horn of the

spinal cord. Endogenous and exogenous opioids,

α-adrenergic agonists, serotonin, substance P, and

descending inhibitory nerves have been shown5 to

affect neural activity in the dorsal horn. Inhibitory

systems may be stimulated by administering epidural or intrathecal opioids, systemic opioids (increases descending inhibitory impulses), or α-adrenergic agents (clonidine).5 (Also see Chapter 13,

Perioperative Pain Management, and Figure 13-1.)

None of these treatments are as effective as local

anesthetics applied to peripheral nerves or injected

into the epidural or intrathecal space because nerve

impulses are completely blocked by local anesthetics and may provide surgical anesthesia. Studies2,6,7

that compare nerve blocks using local anesthetics to

systemic, epidural, or intrathecal opioids uniformly

reveal that the analgesia provided by neural blockade is superior to that of the other forms.

Owing to their close proximity, somatic neural

blockade with local anesthetics will often also block

sympathetic afferent and efferent nerves. Selective

sympathetic nerve block may also be accomplished,

usually at a paravertebral location, in which a ganglion of the sympathetic chain is blocked. A transient condition equivalent in effect to a sympathectomy by either mechanism has several potentially beneficial effects. Decreased sympathetic

outflow causes vasodilation and increased regional

blood flow to the area innervated, which may

decrease ischemic pain, promote healing, improve

plastic surgical graft survival, and retard vascular

graft thrombosis.8,9 Blockade of sympathetic afferent fibers inhibits segmental spinal reflexes that

may increase pain perception by local secretion

of norepinephrine, substance P, and bradykinin,

which increases nociceptor sensitivity. The vasodilation caused by sympathectomy may also decrease

systemic blood pressure if an adequate intravascular volume is not maintained. A mild decrease

in blood pressure may be desirable because myocardial work is reduced and wide variations in

blood pressure, especially in response to manipulation or movement of the blocked area, may be prevented. Additionally, decreased intraoperative

bleeding and perioperative blood replacement are

reported benefits of neural sympathectomy, probably due to the combination of stable hemodynamics and dilation of venous capacitance vessels.10

Perioperative thromboembolism is also reduced,

not only for the above reasons but also because

patients with effective analgesia tend to ambulate

earlier.11

Modification of the neurohumoral response to

surgery and trauma is the subject of much attention

and effort.12–14 The stress response is a protective

reflex in which acute injury or stress triggers a

tremendous sympathetic discharge, which then results in elevated plasma catecholamines, cortisol,

glucose, antidiuretic hormone, and acute-phase

proteins. These changes produce tachycardia, vasoconstriction, hypertension, increased oxygen consumption, negative nitrogen balance, and salt and

water retention. In 1914, George W. Crile and

William E. Lower coined the term “anoci-association” to describe the physiological changes associated with injury, and correctly predicted that the

changes may be detrimental and retard the healing

process.15 Most efforts to attenuate the surgical

stress response have been directed toward treating

the consequences of the efferent sympathetic activity (eg, tachycardia, hypertension, increased myocardial oxygen consumption, and myocardial

ischemia and infarction).16–18 This practice may be

expected to contribute to improved outcome and

therefore has changed the way many anesthesiolo-
Anesthesia and Perioperative Care of the Combat Casualty

254

gists practice. Neural blockade, however, may

go one step further by blocking somatic and sympathetic afferent activity, which serves to prevent

the neurohumoral response to injury rather than

to treat it after the fact. Outcome data are incomplete, but evidence14 indicates that morbidity and

mortality are reduced in high-risk surgical patients.

Neural blockade improves decreased respiratory

function after trauma or operation.19 Both lung

volumes (ie, functional residual capacity [FRC] and

forced expiratory volume in 1 second [FEV1]) increase, in some cases to near baseline levels.20 This

improvement is greater than that achieved with

intramuscular or epidural opioid analgesia, even if

complete pain relief is obtained.21 The mechanism

of improvement is probably related not only to

inhibition of segmental spinal reflexes that cause

skeletal muscle spasm or splinting but also to superior pain relief. Improved respiratory mechanics

support normal blood gases, pulmonary toilet, and

decreased incidence of atelectasis and infection.

Nerve blocks using higher concentrations of local anesthetics (ie, lidocaine 1.5%–2.0% or bupivacaine 0.5%–0.75%) may produce motor neuron

blockade and skeletal muscle relaxation. Dilute

solutions of local anesthetics may block only sympathetic and sensory nerve fibers, and may spare

motor nerves because of their larger size and greater

myelinization. Skeletal muscle relaxation inhibits

patient movement and ambulation, which may be

distressing to the uninformed patient, but is desirable in certain conditions such as muscle spasm.

The relaxation of muscle spasm by neural blockade

also improves blood flow through the muscle tissue, which may permit metabolic products associated with muscle ischemia to wash out. This may

break the pain–spasm–ischemic pain–continued

spasm cycle and prevent sensitization of sensory

receptors. Immobility of limbs for a short while

after surgery may also prevent disruption of repair

caused by excessive patient movement.

Properly administered neural blockade promotes

a stable hemodynamic profile. Blockade of somatic

and sympathetic afferent fibers attenuate increases

in heart rate, blood pressure, and myocardial work

in response to pain.22–24 Nerve blocks may also

prevent elevation of plasma epinephrine, norepinephrine, antidiuretic hormone, cortisol, and other

chemical mediators, which minimizes secondary

changes in hemodynamic parameters.12 Circulatory changes in response to stimulation such as

patient movement or procedures (eg, changing surgical dressings) may also be minimized. Indirectly,

nerve blocks promote hemodynamic stability by

enabling patients to be extubated soon after surgery

and thus avoid the circulatory changes associated

with prolonged intubation and mechanical ventilation. Although sympathetic blockade may cause

systemic arterial hypotension, this does not usually

occur unless a major conduction block (eg, spinal or

epidural anesthesia) is used and extends to the

midthoracic or higher level of the spine. Systemic

arterial hypotension may be minimized by adequate

intravascular volume loading prior to the block.

Neural blockade may also obviate the need for

other analgesics, sedatives, and anesthetics. Alternative methods of analgesia may provide not only

suboptimal analgesia but also incur the risks of the

alternative therapy. Systemic opioids, for example,

exhibit tremendous variation in interpatient analgesic response, especially when given intramuscularly on an intermittent or as-needed dosage schedule.25 Systemic side effects of opioids include

sedation, depression of ventilatory response to carbon dioxide, nausea, pruritus, and constipation.26

Continuous or on-demand administration of opioids by mechanical patient-controlled analgesia

pumps may minimize side effects. 26,27 The

interpatient variability of opioids administered by

the epidural or intrathecal route is also unpredictable.28 Because a patient’s response to a prescribed

dose of opioid cannot be predicted, opioids should

be administered with caution, regardless of route,

and side effects treated promptly. The use of continued intubation and mechanical ventilation for

analgesia after surgery risks complications caused

by prolonged airway instrumentation and positive

pressure ventilation.

LOCAL ANESTHETICS

Chemical Structures and Physicochemical

Properties

Local anesthetics are chemical compounds that

cause reversible blockade of nerve impulses. Commonly used local anesthetics are tertiary or secondary amines bound to an aromatic ring by either an

amide or an ester chemical linkage. This distinction

divides these drugs into two groups: aminoamides

and aminoesters (Figure 12-1). These compounds

exhibit both lipophilic and hydrophilic properties.

The aromatic ring structure is the lipophilic portion
Regional Anesthesia

255

H

2H5

N

C2H5

C3H7

Prilocaine 220 7.7 0.9 ∼55

Mepivacaine 246 7.6 0.8 77.5 N

H

C

O

H3

H3

N

H

CH3

N

H

C C

H

CH3

N

O

H3

Molecular %

Aromatic Intermediate Amine Weight pKa Partition Protein

Agent Lipophilic Chain Hydrophilic (base) (25°C) Coefficient Binding

H2N

H N

H

Cl

Bupivacaine 288 8.1 27.5 95.6

Lidocaine 234 7.7 2.9 64.3

Chloroprocaine 271 8.7 0.14 —

Procaine 236 8.9 0.02 5.8

C

O

O C

H

H

C

H

H

N

C2H5

C2H5

C4H9 N

H

Esters

N

CH3

CH3

Tetracaine 264 8.6 4.1 75.6

Amides

N

H

CH3

N

H

C C

H

H

O

H3

N

C2H5

C2H5

N

H

CH3

CH3

N

C2H5

N

H

CH3

CH3

N

H

C

O

H3

H3

N

H

CH3

CH3

Etidocaine 276 7.7 141 94

.

N

H

C C

O

CH3

CH3

H

C2H5

N

N

C2H5

C2H5

H3

N

H

C3H7

N

C4H9

C

O

O C

H

H

C

H

H

l

C

O

O C

H

H

C

H

H

of the molecule. The amine structure is the hydrophilic portion. Ionization of the amine portion to a

positively charged species enhances the hydrophilic

properties of the molecule.29

Local anesthetics are weak bases with pKa values

between 7.5 and 9.0. Their physicochemical properties largely determine their clinical anesthetic characteristics. Inherent potency of all anesthetic compounds, including local anesthetics, correlates well

with each compound’s lipid solubility. Chloroprocaine, for example, is poorly soluble in lipid and

has a relatively low anesthetic potency (concentrations of 2%–3% are required for clinical use).

Bupivacaine, on the other hand, is lipid soluble and

has greater anesthetic potency (more dilute solutions, 0.25%–0.5%, are clinically effective). Onset of

Fig. 12-1. Physicochemical properties of local anesthetics. Adapted with permission from Scott DB. Techniques of

Regional Anaesthesia. Norwalk, Conn: Appleton & Lange; 1989: 16.
Anesthesia and Perioperative Care of the Combat Casualty

256

action correlates roughly with a local anesthetic’s

pKa. The pKa of any compound is the pH at which

equal amounts of nonionized and ionized species

exist in equilibrium. The amount of each form at

any given time depends on the local pH. This is

illustrated by the formula

available for participation in neural blockade is

important; therefore, higher concentrations and

larger doses tend to speed onset. The addition of

vasoconstrictors to the local anesthetic solution

decreases the rate of anesthetic uptake by the bloodstream and, in effect, increases the local concentration, which shortens onset time.33 Systemic absorption of epinephrine or phenylephrine used for this

purpose may produce undesirable hemodynamic

changes in the compromised patient. The addition

of bicarbonate to the drug solution increases local

tissue pH, which increases the amount of easily diffusible nonionized drug present and speeds onset.

Carbonation of local anesthetic solutions also speeds

the onset of action because carbon dioxide rapidly

crosses the cell membrane and lowers intracellular

pH. This acidosis favors ionization of intracellular

local anesthetic molecules, which increases the activity of the drug by enhancing receptor binding.

Local anesthetic activity and duration of action

are also enhanced by adding vasoconstrictors to the

solution.29 The anatomical location of the anesthetic

injection affects the onset and duration of the local

anesthetic action because the vascularity of the tissue and the regional blood flow determine the rate

of local anesthetic uptake by the blood.31 The local

anesthetic concentrations in plasma after injection

of a standard dose in different anatomic locations is

shown in Figure 12-2. The highest plasma concentration occurs after injection into the intercostal space.

Tachyphylaxis (ie, the development of a decreased

effect from a given dose of drug after repeated

administration) may be caused by a gradual exhaustion of local tissue-buffering capacity, which

is, in turn, caused by repeated injections of the

relatively acidic local anesthetic salt solutions.

Continuous infusion of anesthetic solution (rather

than intermittent injection) or using a different local anesthetic may decrease tachyphylaxis.

Properties of Individual Drugs

The clinical uses and appropriate doses of commonly used local anesthetics are listed in Table 12-

2. Although local anesthetics share a common

mechanism of action, individual drugs have different indications, side effects, and other properties,

such as addiction potential. Important properties

of individual drugs are noted below.

Bupivacaine has a high affinity for protein (95%

of the drug is bound to protein in plasma) and may

be relatively more cardiotoxic than other local anesthetics, because dissociation from cardiac sodium

channels may be very slow.29 Bupivacaine may

pKa = pH + log (Bh+⁄B)

Generally, the higher the pKa of these compounds,

the greater the ionization at a physiological pH of

7.4, and the slower the onset of neural blockade.30

Duration of anesthetic action is dependent on the

local anesthetic’s affinity for protein. Anesthetics

that are highly protein bound (eg, bupivacaine) in

general have a longer duration of action than those

that are not (eg, procaine).

Physiology of Neural Blockade

Impulses are propagated along nerve cell axons

by progressive depolarization of the cell membrane.

Depolarization occurs when sodium rapidly enters

the cell through sodium channels. Local anesthetics

are thought to physically block, or to induce conformational changes within, these sodium channels by

reversibly binding to receptors on the intracellular

side of the membrane. While the sodium channel is

inactive, nerve impulse conduction cannot occur.31

The nonionized lipophilic form of local anesthetic most easily crosses the myelin sheath and

nerve cell membrane, but it is the ionized hydrophilic form that attaches to the receptor in the cell’s

sodium channel to block nerve impulse conduction.32 This is why a local anesthetic with a high pKa

(the ionized form is predominant at pH 7.4 and

crosses the nerve membranes poorly) generally has

a long onset time.

Local anesthetic duration of action correlates with

the degree of protein binding because the local

anesthetic receptor is thought to be a protein in or

near the sodium channel. Anesthetics with high

affinity for protein will dissociate from the receptor

slowly and therefore the effect will be prolonged.

Once dissociated from the receptor, the drug is

taken up by the bloodstream and metabolized in the

plasma (ester hydrolysis) or the liver (ester hydrolysis and amide microsomal degradation).33

Clinical Use

Onset of local anesthetic activity in vivo is dependent on several factors in addition to the pKa of the

drug and the tissue pH. The number of molecules
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257

Intercostal

Caudal

Epidural

Brachial plexus

Sciatic femoral

Intercostal

Brachial plexus

Intercostal

Caudal

Mepivacaine

500 mg

Lidocaine

400mg

Prilocaine

400 mg

Etidocaine

300 mg

Intercostal

Caudal

Epidural

Epidural

Br. pl.

Subcut.

012 3 4567 8

Epidural

Mepivacaine is not effective when used topically. It is also not desirable for use in obstetric

anesthesia because neonatal metabolism of

mepivacaine is five times slower than in the adult.

Because U.S. military forces are used increasingly

in operations other than war (OOTW, eg, peacekeeping missions), anesthetic procedures used with

obstetric, neonatal, and pediatric patients are assuming greater relevance to military medicine.

Prilocaine may produce methemoglobinemia due

to the accumulation of a metabolite, o-toluidine,

which oxidizes hemoglobin to methemoglobin. This

may occur after high doses of prilocaine, usually

greater than 600 mg, have been administered. If

methemoglobinemia occurs, it can be treated by

administering reducing agents (eg, methylene blue

1 mg/kg).29

Adverse Reactions to Local Anesthetic

True allergy to local anesthetic drugs is extremely

rare. When it occurs, it is usually due to hypersensitivity to a preservative (eg, p-aminobenzoic acid)

or a metabolite of local anesthetics. Most reactions

assumed to be allergic are actually due to

• systemic effects of toxic plasma concentrations of local anesthetic as a result of relative overdosage, or to intravascular injection of an otherwise appropriate dose;

• systemic epinephrine effects;

• a vasovagal reaction; or

• total spinal blockade (ie, high spinal causing cardiopulmonary collapse, which may

mimic anaphylactic shock).

The cause of the adverse reaction must be determined quickly before appropriate treatment can be

instituted.

Toxic plasma concentrations are manifest by CNS

signs: first tinnitus, circumoral numbness, metallic

taste, and then with increasing plasma concentration, tremulousness that may progress to seizure

activity. A very small dose of local anesthetic may

cause CNS signs if injected into an artery that perfuses the brain (eg, the vertebral artery). These CNS

signs may be followed by cardiovascular effects,

which require higher plasma concentrations. Direct depression of myocardial inotropy and

chronotropy occur, in addition to systemic arterial

vasodilation. Cardiac dysrhythmias and cardiovascular collapse may occur secondary to acidosis

and hypoxia caused by seizure activity when local

anesthetic plasma concentration is below cardiotoxic

Blood Levels (μg/mL)

produce sensory blockade without motor blockade

(ie, selective sensory block) at low concentrations.

Chloroprocaine is rapidly metabolized in plasma

by pseudocholinesterases and therefore has a short

duration of action and low toxicity potential. Patients with abnormal or decreased plasma cholinesterase may have a prolonged duration of action.

Use of chloroprocaine may prolong the effect of

other drugs metabolized by cholinesterases (eg,

succinylcholine).

Cocaine is used exclusively for topical anesthesia

of the nose and throat. It causes vasoconstriction,

CNS stimulation, and is highly addictive.30 Addition of a vasoconstrictor is both unnecessary and

undesirable.

Etidocaine and lidocaine are structurally similar

and have similar onsets of action. Etidocaine’s

duration of action is longer than lidocaine’s and the

degree of motor blockade is greater. Lidocaine has

the largest number of clinical uses and may be used

for topical, infiltration, plexus, epidural, and spinal

anesthesia; and intravenous treatment of cardiac

dysrhythmias.

Fig. 12-2. Comparative peak blood levels of several local

anesthetic agents. Reprinted with permission from Covino

BG, Vassallo HG. Local Anesthetics: Mechanism of Action

and Clinical Use. New York, NY: Grune and Stratton;

1976: 97. In: Carpenter RL, Mackey DC. Local anesthetics.

In: Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia. Philadelphia, Pa: JP Lippincott; 1989: 384.
Anesthesia and Perioperative Care of the Combat Casualty

258

TABLE 12-2

COMMONLY USED LOCAL ANESTHETICS: CLINICAL USES AND APPROPRIATE DOSES

Recommended

Usual Maximum pH

Concentration Duration Single Dose of Plain

Agent (%) Clinical Use Onset (h) (mg) Comments Solutions*

Amides

Lidocaine 0.5–1.0 Infiltration Fast 1.0–2.0 300 Most versatile agent. 6.5

0.25–0.5 IV Regional 500 + Epi

1.0–1.5 Periph nerve blocks Fast 1.0–3.0 500 + Epi

1.5–2.0 Epidural Fast 1.0–2.0 500 + Epi

4 Topical Mod 0.5–1.0 500 + Epi

5 Spinal Fast 0.5–1.5 100

Prilocaine 0.5–1.0 Infiltration Fast 1.0–2.0 600 Least toxic amide agent. 4.5

0.25–0.5 IV Regional 600 Methemoglobinemia usually occurs

above 600 mg.

1.5–2.0 Periph nerve blocks Fast 1.5–3.0 600

2.0–3.0 Epidural Fast 1.0–3.0

Mepivacaine 0.5–1.0 Infiltration Fast 1.5–3.0 400 Plain mepivacaine solution has longer 4.5

500 + Epi duration than plain lidocaine solution.

Useful when epinephrine is contraindicated.

1.0–1.5 Periph nerve blocks Fast 2.0–3.0

1.5–2.0 Epidural Fast 1.5–3.0

4.0 Spinal Fast 1.0–1.5 100

Bupivacaine 0.25 Infiltration Fast 2.0–4.0 175 Lower concentrations provide 4.5

225 + Epi differential sensory/motor block.

Ventricular arrhythmias and sudden

cardiovascular collapse reported

following rapid IV injection.

0.25–0.5 Periph nerve blocks Slow 4.0–12.0 225 + Epi

0.25–0.5 Obstetric epidural Mod 2.0–4.0 225 + Epi

0.5–0.75 Surgical epidural Mod 2.0–5.0 225 + Epi

0.5–0.75 Spinal Fast 2.0–4.0 20

Etidocaine 0.5 Infiltration Fast 2.0–4.0 300 Profound motor block useful for surgi- 4.5

400 + Epi cal but not for obstetric analgesia.

0.5–1.0 Peripheral Fast 3.0–12.0 400 + Epi

1.0–1.5 Surgical epidural Fast 2.0–4.0 400 + Epi

Dibucaine 0.25–0.5 Spinal (hyperbaric) Fast 2.0–4.0 10 Recommended only for spinal and ——

topical use.

0.00067 Spinal (hypobaric) Fast 2.0–4.0 10

1.0 Topical Slow 0.5–1.0 50

Esters

Procaine 1.0 Infiltration Fast 0.5–1.0 1,000 Used mainly for infiltration and differ- 5–6.5

ential spinal blocks. Allergic potential

after repeated use.

1.0–2.0 Periph nerve blocks Slow 0.5–1.0 1,000

2.0 Epidural Slow 0.5–1.0 1,000

10.0 Spinal Mod 0.5–1.0 200

Chloroprocaine 1.0 Infiltration Fast 0.5–1.0 800 Lowest systemic toxicity of all local 2.7–4

1,000 + Epi anesthetics.

2.0 Periph nerve block Fast 0.5–1.0 1,000 + Epi Intrathecal injection may be associated ——

with sensory/motor deficits.

2.0–3.0 Epidural Fast 0.5–1.0 1,000 + Epi

Tetracaine 0.5 Spinal Fast 2.0–4.0 20 Use is limited primarily to spinal and 4.5–6.5

topical anesthesia.

2.0 Topical Slow 0.5–1.0 20

Cocaine 4.0–10.0 Topical Slow 0.5–1.0 150 Topical use only. Addictive, causes ——

vasoconstriction. CNS toxicity initially

features marked excitation (fight or

flight response). May cause cardiac

arrhythmias owing to sympathetic

stimulation.

Benzocaine ≤ 20 Topical Slow 0.5–1.0 200 Useful only for topical anesthesia. ——

*Epinephrine-containing solutions have a pH 1 to 1.5 units lower than plain solutions.

Epi: epinephrine; IV: intravenous; Mod: moderate; Periph: peripheral; CNS: central nervous system

Adapted with permission from Covino BG. Clinical pharmacology of local anesthetic agents. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade.

2nd ed. Philadelphia, Pa: JB Lippincott; 1988: 112–113.
Regional Anesthesia

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levels. In general, treatment for toxic local anesthetic reactions is supportive until the drug is redistributed or metabolized, and the tissue levels decrease. The injection of local anesthetic should

cease immediately, the airway be supported, and

supplemental oxygen be administered. Tracheal

intubation and pharmacological treatment of seizures is rarely required.

Intravascular absorption of epinephrine may

cause tachycardia, hypertension, hypotension (a βadrenergic effect), anxiety, restlessness, and a feeling of impending doom. These effects are often

mistaken for local anesthetic toxicity. Treatment is

supportive.

A vasovagal reaction may occur during needle

placement or with injection of local anesthetic.

Bradycardia, hypotension, sweating, and pallor

precede fainting. Administration of atropine intravenously or intramuscularly and supportive measures are indicated.

True allergies to local anesthetics have been reported in a very small percentage of patients. These

reactions are almost always due to hypersensitivity

to the p-aminobenzoic acid metabolic derivatives

of ester-type anesthetic drugs. Allergic reactions

to amide-type drugs are extremely rare. Hypersensitivity to preservatives (eg, methylparaben)

may also occur. Allergic reaction symptoms include urticaria and cutaneous flushing, wheezing, tachycardia, arterial hypotension, and cardiovascular collapse. Treatment consists of maintenance of a patent airway, ventilation with 100%

oxygen, and administration of epinephrine that is

titrated to maintain a normal blood pressure. Steroids and histamine blocking drugs may also be

given.

REGIONAL ANESTHESIA FOR THORACIC AND ABDOMINAL SURGERY

Regional anesthesia for thoracic and abdominal

surgery—except for superficial or lower-abdominal procedures—is usually used in combination

with general anesthesia. Why should patients receive regional anesthesia if they are going to have a

general anesthetic anyway? There are numerous

advantages and disadvantages, and numerous and

varied outcome studies have been performed. The

advantages of combined general–regional anesthesia versus general anesthesia alone include the following:

• The general anesthetic requirement may be

reduced, which may result in a reduction in

dose-related general anesthetic effects, a

faster emergence, earlier extubation, and

shorter hospital stay.14,34

• The combined technique produces a

smoother intraoperative course with more

stable hemodynamic parameters and fewer

changes of anesthetic depth required.35,36

• Noxious afferent input to the spinal cord

may be minimized, which may reduce spinal cord sensitization, thereby decreasing

or causing the development of permanent

spinal cord sensitization, which may give

rise to a chronic pain pathway. Thus the

neurohumoral response to tissue injury is

attenuated.12

• Postoperative analgesia may be provided

by extending the nerve block technique after discontinuing general anesthesia.34,35

• The blockade of sympathetic nerve impulses

to and from the spinal cord may be used to

produce deliberate and controlled hypotension (to reduce bleeding) and may also

provide analgesia for sympathetically mediated pain.37

The disadvantages of combined general–regional

anesthesia versus general anesthesia alone include

the following:

• The additional invasive procedure adds to

the risk of anesthetic complications.38

• The nerve block procedure requires additional anesthetic preparation time. This is

especially disadvantageous if the procedures are done in the operating room.

• The combination of major conduction nerve

blocks and general anesthetic–induced

myocardial depression may result in severe hypotension.14,34

• Some evidence34 indicates that the combination of general and regional anesthesia

is associated with a greater degree of

intraoperative hypothermia than either

technique used alone.

• There is a theoretical increased risk of

intraoperative awareness if low concentrations of inhaled anesthetic agents are used.

Many outcome studies identify positive physiological effects of regional versus general anesthe-
Anesthesia and Perioperative Care of the Combat Casualty

260

sia, including reduced intraoperative blood loss,

improved postoperative respiratory function, maintenance of bowel motility, and more normal metabolic, immune, and hemostatic functions.14,34,39,40

However, very few studies investigate whether these

physiological changes (a) are clinically important or

(b) affect patient outcome. Moreover, studies comparing the outcome of patients who undergo combination general–regional anesthesia versus general anesthesia only are fewer still.14,36 Comparative

studies have been hindered by a relative underutilization of local anesthetics in favor of opioids,

inappropriate epidural catheter placement (eg, lumbar placement for thoracic or upper-abdominal surgery), and administration of lipophilic opioids at a

spinal level (lumbar) distant from the site of action

(thoracic).

Applied Anatomy for Regional Anesthesia of

the Chest and Abdomen

Somatic Nerves

The chest and abdominal wall are innervated by

branches of thoracic spinal nerves. Surgical procedures of the chest and abdomen involve almost

exclusively areas innervated by nine pairs of spinal

nerves, T-4 through T-12. T-1 is part of the brachial

plexus, T-2 and T-3 innervate the chest wall above

the level of the nipples, where thoracic surgery is

rarely performed, and the lumbar spinal nerves

involve only the peripheral (inguinal) lower abdomen. Each spinal nerve has a small dorsal ramus

that innervates paraspinal muscles and skin, and a

large ventral ramus that becomes the intercostal

nerve and innervates skin, muscle, and bone in the

distribution of the corresponding rib.41

Sympathetic and Parasympathetic Nerves

Sympathetic nerves to and from the chest and

abdomen synapse in or pass through the paired

sympathetic chain ganglia located anterior and lateral to the vertebral bodies from T-1 to L-5. Sympathetic outflow from the spinal cord reaches the

sympathetic chain via the white rami communicantes; sympathetic afferents from the chain travel

via the gray rami communicantes to the spinal cord.

The greater, lesser, and least splanchnic nerves are

formed by fibers from the sympathetic chain and

synapse in the mesenteric ganglia.41

Afferent and efferent parasympathetic innervation of the chest and abdomen is largely via the

paired vagal nerves.41

Applied Physiology for Regional Anesthesia of

the Chest and Abdomen

Respiratory Effects

Control of ventilation is not inhibited by regional

anesthesia.42 Some evidence43 suggests that systemic local anesthetics actually increase the ventilatory response to carbon dioxide.

The mechanics of ventilation are often disturbed

after thoracic and abdominal surgery owing to decreased chest-wall compliance and diaphragm dysfunction.34 Regional anesthesia does not affect motor nerves to the diaphragm (eg, the phrenic nerve,

the most important contribution to which is from C4), may rarely weaken some intercostal muscles,

and has been shown to reduce diaphragm dysfunction after upper abdominal surgery.39

Increased airway resistance secondary to reduced

sympathetic efferent activity to the lungs is a theoretical concern, although it has not been reported as

a problem in patients with pulmonary disease who

are undergoing thoracotomy. In fact, thoracic epidural anesthesia has been used to treat status

asthmaticus, presumably by blocking sympathetic

afferent fibers from the airways.21

Circulatory Effects

Cardiac Effects. Bradycardia, junctional rhythm,

or heart block may be caused by blocking of sympathetic nerves to the heart, although complete blockade may be necessary for these effects.15 Coronary

artery blood flow, in normal and stenotic vessels,

and cardiac function may increase dramatically

owing to the sympathetic nerve block associated

with thoracic epidural anesthesia.44,45

Systemic and Pulmonary Artery Blood Pressure.

A decrease in systemic blood pressure is often associated with thoracolumbar sympathetic nerve block,

largely due to dilation of venous capacitance vessels

and decreased venous return to the heart.44 Systemic

vascular resistance is also reduced and cardiac output

may increase if preload is maintained.44 The degree of

hypotension is dependent on the number of spinal

segments blocked. Local anesthetics administered

through a thoracic epidural catheter may cause less

hypotension than a lumbar epidural catheter because some sympathetic outflow may be spared,

innervation of the adrenal glands may be intact, and

the pumping action of the lower extremity muscles

to augment venous return may be functional.

A decrease in pulmonary artery pressure may be

associated with blockade of sympathetic nerves to
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261

the chest unless pulmonary hypertension is caused

by a mechanical resistance (ie, vascular changes or

mitral valvular stenosis).44 In this situation, the

increased impedance offered is not affected by sympathetic blockade.

Endocrine, Gastrointestinal, and Urinary Effects

There is currently no better way to inhibit the

neurohumoral response to tissue injury than via

afferent neural blockade. This benefit may not be

completely realized in thoracoabdominal surgery,

however, because complete afferent blockade is not

commonly attained owing to vagal afferents and

humeral mediators such as cytokines.12

The sympathetic nerve block that may accompany regional anesthesia promotes gastrointestinal

function by creating a predominant parasympathetic nerve influence on the gut, which increases

peristalsis and gut motility.40 This beneficial effect

of regional anesthesia is often augmented by a reduced opioid requirement for adequate analgesia,

and therefore, fewer opioid-induced side effects.

These effects may combine to reduce the incidence

of postoperative ileus.34,35

Urinary retention after surgery may be caused by

residual general anesthetic effect, opioids, neural

blockade, and other drugs. Like gut function, the

ability to void may be maintained by segmental

(thoracic) nerve blockade and the avoidance of

opioid analgesics.34,35

Locomotion

Patients who have received regional anesthesia

for thoracic and abdominal surgery should be able

to ambulate earlier than patients who did not receive regional anesthesia. Motor nerves to the lower

extremity originate in lumbar and sacral spinal

nerves, which may be spared by segmental thoracic

spinal nerve block. The superior analgesia provided by regional anesthesia, without the sedation

caused by systemic analgesics, also promotes early

ambulation.34,35

Specific Regional Anesthetic Techniques

The intelligent use of regional anesthesia for thoracic and abdominal surgery requires that the anesthesiologist have a thorough knowledge of (a) the

anatomy and physiology related to neural blockade, (b) the patient’s medical and surgical history,

and (c) the planned surgical procedure. Techniques

that may be useful for thoracic and abdominal surgery include thoracic epidural anesthesia, spinal

anesthesia, intercostal nerve block, interpleural

nerve block, and incisional local anesthetic infiltration. At least one of these techniques is usually

indicated, regardless of the patient’s condition or

the surgical procedure planned. Characteristics of

each technique are summarized in Table 12-3. Complications of regional anesthesia are discussed later

in this chapter.

TABLE 12-3

REGIONAL ANESTHETIC TECHNIQUES FOR THORACIC AND ABDOMINAL SURGERY

Somatic Sensory Sympathetic Lower Extremity

Technique Nerve Block Nerve Block Motor Block

Epidural Anesthesia

Thoracic + + –

Lumbar + + +

Spinal Anesthesia + + +

Intercostal Nerve Block*

Single + – –

Continuous + –/+ –

Interpleural Nerve Block* + –/+ –

Paravertebral Nerve Block* + –/+ –

Peripheral Nerve Block + – –

*Unilateral anesthesia: (+) = effect; (–) = no effect
Anesthesia and Perioperative Care of the Combat Casualty

262

Epidural Anesthesia

Epidural anesthesia is the most versatile regional

anesthetic technique available in terms of surgical

application, control of extent and duration of nerve

block, and use for postoperative analgesia. Epidural anesthesia can produce segmental sympathetic,

sensory, and motor block for many intrathoracic or

intraabdominal procedures, lower extremity or abdominal surgery, analgesia during labor and delivery, and treatment of medical conditions such as

Raynaud’s phenomenon or postherpetic neuralgia.

Despite the advantages, thoracic epidural anesthesia should not be attempted by anesthesiologists

who are unfamiliar with the technique. As an

alternative, lumbar epidural anesthesia may be used

for thoracic and abdominal surgery if local anesthetics are used intraoperatively to provide an adequate level of anesthesia but are discontinued

postoperatively. Because high volumes of local

anesthetic are required, the sympathectomy may

be extensive, and motor block of the lower extremities will result. Epidural opioids may be used

subsequently to provide postoperative analgesia

without motor block, but this adds the potential for

opioid side effects.

Owing to the close proximity of the underlying

spinal cord, thoracic epidural anesthesia should not

be routinely performed in anesthetized patients.

As with any regional anesthetic technique, if needle

insertion is difficult, multiple attempts should not

be pursued because the incidence of complications

increases inordinately. Know when to abandon the

procedure and use an alternative technique.

Epidural anesthesia is contraindicated in the presence of informed patient refusal, local or severe

systemic infection, abnormal coagulation, unstable

neurological deficits, uncorrected hypovolemia, and

possibly immunosuppression.

Technique. Epidural anesthesia may be performed at any level of the spine. The epidural space

is identified by a characteristic loss of resistance to

depression of the syringe plunger on entering the

space (ie, loss of resistancetechnique) or by the disappearance of a drop of sterile saline from the needle

hub on entering the space owing to the subatmospheric pressure of the space (ie, hanging drop technique). A single-shot technique may be used, in

which one dose of anesthetic is injected into the

space, or a continuous (usually intermittent injection) technique may be used, in which a catheter is

threaded into the space through the needle; then the

needle is removed. In the lumbar spine, a local

anesthetic volume of approximately 1.5 to 2.0 mL

per spinal segment is required for anesthesia. Epidural catheters may be kept in place for 48 to 72

hours or longer if the benefits of analgesia outweigh

the risk of infection.

If local anesthetics will be used postoperatively,

the tip of the epidural catheter should be placed as

closely as possible to the midpoint of the range of

spinal (thoracic) segments to be blocked. This location allows the use of lower volumes of local anesthetics, minimizes the extent of sympathetic nerve

block, and is unlikely to cause lower-extremity motor

block. Suggested levels of epidural catheter placement for given surgical procedures are listed in

Table 12-4.

Local Anesthetic Drug Dosages. Local anesthetics must come into contact with the target nerves to

exert their effect. Epidural dosing of local anesthetics is, therefore, largely based on volume. In the

epidural space, local anesthetics spread in all directions from the catheter tip, but preferentially along

lines of least resistance. The epidural space is smaller

in the thoracic than in the lumbar spine, and the

volume of anesthetic must be adjusted accordingly.

General rules of thumb for adults are given in Table

12-5. The concentration of local anesthetic affects

the speed of onset of block, degree of motor block,

and duration of block. Motor-blocking strengths

may be used intraoperatively, but the lowest conTABLE 12-4

LOCATION OF EPIDURAL CATHETER INSERTION

Site of Surgery Epidural Catheter Dose of Local Anesthetic (mL)

Thoracic Upper thoracic spine (T-4 –T-7) 4–6

Upper abdominal Mid thoracic spine (T-8–T-9) 6–8

Lower abdominal Lower thoracic spine (T-10–T-11) 8–10
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263

Drug Initial Dose (mg) Injectate Volume* (mL) Infusion Rate (mg/h)

TABLE 12-5

EPIDURAL LOCAL ANESTHETIC DOSAGE GUIDELINES

Volume Required Volume Required

Position of Catheter Tip per Spinal Segment (mL) for T-4 Level (mL)

Upper thoracic (T-4–T-7) 1.0 1–6

Mid thoracic (T-8–T-9) 1.5 8–10

Lower thoracic (T-10–T-12) 1.75 12–18

Lumbar (L-1–L-5) 2.0 20–28

centration that provides pain relief should be used

postoperatively.

Opioid analgesics are usually administered on a

milligram-per-kilogram basis. Lipophilic drugs,

such as fentanyl, act via a spinal mechanism if

placed in the thoracic epidural space, and via systemic absorption if placed in the lumbar epidural

space.46,47 Hydrophilic drugs, such as morphine or

hydromorphone, spread more readily through the

epidural space before absorption, act via a spinal

mechanism, and are effective in the lumbar or thoracic epidural space.48,49 Increased respiratory surveillance may be considered if a hydrophilic opioid

is used in the upper-thoracic epidural space. Opioid

dosage guidelines are given in Table 12-6.

Complications. The complications of epidural

anesthesia are similar to those associated with spinal anesthesia (Table 12-7). Possible trauma caused

by needle insertion may be greater owing to the

larger needle size, and the risk of local anesthetic

toxicity is greater owing to the larger doses used.

Inadvertent dural puncture carries a high likelihood of post–dural-puncture headache. A “total”

spinal (ie, the entire spinal cord has been blocked, at

TABLE 12-6

EPIDURAL OPIOID DOSAGE GUIDELINES FOR A HEALTHY, 70-KG, ADULT PATIENT

Morphine 3–5 10 0.2–0.3

Hydromorphone 0.5–1.0 10 60–150

Fentanyl 75–150 10 30–100

Sufentanil 25–50 10 5–15

*Prepare opioid dose in preservative-free saline

least to some extent) may result from intrathecal

injection of a local anesthetic dose appropriate for

epidural administration. As with spinal anesthesia,

sympathetic nerve block may cause systemic

hypotension, especially if the patient is hypovolemic.

Bradycardia may occur if high thoracic spinal levels

are blocked (ie, if cardioaccelerator fibers are anesthetized). Subarachnoid and epidural abscesses

have been reported41 after epidural needle or catheter insertion.

Spinal Anesthesia

Spinal anesthesia has many advantages compared

to epidural anesthesia: much smaller local anesthetic doses are required, systemic vascular absorption and risk of systemic toxicity are negligible,

onset of block is much faster, and the resultant

nerve block is more complete, including motor blockade. Disadvantages include the inability to produce a segmental band of anesthesia, a more extensive virtual sympathectomy with more pronounced

blood pressure changes, and fewer postoperative

analgesic options.50
Anesthesia and Perioperative Care of the Combat Casualty

264

TABLE 12-7

SPINAL VERSUS EPIDURAL ANESTHESIA

Characteristic Spinal Epidural

Onset Fast Slow

Local anesthetic dose Small Large

Local anesthetic plasma Nil Nil

concentration

Density of block Very dense Less dense

(spotty)

Need for supplementation Less likely More likely

Indication of needle Reliable* Less reliable†

placement

Post–dural-puncture Low risk Possible

headache

Hypotension More likely Less likely

Continuous technique Less Very

common common

Postoperative analgesia Possible Common

(Duramorph‡)

*By cerebrospinal fluid

†By loss of resistance

‡Morphine; manufactured by Elkins-Sinn, Cherry Hill, NJ

Spinal anesthesia may be used alone for many

lower-abdominal procedures or lower-extremity

surgery and may be combined with general anesthesia for upper-abdominal surgery. Spinal anesthesia is rarely used for thoracic surgery.

Spinal anesthesia is contraindicated for patients

with coagulation abnormalities, infection at the site

of needle placement, severe systemic infection, uncorrected hypovolemia, unstable neurological deficits, and possibly immunosuppression.

Technique. The basic technique for lumbar puncture may be found in any standard anesthesiology

textbook. The injection of a single dose of local

anesthetic through the spinal needle, a single-shot

technique, is sufficient for many surgical techniques.

The sensory and motor blockade produced by such

a technique depends largely on the local anesthetic

dosage, baricity, and location and speed of injection. Isobaric solutions (bupivacaine 0.5%, lidocaine

2%, and tetracaine 1%) are gaining popularity because neural blockade is independent of patient

position, fewer spinal segments are blocked, and

there are smaller reductions in systemic blood pressure. A continuous catheter technique may be used

(a) to produce a slow onset of neural blockade by

fractionating the total anesthetic dose and (b) to

prolong neural blockade for long surgical procedures. Isobaric local anesthetic solutions are also

useful in continuous catheter techniques because

there is no tendency for the local anesthetic to accumulate in dependent portions of the subarachnoid

space and thus potential neural toxicity (cauda

equina syndrome) may be avoided.

The use of spinal catheters has diminished after

reports of associated cauda equina syndrome.51,52

The mechanism is thought to be related to uneven

distribution of hyperbaric local anesthetic solutions

in the spinal fluid and high (toxic) concentrations

near the sacral nerve roots. To minimize the risk of

neurological injury, spinal catheters should be inserted no more than 2 cm into the subarachnoid

space, recommended maximum local anesthetic

dosages should not be exceeded, and use of isobaric

solutions should be considered.

Complications. The most common complication

associated with spinal anesthesia is hypotension,

which may be controlled by adequate fluid

prehydration and the use of vasopressors. Nausea

and vomiting may be minimized by good blood

pressure control and small doses of antiemetics.

Post–dural-puncture headache (also called spinal

headache) may occur after any dural puncture (eg,

for spinal tap, myelogram, spinal anesthesia) and

may be minimized by using small-gauge, noncutting

needles. Transient and persistent neurological deficits may rarely occur. Spinal hematoma or abscess

are extremely rare but possible complications of

spinal anesthesia.

Practical Points. Injection of hyperbaric local

anesthetic solutions into the L-2–L-3 or L-3–L-4

interspace usually results in a T-4 level block, owing

to the slope of the spinal curvature from the lumbar

lordosis to thoracic kyphosis. Injection into the L-4–

L-5 or L-5–S-1 interspace may result in a somewhat

lower spinal level, owing to collection of some of the

local anesthetic in the sacral spinal space.53

Isobaric local anesthetic solutions (eg, lidocaine

2%, tetracaine 1%, bupivacaine 0.5%) may result in

a lower “highest” level, a smaller range of highest

levels, and smaller blood pressure changes, compared to hyperbaric solutions.53 The resultant spinal level of anesthesia is independent of patient

position at the time of injection. Relatively large

doses may be required to attain a high thoracic

level.

Postoperative analgesia may be provided by

longer acting opioids (eg, morphine 6–20 h) without

causing motor block, but additional respiratory

monitoring may be required postoperatively.54,55

Spinal anesthesia or analgesia should not be used

if local anesthetic block or prolonged analgesia

(> 24 h) is required postoperatively. A continuous
Regional Anesthesia

265

epidural or intercostal catheter technique may be

more appropriate in this setting.

Intercostal Nerve Block

Intercostal nerve blocks may provide better postoperative analgesia than conventional opioid

therapy. When the chest is open, the intercostal

nerves can be injected under direct vision. Intercostal block has no effect on visceral structures, so by

itself it is inadequate for surgery.

Intercostal nerve block should not be used in the

presence of local or severe systemic infection, coagulation abnormality, severe pulmonary disease,

or obesity or other physical condition that may

make rib palpation difficult.

Anatomy. There are 12 pairs of thoracic anterior primary rami: the upper 11 comprise the intercostal nerves and the 12th is termed the subcostal

nerve.56 The 3rd through 11th pairs are responsible

for the innervation of the muscles of the intercostal

spaces and of the anterior abdominal wall, and for

the cutaneous supply of the skin of the medial

aspect of the upper arm and of the anterior and

lateral aspects of the trunk from the level of the

angle of Louis to just above the groin. The 1st, 2nd,

and 12th pairs differ from the others and must be

considered separately when intercostal nerve block

is desired:

• The 1st intercostal nerve sends a large contribution, which passes across the front of

the neck of the first rub, lateral to the superior intercostal artery, to enter the composition of the brachial plexus.

• The 2nd intercostal nerve differs from the

typical intercostal nerves in that its lateral

cutaneous branch crosses the axilla to supply the skin over the medial aspect of the

upper arm. This branch is called the

intercostobrachial nerve.

• The 12th thoracic nerve runs along the lower border of the 12th rib below the subcostal vessels, passes behind the lateral

arcuate ligament to run in front of quadratus lumborum behind the kidney and

colon.56

A typical intercostal nerve has four significant

branches. The first branch is the gray ramus

communicans, which passes anteriorly to the sympathetic ganglion. The second branch arises as the

posterior cutaneous branch. This nerve supplies

skin and muscles in the paravertebral region. The

third branch is the lateral cutaneous division, which

arises just anterior to the midaxillary line. This

branch sends subcutaneous fibers posteriorly and

anteriorly to supply skin of much of the chest and

abdominal wall. The fourth and terminal branch of

an intercostal nerve is the anterior cutaneous

branch,41 which innervates the ventral side of the

chest and the abdominal wall.

Each nerve is joined to its corresponding thoracic

sympathetic ganglion by a white and grey ramus

communicans.56 Distal to the rami communicantes,

the nerve trunk divides into the dorsal and the

ventral branches. The dorsal branch supplies the

skin of the back, the muscles of the back, and the

periosteum of the vertebrae through its lateral and

medial branches.57

The ventral branch follows the rib into the costal

sulcus, into the dorsal thoracic region and between

the two laminae of the intercostal muscles in the

intercostal space, and into the lateral and ventral

portions of the thorax. The ventral branches each

give off a lateral cutaneous branch, first to fifth in

the posterior axillary line and sixth to twelfth in the

anterior axillary line.57

The lateral cutaneous branches of intercostal

nerves 7 through 12 participate in sensory and motor innervation of the anterior abdominal wall (skin,

muscles, parietal peritoneum).57

At the angle of the rib (6–8 cm from the spinous

processes), the nerve comes to lie between the internal intercostal muscle and the intercostalis intimus

muscle. The costal groove is broadest and deepest

at this point. The nerve is accompanied by an

intercostal vein and artery, which lie superior to the

nerve in the inferior groove of each rib. The costal

groove forms a sharp angle with the rib. At this

point, the intercostal groove ceases to exist, the

lateral cutaneous branch is given off, and the intercostal nerve lies more inferiorly and moves toward

the center of the intercostal space.41

Technique. The intercostal nerve block may be

performed at several possible sites along the course

of the nerve, using the following equipment:

• short, beveled, 23- or 25-gauge needle, and

• 10-mL syringe.

The most common site is in the region of the

angle of the ribs just lateral to the sacrospinalis

group of muscles (Figure 12-3).41

Skin markings can be made at the lateral edge of

the sacrospinalis muscle (6–8 cm from the midline).

The line may be curved medially and superiorly to

avoid the scapulae. Skin at the lower edge of the rib
Anesthesia and Perioperative Care of the Combat Casualty

266

Fig. 12-3. Technique for intercostal block. (a) A skin marking

pen is used to mark the individual ribs 6–8 cm from midline,

with the more cranially selected sites being closer to midline.

(b) Skin at the lower edge of the rib is retracted superiorly onto

the rib. (c) The needle is inserted onto the rib. (d) The needle is

walked off the inferior edge of the rib and advanced 3 mm. The

left hand is left firmly against the patient’s back to control the

needle. (e) The anesthetic agent is injected. Reprinted with

permission from Thompson GE, Moore DC. Celiac plexus, intercostal, and minor peripheral blockade. In: Cousins MJ,

Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and

Management of Pain. 2nd ed. Philadelphia, Pa: JB Lippincott;

1988: 513.

is retracted superiorly onto the rib. The needle is

inserted onto the rib then walked off the inferior

edge and advanced 3 mm toward the sulcus of the

rib.41 Aspirate before injecting 3 to 5 mL per segment.41,57 The patient should hold his breath during

the injection.

Local Anesthetic Drug Dosage. Any local anesthetic used for peripheral nerve blocks may be used,

such as 0.5% bupivacaine or 1% etidocaine, in the

amount of 3 to 5 mL.57

Complications. Pneumothorax is the most feared

complication.41 Blood levels of anesthetic agent are

a

b c

d e
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267

higher after this block because of the proximity to

vessels, which can lead to toxic concentrations of

local anesthetics if the patient receives an overdose

of drug. Hemothorax could occur if the intercostal

vessels are damaged.

Practical Points. A catheter technique has many

advantages compared to multiple single injections:

a one-time-only risk of pneumothorax, the ability to

provide prolonged continuous analgesia, and blockade of sympathetic nerve fibers.58,59

Since large volumes (20–30 mL/h) of local anesthetic solutions may be required, use of a drug with

low toxicity potential should be considered. We

have used 1% chloroprocaine with success, although

tachyphylaxis may develop.

Interpleural Nerve Block

Injection of local anesthetics between the visceral

and parietal pleurae provides somatic nerve block by

diffusion to the intercostal nerves, and sympathetic

nerve block by spread to the paravertebral area.60,61

Interpleural nerve block may be used for unilateral

anesthesia of the upper abdomen. This approach to

surgical anesthesia is less useful for thoracic procedures, especially if the pleurae have been disrupted

or if thoracostomy drainage tubes are used.62,63

The effects of interpleural nerve block are similar

to those of continuous intercostal nerve block.64

Compared with continuous intercostal nerve block,

interpleural block is patient-position dependent,

has a higher incidence of pneumothorax, requires a

higher local anesthetic dose, and results in higher

plasma concentration of local anesthetics.65–67 These

characteristics favor use of continuous intercostal

nerve block for unilateral procedures of the upper

abdomen and flank.

Interpleural nerve block should not be used in

the presence of local or severe systemic infection,

coagulation abnormality, severe pulmonary disease, or pleural abnormality.

Peripheral Nerve Blocks

Peripheral nerve blocks and incisional infiltration with local anesthetics provide local somatic

anesthesia. These anesthetic techniques may

be used as the sole anesthesia for extremely limited procedures, to supplement general anesthesia, or to provide several hours of postoperative

analgesia.

Infiltration of the surgical wound with a local

anesthetic drug is an extremely under-utilized technique. It does not require technical expertise, is

safe, and can provide a “bridge” of analgesia between general anesthesia and postoperative analgesia.68 Some evidence suggests that infiltration of

the surgical site prior to incision provides preemptive analgesia (ie, it prevents spinal cord activation

and hyperalgesia by blocking afferent nerves from

the site of injury).69

Peripheral or infiltration blocks are contra-indicated in the presence of local infection or allergy to

the local anesthetic.

SPECIFIC NERVE BLOCK TECHNIQUES

Regional anesthesia provides operative anesthesia and postoperative analgesia for selected casualties receiving surgery during wartime. Use of

regional anesthesia in this casualty population

may prevent some sequelae of general anesthesia

(eg, nausea and vomiting) and should decrease

labor requirements for patient care in the post

operative recovery area. It is conceivable that

inducing sympathetic blockade in selected cases

(eg, after extremity injury on the battlefield) may

decrease the incidence of phantom limb pain or

reflex sympathetic dystrophy. This would be especially likely if the ultralong duration, microencapsulated local anesthetics prove useful in

clinical practice, so that a one-time blockade procedure could induce a sympathectomy with several days’ duration. Specific nerve block techniques are outlined below, separated by anatomical

region.

Regional Anesthesia of the Head and Neck

Regional anesthesia of the head and neck has

application during trigeminal or occipital nerve

blocks for diagnostic or therapeutic applications for

pain syndromes. Cervical plexus blockade is useful

for surgical procedures on the neck and shoulder.

Maxillary, mandibular, and ocular nerve blocks are

used for procedures on the face.

Cervical Plexus Block

The cervical plexus is formed by loops between

the ventral rami of the upper four cervical nerves.

These emerge as four distinct nerves from the posterior border of the sternomastoid at approximately

its midpoint. The first branch radiates upward and

backward as the lesser occipital nerve to supply

part of the posterior surface of the upper part of the
Anesthesia and Perioperative Care of the Combat Casualty

268

ear and the skin behind the ear; the second branch

runs upward and forward as the great auricular

nerve, which supplies skin over the posterior surface of the ear and the anterior lower third of the ear,

and the angle of the mandible; the third branch, the

anterior cutaneous nerve of the neck, supplies the

skin from the chin to the suprasternal notch; and the

fourth branch, the supraclavicular nerve, supplies

the skin over the inferior aspect of the neck and

clavicle down as far as the area over the second rib.

Laterally, these supraclavicular nerves supply the

skin over the deltoid muscle and posteriorly as far

as the spine of the scapula.41

The branches of the plexus are divided into superficial and deep. The superficial branches pierce

the cervical fascia just posterior to the sternomastoid

and supply the skin of the side of the face and neck.

The deep branches contribute primarily efferent (ie,

motor) fibers to the muscles of the neck and the

phrenic nerve.

Indications. Cervical plexus blockade is useful

for operations on the lateral or anterior neck such as

carotid endarterectomy or thyroidectomy.70 It is

useful for treatment of pain syndromes such as

reflex sympathetic dystrophy.

Anatomy. The dorsal rami supply the muscles of

the back of the head and neck and innervate the

skin from the vertex to the shoulders.71 The ventral

rami of the upper four cervical nerves form the

cervical plexus. This plexus innervates the skin of

the front of the neck, the shoulders, and the upper

chest, together with the neck muscles. The plexus

lies over the upper four cervical vertebrae, deep to

the internal jugular vein and the sternomastoid muscle, and anterior to the scalenus medius

and levator scapulae. The branches of the plexus

divide into superficial and deep. The superficial

branches supply the skin of the side of the face

and neck. The deep branches contribute motor

nerve fibers to the muscles of the neck and phrenic

nerve.72

Technique. Both superficial and deep cervical

plexus blockades can be accomplished using the

following equipment:

• 5-cm, 22-gauge needles; and

• 3 or 4 mL of 1% lidocaine or its equivalent.41

All four branches of the superficial cervical plexus

can be blocked by infiltration at the midpoint of the

posterior border of the sternomastoid. Lidocaine,

1% or its equivalent, can be infiltrated at this area; 5

to 10 mL will be required. This will produce cutaneous analgesia of the anterior and lateral neck

from the mandible to the clavicle.41

The deep cervical plexus blockade is a para-vertebral block of spinal nerves C-2 through C-4 as they

emerge from the foramina in the cervical vertebrae

(Figure 12-4). Each nerve lies in the sulcus in the

transverse processes of these vertebrae.41 A line is

drawn from the mastoid process to Chassaignac’s

tubercle (C-6). This line crosses a line drawn laterally

from the cricoid cartilage, which is at the level of C-4.

Fig. 12-4. When performing a deep cervical plexus block,

note that caudad direction of the needle is essential to

avoid penetration of an intervertebral foramen. Frequent

aspiration is necessary to prevent injection into the vertebral artery. Reprinted with permission from Murphy

TM. Somatic blockade of head and neck. In: Cousins MJ,

Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. 2nd ed. Philadelphia, Pa: JB

Lippincott; 1988: 553.
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269

The C-3 and C-2 nerve roots can be located by dividing

the distance between the mastoid and horizontal line

into thirds.41 The C-5 nerve root lies midway between

the C-6 line at Chassaignac’s tubercle and C-4.

The needles are directed medially and caudally.

Caudad direction is to avoid unintentionally entering the intervertebral foramen and producing a

spinal block. The needle is advanced until the

transverse process is contacted or paresthesias are

obtained. Adequate anesthesia is provided by 3 to

4 mL of 1% lidocaine or the equivalent on each

nerve. Deep cervical plexus block can often be

obtained with injections at just one level with a

larger volume, such as 6 to 8 mL.41

Complications. Complications of cervical plexus

block include phrenic nerve block (a reason to avoid

bilateral cervical plexus block), vertebral artery injection, epidural injection, subarachnoid injection,

and recurrent laryngeal nerve block.44

Occipital Nerve Block

The skin over the posterior extensor muscles of

the neck and occiput is supplied by the posterior

rami of the cervical nerves.41 The greater occipital

nerve is the most prominent nerve supplying this

area. It is sometimes blocked in the treatment of

occipital tension headaches.

Anatomy. The greater occipital nerve can be

blocked as it crosses the superior nuchal line. This

line is identified by locating the greater occipital

protuberance and the mastoid process. The greater

occipital nerve crosses the superior nuchal line one

third of the way between the external occipital

protuberance and the mastoid process.41

Technique. Occipital nerve block is accomplished

using a short needle (2–3 cm, 22- to 25-gauge) after

a sterile skin preparation (Figure 12-5). The greater

occipital nerve is located one third of the way between the greater occipital protuberance and the

mastoid process.41 It lies adjacent (medial) to the

occipital artery, which can be palpated. Infiltration

of 2 to 10 mL of 0.25% bupivacaine or its equivalent

around the artery will provide a block of the greater

occipital nerve.57

The lesser occipital nerve lies approximately 2.5

cm lateral to the greater occipital nerve. It can be

blocked directly above and behind the mastoid process. This block is done by entering the skin vertically, directly at the exit point of the nerve behind

the mastoid process. After definite bony contact

has been established, 2 to 10 mL of local anesthetic

is infiltrated (0.25% bupivacaine or its equivalent).

Complications. The occipital nerve block is associated with few complications, but inadvertent intravenous injection is possible.

Fig. 12-5. In an occipital nerve block,

the anesthetic agent is injected along

an imaginary curved line extending

between the mastoid process and

the greater occipital protuberance.

Reprinted with permission from

Murphy TM. Somatic blockade of

head and neck. In: Cousins MJ,

Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. 2nd ed. Philadelphia, Pa: JB Lippincott; 1988: 552.
Anesthesia and Perioperative Care of the Combat Casualty

270

Maxillary Nerve Block

Block of the maxillary nerve will anesthetize the

skin and deep structures of the middle face including the nasal cavity, the maxillary bone and sinus,

the upper teeth, and the upper part of the mouth

and oral cavity. Indications for maxillary nerve

block include trigeminal neuralgia of the second

branch, pain of maxillary neoplasm, postoperative

pain, atypical facial neuralgia, acute herpes zoster,

and cluster headache.57

Anatomy. The maxillary nerve leaves the cranium through the foramen rotundum, crosses the

pterygopalatine fossa, and enters the orbit through

the inferior orbital fissure, where it becomes the

infraorbital nerve.50,71 Branches of the maxillary

nerve include the posterior, middle, and anterior

superior alveolar nerves.57,72

Technique and Local Anesthetic Drug Dosage. A

7-cm needle is inserted medially at the junction of

the zygoma and the anterior edge of the ramus. The

needle is inclined cephalad and posteriorly. The

needle is advanced to the depth of the sphenoid

bone.57,72 A dose of 4 mL of 1% lidocaine or 0.25%

bupivacaine is used to achieve anesthesia.57

Complications. The only reported complications

are hemorrhage due to injury of the maxillary artery and subarachnoid injection.57,72

Mandibular Nerve Block

Block of the mandibular nerve will anesthetize

the lower jaw and the skin and tissues of the lower

face. The mandibular nerve, which is the largest

branch of the trigeminal nerve, is sensory to the skin

over the lower jaw, posterior face, lower lip, lower

teeth and gums.72 It supplies the motor fibers to the

muscles of mastication.

Anatomy. The nerve divides into an anterior and

a posterior trunk after leaving the foramen ovale.

The sensory fibers of the anterior trunk run in the

buccal nerve, which is distributed with branches

of the facial nerve supplying the skin and mucous membrane on either side of the buccinator

muscle. The posterior trunk divides into three

branches: the auriculotemporal, the lingual, and

the inferior alveolar nerves.72 The auriculotemporal supplies the skin over the temporal region and external auditory meatus. The lingual

supplies the mucous membrane of the floor of the

mouth and anterior two thirds of the tongue,

in addition to the lingual surface of the lower

gums.72 The inferior alveolar enters the mandibular

foramen and runs in the mandibular canal supplying the lower teeth. At the mental foramen it

gives off a lateral branch, the mental nerve, which

supplies the skin over the anterior jaw and lower

lip.72

Technique and Local Anesthetic Drug Dosage.

To perform this block, a wheal is raised 0.5 cm

below the zygomatic arch between the coronoid process and the condyle of the mandible. The needle is

inserted at right angles to the skin until it contracts

the pterygoid plate at a depth of 3 to 4 cm. It is then

withdrawn a few millimeters and redirected 20°

posteriorly until a paresthesia is elicited. Anesthetic drugs such as 5 mL of 2% lidocaine or 0.5%

bupivacaine or their equivalent are used.72

Trigeminal Nerve Block

The trigeminal nerve, the largest of the cranial

nerves, can be blocked for treatment of trigeminal

neuralgia or postherpetic pain. The sensory supply

to the face and anterior two thirds of the scalp is

from the trigeminal nerve. It is formed by the union

of a sensory and a motor root. This union is called

the trigeminal, or Gasserian, ganglion. The trigeminal nerve supplies the skin of the face and scalp and

the muscles of mastication via its three main

branches: (1) the ophthalmic nerve, which leaves

the cranium through the superior orbital fissure; (2)

the maxillary nerve, which leaves through the foramen rotundum; and (3) the mandibular nerve, which

leaves through the foramen ovale. All three nerves

can be blocked with a single injection through the

foramen ovale.72

Because the trigeminal nerve block is complex

and possible complications include subarachnoid

injection of local anesthetic at the base of the brain,

we recommend that this block should not be performed in far-forward battlefield conditions. Radiographic capabilities to perform the block under

radiographic control are required.

Ocular Nerves

Surgery of the eye can be done by numerous local

techniques, including the following72:

• The cornea can be anesthetized by topical

local anesthesia.

• The conjunctiva can be anesthetized by local infiltration.

• The globe can be anesthetized by retrobulbar injection.
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271

• The nasociliary nerve supplies the skin and

mucous membrane of the nose, cornea and

conjunctiva; it can be blocked at the medial

wall of the orbit.

• The supraorbital nerve supplies the upper

eyelid and conjunctiva; it can be blocked at

the supraorbital foramen.

• The infraorbital nerve supplies the skin of

the ala of the nose, the lower eyelid, the

cheek, and the upper lip; it can be blocked

as it enters the face through the infraorbital

foramen.

These procedures are not commonly done by most

anesthetists, and it is recommended that they be

performed only by personnel who are facile with

local ophthalmic anesthesia.

Regional Anesthesia of the Airway

The nasal mucosa is innervated by fibers of the

sphenopalatine ganglion via a branch of the middle

division of the fifth cranial nerve. Branches of the

fifth cranial nerve continue caudad to provide

sensory innervation to the superior pharynx,

uvula, and tonsils. Transmucosal topical application of local anesthetic can be used to anesthetize

this region.70

Sensory innervation of the oral pharynx and

supraglottic regions below the sphenopalatine fiber

distribution is from branches of the glossopharyngeal nerve. These nerves lie laterally on each side of

the pharynx in the region of the posterior tonsillar

pillars. Topical anesthesia of these branches in the

mouth and throat is an effective method of providing anesthesia to the submucosal branches of the

glossopharyngeal nerve.70

The larynx is innervated by the superior laryngeal branch of the vagus nerve above the vocal

cords. Below the vocal cords, the recurrent laryngeal nerve provides sensory innervation and supplies motor innervation for all but one intrinsic

laryngeal muscle.70

Superior Laryngeal Nerve Block

The superior laryngeal branch of the vagus nerve

is blocked as it sweeps around the inferior border of

the greater cornu of the hyoid bone.41 This can be

palpated by pressing on the opposite greater cornu

of the hyoid bone, which will displace the opposite

cornu toward the side to be blocked.41 A 2.5-cm, 25-

gauge needle is walked from the inferior border of

the greater cornu of the hyoid near its tip, and 3 mL

of local anesthetic is infiltrated both superficially

and deep to the thyrohyoid membrane (Figure 12-

6). This procedure is repeated bilaterally. This

block will produce anesthesia over the inferior aspect of the epiglottis and laryngeal inlet as far down

as the vocal cords.41

Transtracheal Block

To produce anesthesia below the cords, a

transtracheal puncture can be performed. A 20-

gauge catheter is introduced through the cricothyroid membrane in the midline. After entry into

the trachea is confirmed by aspiration of air, the

catheter is advanced from the needle. Correct placement is confirmed again by aspiration of air, followed by rapid injection of 3 to 5 mL of local anesthetic, which produces a cough reflex. For this

block, 2% to 4% lidocaine is commonly employed.

Complications of the transtracheal block include

the possibility of aspiration in certain patients due

to the loss of the protective airway reflexes.

Nerve Blocks for Upper Extremity Surgery

Injuries to the upper extremities are common

during wartime and may be amenable to regional

anesthetic techniques during surgical repair. Regional anesthesia has the advantage of providing postoperative pain control and blockade of the

sympathetic nervous system with selected blocks.

Knowledge of the anatomy of the upper extremity

is crucial for performance of regional anesthetic

blockade.

The brachial plexus can be blocked at three locations41:

1. the interscalene approach, in which a

needle is inserted in the interscalene groove

at the level of the cricoid cartilage and

advanced until the tubercle of C-6 is contacted or until a paresthesia is elicited;

2. the supraclavicular approach, in which the

needle is inserted into the interscalene

groove 1 cm or until a paresthesia is elicited; and

3. the axillary approach, which carries the

least risk of pneumothorax.

The interscalene and supraclavicular approaches

are more difficult to perform and therefore are less

frequently used than the axillary approach.
Anesthesia and Perioperative Care of the Combat Casualty

272

Fig. 12-6. Technique for anesthetizing the larynx and trachea such as

might be used in performing bronchoscopy. The superior laryngeal nerve

is blocked as it passes anterior and

inferior to the posterior cornu of the

hyoid bone. Anesthesia of the tracheal

mucosa is obtained by injecting the

agent directly through the space between the thyroid and cricoid cartilages. Reprinted with permission

from Murphy TM. Somatic blockade

of head and neck. In: Cousins MJ,

Bridenbaugh PO. Neural Blockade in

Clinical Anesthesia and Management of

Pain. 2nd ed. Philadelphia, Pa: JB

Lippincott; 1988: 549

The needle is advanced through the artery, which is

deliberately entered. The needle is advanced until

aspiration confirms it has passed just posterior to

(ie, through) the artery, at which time one half of the

local anesthetic solution is injected. The needle is

then withdrawn until aspiration confirms it is just

anterior to the artery; then the other half of the

solution is injected.

The musculocutaneous nerve is blocked by infiltration of 5 mL of anesthetic into the coracobrachial

muscle. Median cutaneous and intercostobrachial

nerves can be blocked by subcutaneous infiltration

of 10 mL of anesthetic solution in a half-ring around

the medial aspect of the arm.

Local Anesthetic Drug Dosages. To achieve nerve

blockade, the anesthesiologist should inject 30 to 40

mL of local anesthetic solution (1% lidocaine, 0.25%

bupivacaine, 1.5% mepivacaine); in children, 10 to

20 mL should be injected.

Complications. When the axillary approach is

used, complications are rare but include neuropathy,

hematoma, and intravascular injection.

Brachial Plexus Block: The Axillary Approach

Innervation of the upper extremity is from nerve

roots of C-5 through T-1, which form the brachial

plexus. The median and musculocutaneous nerves

lie above the axillary artery; the ulnar and radial

nerves lie below and behind the artery.

Technique. The axillary approach to a brachial

plexus block is performed using the following equipment:

• 23-gauge, 11⁄2-in., short, beveled needle;

• extension tubing; and

• 20-mL syringes.

The patient is in the supine position with the arm

abducted and elbow flexed (Figure 12-7). The arm

is externally rotated, so that the hand lies alongside

the patient’s head. The axilla is prepared and draped

for surgery. The axillary artery is located as high as

is practical in the axilla as it courses in the groove

between the coracobrachialis and triceps muscles.
Regional Anesthesia

273

a b

Fig. 12-7. The axillary approach to producing brachial plexus blockade. (a) The edge of the pectoralis major muscle and

the axillary artery are the anatomical landmarks. (b) The anesthetic agent is injected deep to the axillary sheath of the

brachial plexus. Reprinted with permission from Bridenbaugh LD. The upper extremity: somatic blockage. In: Cousins

MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. 2nd ed. Philadelphia, Pa: JB

Lippincott; 1988: 401.

Brachial Plexus Block: The Interscalene Approach

The brachial plexus runs between the anterior

and middle scalene muscles in the neck, where their

fascia forms a perivascular sheath. The perivascular

sheath is reached during this approach to a brachial

plexus block by inserting a needle into the sheath at

the sixth cervical vertebra, which corresponds to

the level of the cricoid cartilage.

Technique. The patient is in the supine position,

with the head rotated away from the side to be

blocked (Figure 12-8). The groove between the

anterior and middle scalene muscles is palpated

behind the sternocleidomastoid muscle. The anterior scalene is immediately behind the sternomastoid, and a groove is palpable between the anterior

and the middle scalene muscles.

A 3- to 4-cm needle is inserted perpendicular to the

skin at the level of the cricoid cartilage (C-6) in the

interscalene groove. The needle is slowly advanced

until a paresthesia felt below the shoulder is elicited or

a transverse spinous process is felt. If bone is contacted, the needle can be walked laterally along the

transverse process until a paresthesia is elicited. A

nerve stimulator with insulated needle may be used,

instead of the anesthesiologist’s relying on the

casualty’s perception of paresthesia. When it is in

close proximity to the plexus, the nerve stimulator

should elicit muscle twitching in the arm or hand.72

With an assistant using frequent aspiration, 30 to

40 mL of 1.5% mepivacaine (or its equivalent) is

injected in fractionated doses. The patient’s perception of pain while the anesthetic is being injected

may indicate a direct intraneural injection, in which

case the needle should be withdrawn about 1 mm

and the injection should be repeated.

Complications. Complications of interscalene

brachial plexus block include spinal or epidural

blockade by inadvertent penetration of the epidural

or dural spaces or entry via an intervertebral foramen, intraneural injection, and intraarterial or

venous injection.

Brachial Plexus Block: The Supraclavicular

Approach

The supraclavicular approach to brachial plexus

block involves injecting local anesthetic into the

perivascular sheath that surrounds the plexus at the

level of the clavicle. When the brachial plexus

passes between the clavicle and the first rib, it is

joined by the subclavian artery, which runs deep to

the anterior scalene muscle. The three trunks (superior, middle, and inferior) of the brachial plexus lie

Axillary Sheath of Axillary Artery

Brachial Plexus

Ulnar Nerve
Anesthesia and Perioperative Care of the Combat Casualty

274

Fig. 12-8. (a) A needle is being placed in the perivascular sheath surrounding the brachial plexus. The anesthesiologist

is palpating the interscalene groove to facilitate needle placement. (b) A flexible cannula is used during injection to

ensure that the needle remains immobile after correct placement has been achieved. (c) The anatomy of the brachial

plexus and its perivascular sheath at the C-6 level is seen in detail. Reprinted with permission from Scott DB. Techniques

of Regional Anaesthesia. East Norwalk, Conn: Appleton & Lange; 1989: 93. Drawings by Paol Buckhöj.

a

c

b

in a vertical plane lateral to the subclavian artery.72

Technique. The patient is in the supine position,

with the arm on the side to be injected pulled downward to depress the clavicle and shoulder (Figure

12-9). The subclavian artery can be palpated above

the midportion of the clavicle. The interscalene

groove is palpated posterior to the sternocleidomastoid muscle.

A 4-cm-long needle is inserted lateral to the subclavian artery and directed vertically and caudally.

It is advanced slowly until the patient feels a

paresthesia below the shoulder. If the needle contacts the first rib, the needle is withdrawn and the

process is repeated as close as possible to the artery.

A nerve stimulator can be used, and muscle movement in the arm or hand would indicate correct

placement.72

When proper needle placement is obtained, fractionated doses of 1.5% mepivacaine (or its equivalent) are injected, using a flexible catheter, to a total

dose of 44 mL.

Complications. Complications of this technique

include arterial puncture, intraneural injection,

pneumothorax, and spinal or epidural blockade.
Regional Anesthesia

275

a c

b

Fig. 12-9. (a) Needle placement into the perivascular sheath surrounding the brachial plexus and the subclavian artery

at the level of the clavicle. (b) Palpation of the interscalene groove at the midportion of the clavicle and identification

of the subclavian artery. (c) The three trunks of the brachial plexus and their relationship to the clavicle and

interscalene muscles. Reprinted with permission from Scott DB. Techniques of Regional Anaesthesia. East Norwalk,

Conn: Appleton & Lange; 1989: 99. Drawings by Paol Buckhöj.

Intravenous Regional Anesthesia: Bier’s Method

Bier’s method of achieving intravenous regional

anesthesia (ie, the Bier block) allows analgesia and

muscle relaxation in an extremity. It is performed

by intravenously administering a local anesthetic

distal to a tourniquet that provides complete vascular occlusion. We do not recommend the use of

intravenous regional anesthesia for surgical procedures of the lower extremity. The high volumes of

local anesthetic required to produce an adequate

nerve block risk local anesthetic systemic toxicity

and therefore make this technique a less desirable

choice than specific nerve blocks.73 Because the

procedure is not infrequently used on the lower

extremity, however, it is discussed here for the sake

of completeness.

Technique. An intravenous catheter is placed in

the distal extremity. A plastic extension tubing

from the catheter is attached to a 50-mL syringe. A

pneumatic double tourniquet is placed proximal to

the operative site. The extremity is exsanguinated

by the application of an Esmarch bandage or by

elevation. The bandage is applied distal to proximal. The tourniquet is inflated after exsanguination

and before removal of the bandage. The proximal

pneumatic tourniquet is inflated above systolic pressure. Pulses are checked after inflation to confirm

occlusion of circulation (usually 250–300 mm Hg in

the arm and 350–400 mm Hg in the leg).

The local anesthetic solution is then injected. For

short procedures, the intravenous catheter is removed at this point; for longer procedures, the

cannula is left in place and the local anesthetic

solution is reinjected after 90 minutes. The area

anesthetized includes the distal extremity up to the

area of the proximal tourniquet. If tourniquet discomfort begins, the distal tourniquet can be inflated, as this area is already anesthetized and the

proximal tourniquet is deflated. Tourniquet pain

is usually the limiting factor for success of this

technique.
Anesthesia and Perioperative Care of the Combat Casualty

276

If surgery lasts longer than 40 minutes, the tourniquet can be deflated as a single maneuver. Between 20 and 40 minutes, the cuff can be deflated,

reinflated immediately, and finally deflated after a

minute to reduce the sudden absorption of anesthetic into the systemic circulation. The tourniquet

is left inflated for at least 20 minutes.70

A separate intravenous site for injection of resuscitation drugs is needed for this block, as well as

ready availability of all needed equipment.

Anesthetic Drug Dosages and Complications. The

duration of action of the local anesthetic agent is

limited by tourniquet time rather than the agent.

The amount of drug given depends on the size of the

extremity. Average doses are 40 to 50 mL of 0.5%

lidocaine for an arm, and 100 mL of 0.25% lidocaine

for a leg. Agents should not be mixed with vasoconstrictors. Local anesthetic drug toxicity can be seen if

the tourniquet fails or is relieved too quickly. Nerve

damage secondary to tourniquet application can be

seen. Tourniquet time should not exceed 2 hours.

Relative Contraindications. Relative contraindications to the Bier block include distal infection of

the extremity, ischemia of the involved extremity,

heart block, and seizure disorder.

Sole-Anesthetic Nerve Blocks for Lower

Extremity Surgery

Neural blockade of the lower extremity may be

useful to provide preoperative analgesia, intraoperative anesthesia as the sole anesthetic or as a supplement to general anesthesia, and postoperative analgesia.73 Some nerve blocks are suited for all three of

these uses, while others provide good analgesia but

may not be acceptable for intraoperative anesthesia.

As has been described earlier in this chapter,

lower extremity anesthesia can be obtained by spinal or epidural techniques. Additional nerve blocks

that may be useful for preoperative analgesia,

intraoperative general anesthesia supplementation,

postoperative analgesia, or as the sole anesthetic are

described in this section. Combined peripheral nerve

block techniques are indicated if spinal or epidural

anesthesia are undesirable.73 Advantages of a combined peripheral nerve block technique include the

blockade of only one leg, smaller hemodynamic

changes owing to the limited sympathectomy, and

avoidance of major conduction anesthesia. The

major disadvantage of the technique is the need for

at least two needle insertions to block separately the

peripheral nerves formed by the lumbar plexus and

those formed by the sacral plexus. Individual techniques are discussed in the following section.

Lumbar Plexus Block

Blockade of the lumbar plexus provides unilateral analgesia in the distribution of the femoral,

lateral femoral cutaneous, and obturator nerves.

Patients with trauma to or surgical procedures of

the hip or thigh may therefore benefit from this

block. Lumbar plexus block is contraindicated in

Fig. 12-10. The 3-in-1 lumbar plexus blockade. (a) The

anatomical landmarks are the inguinal ligament (2) as it

extends between the anterior superior iliac spine and

pubic tubercle and the femoral artery (1). (b) The needle

is inserted 1 to 1.5 cm laterally to the femoral artery and

advanced in a cranial direction. Continuous infusion of

anesthetic agent through a catheter is desirable. Reprinted

with permission from Astra Chemicals GmbH, Zenz M,

Hoerster W, Niesel HC, Kreuscher H, eds; DeKornfeld TJ,

trans. Regional Anesthesia. 2nd ed. St. Louis, Mo: Mosby–

Year Book; 1990: 109, 111.

b

a
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277

the presence of local infection, coagulation abnormality, immunosuppression, and perhaps neurological deficits involving the ipsilateral limb. Two

techniques have been described: the Winnie “3-in1” paravascular approach from the femoral canal,74

and the lumbar paravertebral approach to the lumbar plexus blockade.73

Winnie 3-in-1 Paravascular Approach. The

Winnie 3-in-1 blockade can be performed with the

patient in the supine position (Figure 12-10). This

technique utilizes the fascial plane that the femoral

nerve travels in as it crosses the pelvis. A large

quantity of local anesthetic is injected in this plane

so that it will spread upward into the pelvis and

anesthetize the obturator and lateral femoral cutaneous nerves where they travel in conjunction with

the femoral nerve. Paresthesias are usually necessary for this approach, as it is essential to have the

Fig. 12-11. Lumbar plexus block at the psoas compartment.

(a) The iliac crests are used to determine the spinous process

of the 4th lumbar vertebra. (b) A 15-cm long needle is inserted

at a point 5 cm lateral to midline and 3 cm caudad to the 4th

lumbar spinous process. The needle is advanced until the

lateral process of the 5th lumbar vertebra is reached (needle

point 1). The needle is then advanced in a cranial direction

superior to the vertebral process and an injection made (needle

point 2). Reprinted with permission from Brown DL. Atlas of

Regional Anesthesia. Philadelphia, Pa: WB Saunders; 1992: 77, 78.

needle exactly in the plane of the nerve. This block

is performed by inserting the needle in a cephalad

manner alongside the femoral artery angled at about

45° so that it passes under the inguinal ligament.

After obtaining a paresthesia, 40 mL of anesthetic

solution is injected incrementally.70 During the injection, the anesthesiologist’s index finger is moved

to a point just distal to the needle, where firm

pressure is applied to prevent retrograde flow of

the injected local anesthetic.

Lumbar Paravertebral Approach. The lumbar

paravertebral approach to the lumbar blockade may

be used if the patient can be turned, because this

approach is more often successful in blocking the

obturator nerve (Figure 12-11). For continuous

blockade, a Tuohy needle is inserted 3 cm lateral to

the midline at the level of the L-3–L-4 interspace

and is advanced until the transverse process of

b

a
Anesthesia and Perioperative Care of the Combat Casualty

278

L-4 is contacted. The needle is then walked superiorly and laterally into the substance of the quadratus

lumborum muscle, and is then advanced, using the

loss-of-resistance technique, into the fascial plane

between the quadratus lumborum and psoas

muscles. The lumbar plexus lies within this psoas

compartment. An epidural catheter may be passed

into the compartment. Injection of 0.5 mL/kg of

local anesthetic solution should provide a reliable

block. The concentration of local anesthetic used

depends on the degree of motor block desired.

Continuous infusions of local anesthetic at 0.25

mL/kg/h may be used to continue the block.73

Femoral Nerve Block

Surgical use of femoral nerve block includes operations of the anterior portion of the thigh, both

superficial and deep (Figure 12-12).41 As with sciatic nerve block, the femoral nerve block is usually

part of the combined block approach, incorporating

not only sciatic but also lateral femoral cutaneous

and obturator nerves.

The femoral nerve (which is composed of fibers

arising from the spinal segments L-2–L-4) proceeds

from the lumbar plexus in the groove between the

psoas major and iliac muscles, where it enters the

thigh by passing deep to the inguinal ligament. The

femoral nerve lies anterior to the iliopsoas muscle

and slightly lateral to the femoral artery.

Technique. The femoral nerve block may be

accomplished using the following equipment:

• 11⁄2-in., 22-gauge needle; and

• 20-mL syringe.

Palpate the femoral artery just below the inguinal

ligament, and advance the needle toward the lateral

border of the artery.41 If a paresthesia is not obtained, redirect the needle to fan medial to lateral

until a paresthesia is obtained. Then stabilize the

needle and, after negative aspiration, inject 10 to

15 mL of local anesthetic solution. If a paresthesia

is not obtained, the nerve can be blocked by injecting in a fanwise manner, medial to lateral, from the

lateral border of the femoral artery.

Local Anesthetic Drug Dosages and Complications. Any anesthetic agent suitable for peripheral

nerve blockade, 10 to 20 mL, is suitable. Hematoma at the site is possible because of the proximity

to a major artery and vein. Residual nerve involvement is possible but rare, causing a dysesthesia or

paresis.

Sciatic Nerve Block

Sciatic nerve block is usually combined with femoral, obturator, or lateral femoral cutaneous nerve

block to provide complete anesthesia of the lower

extremity.73 The sciatic nerve supplies sensory innervation to the posterior thigh and the entire leg

and foot from just below the knee. The nerve (from

spinal segments L-4–S-3) arises from the sacral

plexus and passes from the pelvis through the

sacrosciatic foramen beneath the lower margin of

the piriformis muscle and between the tuberosity

of the ischium and the greater trochanter of the

femur (Figure 12-13).41 The sciatic nerve becomes

Fig. 12-12. Anatomy of the femoral nerve block. The

inguinal ligament and the femoral artery are the landmarks. Injection is made lateral to the artery (2) after a

femoral nerve paresthesia is produced (1). Reprinted

with permission from Brown DL. Atlas of Regional Anesthesia. Philadelphia, Pa: WB Saunders; 1992: 95.
Regional Anesthesia

279

superficial at the lower border of the gluteus maximus muscle. From there, it courses down the posterior aspect of the thigh to the popliteal fossa,

where it divides into the tibial and common peroneal nerves.73

Technique. The sciatic nerve block is performed

with the following equipment:

• 21- or 22-gauge needle, 10 to 20 cm long; or

• 22-gauge, Teflon-coated (polytetrafluoroethylene, manufactured by Du Pont Polymers, Wilmington, Del.) stimulator needle

with nerve stimulator; and

• 10-mL syringe.

The patient is relaxed and lying on the side that

is not to be blocked. The upper leg is flexed at the

hip and at the knee so that the heel rests on the knee

of the lower, extended leg. The landmarks are

connected with a line (greater trochanter, superior–

posterior iliac spine). From the middle of this line,

a line is drawn inferiorly at right angles and intersects a line drawn between the tip of the coccyx and

the greater trochanter at about 3 cm. This point is

marked for needle insertion. A 22-gauge, 15-cm

long needle is introduced through a skin wheal at

right angles to the skin and is advanced in the

direction of the sacrosciatic foramen, through the

gluteus maximus. Paresthesias, which may extend

to the sole of the foot, prove the correct position of

the needle. Electrical stimulation with a needle

stimulator facilitates placement. After aspiration,

20 to 30 mL of the local anesthetic is injected.

Local Anesthetic Drug Dosages and Complications. The sciatic nerve block can be achieved with

20 to 30 mL of 1.5% lidocaine or 0.5% bupivacaine.

No significant complications secondary to this block

have been documented. Residual dysesthesias have

been reported but are usually self-remitting.41

Sciatic Nerve Block at the Popliteal Fossa

Sciatic nerve block from the popliteal fossa approach will provide unilateral anesthesia for procedures below the level of the knee, with the exception of the saphenous nerve distribution, which is a

continuation of the femoral nerve, originating from

the lumbar plexus (Figure 12-14).41,73 The popliteal

approach is especially amenable to a catheter technique.

Technique. Sciatic nerve block from the popliteal

fossa approach can be accomplished using the following equipment:

• 18-gauge, 21⁄2-in. catheter; and

• 20-gauge epidural catheter.

Insert the catheter over a blunt stylet 10 cm above

the popliteal crease in the midline at an angle of

approximately 30° to the skin. The needle is advanced in an anterior and cephalad direction until a

fascial “pop” is felt. The stylet is then withdrawn

and 20 mL of local anesthetic solution is injected

through the catheter in incremental doses. A 20-

gauge epidural catheter is then threaded through

the short catheter; the short catheter is removed;

and the epidural catheter is fixed in place using a

sterile, transparent dressing. The sciatic nerve is

anesthetized at its bifurcation to the common peroneal and tibial nerves.

Contraindications. Sciatic nerve block from the

popliteal fossa approach is contraindicated in the

presence of local or systemic infection, coagulation

abnormality, immunosuppression, and unstable

neurological deficits.41

Complications. The sciatic nerve block may be

complicated by needle trauma, infection, and inadequate nerve block.

Fig. 12-13. The sciatic nerve block. A line is drawn between the posterior superior iliac spine and the greater

trochanter. Then a line is dropped from its midpoint at

right angles, which intersects a line drawn between the

tip of the coccyx and the greater trochanter at about 3 cm.

1: posterior-superior iliac spine; 2: greater trochanter

muscle; 3: tip of coccyx; 4: sciatic nerve. Reprinted with

permission from Astra Chemicals GmbH, Zenz M,

Hoerster W, Hiesel HC, Kreuscher H, eds; DeKornfeld

TJ, trans. Regional Anesthesia. 2nd ed. St. Louis, Mo:

Mosby–Year Book; 1990: 116, 117.
Anesthesia and Perioperative Care of the Combat Casualty

280

Fig. 12-14. Sciatic nerve block at the popliteal fossa. The

injection is made in the posterior midline about 10 cm

cranial to the transverse crease in the skin of the popliteal fossa. Reprinted with permission from Brown DL.

Atlas of Regional Anesthesia. Philadelphia, Pa: WB Saunders;

1992: 112.

Lateral Femoral Cutaneous Nerve Block

The lateral femoral cutaneous nerve supplies the

skin over the anterolateral aspect of the thigh as low

as the knee. A posterior branch pierces the fascia

lata and passes backward to supply the skin on the

lateral side of the thigh. One of the terminal anterior branches forms part of the patellar plexus and

must also be blocked for operations on the knee.

The lateral femoral cutaneous nerve (L-2–L-3)

emerges at the lateral border of the psoas muscle at

a level lower than the ilioinguinal nerve.41 It passes

obliquely under the iliac fascia and across the iliac

muscle to enter the thigh deep to the inguinal ligament at a point 1 to 2 cm medial to the anterior

superior iliac spine.

Technique. Lateral femoral cutaneous nerve block

can be accomplished using the following equipment:

• 22-gauge, 11⁄2 in. needle; and

• 10-mL syringe.

The patient is placed in the supine position. After

palpation of the anterior superior iliac spine, a skin

wheal is placed 2 to 3 cm inferior and 2 to 3 cm

medial to it.41 A 3- to 4-cm needle with syringe

attached is inserted perpendicular to the skin (Figure 12-15). After the needle passes through the skin,

the anesthesiologist feels firm fascia lata, followed

by a sudden release as the needle passes through.

Fig. 12-15. The lateral femoral cutaneous nerve block as it passes under the

inguinal ligament at a point about 2 to

3 cm inferior and 2 to 3 cm medial to

the anterior superior iliac crest. Reprinted with permission from Brown

DL. Atlas of Regional Anesthesia. Philadelphia, Pa: WB Saunders; 1992: 100.
Regional Anesthesia

281

Ten milliliters of a local anesthetic solution can be

deposited fanwise as the needle is moved upward

and downward, depositing solution both above and

below the fascia.

An alternative technique is to direct the needle

through the skin wheal in a slightly lateral and

cephalad direction to strike the iliac bone just medial and inferior to the anterior superior iliac spine

where the nerve emerges. Ten milliliters of local

anesthetic is deposited in a medial fanwise fashion

at this point.

Local Anesthetic Dosage and Complications.

Any anesthetic agent suitable for peripheral nerve

block can be used, in the amount of 10 mL. With the

exception of remotely possible dysesthesia or

hypoesthesia, there are no known risks with this

nerve block.41

Ankle Block

The ankle block provides anesthesia for the foot

by blocking five nerves at the level of the malleoli:

the posterior tibial, sural, superficial peroneal, deep

peroneal, and saphenous nerves.41 The latter three

innervate the dorsum of the foot (Figure 12-16).

The tibial nerve (composed of fibers from L-4–S3), the larger of the two branches of the sciatic nerve,

reaches the distal part of the leg from the medial

side of the Achilles tendon, where it lies behind the

posterior tibial artery.41 The medial branch supplies the medial two thirds of the sole and plantar

portion of the medial three and one half toes, up to

the nail. The lateral branch supplies the lateral one

third of the sole and plantar portion of the lateral

one and one half toes.

The sural nerve is a cutaneous nerve that arises

through the union of a branch from the tibial nerve

and one from the common peroneal nerve. It proceeds

subcutaneously along the short saphenous vein behind and below the lateral malleolus to supply the

lower posterolateral surface of the leg, the lateral

side of the foot, and the lateral part of the fifth toe.

The superficial peroneal nerve (composed of fibers from L-4–S-2) perforates the deep fascia on the

anterior aspect of the distal two thirds of the leg and

runs subcutaneously to supply the dorsum of the

foot and toes, except for the contiguous surfaces of

the great and second toes.

The deep peroneal nerve (composed of fibers

from L-4–S-2) courses down the anterior aspect

of the interosseous membrane of the leg and continues midway between the malleoli onto the dorsum

of the foot. It innervates the short extensors of the

toes as well as the skin on the adjacent areas of

the first and second toes. The anterior tibial artery

lies medial to the nerve, as does the tendon of the

extensor hallucis longus muscle.

The saphenous nerve is the sensory terminal

branch of the femoral nerve. It becomes subcutaneous at the lateral side of the knee joint. It follows the

great saphenous vein to the medial malleolus and

supplies the cutaneous area over the medial side of

Fig. 12-16. Complete anesthesia of the foot can be obtained by blocking five nerves as they pass caudad to the

ankle. The posterior tibial nerve is blocked near the

posterior tibial artery as it passes the medial malleolus.

The deep peroneal nerve is blocked near the dorsalis

pedis artery. The same anterior needle site on the dorsum

of the foot is used to infiltrate the tissues around the

saphenous and superficial peroneal nerves. The sural

nerve is blocked near the lateral malleolus. Needles labeled 1, 2, and 3 show sequence of infiltration. Reprinted

with permission from Brown DL. Atlas of Regional Anesthesia. Philadelphia, Pa: WB Saunders; 1992: 119.
Anesthesia and Perioperative Care of the Combat Casualty

282

the lower leg anterior to the medial malleolus and

the medial part of the foot.41

Technique. The ankle block can be accomplished

using the following equipment:

• 22- to 25-gauge, 11⁄2 in. needle; and

• 10-mL syringe.

The technique is modified according to the nerve to

be blocked.

Posterior Tibial Nerve. The needle is introduced

just posterior to the posterior tibial artery and is

advanced until a paresthesia to the sole of the foot

is elicited, at which point 5 mL of local anesthetic

solution is injected.41

Sural Nerve. The needle is advanced into the

groove between the lateral malleolus and the calcaneus, where 5 mL of local anesthetic solution is

injected.

Saphenous Nerve. Infiltration of 5 mL of local

anesthetic solution in the area where the saphenous

vein passes anterior to the medial malleolus blocks

this nerve.

Deep Peroneal Nerve. This is the major nerve to

the dorsum of the foot, and it is blocked by placement of 5 mL of local anesthetic solution just lateral

to the anterior tibial artery.

Superficial Peroneal Branches. A subcutaneous

ridge of anesthetic solution (5–10 mL) is placed

between the anterior tibial artery and the lateral

malleolus.

Local Anesthetic Drug Dosages and Complications. Any anesthetic agents suitable for peripheral

nerve block can be used, in the amounts specified

above. Epinephrine-containing solutions are not

used because of possible end-artery vasoconstriction and subsequent tissue ischemia. No major

complications have been reported.41

SUMMARY

The techniques for regional anesthesia find potential application in several phases of combat casualty care: analgesia in the preoperative phase,

intraoperative use as the sole anesthetic or as a

supplement to general anesthesia, and analgesia in

the postoperative phase. The most important benefit of regional anesthesia is that the deleterious

effects of general anesthesia, such as loss of airway

reflexes and respiratory depression requiring prolonged observation, are avoided. Furthermore, the

quality of analgesia provided by regional blockade

is superior to other forms of pain relief because local

anesthetics completely block afferent and efferent

nerve impulses.

Blockade of afferent impulses may have benefits

that go beyond simple analgesia; the neurohormonal response to injury is itself blunted. The

chemical agents used in regional anesthetics consist

of a hydrophilic secondary or tertiary amine group

bound to a lipophilic aromatic ring joined by either

an amide or an ester linkage. The propensity for the

hydrophilic group to ionize, as measured by the

pKa, is an important determinate of potency; the

higher the pKa, the greater the ionization and the

longer the duration of action. This relationship

arises from the fact that although passage of the

anesthetic agent through the lipid myelin sheath of

a nerve fiber depends upon lipid solubility, analgesia is caused by alterations in the structure of the

proteins that constitute the sodium channels of the

nerve axon. This latter effect depends on the binding of the ionized form of the hydrophilic group

with receptor proteins.

Regional anesthetic techniques are determined

by knowledge of anatomy and the nature of

the planned surgery. Since the extremities are the

most common site of war wounds, regional techniques would appear to be especially applicable.

The epidural and spinal techniques are the most

versatile regional procedures. They can be used for

extensive abdominal and lower extremity operations, although they are contraindicated in the presence of severe systemic infection or uncorrected

hypovolemia. Nerve blocks for specific anatomical regions, which with an experienced provider

might find application in combat casualty care,

are the brachial plexus block for injuries of

the upper extremity and the sciatic and femoral

nerve blocks for injuries of the legs. Intravenous

regional anesthesia using the Bier method is especially useful in treating isolated injuries of the hand

or forearm. Perhaps the most common technique

using local anesthetics is also the simplest: local

infiltration of the wounds, which is especially useful when a few, small, soft-tissue wounds require

treatment.
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283

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18. Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L. Myocardial ischemia in untreated hypertensive

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20. Pflug AE, Murphy TM, Butler SH, Tucker GT. The effects of postoperative peridural analgesia on pulmonary

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59:473–477.

22. Hillman DR, Rung GW, Thompson WR, Davis NJ. The effect of bupivacaine scalp infiltration on the

hemodynamic response to craniotomy under general anesthesia. Anesthesiology. 1987;67:1001–1003.

23. Hoar PF, Hickey RF, Ullyot DJ. Systemic hypertension following myocardial revascularization. A method of

treatment using epidural anesthesia. J Thorac Cardiovasc Surg. 1976;71:859–864.

24. Klassen GA, Bramwell RS, Bromage PR, Zborowska-Sluis DT. Effect of acute sympathectomy by epidural

anesthesia on the canine coronary circulation. Anesthesiology. 1980;52:8–15.

25. Austin KL, Stapleton JV, Mather LE. Multiple intramuscular injections: A major source of variability in

analgesic response to meperidine. Pain. 1980;8:47–62.

26. Bennett RL, Batenhorst RL, Bivins BA, Bell RM, Groves DA, Foster TS. Patient–controlled analgesia—a new

concept of postoperative pain relief. Ann Surg. 1982;195:700–705.

27. White PF. Use of patient-controlled analgesia for management of acute pain. JAMA. 1988;259:243–247.

28. Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology. 1984;61:276–310.

29. Hondeghem LM, Miller RD. Local anesthetics. In: Katzung BG, ed. Basic and Clinical Pharmacology. East

Norwalk, Conn: Appleton & Lange; 1989: 315–322.

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2nd ed. New York: Churchill Livingstone; 1986: 1237–1242.

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Stratton; 1976.

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Pharmacology. East Norwalk, Conn: Appleton & Lange; 1989: 209–227.

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Therapeutics, 6th ed. New York, NY: MacMillan; 1980: 300–321.

34. O’Connor CJ. Thoracic epidural analgesia: Physiologic effects and clinical applications. J Cardiothorac Vasc

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35. Lema MJ, Sinha I. Thoracic epidural anesthesia and analgesia. Pain Digest. 1994;4:3–11.

36. Tuman KJ, McCarthy RJ, March RJ, et al. Effects of epidural anesthesia and analgesia on coagulation and

outcome after major vascular surgery. Anesth Analg. 1991;73:696–704.

37. Sharrock NE, Mineo R, Urquhart B, Salvati EA. The effect of two levels of hypotension on intraoperative blood

loss during total hip arthroplasty performed under lumbar epidural anesthesia. Anesth Analg. 1993;76:580–584.

38. Scherer R, Schmutzler M, Giebler R, Erhard J, Stocker L, Kox WJ. Complications related to thoracic epidural

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activity and contractility after upper abdominal surgery. Anesthesiology. 1993;78:63–71.

40. Schnitzler M, Kilbride MJ, Senagore A. Effect of epidural analgesia on colorectal anastomotic healing and

colonic motility. Reg Anaesth. 1992;17:143–147.

41. Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. 2nd ed.

Philadelphia, Pa: JB Lippincott; 1988.

42. Bromage PR. Epidural analgesia. Philadelphia, Pa: WB Saunders; 1978: 443–650.

43. Johnson A, Lofstrom JB. Influence of local anesthetics on ventilation. Reg Anaesth. 1991;16:7–12.

44. Blomberg S, Emanuelsson H, Kvist H, et al. Effects of thoracic epidural anesthesia on coronary arteries and

arterioles in patients with coronary artery disease. Anesthesiology. 1990;73:840–847.

45. Reiz S. Circulatory effects of epidural anesthesia in patients with cardiac disease. Acta Anaesthiol Belg.

1988;39:21–27.

46. Guinard J, Mavrocordatos P, Chiolero R, Carpenter R. A randomized comparison of intravenous versus lumbar

and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology. 1992;77:1108–1115.

47. Sandler AN, Stringer D, Panos L, et al. A randomized double-blind comparison of lumbar epidural and

intravenous fentanyl infusions for postthoracotomy pain relief. Anesthesiology. 1992;77:626–634.

48. Fromme G, Steidl L, Danielson D. Comparison of lumbar and thoracic epidural morphine for relief of

postthoracotomy pain. Anesth Analg. 1985;64:454–455.

49. Hakanson E, Bengtsson M, Rutberg H, Ulrick A. Epidural morphine by the thoracic or lumbar routes in

cholecystectomy. Effect on postoperative pain and respiratory variables. Anaesth Intensive Care. 1989;17:166–169.

50. Boswell MV, Iacono RP, Guthkelch AN. Sites of action of subarachnoid lidocaine and tetracaine: Observations

with evoked potential monitoring during spinal cord stimulator implantation. Reg Anaesth. 1992;17:37–42.

51. Lambert DH, Hurley RJ. Cauda equina syndrome and continuous spinal anesthesia. Anesth Analg. 1991;72:817–

819.

52. Rigler ML, Drasner K, Krejcie TC, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth

Analg. 1991;72:275–281.

53. VanGessel EF, Forster A, Schweizer A, et al. Comparison of hypobaric, hyperbaric, and isobaric solutions of

bupivacaine during continuous spinal anesthesia. Anesth Analg. 1991;72:779–784.

54 Etches R, Sandler A, Daley M. Respiratory depression and spinal opioids. Can J Anaesth.1989;36:165–185.

55. Stoelting R. Intrathecal morphine—an underused combination for postoperative pain management. Anesth

Analg. 1989;68:707–709.

56. Ellis H, ed. Anatomy for Anaesthetists. 6th ed. Oxford, England: Blackwell Scientific Publications; 1993.

57. Hoerster W, ed. Regional Anesthesia. 2nd ed. St Louis, Mo: Mosby–Year Book; 1990.

58. Murphy DF. Intercostal nerve blockade for fractured ribs and postoperative analgesia: Description of a new

technique. Reg Anaesth. 1983;8:151–153.

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60. Kambam J, Hammon J, Parris W, Lupinetti F. Intrapleural analgesia for postthoracotomy pain and blood levels

of bupivacaine following intrapleural injection. Can J Anaesth. 1989;36:106–109.

61. Reiestad F, Stromskag K. Interpleural catheter in the management of postoperative pain. Reg Anaesth. 1986;11:89–91.

62. Rosenburg P, Scheinin B, Lepantalo M, Lindfors O. Continuous intrapleural infusion of bupivacaine for

analgesia after thoracotomy. Anesthesiology. 1987;67:811–813.

63. Stromskag K, Reiestad F, Holmquist E, Ogenstad S. Intrapleural administration of 0.25%, 0.375%, and 0.5%

bupivacaine with epinephrine after cholecystectomy. Anesth Analg. 1988;67:430–434.

64. Murphy DF. Interpleural analgesia. Br J Anaesth. 1933;71:426–434.

65. Lee V, Abram S. Intrapleural administration of bupivacaine for postthoracotomy analgesia. Anesthesiology.

1987;66:586

66. Moore D, Bridenbaugh L. Pneumothorax: Its incidence following intercostal nerve block. JAMA. 1962;

1005–1008.

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Anaesthesiol Scand. 1990;34:1250–1254.

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saturation and length of stay in the postanesthesia care unit. Acta Anaesthesiol Scand. 1990;34:486–491.

69. Ejlersen E, Andersen H, Eliasen K, Mogensen T. A comparison between preincisional and postincisional

lidocaine infiltration and postoperative pain. Anesth Analg. 1992;74:495–498.

70. Barash P, ed. Clinical Anesthesia. Philadelphia, Pa: JB Lippincott; 1989.

71. Bridenbaugh LD. The upper extremity somatic blockade. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade

in Clinical Anesthesia and Management of Pain. 2nd ed. New York, NY: JB Lippincott; 1988: 387–416.

72 Scott B. Techniques of Regional Anaesthesia. Sydney, Australia: Prentice-Hall; 1989.

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Chicago, Ill.

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Chapter 13

PERIOPERATIVE PAIN MANAGEMENT

JOHN M. STAMATOS, M.D.*; BEN H. BOEDEKER, D.V.M., M.D., PH.D.†; AND FRANK D. CROWL, M.D.‡

INTRODUCTION

PATHOPHYSIOLOGY OF PAIN

Local Transmitters of Pain

Transmission of Pain

SECONDARY MANIFESTATIONS OF ACUTE PAIN

Respiratory System

Cardiovascular System

Gastrointestinal and Genitourinary Systems

Endocrine and Metabolic Systems

CLINICAL PHARMACOLOGY OF OPIOID ANALGESICS

Opioid Agonists

Opioid Agonist–Antagonists

Mixed Agonists

Adjunct Medications

CLINICAL PHARMACOLOGY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Mechanisms of Action

Side Effects

CLINICAL PHARMACOLOGY OF LOCAL ANESTHETICS

Chemical and Physical Properties

Mode of Action

Frequency-Dependent Blockade

Receptor Sites in the Sodium Channel

Actions of Local Anesthetics on Nerve Fibers

Pharmacokinetics

Toxicity

SELECTION OF LOCAL ANESTHETICS

Esters

Amides

MODE OF ADMINISTRATION OF ANALGESIC DRUGS

Intramuscular and Intravenous Routes

Epidural and Intrathecal Routes

SUMMARY

*Formerly, Captain, Medical Corps, U.S. Army; Chief, Pain Management Services, Department of Anesthesiology, Walter Reed Army Medical

Center, Washington, D. C. 20307-5001; currently, Associate Director, The New York Center for Pain Management and Rehabilitation, St.

Vincent’s Hospital and Medical Center of New York, 130 West 12th Street, New York, New York 10011

†Major, Medical Corps, U.S. Army; Assistant Professor, Department of Anesthesiology, Uniformed Services University of the Health Sciences,

Bethesda, Maryland 20814-4799; and Assistant Clinical Professor, Pennsylvania State University, College of Medicine, Department of

Anesthesia, Hershey Medical Center, Hershey, Pennsylvania 17033

‡Formerly, Major, Medical Corps, U.S. Army; Department of Anesthesiology, Walter Reed Army Medical Center, Washington, D. C. 20307-

5001; currently, Anesthesia Department, Holy Cross Hospital, 1500 Forest Glen Road, Silver Spring, Maryland 20910
Anesthesia and Perioperative Care of the Combat Casualty

288

INTRODUCTION

Pain control has become an integral part of the

anesthesiologist’s professional responsibilities. The

physiological and humanitarian ramifications of

inadequate pain relief can be catastrophic.

Postinjury pain control in past wars has not always

been optimal; in many instances, there has been

none. Every war has its own descriptions of the

suffering of untreated casualties, and it was the

sound of casualties dying on the battlefield of

Solferino in 1859 that motivated Henri Dunant to

take the first steps that led to the formation of the

International Red Cross:

The stillness of the night was broken by groans, by

stifled sighs of anguish and suffering. Heart-rending voices kept calling for help. Who could ever

describe the agonies of that fearful night!1(p41)

More than humanitarian concerns are relevant to

managing pain, however; postinjury or postoperative pain relief also blunts the trauma-induced neuroendocrine response that leads to detrimental

metabolic, respiratory, and cardiovascular derangements. Thus, effective analgesia can both make the

casualty more comfortable and decrease morbidity.

Although this chapter is oriented toward the

management of pain in postoperative, hospitalized,

combat casualties, military anesthesia providers

need to know not only the full dimensions of providing analgesia to combat casualties but also what

specifically can and should be done in the echelons

below the corps level. The landmark battlefield

study on pain in combat casualties was carried out

by members of the U.S. Army Medical Corps in Italy

in late 1943 and 1944.2 The impetus for this study

came from the observation that, at corps-level hospitals, increasing numbers of casualties were being

seen who had obvious clinical signs and symptoms

of morphine overdose and even lethal poisoning.

This problem was soon shown to be due to the

practice by field medical personnel of injecting

morphine—in 30-mg increments, subcutaneously

or intramuscularly—soon after the casualty had

been wounded. Absorption of the morphine from

the site of injection was sluggish because the weather

was cold and many of the casualties were hypovolemic or even in shock. Thus, repeated doses

were given to relieve pain. On arriving at the

hospital level and with the initiation of resuscitation, the morphine that was deposited in peripheral

tissue was rapidly absorbed into the circulation—

sometimes with fatal results.

By studying the prevalence of pain in combat

casualties, the investigators set about determining

how much morphine was really needed to obtain an

acceptable degree of pain relief. On arriving at the

corps hospital, casualties were asked to describe

their pain, if any, using the following scale: none,

slight, moderate, or severe. Casualties who admitted to pain of any degree were then asked if they

wanted something to relieve it. Two hundred

twenty-five casualties, representative of the more

severely injured, were studied. Of these, 10 were

subsequently excluded because their state of consciousness was altered. The remaining casualties

were stratified into five groups according to the

nature of their wounds: (1) fractures of extremity

bone, (2) extensive soft-tissue injuries, (3) penetrating wounds of thorax, (4) penetrating wounds of

abdomen, and (5) wounds of the head or brain or

both (Figure 13-1 and Table 13-1). Ethical considerations precluded a study design in which one population would serve as an unmedicated control group;

thus, most casualties had received morphine before

reaching the hospital level.

Two striking findings emerged from this study.

When seen at the hospital and evaluated for pain

(7–14 h after their injuries, which was not a remarkably long time by World War II standards, and at

least 5 h after last receiving morphine),

• approximately 75% of the casualties had no

desire for medication for pain relief, and

• approximately 75% of the casualties had no

pain or pain that was slight to moderate in

intensity.

Because the amount of morphine administered

was not different for those with or without pain and

those who did or did not desire an analgesic, the

investigators believed that the intensity of pain

could not be explained on the basis of the amount of

morphine administered. They concluded that

• most combat casualties do not need an analgesic prior to arrival at the hospital level,

with the probable exception of casualties

with abdominal wounds, in whom pain relief would appear to be usually indicated;

and
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289

Degr

Fig. 13-1. When the nature of pain—assessed on admission to third-echelon hospitals—was studied in combat

casualties who were wounded in Italy during World War II, the distribution of pain intensity could be plotted as a

function of wound type. Most casualties with fractures, soft-tissue, and thoracic injuries reported little pain; most

casualties with head wounds reported little or no pain. Only casualties with abdominal wounds demonstrated a great

need for analgesia. Data source: Beecher HK. The control of pain in men wounded in battle. In: DeBakey ME, ed. General

Surgery. Vol 2. In: Coates JB Jr, ed. Surgery in World War II. Washington, DC: US Department of the Army, Medical

Department, Office of The Surgeon General; 1955: 4–49.

TABLE 13-1

EPIDEMIOLOGICAL ASPECTS OF A WORLD WAR II COMBAT CASUALTY PAIN STUDY

Time Since Total Dose of Time Since Last Request Further

Injury (h) Morphine (mg) Dose (h) Pain Relief

Type of Injury (m ± sd) (m ± sd) (m ± sd) (%)

Fractured extremity bone (n = 50) 12.5 ± 1.3 27 ± 1.5 7.0 ± 0.8 22

Extensive soft-tissue extremity

injury (n = 50) 11.4 ± 1.4 27 ± 2.7 7.2 ± 0.6 18

Penetrating, of thorax (n = 50) 9.8 ± 1.0 25.0 ± 1.8 6.5 ± 0.6 20

Penetrating, of abdomen (n = 50) 7.2 ± 0.7 29.0 ± 2.2 4.8 ± 0.7 54

Head and/or brain (n = 15) 7.9 ± 1.4 19.8 ± 4.2 6.2 ± 1.5 7

Adapted from Beecher HK. The control of pain in men wounded in battle. In: DeBakey ME, ed. General Surgery. Vol 2. In: Coates JB Jr, ed.

Surgery in World War II. Washington, DC: US Department of the Army, Medical Department, Office of The Surgeon General; 1955: 45.

• if morphine is required, it should be administered intravenously (which, of course, may

not be practicable on the battlefield).

At the hospital level and especially following

surgical intervention, a patient’s degree of pain is

often difficult to assess. The recovery room

personnel’s assessment of the casualty’s pain is

usually subjective. A patient’s communication skills

and cultural background will influence the ability

to express his or her level of discomfort. Several

pain scores have been developed to help eliminate

None

Slight

Moderate

Severe

Type of Injury

15

Fracture Soft Tissue Thorax Abdomen Head/Brain

10

5

0

20

25

Number of Casualties
Anesthesia and Perioperative Care of the Combat Casualty

290

the subjectivity in the assessment of acute pain, but

these are much more useful in a research setting or

a civilian hospital than on the battlefield.3

Fortunately for casualties of modern warfare,

many techniques and drugs are now available that

provide considerable analgesia. Some, such as patient-controlled analgesia (PCA), will allow the casualty more autonomy with respect to narcotics

administration, which will simultaneously reduce

the demand for nursing care.4,5 Administration of

narcotics by the epidural or intrathecal routes will

provide sustained pain relief far beyond that obtained with the more traditional intramuscular or

intravenous routes.6 By employing dilute concentrations of local anesthetics, regional blocks can be

used to provide pain relief with a minimal decrement of motor function.7 New nonsteroidal

antiinflammatory drugs (NSAIDs), which are nearly

as effective as the narcotics used in prior wars but

are not addictive, can be given intramuscularly or

intravenously and act as an adjunct in the therapy

of the injured soldier.8 By taking advantage of the

newer techniques, military anesthesiologists can

help soldiers who are injured on the battlefield to

recover from surgery with minimal—or at least

greatly reduced—discomfort.

Military trauma anesthesiologists must be able to

meet the soldiers’ postoperative pain requirements,

have a sound working knowledge of the drugs at

our disposal, and be adept in the use of the different

modes of delivery and administration. The battlefield is not the ideal setting in which to treat patients. Therefore, we must be able to adapt to the

situation and adequately treat the casualties as they

present, using innovative ideas and combinations

of treatment modalities to care for these soldiers.

PATHOPHYSIOLOGY OF PAIN

Visceral pain originates from organs of the abdominal cavity and thorax. The receptors cover

large areas and the impulses travel through unmyelinated sympathetic fibers. These nerves respond

to stretch, crush, ischemia, and displacement. The

pain generated from these areas is dull, aching, and

difficult to localize. The normal causes of visceral

pain are distention of the viscera or renal pelvis

secondary to obstruction. Somatic pain, in contrast,

is transmitted in unmyelinated C fibers and small,

myelinated, A-delta fibers, the impulse arising in

receptors in skin, fasciae, bones, and joint spaces.

These receptors innervate small discrete areas and

are able to pinpoint noxious stimuli. Myelinated

somatic nerve fibers, which are called A fibers, are

the largest in diameter and conduct impulses the

most rapidly. A fibers are further divided, by their

progressively decreasing sizes, into alpha, beta,

gamma, and delta fibers. The alpha and beta fibers

convey motor and proprioception information. The

gamma fibers control muscle spindle tone. The

delta fibers, which are the A fibers with the smallest

diameter, transmit messages concerning pain, temperature, and touch (Table 13-2).9

The thinly myelinated B fibers are smaller than

the alpha fibers and have a preganglionic autonomic function for both sympathetic and parasympathetic systems.9 The unmyelinated C fibers are

the smallest diameter nerve fibers. They have the

lowest rate of impulse conduction velocity and contain postganglionic autonomic axons as well as axons

conveying pain, temperature and touch information.10

Three major types of receptors are stimulated by

nociceptive input: low-threshold mechanoreceptors,

high-threshold mechanoreceptors, and polymodal

nociceptors. Low-threshold mechanoreceptors respond to mechanical stimulation like pressure.

These receptors are carried on A-delta fibers and

transmit the stimuli at about 20 m/s.11 As the input

increases, the firing rate increases. High-threshold

mechanoreceptors respond to noxious mechanical

stimulation. As they are on low-threshold mechanoreceptors, impulses to high-threshold mechanoreceptors are carried on A-delta fibers. Polymodal

nociceptors transmit impulses through unmyelinated C fibers. These receptors respond to many

different kinds of nociceptive input including chemical, thermal, and mechanical. The receptive fields

are larger than those of the A-delta fibers, and

stimulation of these fibers lasts longer than with the

other receptors.12 The generally accepted paradigm

for pain perception, modulators, and transmitters is

shown in Figure 13-2.

Local Transmitters of Pain

The many different biochemical transmitters of

pain include potassium and hydrogen ions, serotonin, histamine, bradykinin, substance P, and

leukotrienes.13 When injected locally, all these substances either (a) are responsible for the transmission of noxious stimulation or (b) decrease the threshold of the pain transmission.14

Both potassium and hydrogen ions sensitize nerve

endings and are usually released from cells when
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291

TABLE 13-2

CLASSIFICATION OF NERVE FIBERS

Diameter Conduction

Fiber Type (μm) Rate (m/s) Anatomical Location Function

A

Alpha 12–20 100 Afferent to and efferent from muscles Large motor and proprioception

and joints

Beta 5–12 30–85 Afferent to and efferent from muscles Small motor, muscle tone, touch,

and joints pressure

Gamma 3–6 15–35 Efferent to muscle spindles Muscle tone

Delta 2–5 3–25 Sensory roots and afferent peripheral Sharp pain, temperature, touch

nerves

B

3 3–15 Preganglionic autonomic Vasomotor

Visceromotor

Suromotor

Pilomotor

C

sC 0.3–1.3 0.7–1.3 Postganglionic sympathetic Vasomotor

Visceromotor

Suromotor

Pilomotor

drC 0.4–1.2 0.1–2.0 Sensory roots and afferent peripheral Dull pain

nerves Temperature

Touch

Data sources: (1) Raj P. Practical Management of Pain. 2nd ed. St. Louis, Mo: Mosby–Year Book; 1992: 139. (2) Barash PG, Cullen BF,

Stoelting RK, eds. Clinical Anesthesia. Philadelphia, Pa: JB Lippincott; 1989: 374.

they are damaged during injury. Activity of peripheral pain receptors are regulated by, among

other substances, serotonin and histamine. Serotonin is also a neurotransmitter for the descending

inhibitory pathways. Bradykinin, a 9–amino acid

peptide, is produced by enzymatic activity at the

site of cell breakdown. Binding sites for bradykinins have also been found in the dorsal columns.

Substance P, an 11–amino acid peptide, is synthesized in the dorsal root ganglia, from where it is

transferred both centrally and peripherally along

the nerve. In the peripheral locale—a nerve ending—substance P activates an enzyme that catalyzes the formation of arachidonic acid, which, in

turn, serves as the substrate of the enzyme

cyclooxygenase. This results in the production of

prostaglandin E2, an eicosanoid, that not only increases the sensitivity of nerve endings to chemical

agents and mechanical injuries but also, by itself,

causes hyperalgesia.15 Substance P is also indirectly

responsible for the vasodilation associated with

local injury.16 The leukotrienes are also derivatives

of arachidonic acid, but that reaction is catalyzed by

lipoxygenase. There are many different leukotrienes, and most are associated with lowering the

threshold of the nerves associated with the transmission of pain.

Transmission of Pain

The events leading to the transmission of pain

were first reported in 1927 and described as a triple

response: intense vasodilation, local edema or

wheal, and secondary vasodilation spreading to

the local area.17 This response is mediated by the

transmitters of pain and stimulates the nociceptor

fibers to fire. These fibers then synapse in the

dorsal column of the spinal cord. There, the impulses are modulated and transmitted to the contralateral spinothalamic tract up into the cerebral

cortex. The spinothalamic tract is subdivided into

subtracts, one of which, the lateral subtract (found
Anesthesia and Perioperative Care of the Combat Casualty

292

Fig. 13-2. Pain perception depends on the integrated function of three neurological pathways. First, peripheral nerves

connect pain receptors in the injured tissue with neurons in the dorsal horn of the spinal cord. Second, nerve fibers pass

from the dorsal horn neurons to the contralateral side of the cord, where they ascend to the cerebral cortex. The third

component consists of tracts that arise in the upper brain stem and descend to the dorsal horn neurons, the function

of which is thereby modulated. The ascending tract also has a component that passes to the limbic system and no doubt

is important in modifying the emotional response to pain. A large number of transmitters are believed to be important

in transmitting information about pain; several of these are discussed in text. GABA: γ-aminobutyric acid; VIP:

vasoactive intestinal polypeptide; CCK-8: cholecystokinin-8. Reprinted with permission from Kehlet H. Postoperative

pain. In: Wilmore DW, Brennan MF, Harken AH, Holcroft JW, Meakins JL, eds. Critical Care. Vol 1. In: American College

of Surgeons: Care of the Surgical Patient. New York, NY: Scientific American, Inc; 1988–1993: II-12-10.

only in advanced primates), is probably responsible

for the pinpoint perception of traumatic injury. As

the impulses travel to the sensory tract of the cerebral cortex, they pass through the thalamus where

they are again modulated. Once in the sensory

cortex, the painful impulse is perceived and the

body’s response is determined. Thus, the major

areas of the body in which pain is modulated are the

dorsal columns, the spinothalamic tract, the thalamus, and the sensory cortex. The treatment of pain

needs to focus on these areas.

Descending inhibitory pathways originate in the

sensory cortex and terminate in the dorsal horn.

These pathways are responsible for down-regulation of painful stimuli by releasing serotonin, norepinephrine, and enkephalins, which inhibit the ac-
Perioperative Pain Management

293

rally occurring endorphins and enkephalins) activate both of the descending inhibitory pathways

and bind presynaptically to the opioid receptors of

the neurons in the dorsal horn. Opioids act to

reduce the amount of substance P present.20 Local

anesthetics work by blocking the axonal transmission of pain.21 Antipsychotics work to increase the

level of serotonin in the dorsal horn and thus downregulate the pain transmissions.22 NSAIDs stop the

production of prostaglandin E2 from prostacyclin.23

Alpha-2 adrenergic agonists inhibit substance P by

stimulating presynaptic and postsynaptic spinal

cord receptors, which, in turn, inhibit pain transmission with a mechanism of action that is different

from that of narcotics.24

tivity of neurons that give rise to the fibers found in

the spinothalamic tract. The release of substance P

also causes the release of vasoactive substances

(serotonin, bradykinin, histamine) at the site of

injury. These substances stimulate both a hyperemic

response and a hyperalgesic state at the injured site.

Prostaglandins that are present in the cell membranes are also released in response to noxious

stimuli. These substances do not themselves cause

pain, but they do potentiate the noxious effects of

the other substances that are present.18

The pharmacological treatment of pain is targeted to work on these sites of action. Opioids (ie,

any natural or synthetic drug that has morphinelike

pharmacological properties,19 including the natuSECONDARY MANIFESTATIONS OF ACUTE PAIN

The rationale for relieving pain transcends the

anesthesiologist’s professional mandate to alleviate suffering. Pain by itself has many deleterious

effects, of which the inability to rest and sleep are the

most obvious. Less obvious but of greater medical

importance are such effects as pain-induced spasm of

injured muscle, especially splinting of respiratory

muscles; reflex stimulation of the autonomic nervous system, which causes hypertension and the

release of catabolic hormones; and inhibition of the

normal functions of the gut and urinary tract.

Respiratory System

The respiratory system is most often affected in

injuries to the thoracic region or the upper abdomen. Casualties who remain in pain postoperatively splint when trying to breathe. This can cause

decreased lung volumes and atelectasis, and can

progress to lung collapse and pneumonia. The

recognition of the importance of relieving pain in

casualties with thoracic trauma was one of the most

important advances in thoracic surgery during

World War II:

[P]ain was an almost constant accompaniment of

any wound of the chest. The relief of pain had a

vital bearing on hastening recovery.... [U]ntil it

had been accomplished, the patient was unwilling

to breathe deeply or cough, because of the discomfort which followed both acts, and fluid substances

therefore accumulated in the tracheobronchial tree,

which led to wet lung.25(p244)

Similar observations regarding pain in thoracic surgery have been made in civilian practice; pulmonary function greatly improves when adequate analgesia is provided.26

Cardiovascular System

Pain causes the amount of circulating catecholamines to increase. The effects of catecholamines on

the cardiovascular system include increased (a) heart

rate, (b) blood pressure, (c) cardiac output, and (d)

systemic vascular resistance. Taken by itself, the

increased heart rate, by limiting the time available

for diastolic flow to occur, will cause a decrease in

coronary blood flow. The usual concomitant increase in arterial pressure and coronary vasodilation caused by a catechol-mediated increase in

cardiac metabolism negate the isolated effect of

heart rate. Thus, coronary flow increases during

tachycardia. Cardiac output may or may not change,

depending on peripheral impedance. Increased

systemic resistance will cause an increase in the

workload for the heart. Together, these factors lead

to increased myocardial oxygen consumption and,

therefore, to an increased risk of myocardial ischemia

in patients with limited cardiac reserve.27 However,

due to their age and physical condition, most injured soldiers should be able to tolerate this hemodynamic stress.

Gastrointestinal and Genitourinary Systems

Untreated pain will lead to decreased gastrointestinal motility with associated anorexia, nausea, and

vomiting.28 This places the patient at increased risk

of pulmonary aspiration, and anastomotic and

incisional dehiscence, and complicates the manage-
Anesthesia and Perioperative Care of the Combat Casualty

294

TABLE 13-3

NEUROENDOCRINE AND METABOLIC RESPONSES TO TRAUMA

Response Effect Cause

Endocrine Catabolic Increased ACTH, cortisol, ADH, GH, catecholamines, renin, angiotensin II, aldosterone,

glucagon, interleukin-1

Anabolic Decreased insulin, testosterone

Metabolic

Carbohydrate Hyperglycemia, glucose intolerance, Increased hepatic glycogenolysis

insulin resistance (epinephrine, glucagon)

Increased hepatic gluconeogenesis (cortisol,

glucagon, growth hormone, epinephrine,

free fatty acids)

Decreased insulin secretion/action

Protein Muscle protein catabolism, increased Increased cortisol, epinephrine, glucagon,

synthesis of acute-phase proteins interleukin-1

Fat Increased lipolysis and oxidation Increased catecholamines, cortisol, glucagon,

growth hormone

Water and Electrolyte Flux Retention of H2O and Na+, increased Increased catecholamines, aldosterone, ADH,

excretion of K+, decreased functional cortisol, angiotensin II, prostaglandins,

extracellular fluid with shifts to and other factors

intracellular compartments

ACTH: adrenocorticotropic hormone; ADH: antidiuretic hormone; GH: growth hormone. Adapted with permission from Cousins

M. Acute and postoperative pain. In: Wall PD, Melzac R. Textbook of Pain. New York, NY: Churchill Livingstone; 1989: Chap 18: 294.

ment of the casualty who needs to be returned to the

operating room for additional surgery. Furthermore, sluggish gastrointestinal function delays the

resumption of enteral nutrition. Unrelieved pain

has a similar effect on the function of the urinary

tract: persistent bladder retention necessitating prolonged urinary catheterization.

Endocrine and Metabolic Systems

Increased pain causes a stress response that manifests as an increase in the release of endogenous

catecholamines, cortisol, and other mediators of the

sympathetic response that promote harmful protein catabolism, glucose intolerance, and insulin

resistance.29

An all-inclusive review of the endocrine response

to postoperative pain is not within the scope of this

chapter. Suffice it to say that the endocrine response to trauma—whether surgical or otherwise—

is profound. Every system in the body is affected by

these changes, most of which are secondary to circulating catecholamines released from the sympathetic nervous system (Table 13-3). Anabolism,

catabolism, and substrate requirements all increase.

The dual goals of postoperative pain control are the

alleviation of pain and the subsequent decrease in

the levels of circulating catecholamines.

CLINICAL PHARMACOLOGY OF OPIOID ANALGESICS

The opioids, of which morphine is the prototype,

are the best known and most useful narcotic analgesics available. Morphine was first isolated from

opium—the gum obtained by drying the milky juice

made from the seedpod of the poppy plant Papaver

somniferum—in 1803.19

Opioids act at two distinct anatomical sites: the

supraspinal area and the spinal cord. In the

supraspinal area, the drugs bind at receptor sites in

the periventricular and periaqueductal gray area to

modulate pain perception. In the spinal cord, the

action is in the substantia gelatinosa of the dorsal
Perioperative Pain Management

295

horn. Here, the drugs block the release of the

mediators of pain by binding to presynaptic receptors of afferent nerve terminals.20

Whether synthetic or derived from opium, these

drugs are described by their effects at specific opioid

receptors in the central nervous system (CNS). Four

distinct opioid receptors have been identified in

humans: mu, delta, kappa, and sigma.

The mu receptors are further subdivided into mu

1 and mu 2. Mu 1 receptors are located in the spinal

cord and in the supraspinal area. Stimulation of

these receptors produces analgesia. Morphine and

beta-endorphin are agonists for this receptor. Mu 2

receptors cause ventilatory depression, decreased

heart rate, euphoria, miosis, and physical dependence. Agonists of this group include fentanyl and

meperidine.

The delta receptors, which have no intrinsic function, function as modulators of the mu receptors.

Leuenkephalin is an agonist in this group.

The kappa receptors are located in the cerebral

cortex and their activation causes analgesia, sedation, miosis, and some depression of ventilation.

Agonists of this group include nalbuphine and

butorphanol.

The sigma receptors are the latest of the opioid

receptors to be described. Activation of this receptor stimulates dysphoria, tachycardia, and tachypnea. This may be the site of ketamine’s action.

Naloxone is an antagonist for all the opioid receptors.30

Opioid Agonists

Morphine

HO

O

N CH3

HO

2

3

4

5

6 8

9

10

11

12

13

15 16

1

7

14

morphine

An opioid agonist, morphine has demonstrated

mu 1 activity in the periaqueductal gray matter.

These receptors modulate noxious stimuli and send

transmissions to the medullary nuclei. Spinal mu

receptors also reduce the amount of substance P in

the dorsal horn.

Morphine can be administered via the intravenous, intramuscular, epidural, and intrathecal

routes. When delivered intravenously, morphine

has a peak effect about 20 minutes after injection.

Intramuscularly, an initial effect is seen in 15 to 30

minutes and the peak effect in 45 to 90 minutes.

Orally administered morphine is not reliably absorbed. When given epidurally, the onset of pain

relief tends to occur approximately 60 minutes later,

and pain relief can last 16 to 24 hours. With

intrathecal injections, the onset of pain relief tends

to occur in approximately 10 to 15 minutes, which

coincides with the peak level of drug in the cerebrospinal fluid.30 Regardless of the mode of administration, the pain relief is relative to the concentration of the drug in the cerebrospinal fluid; pain

relief is not always proportional to the blood levels.31 The drug is eliminated from the body primarily by conjugation with glucuronic acid at hepatic

and extrahepatic sites. A small amount of the dose

is excreted unchanged in urine. Only 7% to 10% of

morphine is eliminated by biliary excretion; the rest

is excreted by the kidneys.30

Respiratory Side Effects. Mu 2 receptors in the

pontine and medullary centers are responsible for

respiratory depression.32 The agonists produce a

dose-related depression of respiration, the evidence

of which is increased PaCO2. When morphine is

administered in small doses, the respiratory rate

usually decreases, which is compensated for by an

increase in the tidal volume. With increasing doses

of morphine, however, the tidal volume will decrease. Maximal respiratory depression occurs approximately 7 minutes after intravenous administration, 30 minutes after intramuscular injection, 90

minutes after subcutaneous administration, and up

to 16 hours after epidural or intrathecal administration.30

Cardiovascular Side Effects. Morphine administration will decrease sympathetic outflow. No adverse effect will probably be seen in a supine,

normovolemic patient, but a casualty who is standing or a supine casualty who is hypovolemic might

suffer from hypotension. Morphine can also stimulate histamine release, causing peripheral vasodilation and hypotension. The histamine release can be

attenuated by limiting the rate of infusion to less

than 5 mg/min or by administering H1 or H2 blockMorphine, the major phenanthrene alkaloid of

opium, and codeine are the medically useful opioids derived from opium. Although codeine can be

administered orally, it is not as potent as morphine

and therefore will not be further discussed in this

chapter.
Anesthesia and Perioperative Care of the Combat Casualty

296

C

H2 H2

C N N C

O

C2H5

fentenyl

ing agents.33 Morphine can also cause bradycardia,

probably by stimulating the vagal nuclei in the

medulla, and by exerting a depressing effect on the

sinoatrial node. Although there are no known direct myocardial depressant effects of morphine, it

causes a decrease in myocardial oxygen consumption. The mechanism is probably related to peripheral vasodilation and bradycardia. There is no

direct effect on the cerebral circulation, but the

secondary effect of the increased PaCO2 due to associated hypoventilation will cause cerebral vasodilation that could thereby increase intracranial pressure in the patient with neurotrauma.

Gastrointestinal Side Effects. Pain may cause

decreased gastric emptying and motility. Morphine may enhance this dysmotility and lead to

ileus. In addition, the tone of the ileocecal and anal

sphincters is also increased. All these factors lead to

decreased motility of and increased water absorption from the gut. Opioids will also cause spasm in

the biliary smooth muscle (eg, the sphincter of Oddi).

This spasm may mimic the pain of angina pectoris.

Nausea and vomiting are caused by direct stimulation of the chemoreceptor trigger zone of the

medulla oblongata. This side effect can be treated

with an antiemetic without reversing the analgesic

effect of the morphine.

Genitourinary Side Effects. Morphine will cause

increased peristalsis of the ureters, but the tone of

the vesicle sphincter is also increased. The combination of these effects makes it more difficult for

patients who are not catheterized to urinate. In

some patients, morphine may also inhibit the urge

to urinate.

Cutaneous Side Effects. Morphine will cause

venodilation in the peripheral vessels of the extremities. The histamine release can also cause an

erythema.

Pruritus, which is more pronounced in epidural

and intrathecal use, can be pronounced and is secondary to a CNS effect of the drug. Pruritus can be

reversed by titrating small amounts of an antagonist (eg, naloxone).30

Physical Dependence. All opioids can cause

physical dependence. This complication occurs

more often with agonists than with drugs that have

combined agonist–antagonist effects. Although it

usually takes longer, dependence can occur after as

few as 72 hours of use. However, the possibility of

dependence should not be a factor in limiting the

use of a narcotic in the acutely injured soldier.

Dosage and Administration. For postoperative

pain control, morphine should be titrated for effect.

For intravenous or intramuscular injections, 0.05 to

0.1 mg/kg should provide adequate analgesia.

Following this dose, the patient should be monitored for adequacy of pain control, changes in blood

pressure and pulse, and respiratory rate. If the

patient’s pain is not controlled, then more narcotic

can be administered; again, the patient’s vital signs

should be observed. When used intravenously or

intramuscularly, morphine should be given every 3

to 6 hours.34 Strict adherence to dosing intervals is

needed to maintain therapeutic drug levels.

Epidurally or intrathecally administered morphine can provide pain relief for 16 to 24 hours with

a single dose. It is important to remember that

morphine’s respiratory depression might not manifest itself for up to 20 hours after an injection. For

acute pain, the doses of epidural morphine are 0.05

to 0.07 mg/kg, and can be administered every 12

hours as needed.35 The anesthesiologist must bear

in mind that morphine delivered via the epidural

route requires up to 1 hour before the onset of pain

relief. Morphine can be continuously infused at a

rate of 0.005 to 0.01 mg/kg/h. Intrathecal narcotics

also have the benefit of extended pain relief from a

single injection. The usual dose of intrathecal morphine is 0.3 to 1 mg. The onset of action is almost

immediate and the duration of a single injection is

12 to 24 hours.6,35–37

Fentanyl

The opioid fentanyl is chemically similar to morphine. However, this synthetic narcotic is 75- to

125-fold more potent than morphine and, due to its

high lipid solubility, it crosses the blood–brain barrier faster than morphine. The onset of action is

approximately 30 seconds. The duration of action

of the drug is also shorter than that of morphine,

owing to fentanyl’s rapid uptake by inactive tissue.

Because of this uptake and subsequent release, when

fentanyl has been given in repeated doses, its action

can continue and be prolonged after the medication

has been discontinued.38 Fentanyl is metabolized

by dealkylation, hydroxylation, and amide hydrolysis into inactive metabolites. The drug is excreted in

the urine and feces.
Perioperative Pain Management

297

N CH3

H5C2 O C

O

meperdine

Side Effects. The side effects of fentanyl are

similar to those of morphine. Of note, less histamine is released than with morphine, but there is

greater potential for physical dependence. Muscular rigidity, specifically of the chest wall, has also

been associated with rapidly administered doses of

fentanyl.30

Dosage and Administration. For the postoperative patient with acute pain, 1 to 2 μg/kg of fentanyl

will give fast relief. Fentanyl’s advantage over

morphine is its speed of onset. However, the pain

relief will not last as long as that from a dose of

morphine, and fentanyl probably is not the best

medication if prolonged use of intermittent boluses

is anticipated. However, fentanyl can be given as an

intravenous infusion to maintain pain relief. A

starting dose of 1 to 2 μg/kg/h is adequate, but can

be titrated as necessary.30 Epidural administration

of fentanyl is another useful option. A single injection of 1 to 2 μg/kg in the lumbar epidural space

will give excellent relief from pain that originates in

the abdomen or lower extremities. Long-term relief

can be achieved with 10 μg/mL of fentanyl infusing

at a rate of 1 to 2 μg/kg/h.39,40 As with epidural

administration of morphine, the patient’s respiratory rate must be monitored throughout the duration of infusion, although the delayed respiratory

depression seen with morphine has not been demonstrated with fentanyl. Intrathecal fentanyl can

also be used for pain from the abdomen and lower

extremities. A dose of 0.1 to 0.2 μg/kg is adequate.

The risk for respiratory depression lasts approximately 4 hours—approximately as long as the pain

relief from a single dose.39,40

Meperidine

Although it is structurally different from morphine, meperidine has many of the same properties.

Meperidine is approximately one tenth the strength

of morphine when given as an intravenous or intramuscular injection, but is much better absorbed by

the gastrointestinal system. Analgesic effects are

noted approximately 15 minutes after an oral dose

and 10 minutes after an intramuscular injection.

The peak effect is usually seen within 2 hours after

oral administration and 1 hour after an intramuscular injection. The effective length of analgesia is 2 to

4 hours. Meperidine is metabolized in the liver to

normeperidine. The accumulation of the normeperidine is associated with increased CNS excitation.

In large or frequently repeated doses, meperidine

has caused seizures in humans. Normeperidine is

excreted renally and will accumulate in patients

with renal failure.30

Side Effects. Meperidine’s side effects, like

fentanyl’s, are similar to morphine’s, but with some

differences. Large doses exert a myocardial depressant effect that will decrease myocardial contractility and stroke volume. This will lead to increased

left ventricular filling pressures.41 The incidence of

nausea and vomiting associated with meperidine is

equivalent to that of morphine, but patients who

experience nausea and vomiting with morphine

might not with meperidine.

Dosage and Administration. As mentioned

above, meperidine is approximately one tenth as

potent as morphine when given by intravenous or

intramuscular injection. Thus, for acute post-operative pain relief, a starting dose of 0.25 to 0.5 mg/

kg should be adequate. Also, owing to meperidine’s

better absorption, it is a good choice as an oral

adjunct. The possibility for seizures exists with

prolonged or high-dosage oral use of meperidine.30

Opioid Agonist–Antagonists

Butorphanol

Butorphanol exerts its analgesic effect by being

an agonist of both the kappa and sigma receptors.

It is an antagonist of the mu receptors. A dose of 2

to 3 mg is equipotent to 10 mg of morphine. The

onset, peak effect, and duration of action of

butorphanol are similar to those of morphine. Therapeutic dosages produce increased pulmonary artery pressure, cardiac output, and systemic blood

pressure.34

Side Effects. In the low-dose, therapeutic range,

the respiratory side effects of butorphanol are similar to those of morphine. The cardiovascular effects

are the same as those described for meperidine. The

drug will cause sedation, nausea, and diaphoresis

in most people, and dysphoria in a small number of

patients. Butorphanol will also antagonize mu agonists, thus making the choice of the proper dose of

agonists difficult in the patient who is receiving

butorphanol and will be returning to the operating

room.
Anesthesia and Perioperative Care of the Combat Casualty

298

Dosage and Administration. Butorphanol is not

available for enteral use. The suggested intravenous dose is 7 to 15 μg/kg, and the suggested

intramuscular dose is 15 to 30 μg/kg. Butorphanol

should be readministered every 3 to 4 hours.34

Nalbuphine

Nalbuphine is an agonist at the kappa and sigma

receptors and an antagonist at the mu receptors. A

dose of 10 mg of nalbuphine is equipotent to 10 mg

of morphine. Unlike butorphanol, nalbuphine

does not increase cardiac output or blood pressure.

One advantage of this drug is its ceiling effect on

respiratory depression42: the dose-related decrease

in respiratory drive will not worsen with doses

greater than 30 mg. Also, because nalbuphine is a

mu antagonist, the drug can be used to reverse the

respiratory depression of morphine or fentanyl without decreasing analgesia. The onset, peak effect,

and duration of action are similar to those of morphine.

For postoperative pain relief, nalbuphine should

be titrated for effect. For intravenous or intramuscular injections, 0.05 to 0.1 mg/kg should provide

adequate analgesia. Whether administered via the

intravenous or intramuscular route, nalbuphine

should be given every 3 to 6 hours for pain control.30

Mixed Agonists

Dezocine

Dezocine is a new, mixed agonist with activity at

the mu, kappa, and delta receptors. Its affinity for

the mu receptors is 10-fold greater than for the delta

receptors, and 40-fold greater than for the kappa

receptors. This drug’s advantage over other opioids is its ceiling effect on respiratory depression.

Additionally, it is not a scheduled drug (ie, a federal

narcotics license is not required). Its physical dependence has not been described. The hemodynamic effects are equivalent to those of morphine.

The onset, peak effect, and duration of action are

also similar to those of morphine.43 Minimal side

effects have been found in the clinical studies so far

reported, but the number of patients reported is small.

The recommended dose for dezocine is 70 to 150

μg/kg intravenously and 70 to 200 μg/kg intramuscularly. It is suggested that dezocine be readministered every 3 to 4 hours.43

Naloxone

Naloxone is a competitive inhibitor of the mu,

delta, kappa, and sigma receptors. After an intravenous injection, the onset of action is 1 to 2 minutes.

The duration of action is 1 to 4 hours but is dose

dependent. Naloxone can reverse the effects of all

opioid agonists. It can also cause increased heart

rate and systolic blood pressure. Acute pulmonary

edema has been associated with narcotic reversal

with naloxone, although this is a relatively rare

complication. The case reports of pulmonary edema

following naloxone administration have been in

young healthy patients, and the reported doses

have been as low as 80 μg.44,45

The recommended dose is 0.5 to 1 μg/kg, with

doses being repeated until the desired effect is

achieved. If the opioid being reversed has a longer

half-life than naloxone, then it is important to start

a naloxone infusion. The recommended rate of

infusion is 5 to 10 μg/kg/h, but this rate can be

titrated for effect.46,47

Adjunct Medications

Promethazine is an H1 receptor antagonist that

has been used in conjunction with narcotics to reduce the narcotic-associated nausea. The recommended dose to control nausea in patients is 12.5 to

25 mg every 4 to 6 hours. The dose is given as an

intramuscular injection.

Droperidol is a powerful antiemetic owing to its

inhibition of the dopaminergic receptors in the

chemoreceptor trigger zone of the medulla. A dose

of 0.625 to 1.25 mg given to a 70-kg adult is considered adequate to prevent nausea. Side effects of the

drug include drowsiness and, in a small number of

patients, extrapyramidal reactions. Droperidol may

also cause increased sedation in the patient emerging from anesthesia.

CLINICAL PHARMACOLOGY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Nonsteroidal antiinflammatory drugs (NSAIDs)

act by interrupting the inflammatory response.48

This interruption is thought to be due to their inhibition of prostaglandin biosynthesis. Aspirin (acetylsalicylic acid) is the prototype of the nonopioid

analgesic, antipyretic, and antiinflammatory

drugs.49

NSAIDs are most often used
Perioperative Pain Management

299

Generic Name Trade Name Common Adult Dose for Pain

Salicylates

Aspirin 325–650 mg/4 h PO

Choline/magnesium trisalicylate Trilisate 1,000 mg, PO bid

Diflunisal Dolobid 500 mg PO q 12 h

Salsalate Disalcid 3,000 mg/d total dose divided as tid or bid

Propionic Acid Derivatives

Fenoprofen Nalfon) 200 mg qid or tid

Flurbiprofen Ansaid 200–300 mg total daily dose divided bid, tid, or qid

Ibuprofen Advil, Medipren, 300–800 mg tid to qid PO

Midol, Nuprin,

Motrin

Ketoprofen Orudis 25–50 mg tid to qid PO

Naproxen Naprosyn 250 mg tid to qid PO

Naproxen sodium Anaprox 275 mg tid to qid

Indoles/Pyrroles

Indomethacin Indocin 25–50 mg bid to tid

Sulindac Clinoril 150 mg bid

Tolmetin Tolectin 400 mg tid

Ketorolac Toradol 30–60 mg IM loading dose, then 15–30 mg IM qid

Oxicams

Piroxicam Feldene 20 mg qid

Anthranilic Acid Derivatives

Meclofenamate sodium Meclomen 50 mg tid to qid

Mefenamic acid Ponstel 250 mg qid

Phenylacetic Acid Derivatives

Diclofenac sodium Voltaren 50 mg tid or qid or 75 mg bid

Pyrazolone Derivatives

Phenylbutazone Butazolidin 100 mg qid

TABLE 13-4

SPECIFIC NONSTEROIDAL ANTIINFLAMMATORY AGENTS BY CLASS

• as analgesics, to provide symptomatic relief

of low-intensity pain associated with headache and musculoskeletal disorders (eg,

osteoarthritis and rheumatoid arthritis),

• as antipyretics,

• to inhibit platelet aggregation in patients

vulnerable to vascular obstruction from

emboli,

• to inhibit synthesis of prostaglandins in neonates to evoke closure of the ductus arteriosus, and

• to treat excessive production of prostaglandins (eg, in Bartter’s syndrome).49

Important information regarding generic names,

trade names, and adult dosages of selected NSAIDs

is summarized in Table 13-4; pharmacokinetic data

are presented in Table 13-5.

IM: intramuscularly; PO: by mouth; bid: twice daily; tid: three times daily; qid: four times daily

Data sources: (1) Physicians’ Desk Reference. 48th ed. Montvale, NJ: Medical Economics Data; 1994. (2) DiGregorio G. Handbook of Pain

Management. 3rd ed. West Chester, Pa: Medical Surveillance Inc; 1991.
Anesthesia and Perioperative Care of the Combat Casualty

300

TABLE 13-5

PHARMACOKINETIC DATA OF SELECTED NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Time to Peak Plasma Elimination Duration of Effective Plasma

Name Concentration (h) Half-life (h) Action (h) Concentration (μg/mL)

Aspirin 0.5–1 0.25–0.35 4–6 20

Choline/magnesium 1–2 9–17 12 150–300

Ibuprofen 1–2 2 4–6 —*

Indomethacin 2 2–3 4–6 0.3–1.0

Ketorolac 0.5 4–6 4–6 —

Sulindac 2 7–18 8–12 —

Piroxicam 3–5 30–80 48–72 1.5–2

Meclofenamate sodium 0.5–1 2 2 —

Diclofenac sodium 1–4 2 2 1–2

Phenylbutazone 1–3 60–100 80 50–150

Naproxen 1–2 10–17 8–12 25–75

*[—] Indicates data not available

Adapted with permission from Digregorio GJ, Barbieri EJ, Sterling GH, Camp JF, Prout MF. Handbook of Pain Management. 3rd ed.

West Chester, Pa: Medical Surveillance Inc; 1991: 129.

Mechanisms of Action

The primary actions of NSAIDs—producing analgesia, acting as an antipyretic, and exerting an

antiinflammatory effect—result from different

mechanisms. These actions and mechanisms are

discussed below.

Analgesia

NSAIDs produce analgesia by inhibiting the activity of cyclooxygenase (prostaglandin synthetase),

an enzyme that leads to a decrease in the synthesis

and release of prostaglandins from cells. Individual classes of NSAIDs have different methods of

inhibiting the cyclooxygenase enzyme.49 Prostaglandins enhance the potency of algesic substances

such as bradykinin or substance P, which may stimulate nerve endings of unmyelinated C fibers and

small-diameter A-delta fibers to elicit noxious afferent input. Bradykinin stimulates formation and

release of more prostaglandins.50 NSAIDs appear

to reduce this potentiation of algesic activity of

prostaglandins by blocking their synthesis.

In contrast to that produced by opioids, which

act centrally, the analgesia produced by aspirinlike

drugs is a peripheral phenomenon. Pain is produced when prostaglandins are produced locally

around sensitive nerve endings, as seen with inflammation. NSAIDs are effective in relieving this

pain by blocking prostaglandin synthesis. NSAIDs

are not effective as analgesics when inflammation is

not present (ie, there is no increase in prostaglandin

synthesis in the area) or for the sharp, stabbing pain

that is caused by direct stimulation of sensory nerves

(ie, visceral pain).49

Antipyresis

NSAIDs exert an antipyretic action via a CNS mechanism. Fever is thought to occur because endogenous pyrogens cause a shift in the temperatureregulating system in the preoptic hypothalamus.

NSAIDs are postulated to reduce the effect of endogenous pyrogens on the hypothalamus. In therapeutic doses, NSAIDs do not affect either normal

body temperature or an increase in temperature

associated with exercise, drugs, or hypothalamic

lesions to which pyrogen does not contribute. Salicylates, acetaminophen, and ibuprofen are the only

drugs approved in the United States as antipyretics,

although indomethacin and naproxen have been

recommended as drugs to lower fever of neoplastic

disease that is uncontrolled by other antipyretics.50
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301

Antiinflammatory Effect

Since prostaglandins induce symptoms of inflammation and enhance the effects of bradykinin

and histamine, a reduction of prostaglandins at

sites of inflammation is thought to decrease the

inflammatory response. In arthritic diseases,

NSAIDs reduce inflammation and swelling, thereby

providing relief.50

Side Effects

Gastrointestinal System

All NSAIDs can cause gastrointestinal pathology, including gastritis, nausea, vomiting, diarrhea,

constipation, and occult blood in the stool.48,49 Gastrointestinal problems are more common with

aspirin, indomethacin, and mefenamic acid49 although nonacetylated salicylates may be less irritating.50 Alcohol ingestion increases the likelihood

that gastrointestinal side effects will occur.49 The

United States Pharmacopeia recommends that all

NSAIDs be taken with a full glass of water.49

NSAID-associated gastropathy has been proposed

as the most frequent, serious, adverse drug effect

in the United States; the risk of gastrointestinal

problems is greater in elderly and debilitated patients.50

Aspirin should be avoided by patients with a

history of ulcers and should not be used with agents

that promote ulcer formation (eg, alcohol). The

mechanisms of gastrointestinal bleeding and

NSAID-induced ulceration are due in part to irritation from direct contact with mucosal cells and

cyclooxygenase inhibition after absorption, which

weakens the gastric-acid barrier. Chronic inhibition of prostaglandin synthesis appears to decrease

mucosal cytoprotection. It is likely that aspirininduced bleeding is aggravated by its effect on

platelet aggregation.50

Renal System

Renal prostaglandins are important to ensure

adequate renal perfusion and function in certain

disease states, including congestive heart failure,

cirrhosis with ascites, nephrotic syndrome, and

dehydration. In these patient groups, NSAIDs may

precipitate acute renal failure. Long-term use of

high-dose NSAIDs may cause renal medullary

ischemia and papillary necrosis. This was more

common when phenacetin was used, especially in

combination with aspirin, caffeine, and acetaminophen. Phenacetin has been replaced with acetaminophen, which may also be a risk factor for

papillary necrosis. Renal prostaglandins inhibit

tubular reabsorption of Na+ and water, and inhibit

renin secretion. In patients with poor renal perfusion states, NSAIDs may cause fluid retention, impaired responsiveness to diuretic therapy, and

hyperkalemia.50

Respiratory System

Inhibition of bronchodilator prostaglandins by

NSAIDs may leave the leukotriene pathway uncontested and lead to bronchospasm.49 This may be a

consideration in susceptible patients such as asthmatics. Full therapeutic doses of salicylates increase oxygen consumption and carbon dioxide

production in skeletal muscle. Higher doses result

in medullary stimulation, causing hyperventilation

with a respiratory alkalosis. This is compensated

for by excretion of bicarbonate by the kidneys, which

leads to a compensated respiratory alkalosis. Toxic

doses of salicylate depress the medulla, leading to

an uncompensated respiratory acidosis in a patient

with high renal bicarbonate excretion, which, in

turn, leads to a coexisting metabolic acidosis.48

Hematological Effects

NSAIDs inhibit both thromboxane A2 synthesis

within platelets and prostacyclin synthesis within

endothelial cells. Thromboxane A2, a potent vasoconstrictor, stimulates platelet aggregation, which

promotes clotting. Prostacyclin, a potent vasodilator, inhibits platelet aggregation, which promotes

bleeding. NSAIDs inhibit the synthesis of both

thromboxane A2 and prostaglandin I2. The net

balance determines the tendency towards bleeding

or clotting.51

Aspirin irreversibly inhibits platelet cyclooxygenase which prevents the formation of thromboxane A2,thereby inhibiting platelet aggregation. The

bleeding time is prolonged for the lifetime of the

platelet. All other NSAIDs reversibly inhibit platelet cyclooxygenase, so that five half-lives are required to clear all the drug from the body and

restore normal platelet function.51

Reye’s Syndrome

Reye’s syndrome, a childhood illness that develops after recovery from influenza or chickenpox, is

characterized by vomiting, liver abnormalities, and

encephalopathy. Nearly all victims of Reye’s syn-
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302

drome had received salicylates for management of

the viral illness. If an analgesic antipyretic is required for use in children with acute viral illness,

acetaminophen should be used, as there is no evidence of an association between acetaminophen

and Reye’s syndrome.50

CLINICAL PHARMACOLOGY OF LOCAL ANESTHETICS

Since prehistoric times, the natives of Peru have

chewed the leaves of the indigenous plant

Erythroxylon coca, the source of cocaine, to obtain a

feeling of well-being and to reduce fatigue.9,52 Chewing of the coca leaves caused a reversible perioral

numbness, and subsequent investigation of the coca

leaf allowed the identification of cocaine, the active

ingredient. Cocaine was used as a topical ocular

anesthesia and for nerve blocks during the latter

18th century.49 Addictive properties and toxicity

limited the use of cocaine for local anesthesia, but

this finding stimulated research for more ideal local

anesthetic agents. Einhorn introduced the esters

procaine in 1905 and tetracaine in 1932, and Lofgren

introduced lidocaine, an amide, in 1932.9

Local anesthetics are important adjuncts to the

management of postoperative pain; they significantly reduce the amount of narcotics necessary to

maintain a pain-free state in the postoperative patient.7 A simple system governs the naming of local

anesthetic drugs: those spelled with one i in the

name are esters (eg, procaine, 2-chloroprocaine,

tetracaine); those with two are amides (eg, lidocaine,

mepivacaine, bupivacaine). Among the amides,

stereoisomers of etidocaine, mepivacaine, bupivacaine, prilocaine, and ropivacaine have been recognized. Although the S forms of these molecules are

generally less toxic and have a longer duration of

action,53 the chiral forms of local anesthetics are not

discussed in this chapter.

Very dilute solutions of a local anesthetic combined with an opiate produce anesthesia comparable to that produced by more-concentrated solutions of plain local anesthetics. Use of dilute solution

of local anesthetic causes less motor blockade, which

facilitates postoperative ambulation. The interaction of opiates and local anesthetics is postulated to

be due to a synergistic action of the drugs (administered epidurally) acting in two or more different

sites to decrease sensory input. The local anesthetics act at the dorsal root ganglion while the opiates

act on the dorsal horn of the spinal cord.53

Chemical and Physical Properties

The potency, onset of action, and duration of

local anesthetic action are directly related to the

physical properties of lipid solubility, pKa (ie, ionization), and protein binding (Figure 13-3).53 Local

anesthetics consist of a lipophilic, unsaturated, benzene-ring aromatic group; and a hydrophilic, tertiary amine separated by a hydrocarbon connecting

chain (Figure 13-4). Clinically useful local anesthetic agents fall into two chemically distinct groups,

based on the linkage between the aromatic portion

and the intermediate chain.52 This linkage can be

via an ester (–CO–) or an amide (–HNC–) bond. The

ester and amide compounds differ in their chemical

stability, metabolic cycles, and allergic potentials.

In general, the greater the length of the connecting group and the more complicated the aromatic

and amine structures, the greater the potency and

the toxicity of the local anesthetic.48 The addition of

more complicated side chains to local anesthetics

causes an increase in their tissue-protein binding

ability and also makes the drug more fat soluble,

thereby increasing the duration of action.49

Lipid Solubility

The aromatic group (ie, the benzene ring) that is

present at one end of the molecule is the major

determinant of the lipid solubility of local anesthetic drugs. The more-lipid-soluble drugs are the

more-potent local anesthetics, probably because the

lipid-soluble uncharged base form can pass through

the lipid-containing nerve membrane to reach its

site of action.53

Fig. 13-3. The general structure of a local anesthetic

molecule.

N H+ NH+

Intermediate chain

(Ester or amide linkage)

Benzene ring

(Lipophilic)

Quaternary amine

(Hydrophilic)
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303

Cocaine

2-Chloroprocaine

Tetracaine

Lidocaine

Prilocaine

Etidocaine

Mepivacaine

Bupivacaine

Ropivacaine

Fig. 13-4. Chemical structures of commonly used local anesthetics.

Procaine H2N C

O

OC N

H

H

C2H5

C2H5

C

H

H

N

H

C C

H

H

N

O C2H5

C2H5

CH3

N

H

C C

H

CH3

N

O H

C3H7

CH3

N

H

C C

O

CH3

CH3

H

C2H5

N

C2H5

C3H7

N

H

C

O

CH3

CH3

N

CH3

N

H

C

O

CH3

CH3

N

C4H9

Amino Amides

Amino Esters

C

H

O C

C C

C

O O

H3C

C

C

H

C

C

N CH3

C

O

OC N

H

H

CH3

CH3

C

H

H

H9C4 N

H

C

O

OC N

H

H

C2H5

C2H5

C

H

H

H N

H

Cl

N

H

C

O

CH3

CH3

N

C3H7
Anesthesia and Perioperative Care of the Combat Casualty

304

Ionization

Local anesthetic molecules contain an amino

group, which determines the hydrophilic activity

and ionization of the molecule. The amino group is

capable of accepting a hydrogen ion, which converts the nonionized base form of the drug into the

cationic (ie, charged) form. The proportion of each

form (nonionized base and cation) present is determined by the pKa of the drug and the pH of the

solution (pKa is defined as the pH at which 50% of

the drug is ionized and 50% is present as the free

base). The nonionized (free base) form penetrates

the nerve membrane and the ionized (cationic) form

produces blockade of the sodium channel. With

many local anesthetics, the speed of onset can be

related to the degree of difference between the pKa

of the drug and the pH of the normal human body.53

As a general rule, the lower the pKa of the local

anesthetic, the shorter the onset time for induction

of anesthesia. The closer the pH of the injected

solution of local anesthetic is to body pH, the shorter

the onset time. Commercial preparations of local

anesthetics are made more acidic to enhance stability, which favors the formation of the cationic form

(Figure 13-5).53

Protein Binding

Anesthetics are not pharmacologically active

while in their protein-bound form. In the plasma,

local anesthetics bind to albumin (a low-affinity,

high-capacity binding) and to α1-acid glycoprotein

(a high-affinity, low-capacity binding). The binding of local anesthetics to proteins is concentrationdependent and decreases in a curvilinear manner as

the local anesthetic concentration in plasma increases. So the potential for toxicity increases

disproportionally with increases in plasma concentration.53

Protein binding of local anesthetics is influenced

by the pH of the plasma. The percentage of bound

drug decreases as the pH decreases. Therefore,

acidosis potentiates the toxicity of local anesthetics

by increasing the fraction of the active form of

the drug—both in the circulation and at the active

site.53 Protein binding of local anesthetics, which

is decreased in newborns and pregnant women,

causes an increase in the free fraction of local anesthetic.53 α1-Acid glycoprotein is decreased in elderly individuals, pregnant women, and newborns.

Premature infants have approximately one half the

α1-acid glycoprotein that is present in newborns.53

The fraction of drug that is bound to protein in

Fig. 13-5. Equilibrium between the base and the cationic

forms of a local anesthetic.

plasma correlates with the duration of activity of

the local anesthetic. Bupivacaine and etidocaine

are 95% protein bound. These drugs last longer

than lidocaine, which is 65% protein bound. Recently, researchers have speculated that there

may be a similarity between the binding of the

local anesthetic molecule to plasma protein and

the binding to the receptor protein in the sodium

channel.54

Mode of Action

The local anesthetics in clinical use today are

sodium channel–blocking agents. They exert their

effect by inhibiting the influx of Na+ across the

neuronal cell membrane. This produces a conduction blockade of nerve impulses by preventing increases in permeability of nerve membranes to Na+

If the permeability to Na+ fails to increase, the rate

of depolarization will slow such that the threshold

potential is not reached and an action potential is

not propagated. The ionic gradients and the resting-membrane potential of the nerve are unchanged,

but the increase in Na+ permeability that is associated with the nerve impulse is inhibited. Local

anesthetics do not alter the resting transmembrane

potential or the threshold potential.52

The theories of the mechanism of action include

(a) the displacement of Ca++ from a membrane site

N

CH3

CH3

CH3

N

CH3

C

C

O

O

C

C

H

H

N

H

H

N+

C2H5

C2H5

H

C2H5

C2H5

Base Form

Cationic Form

H +
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305

that controls Na+ permeability, (b) the MeyerOverton rule of anesthesia, (c) a change in surface

charge, and (d) the specific-receptor theory.

Displacement of Calcium

A low calcium concentration outside the neuron

enhances local anesthetic activity, while an increasing external calcium concentration antagonizes local anesthetic activity. However, the direct actions

of calcium and local anesthetic appear to be independent of each other.9

Meyer-Overton Rule

The Meyer-Overton rule of anesthesia postulates

that diffusion of the relatively lipophilic anesthetic

molecules into the lipid component of the neuronal

membrane expands the membrane to a critical volume and interferes with sodium conductance. Local anesthetics have been shown to increase the

volume of lipid membranes and increase their degree of disorder. High-pressure antagonism of the

anesthetic activity of certain uncharged local-anesthetic molecules such as benzyl alcohol and

benzocaine has been seen. Pressure reversal has not

been shown to occur in the case of charged local

anesthetics. These findings indicate charged and

uncharged local anesthetics may have separate sites

of action.9,55

Change in Surface Charge

A third proposal for the mechanism of action of

local anesthetics involves the induction of alterations in the membrane surface charge. The cationic molecule neutralizes, to a variable degree, the

fixed negative charges on the inside membrane

surface, altering the transmembrane potential. If

the molecule of local anesthetic is absorbed into the

extracellular side of the axonal membrane, the extra

positive charges add to the already relatively positive extracellular charge and hyperpolarize the

membrane. This hyperpolarization makes it harder

for a nerve impulse to raise the transmembrane

potential to the depolarization threshold. If the

local anesthetic is absorbed into the intracellular

side of the axonal membrane, the increase in positive charge could prevent sufficient repolarization

of the membrane interior to allow reactivation of

the sodium channels that were inactivated by a

previous action potential. The surface-charge theory

could account for the antagonism between divalent

cations such as calcium and local anesthetics.9

Specific-Receptor Theory

The specific-receptor theory postulates that local

anesthetics interact directly with specific receptors

in the neuronal membrane. This interaction affects

specific ion channels of the neuronal membrane in

such a fashion that the ionic flux needed for initiation and propagation of the action potential is inhibited. The structure of the sodium channel is that

of a lipoglycoprotein that spans the neuronal membrane and contains an aqueous pore that is able to

discriminate between sodium and other ions, being

selectively more permeable to sodium.9 Intrinsic

electrical properties of the macromolecules that

compose the channel allow it to change configuration in response to changes in the membrane potential, thus determining the conductance of sodium

ions across the axolemma.

The sodium channel can exist in three states:

closed (ie, resting), open, and inactivated.10 When a

nerve impulse occurs and the sodium channel goes

through the open to the inactivated state, it carries

another impulse until it repolarizes and returns to

the resting state. Immediately following an action

potential, many of the sodium channels are in the

inactivated state and cannot be reopened by a subsequent voltage change. So once an excitable membrane has been depolarized by an action potential,

it cannot conduct a second impulse until it has first

repolarized and allowed inactivated sodium channels to return to their resting state. If an adequate

number of sodium channels are not present in the

resting state, sodium current sufficient for a second

action potential cannot be generated.9,10

Frequency-Dependent Blockade

The property of frequency-dependent blockade

(ie, use-dependent blockade), in which neuronal

blockade by charged local anesthetic molecules increases with repetitive, brief, membrane depolarizations, is one phenomenon that suggests direct

interaction between sodium channel receptors and

the charged local anesthetic molecules. It is postulated that frequency-dependent blockade develops

because charged, hydrophobic, anesthetic molecules

inhibit Na+ conductance through the sodium channel by gaining access to a channel receptor located

within the channel itself, while the pore of the

sodium channel is open. For this reason, selective

conduction blockade of nerve fibers by local anesthetics may be related to the nerve’s characteristic

frequencies of activity (ie, selective conduction

blockade occurs more readily in a rapidly firing
Anesthesia and Perioperative Care of the Combat Casualty

306

nerve).9,10 Reversal of the inhibitory effect of the

local anesthetic also requires an open channel pore

to facilitate the dissociation of the molecule of local

anesthetic. Consequently, a closed channel containing a local anesthetic molecule would be slow to

return to its uninhibited state.9,10

In contrast to charged anesthetics, neutral anesthetics exhibit much less frequency-dependent

blockade; this may be because they are not restricted to the aqueous phase and can gain access

through the lipid milieu of the membrane interior.

Local anesthetics may also shift the sodium channel

population to a nonconducting state by binding

channels that have already been inactivated, preventing their return to the resting depolarizationsusceptible configuration. A weak tonic (ie, resting) block may be induced by binding with channels

in the resting (closed) state to prevent their voltageinduced activation.

The discovery that the blocking potency of local

anesthetic molecules is much greater when the interaction is with receptors of open and inactivated

channels, as compared to those of closed channels,

has led to the modulated-receptor hypothesis of

local anesthetic receptor binding. According to the

modulated-receptor hypothesis, local anesthetics

have a higher affinity for open and inactivated

sodium channels than for closed channels. During

stimulation, channels that are open and inactivated

bind local anesthetics more tightly. This binding

stabilizes the channels in a nonconducting state,

and increasingly so with each stimulating pulse.9

The variable state of the local anesthetic receptor

determines the strength of its interaction with the

local anesthetic molecule. An excitable membrane

with a higher depolarization frequency will be more

sensitive to the blocking effects of local anesthetics.

This theory offers an explanation for frequencydependent blockade.

Receptor Sites in the Sodium Channel

It is uncertain as to exactly where in the sodium

channel the local-anesthetic receptors are located.

Three sites of binding are postulated9,10:

1. near the interior opening; this area has an

affinity for charged local anesthetic molecules;

2. at the interface between the channel and

membrane lipid; this area has an affinity for

uncharged molecules; and

3. at the outer aspect of the sodium channel;

this area is the site of actions of toxins such

as tetrodotoxin.

Fig. 13-6. A molecule of local anesthetic moves through a

lipid bilayer and enters the sodium channel. On the

drawing, B represents the base form of a local anesthetic

and BH+ represents the cationic form. Reprinted with

permission from DiFazio CA, Woods AM. Drugs commonly used for nerve blocking. Pharmacology of local

anesthetics. In: Raj PP, ed. Practical Management of Pain.

St. Louis, Mo: Mosby–Year Book; 1992: 690.

Figure 13-6 shows the nonionized base form

of the local anesthetic molecule diffusing through

the neural lipid bilayer. Inside the nerve, the equilibrium is established between the free base and

cationic forms of the local anesthetic. The ionized

cationic form enters the sodium channel from the

intracellular side of the nerve membrane, binding to an anionic site, which blocks the sodium

channel.53

Actions of Local Anesthetics on Nerve Fibers

Actions of local anesthetics on nerve fibers generally depend on the diameter of the fiber and the

length of the fiber exposed to the agent. These two

related characteristics are discussed below.

Minimum Length of Exposed Nerve

A minimum length of myelinated nerve fiber

must be exposed to an adequate concentration of

local anesthetic for nerve block to occur. Conduction blockade is predictably present if at least three

successive nodes of Ranvier are exposed to adequate concentration of local anesthetic.49 Both

types of pain-conducting fibers (ie, myelinated type

A-delta and nonmyelinated type C fibers) are

blocked by similar concentrations of local anesthetics despite their differences in diameter. Pregangli-
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307

onic type B fibers are more readily blocked by local

anesthetics than any other fiber, even though these

fibers are larger in diameter than type C fibers (type

B fibers are myelinated; type C are not).

Differential Blockade

It has long been a clinical observation that all

neuronal functions are not affected equally by local

anesthetics. Blockade of the components of a peripheral nerve may proceed at different rates, with

loss of sympathetic function first, followed by

pinprick sensation, touch and temperature, and,

lastly, motor function. Or there may be relative

sparing of one neuronal function over another (eg,

low-dose bupivacaine labor epidural, with its relatively intact motor tone). There are several potential explanations for differential blockade:

1. The fiber’s diameter is inversely proportional to the fiber’s susceptibility to local

anesthetic blockade.

2. Internodal distance is proportional to the

axon diameter, so the equivalent spread of

local anesthetic may produce conduction

blockade of a thin axon but not of the adjacent thick axon (Figure 13-7).

3. C fibers may be blocked faster, owing to the

relatively unimpeded local anesthetic access to the axon.

4. The slower local anesthetic block of A fibers

depends on the pKa and the lipid partition

coefficient of the local anesthetic molecule.

The lower the pKa (the greater the percentage of

lipophilic uncharged molecules at physiological pH)

and the greater the lipid partition coefficient of the

local anesthetic molecule, the more rapid the onset

of block in A fibers. In high concentrations, even a

relatively hydrophilic local anesthetic can produce

a rapid block of A fibers because of the greater

diffusion gradient, causing a rapid transit across

the myelin sheath. Thus, the use of a less–lipidsoluble local anesthetic would most likely result in

differential block of A-delta and C fibers at the

onset of the nerve block. The differential block seen

with bupivacaine is believed to be due to the relatively high pKa of this agent, such that fewer uncharged molecules are available to penetrate the

diffusion barriers surrounding large A fibers. Differential blockade may be the manifestation of a

frequency-dependent process with more–rapid-firing axons being sensory and slower-firing axons

being somatic motor efferents.

Fig. 13-7. Differential blockade of myelinated nerve fibers of different diameters. Internodal distance is proportional to axon diameter. Conduction blockade occurs

when at least three adjacent nodes of Ranvier are blocked.

This drawing shows the blockade of a thin myelinated

axon occurring before a block will be established in a

thicker myelinated fiber. Adapted with permission from

Franz DN, Perry RS. Mechanisms for differential block

among single myelinated and non-myelinated axons by

procaine. J Physiol. 1974;236:207.

Anesthetic

Thin Axon

Thick Axon

Differential block may also be a reflection of the

geographical arrangement of the nerve fibers within

the peripheral nerve, with the outermost fibers being

blocked preferentially if the local anesthetic solution

is dilute. The local anesthetic diffuses from the outer

surface (ie, the mantle) toward the center (the core)

along a concentration gradient. The mantle is blocked

first. These are the more proximal structures. The core

is the more distal structure. Skeletal muscle paralysis

may precede the onset of sensory blockade if motor

nerve fibers are distributed peripheral to sensory fibers in the mixed peripheral nerve (Figure 13-8).

Pharmacokinetics

Pharmacokinetics denotes the movement of a drug

through the body: movement into the bloodstream,

movement from blood into tissues, and movement

out of the body by metabolism and excretion. When

regional anesthesia is sought, the local anesthetic is

injected in close proximity to the site of desired

effect so that local, physical factors become more

important than systemic pharmacokinetic factors

for predicting the desired pharmacodynamic effects. The concentration of local anesthetic that

develops in neural tissue is affected by the proximity of the injected anesthetic to the nerve, the flow of

anesthetic around the nerve tissue, diffusion across
Anesthesia and Perioperative Care of the Combat Casualty

308

Fig. 13-8. Somatotropic arrangement of fibers in a neuron. Local anesthetics diffuse along a concentration gradient to block the mantle fibers before the core bundle.

This is the explanation for anesthesia occurring in more

proximal areas of the extremity first. Reprinted with

permission from Stoelting R, Miller R. Basics of Anesthesia. 2nd ed. Philadelphia, Pa; JB Lippincott; 1989: 84.

the tissue barriers and into the nerve, binding to

nonneural tissues, and absorption into the vascular

and lymph system.

Both local carbon dioxide partial pressure and

temperature are determinants of the pharmacokinetics of local anesthetics. Making local anesthetics from the carbonate salt rather than the hydrochloride salt and adding carbon dioxide to the

solution yields a better-quality neural blockade.

This approach both shortens the time of onset and

improves the neural blockade. This effect may be due

to (1) elevated carbon dioxide, which causes a direct

neural blockade, and (2) increased carbon dioxide in

the axoplasm, which causes an increase in ion trapping of the local anesthetic in the axoplasm by

favoring the shift of nonionized free base form to

the impermeable ionized form of local anesthetic.53

Warming the local anesthetic solution increases the

pKa of the local anesthetic so that at a constant pH,

warming results in an increase in the fraction of free

base available. Warming the local anesthetic solution causes a consistently faster onset of action.53

Bulk Flow

A large volume of local anesthetic solution will

spread by bulk flow to a greater extent and produce

a greater spread of nerve block. Concentration (or

total mass of drug) also affects the spread, probably

by influencing diffusion gradients. Separating the

effects of volume, concentration, and mass is difficult. A minimum volume is probably necessary to

provide adequate spread around the nerve. A minimum concentration is necessary to provide an adequate diffusion gradient to penetrate the nerve.

Once these minimum values have been attained, the

total mass of drug becomes important.

Diffusion and Binding

The rapidity and extent of diffusion depends to

largest extent on the pKa of the local anesthetic, the

concentration injected, and the lipid solubility. The

ionized form of the drug diffuses poorly, whereas,

the nonionized free base is freely diffusible. Alkalinization of the injected solution will increase the

proportion of nonionized drug and should facilitate diffusion. Acidosis from local infection will

retard diffusion of local anesthetic because of increased ionization. Local anesthetics with high

lipid solubility can penetrate neural membranes

more readily but they also have more nonspecific

binding, which can impede diffusion to the specific

site of action.

Systemic Absorption

The most important factors affecting peak blood

level (Cmax) are (a) the total dose of local anesthetic,

which is almost a linear relationship, and (b) the site

of injection (see Chapter 12, Regional Anesthesia,

Figure 12-2), in the following relationship:

intercostal > caudal > epidural >

brachial plexus > sciatic or femoral

When a 1 mg/kg dose of local anesthetic is given

as an epidural or caudal injection, a peak blood

level of approximately 1 μg/mL results. When a 1

mg/kg dose of local anesthetic is given in a lessvascular area (eg, the brachial plexus) or as a subcutaneous infiltration, a peak blood level of approximately 0.5 μg/mL is seen. During an intercostal

block, a peak blood level of 1.5 μg/mL occurs. Peak

blood levels may be seen 10 to 30 minutes after

injection.53
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309

The peak blood levels that are seen after injection

are affected by the rate of local anesthetic biotransformation and elimination. For amides, this effect is

small. For example, 70% of the lidocaine presented

to the liver undergoes hepatic extraction. This is

limited by hepatic blood flow and the low concentration of local anesthetic in the plasma after a nerve

block is performed.53 Biotransformation is the primary determinant of the very low plasma levels

that occur after a nerve block by an ester local anesthetic. Due to their metabolism by plasma cholinesterase, esters such as 2-chloroprocaine have a

plasma half-life of approximately 45 seconds.53

Distribution, Metabolism, and Elimination

Once a local anesthetic is absorbed into the blood,

it is distributed first to the lung, where local anesthetics have a high solubility. On reaching the

systemic circulation, distribution is determined by

tissue blood flow. The local anesthetics go first to

vessel-rich groups and then are redistributed into

tissues with lower relative perfusions.

The amide local anesthetics are extremely stable

agents; esters are relatively unstable in solution.

Amino esters are hydrolyzed in plasma by plasma

cholinesterase. Patients with atypical plasma cholinesterase may be at increased risk for developing

excessive plasma concentrations of ester local anesthetics. Amide compounds undergo hepatic microsomal metabolism. Hepatic disease or reductions in hepatic blood blow—such as those that

occur with congestive heart failure or during general anesthesia—can reduce the rate of local clearance of amide local anesthetics.

If a patient develops seizures and becomes

acidotic, the local anesthetic that has accumulated

in the brain will be more ionized and unable to cross

the lipid blood–brain barrier for redistribution.

Acidosis also modifies the pharmacokinetics of local anesthetics in the fetus. When a fetus is depressed and more acidotic, the uncharged, absorbed

local anesthetic that crosses the placenta will become ionized and be trapped in the fetus.49

Expedited Onset and Prolongation of Action

Expedited Onset. Onset of local anesthesia can

be expedited by increasing the nonionized lipidsoluble form of local anesthetic. As discussed previously, this is the form of local anesthetic that can

penetrate the nerve membrane. The fraction of the

free base (nonionized) form and the cationic (ionized) form is determined by the pKa of the drug and

the pH of the drug solution, and the pH of the tissue

in which the drug is injected.53 Adjustment of the

pH by alkalinizing the injectate shifts the equilibrium towards the nonionized free-base form of the

local anesthetic, so that more molecules are available to penetrate the nerve membrane. Increases in

the amount of free base in solution are limited by

the solubility of the free base in solution. After a

saturated solution of free base is achieved, further

alkalinization will result in precipitation of the

drug.53 Local anesthetics often fail to work in areas

of local acidosis (eg, an abscess). In these areas, the

equilibrium between charged and uncharged forms

of the anesthetic is shifted in favor of the charged

form as a result of the abundance of hydrogen ions.

This decreases the amount of uncharged local anesthetic available to diffuse through the neural membrane to initiate anesthesia.49

Prolongation of Action with Epinephrine. The

addition of epinephrine (1:200,000, 5 μg/mL) or

phenylephrine (2 mg) to local anesthetic solutions

that are to be injected produces local tissue vasoconstriction, which limits systemic absorption, and

prolongs the duration of action by keeping the local

anesthetic in contact with nerve fibers.52

In the presence of volatile anesthetics, systemic

absorption of epinephrine may contribute to cardiac dysrhythmias, or accentuate hypertension in selected patients (eg, those with preeclampsia or

thyrotoxicosis). Addition of epinephrine is not recommended52 in patients with

• unstable angina pectoris,

• cardiac dysrhythmias,

• uncontrolled hypertension,

• uteroplacental insufficiency,

• peripheral nerve block in areas lacking collateral blood flow (eg, the digits, penis, nose), or

• those receiving intravenous regional anesthesia.

Commercially prepared local anesthetic solutions

with epinephrine are pH-adjusted to a more acidic

environment, which creates stability for the epinephrine (see Table 12-2 for appropriate doses of

commonly used local anesthetics).53 Alkalinization

of these solutions improves onset time for anesthesia. If epinephrine is added to plain local anesthetic solution, the onset time is improved because

the pH of the plain solution is higher (pH 6.5)

than the pH of the commercially prepared, pH-adjusted, epinephrine-containing local anesthetic solution (pH 4.5).53
Anesthesia and Perioperative Care of the Combat Casualty

310

CVS depression

Respiratory arrest

Coma

Convulsions

Unconsciousness

Muscular twitching

Visual disturbance

Lightheadedness

Numbness of tongue

30

25

20

15

10

5

0

Lidocaine Plasma Concentration (μg/mL)

numbness and buzzing or ringing in the ears may be

seen. With levels of 10 to 12 μg/kg, seizures are

seen, which are due to selective blockade of inhibitory pathways in the brain, leaving facilitatory neurons unopposed. Before the onset of seizures, patients have slow speech, jerky movements, tremors,

and hallucinations. Cardiac toxicity is seen with

levels of 20 to 25 μg/kg.53

Bupivacaine blood levels of 4 μg/mL causes seizures, while with higher doses (6 μg/mL), cardiac

toxicity is seen.53

Central Nervous System Toxicity

CNS toxicity manifests as seizure activity. If

seizure activity is not rapidly stopped, acidosis

progresses due to anoxia, which decreases protein

binding of the local anesthetic, creating more free

(unbound) active drug. This is treated primarily by

preventing the detrimental effects of hypoxia and is

accomplished by the following protocol53:

• Ventilate with 100% oxygen.

• Suppress the seizures by raising the seizure

threshold of the CNS with intravenous

thiopental (50–100 mg if myocardial function is not depressed), midazolam (1–2 mg),

or diazepam (5–10 mg).

• Patients with severe toxicity should be

intubated. Succinylcholine may be used to

facilitate intubation.

• Termination of the tonic clonic muscle activity with muscle paralysis will prevent

further acidosis due to increased muscle

activity.

Cardiotoxicity

All local anesthetics cause a dose-dependent depression of contractility of cardiac muscle. This

cardiodepressant effect on contractility parallels

the anesthetic potency of local anesthetics in blocking peripheral nerves (bupivacaine has 4-fold more

cardiac toxicity than lidocaine).53

Progressive prolongation of ventricular conduction predisposes to reentrant phenomena. Widened QRS is followed by a sudden onset of ventricular fibrillation. All local anesthetics produce a

dose-dependent depression of conduction velocity

in cardiac tissue, including intraatrial, AV nodal,

His-Purkinje, and intraventricular pathways.53

Bupivacaine is 4-fold more cardiotoxic than

lidocaine, perhaps because with depolarization of

the cardiac sodium and calcium channels, lidocaine

Fig. 13-9. Toxic effects of local anesthetics produced by

increasing lidocaine plasma levels. CVS: cardiovascular

system. Reprinted with permission from Carpenter RL,

Mackey DC. Local anesthetics. In: Barash PG, Cullen BF,

Stoelting RK, eds. Clinical Anesthesia. Philadelphia, Pa: JB

Lippincott; 1989: 389.

Toxic Effects:

Toxicity

Central nervous system (CNS) toxicity in the

form of seizures occurs at a lower blood level than

cardiac toxicity (Figure 13-9). Excessively high

blood levels of local anesthetic can result from various mishaps, including the following:

• accidental intravascular injection of a large

amount of local anesthetic,

• premature release of a tourniquet during a

Bier block,

• administration of an improper dose for the

site of administration (absorption into the

bloodstream depends on the site of administration), and

• administration of a local anesthetic to a patient with an allergy to the drug.

Toxicity should be prevented by the means described in Exhibit 13-1. Table 13-6 compares safe

doses (in mg/kg) of local anesthetics between various agents and areas of injection. Peripheral blocks

are slowly absorbed, which allows administration

of a higher dose, compared with an intercostal block,

which is rapidly absorbed.

Blood levels of lidocaine of 1 to 5 μg/mL are

therapeutic for treating cardiac arrhythmias and as

a supplement to general anesthesia. With levels of

3 to 5 μg/mL, systemic symptoms such as circumoral
Perioperative Pain Management

311

EXHIBIT 13-1

PREVENTION OF LOCAL ANESTHETIC–INDUCED TOXICITY

1. Be familiar with the local anesthetic agent being used.

2. Select a dose that should be associated with clinically safe blood levels at the site of injection.

3. Administer the drug in a manner that identifies an unintended intravascular injection:

• Fractionate the dose by injecting 3- to 5-mL increments of local anesthetic so that an intravenous or

intrathecal injection can be identified before a large amount of drug has been administered.

• Aspirate frequently during injection to identify intravenous or intrathecal injections.

• Maintain verbal contact with the patient to identify early subjective sensations such as circumoral tingling

and ringing in the ears.

• Inject a small test dose of epinephrine in a 1:200,000 concentration to elicit an increase in heart rate with

inadvertent intravascular injection.

• Injecting a small amount of air before injecting local anesthetic, combined with precordial Doppler

monitoring, may detect intravenous injections.

• Have resuscitation equipment available when local or regional anesthesia is performed.

4. Have a knowledge of the patient’s medical history (hepatic/renal disease or allergy to p-aminobenzoic acid).

Data source: Warfield D. Manual of Pain Management. Philadelphia, Pa: JB Lippincott; 1991.

rapidly enters and leaves the open channels (ie, the

fast-in, fast-out effect). Bupivacaine, on the other

hand, rapidly enters the channels but binds the

proteins in the channel causing a fast-in, slow-out

effect, which strongly blocks inactivated open cardiac channels. This prevents the channels from

recovering during diastole, leading to increased

susceptibility to reentrant dysrhythmias.53

TABLE 13-6

COMPARABLE SAFE DOSES OF LOCAL ANESTHETICS (MG/KG)*

Areas Injected

Central Blocks† Intercostal Blocks§

Drugs Peripheral Blocks‡ Plain With Epi 1:200,000 with Epi 1:200,000

2-Chloroprocaine — 20 25 —

Procaine — 14 18 —

Lidocaine 20 7 9 6

Mepivacaine 20 7 9 6

Bupivacaine 5 2 2 2

Tetracaine — 2 2 —

*Estimated to produce peak plasma levels that are less than half the plasma levels at which seizures could occur

†Areas of moderate vascularity (ie, caudal epidural blocks)

‡Areas of low vascularity (ie, axillary blocks using local anesthetic solutions containing 1:200,000 epi)

§Areas of high vascularity (ie, intercostal blocks using local anesthetic solutions containing 1:200,000 epi)

Epi: epinephrine

Reprinted with permission from DiFazio CA, Woods AM. Drugs commonly used for nerve blocking. Pharmacology of local

anesthetics. In: Raj PP, ed. Practical Management of Pain. St. Louis, Mo: Mosby–Year Book; 1992: 695.
Anesthesia and Perioperative Care of the Combat Casualty

312

Acidosis increases cardiotoxicity of local anesthetics by decreasing protein binding, which increases the free (active) fraction of the drug. Acidosis also increases the ionized form of the local

anesthetic, which is the active form in blocking

cardiac channels.53

Therapy for local anesthetic–induced cardiotoxicity employs the following protocol:

• Institute adequate ventilation.

• Terminate the seizures.

• Support blood pressure with fluids, vasopressors, or cardiopulmonary resuscitation.

• Institute antiarrhythmia therapy with

bretylium or magnesium sulfate.

• In some cases, remove the offending agent

by means of iontophoresis.

Cardiotoxicity of the long-acting local anesthetics may be increased in the patient who is pregnant.

Lower doses of bupivacaine are required to produce cardiotoxicity in pregnant ewes compared to

nonpregnant controls.53 This may be due, in part, to

the fact that protein binding is decreased during

pregnancy, causing an increased fraction of free

drug.

Allergy to Local Anesthetics

p-Aminobenzoic acid is one of the metabolites of

esters and related compounds that can induce allergic reactions in some patients. Amino amides, on

the other hand, are not metabolized to p-aminobenzoic acid, and reports of allergic reactions to these

agents are extremely rare.

SELECTION OF LOCAL ANESTHETICS

Local anesthetics are selected based on (a) the

duration of anesthesia needed, (b) the need for

motor blockade, and (c) the speed of their onset of

action.53

Esters

Procaine

Procaine, the first synthetic local anesthetic, is

characterized by slow onset and short duration of

action. It penetrates tissue barriers poorly. Procaine

is metabolized to p-aminobenzoic acid, which has

allergenic potential.

2-Chloroprocaine

The 2-chloro- derivative of procaine, 2-chloroprocaine has a rapid onset of action and a short

(30–60 min) duration of activity. Its half-life is

45 seconds in the plasma. 2-chloroprocaine has

a low potential for systemic toxicity owing to

its rapid breakdown. Sensory deficits have occurred with inadvertent intrathecal administration due to bisulfite, the preservative that was

added. Bisulfite is an acidic solution that releases sulfur dioxide, forming neurotoxic sulfurous

acid. Bisulfite has been removed from the preparation and ethyl-enediaminetetraacetic acid

(EDTA) substituted. EDTA may cause spasm of

back muscles after epidural administration owing

to EDTA’s binding of calcium in the paraspinal

muscles.53

Tetracaine

Tetracaine, the butyl aminobenzoic acid derivative of procaine, is potent and long acting. This

drug is usually used for spinal analgesia in a dose of

6 to 15 mg. The high degree of motor block tetracaine

produces may outlast the sensory blockade.

Cocaine

Cocaine is an ester of benzoic acid. It produces

topical anesthesia and vasoconstriction. In addition to its local anesthetic activity, cocaine causes

CNS stimulation that manifests initially as euphoria and sometimes dysphoria. This is followed by

poststimulatory depression. Cocaine’s cardiovascular effects are caused by the drug’s blocking the

uptake of catecholamines at adrenergic nerve terminals. This block can cause sympathetically mediated tachycardia, vasoconstriction leading to hypertension, myocardial ischemia, and dysrhythmias.

Administration of epinephrine or volatile anesthetics may sensitize the myocardium to the effects of

cocaine. Cocaine is metabolized by plasma cholinesterase.

Preparations of this drug consist of 4% to 10%

concentrations for topical anesthesia of the nose,

pharynx, and tracheobronchial tree.48 The usual

topical dose is 1 to 3 mg/kg.10

The fatal dose of cocaine has been approximated

at 1.2 g, although severe toxic effects have been

reported from doses as low as 20 mg.56 In wellpremedicated, extensively monitored, anesthetized
Perioperative Pain Management

313

patients presenting for cardiac surgery, no sympathomimetic effect was seen due to nasal topical

cocaine (1.5 mg/kg).57 Treatment of toxicity from

cocaine consists of the following protocol:

• Cardiotoxicity may be treated with esmolol

to control the heart rate.

• Labetalol offers hypertension control with

alpha and beta blockade.57

• Seizures from cocaine may respond to benzodiazepines.52

Amides

Lidocaine

Lidocaine was the first amide-derived local anesthetic. It has excellent tissue penetration, a rapid

onset, and intermediate duration (1–2 h). The addition of epinephrine improves the quality of the

block and decreases absorption from the site of

injection while also prolonging the duration of anesthesia.

Mepivacaine

Mepivacaine is similar to lidocaine in activity

and toxicity, and has an intermediate duration of

action. This drug is poorly metabolized by the fetal

liver, so therefore is infrequently used for obstetric

anesthesia. It is not effective topically.

Prilocaine

Prilocaine in doses higher than 600 mg may result in accumulation of the metabolite o-toluidine,

an oxidizing compound that converts hemoglobin

to methemoglobin. This methemoglobin production is reversed with methylene blue 1 to 2 mg/kg

administered intravenously.

Bupivacaine

Bupivacaine was developed from mepivacaine.

It has good separation of motor and sensory anesthesia. Bupivacaine has a slow onset, with a long

(3 h) duration of action. It is often used for postoperative analgesia because of the motor–sensory separation. Hepatic enzymes for bupivacaine metabolism are present in the fetus, so it may be used in

obstetrical anesthesia. Bupivacaine is commonly

used for subarachnoid anesthesia in hyperbaric

(0.75% bupivacaine with glucose) or isobaric (0.5%

bupivacaine) forms.

Etidocaine

Etidocaine is structurally similar to lidocaine.

It has a rapid onset of action and a prolonged

duration. Its motor block may outlast its sensory

block.

Ropivacaine

Ropivacaine is currently undergoing clinical trials. It has properties similar to bupivacaine but may

have less cardiotoxicity. Ropivacaine has a similar

pKa and protein-binding characteristics as bupivacaine. It is less lipid soluble than bupivacaine,

with similar onset and duration. It comes as 0.75%

to 1% concentrations. Ropivacaine has good separation of sensory and motor block.

MODE OF ADMINISTRATION OF ANALGESIC DRUGS

Under battlefield conditions, the postoperative care

of casualties should be as simple as possible. Whenever possible, casualties should take an active role in

their own care, thus limiting the amount of support

services needed. Monitored recovery areas are small

in wartime, compared with the number of patients

who will need operations. The task of the recoveryarea staff is to provide safe, adequate pain relief that

allows the casualty to be returned to an unmonitored

setting as quickly as possible.

Intramuscular and Intravenous Routes

The mainstay of postoperative pain relief will

probably be narcotics administered via the intravenous and intramuscular routes. Their mechanisms

of actions are well defined, they are easily administered, they are effective for acute pain, and their

effects can easily be reversed with an antagonist

like naloxone. Morphine and meperidine in particular are well-known drugs and most medical

personnel are familiar with the dosing regimens

(Tables 13-7 and 13-8).

Intravenous narcotics can also be delivered via a

PCA pump. The pump can be loaded with a supply

of narcotics that will last many hours, and, within

preset time limits (during which time the patient is

effectively locked out of the system), the patient can
Anesthesia and Perioperative Care of the Combat Casualty

314

TABLE 13-8

INTRAVENOUS MEDICATIONS

TABLE 13-7

INTRAMUSCULAR MEDICATIONS

Drug Dose (mg/kg) Peak Onset (min) Duration (h)

Narcotics

Morphine 0.05–0.10 45–90 3–6

Meperidine 0.25–0.50 60 2–4

Agonist–Antagonists

Butorphanol 0.015–0.030 45–90 3–4

Nalbuphine 0.05–0.10 45–90 3–6

Mixed Agonists

Dezocine 0.070–0.20 45–90 3–6

Nonsteroidal Antiinflammatory

Drugs

Ketorolac 30–60 mg 90 6–12

control the administration. Many authorities4,5,58,59

consider the pain relief from the pump to be superior to other forms of narcotics administration. The

added advantage of the PCA pump is that the patient feels a sense of control over his or her own

care.4 This administration technique would be very

useful in a field hospital. The drugs commonly

used in PCA pump are meperidine and morphine,

both in standard concentrations. Once the patient’s

PCA pump is programmed, it needs only to be

checked every 8 hours. The patient needs to be

observed every hour to check respiratory rate only.

This means that the personnel monitoring these

patients will have more time to function in other

capacities. For an adult, the starting dose can be 1

mg per dose for morphine and 5 mg per dose for

meperidine. The lockout interval should be 8 to 12

minutes. The dose can be increased as needed

according to the patient’s needs. If the clinical

picture mandates, a continuous infusion of narcotics can also be considered.

The usefulness of agonist–antagonists in the field

is limited. The major disadvantage of these medications is that the dose–response curves are usually

Drug Dose (mg/kg) Peak Onset (min) Duration (h)

Narcotics

Morphine 0.05–0.10 20 3–6

Fentanyl 0.001–0.002 10 1–3

Meperidine 0.25–0.50 20–30 2–4

Agonist–Antagonists

Butorphanol 0.007–0.015 20–30 3–4

Nalbuphine 0.05–0.10 20–30 3–6

Mixed Agonists

Dezocine 0.070–0.15 20–30 3–6
Perioperative Pain Management

315

shaped like an inverted U: the pain relief reaches a

plateau, then decreases with higher doses. With

lower doses, the agonist effects of the drugs predominate and the patient will obtain pain relief.

However, if the pain is intense and the patient

needs large doses of narcotic, the antagonist effect

of the drug tends to predominate and the patient

will not obtain relief.30 The next dilemma that the

medical officer encounters is that the agonist–antagonist opioid will also inhibit the activity of other

narcotics that would be used to alleviate the patient’s

pain. Thus, it would be very difficult to give the

correct amount of narcotics. Because of these problems, agonist–antagonist drugs would have limited

usefulness in the field for intravenous or intramuscular administration.

Another drug that could have a useful postoperative role in field hospitals is ketorolac, administered intramuscularly. This drug has been used

successfully for acute postoperative pain.60 Its advantages are that it is not a controlled substance and

it can be administered in conjunction with narcotics

for additive pain relief without additive side effects. Ketorolac would be a good adjunct to the

therapy of patients whose pain cannot be controlled

with large doses of narcotics. Once the patients are

tolerating oral intake, they can be switched to an

oral NSAID.

Epidural and Intrathecal Routes

Intrathecal or epidural delivery of narcotics

should be considered whenever possible. The advantage of these modes of administration is the

small amount of observation necessary for the

maintenance of good postoperative pain relief.

The prolonged and profound pain relief obtained

from medication delivered via these modes makes

them ideal for use in field hospitals. After epidural

or intrathecal administration, patient care includes

observation for respiratory depression and side

effects common to narcotics. Depending on the

type of injury, catheters can be placed in the epidural space for long-term narcotic administration. Not only will the patient be able to obtain

narcotics for pain relief, but if the patient needs

to be returned to the operating suite, the catheter

can be used to provide anesthesia for subsequent

operations.

After the narcotics have been administered, the

patient can return to a minimally monitored setting

for continued postoperative care. The patient can

receive either intermittent boluses of a long-acting

narcotic, or a continuous infusion of a shorter-acting substance (Table 13-9). The side effects of narcotics have been described above. The most dangerous side effect is respiratory depression but its

true incidence is difficult to determine. Current

studies indicate that it ranges from 1:32 to 1:260,

depending on the dose.6 The predisposing factors

to respiratory depression are advanced age, CNS

depression or concomitant systemic narcotic use,

increased intrathoracic pressure, and thoracic

extradural administration.6,36,37 The healthy, young

adults who comprise most of the military patient

population are at less potential risk for respiratory

depression. A well-tolerated treatment of narcotic

side effects is a naloxone infusion: the effects of

respiratory depression and the other side effects

can be reversed without also reversing the analgesic effects of the narcotics.

If the need for an epidural catheter is anticipated

for postoperative pain relief, and if the patient is to

remain at relative bed rest, then epidurally administered local anesthetics can be considered. Administering 0.125% to 0.25% solutions of bupivacaine

will not only increase the pain relief to the prescribed area, but will also increase the blood flow.

However, for this route to be of use, injury has to be

located in a nerve distribution that can be blocked

safely by an infusion of local anesthetic through an

epidural catheter.7

TABLE 13-9

POSTOPERATIVE OPIOID DOSES

Drug Intravenous Dose (mg) Epidural Dose (mg) Subarachnoid Dose (mg)

Morphine 5–10 2–5 0.20–0.50

Meperidine 50–100 30–50 10–20

Fentanyl 0.10–0.15 0.10–0.20 0.075–0.15
Anesthesia and Perioperative Care of the Combat Casualty

316

SUMMARY

Eliminating perioperative pain is justified not

only by medical ethics—the imperative to relieve

pain and alleviate suffering—but also because severe and unremitting pain can accentuate the potentially dangerous alterations in metabolism and

the function of various organs that are caused by

severe trauma. Foremost among the metabolic effects is hypermetabolism, leading to catabolism of

muscle protein and decreased lean body mass. Similarly, unrelieved pain from thoracic or upper-abdominal trauma may, by causing splinting of respiratory muscles, prevent normal pulmonary gas

exchange and clearance of tracheobronchial secretions. Thus, morbidity may be reduced by eliminating pain.

The neurological pathway by which we are made

aware of painful stimuli arising in peripheral tissue

begins in peripheral pain receptors, which connect

via peripheral nerves with ascending pathways that

arise in the dorsal horn cells of the spinal cord.

From here, information travels in the anterolateral

portion of the spinal cord through the brain stem

and hypothalamus to the cerebral cortex. The activity of the ascending tracts is modified by impulses

that descend from higher centers via descending

tracts that synapse with neurons in the dorsal horn.

Neurotransmitters are found along the neurological pathway—from substance P and histamine at

the peripheral pain receptors to serotonin and enkephalins in the CNS.

Therapeutic interventions that are likely to be

useful in treating combat casualties with painful

trauma are of two classes: those such as local anesthetics, which prevent transmission of impulses

along nerves either in the periphery or in proximity

to the spinal cord; and those that either interfere

with the synthesis and function of neurotransmitters or directly inhibit neurons in the CNS, which

transmit painful stimuli from the periphery. The

NSAIDs are examples of substances that alter neurotransmitter activity, while morphine and other

opiates, by acting on cells in the spinal cord, decrease traffic passing up the ascending tracts. Opiates also activate the descending inhibitor tracts

and act at sites along the neurological pathways for

pain in the brain stem and cerebrum.

The spectrum of pain-relieving interventions

 that are available to military anesthesia providers

ranges from orally administered NSAIDs, through

intravenous morphine, through regional or epidural blocks with local anesthetics, to epidural analgesia with opioids. Opioids have the advantage

of being both potent and, by not blocking sympathetic and motor pathways, selective. There is,

however, a risk of respiratory depression. Epidural block with a local anesthetic stops all afferent

nerve traffic, one consequence of which is peripheral vasodilation in the affected body parts,

which may give rise to potentially dangerous

hypotension.

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38. Hug CC, Murphy MR. Tissue redistribution of fentanyl and termination of its effects in rats. Anesthesiology.

1981;55:369–375.

39. Rutter DV, Skewers G, Morgan M. Extradural opioids for postoperative analgesia: A double-blinded comparison of pethidine, fentanyl, and morphine. Br J Anaesth. 1981;53:915–929.

40. Torda TA, Pybus DA. Comparison of four narcotics for extradural analgesia. Br J Anaesth. 1982;54:291–295.

41. Freye E. Cardiovascular effects of high dosage of fentanyl, meperidine and naloxone in dogs. Anesth Analg.

1974;53:40–47.

42. Gal TJ, DiFazio CA, Moscicki J. Analgesic and respiratory depressant activity of nalbuphine: A comparison with

morphine. Anesthesiology. 1982;57:367–374.

43. DiFazio CA. Pharmacology and narcotic analgesics. The Clinical Journal of Pain. 1989;5(suppl 1):S5–S7.

44. Prough DS, Roy R, Bumgarner J, Shannon G. Acute pulmonary edema in healthy teenagers following conservative doses of intravenous naloxone. Anesthesiology. 1984;60:485–486.

45. Partridge BL, Ward CF. Pulmonary edema following low-dose naloxone administration. Anesthesiology.

1986;65:709–710.

46. Ravel N, Schott U, Dahlstrom B, et al. Influence of naloxone infusion on analgesia and respiratory depression

following epidural morphine. Anesthesiology. 1986;64:194–201.

47. Thind GS, Wells CD, Wilkes RG. The effects of continuous intravenous naloxone on epidural morphine

analgesia. Anesthesia. 1986;41:582–585.

48. Jacob L. Pharmacology. 2nd ed. New York, NY: John Wiley; 1987.

49. Warfield C. Manual of Pain Management. Philadelphia, Pa: JB Lippincott; 1991.

50. Clark W. Goth’s Medical Pharmacology. St. Louis, Mo: Mosby–Year Book. 1992; 356–373.
Perioperative Pain Management

319

51. Ferrante FM. NSAIDs. In: Comprehensive Review of Pain Management. Richmond, Va: American Society of

Regional Anesthesia; 1994: 199–226.

52. Stoelting R, Miller R. Basics of Anesthesia. 3rd ed. New York, NY: Churchill Livingstone; 1994.

53. Raj P. Practical Management of Pain. 2nd ed. St. Louis, Mo: Mosby–Year Book; 1992.

54. DiFazio CA, Woods AM. Drugs commonly used for nerve blocking. Pharmacology of local anesthetics. In: Raj

PP, ed. Practical Management of Pain. St. Louis, Mo: Mosby–Year Book; 1992: 685–700.

55. McLaughlen S. Local anesthetics and the electrical properties of phospholipid bilayer membranes. In: Fink BR,

ed. Molecular Mechanisms of Anesthesia. New York, NY: Raven Press; 1975: 193–220.

56. Physicians’ Desk Reference. 48th ed. Montville, NJ: Medical Economics Data; 1994.

57. Barash P. Cocaine: Therapeutic Uses and Problems Anesthetizing the Abuser. Richmond, Va: ASA Annual Refresher

Course Lectures. October 19, 1991.

58. Hecker BR, Albert L. Patient-controlled analgesia: A randomized, prospective comparison between two

commercially available PCA pumps and conventional analgesia therapy for postoperative pain. Pain. 1988;35:115–

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59. Zacharias M, Pfeifer MV, Herbison P. Comparison of two methods of intravenous administration of morphine

for postoperative pain relief. Anaesth Intensive Care. 1990;18:205–209.

60. Brown CR, Moodie JE, Yee JP. Efficacy of intramuscular ketorolac and meperidine in pain following major oral

surgery. Clin Pharmacol Ther. 1988;43:161–165.
Transfusion Therapy

321

NORIG ELLISON, M.D.*

Chapter 14

TRANSFUSION THERAPY

INTRODUCTION

LOGISTICS

Collection, Distribution, and Administration of Blood

Component Therapy Versus Whole Blood

PURPOSES OF TRANSFUSION

Increase Oxygen-Carrying Capacity

Restore Hemostasis

POTENTIAL ADVERSE EFFECTS OF TRANSFUSION

Acid–Base Abnormalities

Hypothermia

Hyperkalemia and Hypocalcemia

Transmission of Infection

Immunosuppression

Hemolytic Transfusion Reactions

Allergic Reactions

Febrile Reactions

ALTERNATIVE SOLUTIONS FOR VOLUME REPLACEMENT

PRINCIPLES OF GOOD CIVILIAN TRANSFUSION PRACTICE

SUMMARY

*Professor of Anesthesia and Vice Chairman, Department of Anesthesia, University of Pennsylvania School of Medicine, 3400 Spruce Street,

Philadelphia, Pennsylvania 19104-4283
Anesthesia and Perioperative Care of the Combat Casualty

322

INTRODUCTION

In the foreword to the U.S. Army Medical

Department’s official history, Blood Program in

World War II, Lieutenant General Leonard D.

Heaton states:

If any single medical program can be credited with

the saving of countless lives in World War II and in

the Korean War, it was the prompt and liberal use

of whole blood.1(p ix)

Many physicians who served in the Korean and

Vietnam wars would certainly confirm that observation. We need only to observe the effect of a

rapid, multiple-unit transfusion via both femoral

veins in restoring a modicum of hemodynamic stability to an exsanguinated, seemingly pulseless, but

previously healthy young combat casualty to appreciate the validity of the American Red Cross

slogan that the gift of a unit of blood is, indeed, the

gift of life.

Earlier, Edward D. Churchill, in his World War II

memoir Surgeon to Soldiers, observed: “The goal of

resuscitation...is not solely to save life but to prepare for necessary surgery. This will in turn be

accompanied by further loss of blood.”2(p37) This

statement was written during the early days of the

North African campaign, when the policy called for

liberal use of plasma, not blood, because

(1) An interval of time is necessary [for cross-matching]. (2) Preservation can be for a relatively short

period [initially 8 days, later extended to 21 days]

and transportaion is difficult because of the need of

bulky and heavy apparatus for proper refrigeration. (3) The addition of red cells to the blood

stream is often undesirable, especially when large

quantities of blood are necessary (1,000 cc. or

more)....2(p43)

This third point is most astonishing in view of

recent combat and civilian experience and reflects

the body of knowledge against which Churchill

made his observation.

To study any clinical problem where many

variables are involved, a large number of patients are needed. Fortunately, the need for resuscitation involving a massive transfusion (defined as > 1.0 estimated blood volume [EBV]) is

rare in civilian practice; thus, three classic papers—one published in 1954 and based on the

Korean War experience,3 the other two published

in 1973 and 1974 and based on the Vietnam War

experience4,5—are frequently cited. The paper

from the Korean War described almost exclusive

use of low-titer, group O, Rh-positive “universal-donor” blood and warned that the use of

type-specific whole blood following the administration of universal-donor whole blood carried

with it the risk of hemolytic transfusion reaction.3 It may be a reflection of the increasing

sophistication of the U.S. Army Medical Department that during the Vietnam War, type-specific

blood was usually used without undue risk of

hemolytic transfusion reaction at field and evacuation hospitals. Clearing companies and forward surgical hospitals continued to use group

O, low-titer, Rh(d) whole blood, and patients

who received more than four such units continued to receive this type on evacuation until laboratory results demonstrated that the administration of type-specific red blood cells (RBCs) would

not produce a hemolytic transfusion reaction.6,7

Table 14-1 lists the 14 issues addressed in either

or both papers that describe transfusion practice

during the Vietnam War.4,5 The marked similarity

in the problems perceived and the solutions to them

is not surprising. In fact, except for the issue of

coagulopathy in relation to volume of blood transfused, the conclusions in the two papers are essentially identical.

LOGISTICS

One of the major problems facing the severely

traumatized patient in need of massive transfusion

is logistical, which includes obtaining and transporting whole blood and blood components to the

treatment center, as well as securing sufficient largebore intravenous lines to permit rapid infusion.

Collection, Distribution, and Administration of

Blood

The problems unique to a combat situation such

as existed in Vietnam include highly variable demand rates. From fewer than 100 units per month in
Transfusion Therapy

323

TABLE 14-1

PROBLEMS ASSOCIATED WITH MASSIVE TRANSFUSION

Discussed

in this Discussed Discussed

Chapter? in Collins?1 in Miller?2

Acid-base balance Yes Yes Yes

Altered 2,3 diphosphoglycerate No Yes No

Citrate toxicity Yes Yes Yes

Coagulation Yes Yes Yes

Denatured protein No Yes No

Mathematics of blood replacement Yes Yes No

New additives No Yes No

Other sources of blood Yes No Yes

Plasticizers No Yes No

Posttransfusion hepatitis Yes No Yes

Potassium, ammonia, phosphate Yes Yes Yes

Pulmonary effects, microemboli Yes Yes Yes

Temperature regulation Yes Yes Yes

Vasoactive substances No Yes No

Data sources: (1) Collins JA. Problems associated with the massive transfusion of stored blood. Surgery. 1974;75:274–295. (2) Miller

RD. Complications of massive blood transfusions. Anesthesiology. 1973;39:82–93.

1965, the demand peaked in February 1969 at 38,000

units per month (Figure 14-1), with very long supply lines.6 To ensure that blood will arrive in country as soon as possible after collection, some of thisblood was actually processed while being flown to

Vietnam from the 42 donor centers set up in the

Fig. 14-1. Units of blood used in South Vietnam, January 1965 through December 1970. Reprinted from Neel S. Medical

Support of the US Army in Vietnam, 1965–1970. Washington, DC: Department of the Army; 1973: 115.

40,000

30,000

20,000

10,000

Units of Blood Transfused

1965 1966 1967 1968 1969 1970
Anesthesia and Perioperative Care of the Combat Casualty

324

United States and Japan. Nevertheless, blood was

approximately 7 days old when received in Vietnam, and further time-consuming shipment forward was required.

Such combat-unique situations do not exist in a

civilian setting. However, the supply-to-demand

ratio for blood remains perilously thin. An editorial

published in 1975 stated that only 5% of the population provided more than 95% of the blood administered in the United States and wishfully surmised

that if the number of donors could be doubled, then

the problem of blood shortages would become history.8 In the interim, improved technical capabilities have (a) almost doubled the number of units

collected, (b) increased utilization by extending shelf

life from 21 to 42 days, and (c) increased fractionation nationwide, thus permitting the blood supply

to be extended even further. Nevertheless, the

supply of blood barely meets the demand. Why?

There are three reasons: (1) the development of

more invasive procedures such as liver transplants

and radical cancer surgery, and (2) the use of highly

aggressive treatment protocols (especially those

used in oncology patients), both of which require

more platelets to prevent iatrogenic hemorrhage;

and (3) more recently, the irrational fear in a significant portion of the potential donor population that

the act of donating blood carries with it a risk of

contracting blood-borne infectious diseases such as

acquired immunodeficiency syndrome (AIDS).

To avoid a hemolytic transfusion reaction, a system of patient-to-specimen identification and marriage is essential, especially so in mass casualty

situations. The most common cause of death due to

hemolytic transfusion reaction in peacetime is clerical error that occurs outside the blood bank and

results in a patient’s receiving an ABO-incompatible unit of blood.9 In trauma centers, the assignment of a specific “trauma number” to each patient

immediately on arrival has proven an effective way

to begin a patient-identification system.

Although the Seldinger technique for inserting

large catheters into blood vessels was originally

described in 1951, the technique was not commonly

used outside angiographic suites and cardiac catheterization laboratories until the mid-1970s,10 and

surgical cutdowns on the saphenous, femoral, or

antecubital veins were used during the Vietnam

War to provide adequate venous access to facilitate

rapid, large-volume transfusion. In civilian trauma

centers today, the subclavian and internal or external jugular veins are the vessels most commonly

used, and the Seldinger technique is employed to

insert large-bore catheters. Also, the inflatable pressure bags that were formerly employed have largely

been replaced by rapid-infusion systems, a by-product of the heart-lung machine. Because the American College of Surgeons’ Advanced Trauma Life

Support (ATLS) practice guidelines are used by the

military’s deployable medical facilities, fluid resuscitation of combat casualties will most commonly

involve percutaneous access through an antecubital

vein or an extremity cutdown rather than a central

venous catheterization.

Component Therapy Versus Whole Blood

The three classic wartime studies3–5 dealt with

the use of whole blood. Currently in the United

States, however, more than 80% of blood is fractionated at the time of collection. This may not leave

sufficient whole blood for use in trauma and other

instances of massive blood loss where many clinicians believe whole blood is desirable, if not essential. The issue is one that has plagued the relationship between anesthesiologists and blood-bank

specialists for some time, as the following comments illustrate:

There will be little variation in response from the

blood bank: You will ask for whole blood, and they

will send you packed cells, even though people

bleed only whole blood,... you will be stuck with

the time-consuming reconstitution of each cold

sludgy unit.11(p94)

. . . .

I believe that in an active general-hospital practice,

half the transfusions should be given as whole

blood. A greater use of cells perpetuates the make

work cycle and at least doubles the cost to the

patient.12(p1411)

The principal arguments for the use of component therapy are (1) it permits specific, goal-directed therapy, and (2) at the same time, each unit of

blood can be used to treat several patients. In

particular, if Factor VIII is removed to treat patients

with hemophilia, and if platelets are removed to

permit more aggressive chemotherapy in oncology

patients, a by-product will be packed RBCs; many

surgical patients are suitable candidates to receive

this by-product, not just those in whom volume

overload is a consideration. One investigator13 has

suggested that if fewer than four units are needed,

RBCs diluted with crystalloid or colloid solutions

will suffice; if more than four are required, whole

blood would be preferred. Others14have approached

this problem differently: after they remove the platelets and cryoprecipitate from a unit of whole blood,
Transfusion Therapy

325

Allowable blood loss = • EBV

Hbinitial

they return the remaining plasma to the RBCs, producing modified whole blood. The effectiveness of

this product in treating trauma patients without

increasing hemostatic problems has been demonstrated, and more widespread use of modified whole

blood would seem indicated.

PURPOSES OF TRANSFUSION

There are two major purposes for transfusion

therapy: (1) to improve the oxygen-carrying capacity of the cardiovascular system and (2) to restore

hemostasis by increasing coagulation factor and

platelet concentrations to hemostatic levels.

Increase Oxygen-Carrying Capacity

Oxygen transport is a prime function of the cardiopulmonary system. There are a number of factors that are determinants of oxygen transport (eg,

the RBC mass and the circulating blood volume).

The body’s defense mechanism to maintain a normal intravascular volume in the presence of blood

loss will mobilize interstitial fluid and then shift it

into the intravascular space, but this process takes

hours. In contrast, the body’s attempt to maintain

cardiac output (ie, constriction of systemic venules

and small veins and, when blood loss continues,

constriction of the vascular sphincters in circulatory beds of skin, skeletal muscle, kidney, and

splanchnic viscera) occurs within 60 to 120 seconds of an acute hemorrhage. The maintenance

of cardiac output is mediated by the adrenergic

system and circulating catecholamines, and by

the renin-angiotensin system and the secretion of

vasopressin. As a result, hemoglobin levels will

remain falsely high if volume-for-volume replacement is not carried out on an ongoing basis.

Preservation of blood flow to the heart and brain,

two organs capable of regulating their own flow

over a wide range of arterial pressure, will be

preserved until the loss exceeds the ability to

compensate.15

Allowable Blood Loss and Normovolemia

Although circulating blood volume is lost during hemorrhage, increased venous tone and augmented contractility may bring about an increase

in cardiac output, which will make possible maintenance of normal oxygen transport. Therefore,

volume replacement is not a reason for blood or

blood-component transfusion if a compensatory

increase in cardiac output has resulted in maintenance of normal oxygen delivery. Indeed, it is a

common practice in elective surgery to permit

patients to lose blood down to a predetermined

hemoglobin level before blood transfusion begins, based on the formula

TABLE 14-2

ESTIMATED BLOOD VOLUME, BASED ON

BODY WEIGHT AND HABITUS

Blood Volume as

% of Body Weight

Body

Habitus Female Male

Obese 5.5 6.0

Asthenic 6.0 6.5

Lean 6.5 7.0

Muscular 7.0 7.5

Hbinitial – Hbtarget

where Hbinitial represents the hemoglobin at the

start of surgery, Hbtarget represents the target hemoglobin level at which point blood transfusion will

be started, and EBV represents the estimated blood

volume.16

A rough estimation of EBV may be calculated by

multiplying body weight by the figures given in

Table 14-2, which also incorporate corrections that

need to be made for gender and body habitus. This

allowable blood loss formula has a built-in safety

factor, in that each successive milliliter of blood lost

will be more dilute than the one lost before.

In using this formula, the maintenance of

normovolemia by replacing the ongoing blood loss

on a 1:1 basis with colloid solution, or a 1:3 basis

with crystalloid solution, is assumed and is crucial.

Failure to replace ongoing loss will result in

hypovolemia, which is followed quickly by hypotension and tachycardia. In an acute trauma patient

in whom bleeding has been ongoing in the absence

of significant asanguineous fluid replacement (as is

common with combat casualties), neither the measured hemoglobin level nor the blood volume estimated from Table 14-2 will reflect the actual circu-
Anesthesia and Perioperative Care of the Combat Casualty

326

Coagulation Remaining After Minimal Level

Factor 21-Day Storage (%) for Hemostasis (%)

I 99 50–100

II 93 20–40

V 51* 10–15

VII 82* 5–10

VIII 29† 10–40

IX 95 10–40

X 89* 10–15

XI 88* 10–40

XII 100 —

XIII 100 1–5

lating RBC mass. Thus, in contrast to the practice in

elective operations, intentional hemodilution in a

trauma patient is probably ill advised.

Hemoglobin Level and the “Transfusion Trigger”

Far more controversial than the need to maintain

normovolemia is the issue of what constitutes a safe

lower level of hemoglobin. It was formerly a common practice to use 10.0 g of hemoglobin per deciliter of blood as the minimum acceptable hemoglobin level. Below this level, patients would be

transfused before anesthesia was induced. At this

level, if the patient was already anesthetized and

had lost sufficient blood, blood transfusion would

begin with simultaneous replacement of crystalloid

or colloid solution to reach a hemoglobin level of

10.0 g/dL. This practice frequently created conflict

between anesthesiologists and surgeons, as the following statement implies:

Anesthesia needs a careful reevaluation of the minimum hemoglobin level below which the administration of anesthesia is not safe. It is not the same for

all patients nor for all procedures. We request intelligent individualization.17(p302

Today, especially in the acutely traumatized patient, there is no minimum acceptable level, no

“magic” number. The 1988 National Institutes of

Health Consensus Development Conference on

Perioperative Red Blood Cells Transfusion18

specifically recommended a decrease in the

“transfusion trigger” (ie, the point that must be

reached before a transfusion is necessary) from 10.0

g/dL, but did not set a lower limit. A 70-kg

man will consume approximately 250 mL of oxygen

per minute, and oxygen delivery is approximately

1,000 mL/min, resulting in an oxygen-extraction

ratio of 25%. This ratio reflects only part of the

reserves the body can call on when oxygen consumption increases or the hemoglobin level decreases. A combination of increased oxygen extraction and cardiac output, as well as preservation

of blood flow to vital organs, will provide adequate

oxygen delivery in the presence of profound

anemia. A hematocrit of 0.10 (equivalent to a hemoglobin level of 3.3 g/dL) and an oxygen extraction

ratio of 50% have been suggested19 as the crucial

points below which survival is questionable. An

earlier researcher20 had kept anesthetized young

pigs alive for 45 minutes with hematocrits of 0.004

by administering 100% oxygen at 3 atm in a hyperbaric chamber.

While it is doubtful that clinicians will ever have

to deal with either of these values, hemoglobin

levels of 7 to 9 g/dL are commonly used today as the

point that must be reached—in the stable posttrauma

patient—before allogenic blood will be administered. Two groups of patients have forced clinicians to alter their transfusion practices: those with

renal failure, and members of the religious group

Jehovah’s Witnesses. Considerable clinical experience with both groups has repeatedly demonstrated

that patients can tolerate much lower hemoglobin

levels without either impaired wound healing or

delayed convalescence.

Restore Hemostasis

Effective hemostasis depends on the triad of vascular integrity, an adequate number of functional

platelets, and a minimal level of each coagulation

factor. A defect in vascular integrity is the common

precipitating event resulting in the need for blood

transfusion in any trauma or other surgical patient,

TABLE 14-3

COAGULATION FACTOR LEVELS AT 21 DAYS

OF STORAGE AS FRESH FROZEN PLASMA

AND THE MINIMAL HEMOSTATIC LEVELS

*Decrease is statistically but not clinically significant

†Decrease is significant both statistically and clinically

Data sources: (1) Hondow JA, Russell WJ, Duncan BM, et al. The

stability of coagulation factors in stored blood. Aust N Z J Surg.

1982;52:265–269. (2) Pisciott PT, ed. Blood Transfusion Therapy: A

Physician Handbook. 3rd ed. Arlington, Va: American Association of Blood Banks; 1989.
Transfusion Therapy

327

1. mixing is instantaneous and complete,

2. initial blood volume equals final blood

volume,

3. the recipient is essentially a closed system

(ie, the patient is no longer continuing to

lose blood), and

4. the transfused blood is uniform.

Obviously, the idealized situation never exists; in

the more common trauma situation (ie, patients B

or C in Figure 14-2), patients are received in a

hypovolemic state and must be transfused back to

their original blood volume.

Platelets and Dilutional Thrombocytopenia

In contrast to the hemostatic efficiency of the

coagulation factors, which is maintained even at

low temperatures, the hemostatic efficiency of platelets declines rapidly below a critically low platelet

count. For this reason, a dilutional thrombocytopenia is the most common cause of bleeding in patients who receive a massive transfusion. This is

true whether the patient receives whole blood,

modified whole blood, or RBCs.14 In 21 combat

casualties who received more than 15 units of blood

(described in one of the two studies done during the

Vietnam War era),4 the researchers correlated how

closely the decrease in platelets approximates a

washout equation—as if the units administered were

platelet-free. In four casualties whose MVB did not

5 10 15 20 25

100

90

80

30

40

50

60

20

10

70

Percentage of Original Blood Remaining

Fig. 14-2. Percentage of original blood

remaining in each of three hypothetical

recipients, all beginning and ending with

a blood volume of 5 L, assuming that

each unit of blood contains 500 mL, and

using formulas and assumptions for continuous exchange described in text. Patient A remains normovolemic throughout. Patients B and C sustain a loss of one

half their normal blood volume before

transfusion begins. In Patient B, this loss

is replaced immediately; subsequent

hemorrhage and transfusion occur with

a normal blood volume. In Patient C, the

initial loss is replaced only after hemorrhage has stopped. Reprinted with permission from Collins JA. Problems associated with the massive transfusion of

stored blood. Surgery. 1974;75:277.

Patient A

Patient B

Patient C

and restoration of vascular integrity is primarily a

surgical responsibility. However, no matter how

meticulous a surgeon is in meeting that responsibility, patients will continue to bleed if an adequate

number of normally functioning platelets and a

minimal level of the 11 coagulation factors are not

present. Microvascular bleeding (MVB) is the term

used to describe the diffuse hemorrhagic syndrome,

which is not surgically correctable.

The minimal levels of platelets and coagulation

factors necessary for effective hemostasis, and the

levels present after 21 days of storage in a blood bank,

are shown in Table 14-3. Clearly, with the possible

exception of factor VIII, a deficiency of which produces the clinical syndrome of hemophilia A, none of

the coagulation factors will decay to clinically significant levels, although a statistically significant decay occurs in the levels of factors V, VII, X, and XI.21

The concentrations of platelets and coagulation

factors are peculiarly sensitive to dilutional effects

arising from volume replacement—with either

packed RBCs or asanguineous fluid. The effect of

dilution is best understood when viewed in terms of

the mathematics of blood replacement, which are

illustrated in Figure 14-2. In the controlled and

idealized situation, where replacement volume

matches ongoing blood loss, replacement of 1.0

EBV will allow 36.8% of the original blood, including platelets and coagulation factors, to remain.5

This calculation is based on four assumptions that

constitute the ideal:

Number of Units Transfused

30
Anesthesia and Perioperative Care of the Combat Casualty

328

decrease after the administration of fresh frozen

plasma (FFP), the administration of 3 to 4 units of

fresh whole blood resulted in a marked increase in

platelet count and a decrease in bleeding.4 The

other study from the Vietnam War5 did not find so

strict a relation between volume of blood transfused and MVB; these researchers concluded that,

in general, the most seriously injured casualties

exhibited the most abnormal coagulation patterns,

and earlier, complete resuscitation prevented the

bleeding complications.

Fresh Frozen Plasma

When only RBCs are administered, reconstitution of the RBCs with crystalloid or colloid solutions other than FFP may accelerate the decrease in

the levels of coagulation factors and contribute to

MVB.22 However, no formula for units of FFP per

units of RBC transfused has been demonstrated to

be effective in preventing MVB, nor are routine

coagulation tests useful as predictors of MVB and

the need for FFP.23 Indeed, in massive transfusion,

an abnormality of these tests may be considered the

norm, and test results must be correlated with the

clinical picture to determine whether the administration of platelets or coagulation factors is required.24 Researchers using modified whole blood

found that platelet counts lower than 50 • 109/L or

fibrinogen levels lower than 80 mg/dL were associated with increased bleeding. They also echoed the

call for whole blood to treat patients who require

massive transfusion.25

The 1984 National Institutes of Health Consensus Development Conference on Fresh Frozen

Plasma listed six indications and four nonindications

for the use of FFP (Exhibit 14-1). In particular, the

Consensus Development Conference strongly condemned the use of prophylactic FFP in patients who

require massive transfusion, while at the same time

acknowledging that

[t]he use of fresh frozen plasma in massive blood

transfusion, for which there is less credible evidence of efficacy, appears to have increased in

frequency, possibly due in part to the relative unavailability of whole blood.26(p552)

If FFP is to be used in these patients, no absolute

rule can be proposed to govern its administration.

A review article discussing the use of FFP in patients with hepatic disease and who have massive

blood transfusion suggested only broad general

guidelines (Exhibit 14-2).27

EXHIBIT 14-1

NATIONAL INSTITUTES OF HEALTH

CONSENSUS DEVELOPMENT

CONFERENCE RECOMMENDATIONS

ON FRESH FROZEN PLASMA

Indications for Fresh Frozen Plasma

1. Replacement of factors II, V, VII, X, and XI

(concentrates are available for factors VIII

and IX)

2. Neutralization of coumarin intercoagulation

3. Massive blood transfusion

4. Source of antithrombin III

5. Treatment of immune deficiencies in infants

due to severe protein-losing enteropathy

when total parenteral nutrition is ineffective

6. Treatment of thrombotic thrombocytopenic

purpura

Nonindications for Fresh Frozen Plasma

1. Volume expansion

2. Nutritional supplement

3. Postcardiopulmonary bypass prophylaxis

4. Massive blood transfusion prophylaxis

Source: Consensus Development Conference. Fresh-frozen

plasma: Indications and risks. JAMA. 1985;253:551–553.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC)

is a relatively recently recognized entity, first

appearing in Index Medicus in 1973, but one for

which numerous etiologies have long produced

recognizable clinical syndromes—ranging from

the bleeding seen in women with abruptio placenta

to that which can follow a hemolytic transfusion

reaction. Treatment of DIC requires treatment of

the primary cause as well as restoration of an effective hemostatic process. The triad of decreased

platelet count, increased prothrombin time, and

decreased fibrinogen in the absence of transfusion

can be considered diagnostic for DIC. If only two of

the three are present, an increase in fibrin split

products is necessary. Indeed, in the appropriate

clinical setting, a decrease in platelet count and

fibrinogen is sufficient to make the diagnosis.24

Shock and acidosis are commonly seen in the trauma

patient and are also potential contributors to initiating DIC.
Transfusion Therapy

329

EXHIBIT 14-2

GUIDELINES FOR USING FRESH FROZEN PLASMA IN MASSIVE TRANSFUSION

1. The initial volume required for significant effect on the coagulation status needs to be large and administered

rapidly (ie, 600–2,000 mL over 1–2 h).

2. There is probably no indication for administering fresh frozen plasma (FFP) to patients with severe liver

disease and abnormal levels of coagulation factors who are not actively bleeding or facing a hemostatic

challenge (any surgical procedure is considered to be a hemostatic challenge).

3. FFP is not likely to help trauma and postoperative patients who are not actively bleeding or patients

undergoing elective operations with moderate blood replacement unassociated with shock.

4. FFP may help control abnormal bleeding in trauma patients receiving massive transfusion. Large volumes,

rapidly administered, are necessary. Particular attention to platelet levels is more important because

dilutional thrombocytopenia is a more common cause of bleeding in this setting.

5. Although there is no shortage of set schedules for administration of FFP, most are unreferenced and

anecdotal, and not one regimen has proven effective.

 6. Rigid use of the activated partial thromboplastin time or prothrombin time to anticipate the probability of

beneficial effect of FFP is not justified. Although these tests may help in individual cases, their poor

predictive value for the development of abnormal bleeding diminishes their usefulness.

Source: Braunstein AH, Oberman HA. Transfusion of plasma components. Transfusion. 1984;24:281–285.

from the defect will limit loss. Furthermore, as

blood loss continues without replacement, blood

pressure will progressively decrease, thereby minimizing or even halting blood loss. Anesthesiologists can best contribute to the maintenance of vascular integrity by providing adequate anesthesia to

avoid hypertension and, where appropriate, using

vasoactive agents such as sodium nitroprusside to

decrease blood loss by inducing hypotension.

Surgical Hemostasis

The third element in effective hemostasis, vascular integrity, is usually ignored or relegated to the

domain of the surgeon. However, several physiological defense mechanisms will limit blood loss in

the body’s attempt to maintain homeostasis. Initially, vasoconstriction to decrease the size of the

defect and anastomotic dilation to shunt blood away

POTENTIAL ADVERSE EFFECTS OF TRANSFUSION

Acid–Base Abnormalities

Patients who require massive blood transfusion

become acidotic for two reasons23:

1. The need for a large-volume transfusion

indicates a massive blood loss, which is

consistently associated with decreased

blood pressure and perfusion, which in turn

may lead to anaerobic metabolism and increasing acidosis.

2. The preservative solutions in which blood

is collected are all acidotic, and blood pH at

the time of collection will be 7.16. Continued carbon dioxide and lactic acid production without means of escape for the former

will decrease the pH to 6.87 at 21 days and

6.73 at 35 days.

Previously, some authorities recommended giving bicarbonate empirically (eg, 44.6 mEq for every

five units of whole blood). However, the need for

bicarbonate cannot be based on any empirical formula.28,29 If transfusion in any volume restores hemodynamic stability, then there will be no need for

bicarbonate. In the patient who remains in shock,

anaerobic metabolism will persist and acidosis will

worsen. In such patients, the administration of

bicarbonate is better determined by an arterial blood

gas analysis than by an empirical formula.
Anesthesia and Perioperative Care of the Combat Casualty

330

Hypothermia

Blood is stored at 4°C, and approximately 15 kcal

are required to raise each unit of whole blood to

37°C, approximately one half that needed for one

unit of RBCs.5 This is not a problem when 1 to 3

units are administered over several hours.23 However, in massive transfusion, marked hypothermia

can occur if the blood is not warmed. Except for

possibly decreasing oxygen demand, little good can

result from hypothermia (Exhibit 14-3). Even the

beneficial effects of decreased oxygen demand are

offset by the increased oxygen demand that results

from shivering, which can occur with a decrease of

0.5°C to 1.0°C in esophageal temperature.

Warming of blood is best accomplished by means

of a high-capacity fluid warmer. There is no shortage of blood warmers available, and their use can

avoid or markedly ameliorate the problem of hypothermia in the patient receiving a massive transfusion.30 This problem is best treated prophylactically.

Hyperkalemia and Hypocalcemia

While blood is stored, potassium concentration

progressively increases in plasma as potassium

leaches out of the cells, increasing in concentration

from 12 mEq/L at 7 days to more than 32 mEq/L at

21 days. This rarely produced a clinical problem in

the past, because the blood would have to have been

administered at a rate greater than 120 mL/min—a

rate that was rarely achieved before rapid-transfusion devices were developed. However, cardiac

arrest was recently reported in a patient who received such a transfusion; the rate peaked at 420

mL/min just prior to the arrest. Potassium was 10.7

mEq/L just prior to the arrest and 12.6 mEq/L

immediately after.31

While the development of hyperkalemia is not a

problem in most transfusions, electrocardiographic

signs of hyperkalemia, particularly high-peaked T

waves and a shortened QT interval, occur initially

(serum potassium level 6.0 mEq/L). At serum potassium levels higher than 6.5 mEq/L, the QRS

complex widens, simulating left bundle branch

block, and the PR interval increases at levels higher

than 7.0 mEq/L. Potassium levels higher than 10 to

12 mEq/L produce ventricular fibrillation or

asystole. Prophylactic treatment with calcium is

not recommended. However, in response to electrocardiographic changes, calcium administration

is certainly indicated. Preventive measures include

using fresh blood (ie, < 5 d old), rarely a practical

solution, or washing the RBCs with saline in a cell

saver just before transfusion.31 The latter has the

potential of decreasing potassium once potassium

equilibrates sufficiently to produce hypokalemia,

which has its own dysrhythmic problems.

As blood is collected in donor bags, chelation of

calcium prevents the formation of clots. This has

EXHIBIT 14-3

ADVERSE EFFECTS OF HYPOTHERMIA

1. Metabolism is impaired:

• citrate and lactate: may lead to hypocalcemia and acidosis.

• narcotics and anesthetic agents: result in prolonged half-life and delayed awakening, especially

undesirable in anesthesia.

2. Release of potassium from intracellular space is promoted. This potassium could be additive with that

released in an acidotic state; increased potassium will impair cardiac function.

3. The affinity of hemoglobin for oxygen is increased, thereby decreasing the availability of oxygen stores

at the tissue level.

4. Increased risk of dysrhythmias, especially at temperatures < 30°C. Theoretically, rapid transfusion

through large central catheters may preferentially cool the myocarcium, resulting in dysrhythmias at

body temperatures well above < 30°C.

5. Shivering will increase oxygen demands, producing an increase of oxygen demand and cardiac output.

Source: Collins JA. Problems associated with the massive transfusion of stored blood. Surgery. 1974;75:274–295.
Transfusion Therapy

331

been the fundamental principle on which anticoagulation in transfusion medicine is based,

whether the anticoagulant is acid citrate dextrose,

citrate phosphate dextrose (shelf life 3 wk), or an

adenine-containing anticoagulant such as citrate

phosphate dextrose–adenine 1 (CPDA-1, shelf life 5

wk), or adenine solution number 1 (ADSOL, manufactured by Baxter Healthcare Corp, Roundlake, Ill;

shelf life 6 wk). ADSOL is the chemical preservative

most frequently used by the American Red Cross.

The U.S. military continues to use CPDA-1. Blood

prepared with the latter has a slight logistical advantage because it has a hematocrit of 0.80; the

hematocrit of ADSOL-preserved blood is 0.60. Because citrate is always present in excess of the ionized calcium in the unit collected to ensure adequate anticoagulation, the administration of a unit

of whole blood or plasma may decrease the ionized

calcium in the plasma. This possibility prompted a

recommendation to administer ionized calcium on

an empirical basis. However, the increased citrate

toxicity level is extremely transient because of rapid

hepatic metabolism. Indeed, J. P. Bunker’s32 original conclusion that citrate toxicity was a potential

problem in patients with impaired hepatic function

(made in 1955, a decade before the advent of the

ionized calcium electrode) is explained by that patient population’s inability to metabolize citrate

rapidly. The conclusion remains valid today. The

inverse relationship between citrate and ionized

calcium levels, as well as the transient nature of any

depression on ionized calcium levels after calcium

is discontinued, have been shown clearly.33

Therefore, the anesthesiologist should remember that routine calcium administration is not indicated. If electrocardiographic signs of hypocalcemia

develop, manifested by widening of the QRS complex, then calcium administration is indicated. The

clinical manifestation of hypocalcemia is, in fact,

decreased myocardial contractility, not a hemorrhagic diathesis. Both hemodynamics and the electrical activity of the heart will usually improve

promptly as citrate levels decrease. Calcium administration is rarely required.

Transmission of Infection

In 1943, B. B. Beeson34 reported seven cases of

jaundice occurring 1 to 7 months after blood transfusion, the first recognition that infection could be

transmitted via blood products. In 1975, the U.S.

Food and Drug Administration began requiring

that all deaths associated with blood transfusions

be reported; during the next decade, 355 deaths

were so implicated. Of these deaths, 97 (27.3%)

were due to disease transmission, including 3 related to AIDS.35 Because AIDS was only beginning

to surface as a transfusion-associated disease by

1985, with the first death reported in the literature

during 1983, the percentage of transfusion-associated AIDS deaths will undoubtedly increase.

Although viral, bacterial, and parasitic diseases

can all be transmitted by blood transfusion, the

transmission of viral diseases is the major problem.

Blood from donors with undetected infections can

unintentionally be collected for transfusion in the

following circumstances:

1. The donor is either an asymptomatic carrier, or has a clinically inapparent disease,

or is in the prodromal stage of infection.

Otherwise, the potential donor would have

been rejected from donating blood on the

basis of the history or physical examination.

2. The disease is in the early stage, where

serologic markers of infection have not developed (the “window”), or the disease is

one for which routine screening is not yet

available.

Viral Diseases

Hepatitis. The demonstration that blood obtained commercially was associated with higher

incidences of posttransfusion hepatitis (PTH) than

that collected from voluntary donors provided the

impetus for an all-volunteer blood-donor system.

This was the first positive step to decrease the

incidence of PTH. Two studies,36,37 published 7

years apart, on patients who had cardiac surgery at

the National Institutes of Health, Bethesda, Maryland, are revealing. The first, published in 1965, in

which the patients had received large volumes of

allogenic blood during the early 1960s, demonstrated that patients who receive primarily commercial blood developed either icteric or nonicteric

hepatitis in 50% of the cases.36 In the second, published in 1972, in which the patients received

exclusively volunteer blood that was negative for

hepatitis A–antigen, the incidence of PTH dropped

to 7.1%.37

Even in the 1990s, PTH, which produces long- as

well as short-term morbidity and mortality, remains

the most common infection associated with allogenic

blood transfusion. The identified viruses are hepa-
Anesthesia and Perioperative Care of the Combat Casualty

332

titis A, B, C (the most recently identified), and delta.

During the mid-1960s, two groups of researchers

contributed significantly to our knowledge of hepatitis. Saul Krugman and associates38 clearly distinguished two types of hepatitis, infectious and serum, on the basis of incubation period, history, and

duration. At the same time, B. S. Blumberg and

associates39 identified the antigen responsible for

serum hepatitis, the so-called “Australian antigen,”

which originally was found in an Australian aborigine. This antigen is now known to be the

unassembled viral coat or surface antigen, HBsAg.

Hepatitis A (infectious hepatitis), caused by the

hepatitis A virus (HAV), is a rare cause of PTH for

three reasons: (1) there is only a brief (7- to 10-d)

viremia during the prodromal phase when patients

would be acceptable donors, (2) passively transfused anti-HAV antibodies from other transfused

units would prevent HAV from infecting a recipient, and (3) there is no carrier state for HAV.

Hepatitis B, caused by the hepatitis B virus (HBV),

remains a source of PTH with an estimated frequency of 1:200 to 1:300, despite the existence since

1971 of a serologic test.18 Administering blood in

emergencies without testing, or collecting blood

during the window before serologic markers develop, or both, explain the continued production of

PTH by HBV. Of all patients who develop HBV,

90% will have a self-limited course, with the majority being asymptomatic (70% nonicteric); 5% to 10%

will go on to a chronic state; and 1% will have a

fulminant form of hepatitis with a mortality higher

than 50%. Of the 10% who develop a chronic state,

one half will evidence one of the chronic forms

of hepatitis and the remainder will become

asymptomatic carriers.40 This last cohort is the

group without symptoms or history of hepatitis

whose blood would transmit HBV were it not for

the hepatitis B surgace antigen (HBsAg) test. Two

other HBV antigens have been identified: the inner

protein core (HBc) and the e antigen (HBeAg), which

is a free protein in serum. The development of

antibody to HBsAg indicates that immunity to HBV

has developed and resolution of the acute infection

is occurring, while failure to develop anti-HBs and

the persistence of detectable anti-HBc and HBsAg

indicate chronic infection.

Hepatitis C, caused by the hepatitis C virus (HCV),

has now been identified, having previously been

known by the unwieldy term non-A, non-B (NANB)

hepatitis, and it is quite likely that some as-yetundetermined portion of NANB hepatitis is not due

to HCV.41 This virus has a shorter incubation period

than HBV (35–70 d) and a milder initial course, with

75% of patients being nonicteric; but 50% of patients

will develop a chronic state and 10% will progress

to cirrhosis.42

Evidence for the role of blood transfusion in the

induction of chronic liver disease and the inability

to develop a specific NANB hepatitis assay

prompted the adoption of surrogate tests for the

detection of NANB hepatitis carriers. These were

serum alanine aminotransferase and anti-HBc. It

was estimated that these surrogate markers would

reduce the incidence of NANB hepatitis by 50%,

based on retrospective studies conducted at the

National Institutes of Health.40 The effect of the

development of a specific assay of HCV is unresolved, as is whether it will negate the use of surrogate tests.

Human Immunodeficiency Virus. Human immunodeficiency virus (HIV) is a ribonucleic acid (RNA)

retrovirus first reported to be transmitted by transfusion when a 20-month-old child, who had received blood products from 19 donors in the first

month of life during exchange transfusions to treat

hemolytic disease of the newborn, developed AIDS.43

The 1984 Centers for Disease Control (CDC) report

received widespread publicity and created, for want

of a better term, hysteria in many patients, whose

fear of blood transfusion was totally irrational.44 At

the same time, this hysteria has had two positive

effects: conservative blood transfusion practices

have been promoted, and donor screening has been

intensified. The screening, which was initiated to

exclude groups at high risk for HIV infection from

the donor population, has also served to exclude

one primary source of donors transmitting viral

hepatitis. Today, approximately 2% of AIDS cases

are attributed to the transfusion of single-donor

products, and 1% to clotting concentrates in patients with hemophilia.18,45 Most of these cases were

the result of blood transfusions prior to the advent

of serologic testing in March 1985, and it is believed

that this incidence will decrease in the future. Five

steps have been taken to decrease the risk of transfusion-associated AIDS:

1. High-risk groups such as intravenous drug

users, sexually active homosexual or bisexual males, individuals with symptoms

suggestive of AIDS, and sexual partners of

persons with or at risk for HIV infection

are excluded.

2. Donors’ confidential designation of their

blood “for laboratory use only” has been
Transfusion Therapy

333

added to the voluntary self-deferment to

avoid potential donor embarrassment or peer

pressure to donate.

3. All donor units are screened for HIV antibodies.

4. Blood products manufactured from pooled

donor plasma are heated or chemically

treated to inactivate HIV and other viruses

that might be present.

5. All cases of transfusion-associated AIDS

are completely investigated to identify

asymptomatic donors. When donors develop AIDS, recipients of all their prior donations should be investigated as part of the

American Red Cross’ Look-Back Program.46

The fact that transfusion recipients of AIDS are

infected involuntarily and unknowingly, in contrast to persons who have become infected through

risky behavior, has made transfusion-associated

AIDS an explosive public issue. Many recipients

first became aware of infection through the LookBack Program and, based in part on that program, it

is estimated that 12,000 blood transfusion recipients became infected prior to antibody testing in

1985.47 The current estimate of transfusion-associated AIDS is between 1:40,000 and 1:1,000,000.18

These cases are primarily attributed to blood donation during the 6- to 14-week window between

infection and the development of HIV antibodies.

Cytomegalovirus. Cytomegalovirus (CMV) is a

member of the herpes family, which are all DNA

viruses found intracellularly in leukocytes. Thus,

there is little risk of transfusion from acellular blood

components such as plasma or cryoprecipitate, and

minimal risk with leukocyte-poor RBCs. CMV infection is common, with 50% of donors having demonstrated prior exposure as manifested by antibodies, but only 5% to 12% of seropositive donors may

be infectious.48 Normally, only a mild febrile illness

is associated with viremia and viruria, followed by

seroconversion 13 to 16 weeks later. In contrast to

the mild infection described above, immunocompromised patients may develop serious, often fatal,

multisystem disease. Infants whose birth weight is

low (< 1,250 g), whose mothers are seronegative (ie,

no transplacental passive immunization), and who

receive seropositive blood are similarly at great risk.

Epstein-Barr Virus. Epstein-Barr virus may be

a potential cause of fever in patients without detectable CMV antibodies. More than 90% of donors

have antibodies to Epstein-Barr virus,49 and blood

is not screened for them because most individuals

are immune to this virus and not susceptible to

infection.

Bacterial Diseases

Bacterial contaminants do not present a problem

in transfusion practice because both the preservative and the storage temperature (4°C) are bacteriostatic for almost all species. Meticulous cleansing of

the puncture site and use of a closed-bag system for

collection will continue to make bacterial contaminants a rarity. The final step in preventing the

infusion of blood contaminated with bacteria is an

inspection of the unit prior to the administration.

Hemolyzed or cloudy units should be returned to

the blood bank for examination and culture.

Following RBC administration between April

1987 and May 1989, Yersinia enterocolitica produced

seven cases of sepsis, with five fatalities. These

deaths occurred in patients who had received units

of RBCs that had been stored for 26 to 40 days prior

to transfusion.50 The bacterium Y enterocolitica is

unique in that 4°C is not bacteriostatic. Whether

these cases are just the tip of the iceberg is uncertain

at this time, and the steps to be taken to prevent

additional occurrences are not clear. Obviously, a

return to 21-day shelf life would solve the problem.

However, the impact of that action on the available

blood supply would be likely to create more problems than it solves.

Syphilis is no longer common and Treponema

pallidum is unlikely to survive more than 72 hours in

citrated blood stored at 4°C. For that reason, the

American Association of Blood Banking standards

dropped the requirement for serologic testing for

syphilis in 1981. However, federal law, which takes

precedence over the American Association of Blood

Banking standards, still requires such testing. Because individuals with syphilis may engage in sexual

practices that make them at higher risk for HIV

infection, serologic testing may further protect the

blood supply from transfusion-transmitted hepatitis and AIDS.

For 20 years, it has been the practice to store

platelets at room temperature. Bacteremia following platelet transfusion was not recognized until

1981, when new plastic storage containers were

introduced; these improved gas exchange and permitted shelf life to be extended from 5 to 7 days.

Unfortunately, the longer shelf life also made possible the growth of any contaminating bacteria. As

a result of the potential for transfusion-related sepsis,

shelf life was returned to 5 days.51
Anesthesia and Perioperative Care of the Combat Casualty

334

Immunosuppression

In 1982, L. Burrows and P. Tartter52 suggested

that blood transfusion adversely affected survival

in colorectal cancer. A logical conclusion—that the

need for blood suggests a more advanced cancer—

has been refuted by other detailed studies.53,54 These

studies suggested that not only colorectal cancer

but also cancer of the lung, prostate, kidney, and

other organs were adversely affected by blood transfusion. This effect is seen more markedly following

transfusion of whole blood transfusion than of RBCs,

and has been attributed to an as-yet-unidentified

component of stored plasma (or associated cellulardamage debris).53 Currently, perioperative transfusions have now been correlated with early recurrence and poor prognosis in several forms of

malignancy, as well as with increased risk of bacterial infection.54 Patients receiving exchange transfusions as newborns, during cardiac surgery, or

with ulcerative colitis have all demonstrated alterations in their immune parameters; most startlingly,

these alterations may persist for 20 years.

There is a beneficial effect of blood transfusion

on immunosuppression: recipients of renal transplants who have received previous transfusions are

less likely to reject their donor kidneys.

Hemolytic Transfusion Reactions

Traditionally, hemolysis has been thought of as

occurring intravascularly or extravascularly. When

hemolysis is intravascular (ie, acute), it is associated with complement activation and release of free

hemoglobin into the plasma. Extravascular (ie,

chronic) hemolysis occurs when macrophages of

the reticuloendothelial system destroy RBCs outside the intravascular space; this is the normal

mechanism whereby senescent or otherwise nonviable erythrocytes are removed from circulation.

Hemolytic transfusion reaction occurs in both types

of hemolysis and in both awake and anesthetized

patients (Exhibit 14-4).42 Fever is the most common

symptom in both categories of patients; thus, a

hemolytic transfusion should be considered any

time a febrile reaction follows a transfusion. Similarly, hives and skin rash do not occur in patients

who are undergoing hemolytic reactions, which

distinguishes this serious reaction from the more

common, mild, allergic reactions. Many of these

early symptoms are not readily apparent in the

anesthetized patient. Indeed, blood oozing from

surgical or cannulation sites, hemoglobinuria, and

inappropriate hypotension are often the first signs

EXHIBIT 14-4

HEMOLYTIC TRANSFUSION REACTION

SYMPTOMATOLOGY

Acute Intravascular Hemolysis

Awake Patients

Fever

Tachycardia

Hemoglobinuria

Diffuse bleeding

Back pain

Nausea

Flushing

Dyspnea

Apprehension

Chest pain

Chills

Anesthetized Patients

Fever

Tachycardia

Hemoglobinuria

Diffuse bleeding

Hypotension

Chronic Extravascular Hemolysis and Delayed

Hemolytic Transfusion Reaction

Anemia

Mild jaundice

Reprinted with permission from Ellison N, Faust RJ.

Complications of blood transfusion. In: Saidman L,

Benumof J, eds. Anesthesia and Perioperative Complications. St. Louis, Mo: Mosby–Year Book; 1992: 511.

of a hemolytic transfusion reaction under anesthesia. Frequently, such patients are given additional

units of incompatible blood before medical personnel realize that a hemolytic transfusion reaction has

occurred.

Therapy for the hemolytic transfusion reaction is

aimed at preventing renal failure and DIC. Although mannitol has been the traditional drug of

choice, volume loading with crystalloid solution

and the intravenous administration of furosemide

to increase renal blood flow and urinary output are

now recommended. Of course, the transfusion must

be stopped as soon as the reaction is suspected.

Both that unit of blood and all others should be
Transfusion Therapy

335

rechecked in the blood bank, because a systematic

clerical error may have cleared all units that were

cross-matched at the same time. The coagulation

system must be monitored for the development of

DIC; platelet concentrates and FFP may be indicated if DIC develops.

Allergic Reactions

Signs and symptoms of an allergic reaction occur

in 1% to 2% of recipients and vary from localized

urticaria to (rarely) severe anaphylactic reaction.

The latter has an estimated incidence of 1 per 20,000

to 1 per 50,000 transfusions. Most allergic reactions

are thought to be caused by antibodies against

plasma proteins; most are mild and respond to

antihistamines.

Severe reactions, manifested by bronchospasm,

dyspnea, and pulmonary edema, require treatment

with epinephrine and steroids. These reactions may

be caused by immunoglobulin (Ig) G or antibodies

to IgA in an IgA-deficient patient. If IgA antibodies

are found in recipients’ serum, only extensively

washed RBCs and IgA-deficient plasma should subsequently be administered to that patient.

Febrile Reactions

Approximately 1% of all transfusions are accompanied by a temperature elevation with or without

chills. These reactions are usually caused by antibodies to leukocytes or platelets and occur in patients who have been sensitized previously. Leukocyte-poor components will prevent these reactions.

There is no definitive test with which to make the

diagnosis of a benign febrile reaction, which may

also be the first sign of a hemolytic reaction or the

infusion of a grossly contaminated unit of blood.

For this reason, temperature elevation requires that

more ominous causes be ruled out. When necessary, the fever can usually be treated with antipyretic

medication.

ALTERNATIVE SOLUTIONS FOR VOLUME REPLACEMENT

The establishment of an intravenous line is an

essential part of the management of almost every

patient to be anesthetized. Through that line, a

crystalloid solution is commonly administered.

There is no controversy over those two steps. The

controversy centers around whether to administer

crystalloid or colloid solutions to patients, especially those who are experiencing large fluid losses.

Table 14-4 compares extracellular fluid with the

various replacement fluids. Crystalloid solutions

freely cross capillary membranes, and within minutes, 60% to 80% of the solution is found in the

interstitial space, with only 20% to 40% remaining

intravascular. The failure of crystalloid solutions to

provide long-term intravascular expansion has led

some clinicians to advocate the use of colloid solutions.

Albumin, 5% or 25% in saline, has an intravascular half-life of 24 hours, as does plasma protein

fraction, which contains approximately 80% albuTABLE 14-4

COMPARISON OF EXTRACELLULAR FLUID AND VARIOUS REPLACEMENT SOLUTIONS

Na+ K+ Cl– Total Base Ca++ Mg+ Calories per

Solution (mEq/L) (mEq/L) (mEq/L) (mEq/L) pH (mEq/L) (mEq/L) Liter

Extracellular Fluid 138 5 108 27 7.4 5 3 12

5% Dextrose in Water 0 0 0 0 4.5 0 0 200

Normal Saline 154 0 154 0 6.0 0 0 0

Lactated Ringer’s 130 4 109 28 6.5 3 0 9

Normosol 140 5 98 50 7.4 0 3 24

5% Albumin 145 0 90 — 7.4 — — —

Heta starch 154 0 154 0 5.5 — — —

Reprinted with permission from Ellison N. Fluid and electrolytes and managing blood loss. In: Longnecker DE, Murphy FL, eds.

Introduction to Anesthesia: The Principles of Safe Practice. 8th ed. Philadelphia, Pa: WB Saunders; 1992: Chap 15: 171.
Anesthesia and Perioperative Care of the Combat Casualty

336

min and 20% globulin. The latter is less widely used

because of hypotension associated with rapid administration of large volumes.55 Two commercial

colloid preparations are available. Dextran is a

polymerized glucose molecule with a molecular

weight of 40,000 to 70,000 and an intravascular halflife of approximately 6 hours. Doses in excess of 1.5

g/kg/d may be associated with hemostatic disorders and will also interfere with blood typing and

cross-matching, owing to coating of the RBCs with

dextran. Hydroxyethyl starch is a synthetic polymer composed mainly of amylopectin and has a

intravascular half-life longer than 24 hours. The

maximum recommended dose is 20/mL/kg/d.

As previously mentioned, tolerance of blood loss

down to a predetermined target hemoglobin level is

a well-accepted and routine part of the fluid management of any patient undergoing elective surgery. In the patient who is bleeding massively,

ideal formulas frequently fail to work and blood

replacement is necessary. In these cases, autologous blood—other than that obtained by intraoperative scavenging—is rarely available. In terms of

volume administration, the need to provide adequate oxygen transport is really the only requirement for RBCs. As previously discussed, platelets

and procoagulate proteins may be necessary to secure hemostasis.

PRINCIPLES OF GOOD CIVILIAN TRANSFUSION PRACTICE

The maintenance of normovolemia is essential

for the preservation of homeostasis in the anesthetized patient. While the administration of blood or

blood products is often required to maintain

normovolemia, their administration may have lethal consequences, as the many complications cited

attest. Nevertheless, more than 12 million units of

blood or blood components are administered annually to more than 4 million patients in the United

States. Their administration is lifesaving in many

cases.

The three National Institutes of Health Consensus Development Conferences on Blood Product

Administration developed four common themes

that are especially applicable to civilian practice56:

1. Conservation is the most important way to

avoid the risks associated with transfusion

of blood products, and every effort should

be made to avoid or decrease the need to

administer allogenic blood products. Meticulous attention to hemostasis by surgeons and tolerance of lower hemoglobin

levels by anesthesiologists are examples of

appropriate conservative management.

2. There is a surprising, even appalling, lack

of adequate studies on the value of and

indications for the blood products in question. This lack is in contrast to the usual

well-controlled studies that have accompanied the introduction of other therapeutic maneuvers.

3. Educational efforts, directed at both patients and physicians, are essential. These

include, at the local level, strong proponents of modern transfusion practices to

disseminate available data and current recommendations.

4. Future research is required to answer basic

questions such as the role of platelets in

hemostasis, and clinical questions such as

the indications for administering RBCs,

platelets, and the coagulation factors in

plasma.

SUMMARY

former can be obviated by careful identification and

marriage of the patient’s blood sample and the

donor unit at the time a blood sample is collected,

during the cross-match, and again at the time the

donor unit is administered to the patient. Disease

transmission cannot always be avoided, for there is

always the possibility that the donor has recently

been infected and has not yet developed serologic

markers of infection. For this reason, it is essential

that patients receive only the minimum number of

units required to provide adequate oxygen-carrying capacity and to secure hemostasis.

In cases of massive blood loss, there is no substitute for the transfusion of allogenic blood. However, there are really only two indications for

transfusion: (1) to increase oxygen-carrying capacity, for which RBCs (ideally) and whole blood

(alternatively) are indicted; and (2) to secure

hemostasis, for which platelets and plasma are

indicated.

The administration of allogenic blood is not without risk. Among the several risks associated with

blood transfusion, hemolytic transfusion reaction

and disease transmission are the most feared. The
Transfusion Therapy

337

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2. Churchill ED. Surgeon to Soldiers. Philadelphia, Pa: JB Lippincott; 1972: 36–58.

3. Crosby WH, Akeroyd JH. Some immunohematologic results of large transfusions of group O blood and

recipients of other blood groups. Blood. 1954;9:103–116.

4. Miller RD. Complications of massive blood transfusions. Anesthesiology. 1973;39:82–93.

5. Collins JA. Problems associated with the massive transfusion of stored blood. Surgery. 1974;75:274–295.

6. Neel S. Medical Support of the US Army in Vietnam, 1965–1970. Washington, DC: Department of the Army; 1973:

114–126.

7. Barnes A, Allen TE. Transfusion subsequent to administration of universal-donor blood in Vietnam. JAMA.

1968;204:147–149.

8. Ellison N, Wurzel HA. The blood shortage: Is other transfusion an answer? Anesthesiology. 1975;43:288–290.

9. Myhre BA, Bove JR, Schmidt PJ. Wrong blood—a needless cause of surgical deaths. Anesth Analg. 1981;60:

777–778.

10. Ellison N. Central venous access, a mixed blessing. Semin Anesth. 1990;9:288–297.

11. Courington FW. Anesthesia guidelines for the trauma patient. Semin Anesth. 1985;4:92–101.

12. Schmidt PJ. Red cells for transfusion. N Engl J Med. 1978;299:1411–1412.

13. Schmidt PJ. Component therapy. Int Anesthesiol Clin. 1982;20:23–43.

14. Counts RB, Haisch C, Simon TL. Hemostasis in massively transfused patients. Ann Surg. 1979;190:91–99.

15. Stehling LC, Zauder HL. How low can we go? Is there a way to know? Transfusion. 1990;30:1–3.

16. Stehling LC, Zauder HL. Acute normovolemic hemodilution. Transfusion. 1991;31:857–868.

17. Ballinger CA, Collins JA. Experts opine. Surg Anesth. 1975;19:301–302.

18. Consensus Development Conference. Perioperative red blood cell transfusion. JAMA. 1988;260:2700–2703.

19. Levine E, Rosen A, Schgal L, et al. Physiologic effects of acute anemia implications for reduced transfusion

trigger. Transfusion. 1990;30:11–14.

20. Boerema I, Meyre NG, Brummelkamp WK, et al. Life without blood. J Cardiovasc Surg. 1960;1:133–146.

21. Hondow JA, Russell WJ, Duncan BM, et al. The stability of coagulation factors in stored blood. Aust N Z J Surg.

1982;52:265–269.

22. Murray DJ, Olson J, Strauss R, Tinker JH. Coagulation changes during packed red cell replacement of major

blood loss. Anesthesiology. 1988;69:839–845.

23. Pisciott PT, ed. Blood Transfusion Therapy: A Physician Handbook. 3rd ed. Arlington, Va: American Association of

Blood Banks; 1989.
Anesthesia and Perioperative Care of the Combat Casualty

338

24. Ellison N. Hemostasis in the trauma patient. Semin Anesth. 1985;4:163–176.

25. Ciavarella D, Reed RL, Counts RB, et al. Clotting factor levels and the risk of diffuse microvascular bleeding in

the massively transfused patient. Br J Haematol. 1987;67:365–368.

26. Consensus Development Conference. Fresh-frozen plasma: Indications and risks. JAMA. 1985;253:551–553.

27. Braunstein AH, Oberman HA. Transfusion of plasma components. Transfusion. 1984;24:281–285.

28. Collins JA, Simmons RL, James PM, et al. Acid–base status of seriously wounded casualties, II: Resuscitation

with stored blood. Ann Surg. 1971;173:6–10.

29. Miller RD, Tong MJ, Robbins TO. Effects of massive transfusion of blood on acid–base balance. JAMA.

1971;216:1762–1765.

30. Zauder HL. Massive transfusion. Int Anesthesiol Clin. 1982;20:157–170.

31. Jameson LC, Popic PM, Harris BA. Hyperkalemic death during use of high-capacity fluid warmer for massive

transfusion. Anesthesiology. 1990;73:1050–1052.

32. Bunker JP, Stetson JB, Coe RC, et al. Citric acid intoxication. JAMA. 1955;157:1361–1363.

33. Denlinger JK, Nahrwold ML, Gibbs DS, Lecky JH. Hypocalcemia during rapid blood transfusion in anesthetized

man. Br J Anaesth. 1976;78:995–1000.

34. Beeson BB. Jaundice occurring one to four months after transfusion of blood or plasma: Report of seven cases.

JAMA. 1943;121:1332–1333.

35. Sazama K: Report of three hundred fifty-five transfusion-associated deaths: 1976–1985. Transfusion. 1990;30:583–590.

36. Walsh JH, Purcell RH, Morrow AG. Post-transfusion hepatitis after open heart operations. JAMA. 1965;211:261–265.

37. Alter HJ, Holland PV, Purcell RH, et al. Post-transfusion hepatitis after exclusion of commercial and hepatitisB antigen donors. Ann Intern Med. 1972;77:691–699.

38. Krugman S, Giles JP, Hammond J. Infectious hepatitis: Evidence for two distinctive clinical, epidemiological,

and immunological types of infections. JAMA. 1967;200:365–367.

39. Blumberg BS, Gerstley BJS, Hungerford DA, London T, Sutnick AI. A serum antigen (Australia antigen) in

Down’s syndrome, leukemia, and hepatitis. Ann Intern Med. 1967;66:924–931.

40. Rutherford CJ. Transfusion-associated disease. In: Churchill WH, Kurtz SR, eds. Transfusion Medicine. Cambridge, Mass: Blackwell Scientific Publications; 1988: 107–127.

41. Kuo G, Choo O-L, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of non-A, nonB hepatitis. Science. 1989;244:362–364.

42. Ellison N, Faust RJ. Complications of blood transfusion. In: Saidman L, Benumof J, eds. Anesthesia and

Perioperative Complications. St. Louis, Mo: Mosby–Year Book; 1992: Chap 21.

43. Ammann AJ, Cowan MJ, Wara DW, et al. Acquired immune deficiency in an infant: Possible transmission by

means of blood products. Lancet. 1983;1:956–958.

44. Curran JW, Lawrence DN, Jaffe H, et al. Acquired immune deficiency syndrome (AIDS) associated with

transfusions. N Engl J Med. 1984;310:69–75.
Transfusion Therapy

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45. Busch MP, Young MJ, Samson SM, et al. Risk of human immunodeficiency virus (HIV) transmission by blood

transfusions before the implementation of HIV-1 antibody screening. Transfusion. 1991;31:4–11.

46. Busch MP. Let’s look at human immunodeficiency virus look-back before leaping into hepatitis C virus lookback. Transfusion. 1991;31:655–661.

47. Peterman TA, Lui K-J, Lawrence DN, Allan JR. Estimating the risks of transfusion-associated acquired immune

deficiency syndrome in humans. Transfusion. 1987;27:371–374.

48. Prince AM, Szmuness W, Millian SJ, David D. A serologic study of cytomegalic virus infections associated with

blood transfusion. N Engl J Med. 1971;284:1125–1131.

49. Henle W, Henle G. Epstein-Barr virus and blood transfusions. Prog Clin Biol Res. 1985;182:201–209.

50. Tipple MA, Bland LA, Murphy JJ, et al. Sepsis associated with transfusion of red cells contaminated with Yersinia

enterocolitica. Transfusion. 1990;26:209–213.

51. Food and Drug Administration. Reduction of the maximum platelet storage period to five days in an approved

container. FDA Bulletin. Washington, DC: Food and Drug Administration; June 2, 1986.

52. Burrows L, Tartter P. Effect of blood transfusions on colonic malignancy recurrence rate. Lancet. 1982;2:662.

53. Blumberg N, Heal JM. Transfusion and recipient immune function. Arch Pathol Lab Med. 1989;113:246–253.

54. Schriemer PA, Longnecker DE, Mintz PD. The possible immunosuppressive effects of perioperative blood

transfusion in cancer patients. Anesthesiology. 1988;68:422–428.

55. Ellison N, Behar M, MacVaugh H III, Marshall BE. Bradycardia, plasma protein fraction, and hypotension. Ann

Thorac Surg. 1980;29:15–19.

56. Ellison N. A commentary on three NIH Consensus Development Conferences on transfusion medicine. Anesth

Clin NA. 1990;8:609–624.
Military Transfusion Practice

341

CHARLES D. BOLAN, JR., M.D.*; AND NOEL R. WEBSTER, M.S.†

INTRODUCTION

BLOOD TRANSFUSION AT THE SECOND ECHELON

Transfusion Experience From Previous Wars

Field Administration of Group O Packed Red Blood Cells

Technical Factors

Clinical Factors

Field Management of Transfusion Reactions

TRANSFUSION SUPPORT AT THE THIRD AND FOURTH ECHELONS

Logistical Aspects

Effect of Massive Transfusion

Emergency Collection and Transfusion of Whole Blood Donated in the Field

MILITARILY UNIQUE CONSIDERATIONS

Group-Specific Transfusion and Random-Mix Blood

Identification Tags

Female Casualties and Rh Blood Groups

Active Research Efforts

PLANNING AND TRAINING

Adjustments From Civilian Medicine

Hands-On Practice: Lessons Learned, Lost, and Learned Again

A Second-Echelon Transfusion Strategy

Planning at the Third and Fourth Echelons

SUMMARY

GUIDELINES FOR INTERACTING WITH THE BLOOD-DISTRIBUTION SYSTEM

*Major, Medical Corps, U.S. Army; Assistant Chief of Medicine, Walter Reed Army Medical Center, Washington, D. C. 20307-5001

†Lieutenant Colonel, Medical Service, U.S. Army; Deputy Director, Armed Services Blood Program Office, Falls Church, Virginia 22041

Chapter 15

MILITARY TRANSFUSION PRACTICE
Anesthesia and Perioperative Care of the Combat Casualty

342

INTRODUCTION

Transfusion support of resuscitation and surgery

in the combat zone is a cornerstone of military

medicine.1–8 Military doctrine includes planning

for blood products and the provision of blood components in the combat zone, but it does not include

implementation of patient care. This chapter describes a safe and effective transfusion service for

the combat zone. It covers clinical, technical, and

military aspects of planning and training, including

blood component therapy, the variety of transfusion practices in the four echelons of care, the special requirements for women, and the possible impact of research on military blood programs.

Military doctrine for health service support and

blood management in a theater of operations is

outlined in manuals such as U.S. Army Field Manual 8-55, Planning for Health Service Support (FM 8-

55).9 The principles for transfusion practice by

echelon are shown in Table 15-1. Doctrine for

availability of blood components in theater and for

planning factors for blood products is shown in

Tables 15-2 and 15-3, respectively. The material

in this chapter outlines the implementation of

doctrine.

The definition of echelons of care varies according to military service and mission; it is best viewed

as a continuum of care rather than as care delivered

within rigid, fixed boundaries.10 In general, second-echelon units (constituted by the medical company/battalion and its organic units) support battalion aid stations, casualty collection points, and

other first-echelon of care units. In the army and

marines, “second-echelon” corresponds to “division-level” units (eg, clearing stations) that support

the medical platoons of maneuver battalions, and

the terms are sometimes used interchangeably. Second-echelon units, which are authorized to transfuse only universal-donor (ie, blood group O packed

TABLE 15-1

BLOOD TRANSFUSION PRACTICES BY ECHELON

First none — — — —

Second PRBCs O, Rh +/– ABO group donor RBCs† 50 units RBC per Third-echelon BSU

field medical

refrigerator

Third

D304* PRBCs O, A, B, Rh +/– ABO and Rh-group 480 units liquid RBCs Third-echelon BSU

patient and donor RBCs†

Major side, immediate

spin cross-match

D404* PRBCs O, A, B, Rh +/– Same as D404 Same as D304, Third-echelon BSU

plus 475 units frozen

FFP A, B, AB, Rh +/– None 20 units Third-echelon BSU

PLT O, A, Rh +/– None 5 units‡ Third-echelon BSU or MTF

Fourth Same as D404 Same as D404 Same as D404 Same as D404 Fourth-echelon BSU

*Capability to collect and perform the ABO and Rh group determination on 180 units of whole blood for extreme emergencies. D304

is liquid-only DEPMEDS module. D404 is hybrid liquid-frozen DEPMEDS module. D405 is a frozen-blood augmentation set that

converts the D304 to D404 capability.

†Not necessary if Armed Services Whole Blood Processing Laboratory has verified the ABO group.

‡One unit = one 6-pack

BSU: blood supply unit; DEPMEDS: Deployable Medical Systems; FFP: fresh frozen plasma; MMS: medical material set; MTF:

medical treatment facility; PLT: platelet concentrate; PRBCs: packed red blood cells

Adapted from US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA; approved final

draft January 1994. Field Manual 8–55: 8-6–8-7.

Echelon/ Blood ABO and Transfusion Service Storage Blood

MMS Product Rh Group Procedures Capacity Resupply
Military Transfusion Practice

343

TABLE 15-2

BLOOD PRODUCTS AVAILABLE TO THE THEATER

Blood Group

Unit of Shelf Life for Echelon Availability

Product Issue Storage Transfusion Availability O +/– A +/– B +/– AB +/–

Liquid PRBCs ~ 250 mL 35 d 35 d Second & third (MASH) 100% — — —

Third (CSH) & fourth 50% 40% 10% —

Frozen/deglycerolized RBCs ~ 250 mL 10 y 3 d (postwash) Third & fourth 100% — — —

FFP ~ 250 mL 1 y 24 h (postthaw) Third & fourth — 50% 25% 25%

Platelet

concentrate ~ 60 mL 5 d 5 d Third & fourth 50% 50% —* —*

*Will be provided by blood bank platoon and medical treatment facilities by in-theater blood collections

CSH: combat support hospital; FFP: fresh frozen plasma; MASH: mobile army surgical hospital; PRBCs: packed red blood cells;

RBCs: red blood cells

Adapted from US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA; approved final

draft January 1994. Field Manual 8-55: 8-6.

TABLE 15-3

BLOOD PLANNING FACTORS

Blood Component Planning Factor

Red blood cells 4 units for each WIA and each NBI casualty initially admitted to a hospital*

Fresh frozen plasma 0.08 units for each hospitalized WIA or NBI casualty

Platelet concentrate 0.04 units for each hospitalized WIA or NBI casualty

*For blood-planning purposes, only count the WIA or NBI once in the system, not each time the patient is seen or admitted

NBI: nonbattle injury; WIA: wounded in action

Reprinted from US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA; approved final

draft January 1994. Field Manual 8-55: 8-11.

cells, but not platelets or fresh frozen plasma (FFP).

Platelets and FFP are available at CSHs as well as at

the fourth echelon. MASHs, CSHs, and fourthechelon facilities are all authorized for emergency

collection of limited units of whole blood. Fourthechelon facilities, such as field hospitals (FH) and

general hospitals (GH), have blood banking support similar to that found in a civilian medical

center.

Military transfusion therapy is directed to best

meet the clinical needs of the casualty within the

operational constraints of the tactical situation. The

current concept of medical support within a theater

of operations is being revised, and units such as

MASH, CSH, GH and FH are being reconfigured.

red blood cells ([PRBCs]), have limited patientholding, laboratory, and radiological capabilities.

Located forward of hospitals and lacking surgical

capability unless augmented by a forward surgical

team, second-echelon units are strategically situated for triage, resuscitation, and stabilization of

casualties before they are medically evacuated to

higher echelons of care.

Third-echelon facilities (mobile army surgical

hospitals [MASHs] and combat support hospitals

[CSHs]) provide resuscitative and definitive surgery and have much more extensive laboratory,

radiological, patient holding, and nursing support

than second-echelon units. As presently configured, the MASH provides liquid group O red blood
Anesthesia and Perioperative Care of the Combat Casualty

344

For purposes of this chapter, second-echelon transfusion capability refers to the use of group O PRBCs to

support resuscitation, and third-echelon transfusion

capability refers to support of resuscitative surgery

without benefit of a full, tertiary care, blood banking capability. In practice, these arbitrary guidelines blur. Resuscitation with blood remains an

integral component of surgery at any echelon, and

forward surgical treatment squads may be assigned

to augment a division clearing station. Conversely,

a medical clearing company may augment a CSH, a

MASH, or a GH to provide resuscitation and second-echelon medical support in the corps support

zone or the communication zone.

BLOOD TRANSFUSION AT THE SECOND ECHELON

Second-echelon medical units are authorized liquid group O PRBCs for initial resuscitation and

stabilization. These units thus bring blood the farthest forward on the battlefield and the closest to

the casualties. This approach is not new. During

World War II, the need for whole blood was recognized and was at least occasionally available at

clearing stations (Figure 15-1). The ideal, of course,

is to provide blood as close as possible to the location where the casualty was injured, but logistical

considerations make this difficult.

Second-echelon blood transfusion conforms with

two principles taught in the American College of

Surgeons’ Advanced Trauma Life Support (ATLS)

course11:

1. Resuscitation begins as soon as possible

(ie, the civilian “Golden Hour”, but in military medicine this critical time is much

shorter; see Chapter 1, Combat Trauma

Overview).

2. Resuscitation with blood is given for hemorrhage of more than 25% to 30% of a

casualty’s blood volume (Figure 15-2).

Casualties with this degree of hemorrhage

need the restoration of oxygen-carrying

capability that only red blood cells provide; volume expansion with plasma, crystalloid solutions, or albumin will not be

sufficient to treat hypovolemic shock.

Transfusion Experience From Previous Wars

The transfusion of red blood cells, either for

stabilization prior to medical evacuation or

perioperatively, is an essential element of military

medical therapy in forward locations. The experiences that follow, of U.S. Army medical officers

during World War II, the Korean War, the Vietnam

War, and the Persian Gulf War, all (a) describe the

use of blood at the second echelon and (b) further

the rationale for the use of blood in forward areas.

Fig. 15-1. Whole blood is being administered on 21 April

1945 to a casualty at a clearing station of the 102nd

Medical Battalion during the savage Okinawa Campaign.

Historically, the emphasis has been on giving blood at

the surgical level; this photograph reminds us that blood

can be given far forward, near the point where casualties

are injured. In fact, during the D-day invasion in June

1944, U.S. Navy assault surgeons who landed with U.S.

Army troops on Normandy beachheads each carried

units of whole blood packed in ice, intending to administer it at the first echelon. Sources: (1) Ben Eiseman, MD,

Rear Admiral, Medical Corps, US Navy Reserve (ret),

Denver, Colo. Personal communication, June 1995. (2)

Photograph: Reprinted from Flick JB, Raine F, Robertson

RC. Pacific Ocean areas. In: Carter NB, ed. Activities of

Surgical Consultants. Vol 2. In: Coates JB Jr, ed. Surgery in

World War II. Washington, DC: US Army Medical Department, Office of The Surgeon General; 1964: 680.
Military Transfusion Practice

345

received 1 or more pints of bank blood at a clearing

company. Some casualties received as much as 6

pints in an hour.12(p634)

. . . .

Colonel Churchill had himself supervised the development of the program from his arrival in North

Africa in March 1943. His first recommendations

were the result of his personal verification of the

need for whole blood by his own examination of

wounded casualties in clearing stations and forward hospitals.12(p443)

Korea

Our military surgeons have become increasingly

bold in the use of blood for resuscitation of

casualties.3(p439)

. . . .

[T]he use of universal blood in the combat zone is

a valuable military expedient.... Small but effective

banks of blood can be established at the forward

aid stations.3(p455)

. . . .

World War II

[T]ransfusions...were not ordinarily given in battalion aid stations or in collecting and clearing

stations, though occasionally as during the rapid

advance at Anzio, these installations were so far

ahead of field hospitals that blood was sent to

them.12(p406)

. . . .

[I]f hemorrhage had occurred, only whole blood

could meet the situation. Blood had been used

extensively as far forward as battalion aid stations.

Given over a 24-hour period, 5,000 cc. could completely change the appearance and outlook of a

critically wounded casualty.12(p635)

. . . .

When whole blood was immediately available as

far forward as clearing companies and portable

surgical hospitals, it became the practice to use

plasma only when blood was not at hand.

By March of 1945, it was routine for invasion forces

to carry blood ashore with them, and it was not

uncommon, on reading a casualty’s Emergency

Medical Tag in a rear hospital, to find that he had

Fig. 15-2. The flasks that this man and woman hold contain fluid representing approximately 25% of their blood

volume, based on their gender and weight. Casualties who lose more than this amount of blood require transfusion

support with red blood cells to prevent shock.
Anesthesia and Perioperative Care of the Combat Casualty

346

In Korea—a stable situation—we sent group O blood

forward to the aid stations, where it was stored in

wet ice boxes.13

Vietnam

As the troop strength built up, so did the number of

medical units receiving blood, ranging from frontline clearing companies to 400-bed evacuation

hospitals. By February of 1966 there were 26 separate

medical units receiving blood, including 15 medical

clearing companies, 3 surgical hospitals etc....5(p1478)

. . . .

During the Plei Me battle, one clearing company of

the 1st Air Cavalry Division handled most of the

patients, giving 154 units to 94 patients, including

15 units to one soldier with wounds of the arm and

throat.5(p1479)

Persian Gulf War

[T]he entire concept and technical details of [administering] blood at the division clearing station

have largely been ignored.... [S]ince most patients

in the Vietnam war overflew clearing stations and

went directly to corps-level hospitals, the institutional memory and clinical art of division blood

management suffered a nearly 40-year lapse.14

Case Presentation

During Operation Desert Shield of the Persian Gulf

War, a 7-year-old boy stepped on a land mine near Al

Nasiryah, Iraq, and suffered a near total amputation of his

left leg. He was taken by his father to the aid station of 1st

Battalion, 504th Parachute Infantry Regiment, 82nd Airborne Division, where bleeding was controlled and intravenous crystalloid solution administered. Despite this

initial resuscitation, the child remained in shock. Air evacuation was not available, and he was transported as an

emergency via ground ambulance to the medical clearing

station in direct support of the brigade.

On arrival at the medical clearing station, the patient

remained pale and lethargic. The pulse was more than

150 beats per minute and barely palpable at the femoral

artery. The skin was cool and clammy. There was no

bleeding from the wound, which was properly bandaged

and splinted; two intravenous lines were open, and normal saline was being administered.

One unit of group O PRBCs was administered. The

patient’s mental status improved and his pink color returned. The pulse became stronger and slowed toward

the normal range. A second unit of group O blood was

administered and the patient transferred to a holding tent

to await routine evacuation.

The management of this casualty illustrates

the important role played by maintaining a blood

transfusion capability in a second-echelon facility.

Clinically, the child was in severe hemorrhagic

shock and responded only to replacement of lost

blood volume with circulating red blood cells.

Large-volume resuscitation with normal saline

failed to reverse shock. Plasma, albumin, or other

colloid may raise blood pressure and provide temporary improvement, but fail to control shock without red blood cell replacement.6,11 Logistically, after

resuscitation with blood and stabilization, the patient required only routine evacuation, thus reducing the burden on aeromedical evacuation when it

resumed.

Field Administration of Group O Packed Red

Blood Cells

Basic technical details such as supply and storage

requirements; inspection, record-keeping, and inventory procedures; and clinical principles such as

technique and patient evaluation must be considered when group O PRBCs are to be administered in

the field (Exhibit 15-1 and Figure 15-3). The critical

importance of training is discussed later in this

chapter.

Technical Factors

Technical factors involve maintaining appropriate transfusion supplies as well as the storage and

record keeping required to maintain 30 to 60 units

of blood available for transfusion. Infusion sets,

normal saline, and group O blood stored in a small

thermostabilizer constitute all the supplies necessary to maintain a second-echelon transfusion capability (Figure 15-4). Units of PRBCs can also be

safely stored in rigid polystyrene plastic chests containing wet ice. Since all supplies can be stored in

the equivalent space of two small chests, a secondechelon transfusion program is entirely consistent

with the mobility of a light infantry or airborne unit.

The transfusion log is essential; in it, records are

kept of unit numbers, blood types, inspections, temperatures, expiration dates, and information about

the recipient (Figure 15-5). However, log books are

not available for field use—especially at the second

echelon—and must be adapted by hand from standard-issue notebooks.

The temperature of the blood must be maintained between 1°C and 6°C—this must be ensured

with daily inspections of blood stored in refriger-
Military Transfusion Practice

347

EXHIBIT 15-1

FIELD ADMINISTRATION OF GROUP O PACKED RED BLOOD CELLS

Technical Factors

• Required Supplies. Infusion sets (eg, from the Blood Chest Packing List of the 307th Medical Battalion

[Airborne] Sets, Kits, and Outfits Components Listing, the Chest Med Inst & Supply No. 5, National

Stock Number [NSN] 6545-00-914-3500, and Blood Recipient Set Y-Type, NSN 6515-01-128-1407),

normal saline, blood log books, blood refrigerator, and group O packed red blood cells (PRBCs) are

required.

• Storage. Maintain temperature between 1°C and 6°C. Shelf life is 35 days after collection for citrate

phosphate dextrose adenine (CPDA-1) PRBCs. Blood will be safe if it remains with wet ice. Consider

putting blood in plastic bags to protect label legibility.

• Inspection. Inspect daily for temperature and for evidence of hemolysis, package breakdown, or

infection.

• Records. For all units, record dates, unit numbers, ABO group and Rh type, expiration date, and results

of daily inspection. When a unit is infused, record unit information as above, along with the date of

transfusion and the casualty’s name, service number, and military unit.

• Inventory. Maintain 30 to 60 units for a clearing station, 500 or more units at higher echelons. Coordinate closely with the blood supplier. Determine how quickly inventory can be reconstituted.

• Reports. Report information on inventory, numbers of blood groups, and expiration dates of units on

hand. Figure 15-3 is sample blood report.

Clinical Factors

• Technique. Infuse intravenously using an infusion set and normal saline.

° When group O PRBCs are used, it is not necessary to check the casualty’s ABO blood group.

° If the casualty is a woman, make sure Rh factor is correctly matched. Transfuse with Rh-negative

blood if Rh factor is unknown.

• Annotation. Record the transfusion in the transfusion log and on the casualty’s field aid card. Consider

pinning the empty unit package to the casualty’s clothing for transfer with the casualty to the next

echelon of care.

• Transfusion Volume. Follow clinical, not laboratory, criteria for response. Look for return of pink color and

blood pressure higher than 80 mm Hg systolic. Do not use field laboratory tests to guide transfusion.

Consider whether the casualty is likely to be bleeding internally. Avoid excessive transfusion both to

conserve blood and to possibly reduce blood loss.

ated or thermostabilized containers, or by keeping

blood stored with wet ice. If placed with wet ice, the

units may be first placed in a plastic bag to protect

against water damage. The expiration date for

PRBCs collected in citrate-phosphate-dextrose-adenine (CPDA-1) solution shall not exceed 35 days

after phlebotomy. Units must be inspected daily for

evidence of hemolysis and package integrity. It is

crucial that the number, type, and expiration dates

of all units be recorded in the daily log. The

recipient’s patient identification number, name,

military unit, and the date should also be recorded

when a unit is transfused. It is imperative that each

unit received have a final record of disposition (eg,

the unit was transfused, destroyed, shipped to another facility, etc) and that the record be maintained

indefinitely. In prior conflicts, some physicians

have stored blood for up to 10 days past expiration

when daily inspections remained normal for use as

a last resort in a mass casualty situation. Personnel

must quickly determine the frequency and format

of desired reports and procedures for resupply with

the blood-supply program (these are discussed later

in this chapter under Planning and Training).

Clinical Factors

Since the major cause of transfusion reactions is

the inadvertent administration of correctly typed

and cross-matched blood to the wrong patient, it is
Anesthesia and Perioperative Care of the Combat Casualty

348

This is Blood Report Over

Line 14 (or time) (Message hour-minute-zone when required. Use Zulu Time!)

Line 15 (or authentication is) (Message authentication IAW JTF procedures.)

Line 7 (or status of) (Name or designator code of the unit of activity reporting status of blood

supplies if other than message originator.)

Line 8 (or activity) (Reporting unit’s activity brevity code letter if other than message

originator.)

Line 9 (or on hand) (Number and code of each blood product on hand.)

Line 10 (or needed) (Number and code of each blood product requested.)

Line 11 (or expiration) (Estimate of total number of blood products by group and of those that

will expire in the next 7 days.)

Line 12 (or resupply) (Estimate of total number of blood products by group and type required

for resupply in the next 7 days.)

Line 13 (or narrative)

Line 4 (or location) (Unit location in LAT/LONG, UTM, or place name.)

Line 5 (or rendezvous) (NAVAL VESSELS ONLY: Projected location in LAT/LONG or place

name for delivery of blood products.)

Line 6 (or arrival) (NAVAL VESSELS ONLY: Estimated time of arrival [day, time, time

zone, month, year] at the projected location.)

(Addressee) (Originator)

Addressee answers, then originator responds: This is

FLASH IMMEDIATE PRIORITY ROUTINE (Underline and transmit the precedence of this message.)

TOP SECRET SECRET CONFIDENTIAL UNCLASSIFIED (Underline and transmit the security classification of this message.)

BLOOD REPORT

Line 1 (or as of) (Day-time-zone of this report. Use Zulu time!)

Line 2 (or unit) (Reporting unit’s name or designator code.)

Line 3 (or activity) (Reporting unit’s activity brevity code letter.)

Lines 7–12 may be repeated as a group when more than one activity must be reported in a message.

MESSAGE MODIFIERS

Management Offices: A Joint Blood Program Office

B Area Joint Blood Program Office

Facilities: C Armed Services Whole Blood Processing Laboratory

D Blood Donor Center

E Blood Products Depot

F Blood Transshipment Center

G Blood Supply Unit

H Medical Treatment Facility

I Naval Vessel

Blood Products: J Red Blood Cells (Packed)

K Whole Blood

L Frozen Red Blood Cells

M Fresh Frozen Plasma

N Frozen Platelets

Blood Groups: O To Be Determined

P To Be Determined

Q Random Group and Types O, A, B

R Random Group and Types O, A

S Group O

T Group A

U Group B

V Group AB

Time Frame: W Required Within 12 Hours

X Required Within 24 Hours

Y Required Within 48 Hours

Miscellaneous: Z Not Applicable, or See Remarks

Fig. 15-3. Sample Blood Report used by the 655th Medical Company (–), USAREUR Blood Bank, Operation Desert

Shield, Fall, 1990.
Military Transfusion Practice

349

a c

resuscitation is not yet known with certainty.18

Laboratory tests such as measuring the hematocrit

are not appropriate measures of response to transfusion in trauma patients in a field setting.

After transfusion, the unit’s number and blood

type should be noted on the casualty’s field aid card

(ie, the emergency medical tag); the empty unit

should be pinned to the patient’s clothing while the

patient is being transported. Knowledge of the

number and type of previously transfused units

may be useful in guiding therapy for possible subsequent transfusions at higher echelons.

Field Management of Transfusion Reactions

The signs and symptoms of a transfusion reaction can be subtle.19 The diagnosis may be especially difficult in a field setting and in casualties

with internal injuries and dirty wounds. However,

abrupt fever, chills, hypotension, hemoglobinuria,

hemoglobinemia (in plasma), or shortness of breath

in the appropriate setting may provide sufficient

evidence of hemolysis to initiate therapy (Exhibit

15-2). Infusion of the unit of blood should be stopped

while the intravenous catheter remains in place

infusing normal saline. Every attempt should be

made to maintain blood pressure and urinary outimperative to use only group O PRBCs obtained

through established blood program channels at second-echelon facilities. The appropriate connections

between patient, infusion set, and donor unit should

be mastered and practiced in advance in mock situations with simulated patients before being used on

casualties.

Normal saline is the only crystalloid fluid to be

infused with blood during a transfusion. Hypotonic solutions such as dextrose in water or halfnormal saline can cause hemolysis. Calcium in

lactated Ringer’s solution will complex citrate and

may cause coagulation.15 The American Association of Blood Banks’ Technical Manual recommends

that lactated Ringer’s solution not be infused with

blood.16

The volume of blood required for transfusion is

determined clinically and should be an amount that

restores mentation, circulatory stability, pink color,

and a systolic blood pressure of about 80 mm Hg to

the patient. Continued infusion after these criteria

have been met can promote further bleeding in

patients with internal injuries, and waste limited

supplies of blood.2 Recent studies suggest that

immediate, full-volume resuscitation may not be

optimal for patients with penetrating chest injuries,17 and the proper timing and amount of fluid

Fig. 15-4. Blood supplies and refrigerator (thermostabilizer, also called the blood box) for field transfusion of packed

red blood cells (PRBCs). (a) Infusion set needed to administer blood, which should be infused with normal saline

through a simple intravenous catheter. (b) Normal saline; blood should not be transfused through the same catheter

with hypotonic fluid or lactated Ringer’s solution. (c) The thermostabilizer is manufactured by Thermopol, Inc,

Chicago, Ill; weight: 83 lb; dimensions: 25 in. (w) x 21 in. (l) x 22.5 in. (h). This chest can be connected to either generator

power or the direct current of a vehicle battery. These items, the transfusion log book and reports seen in Figure 15-

5, and group O PRBCs constitute all the supplies required to run an effective second-echelon transfusion program.

b
Anesthesia and Perioperative Care of the Combat Casualty

350 Blood Inventory Tracking Operation

Name of Medical Care Facility

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Expiration Cryovial Disposition Report to

Unit Number Date Product Type Location BSU Medical Unit Date Issued Date Reason Method Location JBPO

1. Input number of unit of blood 7. Date blood was issued by the BSU, or received by the medical facility

2. Input the expiration date of unit of blood 8. Date blood was disposed or shipped

3. Input ABO/Rh of unit 9. Indicate the reason that the blood was dispositioned (ie, expired, shipped)

4. If frozen units are deglycerolized, indicate the location of the cryovial if known 10. Means of disposal (ie, incinerated, autoclaved)

5. Indicate the name of the BSU that supplied the unit of blood 11. Where the blood was dispositioned (ie, afloat)

6. Medical care facility dispositioning the blood 12. JBPO will indicate date when report is received

Frequency of transmission of reports will be determined by the JBPO.

At the least, the disposition of units must be submitted on redeployment of the MTF.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Expiration Cryovial Date Patient’s Report to

Unit Number Date Product Type Location BSU Medical Unit Transfused Name Patient’s SSN Note JBPO

1. Input number of blood unit transfused 7. Date of blood transfusion

2. Input the expiration date of the blood unit transfused 8. If unknown, indicate nationality or branch or service (ie, Haitian 1)

3. Input ABO/Rh of unit transfused 9. If unknown, indicate patient’s nationality (ie, Haitian)

4. If deglycerolized red cells are transfused, indicate thelocation of the cryovial if known 10. Indicate the reason for the transfusion (ie, gunshot wound)

5. Input name of BSU supplying blood; if unknown, leave blank 11. JBPO will indicate date when report is received

6. Medical care facility transfusing the blood

Frequency of submission of reports will be determined by the JBPO.

At the least, the disposition of transfused units must be submitted on redeployment of the MTF.

Fig. 15-5. Blood Inventory tracking operation reports. Blood log is a standard-issue notebook adapted for use with hand-drawn labels and report sheets. Blood

Inventory Tracking Operation reports adapted from US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA;

approved final draft January 1994. Field Manual 8-55: Chap 8, Section V.

Blood Inventory Tracking Operation

Transfused Units
Military Transfusion Practice

351

EXHIBIT 15-2

FIELD MANAGEMENT OF A TRANSFUSION REACTION

• Stop the infusion of blood. Continue to infuse normal saline through the intravenous line.

• Examine the urine for hemoglobinuria. Examine plasma for hemoglobinemia.

• Maintain blood pressure and urinary output with saline. Consider administering mannitol or furosemide

after volume repletion if the patient is oliguric.

• Reexamine the donor unit for seal integrity, evidence of hemolysis or infection, and recheck the transfusion log for clerical error.

• Annotate the field medical card with a description of the suspected reaction and the therapy provided.

Transfer the unit suspected of causing the reaction to the next echelon of care with the casualty.

TABLE 15-4

MEDICAL LABORATORY PROCEDURES,

BLOOD BANK

Description MASH CSH FH GH

Perform blood group x x xx

and type (ABO, Rh)

Perform blood cross-matches x xx

Thaw fresh frozen plasma x xx

Issue platelet concentrate x xx

Reprinted from US Department of the Army. Planning for Health

Service Support. Washington, DC: Headquarters, DA; approved

final draft January 1994. Field Manual 8–55: 7-5.

put with continued saline infusion; if urinary output decreases, then furosemide or mannitol may

improve renal function. Benadryl (diphenhydramine hydrochloride, manufactured by ParkeDavis, Morris Plains, N.J.) may be useful for treating hives and itching.

The donor unit should be reexamined for compatibility with the blood type of the recipient as

well as for evidence of infection, loss of package

integrity, hemolysis, and, in winter, freezing, which

can cause hemolysis. The suspected reaction and its

management should be annotated both on the

casualty’s field aid card and in the transfusion log;

if possible, the unit of blood should be transferred

with the casualty during evacuation to the next

echelon of care.

TRANSFUSION SUPPORT AT THE THIRD AND FOURTH ECHELONS

Because blood transfusion is an integral part of

surgery, third- and fourth-echelon facilities perform all aspects of transfusion therapy with PRBCs

described for second-echelon facilities. Third- and

fourth-echelon facilities have improved laboratory

and blood banking capability, and are responsible

for more complex transfusion practices (Table 15-

4). Some third-echelon, and all fourth-echelon facilities may be required to support surgery with

random-mix instead of universal-donor group O

PRBCs (see Tables 15-1 and 15-2). Compared with

the use of group O universal-donor PRBCs, the use

of random-mix blood greatly increases the risk of

transfusion reactions and requires testing of the

recipient’s blood group—with attendant delays in

therapy as well as increasing the requirement for

laboratory testing. Random-mix blood must only

be used with trained and tested personnel in authorized laboratories. Some experienced military clinicians13 argue strongly that only group O universaldonor PRBCs should be available within the entire

combat zone; this, however, is not present doctrine.

Support with frozen blood and other blood products such as platelets and FFP may also be authorized. Finally, third- and fourth-echelon units are

authorized by doctrine to perform emergency collection and transfusion of blood that is collected in

the field when blood products are unavailable

through regular channels.

Logistical Aspects

The requirements for liquid PRBCs have already

been described. Additional blood banking capa-
Anesthesia and Perioperative Care of the Combat Casualty

352

bility for military medical facilities in the Department of Defense’s Deployable Medical Systems

(DEPMEDS) configurations is determined by the

blood bank section. The Liquid Blood Bank Medical

Material Set (MMS) D304 can store 500 units of

PRBCs, and can perform ABO grouping, Rh typing,

and a single-tube (major-side saline, immediate

spin) cross-match on each patient. The Liquid/

Frozen Blood Bank MMS D404 has the same capacity for liquid PRBCs as the MMS D304, but can also

store 485 units of frozen PRBCs, 10 units of FFP, and

5 units of platelets (each unit of platelets contains

six platelet packs). The MMS D404, when fully

staffed and supplied, should be capable of reconstituting 180 units of frozen PRBCs in 24 hours. Both

blood bank sections should be able to issue up to 250

units of banked PRBCs in 24 hours, and are authorized to collect and type 180 units of fresh whole

blood for extreme emergencies.10 (See Chapter 6,

Deployable Hospitals, for a more complete discussion of MMSs and their use in DEPMEDS-equipped

hospitals.)

The use of frozen red blood cells allows large

amounts of universal-donor blood to be prepositioned at military medical facilities outside the continental United States (OCONUS), which has the

theoretical potential to minimize long supply lines

from CONUS. However, frozen red blood cells

require storage in –80°C freezers, as well as large

volumes of sterile crystalloid, special processing

equipment, trained personnel, and, after being

thawed, at least 1 hour per unit to process for

deglycerolization. After they are thawed, frozen

red blood cells have a shelf life of only 24 hours;

however, this time may be extended under emergency military conditions to 72 hours.20 Although

future research may improve the utility of frozen

blood, at present these factors may limit its use in

forward locations.20,21 Frozen blood remains an

integral part of doctrine. Medical officers assigned

to areas that utilize frozen blood resources should

be especially careful to start early, hands-on planning and realistic training to determine the system’s

clinical utility.

Platelets require storage at 20°C to 24°C with

continuous gentle agitation, and have a 5-day viable shelf life after collection. One unit of FFP

contains one unit of all clotting factors per milliliter,

and must be stored at –18°C or colder. FFP has a

shelf life of 12 months when stored at this temperature and must be administered within 24 hours after

being thawed. Given these constraints, the availability of FFP and, especially, platelets may be limited in the combat zone.9

Effect of Massive Transfusion

Resuscitation and surgery of the severely

wounded casualty may require large amounts of

blood. Massive, large-volume transfusions can rapidly reduce a medical treatment facility’s blood

supplies. This may also lead to subsequent difficulties in patient management, including dilutional

coagulopathy and selection of appropriate blood

group for further transfusion. The management of

a dilutional coagulopathy is described in Chapter

14, Transfusion Therapy.

The subsequent transfusion management of the

patient who survives surgery with massive transfusion requires that attention be paid to both the

patient’s ABO blood group and the blood group of

the units previously transfused.22 Patients with A,

B, or AB blood groups who have received more than

4 units of group O whole blood, or 8 units of group

O PRBCs, should be transfused with group O blood

if further transfusions are needed for at least 2

weeks or until their serum is compatible with the

donor blood type as determined by a full compatibility test.22,23

Emergency Collection and Transfusion of Whole

Blood Donated in the Field

Collection and transfusion of fresh, whole blood

in the field (authorized by doctrine at third- and

fourth-echelon facilities under emergency conditions

only) is a source of platelets, plasma, and red blood

cells. Because whole blood contains plasma with

antibodies to the antigens not present on the donor’s

red blood cells, it is necessary to do full ABO group

determination on both the donor’s and the recipient’s

blood. The principles involved in performing an

emergency collection of whole blood in the field are

outlined in Exhibit 15-3.

When performing an emergency collection, a key

factor is the potential risk of infection. Infections

may be caused by viruses (such as the human immunodeficiency virus, parvovirus, or hepatitis) or

other organisms (such as those that cause malaria or

syphilis) transmitted via the donor’s blood, or bacterial skin flora contracted by the use of improper

sterile technique. Sterility is best ensured by using

(a) Betadine Solution (povidone-iodine, 10%, manufactured by Purdue Frederick, Norwalk, Conn.) to

scrub the donor’s arm and (b) the appropriate collection technique. Blood must be collected into a

sterile, closed, blood-collecting and -dispensing bag.

Because blood is a fertile culture medium, small

amounts of contaminating bacteria may grow rap-
Military Transfusion Practice

353

EXHIBIT 15-3

EMERGENCY COLLECTION AND TRANSFUSION OF BLOOD DONATED IN THE FIELD

This collection and transfusion technique should be used in extreme emergencies after all efforts to obtain

adequate supplies of blood collected by blood banks have failed. Emergency collection should never be

performed in lieu of securing blood through normal channels. Although the following information is provided

so that the technique can be performed as safely as possible in this contingency, the emphasis should be on

careful planning to obtain an adequate supply of blood-bank-procured blood.

Donor Factors

Lab tests for transmissible infection may not be available in the field. Careful screening of a donor’s risk for

infection is thus essential. Strongly consider recruiting volunteers who were active blood bank donors prior to

deployment—their blood and their risk for infection will have been checked repeatedly during that period.

Recognize that military units may place pressure on their members to donate; give a donor a chance to decline

in private in case he or she is unwilling to admit to potentially risky behavior. Donations may be obtained every

6 to 8 weeks from healthy male donors. After donating, the donor should be given oral fluid replenishment and,

if possible, light duty for 12 to 24 hours. Donors screened in the field should be questioned regarding the

following topics:

• history of intravenous drug use,

• history of hepatitis,

• history of high-risk sexual behavior,

• exposure to malaria, dengue fever, or recent febrile illness,

• prior blood transfusion, and

• prior or current pregnancy.

Collection Factors

Scrupulously scrub the donor’s vein with Betadine Solution (povidone-iodine, 10%, manufactured by

Purdue Frederick, Norwalk, Conn.). The collecting unit is a closed system, with a measured amount of sterile

anticoagulant and preservative already in place. A volume of 450 to 500 mL should be collected. The unit of

whole blood should be cooled immediately and used as soon as possible. Assign the collected unit an

identification number, and enter the number in the blood log. A tube of serum from the donor should be saved

indefinitely for future testing and tracking. The appropriate supplies, listed below, must be available in

advance:

• blood collection sets;

• Betadine swabs to sterilize the collection site;

• appropriate markers to label and identify the collected unit;

• typing sera for groups A and B blood, which must be kept cool with blood in the refrigerator;

• glass slides, mixing swabs, wax pencils, and lab slips;

• purple-top blood tube (containing ethylehediaminetetraacetic acid [EDTA] anticoagulant); and

• red-top tube for serum sample.

Transfusion Factors

Transfusion of whole blood must be fully ABO specific because the plasma in the donor’s blood may have

high levels of antibodies to the recipient’s antigens. (Universal-donor group O whole blood, as used in the

Korean and Vietnam wars, was checked to ensure that the antibody titer was not elevated prior to shipment to

a combat zone.) Full blood typing, with determination of Rh, and cross-matching should be performed on both

the donor unit and the recipient.

idly, especially if the unit is warm and not used

immediately. Thus, scrupulous sterile technique is

essential, and the collected unit should be labeled,

cooled, and used as soon as possible. The collected

unit should (a) be given a unique unit-identification

number (eg, the social security number of the donor) and (b) be added to the blood inventory and

disposition records.
Anesthesia and Perioperative Care of the Combat Casualty

354

Currently, laboratory tests to screen the donor

unit for infectious diseases are not available in the

field setting, although some may be developed in

the near future. Questions to determine the donor’s

potential risk for transmissible infections (eg, a history

of drug use, high-risk sexual behavior, hepatitis, or

recent febrile illness) are thus critical to selection of

the safest donor in a field environment. Current policy

mandates that a sample tube of serum from the

donor be retained and stored for future testing and

tracking if necessary. The physician should also

consider a potential donor’s time in country and possible exposure to endemic disease such as malaria.

The individuals who can most safely donate are those

who give a negative response to these questions and

who have been successfully screened and used as

regular blood donors prior to deployment. Although there will be heavy peer pressure on potential donors to provide blood for their wounded

comrades, they should be given a chance to decline

in private, according to procedures established in

civilian blood banks. Again, the technique of emergency collection and transfusion of whole blood

should only be used under dire circumstances when

there is absolutely no other source of blood and

when the casualty would die without transfusion.

MILITARILY UNIQUE CONSIDERATIONS

The administration of group-specific blood,

proper use of identity tags, and clinical relevance of

the Rh blood group for female casualties pose challenges for military physicians in the combat zone.

Research is active and the development of new

products and technology can be anticipated. Integration of these factors into appropriate planning

and training exercises is critical to successful military transfusion practice.

Group-Specific Transfusion and Random-Mix

Blood

Universal-donor group O PRBCs are the optimal

resuscitation fluid for a combat casualty; however,

the supply may be limited in a combat zone. Liquid

group O PRBCs comprise only 50% of blood collected and shipped to a combat zone. Because

second-echelon units are authorized by doctrine to

receive only group O PRBCs, the supply of universal-donor group O PRBCs may be more limited at

third- and fourth-echelon units, and may become

limited at second-echelon facilities during peak

demand for blood.

Group-specific transfusion refers to blood that is

matched on the basis of the donor’s and the

recipient’s ABO groups alone. Random-mix blood

refers to a supply of PRBCs that has been collected

from donors of all blood groups. Administration of

group-specific, random-mix blood requires correct

determination of the recipient’s ABO blood group

and the correct administration of the appropriate

unit to the recipient. In contrast, group O PRBCs

may be transfused in an emergency without regard

for either testing the recipient24,25 or matching the

appropriate unit with the recipient.

The determination of the recipient’s blood group

and the safe transfusion of random-mix blood under combat or mass casualty conditions, even with

the laboratory capability of a fourth-echelon tertiary facility, require extensive, careful planning

and training. The potential risks and logistical

problems may be understood by considering the

nature of the ABO blood groups.

The ABO blood groups are named for the antigen

or antigens that are present on the surface of red

blood cells (Figure 15-6).26 Shortly after birth, we

develop immunoglobulin (Ig) M antibodies directed

against the antigen or antigens that are not present

on our own red blood cells. Thus, individuals with

group O blood have neither the A or the B antigen

present on their red blood cells, but have antibodies

against both A and B antigens in their plasma. Individuals with group A blood have only the A antigen

present on the red cells, and have antibodies to the

B antigen in the plasma. These IgM antibodies are

present shortly after birth and efficiently activate

complement when combined with antigen. An ABOmismatched transfusion is immediately life-threatening and may cause hemolysis, hemoglobinuria,

hypotension, renal failure, and death.19

Group O PRBCs, which comprise approximately

40% to 50% of the blood supply, can safely be

infused into casualties of any ABO blood group

regardless of the recipient’s blood group. Group O

whole blood, which was used as universal-donor

blood during World War II and the Korean and

Vietnam wars, can also be safely infused if special

laboratory techniques demonstrate that the donor

plasma (which is infused with the unit of whole

blood) does not have high-titer anti-A or anti-B

antibodies.5,12 However, transfusion of whole blood

or PRBCs of the A, B, and AB blood groups can only

be given to casualties who have these same blood

antigens present on their red cells. Thus, transfusion of PRBCs of any blood group other than O
Military Transfusion Practice

355

ABO Frequency and Compatibility

Blood Type

Frequency in Population 45% 10% 40% 5%

Antibodies Anti-B Anti-A Anti-B and Anti-A No Antibodies

IgM Present from Infancy

A

A B

B A

O

B B

Red Cell Antigens

Can Donate Packed Cells to: A, AB B, AB Universal Donor (A, B, AB, O) AB

Can Receive from Transfusion: A, O B, O O Universial Recipient

(A, B, O, AB)

Fig. 15-6. The nature of blood and the ABO blood groups.

A B AB

A

requires knowledge and confirmation of both the

recipient’s and the donor’s blood groups.

Identification Tags

Determination of blood groups for identification

tags (ie, dog tags) is not done in medical laboratories, and there may be a 3% to 6% error rate in either

the ABO or the Rh blood groups,27 although a recent

study28 indicates that the risk may be lower. During

World War II, however,

when blood had to be given in emergencies in

forward hospitals and tests for compatibility were

impractical, the blood group of the recipient had

to be accepted on the basis of his identification tag,

in which the known error was from 5 to 25

percent.12(p429)

Previously, these percentages of error had been

acknowledged in the context that dog tags were

designed only to identify potential donors and were

not designed to be used for transfusions on individual patients.12,27 However, even contemporary

medical officers who are unfamiliar with this philosophy may assume that identity tags are provided

to guide transfusions without confirmatory testing,

as World War II–era medical officers did:

Circular Letter No. 170, Office of The Surgeon General, War Department, Services of Supply. In this

letter [dated 2 December 1942], it was pointed out

that the policy of blood grouping of military personnel and its purpose seems to have been misunderstood by some medical officers.... [T]he assumption that the first [dog tag or identification tag]

typing test would be the only one performed was

based on a false premise. To correct the misconception it was pointed out again that the purpose of the

program was to simplify assembling donors whose

blood would probably crossmatch with that of intended recipients.12(p235)

. . . .

Our physicians were amazed to learn, well into

development of our blood program, that the error

rate in dog tags was as high as 5–10%, and that dog

tags were not designed to be a field expedient

means to transfuse random mix blood. We also

found that we did not know the blood type for

civilian casualties.29

In addition, civilian casualties will not have identity tags, which further illustrates the inappropriateness of using identity tags for type-specific blood

transfusion.

Finally, identity tags may be used in the future in

second-echelon facilities, which use universal-donor group O PRBCs, to match the Rh group of the

casualty with that of the donor unit (this subject is

discussed in greater detail later in this chapter).

Priority for Rh-negative blood will be given to female casualties.30 This strategy would (a) decrease

exposure and sensitization of Rh-negative female

casualties to Rh-positive blood, (b) represent a significant change in the doctrinal use of identity tags,
Anesthesia and Perioperative Care of the Combat Casualty

356

and (c) require improved testing capability and

further education and training.

Female Casualties and Rh Blood Groups

Military medical officers must carefully consider

the relevance of the Rh blood group system and the

different clinical implications of Rh-mismatched

blood transfusions when administered to male or to

female combat casualties. The Rh blood groups and

antibodies differ clinically from those in the ABO

system; they were not identified until more than 30

years after discovery of the ABO blood groups,

when they were determined to be the major cause of

hemolytic disease of the newborn. Approximately

85% of the population is Rh positive; 15% is Rh

negative.31 Acute intravascular hemo-lytic reactions in Rh-mismatched transfusions are rare, because antibodies formed against Rh antigens are

IgG, and unlike IgM–ABO antibodies, do not activate complement efficiently. Additionally, these

IgG antibodies appear in Rh-negative patients only

after exposure (ie, sensitization) to Rh-positive blood

and are not present from birth like the antibodies to

ABO antigens. Sensitization occurs most frequently

in Rh-negative women after exposure to the blood

of an Rh-positive fetus at childbirth. Rh-mismatched

transfusion reactions are thus usually not immediately life threatening, and are manifest by chronic,

extravascular hemolysis that appears several weeks

after exposure to Rh-positive blood. However, unlike ABO antibodies, these IgG antibodies do cross

the placenta, and, in the Rh-positive fetus of an Rhnegative, previously sensitized mother, will cause

chronic extravascular hemolysis or hemolytic disease of the newborn (Figure 15-7).

Thousands of Rh-negative male combat casualties have been transfused with Rh-positive blood

without clinically significant consequences.5,12 There

is a much smaller experience with transfusion of

Rh-mismatched blood to female civilian trauma

casualties,32,33 including cases that have resulted in

legal action.34 In the future, medical officers will

likely care for more female casualties in combat.

Some major clinical factors that should be considered are discussed in Exhibit 15-4.

Active Research Efforts

A major goal of military research is to develop

blood products for field use, thus providing essential support for resuscitation of the wounded

soldier immediately or within the first few hours

after the injury is sustained. The research and

development for such products is being conducted

in universities, by the American Red Cross, and in

Fig. 15-7. The consequences of administering Rh-positive

blood to Rh-negative women are not immediately apparent but neither are they benign. This third-trimester fetus

died of chronic hemolytic disease of the newborn, which

occurs in Rh incompatibility when an Rh-positive fetus is

conceived in an Rh-negative, but sensitized, mother. The

immunoglobulin G antibodies in the mother’s blood cross

the placenta and cause chronic hemolysis with

hyperbilirubinemia and enlargement of the fetus’ bloodforming organs. Antibodies to Rh groups form only after

an Rh-negative individual is exposed to Rh-positive blood.

This occurs most commonly in women after they give

birth to an Rh-positive child. Sensitization and antibody

formation will also occur in Rh-negative battlefield casualties

who receive transfusions of Rh-positive blood. Owing to the

relative frequency of Rh-negative individuals in the general population, Rh-mismatched blood transfusions have

been given widely in prior wars; however, the casualties

were male. In both men and sensitized women, the immediate consequences of an Rh-mismatched transfusion are

clinically mild and at the time of future surgery can be

managed routinely with modern blood banking techniques. However, women who are sensitized will be at

risk for severe complications of pregnancy in an Rhpositive fetus. Photograph: Courtesy of Colonel John

Pierce, MD, Medical Corps, US Army; Chief of Pediatrics,

Walter Reed Army Medical Center, Washington, DC.
Military Transfusion Practice

357

EXHIBIT 15-4

TRANSFUSION SUPPORT OF FEMALE COMBAT CASUALTIES: CLINICAL IMPORTANCE

OF THE RH BLOOD GROUP

Universal-donor blood is used for resuscitation in the field.

Blood typing and cross-matching are not feasible in forward combat mass casualty situations. Universaldonor transfusions, defined as group O without Rh specificity, have been safe and effective when administered

to male casualties in prior conflicts. During World War II, experience with multiple Rh-incompatible

transfusions demonstrated that serious reactions to Rh-incompatible blood were rare in men, although the

survival of incompatible red cells was poor.1 In Vietnam, over 100,000 universal-donor transfusions were given

without a single fatal reaction.2

Rh-positive blood is used in universal donor transfusions.

All group O units shipped to Korea were Rh positive.1 Group O, Rh-negative blood was distributed to fixed

hospitals in Japan. This policy was developed to maintain Rh-negative blood at facilities with the capability to

identify Rh-negative individuals and to prevent further transfusions with Rh-incompatible units. Current

doctrine does not discriminate between Rh-positive and Rh-negative group O units distributed for universal

transfusion at forward units. Thus, 85% of all units transfused in these areas will be Rh positive.

Women deployed to forward combat units who require transfusion may therefore receive Rh-incompatible blood.

Using manpower data from the Persian Gulf War3 and current military doctrine,4,5 up to 10% of universal

donor transfusions given to female casualties are predicted to be Rh incompatible (ie, Rh-positive blood is

transfused into an Rh-negative recipient).

Rh-incompatible transfusions in women can be less efficacious and cause anti-Rh antibodies that

compromise future pregnancies.

Approximately 35% of deployed women have been pregnant.3 If sensitized, Rh-incompatible cells will

survive poorly in these women and cause a delayed transfusion reaction. Virtually any Rh-negative patient

transfused with Rh-positive blood develops anti-Rh antibodies. IgG anti-Rh antibodies can cross the placenta

during future pregnancies and cause severe, fatal consequences to the fetus.

The risk of transfusing Rh-incompatible blood to women can be minimized.

Based on the supply of O-negative blood and the number of expected female casualties, adequate stocks of

O-negative blood should be available to transfuse most female casualties who receive universal-donor transfusions. In the future, development of hemoglobin-based oxygen carriers, enzymatic removal of Rh antigen from

stored liquid red cells, or improved logistical aspects of frozen group O, Rh-negative blood may decrease the

incidence of Rh-incompatible blood transfusion. At present, in situations where a casualty’s Rh blood group

cannot be determined, reserving Rh-negative units whenever possible for transfusion to women will not expose

men to any more danger than in prior wars but will limit the dangers involved to women. Department of

Defense policy is now being revised to call for using identity tags to match the blood type and Rh factor of the

donor unit and the recipient in forward mass casualty situations where universal-donor group O blood is used.6

NOTE: identity tags should never be used to match the ABO blood group of donor and recipient.

(1) Kendrick DD. Blood Program in World War II. Washington, DC: Department of the Army, Medical Department, Office of

The Surgeon General; 1964: 748. (2) Camp FR, Conte NF, Brewer JR. Military blood banking 1941–1973: Lessons Learned

Applicable to Civil Disasters and Other Considerations. Fort Knox, Ky: US Army Medical Research Laboratory; 1973. (3)

Scheflen KC. Defense Manpower Data Center, Monterey, Calif. Personal communication, 21 April 1990. (4) Scotti MJ,

chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs. Fort Detrick, Frederick,

Md: Defense Medical Standardization Board; 1990. (5) Rosenblatt MS, Hirsch EF, Valeri RC. Frozen red blood cells in combat

casualty care: Clinical and logistical considerations. Milit Med. 1994;159:392–397. (6) Joseph SC, Assistant Secretary of

Defense (Health Affairs). Policy for the Use of ID Tags and ID Cards for Emergency Transfusion at the Second Echelon of Medical

Care and the Validation of Those Parameters. Washington, DC: Department of Defense. Memorandum for Secretaries of the

Military Departments, Chairman of the Joint Chiefs of Staff, 21 April 1995.

Exhibit prepared for this textbook by Janiine Babcock, MD, Major, Medical Corps, US Army; Blood Research Detachment,

Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Anesthesia and Perioperative Care of the Combat Casualty

358

the commercial sector, as well as through research

programs in the U.S. Army and the U.S. Navy. An

essential ingredient for the rapid success of these

efforts is close communication among these

organizations so that appropriate information

can be shared and duplication of effort does not

occur.

Current efforts are mainly directed toward improving the shelf life and storage properties of

PRBCs or developing a blood substitute to simplify

the use of blood on the battlefield. Other efforts are

directed toward improving early hemostasis and

improving access to platelets and other blood products at third- and fourth-echelon areas (Exhibit 15-5).

Some of these goals may be met without developing

new technology by adapting existing technology to

the field environment. One method could be the

use of portable blood pheresis units to produce

platelets and FFP without removal of the donor’s

red blood cells (Figure 15-8 and Exhibit 15-6).

EXHIBIT 15-5

DEVELOPMENT OF BLOOD PRODUCTS FOR FUTURE FIELD USE

The following blood products and specific component therapies are being developed for field use:

Hemoglobin-Based Oxygen Carriers

A temporary replacement for red cells in the field may be hemoglobin-based oxygen carriers. These might

be prepared in solutions of 10% virally inactivated hemoglobin that has been cross-linked to avoid the

dissociation of the 64-kd tetrameric form into 32-kd dimers, which can induce renal failure. The hemoglobin

can be purified from human red blood cells or produced in a recombinant form; hemoglobin that has undergone

polymerization in addition to cross-linking (or that has been encapsulated in liposomes) appears to have a

prolonged survival time in the circulation and to have reduced vasoactivity. Thus, multiple products or forms

of hemoglobin may eventually be licensed. Such products, which are being produced by at least four

companies, are in phase I or phase II clinical trials in the United States and abroad. Hemoglobin-based oxygen

carriers could presumably be used in liquid form in the second echelon; perhaps, for ease of storage, they could

also be prepared in lyophilized form as well.

Platelets

The short, 5-day dating period for platelets, as well as the requirement that they be maintained at 22°C with

continuous gentle agitation, precludes their use in far-forward positions. The ideal platelet preparation would

be one that could be virally inactivated and then (a) lyophilized under controlled conditions and (b) reconstituted and infused. Alternatively, platelet concentrates could be stored indefinitely in a frozen form utilizing

nontoxic cryoprotectants; they could then be thawed and directly infused into recipients.

Fibrin Sealant

Fibrin sealant comprised of purified, virally inactivated human fibrinogen and human thrombin is now

commercially available in Europe and Canada, although the product has not been approved for use in the

United States by the U.S. Food and Drug Administration. Fibrin sealant could be used on the field, delivered

on bandages to control massive bleeding from organs such as the liver or spleen or from open wounds. Such

preparations in cruder form were actually used successfully during World War II. Once such preparations are

licensed, their use will undoubtedly be extended to many types of surgical situations.

Plasma

Plasma that has undergone viral inactivation by pasteurization or by solvent detergent treatment is now

available in other countries. Such plasma could be prepared in freeze-dried form and then reconstituted in the

field for treatment of casualties.

Modifications in Red Blood Cell Storage

Efforts are being made to extend the survival of PRBCs up to 6 to 8 weeks after collection, thus allowing

longer storage time after reaching their destination in the theater of operations. Additional research efforts

include (a) prolonging the storage time of frozen cells that have undergone deglycerolization and (b) converting

the Rh(D) antigen to produce Rh-negative cells.

Exhibit prepared for this textbook by Barbara Alving, MD, Colonel, Medical Corps, US Army; Chief, Department of

Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Military Transfusion Practice

359

EXHIBIT 15-6

HEMOPHERESIS: A FUTURE SOURCE OF PLATELETS IN THE FIELD?

The need for platelets during contingencies is small; however, there are times when platelets are required

to save lives. Because platelets have only a 5-day storage life, it is very difficult to transport them from the

continental United States to other parts of the world within the time allowed. Current research is investigating

ways to extend the shelf life of platelets to longer than 5 days (see Exhibit 15-5), although final development

and licensure by the U.S. Food and Drug Administration may take years.

In the meantime, the only way to provide platelets in the field has been emergency donor collections of

whole blood at field hospitals. This form of collection has increased risks due to the inability to pretest the

donors for transfusion-transmitted diseases, and many donors must be available to provide enough platelets

for even one casualty.

To minimize the need for this form of collection and to alleviate risks and reduce stress, the U.S. military is

studying the possible use of portable plateletpheresis capabilities for use in the field. Today’s technology has

plateletpheresis machines that are very light (55 lb), durable, and easy to transport. One plateletpheresis donor

unit has the equivalent of platelets obtained from six to eight regular whole-blood donors. This scheme has

several advantages:

• Pretested donors can be ready to donate, allowing for a safer product.

• Fewer donors are required, as plateletpheresis donors can donate every 3 to 7 days, compared with 8 weeks

for regular blood donors.

• A superior product is provided, virtually free from red blood cells and more concentrated, reducing possible

inadvertent hypervolemia.

The disadvantages include the following:

• Laboratory technicians must be trained to do plateletpheresis, which is a time-consuming and expensive

process.

• Approximately 1.5 to 2 hours per patient is required for each plateletpheresis donation.

A concept that may possibly be used in the future is having plateletpheresis capability on hospital ships and

at army blood supply units. These units would then supply other third- and fourth-echelon hospitals with

platelets when emergency situations require.

Fig. 15-8. Collection of platelets with

a portable pheresis unit from a volunteer donor in a Department of Defense Deployable Medical Systems

(DEPMEDS) environment. Approximately 2 hours are required for the

donation. The pheresis unit uses generator power and is the size of a medium-sized television set. A volume

of platelets equivalent to a six-pack

was collected from this single donor,

but the red blood cells were returned.

Platelets can be collected in this fashion every 2 weeks.
Anesthesia and Perioperative Care of the Combat Casualty

360

PLANNING AND TRAINING

A successful military transfusion program must

blend operational, clinical, and blood-distribution

system factors (Figure 15-9), each of which requires

consideration of these three critical elements:

1. education of personnel, with hands-on,

realistic training,

2. review of doctrine in FM 8-55 and other

manuals, and

3. real-time interaction with the blood-distribution system before and during the deployment.

Detailed guidelines for interacting with the military blood-distribution program have been prepared for this textbook; these are included at the

end of this chapter.

Adjustments From Civilian Medicine

The needs and practices of military medicine

require that medical officers make both a philosophical and a clinical adjustment (Figure 15-10).

After they have been educated, leaders should review doctrine and incorporate blood product management into their training exercises.

Leaders from prior wars with experience in planning and training for a military blood transfusion

Fig. 15-10. Military hospital and field transfusion environments. (a) The poster describes safe transfusion practice in the

hospital; after the medical officer orders the blood, the entire process is handled by other medical personnel such as nurses

and laboratory workers. (b) In the resuscitation tent of a clearing station, the medical officer will not have access to the hospital

personnel who routinely handle the blood (as indicated in the poster). When medical officers move from the hospital to the

field, they must adjust not only to the changes in physical environment but also to the absence of these personnel.

Fig. 15-9. Planning and training for a successful military

transfusion program. Operational, clinical, and blooddistribution program factors must blend together

smoothly and should be incorporated into all training

exercises.

Operational

Considerations

Blood-Distribution

Program

Clinical

Factors

Successful Blood

Transfusion

in the Field

a b
Military Transfusion Practice

361

program have described the philosophical and clinical readjustments they found necessary as they made

the transition from civilian to military medicine:

Division clearing stations are not emergency rooms.

Ambience is different, triage is different, problems

are different. The rules must be different and the

reasons for this must be part of the indoctrination

of the medical officers in the combat zone and the

pathologists who operate the blood supply.13

. . . .

[From World War II:] Intravenous therapy (transfusion therapy) is a medical specialty, training in

which is not provided in a routine medical education.... [T]he civilian physician, if all goes smoothly,

is completely unaware of the organization and

painstaking control that make the use of parenteral fluids safe. When, however, he enters the

Medical Corps, he is called upon to practice more

intravenous therapy than he employed in civilian

life.... Military medicine presents special problems

in intravenous therapy as compared with civilian

practice: the incidence of shock, hemorrhage, and

burns is many times greater, as is their severity.

In their treatment, the methods of civilian medicine must be modified by considerations of transport, equipment, and environment.... If a medical

officer were to attempt to accumulate a store

of whole blood, he would find that none of the

methods in use in civilian practice could be applied directly to his military problem without

modifications.12(p77)

. . . .

[From the Persian Gulf War:] Modern physicians

Fig. 15-11. Hands-on practice with

second-echelon blood transfusion.

Soldiers of B Company, 307th medical battalion, 82nd Airborne division,

practice their division-level blood

transfusion program. The “combat

casualty” is simulated.

don’t handle blood.... It has become so specialized

that physicians (clinicians) have lost experience

dealing with blood. The contemporary technical

information available on blood management was

focused largely on theater and corps hospital blood

receipt and storage.14

Hands-On Practice: Lessons Learned, Lost, and

Learned Again

Hands-on training at the patient level is critical

to the successful implementation of military transfusion practice (Figure 15-11). Medical personnel

should walk through demonstrations that simulate

transfusing blood to mock casualties in realistic

training situations, including mass casualty exercises. Blood and the appropriate supplies should be

taken to the field during training, and all daily

inspections, inventories, and reports performed.

The senior medical officer at the Second-Brigade

Clearing Station during the Persian Gulf War (1990–

1991) recalls:

We maintained a blood capability in our clearing

station for a 3-month period before the ground war

started. Our resupply of blood was frequently random-mix, with expiration dates only a few days

from the date of our receipt. Our biggest advantage

was having practiced a random-mix scheme at division level, and knowing that it was highly unsatisfactory; we therefore insisted on group O blood,

often returning to the blood-supply unit several

times to obtain it.

When I returned to the 82nd as Division Surgeon

less than 3 years after the Persian Gulf War, medics
Anesthesia and Perioperative Care of the Combat Casualty

362

had already stopped practicing with blood because

it was not “safe.” During one exercise, I noted that

the blood was in our forward (alpha) echelon; however, the infusion sets were in our second (bravo)

echelon. The soldiers who had done the packing

had never administered a unit of blood.

For our airfield seizure role at present, our planning is much simpler: we jump in with group O

blood in ice and melted water in Styrofoam boxes.

There is occasionally some difficulty obtaining

blood prior to jumping, but not so much as during

the Persian Gulf War because now we are the only

game in town.35

And during Operation Restore Hope in Somalia

(1993), an emergency blood drive was performed to

obtain plasma and platelets for a patient who was

hurt in a vehicle accident. The 86th Evacuation

Hospital laboratory personnel did an excellent job

and saved a life. In their afteraction review, they

stated that they were not as well trained as they

should have been but understood that it is difficult

to train for specific emergency conditions. They

also stated that trying to collect blood at a time of

extreme emergency, with little time, is very difficult

and stressful, especially when there also are increased

demands placed elsewhere in the laboratory.36

A Second-Echelon Transfusion Strategy

Figure 15-12 depicts a strategy that was developed for transfusion of blood for male and female

casualties in the 82nd Airborne division during the

Persian Gulf War.37 At this time, division clearing

stations were supported by the 307th medical battalion and could be augmented with a forward

surgical support team. At the onset of deployment,

group O PRBCs were in short supply, and division

units frequently received random-mix blood. Initially, an A/O system, as had previously been used

in Vietnam, was chosen, owing to a shortage of

Transfuse

Confirm casualty’s gender

Confirm that donor

unit is Type O

Male casualty:

Release Type O,

Rh-positive blood

Female casualty:

Release Type O,

Rh-negative blood

Release Type O Blood

Record unit number in log

Record data in lab

transfusion log

Complete transfusion request

form (miscellaneous lab slip)

O Phase

Fig. 15-12. This second-echelon blood transfusion program was developed for men and women in the 82nd

Airborne division during the Persian Gulf War. Group O

packed red blood cells (PRBCs) were used. In this setting,

no determination of the recipient blood group was necessary. Data were recorded and the unit transfused. Women

were to receive Rh-negative blood and men Rh-positive

blood. When universal-donor blood was not available in

the early stages of the deployment, and only random-mix

blood was available, an A/O phase was planned. After

practicing the A/O system, division medical companies

carried only group O blood and used the system illustrated here. The A/O system, which was intended to be

reserved for use only in emergencies, was never actually

used.
Military Transfusion Practice

363

EXHIBIT 15-7

NEW POLICY FOR USING IDENTIFICATION TAGS AND CARDS FOR EMERGENCY

BLOOD TRANSFUSION AT THE SECOND ECHELON

On 21 April 1995, the Assistant Secretary of Defense for Health Affairs issued a memorandum for the

secretaries of the military departments and the chairman of the joint chiefs of staff to establish new Department

of Defense policy for transfusing Rh-negative blood and for using identification tags and cards for secondechelon blood transfusions:

Effective immediately, during contingencies, the Services will provide Rh negative packed red cells to Rh negative male

and female patients based on the Rh blood type on their ID tag or card at the second echelon of medical care. Third

echelon and higher level of care medical treatment facilities have the capability and are expected to group, type and

crossmatch blood with group specific Rh negative packed red cells selected for both Rh negative female and male

patients prior to transfusion. Priority of Rh negative blood for transfusion should be given to Rh negative females if

shortages of Rh negative blood arise. This new policy will also reduce the same sensitization to Rh negative males,

although the impact of sensitization on males and the health care system is not as great.

With implementation of the above policy and as a result of acceptable high error rates of the ABO group and Rh type

placed on ID cards and tags, it is imperative that the Services review their procedures for verifying and validating that

the ABO group and Rh type on each service member’s ID tags and cards matches laboratory testing results as

documented in each service member’s medical records. These procedures should also require that this verification be

performed during the processing just prior to deployment.

The Services are to implement this policy immediately and provide their plans for verifying and validating service

members’ ID tags and cards concerning blood groups and types within 60 days of the date of this memorandum.

Reprinted from Joseph SC. Assistant Secretary of Defense (Health Affairs). Policy for the Use of ID Tags and ID Cards for

Emergency Transfusion at the Second Echelon of Medical Care and the Validation of Those Parameters. Washington, DC: Department

of Defense. Memorandum for Secretaries of the Military Departments, Chairman of the Joint Chiefs of Staff, 21 April 1995.

universal-donor PRBCs for use at the division level.

We decided to transfuse female casualties with Rhnegative blood and to use Rh-positive blood in

males, as had been practiced previously.

Since this deployment, new policy is being established to transfuse group O PRBCs to casualties at

the second-echelon, according to the Rh group on

their identity tags (Exhibit 15-7).30

The chief value of this system was that it gave a

structure for practice. Although the A/O system appeared simple in theory, the added complexity of (a)

performing a single slide test for the A antigen on the

recipient’s cells and (b) correctly assigning the result

of the test to a casualty in a resuscitation tent greatly

increased the risk of a transfusion reaction and slowed

the pace of patient care—even when practiced under

controlled training conditions. All units in the division, therefore, vigorously pursued a supply of group

O PRBCs. The A/O system was reserved as an emergency back-up system but was never used.

Planning at the Third and Fourth Echelons

Although third- and fourth-echelon facilities

have improved blood banking capabilities, planning and training are just as critical to a successful

transfusion policy in these facilities as they are at

the second echelon. The clinical environment

may vary considerably according to the location

and operational situation where the hospital is

deployed. Two personal experiences relate different blood banking procedures (Exhibits 15-8 and

15-9). The transfusion practice in each setting

was successful because the clinical policies were

tailored for the operational setting, and the personnel were familiar with policies because their

preparation, planning, and training had been extensive.

SUMMARY

blood banking industry shortly after World War II.

Since then, transfusion medicine has become increasingly sophisticated and specialized, and physicians in peacetime medicine are no longer trained

Treatment of battlefield injuries with blood transfusion in an operational environment is a cornerstone of military medicine. The practice has saved

thousands of lives and gave rise to the civilian
Anesthesia and Perioperative Care of the Combat Casualty

364

EXHIBIT 15-8

PREPARING BLOOD BANKS FOR MASS CASUALTY INCIDENTS

(1) Sandler SG, Sharon R, Hermoni D, Superstein E. Blood transfusion therapy in the rear hospital during the Yom Kippur War

(October 1973). Milit Med. 1977;141:49, 52–53. (2) Sandler SG. Strategies for blood services in mass casualty incidents. In:

Cowley RA, Edelstein S, Silverstein M, eds. Mass Casualties: A Lesson Learned Approach. Accidents, Civil Disorders, Natural

Disasters. Washington, DC: US Department of Transportation. 1982: 229–233. DOT HS 806 302; October 1982. Proceedings,

First International Assembly on Emergency Medical Services; June 1982. (3) Sandler SG. Blood utilization during the October

1973 (Yom Kippur) war. Presented at Combat Casualty Care Research Program; US Army Medical Research Development,

Acquisition and Logistics Command (Provisional); 8–9 November 1993; Fort Detrick, Frederick, Md. (4) Camp FR, Conte NF,

Brewer JR. Military Blood Banking 1941–1973: Lessons Learned Applicable to Civil Disasters and Other Considerations. Fort Knox,

Ky: US Army Medical Research Laboratory; 1973. (5) Kendrick DD. Blood Program in World War II. Washington, DC:

Department of the Army, Medical Department, Office of The Surgeon General; 1964. (6) Standard E5.000/Tests intended to

prevent disease transmission. In: Standards for Blood Banks and Transfusion Services. 16th ed. Bethesda, Md: American

Association of Blood Banks; 1994: 14.

Exhibit prepared for this textbook by S. Gerald Sandler, MD, Professor of Medicine and Pathology, and Director, Blood Bank

and Blood Donor Service, Georgetown University Medical Center, Washington, DC 20007.

Fourth-echelon and other military general hospitals should be capable of providing blood bank services that are

comparable to those of a civilian medical center. In a mass casualty incident, these services should include protocols

for the selection of blood products for massive transfusions, positive blood-sample identification systems, a complete

blood-component service, and procedures for the releasing of un–cross-matched universal-donor blood.

The following guidelines, based on previous military and civilian experiences,1–5 are intended to provide a

framework for addressing these issues.

Protocols for Managing Severe Blood Loss

Past experiences indicate that in mass casualty situations, physicians are likely to request the same quantities and

types of blood products that they have become accustomed to using in the management of similar cases.1,2 For this

reason, protocols that are intended to be used during a mass casualty incident should be implemented in advance as

part of routine operations. The concept of stockpiling special blood products, blood substitutes, or plasma expanders

to be used only in a mass casualty incident introduces the risk of delays while clinicians accommodate themselves to

unfamiliar clinical responses and reactions.

Separate Donor-Related and Casualty-Related Services

In a mass casualty incident, the blood bank staff should be unencumbered by blood-donor and -supply problems

and should focus their efforts on providing safe, serologically compatible blood products in a timely manner. The

current standard of practice in civilian and military hospitals requires all blood products intended for transfusion to

be tested for multiple infectious disease markers, including anti–human immunodeficiency virus and hepatitis B

surface antigen.6 The former practice of collecting units of blood at the hospital and transfusing them as ABO-matched,

but otherwise untested, warm blood is outdated and is not recommended.

Ideally, all blood donor–related functions should be conducted in a separate facility that is sufficiently distant from

the hospital to allow a surge of blood donors to respond to the incident without congesting access to the hospital. The

distinct functions of a hospital transfusion service (eg, cross-matching, blood typing) compared with a blood-donor

service (eg, phlebotomy, infectious-disease testing, component preparation) should be recognized in the planning

process. The optimal result would be a physical separation that would allow each service to conduct its specialized

functions without competing for resources.

Positive Identification Systems

A system that positively identifies each casualty, blood sample, and blood product intended for transfusion is

essential for safe management of a mass casualty incident. Wristband systems with uniquely numbered sticky labels

are marketed commercially and have been used successfully by civilian transfusion services in a wide range of

emergency situations.

Universal-Donor Blood and Abbreviated Cross-Matching

The blood bank should have a standing operating procedure that defines the requirements for releasing group Opositive (or O-negative) universal-donor blood without a cross-match. Criteria should also be specified for switching

from the standard 60-minute cross-match to an abbreviated 5- to 15-minute cross-match. If group O whole blood or

fresh frozen plasma is transfused to a group A or B recipient, then guidelines should be specified for safe reversion to

ABO group-specific red blood cell transfusions.
Military Transfusion Practice

365

EXHIBIT 15-9

BLOOD BANKING IN AN ISOLATED THEATER OF OPERATIONS: EXPERIENCE OF THE

46TH COMBAT SUPPORT HOSPITAL, MOGADISHU, SOMALIA, 1993

Background

• Blood supply system: from Armed Services Whole Blood Processing Laboratory (ASWBPL), Maguire Air

Force Base, New Jersey. Daily reports submitted. Routine shipments arrived weekly. About 72 hours from

request to delivery of blood products.

• Available blood products:

° random-mix packed red blood cells (liquid)

° fresh frozen plasma; about one fourth to one half of bags cracked and unsuitable for use after rewarming

° platelets not available

• Inventory: started with 50 units of packed red blood cells, increased to 200 units

• Blood banking personnel:

° one M-4 blood bank–qualified technician

° one laboratory officer

° no pathologists or blood bank fellowship–trained officers

• Nearest civilian hospitals: Cairo, Egypt, and Nairobi, Kenya

• Emergency collection of whole blood: blood was drawn only when the demand was expected to increase.

The donation and collection systems were kept separate from the dispensing function of the blood bank.

Training and Preparation

Civilian mass casualties were treated at least weekly. All aspects of trauma medicine were exercised,

including the blood bank and the use of whole blood. After treatment, all aspects of trauma care, including the

blood bank, were reviewed and improved if needed. The following amounts of blood were administered from

30 September through 4 October 1993:

Date Incident or Injury Blood Products Administered

30 September Shark bite, one casualty > 50 units of fresh frozen plasma and packed red

blood cells; > 20 units of fresh whole blood, type O

2 October Land mine exploded under a jeep; > 20 units of fresh whole blood, type O; Rh-negative

four casualties, including one blood used for the woman

woman

3–4 October Rangers pinned down after a > 70 units of fresh whole blood, type O

failed raid in Mogadishu; > 20

casualties

Impressions

The use of whole blood maintained a reserve inventory of ASWBPL blood products. Surgeons preferred

whole blood to component therapy, especially as platelets were not available. Hemostasis was subjectively

improved. All blood donors had been tested for antigens to the human immunodeficiency virus prior to

deployment, but (a) identifying potential donors in advance of deployment and (b) having access to field test kits

for blood-borne pathogens would have been useful.

Exhibit prepared for this textbook by (1) Denver Perkins, MD, Colonel, Medical Corps, US Army; Director for Clinical

Services 46th Combat Support Hospital; Assistant Chief of Anesthesia, Walter Reed Army Medical Center. (2) David Elliot,

MD, Lieutenant Colonel, Medical Corps, US Army; Chief of Surgery 46th Combat Support Hospital; Chief of Critical Care,

Walter Reed Army Medical Center. (3) Hector Velasquez, Captain, Medical Service, US Army; Chief Laboratory Officer

46th Combat Support Hospital, Chief of Clinical Microscopy, Walter Reed Army Medical Center, Washington, DC

20307-5001.
Anesthesia and Perioperative Care of the Combat Casualty

366

in nor practice routine blood banking skills. The

complex principles of transfusion support of civilian trauma patients in a fixed facility with a modern

blood bank are detailed in Chapter 14, Transfusion

Therapy. However, military casualties, wounded

in a dangerous, austere environment, continue to

suffer from injuries that require blood product

therapy. There is increasing emphasis on moving

resuscitation and surgery even farther forward on

the battlefield with mobile surgical teams. In addition, military personnel continue to be deployed to

isolated areas lacking access to fixed facilities with

modern blood banking resources. Thus, the ability

to bring these resources as safely as possible to

forward and remote areas in an operational emergency military situation remains imperative.

This chapter describes the theory and practice of

the unique aspects of military transfusion medicine. Emphasis is on planning and training, becoming familiar with military terms and doctrine, integrating operational and clinical factors with the

blood-supply system, and making the adjustment

from the civilian clinician’s relative isolation from

the laboratory and the blood bank. Medical officers

must understand the availability of blood products

according to doctrine and the echelons of care so

they can anticipate the clinical needs of casualties—

from resuscitation to definitive surgery and postoperative care. Technical factors related to the safe

operation of a small emergency blood bank in the

field must be mastered by clinical personnel who

may be unfamiliar with their peacetime use.

The frequency of the ABO and Rh blood groups

in the general donor population acquire unique

military significance, and the immediate and delayed effects of massive transfusion occur frequently.

The treatment of female casualties in the field poses

additional unique military considerations and is

mandating further changes in doctrine, which include the proper use and interpretation of identity

tags.

Blood products have a finite shelf life and require

special storage, handling, and monitoring, which

may limit their use in a rapidly evolving operational scenario. Thus, research is active in the areas

of developing a blood substitute, controlling hemorrhage early on the battlefield with products such

as fibrin glue, and providing platelet support.

Most importantly, successful military transfusion medicine requires practice and planning. The

learning curve is steep and cannot be mastered for

the first time on actual casualties. Leaders should

use blood products as realistically as possible during training exercises. Early interaction with the

blood-supply system is critical. Only when clinical,

technical, and operational factors are recognized

early and then practiced can medical officers safely

provide blood products and meet what should be

the standard of care for emergency treatment of

men and women injured in battle.

Acknowledgments

The authors thank Colonel William H. Crosby, Medical Corps, U.S. Army (ret); Colonel Robert J. T.

Joy, Medical Corps, U.S. Army (ret); Colonel Louis Diehl, Medical Corps, U.S. Army, Walter Reed

Army Institute of Research and Walter Reed Army Medical Center; the personnel of the 307th Medical

Battalion and the 82nd Airborne Division, who developed the division’s blood policy during the

Persian Gulf War; Colonel Craig Llewellyn, Medical Corps, U.S. Army (ret); Captain Evan Renz,

Medical Service, U.S. Army; Commander Kevin Yeskey, U.S. Public Health Service; Captain Gerald

McGlothlen, Medical Service Corps, U.S. Navy Reserves; Commander David Reichman, Medical

Service Corps, U.S. Navy; and Colonel Anthony Polk, Medical Service, U.S. Army (ret), Director,

Armed Services Blood Program Office, during the Persian Gulf War.

REFERENCES

1. Robertson LB. A contribution on blood transfusion in war surgery. Lancet. 1918;1:759–762.

2. Beecher HK. Preparation of battle casualties for surgery. Ann Surg. 1945;121:769–792.

3. Crosby WH, Howard JM. The hematologic response to wounding and to resuscitation accomplished by large

transfusions of stored blood: A study of battle casualties in Korea. Blood. 1954;9:439–460.
Military Transfusion Practice

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4. Heaton LD. Foreword. In: Kendrick DD. Blood Program in World War II. Washington, DC: Department of the

Army, Medical Department, Office of The Surgeon General; 1964.

5. Kiel F. Development of a blood program in Viet Nam. Milit Med. 1966;131:1469–1482.

6. Churchill ED. Surgeon to Soldiers. Philadelphia, Pa: JP Lippincott; Philadelphia, Pa: 1972: 36–58.

7. Frishberg DP. Historical review: Highlights in the development of combat transfusion programs. Journal of

Military Medical Laboratory Science. 1989;18:41–44, 66–71.

8. Crosby WH. World War II’s war within a war: What delayed the delivery of whole blood to overseas combat

troops. MD. 1991;Dec:35–39.

9. US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA; approved

final draft January 1994. Field Manual 8–55.

10. Scotti MJ, chairman. Defense Medical Standardization Board. DEPMEDS Policies/Guidelines: Treatment Briefs.

Fort Detrick, Frederick, Md: Defense Medical Standardization Board; 1990.

11. Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians:

Instructor Manual. 5th ed. Chicago, Ill: American College of Surgeons; 1993.

12. Kendrick DD. Blood Program in World War II. Washington, DC: Department of the Army, Medical Department,

Office of The Surgeon General; 1964: 406, 443, 634, 635.

13. Crosby WH. Colonel, Medical Corps, US Army (ret). Personal communication, September 1994.

14. Gerber FE. Employment of the 307th Medical Battalion (Airborne) in Operations Desert Shield and Desert Storm: A

Personal Experience. Carlisle, Pa: US Army War College, Military Studies Program; May 1992. Monograph.

15. Ryden SE, Oberman HA. Compatibility of common intravenous solutions with CPD blood. Transfusion.

1975;15:250–255.

16. Walker RH, ed. Blood transfusion practice. In: Technical Manual. 11th ed. Bethesda, Md: American Association

of Blood Banks; 1993: 421.

17. Bickell WH, Matthew MJ, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients

with penetrating torso injuries. N Engl J Med. 1994;331:1105–1109.

18. Jacobs LM. Timing of fluid resuscitation in trauma. N Engl J Med. 1994;331:1153–1154. Editorial.

19. Walker RH, ed. Adverse effects of blood transfusion. In: Technical Manual. 11th ed. Bethesda, Md: American

Association of Blood Banks; 1993: 471.

20. Rosenblatt MS, Hirsch EF, Valeri RC. Frozen red blood cells in combat casualty care: Clinical and logistical

considerations. Milit Med. 1994;159:392–397.

21. Crosby WH. Frozen blood for military transfusion service. Milit Med. 1967;132:119–121.

22. Crosby WH, Akeroyd JH. Some immunohematologic results of large transfusions of group O blood in recipients

of other blood groups: A study of battle casualties in Korea. Blood. 1954;9(2):103–116.

23. Barnes A, Allen TE. Transfusions subsequent to administration of universal donor blood in Vietnam. JAMA.

1968;204:695–697.

24. Walker RH, ed. Pretransfusion testing. In: Technical Manual. 11th ed. Bethesda, Md: American Association of

Blood Banks; 1993: 312.
Anesthesia and Perioperative Care of the Combat Casualty

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25. Walker RH, ed. Blood grouping and typing. In: Technical Manual. 11th ed. Bethesda, Md: American Association

of Blood Banks; 1993: 621.

26. Walker RH, ed. ABO, H, and P blood groups. In: Technical Manual. 11th ed. Bethesda, Md: American Association

of Blood Banks; 1993: 203–228.

27. Gaydos JC, Cowan DS, Polk AJ, et al. Blood typing errors on US Army identification cards and tags. Milit Med.

1988;153:618–620.

28. Ensign BG, Dougherty TH, Bowlus IN, Konecki EA. ABO and Rh blood type errors on Air Force identification

cards. Milit Med. 1995;160(6):288–290.

29. Jaques D. Lieutenant Colonel, Medical Corps, US Army; Senior Medical Officer, 307th Medical Battalion, 82nd

Airborne, Persian Gulf War; Chief of Surgery, Department of Surgery, Walter Reed Army Medical Center,

Washington, DC. Personal communication, June 1994.

30. Joseph SC, Assistant Secretary of Defense (Health Affairs). Policy for the Use of ID Tags and ID Cards for Emergency

Transfusion at the Second Echelon of Medical Care and the Validation of Those Parameters. Washington, DC:

Department of Defense. Memorandum for Secretaries of the Military Departments, Chairman of the Joint Chiefs

of Staff, 21 April 1995.

31. Mollison PL, Engelfriet CP, Contreras M, eds. The Rh blood group system. In: Blood Transfusion in Clinical

Medicine. 9th ed. Boston, Mass: Blackwell Scientific Publications; 1992: 543–591.

32. Lefebre J, McLellan BA, Coovadia AS. Seven years experience with group O unmatched packed red blood cells

in a regional trauma unit. Ann Emerg Med. 1987;16:1344–1349.

33. Schmidt PJ, Leparc GF, Samia CT. Use of Rh positive blood in emergency situations. Surg Gynecol Obstet.

1988;167:229–233.

34. Engle HL. Medicolegal considerations in transfusion medicine. In: Petz LD, Swisher SN, eds. Clinical Practice of

Transfusion Medicine. 2nd ed. New York, NY: Churchill Livingstone; 1989: 355–362.

35. Clark J. Major, Medical Corps, US Army. Senior Medical Officer, 2nd Brigade Clearing Station, 82nd Airborne

Persian Gulf War. Division Surgeon 82nd Airborne. Personal communication, December 1994.

36. Kozar M. First Lieutenant, Medical Service, US Army. Laboratory officer, 86th Evacuation Hospital, Mogadishu,

Somalia. Personal communication, May 1995.

37. Bolan CD, Strawder G. 82nd Airborne Division blood policy. In: Gerber FE. Employment of the 307th Medical

Battalion (Airborne) in Operations Desert Shield and Desert Storm: A Personal Experience. Carlisle Pa: US Army War

College, Military Studies Program; May 1992. Monograph.
Military Transfusion Practice

369

GUIDELINES FOR INTERACTING WITH THE BLOOD-DISTRIBUTION SYSTEM

Crossing the bridge between the medical officers who treat the casualties and the blood-distribution system that

supports them takes planning, coordination, and teamwork. The successful blood product distributions that we have

had recently in operations other than war and during combat operations are due largely to the foresight, hard work,

and sacrifice of many people. They have read and understood the history of the use of blood products, have actually

played a part in making the system work, have used blood products in battlefield conditions, and have seen the

miracles that blood provides. Above all, we must teach from these lessons of history in order to train as a team, train

as realistically as possible, and then train again so that we are always prepared.

All medical officers who work in a field environment where they will be transfusing blood products must

understand the Armed Services Blood Program (ASBP) blood-distribution system (Guidelines Exhibit 1). Interestingly, the adoption of a permanent ASBP evolved from lessons learned from the Korean War, where

[n]o single medical item was more important than blood, and its supply was a specialized program stretching from the zone

of the interior to the battlefield.1(p243)

. . . .

At the end of World War II, well-founded, detailed recommendations for a transfusion service had been prepared and

submitted through channels to the proper authorities. Time, manpower, effort, money, and lives could all have been spared

in Korea if these recommendations had been utilized as a basis for postwar planning. As it was, the newly developed plans

were not ready for implementation when the Korean combat began.2(p xiii)

The existence of an ASBP and its blood-distribution doctrine has since provided excellent support—from the

Vietnam War, to the Persian Gulf War, to Operation Uphold Democracy (1994) in Haiti. Blood products were used in

each of these operations. What has changed are the amounts and types of blood products as well as the transfusion

procedures. This trend will also continue as new blood products and possible blood substitutes become licensed.

As important as support to the blood program, however, is the fact that the who, what, where, when, and how change

for every operation and situation. Thus, prior planning and coordination as well as training are required to make

things work as they should. The medical officer at the field medical treatment facility (MTF) or the forward medical

company must be aware that blood products will not suddenly appear at their facility. For the system to work, the

medical team must plan for and request blood products through the right communications and coordination channels.

Who Should Medical Officers Talk to When Blood Products Are Required?

The chain of command is always the main communication channel for making things happen. Commanders are

responsible for what happens in their units. Good commanders also realize that they are not expert in everything. They

defer to lawyers on legal issues, to logisticians on logistical issues, and should also should defer blood-distribution and

technical blood issues to the blood expert.

Once he has coordinated the medical officer’s requirements with the blood expert, the commander will usually

allow the two to communicate directly, requiring status updates to keep himself informed.

At certain levels of command, the commander will have a Surgeon’s staff. The commander will appoint or designate

a person to be the blood program officer. For example, a Joint Blood Program Officer (JBPO) can be found at each

Unified Command Surgeon’s Office. JBPOs are usually laboratory officers who are specialists in blood banking and

are well trained in the blood-distribution system. These blood program officers are directly involved with planning

the blood-distribution system for operations within their unified command.

Depending on its size or based on the operation, the unified command may designate Area Joint Blood Program

Officers (AJBP0s). These officers are used quite often with Joint Task Forces (JTFs) and work for the JTF Surgeon. They

plan, coordinate, and communicate in much the same way as the JBPO but within a much more defined geographical

area. They, too, are laboratory officers specialized in blood banking procedures. They are good assets for answering

any blood-distribution questions that arise. Their main purposes are to

• monitor blood requirements from treatment facilities within their designated area,

• coordinate deliveries of blood products to those facilities, and

• report to the JBPO as well as their respective command element.

The AJBPO is responsible for making sure the blood-distribution system is working. The AJBPO is also responsible

for monitoring blood-supply units (BSUs) and blood transshipment centers that provide storage of blood products for

further shipment to MTFs.

BSUs are designated in the operations plans or orders. They can be an army blood platoon, a marine fluids platoon,

a fixed MTF, a medical ship offshore, or a field MTF. They are designated specific missions depending on their

capabilities. They will usually have a laboratory officer who may or may not be specialized in blood banking.
Anesthesia and Perioperative Care of the Combat Casualty

370

Guidelines Exhibit 1 continues

1. Each medical treatment facility (MTF) or element, including a naval vessel, that requires blood

products submits a daily blood report (BLDREP) to a designated unified command component bloodsupply unit (BSU). The MTF may be located in the second, third, or fourth echelon of medical support.

2. Each designated unified command component BSU issues blood products to the requesting MTFs. If

directed, a BSU may serve MTFs of more than one service. The BSU may be located in the third or

fourth echelon of medical support.

3. Each component BSU submits a daily BLDREP to a designated Area Joint Blood Program Office

(AJBPO).

4. Each blood transshipment center (BTC) or transportable blood transshipment center (TBTC) issues

blood products to each designated component BSU based on daily allocation guidelines established

by the AJBPO or, if no AJBPO exists, the Joint Blood Program Office (JBPO).

5. Each BTC or TBTC submits a daily BLDREP to the designated AJBPO.

6. Each AJBPO manages blood products between component BSUs and submits a daily BLDREP to the

JBPO.

7. The JBPO manages blood products between blood program areas in the unified command and

submits a daily BLDREP to the Armed Services Blood Program Office (ASBPO).

8. The ASBPO directs the designated Armed Services Whole Blood Processing Laboratory (ASWBPL) to

ship blood products, based on the ASWBPL situation report (ASWBPLSITREP).

9. Each ASWBPL ships blood products to designated unified command BTC or TBTC.

10. Military blood donor centers (BDCs) in the continental United States (CONUS) ship blood products

to resupply designated ASWBPLs as directed by the respective Service Blood Program Office (SBPO).

Defense Logistics Agency contracts with civilian blood agencies are activated when Armed Services

Blood Program shortfalls are experienced.

11. Prepositioned frozen blood products stored in unified command armed services blood product

depots (BPDs) are issued to BSUs as directed by the JBPO.

12. The JBPO provides, on a continuous basis, information on the status of the theater blood program to

the unified command surgeon, who, in turn, coordinates with the Joint Staff.

13. The ASBPO is chartered to ensure implementation of the Armed Services Blood Program polices

established by the Assistant Secretary of Defense for Health Affairs, and to coordinate the provision

of blood products to the unified commands in concert with the Joint Staff. The U.S. Army is the

Executive Agent for the ASBPO. An ASBPO situation report (ASBPOSITREP) is provided in

accordance with mobilization plans.

GUIDELINES EXHIBIT 1

ARMED SERVICES BLOOD-DISTRIBUTION SYSTEM: OPERATIONAL DESCRIPTION

Blood product requirements are preplanned and established in each unified command operations plan. The

daily blood report (BLDREP), which includes a request for blood products and the status of the inventory,

activates the execution of those plans. Information copies of the BLDREP and the blood shipment report

(BLDSHIPREP) are provided in accordance with local command operational plans. The blood-distribution

system is the standard doctrine. However, it is very flexible and, based on the situation, changes can be made

with coordination with the Armed Services Blood Program Office (ASBPO). The numbers inside the boxes

correspond to the numbered guidelines below.
Military Transfusion Practice

371

US Air Force MTF

1

US Army MTF

1

US Navy MTF

1

US Navy Ships MTF

1

2nd Echelon MTF

1

DMSO 2nd Echelon

1

US Marine Corps

BSU 2, 3

BPD

11

Unified Command

JBPO

7, 11, 12

AJBPO

6

BTC

4, 5

TBTC

4, 5

SUPPORTING BASE

THEATER OF OPERATIONS

ASBPO

8, 13

AWBPL

9

US Army SBPO

US Air Force SBPO

US Navy SBPO

10

US Air Force

10

US Army BDC

10

US Navy BDC

10

Civilian BDC

10

Coordination Blood Flow

AJBPO: Area Joint Blood Program Office

ASBP: Armed Services Blood Program

ASBPO: Armed Services Blood Program Office

ASBPOSITREP: ASBPO situation report

ASWBPL: Armed Services Whole Blood Processing Laboratory

ASWBPLSITREP: ASWBPL situation report

BDCs: blood donor centers

BLDREP: blood report

BLDSHIPREP: blood shipment report

BPD: blood product depot

BSU: blood supply unit

BTC: blood transshipment center

CONUS: continental United States

JBPO: Joint Blood Program Office

JTF: Joint Task Forces

MTF: medical treatment facility

POC: point of contact

SBPO: Service Blood Program Office

TBTC: transportable blood transshipment center

Reports

BSU

2, 3

Joint Staff

12, 13
Anesthesia and Perioperative Care of the Combat Casualty

372

However, they are trained to store and distribute blood products to MTFs. They are usually the MTF’s and the medical

officer’s prime point of contact to the blood-distribution system.

So medical officers need to know that they will be supported by a BSU, who is monitored by an AJBPO, who reports

to a JBPO within the unified command. These players in the blood-distribution system need to be able to communicate

directly.

How Do Medical Officers Communicate With Their Points of Contact?

Once medical officers know who their direct points of contact are, how do they communicate their blood

requirements? The Department of Defense has standardized message formats so that each service can communicate

with the other services. Two of these standardized messages are the blood report (BLDREP) and the blood shipment

report (BLDSHIPREP).

Each MTF is required to submit a daily BLDREP to its supplier of blood products. This report can be sent by the

fastest means of communication available. In some situations, this can be by courier. In other situations, telephones,

radios, or satellite communications may be used. This report can also be sent by the message center nearest the MTF.

The means by which the report is sent is dictated by the communications capabilities that exist within the MTF and

within the supporting communications network.

A standard BLDREP will provide the facility’s current blood inventory, the amount of blood products required

within the next 12 to 48 hours, the amount of blood that will expire in the next 7 days, and the estimate of blood products

required in the next 7 days. It may give the location of the MTF, and it has a narrative section to address any problems

and to provide any other information required by higher commands. For example, transfusions may be addressed by

stating the blood-unit donor number, matched to the patient transfused by the casualty’s social security number.

A standard BLDSHIPREP will alert the receiver of blood products as to when a blood shipment will be arriving. It

will also provide the number of blood products being shipped, by their ABO group and Rh type. If the shipment is

arriving by air, it will usually have a mission number and a transportation control number to specify which plane the

blood products will be arriving on. It will give the shipper’s address and the point of contact.

Examples of BLDREPs and BLDSHIPREPs, with codes for using these reports, are explained in Planning for Health

Service Support3 and Health Service Support Logistics in Joint Operations.

4 It is imperative that medical officers who require

blood products for their facilities make sure that their staffs are trained on the exact procedure to follow when

submitting these reports.

How Do Medical Officers Receive Their Blood Products?

The best part of the blood-distribution system is that it has at its service all the transportation capabilities that the

Department of Defense has available. The problem is that these resources can become limited. Therefore, communication of requirements and coordination of transportation assets becomes very important.

Fortunately, this blood-distribution system is used daily for peacetime transportation of blood products around the

world. Thus, personnel involved especially with the strategic lift capabilities are always ready to implement

contingency blood-distribution procedures. Medical officers must realize that because strategic lift is limited, good

coordination of blood requirements with sufficient advanced notice is also required.

Tactical transportation capabilities are also sufficiently flexible to meet requirements. Blood products can be

shipped directly to the MTF (ie, unit distribution) or MTF personnel may have to go to a specific location to receive their

blood products (ie, point distribution). In these routine instances, wheeled vehicles (assets organic to the unit) are

used. Problems arise when distance, terrain, security, and time become factors.

When wheeled-vehicle transport is not useful, helicopters fill the void. Medical-evacuation helicopters have a

secondary mission to ship blood products forward to MTFs. Helicopter support to ships that receive casualties needs

to be coordinated. Helicopters can carry blood products via sling-load when more blood is required than can be held

within the helicopter.

When helicopter capability is limited due to security, distance, and increased demands, tactical airlift via aircraft

such as C-130s must be coordinated well. The JBPOs and AJBPOs should know these capabilities and be able to

coordinate shipments as required. It is their responsibility to coordinate these capabilities for the MTFs.

When Can Medical Officers Get Blood From the Armed Services Blood Program?

Each of the military’s different types of operations is unique as to when the MTFs will require blood products.

Medical officers may find themselves involved in a forward surgical element that is being deployed as part of the first

wave of assault troops. In this case, the medical officer will need to deploy with blood products. In other cases, the

medical officer may deploy with an MTF that will be deployed in a second iteration of troop movements and will not
Military Transfusion Practice

373

have to take on casualties until days after entering the area of operations. In this case, it would not be reasonable to

deploy with blood products; rather, they should be requested just before casualties are expected. In all cases, the

medical officer needs to ask these questions: When is the blood required? and When can I get it?

The blood-distribution system can accommodate the treatment facilities as long as there has been coordination and

advanced notice. For example, the Joint Task Force Surgeon for Operation Uphold Democracy was able to bring

players together prior to the operation to plan all aspects of the medical support. Major Noel Webster, from the Armed

Services Blood Program Office, was able to meet with the 82nd Airborne Division Surgeon, Lieutenant Colonel Jeffrey

Clark, to coordinate some of the Division’s unique requirements for blood support. Major Webster gave him some

recommendations, and points of contact (POCs) were established to set up the distribution system. The POCs worked

agreements among themselves, and Lieutenant Colonel Clark had the POCs train and exercise the distribution prior

to deploying to make sure any problems were identified and resolved. When the 82nd Airborne Division was ready

to deploy, all systems were go and the blood was ready and prepared without a hitch.

In other circumstances, the JBPO would be the POC coordinating the planning prior to and during an operation. For

example, the U.S. Central Command (CENTCOM) Surgeon’s JBPO, Commander Barbara Fieldman, was heavily

involved in identifying BSUs for supporting medical treatment during the Persian Gulf War. In this operation, MTFs

did not have to deploy with blood; instead, a blood-distribution infrastructure of BTCs and BSUs was in place to

provide blood products for them. Commander Fieldman coordinated with the MTF commanders personally to make

sure they were being supported.

REFERENCES

1. Crowley AE. The Medics’ War: United States Army in the Korean War. Washington, DC: Center of Military History, US Army;

1987: 243.

2. Kendrick DD. Preface. In: Blood Program in World War II. Washington, DC: Department of the Army, Medical Department,

Office of The Surgeon General; 1964: xiii.

3. US Department of the Army. Planning for Health Service Support. Washington, DC: Headquarters, DA; approved final draft,

January 1994. Field Manual 8-55.

4. Joint Chiefs of Staff. Joint Tactics, Techniques, and Procedures for Health Service Support Logistics in Joint Operations. Washington,

DC: US Departments of the Army, Navy, Navy US Marine Corps, and Air Force; initial draft 15 August 1993. Joint Pub 4-20.1.
Neurological Injuries

375

Chapter 16

NEUROLOGICAL INJURIES

JEFFREY M. BERMAN, M.D.*; JOHN F. BUTTERWORTH IV, M.D.†; AND DONALD S. PROUGH, M.D.‡

INTRODUCTION

THE NATURE OF HEAD INJURIES SUSTAINED IN COMBAT

GOALS OF NEUROSURGICAL INTERVENTION

PATHOLOGICAL ANATOMY AND PHYSIOLOGY OF TRAUMATIC BRAIN

INJURY

Closed Brain Injury

Penetrating Brain Injury

Enhanced Vulnerability to Secondary Ischemic Brain Injury

Systemic and Organ-System Responses

CARE OF THE PATIENT WITH TRAUMATIC BRAIN INJURY

Initial Care

Anesthetic Management

Management in the Intensive Care Unit

MEDICAL COMPLICATIONS OF HEAD TRAUMA

RECOVERY AND OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY

SPINAL CORD INJURY

Physiological Responses

Initial Care

Anesthetic Management

Management in the Intensive Care Unit

Medical Complications

SUMMARY

*Captain, Medical Corps, U.S. Navy Ready Reserve; Instructor of Anesthesia, Department of Anesthesia, Bowman Gray School of Medicine,

Medical Center Boulevard, Winston-Salem, North Carolina 27157-1009

†Associate Professor of Anesthesia and Vice Chairman for Research, Department of Anesthesia, Bowman Gray School of Medicine, Medical

Center Boulevard, Winston-Salem, North Carolina 27157-1009

‡Captain, Medical Corps, U.S. Navy Ready Reserve; Professor and Chairman, Department of Anesthesiology, The University of Texas Medical

Branch, 301 University Boulevard, Galveston, Texas 77555-0591
Anesthesia and Perioperative Care of the Combat Casualty

376

INTRODUCTION

Traumatic brain injury is classified as open or

closed. Closed head trauma is further subdivided

into severe (characterized by prolonged coma; ie,

inability to obey simple verbal commands), moderate (either requiring craniotomy or producing coma

of short duration), and minor (neither requiring

surgery nor resulting in coma). Because of the

enormous economic and social toll exacted by vehicular trauma, closed head injury, which is a common cause of death after civilian blunt trauma, has

been extensively studied in patients and in experimental models. Open head injury, which is more

relevant to military trauma, has been studied much

less well. Therefore, many of the principles of

nonoperative management of penetrating brain injury are based on the assumption that knowledge

gained from clinical or experimental closed brain

injury can be extrapolated to injuries caused by

penetrating missiles. One central assumption is

that secondary brain injury—an often-preventable

consequence of hypotension, hypercarbia, hypoxemia, or intracranial hypertension—contributes

heavily to death or disability caused by the original

injury.1,2

Penetrating injuries to the spinal cord do not play

a large role in military medicine: most casualties

whose spinal cords are transected are killed when

the missile (bullet or fragment) continues on its

path and injures nearby organs (eg, the heart and

great vessels, liver, spleen). In addition, data gathered during the Vietnam War by the Wound Data

and Munitions Effectiveness Team (WDMET) indicate that 98% of soldiers with gunshot wounds of

the cervical spine that included the cord were fatally injured.3 Closed injuries to a soldier’s spinal

cord are not different from those that occur to civilians, and occur for the same reasons (eg, blunt

trauma due to vehicular accidents and falls). There

are far more casualties with brain than spinal cord

injuries; furthermore, the chances that therapeutic

intervention will effect improved results are greater

with brain than with spinal cord injuries. For these

reasons, most of this chapter pertains to traumatic

brain injury; spinal cord injury is treated much less

extensively.

This chapter discusses the perioperative care of

the neurologically injured patient as it is practiced

today in medical centers. Because the equipment

and facilities found in the Department of Defense’s

Deployable Medical Systems (DEPMEDS) hospitals

replicate to some extent the sophistication of civilian trauma centers, we have included descriptions

of state-of-the-art systems and management techniques. However, we also provide practical suggestions for use when advanced support systems

are not available.

THE NATURE OF HEAD INJURIES SUSTAINED IN COMBAT

Combat casualties with head trauma will present

with either open or closed injuries. In open injuries,

the scalp is lacerated and the bone is fractured,

usually with significant depression, thereby exposing the dura; this in turn is usually lacerated, exposing the cortex, which is almost invariably damaged

as well. Closed head injuries may or may not

involve laceration of the scalp, but if a laceration is

present, the calvarium either will be uninjured or

will have no more than a simple, nondepressed,

linear fracture. In most cases of closed head injury,

there is no scalp laceration or skull fracture at all.

Combat casualties with head trauma can also be

classified as having either blunt or penetrating injuries, depending on the mechanism of injury. Blunt

trauma usually results in closed injuries, while penetrating wounds are almost always open. In the

combat zone, the overwhelming majority of battle

casualties with head trauma have penetrating missile wounds made either by fragments from explosive munitions or bullets fired by small arms. Most

of the latter wounds are open in the sense that the

dura has been lacerated and the cranial contents are

exposed. When closed injuries due to blunt trauma

occur in the combat zone, they are usually due to

accidents not related to hostile action. Such casualties are classified as having nonbattle injuries.

Penetrating missile wounds of the head are extremely lethal. WDMET data from the Vietnam War

indicate that the probability of being fatally

wounded by a missile—either fragment or bullet—

that hit the skull was close to 4 out of 5 (Chapter 1,

Combat Trauma Overview, discusses the WDMET

data more fully). Bullet wounds to the head made

by assault rifles were fatal in about 95% of cases.3

Combat casualties with penetrating head trauma

who survive to reach a deployable hospital fall into

two categories: (1) most commonly, a small fragment wound, with injuries to one cerebral lobe; or

(2) less commonly, a tangential gunshot wound, in
Neurological Injuries

377

which the bullet causes a depressed skull fracture,

which, in turn, actually lacerates the dura and the

brain. Depending on how deeply the bullet has

penetrated into the intracranial compartment, it

may or may not, in and of itself, directly injure the

brain parenchyma. Neurosurgical practice in the

combat zone consists of managing both these categories of casualties and those with multiple lobe

injuries, such as those caused by bullets. These

casualties are in addition to those who demonstrate the spectrum of closed injury, which can

range from transient loss of consciousness to

deep coma.

Given the dismal outcome of penetrating missile

wounds to the head, preventive measures such as

protective helmets have long been recognized to be

of great importance. The presently fielded military

helmet will stop most fragments produced by improved fragmentation munitions as well as certain

types of bullets fired from pistols (Figure 16-1).

Fielded helmets will rarely stop a bullet fired from

a rifle or machine gun unless the bullet’s performance has been severely degraded by passing

through a solid object (such as another casualty),

has ricocheted off an object and is traveling sideways, or is at the end of its trajectory (1,000 m or so)

(Figure 16-2).

During the Persian Gulf War, the Kevlar helmet was found to be extremely beneficial and

was associated with a significant diminution of

open head injuries, compared to what would

have been expected and considering the number

of injuries seen to other parts of the body, particularly when compared to the number of injuries to the face and eyes.4 For this reason, we

might well expect that in future conflicts (in which

explosive munitions are the predominant source

of penetrating missiles, as they were during the

Fig. 16-1. The protection provided by Kevlar helmets is

impressive: this helmet, seen close up, was struck by an

0.45 ACP (automatic Colt pistol) at a range of 3 m. The

defeated bullet is shown on the left; an unfired bullet is

shown on the right. By way of contrast, the 9 x 19-mm

Parabellumround will usually perforate a Kevlar helmet.

Photograph: Wound Ballistics Laboratory, Letterman

Army Institute of Research, Presidio of San Francisco,

Calif.

Fig. 16-2. Both sides of this Kevlar helmet have been

perforated by a 5.45-mm bullet (fired by an AK74 at range

of 3 m), which entered from the viewer’s left. Notice the

mushroomlike mass of disrupted Kevlar at the site of

the bullet’s exit. Kevlar fibers have been found lining

tissue wound tracts in experimental ballistic studies.

Photograph: Wound Ballistics Laboratory, Letterman

Army Institute of Research, Presidio of San Francisco,

Calif.
Anesthesia and Perioperative Care of the Combat Casualty

378

Persian Gulf War), a greater percentage of hospitalized casualties will have closed rather than

open head injuries.

Casualties who have sustained closed head

injuries and survive to reach the hospital level

often suffer more significant brain injury than do

those who have sustained open injuries. This is

due, in part, to the fact that open injuries generally allow some decompression of the immediately surrounding cerebral substance through the

break in the skull. In closed injuries, in contrast,

the additional volume of blood clot and cerebral

swelling must be accommodated within the space

of the bony intracranial compartment, which does

not change in volume. Therefore, the brain tissue

itself is subjected to the total obligatory compression (aside from the small amount that is accommodated by the vessels and the ventricles).

In addition, the physical factors that determine whether an injury will actually break the

calvarium are generally associated with a more

focal and less diffuse distribution of kinetic energy. The injury is, therefore, usually greater at

a small, focal area. The casualty with a significant closed head injury will usually present in

coma, with or without lateralizing signs such as

extraocular motility and pupillary pareses or

asymmetrical posturing. Closed or open facial

injuries may well be present also, and airway

obstruction must always be the first consideration. Injuries to other parts of the body must be

suspected and searched for. Although most casualties with a significant, life-threatening head

injury will be comatose when they are evaluated

initially, a significant number will be awake but

will subsequently deteriorate; a patient with

mental status changes, focal neurological findings (particularly those suggestive of a seizure),

or even a good history for significant head injury

must be observed very carefully.

Casualties with open head injuries may appear more frightening, particularly if brain is

exposed, but as noted above, they may have less

diffuse brain injury than casualties with closed

head injuries. Casualties with open head injuries

(and even exposed and injured brain) may be

wide awake and alert, often with only a minor,

focal, neurological deficit—or no deficit at all.

On the other hand, a wound to the brain made by

a small fragment or a bullet that has not glanced

may well have only a small wound of entrance

with extremely little surface tissue damage. These

wounds are often much more serious than those

involving much more significant surface tissue

damage, mostly because in the latter case, the

kinetic energy imparted to the head at the wound

of entrance is often superficial and tangential. A

computed tomography (CT) scan of the former

type of wound will often disclose significant intracranial injury that was belied by the relatively

benign appearances of the scalp and bone injuries. Such a scan will usually demonstrate significantly greater tissue injury at the wound of

exit, especially when the penetrating missile is a

bullet. The reason for the greater damage at a

bullet’s wound of exit is that yaw and tumbling

are much more prominent here than at the wound

of entrance. For this reason, if the bullet or an

irregular fragment has actually exited through

the side opposite the wound of entrance, or is

lying near the inner surface of the calvarium on

the opposite side, that side should generally be

addressed first at the time of surgery—as soon as

any life-threatening superficial bleeding has been

stopped at the wound of entrance. The technique

will be discussed in greater detail later in this

chapter.

A casualty with a glancing or a relatively shallow

injury will often present with much more extensive

superficial tissue damage. Here the cerebral damage will be relatively superficial and usually not

involve the deeper structures. An example of this

would be two different types of self-inflicted gunshot wounds. In the first instance, the individual

would point the barrel of the gun directly at his

temporal region, then pull the trigger. On leaving

the barrel of the gun, the bullet would enter immediately, pass through both hemispheres, and exit

the calvarium at the other side. In all likelihood, the

greater cerebral damage would be just inside the

wound of exit. The superficial damage at the

wound of entrance would be relatively slight. In

the second instance, consider that the individual

flinched at the last instant, turning the barrel so

that it was nearly parallel to the plane that was

tangential to the skull at the site of the wound.

Here, extensive scalp damage would occur and

the depressed skull fracture would traverse the

the calvarium up to the point where the tangent

plane was no longer in contact with the skull.

The cerebral damage would be limited to the

surface and perhaps a centimeter or so in depth.

Keeping these two examples in mind will allow

the medical officer to interpret the clinical significance of the appearance of different types of

penetrating injury.
Neurological Injuries

379

GOALS OF NEUROSURGICAL INTERVENTION

the clear standard until a reasonable update was

suggested by Benny Brandvold and colleagues8 in

1990, writing of their experiences with casualties

evacuated to Rambam Maimonides Medical Center, Haifa, Israel.

The first priority in any trauma surgery is invariably the control of hemorrhage; the second is the

removal of contaminated material and nonviable

tissue. In this regard, open head injury is no exception and initial hemorrhage control is straightforward. Purely on the basis of cerebral compression,

it is virtually impossible to exsanguinate into the

substance of the brain (unlike into the abdomen or

most other regions of the body). The only exception

is in the newborn, with its large intracranial volume

relative to the rest of its body, and its widely expansive cranial sutures. It is also impossible for hemorrhage deep in the cerebral substance to continually

drain a penetrating wound, as the brain will swell and

shut off such egress very rapidly. All exsanguinating

hemorrhage in open head injury must then emanate

from skin, bone, the dural sinuses, or extremely

superficial cortical vessels. The scalp is well

vascularized, and exsanguination from a scalp laceration alone is possible. Bleeding from the diploic

spaces of fractured calvarium is generally limited to

a moderately brisk ooze, at most, but over time this

can be significant. Unless instantly tamponaded by

a depressed bone fragment, bleeding from a lacerated dural sinus would generally result in

exsanguination after a few minutes. The surgeon

will therefore see this kind of hemorrhage only

after an appropriately situated, depressed fracture is elevated. Brisk bleeding from a cortical

(pial) vessel is often seen on elevation of depressed bone.

The first steps of surgical treatment will therefore be the control of hemorrhage from the sources

described above. Tricks that help the surgeon depend on a familiarity with the anatomy and character of the vessels in each of these areas. Cessation of

scalp bleeding, for example, requires coagulation of

individual vessels that are found immediately deep

to the galea. Grabbing the galea with forceps will

disclose these structures quite easily. Bone hemostasis can readily be obtained by rubbing a small

amount of bone wax over the cut edge. Dural sinus

bleeding will be extremely profuse as soon as the

tamponading bone has been removed, but it can be

slowed down considerably by simply elevating the

head of the table (ie, putting the patient into a

Aside from debridement, treatment modalities

for casualties with head injuries are, for the most

part, nonsurgical. Injury to central nervous system

substance cannot be repaired by any primary

physical intervention (analogous to suturing for

the repair or reanastomosis of a lacerated abdominal organ). If central neural fibers are cut or

definitively crushed, there is no treatment, surgical or otherwise, that will restore function. If, on

the other hand, the substance of central neural

fibers is intact but their function is reversibly

impaired (ie, a situation analogous to that of

neuropraxia in the peripheral nervous system),

certain interventions seem to be capable of altering the physiological environment to make it more

conducive to the reversal of the dysfunction. Consequently, nonsurgical treatment of casualties with

head injuries is emphasized in this chapter, although several surgical considerations require

discussion.

The goal of surgery in closed head injury is generally limited to decompressing the brain parenchyma by removing a mass lesion, which will almost invariably be a hematoma. The only exceptions

to this procedure would be the relatively rare circumstances in which (a) a lobectomy would be

performed to remove edematous brain or (b) a cerebrospinal fluid leak would be repaired. The former

would usually be a delayed procedure, necessitated

at the time of peak swelling (48–72 h after the

injury); the latter would almost invariably be delayed well beyond that time.

In open or penetrating head injury, the goals are

generally very clearly defined; unlike the usual

situation with closed head injury, at least some

degree of surgical treatment is almost invariably

indicated. Perhaps the first truly comprehensive

description of modern neurosurgical techniques in

open head injury can be found in Harvey Cushing’s

106-page article published in 1918 in the British

Journal of Surgery,

5 in which he chronicles his extensive experience obtained on the World War I battlefields of France. This, along with his companion

article published the same year in the British Medical

Journal,

6 set the procedural standards, which remained essentially unchanged (aside from the development of certain new hemostatic techniques)

until the work of Arnold M. Meirowsky,7 published

half a century later in an official history of the U.S.

Army Medical Department, and based on his Korean War experience. Meirowsky’s article remained
Anesthesia and Perioperative Care of the Combat Casualty

380

reverse Trendelenburg’s position). Too much elevation, on the other hand, can allow air to be

entrained into the sinus, which is rigidly supported

by the dura. This can easily lead to an air embolus.

The trick, therefore, is to elevate the head of the bed

just enough to allow a slow egress of blood, which

will permit the surgeon to repair the sinus with

direct suture or a patch of cadaver dura or fascia.

The bony diploë also contain blood-filled spaces

that will entrain air if the head of the bed is high

enough. Rapid and accurate use of wax is extremely

important here. Bleeding from the superficial cortex is generally from vessels immediately deep to

the pia mater, and most of these can be identified

and cauterized.

Once life-threatening hemorrhage has been

controlled, the surgeon’s attention is turned to

debridement of the projectile tract. Contaminated cerebral substance that is oozing out of the

wound site is totally nonviable and will never

regain function. It can therefore be removed

without condemning the patient to further deficit. If left in place, it will undoubtedly lead to

further necrosis, cerebritis, and abscess formation. All devitalized brain tissue must therefore

be removed by suction, which is continued until

the tract remains open and does not immediately

swell shut.

Meirowsky believed that the entire wound tract

absolutely required radical debridement, and that

all foreign material, aside from the metal itself,

required complete removal. For many years, all

bone was searched for, even if it meant increasing

the deficit, as surgeons believed that any retained

bone would unquestionably lead to abscess formation. However, the Vietnam Head Injury Study9 has

suggested that, although careful debridement is

indicated, small amounts of bone left in place

may not lead to quite as dangerous a situation as

Meirowsky had previously suggested. More recently, experience in the the Israeli–Lebanese War

has suggested that with mandatory monitoring a

slightly more conservative approach may be acceptable, as long as the threshold for emergent

intervention remains low.8 Presumably, newer

antibiotics and better imaging techniques have

been instrumental in this change in philosophy

(Figure 16-3).

As Cushing pointed out in 1918, failure to close

(or patch) the dura will lead to the development of

fungus cerebri (ie, an ulcerated cerebral hernia with

granulation protruding from the scalp wound).

Inattention to dural tears at the base of the skull will

lead to cerebrospinal fluid leaks through the nose or

a

Fig. 16-3. This combat casualty has a typical penetrating head wound (made by a preformed fragment from

an improved fragmentation grenade). At the time of

operation, the casualty was alert and able to move his

extremities normally. (a) The casualty before induction of anesthesia. The wound of entrance is seen in

the right frontal region. The radiographs demonstrate

that the fragment (b) has crossed the midline and (c)

has come to rest in the superficial portion of the

casualty’s left parietal cortex. (d) A craniectomy has

been performed and (e) the missile tract at the wound

of entrance has been debrided. (f) The craniectomy

site has been closed with a fascial graft. (g) An

anteroposterior radiograph of the skull shows the large

defect left by the craniectomy. The fragment is still

present. The tissue damage and resulting heightened

neurological defect caused by its removal would probably not have been justified by the resultant decrease

in the risk of complications such as sepsis arising from

a retained foreign body. In contrast to bullets, fragments usually cause more tissue damage where they

enter the brain substance than they cause in the more

distant parts of their pathway. Photographs: Swan

Vietnam Surgical Slide Collection.

ear, which may lead to a need for subsequent surgical repair. Closed head injuries may also require

delayed surgical treatment for cerebrospinal fluid

rhinorrhea or otorrhea.

Once these surgical considerations have been

addressed, the nonsurgical interventions, which can

improve the physiological environment so as to

promote neural survival and recovery (as well as

the survival and recovery of the casualty) may be

entertained. Future surgical considerations will

be limited to unfortunate circumstances such as

delayed brain swelling (rarely requiring lobectomy), further cerebrospinal fluid leaks, or abscess formation.
Neurological Injuries

381

b

e

c

g

d

f
Anesthesia and Perioperative Care of the Combat Casualty

382

PATHOLOGICAL ANATOMY AND PHYSIOLOGY OF TRAUMATIC BRAIN INJURY

Closed Brain Injury

Most forms of acute brain injury in humans result

from sudden cranial impact or angular cranial acceleration. Impact injuries deform and sometimes

fracture the skull, initiating shock waves that are

transmitted throughout the brain. When brain tissue strikes bony intracranial prominences, disruption of vascular integrity may produce focal injuries. The clinical spectrum of anatomical findings

in minor, moderate, and severe diffuse brain injuries has been reproduced experimentally.13 Neurological outcome after experimental head trauma

correlates with the degree of parenchymal brain

injury, especially the extent of primary axonal injury. Traumatic brain injury also alters the cerebral

vasculature and disrupts the blood–brain barrier.

This disruption may represent the most fundamental response of the brain vasculature to injury and

may be a primary mechanism of concussion.14

The systemic physiological responses to experimental brain injury include an immediate period of

apnea, the duration of which increases with increasing severity of injury.15 Hypertension and

bradycardia immediately follow moderate-to-severe injury, even if mechanical ventilation prevents

apnea. Intracranial hypertension consistently accompanies the arterial hypertension; however, intracranial pressure (ICP) returns to normal before

the arterial blood pressure. Intracranial hypertension is usually not sustained after experimental

head injury.

Penetrating Brain Injury

The pathophysiology of experimental penetrating brain injury has been less extensively investigated than closed head injury. The duration of

injury-induced apnea increases in proportion to the

muzzle energy of the projectile. Blood pressure and

cerebral perfusion pressure (CPP) tend to increase

steadily after wounding.16 In monkeys, missile

wounds produce dramatic, immediate increases in

ICP (to 40–60 mm Hg) that persist for at least 10

minutes after impact. As CPP falls to approximately 50% of preinjury levels, cerebral blood flow

(CBF) declines to approximately 60% of baseline.17

Enhanced Vulnerability to Secondary Ischemic

Brain Injury

Current clinical and experimental data leave little

doubt that the traumatized brain is uniquely vulTraumatic brain injuries are diffuse or focal.

Comatose trauma patients who demonstrate no focal lesions by CT or magnetic resonance imaging

(MRI) during initial diagnostic assessment are said

to have diffuse brain injury. Diffuse injury includes

diffuse axonal injury, hypoxic brain injury, diffuse

brain swelling, and diffuse punctuate brain hemorrhages; focal brain injury includes contusions, avulsions, hematomas, hemorrhages, infarctions, and

infections. Diffuse injuries produce coma through

damage to the brainstem or cerebral cortex. Focal

injuries produce coma by brain compression, brain

shift, or herniation. Patients with diffuse brain

injury are much less likely than those with focal

injuries to have sustained a skull fracture or cerebral contusion, to develop signs of sustained intracranial hypertension, or to have a lucid interval after

injury before becoming comatose.2

Hypoxic cerebral damage, a common postmortem finding after blunt head trauma,10,11 is associated with arterial hypoxemia or cerebral hypoperfusion, occurring as a consequence of shock,

sustained intracranial hypertension, or cerebral

vasospasm.

Both cerebral edema and cerebral swelling occur

after brain trauma. Vasogenic cerebral edema results when damage to the blood–brain barrier leads

to increased accumulation of interstitial water.

Cytotoxic edema, characterized by cellular water

accumulation, may follow cerebral hypoxia. In

contrast, diffuse cerebral swelling represents vascular congestion, evident on CT scan as symmetrical effacement of the lateral ventricles and

the basal cisterns, and normal or increased white

matter density.

Ten percent of patients with closed head injuries

and Glasgow coma scale (GCS) scores of 13 will

require surgery for intracranial lesions. This decision, will, of course, be made on a combination of

clinical and radiographic (ie, CT) criteria. The most

common focal injuries are cerebral contusions,

intraaxial (within the substance of the neuraxis)

hematomas, and extraaxial (subdural and epidural)

hematomas. Extraaxial hematomas are rarely detected in patients who have both a GCS score of 15

and no focal neurological deficits.12 On CT,

subdural hematomas tend to be crescent shaped,

spreading out across the brain surface. In contrast, the typical epidural hematoma has a biconvex (ie, lens-shaped) appearance. Delayed intracerebral hematomas may follow a combined

traumatic and anoxic insult.
Neurological Injuries

383

nerable to posttraumatic ischemic insults. Disability and death arising from insults such as

hypotension and hypoxemia are important because

they occur after patients have entered the medical

care system. Consequently, prevention and effective treatment of secondary ischemic insults should

limit morbidity and mortality.

Secondary ischemic brain injury appears to contribute to poor outcome after traumatic brain injury. In one study,11 nearly 90% of patients who

died after traumatic brain injury showed ischemic

lesions in a variety of patterns. Diffuse ischemic

injury was evident in 23.5%, arterial boundaryzone ischemic injury in 7.5%, ischemia in a specific

arterial territory in 10.5%, and hippocampal ischemic

injury in 45%.

Hypotension and hypoxemia—systemic insults

that can induce cerebral hypoperfusion—worsen

outcome, both in terms of higher mortality and

worse neurological recovery, after head injury. In

1981, researchers2 examined the effects of a variety

of potential secondary insults on the incidence of

unfavorable outcome (ie, severe disability, persistent vegetative state, or death) after severe traumatic brain injury and found that a systolic blood

pressure of 90 mm Hg or lower on admission to the

hospital was associated with an increase in the

incidence of unfavorable outcomes, from 35% to

65%; and hypoxemia (≤ 60 mm Hg on admission)

was associated with an increase in unfavorable outcomes, from 35% to 59%. A retrospective review

published in 19931 of the experience of the Trauma

Coma Data Bank even more strongly suggests that

hypotension is a powerful predictor of poor outcome after head injury.

Experimental brain injury is followed by a decrease in brain pH and, under certain circumstances,

both a decline in high-energy phosphate compounds

and an increase in tissue lactate levels. Posttraumatic deterioration in cerebral aerobic metabolism

is aggravated by concurrent hypoxia or hypotension.

After experimental injury, severe hypoxemia (PaO2

< 40 mm Hg) worsens neurological deficits and

brain ischemia, increases tissue inorganic phosphate,

and reduces phosphocreatine and adenosine triphosphate.18 Similarly, hypotension that alone would

not alter the cerebral energy state (assessed by magnetic resonance spectroscopy) reduces brain intracellular pH, adenosine triphosphate, and phosphocreatine, and increases the concentration of inorganic

phosphate after brain trauma.19 On the other hand,

a study with animals published in 199320 demonstrates the existence of an impact level beyond which

the head-injured subject never fully recovers from

the initial postinjury drop in blood pressure. The

deterioration of brain metabolism that follows the

combination of hypoxemia or hypotension with

experimental brain injury underscores the necessity for prompt restoration of oxygenation, perfusion pressure, and ventilation in patients with head

injuries.

Traumatic brain injury initiates a variety of additional biochemical changes, each of which could

contribute to enhanced vulnerability to subsequent

vascular or tissue injury. Free oxygen radicals may

interfere with the normal ability of the cerebral

vasculature to dilate in response to declining blood

pressure.21 In cats subjected to head injury, hemorrhagic hypotension reduces CBF more than in control animals.22,23 Compensatory cerebral vasodilation also fails to occur in response to hemodilutional

resuscitation after hemorrhage and head trauma.24

Increases in excitatory amino acids such as

glutamate and aspartate, which activate N-methylD-aspartate (NMDA) receptors (among others), correlate with the severity of brain injury in rats and

with reduced availability of high-energy phosphate

compounds.25 Evidence also suggests that cholinergic mechanisms mediate enhanced vulnerability

to global cerebral ischemia after experimental head

injury.26 The metabolism of cell membrane lipids

generates prostaglandins, leukotrienes, and oxygen free radicals. The presence of extravascular

blood also generates free radicals. Experimental

brain injury increases thromboxane A2, a powerful

vasoconstrictor and platelet aggregator, and also

increases brain levels of prostaglandin E2, a compound that has been associated with reduced motor

activity.27 Finally, some classes of endogenous and

exogenous opioid agonists and antagonists may

aggravate, while others may limit, brain injury. For

example, naloxone, a nonspecific opiate antagonist,

significantly worsens outcome after fluid-percussion head injury in rats, whereas morphine reduces

deficits.28

Although preadmission hypotension and hypoxemia are associated with worse outcome, such insults continue to occur after admission to the hospital, raising the possibility of limiting secondary

ischemic injury, either through effective prevention

or through preischemic pharmacological intervention. Among a series of 100 patients in an intensive

care unit after mild, moderate, or severe traumatic

brain injury, hypotension (mean arterial pressure

[MAP] ≤ 70 mm Hg) occurred in 76%; reduced CPP

(≤ 60 mm Hg), defined as MAP minus ICP, occurred

in 78%; and hypoxemia (≤ 90% hemoglobin saturation) occurred in 43%.29 In eight patients who un-
Anesthesia and Perioperative Care of the Combat Casualty

384

derwent ICP monitoring after severe traumatic brain

injury without evidence on cranial CT of intracranial hypertension, ICP exceeded 20 mm Hg for

more than 5 minutes in seven patients, and CPP was

less than 60 mm Hg for more than 5 minutes in five

patients.30 Therefore, systemic insults that could

worsen outcome by inducing cerebral ischemia occur commonly in patients with head injuries, both

at the time of admission to the hospital and during

intensive care.

To further support the likelihood that postadmission cerebral ischemia contributes to poor outcome

after traumatic brain injury, patients who survived

head injury demonstrated evidence of ischemic injury on CT. In 1987, researchers31 monitored the

cerebral metabolic rate for oxygen (CMRO2) and the

cerebral metabolic rate for lactate in 44 patients

with severe head injuries, and correlated those results with changes in cranial CT scans. Although 27

patients developed low-density areas surrounding

intracranial hematomas, 6 others developed evidence of cerebral infarction not associated with

hematomas. Low CMRO2 and net cerebral lactate

production were found to be weak predictors of

later infarction.

Recognition (via continuous monitoring) of cerebral ischemia during intensive care offers the possibility of prompt intervention. Several investigators

have examined the ability of jugular venous bulb

monitoring to detect ischemia. The jugular venous

bulb provides “mixed” cerebral venous blood, relatively uncontaminated by extracranial venous effluent. Like mixed systemic venous sampling, cerebral venous oxygenation provides information that

suggests but does not prove cerebral ischemia. In 45

patients cared for in intensive care units after traumatic brain injury, 33 episodes of jugular desaturation below 50% were documented.32 One researcher33

reported 121 episodes of combined arterial and

jugular venous desaturation during intensive monitoring of 69 patients with severe head injuries; of

the 121 episodes, 32 (26.5%) responded poorly to

treatment. Prolonged desaturation was associated

with deterioration of the GCS score.33 More importantly, among 102 patients with GCS scores below 9

on admission or on the first day thereafter, one

episode of jugular venous desaturation (< 50%

for > 10 min) was associated with good recovery

or moderate disability in 23%, more than one

episode with good recovery or moderate disability in 12%, and the absence of jugular venous

desaturation with good recovery or moderate

disability in 46%.34

Systemic and Organ-System Responses

Clinical head injury is associated with sympathetically mediated hypertension, tachycardia, and

increased cardiac output. The more severe the level

of isolated clinical head injury (ie, the lower the

GCS score), the greater the increase in plasma norepinephrine levels and heart rate.35 However, experimental data20 suggest that beyond a threshold

impact level, the increase in catecholamines no

longer linearly correlates with the intensity of the

impact. In sympathetically stimulated patients with

head injuries, β-adrenergic blockade reduces heart

rate, cardiac index, and circulating catecholamines.36

In addition to the characteristic hyperdynamic

response associated with head injury, hypertension

also accompanies severe increases in ICP, a response first recognized by Cushing in 190337 and

now known as the Cushing phenomenon. If permitted to progress and depending on the direction in

which the brain expands, increasing intracranial

hypertension may produce medullary compression

and precipitous systemic hypotension. Management of the Cushing phenomenon consists of therapy to reduce ICP, thereby interrupting the reflex

response. If systemic hypertension is secondary to

the Cushing phenomenon, attempts to control blood

pressure using vasodilators may both reduce MAP

and increase ICP, thereby further compromising

cerebral perfusion.

Patients with head injuries also undergo stressinduced hyperglycemia and accelerated protein

wasting. The frequent occurrence of fever and

hypoalbuminemia has been attributed to endothelial cell injury.38

Pulmonary Effects

Acute head injury is associated with a variety of

respiratory problems, some potentially fatal (eg,

apnea, central neurogenic pulmonary edema, and

altered breathing patterns), as a result of associated

injuries, fat embolism syndrome, pulmonary contusion, and hemopneumothorax. Hypoxemia may

occur even in patients who lack auscultatory or

radiographic evidence of pulmonary compromise,

apparently because of failure of mechanisms that

regulate ventilation–perfusion matching.39 Central

neurogenic pulmonary edema, a rare, acutely lifethreatening complication usually seen accompanying severe injury, may result from acute left atrial

hypertension or increased pulmonary capillary permeability.40 Management of central neurogenic
Neurological Injuries

385

pulmonary edema necessitates prompt correction

of intracranial hypertension, if present, in addition

to therapy to improve oxygenation.

Coagulopathy

Laboratory evidence of disseminated intravascular coagulation is reported in nearly one fourth of

patients with head injuries.41 Patients with higher

concentrations of fibrin degradation products have

poorer functional outcomes and are more likely to

develop the adult respiratory distress syndrome.42

Cerebral Circulatory Responses

Acute head injury of sufficient severity to produce coma is associated with moderately decreased

CBF, markedly depressed CMRO2, and highly variable autoregulation and carbon dioxide reactivity.

The uninjured cerebral circulation is responsive to

changes in metabolic demand; CPP; the partial pressure of carbon dioxide, arterial (PaCO2); and the

partial pressure of oxygen, arterial (PaO2). Cerebral

blood flow normally is coupled to CMRO2, which

varies directly with body temperature and the level

of brain activation; that is, CMRO2 is increased by

fever, seizures, or pain. Cerebral blood flow remains constant (approximately 50 mL/100 g/min

in adults) in the normal brain as CPP changes over

a range of approximately 50 to approximately 130

mm Hg. In normal individuals, over a range of

PaCO2 from 20 to 80 mm Hg, CBF will be acutely

halved if PaCO2 is halved and will double if PaCO2 is

doubled. That relationship is apparently intact in

most patients with head injuries. PaO2 exerts little

effect on CBF unless PaO2 declines below 60 mm Hg

(hemoglobin saturation < 90%). Below that level,

CBF increases abruptly.

In 1991, one group of researchers43 reported that

CBF was less than a critical value of 18 mL/100 g/

min in one third of measurements made within 6

hours of injury in 106 patients with head injuries.

Moreover, the average difference in cerebral arteriovenous oxygen content (AVDO2) was greater than

normal during this critical early interval (Figure 16-

4), suggesting that CBF was indeed inadequate.43

Later, in the days after injury, some patients with

head injury demonstrate depressed levels of both

CMRO2 and CBF, while others demonstrate uncoupling, with CBF substantially in excess of CMRO2

(Figure 16-5).44 Nearly 90% of patients younger

than 18 years of age demonstrate relative cerebral

hyperemia, defined as CBF that exceeds metabolic

demand, or even exceeds normal values, at some

point during intensive monitoring.45

Experimental and clinical data46 demonstrate that

CBF after head trauma frequently is MAP dependent rather than MAP independent (Figure 16-6).

Most patients with mass lesions demonstrate defective autoregulation; conversely, autoregulation remains intact in many patients without intracranial

mass lesions.46 In patients with head injuries in

whom autoregulation is intact, mannitol reduces

ICP and does not change CBF; if autoregulation is

defective, ICP changes little and CBF increases.47

In many patients, reduced CBF appears to represent appropriate coupling between low CMRO2 and

low CBF rather than cerebral ischemia.44 However,

patients with low but coupled CBF may be vulnerable to excessive vasoconstriction during acute hyperventilation. Nearly 20% of patients develop a

wide cerebral AVDO2 during hyperventilation, sugFig. 16-4. Time course of mean arteriovenous oxygen

difference (AVDO2) in patients with head injuries and

with motor scores of 1 or 2, and those with motor scores

of 3 to 5 (motor score is measured as the best response

to a painful stimulus: 1 = no response; 2 = extension;

3 = abnormal flexion; 4 = flexion withdrawal; 5 = localizing response). Error bars represent the standard error of

the mean. Reprinted with permission from Bouma

GJ, Muizelaar JP, Choi SC, Newlon PG, Young HF. Cerebral circulation and metabolism after severe traumatic

brain injury: The elusive role of ischemia. J Neurosurg.

1991;75:688. AVDO2 (mL/100mL)

9.0

8.0

7.0

6.0

5.0

4.0

3.0

< 8 8–12 12–24 24–28 > 48

Hours After Injury

Motor Score

= 1,2

= 3,4,5
Anesthesia and Perioperative Care of the Combat Casualty

386

x = Hyperemia

• = Reduced Flow

Fig. 16-5. In patients who have sustained closed head injury, both the cerebral metabolic rate of oxygen consumption (CMRO2, the abscissa) and cerebral blood flow (CBF,

based on 133Xe clearance integrated over 15 min, the ordinate) are reduced. (Normal values are 3.4 mL/100 g/min

and 50 mL/100 g/min, respectively). In some patients

(closed circles), CMRO2 and CBF appear to be reduced to a

similar extent (ie, coupled). In others (represented by the

x’s), global CBF is higher than apparently is necessary to

meet metabolic demand (uncoupled). Reprinted with permission from Obrist WD, Langfitt TW, Jaggi JL, Cruz J,

Gennarelli TA. Cerebral blood flow and metabolism in

comatose patients with acute head injury: Relationship to

intracranial hypertension. J Neurosurg. 1984;61;247.

gesting that hyperventilation therapy occasionally

may adversely influence cerebral perfusion

(Table 16-1).44 If increased ICP develops in patients

with a wide cerebral AVDO2, other measures to

reduce ICP, such as sedation or osmotic diuresis,

produce better matching of cerebral oxygen supply and demand than further hyperventilation.

If CBF measurements are unavailable, the calculation of the cerebral oxygen extraction or the

lactate extraction may provide clinically useful

information regarding the adequacy of cerebral

oxygen delivery.31–33,48–50

0 25 50 75 100 125 150 175

75

60

45

30

15

Cerebral Blood Flow (mL/100 g/min)

0

Mean Arterial Pressure (mm Hg)

Fig. 16-6. In comparison to the normal autoregulatory

curve (open circles), adult patients who have sustained

closed head injury have reduced flow, and in some cases

(closed triangles), impaired autoregulation. Other patients have reduced flow and preserved autoregulation

(open triangles). Data source: Muizelaar JP, Lutz HA III,

Becker DP. Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely headinjured patients. J Neurosurg. 1984;61:700–706.

TABLE 16-1

FINDINGS IN 10 PATIENTS WITH WIDE ARTERIOVENOUS OXYGEN DIFFERENCES

AFTER HEAD INJURY*

Hemodynamic Hyperventilated Normal Value

Variable Patients* (PaCO2 ≈ 40 mm Hg)

CMRO2 1.9 ± 0.5 3.3 ± 0.4

CBF15 18.6 ± 4.4 53.3 ± 6.8

AVDO2 10.5 ± 0.7 6.3 ± 1.2

VPO2 22.3 ± 1.8 37.5 ± 5.6

*Values are means ± standard deviations obtained 10 to 85 h after the injury

AVDO2: arteriovenous oxygen differences (in vol %); CBF15: mean cerebral blood flow based on 133Xe clearance integrated over 15

min; CMRO2: cerebral metabolic rate for oxygen (in mL/100 g/min); VPO2: jugular venous oxygen tension (in mm Hg)

Reprinted with permission from Obrist WD, Langfitt TW, Jaggi JL, Cruz J, Gennarelli TA. Cerebral blood flow and metabolism in

comatose patients with acute head injury: Relationship to intracranial hypertension. J Neurosurg. 1984;61:251.

60

50

40

30

20

10

CBF15

0.5 1.0 1.5 2.0 2.5 3.0

CMRO2
Neurological Injuries

387

CARE OF THE PATIENT WITH TRAUMATIC BRAIN INJURY

Initial Care

Two assessment systems can be used to understand the reports that characterize the initial management of traumatic brain injury. The first, the

GCS, was originally developed to permit comparisons among series of patients with traumatic brain

injuries, based on their initial clinical presentation

(Table 16-2).51 Consisting of three major categories

(eye opening [1–4 points], verbal responses [1–5

points], and motor function [1–6 points, assessed

in the best responding limb]), the GCS score

ranges from 3 to 15. Mild head injury is defined

as scores ranging from 13 to 15, moderate as scores

from 9 to 12, and severe as 8 or less. The GCS

constitutes a reliable index of overall brain function with minimal interobserver variability. The

second system, the Glasgow outcome scale (GOS)

defines five categories: good recovery, moderate

TABLE 16-2

GLASGOW COMA SCORE

Component Response Score

Eye Opening Spontaneously 4

To verbal command 3

To pain 2

None 1

Subtotal (1–4)

Motor Response Obeys verbal command 6

(best extremity) Localizes pain 5

Flexion-withdrawal 4

Flexion (decortication) 3

Extension (decerebration) 2

No response (flaccid) 1

Subtotal (1–6)

Best Verbal Response Oriented and converses 5

Disoriented and converses 4

Inappropriate words 3

Incomprehensible sounds 2

No verbal response 1

Subtotal (1–5)

Total (3–15)

Reprinted with permission from Teasdale G, Jennett B. Assessment of coma and impaired consciousness. Lancet. 1974;2:81–84.

TABLE 16-3

GLASGOW OUTCOME SCALE

Patient Outcome Description

Good Recovery Normal or minimally impaired

patients who have returned

to school, university, or

former occupation, or are

capable of managing their

households

Moderate Disability Patients who can perform the

tasks of daily living but are

no longer able to work or

attend school

Severe Disability Patients who require assistance to perform the tasks of

daily living but do not

require institutional care

Persistent Vegetative Patients remain unresponsive

State and speechless for weeks or

months; absent function in

the cerebral cortex (as judged

behaviorally) although cortex

may appear structurally

intact

Death Patients do not regain consciousness; most deaths occur

within 48 h

Reprinted with permission from Jennett B, Bond M. Assessment

of outcome after severe brain damage: A practical scale. Lancet.

1975;1:480–484.

disability, severe disability, persistent vegetative state, and death (Table 16-3).52 Defined in

these terms, about 2,000 to 3,000 patients per

million population per year come to medical attention; 85% to 90% are in the mild category, 5%

to 10% in the moderate, and 5% in the severe.29

The GCS is a powerful predictor of the final

outcome (Table 16-4).53

Prompt application of basic life support may

prevent secondary hypoxic brain damage.54 Secondary insults such as anemia, hypotension, hypoxemia, and hypercarbia, alone or in combination,

occur in nearly 50% of comatose patients with head

injuries (Table 16-5).2 Thus, tracheal intubation,

positive-pressure ventilation with oxygen, and systemic hemodynamic resuscitation should be initiated promptly when indicated, and should not be
Anesthesia and Perioperative Care of the Combat Casualty

388

GCS Score GCS Score GCS Score Total

3–4 5–6 7–9 Cases

TABLE 16-4

RELATION OF ACUTE GLASGOW COMA SCALE SCORE TO GLASGOW OUTCOME SCALE SCORE*

TABLE 16-5

INFLUENCE OF REMEDIABLE CAUSES OF SECONDARY INJURY ON OUTCOME

AFTER HEAD INJURY

deferred until the patient arrives at a trauma

center.

Intubation of patients with head injuries, who

also may have unrecognized cervical spine injuries,

presents a challenge in which several therapeutic

conflicts must be balanced. Inadequate ventilation

and oxygenation must be promptly reversed. Ideally, profound sedation and muscle relaxation limit

increases in ICP associated with endotracheal

intubation; however, hypovolemia resulting from

associated injuries may contraindicate effective sedation. Intubation may be technically difficult owing

to trauma to facial structures or to trismus. In such

cases (and if time permits), it may be practical to

secure an airway using a fiberoptic endoscope.

Occasionally, cricothyroidotomy, transcricothyroid

oxygen insufflation, or formal tracheostomy may

be required. Facial fractures constitute a relative

contraindication to nasotracheal intubation.55

Despite legitimate concern that the depolarizing

muscle relaxant succinylcholine may increase ICP,56

its more rapid onset of action, compared with that

of nondepolarizing muscle relaxants, may make it

necessary to use succinylcholine for immediate

intubation of an unstable patient. After intubation,

the patient should be ventilated with an oxygenGOS Score No. (%) of Cases

Dead/PVS 15 (78.9%) 19 (45.2%) 9 (25.7%) 43

SD/MD/GR 4 (21.2%) 23 (54.8%) 26 (74.3%) 53

Total Cases 19 42 35 96

*Significance: P < .0001 (chi-square)

GCS: Glascow Coma Scale; GOS: Glasgow Outcome Scale; PVS: persistent vegetative state; SD: severe disability; MD: moderate

disability; GR: good recovery

Reprinted with permission from Jaggi JL, Obrist WD, Gennarelli TA, Langfitt TW. Relationship of early cerebral blood flow and

metabolism to outcome in acute head injury. J Neurosurg. 1990;72:178.

Poor Outcome*

Secondary Insult Definition (%)

Hypoxemia PaO2 < 60 mm Hg 59

Hypotension SBP < 90 mm Hg 65

Anemia Hct < 30% 62

Hypercarbia PaCO2 > 45 mm Hg 78

Intracranial hypertension ICP > 20, reducible 45

ICP > 20, not reducible 95

*Poor outcome: severe disability, persistent vegetative state, or death

Hct: hematocrit; ICP: intracranial pressure; SBP: systolic blood pressure

Adapted with permission from Miller JD, Butterworth JF, Gudeman SK, et al. Further experience in the management of severe head

injury. J Neurosurg. 1981;54:292.
Neurological Injuries

389

Shock

After Resuscitation

*P < 0.05 SAL vs HS, Group I

**P < 0.001 SAL vs HS, Group II

BL T15 T35 T95 T155

40

30

20

10

0

-10

Time (min)

Intracranial Pressure (mm Hg)

Group I Group II

HS HS

SAL SAL

Fig. 16-7. Response of intracranial pressure (ICP) to resuscitation from shock with 7.2% hypertonic saline (HS) or 0.8%

saline (SAL) in animals without (Group 1) and with (Group 2) a right hemispheric intracranial mass. Intracranial

hypertension (15 mm Hg) in Group 2 was induced by inflation of a right-hemispheric subdural balloon to which

additional saline was added as necessary to maintain ICP at 15 mm Hg during shock. Shock extended from 0 time to

T30 (30 min after initiation of shock). BL denotes baseline; T15 refers to 15 min after the beginning of a 30-min shock

interval; T35, T95, and T155 refer to 5, 60, and 120 min after a single-bolus resuscitation. After a 30-min interval of

hemorrhagic shock at a mean cerebral perfusion pressure of 35 mm Hg, rapid resuscitation consisted of 0.8% SAL (54

mL/kg) or 7.2% HS (6.0 mL/kg). In animals both with and without intracranial mass lesions, ICP was significantly

greater immediately after resuscitation in animals resuscitated with 0.8% SAL than in those resuscitated with 7.2% HS;

differences quickly became statistically insignificant. Reprinted with permission from Prough DS, Whitley JW, Taylor

CL, Deal DD, DeWitt DS. Regional cerebral blood flow following resuscitation from hemorrhagic shock with

hypertonic saline: Influence of a subdural mass. Anesthesiology. 1991;75:323.

enriched gas mixture. Minute ventilation should be

adjusted to maintain PaCO2 at or below 40 mm Hg

unless clinical evaluation or monitoring indicates

severe, acute, intracranial hypertension. Routine

hyperventilation may not improve outcome and

may even be deleterious.57

No resuscitation fluid has proven ideal in patients with multiple trauma and head injury. Several studies with animals have demonstrated lower

ICP or higher CBF when hypertonic saline solutions

are substituted for isotonic fluids (Figure 16-7).58,59

Clearly, hypotonic solutions, which increase brain

tissue volume, should be avoided. The role of

colloid-containing solutions is controversial. Although for years clinicians have considered colloids less likely to increase ICP after head injury,

data suggest that changes in colloid osmotic pressure exert minimal effects on brain water or ICP in

animals both with and without intracranial pathology.60,61 Although rapid resuscitation with 6.0%

hydroxyethyl starch increases ICP less than hemodynamically comparable resuscitation using lactated Ringer’s solution,62 the difference is probably

due to the fact that lactated Ringer’s solution is

slightly hypotonic.

The neurological examination, preferably conducted before induction of neuromuscular paralysis, should assign a GCS score and, in all comatose

patients, assess brainstem function, (ie, pupillary

light responses and oculocephalic or vestibuloocular

reflexes). Patients should undergo a more complete

neurological examination as time permits, but as

expeditiously as possible. Changes in the examination may be localizing and may dictate intervention, even if they do not change the GCS score.

Clearly, the highest priority for comatose patients with head injuries is to determine the need for

craniotomy. Patients with open or penetrating inju-
Anesthesia and Perioperative Care of the Combat Casualty

390

ries require prompt surgical debridement or, if local

facilities are limited and the patient is sufficiently

stable to transport, transfer to a secondary- or tertiary-care facility. All patients who do not obey

simple commands (in the absence of drug or alcohol

intoxication) require prompt CT scanning to exclude intracranial mass lesions. Patients who require evacuation of subdural hematomas but whose

craniotomy is delayed have a far worse outcome

than those patients whose hematomas are promptly

evacuated.63 Before the widespread availability of

CT and MRI, neuroradiological evaluation could

rapidly be accomplished through either cerebral

angiography or air ventriculography. These latter

two techniques, now rarely used, should be considered if immediate scanning is unavailable, as may

well be true under battlefield conditions. In such

circumstances, a single-shot arteriogram, performed

on initial evaluation of a patient with a high likelihood of an intracranial mass lesion, could be lifesaving. The use of near-infrared spectroscopy to

diagnose acute intracranial hematomas is yet to be

completely evaluated, although preliminary data64

are encouraging.

Adult patients who have briefly lost consciousness, but who subsequently have a completely normal neurological examination, probably do not need

a CT scan in the absence of other clinical indications. The management of patients who have intermediate levels of injury requires repeated evaluation and careful observation.

Diagnostic priorities for other organ systems

should proceed as indicated by the description of

the traumatic event and by the general physical

examination. In all comatose patients with head

injuries, unless they are known to have suffered

only an isolated head injury, abdominal CT scan or

diagnostic peritoneal lavage65 should be performed

to detect occult intraabdominal injury. Patients

should be considered to have cervical spine fractures until this possibility has been excluded by a

cross-table lateral neck radiograph (or a cervical CT

scan) that adequately shows all cervical vertebrae.

Some degree of immobilization (eg, using a hard

collar) should be maintained until the patient is

sufficiently cooperative to perform his own neck

manipulation for flexion and extension films.

Although shock sometimes occurs in association

with an isolated head injury, other causes of

hypotension that must be excluded65 include intraabdominal hemorrhage (evaluated by CT scan or

diagnostic peritoneal lavage), intrathoracic hemorrhage (evaluated by chest radiography, CT scan, or

aortography), long-bone fractures (assessed using a

skeletal survey), myocardial ischemia or cardiac

decompensation (evaluated using electrocardiography or pulmonary arterial catheterization), and

pericardial tamponade (suggested by a paradoxical

pulse, central venous or pulmonary artery pressure

monitoring, chest radiography, echocardiography,

or pericardiocentesis). Untreated shock portends a

worse prognosis.1

Anesthetic Management

Military trauma anesthesia personnel may be

confronted with a spectrum of casualties with head

injuries, from those who arrive from the battlefield

only moments after injury to those who have been

thoroughly evaluated and stabilized. The patient

may be intubated, sedated, and paralyzed, or may

be awake but combative. Surgery may be required

for emergent evacuation of an intracranial hematoma

or may be directed at treatment of injuries to other

organ systems. Therefore, it is obvious that anesthesia personnel participate in a continuum of care

that includes the considerations discussed elsewhere

in this chapter. However, for purposes of brevity,

this section will address questions of anesthetic

management as they apply to unintubated patients

presenting for surgery with moderate-to-severe

head injuries.

Preoperatively, little time may be available for

evaluation. Therefore, the following assumptions

are appropriate. Airway obstruction, hypoventilation, and hypoxia are likely, and oxygen requirements are increased. Both depression of consciousness and injury increase the risk of aspiration of

stomach contents. Hypotension, uncommon in a

patient with an isolated head injury, implies hemorrhage from associated injuries or spinal cord injury

and markedly increases the risk of secondary cerebral ischemia in patients with head injuries. Many

patients with head injuries are hypertensive because of catecholamine release. Some patients are

hypertensive because of physiological reflexes that

attempt to maintain CPP as ICP increases. Only

severe hypertension necessitates treatment; reflex

hypertension caused by intracranial hypertension

requires treatment of increased ICP. Direct vasodilators (ie, nitroglycerine, nitroprusside, and hydralazine) increase CBF and ICP. β-Adrenergic blocking

agents such as esmolol or propranolol or mixed αand β-adrenergic blocking agents such as labetalol

minimally affect ICP.

Monitoring should be determined by the severity

of the injuries and the availability of technologically sophisticated equipment. Resuscitation and
Neurological Injuries

391

stabilization should not be delayed in an effort to

establish better monitoring. If time and circumstances permit, direct arterial pressure monitoring

and central venous pressure monitoring are valuable. Pulse oximetry and capnography provide

early warning of deterioration in gas exchange.

Automated, noninvasive blood pressure monitoring may free anesthesia personnel for other activities. If practical, ICP monitoring may be useful if a

patient with severe head injuries requires extensive

surgery for other injuries.

Volume resuscitation should not be constrained

by fears of increasing cerebral edema. At the present

time, the most appropriate fluid for the initial treatment of hemorrhagic shock in a patient with head

injuries is 0.9% saline, a slightly hypertonic solution

that should result in no increase in brain water or

ICP in areas of brain in which the blood–brain

barrier is intact. Blood products should be given

as indicated and available. More highly hypertonic solutions, which decrease brain water and

ICP in experimental animals and decrease ICP in

humans, may become the treatment of choice in

the future.

Anesthetic induction must preserve CPP. Avoidance of hypotension is more important than reduction of small increases in ICP. Potential induction

agents include thiopental, etomidate, benzodiazepines, and ketamine. Barbiturates decrease CMRO2,

reduce CBF, and reduce ICP. However, large dosages of barbiturates may reduce blood pressure,

especially in hypovolemic patients, and may slow

emergence from general anesthesia. Etomidate provides prompt induction and is usually well tolerated even in moderately hypovolemic patients.

Benzodiazepines decrease CMRO2 and CBF, and

usually preserve blood pressure. Large dosages

may slow emergence. Ketamine, which increases

CBF and ICP, would rarely be appropriate in a

patient with head injuries. Cricoid pressure should

be applied during induction and intubation.

In a patient who is hemodynamically resuscitated, a reasonable sequence is to administer succinylcholine (or a large dose of a nondepolarizing

agent), thiopental, and fentanyl while maintaining

cricoid pressure. In a severely hypovolemic patient, succinylcholine and a small dose of a narcotic or intravenous lidocaine to blunt the hemodynamic response to intubation would be

preferable. Although succinylcholine may increase ICP, expeditious control of the airway is

more important.

Volatile anesthetics decrease CMRO2, but they

also increase CBF and should only be administered

to patients at risk of intracranial hypertension after

hyperventilation has been established. Isoflurane

appears to be most satisfactory. Although nitrous

oxide causes small increases in CBF and CMRO2, the

reduced fraction of inspired oxygen (FIO2) necessitated by nitrous oxide administration limits its use

in patients with lung injury.

Management in the Intensive Care Unit

The primary goals of management in the intensive care unit are to prevent secondary neurological

injury and to limit complications that develop in

other organ systems.

Cerebral Circulatory Considerations

Much of the management of casualties with acute

head injuries is intended to maintain adequate cerebral perfusion. Because CBF is not routinely measured, most cerebral circulatory information is inferred from measurements of PaCO2, blood pressure,

and ICP. Measurement of ICP, combined with

measurement of MAP, permits calculation of CPP

according to the equation:

CPP = MAP – ICP

Cerebral ischemia, defined as inadequate cerebral oxygen delivery (CDO2), can result from a critical reduction of any of the components, including

CBF, hemoglobin concentration, and arterial hemoglobin saturation (SaO2). Uniquely susceptible to

oxygen deprivation, the brain constitutes only approximately 2% of total body weight, but it receives

15% of the cardiac output and accounts for 15% to

20% of total oxygen consumption.

Brain Monitoring

Most global cerebral insults, occurring secondary to hypotension, hypoxemia, or cardiac arrest,

are readily detected by systemic monitors. Therefore, brain-specific monitors can provide additional

information primarily in situations such as cerebral

trauma, in which regional cerebral oxygenation may

be impaired despite adequate systemic oxygenation

and perfusion.

Monitoring devices facilitate early recognition of

physiological derangements that would produce

complications unless effective treatment were provided. The application of brain-monitoring devices

in patients with head injuries therefore presupposes certain assumptions:
Anesthesia and Perioperative Care of the Combat Casualty

392

1. Reduced CDO2 (CBF • arterial O2 content)

is associated with avoidable neurological

morbidity.

2. The proportion of patients who will develop avoidable injury is sufficiently large

to justify extensive application of brainmonitoring devices.

3. Thresholds for intervention can be defined based on experimental and clinical

evidence.

Brain monitors assess, directly or indirectly, cerebral function, cerebral perfusion, or brain metabolism (Exhibit 16-1). The role of brain monitoring has

been incompletely defined in acute head injury.

Many brain monitors, such as those that record

CBF, evoked potentials, and computer-processed

electroencephalograms, are technically challenging

and difficult to apply in combat situations unless

specifically trained personnel are available. More

importantly, no generally accepted protocols have

been developed that establish clinically important

thresholds for monitored variables other than ICP,

define appropriate interventions to improve the

monitored variables, and have been proven to improve outcome.

Operational Characteristics of Monitors

Thresholds of CBF that correlate with various

clinical outcomes, physiological changes, and

changes in monitored variables have been defined

(Table 16-6). It is impossible to predict with certainty if even severe changes in function will be

followed by further cerebral damage. Moreover,

because various brain regions are selectively vulTABLE 16-6

CLINICAL, PATHOPHYSIOLOGICAL, AND MONITORING THRESHOLDS IN CEREBRAL ISCHEMIA

Cerebral Blood Flow Clinical Pathophysiological Electrophysiological

(mL/100 g/min) Findings Changes Changes

50 Normal

23 Reversible paralysis EEG slowing, EP change

20 Na+/K+ pump dysfunction

18 Permanent paralysis EEG flat

15 EP absent

10 K+ efflux, Ca++ influx

EEG: electroencephalogram; EP: evoked potentials

EXHIBIT 16-1

TYPES OF CEREBRAL MONITORING

Function

Evoked potentials

Electroencephalogram

Raw

Processed

Perfusion

Cerebral blood flow

Velocity

Intracranial pressure

Metabolism

Oxygen extraction

Jugular bulb saturation

Near-infrared spectroscopy

nerable to injury, regional ischemia and infarction

may develop without producing changes in monitored variables. The complexity and heterogeneity

of brain tissue virtually preclude development of a

single, perfectly predictive brain monitor.

Evoked Potentials. Sensory evoked potentials

(EPs), which include somatosensory evoked potentials (SSEPs), brainstem auditory evoked potentials

(BAEPs), and visual evoked potentials (VEPs), and,

more recently, motor evoked potentials (MEPs),

provide a visual representation of the response of
Neurological Injuries

393

neural structures to stimulation. EPs are generated

by integrated neural networks, including the initial

sensory structure, the transmitting pathways, and

cortical and subcortical stimulus-processing centers. As the response to a stimulus is transmitted

centrally, characteristic waveforms are generated

that correspond to structures through which the

stimulus passes. EPs, especially BAEPs and MEPs,

are relatively refractory to insult, although they are

modified by sedatives, narcotics, and anesthetics,

as well as by trauma, hypoxia, or ischemia. Because

obliteration of EPs occurs only under conditions of

profound cerebral ischemia or mechanical trauma,

EP monitoring is one of the most specific ways to

assess neurological integrity. However, EPs are

less sensitive to smaller changes in cerebral (or

spinal cord) oxygen availability.

In patients with head trauma66,67 or spinal cord

injury,68,69 EP monitoring has been employed primarily as a diagnostic and prognostic aid.

Multimodality EPs improve the prognostic accuracy of the clinical examination and measurement of ICP in patients with head injuries.67 With

impending brain death, cortical SSEPs disappear

first; BAEPs disappear only when brain death

is imminent.70 Because BAEPs are resistant to

the effects of barbiturates, EPs assist in assessing

neurological status even in patients in barbiturate

coma.

Electroencephalographic Monitoring. Computerized compression of electroencephalographic

(EEG) data permits frequent, repetitive assessment

with a minimum of specific training. In the most

commonly employed software programs, the data are

displayed as a compressed spectral array (CSA) or

density spectral array (DSA). Because the EEG is

sensitive to drug effects, either unprocessed or processed EEG monitoring can be used to assess sedation in critically ill patients as well as to provide early

evidence of seizure activity or cerebral ischemia.

This equipment remains relatively expensive,

depends on the availability of dedicated technicians, and requires a modest level of sophistication

for interpretation of changes. Like EP monitoring,

EEG monitoring appears to have little value for

either surveillance or goal-directed therapy in patients with head injuries, in contrast to its possible

value for intraoperative monitoring.

Cerebral Blood Flow Monitoring. Although measuring the cerebral blood flow via xenon 133 clearance is a powerful research tool, these measurements do not yet constitute a clinically useful

monitor. Despite the prognostic value of CBF measurements in patients who have suffered closed

head injury, no role has developed for primary

diagnosis, surveillance, or goal-directed management. Among the obstacles to wider use are the

necessity for administering a radionuclide; the technically demanding nature of the measurements;

and the relatively long interval (5–15 min) of stable

conditions required to perform a single measurement, after which an additional several minutes

must pass before subsequent measurements can be

performed.

Intracranial Pressure Monitoring. Because ICP

functions as the outflow pressure for the cerebral

circulation (assuming jugular venous pressure is

lower), ICP bears an important relationship to CBF,

although CBF cannot be directly inferred from

knowledge of ICP and MAP. In more than one third

of patients with head injuries, ICP exceeds 20 mm

Hg, a level thought to be a critical threshold for

clinical intervention.71 If untreated, intracranial

hypertension will increase brain injury by causing

herniation or cerebral hypoperfusion. Although

ICP monitoring has been credited by some investigators72 with an improving prognosis from acute

closed head injury, others73 question whether concurrent improvements in management, rather than

ICP monitoring, explain the improvement. Although the subarachnoid screw74 occasionally generates erroneous information,75 measurement of ICP

is usually considered to be a fundamental part of

the care of patients with severe closed head injury

(ie, GCS score ≤ 8).76 A practical, reliable fiberoptic

ICP monitor has been developed (manufactured by

Camino Laboratories, San Diego, Calif.) that works

well as an intraventricular, subdural, or brain tissue

monitor77 and has relatively little drift of calibration

over periods of 5 days or less.78

Unlike the other modalities previously discussed,

ICP monitoring has been used for surveillance and

for goal-directed therapy. The information is especially valuable in patients in whom neuromuscular

blocking agents are administered as part of treatment to reduce ICP, because such agents preclude a

comprehensive neurological examination. Clinicians have applied systematic, although institutionally specific, protocols for avoidance of intracranial hypertension and for reduction of increased

ICP when a threshold of 15 or 20 mm Hg is exceeded.

Decisions about diuretics, hyperventilation, changes

in the patient’s position, and additional diagnostic

procedures may be influenced by ICP information.

If intracranial hypertension is refractory to conventional therapy, ICP monitoring is one of the alterna-
Anesthesia and Perioperative Care of the Combat Casualty

394

tive techniques used to titrate barbiturate coma,79

although prophylactic barbiturate coma has failed

to improve neurological outcome after head injury.80 Whenever ICP monitoring is employed, the

potential complications, the most important of which

is infection, must be considered. The risk of intracranial infection appears to be less with subarachnoid

bolts than with ventriculostomies, although subcutaneous tunneling may diminish the risk of

infection in the latter procedure.

Brain Metabolic Monitoring. Two forms of brain

metabolic monitoring are available: jugular venous

saturation and near-infrared spectroscopy. Blood

obtained from the jugular venous bulb provides the

cerebral equivalent of “mixed venous” blood. Clinical venipuncture of the jugular venous bulb was

first performed more than 60 years ago.81 Today,

retrograde cannulation of the jugular bulb is a safe,

technically simple procedure.82 CBF, CMRO2, arterial oxygen content (CaO2), and jugular venous oxygen content (CjvO2) are related according to the

following equation:

(CaO2 – CjvO2) • CBF = CMRO2

Rearranged, the equation becomes

CjvO2 = CaO2 – CMRO2 ÷ CBF

Therefore, CjvO2 is a function of CBF, CMRO2, and

arterial oxygenation. SjvO2, which, together with

hemoglobin, determines CjvO2, is a potential monitor of the cerebral circulation. Mixed cerebral venous

blood, like mixed systemic blood, is a global average of effluent from a variety of brain regions and

may not reflect even severe regional hypoperfusion.

Therefore, low SjvO2 is abnormal and suggests the

possibility of cerebral ischemia; but while normal

or elevated SjvO2 is reassuring, it is not adequate

evidence of satisfactory cerebral perfusion. Recent

experience with jugular venous bulb monitoring

suggests that the technique may be appropriate to

guide management.31–33,48–50

Near-infrared spectroscopy, a noninvasive technique that quantifies brain hemoglobin saturation,

may eventually offer the opportunity to provide

effective monitoring for surveillance or goal-directed therapy. Near-infrared light penetrates the

skull and, during transmission through or reflection from brain tissue, undergoes changes in optical

density proportional to the relative concentrations

of oxygenated and deoxygenated hemoglobin in

the tissue beneath the field.83 Although considerable animal and clinical data demonstrate the sensitivity of the technique for the detection of qualitative changes in brain oxygenation,84 clinical application has been delayed because of uncertainties

regarding quantification of the signal. Recent data85

suggest that quantification of the signal may be

practical and that a noninvasive, continuous monitor of cerebral circulatory adequacy will be possible. The availability of an inexpensive, simple-tooperate surveillance monitor as well as a monitor

that could be used for goal-directed therapy provides an opportunity to manage the cerebral circulation as comprehensively as the systemic circulation can now be managed.

General Supportive Care

The essential elements of general supportive care

include airway support, administration of maintenance fluids, provision of sedation and analgesia,

careful head positioning, and frequent turning. If

airway reflexes are impaired, intubation may

prevent aspiration and reduce the likelihood of

hypoxemia or hypocapnia. Pulse oximetry and

capnography facilitate prompt detection of hypoxemia or hypercarbia. Fluid restriction to 50% to

75% of calculated maintenance has long been considered appropriate. Recently, this belief has

been challenged,61 and greater emphasis is now

placed on osmolality rather than fluid restriction.

Because agitation or pain increases CMRO2 and

CBF, and can precipitate intracranial hypertension,

adequate analgesia is particularly important in patients with not only head injuries but also other

painful injuries (eg, surgical wounds or fractured

long bones or ribs). In noncomatose patients in

whom repeated neurological evaluation or direct

observation of mental status is essential, sedatives

and analgesics must be used with great caution.

Neuromuscular blockade necessitates generous,

empirical administration of sedatives and narcotic

analgesics.

The head should not be rotated excessively. Although compression of the jugular venous system

by head rotation produces no change in ICP in

normal individuals, it may impede cerebral venous

drainage and increase ICP in those with reduced

intracranial compliance. Despite the demonstration that head elevation actually reduces CPP in

some patients,86 most patients appear to tolerate a

15° to 30° elevated-head position well.87

An essential aspect of the nursing care of patients

with head injuries is frequent, systematic turning:
Neurological Injuries

395

from the right lateral decubitus position, to the

supine, to the left lateral decubitus position. This

turning reduces decubitus ulceration and pulmonary retention of secretions. If turning-induced

increases in ICP prevent adequate positioning, the

use of a laterally rotating kinetic bed may both

facilitate pulmonary toilet and limit the incidence

of decubitus ulcers. In patients who do not require

the kinetic bed, appropriate skin care includes the

use of a low-pressure mattress pad.

Management of Intracranial Hypertension

Because of the spatial constraints imposed by

the rigid skull, the brain, cerebrospinal fluid, and

cerebral blood volume have little room to expand

without increasing ICP. Head injury may increase

intracranial volume, and therefore ICP, by the

mechanisms listed in Table 16-7. Through extensive monitoring of ventricular fluid pressure in

patients who had chronic intracranial mass lesions

such as gliomas, Nils Lundberg and associates88

demonstrated in 1965 that ICP is not static but

rather is subject to periodic wave phenomena,

the most dangerous of which is the plateau wave.

Plateau waves (sometimes called Lundberg waves),

which often precipitate acute neurological deterioration, appear to result from cerebral vasodilation89 (Figure 16-8) and increases in cerebral

hemispheric blood volume accompanied by a decline in CBF.90

Intracranial hypertension can be managed using

a variety of strategies, all of which are based on the

central concept that reduction of ICP (or improvement of intracranial compliance) can be accomplished by reducing one of the three intracranial

constituents: blood volume, tissue volume, or cerebrospinal fluid volume.

Cerebral blood volume can be reduced using

several techniques. Endotracheal intubation limits

the likelihood of increases in CBF induced by hypoxemia or hypercarbia. Neuromuscular blockade

prevents increases in cerebral venous volume as a

consequence of coughing, straining, or actively exhaling, but neuromuscular blockade has not been

associated with improved outcome in clinical head

injury.91 Head elevation facilitates cerebral venous

drainage but, by reducing venous return, cardiac

output, and MAP, may actually reduce CPP.86 Adequate sedation and analgesia attenuate increases

in CMRO2 and CBF that are produced by painful or

noxious stimulation. Control of fever limits increases in CMRO2 and the accompanying increases

in CBF. Passive hyperventilation, probably overused in the past, acutely reduces CBF and cerebral

blood volume, although CBF tends to return to

original levels despite continued hyperventilation.

Selective diminution of blood volume in the pial

TABLE 16-7

CAUSES OF INTRACRANIAL HYPERTENSION AFTER HEAD TRAUMA

Cause Mechanism

Mass Lesions Local expansion

Intracerebral hematoma

Extraaxial hematoma

Brain Swelling Vascular congestion, hyperemia

Brain Edema

Cytotoxic Cellular swelling secondary to hypoxia or ischemia

Vasogenic Breakdown of blood–brain barrier, interstitial accumulation of protein

Interstitial Hydrocephalus

Secondary Vasodilation

Hypercarbia Increased extracellular hydrogen ion concentration

Hypoxia Mechanism unclear; possibly increased local metabolite (adenosine?) concentration

Hypertension Impaired autoregulation
Anesthesia and Perioperative Care of the Combat Casualty

396

pharmacological therapy, subtemporal decompression may reduce mortality.97 Glucocorticoids, expected to reduce cerebral edema and ICP, have been

ineffective in clinical trials.98,99

Regardless of whether ICP can be reduced, an

intervention that can reduce cerebral oxygen consumption should be therapeutically desirable. Barbiturates in sufficient dosages suppress both CMRO2

and CBF.93–100 Although barbiturates have been

used to control ICP in patients with head injuries,

routine administration of barbiturates did not reduce the incidence of intracranial hypertension or

improve outcome in a well-designed randomized

clinical trial80; in fact, the occurrence of barbiturateinduced hypotension prompted the investigators to

suggest caution. Barbiturates still may have a role

in selected patients who have refractory intracranial hypertension.79

Systemic Circulatory Management

Treatment of hypertension requires careful distinction of the life-threatening Cushing response

from hypertension associated with the typical

hyperdynamic response to head injury. Many commonly used antihypertensive agents, including sodium nitroprusside, nitroglycerin, and hydralazine,

may increase ICP. Although those drugs may be

used if ICP is monitored, alternative agents (such as

the long-acting α-adrenergic and β-adrenergic antagonist, labetalol) may be preferable. Labetalol

reduces blood pressure without increasing ICP.

Acutely, esmolol may provide rapidly reversible

control of blood pressure and heart rate. Adequate

sedation and analgesia may also reduce hypertension and tachycardia.

Ventilatory Management

Although many patients with severe head injury

will ventilate and oxygenate normally if they are

provided with a secure airway, many clinicians

prefer mechanical ventilation. Hyperventilation,

though useful in reducing life-threatening intracranial hypertension, may lead to inadequate CBF as

evidenced by excessive cerebral oxygen extraction44

and, when used as routine therapy, actually worsen

neurological outcome and mortality in comparison

to normocarbia.57 Positive end-expiratory pressure

(PEEP) may be used to manage hypoxemia in patients with head injuries. PEEP-related increases in

ICP are avoided both clinically and experimentally

by head elevation.101,102

Cerebral Perfusion Pressure

100

Torr

o

100

Torr

o

80

Torr

o

Fig. 16-8. Plateau wave during intracranial pressure recording. Shortly after receiving pancuronium (Pavulon,

manufactured by Organon, Inc, West Orange, NJ) 0.4 mg

administered intravenously, systemic arterial pressure

declined slightly. Almost immediately, intracranial pressure increased dramatically, causing a marked decline in

cerebral perfusion pressure. Reprinted with permission

from Rosner MJ, Becker DP. Origin and evolution of

plateau waves: Experimental observations and a theoretical model. J Neurosurg. 1984;60:317.

1 min

Systemic Arterial Pressure

Intracranial Pressure

Pavulon 0.4 mg, administered intravenously

veins has been demonstrated in experimental animals with α2-adrenergic receptor agonists.92

Reduction of brain tissue volume is conventionally achieved by diuresis. Osmotic diuresis, usually

accomplished using mannitol, reduces brain water

primarily in normal brain. A continuous intravenous infusion of mannitol significantly increases

regional CBF without increasing blood pressure or

reducing ICP.93 Maximal reduction of ICP appears

to be achieved by larger dosages of mannitol administered rapidly, particularly if followed by

furosemide.94 Fluid restriction, a conventional part

of therapy, does not reduce brain tissue volume or

ICP in experimental animals.61 Another method

that has been used to reduce brain tissue water and

therefore to manage refractory intracranial hypertension is the administration of hypertonic saline.

In anecdotal reports,95 small volumes of a saline

solution approximating 30% (5.0 mmol/mL) have

produced a prolonged reduction in ICP and improved prerenal azotemia. In children with head

injuries, a 3.0% saline solution reduced ICP significantly.96 If intracranial hypertension is refractory to
Neurological Injuries

397

Many clinicians in North America routinely paralyze patients for at least the first several days of

intensive care to prevent decerebrate and decorticate posturing and active expiration, each of which

is associated with increases in MAP, central venous

pressure, and ICP. The primary disadvantage of

neuromuscular blockade is that it interferes with

clinical neurological examination. However, recent

reports103 warn of prolonged neuromuscular dysfunction in patients who have been paralyzed for

extended intervals. More importantly, evidence92

suggests that neuromuscular blockade may extend

the duration of intensive care of patients with head

injuries without improving outcome.

Seizure Prophylaxis

Although the overall incidence of posttraumatic

seizures is low, most clinicians provide seizure prophylaxis in the acute interval after head injury,

particularly for patients with skull fractures or intracranial hematomas.104 In adults, the prophylactic seizure medication most commonly employed

is phenytoin, in a dose of 100 mg administered

three times daily (therapeutic serum concentration 10–20 μg/mL). Phenobarbital is commonly

added. For the management of acute seizures,

diazepam, lorazepam, or phenytoin are usually

chosen.

In addition to their head trauma per se, casualties

with brain injuries are also at risk for gastrointestinal and pulmonary complications, infections, and

electrolyte and fluid imbalances. Enteral or

parenteral nutritional support is usually required.

The incidence of stress-induced gastrointestinal

bleeding in patients with head injuries is directly

proportional to the severity of the injury.105 Although aggressive antacid therapy or frequent administration of histamine type 2 blocking agents

may be necessary to increase gastric pH, recent

data106 demonstrate that gastric bacterial overgrowth accompanies loss of gastric acidity.

Sucralfate, which provides effective prophylaxis

without causing gastric alkalinization, may be

preferable for ulcer prophylaxis.107

Patients with severe head injury are at risk for

aspiration pneumonitis, noncardiac pulmonary

edema, pulmonary embolism, and barotrauma.

Prevention of aspiration requires gastric decompression and the use of an appropriately inflated,

cuffed endotracheal tube. To limit secretion retention, atelectasis, and secondary infection, mandatory turning and positioning are essential.

An occasional patient with severe head injury

develops the adult respiratory distress syndrome

secondary to either infection or severe intracranial

injury (in which case the syndrome is often called

central neurogenic pulmonary edema). The management of adult respiratory distress syndrome

consists of ventilatory support with PEEP and relief

of intracranial hypertension, if present.

Patients with severe head injury also are at risk

for nonpulmonary infections. Urinary tract infection may result from urinary catheterization. Maxillary sinusitis is surprisingly common among

MEDICAL COMPLICATIONS OF HEAD TRAUMA

nasotracheally intubated patients with head

trauma,108 although a prospective trial showed that

orally intubated patients also have a substantial

incidence.109 Ventriculitis and meningitis complicate trauma, surgical procedures that violate the

dura, and indwelling intraventricular monitoring

devices.

Abnormalities of sodium metabolism are common in patients with acute head injury. Hypernatremia may result from diabetes insipidus (DI)

secondary to trauma or transection of the pituitary

stalk. Typically, traumatic DI follows a three-phase

course, with polyuria occurring initially, followed

by reduced urinary output as stored antidiuretic

hormone is released from the damaged pituitary,

followed finally by prolonged DI.110 Partial deficits

of antidiuretic hormone also occur. The diagnosis

of DI necessitates the demonstration that polyuria

is a physiologically inappropriate response, which

is usually confirmed by the development of

hypovolemia or hypernatremia. If hypernatremia

develops, the free-water deficit should be corrected

slowly. Antidiuretic hormone replacement can be

provided in the form of either aqueous vasopressin

(5–10 units administered intramuscularly every 6–

8 h), lysine vasopressin, or desmopressin (DDAVP,

0.1 mL administered intranasally every 12 to 24 h).

Patients with head injuries frequently develop

hyponatremia, occasionally as the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)111 or excessive intravenous administration of free water, or occasionally, excessive

production of atrial natriuretic peptide.112 The treatment of hyponatremia depends on its cause. Hyponatremia associated with hypovolemia should be

managed with intravenous fluid administration of
Anesthesia and Perioperative Care of the Combat Casualty

398

isotonic fluids. Conversely, patients with SIADH

usually respond to water restriction. Occasionally,

demeclocycline may be necessary to correct

SIADH.113

Despite extensive documentation of hypermetabolism after head injury, the appropriate route

and composition of nutritional support have yet to

be defined. Many questions remain unanswered.

However, most clinicians tend to initiate either enteral or parenteral nutrition as soon as possible after

acute head injury, generally preferring enteral nutrition if tolerated. Because patients with a GCS

score of 4 to 5 require nearly 70% more than normal

predicted resting metabolic requirements,114 positive nitrogen balance may be difficult to achieve.115

Fever further increases metabolic requirements.

Glucocorticoids increase nitrogen wasting.116 When

feeding patients with head injuries, the possibility

of hyperglycemia should be anticipated and glucose should be controlled. Although only descriptive data117 implicate hyperglycemia in worse neurological outcome after head trauma, considerable

experimental and clinical data118 suggest that

hyperglycemia worsens injury in some, but not

all, models of focal and global neurological

ischemia.

Despite good neurological recovery, patients with

head injuries often have persistent cognitive or

emotional deficits or personality changes, particularly if posttraumatic coma results from diffuse

brain injury rather than discrete focal lesions. Recovery of the verbal intelligence quotient usually

begins within a few months and becomes stable

more rapidly than the performance intelligence

quotient, which may continue to improve for a year

or more.119 Memory deficits, which may impair

social interactions and interfere with work performance, usually persist only briefly after minor injuries. In contrast, patients with severe injuries, particularly those involving both temporal lobes, may

have persisting, profound difficulty with both longand short-term memory.120

The most common major neurological findings

in patients who survive head injury are unilateral

cerebral hemispheric dysfunction and cranial nerve

palsies. Factors associated with an increased risk of

epilepsy after closed head injury include intracranial hematomas and depressed skull fractures. Of

patients who develop seizures within 5 years of

injury, nearly 75% will have their first seizure during the first year after injury.104

Good recovery to moderate disability can be anticipated for approximately 50% of adult patients

who enter the hospital with GCS scores of 8 or

lower.2,72 Studies consistently demonstrate increasing mortality with declining GCS scores.2,67,121 Overall, the level of consciousness (as assessed by the

GCS) and brainstem reflexes (pupillary light responses and vestibuloocular or oculocephalic reflexes) correlate highly with patient outcome.2,67

Bilaterally impaired pupillary light responses or

impaired eye movements are associated with a

mortality exceeding 75%.2,67 In patients with intracranial hematomas, signs of brainstem failure, which

would ordinarily predict a dismal outcome, may

reverse rapidly after evacuation of a hematoma.2,67,122

Factors unrelated to the neurological examination

that adversely influence outcome include advanced

age, which also correlates with an increasing risk of

medical complications; hypoxemia, hypocarbia,

hypotension, or anemia on admission to the hospital; and the presence of an intracranial mass lesion

on CT scan.1,2,67

Patients who sustain focal lesions tend to have a

worse outcome than those presenting with diffuse

injury and a similar level of consciousness.123 Patients in whom subdural hematomas are promptly

evacuated (ie, within 4 h) have a 30% mortality;

those operated on later have a 90% mortality.63

More timely diagnosis of epidural hematoma using

CT appears to have reduced mortality.28 More prolonged and severe intracranial hypertension is associated with worse outcome after all head injuries.

Patients in whom ICP consistently exceeds 20 mm

Hg have a mortality exceeding 50%, whereas patients in whom ICP remains continuously lower

than 20 mm Hg have a mortality of only 16%.2,72

Mortality approaches 100% if intracranial hypertension cannot be controlled medically.

To increase cost-effectiveness, future research

should seek to identify those patients who are so

severely impaired that intensive therapy offers no

benefit. A recently tested prognostic scale successfully predicted a fatal outcome (without a single falsely

pessimistic prediction) in 23 of 52 severely patients

with head injuries.124 If confirmed in larger studies,

such data would permit physicians to make informed,

ethical decisions to withhold therapy from certain

well-defined categories of patients, thereby more effectively allocating increasingly scarce resources.

RECOVERY AND OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY
Neurological Injuries

399

Each year in the United States, 10,000 victims of

acute spinal cord injury become paraplegic or quadriplegic. The economic cost of caring for 180,000

acutely and chronically disabled persons is $4 billion per year.125 Most victims of spinal cord injury

are young, usually between 15 and 35 years of

age,126 and male. Patients whose neurological level

of injury is above C-7 are unlikely to return to an

independent existence (Table 16-8).127

Three factors appear to have reduced the acute

mortality of patients with spinal cord injury and

have improved life expectancy127:

1. Patients are more quickly given emergency

care.

2. They are then frequently transferred to

specialized trauma centers, followed by

transfer to specialized rehabilitation facilities.

3. The medical management of cardiovascular, pulmonary, gastrointestinal, and

urinary systems has improved, as has

skin care and the management of infections.

SPINAL CORD INJURY

TABLE 16-8

FUNCTIONAL ABILITY BASED ON LEVEL OF NEUROLOGICAL INJURY

Level of

Injury Functional Ability

C-2–C-4 No movement of upper extremities; some neck control

C-2 requires ventilatory support

C-5 Use of biceps allows feeding and grooming with use of special equipment

C-6 Use of wrist allows independent grooming, driving, and simple meal preparation

C-7 Ability to extend arm can permit independent living

T-1–T-6 Normal hand ability; usually capable of independent living in wheelchair-adapted environment

T-12 Complete trunk control with good sitting balance

Ambulation with long leg braces possible

L-4 Use of hip flexors and quadriceps

Ambulation possible with short leg braces

Spinal reflex activity regulating bladder and bowel usually present in T-12 or above but absent in

L-1 or below

Reprinted with permission from Levinson W, Ward G. Care of spinal-cord injured patients after the acute period. J Gen Int Med.

1989;4:337.

Spinal anatomy can be divided into three biomechanical categories.126 The first portion, the vertebral unit, includes the bones, ligaments, and muscles.

The second unit is composed of the spinal cord,

nerve roots, and membranous elements, including

the dura; and the third, the spinal cord vasculature.

Although these arbitrary divisions are not strictly

accurate, they are useful for conceptualizing spinal

cord injury that results from anatomical damage to

one or more elements.

The vertebral unit of the spinal column is composed of 7 cervical, 12 thoracic, 5 lumbar, and 5

fused sacral vertebrae, and 1 coccygeal element

formed by the fusion of 4 separate bodies.126 With

the exception of the first two cervical and the sacral

vertebrae, articulation is accomplished by the intervertebral discs, which stabilize the synarthroses

between the vertebral bodies; and the posterolateral joints, which are stabilized by their capsules as

well as the intrasupraspinous ligaments and the

ligamentum flava. The structure promotes stability

over a wide range of motion.

The segmental organization of the spinal cord, an

extension of the brainstem, is apparent from the
Anesthesia and Perioperative Care of the Combat Casualty

400

paired spinal nerves, which are formed from the

anterior (motor) roots and the posterior (sensory)

roots, then exit through the intervertebral foramina.

The spinal cord is suspended within the spinal fluid

by nerve roots and ligaments. The pia mater, arachnoid, and dura mater constitute the spinal meninges.

The dura, a fibrous membrane extending from the

cranium, is firmly attached circumferentially at the

foramen magnum, usually closely apposed to the

posterior surfaces of the first and second cervical

vertebrae, and loosely associated with the posterolongitudinal ligament in the lumbar and cervical

regions. The 21 dentate ligaments, which extend

from above the first cervical roots to the region of

the last thoracic roots, attach to the inner surface of

the dura and the lateral surface of the cord, securing

and suspending the cord within the dura. Interposed between the spinal dura and the vertebral

column is the epidural space, which contains veins,

fatty tissue, and ligaments.

The vascular supply of the proximal spinal cord

originates from the vertebral and posterior cerebellar arteries, supplemented regionally by branches

from the thoracic and abdominal aorta and the deep

cervical, intercostal, lumbar, and lateral sacral arteries. These arteries and branches give origin to

lateral spinal arteries, which, in turn, give rise to

anterior and posterior radicular arteries. The paired

anterior radicular arteries enter the spinal cord with

each anterior (motor) root and pass caudad to join

the anterior spinal artery.

The severity of spinal cord injury is determined

by two pathophysiological events: primary mechanical injury and secondary injury. Disruption of the

bony and ligamentous elements of the spinal canal

through flexion, extension, compression, rotation,

shear, or traction injures vascular structures and

axons in direct proportion to the magnitude of the

disruptive force. Secondary injury worsens the

primary mechanical injury as a result of the deleterious effects of hypoxia, hypotension, and progressive vascular and biochemical events that follow

injury. Shortly after experimental cord compression, hyperemia and small hemorrhages appear in

the central gray matter. These areas subsequently

expand, further compromising cord perfusion.

Within 8 hours, edema and infarction spread to the

white matter. The end result of this sequence is

swelling, edema, necrosis, extensive demyelinization, and severe neuronal loss in the central gray

matter.128

Many of the factors implicated in head injury

have also been implicated in spinal cord injury

(Figure 16-9), primary among which is the failure of

cellular adenosine 5’-triphosphate (ATP) stores,

followed by intracellular influx of calcium. With

the influx of calcium, phospholipase A2 is activated, forming arachidonic acid from membrane

phospholipids derived from injured cells. Arachidonic acid disrupts cellular integrity; decreases mitochondrial ATP synthesis; and is metabolized to

form prostaglandins, thromboxanes, leukotrienes,

and free radicals. The free radicals then act directly

to destroy normal cellular components, mediate

platelet aggregation, initiate vasospasm, inhibit

neurotransmitter release, and cause the release of

lysosomal enzymes.129 The complex pathophysiological effects of secondary injury have suggested a

multiplicity of possible therapeutic interventions.

Experimental evidence130 suggests that hyperglycemia is associated with worsened neurological

outcome after experimental spinal cord ischemia,

as it is with cerebral ischemia. In contrast, insulininduced hypoglycemia improves recovery of electrophysiological function after spinal cord ischemia.131

Ethanol, commonly involved in spinal cord injury,

interferes with spinal cord autoregulation, thereby

worsening neurological outcome in ethanol-intoxicated animals.132

After trauma to the vertebral column, neurologically injured patients may be asymptomatic or they

may have complete or incomplete spinal cord injury syndromes. The four most common incomplete syndromes are the Brown-Sequard, acute central cord, anterior cord, and posterior cord

syndromes (Table 16-9).133

Physiological Responses

Cardiovascular

The immediate cardiovascular response to spinal

cord injury is sympathetically mediated tachycardia

and hypertension, followed by hypotension secondary to acute sympathectomy if the lesion is

above T-5. Acute sympathectomy results in slightly

decreased systemic vascular resistance and marked

dilation of the venous capacitance vessels. If the

cord lesion is cephalad to T-4, the input to cardiac

accelerator fibers also is lost, reducing or eliminating compensatory increases in heart rate in response

to hypotension. At times, bradycardia produced by

unopposed vagal tone may result in cardiac arrest,

particularly in association with hypoxemia.134

Pulmonary edema occurs in up to 50% of patients

with cervical spinal cord injury. In experimental

animals, pulmonary edema may result from severe

vasoconstriction and acute pulmonary venous hy-
Neurological Injuries

401

Fig. 16-9. Schematic illustration of proposed mechanisms of secondary spinal cord injury. The processes interact,

ultimately producing a greater deficit than could be attributed to the primary injury alone. Potential sites at which

these interactive pathways could be interrupted are illustrated. Reprinted with permission from Janssen L, Hansebout

RR. Pathogenesis of spinal cord injury and newer treatments: A review. Spine. 1991;14:25.

AO: anti-oxidants

C: calcium channel blockers

DMSO: dimethylsulphoxide

H: hypothermia

O: opiates

S: steroids

pertension accompanying massive sympathetic discharge after high spinal cord injury.135 Researchers 136 have demonstrated that experimental

transection of the spinal cord at the level of C-4

initiates a transient, sympathetically mediated response characterized by a marked increase in MAP

followed by hypotension and increases in pulmonary artery occlusion pressure and extravascular

lung water. A variety of electrocardiographic

changes have been reported, including subendocardial ischemia, shifting pacemaker, atrial fibrillation, ventricular tachycardia, ST-T wave changes,

and multifocal premature ventricular contractions.

Although acute spinal cord injury exerts no direct effects on myocardial function, the loss of sympathetic innervation reduces the ability of the myocardium to tolerate sudden increases in preload and

afterload. In patients in whom hemodynamic

problems persist, particularly if pulmonary

edema is present, pulmonary artery catheterization may clarify the need for additional intravascular volume replacement versus the need for

inotropic support.137

Autonomic Hyperreflexia. As sympathetic nervous system function begins to recover and spinal

shock resolves, usually within 2 to 3 weeks after

injury, patients with spinal cord injury cephalad to

the level of splanchnic sympathetic innervation (T4–T-6) may manifest autonomic hyperreflexia (Exhibit 16-2).138 The pathogenesis of this disorder is

the loss of neurogenic control distal to the level of

the lesion, which, in response to noxious stimuli

(usually visceral) below the level of the lesion, leads

to profound vasoconstriction. Subsequent reflex
Anesthesia and Perioperative Care of the Combat Casualty

402

TABLE 16-9

NEUROLOGICAL SYNDROMES POSSIBLE WITH CERVICAL SPINE INJURY

Syndromes Findings

Brown-Sequard Ipsilateral paralysis

Ipsilateral position and vibration sense loss

Contralateral temperature and pain sense loss

Acute Central Cord Bilateral motor loss, weakness in upper extremities exceeds weakness weakness in lower

extremities

Bladder control loss

Variable sensory loss

Anterior Cord Bilateral motor, pain, and temperature loss

Preserved position and vibration sense

Hyperesthesia below the level of the lesion

Posterior Cord All motor and sensory functions preserved except touch and temperature

Adapted with permission from Hastings RH, Marks JD. Airway management for trauma patients with potential cervical spine

injuries. Anesth Analg. 1991;73:473.

EXHIBIT 16-2

SIGNS AND SYMPTOMS OF AUTONOMIC

HYPERREFLEXIA

Hypertension

Vasoconstriction (below lesion)

Vasodilation (above lesion)

Bradycardia

Dysrhythmia (ectopic beats occurring during

period of heart block)

Sweating (below lesion)

Piloerection (below lesion)

Headache

Shortness of breath

Flushed face and neck

Nausea

Blurred vision

Muscle fasciculations

Convulsions

Loss of consciousness

Adapted with permission from Schreibman DL,

Mackenzie CF. The trauma victim with an acute spinal

cord injury. Problems in Anesthesia. 1990;4:472

TABLE 16-10

PULMONARY AND RESPIRATORY MUSCLE

FUNCTION IN QUADRIPLEGIC PATIENTS

WITH CERVICAL SPINAL CORD INJURY

AT C-4 THROUGH C-7

Variable Predicted Normal Value

(%)

Vital capacity 52 ± 11

FEV1/FVC (%) 85 ± 3

Inspiratory capacity 71 ± 16

Expiratory reserve volume 21 ± 12

Total lung capacity 70 ± 4

Functional residual capacity 86 ± 14

Residual volume 141 ± 20

Maximum voluntary ventilation 49 ± 10

PImax (cm H2O) 64 ± 12*

PEmax (cm H2O) 41 ± 22*

*Values are expressed as absolute units, not as percentages of

predicted normal values

FEV1: forced expiratory volume in 1 s; FEV: forced vital capacity; PImax: maximum inspiratory pressure; PEmax: maximum

expiratory pressure

Adapted with permission from Findley LJ, Rochester DF. The

lungs and neuromuscular and chest wall diseases. In: Murray

JF, Nadel JA, eds. Textbook of Respiratory Medicine. Philadelphia,

Pa: WB Saunders; 1988: 1949.
Neurological Injuries

403

10

8

6

4

2

0

Expiratory Flow Rate (L/s)

100 80 60 40 20 0

Predicted Vital Capacity (%)

Fig. 16-10. A comparison of predicted expiratory flow

rates as a function of predicted vital capacity (closed

circles). Open circles represent data from 11 patients in

the first week after injury; closed triangles represent data

from the same 11 patients 5 months after injury. Reprinted with permission from Ledsome JR, Sharp JN.

Pulmonary function in acute cervical cord injury. Am Rev

Respir Dis. 1981;124:43.

relationship between spinal cord ischemia and the

progression of neurological deficits is unclear. Because of the unique circulation of the spinal cord,

“watershed” areas exist at midpoints of the spinal

arterial circulation, equidistant from the radicular

arteries. Arterial blood flow in the spinal cord

comes from opposite directions, from the cervical

cord vessels above and the paired anterior and

posterior spinal arteries below.147 The lower cervical area, most distant from collateral pathways, is

most vulnerable to ischemia. Researchers148 demonstrated that in monkeys, the area most vulnerable to ischemia was at the level of C-6, resulting

from the compartmental division of blood flow up

and down the anterior spinal artery. Because of

limited collateral flow from the vertebral and intercostal arteries, the cervical cord between C-5 and C8 would be the area most vulnerable to ischemia

when MAP falls below the lower limit for autoregulation. Another area of special concern is the variable portion of the thoracic spinal cord supplied by

the radicularis magna.

SCBF autoregulation has been described as similar to that of cerebral autoregulation, with the range

of 60 to 120 mm Hg representing the autoregulatory

plateau (Figure 16-11).149 Although it is unclear

whether autoregulation of SCBF is impaired after

cord injury, it is likely that the traumatized spinal

activity of the carotid and aortic baroreceptors produces vasodilation above the level of the lesion,

ventricular dysrhythmias, bradycardia, and, occasionally, heart block. Of patients with lesions above

T-7, 66% to 85% manifest hyperreflexia at some

time.138,139 Although the potential for autonomic

hyperreflexia is maximal at approximately 4 weeks

after injury, any patient with spinal cord injury

above T-7 is at risk of exposure to a variety of

visceral stimuli, most commonly distention of a

hollow viscus.140–143 Medical management is first

directed toward eliminating the causative stimuli,

using direct-acting vasodilators such as sodium

nitroprusside, controlling cardiac arrhythmias, or,

during surgery, deepening anesthesia.

Pulmonary System

A lesion at the level of T-1 eliminates the contributions of the intercostal muscles to both inspiration and expiration and of the abdominal oblique

muscles to expiration. Inspiratory reserve volume

and total lung capacity are thereby reduced, as are

expiratory reserve volume and forced vital capacity

(FVC). Table 16-10 illustrates typical pulmonary

function tests from patients with acute injury to the

mid-to-lower spinal cord.144 Although functional

residual capacity increases in both normal and quadriplegic patients as they are tilted upward, the increase in normal persons is accomplished by an

increase in expiratory reserve volume, whereas in

quadriplegic patients, who are unable to assist expiration by actively contracting the abdominal musculature, the increase is produced by an increase in

residual volume.145 Within the first few days after

acute spinal cord injury, FVC typically decreases

somewhat, then begins to recover. Five months

later, both peak expiratory flow rates and FVC are

substantially greater than during the first week

after injury (Figure 16-10).146

Despite considerable compromise of the respiratory musculature, most patients who are able to

generate a normal or nearly normal tidal volume

remain normocarbic. However, hypoxemia occurs

when FVC is lower than 15 mL/kg because coughing and sighing are inadequate. Acute onset of

aspiration, atelectasis, or pneumonia may result in

sudden respiratory compromise.

Spinal Cord Blood Flow

Despite extensive experimental work demonstrating the relationship between acute spinal cord injury and reduced spinal cord blood flow (SCBF), the
Anesthesia and Perioperative Care of the Combat Casualty

404

administration of fluids are essential to reducing

morbidity and mortality. During evaluation and

management, appropriate use of cervical collars,

backboards or vacuum mattresses, sand bags, and

3-in. tape will immobilize the spine and minimize

exacerbation of the injury to the cord until adequate

radiological studies have ruled out injury. Such

studies may not be possible for days or weeks in

patients with multiple trauma.

Once the level of the neurological deficit is established, problems can be anticipated and managed.

Among these, the acute level-dependent systemic

complications of acute spinal cord injury include, as

discussed earlier, loss of sympathetic control of the

vascular tree, left ventricular dysfunction, and respiratory compromise. Long-term problems include

autonomic hyperreflexia, decreased gastrointestinal motility, nutritional depletion, genitourinary

problems, and metabolic dysfunction.

After treating any life-threatening conditions recognized in the primary survey, the medical officer

should then proceed to a secondary survey and

meticulous head-to-toe physical examination. In

comatose patients, concomitant spinal cord injury

may be overlooked, especially if a meticulous neurological exam is not conducted. However, neck pain is

a sensitive, specific indication of cervical spine injury

in awake, cooperative patients (Table 16-11).133 Because 25% to 60% of patients who have sustained

vertebral column injuries have other injuries,137 a

high index of suspicion must be maintained, even

when evaluating an alert, cooperative patient, because the patient may be insensate to an injury

below the level of the injury to the spinal cord. Of

patients who have spinal cord injuries, 49% also

have a concomitant closed head injury.150 Retrospective studies detect a much lower incidence (6%)

of total head injuries associated with spinal cord

injuries, and approximately a 2% incidence of severe closed head injury (GCS score ≤ 8).151 Injuries

of the thoracic spine are associated with multiple

rib fractures, flail chest, or aortic disruption.

In summary, during initial evaluation, a rapid

assessment of spinal cord, head, and other injuries

should be made; the airway and adequate ventilation

assured; supplemental oxygen applied; intravenous

access secured; fluid resuscitation initiated; and expeditious transport arranged to a definitive care facility, ideally a trauma or spinal cord injury center.

Radiological Evaluation

In the recent past, a single, cross-table lateral,

plain cervical spine X-ray examination, which in240

180

140

100

60

20

-20

0 40 80 120 160 190

Perfusion Pressure (mm Hg)

Brain r = .858 P < .0002

Cord r = .850 P < .0002

Central Nervous System

Blood Flow (mL/100 g/min)

Fig. 16-11. Autoregulation of blood flow is similar in both

spinal cord and brain in rats anesthetized with pentobarbital. In both tissues, the autoregulatory plateau

extends from 60 to 120 mm Hg perfusion pressure.

Reprinted with permission from Hickey R, Albin MS,

Bunegin L, Gelineau J. Autoregulation of spinal cord

blood flow: Is the cord a microcosm of the brain? Stroke.

1986;17:1184.

cord, like the traumatized brain, is extremely vulnerable to hypotension.

Initial Care

Initial care of the patient with potential or evident

spinal cord injury consists of three parts: clinical evaluation and stabilization, radiological evaluation, and,

when necessary, airway management. Of course,

depending on the severity of respiratory compromise,

securing the airway may be the first priority.

Clinical Evaluation and Stabilization

Meticulously detailed neurological examinations

must be performed as soon as possible. Serial

examinations will characterize the initial spinal cord

insult, herald extension of injury, and provide prognostic in-formation. Based on knowledge of the

neurological level of injury, physiological responses

can be anticipated.

It is imperative that patients with spinal cord

injury rapidly enter a system in which care is provided by adequately trained, technically proficient

personnel who are attuned to the importance of the

basic principles of trauma care and the importance

of immobilization of the spine, especially if airway

intervention is required. Respiratory support and

the prompt reversal of shock by the intravenous
Neurological Injuries

405

TABLE 16-11

CERVICAL SPINE INJURY AND NECK PAIN IN ALERT TRAUMA PATIENTS

Number of Patients Number of Patients

Primary With With Primary Without

Study C-Spine Injury Neck Pain Study C-Spine Injury Neck Pain

Fisher (1984)* 5 5 Fisher 0 328

Roberge (1988) 6 6 Roberge 0 141

Bayless (1989) 2 2 Bayless 0 122

Bachulis (1987) 65 65 Neifeld (1988) 0 145

Ringenberg (1988) 253 247† Kreipke (1989) 0 324

Lally (1989)‡ 16 16

Rachesky (1987)‡ 21 21

*Numbers in parentheses are the years in which the primary source was published

†Six patients with other painful injuries did not report neck pain

‡Pediatric trauma

Adapted with permission from Hastings RH, Marks JD. Airway management for trauma patients with potential cervical spine

injuries. Anesth Analg. 1991;73:473.

lar process and of abnormalities in the joint and

disk spaces.133 If a patient is able to follow commands, lateral flexion-extension views should

be obtained, as the patient controls head motion.

Until then, rigid immobilization with a hard

cervical collar (eg, the Philadelphia collar, manufactured by Philadelphia Collar, Westville, N.J.) is

cluded all seven cervical vertebrae and the C-7–T-1

interspace, was considered sufficient to assess

cervical spine integrity. However, the sensitivity

of this single view is only 74% to 92% (Table 16-12).

A three-view evaluation, including anteroposterior and odontoid views, permits better assessment

of vertical alignment of the spinous and articuTABLE 16-12

SENSIVITY OF CERVICAL SPINE X-RAY STUDIES

Primary Number of Patients Sensitivity*

Study View With Cervical Spine Injury (%)

Streitwieser (1983)† CTL 44 82

3 Views 38 92

Shaffer (1981) CTL 35 74

Bachulis (1987) CTL 90 77

Ross (1987) CTL 13 85

3 Views 13 92

MacDonald (1990) CTL 92 92

Freemyer (1989) 3 Views 33 91

*Sensitivity = true positives ÷ (true positives + false negatives) • 100 †Numbers in parentheses are the years in which the primary sources were published

CTL: cross-table lateral view; 3 views: cross-table lateral, anteroposterior, and open-mouth

Adapted with permission from Hastings RH, Marks JD. Airway management for trauma patients with potential cervical spine

injuries. Anesth Analg. 1991;73:476.
Anesthesia and Perioperative Care of the Combat Casualty

406

EXHIBIT 16-3

NECESSARY EQUIPMENT FOR

EMERGENCY AIRWAY MANAGEMENT

Laryngoscope with blades of various sizes and

shapes

Endotracheal tubes of various sizes

Endotracheal tube stylet

Oral and nasal airways

Face masks of various sizes

Tonsil-tipped suction handle or suction source

Ambu bag (attached to oxygen source)

Pharmacological adjuncts (drugs drawn up in

syringes)

Reprinted with permission from Grande CM. Airway

management of the trauma patient in the resuscitation

area of the trauma center. Trauma Q. 1988;5(1):38.

indicated, if there is any clinical suspicion of neck

injury.

Computed or conventional tomography supplements plain radiographs that are equivocal or negative despite clinical evidence of cord injury.152–154

The occurrence of spinal cord injury without radiographic evidence of vertebral injury or instability can

be as high as 15% to 70%.155,156 Although MRI is

superior for evaluation of injury to soft tissues, including paravertebral tissue, intervertebral discs and ligaments, the complexity involved in obtaining MRI

scans precludes its use in most acute circumstances.

Airway Management

Despite the simultaneous risks of inadequate

pulmonary function and aggravation of spinal cord

damage, there are no universally accepted approaches to airway management in patients with

acute spinal cord injury. The method chosen in a

specific situation is determined by a variety of factors, among them the severity of physiological compromise, the clinician’s experience and ability, the

availability of specialized equipment, the magnitude and type of associated injuries, the presence of

hemodynamic stability, and the availability of definitive diagnostic information about the cervical

spine.133,157 Because the need to secure the airway

emergently cannot be predicted in advance, a cart

containing necessary equipment should be readily

available (Exhibit 16-3).

The choice among various methods of airway

management depends on the severity of physiological compromise. If a patient is unable to maintain

normoxia and normocarbia, or is actively vomiting

and unable to protect the airway, then direct visualization and orotracheal intubation should be attempted first. Adjunctive medications, such as sedatives, induction agents, or muscle relaxants, should

be used as dictated by the patient’s hemodynamic

status. Cricoid pressure may be used if necessary, but

its vigorous application could produce subluxation

at the injury site. Immobilization of the cervical

spine can be accomplished with manual in-line axial

traction (MIAT),157 a method associated with no

evidence of new or worsened neurological injury

resulting from intubation in more than 3,000 patients.158

Gardner-Wells tongs can also be used for cervical

spine immobilization. If the oral route is impractical

because of injury, edema, or oropharyngeal bleeding,

and an artificial airway is required, emergent surgical cricothyrotomy can be performed; alternatively,

percutaneous needle cricothyrotomy can be used as

a temporizing measure.

If the need for an artificial airway is less acute,

nasotracheal intubation may be performed either

blindly or using fiberoptic guidance. The nasal

route should not be used in the presence of basilar

skull fracture, midface instability, or nasoseptal injury because of the risk that the endotracheal tube will enter the brain55 or cause serious

hemorrhage. Vasoconstriction of the nasal mucosa

can be achieved with the application of nasal decongestant spray (eg, Afrin, manufactured by

Shearing-Plough Health Care Products, Inc., Memphis, Tenn.) or phenylephrine. Topical anesthesia

may alleviate discomfort even in a semicomatose

patient who might otherwise react vigorously to

noxious airway stimulation, thereby precipitating

extension of the spinal cord injury. Fiberoptic

bronchoscopy can be used to facilitate nasotracheal

intubation, assuming that the intubator is skilled

and that there is little blood or foreign material in

the oropharynx.

The nasal route does have some important disadvantages, however. Any mechanical airway manipulation may provoke hypertension, a particular

hazard in a patient with closed head injury and

decreased intracranial compliance. Epistaxis may

be severe, especially in patients who have

coagulopathies. When performed blindly, nasotracheal intubation may damage the larynx. Either

blind or fiberoptically guided nasotracheal

intubation may be time-consuming. Semicomatose,
Neurological Injuries

407

inebriated, or frightened patients may react combatively, risking further injury to the spinal cord.

Prolonged nasotracheal intubation is associated with

maxillary sinusitis and occasional sepsis.

Other methods of placing oral tracheal tubes

such as retrograde wires may be challenging because of associated injuries. Thus, even in circumstances that are not emergent, the method of choice

for tracheal intubation may be orotracheal intubation

in conjunction with MIAT, after denitrogenation,

supplemented by a carefully titrated dose of

thiopental, midazolam, or etomidate, and a neuromuscular blocking agent. Succinylcholine is appropriate if the injury is less than 48 hours old; after 48

hours, the risk of succinylcholine-induced hyperkalemia, potentially a fatal event,159 increases dramatically. A nondepolarizing agent such as vecuronium is preferable if more than 48 hours have

elapsed.

Anesthetic Management

Anesthesia personnel may be confronted with

patients with spinal cord injury at any stage of

resuscitation, just as they may with patients with

head injuries. This section addresses the anesthetic

management of the patient with spinal cord injuries

who does not have a secure airway.

Preoperatively, the most important considerations relate to respiratory compromise, hypotension, and the possibility of associated injuries.

Respiratory compromise may not be evident on

initial examination but may be apparent if the patient is asked to perform a vital-capacity maneuver.

Hypotension is secondary to venodilation and impairment of the usual reflex increase in heart rate

that occurs with hypotension in patients in whom

sympathetic pathways are intact. Associated injuries below the level of the injury may not be recognized because of the absence of pain. Before induction of anesthesia, blood pressure should be restored

with the use of volume expansion. Pressors may

occasionally be necessary. Dopamine tends to constrict the venous system and increase heart rate.

Ephedrine may be useful for short-term stabilization. Atropine is especially useful if bradycardia is

a major factor in hypotension or if severe bradycardia follows airway stimulation.

Monitoring during anesthesia should be determined by the severity of associated injuries and the

availability of equipment. If time and circumstances

permit, direct arterial pressure monitoring will warn

promptly of hypotension. Central venous pressure

monitoring may provide information about the relationship between blood volume and expanded

venous capacitance. Pulse oximetry and capnography provide early warning of deterioration in gas

exchange. Automated, noninvasive blood pressure

monitoring may free anesthesia personnel for other

activities.

Anesthetic induction must preserve hemodynamic stability while securing the airway with minimal risk of aggravating the cervical spine injury.

The initial decision is whether to intubate the patient awake (fiberoptically or blindly) or whether to

proceed with a rapid-sequence induction. Either

should be accompanied by MIAT. Awake intubation, in the absence of MIAT, risks cervical movement when the endotracheal tube enters the trachea

and stimulates coughing. On the other hand, vigorous head movements during direct laryngoscopy

also risk excessive cervical motion.

Potential anesthesia induction agents include

thiopental, etomidate, benzodiazepines, and

ketamine. The effects of anesthetics on perfusion of

the injured spinal cord are not well known. Most

clinicians assume that the effects are similar to the

effects of agents on CBF and CMRO2. Large dosages

of barbiturates may reduce blood pressure, especially in hypovolemic patients. Etomidate provides

prompt induction and is usually well tolerated even

in some hypotensive patients. Benzodiazepines

usually preserve blood pressure. Large dosages

may slow emergence. Cricoid pressure should be

applied during induction and intubation. In a hemodynamically resuscitated patient with acute spinal cord injuries, a reasonable sequence is to

administer thiopental and fentanyl followed by succinylcholine, all while maintaining cricoid pressure. Hyperkalemia resulting from succinylcholine

administration is unlikely after recent (< 24-h old)

spinal cord injury. The incidence increases after 24

hours and plateaus by 12 days. For maintenance,

the effects of volatile anesthetics on spinal perfusion also appear to parallel their effects on CBF and

CMRO2.

Postoperatively, the ability to extubate the patient with a spinal cord injury depends on preoperative respiratory compromise and on the magnitude

and site of surgery. Before extubating the patient

with a cervical cord injury, it is wise to determine

FVC and peak negative pressure.

Management in the Intensive Care Unit

Management in the intensive care unit is intended to limit neurological disability and reduce

the morbidity and mortality of the complica-
Anesthesia and Perioperative Care of the Combat Casualty

408

TABLE 16-13

CAUSE OF DEATH IN THE FIRST MONTH AFTER SPINAL CORD INJURY

95% Confidence

Cause of Death Actual Deaths SMR Limit of SMR

Septicemia 5 500.0 61.7–938.3

Cancer 0 0.0 0.0–0.0

Ischemic heart disease 4 7.7 0.2–15.2

Other heart disease 8 133.3 40.9–225.7

Cerebrovascular disease 4 33.3 0.6–66.0

Diseases of arteries 2 50.0 0.0–119.3

Venous thrombosis and embolism 10 500.0 190.1–809.9

Influenza and pneumonia 12 300.0 130.3–469.7

Other respiratory disease 4 66.7 1.4–132.0

Diseases of digestive system 4 66.7 1.4–132.0

Diseases of urinary system 4 200.0 4.0–396.0

Symptoms and ill-defined conditions 11 275.0 112.5–437.5

Unintentional injuries and suicides 0 0.0 0.0–0.0

Residual 7 24.1 6.2–42.0

Unknown 1

SMR: standardized mortality ratio (actual deaths ÷ predicted deaths • 100)

Adapted with permission from DeVivo MJ, Kartus PL, Stover SL, Rutt RD, Fine PR. Cause of death for patients with spinal cord

injuries. Arch Intern Med. 1989;149:1765.

tions that accompany acute spinal cord injury. It

is necessary to prevent further damage to the

patient’s spinal cord, manage cardiovascular and

pulmonary complications, and control pain. In

the first month after spinal cord injury, which includes the time during which patients are most

likely to be admitted to the intensive care unit,

pneumonia, pulmonary embolism, and sepsis are

the most common factors contributing to death

(Table 16-13).160

In the intensive care unit, monitoring of patients

with acute spinal cord injury consists of careful

cardiovascular monitoring, monitoring of gas exchange, and the use of EPs for diagnosis and prognosis. Pulmonary monitoring is the same as that

used for other critically ill patients, consisting of

pulse oximetry, capnography, and, as necessary,

arterial catheterization to obtain arterial blood gases.

Pulse oximetry may be of particular value in those

patients who become bradycardic in response to

hypoxemia.

Somatosensory evoked potentials (SSEPs),

noninvasive tests of the integrity of spinal cord

transmission, have developed into important diagnostic and prognostic tools in patients with acute

spinal cord injury.161,162 Strictly speaking, SSEPs

cannot be used to monitor acute injuries. Not surprisingly, preservation of SSEPs after injury is consistent with incomplete spinal cord transection and

portends a more favorable outcome than loss of

SSEPs.163 When combined with clinical evaluation of motor function, sensation to pinprick, and

joint position, SSEPs provide greater prognostic

value.69 Although techniques for the use of MEPs

have been developed for humans, few data quantify the likely diagnostic and prognostic value of

this modality.164

Spinal Cord Protection

Because of the progressive hemorrhagic infarction

of the spinal cord that sometimes follows acute

trauma, the pathophysiology of secondary, progressive injury has been extensively investigated

(see Figure 16-9). Of the great variety of interventions that have been attempted after acute spinal cord

injury, several have received particularly intense scrutiny, including localized spinal cord hypothermia,

endogenous opioid antagonists, glucocorticoids, free

radical scavengers, and GM1 ganglioside.
Neurological Injuries

409

nist that does not reverse opioid-mediated analgesia, also exerts a beneficial effect in experimental

spinal cord injury.168,169 However, other researchers170 conclusively demonstrated that, in humans,

naloxone (given as a bolus of 5.4 mg/kg, followed

by an infusion at a rate of 4.0 mg/kg/h for 23 h)

failed to improve neurological outcome in comparison with placebo and methylprednisolone (discussed below) (Table 16-14).

Glucocorticoids. In animals subjected to spinal

cord trauma, glucocorticoids, including dexamethasone and methylprednisolone, have generally exerted therapeutic benefit. As a consequence of

promising data from studies with animals, a

multicenter, double-blind, randomized clinical trial171

compared patients who received “standard”-dose glucocorticoids (100 mg as a bolus followed by daily

administration of 100 mg for 10 d) and patients who

received “high”-dose glucocorticoids (a 1,000-mg bolus followed by 1,000 mg daily for 10 d). There were

Topical Hypothermia. Topical hypothermia was

first investigated more than 25 years ago,165 based

on the assumption that hypothermia would reduce

spinal cord metabolism, thereby decreasing the risk

of infarction, and presumably decreasing the rate of

formation of toxic metabolites.166 Despite experimental evidence in favor of topical hypothermia,

the results in humans have been inconsistent and

discouraging,126 perhaps because of the heterogeneity of human spinal cord injury and the substantial delay before most patients reach treatment facilities.

Opiate Antagonists. Researchers167,168 first reported in the 1980s that endorphins (endogenous

opioids) are involved in the progression of spinal

cord injury and that the administration of naloxone,

an opiate antagonist, increased blood pressure and

SCBF and improved neurological recovery in comparison to results in animals given a saline control.

Thyrotropin-releasing hormone, an opiate antago-

*Scores for motor function range from 0 to 70; scores for sensations of pinprick and touch each range from 29 to 87

†Placebo value is used as the control (reference value) to which MP and naloxone were compared, using an analysis of variance

‡P < .05

MP: methylprednisolone

Adapted with permission from Bracken MB, Shephard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone

or naloxone in the treatment of acute spinal-cord injury. N Engl J Med. 1990;322:1409.

TABLE 16-14

NEUROLOGICAL OUTCOME AT 6 WEEKS AND 6 MONTHS IN PATIENTS TREATED WITHIN 8

HOURS OF INJURY

6 Weeks 6 Months

Category of Injury and Measure* MP Naloxone Placebo† MP Naloxone Placebo†

Plegic with total sensory loss

Number of patients 47 37 46 45 34 44

Motor 6.2‡ 3.2 1.3 10.5‡ 7.5 4.2

Pinprick 5.9 3.0 2.2 9.4‡ 4.2 4.0

Touch 6.8‡ 3.7 2.6 9.7‡ 7.1 4.7

Plegic with partial sensory loss

Number of patients 5 12 6 5 11 6

Motor 14.4 14.1 18.0 23.0 28.9 26.5

Pinprick 11.8 13.9‡ 4.0 11.6 18.4 9.8

Touch 4.4 7.1 0.3 0.0 13.5 5.2

Paretic with variable sensory loss

Number of patients 14 12 17 12 11 17

Motor 18.3‡ 12.7 10.8 24.3‡ 14.5 12.9

Pinprick 10.7 8.2 7.5 14.3 9.6 7.5

Touch 3.8 6.1 1.2 7.6 6.2 1.0
Anesthesia and Perioperative Care of the Combat Casualty

410

no differences in neurological recovery between the

two groups, but wound infections were more prevalent in the patients receiving the higher dose.

A second, randomized, controlled clinical trial170

compared placebo, naloxone, and methylprednisolone given as a bolus of 30 mg/kg, followed by a 23-

hour infusion at a rate of 5.4 mg/kg/h. The protocol differed from the earlier trial171 in two key

respects. First, the initial daily dose was much

greater. Second, the drug was given for only 1 day,

based on the rationale that short-term administration would be associated with fewer wound complications and infections, but would still provide maximal glucocorticoid effect during the most critical

interval. The subjects who received methylprednisolone within 8 hours of injury showed a significantly greater improvement in motor function and

sensation to pinprick and touch than those who

received the placebo, naloxone, or methylprednisolone more than 8 hours after injury (see Table

16-14).170 Although the differences in the second

clinical methylprednisolone trial were statistically

significant, they were not dramatic; however, even

small differences in motor function may result in

major differences in the rehabilitation and quality

of life of patients with spinal cord injury. In this

study, the short-term administration of glucocorticoid was not associated with increased risk of infection or gastrointestinal bleeding.

Free Radical Scavengers. Considerable experimental evidence suggests that postischemic oxidative injury may contribute to neurological damage.

A variety of methods have been used in an attempt

to reduce oxidative stress, particularly to reduce the

accumulation of oxygen free radicals in injured tissue.

One of the more effective experimental interventions

has been the use of 21-aminosteroids, compounds that

are derived chemically from glucocorticoids, but lack

glucocorticoid activity and are potent inhibitors of

iron-dependent lipid perioxidation.172

GM1 Ganglioside. Most of the pharmacological

interventions that have been directed at acute spinal cord injury have been designed to reduce the

rapid hemorrhage and infarction of the spinal gray

matter that occur in the first few hours after injury.

However, an alternative strategy is to attempt to

preserve the axons passing through white matter

adjacent to the site of injury.173 Experimental data

suggest that preservation of as few as 6% of axons

prevents distal muscle paralysis and preserves normal movement.174 Enhanced recovery or repair of

damage to long tracts in the spinal cord potentially

can be initiated 72 hours or more after the primary

injury.175 In a prospective, randomized, placebocontrolled, double-blind trial, GM1 ganglioside

(monosialotetrahexosylganglioside), a compound

that enhances neurological recovery after experimental spinal cord injury,176 substantially enhanced

improvement, assessed using the Frankel scale

and the American Spinal Injury Association

(ASIA) motor scores, after 1 year of follow-up.173

The improvement appeared to be attributable to

restoration of useful motor function in initially paralyzed muscles rather than to improving strength in

paretic muscles. The overall improvement in ASIA

motor score (Figure 16-12) reflects a trend toward

greater improvement in lower extremity function

than in upper extremity function (Figure 16-13).

The magnitude of the beneficial effect of GM1 ganglioside in this study was approximately twice as

great as that reported earlier with high-dose methylprednisolone. Because the patients in the GM1 ganglioside trial received relatively small, probably

ineffective, dosages of methylprednisolone, these

data raise the exciting possibility that the combination of acutely administered high-dose glucocorticoids and the subsequent administration of GM1 ganglioside could produce greater improvement than

either agent alone.

Fig. 16-12. Changes in the American Spinal Injury Association

(ASIA) motor score in patients treated with GM1 ganglioside

(open symbols) and a placebo (solid symbols) in the 12 months

after their entry into the study. The upper curves (circles)

show unadjusted improvement and demonstrate that the two

groups were significantly different at admission into the

study (ie, the patients receiving GM1 ganglioside were more

severely injured). After adjustment for the imbalance in scores

at entry, the improvement is apparent. The error bars represent 95% confidence intervals. Reprinted with permission

from Geisler FH, Dorsey FC, Coleman WP. Recovery of motor

function after spinal-cord injury—a randomized, placebocontrolled trial with GM-1 ganglioside. N Engl J Med.

1991;324:1835.

Months from Study Entry

ASIA Motor Score

Improvement

Absolute score

0 1 2 3 4 5 6 7 8 9 10 11 12

100

90

80

70

60

50

40

30

20

10

0

-10
Neurological Injuries

411

Lower Limbs Upper Limbs

Months from Study Entry

Improvement in Motor Score

Fig. 16-13. Comparison in the improvement of motor

score, assessed using the American Spinal Injuries Association (ASIA) score, in the upper and lower limbs in

patients with cervical injuries who were randomized to

receive GM1 ganglioside (open triangles) and a placebo

(solid triangles). A trend toward a drug effect in the score

for the lower extremities was not observed in the upper

extremities. The error bars represent 95% confidence

intervals. Reprinted with permission from Geisler FH,

Dorsey FC, Coleman WP. Recovery of motor function

after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med.

1991;324:1836.

assessment of intervascular volume and cardiac

output during the acute phase of spinal shock.

However, because of the significant contribution of

infection to morbidity and mortality in patients

with spinal cord injury, invasive monitoring should

be used judiciously. Fluid challenges have been

recommended to assess cardiac function in conjunction with pulmonary artery catheterization.137

Using this approach, fluid is administered in 250-

mL increments at 50 mL/min until cardiac filling

pressures rise and remain at least 2.0 mm Hg greater

than the preinfusion level. Fluid challenges help to

define the need for inotropic support as well as for

additional volume administration in hypotensive

patients.

Pulmonary Management

In patients with spinal cord injury, the major

cause of early death—respiratory failure secondary

to muscle paralysis—depends on the level of injury,

and may either progress or regress over time. Frequently, diaphragmatic function gradually and progressively deteriorates for up to 5 days after injury,

often accelerated by other pulmonary complications such as pulmonary edema or aspiration of

vomitus. Serial measurements of FVC and peak

negative inspiratory pressure permit early recognition of deterioration and prompt intubation and

mechanical ventilation before hypoxemia and

hypercarbia occur. In general, patients with spinal

cord injury require ventilatory assistance when FVC

is lower than 15 mL/kg or when a peak negative

inspiratory pressure of –25 cm H2O cannot be attained. Likewise, measurements of FVC and peak

negative inspiratory pressure used to guide weaning from mechanical ventilation (Table 16-15).138

Nosocomial pulmonary infections occur not only

as a result of respiratory compromise but also because of the relative immunocompromise that accompanies severe trauma. Close attention to pulmonary toilet, including chest physiotherapy,

positioning, and tracheal suctioning, is essential,179

especially in those patients in whom postinjury

FVC barely exceeds the threshold for intubation (15

mL/kg). The use of rotating beds, especially for

patients in cervical traction, may promote better

pulmonary toilet, although controlled studies180 of

this expensive intervention in patients with head

injuries have been less encouraging than earlier,

uncontrolled studies. Care must be taken during

rotational therapy to maintain hemodynamic stability in patients who have high cervical lesions or

spinal shock.

Cardiovascular Management

Cardiovascular management in the intensive care

unit is directed at maintaining intravascular volume, providing inotropic support as needed, avoiding excessive fluid administration, and carefully

avoiding or promptly treating bradycardia—especially that associated with suctioning in hypoxic

patients. The syndrome of spinal shock, which may

continue to be a problem for as long as 6 weeks after

injury, requires adequate intravascular volume expansion and, in some cases, vasoactive drugs such

as dopamine (which, even in low dosages, acts as a

venoconstrictor). Particular care should be taken

with the positioning of patients in the spinal shock

phase of acute spinal cord injury, because sudden

changes in position, particularly to the upright position, may result in sudden hemodynamic instability.177,178 Hemodynamic deterioration resulting from bradycardia may necessitate intermittent

or prophylactic treatment with atropine, especially during vagotonic maneuvers such as tracheal suctioning, endotracheal intubation, or rectal examination.

In the acute phase of management, an arterial

catheter may be useful for blood pressure monitoring and management of blood gases. Pulmonary

artery catheterization may be useful for short-term
Anesthesia and Perioperative Care of the Combat Casualty

412

TABLE 16-15

WEANING CRITERIA FOR REMOVAL FROM

MECHANICAL VENTILATION

Weaning Criterion Acceptable Value

Maximum inspiratory force > –20 cm H2O

Maximum expiratory force > +20 cm H2O

Vital capacity > 1,000 mL

Expiratory value > 10 L/s (level

dependent)

PaO2/FIO2 > 250

Lung/thoracic cage compliance > 30 mL/cm H2O

Adapted with permission from Schreibman DL, Mackenzie CF.

The trauma victim with an acute spinal cord injury. Problems in

Anesthesia. 1990;4:471.

For patients who require intubation for pulmonary support, the choice of neuromuscular blocking

agents is important. After the first 24 to 48 hours

after injury, succinylcholine-induced hyperkalemia

can be life threatening.159,181 Although the exact

onset of this response in humans has not been elucidated, studies182 in a primate model suggest that

the critical time may be as soon as 4 days after

injury, with half of the peak increases (approximately 2.8 mEq/L above baseline) in serum potassium occurring at 8 days, and peak increases (approximately 5.5 mEq/L above baseline) occurring

at 14 days after injury. The interval during which

patients with spinal cord injury remain vulnerable

to the hyperkalemic response to succinylcholine is

unclear but certainly extends more than 6 months

after injury.

Prevention of venous thrombosis and pulmonary embolism, major causes of morbidity and

mortality after spinal cord injury,177 is an important part of the management of patients with

acute injury to the spinal cord. Low-molecularweight heparin is safer and more effective than

conventional heparin in the prevention of

thromboembolism in patients who have complete

motor paralysis.183

Pain Syndromes

Three types of pain syndromes commonly develop in the postacute phase of spinal cord injury127,184:

1. Pain at the site of trauma is usually well

localized, tender and responds well to analgesics, heat, and transcutaneous electrical nerve stimulation (TENS).

2. Radicular or dermatomal pain presumably

results from irritation of nerve roots by

adhesive arachnoiditis. Variable symptoms include sharp, burning pain with hypersensitivity in a radicular distribution.

TENS may be effective. Carbamazepine is

also often effective. Other analgesics are

sometimes helpful, but often not.

3. Posttraumatic spinal deafferentation pain

is a diffuse burning or dysesthesia below

the level of injury. Often difficult to control,

deafferentation pain is resistant to analgesics but may respond to phenytoin, carbamazepine, or amitriptyline. Approaches such

as dorsal root entry zone (DREZ) surgery

are reserved for refractory cases.

The specific management of pain associated with

spinal injury beyond the acute stages is beyond the

scope of this chapter, which deals with trauma

anesthesia for combat casualties, not their rehabilitation. However, Rehabilitation of the Injured Soldier,

185 a volume in the Textbook of Military Medicine

series, discusses the problem in detail.

Medical Complications

The sequelae of spinal cord injury include numerous and varied medical complications, such

as those of the gastrointestinal and genitourinary

systems, electrolyte abnormalities, decubitus ulcers, and the need for nutritional and emotional

support.

Gastrointestinal System

Gastric atony usually accompanies spinal shock;

intestinal motility may be reduced for several weeks

after injury. Because air swallowing leading to

gastric distention is frequently a problem in the

early course of hospitalization after spinal cord

injury, placement of a nasogastric tube is mandatory. Replacement of nasogastric drainage is important to prevent hypokalemic, hypochloremic

metabolic alkalosis. Prophylaxis against stress

gastritis and ulceration can be accomplished using

antacids, H2 blocking agents, or sucralfate. In 1989,
Neurological Injuries

413

Hyponatremia, a mild, common complication

after spinal cord injury, occasionally results in severe water intoxication.187 In part, this reflects a

tendency of patients with spinal cord injuries toward high fluid intake, in addition to impaired freewater excretion.

Decubitus Ulceration

Pressure sores are a common, potentially expensive, and morbid complication of spinal cord injury.127

Typically occurring over bony prominences, decubitus

ulcers can be prevented by proper skin care, compulsive skin inspection, and judicious application of

weight-relieving equipment. Patients in the intensive

care unit should be repositioned every 2 hours, both to

prevent decubitus ulceration and to prevent stasis of

secretions. Air-bladder beds such as Roto-rest R and

Kin-air R beds (manufactured by Hill-ROM, Charlotte, N.C.) are usually the best solution.

Nutritional Support

Adequate provision of calories and nitrogen prevents muscle wasting and therefore facilitates management of pulmonary status and later rehabilitation. Although not specifically demonstrated in

patients with spinal cord injury, improved nutritional status and limitation of catabolism should

reduce morbidity and mortality. Early use of the

gastrointestinal tract, which can be accomplished

with small nasoenteric tubes, feeding jejunostomy

tubes placed during surgery, or, in some instances,

conventional nasogastric tubes, is preferable to intravenous hyperalimentation. Metoclopramide may facilitate feeding by improving gastric emptying. Intravenous hyperalimentation should be considered only

a short-term alternative used to reduce catabolism in

patients unable to tolerate enteral feedings.

Emotional Support

The psychological impact of spinal cord injury

cannot be overstated. Most casualties with spinal

cord injury are young, previously healthy, active

individuals; they all require psychological and emotional support in dealing with sudden disability

and prolonged rehabilitation. Early involvement of

patients, friends, and family is imperative.188 Without consistent support, rehabilitation may prove

difficult or futile.

researchers186 reported that early provision of total

energy requirements through adequate oral or

parenteral nutrition decreased the incidence of gastrointestinal bleeding in patients with spinal cord

injury.

In cervical and high–thoracic spinal cord injury,

the sympathetic control of the transverse colon and

rectum is disrupted, as is parasympathetic control

of the descending and rectosigmoid colon. Loss of

voluntary control of the external anal sphincter,

pelvic floor, and abdominal wall impairs normal

bowel evacuation. Early after the injury, reflex

emptying of the colon usually occurs. Later, fecal

impaction secondary to ineffective distal colonic

peristalsis can manifest as absent bowel movements

or diarrheal flow around an obstructing fecal mass.127

Rarely, colonic distention may result in autonomic

hyperreflexia. A high-fiber diet, generous fluid

intake, and stool softeners usually adequately prevent fecal impaction.

Genitourinary System

All patients with complete spinal cord injury and

many patients with incomplete cord injury syndromes require urinary bladder drainage to relieve

distention. Because of recurrent urinary tract infections associated with long-term, indwelling bladder

catheters, intermittent bladder catheterization is initiated after initial stabilization. Recurrent, chronic

urinary tract infections remain a cause of morbidity

and mortality.127,177,178 Renal function often deteriorates as a result of repeated urinary tract infections

and stone formation, which may be secondary to

either infection or hypercalciuria. Pyelonephritis

and chronic renal insufficiency or failure may lead

to proteinuria, electrolyte losses, and uremia.

Electrolyte Abnormalities

Immobility stimulates calcium release from

bone and, therefore, hypercalcemia usually manifests within 2 weeks after spinal cord injury;

hypercalcemia eventually leads to nephrolithiasis

and frequently becomes a chronic problem. Because

of osteoporosis, a consequence of bone demineralization, patients with spinal cord injuries are vulnerable

to fractures that occur with minimal trauma. Care

must be taken when these patients are transferred and positioned in association with their

routine care, examinations, or surgery.
Anesthesia and Perioperative Care of the Combat Casualty

414

SUMMARY

Advances in strategic planning, logistical support, and the miniaturization of devices permit the

modern fighting force to have relatively sophisticated medical services in close support of forward

operations. Despite the fact that mobile army surgical hospitals or equivalent hospital units may be

located close to the front lines of engagement,

thereby reducing evacuation time and facilitating

the initiation of definitive care, combat conditions

do not always permit immediate evacuation. Initial

triage and treatment may be required in technologically constrained circumstances. At this level, the

art of medicine must be most critically practiced

within the strict guidelines of military triage. Thus,

when confronted with the neurologically injured

patient, time or other injuries may already have

rendered the casualty with head or spinal cord

injuries unsalvageable owing to intervening hypoxia, hypercarbia, or hypotension. Regardless of

the apparent prognosis, resuscitation should proceed aggressively, keeping in mind the vulnerability of the acutely injured central nervous system to

systemic insults.

Airway obstruction, hypoventilation, and hypoxia should be presumed to be present in any

comatose patient with a head injury. Concomitant

spinal cord injury should be suspected. The airway

should be secured quickly. Oral intubation is best

accomplished with accompanying manual in-line

cervical traction. Nasal intubation is relatively

contraindicated in the patient with apparent facial

fractures. During intubation, cricoid pressure may

limit the likelihood of aspiration of stomach contents. Ventilation should account for increased

oxygen consumption.

Hemodynamic resuscitation must be accomplished promptly. Cerebral ischemia or intracranial hypertension may result from inadequately

treated hypotension. Volume administration, especially in the form of 0.9% saline or more hypertonic solutions, is unlikely to increase ICP. If

hypotension and bradycardia are related to acute

spinal cord injury, then volume expansion, ephedrine, and atropine will restore perfusion pressure. Hypertension, a common physiological

response to acute head injury, usually requires

no treatment and may represent a physiological

reflex that maintains CPP in the face of increased

ICP.

If intracranial hypertension is suspected, then

hyperventilation should be used; however, routine

hyperventilation is unnecessary and ineffective.

Mannitol, with or without furosemide, helps to

maintain high serum osmolality, which is the key to

reducing the volume of normal brain tissue, thereby

lowering ICP.

Although barbiturates (which decrease CMRO2,

act as cerebral vasoconstrictors, and reduce ICP)

may be useful in inducing anesthesia in normovolemic patients, they do not improve outcome if

used routinely in all patients with head injuries.

Benzodiazepines or etomidate represent appropriate alternatives for induction of anesthesia or sedation during intubation. Etomidate may be particularly useful in patients who are hypovolemic.

Working in an austere combat environment with

limited material and equipment can be stressful to

military medical personnel; however, the lives of

many critically injured individuals can be saved

and their neurological function preserved.

Contributing Author

Colonel William Bergman, M.D., Medical Corps, U.S. Army, Neurosurgical Consultant to The Surgeon

General, Walter Reed Army Medical Center, Washington, D. C. 20307-5001

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1984;252:793–795.
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EYE INJURIES

Chapter 17

INTRODUCTION

ANATOMY AND PHYSIOLOGY OF THE EYE

EFFECT OF DRUGS ON INTRAOCULAR PRESSURE

ANESTHETIC MANAGEMENT OF THE CASUALTY WITH AN OPEN EYE

INJURY

Intubation and Induction

Emergence

INTERACTIONS WITH OTHER DRUGS

PERIOPERATIVE OPHTHALMIC COMPLICATIONS

Corneal Abrasion

Acute Angle-Closure Glaucoma

Supraorbital Nerve Compression

Retinal Artery Thrombosis

Oculocardiac Reflex

SUMMARY

JOHN D. CURRENT, M.D.*

*Colonel, Medical Corps, U.S. Army Reserve; formerly, Chief, Anesthesia and Operative Service, Brooke Army Medical Center, Fort Sam

Houston, Texas 78234; currently, Associate Professor, Department of Anesthesiology, University of Mississippi Medical Center, 2500 North

State Street, Jackson, Mississippi 39216
Anesthesia and Perioperative Care of the Combat Casualty

426

INTRODUCTION

There are two basic types of eye injuries: penetrating (ie, open) and nonpenetrating. As a rule,

nonpenetrating injuries are less severe than penetrating injuries, but either type can lead to blindness. Nonpenetrating eye injuries, in which the

globe remains intact, are usually lesser anestheticmanagement dilemmas than penetrating eye injuries, in which the globe is disrupted. Nonpenetrating

eye injuries include injuries to the eye and orbit and

can be as minor as a corneal abrasion or eyelid

ecchymosis, or as severe as retinal detachment,

vitreous hemorrhage, or optic nerve injury. Penetrating injuries—the major source of serious combat eye injuries—are more common than might be

thought, given the small portion of the body surface

area that the eyes occupy. In wars of this century,

from 3% to 9% of surviving casualties have been

treated for eye injuries.1 The higher-than-expected

frequency of eye injuries reflects not only the exposed

position of the head in combat but also the vulnerability of the eyes. They are a “soft” target: an injury of the

same magnitude in another part of the body might

very well be ignored. Finally, the increased use on

the modern battlefield of explosive munitions that

are designed to produce large numbers of small

fragments is an additional factor that predisposes

to the unexpectedly high frequency of eye injuries.

Of combat eye casualties in the Vietnam War in

whom the mechanism of their eye injury was known,

79% were injured by fragments, with rockets, mortars, mines, and grenades being the most common

explosive munitions responsible; bullets were the

source of only 6% of eye wounds.1 This is interesting because in living casualties, bullets caused a

much smaller proportion of eye injuries compared

with their overall casualty-generating importance

during the Vietnam War (ie, bullets were the wounding agents in 30%–50% of living casualties).2 These

percentages would seem to be contradictory, but

the reason for the seeming contradiction is simple:

compared with a small fragment, a bullet that injures the eye is much more likely to continue on into

contiguous organs such as the brain, where it frequently causes a fatal injury.2 The fragments that

cause eye injuries in living casualties are, in fact,

quite small: 70% of the fragments had a mass of 1 to

100 mg.1

Many combat casualties present with corneal

foreign bodies, the removal of which rarely requires

the participation of an anesthesiologist. In the Vietnam surgical experience, the most common indication (50%) for a major eye operation was the presence of a disrupted globe requiring an enucleation

(Figure 17-1). Other common indications for operation were corneal or scleral lacerations (19%), the

presence of an intraocular foreign body (15%), and

the laceration of the ocular adnexa (11%). Outside

the combat zone, the most common indications for

a major eye operation in a combat casualty with an

eye injury were the presence of an intraocular foreign body (37%) and the need for enucleation (35%).

The indication for the latter was severe infection

that had destroyed the globe or the threat of sympathetic ophthalmia.1 To care properly for such patients, the military anesthesiologist must know of

the anatomy and physiology of the eye.

ANATOMY AND PHYSIOLOGY OF THE EYE

eye (ie, restricting compliance). The net effect is

analogous to changes in intracranial pressure:

hypercarbia causes increased intraocular pressure

(IOP).4 Similarly, hyperventilation causes choroidal arterial vasoconstriction with a concomitant

decrease in IOP.5 The surgeon may request hyperventilation by the anesthesiologist in hopes of reducing IOP. However, the effect is quantitatively

small. There is only about a 0.1 torr change in IOP

for every torr change in the partial pressure of

carbon dioxide in the arteries (PaCO2), which limits

the value of the practice.6

Hypoxia also causes choroidal arterial vasodilation and a rise in IOP. Interestingly enough, hypothermia does not increase IOP; on the contrary,

The eye is divided into the posterior and anterior

chambers by the iris and the pupil (Figure 17-2).

Aqueous humor fills the anterior and posterior

chambers. The aqueous humor is formed primarily

by the ciliary processes, with some contribution

from the iris. It flows forward through the pupil to

the angle formed by the iris and cornea. There, a

trabecular meshwork containing the spaces of

Fontana (ie, the spatia anguli iridocornealis) is the

site of absorption of the aqueous humor. The aqueous humor then flows through the canal of Schlemm

(ie, the sinus venosus sclerae), eventually reaching

the venous system. Hypercarbia results in the dilation of choroidal arteries.3 The sclera forms a fairly

rigid structure, restricting volume changes in the
Eye Injuries

427

a b

c d

e

hypothermia reduces the production of aqueous

humor and also causes vasoconstriction, which result in a lowered IOP.7 Increasing venous pressure

may profoundly increase IOP. This occurs by impeding outflow of aqueous humor through the canal of Schlemm, compression of the eye by episcleral

veins, and dilation of choroidal vessels. Any straining, coughing, vomiting, and so forth during

laryngoscopy or emergence from anesthesia may

result in dramatic increases in IOP via this mechanism.8 Increases of 30 to 40 torr have been recorded.

External compression of the eye (eg, pressure from

a mask or the increased tone of extraocular muscles)

may increase IOP. This is particularly hazardous in

the case of an open eye injury because the potential

exists for loss of eye contents. However, when the

globe is intact, the ophthalmologist may use several

minutes of eye compression to reduce IOP and

make the globe less rigid. This likely occurs owing

to expression of aqueous humor from the anterior

chamber.

The discussion of IOP has so far emphasized

mechanical and vascular determinants. However,

the normal mechanism for control of IOP involves

the balance between production and drainage of the

aqueous humor. Most pharmacological means to

control IOP affect this balance. Normal IOP is 10 to

22 torr; IOP is considered abnormal if it exceeds 25

Fig. 17-1. This series of photographs, taken during the

Vietnam War, shows the typical operative management of

a disrupted globe. (a) The casualty, who suffered a destructive injury caused by multiple fragment wounds to the left

side of his face, is intubated and ready for surgery. (b) The

ophthalmologist is inspecting the casualty’s eye; the globe

is totally disrupted. (c) Enucleation is in progress. (d) The

orbital contents are being extracted. (e) A prosthesis has

been placed in the socket. Photographs: Swan Vietnam

Surgical Slide Collection.
Anesthesia and Perioperative Care of the Combat Casualty

428

Fig. 17-2. Anterior segment of the eye. Reprinted with permission from Paton D, Craig JA. Management of cataracts.

Clinical Symposia. 1990;42(4):6.

torr. The method of measurement may influence

the IOP determined. Indentation (ie, Schiötz) tonometry may cause expression of aqueous humor and a

reduction of IOP with repeated determinations.

Older studies using indentation tonometry for measuring the effects of drugs and anesthetic agents on

IOP have been called into question because of this.

The more accepted and accurate method for determination of IOP is applanation tonometry, particularly if repeated measurements are necessary.7
Eye Injuries

429

EFFECT OF DRUGS ON INTRAOCULAR PRESSURE

crease the IOP or leave it unchanged. An intravenous bolus dose of ketamine has been found14 to

result in a 37% increase in IOP, with the maximum

increase occurring 15 minutes after the injection.

Other researchers15,16 have presented data that suggest that heavily premedicated patients do not experience increases in IOP with ketamine. However,

blepharospasm, nystagmus, or laryngospasm may

make ketamine undesirable for ophthalmic surgery.

Succinylcholine has been found17 to increase IOP.

This increase is not temporally related to muscle

fasciculations18; indeed, pretreatment with acetazolamide or propranolol have been reported19 to

prevent a rise in IOP after succinylcholine without

preventing fasciculations. Increases in IOP with

succinylcholine have been reported20–24 after adequate pretreatment doses of nondepolarizing

muscle relaxants. Attempts to use small, “selftaming” doses of succinylcholine have themselves

resulted in elevation of IOP.25 Furthermore, pretreatment with lidocaine does not prevent increases

of IOP following succinylcholine administration.26

In contrast, nondepolarizing muscle relaxants

consistently reduce—or at worst, do not change—

IOP.27–31 Intubating doses of atracurium and

vecuronium do not raise IOP, but the intubation

itself may.32 The increase-in-IOP response to

laryngoscopy and intubation in children was prevented by the addition of intravenous lidocaine (1.5

mg/kg) to the standard induction sequence of

thiopental and pancuronium.33

Miotic agents such as echothiophate (Phospholine

Iodide, manufactured by Wyeth-Ayerst Laboratories, Philadelphia, Pa.) and acetylcholine are used

to lower IOP. The constriction of the pupil tightens

the iris, stretching the trabecular meshwork of the

spaces of Fontana. The net result is a facilitation of

drainage of the aqueous humor and lowering of

IOP. Aqueous humor production may be decreased

with ophthalmic preparations of epinephrine,

timolol, and acetazolamide. The production of aqueous humor is an active process using the carbonic

anhydrase enzyme system. Therefore, acetazolamide can reduce IOP by reducing the production of aqueous humor by 50%. Acute lowering of

IOP may be achieved through the use of osmotic

agents. These drugs act to increase plasma oncotic

pressure, which diminishes aqueous production,

albeit transiently. Mannitol is the drug most commonly used, although urea and glycerol have also

been used.3 They all require catheter drainage of

the urinary bladder intraoperatively. Furthermore,

glycerol, given orally, increases the volume of stomach contents and adds a potential risk for regurgitation and aspiration under general anesthesia.

General anesthetic agents, particularly barbiturates and potent inhalational agents have consistently been shown9–11 to reduce IOP. In humans,

intravenous administration of etomidate has been

shown12 to consistently and significantly lower the

IOP. Intravenous lidocaine has been shown13 to

reduce the IOP response to laryngoscopy and

intubation. Ketamine, on the other hand, may inANESTHETIC MANAGEMENT OF THE CASUALTY WITH AN OPEN EYE INJURY

Anesthetic management may play an important

role in the outcome of ophthalmic surgery. The

surgeon requires a motionless eye and a bloodless

field. Any coughing, bucking, straining, or vomiting by a patient with an open eye injury may result

in hemorrhage and loss of vitreous or vision.8

 Eye

injuries in which the globe is fully perforated require especially careful anesthetic management to

avoid extrusion of intraocular contents and resultant permanent disability. The anesthesiologist must

certainly avoid applying external pressure to the

eye, such as during application of the face mask. It

is also helpful to the surgeon to have the endotracheal tube out of the way, using a downwarddirected tube such as a RAE (named for its developers: Ring, Adair, and Elwyn; manufactured by

Mallinckrodt Critical Care, Great Falls, N.Y.) or an

armored tube. Of simultaneous concern to the

military anesthesiologist is the likelihood that the

casualty will have a full stomach. If time and the

patient’s medical condition permits, aspiration prophylaxis should be considered. Oral or intramuscular histamine 2 blocking agents may be administered to the patient, preferably 1.5 to 2 hours prior

to the procedure. Ranitidine 150 mg, administered

orally, or 50 mg, administered intramuscularly (or

alternatively, cimetidine 300 mg, administered

orally, or 150 mg, administered intramuscularly),

should increase the pH of the stomach contents.

Famotidine 20 mg, administered orally or intravenously, will also reduce gastric volume and increase pH. Reglan 10 mg, administrated orally or
Anesthesia and Perioperative Care of the Combat Casualty

430

of atracurium suffered hypotension and tachycardia.

The Metubine-pancuronium combination takes

advantage of the synergistic effect of these two

drugs to reduce the amount of each necessary to

achieve rapid relaxation. Pretreatment with

Metubine 0.05 mg/kg followed by pancuronium

0.06 mg/kg gives adequate intubation conditions

nearly as rapidly as the larger-dose pancuronium

technique but does not produce so prolonged a

period of paralysis. Other researchers40 pretreated

patients with metocurine 0.03 mg/kg and 3 minutes

later administered pancuronium 0.08 mg/kg. They

found that 95% depression of twitch height occurred in 70 seconds and all patients had good-toexcellent intubating conditions. However, these

patients’ recovery to 25% twitch height required

100 minutes.

The use of the priming principle has been advocated for patients with open eye injuries.41 A

defasciculating dose of an intermediate-duration

nondepolarizer is followed 3 to 5 minutes later with

a larger dose, 1.5- to 2-fold larger than the usual

intubating dose.36 This gives a fairly rapid onset of

muscle relaxation but not as rapid as that produced

by succinylcholine.

One group of researchers42 found that additional thiopental improved intubating conditions

when using the priming principle with atracurium.

Furthermore, other researchers43 found that priming with atracurium did not significantly improve

intubating conditions, and recommended that it

not be done. This may reflect the importance of

deep anesthesia in securing favorable intubating

conditions without increasing IOP.42 The duration of the blockade is much shorter than that obtained with pancuronium, although postoperative

ventilation could be necessary following short

procedures. At recommended doses, atracurium may occasionally result in adverse hemodynamic changes. Therefore, I suggest the use of

vecuronium 0.01 mg/kg as a priming dose, followed in 3 to 5 minutes with 0.2 mg/kg. There

should be virtually no hemodynamic consequences

from the vecuronium.

Whether succinylcholine should be used in the

patient with open eye injuries remains an issue of

debate. Although some researchers44 have reported

considerable experience with the use of a pretreatment dose of curare followed by succinylcholine in

the patient with open eye injuries with neither loss

of vitreous nor aspiration, others45 consider this

intravenously, may reduce the volume of stomach

contents by promotion of gastric emptying. Administration of a nonparticulate antacid (ie, Bicitra,

manufactured by Baker Norton Pharmaceuticals,

Inc, Miami, Fla., 30 mL, administered orally) will

effectively increase the pH of stomach contents

although at the expense of a small increase in gastric

volume.

Intubation and Induction

Retrobulbar block is contraindicated due to the

risk of external pressure causing extrusion of eye

contents. Indeed, retrobulbar block itself may be

complicated by global perforation.34 Similarly,

awake intubation is contraindicated due to the real

risk of coughing during topical anesthesia or airway insertion. There is a general agreement that

the best approach is to perform endotracheal

intubation with a rapid-sequence induction of anesthesia and cricoid pressure.35 Care must be taken in

the application of cricoid pressure to avoid both

occluding venous return from the head and, possibly, increasing the IOP. The controversy surrounds

the choice of muscle relaxant selected to facilitate

intubation. The thiopental-pancuronium induction

sequence is the standard against which other techniques must be compared.36 If hemodynamic stability permits, a relatively large dose of thiopental

may lessen the likelihood of any patient reaction to

laryngoscopy or intubation. Administration of

pancuronium 0.15 mg/kg should allow intubation

within 90 seconds. The patient should be counseled

regarding the possibilities that the relaxation could

outlast the procedure and therefore that postoperative intubation and ventilation might be required.

The likelihood of tachycardia may make this technique undesirable in patients with coronary artery

disease.37

Variations on this nondepolarizing sequence include (a) large-dose atracurium or vecuronium,38

(b) Metubine-pancuronium combination (Metubine

Iodide, manufactured by Dista Products Co., Indianapolis, Ind.), and (c) the priming principle. Researchers39 who studied onset time and intubating conditions using atracurium 1.5 mg/kg and

vecuronium 0.25 mg/kg found onset time of

95% twitch depression to average 56 and 64 seconds, respectively. Intubating conditions at 60 seconds were somewhat better with vecuronium,

but were satisfactory with either regimen. They

noted that 40% of the patients receiving that dose
Eye Injuries

431

pathetic and cardiac depression. The safest induction technique for these patients will generally be

scopolamine and a muscle relaxant alone.

No single induction technique is suitable for all

trauma situations. Often, the medical officer will be

confronted with a combination of injuries and conditions that make choosing the best anesthetic-induction technique difficult. Examples would be a

patient with a head injury and a full stomach, a

patient with an open eye injury and a displaced

mandibular fracture, and an uncooperative patient

with bleeding and possible cervical spine injury. In

situations such as these, the medical officer must

decide which conditions are of overriding importance and select the most appropriate airway-management technique and anesthetic plan for those

particular conditions.

Emergence

Although modern ophthalmic wound closure can

withstand bucking and straining by the patient, it

seems best to avoid these on awakening to minimize the risk of vitreous loss.3 Deep extubation may

be considered in the patient known to have an

empty stomach but this is not the usual circumstance, as all battlefield casualties are assumed to

have a full stomach. Intravenous lidocaine may be

helpful in minimizing the patient’s reaction to the

endotracheal tube. A dose of 1.5 mg/kg should be

used; this seldom causes prolonged emergence.

Other measures that may be considered include

emptying the stomach by gastric tube while the

patient is still paralyzed and anesthetized, and using an antiemetic such as droperidol.

approach to be controversial. Nevertheless, investigators46 reporting in 1990 suggest that the rapidsequence induction technique modifies the effect of

succinylcholine on IOP resulting in no loss of vitreous. They believe that both (a) scrupulous attention

to adequate depth of anesthesia with thiopental and

(b) waiting until complete paralysis is instituted

with succinylcholine before laryngoscopy and

intubation permit safe intubation, as had been demonstrated44 in 1985. Adequate depth of anesthesia

avoids the likelihood of coughing, straining, and

grimace, which are likely to be more problematic

than the effects of succinylcholine in the anesthetized patient.46

A large dose of thiopental should be used in the

hemodynamically stable patient, assuring adequate

depth of anesthesia and minimizing any response

to laryngoscopy and intubation. The addition of

alfentanil 20 μg/kg has been found useful in reducing the response to tracheal intubation.47 Awake

intubation is inadvisable in patients with open eye

injuriesbecause any cough or straining could result

in loss of ocular contents. Similarly, retrobulbar

block is contraindicated because the block itself

may increase the IOP due to extrinsic pressure on

the globe. Furthermore, blepharospasm, grimace,

or perforation of the globe may occur,48 and the

operator may not be able to minimize hemorrhage

by applying manual pressure.

Patients with severe hypovolemia from acute

blood loss may not tolerate standard anestheticinduction techniques. Severe hypotension or cardiac arrest may occur if the patient is given a hypnotic induction such as ketamine, which causes

cardiac depression, or thiopental, which causes symINTERACTIONS WITH OTHER DRUGS

Many of the ophthalmic agents introduced into

the eye may be absorbed systemically, resulting in

cardiovascular or metabolic effects. Timolol is a βadrenergic blocking agent used in the treatment of

glaucoma. The use of this agent may cause systemic

beta-blockade, with bronchospasm or bradycardia

possible. It is important that the military trauma

anesthesiologist be aware of this fact, but, in most

cases, timolol certainly does not need to be discontinued preoperatively. The ophthalmologist may

apply phenylephrine eyedrops to dilate the pupil

perioperatively. Concentrations as high as 10% are

available; however, occasional systemic manifestations occur (hypertension or bradycardia or both).

Caution in use is advised. Perhaps a diplomatic

request to the surgeon to use the lowest effective

concentration may be made. An ophthalmic drug

very interesting to the anesthesiologist is the miotic

agent Phospholine Iodide. This long-acting pseudocholinesterase inhibitor may still have systemic effects up to 6 weeks after discontinuation.37 This drug

prolongs the effects of succinylcholine, trimetaphan,

and ester local anesthetics, all of which depend on

pseudocholinesterase for termination of action.
Anesthesia and Perioperative Care of the Combat Casualty

432

PERIOPERATIVE OPHTHALMIC COMPLICATIONS

Corneal Abrasion

The most common perioperative ophthalmic complication is corneal abrasion, to which two factors

contribute: basal tear production is greatly reduced,

and the protective eyelid closure reflex is lost under

general anesthesia. The corneal abrasion will often

occur in the inferior one third of the globe, which is

the area exposed when the eyelids are allowed to

remain partially open. Preventive measures to avoid

corneal abrasions include closure of the eyelids and

instillation of some type of artificial tears. Many

techniques have been suggested to keep the eyelids

closed, including taping, suturing, or patching the

eyelids. Aqueous artificial tear solutions have to be

reapplied during long procedures, as they are not

long retained in the eye. For this reason, bland

ointments are more commonly used, although there

may be a small likelihood of allergic reactions to

preservatives used in these preparations.6

Acute Angle-Closure Glaucoma

In postoperative patients, it may be important to

distinguish the painful eye associated with a corneal abrasion from that occurring with acute glaucoma. The corneal abrasion often is accompanied

by pain aggravated by blinking and rapid eye movement, tearing, and the sensation of a foreign body.

An area of dullness may be seen on examination. In

acute glaucoma, the cornea may be dull and reddened, and the pupil may be dilated. The patient

may complain of headache and pain around the eye.

A loss of vision may be recorded.

There are two types of glaucoma: open angle and

closed angle. Both have the common feature of

abnormally elevated IOP. In closed-angle glaucoma, the iris is bulged or folded forward, blocking

the aqueous flow into the trabecular meshwork. An

acutely swollen lens or pupillary dilation may result from this aqueous humor obstruction. Anesthetic care of such patients includes instilling miotic

agents,8 which constrict the pupil and promote aqueous drainage; avoiding venous congestion (eg, keep

the patient’s head up, do not allow the patient to

perform the Valsalva maneuver, and prevent the

patient from bucking or coughing)19; and carefully

managing intravenous fluid administration to prevent overhydration. Neither atropine nor glycopyrrolate in the usual premedication dosages have

been found to worsen IOP with either type of glaucoma; nor have they been implicated when used in

combination with anticholinesterases for reversal

of neuromuscular blockade.8 However, scopolamine has been found to have a greater mydriatic

effect than atropine and should not be used in

patients with glaucoma. This effect of scopolamine

may be more problematic in white than in black

patients.49 Open-angle glaucoma is associated with

scarring or endothelial thickening of the trabecular

meshwork, resulting in obstruction to aqueous humor outflow. Anesthetic considerations are the

same as with closed-angle glaucoma with the addition of avoiding hypotension, because these patients are prone to thrombosis of the retinal artery.

Supraorbital Nerve Compression

Another potential postoperative complication is

supraorbital nerve compression. This may occur

due to improper positioning of the patient or incorrect placement of the face mask or mask straps

during anesthesia. The patient may complain of

periorbital numbness and edema may be noted.

Fortunately, this problem usually resolves without

treatment, although it may require some weeks.

Retinal Artery Thrombosis

A much worse complication is retinal artery

thrombosis. This complication is more likely to

occur in the patient with elevated IOP (eg, in a

patient with glaucoma). Retinal artery thrombosis

has also been associated with the use of deliberate

hypotension.6

 It is most important to ensure that no

pressure is applied to the eye of the anesthetized

patient, such as occurs in the prone position.

Oculocardiac Reflex

An oculocardiac reflex has been described and is

occasionally seen in patients who are undergoing

eye surgery. This reflex is elicited by traction on the

extraocular muscles, pressure on the globe, pinching of the conjunctiva, or placement of a retrobulbar

block. The afferent limb of this reflex involves the

ciliary nerves and ganglion, the ophthalmic branch

of the trigeminal nerve, the trigeminal ganglion,

and, finally, the main sensory nucleus of the trigeminal nerve near the fourth ventricle.6 The efferent

impulses are conducted down the vagus nerve,

resulting in bradycardia or arrhythmias such as
Eye Injuries

433

junctional rhythm, atrioventricular block, ventricular bigeminy, or even cardiac standstill. This reflex

is seen more frequently in children than in adults.

Furthermore, hypercarbia or hypoxemia may increase the likelihood or severity of the response to

the eliciting stimulus. Usual premedication doses

of atropine given intramuscularly are of no value in

preventing this reflex. However, intravenously

administered atropine or glycopyrrolate, given prior

to the application of a stimulus, modifies or prevents the response. Routine use is controversial in

the adult and is seldom done. Rather, most anesthesiologists take advantage of the easy fatigability of

this reflex in the management of bradycardia or

arrhythmias resulting therefrom. Asking the surgeon to halt manipulations long enough for the

reflex to diminish and then proceeding is feasible.

Adequacy of oxygenation and ventilation should be

checked. If the reflex recurs or is severe, then

intravenous atropine may be given.37

SUMMARY

Penetrating missiles in the form of small fragments are the most common cause of eye injuries in

combat casualties who require the services of military trauma anesthesiologists. Not only does the

missile itself directly destroy ocular tissue, but the

wound tract into the globe also serves as an opening

through which intraocular contents may be extruded, causing irreversible injury. This secondary

complication can occur when IOP is acutely elevated by coughing, bucking, or straining, and its

occurrence has also been reported during intubation

and emergence from anesthesia. IOP may also be

altered pharmacologically. Miotic agents, barbiturates, inhalational anesthetic agents, and nondepolarizing muscle relaxants all decrease IOP, while

an increase follows the use of succinylcholine.

The great majority of combat casualties with eye

injuries will require general endotracheal anesthesia; for this, the thiopental-pancuronium induction

sequence is the standard of choice, as it minimizes

the risk of an acute increase in IOP. Bucking and

straining during extubation should be avoided, but

deep extubation is not usually possible because

each battlefield casualty is assumed to have a full

stomach.

Military trauma anesthesiologists need to be

aware of the potential for such perioperative complications as corneal abrasions, acute angle-closure

glaucoma, supraorbital nerve compression, retinal

artery thrombosis, and the oculocardiac reflex.

Careful planning and attention to detail by the

military anesthesiologist will prevent or reduce loss

of vision and promote the rapid return to duty of

soldiers with eye injuries.

REFERENCES

1. LaPiana F. Colonel, Medical Corps, US Army, Walter Reed Army Medical Center, Washington, DC. Unpublished analysis prepared for the Center of Military History, US Department of the Army, Washington, DC, 1985.

2. Bellamy RF. Colonel, Medical Corps, US Army, Walter Reed Army Medical Center, Washington, DC. Unpublished analysis of Wound Data and Munitions Effectiveness Team database. Personal communication, June

1994.

3. Holloway KB. Control of the eye during general anaesthesia for intraocular surgery. Br J Anaesth. 1980;52:671–

679.

4. Samuel JR, Beaugie A. Effect of carbon dioxide on the intraocular pressure in man during general anaesthesia.

Br J Ophthal. 1974;58:62–67.

5. Adams AK, Barnett KC. Anaesthesia and intraocular pressure. Anaesthesia. 1966;21:202–210.

6. McCammon RL. Anesthetic considerations in the presence of ocular disease. In: American Society of Anesthesiologists Refresher Courses in Anesthesiology. Philadelphia, Pa: JB Lippincott; 1980: 127–137.

7. Cunningham AJ, Barry P. Intraocular pressure—physiology and implications for anaesthetic management. Can

Anaesth Soc J. 1986;33:195–208.

8. Adams AK, Jones RM. Anaesthesia for eye surgery: General considerations. Br J Anaesth. 1980;52:663–669.
Anesthesia and Perioperative Care of the Combat Casualty

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9. Schreuder M, Linssen GH. Intra-ocular pressure and anaesthesia. Anaesthesia. 1972;27:165–170.

10. Runciman JC, Bowen-Wright RM, Welsh NH, Downing JW. Intra-ocular pressure changes during halothane and

enflurane anaesthesia. Br J Anaesth. 1978;50:371–374.

11. Magora F, Collins VJ. The influence of general anesthetic agents on intraocular pressure in man. Arch

Ophthalmol. 1961;66:806–811.

12. Oji EO, Holdcroft A. The ocular effects of etomidate. Anaesthesia. 1979;34:245–249.

13. Lerman J, Kiskis AA. Lidocaine attenuates the intraocular pressure response to rapid intubation in children. Can

Anaesth Soc J. 1985;32:339–345.

14. Yoshikawa K, Murai Y. The effect of ketamine on intraocular pressure in children. Anesth Analg. 1971;50:199–202.

15. Peuler M, Glass DD, Arens JF. Ketamine and intraocular pressure. Anesthesiology. 1975;43:575–578.

16. Ausinsch B, Rayburn RL, Munson ES, Levy NS. Ketamine and intraocular pressure in children. Anesth Analg.

1976;55:773–775.

17. Katz RL, Eakins KE. The actions of neuromuscular blocking agents on extraocular muscle and intraocular

pressure. Proc R Soc Med. 1969;62:1217–1220.

18. Pandey K, Badola RP, Kumar S. Time course of intraocular hypertension produced by suxamethonium. Br J

Anaesth. 1972;44:191–195.

19. Carballo AS. Succinylcholine and acetazolamide (Diamox) in anaesthesia for ocular surgery. Can Anaesth Soc J.

1965;12:486–498.

20. Donlon JV. Anesthesia factors affecting intraocular pressure. Anesthesiol Rev. 1981;8:13–18.

21. Cook JH. The effect of suxamethonium on intraocular pressure. Anaesthesia. 1981;36:359–365.

22. Meyers EF, Krupin T, Johnson M, Zink H. Failure of nondepolarizing neuromuscular blockers to inhibit

succinylcholine-induced increased intraocular pressure. Anesthesiology. 1978;48:149–151.

23. Bowen DJ, McGrand JC, Hamilton AG. Intraocular pressures after suxamethonium and endotracheal intubation.

Anaesthesia. 1978;33:518–522.

24. Bowen DJ, McGrand JC, Palmer RJ. Intraocular pressures after suxamethonium and endotracheal intubation in

patients pretreated with pancuronium. Br J Anaesth. 1976;48:1201–1205.

25. Meyers EF, Singer P, Otto A. A controlled study of the effect of succinylcholine self-taming on intraocular

pressure. Anesthesiology. 1980;53:72–74.

26. Smith B, Babinski M, Leano N. The effect of lidocaine on succinylcholine-induced rise in intraocular pressure.

Can Anaesth Soc J. 1979;26:482–483.

27. Tattersall MP, Manus NJ, Jackson DM. The effect of atracurium or fazadinium on intra-ocular pressure.

Anaesthesia. 1985;40:805–807.

28. Balamoutsos NG, Tsakona H, Kanakoudes PS, Iliadelis E, Georgiades CG. Alcuronium and intraocular

pressure. Anesth Analg. 1983;62:521–523.

29. Couch JA, Eltringham RJ, Magauran DM. The effect of thiopentone and fazadinium on intraocular pressure.

Anaesthesia. 1979;34:586–590.
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30. George R, Nursingh A, Downing JW, Welsh NH. Non-depolarizing neuromuscular blockers and the eye: A

study of intraocular pressure. Br J Anaesth. 1979;51:789–792.

31. Maharaj RJ, Humphrey D, Kaplan N, et al. Effects of atracurium on intraocular pressure. Br J Anaesth.

1984;56:459–462.

32. Schneider MJ, Stirt JA, Finholt DA. Atracurium, vecuronium and intraocular pressure in humans. Anesth Analg.

1986;65:877–882.

33. Lerman J, Kiskis AA. Lidocaine attenuates the intraocular pressure response to rapid intubation in children. Can

Anaesth Soc J. 1985;32:339–345.

34. Ramsay RC, Knobloch WH. Ocular perforation following retrobulbar anesthesia for retinal detachment surgery.

Am J Ophthalmol. 1978;86:61–64.

35. Barr AM, Thornley BA. Thiopentone and suxamethonium crash induction. Anaesthesia. 1976;31:23–29.

36. Barr AM, Thornley BA. Thiopentone and pancuronium crash induction. Anaesthesia. 1978;33:25–31.

37. McGoldrick KE. Current concepts in anesthesia for ophthalmic surgery. Anesth Rev. 1980;7:7–16.

38. Abbott MA, Samuel JR. The control of intra-ocular pressure during the induction of anaesthesia for emergency

eye surgery. Anaesthesia. 1987;42:1008–1012.

39. Lennon RL, Olson RA, Gronert GA. Atracurium or vecuronium for rapid sequence endotracheal intubation.

Anesthesiology. 1986;64:510–513.

40. Mehta MP, Choi WW, Gergis SD, Sokoll MD, Adolphson AJ. Facilitation of rapid endotracheal intubations with

divided doses of nondepolarizing neuromuscular blocking drugs. Anesthesiology. 1985;62:392–395.

41. Schwarz S, Ilias W, Lackner F, Mayrhofer O, Foldes FF. Rapid tracheal intubation with vecuronium: The priming

principle. Anesthesiology. 1985;62:388–391.

42. Naguib M, Abdulatif M, Gyasi HK, Absgood GH. Priming with atracurium: Improving intubating conditions

with additional doses of thiopental. Anesth Analg. 1986;65:1295–1299.

43. Sosis M, Larijani G, Marr AT. Priming with atracurium. Anesth Analg. 1987;66:329–332.

44. Libonati MM, Leahy JJ, Ellison N. The use of succinylcholine in open eye surgery. Anesthesiology. 1985;62:637–

640.

45. Weiner MJ, Olk RJ, Meyers EF. Anesthesia for open eye surgery. Anesthesiology. 1986;65:109–110.

46. Calobrisi BL, Lebowitz P. Muscle relaxants and the open globe. Int Anesthesiol Clin. 1990;28:83–87.

47. Morton NS, Hamilton WFD. Alfentanil in an anaesthetic technique for penetrating eye injuries. Anaesthesia.

1986;41:1148–1151.

48. Zaturansky B, Hyams S. Perforation of the globe during the injection of local anesthesia. Ophthalmic Surg.

1987;18:585–588.

49. Garde JF, Aston R, Endler GC, Sison OS. Racial mydriatic response to belladonna premedication. Anesth Analg.

1978;57:572–576.
437

Injuries to the Face and Neck

Chapter 18

INJURIES TO THE FACE AND NECK

INTRODUCTION

FACIAL FRACTURES

Mandibular Fractures

Nasal Fractures

Maxillary Fractures

Zygomatic Fractures

NECK INJURIES

Airway Injuries

Vascular Injuries

Nerve Injuries

Esophageal Injuries

CERVICAL SPINE INJURIES

Cervical Vertebral Injuries

Cervical Spinal Cord Injuries

Evaluation of Cervical Spine Injuries

Management of Blunt Cervical Spine Injuries

ASSOCIATED INJURIES

Neurological Injuries

Ocular Injuries

Other Injuries

AIRWAY MANAGEMENT

Mask Ventilation

Tracheal Intubation

Transtracheal Jet Ventilation

Cricothyroidotomy

Tracheostomy

PERIOPERATIVE ANESTHETIC MANAGEMENT

Local and Regional Anesthesia

General Anesthesia

Intraoperative Airway Management

Postoperative Airway Management

SUMMARY

*Lieutenant Colonel, Medical Corps, U.S. Army; Staff Anesthesiologist, Walter Reed Army Medical Center, Washington, D. C. 20307-5001

MICHAEL D. MATSON, M.D.*
Anesthesia and Perioperative Care of the Combat Casualty

438

INTRODUCTION

Anesthesiologists in both the civilian and military communities sometimes encounter casualties

with trauma to the face and neck. In the civilian

sector, injuries to the face and neck are most commonly the result of blunt trauma from automobile

and motorcycle accidents. In the military, injuries

to the face and neck are primarily the result of

penetrating missiles. During World War I, facial

injuries often occurred when soldiers were (a) shot

in the head as they peered out of their trenches1 or

(b) struck by large chunks of metal from the detonation of random-fragmentation shells. Such traumata were usually rapidly fatal because the missile,

by virtue of its high kinetic energy, did not stop on

entering the soldier’s face or neck but continued on

into the brain or cervical spine (Figure 18-1).2

Injuries to the face and neck in more recent military conflicts such as the Vietnam War have increasingly been the result of so-called improved

fragmentation munitions such as grenades, mortars, and artillery shells.1,3 Improved fragmentation munitions are designed to generate large numbers of small (< 1 cm), light (< 1 g) fragments. Thus,

the typical living casualty in a modern war who

has ballistic trauma to the face or neck—and who

survives long enough to be evacuated from the

battlefield—has one to a few benign-appearing wounds. The damage appears to be limited to

a sinus, an orbit, a few teeth, or the soft tissue of

the pharynx or neck. Nevertheless, these benignappearing injuries may be life threatening (Figure

18-2).

Casualties with face and neck wounds can challenge the anesthesiologist. Establishment of an

airway and adequate ventilation in these patients

can be difficult (Figure 18-3), and supervenient

factors such as the following can complicate management:

• hemorrhage,

• risk of aspiration,

• associated injuries,

• difficult intubation,

• tissue debris and foreign material obstructing the airway, and

• an unstable cervical spine.

Associated injuries—especially those of the head,

but also those to other parts of the body—are common. Once the airway is secure, care of the associated injuries will frequently be more immediately

important than care of the actual face and neck

injuries themselves. Management of casualties with

multiple injuries can be complicated by hemorrhage, hypovolemic shock, increased intracranial

pressure, or disturbances of other body systems.

The care of these patients, as with other trauma

patients, should be in accordance with Advanced

Trauma Life Support (ATLS) guidelines.4

 The

perioperative management of casualties with injuries to the face and neck should follow this sequence

of steps:

1. Assess the airway and establish patency, if

necessary.

2. Assess breathing and provide or support

ventilation, if necessary.

Fig. 18-1. Wounds of the face caused by high-velocity

missiles have a propensity to involve the nearby anatomical structures. This soldier was killed during the

Vietnam War when a bullet fired from an AK47 (7.62 mm)

entered his lower jaw, passed through the fifth cervical

vertebra, and transected his spinal cord. Photograph:

Wound Data and Munitions Effectiveness Team slide

collection.
439

Injuries to the Face and Neck

Fig. 18-2. (a) This casualty was wounded during the Vietnam War by three small fragments produced by an exploding,

improved-fragmentation hand grenade. One fragment entered his left orbit and caused an injury that was treated by

enucleation. Two additional fragments struck the right side of his neck, where one lacerated the right common carotid

artery. (b) The radiograph (taken at the third-echelon surgical hospital) clearly shows how the expanding hematoma

caused tracheal displacement. This casualty was treated before his airway was compromised. Photographs: Wound

Data and Munitions Effectiveness Team slide collection.

a b

a b

Fig. 18-3. (a) This casualty from the Vietnam War sustained a tangential gunshot wound of the right side of his

face. Obstruction of his airway by blood and tissue fragments indicated the need for immediate airway control,

but neither oral nor nasal intubation was possible in the

field. The casualty was transported in the prone position

(to prevent aspiration of blood) until an emergency tracheotomy could be performed at a third-echelon surgical

hospital. (b) The great destruction caused by the gunshot

wound is apparent in this anteroposterior radiograph.

Note that a goodly portion of the right mandible is

missing. Many artifacts are present in the radiograph;

however, the arrow indicates a fragment in the casualty’s

maxillary sinus. Photographs: Wound Data and Munitions Effectiveness Team slide collection.
Anesthesia and Perioperative Care of the Combat Casualty

440

3. Assess circulation and control life-threatening bleeding.

4. Assess the level of consciousness and pupillary size and reaction.

5. Provide resuscitation as needed.

6. Evaluate in detail for

• head and neurological injury,

• maxillofacial injury,

• neck injury,

• chest injury,

• abdominal injury,

• genitorectal injury,

• injury of the extremities, and

• other injuries.

7. Prioritize injuries and plan coordinated,

definitive care.

FACIAL FRACTURES

Fractures are common in facial trauma. Lowenergy blunt impacts tend to cause isolated fractures (ie, fractures of the nose or mandible). Highenergy blunt or penetrating impacts can cause

panfacial or multiple fractures (ie, combinations of

Le Fort fractures, naso-orbital-ethmoid fractures,

and frontal bone fractures).

Mandibular Fractures

Mandibular fracture are common facial injuries.

In the military, mandibular fractures can occur as a

result of vehicular trauma, fragmentation blasts,

and other causes. The force of the impact is redistributed as the mandible is fractured and displaced;

thus, skull fractures are less common with mandibular fractures than with maxillary fractures.1

Fractures of the mandible may be unilateral, bilateral, or comminuted. Unilateral fractures are relatively stable. Bilateral and comminuted fractures

tend to be unstable. Patients with displaced fractures of the mandible present with malocclusion.

They may also have pain, swelling, crepitation, and

drooling. Loss of support for the base of the tongue

can lead to airway obstruction, as can edema and

hematomas. Trismus secondary to pain, edema, or

hematomas can occur with mandibular fractures

and can greatly complicate airway management.

The swallowing mechanism can be impaired and

that, combined with bleeding and hypersecretion of

the salivary glands, can increase the risk of aspiration. Patients with mandibular fractures are also

likely to require intermaxillary wiring, which further complicates perioperative airway management.

Nasal Fractures

Nasal fractures are also common facial injuries.

Signs of nasal fracture include nasal deformity,

epistaxis, hematoma of the nasal dorsum, and

crepitance of the nasal bone. Significant hemorrhage can occur with nasal fractures and, in the

obtunded patient, can lead to airway obstruction or

aspiration. Obstruction of the nasal air passage can

also occur as a result of bony deformities and edema.

Blind nasal intubation should be avoided in patients with nasal fractures or intranasal injuries. If

nasal intubation is required, then evaluation of the

nasal passage via fiberscope or other means should

precede tube placement.

Maxillary Fractures

Maxillary fractures are common in civilian practice (eg, automobile accidents). In the military,

maxillary fractures might occur if a truck were to

detonate a mine. These injuries are generally caused

by high-energy trauma and are often associated

with skull fractures or intracranial injuries. As the

maxilla is a very vascular structure, fracture and

disruption can cause significant bleeding both

preoperatively and intraoperatively. Manifestations of maxillary fractures include malocclusion,

marked facial swelling, mobility of the midface,

palpable malalignment of the bone edges (ie, stepoff deformities) at the fracture site, and ecchymosis.

A variety of maxillary fracture patterns can occur in

severe facial trauma, but classically three patterns,

the Le Fort fractures, are described (Figure 18-4).5

The Le Fort I fracture involves the lower midface

and may be unilateral or bilateral. The fracture line

is located above the level of the teeth but below the

nose. The teeth and hard palate are separated from

the upper portions of the maxilla. The lower portion of the maxilla is mobile. Occasionally, the

lower portion will be fractured at the midline into

two segments.

The Le Fort II (ie, pyramidal) fracture is located at

a higher level than Le Fort I fractures. The fracture line

generally passes through the nasal bone, the lacrimal

bone, the floor of the orbit, the infraorbital margin,

and across the upper portion of the maxillary sinus

and pterygoid plates to the pterygopalatine fossa. The

maxilla is “free floating” in this fracture.
441

Injuries to the Face and Neck

NECK INJURIES

The neck region contains a number of critical

neurological, vascular, and airway structures in a

relatively small space. Blunt and penetrating trauma

to the neck can cause a wide variety of injuries,

ranging from minor to severe to life threatening.

Neck injuries in the military setting carry a 10% to

15% mortality.6 Airway injury, vascular injury, and

cervical spine injury can rapidly lead to death. If

not properly managed, esophageal injuries can lead

to serious infection, sepsis, and death. Quick and

effective medical management can be lifesaving in

some of these casualties.

The neck is commonly divided into three anatomical sections, one above the next.7 Zone I, the

lowest section, is the area behind the clavicles up to

the cricoid cartilage. Zone I contains portions of the

major vessels from the chest as well as portions of

the lung apices, upper mediastinum, trachea,

esophagus, and thoracic duct. This zone is partially

protected by the clavicles. Zone II is bounded by

horizontal planes at the level of the cricoid cartilage

below and the angle of the mandible above. This

section contains portions of the airway, esophagus,

major blood vessels, cranial and peripheral nerves,

cervical spine and spinal cord, and other structures.

Zone II is relatively vulnerable to injury because the

only bony protection is the cervical vertebral column to the rear. Zone III is the section between the

angle of the mandible below and the base of the

skull above. This zone contains many of the same

structures as zone II, but surgical exposure is much

more difficult in this region.

Neck injury can be caused by both blunt and

penetrating trauma. Examples of blunt trauma are

vehicular accidents and falls. Sources of penetrating trauma are gunshots, fragmentation blasts, knife

wounds, and high-speed vehicular accidents.

Casualties with neck injuries require rapid evaluation to assess airway injury or compromise, ventilation, vascular injury, esophageal integrity, and

neurological function. As with other injuries, the

first priority is to ensure that the casualty has a

secure airway and adequate ventilation. The possibility of cervical spine injury must be considered in

every instance. In some cases, urgent intervention

is required to stabilize the casualty. In others, the

casualty can be monitored while injuries are evaluated in more detail and a surgical plan is developed.

Expedient surgical exploration of penetrating neck

injuries is indicated if the medical officer suspects

vascular, airway, esophageal, or neurological injuries, or a missile path that crosses the midline.8

Airway Injuries

Potential injuries to the airway in neck trauma

include crush injuries of the laryngeal structures

and cricoid cartilage; tears, fistulae, lacerations,

and transection of the trachea; bleeding and mucosal edema in the airway; and vocal cord obstrucThe Le Fort III fracture results in complete sepa- a b

ration of the facial bones from their cranial attachments. The fracture line is high in position and

extends across the nasofrontal suture and through

the upper orbits. The main fracture segment is the

entire midface. Le Fort II and III fractures are

commonly associated with intracranial injuries, cribriform plate injuries, dural tears, and cerebrospinal

fluid leaks.

Zygomatic Fractures

Fractures of the zygoma are less severe than

maxillary fractures. However, displaced bony fragments may impinge on the coronoid process of the

mandible and make opening the mouth difficult

and painful. This can complicate airway management. Other signs of zygomatic fracture include

ophthalmological abnormalities, flattening of the

cheek, bony step-off deformity, and ecchymosis.

Fig. 18-4. (a) Anterior view of typical Le Fort I fracture

lines (bottom line), Le Fort II fracture lines (center line),

and Le Fort III fracture lines (top line). (b) Lateral view of

the typical Le Fort fracture lines.
Anesthesia and Perioperative Care of the Combat Casualty

442

tion due to nerve injury or arytenoid dislocation.

The airway can also be compressed and obstructed

by adjacent hematomas and subcutaneous emphysema in the neck.

Airway injuries can rapidly lead to death in

the field before the casualty can be transported to

a medical facility. Casualties with airway injuries may present for emergency treatment in

severe respiratory distress. They can also present

with what appears to be minor respiratory compromise and can, over a period of hours, insidiously

develop airway obstruction from expanding

hematomas or edema. The airway should be secured early if any signs of distress are present. This

topic is discussed more fully in Chapter 3, Airway

Management.

The integrity of the larynx can be disrupted by

crush injuries from blunt trauma or from damage to

the cartilage or supporting structures from penetrating trauma. Blunt trauma can also damage or

collapse the cricoid cartilage and can cause tearing

or total disruption of the cricotracheal junction.

Penetrating trauma can tear, lacerate, or transect

the trachea at any level. If the trachea or laryngeal

structures are damaged, the airway must be secured below the lowest level of the injury. A

tracheostomy can be done on an emergent basis, if

necessary. Cricothyroidotomy is contraindicated if

the cricothyroid area is damaged or if the trachea is

damaged, as the canula could easily be placed into

a false passage. With a tracheostomy, the surgeon

may be able to get below the level of the tracheal

injury and avoid placing the canula into a false

passage. A transected trachea requires rapid surgical exploration and retrieval of the retracted distal

segment. If time allows, casualties with airway

injuries can potentially be intubated using a

fiberoptic technique.

Vascular Injuries

Vascular injuries are common in penetrating neck

trauma9 and relatively uncommon in blunt neck

trauma. Arterial injuries can lead to exsanguination,

cerebral ischemia, and hematomas that can compress the airway. Venous injuries can lead to

exsanguination or air embolism. Rapid exsanguination and loss of large volumes of blood into the

chest can occur if the major vessels in zone I are

disrupted. Fistulae from blood vessels to the airway can lead to massive pulmonary aspiration.

If time allows, preoperative angiography will

help define the extent of the vascular injury. Early

airway control will be needed if the patient has

hemodynamic instability, neurological compromise,

or bleeding into the airway. If the casualty is unstable, then rapid surgical control and resuscitation

will be needed. The anesthesia team and surgical

team must keep each other apprised of the patient’s

condition, ongoing blood loss, adequacy of control

of bleeding, and the status of both blood-component and volume resuscitation.

Intraoperatively, continuous processed electroencephalography is valuable in monitoring for global cerebral ischemia during arterial clamping and

repair. In addition, maintenance of a normal blood

pressure will help maximize cerebral blood flow via

collateral routes when one of the carotid or vertebral arteries is compromised.

There is a potential for air embolism if the internal jugular vein is disrupted. This can be a fatal

complication if massive air aspiration occurs. The

patient should be monitored for onset of air embolism with a precordial stethoscope, continuous respiratory-gas analysis, and precordial Doppler

probe, if available. Transesophageal echocardiography is an extremely sensitive monitor of venous air

embolism. Treatment of venous air embolism, should

it occur, includes head-down positioning of the patient; flooding the surgical field; aspiration of air from

the right atrium with a multiorifice central venous

catheter; discontinuation of nitrous oxide, if it is

being used; and hemodynamic support, if needed.

Nerve Injuries

Neurological structures that can be injured in

neck trauma include the spinal cord, brachial plexus,

phrenic nerves, cranial nerves, and sympathetic

fibers. Spinal cord injuries are discussed below in

the section on cervical spine injuries. Brachial plexus

injuries can result in upper-extremity weakness

and paresthesia. Causalgia is a common late complication of brachial plexus injury. Phrenic nerve

injury leads to paralysis of the hemidiaphragm.

Injury of the vagus nerve or the recurrent laryngeal

nerve can result in vocal cord paralysis, which can

contribute to airway obstruction. Injury of the

vagus nerve or superior laryngeal nerve may abolish sensation above the vocal cords and can blunt

protective airway reflexes.

Esophageal Injuries

Esophageal injuries occur more frequently with

penetrating than with blunt neck trauma. Disruption
443

Injuries to the Face and Neck

of the esophagus can easily lead to infection that

spreads to the mediastinum and becomes life threatening. Fistulae between the esophagus and the trachea, or between the esophagus and the blood vessels,occasionally occur. Esophageal tears and lacerations

require early surgical diagnosis and repair.10

CERVICAL SPINE INJURIES

Injuries to the cervical vertebrae can occur when

soldiers fall from a height, have direct penetrating

trauma to the neck, or suffer head and face injuries

or multiple trauma. The incidence of serious cervical spine injury in patients with major trauma varies from 1% to 3%.11 Because of the potential for

permanent injury to the cervical spinal cord, cervical spine trauma can be devastating. Medical personnel must carefully protect the cervical spine

from the time of their first contact with the soldier

until such time as injuries to the cervical vertebrae

and spinal cord are either ruled out or definitively

stabilized. Spinal cord injury can occur during field

stabilization, transport to the hospital, airway management, or at any other time in the early phases of

care. Initial care requires immobilization of the

neck, control of the airway, assessment of cervical

spine stability, and evaluation of neurological damage. Subsequent care involves restoration of anatomical integrity of the cervical vertebral column if

required, continued protection of the cervical spinal cord, and rehabilitation. Injuries to the cervical

spine and spinal cord are also discussed in Chapter

1, Combat Trauma Overview, and are the subject of

Chapter 16, Neurological Injuries.

Cervical Vertebral Injuries

There are seven vertebrae (C-1 through C-7) in

the neck. They provide support for the skull and

protection for the cervical spinal cord. C-1 and C-2

are unique in structure and function. C-1, the atlas,

consists of anterior and posterior arches and has no

protruding articular processes. It articulates with

the occipital condyles of the skull above and with C2 below. C-2, the axis, has an anterior upward

protrusion called the dens or odontoid process. C2 has downward-protruding articular processes

posteriorly. The dens and the articular surfaces

articulate with C-1 above. C-2 articulates with C-3

via the articular surface of the body anteriorly and

protruding articular processes posteriorly. C-3

through C-7 are similar in structure. Each vertebra

consists of a body anteriorly, articular processes to

the sides, and a spinous process posteriorly. Pedicles

connect the body to the articular processes; laminae

connect the articular processes to the spinous process. C-2 to C-7 articulate with each other via the

posterior articular processes. The bodies of C-2 to

C-7 are linked by intervertebral discs. The cervical

vertebral column is strengthened by numerous ligaments.

The cervical spine is the most mobile and the

least protected portion of the vertebral column, and

is susceptible to injury from blunt and penetrating

trauma. Instability of the cervical spine can result

from fractures of portions of the vertebrae or disruption of the supporting ligaments. Compression

fractures of the vertebral bodies and fracture-dislocations of the articular processes can cause cord

compression and injury. Chin, mandibular, and

zygomatic injuries are more commonly associated

with injuries of the upper cervical spine, whereas

upper-face and scalp injuries are more commonly

associated with injuries of the lower cervical spine.

Cervical Spinal Cord Injuries

In the cervical region, the spinal cord occupies

two thirds of the vertebral canal. Anterior and

posterior nerve roots exit the spinal cord at intervals. The anterior roots have somatic fibers that

control muscle movement, and the posterior roots

have afferent fibers that carry sensory impulses.

Spinal cord trauma can occur directly, as a result

of penetrating injury, or indirectly, from cord compression due to cervical fractures or dislocations.

From 30% to 70% of patients with significant cervical spine injury may have associated spinal cord

injury.12 Compression of the spinal cord leads to

vascular insufficiency, ischemia, edema, and neuronal cell death. Cord injuries can be complete, in

which case no neurological impulses pass through

the level of the injury, or they can be incomplete, in

which case partial neurological deficits are present.

Injuries to the brainstem or the upper cervical spinal cord are often fatal because of interruption of

respiration and other vital functions. The innervation of the diaphragm is at the C-3 to C-5 level.

Thus, injuries to the spinal cord at these levels or

higher lead to respiratory failure. Injuries to the

lower cervical spinal cord can interrupt intercostal

muscle function, which seriously impairs pulmonary function.
Anesthesia and Perioperative Care of the Combat Casualty

444

Injury to the anterior portion of the spinal cord

damages the spinothalamic and corticospinal tracts.

Deficits include paralysis with loss of pain and

temperature sensation. Injury to the posterior spinal cord is less common. Deficits include varying

degrees of sensory loss and impairment of the positional and vibratory senses. In the Brown-Sequard

syndrome, one side of the spinal cord is damaged.

Deficits include motor weakness on the side with

the lesion and pain and temperature sensory insensitivity on the side opposite the lesion. The BrownSequard syndrome can occur with penetrating

trauma and with certain subluxation or dislocation

injuries of the cervical vertebrae.

Spinal cord injury can cause a condition known

as spinal shock. Disruption of the sympathetic

fibers at the cervical cord level results in vasodilation, bradycardia, and hypotension. This condition

occurs early in the injury and lasts several days to

weeks. If spinal cord function does not recover, this

syndrome gives way to autonomic hyperreflexia, a

condition in which hyperresponsive autonomic reflex loops develop in the isolated lower level of the

spinal cord. These conditions greatly complicate

the perioperative management of casualties with

spinal cord injuries.

Because spinal cord injuries are often permanent

and devastating, every effort must be made to identify cervical spine instability and to protect the

spinal cord during medical treatment.

Evaluation of Cervical Spine Injuries

Soldiers with any of the following conditions

need radiological evaluation to rule out cervical

spine injury13:

• multisystem trauma,

• blunt facial or head trauma,

• altered sensorium or neurological deficits,

• serious facial or scalp lacerations,

• fractures above the clavicles,

• traumatic neck pain or tenderness, or

• penetrating neck injuries.

An exception to this policy is patients who are fully

alert, who do not have neck pain or tenderness, and

who do not have other painful injuries that would

mask neck pain. The standard radiological evaluation of the cervical spine consists of three views:

cross-table lateral, anteroposterior, and open-mouth

odontoid. All seven cervical vertebrae must be fully

imaged on the cross-table lateral and anteroposterior

views. Computed tomography views of the cervical

vertebral column should be obtained if the plain

views are inadequate or questionable, or if a neurological deficit is present.13 Computed tomography

is also indicated in patients with high-energy penetrating trauma to the cervical spine.14

Management of Blunt Cervical Spine Injuries

Initial care of soldiers with potential blunt cervical spine injuries should follow ATLS guidelines.

At first contact with such a soldier, medical personnel should immobilize the neck, and, if necessary,

the airway should be stabilized. Some casualties

will require urgent airway intervention. Airway

management must be approached with great caution because the risk of permanently injuring the

cervical spinal cord is ever present. The most common methods of securing the airway in casualties

with potential cervical spine injuries are oral

intubation with cervical spine immobilization and

blind nasal intubation. These techniques and other

airway-management options are discussed later in

this chapter.

Anesthesia providers must be concerned with

more than just securing the airway in casualties

with possible cervical spine injuries: they must carefully protect the cervical spine and the spinal cord

during the perioperative period. The neck must be

maintained in a neutral alignment during transport

and positioning. Protection of the spinal cord also

involves maintaining perfusion pressure and oxygenation. If spinal cord injury has occurred, high-dose

methylprednisolone has been shown15 to be of value

in improving neurological outcome in some patients.

Recovery from spinal cord injury depends on

• the extent of the initial injury,

• prevention of further injury, and

• avoidance of hypoxia and hypotension.

Spinal shock sometimes complicates the care of

casualties with spinal cord injury. It is a syndrome

that can be seen in the acute phase of spinal cord

injury. The sympathetic system is disrupted by the

injury and the casualty develops bradycardia, vasodilation, and hypotension. Profound hypotension

is brought on by blood loss and positional changes.

Fluid loading, atropine, and vasopressors may be

required to treat spinal shock. Patients with spinal

shock quickly develop pulmonary edema in response

to fluid overload. Invasive monitoring can help

guide fluid management in the perioperative period.

Over a period of days to weeks, the syndrome of

spinal shock gives way to a chronic condition known
445

Injuries to the Face and Neck

as autonomic hyperreflexia. This is a syndrome of

hyperreactive autonomic reflexes that sometimes

develops in casualties with cord injuries above the

T-6 level. Unchecked reflexes in the isolated spinal

cord cause dramatic vasoconstriction and hypertension to occur in response to various stimuli.

Autonomic hyperreflexia can be blocked by regional

or general anesthesia and can be treated with potent

vasodilators.

Patients with spinal cord injuries also have problems with temperature regulation. Careful temperature monitoring and meticulous patient warming are needed in the perioperative period.

Casualties with spinal cord injuries quickly develop the potential for a hyperkalemic response to

succinylcholine administration. The rapid increase

in serum potassium that occurs can cause fatal

dysrhythmias. The dramatic potassium release results from a rapid increase in the neural receptors

on the muscle membranes when normal neural tone

is interrupted by spinal cord injury. Succinylcholine should be avoided in patients with spinal cord

injuries more than a few hours old.

Casualties with cervical cord injuries can also

develop respiratory dysfunction. Forced vital capacity is greatly reduced in patients with lower

cervical cord injuries because of loss of intercostal and abdominal muscle function. Aspiration

and pneumonia are common complications.

Careful pulmonary care is required in these patients to minimize serious respiratory complications.

During surgical stabilization of cervical spine

injuries, the anesthesia provider can contribute to

the improved outcome of patients by providing

evoked-potential monitoring. Extension of spinal

cord injury can be prevented in some cases with this

neurological monitor.16

ASSOCIATED INJURIES

Injuries to the face and neck are frequently dramatic in appearance. They can divert the medical

team’s attention away from other associated injuries. The associated injuries, although they are at

times less obvious than face and neck injuries, can

nonetheless be serious and potentially life threatening, and can greatly affect patient outcome and

anesthetic management. Once the airway is secure

and the cervical spine is stabilized, the most serious

of the injuries must be dealt with.

The proximity of the face and neck to the major

vessels and other important structures makes the

possibility of serious associated injuries likely. The

injuries most commonly seen in association with

face and neck trauma are intracranial and ocular.

Neurological Injuries

Most patients with extensive facial injuries have

associated neurological injuries.1 Overt head trauma

may be detected on initial observation and examination of the patient; however, serious intracranial

injury can be present with only minimal external

trauma. During the primary trauma survey, the

patient’s pupillary symmetry and response are assessed and the patient’s level of consciousness is

quickly evaluated.4 The Glasgow coma scale is a

convenient and accepted system for evaluating and

documenting the patient’s level of consciousness

(also see Chapter 1, Combat Trauma Overview, Chapter 3, Airway Management, and Chapter 16, Neurological Injuries). If neurological abnormalities are

detected on initial evaluation or if extensive face

and neck injuries are present, then neurosurgical

consultation should be obtained.17 Examination by

a neurosurgeon and skull radiographs, computed

tomography, and nuclear magnetic imaging are

indicated in most cases.18 If sophisticated imaging

systems are not readily available, which will be

the case in most field environments, then management decisions will need to be based on clinical evaluation. The focus then will be on stabilization and

transfer of the casualty to a medical treatment facility equipped for full neurosurgical evaluation

and care.

Patients with head injury and an altered level of

consciousness, especially those whose Glasgow

coma scale score is lower than 9, are likely to have

increased intracranial pressure. The presence of

elevated intracranial pressure significantly influences the airway-management plan and the perioperative anesthetic management plan. Special monitoring is indicated in these patients. The use of

intracranial pressure monitoring allows the military trauma anesthesiologist to monitor the effects

of anesthetic interventions. The availability of continuous capnography permits precise control of

blood carbon dioxide levels through adjustments in

ventilatory support. Carbon dioxide levels directly

affect intracranial blood flow, which, in turn, influences intracranial pressure. In the postoperative

period, repeated neurological examinations as well

as continued monitoring of intracranial pressure

are of value. If postoperative mechanical ventila-
Anesthesia and Perioperative Care of the Combat Casualty

446

tion is required, continued monitoring of exhaled

carbon dioxide is important.

Ocular Injuries

Eye injuries are common in the military combat

environment. There are many causes, but eye injuries in combat most commonly are the result of

fragmentation blasts from artillery, mortars, or other

munitions. Proper anesthetic management of the

patient with eye injuries is critical: mismanagement

can lead to permanent disability (also see Chapter

17, Eye Injuries).

There are two basic types of eye injuries: penetrating (ie, open) and nonpenetrating. As a rule,

nonpenetrating injuries are less severe than penetrating injuries, but either type can lead to blindness.

Nonpenetrating eye injuries, in which the globe

remains intact, usually present a lesser anestheticmanagement dilemma than penetrating eye injuries,

in which the globe is disrupted. Nonpenetrating eye

injuries include injuries to the eye and orbit and can

be as minor as a corneal abrasion or eyelid

ecchymosis, or as severe as retinal detachment, vitreous hemorrhage, or optic nerve injury. Penetrating

injuries can cause a wide spectrum of damage to the

eye and orbital structures. Eye injuries in which the

globe is fully perforated require careful anesthetic

management to avoid extrusion of intraocular contents and resultant permanent disability.

In managing casualties with eye injuries, the

anesthesia care provider must (a) avoid increased

intraocular pressure and (b) provide a motionless

surgical field for the ophthalmologist. Increased

intraocular pressure in the open eye can lead to

displacement of intraocular contents and permanent eye injury. Intraocular pressure can be increased by the patient’s coughing and straining

during attempts to manage the airway. Succinylcholine also increases intraocular pressure, caused

by the contraction of extraocular muscles as well as

other less-well-defined mechanisms.19

General anesthesia is usually required in ophthalmic trauma surgery. Retrobulbar block, while

perfectly adequate for most routine ophthalmic

surgery, is contraindicated in the presence of an

open eye injury because it can increase intraocular

pressure. The ideal general-anesthesia induction

technique for a patient with a penetrating eye injury

is similar to that for a patient with increased intracranial pressure. A technique should be chosen that

will ensure that the patient is deeply anesthetized

and fully paralyzed before the airway is instrumented. This will minimize the likelihood that

intraocular pressure will be increased. Unless

strongly indicated for other reasons (eg, immediate

airway control), succinylcholine should be avoided

and a nondepolarizing relaxant should be used in

its place. Nondepolarizing relaxants do not increase intraocular pressure.20 During the maintenance phase of the anesthetic, the patient should

continue to remain deeply anesthetized and well

paralyzed to avoid any movement of the eye or any

increase in intraocular pressure during surgery. A

smooth emergence from anesthesia will minimize

the stress on delicate ophthalmic surgical repairs.

Other Injuries

Injuries to structures other than the cervical spine,

eyes, and head or central nervous system can certainly be present in casualties with injuries to the

face and neck (eg, thoracic, intraabdominal, pelvic,

and orthopedic injuries). The presence of multiple

associated injuries complicates management. Casualties with these kinds of injuries require evaluation by appropriate surgical specialists. The care

plan must be individualized for each casualty and

requires careful coordination among all the specialists involved.

AIRWAY MANAGEMENT

As with other medical emergencies, airway management of combat casualties is of prime importance. The airway requires immediate attention;

additional resuscitative efforts are wasted if airway

management is ineffective or delayed. Casualties

with injuries to the face and neck may present with

acute airway obstruction, or they may develop airway obstruction at some point during their care.

The airway can be obstructed by blood, vomitus,

broken teeth or bone fragments, disrupted soft tissue, or other foreign bodies. In addition, the posterior portion of the tongue may fall back and obstruct the airway.21 This can occur as a result of the

decreased muscle tone that can be seen in neurological injury, or it might be secondary to loss of

support of the base of the tongue due to an unstable

fracture of the mandible. Edema and hematomas in

the airway can cause partial or complete airway

obstruction. Laryngeal and tracheal injuries can

distort and block the airway. Laryngeal injuries

may be occult or otherwise appear minimal at the

time of injury, but can progress to cause airway
447

Injuries to the Face and Neck

obstruction over time.22 If tracheal disruption is

present, positive-pressure ventilation may lead to

subcutaneous and mediastinal emphysema, which

can further distort the airway. Neck injuries can

cause edema and hematomas, which can compress

the airway.

Airway management of these casualties is often

complicated by associated injuries that may be

present. Cervical spine injury, intracranial injury,

blood loss, and the risk of aspiration all influence

the way that the airway is managed.

Mask Ventilation

Mask ventilation may be required in emergent

circumstances to stabilize casualties who have face

or neck injuries. The following conditions interfere

with effective mask ventilation by causing an obstruction or otherwise preventing an effective mask seal:

• facial lacerations,

• nasal fractures,

• maxillary fractures,

• mandibular fractures, and

• dental trauma.

If the casualty’s airway is obstructed by the tongue,

then forward displacement of the mandible may

open the airway. Pulling the tongue forward with

gauze, clamps, or sutures are other maneuvers that

may relieve obstruction of the airway. These techniques tend to interfere with mask ventilation, but

if the casualty is making spontaneous respiratory

effort, the relief of obstruction may be all that is

needed to restore adequate ventilation. (Placing the

casualty in a lateral position may also correct the

obstruction, but such movement could potentially

injure the cervical spinal cord if the cervical spine is

unstable.) In many cases, placing an oral airway

device will relieve the obstruction, but blind placement in a casualty with potential intraoral or pharyngeal injury could be harmful and could potentially worsen the obstruction.

Mask ventilation should be considered a temporary technique to stabilize the casualty while provisions are made to obtain more definitive airway

control. During mask ventilation, the patient’s airway remains unprotected and aspiration is always

a risk. Blood and food in the stomach, bleeding in

the airway, and an altered level of consciousness

are factors that are frequently present and that

increase the likelihood of aspiration.

Cricoid pressure in the casualty whose protective airway reflexes are inadequate will normally

prevent passive regurgitation. However, attempts

to block active vomiting with cricoid pressure are

likely to fail and may cause esophageal injury.

Proper positioning of the casualty and rapid, effective suctioning are the best means of dealing with

active vomiting. If the casualty can cooperate, or if

he has a nasogastric or orogastric tube in place, then

a clear antacid solution can be given to neutralize

the stomach acid. Reducing the acidity of stomach

contents will decrease the pulmonary inflammatory response if aspiration does occur.

Tracheal Intubation

Tracheal intubation of casualties with face or

neck injuries can be difficult. The possibility of

cervical spine instability in these patients further

complicates airway management. Intubation alternatives for casualties with possible cervical spine

injuries include the following:

• orotracheal intubation with cervical immobilization,

• blind nasotracheal intubation,

• fiberoptic tracheal intubation,

• lighted stylet orotracheal intubation, and

• retrograde wire tracheal intubation.

Orotracheal intubation under direct laryngoscopic visualization is a technique with which anesthesia providers are quite comfortable. Direct visualization of the airway is valuable in patients with

facial injuries because airway injuries can be assessed. In addition, the risk of esophageal intubation

is reduced. Intubation under direct laryngoscopic

visualization can be dangerous in patients with

cervical spine injuries if the neck is manipulated.

Some authorities23 believe that orotracheal intubation of patients with cervical spine injuries

could damage the spinal cord. Others24,25 are confident that, with meticulous cervical spine immobilization, orotracheal intubation is safe and reliable.

Cervical collars do not provide adequate stabilization for oral intubation.26 The recommended technique for immobilization of the cervical spine is to

have a skilled practitioner apply moderate, manual,

in-line traction and stabilization to the head and

cervical spine.27 Preferably, the surgeon in charge

should provide the in-line traction.4 If that is not

feasible, another appropriately trained member of

the trauma team may apply the traction. The neck

should be maintained in a neutral position throughout the intubation. If orotracheal intubation in a

casualty with a potential cervical spine injury re-
Anesthesia and Perioperative Care of the Combat Casualty

448

quires that the neck be extended, then an alternative

airway-management technique should be selected.

Some authorities28 believe that blind nasotracheal

intubation should be the primary initial intubation

technique for patients with possible cervical spine

injuries. Blind nasal intubation is a simple, rapid

technique that is reasonably reliable. However, it is

difficult to perform successfully in apneic patients,

and it is contraindicated in patients with midface or

basilar skull fractures.29 Because this is a blind technique, it should not be used if the integrity of the

airway has been disrupted. False placement into a

tissue plane may cause airway obstruction. If nasal

intubation is required in a patient with midfacial or

nasal injuries, the nasal airway should be inspected

with a fiberscope prior to intubation. A common

complication of blind nasal intubation is epistaxis.

Blood in the airway complicates subsequent attempts at airway management.

Fiberoptic tracheal intubation is an excellent technique for securing the airway in casualties with

potential cervical spine injuries or with facial injuries.30 The neck is maintained in a neutral position

and the airway is visualized throughout the

intubation. The nasal or the oral route can be used.

The technique is quick and reliable in skilled hands.

In casualties with face and neck trauma, the

fiberoptic technique allows the anesthesia provider to evaluate the integrity of the airway. Drawbacks include equipment expense, impairment by

blood and secretions, the length of setup time required, and the need for training and experience.

For these reasons, fiberoptic intubation is used primarily in the controlled, as opposed to the emergent, setting.

Retrograde wire tracheal intubation is useful in

some patients with facial or possible cervical spine

injuries.31 A catheter is placed percutaneously

through the cricothyroid membrane, angling cephalad. A flexible guide wire is inserted through the

catheter and advanced until it can be pulled out of

the mouth. A tracheal tube exchanger, or a substitute such as a section of a nasogastric tube, is

threaded over the wire and into the mouth. An

endotracheal tube is then inserted over the tube

exchanger. The wire is pulled out from the mouth

end and the endotracheal tube is advanced off the

tube exchanger and down the trachea. A variation

of this technique is to use a long guide wire and

thread it through the suction port of a fiberoptic

bronchoscope.32 The bronchoscope is advanced

blindly over the guide wire and is directed by the

guide wire into the trachea. The wire is then removed and the bronchoscope is advanced to the

carina. The endotracheal tube that was placed over

the fiberoptic bundle is then advanced into the

airway. The retrograde wire technique is quick and

reliable. Its primary advantage is that it can be

performed even if the airway contains blood or

secretions.

Lighted stylet tracheal intubation is quick and

reliable in skilled hands,33 although this is a blind

technique and should not be used in casualties who

may have airway injuries. The casualty’s neck is

maintained in a neutral position during the

intubation. The technique involves placing the

endotracheal tube over a malleable lighted stylet.

The stylet is bent to approximately a right angle at

the level of the endotracheal tube cuff. The casualty’s

tongue or mandible is displaced forward and the

stylet is directed blindly toward the glottis. The

anesthesia provider observes the neck and watches

for a bright, midline transillumination at the level of

the lower portion of the thyroid cartilage. The

endotracheal tube is then advanced off the stylet

and down the trachea. The success rate for lighted

stylet intubation is related to the experience and

training of the practitioner.

Tracheal intubation of the unconscious patient

can generally be accomplished without any anesthetic agents. Intubation of the conscious patient

will normally require some form of topical or general anesthesia. Topical anesthesia puts the patient

at risk for aspiration of gastric contents. If topical

anesthesia is incomplete, airway stimulation during intubation may induce vomiting or may cause

the patient to move suddenly. Induction of general

anesthesia also abolishes protective airway reflexes

and can cause severe hemodynamic instability in

casualties who are hypovolemic from blood loss.

The anesthesia provider must select the technique

that provides the best balance between the intubating

conditions and the patient’s stability. The subject is

discussed in greater detail in Chapter 3, Airway

Management.

Transtracheal Jet Ventilation

Transtracheal jet ventilation is a temporizing technique that stabilizes the patient and allows time for

the practitioner to secure longer-term control of the

airway. The technique involves placing a large

intravenous catheter, such as a 14-gauge catheter,

percutaneously through the neck into the upper

trachea. This is connected to a high-pressure oxygen source (50 psi) with a tubing system that has an
449

Injuries to the Face and Neck

adjustable pressure regulator and a manual valve.

The oxygen source can be a wall source, an oxygen

tank, or the flush-valve output of the anesthesia

machine. The breathing circuit of the anesthesia

machine is not an acceptable gas source for

transtracheal jet ventilation because the driving

pressure is too low. Bag-valve systems are unacceptable for the same reason. The specific components that make up an effective transtracheal jet

ventilation system are well described in the literature.34 To be useful in emergencies, the system must

available and already connected to an oxygen source.

The anesthesia provider provides manual ventilation for the patient, while also adjusting the driving pressure and watching the patient’s chest rise

and fall with each breath. The advantages of

transtracheal jet ventilation are that it is fast, effective, and lifesaving. The disadvantages are the risk

of bleeding from catheter placement, and the risk of

pneumothorax if the driving pressure is too high or

if the tracheal outlet is obstructed. Improper placement of the catheter may lead to subcutaneous

emphysema. Inadequate alveolar ventilation will

result in hypercarbia.

Cricothyroidotomy

In some casualties with face or neck injuries,

adequate mask ventilation may be impossible, and

tracheal intubation may be dangerous or unsuccessful. In the emergent situation, cricothyroidotomy is a rapid and effective means of airway

control. Since cricothyroidotomy has a significant

complication rate in the emergency setting,35 it

should be performed only when the airway cannot

be secured by other methods.

If the anatomical landmarks are not distorted, a

cricothyroidotomy incision can quickly be made

between the thyroid cartilage and the cricoid cartilage. A small, cuffed endotracheal tube, or any

makeshift stent, can be placed through the incision

into the airway.

Most anesthesia providers prefer cricothyroidotomy to tracheostomy in emergent situations because

• the risk of bleeding is reduced,

• surgical access is quicker, and

• anatomical landmarks are more reliable.

Tracheostomy

Tracheostomy may be performed as the initial

airway-management technique in selected casualties with face and neck injuries. If the casualty has

(a) severe facial injuries that preclude safe or successful orotracheal or nasotracheal intubation and

(b) injury to the cricothyroid region of the neck that

distorts the anatomical landmarks, then emergent

tracheostomy may be the best option. Tracheostomy

may also be required if the cricothyroid region of

the airway or the uppermost portion of the trachea

is disrupted. In these cases, tracheostomy allows

access to the airway below the area of injury. In

some patients with specific combinations of facial

fractures, tracheostomy may be required so that the

surgery can be completed. If time allows and the

patient is stable, awake tracheostomy at the beginning of the surgery may be safer than the anesthesia

provider’s attempting to perform orotracheal or

nasotracheal intubation in the presence of multiple facial fractures and a potentially unstable

cervical spine. In most cases where postoperative

tracheostomy will be necessary, however, it is best

to wait until near the conclusion of the surgery to

perform the tracheostomy.

In the management of patients with face and neck

trauma, airway stabilization takes top priority.

Other problems that require early attention (and

are often a result of associated injuries) are hemorrhage and hypovolemic shock. Stabilization of these

patients requires early and continued involvement

of the anesthesia team, as well as the coordinated

efforts of multiple surgical specialty teams when

associated injuries are present.18 Although the dramatic appearance of face and neck injuries may

divert the attention of the medical personnel away

from the casualty’s other injuries, expedient care of

the associated injuries may initially take precedence

over repair of the face and neck injuries. The individual surgical teams may have distorted views of

the priorities of medical care, and communication

among the surgical teams—including the anesthesia team—is crucial to assure that proper priorities

are maintained and that care proceeds appropriately.

The anesthesia team must seek active involvement in

the preparation and planning for surgery to ensure

that the associated injuries are identified preoperatively, and that the patient is maximally resuscitated and stabilized preoperatively.

PERIOPERATIVE ANESTHETIC MANAGEMENT
Anesthesia and Perioperative Care of the Combat Casualty

450

Numerous associated problems that can complicate perioperative anesthetic management may be

present in patients with face and neck trauma:

• an inadequate airway,

• hemorrhage,

• intracranial injury,

• spinal injury,

• pulmonary contusion,

• pulmonary aspiration,

• pneumothorax,

• cardiac contusion,

• cardiac tamponade,

• intraabdominal injury, and

• renal injury.

Some problems, such as pneumothorax, cardiac

tamponade, and external hemorrhage, should be

corrected before the administration of general

anesthesia, if at all possible. Other problems,

such as intraabdominal injury, can be stabilized

under general anesthesia, whereas problems like

increased intracranial pressure, aspiration pneumonitis, and acute renal failure will have a significant impact on anesthetic management and will

continue to require attention throughout the perioperative period. Safe anesthetic management depends on the ability to monitor affected organ systems during the resuscitative and operative phases

of treatment.18 Physiological monitoring of the patient with face and neck trauma may include such

modalities as central venous lines, arterial lines,

Foley catheters, repeated blood analysis, and possibly intracranial pressure monitoring, in addition to

the usual anesthesia monitoring. Appropriate

perioperative anesthesia monitoring may help

identify ongoing renal, respiratory, and neurological injury.

Local and Regional Anesthesia

Not all face and neck trauma patients require

general anesthesia. Patients with multiple injuries

and patients with severe maxillofacial injuries will

normally require general anesthesia, but patients

with isolated and less-severe injuries may do well

with regional and local anesthesia. Limited facial

soft-tissue injuries can usually be repaired with

local anesthesia alone. In fact, the use of epinephrine-containing local anesthetic will provide improved hemostasis compared with that provided

by regional or general anesthesia. Local and regional anesthesia, however, can induce temporary

paralysis of the facial nerve, which may interfere

with the diagnosis of facial nerve injury. Regional

anesthesia can be used for selected areas of the face

and neck.

General Anesthesia

Patients who require extensive or lengthy procedures and patients who are uncooperative will need

general anesthesia.36 Anesthetic techniques and

monitoring are influenced primarily by the associated injuries that are present. Anesthetic induction

and intubation require careful evaluation of the

airway and consideration of the side effects of the

induction agents. Anesthetic induction is greatly

simplified if the casualty’s airway was intubated

during the initial stabilization and resuscitation.

Induction agents can then be selected and titrated to

produce minimal adverse effects on the associated

injured organ systems. If intubation is required in

the operating room, then induction agents and techniques must be selected that provide maximally

safe intubating conditions while at the same time

minimize risk to injured organ systems. All factors

must be considered, and each situation must be

individualized.

The safest induction technique for patients at risk

for aspiration, which includes most trauma victims,

is usually a rapid-sequence induction using a hypnotic agent such as ketamine or sodium thiopental

along with succinylcholine. However, in patients

with possible cervical spine injury, which, again,

includes many trauma patients, awake intubation

with cervical spine immobilization is generally indicated, if time and conditions allow. Patients with

increased intracranial pressure and patients with

open eye injuries should have a slow, controlled,

and complete induction of anesthesia with sodium

thiopental or a similar hypnotic agent, a narcotic

agent, and a nondepolarizing muscle relaxant prior

to intubation of the airway. This technique minimizes the likelihood of a dangerous increase in

intracranial pressure or intraocular pressure at the

start of anesthesia.

Patients with severe hypovolemia from acute blood

loss may not tolerate standard anesthetic-induction

techniques. Severe hypotension or cardiac arrest may

occur if the patient is given a hypnotic induction such

as ketamine, which causes cardiac depression, or

sodium thiopental, which causes sympathetic and

cardiac depression. The safest induction technique

for these patients will generally be scopolamine and

a muscle relaxant alone.
451

Injuries to the Face and Neck

No single induction technique is suitable for all

trauma situations. Often, the medical officer will be

confronted with a combination of injuries and conditions that make choosing the best anesthetic-induction technique difficult (eg, a patient with a

head injury and a full stomach, a patient with an

open eye injury and a displaced mandibular fracture, and an uncooperative patient with bleeding

and possible cervical spine injury). In scenarios

such as these, the anesthesia provider must first

decide which conditions are of overriding importance and then select the most appropriate airwaymanagement technique and anesthetic plan for those

conditions. Careful clinical assessment is required

for every case.

Intraoperative Airway Management

Completion of the initial intubation does not

mean that the airway can then be ignored. Accidental extubation can easily occur when maxillofacial

surgical procedures are in progress. It may be

difficult to secure an orotracheal or nasotracheal

tube in patients with facial injuries due to tissue

disruption and surgical cleansing. Suturing the

tracheal tube in place, monitoring the progress of

surgery, communicating with the surgeons, assisting with head positioning, and continuously monitoring the patient’s ventilation will all help to decrease the risk of accidental extubation.

Both the specific injuries and the specific surgical

procedures planned have an impact on airway management. Orotracheal intubation is generally the

preferred method for initial intubation, but some

surgical procedures (ie, procedures requiring

intermaxillary fixation) cannot be completed with

an orotracheal tube in place. If intermaxillary fixation is required, then orotracheal intubation must

be converted either to a nasotracheal placement or

to a tracheostomy. Nasotracheal intubation is acceptable in patients who do not have nasal fractures, but if nasal fractures are present in conjunction with other fractures necessitating intermaxillary

wiring, then a tracheostomy is likely to be needed.

Tracheostomy in casualties with face and neck injuries is indicated18 in patients

• who have significant intracranial injuries

that require intermaxillary fixation;

• who have nasal fractures combined with

maxillary or mandibular fractures that require intermaxillary fixation;

• who have significant pulmonary injuries or

flail chest, and who also require intermaxillary fixation;

• whose massive soft-tissue swelling may interfere with reintubation;

• who were intubated emergently via a

cricothyroidotomy; and

• who have injuries to the laryngeal or

cricothyroid region.

The placement of a tracheostomy tube does not

guarantee that the airway is secure. The tracheostomy tube can easily become dislodged and, if the

tracheostomy was recently performed, emergent

replacement of the tracheostomy tube may cause

the tube tip to be placed into a blind tract between

tissue planes. Placing “stay” sutures during the

tracheostomy procedure will aid in (a) identifying

the appropriate tissue planes and (b) replacing the

tracheostomy tube if the tube becomes dislodged

before the tracheostomy site has healed. An armored tube, sutured in place, may be more secure

intraoperatively than a standard tracheostomy tube.

Postoperative Airway Management

Patients who are emerging from anesthesia and

are recovering from surgical repair of their face and

neck injuries require special attention. If the patient

is to be extubated at the conclusion of the surgical

procedure, airway protection must be assured.

Caution is required in the patient with intermaxillary

wiring. Intact airway reflexes must be present,

although that alone does not guarantee that aspiration will not occur. Aspiration in the presence of

intermaxillary wiring can easily be fatal.37 Attention must focus on reducing the risk of emesis and

rapidly dealing with it when it occurs. Evacuating

gastric contents with a suction tube and giving an

antiemetic agent prior to extubation will help. Wire

cutters must be immediately available at the bedside and the specific locations of the wires to be cut

should be made clear to personnel caring for the

patient.

Even if the jaws are not wired, other problems

can occur with extubation. If significant soft-tissue

trauma has occurred, postoperative edema or

hematomas may lead to progressive airway obstruction after extubation. If the patient remains

intubated postoperatively, accidental extubation in

an uncontrolled environment can lead to disaster.

Vigilance must be maintained throughout the

perioperative period well into the recovery period

in patients with face and neck injuries.
Anesthesia and Perioperative Care of the Combat Casualty

452

SUMMARY

Casualties with face and neck injuries present

challenging problems to the anesthesiologist. Airway management can be complicated. Serious

associated injuries, especially head injuries, are

often present and can have a significant impact

on anesthetic care. Initial management should follow published ATLS guidelines. Securing the airway, protecting the cervical spine, and providing

ventilation and controlling hemorrhage as needed

are the top priorities. Subsequent management

must be carefully planned and prioritized. This

requires the coordinated effort of the anesthesia

team and the various surgical subspecialty teams

involved.

REFERENCES

1. Grande CM, Wyman CI, Bernhard WN. Perioperative anesthetic management of maxillofacial and ocular

trauma: Injuries of the craniofacial complex. In: Stene JK, Grande CM, eds. Trauma Anesthesia. Baltimore, Md:

Williams & Wilkins; 1991: 266–285.

2. Bellamy RF. Unpublished analysis of the Wound Data and Munitions Effectiveness Team database. Personal

communication, September 1993.

3. Bellamy RF, Zajtchuk R. The weapons of conventional land warfare. In: Bellamy RF, Zajtchuk R, eds. Conventional Warfare: Ballistic, Blast, and Burn Injuries. Part 1, Vol 5. In: Zajtchuk R, Jenkins DP, Bellamy RF, eds. Textbook

of Military Medicine. Washington, DC: US Department of Army, Office of The Surgeon General, and Borden

Institute; 1991: Chap 1.

4. Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians:

Instructor Manual. 5th ed. Chicago, Ill: American College of Surgeons; 1993.

5. Le Fort R. Etude experimentale sur les fractures de la machoire superieure. Rev Chir. 1901;23:208–227.

6. McSwain NE. Penetrating neck wounds: Major advances in the 1980’s. In: Maull KI, Cleveland HC, Strauch GO,

Wolferth CC, eds. Advances in Trauma. Chicago, Ill: Yearbook Medical Publishers; 1986: 135–140.

7. Ordog GJ, Albin D, Wasserberger J, et al. 110 bullet wounds to the neck. J Trauma. 1985;25:238–241.

8. Capan LM, Miller SM, Turndorf H. Management of neck injuries. In: Capan LM, Miller SM, Turndorf H, eds.

Trauma Anesthesia and Intensive Care. Philadelphia, Pa: JB Lippincott; 1991: 409–446.

9. Ayuyao AM, Kaledzi YL, Parsa MH, Freeman HP. Penetrating neck wounds: Mandatory versus selective

exploration. Ann Surg. 1985;202:563–566.

10. Richardson JD, Martin LF, Borzotta AP, Polk HC. Unifying concepts in treatment of esophageal leaks. Am J Surg.

1985;149:157–160.

11. Kreipke DL, Gillespie KR, McCarthy MC, Mail JT, Lappas JC, Broadie TA. Reliability of indications for cervical

spine films in trauma patients. J Trauma. 1989;29:1438–1439.

12. Guthkelch AN, Fleischer A. Patterns of cervical spine injury and their associated lesions. West J Med. 1987;147:428–431.

13. Kellman R. The cervical spine in maxillofacial trauma. Otolaryngol Clin North Am. 1991;24:1–13.

14. Hastings RH, Marks JD. Airway management for trauma patients with potential cervical spine injuries. Anesth

Analg. 1991;73:471–482.

15. Bracken MB, Shepard MJ, Collins WF, et al. Second National Acute Spinal Cord Injury Study. A randomized,

controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. N Engl J Med.

1990;322:1405–1411.
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16. Rose DD, O’Hara CA, Fossum SR, Hanowell LH. Cervical spine injury: Perioperative patient care. AORN J.

1993;57:830–850.

17. Martin SH. Injury of the head and cervical spine. Otolaryngol Clin North Am. 1976;9:403–423.

18. Manson PN, Saunders JR. Anesthesia in head and neck surgery: Head and neck cancer surgery and maxillofacial

trauma. Clin Plast Surg. 1985;12:115–122.

19. Wislicki L, Factors affecting intraocular pressure. Proc R Soc Med. 1977;70:372–374.

20. Calobrisi B, Lebowitz P. Muscle relaxants and the open globe. Int Anesthesiol Clin. 1990;28:83–85.

21. Strate RG, Boies LR. The emergency management of trauma. Otolaryngol Clin North Am. 1976;9:315–330.

22. Huff JS, Magielski JE. Surgical treatment of laryngeal injuries. Otolaryngol Clin North Am. 1976;9:393–401.

23. Bivins HG, Ford S, Bezmalinovic Z. The effect of axial traction during orotracheal intubation of the trauma

victim with an unstable cervical spine. Ann Emerg Med. 1988;17:25–29.

24. Scannell G, Waxman K, Tominaga G, Barker S, Annas C. Orotracheal intubation in trauma patients with cervical

fractures. Arch Surg. 1993;128:903–906.

25. Walls RN. Airway management. Emerg Med Clin North Am. 1993;11:53–60.

26. Aprahamian C, Thompson BM, Finger WA, et al. Experimental cervical spine injury model: Evaluation of airway

management and splinting techniques. Ann Emerg Med. 1984;13:584–587.

27. Wood PR, Lawler PG. Managing the airway in cervical spine injury: A review of the advanced trauma life

support protocol. Anaesthesia. 1992;47:792–797.

28. Jorden RC, Rosen P. Airway management in the acutely injured. In: Moore EE, Eisman B, VanWay EW, eds.

Critical Decision in Trauma. St. Louis, Mo: CV Mosby; 1984: 30–35.

29. Rosenbaum P. Anesthesia for eye, head, and neck surgery. In: Firestone LL, Lebowitz PW, Cook CE, eds. Clinical

Anesthesia Procedures of the Massachusetts General Hospital. Boston, Mass: Little, Brown; 1988: 346–365.

30. Ovassapian A, Dykes MH. The role of fiberoptic endoscopy for airway management. Semin Anesth. 1987;6:93–104.

31. Barriot P, Riou B. Retrograde technique for tracheal intubation in trauma patients. Crit Care Med. 1988;16:712–713.

32. Gupta B, McDonald JS, Brooks JH, Mendenhall J. Oral fiberoptic intubation over a retrograde wire. Anesth Analg.

1989;68:517–519.

33. Ellis DG, Stewart RD, Kaplan RM, et al. Success rates of blind orotracheal intubation using a transillumination

technique with a lighted stylet. Ann Emerg Med. 1986;15:138–142.

34. Benumof JL, Scheller MS. The importance of transtracheal ventilation in the management of the difficult airway.

Anesthesiology. 1989;71:769–778.

35. McGill J, Clinton JE, Ruiz E. Cricothyrotomy in the emergency department. Ann Emerg Med. 1982;11:361–364.

36. Dickinson JT, Jaquiss GW, Thompson JN. Soft tissue trauma. Otolaryngol Clin North Am. 1976;9:331–360.

37. Sims J, Giesecke AH. Airway management. In: Giesecke AH, ed. Anesthesia for the Surgery of Trauma. Philadelphia, Pa: FA Davis; 1976: 71–78.
Thoracic Injuries

455

LAWRENCE L. YEE, M.D.*; ALEXANDER S. RUBIN, M.D.†; AND RONALD F. BELLAMY, M.D.‡

*Formerly, Major, Medical Corps, U.S. Army; Staff Anesthesiologist, Walter Reed Army Medical Center, Washington, D. C. 20307-5001;

currently, Staff Anesthesiologist, O’Connor Hospital, 2105 Forest Avenue, San Jose, California 95128

†Formerly, Major, Medical Corps, U.S. Army; Staff Anesthesiologist, Walter Reed Army Medical Center, Washington, D. C. 20307-5001;

currently, Staff Anesthesiologist, Frederick Memorial Hospital, Frederick, Maryland 21702

‡Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001

THORACIC INJURIES

Chapter 19

INTRODUCTION

TYPES OF INJURY

Penetrating Missiles

Blunt and Blast Injuries

OVERVIEW OF COMBAT THORACIC TRAUMA

GENERAL PRINCIPLES OF MANAGEMENT

Indications for Thoracotomy

Preoperative Evaluation and Preparation

Monitoring

Induction of Anesthesia

Maintenance of Anesthesia

Positioning for Operation

Postoperative Care

DIAGNOSIS AND MANAGEMENT OF SPECIFIC INJURIES

Rib Fractures

Flail Chest

Sucking Chest Wound

Acute Traumatic Hemothorax

Cardiac Tamponade

Cardiac Contusions

Cardiac Rupture

Injuries to the Coronary Arteries

Injuries to the Great Vessels

Pneumothorax

Tracheal and Bronchial Injuries

Parenchymal Lung Lacerations

Traumatic Rupture of the Diaphragm

SUMMARY
Anesthesia and Perioperative Care of the Combat Casualty

456

INTRODUCTION

The casualty suffering thoracic trauma usually

poses a lesser challenge to the military trauma

anesthesiologist than might be supposed. As we

discussed in Chapter 1, Combat Trauma Overview, the reasons for this are simple: (1) most

casualties who are wounded in the chest die on

the battlefield, and (2) only a minority of those

who reach a medical treatment facility alive require a formal thoracotomy. Most survivors require only the insertion of a chest tube. Thus,

thoracic trauma in combat casualties has some of

the all-or-none characteristics of an airplane

crash: the victim is either killed outright or has a

injury that is treatable by simple interventions.

Nevertheless, there are exceptions (eg, the casualty who suddenly exsanguinates when a mediastinal hematoma ruptures, the casualty whose

tracheobronchial tree is filling with blood, the

casualty who suddenly develops massive arterial air embolism when mechanical ventilation is

started) that can push even the most competent

anesthesiologists to their limits.

Thoracic trauma can be the result of one or more

of the four basic mechanisms of injury: penetrating

(ballistic), blunt, blast, and thermal. Thermal injury

resulting from the inhalation of hot, poisonous gases

is an important cause of combat mortality and morbidity in the navy and among soldiers who crew

armored fighting vehicles. Inhalation injury is discussed in Chapter 22, Burn Injuries; therefore, it

will not be further discussed in this chapter.

Penetrating missiles have been far and away the

major source of thoracic trauma in combat casualties, as seen in Table 19-1, which presents data from

two countries and two wars. The data from the U.S.

Army in the Vietnam War covers a 14-month period

(September 1968–November 1969) at the 24th Evacuation Hospital.1

 During this interval, the hospital

served as a specialty center for neurological, head

and neck, and thoracic casualties. Data from the

Rambam Medical Center covers the period 6 to 29

June 1982 (during the military operation in Lebanon that the Israelis call Peace in Galilee).2

Because penetrating trauma is the cause of the

overwhelming majority of combat casualties with

thoracic injuries, and because it is generally agreed

that missile wounds are distributed randomly, the

overall prevalence of thoracic trauma should approximate the fraction of the body surface area that

overlies the thorax: about 16 in 100. Most casualties

with thoracic trauma are killed; therefore, the actual

percentage of the casualty population who will require treatment for thoracic trauma will be somewhat

smaller and usually ranges between 5% and 10%.3

Penetrating Missiles

The nature of the medical problems caused by

penetrating missiles, whether they are bullets from

small arms or fragments from explosive munitions,

is due to three factors:

1. the function of the organ or organs struck,

2. the physical characteristics of the missile,

and

3. the biophysics of the interaction between

the missile and the tissue that is struck.

It should be readily apparent that the first factor—the nature of the organ hit—is of paramount

importance in determining the medical outcome of

a ballistic injury. A missile wound of the brainstem

is likely to be much more serious than a hit made by

a similar missile to the little toe. Unfortunately, the

thoracic cavity has more than its share of organs—

the heart, great vessels, and lungs—the injury of

which will be immediately catastrophic.

The second factor—the physical characteristics

of the missile—is usually assessed in terms of kinetic energy (calculated as 1⁄2MV2, where M represents the projectile’s mass and V its velocity). Tissue destruction caused by a ballistic injury is related

in a general sense to the kinetic energy transferred

to the target tissue such that

1⁄2M(Vent – Vext)2

where Vent and Vext represent the velocity of the

missile when it enters and exits the body, respectively. When the missile does not exit but stops

within the body, the kinetic energy transferred

equals 1⁄2MVent

2. Fragments usually do not exit

from the body, while bullets, unless they deform or

fragment, frequently cause perforating wounds.

Bullets that fragment (ie, rounds fired from the

M16 series of assault rifles) or deform (ie, many

TYPES OF INJURY
Thoracic Injuries

457

TABLE 19-1

ETIOLOGY OF THORACIC TRAUMA

24th Evacuation

Hospital Rambam

US Army, Medical Center

Vietnam1 Haifa, Israel2

energy transfer. The density of the tissue is another

determinant of the projectile–target interaction. The

more dense the tissue, the more complete the energy transfer. Thus, projectile energy transfer is

maximal in bone but minimal in the least-dense

body tissue, the lung. (A more complete discussion of the biophysics of wound ballistics can be

found in the Textbook of Military Medicine volume

Conventional Warfare: Ballistic, Blast, and Burn Injuries.)4

Wound ballistics as it applies to the thorax is best

summarized in the official history of thoracic surgery in World War II:

[H]igh-velocity missiles that traverse the pulmonary tissue therefore often cause surprisingly little

pulmonary damage. The high immediate lethality

of high-velocity wounds of the chest is apparently

directly related to the percentage chance of damage

to vital structures, particularly the heart and great

vessels. If the high-velocity missile does not inflict

a mortal wound, then it often traverses the chest

with considerably less damage to the thoracic contents than is caused by a low-velocity shell

fragment.5(p59)

Blunt and Blast Injuries

In the field, nonpenetrating injuries to the chest

are caused either by forceful contact with a blunt

object or by blast overpressure. Blunt chest trauma

such as may occur in motor vehicle accidents results

from gross compression of the thorax, which may

cause rib fractures and a variable degree of displacement of intrathoracic viscera such as the heart.

In extreme circumstances, the heart may be so displaced that stretch-and-shear strain affecting the

proximal descending aorta may cause it to rupture.

With blunt trauma, but not with blast injury, the

more serious the injury, the greater the likelihood of

rib fractures. Fractures of the upper five ribs are

usually associated with the most serious, and often

occult, injuries.

The exact mechanisms that produce visceral injury within the thoracic cavity following blunt and

blast injury are poorly understood, but it is no

longer thought that acceleration–deceleration of the

body is an important mechanism per se. Extensive

experimental studies using living animals and human cadavers indicate that the probability of injury

can best be understood in terms of (a) the magnitude of compression of the thorax and (b) the velocity at which the compression occurs (Figure 19-1).6,7

When compression is applied slowly (< 1 m/s; eg,

in vigorous closed-chest cardiopulmonary resuscitaTotal Casualties 7,500 938

Chest Trauma 900* 64

Intrathoracic Injury 547 63

Fragment 443 41

Bullet 76 7†

Blunt 28 6‡

Blast 6§

*Including superficial missile wounds as well as blunt trauma to

the chest wall but without any intrathoracic component

†There were, in addition, two casualties with both bullet and

fragment wounds

‡There was a seventh casualty with both fragment and blunt

thoracic trauma

§All six casualties with pulmonary blast injury also had fragment wounds of the thorax

Data sources: (1) McNamara JJ, Messersmith JK, Dunn RA,

Molot MD, Stremple JF. Thoracic injuries in combat casualties in

Vietnam. Ann Thor Surg. 1970;10:389–401. (2) Rosenblatt M,

Lemer M, Best LA, Peleg H. Thoracic wounds in Israeli battle

casualties during the 1982 evacuation of wounded from Lebanon. J Trauma. 1985;25:350–354.

commonly available bullets used by civilian hunters and law-enforcement agencies) typically are

associated with much greater energy transfer than

occurs with intact bullets that cause perforating

wounds.

A second important physical characteristic is the

shape of the projectile. Streamlined bullets can pass

through tissue with little reduction in velocity, while

irregular fragments from explosive munitions slow

rapidly and, therefore, can transfer a much greater

fraction of their kinetic energy—with a corresponding increase in the potential for tissue damage.

The third factor determining the medical consequences of ballistic injury has to do with the interaction of the projectile and the tissue along its pathway. Obviously, the longer the wound tract, the

more damage that is likely to occur. This is true

because (a) the bullet passes through more tissue,

and (b) it is more likely that the bullet will destabilize (either yaw [ie, the long axis of the bullet deviates from the direction of flight] or tumble [ie,

the bullet flips end over end]), greatly increasing
Anesthesia and Perioperative Care of the Combat Casualty

458

 

tion), a decrease in the thoracic anteroposterior

diameter of at least one third must occur before

there is a high risk of damage to internal viscera.

However, when compression occurs at a faster velocity (> 3 m/s), the same injury can occur with

much less compression. When compression is applied very slowly, the viscera have time to adjust to

the distortion produced by their displacement. With

more rapid compression, however, this compensation

is impaired because it involves a time-dependent

variable: namely, the internal displacement of layer

upon layer of tissue as they slide over one another.

The sliding is resisted by the inherent viscosity of

the tissue much as a the viscosity of a flowing liquid

causes hydraulic resistance. When the sliding cannot keep up with the velocity of compression, shearing forces arise that cause tissue laceration, rupture,

or fractures. Such trauma, which results from a

mechanical process that is determined by both the

velocity of the compression and the viscoelasticity

of the tissue, is known as a viscous injury.

Blast injury may be thought of as occupying the

opposite end of the compression–velocity continuum depicted in Figure 19-1. With blast injury,

the compression causes a tiny displacement (measured in a fraction of a millimeter) that occurs at a

speed approaching that of sound. Blast overpressure is especially likely to injure very light, feebly

supported structures such as the alveolar capillaries and tympanic membranes.

Fig. 19-1. In this depiction of the relation between the

amount and the speed of compression, the curved line

indicates a constant probability of the occurrence of a

thoracic injury of a specified lethality. The magnitude of

compression is given as the percentage of the anteroposterior

diameter of the thorax. Data sources: (1) Viano DC, Lau IA.

A viscous tolerance criterion for soft tissue injury assessment. J Biomechanics. 1988;21(5):387–399. (2) Viano DC.

Live fire testing: Assessing blunt impact and acceleration

injury vulnerabilities. Milit Med. 1991;156:589–595.

OVERVIEW OF COMBAT THORACIC TRAUMA

As seen in reports from three recent wars (the

experience of the U.S. Army’s 24th Evacuation Hospital in Vietnam1

; Rambam Medical Center in Haifa,

Israel2; and the Basrah, Iraq, Teaching Hospital in a

6-month period in 1981 during the Iran–Iraq War3),

the most common thoracic clinical problems were

combined hemothorax and pneumothorax, hemothorax, pneumothorax, pulmonary contusion, cardiac tamponade, pulmonary hematoma, rib or sternal fractures or both, perforation of the diaphragm,

and laceration of the heart or great vessels (Table

19-2). These data clearly show that the most common medical treatment problems—collections of

blood and air within the pleural space—are the

result of pulmonary lacerations. It is important to

recognize that the thoracic injury is unlikely to be

the only injury present: 85% of the casualties in the

24th Evacuation Hospital report1 and 80% of the casualties reported from Rambam2 had one or more additional injuries involving another part of the body.

The specific nature of the medical interventions

required to treat combat casualties with thoracic

injuries is shown in Table 19-3. It is apparent that

only a minority of thoracic casualties required a

formal thoracotomy.

When treating a casualty with a thoracic injury,

the military trauma anesthesiologist is much more

likely to provide anesthesia for a major operation in

some other body part than for an operation on the

thorax. Published series, with the exception of the

work of one surgeon in Lebanon (which is discussed below), indicate that a formal thoracotomy

is needed in only about 10% to 20% of casualties

with thoracic injuries who reach a military hospital

alive.8 In most thoracic casualties, the interventions

required for the treatment of the thoracic injury

consist of inserting a chest tube and providing local

care to the wounds of entrance and exit. However,

military trauma anesthesiologists should be aware

that some thoracic surgeons perform what is really

Magnitude of Compression

Compression Injury

Viscous Injury

Blast Injury

1

0

10 100

Velocity of Compression (m/s)

35%
Thoracic Injuries

459

TABLE 19-2

DIAGNOSIS OF THORACIC CASUALTIES

24th Evac. Hospital Rambam Medical Center Basrah Teaching

Diagnosis US Army, Vietnam1 Haifa, Israel2 Hospital, Iraq3

Combined hemo- and pneumothorax 230 15

Hemothorax 199 9 81

Pneumothorax 100 13 37

Pulmonary contusion 99 5 20

Cardiac tamponade 7 1 4

Pulmonary hematoma 15

Rib/sternal fractures 14 12*

Diaphragmatic perforation 17

Heart or great-vessel laceration 4

*Listed as flail chest

Data sources: (1) McNamara JJ, Messersmith JK, Dunn RA, Molot MD, Stremple JF. Thoracic injuries in combat casualties in Vietnam.

Ann Thor Surg. 1970;10:389–401. (2) Rosenblatt M, Lemer M, Best LA, Peleg H. Thoracic wounds in Israeli battle casualties during

the 1982 evacuation of wounded from Lebanon. J Trauma. 1985;25:350–354. (3) Suleman ND, Rasoul HA. War injuries of the chest.

Injury. 1985;16:382–384.

pelling evidence stems from the experience of one

civilian surgeon who treated 1,992 thoracic casualties of the civil war in Lebanon (1969–1982).9

 Of the

casualties this surgeon treated, 282 had a cardiac

injury, 1,251 had a noncardiac thoracic injury as the

major treatment problem, and 456 had one or more

injuries in addition to thoracic trauma. Of the

noncardiac thoracic casualties, a formal thoracotomy

TABLE 19-3

THERAPEUTIC INTERVENTIONS IN THORACIC TRAUMA

24th Evac. Hospital Rambam Medical Center Basrah Teaching

Procedure US Army, Vietnam1 Haifa, Israel2 Hospital, Iraq3

Tube thoracostomy 448 38 113

Thoracotomy 78 6 11

Debridement of thoracic wounds 30

Thoracentesis or no treatment 2 26 31

Major operation outside the thorax ~ 400 35

Data sources: (1) McNamara JJ, Messersmith JK, Dunn RA, Molot MD, Stremple JF. Thoracic injuries in combat casualties in Vietnam.

Ann Thor Surg. 1970;10:389–401. (2) Rosenblatt M, Lemer M, Best LA, Peleg H. Thoracic wounds in Israeli battle casualties during the

1982 evacuation of wounded from Lebanon. J Trauma. 1985;25:350–354. (3) Suleman ND, Rasoul HA. War injuries of the chest. Injury.

1985;16:382–384.

a mini-thoracotomy when they carry out local

wound management. Under general anesthesia,

one or both wounds are extended so that it is possible to inspect the pleural space and lung and, if

necessary, to repair accessible intrathoracic injuries.

Perhaps medical officers will need to reconsider

the consensus that only a minority of thoracic casualties require a formal thoracotomy. The most com-
Anesthesia and Perioperative Care of the Combat Casualty

460

was performed in 818 (54.5% of the total procedures), and of these, an anatomical pulmonary resection was performed in 310. Although the U.S.

Army Medical Department’s experience during the

Persian Gulf War was quite limited, anecdotal observations10 from that war suggest that a greater

fraction of thoracic casualties was treated by

thoracotomy than during the Vietnam War. It is

likely that in future wars, thoracotomy will increasingly be established as the standard of care for

thoracic casualties.

Military trauma anesthesiologists need also to be

aware of a variant of thoracic trauma: the

thoracoabdominal injury (Figure 19-2). In about

10% of the casualties seen during World War II, the

wounding missile was found to have passed from

the chest through the diaphragm into the abdomen.11 The vast experience of surgeons in World

War II indicates that in most such casualties, the

abdominal component was the more life threatening. This is probably because the casualties who

had more-serious thoracic components died before

they could be evacuated from the battlefield. The

anesthetic management of the casualty with a

thoracoabdominal wound will be similar to that of

any abdominal casualty but with this important

exception: unimpaired drainage of air and blood

from the chest must be assured prior to the induction of anesthesia. Once the abdomen is opened, the

hole in the diaphragm establishes a direct connection between the atmosphere and the left pleural

space. Collapse of the left lung is prevented by

positive-pressure ventilation through an endotracheal tube and a functioning chest tube.

Fig. 19-2. A shell fragment entered this casualty’s chest at

the inferior-posterior portion of the left hemithorax at the

site of the hemostat. It passed through the left lung,

diaphragm, spleen, and small bowel before exiting

through the left upper quadrant. The small bowel has

eviscerated through the wound of exit. Notice that the

chest tube is vented to the atmosphere. Suction applied to

the tube would have caused ambient air to be sucked

through the hole in the diaphragm into the thorax. Photograph: Wound Data and Munitions Effectiveness Team

slide collection.

GENERAL PRINCIPLES OF MANAGEMENT

Indications for Thoracotomy

Generally accepted indications for immediate or

early thoracotomy are as follows12:

• an opacified hemothorax on the initial radiograph;

• initial drainage of 1,500 mL of blood, followed by 500 mL or more during the next

hour;

• drainage of 200 to 300 mL of blood per hour

for more than 4 hours;

• massive air leak with continuous bubbling

throughout the respiratory cycle;

• radiographic evidence of massive pulmonary contusion or hematoma, with clinical

and laboratory evidence of a life-threatening shunt or airway compromise secondary

to bleeding into the airway; and

• physical signs of pericardial tamponade or

suspicion of tamponade or shock, and radiographic evidence of a missile in proximity to the heart.

Most casualties with penetrating thoracic injuries will require some type of local wound management, which may or may not require general anesthesia. Casualties with large chest defects, such as

would be associated with a sucking chest wound,

will certainly require operative closure using general endotracheal anesthesia.

Preoperative Evaluation and Preparation

The U.S. Army Medical Department was one of

the first supporters of the American College of
Thoracic Injuries

461

In the American College of Surgeons’ Advanced Trauma Life Support (ATLS) approach, the initial management of the trauma victim is carried out in the following sequence, with the definitive-care phase being

done later:

Secondary Survey

History

Physical examination, including the following

areas:

Head

Maxillae and face

Cervical spine and neck

Chest

Abdomen

Perineum/rectum/vagina

Musculoskeletal system

Neurological systems

Additional laboratory and radiographic studies

as needed

Primary Survey

Airway management with cervical spine control

Breathing and ventilation

Circulation with hemorrhage control

Neurological status

Exposure

Resuscitation, including

Inserting airways, chest tubes, and large-bore

intravenous lines

Infusing crystalloid fluid

Obtaining blood samples

Inserting urinary and gastric catheters

Establishing vital-sign monitors

Obtaining appropriate radiographic studies

EXHIBIT 19-1

INITIAL MANAGEMENT OF TRAUMA VICTIMS

Source: Committee on Trauma, American College of Surgeons. Initial assessment and management. In: Advanced Trauma Life

Support Program for Physicians: Instructor Manual. 5th ed. Chicago, Ill: American College of Surgeons; 1993: 17–37.

Surgeons’ Advanced Trauma Life Support (ATLS)

approach to the initial management of the trauma

victim and has long emphasized such training—

especially for medical personnel assigned to the

field echelons. Military anesthesiologists serving at

third- or fourth-echelon hospitals should, therefore, expect to find that the acute lifesaving interventions—the ATLS ABCs (airway, breathing, and

circulation)—have already been performed before

the casualty arrives at their hospital (Exhibit 19-1).

Nevertheless, there are exceptions. In fact, during

much of the Vietnam War, given the atrophy of the

unit and division echelons of care, casualties commonly arrived at third-echelon hospitals without

having received any care.13 An equivalent situation—the lack of a mature field medical system—

will likely exist in the future whenever the U.S.

military becomes involved in peacekeeping or nation-building missions. As a member of the medical

unit, the anesthesia provider should be involved in

the resuscitation the moment the patient arrives to

the receiving area.

After the initial management has been performed,

the military anesthesiologist will be involved in

the definitive care phase of management. Because the definitive-care phase may involve an

emergency thoracotomy, the anesthesia provider

should perform a specific preanesthesia evaluation

only if time permits. In the conscious patient, a

brief history and physical examination should be

taken (Exhibit 19-2); laboratory investigation should

include recent arterial blood-gas and hematocrit

levels.

Because time is of the essence when dealing with

trauma patients, it is important to have a resuscitation area and an operating room prepared to manage a trauma victim. The anesthesia machine and

monitors should be ready for immediate use. Intravenous tubing and fluid warmers should be available for use, requiring only priming with the intravenous fluid when the patient arrives. Syringes

should be labeled and cardiac drugs immediately

available. A functioning defibrillator should also

be ready.

The essential step that must be taken in preparing the casualty with thoracic injuries for general anesthesia, especially when the operation

also involves another part of the body, is to assure that the potential for the development of an

intraoperative hemothorax or pneumothorax is

minimized by the placement of a functioning

chest tube. Finally, it cannot be stressed too greatly
Anesthesia and Perioperative Care of the Combat Casualty

462

that the military trauma anesthesiologist managing the casualty with a penetrating thoracic injury

will constantly strive to keep the airway free of

secretions.

Monitoring

In addition to the usual noninvasive monitors

(electrocardiograph, pulse oximeter, end-tidal CO2

monitor, automatic blood pressure cuff, precordial

stethoscope), arterial, central venous pressure, and

urinary output monitoring are essential. However,

precious time should not be spent attempting to

place these monitors in unstable, exsanguinating

patients.

Induction of Anesthesia

Unconscious, moribund patients are intubated

immediately without anesthesia, and surgery is

performed without anesthesia until the patient’s

vital signs or state of consciousness indicate a need

for anesthesia. The anesthesiologist is performing

a resuscitation in this scenario, rather than an

anesthetic. Concerns about possible intraoperative

recall may be overstated: providing an ideal, complete anesthetic to a trauma patient at the risk

of hemodynamic instability and possible cardiac

arrest is inappropriate. Scopolamine may be

administered as an amnestic agent, but valuable

time should not be spent to locate or administer this

drug when other, more-important lifesaving tasks

need to be performed. Midazolam may be used but

its hypotensive effect, particularly in the presence

of hypovolemia or when given concurrently with

narcotics, may preclude its use in the trauma patient. Patients in a state of shock are particularly

susceptible to the adverse effects of thiobarbiturates, which should be administered only with

extreme caution. To allow the surgeon to arrest

hemorrhage, ketamine has been advocated as the

drug of choice for induction of anesthesia in

hypovolemic, hemorrhaging patients who require

anesthesia (for further discussion, see Chapter 10,

Intravenous Anesthesia). However, the direct myocardial-depressant effects of ketamine may be unmasked in the patient who is severely physically

stressed and is relying on maximal intrinsic catecholamine secretion to maintain adequate vital

signs. In most cases, though, the anesthesiologist

will have had sufficient time to replace intravascular fluid deficits; therefore, thiobarbiturates or other

induction agents can safely be used. Trauma is

frequently associated with decreased gastric emptying, which places these patients at greater risk

of aspiration pneumonitis; a rapid-sequence induction after preoxygenation is usually indicated.

An awake intubation must certainly be considered

in patients with obvious or suspected airway abnormalities.

Maintenance of Anesthesia

Successful resuscitation of patients with major

chest trauma requires teamwork; blood and fluid

replacement must be prompt and given in appropriate quantities. If patients do not respond to

volume replacement, then ongoing hemorrhage,

tension pneumothorax, or pericardial tamponade

must be suspected. Loss of infused fluid through an

undiagnosed hole in the superior or inferior vena

cava may explain why some patients fail to respond

to fluid therapy. After the surgeon has entered the

chest cavity, compression of the aorta above the

site of bleeding may provide the valuable time

needed to restore blood volume. Although patients

in shock require little, if any, anesthesia, their consciousness rapidly returns when the blood volume

EXHIBIT 19-2

HISTORY AND PHYSICAL EXAMINATION

OF THE CONSCIOUS PATIENT

Brief history:

1. Review of systems

2. Past medical history

3. Past surgical history

4. Previous anesthesia difficulties

5. Family history of anesthetic complications

6. Current medications

7. Allergies

8. Time of last oral intake

Brief physical examination:

1. Global assessment

2. Evaluation of the airway

3. Respiratory and cardiovascular examinations

4. Vital signs
Thoracic Injuries

463

is restored. At this point, anesthesia can be maintained with oxygen, narcotics, neuromuscular

blocking drugs, amnestics, and small quantities of

inhalational agents, if required. It is prudent to

avoid nitrous oxide in patients with chest trauma

because the gas tends to collect in the dependent

areas of the lung. The risk is that nitrous oxide will

expand in the closed chest and create a pneumothorax. (Nitrous oxide is not available in deployable

hospitals.)

Special considerations with the use of neuromuscular blocking agents in the trauma patient deserve

mention. Succinylcholine, the rapid-acting depolarizing relaxant often used for rapid-sequence inductions, is known to cause profound hyperkalemia in patients who have extensive muscle damage,

particularly if the drug is given 24 to 36 hours after

the traumatic insult. Alternatives include the

nondepolarizing relaxants, such as vecuronium

given at 0.28 mg/kg, for conditions requiring rapid

intubation. This agent is useful during the maintenance of anesthesia because it has minimal hemodynamic effects. The vagolytic actions of pancuronium may be undesirable because the tachycardia may lead to further confusion in distinguishing drug effect from hypovolemia or inadequate

levels of anesthesia. d-Tubocurarine and atracurium

should probably be avoided because of their histamine-mediated hypotensive effects. It is important

to remember that all neuromuscular blocking agents

are subject to aberrant behavior in the presence of

changing acid–base status, altered metabolism and

excretion, hypothermia, and certain antibiotics. For

this reason, it is mandatory to monitor the status of

the neuromuscular blockade.

Hypothermia is a major problem in traumatized

patients undergoing exploratory surgery, and every effort should be made to maintain a normal core

body temperature. Heated humidifiers, low gas

flows, warmed intravenous and irrigating fluids,

and a warmed operating room can help maintain

normothermia. Certainly, heating lamps, warming

blankets, and plastic to wrap exposed body surfaces

can also be used.

Positioning for Operation

The position of patients with thoracic injuries

(whose major injury does not involve the thorax)

will obviously depend on the location of that injury;

the usual position will be with the trunk supine.

The position of casualties who are to have an actual

thoracic procedure will depend on the indication

for the operation. Most thoracic surgeons use an

anterolateral incision for the casualty who is agonal

(ie, a casualty who exhibited one or more signs of

life [motion, spontaneous respiration, palpable

pulse] shortly before arrival at the hospital, but who

is now lifeless) or in profound shock, although a

few prefer a median sternotomy for the operative

approach. Thus, the desired position for an emergency operation is supine. Because the needed

operation is best done through a posterolateral

thoracotomy incision with the patient in the right

lateral decubitus position, there are two exceptions

to this rule:

1. the unusual casualty who is known to have

an injury to the proximal left subclavian

artery, and

2. the casualty who has sustained blunt

trauma to the chest and has radiographic

evidence of a left hemothorax and a widened superior mediastinum, and who,

therefore, may have a proximal descending aortic disruption.

Patients who are undergoing thoracic surgery in

which the indications are less emergent (eg, control

of nonexsanguinating hemorrhage, a large air leak,

repair of a chest-wall defect, or simply to debride

the wounds of entrance or exit) are placed in the

decubitus position so that a posterolateral incision

can be made. Care must be taken to ensure that

there is no pressure on the brachial plexus of the

dependent arm, and that the thorax and abdominal

wall are free to move without restricting respirations. Endotracheal tube position and the position

of all monitors must be checked for dislodgement

following patient positioning. Patients with concurrent orthopedic injuries may be difficult to position because of pain and the potential for dislocation or worsening of the injury.

Postoperative Care

Most patients presenting for surgery secondary

to battlefield chest trauma require postoperative

care in an intensive care unit until an adequate level

of physiological homeostasis can be achieved. The

military trauma anesthesiologist is expected to play

a significant role in the postoperative care of these

patients, especially in the realm of acute pain and

ventilatory management.14
Anesthesia and Perioperative Care of the Combat Casualty

464

DIAGNOSIS AND MANAGEMENT OF SPECIFIC INJURIES

fractures of three or more ribs in two places on the

same side. This produces a segment of the chest

wall that responds to changes in pleural pressure,

as opposed to the muscular action of the chest wall,

resulting in a paradoxical respiratory pattern. This

injury is most commonly associated with blunt

trauma to the chest wall and involves the anterolateral aspect of the chest. The posterior wall is

rarely involved because it is heavily fortified with

muscle. The flail chest injury is rarely isolated and

is usually an ominous sign, indicating serious underlying injuries to intrathoracic or intraabdominal

organs or both. This condition is often difficult to

diagnose and may go unnoticed for extended periods, often overshadowed by more-overt injuries.

Chest radiography may not reveal fractures unless

the films are overpenetrated and oblique views are

taken. Flail chest may not be apparent on simple

inspection, as chest-wall muscular spasm may be

able to splint the segment until the muscles become

fatigued. Palpation is more likely to be diagnostic

than inspection, with the presence of crepitus and

abnormal respiratory motion aiding in the diagnosis. Serial blood-gas measurements can help establish the diagnosis, because the clinical hallmark of

flail chest is hypoxemia.

Flail chest can cause hypoxemia by two mechanisms: (1) intrapulmonary shunting due to perfusion of the poorly ventilated, contused lung; and (2)

atelectasis caused by compromised ventilatory mechanics. The pendelluft phenomenon, which is a toand-fro movement of air from the damaged to the

normal lung, was once thought to make a significant contribution to hypoxemia. However, it has

been shown that there is an increase in ventilation

and improved gas exchange on the injured side.17

The hypoxia observed in flail chest is now recognized to be caused by abnormalities in the contused

lung underlying the flail segment.18 Thus, the modern treatment of flail chest focuses on preventing

the arterial desaturation (that results from the shunting) from reaching life-threatening proportions.

Stabilization of the flail segment, maintenance of

adequate ventilation, oxygen enrichment, physical

therapy, and effective pain relief should all be tried;

however, a period of intubation and ventilation

may be necessary. The criteria for intubation, which

should only serve as a guide, include:

• partial pressure of arterial oxygen (PaO2)

< 70 mm Hg with oxygen enrichment,

Rib Fractures

The ribs are the most commonly injured component of the thoracic cage, and the incidence of serious complications increases with the number of ribs

fractured. This increase is a reflection of the greater

traumatic forces associated with multiple rib fractures. As a general rule, a young, otherwise healthy,

active-duty recruit with a flexible chest wall is less

likely to sustain a rib fracture than is a geriatric

patient with thoracic trauma. With this in mind, the

presence of multiple rib fractures in young patients

implies a sizable transfer of force. Multiple rib

fractures most commonly involve the seventh

through tenth ribs and thus are often associated

with hepatic or splenic lacerations. Acute gastric

dilation commonly accompanies left-sided fractures and may increase the likelihood of acid aspiration. Fractures of the upper ribs (first through

third) should be regarded as harbingers of serious

blunt trauma to the chest. The bony framework of

the upper limb and its muscular attachments provide a barrier to injury in this area. Therefore,

severe maxillofacial, cervical, neurological, pulmonary, and vascular injuries may accompany upperrib fractures.15

Rib fractures, even in the absence of underlying

cardiopulmonary trauma, may contribute to serious pulmonary complications. The associated pain

and reflex muscle splinting can exacerbate alveolar

hypoventilation, resulting in retention of secretions,

atelectasis, and respiratory failure. Taping or binding the ribs will cause even more splinting and

further compromise. A tidal volume of less than 5

mL/kg or a forced vital capacity of less than 10 mL/

kg indicates severe splinting.16 Adequate analgesia

is essential in the management of rib fractures. The

use of intercostal nerve blocks is attractive because

it avoids the respiratory depression associated with

systemic narcotic administration. Comparable analgesia of longer duration and with less potential

for systemic toxicity may be achieved with continuous thoracic epidural analgesia. Intrapleural injection of local anesthetics is another form of analgesia

for rib fractures. The efficacy of this technique,

however, is controversial at this time.

Flail Chest

Flail chest may be defined as an abnormal movement of the chest wall occurring as a result of
Thoracic Injuries

465

• partial pressure of arterial carbon dioxide

(PaCO2) > 50 mm Hg,

• pH < 7.25,

• tachypnea > 30/min,

• vital capacity < 15 mL/kg, and

• negative inspiratory force < –20 cm water.

Both external stabilization of the flail segment by

traction and internal fixation with intramedullary

pinning of the fractured ribs have been described.19,20

Continuous electrocardiographic monitoring is

essential because flail chest can often be associated with cardiac contusions, from which arrhythmias may arise. Frequent arterial blood-gas analyses, along with other laboratory studies, justify placing an arterial line. Pulmonary artery catheterization,

which may be available in deployable hospitals,

may help with the evaluation of cardiac performance and guide fluid management. This is especially necessary because the injured lung underlying the flail segment is sensitive to both

underresuscitation of shock and fluid overload, the

latter condition leading to pulmonary edema in the

injured lung tissue and a further impairment of gas

exchange.21 In intubated, ventilated patients, excessive airway pressure can also cause an iatrogenic

injury by mechanically disrupting damaged alveolar capillary membranes in the lung underlying the

flail segment. This may enlarge the volume of the

contusion, but a more serious problem is the increased likelihood of systemic air embolism.22

Sucking Chest Wound

An open, sucking, or blowing chest wound is a

serious injury that is usually found at the site where

a yawing or tumbling bullet has exited or where a

large fragment from an explosive munition has

entered. The most serious component of the wound

is usually the injury to the underlying lung. The

characteristic appearance is of bloody foam being

alternately sucked into and blown from the wound

(Figure 19-3). In this condition, intrapleural pressure equalizes with the atmosphere, resulting in a

diminished movement of air on the affected side.

The immediate treatment of this condition is to

occlude the defect but provide for egress of air from

the chest cavity by inserting a chest tube with a oneway valve. Sucking chest wounds are not especially

common among combat casualties. In the Israeli

series, they accounted for only seven (11%) of the

total of the thoracic casualties.2 The reason for their

low prevalence is that the intrathoracic component

of the injury is much more likely to be life-threatening than is the hole itself. Once the intrathoracic

component has been treated, surgical treatment is

directed toward achieving an air-tight closure of

the chest wall defect.

Acute Traumatic Hemothorax

Hemothorax can occur with both penetrating

and nonpenetrating thoracic trauma and is usually

caused by blood emanating from injuries of the

heart, great vessels, pulmonary parenchyma, or

chest wall.23 The diagnosis of hemothorax is made

on the basis of history and clinical examination of

the chest. When a significant quantity of blood has

accumulated in the chest cavity, the trachea may be

deviated, the chest wall is dull to percussion, and

breath sounds are diminished on auscultation. A

chest radiograph and an electrocardiogram should

be obtained for all patients except those presenting

in extremis. Approximately 500 mL of blood must

accumulate in the chest cavity before it is radiologically detectable.

Because hypovolemia from blood loss is the most

common problem in patients who present with significant chest injury, the immediate treatment should

be directed toward restoring blood volume. Two

large-bore intravenous cannulae should be inserted

as soon as possible. Central venous pressure moniFig. 19-3. This casualty had a sucking chest wound. A

large fragment entered his back; frothy material can be

seen in the base of the wound. Photograph: Wound Data

and Munitions Effectiveness Team slide collection.
Anesthesia and Perioperative Care of the Combat Casualty

466

toring may be useful in both diagnosing and managing patients who have mechanical interference

with ventilation, as the central venous pressure is

low in the presence of severe hypovolemia but

elevated in the presence of a chest cavity full of

blood. Oxygen therapy is mandatory. Tube

thoracostomy should be performed as soon as possible because it is not only therapeutic, it also provides an assessment of cumulative and ongoing

blood loss, facilitates reexpansion of the lung, and

simplifies autotransfusion when major bleeding is

encountered. In most cases, the source of the bleeding is the pulmonary vessels, which normally have

low perfusion pressures. On the other hand, bleeding from systemic vessels or the heart is usually

more persistent and voluminous.

For casualties who have an indication for operative intervention but who are stable (ie, blood pressure > 100 mm Hg, pulse rate < 100, good peripheral

perfusion and ventilation), the thoracotomy is performed in the operating room. Immediate

thoracotomy in the admitting area of the hospital

may be indicated in patients who become agonal on

arrival. The best results have been obtained in

casualties who have penetrating thoracic injuries,

and the poorest results in those sustaining blunt

trauma—especially when the abdomen is involved.

Regardless of the etiology, survival in this group of

casualties is poor. In one recent series,24 survival

was 6% in those with blunt trauma and 27% for

casualties with penetrating wounds of the chest.

The reasons for performing a thoracotomy are to

• decompress a tension pneumothorax or

pericardial tamponade, if present;

• perform open-chest cardiac massage; and

• stop bleeding if it arises within the thorax

or, by occluding the descending aorta, to

slow bleeding if it arises from the abdomen.

After the airway has been intubated, if necessary

via cricothyroidotomy, an anterolateral incision is

made on the side of injury, the pericardial sac

opened, and cardiac compressions begun. Bleeding

sites are controlled by direct pressure or by application of a clamp or Rommel tourniquet around the

hilum of the lung. The military trauma anesthesiologist should anticipate the need to correct severe

metabolic acidosis and to manage a variety of malignant cardiac arrhythmias. The patient is then

transported to the operating room for definitive

treatment.

The management of agonal casualties is very

labor and resource intensive. The likely poor outcome, even with the best of care, has led some

authorities25 to argue that emergency thoracotomy

for agonal victims of truncal trauma has no place in

combat casualty care. The military trauma anesthesiologist, in consultation with the hospital thoracic

or trauma surgeon and the hospital commander,

should develop an agreed-upon triage policy for

such casualties. By necessity, any such policy will

have to take account of the existing tactical situation.

Cardiac Tamponade

Although cardiac tamponade is found in casualties who require emergency thoracotomy, its occurrence is not limited to this group. In some casualties, the presentation of cardiac tamponade may be

quite subtle (Figure 19-4). Acute, traumatic pericardial tamponade is caused by the collection of blood

or other fluid (eg, serous exudate) within an intact

pericardial sac. This sac is composed of a fibrous,

poorly compliant membrane. Rapid accumulation

of 100 to 200 mL of fluid in this closed space restricts

filling of the cardiac chambers during diastole, which

produces a fixed, low, cardiac output. Positivepressure ventilation will lower cardiac output even

further, as will any cardiac depressant.

The diagnosis of cardiac tamponade requires a

high degree of clinical suspicion. It should always

be suspected in patients with wounds in the vicinity

of the neck, precordium, or upper abdomen, and

Fig. 19-4. (a) This casualty was wounded when a grenade fragment penetrated his back. He was initially neither hypotensive

nor in much distress but while being observed developed tachycardia, dyspnea, and distended neck veins. (b) The chest

radiograph shows a fragment within the silhouette of a globular-shaped heart. A thoracotomy was performed because of

the casualty’s deteriorating clinical state and the appearance of the radiograph. (c) The pericardium has been opened and

several blood clots have been extruded. (d) The removed clots. (e) A small defect, which was not then bleeding, in the free

wall of the left ventricle. (f) The fragment after its removal from the myocardium. The tip of the hemostat serves as a reference

for size. The left ventricular wall had not been perforated, possibly because of the fragment’s small size. Other fragments

lacerated the stomach and spleen; these were found during a subsequent laparotomy. Photographs: Swan Vietnam Surgical

Slide Collection.
Thoracic Injuries

467

a d

c

f

b

e
Anesthesia and Perioperative Care of the Combat Casualty

468

especially in patients who are in shock. The classic

signs, although present in only 41% of patients with

penetrating cardiac wounds,26 include Beck’s triad:

hypotension, distended neck veins, and distant

heart sounds. Other signs include pulsus paradoxus,

which is a decline in systolic blood pressure of 10

mm Hg or more on inspiration. This is of limited

value in the field, however, as continuous arterial

pressure monitoring may not be possible.27 Paradoxical filling of neck veins on inspiration

(Kussmaul’s sign) may be too subtle to detect in

uncooperative, struggling patients. If significant

blood loss has occurred, distension of neck veins

may not occur. Equalization of pressures across the

heart, measured by a pulmonary artery catheter, is

very suggestive of tamponade. The chest radiograph may reveal a large, globular heart shadow,

and the electrocardiogram will be either normal or

show nonspecific ischemic changes. Occasionally,

the electrocardiogram will show electrical alternans,

which is usually diagnostic of tamponade.

Again, it should be emphasized that heavy reliance is placed on clinical impression in diagnosing

patients on the battlefield with cardiac tamponade.

Shock and a wound in the anterior chest indicate cardiac

tamponade until proven otherwise. Elevation of the

central venous pressure is strong confirmatory evidence of the diagnosis, and treatment should be

started immediately. The definitive treatment of

this condition is surgery as soon as possible.

Pericardiocentesis may be used to relieve the

tamponade in rapidly deteriorating patients. However, this is of limited value because blood rapidly

reaccumulates in the pericardial sac.

The patient should be prepared and draped for

surgery, and an arterial line should be inserted

prior to the induction of anesthesia. The administration of a general anesthetic to a patient with a significant

tamponade is potentially lethal.

28,29 Almost any maneuver, other than administration of 100% oxygen,

including positive-pressure ventilation, causes deterioration.30 Inhalational agents or thiopental cause

further cardiac depression and impairment of diastolic filling. Peripheral vasodilation associated with

these agents further impairs filling. Anesthetic goals

include maintaining adequate preload with copious volume infusion (central venous pressure at

least 15 cm H2O), and avoiding vagotonic medications (eg, narcotics). It is important to maintain

sinus tachycardia in the face of limited stroke volume to maximize cardiac output. The combination

of ketamine and pancuronium is ideal for this purpose. The recommended dose of ketamine for patients with diminished cardiac output is 0.25 to 0.50

mg/kg. Despite careful anesthetic management,

the patient’s condition may deteriorate before the

tamponade is relieved. If deterioration occurs,

isoproterenol has been advocated,31 infused at a

rate of 0.1 μg/kg/min, and titrated to effect. When

the pericardium is decompressed, the patient’s vital signs usually improve instantaneously.

Cardiac Contusions

Myocardial contusion is the most common cardiac injury due to nonpenetrating trauma. Depending on the sophistication of the diagnostic

armamentarium and the definition of the condition,

cardiac contusions have been reported in approximately 15% to 70% of trauma patients who sustain

blunt chest trauma. Rapid deceleration occurring

during motor vehicle accidents is the most common

cause of cardiac contusions. The heart is subjected

to marked anteroposterior compression resulting

in rupture of the intramyocardial vessels, which

bleed into the myocardium. Subsequently, myocytes

may die and undergo fragmentation. Iatrogenic

trauma caused by closed-chest massage during cardiopulmonary resuscitation may also be responsible for myocardial contusion. The right ventricle

is injured more frequently than the left during cardiopulmonary resuscitation, due to its proximity to

the chest wall. However, the valves in the left side

of the heart, especially the aortic valve, are more

susceptible to injury than those in the right side of

the heart.16

Symptoms of myocardial contusion may be similar to those of myocardial infarction or pericarditis,

because anginal chest pain is the most common

presenting complaint. However, contusion pain is

not relieved by nitroglycerin. Many trauma patients with myocardial contusion report few or no

symptoms from their cardiac injuries. Ventricular

arrhythmias are the most common clinical sign of

cardiac contusion. Conduction disturbances are

more commonly associated with injuries to the right

atrium and ventricle.32 Other signs may be a current

of injury on the electrocardiogram or a pericardial

friction rub; there may be no change at all in cardiac

examination. The diagnosis of cardiac contusion can

be a real dilemma for the clinician, as most routine

and sophisticated tests have proven unreliable.

Casualties presenting with myocardial contusion should be treated in the same manner as those

presenting with myocardial infarctions. Many casualties with this condition need immediate sur-
Thoracic Injuries

469

gery to treat their other injuries. Because the right

ventricle is particularly vulnerable to contusion

owing to its proximity to the anterior chest wall,

right ventricular dysfunction and failure may complicate perioperative management. The right ventricle is sensitive to afterload; therefore, conditions

that may increase pulmonary vascular resistance

(ie, hypoxia, hypercarbia) should be avoided. Adequate preload is usually necessary in the setting of

right ventricular dysfunction; intravascular volume

resuscitation is therefore mandatory.

Cardiac Rupture

Rupture of the heart is a common cause of immediate death in victims of blunt trauma. In

nonpenetrating injuries, severe compression may

so raise cardiac chamber pressure and wall stress

that the myocardium ruptures. Thus, the mechanism is similar to the process that gives rise to

myocardial contusion. Puncture of the heart by ribs

broken by blunt trauma has also been described. In

combat casualties, penetrating injuries are a more

frequent cause of cardiac perforations than is blunt

trauma. Although right ventricular perforations

may appear to predominate, a comparable incidence of left ventricular injuries has been described.33

Because of the higher immediate mortality associated with ventricular trauma, patients with atrial

perforations are more frequently encountered in

the operating room.

The clinical presentation of cardiac rupture or

perforation is determined by the status of the

pericardium. With an open pericardial wound,

blood extravasating from the heart drains freely

into the pleural space, producing a rapidly fatal

hemothorax. If the pericardial defect is small, or if

it is occluded (as may happen on rare occasions by

clotted blood or by the adjacent lung), the patient

may not exsanguinate but live long enough to develop the signs of cardiac tamponade. The anesthetic management of cardiac rupture is similar to

that for pericardial tamponade, except that

exsanguination makes emergency thoracotomy

more common.

Cardiopulmonary bypass, although usually not

available in combat zone hospitals, may be required

to repair some cardiac defects. Although traumatic

ventricular septal defects may close spontaneously,

most of them require surgical closure through the

left ventricle, utilizing cardiopulmonary bypass.

Vasodilators often produce some degree of clinical and hemodynamic improvement. However,

it should be emphasized that vasodilators

are contraindicated in severely hypovolemic patients.

Injuries to the Coronary Arteries

The incidence of coronary artery laceration following penetrating cardiac injuries has been reported34 to be about 4%. Division of a coronary

artery invariably leads to hemorrhage and tamponade,

and may cause myocardial infarction. Because the

right coronary artery is protected by the sternum,

most injuries involve the left coronary artery or its

branches. Coronary artery occlusion after blunt

chest trauma has been reported.35 In these cases,

myocardial infarctions evolved after the traumatic

injury in patients without preexisting coronary atherosclerosis.

Several mechanisms may be involved in the

pathogenesis of myocardial infarction after blunt

chest trauma. In perhaps the simplest scenario, the

forces accompanying an episode of blunt trauma

could dislodge a previously adherent intramural

plaque, resulting in intraluminal obstruction of the

involved coronary artery.36 Patients with preexisting atherosclerotic heart disease also may be at

increased risk for infarction because of traumainduced hemorrhage into a plaque, which is known

to be richly vascularized with fragile, thin-walled

capillaries.37 A third possible mechanism of ischemic

injury is trauma-induced coronary vasospasm. Although spasm also occurs in normal vessels,

angiographically visualized spasm often occurs at a

site of atherosclerotic narrowing.38 Other etiologies

of traumatic infarction include coronary thrombosis

due to vascular trauma, direct transection of the

coronary arteries, coronary embolization, and dissecting aneurysm.39

In the absence of cardiac tamponade, the anesthetic management of these casualties should be

similar to that for patients with coronary artery

disease with unstable angina. A variety of techniques are consistent with the hemodynamic goals

of avoiding tachycardia and extremes of blood pressure. In young soldiers with good ventricular function, a combined technique with high-dose narcotics and an inhalational anesthetic agent is ideal:

intraoperative sympathetic reflexes are reliably

blunted, while myocardial contractility and oxygen

consumption are appropriately depressed. Although there may be no ideal induction technique

for the patient with ischemic heart disease and a full

stomach, a moderate dose of narcotic (eg, 10–15 μg/kg
Anesthesia and Perioperative Care of the Combat Casualty

470

fentanyl) combined with etomidate (0.1–0.2 mg/kg)

and succinylcholine results in a stable induction,

with adequate blunting of autonomic responses

to laryngoscopy. In the setting of severe skeletal

muscle injury, particularly if more than 24 to 36

hours have elapsed since the injury, nondepolarizing

relaxants may be preferable because of the possibility of succinylcholine-induced hyperkalemia.

The common presentation of the casualty with a

coronary artery injury caused by penetrating trauma

is pericardial tamponade. Because direct repair of

the arterial laceration in a beating heart is usually

not feasible, and because the cardiopulmonary bypass apparatus that would allow the construction of

an aortocoronary saphenous graph bypass is not

likely to be available in field hospitals, the military

surgeon has little option but to ligate the injured

artery. Given this circumstance, the military trauma

anesthesiologist should be prepared to treat potentially life-threatening cardiac arrhythmias and cardiogenic shock.

Injuries to the Great Vessels

The thoracic aorta can be injured as a result of

penetrating or blunt trauma to the chest. The resulting hemorrhage is usually devastating, allowing

only approximately 15% of patients to reach a field

hospital alive.40

In the U.S. military, the great majority of aortic

ruptures result from motor vehicle accidents and

airplane crashes. Abrupt deceleration of the thorax

(a) causes compression and displacement of the

heart and (b) creates shearing and bending stresses

in the aortic wall, which are greatest at the origin of

the subclavian artery and, in the ascending aorta, at

the level of the coronary arteries.41 A minority of

these patients (perhaps 10%) survive because of

containment and tamponade of the hemorrhage by

adjacent mediastinal structures. In the proximal

descending aorta, the aortic adventitia may remain

intact and temporarily prevent exsanguination.

Sudden aortic rupture may develop in these patients at a later time.

Penetrating chest trauma may also involve the

great vessels. Depending on whether the vessels

are injured at an intrapericardial or an extrapericardial location, the clinical presentation is usually

one of acute tamponade or massive hemothorax.

These casualties may have sustained one or more

penetrating cardiac injuries as well, but severe

hypovolemia may account for the frequently atypical hemodynamic findings.

The clinical findings of aortic rupture include the

diagnostic triad that is seen in more than 50% of

cases42:

• increased arterial pressure and pulse amplitude in the upper extremities,

• decreased pressure and pulse amplitude in

the lower extremities, and

• a widened superior mediastinum seen on

the chest radiograph.

Other clinical and radiographic findings are included in Exhibit 19-3. An active search for these

clinical and radiographic findings is important during evaluation because as many as one third of

patients with aortic rupture have minimal or no

external signs of chest trauma.43,44

When dealing with injuries to the major thoracic

vessels, the foremost goal of the anesthesiologist is

to simply maintain an adequate blood volume, which

allows the surgeon the time needed to find the

source of bleeding and, if possible, to repair the

injured vessel. Ischemia of the abdominal viscera

and spinal cord may occur during the period of

proximal aortic clamping; the reported incidence of

EXHIBIT 19-3

CLINICAL AND RADIOGRAPHIC

FINDINGS OF AORTIC RUPTURE

Clinical:

Increased arterial pressure and pulse amplitude of upper extremities

Decreased arterial pressure and pulse amplitude of lower extremities

Retrosternal or interscapular pain

Hoarseness

Systolic flow murmur over the precordium or

medial to the left scapula

Neurological deficits in the lower extremities

Radiographic:

Widened mediastinum

Unsharp aortic contours

Widened paraspinal interfaces

Opacified pulmonary window

Broadened paratracheal stripe

Displacement of the left main-stem bronchus

Rightward deviation of the esophagus

Sternal or upper-rib fractures or both

Left hemothorax
Thoracic Injuries

471

paraplegia in survivors ranges from 1.0% to 11.7%.41

Prophylactic measures for preserving spinal cord

viability include partial cardiopulmonary bypass,

heparin-coated shunts, partial bypass of the left

side of the heart, draining the cerebrospinal fluid,

and inducing systemic hypothermia.

The presumed mechanism of paraplegia in these

patients is ischemia of the spinal cord caused by

damage to the intercostal vessels that supply the

spinal cord. Monitoring of somatosensory evoked

potentials may be useful in heralding spinal cord

ischemia but is not practicable in field hospitals.45

The kidney is the abdominal organ at greatest

risk for ischemic injury during the period of aortic

occlusion. Preserving distal perfusion with shunts

or partial bypass is associated with a lower incidence of postoperative renal dysfunction; however,

because the needed equipment is not available in

the field, the military trauma anesthesiologist has

no other recourse than to use mannitol, renal-dose

dopamine, and/or diuretics as part of a strategy for

renal protection similar to that used for abdominal

aortic aneurysm surgery.46

Intraoperative monitoring should include placing a right radial arterial line and a lower-extremity

arterial line for monitoring distal aortic pressure.

The surgeon’s possible clamping of the left subclavian artery would make monitoring the left radial

arterial pressure impossible during that time. In all

but the most emergent cases, pulmonary arterial

catheterization is desirable because proximal aortic

occlusion imposes a severe afterload stress on the

left ventricle.

A double-lumen endotracheal tube is desirable

because it allows the left lung to be collapsed to

facilitate surgical exposure. Equally important,

however, is the fact that the dependent right lung

can be isolated from the parenchymal hemorrhage

that may occur in the left lung as a result of pulmonary contusion.

Pneumothorax

Pneumothorax occurs secondary to blunt or penetrating trauma to the chest wall. Less obvious

pneumothoraces occur as a result of penetration of the

chest wall and lung by sharp objects, such as bullets,

knives, or rib fragments. Pneumothoraces of less than

20% are usually not clinically detectable. Patients may

complain of chest pain, which is accentuated by deep

breathing. Cyanosis may be evident, and with larger

pneumothoraces, the trachea can be deviated. Percussion of the chest reveals a tympanitic sound, and

breath sounds may be diminished or absent. Conditions that can mimic pneumothorax include hemothorax or atelectasis. Radiological examination is the

best diagnostic aid available, and all films should be

exposed during expiration, if possible.47 The presence

of rib fractures or surgical emphysema should provide a clue to the diagnosis. In trauma patients,

pneumothoraces with a volume greater than 10%

should be treated by tube thoracostomy. Temporizing the treatment is inappropriate for the patient who

may require intubation and positive-pressure ventilation during surgery for extrathoracic injuries, as the

pneumothorax may enlarge under these conditions.

Therefore, the prophylactic insertion of a chest tube

is indicated.

A tension pneumothorax occurs when air enters

the pleural cavity during inspiration but, owing to

a ball-valve action, cannot escape during expiration.

In conscious patients, rapid deterioration is noted.

The cardinal signs of a tension pneumothorax are

• cyanosis,

• marked decrease in pulmonary compliance,

• rapid deterioration of vital signs,

• diminished or absent breath sounds, and

• tracheal deviation.

This condition can be easily confused with pericardial tamponade or shock, secondary to hypovolemia; however, the hypertympanic percussion

note over the ipsilateral chest usually makes differentiation possible.

The casualty shown in Figure 19-5 is a particularly dramatic presentation of a tension pneumothorax. However, it is important to stress that a

tension pneumothorax is a clinical rather than a

radiological diagnosis. Two factors contribute to

the hemodynamic deterioration: (1) hypoxia from

decreased gas exchange and (2) increased impedance of venous return into the chest due to the

mechanical distortion of the mediastinum that is

caused by the expanding pneumothorax. During

general anesthesia, a dramatic decrease in pulmonary compliance should alert the anesthesiologist

to the problem. Nitrous oxide should be discontinued if it is being administered, as it accentuates the

size of the pneumothorax.48 As soon as a hemodynamically significant tension pneumothorax is suspected, the anesthesiologist might need to perform

temporizing measures, including the immediate

insertion of a large-bore needle into the second

intercostal space along the midclavicular line. A

“hissing” sound may be created by the escaping,
Anesthesia and Perioperative Care of the Combat Casualty

472

1. Sudden, forceful compression is the most

common insult causing tracheobronchial

injuries during blunt thoracic trauma. This

anteroposterior compression combined

with simultaneous lateral expansion of the

lungs can result in severe traction on the

pericarinal portion of the trachea.

2. Acute increase in intrabronchial pressure

may be caused by reflex glottic closure at

the moment of impact.

3. Shearing forces at points of fixation of the

intrathoracic airways, caused by rapid deceleration, may account for the preponderance of disruptions near the carina.

Dyspnea, cough, painful hemoptysis, and subcutaneous emphysema are the most common clinical

findings in patients with tracheobronchial disruption. However, 10% of patients are nearly asymptomatic,51 which accounts for the frequent delays in

diagnosis. Auscultation of the heart may reveal a

crunching sound associated with pericardial air,

also known as Hamman’s sign. When the site of

disruption freely communicates with the mediastinal pleura, pneumothorax results, and tube

thoracostomy and suction often fail to reexpand the

affected lung. When the pleural space and the site

of disruption do not communicate, there is little or

no pneumothorax, and mediastinal air may be the

only radiographic abnormality. In addition to

pneumothorax and pneumomediastinum, indicative radiographic findings include subcutaneous

and deep cervical emphysema. With complete

transection of a main bronchus, the superior margin

of the affected lung drops below the level of the

transection. This occurs because the lung is deprived

of its normal bronchial tethering in the thoracic cage.

All patients with suspected tracheal or bronchial

injury require diagnostic bronchoscopy as soon as

they are stable. Blind endotracheal intubation without endoscopic visualization of the tracheobronchial tree is unlikely to be successful and may produce further trauma because the distal trachea is

displaced posteriorly. In addition, acute airway

obstruction may develop when the endotracheal

tube enters a false passage and occludes the tracheal lumen. Both a surgically guided oral

intubation of the distal tracheal segment and removal of the initial surgical airway are acceptable

means of allowing surgical repair of the tracheal

separation.

When the disruption and distal segment can be

visualized clearly, a double-lumen tube can be inserted distal to the tracheal tear or, in the case of

Fig. 19-5. This casualty was killed by a perforating gunshot wound of the right hemithorax. A radiograph was

taken before the autopsy was performed. A tension

pneumothorax with massive shift of the mediastinum is

apparent. Photograph: Wound Data and Munitions Effectiveness Team slide collection.

pressurized air. Intravenous extension tubing can

then be attached to the catheter and placed under

water seal (ie, submerging it in a liter bottle of

sterile water). Care must be taken to keep the water

bottle lower than the patient; otherwise, the flow

may be reversed, causing a hydrothorax. Temporizing measures should be replaced as soon as possible by the more definitive closed-system tube

thoracostomy.

Tracheal and Bronchial Injuries

Tracheal and bronchial injuries are uncommon

sequelae of thoracic trauma but are among the most

serious encountered in thoracic surgery. Although

most penetrating wounds to these structures are

caused by fragments, these injuries also occur following blunt trauma associated with high-speed

travel. A 2.8% incidence of tracheobronchial rupture has been reported49 in patients who succumbed

to blunt chest trauma. Approximately 80% of tracheobronchial disruptions occur within 2.5 cm of the carina. Three mechanisms may explain this finding50:
Thoracic Injuries

473

bronchial disruption, into the contralateral bronchus. Alternatively, the area of disruption can be

visualized directly with a fiberoptic bronchoscope;

then the instrument can be used as a guide over

which an endotracheal tube can blindly be passed

into the distal tracheal segment. This approach is

equally acceptable for bronchial disruption, although it is preferable to intubate the uninjured

bronchus selectively for ventilation during bronchial repairs. Therefore, the military trauma anesthesiologist must have available a variety of sterile

endotracheal tubes that can be passed into the operative field and used to intubate the distal airway

prior to and during its anastomosis to the proximal

segment. Alternative techniques such as simply

insufflating oxygen into the distal airway or employing high-frequency jet ventilation using

uncuffed catheters in the contralateral bronchus

have also been described.52

Parenchymal Lung Lacerations

Extensive laceration of the lung parenchyma—

such as might occur when an assault-rifle bullet

yaws and tumbles during its passage through the

lung—can create one of the most difficult therapeutic problems for the military trauma anesthesiologist. Not only will there be massive leakage of air

into the pleural space, which will make difficult the

maintenance of an acceptable tidal volume, but the

normal anatomical proximity of airways and blood

vessels in the lungs potentiates (1) the passing of

blood into airways and (2) the passing of air into the

circulation. The first condition causes an airway

obstruction as the casualty literally drowns in blood.

The second causes rapidly fatal systemic air

embolization. The simultaneous leakage of air into

the pleural space and passage of blood into the

tracheobronchial tree can best be managed by having the anesthesiologist pass a standard endotracheal tube into the bronchus of the uninjured lung.

(The use of a double lung tube in this situation is too

time consuming to be safe.) Once the injured lung

has been isolated by the anesthesiologist, the surgeon, after exposing the injured lung, can then

cross-clamp the pulmonary hilum. The appropriate

surgical management may be to perform an anatomical pulmonary resection—a lobectomy or

pneumonectomy—rather than to attempt a repair

of the laceration (Figure 19-6).53

Systemic air embolism is a catastrophic complication that suddenly converts a previously stable

patient into one who is agonal. Increasingly, evidence shows that cerebral and coronary air emboli

are common causes of death in victims of penetrating lung injuries.22 There is frequently a causal

relation to the application of positive pressure to

the airway. The treatment, insofar as there is one,

consists of

• immediate performance of a thoracotomy,

• application of a large clamp or Rommel

tourniquet around the hilum of the injured

lung to prevent further embolization, and

• exposure of the heart to confirm the diagnosis (air bubbles should be visible in the

coronary vessels).

If the diagnosis is confirmed, the surgeon manually occludes the ascending aorta and manually

compresses the heart so as to drive the air bubbles

through the coronary arteries and into the coronary

sinus. The management of the cerebral component

is a matter for conjecture.

Traumatic Rupture of the Diaphragm

Traumatic rupture of the diaphragm is a relatively uncommon injury, seen in 2% to 3% of patients with blunt chest trauma.18 In the context of

military operations, it is most frequently seen in

casualties who are injured when the vehicle in which

they are riding detonates a buried antitank mine.

The soldier shown in Figure 19-7 was killed during

the Vietnam War when the jeep in which he was

riding was destroyed by a mine. The chest radiograph explains the scaphoid appearance of his abdomen: his stomach and much of his gut have herniated into the left hemithorax.

Rupture of the left hemidiaphragm accounts for

70% to 75% of these injuries, presumably because of

the shielding effect of the underlying mass of the

liver on the right.54 Traumatic diaphragmatic hernia may be discovered at the casualty’s initial

evaluation or incidentally at thoracotomy or

laparotomy performed for other reasons. The casualty may be asymptomatic or may present with respiratory distress. Patients with chronic rupture usually

present with symptoms of intestinal obstruction.

Diaphragmatic hernia is caused by three factors

in blunt trauma55:

1. The abdominothoracic pressure gradient

may exceed the usual maximum value of

100 cm H2O if the trauma patient gasps

against a closed glottis at the instant that a

large external force raises the intraabdominal pressure.
Anesthesia and Perioperative Care of the Combat Casualty

474

2. Thoracic compression during blunt trauma

distorts the anatomy of the diaphragm and

tears it with large shearing forces.

3. The trauma patient may have a congenital

weakness of the diaphragm.

The diagnosis of diaphragmatic trauma requires

a high degree of clinical suspicion by the military

anesthesiologist. Trauma to the diaphragm should

be suspected in casualties who have (a) injuries

below the fifth intercostal space and (b) injuries

associated with high-energy impact (eg, fractures

of the clavicles, upper ribs, scapulae, sternum, pelvis, or thoracolumbar spine). This condition must

be suspected when unexplained changes in pulmonary compliance occur intraoperatively in patients

who have sustained serious chest injury. Patients

with significant migration of viscera into the chest

cavity also appear to be at greater risk from aspiration pneumonitis. Postoperative difficulties in

b

a c

Fig. 19-6. This casualty presented with a

parenchymal lung laceration due to a perforating gunshot wound of the chest. (a) The

chest radiograph taken after insertion of a

chest tube shows that the damaged lung

remained collapsed. Although the chest tube

kinked, it was patent. This finding, in addition to the magnitude of the air leak and the

consequent difficulty of providing adequate

ventilation, constituted an indication for

thoracotomy. (b) A huge laceration was

found in the right upper lobe of the lung. A

lobectomy was performed. (c) The postoperative chest radiograph shows expansion of the

residual lung. Photographs: Swan Vietnam

Surgical Slide Collection.
Thoracic Injuries

475

a b

Fig. 19-7. (a) The external appearance of this dead soldier is notable for his scaphoid abdomen and his distended chest.

(b) The chest radiograph shows several transverse lines in the left hemithorax, which are caused by the walls of hollow

viscera that have herniated into the chest. The left diaphragm is not apparent. Massive displacement of the mediastinum

into the right hemithorax has occurred. Photographs: Wound Data and Munitions Effectiveness Team slide collection.

weaning a patient with thoracic trauma from mechanical ventilation should arouse suspicion of a

missed diaphragmatic hernia.

Operative positioning for the repair of a traumatic

diaphragmatic hernia depends on the side of the

injury and its chronicity. The more common left-side

hernia is best repaired through a laparotomy when

the diagnosis is made soon after the injury, and

when there is no evidence of a significant intrathoracic injury. Chronic left-side hernias are best treated

through a low posterolateral incision. Right-side hernias are nearly always repaired through a thoracotomy.

SUMMARY

Thoracic injuries in combat constitute 10% of the

surgical workload in wartime. Most of these injuries

are caused by penetrating missiles. In caring for

soldiers with such injuries, the military trauma anesthesiologist will encounter a paradoxical situation:

more often than not, it will be not the thoracic injury

itself but an injury to another body part that will be the

center of professional attention. The thoracic injury

can usually be managed by such simple interventions

as inserting a chest tube and debriding wounds.

In most cases in which thoracotomy is indicated,

it will be performed for control of (a) bleeding from

lacerated lung parenchyma or from the chest wall

and (b) air leaks from lacerated lung parenchyma.

Hemorrhage from a laceration, perforation, or rupture of the heart or great vessels will rarely be

encountered: such injuries are so rapidly fatal that

few casualties will survive long enough to reach a

medical treatment facility. If such a casualty does

arrive, the military trauma anesthesiologist may

be confronted with the need to resuscitate an agonal patient; from the practical standpoint, this

means being able to orchestrate an emergency thoracotomy.
Anesthesia and Perioperative Care of the Combat Casualty

476

Among the more severe intraoperative problems

likely to be seen by the military trauma anesthesiologist are (a) an air leak that is so massive that tidal volume

is inadequate, (b) airway obstruction due to accumulation of bloody secretions, and (c) systemic air embolism. These problems are best managed by selective

intubation of the bronchus of the uninjured lung.

Pulmonary contusion and flail chest are the two

treatment problems most likely to be seen in association with blunt trauma. Severe cases will require

intubation and mechanical ventilation. As a general rule, the military trauma anesthesiologist will be

most successful when treating a casualty with a thoracic injury if he or she prioritizes the many tasks at

hand in terms of the elementary ATLS principles of

airway, breathing, and circulation management.

REFERENCES

1. McNamara JJ, Messersmith JK, Dunn RA, Molot MD, Stremple JF. Thoracic injuries in combat casualties in

Vietnam. Ann Thor Surg. 1970;10:389–401.

2. Rosenblatt M, Lemer J, Best LA, Peleg H. Thoracic wounds in Israeli battle casualties during the 1982 evacuation

of wounded from Lebanon. J Trauma. 1985;25:350–354.

3. Beebe GW, DeBakey ME. Battle Casualties. Springfield, Ill: Charles C Thomas; 1952: 167, 181.

4. Bellamy RF, Zajtchuk R. The physics and biophysics of wound ballistics. In: Bellamy RF, Zajtchuk R, eds.

Conventional Warfare: Ballistic, Blast, and Burn Injuries. Part 1, vol 5. In: Zajtchuk R, Jenkins DP, Bellamy RF, eds.

Textbook of Military Medicine. Washington, DC: US Department of the Army, Office of The Surgeon General, and

Borden Institute; 1991: Chap 4.

5. Berry FB. General considerations of thoracic wounds. In: Berry FB, ed. Thoracic Surgery. In: Coates JB Jr, ed.

Surgery in World War II. Vol 1. Washington, DC: US Army Medical Department, Office of The Surgeon General;

1963: 59.

6. Viano DC, Lau IA. A viscous tolerance criterion for soft tissue injury assessment. J Biomechanics. 1988;21(5):387–399.

7. Viano DC. Live fire testing: Assessing blunt impact and acceleration injury vulnerabilities. Milit Med. 1991;156:589–595.

8. Suleman ND, Rasoul HA. War injuries of the chest. Injury. 1985;16:382–384.

9. Zakharia AT. Cardiovascular and thoracic battle injuries in the Lebanon War. J Thorac Cardiovasc Surg.

1985;89:723–733.

10. Thompson L. Former Lieutenant Colonel, Medical Corps, US Army. Personal communication, June 1991.

11. Brewer LA. Thoracoabdominal wounds. In: Berry FB, ed. Thoracic Surgery. In: Coates JB Jr, ed. Surgery in World

War II. Vol 2. Washington, DC: US Army Medical Department, Office of The Surgeon General; 1963: 101–136.

12. Bowen TE, Bellamy RF, eds. Emergency War Surgery NATO Handbook. 2nd rev US ed. Washington, DC: US

Department of Defense, Government Printing Office; 1988: 346–347.

13. Neal S. Medical Support of the US Army in Vietnam 1965–1970. Washington, DC: Department of the Army;

1973: 97–98.

14. Finucane BT. Thoracic trauma. In: Kaplan JA, ed. Thoracic Anesthesia. 2nd ed. New York, NY: Churchill

Livingstone; 1991: 463–484.

15. Kirsh MM. Acute thoracic injuries. In: Siegel J, ed. Trauma, Emergency Surgery and Critical Care. New York, NY:

Churchill Livingstone; 1987: 863.

16. Stene JK, Grande CM. Trauma Anesthesia. Baltimore, Md: Williams & Wilkins; 1991: 221, 226.
Thoracic Injuries

477

17. Duff JH, Goldstein M, McLean APH, et al. Flail chest: A clinical review and physiological study. J Trauma.

1968;8:63–74.

18. Symbas PN. Cardiothoracic Trauma. Philadelphia, Pa: WB Saunders; 1989: 344, 376–377.

19. Jones TB, Richardson EP. Traction on the sternum in the treatment of multiple fractured ribs. Surg Gynecol Obstet.

1926;42:283.

20. Moore BP. Operative stabilization of nonpenetrating chest injuries. J Thorac Cardiovasc Surg. 1975;70:619–630.

21. Fulton RL, Peters ET. Physiological effects of fluid therapy after pulmonary contusion. Am J Surg. 1973;126:773–778.

22. Meier GH, Symbas PN, Wood WJ. Systemic air embolism following penetrating lung injury. Ann Thorac Surg.

1979;27:161–169.

23. Symbas PN. Acute traumatic hemothorax. Ann Thorac Surg. 1978;26:195–196.

24. Kavolius J, Golocovsky M, Champion HR. Predictors of outcome in patients who have sustained trauma and

who undergo emergency thoracotomy. Arch Surg. 1993;128:1158–1162.

25. DiGiacomo JC, Odom JW, Swan KG, Salant M. Resuscitative thoracotomy and combat casualty care. Milit Med.

1991;156(8):406.

26. Yao ST, Vanecko RM, Printen K, et al. Penetrating wounds of the heart: A review of 80 cases. Ann Surg.

1968;168:67–78.

27. Trinkle JK, Marcos J, Grover FL, et al. Management of the wounded heart. Ann Thorac Surg. 1973;17:230–236.

28. Cassell P, Cullum P. The management of cardiac tamponade: Drainage of pericardial effusions. Br J Surg.

1967;54:620–626.

29. Proudfit WL, Effler DB. Diagnosis and treatment of cardiac pericarditis by pericardial biopsy. JAMA. 1956;161:188–192.

30. Guntheroth WG, Morgan BC, Mullins GL. Effect of respiration on venous return and stroke volume in cardiac

tamponade: Mechanism of pulsus paradoxus. Circ Res. 1967;20:381–390.

31. Fowler NO, Holmes JC. Hemodynamic effects of isoproterenol and norepinephrine in acute cardiac tamponade.

J Clin Invest. 1969;48:502.

32. Moseley RE, Vernick JJ, Doty DB. Response to blunt chest injury: A new experimental model. J Trauma.

1970;10:673–683.

33. Symbas PN. Cardiac trauma. Am Heart J. 1976;92:387–396.

34. Rea WJ, Sugg WL, Wilson LC, et al. Coronary artery lacerations—an analysis of 22 patients. Ann Thorac Surg.

1969;7:518–528.

35. Parmley LF, Manion WC, Mattingly TW. Nonpenetrating traumatic injury of the heart. Circulation. 1958;18:371–393.

36. Roberts WC, Maron BJ. Sudden death while playing professional football. Am Heart J. 1981;102:1062–1063.

37. Moritz AR. Trauma, stress and coronary thrombosis. JAMA. 1954;156:1306–1309.

38. Hillis LD, Braunwald E. Coronary artery spasm. N Engl J Med. 1978;299:695–702.
Abdominal Injuries

479

ROBERT G. KNIGHT, PH.D., M.D.*; AND RONALD F. BELLAMY, M.D.†

Chapter 20

ABDOMINAL INJURIES

INTRODUCTION

ABDOMINAL TRAUMA AND WAR SURGERY

Wound Ballistics

Diagnosis

Intraoperative Blood Salvage

PERIOPERATIVE CONSIDERATIONS

Antibiotics

Intravenous Access

Coexisting Disease and Monitoring

Induction of Anesthesia

Maintenance of Anesthesia

Nitrous Oxide

Positioning for Operation

SPECIFIC SITES OF ABDOMINAL INJURY

Retroperitoneal Injuries

Intraperitoneal Injuries

Damage Control

SUMMARY

*Formerly, Major, Medical Corps, U.S. Army; Assistant Director, Cardiothoracic Anesthesia, and Director, Anesthesia Research, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001; currently, Chairman, Department of Anesthesiology, Floyd Medical Center, Rome,

Georgia 30165

†Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

480

INTRODUCTION

Abdominal trauma is a frequent indication for

surgical exploration of the battlefield casualty.

During one 16-month period (1966–1967) of the

Vietnam War, 17,726 wounded American soldiers

were admitted to U.S. Army hospitals in Vietnam.

More than 70% of these injuries were due to small

arms, mines, artillery, or mortar fire. Approximately 14% of these soldiers had abdominal wounds,

which were frequently associated with wounds to

the head, chest, or extremities. One authority1 found

that during the Vietnam War, hospital mortality

was 4.5% in 2,454 casualties with abdominal wounds,

which compares favorably with mortality rates of

21% in World War II and 12% in the Korean War.

This reduction in mortality from abdominal

wounds is due to many factors, but undoubtedly

reflects the availability of rapid helicopter evacuation, improved understanding of the pathophysiology and treatment of hemorrhagic shock, improved antibiotic therapy, improved surgical

technique, and the availability of trained anesthesia personnel.

ABDOMINAL TRAUMA AND WAR SURGERY

reflect undiagnosed intraabdominal hemorrhage.

Similarly, an exploratory laparotomy for an abdominal wound may be suddenly accompanied

by wheezing, increased airway pressure, and arterial oxygen desaturation indicative of undiagnosed pneumothorax.

Myocardial laceration and cardiac tamponade

may also be associated with abdominal wounds.

Battlefield casualties with abdominal trauma who

reach the hospital level alive fall into two broad

categories: (1) a smaller group, who have life-threatening, exsanguinating hemorrhage; and (2) a larger

group, who are at risk of dying from sepsis due to

intestinal spillage. The former group will frequently

require urgent, if not emergent, surgery because of

the high potential for death; medical personnel can

take the time to perform thorough preoperative

resuscitations and evaluations with the latter group.

Israeli military surgeons made use of this distinction to treat abdominal casualties during the 1967

Yom Kippur War. Of 151 casualties who ultimately

required a laparotomy, 30 who were in shock on

arrival at the main field surgical hospital in the

Sinai underwent immediate operation. The remaining 121 casualties, all of whom were hemodynamically stable, were given intravenous fluids and antibiotics and then evacuated by air to Israel for

laparotomy. Mortality in the group who were operated on in the field was 20%, compared with 5% for

those who were operated on in Israel.2 By deploying far forward only enough medical assets to treat

the nontransportable casualties, the Israeli army’s

medical commanders markedly simplified the logistics of medical support.

If they recognize that most casualties do not

require immediate operation, medical officers can

avoid hurried preoperative evaluations, which may

overlook subtle findings indicative of serious

internal injury. Thus, it is important to remember that apparent chest wounds may penetrate

the abdominal cavity3 and abdominal wounds

may extend into the thoracic cavity (Figure 20-1).

Close attention must be paid to unexplained

hypotension in the apparently volume-resuscitated soldier undergoing thoracotomy, as it may

Fig. 20-1. Penetrating wounds to the chest may cause

serious injury to organs below the diaphragm, resulting

in a source of hemorrhagic shock not immediately apparent during thoracotomy. Penetrating abdominal wounds

may similarly enter the thoracic cavity through small

diaphragmatic perforations not readily seen during exploratory laparotomy.
Abdominal Injuries

481

The abdominal cavity is large and easily distended.4

It may contain large quantities of blood with no

readily apparent increase in circumference (Figure 20-2). A pelvic or retroperitoneal hematoma

may also hold several liters of blood. Retroperitoneal and pelvic hemorrhage may not be immediately apparent during exploratory laparotomy, and

should be considered when hypotension persists

after volume resuscitation. Another potential cause

of refractory hypotension is spinal shock: this diagnosis is suggested when hypotension is accompanied by bradycardia, strong pulses, and warm extremities in the presence of hemiplegia or

quadriplegia.

Wound Ballistics

The intraabdominal organs can be injured by

three mechanisms:

1. direct cutting and laceration, which are

caused by a penetrating projectile;

2. radial stretching and displacement, which

are caused by a penetrating projectile and

are the result of cavitation within the organ; and

3. crushing, which is caused by blast or blunt

trauma.

Most abdominal trauma in combat casualties is

caused by penetrating projectiles. Penetrating injuries that enter the peritoneal cavity may require

immediate exploration because of exsanguinating

hemorrhage. The path followed by a projectile

once it enters the abdomen generally follows a

straight line, but injury involving multiple organs is common.

Projectiles with high kinetic energy can cause

devastating injuries by the process of temporary

cavitation (ie, stretch). Tissues around the wound

tract are thrown aside with great force; the resultant

radial stretching and displacement can cause gross

disruption. Solid, friable organs such as the liver,

kidney, and spleen are especially susceptible to

injury by this mechanism (Figure 20-3).5 Hollow

organs such as the stomach, bowel, and bladder are

resilient and resist temporary cavitation if empty

but may be severely disrupted if distended with

fluid at the time of injury. Muscle withstands temporary cavitation with little permanent effect. As

might be expected, bone—markedly inelastic compared with muscle—may fracture when subjected

Fig. 20-2. The readily distensible abdominal cavity may hold large quantities of blood with minimal enlargement.

Adapted from Trunkey DD, Sheldon PF, Collins JA. The treatment of shock. In: Zuidemia PD, Rutherford RB, Ballinger

WF, eds. The Management of Trauma. 4th ed. Philadelphia, Pa: WB Saunders; 1985: 107.

AVERAGE 30 cm length 31 cm length 32 cm length

DIMENSIONS 12 cm radius 13 cm radius 14 cm radius

VOLUME Normal + 2.9 L + 6.1 L

CHANGE
Anesthesia and Perioperative Care of the Combat Casualty

482

made by the presence of one or more holes in the

trunk. One of the principles of military surgery is

that a laparotomy be performed whenever a penetrating projectile wound of the abdomen is found.

However, a hole in the abdominal wall is not necessarily synonymous with an intraabdominal injury,

and this principle—always operate—leads to the

occasional laparotomy that finds no evidence of

intraabdominal injury. The expected incidence is

approximately 20%.1

Because solid organs such as the liver, spleen,

and kidney are less able to dissipate kinetic energy

(ie, they are displaced and distorted) and maintain

their structural integrity, it is therefore not surprising that these organs are primary targets of

injury in blunt trauma.10–12 The decision to operate

following blunt trauma is frequently based on the

results of diagnostic peritoneal lavage (DPL).13 An

infraumbilical incision is made after local anesthesia is obtained, and 1 L of saline is introduced into

the abdominal cavity through a catheter. The saline

is then siphoned off. The following are indications

for exploratory laparotomy:

• gross blood or enteric contents in the

effluent,

• a red blood cell count greater than

l00,000/mm3,

• a white blood cell count greater than 500/

mm3,

• alkaline phosphatase greater than 3 international units,

• amylase greater than 20 international units,

or

• bile or bacteria in the effluent.

However, a computed tomography scan may be

needed for the preoperative diagnosis of retroperitoneal hematoma secondary to traumatic rupture of

the aorta or vena cava. In general, the sensitivity,

specificity, and predictive value of DPL is high in

both blunt and penetrating trauma.14 Computerized tomography complements the examination

when DPL is equivocal. Magnetic resonance imaging is highly accurate in defining tissue disruption

but is very time consuming; thus, it is impractical in

both the acute trauma setting15 and in third-echelon

surgical hospitals, as such equipment is not yet

fieldable.

Intraoperative Blood Salvage

Blood loss in combat casualties with intraabdominal trauma may be substantial. Data collected durFig. 20-3. An anesthetized swine was shot in the upper

abdomen from a distance of 3 m with a Russian AK74

(5.45 mm). Massive disruption and laceration of the liver

can be seen. The recovered, fired bullet was placed in the

center of the disrupted liver for comparison. Reprinted

from Fackler ML, Surinchak JS, Malinowski JA, Bowen

RE. Wounding potential of the Russian AK-74 assault

rifle. J Trauma. 1984;24(3):265.

to cavitation. (Weapons, the mechanisms of injury

to bone and soft tissue, the behavior of projectiles in

tissue, and cavitation phenomena are discussed in

Conventional Warfare: Ballistic, Blast, and Burn Injuries,

a volume in the Textbook of Military Medicine series.)6

The magnitude of temporary cavitation is greatly

increased by certain features of bullet construction:

fragmentation, as exemplified by rounds that are

fired by the M16 series of assault rifles; deformation, as is common with soft-point or hollownose bullets; and the bullet’s yaw and tumbling,

which are related to the location of the bullet’s

center of mass and the rate of spin imparted by

the rifling.7

Small, low-velocity fragments, in contrast to bullets fired by military small arms, do not produce

damage by cavitation. The clinical corollary of this

difference in behavior is that damage at a distance

from the wound path is to be expected with cavitating bullets but not with certain fragments or knives.

This is one of the reasons that some intraabdominal

knife wounds do not require surgical intervention.8,9

Diagnosis

The diagnosis of penetrating abdominal trauma

in combat casualties is quite straightforward, being
Abdominal Injuries

483

ing the Vietnam War indicate that approximately

37% of casualties with abdominal wounds required

blood transfusion, and the average amount of blood

administered was 8.9 units.16 In view of the extensive logistical demands posed by the transfusion

requirements, an approach using interoperative

blood salvage is clearly desirable. Equipment for

intraoperative blood salvage is now available in

some field hospitals and should be a valuable means

of reducing the need for homologous blood transfusion. A typical blood-salvaging device includes a

double-lumen tube that permits heparin to be added

to the blood as it is aspirated. The blood is then

pumped into a bowl, where it is washed with saline

and then centrifuged. The wash solution contains

surgical debris, white blood cells, platelets, and

clotting factors; it is discarded. Intact red blood

cells are concentrated to approximately 70% for

transfusion. A dedicated operator is required to

assemble the apparatus, select cycling parameters,

match the rate of heparin flow to the rate of blood

aspiration, and change solutions and waste collection bags. It is unlikely that a single anesthetist

involved in the resuscitation of a hemorrhaging

soldier will have the freedom from direct patient

care needed to fulfill this role; therefore, someone

other than an anesthesia provider will have to perform this procedure in field hospitals.

Intraoperative autotransfusion has been used

effectively in open heart, vascular, orthopedic, and

transplantation surgery.17 Its use in trauma surgery

has been limited.18 The potential for intestinal soilage of free intraabdominal blood is the particular

concern in abdominal surgery. Although the wash

cycle removes many bacteria, significant numbers

of anaerobes remain.19 Nevertheless, in the presence of life-threatening hemorrhage, blood that was

contaminated with intestinal contents, urine, and

bile has been reinfused.20 In deciding whether to

reinfuse contaminated blood, trauma anesthesiologists must consider the source of the blood (small

intestine vs. colon), the quantity of contamination,

and the urgency of transfusion. Similar concerns

arise when the wound has been irrigated with

Betadine Solution (povidone-iodine, manufactured

by Purdue Frederick, Norwalk, Conn.), antibiotics,

or any other substance not appropriate for intravenous use.

PERIOPERATIVE CONSIDERATIONS

pared to single-drug treatment using the semisynthetic penicillin mezlocillin (Mezlin, manufactured

by Miles Pharmaceutical, West Haven, Conn.), given

intravenously at a dose of 4 g every 6 hours.21

Likewise, a meta-analysis in which aminoglycoside combinations were compared with single βlactam antimicrobials showed no difference between the two therapies. 22 Military trauma

anesthesiologists who are assigned to deployable

hospitals should ascertain which available antibiotics are usable as single-drug prophylaxis in

casualties who have penetrating abdominal

trauma.

Intravenous Access

Perioperative considerations for the soldier with

abdominal trauma are similar to those for any other

type of trauma. Foremost is the need for adequate

intravenous access. Multiunit transfusions are common; replacement of two to three blood volumes

during the initial resuscitation is expected in 2% to

3% of patients.1,23 Adequate intravenous access is

thus imperative. During the Vietnam War, saphenous cutdowns were performed and intravenous

tubing was sutured directly into the vein, permitting very high rates of flow.24 Subclavian and interOnce the decision is made to perform a

laparotomy, the most important consideration regarding the casualty is whether there are injuries to

other body parts that will be treated simultaneously

by multiple operating teams. After this determination has been made, the following interventions

must be considered.

Antibiotics

The military trauma anesthesiologist must ensure that the combat casualty with a penetrating

intraabdominal injury receives antibiotics as soon

as possible. In the past, appropriate therapy consisted of an aminoglycoside for Gram-negative coverage and one or two additional drugs to combat

Gram-positive and anaerobic organisms. However,

because of potential nephrotoxicity from aminoglycoside, interest has been shown in developing singledrug regimens, usually employing a semisynthetic

penicillin or cephalosporin, to be administered to

patients with penetrating abdominal trauma. No

difference in the rate of infectious complications

was found in one study in which a conventional

regimen (clindamycin 600 mg, administered every

6 h, and gentamicin 80 mg, administered every 8 h,

adjusted for body size and renal function) was com-
Anesthesia and Perioperative Care of the Combat Casualty

484

nal jugular venous access has also found recent

utility.25 With these options available, little time

should be spent searching for peripheral access in a

patient with extreme vasoconstriction secondary to

hemorrhagic shock.

Coexisting Disease and Monitoring

Unlike their civilian counterparts, the victims of

battlefield trauma usually have no underlying disease. Although it is beneficial in hemorrhagic shock,

invasive monitoring of arterial and central venous

pressure contributes little to the eventual outcome

of soldiers undergoing resuscitation and massive

transfusion. Clinical signs of capillary perfusion,

jugular distension, the quality of the pulse, urinary

output, and the requirement for anesthetics are

excellent indices of the adequacy of volume resuscitation of young, healthy soldiers.26 If sufficient

personnel and equipment are available, invasive

monitoring is not contraindicated if it does not

delay control of hemorrhage.

Induction of Anesthesia

Wounded soldiers with abdominal trauma may

be intubated awake or with a rapid-sequence induction. In wartime, the rapid sequence is frequently

performed—not because it is superior but because

of the high demand for rapid turnover of the operating room. Either ketamine or sodium thiopental

may be used for induction, but using a dosage appropriate to the patient’s condition is of more importance

than the particular anesthetic selected. A moribund

patient requires no anesthetic, just succinylcholine

to ensure muscle relaxation prior to intubation. An

alert patient with a profound volume deficit requires correspondingly less anesthetic than an volume-replete patient. As little as 0.25 mg of ketamine

or sodium thiopental per kilogram of body weight

may be all that is necessary to produce unconsciousness in the hypovolemic patient. There are

two reasons for this:

1. The anesthetic is diluted in a smaller total

blood volume.

2. In the hypovolemic state, a much larger

proportion of the cardiac output is delivered to the brain and heart.

Both these factors produce a higher content of anesthetic in these organs than might be expected from

the reduced cardiac output characteristic of shock.

The key to the successful anesthetic management of

the trauma patient is the use of reduced and fractionated dosages of any medication given.

Maintenance of Anesthesia

Maintenance of anesthesia may consist of (a)

continued incremental dosages of ketamine, (b) small

dosages of narcotics, and (c) benzodiazepines or

potent inhalational agents, as tolerated. The requirement for potent inhalational agents for

nontraumatized euvolemic patients is usually described in terms of the minimal alveolar concentration (MAC), which prevents purposeful movement

in response to a surgical stimulus in 50% of the

patient population tested.27 Several factors that

reduce MAC may be present in the trauma patient,

including hypothermia, hypoxia, severe anemia,

and hypotension.28 Hemorrhage ultimately produces all four of these conditions, so it is not surprising that the hemorrhaging patient will require

less inhalational agent. The reason for this includes

the previously discussed fact that with hemorrhage,

a larger proportion of the cardiac output is delivered to the brain and the heart, and so the anesthetic

partial pressures in these organs rise quickly. Additionally, blunting of sympathetic tone by anesthetics rapidly manifests as life-threatening

hypotension. The trauma anesthesiologist can compensate for these responses by using fractional values of MAC as tolerated by the patient’s blood

pressure.

However, the tenuous balance between preserving an adequate blood pressure and ensuring anesthesia is difficult to maintain, as fluid and anesthetic requirements fluctuate widely during surgery.

Lower partial pressures of anesthetic do not ensure

lack of awareness; recall of intraoperative events is

not uncommon in the trauma patient.29

The anesthetic partial pressure that prevents patient movement is not necessarily the same partial

pressure that prevents intraoperative awareness or

postoperative recall. For example, in a normovolemic patient, hypnosis is produced by fractions

of MAC. The alveolar concentration of anesthetic at

the time patients first open their eyes in response to

verbal command during recovery from anesthesia

is known as MAC-awake. For isoflurane, MACawake has been reported to be 0.19%, or 15% of

MAC.30 MAC-awake for other inhaled anesthetics

has been reported to be 33% to 50% of MAC.31 Most

patients who are maintained on end-tidal concentrations of potent, inhaled anesthetics in this range

do not recall intraoperative events. Conversely,

there are case reports describing recall with appar-
Abdominal Injuries

485

ent (but not measured) end-tidal concentrations

exceeding these values.32,33 The extent to which

hemorrhage reduces MAC-awake has not been determined, but anesthesiologists can take some comfort from knowing that low concentrations of potent inhaled anesthetics produce amnesia in the

normovolemic patient.

Nitrous Oxide

The use of nitrous oxide in the battlefield casualty with abdominal trauma deserves special mention. Since World War I, nitrous oxide has been an

extremely valuable adjunct to the anesthetic care of

the battlefield casualty.23,25,34,35 Although nitrous

oxide is not able to provide a complete anesthetic

for the normovolemic patient undergoing elective

surgery, it is excellent in preserving cardiovascular

stability in many trauma patients. However, even

nitrous oxide is not always tolerated by the most

seriously wounded.35

Nitrous oxide is notorious for producing gaseous

distention of the gut in the absence of bowel obstruction, and is therefore clearly contraindicated

in the presence of a closed air space (eg, pneumothorax, pneumocephalus, bowel obstruction). That

nitrous oxide diffuses into closed spaces more rapidly than relatively insoluble gases (eg, methane,

hydrogen, nitrogen) diffuse out is unquestioned.

Rather, the argument has been made that these

gases are present in the gastrointestinal tract in

small volumes and are thus insignificant even if

their volume is increased 2- or 3-fold.36 However,

recent studies have demonstrated significant differences in qualitatively assessed gas content of

the small and large bowel, and operating conditions

of patients given nitrous oxide, compared with air,

as part of their anesthetic for bowel surgery (Figure 20-4).37 Additionally, return of bowel function

and duration of hospital stay were shorter for patients not given nitrous oxide. Although not all

patients given nitrous oxide had bothersome distention of the bowel by the end of surgery (the

average duration of anesthesia was 282 ± 53 min),

the evidence clearly favors the use of air rather than

Fig. 20-4. A casualty’s small bowel during a laparotomy

for a fragment wound of the abdomen. The anesthetist

ascribed the distension of the small bowel to the presence

of nitrous oxide. Photograph: Swan Vietnam Surgical

Slide Collection.

Data from the Wound Data and Munitions Effectiveness Team (WDMET) database, which was compiled during the Vietnam War, indicate that about

50% of casualties with an abdominal wound who

survived long enough to reach a hospital had an

injury to a single intraabdominal organ. The most

SPECIFIC SITES OF ABDOMINAL INJURY

commonly injured organs were large bowel including the rectum in 23% of these casualties, small

bowel also in 23%, and liver in 14%. In casualties

with injuries to multiple intraabdominal organs,

30% had an injury to two organs, 13% to three, 4% to

four, and 3% to five or more organs.38 The most

nitrous oxide during bowel surgery of this duration. When considered with the logistical demands

of supplying compressed gases in the field environment, it may be that nitrous oxide is best avoided

in the battlefield casualty undergoing abdominal

surgery. For reasons such as these, nitrous oxide

has been deleted from the U.S. Department of

Defense’s Deployable Medical Systems (DEPMEDS)

list.

Positioning for Operation

Because a midline incision is the standard for a

laparotomy on combat casualties, the supine position will be needed. Casualties in refractory shock

may first be subjected to a thoracotomy, but this

will usually be done through an anterolateral incision with the casualty in the supine position.

Debridement should be performed prior to

laparotomy in hemodynamically stable casualties

who have multiple wounds, some of which involve

the dorsum of the trunk, or a large wound of exit or

entrance posteriorly. Thus, these casualties should

initially be placed in either the prone or the lateral

decubitus position.
Anesthesia and Perioperative Care of the Combat Casualty

486

common combinations in casualties with injuries

to multiple organs were small bowel and colon;

small bowel and liver; and small bowel, colon,

and stomach.

Because casualties with injuries to multiple organs are common, a systematic approach is essential to avoid missing an important site. A wide

range of severity will be encountered and the severity influences how the injury is managed. To bring

clarity to discussions of abdominal trauma, the severity of injury has been scaled for each organ.39,40

Although this system of injury severity classification has not yet been applied to combat casualties,

military anesthesiologists need to know how to use

it. In general, for any given organ, two broad

classes of injuries are recognized: hematoma (more

often than not indicating blunt trauma) and laceration (usually indicating penetrating trauma). For

each type of injury, five or six grades of severity are

recognized and in turn are correlated with the International Classification of Disease (ICD-9) and the

Abbreviated Injury Scale (AIS). As an example, the

scheme as it applies to the liver is reproduced in

Table 20-1. Figure 20-5 shows a casualty from the

Vietnam War with a grade III laceration caused by

fragments from a Claymore mine.

Retroperitoneal Injuries

The retroperitoneum contains major blood vessels (aorta, inferior vena cava) as well as the kidneys, ureters, pancreas, and duodenum. Any of

these sites may be involved in penetrating or blunt

trauma if the vector of injury is of significant magTABLE 20-1

CLASSIFICATION OF SEVERITY OF HEPATIC INJURY

Grade* Injury Description† ICD-9 AIS 90

I Hematoma Subcapsular, nonexpanding, < 10% surface area 864.01 2

864.11

Laceration Capsular tear, nonbleeding, < 1 cm parenchymal depth 864.02 2

864.12

II Hematoma Subcapsular, nonexpanding; 10%–50% surface area 864.01 2

Intraparenchymal, nonexpanding; < 2 cm in diameter 864.11

Laceration Capsular tear, active bleeding; 1–3 cm parenchymal depth, < 10 cm 864.03 2

in length 864.13

III Hematoma Subcapsular, < 50% surface area or expanding 3

Ruptured subcapsular hematoma with active bleeding;

Intraparenchymal hematoma > 2 cm or expanding

Laceration > 3 cm parenchymal depth 864.04 3

864.14

IV Hematoma Ruptured intraparenchymal hematoma with active bleeding 864.04 4

Laceration Parenchymal disruption involving 25%–50% of hepatic lobe 864.14 4

V Laceration Parenchymal disruption involving > 50% of hepatic lobe 5

Vascular Juxtahepatic venous injury (ie, retrocaval vena cava/major 5

hepatic vein)

VI Vascular Hepatic avulsion 6

* Advance one grade for multiple injuries to the same organ

† Based on most accurate assessment at autopsy, laparotomy, or radiological study

ICD-9: International Classification of Disease, 9th revision; AIS 90: Abbreviated Injury Scale, 1990 revision

Adapted with permission from Moore EE, Shackford SR, Pachter HL, et al. Organ injury scaling: Spleen, liver, and kidney. J Trauma.

1989;29:1665.
Abdominal Injuries

487

nitude and direction. Isolated retroperitoneal injuries from penetrating missiles are unusual, because

the missile usually passes from the retroperitoneal

space into the abdominal cavity.

To assist in deciding on the optimal intraoperative

intervention, it has become customary to divide the

retroperitoneum into three zones41:

• Zone 1: midline to midclavicular lines (includes the great vessels and most of the

duodenum and pancreas);

• Zone 2: from midclavicular lines laterally

to the flanks (includes the kidneys); and

• Zone 3: below the iliac crests (includes the

iliac vessels).

At the hospital level, Zone 3 injuries are encountered most commonly. Zone 1 injuries are least

common, probably because injuries to Zone 1 frequently result in rapid exsanguination. Penetrating

injuries are explored regardless of the zone. Blunt

trauma involving Zone 1 is always explored, as is an

enlarging hematoma in Zone 2. Exploration of a

hematoma in Zone 3 should be avoided.

Great Vessels

Analysis of the WDMET database reveals that

isolated injuries to the great vessels (the aorta, iliac

arteries, and inferior vena cava) account for about

one half of all deaths of combat casualties who were

killed in action or died of intraabdominal injuries

(see Chapter 1, Combat Trauma Overview, for a

discussion of the WDMET database).38 Intraabdominal injuries to the great vessels are very uncommon

in combat casualties who survive; for example, there

are only eight survivors of intraabdominal aortic

injuries in the Vietnam Vascular Registry.42 Nevertheless, the military anesthesiologist should be prepared for such a contingency. A midline retroperitoneal hematoma may reflect injury to the aorta or

vena cava and should be explored. Although arterial injury is associated with more-rapid blood loss,

venous injury, which is characterized by low-pressure but high-volume hemorrhage, frequently

proves more difficult to control. Furthermore, attempts to define the anatomy of vena caval injury

by occlusion may precipitate cardiac arrest in the

hypovolemic patient. Atrial–caval or femoral–caval

shunts have been suggested (but in fact are rarely

employed) to maintain circulation while vascular

clamps are applied to isolate the site of hemorrhage,

but these techniques have not been demonstrated to

improve survival. Injuries to the retroperitoneal

vasculature carry a high mortality,43,44 and lacerations of the retrohepatic vena cava are particularly

lethal.45

Kidneys, Ureters, and Bladder

The kidneys, ureters, and bladder may be injured

directly by projectiles or indirectly by blunt trauma.

Blunt trauma, or the cavitary damage accompanying high-energy-transfer projectiles, may produce

avulsion of the renal vascular pedicle, fracture of

the renal parenchyma, or avulsion or disruption or

both of the ureters. The elasticity of the bladder

renders it less susceptible to disruption46 and, more

commonly, the injury results from direct cutting by

the missile. These injuries may be revealed

Fig. 20-5. This injury was caused by a fragment from an exploding munition. (a) The wound of entrance is in the dome

of the lateral segment of the right lobe of the liver. This is a grade III laceration of the liver. (b) The wound of exit is

in the undersurface of the right lobe of the liver. Photographs: Swan Vietnam Surgical Slide Collection.

a b
Anesthesia and Perioperative Care of the Combat Casualty

488

preoperatively by computed tomography scan, intravenous pyelogram, retrograde pyelogram, ultrasound, or, as is common in combat casualties, may

be discovered incidentally during laparotomy.47 In

the latter situation, it is essential that an effort be

made to demonstrate the presence of a functioning

contralateral kidney before ablative renal surgery is

undertaken. One way to do this is to clamp the

ureter on the injured side and watch the Foley

catheter for 5 minutes to see if urine continues to be

formed. Ureteral injuries are difficult to diagnose

except by direct visualization at the time of

laparotomy.

Relatively minor degrees of renal trauma resulting from blunt trauma are managed nonsurgically.

The diagnosis of renal injury associated with penetrating missiles is usually made at the time of

laparotomy. Knowing exactly what to do about

grade II (< 1-cm parenchymal depth of renal cortex

without urinary extravasation) or grade III (> 1-cm

parenchymal depth of renal cortex without collecting-system rupture or urinary extravasation) injuries is difficult and controversial. Treatment options are partial nephrectomy, debridement, and

suture. Grade IV injuries (laceration extending

through the cortex, medulla, and collecting system;

or a major renal vessel injury) or grade V injuries

(completely shattered kidney) are treated in combat

zone hospitals by nephrectomy (Figure 20-6). Renal

function declines more in patients who are managed operatively; whether this is due to the effects

of surgery itself or the presence of more -underlying

tissue destruction is unknown.48,49

Injuries to the dome of the bladder are often easy

to repair because the remaining wall is usually

sufficiently redundant to be closed primarily. Care

must be taken to ensure that the ureteral orifices are

not compromised during closure of the defect. The

bladder is closed over a Foley catheter; ureteral

injuries are closed over a ureteral catheter splint.

Injuries to the trigone of the bladder that require

reconstruction may require reconstruction of both

the urethra and the ureteral orifices.

Pancreas and Duodenum

Blunt pancreatic injuries are difficult to detect

with peritoneal lavage and may be missed by computed tomography scan. Elevated amylase in the

lavage fluid from DPL raises suspicion but is neither sensitive nor specific: the absence of amylase

does not exclude significant pancreatic injury, and

its presence may only reflect small bowel or urinary

tract injury.50 Serum amylase should be measured

serially if the site of injury leads to a suspicion of

pancreatic damage. Severe pancreatitis will result

if pancreatic enzymes are not contained within the

pancreatic ducts, so careful, regular consideration

must be given to this diagnosis when the physical

examination and test results are equivocal.

Grades I or II pancreatic injuries (laceration without duct injury or tissue loss) resulting from penetrating trauma require only closed-suction drainage. More-severe pancreatic injuries such as a

disrupted tail or distal ductal laceration (grade III)

may be treated by distal pancreatectomy. Injuries

of the head of the pancreas, especially when the

ampulla or duodenum are involved (grades IV or V)

may be treated with the Whipple procedure

(pancreaticoduodenectomy with gastrojejunostomy

and Roux-en-Y cholecystojejunostomy and Rouxen-Y pancreaticojejunostomy). Mortality is 30% to

40%.51 The difficulty, complexity, and time-consuming nature of the Whipple procedure makes it

unsuitable for performance in the combat zone except in unusual circumstances.

Isolated duodenal injuries are treated by closure

of the defect, sometimes in conjunction with temporary defunctionalization of the duodenum brought

about by closure of the pylorus with absorbable

suture material. A gastrojejunostomy is constructed

to reestablish gastrointestinal continuity. The pyloric suture can be expected to remain intact until

the duodenal defect is securely healed. Severe

injuries, especially when they involve the head of

the pancreas, may require a Whipple procedure;

however, an operation of such magnitude may severely disrupt the function of a forward surgical

facility and should be performed only as a last

resort. Dependent drainage is a necessary part of

any duodenal or pancreatic operation.52 Repeated

surgeries are often required for treatment of pancreatic fistulas, abscesses, secondary hemorrhage,

and pseudocysts. Catastrophic shock occurs in

those few who develop hemorrhagic pancreatitis.

Intraperitoneal Injuries

For military anesthesia providers, the major treatment problems of casualties with abdominal injuries involve the intraabdominal organs, which contaminate the abdomen and give rise to peritonitis.

To a lesser extent, hemorrhage is a threat; regrettably, however, most casualties who have significant

intraabdominal vascular injuries will have exsanguinated before they reach the hospital. Two
Abdominal Injuries

489

a b

c d

e

Fig. 20-6. (a) This grade IV kidney injury to a casualty during the Vietnam War was caused by a large mortar fragment

and was treated by a nephrectomy. The wound of entrance is in the casualty’s back. (b) Grossly bloody urine was found

in the casualty’s bladder, indicating a significant injury somewhere in the urinary tract. (c) Anteroposterior and (d)

lateral radiographs taken during an intravenous pyelogram. A large metal fragment is seen in the left upper quadrant

of the abdomen. There is no evidence of function by the left kidney. (e) The upper pole of the kidney appears cyanotic,

a finding indicating a vascular injury. This was the indication for a nephrectomy, which is shown in progress. (f) The

excised kidney and the fragment that caused the injury. Photographs: Swan Vietnam Surgical Slide Collection.

casualties of the Vietnam War who were seen at

the hospital level of care illustrate the ramifications of penetrating abdominal trauma (Figures 20-7 and 20-8). Note that in both casualties,

the retroperitoneal component of the injury is the

less serious.

Stomach, Small Bowel, and Colon

Injuries to the stomach, small bowel, and colon

are accompanied by hemorrhage and peritoneal

contamination. Bacterial peritonitis may result from

spillage of the stomach contents into the peritoneal

f
Anesthesia and Perioperative Care of the Combat Casualty

490

a b

c d

Fig. 20-7. (a) This soldier sustained a perforating AK47 (7.62-mm) bullet wound of the inferior portion of the right lower

quadrant of his abdomen. The wound of entrance is shown. A second bullet wound in the thigh involved only soft

tissue. (b) The bullet exited from the flank, causing an evisceration. (c) At laparotomy, the tip of the cecum was found

to be perforated. The casualty underwent a cecostomy in lieu of an ileotransverse colostomy. (d) The casualty’s

multiple small bowel perforations were treated by small bowel resection and anastomosis. Photographs: Swan

Vietnam Surgical Slide Collection.

cavity if a meal has recently been ingested, or, as is

common in battle casualties, if stomach emptying is

delayed. Salivary flora are ingested during a meal

and bacterial counts rise rapidly as stomach acidity

is neutralized. As the stomach empties, the hydrogen ion concentration again falls to bactericidal

levels, rendering the stomach sterile.53 Penetrating

injury to the stomach is usually managed easily by

primary suture. The stomach’s good blood supply

assures primary healing. With any wound of the

Fig. 20-8. This soldier sustained a perforating AK47 (7.62-mm) bullet wound of the lower abdomen. (a) The wound of

entrance is seen in the right buttock. Proctoscopy demonstrated blood in the rectum, indicating an injury to the distal

large intestine. (b) The wound of exit is in the left lower quadrant of the abdomen. The bullet apparently passed

posterior to the right iliac vessels and anterior to the left iliac vessels, thereby sparing the casualty from death due to

exsanguination. (c) The massive small bowel damage can be seen at laparotomy. (d) The shredded appearance of this

resected specimen of small bowel is probably caused by temporary cavitation, which occurred as the bullet passed

through the fluid- and gas-filled viscera. (e) The bladder was totally disrupted by the bullet. (f) Because of the

proximity of the damage to the trigone of the bladder, safe reconstruction of the bladder required catheterization of

both ureters and the urethra. The balloon of the urinary catheter is seen in the depth of the wound. (g) The rectosigmoid

colon has been perforated by the bullet. A totally diverting end colostomy and a mucus fistula are being constructed.

(h) The casualty is now in the prone position. The perirectal space is exposed for purposes of drainage. Photographs:

Swan Vietnam Surgical Slide Collection.
Abdominal Injuries

491

a b

c d

e

g h

f
Anesthesia and Perioperative Care of the Combat Casualty

492

stomach, it is important to determine whether the

projectile continued through the posterior wall into

the lesser sac and the retroperitoneum.

The small bowel has a very low bacterial count,

but peritonitis will eventually occur as the bacteria

proliferate. Grades I and II injuries (partial-thickness and full-thickness wounds involving less than

one half the bowel circumference) are managed by

primary suture repair of the defect. Grade III injuries (defects of > 50%) and grade IV injuries

(transection) are managed by resection and primary anastomosis. Multiple, contiguous grade II

injuries are best managed by resection and anastomosis.

Colon wounds are difficult to manage: primary

healing of a sutured colon wound, in contrast to a

wound of the small bowel, has a disturbingly high

rate of failure. The peritoneal cavity is capable of

tolerating one episode of exposure to the vast bacterial population that resides in the colon, but continued contamination, as will occur with a suture-line

breakdown, is rapidly lethal. The following scenario is much feared by military surgeons: a

casualty’s colonic wound is primarily repaired in a

forward surgical hospital; the wound then dehisces

during evacuation; and by the time the casualty

reaches the next hospital, he is dying from fulminating peritonitis. To prevent this occurrence, military

surgical doctrine dictates that a proximally diverting colostomy be constructed on all casualties with

large bowel injuries. This practice is at variance

with civilian trauma management, in which primary repair is frequently possible.

In grades I, II, or III colonic injuries, primary

repair of the colonic wound may prove possible, but

the colostomy will assure that the segment is

defunctionalized so that leakage of colonic contents, if it occurs, will be inconsequential. Resection

is indicated when the projectile transects the bowel

(grade IV) or destroys a segment (grade V). The

colon distal to the site of resection is mobilized so

that it can be pulled through the abdominal wall as

a mucous fistula.

Injuries to the rectum create special problems

because of the need to both evacuate all feces from

the retained bowel and drain the perirectal space in

the perineum. Therefore, the casualty with a rectal

wound will have a proximally diverting colostomy,

a distal mucous fistula (or a closed intraabdominal

segment known as a Hartmann’s pouch), and an

excised coccyx through which drainage of the perirectal

space is established. To accomplish this sequence of

procedures, the anesthesiologist must be prepared to

turn the casualty from supine to prone.

Liver

Hepatic trauma is commonly encountered in abdominal wounds. Grades I and II injuries are rarely

the sole cause of death and require no surgical

intervention at the time of laparotomy.54 Grades III

and IV injuries are more difficult to treat: suture

ligation of vessels will be necessary to control bleeding. Grade V injuries can be treated by formal right

or left hepatic lobectomy, but not only is the mortality of this intervention extremely high (not a single

casualty subjected to a right hepatic lobectomy in

the Vietnam War is thought to have survived), the

demands for blood and blood products will likely

exhaust all but the largest blood bank. As an alternative to lobectomy, the practice dating from World

War II of tamponading the bleeding liver by packing with large laparotomy pads has been proposed.

The pack must be removed within 2 to 4 days.55 The

goal is to remove the packs safely after the casualty

has reached a higher-echelon medical treatment

facility that is capable of providing care of the

needed sophistication.

The overwhelming problems that will encountered by the anesthesiologist caring for a casualty

with a grade IV or V liver injury will be massive

hemorrhage and its complications (hypothermia,

acidosis, hypocalcemia, coagulopathy, and the adult

respiratory distress syndrome). Intraoperative hemorrhage in these patients may be controlled by the

Pringle maneuver (ie, manual compression of the

porta hepatis at the epiploic foramen). If this fails,

occlusion of the thoracic aorta or the proximal abdominal aorta may be attempted. The most difficult

bleeding to control is from a vascular injury at the

junction of the hepatic veins with the inferior vena

cava. The problem arises from the fact that exposure of the site of injury is possible only when the

inferior vena cava is occluded, but the resulting

cessation of venous return usually precipitates a

cardiac arrest in the already hypovolemic casualty.

In rare circumstances, surgeons have been able to

shunt blood from the infrahepatic vena cava to the

heart, using a plastic tube with a large tangential

port (an endotracheal tube can be so modified)

inserted through the right atrial appendix and from

there guided into the vena cava below the liver.

Tourniquets are then tightened around the

supradiaphragmatic and infrahepatic venae cava.56

By isolating the liver and its blood supply, exposure

is facilitated and transfusion requirements are reduced. An extension of the shunt may be passed to

the anesthesiologist, who then uses it for transfusion. Blood glucose should be closely monitored, as
Abdominal Injuries

493

hypoglycemia is not uncommon. Casualties with

grades IV or V liver injuries will frequently need

secondary operations for removal of a hepatic pack,

further debridement, and drainage of hematomas

or abscesses or both.57

Spleen

For many years, the spleen was considered to be

a vestigial organ of no significance and was treated

as such in abdominal trauma. Since the 1950s,

however, the spleen has come to be recognized as a

key component of the immune system. The risk of

early or delayed infection is increased in asplenia.

Overwhelming postsplenectomy infection occurs

in about 0.6% of children and 0.3% of adults.58 As a

result, in civilian practice, the options for managing

splenic injury emphasize conservation whenever

possible. The options are (a) application of a topical

hemostatic agent, (b) debridement and suturing,

and (c) splenectomy, which is reserved as a last

resort. Wrapping the spleen with an absorbable

mesh bag has proven valuable in treatment of extensive capsular avulsion.59 Grades I, II, and III

injuries (ranging from slight capsular tear to parenchymal laceration not involving the hilum) in blunt

trauma have been managed nonoperatively when

hemodynamic instability and other organ involvement are absent (in the field, however, this can be

established with certainty only at the time of

laparotomy).60

Although splenic conservation is desirable, such

an approach has little merit in the management of

combat casualties: the essential condition for its

application is time to observe the casualty, and this

is precisely what cannot be guaranteed in a combat

zone hospital. Furthermore, the specter of delayed

hemorrhage during evacuation is too frightening to

ignore. Accordingly, splenectomy remains the accepted treatment for combat casualties with all but

grade I injuries. As is standard with civilian postoperative management of patients who have had

splenectomy, antipneumococcal vaccine should be

given, and the casualty should be warned of the

possible implications of high fever in association

with an infection.

Diaphragm

The diaphragm may be ruptured in blunt trauma

or perforated in penetrating trauma. In either case,

intraabdominal organs may herniate through the

diaphragm and produce respiratory embarrassment

or organ strangulation. Unless the diaphragm is

carefully inspected at the time of laparotomy, a

perforation can be missed until clinical symptoms

or an abnormal chest radiograph provoke further

study.61–63 Even a small perforation needs to be

closed because the defect will gradually enlarge

and become the site of a potentialy fatal herniation.

Holes in the diaphragm can also create problems for

the anesthesiologist during the operation because

air can pass from the open abdomen into the chest,

creating a pneumothorax. A chest tube placed

preoperatively will prevent this condition; however, the surgical team must remember that a missile wound in the area of the costal margin may first

have passed through the pleural space and diaphragm before entering the abdomen.

The advent of endoscopic laparotomy is certainly

the most significant development in modern gastrointestinal surgery, but the practicality of

laparoscopy as a therapeutic modality for treating

typical combat injuries in deployed hospitals is

unclear. Both endoscopic thoracoscopy and

laparoscopy in a diagnostic mode have been used to

demonstrate penetrating diaphragmatic injury.64 A

thoracic endoscopic approach to diagnosing diaphragmatic injury (and by implication, a possible

intraabdominal injury) following a missile wound

to the lower thorax would appear to be a reasonable

alternative to observation or an exploratory

laparotomy. If a hole in the diaphragm is seen, a

laparotomy is indicated both to close the hole and to

treat any coexisting intraabdominal injuries.

Damage Control

The concept of staging the operative interventions

in the severely injured to allow for optimizing the

casualty’s physiological status is known by a variety

of names: “abbreviated laparotomy and planned

reoperation,”65 “staged celiotomy,”66 and “delayed

gastrointestinal reconstruction,”67 among others. What

these terms describe is the following sequence:

1. emergency laparotomy performed to stop

exsanguinating hemorrhage and to prevent

further peritoneal contamination;

2. a nonoperative resuscitative phase during

which hypovolemia, hypothermia, acidosis, and coagulation defects are corrected;

and

3. repeat laparotomy to definitively correct

the injuries.

The essential feature of this regimen is the “damage control” of the life-threatening injuries that are
Anesthesia and Perioperative Care of the Combat Casualty

494

found during the initial laparotomy: enteric injuries are ligated to prevent further peritoneal contamination, and exsanguinating hemorrhage is controlled by clamping or packing. Because of its

staged nature, this regimen would appear to have

much to offer military surgery, which is, after all,

characterized by the provision of care by stages, or

echelons. We can imagine a forward surgical team

performing the initial laparotomy, and then the

casualty’s being immediately evacuated to a thirdechelon hospital for resuscitation and definitive

surgery. However, this regimen should be considered for use only if rapid and reliable evacuation can be

guaranteed.

SUMMARY

Abdominal injuries are the most common lifethreatening injuries that military anesthesia providers are likely to encounter. Casualties with

abdominal injuries may present with exsanguinating hemorrhage, but more commonly, a stable

patient will present with intraabdominal contamination as the major threat to life. with intraabdominal contamination. In the former circumstance,

military anesthesia providers will strive for adequate oxygenation, with fluid resuscitation ongoing during surgical control of hemorrhage. In the

latter circumstance, a more measured and thorough

approach to preoperative preparation is usually

possible. In the ideal circumstance, the casualty

will receive adequate fluid resuscitation, intravenous antibiotics, and instrumentation for monitoring. Although operations have been done using

regional anesthetic techniques, the overwhelming majority are best managed using endotracheal

anesthesia.

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38. The single most useful database describing combat wounds and the circumstances of wounding is the Wound

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the Vietnam War. These data are stored at the National Naval Medical Center, Bethesda, Maryland. Access is

controlled by the Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799;

telephone (301) 295-6262. Three summary volumes contain extensive abstracts of the statistical data and can be

obtained from Defense Documentation Center, Cameron Station, Alexandria, Virginia 22304-6145; telephone

(703) 545-6700 and (703) 274-7633.

39. Moore EE, Shackford SR, Pachter HL, et al. Organ injury scaling, I: Spleen, liver, and kidney. J Trauma.

1989;29:1664–1666.

40. Moore EE, Cogbill TH, Malangoni MA, et al. Organ injury scaling, II: Pancreas, duodenum, small bowel, colon,

and rectum. J Trauma. 1990;30:1427–1429.

41. Selivanov V, Chi HS, Alverdy JC, Morris JA Jr, Sheldon GF. Mortality in retroperitoneal hematoma. J Trauma.

1984;24:1022–1027.

42. Spencer F, Rich N. Vascular Trauma. Philadelphia, Pa: WB Saunders; 1978: 339.

43. Kudsk KA, Sheldon GF, Lim RC. Atrial–caval shunting (ACS) after trauma. J Trauma. 1982;22:81–85.

44. Collins PS, Golocovsky M, Salander JM, Champion H, Rich NM. Intra-abdominal vascular injury secondary to

penetrating trauma. J Trauma. 1988;28:S165–170.

45. Buechter KJ, Sereda D, Gomez G, Zeppa R. Retrohepatic vein injuries: Experience with 20 cases. J Trauma.

1989;29:1698–1704.

46. O’Connell KJ, Clark M, Lewis RH, Christenson PJ. Comparison of low- and high-velocity ballistic trauma to

genitourinary organs. J Trauma. 1988;28(suppl):139–144.

47. Bretan PN, McAninch JW, Federle MP, Jeffrey RB. Computerized tomographic staging of renal trauma: 85

consecutive cases. J Urol. 1986;136:561–565.

48. McGonigal MD, Lucas CE, Ledgerwood AM. The effects of treatment of renal trauma on renal function. J Trauma.

1987;27:471–476.

49. Carroll PR, Klosterman PW, McAninch JW. Surgical management of renal trauma: Analysis of risk factors,

technique, and outcome. J Trauma. 1988;28:1071–1077.

50. Olsen WR. The serum amylase in blunt abdominal trauma. J Trauma. 1973;13:200–204.

51. Wynn M, Hill DM, Miller DR, Waxman K, Elsner ME, Gazzaniga AB. Management of pancreatic and duodenal

trauma. Am J Surg. 1985;150:327–332.

52. Cogbill TH, Moore EE, Feliciano DV, et al. Conservative management of duodenal trauma: A multicenter

perspective. J Trauma. 1990;30:1469–1475.

53. Drasar BS, Shiner M, McLeod GM. Studies on the intestinal flora. Gastroenterology. 1969;56:71–79.

54. Rivkind AI, Siegel JH, Dunham CM. Patterns of organ injury in blunt hepatic trauma and their significance for

management and outcome. J Trauma. 1989;29:1398–1415.

55. Saifi J, Fortune JB, Graca L, Shah DM. Benefits of intra-abdominal pack placement for the management of

nonmechanical bleeding. Arch Surg. 1990;125:119–122.
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56. Beal SL, Ward RE. Successful atrial caval shunting in the management of retrohepatic venous injuries. Am J Surg.

1989;158:409–413.

57. Cogbill TH, Moore EE, Jurkovich GJ, Feliciano DV, Morris JA, Mucha P. Severe hepatic trauma: A multi-center

experience with 1,335 liver injuries. J Trauma. 1988;28:1433–1438.

58. Lucas CE. Splenic trauma. Ann Surg. 1991;213:98–112.

59. Pickhardt B, Moore EE, Moore FA, McCroskey BL, Moore GE. Operative splenic salvage in adults: A decade

perspective. J Trauma. 1989;29:1386–1391.

60. Cogbill TH, Moore EE, Jurkovich GJ, Morris JA, Mucha P, Shackford SR. Nonoperative management of blunt

splenic trauma: A multicenter experience. J Trauma. 1989;29:1312–1317.

61. Feliciano DV, Cruse PA, Mattox KL, et al. Delayed diagnosis of injuries to the diaphragm after penetrating

wounds. J Trauma. 1988;28:1135–1144.

62. Maddox PR, Mansel RE, Butchart EG. Traumatic rupture of the diaphragm: A difficult diagnosis. Injury.

1991;22:299–302.

63. Kaulesar-Sukul DMKS, Kats E, Johannes EJ. Sixty-three cases of traumatic injury of the diaphragm. Injury.

1991;22:303–306.

64. Ivatury RR, Simon RJ, Weksler B, Bayard V, Stahl WM. Laparoscopy in the evaluation of the intrathoracic

abdomen after penetrating injury. J Trauma. 1992;33:101–109.

65. Burch JM, Ortiz VB, Richardson RJ, Martin RR, Mattox KL, Jordan GL Jr. Abbreviated laparotomy and planned

reoperation for critically injured patients. Ann Surg. 1992;215:476–484.

66. Morris JA Jr, Eddy VA, Blinman TA, Rutherford EJ, Sharp KW. The staged celiotomy for trauma: Issues in

packing and reconstruction. Ann Surg. 1993;217:576–586.

67. Carrillo C, Fogler RJ, Shaftan GW. Delayed gastrointestinal reconstruction following massive abdominal

trauma. J Trauma. 1993;34:233–235.
Extremity Injuries

499

RAYMOND R. LUPKAS, JR., M.D.*; AND RONALD F. BELLAMY, M.D.†

Chapter 21

EXTREMITY INJURIES

INTRODUCTION

INJURY PATTERNS

THE NATURE OF EXTREMITY INJURIES SEEN IN COMBAT CASUALTIES

Management

Surgical Treatment

Immobilization

COMPLICATIONS

Compartment Syndrome

Thrombolic and Embolic Phenomena

ANESTHETIC MANAGEMENT OF COMBAT CASUALTIES

Regional Anesthesia

General Anesthesia

INTRAOPERATIVE MONITORING

SUMMARY

*Formerly, Major, Medical Corps, U.S. Army; Anesthesia and Operative Service, Walter Reed Army Medical Center, Washington, D. C. 20307-

5001; currently, Staff Anesthesiologist, Moore Regional Hospital, Page Road, Pinehurst, North Carolina 28374

†Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

500

INTRODUCTION

Combat casualties with orthopedic and soft-tissue injuries of the extremities constitute the majority of soldiers who require operative procedures in

the corps and communications zones.1 These injuries are usually not life threatening but are the

major source of man-days lost by combat casualties.

Extremity injuries are usually found in the secondary survey of the American College of Surgeons’

Advanced Trauma Life Support (ATLS) examination unless the casualty has an obvious external

hemorrhage associated with the injury.2 In corps

zone hospitals, casualties with extremity injuries

undergo resuscitative surgery that is designed to

control hemorrhage, decontaminate wounds, and

stabilize fractures so the casualty can safely and

comfortably be evacuated to hospitals in the communication zone or the continental United States

(CONUS). Corrective surgery is undertaken in

the higher-echelon hospitals for the purpose of

closing wounds and restoring function. Providing anesthetic care in the corps support zone to

casualties with extremity wounds may be difficult because such injuries commonly coexist with

much more life-threatening injuries to the head

or trunk. Multiple or simultaneous procedures

that involve multiple surgical teams attending

the casualty together or in succession may be

required.

INJURY PATTERNS

The nature and severity of extremity injuries

depend on the mechanism of injury. In general, the

magnitude of injury depends on the magnitude of

energy transferred to the tissue. High-energy blunt

trauma (eg, a high-speed motor vehicle accident) is

associated with extensive soft-tissue destruction

and severely comminuted fractures.3 These generally need to be reduced early to control bleeding

and infection; early treatment also allows early

mobilization to enhance pulmonary toilet. Frequently there are coexisting injuries to the cardiac,

pulmonary, abdominal, and renal organ systems

that complicate the injury. Fat emboli, thromboemboli, deep venous thrombosis, and adult respiratory distress syndrome often complicate the longterm care of the casualty.3,4

Low-energy blunt trauma (eg, skiing injuries and

some falls) cause relatively simple fractures with

minimal soft-tissue destruction. These usually require less-complex treatment and are not usually

associated with severe coexisting injuries.

As with injuries caused by blunt trauma, the

nature of penetrating injuries depends on the

amount of kinetic energy transferred to the tissues.

However, because the rate of energy transfer is

much greater with penetrating injuries from, say, a

bullet than it is with blunt trauma from, say, a

vehicular bump, the same amount of energy transferred by the former mechanism will cause more

damage.

With penetrating injuries, the kinetic energy is

related to the mass of an object multiplied by its

velocity squared. Therefore, doubling the velocity

increases the kinetic energy 4-fold. The kinetic

energy determines the maximum amount of energy

that can be transferred, but whether the energy

transfer actually occurs is determined by other factors, of which shape, stability, and construction of

the missile are especially important. The small M16

bullet—even though its muzzle velocity is high—

possesses less than half the kinetic energy of typical

rifle bullets used during World War II; yet the M16

bullet is notorious for causing severe damage. Because of its propensity to fragment, a much greater

fraction of the kinetic energy of the M16 bullet is

usually transferred to the target tissue than occurred with bullets fired by earlier rifles. The surrounding tissue is damaged extensively by both the

fragments and the temporary cavitation that is

caused by the massive energy transfer. Skeletal

muscle will be injured (a) by direct cutting and

laceration caused by the bullet or fragments and (b)

by being ripped apart by the stretch of cavitation.

Several millimeters of necrotic muscle characteristically line the wound tract, although the major

threat arises from infection in the surrounding

tissue because it is both contused and contaminated with foreign material brought into the

wound.5

In contrast, a low-velocity, penetrating injury

(eg, a knife wound) is associated with only the local

injury directly imposed by the object itself. A shotgun blast from a distance imparts only comparatively little energy to the body; when the wound is

made at point-blank distance, however, all of the

shell’s energy—which is equal to that of an assault

rifle bullet and is therefore much more dangerous—

is imparted.
Extremity Injuries

501

THE NATURE OF EXTREMITY INJURIES SEEN IN COMBAT CASUALTIES

one third of extremity operations will be to treat

injuries that involve only soft tissue (ie, skin, fat,

and skeletal muscle). The remaining two thirds of

extremity operations will be for injuries that involve soft tissue in addition to injuries to deeper

structures such as long bones and neurovascular

structures.6 It is these latter injuries that may especially challenge the military anesthesiologist.

The prevalence of purely soft-tissue injuries has

increased in recent wars due to the more frequent

use of improved fragmentation munitions. These

characteristically cause multiple, small fragment

wounds (Figure 21-1). Another form of purely softThe database compiled during the Vietnam War

by the Wound Data and Munitions Effectiveness

Team (WDMET) is a unique, underutilized repository of first-hand information on war wounds and

the mechanisms of injury. (Chapter 1, Combat Trauma

Overview, discusses WDMET data in some detail.)

Analysis of the WDMET data reveals that about one

half of combat casualties who survive long enough

to be evacuated to the hospital level have injuries that

involve only the extremities. In addition, a sizable

number of the remaining casualties have injuries of

the extremities in addition to more-serious injuries

of the head or trunk (ie, combined injuries). About

Fig. 21-2. (a) This casualty’s through-and-through wound in the posterior thigh was made by a bullet fired by a .38-

caliber pistol at close range. (b) The wound has been incised and the subcutaneous tissue superficial to the muscle

fascia has been excised. It is possible that this wound could have been treated nonsurgically. Photographs: Swan

Vietnam Surgical Slide Collection.

b

Fig. 21-1. (a) This casualty has multiple, tiny, fragment wounds of his lower extremities that were caused by handgrenade fragments. (b) The surgeons have elected to excise some of the larger wounds, although there was probably

little tissue damage or contamination. Photographs: Swan Vietnam Surgical Slide Collection.

a b

a
Anesthesia and Perioperative Care of the Combat Casualty

502

Fig. 21-3. This soldier was struck by several fragments from an

exploding booby trap. (a) Wounds of entrance are seen in the left

lateral thigh and just proximal to the right knee. There were no

wounds of exit. (b) The radiograph shows a grossly comminuted

fracture of the middle portion of the left femur. Several metallic

foreign bodies are seen. (c) The radiograph shows intact bones in

the casualty’s right knee. Several small metallic foreign bodies are

seen. (d) The casualty’s appearance after wound debridement. The

extensive nature of the operation carried out on the left thigh is

justified by the need to excise injured soft tissue in proximity to the

femur fracture. The extensive nature of the operation carried out

on the casualty’s right thigh is justified by the need to preclude an

injury to the superficial femoral artery. (e) The casualty had delayed primary closure on the 6th day after the injury. Photographs:

Swan Vietnam Surgical Slide Collection.

d

c

e

b

a
Extremity Injuries

503

tissue injury is the en seton (ie, through-and-through)

gunshot wound (Figure 21-2). Although en seton

wounds may be made by high-velocity bullets, the

tissue damage is surprisingly small because energy

transfer has been minimized by the failure of the

bullet to yaw, tumble, fragment, or deform. The

treatment of an en seton wound should be no different from the treatment given to a casualty with a

wound made by a low-velocity bullet fired from a

civilian hand gun.

By way of contrast, very extensive soft-tissue

wounds are frequently seen in conjunction with

open, comminuted, long-bone fractures (Figures

21-3 and 21-4). In these wounds, the missile is

stopped by the bone with consequent maximal energy transfer, which, together with secondary missiles arising from bone fragments, causes massive

tissue damage.

Even more massive tissue damage to the extremities is found in casualties who detonate antipersonnel mines or who are injured by shaped-charge

warheads. Such injuries almost always result in

traumatic amputations (Figure 21-5).

The increasing likelihood of involvement by the

U.S. military in operations other than war (OOTW)

makes it likely that military anesthesiologists will

b

c

Fig. 21-4. (a) This soldier was wounded in the lower

extremities by the detonation of an explosive munition. (b) A severely comminuted fracture of the

casualty’s right ankle. (c) The operative exposure of

the fracture site. Photographs: Swan Vietnam Surgical

Slide Collection.

be confronted by casualties, many of whom are

civilians, who have neglected extremity injuries.

Figure 21-6 shows such a patient.

In the WDMET database, about 35% of the

extremity injuries involve an isolated fracture of

an extremity long bone. Lower-extremity fractures

were 2.5-fold more common than those of the upper extremity. About 12% of casualties with extremity wounds had fractures of the bones of the

hands or feet. About 7% of casualties with extremity wounds had a major extremity amputation (arm

or leg) and about 5% had amputations of the hands,

feet, fingers, or toes. Of casualties with extremity

wounds, 12% had an isolated vascular injury (the

femoral artery the most common), and 5% had an

isolated nerve injury (the sciatic nerve the most

common).

Of casualties who survived to reach the hospital

level, 6% had an injury that involved both a fractured bone and a vascular or nerve injury. The most

common combinations were a fractured femur and

a femoral arterial injury, and a fractured humerus

with an injury to the radial nerve.

In summary, the most common extremity injuries—exclusive of those of soft tissue only—likely to

be seen by the military anesthesiologist are

a
Anesthesia and Perioperative Care of the Combat Casualty

504

b

d

Fig. 21-5. (a) This soldier detonated an antipersonnel mine; a traumatic amputation of the distal portion of his

foot (ie, the forefoot) has occurred. (b) The radiograph shows the extent of bony injury. (c) A formal forefoot

amputation is in progress. (d) The finished amputation. Note that the forefoot has been removed at the talus. This

is known as a Syme’s amputation. Retaining sufficient skin to cover the stump is sometimes difficult to achieve

with this procedure. Photographs: Swan Vietnam Surgical Slide Collection.

• an open, comminuted fracture of a long

bone, the femoral shaft being the most common site;

• an amputation of the leg, arm, hand, or

foot; and

• an isolated vascular injury, the superficial

femoral artery being the most common site.

Management

Shock and sepsis are the two most serious medical treatment problems that may arise in combat

casualties with extremity trauma. The relative importance of these two causes of death has been

changed by modern military surgery. During World

War I and earlier wars such as the American Civil

War, sepsis in the injured extremity was the most

frequent cause of death in hospitalized casualties. With the use of wound excision and antibiotics, life-threatening sepsis has become much

less common.

a

c

Shock

Extremity wounds can be fatal. The WDMET

database indicates that about 9% of casualties with

extremity wounds that involved more than just

soft-tissue damage died. Most casualties with injured extremities who were fatally wounded were

killed in action; the most common cause of death

was exsanguination—from amputation of an arm

or a leg, or from lacerations of the femoral artery.

The few casualties with extremity injuries who are

at risk of dying at the hospital level have sustained

either massive blood loss or have developed lifethreatening sepsis, usually from an anaerobic wound

infection.

Blunt injuries to the extremities may also be associated with hypovolemic shock secondary to hemorrhage, but this occurrence is due not to massive

hemorrhage but to prolonged, slow bleeding secondary to rupture of intraosseous blood vessels or

lacerations of blood vessels near the site of frac-
Extremity Injuries

505

d

b

Fig. 21-6. (a) This woman has a 3-day-old open comminuted fracture of the left femur that was caused by a perforating

gunshot wound. (b) The radiograph shows the comminuted fracture. (c) A close-up view of the wound of entrance. The

wound shows signs of anaerobic sepsis. (d) An above-the-knee amputation of the guillotine type has been performed.

Such an operation may be lifesaving when the patient has an infected open fracture. Photographs: Swan Vietnam

Surgical Slide Collection.

c

a

TABLE 21-1

POTENTIAL BLOOD LOSS FROM CLOSED

FRACTURES

Expected

Blood Loss

(mL) Bone Fractured

500 Forearm: radius and/or ulna

750 Elbow

Tibia

Ankle

1,000 Humerus

Femoral shaft

1,250 Hip

> 1,500 Pelvis

Adapted with permission from Shumaik GM. Extremity

trauma. In: Baxt WG, ed. Trauma: The First Hour. Norwalk, Conn:

Appleton-Century-Crofts; 1985: 227.

ture.4,7 Large volumes of blood can be sequestered

in limbs even without significantly changing limb

size.8 Therefore, refractory shock in the casualty

with blunt trauma to an extremity requires that a

search be made for occult fractures. Large volumes of blood and blood products may be required, and coagulopathies should be anticipated

(Table 21-1).

Pneumatic antishock garments can be beneficial

in stabilizing fractures. These trousers have limited

value in correcting hypovolemia, as the intravascular volume returned to the central circulation is

minimal. They are beneficial in that they temporarily stabilize fractures of the pelvis and lower

extremity and decrease the bleeding.9

Sepsis

The goal of military medical management is to

return the injured soldier to full duty. This is

accomplished by promoting rapid and complete
Anesthesia and Perioperative Care of the Combat Casualty

506

healing of the wound. Sometimes, as in the case of

an amputation, this is not possible. Return to duty

is also unlikely for many casualties with severe

fractures or nerve injuries. In most casualties, the

major factor delaying wound healing and return to

duty is sepsis, which occurs in about 5% of casualties with pure soft-tissue injuries but in as many as

30% or more of casualties with open, comminuted

fractures of the femoral shaft.10,11

Wound sepsis is prevented by surgical excision

of the contaminated and damaged tissue lining the

wound tract. The operation is commonly known as

debridement, although, strictly speaking, debridement means only wound incision. In general, the

amount of tissue to be excised is related to the size

of the wound. Tiny extremity wounds can be left

alone, but this is rarely the case with the large

wounds of exit that frequently accompany extremity fractures. Even in casualties with only softtissue wounds, debridement can be an extensive

operation (see Figure 21-1). Perioperative administration of antibiotics—especially if they suppress

the growth of clostridial bacteria and Streptococcus

pyogenes—may be a useful adjunct. Wound sepsis

that occurs weeks after injury is usually the result of

the growth of staphylococci or Gram-negative organisms in open wounds that contain dead tissue.

Such wounds require redebridement.

Surgical Treatment

The most common operative procedure performed by military surgeons is wound debridement,

and the most common sites for this operation are

the extremities. The goal of debridement is to

decontaminate injured tissue so that healing is not

impeded by local infection. Following debridement, a surgical intervention is usually required to

bring about wound closure. In contrast to civilian

practice, the military surgeon rarely closes the

wound at the time of initial debridement. The most

common approach, with the patient anesthetized, is

to inspect the wound 4 to 6 days after wounding and

to close the wound at that time if there is (a) no

evidence of other than superficial infection and (b)

little necrotic tissue that cannot be easily removed.

This procedure is known as delayed primary closure.

The delay in closure is a consequence of both the

inability of the surgeon to be certain that all damaged and contaminated tissue has been removed

and the provision of military medical care by echelons. Primary closure by a surgeon at one echelon,

followed by the patient’s evacuation to a higher

echelon, would remove the casualty from observation just when the most lethal form of sepsis—gas

gangrene—is most likely to appear.

Secondary closure is the name applied to the operation performed on extremity wounds that cannot undergo delayed primary closure but are closed

after the appearance of granulation tissue—7 to 10

days after wounding. Some amputation stumps

undergo secondary closure; however, most are not

closed surgically but are allowed to close by scaring, a process known as healing by secondary intention. Reamputation of the stump is a common

operation: the soft tissue retracts so much that the

bone is relatively too long.

The most common vascular injuries involve the

femoral artery, brachial artery, and femoral vein.

Arterial reconstruction usually necessitates the insertion of a vein segment, which is usually taken

from the saphenous vein of the opposite leg.

Reoperation is a common occurrence following extremity arterial reconstructions in combat casualties: thrombosis, delayed hemorrhage, and wound

sepsis seem to be more common than in civilian

patients who have peripheral vascular operation. If

the vascular injury coexists with a fracture, it is

essential that the fracture first be stabilized. External fixation is especially useful for this purpose. It

is desirable to reconstruct an injured femoral vein,

especially when there is a coexisting injury to the

femoral artery. In most venous reconstructions,

thrombosis probably occurs in the repaired vein

within 2 to 3 days; however, the vein stays open

long enough to keep the arterial reconstruction

open during the critical first 2 or 3 days. Venous

ligations may be an acceptable alternative to reconstruction in the casualty with multiple injuries.

Immobilization

Because fractures are very common in soldiers

with extremity wounds, immobilization is a necessary part of most extremity operations. In general,

three approaches to fracture immobilization can be

employed in preparing the casualty for evacuation

from the combat or communication zones:

1. Internal fixation, wherein a metal rod is

inserted longitudinally through the marrow cavity, or metal screws and plates are

used to hold the fracture together. This

approach is rarely desirable in combat casualties with open, comminuted fractures

because of the strong possibility of sepsis.

2. External fixation, wherein long, threaded

rods are inserted transversely into the bone
Extremity Injuries

507

fragments above and below the fracture

site and are held in place externally by an

adjustable frame. This is an increasingly

favored means of immobilizing fractures

such as those of the tibia, but the approach

depends on the availability of the necessary equipment.

3. Plaster of paris cast or splint, which is the

traditional approach to immobilizing fractures, and is still the best approach to high

femoral-shaft and hip fractures. The drawbacks to this approach are the discomfort

of the casualty and the difficulty of exposing the soft-tissue component of the wound.

COMPLICATIONS

Injuries to other parts of the body frequently

coexist with extremity injuries. The most common

combinations are abdomen and legs, especially when

the wounds are made by buried explosive munitions; and head, upper torso, and arms, when the

wounds result from the detonation of a shapedcharge warhead. Wounds to the abdomen are discussed in Chapter 20, Abdominal Injuries; to the

head in Chapter 16, Neurological Injuries; and to

the upper torso in Chapter 19, Thoracic Injuries.

In addition to managing combined injuries, the

military anesthesiologist needs to be prepared to

manage complications that are unique to extremity

injuries, of which compartment syndrome and

thrombolic and embolic phenomena are the most

serious.

Compartment Syndrome

Although compartment syndromes are not common in combat casualties for the simple reason that

the wound tract usually decompresses the compartment via the wounds of entrance or exit, it may be

seen following vascular reconstructions, especially

when there has been a delay in operating.12 Compartment syndromes are orthopedic emergencies

that require early treatment to prevent long-term

disability.4,13 The myofascial compartments are of a

fixed volume, and after injury, edema and hemorrhage cause increased pressure in this fixed space.

The increased pressure causes decreased venous

outflow and decreased microvascular perfusion of

the tissues. As muscle dies, it losses its normal

ability to regulate intracellular water and electrolyte concentrations. The result is a vicious cycle:

swelling of the cells, further increase in compartment pressure, and decreased arterial flow.3,14 If the

cycle is not interrupted by early fasciotomy to decrease tissue pressure, severe muscle necrosis and

peripheral nerve damage will follow, and a severely disabled, fibrotic myofascial compartment

with severe disability will be the result (Figure 21-7).

Pain is the most frequent symptom of increased

compartment pressures.3 Decreased pulses distal

to a fracture site should be a warning of an impending compartment syndrome or vascular injury.

While full evaluations of motor and sensory function are difficult to perform early in the management of an extremity injury, function distal to a

fracture site suggests that peripheral nerve damage, if any, is incomplete. Early diagnosis is important to decrease damage to the tissue. The clinical

picture can be confusing, but pain on passive range

of motion of the affected muscle and distal sensory

deficits are the most reliable indicators. The patient

will complain of subjective pain out of proportion

to the degree of apparent injury, and may note a

tense feeling in the tissue. Physical examination can

reveal tense compartments with warm, tense skin

overlying the area. Pain with passive range of

motion of the joint is an important indicator, but can

be confusing in the presence of other injuries.15

Laboratory determinations are of little help in combat zone hospitals because the needed tests are not

available, but elevated levels of creatine kinase and

myoglobinuria are consistent with muscle destruction.

Compartment pressures can be evaluated in fractured limbs or in nonfractured limbs where the

mechanism of injury suggests ischemia (ie, crush

injury).3 These pressure determinations can be helpful when the patient is unable to answer questions

(eg, the patient is under anesthesia, uncooperative,

or has proximal nerve injury and sensory nerve

damage). The most common method of determining compartment pressure is to insert an 18-gauge

needle into the compartment in question, and then

connect the needle to a pressure transducer. There

are no absolute pressure ranges to allow a definitive

diagnosis. The normal intramuscular pressure is 0

to 8 mm Hg.16 Various investigators recommend

fasciotomy at various pressures: from 30 to 35 mm

Hg,17 to greater than 45 mm Hg,18 to decompression

when the intramuscular pressure is within 10 to

30 mm Hg of the diastolic pressure.19

Although the preceding discussion has emphasized the deleterious local effects of compression

syndrome, dire systemic effects may also occur.
Anesthesia and Perioperative Care of the Combat Casualty

508

cardiopulmonary disease, those who have multiple

injuries have multiple risk factors to develop a

hypercoagulable state. Trauma to femoral or pelvic

veins is associated with a high incidence of deep

venous thrombosis and subsequent pulmonary

embolism.20,21 Additionally, surgery, venous stasis,

trauma, immobilization, vascular damage, disseminated intravascular coagulation, thrombocytopenia,

and the administration of heparin are associated

with deep venous thrombosis.22,23 Peripheral thrombosis below the knee is common in surgical patients, with an incidence approaching 45%, and

with 10% of these patients having symptoms of

pulmonary embolism.24 Casualties having major

lower-limb orthopedic reconstruction are at high

risk for two reasons: (1) there is extensive vascular

damage and (2) they will be immobilized for an

extended time. It seems unlikely that combat casualties who have had extremity venous reconstructions are at a higher risk of deep venous thrombosis

and pulmonary embolism than are casualties with

isolated arterial reconstructions and casualties in

whom the venous injury has been treated by ligation. Patients with thrombophlebitis and patients

older than 40 years of age with extensive abdominal

When systemic effects are present, the condition is

known as crush syndrome. When the ischemic

region is reperfused—either when arterial inflow

is restored following a vascular reconstruction or

when external compression is relieved, untreated

or inadequately treated—the injured area may swell

explosively due to fluid sequestered there. In addition, myoglobin from necrotic muscle is washed

into the systemic circulation, which, in conjunction

with hypovolemia, can cause acute renal failure.

The prudent military anesthesiologist will see that

a prophylactic approach is taken to prevent compartment syndrome by assuring that fasciotomies

are performed in all casualties with extremity

wounds whose arterial reconstruction has been delayed.

Thrombolic and Embolic Phenomena

Deep Venous Thrombosis and Pulmonary

Embolism

The multiply injured combat casualty is at risk

for deep venous thrombosis and pulmonary embolism. While soldiers usually have no underlying

Compartment Syndrome

Restoration of Blood Flow

Into Ischemic Extremity

Compartmental Hypertension

Decreased Perfusion Edema

Compartmental Tamponade

Muscle Ischemia Neural Ischemia

Crush Syndrome

Muscle Necrosis Volkmann’s Contracture

Acidosis

Third-Space Fluid Loss Myoglobinuria Hyperkalemia

Shock Acute Renal Failure Cardiac Arrhythmias

Fig. 21-7. The pathophysiology of compartment and crush syndromes. Adapted with permission from Kitka MJ, Meyer

JP, Bishara RA, Goodson SF, Schuler JJ, Flanigan P. Crush syndrome due to limb compression. Arch Surg. 1987;122:1078–

1081.
Extremity Injuries

509

surgery have an incidence of calf-vein thrombosis

of 40% to 80%, proximal vein thrombosis of 10% to

20%, and fatal pulmonary embolism of 1% to 5%.25

Clearly, pulmonary embolism is a major risk factor

in this surgical group, and recognition, treatment,

and prophylaxis are mandatory.

Intraoperative presentations are quite dramatic

and have been associated with leg manipulation,

wrapping the leg with Esmarch bandage, and

realigning of the proximal femoral fracture component; they have been seen days after the initial

trauma.26,27 The hemodynamic picture is one with

increased central venous and pulmonary artery pressures, hypotension, and tachycardia.28 The pulmonary capillary wedge pressure is unchanged unless

there is underlying cardiac disease.29 The cardiac

output does not correlate to the degree of obstruction of the pulmonary vasculature.28 The right

ventricle is prone to failure, as it is a highly compliant ventricle that decompensates with acute increases in right ventricular afterload.30–32 The degree of pulmonary hypertension correlates with the

acute degree of obstruction. The mean pulmonary

artery pressure never exceeds 40 mm Hg unless

there is coexisting cardiac disease. A pulmonary

artery pressure of 22 mm Hg correlates with a 30%

obstruction of pulmonary vasculature, while 36 mm

Hg correlates with 50% obstruction.28 Further decompensation occurs when a coexisting patent foramen

ovale allows right-to-left shunting of blood when

pressure on the right side of the heart exceeds

pressure on the left.33

Bilateral wheezing and arterial blood gas evidence of hypoxemia and hypercarbia, together

with nonspecific roentgenographic chest findings,

should alert the prudent practitioner to the possibility of pulmonary embolism.34,35 As dead-space

ventilation increases secondary to decreased perfusion, atelectasis ensues, with loss of surfactant in

the involved alveoli. Platelet-mediated vasoconstriction and bronchospasm also contribute to the

clinical picture.

Diagnosis. The diagnosis of pulmonary embolism needs to be made early because empirical treatment with heparin can lessen the disease process.34

Pulmonary angiography is the standard for diagnosis but is very invasive and may be difficult to

perform in combat zone hospitals. Ventilation–

perfusion scans attempt to demonstrate lack of perfusion to ventilated lung; however, these are associated with a 25% to 40% false-negative rate in lowprobability scans, and a 29% false-positive rate in

high-probability scans. As most emboli arise in the

proximal veins, impedance plethysmography is a

highly specific, noninvasive test that can diminish

the need for angiograms.36 When needed, a pulmonary artery catheter can be used for pulmonary

arteriography.

Treatment. The aim of treatment is to maximize

the cardiac output and oxygen delivery to the body

tissues. In the early treatment of the patient with

right ventricular failure secondary to pulmonary

embolism, the arterial partial pressure of oxygen

decreases due to increased shunting of blood in the

pulmonary bed. But oxygen delivery may actually

be increased to tissues, since the mixed venous

oxygen content is increased.37

Judicious volume infusion is indicated to increase

central venous pressure to 12 to 15 mm Hg. Increasing the central venous pressure can shift the interventricular septum and compromise left ventricular filling because the noncompliant pericardium

produces tamponade-like hemodynamics.38

Inotropic drugs are used to improve both the

cardiac output and coronary perfusion. When the

right ventricle is failing, there is a decrease in right

ventricular perfusion and a loss of the continuous

perfusion that is seen on the right side of the normal

heart. This leads to a vicious cycle: decreased cardiac output leads to decreased perfusion, which

leads to further decreased cardiac output, which

leads to further decreased perfusion, and so on.

Isoproterenol has been tried, but hypotension,

tachycardia, and dysrhythmias have detracted from

its usefulness.39 After volume loading to central

venous pressure of 12 to 15 mm Hg, dobutamine40

and dopamine39 have been used successfully to increase cardiac output, maintain blood pressure, and

decrease pulmonary vascular resistance. In dog

models, norepinephrine has increased cardiac output with improvement of right ventricle perfusion.41

Pulmonary vasodilators such as prostaglandin

E1 are nonspecific systemic vasodilators and can

decrease right ventricular perfusion, and have been

combined with norepinephrine.34

Heparin has been shown to reverse pulmonary

vasoconstriction and bronchoconstriction from

thrombin activation and platelet aggregation. Administering a bolus of heparin has been recommended when the clinical picture is highly suggestive of pulmonary embolus (even before definitive

diagnosis).33,42–45 The possibility of increasing a

surgical patient’s risk of hemorrhage must be

weighed against heparin’s vasodilating and

bronchodilating actions.

Positive end-expiratory pressure (PEEP) needs to be

used judiciously, if at all. Venous return to the heart is

impeded, and stress to the right ventricular wall and
Anesthesia and Perioperative Care of the Combat Casualty

510

monary hypertension soon developed and culminated in the opening of a probe patent foramen

ovale, through which an ultimately fatal paradoxical embolization occurred.55 It seems reasonable to

speculate that fat emboli frequently occur when

long-bone fractures are manipulated.

Studies with dogs have demonstrated that when

the fat embolism syndrome is induced by fracturing

the femurs, the fat found in the lung parenchyma

has the same lipid profile as that seen in the bone

marrow.56 As there are only small quantities of

femoral fat, other mechanisms must be at work to

account for both the severe damage that is seen in

the lung parenchyma and the neurological dysfunction, as they cannot be explained by simple vascular

occlusion alone.54

Free fatty acids and platelet-mediated factors are

postulated to increase the damage to the lung parenchyma. Multiple studies have demonstrated

that free fatty acids damage lung tissue.57–59 Because free fatty acids are increased as part of the

stress response to injury, it is postulated that they

work synergistically with the fat emboli to induce

tissue damage (Figure 21-8).60 This concept is difficult to demonstrate in the laboratory because free

fatty acids caused by the trauma cannot be separated from those that are caused by local tissue

injury.

Platelet aggregation around the fat microemboli

can also cause lung damage. The platelets release a

variety of mediators to cause vasospasm and

oxygen consumption are increased. Small tidal volumes at rapid rates with no PEEP will help maximize

cardiac output and mixed venous oxygen.46–48

Prophylaxis. Along with maintaining a high

index of suspicion, military trauma anesthesiologists need to consider prophylaxis against deep

venous thrombosis in all patients with orthopedic

injuries. Low-dose heparin (5,000 units administered subcutaneously 2 h before surgery and every

8 h after, for several days) has been shown to decrease deep venous thrombosis, but it increases

intraoperative bleeding, and there is no overall

decrease in mortality.49 Another concern with administering heparin is bleeding when regional anesthesia is used. External pneumatic compression

stockings decrease venous stasis, induce fibrinolysis, are as effective as low-dose heparin,50,51 and are

especially effective when heparin is contraindicated.

There may be decreased thrombosis when regional

anesthesia has been used in hip and prostate surgery. The most effective prophylaxis is patient

ambulation.

Fat Embolism Syndrome

Death as a result of fat embolism syndrome was

first recognized in 1862. The syndrome has usually

been diagnosed when there are fat globules demonstrated in the blood with predisposing conditions

such as long-bone fracture. The classic triad (neurological dysfunction, respiratory insufficiency, and

petechial skin rash) is only seen in 1% to 5% of

patients with fat emboli. In contrast, respiratory

insufficiency is seen in as many of 29% of patients

with fat emboli, as demonstrated by arterial bloodgas monitoring.52

Pathophysiology. The pathophysiology of fat

embolism syndrome is complex and not fully elucidated. The consensus is that fat globules gain access to the venous circulation through torn venules.53

Long-bone fractures are commonly the source of fat

emboli, but the syndrome is also seen with joint

replacements, liposuction, bone marrow transplants,

acute hemorrhagic pancreatitis, carbon tetrachloride poisoning, and external cardiac massage.54

An especially dramatic presentation of the fat

embolism syndrome was reported in 1994, occurring in a patient who was undergoing intramedullary fixation of a femoral-shaft fracture. A twodimensional transesophageal Doppler probe had

been inserted as part of the patient’s monitoring.

Every time the femur was manipulated, a swarm of

emboli appeared in the right side of the heart. PulMarrow Fat Emboli

Microvascular Occlusion

Platelet Lysis Triglyceride Breakdown

by Tissue Lipases

5-Hydroxytryptamine Free Fatty Acids

(Serotonin) Release

Tissue Damage

Fig. 21-8. Pathophysiology of the fat embolism syndrome.

Reprinted with permission from Van Besouw J-P, Hinds

CJ. Fat embolism syndrome. Br J Hosp Med. 1989:42:304.
Extremity Injuries

511

EXHIBIT 21-1

DIAGNOSTIC FEATURES OF FAT EMBOLISM SYNDROME

Major Features

Respiratory insufficiency occurs 2 to 3 days after the injury in 75% of patients with fat emboli syndrome.1

Tachypnea, dyspnea, and fine inspiratory rales are the usual clinical manifestations. Initial chest radiography is usually normal. As the disease progresses, bilateral, fluffy shadows and obliteration of the lung fields

develop (appearing like adult respiratory distress syndrome). Respiratory failure occurs in 10% of cases.2

Hypoxemia generally precedes respiratory distress by several hours and is considered to be a sensitive

marker for the initiation of therapy.3

Central nervous system signs and symptoms can be early, often preceding respiratory symptoms by 6 to 12

hours and can be the primary cause of death.4 Patients usually develop an encephalopathy manifested by

a confused state that is exacerbated by hypoxia and not resolved by supplemental oxygen. Associated focal

neurologic signs include hemiplegia, aphasia, apraxia, scotoma, and anisocoria.3,5 These focal symptoms are

secondary to the local effects of vascular occlusion. These are seen as widespread destruction in the white

matter of the cortex, brainstem, and spinal cord and are secondary to platelet aggregation and free fatty acid

mechanisms of injury.

Dermatological manifestations are seen as a petechial rash in the oral mucous membranes, conjunctiva, and

skin folds of the upper half of the body (especially the neck and axilla). This rash, which is seen in 60% of

those affected, is secondary to the occlusion by fat globules of the dermal capillary network.1,6 The petechiae

are seen on the nondependent body aspects, and are probably secondary to the embolization within the

nondependent portions of the subclavian and carotid artery (analogous to oil floating on water). The rash

is self-limited and resolves completely in 7 to 10 days.7,8

Minor Features

Pyrexia and tachycardia, which are related to the fat embolism itself or to secondary infection9,10

Electrocardiographic changes, which are associated with right ventricular strain (S wave in V1, Q wave in III,

and nonspecific ST segment changes)

Retinal changes, which are manifested by soft, fluffy exudates; macular edema; retinal hemorrhages; and fat

droplets

Renal changes of oliguria, lipuria, proteinuria, and hematuria, which are transient with the fat embolus

syndrome and are unrelated to subsequent renal failure4

Hepatic changes, which are manifested by rare, self-limited jaundice1

(1) Gurd AR, Wilson RI. The fat embolism syndrome. J Bone and Joint Surg. 1974;56(B):408–416. (2) Guenter CA, Braun TE. Fat

embolism syndrome: Changing prognosis. Chest. 1981;79:143–145. (3) Gosling HR, Donohue TA. The fat embolism syndrome.

JAMA. 1979;241:2740–2742. (4) Sevitt S. The significance and pathology of fat embolism. Ann Clin Res. 1977;9:173–180. (5)

Jacobson DM, Terrence CF, Reinmuth OM. The neurologic manifestations of fat embolism. Neurology. 1986;36:847–851. (6)

Alho A. Fat embolism syndrome, etiology, pathogenesis and treatment. Acta Chir Scand. 1980;49:75–85. (7) Tachakra SS.

Distribution of skin petechiae in fat embolism rash. Lancet. 1976;1:284–285. (8) Stephens JH, Fred HL. Petechiae associated with

systemic fat embolism. Arch Dermatol. 1962;86:515–517. (9) Murray DG, Racz GB. Fat embolism syndrome (respiratory

insufficiency syndrome). A rationale for treatment. J Bone and Joint Surg. 1974;56(A):1338–1349. (10) Wildsmith JAW, Masson

AHB. Severe fat embolism: A review of 24 cases. Scott Med J. 1978;23:141–148.

bronchospasm with subsequent ventilation–perfusion mismatching.61 Hypoperfusion causes secondary cellular disruption, which then causes the release of secondary tissue lipases. This then causes

further increases in free fatty acids and further lung

injury.54

Fat emboli that bypass the filtering capacity of

the lung and gain access to the arterial circulation

(ie, right-to-left shunt) are responsible for the dermatological and neurological manifestations of the

syndrome. Normal shunting occurs through the

bronchial and thebesian veins and allows small

emboli to bypass the lung to the arterial circulation.

As the amount of emboli increases and damage is

occurring, the pulmonary artery pressure increases,

and the opening of precapillary shunts increases
Anesthesia and Perioperative Care of the Combat Casualty

512

the right-to-left shunt. This is associated with larger

emboli and more-severe systemic manifestations.62

Diagnosis. Fat embolism syndrome is difficult to

diagnose,63–65 although respiratory insufficiency,

central nervous system dysfunction, and dermatological manifestations are major diagnostic features;

fever, tachycardia, and electrocardiographic, retinal, renal, and hepatic changes are minor, nonspecific diagnostic features not specific to the fat embolism syndrome per se (Exhibit 21-1). In 1987, four

criteria (sustained PaO2 < 60 mm Hg; PaCO2 > 55 or

pH <7.3; respiratory rate > 35; and increased work

of breathing manifested by dyspnea, use of accessory muscles, and tachycardia) in the presence of a

long-bone fracture were suggested as being diagnostic.66 These criteria probably lead to overdiagnosis, which illustrates the difficulties of studying

the syndrome, its pathophysiology, diagnosis, and

treatment.

Laboratory Changes. The following hematological and biochemical changes can usually be seen in

patients with fat embolism syndrome.

• Hematological changes:

° Hematocrit usually decreases even in the

face of adequate blood-loss replacement.

This is usually due to intrapulmonary

hemorrhage, lung parenchymal damage,

and to increased blood aggregation and

hemolysis.54

° Platelet count is decreased secondary to

the platelets’ adherence to fat emboli and

raw edges of bone. In addition, disseminated intravascular coagulation will consume platelets.54

° Erythrocyte sedimentation rate is increased.

° Coagulation times (prothrombin and

thrombin) are increased.

• Biochemical changes:

° Fat globules can be detected in blood,

urine, and sputum but are not diagnostic

in the absence of other clinical signs.64

° Free fatty acids, cortisol, glucagon, and

catechols increase as part of the stress

response.62

° Calcium is decreased secondary to binding to free fatty acids.67

Treatment. The fat embolism syndrome is difficult to diagnose because universal agreement on

diagnostic criteria is lacking. This lack, coupled

with the relatively low incidence of the syndrome,

creates difficulties in prospectively evaluating

 treatment.

Treatment is supportive in nature. Because movement of the fracture increases the incidence of fat

embolism syndrome, early immobilization is advocated.68 Early immobilization will also allow early

patient mobilization to increase pulmonary toilet,

and decrease blood loss and platelet consumption

by stopping the constant movement at the fracture

site. Internal fixation decreases the incidence of the

syndrome.69,70

Adequate fluid resuscitation and maintenance of

colloid oncotic pressure with blood or colloid fluids

help to absorb circulating free fatty acids. Studies

with animals in hypovolemic shock have demonstrated their increased susceptibility to fat embolism syndrome.71 Albumin is thought to bind free

fatty acids, but this needs further investigation as to

the appropriate levels of albumin required.72 The

patient should be given adequate analgesia to ablate the sympathetic responses that will cause increased free fatty acids and susceptibility to fat

embolism syndrome.54

Respiratory care is of paramount importance in

the treatment of fat embolism syndrome. Oxygen

requirements range from supplemental oxygen provided via nasal catheter to intubation and PEEP

required for frank respiratory failure. The pulse

oximeter allows for noninvasive determination of

saturation and permits continuous monitoring of

pulmonary function.52

Neurological function must be evaluated serially

to determine early deterioration of function. There

is no information at present as to the incidence of

increased intracerebral pressure, or if measures

usually employed to control intracranial hypertension alter patient outcome.54

As alcohol is known to inhibit lipase, it was

postulated, but never proven, that inhibiting lipase

will limit the lipolysis of neutral fat emboli and

decrease free fatty acid damage to the lung.73 A

resurgence of interest in alcohol has developed

since researchers noted a decreased incidence of fat

emboli in patients with femoral fractures and elevated blood alcohol levels.74 However, no biochemical relationship has been demonstrated among

blood alcohol levels, free fatty acid level, and fat

embolism syndrome.75

Heparin, a stimulator of lipase, has been used to

decrease the number of circulating fat globules,

thereby preventing them from reaching the lung.74,75

Heparin will also cause an increase in free fatty

acids, which can cause increased damage. As exThis
Extremity Injuries

513

pected, the data conflict.76,77 Before administering

heparin, the medical officer must weigh the concern

of causing further bleeding against the continued

circulation of fat.

Steroids, usually methylprednisolone, have been

employed both prophylactically and therapeutically and may have beneficial effects, but all

investigators in steroid studies note the need for

adequate resuscitation and oxygen before using

steroids.54 The proposed mechanisms of action include stabilizing membranes, limiting the rise

of free fatty acids, limiting complement, and inhibiting leukocyte aggregation. Steroids appear to

attenuate the syndrome, and hypoxia has been

shown to decrease after steroids were administered: in 1971, methylprednisolone in a first dose of

125 mg, then 80 mg every 6 hours for 3 days, was

advocated78; in 1983, the dose was increased to 7.5

mg/kg every 6 hours for 12 doses (90 mg/kg total)79; and in 1987, 30 mg/kg was administered in

one dose.52

Prognosis. The multiplicity of coexisting injuries

makes the overall prognosis for patients with fat

embolism syndrome difficult to assess; overall, the

mortality is 5% to 15%, owing to the other injuries.

As expected, if no mechanical ventilation is required to treat the patient, the mortality decreases.52

Overall, the respiratory manifestations are self-limited, and if the physician maintains oxygenation,

then the patient’s respiratory function will return to

normal.80

Neurological complications are responsible for

most of the long-term morbidity and mortality,

especially when focal deficits are present.64,81

ANESTHETIC MANAGEMENT OF COMBAT CASUALTIES

The anesthetic management of combat casualties

with severe extremity wounds is demanding. The

more common injuries, such as grossly comminuted

femoral or tibial fractures, typically cause substantial blood loss before the casualty reaches the hospital level. By the time casualties with bilateral leg

amputations have reached the hospital level, they

have usually lost over half their blood volume and

may be agonal. Even casualties who have multiple,

small, soft-tissue extremity wounds may require

extensive procedures, with consequent considerable blood loss. During the Vietnam War, 16% of

casualties with extremity injuries received blood

transfusions; the most common volume transfused

ranged between two and five units.82

Depending on the severity of coexisting injuries,

these procedures can be prolonged, and caring for

the total patient, complex. Considerations include

hypovolemia, shock, bleeding, and poor intravascular access. Medical officers must be aware that

previously undiagnosed injuries may manifest

intraoperatively (eg, pneumothorax and refractory

hypovolemia secondary to occult fractures). Coexisting injuries include closed head injuries, cervical

spine injuries, thoracoabdominal injuries, burns,

and coagulopathies. Sepsis is always an impending

risk, and patient transport requires expertise to

avoid further injury.

Regional Anesthesia

Regional anesthesia is an attractive choice in the

appropriate casualty whose injury is localized.83,84

The advantages of regional anesthesia are (1) an

awake patient is able to control his or her own

airway; (2) the treatment team can perform sequential central nervous system examinations and further assess for occult injuries; and (3) the anesthesiologist can more accurately control the administered

dose of postoperative analgesia. The disadvantages are (1) the patient may lose control of his or

her airway and aspirate during surgery and (2)

severe hypotension may develop in the intravascularly depleted patient secondary to the induced

sympathectomy. Regional anesthesia is often not

indicated for the initial surgery because the surgery

tends to be prolonged and the patient will not

tolerate the immobility required. In addition, many

patients will require mechanical ventilation as part

of their medical management.85–89 A further consideration that applies to deployed hospitals (especially in OOTW when refugees are being treated) is

the likelihood of a language barrier between the

patient and the military anesthesiologist.

Intravenous regional anesthesia (ie, the Bier block)

is acceptable for simple fractures and surgery to the

forearm, wrist, and hand.90–93 The simplicity of the

technique, rapid onset, and minimal equipment

needs make for an attractive field anesthetic. The

disadvantages of brief duration and lack of postoperative analgesia detract from its use. Intravascular

overdose can occur if the local anesthetic is injected

too quickly near the tourniquet or if the tourniquet

deflates prematurely.

Reduction of simple fractures can be facilitated

by local infiltration of anesthetic into the hematoma.
Anesthesia and Perioperative Care of the Combat Casualty

514

is technically easy to perform. Sterility is mandatory: the hematoma is an excellent culture medium

for bacteria that may cause a subsequent

osteomyelitis.

Axillary block is simple and offers prolonged

anesthesia and postoperative analgesia. Inserting a

catheter into the axillary sheath allows subsequent

redosing to permit prolonged anesthesia. This technique is appropriate for procedures distal to the

elbow. The musculocutaneous nerve and the

intercostobrachial nerve diverge after the brachial

plexus is formed in at least 50% of the population

and, therefore, will need to be separately blocked if

a tourniquet is used. In addition, axillary blockade

has an effect beyond providing analgesia: by interfering with sympathetic nerve transmission, vasodilation and increased blood flow to the injured

extremity may be induced.

The management of the hypovolemic patient is

challenging in the face of continued bleeding that

will only be controlled by surgical hemostasis. The

use of ketamine can be considered while hemostasis

is achieved, but the anesthesia provider needs to

remember that ketamine is a potent myocardial

depressant in the patient whose sympathetic system is already maximally stressed. Some experienced military trauma surgeons consider ketamine

to be the anesthetic agent of choice for extremity

operations, especially when combined with a benzodiazepine.94 The uses and limitations of ketamine

are discussed in Chapter 10, Intravenous Anesthesia.

General Anesthesia

Overall, the military trauma anesthesia provider

needs to consider the casualty case load and balance

general anesthesia’s increased risk to the patient

but shorter induction time against other anesthetic

modalities that may be safer for the patient but take

longer to induce. A well-conducted general anesthetic utilizing whatever airway protection is reEXHIBIT 21-2

PURPOSES OF PULMONARY ARTERY CATHETERIZATION IN CASUALTIES WITH

EXTREMITY INJURIES

1. To measure cardiac output

2. To measure oxygen content of mixed venous blood

3. To assess hemodynamic indices:

• mean arterial pressure, with an arterial line

• cardiac index, with a pulmonary artery line

• stroke volume

• stroke volume index

• systemic vascular resistance

• left ventricular stroke work index

4. To measure derived indices in conjunction with other monitors such as oxygen consumption (VO2) by the

Fick method: cardiac output • (arterial oxygen content – venous oxygen content)

5. To measure filling pressures in the right side of the heart (CVP) and the left side of the heart (PAWP) to

assess for

• shock

• expected large volume shifts

• myocardial dysfunction

6. To continuously monitor mixed venous oxygen saturation

CVP: central venous pressure; PAWP: pulmonary artery wedge pressure

4.
Extremity Injuries

515

quired can be preferable to the potential complications of delaying surgery. The actual incidence of

gastric aspiration is small compared to the potential

risks of loss of function of an extremity.95 Early

fixation of severe fractures will decrease the incidence of fat embolism syndrome, deep venous

thrombosis, and continuing hemorrhage. The incidence of morbidity and mortality following femoral fracture has been decreased after early fixation,

allowing mobilization of the patient. Aggressive

treatment of these patients is warranted, as the risk

of deep venous thrombosis approaches 40% to 60%

in the immobilized patient, with pulmonary embolism at 5% to 10%.69,85,87,89,96

INTRAOPERATIVE MONITORING

Trauma patients may benefit from invasive monitoring to optimize their hemodynamic performance

(Exhibit 21-2). These patients require continuous

vigilance to detect new injuries, with simultaneous

monitoring of their arterial blood gases, hematocrit,

urinary output, electrolytes, and coagulation status. The anesthesiologist needs to monitor the surgical field to estimate coagulation and blood loss.

Temperature monitoring is vital as it is related to

coagulation, cardiac output, shock, and so forth. A

normothermic environment and warming fluids

and gases will help to maintain the patient’s temperature. Additionally, the anesthesiologist must

rely on clinical skills, as there is frequently is not

enough time to institute technologically advanced

monitoring. Wartime and civilian mass casualty

situations are examples where clinical skills are of

paramount importance.

Prolonged surgery should not be terminated on

the grounds that the patient has had too much

surgery without objective evidence of refractory

shock or hypothermia. The patient should not be

taken to the intensive care unit until the life-threatening injuries are corrected. In addition, the military trauma anesthesiologist should consider that

triage will be ongoing in mass casualty situations

during war or disaster. This is important, considering the previously mentioned decreases in morbidity and mortality seen with early fixation of fractures.

SUMMARY

Extremity injuries in combat casualties are

generally not immediately life threatening but are

the major cause of morbidity as measured in mandays lost. In addition, extremity injuries are

a frequent reason for disability separation or retirement of combat casualties. Most combat casualties with extremity injuries will have either a

wound involving only soft tissues or a wound that

involves soft tissue in addition to bone or, less

commonly, neurovascular structures. The principles of management involve control of hemorrhage, excision of dead or contaminated tissue or

both, and fixation of a fracture, if present, in a

position likely to lead to restoration of normal function when union occurs. Wound sepsis is by far the

most common complication that occurs with extremity injuries. Less common complications are

fat embolism syndrome, deep venous thrombosis,

compartment syndrome, and pulmonary embolism.

Because wounds of the extremities constitute so

large a fraction of the operative case load, expert

and expeditious anesthetic care of these casualties

is necessary to maximize the use of operating room

resources.

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Orthopedic Surgery. Philadelphia, Pa: FA Davis; 1980: 21–28.
Burn Injuries

521

ROGER L. WESLEY, M.D.*

Chapter 22

BURN INJURIES

*Formerly, Major, U.S. Army; Anesthesia and Operative Service, Department of Surgery, Brooke Army Medical Center, Fort Sam Houston,

Texas 78234; currently, Staff Anesthesiologist, Lewis-Gale Clinic, 1802 Braeburn Drive, Salem, Virginia 24153

INTRODUCTION

EARLY CARE

Data Collection

Fluid Resuscitation

Monitoring of Resuscitation

Maintenance of Peripheral Perfusion

Antibiotics

Tetanus Precautions

Gastrointestinal Precautions

Analgesia

Wound Care

PATHOPHYSIOLOGY OF BURN INJURY

Pulmonary Pathophysiology

Hemodynamic Derangements

Hematological Derangements

Metabolism and Nutrition

Immunological Changes

INHALATION INJURY

Carbon Monoxide Intoxication

Upper-Airway Injury

Lower-Airway Injury

Treatment

CHEMICAL AND ELECTRICAL BURNS

FLUID ADMINISTRATION AFTER RESUSCITATION

Hypertonic Saline

Colloids

Diuretics

EVACUATION OF THE BURN CASUALTY

PERIOPERATIVE CONSIDERATIONS

Preoperative Assessment

Preoperative Medications

Monitoring

Transport

Anesthetic Technique

Intraoperative Fluid Management

Temperature Regulation

Postanesthetic Considerations

SUMMARY
Anesthesia and Perioperative Care of the Combat Casualty

522

INTRODUCTION

Burn injury is both a predictable consequence of

modern combat and a challenge for military medical personnel. For several reasons, thermal injuries

will comprise a not-insignificant fraction of the

casualties of modern warfare, not only in the army

but even more so in the navy and air force1:

• The very nature of existing antipersonnel

and antitank explosive munitions such as

shaped-charge warheads makes thermal

injury likely.

• Secondary explosions and fires from the

fuels required for air and ground mobility

due to battle damage make thermal injury a

real possibility.

• Other weapons used in conventional warfare, such as fuel-air explosive bombs, which

are designed to injure by blast overpressure, can cause thermal injuries.

• Nuclear weapons produce extremely high

temperatures capable of producing severe

thermal burns at a great distance.

In fact, thermal burns will constitute a major portion of the injuries in nuclear warfare.2

Throughout this chapter, the term burn injury

refers to thermal injury caused by fire except when

chemical or electrical burns are specified. Combat

casualties with burns present challenges to those

caring for them: some unique to thermal injury, and

some common to severe trauma of other types. One

of the major distinctions between burned soldiers

and civilians is the propensity for soldiers to have

additional injures. Data from a World War II study

of tank casualties show that of the 50% of casualties

who were injured while in the tank and who survived to reach medical care, one half had penetrating injuries in addition to having been burned.3

Combat action is neither the only nor necessarily

the most important source of thermal trauma for

soldiers. Historically, nonbattle injuries resulting

from fires from vehicular accidents or aircraft crashes

have generated more burns than have combat action. Data from the Korean War illustrate this point:

1% of total admissions for combat injuries (766

soldiers) were for treatment of burns, while 7.3% of

admissions for with nonbattle-related injuries (5,510

soldiers) were for treatment of burns.4

Besides the immediate concerns of narrowing of

the upper airway, respiratory compromise, and

hemodynamic instability, the burn casualty can also

present with a host of problems including altered

fluid requirements, limited intravenous access and

monitoring sites, altered thermoregulatory response, hypermetabolism, and immunosuppression.

Other physiological perturbations affecting intensive care and anesthetic management include altered drug response, deranged pulmonary dynamics, altered hematological profile, malnutrition,

sepsis, and multiple organ failure.

Large numbers of burn casualties will place heavy

demands on both the medical personnel and the

logistics of the military medical system. A clear

understanding of the unique challenges presented

by such casualties is necessary for us most efficiently and effectively to use existing medical resources and capabilities through each echelon of

combat medical care.

The first step in battlefield burn care is to stop the

burning process by removing the source of the burn

injury: extricate the casualty from the burning armored fighting vehicle, ship, or aircraft; extinguish

the flame; remove the smoldering clothing; break

contact with the electrical current source; flush off

the offending caustic chemical. Immediate assessment of airway adequacy, respiratory exchange,

and hemodynamic stability follows. Then basic

life-support measures are begun, including cardiopulmonary resuscitation if indicated. Supplemental oxygen should be administered if available and

if the burn occurred in a closed space, as carbon

monoxide poisoning is likely.5 Extensive upperairway burns with resultant edema, obtundation,

inadequate ventilation, or associated severe facial

or chest trauma necessitate endotracheal intubation

and ventilatory support.

After cardiopulmonary stabilization, gross estimation of all injuries including extent and depth of

burn injury is made, and a clean dressing is placed

over the burns. If associated injuries are extensive,

blood loss is brisk, or time until definitive treatment

will exceed 30 minutes, intravenous access should

be secured, preferably via a large-bore peripheral

percutaneous cannulation, and a balanced salt solution administered.6 The casualty is then transported

to a location for more definitive examination and

treatment.

At the level of the medical company or battalion,

decisions will be made as to the further disposition

of the burn casualty. Because subsequent treatment

is based on the extent and severity of the burn and

associated injuries, a careful physical exam and
Burn Injuries

523

assessment of burn depth and percentage of body

surface involved should be performed at this echelon of care. Burn severity is described as partial

thickness or full thickness, based on the depth of

injury. Initially, burn depth may be difficult to

estimate correctly and the depth may even progress

over time from partial to full thickness.7 Superficial, partial-thickness burns range from erythematous sunburn to a devitalization of the superficial

layers of the epidermis with blister formation overlying a wet, red, hypersensitive, edematous skin

bed; this injury will heal spontaneously. Deeper

partial-thickness burns appear dry, waxy, and white

beneath the devitalized epidermis. These injuries

are sensitive only to deep pressure and will heal

with hypertrophic scarring if protected well. Fullthickness burns involve complete destruction of the

skin and appendages, and appear dry, leathery, and

somewhat translucent.8 Eventual excision and grafting are required for wound closure.

The extent of body surface area burned is an

important variable in delivering adequate fluid resuscitation, and is estimated by the “Rule of Nines”

(Figure 22-1). This involves assigning percentages

of total body surface area (TBSA) to various body

parts.1 Major burn injuries are considered to be

those consisting of partial-thickness burns of greater

than 25% of TBSA, full-thickness burns of greater

than 10% TBSA, or smaller burns (of hands, face,

feet, perineum) with complicating features (eg, inhalation injury, extremes of age, significant preexisting disease, or associated trauma).9

Current conventional burn care dictates that

major thermal injuries be managed in a specialized

burn treatment facility. Moderate, uncomplicated

burn injuries (ie, 15%–25% TBSA partial-thickness

burn or 2%–10% TBSA full-thickness burn) will

usually require hospitalization in a general hospital

that has some experience in burn care.7 Minor burn

injuries (ie, < 15% TBSA partial-thickness burn or

< 2% TBSA full-thickness burn) may be treated on

an outpatient basis. The Emergency War Surgery

NATO Handbook modifies these recommendations

and suggests that, to conserve medical resources in

Fig. 22-1. The “Rule Of Nines” for calculating total body

surface area burned: head and neck, 9%; anterior trunk,

18%; posterior trunk, 18%; upper extremity, 9%; lower

extremity, 18%; and genitalia and perineum, 1%. Reprinted with permission from Moylan JA. First aid and

transportation of burned patients. In: Artz CP, Moncrief

JA, Pruitt BA, eds. Burns—A Team Approach. Philadelphia, Pa: WB Saunders; 1979: 153.

EARLY CARE

initiated, analgesics administered, and burn wound

care initiated.

Data Collection

When the capability to do so exists, several data

need to be procured. These include the casualty’s

At the second or third echelon of care, and before

evacuation to a definitive burn care facility or general hospital with burn care experience, several

steps should be initiated: some important data collected, fluid resuscitation established and monitored, peripheral perfusion maintained, tetanus

prophylaxis provided, gastrointestinal precautions

times of mass casualties, casualties with burns of

less than 20% TBSA be treated either as outpatients

or via self-care in a minimal care facility. In addition, these casualties are removed from active combat. Those with burns of the head and neck, hands,

or feet, however, require hospitalization. Casualties with burns of 20% to 50% TBSA; or smaller

burns with associated blunt, blast, or penetrating

trauma, require hospitalization for definitive care

and ultimate surgical closure. Casualties with very

severe burns (ie, > 50% TBSA) are given minimal

care, based on their increasingly poor chances for

survival as the TBSA involved increases. They are

treated as time and resources allow.2
Anesthesia and Perioperative Care of the Combat Casualty

524

weight (for calculating resuscitation fluid requirements), followed by daily weights; baseline chemistry and arterial blood-gas studies; and a chest radiograph to assess pulmonary status, and as a baseline

for comparison with subsequent radiographs during the resuscitation and postresuscitation phases.

When thermal injury is complicated by other

nonthermal trauma (eg, blunt, blast, or penetrating trauma), other data should be accumulated.

These may include cervical spine or inhalation/

exhalation radiographs, hematocrit, gross urinalysis, or diagnostic peritoneal lavage cell count,

when indicated.

Fluid Resuscitation

Fluid management of the burn casualty presents

a particular challenge to the medical officer. Thermal injury necessitates aggressive, early fluid resuscitation. Burn patients exhibit a dramatic, early

intravascular/extravascular disequilibrium resulting from the loss of functional capillary integrity,

extravasation of intravascular fluid, resultant edema

formation, and loss of circulating blood volume.

Fluids are administered to restore blood and plasma

volume, and organ and tissue blood flow; increase

cardiac output; and decrease peripheral vascular

resistance.10 A number of resuscitation formulas

exist (Table 22-1), each consisting of crystalloid and

colloid volume guidelines for the first 48 hours after

the burn.

The widely used Modified Brooke Formula calls

for 2 to 4 mL of lactated Ringer’s solution to be

infused per kilogram of body weight per percentage of the total body surface area burned (2–4 mL/

kg/% TBSA) during the first 24 hours after the burn.

The rate of infusion of resuscitation fluid is increased or decreased within this range based on

clinical response. Occasionally with massive burns

exceeding 50% TBSA, the rate of 4 mL/kg/% TBSA

burned is not sufficient, and higher infusion rates (to

6 mL/kg/% TBSA burned) may be required. A

colloid-containing fluid equivalent to plasma may

be initiated at a rate of 0.3 to 0.5 mL/kg/% TBSA

burned during the second 24-hour period, along

with 5% dextrose in water at a rate sufficient to

maintain desired urinary output (which is discussed

later in this chapter).

Including colloids during the second 24-hour

resuscitation period may provide some oncotic benefit and allow more-effective restoration and maintenance of intravascular volume, since most pulmonary capillary integrity is reestablished by this time.

Five percent dextrose in water makes up the balance of the second 24-hour resuscitation fluids because a high sodium intake typically occurs during

initial resuscitation.

Monitoring of Resuscitation

Assessing the adequacy of resuscitation is accomplished by monitoring urinary output, blood

TABLE 22-1

RESUSCITATION FORMULAS FOR ADULT BURN CASUALTIES

Component Modified Brooke Parkland

First 24 Hours

Ringer’s lactate 2–4 mL/kg/% TBSA 4 mL/kg/% TBSA

Colloid — —

D5H2O— —

Second 24 Hours

Colloid 0.3–0.5 mL/kg/%TBSA 20%–60% of plasma volume

D5H2O Volume sufficient to Volume sufficient to

maintain urinary output maintain urinary output

D5H2O: 5% dextrose in water; TBSA: total body surface area.

Data sources: (1) Pruitt BA Jr. Advances in fluid therapy and the early care of the burn patient. World J Surg. 1978;2:139–150. (2) Baxter

CR, Shires T. Physiologic response to crystalloid resuscitation of severe burns. Ann NY Acad Sci. 1968;150:874–894. (3) Baxter CR.

Fluid and electrolyte changes of the early postburn period. Clin Plast Surg. 1974;1(4):693.
Burn Injuries

525

pressure, mental status, and, occasionally, cardiac

filling pressures. A Foley catheter has been described as the single best monitor of the adequacy of

resuscitation in patients with normal renal function

and an absence of congestive heart failure, pulmonary dysfunction, or history of shock. These criteria

probably describe the majority of burn combat casualties if the burn occurs without associated blast,

blunt, or penetrating injury. The target urinary

output is 0.5 mL/kg/h in adults and 1 mL/kg/h in

children who weigh less than 30 kg.11 Hypotension,

cardiovascular collapse, renal failure, progression

of burn depth, or mental status changes may result

from inadequate resuscitation. Overzealous fluid

administration can result in increased morbidity

and mortality from pulmonary edema and increased

peripheral edema, which can impair wound healing and convert a partial-thickness burn into a fullthickness injury.12

Several groups of patients have been shown to

require more than the standard amounts of resuscitation fluid. These include patients with

inhalation injuries, intoxicated patients, those

with electrical injuries, and those undergoing

delayed resuscitation.10,13 The Parkland Formula

(see Table 22-1) was originally developed for

patients with inhalation injuries and may also be

more appropriate for these other subsets of patients. Also, because pediatric patients may have

fluid needs not accurately predicted by most of

the weight-based formulas, their fluid resuscitation should be individualized.9 In every case, the

adequacy of resuscitation should be closely monitored, and fluids added or withheld based on the

desired response of adequate peripheral perfusion rather than strict adherence to a standard

formula.

Maintenance of Peripheral Perfusion

Because full-thickness, circumferential burns of

the thorax, upper abdomen, or extremities can lead

to loss of life or limb, early, aggressive care is

mandatory. Any item of clothing or jewelry must be

removed if it could potentially constrict and contribute to subsequent edema formation. Similarly,

escharotomy is necessary to prevent life-threatening ventilatory compromise, limb loss, or permanent damage to underlying neurovascular structures.14 Escharotomy is performed by incising

linearly at the midmedial and midlateral lines, down

to and just through the subdermal fascial attachments. Anesthesia is not usually required since

these deep burns are insensate.9

In other large burn injuries, peripheral pulses

should be checked at least hourly to assess perfusion as edema worsens. A Doppler flow detector is

useful to detect blood flow.

Antibiotics

As a general rule, prophylactic, systemic antibiotics are of no value in the management of burns.

However, the chapter on burn injuries in Emergency War Surgery recommends the administration of penicillin to all thermally injured combat

casualties (unless contraindicated) to prevent βhemolytic streptococcal burn wound infections.1

This recommendation, differing as it does from

civilian standards of practice, reflects both the different milieu in which combat injuries occur vis à

vis civilian trauma and the likely delay that will be

encountered in evacuating the casualty from the

battlefield to a fourth- or fifth-echelon burn center.

Penicillin is to be given for up to 5 days, after

which antibiotics are administered only if there are

signs of clinical infection or if burn sepsis is thought

to be present. When burn sepsis is thought to be

present, incisional biopsy is necessary to identify

the origin of the infection. Appropriate antibiotics

(eg, penicillin against β-hemolytic streptococcal

bacteria) are instituted when the causative organism has been verified by culture or there is a high

degree of clinical suspicion. In contrast to systemic

antibiotics,

[t]opical antimicrobial agents decrease the incidence of invasive infections in burns. Three effective chemotherapeutic agents that are frequently

used to treat burn infections are [mafenide acetate],

[silver sulfadiazine], and silver nitrate.15(p357)

Tetanus Precautions

Since all burn injuries are considered contaminated, tetanus prophylaxis is indicated except in

casualties who have been actively immunized within

the preceding 12 months. If a booster dose was

administered within the preceding 10 years, an

injection of 0.5 mL of adsorbed tetanus toxoid will

provide prophylaxis. If active immunization was

not done within 10 years before the burn, 250 to 500

units of tetanus immunoglobulin (human) should

simultaneously be administered at another site.16

Gastrointestinal Precautions

Since most patients with burns of more than 20%

TBSA develop a paralytic ileus during the first 24
Anesthesia and Perioperative Care of the Combat Casualty

526

hours after the injury, all oral intake is withheld and

a nasogastric tube is inserted for gastric decompression if not contraindicated by associated injury. In

addition, gastroduodenal ulceration is a frequent

complication of burn injury. First described by

Curling in 1842,17 these stress ulcers appear within

72 hours of the burn,18 have the potential to hemorrhage or perforate, and are associated with high

mortality rates.19 Curling’s ulcers occur with increasing frequency as burn size increases and, if not

prevented, appear in 40% of burns of 70% TBSA.20

Presumptive diagnosis is made on evidence of gastrointestinal bleeding, while definitive diagnosis is

by gastroduodenoscopy. Proper preventive treatment, which greatly reduces the incidence, involves

early control of gastric pH (to > pH 5) with antacids

or histamine 2 receptor antagonists (ie, H2 blocking

agents). Accordingly, antacids or H2 blocking agents

should be instituted via the nasogastric tube, or H2

blocking agents can be given intravenously.

Analgesia

Although full-thickness burns are insensate, partial-thickness burns or associated injuries can cause

marked pain, which further intensifies the neurohumoral stress response and may worsen morbidity and mortality. Administering small amounts of

intravenous narcotics such as morphine sulfate, or

partial narcotic agonists such as nalbuphine or

butorphanol, will lessen patient discomfort and

apprehension, as well as facilitate intravenous line

placement and early wound care.

Wound Care

Several objectives are important in early care of

combat burn wounds. Perfusion to the wound must

be maintained to supply needed tissue-oxygen levels.21 This is accomplished by providing hemodynamic stability, restoring circulating blood volume,

and performing escharotomy as needed. Remaining viable dermis must be protected in partialthickness burns by initially leaving large blisters

intact.22,23 Debris and devitalized tissue should be

removed from full-thickness burns21 and the wound

should be cleaned with soap and water. Since all

burn wounds are invariably contaminated, topical

antibiotics should be applied to the surface to temporarily retard bacterial growth and to help prevent

burn wound infection.22–24 Topical chemotherapy

may consist of sulfonamide cream, 0.5% silver nitrate solution, or mafenide acetate cream. Due to its

solubility in water, mafenide acetate burn cream

diffuses well into the burn eschar and may be the

best choice for limiting bacterial proliferation.6

PATHOPHYSIOLOGY OF BURN INJURY

Pulmonary Pathophysiology

Derangements in pulmonary physiology accompany all major burns, even in the absence of inhalation injury. These pulmonary manifestations are a

major cause of morbidity and mortality, and also

clearly worsen the manifestations of inhalation injury. Early in the course of injury, pulmonary

derangement is manifested by changes in lung capillary permeability, vasoreactivity, and ventilation.

Surface burns cause an increase in pulmonary vascular resistance, paralleling the increase in systemic

vascular resistance that occurs with hypovolemia.

Subsequently, vasoactive mediators such as histamine, serotonin, and thromboxane A2 are liberated

from the burn wounds and further increase pulmonary artery pressures.21 Concomitant hypoproteinemia and complement activation, with subsequent white blood cell aggregation and deposition

in the lung vasculature and release of proteolytic

enzymes and oxygen free radicals, produce dramatic increases in lung vascular permeability. This

may produce the classic radiological and hypoxemic condition known as adult respiratory distress

syndrome.25 Hypoxemia is worsened by elevation

of the closing volume (ie, the alveoli become unstable and collapse) and subsequent atelectasis.21

Ventilation is initially unchanged or decreased

as a result of hypovolemia, concomitant increase in

small-airway resistance, pain-induced splinting, or

narcotic-induced hypoventilation.21 Ventilation may

be severely depressed by electrical injury as a consequence of central nervous system depression or

from large increases in total lung compliance from

chest wall edema. If necessary, endotracheal

intubation and mechanical ventilation should be

instituted.

When adequate hemodynamics are restored, hyperventilation begins, with an increase in both tidal

volume and respiratory rate. This increase in ventilation, which is secondary to the demands of hypermetabolism, peaks at the second week after the

burn, subsequently declines to a level 2- to 3-fold

greater than normal, and then persists until wound
Burn Injuries

527

closure has been effected. Hyperventilation is accentuated by several factors including the presence

of topical mafenide acetate cream (which inhibits

carbonic anhydrase activity), sepsis, fever, anemia, pulmonary parenchymal disease, pain, and

anxiety.5

Hemodynamic Derangements

Early hemodynamic changes are due to deficits

in blood volume that are related to transvascular

loss of fluid, electrolytes, and protein. This

hypovolemia causes tachycardia and, when pronounced, reduction of cardiac output. Both systemic and pulmonary vascular resistance rise in

response to neurohumoral mediators, including

catecholamines. Cardiac filling pressures decrease,

which may further decrease the cardiac output.

Perfusion to the periphery is ultimately decreased,

but output to the viscera is maintained. A circulating myocardial depressant factor was previously

thought to be liberated in burn patients but has not

been definitively characterized to date. Positive

pressure ventilation can superimpose a further reduction in cardiac output. With adequate fluid

resuscitation, the cardiac output returns to normal

by the end of the first 24 hours after the burn

and then to supranormal levels thereafter.

Hyperdynamic changes persist until the wound is

closed.

Hematological Derangements

Hematological changes are manifested by early

destruction, injury, and loss of red blood cells. As

much as 8% to 19% of the red blood cell pool may be

destroyed by heat. Subsequent loss secondary to

wound debridement (as much as one unit every 3–

4 d), phlebotomy for frequent laboratory studies,

clearance of damaged red blood cells by the reticuloendothelial system, and decrease in hematopoiesis cause anemia that persists until the wound is

closed.11 In addition, free plasma hemoglobin and

hemoglobinuria can be seen shortly after the burn.21

Early anemia is often masked by plasma-volume

deficits that are proportionally greater than red

blood cell losses. Maintenance of blood volume is

important to minimize catecholamine release and

subsequent catabolic stress,11 since the hypermetabolic cardiovascular system is already stressed in

attempts to provide oxygen delivery.

Other hematological changes include early

leukocytosis and development of a hypercoagulable state, probably secondary to activation of clotting factors in the burn wound.21 Platelet count and

platelet adhesiveness increase for about 3 weeks.26

Factors V and VIII increase to levels 4- to 8-fold

greater than normal and remain elevated for 2 to 3

months. Fibrinogen levels are initially reduced,

then return to normal within 36 hours, and finally

remain elevated for as long as there is an open

wound (eg, 3 mo26). Fibrin split products may be

elevated for the first 3 to 5 days. A massive burn

may also be complicated by consumption of clotting factors, leading to a hypocoagulable state.21

Metabolism and Nutrition

After hemodynamic stability has been afforded

by adequate resuscitation, a period of hypermetabolism ensues, with increased utilization of substrate, accelerated tissue breakdown, and depletion

of lean body mass.27 The metabolic rate rises in

proportion to the extent of the injury and may be

twice normal. In addition, heat production and skin

and core temperatures rise secondary to central

thermoregulatory changes. Protein stores are utilized via hepatic gluconeogenesis pathways to provide glucose for burn wound metabolism. Thus,

increased energy substrate and nitrogen requirements must be met if large reductions in lean body

mass are to be avoided. Energy requirements may

exceed 2,000 kcal/m2 body surface area, while nitrogen requirements may exceed 15 g/m2.

10 The

goal should be to meet these nutritional demands as

soon as possible, preferably as soon as the gastrointestinal tract is functioning normally. Providing carbohydrate needs will minimize the nitrogen

losses. Fat, vitamins, minerals, and nitrogen will be

required. The enteral route is preferred for feeding,

as it is less expensive, physiologically closer to

normal, and may be associated with fewer complications than parenteral nutrition.28

Immunological Changes

The burn casualty’s immune function is globally

impaired. The mechanical barrier of the skin is

destroyed and humoral factors are decreased, as are

cellular immune responses including lymphocyte

and neutrophil activity, and the reticuloendothelial

system is impaired.5 In addition, casualties with

thermonuclear burns exhibit bone marrow depression with variable leukopenia, particularly of lymphocytes.2 Burn casualties, then, are particularly

susceptible to infectious complications.
Anesthesia and Perioperative Care of the Combat Casualty

528

INHALATION INJURY

Deranged respiratory physiology is both the result of inhalation injury and the end-organ response

to the generalized systemic insult. Inhalation injury is a major source of morbidity and mortality:

50% to 60% of all burn-related deaths are related to

inhalation injury, with most being due to carbon

monoxide intoxication.29 Two important facts are

associated with inhalation injury:

1. it is the single most important associated

injury that contributes to thermal burn mortality,11 and

2. the casualty may or may not have an associated thermal burn.

A high suspicion of inhalation injury should exist if

the burn occurred in a closed space such as a vehicle

or bunker, or if there are burns on the casualty’s face

or within the mouth or throat. Difficulty breathing,

singed facial or nasal hair, changes in the voice,

brassy cough, sooty or bloody sputum, or circumferential burns of the chest should alert the medical

officer that inhalation injury is likely.30 A radiograph of the chest is an insensitive, and sometimes

a misleading, indicator of inhalation injury. Confirmatory diagnostic studies including fiberoptic

bronchoscopy and xenon 131 lung scans are performed when available.

Inhalation injury has three components, each of

which may occur independently or concurrently:

(1) carbon monoxide intoxication, which is a consequence of incomplete combustion; (2) upper-airway injuries, which are caused by heat; and (3)

lower-airway injuries, which are caused by chemical vapors or fumes.

Carbon Monoxide Intoxication

Carbon monoxide intoxication produces severe

hypoxemia because carbon monoxide avidly binds

to the hemoglobin molecule, forming carboxyhemoglobin, which displaces oxygen, resulting in decreased blood oxygen saturation. This desaturation

is worse at the scene of injury as fire consumes

much of the available oxygen. Carboxyhemoglobin

also shifts the oxyhemoglobin dissociation curve to

the left. The result is decreased oxygen delivery to

the tissues, causing tissue hypoxia.31,32 Initial symptoms of carbon monoxide intoxication include

palpitations, headache, dizziness, and confusion.

Higher carboxyhemoglobin levels result in restlessness, excitement, and even unconsciousness

when the carboxyhemoglobin level rises above

40%.

Early administration of a high concentration of

inspired oxygen is important in treating carbon

monoxide intoxication. The half-life of carboxyhemoglobin is reduced from about 4 hours when

breathing room air to 30 minutes when 100% oxygen is administered.11 Treatment in a hyperbaric

chamber has been reported33 to be efficacious for

severe carbon monoxide poisoning.

Upper-Airway Injury

Because the heat-carrying capacity of air is quite

low, and hot vapors are rapidly cooled to body

temperature as they pass through the nasopharyngeal area and upper airway, direct heat injury usually only affects the upper airway.34 Heat injury

below the level of the upper trachea is rare except

with steam injury. Moreover, reflex closure of the

glottis often protects the trachea and lung parenchyma.35 Marked edema occurs in the mucosa within

minutes to hours after the burn; ulceration and

hemorrhage are also found in the mucosa. The

edema may be worsened by large amounts of fluid

given during resuscitation.36 The airways of patients with these conditions should be protected

immediately by intubation, even if only prophylactically, since the edema lasts several days and may

make late intubation difficult or impossible.

Orotracheal or nasotracheal intubation is preferable to tracheostomy because surgical airway manipulation is associated with high mortality.37

Lower-Airway Injury

Damage to the lower airway is usually in the

form of chemical tracheobronchitis resulting from

the liberation of water-soluble gases from burning

plastics and rubber. These gases—ammonia, phosgene, sulfur dioxide, and chlorine—cause epithelial

damage when converted to acids and alkali on contact with airway mucosa. Lipid-soluble toxins—

nitrogen oxides and aldehydes—are produced from

burning wood and destroy lipid cell membranes

and denature proteins. These toxins damage both

alveolar and capillary endothelium, which causes

increased permeability and pulmonary edema even

at normal capillary filling pressures. Ciliary paralysis and severe bronchospasm also occur. The

end result is plugged airways, obstructive and secondary atelectasis, relative hypoxemia, postobstruc-
Burn Injuries

529

tive emphysema, and occasionally complete lobar

collapse.35

Depending on the severity of the initial insult,

patients with lower-airway injury progress through

three clinical stages of injury. During the first 36

hours after the burn, acute pulmonary insufficiency

occurs, characterized by hypoxemia, tracheobronchitis, bronchospasm, cough, atelectasis, and pronounced upper airway swelling. The second stage

is pulmonary edema, which develops 6 to 72 hours

after injury. Pulmonary edema is seen in 5% to 30%

of patients and is associated with high mortality.

The third stage is bronchopneumonia, seen in 15%

to 60% of casualties, beginning 3 to 10 days after the

burn. Bronchopneumonia is associated with 50% to

80% mortality.38

Treatment

Treatment of severe inhalation injury involves

endotracheal intubation, mechanical ventilatory

support, supplemental oxygen, and aggressive tracheobronchial toilet including humidification, frequent suctioning, postural drainage, and repeated

bronchoscopy. Antibiotics are instituted for culture-proven pneumonia. Systemic steroids have

been found to be of no value except to treat

bronchospasm unresponsive to parenteral and inhaled bronchodilators.35 These patients’ high minute

ventilation requirements and reduced pulmonary

compliance increase their susceptibility to the complications of mechanical ventilators and place added

stress on conventional ventilators. Ventilators that

are capable of generating high minute volumes are

invaluable for intensive care and operating room

use for these patients. In addition, it appears that

high-frequency percussive ventilation is effective

in the treatment of patients with severe inhalation

injury.39

Increasing evidence indicates that oxygen-derived free radicals contribute to the pathophysiology of inhalation injury, especially in the period

beginning 24 hours after exposure. Studies40 carried out in a laboratory model of inhalation injury

show that airway injury was markedly reduced by

instillation of the iron-chelating agent deferoxamine

complexed with pentastarch. Free iron, which is

removed by deferoxamine, is known to catalyze the

formation of such reactive species as the hydroxyl

radical. Interventions based on these observations

may have important therapeutic implications in

human victims of smoke inhalation.41

CHEMICAL AND ELECTRICAL BURNS

Chemical burns to the skin and lungs, and the

serious respiratory problems that arise when chemical warfare agents such as mustard and phosgene

are inhaled, are described in Chapter 30, Anesthesia

for Casualties of Chemical Warfare Agents. Chemical burns caused by acid or alkali have a component

of injury caused by heat that is released when the

chemical contacts the tissue. The severity of the

burn is related to both the duration of exposure and

the concentration of the chemical.14 In general,

burns from strong alkalis are more severe than

those from strong acids, since the alkalis bind more

avidly to the tissues and are therefore more difficult

to remove. Initial treatment lies in expedient removal of the chemical by copious water lavage of all

exposed surfaces, after all the casualty’s clothing

has been removed. The prolonged use of cold water

and subsequent hypothermia should be avoided, as

this increases morbidity. Neutralizing agents should

be avoided since their use may liberate more-intense heat. Severe chemical burns may appear

deceptively superficial in the initial stages.5

Although electrical burns are uncommon among

combat casualties, military anesthesiologists need

to know about this entity, with its distinctive appearance and unique associated injuries, fluid requirements, wound care, and complications. Electrical injury is arbitrarily categorized into burns

caused by low-voltage sources (< 1,000 volts) or

high-voltage sources (> 1,000 volts). High-voltage

burns are associated with substantial morbidity

and mortality: of patients who survive to reach the

hospital, mortality may approach 3% to 15%.42

The tissue’s resistance converts electromagnetic

energy to thermal energy, which damages tissue.6

In addition, electrical injury may cause cardiac irritability or even asystole. Associated injuries are

common, including bone fractures (from falls or

severe, sudden muscular contraction); neurological

damage, which may be progressive (since electrical

current may flow through low-resistance neurovascular bundles); ruptured organs; or unexpected

and widespread destruction of any soft-tissue structure.11,26 In fact, an unimpressive wound may overlie large areas of devitalized tissue; this may lead to

underestimating the required resuscitation fluid.

Muscle burned by electricity may progress to

myoglobinuria and acute renal failure if additional

fluids and diuretics are not administered to induce

a brisk diuresis. This type of injury may cause
Anesthesia and Perioperative Care of the Combat Casualty

530

edema to occur beneath the investing fascia, which

requires fasciotomy rather than escharotomy.6

Initial wound care involves removal of the patient from the electrical source. Unconsciousness,

which necessitates intubation and mechanical ventilation, may result from high-voltage injury, as can

seizure activity. Along with the thermal damage,

electrical injury may cause cardiac arrest, requiring

cardiopulmonary resuscitation at the scene. Further treatment involves hemodynamic stabilization;

close monitoring; and early tissue exploration for

debridement, assessment of tissue viability, and

determining the need for amputation.6

Complications, which may be unpredictable, include cataracts; recurrent gastrointestinal dysfunction with a high incidence of cholelithiasis, hemorrhage, or prolonged ileus; immediate or delayed

spinal cord damage; peripheral nerve deficits;

delayed hemorrhage from large vessels; and

causalgia.6,26 The most common complication in the

hospital is the need for major amputation, which

occurs in 25% to 68% of patients.42

FLUID ADMINISTRATION AFTER RESUSCITATION

Vigorous fluid resuscitation causes abnormal

expansion of total body water and salt. Thus, the

postresuscitation burn casualty’s weight may substantially exceed his or her normal weight. A gradual

loss of the perhaps 15% to 20% gain in body weight

should be accomplished by a 2% to 3% weight loss

per day, so as to reach preburn weight by the 10th

day after the burn. This is accomplished by reducing the fluid rate by 25% per hour for patients who

maintain adequate urinary output.10 Initial salt

loading and subsequent high evaporative losses

may predispose the burn patient to hypernatremia,

so 5% dextrose in water is used to maintain serum

sodium at 140 mEq/L.

Hypertonic Saline

The use of hypertonic saline as a component of

the resuscitation fluid may be efficacious for patients in whom it is desirable to limit the total

volume of resuscitation fluid. Hypertonic saline

may cause less wound edema and may be particularly useful in patients with inhalation injury, circumferential full-thickness burns of the extremities, or intracranial injuries where massive fluid

accumulation could be catastrophic.9

 In addition,

hypertonic saline may be desirable for patients with

limited cardiopulmonary reserves (ie, the very old

or the very young) and those with cardiopulmonary

disease.10 However, no study has demonstrated

that any particular sodium concentration is superior for improving survival in burn patients.9 Moreover, the critical factor in administering hypertonic saline is the development of hypernatremia;

serious complications may result if serum sodium concentration rises above 160 mEq/L. Only

very experienced clinicians should use hypertonic saline.11

Colloids

During the first 12 to 24 hours after the burn, the

diffuse capillary leakage allows colloid fluid to

extravasate through the endothelial junction, preventing any demonstrable oncotic benefit over crystalloid fluid.11 Thereafter, capillary integrity is reestablished, and most resuscitation formulae include

colloidal solutions as integral components of fluid

therapy.

Diuretics

Diuretics are not included in burn resuscitation,

except for a few special classes of patients. These

include patients who have large, high-voltage electrical injuries; burns involving muscle; burns associated with large, soft-tissue injuries; and massive

burns, who remain oliguric despite adequate fluids.

Patients in this last category may be predisposed to

acute renal failure secondary to large amounts of

hemochromogens in the urine. A brisk diuresis is

desirable in these patients.

EVACUATION OF THE BURN CASUALTY

Despite the implementation of Medical Force

2000, which focuses on enhancing far-forward surgical care, increasing intensive-care capability in

the combat zone, and returning soldiers to duty as

soon as possible, a large proportion of burn patients

will be evacuated and transported. Forward surgical teams, field hospitals, combat support hospitals,

and mobile army surgical hospitals will not be

equipped to handle definitive surgical burn care.

The extensive blood loss, larger surgical manpower

requirements, and lengthy period required for skingraft maturation would place too great a burden on
Burn Injuries

531

EXHIBIT 22-1

BURN INJURY EVACUATION CHECKLIST

Patient Data Preburn weight

Preevacuation weight

Allergies

Medical history

Medications

Time of last oral intake

Vital signs chart

Laboratory Values ABG Blood type

UOP Electrolytes

CXR Other

Burn Data % TBSA burn

Facial burn?

Airway: intubated/nonintubated?

Inhalation injury suspected?

Summary of early care

Locations, types of catheters and IV lines

Equipment Fluids: Ringer’s lactate, D5H2O, albumin

Airway management: ET tubes, masks, laryngoscopes, O2,

positive-pressure breathing circuit or mask-valve-bag device

Analgesics

IV administration sets

these military healthcare resources. Therefore, casualties will be evacuated to a general hospital with

burn care capability and experienced personnel, or

to a specialized burn care center. However, there

are several associated risks and challenges.

The evacuation process may be accomplished

very early in the course of injury, be lengthy, and

occur when only minimal medical care can be provided. All these factors have particular impact on

the burn casualty, since evacuation may occur while

critical fluid requirements must be met, when tissue

edema may compromise the airway or associated

complicating factors (eg, inhalation injury; preexisting cardiorespiratory disease; blunt, penetrating,

or blast trauma) may impact heavily on the burn

casualty’s medical management and survivability.

The anesthesiologist, who may be the last healthcare

provider to see the casualty before the lengthy evacuation, can play a key role in reducing the burn

casualty’s morbidity and mortality.

The anesthesiologist must ensure adequate

preparation and communication before evacuation. Preparation involves ensuring that all patient data and records are clearly documented

and that adequate airway equipment, resuscitation drugs, and intravenous fluids are assembled.

Communication must be clear to both the evacuation team and the receiving burn care team.

These objectives are most efficiently accomplished by using a burn injury–evacuation checklist (Exhibit 22-1), which must be completed and

included with the casualty.

PERIOPERATIVE CONSIDERATIONS

Early excision and grafting of small burn wounds

is considered the norm. Since early excision and

grafting of large burns (> 30% TBSA) have been

shown to decrease mortality in patients aged 17 to

ABG: arterial blood gases; CXR: chest X ray; D5H2O: 5% dextrose in water; IV: intravenous; ET: endotracheal; UOP: urinary

output; TBSA: total body surface area
Anesthesia and Perioperative Care of the Combat Casualty

532

30 years,43 these surgical procedures are being accomplished earlier and earlier in the postinjury

course. This may pose several challenges for the

anesthesiologist, particularly if surgery is planned

during the resuscitative phase or if associated injuries are present.

Preoperative Assessment

Preoperatively, the military trauma anesthesiologist should review the history of the current

injury, including the amount of associated TBSA

burn, elapsed time since injury, and associated traumatic injuries. Concomitant medical problems,

chronic and recently instituted medications, family

history, postsurgical and postanesthetic history,

drug allergies, transfusion history, time since last

oral intake, and presence of intravenous lines and

invasive monitors should also be assessed. Current

vital signs, including hemodynamic data from

invasive monitors, should be noted along with

present and preburn weight and laboratory data,

including hematology, acid–base status, coagulation profile, liver function tests, and electrolytes.

The casualty’s electrocardiogram and a recent chest

radiograph should be reviewed. A physical exam

with emphasis on airway, pulmonary, and cardiovascular assessment is important. Evaluation

of any concomitant trauma should proceed as

indicated.

Preoperative Medications

While an individualized approach to each casualty should be used for preoperative medication,

several goals should be met: anxiolysis, sedation,

analgesia, amnesia, antisialagogue effect, elevation

of gastric-fluid pH, and reduction of gastric volume.44 Based on the patient’s hemodynamic stability, degree of apprehension, discomfort, personal

preference, and planned procedure, rational choices

for premedications can be made.

With few exceptions, medications that are being

administered before surgery are continued. In particular, medications that support hemodynamics

(eg, inotropics, vasodilators, and antidysrhythmics)

are continued, as are antibiotics and hyperalimentation fluid. In terms of sedation, critically ill patients may not tolerate depressant medications. An

amnestic agent such as scopolamine may be given

to these patients. Other seriously ill and intubated

patients may be receiving narcotics, sedatives, and

nondepolarizing muscle relaxants. If so, intravenous narcotics or benzodiazepines can be administered to facilitate patient comfort during transfer

and transport.

Patients who are more stable may be given small

amounts of intravenous narcotics or benzodiazepines, or, for patients who prefer an oral

premedicant, diazepam or lorazepam orally 1 to 2

hours before induction. For patients being given a

ketamine-based anesthetic, a deeper level of sedation is provided in the form of oral diazepam 1 to 2

hours before induction, followed by intravenous

diazepam or midazolam on induction. This reduces

the incidence of undesirable reactions when the

patient emerges from anesthesia. Glycopyrrolate is

given for its potent antisialagogue effects if a

ketamine anesthetic is planned, or if airway manipulation dictates a secretion-free field. The use of

other antisialagogues is discouraged; owing to the

crossing of the blood–brain barrier, they interact

poorly with ketamine.

Owing to their tendency to form Curling’s ulcers,

most burn patients will be given an H2 blocking

agent or a sucralfate regimen. If so, this is continued perioperatively. If not, oral or intravenous

ranitidine, famotidine, or cimetidine is administered. If the patient has been on particulate

antacids, these are discontinued 6 to 8 hours

before induction. For emergent surgery, an oral,

nonparticulate antacid such as Bicitra (sodium citrate and citric acid, manufactured by Baker Norton

Pharmaceuticals, Miami, Fla.) administered 15 to 30

minutes before induction is nearly 100% effective in

elevating the gastric fluid pH above 2.5.44 Metoclopramide speeds gastric emptying and is effective

if given orally 30 to 60 minutes before induction; the

effect is seen much quicker if administered intravenously.

Monitoring

Burn casualties can pose major challenges in placing and maintaining appropriate monitors. Adequate intraoperative monitoring is especially important considering the potential for extensive blood

loss, the frequent changes of position, and the duration of surgery. The monitors that are considered

essential for burn casualties are those that ensure

the adequacy of oxygenation and ventilation, including continuous pulse oximetry, end-tidal carbon dioxide monitoring, peak airway pressure, and

frequent arterial blood-gas analysis. Other routine

intraoperative monitors should include a continuous electrocardiograph (ECG); an automated blood

pressure cuff; esophageal, nasopharyngeal or rectal

temperature-monitoring devices; inspired oxygen
Burn Injuries

533

tension–monitoring devices; a peripheral nerve

stimulator; and precordial or esophageal stethoscopes. Lack of unburned tissue may necessitate

placement of needle ECG electrodes, use of a “backpack” ECG pad, or even an esophageal ECG lead.

Pulse oximetry probes can be placed on any finger,

toe, lip, tongue, ear lobe or helix, or ala nasi. Blood

pressure cuffs may be placed on the upper arm,

thigh, or calf, and may be sterilized and placed over

burned or grafted skin intraoperatively, as needed.

For more critically injured patients and those

with preexisting severe systemic disease, moreinvasive intravenous lines or monitors are placed.

A Foley catheter, arterial line, central venous catheter, or pulmonary artery catheter may be placed as

indicated. Frequent arterial blood-gas and hematocrit determinations must be made.

Adequate intravenous access must be established

before a major excision. This should include two

large-bore peripheral intravenous lines or one peripheral and one central line. If lack of access necessitates placing an intravenous line through burned

or grafted tissue, a meticulous sterile field must be

maintained. Equipment for rapid infusion of crystalloid resuscitation fluid and blood should be at

hand. Anesthesia providers may utilize a pneumatic pressure infuser powered by a pipeline oxygen source that can be regulated to achieve flow

rates up to 250 mL/min. If pressure devices are

used for intravenous infusions, care must be taken

to ensure that air is not infused inadvertently.

Transport

Monitoring and therapy must not be compromised while critically ill, burn casualties are transported to and from the operating room. Appropriate preparation includes notifying the intensive care

nurse well in advance of the need for organizing

lines and tubes. The casualty is counselled again,

reassured, and given additional premedication as

the level of apprehension warrants. A mechanical

lifting device can be used to move the patient from

the bed to a stretcher. A portable oxygen tank and

a disposable positive-pressure breathing circuit are

used for ventilation, except when precluded by

extremely high minute ventilation or elevated peak

airway pressures. In these cases, a portable transport ventilator is used, accompanied by a respiratory therapist. A portable suction device should be

available for casualties who require frequent

suctioning.

The monitors considered routine for transport

are a precordial stethoscope and a portable pulse

oximeter. A portable ECG monitor with an arterial

line channel should be available for more unstable

patients. Care must be taken with all lines and

invasive monitors, which, if tenuous, should be

sutured into place. A free-flowing intravenous line

is imperative, since resuscitative drugs might be

given during transport. Continuous-infusion devices are attached to the delivery pole on the

stretcher, so that any cardioactive medications or

hyperalimentation fluids can be continued.

Anesthetic Technique

The choices for the optimum anesthetic technique to use for the burn casualty are varied; however, rational decisions can be made based on known

physiological responses to our interventions. Regional anesthesia, although desirable in certain

cases, generally is avoided in burn casualties for

several reasons:

• The burn may cover the site of anesthetic

block placement, and it is undesirable to

expose the patient to the risk of central

neuraxis infection from colonized burn

wounds via spinal or epidural needle

placement.

• Excision or grafting procedures are accompanied by large fluid shifts and blood loss,

and the loss of sympathetic tone resulting

from a regional block may be undesirable.

• These casualties will likely undergo procedures at multiple excision and donor sites,

including both upper and lower body sites

at a single operation.

• In addition, an awake patient’s comfort is

frequently difficult to maintain during

lengthy excision and grafting procedures.

Induction and the Compromised Airway

Induction of general anesthesia is accomplished

on the operating room table, except when the initial

excision or graft harvest is on the patient’s posterior

surface. In that case, induction proceeds on the

stretcher, with subsequent positioning of the patient in the prone position. Choices for induction of

general anesthesia depend on associated hemodynamic instability, presence or absence of intravenous access, and airway status. For the

nonintubated patient, a combination of preoxygenation, midazolam, a narcotic, sodium

thiopental, and a large dose of nondepolarizing

muscle relaxant is frequently used. Although
Anesthesia and Perioperative Care of the Combat Casualty

534

ketamine has been advocated as a better induction

choice in hypovolemic patients, this impression has

not been proven. Etomidate is an effective induction agent that offers substantial hemodynamic stability, and is a good choice for patients when cardiac depression would be undesirable. While both

ketamine and etomidate both support hemodynamics well, military anesthesiologists must be aware

that maximally stressed patients may exhibit hemodynamic deterioration on induction due to some

degree of myocardial depression or loss of sympathetic tone. Propofol is a satisfactory induction agent in young, physiologically stable burn

patients.

Inhalation induction using halothane, isoflurane,

or enflurane, with oxygen and nitrous oxide is another option. Small doses of sodium thiopental (1–

2 mg/kg) may provide better tolerance for the

irritating vapor. After induction, the ability to

ventilate by bag is demonstrated. An intubating

dose of a nondepolarizing muscle relaxant may

be given at this time to improve conditions for

airway instrumentation.

The burn casualty may well have a compromised

upper airway, secondary to airway burns or to

massive peripheral edema secondary to burns elsewhere. Upper-airway obstruction is a life-threatening complication that appears in the first 36 hours

after injury.45 Large volumes of resuscitation fluid

may accentuate supraglottic edema, and concomitant facial and neck burns, constricting dressings,

and edema make mask ventilation and airway instrumentation difficult. Later in the course of hospitalization, airway management may be compromised by limited neck extension or mandibular

mobility. Lastly, airway management in the burn

casualty, both early on and later in the course of

treatment, may be difficult and be dictated by concomitant nonthermal trauma (eg, mandibular or

facial fractures) that will require individualized

approaches.

Several options exist for patients with a compromised airway. An awake intubation may be performed before anesthetic induction using topical

airway anesthesia via a blind nasal approach, direct

oral laryngoscopy, fiberoptic laryngoscopy, or a

lighted stylet (light wand) technique. If airway

difficulty is not anticipated, and a full stomach or

predisposition to gastroesophageal reflux exists, a

modified rapid-sequence induction using preoxygenation, intravenous induction using a large

dose of nondepolarizing muscle relaxant, ventilation through cricoid pressure, and rapid intubation

via direct laryngoscopy or light wand technique is

used. If the patient’s airway is not compromised,

and if the patient’s stomach is empty, then an inhalation induction can be followed by the airway

instrumentation of the anesthesia provider’s choice.

In situations where anatomical alterations suggest

difficulty, alternate measures should be at hand,

including the ability to perform emergent cricothyroidotomy, tracheostomy, or retrograde translaryngeal guidewire technique.

Maintenance of Anesthesia

No specific anesthetic agent is contraindicated in

the burn patient except succinylcholine, which can

trigger a potentially fatal hyperkalemic response

and is discussed later in this chapter. A wide

variety of anesthetic agents can be used satisfactorily. The burn patient’s altered pharmacokinetic

and pharmacodynamic responses, combined with

the nature of the physiological insult and the type of

surgery planned, dictate the choice of maintenance

drugs.

Intravenous Anesthesia. Ketamine, a popular

anesthetic for patients with thermal burns, produces sedation, profound analgesia, and a dissociative anesthetic state resulting from functional and

electrophysiological disruption of the association

between the thalamocortical and limbic systems.46–49

(The use of ketamine is also discussed in Chapter

10, Intravenous Anesthesia.) This drug has been

described as the only available intravenous agent

that can function as a sole anesthetic, without requiring adjunctive agents, owing to its unique combination of amnestic, analgesic, and anesthetic properties. Ketamine has particular application in the

critically ill patient, where a period of hypotension

or apnea could be life threatening.50 Ketamine produces a dose-related rise in the heart rate–blood

pressure product and supports hemodynamics

through direct stimulation of central nervous system structures.51 Although ketamine does have

some direct myocardial depressant and vasodilatory

effects, it will help maintain blood pressure in hemorrhagic and septic shock.52 Ketamine maintains

respiratory response to carbon dioxide (ie, the respiratory rate is proportional to the carbon dioxide

level), precluding significant respiratory depression except when given in a rapid intravenous bolus

of more than 3 to 4 mg/kg. Similarly, ketamine

effects an increase in pulmonary compliance with a

decrease in airway resistance and bronchospasm.

This effect is probably mediated by vagolytic and

direct, smooth-muscle, relaxant effects rather than

through beta receptors. Oral and bronchial secre-
Burn Injuries

535

tions are stimulated by ketamine, necessitating pretreatment with an anticholinergic agent. While

pharyngeal and laryngeal reflexes are preserved to

some degree,53 pulmonary aspiration of gastric contents can occur,54,55 and careful airway management

is necessary.

Ketamine has been associated with anestheticemergence delirium, which occurs after 5% to 30%

of surgeries performed under ketamine anesthesia.50 This delirium is characterized by vivid dreams,

hallucinations, dysphoria, and a sensation of floating in space. The incidence of this reaction can be

decreased by (a) preoperative counselling concerning the expected side effects and (b) pretreatment

with benzodiazepines. Oral diazepam, 0.15 mg/kg,

administered 1 hour before induction, followed by

0.2 to 0.3 mg/kg intravenous diazepam, or 0.05 to

0.14 mg/kg intravenous midazolam, administered

just before induction, is effective. Tolerance to the

analgesic effects of ketamine occurs with repeated

exposure to the drug.56

Balanced Anesthesia. A narcotic-based, balanced

anesthetic technique is an option for stable

intraoperative hemodynamics, smooth emergence,

and easily titratable levels of postoperative analgesia. The technique most commonly used at the U.S.

Army Institute of Surgical Research Burn Unit consists of fentanyl, sufentanil, or alfentanil administered either in incremental boluses or by continuous infusion, in combination with oxygen, nitrous

oxide, and low concentrations of inhaled vapor.

Burn patients may have increased narcotic requirements.57,58 This may be due to both pharmacokinetic

and pharmacodynamic factors,59 but perhaps is due

specifically to altered responses to the endogenous

opioids that are actively released during the stress

of thermal injury.60,61 In selected patients, morphine

is also an attractive choice for use before emergence, because its slower elimination will effect

longer postoperative analgesia. Respiratory depression, skeletal-muscle rigidity, and the development of tolerance with repeated use must all be

considered with any narcotic.

Inhalational Anesthesia. The four currently used

volatile inhalational anesthetics—halothane,

isoflurane, enflurane, and desflurane—produce satisfactory anesthesia for burn casualties, and may

have particular efficacy in those with inhalation

injuries. The inhalation agents all act at various

sites to prevent or reverse the bronchoconstriction

that may accompany inhalation injury. The mechanisms of action are probably (a) suppression of

airway reflexes and (b) direct, smooth-muscle relaxation (through action on the calcium flux in tracheal

smooth-muscle cells, which interferes with excitation–contraction coupling).62 To some extent, inhalational anesthetics reverse the hypermetabolic and

hyperdynamic state of burn patients.63 Both

halothane and enflurane tend to decrease cardiac

output and oxygen demand to approximately an

equal degree, thus maintaining the oxygen supplyand-demand balance.64 To date, halothane hepatitis

has not been described in patients with burns, even

after repeated exposure.65

Some investigators have voiced their concern

over the suppression of the immune response by the

combination of major surgery and inhalational

agents: bone marrow suppression by nitrous oxide66; reduced phagocytic function by halothane;

and reduction of lymphocyte reactions to antigens.67

However, most researchers believe that depressed

immunocompetence is not caused by the anesthetics but is the effect of the stress of the surgery itself.63

The potential exists that volatile anesthetics will

interact with topical epinephrine that has been applied to the exposed capillary bed following burn

wound excision to help achieve hemostasis.

Halothane, and to a lesser extent isoflurane and

enflurane, do sensitize the myocardium to both

endogenous and exogenous catecholamines.68–70 In

fact, plasma catecholamine levels up to 10-fold

higher than normal have been measured in such

circumstances.71 However, various studies show

minimal changes in cardiovascular parameters and

an absence of arrhythmias after topical epinephrine

during burn surgery.72,73 This apparent normalcy

may be due to the preexisting, injury-induced, elevated level of circulating catecholamines that burn

patients have, which leads to a decrease in the

number of receptors and a downregulation of the

receptor affinity.71,74–76

The burn patient’s response to neuromuscular

blocking agents is perhaps the most striking of all

altered drug responses, and is the most familiar to

anesthesiologists. As was mentioned earlier, these

patients can have a potentially fatal hyperkalemic

response to depolarizing muscle relaxants (ie,

succinylcholine). The release of massive amounts

of potassium by muscle cells is related to the dose,

the extent of burn injury, and the time elapsed after

the burn.77 Succinylcholine, then, may be used

safely in the first 24 hours after the burn but, in a

patient with a burn exceeding 10% TBSA, should be

avoided for the subsequent 18 months.

78 The mechanism of action is an increased sensitivity of the

muscle membrane secondary to a proliferation of

extrajunctional receptors, similar to that seen in

patients with degenerative neurological disorders.78
Anesthesia and Perioperative Care of the Combat Casualty

536

This response begins within days of the burn and

may persist for as long as 18 months after the burn.79

If succinylcholine is inadvertently administered,

then calcium chloride, a therapeutic mixture of glucose and insulin, and sodium bicarbonate should be

administered, along with cardiopulmonary resuscitation, if cardiac arrest results. Calcium chloride

should be subsequently continued until peaked T

waves in the electrocardiographic tracing return to

normal.59

Resistance to nondepolarizing muscle relaxants

has been well documented with respect to anesthetics such as metocurine,79,80 pancuronium, 81,82

alcuronium,83 d-Tubocurarine,84,85 and atracurium,86,87 and is likely to be encountered with all

competitive agents.86 (This topic is also discussed in

Chapter 11, Neuromuscular Blocking Agents.) The

mechanism of this resistance may be alterations

both in the pharmacokinetics of the relaxant and at

the neuromuscular junction. Pharmacokinetic factors may involve increased plasma-protein binding, depressed hepatic metabolism, and changes in

blood flow that cause lengthened equilibration time

between the relaxant in the plasma and in the neuromuscular junction, causing an artifactual rightward shift in the dose-response curve. Possible

alterations at the neuromuscular junction include

an increase in the number of acetylcholine receptors, decreased cholinesterase levels, or some type

of prejunctional pathology. Clinically, this resistance is manifested as an increase of 2- to 5-fold in

the requirements for both dosage and serum concentration over that of patients who are not burned.

Despite this resistance, there appears to be no prolongation of recovery time or difficulty with reversal of the relaxants.88 The altered response to

nondepolarizing agents has been shown to persist

for as long as 463 days.81

Intraoperative Fluid Management

Casualties with burns pose particular challenges

with respect to fluid management. Thermal injury

necessitates aggressive, early fluid resuscitation,

and, for reasons unconnected to the burn, the casualty may require surgery and anesthesia at any

phase of resuscitation. Continued derangements in

fluid and electrolyte balance continue in the

postresuscitative phase.

Intraoperative fluid therapy for excision and

grafting procedures involves very rapid infusion of

crystalloid, colloid, and packed red blood cells. The

loss of one or more blood volumes is not unusual in

a major tangential excision. Pressure infusion devices are necessary, as are efficient blood- and fluidwarming devices.

Thermally injured patients frequently present

for anesthesia and surgery with anemia that is caused

by heat-induced lysis of red blood cells, reduced

erythropoiesis, or frequent blood drawing. Early in

thermal injury, anemia may be masked by a loss of

plasma volume that exceeds the loss of red blood

cells. Transfusion of red blood cells may therefore

begin before excision if extensive blood loss is anticipated. Moreover, the adequacy of tangential

excision is demonstrated by a briskly bleeding capillary bed. Large amounts of blood may be lost

before hemostasis, and estimating this loss is difficult because surface oozing is difficult to collect in

a suction device and the blood ends up in soaked

gauze; on the drapes; or on the floor, sometimes

under the operating room table. Visual estimation,

heart rate and blood pressure, urinary output, and

perhaps central venous pressure or cardiac filling

pressures, all help guide the need for blood replacement. Hematocrit measurement made while blood

loss is ongoing is of questionable value.

Because of associated potential risks, including

disease transmission and the risk of transfusion

reaction, homologous blood transfusion today

should be justified only by the need for increased

oxygen delivery. However, the burn patient may

require a higher hematocrit than a patient who is

not burned, secondary to elevated oxygen delivery

requirement in the face of hypermetabolism, inability of an already stressed cardiovascular system to

compensate for anemia, and reduced hematopoiesis.89 While maintenance of hematocrit values in the

low to mid twenties may be adequate for an otherwise physiologically healthy burn patient, the presence of concomitant physiological impairment may

effect a need for a somewhat higher target hematocrit (ie, in the range of 0.30–0.35).

Temperature Regulation

Paradoxically, hypermetabolic patients whose

central thermoregulatory set point is elevated are

especially susceptible to hypothermia during anesthesia and surgery. Thermally injured patients

have a propensity for abnormal heat loss secondary

to the burn itself, the nature of the surgical procedure, the temperature of the operating room, and

general anesthesia. Burn injury accentuates heat

loss of all kinds, especially evaporative loss, which

accounts for most of the difference in heat loss

between burned and unburned patients.90 Losses

from conduction and convection are also increased90
Burn Injuries

537

since considerably large areas of body surface are

often excised or prepared for donor sites, and large

areas of body surface are exposed in the operating

room.

General anesthetics cause increased heat loss via

several mechanisms. Dry anesthetic gases cause

evaporative water and heat loss from airways.

Anesthetics cause a loss of ability to preserve core

temperature through cutaneous vasoconstriction

and shivering. Specifically, inhalational agents

cause a 15% decrease in the basal metabolic rate,90

promote surface blood flow, and promote hypothermia through effects on central thermoregulatory centers.91 A narcotic–nitrous oxide anesthetic

decreases metabolic oxygen uptake (VO2) by 50%,

while ketamine has been shown not to alter VO2.

92

In addition, neuromuscular blocking agents prevent shivering and lower the metabolic rate.

Decreases in core temperature produce several

intraoperative and postoperative problems. Hypothermia can depress cardiac output, induce dysrhythmias, abolish hypoxic pulmonary vasoconstriction, shift the oxyhemoglobin dissociation curve

to the left, and depress hepatic and renal functions.93 A clinical impression is that increased

intraoperative blood loss occurs secondary to poor

hemostasis from exposed vascular beds following

excision or donor harvesting if core temperature is

less than 36°C. Hypothermia also causes postoperative shivering, which increases VO2 to 300% to

400% of normal, may cause graft shearing, and can

make the patient very uncomfortable.

To prevent intraoperative hypothermia, the patient should be covered with a space blanket while

being transported. The operating room is warmed

to 25°C to 30°C and humidified to 50% to 60%

relative humidity. All solutions for preparation of

the skin are warmed, as are all crystalloid and

colloid solutions for infusion. Anesthetic gases are

warmed and humidified. A warming blanket is

placed under the patient, all nonoperative sites are

draped, and portable warming lights are used.

Postanesthetic Considerations

Major postanesthetic considerations include the

need for a smooth emergence from anesthesia, the

decision whether to extubate, the provision of comfort in the postoperative period, and the need for

adequate physiological monitoring. A smooth emergence from anesthesia is desirable, since patient

movement causes shearing of freshly placed grafts.

Adequate pain control is necessary for this, and

extubation while the patient is deeply anesthetized,

followed by gradual emergence in the intensive

care unit or recovery room, may be appropriate in

selected patients.

Many burn patients will remain intubated postoperatively secondary to the need for continued

mechanical ventilation, continued airway protection, or pulmonary toilet. Others may be extubated,

provided that they are awake, able to follow commands, have adequate ventilation and oxygenation,

have had adequate reversal from neuromuscular

blockade, and are warm.

Transport to the recovery room should be undertaken with the precautions discussed previously.

Adequate analgesia should be afforded via intravenous narcotics. If the anesthetic was ketaminebased, a quiet recovery area and adequate reassurance may reduce the incidence of undesirable

emergence delirium.

SUMMARY

Combat casualties with burns are likely to have,

in addition, penetrating missile wounds. This fact

is a consequence of modern warfare, in which most

soldiers who sustain burn injuries are wounded

within armored fighting vehicles and are therefore

subject to injury from fragments arising from the

antiarmor warhead, in addition to the secondary

explosives that may accompany battle damage.

Thus, military anesthesia providers are frequently

faced with the problem of treating casualties with

multiple traumas, one of which is a cutaneous burn.

In addition, we must maintain heightened vigilance

for the possibility of coexisting inhalation injury in

casualties who have sustained burn injuries within

the closed confines of tanks and warships. Assuming that there is no evidence of airway compromise,

initial care of the burn casualty focuses on fluid

resuscitation. During the first 24 hours, the essential component of fluid resuscitation is the Modified Brooke Formula (ie, the intravenous infusion of

2–4 mL Ringer’s lactate/kg body weight/% TBSA

burned). The adequacy of fluid resuscitation must

be monitored frequently by observing such indicators of the normalcy of peripheral perfusion as the

urinary output.

Anesthesia may be required during several different phases of burn wound care. Casualties with

full-thickness burns of the extremities in which the

peripheral circulation is compromised, or in whom

thoracic excursion is hindered, will require escha-
Anesthesia and Perioperative Care of the Combat Casualty

538

rotomy. This procedure can usually be performed

without anesthesia. When a substantial cutaneous

burn is present (> 30% TBSA), the initial wound care

is best carried out with a narcotic-based, balanced

anesthesia using a low concentration of inhaled

vapor. Initial wound care of lesser burns can be

carried out with intravenous ketamine. Ketamine

can also be used for subsequent wound management in some casualties. Those casualties who

require general endotracheal anesthesia at 24 hours

or more after the burn injury should not receive

succinylcholine because of its recognized propensity to cause massive release of potassium and possible sudden death from hyperkalemia.

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75. Goodall MC. Sympatho-adrenal medullary response to thermal burn. Ann N Y Acad Sci. 1968;150:685–689.

76. Fozzard HA. Myocardial injury in burn shock. Ann Surg. 1961;151:113–119.

77. Schaner PJ, Brown RL, Kirksey TD, Gunther RC, Ritchey CA, Gronert GA. Succinylcholine hyperkalemia in

burned patients. Anesth Analg. 1969;48:764–770.

78. Gronert GA, Theye RA. Pathophysiology of hyperkalemia in burned patients. Anesthesiology. 1975;43:89–99.

79. Martyn JAJ, Matteo RS, Szyfelbein SK. Unprecedented resistance to neuromuscular blocking effects of metocurine

with persistence after complete recovery in a burned patient. Anesth Analg. 1982;61:614–617.

80. Martyn JAJ, Goudsouzian NG, Liu LMP, Szyfelbein SK, Kaplan RF. Metocurine requirements and plasma

concentration in burned pediatric patients. Br J Anaesth. 1983;55:263–268.

81. Martyn JAJ, Liu LMP, Szyfelbein SK, Ambalavanar ES, Goudsouzian NG. Neuromuscular effects of pancuronium

in burned children. Anesthesiology. 1983;59:561–564.

82. Yamashita M, Shiga T, Matsuki A. Unusual resistance to pancuronium in severely burned patients: Case reports.

Can Anaesth Soc J. 1982;29:630–631.

83. Sarubin J. Increased requirement of alcuronium in burned patients. Anesthetist. 1982;31:392–395.
Anesthesia and Perioperative Care of the Combat Casualty

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84. Martyn JAJ, Szyfelbein SK, Ali HH. Increased d-Tubocurarine requirement following major thermal injury.

Anesthesiology. 1980;52:352–355.

85. Martyn JAJ, Greenblatt DJ, Lebowitz PW, Savarese JJ. Pharmacokinetics of d-Tubocurarine in patients with

thermal injury. Anesth Analg. 1982;61:241–246.

86. Dwersteg JF, Pavlin EG, Heimbach D. Burn patients are resistant to atracurium. Anesthesiology. 1985;63:A338.

Abstract.

87. Mills A, Martyn JAJ, Szyfelbein SK. Evaluation of atracurium neuromuscular blockade in burned children.

Anesthesiology. 1985;63:A339. Abstract.

88. Owen RT. Resistance to competitive neuromuscular blocking agents in burn patients: A review. Methods Find

Exp Clin Pharmacol. 1985;7:203–207.

89. Pavlin EG. Perioperative fluid requirements in the thermally injured patient. In: Martyn JAJ, ed. Acute

Management of the Burned Patient. Philadelphia, Pa: WB Saunders; 1990: 231–238.

90. Pavlin EG, Strakeljahn C. Operating room considerations in care of the burn patient. In: Boswick JA, ed. The Art

and Science of Burn Care. Rockville, Md: Aspen Publishers; 1987: 82–91.

91. Martyn JAJ, Szyfelbein SK. Anesthetic management of the burned patient. In: Martyn JAJ, ed. Acute Management

of the Burned Patient. Philadelphia, Pa: WB Saunders; 1990: 217–230.

92. Pavlin EG, Yazaki S, Heimbach DM. The effects of ketamine and neurolept anesthesia on oxygen consumption

(VO2) and cardiac output in the hypermetabolic burned patient. Anesthesiol. 1981;56(suppl):A190. Abstract.

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Metabolic Derangements and Nutritional Support

543

DOUGLAS N. WHATMORE, M.D.*

Chapter 23

METABOLIC DERANGEMENTS AND

NUTRITIONAL SUPPORT

INTRODUCTION

METABOLIC DERANGEMENTS IN COMBAT CASUALTIES

Starvation

Exercise

Starvation, Exercise, and Stress

The Effect of Injury

Stages in the Response to Stress

Energy Requirements of Patients With Injuries or Infections

NUTRITIONAL SUPPORT

Nutritional Assessment

Parenteral Nutrition

Enteral Nutrition

Assessment of Nutritional Repletion

SUMMARY

INFECTION CONTROL POLICY AND PROCEDURE GUIDE

*Lieutenant Colonel, Medical Corps, U.S. Army (ret); formerly, Chief, Critical Care Medicine Service, Walter Reed Army Medical Center,

Washington, D. C. 20307-5001, and Consultant in Critical Care Medicine to The Surgeon General, U.S. Army; currently, private practice of

critical care medicine, 2860 Channing Way, Suite 214, Idaho Falls, Idaho 83404
Anesthesia and Perioperative Care of the Combat Casualty

544

INTRODUCTION

A detailed review of the biochemistry of normal

metabolism is beyond the scope of this chapter but

a brief review of the more fundamental processes is

not inappropriate. Greater emphasis will be placed

on recording the gross perversions of normal metabolism that occur during life-threatening trauma—

especially when accompanied by sepsis. The remainder of the chapter will describe practical aspects

of the nutritional interventions at the disposal of

military critical care specialists.

The energy to drive all cellular processes is stored

in high-energy phosphate compounds, either adenosine 5 ́-triphosphate (ATP) or phosphocreatine.

These are generated by (a) glycolysis, which occurs

within the Embden-Meyerhof pathway, and (b) oxidative phosphorylation, which takes place in the

tricarboxylic acid (TCA) cycle in conjunction with

the proteins that constitute the respiratory chain. In

glycolysis, glucose is broken down into pyruvate or

lactate, while the TCA cycle produces carbon dioxide and metabolic intermediates that carry electrons and protons to the chain of respiratory proteins located in the inner membrane of the mitochondria (Figure 23-1). In contrast to glycolysis, in

which the enzymatic machinery is found distributed throughout the cytoplasm of cells and can

function without oxygen, the complete complement

of enzymes needed for the TCA cycle is found

exclusively within mitochondria and functions only

in the presence of oxygen. As the electrons are

passed along the respiratory chain, protons are

driven into the space between the inner and outer

membranes of the mitochondria, resulting in the

development of a proton gradient across the inner

membrane. Under the influence of the gradient,

protons flow back through the inner membrane,

passing through specialized proteins that generate

ATP. The electrons combine with oxygen and protons to form water. Oxidative phosphorylation

produces the vast majority of the body’s metabolic

energy: in the presence of oxygen, 1 molecule of

glucose can be made to generate as many as 38

Fig. 23-1. The chemiosmotic theory, illustrated here, is the accepted explanation of how oxidative phosphorylation

produces high-energy phosphate compounds. The schematic shows a portion of the wall of a mitochondrium. A

characteristic feature of this organelle is a wall formed by an outer and an inner membrane that are separated by a

space. The cytochrome oxidation-reduction proteins are located in the inner membrane. The tricarboxylic acid (TCA)

cycle produces protons (H+), which are extruded through the inner membrane, and electrons (e–), which are passed

along the cytochrome system until they react with oxygen. The protons, which have collected in the space between the

membranes, ultimately pass back into the interior of the mitochondrium through specialized proteins embedded in the

inner membrane. Here they cause adenosine 5 ́-triphosphate (ATP) to form from adenosine diphosphate (ADP) and

inorganic phosphate. The protons subsequently react with oxygen to form water.

Electron-Transfer Proteins

TCA

Cycle

e–

H+

ADP ATP

H+ H+

Inner Membrane

Outer Membrane
Metabolic Derangements and Nutritional Support

545

Tricarboxylic

 Acid Cycle

Fig. 23-2. The interrelation of the principal classes of metabolites that serve as the source of energy for human activity:

carbohydrates, fats, and proteins. The central process is that of the tricarboxylic acid (TCA) cycle, entrance into which

is by means of acetylcoenzyme A (acetyl-CoA). The latter substance is made from pyruvate, which comes from the

metabolism of carbohydrates and certain amino acids, and from coenzyme A esters formed from fats. Most of the

reactions shown are reversible (double-ended arrows) except for the one linking pyruvate and acetyl-CoA. This fact

has important implications for understanding the metabolic derangements that occur during severe trauma. Although

carbohydrates can be converted into fats, fats cannot be converted directly into carbohydrates. When the supply of

carbohydrates to individual cells is inhibited, such as during starvation and when insulin resistance exists, fat

catabolism is accelerated to supply acetyl-CoA for use by the TCA cycle. However, an alternative source of glucose is

needed to meet the needs of organs that use glucose as the obligatory substrate. The glucose cannot be obtained from

fat because the the pyruvate–acetyl-CoA reaction is irreversible. The needed glucose is obtained by a process in which

alanine is converted into pyruvate. There will also be accelerated entry of amino acids such as aspartate and glutamate

into the TCA cycle. In this metabolic state, which is commonly seen following severe trauma, the amino acids needed

to form glucose are obtained from the catabolism of protein—but not from fat because of the irreversibility of the

pyruvate–acetyl-CoA reaction.

Citrate

Malate Aconitate

Fumarate Isocitrate

Succinate α-Ketoglutarate Glutamate

Proteins

Hexoses

Glycogen

Phosphorylated Hexose Coenzyme A Esters α-Keto Acids

Pentose

Phosphorylated Trioses Pyruvate

Ketone Bodies

Pyruvate

Lactate

Alanine

Asparate

Carbohydrates Fats

Glycerol Fatty Acids Amino Acids

Acetylcoenzyme A

Oxaloacetate

molecules of ATP. By way of contrast, the metabolism of 1 molecule of glucose in the absence of

oxygen produces only 2 molecules of ATP.1

The ultimate metabolic precursors of high-energy phosphate compounds are complex carbohydrates, which are, for the most part, polymers of sixcarbon molecules known as hexoses; fats, which

are glycerol–fatty acid esters; and proteins, which

are polymers of amino acids (Figure 23-2). The

initial steps leading to the formation of ATP involve

the breaking down of the complex carbohydrate,

fat, and protein molecules into their constituents,

which then form the substrates for oxidative phosphorylation. Hexoses, of which glucose is the most

important, are converted to pyruvate, which, depending on the availability of oxygen, is converted

either to lactate or to acetylcoenzyme A (acetylCoA). Fatty acids as well as the nitrogen-free residue of amino acids also form acetyl-CoA. AcetylCoA is the point of entrance into the TCA cycle,

where metabolic intermediates derived from carbohydrates, fats, and proteins interact. Amino acids

derived from protein in skeletal muscles can be

converted to glucose, and excessive dietary inges-
Anesthesia and Perioperative Care of the Combat Casualty

546

Energy Stores

tion of glucose can lead to the formation of fatty

acids, which are then stored as fat in adipose tissue.

Fat, however, cannot be converted directly to glucose unless the constituent fatty acids either contain

an odd number of carbon atoms or have branching

chains.

Glucose is the most immediately available energy source and the one in highest demand by the

body. A number of tissues, the central nervous

system particularly, are obligate glucose users and

must have a continuous supply. Fibroblasts and

formed elements of the blood such as erythrocytes,

as well as the renal medulla, all depend on glucose.

Six hundred to 1,000 kcal/d must be provided to

these tissues, and glucose is preferentially made

available even if the rest of the body must shift to

another energy source such as lipid. However,

glucose reserves are sharply limited and consist

of about 20 g within the body at any given time.

More important are the 300 to 400 g glycogen (a

polymer of glucose) that are stored in the liver and

skeletal muscle. Although the synthesis of glycogen from glucose is easily reversed by the process of

glycogenolysis, glycogen is not an optimally efficient storage medium because both its formation

and its degradation require the expenditure of energy. In fact, when the synthesis of glycogen stems

from noncarbohydrate sources, instead of the usual

3.4 kcal/g obtained from the oxidation of glucose to

water and carbon dioxide, a net increase of as little

as 1 to 2 kcal additional energy may be produced by

the complete oxidation of 1 g of glycogen.

The availability and utilization of carbohydrate

are controlled by a complex interplay of hormones,

with insulin and glucagon the major factors. Insulin is an anabolic hormone; it reduces plasma glucose levels by (a) increasing glucose transport into

cells, whereby glycolysis is stimulated, and (b) increasing glycogen synthesis in liver and muscle.

Insulin also blocks gluconeogenesis (wherein amino

acids derived from the catabolism of body proteins

are converted into glucose) and promotes protein

synthesis. Glucagon counters these effects of insulin by promoting glycogenolysis and gluconeogenesis in the liver and lipolysis in the adipose stores.

(The latter effect is opposite of that of insulin, which

causes fat synthesis.) The ratio of insulin to glucagon controls the balance and is a major determinant

of the ability to mobilize energy stores. A high ratio

defines an anabolic state (ie, more-complex molecules are synthesized from simpler molecules); a

low ratio, a catabolic state (ie, complex molecules are

degraded to simpler molecules).

As previously indicated, the body has the biochemical machinery to use triglycerides and proteins for oxidative phosphorylation once glucose

and glycogen reserves are used up (see Figure 23-2).

The relative importance of the body’s reserves of

carbohydrates, fat, and protein as sources of energy

is shown in Table 23-1. At any given time, the actual

contribution of the carbohydrates, fats, and proteins to overall energy production can be estimated

by measuring the respiratory quotient (RQ), which

is discussed in Exhibit 23-1 and in greater detail

later in this chapter.

Lipids are the most abundant, although not the

most readily available, energy source. The average

70-kg soldier has 100,000 kcal stored as lipid (9

kcal/g),2 and this reserve becomes the principal

fuel source during starvation. Fats are broken down

into their constituent fatty acids and glycerol, a

process known as lipolysis. Two types of lipases

act to convert stored lipid to the more readily

available fuels glycerol and fatty acid. Hormonesensitive lipase (activated by adenosine 3 ́,5 ́-cyclic

monophosphate [cAMP], which, in turn, is triggered by catecholamine receptors on the adipocyte

membrane) degrades lipids to fatty acids and glycerol. The fatty acids enter the TCA cycle as acetylCoA, and the glycerol is either transformed to pyruvate or esterified to triglyceride in the liver. The

second lipase, lipoprotein lipase, catalyzes the release of triglycerides from low-density lipoproteins

and chylomicrons, an effect that is inhibited by catecholamines. The presence of glucose and insulin

tends to enhance the effects of lipoprotein lipase.

TABLE 23-1

ENERGY STORES IN A 70-KG MAN

Energy Source Tissue (g) (kcal)

Triglycerides Fat 15,000 100,000

Protein Muscle 6,000 25,000

Glycogen Liver 70 280

Muscle 120 480

Glucose Throughout body 20 80

Adapted with permission from Linder MC. Energy metabolism,

intake, and expenditure. In: Linder MC, ed. Nutritional Biochemistry and Metabolism with Clinical Applications. New York, NY:

Elsevier; 1985: 290.
Metabolic Derangements and Nutritional Support

547

EXHIBIT 23-1

METABOLIC TERMINOLOGY

Respiratory Quotient (RQ): The molar ratio of CO2 produced for O2 consumed, or VCO2/VO2. For

carbohydrates, this is 1.0 (ie, one mole of CO2 is generated for each

mole of O2 consumed). For the oxidation of fats, the ratio is 0.7; for

protein, 0.82. The conversion of carbohydrate to fat (ie, lipogenesis) can

theoretically have an RQ > 8.0. Whenever the respiratory quotient is

> 1.0, lipogenesis (and therefore overfeeding) is occurring. Remember

that changes in the respiratory quotient directly affect PO2 and PCO2.

Alveolar PO2 will fall with a decreasing RQ, for any given level of PCO2.

PCO2 will rise with an increasing RQ, and will require a higher minute

ventilation to normalize.

O2 Consumption (VO2): The amount of oxygen consumed by metabolic processes in 1 min,

given as

Minute Ventilation (L/min) • (FIO2 – FEO2)

when the RQ is 1.0.

CO2 Production (VCO2): The amount of CO2 generated by metabolic processes in 1 min, given as

Minute Ventilation (L/min) • FECO2

O2 Delivery (DO2): The amount of O2 carried to the tissues each minute, calculated as

C.O. (L/min) • CaO2, or

C.O. • [(1.39 • SaO2 • Hb) + (0.003 • PO2)]

DO2 is given in mL/kg/min; about 16 mL/kg/min is normal for

adults. Normal VO2 is about 4 mL/kg/min.

O2 Extraction Ratio (OER) The percentage of the delivered O2 actually consumed in metabolic

processes, or VO2/DO2. This is about 25% in normal adults, and

normally decreases as O2 delivery increases.

Resting Energy Expenditure (REE): The energy expenditure measured at rest or lying down. REE can be

calculated from VO2, VCO2, and a measurement of metabolized nitrogen (eg, Nu, nitrogen excreted in the urine)*:

REE (in kcal/min) = 3.581 (kcal/L) • VO2 (in L/min)

+ 1.448 (kcal/L) • VCO2 (in L/min) – 1.773 (kcal/g) • Nu (in g/min)

*REE may be normalized for body surface area or mass by dividing by area in square meters, or mass in kilograms,

respectively. Since the contribution of the term 1.773 Nu is small, Bursztein has calculated that a 100% error in measured Nu

will be associated with only a 1% error in REE. Therefore, from the practical standpoint, the last term in the REE equation can

be ignored, since determination of nitrogen excretion is not necessary to estimate energy expenditure. Source for REE

definition and equation: Bursztein S, Elwyn DH, Askanazi J, Kinney JM. Energy Metabolism, Indirect Calorimetry, and Nutrition.

Baltimore, Md: Williams & Wilkins; 1989: 30, 59, 62.

CaO2: arterial oxygen contents; C.O.: cardiac output; FEO2: fraction of expired oxygen; FIO2: fraction of inspired oxygen; Hb:

hemoglobin; PCO2: partial pressure of carbon dioxide; PO2: partial pressure of oxygen; SaO2: oxygen saturation of arterial

blood

Insulin inhibits lipolysis; in fact, a high ratio of

insulin to glucagon will promote storage of fuel as

lipid. Catecholamines, glucagon, and somatotropin (ie, growth hormone) all promote the breakdown of the lipid stores for energy. Steroids will

enhance the lipolytic effects of catecholamines and

glucagon.

An additional option that the body has to supply

glucose or substrates for oxidative phosphorylation

is to utilize amino acids, from either ingested or

structural proteins, as fuel. There are five points

where the carbon skeletons of amino acids can enter

the glucose oxidation pathway: as pyruvate, acetylCoA, α-ketoglutarate, fumarate, and succinylco-
Anesthesia and Perioperative Care of the Combat Casualty

548

enzyme A (succinyl-CoA). Protein may be diverted

for use as a fuel source, normally as excess dietary

protein, or as catabolized structural protein in stress

states. Protein yields 4.1 kcal/g.

Normal protein turnover—breakdown and synthesis—is approximately 300 g/d.3,4 Normal daily

protein turnover in skeletal muscle is 100 g/d.

Roughly 50 g, which is used to produce digestive

juices, and another 20 g of small intestinal lining

cells are lost daily in digestion. Eighty to one

hundred grams of protein is ingested daily in a

typical Western diet. Excess is converted to fuel,

and the nitrogen is excreted as urea. Enzymes are

continually made, used, and broken down; structural proteins are continually modified; and cells

are continually replaced. In normal adults, 15% to

20% of the basal metabolic rate (BMR) is due to

metabolism of protein.

Amino acids are transported by a membrane

carrier system,3,4 often against a steep concentration

gradient (as opposed to the glucose carrier system).

There are seven carriers, specific for different amino

acids but with some overlap. Amino acids are

constantly being cycled into and out of the cells and

transaminated or deaminated for use in cellular

processes. Different processes feed these substrates

into the cellular plants—hydrolysis of dietary (or

structural, in starvation) protein, amination of keto

acids, conversion of amino acids and ketoacids to

other compounds, use of amino acids for protein

synthesis, oxidation of ketoacids—to balance the

supply of amino acids with the demand. Most

processes involve transamination to glutamate as

the common path for transfer.

Metabolism of carbohydrates, fats, and proteins is regulated by a complex neural and hormonal feedback system. The hypothalamus controls both the normal function of the system and the

response of the organism to starvation and stress.

Stimulation of the ventromedial hypothalamic nucleus by concentrations of metabolic substrates (eg, carbohydrate, lipid, and amino acids),

along with input from aortic baroreceptors, renal

nerves, and the carotid sinuses, as well as changes

in the concentration of hormones are all feedback

elements that guide the orchestration of the system

by the hypothalamus. When the nucleus is stimulated, sympathetic and parasympathetic outflow

increase. The adrenal medulla is stimulated via

the great splanchnic nerve. This increase in sympathetic outflow mobilizes substrate (from glycogen stores, lipid pools, and skeletal muscle), increases cardiac output and minute ventilation, and

releases insulin and glucagon from the pancreas.

Parasympathetic outflow increases absorption of

nutrients by the gut. Pituitary hormones—adrenocorticotropic hormone (ACTH), somatotropic

hormone (STH), thyroid-stimulating hormone

(TSH), prolactin (PRL), luteinizing hormone (LH)

and follicle-stimulating hormone (FSH) from the

anterior pituitary, and antidiuretic hormone (ADH)

from the posterior pituitary—control utilization of

substrate and fluid balance and osmolarity. Insulin

is stimulated by the release of β-adrenergic catecholamines, while glucagon is stimulated and insulin is inhibited by α-adrenergic catecholamines

and increased adrenal hormones. Portal blood levels of both insulin and glucagon are significantly

higher than systemic levels, as is their utilization by

the liver. The ratio of insulin to glucagon concentration dictates whether the response is anabolic or

catabolic.

The mobilization of free fatty acids is controlled

by an interplay among ACTH, corticosteroids, catecholamines, and glucagon. ACTH also controls

the secretion of beta endorphin and melanocytestimulating hormone (MSH). This corticotrophinreleasing hormone (CRH)–ACTH–cortisol axis plays

a crucial role in our ability to respond to a stressful

stimulus. The patterns of response are nearly uniform; only the degrees differ.

The critical importance of the relative ratio of

insulin to glucagon cannot be overemphasized. The

ratio is one of the chief determinants of catabolism

versus anabolism and is responsible for maintaining normal glucose levels in all tissues, particularly

the obligate glucose users. Depletion of glycogen stores triggers a shift in the ratio: a fall in

insulin levels and an increase in glucagon. The liver

responds to this change by increasing gluconeogenesis: amino acids from skeletal muscle protein are

stripped of their carbon skeleton to make more

glucose. Glucagon activates catecholamine-sensitive lipase in adipose tissues; triglycerides are broken down and the circulating free fatty acids and

glycerol are fed to the liver, which catabolizes them

to ketones to be used as an oxidative fuel source.

When the ratio is reversed, carbohydrate is converted to glycogen and fat for storage of chemical

energy, and protein synthesis is stimulated.

Before we move on to specific metabolic derangements and nutritional support, the reader

should review the metabolic terms and their descriptions in Exhibit 23-1.
Metabolic Derangements and Nutritional Support

549

METABOLIC DERANGEMENTS IN COMBAT CASUALTIES

Most patients seen by medical officers in field

medical facilities will be members of the armed

forces: young, well developed, predominantly male,

and with no significant medical history. The typical

soldier in the U.S. Army will have entered the

combat zone with a large muscle mass and greaterthan-normal glycogen stores, but many factors are

likely to modify the picture of this healthy, muscular soldier. Of these factors, the most important are

starvation, exercise and stress and, in the event of a

combat injury, the wound itself. Major W. J. Phillips,

Medical Corps, U.S. Army, has published an excellent introduction to this subject.5

Starvation

How does starvation affect metabolism? Glucose is no longer available either from glycogen or

from externally supplied carbohydrates, yet several organs such as the brain will not tolerate an

interruption in their supply of glucose. After only 8

hours without intake, the body begins to use its glycogen reserves to support the obligate glucose-utilizing

tissues—the central nervous system, renal medulla,

formed blood elements, and fibroblasts—while the

metabolic economy shifts to fatty acid oxidation. Even

though energy expenditure may be minimized by a

decrease in resting energy expenditure (REE, which is

discussed later in this chapter), the available glycogen

stores will be depleted within 24 hours. A starved,

stressed patient will rapidly catabolize nonvital

structural proteins to fuel metabolic processes.

The initial adjustment to an inadequate intake of

nutrients is to form glucose from amino acids derived from skeletal muscle protein. Branched-chain

amino acids are transaminated to alanine and

glutamine, which are “stripped” in the liver for

their carbon skeletons to make glucose, or they are

used as intermediates in the TCA cycle. A starved

patient loses roughly 75 g of muscle protein, or 200

to 300 g of structural muscle tissue, each day. The

urea and ammonia generated by this process are

excreted by the kidney. The energy for gluconeogenesis comes from catabolism of fatty acids supplied by the lipolysis of adipose tissues.3,6,7

Within 1 week, metabolism of fatty acids becomes the principal source of fuel to meet the body’s

needs. The activation of catechol-sensitive lipase in

adipose tissue causes the release of free fatty acids

and glycerol. Glycerol is converted to glucose or to

pyruvate, which enters the TCA cycle. A consequence of the accelerated metabolism of fatty acids

during starvation is the production of ketone bodies and their increasing use by organs such as the

heart and brain in place of glucose. The adaptation

of the heart and brain to utilize ketone bodies is of

critical importance in prolonging survival during

starvation, since it allows for a marked reduction in

the glucose needs of the body (perhaps 5% of normal) that otherwise could not be meet by gluconeogenesis beyond about 2 weeks (Figure 23-3).

Fats become the primary fuel, with the utilization of lipid becoming a major adaptive response,

conserving protein. Protein catabolism declines as

the body’s energy needs are increasingly met by

catabolism of fat. As simple starvation continues,

the rate of catabolism decreases from roughly 300 g

of muscle tissue per day to 150 g/d. In simple

starvation, the intake of carbohydrate can spare

protein to some extent. How are these responses to

starvation brought about? The fall in glucose causes

a fall in insulin, with a consequent, although lesser,

inhibition of lipolysis. Glucagon rises as insulin falls,

accelerating both lipolysis and glycogenolysis.

What are the systemic medical effects of starvation

for a significant period (ie, longer than several days)?

All organs are affected by the loss of structural, and

often of functional, proteins. The lungs lose the ability

to clear bacteria, connective tissues degenerate, and

emphysematous changes are the result. Respiratory muscles atrophy. The heart dilates, and, after

a time, focal necrosis and fibrosis appears, with

myofibrillar degeneration. Red and white blood

cell counts fall with decreased production of erythropoietin (ie, erythropoietic hormone) and stem cells.

The gut, which has more rapidly dividing cells than

any other organ, loses mass out of all proportion to its

size as it atrophies. The liver and kidneys lose mass,

and the liver begins to accumulate fat. The immune

system becomes less and less able to respond to infection, as the number of T helper cells declines and

polymorphonucleocytes lose their chemotactic abilities. If hypermetabolism is added to simple starvation, then the catabolism of protein predominates,

and the changes discussed are far more profound.

Exercise

The metabolic consequences of exercise depend

on both the duration and the intensity of the exer-
Anesthesia and Perioperative Care of the Combat Casualty

550

Origin of blood

glucose

Tissues using

glucose

Major fuel of

the brain

V

Gluconeogenesis,

hepatic and renal

Brain at a diminished

rate, red blood cells,

renal medulla

Ketone bodies, glucose

I

Exogenous

All

Glucose

II

Glycogen

Hepatic

gluconeogenesis

All except liver

Muscle and adipose

tissue at diminished

rates

Glucose

III

Hepatic

gluconeogenesis

Glycogen

All except liver

Muscle and adipose

tissue at rates

intermediate

between II and IV

Glucose

IV

Gluconeogenesis,

hepatic and renal

Brain, red blood cells,

renal medulla; small

amount by muscle

Glucose, ketone

bodies

Fig. 23-3. The amount of glucose consumed and its source depend on the phase of alimentation. In the immediate

postabsorptive phase, exogenous glucose forms the major source and is consumed by all tissues (I). Within 3 to 4 hours

of eating, glycolysis of liver glycogen is the major source of glucose (II). The major source of glucose after 24 hours is

gluconeogenesis from amino acids released by the catabolism of skeletal muscle protein (III). When fasting progresses

to starvation, glucose consumption is increasingly restricted to red blood cells and the renal medulla (IV). During

starvation, glucose consumption by the brain progressively falls, as the brain increasingly uses ketone bodies as its

major source of energy (V). Whatever glucose is produced comes from gluconeogenesis. Reprinted with permission

from Linder MC. Energy metabolism, intake, and expenditure. In: Linder MC, ed. Nutritional Biochemistry and

Metabolism with Clinical Applications. New York, NY: Elsevier; 1985: 291.

The Five Phases of Glucose Homeostasis

cise. The most intense exercise (eg, running at

maximum speed carrying full combat gear) causes

muscle ATP and phosphocreatine to be totally consumed in less than 1 minute. If the exertion, albeit

at a reduced rate, is prolonged beyond 10 seconds,

muscle glycogen stores begin to be broken down to

glucose, which, in turn, is metabolized to lactic acid.

Anaerobic metabolic pathways—and especially the

breakdown of muscle glycogen—are the primary

energy source for maximum-intensity exercise that

lasts less than several minutes. The amount of

glycogen available in muscle is the major metabolic

determinant of performance during short, highintensity exertion. In normal circumstances, about

80% of the lactic acid formed during anaerobic

exercise is converted rapidly back to glucose; the

remainder enters the TCA cycle where it will be

metabolized to carbon dioxide.

Only when the duration of high-intensity exercise exceeds 3 or 4 minutes does aerobic metabolism

become the predominant source of high-energy

phosphates. During prolonged exercise under aerobic conditions, the initial major source of energy is

liver glycogen, followed by fatty acids. Neverthe-
Metabolic Derangements and Nutritional Support

551

Fig. 23-4. Restoration of muscle glycogen levels after

vigorous exercise very much depends on the consumption of a diet high in carbohydrates. A similar degree of

glycogen repletion will not occur when most of the calories are provided by a diet rich in fats and proteins.

Reprinted with permission from Fox EL. Sports Physiology. Philadelphia, Pa: WB Saunders; 1979: 69.

less, glycogen depletion occurs with long-distance

running or prolonged marching with a full combat

load, even given the steady-state conditions of aerobic energy production. Reconstitution of depleted

glycogen becomes an important determinant of further exercise performance. Restoring muscle and

liver glycogen stores to normal greatly depends on

the types of food consumed after the exercise (Figure 23-4). Thus, the combination of prolonged

exercise and nutritional deprivation may seriously

degrade exercise performance.

Starvation, Exercise, and Stress

Starvation is simply the lack of nutrient intake.

Few inflammatory mediators are released, and the

body responds to exogenous replacement. But now

we add moderate stress in the forms of sleep deprivation, anxiety or even fear, cold or heat, and arduous physical exertion—a combination especially

likely to occur during military operations. Starvation puts humans into glycogenolytic and gluconeogenetic metabolic modes, the latter being ultimately suppressed by the development of lipolysis

and the formation of ketone bodies. Unfortunately,

exercise and stress interfere with this adaptation.

Stress increases glucose utilization out of proportion to total energy expenditure, while it also increases energy expenditure. Glycogen stores are

depleted more rapidly. Increased levels of glucagon, catecholamines, and cortisol—hormones that

characterize the human response to stress—accentuate gluconeogenesis. Fat is no longer the primary

energy source; the body utilizes protein stores instead. Each day, 250 g of fat and 3- to 4-fold that

amount of muscle tissue are catabolized to produce

new glucose.

Actual measurements of these derangements

during combat operations are next to impossible to

make for obvious reasons. Fortunately, however,

the U.S. Army Research Institute of Environmental

Medicine (USARIEM) has studied the effects of

starvation, exercise, and stress during the U.S.

Army’s Ranger Training Course.8 This is the training exercise that most closely mimics real combat.

The training course is extremely arduous; typically,

only 40% to 50% of its students pass. The course

lasts 62 days and is carried out in four phases in

geographically and climatically diverse settings: at

Fort Benning, Georgia, and in mountain, jungle,

and desert environments in Georgia and elsewhere

in the United States.

In the USARIEM study, which was published in

1992, the mean weight loss of Rangers in training

over the 62-day course was 12.1 ± 3.4 kg (range 6.5–

20.6 kg), which corresponded to a median weight

loss of 15.6% of initial body weight. Body fat fell

from about 15% of body weight at the beginning of

the training to about 6% at the end. Fat-free mass

(an index of muscle tissue) fell an average of 4.6 kg.

These reductions in body mass were clearly due to

the marked imbalance between total body energy

expenditure (which averaged 4,010 ± 830 kcal/d)

and estimated food energy intake (which averaged

3,930 ± 290 kcal/d) (Figure 23-5). Peak energy

expenditures during the mountain phase were estimated to exceed 6,000 kcal/d. By way of contrast,

an average, unstressed man requires about 2,000

kcal/d, and an unstressed woman about 1,800 kcal/d.

The combination of inadequate caloric intake,

stress, and exercise caused profound endocrine disturbances (Figure 23-6). As expected, the level of

insulin and insulinlike growth factor (IGF-1) showed

significant decreases, which suggest the magnitude

of the ongoing protein catabolism. The cortisol

level increased and although glucagon was not

measured, we may assume that it also increased

since glucagon’s role, like cortisol’s, is to mobilize

the body’s noncarbohydrate energy reserves. Not

shown on the graph, but of considerable interest, is

the nearly 1,000% increase in growth hormone (ie,

somatotrophin). The homeostatic importance of
Anesthesia and Perioperative Care of the Combat Casualty

552

Fig. 23-5. Energy balance during the

2 months of the U.S. Army Ranger

training course. Solid lines represent

estimated energy expenditure, while

broken lines represent estimated energy intake. Except for the brief periods of transition between the training

phases, the Rangers ate fewer calories

than they expended. Reprinted from

Moore RJ, Friedl KE, Kramer TR,

et al. Changes in Soldier Nutritional

Status and Immune Function During

the Ranger Training Course. Natick,

Mass: US Army Research Institute of

Environmental Medicine; 1992: 51.

USARIEM Report T13-92.

Fig. 23-6. Measured changes in the

levels of various hormones during

the 62-day U.S. Army Ranger training course. Data are given as percentages of the baseline values. The elevation of cortisol and the depression

of insulin are consistent with stress

and starvation. The actual concentration of testosterone approached the

level found in castrated men. However, the cause in the Rangers is not

testicular dysfunction but rather a

profound suppression of the elaboration of pituitary gonadotropin. Data

source: Moore RJ, Friedl KE, Kramer

TR, et al. Changes in Soldier Nutritional Status and Immune Function

During the Ranger Training Course.

Natick, Mass: US Army Research Institute of Environmental Medicine;

1992: Table 23, p 68. USARIEM Technical Report T13-92.

this alteration is unclear, since growth hormone has

anabolic effects and, in fact, is increasingly used for

that purpose in nutritionally depleted catabolic surgical patients.9

Other consequences of the combined starvation,

exercise, and stress that characterize the Ranger

Training Course, and military operations in general, are loss of strength in large muscle masses such

as the thighs (no doubt due to the generalized loss

of lean body mass) and dramatic evidence of a loss

of cell-mediated immune function. Such indices of

T lymphocyte function as phytohemagglutininstimulated proliferation and interleukin-2 (IL-2)

production were reduced by one half. Production

of IL-6 fell to a similar extent. These derangements

are clinically relevant: 50% of the population studied were treated with antibiotics for infection. The

cumulative effects of starvation, exercise, and stress

can have tragic, unintended consequences. On 15

February 1995, four Ranger students at Fort Benning

died from hypothermia after a water-immersion

portion of their training. Ironically, the official

recommendations that had been prepared on the

basis of the USARIEM study had emphasized that

Time (d)

Food Intake (kcal/d) ( )

Percentage of Baseline120

100

80

60

40

160

140

20

Baseline Ft. Benning Mountain Jungle Desert

Training Phases

Cortisol

Testosterone

Insulin

Triiodothyronine

IGF-1

Energy Expenditure (kcal/d) ( )
Metabolic Derangements and Nutritional Support

553

the normal thermogenic response to mild cold is

impaired during massive weight loss.

Given the extreme psychological and physical

stresses and the less-than-ideal circumstances for

eating and resting associated with prolonged exposure to combat—or even just living in the combat

zone—the metabolic, endocrine, and immune derangements found in USARIEM’s Ranger study are

to be expected. The importance of weight loss in

soldiers should not be underestimated. The extensive slide collection of the Wound Data Munition

Effectiveness Team (WDMET) database that was

compiled during the Vietnam War contains few

photographs of combat casualties who show either

significant obesity or who have a muscular

mesomorph body habitus. Many of the soldiers

portrayed in the WDMET database appear to be

significantly malnourished (Figure 23-7).10 Medical

officers must expect to treat soldiers who are not in

optimal nutritional status when wounded. Furthermore, in every war in which the United States has

been a combatant, U.S. forces have cared for children, the elderly, and prisoners of war. This must

be kept in mind when nutritional support is planned,

because such potential casualties are likely to manifest some degree of starvation.

The Effect of Injury

When even a peripheral injury of an arm or leg is

added to starvation, mediators are released, catecholamines levels increase further, thyroid hormone is elevated, and cardiac output, oxygen delivery, and oxygen extraction all increase. If the injured

soldier is not resuscitated adequately, oxygen delivery may fall and anaerobic metabolism be initiated. Further inflammatory mediators will be released. Should the wound be of the trunk, the

Fig. 23-7. Five months after he arrived in Vietnam, this soldier was

killed by a bullet that transected his

upper spinal cord. His degree of malnutrition was not unusual. Photograph: Wound Data and Munitions

Effectiveness Team slide collection.

metabolic stresses would be the same, but with this

larger body compartment will come more tissue

damage; greater blood loss; higher levels of inflammatory mediators; and greater risks of inadequate

resuscitation, infection, and organ failure.11–13

The chain of metabolic events set in motion by

injury is complex. Not only are there direct effects

of the injury on tissue, but the body responds with

a cascade of direct effects (the immediate response

to the injury, including the steps the body takes to

protect itself from further injury) and indirect effects (those effects on metabolism resulting from

the injury and the direct effects the injury sets in

motion).

The body’s immediate responses to an injury are

(a) the activation of the sympathetic nervous system

and (b) a secondary discharge of catecholamines

from the adrenal medulla. Cardiac output, and thus

the delivery of oxygen to the tissues, increases, and

the oxygen extraction ratio also rises as tissue metabolism increases. The release of thyroid hormones, in response to the catecholamine surge, is

responsible for 50% to 60% of this increase in metabolism. As the rate of biochemical reactions increases, the core body temperature increases—but

owing to homeothermic compensatory changes, not

to the extent predicted by the inverse of van’t

Hoff’s law (ie, a reaction rate increases 7.2% for each

1°F rise in temperature). The extent to which the

temperature rises is proportional to the severity of

the illness.13,14 An increase in motor activity, whether

due to running, shivering, thrashing secondary to

pain, seizures, and so forth, usually accompanies

these responses and further increases both metabolism and temperature.

The indirect effects of stress and injury on the

body are more subtle but play as great a role in

altering metabolism. Stress acutely suppresses
Anesthesia and Perioperative Care of the Combat Casualty

554

pyruvate dehydrogenase, decreasing the amount of

pyruvate available for formation of acetyl-CoA,

and eventually of ATP. Glycogen stores are depleted quickly. Oxidation and phosphorylation

may uncouple, resulting in a markedly less-efficient metabolism. ATP production decreases, but

the production of heat rises as the efficiency of

the TCA cycle decreases. Futile cycling of substrate

via the Cori cycle occurs; at the site of the injury,

glucose is metabolized to lactate, which is then

transported back to the liver, where it is converted

back to glucose. This process produces heat but

no net gain of ATP. Oxygen consumption increases,

and the body appears to enter a state of hypermetabolism.13,14

The release of the counterregulatory hormones—

glucagon, cortisol, and ACTH—further promotes

the situation. Cortisol increases gluconeogenesis to

6- to 10-fold higher than the baseline. Peripheral

proteins are catabolized, and the amino acids are

taken up by the liver. Free fatty acids are mobilized

from lipid pools and transported to the liver, where

glucagon stimulates the use of the carbon skeletons

of amino and fatty acids for gluconeogenesis. Release of inflammatory mediators, such as IL-1, IL-6,

and the tumor necrosis factor (TNF), further drives

the breakdown of protein and lipid while promoting the waste of fuel resources in futile paths such as

the Cori cycle.11,13,14

So what do we find when we consider the casualty? A young, previously healthy patient, whose

higher-than-normal physiological reserves have

been affected not only by his recent health and

nutrition but also by complicating stresses such as

cold or heat, anxiety, pain, volume loss, and infection. In general, heat is tolerated better than cold,

and a warmer environment is a better one for the

casualty. The presence or absence of military air

superiority will determine evacuation times, and in

many cases, the adequacy of resuscitation. The

length of time to evacuation, continued pain, volume depletion, and so forth, all effect the production of catecholamines, thyroid hormones, cortisol

glucagon and ACTH, and the inflammatory mediators, all of which, in turn, affect the metabolism of

the patient.

“Fatigue poisons” (ie, elevated levels of catecholamines, counterregulatory hormones, and inflammatory mediators brought on by the stress of combat or the prolonged stress of waiting for combat)

take their toll. Metabolism becomes less efficient,

receptors for catecholamines and thyroid hormones

down-regulate, glycogen stores slowly deplete, and

gluconeogenesis and ketosis are present at continual low levels. Catecholamines initially increase

both oxygen consumption and delivery, although

inflammatory mediators, as well as the catecholamines themselves, may interfere with both cardiac

output and the peripheral distribution of blood

flow. Arteriovenous shunting may actually decrease oxygen delivery to the tissues. The key to

metabolic control is adequate and continuing resuscitation to prevent both damage to enzyme systems

and cells and the formation of free-radical oxidation of tissues.15

Other factors (predominant among them volume

depletion and concomitant hypoperfusion of tissues) trigger or amplify a hypermetabolic response

to stress and injury. The initial state of the injured

patient, and the adequacy of initial and continuing

resuscitation at the first and second echelons and

during evacuation rearward, will determine the

efficiency of organ function, the generation of inflammatory mediators, and the subsequent medical

course of the patient. Cold and high glucose loads

may each promote a subtle diuresis that may be

overlooked during extended transport or if there

are large numbers of casualties. A significant limb

injury, delayed evacuation, and volume depletion

worsened by hypothermia may combine to create a

hypermetabolic state that will result in multiple

organ failure and death weeks after the injury.

Stages in the Response to Stress

Stress, whether emotional or physical (from illness, injury, or infection), induces specific patterns

of metabolic response in the body. The patterns

presumably evolved as a survival advantage, a

means to deal with overwhelming stimuli. They

work reasonably well most of the time but often at

great expense to the patient, as Shakespeare knew:

“Diseases desperate grown by desperate appliance

are reliev’d, or not at all.”16

The Immediate Response

The immediate response to stress is modulated

by the sympathetic nervous system, hypothalamus,

pituitary, and adrenals. The hypothalamus orchestrates the activation of the sympathetic nervous

system and stimulates the release of pituitary hormone and the production of glucagon by the pancreas. ACTH released by the pituitary increases the

production of cortisol and other steroids; these, in

turn, increase the breakdown of skeletal muscle

protein and the turnover of protein in the liver, as

well as the breakdown of hepatic glycogen for glu-
Metabolic Derangements and Nutritional Support

555

cose release. Catecholamines increase available

glucose by acting on skeletal muscle to increase

protein turnover, on lipid storage cells to release

free fatty acids, on the pancreas to increase output

of both glucagon and insulin, and on the liver by

promoting glycogenolysis and gluconeogenesis.

Steroids and glucagon also act to promote gluconeogenesis.12–14

Trauma causes a mobilization of resources to

deal with the injury, inducing a hypermetabolic

state in which oxygen and substrate consumption

are greater than normal the availability of ATP does

not necessarily increase correspondingly. Oxidative phosphorylation makes available, in the form

of ATP, about 40% of the energy that is available in

glucose. The remainder appears as heat. Unfortunately, the normal efficiency can be reduced by the

uncoupling of oxidation and phosphorylation as

well as by the appearance of futile cycles, which

consume oxygen and substrate but yield little net

gain in energy except for the production of heat

necessary for thermostasis.17 It is apparent that this

state will often be induced when the casualty is in a

preexisting stressed state and has limited reserves

for the new demands. The changes are different

from those of starvation but are similar to those

seen in the stressed state, although of a much greater

magnitude.

The state of hypermetabolism has been known by

a variety of names, including sepsis, sepsis syndrome, autocatabolism, and most recently as the

systemic inflammatory response syndrome (SIRS).

This syndrome is discussed in detail in Chapter 24,

The Syndromes of Systemic Inflammatory Response

and Multiple Organ Dysfunction, but a brief description of mediators and hormone responses is in

order here. The hypermetabolic response to stress,

especially trauma and infection, is orchestrated by

the activation of the neuroendocrine and cytokine

systems. The appearance and magnitude of the

mediator response depends directly on the severity

of trauma, the amount of inflammatory tissue

present, and the presence or absence of infection.

Mediators (peptide regulatory factors) are produced

by macrophages, lymphocytes, and other cells that

are reacting to a stress stimulus, and have both

paracrine and autocrine effects on other cells, inducing the expression of a variety of genes and the

synthesis of several proteins that mediate the inflammatory response. Two of the most important in

terms of metabolism are TNF and IL-1.

In addition to its role as an immune modulator,

TNF modulates a great deal of the metabolic response of the organism. Circulating levels of TNFα and TNF-β increase with stress and increase markedly with infection. Bacterial toxins are one of

many kinds of stimuli that activate production of

TNF in hepatic macrophages and lymphocytes. TNF

activates T and B lymphocytes and the production

of interleukins (specifically, IL-1 and IL-6), growth

factors, and eicosanoids—especially the lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade.11,12,15 The production and output of corticotropin, adrenal cortisol, glucagon, and

catecholamine are all increased in response. Fever,

a fall in white blood cell count, and hypotension are

the immediate results, followed by an increase in

white blood cells with a relative lymphopenia, an

increase in lactoferrin, and a fall in iron stores.

Collagenase synthesis increases, with reabsorption

of bone and cartilage. Formation of structural proteins other than at the wound site, albumin production, and the synthesis of nonessential proteins all

slow dramatically, while acute-phase protein synthesis in the liver, prostaglandin production, and

proliferation of fibroblasts at the site of injury all

markedly increase. Serum lipids increase as fat

stores are catabolized, and amino acid turnover

accelerates.3,11,13,15 Cytotoxic effects on certain cells—

the beta cells of the islets of Langerhans, for example—

decrease the availability of the anabolic hormones.3

IL-1 also has a broad spectrum of activity, from

acting as an inflammatory and immune mediator to

affecting metabolic, hematopoietic, and physiological functions. IL-1, the “endogenous pyrogen,” is

also responsible for fever, elevation of the white

blood cell count, increase in the level of colony

stimulating factors and other interleukins, and the

marked increase in acute-phase protein synthesis

by the liver. IL-1 also decreases iron levels; this may

be a protective mechanism, as bacteria deprived of

iron are less cytotoxic than those with easy access to

iron stores. Serum albumin and serum zinc levels

drop as zinc (as well as iron) is taken up by the

liver.3 A decrease in appetite is common, possibly

due to the decreased serum zinc. The release of

ACTH increases the production of adrenal steroids.

IL-1, like TNF, is cytotoxic to pancreatic beta cells.

Proteolysis is accelerated, as is hepatic uptake of

amino acids for gluconeogenesis and acute-phase

protein synthesis. IL-1 and TNF act synergistically

to produce acute-phase protein synthesis, the immune response, shock, and hypermetabolism as a

response to stress, injury, and bacterial invasion.

Other interleukins and eicosanoids amplify the response that the phrase “metabolic tide” describes.

Catecholamines, as well, respond to circulating

mediators and the urging of the ventromedial
Anesthesia and Perioperative Care of the Combat Casualty

556

nucleus of the hypothalamus. Epinephrine and

norepinephrine levels increase within 5 minutes of

injury, from both sympathetic nervous system stimulation and adrenal output. The degree of response

correlates directly with the degree of stress.13 The

catecholamines orchestrate the neuroendocrine response: glucose is released from the breakdown of

glycogen, and insulin release is inhibited at the

same time glucagon production increases. Serum

osmolality rises, which temporarily augments blood

volume (although to a lesser extent in the starving

or fasting patient). It is unclear to what extent the

decrease in insulin affects cellular glucose entry

early on, as glucose can enter hypoxic cells without

the need for insulin. Certainly, in a hypovolemic,

hypotensive patient, many tissues will have some

degree of hypoxia. Glucose will also move down a

concentration gradient, and as the serum glucose

concentration rises, more will enter cells; however,

the cells may not be able to utilize the glucose

effectively. In addition to the initial decrease in

insulin output, the peripheral tissues become less

responsive to insulin over time as insulin receptors

down-regulate. The shift to a catabolic state brought

on by the high levels of TNF, interleukins, catecholamines, steroids, and glucagon causes proteolysis and the release of amino acids from muscle

tissue. TNF directly inhibits lipoprotein lipase,

decreasing the availability of lipid fuel stores for

energy production. Both VO2 and the metabolic rate

increase, an increase that is directly linked to catechol production.12,13

Other hormonal balances change, as well. Thyroxine (3,5,3 ́,5 ́-tetraiodothyronine, known as T4)

production does not change, but the conversion of

T4 to 3,5,3 ́-triiodothyronine (T3) decreases markedly as T4 breaks down not to T3 but to the metabolically inactive reverse T3 (3,3 ́,5 ́-triiodothyronine).14

This decrease in metabolically active T3 is one of the

causes of the hyperglycemia common to the hypermetabolic state.18,19 The production of growth hormone increases during stress, which promotes protein synthesis; the increase is enhanced if two

stressors occur in a short period, such as a high

physical or emotional stress state followed by injury, or injury followed by infection. Arginine

vasopressin is released by the posterior pituitary

and acts to retain fluid. The adrenal glands pour out

corticosteroid in response to ACTH, catecholamines,

antidiuretic hormone, and growth hormone, increasing glucose intolerance. Erythropoietin production by the kidney increases, and the reninangiotensin axis becomes activated.

Once again, the ratio of insulin to glucagon plays

a major role. After an initial decrease following

stress, insulin levels may rise to far above normal,

but they never catch up with the rise in glucagon

production and release. The ratio of the hormones

is altered to favor catabolism, promoting glycogenolysis and gluconeogenesis. The counter-regulatory hormones, glucagon, growth hormone, catecholamine, and steroids keep glucose levels elevated. It is

often difficult to control hyperglycemia even with

massive doses of exogenous insulin. Triglycerides

are being converted to free fatty acids and glycerol

by high insulin levels, increasing lipase activity.

This action is overridden to large extent by the

counterregulatory hormones but still provides fatty

acids to fuel metabolic processes.13,14

Immediately after an injury, when blood flow is

directed to vital organs in an attempt to preserve

oxygen delivery, the insulin response to hyperglycemia is blunted: the beta cells of the pancreas

are delayed in responding to hyperglycemia, and

the response is less than normal for the level of

hyperglycemia. This is due in part to hypoperfusion,

and in part to the direct effects of catecholamines

and IL-1 and TNF on the beta cells.13 After resuscitation and stabilization, the insulin response to glucose is normal to increased, occasionally markedly

increased. Glucagon, however, has also increased,

and the ratio determines catabolism or anabolism.

Even when the rise in insulin production outstrips

glucagon output, the cells are less responsive to the

insulin. Cell-surface insulin receptors down-regulate in response to alterations in growth hormone

and cortisol, and there may well be a postreceptor

defect similar to that seen in non–insulin-dependent diabetes mellitus.13,15

The physiological response of the body to trauma

and sepsis has been classically described as having

two phases, an ebb and a flow.

13–15 The ebb phase

occurs during the first 24 to 48 hours after the stress

event, including the initial resuscitation, and is

characterized by hypodynamic circulatory and

metabolic responses. Cardiac output, temperature,

blood volume, and metabolic rate all decrease, as

though the tissues are stunned. Lactate levels and

body weight (from third-spacing of resuscitation

fluids) increase, often dramatically. Data for this

phase come from only a small number of patients,

and not all experts agree on the presence or importance of the ebb phase. While oxygen delivery does

decrease, recent data20,21 show this to be offset by a

rise in the oxygen extraction ratio of some tissues.

There is general agreement on the flow phase, how-
Metabolic Derangements and Nutritional Support

557

ever. Massive release of epinephrine and norepinephrine push hypercatabolism and the maximum

mobilization of nutrients. While the severity of the

trauma or sepsis dictates the course, the adequacy

of resuscitation dictates the duration of the active

phase and the eventual outcome. The shift to an

acute-phase response markedly increases the energy needs of the organism, and a massive mobilization of fuels, as well as of structural elements for

wound repair, occurs.15 The flow of substrate generally exceeds the requirements for energy. Tissues

adapt to the oxidation of other fuels. These processes will either shift to an adaptive response—

anabolism and repair—as the stimulus for inflammation is removed, or will continue to multiple

organ failure and death.

Changes in Organ Beds and Blood Flow

The response to stress is an adaptive mechanism

that makes substrates available to meet the body’s

metabolic needs. The substrates, however, may not

always go where they are needed. Microcirculatory

dysfunction is present in many organ beds and may

last days to weeks in some. Normal hepatic perfusion is not restored for 2 to 3 days after adequate

resuscitation. Both heat production and oxygen

consumption of injured tissue rise in the flow phase,

due to increased energy expenditure by the heart

and breakdown and recycling of lipid and protein—in some cases futile recycling. Oxygen delivery increases and total body oxygen consumption

rises, owing to the oxidation of mixed fuels. Carbon

dioxide production increases concomitantly, and

minute ventilation follows. The increase in total

oxygen consumption, however, may not reflect regional blood flow. While in most regions blood

flow rises, in some it remains depressed. Both the

renal and the splanchnic beds increase their oxygen

consumption, generally in proportion to the severity of injury, but changes in the microcirculation

may prevent an increase in oxygen delivery. Anaerobic means of ATP production ensue, with increase

in tissue lactate. “Adequate” blood pressure does

not necessarily mean adequate perfusion. Hypoperfusion is expected in the ebb phase and is vigorously treated. Epinephrine and norepinephrine

output rise rapidly in the first 5 minutes after trauma,

with elevation of vascular resistance and increased

shunting of blood. When this is superseded by the

flow phase, the metabolic rate increases and protein

catabolism begins. This usually maximizes at 4 to 8

days but persists until the stress stimulus resolves

or the injury is repaired. Hepatic blood flow and

oxygen consumption increase shortly after a stress

stimulus to allow the liver to meet the increase in

metabolic demand. In trauma with inadequate resuscitation, however, or with any combination of

sepsis, general anesthesia, or abdominal surgery,

hepatic blood flow decreases, limiting delivery of

both oxygen and nutrients. Renal blood flow

changes in much the same fashion, with a normal

increase in glomerular filtration rate to aid in the

excretion of toxins and urea. Daily loss of body

water generally increases, not only from insensible

losses due to fever but also due to this increased

glomerular filtration rate and the osmotic load resulting from hyperglycemia and the products of

tissue breakdown. While insulin output falls early

due to inhibited production in the pancreas, the

elevated catecholamines, cortisol, and growth hormone stimulate the alpha cells of the islets of Langerhans to release glucagon in large amounts. High

levels of their accustomed fuel, glucose, are made

available to all tissues, and the increased serum

osmolality helps to augment blood volume. As

levels of these catabolic hormones continue to rise

after resuscitation, insulin levels rise as well, often

to levels severalfold higher than normal. Cellmembrane insulin receptors down-regulate in response, and the hyperglycemia needed for cellular

operations under adverse conditions persists. Hepatic adenyl cyclase activates, acute-phase proteins

are produced, and both glycogenolysis and gluconeogenesis rapidly maximize.

Metabolic Changes in Trauma with Sepsis

Consider for a moment the massive energy expenditure as the body responds to the stress of

trauma or sepsis or both. Some cells must acutely

perform many times the normal work of the body by

• producing hormones, inflammatory mediators, and acute phase proteins;

• mobilizing host defenses and producing

new neutrophils, lymphocytes and antibodies;

• destroying invading bacteria;

• circulating greater-than-normal amounts of

oxygen and nutrients to all parts of the

body while removing increased volumes of

carbon dioxide; and

• directing nutrients to the wound and producing new protein for granulation tissue,

performing repair, and restructuring.
Anesthesia and Perioperative Care of the Combat Casualty

558

Protein synthesis continues in the face of catabolism,

although at a reduced rate; the resources merely shift.

Add to these the metabolic cost of processes

necessary to simply obtain fuel when the normal

logistics break down—glycogenolysis, proteolysis,

lipolysis and gluconeogenesis, generation of urea—

and we realize just how much energy production is

actually necessary, once the “hormonal tide” sweeps

in. Add to this the loss in efficiency of glucose

utilization. Although clearance of glucose by muscle

tissue rises, a lower fraction of the maximum potential energy available from glucose actually appears

as useful work, probably because the inhibition of

enzymes causes a decrease in the ability of pyruvate

to enter the TCA cycle. The increasing amount of

pyruvate and increased amounts of lactate, alanine,

and glutamine, are carried to the liver, where glucose recycles futilely in the Cori cycle. The high

levels of catechols and other mediators support this

recycling. Because of the abnormal glucose metabolism, many tissues switch from glucose to fatty

acids for fuel, and lipid becomes the primary energy source. Lipolysis occurs despite elevated levels of glucose and insulin. The actual utilization of

lipid varies, however, and appears not to be as

extensive as would be thought given the elevated

metabolic rate. Many tissues cannot utilize lipid

effectively, either, and futile cycling of fatty acids to

triglycerides and back occurs, at a net energy cost as

well as the penalty of fatty deposition in the liver.

Hormone- and mediator-driven muscle breakdown releases amino acids into the circulation, both

to increase the precursor pool for visceral protein

synthesis and to provide a ready fuel source.

Branched-chain amino acids, from structural proteins (skeletal muscle, connective tissues, unstimulated gut mucosa), donate their carbon skeletons for

conversion to glucose to support the increased metabolic rate of the liver. Glutamine, alanine, and the

aromatic amino acids are readily available for protein synthesis, while the availability of the branchedchain amino acids falls as they are used for fuel.

Leucine, released by the catabolism of skeletal

muscle, is in large part irreversibly oxidized in

muscle. This amino acid is essential to the utilization of other amino acids by the liver; if levels of

leucine fall, the liver can no longer efficiently utilize

other amino acids. These are broken down and

excreted. Total body protein synthesis is reduced,

although hepatic protein synthesis rises.15 Alanine

stimulates hepatic protein synthesis, with the synthesis of nonacute-phase proteins (ie, albumin and

transferrin) held in check by mediator release from

hepatic macrophages. Structural protein, however,

was never intended as an intrinsic energy source

except over the briefest time. Trauma initiates an

obligatory, normal catabolism over 24 to 48 hours,

to provide glucose when glycogen stores are depleted. Further stress stimuli—sepsis, for example—

will perpetuate and magnify this response. Lean

body mass becomes significantly depleted after 7 to

10 days, placing the patient in a poorer risk group

for survival.

Shifts in Oxidative Metabolism

Glucose is the preferred fuel for many tissues,

particularly the central nervous system and granulation tissue. The maximum rate of glucose oxidation for most tissues, however, is 3 to 6 mg/kg/min,

inadequate for cellular needs under these conditions. Ready supply of glucose is also limited, and

new glucose must be slowly mobilized from

noncarbohydrate sources. If exogenous calories are

provided, with the bulk from carbohydrate, then

nitrogen sparing will occur to a much lesser degree

than is seen in starvation. The RQ will remain below

1.0, indicating a failure to use glucose as a fuel, or may

climb to much greater than 1.0 as exogenous glucose

is used to make fat deposits in the liver. Some tissues

change over to other fuel sources in an effort to keep

up with the demand of the metabolic rate. An RQ of

0.75 to 0.85 generally indicates the use of mixed

fuel, most often lipid and protein.

Early response—prior to adequate resuscitation—

of oxidative metabolism to trauma or sepsis generally results in an oxygen debt, which itself results

from the sum of individual organ decrements in

oxygen consumption. Low levels of oxygen consumption are often due to hypoperfusion due to

hypovolemia, sepsis, or both; however, hypothermia, malnutrition, and sedation may all contribute

and should be considered. Total body oxidative

metabolism increases as the hypermetabolic response to a stress state develops. The increase in

oxygen consumption in the flow phase represents

the increase in total body consumption, and is directly proportional to the severity of injury and

adequacy of resuscitation. It peaks between days 3

and 10. Oxygen consumption of individual tissues

or organ beds may actually decrease, depending on

the state of their perfusion, so the total body oxygen

consumption does not necessarily reflect adequate

blood flow to all tissues.

As glucose stores are consumed, a shift to lipolysis and proteolysis provides free fatty acids, alanine, and glutamine for the TCA cycle. Unfortunately, a significant portion of the lipid is squandered
Metabolic Derangements and Nutritional Support

559

to make additional triglycerides, driven by high

insulin and glucose levels.3 Amino acids become

the chief fuels for the TCA cycle. While there is an

absolute increase in the oxidation of lipid and glucose, the percentage of calories derived from these

two sources declines steadily. The rate of endogenous glucose production from all sources increases,

but glucose concentrations remain stable, although

elevated, because of a matching rise in glucose

uptake. Glucose turnover is proportional to total

body oxygen consumption, which, in turn, is proportional to the severity of injury or infection. Regional uptake of glucose, though, is related to regional blood flow, and is generally matched by

regional lactate release, but is not directly related to

regional oxygen consumption. It is the combination

of a steep glucose gradient and the diversion of

blood flow to regions of inflammation that drives

regional glucose uptake. The glucose is often converted to lactate via glycolysis in areas of inflammation, even if oxygen delivery is adequate. As a

result, regional oxygen consumption is not predictive of regional glucose utilization.

Serum lactate rises as a consequence of hypoperfusion, but it is a late indicator of that state. Most

tissues will tolerate a partial pressure of oxygen as

low as 30 torr before excessive lactate generation

occurs. Both (a) catecholamines driving gluconeogenesis and glycolysis and (b) decreased hepatic

perfusion will raise lactate levels significantly: the

first by generation of lactate; the second by limiting

clearance.

Endogenous glucose is produced by the liver

from a number of precursors. Lactate, alanine,

glutamine, glycine, serine, and glycerol are all substrates that can be used to produce glucose, although several of the mechanisms are futile pathways. Since gluconeogenesis consumes energy, the

limited ATP generated at the tissue level from the

new glucose is balanced by the loss in the liver. The

net energy gain for the total body is zero, although

the heat produced may be necessary for maintaining thermal neutrality.17 The site of the wound or

inflammation does, however, gain 2 moles of ATP

for each mole of glucose consumed, and a few

tissues, such as myocardial cells, can utilize lactate

directly via the mitochondrial malate shuttle. Alanine can also be converted to glucose and, in fact, is

the major source of new glucose. The conversion of

alanine to glucose requires the use of ATP and

generates urea, the excretion of which requires that

further energy be expended. The high-energy phosphate pool gradually shrinks through losses of TCA

cycle efficiency and the loss of labile proteins.

Because of the increased lipolysis that develops a

few days after injury, fatty acid deficiencies can

occur early. Following trauma, there is a 55% increase in the rate of lipid oxidation; following infection, a 25% increase.22 The lesser increase in lipid

utilization during infection is thought to be due to

the impaired activity of lipoprotein lipase by TNF,

IL-1, and IL-2.23 These are not suppressed by carbohydrate feeding, a difference from the oxidation in

simple starvation; nor is there an increase in ketones, which are used as fuel under these circumstances. Long-chain, essential fatty acids, linoleic

and arachidonic in particular, rapidly decrease after injury. Essential fatty acid deficiency can develop after 2 to 3 weeks, and requires a minimum of

10% of exogenous calories in the form of lipid to

prevent.

Protein Turnover and Preferential Amino Acid

Utilization

Protein turnover increases with stress, and increases dramatically with trauma or sepsis (Figure

23-8). The level may be taken as a measure of the

severity of the stress event. As we discussed earlier,

glucose stores are used early, leaving the body to

depend on lipid calories and, for those obligate

glucose-using tissues, on amino acids and glycerol

to generate additional glucose. Protein turnover is

also increased to free amino acids for production of

acute-phase proteins, including TNF and the

interleukins, and for wound repair. Both proteolysis and hypermetabolism peak shortly after the

onset of the stress state, gradually returning to

normal as recovery progresses. The catabolism

results in early and rapid muscle wasting.

Branched-chain amino acids from muscle tissue

are deaminated and their carbon skeletons oxidized

in the TCA cycle for the vastly increased metabolic

processes. The rate of protein catabolism can surpass 300 g/d of muscle protein, or nearly 50 g/d of

nitrogen lost.24 Skeletal muscle makes up as much

as 80% of the free amino acid pool,13 with the bulk of

this intracellular. A 70-kg man has roughly 87 g of

free amino acids in the intracellular space but less

than 2 g extracellularly. Protein catabolism is largely

an intracellular event, with the changes in skeletal

muscle tissue due to changes in the intracellular

pools. Breakdown of body protein stores and urinary loss of nitrogen parallels the REE. Hepatic

blood flow increases dramatically to meet the hypermetabolic demand. Those amino acids not used

to form new protein are deaminated in the liver for

their carbon skeletons and their amino groups used
Anesthesia and Perioperative Care of the Combat Casualty

560

Fig. 23-8. Metabolic interrelationships

in the wounded casualty. The wound

is an obligatory user of glucose,

which, for the most part, is derived

from amino acids by the process of

gluconeogenesis. Glucose is metabolized by glycolysis in the wound,

forming lactate. The lactate is then

transported back to the liver where it

is reconverted to glucose. This process is known as the Cori cycle and,

being energy demanding, is one of

the determinants of the hypermetabolic state that characterizes trauma.

Two amino acids released by the catabolism of skeletal muscle are of special importance: alanine, which is

transported to the liver to form glucose; and glutamine, which forms the

primary substrate of the intestines.

Reprinted with permission from

Bessey PQ. Metabolic response to

critical illness. Chap 11. In: Part 2.

Care in the ICU. In: Wilmore DW,

Brennan MF, Harken AH, Holcroft

JW, Meakins JM, eds. Vol 1. Critical

Care. In: Care of the Surgical Patient.

New York, NY: Scientific American,

Inc; 1989: 11-11.

for the synthesis of glutamine and alanine. The

concentrations of glutamine and alanine in blood

are greater than would be expected from their concentrations in muscle protein, indicating both synthesis in and net release from myocytes. Glutamine

has two essential functions: (1) it is the preferred

substrate for oxidative phosphorylation in the gut,

and (2) ammonium ions from glutamine are used in

the kidney to buffer metabolic acids.

Glutamine makes up a large part of the “buffer

pool” of amino acids. This nonessential amino acid

makes up 5% to 6% of the total body protein, and

60% of the total intracellular free amino acid pool25

(the eight essential amino acids together make up

only 8.4 % of the intracellular pool). Body proteins

are not intended to be a long-term energy source.

They are structural components, and their loss interferes with a broad spectrum of body functions

(eg, locomotion, immunological competence). The

level of intracellular glutamine falls rapidly with

stress, starvation, and after surgery or trauma, as

glutamine is transported to the gut and converted

to alanine to be fed into the TCA cycle in the liver.4,26,27

The extent of the fall in glutamine levels seen with

sepsis parallels the severity of the sepsis. Intracellular concentrations of other amino acids—leucine,

isoleucine, valine, alanine, phenylalanine, and tyrosine—rise in stress, trauma, and sepsis, reflecting

the catabolism present in the muscle. As they are

used to fuel the metabolic engines, levels fall. As

the branched-chain amino acid levels decline in

sepsis or after severe trauma, the level of aromatic

amino acids rises, and the ratio between the two

shifts.4

Protein synthesis continues even as proteins are

catabolized. New cells are built; antibodies, coagulation factors, cytokines, and so forth are elaborated: the shift is from maintenance of general structural elements to defense and wound healing.

Probably even more than the neurohormonal controls, the inflammatory mediators are responsible

for the degree of hypermetabolic response. When

more than 20% of the lean body mass has been

lost—generally after 7 to 10 days without nutri-
Metabolic Derangements and Nutritional Support

561

tional support—insufficient substrate remains to

support synthetic function. After 14 days, the wound

will be catabolized and is likely to dehisce. What is

left is used as fuel, with decreasing efficiency, until

the patient dies.14,15 Lean body mass cannot be

regained so long as the inflammatory mediators are

present, although loss of nitrogen can be countered

with aggressive feeding. Feeding with a formula

high in branched-chain amino acids—leucine, isoleucine, and valine—may ameliorate the protein

loss to a greater degree than with standard amino

acid formulas. These are preferentially oxidized by

muscle, providing nitrogen and energy for skeletal

muscle synthetic processes, as well as carbon skeletons for glucose-requiring tissues. Indeed, in the

face of insulin resistance and lipase dysfunction,

branched-chain amino acids may be the single best

source of fuel for a hypercatabolic patient with

organ dysfunction.4,28,29

As the structural proteins redistribute to areas of

increased metabolic need (ie, the visceral organs,

macrophages, and wounds) to support acute-phase

protein synthesis, nonacute-phase protein synthesis (albumin and transferrin) declines. Hepatic cells

release mediators such as nitric oxide, IL-6, and

granulocyte-macrophage colony stimulating factor,11,13,15,30 which maintain the release of inflammatory mediators from the Kupffer cells in an

autoamplifying cascade. The effects can persist for

days after the initial stress stimulus has been removed, driving the hypermetabolic response. Tissue repair does not begin until late in the flow

phase, during the adaptive phase, when the metabolic processes organize and regularize. This is the

phase when nutritional support is the most effective for rebuilding structural proteins; the body is at

last able to respond to exogenous nutrition by increasing cell mass rather than by merely minimizing losses.

Energy Requirements of Patients With Injuries

or Infections

All stress states increase the metabolic requirements of the patient to some degree, which can be

estimated by a rule of thumb (Table 23-2). A simple,

uncomplicated surgery will increase energy requirements by 5% to 10% over the REE. Multiple trauma

or sepsis increases requirements by 30% to 55%;

a mechanically ventilated patient with sepsis or

trauma has energy requirements 50% to 75% over

REE. As a comparison, while doing manual labor,

a normal person has energy requirements approximately 100% to 400% above REE. For example, if

TABLE 23-2

PREDICTION OF CALORIC REQUIREMENTS

IN STRESSED PATIENTS*

Patient Status Correction Factor

Confined to bed 1.2 • REE

Ambulatory 1.3 • REE

Fever (1.0 + 0.13 per °C) • REE

Peritonitis 1.2–1.37 • REE

Soft-tissue trauma 1.14–1.37 • REE

Multiple fractures 1.2–1.37 • REE

Sepsis 1.4–1.8 • REE

Burns (as % TBSA)

0–20 1–1.5 • REE

10–40 1.5–1.85 • REE

40–100 1.5–2.05 • REE

*Based on alterations in their metabolic rate

REE: resting energy expenditure; TBSA: total body surface area

Data source: Zimmerman JE. Nutritional support in the ICU.

Lecture presented at Update in Critical Care—1993; April 1993;

Washington, DC.

basal metabolism equals 1 kcal/kg/h, and if intense

manual labor requires 5 kcal/kg/h (400% above

normal), but this level of activity persists for only

one fourth or one third of the day, then the manual

laborer’s energy requirements are approximately

100% higher than normal.

Oxygen consumption rises to match the increase

in REE. Normal resting VO2 averages 100 to 125

mL/min/m2; consumption in a severely stressed

patient may be greater than 170 mL/min/m2 (in

general, the higher the consumption can be raised—

by altering the available partial pressure of oxygen,

available hemoglobin, and cardiac output—the

greater the chance for survival). Failure to alter DO2

and thereby successfully raise VO2 generally ends

with a poor outcome.31

Energy requirements can be estimated for individual patients in a number of ways; unfortunately,

many of the techniques do not lend themselves to

battlefield application. Nutritional assessment by

intake and weight history is valuable but difficult to

obtain in the field. Indirect calorimetry is a moderately useful tool but requires special equipment, a

stringent metabolic steady state during measurement, and will only give a “snapshot”—the require-
Anesthesia and Perioperative Care of the Combat Casualty

562

Fig. 23-9. This nomogram provides estimates of the caloric intake required for weight maintenance in patients with

various disease processes. If the point that represents the patient’s body weight on the scale at left is connected by a

straight line to the point that represents the patient’s disease process on the scale at right, then estimates for the

patient’s caloric requirement and metabolic rate can be read off the left and right sides of the middle scale, respectively.

This nomogram should be used only for patients from 15 to 45 years of age whose height is normal. Reprinted with

permission from Wilmore DW. Metabolic Management of the Critically Ill. New York: Plenum Press; 1977: 36.

or BMR based on a combination of body weight and

disease process (Figure 23-9). Other specialized tests

for nutritional assessment are discussed below.

Medical officers must keep in mind that REE will

change with feeding. A casualty with a burn to less

than 10% of his body surface area will have an

increase in REE of 6% to 7% if unfed. Feeding will

increase this by a factor of 5; overfeeding will result

ments at the time of measurement. Linear-regression formulas frequently overestimate energy requirements. Any of these may be used, so long as

the shortcomings of each are borne in mind. Probably the best method of estimating nutritional state

and energy requirements, whether in the field or at

a fourth- or fifth-echelon hospital, is by a combination of the physical exam and tables that define REE
Metabolic Derangements and Nutritional Support

563

in an even greater increase. It requires energy to

process fuel and building material. This is known

as the specific dynamic effect. A mixed-fuel diet

(carbohydrate and fat) will be less costly in terms of

energy than an all-carbohydrate or an all-fat diet,

and the energy expended to process enteral feeding

is significantly less than that used to process

parenteral nutrition.

The RQ changes with injury or sepsis. In the

stressed state, the RQ is initially between 0.75 and

0.85, reflecting the mixed oxidation of carbohydrates, fats, and proteins in aerobic glycolysis and

the TCA cycle. Lipolysis increases, as does release

of lactate and pyruvate from muscle tissues, wound

tissue, and macrophages and monocytes. The ratio

of lactate to pyruvate remains normal, and the redox potential of the mitochondria is unchanged. As

SIRS develops, the mitochondria increase their capacity to oxidize the two-carbon fragments being

fed to them, and the RQ rises slightly. As organs

become less functional, the RQ continues to rise,

indicating a net lipogenesis, often aided by overfeeding total calories or carbohydrate.

Oxygen Consumption and Oxygen Delivery

Both oxygen consumption and delivery increase

with sepsis or injury, modulated by the elevation of

catecholamines. Should sepsis/SIRS progress to

shock, both oxygen consumption and REE fall sequentially.15,21 This progressive decrement in the

metabolic response reflects both the maldistribution

of blood flow and the impairment of oxygen extraction that are characteristic of the state, as well as an

enzymatic failure at the mitochondrial level that

inhibits the TCA cycle. The rise of endotoxin levels

matches the fall in metabolic rate. As oxygen delivery falls further, an oxygen debt is incurred and

lactate accumulates, shifting the ratio of lactate to

pyruvate, with a resultant metabolic acidosis.31

Reversal of the shock state restores the hypermetabolism, driven by catecholamines and inflammatory mediators, but only restoration of adequate

oxygen delivery will reverse the oxygen debt and

the lactic acidosis.

Patterns of Response

The pattern of response to stress—injury or infection—is standard regardless of the inciting insult,

presumably because of a survival advantage to the

pattern. The response involves the liver, skeletal

muscle, gut, kidneys, and heart, and the wound or

focus of inflammation. The neuroendocrine system

and the cytokine-mediator system act interdependently to bring about the characteristic changes,

with the neuroendocrine stress response amplified

many times by cytokine mediators, and vice versa.

Norepinephrine increases endotoxin-induced TNF

production, while TNF pushes ACTH and growth

hormone production and alters thyroxine conversion,

and glucocorticoids feed back to decrease transcription and posttranslational processing of TNF and IL1.11,13 The focus of the inflammatory response acts as

a physiological arteriovenous shunt, increasing cardiovascular work and restructuring oxygen delivery. It is often a site of tremendous metabolic activity,

with killing of bacteria, removal of dead bacteria and

necrotic material, and wound repair continuously

going on. The focus may be relatively hypoxic and

depend on glycolysis for energy, with production

of lactate and heat. Lactate and catabolized proteins are transported to the liver, where lactate,

glutamine, and alanine are converted to glucose,

which is returned to the focus of inflammation.

Creatinine, creatine, potassium, and magnesium are

all released. The ammonia produced by the catabolism of amino acids helps to neutralize acid loads,

which must be excreted by the kidney.13 Skeletal

muscle and the mucosa and smooth muscle cells of

the gut are also catabolized for fuel and amino acids.

The gut loses its normal immunological function soon

after injury, and after that, the ability to mechanically

block bacteria and bacterial products from the bloodstream. Stimuli from intestinal bacteria now add to

the inflammatory burden. This catabolism cannot

be stopped by feeding, but exogenous amino acids

can be utilized for both fuel and protein synthesis.

(For further discussion of this process, see Chapter

24, The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction).

Should the inflammatory stimulus be removed at

this time (by antibiotic treatment, removal of necrotic tissue, wound healing, etc), metabolism enters

an adaptive phase, where output from the paraventricular nuclei of the hypothalamus decreases, sympathetic activity follows, cortisol and glucose levels

fall, and the ratio of insulin to glucagon becomes

more appropriate, although still less than normal.

Fluids are mobilized, the urinary urea nitrogen

decreases and ketones are spilled into the urine.

The trend is toward a positive nitrogen balance,

although the metabolic rate is still high. Caloric

intake may need to be 1.5- to 2-fold higher than the

REE to stop protein catabolism, even at this point.

The metabolism gradually becomes anabolic.
Anesthesia and Perioperative Care of the Combat Casualty

564

If the inflammatory stimulus is excessive or prolonged or both, the neuroendocrine and cytokine

responses to injury gradually erode the metabolic

and immunological reserves. The transition to organ dysfunction comes about from a combination of

microcirculatory hypoxia, mediator-induced injury,

and toxin-induced injury to cells. Four classic phases

have been identified: shock, resuscitation, persistent hypermetabolism (ie, SIRS), and organ dysfunction.15 Shock and resuscitation affect primarily

the microcirculation and the endothelial cells; the

success or failure of the initial therapy sets the

course for subsequent events. Four to six days after

injury or infection, systemic inflammation and altered organ function are seen. Oxygen consumption increases. Oxygen delivery must match for the

patient to survive, so cardiac output and minute

ventilation follow the rise in oxygen consumption.

The RQ is now between 0.78 and 0.82, and the

proportion of calories from glucose and fat has

dropped. This hypermetabolic pattern will peak in

3 to 4 days, and if the inciting stimulus—infection,

persistent perfusion deficit (ie, inadequate resuscitation), local inflammation, or necrotic tissue—is

corrected, it should resolve in 7 to 10 days. A

portion of these patients, particularly those with

prolonged SIRS with shock, will develop a hypermetabolic state that will persist for 14 to 21 days,

even if the cause is corrected. If the inciting stimulus remains, the condition will progress to organ

dysfunction.

The transition from hypermetabolism to multiple organ dysfunction syndrome (MODS) is usually due to a persistent, often unrecognized, perfusion deficit; a new or resistant focus of infection; or

a persistent focus of inflammation. The actual death

of a certain mass of cells is probably not the explanation for progressive organ dysfunction; rather,

an increasing dysfunction of cellular subsystems to

a certain critical point is the likely mechanism.12,15

Microbial toxins directly inhibit intracellular

glycolytic enzymes and intracellular hepatic protein synthesis; mediators such as TNF and IL-1

inhibit lipoprotein lipase, cytochrome P450, and

albumin and thyroglobulin production; and products of metabolism in one region (eg, arachidonic

acid metabolites) adversely alter metabolism in others. Hydrogen ion shuttles, electron transport systems, and gating proteins are all parts of the clockwork mechanism that enters a state of metabolic

dysregulation.

Oxygen consumption becomes flow dependent

as the ability to extract oxygen decreases and lactate

production rises. A state of subclinical flow-dependent (inadequate) oxygen consumption may be

present in SIRS even without shock, or in the adult

respiratory distress syndrome, or pancreatitis, leading to MODS.

If refeeding has not begun by 7 to 10 days, then

metabolic failure based on loss of a critical amount

of body mass becomes a factor. As the breakdown

and redistribution of lean body mass continues and

approaches 20%, acute-phase protein synthesis begins to fail. The combination of (a) the loss of

structural protein and (b) dysfunction of the remaining systems due to continuing catabolism will

in itself cause organ dysfunction, and will also

greatly amplify toxin- and mediator-induced organ

failure. The transition from a hypermetabolic state

to MODS is a significant prognostic event, raising

the probability of death from 25% to 40% to 40% to

60% in the early stages of organ dysfunction,15 to

90% to 100% in the later stages.15,32 Wound healing

and immune function suffer early in organ dysfunction, but impairments of the kidney and liver have

the greatest impact on the deranged metabolism.

Metabolic requirements are especially increased in

uremia. Potassium, phosphates, and magnesium

all rise; pH falls; and the patient becomes both

volume and protein intolerant. Naturally, hypermetabolism accelerates these processes. Hepatic

failure means that the liver no longer efficiently

deaminates and transaminates amino acids.

Branched-chain amino acids are still used, leading

to an imbalance in the ratio between branchedchain and aromatic amino acids. False neurotransmitters are generated, leading to encephalopathy.

Effects on lipid metabolism vary, with some

patients able to metabolize large amounts of

exogenous lipid and others developing severe

hypertriglyceridemia (Zieve’s syndrome) and, occasionally, pancreatitis.

Treatment of the metabolic derangements—with

early, aggressive feeding; correction of flow-dependent oxygen consumption (or maximizing oxygen consumption where it cannot be corrected); and

improving perfusion of all organ beds, as measured

by tissue pH (ideally) or serum lactate (practically)—

assure that morbidity and mortality are markedly

reduced. The goal is to overcome the catabolic state,

or, where this is impossible, to allow (a) protein

synthesis to continue in the face of catabolism and (b)

the cellular mechanisms to repair themselves and

correct the hypermetabolic state. Enteral feeding, in

particular, restores the mucosa of the gut and alters

translocation of bacteria and bacterial products.
Metabolic Derangements and Nutritional Support

565

NUTRITIONAL SUPPORT

In general, it is easier to feed a malnourished

patient—with the proviso that we carefully observe

for hypophosphatemia—than a hypermetabolic patient. The results are also more clearly beneficial in

the former case. Some recommendations for nutritional support suggest that “nutritional support

should be considered if the patient has been without nutrition for 5 to 7 days”27(p3) and that “deficits

occur in critically ill patients after 7 to 10 days of

starvation.”27(p3) However, “starvation rarely assists recovery from critical illness.”33 Most intensive care specialists would begin support 24 to 48

hours after the ebb phase. Nutritional support

should be formulated according to the type and

severity of the injury or illness, the presence and

degree of organ dysfunction, electrolyte abnormalities, and glucose tolerance. Energy requirements

are primarily related to age, gender, body size,

and activity. In hospitalized, physically intact patients, the REE is the major caloric expenditure (see

Figure 23-9).

The magnitude of the increase in the REE in an

injured or septic patient is proportional to the degree of injury and the amount of support given. The

total energy expenditure (TEE) is the REE plus the

thermic effect of food (TEF) and the energy expenditure of activity (EEA). The goal in feeding the

patient is weight maintenance, corrected for fluid

gains and losses. Generally, 1,800 to 2,200 kcal/d is

required for this. Baseline protein requirements are

0.8 grams of protein (or 0.128 g of nitrogen) per

kilogram of body weight per day, increasing with

the degree of catabolism as established by the severity of trauma. The ratio of nitrogen to calories is

roughly 1:150, but may be as low as 1:200 or as high

as 1:100. The gut is the preferred route for providing nutritional support, but many times it cannot be

used.

Nutritional Assessment

Several methods are used to assess caloric needs.

Indirect calorimetry is in common use and may be

easily performed with only a metabolic cart and a

trained operator. Unfortunately, it requires that the

patient remain in a strict steady-state condition

during the period of measurement (eg, no changes

can be made in ventilator settings, the patient is not

allowed to move). Caloric requirements are based

on calculation of oxygen consumption using the

Fick method:

VO2 = (CaO2 – CvO2) • C.O.

VCO2 = (CvCO2 – CaCO2) • C.O.

where VO2 represents oxygen consumption per unit

time, CaO2 represents arterial oxygen contents, CvO2

represents venous oxygen contents, C.O. represents

cardiac output, VCO2 represents carbon dioxide consumption per unit time, CaCO2 represents arterial

carbon dioxide contents, and CvCO2 represents

venous carbon dioxide contents.

When calculated by gas exchange in indirect calorimetry, these become:

VO2 = (VI • FIO2) – (VE • FEO2)

VCO2 = VE • FECO2

where VI represents the inspired volume per unit

time, FIO2 represents the fraction of inspired oxygen, VE represents the expired volume per unit

time, FEO2 represents the fraction of expired oxygen, VCO2 represents carbon dioxide consumption

per unit time, and FECO2 represents the fraction of

expired carbon dioxide.

The required caloric input can be written as follows34:

REE (in kcal/min) = 3.581 (kcal/L) •

VO2 in L/min + 1.448 (kcal/L) •

VCO2 in L/min – 1.773 (kcal/g) • Nu in g/min

where Nu represents nitrogen excreted in the urine.

Even small fluctuations in FIO2 or VO2 can alter

the value for oxygen consumption. If properly

measured, oxygen consumption is quite accurate

over the period of measurement, but it is difficult to

extrapolate to a 24-hour period in an unstable patient or a patient with varying levels of activity.

Linear-regression–derived “standard” equations

generally overestimate caloric needs but may be

useful under field conditions. The Harris-Benedict

equation,35 the one most commonly used at military

teaching hospitals, uses separate formulas for men:

REE (kcal/d) = 66.47 + (13.75

• kg body wt) + (5.0 • height in centimeters)

– (6.76 • age in years)

and women:

REE (kcal/d) = 65.51 + (9.56

• kg body wt) + (1.85 • height in centimeters)

– (4.68 • age in years)
Anesthesia and Perioperative Care of the Combat Casualty

566

Probably the simplest, and often the most accurate, method for field use is a combination of standard tables based on body surface area and gender,

and a physical examination of the patient. (An even

quicker rough estimate: at rest, men consume

roughly 25 kcal/kg/d; women, 20 kcal/kg/d.) All

caloric estimates are for nonprotein calories.

The severity of the trauma or degree of stress increases the requirement for calories. Most critically

ill patients require 25 to 35 kcal/kg/d. Patients

with severe burns and trauma may require 35 to 45

kcal/kg/d, as may those patients who were severely calorie- and protein-depleted prior to injury.

Patients on ventilators—at least those whose ventilation is adequately controlled—have a generally

lower requirement, often less than 25 kcal/kg/d

(30% of caloric input may be required for ventilation in a nonintubated, critically ill patient).

Protein requirements are initially determined by

energy requirements, degree of malnutrition, and

severity of injury, then adjusted by following the

amounts of urinary urea nitrogen. Generally, the

urinary urea nitrogen plus unmeasured nitrogen in

the stool (approximately 3 g/d) are taken to be the

daily protein requirement. Protein replacement can

be guided somewhat more closely by calculating

the catabolic index (Exhibit 23-2); the goal is to

obtain a low number (< 0 is ideal).36

The goals of nutritional therapy are commonsense

goals:

• to restore nitrogen balance;

• to provide the appropriate amount of fuel

to maintain lean body mass;

• to provide appropriate vitamins, minerals,

and trace elements; and

• to avoid overfeeding with any nutrient, but

particularly to avoid overfeeding calories.

Excessive calories are converted to fat, particularly

in the liver; this shifts the RQ to much greater than

1.0, increasing oxygen consumption and minute

ventilation requirements markedly. Caloric overfeeding also depletes potassium and stimulates the

release of catecholamines and the formation of lactate, while failing to suppress gluconeogenesis or to

alter catabolic or synthetic rates. Overfeeding enterally can result in increased bacterial growth, gas

production, and bowel distention.

In general, the sicker the patient, the poorer the

accuracy of any of the means of estimating the

metabolic rate. Remember also that before any

benefits are derived, feeding imposes its own metabolic demands on the patient: increasing oxygen

consumption, carbon dioxide production, and ventilatory drive, as well as increasing the workload of

the cardiovascular system. A number of empirical

correction factors have evolved to improve our ability to estimate calorie and protein requirements of

the severely ill. Energy requirements increase 10%

to 20% with fever; 30% to 50% with the perioperative

state, sepsis, multiple trauma, head injury, or acute

renal failure; and 50% to 100% with severe burns or

seizures. Energy requirements decrease with paralysis, mechanical ventilation, hypotension, and

unstressed malnutrition (see Figure 23-9).

As a general guideline, a critically ill patient will

consume 25 to 35 kcal/kg/d; this is often useful as

a starting point for nutritional replacement. Protein

requirements are somewhat simpler to estimate.

The nitrogen to calorie ratio should be roughly

1:150, although with severe trauma this may rise to

1:100 (1 g nitrogen is equivalent to 6.25 g protein).

In ongoing protein catabolism with a rising blood

urea nitrogen (BUN) and increasing ratio of BUN to

creatinine, increased calories may ameliorate catabolism to some degree, and a nitrogen-to-calorie

ratio of 1:200 may be more appropriate. A greater

caloric intake will also be necessary to maintain a

positive nitrogen balance at a lower level of protein

intake. In general, protein requirements may be

estimated by severity of stress.

Acute renal failure, hepatic failure, and MODS

all restrict the body’s ability to meet its protein

EXHIBIT 23-2

CATABOLIC INDEX

Catabolic Index = 24-h urinary urea nitrogen

(UUN) excretion – (0.5 •

dietary nitrogen intake + 3 g)

< 0 No stress

0–5 Moderate stress

> 5 Severe stress

The catabolic index makes two important

assumptions:

1. obligatory UUN excretion is 3 g/d, and

2. 50% of ingested protein is utilized.

Data source: Bistrian BR. A simple technique to estimate

the severity of stress. Surg Gynecol Obstet. 1979;5:54–61.
Metabolic Derangements and Nutritional Support

567

requirements. Bear in mind that catabolism is not

sensitive to exogenous amino acids, but synthesis is.

Protein feeding will not reverse catabolism but will

increase the synthetic rate until it catches the catabolic rate and restores the nitrogen balance.

What nutrients are essential in formulating a

nutritional support plan? The standard total

parenteral nutrition (TPN) formula used at Walter

Reed Army Medical Center, Washington, D. C.,

includes carbohydrate sufficient to provide 50% to

70% of the estimated caloric need (3.4 kcal/g); lipid

to provide a minimum of 10% of calories (9 kcal/g)

and to prevent fatty acid deficiency (essential fatty

acids, chiefly linoleic acid, must make up 1%–2% of

total calories, roughly 2–4 g/d); essential amino

acids; electrolytes; vitamins; and trace elements

(Figure 23-10).

Parenteral Nutrition

The parenteral route is not the best way to provide nutritional support but is often the only route

available when delay would compromise the patient. Standard TPN uses hypertonic glucose—

25% or 50%—as a primary source of calories, with a

10% lipid solution to provide additional calories

and essential fatty acids. The carbohydrate is oxidized directly, with an RQ of 1.0, while the exogenous lipid is generally added to the fat stores and

mobilized as needed to be processed into fatty

acids and glycerol. A combination of the two

sources provides essential fatty acids, avoids

hyperglycemia, stimulates insulin production, and

decreases carbon dioxide production. A 6.9% to

10% amino acid solution is added, depending on

the formulation, and the resulting mixture diluted

to a tonicity of 1,900 to 2,000 mOsm/L. As this

solution is administered, via a central line in the

superior or inferior vena cava, it is rapidly diluted

to a nearly isotonic osmolality. The solution provides 0.85 to 1.1 kcal/mL, and 2 to 2.5 L/d will

generally provide adequate protein and calories for

any degree of stress.

Standard amino acid formulations have 19% to

25% branched-chain amino acids in a balanced mix

with other amino acids. Because catabolism of

protein in muscle is the primary source of the

branched-chain amino acids used by the liver for

gluconeogenesis (branched-chain amino acid

aminotransferases are primarily found in skeletal

muscle), and leucine, in particular, seems to have

anticatabolic properties (a dose-dependent ability

to decrease catabolism and possibly increase synthesis of muscle proteins as well as improving the

synthetic efficiency of the liver), many intensive

care specialists recommend using an amino acid

formula that is higher in branched-chain amino

acids. These modified amino acid formulations

contain roughly 45% branched-chain amino acids.

While nitrogen balance, and possibly immunocompetence, are improved, a clear improvement in outcome has yet to be shown.4

Replacement Minerals

Minerals must be added to the TPN solution,

both to replace those lost during hypercatabolism

and owing to the osmotic load of feeding. Magnesium, calcium, potassium, and phosphorus are all

used in increased amounts during hypermetabolism. Rather large amounts of magnesium (> 30

mEq/d), potassium (> 100 mEq/d), and phosphorus (as phosphate, 20–30 mmol/d) are often required. Injury and carbohydrate loads both increase the loss of potassium, as does the fall in

plasma magnesium seen after trauma or even elective surgery. Cell membranes become “leaky” after

trauma or sepsis, and the intracellular concentration of sodium rises while potassium dips. When

the patient improves, extracellular potassium loss

accentuates because anabolism drives the uptake of

potassium. Hypokalemia can easily result, especially if the patient is diuresing by this time. Seventy to one hundred milliequivalents of a potassium salt is required each day—more if the patient

is either hypercatabolic or actively diuresing. Sodium is generally less problematic. One-half to

two-thirds normal saline (75–100 mEq/L) is generally adequate to keep plasma sodium in the 135 to

145 mEq/L range. Patients who have received a

large sodium load during resuscitation or surgery

may more appropriately be given one-third normal

saline (50 mEq/L) as a maintenance dose to avert

hypernatremia. Sodium input should also be reduced in patients who are actively diuresing, because more free water than solute is lost and these

patients can easily become hypernatremic. If frequent adjustments to the sodium or potassium content of the TPN are necessary, it is more practical to

establish a lower, fixed amount of each cation for

the TPN and to administer additional salt as shortrun piggyback intravenous infusions.

Phosphorus is a vital electrolyte, and costly in

terms of lessons learned. Feeding the survivors of

concentration camps after World War II resulted in

an unexpectedly high number of deaths.37 It took a
Anesthesia and Perioperative Care of the Combat Casualty

568

MEDICAL RECORD—SUPPLEMENTAL MEDICAL DATA

For Use of this form, see AR 40-66; the proponent agency is the Office of The Surgeon General.

ADDITIVES/INSTRUCTIONS

[ ] Multi-Vitamins 10 mL or per day [ ] Cimetidine 900 mg or mg per day [ ] Reg. Human Insulin units per day

[ ] Multi-Trace-5 4 mL or per day [ ] Famotidine 40 mg or mg per day [ ] Other:

[ ] Additional Zinc 2 mg or mg per day [ ] Other:

[ ] Hydrocortisone 5 mg/L Peripheral Soln. [ ] Other:

REPORT TITLE OTSG APPROVED (Date)

ADULT TOTAL PARENTERAL NUTRITION (TPN) & PERIPHERAL PARENTERAL NUTRITION (PPN) ORDER FORM

[ ] [ ] [ ]

STANDARD CENTRAL

Very concentrated solution for the average

patient with perioperative needs (has no free

water).

(AMOUNT/LITER) (AMOUNT/LITER)

STANDARD PERIPHERAL

Limited time use via

peripheral vein while

NPO/advancing

enteral nutrition or in

perioperative status

Dextrose cal 663 (66%) 195 (39%)

Fat cal 342 (34%) 324 (61%)

Sodium chloride 15 mEq 15 mEq

Sodium acetate 35 mEq 35 mEq

Potassium acetate 0 mEq 0 mEq

Magnesium sulfate 8 mEq 8 mEq

Sodium phosphate 0 mM 0 mM

Potassium phosphate 12 mM 8 mM

[ ] LITERS/DAY

PROTEIN 46 gm 30 gm

PROTEIN SOURCE Travasol 10% Travasol 10%

DEXTROSE 195 gm 55 gm

FAT 38 gm 35 gm

CALORIES 1,005 cal 520 cal

[ ] LITERS/DAY

Calcium gluconate 4.8 mEq 4.8 mEq

Potassium chloride 20 mEq 20 mEq

‘INDIVIDUALIZED CENTRAL/PERIPHERAL’

For patients not able to tolerate any of the

standard formulations

(Indicate Amount/Day)

DEXTROSE gm

FAT gm

CALORIES cal

Sodium chloride mEq (30 mEq)

Sodium acetate mEq (70 mEq)

Potassium acetate mEq (0 mEq)

Magnesium sulfate mEq (16 mEq)

Sodium phosphate mM (0 mM)

Potassium phosphate mM (24 mM)

Calcium gluconate mEq (9.6 mEq)

Potassium chloride mEq (40 mEq)

PROTEIN gm

PROTEIN SOURCE [ ] FreAmine HBC 6.9%

[ ] Travasol 10%

[ ] Hepatamine 8% Suggested

Initial

Amounts

[ ] MINIMAL VOLUME OR [ ] LITERS/DAY

Give: [ ] CENTRALLY OR [ ] PERIPHERALLY

per Day:

Ht: cm/in

Ward:

Age: yr

Wt: kg/lb

* Above option requires physician determine

amounts and volume needed per day and route of

administration.

* All orders must reach 4th floor pharmacy by 1300

hours.

* Above standard solutions help expedite initiation of TPN/PPN.

* Determine protein and calorie needs using guidelines page,

select solution and indicate # liters which is closest to patient’s

needs.

(Continues on reverse)

PREPARED BY (Signature & Title) DEPARTMENT/SERVICE/CLINIC DATE

NUTRITION SUPPORT SERVICE

PATIENT’S IDENTIFICATION (For typed or written entries give: Name—

last, first, middle; grade; date; hospital or medical facility) HISTORY/PHYSICAL FLOW CHART

OTHER EXAMINATION

OR EVALUATION

DIAGNOSTIC STUDIES

TREATMENT

OTHER (Specify)

DA 4700 FORM

1 MAY 78

Fig. 23-10. The standard forms used when ordering parenteral nutrition at Walter Reed Army Medical

Center, Washington, DC.

WRAMC OVERPRINT 257

1 NOV 91
Metabolic Derangements and Nutritional Support

569

1. DAILY NON-PROTEIN CALORIE (NPC) GUIDELINES: Give: 25–35 Non-Protein Calories /kg of body weight.

Most patients: 25–30 Cal/kg (30% from Fat) Hypermetabolic/hypercatabolic patients: 30–35 cal/kg (up to 50% from Fat)

1 gm Dextrose = 3.4 Cal 1 gm Fat = 9 Cal Avoid giving > 5 mg Dextrose/kg/min or > 2 gm Fat/kg/day

gm Dextrose needed: cal/kg X kg X ÷ 3.4 =

[desired total cal/kg] [patient’s wt.] [% desired Dextrose cal] [gm DEXTROSE/DAY]

GM Fat needed: cal/kg X kg X % ÷ 9 =

[desired total cal/kg] [patient’s wt.] [% desired Fat cal] [gm FAT/DAY]

OR USE

Energy expenditure = The Harris Benedict Equation X Stress Factor X Activity Factor

MALES = [66 + (13.7 X wt in kg) + (5 X ht in cm) – (6.8 X age)] X ( SF) X ( AF)

FEMALES = [655 + (9.7 X wt in kg) + (1.8 X ht in cm) – (4.7 X age)] X ( SF) X ( AF)

Fig. 23-10 (continued)

ADULT PARENTERAL NUTRITION GUIDELINES

(Central vein total parenteral nutrition (TPN) and Peripheral vein parenteral nutrition (PPN)

ADMINISTRATIVE INFORMATION

*The Standard Formulas specified on the order sheet meet

the requirements of the vast majority of patients who do not

have significant renal/liver dysfunction.

*Peripheral Solutions (PPN) are initiated full volume on the

first day.

*One-half of the amount of Central TPN ordered is normally

sent on 1st day.

*Pharmacy sends one 24 hr solution bag at 2000 hr.

*Orders must be in the 4th Floor Pharmacy by 1300 hr.

*The last TPN bag is used to discontinue TPN.

*For assistance call Pharmacy (1421/22), or page: Nutrition

Support Pharmacist (#1352), Dietitian (#580), Nurse (#272 or

#697), or Physician (#1654).

Stress Factor (SF): Activity Factor (AF)

1.0 to 1.3 (maintenance) Up to 1.5 (for weight gain) Non-ambulatory patient = 1.2

Ambulatory patient = 1.3

PERIPHERAL NUTRITION SOLUTIONS:

Dextrose: 50–60 gm/Liter (Should provide not less than 150 gm/day)

Fat: 50–62% of cal from Fat Osmolarity should be < 800 5 mg of Hydrocortisone/Liter helps reduce phlebitis

Approximately osmolarity (mOsm) of a PPN solution = 50 X final % of protein + 100 X final % of dextrose + 150

2. DAILY PROTEIN GUIDELINES:

gm/kg X kg =

Total Protein needs: [No. of gm/kg] [patient’s wt] [gm PROTEIN/DAY]

Most patients need: 1 – 1.4 gm/kg (via Central or Peripheral vein)

Hypermetabolic/hypercatabolic patients need: 1.5 – 2 gm/kg

Non-dialyzed renal failure patients need: 0.8 – 1 gm/kg

Dialyzed renal failure patients need: 1.0 – 1.5 gm/kg

3. AMINO ACID SOLUTIONS: per 100 mL Essential Branch Chain mEq mEq mEq mM

Have: Protein Amino Acids Amino Acids Sodium Chloride Acetate Phosphate

Travasol 10%: A general purpose 10 gm 45.3% 19% 0 4 8.7 0

amino acid

FreAmine HBC 6.9%: For severely 6.1 gm 66.7% 45% 1 0 5.7 0

compromised patients

Hepatamine 8%: For hepatic 8 gm 55% 36% 1 0 6.2 1

encephalopathy patients

WRAMC OVERPRINT 257

1 NOV 91
Anesthesia and Perioperative Care of the Combat Casualty

570

ADULT PARENTERAL NUTRITION GUIDELINES

4. DAILY MACRONUTRIENT GUIDELINES:

Sodium: 60–180 mEq/day, or 40–60 mEq per liter of TPN

Potassium 80–120 mEq/day, or 40–60 mEq per liter of TPN

Chloride: 60–180 mEq/day, or 30–60 mEq per liter of TPN

Magnesium: 12–30 mEq/day, or 8–12 mEq per liter of TPN (0.3–0.45 mEq/kg)

Calcium: 5–15 mEq/day, or 2–5 mEq per liter of TPN (0.2–0.3 mEq/kg)

Phosphorus: 10–15 mM /1,000 cal, or approximately: 8–12 mM per liter of TPN

Note: 3 mM of K Phosphate has 4.4 mEq K, and 3 mM of Na Phosphate has 4 mEq Na

Acetate: Balances cations and anions, adjusts acid-base balance of the solution. One mEq of Acetate through

intermediary metabolism equates to administration of 1 mEq of Bicarbonate

5. DAILY MICRONUTRIENT GUIDELINES:

Daily dose 4 mL, reduce by 50% in non-dialysis renal failure patients

METAL IV DAILY ADULT DOSE MULTI-TRACE-5 /4mL

Zinc: *2.5–4.0 mg 4.0 mg

Copper: 0.5–1.5 mg 1.6 mg

Manganese: 0.15–0.8 mg 0.4 mg

Chromium: 10.0–15.0 mcg 16.0 mcg

Selenium: 20.0–60.0 mcg 80.0 mcg

* An additional 2 mg per day is suggested for highly catabolic states

* Significant G.I. fluid loss requires an additional 12 mg Zinc/L of TPN

6. DAILY FLUID GUIDELINES:

Normal TPN patient requires approximately 1 mL per cal

7. DAILY ADULT MULTIPLE VITAMINS:

Provide a minimum of 10 mL/day

10 mg of Vitamin K should be given intramuscularly q Monday for patients not receiving anticoagulants.

Fig. 23-10 (end)

8. INSULIN IN ADULT PARENTERAL NUTRITION:

If adding insulin to nutrition soln., add a max of 50% of

previous days total insulin usage

9. NUTRITIONAL STATUS INDICATORS:

Degree of malnutrition: Mild Moderate Severe Notes:

Albumin (mg/dL) 3.0–3.5 2.1–3.0 < 2.1 half-life 18 days, affected by hydration status, blood

loss, etc

Transferin (mg/dL) 150–200 100–150 < 100 half-life 8 days, affected by iron deficiency, chronic

infection

Prealbumin (mg/dL) Males: 19–39 mg/dL and Females: 19–30 mg/dL half-life 1.9 days, indicator of catabolism, synthesis,

and liver function. Obtain a baseline value before

initiating TPN/PPN

Steady state nitrogen balance = [nitrogen in (gm protein ÷ 6.25)] – [24 hr Urinary Urea Nitrogen (UUN) in gm + 4 gm]

WRAMC OVERPRINT 257

1 NOV 91

Suggested Insulin Sliding Scale:

Finger Stick: Insulin Dose (q 6 hr)

150–249 mg% 2 Units Reg. Human Insulin

250–300 mg% 4 Units Reg. Human Insulin

301–350 mg% 6 Units Reg. Human Insulin

351–400 mg% 8 Units Reg. Human Insulin

> 401 mg% draw STAT Serum Glucose and NOTIFY PHYSICIAN
Metabolic Derangements and Nutritional Support

571

while to realize that these patients were already

phosphorus depleted, and had adjusted to a lowcalorie, low-protein diet. Feeding with a highcalorie, high-protein diet consumed what phosphate

they had left: ATP levels fell; 2,3-diphosphoglycerate

levels fell; red blood cells could no longer unload

oxygen; glucose-dependent organs could no longer

effectively uptake glucose; and the patients died.

Thirty years later, phosphate depletion was rediscovered when critically ill, catabolic patients were

placed on TPN before the vital role of phosphorus

was appreciated.38,39

Increased amounts of phosphorus are lost in the

urine after trauma and sepsis, and even after routine surgery. Levels decrease further with early

postoperative feeding, as glucose enters cells as

glucose-6-phosphate, and as ATP levels fall in hypercatabolism. Phosphorus is the major intracellular anion; the normal intracellular concentration of

phosphorus is 75 mEq/L. The plasma concentration is far less, 1.0 to 1.5 mEq/L, or 2.3 to 4.5 mg/dL

(or 1–1.4 mmol/L; there is considerable lack of

consistency in reporting results with this anion).

An extracellular phosphorus level of less than 1.0

to 1.2 mg/dL will cause respiratory weakness and

usually cardiac arrest when it reaches 0.8 μg. Intravascular hemolysis, white blood cell and platelet

dysfunction, myocardial dysfunction, and central

nervous system dysfunction (including ataxia, seizures, and coma) all result from phosphorus depletion. Unfortunately, the serum phosphate levels do

not accurately reflect intracellular depletion and

are not a perfect guide for replacement. In addition,

the phosphorus content of lipid solutions, or of

phosphate in lipid solutions, may not be bioavailable, and the replacement therefore is less than

predicted.

The phosphorus content of salts (sodium or potassium) is expressed in millimoles: 15 mmol of

potassium phosphate provides 15 mmol of phosphate. The cations in the salt are, however, expressed as milliequivalents: 15 mmol of potassium

contains 22 mEq of potassium. The fact that the

cation and phosphate have different valences must

be borne in mind when replacing phosphorus. Generally, 15 to 30 mmol of the salt per day mixed with

the TPN provides adequate maintenance phosphorus. Sodium or potassium phosphate may be given

as a piggyback intravenous infusion, at a rate of 15

to 30 mmol over 2 to 4 hours. Infusion rates more

rapid than this may cause intravenous precipitation

of calcium phosphate and hypocalcemia, and, if

potassium phosphate is used, hyperkalemia.

Trace Elements

Trace elements are the catalysts and cofactors

that drive the cellular machinery; defects in these

impair protein synthesis and cellular energetics.

More than nine elements are considered essential,

but deficiencies in only five are likely to present problems in the intensive care setting (see Figure 23-10).

Little is known of the changes that levels of these

undergo in metabolic stress due to trauma or sepsis.

Iron is one trace element that is generally not

replaced.27 Inflammation, fever, and intravascular

endotoxin are associated with a fall in serum iron

levels. Lactoferrin and transferrin both bind iron

when release of inflammatory mediators occurs,

activating granulocytes. This binding of iron is

essential for normal immune function, at least partly

because the body makes iron unavailable to invading bacteria.40 Peritoneal or retroperitoneal blood,

intravascular hemolysis, and other conditions that

make hemoglobin available to bacteria are all associated with an increased incidence of sepsis.

More than 200 enzymes essential to metabolic

function depend on the availability of zinc. Carbohydrate, lipid, protein, and nucleic acid metabolism all depend on an adequate level of zinc, although “adequate” may be difficult to define in the

critically ill. Inadequate amounts of tissue and

plasma zinc can impair normal wound healing,

platelet aggregation, neutrophil chemotaxis, and

transformation of lymphocytes. Obvious signs of

deficiency (eg, poor appetite, malabsorption with

diarrhea, mental depression) are not uncommon in

the critically ill, and not specific. The scaly, hyperpigmented dermatitis may be a late finding and

may be misdiagnosed. Normal oral zinc intake is 10

to 20 mg/d, of which 20% to 30% is absorbed.

Normal losses are 0.5 mg/d in urine, at least 0.5

mg/d in perspiration, and 2 to 3 mg/d in the gastrointestinal tract. Loss of zinc accelerates in bowel

disorders, as absorption depends on intact

enterocytes; malabsorption, inflammatory bowel

disease, massive small-bowel resection, and

pancreatitis all are associated with higher losses

and decreased absorption. Alcohol abuse and

chronic (or massive) diuretic use also accelerate

zinc loss, and patients may present with already

low or low-normal zinc stores. Patients with burns

and acute renal failure also show increased zinc

loss. Urinary zinc losses increase in critical illness,

in association with the increased nitrogen losses,

and IL-1 release causes a rapid decline in serum

zinc as the liver takes up large amounts of the
Anesthesia and Perioperative Care of the Combat Casualty

572

mineral. Zinc accumulates in the liver as

metallothionein, which is used to produce α2-macroglobulin, a protease inhibitor, as a check on the

inflammatory reaction. The maintenance dose of

zinc is 2 to 4 mg/d added to the TPN solution. In

patients who are highly stressed or catabolic or

both, however, an additional 2 mg/d should be

added. There is some suggestion41 that nitrogen

balance may improve with zinc repletion.

Copper is another mineral that is depleted by

bowel disorders. Short-bowel syndrome, jejunoileal

bypass, malabsorption, enterocutaneous fistulae,

and biliary obstruction all lose copper. An increased hepatic synthesis of ceruloplasmin in infection or inflammatory states, mediated by IL-1,

acutely drops serum copper levels. Prolonged administration of zinc, because of the increase in

metallothionein, also lowers copper levels. Copper

is required for the normal function of cytochrome

oxidase and superoxide dismutase, two vital enzyme systems in our patient population. Normal

daily replacement dose is 0.5 to 1.5 mg/d.

Manganese is also required for a number of enzyme reactions, and is generally added to trace

element formulas. This element should be avoided

in biliary obstruction.

Chromium improves glucose tolerance in the

critically ill and allows maximum enhancement of

the initial reaction of insulin with its receptor.

Adding chromium has little effect on glucose tolerance in patients who are not chromium deficient,

but improves it in those who are. Chromium, like

zinc, decreases in acute renal failure.

Selenium is required at the catalytic site of glutathione reductase. Its role is to help reduce organic

hydroperoxides and lipoperoxides resulting from

stress, sepsis, and ischemia. Selenium deficiency

impairs immune function by (a) impairing the ability of granulocytes to kill bacteria and (b) damaging

granulocytes by the excess accumulation of hydrogen peroxide, which damages the free radical–generating system in those cells. The functioning of T

helper cells is also impaired by selenium deficiency.

In the lungs, glutathione reductase scavenges oxygen-derived free radicals, offering some protection

against damage from these radicals, particularly in

patients who require high FIO2. Selenium is excreted renally, and is also lost in burn and wound

exudates, bowel fluids, and enterostomy fluids or

enterocutaneous fistulae. The daily requirement is

20.0 to 60.0 μg. Higher doses are generally required

for higher stress states; however, ingestion of more

than 1 mg/d may cause toxicity. Replacement of 50

to 200 μg/d is considered adequate.

Vitamins

Vitamins are small, organic molecules that are

needed in tiny amounts for the normal function of

metabolic processes. In general, the metabolic machinery needed for their synthesis is lacking in

humans, and a prolonged, deficient intake of a

given vitamin will ultimately result in a characteristic and sometimes dramatic clinical syndrome such

as scurvy due to a lack of ascorbic acid (vitamin C)

and beriberi due to a lack of thiamine (vitamin B1).

Members of the U.S. military who are deployed to a

combat zone are most unlikely to manifest evidence

of vitamin deficiencies. However, some degree of

vitamin intake is indicated. Without any intake,

body stores of water-soluble vitamins (C and the B

group) will disappear within 4 to 5 months.42 Fortunately, data from the Ranger Training Study indicate that consumption of the U.S. Army’s meals

ready to eat (MREs) maintained normal serum levels of vitamins A, C, B1, B6, and B12 over a 2-month

period.8(Fig 20, Fig 21)

Nevertheless, the normal daily requirement of

certain vitamins (eg, vitamins A, certain members

of the B group, and especially C) may be increased

by as much as 3- to 10-fold in the severely injured.43

In addition, vitamin supplementations have subtle

effects that may possibly be beneficial, such as the

increased mobility of polymorphonuclear neutrophils in trauma patients brought about by high

doses of either α-tocopherol or vitamin C.44 Recommended vitamin doses are given in Table 23-3.

Care should be taken to prevent overdosing,

especially when administering fat-soluble vitamins

such as A and D. Large doses—10-fold greater than

the recommended dietary allowances—of the water-soluble vitamins such the B complex and C appear not to be associated with toxicity.

Both fat- and water-soluble vitamins must be

regularly replaced during TPN. Commercial preparations are usually available, and one 10-mL ampule per day of a multivitamin mix added to the

TPN will suffice. Vitamin K, 10 μg/wk, should be

given intravenously, but slowly.

Delivery of Total Parenteral Nutrition

TPN should be thought of as “preenteral” feeding. It lacks the gut stimulation necessary to decrease bacterial translocation and preserve mucosal

structure, but it is often the only way to feed a

patient. TPN requires a dedicated line. This means

that nothing else goes through that line, not even a

little (including withdrawing blood at 3 AM). When
Metabolic Derangements and Nutritional Support

573

TABLE 23-3

VITAMIN REQUIREMENTS

Amount Daily Amount

RDA Daily, for the Daily, for Provided Provided by

for Daily Moderately the Severely by One Standard IV

Vitamin Units Oral Intake1 Injured Injured Vitamin Pill Preparations2

Vitamin A (retinol) IU 1,760 5,000 5,000 10,000 3,000

(females) (retinal)

3,300

(males)

Vitamin D (ergocalciferol) IU 200 400 400 400 200

Vitamin E (tocopherol) mg TE 8–10 unknown unknown 15 10 IU*

Vitamin K (phylloquinone) μg 20–40† 20 20 0 0‡

Vitamin C (ascorbic acid) mg 60 75 300 100 100

Thiamine (vitamin B1) mg 1.0–1.5 2 10 10 3.0

Riboflavin (vitamin B2) mg 1.2–1.7 2 10 10 3.6

Niacin mg 13–19 20 100 100 40

Pyridoxine (vitamin B6) mg 2.0–2.2 2 40 5 4

Pantothenic acid mg 4–7 18 40 20 15

(adults)

Folic acid mg 0.4 1.5 2.5 0 0.4

Vitamin B12 (cobalamin) μg 3.0 2 4 5 5

Biotin μg 100–200† unknown unknown 0 60

*Equivalent to RDA

†Estimated to be safe and adequate dietary intakes

‡Must be supplemented in peripheral venous solutions

IU: international units; RDA: recommended dietary allowance; TE: α-tocopherol equivalent; IV: intravenous

Sources for these values: (1) Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, DC: National Academy

of Sciences, National Academy Press; 1990. (2) Nutrition Advisory Group. Multivitamin preparations for parenteral use: A statement

by the Nutrition Advisory Group, American Medical Association Department of Foods and Nutrition, 1975. JPEN. 1979;3:258.

Reprinted with permission from Rombeau JL, Rolandelli RH, Wilmore DW. Nutritional support. Chap 10. In: Part 2. Care in the ICU.

In: Wilmore DW, Brennan MF, Harken AH, Holcroft JW, Meakins JM, eds. Vol 1. Critical Care. In: Care of the Surgical Patient. New York,

NY: Scientific American, Inc; 1988: 10-6.

protocol is violated, lines become infected. Strict

asepsis—cap, mask, gloves, and sterile gown—is

required to insert and care for the intravenous line.

Insertion is into the subclavian vein where possible,

using a modified Seldinger technique (Figure 23-11).

A TPN line may also be inserted using the internal jugular vein or the femoral vein. These sites

have slightly higher rates of infection, but as long as

no gross soiling of the catheter is probable and strict

aseptic technique is used, any difference in infection rate will be minimal. The antecubital fossa

veins should be avoided for a number of reasons,

among them a high rate of infection.

Single-lumen catheters may be used but are often

impractical in the intensive care unit. Most intensive care specialists favor using a triple-lumen catheter, with one port dedicated to TPN. As another

alternative, a dedicated infusion port—not the central venous pressure port and under no circumstances

the pacing port of a Paceport pulmonary artery

catheter (manufactured by Edwards/Baxter, Irvine,

Calif.), which opens directly into the right ventricle—may be used, with the same protocol as for a

single or multilumen central line. The position of

the catheter must be verified by chest X-ray examination prior to infusion of TPN. Relative contra-
Anesthesia and Perioperative Care of the Combat Casualty

574

Fig. 23-11. The subclavian approach to central venous

catheterization. The patient is placed in Trendelenburg’s

position to allow filling and dilation of the subclavian

vein (a). The shoulders are thrown back maximally (a

small sheet roll may even be placed beneath the spinal

column), and the head is rotated to the side opposite the

insertion site. The upper chest and neck are prepared and

draped using aseptic technique (the operator should

wear hat, mask, gown, and gloves). Local anesthetic is

infiltrated into the skin and underlying tissue along the

inferior border of the clavicle at or slightly lateral to its

midpoint. The needle found in a standard subclavian catheter insertion kit is attached to a syringe and advanced

through the anesthetized area parallel to and beneath the

clavicle, but over the first rib. The tip of the needle is

aimed at a fingertip pressed firmly into the suprasternal

notch. With the needle shaft parallel to the frontal plane

of the patient (ie, parallel to the bed), the needle will enter

the subclavian vein after advancing about 1.5 to 2.0 in.

beneath the skin. Slight negative pressure applied to the

syringe will allow the prompt inflow of blood when the

vein is entered. The needle is advanced a few millimeters

after venous blood is obtained to ensure that the entire

beveled tip is within the vein lumen.

As the patient performs the Valsalva maneuver to

prevent air embolism, the syringe is removed and the

guide wire inserted (b). The wire should advance into the

venous system without resistance or pain to the patient.

After at least one half of the wire has been advanced into

the vein, the needle is removed over the guide wire (c). A

small incision is made at the entrance site into the skin,

and a dilator is passed over the wire and into the soft

tissue (d). In a well-muscled person, some resistance may

be met; the fascia is best traversed by using a screwlike

motion and firm, constant pressure on the dilator. As the

dilator is advanced, the wire should always remain freely

movable within the dilator’s lumen. The dilator is then

removed over the wire and replaced by the catheter, an

approximate length of which is advanced over the wire

into the patient (e). This length can be approximated

before insertion by measuring the distance between the

insertion site and the point on the sternum at the level of

the second intercostal space. The wire is then removed,

and the catheter lumen is aspirated free of all air and

flushed with saline. The catheter is sutured into position

(f), the exit site cleaned, and a dressing applied. Reprinted with permission from Rombeau JL, Rolandelli

RH, Wilmore DW. Nutritional support. Chap 10. In: Part

2. Care in the ICU. In: Wilmore DW, Brennan MF, Harken

AH, Holcroft JW, Meakins JM, eds. Vol 1. Critical Care. In:

Care of the Surgical Patient. New York, NY: Scientific American, Inc; 1988: 10-15.

b

c

d

e

f

a
Metabolic Derangements and Nutritional Support

575

indications are those for insertion of any central

line: high intrathoracic pressures, platelets less than

50,000, prolonged bleeding time, or elevated prothrombin time/partial thromboplastin time. Under

these circumstances, the femoral vein or a surgical

cutdown should be considered.

The question of how often to change intravenous

TPN lines is controversial. At Walter Reed Army

Medical Center, if proper technique is used, we find

little difference in infection rates—whether the lines

are changed every 3 days or every 5 days. Doublegloving or double-operator techniques give equally

low colonization and infection rates regardless of

whether the line change is performed over the wire

or the catheter is removed to a new location. We use

over-the-wire changes every 5 days and culture all

catheter tips. We change to a new site only if a line

tip is colonized (> 15 colonies). Line dressings are

aseptically changed daily. While the practice of

leaving lines in until the site is inflamed may have

a low incidence of infection under normal peacetime conditions on hospital wards, during wartime,

patient care in intensive care units will require

regular changes of all central lines, with culture of

all catheter tips whenever possible.

At a minimum, glucose and electrolytes must be

monitored daily. In unstable or highly catabolic

patients, electrolytes, and especially glucose, must

be followed more closely, occasionally as often as

every 3 hours. Protein, glucose, lipids (therefore

total calories), and electrolytes must be reviewed

and adjusted daily to fit the needs of the patient. If

insulin or potassium requirements grow out of proportion to caloric load or normal daily losses, it is

far better to use a baseline amount in the TPN and

give additional amounts of hormone or electrolyte

as a separate intravenous infusion, than it is to alter

the TPN mixture continually.

Complications of Total Parenteral Nutrition

Complications of parenteral feeding may be

grouped into three categories: (1) injury to contiguous anatomical structures during catheter insertion, (2) catheter-related sepsis, and (3) metabolic

complications caused by parenteral nutrition. The

likelihood of catheter-related complications such as

pneumothorax and laceration of vessels in the root

of the neck is, to a high degree, determined by the

experience of the practitioner and meticulous attention to detail during catheter insertion. Expertise in

inserting central lines is the essential prerequisite

for a low incidence of iatrogenic injuries.

Measures to minimize sepsis arising from a

parenteral line depend primarily on the adequacy

of nursing care. An excerpt from the Infection Control Policy and Procedure Guide developed at Walter

Reed Army Medical Center in 1991 is reprinted at

the end of this chapter for the benefit of interested

readers. The complexity of the control measures

serves to remind us why parenteral nutrition is not

always feasible in the field echelons of care.

A multitude of metabolic derangements occur

during parenteral nutrition. For the sake of completeness, they are listed in Table 23-4, although

many are not likely to occur in combat casualties

receiving parenteral nutrition. It should be noted

that the diagnosis of metabolic complications is somewhat dependent on the availability of an extensive

array of laboratory tests, not all of which will be

available in deployable medical facilities. Among

the more common metabolic derangements are

• hyperglycemia due to too-rapid infusion of

glucose, which, if not corrected, can give

rise to hyperosmotic nonketotic coma; and

• hypoglycemia due to excessive endogenous

or exogenous insulin.

Modifications of Total Parenteral Nutrition

Certain preexisting medical conditions such as

renal, hepatic, and respiratory failure are known to

complicate the application of parenteral nutrition.

Experience has shown us that modifications in standard protocols for parenteral nutrition are indicated whenever these conditions are present.

Modifications for Renal Failure. Acute renal

failure prevents the excretion of the end products of

nitrogen metabolism. Urea accumulates from both

dietary proteins and endogenous protein catabolism, the measured BUN representing the balance

between the increased urea production and the

limited ability of the kidney to excrete nitrogenous

wastes. Gastrointestinal bleeding and reabsorption

of blood nitrogen can markedly elevate BUN in a

short time, and this situation is not uncommon in

the critically ill.

Protein intake can be decreased in renal failure

by reducing exogenously provided amino acids and

by providing amino acids of high biological value

(Table 23-5). Protein should be reduced to 0.5 g/

kg/d when the BUN reaches 60 to 80. Additional

carbohydrate calories are supplied, to allow utilization of the elevated nitrogen pool as well as to take

advantage of the relative protein sparing provided
Anesthesia and Perioperative Care of the Combat Casualty

576

TABLE 23-4

METABOLIC COMPLICATIONS OF TOTAL PARENTERAL NUTRITION

Problems Possible Causes Corrective Measures

SGOT: serum glutamic-oxaloacetic transaminase; SGPT: serum glutamic-pyruvic transaminase

Reprinted with permission from Rombeau JL, Rolandelli RH, Wilmore DW. Nutritional support. Chap 10. In: Part 2. Care in the ICU. In: Wilmore DW, Brennan

MF, Harken AH, Holcroft JW, Meakins JM, eds. Vol 1. Critical Care. In: Care of the Surgical Patient. New York, NY: Scientific American, Inc; 1988: 10-23.

Glucose

Hyperglycemia, glycosuria osmotic, Excessive total dose or rate of infusion of glucose; Reduce amount of glucose infused;

diuresis, hyperosmolar nonketotic inadequate endogenous insulin; increased increase insulin; administer a

dehydration and coma glucocorticoids; sepsis portion of calories as fat emulsion

Ketoacidosis in diabetes Inadequate endogenous insulin response; Give insulin; reduce glucose input

inadequate exogenous insulin therapy

Postinfusion (rebound) hypoglycemia Persistence of endogenous insulin production Administer 5%–10% glucose before

secondary to prolonged stimulation of islet cells by infusion is discontinued

high-carbohydrate infusion

Fat

Pyrogenic reaction Fat emulsion, other solutions Exclude other causes of fever

Altered coagulation Hyperlipidemia Restudy after fat has cleared bloodstream

Hypertriglyceridemia Rapid infusion, decreased clearance Decrease rate of infusion; allow

clearance before blood tests

Impaired liver function test results May be caused by fat emulsion or by an underlying Exclude other causes of hepatic

disease process dysfunction

Cyanosis Altered pulmonary diffusion capacity Discontinue fat infusion

Essential fatty acid deficiency Inadequate essential fatty acid administration Administer essential fatty acids in the form

of one 500-mL bottle of fat emulsion every

2–3 d

Amino Acids

Hyperchloremic metabolic acidosis Excessive chloride and monohydrochloride content Administer Na+ and K+ as acetate salts

of crystalline amino acid solutions

Serum amino acid imbalance Unphysiological amino acid profile of the nutrient Use experimental solutions if indicated

solution; differential amino acid utilization with

various disorders

Hyperammonemia Excessive ammonia in protein hydrolysate solutions; Reduce amino acid intake

deficiency of arginine, ornithine, aspartic acid, or

glutamic acid, or a combination of these deficiencies

in amino acid solutions; primary hepatic disorder

Prerenal azotemia Excessive amino acid infusion with inadequate Reduce amino acid intake;calorie increase

administration glucose calories

Calcium and Phosphorus

Hypophosphatemia Inadequate calcium administration; reciprocal Administer phosphorus (> 20 mEq

response to phosphorus repletion without potassium dihydrogen phosphate/1,000

simultaneous calcium infusion; hypoalbuminemia IV calories); evaluate antacid or calcium

administration or both

Hypocalcemia Inadequate calcium administration; reciprocal Administer calcium

response to phosphorus repletion without simultaneous calcium infusion; hypoalbuminemia

Hypercalcemia Excessive calcium administration with or without high Decrease calcium or vitamin D

doses of albumin; excessive vitamin D administration

Vitamin D deficiency; Inadequate or excessive vitamin D Alter vitamin D administration

hypervitaminosis D

Miscellaneous

Hypokalemia Potassium intake inadequate relative to increased Alter nutrient administration

requirements for protein anabolism; diuresis

Hyperkalemia Excessive potassium administration, especially in Alter nutrient administration

metabolic acidosis; renal failure

Hypomagnesemia Inadequate magnesium administration relative to Alter nutrient administration

increased requirements for protein anabolism and

glucose metabolism; diuresis; cisplatin administration

Hypermagnesemia Excessive magnesium administration; renal failure Alter nutrient administration

Anemia Iron deficiency; folic acid deficiency; vitamin B12 Alter nutrient administration

deficiency; copper deficiency; other deficiencies

Bleeding Vitamin K deficiency Alter nutrient administration

Hypervitaminosis A Excessive vitamin A administration Alter nutrient administration

Elevations in SGOT, SGPT, and serum Enzyme induction secondary to amino acid imbalance Reevaluate status of patient

alkaline phosphatase or to excessive deposition of glycogen or fat, or both,

in the liver
Metabolic Derangements and Nutritional Support

577

TABLE 23-5

COMPOSITION OF AMINO ACID SOLUTIONS FOR PATIENTS WITH RENAL FAILURE

BUN 40–60 mg/dL BUN 60–80 mg/dL BUN 80–100 mg/dL

Moderate High Moderate High Moderate High

Calories Calories Calories Calories Calories Calories

Volume

Amino acids (mL) 500 (mixture 500 (mixture 250 (mixture 250 (mixture 400 (essential 400 (essential

high in essential high in essential high in essential high in essential amino acids amino acids

amino acids*) amino acids*) amino acids*) amino acids*) only) only)

Dextrose (mL) 500 (50%) 500 (70%) 500 (50%) 500 (70%) 500 (50%) 500 (70%)

Total (mL) 1,000 1,000 750 750 900 900

Contents

Amino acids (g) 32.5 (3.2%) 32.5 (3.2%) 16.3 (2.1%) 16.3 (2.1%) 20.8 (2.3%) 20.8 (2.3%)

Dextrose (g) 250 (25%) 350 (35%) 250 (33%) 350 (47%) 250 (28%) 350 (39%)

Total nitrogen (g) 5 5 2.5 2.5 3.3 3.3

Nonprotein 170 238 340 476 258 360

kcal/g N

Total kcal 875 1,315 913 1,253 932 1,273

kcal/mL 0.9 1.3 1.2 1.7 1.0 1.4

*70% essential amino acids and 30% nonessential amino acids

Reprinted with permission from Rombeau JL, Rolandelli RH, Wilmore DW. Nutritional support. Chap 10. In: Part 2. Care in the ICU.

In: Wilmore DW, Brennan MF, Harken AH, Holcroft JW, Meakins JM, eds. Vol 1. Critical Care. In: Care of the Surgical Patient. New York,

NY: Scientific American, Inc; 1988: 10-18.

volume, protein, and fat that patients with renal failure who are not undergoing dialysis receive. Volume

is generally liberalized to 2 to 2.5 L/d in patients

undergoing dialysis. In noncatabolic patients, protein

requirements are 1.0 to 1.5 g/kg/d. Higher protein intake will be required in patients who remain catabolic

or are on CAVH or CAVH-D. Caloric requirements

also increase for hemodialysis patients and those on

CAVH. Patients receiving CAVH-D, however, absorb

some glucose from the countercurrent dialysate solution, and caloric input from TPN is often reduced

slightly to compensate. In patients on hemodialysis or

CAVH-D, folate and the B vitamins must be replaced

in greater-than-normal amounts. Increased replacement should be considered in patients in the diuretic

phase of acute tubular necrosis, as well.

This late phase of acute tubular necrosis is often

marked by hypokalemia and hypomagnesemia, as

these electrolytes “wash out” while sodium is, relatively, retained. Close monitoring of electrolytes

and frequent adjustments to TPN and maintenance

fluids are required during this period.

Modifications for Hepatic Failure. The nutritional requirements in severe hepatic dysfunction

or hepatic failure depend primarily on the primary

disease or trauma, rather than on the hepatic failure

by an increased carbohydrate load in the catabolic

patient. Total volume is decreased, to 1 to 1.5 L/d in

the anuric or significantly oliguric patient. Parenteral

formulations must be modified to decrease phosphorus, magnesium, and, usually, potassium. Electrolyte supplementation must be recalculated daily,

based on close monitoring of the patient’s electrolytes, as carbohydrate loading and glucose intolerance will produce electrolyte shifts. Chloride intake

should be reduced, and the acetate salts of sodium and

potassium utilized to a greater extent, to counter the

metabolic acidosis that accompanies uremia. Caloric input from fat is reduced, as fats do not have as

great a protein-sparing effect as do carbohydrates,

and fats contain 15 mmol of phosphate per liter.

Trace elements should be decreased, or withheld

for 1 to 2 weeks, unless the patient requires dialysis.

If the BUN rises to the 80 to 100 range or above,

replacing the standard amino acid mixture with a

specialized renal failure formulation is justified.

These renal failure–specific formulations generally

have a higher proportion of essential amino acids.

Patients receiving hemodialysis regularly, or those

on continuous arteriovenous hemofiltration (CAVH)

or continuous arteriovenous hemodiafiltration

(CAVH-D), will not need the severe restrictions in
Anesthesia and Perioperative Care of the Combat Casualty

578

per se. The only exception is acute, fulminant

hepatitis, where metabolic demands on the liver

must be severely restricted. Protein is often limited

in hepatic encephalopathy, but has not been shown

to alter outcome in severe hepatic dysfunction or

multiorgan failure. Similarly, formulations specific

for hepatic dysfunction or failure or both (ie, those

high in branched-chain amino acids and low in

aromatic amino acids) are often used to offset the

elevated levels of aromatic amino acids found in

hepatic dysfunction. Like protein limitation, these

specific formulations have not effected significant

improvements in outcome, although patients remain responsive longer and are somewhat easier to

manage metabolically. A reasonable strategy is to

provide 1.0 to 1.5 g/kg/d to patients with hepatic

failure, until their ammonia levels rise to the point

where the encephalopathy worsens, and then to

switch to a formula low in aromatic amino acids and

high in branched-chain amino acids.

Hepatic failure formulations generally contain

no trace elements (see the hepatic amino acid section of Figure 23-10). These must be individually

added, based on the needs of the particular patient.

Nearly all critically ill patients will require the

addition of zinc, but certain trace elements may

actually be harmful. Copper, in particular, is best

avoided in patients with hepatic failure. Folate and

the B vitamins must be supplemented in these patients, as they must also in patients with renal failure.

Modifications for Respiratory Failure. Modification of TPN for patients with respiratory failure is

somewhat easier. Glucose is oxidized to carbon

dioxide and excreted via the lungs. Since the rate of

gas exchange is altered by the administration of

carbohydrate, changes in minute ventilation requirements with feeding should be noted. Patients with

inadequate pulmonary reserve, or with a fixed rate

of carbon dioxide excretion (ie, those on mechanical

ventilation) are particularly susceptible, as they

cannot vary the rate of gas exchange with feeding.

While overfeeding calories should be avoided in all

patients, those with respiratory insufficiency are

particularly sensitive to carbohydrate calories. Fortunately, probably fewer than 10% of mechanically

ventilated patients need modification of standard

nutritional formulae. In those few who do, a 50:50

division of calories between carbohydrate and fat,

with 1 g of protein per kilogram of body weight per

day and a 150:1 ratio of calories to nitrogen, is

usually adequate. If this is unsuccessful in allowing

the patient to wean from the ventilator, a reduction

in total calories to 60% to 70% of calculated requirements may be tried briefly.

Peripheral Parenteral Nutrition

Inpatients who do not require complete nutritional

support but who need a brief period of supplementation, peripheral parenteral nutrition (PPN) may be

used. The most significant advantage of PPN is that a

peripheral intravenous catheter—albeit a dedicated,

single-purpose line—may be used instead of a central

catheter. The feeding is necessarily of lower caloric

density, generally 0.3 to 0.6 kcal/mL, but 1,200 to

2,300 kcal can be delivered daily.

The singular disadvantage of PPN is that it requires a large volume of fluid, often 2 to 4 L/d. The

fluid has an osmolarity between 600 and 800 mOsm/L

and should not be given peripherally if greater than

800 mOsm/L. Osmolarity can be approximated as

follows:

(50 • % protein in final mix)

+ (100 • % glucose in final mix) + 150

Intravenous catheter sites must be changed every 48 to 72 hours, both because of the risk of

infection and because of the irritation that a

hyperosmolar fluid causes in small veins. A small

amount of hydrocortisone (5–10 μg/L) added to the

infusion may help to reduce phlebitis. Fat emulsions are given separately, every day or every other

day, and should provide 50% to 60% of the calories.

Insulin

Insulin may be added to both TPN and PPN,

generally to a maximum of 50% of the insulin used

the previous day. This will never provide—and

should not provide—complete insulin coverage.

Some of the added insulin will be adsorbed onto the

intravenous catheter tubing. Insulin will have to be

supplemented by either an intravenous insulin infusion (often the easiest route of administration to

use in critically ill patients) or by injecting intermittent boluses of insulin according to a sliding scale

(see part 8 of Figure 23-10). An intravenous infusion can be prepared by adding 125 units of insulin

to 250 mL of 5% dextrose in water, running 100 mL

through the tubing to saturate the tubing and prevent further adsorption, and then beginning the infusion at 0.5 to 1.0 unit per hour. The insulin infusion

can be titrated to a blood glucose between 180 and

220 μg/dL. Alternatively, a sliding scale may be

based on glucose determinations from finger sticks,

with laboratory confirmation every 4 hours. Insulin

given according to a sliding scale must be administered subcutaneously because the half-life of regu-
Metabolic Derangements and Nutritional Support

579

lar insulin is too short when given intravenously,

and hourly injections would be required.

Sliding-scale dosages of insulin often must be

adjusted and often have to be imposed on top of a

baseline insulin infusion, particularly in hypercatabolic patients who are refractory to the action of

exogenous insulin.

Enteral Nutrition

Enteral feeding has recently come to be accepted

as the preferred route for providing nutritional

support after trauma or during infection. While

there are often reasons that the parenteral route

must be used, enteral feeding is the more physiological, and provides several advantages. The gut

is an active organ, deeply involved in the processing and regulation of a large number of nutrients,

peptides, inflammatory mediators, hormones, and

immunoglobulins. It is a major component of host

defense against invading microorganisms, both as a

mechanical barrier and as a major immune organ,

especially during periods of stress. During starvation and the catabolic state induced by trauma or

sepsis, the health of the gut relates directly to the

health of the organism.

The cells of the intestinal mucosa, the enterocytes,

are the most rapidly proliferating cells in the body.

Feeding is the primary stimulus—both direct and

indirect—for the growth of these cells. Feeding

directly stimulates desquamation of the gut lining

and enhanced renewal of the enterocytes, while

enteroglucagon, gastrin, and other gut hormones indirectly stimulate cell renewal and growth. The gut,

in turn, regulates circulating nutrients through mechanisms more complex than the simple digestion and

absorption of feedings. Amino acids and glucose

released from catabolized muscle are processed by the

gut before they are transported to the liver. Glutamine,

a “nonessential” amino acid that makes up a large

percentage of the amino acids released from skeletal

muscle during stress, is the principal oxidizable

fuel for the small bowel. Half the glutamine extracted by the small bowel is oxidized to ammonia,

which is, in turn, passed on to the liver for processing to new proteins, and which represents a good

part of total body protein turnover. During the

catabolism that follows trauma or infection, amino

acid uptake by the gut accelerates. This acceleration

is, to some extent, matched by the increased release of

glutamine by catabolized skeletal muscle. During

stress, however, consumption outstrips production,

glutamine concentrations fall, and the small intestine

finally runs short of fuel and substrate.

Mucosal epithelial cells of the colon use glutamine

to a lesser extent. The large bowel depends on

short-chain fatty acids—chiefly butyric, acetic,

and propionic—and keto acids for fuels. The

short-chain fatty acids are vital for sodium and

water reabsorption by the colon and for cell growth

and proliferation. Short-chain fatty acids are produced by bacterial fermentation of polysaccharides.

The gut bacteria use less than 10% of the energy of

the polysaccharides themselves. The rest of the

energy goes to produce large amounts of shortchain fatty acids, with acetate, propionate, and butyrate comprising 83% of the product in a ratio of

1:0.3:0.25. These energy-carrying compounds can

then either be absorbed (> 500 kcal/d in a fed gut)

or excreted.

Release of inflammatory mediators, the use of

antibiotics and histamine type 2 (H2) blocking

agents, and inadequate provision of enteral calories

will each alter the functions and mechanical integrity of the intestine. An intact mucosal barrier and

intact immunological function reduce both transmigration of bacterial endotoxin and translocation

of enteric bacteria. Endotoxin is normally absorbed

across the cell barrier in a controlled fashion and

presented to the Kupffer cells for detoxification.

Production of stress hormones and the normal catabolic response to injury are modulated. Loss of cell

mass because of starvation or increased catabolism

diminishes this normal modulation. Continued

loss of cell mass or the introduction of hypotension

result in cell edema and loss of function, and physically disrupt the barrier by (a) decreasing antibody

and mucous production and (b) allowing the tight

junctions between cells to open as cells swell or

necrose. Both endotoxin and bacteria can move

across the barrier unchallenged. A vicious cycle is

set in motion: with the decrease of cell mass, concomitant loss of mucosal villi decreases the bowel’s

ability to absorb nutrients, which then decreases the

production of immunologically and oncotically active proteins, which then further reduces the ability

of the bowel—as well as the rest of the body—to

function.

Most of the alterations in intestinal function with

stress are not inevitable; they can be prevented by

enteral feeding. Enteral feeding provides the best

means of maintaining the integrity of the intestinal

mucosa. Even so simple a measure as exposing the

mucosa to a continuous normal saline infusion decreases villous atrophy.45 Stimulation of enteroglucagon and gastrin by feeding has a trophic effect

on stomach and intestinal mucosa. Feeding enterally decreases the elaboration of stress hormones
Anesthesia and Perioperative Care of the Combat Casualty

580

TABLE 23-6

ENTERAL FORMULAS AND ORAL SUPPLEMENTS USED AT

WALTER REED ARMY MEDICAL CENTER*

Product Name Citrotein Shakeup Instant Sustacal Ultracal Nutren 1.5

Breakfast (with

8 oz whole milk)

Features Clear liquid High calorie High protein High protein 14 g fiber/L; Calorie-dense

High protein Moderate Vanilla, Vanilla, suitable for to limit volume

Low-fat orange protein chocolate, and chocolate, and most tube-fed Vanilla,

and punch Vanilla, strawberry strawberry patients chocolate,

flavors chocolate, flavors flavors and unflavored

and

strawberry

flavors

Calories/mL 0.66 1.4 1.06 1 1.06 1.5

Protein 41 (25) 50 g 53 (22) 61 (24) 44 (17) 60 (16)

g/L (% Cal)

Carbohydrate 120 (73) 226 g 126 (51) 140 (55) 123 (46) 170 (45)

g/L (% Cal)

Fat g/L 1.6 (2) 33 g 30 (27) 23 (21) 45 (37) 68 (39)

(% Cal)

Fat Source Soy oil Milk fat Milk fat Soy oil 40% MCT; 50% corn oil;

60% soy oil 50% MCT oil

Free Water (%) 93 81 84 85 78

mOsm/kg Water 480 670–715 650 310 410–590

Na mg/L† 710 950–1,200 940 930 750

K mg/L‡ 710 2,150–3,000 2,100 1,620 1,875

P mg/L 1,100 965 930 850 1,050

Ca mg/L 1,100 1,240 1,010 850 1,050

Mg mg/L 420 302 380 340 500

Cal/100% 1,000 1,200 1,080 1,250 1,500

Vit. RDA

Our Cost/L $3.26 1 pkg = $0.36 $2.36 $3.88 $3.88

Source Sandoz Nestle Mead Johnson Mead Johnson Clintec

*All WRAMC enteral products contain vitamin K except Citrotein and Instant Breakfast

†1 mEq Na = 23 mg

‡1 mEq K = 39 mg

MCT: medium-chain triglycerides; LCT: long-chain triglycerides

and the catabolic response to trauma and infection.

Glutamine and alanine both improve nitrogen balance. In studies with animals,27,46 administration of

glutamine alone has been shown to increase mucosal cellularity, improve nitrogen balance, and

improve outcome; however, glutamine is unstable

in solution and is not added to amino acid preparations used in TPN. Glutamine is in some enteral

products, but often not in sufficient amount.46,47

Enteral Formulations

Enteral formulations may be balanced or disease

specific. The latter are, generally speaking, not
Metabolic Derangements and Nutritional Support

581

balanced, with nutrients often in their simplest form:

amino acids rather than intact proteins of high biological value, or dipeptides and tripeptides; an

emphasis on carbohydrate, often as simple sugars,

for calories; and essential fatty acids or mediumchain triglycerides for fats. Often, these ingredients

are not as easily absorbed or utilized as those in

balanced diets. The formulations are for a single,

specific purpose. Renal formulations, for example,

contain no nonessential amino acids, the intent being to promote the reuse of the nitrogen in urea.

Hepatic formulations are often deficient in aromatic amino acids (phenylalanine, tyrosine, and

tryptophan) and contain high concentrations of the

Osmolite HN Isocal Nepro Amin-Aid Peptamen Lipisorb Vivonex T.E.N.

Suitable for Moderate in Renal. High Renal. No Semielemental For fat mal- Elemental

most tube- protein and calorie, high electrolytes Small and absorption Amino acids

fed patients electrolytes protein Essential large peptides Whole protein Very low fat

Unflavored OK for > 3 For oral or amino acids and amino Palatable Usually

years of age tube feeding acids unpalatable

Unflavored Flavor packs

available

1.06 1.06 2 2 1 1 1

44 (17) 34 (13) 70 (14) 19 (4) 40 (16) 35 (14) 38 (15)

141 (53) 133 (50) 216 (43) 366 (75) 141 (51) 117 (46) 206 (82)

37 (30) 44 (37) 96 (43) 46 (21) 39 (33) 48 (40) 3 (2.5)

50% MCT; 80% soy oil; Safflower oil; Soy oil 70% MCT oil; 86% MCT; Safflower oil

50% corn 20% MCT oil Soy oil 30% LCT oil 14% LCT

and soy oils

84 84 71 74 85 83 84

300 270 635 700 270 320 630

930 530 835 < 345 500 734 460

1,561 1,320 1,060 < 117 1,250 1,251 782

758 530 690 0 700 701 500

758 630 1,380 0 800 701 500

304 210 215 0 400 200 200

1,320 2,000 1,900 No vitamins 1,500 2,000 2,000

$5.20 $2.00 $12.33 $18.00 $19.11 $7.96 $15.82

Ross Mead Johnson Ross McGaw Clintec Mead Johnson Sandoz
Anesthesia and Perioperative Care of the Combat Casualty

582

branched-chain amino acids, the opposite of the

condition we normally find in the patient with

hepatic failure.

Balanced formulations, on the other hand, usually contain carbohydrate and fat in a ratio of 70:30,

and provide 1 to 2 kcal/mL. They are generally

isotonic, although formulations with a higher proportion of their calories from carbohydrate have a

higher osmolarity. Carbohydrates are usually provided as oligosaccharides and polysaccharides or

maltodextrins, with fats in the form of mediumchain or long-chain triglycerides. Balanced formulations are often lactose free—as much as possible—

since lactase is often markedly decreased in an

injured or unused gut. The diarrhea (which is not

infrequently seen when enteral feeding is started)

more often is caused by bowel-wall edema from a

low serum albumin, abnormal bowel flora from

long-term antibiotic use, lactase deficiency, or any

combination of the three, rather than a “hypertonic” formulation. Since there is some variation

between formulations, often the substitution of one

balanced formula for another will resolve a problem: feeding a formula higher in carbohydrate, often via the stomach, may help patients with

steatorrhea; a formula with a higher percentage of

calories from fat may help if diarrhea is secondary

to a hyperosmolar (eg, a high-carbohydrate) product. Protein is usually provided at a fixed ratio of

calories to nitrogen, often 150:1. The proteins most

easily absorbed in a balanced formulation are the

intact proteins of high biological value (eg, egg

albumin) and dipeptides and tripeptides. Amino

acids are not easily absorbed.

Electrolytes, vitamins, and trace elements are

added to both balanced and disease-specific formulations; the amounts obviously vary with specific

requirements in the latter. Formulations offer a

wide range of caloric, protein, and electrolyte options (Table 23-6).

Delivery

Before enteral feeding can be initiated, the

patient’s readiness for such feeding must be assessed. Does the patient have a history of gastroesophageal reflux? Prior aspiration? Is the patient

on medication that might promote reflux? The list

is a long one and includes a broad range of drug

types: theophylline, anticholinergics, calcium channel–blocking agents, catecholamines, vasodilators;

in other words, any agent that decreases contraction of the lower esophageal sphincter. Is the patient conscious; if not, does the patient have an

intact gag reflex? Is the gut functional? Does the

stomach empty normally, or does ileus or obstruction interfere? How recently has the patient had

surgery involving the bowel? Unfortunately, bowel

sounds and the passage of flatus are not specific

indicators of gut health. If gastrointestinal output

from all sources (nasogastric tube, ostomies, and

rectum) exceeds 600 mL/24 h, then enteral feeding

is less likely to be successful. Gastroparesis, bowel

obstruction, ileus, pancreatitis, high-output enteric

fistulae, and gastrointestinal bleeding are all relative contraindications to enteral alimentation. The

decision to feed enterally or parenterally (or both)

will be based on not only the presence of one or

more of the above, but also on the extent to which

they are present.

The serum albumin level and the extent of bowel

edema also play major roles in how well enteral

nutrients are absorbed by the bowel. A serum

albumin level of less than 2.7 g/dL will often allow

enough interstitial fluid to remain in the bowel wall

to diminish uptake of enterally provided nutrients,

particularly amino acids and hydrolyzed proteins,

which may require functional enterocytes for absorption. Similarly, an edematous or dysfunctional

colon cannot reabsorb sodium and water properly.

Surgical Access. Two surgical procedures can be

used to gain access to enteral feeding. First, surgical

insertion of a gastrostomy tube may be accomplished either during the initial operative procedure, or may be done percutaneously (via esophagogastroscopy) a few days after surgery. Once the

insertion wound has healed sufficiently—usually

24 hours48—gastric feeding can begin. Second, a

feeding jejunostomy may be placed surgically, either as a separate procedure or through the

gastrostomy tube, and jejunal feeding instituted.

The gastrostomy tube may then be used to decompress the stomach, administer medication, and measure gastric residual volumes if gastroparesis is a

postoperative problem.

Access Via a Feeding Tube. More commonly,

however, nasogastric tubes are used. Nasogastric

tubes are usually made of polyurethane and are

relatively inflexible. They were designed for, and

are commonly used for, gastric decompression, but

are often used for feeding as a matter of convenience. While feeding into the stomach does have a

theoretical advantage in neutralizing gastric pH,

this advantage is offset by the wicklike action of the

nasogastric tube, which prevents competent functioning of the lower esophageal sphincter and allows gastric contents to reflux into the esophagus.

This problem is compounded by gastroparesis or
Metabolic Derangements and Nutritional Support

583

ileus, although use of a nasogastric tube will allow

residual gastric volumes to be followed in these

conditions.

One of the simplest and best-tolerated means of

providing enteral nutrition is by use of a duodenal

feeding tube, inserted either orally or nasally, and

passed into the second portion of the duodenum.

These tubes are made of polyurethane or silicone

rubber and are thin walled and highly flexible.

They come with a wire stylet to stiffen them enough

to insert, and a combination of the stylet, the patient’s

position, gravity, and twisting and turning of the

catheter as it is inserted will get the tube to the

proper position in the duodenum. Duodenal feeding tubes are often designed to be self-passing, with

a weighted tip, and once in the stomach and left to

their own devices, will pass nicely into the duodenum, provided that the tube has not been taped

onto the patient. Always leave some “play” in the

tubing (a loop that will allow the feeding tube to

traverse the pyloric sphincter). It is often helpful to

place the patient with his right side down for several hours. Sometimes, increasing gastrointestinal

peristalsis by using a cholinergic drug like Reglan

(metoclopramide, manufactured by A. H. Robins,

Richmond, Va.), will facilitate placement. However, the medical officer must ensure that the patient does not have a bowel obstruction before Reglan

is administered.

Tube Placement. An easy method of tube placement, which seems to work most of the time, has

been described.49 After the feeding tube is passed to

the stomach with the patient sitting, the head of the

bed is lowered and the patient is placed on his right

side. The feeding tube is then twisted in a corkscrew motion while it is advanced a distance sufficient to pass into the duodenum. Passage through

the pyloric sphincter can often be felt. If resistance

is encountered, the feeding tube, with a loop, should

be taped to the patient. The feeding tube, now free

to advance on its own, passes more often than not.

Initial tube placement may be checked by auscultation; however, the position of the tube is always

verified by X-ray examination before feedings are

instituted.

Tolerance to Feeding

Tolerance to feeding should be assessed by beginning the infusion at a low rate (eg, 30 mL/h) for

the first 24 hours. The patient should be closely

monitored for abdominal distention or cramping,

and for the onset of nausea, vomiting, or diarrhea.

Residual volumes may be assessed if a nasogastric

tube is used for feeding, or if a nasogastric tube was

left in place when the feeding tube was placed. The

relative position of both tubes is important in assessing residual volume. If the feeding tube has

slipped back to the duodenal bulb or stomach, or if

the nasogastric tube is at the pylorus, then large

residual volumes may not accurately reflect the

function of the stomach and the bowel.

Monitoring

In general, enteral nutrition requires at least

as careful monitoring as parenteral. Tubing must

be changed daily, and formula at least every

8 hours, to prevent bacterial overgrowth. Intake

and output must be followed as closely as they are

in parenteral nutrition. Residual volumes should

be checked every 4 hours, initially. The risk of

aspiration is significant in enteral feeding; even the

presence of two sphincters (pyloric and lower esophageal) between the feeding-tube outlet and the lungs

does not completely remove the risk. The head of

the bed should be elevated 30° during enteral alimentation, with feeding interrupted, if necessary,

to allow for sleeping.

Diarrhea

Diarrhea (passage of more than 300 g or 300 mL

of liquid or semisoft stool per day) can develop in

up to three fourths of critically ill patients who

receive enteral alimentation. As stated before, this

is usually due to atrophy of villi, bowel-wall edema,

and the use of multiple antibiotics, with consequent

disruption of the normal intestinal flora. Pseudomembranous colitis due to Clostridium difficile must

always be considered. Therapeutic response to

diarrhea includes replacement of lost fluid and electrolytes, decreasing the rate of feeding, changing to

a different product, and adding Kaopectate (manufactured by Upjohn, Kalamazoo, Mich.; the active

ingredients are kaolin and pectin) to the formula.

Fifteen to 30 mL of Kaopectate administered every

2 to 6 hours will often slow diarrhea. Kaopectate

binds bacterial toxins and is often useful in diarrhea

due to bacterial overgrowth. It also apparently

stimulates villous trophism (soluble fiber polysaccharides have a similar effect on mucosal growth

and function, and have been shown50 to improve

recovery from inflammation). Remember to flush

the feeding tube afterwards; frequent flushing ensures the tube’s continued patency and reduces the

need for replacement. Opiates should be avoided,

as they may worsen or induce ileus and allow fur-
Anesthesia and Perioperative Care of the Combat Casualty

584

ther bacterial overgrowth. Water may be added if

the patient has a free-water deficit (eg, large insensible losses, hypernatremia due to diuresis), but

enteral formulae for diarrhea rarely require dilution, as most are isotonic. Decreasing the osmolarity to 150 mOsm may be tried, but if a decrease in

rate and osmolarity and the addition of Kaopectate

do not solve the problem, then fat and carbohydrate

malabsorption should be assessed with stool fat, Dxylose, and finally breath hydrogen laboratory tests,

looking for bacterial overgrowth. Stool specimens

should be sent to the laboratory early to be tested

for Clostridium difficile toxin; if the test is negative

but diarrhea persists, then consider evaluation with

a flexible sigmoidoscope.

Maintaining the Feeding Tube

Clogging of feeding tubes can be minimized by

flushing the tube with water after use (eg, after

administering medication, when feeding bags are

changed). Medications in pill form should never be

crushed and given through a feeding tube. Pills and

tablets should be dissolved in 15 to 30 mL of water,

injected into the tube by Toomey syringe, and

flushed. Should a clog develop, a small amount of

a carbonated cola soft drink injected into the feeding tube may dissolve it.

Feeding tubes tend to migrate and should be

adequately secured. They should be taped (always

with a loop) to the patient’s forehead or cheek; take

care not to put pressure on the nares. The tubes may

also be more firmly hobbled should their wandering become a problem.

Assessment of Nutritional Repletion

The assessment and consequences of nutritional

depletion are well described: a loss of 40% of total

body weight is usually fatal; there are generally

accepted “panic values” for electrolytes and micronutrients; and the value of nutritional support is

widely accepted. Assessment of nutritional repletion is not so clear cut. The question of how to

monitor nutritional repletion has been asked by a

number of authorities: there is a difference between

monitoring structural repletion versus monitoring

cell function. Nutritional repletion alters the performance of cells before it restores mass, by altering

membrane ion transport and by returning enzyme

function to normal. Nuclear magnetic resonance

studies using phosphorous 31 labeling have shown

a fall in oxidative phosphorylation in malnutrition,

implying a decrement in mitochondrial function.

Cell energetics return to a more normal function

before protein synthesis restores cell mass but still

require 2 to 4 weeks of nutritional repletion in a

severely malnourished patient. Three fourths of the

energy liberated by the hydrolysis of ATP is used to

maintain ion gradients across cell membranes, even

at the expense of protein synthesis, in a malnourished patient. Protein synthesis is a metabolically

expensive cell function, requiring five molecules of

ATP for each amino acid incorporated into a protein. It should come as no surprise that cells take

care of their basic requirements first.51

As an index of nutritional repletion, serum albumin has a sensitivity of only about 10%. While the

half-life of albumin in normal individuals is 18

days, it is much shorter in catabolic patients. Albumin levels fall before significant malnutrition occurs in patients who are starved, stressed, or both,

because of ongoing catabolism of nonessential proteins. In the stressed patient, protein production is

shifted to acute-phase proteins. Large-scale volume expansion, not uncommon in critically ill patients, also lowers albumin levels significantly.

Generally, a level of 2.5 to 3.0 g/dL reflects a mildto-moderate depletion of the albumin pool, 2.0 to

2.5 g/dL a moderate depletion, and less than 2.0 g/dL

a severe depletion, but this assessment may not

accurately reflect the patient’s overall nutritional

status. Albumin rises slowly following nutritional

repletion, usually taking weeks to rise in patients

receiving TPN. Any earlier rise may be artifactual

and due to contraction of the extracellular water

pool, rather than to an actual increase in albumin

mass. Albumin may actually rise more rapidly with

enteral feeding than with TPN, although bowelwall edema may preclude this route until adequate

oncotic pressure is established and tissue edema

reduced. Because albumin is necessary to maintain

intravascular oncotic pressure, supplementation

may be accomplished by continuous infusion at 4, 8,

or 12 mL/h to increase serum osmolarity and decrease bowel-wall edema in preparation for enteral

feeding. Bolus supplementation of serum albumin

is not effective in mobilizing fluid.

Transferrin is also a nonsensitive indicator of

nutritional repletion, even though the half-life of

transferrin (8 d) is shorter than that of albumin, and

therefore turnover is faster. Transferrin is a necessary component of the white blood cell response to

infection and inflammation. Levels tend to increase

earlier than serum albumin levels with feeding,

partly as a reflection of this function. Transferrin

levels also increase with iron deficiency, as the

protein is no longer bound. Levels between 100 and
Metabolic Derangements and Nutritional Support

585

150 mg/dL reflect a moderate depletion of the pool;

less than 100 mg/dL, a severe depletion.

Thyroxine-binding prealbumin is more sensitive

than either albumin or transferrin to nutritional

repletion. It has a half-life of 1.9 days and is a fairly

useful indicator of catabolism and protein synthesis. The fall in this protein in critical illness may be

related to changes in thyroxine levels rather than to

malnutrition, however, making clinical application

difficult. Normal levels in men are between 19 and

39 mg/dL; in women, 19 and 30 mg/dL.

Similarly, retinol-binding protein is a more sensitive indicator of nutritional repletion than is either albumin or transferrin, but the use of this

plasma protein as an indicator has limited utility

outside academic medical centers.

Fibronectin levels provide a very sensitive barometer of nutritional depletion and repletion.

Fibronectin is rapidly consumed during critical illness, with a corresponding fall in serum levels.

Levels peak early with adequate repletion, but after

1 to 2 weeks become relatively useless in assessing

nitrogen balance. Most other indices have problems as well.

The Creatinine-Height Index3 overestimates

muscle mass in critical illness, and is sensitive to

renal dysfunction. Cutaneous reactivity and lymphocyte counts are nonsensitive and nonspecific

indices of nutrition, as immune function is affected

by multiple factors: infection, uremia, cirrhosis,

hepatitis, steroids, burns, hemorrhage, trauma, general anesthesia, and others.

The urinary urea nitrogen test is extremely useful in assessing the catabolic rate, and therefore the

physician’s ability to balance protein breakdown

with nutrition repletion. While it is a gross measure, the nitrogen balance is still the best indicator

of the adequacy of repletion of protein. Adequacy

of caloric repletion is best assessed by indirect calorimetry.

The problem of providing nutritional support to

casualties in the theater of operations has recently

been addressed.52 At present, the limitations of

deployed resources may not allow either enteral or

parenteral forms of nutritional support; however,

both forms should be available in fourth-echelon

hospitals. Although parenteral nutrition is probably not possible in the third echelon during a major

war, enteral nutrition—being much more feasible

logistically—is certainly an acceptable alternative.

For this reason, surgeons should be encouraged to

insert feeding tubes during resuscitative surgery on

all casualties who are likely to require nutritional

support.

SUMMARY

a variety of essential, life-sustaining processes.

Metabolic intermediates in excess of the body’s

immediate energy needs are converted into fatty

acids for storage in fat cells, or into glucose, which

is stored as glycogen in liver and muscle. Although

at any given moment the metabolism of glucose is

the major source of the body’s energy-supplying

intermediates, lipids are the major form of nutrient storage. Proteins can serve as storage deposits

for amino acids; their primary role, however, is

structural, and protein metabolism results in functional impairment. Interconversion of glucose, fatty

acids, and amino acids is not perfect; although glucose can be converted into fat and certain amino

acids can be converted into glucose, fatty acids are

not easily converted into glucose. During uncomplicated starvation, when glucose is in short supply, free fatty acids (or ketone bodies formed from

their partial metabolism) are used by most organs

in place of glucose. Low circulating insulin levels

are necessary for the metabolic adaptation to starvation.

When stress and physical exertion are superimposed on starvation, not only are overall metabolic

Metabolic interventions are important in the treatment of wounded casualties because the common

perception of the soldier as a vigorous, muscular

mesomorph obscures reality: combat casualties are

frequently nutritionally depleted or even frankly

malnourished. Unfortunately, however, the applicability of nutritional therapy for combat casualties

is a function of the nature of the deployment. In

short but intense conventional wars and in operations other than war, only limited medical assets

will be deployed in the combat zone, and they will

be used primarily for resuscitative surgery. Casualties who require nutritional support will probably

be evacuated for the needed treatment to hospitals

at the fourth echelon or in the continental United

States. Ideally, however, nutritional support would

begin prior to evacuation.

The primary constituents of ingested food—

carbohydrates (hexoses, of which glucose is preeminent), fats (triglycerides), and proteins (amino

acids)—are interconverted by the TCA cycle found

within mitochondria. Metabolic intermediates are

formed within the mitochondria, which store

chemical energy in molecular bonds to be used in
Anesthesia and Perioperative Care of the Combat Casualty

586

demands increased, but mobilization of fatty acids

is also impeded by elevated levels of stress hormones such as catecholamines, cortisol, and glucagon. Hence, when physical stress occurs with starvation, there is an increased need for glucose, which

(because of the lack of metabolic machinery allowing free conversion of fatty acids to glucose) can

only be obtained through the process of gluconeogenesis: amino acids derived from the catabolism of

body proteins are converted into glucose. The need

for glucose and the associated accelerated catabolism of protein are even greater when a wound is

present, because healing tissue is an obligate consumer of glucose. Protein catabolism is further

accelerated when the wound is septic, owing to the

formation of mediators of inflammation such as IL1 and the eicosanoids. Thus, the combat casualty

with severe wounds that have become septic is both

hypermetabolic (ie, the REE is 30%–60% greater

than normal) and hypercatabolic with a negative

nitrogen balance (ie, more than 10 g of urea nitrogen

is excreted via the urine per day). Paradoxically,

both hyperglycemia and hyperinsulinemia are frequently present, indicating that the hormonal milieu associated with injury and sepsis has induced a

state of resistance to the normal biological effects of

insulin.

Ideally, optimal metabolic management of the

hypermetabolic and hypercatabolic combat casualty requires knowledge of both the REE and the

nitrogen balance. Caloric intake can then be set at

30% to 40% of measured energy expenditure, and

the amount of nitrogen at 1g/150 kcal of caloric

intake. Since the equipment for indirect calorimetry is not likely to be available in deployable hospitals, a more empirical approach will be necessary

there (eg, giving 40 kcal/kg/d, with nitrogen being

given in the ratio of 1 g/200 kcal. At least half the

total caloric intake should be in the form of carbohydrates. The route of administration will depend on

whether the gastrointestinal tract is functional. If it

is, the enteral route is preferable since it is safer,

cheaper, and, perhaps most importantly, it helps to

preserve the integrity of the intestinal mucosa.

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EXCERPT FROM WALTER REED ARMY MEDICAL CENTER

INFECTION CONTROL POLICY AND PROCEDURE GUIDE

For the benefit of the interested reader, the following excerpt is reprinted from Roup BJ, ed. Lieutenant

Colonel, Army Nurse; Chief, Infection Control Service, Department Of Nursing. Walter Reed Army Medical

Center Infection Control Policy and Procedure Guide. 3rd ed. Washington, DC: Walter Reed Army Medical

Center; November 1991; previous editions February 1987, June 1989.

PERIPHERAL AND INTERMITTENT INTRAVENOUS THERAPY

I. GENERAL

This SOP establishes WRAMC policy for the insertion and maintenance of peripheral intravascular devices,

fluids, delivery systems, and the procedure to be followed in the event of suspected infection.

II. SPECIFIC

A. IV Insertion

1. Equipment

a. IV solution

b. IV tubing set, primary

c. Steel needle or plastic catheter

(NOTE: Steel needles, eg, butterfly or scalp vein, are recommended over plastic catheters as they appear to cause

less phlebitis. Plastic catheters should be used when a secure route for vascular access is imperative or when

administered drugs may tissue damage if they infiltrate.)

d. Iodophor or alcohol for skin prep

e. Tourniquet

f. Tape

g. IV stand

h. Waste container

i. Sterile dressing (2 x 2 gauze pad or semi-permeable plastic membrane)

j. Chux (blue pad)

k. Gloves

2. Procedure

a. Wash hands with antiseptic soap and water for at least 30 seconds.

b. Visually inspect IV container for cloudiness or particulate matter. Check glass bottles for cracks; squeeze

plastic bags for air leaks. DO NOT USE IF STERILITY IS SUSPECT.

c. Connect tubing to solution container using aseptic technique. Glass bottles require vented tubing;

plastic bags require non-vented tubing.

(NOTE: Use of extension tubing, especially 3-way stopcocks is discouraged. Frequent manipulation and open

stopcocks provide microorganisms direct access to the blood stream. If 3-way stopcocks are used, the cap covering the

unused port should be a Luer-Lok cap or taped in place.)

d. Fill entire length of tubing with solution and close tubing clamp.

e. Select venipuncture site in an upper extremity.

(NOTE: The risk of infection with lower extremity cannulation is extremely high. Cannulae inserted into lower

extremities should be removed as soon as venous access in an upper extremity is established.)

f. DO NOT SHAVE insertion site. Remove excess hair by clipping with scissors.

g. Place Chux under extremity to protect bed linen.

h. Apply tourniquet and palpate blood vessel. (A tourniquet that is too tight will not allow the vein to

distend.)

i. Cleanse site with prep solution, using friction from center to periphery in a 2" diameter spiral.

1) PREFERRED PREP: Cleanse site with iodophor, eg, Betadine. Allow to dry. DO NOT remove with

alcohol. The antimicrobial action depends in part on the continued release of free iodine.

2) ALTERNATE PREP: Cleanse site with isopropyl alcohol for AT LEAST ONE MINUTE and allow to

air dry. (Alcohol contact time is the kill factor.)
Anesthesia and Perioperative Care of the Combat Casualty

590

j. After the venipuncture site has been prepped, DO NOT touch the skin with your finger unless wearing

a sterile glove.

k. Put on gloves.

l. Holding the skin taut, insert the needle/catheter along-side the vein, bevel up, about 1⁄2 inch from the

site of vein puncture. Carefully puncture the vein and thread the needle into it. Observe for blood

return. If blood return is present, continue with procedure.

(NOTE: If no blood return is obtained, manipulate the needle carefully to gain entry into vein. If unsuccessful,

withdraw the needle, obtain fresh needle, prep skin again, and make another attempt. DO NOT MAKE REPEATED

ATTEMPTS USING THE SAME NEEDLE.

m. If using plastic catheter, withdraw the needle.

(NOTE: Once the catheter has been withdrawn, do not reinsert it into the catheter as it may sever the catheter and

cause it to “float” through the circulatory system.)

n. Connect filled tubing to needle/catheter hub, release tourniquet, open tubing clamp and adjust flow to

appropriate rate of infusion.

o. Secure needle/catheter with small piece of tape (chevron style). DO NOT place tape directly over

venipuncture site.

p. Apply sterile dressing. Two methods are acceptable:

1) Apply dry, sterile 2 x 2 gauze pad. Secure with tape. Avoid bulky dressing.

2) Apply semi-permeable transparent dressing following manufacturer’s guidelines.

q. Anchor tubing securely to patient’s extremity.

r. Record date, time of insertion, type of device and initials of person performing venipuncture on a piece

of tape. Attach to IV dressing. Record same information in the clinical record.

s. Label IV tubing with appropriate dated label (per Department of Nursing/Department of Nursing

Administrative Policy guidelines) and record date, time and initials on the label.

t. Instruct patient to report signs and symptoms of phlebitis, infection or infiltration (pain, burning,

redness, swelling, numbness or fluid/blood seepage).

u. Remove all excess/used supplies and equipment from the patient’s room. Dispose of needles and

syringes into plastic sharps container; trash into the waste basket.

B. IV Maintenance

1. Inspect IV insertion sites for evidence of phlebitis, pain, infiltration, leakage or blockage at least daily and

every time a new IV solution container is hung. If the patient has unexplained fever, pain, or tenderness

at the site, the gauze dressing should be removed and the site visually inspected.

2. Change the IV tubing and dressing at the same time the IV site is rotated: EVERY 72 HOURS. Start the IV

at another site BEFORE the old set is removed.

(NOTE: This procedure should be accomplished as one maneuver to reduce the amount of manipulation of the

system.)

3. When the patient’s physician has determined that sites cannot be changed every 72 hours:

a. Meticulous site care should be performed every 72 hours; more often if indicated.

b. Document in the clinical records the reason(s) for not rotating the sites, and observations of the site.

4. 250 ml container should be used for “TKO” or “KVO” infusions.

5. Fluid containers must be clearly labeled with patient’s name, added medications, and time-stripped for

easy monitoring of fluid volume infused.

6. Fluid container must be changed at least every 24 hours.

C. Site Care

1. Remove dressing down to, but not including, chevron tape.

2. Remove old iodophor with alcohol.

3. Cleanse site thoroughly with iodophor solution.

(NOTE: Alcohol may be used for iodophor-sensitive individuals.)

4. Allow to dry. DO NOT remove with alcohol.

5. Redress with sterile dressing.

(NOTE: Site care is to be performed when cannulae are left in longer than 72 hours or when dressing becomes wet or soiled.)
Metabolic Derangements and Nutritional Support

591

6. Record date of dressing change, date of insertion, type of device, and initials on piece of tape; attach to

dressing. Record dressing change in the clinical record with observations of site appearance.

D. Administration of IV Piggyback Medications

1. All piggyback medications should be mixed in the pharmacy.

2. Connect the secondary (piggyback) tubing to the medication container using aseptic technique.

3. Attach secondary tubing to the primary tubing with a needleless connector. Ascertain that connection is

secure.

4. Lower the primary infusion container to a level lower than the piggyback container, using the hook

provided with the tubing.

5. Set flow rate for proper infusion period.

(NOTE: Infusion periods are listed on the label of all IV piggybacks prepared in the pharmacy.)

6. After infusion of the medication, clamp the secondary tubing, raise the primary container to its original

height and leave the secondary tubing connected to the primary tubing.

(NOTE: Secondary tubing can be flushed by lowering the piggyback below the level of the primary bag, flush and

drain back into primary tubing.)

7. When ready to administer the next dose, remove the empty bag and replace it with the new one. Fill

secondary tubing by lowering the secondary container and opening the clamp on the secondary tubing.

Close the clamp and proceed as in 4. and 5. above.

8. When administering more than one medication, and the medications are compatible, follow the procedure

outlined in 7. above.

9. When administering incompatible medications, lower the secondary set WITH THE EMPTY MEDICATION CONTAINER ATTACHED and open the clamp on the secondary set. Fluid will flow through the

tubing into the previously empty medication container and proceed with steps 4–6 above.

(NOTE: Piggyback tubing is changed every 72 hours, the same as primary tubing.)

E. Administration of Intermittent Infusions

1. Ascertain that the “Heparin Lock” has the appropriate needleless connector component attached.

2. Using a needleless connector component attached to a syringe containing sterile normal saline for injection,

connect the syringe to the Heparin Lock and aspirate slightly. If blood return is noted, inject 2–3 cc of

normal saline solution to assure patency of the device and to clear device of residual heparin.

3. Attach infusion to heparin lock using a needless connector component.

4. Infuse medication as ordered.

5. At completion of the infusion, unhook the tubing from the heparin lock.

6. Using a needleless connector component attached to a syringe containing heparin solution, connect the

syringe to the heparin lock and flush the lock.

7. Discard tubing. A new set of IV tubing will be used for each infusion.

F. IV Infusion Pumps

1. One piece administration sets are recommended. Follow the manufacturer’s guidelines for set-up and line

flushing procedure.

2. IMPORTANT: Check under site dressing for swelling frequently. Use of a pump increases the risk of

extensive infiltration if a needle or catheter becomes dislodged.

3. All surfaces of the pump must be thoroughly cleaned when soiled, and between patients, using a

housekeeping disinfectant detergent or product recommended by the manufacturer.

G. If IV-Associated Sepsis Is Suspected

1. Culture any purulent drainage around catheter site prior to cleansing the skin.

2. Cleanse skin around catheter with antiseptic to remove skin organisms.

3. Clip off catheter tip with sterile scissors, dropping catheter into DRY, STERILE specimen cup. Request

quantitative cultures of the tip. Send to laboratory IMMEDIATELY to prevent drying and death of

organisms.

(NOTE: In addition to routine identification data, culture request should include type of specimen (catheter tip), site

of catheter (R forearm), signs and symptoms.)
Anesthesia and Perioperative Care of the Combat Casualty

592

4. A blood culture should be drawn from the opposite arm after carefully prepping the venipuncture site with

iodophor.

5. If IV solution contamination is suspected:

a. Cap end of IV tubing with a capped, sterile needle.

b. Send ENTIRE IV set-up and solution container to the laboratory for culture. DO NOT disconnect any

part of the set-up.

c. Call Infection Control IMMEDIATELY (phone 782-4350/4351) to alert them of the problem.

(NOTE: The laboratory will NOT culture IV systems without coordination with Infection Control.)

6. Record observations and actions in the clinical record.

7. Complete WRAMC Form 1811, Quality Control and Risk Management Report, and submit through proper

channels.

RECOMMENDATIONS FOR CENTRAL INTRAVASCULAR LINE INSERTION

I. GENERAL

A. Purpose: To provide guidelines to all personnel involved in performing or assisting with the insertion of a

central intravascular catheter.

B. References:

1. Miller, S., Sampson, L.K., Soukup, S.M. AACN Procedure Manual for Critical Care, Philadelphia: W.B.

Saunders Co., 1985, pp. 47–53.

2. Hospital Infections Program, Center for Infectious Diseases, CDC, Atlanta, Ga., 1985.

3. Nutrition Support Core Curriculum 2nd ed., C. Kennedy Caldwell, P. Guenter, eds., American Society for

Parenteral and Enteral Nutrition, 1988.

II. SPECIFIC

A. Equipment

*Caps

*Masks

*Sterile gown(s) for physician(s)

 **Sterile gloves (appropriate size)

*Sterile drapes

*Acetone (10%)/alcohol (70%) swabsticks (2 packs of 3)

*Povidone/iodine scrub swabsticks (2 packs of 3)

*Alcohol (70%) swabsticks (2 packs of 3)

*Povidone/iodine solution swabsticks (2 packs of 3)

*1% Lidocaine

*4 x 4s

*2 x 2s

*4-0 silk suture on cutting needle

*22g needle (1)

*10 cc syringes (2)

*20g needle (1)

*25g needle (1)

*Scissors

*Hemostats

Heparin Solution (100 units per cc)

Catheter kit for insertion

Tape

Alcohol wipes

*All items contained in Central Venous Insertion Tray

 **Size 71⁄2 gloves in Central Venous Insertion Tray

Also need Central Venous Dressing Tray which contains:

2 prs sterile gloves (size 71⁄2)

Acetone (10%)/alcohol (70%) swabsticks (pack of 3)
Metabolic Derangements and Nutritional Support

593

Povidone/iodine scrub swabsticks (pack of 3)

Alcohol (70%) swabsticks (pack of 3)

Povidone/iodine solution swabsticks (pack of 3)

Skin prep swabstick

2 x 2 gauze

Sterile cotton tip applicator

Scissors

Masks (2)

Cap

Elastoplast dressing

B. Procedure

1. Explain procedure to patient to promote understanding and minimize anxiety. Obtain written consent

(Physician).

2. Organize and assemble supplies and equipment at bedside.

3. Wash hands; turn off faucet with paper towel.

4. Place patient in supine and Trendelenburg position of at least 15 degrees. Place a rolled towel between

scapulae with head turned away from insertion site. This positioning promotes maximum filling and

distention of the subclavian vein to the angle between the clavicle and the first rib. The increased pressure

created in the upper thorax also decreases the possibility of air embolism.

5. Place a mask over patient’s mouth and nose (and trach). If patient is unable to tolerate a mask, use a towel

or drape as a barrier between patient’s mouth/nose/trach and insertion site.

6. Don gown, cap, and mask to avoid contamination of site and equipment. Open and prepare insertion tray.

7. Don sterile gloves and begin preparation of skin for insertion. The area to be prepped should extend from

above the clavicle to the nipple line and from the shoulder to just beyond the sternal notch. Cleanse with

friction using a circular motion from center to periphery. The following order should be observed.

a. Start with the acetone/alcohol swabsticks to remove skin fats and oils which may harbor pathogens. It

is also effective in removing old tape and glue from previous dressings.

b. Cleanse area with povidone/iodine SCRUB swabsticks using same friction and circular motion from

center to periphery.

c. Remove povidone/iodine with alcohol swabsticks. The povidone/iodine scrub solution is now contami

nated with organisms. If left on skin, it will cause irritation because it contains soap. Again, use a

circular motion from center to periphery.

d. Paint area just prepped with povidone/iodine solution swabsticks. This provides a protective barrier

against skin organisms.

8. Apply sterile drapes so that only area not covered is the prepped area.

9. Assist physician in donning mask, cap, sterile gown and sterile gloves.

10. Open catheter kit and drop in sterile tray or allow physician to remove contents.

11. Clean top of heparin flush solution with alcohol wipe and hold for physician to draw up sufficient solution

to flush catheter prior to insertion.

12. Physician will insert catheter. Monitor patient during catheter insertion. Assist patient to remain immobile.

Notify physician if breaks in aseptic technique are noted. Assist physician as necessary.

13. Catheter should be secured to skin by 4 separate sutures by the physician. This is necessary to minimize

movement of the catheter and prevent accidental dislodgement. Line should be sutured in the vertical

position. Avoid suturing line horizontally toward the shoulder because of extra stress on the sutures as the

patient ambulates.

14. The area around the insertion site and sutures should be reprepped and an occlusive dressing applied

using the following steps:

a. Open Central Venous Dressing Tray.

b. Don sterile gloves (and cap and mask if not already wearing them).

c. Using acetone/alcohol swabsticks remove all blood from around the insertion site and sutures. Blood

left on the skin may provide medium for bacterial growth.

d. Reprep the skin by using povidone/iodine scrub swabsticks. Use a circular motion and start at the

insertion site, then around the sutures.

e. Remove povidone/iodine scrub with the alcohol swabsticks starting at the insertion site using a circular

motion.

f. Paint the area with povidone/iodine solution and blot dry with 2 x 2s. Use the cotton tip applicator to

remove any extra solution from under the line.

g. Place folded 2 x 2 over the insertion site and line down to and including the sutures. This is to prevent

the occlusive dressing from sticking to the line and sutures.
Anesthesia and Perioperative Care of the Combat Casualty

594

h. Cut the Elastoplast to fit over the insertion site and sutures. Round all corners and be sure 2 x 2s are

completely covered.

15. Remove mask from self and patient. Also remove rolled towel from patient’s scapula. Apply skin prep

around edge of Elastoplast and tape around the edges of the dressing.

16. Label the dressing with date, time and initials of person doing the dressing.

17. Remove all supplies and wash hands.

18. Ensure that a STAT portable chest X-ray is obtained before ANY infusion is started. The patient is to

remain in bed until confirmation of line placement is obtained.

19. Chart the procedure, any problems encountered, patient’s tolerance of the procedure, and verification of

line placement.

20. Infusions may begin only after verification of line placement. If patient has a triple lumen catheter and

is to receive TPN, do not infuse anything through the DISTAL port except TPN. The other two ports may

be used to draw blood or infuse other solutions.

III. RELATED CARE

A. Assess and monitor the patient and IV site q2h for complications:

1. Pneumothorax

2. Hemothorax due to subclavian or innominate artery puncture

3. Hematoma at the puncture site

4. Myocardial perforation related to the catheter advancement

5. Infection

6. Phlebitis

7. Thrombosis

8. Air embolism

9. Mediastinal fluid infusion (hydrothorax)

10. Catheter shearing or embolism

11. Brachial plexus injury during subclavian catheter placement

12. Osteomyelitis related to subclavian insertion.

B. Maintain catheter asepsis:

1. Change central line dressing every 48–72 hours, or whenever the catheter is changed. If a fever occurs,

obtain culture of site and blood cultures.

2. If dressing becomes soiled, disrupted, or non-occlusive, it must be changed.

C. The patient is to remain supine until line placement is confirmed. Reposition the patient following catheter

insertion; elevate the head of the bed. Place the patient in the recumbent position when the IV tubing is

disconnected from the catheter to minimize the risk of air embolus.

D. Monitor the IV flow rate at frequent intervals; all TPN and IV solutions with medications must be infused via

an infusion pump (IMED).

E. Removal of catheter:

1. The recommended duration of a central line is 72 to 96 hours; however, under certain circumstances, a

patient’s clinical condition may necessitate a central line remaining in a site for a longer period. This is

acceptable if proper documentation by the physician is in the Doctor’s Progress Note (SF 509) regarding

the circumstances, clinical need and the condition of the central line site, and is accomplished on a daily

basis.

2. At the earliest sign of sepsis, the central line site should be changed in conjunction with other therapeutic

measures.

3. Procedure for removal of catheter when appropriate:

a. Apply non-sterile gloves. Remove dressing.

b. Remove the sutures, using a suture removal kit.

c. Have the patient take a deep breath and hold. Withdraw the catheter out and upward away from the

skin.

d. Inspect the catheter to make sure it is intact.

e. Using a second sterile suture removal kit, culture the catheter tip if infection is suspected.

f. Apply pressure to the area to prevent bleeding.

g. Apply a sterile occlusive dressing.

h. Assess the patient and monitor for complications after catheter removal.
Metabolic Derangements and Nutritional Support

595

RECOMMENDATIONS FOR CENTRAL VENOUS CATHETER DRESSING CHANGES

I. GENERAL

A. This procedure guideline applies to all personnel involved in performing or assisting with central venous

catheter dressing changes and is the procedure used by the Nutrition Support Service, WRAMC.

B. Frequent use of central lines for monitoring and IV administration of fluids, medications, and/or total

parenteral nutrition (TPN) requires a standard and meticulous method of care to minimize the risk of

contamination and sepsis. In support of the current literature and national standards, central line dressings

will be changed every 24 to 72 hours (depending upon local protocols), whenever the catheter is changed,

or when there is drainage and/or sign of infection at the site.

II. SPECIFIC

A. Equipment

1 cap

2 masks

1 clean gown

1 roll of tape

Central Line Dressing Kit Containing:

2 pairs of gloves

1 triple pack acetone-alcohol swabsticks

1 triple pack povidone-iodine scrub swabsticks

1 triple pack isopropyl alcohol swabsticks

1 triple pack povidone-iodine solution swabsticks

l protective dressing swabstick (skin prep)

1 4 x 5 Elastoplast dressing

2 2 x 2 cotton gauze sponges

1 cotton tip applicator

1 pair scissors

B. Procedure

l. Wash hands. Explain the procedure to the patient and/or significant others. Check for povidone-iodine or

tape allergy.

2. Organize supplies and equipment at the bedside to decrease the amount of time that the site is open to the

air.

3. Don gown, mask and cap. Place the patient in a supine with head turned away from catheter insertion site

to decrease potential for contamination by nursing personnel and by patient secretions. Place a mask over

patient’s mouth and nose (and trach) if patient is able to tolerate. If patient is unable to tolerate the mask,

use a towel as a barrier between patient’s mouth/nose and insertion site.

4. Open central line dressing kit and don a pair of gloves.

5. Remove present dressing carefully to minimize trauma and prevent accidental dislodgement of catheter.

Place soiled dressing in proper trash receptacle.

6. Inspect the skin and catheter site infection, leakage, or other mechanical problems.

7. Don sterile gloves.

8. Cleanse the insertion site with acetone/alcohol swabsticks, working in a circular motion from the insertion

site outward to the edge of the dressing border. This removes adhesive material and defats the skin. Repeat

3 times. Do not apply over broken skin.

9. Working in a circular motion from site outward, cleanse the insertion site and distal portion of the catheter

with the povidone-iodine scrub swabsticks 3 times to remove bacteria and fungi from the skin and catheter.

10. Working in a circular motion as before, cleanse the site of the povidone-iodine scrub with alcohol

swabsticks 3 times to remove the povidone-iodine scrub.

11. Paint a 3 x 6 area from site to periphery with povidone iodine solution swabsticks 3 times. Blot excess or

pooled solution. Allow to dry. This provides a protective barrier against pathogens.

12. Place a folded 2 x 2 over the insertion site and line down to and including the sutures. This is to prevent

the occlusive dressing from sticking to the line and sutures.

13. Cut the Elastoplast to fit over the insertion site and sutures. Round all corners and be sure 2 x 2s are

completely covered.
Anesthesia and Perioperative Care of the Combat Casualty

596

14. Apply Elastoplast. Paint around edges of Elastoplast with skin prep and tape all around dressing.

15. Tape all connections or ensure that all Luer lock connections are tight. This prevents dislodgement of the

tubing from the catheter and reduces the potential for air embolism. Tape edges of dressing, if necessary.

16. Write the date and time of dressing change, and your initials on the dressing. This allows for easy

identification and documentation of the interval to change the line and the dressing.

17. Document the dressing change and the condition of the insertion site, the patient’s tolerance of the

procedure, and any problems encountered in the nursing notes.

C. Related Care

1. Inspect site frequently for signs of infection, inflammation, drainage, and infiltration.

2. Whenever the catheter is changed, the dressing must be changed.

3. IV tubing for TPN must be changed every 24 hours —or every bag change. Dressing should be changed

every Monday, Wednesday, Friday or according to local protocol (ie, ICU).

SUMMARY TABLE FOR SITE, DRESSING, AND TUBING CHANGES

I. GENERAL

A. Change all IV fluid containers every 24 hours.

B. Handle all intravascular devices with aseptic technique.

 II. SPECIFIC

Duration of Dressing Tubing Documentation of

Site/Needle Change Change Appearance of Site

Central (Short Term)

According to Protocol 48–72 h 24*–72 h With dressing change

Central (Long Term)

N/A 48–72 h 24*–72 h 24 h

Implanted Devices

6–7 d 48–72 h 24*–72 h 24 h

Peripheral, Arterial

72–96 h 48–72 h 48–72 h 24 h

Peripheral, Intravenous

72 h 72 h 72 h 24 h

Piggyback Meds,

Continual Infusion

72 h N/A 72 h N/A

Piggyback Meds,

“Heparin Lock”

72 h N/A Each infusion N/A

*With every new bag of TPN or every 72 h for all other fluids
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

597

DANIEL P. STOLTZFUS, M.D.*; AND JAMES A. GEILING, M.D.†

Chapter 24

INTRODUCTION

EPIDEMIOLOGY

The Civilian Experience

The Military Experience

Traumatic Injury

Trauma-Related Sepsis and Septic Shock

Cellular and Subcellular Mechanisms Leading to SIRS/MODS

Components and Products From Microorganisms Giving Rise to SIRS/MODS

Cellular Components Contributing to SIRS/MODS

Endogenous Mediators

ORGAN-SPECIFIC RESPONSES

Cardiovascular Response

Pulmonary Response

Renal Dysfunction

Neurological Manifestations

Metabolic and Endocrinological Responses

Immunological Aberrations

Surgery in the Immunocompromised Patient With Sepsis/SIRS

Hematological and Coagulation Defects

Dermatological and Ophthalmological Manifestations

DIAGNOSIS AND MONITORING

Hematological Evaluation

Microbiologic Evaluation

Sophisticated Bedside Monitors

Radiological Procedures

Surgical Reexploration

THERAPEUTIC MODALITIES

Fluid Resuscitation

Selection of Resuscitation Fluid

Tissue Oxygen Delivery and Consumption

Inotropic and Vasopressor Drugs

Support of the Respiratory System

Antimicrobial Therapy

Proposed Therapies

Immunotherapy

Corticosteroids

Naloxone

Cyclooxygenase Inhibitors

Metabolic Manipulations

ESTABLISHED MULTIPLE ORGAN FAILURE

Prevalence

Prognosis

Etiology and Pathophysiology

Clinical Manifestations

Current Treatment Modalities

SUMMARY

*Formerly, Major, Medical Corps, U.S. Army; Staff Anesthesiologist, Staff Intensivist, Anesthesia and Operative Services, Walter Reed Army Medical Center,

Washington, D. C. 20307-5001; currently, Assistant Professor of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida 32608-1197; Codirector, Surgical Intensive Care Unit, Veterans Affairs Medical Center, P. O. Box 100254, Gainesville, Florida 32610-0254

†Lieutenant Colonel, Medical Corps, U.S. Army; Chairman, Pulmonary and Critical Care Service, Landstuhl Regional Medical Center (Landstuhl, Germany),

APO, AE 09180

THE SYNDROMES OF SYSTEMIC

INFLAMMATORY RESPONSE AND

MULTIPLE ORGAN DYSFUNCTION
Anesthesia and Perioperative Care of the Combat Casualty

598

INTRODUCTION

Sepsis is a systemic response to an infectious

process. An infection, usually caused by Gramnegative enteric bacilli, initially provokes a localized beneficial inflammatory response. However, if

bacteria invade the surrounding tissue (thus gaining access to the bloodstream) and elicit an acute

systemic inflammatory response by the host, myriad

organ and systemic dysfunctions, possibly culminating in death, can ensue. Gram-positive organisms usually associated with suppuration, viruses,

fungi, rickettsiae, and protozoa can also cause this

systemic response. It is the systemic response—especially when it is manifested by cardiovascular shock

and progressive, sequential dysfunction of multiple

organs—that differentiates bacteremia or localized

infection from sepsis. Diagnosis of an infection, however, may not be easy, as fever, leukocytosis, and a

hyperdynamic “septic” state may naturally occur

soon after injury.1 Furthermore, everyday clinical

use of words such as “infection” and “sepsis” does

not always make this distinction.

Compounding this semantic imprecision is the

confusion that the signs and symptoms themselves

introduce. The signs and symptoms seen when sepsis

is associated with bacterial infection are indistinguishable from those seen with noninfectious inflammatory states. Clinical conditions that mimic sepsis

include pulmonary atelectasis, pulmonary emboli,

hematomas, tissue necrosis, transfusion reactions,

myocardial infarction, hypotension or hypovolemia

from an ongoing occult hemorrhage, spinal shock,

central fever, or drug fever.1 Although infection

often occurs in patients with these conditions, the

conditions themselves must be considered as possible causes for a patient’s deteriorating condition.

Therefore, paradoxically, some patients seem to

have sepsis but no microorganisms can be cultured.

In an attempt to both address the paradox and

clarify the meaning of the constellation of terms

revolving around “sepsis,” the American College of

Chest Physicians and the Society of Critical Care

Medicine held a joint consensus conference in August 1991. The Textbook of Military Medicine uses

their recommended definitions and guidelines (Exhibit 24-1).2 The Consensus Conference introduced

a new term that provides an overall conceptual and

practical rubric: the systemic inflammatory response

syndrome (SIRS).

The relationship of SIRS to sepsis can be demonstrated in a Venn diagram that comprises three

overlapping populations (Figure 24-1): (a) infection, in which most of the population has neither

sepsis nor SIRS; (b) sepsis, which is a subgroup of

the infection population that by definition also has

SIRS; and (c) SIRS, which comprises both those with

sepsis and those in whom there is no apparent

infectious process. The Consensus Conference recommended that sepsis be defined as the clinical

condition that exists when the systemic inflammatory response state is due to infection, the most

common cause for SIRS. For this reason, the term

sepsis/SIRS will be used in this chapter.

The two most severe pathophysiological consequences of SIRS are septic shock (the most severe

circulatory derangement caused by sepsis) and

multiple organ dysfunction syndrome (MODS, the

sequential and progressive failure of two or more

organ systems). Although the terms “multiple system organ failure” and “multiorgan failure” are

also to be found in the literature, this chapter uses

MODS, the terminology adopted by the Consensus

Conference.

2 The term SIRS/MODS, which reflects

the intense relation of SIRS and MODS, will also be

used.3 MODS is most often associated with sepsis

(any diffuse inflammatory stimulus may act as the

initiating event), with a temporal relation to septic

shock (Exhibit 24-2 and Figure 24-2).

This definition and description of MODS should

not be applied to the casualty with multiple trauma

who has concomitant injuries to more than one

organ system. Such primary MODS should be distinguished from MODS that is secondary to sepsis/

SIRS with the concomitant release of endogenous

vasoactive mediator substances and is associated

with such systemic manifestations of sepsis as

hypotension and hypermetabolism.

EPIDEMIOLOGY

To understand the etiology and treatment of

SIRS/MODS, it is first necessary to understand the

circumstances in which it arises (ie, its epidemiology). The most extensive experience with this syndrome has been in civilian medicine, for not only is

that patient population much larger than the population encountered by military medicine, but the

conditions for providing care are much more suitable for making clinical observations. Furthermore,

the military experience with SIRS/MODS is epi-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

599

EXHIBIT 24-1

DEFINITIONS OF TERMS

Infection Microbial phenomenon characterized by an inflammatory response to the presence of

microorganisms or the invasion or normally sterile host tissue by those organisms.

Bacteremia The presence of viable bacteria in the blood.

SIRS Systemic inflammatory response syndrome; the systemic inflammatory response to a variety

of severe clinical insults. The response is manifested by two or more of the following

conditions:

(1) temperature > 38°C or < 36°C,

(2) heart rate > 90 beats per minute,

(3) respiratory rate > 20 breaths per minute or PaCO2< 32 mm Hg, or

(4) leukocyte count > 12,000 mm3, < 4,000/mm3, or > 10% immature (band) forms.

Sepsis The systemic response to infection; manifested by two or more of the following conditions as a result of infection:

(1) temperature > 38°C or < 36°C,

(2) heart rate 90 beats per minute,

(3) respiratory rate > 20 breaths per minute or PaCO2 < 32 mm Hg, or

(4) leukocyte count > 12,000 mm3, < 4,000/mm3, or > 10% immature (band) forms.

Severe Sepsis Sepsis associated with organ dysfunction, hypoperfusion, or hypotension. Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis,

oliguria, or an acute alteration in mental status.

Septic Shock Sepsis-induced, with hypotension despite adequate fluid resuscitation, along with the

presence of perfusion abnormalities that may include, but are not limited to, lactic

acidosis, oliguria, or an acute alteration in mental status. Patients who are receiving

inotropic or vasopressor agents may not be hypotensive at the time that perfusion

abnormalities are measured.

Sepsis-Induced A systolic blood pressure < 90 mm Hg or a reduction of > 40 mm Hg from

Hypotension baseline in the absence of other causes for hypotension.

MODS Multiple organ dysfunction syndrome; the presence of altered organ function in an acutely

ill patient such that homeostasis cannot be maintained without intervention.

Data source: Bone RC, Balk RA, Cerra FB, et al. The American College of Chest Physicians/Society of Critical Care Medicine

Consensus Conference Committee. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies

in sepsis. Chest. 1992;101:1644–1655.

sodic, depending on the random occurrence of wars.

Nevertheless, the military experience with sepsis/

SIRS has been of disproportionately great importance to understanding this syndrome: observations made by military physicians led to the initial

concepts of the renal and pulmonary components of

MODS.4,5

The Civilian Experience

Sepsis/SIRS and the related pathological conditions of septic shock and MODS occur in 5 to 10 of

every 1,000 hospitalized patients; the rate for patients admitted to intensive care units (ICUs) is

increased by 10-fold.6,7 This equates to 100,000 to

500,000 new cases per year in the United States,

with 70,000 to 300,000 cases per year arising from

Gram-negative infections alone.6,8 Of these, approximately 200,000 will develop septic shock with

a mortality rate of about 50%.8 The prevalence of

SIRS/MODS appears to be increasing as a consequence of (a) the population of patients now receiving treatment and (b) advances in medicine; for

example,6

• the care being given to an ever-increasing

aged population with their associated

chronic diseases;
Anesthesia and Perioperative Care of the Combat Casualty

600

Fig. 24-1. In this Venn diagram showing the interrelation

of infection, sepsis, and the systemic inflammatory response syndrome (SIRS), the large circle represents the

population with infection and the small circle represents

the population with SIRS. The intercept—sepsis—represents the subpopulation who have both infection and

SIRS. Note that some patients with SIRS do not have

sepsis. Data source: Bone RC, Balk RA, Cerra FB, et al.

The American College of Chest Physicians/Society of

Critical Care Medicine Consensus Conference Committee. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest.

1992;101:1645.

Fig. 24-2. This Venn diagram represents the interrelation

of sepsis, septic shock, and multiple organ dysfunction

syndrome (MODS). By definition, all patients with septic

shock have sepsis, but not all patients who develop

MODS have sepsis as the etiology.

• the numbers of immunocompromised patients (steroidal or chemotherapy, transplantation, human immunodeficiency virus [HIV] disease) now receiving care;

• the widespread use of antibiotics with subsequent development of resistant bacterial

strains,

• an increased number of patients surviving

severe trauma; and perhaps

• the sophistication, increased invasiveness,

and aggressive use of current medical diagnostic procedures, interventions, and treatments.

The Military Experience

During peacetime, the epidemiology of sepsis

and its related conditions is the same in the civilian

and military healthcare systems with the important

distinction that the military population consists of

young, healthy individuals who are less likely to

become ill compared to the civilian population as a

whole. During wartime, injuries and diseases that

may predispose to the development of sepsis have

a high prevalence. In U.S. Army, attrition (as assessed by hospital admissions) has been due predominantly to disease and nonbattle injury and not

due to injury that resulted from combat. The ratio

of admissions to admissions for combat-related injuries ranged from 16:1 during World War I to 88:1

during World War II.9 Most of these admissions

were for relatively minor illnesses and injuries that

EXHIBIT 24-2

KNOWN ETIOLOGY OF SEPSIS/SIRS

Microbial Agents

Bacteria

Viruses

Fungi, protozoa, rickettsiae, etc

Gram-Negative Bacterial Component

Endotoxin

Tissue Inflammation Caused by

Multiple trauma

Pancreatitis

Long-bone or pelvic fractures

Aspiration pneumonitis

Adult respiratory distress syndrome

Tissue Hypoperfusion

Distributive shock

Infection Sepsis

Sepsis Septic Shock

Multiple

Organ

Dysfunction SIRS Syndrome
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

601

occurred outside the combat zone and rarely progressed to a septic state.

In contrast to the 18th and 19th centuries, death

due to septic consequences of disease and nonbattle

injuries has been less common during the 20th century. However, given special circumstances such as

the influenza pandemic of 1917 to 1919, sepsis can

be the leading cause of mortality. For example, of

the 3,264,694 enlisted personnel who were admitted

to the hospital for disease from April 1917 through

December 1919 in the United States and Europe,

51,447 died of disease compared with 50,385 deaths

caused by combat.10–12 The most common sepsisrelated disorders causing death during this period

(1917–1919) included general septicemia, bronchoand lobar pneumonia, and suppurative pleurisy.11

Although disease-related death rates have decreased

in subsequent wars, diseases accounted for a large

proportion of all U.S. Army hospital admissions

during the Vietnam War (1965–1970): from a high of

74% in 1965 (when diseases accounted for 5,697 of

7,682 hospitalizations) to a low of 56% in 1968 (when

diseases accounted for 51,082 of 91,417 hospitalizations).12,13

Traumatic Injury

Traumatic battle injuries pose a major threat to

combat forces—vastly greater than anything seen

in the civilian experience. Severe injuries often

result in death. On the basis of the civilian experience with trauma, it is possible to categorize deaths

from injury into three categories, based on the time

of death in relation to the time of injury. Immediate

deaths are caused by massive trauma, aortic rupture, decapitation, and so forth. These can only be

prevented by measures designed to prevent trauma

(eg, public safety measures, safer cars and airplanes).

Early deaths occur during the first hour following

injury and are caused by posttraumatic conditions

such as hypovolemic shock or tension pneumothorax. These conditions can be effectively managed only by individuals or institutions capable of

providing early interventions and therapy. (It is

this category of deaths that has been the focus of the

Advanced Trauma Life Support Course sponsored

by the American College of Surgeons.) Late deaths

occur during the first week after traumatic injury.

Two major causes are irreversible brain injury and

sepsis.14,15 The civilian experience has been that

from one third to one half of all trauma deaths fall

in the late category. SIRS/MODS progressing to

organ failure is important for anesthesiologists and

critical care specialists to understand because

• the syndrome is a major cause of death

from civilian trauma,

• the potential for live-saving intervention is

real, and

• the need to develop effective means of prevention and treatment cannot be overemphasized.

The potential that combat-related deaths can be

reduced through improved prevention and management of SIRS/MODS is less favorable. In contrast to the civilian experience, most combat-related

deaths (70%–80%) are early (this is the category

called killed in action) and only about 10% of the total

fatalities occur during treatment in a hospital (died

of wounds). By far most combat deaths are due to

hemorrhage or mutilating brain injury.16 This population does not live long enough to develop sepsis.

SIRS/MODS is the cause of death in about one third

of those who die while being treated (or perhaps 5%

of all fatally wounded soldiers).

Trauma-Related Sepsis and Septic Shock

The traumatized combat victim is at great risk for

developing sepsis. A civilian study of 437 trauma

patients who sustained both blunt and penetrating

injuries revealed that more than three fourths of

deaths that occurred after 7 days resulted from

sepsis and MODS.15 In another study, almost 90% of

deaths after 7 days in patients sustaining blunt

trauma were shown to be related to sepsis.17 And in

patients sustaining thermal injury or trauma, at

least 75% of deaths may, in part, be due to sepsis.18

Military data on posttraumatic sepsis are best

delineated in statistics describing the U.S. Army’s

experience in World War II and the Korean and

Vietnam Wars. The decrease in the died-of-wounds

rate—from 8% in World War I to the overall 4.5%

recorded in World War II—has been attributed to

the prevention of sepsis in extremity wounds by

earlier and more extensive surgery. As expected,

shock and hemorrhage were the major causes of

death among the hospitalized wounded, followed

by infection (especially in the peritoneal cavity).

Other cases of unrecognized sepsis may well have

occurred in those patients whose cause of death was

described as myocardial failure, anuria, pulmonary

edema, or atelectasis.19

The incidence of true septic shock was not described outside these categories. However, in 1944

in the Fifth U.S. Army, the deaths of 1,273 hospitalized soldiers were attributed to shock. Of these,

34% resulted from trauma and hemorrhage in asso-
Anesthesia and Perioperative Care of the Combat Casualty

602

ciation with documented sepsis. An additional 22%

might appropriately be included: those patients

without recognized sepsis but who had, in addition

to trauma and hemorrhage, what was then called

cardiorespiratory embarrassment.19 The severity

and complexity of combat-related wounds, then,

portends a particularly significant risk for the development of infection and sepsis. MODS and eventual death are common among those who sustain

severe war wounds and who survive long enough to

reach a medical treatment facility. The U.S. Army’s

most recent extensive experience was during the Vietnam War. Data on the causes of hospital deaths show

that sepsis and its complications probably caused

about one third of the deaths (Figure 24-3).20

Most individuals deployed for possible combat

are relatively young and healthy. Thus, soldiers

generally do not have the medical illnesses that

predispose to the development of sepsis (eg, diabetes mellitus, hepatic cirrhosis, chronic renal insufficiency, underlying malignancies, and inherited or

acquired immunological defects).21,22 But larger

mobilizations that employ personnel not on active

duty will most certainly include individuals whose

underlying illnesses will become manifest. Illnesses

acquired during military operations, principally

infectious diseases such as malaria, will alter the

host’s immunoregulatory function in such a way

that bacterial sepsis may be likely to occur. The

fatigue, stress, and loss of sleep associated with

combat maneuvers may also be associated with an

increased incidence of infection.23

As trauma management continues to improve,

more patients remain alive 2 or 3 days after injury.

Infection during these first several days is rare, but

increases in prevalence thereafter. Most cases of

SIRS/MODS in the military will occur in casualties

with multiple injuries whose infectious complications are caused by some or any of the following

predisposing factors:

1. contaminated, open injuries (ie, penetrating thoracic or abdominal wounds, open

fractures, or burns), which have a high

propensity for infection and the subsequent systemic responses; for example,

penetrating abdominal trauma results in

an infection rate of 14% in patients without hemorrhagic shock (among patients

with hemorrhagic shock, the infection rate

increases 2- to 2.5-fold)24;

2. depression of both the humoral and the

cell-mediated immune systems, which

traumatic injury causes1

;

3. compromised host defenses, which can be

caused by medications such as steroids

and the use of parenteral nutrition1; and

4. transfused blood products, which can

spread such viral infections as hepatitis B

and C, as well as HIV.1

Prolonged stay in an ICU increases the incidence

of nosocomial infections as a consequence of the use

of endotracheal tubes, intravascular and in-dwelling urinary catheters, and other monitoring and

support systems. Therapies including hyperalimentation, antibiotics, and dialysis also contribute

to the development of infection because normal

Hospital Deaths

 1,253

Medical

 91

Surgical 

 1,162

Septic Shock

 136

Hemorrhage

 278

Burns

 35

Respiratory

 71

Head Injury

 494

Miscellaneous

 148

Fig. 24-3. The causes of death for 1,253 casualties who were hospitalized in Vietnam in 1969. The “miscellaneous”

category includes entries such as fat embolism, 24; acute renal failure, 15; quadriplegia, 15. Data source: Arnold K,

Cutting RT. Causes of death in United States military personnel hospitalized in Vietnam. Milit Med. 1978;143:161–164.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

603

skin and mucosal physical barriers to infection are

broken by these devices. Contamination of these

devices during insertion or use can also result in

superinfection.25

As a consequence, after 3 days in a surgical ICU,

50% of patients become colonized with potentially

pathogenic bacteria, and by 10 days, 95% of patients

acquire new flora.26 In a study done between 1977

and 1984 at the Shock Trauma Center, Maryland

Institute for Emergency Medical Services Systems

(MIEMSS) in Baltimore, Maryland, 1,407 patients

(14% of total admissions) developed 2,310 documented infections.1 Among trauma patients who

survived their initial injury, 22% to 63% developed

one or more infections, with a 41% to 65% mortality.

Once the patient contracted an infection, the duration of stay in the ICU increased from 7.4 to 13.5

days. The five leading infections in this study were,

in order of frequency, urinary tract infections, pneumonia, surgical-wound infections, phlebitis, and

intraabdominal infections. Patients with pneumonia or intraabdominal infection had mortality rates

of 29% and 25%, respectively.1

 Most nosocomial

infections in surgical patients occur in the urinary

tract, the surgical wound and skin, and the respiratory tract.27 Tabulated data from 82 hospitals show

the frequencies of these infections to be 39%, 32%,

and 16%, respectively.28 The causative organisms

vary somewhat with the location. Across all services (medical and surgical), Escherichia coli is the

most prevalent pathogen and Staphylococcus aureus

the second most common. The second most prevalent pathogen on medical and general surgical services alone is Pseudomonas aeruginosa. (Enterococcus

is the second most common on gynecological and

obstetrical services.25)

Infections in trauma patients were well described

in the MIEMSS study. The most frequent pathogens

were S aureus (25%), E coli (13%), P aeruginosa (10%),

Enterobacter species (10%), and Klebsiella species

(9%). Gram-positive cocci were causative alone

or partially involved in 43.9% of the infections,

Gram-negative bacilli in 66.8%, anaerobic bacteria

in 9.3%, and yeast in 1.5%. Nationwide, the pathogen most frequently found in the traumatized patient is S aureus.

1

The true incidence of sepsis resulting from trauma

is difficult to glean from the literature. At MIEMSS,

of the more than 10,000 patients admitted during

the study period, 1,407 developed 2,310 infections,

900 (39%) of which were documented cases of

bacteremia.1 The mortality rate of patients with

bacteremia was 21%. Additional studies reported

an 8.3% incidence of sepsis with bacteremia in 300

trauma patients,29 and a 17% incidence in 200 patients.30 Thus among trauma patients, the incidence of

bacteremia with subsequent sepsis is 10% to 20%.1

Other sources of bacteremia in trauma patients in

the MIEMSS study include vascular infections (22%),

pneumonias (14%), intraabdominal infections (10%),

empyemas (9%), and wound infections (8%). The

vascular infection rate may have been underestimated, as it is only a recent practice to culture the

tips of intravenous lines. An additional 21% of

cases were without a definite source.1

The organisms resulting in bacteremia were similar to those causing all diagnosed infections. Staphylococcus aureus was the most common, resulting

in 35% of the cases of bacteremia. Others were

Klebsiella (12%), Enterobacter (10%), Pseudomonas

aeruginosa (8%), and Escherichia coli (9%).1

Microbes in the bloodstream are the consequence

of, or perhaps lead to the development of, overwhelming infection. Two separate complications

arise from the systemic circulation of microorganisms31:

1. Organisms are seeded throughout the

body, with subsequent formation of microscopic or even macroscopic abscesses.

2. A systemic effect occurs as a consequence

of the mere presence of the organism or

organism components (eg, the cell wall) in

the bloodstream. This activates a cascade

of inflammatory and endocrinological

events that produce the systemic deterioration seen in sepsis, the final stage of

which is septic shock.

Cellular and Subcellular Mechanisms Leading

to SIRS/MODS

SIRS/MODS is now believed to result from the

patient’s systemic response to the growth of microorganisms at what is initially a localized site of

infection (the nidus). Various components of microorganisms (eg, the cell wall), or substances elaborated by microorganisms (eg, toxins) are now

thought to provoke the cellular components of blood

(eg, monocytes and neutrophils) that are responsible for the normal immune response. The normal

immune response results in the formation of endogenous mediators, which, if overproduced, have

many deleterious pathophysiological effects (eg,

myocardial depression and peripheral vascular vasodilation). Shock, MODS, and possible death then

ensue.32 Figure 24-4 is a schematic representation of

this sequence of events.
Anesthesia and Perioperative Care of the Combat Casualty

604

Nidus of Infection Organism 

Endogenous Mediators 

Myocardium 

Refractory

Hypotension

Multiple Organ

Failure 

Death or Recovery 

Components of or Products 

from Proliferating 

Microorganisms 

Shock 

Blood Cells 

Vasculature Organs 

Fig. 24-4. Schematic showing important steps by which

infection can cause shock, multiple organ failure, and

death. Endogenous mediators released from normal cellular constituents of the blood play a crucial role. Adapted

with permission from Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993;328:1472.

cardiotoxin of diphtheria, and the various histotoxins produced by species of Clostridium. These

toxins, which are secreted by Gram-positive bacteria, are polypeptides with specific tissue targets. In

contrast, endotoxins (literally, toxins from within)

are normal constituents of the cell wall of Gramnegative bacteria; they are injurious to humans in

the clinical setting that we now recognize as sepsis/

SIRS. In fact, the most widely studied triggering

event for sepsis/SIRS is the presence of endotoxin.

Endotoxin, from inside to outside the cell wall,

comprises Lipid A, the core polysaccharide, and the

O Antigen (Figure 24-5). In addition, endotoxin has

one chemically unique constituent, the strange sugar

molecule Kdo (3-deoxy-D-manno-2-octulosonic

acid), which is found in all endotoxins and links the

core polysaccharide to lipid A.33 It is important to

recognize that the peptidoglycan/teichoic acid complex of the cell wall of Gram-positive organisms, as

well as the polysaccharide constituents of certain

yeasts, have toxicity similar to that of endotoxin. As

Lewis Thomas described in 1974, endotoxin is not

only a strange substance chemically, it also provokes a violent and frequently self-destructive response in humans and other animals:

Our arsenals for fighting off bacteria are so powerful, and involve so many different defense mechanisms, that we are in more danger from them than

from invaders. We live in the midst of explosive

devices; we are mined.

It is the information carried by the bacteria that we

cannot abide.

The gram-negative bacteria are the best examples

of this. They display lipopolysaccharide endotoxin

in their walls, and these macromolecules are read

by our tissues as the very worst of bad news. When we

sense lipopolysaccharides, we are likely to turn on

every defense at our disposal; we will bomb, defoliate, blockade, seal off, and destroy all tissues in the

area. Leukocytes become more actively phagocytic,

release lysosomal enzymes, turn sticky, and aggregate together in dense masses, occluding capillaries and shutting off the blood supply. Complement

is switched on at the right point in its sequence to

release chemotactic signals, calling in leukocytes

from everywhere. Vessels become hyperreactive to

epinephrine so that physiologic concentrations suddenly possess necrotizing properties. Pyrogen is

released from leukocytes, adding fever to hemorrhage, necrosis, and shock. It is a shambles.

All of this seems unnecessary, panic-driven. There

is nothing intrinsically poisonous about endotoxin,

but it must look awful, or feel awful, when sensed

by cells. Cells believe that it signifies the presence

of gram-negative bacteria, and they will stop at

nothing to avoid this threat.34(p92)

Components of, or Products

From, Proliferating

Microorganisms

By emphasizing the primacy of the host response,

this paradigm advances our understanding of the

origins of the deleterious consequences of sepsis.

The immune system, which normally protects the

host, releases endogenous mediators as part of its

“normal” inflammatory response to infection. Such

detrimental phenomena as cell and organ damage

and death seem to result from the immune system’s

hyperresponsiveness to the insult.

Components and Products From Microorganisms

Giving Rise to SIRS/MODS

The most notorious toxins produced by microorganisms include the neurotoxin of food-borne botulism, the neurotoxin that causes tetanus, the
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

605

b

a

c

Fig. 24-5. The cell membrane of a Gram-negative bacterium, diagrammed at successively higher magnifications. (a)

The cell wall, composed of two layers of lipids. (b) Endotoxin in its normal position in the outer membrane. (c) The

chemical composition of the endotoxin. There are two important moieties: (1) a polysaccharide known as the O-chain

and (2) a fat called lipid A. Several sugar molecules of unusual composition are found at the polysaccharide–lipid A

junction. Lipid A, together with the sugar 3-deoxy-D-manno-2-octulosonic acid, is the portion of the endotoxin

molecule that is responsible for its pathophysiological effects. Reprinted with permission from Rietschel ET, Brade H.

Bacterial endotoxins. Sci Am. 1992;August:56, 57.

Until recently, data had been accumulated only

from animal studies, but prospective assays reported in 110 patients with shock show a 43% incidence of endotoxemia in septic shock, compared

with a 10% incidence in shock from other causes.35

Patients who had endotoxemia developed organ

failure 10-fold more frequently than other patients,

indicating that the damaging role of this compound

is significant.

Cellular Components Contributing to SIRS/MODS

It is now generally agreed that endotoxin by

itself is not the direct cause of the pathophysiology of sepsis/SIRS. Rather, its effect is mediated

through a variety of cells both in the blood and in

tissue.

Mononuclear Cells

The mononuclear phagocyte system is composed

of (a) bone marrow–derived monocytes that circulate in the blood stream and (b) tissue macrophages

such as the hepatic Kupffer cells and pulmonary

alveolar macrophages.36,37 These blood and tissue

macrophages appear to be the essential cellular

components required for the development of sepsis

and SIRS/MODS. As part of the inflammatory

process, resting macrophages exposed to stimuli

such as T cell–produced interferon gamma (IFN-γ)

Cell

Membrane

Chemical structure
Anesthesia and Perioperative Care of the Combat Casualty

606

or lipopolysaccharide (endotoxin) from Gram-negative–organism cell walls are activated into larger,

more metabolically active cells. These activated

macrophages secrete lysozyme, proteases (collagenase and elastase), plasminogen activator, interleukin-1 (IL-1), various leukotrienes, and cytokines

such as tumor necrosis factor (TNF).34

Polymorphonuclear Cells

An interaction occurs between activated macrophages and polymorphonuclear leukocytes

(PMNs). Human alveolar macrophages, and perhaps others, secrete a neutrophil activating factor

that appears to enhance the PMNs’ bactericidal

activity by causing a greater release of superoxide.

This interaction likely contributes to further hosttissue damage and inflammation.36

Protection of the host against many infections

depends greatly on both the absolute number and

the functions of PMNs, including chemotaxis,

adherence, phagocytosis, and the eventual destruction of the ingested microorganism.36 It is

during the killing of the phagocytized organisms

that the neutrophil may release substances that are

toxic to the host, resulting in injury to the host (the

patient).

Polymorphonuclear adherence to vascular endothelial sites (leukostasis) contributes to vascular

injury in inflammation, particularly in the lung, and

may also explain the initial neutropenia noted in

some patients with sepsis.36,38–40 To be effective, the

PMNs must act at the site of microbial invasion.

Chemotaxis or directed migration to the inflammatory nidus occurs in response to many agents, including oligopeptides produced by the invading

organism, complement factor C5a induced by both

the organism and the accumulated neutrophils, and

leukotriene B4 produced by on-site neutrophils.37

After the neutrophil’s phagocytosis, a respiratory

burst within the PMN contributes to the inflammatory response in the following three ways:

1. The increased oxygen consumption of this

respiratory burst is associated with the

increased production of lethal oxidants

(superoxide anion, hydrogen peroxide,

hypochlorous acid, the hydroxyl radical,

and the hydroxyl anion).

2. Lipid metabolism results in the production of thromboxane, leukotrienes, platelet activating factor, and leukotoxin.

3. The PMN degranulates.

The inflammatory process in the host is activated

and propagated by these mechanisms. The various

mediators released by the neutrophil, in particular

the oxygen radicals, are not specific for foreign

antigens. Thus the host tissues are susceptible to

the toxic effects of these substances. This is a major

factor in the adverse response to infection.

In the adult respiratory distress syndrome

(ARDS), the abundance of neutrophils retrieved

from a bronchoalveolar-lavage sample is evidence

for the central role that neutrophils play.41 In contrast, few neutrophils are recovered from bronchoalveolar lavage in patients with non-ARDS respiratory failure. Abundant neutrophils are a component

of syndromes other than ARDS, however: ARDS

can also occur in neutropenic patients. Neutrophils

in the pulmonary circulation have been shown to

release several harmful byproducts (eg, collagenase, myeloperoxidase, and elastase) that may cause

systemic injury.

Lymphocytes

Specifying the host’s immunological response to

invading pathogens is the role of the lymphocyte.

The full response requires an extensive interaction

between these lymphocytes and macrophages. Lymphocytes are subdivided into T lymphocytes, which

make up 70% of all mononuclear cells, and B lymphocytes, which, along with natural killer cells and

monocytes, comprise the remaining 30%.42

T lymphocytes direct cell-mediated immunity in

the host and exist in two forms:

1. helper/inducer or cluster of differentiation (CD) 4+ cells, which enhance the host’s

immunological response by supporting TT cell, T-B cell, and lymphocyte–macrophage interactions; and

2. suppressor or CD8+ cells, which inhibit B

cell–antibody production and, hence, diminish immunological function.

Antibody-mediated (humoral) immunity is governed by the differentiation of B lymphocytes into

plasma cells that are capable of secreting antibodies. Antigens processed by the macrophage are

presented to B cells specific for that particular antigen, based on the antigen binding site (Fab segment) on the B lymphocyte’s membrane-bound

immunoglobulin. The degree of B cell and plasmacell clonal expansion is controlled by helper and

suppressor T cells.43
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

607

Macrophages are known to interact with both T

and B cells at inflammatory sites. An interaction

between T cells and the macrophage causes the T

cell to secrete lymphokines (eg, IFN-γ, macrophage

inhibitory factor, monocyte chemotactic factor, IL2) and the macrophage to release monokines (including IL-1 and TNF).37 These lymphokines also

modulate the host’s immunological response by

their effects on other lymphocytes, macrophages,

neutrophils, and invading organisms.43

Endogenous Mediators

Much of the current experimental and clinical

research is directed toward finding the endogenous

mediators produced by cells that link such pathophysiological derangements as septic shock and

MODS to microorganisms and their endotoxins.

The two leading candidates at present are a group

of small-molecular-weight proteins known as

cytokines and the eicosanoid metabolites of arachidonic acid.

Cytokines: Tumor Necrosis Factor and the

Interleukins

TNF (also called cachectin)—a small polypeptide

protein with a molecular weight about 17,000—is

released when endotoxin stimulates blood or tissue

macrophages, endothelial cells, and lymphocytes.

Its effects include

• enhancement of the immune system,

• hypotension due to a decrease in peripheral vascular resistance,

• loss of fluid from the vascular bed (caused

by an increase in both the systemic and

pulmonary capillary permeability),

• a variety of metabolic changes (eg, lipolysis

and increased amino acid loss from skeletal

muscle), and

• the long-term acceleration of wound healing.

Many of these changes are virtually identical to

those observed with endotoxin, including fever,

shock, and lactic acidosis. Several studies have identified a prime role for TNF in clinical sepsis or MODS:

• Intravenous injection of human recombinant TNF into laboratory rats44 and dogs45

results in hypotension, shock, metabolic

acidosis, and death due to respiratory arrest within hours. Autopsy showed many

of the same findings seen in patients who

had died of MODS.46

• The administration of monoclonal antibodies to TNF almost completely prevents obvious organ injury in most animal models

of septic shock including those in which

endotoxin is also administered.47

• TNF produces myocardial cell dysfunction

in an animal model48 and may be the substance responsible for myocardial depression in human sepsis/SIRS.49

Studies on humans with sepsis have begun to provide support for the paradigm that views TNF as

the proximate cause of SIRS:

• Serum levels of TNF are significantly higher

in patients with sepsis who ultimately developed septic shock, compared with patients who did not develop shock.50

• Patients who died of sepsis within 25 hours

of starting treatment for septic shock had

TNF levels nearly 20-fold greater than those

who die later.50

• TNF production from monocytes taken from

trauma victims correlated with septic episodes.51

Interleukin-1 and Interleukin-2

IL-1, which can be thought of as an endogenous

pyrogen, is classified as a monokine, which is produced when a macrophage is stimulated by bacteria. The effects of this mediator include hypothalamic stimulation, producing fever, leukocytosis,

an increase in the hepatic acute-phase reactants (eg,

C-reactive protein), and an increase in muscle proteolysis. An intravenous infusion of IL-1 in laboratory animals results in the hemodynamic appearance of septic shock. The exact contribution of IL-1

in the pathophysiology of MODS is unknown.

IL-2 is a macrophage product that has been administered to patients with metastatic cancer as

part of immunotherapy. Administration of IL-2

causes hemodynamic changes that mimic the sepsis

syndrome. Furthermore, case reports have described

patients who developed organ failure during immunotherapy with IL-2.52,53

Eicosanoids: The Arachidonic Acid Metabolites

Eicosanoid is the generic term for the leukotriene,

prostaglandin, and thromboxane metabolites of
Anesthesia and Perioperative Care of the Combat Casualty

608

Fig. 24-6. The origin and partition of several biologically

important eicosanoids. Note that arachidonic acid can be

acted on by two enzymes: (1) lipoxygenase, which gives

rise to the leukotrienes, and (2) cyclooxygenase, which

gives rise to thromboxane, prostacyclin, and prostaglandin

E2, which have markedly different physiological effects.

arachidonic acid (a polyunsaturated fatty acid). For

the most part, they are potent but short-lived molecules produced by all nucleated cells anywhere in

the body. Endothelial cells, macrophages, and platelets produce eicosanoids in areas where microorganisms have invaded tissue, a feature that is of

special importance to the study of sepsis.

Given any number of stimuli such as hypoxia,

damaged vascular endothelium, and especially the

liberation of cytokines, free arachidonic acid is liberated from the phospholipid component of the cell

membrane, from which it diffuses into the cytosol.

Depending on the cell type, arachidonic acid becomes the substrate for one of two enzymes:

lipoxygenase or cyclooxygenase (Figure 24-6).

Lipoxygenase catalyses the formation of the

leukotriene eicosanoids, while cyclooxygenase

forms multiple eicosanoids, of which the most important are thromboxane A2, prostacyclin (prostaglandin I2), and prostaglandin E2.

Of the myriad biological effects associated with

eicosanoids, the effects most likely to be relevant to

our understanding of sepsis/SIRS are those caused by

• the leukotrienes, which cause alterations of

neutrophil function leading to increased

chemotaxis, synthesis of the superoxide

anion radical, increased microvascular permeability, vasoconstriction, and bronchoconstriction;

Leukotrienes Intermediate Form

(myeloid cells)

Prostacyclin

(endothelium)

Prostaglandin E2

(CNS)

Thromboxane

(platelets)

Arachidonic Acid

Lipoxygenase Cyclooxygenase

Phospholipid in Cell Membrane

• thromboxane, which causes platelet aggregation and vasoconstriction;

• prostacyclin, which causes platelet disaggregation and vasodilation; and

• prostaglandin E2, which causes intensive

pulmonary and systemic vasodilation,

hyperalgesia, and fever.

The leukotrienes have the ability to cause many

of the pathophysiological changes that are seen in

sepsis/SIRS. However, there are two reasons why

the eicosanoids produced by the lipoxygenase pathway are less likely to be important than those produced by cyclooxygenase:

1. The enzyme lipoxygenase is present only

in myeloid cells, whereas cyclooxygenase

is present in all cells.

2. Lipoxygenase, in contrast to cyclooxygenase, is normally inactive and needs to

be “turned on” before any eicosanoids are

produced.

Several lines of evidence support the role of the

cyclooxygenase metabolic products of arachadonic

acid in the development of sepsis/SIRS. Putative

reasons for the involvement of phospholipids as

endogenous mediators of sepsis/SIRS have been

the subject of considerable research.54 Many of the

signs and symptoms of sepsis/SIRS such as fever

and shock can be replicated by eicosanoids. For

example, elevated levels of thromboxane B2 have

been measured in patients with sepsis, but whether a

cause-and-effect relationship exists is unclear at

present. Some of these findings include the following:

• There is less hemodynamic compromise

and increased survival when thromboxane

is inhibited.55

• In human volunteers, ibuprofen lessens the

signs and symptoms associated with endotoxin administration.56

• Ibuprofen normalizes hemodynamic indices in dogs with experimental sepsis.57

• Pulmonary permeability edema decreases

in a large-animal sepsis model using

ibuprofen to inhibit the cyclooxygenase

pathway.58

Prostacyclin, because of its strong vasodilator

properties, may be the mediator of the peripheral

vasodilation seen in most cases of human septic

shock—although why its effect should predomi-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

609

molecular orbitals. Their chemical activity is markedly heightened compared with molecules with

paired outermost electrons. Most free radicals are

derived from oxygen (a not-unsurprising situation

given the prominence of oxygen in our environment and our dependence on oxygen for the energy-producing processes necessary for life). Nearly

all the oxygen that enters into the normal mitochondrial production of adenosine triphosphate is converted to water by the near-simultaneous addition

of four electrons. However, in a process known as

the univalent leak, about 1% of the oxygen molecules

normally undergo a four-step reduction that involves the addition of one electron at a time. Each

time an electron is added, a different type of oxygen-derived free radical is formed. These are, in

order of their generation: the superoxide anion radical (O2•), the hydroperoxyl radical (HO2•), hydrogen peroxide (H2O2), and the hydroxyl radical

(OH•). Although hydrogen peroxide itself is not a

free radical, it is rapidly converted into the

hydroperoxyl and hydroxyl radicals.

Mammalian cells normally contain substances

with strong antioxidant properties, of which the

enzymes superoxide dismutase and catalase are best

known; these enzymes prevent the intracellular accumulation of the toxic free radicals. Superoxide

dismutase catalyzes the conversion of the superoxide anion radical to hydrogen peroxide, while

catalase catalyzes the conversion of hydrogen peroxide to water. When these antioxidants function

properly, they prevent the generation of the

hydroperoxyl and hydroxyl radicals and thereby

minimize the potential for oxygen-derived freeradical injury.

Superoxide dismutase and catalase effectively

minimize oxygen-derived free-radical injury except

in two circumstances: the first is during the

reperfusion phase, when blood flow is normalized

following shock, ischemia, or hypoxia; the second,

paradoxically, is when neutrophils are activated as

part of their normal function (ie, they display their

respiratory burst). The generation of free radicals

presumably evolved for a beneficial purpose: the

destruction of foreign objects such as bacteria by

phagocytic cells. Neutrophils and macrophages

have on their cell membranes a liberal amount of

the enzyme nicotinic acid diphosphohydrogen oxidase,

which, when activated by any of several endogenous mediators such as TNF, generates superoxide anion radicals and hydrogen peroxide. At the

same time, the enzyme myeloperoxidase is released

by the cell and catalyses the formation of hypochlorous acid from hydrogen peroxide and chloride

nate over that of its antagonist, thromboxane, is

unclear.

The ability of prostaglandin E2 to cause hyperpyrexia relates to its direct effect on the thermoregulatory center in the hypothalamus. The activity of

the enzyme cyclooxygenase is decreased by drugs

that contain or are metabolized to salicylic acid (eg,

aspirin). The antipyretic action of aspirin depends

on its ability to decrease the formation of prostaglandin E2. The same mechanism—inhibition of

cyclooxygenase—explains the analgesic effects of aspirin: prostaglandin E2, which is known to sensitize

nerve endings to noxious stimuli, is not produced.

Unfortunately, the most recent and methodologically valid study of the role of eicosanoids in humans with severe sepsis failed to show a clear-cut

advantage from pharmacologically blocking the formation of eicosanoids with the nonsteroidal

antiinflammatory drug ibuprofen. Although fever,

blood pressure, heart rate, and oxygen transport

were at least partially normalized in the treated

patients, the researchers found no decrease in mortality compared with control patients.59 These negative findings suggest that the cascade of mediators

causing systemic response and sepsis is so complex

that blockade of only one component will not result

in improved patient survival.

Endorphins

A role in the pathogenesis of sepsis/SIRS for

endogenous opioids, of which β endorphin is the

best known, was first proposed in 1977 by researchers at Walter Reed Army Institute of Research, Walter

Reed Army Medical Center, Washington, D. C.

Naloxone, an antagonist of β endorphin, was shown

in a rat model to reverse the hypotension that was

caused by endotoxin.60 Significant species differences exist; in baboons, for example, hypotension

from endotoxin is not reversed by naloxone.61 Studies in which naloxone is given to humans with

septic shock have shown transient reversal of

hypotension but no effect on survival.62,63 Even

though β endorphin levels rise with trauma,64 the

attention paid to endogenous opioids in the pathogenesis of septic shock should probably be minimized, because these substances do not give rise to

the hyperdynamic and vasodilated state that characterizes human septic shock.

Free Radicals

Free radicals are chemical entities that contain

one or more unpaired electrons in their outermost

–
Anesthesia and Perioperative Care of the Combat Casualty

610

ions in the cell’s neighborhood. Hypochlorous acid

kills bacteria. The effect is twofold: not only does

the neutrophil’s respiratory burst produce lethal

oxidants, but it also contributes to the inflammatory

response by generating thromboxane, leukotrienes,

platelet activating factor, and leukotoxin.

Increasingly, the generation of oxygen-derived

free radicals in shock, ischemia, and hypoxia is believed to be a major source of the injury that characterizes these conditions. Although all constituents of a

cell are at risk, the lipid-containing membranes appear to be especially sensitive to destruction because

of the self-propagating nature of free-radical attack

on the polyunsaturated fatty acid portion of the cell

wall. Reaction of a free radical with a polyunsaturated fatty acid not only chemically alters the fatty

acid but also generates new free radicals—lipid

peroxides—that incorporate into parts of the original fatty acid. Two different free-radical attacks are

possible. First, the hydroperoxide pathway generates

two free radicals for every lipid molecule destroyed.

Second, the endoperoxide pathway generates three

free radicals. Thus, rapid dissolution of cell membranes occurs in a process reminiscent of the chain

reaction that characterizes atomic fission.

Nonoxygen-derived free radicals may also play a

role in the pathophysiology of sepsis/SIRS. One of

the most significant recent advances in vascular

physiology is the recognition that normal vascular

endothelium produces a potent vasodilator. This

was subsequently shown to be nitrogen monoxide

in one or more of its three forms: the free radical

nitric oxide (NO•), the nitrosonium cation (NO+) or

the nitroxyl anion (NO–).65 The vasodilator property of TNF has been shown to be dependent on the

presence of normal vascular endothelial cells, suggesting that nitric oxide may be the proximate cause

of the hypotension associated with sepsis.66 In fact,

high concentrations of the metabolites of nitric oxide have been described in patients with clinically

apparent sepsis, but not in trauma patients or controls who did not have sepsis. Furthermore, the

concentrations of these metabolites was inversely

related to the peripheral vascular resistance.67 These

data suggest that increased production of nitric

oxide may be a causative factor in the development

of septic shock. Specific blockers of the generation

of nitric oxide have been tried in patients in septic

shock.68 Although the patients’ hypotension was

ameliorated, their survival was not enhanced (which

is not too surprising given that hypotension by

itself is one of the several derangements that occur

in septic shock).

Additional Mediators

Complement. The alternate pathway of complement is known to be activated by endotoxin and

other bacterial products. The resultant release of

C3a and C5a leads to neutrophil stimulation and the

following adverse effects, which are seen in patients with sepsis/SIRS:

• increased vascular permeability,

• histamine release,

• release of tissue proteases leading to

autocatabolism, and

• development of oxygen free radicals.

Fibronectin. Fibronectin is an endogenous compound that functions like an opsonin (ie, it enhances phagocytosis). In concert with the reticuloendothelial system, fibronectin helps to clear

particulate matter from the circulation. Many studies have shown that depletion of fibronectin occurs

in a state of multiple trauma, shock, or sepsis.

Fibronectin, in the form of cryoprecipitate, has been

administered to patients who then demonstrate a

slight improvement in their hemodynamic status.

Because cryoprecipitate is a multidonor product,

carrying with it a significant risk for the transmission of infectious agents, great skepticism surrounds

the advisability of using it in the treatment of SIRS/

MODS.

Platelet Activating Factor. Platelet activating

factor can be released from leukocytes, macrophages, or the vascular endothelium. The two effects of this agent are (1) the induction of platelet

and neutrophil aggregation and (2) stimulation of

the arachidonic acid pathway, causing the release

of eicosanoid compounds.

Stress Hormones. Several hormones are released

during a state of physical stress, which characterizes the “fight or flight” survival response. These

include glucagon, hydrocortisone, epinephrine,

growth hormone, and thyroid hormone. One hypothesis concerning this neuroendocrine secretion

is that vascular or organ damage may occur when

states of hypermetabolism and negative nitrogen

balance are created.

Cascade of Events Leading to SIRS/MODS

For SIRS to become fully developed, multiple

endogenous mediators and several different types

of cells interact in ways that result in a continuous

amplification of the original stimulus provided by
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

611

Fig. 24-7. Schematic showing the putative interaction of several endogenous mediators (interleukin-1 [IL-1] and tumor

necrosis factor [TNF]) and the vascular endothelium. The mediators cause the endothelium to generate the potent

vasodilators nitric oxide (NO) and prostaglandin E (PGE), as well as platelet activating factors (PAF). The mediators

also cause a substance (endothelial adhesion molecule) to be formed that attracts circulating neutrophils. The

neutrophils become activated and generate oxygen-derived free radicals and other substances that damage the

microcirculation and contiguious cells. Reprinted with permission from Dinarello CA, Gefland JA, Wolff, SM.

Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. JAMA. 1993;269(14):1830.

endotoxin. This cascade of events (Figure 24-7)

appears to follow this sequence69:

• TNF and IL-1 stimulate endothelial cells to

produce nitric oxide, prostaglandin E2, IL8, and the platelet activating factor.

• Nitric oxide and prostaglandin E2 produce

vasodilation and hypotension.

• IL-8 and the platelet activating factor cause

neutrophils to adhere to the endothelial cells

and then to migrate to the extravascular space.

• Cells are damaged by the release of oxygen-derived free radical from the extravascular neutrophils. If the cellular damage is

sufficiently extensive, organ dysfunction

will occur.

ORGAN-SPECIFIC RESPONSES

If the effects of this cascade are confined to the

local area of microorganism growth and tissue invasion, it is probably advantageous to the patient.

However, if the endogenous mediators and their

effects become systemic, as may occur in human

bacteremia and sepsis/SIRS, then functional impairment of one or more organs can be expected, a

process that may culminate in a perpetuating organ

injury.

Cardiovascular Response

Cardiovascular and hemodynamic dysfunction

in septic shock have been the subjects of much

interest and debate since the 1950s. Two subsets of

patients were initially described in the setting of

Gram-negative bacteremia. The differentiating factor was postulated to be their cardiac index (the

amount of blood ejected by the heart in a unit of

time, divided by the body surface area, and usually

expressed in liters per minute per square meter).

Patients presumed to have a low cardiac index had

cold, clammy skin with weak and thready pulses,

while warm, dry skin and bounding pulses were

attributed to a high cardiac index.70 In 1956, an

animal model of intravenously administered endotoxin elicited a syndrome similar to that ascribed

to low cardiac index (hypotension with a depressed

IL-1 TNF

PAF PGE NO IL-8

IL-1

TNF

Vascular Smooth Muscle

Endothelial Cell Expressing

Adhesion Molecules

Neutrophil

PAF: Platelet Activating Factor Endothelial Cell

PGE: Prostaglandin E

NO: Nitric Oxide

Extravascular Space
Anesthesia and Perioperative Care of the Combat Casualty

612

cardiac index). Most early studies with animals and

humans reported a characteristic hemodynamic

profile of septic shock, particularly in those cases

with a poor prognosis: one of depressed cardiac

output with associated increased systemic vascular

resistance.71

By the mid-1960s, however, the usual hemodynamic pattern seen in septic shock in humans was

reported to be one of normal or increased cardiac

index with an associated low systemic vascular

resistance.72 Subsequent studies have confirmed

that this pattern is the usual cardiac profile seen

early in patients in septic shock.

In retrospect, the occurrence of these two hemodynamic patterns is probably iatrogenic; specifically, the therapy affected ventricular preload.

Therapy during the early 1960s was likely to be

associated with an inadequate restoration of ventricular preload, which therefore led to an inadequate cardiac index. It was thought then that fluid

therapy in septic shock had to be judicious, for

vigorous fluid resuscitation resulted in pulmonary

edema. In reality, much of the lung fluid may have

been related to ARDS, a phenomenon of increased

pulmonary capillary leakage that is most often a

consequence of sepsis. With greater understanding

of ARDS and with the introduction of the pulmonary artery catheter (also called the Swan-Ganz

catheter), patients with depressed cardiac indices

were found to have low left ventricular preload, as

estimated by pulmonary capillary wedge pressure

(PCWP). Thus, in attempting to prevent the development of pulmonary edema, too little volume or

preload was utilized, thereby depressing the cardiac index.73,74 With the PCWP as a guide to left

ventricular preload, infusion of large amounts of

fluids to compensate for the septic shock–induced

vasodilation and capillary leakage results in a pattern of elevated cardiac index in more than 90% of

patients in septic shock.73

Hemodynamic Data Derived From Clinical

Investigation

Despite the hemodynamic pattern described

above, patients who die in septic shock were thought

by many to manifest a falling cardiac index and

progressive acidosis before they die.71 Although

this mechanism of death appears plausible, whether

systemic hypoperfusion was the cause or the effect

remained to be proven.73

To more thoroughly investigate serial cardiovascular variables, 48 consecutive patients with hypotension and blood cultures positive for bacteria

were evaluated.75 With a pulmonary artery catheter

in place, hypotension was managed with fluids,

then dopamine, and finally levarterenol (norepinephrine) as needed to maintain a mean arterial

pressure of at least 60 mm Hg. Hemodynamic

variables were recorded for any change within the

first 24 hours, and at least daily until the patient

either recovered or died. Of the 60% of patients who

died, three fourths had irreversible hypotension.

Eighty percent of this hypotensive group died with

a persistently elevated cardiac index and decreased

systemic vascular resistance. The remaining patients died of continued worsening cardiac index

and heart failure. All these hypotensive patients

died within 7 days of the onset of shock. The

remaining patient (who died after the 7th d), died as

a consequence of MODS. Thus, death from refractory hypotension due primarily to a low cardiac

index is not common. The more likely cause of early

death in patients with sepsis is refractory hypotension associated with a low systemic vascular

resistance.

Early studies that predicted the outcome of patients in septic shock were conflicting, with some

showing a progressive fall in cardiac index and

worsening of a metabolic acidosis prior to death,

others showing no difference from the initial

hemodynamic profile between survivors and

nonsurvivors. One study71 showed that patients

with an extreme elevation in cardiac index (> 7.0 L/

min/m2) had a very poor prognosis. Another75

revealed that an initial heart rate less than 106 beats

per minute, and a rate at 24 hours of less than 95

beats per minute predicted survival. An initial

hyperdynamic response was found in both survivors and nonsurvivors, although survivors tended

to return toward a more normal hemodynamic state

over the first 24 hours, with a decrease in heart rate

of at least 18 beats per minute or a decrease in

cardiac index of at least 0.5 L/min/m2. Nonsurvivors tended to have a persistently low systemic

vascular resistance and an elevated cardiac index

and heart rate.75 Persistent vasodilation may be the

result of systemic absorption of previously mentioned mediators.

Myocardial Dysfunction

Early studies of myocardial dysfunction correlated a low cardiac index, particularly in the setting

of an elevated central venous pressure, with myocardial depression. More sophisticated monitoring

has added other means of evaluating ventricular

function (ie, left ventricular stroke work index
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

613

[LVSWI] in response to volume infusion). Further

calculation of oxygen delivery and consumption

data has been proposed by some as a more accurate

reflection of the adequacy of cardiac function.71

Radionuclide cineangiography was first introduced in the evaluation of patients with sepsis in

1981.76 This technique was used in patients with

septic shock and was reported in 1984.77 Of the 20

patients evaluated, 13 survived. Survivors and

nonsurvivors alike were found to have the characteristic hemodynamic profile seen in septic shock:

an elevated cardiac index with a decreased systemic

vascular resistance. The left ventricular end diastolic volume index (LVEDVI) was also evaluated

(stroke volume index determined from thermodilution cardiac index divided by the radionuclidedetermined ejection fraction); this is a more accurate indicator of left ventricular preload than is

PCWP, because the real determinant of left ventricular ejection is volume (myocyte stretch) not intraventricular pressure. Survivors were noted initially to have a depressed ejection fraction, which

returned to normal in 7 to 10 days. This reduced

ejection fraction was associated with an increased

end diastolic volume index, which also returned to

normal in 7 to 10 days. Thus, in survivors, the initial

decrease in ejection fraction was associated with

left ventricular dilation. This pattern of depressed

ejection fraction with increased LVEDVI has been

subsequently confirmed in other studies using twodimensional echocardiography.73 Thus, the increased cardiac index that occurs despite myocardial depression is the result of both an increased

heart rate and a normal or slightly elevated stroke

volume. Gross dilation of the left ventricle, which

is usually considered to be a pathological process,

can be considered to be a compensatory mechanism

in septic shock, for it allows the maintenance of a

more normal stroke volume and, hence, cardiac

output. Interestingly, nonsurvivors maintained a

normal ejection fraction and left ventricular end

diastolic indices because the left ventricle ejects

against the pathologically low afterload of a dilated

systemic vascular bed.

An increased cardiac index in sepsis requires

adequate preload. In 1977, researchers demonstrated that compared with survivors of septic shock,

nonsurvivors of septic shock had significantly depressed ventricular performance curves. That is,

LVSWI in nonsurvivors was depressed in response

to volume infusion as monitored by the PCWP.78

More recently, ventricular performance curves using LVEDVI, rather than PCWP, as a measure of

preload were studied in three groups of patients—

controls, hemodynamically stable patients with

sepsis, and patients in septic shock.79 In response to

volume infusion, both groups of patients with sepsis

had decreased LVSWIs compared with controls,

and demonstrated no further increase in ventricular

performance when the PCWP exceeded 18 mm Hg.

Volume administration with PCWP as a guideline

may not achieve the expected improvement in left

ventricular performance because left ventricular

end diastolic pressure (LVEDP) is not related to

LVEDVI by a simple linear relation.

Left ventricular diastolic dysfunction also appears in sepsis. Compared with normal controls,

patients with sepsis, both with and without shock,

were shown to have abnormal diastolic filling (Figure 24-8).80 Echocardiographic and pulsed-wave

Doppler studies were characterized by an increase

in peak atrial velocity, increased atrial filling fraction, and prolongation of the atrial filling period as

a function of the diastolic filling period. Septic

patients may have an increased dependence on

atrial systole for diastolic filling.

Right ventricular dysfunction also occurs in patients with sepsis and appears to be independent of

right ventricular afterload. In a study of right

ventricular function in 25 patients in septic shock,

utilizing radionuclide ventriculography as well as

catheterization of the right side of the heart, 13 had

a depressed right ventricular ejection fraction.81 As

expected, right ventricular dysfunction occurred in

patients with respiratory failure or increased pul- Left Ventricular Diastolic Volume

Left Ventricular Diastolic Pressure

Fig. 24-8. This schematic drawing shows the relation

between left ventricular diastolic pressure and volume

for two different states of left ventricular compliance.

The upper curve represents normal diastolic relaxation,

while the lower curve represents impaired diastolic relaxation. Note that for any given filling pressure, the

ventricle with impaired relaxation has a smaller filling

volume. The arrow shows the direction of increasing

impaired relaxation.

Impaired Diastolic

Relaxation
Anesthesia and Perioperative Care of the Combat Casualty

614

cells, and recorded the extent and velocity of shortening. The cells were bathed in sera from 20 patients with septic shock. The sera were then assayed

for evidence of a depressant factor. In a comparison

study71 with sera from three different groups of

patients, sera from the patients in the acute phase of

septic shock caused the least myocardial cell shortening. Of note, there was a significant correlation

between this decrement in vitro and the measured

left ventricular ejection fraction in vivo. This temporal and quantitative association between the in

vitro results and the clinical myocardial depression

noted in vivo appears to validate the presence of a

circulating myocardial depressant factor in patients

with septic shock.71 Revisions in this assay and

subsequent studies have confirmed the association

between myocardial depression in these patients

and a circulating substance that decreases myocardial contraction in vitro.84

A plethora of septic shock mediators has been

evaluated for myocardial depressant activity, of

which TNF and endotoxin have been found to be

the most potent.35,48 Other mediators that may contribute, determined from both animal models and

humans, include prostaglandins, histamine, IL-1

and IL-2, and platelet activating factor. No one

substance appears to be the universal myocardial

depressant substance. Rather, myocardial depression probably occurs as a consequence of many

mediators that may work synergistically.71

Regardless of the actual etiology, survival of

septic shock appears improved when the patient’s

left ventricle dilates sufficient to maintain cardiac

output in the presence of decreased contractility,

due to the circulating myocardial depressant substance. Presumably, the ventricles of nonsurvivors

could not dilate sufficiently to compensate for the

decrease in contractility caused by the circulating

myocardial depressant substance.

Pulmonary Response

The best known clinical manifestations of sepsis/

SIRS are arterial hypoxemia and respiratory failure.

As the lung is probably the first organ to manifest

physiological derangement from sepsis, the astute

clinician will be alerted early to the onset of sepsis,

ideally before shock occurs. Why should the lung be

injured so frequently during sepsis? The following

statements are among the possible explanations86:

• The lung is a source of marginated polymorphonuclear leukocytes.

monary arterial pressures. However, in many of

the patients, the degree of dysfunction was out of

proportion to right ventricular afterload. While 8 of

the 13 patients had concomitant decreases in left

ventricular performance, the ejection fraction was

normal in 5 patients.

In one study,82 significant right ventricular systolic dysfunction, as defined by decreased ejection

fraction and right ventricular dilation, was seen in

all patients in septic shock. Nonsurvivors appeared

to have depressed right ventricular performance

because of a decrease in contractility, as manifested

by a marked increase in end-systolic volume without significant change in right ventricular afterload.

Apparent diastolic dysfunction of the right ventricle was also suggested by the downward displacement of the pressure–volume curves.

Depressed biventricular function and biventricular dilation was noted in another study83 of 38

patients in septic shock; these abnormalities returned to normal within 7 to 14 days. In this study,

31 patients (82%) with depressed right ventricular

function had simultaneous left ventricular dysfunction. Thus, the myocardial depression seen in septic shock is a biventricular phenomenon.71

The mechanism of myocardial dysfunction has

been attributed to either ischemia secondary to inadequate coronary perfusion or the presence of a

circulating humoral factor that depresses myocardial contractility.84 Studies that evaluate coronary

sinus blood flow and myocardial metabolism have

demonstrated neither decreased coronary blood

flow nor increased myocardial lactate production.

High coronary sinus oxygen saturation with a low

myocardial oxygen extraction is similar to the arteriovenous shunting seen peripherally in septic

shock. Thus, septic shock does not appear to cause

myocardial dysfunction by decreasing cardiac perfusion.71

Myocardial Depressant Factor

A circulating humoral substance that results in

myocardial depression has been proposed for many

years. This myocardial depressant factor has been

reported in animal models and in a number of

bioassays that utilize plasma or serum from patients in septic shock. In 1985, using a bioassay of

beating newborn rat heart-cell cultures, researchers85 described a circulating myocardial depressant

substance or factor in patients with septic shock. To

accomplish this, the researchers imaged and analyzed the leading edge of the beating rat myocardial
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

615

• All of the body’s venous return passes

through the lung.

• The lung is exposed to blood-borne mediators and endotoxin.

Clinical Features

The association between lung injury and sepsis is

perhaps best typified by ARDS, a frequently fatal

pulmonary condition. This association has been

known since 1967, when this constellation of clinical signs resulting from a variety of pulmonary

insults was first described.87 In the proper clinical

setting, the presence of ARDS can be inferred from

tachypnea and dyspnea, a decrease in pulmonary

compliance, and refractory hypoxemia and diffuse

alveolar radiological densities. The full-blown syndrome does not always develop; lesser degrees of

impairment of pulmonary function can occur. Hypoxemia during sepsis is frequent and occurs prior

to the onset of pulmonary edema or other changes

characteristic of ARDS. Minimally, most patients

will manifest both an increased intrapulmonary

shunt, resulting in mild-to-moderate hypoxemia,

and an increased physiological deadspace, resulting in an elevated minute ventilation.

Pathophysiology

Most of the data presented here are the results of

experiments on animals. Studies on humans are

difficult or impossible to conduct for the following

reasons:

• Pulmonary dysfunction in patients is frequently not recognized early.

• There are no laboratory markers to chart

the course of impending pulmonary injury

during sepsis.

• When ARDS does develop, it frequently

occurs quickly following the onset of sepsis.

• Histological examination of the lung in the

early phases of sepsis is only possible in the

animal model.

Although the exact incidence of pulmonary dysfunction during sepsis in humans is unknown, the

incidence is probably higher than was reported

previously.86 As is true for other conditions in the

critically ill patient, the reported incidence depends

on the diagnostic criteria. This is particularly important because the terms “sepsis,” “sepsis syndrome,” “septic shock,” and “hypermetabolism”

have been used imprecisely and have been confusing to many clinicians.

The clinical situation of sepsis-induced pulmonary dysfunction is complex and is not due simply

to the presence of a single endogenous mediator or

an inflammatory response. Many factors may contribute to the development of hypoxemia during

sepsis (Exhibit 24-3).

Perhaps the earliest demonstration of pulmonary dysfunction in the septic animal model is an

increase in airway resistance.88 Decreased dynamic

compliance occurs within hours and precedes both

radiographic and clinical evidence of pulmonary parenchymal disease. Increases in airway reactivity

have been demonstrated in humans even during the

recovery phase of ARDS. Bronchoconstriction is likely

the result of release, either locally or systemically, of

endogenous mediator substances in response to endotoxin (in the Gram-negative sepsis models).

Prominent among these mediators are the

byproducts of arachidonic acid metabolism, including the well-described vasoconstrictor thromboxane A2 and the leukotrienes. Other mediators include complement and the proteolytic enzymes and

superoxide radicals generated locally by pulmonary neutrophilic sequestration. This leukocytic

sequestration occurs within minutes of an endotoxin infusion.88 Supporting evidence for the role of

these compounds in the development of increased

airway reactivity is (a) the presence of eicosanoids

in lung lymph flow and (b) the partial attenuation of

abnormal mechanics when prostaglandin antagonists, or nonsteroidal antiinflammatory drugs are

administered. The polymorphonuclear leukocyte

is not, however, an absolute prerequisite for the

development of ARDS; this syndrome has also been

described in neutropenic oncology patients.89

In animal models, pulmonary hypertension also

occurs early after endotoxin infusion.88 Clinical experience in patients with existing pulmonary artery

catheters at the time sepsis develops supports the

frequency with which this physiological alteration

also occurs in humans. Once again, the most likely

etiology for pulmonary vasoconstriction is the

arachidonic acid metabolites. Increased amounts of

thromboxane has been recovered from animals’

pulmonary lymph flow following endotoxin administration. The origin of the release of thromboxane is unclear as the depletion of both neutrophils

and platelets does not prevent the onset of pulmonary hypertension.

An increase in the pulmonary capillary permeability is probably the most widely recognized pul-
Anesthesia and Perioperative Care of the Combat Casualty

616

EXHIBIT 24-3

CAUSES OF HYPOXEMIA DURING SEPSIS

Endogenous mediator-induced bronchoconstriction1

Ventilation–perfusion mismatch due to maldistribution of ventilation, exacerbated by positive-pressure

ventilation2

Increased shunting due to loss of regional hypoxic pulmonary vasoconstriction3

Increased pulmonary vascular permeability leading to interstitial and alveolar pulmonary edema3

Pulmonary hypertension and increased cardiac output leading to an increased gas exchange surface area in

the presence of poor ventilation3

Increased oxygen consumption, both systemically and in respiratory muscles4

Respiratory muscle fatigue5

Alveolar collapse due to decreased surfactant6,7

Sources: (1) Esbenshade AM, Newman JH, Lams PM. Respiratory failure after endotoxin infusion in sleep: Lung mechanics

and lung fluid balance. J Appl Physiol. 1982;54:967–976. (2) Norwood S. Physiologic principles of conventional mechanical

ventilation. In: Kirby RK, Banner MJ, Downs JB, eds. Clinical Applications of Ventilatory Support. New York, NY: Churchill

Livingston; 1990: 145–171. (3) Brighman KL. Specific organ function/dysfunction in sepsis: Pulmonary. In: Sibbald WJ, Spung

CL, eds. Perspective and Sepsis and Septic Shock. Fullerton, Calif: The Society of Critical Care Medicine; 1986: 147–156. (4) Griffel

MI, Asiz ME, Rackow EC, Weil MH. Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during

early septic shock in rats. Crit Care Med. 1990;18(1):72–76. (5) Hussain SN. Respiratory muscle fatigue: A cause of ventilatory

failure in septic shock. J Appl Physiol. 1985;58:2031–2033. (6) Pison V, Obertacke U, Brand M, et al. Altered pulmonary

surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure. J Trauma. 1990;30(1):19–26. (7)

Oldham KT, Guice KS, Stetson PS, Wolfe RR. Bacteremia-induced suppression of alveolar surfactant production. J Surg Res.

1989;47(5):397–402.

monary injury that occurs during sepsis. Lymphflow analysis that demonstrates increases in both

volume and protein content supports the existence

of increased capillary permeability in many septic

animal models. The pathophysiology of this capillary “leak” appears to be largely the result of leukocytic-directed injury to the endothelial lining (ie,

production of superoxide radicals and elastase);

perhaps endothelial gaps are a direct cytotoxic effect of endotoxin.

Although pulmonary edema clearly may worsen

gas exchange, this is not the only cause of hypoxia

during sepsis. Both animal and human measurements have shown a lack of correlation between

calculated variables of the efficiency of oxygenation, (eg, the alveolar-to-arterial oxygen difference, ADO2 – aDO2) and the amount of extravascular

lung water.88 Despite the development of pulmonary hypertension, experimental evidence shows

that within hours of an endotoxin infusion the regional ability of the lung for hypoxic vasoconstriction is lost.86 Thus, blood flow continues to areas of

the lung that are poorly ventilated; the result is poor

gas exchange and hypoxemia.

Renal Dysfunction

The incidence and significance of acute renal

failure in hospitalized patients were documented in

1983, when 2,216 consecutive hospital admissions

were analyzed, revealing 129 episodes, in 109 patients (4.9%) of newly developed renal insufficiency.90 (Impairment in renal function was defined

as an increase of the serum creatinine of 0.5 mg/dL

when the admission serum creatinine was less than

1.9 mg/dL, or an increase of 1.0 mg/dL for patients

with a baseline serum creatinine of 2.0 to 4.9 mg/

dL). This study concluded that decreased renal

perfusion caused new-onset renal insufficiency in

54 episodes (42%), and 10 episodes (19%) were

associated with septic shock. An important finding

was the marked increase in patient mortality, 16 of

25 (64%) when the increase in serum creatinine

exceeded 3.0 mg/dL, compared with 6 of 104 (6.5%)

mortality when the rise in serum creatinine was less

than 3.0 mg/dL.

Consecutive admissions to medical and surgical

ICUs in 13 different medical institutions were evaluated in 1985.91 Definitions for clinically significant
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

617

renal failure were drafted and validated by the

observed rate for survival. In this study, renal

failure was identified by the occurrence of any of

the following measures:

• urinary output < 480 mL/24 h or

<160 mL/8 h,

• serum creatinine > 3.5 mg/dL, or

• serum blood urea nitrogen (BUN) >100 mg/dL.

Another study92 (N = 315) used a stricter definition: a

rise in serum creatinine of 20% above the hospital

admission level. Twenty-nine of 47 (62%) patients

who developed acute renal insufficiency died.

Two studies93,94 addressed the significance of renal failure occurring during sepsis. The first, published in 1980, studied 612 patients with Gramnegative bacteremia and found that the development

of azotemia increased the fatality rate and the subsequent incidence of shock.93 The second, published in 1987, studied 250 consecutive cases of

severe, acute renal failure (defined as a serum creatinine > 5.5 mg/dL) that occurred at a single hospital.94 Of the new cases, 125 (50%) occurred in

medical patients, and 118 (47%) in surgical patients.

Within the surgical group, major vascular surgery

was the most common association (42 of 118). Renal

failure associated with sepsis resulted in a greater

need for dialysis (23 of 24), compared with renal

failure following vascular surgery (33 of 42). Recovery of renal function occurred more frequently

following vascular surgery (22 of 42), compared

with sepsis (5 of 24). In the group of medical

patients, the most common cause of renal failure

was sepsis (29 of 65 patients), which was also associated with a nearly uniform requirement for dialysis (24 of 29) and a low recovery rate (11 of 29). The

mortality rate for sepsis-induced renal failure was

significantly higher than the overall group mortality (62%–78% compared with 44.4%).

Literature revealing the pathophysiological mechanisms of sepsis-induced renal failure is

sparse. Because sepsis and septic shock cause clinical events that may be injurious to the kidney, the

pathophysiology is certain to be multifactorial

(Exhibit 24-4).

EXHIBIT 24-4

PATHOPHYSIOLOGICAL MECHANISMS IN SEPSIS-INDUCED ACUTE RENAL FAILURE

Decreased effective intravascular volume

Decreased cardiac output

Decreased renal blood flow secondary to decreased renal perfusion pressure

Positive pressure ventilation,1

 resulting in decreased cardiac output

Alterations in renal afferent and efferent arterial vasodilation from sympathetic or neurohumoral effects2,3

Tubular obstruction and renal tubular cellular swelling

Concomitant trauma or extremity ischemia resulting in the release of heme pigment

Sepsis-induced disseminated intravascular coagulation

Reperfusion injury (no reflow phenomenon and the release of oxygen free radicals)

Direct effect of substances such as endotoxin4

Nephrotoxic antibiotics used to treat a focus of infection

Intrarenal redistribution of blood flow away from the cortical nephrons5

Sources: (1) Rosenthal MH. Hemodynamic effects of pulmonary insufficiency. Int Anesthesiol Clin. 1986;24:145–148. (2)

Turnquest PE, Rosenthal MH. Acute renal failure in trauma and critically ill patients. Sem Anesth. 1989;8(4)338–346. (3)

Cumming AD, Kline R, Linton AL. Association between renal and sympathetic responses to nonhypotensive systemic sepsis.

Crit Care Med. 1988;16(11):1132–1137. (4) Wardle N. Acute renal failure in the 1980s: The importance of septic shock and of

endotoxemia. Nephron. 1982;30:193. (5) Lucas CE. The renal response to acute injury and sepsis. Surg Clin North Am.

1976;56:953–975.
Anesthesia and Perioperative Care of the Combat Casualty

618

Neurological Manifestations

Dysfunction of the nervous system, particularly

the central nervous system, is of paramount importance, for the degree of recovery determines the

functional status of the patient who leaves the ICU

or hospital. Brain dysfunction may appear early in

sepsis without an infectious agent present in the

central nervous system. Acutely altered mental

status due to sepsis alone has been reported to occur

in approximately 23% of patients with sepsis.95

Clinical Features

Encephalopathy associated with sepsis is usually nonfocal, with mental-status changes ranging

from mild disorientation and confusion through

lethargy, agitation, and confusion, to deep coma.96

Elderly patients appear to be at particularly high

risk; agitation or subtle mental-status changes may

be the only clinical signs of early sepsis in this

group. Metabolic or septic encephalopathy typically presents with a constellation of signs, including normal pupils and eye movements, tremor,

asterixis, and multifocal myoclonus.97 Also, generalized seizures, focal seizures, and other focal signs

such as hemiparesis and gaze paresis have been

seen.98 Thus, the presence of focal findings does not

exclude the clinical presentation of sepsis.

Patients with sepsis may have a multitude of

physiological derangements that may contribute to

encephalopathy. These include not only hypotension, hypoxia, and uremia, but also electrolyte, endocrinological, or metabolic abnormalities. Nevertheless, sepsis-associated central nervous system

depression can occur in the absence of these factors.

Direct microbial invasion or their products such as

endotoxin have been implicated, and diffuse

microabscesses appear to be common in patients

with sepsis.97,98 Patients in septic shock may develop vascular lesions that include cerebral purpura

or microinfarctions.98 Decreases in cerebral blood

flow in these patients may not correlate with mean

arterial blood pressure or perfusion pressure.99

Lastly, administered therapies can also cause

encephalopathy. Common causes include sedative

medications and hyperosmolality or other metabolic derangements from total parenteral nutrition.

Diagnosis and Prognosis

Diagnosis of septic encephalopathy is based initially on diagnosing a central nervous system infection. Computerized tomography scan will show a

mass lesion such as an abscess, hemorrhage, or

infarction, but not cerebral microabscesses, hemorrhages, or microinfarctions. Further resolution may

be sought with magnetic resonance imaging. Cerebrospinal fluid examination is also necessary to rule

out meningitis. Clearly, etiologies for encephalopathies other than meningitis must be entertained,

for the majority of patients with sepsis do not have

a central nervous system infection.96

Although many electroencephalogram changes

occur in septic encephalopathy, they are not specific and may be seen in many toxic and metabolic

encephalopathies. Electroencephalogram changes

include diffuse slow-wave abnormalities, generalized suppression, burst suppression, triphasic

waves, and focal or generalized seizures.97

Prognosis varies with the course of sepsis, failures of other organ systems, associated central nervous system trauma, and the initial Glasgow coma

score. Of patients with nontraumatic coma, 68% of

those whose coma was caused by metabolic disease or

sepsis were either dead or comatose when reevaluated at 2 weeks.100 Patients with acutely altered

mental status due to sepsis have a higher mortality

than those who have no mental-status changes.95

Peripheral Neuropathy

Peripheral nerve dysfunction also appears in

patients with sepsis. This critical-illness polyneuropathy occurs in at least 50% of patients who

remain septic or critically ill for longer than 2 weeks.97

In a study101 of patients with sepsis/SIRS who were

admitted to an ICU for longer than 5 days, electrophysiological studies revealed that 70% developed

some form of polyneuropathy; 30% developed primary axonal degeneration of both motor and sensory fibers. This disorder may present as difficulty

in weaning from the ventilator, with severely ill

patients showing no diaphragmatic responses to

phrenic nerve stimulation.97 Limb weakness and

depressed or absent deep-tendon reflexes occur in

mild cases. In severe cases, the absence of any

voluntary or reflex-induced movement in all four

limbs has been reported.101

This polyneuropathy occurred primarily in older

patients (mean age 64 y) and affected males and

females equally.101 The etiology of this polyneuropathy remains unclear. The factors that most closely

correlated with the development of polyneuropathy

were

• the number of invasive procedures performed,
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

619

• elevated glucose,

• low serum albumin, and

• the duration of stay in the ICU (mean onset

was 28 d).

All patients had concomitant evidence of septic

encephalopathy. Complete recovery occurred only

in patients whose illness was mild to moderately

severe. Patients with a severe peripheral nerve

dysfunction, in which diaphragmatic and limb paralysis occurred, failed to improve and eventually

died. Thus, critical-illness polyneuropathy can have

a significant impact on the course or the eventual

recovery of the patient with sepsis.

Metabolic and Endocrinological Responses

Acute illness or injury results in a hypermetabolic state that is characterized by increased gluconeogenesis, mobilization of fat stores, and rapid

nitrogen metabolism. Oxygen consumption increases and epinephrine, cortisol, and glucagon levels are increased.93 Newly manifested hyperglycemia in a critically ill patient should always raise

the differential diagnosis of early sepsis. The severity of this increased metabolic demand relates in

part to the severity of the illness or injury, with the

resting energy expenditure increasing by 10% to

20% with multiple fractures, 12.9% with respiratory

failure, and 40% to 100% with extensive thermal

injury.102

Immunological Aberrations

Cellular and subcellular interactions, the mediators that are released by these cells, and the response to infection and sepsis were discussed previously in this chapter. The immunological changes

and defects related to trauma, infection, and critical

illness are the focus of this section. Inadequacy or

decrements in immune function predispose the patient to overwhelming sepsis, MODS, and death.

Immunosuppression and Critical Illness

Serious injury or illness primarily affects T cell

function, as reflected by anergy on skin testing. B

cell dysfunction is less common but can appear in

individuals who are ill for a prolonged time period,

are inadequately nourished, or are subjected to

severe burns.43 B cell function is generally assessed

by measuring total serum immunoglobulin levels

or the amounts of the individual immunoglobulin

subclasses. Tetanus toxoid in vivo and pokeweed

mitogen in vitro test the B cell’s recall or secondary

immune function.

Infections. Primary infectious disease processes

often predispose individuals to further infection.

Bacterial pneumonia following viral infection or

bacterial sepsis associated with malaria are common examples. Much of the predisposition may

relate to the breakdown of natural host defenses

from the primary infection. One example is the

tracheobronchial mucous membrane derangements

secondary to the local effects of viral infections.

Infectious diseases that depress cell-mediated immunity can potentially complicate the course of an

already compromised host. Several infections that

have been associated with depressed cell-mediated

immunity in humans include influenza, measles,

infectious mononucleosis, herpes simplex virus,

cytomegalovirus, tuberculosis, histoplasmosis, leprosy, syphilis, pertussis, and streptococcal infections. Malaria has been shown to depress the humoral immune system as well.103 These common

infections, particularly among deployed forces (soldiers are stressed because they have been removed

from their normal immunological milieu), then may

compromise the individual’s immunological response to other insults, such as wound infections or

trauma.

Trauma. Major trauma has a profound effect on

the patient’s immunological function. Total T cell

counts and T cell function are markedly depressed

in response to injury. The T cell count decreases

within hours of injury and may remain depressed

for up to 10 days.1,43 The percentage of T cells in the

peripheral blood remains normal, although it may

decrease to less than 40% of normal 6 to 8 days

following severe burns.1,43,104 The suppressor/helper

T cell ratio increases from 0.55 to 1.04 after trauma.1

Testing of cell-mediated immunity with delayed

cutaneous hypersensitivity testing has found patients to be anergic following major trauma, a condition that usually persists 4 to 7 days.104,105 Persistent anergy is associated with an increase in septic

complications. Up to 59% of trauma victims with

complete anergy to delayed cutaneous hypersensitivity testing develop a significant infectious or

septic process.104,106 Anergy early in a patient’s

course may predict infectious complications, although

later anergy may result from a septic focus.43

B cell counts also fall after trauma, although their

percentage of the total lymphocyte count remains

unchanged.1 Total immunoglobulin levels fall.

Immunoglobulin (Ig) G levels have been shown to

be severely depressed for 1 to 2 months after thermal injury.1,104 However, most of the decrease in the
Anesthesia and Perioperative Care of the Combat Casualty

620

levels of IgG and other immunoglobulins appears

to be dilutional.104

B cell dysfunction does not appear to be a major

factor leading toward increased infection. A study of

burn patients who were immunized with a polyvalent

Pseudomonas vaccine reported effective humoral immune responsiveness; the incidence of Pseudomonas

bacteremia decreased from 16% to 6%.107

Trauma activates the complement pathways, affecting primarily the alternate pathway. The classic

pathway becomes active prior to and during the

appearance of sepsis.1 As a result, serum levels of

complement as well as fibronectin are depressed,

with C3 levels inversely related to the severity of

injury.1,104,108 Fibronectin levels, falling within 4

hours of injury, return to normal within 3 days

barring complications.104

Malnutrition. Most soldiers injured in combat

should be relatively well nourished when injured,

unless they have been involved in an arduous or

protracted campaign. Without adequate nutrition,

immunological dysfunction occurs within days. T

cell numbers decrease and the function of T-helper

cells is impaired. Evaluations of cell-mediated immunity have revealed a relationship between malnutrition, anergy, and humoral immunological impairment. In response to new antigens, these

patients’ immunoglobulin generation is impaired,

leading to an increased infection rate.43,109

Surgery in the Immunocompromised Patient

With Sepsis/SIRS

Wounded casualties frequently require surgery,

and anesthetic agents can contribute to significant perioperative immunological aberrations.

Halothane, nitrous oxide, and pentothal decrease

total lymphocytic counts and the number of antibody-forming cells in the spleen.110 Polymorphonuclear leukocyte chemotaxis and phagocytosis is

also impaired.109

The immunological abnormalities that occur in

accidental trauma also appear in patients who undergo the more controlled traumatic injury performed in the operative suite. For example, the

phagocytic capacity of reticuloendothelial cells is

depressed following surgery and trauma in proportion to the severity of the insult. Opsonization of

bacteria, which enhances these cells’ function, is

depressed, perhaps as a result of decreased levels of

the major opsonic protein, fibronectin.109 Administering cryoprecipitate that contains high levels of

fibronectin to surgical and traumatized patients

with sepsis has been shown to improve physiological variables (cardiac index, oxygen consumption,

oxygen delivery, and pulmonary shunt fraction);

however, improved survival has yet to be shown

definitively.111

Cell-mediated immunity is the immunological

function most affected in the postoperative patient.

T cell changes parallel those described above in the

traumatized patient. In 46 otherwise healthy,

nontraumatized patients who were studied, minor

surgical procedures under general anesthesia did

not appear to alter skin test results significantly (ie,

these patients did not become anergic).112 However,

of patients who underwent major cardiovascular

procedures (such as coronary artery bypass grafting or abdominal aortic aneurysm repair), 42% became anergic by postoperative day 3. Compared

with patients who retained their immunocompetence, these anergic patients had more infectious

complications and were hospitalized longer. Restoration to normal, reactive skin tests may take as

long as 28 days.

Perioperative hemorrhage that requires the transfusion of 10 or more units of blood in 24 hours has

a mortality rate of approximately 50%. Young,

otherwise-healthy trauma victims who require 25

or more units of blood have a 71% mortality rate.104

Transfusion of blood appears to contribute to the

immunological depression seen in trauma victims,

even allowing the prediction of subsequent infection.113 Only 10% of patients who received no transfusion developed an infectious complication,

whereas 80% of patients who required more than

15 units of blood did.

Persistent anergy has been seen in postoperative

patients with sepsis. The prompt return of normal

skin tests follows surgical drainage of an intraperitoneal abscess, an infected common bile duct, or

another inflammatory process.114

Immunological depression in the battlefield casualty may occur in response to many factors. The

severity of these defects clearly dictates the patient’s eventual outcome and survival. As no specific therapy has yet been proven to correct these

immunological defects, meticulous patient care is

important to prevent compounding immunological

depression.43

Hematological and Coagulation Defects

Sepsis adversely affects the hematopoietic system, resulting in a variety of clinical maladies that

can complicate an already seriously ill patient’s

course. Pancytopenia, which may occur in a variety

of medical illnesses, clearly predisposes a patient to
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

621

develop significant infections. On the other hand,

pancytopenia has also been caused by infections

such as Mycobacterium tuberculosis, atypical mycobacteria—especially Mycobacterium kansasii, Histoplasma capsulatum, Salmonella typhi, Mucor species,

and Brucella species.115 Isolated infections (eg,

localized pulmonary infections) do not typically

cause this significant hematological insult. Rather,

overwhelming infection (during which these organisms are frequently recovered on bone marrow

culture) is the typical clinical scenario leading to

pancytopenia.

Leukocyte Interactions

Neutrophilia. The degree of neutrophilia varies

among patients and the severity of their infections.

Mild, localized infections may be associated with

neutrophil cell counts of 12,000 to 14,000/mm3,

while severe, pyogenic infections may have cell

counts reaching 50,000 to 75,000/mm3. Leukemoid

reactions with cell counts of 50,000 to 100,000/mm3

are exaggerated responses to these phenomena and,

although uncommon, they do occur in a substantial

number of infections (eg, pneumonia, meningitis,

diphtheria, and tuberculosis).115

Neutrophil-releasing factor is stimulated by endotoxin and may, in fact, be the activated complement component C3a.96 IL-1 also plays a role in the

release of neutrophils from the bone marrow.115

Neutrophilia that persists with chronic infection is

probably mediated by colony-stimulating factors,

which increase the cell division and turnover of

granulocyte precursors.

Although most bacterial infections result in a

leukocytosis, this is not universal. In a study of

medical patients with sepsis whose blood cultures

were positive for bacteria, only 69% had leukocytosis

on the first day of septicemia.116 Neutrophilia is

uncommonly seen in infections caused by Chlamydia species, Mycoplasma species, Rickettsia, Mycobacteria, and fungal infections.115

Neutropenia. Neutropenia is characteristically

seen in infections such as typhoid fever, brucellosis,

salmonellosis, pertussis, rickettsial infections, disseminated histoplasmosis, and disseminated tuberculosis. However, development of neutropenia in a

patient with sepsis may portend a bad prognosis

and may result from splenic sequestration, altered

immunity, complement-induced neutrophil aggregation,96 or increased neutrophil consumption in

the setting of depleted bone marrow. This condition can be seen in infants, the elderly, and patients

with alcoholism, diabetes, malnutrition, or shock.

Neutrophil Morphology. In a study116 of medical

patients with sepsis, 38% had toxic granulations

noted on the initial day of sepsis and over one half

developed them at some time during their septic

course. Another study117 of patients with bacteremia

and fungemia found toxic granulations in 75%.

Döhle bodies, Pelger-Huët anomaly (bilobed neutrophils), and vacuolation were also found, the latter being touted as a sensitive and specific marker

for bacteremia.96 However, although they are suggestive, none of these findings are pathognomonic

for infection.

Eosinophils. Eosinophilia is rare in bacterial and

fungal infections, though in adults it is common in

bronchopulmonary aspergillosis and coccidioidomycosis.115 It classically occurs in invasive helminth infections. Eosinopenia (50 cells/mm3), on

the other hand, commonly heralds the onset of

severe bacterial infections. Causes include margination or migration of these cells from the vascular

space, inhibition of bone marrow release, and lastly,

a decrease in bone marrow production.96 The absence of eosinopenia when a febrile patient is evaluated is thought by some to question the diagnosis of

severe infection.118 Counts greater than 5% may

suggest a nonbacterial etiology such as drug fever,

Addison’s disease, myeloproliferative disease, or a

parasitic infection.96 Although without defined sensitivity and specificity, eosinopenia is commonly

associated with the acute onset of sepsis.

Monocytes and Lymphocytes. Monocytosis

(> 800 cells/mm3) has been associated with a variety of infections, though usually in those of a subacute or chronic course. It is found in approximately 15% to 20% of patients with disseminated

tuberculosis, and similarly in those with subacute

bacterial endocarditis.115 Because there is no bone

marrow reserve of monocytes, an increased turnover in association with exudates may result in a

monocytopenia.118

Lymphocytosis (> 4,000 cells/mm3) is not usually seen in traumatized patients with sepsis.

Lymphocytosis occurs commonly in pertussis, rarely

with other bacterial or fungal infections, and occasionally in tuberculosis, syphilis, brucellosis, rickettsial, and viral infections. More commonly, however, lymphocytopenia (< 1,000 cells/mm3) is

associated with acute bacterial infections.

The Effect of Sepsis on Erythrocytes

The principal erythrocytic response to infection

is anemia, which can arise after several days in an

acute, severe infection but is more typically associ-
Anesthesia and Perioperative Care of the Combat Casualty

622

ated with chronic bacterial or fungal infections. The

rapid appearance of anemia in an acute infection is

the result of one of four processes118:

1. hemorrhage,

2. erythrocyte destruction secondary to the

infection itself (eg, malaria),

3. microangiopathic hemolysis in association

with disseminated intravascular coagulation (DIC), or

4. activation of an underlying, preexisting

hemolytic process.

Although most patients are anemic when they

are admitted to a medical ICU, 85% demonstrate a

further drop in hematocrit in association with

sepsis.116 A reticulocytopenia as well as a shortened

erythrocyte survival time persist for approximately

2 weeks in these patients. Occasionally, hypochromic and microcytic indices occur when iron metabolism is disturbed, resulting in low values for

serum iron and transferrin. Two possible causative

factors are IL-l and TNF. Of particular significance

is IL-1’s ability to induce the release and activation

of lactoferrin from neutrophils and to decrease hepatic transferrin synthesis, both of which contribute to the decrease in serum iron. Decrease in serum

iron levels may, in part, be a host-defense mechanism, for free iron contributes to microbial virulence. Chronic anemia that develops during the

first month of an illness is typically normochromic

and normocytic. Anemia may result from chronic,

suppurative infections such as meningitis, empyema, cavitary pulmonary disease, endocarditis, or

occult intraabdominal abscesses. Although a variety of bacterial and fungal agents have been reported to cause hemolytic anemia, it actually occurs

only rarely. Although three fourths of patients

infected with Mycoplasma pneumoniae develop cold

agglutinins, Coombs-positive hemolytic anemia is

exceedingly rare.115

Sepsis-Induced Platelet Dyscrasia

Thrombocytopenia (platelet counts < 150,000/

mm3) is present in 33% of medical patients with

sepsis and blood cultures that are positive for bacteria.116 In 65% of these patients, the thrombocytopenia is recognized prior to the onset of sepsis.

Most of these patients experience further declines

in their platelet counts. The incidence of

thrombocytopenia in patients with sepsis ranges

from 30% to 100%.115,119 Approximately two thirds

of patients with bacteremia have platelet counts

lower than 150,000/mm3, while one third have platelet counts lower than 50,000/mm3.

120 Thus,

thrombocytopenia is a common finding in patients

with sepsis, particularly when associated with DIC

(88%–100% incidence).115

Thrombocytopenia may occur in critically ill patients prior to the onset of severe infections. Many

etiologies for depressed platelet counts are present

in this patient population and have been reviewed

elsewhere.119 Briefly, low platelet counts can be due

to clumping and therefore spurious, thus warranting close evaluation of the peripheral blood smear.

Platelet production can be depressed from the use

of alcohol or drugs, toxins, infection-induced

aplastic anemia, and nutritional deficiencies, particularly vitamin B12 or folate. Distribution and

dilution problems also result in thrombocytopenia,

as occurs in hypersplenism, hypothermia, and massive transfusion or fluid therapy.

Another category of causes of thrombocytopenia

is platelet consumption or destruction. This is the

most common reason for thrombocytopenia found

in the critically ill patient, and it occurs via two

mechanisms: nonimmune (mediated by thrombin or

surface interactions) and immune-mediated. Either

mechanism—alone, or in concert with the other—

contributes to thrombocytopenia in many settings,

only one of which is infection. The most common

means of increased platelet destruction during bacterial infections is consumption during DIC. The

organisms most commonly implicated are Neisseria

meningitidis, Escherichia coli, Pseudomonas aeruginosa,

and Klebsiella pneumoniae.

119

Bacterial, viral, fungal, rickettsial, and protozoal

infections all may cause thrombocytopenia. Although usually associated with blood-borne organisms, thrombocytopenia can develop in severe infections with blood cultures that are negative for

bacteria (eg, pneumonia, peritonitis, or abscesses).115

Platelet aggregation, particularly as induced by

Staphylococcus aureus or endotoxemia, is a major

cause of increased platelet turnover. An immunologically mediated destruction is also seen, particularly in Gram-negative infections. Platelet-associated IgG has been found to be elevated in almost

three fourths of patients with Gram-negative sepsis

and thrombocytopenia, and in 80% of patients with

Gram-positive sepsis.121 Damage to vascular endothelial cells by Rickettsia species and perhaps

Neisseria meningitidis may result in increased platelet adherence.119,120

Viral-induced thrombocytopenia is probably as

common as that associated with bacterial infections.119 Viral infections commonly implicated in-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

623

clude mumps, varicella, disseminated herpes simplex, cytomegalovirus, infectious mononucleosis,

rubeola, and rubella.120 Thrombocytopenia is also

common in HIV infections, whether it be based

solely on serologic evidence or in association with

acquired immunodeficiency syndrome (AIDS).120

Although usually mild, the thrombocytopenia seen

in these infections can at times be life threatening.119

Finally, protozoal infections that can be seen in

deploying forces can cause thrombocytopenia. A

chronic disorder is seen with toxoplasmosis, whereas more-acute thrombocytopenia, often in conjunction with DIC, is seen in malaria or trypanosomiasis.120

Disseminated Intravascular Coagulation

The development of DIC in patients with sepsis,

particularly sepsis from Gram-negative organisms,

has been well described.118,122 Endothelial cells become damaged, activated, or are shed as a consequence of the onset of sepsis. Contributory factors

include endotoxin, cellular hormones such as TNF,

and tissue hypoxia. Tissue thromboplastin is released and, with exposed collagen, causes platelet

adhesion and activation. Diffuse coagulation ensues and overwhelms normal compensatory mechanisms. Fibrinogen, platelets, and coagulation factors are consumed. The formation of fibrin and

fibrin monomers activate the fibrinolytic system,

which then produces fibrin degradation products.

These products then inhibit coagulation, impair

platelet function, and can cause pulmonary vascular constriction.118 The predominant clinical findings in DIC, whether they may be thrombosis or

hemorrhage, depend upon the balance of pathological processes or the competing compensatory

mechanisms.

Dermatological and Ophthalmological

Manifestations

Outward cutaneous manifestations of sepsis are

often present and may be overlooked in the evaluation of the patient with sepsis. Three patterns of

cutaneous lesions appear in these patients.96 The

first is a consequence of bacterial invasion directly

into the skin or subcutaneous tissues. Both the

nature of the invading organism and the host’s

response determine the appearance of the lesion.

The second occurs as a result of the septic picture,

such as hypotension or DIC, without direct cutaneous involvement of the infection. And third, signs

of immune-mediated vasculitis or microinfarctions

from infective endocarditis may appear.

Gram-negative sepsis from Campylobacter fetus,

Vibrio species, Aeromonas hydrophila, Bacteroides species, Yersinia enterocolitica, and Serratia marcescens

cause cellulitis, erysipelas, and fasciitis.96 The lower

extremities are at particular risk, with C fetus causing lesions that may appear similar to deep venous

thrombosis.123

Bacterial involvement of the skin and subcutaneous tissues can occur without much associated inflammation and can therefore appear in the

granulocytopenic host. The invading organisms

are usually Gram negative, particularly Pseudomonas aeruginosa, and initially form vesicles or erythema

multiforme. These later progress to necrotizing

bullous lesions, termed ecthyma gangrenosum.124

In sepsis, DIC is associated with acrocyanosis of

peripheral tissues such as the fingertips, toes, ears,

and nose.96 Subsequent necrosis may occur and is

termed symmetrical peripheral gangrene. Although

typically associated with Gram-negative infections,

these findings can also occur in sepsis associated

with Gram-positive organisms.

In patients who have ophthalmological complications of sepsis/SIRS, fundoscopic examination

can often aid in the diagnosis of the causative organism. Common, nonspecific retinal changes include retinal hemorrhages, cotton wool spots, and

subconjunctival hemorrhages. Roth’s spots secondary to infective endocarditis can also appear.

Other nonbacterial organisms can present with retinal findings. These include viruses such as cytomegalovirus, parasites such as toxoplasmosis, and fungi

such as Candida species.71 Ophthalmological consultation for diagnosis and management is usually

necessary for many of these disorders.

DIAGNOSIS AND MONITORING

The physician’s senses of vision, hearing, and

touch, accompanied by a high index of suspicion,

remain the most valuable monitors for the early

detection of sepsis. No other diagnostic tool can

replace the clinical acumen of an experienced physician. However, regardless of the physician’s clinical experience, various laboratory analyses should

be made to confirm the diagnosis. The microbiologic diagnosis of the potential cause of sepsis in a

patient requires proper submission and handling of

the specimens. Close coordination between the clinician and the microbiology laboratory is indicated.
Anesthesia and Perioperative Care of the Combat Casualty

624

Hematological Evaluation

The clinical and laboratory diagnosis of sepsis

and septic shock were reviewed earlier in this chapter. Typical findings include: leukocytosis with a

left shift or leukopenia, thrombocytopenia, and prolonged prothrombin time or activated partial thromboplastin time.125 Most hematological and chemistry studies are routinely performed on critically ill

patients, based on a thorough history and physical

examination. The patient’s clinical condition and

course should then dictate the diagnostic laboratory studies to be performed.

Microbiologic Evaluation

Diagnosis of the infection responsible for the

septic picture in the critically ill patient requires

that adequate, appropriate, and representative

samples be collected for laboratory and microbiologic processing. Specimens of blood and respiratory-tract exudates are the most frequent submissions for evaluation. Urine samples obtained from

clean-catch, mid-stream, catheter, or suprapubic

specimens are also usually submitted for evaluation. Significant values are more than 106 organisms per milliliter, although any growth in newly

catheterized or suprapubic specimens is significant. Other specimens from body fluids, exudates,

pus, and mucous membranes also require submission for study.

Ideally, specimens should be collected from normally sterile body sites and not be contaminated by

the usual skin or mucous-membrane flora. Whenever possible, tissue specimens are preferred over

specimens obtained via swabs. Specimens also

require prompt transport to the laboratory for proper

processing to ensure optimal recovery of the causative organisms. If possible, the specimens should

be obtained before antimicrobial therapy is initiated.125

Specimens should initially be examined directly.

The test that should be performed most commonly

is the Gram’s stain, to evaluate the bacterial population in the specimen. Wet mounts are useful in

demonstrating protozoa; india ink or potassium

hydroxide is added to look for Cryptococcus neoformans or fungi, respectively. Acid-fast stains identify Mycobacteria species and fluorescent stains can

identify Legionella. Silver stains are useful for fungi

and Pneumocystis, and malarial parasites can be

seen with a Giemsa stain.126

Cultures are performed on all suitably submitted

specimens. Different isolation techniques are required for the wide variety of bacteria, fungi, viruses, and protozoa. Once an organism is identified, the susceptibility of the isolated pathogen to

various antimicrobial agents is performed. Susceptibility or resistance to the agent is expressed as the

minimal inhibitory concentration of the antimicrobial agent required to prevent the growth of a specific inoculum of organisms. The therapeutic goal

in choosing an antimicrobial agent is to achieve a

mean drug concentration in the affected tissue that

is 2- to 4-fold greater than the minimal inhibitory

concentration.126

Blood Cultures

Bacteremia, particularly with Gram-negative organisms, is the prototypical infection that causes

sepsis and septic shock. Blood cultures obtained

from sterile venipunctures are the primary means

of detecting bacteremia. In untreated patients who

eventually develop bacteremia, a single blood culture will be positive approximately 75% of the time;

if three blood cultures are drawn, this rate increases

to 98%. Most of these cultures turn positive during

incubation within 72 hours. Thus, three sets of

blood cultures observed for 3 days will detect

Gram-negative bacteremia in more than 90% of

patients who will eventually become bacteremic.127

Respiratory-Tract Cultures

Specimens from the respiratory tract are usually

obtained from sputum samples taken via an endotracheal tube. (Obtaining pulmonary specimens is

complicated by the inevitable contamination by

upper-airway flora. Gram-negative organisms that

colonize the upper airways of patients in the ICU

may or may not be pathogenic.) Examination of the

sputum is necessary to ensure an adequate sample.

In the nonintubated patient, finding a single dominant type of organism in the presence of polymorphonuclear cells is useful in determining the pathogenic organism of a lower-respiratory-tract

infection. The reliability of these criteria is less well

known in intubated patients.126 Potential complications and the lack of clinically useful data have

caused the use of transtracheal aspiration to decline.

Specimens obtained via bronchoscopy may be

useful for microbiologic study of the respiratory

tract. Simple bronchial washings for bacterial flora

are difficult to interpret; the reliability of these

specimens to diagnose lower-tract infections is similar to that of sputum cultures. Protected brush
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

625

specimens may improve the diagnostic yield; the

sensitivity and specificity for properly diagnosing

the etiologic bacteria normally ranges from 59% to

70%, although some report 90%.126

Bronchoalveolar lavage has also proven to be a

beneficial means of obtaining specimens and is particularly efficacious in patients with AIDS. Yields

of nearly 100% for Pneumocystis carinii have been

reported, with yields for other pathogens ranging

from 60% to 85%.126 Bronchoalveolar lavage makes

it possible to diagnose infections by means of both

rapid-staining techniques and cultures. Rapid stains

for Pneumocystis, viral inclusions, Legionella, fungi,

Mycobacteria, and bacteria have been beneficial in

aiding early, appropriate antimicrobial therapy.

Additional Tests

Diagnostic tests other than culturing can be performed to determine the potential cause of sepsis in

a patient. Capsular polysaccharide antigens can be

detected for Hemophilus influenza, Streptococcus

pneumoniae, Neisseria meningitidis, or Cryptococcus

neoformans. Enzyme-linked immunosorbent assays

(ELISAs) to detect bacterial antigens have been useful in diagnosing infections by N gonorrhea and

Legionella species. And lastly, serologic evidence

for antibody detection has been used to diagnose

typhoid fever, brucellosis, tularemia, Legionnaires’

disease, acute viral diseases, histoplasmosis, rickettsial typhus and spotted fevers, toxoplasmosis,

and amebiasis.126 Other organisms are being detected and other diagnostic measures are continually being developed.

Sophisticated Bedside Monitors

Because significant cardiovascular dysfunction

occurs in sepsis/SIRS, accurate assessment of hemodynamic function is imperative to successfully manage these critically ill patients. Clinical assessment

and observation often fail to accurately determine

the hemodynamic status, and, hence, the optimal

therapy for these patients. Hemodynamic monitoring can be invasive and noninvasive.

Pulmonary Artery Catheter

The development of the flow-directed pulmonary artery catheter has enabled us to more accurately assess the hemodynamic status of patients

with sepsis. Newer catheters now allow the physician to measure and calculate intracardiac and pulmonary arterial pressures, cardiac output and cardiac index, intracardiac and mixed venous oxygen

saturation, right ventricular ejection fraction, right

ventricular end diastolic and end systolic volumes,

and “continuous” cardiac output.128 With this information at hand, the clinician can obtain a more

accurate assessment of the patient’s intravascular

volume status and ventricular performance, calculate hemodynamic and respiratory indices to aid

management, and determine oxygen delivery and

tissue oxygen consumption.

Many indications for the use of the pulmonary

artery catheter have evolved since its introduction.129,130 If ARDS develops in the patient with

sepsis, it can be more readily diagnosed and managed with a pulmonary artery catheter that distinguishes cardiogenic from noncardiogenic pulmonary edema. Particularly in the traumatized or

postoperative patient, intravascular volume status

can be more accurately assessed.

Insertion techniques have been described in detail elsewhere.131 Catheterization of the pulmonary

circulation can be performed by inserting the pulmonary artery catheter into the internal jugular,

subclavian, femoral, or antecubital veins. Minor

and major complications can occur with the placement and use of these catheters, however.128,132 Insertion complications include bleeding, vessel perforation, pneumothorax or hemothorax, and ventricular

dysrhythmias. Maintaining the catheter in the pulmonary artery has complications, as well. These

include local vascular thrombosis, pulmonary arterial rupture, pulmonary infarction, or catheter-related sepsis. So, although a pulmonary artery catheter is beneficial in the management of patients

with sepsis, further injury is possible and warrants

consideration before the catheter is inserted.

Two major assumptions must be made before the

data obtained from the pulmonary artery catheter

can be interpreted correctly:

1. The equipment must be properly functioning and calibrated, and the transducer zeroed at the mid-left atrial level. The function of the pulmonary artery catheter is to

obtain an estimate of left ventricular

preload, which is determined by left ventricular end diastolic volume.

2. A direct relationship is assumed between

the left ventricular end diastolic volume,

which is difficult to measure, and the more

easily obtained left ventricular end diastolic pressure. Changes in left ventricular

compliance, however, alter this volumeto-pressure relationship.
Anesthesia and Perioperative Care of the Combat Casualty

626

Under conditions of a normal pulmonary vascular

bed, mitral valve, and left ventricular function or

compliance, PCWP measured at end expiration in

pulmonary zone III is equal to both the mean left

atrial pressure and left ventricular end diastolic

pressure. The second major assumption is altered

by changes in any of these factors or catheter placement.129 Other factors, such as the application of

positive end-expiratory pressure to mechanical ventilation, also alter this assumption.

Pulmonary artery catheters also provide a means

of obtaining an estimate of cardiac output by

thermodilution. Using the proper volume and temperature of injectate required by the specific catheter and cardiac computer is of utmost importance

in obtaining an accurate estimate. Timing the injections for cardiac output measurement within the

same period in the respiratory cycle may improve

the reproducibility of the results. However, indiscriminate timing of injections for cardiac output

throughout the respiratory cycle more accurately

determines the clinical status of the patient. Cardiac output divided by body surface area yields

cardiac index, a figure that can then easily be compared between individuals. Obtaining these figures is necessary to determine systemic vascular

resistance (SVR), pulmonary vascular resistance

(PVR), stroke work index (SWI), and oxygen delivery (DO2).

One measurement that can be obtained only from

a pulmonary artery catheter is a mixed venous

blood gas. This measurement can be (a) obtained

intermittently or, via a specially designed catheter

that uses reflectance oximetry, (b) monitored continuously. The measurement of venous oxygen

saturation (SvO2) is necessary to determine oxygen

consumption (VO2).

SvO2 varies directly with cardiac output, hemoglobin, and arterial oxygen saturation. Decreasing

SvO2 may result from increased metabolic rate, with

concomitant tissue extraction of oxygen or decreased

oxygen delivery as a result of cardiac dysfunction,

anemia, or arterial hypoxemia. Increases in SvO2

occur where less oxygen is either utilized or extracted,

as in arterial-venous fistulae, cirrhosis, left-to-right

cardiac shunts, peripheral shunts, cyanide poisoning,

hypothermia, inadvertent sampling of blood from

the pulmonary artery (taken when the catheter is

improperly inflated or wedged), and sepsis.128

Sepsis causes an increase in measured SvO2 as a

result of decreased tissue oxygen extraction when

1. a disproportionately high percentage of

cardiac output is distributed to the skin,

where oxygen consumption is minimal,

and

2. microvascular occlusion occurs from leukocyte aggregates, microthrombi, vasoconstriction, and platelet aggregates.

Additional findings that typically occur in patients

with sepsis with a pulmonary artery catheter in

place include

3. a moderate-to-high cardiac output in the

presence of

4. a low systemic vascular resistance.

These findings are necessarily contingent on other

determining factors such as adequate hemoglobin,

arterial oxygen saturation, and intravascular volume.

Any reduction in these determining factors could

lead to misinterpretation of the data. Using a pulmonary artery catheter has aided the diagnosis of unsuspected sepsis. One study revealed that unsuspected

septic shock was diagnosed in 38% of patients only

after a pulmonary artery catheter was inserted.133

Whether the use of pulmonary artery catheters improves outcome from septic shock remains to be

definitively determined. Proponents have advocated its use to optimize oxygen delivery to tissues

in an attempt to maintain adequate tissue oxygen

consumption and hence, improve survivability.

Echocardiography

The major noninvasive means of evaluating cardiac performance is the echocardiogram. Through

the use of the traditional M-mode echocardiograph,

two-dimensional echocardiography, and the recently developed Doppler color-flow mapping,

echocardiography can be used to assess left ventricular function both quantitatively and qualitatively, diagnose ischemic heart disease, to include

infarction, evaluate pathological lesions in and

around the heart in the great vessels, and observe

intracardiac blood flow through the valves and

intracardiac shunts.134 The effectiveness of these

studies has been further improved through the development of transesophageal imaging. Placing the

transducer within the chest cavity can eliminate

many of the artifacts of chest-wall deformities, subcutaneous tissue, emphysematous lungs, or even

surgical bandages, and thus provide a more accurate, detailed study.

In addition to these diagnostic capabilities,

echocardiography can now be used as a noninvasive

monitor of cardiac output via a continuous-wave
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

627

Doppler cardiac-output computer. This technique

depends on measuring blood flow velocity through

the aortic valve and accurately measuring the crosssectional area of the valve.134 Two transducers are

used, one in the suprasternal notch and the other on

an esophageal stethoscope. Cardiac output is determined by the formula:

C.O. = SVI • Ao area • HR

where C.O. represents cardiac output, SVI (systolic

velocity integral) represents the integral of the area

under the velocity curve measured by the transducer aimed at the aortic valve, Ao area represents

the cross-sectional area of the aortic valve (usually

measured by M-mode or two-dimensional echocardiography), and HR represents heart rate.

The accuracy of Doppler-measured cardiac output depends on both the patient and the operator.

Comparisons with standard thermodilution techniques have been in conflict, although a correlation

between r = 0.88 and 0.97 has been reported.134

Echocardiography has proven useful in the evaluation of patients with sepsis. Two-dimensional

echocardiography has been used to monitor myocardial failure and ventricular dilation, as well as

the recovery from septic shock.135 Segmental myocardial dysfunction in septic shock can be seen by

echocardiography. Typically associated with

ischemic heart disease, this abnormality has also

been seen in patients with sepsis who have no

evidence of either coronary artery disease or myocardial injury.136

Echocardiography may not at this stage replace

invasive pulmonary arterial catheterization in

the evaluation and management of patients with

sepsis. It is, however, complementary, as it is able

to monitor chamber size in sepsis and during therapeutic interventions.137 Improvements in equipment and the development of other noninvasive

techniques such as bioimpedance cardiography will

further increase our ability to obtain information

about the hemodynamic status of patients with

sepsis.138

Radiological Procedures

Many radiological procedures may be beneficial

in the diagnosis and management of patients with

sepsis. All procedures and tests must be performed

while keeping in mind the potential complications

inherent in preparing and transporting the patient,

and weighing these potential complications against

the potential benefit from obtaining useful information. Suboptimal patient preparation, such as the

inability to administer oral contrast solution prior

to an abdominal computed tomography (CT) scan,

impairs the adequacy of the results and may warrant delaying the study.

Chest Radiography

The principal radiographic study utilized in the

evaluation and management of the critically ill patient with sepsis is a chest roentgenogram made by

a portable X-ray apparatus. The roentgenogram

must be reviewed in a systematic fashion, examining from the peripheral soft tissues to the mediastinum and including all structures, including those

iatrogenically placed.

Evaluation of the pulmonary parenchyma is usually the focus of attention in the patient with sepsis.

In these patients, loss of alveolar space is commonly

in the form of atelectasis (loss of lung volume),

which appears rapidly and occurs commonly in the

postoperative setting.

Pneumonia can present as a wide variety of radiographic appearances. It can be interstitial and

diffuse or localized with dense, airspace consolidation. Combinations and variations are common.

The definitive diagnosis requires information other

than that obtained on the roentgenogram, as

atelectasis or pulmonary edema may be indistinguishable from pneumonia.139

Patients with ARDS usually present with a diffuse interstitial and alveolar infiltrate, which many

diffuse pulmonic processes can mimic. These other

processes include pulmonary edema, fat embolism

syndrome, diffuse pneumonia, or massive aspiration pneumonitis.139 The definitive diagnosis requires further clinical and hemodynamic data and

cannot be made solely on the basis of its radiographic appearance.

Pleural-based disease must also be evaluated.

Pleural fluid is not specific and can occur in a wide

variety of disorders in the septic patient, including

congestive heart failure, empyema or parapneumonic inflammation, and pancreatitis. The pleural

space must also be evaluated for evidence of

barotrauma, as pneumothorax is common in mechanically ventilated patients (with an incidence of

approximately 10%). Pleural air is usually seen

without difficulty in an upright film. However, in

the supine patient, air may collect in the anteromedial portion of the hemithorax, producing a medial pneumothorax, or dissect over the hemidiaphragm, producing an abnormally deep costophrenic sulcus (the deep sulcus sign).139
Anesthesia and Perioperative Care of the Combat Casualty

628

Sinus Evaluation

Critically ill patients frequently require nasotracheal intubation, nasogastric suctioning, or

nasogastric feeding, all of which may cause

iatrogenic sinusitis. Sinusitis should be considered

in the differential diagnosis in the seriously ill,

febrile patient. Physical exam and bedside routine

sinus roentgenograms frequently miss the diagnosis. CT is useful in making the diagnosis of occult

sinusitis-induced sepsis.140

Ultrasonography

Ultrasonography has proven beneficial in the

diagnosis of clinical dilemmas in critically ill patients with sepsis. Improved imaging and portability have made bedside evaluations possible. The

bedside procedure is safer for the patient as well, as

it obviates the need to transport the patient to the

radiology department (which, for critically ill patients, is potentially complicated and dangerous).

Ultrasound can now be used in the initial evaluation of acute renal failure to screen for obstruction,

with a 93% to 98% sensitivity in the detection of

hydronephrosis.141 Intrinsic renal disease and renovascular disease can also be evaluated, the latter

aided by Doppler analysis. Acute pancreatitis, which

can accompany or mimic sepsis, can also be evaluated by ultrasound. Diagnosis of the complications

of pancreatitis, such as hemorrhage, pseudocysts,

or biliary tract obstruction can all be confirmed by

sonography.

Biliary tract evaluation can help determine the

etiology of jaundice that may appear in the septic

patient. By identifying and measuring the common

hepatic duct, obstructive jaundice can be diagnosed

with 90% accuracy.141 Hepatocellular disease is

evaluated with much less sensitivity. Using

ultrasonography to exclude intraabdominal fluid

collection is particularly useful. Those areas most

amenable for study are the right upper quadrant

(liver, subhepatic space, subphrenic space, and right

kidney), abdominal wall, pelvis, and left upper

quadrant for splenic pathology. Abscesses can be

seen in these areas, including within the liver, spleen,

and kidney, with a 90% to 98% accuracy.141

Ultrasonographic signs of acalculus cholecystitis in

a patient with sepsis/SIRS include pericholecystic

fluid, gall bladder distension and wall thickening,

and intrahepatic duct dilation and the absence of

stones.142

Other abdominal areas are less well seen because

of bowel gas and surgical dressings; other patient

variables such as obesity can also limit the study.

Depending on accessibility, ultrasound-guided percutaneous drainage of a fluid collection can be performed to determine its composition, or can at times

be used as an alternative to surgical drainage of an

abscess.

Computerized Tomography

Imaging of the patient with sepsis, particularly if

the patient also has had trauma, is probably best

performed with CT. Inherent in this study is the

need to transport the patient with all accompanying

life support equipment to the machine in other

areas of the hospital. Transporting for elective

procedures—to the CT scanner in particular—have

a high incidence of mishaps.143

In a study144 of 20 patients in the ICU who received routine, portable chest roentgenograms,

researchers found that in 15 (75%) of them, a thoracic CT scan was helpful in determining treatment

plans. Another study145 found clinically significant

lesions such as pneumothorax and pulmonary or

mediastinal abscesses. The overall accuracy of radiographic studies in diagnosing intraabdominal

pathology has been shown to be about 76%. The

most accurate diagnostic study appears to be the CT

scan, with sensitivity and specificity in diagnosing

an abdominal source of infection reported at approximately 90%.145 The accuracy of diagnosis by

ultrasound and radioactive gallium scan is lower

than with CT scanning.146 Diagnostic accuracy with

CT scanning improves with the addition of oral and

perhaps intravenous contrast.

Abdominal examinations should include the pelvis because fluid collects in the cul-de-sac or the

retrovesicular spaces. CT scans have proven beneficial in diagnosing empyema and abdominal abscesses, postoperative pancreatitis, bile leakage, or

delayed hemorrhage from trauma or surgical procedures.139 The CT has been used in a similar—and

at times, more successful—fashion than ultrasound

in guiding needle aspiration or percutaneous drainage of fluid collections. With the exception of case

reports, there is no literature indicating that magnetic resonance imaging (MRI) is a useful diagnostic tool in the patient with sepsis/SIRS.

Surgical Reexploration

Abdominal injuries are frequent in combat casualties. Thus, abdominal infections are a significant

possibility during the recovery phase following the

initial laparotomy. Reoperation or intervention
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

629

after abdominal surgery during the same hospitalization may be the only therapeutic intervention

that can successfully treat a patient with sepsis

whose condition is deteriorating. The indications

for reoperation have changed little over the past 60

years and include the need to eliminate or remove

the source of infection, remove infectious exudative

material, perform intraperitoneal lavage to attempt

to reduce the infective organism load, and drain an

abscess sufficiently. Most reoperations are performed for peritonitis (45%), mechanical ileus (29%),

postoperative bleeding (17%), and miscellaneous

causes (9%), including a second acute process such

as gangrenous cholecystitis, wound dehiscence, or

acute bowel ischemia.147 The mortality of patients

undergoing reexploration is approximately 43%:

the lowest mortality in one series146 was found in

trauma patients; the highest, in the patients undergoing evaluation for MODS who did not have a

treatable finding at the time of laparotomy.

Evaluation of the patient prior to reoperation

requires a thorough physical examination. More

than 85% of patients who prove to have an abnormality at laparotomy have tenderness, fever, and

absent bowel sounds.146 These findings can be misleading in the sedated patient or the patient with

mental status changes. The decision to reexplore

can be made in most patients solely on clinical

grounds. In addition to the clinical examination,

radiographic studies can be beneficial when deciding whether to reexplore a patient with sepsis. A

1985 review148 of the indications and results of

reoperation for sepsis found that no patient without

organ failure died, and that the risk associated with

a normal exploration was outweighed by the potential of finding drainable intraperitoneal pus.

The etiology of postoperative peritonitis is most

commonly (54%) secondary to an abdominal abscess.146 The second most frequent cause (16%–39%) is

a suture leak.146,147 Other causes include necrotic

bowel and technical error at the first operation.

The need for reexploration depends largely on

the patient’s clinical examination and hospital

course. Additional beneficial information can be

gleaned from radiographic evaluation, principally

the CT scan. Although mortality rates from

reexploration have not dropped significantly, current critical-care management has allowed more

patients to tolerate such a procedure.146,147 Early

intervention in a surgically reparable disease process will perhaps lead to lower reoperative morbidity and mortality.

THERAPEUTIC MODALITIES

The primary issue in resuscitation for shock of

any type, including septic shock, is to preserve

adequate oxygen delivery to the tissues. Simple

fluid administration may accomplish this in the

volume-depleted patient as a result of increasing

venous preload and thus optimizing the cardiac

stroke volume.

Although the patient’s clinical condition should

be monitored (eg, mental status, mucous membranes, and urinary output), a more accurate means,

particularly with a pulmonary artery catheter, may

be desirable. However, the limitations of both the

use and the interpretation of these data must be

considered.

Fluid Resuscitation

Intravascular volume is decreased in patients

with septic shock for the many reasons previously

discussed. Increased vascular permeability markedly increases fluid and protein transport into the

interstitium.149 This absolute intravascular fluid

loss, coupled with any additional loss from trauma

or surgery, is aggravated by a redistributive loss

due to the systemic vasodilation of septic shock.

Volume resuscitation, ideally with the aid of

hemodynamic monitoring, should be the initial

therapeutic intervention in the unstable patient in

septic shock. However, the following facts must be

kept in mind:

• Sepsis alters the normal response to volume infusion.

• Myocardial function is depressed in septic

shock.

In these patients, volume infusion has been shown

to result in only a minor increase in left ventricular

end diastolic volume and stroke work when compared to other critically ill patients who do not have

sepsis.79 Thus, many patients with sepsis have a

blunted ability to either dilate or increase ventricular contractility in response to volume infusion.

One therapeutic strategy is to increase the PCWP,

using 250-mL fluid boluses, until the cardiac index

fails to increase further. In patients with septic

shock, the PCWP associated with this maximal

preload is approximately 10 to 14 mm Hg.150 It is the

choice of resuscitation fluid in the bolus—crystalloid

or colloid—that remains controversial (Table 24-1).
Anesthesia and Perioperative Care of the Combat Casualty

630

TABLE 24-1

FACTORS IN FLUID SELECTION

Factor Crystalloid Colloid

Cost Inexpensive Expensive

Peripheral edema Significant Minimal

Anaphlyactoid reaction Absent Small risk

(< 2%)

Colloid osmotic pressure Decreases Increases

Amount needed to main- Large Small

tain intravascular volume

enous albumin or other colloids are administered.

Its molecular mass ranges from 66,000 to 69,000

daltons and has a strong negative charge at physiological pH levels. Albumin is a major transport

protein for metals, drugs, hormones, enzymes, fatty

acids, amino acids, and bilirubin.151,152

Albumin is the major oncotically active protein

in plasma, providing approximately 80% of the

colloid osmotic pressure. The normal serum albumin is approximately 3.5 to 5.0 g/dL, with 40% of

the body’s albumin located in the intravascular

space.152 Extravascular stores are largest in the skin,

but are also located in muscle and viscera. Only

free, non-tissue-bound, interstitial-space albumin

is able to return to the intravascular compartment via the lymphatic system in response to

hypovolemia.151

In response to hemorrhage, albumin synthesis

increases and its degradation or metabolism decreases. Mobilization of extravascular stores helps

to minimize the loss in oncotic pressure. However,

under severe stress, as in sepsis, albumin synthesis

falls and the colloid osmotic pressure subsequently

follows.

Exogenous albumin can be administered as either a 5% or a 25% solution. The 5% solution

contains 50 g of albumin per liter of physiological

saline and is isooncotic. The 25% solution contains

12.5 g of albumin in 50 mL of a buffered diluent that

contains 130 to 160 mEq of sodium per liter.152 When

100 mL of the hyperoncotic 25% solution is administered, the intravascular volume increases during

the next 30 to 60 minutes to a maximum of 450 mL

through the translocation of 350 mL of interstitial

fluids. Hence the use of the hyperoncotic solution

may be most beneficial in the intravascularly deCrystalloid Solutions

Crystalloid solutions can pass through a semipermeable membrane; colloid solutions cannot. The

cheapest and most commonly used crystalloid resuscitation fluids are isotonic saline solutions, principally normal saline (0.9% sodium chloride) and

Ringer’s lactate (Table 24-2). These fluids distribute

throughout the extracellular space. In normal, healthy

adults, only 25% of the volume infused remains in the

intravascular space after 1 hour. In the critically ill

patient, however, less than 20% remains intravascular.150 (Because 5% dextrose in water distributes

throughout the total body water space, it is not

effective in increasing intravascular volume.)

Isotonic saline and Ringer’s lactate can be used

interchangeably if the electrolyte differences are

kept in mind. The theoretical concern of a hyperchloremic acidosis from the administration of large

volumes of normal saline is not of clinical significance except in patients with severe renal insufficiency. Also, the administration of lactate in Ringer’s

solution does not potentiate an existing lactic acidosis or alter blood lactate measurements.151,152 The

rare exception is a patient with severe hepatic insufficiency who cannot metabolize lactate.

Colloid Solutions

Albumin. Albumin is the primary colloid used in

the volume resuscitation of patients with sepsis. It

is a natural protein of 584 amino acids synthesized

in the liver at a rate of 130 to 200 mg/kg/d in

healthy adults.151 Albumin synthesis is regulated in

part by colloid osmoreceptors located in the interstitial spaces near the sites of hepatic synthesis.152

This may be of therapeutic significance when exogTABLE 24-2

COMPOSITION OF CRYSTALLOID SOLUTIONS

Component Normal Saline Lactated Ringer’s

Sodium 154 mEq/L 130 mEq/L

Chloride 154 mEq/L 109 mEq/L

Potassium 0 4 mEq/L

Calcium 0 3 mEq/L

Lactate 0 28 mEq/L

Osmolality 308 mOsm/L 275 mOsm/L

pH 6.0 5.1
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

631

pleted patient with elevated total body water or

edema. The 5% solution is often used in initial

volume resuscitation of the hypovolemic patient

without edema.

Albumin is safe when used properly. Albumininduced anaphylaxis occurs at a rate of only 0.47%

to 1.53%; the reactions are generally mild, consisting of fever, chills, and urticaria. No infectious risk

of hepatitis or human immunodeficiency virus is

associated with its use secondary toprolonged heatkilling processing.151 One major drawback to the

use of albumin is its cost, which is approximately

30-fold greater than that of crystalloid fluids.

Hetastarch. Hydroxyethyl starch (hetastarch) is

another colloid commonly used to treat hemorrhagic shock. This compound is a synthetic colloid

composed of amylopectin that resembles glycogen.

It is available in 500-mL containers of a 6% solution

with an average molecular mass of 69,000 daltons

(range 10,000–1,000,000) and an osmolarity of 310

mOsm/L.151 After administration, smaller-molecular-weight molecules are cleared rapidly in the urine,

whereas larger molecules require amylase hydrolysis before they can be excreted in the urine or bile.152

Delayed excretion occurs because of (a) the necessary breakdown of the larger molecules and (b)

tissue absorption, most notably in the reticuloendothelial system. In normal volunteers, approximately one half the hetastarch is eliminated in the

urine within 2 days.151

The plasma-volume expansion that occurs with

hetastarch is roughly equivalent to that of 5% albumin.151 Hetastarch is not immunogenic and does

not cause a histamine release, although minor anaphylactic reactions can occur with an incidence of

less than 0.085%.151,152 Minor alterations in coagulation studies appear to be dose dependent and are

not associated with clinical bleeding, in patients

without a bleeding diathesis, in a dose less than

1,500 mL/d. Transient thrombocytopenia and prolonged prothrombin and activated partial thromboplastin times are the three abnormalities that have

been noted.151

Because its major route of elimination is via the

kidney, patients with renal impairment are at increased risk of volume overload and tissue accumulation if hetastarch is used for volume resuscitation.

Amylase levels will rise, commonly to 2-fold higher

than normal values, after its administration. These

raised levels may persist for 5 days, although no

change in pancreatic function occurs.151

Despite these few side effects, hetastarch remains

a safe and viable option for colloid volume resuscitation in the patient with sepsis. Its major advantage over albumin is that it costs approximately one

fourth as much as an equivalent amount of 5%

albumin (Table 24-3).

Selection of Resuscitation Fluid

Which of the two classes of fluid should be used

for volume resuscitation remains controversial.

However, proponents of either agree on several

points153:

• Colloid solutions more efficiently replace

blood volume than crystalloids.

• Colloid solutions are more expensive.

• Crystalloid solutions cause no anaphylactoid reactions.

• Both types of fluid are more readily available than blood, and should be used initially in the management of hemorrhagic

shock as the patient will tolerate anemia

better than hypovolemia.

• Colloid therapy provides a more effective

maintenance of colloid osmotic pressure.

• Regardless of the fluid selected, fluid overload is to be avoided.

It seems quite clear that patients with septic

shock have a heightened potential for extracellular

fluid sequestration, compared with trauma patients

who are not septic. No doubt this is caused by the

capillary membrane damage that results from the

sequential interaction of endogenous mediators and

cells in SIRS.154 The circumstances under which

TABLE 24-3

COMPARISON OF COMMERCIAL COLLOID

SOLUTIONS

Albumin

Factor 5%/25% Hetastarch

Cost Expensive 1⁄4 cost

Infectious risk None None

Anaphylactoid 0.5%–1.5% < 0.08%*

reaction

Half-life < 24 h 2 d (assuming

normal renal function)

*Source for this value: Rainey TG, English JF. Pharmacology of

colloids and crystalloids. In: Chernow B, ed. The Pharmacologic

Approach to the Critically Ill Patient. Baltimore, Md: Williams &

Wilkins; 1988: 235.
Anesthesia and Perioperative Care of the Combat Casualty

632

cular membrane permeability are relatively minor,

an aberration that occurs early in sepsis.155 Nevertheless, a study that used the technique of metaanalysis concluded that, in the trauma patient with

sepsis, better survival and better resuscitation are

achieved with crystalloid solution.157

Which fluid is to be used varies with the clinical

setting. Those clinical conditions associated with

both intravascular hypovolemia and extracellular

fluid deficit are best replenished with crystalloids.

These fluids are more plentiful, less expensive, and

without anaphylactoid side effects. More volume

must be administered when compared with colloids, a condition easily tolerated in patients with

trauma and perhaps surgical patients, particularly

if they are young. Older individuals, and possibly

patients with sepsis, are at greater risk of developing pulmonary edema. However, inadvertent volume overload with crystalloid solutions is relatively short lived, due to equilibration with the

extravascular space.

A lesser volume of colloid solution is needed to

obtain the same hemodynamic parameters as crystalloids; a greater percentage remains in the intravascular space for a longer time period.

Hetastarch is cheaper than albumin and increases

colloid osmotic pressure over 3-fold that of an

equivalent volume of albumin,158 although its use

has other potential effects (discussed above). The

concern that colloid molecules pass through membranes of increased permeability, as is seen in sepsis,

thereby increasing interstitial oncotic pressure and

edema, remains speculative. Some authorities151,159

recommend using only crystalloid solutions in this

setting until the “leak” has sealed. The following

are general guidelines for the use of crystalloid and

colloid solutions:

• Colloids may be used for prompt volume

expansion, and should be used in conjunction with crystalloids when more than 30%

of the intravascular volume requires replacement.

• The total volume of crystalloid used and

perhaps the subsequent development of

interstitial edema may be minimized by

concomitant administration of albumin or

hetastarch to maintain colloid oncotic pressure.

• In the setting of increased total body water

or edema, 25% albumin should be used.

• Volume overload must be monitored because colloids remain for a prolonged time

within the intravascular space.

these pathophysiological differences may become

clinically relevant are not the only factors that need

to be considered when the choice of fluid is discussed. Additional areas of debate in the use of

these two fluids are whether there is a significant

difference in their effects on the patient’s coagulation, renal function, pulmonary interstitial water,

development of ARDS, length of stay in the hospital

or ICU, and survival.153 The answers to these clinical questions should determine whether continued

use of colloid fluids is warranted in light of the cost

and potential side effects.

The main reason for using colloids is to prevent

pulmonary edema. The amount of pulmonary

edema that forms depends on (a) microvascular

hydrostatic pressure (estimated by the PCWP), (b)

colloid osmotic pressure, and (c) permeability of the

alveolar-capillary membranes. The role played by

hydrostatic pressure is more important than that of

colloid osmotic pressure. The low colloid osmotic

pressure seen with hypoalbuminemia does not, in

and of itself, lead to pulmonary edema. The development of pulmonary edema is encouraged when

capillary permeability is altered, for increased hydrostatic pressure results in increased transudation

of fluid into the interstitial space. One concern with

colloid infusions in this setting is that increasing

protein, and hence oncotic pressure in the

interstitium, will worsen edema. This hypothesis,

however, remains to be definitively confirmed.155

Most studies comparing colloids and crystalloids

have occurred in the setting of surgery, thermal

burns, or trauma. One study compared the cardiorespiratory effects of treating patients in circulatory

shock with 5% albumin, 6% hetastarch, or 0.9%

saline.156 Over two thirds of the patients studied

were in septic shock; the remainder were in hypovolemic shock. Their median age was 79 years. All

three solutions were found to provide the same

cardiac function and hemodynamic stability. Neither albumin nor hetastarch depressed myocardial

function. Hetastarch and albumin were of equivalent efficacy in treating circulatory shock. To attain

the same physiological end points, 2- to 4-fold more

crystalloid solution was required. Saline administration decreased the colloid osmotic pressure as

expected. When the patients were resuscitated to

the same physiological end points, the crystalloid

solution caused an increased incidence of pulmonary edema compared with the two colloids.155

These results were, however, a summation of the

effects seen in patients with sepsis and patients in

hypovolemic shock. In studies of patients who do

not have sepsis, alterations in capillary, microvas-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

633

• Little additional benefit is gained in intravascular colloid osmotic pressure when the

pressure is greater than or equal to 20 mm

Hg, the serum albumin is greater than or

equal to 2.5 g/dL, or the total serum protein is greater than or equal to 5.0 g/dL.

Tissue Oxygen Delivery and Consumption

Tissue oxygen delivery (DO2) is a function of cardiac output (C.O.) and arterial oxygen content (CaO2):

DO2 = C.O. • CaO2

Arterial oxygen content is a function of hemoglobin (Hb) concentration and the degree of oxygen

saturation of the blood (SaO2), the latter being determined by the partial pressure of oxygen (PO2):

CaO2 = 1.34 • grams of Hb • SaO2 + 0.003 • PO2

Tissue oxygen consumption (VO2) can be calculated as the difference between the arterial (CaO2)

and venous (CvO2) oxygen contents multiplied by

the cardiac output (C.O.):

VO2 = C.O. • (CaO2 – CvO2)

If tissue oxygen delivery is inadequate or if tissue

oxygen extraction is abnormal, all three factors—

cardiac output, hemoglobin, and oxygen saturation—must be optimized.

Cardiac Index

Optimal left ventricular preload has been described

previously in this chapter. Less is known concerning

the optimal cardiac index for patients with sepsis or

septic shock. Most patients with sepsis or septic shock

manifest an elevated cardiac index as the principal

compensatory mechanism by which tissue oxygen

delivery is increased to meet demand.

Increased survival in patients with sepsis whose

cardiac outputs are higher than normal has been demonstrated.160–162 In a study160 comparing critically ill

patients after surgery, the variables that showed the

greatest statistical discrimination between survivors

and nonsurvivors were left ventricular stroke work,

oxygen delivery, and oxygen consumption.

Hemoglobin

Hemoglobin is the major determinant of the oxygen content of arterial blood. One gram of hemoglobin increases arterial oxygen as much as increasing the partial pressure of arterial oxygen (PaO2)

from 100 to 400 torr. This is because hemoglobin

oxygen saturation is close to 100% at a PO2 of 100

torr. A higher PO2 increases oxygen content only

slightly because the added oxygen is carried dissolved in the plasma and constitutes only about 2%

of the total oxygen being carried. The optimal

hematocrit for patients with sepsis is not known.

The conventional wisdom has been than a hematocrit between 0.30 and 0.40 provides the maximum

oxygen delivery if all other factors are held constant. This is based on clinical studies that show

increased viscosity, decreased cerebral blood flow,

and increased incidence of vascular occlusive episodes when the hematocrit exceeds 0.45. Despite a

calculated increase in the arterial oxygen content

that would result from transfusion of packed erythrocytes, in patients with septic shock, significant

increases in systemic oxygen consumption are not

apparent.162 The explanation may be a reflexive

decrease in cardiac output.

A clinical study that was published in 1993 also

showed that transfusion of packed red cells did not

cause an increase in systemic oxygen consumption,

even though cardiac index did not change.163 As

part of this study, gastric intramucosal pH was

also measured. The pH fell after the transfusion,

and the magnitude of the decrease was directly

related to the age of the blood. The researchers

suggest that (a) the ability of erythrocytes to deform

(ie, to fold, which enables them to pass more easily

through capillaries—a capacity that is known to be

decreased in aged blood) was reduced in aged blood,

and (b) this factor depressed tissue oxygen availability.

Arterial Saturation

Arterial oxygen saturation depends on the partial pressure of dissolved oxygen and the position

of the oxyhemoglobin dissociation curve; specifically, the point on the dissociation curve where the

hemoglobin is 50% saturated (P50). Fresh red blood

cells have a higher P50 than bank blood that has

been stored for several weeks, and therefore might

be expected to display more-favorable oxygen-unloading characteristics.164 Nevertheless, although

shifts of the hemoglobin saturation curve occur

under many clinical situations (eg, P50 is decreased

by hypothermia or alkalosis but is increased by

hyperthermia or acidosis), there is virtually no evidence in the literature that this results in a clinically

significant change in tissue oxygen delivery.
Anesthesia and Perioperative Care of the Combat Casualty

634

*

Critical Oxygen Delivery

In well individuals, a biphasic relation exists

such that when oxygen delivery is decreased to a

critical point (approximately 8–10 mL/kg/min),

oxygen consumption falls. Above this critical level,

oxygen consumption remains constant and independent of oxygen delivery. However, this relation

may not be true for patients with sepsis/SIRS or

MODS. Many studies150,165–167 indicate that in these

patients, either the critical level of oxygen delivery is

much higher or a definable critical level is lost (Figure

24-9). As a result of this change in physiology, tissue

oxygen utilization may become “supply dependent”

and, although the utilization is greater than normal,

it may actually be associated with cellular hypoxia.

This is suggested by the frequent presence of elevated plasma lactate levels. A number of explanations have been proposed for the paradoxical coexistence of elevated oxygen delivery and apparent

hypoxia (Exhibit 24-5). These explanations fall into

two categories: (1) abnormalities in blood flow at

the level of the microcirculation and (2) deranged

cellular metabolism.

Oxygen Delivery

Fig. 24-9. This schematic drawing shows the relation

between oxygen consumption and oxygen delivery in

normal humans and in patients with sepsis. In normal

humans, oxygen consumption does not increase once a

certain level of delivery is reached; it remains essentially

constant and independent of delivery. This phenomenon

is indicated by (*). In patients with sepsis, however, a

similar phenomenon is not seen: oxygen consumption

continues to increase as oxygen delivery increases.

EXHIBIT 24-5

FACTORS CONTRIBUTING TO SUPPLY-DEPENDENT TISSUE OXYGEN UTILIZATION

1. Mitochondrial cellular respiration is inhibited (there are no clinical human data).

2. Decreased VO2 is a protective mechanism to prevent organ damage (this has been disproved in cerebral

ischemia model).

3. The phenomenon is simply the result of mathematical coupling (this is probably not true because the

correlation between VO2, as measured directly by gas analysis, is well correlated with the value calculated by the Fick equation, and the VO2–DO2 correlation appears “linked” in septic patients but not in

control groups).

4. A disproportionate percentage of the cardiac output may be delivered to organs with low metabolic

demands and oxygen extraction (eg, skin and muscle).

5. Arteriovenous shunts may occur in the precapillary tissue beds.

6. There is a maldistribution of microcirculatory flow as a result of the following factors:

• microembolization or microthrombi blocking the peripheral vascular bed,

• endothelial injury and tissue edema increasing the membrane thickness through which oxygen must

diffuse,

• leukocyte aggregation blocking the peripheral vascular bed,

• altered erythrocyte deformability,1

 and

• endogenous mediator-induced vasoconstriction reducing flow of the tissue vascular beds.

1

Hud TC, Dasmahapatia KS, Rush BF, Machiodo GW. Red blood cells deformability in human and experimental sepsis. Arch

Surg. 1988;123:217–220.

Sepsis

Normal

Oxygen Consumption

*
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

635

Most animal studies support the concept that

shunting blood flow past tissue beds is frequently

secondary to the factors listed in Exhibit 24-5. Shunting of blood from the visceral organs to the skin is

evident in patients with sepsis, who have vasodilated and warm skin in the presence of oliguria.

Because the skin has very little metabolic need and

thus extracts little oxygen, the saturation of venous

blood returning to the heart (mixed venous oxygen

saturation) remains higher than normal.

Many important questions remain unanswered.

What causes shunts to open in the skin? Why is the

increased cardiac index that characterizes septic

shock in humans not adequate to simultaneously

perfuse both the skin and the visceral organs? Furthermore, although open shunts at the microcirculatory level in viscera would allow blood to bypass

nutrient pathways at the cellular level, there is little

evidence that such shunts open. However, it is

possible that blood flow at the microcirculatory

level in a given organ might be maldistributed in a

manner similar to that seen when ventilation and

perfusion are mismatched in the lung.

The metabolic abnormalities that occur in sepsis/

SIRS may arise at the cellular level. Perhaps endogenous mediators impair metabolic pathways in the

Krebs cycle, leading to the need for augmented

formation of adenosine triphosphate through glycolysis. Experimental and clinical evidence does not

provide convincing support for this explanation, for

neither the cellular high-energy phosphate levels nor

the ratio of the concentrations of pyruvate and

lactate are consistently abnormal in either humans

or experimental animals with severe sepsis.168

A number of studies (some of which confirm,

others which do not) demonstrate the presence of

abnormal oxygen-supply dependency during septic shock. The reason for the conflict in results is not

known; however, this difference may be the result

of the heterogeneous population of patients who

develop septic shock and the great variety of metabolic demands that may be associated with the

septic shock syndrome. If a defect in oxygen utilization does exist, it probably results from tissue

hypoperfusion secondary to microcirculatory flow

abnormalities.

Lactic Acidosis

The usual cellular response to hypoperfusion is

anaerobic metabolism; lactic acidosis may develop

as a consequence. However, it is important to

recognize that lactate, not lactic acid, is the product

of anaerobic glycolysis, and it is the breakdown of

adenosine triphosphate, not its formation, that generates hydrogen ions.

Lactate levels are most accurately assessed

through an arterial sample so that focal limb

hypoperfusion does not affect the sample. Frequent

monitoring of the lactate level in the patient with

sepsis may yield information regarding the severity

of disease,169 the possible presence of oxygen-supply dependency, the response to therapy (particularly volume administration),170 and the patient’s

prognosis.170,171 Decreased survival has been documented in critically ill patients who have arterial

lactate levels greater than 2.0 mmol/L.172 Both the

initial and the subsequent degree of reduction of

the lactate levels have been used as prognostic

indicators: a study170 published in 1991 of 48 patients in septic shock documented the superiority of

blood lactate levels over oxygen-derived variables

in estimating the patient’s prognosis.

The monitored variables discussed above (DO2,

VO2, and lactate level) are probably best used in complement to aid the physician’s decision making regarding therapeutic responses and ultimate prognosis.

Inotropic and Vasopressor Drugs

Not infrequently, the profound vasodilation that

occurs in sepsis causes refractory hypotension despite adequate volume resuscitation. Inadequate

tissue perfusion that occurs as a result of hypotension

will exacerbate organ damage and thus must be

corrected. Although inotropic and vasopressor medications are commonly used, few studies compare the

efficacy of these agents in the treatment of septic

shock. In contrast to cardiogenic shock, for which

the selection of a drug with α-agonist properties is

undesirable, sepsis-induced vasodilation often demands the use of a drug with significant effect on

vascular tone. For example, amrinone lactate causes

vasodilation predominantly, making this agent a

poor choice for sepsis-induced hypotension unless

the patient also has myocardial depression. Table

24-4 lists the characteristics of several commonly

used vasopressor/inotropic drugs.

At one time, the use of norepinephrine was

shunned because physicians feared that peripheral

vasoconstriction, digital ischemia, and renal insufficiency would ensue. Using a canine septic model,

researchers demonstrated that the addition of lowdose dopamine (4 μg/kg/min) caused an increased

level of renal blood flow whenever norepinephrine

was used.173 The use of norepinephrine has recently

been reappraised, particularly in patients with shock

refractory to dopamine. One study174 reported a
Anesthesia and Perioperative Care of the Combat Casualty

636

TABLE 24-4

CHARACTERISTICS OF USEFUL INTROPES AND VASOPRESSORS

DOP DOB EPI NOR AMI

Alpha selectivity ++ – +++ ++++ –

Renal vasodilation ++ – – – –

Tachycardia ++ + +++ – +

Dysrhythmias ++ + +++ – +

Dosage (μg/kg/min)* 2–20 4–20 0.01–1.0 0.01–1.0 5–20

*Dosages listed are the standard range for patient treatment, and do not infer a maximum safe dosage

DOP: dopamine in moderate dose range (5–10 μg/kg/min); DOB: dobutamine; EPI: epinephrine; NOR: norepinephrine; AMI:

amrinone

40% incidence of dopamine resistance in 29 patients

in septic shock. The addition of norepinephrine

infusion reversed the shock in 10 of 12 (83%) patients. Another study175 reported a 100% success

rate in reversing hypotension in 10 patients with

intractable septic shock.

The fear that potential renal insufficiency and

decreased tissue blood flow will result from using

norepinephrine has been shown to be unfounded.

Five studies175–179 evaluating renal function following the use of norepinephrine for refractory

hypotension and oliguria in septic shock are reviewed in Table 24-5. One notable study179 indicates that patients with a persistent perfusion deficit, as evidenced by lactic acidemia, did not demonstrate an improvement in renal function

following the administration of norepinephrine.

Support of the Respiratory System

As discussed earlier in this chapter, respiratory

insufficiency is common in patients with sepsis.

Although the patient may be able to maintain an

adequate level of arterial oxygenation, the increased

TABLE 24-5

NOREPINEPHRINE IN REFRACTORY SEPTIC SHOCK

No. of Patients Success Rate Urinary Output* Creatine Clearance* Survival

251 100% I (100%) I (100%) 16⁄25 (64%)

52 100% I (100%) N/A 2⁄5 (40%)

63

 (elevated lactate) 100% NC D (100%) 0

93 (normal lactate) 100% I (100%) NC 4⁄9 (44%)

244 100% I (83%) I (83%) 16⁄24 (67%)

105 100% I (100%) N/A 4⁄10 (40%)

*The incidence in which the target blood pressure was achieved with norepinephrine

NC: no change; N/A: not measured; I: increased; D: decreased

Data sources: (1) Desjars P, Pinaud M, Bugnon D, Tasseau F. Norepinephrine therapy has no deleterious renal effects in human septic

shock. Crit Care Med. 1989;17(5):426–429. (2) Hesselvik JF, Brodin B. Low-dose norepinephrine in patients with septic shock and

oliguria: Effects on afterload, urine flow, and oxygen transport. Crit Care Med. 1989;17(2):179–180. (3) Fukuoka T, Nishimura M,

Imanaka H, Taenaka N, Yoshiya I, Takezawa J. Effects of norepinephrine on renal function in septic patients with normal and

elevated serum lactate levels. Crit Care Med. 1989;17(11):1104–1107. (4) Martin C, Eon B, Saux P, Aknin P, Gouin F. Renal effects of

norepinephrine used to treat septic shock patients. Crit Care Med. 1990;18(3):282–285. (5) Meadows D, Edwards JD, Wilkins RG,

Nightingale P. Reversal of intractable septic shock with norepinephrine therapy. Crit Care Med. 1988;16(7):663–666.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

637

work of breathing and the corresponding increased

oxygen consumption may be harmful. Earlier studies have shown that during respiratory failure, blood

flow to the diaphragm may approach 20% of the

total cardiac output, compared with the normal 3%

to 5%, potentially depriving other tissues of necessary oxygen delivery. Additionally, oxygen utilization of the respiratory muscles alone may account

for up to 25% of the total oxygen consumption.180

Although it remains unproven, the institution of

mechanical ventilation may reduce systemic oxygen consumption and thus aid in clearing lactic

acidosis. The clinician must ensure that hypovolemia has been treated because the institution of

positive pressure ventilation may cause a decrease

in both venous return and cardiac output.

Antimicrobial Therapy

Although the diagnosis of sepsis may be elusive,

once considered, therapy must begin early and

decisively. This treatment includes excision,

debridement and drainage of abscesses or focal

sites of infection, and the restoration of a volume

deficit. Adequate tissue oxygen delivery, support

of organ dysfunction, and the initiation of antimicrobials181 are the primary therapeutic goals.

The most common category of wound sustained

in combat involves only the soft tissue of the body

(skin, fat, and skeletal muscle)—wounds that are

infrequent sources of fatal sepsis when treated following the established principles of military surgery. However, wounds that involve deeper structures such as bones and especially intraabdominal

viscera, even given state-of-the-art surgical care,

have a high likelihood becoming infected, with the

possibility of inducing sepsis (45% of open comminuted fractures of the femur become infected,182 as

did 45% of open comminuted fractures of the tibia,183

and 50% of colonic wounds184).

Nosocomial infections, though, are common in

traumatized patients and are significant potential

causes of sepsis.181 In these instances, antimicrobial

therapy can be directed at the identified or presumed

pathogens. However, in those cases of generalized

sepsis without an identified source, or those with

several possible sources, antimicrobials—particularly

antibiotics—must be initiated early and broadly

enough to cover a variety of potential pathogens.

Selection of Antimicrobial Therapy

Ideally, the infecting pathogen should be identified before antibiotic therapy is started. This requires identification through culture, a process that

delays initiating therapy. Specific clues as to the

organisms may be gleaned from the physical examination and Gram’s stain of material from potential

pathogenic sites. Examination of the skin may be of

significant benefit, as it allows infections in surgical

wounds, venipuncture sites, or intravenous catheter sites to be identified. Pathognomonic lesions

from meningococcemia, toxic shock syndrome, or

infectious endocarditis may also be identified.185

All potentially infected materials such as blood,

urine, sputum, wound exudate, and cerebrospinal

fluid should be examined and cultured based on the

patient’s condition.186 Cultures and Gram’s stains

require proper handling to prevent contamination

and potential misinterpretation. Additional diagnostic studies such as CT scan may help identify a

potential source of infection. Not uncommonly,

though, critically ill patients cannot undergo the

optimal diagnostic procedure. They may be too

hypoxic for a bronchoscopy, too thrombocytopenic

for a tissue biopsy, or too unstable for transport to

the radiology department or operating room.187

After all diagnostic measures have been completed, specific treatment aimed at the isolated

pathogen should begin. Often, however, the initial

therapy is nonspecific, pending identification of the

responsible pathogen. When selecting an antibiotic, some of the many factors that must be considered include the following185,186:

• onset of infection (traumatic, communityacquired, or nosocomial),

• assumed infective focus,

• immunological status of the patient,

• underlying diseases,

• accompanying organ failure,

• previous antibiotic treatment,

• pharmacokinetics and toxicities of the antibiotics, and

• epidemiology of isolated organisms at the

institution, including patterns of resistance.

Ideally, the chosen antibiotic regimen is well tolerated by the patient, is bactericidal, has minimal side

effects, and covers all potential pathogens for the

particular patient. Antibiotics must be given early,

in sufficient dosages, and usually parenterally186 in

the critically ill patient.

Bacterial Infections. Although Gram-negative

infections are well known for producing sepsis/

SIRS, Gram-positive organisms can also cause it.

Immunocompetent patients are often infected with

a single pathogen. Immunocompromised patients,
Anesthesia and Perioperative Care of the Combat Casualty

638

however, are frequently infected with many different organisms; hence, they require broad antibiotic

coverage. Broad, initial antibiotic coverage is ideally narrowed to more-specific, less-toxic antibiotics after culture results are obtained. Such measures minimize drug toxicity, lower costs, reduce

the incidence of superinfection, and lower the development of antibiotic resistance.185

After a thorough diagnostic evaluation, empirical treatment is usually based on the presumed site

of infection. Nosocomial pneumonias are usually

caused by resistant, aerobic, Gram-negative rods,

particularly Pseudomonas species. Treatment includes an antipseudomonal penicillin (mezlocillin,

ticarcillin, or piperacillin) or an effective cephalosporin (ceftazidime) in combination with an

aminoglycoside. Cephalosporins with activity

against Enterobacteriaceae from the lung and other

sites include cefotaxime, ceftizoxime, and ceftriaxone.151 Other bacterial causes of nosocomial

pneumonia are Legionella, which is treated with

erythromycin; Staphylococcus aureus, which, depending on whether the microorganism is methicillin-resistant or penicillinase-producing, can be

treated with methicillin, vancomycin, or a cephalosporin such as cephalothin or cefazolin; and the

anaerobic organisms, which are treated with

clindamycin or metronidazole. However, imipenem/

cilastatin, a combination of a carbapenem and a

metabolic inhibitor (Primaxin, manufactured by

Merck, Sharp and Dohme, West Point, Pa.), is a

more recent and possibly a better choice.

Urosepsis is usually caused by Gram-negative

rods or enterococci and can be treated with ampicillin (or vancomycin in the penicillin-allergic patient) and an aminoglycoside. Enterobacteriaceae

can be treated as above.

Peritonitis or intraabdominal infections are

polymicrobial and include enteric Gram-negative

rods and anaerobes. Initial treatment includes an

aminoglycoside and metronidazole or clindamycin,

with the addition of ampicillin or vancomycin for

enterococci.

Cellulitis is caused by streptococci or staphylococci and can be treated with a first-generation

cephalosporin (such as cefazolin), oxacillin, or

vancomycin. Sepsis associated with an intravenous

catheter is caused by Staphylococcus aureus, Staphylococcus epidermidis or Gram-negative rods and will

respond to treatment with vancomycin, an appropriate cephalosporin or, in the case of Gram-negative rods, an aminoglycoside.

Outpatient meningitis, which is often seen in

troop populations that are in close confines (eg, in

barracks), is caused by Streptococcus pneumoniae or

Neisseria meningitidis, and can be effectively treated

with high-dose penicillin. Meningitis seen after

trauma requires treatment for (a) Gram-negative

infections, with a third-generation cephalosporin

such as cefotaxime or ceftriaxone, or (b) Staphylococcus aureus, with vancomycin.

Usually the initial therapy of sepsis consists of a

β-lactam antibiotic and an aminoglycoside. The βlactams include the penicillins and cephalosporins

as well as the newer carbapenems and monobactams.

These agents may be combined with β-lactamase

inhibitors such as clavulanic acid or sulbactam.186

Quinolones are also potentially beneficial. The antibiotics with the broadest aerobic Gram-negative,

Gram-positive, and some anaerobic coverage are

imipenem/cilastatin and ticarcillin/clavulanate

(Timentin, manufactured by SmithKline Beecham,

Pittsburgh, Pa.). These are often held in reserve for

severe septic infections or in those cases where the

etiologic septic focus is unclear and a simplified,

less-toxic antibiotic regimen is required. Aztreonam

is a monobactam active only against Gram-negative

strains and at times may provide an alternative to

aminoglycosides.

Lastly, the quinolones are emerging as a potential complement to the regimen in treating patients

with sepsis, particularly as resistance to other antibiotics appears. Ciprofloxacin from this group has

displayed activity against Enterobacteriaceae,

Legionella species, Campylobacter species, Yersinia

species, Staphylococcus aureus, Hemophilus species,

and Pseudomonas aeruginosa.

186

Appropriately chosen antibiotics should be expected to result in patient improvement within approximately 48 hours. The patient’s failure to improve may suggest one or more of the following

problems185:

• inappropriate antibiotic selection, due either to inactivity against the pathogen or to

poor penetration into the infected site,

• inadequate dosing,

• an antibiotic-induced toxicity such as drug

fever,

• an undrained focus of infection,

• an infection such as infective endocarditis

that requires a longer time to show a clinical response, or

• infection with another pathogen not covered by the chosen antibiotic.

Nonbacterial Infections. Nonbacterial infections

can occur in the immunocompromised, septic pa-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

639

tient, particularly those on antibiotics. Fungal infections are becoming more prevalent in the compromised host. The most common pathogenic fungus is Candida, particularly C albicans. Superficial

mucosal infections are common as normal bacterial

flora are inhibited by antibiotics. Local visceral

involvement of the kidneys, lung, and central nervous system can also occur. Finally, disseminated

candidiasis with candidemia, Candida endophthalmitis, or multiorgan involvement can occur in

the seriously ill patient who is being treated with

antibiotics.

The source of Candida is usually the patient’s own

gastrointestinal tract. Overgrowth occurs when

bacterial flora are reduced, and invasion occurs via

surgery, intravenous devices, or translocation across

the gastrointestinal wall.188 Disseminated disease is

notoriously difficult to diagnose, with less than one

half the patients having documented candidemia or

candiduria. Treatment of disseminated candidiasis

is with high-dose amphotericin B. Empirical

amphotericin B may become justified when adequate antibacterial therapy fails to elicit an appropriate clinical response and candidiasis is suspected.189

Infections with viruses such as herpes simplex,

varicella-zoster, and cytomegalovirus are common

in medical patients with primary or secondary immunodeficiencies, although these may also appear

in patients with sepsis or other severe illnesses. For

example, reactivation of latent herpes infections

may appear in many patients, particularly those

with burns or skin breakdown.189 Lastly, occult

tropical or parasitic diseases endemic to the theater

of operations may complicate a seriously ill patient’s

course (eg, by causing persistent fever).

Proposed Therapies

Although the high mortality for sepsis/SIRS and

septic shock is widely recognized, the disparate

definitions for sepsis and septic shock that were

used prior to the American College of Chest Physicians–Society of Critical Care Medicine Consensus

Conference contribute to the difficulty of scientific

analysis of therapeutic trials. Fluid therapy, optimization of oxygen delivery and consumption, inotropic support, and antimicrobial therapy are the

mainstay treatments for sepsis/SIRS. As we learn

more about the derangements of this syndrome and

the consequences of the disease state itself, and its

treatments, newer therapies are being discovered.

Investigational therapies have suggested evidence

of success, but their validity is not yet established;

therefore, this chapter will treat these as proposed

therapies.

Prevention of Nosocomial Pneumonia

Nosocomial pneumonia is a significant cause of

morbidity and mortality in hospitalized patients

and is particularly prevalent in mechanically ventilated patients. In the past, four causes of pneumonia have been theorized190:

1. bacterial inoculation by hematogenous

spread,

2. direct extension into the lung from a contiguous site,

3. contamination of hospital equipment, and

4. aspiration of bacteria from the stomach and

oropharynx.

Of these, the first two are thought to be rare, the

third has been implicated, and the fourth appears to

be the most common.

Bacterial overgrowth of Gram-negative organisms occurs in the stomach when the pH is increased (> 3.5–4.0).191 This occurs in patients treated

with antacids or histamine type 2 (H2) blocking

agents that are used as prophylaxis against stressinduced gastrointestinal bleeding. With this bacterial overgrowth, reflux of bacteria with subsequent

aspiration predisposes to the development of Gramnegative pneumonia.190

Sucralfate is a nonabsorbable, cytoprotective

agent that minimally neutralizes stomach acid, although it is as protective as antacids and H2 blocking agents in preventing stress ulceration.191 In

1987, researchers reported that, when compared

with gastrointestinal prophylaxis with sucralfate,

the use of antacids or H2 blocking agents or both

resulted in a 2-fold increase in the incidence of

pneumonia and a 6-fold increase in the mortality.192

These data suggest, then, that elevating gastric pH

increases the risk of nosocomial pneumonias

through increased bacterial overgrowth.

This information, however, remains controversial. Further review of these data suggest that other

factors may play a role in the development of

nosocomial pneumonias. When the use of antacids

was separated from the use of H2 blocking agents,

only the groups using antacids had the high incidence of pneumonias, whereas the patients who

received H2 blocking agents alone did not. One

suggestion is that antacids increase gastric volume,

leading to more reflux, whereas H2 blocking agents

reduce gastric volume.190 Differences in the kinds of
Anesthesia and Perioperative Care of the Combat Casualty

640

organisms found colonizing the stomach and the

lung have also been reported. One study193 reported that different pathogens were found in these

two locations 28% of the time, and 22% of the time

the organisms appeared in the trachea before they

appeared in the stomach. These data throw the

pathophysiological mechanism previously reported

into question. Thus, prophylactic gastric protection, and its relationship to nosocomial pneumonias,

remains controversial.

Selective Gut Decontamination

After 1 week in an ICU, 70% to 90% of mechanically ventilated patients become colonized with

hospital-acquired bacteria in the oropharynx,

with subsequent infection occurring in more than

60%.194 Most infections are endogenous, in the

sense that they are caused by potentially pathogenic organisms that are normal constituents of the

oral or intestinal flora at the time of the patient’s

admission to the ICU (primary endogenous infections); others are acquired from the environment

while in the ICU (exogenous infections).195 The

organisms primarily involved in the colonization

and subsequent infection are the Enterobacteriaceae,

Pseudomonas species, Acinetobacter species, and

Candida species.194,195

Infection occurs when normal host defenses break

down. Normal colonization defenses include mucous membrane integrity, normal physiology and

motility (swallowing, peristalsis, and salivation),

secretions (saliva, mucous, gastric acid, and bile),

secretory IgA, normal mucosal-cell turnover, and

indigenous anaerobic flora. The causes of the breakdown in critically ill patients include instrumentation, anesthetics and muscle relaxants, antacids and

H2 blocking agents, and antibiotics.195

Attempts to prevent infection from colonizing

organisms were first introduced in the ICU following a 1981 study involving patients undergoing

colorectal surgery, and patients who were immunocompromised, granulocytopenic, or victims of a

burn injury.196 The antimicrobial regimen most

commonly used covers all potential pathogens,

avoids indigenous (mostly anaerobic) flora, is nonabsorbable, has minimal bactericidal concentrations

for most potential pathogens, and is not degraded

by food or enzymes within the gut lumen.195 One

example of selective gut decontamination by antibiotics is the following194,195,197:

• a 10-mL suspension of 100 to 200 mg of

polymyxin E, 80 mg of tobramycin, and 500

mg of amphotericin B is administered

through a gastric tube four times daily;

• a paste containing 2% each of polymyxin E,

tobramycin, and amphotericin B is applied

to the oral mucosa every 6 hours; then

• an intravenous antibiotic is usually given

as prophylaxis for 4 days after the patient is

admitted to the ICU until most colonizing

potential pathogens are eliminated, to prevent early pulmonary infections caused by

community-acquired pathogens (the antibiotic is usually cefotaxime, 1 g administered intravenously every 6 h).

The reported results are varied. Most studies

have been performed in Europe and their results

have been reviewed and summarized recently.195

Many studies included patients who were already

infected when they were admitted, although some

studies included noninfected, traumatized patients.

Nevertheless, all studies confirmed a significant

reduction in secondary colonization and infection

of the respiratory tract. Among the general surgical

patients, although selective gut decontamination

significantly reduced the incidence of acquired infections, it did not reduce mortality. The mortality

of trauma patients was reduced, particularly among

those who were severely injured. In this population,

mortality from sepsis or MODS was almost completely prevented. The emergence of organisms resistant to the antimicrobials used did not occur.

The enteric flora controlled by this regimen may

be responsible for much of the sepsis seen in the

control population (ie, those who did not receive

the gut decontamination). Potential enteric pathogens may, theoretically, contribute to the patient’s

illness (known as “gut-origin sepsis”) through one

of three mechanisms195:

1. direct spread to contiguous organs or

through aspiration of oral or stomach flora;

2. absorption of endotoxin from enteric, aerobic Gram-negative organisms; and,

3. as demonstrated in animal studies, translocation of potential pathogens through a

permeable gut mucosa that has been impaired as a result of ischemia, shock, burns,

trauma, or endotoxin.

Although the results published to date appear to

support these theories, many questions remain to

be answered. In a study of patients with combined

acute renal and respiratory failure who received

selective gut decontamination, 10 of 12 (83%) con-
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

641

trol patients developed defined infections, compared with 5 of 15 (33%) patients who received the

regimen. However, no significant difference in

survival between the groups was seen.197 Infections

appear to be controlled with this technique, although further evaluation is necessary to determine

its indications.

Immunotherapy

As noted throughout this chapter, conventional

therapy with antimicrobials and supportive measures in the treatment of sepsis/SIRS has not appreciably reduced morbidity and mortality, particularly in the case of Gram-negative sepsis. Immunotherapy directed at causative organisms has been

evaluated as a means to improve survival. Specific

immunotherapy directed at causative organisms is

not simple, for the three common Gram-negative

organisms often implicated in sepsis have many

serotypes: Escherichia coli, approximately 150; Klebsiella species, approximately 80; and Pseudomonas

aeruginosa, approximately 17.198 Thus, less-complicated schemes have been devised and are being

investigated. It is the invasion of Gram-negative

organisms that usually initiates the series of events

that ultimately produces the sepsis/SIRS syndrome.

Immunomodulation of several of these steps has

been evaluated in an attempt to abate the septic

process at whatever stage it has reached. The areas

studied have been therapies directed against the

common pathogens; endotoxin; and the cytokines,

the end products of the sepsis process.

The use of intravenous IgG in patients with sepsis

remains controversial. Generally, in the absence of

a functional hypogammaglobulinemia, intravenous

IgG does not significantly mitigate the infectious

process.198 Some studies in patients with impaired

defense mechanisms (such as occurs in multiple

trauma or major surgery) suggest a possible therapeutic role for the use of intravenous IgG in combination with antibiotics.191,199,200 More specific antiPseudomonas immunoglobulins are being prepared

and tested.

Sepsis caused by Pseudomonas, Klebsiella, and

Escherichia coli has been found to be caused by

relatively few of their many serotypes. With this

information, in an attempt to target Gram-negative

pathogens more specifically, vaccines against these

predominant serotypes have been developed and

are being tested both as active vaccines and for use

in the induction of type-specific antibodies that

could then be used to prepare a hyperimmune intravenous immunoglobulin for passive immunotherapy. Some progress has been made with these

vaccines and they may, at some future time, be

given prophylactically to patients at risk for infection (eg, prior to elective bowel surgery) or to populations at risk for trauma (eg, soldiers).198

The most intriguing data on immunotherapy

published during the 1980s is that directed against

the lipopolysaccharide moiety of endotoxin. In

1982, researchers prepared an antiserum to endotoxin by vaccinating healthy men with the J5 mutant Escherichia coli.

201 Lacking the oligosaccharide

side chain, the lipopolysaccharide core—known as

lipid A—of this mutant, which is nearly identical to

that of most other Gram-negative bacteria, was exposed to promote antibody formation. In a controlled trial, patients with bacteremia and those in

profound shock had improved survival when treated

with the J5 antiserum, when compared with controls. Whether the factor responsible for these patients’ improvement was an immunoglobulin has

not been validated. One study that used intravenous

immunoglobulin from donors immunized with a J5

vaccine failed to replicate these results.202

More recently, a human monoclonal IgM antibody that binds specifically to the lipid A domain of

endotoxin (HA-1A) has been produced, alleviating

the need to further pursue the active factor in the J5

antiserum.203 In a study of 197 patients with documented Gram-negative bacteremia, treatment with

HA-1A resulted in a lower mortality in 32 of 105

patients (30%), compared with 45 of 92 patients

(49%) in the control group. A similar benefit was

seen in those patients who were admitted to the

hospital with a diagnosis of Gram-negative

bacteremia and shock (33% mortality with treatment, compared with 57% in the control group).

Although mortality was lowered as a whole for

patients who received the antibody, the 63% of

study patients who did not have documented

Gram-negative bacteremia showed no significant

improvement in survival with the treatment.

Despite the apparent improvement that occurred

in the group of treated patients in this study, a

significant number of the patients with sepsis died,

including approximately one third of patients with

demonstrated Gram-negative bacteremia. The final common pathway in the septic process is the

release of cytokines from macrophages in response

to infections. These compounds may be the source

of many of the adverse effects seen in those patients

in this study with documented Gram-negative

bacteremia who died, as well as in that group of

patients who had sepsis/SIRS but did not have a

Gram-negative infection. If the septic process has
Anesthesia and Perioperative Care of the Combat Casualty

642

progressed beyond the endotoxin interaction with

macrophages, or if it is caused by a non-Gramnegative organism, treatment with the HA-1A antibody would not be expected to cause significant

improvement.

Immunological or pharmacological modulation

of the cytokine release may be of additional benefit

in patients with sepsis. Antibodies directed at TNF

have proven beneficial in animal studies and are

now beginning to be investigated in human studies.

Antagonists against platelet activating factor and

the use of pentoxifylline against TNF and IL-1 are

also being studied.191,198

Hence, immunotherapy directed at different steps

in the septic process is being developed. Combination therapy with antibiotics, other pharmacological agents, and immunomodulation of sequential

stages of sepsis is being investigated intensively

and may prove to be the most effective. This combined approach may be beneficial because the stage

in the sepsis continuum in which a given patient lies

is not easily determined.198

Immunoglobulins cannot, however, be administered with impunity. An upper limit may exist

beyond which host-defense mechanisms, such as

decreased production of immunoglobulin, are impaired.204 One researcher states this concern regarding immunotherapy:

A word of caution is warranted regarding the use of

inhibitors of the mediators of septic shock. The

pathogenetic mechanisms of septic shock are complex and interdependent, and many of them represent the body’s compensatory response to sepsis

and therefore have salutary effects.32(p1476)

Also of practical concern is the enormous costs

involved in immunotherapy.198 Nevertheless, the

promise of an effective management tool against

sepsis makes this form of therapy worth ongoing

evaluation.

Corticosteroids

The use of glucocorticoids in sepsis/SIRS has

been theorized to be beneficial by preventing

the release of mediators of tissue damage and hemodynamic instability, improving cardiac performance, inhibiting inflammation and complement

activation, stabilizing cell membranes, and preventing lysosomal release.191 Impaired immune responses such as leukocyte chemotaxis that occurs

with their use may, however, be harmful. Animal

studies done in 1976 suggested some benefit, although usually only when administered before or

soon after experimentally induced sepsis. In 1976,

a prospective, randomized, controlled study205 of

patients with sepsis who were treated with infusions of high-dose glucocorticoids reported a reduction in mortality with treatment (10% vs 38%).

The results of this study have not been replicated,

but have prompted several evaluations of the possible role of glucocorticoids in both sepsis and septic shock as well as in the treatment and prevention

of ARDS.

Studies of Adult Respiratory Distress Syndrome

At least two studies have failed to demonstrate a

significant benefit when corticosteroids were used

in the management of ARDS. In one study206 of 99

patients with established ARDS from several causes,

treatment with methylprednisolone (30 mg per kg

body weight given every 6 h for 24 h) was evaluated. The study reported no difference in mortality

or in the reversal of ARDS with treatment. A similar

study207 of patients admitted to an ICU with fever

and hypotension, using methylprednisolone in an

identical fashion, failed to demonstrate any reduction in the subsequent development of ARDS or of

mortality. One recent uncontrolled study208 of patients with established ARDS reported that a sustained course of steroids resulted in improvement

of ARDS; however, these results have yet to be

verified in a controlled fashion.

Studies of Human Sepsis

Other studies have attempted to confirm the previously reported benefits of steroids in the treatment of sepsis. In one study209 investigating the

effects of high-dose corticosteroids in patients with

septic shock, patients were treated an average of 18

hours after the onset of sepsis with methylprednisolone (30 mg/kg), dexamethasone (6 mg/kg), or

no therapy. A one-time second dose was administered 4 hours later if shock persisted. Patients who

received steroids within 4 hours after the onset of

shock had a higher incidence of shock reversal.

Similarly at 24 hours after drug administration,

more patients who received treatment had reversal

of shock than those who did not. However, over the

course of the study, the reversal of shock disappeared and no improvement in survival was apparent. These researchers concluded that steroids were

not beneficial, although they may be helpful early

in the septic course in a select group of patients.

Two other controlled studies that followed

reached similar conclusions. In 1987, the Veterans
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

643

Administration Systemic Sepsis Cooperative

Group210 reported a study of patients with sepsis

who received a high-dose corticosteroid bolus (30

mg/kg methylprednisolone) followed by an infusion (5 mg/kg/h for 9 h) within an average of 2.8

hours after the diagnosis of sepsis had been made.

Again, no statistical improvement in survival was

noted at 14 days. Also in 1987, another group211

published the results of their controlled multicenter

study, in which patients received 30 mg/kg of methylprednisolone every 6 hours for four doses beginning within 2 hours of the diagnosis of sepsis or

septic shock. They found no significant improvement in the treatment group with regard to the

prevention of shock, reversal of shock, or overall

mortality; however, the incidence of secondary infections was increased.

So despite the improvement noted in a 1976 animal study,205 the conclusions of more-recent studies

in sepsis are that high-dose corticosteroids have no

place in the management of sepsis. And also, despite the recent, uncontrolled report208 of the use of

a sustained course of corticosteroids in established

ARDS, most controlled data suggest that steroids

neither prevent nor reverse ARDS.

Naloxone

Endogenous opioid peptides have been reported

to be involved in the pathophysiology of septic

shock. Animal studies that utilize the opioid antagonist naloxone have demonstrated some improvement in the treated animals’ conditions.191

Clinical responses in humans have been varied,

however. Most often cited is a 1981 study212 in

which blood pressure increased in 8 of 13 patients

with hypotension and shock following the infusion

of 0.4 to 1.2 mg of naloxone, although only 3 of the

13 treated patients survived. Most of the nonresponders in this study were adrenally insufficient; hence, it has been postulated that naloxone

therapy requires intact adrenocortical function.

Prolonged infusions of naloxone have been shown

to reduce inotropic and vasopressor requirements

and improve stroke volume and heart rate.213 One

uncontrolled study214 reported an increase in systolic and mean arterial pressure in patients with

sepsis with a naloxone bolus followed by an infusion, although no overall effect on mortality was

observed. Naloxone may provide a temporizing

means to improve the hemodynamics or cardiovascular status of a patient in septic shock. But without

a randomized, prospective, controlled study, its use

to improve survival remains unproven.

Cyclooxygenase Inhibitors

Cyclooxygenase inhibitors and thromboxane synthetase inhibitors have also been shown to have

some benefit in animal models of sepsis.191 Many of

the mediators of sepsis activate enzymes that release fatty acids, such as arachidonic acid, from cell

membranes. Cyclooxygenase inhibitors such as

indomethacin may help ameliorate some of the

hypotension and organ damage reported to be associated with arachidonic acid metabolites. Administration of ibuprofen decreases extravascular lung

water in septic animals.58

Metabolic Manipulations

Bacterial translocation from the bowel has been

discussed as a potential endogenous source of enteric, Gram-negative sepsis. Total parenteral nutrition and the absence of enteral feeding have been

associated with gut mucosal atrophy, bacterial and

fungal invasion, and increased mortality.191 As

demonstrated in animal models, bacterial translocation from the gut is increased in animals fed

parenterally versus those receiving enteral feeding.215 Early enteral feeding stimulates gut function

and protects the gut barrier. The early institution of

enteral feeding may prove to be a major therapeutic

modality in the prevention of sepsis. This was the

case in trauma victims who had fewer infections

and lower mortality when fed enterally.216

Calcium abnormalities are common in the septic

state. The hypocalcemia seen appears to result from

aberrations in the parathyroid hormone–vitamin D

axis, perhaps aggravated by endotoxin.217 Although

hypocalcemia is usually mild, it can be severe. Only

ionized calcium levels can accurately reflect true

hypocalcemia. Replacement, though, is not always

indicated, for intracellular calcium overload results

in activation of protease and other digestive enzymes and the uncoupling of oxidative phosphorylation, with the end result being cellular death.218

Sepsis itself may increase intracellular calcium by

diminishing adenosine 5’-triphosphate (ATP), by

interfering with calcium transport systems, or increasing calcium entry into the cell, or both.191 In

this regard, the calcium channel–blocking agents

have been shown to improve hemodynamics, cardiovascular function, and survival in a dog model

of sepsis.219 Further study is warranted before widespread use of calcium channel–blocking agents in

sepsis is recommended.

Other investigational therapies for sepsis are also

being explored.191 Toxic oxygen radicals have been
Anesthesia and Perioperative Care of the Combat Casualty

644

implicated in many clinical disorders including

sepsis/SIRS. Enzymes such as superoxide

dismutase, catalase, and peroxidase are being evaluated for their ability to remove free radicals. Xanthine oxidase, which is involved in free-radical formation, is inhibited by allopurinol; iron chelators

such as desferrioxamine limit the availability of

iron and therefore also limit the subsequent freeradical formation. Many other theoretical modes of

therapy are being investigated. Most of these require more animal testing before clinical trials can

be initiated. As is the case with the corticosteroids,

widespread acceptance or rejection of a new therapy

requires proven clinical efficacy through a welldesigned, randomized, controlled, and preferably

double-blind study.

ESTABLISHED MULTIPLE ORGAN FAILURE

Multiple, sequential, progressive organ failure

as a syndrome is relatively newly described. Other

nomenclature used in the literature of the past include the syndromes of hypermetabolism220 and

malignant intravascular inflammation.221 The initial descriptions of an organ-failure syndrome were

written near the end of the Vietnam War.4,5 Since

then, the United States has been involved in no

major conflict or war resulting in a large number of

casualties, and most of the military medical experience in recognizing and treating the syndrome results from the peacetime care of military members,

their dependents, and retirees.

Sequential or progressive organ failure following an initial injury or illness was described in

1973.222 The syndrome was defined in 1975.52 In 1980,

Fry and associates223 reported the principal predisposing factors for the development of MODS: (a) resuscitation with a large volume of fluid or (b) the presence

of infection. This paper was also the first to report

the mortality rate for multiple, sequential organ failure. The development of multiple organ failure became an accepted indication for an exploratory

laparotomy to search for an unrecognized source of

sepsis. Also in 1980, infection was observed to be

not the only preceding factor for the development

of multiple organ failure, as only 50% of patients

were found to have positive blood cultures.224 The

term “non-bacteremic sepsis” was coined to describe this phenomenon. By 1985, other researchers225 wrote that multiple organ failure could

be produced by any process initiating an inflammatory response.

Multiple organ failure is now the major cause of

death in patients surviving longer than 48 hours

following severe trauma, and is also the most common cause of death in patients in surgical ICUs.220

Before we can discuss the importance or prevalence of this medical condition, we must clearly

define the syndrome. Much of the earlier research

regarding this condition was hampered by the lack

of a uniform description or definition. Again, Fry

and associates223 were the first to carefully define

organ-system dysfunction in the postoperative patient. The frequency of multiple-system organ failure was retrospectively examined in 1,200 patients.

The criteria used for sepsis were the most strict;

thus, these patients were quite seriously ill.

In 1985, using a large database, the Critical Care

Medicine group at George Washington University

Hospital, Washington, D. C., developed a uniform

set of definitions of organ system failure (Exhibit

24-6).91 Their goal—to use criteria that were not

only objective but also independent of therapy—

was intended to facilitate an analysis of patient

therapy and outcome. The definition for respiratory failure was the exception to these stringent

criteria; respiratory failure is increasingly difficult

to define when the clinical signs are masked by

mechanical ventilatory support.

Prevalence

The George Washington University team used

the definitions in Exhibit 24-6 to evaluate more than

2,800 patients admitted to ICUs in 13 medical centers within the United States and more than 2,400

patients admitted to ICUs in hospitals in France.

The resultant combined database contained 5,248

randomly selected admissions to ICUs. The prevalence of organ-system failure on admission was not

published in the 1985 study, but, “49% [of the patients met] at least one of the definitions prior to

discharge from the ICU or death.”226(p224) Furthermore, if multiple organ failure is literally the presence of more than one failed organ system, then this

occurred in approximately 15%, or one of every

seven patients. Three principal factors that would

aid in predicting subsequent development of multiple-system organ failure in patients cared for in

combined medical–surgical ICUs were identified226:

• the severity-of-disease score (as measured

by the Apache II test),

• the admission diagnosis, and

• age greater than 65 years.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

645

Cardiovascular Failure1

Heart rate < 54/min

Mean blood pressure < 49 mm Hg

Ventricular tachycardia or fibrillation

Serum pH < 7.24 with a PaCO2 of < 49 mm Hg

Respiratory Failure1

Respiratory rate < 5/min or > 49/min

PaCO2 > 50 mm Hg

A–aDO2 > 350 mm Hg, with A–aDO2 calculated as

(713 • FIO2) – PaCO2 – PaO2

Dependent on ventilator on the 4th d of organ

system failure

Renal Failure1

Urinary output < 480 mL/24 h or < 20 mL/h/8 h

Serum blood urea nitrogen > 100 mg/dL

Serum creatinine > 3.5 mg/dL

EXHIBIT 24-6

DEFINITIONS OF ORGAN SYSTEM FAILURE

One of the following criteria needs to be met during a 24-hour period:

Hematological Failure1

White blood cells < 1,000 mm3

Platelets < 20,000 mm3

Hematocrit < 0.20

Neurological Failure1

Glasgow coma score < 6 in the absence of

sedative drugs

Hepatic Failure2

The patient must have both:

Bilirubin > 6 mg/dL

Prothrombin time > 4 s over control, in the

absence of systemic coagulation defect or

anticoagulant medication

A–aDO2: alveolar – arterial difference in partial pressure of oxygen; FIO2: fraction of inspired oxygen; PaCO2: arterial partial

pressure of carbon dioxide; PaO2: arterial partial pressure of oxygen

Data sources: (1) Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Prognosis in acute organ-system failure. Ann Surg.

1985;202:685–693. (2) Knaus WA, Wagner DP. Multiple systems organ failure: Epidemiology and prognosis. Crit Care Clin.

1989;5(2):221–232.

Additional authorities have reported the subsequent development of multiple organ failure in

surgical patients (Table 24-6).

Prognosis

Several researchers have investigated the risk of

death from MODS (Tables 24-7 and 24-8).91,223,227,228

Their data demonstrate two main points regarding

the prognosis following the onset of organ failure.

First, patient age greater than 65 years increases the

risk of death by 10% to 20%. The outcome for

elderly patients is also affected to a greater degree

by the length of time during which organ failure

continued. Second, the mortality rate is so high for

patients with three or more organ-system failures

that youthful age is no longer a protective factor. By

the second day of failure of three or more organ

systems, the mortality rate exceeds 90%.

It appears that not all organ-system failures affect mortality equally. In particular, neurological

Data sources: (1) Knaus WA, Draper EA, Wagner DP,

Zimmerman JE. Prognosis in acute organ-system failure. Ann

Surg. 1985;202:685–693. (2) Fry DE. Multiple system organ failure. Surg Clin N Am. 1988;68(10):107–122. (3) Carrico CJ, Meakins

JL, Marshall JC, Fry D, Maier RV. Multiple-organ-failure syndrome. Arch Surg. 1986;121:196–208.

TABLE 24-6

INCIDENCE OF MULTIPLE SYSTEM ORGAN

FAILURE

Prevalance

Date Patient Characteristic (%)

1985 Medical/surgical intensive care unit1 15

1986 Multiple trauma2 5–12

1986 Emergency surgery3 7–22

1986 Intraabdominal abscess3 30–50

1988 Emergency surgery2 7
Anesthesia and Perioperative Care of the Combat Casualty

646

TABLE 24-7

PROGNOSIS FOLLOWING THE ONSET OF MULTIPLE ORGAN FAILURE

ARDS alone (n = 13)1 31

ARDS with MOF (n = 38)1 74

ARDS with MOF2 50

Patient Characteristics Mortality (%) Patient Characteristics Mortality (%)

Emergency surgery/MOF3 74

Medical-surgical ICU/MOF admissions4 64–98

ARDS: adult respiratory distress syndrome

ICU: intensive care unit

MOF: multiple organ failure (> two organ failures)

Data sources: (1) Richardson JD. Adult respiratory distress syndrome. Surg Profiles. 1988;10–15. (2) Bell R, Coalsu J, Smith J. Multiple

organ system failure and infection and the adult respiratory distress syndrome. Ann Intern Med. 1983;99:293–298. (3) Fry DE,

Pearlstein L, Fulton RL, Polk HC. Multiple system organ failure. Arch Surg. 1980;115:136–140. (4) Knaus WA, Draper EA, Wagner

DP, Zimmerman JE. Prognosis in acute organ-system failure. Ann Surg. 1985;202:685–693.

TABLE 24-8

AGE-RELATED RISK OF DEATH FROM MULTIPLE SYSTEM ORGAN FAILURE

Day of No. of Failed 64 Years Old and Younger 65 Years Old and Older All Ages

Failure Organ Systems Deaths Patients % Deaths Patients % Deaths Patients %

1 1 440 2,297 19 488 1,323 37

2 313 718 44 267 419 64

3 or more 404 491 82

2 1 294 1,291 23 347 842 41

2 262 561 47 221 302 73

3 or more 302 322 94

3 1 248 1,036 24 309 672 46

2 219 415 53 153 214 71

3 or more 208 223 93

4 1 221 846 26 264 561 47

2 185 350 53 139 191 73

3 or more 152 159 95

5 1 198 729 27 235 491 48

2 160 311 51 128 178 72

3 or more 127 131 97

6 1 170 615 28 222 441 50

2 146 270 54 111 138 80

3 or more 103 105 98

7 1 145 542 27 179 353 51

2 126 217 58 87 105 83

3 or more 103 105 98

Adapted with permission from Knaus WA, Wagner DP. Multiple systems organ failure: Epidemiology and prognosis. Crit Care Clin.

1989;5(2):228.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

647

They believed that these bacteremic episodes were

the result of bacteria translocated across the gastrointestinal tract. In order for this event to occur, the

authors postulated that there must be a break in the

gastrointestinal tract mucosal barrier, which is followed by either perihepatic shunting or an overwhelming of the hepatic reticuloendothelial system, as previously demonstrated in states of

starvation, excessive alcohol use, or use of corticosteroids. Many studies have been published since

that support the translocation of bacteria across the

gastrointestinal lumen (Table 24-9).

In 1985, the interaction of endotoxin (also called

lipopolysaccharide) with hepatic Kupffer cells was

reported in an animal model.230 The result was a

marked decrease in hepatic protein synthesis and

subsequent liver failure. Endotoxin that was administered systemically did not have the same effect. Much of the adverse effects appeared to be

mediated through the macrophage (Kupffer cell),

and its secretory products including complement,

IL-1, the prostaglandins, and oxygen free radicals.

The report suggests that

[because lipopolysaccharide] is known to activate

Kupffer cells and other macrophages, and [lipopolysaccharide] had no effect on isolated hepatocytes, all combine to support the idea that endotoxin may stimulate Kupffer cells to release

mediators, which impair hepatocyte function.230(p93)

Thus, new information revealed that bacteria alone

may not be responsible for all of the effects on organ

systems, and that the presence of live bacteria are

not necessary to initiate the cascade. This observation further supports the existence of “culture-negative” sepsis.

In 1985, a retrospective review225 comparing patient groups of multiple trauma to those with intraabdominal infections and sepsis was published.

The incidence of patients with a blood culture positive for bacteria was 40% in the trauma group compared with 73% in patients with intraabdominal

sepsis. However, the sequence and severity of

organ failure were the same in both groups. Pulmonary failure occurred within 3 days, followed by

hepatic, and finally, cardiovascular. Of patients

with MODS, 34% had negative blood cultures. The

theoretical pathophysiological explanation is that

complement is activated, which stimulates polymorphonuclear cells to aggregate, which, in turn,

releases prostaglandins and oxygen free radicals,

setting in motion a vicious circle:

failure has been associated with an independent

mortality rate of nearly 40%. All other organ-system failures are accompanied by approximately a

30% risk of death. However, the researchers at

George Washington University Hospital concluded

in 1989:

Indeed it can be argued that virtually all patients

who die in intensive care units, unless they have

sudden death, die with some degree of multiple

system organ failure.226(p224)

Etiology and Pathophysiology

A brief review of the medical literature published only during the 1980s will help the reader

understand the pathophysiology of this condition.

(In view of the still-evolving descriptions of this

syndrome and our incomplete understanding of it,

hereinafter we will use the term MODS when discussing this syndrome in its historical context, regardless of the extant terminology.) During 1980,

MODS was believed to be the result of either an

inadequate circulatory state or unresolved sepsis.

Fry’s research revealed four pathological conditions, each of which was associated with a 24% to

28% incidence of MODS: (1) oligemic shock, (2)

septicemia, (3) massive crystalloid therapy (> 6 L)

and (4) massive blood therapy(> 6 units).223 The

latter two conditions were associated with the development of MODS independent of the initial disease state.

In further support of the role of infection during

this syndrome, Fry demonstrated that 34 of 38 (89%)

emergency surgery patients with two or more organ-system failures had sepsis. Furthermore, 100%

of patients with three or more organ-system failures had sepsis, and infection was considered to be

the cause of death in 58% of all fatalities.223

Fry believed that abnormal oxygen utilization

secondary to infection was common and in 1980

supported that view with the following observation:

The failure of organ function in tissues anatomically and functionally different suggests that a common cellular insult may be the fundamental

pathophysiologic event in patients with uncontrolled systemic infection.223(p139)

By 1982, while reviewing enterococcal bacteremia,

Garrison and Fry229 reported that 48 of 114 patients

(42%) had no identifiable primary focus of infection

and did not respond to the usual antibiotic regimen.
Anesthesia and Perioperative Care of the Combat Casualty

648

bal circulatory injury.”231(p888) While established

MODS is nearly always manifested by hepatic failure, one study reveals two separate clinical courses

for the development of this condition220:

• One subset of patients has lung injury as

the predominant clinical feature with other

organ failure developing shortly before

death.

• A second, more-common clinical course is

early lung injury followed by a stable period of 10 to 14 days, after which progressive organ failure occurs.

Metabolic Changes

In addition to a greatly increased metabolic rate

and oxygen requirement, the body’s handling of

cellular substrate changes. The metabolic mechanism that normally promotes the entry of pyruvate

into the Krebs cycle decreases. Despite the fact that

glucose cannot be utilized properly, a relative insulin deficiency exists, which results in hyperglycemia

as a result of increased glucagon, increased hepatic

gluconeogenesis, and increased glycolysis. Increased

lactate production is an additional result of the changed

metabolism of pyruvate. The body’s tissues must

[I]t should be realized that after appropriate surgery the vicious circle of activated complement,

permeability edema, and tissue anoxia is in itself

able to perpetuate severe generalized inflammation

and has the potential to kill the patient.225(pp1114–1115)

Clinical Manifestations

One of the features that distinguishes MODS is

the usual sequential failure of organ systems, as

opposed to the immediate failure of many organs

that is seen with trauma. An inciting injury or event

is followed initially by successful resuscitation. This

may be followed by a period of 2 to 3 days of relative

stability. Following this is a period of hypermetabolism (manifested by a near doubling of the patient’s

metabolic rate and carbon dioxide production). The

mortality during this phase alone is approximately

25% to 40%.21 If the patient’s metabolic needs are

not abated by resolution of infection, inflammation,

or circulatory compromise, then progressive organ

failure will develop in approximately 7 to 21 days.

This occurs in approximately 40% of patients who

develop the hypermetabolic state.220

Thus, although the an initiating injury may have

been localized to a single organ (eg, the lung), the

physiological response can be thought of as a “gloTABLE 24-9

EVIDENCE OF BACTERIAL TRANSLOCATION IN THE GASTROINTESTINAL TRACT

Date Model Significant Findings

19691 Human shock Histological changes in the gastrointestinal tract were observed after shock

19742 Animal Candida organisms were found to cross from the gastrointestinal tract to

the portal venous system

19823 Human sepsis Description of focus enterococcal bacteremia

19884 Animal Translocation of bacteria into the mesenteric nodes was proven at

autopsy, yet fewer than one third had positive blood cultures

19885 Animal, nontraumatized and Higher incidence of bacteria in mesenteric lymph nodes was seen in

on total parenteral nutrition the group receiving nothing by mouth

19896 Animal, in hemorrhagic Mesenteric lymph nodes, liver, and blood were all positive for

shock bacteria

Data sources: (1) Sorenson FH, Vetner M. Hemorrhagic mucosal necrosis of the gastrointestinal tract without vascular occlusion. Acta

Chir Scan. 1969;135:439–448. (2) Stone HH, Kolb LD, Currie CA. Candida sepsis: Pathogenesis and principles of treatment. Ann Surg.

1974;179:697–711. (3) Garrison RN, Fry DE. Enterococcal bacteremial clinical implications and determinants of death. Ann Surg.

1982;196:43–47. (4) Baker JW, Deitch EA, Berg RD, Specian RD. Hemorrhagic shock induces bacterial translocation from the gut. J

Trauma. 1988;28(7):896–906. (5) Alverdy JC, Aoys E, Moss GS. Total parenteral nutrition promotes bacterial translocation from the

gut. Surgery. 1988;104:185–190. (6) Deitch EA, Bridges W, Ma L, Berg R, Specian RD, Granger DN. Hemorrhagic shock-induced

bacterial translocation: The role of neutrophils and hydroxy radicals. J Trauma. 1990;30(8):942–951.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

649

receive their substrate needs from other sources

(eg, fat and protein). This results in increased

lipolysis and decreased peripheral lipoprotein lipase activity, and leads to hypertriglyceridemia.

Administration of excess lipid via nutrients can

lead to hypoxemia and immunosuppression.220

Perhaps the most injurious metabolic feature of

this syndrome is the extreme catabolism resulting

from muscle breakdown: urinary nitrogen excretion exceeds 20 g/d.220 A marked decrease in the

normal hepatic synthesis of albumin and other proteins compounds this protein loss.

Pulmonary Failure

The lung is usually the first organ to fail in the

sequence of MODS.223 Pulmonary injury may occur

directly (eg, via aspiration or infectious pneumonia) or secondarily (eg, via sepsis). Why does the

lung so frequently become injured in patients who

have distant foci of infection or injury? The answer

probably can be found in two pathophysiological

mechanisms:

1. Inflammatory mediators and toxic byproducts are released.

2. Cellular aggregates comprising leukocytes,

platelets, and fibrin may block pulmonary

capillaries leading to an elevation of the

pulmonary vascular resistance and ventilation–perfusion abnormalities. (This

mechanism is inherent to the normal function of the lung as a component of the

reticuloendothelial system.)

Patients in an early state of MODS may present

with “soft” clinical signs and symptoms of distress

(ie, a slight increase in respiratory rate and a subjective feeling of dyspnea at rest). This frequently

progresses rapidly to respiratory failure accompanied by marked tachypnea, the use of accessory

muscles of respiration, and hypoxemia. Patients in

early MODS require mechanical ventilatory support for hypoxemia, which requires that supplemental oxygen be administered to an elevated concentration, and to provide relief from the work of

breathing. In models of respiratory failure, blood

flow to the diaphragmatic musculature alone may

use up to 30% to 40% of the entire cardiac output.232

The pathophysiological changes include decreases

in both (a) pulmonary compliance associated with

interstitial fluid accumulation and (b) the functional

residual capacity (ie, the volume that ensures normal oxygenation of the continuous blood flow adjacent to the alveoli). Positive end-expiratory pressure functions mainly to increase this volume, which,

in turn, generally decreases the shunted fraction.

Despite the problem that hypoxemia presents,

these patients generally do not die of hypoxia.

Maintaining a PO2 greater than 60 mm Hg is usually

not difficult. The clinical situation is more complicated; PO2 represents only the dissolved oxygen

carried in the blood. In ARDS and MODS, it appears that some tissue beds do not utilize oxygen.

Much of the current literature supports the contention that this is caused by the shunting of blood flow

past tissue or organ beds, particularly in the splanchnic circulation.150,233

Once mechanical ventilatory support is required,

additional risks include a significant incidence of

nosocomial pneumonia, oxygen toxicity, and a state

of lung inflammation that acts as a self-perpetuating cause of further organ damage.

The lung also functions as a metabolic organ,

clearing vasoactive substances such as the

prostanoids and bradykinin from the circulation.

When this lung function fails, elevated plasma levels of certain mediator substances may also play a

role in the hemodynamics of sepsis, manifesting as

refractory vasodilation.

Cardiovascular Failure

The hemodynamic responses are the best-studied clinical signs in patients with either sepsis/SIRS

or MODS. Most clinicians are aware that high

cardiac output and low systemic vascular resistance measurements are characteristic. However,

not all patients who demonstrate these values, as

measured by the pulmonary artery catheter, should

be labeled septic, for the following reasons:

1. Systemic vascular resistance is a calculated

variable, so if an elevated cardiac output

occurs, the systemic vascular resistance

value will be calculated as low. This may

not match the patient’s actual physical

state.

2. High cardiac output and decreased systemic vascular resistance have other causes,

including severe anemia, cirrhosis, excessive volume resuscitation, thryotoxicosis,

and arteriovenous malformation or shunt.

Despite the consistent measurements of high cardiac output, there is still considerable myocardial
Anesthesia and Perioperative Care of the Combat Casualty

650

dysfunction observed in sepsis or MODS.77 Myocardial depression, as evidenced by a global

cardiomyopathy or dilation of the left ventricle, has

been documented. Patients who are unable to develop this dilation, usually viewed as an abnormal

state, have a higher mortality than patients who do.

In patients with ARDS, improved survival has been

observed to be associated with an elevated left ventricular end diastolic volume. This compensatory

response allows for the development of an increased

stroke volume, cardiac index, and oxygen delivery.

Increasing evidence has demonstrated dysfunction

of the right ventricle as well, particularly if there are

high pulmonary arterial pressures.82,83

The most obvious hemodynamic change is the

profound degree of vasodilation, which results in

hypotension. This low perfusion pressure at the

time of increased metabolic needs may further contribute to organ damage. Despite a high cardiac

output, blood flow does not appear to be properly

distributed among tissues, leading to an inappropriately high, mixed venous-oxygen content, reflecting a decreased tissue-organ oxygen uptake.234

The degree of oxygen debt may reflect the elevated arterial lactate level and is correlated with

decreased survival.235,236 A low cardiac output is

observed only in the final stages of sepsis or MODS,

with this caveat: some patients with a previous

history of myocardial infarction, particularly the

elderly, are unable to mount a hyperdynamic response. This compensatory response—hyperdynamic circulation—appears to increase the probability of survival.160

Other possible explanations for an abnormal relationship between oxygen delivery and consumption include the following:

• The tissues may not be able to extract oxygen.

• There may be areas of underperfused capillary beds (unrecruited).

• A disproportionate percentage of the cardiac output may be delivered to organs

with low metabolic demands and oxygen

extraction (eg, skin and muscle).

• Arteriovenous shunts may occur in the

precapillary tissue beds.

• Endothelial injury may result in tissue

edema, thereby increasing the distance

across which oxygen must diffuse.

• Microthrombi may block the peripheral

vascular bed.

• Mediator-induced vasoconstriction may

reduce flow through tissue vascular beds.

Hepatic and Gastrointestinal Failure

The liver and other components of the gastrointestinal tract comprise another organ system that fails

in MODS. This organ system’s role in the pathophysiology and clinical features of MODS was ignored for many years, but interest has been renewed. Some authorities view the gastrointestinal

tract as a target organ, while others see it as the

motor that drives the entire MODS process.220,237,238

Primary among the clinical signs seen are those

involving hepatic injury. The liver is directly downstream from the gastrointestinal tract, and thus may

be exposed to a large number of bacteria translocated into the portal venous system.239 Functioning

as a component of the reticuloendothelial system,

the liver filters out bacteria and particulate matter.

Hepatic Kupffer cells comprise nearly 70% of the

body’s entire macrophage population.

The gastrointestinal tract appears to play a significant role in the perpetuation of MODS, usually

manifesting injury concomitantly with the lungs:

[T]he important role played by the reticuloendothelial system is suggested by the fact that the liver

and lungs, two large reticuloendothelial organs,

are in series and can, therefore, filter particulate

matter from blood draining from the [gastrointestinal] tract, preventing their passage to the systemic

circulation.240(p199)

Thus the liver may become injured, mechanically

blocked, or it may completely fail.241 The clinical

signs are jaundice, altered protein handling, and

immunosuppression from a decreased secretion of

IgA antibodies.

The stomach is also known to be affected in these

syndromes. Endotoxin decreases mucosal blood

flow, increases mucosal permeability, and increases

total acid production.242 The result may be stress

ulceration or gastritis and gastrointestinal hemorrhage. This is much less frequent than it was even

as recently as the 1980s, as antacids, histamine blocking agents, or sucralfate (Carafate, manufactured

by Marion Merrell Dow, Kansas City, Mo.) are now

routinely administered to seriously ill patients. This

may come with a price, though, as bacterial overgrowth in the stomach occurs when the normal

acidic environment is changed to alkaline. The

same bacteria were found in the stomach and upper

airway in 52 of 60 (87%) surgical ICU patients.243

Small-bowel dysfunction frequently occurs, presenting as abdominal distention, ileus, or intolerance to enteral feeding.240 This occurs secondary to

edema of the small-bowel wall and a decrease of the
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

651

villous absorptive area. Animal models of shock

show that these changes may occur within hours of

the inciting injury.191

The gallbladder is not infrequently involved, with

a pattern of cholecystitis different than usual. Patients who are critically ill as a result of trauma,

burn injury, or medical illness may not tolerate

enteral feeding. The lack of enteral nutrition or the

use of total parenteral nutrition has been associated

with acalculus cholecystitis. The importance of this

condition is the high incidence of gallbladder gangrene (approximately 50%), and perforation (10%).244

Thus, despite their degree of illness, these patients

must have drainage. Recent practice has been to

drain these abscesses percutaneously at the bedside

under ultrasound guidance, rather than to perform

an open cholecystotomy in the operating room.

Renal Failure

Renal failure occurs frequently as a component

of MODS (45%–65% incidence).225 Anecdotally, the

kidneys appear to be injured more from uncontrolled sepsis than they are from the use of relatively toxic antibiotics (eg, gentamicin or tobramycin). Renal failure is discussed as a consequence

of sepsis earlier in this chapter, and is the subject of

Chapter 26, Acute Renal Failure; therefore, it will

not be discussed further here.

Coagulation Failure

The most controversial issue regarding DIC is

the therapy for it. Clearly, the most effective management tool is effective treatment of the underlying or precipitating infection or disorder and associated factors such as shock. The use of heparin in

an attempt to block enhanced clotting activity has

not proven to be efficacious in treating DIC that is

associated with sepsis/SIRS.118 Heparin should be

reserved for use in patients exhibiting thrombotic

complications.122 Replacement therapy with platelets

and fibrinogen is likewise controversial but may be

prudent in the patient who is hemorrhaging.96

Antifibrinolytic agents such as ε-aminocaproic acid

are probably contraindicated due to an increased

incidence of significant thrombotic events.118

Current Treatment Modalities

The current treatment of MODS centers around

four modalities. First and foremost is the prevention, control, or elimination of any known inciting

or promoting condition. This includes the drainage

of abscesses, excision of a burn wound, control of

hemorrhage, and aggressive hemodynamic support

during shock.

The second approach is additional circulatory

resuscitation, the proper end point of which has not

yet been elucidated. The parameters that have been

considered normal are not normal for the critically

ill patient with sepsis.245,246 Previously, conventional wisdom had recommended increasing the

patient’s hemodynamic state only if it fell below

the individual’s baseline preoperative value. More

recently, researchers have recommended increasing oxygen delivery until a supranormal level has

been reached, or until the consumption no longer

increases and the arterial lactate level decreases.160,244,247,248 General criteria to ensure optimal

tissue perfusion include the following:

• minimal or absent acidosis and an arterial

lactate level less than 2 mmol/L, and

• urinary output maintained above 0.5 mL/

kg/h (polyuria may sometimes occur in

sepsis as a result of a concentration defect).

In states of oxygen-supply dependency, use

Shoemaker’s therapeutic goals:

• cardiac index > 4.5 L/min/m2,

• oxygen delivery > 650 mL/min/m2, and

• oxygen consumption > 160 to 170 mL/

min/m2.

An alteration in cardiac function and ventricular

dilation results in right atrial pressure and PCWP,

which do not accurately reflect the intracardiac

volumes. This has been recently confirmed in patients with ARDS.248 The PCWP may help in guiding fluid therapy to avoid further increases in the

extravascular lung water and subsequent pulmonary edema.

The third modality in therapeutic support for

MODS is nutritional or metabolic modification. The

subject, particularly as it applies to combat casualties, is well described in Chapter 23, Metabolic

Derangements and Nutritional Support, and therefore will be mentioned only briefly here. As previously discussed, these patients become markedly

catabolic. Malnutrition results in a decreased function of both humoral and cellular immunity. Specifically, achieving a positive nitrogen balance appears to improve survival. Nutritional formulae

with higher concentrations of the branched-chain

amino acids appear to better increase hepatic synthesis of protein and result in lower urea produc-
Anesthesia and Perioperative Care of the Combat Casualty

652

tion. However, use of high-branched-chain amino

acid formulae does not appear to lessen mortality.246 Most authorities recommend between 1.5 and

2.0 grams of protein per kilogram of body weight

per day. The total caloric supplement should not

exceed 30 to 35 nonprotein kilocalories per kilogram of body weight per day to avoid the development of fatty liver. The calorie-to-nitrogen ratio

should be low, as near 100 as possible.220

A controversy has arisen recently regarding

whether enteral nutrition is superior to parenteral

nutrition for critically ill patients. A prospective

randomized trial248 of enteral versus parenteral nutrition, beginning within 6 days after the onset of

sepsis, demonstrated no difference in the overall

incidence of MODS or mortality. A retrospective

study249 published in 1987 found that patients given

total parenteral nutrition developed higher septicseverity scores than patients fed enterally.

In a prospective study250 done in 1988 that evaluated early enteral feeding following laparotomy for

trauma, patients who received enteral feeding within

12 to 18 hours of admission to the ICU had fewer

infections and improved survival. Animal models

of Escherichia coli peritonitis251 or hemorrhagic

shock252 have demonstrated a marked decrease in

the mortality in groups fed enterally. Specifically,

the peptide-based diets, compared with total

parenteral nutrition for metabolic support, led to

increased survival. Other nutritional therapies are

also being studied:

• Tailored nutritional therapy, including the

administration of fish oil high in omega 3

polyunsaturated fatty acids. These fatty

acids are incorporated into cellular membranes and competitively inhibit the

cyclooxygenase and lipoxygenase pathways. This has been shown to decreases the

production of prostaglandins and leukotrienes (such as TNF and IL-1) by hepatic

macrophages.

• Increased glutamine diet. Glutamine is a

trophic factor and increases the small-bowel

villous absorptive area. Glutamine is also

thought to be involved in maintaining the

mucosal-barrier function of the gastrointestinal tract.

The fourth modality in treating renal failure in

patients with sepsis/SIRS or MODS is hemodialysis.

Because supporting renal failure with hemodialysis

is the subject of Chapter 26, Acute Renal Failure, it

will not be discussed in this chapter.

SUMMARY

Although the etiologies of the syndromes of systemic inflammatory response and multiple organ

dysfunction are varied, the pathophysiological

mechanisms leading to their clinical manifestations

are remarkably similar. The current state of our

understanding reveals this to be the result of the

activation of the patient’s endogenous cellular and

humoral defense systems with the subsequent release, activation, or synergistic stimulation of endogenous mediator substances. The multiplicity of

these mediator-induced cell-to-cell and tissue interactions reveals the extreme complexity of the

human response to foreign material (ie, endotoxin

released from Gram-negative bacteria). Good medical supportive care remains a cornerstone of therapy

for patients with sepsis/SIRS to prevent progression to MODS. Early recognition and aggressive

treatment of (a) persistent foci of infection or inflammation and (b) residual microcirculatory shock

cannot be overemphasized: appropriate treatment

by the vigilant clinician can alter the outcome of

these patients before the abnormalities of these syndromes become irreversible.

The body’s initial, local, tissue response to infection or inflammation is beneficial. If, however, the

response becomes generalized, the body becomes

flooded with a multitude of complex mediators; this

initiates an unrestrained, perpetuating, systemic response. The nature of some of the mediators (ie, the

endotoxin moiety) and the subsequent antigen–antibody formation suggest that immunotherapy might

be useful in obviating the effects. Immunotherapy

may become an effective treatment in the future.

Sepsis/SIRS and MODS have particular relevance

for medical officers. Although the actual number of

soldiers who die of these syndromes is small, the

potential that this population may benefit from

lifesaving intervention is great.
The Syndromes of Systemic Inflammatory Response and Multiple Organ Dysfunction

653

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Acute Respiratory Failure and Ventilatory Management

667

GERALD HARRINGTON, M.D.*; WILLIAM MARX, D.O.†; AND DANIEL P. STOLTZFUS, M.D.‡

Chapter 25

ACUTE RESPIRATORY FAILURE AND

VENTILATORY MANAGEMENT

*Lieutenant Colonel, Medical Corps, U.S. Army; Department of Surgery, Critical Care Service, Brooke Army Medical Center, San Antonio, Texas 78234-6200

†Lieutenant Colonel, Medical Corps, U.S. Army Reserve; formerly, Director, Surgical Critical Care and Staff, General Surgery Service, Fitzsimons Army Medical

Center, Aurora, Colorado 80045-5001; currently, Assistant Professor of Surgery and Critical Care Medicine, Interim Director, Surgical Critical Care, State

University of New York Health Science Center of Syracuse, 750 East Adams Street, Syracuse, New York 13210

‡Formerly, Major, Medical Corps, U.S. Army; Staff Anesthesiologist, Staff Intensivist, Anesthesia and Operative Services, Walter Reed Army Medical Center,

Washington, D. C. 20307-5001; currently, Assistant Professor of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida 32608-1197; Codirector, Surgical Intensive Care Unit, Veterans Affairs Medical Center, P. O. Box 100254, Gainesville, Florida 32610-0254

INTRODUCTION

EPIDEMIOLOGY OF RESPIRATORY FAILURE IN COMBAT CASUALTY CARE

ETIOLOGY OF PULMONARY INSUFFICIENCY

Mechanical Trauma

Thermal Trauma

Chemical Warfare

Nuclear Warfare

INDIRECT MECHANISMS OF RESPIRATORY INSUFFICIENCY

Pulmonary Aspiration

Hydrostatic Pulmonary Edema

Adult Respiratory Distress Syndrome

DIAGNOSING RESPIRATORY FAILURE

Hypoxemia

Ventilatory Failure

Combined Hypoxemia and Ventilatory Failure in Postoperative Casualties

MANAGING RESPIRATORY FAILURE

Supportive Care

Endotracheal Intubation

PHYSIOLOGICAL EFFECTS OF MECHANICAL VENTILATION

Pulmonary Effects

Cardiovascular Effects

Renal Effects

COMPLICATIONS FROM MECHANICAL VENTILATORY SUPPORT

ETHICAL DILEMMAS IN USING LIMITED LIFE-SUSTAINING THERAPY

MECHANICAL VENTILATION AND COMBAT CASUALTIES

Indications for Mechanical Ventilation

Functional Design of Mechanical Ventilators

Modes of Positive-Pressure Ventilation

INITIATING MECHANICAL VENTILATION

Tidal Volume and Respiratory Rate

Fraction of Inspired Oxygen

Inspiratory Flow Rate

Additional Settings

Stabilizing the Patient in Acute Respiratory Failure

MONITORING THE EFFECTIVENESS OF VENTILATION AND OXYGENATION

Oxygen Concentration

Pulse Oximetry

Gas-Exchange Indices

Monitoring Mechanical Ventilation

WEANING FROM MECHANICAL VENTILATION

VENTILATORS AVAILABLE FOR COMBAT CASUALTY CARE

SUMMARY
Anesthesia and Perioperative Care of the Combat Casualty

668

INTRODUCTION

Respiratory insufficiency in combat casualties is

seen in many different guises depending on the

mechanism and the time of appearance (Exhibit 25-1):

• In some casualties, respiratory insufficiency

is an immediate and direct consequence of

physical trauma to the lungs or the chest

wall. An example might be a soldier who is

shot through the chest and sustains a massive

tension pneumothorax that will cause death

within a few minutes unless immediate care

is rendered by a medic or a medical officer.

• In other casualties, respiratory insufficiency

might develop days after direct trauma to

the chest. An example might be a soldier

who sustained a gunshot wound of the

lung and subsequently develops pneumonia and empyema.

• Unfortunately, some casualties may develop respiratory insufficiency that is, in

part, secondary to the therapies given for

an injury in some other part of the body. An

example might be a soldier who develops

pulmonary edema following excessive fluid

overload that occurred during the treatment of massive blood loss resulting from a

traumatic amputation of a leg.

The most common type of respiratory insufficiency

that military anesthesiologists and intensivists (ie,

critical care specialists) are likely to see, however,

occurs within several days to 1 week following an

injury that did not directly involve the lungs or

chest wall: the adult respiratory distress syndrome

(ARDS). This condition is now recognized as an

expression of the systemic inflammatory response

syndrome (SIRS) and is related to sepsis.

This chapter is intended to provide practical help

to the medical officer who is confronted with casualties whose conditions are of varying degrees of

severity, for whom decisions must be made promptly

to avoid further morbidity from cerebral hypoxia or

EXHIBIT 25-1

ETIOLOGY OF RESPIRATORY FAILURE IN COMBAT AND CIVILIAN PATIENTS

Pulmonary aspiration

Foreign-body obstruction of the airway

Soft-tissue obstruction of the airway:

Prolapse of tongue due to unconsciousness

Prolapse due to facial bone fracture

Edema and hematoma formation

Pulmonary injury:

Hemothorax

Pneumothorax

Hemopneumothorax

Lung contusion

Mediastinal emphysema

Rib fractures

Flail chest

Laryngeal fracture (with or without separation)

Tracheobronchial laceration or separation

Acute lung injury secondary to:

Blast overpressure injury

Chemical war gas

Infection

Hypermetabolism

Inhalation of combustion products

Hypoventilation secondary to:

Cervical spinal cord trauma

Cranial trauma

Exposure to nerve agent

Diaphragmatic hernia

Thoracic wall injury

Central nervous system depression from drugs

or hypoxemia

Adapted with permission from Grande CM, Stene JK, Bernhard WN. Airway management: Considerations in the trauma

patient. Crit Care Clin. 1990; 6(1):43.
Acute Respiratory Failure and Ventilatory Management

669

other visceral organ injury. The chapter emphasizes (1) the recognition of respiratory insufficiency

and (2) the provision of mechanical ventilation for

casualties with respiratory insufficiency at medical

treatment facilities from a third-echelon hospital to

a medical center in the continental United States.

EPIDEMIOLOGY OF RESPIRATORY FAILURE IN COMBAT CASUALTY CARE

Combat casualties do not commonly present with

respiratory insufficiency. Data from the Vietnam

War indicate that probably somewhat less than 5%

of those killed in action had injuries primarily to

the respiratory system exclusive of those who

exsanguinated from injuries to the pulmonary

vasculature.1 Respiratory failure at the hospital

level may be more common. The total number who

die of wounds is about 3% to 4% of hospitalized

casualties; it is probably reasonable to assume that

all of these casualties—at some time during their

hospital stay—would require respiratory support.

Data from the Vietnam War indicate that approximately 0.4% of hospitalized casualties died of what

would now be called ARDS.2 Today, many more

casualties would probably receive prophylactic respiratory support to prevent respiratory insufficiency, so it is not unreasonable to infer from these

data that perhaps 10% of all hospitalized combat

casualties are at risk of developing respiratory insufficiency. Furthermore, if nerve agents or enhanced blast munitions were to be used against U.S.

military forces in a future hostile action, a much

higher percentage of the casualty population will

likely need immediate respiratory support. For

planning purposes, the Department of Defense’s

Deployable Medical Systems (DEPMEDS) treatment

files predict that in a major, high-intensity war, 17%

of hospitalized casualties will require ventilatory

support.3

Although the civilian experience depends on the

type of hospital surveyed, probably no more than

several percent of hospitalized patients develop

respiratory insufficiency. This assumes that about

5% of patients who are admitted to civilian hospitals are transferred to the intensive care unit (ICU),

and that of these, one half require respiratory support for more than 24 hours.4

ETIOLOGY OF PULMONARY INSUFFICIENCY

Mechanical Trauma

The battlefield is replete with potential mechanisms for pulmonary injury and the development of

respiratory failure. Militarily relevant sources of

direct mechanical trauma include penetrating, blunt,

and blast injuries to the lungs and the chest wall. In

addition, many soldiers with severe penetrating

injuries to the brain are not killed outright and

require intubation for airway control and mechanical ventilation. The injury to the brain results in

destruction of the respiratory centers; therefore,

ventilatory drive is absent. During the Vietnam

War, this was probably the most common indication for using respiratory support.

Penetrating Injury

Penetrating thoracic injuries may, in turn, cause

secondary conditions that result in respiratory insufficiency. Pneumothorax reduces the ability to

carry out normal gas exchange. The lack of a negative pressure gradient across the lung parenchyma

leads to alveolar collapse and a resulting intrapulmonary shunting of blood. When a sufficient

amount of tissue collapses, arterial hypoxemia ensues. Tension pneumothorax occurs when air enters

the pleural space during inspiration but is unable to

escape during exhalation. The progressive accumulation of air produces a shift of the mediastinal

structures toward the unaffected side of the thorax.

This event worsens gas exchange by compressing the

unaffected lung and reduces venous return to the

heart, resulting in shock. Hemothorax and hemopneumothorax are found in approximately 50% of

casualties with penetrating wounds of the lung.5

 This

fact is not surprising, given the close anatomical proximity of bronchioles and arterioles within the lung

parenchyma. Small fragments that strike the heart

may cause blood to collect within the pericardial

space. The increased pressure within the pericardium restricts the ability of the ventricles to accept

blood (tamponade). Cardiac output and blood pressure progressively decrease as stroke volume is

reduced. If the tamponade is not reversed, cardiovascular collapse and death result.

Blunt Injury

Blunt chest trauma with rib fractures and potential flail chest (ie, multiple rib fractures that result in

segmental chest wall instability) can occur in a
Anesthesia and Perioperative Care of the Combat Casualty

670

variety of battlefield settings. Underlying pulmonary contusion may be a far more important cause

for respiratory failure than the mechanical dysfunction associated with multiple rib fractures.

Blast Injury

Blast injuries from any type of explosion can be

categorized as primary, secondary, and tertiary.

Primary blast injury is due to the direct effect of the

pressure wave on the body, and is not common.

Secondary blast injury occurs when projectiles and

debris from the explosion strike the victim. Finally,

tertiary blast injury, which is the major cause of pure

blast injury, occurs when the individual is physically displaced by the bulk flow of gases away from

the site of the explosion. The displacement leads to

collision with environmental objects and subsequent trauma.6 A more complete discussion of the

medical consequences of blast injury can be found

in The Medical Consequences of Conventional Warfare:

Ballistic, Blast, and Burn Injuries.

7

The pressure wave from an explosion moves

away from the epicenter at supersonic speeds,

whether through air or water. As primary blast

injury is seen predominantly in the gas-containing

organs, the ears, lungs, and gastrointestinal tract

are the most readily affected. The ear is the most

sensitive, with rupture of the tympanic membrane

occurring at pressures above 35 kPa (kilopascals).

While injury to the ear causes pain and long-term

morbidity, pulmonary damage causes the greatest

Fig. 25-1. The probabilities of eardrum rupture and death from a pulmonary blast injury. These are shown as functions

of both the peak pressure above atmospheric pressure (measured in either kilopascals [kPa] or pounds per square inch

[psi]) and the duration of the overpressure (in milliseconds [ms]). For example, a blast wave with a duration of 1 ms

that has an overpressure of 5 psi can be expected to cause rupture of the tympanic membranes in a few people. If the

overpressure reaches 15 psi, one half of the individuals in the exposed population can be expected to have ruptured

tympanic membranes. Much greater pressures are required before pulmonary injury occurs. A blast wave with a

duration of 1 msec and a peak overpressure of 50 psi can be expected to cause pulmonary injury in a few people.

Doubling that pressure is likely to cause a fatal outcome in about one half of the exposed population. The same lethality

is to be expected with a blast wave that lasts 1 s and has a peak overpressure of 12.5 psi. Note that both axes are

logarithmic. Adapted from Bowen T, Bellamy RF, eds. Emergency War Surgery NATO Handbook. 2nd US rev. Washington, DC: US Department of Defense, Government Printing Office; 1988: 76.

5,000

1,000

500

100

10

Peak Pressure (kPa)

0.1 1 10 100 1,000

Positive Phase Duration (ms)

2

10

100

1,000

50% Eardrum Rupture

Threshold Eardrum Rupture

Threshold Lung Injury

50% Lethality

1% Lethality

Peak Pressure (psi)
Acute Respiratory Failure and Ventilatory Management

671

immediate morbidity and mortality (Figure 25-1).

Diffuse pulmonary contusions with a marked increase in lung water lead to ventilation–perfusion

mismatch and arterial hypoxemia. Disruption of

alveoli with the development of alveolar–pulmonary venous communications create the potential

for air emboli, which is the most common cause of

sudden death in such casualties. The gastrointestinal tract may be disrupted in portions where gas

has collected. The colon tends to suffer the most

gastrointestinal blast injuries, which are manifested

by subserosal and intramural hemorrhage. Gastrointestinal blast injury may result in delayed rupture, days after the traumatic event.8

The clinical presentation of each of these injuries

depends on the amount of energy transmitted to the

various tissues in excess of the tissues’ ability to

dissipate the delivered forces. Significant pulmonary and gastrointestinal damage is unlikely to

have occurred in the absence of tympanic membrane rupture. Arterial air emboli from alveolar–

pulmonary venous communications typically

present with signs and symptoms of cerebral dysfunction. However, direct trauma to the skull (secondary or tertiary blast injury) is more likely to be

the cause of altered neurological function. Evidence of primary blast injury of the lung resembles

the diffuse pulmonary contusion seen in blunt chest

trauma. Chest pain with tachypnea, use of accessory respiratory muscles, and hemoptysis are common findings. The protean manifestations of

barotrauma (injury resulting from elevated peak airway pressure) are frequently seen in these patients.

Pulmonary contusion, pneumothorax, pneumomediastinum, subcutaneous emphysema, and pulmonary interstitial emphysema can be confirmed

with a chest X-ray examination after the patient has

been stabilized. Symptoms of blast injury to the

lung may be delayed 24 to 48 hours, making differentiation from other forms of acute respiratory failure difficult.

The principles of management are detailed in

other textbooks. Briefly summarized, the salient

treatment required for improved survival rates of

casualties with thoracic injuries is as follows:

• Remove the bloody secretions from the airway.

• Seal open chest wounds.

• Evacuate blood and air from the pleural

space.

• Treat hypovolemia.

• Remove blood from the pericardial sac.

• Aggressively treat empyema.

Casualties with blast injuries require additional

care. This follows the basic principles of trauma

care, with the following caveats directed toward

potential complications from the blast:

• Excessive volume resuscitation may complicate the pulmonary contusion present in

most of these patients.

• Positive pressure ventilation may increase

the severity of barotrauma and increase the

possibility of air embolism.

• If oxygenation is inadequate with nasal

cannula or mask, continuous positive airway pressure (CPAP) delivered via a tightfitting mask or endotracheal tube may improve oxygenation without worsening

barotrauma.

Thermal Trauma

Although thermal injuries will be encountered

on the battlefield, this mode of injury is uncommon

in conventional land warfare, occurring in fewer

than 10% of all casualties (see Chapter 1, Combat

Trauma Overview, Figure 1-4). Thermal injuries

are, however, much more common in that subpopulation of soldiers who compose the crew of armored

fighting vehicles, and are even more common in

sailors and air personnel. In fact, fire and associated

smoke inhalation are the most common causes of

combat injury on warships.9 Crewed vehicles—

whether ships, tanks, or aircraft—are loaded with

munitions and fuel and pose a constant hazard of

explosions, fire, and thermal injury secondary to

battle damage. Burns to the skin are what we

usually think of when thermal injuries are discussed,

and in fact, circumferential, full-thickness burns of

the thoracic wall may sometimes restrict chest-wall

motion to the degree that ventilation is compromised. Escharotomy may be required to improve

the restrictive defect. However, the more frequent

and more injurious form of thermal injury is damage to the respiratory system caused by inhaling

steam and the gaseous and particulate products of

combustion such as hydrogen chloride and phosgene from plastic, formaldehyde from wood, and

hydrogen cyanide from polyurethane.

Below the level of the vocal cords, thermal injury

from heated air is usually prevented by efficient

upper-airway cooling. Stridor, hoarseness, and difficulty with phonation all suggest the need to evaluate the upper airway. Injury to the hypopharynx may

lead to delayed airway obstruction, making prompt

endotracheal intubation a lifesaving maneuver.
Anesthesia and Perioperative Care of the Combat Casualty

672

These injuries demonstrate a typical acute-lunginjury pattern of increased alveolar-capillary permeability with noncardiac pulmonary edema.

Iatrogenic factors may complicate the lung injury:

the massive fluid requirements for resuscitation

from thermal burns and associated traumatic injuries will invariably worsen pulmonary function.

Patients may develop respiratory failure 1 to 2 weeks

following thermal injury. When delayed respiratory failure occurs, it is usually caused by infectious

complications either within the lung (pneumonia)

or at a remote site, giving rise to SIRS, which is the

major cause of death.

Inhalation of the toxic products of combustion

can induce parenchymal lung damage. The effects

may be immediate or delayed for hours. A common, serious pathophysiological effect of inhaling

combustion products is carbon monoxide intoxication. The marked affinity of carbon monoxide for

hemoglobin (> 200-fold higher than that of oxygen)

significantly reduces the oxygen-carrying capacity

of blood. A carbon monoxide concentration of 0.1%

in ambient air leads to a carboxyhemoglobin concentration of 50%. Carbon monoxide also shifts the

oxyhemoglobin dissociation curve to the left, which

further reduces oxygen delivery (DO2) to the tissues. Patients will complain of headache, nausea,

and exertional fatigue with moderate carbon monoxide exposure. Damage to the central nervous

system (CNS) may occur in up to 30% of affected

individuals unless they receive prompt therapy.

The classic “cherry red” coloration is not seen with

carboxy-hemoglobin concentrations lower than 40%.

A far more common manifestation is cyanosis.10

Lactic acidosis from reduced DO2 is a common finding with severe intoxication.

The therapy for respiratory injury caused by thermal burn is primarily supportive. Supplemental

oxygen and bronchodilators are used to treat hypoxemia and bronchoconstriction. Mechanical ventilation is required for patients with significant acute

lung injury. The use of positive end-expiratory

pressure (PEEP) increases the functional residual

capacity (FRC, the remaining lung volume after

passive exhalation) of the lung and allows the fraction of inspired oxygen (FIO2) to be reduced to

nontoxic levels. The U.S. Army Burn Center, Fort

Sam Houston, Texas, reports that a mode of ventilation (high-frequency, percussive) that employs repeated cycles of very rapid (several hundred per

minute) and small volume (less than the dead-space

volume) ventilations may be more efficacious. The

mortality rate found in such patients is markedly

less (16.4%) than in patients with similar thermal

insults who are treated with conventional mechanical ventilation (42.7%). The improved survival may

be due to both (a) the low airway pressures found in

high-frequency percussive ventilation (ie, there is

less potential for barotrauma) and (b) improved

removal of tracheobronchial secretions.11

Prophylactic steroids have not proven beneficial

for inhalation injury and may increase the risk for

subsequent infection. Likewise, antibiotic prophylaxis is no longer used; it may increase the risk

for resistant bacterial infection, and has not been

shown to reduce morbidity and mortality in clinical

trials.12

The treatment of carbon monoxide poisoning

involves supplying supplemental oxygen to reduce

the half-life of carboxyhemoglobin. (With 100%

oxygen, the half-life is reduced to 40 min, opposed

to 250 min in room air.) Hyperbaric oxygen may be

beneficial with severe intoxication; however, this

modality is not likely to be available in the combat

zone with the possible exception of aboard larger

naval vessels.

Chemical Warfare

Almost all chemical war gases cause respiratory

insufficiency and manifest a variety of effects that

could lead to respiratory failure (see Chapter 30,

Anesthesia for Casualties of Chemical Warfare

Agents, for a discussion of the respiratory effects of

war gases). The four major categories of war gases

are nerve, blister, choking, and blood agents. Decontamination procedures are not addressed in this

chapter; however, because acute respiratory failure

is a common cause of death in affected individuals,

medical personnel must ensure that the emergent

nature of the situation does not lead to hasty action

and inadvertent self-contamination.

Nerve Agents

Nerve agents have the potential to cause vast

numbers of casualties. Soldiers must have sufficient personal protective equipment and adequate

pharmacological prophylaxis. Military planners

must emphasize that medical officers may need to

care for mass casualties, all of whom may require

mechanical ventilation.

Nerve agents exert their effects by preventing

cholinesterase from hydrolyzing acetylcholine (previously released from the nerve terminal). This

allows for repetitive stimulation of the postsynaptic

receptor, which leads to rapid muscle fatigue. Inhalational or dermal exposures to nerve agents thus
Acute Respiratory Failure and Ventilatory Management

673

present as a cholinergic syndrome, the severity of

which depends on the amount of exposure. Respiratory effects of nerve agents include bronchoconstriction and bronchorrhea along with respiratory

muscle dysfunction. Organophosphate-induced seizures may further complicate the respiratory embarrassment produced by these agents.

Treatment includes administering both atropine,

which blocks the cholinergic receptors, and

pralidoxime chloride (2-PAM Cl), which binds to

organophosphate and most carbamate nerve agents,

releasing the cholinesterase and allowing normal

nerve function to resume. Airway control is of

paramount importance, as copious secretions may

prevent adequate ventilation and oxygenation. If

respiratory muscle function is adequate, oral or

nasopharyngeal suctioning may be all that is required. However, if respiratory muscle function is

poor, endotracheal intubation and mechanical ventilation may be required. Care must be taken to

ensure that the lungs are not exposed to the excessively high pressures that result from the intense

bronchoconstriction that follows significant nerve

agent exposure. Under these circumstances,

barotrauma may occur before bronchospasm has

subsided. Atropine, inhaled beta agonists such as

metaproterenol or terbutaline, and inhalational anesthetics all reverse bronchospasm.6

Blister Agents

Blister agents (vesicants), of which the mustards

are the best known, are alkylating chemicals that

are thought to act by damaging cellular DNA. This

leads to cell disruption and death; an intense inflammatory response causes blisters to form. Inhalation of vesicants produces severe tracheitis and

bronchitis. Symptoms may not develop for 4 to 6

hours, requiring medical personnel to observe casualties for delayed effects. Bronchopneumonia

frequently complicates the recovery of these patients. Progressive, irreversible respiratory insufficiency, developing over months to years after inhalation of mustard, has been described.13 It appears

to be caused by unrelenting fibrosis that leads to

stenosis of the entire tracheobronchial tree.

Choking Agents

The war gas that caused the most flagrant example of respiratory insufficiency in World War I

was phosgene, a choking agent. Choking agents

cause a severe form of respiratory insufficiency and

produce significant irritation of the lower respiratory tract. First used in World War I as a toxic agent,

phosgene produces distal airway and alveolar inflammation, which eventually causes pulmonary

edema. As with blister agents, the effects may be

delayed for up to 12 hours; minimal symptomatology may precede the development of fulminant

pulmonary edema.

Treatment is entirely supportive. Supplemental

oxygen and positive-pressure ventilation may be

necessary for severe cases. The effects are selflimiting, but due to the intense inflammatory response elicited, the patient’s condition may evolve

into ARDS.

Blood Agents

Blood agents such as hydrogen cyanide combine

with intracellular cytochrome oxidase and halt cellular respiration. Exposure to large amounts of

inhaled hydrogen cyanide causes death within minutes. Exposure to lesser amounts causes vertigo,

nausea, vomiting, headache, and tachypnea. Seizures and cardiopulmonary arrest may rapidly ensue if treatment is delayed.

Treatment involves administering amyl nitrate

by inhalation or sodium nitrite by vein. Nitrites

oxidize the iron moiety of hemoglobin to produce

methemoglobin. Methemoglobin scavenges cyanide from the circulating blood, which promotes a

concentration gradient for the removal of cyanide

from cytochrome oxidase. Intravenous sodium thiosulfate can be administered to provide free sulfur,

which will convert cyanide to the far-less-toxic thiocyanate ion. Mechanical ventilation with supplemental oxygen will aid in the resuscitation of apneic

casualties; however, expeditious treatment with

nitrites is the mainstay of therapy.6

Nuclear Warfare

Thermonuclear weapons produce their devastating effects via the release of massive amounts of

energy. This energy release produces casualties

with three types of injuries: blast, thermal, and

radiation. Blast and thermal injuries will be treated

in a manner identical to that previously discussed.

Neurovascular, gastrointestinal, and hematopoietic

syndromes are associated with nuclear radiation

injuries. Anesthesiologists and intensivists will

encounter the neurovascular and gastrointestinal

syndromes only rarely, as these are considered to be

uniformly fatal. The hematopoietic syndrome will

be the most common radiation injury requiring

medical care.
Anesthesia and Perioperative Care of the Combat Casualty

674

INDIRECT MECHANISMS OF RESPIRATORY INSUFFICIENCY

Respiratory failure in the combat casualty may

result from insults other than direct chest trauma.

Three of the most frequently encountered etiologies

are pulmonary aspiration, hydrostatic pulmonary

edema, and permeability pulmonary edema.

Pulmonary Aspiration

Medical personnel should assume that every combat casualty has a full stomach. The combination of

a traumatic injury and a full stomach puts soldiers

at risk for aspirating blood or regurgitated stomach

contents:

The soldier may have eaten just before being

wounded. Even if many hours have passed, pain

and anxiety greatly delay gastric emptying. The

important interval is not the time since the last

meal, but rather the time from the last meal to the

time of injury. Regurgitation and aspiration of stomach contents, particularly of volumes greater than

25 mL, with a pH less than 2.5, and in the presence

of solid food, place the casualty at high risk for

aspiration pneumonitis.14(p28)

Aspiration of gastric contents may be asymptomatic or cause several life-threatening syndromes.

The underlying common denominator in aspiration

is an altered level of consciousness. Many casualties will have head injuries that negate the protective airway reflexes, and many will require general

anesthesia or have neurosurgical catastrophes that

predispose to aspiration.15 However, other predisposing conditions (ie, neuromuscular or gastrointestinal disorders) are not common in this population.

Silent aspiration occurs when a small volume of

gastric contents is introduced into the trachea. This

may occur somewhat frequently in a civilian medical population—elderly and obtunded—who are

undergoing elective surgery, receiving therapeutic

narcotics, whose level of consciousness is depressed,

or while a nasogastric tube is being placed. In a

combat situation, silent aspiration is probably less

common.

When aspiration occurs, apnea or airway obstruction occur immediately. The acute chemical

injury damages the tracheal bronchial tree and alveoli. Pathologic evaluation immediately after aspiration shows bronchiolar epithelial degeneration,

pulmonary alveolar edema, and alveolar hemorrhage. Fibrinous exudate, focal atelectasis, and

neutrophilic infiltrates occur later. After 24 hours,

focal hemorrhage, atelectasis, empyema, fibrin-filled

alveoli, and pneumonitis are established.16 Bacterial pneumonitis can occur within 72 hours, and

lung abscesses may occur, usually after days to

weeks.

Injury occurs to both Type I and Type II pneumocytes. Type I pneumocytes undergo focal necrosis

and the basement membrane is exposed. Fluid fills

the alveolar and perivascular spaces. Type II cells

are initially edematous, then degenerate. Hyaline

membranes form by 48 hours. By 72 hours, alveolar

cells regenerate and the inflammatory process

abates.

Prevention is the best treatment for aspiration.

When prevention fails or is not possible, then making the correct diagnosis, removing large particulate matter, and providing appropriate supportive

measures will help improve morbidity and prevent

mortality.17

Immediate endotracheal intubation is required

when apnea occurs. Adequate ventilation should

be documented by measuring arterial blood gases

or by means of oximetry and capnography, which

are discussed later in this chapter.

Airway protection during intubation with

cricothyroid pressure should help prevent aspiration. The thumb and middle finger exert pressure

lateral to the cricoid cartilage, while the index finger pushes directly down on it. If the technique is

properly performed, this technique can prevent regurgitation when intragastric pressures rise to as

high as 50 cm H2O or more. Normal intragastric

pressure is usually less than 16 cm H2O so cricoid

pressure should be protective in most instances. As

soon as the patient is intubated, the cuff on the

endotracheal tube is inflated before manual pressure is released.18

Airway obstruction may be due to laryngospasm,

edema, mechanical obstruction by foreign material, bronchial inflammation, or bronchospasm.

Laryngospasm can be broken with either continuous positive airway pressure or a rapid-acting depolarizing muscle relaxant. If the laryngospasm

cannot be broken, surgical control of the airway is

mandatory. Nebulized racemic epinephrine may

improve airway edema.15

Suctioning often clears the airway of foreign debris, but if residual material remains, bronchoscopy

will be required. In many instances, aggressive

chest physiotherapy will help clear the small airways of particulate matter. This is contraindicated

in patients with head trauma or spinal cord injuries,

however.
Acute Respiratory Failure and Ventilatory Management

675

The treatment of aspiration pneumonia should

be prophylactic. Elevating the head of the bed to

prevent gastroesophageal reflux, neutralizing gastric contents, and prophylactic intubation are of the

utmost importance. Once aspiration has occurred,

adequate oxygenation is mandatory.17

On the battlefield, multiply injured casualties

will require intubation. Many will also require

urgent or immediate operative intervention.

Intubation will prevent further aspiration. Casualties with head injuries will require hyperventilation

as well.

Bronchial lavage is no longer believed to be indicated because it may worsen hypoxia. Positive

airway pressure should be used for diffuse

pneumonitis; however, its use in localized aspiration must be tempered against augmenting ventilation–perfusion mismatch. PEEP may be preferentially distributed to normally compliant units and

not improve the FRC in the affected lung region. It

must therefore be used with caution.

Appropriate fluid resuscitation should not be

tempered by the possibility of lung injury. Fluid

overload should be avoided but aggressive resuscitation must not. Cardiovascular stability should be

maintained with the proper use of inotropic agents

when indicated. In more severe cases, a flow-directed

pulmonary artery catheter may be beneficial because

it allows optimization of the hemodynamic status of

the patient, which should improve survival.

Glucocorticoids have no place in the treatment of

aspiration. Glucocorticoids suppress host defense

mechanisms and predispose the patient to infection. Prophylactic antibiotics are not used either, as

they do not prevent pneumonia and tend to select

out resistant organisms, thereby increasing morbidity and mortality.17

Hydrostatic Pulmonary Edema

Pulmonary edema is often associated with respiratory failure. The type of pulmonary edema must

be determined before the condition can be properly

treated. These types are hydrostatic pulmonary edema,

in which fluid accumulates in the presence of a

fairly normal blood–air barrier, and permeability

pulmonary edema, of which ARDS is the classic manifestation. Hydrostatic pulmonary edema occurs

because fluid accumulates in the presence of a fairly

normal blood–air barrier. In permeability pulmonary edema, fluid accumulation occurs because the

blood–air barrier is abnormal.19

Hydrostatic pulmonary edema is usually caused

by an increase in the intravascular filtration pressure within the pulmonary microvasculature. The

elevated filtration pressure increases the fluid flux

into the interstitium. If the capacity of the lymphatic system to reabsorb this fluid is exceeded,

then the fluid accumulates in the alveoli. Rarely,

fluid may accumulate in two other situations: if

plasma oncotic pressure is reduced or if the capacity of the lymphatic system to remove fluid is reduced. The intravascular pressure must rise above

7 to 10 mm Hg for water to flood the interstitial

space.

With the increased flux of fluid into the interstitium, the fluid moves down a negative interstitial

pressure gradient toward the bronchovascular cuffs.

This is where the pulmonary lymphatics begin. If

lymphatic uptake is decreased, fluid accumulates

around the bronchoalveolar cuff until the interstitial pressure is greater than the airway pressure, at

which time fluid enters the alveolus. This is typically seen when the pulmonary artery occlusion

pressure (PAOP) exceeds 20 mm Hg.

In the civilian population, the causes of hydrostatic pulmonary edema include cardiac dysfunction, pulmonary venous occlusive disease, neurogenic pulmonary vasoconstriction, pulmonary

arterial embolization with air, thrombus, or fat;

however, these are rarely seen in young, healthy

soldiers. In the combat casualty, the most common

causes of hydrostatic pulmonary edema are

iatrogenic. Asthma and foreign bodies that cause

airway obstruction, and pulmonary lymphatic obstruction may also cause hydrostatic pulmonary

edema. Clinically, the classic description is that of

respiratory distress with pink, frothy sputum and

arterial hypoxemia. In trauma patients, this occurs

with massive head injury, chest injury, or large

amounts of volume resuscitation.20

Patients will occasionally present less dramatically with complaints of mild chest tightness or a

pressure sensation, a sensation of being unable to

catch the breath, and cough. As the capillary pressure continues to increase, and as the fluid flux

becomes more pronounced, the patient will become

more symptomatic. The respiratory rate increases

and the ventilatory pattern becomes labored. This

increases the work of breathing required to achieve

adequate lung expansion. Respiratory failure will

occur because of muscular exhaustion.

Alveolar flooding is accompanied by arterial

hypoxemia. Fluid-filled air spaces prevent the passage of gas into the capillary. These air spaces have

low ventilation-to-perfusion ratios (ventilation–

perfusion mismatch). As the mismatch increases,

the effectiveness of hypoxemic pulmonary vaso-
Anesthesia and Perioperative Care of the Combat Casualty

676

trauma was described in 1932,22 and ARDS was

defined in 1967.23 For ARDS to occur, the capillary

endothelium of the pulmonary vasculature must be

injured. This results in dyspnea, hypoxemia, decreased pulmonary compliance, and bilateral pulmonary infiltrates. Pulmonary edema is present

but not associated with an increased hydrostatic

pressure; it is caused by increased permeability

resulting from diffuse alveolar–capillary endothelial injury. ARDS is a common problem affecting

previously healthy people. The mortality rate is

high: despite vigorous supportive care, it can be

greater than 40%.24

The syndrome is associated with a wide variety

of disease states with multiple underlying etiologies, all demonstrating a single clinical pattern.

ARDS can be caused by all types of shock (Exhibit

25-2). A 2.2% incidence of ARDS has been reported

constriction decreases and profound arterial hypoxemia will ensue. Formerly, oxygen was believed to need to diffuse through an abnormally

thick layer of water before it reached the red blood

cells, but compared to ventilation–perfusion mismatch, this is probably a minor impediment to the

exchange of respiratory gases.

The fluid tends to accumulate first in the dependent portions of the lung. Because the pulmonary

blood and air flows to the dependent areas are

disproportionally small, this fluid accumulation exaggerates the normal propensity for alveoli in the

dependent part of the lungs to be underventilated.

The pulmonary blood flow is redistributed to less

edematous, nondependent alveoli. The FRC decreases with increased critical closing pressure of

the alveoli. Other unrelated conditions that decrease FRC (eg, increased intraabdominal pressure,

upper abdominal or thoracic incision, and the supine position) can compound the hypoxemia.

The treatment of hydrostatic pulmonary edema

must both reverse the changes caused by fluid accumulation and eliminate the underlying disorder

that promotes fluid accumulation. The supportive

therapy should minimize arterial hypoxemia and

decrease the work of breathing. Supplemental oxygen and positive airway pressure are the mainstays

of treatment. Administration of supplemental oxygen through nasal prongs or a face mask is useful.

However, endotracheal intubation is often required

as respiratory failure progresses. If the arterial

partial pressure of oxygen (PaO2) does not increase

after supplemental oxygen therapy is added, then

continued hypoxemia is caused by groups of alveoli

with low ventilation–perfusion ratios. Positive airway pressure is then delivered as PEEP or CPAP.

This will increase the PaO2 by increasing the FRC of

the lungs. (The alveoli are now being ventilated

because a higher pressure is being used to force

respiratory gas into them.) To decrease the work of

breathing, both positive airway pressure and assisted ventilation can be utilized. Positive airway

pressure restores lung volume, increases compliance, and increases the cross-sectional area of the

airways. It also reduces airway resistance by splinting the airway lumen open. Flow rates will decrease as ventilation becomes less labored, thereby

converting a higher-resistance, turbulent flow into

a lower-resistant, laminar flow pattern.21

Adult Respiratory Distress Syndrome

Lung injury has plagued successful resuscitation

of the trauma patient. Lung injury associated with

EXHIBIT 25-2

ETIOLOGY OF SHOCK THAT INDUCES

THE ADULT RESPIRATORY DISTRESS

SYNDROME

Burns

Fat emboli

Lung contusion

Head trauma

Near drowning

Septic states

Inhalation of toxic gases:

Smoke

Nitrous oxide

Ammonia

Chlorine

Phosgene

Cadmium

Aspiration of gastric contents

Drug ingestion

Pancreatitis

Multiple transfusions

Disseminated intravascular coagulation

Bowel infarction
Acute Respiratory Failure and Ventilatory Management

677

In casualties with traumatic injuries.25 The syndrome is more common in casualties with bilateral

chest trauma and extensive lung injury than it is in

casualties with a localized lung contusion.

Pathophysiology of Alveolar Injury

The normal structural integrity of the alveolus is

disrupted in patients with ARDS. Type I pneumocytes cover approximately 95% of the alveolar

surface area while Type II pneumocytes cover the

remaining 5%. Because of their greater number,

Type I pneumocytes are more likely to be injured.

Within 24 hours of injury, Type I pneumocytes are

destroyed, leaving a denuded basement membrane.

Type II pneumocytes, which appear to be more

resistant to initial damage, then proliferate and

form a continuous layer that covers the previously

denuded basement membrane. In addition, the

denuded surface may allow aggregates of plasma

proteins, cellular debris, fibrin strands, and remnants of surfactant to adhere, which forms the characteristic hyaline membrane. Over the next several

days, the alveolar septum thickens, and not only

inflammatory cells but also reparative cells proliferate. Hyaline membranes organize, and microatelectasis occurs. The capillary endothelial damage becomes more apparent. Irregularities of the

endothelial surface with focal cytoplasmic swelling

can be seen, and fibrosis is apparent in the respiratory ducts and bronchioles.26

Starling’s equation predicts the fluid flux across

a semipermeable membrane. It describes the balance between hydrostatic and oncotic pressures

acting in opposition across the endothelial barrier.

There are two driving forces (the pressure within

the capillary, Pc, and the pressure within the

interstitium, Pi) and two retaining forces (the colloid osmotic pressure within the capillary, πc, and

the interstitium, πi

). The symbol σ, which is known

as the reflection coefficient, represents the impermeability of the membrane to a given substance (ie,

if σ = 1, the membrane is completely impermeable;

while if σ = 0, the membrane is completely permeable). K is a constant representing the filtration

coefficient.

Starling’s equation states:

fluid flux = K[(Pc – Pi) – σ (πc – πi)]

Theoretically, the interstitial hydrostatic pressure

is slightly negative due to the elastic properties of

the lung; therefore, progressively more negative

fluid pressures increase the flux into the alveolar

space. The small amount of fluid filtered into the

interstitial space is readily removed by the extensive pulmonary lymphatic system. Hydrostatic

pulmonary edema occurs when the factors favoring

fluid flux across the capillary membrane exceed

those designed to protect the lungs from developing edema.19

The pulmonary edema that characterizes ARDS

is caused by alteration of Starling’s forces. This

alteration is usually due to an abnormally high

permeability coefficient; the abnormality is made

worse when the capillary hydrostatic pressure increases. The latter abnormality may manifest as

elevated pulmonary capillary wedge pressure.

Decreased colloid oncotic pressure can be caused by

severe hypoproteinemia from overhydration with

intravenous crystalloid fluid, liver failure, or the

nephrotic syndrome; however, it is rarely responsible for lung edema.

Finally, increased interstitial colloid oncotic pressure can occur with increased alveolar capillary

membrane permeability (large protein molecules

leak out into the interstitium where their oncotic

properties attract fluid from the vascular bed). This

may be the primary mechanism responsible for the

development of pulmonary edema in ARDS. The

altered permeability allows the free movement of

fluid and protein from the intravascular space, to

the interstitial space, to the intraalveolar space.

Edema forms at a rate that exceeds the lymphatic

system’s ability to remove it.

The alteration of the integrity of the alveolar

capillaries is believed to result from injuries due to

the adverse effects of (a) tumor necrosis factor and

leukokinin I, which are released from activated

macrophages, and (b) oxygen free radicals, which

are released from neutrophils. Intravascular activation of complement leads to stimulation of neutrophils, sequestration within the capillaries, and

subsequent endothelial damage. Patients with ARDS

have increased levels of serum C-5A, the activated

fifth component of the complement cascade.26

Release of C-5A by the alternate pathway causes

macrophages and neutrophils to aggregate. The

neutrophils release oxygen free radicals; prostaglandins; and granules that contain protease, elastase,

coagulase, pepsins and lysozymes. Damage to the

basement membrane occurs and increased permeability follows. This allows nonhydrostatic pulmonary edema to form. Arachidonic acid metabolites

affect vascular permeability, vascular tone, and airway reactivity, which causes further vasoconstriction and bronchoconstriction.
Anesthesia and Perioperative Care of the Combat Casualty

678

An additional factor resulting in alteration of the

integrity of the alveolar membrane in casualties

with massive CNS injury is massive sympathetic

discharge, which affects the pulmonary veins. This,

in turn, causes profound pulmonary hypertension,

which mechanically disrupts the junctions between

pulmonary capillary endothelial cells.

Pathophysiology Resulting in Abnormal Gas

Exchange

The abnormal gas exchange that occurs in ARDS

is due to the increase in extravascular lung water,

which tends to close small groups of peripheral

alveoli and cause intrapulmonary shunting. This

process could be compounded over time by the

progressive, extensive fibrosis that occurs in most

of these patients. In one study,27 researchers found

that by using multiple, inert-gas elimination techniques in patients with ARDS, some degree of ventilation–perfusion mismatch occurred in 40% of

patients. There was no evidence of a diffusion

abnormality as it applies to respiratory gas exchange.

ARDS also causes changes in lung mechanics.

Both the FRC and pulmonary compliance decrease.

Loss of surfactant causes alveolar collapse, leading

to further decreases in both FRC and pulmonary

compliance. In addition to surfactant abnormalities, flooding of the alveoli decreases alveolar volume and causes further atelectasis. Compliance is

further reduced by interstitial and alveolar edema,

fibrosis, and the abnormal surfactant.

Clinically, during phase I, the patient will be

dyspneic and will demonstrate a respiratory

alkalosis with tachycardia and tachypnea (Table 25-

1). A latent period, phase II, will occur, lasting from

6 to 48 hours after the injury, during which the

patient will appear stable and may appear to be

improving. During phase II, the patient will begin

to demonstrate an increase in the work of breathing,

with hyperventilation and hypocarbia; the lungs

become less compliant due to both movement of

fluid into the alveoli and loss of surfactant. Decreased alveolar volume and widespread atelectasis

are the consequences of these changes (Table 25-2).

Physical examination will demonstrate scattered

rales and evidence of the use of the accessory muscles

of respiration. The initial chest X-ray examination

will be normal, but subsequent radiographs will

demonstrate increases in interstitial markings. With

continued progression of the disease, the patient

will develop acute respiratory failure (phase III).

Lung compliance will be markedly decreased due

to interstitial and alveolar edema, fibrosis, and abnormal surfactant. Loss of the normal surfactant

leads to a decrease in the FRC and thus a further

decrease in compliance. Further decreases in the

FRC increase the alveolar–arterial oxygen difference and worsen the hypoxia.

The chest radiograph will demonstrate a diffuse

interstitial pattern and, in fact, pneumonia is often

difficult to rule out. At this time, bronchoalveolar

lavage for diagnosis may be indicated to identify

the pneumonic process.

The patient may improve at this time. The physical findings will resolve and the chest radiograph

will return to normal. More commonly, however,

the disease progresses with severe unresponsive

hypoxemia, increased intrapulmonary shunting of

blood, and metabolic and respiratory acidosis. The

radiograph demonstrates honeycombed, patchy,

and ill-defined nodular densities.

Treatment

Treatment of the patient with ARDS encompasses

measures to (a) prevent death from respiratory failure, (b) minimize further lung injury, (c) provide

general support, and (d) recognize and treat complications.

The goal of therapy is to provide adequate oxygenation at the lowest possible FIO2. High inspired

oxygen concentrations, as well as high airway pressures, have the potential to significantly exacerbate

the acute lung injury.

Initially, the lowest FIO2 needed to provide an

arterial hemoglobin saturation (SaO2) of 90% or

more is used. Continuous pulse oximetry is used to

monitor therapy. Decreasing the FIO2 to 50% is

desirable, and to achieve it, end-expiratory pressure is frequently used. PEEP is begun at 5 cm H2O

and increased incrementally with careful attention

to cardiac output, pulmonary compliance, and peak

inspiratory pressure. The medical officer’s clinical

judgment may be all that is available to assure

optimal oxygenation.

Mechanical ventilation is used to deliver increased FIO2 and increased tidal volumes. Tidal

volumes of 10 to 15 mL/kg should be used initially.

Careful attention is required to prevent the increased peak inspiratory pressure from causing

barotrauma.

The need for high peak inspiratory pressure may

be dictated by decreased compliance of the ARDS

lung. However, other causes that may give rise to

high peak inspiratory pressure are endotracheal

tube displacement, pneumothorax, increased pleu-
Acute Respiratory Failure and Ventilatory Management

679

TABLE 25-1

CLINICAL FINDINGS IN ADULT RESPIRATORY DISTRESS SYNDROME

Phase Findings

Phase I: Normal auscultatory examination

Acute Injury Normal chest X-ray examination

Tachycardia

Tachypnea

Respiratory alkalemia on arterial blood gas testing

Phase II: Minor abnormalities on auscultatory examination

Latent Period (6–48 h) Minor abnormalities on chest X-ray examination

Tachycardia and tachypnea persist

Increased work of breathing

Respiratory alkalemia

Increased PAO2 – PaO2

Phase III: High-pitched rales to auscultation

Acute Respiratory Failure Diffuse infiltrates on chest X-ray examination

Marked tachypnea and dyspnea

Decreased lung compliance

Worsening oxygenation and ventilation

Phase IV: Severe, unresponsive hypoxemia

Terminal Abnormalities Increased intrapulmonary shunting

Severe metabolic and respiratory acidemia

PAO2 – PaO2: alveolar-arterial difference in partial pressure of oxygen

TABLE 25-2

PATHOPHYSIOLOGY OF THE ADULT RESPIRATORY DISTRESS SYNDROME

FRC: functional residual capacity; PAOP: pulmonary artery occlusion pressure

Findings Mechanisms

Refractory hypoxemia Increased intrapulmonary shunting

Decreased FRC

Release of inflammatory mediators

Diffuse infiltrates on chest X-ray examination Alveolar edema

Atelectasis

Inflammatory cell infiltrates

Normal PAOP Endothelial damage results in capillary leakage

Decreased pulmonary compliance Edema

Atelectasis

Marked increase in extravascular lung water
Anesthesia and Perioperative Care of the Combat Casualty

680

erate dyspnea on exertion. In the majority, the chest

X-ray examination will return to normal, as will

their lung volumes. Resting arterial blood gases

will tend to be normal but with exercise, approximately half of these patients will have some decrease in their PaO2. Surprisingly, the typical ARDS

patient does not die of respiratory insufficiency but

of complications of unrelenting sepsis with failure

of other organ systems.30

Although not presently applicable to combat situations, the use of extracorporeal membrane oxygenation with low-frequency positive pressure ventilation may be of some benefit to patients with ARDS.

Although several studies of note have shown no

improvement in survival when extracorporeal membrane oxygenation was used for oxygenation, others have used the apparatus with low-frequency

positive pressure ventilation to some success. Lung

function improved in 73% of patients and 49% survived, compared with the previous mortality rate of

91%.31 An intra–vena caval blood oxygen–extracorporeal carbon dioxide removal device is presently

undergoing clinical trials. Preliminary data indicate that there is no improvement in survival compared with conventional therapy.32

ral effusion, increased lung edema, bronchospasm,

mucous plugging, and high flow rates. Adjusting

the tidal volume, the level of PEEP, or using paralytic agents to relax the patient’s respiratory muscles

may be required to decrease barotrauma. The mode

of ventilation may be either intermittent, mandatory ventilation (IMV) or assist control (AC), both of

which are discussed later in this chapter. Neither

mode has been shown to be superior. The mode

with which the operator has the most experience

should be the mode used.

The use of glucocorticoids in the treatment of

ARDS is not resolved. In the past, high-dose glucocorticoids have been advocated, but a prospective

randomized trial published in 198728 reported that

no benefit was seen from the use of glucocorticoids.

However, a meta-analysis published in 199529 suggests that a subset of patients may benefit from

corticosteroids administered during the fibroproliferative phase of the disease process.

Even with aggressive, intensive care, the mortality rate for ARDS remains approximately 50%. Of

patients who survive the disease and its complications, most will become clinically asymptomatic. A

small percentage, however, will have mild-to-modDIAGNOSING RESPIRATORY FAILURE

DO2 to tissues for metabolic function. Cyanosis is

only detectable when the patient’s blood contains at

least 5 g of deoxygenated hemoglobin per deciliter

of blood. Similar findings (ie, signs and symptoms

of hypoxemia) are noted when the level of methemoglobin reaches 1.5 g/dL, which may be seen

following treatment for cyanide toxicity.6 Typically, CNS effects are prominent with significant

hypoxemia. Confusion, restlessness, and loss of

judgment are common manifestations. The lack of

available oxygen leads to increased sympathetic

tone as the body attempts to compensate for inadequate DO2 to the tissues. Lactic acidosis with a

compensatory respiratory alkalosis becomes prominent as cells convert to anaerobic metabolism to

provide for energy needs.

The major causes of hypoxemia in the trauma

patient are a direct result of abnormalities in ventilation–perfusion relationships within alveolar capillary units. The deoxygenated blood that perfuses

the alveolar capillaries in areas of hypoventilation

within the lung cannot be normally oxygenated.

The oxygenation deficit in this circumstance can be

corrected by supplemental oxygen. This will increase the relative amount of oxygen within the

alveoli in the region of low ventilation.

Because the causes of respiratory failure are so

varied, astute physicians always search for incipient respiratory failure in their patients. The term

acute respiratory failure comprises disorders of oxygenation or ventilation or both. Its definition, likewise, has both oxygenation and ventilatory components:

• hypoxemia: while breathing room air, the

partial pressure of oxygen (PO2) is 50 mm

Hg or less; and/or

• ventilatory failure: the inability to ventilate

sufficiently to maintain arterial blood partial pressure of carbon dioxide (PaCO2) less

than 50 mm Hg.21

Although disorders of oxygenation and ventilation

frequently coexist, consideration of each as a separate entity allows for a clearer understanding of the

pathophysiological processes that lead to respiratory failure.

Hypoxemia

The signs and symptoms of hypoxemia are the

effects of, and the body’s response to, insufficient
Acute Respiratory Failure and Ventilatory Management

681

Although a number of pathophysiological processes produce hypoventilation, atelectasis from

direct trauma to the lung parenchyma is the most

common. Overly aggressive volume resuscitation

with increased lung water is also frequently encountered in the setting of trauma. The second

mechanism for the development of arterial hypoxemia, that of right-to-left intrapulmonary shunting

of blood, can be thought of as the extreme form of

altered ventilation and perfusion. In this instance,

pulmonary arterial blood traverses capillaries in

regions of complete alveolar collapse or regions

that receive no ventilation from airway obstruction.

Supplemental oxygen does not correct the oxygenation deficit. Correction is accomplished by inflating these collapsed alveoli, and it is necessary to

resort to either continuous positive airway pressure

via face mask or endotracheal intubation to improve oxygenation.

In combat medical facilities, supplemental oxygen is delivered from a tank. Oxygen sieves(concentrators that can remove and concentrate oxygen

from ambient air) will be available in future conflicts to supply supplemental oxygen. In addition

to the signs and symptoms of hypoxemia, assessment of the patient’s degree of oxygenation requires arterial blood-gas measurement and pulse

oximetry. The echelon of combat medical care that

will have blood-gas monitoring capabilities is unclear; however, transportable pulse oximetry is available and could be utilized at mobile army surgical

hospitals (third echelon), combat support hospitals

(third echelon), and possibly even at the clearing

station (second echelon).

Ventilatory Failure

Ventilatory failure may result from a number of

different pathological processes. The two disorders

most commonly associated with respiratory insufficiency leading to ventilatory failure are (1) CNS

depression from trauma or drug effect and (2) compromise of the respiratory function of the chest

wall. Disorders of the chest wall (eg, flail chest)

may occasionally lead to ventilatory failure manifested by hypercarbia. However, associated abnormalities of oxygenation tend to represent the more

life-threatening condition. Clinical signs and symptoms of hypercarbia are similar to those noted with

hypoxemia, but with these exceptions: cyanosis is

absent while oxygenation is maintained, and

obtundation is more common than agitation. As it

does with failure of oxygenation, optimum determination of the adequacy of ventilation rests on the

physician’s interpretation of arterial blood-gas determinations. Portable capnography provides a

reasonable estimate of arterial carbon dioxide content and may prove useful in situations in which

blood gas determinations are not available.21

Combined Hypoxemia and Ventilatory Failure

in Postoperative Casualties

Postoperative pulmonary complications are

among the commonest causes of morbidity and

mortality in this patient population. Of all the

potential respiratory complications, atelectasis is

easily the most common: it may account for up

to 90% of postoperative respiratory complications.33 The degree of involvement may range from

a small, insignificant group of airways to complete

collapse of an entire lung. Other less common but

frequently more life-threatening complications

include pneumonia, bronchospasm, pulmonary thromboembolic disease, and respiratory failure. It is possible to define the various abnormalities with a combination of radiographic, laboratory,

and clinical features. Chest X-ray examinations,

blood-gas measurements, and chest auscultation remain the most valuable techniques to define

pulmonary abnormalities and determine the need

for more-invasive measures such as bronchoscopy, endotracheal intubation, or pulmonary

arteriography.34

Upper abdominal and thoracic surgery carry the

greatest risk for postoperative pulmonary dysfunction. Splinting to ease pain reduces the patient’s

ability to cough and breathe deeply, both of which

predispose to distal airway plugging and collapse.

The splinting results in a reduced vital capacity that

leads to hypoventilation, while the airway plugging causes atelectasis and hypoxemia. Another

important factor, a direct result of general anesthesia, is depression of mucociliary transport. Abnormal ciliary action and production of mucus are both

worsened by lengthening anesthesia time. Cigarette smoking potentiates this abnormality.

Surgical procedures also predispose to premature closure of the distal airways. Supine positioning, increased abdominal girth and breathing at

reduced lung volumes are nonpulmonary factors

that contribute to premature airway closure. Interstitial edema, airway obstruction from secretions

and bronchoconstriction, and loss of surfactant are

pulmonary factors that tend to promote airway

closure and atelectasis.34

A routine program of respiratory therapy before,

during, and after surgery can reduce the number of
Anesthesia and Perioperative Care of the Combat Casualty

682

postoperative respiratory complications and improve patient outcome when they do arise. The first

few hours after the operation are the most critical

for preventing respiratory complications. Alveolar

collapse, with the resulting loss of FRC, may be

prevented or reversed by deep breathing. Maneuvers that utilize forced exhalation (eg, blow bottles)

do not effectively prevent airway collapse and may,

in fact, promote this problem if an ineffective inspiration precedes the forced exhalation. Deep-breathing exercises, with inspiration to total lung capacity, are easily the most effective, cost-efficient means

to prevent and reverse atelectasis (and hence, most

pulmonary complications). Incentive spirometers

allow patients to participate in their therapy and

free the respiratory therapist to perform other duties. Most studies have found that intermittent

positive-pressure breathing is, at best, equal to, and

in most cases, inferior to incentive spirometry as a

prophylactic measure to prevent postoperative pulmonary complications.33

The likelihood that a patient will develop postoperative respiratory complications is directly related to the type of surgical procedure and the

duration of surgery and anesthesia; the patient’s

smoking history, preexisting pulmonary disease,

obesity, and overall physical condition; and other

factors.35 For the most part, soldiers are in excellent

physical condition and do not demonstrate significant preexisting lung disease.

Although exsanguination is the most common

cause of early death among combat casualties, medical officers must not forget that the first step to be

taken in the management of any trauma victim is to

assure a patent airway.36 Respiratory failure must

be recognized and treated promptly. Upper airway

obstruction may not be obvious on initial assessment in the field, and may recur anytime during the

medical-evacuation process. All military medical

personnel should be trained in simple maneuvers to

relieve upper airway obstruction. Should a

hypovolemic trauma casualty require endotracheal

intubation and positive-pressure mechanical ventilation, it is especially important that cardiovascular

resuscitation be continued, to mitigate against the

possible adverse effects of the positive pressure.

Supportive Care

Respiratory care begins with the use of supplemental oxygen. The most common methods to

employ this drug are nasal cannulae and face masks.

The FIO2 actually achieved with a nasal cannula is

dependent upon the patient’s inspiratory flow rate

and respiratory rate. A variety of masks are available for oxygen therapy. Higher percentages of FIO2

may be obtained by use of the partial rebreathing

mask or the nonrebreathing mask. The latter is the

type most frequently applied to patients following

general anesthesia, and is available in deployable

medical facilities, including field echelons. The use

of such a mask, which utilizes three unidirectional

valves, ensures that carbon dioxide will not be

rebreathed.

The next most common form of respiratory care

used for patients is incentive spirometry. The success of this therapy in expanding the patient’s FRC

depends on both achieving adequate inspiratory

volume and sustaining maximum inspiratory effort. Although preoperative teaching is often done

in the setting of elective surgery, this obviously will

not be possible in the combat casualty setting.

Intratracheal suctioning is important in maintaining the patency of the proximal airway and in

preventing secretions from obstructing the alveoli.

This is particularly true in the casualty with a penetrating chest wound, where the potential exists for

bleeding into the airway. The casualty can drown

in his own blood. Intratracheal suctioning is not

entirely benign: it can be associated with complications such as trauma to the tracheal mucosa

with resultant hemorrhage, hypoxia, and the vasovagal response leading to bradycardia and

hypotension.

Endotracheal Intubation

Although most patients who require endotracheal intubation will also require mechanical ventilatory support, there are clinical situations in which

intubation should proceed independent of the criteria defining respiratory failure. Intubation is required to provide airway protection and to prevent

aspiration in a patient who is semicomatose. The

treatment of upper-airway obstruction following

direct maxillofacial trauma and the prevention of

complete airway obstruction following thermal burn

injuries are two other clinical examples. A full

discussion of the methods of endotracheal intubation

is found in Chapter 3, Airway Management.

Prolonged endotracheal intubation brings with it

many possible complications. The posterior

MANAGING RESPIRATORY FAILURE
Acute Respiratory Failure and Ventilatory Management

683

arytenoid cartilages are the most common sites for

laryngeal damage, which is caused by the anterior

bend imposed on the endotracheal tube at this point.

Although the definition of prolonged translaryngeal

intubation and the timing of tracheostomy are not

yet answered in the medical literature, most clinicians consider 14 to 21 days to be a safe period

before performing a tracheostomy.37

The complications of an elective tracheostomy

are generally greater than those of translaryngeal

intubation, although the overall incidence of

complications is still low (3%). Early stomal bleeding is common; bleeding after 48 hours is more worrisome because it may indicate a catastrophic

complication: a fistula between the trachea and the

innominate artery. Tracheal–innominate artery

fistulae occur infrequently but have a high mortality.

An increased incidence of bacteremia and

nosocomial pneumonia are other problems associated with tracheostomy. Studies38 have shown that

up to 87% of patients with tracheostomies experience chronic aspiration. For example, tracheal

stenosis is a common, clinically significant complication. The reported incidence varies, but exceeds

that seen in patients with endotracheal tubes.37

The most common site for tracheal stenosis is the

stoma itself. A 75% reduction in the diameter of the

trachea may occur before symptoms are manifested.

The patient who is developing tracheal stenosis—

who experiences stridor at rest—probably has a

tracheal diameter less than 5 mm.

PHYSIOLOGICAL EFFECTS OF MECHANICAL VENTILATION

Once an endotracheal tube is used for ventilation, the patient’s natural mechanism for the warming and humidification of inspired air are bypassed.

Immediately following intubation and the institution of mechanical ventilation, patients may experience physical and psychological discomfort, which

results in coughing and agitation. Most patients—

especially those who are awakening, alert, or mildly

obtunded—attempt to “fight” the ventilator.39

Nearly constant medical supervision is required,

and restraints may be necessary to avoid selfextubation.

Pulmonary Effects

Positive pressure applied during inspiration results in an alteration of the normal ventilation–

perfusion matching. During spontaneous ventilation, most pulmonary blood flow and ventilation

occurs in the dependent parts of the lungs. This

relationship is changed during mechanical ventilation such that the greatest ventilation now occurs in

the superior aspects of the lung. This is most likely

the result of changes in the diaphragmatic shape

and motion following positive airway pressure.

The result is an increase in the physiological dead

space following the institution of mechanical

ventilation.

The use of positive-pressure ventilation may also

create changes in the lung mechanics. Reductions

in the FRC and pulmonary compliance may result

in an increase in the work of breathing, and increased minute ventilation requirement.

The application of expiratory distending pressure results in an improvement of gas exchange and

pulmonary compliance secondary to an increase in

lung volumes. The mechanism of the increase in

FRC is not clearly known but probably is the result

of one or more of the following:

• an increase in the transpulmonary pressure;

• “recruitment” of atelectatic alveoli, resulting in their reexpansion; or simply

• the maintenance of alveolar patency, which

was achieved during inspiration.

It is unlikely that the application of PEEP can open

atelectatic alveoli that were not reexpanded during

positive-pressure ventilation. Expiratory distending pressure also causes a decrease in the closing

volume below the FRC, which mitigates against

airway collapse during exhalation.

Conversely, an increase in lung volume may be

detrimental if the FRC exceeds the normal volume.

Excessive increases in FRC reduce pulmonary compliance and increase the pulmonary vascular resistance and dead space. Contrary to earlier beliefs,

applying expiratory distending pressure actually

increases total lung water, although oxygenation

usually improves.

Cardiovascular Effects

The effects of expiratory distending pressure can

be divided into (a) the effects on pulmonary vascular resistance and (b) the effect on cardiac output.

The pulmonary vascular resistance is lowest when

the FRC is normal. If the FRC is returned to normal

by the recruitment of atelectatic alveoli, and venous
Anesthesia and Perioperative Care of the Combat Casualty

684

The effect of expiratory distending pressure on

ventricular afterload differs between ventricles. An

increase in right ventricular afterload is not predictable and depends upon the amount of increase in

the pulmonary vascular resistance. At higher levels

of PEEP (> 15–20 cm H2O), right ventricular dilation

occurs resulting in a shift of the intraventricular septum and possibly contributing to a decreased left

ventricular stroke volume and cardiac output.40 In

this setting, the PAOP or pulmonary capillary wedge

pressure (PCWP) may not reflect the true left ventricular end diastolic volume. As a result of an increased pleural pressure, the left ventricle may be

compressed (ie, assisted). A failing left ventricle performs better when the afterload has been reduced.

Renal Effects

High levels of expiratory distending pressure

have been associated with decreased urinary output. Animal studies comparing continuous, positive airway pressure to spontaneous breathing (ie,

IMV) with PEEP failed to implicate reduced cardiac

output as the etiologic factor.41 Two possible explanations are (1) an increase in venous pressure, resulting in a decreased glomerular filtration rate and

(2) an alteration of the distribution of intrarenal

blood flow.

admixture is decreased, hypoxic pulmonary vasoconstriction will be reduced. In contrast, if the

alveolar pressure is increased beyond normal (thoracic overinflation), pulmonary capillary pressure

will rise, resulting in an increase in the pulmonary

vascular resistance.

The varying effect of expiratory distending pressure in different patients depends on thoracic compliance, which governs the transmission of pressure to the pleural space and great vessels. When

the pulmonary compliance is low (eg, in a patient

with ARDS), a minimal amount of expiratory distending pressure is transmitted to the pleural space.

Thus, these patients frequently tolerate high levels

of PEEP relatively well. If, however, the thoracic

compliance decreases from abdominal distention

or postoperative atelectasis, much of the expiratory

distending pressure will be transmitted to the pleural space. This results in a potentially significant

decrease in both venous return and cardiac output.

The treatment is to increase the peripheral venous

pressure, usually by volume administration. The

extent to which this complication occurs may also

be minimized by permitting spontaneous breaths

through the use of IMV. Negative-pressure, spontaneous breaths serve to minimize the effect of

expiratory distending pressure by augmenting

venous return.

COMPLICATIONS FROM MECHANICAL VENTILATORY SUPPORT

A variety of complications may occur during

mechanical ventilation. Two of the most important

are cardiovascular depression and barotrauma.

First, positive-pressure ventilation necessarily increases intrathoracic pressure. The increased intrathoracic pressure reduces venous return to the

heart, and, therefore, right ventricular preload. This

has two effects: (1) the reduction in preload results

in a decrease in cardiac output; and (2), right-ventricular afterload increases, probably as a result of

direct compression of the pulmonary vasculature.

These two detrimental effects act in concert to reduce cardiac output, and both effects tend to be

magnified by hypovolemia and PEEP.21

The second major complication of positive-pressure ventilation is barotrauma. The spectrum of

barotrauma extends from pulmonary interstitial

emphysema through pneumomediastinum, pneumothorax, and subcutaneous emphysema.42 Current theories on barotrauma relate the initial event

as alveolar rupture with dissection of air along the

vascular sheath to the mediastinum. Once air enters the mediastinum, it may track along the fascial

planes into the pleural space, subcutaneous tissue,

or retroperitoneum.43 It is the development of

pneumothorax, and in particular, of tension pneumothorax, that represents the greatest threat to the

patient. Peak airway pressure is believed to be the

primary factor related to the development of

barotrauma. No barotrauma was found in one

series of patients whose peak airway pressure could

be maintained at less than 50 cm H2O.42 Although

experts debate the maximal pressure that can be

tolerated without barotrauma, the practice of minimizing peak airway pressure to forestall the development of barotrauma is standard for managing

patients with respiratory failure.

The finding of pulmonary interstitial emphysema on chest X-ray examination should alert the

clinician to the real possibility that the patient may

soon develop a pneumothorax. Because pneumothorax may present abruptly, the diagnosis should

be made on the basis of clinical examination. The

combination of respiratory distress, hypotension,
Acute Respiratory Failure and Ventilatory Management

685

hyperresonance, diminished breath sounds, and

tachycardia should lead the clinician to evacuate

the presumed pneumothorax with a large-bore

needle placed in the second or third intercostal

space in the midclavicular line on the affected side.

Following immediate decompression by needle

drainage, a tube thoracostomy should be performed, with the tube connected to a Heimlich

valve or a water seal to preclude reaccumulation of

air in the pleural space.

ETHICAL DILEMMAS IN USING LIMITED LIFE-SUSTAINING THERAPY

“Battlefield military medicine has a threefold

mission: to save lives, to alleviate suffering, and to

return soldiers to duty.”15(p192) The question exists

as to whether mechanical ventilation is a useful

component of the medical officer’s armamentarium

for the treatment of combat casualties. In other

words, is it likely that the casualty who requires

mechanical ventilation will be returned to the battlefield? Probably not, with these two exceptions:

when perioperative ventilation is used for residual

anesthetic effects, and when mechanical ventilation

is used to support casualties of chemical war gases.

However, the mission of battlefield medicine is also

to save lives, and the use of mechanical ventilation

to accomplish this goal is without dispute.

When the number of mechanical ventilators is

limited, medical officers will be required to decide

which patients will receive them. This decision

may be based on several considerations. Probably

the most important, and least-biased, factors are (a)

the expected reversibility of the inciting injury and

(b) the predicted patient outcome. For example, the

casualty who develops ARDS will most likely require

at least 2 to 3 weeks of mechanical ventilatory support.

In addition, the mortality rate exceeds 40%.24 If this

patient receives a ventilator, several others with an

expected quick recovery may either sustain neurological injury or death if no respirator is available

for respiratory support. A second example is the

patient who develops multiple organ failure. If three

or more organ systems have failed for at least 3 days

in the ICU, the mortality exceeds 95% to 97%.44

Another factor that must be considered when a

limited number of mechanical ventilators is available is the medical officer’s experience and skill in

managing critically ill patients nonmechanically.

MECHANICAL VENTILATION AND COMBAT CASUALTIES

The medical officer working in the combat casualty environment must (a) understand the types of

pulmonary injuries that may occur and (b) be able

to evaluate the need for mechanical ventilatory

support. The decision to use a mechanical device

to assist ventilation is primarily based on the

patient’s inability to sustain sufficient gas exchange.

The most common reason for requiring positivepressure ventilation is refractory hypoxemia. Historically, this use of positive-pressure ventilation

dates back to 1938 for the treatment of pulmonary

edema.45

Military anesthesiologists and critical care specialists must understand the design of mechanical

ventilators, be able to choose the proper mode of

ventilation, and be able to select the appropriate

initial ventilatory settings. These required settings

include tidal volume, rate, peak gas flow, inspiratory-to-expiratory ratio, and the fractional concentration of oxygen. A further challenge to medical

officers is the lack of sophisticated monitoring for

casualties who are mechanically ventilated. Thus, a

good understanding of pulmonary physiology and

astute clinical-assessment skills are required to determine if the patient is appropriately ventilated

and oxygenated.

In contrast to the Vietnam War, where the capability for mechanical ventilation was very limited,

in future conflicts, state-of-the-art ventilators may

be available to save the lives of casualties who

would otherwise die. During the months following

the 2 August 1990 invasion of Kuwait by the Iraqi

army, the Department of Defense purchased many

types of mechanical ventilators, which were sent to

the Saudi Arabian theatre. An unexpected problem

arose, however: although many different kinds of

ventilators were available, most of them were unfamiliar to young physicians new to the military.

Additional problems relating to the provision of

mechanical ventilation in the field were the need for

oxygen, oxygen blenders, PEEP valves, and spirometers. The principal problem on the battlefield is the

availability of compressed oxygen. During the Vietnam War, oxygen was provided principally in cylinders, with replenishment by liquid oxygen. In

future conflicts, there are no plans for pipeline

oxygen supply in the land hospitals; however, there

should be an increased availability of liquid oxy-
Anesthesia and Perioperative Care of the Combat Casualty

686

gen. Use of oxygen sieves may become commonplace. The logistics of continual provision of filled

oxygen tanks is significant.

Indications for Mechanical Ventilation

A combat casualty’s need for mechanical ventilatory support generally falls under one of three categories: impaired oxygenation, inadequate ventilation (eg, the central ventilatory drive or the

functional integrity of the thoracic cage is impaired),

or an excessive amount and/or inefficiency of respiratory work. A number of clinical problems are

associated with more than one of these deficiencies

(Exhibit 25-3).

Several of these indications are self-explanatory;

however, a few merit specific comments. Oxygen

itself may be toxic to the pulmonary system when

administered in a high quantity. If a peripheral

oxygen saturation above 90% cannot be obtained

within a reasonable amount of time (< 12 h) by the use

of a face mask–nonrebreathing apparatus (FIO2 > .80),

then endotracheal intubation and mechanical ventilation should be instituted. Improved oxygenation

may be achieved by manipulation of the FIO2, mean

airway pressure, or the pattern of ventilation.

Although patients in cardiovascular collapse or

shock may not meet the arterial blood-gas criteria

for respiratory failure, supportive care for these

patients includes using mechanical ventilation to

reduce work demands placed on a patient with

inadequate cardiac output. Data from animal studies support this approach, as mortality was reduced

in the group of animals in shock that were supported with mechanical ventilation.39

Functional Design of Mechanical Ventilators

The type of ventilator is designated by its mechanism of cycling (ie, the event that terminates inspiration). There are three principal types of cycling:

pressure, volume, and time. Both volume and time

allow for a constant level of tidal volume. The tidal

volume varies during use of pressure-cycled ventilators whenever pulmonary compliance or airway

resistance change. An important component of the

ventilator’s design is its driving power (ie, what

empowers positive pressure); either compressed

gas (usually oxygen) or electrical power may be

used. Most modern ventilators, and all that are

designed for use in ICUs, are electrically powered,

have an internal battery for back-up power, and are

often controlled by a microprocessor. For medical

EXHIBIT 25-3

INDICATIONS FOR MECHANICAL

VENTILATION

Impaired Oxygenation

Direct thoracic trauma with resulting

pneumothorax

Hemothorax or pulmonary contusion

Hypovolemia and shock

Pulmonary edema

Progressive atelectasis

Pneumonia or aspiration pneumonitis

Adult respiratory distress syndrome

Impaired Ventilation

Postoperative state with residual anesthesia

Head injury

Chemical warfare injury

Quadriplegia from spinal cord trauma

Diaphragmatic injury

Fractured ribs or flail chest

Excessive Respiratory Work

Multiple trauma

Compensation for severe metabolic acidemia

Severe bronchospasm

Sepsis or multiple organ dysfunction

officers, this advantage is significant: it reduces the

amount of compressed oxygen that must be supplied to support field hospitals.

Simplistic, mechanical ventilators have only a

few components: a gas-controller device, blender,

humidifier, PEEP generator, and the circuit tubing.

The gas-controller device provides flow either on

demand, based on input from a sensor, or by continuous flow.

The limitations of specific ventilators are discussed later in this chapter.

Pressure Cycled

In pressure-cycled ventilators, inspiration ends

when a preset pressure is reached in the proximal

airway, as sensed by a manometer placed within the

ventilator circuit. The Bennett PR-2 is an example of

this type of ventilator, and is available in military

warehouses. It is one of the first kinds of ventilators
Acute Respiratory Failure and Ventilatory Management

687

sent to Saudi Arabia in 1990. However, a pressurecycled ventilator is used mainly in the patient who

is comatose, quadriplegic, or postoperative from general anesthesia; or who has a large leak around the

endotracheal tube and an anesthesiologist or clinician

who is experienced in reintubation is unavailable.

Many limitations discourage the use of the PR-2.

Volume Cycled

In volume-cycled ventilators, the inspiratory

phase ends when a preset volume is delivered to the

patient. This is the most common type of cycle

mechanism on modern ventilators and on all machines classified as “ICU ventilators.” Ventilators

of this type that were sent to the Persian Gulf War to

support U.S. and coalition forces include the Bear

33, Lifecare PLV-100 and PLV-102, Bennett MA-1,

and the Puritan-Bennett Companion. A safety feature of an appropriately set peak airway pressure

prevents excessive pressure in the airway if either

pulmonary compliance or airway resistance change

suddenly. When this “pop-off” pressure is reached,

the remainder of the tidal volume vents out of the

circuit and remains undelivered to the patient.

Volume cycling also has some limitations, including the need for a good seal around the endotracheal tube, and an inspiratory time that is unresponsive to the patients’ own respiratory pattern.

Time Cycled

In time-cycled ventilators, the inspiratory phase

ends when the selected time is reached. Ventilators

of this type include the Servo 900C (Siemens-Elema,

Solna, Sweden); the Evita (Dragerwerk, Bonn, Germany); and the Univent-750 (Impact Instrumentation, West Caldwell, N.J.). The Univent-750 was

designed as a transport ventilator and large quantities were sent to the Persian Gulf during Operation

Desert Storm. Similar to the volume-cycled ventilator, the time-cycled ventilator delivers a relatively

constant tidal volume. Tidal volume is determined

by either (a) the inspiratory time and the peak

inspiratory flow rate or (b) the minute ventilation

and the respiratory rate. For example, if the inspiratory time is 1 second, and the peak flow rate is 60 L/

minute, then the set tidal volume will be 1,000 mL.

The Evita, also a time-cycled ventilator, is an extremely flexible and capable ICU ventilator and

was supplied in large quantity to receiving hospitals in the U.S. Army Seventh Medical Command, in

Germany.

Flow Cycled

Pressure-support ventilation is generally viewed

as a mode of ventilation and may be performed on

either volume-cycled or time-cycled machines.

Nevertheless, the mechanism for termination of

inspiration (cycling) is unique in that flow to the

patient stops when the patient’s intrinsic inspiratory flow falls below a certain percentage of the

initial effort.

This topic is discussed more fully below.

Modes of Positive-Pressure Ventilation

There is no uniformly accepted terminology for

the different ventilatory modes. The application of

positive airway pressure can be divided according

to the timing during inspiration or exhalation, or

during both phases. When comparing the following modes of ventilation, one general concept should

be remembered: positive intrathoracic pressure may

contribute to decreased venous return and, therefore, to inadequate cardiac output. The degree to

which this complication becomes clinically significant depends on the duration and level of positive

airway pressure, whether any spontaneous (negative-pressure) breaths occur, and the patient’s preceding intravascular volume and cardiac status.

Inspiratory Positive Pressure

Controlled Mechanical Ventilation. In the controlled mechanical ventilation (CMV) mode, the

ventilator initiates positive-pressure inspiratory

cycles independent of the patient’s spontaneous

efforts. This method is indicated when the patient

is apneic secondary to heavy sedation, paralysis, or

coma; or when neuromuscular pathology, including quadriplegia, has occurred. A problem arises

when the patient tries to breathe spontaneously: the

patient may compete with the ventilator. The result

will be a patient who is at best uncomfortable, and

at worst subject to pulmonary overinflation and

barotrauma. All inspiratory cycles are positive

pressure, thus decreased venous return and decreased cardiac output are common. If the patient

does not initiate spontaneous efforts, then the entire work of breathing is provided by the ventilator.

This allows the patient to rest, but also may lead to

atrophy of the diaphragm and intercostal muscles.

Assist-Control Ventilation. Again, all inspiratory cycles are positive pressure with the AC mode

of ventilation. Any breaths taken above the rate set
Anesthesia and Perioperative Care of the Combat Casualty

688

by the physician must be triggered by a spontaneous effort. Competition between the patient and the

ventilator is therefore avoided, which reduces the

potential for barotrauma. The primary advantages of

AC ventilation are that (1) respiratory muscles rest

when the peak flow is high enough to decrease the

patient’s work of breathing and (2) the patient determines the PCO2 and the pH. Unfortunately, respiratory alkalosis is frequently observed in critically ill

patients. When AC ventilation is used, the medical

officer must remember that the set respiratory rate is

only a back-up if the patient’s spontaneous rate falls

below that frequency. The actual frequency of full

tidal-volume breaths will be determined by the

patient’s spontaneous rate or the set, mechanical

rate—whichever is the greater number.

Intermittent, Mandatory Ventilation. The IMV

mode allows unlimited, negative-pressure, spontaneous breaths between the delivered mechanical

breaths. As a result, this mode can be used across a

spectrum of minimal to complete ventilatory support, offering flexibility to the physician whose

patient load requires a large number of ventilators

or who is attempting to wean a patient from the

ventilator. IMV is indicated primarily during weaning. However, when the respiratory rate and tidal

volume are set high enough to provide most of the

patient’s minute ventilation requirement, the patient

can rest, and the work of breathing can be reduced.

The use of IMV has several advantages (Exhibit 25-4).

Synchronized, Intermittent, Mandatory Ventilation. The synchronized, intermittent, mandatory

ventilation (SIMV) mode was designed to improve

patient comfort and to prevent the stacking of

breaths (ie, repeated inhalations without full exhalation) that may lead to barotrauma. As with IMV,

the set rate is the minimum number of positivepressure breaths that the patient will receive regardless of his intrinsic central respiratory drive.

However, in SIMV, the patient’s spontaneous breathing and the ventilator are coordinated by means of

a circuit manometer, which detects the onset of a

spontaneous breath. Within a “window” during

which the ventilator should cycle (eg, every 6 s

when the set rate is 10 breaths per minute), if the

patient makes a spontaneous effort, the mechanical

breath will be triggered and superimposed at the

beginning of the patient’s respiratory cycle, rather

than randomly throughout. This timing should

help avoid barotrauma by synchronizing the ventilator-delivered breath with the inspiratory effort of

the patient. The only significant disadvantage of

the IMV or SIMV ventilatory mode is the potential

increase in work of breathing imposed by the demand valve incorporated into the ventilator.

Pressure Support Ventilation. The pressure support (PS) mode of ventilation is triggered by the

negative flow created by a patient’s spontaneous

breath. The initial use of this mode was the intermittent, positive-pressure breathing (IPPB) device.

The level of pressure support set by the physician

provides for positive airway pressure for the duration of spontaneous inspiration. Depending on the

type of ventilator employed, the pressure returns to

the end-expiratory pressure level when the inspiratory flow drops below a preset absolute rate or

percentage of the initial inspiratory flow rate. This

pressure augmentation results in reduced work of

breathing, which compensates for the increased

resistance from the endotracheal tube, ventilator

circuit, and mechanical demand valve (which may

be difficult to trigger). The total respiratory rate,

tidal volume, and length of inspiration remain under the patient’s control; the result is markedly

increased patient comfort. Pressure support is usually used in conjunction with SIMV, which provides

back-up ventilation in the event that patient-initiated efforts become inadequate (eg, excessive sedation, metabolic encephalopathy).

The disadvantages of pressure-support ventilation are that (1) the inspiratory cycle uses positive

pressure and (2) the delivered tidal volume varies

when changes in either airway resistance or pulmonary compliance occur.

The initial assist-pressure setting can be estimated at approximately one half the peak airway

pressure. An in-line expiratory spirometer should

be used to measure spontaneous breaths (5–7 mL/

kg exhaled tidal volume is a reasonable goal). None

of the ventilators that were sent to the Persian Gulf

War in 1990 had this capability.

EXHIBIT 25-4

ADVANTAGES OF INTERMITTENT,

MANDATORY VENTILATION

Distribution of ventilation is more normal

Physiological dead space is reduced

Detrimental effects on the cardiovascular system

are minimized

Some degree of respiratory muscle tone is

maintained

Respiratory alkalemia is minimized
Acute Respiratory Failure and Ventilatory Management

689

Inverse-Ratio Ventilation. As a patient’s respiratory gas exchange becomes progressively inadequate, increasing the inspiratory-to-expiratory ratio to greater than 1 may lead to significant

improvement (by elevating the mean airway pressure). The most likely mechanism for this improvement is an increase in lung volume resulting from

the recruitment of atelectatic alveoli through the

generation of intrinsic end expiratory pressure or

so-called “auto-PEEP.” Inverse-ratio ventilation

may be accomplished in the pressure or volume

control ventilatory modes. The pressure control

variety is achieved by maintaining the set pressure

limit for a fixed period of time. The volume control

mode of IRV results when the inspiratory flow rate

is reduced to the point whereby inspiratory time

exceeds expiratory time.39 Because this pattern of

ventilation is nonphysiological, sedation is usually

required for the patient.

High-Frequency Ventilation. High-frequency

ventilation can be provided in three modes: highfrequency, positive-pressure ventilation; high-frequency jet ventilation; and high-frequency oscillation. The advantages of high-frequency ventilation

are that the mean and peak airway pressures decrease, resulting in minimized risks of barotrauma

and cardiovascular impairment. The Food and Drug

Administration approves the use of high-frequency

ventilation in adults for only one condition:

bronchopleural fistula. The results of high-frequency ventilation in patients with ARDS have

been very disappointing, but there may be some use

for it in treating inhalation injury.11

Expiratory Positive Pressure

The application of positive pressure during exhalation, whether it occurs in the spontaneous or

the mechanically ventilated patient, is called expiratory distending pressure (EDP). The two principal methods of delivery are (1) CPAP, which uses

positive airway pressure throughout the spontaneous ventilatory cycle, and (2) PEEP, which uses

positive pressure during the exhalation fraction of

the cycle.

Expiratory distending pressure can be applied

via either a flow resistor or a threshold device

placed in the expiratory limb of the ventilatory

circuit. The result is that expiration is retarded,

prohibiting full exhalation, which, in effect, maintains alveolar distension. The flow resistor accomplishes this by changing the size of the orifice for

gas flow, whereas the threshold device allows no

expiratory flow until the pressure exceeds the set

valve pressure. The threshold device is preferred

because it can accommodate a sudden increase in

expiratory pressure (eg, during coughing) without

allowing a build-up of pressure in the ventilator

circuit.

Continuous, Positive Airway Pressure

Large, patient-initiated decreases in airway pressure are associated with increased work of breathing. CPAP may reduce the work of breathing by

giving an inspiratory assist, which leads to an almost passive inspiratory cycle. Continuous, positive airway pressure delivered via a face mask may

have a limited role in the treatment of combat casualties because of the frequent occurrence of

obtundation, which increases the risk for pulmonary aspiration of gastric contents. With proper

patient selection, however, continuous, positive airway pressure has certain advantages: (1) the maintenance of the patient’s ability to cough, (2) the

maintenance of the patient’s ability to warm and

humidify the inspiratory gases, and (3) the avoidance of complications associated with endotracheal

intubation. The primary disadvantage is gastric

distension (and the concomitant increased risk of

aspiration), which can be minimized by the placement of a nasogastric sump.

Clinical Use of Positive End-Expiratory Pressure

The use of PEEP merits specific attention not

only because this technique is popular but also

because the misconceptions regarding its use are

numerous. The only valid reason for using PEEP is

to increase lung volume—specifically, the FRC. The

FRC is composed of the residual volume and the

expiratory reserve volume. This lung capacity provides for a reservoir of oxygen-filled alveoli and

permits gas exchange between inspirations. The

FRC is frequently decreased following trauma or

surgery (Table 25-3).

In most patients, the length of the expiratory

cycle far exceeds the inspiratory. If alveoli are

permitted to close during the expiratory time, then

intrapulmonary shunting, resulting in hypoxemia,

may occur. This premise was used to defend the

“super” PEEP that was used during the 1970s, when

PEEP levels greater than 20 cm H2O were titrated

until the shunt fraction was decreased to the lowest

possible level.46 No prospective study has demonstrated improved patient outcome with the use of

these high levels of PEEP, leading most clinicians to

use PEEP in restricted amounts (eg, < 15 cm H2O).47
Anesthesia and Perioperative Care of the Combat Casualty

690

TABLE 25-3

CAUSES OF DECREASED FUNCTIONAL RESIDUAL CAPACITY

Cause Effect

Residual anesthetic Shifts the CO2 response curve or alters central respiratory control,

resulting in shallow tidal volume breathing

Abdominal distension Compresses the diaphragm and the lower pulmonary segments

Splinting of chest-wall Pain prevents deep breathing, which results in collapsed alveoli

movements secondary to thoracic pain

Excessive airway secretions Work of breathing increases as the airway is blocked

or obstruction

INITIATING MECHANICAL VENTILATION

The initial settings that are selected for mechanical support depend on the indication for which the

patient requires ventilatory support. Exhibit 25-5 is

a brief guide to setting the ventilator.

Tidal Volume and Respiratory Rate

The recommended initial settings for nonrespiratory failure–ventilatory support are a tidal volume

of 10 to 15 mL/kg and a respiratory rate of 7 to 10

breaths per minute, resulting in a minute ventilation of 70 to 150 mL/kg/min. The patient who is

comatose or who remains under the influence of

sedatives will generally be normocarbic at 80 mL/

kg/min. Higher rates should be used for the initial

setting when

• hypocapnic therapy is needed to treat increased intracranial pressure,

• a severe metabolic acidosis needs immediate compensation,

• a large amount of sodium bicarbonate has

been administered,

• a thermal burn has created hypermetabolism, or

• pulmonary vascular occlusion has caused

an increase in physiological dead space.

The selection of respiratory rate in the AC mode

only determines the minimum amount of ventilation that will be ensured if the patient loses his

respiratory drive. Thus, the selected setting should

provide for approximately 70% to 80% of the minute

ventilation required for the patient to maintain

normocarbia. To obtain the maximal benefit from

SIMV, once the patient is stable, the respiratory rate

should be set at the minimum amount necessary to

prevent respiratory acidosis.

Calculation of the tidal volume should be set

on the patient’s actual weight if the weight above

the estimated lean amount is the result of obesity.

Increased weight gain following fluid resuscitation does not necessitate increasing the tidal volume. Not all the set tidal volume will be delivered

to the patient’s alveoli because of dead space

(anatomical and artificial) and volume loss (from

the compliance of the ventilator circuit tubing).

When the patient reaches a peak airway pressure

of 40 to 60 cm H2O during ventilation, the average amount of volume lost is 3 to 4 mL/cm H2O

pressure.12

Fraction of Inspired Oxygen

Many of the ventilators sent to the Persian Gulf in

support of Operation Desert Storm in 1990 required

an additional, external oxygen blender to provide

oxygen in a relatively safe range (> room air [.21] and

< 1.0). All FIO2 settings—even on a sophisticated ICU

ventilator—should be confirmed by an oxygen analyzer that is placed within the inspiratory limb of the

patient’s breathing circuit. The initial setting for FIO2

will depend on whether pulmonary injury has occurred. In a postoperative patient who has sustained

only an extremity or lower-abdominal wound, a slight

increase in the FIO2 to .40 will usually suffice. If

significant pulmonary injury has occurred, then an

initial FIO2 of 1.0 should be selected. All attempts

should be made to use the lowest concentration of

oxygen that provides at least 90% oxygen saturation
Acute Respiratory Failure and Ventilatory Management

691

Volume-Cycled Ventilators

Apnea Spontaneous Ventilation

Control Mode Assist-Control/Synchronized, Intermittent,

Mandatory Ventilation

1. TV: 10–15 mL/kg 1. TV: 10–15 mL/kg

2. Not applicable 2. Sensitivity: –2 to –2.5 cm H2O

3. Respiratory rate: 3. Respiratory rate:

8–12 breaths per min AC: set default rate to 6–8 breaths per

min in case of apnea

SIMV: to rest the patient, ensure that

80% of breaths are mechanically

provided

4. Not applicable 4. PF: 3.5–4.0 • minute ventilation

5. Expiratory time should exceed inspiratory time by 2:1

6. Keep PAP < 30–40 cm H2O

7. Add PEEP in 2- to 4-cm H2O increments if hypoxemia

persists on FIO2 > 50%

8. Set PL at 15–20 cm H2O above PAP during a normal

breath or < 80 cm H2O

Pressure-Cycled Ventilators

1. TV: starting at 20 cm H2O, increase peak pressure until tidal volume is adequate by clinical examination

or arterial blood gas criteria

2. Respiratory rate: provides for a minimum amount if patient becomes apneic. Set to provide 70%–80% of

minute ventilation

3. FIO2: an in-line O2 analyzer is strongly recommended

4. Patient interaction: the spontaneously breathing patient may not tolerate this type of ventilator, necessitating either weaning or changing to a different mode of ventilation

Time-Cycled Ventilators

1. TV: set the inspiratory time and PF to provide the calculated tidal volume

2. Respiratory rate: ensures a minimal amount of ventilation

3. As the PF determines the TV, it is necessary to check the inspiratory-to-expiratory time ratio with each

rate change

EXHIBIT 25-5

MODES AND SETTINGS OF POSITIVE PRESSURE VENTILATION

AC: assist-control ventilation; FIO2: fraction of inspired oxygen; PAP: peak airway pressure; PEEP: positive end-expiratory

pressure; PF: peak flow; PL: pressure limit; SIMV: synchronized,intermittent, mandatory ventilation; TV: tidal volume

of the arterial hemoglobin. High oxygen concentrations are toxic to the lungs and may result in numerous complications. These include a deterioration in

ventilation–perfusion matching, absorption atelectasis, decreased mucociliary clearance, and ARDS.48

Decreasing the FIO2, utilizing a pulse oximeter as a

monitor, may be safely done in increments of 5% to

10% every 5 minutes.

Inspiratory Flow Rate

The peak inspiratory flow rate is particularly

important. If it is set too high, ventilation is

maldistributed throughout the lungs. If set too low,

the expiratory time may be shortened, creating a

problem for patients with obstructive airway disease. In all cases, the peak inspiratory flow rate
Anesthesia and Perioperative Care of the Combat Casualty

692

must exceed the patient’s intrinsic demand if further respiratory work by the patient is to be avoided.

A setting that is 3.5- to 4-fold greater than the

patient’s minute volume requirement is usually

adequate. When increasing the peak flow rate, the

physician will generally observe a rise in the peak

airway pressure. Occasionally, the peak airway

pressure will decrease, signifying that intrinsic (or

auto-) PEEP is occurring. This will resolve with

lengthening of the expiratory time.

Additional Settings

The remainder of the mechanical ventilator settings are often overlooked by medical officers but

will be set by a respiratory therapist. These include

the inspiratory-to-expiratory ratio, the selection of

an inspiratory waveform (square, ramp, sine), and

a variety of alarms. The most important alarm,

which is accompanied by a release mechanism, is

the peak airway pressure. Initially, this should be

set for approximately 15 to 20 cm H2O higher than

the peak pressure measured during unlabored, mechanical breathing. These additional settings are

important for the intensivist when a patient is particularly difficult to ventilate.

Stabilizing the Patient in Acute Respiratory

Failure

The approach to initiating mechanical support in

the patient in acute respiratory failure differs from

the previous discussion. The initial settings recommended above are merely a guideline for initiating

mechanical support. As a result of either hypermetabolism or increased dead-space ventilation, a combat casualty’s minute ventilation requirement may

be as high as 25 to 30 L/min. Respiratory muscle

fatigue appears to be a common component of acute

respiratory failure regardless of the etiology.49 The

initial goal is to ensure a good quality of rest and

recovery. Using a constant tidal volume of 10 to

15 mL/kg, the respiratory rate should be increased

until the patient is comfortable and rested. When

these high levels of mechanical support are required, bedside supervision by an intensivist is

necessary to avoid (a) excessive elevation of airway

pressure and (b) air-trapping, which results from an

inadequate expiratory time. Although the AC mode

may allow the greatest decrease in the patient’s

work of breathing, a very tachypneic or anxious

patient may cause excessive triggering and stacking

of ventilations. Occasionally, the patient may need

to be sedated and paralyzed so that hemodynamic

compromise can be minimized and the elimination

of carbon dioxide can be improved.

Patients who do not respond initially to treatment for sepsis or shock should be considered for

early intubation and mechanical ventilatory support. Considerable oxygen can be consumed by the

diaphragm alone (as much as 30%–40% of the body’s

total amount) in the state of shock or acute respiratory failure.50

Following a period of stabilization, a progressive

amount of work should be assumed by the patient

to prevent atrophy and promote conditioning.51

MONITORING THE EFFECTIVENESS OF VENTILATION AND OXYGENATION

Monitors used in patients with acute respiratory

failure may be characterized as invasive or

noninvasive, and intermittent or continuous. A

monitor may either follow only the progression of

disease or give concomitant information regarding

the effect of therapy.

Oxygen Concentration

The FIO2 delivered to the patient is one of the

most important and easiest parameters to measure.

Once the FIO2 is known, other indices—all of which

serve as markers for the severity of pulmonary

dysfunction—can be calculated:

• the difference between the partial pressure

of oxygen within the alveoli and that present

within the arterial blood (PAO2 – PaO2); normal is 5 to 10 mm Hg;

• the ratio of arterial to alveolar partial pressure of oxygen (PaO2/PAO2); normal is 0.75; and

• the ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2/

FIO2); normal is 250 mm Hg.

Pulse Oximetry

The pulse oximeter is a continuous monitor that

detects the percentage of total hemoglobin saturated with oxygen. This is achieved by using a

photoelectric tube to measure the amount of light

transmitted at two different wavelengths. Only the

arterial component of the blood in the tissue is

analyzed. This is done by simultaneously measuring pulsatile flow and subtracting the background

absorption, which is the nonpulsatile venous and

capillary blood. Because of a different stereochemistry of hemoglobin molecules, saturated and un-
Acute Respiratory Failure and Ventilatory Management

693

0 50 100 150

0

20

40

60

80

100

Oxygen Pressure (mm Hg)

Oxyhemoglobin Saturation (%)

Fig. 25-2. The sigmoid shape of the oxyhemoglobin dissociation curve, with its nonlinear relation between the

partial pressure of oxygen dissolved in blood and the

percentage of oxygen saturation of hemoglobin, must be

borne in mind when interpreting blood gas data. The

shape and position of the curve can be estimated in terms

of these three points, which fix the relation between

partial pressure and saturation: (a) the oxygen pressure

at which hemoglobin is 50% saturated (P50), (b) the oxygen pressure of mixed venous blood, which is normally

75% saturated (SmvO2), and (c) the partial pressure at

which hemoglobin is 90% saturated.

saturated hemoglobin display unique absorption

spectrums. To use this information clinically, the

physician must know the three key points on the

oxyhemoglobin dissociation curve (Figure 25-2):

a. the P50, the PO2 at which 50% of the hemoglobin molecules are saturated, which normally occurs at 27 mm Hg;

b. the mixed venous saturation (SmvO2) (75%),

corresponding to a PO2 of 35 to 40 mm Hg;

and

c. the “knee” of the curve at 90% saturation

of hemoglobin molecules, at a PO2 of approximately 60 mm Hg.

This technology has several limitations: pulse

oximetry (a) does not compute carboxyhemoglobin

or methemoglobin as desaturated hemoglobin, (b)

is inaccurate in instances of severe anemia (< 7 g/

dL), and (c) does not measure venous oxygen saturation because venous blood is only slightly pulsatile. The latter situation may occur when large

amounts of PEEP are applied. One important point

is that the patient’s PO2 may decrease from 400 to

100 mm Hg, representing a significant change in

pulmonary function, yet the pulse oximeter saturation display does not change.

The Persian Gulf War was the first conflict in

which pulse oximeters were widely available for

patient monitoring. Oximeters were present at all

anesthetizing locations, within the ICUs, and in the

emergency departments.

Gas-Exchange Indices

Partial Pressure of Arterial Oxygen

Factors other than the gas-exchange capability

and efficiency of the lung may affect the PaO2. Two

clinical situations that exemplify this point are (1)

shock, during which the venous PO2 is markedly

reduced, and (2) a state of increased VO2. The

desaturating effect of venous hypoxemia is exacerbated in the presence of lung pathology, contributing to intrapulmonary shunting. Hence, when hypoxemia (low PO2) occurs, it is not a correct

assumption that the patient’s clinical problem is

one of strictly pulmonary pathology. Conversely, if

the PO2 is completely normal for a given FIO2, the

lungs are assumed to be functioning normally. The

PO2, when measured by an arterial blood-gas determination, is the accepted standard for measuring

oxygenation.

Arterial blood gases as a monitor of oxygenation

have the limitation of reflecting the clinical state at

only one moment. Furthermore, the PaO2 measures

only the oxygen dissolved in the blood, which is

only a small fraction of the total amount of oxygen

delivered to the tissues. Most of the arterial oxygen

content is that portion of oxygen bound to hemoglobin. However, the PaO2 is the major determinant of

the position on the oxygen–hemoglobin dissociation curve and thus determines the arterial hemoglobin oxygen saturation.

Alveolar–Arterial Oxygen Tension Difference

The difference between the partial pressure of

oxygen in the alveoli and in the arteries (PAO2 –

PaO2) is a specific indicator of pulmonary pathology, but this index has a significant practical limitation: the clinician must know the FIO2. Multiple

determinations of the calculated value for PAO2 –

PaO2 are accurate predictors of pulmonary injury

only when the FIO2 has remained constant. PAO2 –

PaO2 is calculated using the following equation:

PAO2 – PaO2 = FIO2 (PB – PH2O) – PCO2/R.Q.

where PB represents barometric pressure (760 mm

Hg at sea level); PH2O represents partial pressure of

fully saturated water vapor (47 mm Hg); and R.Q.

represents the respiratory quotient, assumed to be

0.8 with a normal diet. The normal value for PAO2 –

a

b

c
Anesthesia and Perioperative Care of the Combat Casualty

694

PaO2 is less than 10 mm Hg for a healthy, young

adult.

The Ratio of Arterial to Alveolar Oxygen Tension

The arterial-to-alveolar oxygen tension ratio

(PaO2/PAO2) remains more stable with alteration in

the FIO2, and this calculation can be employed to

predict the expected PaO2 when the FIO2 is altered.

The normal value is 0.75.

The Ratio of Arterial Oxygen to Inspired Oxygen

The arterial-to-inspired oxygen ratio (PaO2/FIO2)

is the simplest index to calculate, as it does not

require use of the alveolar gas equation. The normal value is greater than 250 mm Hg.

Right-to-Left Shunting

Right-to-left intrapulmonary shunting of blood

leads most of the hypoxemia seen with severe respiratory failure. The shunt equation applicable to

severe respiratory failure is

Qs/Qt = CcO2 – CaO2/CcO2 – CvO2

where Qs represents the flow to the shunt, Qt represents the total pulmonary blood flow, and CcO2

represents the oxygen content of pulmonary capillary blood, which equals (1.34 mL O2/g Hb) •

(Hb g/dL) • (% SO2). The pulmonary capillary

blood is assumed to be fully saturated (SO2 = 100%).

CaO2 represents the arterial oxygen content and

CvO2 represents the pulmonary venous oxygen content whose hemoglobin oxygen saturations can be

directly measured. This equation discounts the

small contribution of dissolved oxygen in computing the various oxygen contents.

If FIO2 = 1.0, then the following simplified shunt

equation may be used:

Qs/Qt = P(A – a)O2/20

Monitoring Mechanical Ventilation

The importance of bedside patient observation

cannot be overemphasized. Much information is

gained by attentively watching the patient’s spontaneous ventilatory efforts and use and coordination of the thoracoabdominal muscles of inspiration.

In addition to the more-specific pulmonary pathologies, tachypnea is an early sign of shock or sepsis.

Airway Pressures

The peak and plateau airway pressures are monitored in all patients in respiratory failure who are

supported by mechanical ventilation. From these

measurements the dynamic and static compliance

may be calculated as follows:

Cd = change in volume/(PAP – PEEP)

Cs = change in volume/(PLP – PEEP)

where Cd represents dynamic compliance, Cs represents static compliance, change in volume represents

ventilator tidal volume, PAP represents peak airway pressure, PEEP represents positive end-expiratory pressure, and PLP represents plateau pressure. Actual tidal volume should be corrected by

subtraction of the volume lost for circuit expansion

(3–4 mL/cm H2O peak airway pressure).

A single, discrete value cannot be given be given

for the dynamic compliance, which is flow dependent. Static compliance has the range 75 to 125 mL/

cm H2O. The normal values are position dependent, and, for supine measurements, the normal

value should be reduced approximately 30%.

The measurement of dynamic compliance is

affected by the airway resistance, the compliance

of the pulmonary parenchyma, and the compliance of the chest wall. The difference in peak and

plateau pressures (normal = < 10 cm H2O) indicates

the difference between these two compliances

and is independent of airway resistance.52 If this

difference is large, then therapeutic intervention

should be directed toward minimizing or eliminating the contributing factors (Exhibit 25-6).

Bronchospasm is a common cause of increased airway resistance during mechanical ventilation. StanEXHIBIT 25-6

FACTORS CONTRIBUTING TO

INCREASED AIRWAY RESISTANCE

Airway secretions

Kinked endotracheal tube

Narrow internal diameter of the endotracheal tube

Condensed water in the ventilator tubing

Bronchospasm
Acute Respiratory Failure and Ventilatory Management

695

dard medical therapy includes inhaled beta agonists, inhaled anticholinergic agents, theophylline,

and steroids.

If both the peak and plateau airway pressures

are elevated and there is minimal difference between the dynamic and static compliances, then the

compliance of either the pulmonary parenchyma or

the chest wall has been reduced. Most commonly,

this is the result of pulmonary injury (Exhibit

25-7). All medical officers caring for patients on

mechanical ventilation must remember that the

peak airway pressure is not infrequently elevated

as a result of the selection of ventilatory settings (peak inspiratory flow, tidal volume, and respiratory rate), an example of iatrogenic noncompliance.

Capnography

Whenever possible, end-tidal carbon dioxide

(ETCO2) monitoring (capnography) should be used

in every patient on mechanical ventilation. The

initial widespread clinical use of capnography was

to confirm the correct placement of an endotracheal

tube. If direct visualization and placement of an

endotracheal tube between the vocal cords is not

achieved, capnography is the only other absolute

confirmation of correct placement. A malpositioned

endotracheal tube is a greater problem in a critically

ill patient in the ICU than in an anesthetized, paralyzed patient in the operating room. Patients in the

ICU are obviously intubated for longer periods of

time, are more mobile, more interactive, often more

agitated, and are not continuously observed at the

bedside, compared to patients in the operating room.

Self-extubation is a recognized complication in all

ICUs, with an estimated occurrence of 11% to 13%.53

In addition, because of patient movement and respiratory therapies, disconnections in the airway

circuitry (ventilator tubing, humidifier, nebulizer)

occur frequently. Capnography provides immediate detection of airway obstruction, extubation, or

ventilator disconnection. The presence of a regularly occurring exhaled carbon dioxide waveform

confirms the continued presence of an intratracheal

tube. The use of pulse oximetry is not a replacement

for monitoring these events, as pulmonary oxygen

reserve may allow sufficient gas exchange for several minutes.

An idealized normal capnogram is shown in Figure 25-3. In contrast to pulse oximetry, monitoring

of exhaled carbon dioxide can provide more information than just the ETCO2 (recorded in mm Hg or

% CO2). From the shape of the waveform, we can

infer several observations such as the adequacy of

alveolar emptying and the magnitude of pulmonary dead space. A well-defined plateau tells us

that alveolar emptying is adequate and pulmonary

dead space is minimal; therefore, ETCO2 closely

matches PaCO2.

The difference between PaCO2 and ETCO2 is normally 4 to 7 mm Hg for most monitors currently

available. An increase in this gradient in a patient

on mechanical ventilation suggests the further development of physiological dead space. Exhibit 25-8

lists frequent clinical causes of increased dead space

ventilation.

EXHIBIT 25-7

CLINICAL CAUSES OF REDUCED

PULMONARY COMPLIANCE

Pulmonary edema

Pneumonia

Atelectasis

Pulmonary fibrosis

Pneumothorax or hemothorax

Pulmonary aspiration

Chemical pneumonitis

4. Inspiratory

downstroke

2. Expiratory

upstroke

Time

Fig. 25-3. Idealized capnogram waveform, with time

plotted on the x axis and exhaled carbon dioxide concentration on the y axis. The numbered segments indicate the

four phases of the ventilatory cycle. Adapted with permission from Benumof JL. Anesthesia for Thoracic Surgery.

2nd ed. Philadelphia, Pa: WB Saunders; 1995: 244. Exhaled CO2 Concentration

1. Inspiratory

baseline

3. Alveolar

plateau
Anesthesia and Perioperative Care of the Combat Casualty

696

Analysis of the carbon dioxide waveform also

provides information regarding bronchospasm (the

slope of the ascending segment) and the competency of the ventilator expiratory valve (baseline

rebreathing of CO2 > 2–4 mm Hg). One study54

indicated that a rise or reappearance of exhaled carbon dioxide is one of the first indicators of the return

of spontaneous circulation following a cardiopulmonary arrest. Additional studies have demonstrated

that ETCO2 monitoring may be a good indicator of

both the adequacy of pulmonary blood flow and

cardiac output, and also a good prognostic indicator

of the success of cardiopulmonary resuscitation.55

Exhaled Volume Monitoring (Spirometry)

It is crucial that exhaled tidal or minute volume

be monitored while mechanical ventilation is used.

Several of the ventilators that were sent to the Persian Gulf War—including the Univent 750, Bear 33,

Lifecare PLV-100 and Lifecare PLV-102—did not

have built-in exhaled volume monitoring. Monitoring of exhaled volume is particularly important

when using either a pressure-cycled or a time-cycled

mechanical ventilator. The use of these ventilators

does not ensure the maintenance of a constant minute

ventilation and a stable PCO2 level. Even during the

use of volume-cycled ventilation, measurement of

exhaled volume serves as an additional monitor

warning of a disconnection, a malfunctioning inspiratory or expiratory valve, an endotracheal or

tracheostomy cuff leak, or a marked change in the

pulmonary compliance (eg, pneumothorax).

EXHIBIT 25-8

FACTORS CONTRIBUTING TO

INCREASED DEAD SPACE

Pulmonary

Bronchospasm

Chronic obstructive pulmonary disease

Excessive positive end-expiratory pressure

Circulatory

Hypovolemia

Hypotension

Reduced cardiac output

Pulmonary embolism (thrombus, air, fat)

Clinical Examination of the Patient–Ventilator Unit

The clinical examination of the patient receiving

mechanical ventilation (ie, the patient–ventilator

unit) is the most important “monitor” of all. The first

observation to make is determining whether the patient is ventilating spontaneously. If the patient

demonstrates a lack of ventilatory effort, it usually

reflects one or more of the criteria discussed in Exhibit

25-9. If the patient is making spontaneous ventilatory

efforts, then ensure that the ventilator is not in the

CMV mode, as this setting does not allow for ventilation beyond that designated by the set rate.

It is equally important to evaluate how well the

mechanical support is meeting the patient’s ventilatory requirements. If purpose of mechanical ventilation is to better meet the patient’s ventilation and

oxygenation needs, then allowing the patient to

perform an excessive amount of the work of breathing defeats the purpose of mechanical support. The

amount of minute ventilation required to maintain

normocarbia can provide useful information as to

the amount of dead space ventilation and the overall metabolic state in the setting of trauma and

serious infection.

The level of peak airway pressure is a major risk

factor for the development of barotrauma. For this

reason, should the airway pressures be increased or

noted to be rising, it is prudent to evaluate the patient

for reversible causes of airway pressure elevation.

Lastly, should the patient demonstrate agitation

while receiving mechanical ventilation, one should

always first assume that the problem rests not with the

patient, but rather with the ventilator itself or the

manner in which it is being employed. By fully

evaluating the ventilator and assuring that there are

no malfunctions or inappropriate ventilatory settings,

the clinician can avoid a potential catastrophe.

Oxygen Delivery

The gas exchange capability of the lung, as assessed by the PaO2, AaDO2, or other indices, is only

one of the components that determines DO2 to tissues. The two other major components are the level

of hemoglobin and the cardiac output. (The comments in this chapter are limited to respiratory

insufficiency; the reader can find a more detailed

discussion in Chapter 24, The Syndromes of Systemic Inflammatory Response and Multiple Organ

Dysfunction.) However, a number of studies56–59

give credence to the importance of the calculation of

both DO2 and VO2 by use of a pulmonary artery
Acute Respiratory Failure and Ventilatory Management

697

EXHIBIT 25-9

CRITERIA FOR OPTIMAL VENTILATOR USE

1. Is the patient ventilating spontaneously?

If NO, then

a. The settings (TV, rate) for mechanical support exceed the patient’s requirement.

b. The patient’s apneic threshold has been altered (eg, narcotics, benzodiazepines).

c. pH compensation is needed for a severe metabolic alkalosis.

d. The patient does not have an intact central ventilatory drive (eg, due to a closed head injury or coma).

e. The patient’s thoracic or diaphragmatic muscular function is inadequate (eg, due to nerve agents,

extreme fatigue, malnutrition).

If YES, then

a. Change from control mode to either AC or SIMV, and

b. Evaluate how hard the patient is working while maintaining this spontaneous ventilation (eg, respiratory rate, diaphoresis, pulse, mental status).

2. What is the minute ventilation requirement?

a. The requirement will vary frequently in the same patient based on the physical demands and the

therapies being performed.

b. The daily trend in mechanical ventilation provides information as to overall patient status in sepsis

and trauma.

3. Is the peak airway pressure too high (ie, progressively increasing or > 50 cm H2O)?

If YES, then

a. Evaluate dynamic (TV/PAP – PEEP) and static (TV/plateau – PEEP) compliances.

b. Evaluate whether bronchospasm or secretions are causing increased airway resistance.

4. Is the patient fighting the ventilator?

If YES, then evaluate for the following:

a. Secretions and the need for suctioning,

b. Bronchospasm, and

c. Stacking of breaths or “auto-PEEP” because of too short an expiratory time or too high a sensitivity

setting.

REMEMBER: the patient is “fighting” for his life. Do not sedate and paralyze the patient until you are confident that

the ventilator is not malfunctioning and that the settings chosen are appropriate for the patient’s needs.

TV: tidal volume; AC: assist control; SIMV: synchronized, intermittent, mandatory ventilation; PAP: peak airway pressure;

PEEP: positive end-expiratory pressure

catheter. Several clinical states including sepsis

and ARDS are characterized by what appears to be

a pathological oxygen-supply dependency. Systemic oxygen need may reach levels as high as 21

mL/kg/min.60 (Arterial and mixed-venous oxygen

contents and the cardiac index must be measured

simultaneously to allow these calculations.)

The usefulness of augmenting cardiac output has

been difficult to demonstrate in several clinical trials. In both the surgical setting and the setting of

myocardial infarction,61pushing cardiac output with

inotropic drugs has not been associated with improved outcome. These studies are difficult to

perform, since critically ill patients are sometimes

hard to match—but meta-analysis and further clinical trials will elucidate the true effects of artifically

increasing oxygen delivery. At this time, the question remains only partially answered and is the

source of considerable controversy among practitioners across the country.62,63
Anesthesia and Perioperative Care of the Combat Casualty

698

offers information pertinent to the patient’s intravascular volume status, the presence of congestive heart failure, or the possible occurrence of a

pulmonary embolism. The latter should be suspected when a pleura-based, wedge-shaped infiltrate (Hampton’s hump) or regional oligemia

(Westermark’s sign) are seen on a chest roentgenogram.

Mechanically Ventilated Patients. Patients

who require mechanical ventilation may benefit

from additional radiographic monitoring for potential complications. A daily chest X-ray examination is a good method to use for confirming a safe

location for an endotracheal tube. Although other

monitors (such as capnography) exist to confirm

intratracheal placement, a chest X-ray examination

will reveal the exact location of the cuff and the tip

of the endotracheal tube. To prevent either

intubation of the right main bronchus or accidental

extubation, the optimal distance from the carina to

the tip of the endotracheal tube is 3 to 7 cm. The

carina is used as a reference point because the

relationship of the endotracheal tube tip to the

clavicle changes, depending on the angle at which

the film was exposed. Tracheostomy tubes are

much more secure, and less frequent radiological

monitoring is required.

Mechanical ventilation may be associated with

barotrauma. This is more common when peak airway pressures exceeding 40 to 50 cm H2O have been

employed. Barotrauma may take several forms

including pneumothorax, pneumomediastinum,

pneumoperitoneum; or subcutaneous emphysema

of the chest wall, neck, or even the eyes. Patients in

respiratory failure who require high levels of ventilatory support, particularly once evidence of

barotrauma is present, need frequent, routine chest

X-ray examinations, as well as an additional one

whenever a clinical deterioration in either hemodynamic or respiratory status occurs. A small

pneumothorax in a patient being supported with

positive-pressure ventilation may at any time become a tension pneumothorax with the accompanying hemodynamic compromise.

Hemodynamic Monitoring

Although arterial, central venous, and pulmonary artery–catheter monitoring are important in

monitoring the critically ill patient, a full discussion

of hemodynamic monitoring is beyond the scope of

this chapter. Further information may be found in

Chapter 5, Physiological Monitoring.

Chest Radiography

Daily chest X-ray examinations are an accepted

ICU monitor for patients in respiratory failure. Several studies have validated the importance of daily

chest X-ray examinations in critically ill unstable or

mechanically ventilated patients: approximately

14% to 15% of chest X-ray examinations demonstrate unexpected findings that lead to a change in

management.64,65

Most chest X-ray examinations taken of critically

ill patients are made by a portable device at the

bedside. These films are taken from an anteriorposterior rather than the standard posteroanterior

orientation. This is important for several reasons.

The distance from the X-ray beam to the intrathoracic structures is not constant, and objects that are

far from the film (cardiac silhouette) are magnified.

Critically ill patients, particularly those in respiratory failure, are often tachypneic, and obtaining an

end-inspiratory chest film is difficult because they

cannot hold their breath. It should be remembered

that a chest X-ray examination cannot properly

evaluate upper-airway obstruction; however, careful attention not infrequently reveals tracheal abnormalities. One example of this is tracheal or left

main bronchus deviation when a traumatic aortic

dissection occurs. The information that can be

obtained from a chest X-ray examination depends

on the respiratory status of the casualty: whether

the patient’s ventilations are spontaneous or mechanically assisted.

Spontaneously Ventilating Patients. Chest radiography is used to evaluate the patient for pulmonary parenchymal injury. The presence of a radiological density may represent collapse of alveoli

(eg, atelectasis); or alveolar consolidation from water

(pulmonary edema), blood (aspiration or bronchoalveolar hemorrhage); or infected secretions (pneumonia). These fluids are indistinguishable radiologically, and clinical examination or other

diagnostic tests must be conducted to discern the

actual cause. The chest X-ray examination may also

detect pathology in the pleural space (eg, pneumothorax, hemothorax, or effusion). Frequently, chest

X-ray examinations done in this patient population

are performed in the supine position, and a

pneumothorax may be missed. One helpful radiological sign is the “deep sulcus sign,” a clear

costophrenic angle that often extends well below

the normal location for the diaphragm.

Additionally, radiological assessment of the

heart, great vessels, and pulmonary vasculature
Acute Respiratory Failure and Ventilatory Management

699

WEANING FROM MECHANICAL VENTILATION

EXHIBIT 25-10

CRITERIA FOR WEANING FROM

VENTILATORS

Respiratory or Metabolic Demand or Both

Respiratory rate < 25

Minute ventilation < 10 L/min

Dead space ventilation < 30%–40% of total

ventilation

Oxygenation

PaO2 > 60 mm Hg on FIO2 < 50%

PEEP < 5 cm H2O

Intrapulmonary shunt < 30%

Adequate hemoglobin concentration (7–10 g/dL)

Respiratory Muscle Strength

Tidal volume > 5 mL/kg

Vital capacity > 10 mL/kg

Negative inspiratory force > –30 cm H2O

Maximal voluntary ventilation > 2-fold the

resting minute ventilation

PaO2: partial pressure of arterial oxygen; PEEP: positive

end-expiratory pressure

Weaning the patient from mechanical ventilation

refers to shifting to partial ventilatory support while

observing the patient’s response to the increased

work of breathing associated with spontaneous ventilation. Weaning is frequently unnecessary in patients who are mechanically supported for a brief

period of time following surgery or another medical illness and who have not suffered from malnutrition. These patients should not have developed

respiratory muscle fatigue.

Discontinuation of mechanical ventilation should

be considered only if the underlying cause of the

respiratory failure (eg, treated pneumonia, resolved

sepsis, arousal from coma) has been reversed.

Discontinuation is likely to prove possible only if

the following preconditions have been met:

• the central respiratory drive is intact, ensuring normocarbia;

• muscular strength is adequate to maintain

a clear airway and provide for full spontaneous breathing;

• the patient is hemodynamically stable (ie,

shock is resolved, intravascular volume

restored); and

• carbon dioxide production is not elevated.

Medical officers, however, must consider not

only the casualty’s condition but also the need for

aeromedical evacuation to a higher echelon of care.

The U.S. Air Force is reluctant to evacuate casualties

on ventilators and, in fact, refused to do so during

the Persian Gulf War. (See Chapter 27, Military

Medical Evacuation, for a more complete discussion of this subject.)

Many criteria have been published to evaluate a

patient’s ability to be successfully weaned from

mechanical ventilatory support (Exhibit 25-10).

Some of these criteria are subjective and thus require good clinical acumen as to the physiological

capability of the patient. Even objective criteria that

can be measured and quantified have been questioned, as there are patients who do successfully

wean from mechanical support despite their not

meeting the weaning criteria.66,67 In addition, certain of the quantitative measurements are frequently

not performed properly and thus may give false

information. Nevertheless, combining criteria into

a decision tree (Figure 25-4) is usually helpful in

deciding if and when to wean. Application of the

decision tree presupposes that the patient is not

sedated to the point where the ventilatory drive is

blunted.

Several of these indicators (negative inspiratory

force, minute ventilation, and maximum voluntary

ventilation) were evaluated in one study.68 If the

minute ventilation was less than 10 L, then the

maximum voluntary ventilation was 2-fold greater

than the minute volume, and the negative inspiratory force was greater than –30 cm H2O. All patients were successfully extubated in this study.

These parameters are probably of greater use in

short-term ventilator use than they are in prolonged,

when the clinical judgment of the physician is as

valid as the measured criteria.

Patients who required prolonged (> 30 d) mechanical ventilation have been shown to have a

hospital mortality identical to patients who required

only short-term mechanical ventilation.69 Thus,

these patients deserve a well-conceived plan for the

goal of successful extubation and separation from

mechanical ventilatory support.
Anesthesia and Perioperative Care of the Combat Casualty

700

Fig. 25-4. Decision tree for weaning from mechanical ventilation.

Is the Disease

ProcessThat Led to

Respiratory Failure

Resolved or Improved?

Evaluate conventional weaning criteria:

1. PaO2 > 60 mm Hg with FIO2 < 50%

2. PAO2 – PaO2 < 250 mm Hg

3. PaO2/FIO2 > 200

4. Vital capacity > 10 mL/kg body weight

5. Negative inspiratory effort < –30 cm H2O

6. Minute ventilation < 10 L/min

7. Respiratory rate < 35/min

8. Respiratory rate ÷ tidal volume (in liters) < 100

Weaning from mechanical

support is likely to fail

Are

Abnormalities

Corrected?

Correct abnormalities:

1. Nutrition

2. Electrolytes

3. Acid–base balance

4. Congestive heart failure

5. Infection

Patient is likely to

wean and extubate rapidly

Are

All Criteria

Met?

Weaning from mechanical

support is likely to fail

Yes

Yes

Yes

No

No

No
Acute Respiratory Failure and Ventilatory Management

701

The first step in weaning a patient who has been

dependent on mechanical ventilatory support is to

optimize the patient’s general status (Exhibit 25-11).

This may seem obvious, but it is not fully appreciated and is frequently overlooked completely—

especially when too much attention is directed toward purely respiratory indices. Even if the patient

demonstrates no respiratory distress, it is unwise to

wean a patient who appears to be in any form of

shock. By definition, the term “shock” means that

the supply of blood and nutrients (oxygen and

glucose) to organs or tissues has not met the demand. If such a patient were required to sustain full

spontaneous ventilation, the increase in oxygen

demand could worsen the balance between systemic oxygen delivery and systemic oxygen need.

For example, in sepsis, oxygen utilization by the

diaphragm can be very high and, in fact, can constitute nearly 30% to 40% of the body’s total VO2.

50

Several clinical conditions may lead to an elevated production of carbon dioxide, necessitating

a higher minute ventilation to maintain normocarbia. Patients who are febrile, agitated, in pain, or

who have suffered traumatic injuries, thermal burns,

or seizures produce increased carbon dioxide. Excessive carbon dioxide production may also arise

iatrogenically as a result of excessive carbohydrate

administration. (For a more complete discussion,

see Chapter 23, Metabolic Derangements and Nutritional Support.)

It is often impossible to determine the exact cause

of a patient’s failure to wean, but recent discussion

has focused on respiratory muscle fatigue and disEXHIBIT 25-11

FACTORS THAT MAY PREVENT DISCONTINUATION OF MECHANICAL VENTILATION

The patient must not be malnourished. Diaphragmatic muscle loss is nearly linearly related to the degree of

malnutrition.1,2

Significant acid–base and electrolyte abnormalities must be corrected, including metabolic alkalosis that

demands hypoventilation to normalize the serum pH.

Hypophosphatemia may also contribute to respiratory muscular weakness.

Left-ventricular failure leading to reduced pulmonary compliance may be an occult cause of persistent failure

to wean from mechanical support.

Airway secretions may be a significant problem to the patient after extubation, during which time small-airway

obstruction leads to atelectasis and bronchospasm.

Sources: (1) Bell RM, Bynoe RP. Nutrition and respiration. Prob Crit Care. 1987;1(3):413–434. (2) Lewis MI, Belman MJ.

Nutrition and the respiratory muscles. Clin Chest Med. 1988;9(2):337–348.

use atrophy as two important causes. It may be

clinically impossible to distinguish between these

two causes. Respiratory muscle fatigue has been

suspected clinically for some time and electromyographic evidence supports this concern.70 The clinician must remain alert to mechanical factors that

exacerbate rather than aid respiratory muscle fatigue. Most intensivists know that increased airway resistance results from using a small endotracheal tube (< 7.0 mm internal diameter). A

tracheostomy, by increasing the diameter and shortening the length of the airway, may reduce the

resistance. Occasional patients may wean best by

simply proceeding to extubation, totally eliminating the resistance of the artificial airway. (This is

becoming less necessary as advanced mechanical

ventilators with multiple ventilatory modes are

developed.)

The three principal weaning modalities are (1) a

progressive reduction of mechanical support

through the use of IMV, (2) T-piece trials, whereby

the patient is disconnected from the ventilator and

attached to a T-piece for progressively longer intervals, and (3) pressure-support weaning. The literature does not support the superiority of any one

method.67

T-piece trials should be initiated in 5-minute

intervals, with the physician or nurse at the bedside

to evaluate any significant changes in the patient’s

respiratory rate, pulse, or subjective complaints of

excessive work. T-piece trials use intermittent periods of vigorous breathing intended to increase the

patient’s respiratory endurance. Rest periods are
Anesthesia and Perioperative Care of the Combat Casualty

702

important to the success of this method. The definition of quality respiratory rest (ie, the respiratory

muscles are resting) has been clouded by recent

studies showing significant amounts of respiratory

work with AC ventilation. In addition, the optimal

rest time between periods of T-piece work has not

been answered in the literature. Our practice has

been to allow for a minimum of one hour between

exercise periods and rest the patient with full ventilatory support overnight.

SIMV is another ventilatory strategy commonly

used in weaning. Quite simply, the number of

mechanical breaths per minute provided to the patient are gradually reduced over several days to

weeks. As the number of mechanical breaths is

reduced, the patient must assume a greater amount

of the work of breathing. The potential disadvantage of this strategy is the increase in work of breathing due to the resistance inherent in the inspiratory

demand valves used in modern mechanical ventilators.71 This work may be sufficient to cause the

weaning attempt to fail in some patients (eg, those

patients with severe obstructive lung disease or

significant respiratory muscle atrophy).

Another relatively new strategy for weaning has

been the use of pressure support ventilation, either

in conjunction with or in place of SIMV. Pressure

support ventilation permits the mechanical flow of

fresh gas after the patient initiates a breath. Because

the patient retains control of the total respiratory

rate and the depth and duration of assisted breaths,

they are generally more comfortable while receiving mechanical ventilatory support. This mode

offsets the increased work of breathing inherent in

the ventilator circuit due to resistance to gas flow in

the circuit. Most authorities do not recommend

reducing the SIMV rate below four breaths per

minute unless pressure support ventilation is utilized concomitantly.

Several general comments should be made regarding medical plans for ventilatory weaning:

• Adequate rest periods are essential to prevent respiratory muscle fatigue.

• The physician must constantly assess the

patient’s progress during weaning.

• Arterial blood gas measurements are no

substitute for clinical judgment.

• Hypercarbia is a late finding of inadequate

respiratory muscle strength.

• The patient must be observed for tachypnea,

paradoxical respiratory movements, use of

accessory muscles of inspiration, and diaphoresis.

VENTILATORS AVAILABLE FOR COMBAT CASUALTY CARE

A large number of mechanical ventilators are in

the inventories of the medical departments of the

U.S. armed forces. The following section discusses

the Puritan-Bennett PR-2 (manufactured by the

Bennett Medical Equipment, Los Angeles, Calif.),

which is pressure cycled; the Bear 33 (manufactured by Bear Medical Systems, Riverside, Calif.)

and the Lifecare PLV-100 and PLV-102 (manufactured by Lifecare Corporation, Lafayette, Colo.),

which are volume cycled; the Bennett MA-1 (manufactured by Bennett Medical Equipment, Los Angeles, Calif.), which is also volume cycled; and the

Impact Uni-Vent Model 750 M (manufactured by

Impact Instrumentation, West Caldwell, N.J.), which

is time cycled.

These ventilators are available for use with deployed medical units.

Puritan-Bennett PR-2

The Puritan-Bennett PR-2 is basically a converted

intermittent, positive-pressure breathing machine

and requires a source of compressed gas to function. The PR-2 is unique among the ventilators

under discussion here because it is pressure cycled.

The patient’s tidal volume cannot be directly set,

but is a result of the pressure limit and the inspiratory time. The limitations of the PR-2 in providing

mechanical ventilatory support to combat casualties are as follows:

• If the patient’s compliance decreases or airway resistance increases (a change in the

patient’s position, secretions in the airway,

bronchospasm, or patient agitation), the

same settings of airway pressure will result

in a decreased tidal volume and hypoventilation. Thus, we strongly advise that (a)

exhaled tidal volume be monitored and (b)

an alarm be attached.

• The patient may continue to spontaneously

breathe; however, competition may occur

as there is no mechanism to provide synchronization with the patient’s efforts. This

may result in high airway pressures and

barotrauma.
Acute Respiratory Failure and Ventilatory Management

703

• There is inaccurate control of FIO2 from

breath to breath when oxygen enrichment

is used. The higher the patient’s minute

ventilation, the lower the FIO2.

• When the respiratory rate increases and the

pressure is kept constant, inspiration may

end prematurely because the constant flow

rate results in higher peak airway pressures closing the inspiratory valve.

• To provide PEEP, an external valve must be

attached to the exhalation limb.

• These ventilators have limited peak flow

capabilities and may not be able to provide

for the traumatized casualty whose minute

ventilation demands are excessive.

Bear 33 and Lifecare PLV-100 and PLV-102

The Bear 33 and the Lifecare PLV-100 and PLV102 ventilators are all portable, electrically powered, microprocessor controlled, and volume cycled.

They do not require a separate source of compressed

gas unless oxygen enrichment is used. All these

ventilators can function in AC and SIMV modes,

with some limitations. All have an internal battery

and may be connected to an external battery as well.

The limitations of these ventilators are as follows:

• “Apnea, breathing-circuit disconnections,

leaks, exhalation-valve failures and occlusions may remain undetected....”72(p107)

Thus, it is recommended that an exhaled

volume monitor be used with these ventilators. There is no built-in capability for

monitoring exhaled volume.

• The provision for enriched oxygen supply is

passive and, except in the PLV-102, requires

an externally attached H-valve mechanism.

Three problems may be encountered:

1. the potential misassembly of the Hvalve, which may lead to obstruction

during patient inspiration;

2. the inaccuracy of the inspired oxygen

concentration, which mandates the use

of an oxygen analyzer (the FIO2 will be

± 10% if the patient has a stable minute

ventilation pattern, and greater if the

patient is unstable);

3. the automatic increase in tidal volume,

which occurs with increased oxygen

flow (in the Bear 33 and PLV-100), may

cause increased airway pressure and

barotrauma.

• “Substantial increases in work of breathing

varied with each ventilator so that the work

of breathing approached that of a patient

with high airway resistance: Bear 33, 41%;

Lifecare PLV-100 and PLV-102, 88%....”72(p107)

While supported on these ventilators, the

patient may appear dyspneic, and weaning

by IMV is likely to be unsuccessful unless

an external H-valve attachment is assembled.

• If a microprocessor failure occurs, the Bear

33 will not return to the previously set

parameters, but will revert to “apnea settings” of a tidal volume of 500 mL and a

respiratory rate of 16 breaths per minute.

• Lead–acid batteries are used in all these

ventilators. The life of this type of battery

will be shortened if it is allowed to remain

discharged. If fully functioning and

charged, the internal battery life is expected

to be 1 to 3 hours.

• To provide PEEP therapy, an external

valve needs to be attached on the exhalation limb.

Bennett MA-1

The Bennett MA-1 has been used for many years

in ICUs. This ventilator is electronically powered

and volume cycled (termination of inspiration). Its

limitations are as follows:

• There is no built-in monitoring of exhaled

volume.

• An externally attached H-valve apparatus

must be used to allow IMV to be used.

Hence, IMV is not synchronized and mechanical breaths may “stack” on top of spontaneous breaths.

• To provide PEEP, an external valve must be

attached to the exhalation limb.

Impact Uni-Vent Model 750 M

The Impact Uni-Vent Model 750 is the newest

ventilator to be accepted for military use. The

Impact is a portable, electrically controlled, timecycled, pressure-limited mechanical ventilator. It is

microprocessor-controlled and is capable of control, AC, or SIMV ventilatory modes. It has an

internal battery with a fully charged time capability

of 9 hours. This mechanical ventilator does require

a source of compressed gas to provide patient flow,
Anesthesia and Perioperative Care of the Combat Casualty

704

except during spontaneous breaths in the SIMV

mode. The limitations are as follows:

• There is no built-in capability for exhaled

volume monitoring.

• To institute PEEP therapy, an external PEEP

valve needs to be attached and several control settings must be adjusted to allow monitoring of the amount of PEEP within the

patient’s circuit.

• The work of breathing is not well studied

for this ventilator. An optional demand

valve (connected to a source of compressed

gas) is available, which provides an inspiratory flow of 60 L/min and is reported

to provide a small pressure assist (support)

of 2 to 3 cm H2O.

• If the optional demand valve is not used,

room air will be entrained through the

antiasphyxiation port during the patient’s

spontaneous breaths. This will decrease

the fractional concentration of oxygen provided to the patient.

• There is no measurement of the size of

spontaneous breaths taken during SIMV.

• The digital display of peak inspiratory pressure is hard to quantitate in the most common range of pressures (10–50 cm H2O).

Many of the mechanical ventilators projected for

use in the combat casualty setting are different from

those used in most peacetime hospitals. For this

reason, it would be prudent for medical personnel

who may be called on to care for patients with these

ventilators to familiarize themselves with their operating capabilities.

SUMMARY

Respiratory failure of a magnitude that requires

mechanical ventilation can be expected to occur in

10% to 15% of hospitalized casualties. The most

likely causes are ARDS, severe brain injury, and

severe torso injury during the postoperative phase.

The diagnosis of respiratory failure depends on the

observation of hypoxemia (PaO2 < 50 mm Hg while

breathing room air) and ventilatory failure (PaCO2 >

50 mm Hg). Although these findings indicate the

presence of severe pathophysiology, respiratory support with supplemental oxygen, incentive spirometry, and intratracheal suctioning may decrease the

need for intubation and mechanical ventilation.

Mechanical ventilation has several beneficial effects, including eliminating the work of breathing

for the casualty, maximizing the concentration of

inspired oxygen, and ventilating collapsed and

poorly ventilated alveoli. The latter changes cause

a decrease in the amount of intrapulmonary shunting and an increase in the functional residual capacity of the lung. However, high airway pressure

during expiration—especially in the presence of

hypovolemia—may lead to decreased venous return to the heart, a fall in cardiac output, and a

decrease in oxygen delivery. Barotrauma leading to

tension pneumothorax is a potentially fatal complication of mechanical ventilation but is unlikely to

occur if peak airway pressure is maintained below

50 cm H2O.

Military anesthesiologists and intensivists must

understand the design of deployable mechanical

ventilators, be able to choose the proper mode of

ventilation, and be able to select the appropriate

initial ventilatory settings. These required settings

include tidal volume, rate, peak gas flow, inspiratory-to-expiratory ratio, and the fractional concentration of oxygen. In addition, anesthesiologists

and intensivists must be familiar with the logistics

of oxygen supply.

Mechanical ventilators use three types of cycling: pressure, volume, and time. Both volumeand time-cycled ventilators allow for a constant

level of tidal volume, which makes them more effective than pressure-cycled ventilators whenever

pulmonary compliance or airway resistance is elevated. The initial settings that are selected for

mechanical support depend on the indication for

which the patient requires ventilatory support. Plausible initial settings are tidal volume, 10 to 15 mL/

kg; respiratory rate, 7 to 10 breaths per minute; and

inspired oxygen concentration, 40%. Both the respiratory rate and the oxygen concentration may

have to be increased, and flow rates and end expiratory pressures adjusted, if pulmonary injury is

present. A variety of parameters may be measured

to judge the effectiveness of ventilation and oxygenation (eg, systemic DO2 and the magnitude of

the arterial-venous shunt), but useful information

is also obtained from the subjective appearance of

the casualty. In addition, in deployable hospitals,

from the practical standpoint, an assessment as to

the effectiveness of ventilation will depend on measurement of PaO2 and PaCO2 measured with a blood

gas analyzer, SaO2 measured with a pulse oximeter,

a chest radiogram, and the airway flow and pressure measurements from the controls and sensors of
Acute Respiratory Failure and Ventilatory Management

705

the mechanical ventilator. The goal is to maximize

oxygenation while minimizing airway pressures

and inspired oxygen concentration.

Discontinuation of mechanical ventilation should

be considered only if the underlying cause of the

respiratory failure has been reversed. Multiple

criteria have been advanced to guide the weaning

process once the decision has been made to discontinue mechanical support. Among them are (a) PaO2

greater than 60 mm Hg when FIO2 is less than 0.5, (b)

the ability to produce a spontaneous vital capacity

greater than 10 mL/kg, and (c) the ability to generate a negative inspiratory effort greater than 30 cm

H2O. None of these criteria are absolute. Premature discontinuation of mechanical ventilation and

extubation to make possible rapid evacuation—

especially when it is by air—is to be avoided in

combat casualties.

REFERENCES

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database describing combat wounds and the circumstances of wounding is the Wound Data and Munitions

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These data are stored at the National Naval Medical Center, Bethesda, Maryland. Access is controlled by the

Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799; telephone (301) 295-

6262. Three summary volumes contain extensive abstracts of the statistical data and can be obtained from

Defense Documentation Center, Cameron Station, Alexandria, Virginia 22304-6145; telephone (703) 545-6700

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2. Arnold K, Cutting RT. Causes of death in United States military personnel hospitalized in Vietnam. Milit Med.

1978;143:161–164.

3. Wright S. US Army Medical Department Center and School, Fort Sam Houston, Tex. Personal communication,

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4. Whatmore D. Lieutenant Colonel, Medical Corps, US Army. Personal communication, August 1994.

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8. Huller T, Bazini Y. Blast injuries of the chest and abdomen. Arch Surg. 1970;100:24–30.

9. Blood CG. Analyses of battle casualties by weapon type aboard US Navy warships. Milit Med. 1992;157(3):124–130.

10. Fein A, Leff A, Hopewell P. Pathophysiology and management of the complications resulting from fire and the

inhaled products of combustion. Crit Care Med. 1980;8(2):94–98.

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12. Levine B, Petroff P, Slade C, Pruitt B. Prospective trials of dexamethasone and aerosolized gentamicin in the

treatment of inhalation injury in the burned patient. J Trauma. 1978;18(2):188–193.

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to mustard gas inhalation. Chest. 1991;100:1436–1441.

14. Bellamy RF, ed. Combat Casualty Care Guidelines: Operation Desert Storm. Washington, DC: US Department of the

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15. Dolev E. Wartime trauma: Lessons and perspectives. Internat Anes Clin. 1987;25(1):191–202.

16. Teabeaut J. Aspiration of gastric contents: An experimental study. Am J Pathol. 1951;28:51.

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18. Fanning G. The efficacy of cricoid pressure in preventing regurgitation of gastric contents. Anesthesia.

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1971;122:260–268.

26. Hammerschmidt D, Weaver L. Association of complement activation in elevated plasma C5A with ARDS:

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27. Sutter PM, Schlobohm RM. Determination of functional residual capacity during mechanical ventilation.

Anesthesiology. 1974;41:605–607.

28. Bernard GR, Luce JM, Sprung CL. High dose corticosteriods in patients with the Adult Respiratory Distress

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32. Abrams JH, Gilmour IJ, Kriett JM, et al. Low frequency positive pressure ventilation with extracorporeal carbon

dioxide removal. Crit Care Med. 1990;18(2):218–220.

33. Van de Water J, Watring W, Linton L. Prevention of postoperative pulmonary complications. Surg Gynecol

Obstet. 1978;135:129.

34. Latimer RG, Dickman M, Day WC, Gunn ML, Schmidt CD. Ventilatory patterns and pulmonary complications

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36. Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians:

Instructor Manual. 5th ed. Chicago, Ill: American College of Surgeons; 1993.

37. Berlauk JF. Prolonged endotracheal intubation vs tracheostomy. Crit Care Med. 1986;14(8):742–745.

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39. Marini J, Wheeler A. Mechanical ventilation. In: Critical Care Medicine—The Essentials. Baltimore, Md: Williams

& Wilkins; 1989: 65.

40. Biondi JW, Shulman DS, Soufer R, et al. The effect of incremental positive end-expiratory pressure on right

ventricular hemodynamics and ejection fraction. Anesth Analg. 1988;67(2):144–151.

41. Shelhamer JH, Natanson C, Parrillo JE. Positive end-expiratory pressure and adults. JAMA. 1984;251(20):

2692–2695.

42. Petersen GW, Baier H. Incidence of pulmonary barotrauma in a medical ICU. Crit Care Med. 1983;11(2):67–69.

43. Haake R, Schlictig R, Ulstad D, Henschen R. Barotrauma, pathophysiology, risk factors and prevention. Chest.

1987;91(4):608–613.

44. Knaus WA, Wagner DP. Multiple systems organ failure: Epidemiology and prognosis. Crit Care Clin. 1989;5(2):

221–232.

45. Barach A, Martin J, Eckman M. Positive pressure respiration and its application to treatment of acute pulmonary

edema. Ann Int Med. 1938;12:754.

46. Gallagher TJ, Civetta JM, Kirby RR. Terminology update: Optimal PEEP. Crit Care Med. 1978;6(5):323–326.

47. Petty TL. The use, abuse, and mystique of positive end-expiratory pressure. Am Rev Respir Dis. 1988;138(2):

475–478.

48. Lodato R. Oxygen toxicity. Crit Care Clin. 1990;6(3):749–765.

49. Tobin M, Lodato R. Respiratory monitoring in the ICU. Pulmonary and Critical Care Update. 1988;3(22):1.

50. Roussos C, Macklem P. The respiratory muscles. N Engl J Med. 1982;307(13):786–797.

51. MacIntyre NR. Respiratory function during pressure support ventilator. Chest. 1986;89(5):677–683.

52. Hubmayr RD, Gay PC, Tayyab MM. Respiratory system mechanics in ventilated patients: Techniques and

indications. Mayo Clin Proc. 1987;62(5):358–368.

53. Coppolo DP, May JJ. Self-extubations: A 12-month experience. Chest. 1990;99(5):1319–1320.

54. Garnett AR, Ornato JP, Gonzales ER, Johnson EB. End-tidal carbon dioxide monitoring during cardiopulmonary

resuscitation. JAMA. 1987;257(4):512–515.

55. Sanders AB, Kern KB, Otto CW, Milander MM, Eury GA. End-tidal carbon dioxide monitoring during

cardiopulmonary resuscitation: A prognostic indication for survival. JAMA. 1989;2629100:1347–1351.

56. Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors

as therapeutic goals in high-risk surgical patients. Chest. 1988;94(6):1176–1186.

57. Wolf Y, Cotev S, Perel A, Manny J. Dependence of oxygen consumption on cardiac output in sepsis. Crit Care

Med. 1987;15(3):198–203.
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58. Cain SM. Supply dependence of oxygen uptake in ARDS: Myth or reality? Am J Med Sci. 1984;288(3):119–124.

59. Gutierrez G, Pohil RJ. Oxygen consumption is linearly related to O2 supply in critically ill patients. J Crit Care.

1986;1(1):45.

60. Mohsenifar Z, Goldback P, Tashkin D, Campisi D. Relationship between O2 delivery and O2 consumption in the

Adult Respiratory Distress Syndrome. Chest. 1983;84(3):267–271.

61. Yu M, Takanishi D, Myers SA, et al. Frequency of mortality and myocardial infarction during maximizing

oxygen delivery: A prospective, randomized trial. Crit Care Med. 1995;23(6):1025–1032.

62. Knox JB. Oxygen consumption–oxygen delivery dependency in adult respiratory distress syndrome. New

Horizons. 1993;1(3):381–387.

63. Demling RH. Adult respiratory distress syndrome: Current concepts. New Horizons. 1993;1(3):388–401.

64. Brunel W, Coleman D, Schwartz D, Peper E, Cohen N. Assessment of routine chest roentgenograms and the

physical examination to confirm endotracheal tube position. Chest. 1989;96(5):1043–1045.

65. Strain DJ, Kinasluity GT, Vereen LE, George RB. Value of routine daily chest X-rays in the medical intensive care

unit. Crit Care Med. 1985;13(7):534–536.

66. Sporn PH, Morganroth ML. Discontinuation of mechanical ventilation. Clin Chest Med. 1988;9(1):113–126.

67. Morganroth M, Grum C. Weaning from mechanical ventilation. J Intern Care Med. 1988;3(2):109.

68. Sahn SA, Lakshninarayan S. Bedside criteria for the discontinuation of mechanical ventilation. Chest.

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69. Morganroth ML, Morganroth JL, Nett LM, Perry TL. Criteria for weaning for prolonged mechanical ventilation.

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70. Cohen C, Zagelbaum G, Gross D, Roussos C, Macklem P. Clinical manifestations of inspiratory muscle fatigue.

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71. Hughes C, Poparich J. Overcoming common problems with mechanical ventilation valve systems. J Crit Illness.

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Acute Renal Failure

709

Chapter 26

ACUTE RENAL FAILURE

JACK MOORE, JR., M.D.*

INTRODUCTION

MILITARY HISTORY

World War II

Korean War

Vietnam War

Military and Civilian Experience Since Vietnam

PATHOGENESIS OF ACUTE RENAL FAILURE

Classic Mechanisms of Renal Failure

The Nature of Cellular Injury

CLINICAL ASPECTS OF ACUTE RENAL FAILURE

Distinguishing Between Acute Oliguria and Acute Renal Failure

Diagnostic Assessment

PREVENTION OF ACUTE RENAL FAILURE

Identification of High-Risk Patients

Volume Expansion

Pharmacological Interventions

PROTECTION FOR PATIENTS IN INCIPIENT RENAL FAILURE

Pharmacological Therapy of Acute Oliguria

Prevention of Acute Renal Failure in High-Risk Patients

CONSERVATIVE TREATMENT OF ACUTE RENAL FAILURE

Nutritional Support

Fluid and Diuretic Therapy

Management of Acid–Base Disturbances

Management of Electrolyte Imbalances

APPROACHES TO DIALYSIS

Conventional Hemodialysis

Peritoneal Dialysis

Hemofiltration

DIALYTIC MANAGEMENT OF ACUTE RENAL FAILURE

Indications for Dialysis

Complications of Dialysis

Practical Aspects of Dialysis

Timing and Frequency of Dialysis

PROGNOSIS AND OUTCOME OF ACUTE RENAL FAILURE

SUMMARY

*Colonel, Medical Corps, U.S. Army, (ret); formerly, Chief, Nephrology Service, Walter Reed Army Medical Center, Washington, D. C.;

Nephrology Consultant to The Surgeon General; and Associate Professor of Medicine, Uniformed Services University of the Health Sciences,

4301 Jones Bridge Road, Bethesda, Maryland 20814-4799; currently, Associate Professor of Medicine, Division of Renal Diseases and

Hypertension, Department of Medicine, The George Washington University Medical Center and School of Medicine, Washington, D. C. 20037
Anesthesia and Perioperative Care of the Combat Casualty

710

INTRODUCTION

Acute renal failure (ARF) is a disorder manifested by a sudden decline in renal function and is

characteristically accompanied by (a) changes in

the concentrations of electrolytes and nitrogenous

waste products in the blood and (b) a reduction in

urinary output. While ARF has diverse etiologies,

most patients sustain injury from renal ischemia,

nephrotoxins, or both. ARF usually occurs in the

setting of serious injury or illness, and as such,

substantially affects morbidity and mortality.

The morbidity and mortality of ARF depend on

several factors including the etiology and clinical

features of the disease as well as the patient’s underlying condition. The mortality of ischemic,

oliguric ARF, usually occurring in patients who

have sustained trauma or patients with medical or

surgical illnesses with shock, exceeds 50%, and may

be higher depending on the patient population under study. Conversely, ARF accompanied by substantial urinary output (ie, nonoliguric ARF, in

which nephrotoxins play an important role in the

pathogenesis1

) is usually associated with a lower

mortality.2 Finally, covariables such as age and

associated extrarenal organ involvement adversely

affect outcome.

These patients do not die of renal failure per se,

but the presence of renal failure substantially

increases the mortality. The availability of dialysis

to control fluid and electrolyte imbalances and

nitrogenous waste retention has prolonged the

duration of illness, with patients surviving 4 to 6

weeks instead of several days. Nonetheless, many

eventually succumb to overwhelming infections

(approximately 70%) or pulmonary complications

(approximately 30%). The impact of multiple organ

failure on survival with ARF is such that when

ARF develops without concomitant extrarenal organ failure, as is often seen in obstetrical and

radiocontrast injury, the mortality is usually lower

than 10%.3

Although we have the capability to provide dialysis to the combat casualty, it has become axiomatic that dialysis and modern critical care medicine

have not exerted an important effect on the mortality associated with ARF. The reasons for this are not

clear; they may relate to an increase in the mean age

of the population that sustains ARF or to increased

comorbidity in this population. Nonetheless, our

current efforts are directed toward preventing ARF,

providing better nutrition, and developing more

effective drugs to treat infection. Because there is

little reason to believe that improvements in dialysis will affect outcome in the majority of patients,

we have sought to expand our understanding of the

pathophysiology of ARF, with the ultimate goal of

preventing renal injury.

It is not the purpose of this chapter to exhaustively review the literature on either experimental

or clinical ARF. Such purpose, given the thousands

of papers that have been written on this subject,

would be unrewarding. The principles outlined

herein are designed to assist medical officers, including nephrologists, in the prevention, diagnosis,

and management of ARF in combat casualties.

World War II

ARF has been recognized as a serious problem

for military physicians since 1941, when E. G.

Bywaters and D. Beall4 published their classic

description of rhabdomyolysis and myoglobininduced ARF in four patients who sustained

crush injuries in the bombings of London, England,

during World War II. Since then, our understanding of the pathophysiology of ARF has increased, and our treatment options have expanded

substantially. However, posttraumatic ARF continues to be associated with a persistently high

mortality,5 and is a complex medical problem for

those who plan the delivery of military healthcare

during wartime.

The salient features of the incidence, treatment,

and outcomes of combat casualty–associated ARF

in U.S. military forces in modern armed conflicts

have been reviewed in detail6 and are summarized

here to emphasize the lessons learned.

During the World War II era, blood chemistry

analyzers were primitive and not widely available;

thus, ARF was usually recognized by the presence

of oliguria, hypertension, and pulmonary edema,

and only occasionally by azotemia—making it likely

that only severe ARF was recognized. Nonoliguric

ARF was undoubtedly under-diagnosed. Using

data that had been collected and analyzed during

1944 and 1945, but not published until 1952, the

Board for the Study of the Severely Wounded7 included records of patients who were oliguric durMILITARY HISTORY
Acute Renal Failure

711

ing shock and died within 24 hours of injury. Inclusion of these patients probably led to over-emphasis of the role of parenchymal ARF in their mortality. The cited mortality of ARF—90%—is therefore

problematic, although that figure became accepted

as the standard mortality of ARF in its untreated

state. A more accurate interpretation of the data

would place the mortality between 70% and 80%.

ARF’s severity may well have been increased by the

medical realities of the war: evacuation times exceeded several hours, and shock was treated with

plasma because supplies of blood and crystalloid

fluids like saline were limited. Accordingly, some

of the lessons learned from the study of ARF during

the World War II era may not be applicable currently: more effective therapy of shock in subsequent conflicts radically changed the apparent incidence and clinical characteristics of ARF.

Korean War

Nonetheless, recognition of the impact of ARF in

World War II led to anticipation of the problem of

posttraumatic ARF in troops engaged in the Korean

War. At that time, early forms of hemodialysis had

been developed and were utilized at a center for

kidney treatment established at Wonju, Korea,

in 1951. The incidence of ARF during the Korean

War was approximately 1 per 200 seriously

wounded. The decrease in the mean duration of

shock and more-rapid evacuation of wounded, in

conjunction with successful use of hemodialysis in

the combat zone, resulted in substantial reductions

in the observed mortality due to ARF: down to 53%

to 60%. In this conflict, ARF was the subject of

careful clinical observation, which indicated that

the mortality was often due to shock and multiple

organ failure.8,9 Concomitantly, although the overall mortality of patients with ARF remained quite

high, two tenets of the treatment of established ARF

were developed:

1. Attempts were made to provide nutritional

support utilizing high-caloric, low-volume

fluid regimens developed for use in oliguric

patients.

2. Hemodialysis was utilized in an effort to

attenuate the effects of uremia.

Vietnam War

Many of the lessons learned in Korea were used

to advantage during the Vietnam War. The 629th

Medical Renal Detachment was formed at Brooke

General Hospital in 1965 and was attached to the

Third Field Hospital in Saigon in 1966. Other renal

units were placed at Clark Air Force Base in the

Philippines and on two U.S. Navy hospital ships.

These renal intensive care units had the capability

of delivering complete care to casualties with ARF.

Nephrologists prescribed and supervised dialysis,

which was performed by nurses and corpsmen

trained in dialysis. These personnel comprised “K”

teams, which gained a substantial body of experience in the management of ARF and the numerous

medical problems with which it was associated.

During the Vietnam War, two factors contributed to the decrease in the incidence of ARF to

approximately 1 per 600 seriously wounded:

1. Rapid volume resuscitation of casualties,

instituted near the geographical site of injury, was widely practiced in Vietnam and

reduced the duration of shock.

2. The use of helicopters substantially reduced evacuation times.

Nonetheless, the 55% to 65% mortality of ARF was

nearly identical to that seen in the Korean War,

despite the facts that hemodialysis was utilized

extensively for more severe forms of ARF and peritoneal dialysis was utilized in milder forms of ARF

(eg, hemoglobinuria associated with malaria).

During the Vietnam War, medical officers reported several landmark studies of casualties with

ARF. In 1974, W. J. Stone and J. H. Knepshield10

described their experience with 62 casualties with

ARF who received care in the renal unit of the 629th

Medical Detachment in Saigon, and noted a 69%

mortality despite the liberal use of dialysis. Sepsis,

respiratory failure, bleeding, and hyperkalemia were

the causes of death; the two former causes accounted

for 89% of the total mortality. In 1972, R. E. Lordon

and J. R. Burton11 described their experience with 67

casualties with ARF treated at Clark Air Force Base.

Although frequent dialysis was utilized, the mortality was 63%. These investigators also emphasized the role of infection in ARF, which accounted

for 72% of the deaths. In 1975, J. D. Conger12 conducted a prospective trial of “prophylactic” dialysis compared with dialysis for more conventional

indications in 18 patients treated for ARF aboard

the USS Sanctuary. This study purported to examine the role of prophylactic dialysis; however, it is

more accurately characterized as a study of intensive dialysis. Although differences in mortality

between patients who received intensive prophylactic dialysis compared with those dialyzed for
Anesthesia and Perioperative Care of the Combat Casualty

712

20

10

0

30

40

50

60

70

80

90

% Mortality

Type of Treatment

conventional indications failed to reach statistical

significance, the former group suffered fewer complications. The collective experience with the management of ARF in the Vietnam War served to

validate the role of hemodialysis in the management of posttraumatic ARF. Because hemodialysis

was simultaneously being widely applied in the

civilian treatment of ARF, due in part to the pioneering efforts of R. C. Swann and J. P. Merrill13 in

Boston in 1953, it became an accepted treatment

modality for most patients with ARF. Selected

features of the experience with ARF in conflict are

presented in Figures 26-1 and 26-2.

A new expression of ARF, in which renal dysfunction developed over several days, became evident in both the Vietnam War and the civilian sector

during the period 1965 through 1974.14,15 ARF was

noted to develop in critically ill patients with multiple organ failure and was attributed to multiple

etiologies, including sepsis and exposure to

nephrotoxic drugs. Although some patients required only conservative management, others required dialytic support. At present, the concept of

ARF developing without overt shock has reached

its fullest expression in the patient with multiple

organ failure.16 Patients with ARF in association

with multiple organ failure now represent a large

fraction of patients with ARF seen in peacetime, and

providing support to them represents a major

mechanism for regular and reserve medical officers’ maintaining their “go-to-war” skills.

% Mortality

100

90

70

80

60

50

40

30

20

10

0

Saigon

(80)

Clark

(67)

Japan

(29)

Navy Ships

(18)

Fig. 26-2. Mortality of casualties from acute renal failure in

the Vietnam War, stratified as to the location of their dialysis treatment. The numbers in parentheses represent the

number of patients treated in each location. Adapted with

permission from Butkus DE. Post-traumatic acute renal

failure in combat casualties: A historical review. Milit Med.

1984;149:121. Military Medicine, Official Journal of the Association of Military Surgeons of the United States (AMSUS).

Overall

KC-Rx

Conservative

Rx

Pre-HD HD-treated

Military and Civilian Experience Since Vietnam

The experience gained from the wartime treatment of ARF, augmented by knowledge gained

from the care and study of patients with ARF since

the mid-1970s, has engendered several principles

that guide our planning for the care of combat

casualties:

1. ARF is a substantial problem in casualties

with serious injuries and is often heralded

by oliguria due to shock.

2. Identification of patients at high risk for

ARF is possible, although there is surprisingly little objective evidence that such

identification has been clinically effective.

3. ARF may develop at any time during the

treatment and management of the seriously wounded, and even after initial stabilization may result from injury induced

by anesthesia, hemolysis, sepsis, or drug

toxicity.

4. Given the widespread application of dialysis, casualties rarely die of ARF but

instead die of the infections and sequelae

of multiple organ failure that accompany

severe injuries.

Fig. 26-1. Mortality of casualties from acute renal failure

during the Vietnam War. Pre-HD refers to patients who

were treated before hemodialysis was available. KC

refers to patients who were treated in the specialized

Kidney Center in the 3rd Field Hospital in Saigon. Data

source: Butkus DE. Post-traumatic acute renal failure in

combat casualties: A historical review. Milit Med.

1984;149:117–124.
Acute Renal Failure

713

A comprehensive review of the mortality of different forms of ARF, factored for the era in which it

occurred, has been provided by W. F. Finn,17 part of

whose data are summarized in Figure 26-3.

Deployable Medical Systems

To provide healthcare for casualties of future

conflicts, the Department of Defense has revised

doctrine to include the concept of Deployable Medical Systems (DEPMEDS).18 Military and civilian

medical experts, many with experience in conflict,

drew up a list of disorders likely to be encountered

in combat. Projected incidence data and treatment

protocols were defined for each of these patient

conditions (this subject is discussed more fully in

Chapter 6, Deployable Hospitals). More than 20%

of identified patient conditions would be expected

to be accompanied by the development of ARF in at

least a cohort who sustain the illness or injury. In

general, it is estimated that 5% of casualties who

sustain either moderately severe, multiple, fragment injuries to the thorax or abdomen; isolated

extremity injuries with muscle damage; or severe

malaria will potentially require dialytic support at

the fourth echelon. Ten percent of casualties who

sustain either severe injuries to the thorax or abdominal cavities, alone or in combination, or major

crush injuries, particularly of the lower extremities,

are expected to require dialysis. Obviously, such

figures could vary depending on the location of the

conflict, its intensity, the types of weapons systems

utilized, and the triage and evacuation policies of

the theater commander. For example, given equal

rates and severity of injury, there would likely be

more ARF in a conflict in an arid environment, in

which water supplies are limited and personnel are

dehydrated, than in a more temperate climate.

Under the DEPMEDS doctrine, all equipment

and consumable supplies required to perform

hemodialysis are in a self-contained module. Only

electrical generators are not included in the module. The cohort of personnel required to provide

dialysis are delineated, and include a nephrologist,

a dialysis-trained nurse, and corpsmen trained in

dialysis. This team is similar to the “K” teams of

Korea and Vietnam.

Civilian Disasters

Although much of the contingency planning for

the delivery of care to patients with ARF in future

conflicts is based on experience gained in prior

conflicts, these concepts have been validated recently in a peacetime situation analogous to combat. The earthquake in 1988 in Armenia produced

more than 600 patients with ARF secondary to crush

injury. An international team of medical personnel, in conjunction with support from the dialysis

industry, was rapidly mobilized to provide personnel and supplies for over 400 patients, at times

administering 150 dialysis treatments per day. The

magnitude of the disaster required that more than

80,000 lb of dialysis supplies be shipped from the

United States. Intrinsic resources in Armenia and

in Moscow were utilized for at least one third of the

patients.19 Because much more ARF could have

been encountered if more casualties had survived,

the magnitude of the problem of ARF in this setting

underscores the need for the capability to rapidly

mobilize large quantities of consumable supplies,

sophisticated medical equipment, and appropriately trained personnel. It is this expeditious

deployability of healthcare—eliminating the need

to preposition personnel, supplies, and equipment—

that is the basic tenet of DEPMEDS.

PATHOGENESIS OF ACUTE RENAL FAILURE

Classic Mechanisms of Renal Failure

The pathogenesis of ARF has been the subject of

considerable experimental study, clinical observation, and review.20–30 Information obtained from

nearly all experimental models of ARF indicates

that both renal blood flow and the glomerular filtration rate decline early after the initial insult. This

early period, lasting from hours to days, is termed

the initiation phase. Gradually, renal blood flow

1,500

Posttraumatic

(mortality 53%)

Surgical

(mortality 51%)

0

500

1,000

Number of Patients

Fig. 26-3. Mortality of acute renal failure between 1970

and 1979 in surgical and trauma patients. Data source:

Finn WF. Recovery from acute renal failure. In: Brenner

BM, Lazarus M. Acute Renal Failure. Philadelphia, Pa: WB

Saunders; 1983: 755.

Dead

Survivors
Anesthesia and Perioperative Care of the Combat Casualty

714

returns toward normal, while the glomerular filtration rate remains depressed. This period, which

may last from days to weeks, is called the maintenance phase. In general, when ARF persists for

longer than 3 months, end-stage renal disease is

assumed.

Four mechanisms have been proposed to explain

the pathophysiology of ARF (Exhibit 26-1). These

mechanisms—renal vasoconstriction, reduction in

glomerular filtration, tubular obstruction, and back

leak of filtrate—have been identified and delineated using models in which the renal artery is

either clamped or infused with norepinephrine, or

in which hemorrhage of sufficient severity is produced to result in sustained systemic hypotension.

This latter model is of particular interest as it closely

mimics the clinical setting of posttraumatic ARF,

and because the kidney is exposed to the multiplicity of hormonal and neurogenic alterations that

accompany shock. A similar model involves the

injection of glycerol into a large muscle of an animal, which results in muscle necrosis and vascular

pooling in the involved extremity, and is closely

analogous to crush injury.

The classic mechanisms of ARF can be divided

into (a) those that exert primarily vascular effects

and (b) those that exert tubular effects. The vascular

mechanisms include reductions in both renal blood

flow and the intrinsic filtration capability of the

glomeruli. The tubular mechanisms include tubular obstruction by casts and back leak of filtrate.

Undoubtedly, all four mechanisms participate in

the injury seen in existent models of ARF. The

contribution of each, however, is likely to differ

depending on the model used. Thus, reduced renal

blood flow is the prominent feature of ARF induced

by hemorrhagic hypotension, while intratubular

obstruction by casts is more prominent in ARF

induced by glycerol. Models most useful for the

study of clinical ARF combine features of all suspected mechanisms.

Vascular Mechanisms

An early decrease in renal blood flow and an

increase in renal vascular resistance are consistent

findings in virtually all types of experimental ARF.

The reduction in renal blood flow results in integrated hormonal, neural, and intrinsic renal responses, all of which are designed to restore the

extracellular fluid, renal blood flow, and renal function. ARF is the result when these mechanisms fail.

Reduced Extracellular Fluid Volume. Sensor

mechanisms for detection of decreased extracellular fluid include baroreceptors located throughout

the body. These receptors are sensitive to mechanical stretch and transmural pressure. Intrathoracic

volume receptors exist in both the atria and the

pulmonary capillaries. Activation of these receptors results in increased traffic both in sympathetic

fibers and in cranial nerves IX and X, the latter to

centers in the hypothalamus and medulla. Arterial

volume sensors in the carotid sinus have been postulated to provide stimuli for the kidney to retain

sodium and water, although the mechanisms of

their actions have not been completely defined.

Finally, baroreceptors located in the juxtaglomerular

apparatus of the kidney are exquisitely sensitive to

reductions in renal perfusion pressure. Their activation initiates the release of renin and the subsequent formation of the vasoconstrictor angiotensin

II, and release of the sodium-retaining hormone

aldosterone. Effector mechanisms react to reduced

renal blood flow and induce vasoconstriction and

sodium and water retention, both of which are

designed to restore the extracellular fluid. These

mechanisms include catecholamines, angiotensin

II, arginine vasopressin, aldosterone, vasoconstrictor prostaglandins, and intrinsic renal tubular

events, which participate in an integrated response.

Decreased Glomerular Filtration. The second

vascular mechanism that occurs is decreased filtraEXHIBIT 26-1

CLASSIC MECHANISMS OF ACUTE

RENAL FAILURE

Vascular Mechanisms

Renal vasoconstriction

Reduced blood flow

Increased resistance

Reduced glomerular filtration

Endothelial morphology

Reduced glomerular area

Tubular Mechanisms

Luminal obstruction

Cellular debris

Casts

Back leak of filtrate

Inulin

Other markers
Acute Renal Failure

715

tion capability of the glomeruli. Filtration is a

function of the intrinsic permeability characteristics of the glomerular capillary membrane, the surface area available for filtration, and the net pressure for filtration (defined by Starling forces) across

the glomerular capillaries. The aggregate capability for filtration is expressed by the term Kf

, and is

reduced pari passu the reduction in renal blood

flow, as the latter is a major determinant of glomerular filtration rate. Such reduction may be due

either to a direct effect of ischemia on the basement

membrane of the capillary or to reduction in the

surface area of the capillary, perhaps mediated by

angiotensin II.

Tubular Mechanisms

Obstruction. Obstructing casts originate from

cellular debris, principally sloughed epithelial cell

fragments and brush border membranes, which

coalesces with Tamm-Horsfall mucoprotein of

uroepithelial origin. The resultant obstruction of

the tubular lumen raises intratubular pressure in

excess of glomerular filtration pressure, so that

glomerular filtration ceases.

Back Leak. The second tubular mechanism is

back leak of filtrate, in which a marker of glomerular filtration rate, usually inulin, can be shown to

traverse the damaged tubular epithelium from the

tubular lumen into the renal circulation. Such movement of solute could be due either to disruptions in

intercellular bridges or, most likely, to impairment in

the ability of epithelial cells to restrict the transcellular

movement of normally excluded solutes.

The Nature of Cellular Injury

If the four events detailed above were sufficient

explanations for the mechanisms of ARF seen after

ischemic or nephrotoxic injury, we could infer that

maneuvers successful in ameliorating one or more

factors might exert a beneficial effect on the incidence or severity of renal injury. Unfortunately, the

results of such strategies have been largely inconsistent and only variably successful. The lack of

success could result from an inability to distinguish

precisely between the initiation phase of ARF, when

damage could putatively be reversed, and the maintenance phase, when injury is established. Alternatively, the factors believed to be operative in the

classic explanation of the pathophysiology of ARF

may be epiphenomena.

Since the early 1980s, our understanding of the

pathogenesis of ARF has been amplified substantially by investigation into the cellular basis of

ischemic and toxic renal injury.31 Research utilizing

kidney, heart, and liver tissue has formed a base for

additional studies with renal tubular epithelia,

mesangial and endothelial cells, as well as subcellular constituents. These studies have provided information that has vastly improved our understanding of the mechanisms by which ischemic and

nephrotoxic injury occur. Our current research

seeks to formulate unifying hypotheses of renal

injury, with the understanding that whole-organ

injury is predicated on, and best understood in the

context of, injury to its constituent cells.

Ischemia initiates a cascade of events that result

in cell death. Changes in cellular metabolism, alterations in cation adenosine triphosphatases (ATPases),

activation of phospholipases, generation of toxic

free radicals, and changes in the intrinsic nature of

the renal epithelial membrane itself32 have been

studied in a variety of models of ARF. While the

nature of the cellular response to injury varies somewhat depending on the model, these responses are

sufficiently homogenous that inferences about possible therapeutic maneuvers can be made.

Two of the central events in the cell’s response to

ischemia are (a) the simultaneous reduction in the

availability of adenosine 5í-triphosphate (ATP) and

other high-energy phosphate compounds and (b)

an increase in the formation of adenine nucleotide

degradation products.33 Without an adequate supply of ATP to maintain normal function, the cell’s

ability to maintain its metabolic integrity is severely

compromised. Thus, diminished activity of the

sodium-potassium ATPase results in the accumulation of intracellular sodium and swelling of the cell.

Similarly, inhibition of the calcium ATPase results

in cytosolic and mitochondrial calcium overload,

with impairment of the functional integrity of the

electron transport chain.34,35 These findings have

led to the use of stimulators of sodium-potassium

ATPase such as thyroid hormone, which has been

found to be beneficial in a number of different

models of ARF.36 Similarly, some investigators37

have demonstrated a beneficial effect of calcium

channel blocking agents such as verapamil.

The results of ischemia are (a) the metabolism of

ATP to hypoxanthine and (b) loss of nucleosides

from the cell.30 This latter event inhibits the regeneration of ATP and cell recovery. During

reperfusion, the enzyme xanthine oxidase, which is

formed during periods of ischemia from xanthine

dehydrogenase, converts hypoxanthine to xanthine,

with the concomitant generation of toxic free radicals through iron-requiring reactions known as the
Anesthesia and Perioperative Care of the Combat Casualty

716

Prerenal Azotemia

Absolute blood loss

Absolute or relative loss of extracellular fluid

Heart failure

Liver failure

Nephrotic syndrome

Postrenal Azotemia

Intravesicular obstruction

Retroperitoneal hemorrhage

Ureteral injury with single kidney

Intrinsic Acute Renal Failure

Renal ischemia

Nephrotoxins

Acute glomerulonephritis

Acute tubulointerstitial nephritis

Haber-Weiss and Fenton reactions.38–40 Inhibition

of xanthine oxidase by allopurinol prevents the

irreversible degradation of hypoxanthine, so that

when ischemia resolves, purine salvage pathways

can utilize adenine nucleotides for resynthesis into

ATP.41

Activation of phospholipase A2 results in

peroxidation of lipids in the cell membrane, a phenomenon that can be measured by the accumulation of malondialdehyde. Phospholipase A2 is activated by excessive concentrations of calcium, which

may result from diminished activity of calcium

ATPase. Moreover, with reperfusion, enzymatic

changes occur that result in the formation of large

quantities of hydrogen peroxide and the hydroxyl

ion.39,40 These moieties are extremely toxic to cell

contents. In the laboratory, the use of free radical

scavengers such as superoxide dismutase and dimethyl thiourea has shown some promise in abrogating renal injuries caused by oxygen-derived free

radicals.42

Taken collectively, the voluminous literature that

has appeared since the early 1980s on the cellular

basis of ARF demonstrates how much our understanding of this condition has expanded. As we will

see later, however, the therapeutic maneuvers that

follow from this understanding have not yet reached

the stage of widespread clinical application.

CLINICAL ASPECTS OF ACUTE RENAL FAILURE

No single definition of ARF is accepted by all

clinicians, although many accept the diagnosis if

the serum creatinine concentration increases by 50%

above its baseline. The blood urea nitrogen (BUN)

concentration is affected by diet, hydration, and medications; therefore, it is not, by itself, a particularly

valid marker of renal function. Acute renal dysfunction commonly is detected by alterations in volume of

urine, particularly acute oliguria, which is defined as

urinary output less than 400 mL/d, or approximately

20 mL/h. Acute anuria is defined as urinary output

less than 50 to 100 mL/d, but this is an uncommon

manifestation of ARF. Polyuria in the context of

acute renal dysfunction should be reserved to describe urinary output of several liters of urine daily.

Individuals who excrete urine in these amounts are

often found to have partial urinary tract obstruction. The term nonoliguric characterizes the substantial portion of patients who have significant

ARF, yet maintain urinary output of 1 to 2 L/d.

Distinguishing Between Acute Oliguria and

Acute Renal Failure

Operationally, the differences between acute

oliguria and ARF are substantial (Exhibit 26-2). The

former term implies that there may be a reversible

aspect of the renal dysfunction (ie, prerenal or

postrenal injury), while the latter connotes injury

that may require days to weeks to resolve.

Prerenal azotemia is renal dysfunction that results

from any absolute or relative deficiency of blood or

extracellular fluid. The consequent reduction in

renal blood flow results in activation of the effector

mechanisms that already have been mentioned.

Urinary flow and sodium excretion decrease beEXHIBIT 26-2

cause the physiological response to perceived volume depletion is to conserve salt and water avidly.

Postrenal azotemia, which is generally caused by

obstruction of the urinary tract, elicits physiological responses that are similar to those seen in prerenal azotemia. The causes of obstructive injury

deserve emphasis, as they may not be seen frequently by nonsurgical physicians. First, obstruction of the ureters above the level of the bladder

DIFFERENTIAL DIAGNOSIS OF OLIGURIA
Acute Renal Failure

717

may result from pelvic trauma or surgery, in which

the ureters can be obstructed by blood or by inadvertent ligation. Rarely, obstruction may be the

first sign of a leaking aorta or vena cava. In this

situation, blood causes a desmoplastic response

resulting in encasement of the ureters. Obviously,

supravesicular obstruction will only induce substantial renal failure should both ureters be involved, or if the patient has only one kidney, a

condition that occurs in 1 in 900 to 1,000 individuals. Second, individuals who are susceptible to

renal calculi may experience episodes of nephrolithiasis if climatic conditions are unfavorable (eg,

dehydration in the desert). However, renal calculus disease will cause oliguria or ARF or both if the

stones are bilateral, or if the stones form in a patient

who has a single kidney. And third, because it is

virtually routine to place an indwelling bladder

catheter in seriously injured casualties, many cases

of oliguria due to postrenal causes should be detected and definitively treated early, before substantial reduction in renal function occurs. The

most common cause of urinary tract obstruction is

an indwelling bladder catheter that has become

occluded or dislodged; therefore, the integrity of

the drainage system should be verified at the first

sign of diminishing urinary output.

Intrinsic ARF has a variety of causes. Moreover,

any prerenal or postrenal condition can result in

established ARF if uncorrected for sufficient time.

The period that must elapse before reversible injury

becomes irreversible is variable. Thus, relatively

trivial insults result in renal injury in some patients,

while substantial insults can be tolerated by others

before renal dysfunction is irreversible. Such differences may result from the kidneys’ autoregulatory

ability. In the otherwise healthy human, the lower

limit of mean arterial pressure for autoregulation is

approximately 60 to 70 mm Hg. This corresponds

to systolic blood pressures of 80 to 90 mm Hg. The

time that renal blood flow can be maintained under

more severe hypotensive conditions is unknown.

Other factors besides those related to volume

depletion—including hypercapnia and hypoxemia,

frequent concomitants of acute respiratory failure—

can also result in decreased renal blood flow.43

Cross-clamping of the aorta results in the same

response even if a surgically induced alternate pathway for perfusion, around the aortic cross-clamp, is

provided to the kidneys.44 Agents that disrupt the

balance between systemic and intrarenal vasoconstrictor and vasodilatory hormones, which participate in the maintenance of renal blood flow, are

associated with marked reductions in renal blood

flow. These agents, including the nonsteroidal

antiinflammatory agents and angiotensin-converting enzyme inhibitors, are particularly injurious

when the extracellular fluid volume is subnormal,

and renal blood flow is predicated on the balance

between vasoconstrictor and vasodilator hormones.45 Finally, it is intuitive that renal injury

might be more likely or more severe with a combination of injurious factors than with a single factor.

Given the dependence of the kidneys on renal blood

flow for oxygen delivery, any situation in which

oxygen is reduced would make the kidneys more

susceptible to either ischemic or nephrotoxic insult.

Renal ischemia accounts for ARF in most patients, although nephrotoxic injury has become increasingly important in peacetime medical practice.1 Patients who sustain nephrotoxic injury often

have sepsis, and the coexistent hemodynamic

changes associated with sepsis often result in renal

ischemia and undoubtedly enhance the injurious

effects of nephrotoxic substances, drugs, or diagnostic agents.

The military physician’s task is to distinguish

between oliguria that results from correctable causes

(ie, prerenal or postrenal failure) and established

ARF. Although the spectrum of causes of ARF in a

peacetime environment is quite broad, relatively

few disorders cause ARF on the battlefield; and

many of the rarer causes of ARF in peacetime practice, such as acute glomerulonephritis, are not likely

to be encountered at all by medical officers dealing

with combat-associated ARF. Finally, the distinction between ischemic and nephrotoxic causes is

often artificial because a substantial portion of patients have elements of both types of injury.

Diagnostic Assessment

Collectively, the history, physical examination,

biochemical analyses of serum and urine, urinalysis, and judicious use of renal imaging studies almost always provide the information needed by the

clinician to determine whether there is a readily

reversible cause of acute renal dysfunction or the

patient has established ARF. Medical treatment

facilities in the combat zone will have limited laboratory capability, but rearward facilities, particularly fixed general hospitals, may have a wide range

of sophisticated diagnostic equipment. At times,

the volume status of the patient is difficult to assess,

and measurement of central venous pressure or

pulmonary capillary wedge pressure is necessary.
Anesthesia and Perioperative Care of the Combat Casualty

718

However, hemodynamic monitoring, while providing valuable information, can be time-consuming to

institute, and may delay fluid resuscitation and

prolong renal ischemia.

Patient History

The medical officer’s review of available records,

including flow sheets, nurses’ notes, and medications, is essential, particularly in patients who develop ARF during hospitalization. Recent hypotension, either profound or subtle but sufficient to

cause decreased renal perfusion, may have occurred,

and daily weights and accurately measured urinary

outputs may be of substantial value.

The patient’s history of drug therapy is also important, as many drugs, particularly antibiotics and

nonsteroidal antiinflammatory agents, can cause

nephrotoxic injury either alone or in concert with

decreased renal perfusion. Aminoglycoside antibiotics are associated with nephrotoxicity in approximately 10% of patients. Risk factors for toxicity include heart failure, liver disease, and other

states associated with decreased renal perfusion.46

The most powerful predictor of toxicity is the duration of therapy. Renal toxicity is seldom seen with

fewer than 5 to 7 days of therapy; the incidence

increases substantially if therapy exceeds 10 days.

Many patients with ARF have few symptoms

and signs other than those related to the causative

disorder. Symptoms are related to the rapidity of

onset and severity of dysfunction and the patient’s

underlying condition, and may include nausea,

vomiting, or altered mental status. A diffuse bleeding diathesis, with gastrointestinal, nasotracheal,

and puncture-site hemorrhage, may occur with severe azotemia. Typically, however, azotemia is

largely asymptomatic unless the BUN and creatinine exceed 100 to 120 mg/dL and 6 to 8 mg/dL,

respectively; or if azotemia develops extremely rapidly (eg, over 24–48 h). Acidemia can be asymptomatic; however, if severe, it may result in

hypotension from depression of myocardial performance or reduction in peripheral resistance.

Hyperkalemia may result in cardiac arrhythmias

and skeletal muscle weakness. The latter may be

extremely difficult to detect in the critically ill patient. All the features described above can be caused

by factors other than azotemia.

Some patients develop symptoms of volume overload rapidly, which may reflect aggressive fluid

therapy. Fluid therapy is frequently continued in

oliguric patients for several hours, until the significance of diminishing urinary output is finally appreciated. Although oliguria is the most common

manifestation, nonoliguric ARF is frequently seen

with nephrotoxic injury. As has been mentioned,

polyuria is characteristic of urinary tract obstruction, and anuria is typical of vascular catastrophes

or complete urinary tract obstruction.

Physical Examination

The physical examination is useful in helping to

determine whether the patient is volume depleted

or volume overloaded, or the urinary tract is obstructed. Crucial elements include assessments of

skin turgor and edema, and the cardiac, pulmonary,

and genitourinary examinations. Accurate weights

or fluid flow sheets or both, blood pressure assessment for orthostatic hypotension, and proof of a

properly draining urinary tract are essential.

Biochemical Analyses of Blood and Urine

The concentrations of BUN and creatinine increase steadily during the course of ARF because

production remains relatively constant while excretion is profoundly decreased. Daily increments of

BUN and creatinine usually average at least 20 to

30 mg/dL and 1.3 to 1.5 mg/dL, respectively. Morerapid incremental changes in the BUN may reflect

excessive catabolism or gastrointestinal hemorrhage, while excessive increments in the serum creatinine may reflect muscle necrosis from rhabdomyolysis. Although the measurement of renal

function using the serum creatinine concentration

is not as accurate as calculating clearances from

timed urine collections, it is sufficiently accurate for

diagnosing posttraumatic renal dysfunction and

for initiating rational therapy.

Other abnormalities commonly encountered

include metabolic acidosis, which results from

retention of endogenously produced acid. The serum bicarbonate concentration averages 17 to 18

mmol/L in uncomplicated cases. Hyperkalemia

may result from limited excretion and acidemia.

Potassium concentrations usually range from 5.0 to

6.5 mmol/L. Hyperphosphatemia occurs because

phosphate excretion is negligible. In the absence of

major tissue destruction, phosphate concentrations

rarely exceed 8 mg/dL. However, such levels, in

conjunction with the inhibition of the effect of vitamin D and the resistance to the actions of parathyroid hormone that occur in ARF,47 result in hypocalcemia. In the absence of obvious blood loss, the
Acute Renal Failure

719

hematocrit should fall over 5 to 7 days to a level of

0.23 to 0.27, and may reflect volume overload, covert blood loss, and bone marrow suppression.

Urinalysis

Biochemical and microscopical analyses of the

urine are extremely important in treating patients

with ARF, as the tests may provide evidence of

prerenal or postrenal azotemia, or may support the

diagnosis of established ARF. The patient with

prerenal azotemia should have concentrated urine

with high urine-to-plasma ratios of urea, creatinine,

and osmolality, and a low urinary sodium concentration. Similar values are found in patients with

acute urinary obstruction. The patient with established ARF usually loses the ability both to concentrate the urine and to conserve urinary sodium,

with low urine-to-plasma ratios of solute and high

urinary sodium concentrations. Similar values are

found in patients with ARF from chronic obstruction of the urinary tract. Indices of renal function

such as the fractional excretion of sodium and the

renal failure index are manipulations of these basic

data, all of which should be interpreted cautiously

if the patient has received diuretics in the 12 to 18

hours prior to their determination.48 Nonetheless,

biochemical analyses of urine can accurately distinguish between prerenal or postrenal failure and

established ARF in nearly 90% of cases.

The information gleaned from the microscopical

examination of the urine is so critical that the physician should examine it personally. The urine

sediment is typically relatively unremarkable in

prerenal and postrenal azotemia, although it may

contain hyaline and granular casts. Hematuria may

be present if a catheter is in place. Conversely, the

sediment in ARF contains many granular casts, and,

most importantly, renal tubular epithelial cells and

other cellular debris, which give rise to a very “dirty”

sediment. Experienced observers can distinguish

between prerenal or postrenal failure and established ARF on the basis of the sediment in approximately 85% to 90% of cases.

Radiographic Studies

Imaging of the kidneys in patients with ARF

should be limited to those studies that demonstrate

whether there are two kidneys, calculi, and urinary

tract obstruction. Although a technically well-done

renal ultrasound examination is the imaging test of

choice, ultrasound is not now available in the combat zone, and such capability may be limited even

further to the rear. Thus, plain radiographs of the

abdomen should be obtained, and may suffice to

determine the number of kidneys and to demonstrate radiopaque calculi. Because the renal shadows are often obscured by bowel gas, computed

axial tomography, which is available at fourth-echelon hospitals, is far superior and should be performed if the question of urinary obstruction cannot be resolved. Such scans should always be

performed without radiocontrast agents to avoid

further injury from these agents. Nuclear medicine

scans have virtually no role in the evaluation of the

patient with suspected ARF. In patients with true

anuria, selective angiography of the renal vessels

may be required to evaluate whether a vascular

catastrophe has occurred.

PREVENTION OF ACUTE RENAL FAILURE

There has been a resurgence of interest in preventing ARF in patients known to be at high risk

since, despite aggressive therapy, established ARF

remains associated with substantial mortality.

Moreover, advances in the understanding of the

abnormalities of cell biology that occur in ARF have

suggested avenues for new therapeutic regimens.

Finally, we have developed sufficient expertise to

be able to predict with some accuracy who is at risk

for the development of ARF. Prospective identification of high-risk patients should allow for

proactive intervention to prevent the occurrence of

ARF. This assumes that preventing ARF may be

more rewarding than improving the quality of care

of patients with established ARF.

Identification of High-Risk Patients

A number of investigators have conducted studies of patients with ARF and have identified clinical

scenarios in which patients are likely to be at high

risk for ARF. These studies have also shown that

ARF is almost always multifactorial (ie, it seldom

results from a single insult).

In 1983, S. H. Hou and her colleagues49 prospectively studied more than 2,000 consecutive hospital

admissions and found 129 episodes of ARF in 109

patients, for an incidence of 4.9%. She further

delineated those factors that appeared to be causal

in the development of ARF. Decreased renal perfusion accounted for 54 (42%) of the episodes. Among
Anesthesia and Perioperative Care of the Combat Casualty

720

the causes of decreased renal perfusion were volume depletion in 41%, cardiac dysfunction in 30%,

and sepsis in 19%. ARF developed postoperatively

in 23 patients (18%); however, only 12 of the patients

had documented hypotension. ARF in association

with cardiac and vascular surgery had incidence

rates of 15% and 8%, respectively. Administration

of radiocontrast agents was associated with ARF in

16 (12%) of the episodes, although such injury was

only rarely seen in patients who had normal serum

creatinine concentrations at the time the contrast

medium was administered. Aminoglycoside administration accounted for 9 (7%) of the episodes,

while miscellaneous causes, such as the hepatorenal

syndrome or unknown causes, were implicated in

27 (21%) of the episodes. Of particular interest was

the investigators’ inference that 55% of all episodes

were partly iatrogenic.

A similar analysis had been performed in 1982 by

H. H. Rasmussen and L. S. Ibels,50 who studied 143

patients with hospital-acquired ARF for the purpose of identifying risk factors and the nature of the

acute insults with which ARF was associated. The

presence of hypertension, preexistent renal disease,

and diabetes were the most prominent risk factors

associated with the development of ARF. Sepsis,

administration of nephrotoxins such as aminoglycoside antibiotics or radiocontrast agents, myoglobinuria from rhabdomyolysis, and volume depletion were the most common acute insults resulting

in ARF. The investigators noted that 48% of the

patients had more than one risk factor, and 62% had

more than one acute insult. More importantly,

analysis of the entire dataset demonstrated that the

number of acute insults was additive as a determinant of both the incidence and severity of ARF.

In research published in 1990, F. Jochimsen and

colleagues51 extended and expanded these observations in a prospective analysis of 261 patients who

had ARF and were in an intensive care unit. Two

groups of patients, 95 with ARF severe enough to

require dialytic support, and 166 patients whose

ARF did not require dialysis, were studied. Bleeding, volume depletion, sepsis, administration of

antibiotics, cirrhosis, and diabetes were identified

as the risk factors associated with more-severe ARF.

Patients with multiple risk factors were far more

likely to develop ARF than patients with a single

risk factor.

These studies, in conjunction with the clinical

experience of most nephrologists, reinforce the concept that patients without preexisting comorbidity

appear to be relatively resistant to the development

of ARF and may be able to withstand a single insult

without developing ARF. For example, uncomplicated gastrointestinal hemorrhage in otherwise

healthy patients rarely results in ARF.52 Likewise,

uncomplicated myocardial infarction is also infrequently associated with ARF.53

In victims of trauma, the nature of the injury in

large part determines whether the patient will be at

risk for the development of ARF. Thus, patients

who sustain only isolated limb or head injuries

rarely develop multiple organ failure and ARF.

Conversely, injuries to the abdomen, with or without other injuries, are accompanied by the development of ARF in a substantial number of patients.

In the conflict setting, casualties who develop

oliguria can be categorized into three groups. The

first consists of patients in whom relative or absolute hypotension has been present for varying times

before medical care is instituted. These patients are

frequently in shock. Resuscitative efforts may be

successful in restoring urinary output and renal

function. In such patients, the incidence and severity of renal dysfunction, manifested by oliguria and

prerenal azotemia, are functions of (a) how long the

renal insult has been present and (b) how efficacious are the efforts to restore effective circulatory

function. These patients are at high risk for subsequent renal injury, and every effort must be made to

prevent further ischemic or nephrotoxic injury.

The second group includes casualties who have

sustained severe and prolonged insults, for whom

resuscitative efforts have not been successful, and

in whom ARF has become established. The duration

or intensity of shock may have resulted in additional

ischemic injury to the brain, heart, gastrointestinal

tract, or liver. These patients may often require

surgery, and the presence of multiple organ failure

predicts substantial morbidity and mortality. Many

of these patients will require prolonged and aggressive nutritional and dialytic support.

The third group of casualties consists of those

who develop ARF while under medical care, during

or after initial evaluation, stabilization, evacuation,

and treatment. These patients may not be oliguric;

thus, ARF may be detected by biochemical analysis

of their blood. Hypotension may have been part of

their presenting picture, and sepsis may have been

associated with renal ischemia. Often these patients have undergone or will undergo surgery, or

require the administration of nephrotoxic drugs or

diagnostic agents. Renal injury may have to be

tolerated as part of the cost of effective treatment for

the casualty’s condition. A small fraction of this

group develop ARF because the urinary tract may

have been, or has become, obstructed.
Acute Renal Failure

721

While therapeutic efforts may differ somewhat

among these three groups, the basic principles of

the initial assessment of the patient with ARF are

applicable to all. Moreover, the information gained

from risk-factor identification and analysis, coupled

with an enhanced understanding of the pathophysiology of ARF, has provided opportunities for

proactive intervention to protect renal function.

Before examining methods of renal protection in

detail, we must first discuss volume expansion and

the pharmacological agents that are used in such

management strategies.

Volume Expansion

The beneficial effects of volume expansion have

been known for years. Although the mechanism or

mechanisms by which volume expansion abrogates

renal injury are not completely defined, at least four

mechanisms are thought to be operative. First,

volume expansion exerts a salutary effect on renal

hemodynamics by inhibiting intrarenal renin release, with a reduction in the concentration of

the vasoconstrictor angiotensin II. Second, it decreases the activity of the catecholamine-mediated

renal nerves by direct intranephronal mechanisms;

consequently renal blood flow is maintained.

Third, volume expansion results in a decrease in the

activity of the intrathoracic baroreceptors that play

a central role in the control of renal blood flow.

Diminution in their activity results in both decreased traffic in the renal nerves and minimal renal

vasoconstriction. The importance of these baroreceptors is illustrated by their role in hypotension

with cardiac failure. This situation, in which the

atrial baroreceptors are distended and less active

than when they are collapsed, results in a lesser

decrease in renal blood flow than does equivalent

hypotension from absolute volume depletion. And

fourth, some data suggest that saline may exert a

beneficial effect by inducing a solute diuresis, an

effect that may be independent of the renin-angiotensin axis.54

There is evidence that volume expansion can

reduce the incidence or severity of clinical ARF.

The reduction in the rate of ARF per seriously

injured casualty from the Korean War to the Vietnam War has been mentioned previously, and is

undoubtedly due in large part to rapid and aggressive volume resuscitation of casualties prior to their

transport to definitive medical care. Other evidence comes from studies of rhabdomyolytic-induced ARF. In 1979, F. Eneas, P. Y. Schoenfeld, and

M. H. Humphreys55 reported a salutary effect of

bicarbonate diuresis in patients with rhabdomyolysis. In other forms of ARF (eg, those induced

by cis-platinum and amphotericin), volume expansion with hypertonic saline or mannitol clearly results in attenuation of renal injury.56 However,

studies utilizing mannitol must be interpreted cautiously regarding the effects of volume expansion,

because the contribution of mannitol may be as a

volume expander, osmotic diuretic, or both.

In summary, volume expansion, usually done

with normal saline but occasionally with isotonic

fluids containing alkali or other base precursors, is

generally accepted as beneficial in the prevention of

ARF. This is particularly true if hypovolemia is

present, because interpretation of the numerous

studies examining the role of volume expansion in

the prevention or attenuation of ARF suggests that

volume expansion may prevent incipient ARF in

many situations of prerenal failure. A trial of volume expansion can be both diagnostic and therapeutic, in the sense that it can reduce the contribution that renal ischemia makes to the pathogenesis

of ARF. Moreover, a large body of clinical experience supports the concept that the volume-expanded

state confers protection against renal injury. This

concept has implications for fluid and nutritional

support of troops deployed to arid regions, in whom

subclinical volume depletion of several liters may

occur rapidly unless adequate salt and water are

provided. In such situations, maintenance of an

adequate extracellular volume may be the most

important mechanism by which ARF can be prevented.

Pharmacological Interventions

A number of agents have been evaluated in experimental and clinical studies for their ability to

abrogate or attenuate the untoward effects of

ischemia or nephrotoxins.57 Many of these have

been used in the management and, at times putatively, in the prophylaxis of ARF (Table 26-1). Most

studies with loop and osmotic diuretics and vasodilators have been conducted in either laboratory or

clinical ARF after the renal injury has been induced.

Newer agents—including dopamine, adenine nucleotides, calcium channel–blocking agents, atrial

natriuretic factor, and thyroid hormone—and agents

that (a) interfere with the generation of or (b) scavenge toxic free radicals have received much attention recently. This discussion concentrates on agents

that are presently in unrestricted clinical use, and

provides a brief overview of the rationale for the

use of the remaining agents.
Anesthesia and Perioperative Care of the Combat Casualty

722

TABLE 26-1

AGENTS USED IN THE PREVENTION OF

ISCHEMIC ACUTE RENAL FAILURE

Agent Status

Furosemide In use

Mannitol In use

Dopamine (low-dose) In use

Thyroid hormone Clinical trials

Adenine nucleotides Causes hypotension

Xanthine oxidase inhibitor Transplant trials

Free-radical scavengers Clinical trials

Calcium channel blockers Clinical trials

Prostaglandins Causes hypotension

Atrial natriuretic factor Used with dopamine

of incipient ARF to demonstrate whether furosemide

exerted a beneficial effect on renal function.60

The osmotic diuretic mannitol has long been

considered a renal protective agent, largely based

on studies such as those performed in 1961 by K. G.

Barry and colleagues,61 who utilized mannitol infusions prior to aortic cross-clamping in the operating

room and demonstrated preservation of renal blood

flow. Mannitol is a renal vasodilator and increases

tubular flow rate. In contrast to loop diuretics,

mannitol expands the extracellular fluid volume,

which may account for its beneficial effect in some

situations. It has also been shown experimentally to

prevent endothelial swelling associated with

ischemia.62 However, there has never been convincing evidence that it exerts a beneficial effect on

overall mortality if administered after ARF is established, and no controlled prospective studies utilizing mannitol early in oliguria (ie, in the initiation

phase of ARF) have been conducted. Nonetheless,

substantial uncontrolled clinical experience suggests that mannitol prevents ARF both in vascular

surgery procedures and in rhabdomyolysis.

Vasoactive Agents

A number of vasoactive agents have been utilized in various models of ARF and have been used

in a limited fashion in clinical ARF. These agents have

been used to promote renal vasodilation with the goal

of minimizing the adverse effects of renal vasoconstriction. Acetylcholine, vasodilatory prostaglandins,

antibodies to renin, and dopamine have all been

utilized. Although many laboratory studies have

shown that these agents can restore renal blood flow

toward normal values, only dopamine has been widely

utilized in clinical ARF because the other agents

have unacceptable hemodynamic toxicity.

Both experimental and clinical studies suggest a

beneficial role of dopamine in ARF, although in

clinical studies, proof of its efficacy is largely anecdotal. In 1979, A. Lindner and colleagues63 studied

the effects of dopamine with and without furosemide

in a canine model of nephrotoxic ARF. Treatment

with both agents resulted in improvement in both

renal blood flow and urinary flow rate, and attenuated the fall in glomerular filtration rate compared

with values in control animals or those animals who

received either dopamine or furosemide alone. In

contrast, in 1988, L. J. Pass and colleagues64 studied

the effects of dopamine with and without mannitol

in dogs undergoing thoracic aortic cross-clamping.

No beneficial effect on any measure of renal function was noted in any group.

Loop and Osmotic Diuretics

The use of loop diuretics (ie, a class of diuretic

agents that act by inhibiting reabsorption of sodium

and chloride in Henle’s loop) in both laboratory and

clinical ARF is based on three theoretical constructs.

First, furosemide is a renal vasodilator that might

contribute to the restoration or maintenance of renal blood flow in the presence of renal ischemia.

Second, loop diuretics also increase tubular flow

rate, potentially abrogating the effects of intratubular obstruction. Third, because the vast majority of renal oxygen consumption is utilized to reabsorb sodium, inhibiting sodium reabsorption by the

renal tubules should reduce renal oxygen consumption and renal work.

Furosemide has been shown in controlled clinical trials to promote urinary output in patients with

ARF.58,59 These trials contained small numbers of

patients, so their conclusions may be flawed. Nonetheless, many patients’ urinary output increased,

although neither the severity, duration, nor outcome of ARF was affected. A more problematic

issue is the role of furosemide in “converting”

oliguric to nonoliguric ARF. A substantial proportion of oliguric patients increase their urinary output when given furosemide. Whether this is due to

abrogation or attenuation of the severity of ARF, or

is simply a marker of those patients with reversible,

or intrinsically mild, ARF, is not known. No studies

have been conducted sufficiently early in the course
Acute Renal Failure

723

flow; and second, they provide the precursors necessary for injured cells to resynthesize ATP, levels

of which are markedly depressed after an ischemic

insult.68 Unfortunately, ATP-MgCl2 causes profound hypotension in humans, which severely limits its usefulness.

Other agents, such as calcium channel–blocking

agents and atrial natriuretic factor, have shown

promise in experimental ARF. Although a substantial

literature on the role of calcium channel–blocking

agents in ARF is available, it remains unclear

whether any beneficial effect is due to hemodynamic

effects or effects on intracellular redistribution of

calcium.69 These agents are currently undergoing

clinical trials.

The administration of thyroid hormone abrogates or attenuates renal injury in a variety of models of ARF.36 It appears to operate by increasing

either the activity or the amount of the tubular cells’

sodium-potassium ATPase. Thyroid hormone is of

interest for two reasons. First, it appears to be

relatively nontoxic and has few hemodynamic effects. Second, it appears to be effective even after

renal injury occurs. Clinical studies with this drug

are ongoing.

Finally, free radical scavengers (eg, superoxide

dismutase) and inhibitors of reactions that generate

free radicals (eg, allopurinol and deferoxamine)

have been subjects of intense investigation. As yet,

however, controlled clinical studies in patients with

ARF are not available. Allopurinol inhibits xanthine oxidase, which contributes to the generation

of toxic free radicals during reperfusion via the

Haber-Weiss reaction. Superoxide dismutase has

been demonstrated to be effective in preventing

ischemic damage in kidneys procured for organ

transplantation.70 Of interest is the fact that deferoxamine, an iron-chelating agent, substantially reduces the severity of ARF in glycerol models. Because iron participates in the Haber-Weiss reaction,

chelation of iron may reduce toxic free-radical

formation. Deferoxamine has been shown to minimize the untoward effects of such radicals on renal

function.71

Thus, many of the recent investigations into the

prevention of ARF have utilized agents that might

be beneficial, based on observations of the cellular

nature of injury induced by renal ischemia. Investigators have focused more on the response of individual cells or their constituents to injury than on

the whole organ’s response to injury. The use of

these agents may become widespread if efficacy can

be demonstrated in clinical trials. Some of these

experimental drugs are promising because of their

Regarding its use in clinical ARF, low-dose (ie,

renal dose) dopamine, 1 to 3 μg/kg/min, has been

administered in situations characterized by oliguria and incipient decreased renal function. In many

circumstances, dopamine is associated with a modest increase in systemic arterial pressure while urinary output increases. Whether the increase results

from the effect on systemic arterial pressure or from

intrarenal vasodilation cannot be discerned from

clinical studies. In 1982, R. F. Davis and colleagues65

studied (without control subjects) the effects of

low-dose dopamine in 15 adults with oliguria after

cardiac surgery. Dopamine infusion was associated with (a) improved creatinine and osmolar clearances, (b) improved urinary flow rate and sodium

excretion, and (c) reduced plasma renin activity,

when compared with such values in the patients

prior to administration of dopamine. Moreover, in

a prospective trial of patients undergoing liver transplantation, prophylactic dopamine was associated

with less ARF. In 1987, R. J. Polson and colleagues66

studied 34 patients who underwent 36 liver transplants. Nineteen patients (21 operations) received

low-dose dopamine prophylactically, while 15 patients did not. The incidence of renal dysfunction

was 9.5% in the dopamine group, compared with

67% in the control group. Overt ARF was not seen

in the dopamine group but was seen in 27% of the

control group. Dopamine is widely used in intensive care units in patients with oliguria or other

early signs of renal dysfunction. Although (a) the

effects of low-dose dopamine on renal function; (b)

the incidence or severity, or both, of ARF; (c) the

need for dialysis; and (d) mortality have not been

studied in a rigorous fashion, dopamine has been

associated with improvement in urinary output in

the majority of patients, with minimal toxicity. However, it should not be used in any patient whose

extracellular fluid volume is not adequate.

Experimental Drugs

A number of additional agents have shown promise in experimental ARF. However, there is limited

clinical experience with these agents, in some cases

because of their toxicity and in others because of

their relatively recent availability. Adenine nucleotides, generally in the form of adenosine triphosphate combined with magnesium chloride (ATPMgCl2), have been used extensively, and are of

interest because of their ability to attenuate the

severity of renal injury even when given after the

insult.67 Their mechanism of action may be twofold:

first, they result in a marked increase in renal blood
Anesthesia and Perioperative Care of the Combat Casualty

724

ability to exert beneficial effects even when administered after renal injury. It is likely that efficacy

will be linked to cytoprotective effects rather than

to effects on renal hemodynamics. A new generation of agents that may protect or restore renal

function after injury is exciting but unlikely to be

available for a few years for use in combat casualties

with ARF.

PROTECTION FOR PATIENTS IN INCIPIENT RENAL FAILURE

Patients with incipient or established ARF may

receive pharmacological therapy from our current

armamentarium for a number of different goals.

One goal is to promote urinary flow, with or without an improvement in glomerular filtration itself.

A second goal is to prevent the occurrence, or lessen

the severity, of ARF. Based on these goals, the

following protocol, for patients with acute oliguria

and for those at high risk for renal dysfunction, has

been developed.

Pharmacological Therapy of Acute Oliguria

As early as possible after oliguria ensues, the

extracellular fluid must be determined to be adequate—either clinically or by clinical impression

validated by the results of invasive hemodynamic

monitoring. If the extracellular fluid is not adequate, then normal saline, in 500-mL increments,

should be administered intravenously until either

the central venous pressure or the pulmonary capillary wedge pressure is higher than 15 mm Hg.

Then graded doses of 1, 5, and 10 mg/kg of furosemide are administered—at hourly intervals—to

clearly normovolemic patients. Furosemide will

often restore urinary output. If there is no response

to the 5-mg/kg dose, then 5 mg of metolazone, a

proximally acting diuretic, should be given 30 minutes before the 10-mg/kg furosemide dose is administered. If there is no response to this final

furosemide-metolazone challenge, then the patient

should be considered to be resistant to diuretics.

Resumption of urinary output at any dose of diuretic, however, obviates further doses. Low-dose

dopamine (1–3 μg/kg/min), which often promotes

urinary flow even without affecting systemic arterial pressure, is infused throughout the diuretic

challenge. In patients in whom oliguria is associated with rhabdomyolysis, or who have undergone

vascular surgical procedures with aortic crossclamping, or who have undergone cardiac bypass,

a mannitol-bicarbonate solution (100 g of 20% mannitol in 5% dextrose in water to which 3 ampules of

sodium bicarbonate have been added) can be used

to assist in restoring urinary output. Mannitol may

serve as a volume expander in these situations.

However, accurate assessment of the patient’s volume status is critical if mannitol is to be administered, as it may precipitate pulmonary edema in the

borderline hypervolemic patient. Mannitol should

not be used in patients with serum sodium concentrations lower than 125 mmol/L: life-threatening

hyponatremia may ensue as mannitol causes water

to move from the cells into the extracellular fluid.

Neither furosemide nor dopamine is likely to be

effective, and the former may be harmful if the

patient is volume depleted; thus, the extracellular

fluid must be adequate.

Concomitant with the measures described above,

an indwelling bladder catheter should be placed,

or the existent catheter should be flushed. A renal

ultrasound examination should be obtained

emergently. Ultrasound equipment will not be

available in field medical treatment facilities, but

integrity of the bladder catheter should be ensured

in all patients.

Prevention of Acute Renal Failure in High-Risk

Patients

The same protocol can be used in patients at high

risk for developing oliguria or established ARF or

both. Many of these patients will need to undergo

surgery imminently, and some will have undergone surgery recently. One standard practice is to

obtain baseline measures of renal function (ie, a

current BUN and creatinine concentration) and a

urinalysis. An expanded extracellular fluid should

be maintained in these patients, either as determined on clinical grounds or, preferably, with some

form of hemodynamic monitoring. For patients

who will undergo vascular procedures, a portion of

administered fluids should include mannitol 1 g/

kg, given as a 20% solution. Maintenance of an

expanded extracellular fluid is probably the most

powerful protection against renal ischemia associated with alterations in systemic arterial pressure

from the adverse hemodynamic effects of anesthesia and blood loss during surgery.

In oliguric patients and in those at high risk for

renal injury, potentially nephrotoxic drugs should

be used judiciously. Loading doses of drugs are not

altered, but the use of known nephrotoxins should

be modified by either prolonging the dosing inter-
Acute Renal Failure

725

EXHIBIT 26-3

CAUSES OF RHABDOMYOLYSIS

Trauma

Electrolyte Disorders

Hypokalemia

Hypophosphatemia

Myopathies From Enzyme Deficiencies*

Phosphorylase deficiency (McCardle’s

disease, ie, type 5 glycogenosis)

Phosphofructokinase deficiency (Tarui’s

disease)

Carnitine palmityl transferase deficiency

Myopathies From Toxins*

Alcohol-induced myopathies

Carbon monoxide–induced myopathies

Idiopathic Paroxysmal Myoglobinuria*

*Not discussed in this chapter

val or giving reduced doses at regular intervals.

Renal function should be assessed by measuring the

serum creatinine at least daily. Since measurement

of drug levels will not be available in battlefield

medical treatment facilities, some nephrotoxic injury is likely. Other drugs, particularly nonsteroidal antiinflammatory agents that are useful as analgesics, should be used with caution; alternative

analgesics are available.

To illustrate these principles, medical officers

should consider the following discussion, which

describes a situation that occurs frequently in combat and is likely to lead to ARF. Rhabdomyolyticinduced ARF, a classic example of posttraumatic

ARF,72 commonly occurs after a missile or crush

injury of an extremity (as a result of a compartment

syndrome) or with heat stroke. Even though there

are a number of nontraumatic causes of rhabdomyolysis (Exhibit 26-3),73 this discussion is confined

to the traumatic causes, as they are likely to be

encountered in battle injuries.

Muscle necrosis results from direct trauma or

from the impairment of the blood supply. Muscle

cells depend on oxygen delivery to maintain their

cellular integrity. As ischemic injury occurs, muscle

cells swell and eventually lyse. The release of intracellular contents causes predictable alterations in

blood chemical values, and, with sufficient severity, leads to ARF or death. Muscle contains myoglobin, a respiratory protein that contains a globin

chain and a heme moiety. The latter contains iron

and is the delivery system for oxygen for the muscle

cells. Myoglobin is carried in the circulation loosely

bound to an α2 globulin up to a concentration of

approximately 23 mg/dL; if this concentration is

exceeded, myoglobin circulates freely. As the molecular weight of myoglobin is 17,000 daltons, it is

readily filtered by the glomeruli. In normal individuals, myoglobin is excreted if urinary flow rates

and pH are optimal. One gram of muscle contains

4 mg of myoglobin.

However, there are situations that preclude the

uneventful excretion of myoglobin. These situations include volume depletion and acidic urine. If

sufficient quantities of myoglobin reach the kidney

in the presence of these conditions, ARF is likely to

occur. Volume depletion contributes to the toxicity

of myoglobin via four mechanisms:

1. Renal blood flow is reduced, and the kidneys are subject to ischemic injury, with

the consequences that have been discussed

previously.

2. The relatively low urinary flow rates associated with volume depletion serve to increase the concentration of myoglobin in

the tubules. Myoglobin precipitates with

low-molecular-weight proteins in tubular

fluid, which obstructs the tubular lumen,

preventing flow.

3. In acidic urine, myoglobin dissociates into

two moieties: globin and ferrihemate. This

latter substance is extremely toxic to renal

tubular cells.74

4. When ferrihemate is transported into cells,

iron is released. When reperfusion occurs, the

iron is a source of toxic free radicals through

the Haber-Weiss and Fenton reactions.

ARF induced by rhabdomyolysis is one of the

most severe forms of ARF. A substantial portion of

patients who sustain muscle injury sufficient to

induce ARF die of shock or hyperkalemia. The

latter results from the release of intracellular potassium, the concentration of which in muscle is approximately 140 mmol/L. Other intracellular products released include organic acids; purine precursors such as uric acid; creatine, which is ultimately dehydrated into creatinine; other muscle

enzymes; and proteins, which serve as procoagulants on their release.
Anesthesia and Perioperative Care of the Combat Casualty

726

Patients with rhabdomyolytic ARF present with

overt trauma; oliguria or anuria; hypotension; and

severe biochemical abnormalities, including hyperkalemia, metabolic acidemia, hyperphosphatemia,

hypocalcemia, hyperuricemia; and elevations of enzymes principally found in muscle, particularly creatine kinase. Renal failure develops quickly as a

consequence of both renal ischemia (from shock) and

the nephrotoxicity of myoglobin. The profound depression of glomerular filtration, in conjunction with

an excessive catabolic rate and the release of creatine

from damaged muscle, results in a creatinine concentration that is disproportionately elevated compared

with the BUN concentration. Moreover, the rate of

production of creatinine continues to be excessive as

long as damaged muscle is present; thus, the daily

increment in the serum creatinine concentration may

exceed 4 to 6 mg/dL.

The prevention of rhabdomyolytic-induced ARF

follows logically from an understanding of its pathogenesis. First, volume depletion must be corrected

rapidly and the extracellular fluid should be expanded. Casualties who sustain crush or other

injury of an extremity are often in shock, and may

lose liters of extracellular fluid into the injured

extremity. In situations where muscle groups are

enclosed by nondistensible fascial planes, such

swelling may contribute to further muscle necrosis.

Nonetheless, volume depletion and shock must be

treated aggressively in an effort to correct renal

ischemia. Renal blood flow must be restored before

attempts to augment urinary flow can be made.

Tubular flow can be enhanced by expansion of

the extracellular fluid with mannitol. In addition to

its effects on renal blood flow owing to its ability to

expand the extracellular fluid, mannitol is also an

osmotic diuretic and will increase bulk fluid flow

through the tubules. This effect serves to enhance

the excretion of myoglobin and to restore tubular

patency. Alkalinization of the urine is also crucial.

Because myoglobin dissociates into its toxic components in an acidic milieu, prevention of further

dissociation is facilitated by infusing isotonic sodium bicarbonate at rapid rates. This fluid, in

addition to serving as a urinary alkalinizing agent,

is also an effective volume expander. Low-dose

dopamine infusion, even in the presence of normal

blood pressure, should be started.

The aggressive character of this form of ARF

usually necessitates early and vigorous hemodialysis if renal resuscitation is unsuccessful.75 These

casualties are extremely catabolic, and hemodialysis

should be applied early, before the plasma concentrations of potassium or nitrogenous waste result in

cardiac death or uremia, respectively. Additionally, surgical expertise is required to determine the

extent of surgical debridement necessary, and

whether and when fasciotomies should be performed. Because limb salvage is secondary to preservation of life, fasciotomies should be utilized liberally—certainly if there is any question about the

vascular integrity of a limb.

Despite protective and resuscitative efforts, however, many patients will not respond to the maneuvers outlined above, and are assumed to have established ARF. We must then determine clinically

whether conservative or dialytic therapy is indicated. Part of such determination includes an assessment of the optimal timing and type of dialysis,

should it be required. Because the fundamental

assumption in the treatment of ARF is that injured

kidneys can recover, the major goal of therapy is to

support the patient until this occurs. An ancillary

goal is to provide an optimum milieu for both

nutritional support and prevention or treatment of

infection (infection being by far the major cause of

death in ARF). To these ends, the assistance of

experts in nutritional care and infectious diseases is

critical in the management of these patients. Two

management strategies can be used for patients

with established ARF: conservative management

and management with some form of dialysis. Many

of the principles of conservative management of

course also apply to patients who require dialysis.

Some patients with ARF, particularly those who

remain nonoliguric and in whom catabolism is not

excessive, can be managed without dialysis. Conservative management requires meticulous attention to nutritional support, fluid and diuretic

therapy, and acid–base and electrolyte balance, the

use of drugs, and general medical care.

Nutritional Support

The subject of nutritional support in ARF was

reviewed in 1994.76 One of the seminal studies that

supported the use of nutritional support in ARF

was conducted in 1967 by H. A. Lee, P. Sharpstone,

and A. C. Ames.77 These investigators studied 45

patients with ARF who were treated with casein

CONSERVATIVE TREATMENT OF ESTABLISHED ACUTE RENAL FAILURE
Acute Renal Failure

727

hydrolysate and lipid, and noted diminished weight

loss and more prompt recovery of renal function.

Then in 1973, R. M. Abel and colleagues78 prospectively studied 53 patients with ARF. These investigators utilized a combination of hypertonic dextrose and essential amino acids, compared with

glucose alone, in cohorts of 28 and 25 patients,

respectively. Of the patients receiving the proteinglucose solution, 75% recovered from ARF, compared with 44% of the patients receiving glucose

alone (P < .02). Of the patients who required dialysis, 65% of those given amino acids and glucose

survived, while only 18% of those given glucose

alone survived.

In 1975, S. M. Baek, G. G. Makabali, and C. W.

Bryan-Brown79 studied 129 patients with postoperative ARF and noted a reduction in mortality

from 70% in patients given glucose alone to 46% in

patients treated with amino acids. The improvement in mortality was particularly impressive in

patients who had sepsis.

However, the results of a number of other studies

of nutritional support of patients with ARF have

not been consistently positive, and the optimal nutritional regimen has not yet been defined. Moreover, no studies have been conducted in prospectively defined groups in which disease etiology and

severity have been stratified. Nonetheless, many

investigators believe that nutritional support of

patients with ARF is beneficial, and it is often provided to patients.

A large body of clinical experience suggests that

most fluid administered to patients with ARF should

be nutritionally supportive, because these patients

have limited ability to excrete fluids. All fluids

should be administered only as they meet a specific

need of the patient, and “maintenance fluids” should

be carefully prescribed. Nutritional support should

be initiated within the first 48 hours after the injury

in most patients with posttraumatic ARF, because

nutritional support clearly attenuates the hypercatabolism that many of them exhibit.

Fluids used to provide nutritional support

(the “renal-failure” fluids) consist of hypertonic

glucose and amino acid solutions, and should

be supplemented by lipid emulsions to provide

additional calories. Energy requirements are best

calculated on the basis of basal metabolic requirements, with additional requirements predicated

on a stress factor related to the type and severity of

the underlying illness. Energy requirements (ER)

in kilocalories per day can be expressed in the

formula

ER = basal requirements • stress factor

A factor of 1.25 accounts for the increased energy

requirements of ill patients who are not paralyzed.

The stress factor is 1.30 to 1.50 for patients who have

sustained multiple trauma or who have infection.80

Basal metabolic requirements and stress factors are

discussed in detail in Chapter 23, Metabolic Derangements and Nutritional Support.

In general, a minimum of 30 to 50 kcal/kg/d is

required by most critically ill patients. Carbohydrate should account for 60% to 70% of the calories,

while most of the remainder should be provided as

fat. Excessive carbohydrate administration will

cause carbon dioxide accumulation and respiratory

distress; thus, judicious use of lipid emulsions is

critical.81 Fluid regimens should provide as many

calories in as small a volume as possible; thus, 50%

to 70% dextrose is often required. Lipid can be

administered through a peripheral vein, as the solutions are not hypertonic.

Because of azotemia, the quantities of protein

must be limited to 0.8 to 1.0 g/kg/d unless the

patient is on dialysis. Amino acids are lost across

the dialysis membrane at a rate of 10 to 15 g per

treatment, and must be replaced in addition to the

basal requirement of amino acids.82 Protein should

be of high biological value and contain mostly essential amino acids, including branched-chain amino

acids. Solutions containing casein hydrolysates or

amino acid preparations in which nonessential

amino acids predominate may result in excessive

azotemia without attenuation of catabolism.

Enteral alimentation is preferable to parenteral

alimentation if the patient’s condition permits.

Small-diameter polyethylene feeding tubes are

placed through the patient’s nose for instillation of

solutions of either essential amino acids or a mixture of essential and nonessential amino acids. Not

only is enteral feeding associated with fewer complications, but some evidence also suggests that

feeding facilitates the maintenance of the integrity

of the bowel mucosa, which may prevent endotoxemia and gut-associated sepsis, both of which

can induce multiple organ failure.83 Moreover, the

presence of nutrients in the bowel will maintain the

enzymes necessary for enteral nutrition and permit

a smooth transition to enteral feedings when the

patient’s condition permits. However, enteral solutions will often cause diarrhea if administered in

too large quantities or at too rapid a rate. The use of

infusion pumps, which facilitate constant instillation of solution, greatly reduces this complication.
Anesthesia and Perioperative Care of the Combat Casualty

728

Fluid and Diuretic Therapy

Fluid intake should be limited to the measured

urinary output, with additional fluid given for measured gastrointestinal losses and estimated insensible losses. As has been emphasized previously,

much of the administered fluid should be nutritionally supportive; the remainder is often required for

medication administration. As a general rule, all

medications should be administered in as concentrated a form as possible. Most nonoliguric patients

excrete no more than 1 to 1.5 L of urine per day. This

loss, coupled with gastrointestinal and insensible

losses, may be sufficient to allow required fluids in

the form of nutrition and medications to be administered. Because most patients excrete urine that is

hypotonic to plasma, with urinary sodium concentrations of 60 to 90 mmol/L, fluid that is equivalent

in electrolyte composition should be administered.

Replacement of urinary fluid and electrolyte losses

in this fashion will tend to minimize water excess or

deficit and avoid hyponatremia or hypernatremia,

respectively. The serum sodium concentration

should be monitored frequently as a guide to the

patient’s water balance, and should kept in the

range of 130 to 150 mmol/L.

Ideally, the patient treated conservatively will

lose no more than 0.5 to 1.0 kg of body weight per

day. However, some nonoliguric patients will not

excrete sufficient urine to allow for effective nutritional support, particularly if large quantities of

other fluids (eg, antibiotics) must be administered,

and they will gain weight. In such patients, urinary

output can be augmented, if necessary, with low-dose

dopamine infusions and intermittent doses of loop

diuretics. There appear to be few adverse effects of

low-dose dopamine infusions. However, excessive

use of loop diuretics may result in metabolic alkalemia,

deafness, and potassium depletion, the latter of

which results in impairment of glucose homeostasis

and proper muscle function. Osmotic diuretics such

as mannitol should be avoided in most patients with

established ARF, as they can induce hyponatremia

if a diuresis does not result, hypernatremia if excessive free-water diuresis is induced, or pulmonary

edema if urinary output declines. Thiazide diuretics are not effective in ARF, and potassium-sparing

diuretics are contraindicated.

Management of Acid–Base Disturbances

The major acid–base disturbances that occur in

patients with ARF are metabolic alkalosis and metaHowever, many patients with posttraumatic ARF

will have undergone abdominal surgery, and enteral feedings will not be possible. Moreover, the

magnitude of nutritional support required by

hypercatabolic patients often precludes the use of

enteral feedings. Should total parenteral nutrition

(TPN) be required, access to the central circulation

is obtained through the subclavian or the internal or

external jugular veins. The catheter site should be

inspected and redressed daily, using strict aseptic

techniques, and the catheter used exclusively for

TPN. If these guidelines are followed, catheterrelated infection is uncommon.

The composition of enteral or parenteral fluid

can be varied according to the needs of the patient.

Sodium can be added or deleted depending on the

volume status and the serum sodium concentration. Often, sodium is administered as the acetate

salt; the eventual metabolism of acetate to bicarbonate tends to abrogate the acidemic effects of TPN

solutions. Potassium supplementation is seldom

required initially, but is generally required after

several days of TPN when the rate of catabolism has

slowed and anabolism has begun. The serum phosphate concentration is high initially but can fall to

dangerously low levels after several days of therapy,

and may require addition of phosphate to the TPN

as either the potassium or sodium salt.

The success of nutritional support in patients

with ARF depends on

• avoidance of infection in patients treated

with TPN,

• attenuation of catabolism,

• establishment of relatively normal biochemical values in plasma, and

• maintenance of stable extracellular fluid.

A standard monitoring scheme should be followed,

so that electrolyte disturbances can be anticipated

and corrected before they become severe. The serum glucose should be monitored several times

daily, and hyperglycemia should be treated with

insulin. Although patients with renal dysfunction

have prolonged serum half-life of insulin, they also

exhibit insulin resistance. In general, insulin administration is required in virtually all patients

treated with TPN. Once daily insulin requirements

have become stable, the requisite amount of insulin

can be administered in the TPN solution by constant infusion. Surveillance of glucose levels should

be continued, however, as sudden hyperglycemia is

often the first sign of an incipient infection.
Acute Renal Failure

729

bolic acidosis. The more immediate threat is from

metabolic acidosis, which results from both excessive generation of acid and the inability to excrete

acids. Metabolic alkalosis usually results from inadequate replacement of nasogastric fluid losses,

particularly in nonoliguric patients, in whom chloride, and to a certain extent, potassium, loss represents the primary pathophysiological mechanism.

Metabolic Acidosis

Metabolic acidosis is manifested by a depressed

serum bicarbonate concentration and, usually in

posttraumatic ARF, an anion gap. The concentration of lactic acid is often elevated in these patients,

as are concentrations of other organic acids (such as

from phosphate and sulfate salts) when renal failure is severe. In uncomplicated cases of ARF, the

serum bicarbonate concentration will average 16 to

18 mmol/L, and the serum pH will average 7.34 to

7.37. This degree of acidemia is not associated with

untoward effects. In fact, the rightward shift of the

oxyhemoglobin curve will result in more effective

oxygen delivery to tissue. If acidosis is more severe,

cardiovascular complications such as arrhythmias

and hypotension may ensue.

The treatment of metabolic acidosis is relatively

simple,84 although recent questions have been raised

regarding the efficacy of bicarbonate administration in correcting the hemodynamic abnormalities

in critically ill patients.85 Nonetheless, nonoliguric

patients can receive sufficient alkali, usually in the

form of sodium bicarbonate, to correct their base

deficit and ongoing losses. In patients who are not

excessively catabolic, such ongoing losses should

amount to approximately 1 mmol HCO3/kg/d. In

certain patients, the alkali requirement can be met

with oral preparations. Sodium bicarbonate tablets, however, result in excessive eructation. A

combination of citric acid and sodium citrate (Sholl’s

solution), which contains 1 mmol HCO3 equivalent

per milliliter, can be used. In severe cases, hemodialysis can be used to remove extracellular fluid

volume so that sodium bicarbonate can be administered in large quantities. The concentration of bicarbonate or equivalent base in the dialysate can be

manipulated to meet the needs of the patient.

Metabolic Alkalosis

Metabolic alkalosis is characterized by an elevated serum bicarbonate concentration and a depressed serum chloride concentration. The actual

pH of the blood depends on whether (a) the alkalosis

is an isolated acid–base disturbance or (b) there are

other disturbances. Substantial alkalosis has a number of untoward effects, including

• hypokalemia, which can result in muscle

weakness and cardiac arrhythmias;

• respiratory muscle weakness, which may

retard successful weaning from the ventilator;

• compensatory respiratory acidosis, because

the response to pure metabolic alkalosis is

to retain carbon dioxide, and patients on

assisted ventilation may become acidotic in

an attempt to return the alkaline pH toward more normal values;

• arterial hypoxemia, which is the result of

the alveolar hypoventilation required to

produce hypercarbia; and

• impaired oxygen delivery to tissues, because the oxyhemoglobin dissociation curve

is shifted to the left, for any given partial

pressure of oxygen; therefore, less oxygen

is delivered to tissue.

Metabolic alkalosis is largely preventable, particularly if intravascular volume (sodium chloride)

and potassium depletion are avoided. Excessive

diuretic-induced volume and electrolyte losses

should be replaced. Moreover, because nasogastric

suction removes volume, potassium, and acid from

the body, inhibition of gastrointestinal acid secretion by histamine-receptor blocking agents will reduce net proton loss from the body. In this regard,

ranitidine is preferable to cimetidine, since alterations in mental status are seen more frequently

with the latter.

The treatment of established metabolic alkalosis

includes correction of both intravascular volume

deficits and potassium depletion. Potassium deficits can be substantial, on the order of several hundred millimoles. In the rare situation in which

volume and potassium repletion do not correct

alkalosis, carbonic anhydrase inhibitors can be used

to promote urinary bicarbonate loss. However, in

the vast majority of patients with ARF, these drugs

will be ineffective. In oliguric patients, the volume

space for correction of volume deficits may not

exist. Thus, dilute hydrochloric acid can be infused

into a central vein in nonoliguric patients or into the

venous return of a dialyzer in patients on dialysis.86

With this therapy, the difference between the measured and the desired serum chloride concentration
Anesthesia and Perioperative Care of the Combat Casualty

730

levels of hyperkalemia that are tolerated by

patients with chronic renal failure.

The causes of hyperkalemia in ARF include minimal urinary excretion (fecal excretion is possible,

but takes days) and release of potassium ions from

injured tissue. In addition, hyperkalemia is aggravated by metabolic and respiratory acidemia and

insulin resistance; and is worsened by the presence

of drugs with potassium effects (eg, nonsteroidal

antiinflammatory drugs, extravascular influsion

drugs).

Determining the mechanism of hyperkalemia may

assist the physician in choosing the most appropriate therapy, because hyperkalemia can be controlled

with exchange resins, glucose and insulin, and bicarbonate. The most important therapy, however,

is that which antagonizes the effect of hyperkalemia

on cardiac muscle. Thus, the initial diagnostic maneuver after hyperkalemia is first noted is to obtain

an electrocardiogram. If there are any abnormalities, calcium chloride should be administered immediately. Then, more definitive steps can be taken

to resolve the problem.

Phosphate Abnormalities

Hyperphosphatemia is the most common abnormality of divalent ion metabolism in ARF and can

usually be controlled by the frequent oral administration of aluminum-containing antacids, either aluminum hydroxide or aluminum carbonate. These

agents are administered as suspensions, 30 to 60 mL

every 3 to 4 hours, until the serum phosphate concentration approaches normal values, after which

they can be administered less frequently. Although

such agents bind phosphorus most effectively in the

stomach (ie, when given with food), they are effective even in the absence of enteral nutrients, in

which situation they interrupt the enteric recirculation of phosphorus. Aluminum toxicity should not

be considered a problem in patients with ARF, as it

is in those with chronic renal disease. Aluminumcontaining antacids are often ineffective until they

have been administered for several days. Even

then, they may not control the serum phosphate

concentration, in which case sucralfate can be administered four to six times daily in doses of 1.0 g.

Finally, hyperphosphatemia almost always responds to the provision of adequate nutrition,

particularly if appropriate concentrations of

branched-chain amino acids and effective nonnitrogen-to-nitrogen caloric ratios are met. Presumably, effective nutritional support retards catabois multiplied by the product of the body weight (in

kilograms) and 0.27 (the volume of distribution of

chloride). The amount of chloride, in milliequivalents, is administered as an equal amount of 1.0 N

hydrochloric acid diluted in dextrose and water.

Finally, hemodialysis utilizing especially prepared

dialysate solutions can remove excessive bicarbonate and replace potassium and sodium chloride

losses.

Management of Electrolyte Imbalances

Hyperkalemia

Hyperkalemia is potentially the most dangerous

of all metabolic complications of ARF, as lethal

cardiac dysrhythmias can result with little warning. Hyperkalemia results from a number of different mechanisms, including the following:

• Transcellular shifts of potassium for hydrogen occur during metabolic acidemia,

when the body attempts to buffer protons

intracellularly. Although it has been classically taught that for each 0.1 change in the

pH, there is a reciprocal 0.6 mEq change in

the serum potassium concentration, some

researchers87 now think that this does not

occur when the metabolic acidosis is due to

organic (ie, lactic) acid accumulation.

Rather, transcellular shifts occur only when

hydrogen is accompanied by an anion such

as chloride, which is restricted from

transcellular movement.

• Excessive production of potassium also

occurs when there is breakdown of tissue in

conjunction with inability to excrete potassium. Tissue destruction is common in

rhabdomyolysis, but may also be seen with

ischemia of the gastrointestinal tract and

after vascular surgery, in which tissue viability may be in question.

• Interference with potassium excretion by

drugs may also occur. Nonsteroidal agents

and β-adrenergic blocking agents may interfere with and impair renal excretion of

potassium.

• Finally, renal dysfunction itself severely

limits the ability to excrete potassium. Although fecal potassium excretion often increases by as much as 35% in patients with

chronic renal failure, this adaptive mechanism is unusual in ARF, and is probably

why patients with ARF do not tolerate the
Acute Renal Failure

731

lism and promotes anabolism, so that phosphorus

is transported into cells.

Hypophosphatemia has a number of untoward

effects, the most common of which are (a) impaired

muscle function and (b) reduced extraction of oxygen from hemoglobin.88 The most frequent adverse

clinical effect is diffuse muscle dysfunction, which

may involve both skeletal and cardiac muscle.

Skeletal muscle dysfunction may severely retard

efforts to wean the patient from the ventilator. Moresevere hypophosphatemia can result in rhabdomyolysis. The second-most-frequent effect is a

shift in the oxyhemoglobin dissociation curve, so

that less oxygen is delivered at a given partial pressure. Other effects of hypophosphatemia on the

hematopoietic system include (a) hemolytic anemia

due to red blood cell ATP depletion and the inability to maintain membrane fluidity and (b) white

blood cell dysfunction.

Hypophosphatemia in ARF is commonly a consequence of overaggressive therapy of hyperphosphatemia, and it occasionally occurs in patients who have received TPN. The serum

phosphorus can be expected to fall 0.3 mg/dL/d in

patients who are receiving TPN. Thus, patients

who have baseline normal phosphate concentrations can be expected to develop significant

hypophosphatemia in 5 to 10 days. When hypophosphatemia develops, phosphorus should be

added to the TPN solution. Symptomatic hypophosphatemia is common when the serum phosphate

concentration is below 1.8 mg/dL. In such situations, replenishment of phosphate stores should be

considered. Phosphate repletion can be accomplished by a number of different maneuvers.88

Calcium Abnormalities

Hypocalcemia results not only from hyperphosphatemia but also from resistance to the actions of vitamin D and parathyroid hormone. Unless the patient is symptomatic, has signs such as

Chvostek’s sign, or has electrocardiographic changes

associated with hypocalcemia, the more judicious

initial treatment is to lower the elevated serum

phosphate concentration toward normal. As the

serum phosphate concentration becomes more normal, the serum calcium concentration will begin to

rise. If necessary, elemental calcium can be administered as enteral or parenteral nutritional supplements. Should clinical symptoms or electrocardiographic changes consistent with hypocalcemia

become evident, calcium should be administered

intravenously. There are a number of preparations,

including the chloride, lactate, or gluceptate salts,

that can be utilized.

APPROACHES TO DIALYSIS

achieved and then maintained with a 3- to 4-hour

treatment conducted three to five times weekly.

Modern artificial kidneys achieve BUN and creatinine clearances in excess of 175 mL/min and have

ultrafiltration rates of 4 to 5 milliliters per millimeter of transmembrane pressure per hour. With

typical operating parameters, BUN and creatinine

concentrations can be reduced by 30% to 40%, and

2 to 3 L of extracellular fluid can easily be removed

during a 4-hour treatment. Many modern dialysis

membranes are made of cuprophane, a substance

that may occasionally induce hypoxemia in the

initial period of the dialysis treatment by activating

components of the complement cascade, resulting

in stasis of leukocytes in the pulmonary circulation.

Although alternative materials for dialysis membranes are available, they are associated with excessive clotting in the artificial kidney. Fortunately,

the hypoxemia associated with cuprophane membranes is transient. The cuprophane membrane is

configured in either parallel-plate or hollow-fiber

geometry. Although parallel-plate membranes are

easier to use, they are associated with slightly higher

Conservative therapy of ARF requires meticulous management, and attention to the routine details of patient care requires considerable effort.

However, the severity of renal dysfunction, with its

resultant catabolism and metabolic perturbations,

may eventually require dialysis support. Thus,

when or if conservative management is inappropriate or unsuccessful, dialysis is indicated. Three

approaches to blood-purification therapy can be

utilized to attenuate the effects of nitrogenous waste

retention, electrolyte imbalance, and circulatory

overload: conventional hemodialysis, peritoneal

dialysis, and hemofiltration.89

Conventional Hemodialysis

Hemodialysis has traditionally been the therapy

of choice for posttraumatic, hypercatabolic ARF,

and has been designated as the mainstay of renal

replacement therapy in the DEPMEDS doctrine.

Removal of urea nitrogen, creatinine, other retained

waste products, potassium, sodium, and water is

efficient, as metabolic homeostasis can usually be
Anesthesia and Perioperative Care of the Combat Casualty

732

1. The blood pump generates blood flow that

is independent of the patient’s blood pressure.

2. The efficiency of solute removal with

hemodialysis induces osmolar shifts, which

are thought to induce hypotension.

3. The use of acetate as a base replacement in

the dialysate can result in peripheral vasodilation and impaired myocardial contractility, particularly in patients with liver

dysfunction who cannot rapidly metabolize acetate to bicarbonate (this has been

abrogated by the virtual universal use of

bicarbonate dialysate in critically ill patients).

Anticoagulation of the blood with heparin is

generally required, although there are several alternatives to conventional anticoagulation if bleeding is a risk.90 There is substantial experience utilizing the technique of heparin-free dialysis, in which

the artificial kidney is flushed with saline several

times each hour. Unfortunately, this not only

dramatically reduces the efficiency of the dialysis

procedure, it also limits the amount of fluid that can

be removed in a standard treatment period. The

judicious use of low doses of heparin is associated

with acceptable patency of the extracorporeal circuit without untoward bleeding. In general, we

should administer 15 units of heparin per kilogram

of body weight as a loading dose, then 750 to 1,000

units per hour as a constant infusion. Either dose is

easily alterable, depending on the level of

anticoagulation, which is measured by the activated clotting time using a portable monitor and

disposable tubes coated with platelet activating factor. The desired end point of the test is between 160

and 180 seconds, and this method allows for rapid

and repetitive assessment of the effects of heparin

administration. Such techniques as regional

anticoagulation with heparin or citrate, with protamine or calcium rescue respectively, or anticoagulation with prostacyclin, largely have been abandoned. Prostacyclin produces severe hypotension,

which makes maintenance of the extracorporeal

circuit impossible.

Sorbent-Based Dialysis Delivery System

The large water requirements of conventional

hemodialysis can be avoided by the use of sorbentbased dialysis delivery systems.91 These systems

regenerate spent dialysate, and require approxirates of clotting than are the hollow-fiber type.

Polyethylene tubing to conduct blood flow to and

from the artificial kidney is required and must be

compatible with both the artificial kidney and the

dialysis machine.

Hemodialysis operates through a combination of

diffusive and convective transport. Solute removal

by diffusion depends on the size of the solute molecules; the thickness and surface area of the artificial membrane; and the rates of blood and dialysate

flow, which are countercurrent to each other. Solute removal by convection depends on the rate of

fluid (ie, solvent) transport across the membrane.

Fluid removal depends on a pressure gradient across

the membrane, which is generated by a combination of the patient’s blood pressure and resistance to

blood flow through the angioaccess, and pressure

applied from the dialysate side of the membrane.

This cumulative pressure, known as the transmembrane pressure, can be varied by the operator to

enhance or retard fluid removal.

Circulatory Access

Obtaining access to the circulation for hemodialysis is often quite difficult in critically ill patients. Hemodialysis requires a blood flow of at

least 200 to 250 mL/min, which is generated through

the use of a blood pump intrinsic to the dialysis

machine. Angioaccess is typically achieved with

double-lumen dialysis catheters, which are placed

percutaneously in the subclavian, internal jugular,

or femoral vein. The first location is preferable,

since an occlusive bandage can easily be applied to

prevent contamination. These catheters should be

dressed only by dialysis personnel, and are routinely left in place for several weeks. Catheterrelated infection is extremely rare if the catheters

are used only for dialysis. Percutaneous access for

conventional hemodialysis is preferable to arteriovenous shunts: the latter must be placed surgically

and are often complicated by infection and bleeding. Recently, double-lumen catheters that have a

synthetic polyester cuff have been used with some

success. These catheters are surgically placed in the

subclavian vein, where their properties are equivalent to those of conventional percutaneous catheters. However, for rapid access to the circulation

for dialysis, we prefer the percutaneous approach.

Although some patients with ARF tolerate

hemodialysis without problems, hemodynamic instability and hypotension are relatively common

for at least three reasons:
Acute Renal Failure

733

mately 6 L of water, as opposed to the nearly 250 L

of water required by conventional hemodialysis.

Bicarbonate, calcium, potassium, and other desired

solutes can be added to the dialysate as needed.

Waste products that diffuse from the blood into the

dialysate are adsorbed onto different layers of a

sorbent cartridge, resulting in the maintenance of

the desired type of dialysate (Figure 26-4).

Fig. 26-4. The single-use sorbent cartridge is commercially available in a number of different sizes. It consists of several

components, which, from the bottom of the cartridge up, include scavenger (ie, purification), urease, zirconium

phosphate, hydrated zirconium oxide, and activated carbon layers. The scavenger layer consists of activated carbon

and zirconium oxide. This layer removes trace metals such as copper and oxidizing agents such as chloramine, which

would otherwise inactivate the second layer. The second layer consists of urease. This catalyzes the reaction of urea

into ammonia and carbamic acid, which in aqueous solution form ammonium in equilibrium with ammonia, and

bicarbonate. The third layer consists of zirconium phosphate, which serves as a cation exchanger. Thus, the ammonium

ions that result from the urease layer, in addition to calcium, magnesium, and potassium, are exchanged for sodium

and hydrogen ions in a ratio of 8:1 by the zirconium. The fourth layer, of zirconium oxide, serves as an anion exchanger,

in which phosphate is exchanged for acetate. The final layer consists of activated carbon, which adsorbs creatinine, uric

acid, and other organic compounds. The use of this sorbent-based system allows dialysis to be conducted using potable

water, rather than water that would otherwise have to be treated with filters, deionizers, and reverse osmosis

membranes. Reprinted with permission from Organon Teknika Corp. Sorbent Dialysis Primer. Durham, NC: Organon

Teknika Corp; 1988: 3.

Used Dialysate

Nothing Ammonium

(Converts Urea) Carbonate

Binds Releases

• Activated

Carbon Layer

• Hydrous Zirconium

Oxide Layer

• Zirconium

Phosphate Layer

• Urease Layer

• Purification Layer

Creatinine Nothing

Uric Acid

Other Organics

Middle Molecules

Phosphate Acetate

Fluoride

Heavy Metals

Ammonium Sodium

Calcium Hydrogen

Magnesium

Potassium

Other Cations

Heavy Metals Nothing

Oxidants

Chloramines

Cartridge Effluent
Anesthesia and Perioperative Care of the Combat Casualty

734

The major drawback of the sorbent-based system

is that the sorbent cartridge has a finite capacity.

That is, the ability of the cartridge to remove urea is

limited by the ability of the zirconium-phosphate

layer to exchange ammonium, which is derived

from the urease-based catalysis of urea, for sodium

and hydrogen. When this layer is saturated, additional ammonia cannot be processed and can diffuse into the patient. The capacity of the cartridge

to handle urea depends on its size. High-capacity

cartridges can remove 28 g of urea nitrogen (ie, 60 g

or 1,000 mmol of urea). Detection of ammonia is

facilitated by the use of ammonia test strips. When

hypercatabolic patients are dialyzed and excessive

urea must be removed, either the dialysate must be

monitored for ammonia or, more commonly, the

cartridge can simply be replaced with a fresh cartridge halfway through the treatment.

Equipment and Support

The machinery and other technical requirements

for hemodialysis are substantial. Modern machines

are equipped with numerous safety features and

monitoring devices. Because many are based on

solid-state circuitry, a surge-free electrical current

is required. Electrical generators or fixed-facility

power plants must be capable of providing 110- to

120-V, 50-Hz power to support machines that are

manufactured in the United States. These machines

are sufficiently complex that several weeks are required to train operators. Relatively sophisticated

medical maintenance support and spare-part

backup, primarily in the form of spare circuit boards,

are required, as user-based maintenance capabilities are minimal. Supply modules have been configured that contain all the material necessary to

conduct dialysis. The machines contained in a

DEPMEDS module (deployed at the third echelon)

are slightly larger than a large suitcase, and weigh

approximately 50 lb.

Hemodialysis is conducted by dialysis technicians, who are corpsmen who have special training

in dialysis, and who are supervised by nurses

who have undergone similar specialized training.

A 6-month course for dialysis technicians is conducted at Walter Reed Army Medical Center

(WRAMC) in Washington, D. C., and a course has

recently been started for registered nurses who

wish to become dialysis nurses. Technicians and

nurses alike then receive personnel skill identifiers

that facilitate their assignment to facilities where

dialysis will be provided. The standards of practice

required to care for the typical patient with ARF

are that one technician provide treatment to a single

patient. Moreover, a registered nurse with

experience in dialysis should be present in any

location where patients are being dialyzed. Dialysis personnel are also trained in assisting nephrologists in the placement and subsequent care of

catheters for dialysis. Because a typical dialysis

treatment requires nearly 1 hour of preparation, 4

hours for the actual treatment, and nearly 1 hour to

prepare for the next patient, hemodialysis is a labor-intensive process.

Peritoneal Dialysis

Peritoneal dialysis was used during the Vietnam

War for milder forms of ARF. This form of dialysis,

in which the peritoneal membrane serves as the

dialyzing membrane, is inherently much less efficient than hemodialysis. Access to the peritoneal

cavity is achieved via either the percutaneous placement of a stiff peritoneal catheter or, preferably, the

placement of a softer, curled catheter through a small

incision using local anesthesia and direct visualization of the peritoneal cavity. As with hemodialysis,

solutes are removed by a combination of diffusion

and convection. Ultrafiltration is caused by the

movement of water from the blood into the peritoneal cavity in response to the placement of hypertonic

dextrose (1.5%, 2.5%, or 4.25%) into the peritoneal

cavity. Solute and fluid removal rates are substantially slower than those achieved with hemodialysis,

with BUN and creatinine clearances approximating

15 and 5 mL/min under optimum conditions.

Peritoneal dialysis has some advantages over

other forms of dialysis:

• Anticoagulation is not required; thus, patients who are at high risk of bleeding, or in

whom bleeding might be catastrophic, can

receive therapy.

• There is very little hemodynamic stress,

and patients with hypotension who cannot

be hemodialyzed can undergo peritoneal

dialysis successfully.

However, for military medicine, the disadvantages

outweigh the advantages:

• The casualty must have an intact peritoneal

cavity. Only rarely can patients successfully undergo acute peritoneal dialysis after abdominal surgery.

• Peritoneal dialysis also requires large quantities of dextrose-containing fluid; delivery, storage, and maintenance of sterility of

this fluid represent logistical challenges.
Acute Renal Failure

735

Although peritoneal dialysis has been used in patients with posttraumatic ARF,92,93 the disadvantages make it of limited use in posttraumatic renal

failure, and there is no provision for this form of

therapy in our current DEPMEDS planning.

Hemofiltration

Hemofiltration is the newest form of therapy

available and has shown promise in the management of critically ill patients.94,95 This approach to

dialysis utilizes a polysulfone membrane configured in a hollow-fiber geometry. Both hydraulic

conductivity and solute passage are substantially

greater than they are with hemodialysis. Solute

removal occurs through convection, in which transport of the solute depends on the solute’s being

swept along by the moving stream of solvent (ie,

solvent drag) and not on the size of the solute

molecule. As long as the size of the solute does not

exceed the size of the pore in the membrane, the

solute will be cleared with its solvent. However, the

concentration of solute in the blood will not change.

The porosity of the hemofilter membrane is such

that large volumes of fluid can be removed. Ultrafiltration rates of 50 to 60 mL/min are theoretically

achievable; in practice, removal of more than 1 L/h

is commonplace. However, because the concentration of undesired substances in the blood does not

change, other maneuvers must be utilized to effect

a substantial reduction of nitrogenous waste concentration. One such method is to replace fluid

removed by the hemofilter concurrently, usually in

a postfilter mode, with appropriate quantities of

sterile, pyrogen-free, isotonic, electrolyte-balanced

fluid. This method is true hemofiltration, and is

effective in controlling concentrations of nitrogenous waste products in the blood.

Continuous Arteriovenous Hemofiltration

No blood pump is required in continuous arteriovenous hemofiltration (CAVH), as the patient’s

systemic arterial pressure determines the rate of

blood flow through the extracorporeal circuit. Other

determinants of the efficacy of this system include

the type of cannulae used for angioaccess and the

length of tubing utilized for ultrafiltrate collection.

CAVH requires that a large artery and vein be

cannulated or that an external arteriovenous shunt

be surgically placed. The term CAVH should be

reserved for the use of a hemofilter and postfilter

replacement fluid therapy (ie, hemodilution), in

which the goal of therapy is control of nitrogenous

waste and circulatory overload in the oliguric or

anuric patient with ARF. The enormous quantities

of intravenous-quality fluid required to achieve

reductions in concentrations of nitrogenous waste

make this form of therapy logistically problematic

in a wartime setting.

Slow, Continuous Ultrafiltration

Slow, continuous ultrafiltration (SCUF) is identical to CAVH except that no replacement fluid is

administered. Instead, the hydraulic conductivity

of the hemofilter is utilized, along with the patient’s

own blood pressure, to remove an isotonic

ultrafiltrate of plasma. This is very effective therapy

for volume overload. Concentrations of substances

in the blood do not change, and waste removal is

limited to the amount of ultrafiltrate removed. Thus

this therapy is not effective by itself for azotemia.

Conversely, it can be utilized effectively for both

acidemia and hyperkalemia, since excessive fluid

can be removed, allowing space for bicarbonate,

glucose, and insulin. However, because neither

acid nor potassium is actually removed from the

body in substantial quantities by this procedure,

SCUF is probably best considered as a temporizing

measure to be utilized until the patient can be treated

with hemodialysis.

Continuous Arteriovenous Hemodiafiltration

The newest form of therapy available is a hybrid

of CAVH and SCUF, called continuous arteriovenous hemodiafiltration (CAVH-D).96,97 In this

technique, SCUF is performed with the simultaneous infusion of an electrolytically balanced solution countercurrent to the blood path in the

hemofilter apparatus. Such fluid can be pumped

with an intravenous fluid–control device, at a rate

of 1 L/h; peritoneal dialysate is often used as the

fluid. Although the system is relatively inefficient,

the mixture of convective- and diffusion-based transport does remove unwanted solutes from the body.

Bicarbonate or base-precursors, usually acetate or

lactate, diffuse from dialysate into blood, and when

metabolized by the liver to bicarbonate, result in the

attenuation of acidemia. However, since dialysate

flows are approximately 1 L/h, the quantities of fluid

required are similar to those required by true CAVH.

There are several advantages of SCUF, with or

without hemodiafiltration, over hemodialysis in

critically ill patients98,99:

1. Because no blood pumps or dialysis machines are required, the machinery and

personnel requirements for SCUF are sub-
Anesthesia and Perioperative Care of the Combat Casualty

736

stantially less than for hemodialysis. The

cognitive and technical requirements that

are necessary to be able to supervise or

perform SCUF or its variants are readily

taught by nephrologists to registered nurses

with critical care training, and to internists

or intensivists or both.100 Many of the graduate medical education programs in the military provide this form of training to appropriate resident physicians.

2. Compared with hemodialysis, there is very

little hemodynamic instability or hypotension attributable to the extracorporeal

procedure itself. The reasons for this are

not clear but probably relate to the fact that

SCUF does not produce changes in plasma

osmolality as does hemodialysis.

3. The membrane material in hemofilters appears to be more biocompatible than

hemodialysis membranes; thus, allergic

reactions and sequestration of leukocytes

are uncommon.

4. Critically ill patients with ARF have enormous nutrient requirements; it is not uncommon for such patients to need 3 to 5 L of

parenteral nutrition daily. Removal of these

substantial volumes of fluid with conventional hemodialysis is often hindered by refractory hypotension; thus, optimal nutritional support cannot be provided.

5. The use of SCUF does not preclude intermittent hemodialysis. In fact, many patients with ARF who require dialytic support may need virtually continuous volume

control, with only intermittent solute removal. Thus, in my experience at WRAMC

(1980–1985) with 101 patients dialyzed for

ARF, volume overload was by far the most

frequent cause for intervention, while

azotemia, hyperkalemia, and acidemia

were indicated far less frequently.101 Many

patients with oliguric ARF can be treated

successfully with SCUF and only intermittent hemodialysis.

DIALYTIC MANAGEMENT OF ACUTE RENAL FAILURE

• to eliminate or prevent manifestations of

uremia.

Indications for Dialysis

In modern nephrologic practice, there are no

absolute indications for or contraindications to dialysis, so that virtually any casualty who is not in

the expectant triage category may be considered a

candidate for dialysis, even those for whom dialysis

would have been considered contraindicated in

earlier years. The expanded applicability of dialysis is undoubtedly a result of both a better appreciation of the physiological events that accompany

dialysis and more advanced physiological monitoring systems. I have successfully dialyzed patients

with both closed and open head injuries, patients

actively bleeding from gastrointestinal or pulmonary sources, and patients with virtually refractory

hypotension. However, these patients require intensive resources that are exceedingly scarce in

field hospitals, and the decision to utilize them

must be made in the context of the whole theater’s

need for dialysis support.

The usual indications for dialysis include intractable volume overload, refractory metabolic acidemia, uncorrectable hyperkalemia, and substantial

azotemia, usually defined as concentrations of BUN

and creatinine greater than 110 to 120 mg/dL and 7

The decision to provide dialytic therapy to a

critically ill casualty is one that should not be made

lightly, and should be made by a nephrologist in

consultation with the primary physician after the

risks and expected benefits are weighed. At the

very least, the decision to provide dialysis involves

commitment of substantial personnel, supply, and

time. Dialysis should never be offered to casualties

who have been triaged as expectant. As a general

rule, dialysis should be provided as far rearward in

the theater as possible, and should be considered a

support measure to allow the casualty to be evacuated as soon as possible to a site of definitive medical care. Given the nature of the injuries and illnesses that are associated with ARF, even with the

most favorable circumstances and outcomes, survivors of ARF are virtually never fit to return to any

form of duty for 3 to 6 months.

The goals of dialysis are

• to maintain relatively normal electrolyte

concentrations;

• to maintain predialysis BUN concentration

of 80 to 90 mg/dL and creatinine concentration of 6 to 8 mg/dL;

• to maintain an extracellular fluid volume

that permits required fluid administration

and acceptable oxygenation-ventilation

parameters; and
Acute Renal Failure

737

EXHIBIT 26-4

INDICATIONS FOR DIALYSIS OF

PATIENTS WITH ACUTE RENAL FAILURE

Intractable metabolic acidemia

Intractable volume overload

Intractable hyperkalemia (dialysis is the

definitive therapy)

Uremic pericarditis

Uremic encephalopathy

Dialyzable toxin ingestion

Gastrointestinal hemorrhage after localization

Bleeding diathesis prior to surgery

to 9 mg/dL, respectively (Exhibit 26-4). These levels of azotemia may prompt many nephrologists to

institute dialysis even without uremia. Moreover,

overt uremia (manifested by pericarditis, altered

mental status, or bleeding diathesis) signifies that

dialysis should be instituted as soon as possible.

Finally, hypercatabolic ARF, in which the daily

incremental changes in BUN or creatinine or both

exceed 40 mg/dL and 3 mg/dL, respectively, may

occur frequently in wartime and generally requires

dialysis.

Volume Overload

Intractable volume overload in the oliguric patient is the most common indication for dialytic

support, and is manifested by progressive weight

gain, substantial edema, and, more importantly, by

accumulation of fluid in the lungs with progressive

hypoxemia. Accumulation of ascitic fluid may further compromise respiratory function. If possible,

a diagnosis of intravascular volume overload made

on clinical grounds should be corroborated by central venous pressure or hemodynamic monitoring.

Although many patients will exhibit salt and water

accumulation secondary to adult respiratory distress syndrome, hypoalbuminemia, or myocardial

dysfunction, fluid accumulation in these latter circumstances is exceedingly more difficult to remove

with an extracorporeal circuit than is true intravascular volume overload. Injudicious use of SCUF or

hemodialysis may result in profound hypotension

and retard recovery from ARF.

In patients for whom volume removal is intended,

blood pressure can be sustained by a number of

different maneuvers:

• Many patients are already receiving vasoactive drugs when dialytic support must

be provided. Maintenance of a successful

extracorporeal circuit may require that

these agents be continued, often in higher

doses. Dopamine can be used in doses of

up to 10 μg/kg/min; higher doses are not

usually effective.

• If myocardial performance is depressed as

manifested by low cardiac output, then

dobutamine, in doses of 1 to 10 μg/kg/min,

is the preferred agent. In my experience,

there is no added efficacy for the two drugs

together compared with their use alone.

Levophed, administered as an infusion of

4 μg/min, may be required for severe

hypotension, as may be combinations of

isoproterenol, epinephrine, or calcium.

• Correction of metabolic acidemia by infusion of sodium bicarbonate may restore

response to pressor agents. Salt-poor albumin (25%) will often reverse hypotension

on dialysis by mobilizing edema into the

vascular space.102

• Similarly, packed red blood cells can be

administered through the venous line of

the dialysis circuit, particularly if the hematocrit is lower than 0.30. There is little to

be gained by raising the hematocrit past

this point. Higher hematocrit values (a) are

associated with an increased incidence of

membrane clotting and (b) reduce the efficiency of the dialysis procedure by increasing plasma oncotic pressure, which tends

to retard fluid removal from the blood across

the dialysis membrane. However, in general, if the systolic blood pressure cannot be

maintained above 100 mm Hg, dialysis will

not be possible. Even with SCUF circuits, a

mean arterial pressure of at least 60 mm Hg

is required.

Metabolic Acidemia

Refractory metabolic acidemia responds to dialysis because organic acids such as lactic acid are

readily removed by the dialysis membrane. In

addition, the dialysate contains either a base precursor, such as acetate, or a base such as bicarbon-
Anesthesia and Perioperative Care of the Combat Casualty

738

ate, which diffuses into the patient’s blood owing to

a favorable concentration gradient. The usual bicarbonate concentration in such situations can range

from 25 to 35 mmol/L. Finally, even with SCUF

alone, the removal of extracellular fluid will provide space for sodium bicarbonate to be infused

into the patient.

Hyperkalemia

Uncorrectable hyperkalemia also favorably responds to dialysis. The removal of potassium is

extremely rapid, and overt cardiac toxicity can often be attenuated within the first hour of dialysis.

The concentration of potassium in the dialysate

should be prescribed for the individual patient.

Extremely low potassium dialysate concentrations,

such as 0 or 1 mmol/L, should be used only with

extreme caution, because rapid shifts of potassium

from the blood to the dialysate may be associated

with cardiac arrhythmias. It is often more prudent

to begin with a 3- to 4-mmol potassium bath and to

lower the concentration periodically during the

treatment. Although SCUF removes only limited

amounts of potassium from the body, removal of

extracellular fluid will provide space for the administration of calcium, glucose and insulin, or bicarbonate as necessary.

Uremia

Azotemia is a sign: elevated concentrations of

nitrogenous waste products in the blood. Uremia,

however, is a syndrome. Thus, patients can be

azotemic but not uremic. The detection of severe

uremia in critically ill patients can be exceedingly

difficult. Classically, uremia is described as a constellation of abnormalities thought to be due to

retention of toxins that have not been precisely

defined. Elevated concentrations of BUN and creatinine, while considered markers of toxin retention,

may not be toxic themselves, as there is not a linear

relation between their concentration and the severity of symptoms. Pericarditis, nervous system abnormalities, and bleeding are the typical major clinical features of severe uremia. In general, the medical

officer should not attribute any of these disorders to

uremia unless the BUN and creatinine concentrations exceed 100 to 120 mg/dL and 6 to 9 mg/dL,

respectively. Critically ill patients with ARF will

often have coexistent liver, cardiac, hematological,

or central nervous system dysfunction from either

their primary illness or the effects of drugs or anesthetics. The contribution that renal failure makes in

such generalized physiological dysfunction is often

hard to determine.

Uremic Pericarditis. Uremic pericarditis may

only be manifested by a three-component friction

rub, which can be evanescent and extremely difficult to detect in a patient maintained on a ventilator.

The electrocardiographic changes that accompany

uremic pericarditis are sufficiently nonspecific as to

be unhelpful. In the absence of chest pain, this

complication of ARF can be extremely difficult to

detect, although it may occur in as many as 15% of

patients. Although an echocardiogram can readily

detect a pericardial effusion, many patients have

pericarditis without effusion. Moreover, echocardiograms will not be available in the combat theater. Thus, increasing size of the cardiac silhouette

on chest radiograph or progressive hypotension,

particularly if the patient is on dialysis, may be the

only clues to the presence of uremic pericarditis.

The treatment for pericarditis in this setting is the

institution or intensification of hemodialysis.103

Generally, patients will respond quickly to the

former. The development of pericarditis in a patient already receiving dialysis for ARF is of concern, and should lead to a search for pericardial

infection.

Neurological Abnormalities. The neurological

abnormalities seen in ARF are quite diverse and

include abnormalities of both central and peripheral nervous system function. Alterations in mental

status range from minor abnormalities in sophisticated cortical function to profound coma. The latter

is virtually never seen in patients with ARF unless

there is a contributing cause besides renal failure.

Neuromuscular irritability, manifested by hyperreflexia and clonus, can be seen with severe

azotemia. Neurological abnormalities respond only

variably to dialysis, because they are seldom caused

by renal failure alone. Furthermore, peripheral

neuropathies and clonus may be masked by the

neuromuscular paralytic agents that are often used

in ventilated patients.

Bleeding Disorders. Bleeding disorders occur

frequently in patients with ARF. It is been my

practice to attempt to determine the precise cause of

bleeding rather than to attribute it a priori to uremia.

These patients may bleed from any of the disorders

that cause bleeding in critically ill patients without

ARF. For example, gastrointestinal hemorrhage

may be due to stress ulcers or ischemic areas of

bowel. There may be deficiencies or inhibitors of

coagulation factors. Because dialysis generally re-
Acute Renal Failure

739

quires anticoagulation, it is appropriate to eliminate those causes of bleeding that are not due to

renal failure before instituting dialysis. Moreover,

if hemodialysis is not available or if the patient

must undergo surgery before it can be arranged,

nondialytic measures can be attempted. One of the

most effective is the infusion of desmopressin acetate, a vasopressin derivative, which is administered at a dose of 0.3 μg/kg in 50 mL of 5% dextrose

in water 4 to 6 hours prior to surgery or other

intervention. This therapy is more effective than

the infusion of fresh frozen plasma and can be

repeated several times in a 2- to 3-day period.104

It has been known for years that uremia is associated with inhibition of platelet function, so that

despite adequate numbers, platelets do not function properly.105 Bleeding due to uremia is usually

diffuse and is manifested by oozing from the gastrointestinal tract as well as from venipuncture sites.

Bleeding may also involve serous surfaces such as

the pleural and pericardial membranes. Uremic

bleeding generally improves with the institution of

hemodialysis, although it seldom responds to just

one treatment. When hemodialysis is instituted for

bleeding, the activated clotting time should be followed carefully, as these patients may require little

heparin. Moreover, hypotension during dialysis

should be avoided, as it is difficult to determine

quickly at the bedside whether it is due to fluid

removal or bleeding into the pericardial sac with

acute pericardial tamponade, and the hemodialysis

treatment may have to be aborted.

Hypercatabolism

Hypercatabolic ARF is the most dramatic form of

ARF likely to be encountered after trauma, and is

manifested by the rapid development of severe

azotemia and concomitant fluid and electrolyte and

acid–base disturbances.106 Rhabdomyolytic-induced

ARF commonly results in this syndrome. Casualties with multiple injuries will also occasionally

exhibit this picture. Early recognition of the

hypercatabolic nature of a patient’s ARF is important, as dialytic support, in conjunction with nutrition, is vital if the patient is to have an opportunity

to recover. Dialysis is generally begun earlier in

this form of ARF than in other forms, as intensive,

often daily dialysis is usually required to control

metabolic abnormalities. Peritoneal dialysis is ineffective, and SCUF and CAVH are best considered

temporizing measures until conventional hemodialysis can be instituted.

Complications of Dialysis

Although the decision to dialyze is made by the

nephrologist after the risks and benefits of such

therapy are considered, the actual treatment itself is

conducted by either a dialysis technician or a nurse.

Hemodialysis is associated with a number of potential complications that mandate that it be conducted

by trained personnel (Exhibit 26-5).107 The most

common complication is hypotension, which may

be seen at any time from the initiation of the treatment until its conclusion. Its management has been

previously discussed. Maneuvers to be utilized by

dialysis personnel in response to hypotension are

outlined by the nephrologist at the onset of each

treatment. All agents administered during hemodialysis should be infused into the blood lines distal

to the artificial kidney so as to prevent rapid clearance of the drug or clotting of the membrane. Over

the first hour of dialysis, the blood flow should

gradually be increased from 100 to 125 mL/min to

200 to 250 mL/min. Acutely ill patients may not

tolerate higher blood flows; such flows are unnecessary, as very effective dialysis is achieved with

blood flows of 250 mL/min.

Other complications are related more to the technical aspects of hemodialysis.108 These include

hemolysis from (a) trace metal contamination of the

water used for dialysate or (b) excessive dialysate

temperature. With either situation, the blood in the

blood lines becomes a translucent, cranberry red.

The procedure must be stopped instantly and the

entire extracorporeal circuit discarded. Abnormalities in the electrolyte composition of the dialysate

EXHIBIT 26-5

ACUTE COMPLICATIONS OF

HEMODIALYSIS

Hypotension

Disequilibrium syndrome

Hemorrhage

Arrhythmias

Pulmonary dysfunction

Technical errors: dialysate composition, water/

air embolism, kidney rupture
Anesthesia and Perioperative Care of the Combat Casualty

740

may result in progressive hyponatremia or

hypernatremia: either situation will result in progressive deterioration in the patient’s mental status. If a sorbent-based system is used, the dialysis

technician should be instructed to conduct dialysis

with dialysate composed of bicarbonate as the base,

with a sodium concentration of 128 to 130 mmol/L.

The dialysate sodium concentration will rise as

dialysis proceeds, since the reaction of urea with the

zirconium phosphate layer of the sorbent cartridge

will liberate sodium into the bath. Dialysate electrolyte composition is monitored on-line with a

conductivity meter, however, and malfunction is

uncommon. Occasionally, an artificial kidney will

have a defective seal and will rupture during the

treatment. The blood pump must be stopped instantly and the lines clamped to prevent the patient’s

exsanguination. Finally, air may enter the circuit

from a defective blood line or if the technician uses

an “air rinse” to clear the lines at the conclusion of

the treatment. Air will be trapped in the patient’s

right atrium and ventricle, and may result in cardiac collapse. The treatment involves placing the

patient on the left side so that the air rises to the top

of the cardiac chamber. Small quantities will gradually be reabsorbed, but larger quantities may have

to be aspirated by a percutaneously placed intracardiac catheter.

Practical Aspects of Dialysis

Monitoring of the patient during the dialysis

procedure is extremely important and is the responsibility of dialysis personnel. Vital signs should be

recorded every 15 minutes. Bed scales will not be

available in the theater; therefore, the blood pressure and pulse are useful indicators of the patient’s

ability to tolerate removal of extracellular fluid.

Often, overt hypotension will be preceded by an

increase in the pulse rate, and should be avoided to

prevent ischemia from damaging other organs and

further injuring the kidneys. In general, critically ill

patients should undergo hemodialysis while on a

cardiac monitor, and should receive supplemental

oxygen to attenuate the almost universal fall in

oxygen tension seen with the treatment. No other

treatments, including wound care, should be performed during hemodialysis.

Conversely, SCUF or CAVH-D are prescribed

and initiated by nephrologists and dialysis personnel but are conducted by intensive care unit personnel. The nephrologist and dialysis personnel should

obtain angioaccess, set the operating parameters of

the system, and ensure that the system is operating

correctly. Operating parameters to be established

include

• the level of anticoagulation that is desired,

• the dosage of heparin that is required to

maintain this level,

• limits of ultrafiltration rates that are acceptable, and

• the types and frequency of monitoring techniques that are to be used.

Intensive care personnel should ensure that nurse

providers receive in-service training from dialysis

personnel, who should remain available for consultation and assistance. However, one of the principal reasons for choosing SCUF or CAVH-D over

hemodialysis is that there are relatively few dialysis-trained personnel in the theater. Widespread

availability of SCUF and CAVH-D permit dialytic

therapy of ARF to be made available to more casualties than could be managed by dialysis personnel

alone.

SCUF and CAVH-D are remarkably free of complications, given the severity of illness in the patients to whom these therapies have been applied.109

Hypotension due to either procedure is uncommon,

since the patient’s mean arterial pressure is the

driving force for ultrafiltration. Should hypotension

occur, ultrafiltration will slow down or stop entirely. However, a diminution in the ultrafiltration

rate is also a signal that the filter may be clogging

with blood clots. If filtration begins to slow, nursing personnel should check both the activated clotting time, to ensure that it is within the prescribed

range, and the patient’s blood pressure. The only

other significant complication of either treatment is

bleeding from the catheter sites. This is extremely

common in the first few hours after their placement,

but will generally respond to a pressure dressing

applied for a few hours.

The desired ultrafiltration rate is established by

the needs of the patient. In general, most patients

will require several hundred milliliters of fluid removal per hour to permit nutrition and antibiotic

administration, in addition to removal of the excessive salt and water that have accumulated during

the days prior to initiation of the procedure. Fluid

removal across a hemofilter is governed by the

same Starling forces that govern fluid removal across

a capillary. Thus, the forces tending to result in

fluid removal include the mean arterial pressure,

which is dependent on the blood flow, and the
Acute Renal Failure

741

pressure exerted by the column of fluid in the collection tube. Blood flows in a typical patient

may range from 60 to 100 mL/min, depending

on the type of angioaccess and the size of the

cannulated artery. The pressure exerted by the

column of fluid in the collection tube depends on

the length of the tube. Excessive ultrafiltration can

be slowed by shortening this tube. The principal

force that retards fluid removal is the oncotic pressure of the blood, which is predicated on the hematocrit and the protein concentration in the blood.

Hematocrits greater than 0.30 and plasma protein

concentrations greater than 6 to 7 mg/dL are associated with low ultrafiltration rates. The net ultrafiltration rate is a balance between these forces. A

convenient method of determining whether ultrafiltration is too excessive is to check the hematocrit

at both the arterial and the venous sides of the

hemofilter. The arteriovenous difference should

not exceed 10% to 15%.

If CAVH-D is being performed, we should remember that a liter of dialysate will be collected

each hour, in addition to the volume of ultrafiltrate.

Total ultrafiltrate should be measured each hour;

this is greatly facilitated by placing a large-capacity

collection bag on a small scale so that weight changes

can be monitored, rather than volume changes manually measured, each period.

Because SCUF results in an isotonic ultrafiltrate

of plasma, the biochemical composition of plasma

can be checked simply by sampling the ultrafiltrate

periodically. This minimizes the need for peripheral venipunctures in fully anticoagulated patients.

However, because CAVH-D results in some diffusive transport, this method is not valid in patients

undergoing this form of therapy.

Timing and Frequency of Dialysis

Hemodialysis is an intermittent procedure that

requires 3 to 4 hours. It may be required daily in

some patients, while two to three treatments per

week may suffice in others. With the four goals of

dialysis in mind—to maintain relatively normal

electrolyte concentrations; predialysis BUN concentration of 80 to 90 mg/dL and creatinine concentration of 6 to 8 mg/dL; extracellular fluid volume

that permits required fluid administration and acceptable oxygenation–ventilation parameters; and

to eliminate or prevent manifestations of uremia—

the decision to dialyze is made anew each day. This

decision is made far easier when the patient’s biochemical values, weight, and accurate flow sheets

are available for the nephrologist on a timely basis.

Because dialysis is as scarce a resource as is, for

example, the operating room, close coordination

between intensivists, surgeons, and nephrologists

will permit the patient to receive optimum care.

PROGNOSIS AND OUTCOME OF ACUTE RENAL FAILURE

Most nephrologists feel that dialysis does add substantially to the care of patients with ARF, and that

our inability to effectively treat infections and the

complications of nonrenal organ failure are the principal reasons why the mortality of ARF has remained so high. To provide insight into better ways

to treat patients with ARF, I will review some of the

extensive experience that has been gained over 4

decades of treatment of ARF. Several studies examined are probably of more historical than practical

interest, as they reflect experience of the decades of

the 1960s through the 1980s. General improvements in medical intensive care since the mid-1980s

have made analysis of older experiences very problematic in terms of applying their conclusions to

current patient populations. Recent studies, which

incorporate techniques and practices still in use,

may provide more useful information.

In 1960, P. E. Teschan and his colleagues110 reported their experience with prophylactic hemodialysis in the treatment of 15 patients with ARF at

The mortality of ARF has remained relatively

constant since the introduction of dialysis during

the Korean War. This fact can be interpreted in

different ways:

• Regarding posttraumatic ARF, it is possible that we now provide dialysis to patients who, because of better resuscitation

procedures than in the past, might previously have died of shock without ever developing the need for dialysis.

• Regarding patients who develop ARF in

the context of nephrotoxic injury or surgery, it is possible that these patients

are older and have more associated

comorbidity than patients previously offered dialysis.

• Alternatively, dialysis may not contribute

to the overall management of patients with

ARF, and may represent an expensive, albeit ineffective, technology.
Anesthesia and Perioperative Care of the Combat Casualty

742

the Institute of Surgical Research at Brooke Army

Medical Center, San Antonio, Texas. Teschan postulated that the uremic syndrome represented a

generalized toxic state in which harmful, albeit

dialyzable, substances resulted in cumulative injury of many tissues, leading to sepsis and other

complications that would result in death. He reasoned that prophylactic dialysis would remove these

toxins and prevent both uremia and its lethal

sequelae. He dialyzed patients when their BUN

concentrations approached 120 mg/dL, and reported a marked attenuation of uremia, as manifested by improved mental status, appetite, and

reduced bleeding. Moreover, he noted an improvement in the resistance to infection and a reduction

in the severity of infection.

Teschan’s results extended those of R. C. Swann

and J. P. Merrill,13 who in 1953 reported their extensive experience with dialysis of patients with ARF

in Boston, Massachusetts. These two reports, in

conjunction with reports of the results of dialysis

being performed in U.S. military hospitals in Korea,

led to the widespread application of dialysis for the

treatment of ARF. However, the reports of subsequent experience failed to demonstrate a convincing effect of dialysis on the overall mortality of ARF.

In 1973, A. C. Kennedy and colleagues111 analyzed their experience with 251 patients with ARF

treated between 1959 and 1970, including 133 patients (53.8%) with ARF in the surgical setting. Of

this group, 32 (24%) sustained ARF from multiple

injuries, while the remainder developed ARF after

surgical procedures, generally of the abdomen. The

mortality in the trauma group was 50%, while the

overall mortality in the group was 58%. One hundred twenty-four of the patients underwent dialysis, including all but one of the patients who sustained multiple trauma. The investigators

determined that nearly two thirds of the deaths,

particularly in the group sustaining trauma, were

due to the effects of the trauma itself. Complications including pneumonia, gastrointestinal hemorrhage, cardiac failure, and sepsis played a role in

at least 30% of the deaths. Moreover, when analyzed separately, the investigators believed that

sepsis was directly responsible for 40% of all deaths.

In 1972, R. B. Stott and his colleagues112 reported

their experience from 1969 to 1971 with 109 patients

with established ARF. While the overall mortality

of the group was 57%, the investigators stratified

their patients into two ARF groups: medical and

surgical-traumatic. The latter group, consisting of

55 patients, experienced a 65% mortality. In patients who had proven sepsis, the mortality was

72%; patients in whom sepsis was not suspected

had a mortality of 47%.

In 1978, McMurray and colleagues113 reported

their experience with 276 patients with ARF from

1967 to 1975, of whom 240 required dialysis. There

were 117 surgical patients and 49 trauma patients,

in whom the mortality was 44% and 35%, respectively. These investigators stratified their patients

for complications, and found that survivors experienced a mean of 2.2 complications, while nonsurvivors experienced a mean of 3.8 complications (P <

.001). In contrast to many studies, these investigators were also able to demonstrate an adverse impact of age: older patients fared significantly worse

than younger patients. The impact of advancing

age has long been considered a powerful predictor

variable, although this has not been demonstrated

in all studies.

G. S. Routh and colleagues114 conducted an analysis of 114 patients who were dialyzed for ARF

between 1969 and 1978. In their study, published in

1980, the patients were divided into two groups: 58

patients, primarily with multiple organ failure, who

were treated in an intensive care unit, and 56 less

severely ill patients, who were treated in a renal

intensive care unit. The mortality in the former

group was 64%; in the latter group, 37%. These

investigators also demonstrated the adverse impact

of comorbidity and documented that sepsis was the

most common cause of death. Of interest is the fact

that ARF itself was believed to be the cause of death

in only two patients.

In 1972, D. Kleinknecht and colleagues115 provided a convincing argument for the aggressive use

of dialysis in ARF with a study that compared

outcomes in two groups of patients treated with

different degrees of dialytic support. These investigators analyzed 500 patients with ARF seen between 1966 and 1970. The patients were divided

into two groups of 279 and 221 patients. Patients in

Group I, who would serve as historical controls,

were dialyzed only when their BUN concentration

exceeded 350 mg/dL; patients in Group II underwent early and frequent dialysis to maintain BUN

concentrations less than 200 mg/dL, and, for the

most part, they received nutritional support. Dialysis exerted a salutary effect on two important parameters: (1) the frequency of gastrointestinal hemorrhage was reduced from 26% in Group I to 18% in

Group II (P < .20), as was the mortality from such

hemorrhage (55% vs 27%, P < .01). And (2), although the frequency of sepsis was not altered, the

mortality from sepsis decreased from 24% in Group

I to 12% in Group II (P < .02).
Acute Renal Failure

743

The results of J. D. Conger’s12 experience with

intensive hemodialysis in the Vietnam War, published in 1975, were discussed earlier in this chapter; in conjunction with the experience of the investigators cited above, Conger’s results were partly

responsible for providing an intellectual basis for a

change in the way patients with ARF were routinely

managed after the early 1970s. From then on it

would be usual for patients with substantial ARF to

receive dialytic and nutritional support prior to the

onset of overt uremia and severe biochemical abnormalities. Notwithstanding the lack of properly

designed, prospective, controlled studies comparing patients treated with and without dialysis, studies published during the 1980s on the outcome of

ARF reflect this aggressive approach to dialysis,

and have largely concentrated on identifying risk

factors that affect prognosis. Thus, several studies

were published in the 1980s on the outcome of ARF.

These studies are important because they reflect the

practices that will likely be employed in treating

future combat-casualty-associated ARF. These practices include the aggressive use of dialysis, combined with intensive nutritional support, general

intensive care management, and powerful antibiotics. The current approach of most nephrologists is

based on the concepts of Teschan110 and Champion106 and incorporates an aggressive, multidisciplinary approach to patients with posttraumatic ARF.

J. Lien and V. Chan116 conducted a retrospective

analysis of 84 patients with ARF treated by

hemodialysis between 1980 and 1984. In their study,

published in 1985, the overall mortality was 63.7%.

These investigators identified several risk factors

that were different between survivors and nonsurvivors, including malnutrition, jaundice,

hypotension, the need for assisted ventilation, heart

failure, and sepsis.

In 1988, J. W. Lohr, M. J. McFarlane, and J. J.

Grantham117 reported on 126 patients who received

dialysis for ARF between 1979 and 1985. Dialysis

was routinely employed for BUN and creatinine

concentrations greater than 100 and 10 mg/dL, respectively. The overall mortality was 75%, and was

dependent on five variables that adversely affected

survival: hypotension, assisted ventilation, congestive heart failure, proven or suspected sepsis, and

gastrointestinal dysfunction. Moreover, these investigators quantified these covariables and demonstrated an inverse relation between survival and

the number of covariables. If no factors were present,

the survival was 62%, while if four or more factors

were present, the survival was only 2.7%.

Also in 1989, F. Liano, F. A. Garcia-Martin, and A.

Gallego118 published the results of a prospective

analysis of their experience with ARF (1979–1985),

during which period they studied a cohort of 228

patients, of whom 87 were treated with hemodialysis. These investigators found that coma, hypotension, and the requirement for assisted ventilation adversely affected survival, which was only

44%. None of the patients died of ARF directly.

Finally, in 1986, D. M. Gillum and colleagues,119

one of whom was J. D. Conger, extended Conger’s

previous observations on the use of dialysis in ARF

by conducting a prospective, controlled study of

intensive dialysis in ARF. Thirty-four patients with

ARF were matched for etiology and a number of

clinical characteristics, including nutrition and other

support, and were divided into two groups: the first

group received intensive dialysis to maintain BUN

and creatinine concentrations less than 60 and 5

mg/dL, respectively; the second group was more

routinely dialyzed and maintained BUN and creatinine concentrations less than 100 and 9 mg/dL,

respectively. There were no significant differences

in complication rates or in mortality, which was

59% in the intensive group and 47% in the

nonintensive group. This study has been criticized

for its small sample size, however, by proponents of

dialysis. Interestingly, some investigators120 questioned whether hemodialysis, because of its hemodynamic stress, delays the recovery from acute renal failure.

The experience at WRAMC has been similar. We

analyzed our experience with 101 patients dialyzed

for ARF at WRAMC during the period 1980 through

1985 and published the results in 1985.101 The overall mortality was 64%, and infection was directly

responsible for nearly half the deaths. Our experience since then has corroborated that previous experience. Patients rarely die of pericarditis, gastrointestinal hemorrhage, or other features of uremia

itself. They die of infection. The lungs and intraabdominal viscera are the presumed sites of the

majority of these infections, based on the types of

organisms recovered from blood cultures. We rarely

see lethal infections from the urinary tract or

indwelling catheters. Instead, the principal organisms are Gram-negative organisms, which are resistant to many antibiotics, and fungi. These infections are notoriously difficult to treat and are often

unresponsive to all forms of antibiotics and antifungal agents. Although there are exceptions, in general, patients who develop ARF and require dialysis

either recover in the first 10 to 14 days after the renal

failure ensues, or they only rarely recover.121
Anesthesia and Perioperative Care of the Combat Casualty

744

The studies described above have been conducted

with the goal of identifying factors that affect prognosis, and have largely been based on cohorts in

which dialysis was provided. Despite differences

in study design, patient populations, and treatment

protocols, the findings are consistent.122 Risk factors, which appear as covariables in statistical analyses, can be identified that exert a predictable effect

on outcome, and the more risk factors that are

present, the worse the outcome. Dialysis has not

measurably reduced the substantial mortality associated with ARF.

The whole problem of the mortality of ARF and

the impact of dialysis on its outcome has been

reviewed.2,123,124 Not surprisingly, the vast majority

of the available literature implicates the devastating effects of multiple organ failure and infection on

mortality. Little evidence exists to suggest that

improvements in the quality or quantity of dialysis

would have any impact on outcome. J. S. Cameron123

summarized the data from a number of different

studies, in which the effects of organ failure and

sepsis were analyzed for their contribution to mortality. In the aggregate, these data suggest that an

identifiable cohort of patients who develop ARF

may be doomed despite our best efforts. Predictive

functions utilizing clinical variables can predict

outcome correctly in 70% to 80% of patients.49,125

Nonetheless, no predictive equation predicts outcome infallibly, and the datasets on which such

equations are based have included patients with

substantial comorbidity and advanced age compared with the young, previously healthy soldiers

who will develop ARF in wartime. It is possible that

casualties in future conflicts who develop ARF will

provide the best evidence for the salutary effects of

aggressive dialytic and general intensive care support.

SUMMARY

Casualties with ARF are both a medical and a

logistical problem for military medical personnel.

The condition was first recognized during World

War II and has been associated with a persistently

high mortality in subsequent conflicts, despite improvements in the evacuation and treatment of casualties with ARF in the theater.

ARF usually results from either ischemic or

nephrotoxic injury; commonly, both forms of injury

exist in a given casualty. Multiple theories have

been advanced regarding the pathophysiology of

ARF. None are completely satisfactory, and knowledge of cellular and molecular biology has increased

our understanding of this disorder. Both renal

ischemia and nephrotoxic injury result in structural

and functional abnormalities of the renal epithelium that subserve clinical injury. A number of

promising therapeutic maneuvers, many based on a

more in-depth understanding of the disorder, are

presently in clinical trials and may soon be available for use.

The approach to the patient with suspected ARF

involves ensuring adequacy of the volume of the

extracellular fluid, patency of the urinary tract, and

elimination of all factors that could potentially damage the kidneys. The determination as to whether

oliguria results from prerenal, postrenal, or intrinsic renal causes is critical. The diagnosis of ARF can

usually be made from the history, physical examination, microscopical and chemical analyses of the

urine, and simple radiographic tests. Patients with

oliguria should be challenged with graded doses of

diuretics, after the extracellular fluid volume has

been restored, to promote urinary flow. Patients

who do not have oliguria are easier to manage in

terms of fluid balance, nutrition, and dialysis requirements. Nutritional support is an important

aspect of the care of the patient with ARF, who

requires a relatively large amount of energy delivered in a small volume of fluid.

The therapeutic options available for casualties

with established ARF include conservative management and dialysis. A number of different types

of dialysis care are available, including conventional hemodialysis and peritoneal dialysis. With

newer, more biocompatible membranes, hemofiltration, ultrafiltration, or a combination of

these treatments can be used. The indications for

hemodialysis include intractable metabolic and

circulatory volume abnormalities. Absolute

contraindications include refractory hypotension and having been triaged as expectant. Despite

the widespread availability of dialysis, the mortality of combat- and trauma-associated ARF remains high. The most common cause of death is

infection, usually associated with multiple organ

failure.

The casualty with ARF is a formidable medical

and logistical challenge. Despite advancements in

our knowledge of renal disease, the mortality of

ARF remains high. We can expect improvement in

the outcome of this disorder when we have better

ways to prevent and treat infection and multiple

organ failure.
Acute Renal Failure

745

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751

Military Medical Evacuation

Chapter 27

MILITARY MEDICAL EVACUATION

COLIN A. B. MCLAREN, QHP, MB, CHB, FC ANAES*; LOUIS M.GUZZI, M.D.†; AND RONALD F. BELLAMY, M.D.‡

INTRODUCTION

HISTORY

LOGISTICAL AND OPERATIONAL ASPECTS

Unit and Division Levels

Corps and Communications Zones: Zone of the Interior

Domestic Aeromedical Evacuation System

MEDICAL IMPLICATIONS OF BIOPHYSICAL EFFECTS OF AEROMEDICAL

EVACUATION

Barometric Pressure

Oxygenation

Gravitational and Accelerative Forces

Thermal Stress

Noise and Vibration

Fatigue and Sleep Lag

MEDICAL DETERMINANTS OF SAFE EVACUATION

In-Flight Medical Problems of Long-Range Aeromedical Evacuation

Patient Conditions Leading to Medical Instability

Preparation for Evacuation

SUMMARY

*Formerly,Air Commodore, Consultant Adviser Anaesthetics, The Royal Air Force (ret); Central Medical Establishment, Kelvin House,

Cleveland Street, London, W1P 5FB, England; Currently, Consultant Anaesthetist, 12 Broadacres, Broad Town, Wootton Bassett, Wiltshire,

SN4 7RP, England

†Major, Medical Corps, U.S. Army; Chief, Combat Trauma Research, Walter Reed Army Institute of Research, Washington, D. C. 20307-5100

‡Colonel, Medical Corps, U.S. Army; Managing Editor and Officer in Charge, Textbook of Military Medicine, Borden Institute, Walter Reed

Army Medical Center, Washington, D. C. 20307-5001
Anesthesia and Perioperative Care of the Combat Casualty

752

INTRODUCTION

Unless an army is prepared to deploy its major

medical assets, including its hospitals, into the

middle of a battlefield, it must be capable of carrying out that “undeniable but unavoidable evil of

evacuation of the sick and wounded,”1 in the words

of Nikolai I. Pirogov, one of the founders of 19th

century military surgery. Pirogov’s use of the word

“evil” may seem extreme, but harmful effects can

arise during evacuation, especially when it is viewed

simply as transportation.

That military medical evacuation is more than

transportation is clear from its official definition.

According to U.S. Army Field Manual (FM) 8-10-6,

Medical Evacuation in a Theater of Operations, military

medical evacuation includes2(p4-1):

• collecting the wounded,

• performing triage,

• providing an evacuation mode or transportation,

• providing medical care en route, and

• anticipating complications and being ready

to perform emergency medical interventions.

Evacuation is not an end in itself but, at a minimum, is a tool that makes possible more effective

treatment. At the same time, by allowing the deployment of the most logistically demanding, immobile, and vulnerable medical assets far to the

rear, evacuation simplifies the commander’s combat service support mission. Ideally, treatment is

ongoing during evacuation.

Implicit in the official definition of medical evacuation is the fact that the act of evacuating casualties

covers a wide spectrum of contingencies that range

from

• manual evacuation (by two-man carry) of

the casualty to a sheltered site 100 m distant, to

• ground ambulance evacuation to a battalion aid station several kilometers distant, to

• helicopter evacuation to a mobile army surgical hospital (MASH) 30 km distant, to

• intratheater (ie, tactical) aeromedical evacuation by fixed-wing aircraft to a communication zone hospital 300 km distant, to

• intertheater (ie, strategic) aeromedical

evacuation by long-range transport to a

hospital in the zone of the interior 10,000

km distant.

Not surprisingly, the indications for evacuation,

the medical diagnoses of the evacuees, and the

differing technical characteristics of the means of

evacuation interact to produce a variety of potential

medical treatment problems. However, certain basic medical truths predicated on human anatomy

and physiology remain constant and cannot be ignored without dire consequences for the casualty.

The potential medical “evil” of evacuation, especially that which may arise from the physiological

threat of aeromedical evacuation, is the primary

subject of this chapter.

HISTORY

Most ancient armies had medical staffs to look

after their sick and wounded, but it would seem

that their chief responsibility was to attend to the

well-being of officers and princes.3 The problems of

removing the sick and wounded from the battlefield were probably not viewed as one of the functions of the medical staff but rather as a logistical

problem that needed to be solved: the dead and

dying on the battlefield interfered with the fighting.

Such considerations no doubt motivated the first

well-documented instance of evacuation, namely,

when Scipio temporarily broke off his ultimately

successful attack on Hannibal in the climactic battle

of the Second Punic War at Zama in 202 BC:

The space between the two corps which still remained on the field was by now covered with

blood, corpses, and wounded men, and the physical obstacle created by the enemy’s rout presented

a difficult problem to the Roman general. Everything combined to make it hard for him to advance

without losing formation: the ground slippery with

gore, the corpses lying in blood-drenched heaps,

and the spaces between encumbered with arms

that had been thrown away at random. However,

Scipio first arranged for his wounded to be carried

to the rear....4(p477)

It is unclear when the rationale for evacuation

was first looked on as medical rather than as the
753

Military Medical Evacuation

logistical process of “clearing the battlefield.” Certainly by the Napoleonic era, some military surgeons recognized that early evacuation from the

battlefield even before the fighting had ended was

a necessary prerequisite for effective treatment.

Foremost among them was Dominique-Jean Larrey,

who was surgeon to Napoleon’s Imperial Guard.

Larrey’s recognition of the need to improve evacuation preceded any of Napoleon’s battles, and he

presented his conclusions regarding evacuation at a

conference held on 17 November 1789. This conference was convened in Paris by the National Convention of the Revolution to study Larrey’s report

describing the medical treatment of French troops

fighting in the battles of Limbourg and Speyer.5 At

this time, the treatment, or lack of it, depended on

the result of the battle: success meant that the casualty would receive some sort of treatment, albeit 48

hours after wounding, whereas defeat meant no

care and almost certain death.

Larrey pursued his ideas despite his initial lack

of success. He developed the use of horse-drawn

vehicles to evacuate the sick and wounded from the

battlefield via the ambulance volante (ie, flying ambulance), which was first used in 1797 on the battlefield of Konigstein, in the Taunus mountains of the

Rhineland Palatinate. Although Larrey’s flying

ambulances were available in only a tiny part of

Napoleon’s army, their ability to provide rapid and

humane evacuation was widely recognized. James

McGrigor, Wellington’s outstanding chief medical

officer in the Peninsular campaign, in attempting to

justify the acquisition of similar vehicles, wrote the

following classic description of evacuation gone

wrong:

The suffering of the sick and wounded was very

great.... They suffered so much by the transport [ie,

slow, clumsy ox-carts—RFB], the weather, and the

privation...that...many of the wounded and those

ill of dysentery arrived in so bad a state as only to

survive a few days....6(p121)

Other modes of transportation were adopted for

the evacuation of casualties during the 19th century. Florence Nightingale was instrumental in

organizing hospital ships to evacuate the sick and

wounded during the Crimean War. (The first reports of the use of ships for the transfer of the

wounded had occurred during the Eighth Crusade,

when galleys were used to move them to Damietta.3

)

At the same time, the rapid growth of railways as

the principal mode of transportation offered an

alternative. Given the appalling state of the roads in

any battle area and the congestion of vehicles traveling to the battle area (causing delays with the

ambulances traveling in the opposite direction),

and the ever-increasing size and complexity of the

rail networks, it is not surprising that several countries investigated the possibility of using the railway systems to permit rapid evacuation of large

numbers of sick and wounded in warmth, light, and

relative comfort, where they could continue receiving medical and nursing care.

The first examples of medical evacuation by rail

occurred in 1859, during the Italian War, when

large numbers of French casualties were moved via

railway. The seriously wounded were transported

in baggage cars, the less seriously wounded in passenger cars.3 During the American Civil War, many

attempts were made to organize a satisfactory evacuation service using railway trains. After many experiments, the Union Army developed a well-organized ambulance train service, which, as well as

carrying the sick and wounded, had facilities to

maintain treatment and provide catering during the

journey. In some of the campaigns, the distance

from the front line to the base hospitals was several

hundred miles. In 1864, the Army of the Cumberland River made use of three trains per day to

transfer the sick and wounded back to Louisville,

Kentucky. The Confederate forces were not so

lucky: only irregular service was available, with

none of the amenities available to the Union forces.3

Owing to the leadership of Jonathan Letterman,

the chief medical officer of the Army of the Potomac,

by the end of the American Civil War military

medical evacuation was seen as a systematic process to be carried out by a dedicated corps of specialists under the command and control of the medical department. Letterman’s influence was such

that he was able to get the U.S. Congress to enact a

law codifying the organization and function of

ambulance corps and ambulance trains.7 Many of

the subsequent developments in military medical

evacuation revolved around the technical characteristics of the evacuation vehicles, but the correctness of Letterman’s doctrinal and organizational

innovations is still considered beyond dispute.

By the second half of the 20th century, aircraft had

become the preferred evacuation vehicle in western

armies, but use and acceptance came slowly. The first

aircraft did not fly until 1903; however, the future use

of rapid air transport of the sick and wounded had

already been conceived by imaginative minds:
Anesthesia and Perioperative Care of the Combat Casualty

754

Fig. 27-2. Rarely, aircraft were used to evacuate casualties during World War I. Reprinted with permission from

Andrews DR. Helicopter ambulances in critical care. J R

Army Med Corps. 1994:140:22.

Aircraft were used to evacuate casualties during

World War I (Figure 27-2), but the first use of an

airplane specifically modified for casualty evacuation appears to have occurred in 1920 during a

British expedition to what is now Somalia.12 The

mass transportation of sick and wounded by air

first occurred during the Spanish Civil War (1936)

and was carried out by the newly formed German

Luftwaffe. The Condor Squadrons, flying unheated

and unpressurized Junkers JU 52s, transported sick

and wounded back to Germany in a few hours

rather than the days that would have been required

for road, rail, and sea transport.13 The resulting

improvement in the morale of the sick and wounded

were exactly the same as Larrey had described 140

years earlier.14 The full development of German

aeromedical evacuation occurred during the early

years of World War II and especially during the Russo–

German campaign, where the great distances made

evacuation by air especially desirable (Figure 27-3).

During the fall of 1942, far-sighted U.S. military

medical authorities, in recognition of the value of

aeromedical evacuation, established three patient

categories that would justify trans-Atlantic evacuation to the continental United States (CONUS): (1)

emergency cases for whom essential treatment was

not locally available, (2) casualties whose air evacuation the chief surgeon deemed a military necessity,

and (3) casualties who required prolonged hospital

and convalescent care. Nevertheless, by the end of

1943, only 116 patients had been evacuated by air

from the European Theater of Operations. By the

last year of the European war, from 2,000 to 4,000

casualties per month were being evacuated to CONUS by air. This number, although large, needs to

• Jules Verne, in his book Robert le Conquerant,

published in 1854, described the use of an

airship to rescue injured and shipwrecked

seamen.8

• War historians have described the use of

hot-air balloons to evacuate the sick and

wounded during the siege of Paris during

the Franco–Prussian War (1870–1871); unfortunately, however, this romantic description cannot be supported by fact.9

• In the last decade of the 19th century, the

Dutch Surgeon General de Mooy described

and illustrated his concepts of air evacuation (Figure 27-1).

Only 7 years after the Wright brothers’ first flight,

two U.S. Army officers had developed an airplane

for the transport of casualties but the venture did

not receive War Department backing. A second

attempt to obtain U.S. Army funding for the construction of an airplane to transport the severely

wounded was made during a conference in Baltimore, Maryland, only to be followed by an editorial

in the following day’s Baltimore Sun (23 October

1912) that stated: “Surely the hazard of being severely wounded was sufficient without the additional hazard of transportation by airplane.”10 A

similar fate followed the first demonstration flight

in the United Kingdom, which took place in 1913

and lasted exactly 45 seconds. The surrogate

patient’s shouts of fear as he slid gently across the

wing toward the pusher propeller caused a rapid

landing and a complete lack of interest by the army

general staff who were present.11

Fig. 27-1. Aeromedical evacuation as envisioned by Dutch

Surgeon General de Mooy during the late 19th century.

Photograph: Reprinted from Vincent A. Le transport des

blesses par avion. Rev Int Croix Rouge. 1924;6:720–723.
755

Military Medical Evacuation

be put in perspective; casualties returned by air

constituted only about 10% of the total number of

evacuees from Europe. The great majority were

sent home by ship.15

Because of its success in World War II and rapid

developments in aviation technology, aeromedical

evacuation from the hospital level soon came to

dominate all other forms of military medical evacuation. The Secretary of Defense directed in September 1949 that all evacuation of sick and wounded,

both in peace and in war, shall be accomplished by

air whenever aircraft are available and proper medical treatment can be provided to the patient en

route.16 The rationale for this policy, which remains

in effect, is stated in Table 27-1.

The various modes of transportation that are

used in military medical evacuation should not

be thought of as mutually exclusive. In fact, more

than one type of evacuation vehicle is commonly

needed. The complexity and interrelation of evacuation assets was nowhere more obvious than in

the European Theater of Operations at the end of

World War II, in which evacuation was carried out

every using almost every type of land, sea, and air

vehicle (Figure 27-4). Although the U.S. Army’s

experience since World War II has emphasized

evacuation by air at all echelons, the number of

casualties generated in a high-intensity war and the

conditions present in such a war may allow only

for ground evacuation. For example, medical planning for a war between North Atlantic Treaty

Organization (NATO) and Warsaw Pact countries

envisioned the extensive use of hospital trains in

addition to tactical medical evacuation flights

from the corps communication zone. Military anesthesia providers need to maintain a broad perspective when thinking about medical evacuation if for

no other reason than to ensure that the system is

resilient.

Although air transportation has become the dominant mode of evacuation, its utility is based on a

frequently unrecognized assumption; namely, that

a forward air base would always be available for

use as an evacuation and holding center. The British experience in the Falklands War in 1982 showed

that this is not always true. No forward air base was

available initially, which made it impossible to fly

treated casualties out of the combat zone. This

would have been difficult even if an airfield had

been available because the distance between the

Falkland Islands and the nearest British air base, on

Ascension Island, is 4,000 miles (6,400 km). The

solution to the problem was to evacuate casualties

by helicopter to a hospital ship, which then sailed to

neutral territory (Uruguay), from where the casualties were evacuated by air.17

Fig. 27-3. A German aeromedical staging base in the southern portion of the eastern front during 1943. The JU 52s

shown here could carry up to 12 litter casualties; their short takeoff and landing capability were impressive (the

minimum runway length was about 400 m). The relatively idyllic circumstance shown here was exceptional. More

representative of German aeromedical evacuation was the situation at Stalingrad during the great battle in 1942–1943,

in which 25,000 German casualties were evacuated under appalling weather conditions and in the face of overwhelming Soviet military strength. Reprinted with permission from Carell P. Der Russlandkrieg: Fotografiert von Soldaten [in

German]. Frankfurt, Germany: Verlag Ullstein GmbH; 1967: 320–321.
Anesthesia and Perioperative Care of the Combat Casualty

756

The hospital ship was obtained by converting the

cruise liner SS Uganda, the conversion being carried

out in only 4 days. The vessel, which was equipped

with a helicopter landing pad, full hospital facilities, and an intensive care unit, was only 15 minutes’ flying time from the land battles. International Red Cross regulations required that once on

board the hospital ship, all casualties had to be

evacuated from the war zone. Their repatriation

required the good offices of the Uruguayan authorities, who permitted their transfer by sea (in small

survey vessels), over 1,500 km from the Falkland

Islands to Montevideo, for onward air transportation to the United Kingdom. Five hundred eighty

casualties were evacuated by this route.17 The experience of the SS Uganda constitutes one of the few

recent instances in which a hospital ship has been

used as a evacuation vehicle in addition to functioning as a hospital. Much more common is the use of

hospital ships as deployable hospitals.

The British experience in the Falkland Islands

has led to a reevaluation of the role of hospital ships

in any future conflict, resulting in the U.S. Navy’s

converting two supertankers into the hospital ships

Comfort and Mercy, two 1,000-bed hospitals with

full facilities. However, few countries can afford

the luxury of maintaining permanent, fully equipped

hospital ships. A less expensive system has been

developed, whereby hospital facilities such as wards,

operating theaters, radiographic units, laboratories, and intensive care facilities have been modularized, based on the International Standards

Organization’s (ISO’s) standard container. The

number of units can be varied as required and

rapidly installed in any suitable ship.

The ships must have unobstructed deck space,

such as is usually found on fleet auxiliaries, tanklanding ships, or roll on–roll off merchant ferries.

The great advantage of the modular system is that

the vessel can carry out its ordinary task until it is

required for medical duties. The benefits offered by

the Rapid Deployment Hospital Ship program are

low cost, a dual role for the ship, extremely rapid

conversion into the war role, a controlled hospital

environment, and the possibility that any of the

modules can be transferred to land, if required.

This excellent, low-cost facility was used when a

British Naval Auxiliary vessel was converted into a

100-bed facility in a short time and sailed to the

Persian Gulf during the hostilities there (1990–1991).

In describing the evolution of military medical

evacuation in the 20th century, evacuation from

forward hospitals to hospitals in the communication zone or CONUS has been emphasized almost

exclusively. However, regardless of how successfully this link in the evacuation chain functions, it

remains totally dependent on the casualty’s first

having been evacuated from the battlefield. Even

Speed The “Golden Hour” of resuscitation can be better utilized by rapid and safe air transport

of the casualty. The value of rapid evacuation to a Level-1 trauma center has been welldemonstrated in civilian medicine.

Range Transport of casualties over long distances in a relatively short period of time allows

fewer tertiary centers to support several units.

Trafficability Rotor-wing aircraft can pick up patients in relatively inaccessible areas and transport

them quickly and safely. The minimal landing requirements provide this feature.

Flexibility A casualty can be airlifted quickly to that medical installation where appropriate specialized care may be available, thereby bypassing unnecessary delays.

Comfort and Morale Because of the speed and comfort of flight, the soldier knows that if injured, he can be

transported to the appropriate medical treatment facility quickly and in stable condition.

Economy of Resources Because one large hospital is able to accommodate several battle areas, fewer facilities

need to be set up.

TABLE 27-1

ADVANTAGES OF AEROMEDICAL MEDICAL EVACUATION

Advantage Rationale
757

Military Medical Evacuation

Fig. 27-4. This cartoon shows how evacuation was carried out in and from the European Theater of Operations in World

War II. The built-in redundancy allowed for maintenance of the casualty flow even if the activity of one form of

evacuation was impaired (eg, when aeromedical evacuation was hindered by bad weather). It is important to recognize

that evacuation in and from the theater of operations depends totally on the casualty’s arriving at this echelon after

successful evacuation from the unit, division, and corps levels. The symbols indicate army-level, general, and

evacuation hospitals. HU: holding units. Reprinted from Cosmas GA, Cowdrey AE. Medical Service in the European

Theater of Operations. Washington DC: Center of Military History, US Army; 1992: 335.

a By ambulance or hospital train

b By ambulance, hospital train, or

airplane
Anesthesia and Perioperative Care of the Combat Casualty

758

with the field ambulances of Larrey and Letterman,

the casualty would first have to be taken to a collection point from where he could be removed from

the battlefield. Extracting casualties from the battlefield, frequently while under enemy fire—the most

difficult, arduous, and dangerous segment of the

evacuation chain—remained the province of medics, litter bearers, and nonmedical soldiers, who all

depended on human muscle power to move the

casualty. The advent of mechanized warfare in

World War II made possible an alternative approach,

namely, the use of equipment: first, armored fighting vehicles; and second, small, fixed-wing aircraft

and helicopters. The latter had a revolutionary

effect on evacuation because it made possible the

speedy transportation of casualties directly from

the scene of wounding on the battlefield to a surgical hospital.

Helicopter evacuation from the battlefield first

occurred in 1944 in Burma, but first assumed prominence in the Korean War, during which approximately 17,700 casualties were evacuated from the

battlefield to hospitals.18 Although more than

300,000 casualties were evacuated from Korea to

Japan during the Korean War, the true value of air

evacuation was in the timely pick-up and transport

of the soldier from the point of wounding to the

point where he was seen by a medical officer. It was

widely recognized by medical authorities, both

military and civilian, that timely evacuation, together with the use of whole blood and antibiotics,

were the three factors responsible for the low mortality during the Korean War.

During the Vietnam War, between 850,000 and

900,000 allied military personnel and Vietnamese

civilians underwent aeromedical evacuation. At

least 90% of all hospitalized U.S. Army battle casualties were evacuated by helicopter at one time or

other during their treatment.18 There can be no

doubt that the helicopter, by making unnecessary

many long and difficult litter carries as well as

uncomfortable trips in ground ambulances, made

life much more tolerable for both casualties and

medics (Figure 27-5).

Nevertheless, helicopter evacuation of casualties

directly from the battlefield was not without drawbacks. For example, when compared with fixedwing aircraft, helicopters have limited operational

ranges. On an extensive battlefield such as characterized the Persian Gulf War,direct helicopter evacuation from the site of injury to the hospital level is

usually impractical. In addition, darkness and

weather conditions at times interfere with

aeromedical evacuation. More importantly, helicopter evacuation from the battlefield can be very

dangerous. It has been estimated that one third of

all air ambulance pilots in the Vietnam War sustained either battle or nonbattle injuries, and medical evacuation helicopters sustained more than three

times more battle damage than helicopters used in

combat and combat support missions.18 Although

regulations initially precluded making casualty pickups from landing zones that were subject to enemy

fire, this became commonplace in both the Korean and

Vietnam wars. The heroism of helicopter crews made

possible the evacuation of casualties that in many

instances, in retrospect, seems impossible.

Even so, helicopter evacuation from the highintensity battlefield is probably suicidal. In fact,

U.S. Army regulations do not foresee casualty extraction by helicopter occurring forward of the battalion aid station when enemy air-defense artillery

capabilities are substantial; thus, the need for evacuation vehicles capable of functioning far forward

Fig. 27-5. A scene from the Somalia

peacekeeping operation. A casualty

is being removed from a UH-1 medical evacuation helicopter while a UH60 hovers in the background. The

latter is now the US Army’s primary

air ambulance, replacing the former,

which has served with distinction

since its introduction in 1959. The

UH-60 has greater range and speed,

and superior aivonics compared with

the UH-1 but, suprisingly, can carry

no more casualties. Photograph: Public Affairs, Office of The Surgeon General, US Army.
759

Military Medical Evacuation

Fig. 27-6. Evacuation during an armored battle fought in central Russia during summer, 1943. The armored unit’s

medical officer rode into battle in the tank shown on the left and was accompanied by an armored personnel carrier,

which was used to evacuate the casualty. First aid and preparation of the casualty for evacuation took place in the open.

Although the casualty was protected from small-arms fire and fragments from shells during evacuation, the small

internal volume of the armored personnel carrier precluded effective ongoing care. Futhermore, the separation of the

physician and the casualty during evacuation no doubt resulted in increased mortality and morbidity. Reprinted with

permission from Pielkalkiewicz J. Unternehmen Zitadelle [in German]. Bergisch Gladbach, Germany: Gustaf Lübbe

Verlag GmbH; 1983.

under enemy fire.2(p4-12) The precedent for the use of

armored fighting vehicles for this purpose dates

from early in World War II, when German armored

formations used half-track vehicles for casualty

evacuation (Figure 27-6). More recently, many other

armies have used armored personnel carriers for

evacuating casualties under enemy fire. The Israelis have even used their main battle tank—the

Merkava—for this purpose. The Merkava’s engine

is in the front, which leaves a space in the rear—

accessed by an armored door—that can be used for

carrying several casualties.

ground, with the remaining 10% by air (—RFB,

personal observation, 1994). In a low-intensity war,

most evacuation can be expected to be by air. Evacuation at the unit level is regulated by the battalion

surgeon or the medical company commander; at the

division level, by the division medical operations

center.2(p4-2)

Ground Evacuation

As previously indicated, aerial transport may

not be feasible because of enemy action. Furthermore, bad weather, darkness, and distance may

preclude aeromedical evacuation. Ground ambulances may be used at these times. These ambulances, which are organic (ie, intrinsic; included in

the Table of Organization and Equipment) to the

U.S. Army Medical Department units that are responsible for transporting the sick and wounded,

The schematic diagram that is part of the front

matter of this book shows the organization for evacuation as it existed in the U.S. Army at the time of

publication. For purposes of this chapter, the system used to evacuate sick and wounded soldiers

will be studied in three segments: (1) the unit (ie, the

medical platoon) and the division level, (ie, the

medical company or medical battalion, which usually have no surgical capabilities); (2) the corps

level and the communication zone, which contain

the deployable hospitals; and (3) the domestic system, which is operated by the U.S. Air Force.

Unit and Division Levels

Evacuation at the unit level can be by ground or

by air. The type of vehicle used depends on the

warfighting scenario. In a high-intensity war, it is

likely that 90% of casualty evacuation will be by

LOGISTICAL AND OPERATIONAL ASPECTS
Anesthesia and Perioperative Care of the Combat Casualty

760

have the basic supplies and are staffed with ambulance personnel qualified in basic emergency medical care and treatment procedures. An ambulance

crew consists of a driver and an additional soldier,

both of whom are medical aidmen. Current ground

ambulances include the following vehicles2(pp10-1–10-16):

• M1010 truck ambulance, 11⁄4 ton 4 x 4. This

truck is designed to transport the sick and

wounded and is the standard field ambulance of medical units at the division and

higher-level units where suitable roads exist. The patient compartment is separated

from the remainder of the vehicle and has a

heater and a surgical light. The capacity is

4 litter patients, or 8 to 10 ambulatory patients, or a combination of litter and ambulatory patients (eg, 2 litter and 5 ambulatory patients).

• High-mobility, multipurpose, wheeled vehicle (HMMWV, M996 and M997) truck

ambulance, 4 x 4, armored tactical vehicles.

The HMMWV is designed to be used crosscountry and over all types of terrain. Depending on the configuration, the vehicle can

carry 2 to 4 litter patients, or 6 to 8 ambulatory casualties, or a mixture of litter and

ambulatory casualties. These vehicles can

be modified for operation in a nuclear, biological, or chemical warfare environment.

• M113 carrier, personnel, full-tracked, armored. The M113 can carry up to 10 ambulatory or 4 litter patients.

The M792 (Gamma Goat), M170, and M718 evacuation vehicles are being phased out of the U.S. Army’s

inventory. Any military vehicle may be adapted for

carrying patients as the situation allows, but safety

and stability during transport are important priorities that need to be satisfied by any putative ambulance.

Air Evacuation

An assigned mission of the U.S. Army is to provide air transportation for the sick and wounded

within the combat zone. The major objective of air

transportation is the expedient delivery of the casualty to the care level necessary for survival. The

flexibility and rapid deployment of air services make

this an optimal method of delivery. Air transport

involves the use of either fixed- or rotor-wing aircraft.

Organization of U.S. Army Air Evacuation

A soldier injured in a forward area may initially

receive first aid from an aidman. Then the soldier

may be transported by ground to the battalion aid

station, where the injury is reassessed; if evacuation

is necessary, it is the U.S. Army’s responsibility to

provide appropriate ground or air evacuation. The

latter is usually provided by the medical air ambulance company. The medical company’s air ambulance is normally assigned to the corps medical

brigade and is attached to the medical evacuation

battalion for command and control.2(p3-7)

The capabilities of the medical air ambulance

company include

• aeromedical evacuation of critically wounded or other patients;

• extrication and then air evacuation of personnel from crashed aircraft;

• emergency aid at air-crash sites, in-flight

medical treatment, and surveillance of patients en route to treatment facilities;

• expeditious delivery of medical personnel

and material to meet emergency treatment

requirements within a combat zone; and

• in-flight emergency medical care.

The core of the air ambulance company is its air

ambulance platoon. Military physicians need to be

aware of the composition and skill level of this

platoon. Each consists of a platoon leader, two

section leaders, nine evacuation pilots, one platoon

sergeant, six air ambulance aidmen, six crew chiefs,

and one voice-radio operator. Each platoon is authorized six UH-60A helicopters. Each helicopter

has an assigned crew consisting of a crew chief, two

pilots, and an air ambulance aidman. All are proficient in emergency medical treatment. Although

each air ambulance has a capacity for six litter

patients or nine ambulatory patients (the UH-1), or

four litter and seven ambulatory patients (the UH60A), the combat load for each is three litter and

four ambulatory patients.2(p10-27)

The situation may occur when nonmedical aircraft such as the U.S. Army’s CH-47 Chinook will be

used for evacuation at the division level. This

helicopter can carry up to 24 litter patients.

Only approved and tested equipment may be

taken aboard aircraft, and each type of aircraft has

its own list of approved equipment. Medical personnel should consult with the crew chief or senior

medic of the particular aeromedical evacuation
761

Military Medical Evacuation

ambulance to ascertain what equipment is presently available and approved.

Air Ambulance Operations

Air ambulances are used as far forward as possible and as the numbers of combat casualties allow.

Ambulances should be used only if the landing

zone is both free of hostile fire and secure. If it is

not, the pilot must be notified. The base of operations must be located and operated so that it can

respond as quickly as possible when there are casualties on the battlefield. In the absence of clear

guidelines as to the casualty’s destination, the pilot

is the final authority.

All medical officers of deployable units should

know how to arrange aeromedical evacuation. FM

8-10-6 should be consulted for a detailed description of the official procedure; a brief overview follows. Requests for air ambulance evacuation must

contain concise, accurate, and reliable information

so that appropriate equipment can be provided and

flights planned. The commander of the air ambulance team supporting the division decides whether

to accept the mission, based on meteorological conditions or the availability of aircraft. All U.S. Army

aeromedical evacuation requests should provide

information in the sequence provided in FM 8-10-6

(Exhibit 27-1).

Assignment of Medical Evacuation Priority

FM 8-10-6 specifies the following categories of

precedence and the criteria used for their assignment:

Priority I—URGENT is assigned to emergency cases

that should be evacuated as soon as possible and

within a maximum of 2 hours to save life, limb, or

eyesight; to prevent complications of serious illness; or to avoid permanent disability.

Priority IA—URGENT-SURG is assigned to patients who must receive surgical intervention far forward to save life and stabilize for further evacuation.

Priority II—PRIORITY is assigned to sick and

wounded personnel requiring prompt medical care.

This precedence is used when (a) the individual

should be evacuated within 4 hours or his medical

condition could deteriorate to such a degree that he

will become an URGENT precedence, or (b) requirements for special treatment are not available locally,

or (c) will suffer unnecessary pain or disability.

Priority III—ROUTINE is assigned to sick and

wounded personnel requiring evacuation but whose

condition is not expected to deteriorate signifiEXHIBIT 27-1

SEQUENCE OF INFORMATION

REQUIRED IN U.S. ARMY AEROMEDICAL EVACUATION REQUESTS

LINE 1: Location of pick-up site

LINE 2: Radio frequency, call sign and suffix

LINE 3: Number of patients by precedence, as

described in FM 8-10-6 (p7-1)

LINE 4: Special equipment required (eg,

ventilator)

LINE 5: Number of patients and type of injury

LINE 6: Security of pick-up site

LINE 7: Method of marking pick-up site

LINE 8: Patient nationality and status

LINE 9: Nuclear, biological, and chemical

contamination

Adapted from Department of the Army. Field Manual 8-

10-6. Medical Evacuation in a Theater of Operations. Washington DC: Headquarters, DA; 31 October 1991: pp 7-3–7-5.

cantly. The sick and wounded in this category

should be evacuated within 24 hours.

Priority IV—CONVENIENCE is assigned to patients for whom aeromedical evacuation is a matter

of medical convenience rather than necessity.2(p7-1)

Civilian Approaches to the Assignment of

Evacuation Priority

The assignment of evacuation priorities according to FM 8-10-6 is, by its very nature, subjective.

In an effort to bring objectivity to the determination

of the need for helicopter evacuation to a trauma center, civilian emergency medical systems

have adopted the use of triage scoring systems.

The civilian approach needs to be understood

by military anesthesiologists because a modification may be applicable to military medical evacuation:

• The Trauma Score (Exhibit 27-2) is a composite that includes measures of the status

of the cardiovascular, respiratory, and central nervous systems. (It incorporates the
Anesthesia and Perioperative Care of the Combat Casualty

762

A. Respiratory Rate

Number of respirations in 15 s, multiplied by 4 10–24 4

25–35 3

> 35 2

< 10 1

0 0

A.

B. Respiratory Effort

Normal Normal 1

Shallow—markedly decreased chest movement or air Shallow 0

exchange

Retractive—use of accessory muscles or intercostal Retractive 0

retraction

B.

C. Systolic Blood Pressure

Systolic cuff pressure, either arm, auscultate or palpate > 90 4

70–90 3

50–69 2

< 50 1

No carotid pulse 0 0

C.

D. Capillary Refill

Normal—forehead, lip mucosa, or nail-bed color Normal 2

refills in 2 s

Delayed—more than 2 s of capillary refill Delayed 1

None—no capillary refill None 0

D.

EXHIBIT 27-2

TRAUMA SCORE USED IN CIVILIAN EVACUATION

Trauma Score Component Value Points Score

Reprinted with permission from Champion HR, Sacco WJ, Carnazzo AJ, et al. Trauma score. Crit Care Med. 1981;9:672.

Total Glascow

E. Glasgow Coma Scale (GCS) Value Coma Scale Points Score

1. Eye Opening

Spontaneous 4 14–15 5

To voice 3 11–13 4

To pain 2 8–10 3

None 1 5–7 2 E.

2. Verbal Response

Oriented 5

Confused 4

Inappropriate words 3

Incomprehensible words 2

None 1

3. Motor Response

Obeys commands 6

Purposeful movement (pain) 5

Withdraw (pain) 4

Flexion (pain) 3

Extension (pain) 2

None 1

Trauma Score

Total GCS points (1 + 2 + 3) (Total points A + B + C + D + E)
763

Military Medical Evacuation

Reprinted with permission from Clemmer TP, Orme JF

Jr, Thomas F, et al. Prospective evaluation of the CRAMS

scale for triaging major trauma. J Trauma. 1985;25:189.

Circulation

2: Normal capillary refill and blood pressure

> 100 mm Hg systolic

1: Delayed capillary refill or blood pressure

85–99 mm Hg systolic

0: No capillary refill or blood pressure < 85

mm Hg systolic

Respiration

2: Normal

1: Abnormal (labored, shallow, or rate > 35)

0: Absent

Abdomen

2: Abdomen and thorax not tender

1: Abdomen and thorax tender

0: Abdomen rigid, thorax flail, or deep

penetrating injury to either chest or

abdomen

Motor

2: Normal (obeys commands)

1: Responds only to pain, no posturing

0: Postures or no response

Speech

2: Normal (oriented)

1: Confused or inappropriate

0: Unintelligible or no sounds

 Total CRAMS Score

Recommended equipment for civilian helicopter

evacuation is shown in Exhibit 27-4. A simplified

triage flow sheet (Figure 27-7) and a recommendation for helicopter transport at all times (Exhibit 27-

5)21 are also included to allow some familiarity with

civilian decision making. Additional recommendations have been set forth for the transport of the

critically ill patient and have been reviewed and approved by The Association of Air Medical Service.22

Corps and Communications Zones: Zone of the

Interior

Much of the medical evacuation that occurs at the

corps level and above will involve the U.S. Air

Force. However, the corps level medical evacuation battalion has as one of its missions the task of

evacuating casualties from the division to the corps

level, and does this by using the army’s ground or

air assets.

Evacuation from the division is regulated by

the division Medical Operations Center and the

medical group Medical Regulations Officer.2(p4-2)

Evacuation from the corps level to the communication zone and higher is the mission of the Military

Airlift Command of the U.S. Air Force. Medical

regulating at this level proceeds from the patient

administrator of a given hospital to the medical

group and medical brigade Medical Regulating

Office to the theater-level Joint Medical Regulating

Office. Medical regulating for evacuation from the

communications zone to the zone of the interior is

carried out by the Armed Services Medical Regulating Office.

It is important that military anesthesiologists

recognize that when the casualty initially enters the

U.S. Air Force’s medical evacuation system, he will

be at a Mobile Aeromedical Staging Facility (MASF).

The function of this unit is to collect casualties,

not to provide treatment. Physicians are not assigned to a MASF and casualties should not be sent

there unless they are in stable condition. Furthermore, the MASF does not have a holding capability;

patients are not to remain there longer than 6

hours.2(p6-9)

Tactical Evacuation System

The tactical evacuation system provides for the

airlift of patients within the corps level and from the

corps level to the communication zone. Most of

these casualties will have had initial surgery and

should be in stable condition. U.S. Air Force guidance indicates that mission duration will not exceed

Glasgow coma scale as its central nervous

system component.) The best feature of the

Trauma Score is that it measures the physiological state at the scene of the injury.

Patients who require prompt diagnosis and

definitive care at a Level 1 trauma center

are those with a score of 12 or less.19

• The CRAMS scale was developed by S. P.

Gormican in 1982 and modified by T. P.

Clemmer in 1985 (Exhibit 27-3).20 It is a simple

and easy scale to remember, with the letters

of the acronym representing circulation, respiration, abdomen, motor, and speech.

EXHIBIT 27-3

MODIFIED CRAMS SCALE USED IN

CIVILIAN MEDICAL EVACUATION
Anesthesia and Perioperative Care of the Combat Casualty

764

EXHIBIT 27-4

RECOMMENDED CIVILIAN HELICOPTER CHECK LIST

*Nitroglycerin in 1,2,3-propanetriol trinitrate, manufactured by Du Pont Multi-Source Products, Garden City, NY

†Syrup of Ipecac, manufactured by Roxane Laboratories, Inc, Columbus, Oh

‡Manufactured by Protocol Systems, Inc, Beaverton, Ore

§Kendrick Extraction Device, manufactured by Medix Choice, Santee, Calif

¶Portable: Continuous and Programmable Intermittent Suction System, Model 326/326M, manufactured by Impact Instrumentation, Inc, West Caldwell, NJ

In Side Wall Blue Pouches:

1 pair wrist restraints

1 roll 2-in. cloth tape

2 oral airways (small, medium)

1 30-mL syringe

1 10-mL syringe

2 pairs eyeglasses

Masks and gloves

In Front Wall Pockets:

2 survival kits

2 life vests

Doppler flow probe and acoustic coupler

2 lithium-powered batteries

Obesity blood-pressure cuff

Large adult blood-pressure cuff

Passenger guide

On Side Wall:

Suction cannister with suction tubing and

yankeur

2 oxygen regulators

Personal mask resuscitation bag, with mask

In Clam Shell:

2 head rolls

Cervical collars (small, medium, large)

1 spider strap

Pediatric immobilizer with pump

In Airway Seat:

Large survival kit

1 life vest

In Side Seat Drawer:

4 D-cell batteries

2 reflective vests

1 syringe pump

1 syringe pump charger

2 spare stretcher brackets

1 flashlight

1 L normal saline

500 mL Tridil*

Charcoal and ipecac syrup†

Foam ear plugs

Charger for PROPAC‡ monitor and pulse

oximeter

Between Bench and Side Seat:

Military antishock trousers bag

In Side Rear Pouch:

1 trauma dressing

1 sterile drape

2 reflective vests

1 camp light

Under Bench Seat:

Linen

Pneumatic shock garments, adult and pediatric,

with pump

Clipboard with flight charts

Under Side Seat:

Elastic bracket for lithium-powered battery

On Wall Next to Side Seat:

Backup stretcher

KED extraction splint§

Scoop stretcher

Blue interhospital patient-attendant bag

Red scene bag

Behind Side Seat:

3 oxygen tanks

With Stretcher:

Oxygen tank and regulator

PROPAQ monitor with cables and cuff

Also Aboard Helicopter:

1 spare headset

2 fire extinguishers

Portable, free-standing suction unit¶

Suction kits and 1 yankeur

Charger for lithium-powered battery
765

Military Medical Evacuation

Glasgow coma score < 13 or

Systolic blood pressure < 90 or

Respiratory rate < 10 or > 29

No

Penetrating injury to chest, abdomen, head, neck, and groin

Two or more proximal long-bone fractures

Combination with burns of > 15% of the body surface or of the face or

airway

Flail chest

Evidence of high-speed impact:

Falls of 20 ft or more

Crash speed 20 mph or more; 20 in. deformity of automobile

Rearward displacement of front axle

Passenger compartment intrusion 15 in. on patient side of automobile;

20 in. on opposite side of automobile

Ejection of patient

Rollover of automobile

Death of occupant in same automobile

Pedestrian hit at 20 mph or more

Yes

Age < 5 or > 56

Known cardiac or respiratory disease (which lower the threshhold of severity requiring care in a trauma center)

Consider taking to trauma center

for injury of moderate severity

Reevaluate following consultation with

appropriate specialists

When in doubt, transport to a trauma center

Measure vital signs and

level of consciousness

Yes

Transport to

trauma center

Assess anatomy of injury

and mechanism of injury

No

Yes No

Fig. 27-7. Civilian triage decision scheme. In stage 1, if easily determined clinical indices such as the Glasgow coma score,

systolic blood pressure, and respiratory rate are abnormal, the patient should be flown directly to a trauma center. Stage

2 is implemented in patients in whom these indices are not grossly abnormal. The anatomical location of the injury and its

mechanism are used as discriminators. In stage 3, extremes of age and the known presence of cardiopulmonary disease are used

as further triage discriminators. Adapted with permission from Champion HR. Helicopter triage. Emerg Care Q. 1986;2:13–21.

Stage 1

Stage 3

Stage 2

Transport to

trauma center
Anesthesia and Perioperative Care of the Combat Casualty

766

EXHIBIT 27-5

SIMPLIFIED CIVILIAN EVACUATION

POLICY

A helicopter should be used for patient transport under any of the following conditions:

Urban and suburban environments

Transport time to the trauma center > 15 min by

ambulance

Ambulance transport impeded by access to or

egress from the accident scene

Presence of multiple casualties

Rural environment

Time to local hospital via ambulance > time to

trauma center via helicopter

Wilderness rescue

Reprinted with permission from Champion HR. Helicopter triage. Emerg Care Quart. 1986;2:20.

4 hours. The most commonly used aircraft is the C130 Hercules (Figure 27-8).2(p10-45) The C-130 is a

long-range, high-wing, four turboprop–engine aircraft. The fuselage is divided into the cargo compartment and the flight deck. It can be fully pressurized, heated, and air conditioned. The C-130

can maintain a sea-level cabin pressure at an altitude up to 19,000 ft and an 8,000-ft cabin pressure at

an altitude of 35,000 ft. It can land and take off

on runways as short as 600 m, a capability that

allows for rapid transportation of personnel and

equipment to and from the battlefield. The C-130

can readily be configured for aeromedical evacuation by using seat and litter provisions stowed in

the cargo compartment, but military anesthesia

providers should not expect to find extensive resources available for treatment. Depending on inherent equipment and the model of the aircraft,

it can hold a maximum of 74 litter patients, 92

ambulatory patients, or various combinations (Figure 27-9).

Strategic Evacuation System

The mission of the strategic evacuation system is

to provide controlled evacuation of stable patients

to medical treatment facilities that are located outside the theater of operations—frequently in CONUS. U.S. Air Force guidance on mission duration

Fig. 27-9. This photograph, taken during an exercise in

1980, shows the extremely tight space available for individual casualties. The space and the sparse medical equipment provided markedly limit the provision of in-flight

medical care. Photograph: Defense Audio-Visual Agency,

Still Media Depository,Washington, DC.

Fig. 27-8. A C-130 Hercules taking off somewhere in the

Kuwaiti Theater of Operations during the Persian Gulf

War. The original design of the C-130 dates from 1951.

The rugged construction of these aircraft allows them to

use unprepared runways, as are found forward on the

battlefield. Photograph: Defense Audio-Visual Agency,

Still Media Depository, Washington, DC.
767

Military Medical Evacuation

a b

Fig. 27-10. The C-141 Starlifter (a) and its loading ramp (b). This aircraft was the mainstay of the US Air Force’s strategic

aeromedical evacuation system during both the Vietnam and the Persian Gulf wars. Photographs: Courtesy of

Lieutenant Colonel Charles Beading, MD, Medical Corps, US Air Force, Flight Surgeon, Uniformed Services University of the Health Sciences, Bethesda, Md.

Fig. 27-11. In-flight conditions for casualties aboard a C-141 during a strategic aeromedical evacuation. Access to

patients and the availability of medical equipment are superior to that on the C-130. Photograph: Courtesy of

Lieutenant Colonel Charles Beading, MD, Medical Corps, US Air Force, Flight Surgeon, Uniformed Services University of the Health Sciences, Bethesda, Md.

is 7 to 14 hours. The aircraft currently used is the C141 Starlifter (Figure 27-10).

2(p10-46) The C-141 is a

long-range, high-speed, high-altitude aircraft designed for the airlift of combat support equipment,

troops, or aeromedical evacuation patients. It is

powered by four jet engines, cruises at 550 mph at

an altitude of 30,000 ft, and has a range of 5,250

miles. When used for aeromedical airlift, a selfcontained comfort pallet can be placed in the forward

section of the cargo compartment. Conditions aboard

a typical strategic aeromedical evacuation flight during the Persian Gulf War era are shown in Figure
Anesthesia and Perioperative Care of the Combat Casualty

768

a b

Fig. 27-12. The C-9 Nightingale (a), a modified version of the commercial DC-9 and the only US Air Force aircraft

especially designed for aeromedical evacuation. (b) The loading ramp. Photographs: Courtesy of Lieutenant Colonel

Charles Beading, MD, Medical Corps, US Air Force, Flight Surgeon, Uniformed Services University of the Health

Sciences, Bethesda, Md.

27-11. Maximum capacity of the aircraft is 103

litters or 147 ambulatory patients, or various combinations of litter and ambulatory patients. The conditions are much better than in the C-130. Patients

are not overcrowded, hot meals are provided, and

the cabin temperature is better controlled than in

tactical aircraft. Oxygen and electrical outlets permit the use of complex medical equipment en route.

However, dehydration may occur because the flights

are long and the ambient humidity is low (5%–30%).

There has been recurrent interest in configuring

and outfitting a small number of C-141s as flying

intensive care wards.

Domestic Aeromedical Evacuation System

The U.S. Air Force’s daily system of flights within

CONUS has flight crews and aircraft dedicated to

aeromedical evacuation of military casualties. The

aircraft currently used is the C-9 Nightingale, which

is a modified version of the commercial DC-9.2(p10-45)

The T-tailed aircraft is powered by twin, aft-mounted

jet engines and cruises at 500 mph. Its range exceeds 2,300 miles. The C-9 is the only U.S. Air Force

aircraft specifically designed for aeromedical evacuation. An integral folding ramp enables efficient

enplaning and deplaning of litter patients (Figure

27-12). The C-9 can hold a maximum of 40 litter

patients, 40 ambulatory patients, or a variety of

combinations of litter and ambulatory patients (Figure 27-13). The environment on board is comparable to first-class accommodations on a commercial airline. Most specialized equipment available

on a hospital ward can be provided on a C-9, including isolation and humidity control.

Although the domestic system is in operation daily,

it is during emergencies, when military casualties of

accidents and disasters require evacuation to specialized hospitals within CONUS, that its function is most

clearly illustrated, as in the following incident.

The air force’s domestic aeromedical evacuation

system was activated in March 1994 after two army

training planes (a four-engine turboprop C-130

Hercules transport plane and a single-engine F16D) crashed and burned while attempting to land

at Pope Air Force Base, North Carolina. Twentythree paratroopers died and 83 others sustained

burns or other injuries in the accident. The severely

burned survivors were aeromedically evacuated to

the burn center at Brooke Army Medical Center,

Fort Sam Houston, San Antonio, Texas.23

While the injured were being triaged and treated at

Womack Army Medical Center, Fort Bragg, North

Carolina; [civilian hospitals in Fayetteville and

Chapel Hill]; and Portsmouth [Virginia] Naval

Hospital; the Aeromedical Evacuation Coordination Center (57th Aeromedical Evacuation Squadron) at Scott Air Force Base (AFB), Illinois...was

dispatching two C-9As and medical crew members

to Fayetteville.

In the meantime, the Air Education and Training

Command (Randolph AFB, San Antonio [Texas])

provided a twin-jet T-43 A...to fly a burn team from

Brooke Army Medical Center to Pope AFB.

. . . .

[T]he first C9-A departed Pope AFB the following

morning for Kelly AFB, San Antonio, with 11 patients on litters, nine of whom were on ventilators.

All had second- and third-degree burns covering

from 30% to 80% of their bodies.... The second C9A made the flight about 5 hours later with nine
769

Military Medical Evacuation

a

c

Fig. 27-13. (a, b, and c) Patient conditions aboard the C-9 Nightingale.

Photographs: Courtesy of Lieutenant

Colonel Charles Beading, MD, Medical Corps, US Air Force, Flight Surgeon, Uniformed Services University

of the Health Sciences, Bethesda, Md.

b
Anesthesia and Perioperative Care of the Combat Casualty

770

EXHIBIT 27-6

U.S. AIR FORCE CLASSIFICATION OF PATIENTS SCHEDULED FOR AEROMEDICAL

EVACUATION

Sources: (1) Department of the Army. Field Manual 8-10-6. Medical Evacuation in a Theater of Operations. Washington DC:

Headquarters, DA; 31 October 1991: p F-1. (2) Department of the Air Force. Physicians’ Roles and Responsibilities in Aeromedical

Evacuation. Washington, DC: Secretary of the USAF; 1995: in press. Air Force Joint Manual 41-306.

Class 1. Neuropsychiatric Patients

lA. Severe psychiatric litter patients requiring the use of restraining apparatus, sedation, and close

supervision at all times.

lB. Psychiatric litter patients of intermediate severity requiring tranquilizing medication or sedation,

not normally requiring the use of restraining apparatus, but who react badly to air travel or who

may commit acts likely to endanger themselves, others, and/or the safety of the aircraft. Restraining apparatus should be available for use.

lC. Psychiatric walking patients of moderate severity who are cooperative and who have proved

reliable under observation.

Class 2. Litter Patients (Other Than Psychiatric)

2A. Immobile litter patients unable to move about of their own volition under any circumstances.

2B. Mobile litter patients able to move about of their own volition in an emergency.

Class 3. Walking Patients (Other than Psychiatric)

3A. Nonpsychiatric and nonsubstance abuse patients who require medical treatment, assistance, or

observation en route.

3B. Recovered patients who are returning to their units and require no medical attention en route.

3C. Ambulatory drug or alcohol substance-abuse patients.

Class 4. Infant Category

4A. Infants under 3 years of age, occupying a seat or in a bassinet or car seat secured in an ambulatory

seat.

4B. Recovered infants under 3 years of age, occupying a seat or in a bassinet or car seat secured in an

ambulatory seat.

4C. Infants in an incubator.

4D. Infants younger than 3 years of age on a litter.

4E. Outpatients under 3 years of age on a litter for comfort.

Class 5. Outpatient Category

5A. Ambulatory outpatients, non psychiatric and non substance abuse, who are traveling for an

outpatient visit and do not require a litter or medical assistance in flight.

5B. Ambulatory drug- or substance-abuse outpatients going for treatment.

5C. Psychiatric outpatients going for treatment.

5D. Outpatients on a litter for comfort or safety.

5E. Returning outpatients on a litter for comfort or safety.

5F. Other returning outpatients.

Class 6. Attendant Category.

6A. Medical attendants, either physician, nurse, or technician, who are assigned to give specialized

medical treatment or nursing care to a particular patient.

6B. Nonmedical attendants, either relatives or friends, who may assist with the patient’s care and who

may also require support.
771

Military Medical Evacuation

Altitude (meters) 

Barometric Pressure (mmHg) 

0

100

200

300

400

500

600

700

800

0 1500 3000 4500 6000 7500 9000 10500 12000

patients on litters, five of whom were on ventilators. Two patients already had undergone leg amputations.

. . . .

[T]he flights were cleared to fly directly to San

Antonio and thus were able to do so in less than 2

hours.23(p1225)

Military anesthesiologists need to be aware that

to overcome shortfalls of strategic evacuation capability during a major war, the air force, in conjunction with a number of airlines and the U.S. Department of Transportation, has expanded the existing

Civilian Reserve Air Force program to provide aircraft dedicated to aeromedical evacuation. The

primary aircraft to be provided to support aeromedical airlift is the B-767. Once activated, each B767 would be reconfigured from its civilian passenger configuration to an aeromedical configuration

in about 18 hours.

Because casualties who enter the U.S. Air Force

medical evacuation system during wartime should

be medically stable, the prioritizing of precedence

for picking up and moving casualties is more commonly applicable to emergency situations such as

peacetime disasters24:

• URGENT: pick up immediately

• PRIORITY: pick up within 24 hours

• ROUTINE: pick up within 72 hours

The air force places considerable importance on the

classification of patients to be evacuated (Exhibit

27-6).2(pF-1) The great majority of combat casualties

will be placed into Classes 2A and 2B.

MEDICAL IMPLICATIONS OF BIOPHYSICAL EFFECTS OF AEROMEDICAL EVACUATION

Many potential problems are associated with

aeromedical evacuation, but most of the unique

threats are specific to long-range flight at high altitude and are a consequence of human adaptations

to life at sea level. The modern jet must fly at the

highest possible levels (9,000–12,000 m) for reasons

of speed, fuel economy, and comfort. At 12,000 m

the barometric pressure is only 140 mm Hg. At this

level, the partial pressure of oxygen is approximately 30 mm Hg, which cannot sustain human life.

Jet aircraft can operate at such altitudes only because the pressurized cabin was developed, which

maintains ambient cabin altitude at a barometric

pressure equivalent to that found between 1,500

and 2,600 m. Despite all the problems of living in a

strange environment, “aeromedical transport of patients presents no problems so long as one remembers

that man is adapted for life at sea level.”25(p237)

Barometric Pressure

Barometric pressure falls as a function of height

above the surface of Earth (Figure 27-14). This fact

explains not only the etiology of hypoxia at altitude

Fig. 27-14. Barometric pressure as a

function of altitude.

0 1,500 3,000 4,500 6,000 7,500 9,000 10,500 12,000

Altitude (meters)

0

100

200

300

400

500

600

700

800

Barometric Pressure (mm Hg)
Anesthesia and Perioperative Care of the Combat Casualty

772

but also why gas trapped within body cavities, as well

as gas used to fill medical devices, can constitute a

significant hazard to casualties undergoing aeromedical evacuation. The effect of falling barometric

pressure is understandable in terms of the gas laws of

Boyle and Dalton. Boyle’s law states that at a constant temperature, the volume of a gas is inversely

proportional to the pressure to which it is subjected.

As altitude increases in an unpressurized aircraft

and as barometric pressure decreases, gas in a closed

or semiclosed space expands. All common drug

vials, albumin infusions, and medical containers

act like closed spaces when taken to altitude.

Patients with pneumothorax, bowel obstruction, and

other conditions in which gas is trapped in a closed space

are at risk. The most serious problem occurs in

casualties who have an untreated pneumothorax.

In properly treated casualties, a chest tube attached

to a one-way valve will have been inserted and left

in place until the air leak has sealed. However, if

undetected prior to evacuation, the volume of

trapped gas will increase as the ambient pressure

falls, producing a degree of cardiorespiratory embarrassment that may require urgent decompression. Therefore, in cases of suspected pneumothorax,

it is essential to obtain a chest radiograph prior to

evacuation. It is much easier for the physician and

safer for the patient to delay the evacuation, or, if

evacuation must take place, to insert the chest tube,

before departure. The alternative is being presented with the need to perform an arduous and

dangerous act during the flight.

Expansion of gas in the intestinal tract can also

give rise to problems. Although only small volumes are involved, there is a theoretical risk that

the expansion of the gas could produce damage

to anastomotic suture lines following intestinal

surgery or dehiscence of the abdominal incision.

One of the earlier tenets of air evacuation was

to defer moving recently operated patients for at

least 14 days although, based on Israeli experience

with aeromedical evacuation starting with the Yom

Kippur War and continuing through the Lebanon

War of 1982, recent abdominal surgery is no longer

considered a contraindication if the gastrointestinal tract is kept decompressed with a nasogastric

tube.26

In a group of patients with paralytic ileus who

were treated with hyperbaric oxygen, studies have

shown that high concentrations of oxygen can reduce abdominal distension. It is possible to move

casualties who have had recent operations if the

patients receive 100% oxygen (via mask or endotracheal tube) during the flight.27

Of paramount importance is the status of the endotracheal tube or tracheostomy cuff balloon, which will

expand at increasing altitude. This expansion can

preclude patient ventilation and cause pressure necrosis of the tracheal wall. Although the volume of air

used to inflate the cuff of an endotracheal tube used

for ventilatory support is small, the changes in volume can produce complications even when using the

modern, low-pressure, high-volume cuffed endotracheal tube. It is essential that the cuff be inflated with

either saline or water to overcome this further complication of a change in ambient pressure.

During long-range medical evacuation, many

casualties will be receiving intravenous fluids, the

daily requirements of which have been carefully

calculated. The fall in ambient pressure in the aircraft cabin can cause an appreciable acceleration of

the rate of infusion because the volume of air in the

intravenous infusion set will increase with increasing altitude. A drip chamber with a total volume of

9 mL that contains 2 mL of fluid at sea level will be

completely empty at 2,000 m. It is therefore essential to monitor the drip rate, if infusion pumps are

not in use. Care must be taken to ensure that adequate replacement fluid volumes are available (it is

very difficult to obtain extra supplies while flying at

10,000 m). A final precaution to be observed is that

all infusion fluid should be carried in flexible plastic containers, not in glass bottles, which could

explode during the flight.

The problems associated with expansion of gas

in closed spaces is found in air-pressure splints

including pneumatic antishock garments (PASGs)

and even certain types of stretchers. As ambient

pressure decreases, the transmural pressure across

the wall of the PASG will increase, causing it to

inflate and thereby compress the casualty’s incarcerated extremities and lower trunk. This effect is

especially noticeable above 1,000 m. If the trousers

are inflated while in flight, the opposite effect occurs during descent of the aircraft: the PASG becomes flaccid and therefore less effective than expected. Careful attention must be paid to changes

in altitude to avoid mishaps en route. Experiments

in a decompression chamber confirmed the theoretical consideration that there will be considerable

increase in the volume of air in the splint as ambient

pressure falls: measurements indicate a change in

volume of almost 50% for every 1,000 ft, or about

16% per 100 m in altitude (—CABMcL, personal

observation). In other words, the contained volume

doubles for every 610 m increase in altitude. This

finding is of importance in helicopter transfers,

where air splints are used frequently.
773

Military Medical Evacuation

The vacuum stretcher consists of a mattress containing a vast number of polystyrene beads. In its

softened state, it is molded around the casualty,

giving support and a degree of comfort. As the air

is extracted from the mattress, the beads expand so

that the mattress makes a total-body splint. However, as the ambient pressure falls, support decreases, requiring the further evacuation of air to

maintain the support. During the descent, the support pressure increases and it is essential to maintain close control of the mattress’s rigidity.

Oxygenation

While changes in air pressure are critical, given

their potential for causing complications, of even

greater importance is the need to deliver an adequate amount of oxygen not only to the patient but

to the flight crew as well. The degree of hypoxia

depends on the partial pressure of oxygen (PO2) in

the atmosphere. The PO2 decreases in direct proportion to the decrease in pressure because the

concentration of atmospheric oxygen remains about

21%. Therefore, at sea level, with barometric pressure approximately 760 mm Hg, the PO2 in dry air is

169 mm Hg (21% of 760 mm Hg). At 3,000 m, where

the barometric pressure is about 500 mm Hg, the

partial pressure is 105 mm Hg (21% of 500 mm Hg).

At the summit of Mount Everest (8,848 m or 29,028

ft, which is slightly below the normal cruising altitude of modern jet transports), the measured barometric pressure is 253 mm Hg and the estimated PO2

is 53 mm Hg. Owing to the presence of water vapor in

the lung and depending on the respiratory rate, the

partial pressure of alveolar oxygen (PAO2) will be

lower to a variable extent. The measured PAO2 on the

summit of Mount Everest is 35 mm Hg, from which

an arterial PO2 (PaO2) of only 28 mm Hg can be

calculated.28

A simple consideration of the effect of barometric pressure on PO2 explains why signs of hypoxia

become increasingly obvious in even healthy persons as they fly higher than 3,000 m without supplemental oxygen. As PO2 falls, the amount of oxygen

transported by hemoglobin also falls, but the reduction is not a linear function of PaO2 because the

shape of the oxyhemoglobin dissociation curve is

sigmoidal (see Figure 25-2 in Chapter 25, Acute

Respiratory Failure and Ventilatory Management).

At sea level, the PAO2 is 100 mm Hg, which results in

an arterial oxygen saturation of 95%. As a person

goes to higher altitude, the PO2 in the surrounding

air decreases, resulting in a decrease in the amount

of transported oxygen. The PO2 in blood in the

lungs and arteries decreases to the point that at

3,000 m, the PaO2 is about 60 mm Hg and the hemoglobin in the arteries is only about 87% saturated

(Figure 27-15). Because of the sigmoid shape of the

oxyhemoglobin dissociation curve, a further increase in altitude results in a precipitous fall in

oxygen saturation, such that at an altitude corresponding to the summit of Mount Everest, the estimated arterial oxygen saturation is only about 50%—

substantially below the normal oxygen saturation

of venous blood at sea level.

The importance of understanding the physics

and physiology of hypoxia and oxygen delivery

stems from the fact that battlefield casualties may

have impaired pulmonary compliance, hypovolemia, anemia secondary to acute blood loss, acidosis, and also be hypothermic—factors that impair

oxygen pickup in the lungs and oxygen delivery at

the cellular level. Studies carried out early in the

Vietnam War heightened concern about arterial

desaturation occurring during high-altitude

aeromedical evacuation. It was not unusual to find

casualties being prepared for aeromedical evacuation with an arterial PO2 of 50 mm Hg or less,

breathing room air with a PO2 of 150 mm Hg. Because the PO2 is about 118 mm Hg in the cabin of a

C-141 pressurized to about 2,400 m, a real potential

existed for fatally low arterial oxygen saturations to

develop.29

Accordingly, supplemental oxygen is needed by

many casualties during aeromedical evacuation.

The amount necessary to maintain a PaO2 at 100 mm

Hg is shown in the upper curve in Figure 27-15. In

some cases, the fraction of inspired oxygen (FIO2)

needed is so high that elective intubation with positive pressure ventilation may be necessary to prevent significant desaturation at altitudes higher

than 2,000 m.30 However, because of the logistical

and manpower constraints associated with the

aeromedical evacuation of casualties who need

mechanical ventilation, such casualties should be

evacuated only in very unusual circumstances.

Almost all the oxygen transported by blood is

carried by the hemoglobin in red blood cells; at

sea level, only 0.2 mL of oxygen per 100 mL of blood

is being carried in direct solution in the plasma.

Therefore, the casualty’s hemoglobin concentration

and blood volume become important determinants of

oxygen transport. Severely anemic or hypovolemic

casualties are at risk during aeromedical evacuation

even if their arterial oxygen saturation exceeds 90%.

Hemoglobin levels should be measured prior to

transfer in casualties who had sustained acute blood

loss; the lowest acceptable level is approximately
Anesthesia and Perioperative Care of the Combat Casualty

774Arterial Oxygen Saturation (%)

2,000 4,000

8,000 10,000 12,000 Altitude (m) 14,000

Fig. 27-15. Maintenance of arterial

PO2 with supplemental oxygen.

7.5 g of hemoglobin per deciliter of blood. A level

of 10 g/dL will have already set into motion the

several physiological compensatory mechanisms

and so the casualty will be able to tolerate air transport.31

Blood volume cannot be so easily checked but is

an equally important determinant of oxygen transport. A study carried out on casualties waiting to be

evacuated from Vietnam found that 13 of 43 were

hypovolemic, and an additional 8 were hypervolemic. Hematocrit values were not useful indicators of volume status, although anemic casualties

were usually hypovolemic. Hypovolemia was especially common in casualties who were evacuated

within 2 to 3 days of being wounded.29

Gravitational and Accelerative Forces

While not commonly thought of as causing patient problems, the effects of gravitational forces (g)

can be quite detrimental during aeromedical evacuation. An individual sitting in a seat has a force

equal to his weight, which is pressing against the

seat. The intensity of this force, equal to the pull of

gravity at the surface of Earth, is said to be 1g. The

factors influencing gravitational forces are weight

and its distribution; gravitational pull; and acceleration, which is caused by the movement of the

vehicle. The most important effect of acceleration is

on the circulatory system because blood, being

mobile, can be translocated from one part of the

body to another. Other tissues can also be displaced

and distorted by accelerative forces, but they usually remain functional.

Both positive and negative gravitational forces

affect casualties on medical evacuation flights. At

accelerations greater than 4g, the systemic arterial

pressure at the level of the heart falls to approximately 40 mm Hg. Therefore, a decrease in cardiac

output may occur, which is secondary to venous

pooling of blood in the lower extremities. Because

of this complication, patients with compromised

cardiac function should be positioned with the head

toward the rear of the aircraft.32

The contrary process is also possible, because

negative gravitational forces can cause a tremendous increase in arterial pressure that, when transmitted to the head, can cause blood pressure to rise

as high as 400 mm Hg. This extreme pressure

increase may cause a paradoxical effect via the

baroreceptor reflex, with slowing and even stopping of the heart. The cerebrospinal fluid in the

cranial vault may act as a buffer to the expansion of

the intravascular blood volume. However, some

small vessels on the surface may rupture and subarachnoid hemorrhages have developed in animals

exposed to negative gravitational forces. For these

reasons, a casualty with a head injury or increased

intracranial pressure should be positioned with his

head toward the front of the aircraft.33

Thermal Stress

Battlefield casualties may have been exposed to

the elements for extended periods. Extremes of

heat and cold can both cause medical problems.

The vascular system’s compensatory vasoconstriction and vasodilation associated with thermal regu100

80

90

70

60

50

40

30

20

10

0

Breathing Oxygen

Breathing Air

6,000

0
775

Military Medical Evacuation

lation may cause significant fluid shifts and thereby

make more difficult the assessment of the adequacy

of volume restoration. The volume-depleted hypothermic patient, whose hemodynamics may be fairly

normal while the vascular bed is contracted, becomes hypotensive as the vascular bed dilates in

response to warmth.

The temperature at Earth’s surface is approximately 20°C; the temperature at 10,000 ft is 0°C.

While most rotor-wing flights are at a lower altitude

than 10,000 ft, the thermal losses to radiation, evaporation, conduction, and convection may be significant and underestimated. Attempts to provide at

least a physiologically normal temperature will

decrease oxygen consumption and improve the

medical officer’s ability to assess the patient.

Noise and Vibration

Rotor-wing aircraft and ground ambulances

create a significant amount of noise and vibration

that are difficult to moderate. These factors may

affect electrocardiographic monitoring, noninvasive blood pressure monitoring, pulse oximetry, and

the auscultatory efforts of the monitoring team.

Because of these limitations, the medical officer

must be able to perform some form of adaptive

monitoring procedure. These include palpating

and assessing radial, brachial, and femoral pulses,

and correlating them to mean arterial pressure;

observing respiratory excursion and patterns of

breathing for any acute changes in status; and intervening appropriately. The simplicity and reliability of mechanical monitors will commonly be lost

during transport. The noise levels, especially in

tracked vehicles and at aircraft takeoff and landing,

are a potent source of stress. Taking clinical measurements on unconscious patients may cause sharp

rises in pulse, blood pressure, and respiration rate if

protective earplugs are not used. The noise levels,

especially when associated with vibrational frequencies above 10 Hz, are more detrimental to

patient care than are the physiological effects of the

vibration.

The speed of transit can also affect the low-frequency vibrations to which casualties can be subjected. In a study of four different types of ground

ambulances, marked increases in two low-frequency

areas (at 4–8 Hz and 16–28 Hz) occurred when the

ambulances traveled between 30 and 45 mph. The

tests were repeated in ambulances fitted with a

“floating” stretcher. The results confirmed that the

vibrations can be damped down in the specific

frequency areas, but the cost of fitting this type of

stretcher would be prohibitive.32

Fatigue and Sleep Lag

The evacuation of patients over many thousands

of miles, through several time zones and different

ambient temperatures, gives rise to general fatigue,

due largely to disturbances of the circadian rhythms

(ie, jet lag).34 In addition, even in a fit person, the

long flight at reduced barometric pressure, with the

resulting lowered oxygen tensions, gives rise to

serious fatigue problems. The level of degradation

of performance is difficult to quantify, but experimental work in a decompression chamber showed a

marked reduction in the appreciation and performance of tests when initially attempted, although

once learned, there were no problems with retention of the newly acquired skills.35 A general level

of fatigue is demonstrated by patients during longdistance transfer flights, especially when overnight

stops are necessary. The marked improvement as a

result of direct flights was first noted in the German

sick and wounded who were being evacuated during the Spanish Civil War: even though the aircraft

were unpressurized and unheated, nonstop flights

were considered better for the patients.25

Workers in New Zealand have a possible treatment for jet lag. The pineal gland (ie, the “third”

eye) secretes melatonin, which is considered to be

one of the principal factors in setting the biological

clock. Preliminary findings indicate that when research subjects take formulations of melatonin, compared with a placebo, the effects of jet lag are markedly reduced.36

MEDICAL DETERMINANTS OF SAFE EVACUATION

Specific medical factors, such as abdominal and

eye injuries, may increase the risk of medical evacuation. Clearly, other factors (eg, enemy action and

mechanical problems associated with the design

and operation of the aircraft) may adversely affect

the evacuee, but they will not be discussed here.

In-Flight Medical Problems of Long-Range

Aeromedical Evacuation

Only limited historical data have been gathered

on the medical aspects of aeromedical evacuation.

The most useful data are from the Vietnam War;
Anesthesia and Perioperative Care of the Combat Casualty

776

although long-range casualty evacuation occurred

during both Operation Just Cause in Panama (1989)

and the Persian Gulf War (1990–1991), the number

of American casualties was too small to draw meaningful conclusions, although much interesting anecdotal information was collected.

The Vietnam War

The low frequency of death observed during

aeromedical evacuation (< 1 per 20,000 casualties

evacuated) during the Vietnam War does not necessarily mean that nonlethal medical problems were

similarly infrequent. In lieu of data from a more

recent war, the U.S. Air Force medical evacuation

experience in the early years of the Vietnam War,

in which casualties were evacuated through

an aeromedical staging facility in the Philippine

Islands prior to being evacuated to Japan, is of

interest. Of some 20,000 casualties already in the

evacuation chain, many (68 of 128 in one check)

were found to have developed signs and symptoms indicative of the possible development of

potentially serious complications. Complications

were especially common in three categories of

casualties29(p276):

1. Vascular injuries. Of 347 casualties who

had vascular reconstruction, 187 were

found during aeromedical evacuation to

have developed signs and symptoms suggestive of a complication (ie, a cool,

pulseless extremity; excessive pain in the

limb; excessive drainage; fever). No fewer

than 57 of the 187 (approximately 30%)

required an extremity amputation.

2. Chest injuries. Of 629 casualties who had

chest trauma, 137 were found to have a

pneumothorax or a hemothorax. One third

of this group, 46 casualties, presented with

respiratory distress, and 16 of 17 in whom

arterial blood-gas measurements were

made had a PaO2 less than 80 mm Hg while

breathing room air. It seems likely that

these casualties had pathologically low arterial oxygen saturation during evacuation.

Thirty-one casualties of the group of 137

had a nonfunctioning chest tube in place.

Heimlich valves had been used in some

patients and in several this was defective,

allowing air to remain in the pleural space.

3. Abdominal injuries. Of 626 casualties with

abdominal trauma, 117 had signs and symptoms during the evacuation that indicated

the need for reoperation. Among the more

common indications were dehiscence, evidence of peritonitis, intestinal obstruction,

stress ulcer hemorrhage, hemorrhage from

an abdominal wound, and wound sepsis.

It should be understood that (a) these complications were apparent after 6-hour evacuation flights,

(b) many of the complications had probably existed

prior to evacuation but had not been diagnosed,

and (c) these casualties probably were evacuated

prematurely. The Vietnam aeromedical evacuation

experience strongly suggests that the medical problems that do develop are much more likely to be

associated with the original injury than with abnormal environment in the evacuation.

Operation Just Cause and the Persian Gulf War

The distinguishing military medical characteristics of Operation Just Cause in Panama was the

paucity of third-echelon medical assets deployed

with the combat units. Although a surgical team

was present to perform emergency lifesaving surgery on the critically wounded, initial surgery

was performed on most casualties in military hospitals in San Antonio, Texas. After receiving first aid

at the unit level and MASF, these casualties, together with those who had already been operated

on, were evacuated in C-141s, which soon became

aerial emergency and intensive care wards. Not

surprisingly, “In-flight care for these fresh combat

casualties was a challenge for the usual crew of two

flight nurses and three aeromedical evacuation

technicians.”37(p943)

In contrast to Operation Just Cause, the Persian

Gulf War was characterized by a long buildup period during which extensive third-echelon medical

assets were deployed. Even so, the anticipated

casualty rates were so high that the need to evacuate

fresh, unstable casualties was thought to be highly

likely. As a result of the Panama experience and

breaking with the tradition existing since World

War II, medical commanders decided to assign physicians to at least some tactical and strategic air

evacuation flights so as to optimize the success of

lifesaving, in-flight, medical interventions.37 Fortunately, actual U.S. and Allied casualties were only a

tiny fraction of those anticipated, and the need for

lifesaving interventions was correspondingly small.

The experiences in both of these wars suggest

that injury-related complications, rather than the

adverse physiological conditions of the evacuation

environment, will be the major source of problems.
777

Military Medical Evacuation

Furthermore, it seems likely that the proportion of

evacuated casualties who develop injury-related

complications during evacuation will be inversely

related to the interval between wounding and evacuation (ie, the more quickly the casualty is evacuated

after wounding, the more likely it is that a complication will develop). Therefore, both during mass

casualty situations and when the theater evacuation policy is very short (eg, during a short but

intense conflict), military anesthesia providers

should be especially alert to the possibility of inflight medical problems.

Civilian Experience

A relevant civilian experience also supports the

view that medical problems during evacuation are

more likely to be due to the original injury than due

to evacuation per se. After resuscitative surgery

(usually a laparotomy) was carried out in a rural

hospital, patients were transferred to a regional

trauma center within 48 hours of injury. No deaths

occurred during evacuation, but 8 of the 19 patients

studied developed tachycardia or became hypotensive; 7 of the 8 unstable patients subsequently

died. Transport time averaged 2.4 hours. All but 3

of the patients had blunt trauma as the mechanism

of their injuries. A physician and a nurse accompanied all patients, all received intravenous fluids,

and all but 2 were mechanically ventilated.38

Patient Conditions Leading to Medical Instability

The major constraints placed on battlefield evacuation from and to the first and second echelons of

care arise not so much from the conditions of the

casualties but from enemy action and the availability of the means of evacuation. Evacuation from

higher echelons may, however, be constrained by

the aeromedical evacuation policy of the U.S. Air

Force, which is based on the realization that some

patients’ medical conditions predispose to in-flight

complications. The air force does not recognize any

absolute contraindication to aeromedical evacuation, but a variety of conditions either constitute

relative contraindications to evacuation or require

that arrangements be made for specialized treatment if evacuation is to proceed.2(pE-3),31

When they enter the U.S. Air Force medical evacuation system, casualties should be stable enough to

tolerate a 1- to 24-hour trip with a high probability

that complications will not occur. The necessary

degree of stabilization depends on the operational

situation: tactical missions are typically shorter than

strategic missions. Therefore, less-stable patients

might tolerate tactical evacuation, but strategic

evacuation might be highly detrimental.

Abdominal Injuries

Patients with abdominal injuries should be carefully evaluated by a general surgeon prior to flight.

Use of nasogastric or rectal tubes or both should

be considered to avoid both the distention frequently encountered with a nonfunctioning bowel and

the gas-volume changes associated with varying

barometric pressure. Extra colostomy bags should

accompany the patient. Drainage is more profuse

at altitude because of gas expansion. It is essential that military surgeons close all abdominal incisions with retention sutures to minimize in-flight

dehiscence due to expansion of intraabdominal

gas.

Cardiovascular Disease

Patients with severe cardiovascular disease usually have reduced tolerance to hypoxia, but they

generally do well during flight if provided supplemental oxygen. With appropriate preparation monitoring, patients with recent myocardial infarctions

can usually be moved by airlift. Unstable patients

requiring in-flight cardiac monitoring will be moved

with a medical attendant, and the referring medical

treatment facility must provide an air force–approved monitor. Patients who have had a myocardial infarction should not be evacuated for at least

10 days, and should have been free of pain for 5

days. If monitored, such patients must be accompanied by a physician.

Thoracic Injuries

Chest tubes should be left in place in casualties

with thoracic injuries. However, each chest tube

will require a Heimlich valve and an underwater

chest drainage system approved for air evacuation

use. Ideally, patients with recently removed chest

tubes should not be airlifted until the following

conditions are met:

• at least 24 hours have elapsed since the

chest tube was removed;

• normal expiratory and lordotic chest radiographs have been taken at least 24 hours

after removal of the chest tube (just prior to

airlift, if possible), with an interpretation in

the patient’s medical record; and
Anesthesia and Perioperative Care of the Combat Casualty

778

• an occlusive dressing has been placed at

the site where the chest tube was removed.

Eye Injuries

Penetrating eye wounds or surgery or both can

sometimes introduce air into the globe of the eye,

making it susceptible to the effects of oxygen

deficiency and, especially, decreased barometric

pressure. Presence of gas in the posterior chamber

comes as close to constituting an absolute contraindication to high-altitude aeromedical evacuation

as there is likely to be. A delay in evacuation, or an

altitude restriction, is recommended for such patients.

Hematological Considerations

Ideally, patients should have a preflight hemoglobin concentration of 10 g/dL or a hematocrit of

0.30. Severely traumatized patients may have readings below those levels, and supplemental oxygen

may be required. Hemoglobin concentration can be

as low as 8.5 g/dL if the patient’s condition is

chronic, stable, and not due to bleeding.

Infectious Disease

Patients in the infectious stage of a serious communicable disease need to be segregated from the

other evacuees.

Maxillofacial Injuries

Due to the increased potential for nausea and

vomiting, patients with wired, immobilized upper

and lower jaws must have a quick-release mechanism applied or have easy access to wire cutters in

their possession. Premedication with an antiemetic

should be considered.

Neurological Injuries

The decreased PO2 at altitude can cause increased

intracranial pressure in casualties with head injuries. Low-flow oxygen and an altitude restriction

should be considered for flight. Noise, vibration,

and thermal stresses can precipitate seizures, and

adequate antiseizure medication levels should be

established before flight. Valsalva’s maneuver

should be avoided by patients at risk from increased intracranial pressure. Therefore, administrating

a preflight decongestant and inserting a polyethylene tube into the patient’s middle ears should be

considered, especially if the patient is comatose.

Patients who have had a craniotomy should not be

evacuated for at least 48 hours after surgery, and

should be awake and alert. The subtle changes in

neurological status that are usually discovered during routine neurological checks are very difficult to

detect during flight; patients requiring close observation are poor candidates for aeromedical evacuation. Stable, comatose patients can be transported.

Decreased humidity at altitude dictates that patients with a loss of corneal blink reflex be provided

with bilateral eye patches and eye ointment or liquid tears. Intraventricular monitoring cannot be

accomplished during flight.

Orthopedic Injuries

Ideally, casts on recent fractures should be at

least 48 hours old. All casts should be bivalved

unless that would jeopardize the stability of the

fracture. Free-swinging weights for traction are

unacceptable for flight. Cervical traction is available via a Collins traction device; however, a medical officer must be present when the device is applied. Patients using crutches should travel by litter

because of the safety factors involved in moving

about on unstable aircraft. Crutches should accompany the patient and be stowed aboard the aircraft.

Thermal Injuries

In general, casualties with thermal injuries should

not be evacuated during the period of fluid sequestration (ie, the first 48 h). Thermal injuries should

be covered with occlusive dressings. Escharotomies

are required for full-thickness circumferential burns.

Extra burn dressings for in-flight reinforcement

should be provided. Limited infusion pumps and

poor in-flight refrigeration capabilities preclude the

use of total parenteral nutrition. Infusions of 10%

dextrose in water with necessary electrolytes should

be ordered as a short-term substitute. Phosphorous

injuries should be covered with saline-soaked dressings. Large vesicles and bullae should be protected

during the evacuation with large, bulky dressings.

Vascular Injuries

Vascular repairs should be clearly recorded on

Patient Evacuation Form DD 602 or 1380. Casts that

are less than 48 hours old should be bivalved and

windowed over the injured area in case excessive

swelling occurs during flight.
779

Military Medical Evacuation

Psychiatric Illness

Severely ill psychiatric patients (Classification

1A) require a litter, leather wrist and ankle restraints, and sedation. Patients whose psychiatric

illnesses are of intermediate severity (Classification 1B) require a litter and sedation, and restraints

must be available. All psychiatric patients on litters

must be searched, and all sharp objects such as

razor blades and pocket knives must be removed as

part of the antihijacking procedure. A secondary

search must be accomplished just before enplaning.

Drug and Alcohol Abuse

Soldiers who are being treated for drug and alcohol abuse should undergo 3 to 5 days of detoxification before they are airlifted. An aeromedical evacuation mission is not equipped to deal with acute

withdrawal symptoms.

Preparation for Evacuation

Initial Assessment

The Advanced Trauma Life Support (ATLS)

course of the American College of Surgeons is taught

to military physicians as part of the Combat Casualty Care Course.39 Prior to evacuation, the initial

assessment of the casualty’s condition is based on

the ATLS ABCs (airway, breathing, and circulation)

and the extent and location of injury, especially

when the time available for battlefield medical

implementation of ATLS is short and injuries may

have been missed.

The “Golden Hour” concept, which arises from

the civilian trauma experience, suggests that if a

trauma patient with a survivable injury who is in

clinical shock does not receive the definitive care

necessary to reverse the process within the first

hour after entering the shock state, the long-term

survivability drops below 10%. This is independent

of the quality of care after that 60-minute period.30

In the context of combat casualty care, providing

care within the Golden Hour is important, because

about 90% of the total combat mortality occurs

within the first hour after wounding (see Chapter 1,

Combat Trauma Overview, for a more complete

discussion). In Vietnam, transport took 35 minutes

after the patient was loaded.40 The Germans41 and

Swiss42 can transport at least 90% of their population in 15 minutes or less, but of course conditions

for civilian aeromedical evacuation in these countries are more favorable than they were in Vietnam:

there is no need to pick up casualties from a dense

jungle or from a landing zone exposed to enemy

small-arms fire.

The chaos of the battlefield or aid station may

preclude an organized approach to each casualty.

However, the rules of assessment, resuscitation,

and stabilization must be followed in an orderly

manner. This provides as safe a mechanism as

possible for the transport of the trauma patient.

Supplies and Equipment Required From the

Originating Medical Treatment Facility

The MASF does not have any equipment that can

be given in replacement: all equipment and supplies that each casualty will need during the entire

evacuation process must be supplied by the originating medical treatment facility (MTF) and accompany the casualty to the aeromedical staging facility. U.S. Army anesthesiologists should be aware of

the following U.S. Air Force requirements for supplies and equipment31:

• Patient medications. Patients transported

intratheater should be given a 3-day supply

of medications and supplies; intertheater

patients should be given a 5-day supply.

• Intravenous fluids. The referring MTF

should provide a 3-day supply of intravenous fluids and infusion equipment, including all necessary supplies for antibiotic administration, if required.

• Special medical equipment. Special equipment includes cardiac monitors, ventilators,

Stryker frames, continuous-suction units, pulse

oximeters, oxygen analyzers, and restraints.

As a rule, dressings will be reinforced but not

changed during flight due to the relatively unclean

in-flight environment. Serious complications such

as bleeding, increased pain, or swelling may require wound inspection. Routine dressings will be

provided by the air evacuation crew; however,

unique dressings or dressings for patients with

excessively draining wounds should be provided

by the originating MTF.

Physician’s Orders

Although the recommendation has been made

that flight surgeons augment the basic air evacuation crew on selected tactical and strategic evacuation missions,37 the absence of physicians on most

U.S. Air Force aeromedical evacuation missions
Anesthesia and Perioperative Care of the Combat Casualty

780

emphasizes the absolute criticality that clear and

concise orders, covering the entire patient transfer,

be written on the Patient Evacuation Tag, DD Form

602. The referring physician is legally responsible

for all medical care until the patient reaches the

destination facility.

Stretchers and Securing the Casualty in the

Aircraft

The first principle of aeromedical evacuation is

that the casualty must be securely fastened to the

evacuation platform. If a casualty has an extremity

fracture, the fracture must be immobilized for both

safe and humane transportation. This is especially

necessary when bumpy ground evacuation is expected.

At this time, there are at least 30 different types of

stretchers available for use by NATO forces, constructed from various materials, but still based on

the Swiss designs of 1912 and 1922. This multiplicity of stretchers can lead to problems in locating the

stretcher in the different types of transport. With

the wealth of new materials available at the end of

the 20th century, it seems remarkable that a suitable

stretcher has not been developed that is compatible

with the road, rail, sea, and air requirements. In a

mass casualty situation, the loading of stretcher

patients is important: more seriously ill casualties

must be positioned to ensure all-around access for

the medical and nursing team. Also, adequate facilities must be available at the departure airhead to

enable rapid loading of the casualties. It is also

necessary to have the ground facilities to maintain

full medical care for at least 24 hours, should there

be a delay in the evacuating flights.

The differing aircraft likely to be used have loading doors at varying heights above ground. Some,

like the C-130 Hercules and the C-141 Starlifter, can

of course be loaded directly, but when commercial

jets such as the VC-10, Lockheed 1001, and Boeing

737, 747, and 767 are used in medical evacuation,

special loading ramps are necessary.

In all forms of transportation, but especially by

air, it is essential to ensure that the patients are

securely strapped to their stretchers,. These, in

turn, are located on the fixed stretcher supports to

minimize the acceleration and deceleration forces

that are generated during ground transportation

and takeoff and landing of fixed-wing aircraft.

Stretchers are traditionally placed longitudinally,

with the casualty traveling head first, whatever

form of transport is being employed. Many have

suggested that the ideal siting of stretchers would

be transverse: across the aircraft cabin. This siting

would lessen the fore-and-aft movements of body

fluids during the acceleration and deceleration

phases of travel.

Stryker frames are generally indicated for

paraplegia, quadriplegia, cervical fractures, severe

burns, and those patients requiring total assistance.

Patients with cervical injuries and wearing halo

traction may be transported on a regular litter or, if

stabilized, they may be transported as ambulatory

patients. All components of the Stryker frame must

be sent with the casualty from the originating MTF

to allow continuity of patient care and turning of

patients throughout transfer. Stretcher frames and

the stretcher harness must be stressed to at least 6g

to give a wide margin of safety should it be necessary to abandon the takeoff in a fixed-wing aircraft.

Catheters

Intravenous Infusions. The military anesthesiologist must be extremely attentive to the establishment, securing, and maintenance of intravenous

lines. These lines are important for the continued

resuscitation of the casualty as well as for the administration of needed pain medication and other

drugs. The establishment of large, easily accessible,

secure lines should be uppermost in the anesthesiologist’s mind, as these lines may provide the only

means of drug delivery.

Patients who require intravenous fluids on the

ground will also require them during the flight,

owing to the excessively dry cabin environment.

Catheter function should be assessed prior to transport to ensure that the catheter is securely in place.

Patients requiring antibiotics without fluid replacements should be switched to a heparin lock with

heparin flushes provided. A 3-day supply of intravenous fluid should accompany each patient who

requires intravenous fluids.

Urinary Catheters. Indwelling urinary catheters

and drainage bags in use before transport should be

left in place during evacuation, or inserted before

the flight if urinary retention is a problem. The

internal balloon should be filled with sterile, normal saline or water instead of air to avoid gas

expansion during the flight.

Nasogastric Tubes. Nasogastric tube insertion is

recommended for patients with abdominal wounds,

abscesses or obstructions, paraplegia or quadriplegia, or the potential for paralytic ileus. Limited

suction capabilities are available aboard the aircraft; however, the distal end of the tube may be left

to drain by gravity into a glove or bag.
781

Military Medical Evacuation

Respiratory Support

The utmost concern in the mind of every anesthesiologist is the adequacy of the patient’s airway

and therefore of the patient’s ventiIation. The need

to establish a definitive airway rapidly is foremost

in ATLS instruction. Several aspects of the maintenance of a patent airway during aeromedical evacuation deserve special mention.

Airway Management. Endotracheal tubes should

be used if the patient requires assisted ventilation

and should be inserted before aeromedical evacuation begins. Balloon cuffs should be filled with

normal saline instead of air, as gas expansion at

altitude may cause tracheal damage.

Airway Stability. Several questions must be

answered while the casualty is being prepared for

evacuation. Is the patient breathing spontaneously?

Will the patient’s airway need attention? What is

the potential that the patient’s airway will be compromised? The significance of the airway in air

ambulance transport revolves around the ability to

control ventilation and the need for personnel

(nurses, medics, respiratory technicians) and equipment to aid that ventilation. Coexisting injuries

may compromise the airway, such as cervical instability and severe facial trauma including LeFort

fractures. The military anesthesiologist must remember that airway problems are especially common in casualties with burn injuries.

Tracheostomies. Tracheotomy tubes should be

changed before flight and an extra tube should be

sent with the patient.

Ventilators. Ventilator-dependent patients will

be accompanied by a respiratory therapist or other

appropriate medical attendant from the referring

MTF. The apneic patient requires full ventilatory

support from a respirator that will provide automatic control. There are many such machines available, but in the context of military aeromedical

evacuation, it is likely that compactness and durability will be preferred to sophistication (ie, a multitude of dials and controls, such as those seen in

intensive care units). A further constraint is the

mode of operation. All but the simplest ventilators

require a compressor to provide the gas that drives

the ventilator. Transportation ventilators must be

lightweight, rugged, durable, and simple to operate. Manual ventilation may be all that is available

on a helicopter flight.

Humidifiers. Because the ambient cabin humidity during long-distance aeromedical evacuation is

usually between 5% and 20%, marked insensible

water loss and drying of the respiratory tract should

be expected. This consideration applies to all patients but especially to those in whom the normal

humidifying function of the nose is prevented, such

as casualties with a tracheostomy or an endotracheal tube. It will therefore be necessary to provide

adequate humidification to avoid the problems of

ventilating with dry gases.

There are many humidifiers, as there are ventilators, but the simplest, and therefore the most appropriate, device is the small condenser humidifier,

which can be plugged into the ventilating circuit. A

lightweight item, it works by passing the fresh

gases through the condenser foil on which the water

vapor in the expired air condenses. The water is

then available to humidify the inspired oxygen. A

bonus, of course, is the degree of heat conservation

achieved during the respiratory cycle. The efficiency of the “Swedish nose”(the Humid-Vent HeatMoisture Exchanger, manufactured by Gibeck Respiration Co., Uplands, Väsby, Sweden) is such that

a relative humidity of approximately 50% can be

maintained during the transfer.43

Oxygen. There are many simple devices available to deliver oxygen, ranging from nasal cannulae

and the simple mask, which deliver variable concentrations and flows of oxygen, to fixed-dilution

Venturi masks, which are capable of delivering 24%

to 50% oxygen. It is difficult to tap into the main

aircraft oxygen supplies, so the source of oxygen for

patients must be cylinders; however, when required

in large numbers, oxygen cylinders produce a severe weight penalty. A further problem is the availability of adequate numbers of the appropriate cylinder sizes. It is therefore necessary to consider

alternative sources of oxygen for in-flight use.

Liquid oxygen, despite being considered in some

quarters to be dangerous cargo on aircraft, offers an

excellent alternative means, as can be seen from the

volumes of gaseous oxygen available from one 30-

L flask of liquid oxygen: one such flask is equivalent

to 18 large cylinders of compressed gas, with the

obvious weight savings. The problem of fitting a

heat exchanger to avoid freezing of the delivery

outlet can be overcome without much difficulty.

The pressure-swing absorber system (ie, the oxygen

concentrator) must also be considered as a source of

additional oxygen. The concentrator works by forcing dried ambient air, at a low pressure, through

fractionating columns of zeolite crystals. As air

passes through the zeolite, all other constituents of

air are removed except oxygen and argon. At the

delivery end of the unit, a mixture of up to 95%

oxygen and 5% argon is obtained, at a rate of 4 L/

min. Of course, this is not the standard required for
Anesthesia and Perioperative Care of the Combat Casualty

782

medical oxygen, but is a perfectly satisfactory oxygen supply. There have been no reports of the

effects of ventilating with a mixture of oxygen and

argon. The oxygen concentrator requires a power

source to drive the compressor and produce a continuous supply of oxygen, but little maintenance. If

the flow through the columns is increased, a higher

volume of oxygen is produced, but the percentage

of oxygen falls in direct relation to the increased

flow through the columns.

Fracture Stabilization

The problems that increasing and decreasing

gravitational forces exert on fractures during aircraft acceleration and deceleration have already

been discussed. It is during the transport of patients with severe fractures that the problems assume great importance.

Most patients transported by air or ground ambulance will be immobilized on stretchers or

gurneys. The ability to maintain in-line traction for

cervical injuries as well as continued support for

long-bone fractures is essential. The goal is to

prevent the conversion of stable injuries to unstable

injuries. It is necessary in all cases of spinal fracture, especially the cervical spine, with or without

paralysis, to ensure that the degree of traction on

the spine is maintained accurately. Although modern jets will be flying above the weather, there is

still the problem of clear-air turbulence. When this

happens, the gravitational forces exerted as the aircraft is bounced about can increase 4- to 5-fold, so

that a traction weight of 10 lb will immediately

increase to 40 or 50 lb, with the obvious deleterious

effects on the patient, even though such forces occur

for extremely short periods of time.

The Stryker frame or its derivatives used for

transferring patients with spinal fractures did not

address the problems of (a) rapid increases in forces

exerted and (b) difficulty in moving the frame and

patient.44 The Povey turning frame addresses many

of the problems experienced with the Stryker frame.45

It weighs only 70 lb and can easily be moved. The

traction weights are maintained horizontally, eliminating the high vertical-acceleration forces. The

weights can also be maintained during any necessary nursing procedure. The Povey frame takes up

much less space on the aircraft, and the amount of

whip during turbulent conditions is much reduced.

The whole frame can be turned through 360°

while head and neck traction are maintained. This

is important for the nursing care of patients with

fracture and paralysis. In the quadriplegic patient,

it is essential to maintain full nursing care to the

skin, which, deprived of sensory input, can rapidly

become broken and develop serious infection at the

damaged area.

Historically, motion sickness does not appear to

have been a significant problem in transporting

physiologically stable casualties. In all cases of

spinal injury it is essential to ensure that a nasogastric

tube is passed prior to takeoff, as one of the immediate and fatal complications of such injuries is

acute dilation of the stomach, leading to massive

emesis. The presence of the tube will permit continuous aspiration of the stomach, thus avoiding

the complication.

Casualty Assessment and Monitoring

Ideally, the same monitoring equipment found

in an intensive care unit in a fourth-echelon hospital

(or a Level-1 trauma hospital) would be available

throughout the evacuation chain. Obviously, however, logistical realities constrain equipment availability. Inspection of the patient is probably still the

best monitor available. As with the ventilators, it is

necessary that all items used must be rugged, lightweight, and compatible with the aircraft type. The

power supplies in aircraft vary so, as the degree of

sophistication of the electronic monitors used increases, it is necessary to know the type of airplane

to be used.

All monitoring equipment generates a degree of

electromagnetic interference, which can interfere

with navigational or communication equipment of

the aircraft. It is therefore necessary for all monitors

to be tested for such interference. Standards have

been formulated, but at this time very few of the

items tested have received a seal of approval on first

testing.46

It would seem logical to employ battery-operated monitoring equipment in an attempt to avoid

electromagnetic induction. There are, however,

problems with the type of battery available during

air transport. The sight of an acid-filled battery

being carried aboard—even the nonspill type—will

raise concerns about safety. The duration of battery

life is also an important consideration as the battery

chargers available for use give rise to an induction

field, which precludes their used in flight. Several

monitoring packages are now being produced that

will, it is hoped, satisfy the safety requirements.
783

Military Medical Evacuation

SUMMARY

The requirement to evacuate the sick and

wounded is of much greater importance in military

medicine than it is in civilian medical practice. This

fact is a consequence of one of the distinguishing characteristics of military medicine: the provision of care by echelons. The nature of evacuation

and the conditions under which it is carried out

differ according to the echelons. At one extreme

is the army’s evacuation from the battlefield of

gravely wounded, unstable combat casualties by

ground ambulance or rotor-wing aircraft. At the

other extreme is the air force’s intertheater (strategic) evacuation of stable combat casualties by longrange jet transport. The medical complications of

evacuation arise primarily from the basic injury,

but aspects of the somewhat unphysiological environment of high-altitude, long-range aeromedical evacuation may contribute to morbidity and

even mortality. Foremost among these are (a) decreased barometric pressure, which can cause expansion of abnormal collections of gas trapped

within the body; and (b) decreased PO2, which may

give rise to arterial desaturation and defective oxygen transport. It is imperative that military anesthesiologists understand how to order and to carry

out evacuation from the battlefield and from the

levels of care in which they ordinarily practice.

Recognizing the capabilities and limitations of the

evacuation assets serving each level of care is especially important.

REFERENCES

1. Pirogov NI. Nacala Obcsej Voenno-Polevoj Chirurigii. (Origins of Military Field Surgery.) St. Petersburg, Russia:

1857. In German: Grundziige der Allgemeinen Kriegscherurgie. Leipzig, Germany: 1864. No English translation is

available.

2. Department of the Army. Medical Evacuation in a Theater of Operations. Washington DC: Headquarters, DA; 31

October 1991. Field Manual 8-10-6.

3. Ransom JE. Care of the sick and wounded in early wars. CIBA Symposium. 1947;8:541–542.

4. Polybius; Scott-Kilvert I, trans. The Rise of the Roman Empire. London, England: Penguin Books; 1979: 477.

5. Uzac M, Suffrin-Herbert M. Neuvieme Question. Paris, France: Premier Congress International de l’Aviation

Sanitaire; 1929.

6. Blanco RL. Wellington’s Surgeon General: Sir James McGrigor. Durham, NC: Duke University Press; 1974: 121.

7. Letterman J. Medical Recollections of the Army of the Potomac. New York, NY: D Appleton and Company; 1866: 171.

8. Meneces ANT. The transport of casualties by air. J Roy Army Med Corps. 1951;96:1–12.

9. Lam DM. To pop a balloon: Aeromedical evacuation in the 1879 siege of Paris. Aviat Space Environ Med.

1988;59:998–991.

10. William AW The flying ambulance. Milit Surg. 1943;92:443–446.

11. McLaren CAB. Aeromedical evacuation. Aviat Med Q. 1987;1:41–49.

12. Scholl MD, Geshekter CL. The Zed Expedition: The world’s first air ambulance? J R Soc Med. 1989;82:679.

13. Kowalzig H. Long distance transportation of the wounded at high altitudes. Deut Militarzt. 1940;5:10–14.

14. Schmidt F. Transport of the wounded by plane. Deut Militarzt. 1940;5:7–10.
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784

15. Cosmas GA, Cowdrey AE. Medical Service in the European Theater of Operations. Washington, DC: Center of

Military History, US Army; 1992: 106.

16. Futrell RF. Development of aeromedical evacuation in the USAF: 1909–1960. USAF Historical Division, Air

University. 1960: 507. Cited in: Mabry EW, Munson RA, Richardson LA. The wartime need for aeromedical

evacuation physicians: The U.S. Air Force experience during Operation Desert Storm. Aviation, Space, and

Environmental Medicine. 1993;Oct:941–946.

17. Marsh AR. A short but distant war. J R Soc Med. 1983;76:972–982.

18. Dorland P, Nanney J. Dust Off: Army Aeromedical Evacuation in Vietnam. Washington, DC: Center of Military

History, US Army; 1984: 9.

19. Champion HR, Sacco WJ, Carnazzo AJ, Copes W, Foulty W. Trauma score. Crit Care Med. 1981;9:673–676.

20. Clemmer TP, Orme JF, Thomas F, Brooks KA. Prospective evaluation of the CRAMS scale for triaging major

trauma. J Trauma. 1985;25:188–191.

21. Champion HR. Helicopter triage. Emerg Care Q. 1986;2:13–21.

22. Association of Air Medical Services. Position paper on the appropriate use of emergency air medical services.

J Air Med Transport. Sept 1990;29–33.

23. Medical News and Perspectives. JAMA. 1994;271(16):1225–1228.

24. US Departments of the Army and the Air Force. Worldwide Aeromedical Evacuation. Washington, DC: HQ DA,

DAF; 1979. Air Force Regulation 164-5, Army Regulation 40-535.

25. Parson CJ, Bobechko. Aeromedical transport: Its hidden problems. Can Med Assoc J. 1982;126: 237–243.

26. Dolev E. Early evacuation of patients from the battlefield after laparotomy: Experience in Vietnam, Israel and

the Falklands. Milit Med. 1987;152: 57–59.

27. Loder RE. Use of hyperbaric oxygen in paralytic ileus. Br Med J. 1977;1(6074):1448–1449.

28. West JB. Everest: The Testing Place. New York, NY: McGraw-Hill Book Company; 1985.

29. Whelan TJ, Burkhalter WE, Gomez A. Management of war wounds. Curr Probl Surg. 1967;Sept:339.

30. Stene JL, Grande CM. Trauma Anesthesia. Baltimore, Md: Williams & Wilkins; 1991: Chap 15.

31. Department of the Air Force. Physicians’ Roles and Responsibilities in Aeromedical Evacuation. Washington, DC:

Secretary of the USAF; 1995: in press. Air Force Joint Manual 41-306.

32. Snook R, Pacifico R. Ambulance ride: Fixed or floating stretcher. Br Med J. 1976;2:405–407.

33. Hippke E. Transport of the sick and wounded. Milit Surg. 1940;86:439–440.

34. Siegel PV. Time zone effects. Science. 1969;164:1249–1255.

35. Denison DM, Ledwith F, Poulton EC. Complex reaction times at simulated cabin altitudes of 5,000 feet and 8,000

feet. Aerospace Med. 1966;37:1010–1013.

36. Petrie K, Conaglen JV, Thompson C, Chamberlain K. Effect of melatonin on jet lag after long haul flights. Br Med

J. 1989;298:745–747.
785

Military Medical Evacuation

37. Mabry EW, Munson RA, Richardson LA. The wartime need for aeromedical evacuation physicians: The US Air

Force experience during Operation Desert Storm. Aviation, Space, and Environmental Medicine. 1993;Oct:941–946.

38. SR Sharar, GK Luna, Rice CL, Valenzuela TD, Copass MK. Air transport following surgical stabilization: An

extension of regionalized trauma care. J Trauma. 1988;28:794–797.

39. Committee on Trauma, American College of Surgeons. Advanced Trauma Life Support Program for Physicians:

Instructor Manual. 5th ed. Chicago, Ill: American College of Surgeons; 1993.

40. Neel S. Army aeromedical evacuation procedures in Vietnam. JAMA. 1968;204:99–103.

41. Burghart H. Helicopter rescue for traffic accidents: The West German experience. Emerg Med Serv. 1986;June:72–74.

42. Brismar B, Dahlgren BE, Larsson J. Ambulance utilization in Sweden: Analysis of emergency ambulance

missions in urban and rural areas. Ann Emerg Med. 1984;13:1037–1039.

43. Mapleson WW. Assessment of the condenser humidifier. Br Med J. 1963;1:300–305.

44. Stryker H. A device for turning the frame patient. JAMA. 1939;113:1731–1732.

45. Povey RW. New turning-frame. Br Med J. 1968;2:114.

46. Nish WW, Walsh FW, Land P, Swedenburg M. Effect of electromagnetic interference by neonatal transport

equipment on aircraft operation. Aviat Space Environ Med. 1989;60:599–600.
Systemic Hypothermia

787

T. CAMERON MACCAUGHELTY, M.D.*; BRIAN G. MCALARY, M.D.†; AND MICHAEL MOON, M.D.‡

Chapter 28

SYSTEMIC HYPOTHERMIA

INTRODUCTION

NORMAL THERMOREGULATION

Temperature Measurement

Neural Temperature Control

Heat Production

Heat Loss

Heat Conservation

DEFINITION AND CLASSIFICATION OF HYPOTHERMIA

CLINICAL AND LABORATORY MANIFESTATIONS

Organ-System Effects

Blood Chemistry Abnormalities

CLINICAL PREVENTION AND TREATMENT

Supplemental Warming Devices

Blood and Fluid Warmers

Treatment in the Postanesthesia Care Unit

CARDIOPULMONARY RESUSCITATION

OTHER CONCERNS OF SPECIAL INTEREST

SUMMARY

*Formerly, Lieutenant Colonel, Medical Corps, U.S. Army Reserve; Group Surgeon, 11th Special Forces Group (Airborne), U.S. Army First

Special Forces; Commanding Officer, 306th U.S. Army Reserve Field Hospital; currently, Chief of Anesthesiology, Illinois Valley Community

Hospital, 925 West Street, Peru, Illinois 61354

†Formerly, Commander, Medical Corps, U.S. Navy; Director of Medical Corps Programs, Health Sciences Education and Training Command,

National Naval Medical Center, Bethesda, Maryland; and Chairman, Department of Anesthesiology, National Naval Medical Center, Bethesda,

Maryland 20889-5600; currently, Lecturer and Consultant in Anesthesia and Critical Care, 9260 Broken Timber Way, Columbia, Maryland

20145

‡Colonel, Medical Corps, U.S. Army; Staff Anesthesiologist, Madigan Army Medical Center, Fort Lewis, Washington 94831-5000
Anesthesia and Perioperative Care of the Combat Casualty

788

INTRODUCTION

Military operations in cold environments have

the potential to create vast problems for military

medical services. Everything is more difficult to do.

Evacuation of casualties is impeded. Infectious diseases are much more common. And cold by itself

becomes an agent of injury, as was pointed out in 390

BC by the Greek essayist and general, Xenophon, in

his Anabasis, a description of a 4th-century BC military expedition through Asia Minor.1 But perhaps

the most spectacular manifestation of cold as a

source of attrition in the warfare of the ancient

world was that of Hannibal, who may have lost as

many as 50% of his men, many from hypothermic

injury, while crossing the Alps in 218 BC.

2

The spectrum of cold injury extends from (a)

transient injury to the most superficial layers of the

skin, through (b) full-thickness necrosis of varying

amounts of the soft tissue of the hands and feet, to

(c) fatal systemic hypothermia. By far the most

common medical treatment problems caused by

military operations in cold environments in past

wars have been those associated with damage to

superficial tissues in the extremities. Such local

cold injury is known by a variety of names: immersion foot, trench foot, and frostbite are the best

known. During World War I, cold-induced casualties included 38,000 Italian, 80,000 French, and

115,000 British troops. World War II produced

90,000 cold-induced U.S. casualties and 100,000

German.3 Similar observations are applicable to

more recent wars. During the Korean War, cold

weather contributed to at least 10% of U.S. casualties,3 and during the Falklands War in 1982,

hypothermia and local cold injuries were quite

common.3–5

Systemic hypothermia is less well known but is

certain to be a much greater therapeutic challenge

for military trauma anesthesiologists than is local

cold injury. Strangely enough, not a single official

history of the U.S. Army Medical Department in

World War II mentions this condition, including

Cold Injury, Ground Type, the volume that is dedicated to cold injury.6 It is inconceivable that the

condition did not occur. Systemic hypothermia was

known to contribute to wartime death by drowning. In fact, the Nazi hypothermia “experiments,”

the scientific validity of which has recently been

debunked, were allegedly prompted in part by the

high mortality rate among downed German pilots

and U-boat crews.3,7

It is reasonable to assume that the contribution of

systemic hypothermia to combat mortality was obscured by more-dramatic conditions such as battlefield trauma and disease. Soldiers found frozen to

death on the battlefield and whose demise was

attributed to “exhaustion” or “exposure” were, no

doubt, victims of systemic hypothermia. Certainly,

the nearly 10% of George Washington’s troops who

were reported to perish during the cold winter of

1777 and 1778 died of systemic hypothermia.3,4

Because such casualties die on the battlefield, the

importance of systemic hypothermia would not

have been recognized at the hospital level. With

more rapid means of evacuation from the battlefield, however, it is likely that cases of systemic

hypothermia will be seen more frequently in future

wars.

Soldiers fighting on a wintry battlefield are not

the only candidates for systemic hypothermia. The

battle casualty with substantial blood loss who undergoes a lengthy laparotomy or thoracotomy, and

who receives inadequately warmed intravenous fluids in a suboptimally climate-controlled field hospital, is obviously at risk for developing intraoperative hypothermia—with its attendant potential for

hemodynamic and coagulation abnormalities. The

military anesthesia provider’s experience with systemic hypothermia is much more likely to be based

on casualties who become hypothermic in the operating room than on casualties whose hypothermia

was caused by environmental exposure. Ironically,

hypothermia was recognized as a problem for the

U.S. Army Medical Department during the Persian

Gulf War—a war fought in the desert—but not in

World War II or Korea:

Hypothermia was a frequent and significant clinical problem for combat hospitals. Preoperative and

intraoperative hypothermia consumed vast

amounts of additional oxygen, personnel, and [intensive care unit] resources. DEPMEDS [the Department of Defense’s Deployable Medical Systems] provides for warming blankets for the

operating room beds, but lacks other methods for

active rewarming.8(p10-37)

The infrequent observation of intraoperative hypothermia in past wars may reflect the simple fact

that no device for measuring intraoperative core

temperature has yet been fielded. PROPAQ monitors (manufactured by Protocol Systems, Beaverton,
Systemic Hypothermia

789

Ore.), which are fielded, have a thermistor port, but

the thermistor itself is not part of the DEPMEDS

equipment. DEPMEDS does, however, field a thermometer that reads as low as 21°C, which will

permit diagnoses of hypothermia to be made more

commonly in the future.

NORMAL THERMOREGULATION

Man, like other mammals and birds, is a

homeothermic animal and thus strives to maintain

body temperature within a narrow range despite

changes in environmental temperature. There is a

normal diurnal variation in temperature in healthy

individuals, with the nadir typically occurring between the hours of 0200 and 0400. Oral temperatures of 36.1°C (97°F) are common on morning arising and increase gradually during the day to reach

a peak of 37.2°C (99°F) or slightly higher between

the hours of 1800 and 2200.9 This normal pattern is

not reversed in individuals who work a night shift.

Temperature Measurement

Most scientific literature uses the term core temperature as a basis of reference. The precise definition of core temperature and the most appropriate

site or sites for its measurement have, nonetheless,

been elusive. Despite the inconsistency of rectal

temperature and its lack of intrinsic thermal significance, most clinical knowledge of body temperature depended for years on this site of measurement.10 Tympanic membrane temperature closely

approximates the temperature of the blood supplying the hypothalamus, site of the temperature regulation control center.11 The tympanic membrane,

situated at the base of the middle cerebral fossa and

separated from the internal carotid artery by a thin

layer of bone, would seem the ideal, easily accessible location for measuring core temperature.10,12

With the thermistor tip placed in the mid esophagus, investigators from Yale University determined

no significant difference between esophageal and

pulmonary artery temperatures during either

steady-state conditions or hypothermia and rewarming in patients undergoing cardiac surgery.13 Positioning the esophageal probe where they heard the

loudest heart sounds, anesthesiologists at the Arizona Health Sciences Center showed that esophageal temperature and tympanic membrane temperature have a correlation coefficient greater than

0.75.14 Furthermore, these investigators demonstrated similar correlation for nasopharyngeal and

bladder temperatures. Although conceding that

tympanic membrane temperature (measured in this

study with a Model 6000 monitor manufactured by

Mon-a-therm, Inc., St. Louis, Mo.) best approximates the true value for core temperature, they

recommend using esophageal, nasopharyngeal, and

bladder temperatures because of possible trauma to

the tympanic membrane.14,15 Whichever site is chosen, a device capable of recording low temperatures

must be used so that unsuspected hypothermia will

not be missed.16

Neural Temperature Control

The hypothalamus contains the negative-feedback integrative centers that initiate adaptive responses to perceived changes in temperature. The

central temperature control center responds to a

variety of stimuli including endocrine influences

(eg, the thermogenic effect of progesterone), exercise, sweating, flushing, and mental stress. Peripheral nerve endings innervating the skin, many areas

in the body core, and nervous elements in the spinal

cord and brain stem are known to be sensitive to

temperature changes.17,18 Preoptic anterior hypothalamic nuclei monitor core temperature. The

hypothalamus responds to the rate of firing of

thermosensitive neurons, which is partially dependent on the rate of change of the stimulus. Thus, it

is possible to abolish shivering by slightly increasing skin temperature at the onset of shivering,

thereby allowing core cooling to continue.19 For

example, when deep divers are warmed with

flowing hot water, they may continue to become

hypothermic although their perception is that

they are warm. Radiant heat from a fireplace

may produce the sensation of warmth, prevent

vasoconstriction, and thereby hasten the development of hypothermia in an otherwise cold

room.19 This fact may explain the observation of

Napoleon’s chief surgeon, Baron Dominique

Larrey, who, noting the effects of the Russian

winter on the troops of the Grande Armèe, found

that victims of the cold who were placed closest

to the campfire usually died.3,20,21

Heat Production

At the basal metabolic rate, heat is produced at 40

to 60 kcal per square meter of body surface area per
Anesthesia and Perioperative Care of the Combat Casualty

790

hour.3,22 The ultimate source of heat production is

from the action of adenosine triphosphatase (ATPase) on adenosine 5í-triphosphate (ATP) in the

sodium pump of all biologically active cell membranes.9 The core organs (brain, liver, spleen, heart,

and kidneys) contribute almost 60% of basal heat

production,19 despite constituting only about 10%

of body weight. Nonshivering thermogenesis is

enhanced by an increase in catecholamines, thyroxine, and adrenocorticoids. Basal heat production

can be markedly increased by muscle activity and

shivering.

Preshivering enhancement of muscular tone increases heat production by up to 100%.22 Visible

shivering can increase heat production (and oxygen

consumption) by 500%.23,24 Because of fatigue and

glycogen depletion, this degree of heat production

from shivering is limited to a few hours.22 Thermoregulatory shivering demonstrates a waxing and

waning pattern (4–8 Hz) and differs distinctly from

generalized postanesthetic tremor.25 Unfortunately,

activity and shivering are uneconomical ways to increase heat production because they are often accompanied by increased skin and muscular blood flow,

which further increases heat loss (Figure 28-1).19,23

Heat Loss

Humans are essentially warm-weather, subtropical animals that do not physiologically tolerate or

adapt well to cold environments.4,26,27 Unclothed,

we probably could not survive at temperatures much

below 21°C (71°F).22 Humanadaptation is primarily

behavioral and intellectual: constructing shelters

and acquiring clothes and artificial heat. Thermally, the body can be envisioned as a core, consisting of the vital organs and a shell, the inner layer of

which comprises the skeletal muscle mass, and the

superficial layer of which includes superficial muscle,

subcutaneous fat, and skin.19,21,27,28 Ninety-five percent or more of daily heat production must be lost to

the environment.22 This loss occurs through the

shell and the respiratory tract by radiation, conduction, convection, and evaporation.

Radiation

Radiation (the transfer of heat between objects by

electromagnetic waves) normally accounts for 55%

to 70% of heat loss. The amount of heat loss depends on the temperature gradient between the

body surface and the environment, and the amount

of exposed body surface area. The uncovered head

can be an important source of radiant heat loss. Due

to poor vasoconstriction of the face and scalp, at 4°C

(39°F), one half the total basal metabolic heat production can be lost from an exposed head.19,29

Conduction and Convection

Conduction refers to the transfer of thermal energy through direct contact. Normally, only 2% to

3% of heat loss occurs via conduction to other objects; however, the loss dramatically increases (up

to 5-fold) during contact with cold ground or snow.

Water’s thermal conductivity is some 30-fold greater

than that of air, and immersion causes extremely

rapid heat loss. Approximately 1,500 passengers on

the Titanic died in 0°C water in less than 2 hours.30

Insulation (both clothing and subcutaneous fat) can

prolong survival times.30–32

After heat is moved from the body’s core to the

shell by conduction, it can be dissipated by air

movement over the skin—a process called convection. Heat loss by convection is quite variable and

depends on wind velocity (with the cooling effect

varying approximately as the square root of the

wind velocity)29 and the degree of insulation provided by clothing. Wet garments, rather than trapping air next to the skin and retarding convective

heat loss, become effective conductive heat transmitters.

Evaporation

Evaporation is the conversion of a liquid to its

gaseous phase. The conversion of 1 g of water from

a liquid to a gas requires 0.58 kcal.22,28,29 In humans,

heat loss by evaporation from the skin and respiratory tract generally accounts for 20% of total heat

loss, but this can be increased remarkably by sweating.22,29 Relative humidity and ambient temperature markedly affect the degree of heat loss by

evaporation, with the greatest loss occurring in dry,

cold environments.3

Heat Conservation

By means of a remarkable ability to decrease or

increase blood flow, primarily through cutaneous

arteriovenous shunts33 in the extremities, the human body regulates delivery of heat to its surface.

Cutaneous blood flow can decrease from its normal

300 to 500 mL/min to 30 mL/min and can increase

to more than 3 L/min with maximum vasodilation.22,27,34 Capillary flow, as well as arteriovenous

shunt flow, decreases with higher degrees of vasoconstriction.35
Systemic Hypothermia

791

*Contribution to thermoregulation in a cold environment may be minimal in adult humans

Fig. 28-1. The stepwise and integrated physiological response to cold in the normal human.

Adapted with permission from Reuler JB. Hypothermia: Pathophysiology, clinical settings, and management. Ann

Intern Med. 1978;89:520.



F 29-1

Cold Exposure

Reflex Vasoconstriction

Dorsal Roots

Spinal Thalamic Tract

Thalamus and Reticular System

Thermoreceptors

(gradient between skin and core)

Hypothalamus

(preoptic anterior hypothalamus [POAH])

Mechanism set in gear

Shivering Direct Stimulation of

Skeletal Muscle by

Extrapyramidal Tract

Stimulation of

Pituitary Gland

Sympathetic

Nervous System

Heart Rate Further Constriction

of Skin Vessels

Vasodilation in

Muscle

Rate of Heat Loss

Blood

Flow

Heat Production

Blood Warmed

Negative feedback to the POAH

Thyroid and Adrenal Output

(nonshivering thermogenesis)*

Stimulates
Anesthesia and Perioperative Care of the Combat Casualty

792

DEFINITION AND CLASSIFICATION OF HYPOTHERMIA

In humans, hypothermia is defined as a core

temperature less than 35°C (95°F).3,19,22,28,29 In addition to the hypothermia that is deliberately induced

in certain surgical patients, there are two broad

categories of pathological hypothermia:

1. primary (accidental), in which an otherwise healthy person is exposed to a cold

environment and the thermoregulatory

system’s compensation is inadequate36;and

2. secondary, in which another illness or condition predisposes the individual to accidental hypothermia.3,22,29,36

Further subdivisions into acute and chronic (which

afflicts particularly the elderly who live in insufficiently heated winter houses) and immersion and

nonimmersion have been made.3,36 Another supplemental subclassification distinguishes very rapid

(usually immersion) hypothermia, in which the cold

stress quickly exceeds the body’s ability to produce

heat and maintain core temperature, and intermediate (exhaustion) hypothermia, in which the individual’s heat production is able to maintain core

temperature against a cold stress only as long as

sufficient energy sources are available.19 In very

rapid hypothermia, heat production is unimpaired

and the person will have little difficulty rewarming

on removal from cold stress. In intermediate hypothermia, heat production is markedly impaired when

exhaustion ensues, and “even a relatively mild degree

of cold exposure may be sufficient to cause continued

cooling.”19(p102) (This subject is also discussed in Chapter 23, Metabolic Derangements and Nutritional

Support.) Primary hypothermia is the concern of

this chapter, although military anesthesia providers should bear in mind that they are most likely to

encounter casualties with secondary hypothermia:

injured soldiers in a cold operating room tent.

A number of diverse clinical conditions lead to

impaired thermoregulation, and can generally be

classified as central, peripheral, metabolic, pharmacological or toxicological, and dermatological (Exhibit 28-1). Of these, the most significant are probably

• spinal cord transection, which, by interrupting the spinothalamic tract, breaks the

afferent thermoregulatory loop;

• trauma associated with hypotension and

hypovolemia, which results in generalized

vasoconstriction and decreased metabolic

heat production;

• general anesthetics, which shift the threshold for vasoconstriction and shivering to a

lower temperature range; and

• acute ethanol ingestion, which causes generalized vasodilation and thereby increases

heat loss.

CLINICAL AND LABORATORY MANIFESTATIONS

Hypothermia per se is not lethal to tissue: cellular death occurs only with denaturation when ice

crystals are formed. “What does occur as cells are

gradually cooled is a progressive decrease in functional performance that ultimately kills the

organism.”37(p620) Hypothermia is known to affect

most organ systems, the metabolism, and the blood

and its chemistry (Table 28-1), but the effects of

hypothermia depend on the degree of cooling. Three

stages of hypothermia are commonly recognized:

mild (> 32°C), moderate (32°C–26°C), and severe (<

26°C). Much of the material that follows is summarized in Table 28-2.

Organ-System Effects

Central Nervous System Effects

An initial deterioration in mental status may

progress to dysarthria, incoordination, withdrawal,

irritability, apathy, disorientation, confusion, and

finally to lethargy, intermittent stupor, and frank

coma. Visual evoked potentials decrease38 and the

latency period of somatosensory evoked potentials

is prolonged39 by hypothermia. Although cerebrovascular autoregulation is reportedly preserved

to 25°C,3 hypothermia produces a predominance of

slower-frequency waves on the electroencephalogram, which eventually becomes electrical silence at 19°C to 20°C.3,19 Hyporeflexia progresses

to areflexia and is accompanied by an increase in

rigidity.19

Cardiac Effects

In hypothermia, the usual cause of death is progressive deterioration in cardiopulmonary function. Following an initial increase in heart rate and

blood pressure, hypothermia causes a progressive

bradycardia and myocardial depression, eventu-
Systemic Hypothermia

793

EXHIBIT 28-1

CLINICAL CONDITIONS POSSIBLY RESPONSIBLE FOR IMPAIRED

THERMOREGULATION

Central Nervous System Conditions (Affecting Hypothalamic Function)

Cranial trauma (especially basilar fractures)

Chronic subdural hematomas, and intracerebral hemorrhages

Central nervous system infection

Cerebrovascular accidents

CNS infiltrative lesions including neoplasms, systemic lupus erythematosus, and sarcoidosis

Spontaneous periodic hypothermia

Shapiro’s syndrome (dysgenesis of the corpus callosum)

Wernicke’s encephalopathy

Peripheral Conditions

Neoplasms, especially Hodgkin’s disease and other lymphomas1,2

Peripheral neuropathies

Spinal cord transection*

Trauma associated with hypotension and hypovolemia*

Carcinomatosis

Pancreatitis

Miliary tuberculosis

Myocardial dysfunction with decreased cardiac output

Metabolic Conditions

Hypothyroidism (myxedema)

Hypoglycemia

Hypopituitarism

Hypoadrenalism

Ketoacidosis

Anorexia nervosa

Marasmus and kwashiorkor

Pharmacological/Toxicological Conditions

General anesthetics*

Major conduction anesthetics,(ie, subarachnoid block and epidural)

Ethanol ingestion, acute and chronic*

Barbiturates

Phenothiazines

Benzodiazepines

Cyclic antidepressants

Lithium

Carbon monoxide

Clonidine

Narcotics

Dermatological Conditions

Burns

Epidermolysis bullosum

Exfoliative dermatitis

*Most important

(1) Buccini RV. Hypothermia in Hodgkin’s disease. N Engl J Med. 1985;312:244. (2) Chang M, Gill T. Hypothermia, neurologic

dysfunction, and sudden death in a man with carcinoma. South Med J. 1981;74:1509.
Anesthesia and Perioperative Care of the Combat Casualty

794

ally terminating in asystole or ventricular fibrillation. Some controversy exists over whether asystole

or ventricular fibrillation is the more common terminal rhythm.3,21,40 Rather clearly, the conduction system is sensitive to cold, and both PR and

QT intervals are characteristically prolonged.3

Ventricular irritability develops near 29°C, and

there are reports of ventricular fibrillation in

hypothermic patients induced by mechanical

stimulation secondary to placement of pulmonary artery catheters, esophageal probes, and

endotracheal tubes.19,37,41

The J wave (also known as the Osborne wave) is

said to be present in up to 90% of hypothermic

patients (Figure 28-2).37 This positive–negative deflection immediately follows the QRS complex—

probably caused by delayed depolarization of the

left ventricle—and is occasionally observed in patients with subarachnoid hemorrhage, left ventricular ischemia, and in some healthy young adults.

Respiratory Effects

After an initial increase in respiratory rate following sudden exposure to cold, respiratory rate,

tidal volume, minute ventilation, and the respiratory response to carbon dioxide all progressively

decrease.22,42,43 Despite a decrease in carbon dioxide

production, minute ventilation becomes inadequate

to remove carbon dioxide below approximately

32°C.3,22 The cough reflex and ciliary motility are

depressed, resulting in an impaired ability to deal

with frequently encountered bronchorrhea and pulmonary edema.3,19,22 Autopsy findings often include not only pulmonary edema but also parenchymal hemorrhages.22,44

TABLE 28-1

PHYSIOLOGICAL DERANGEMENTS ASSOCIATED WITH PROLONGED HYPOTHERMIA

System Effects

Central Nervous Incoordination

Disorientation

Confusion

Cardiac Decreased heart rate, mean arterial pressure, cardiac output

Conduction slows, T waves are inverted, QT interval increases

ST elevation occurs between 32°C–33°C (J wave)

Atrial and ventricular fibrillation occur < 30°C

Respiratory Respiratory rate increases early on

Anatomical and physiological dead spaces increase (at 25°C)

Renal Cold diuresis occurs late in the course of the injury, leading to volume depletion,

oliguria, and azotemia

Hematological Hemoconcentration occurs, with increased hematocrit and hemoglobin levels

Disseminated intravascular coagulation can occur from peripheral microvasculature failure

Metabolic Hyperglycemia and mild ketosis

Lactic acidosis

Gastrointestinal Decreased intestinal motility (at < 34°C)

Hemorrhagic pancreatitis is seen occasionally in fatal cases

Notes:

• The metabolism of all drugs is decreased in hypothermia, as is the liver’s ability to detoxify drugs. This should be considered

when administering medications to hypothermic patients.

• In the absence of other overriding medical considerations (eg, severe trauma), no one is dead until warm and dead.

Source: Bellamy RF, ed. Combat Casualty Care Guidelines: Operation Desert Storm. Washington, DC: Office of The Surgeon General,

Walter Reed Army Medical Center, and Borden Institute; 1991: 154.
Systemic Hypothermia

795

TABLE 28-2

CHARACTERISTICS OF THE THREE STAGES OF HYPOTHERMIA

Core Body Temperature

Stage (°C) (°F) Characteristics

Mild 37.6 99.6 + 1 Normal rectal temperature

(> 32°C) 37 98.6 + 1 Normal oral temperature

36 96.8 Increase in metabolic rate

35 95.0 Urinary temperature 34.8°C; maximum shivering

 thermogenesis

34 93.2 Amnesia; dysarthria, and poor judgment develop; normal

blood pressure; maximum respiratory stimulation

33 91.4 Ataxia and apathy develop

Moderate 32 89.6 Stupor; 25% decrease in oxygen consumption

(26°C–32°C) 31 87.8 Extinquished shivering thermogenesis

30 86 Atrial fibrillation and other arrhythmias develop;

poikilothermia; pulse and cardiac output 67% of

normal; insulin ineffective

29 85.2 Progressive decrease in level of consciousness, pulse, and

respiration; pupils dilated

28 82.4 Decreased ventricular fibrillation threshold; 50% decrease

in oxygen consumption and pulse

27 80.6 Loss of reflexes and voluntary motion

26 78.8 Major acid–base disturbances; no reflexes or

Severe response to pain

(<26°C) 25 77 Cerebral blood flow 33% of normal; cardiac output 45% of

normal; pulmonary edema may develop

24 75.2 Significant hypotension

23 73.4 No corneal or oculocephalic reflexes

22 71.6 Maximum risk of ventricular fibrillation; 75% decrease in

oxygen consumption

20 68 Lowest resumption of cardiac electromechanical activity;

pulse 20% of normal

19 66.2 Flat EEG

18 64.4 Asystole

16 60.8 Lowest adult accidental hypothermia survival

15.2 59.2 Lowest infant accidental hypothermia survival

10 50 92% decrease in oxygen consumption

9 48.2 Lowest therapeutic hypothermia survival

extremities produces an initial, relative, central

hypervolemia, which is interpreted as a volume

overload leading to suppression of the antidiuretic

hormone and the well-known cold diuresis. As

Vascular, Renal, and Gastrointestinal Effects

Vascular and Renal Effects. The remarkable

ability of the body to constrict blood vessels in the

Reprinted with permission from Danzl DF, Pozos RS, Hamlet MP. Accidental hypothermia. In: Auerbach PS, Gheer EC, eds.

Management of Wilderness Environmental Emergencies. 2nd ed. St. Louis, Mo: Mosby–Year Book; 1989: 39. In: Danzl DF. Accidential

hypothermia. In: Rosen et al, eds. Emergency Medicine: Concepts and Clinical Practice. 2nd ed. St. Louis, Mo: CV Mosby; 1988.
Anesthesia and Perioperative Care of the Combat Casualty

796

Fig. 28-2. This electrocardiograph shows typical J waves (also called Osborne waves), which follow the QRS complex

that develops at temperatures below 32°C.

renal tubular dysfunction progresses, little of the

glomerular filtrate is reabsorbed, and this, combined with shifts of fluid from the intravascular

space, produces hypovolemia.

Gastrointestinal Effects. Gastrointestinal hemorrhage and pancreatitis are common autopsy findings.21,45 Gastrointestinal motility decreases concomitant with the decline in metabolic rate.

Functional hepatic impairment occurs with little if

any structural damage,37 altering the rate of clearance and metabolism of many drugs.

Metabolic and Hematological Effects

Metabolic Effects. Following an initial increase

in metabolic rate up to 6-fold greater than the basal

rate3,22–24,46 at 35°C, hypothermia slows all metabolic

processes, with the metabolic rate decreasing to

50% of normal at core temperatures of 28°C to

30°C.28,42 A reduction in metabolism and oxygen

consumption of 7% per degree Celsius decrease in

temperature is widely reported.16,42

Hematological Effects. As a consequence of

hemoconcentration and a reported40,47 2% increase in

viscosity per degree Celsius decrease in temperature,

hematocrit usually increases along with significant

“sludging” and interference with tissue perfusion.3,21,36

Platelet and leukocyte counts are frequently depressed

because of splenic and hepatic sequestration.28,42 Platelet sequestration occurring in the portal bed is largely

reversible on rewarming.48,49

Blood Chemistry Abnormalities

Electrolytes and Serum Glucose

Preexisting clinical conditions can result in

transcellular membrane shifts of electrolytes and

produce significant alterations. Unfortunately, there

are no predictable changes in serum sodium, chloride, potassium, magnesium, calcium, or phosphate3,22; therefore, frequent laboratory determinations are necessary during resuscitation from

hypothermia. Cold- and catecholamine-induced

glycogenolysis and decreased insulin secretion37

cause an initial hyperglycemia that proceeds

to hypoglycemia with glycogen depletion.3 Note

that insulin is ineffective below 30°C.3 Therefore,

persistent hyperglycemia during rewarming can

indicate diabetic ketoacidosis, pancreatitis, or

both.

Dissolved Gases and the Acid–Base Balance

The solubility of gases in liquids increases at

colder temperatures; therefore, the partial pressures

of both oxygen and carbon dioxide (PO2 and PCO2)

decrease in the hypothermic patient. The partial

pressure of arterial oxygen (PaO2) declines 7.2% per

degree Celsius decrease, and the partial pressure of

arterial carbon dioxide (PaCO2) declines 4.4% per

degree Celsius decrease.50 Because blood samples

are warmed to 37°C before determination of PO2

and PCO2, temperature correction of both of these

laboratory values was formerly advocated. Such

temperature correction of PO2 is useful clinically. A

PaO2 of 60 mm Hg at 27°C corresponds to a PaO2 of

130 at 37°C.3 The lower PaO2 at 27°C represents not

oxyhemoglobin desaturation but simply a lower

partial pressure of oxygen due to its increased liquid solubility at the lower temperature.

The situation with appropriate evaluation of pH

and PaCO2 is somewhat more complicated but has

now essentially been resolved in favor of not correcting for temperature when measuring pH and

PCO2.

3,51,52 The word correcting is to be understood in
Systemic Hypothermia

797

the following sense: commercially available pH

meters automatically warm a blood sample to 37°C,

the temperature at which the pH is actually measured. There are two options for reporting the

results of this measurement: (1) to report the results

at 37°C or (2) to “correct” them to the original

temperature of the sample. Because pH normally

increases as temperature falls, the uncorrected pH

measured at 37°C will be lower than the pH corrected to the hypothermic casualty’s actual body

temperature.

Studies of cold-blooded (ie, ectothermic) vertebrates show that their blood pH increases and

their PCO2 decreases as their body temperatures

cool.51–53 Some of the decrease in PCO2 results

from the increased solubility of carbon dioxide at

the lower blood temperature, but there is also

decreased carbon dioxide production incident to

the decreased metabolic rate. In these animals,

total body carbon dioxide content3,51 does not

change with decreasing temperature because ventilation decreases less than does metabolism. As

body temperature falls, the pH of the blood of

these animals increases in such as way as to

remain slightly alkalotic. By way of contrast, in

some small hibernating mammals, pH does not

change as temperature falls. These animals

hypoventilate and their total body carbon dioxide increases. Thus, their blood becomes progressively acidotic.

There are two basic approaches to managing pH

alterations during hypothermia, both of which resemble the natural physiological responses described above. In the technique called alpha-stat pH

management, chemical neutrality is maintained by

allowing pH to increase as temperature falls. Conversely, in the approach known as pH-stat management, pH is maintained constant at 7.4 regardless of

the temperature.51,52

Alpha-stat pH management employs uncorrected blood gases, whereas pH-stat management

utilizes corrected gases and strives to maintain a

constant pH of 7.4 regardless of the temperature.

The former term derives from the alpha imidazole

ring on the histidine moiety of various body proteins.51,52 The neutral pH of water (ie, that pH at

which [H+] = [OH–] is 6.8 at 37°C),53 and the normal

0.6 pH units of alkalinity of human blood may well

be important for enzymatic function.3,51–5 In addition,

[m]any essential enzymes (such as lactic dehydrogenase, sodium-potassium-adenosine triphosphatase, and cytochrome C reductase) have been

found to be temperature sensitive and to exhibit

optimum activity when pH is increased during

hypothermia.51(p1643)

The key factor is probably chemical neutrality rather

than a specific hydrogen ion concentration.

Several studies done in endotherms, including

humans, have demonstrated improved cardiac performance and electrical stability when the pH under hypothermic cardiopulmonary bypass was deliberately determined by noncorrected laboratory

values.55,56 For example, the pH determined at 37°C

might be found to be 7.4, which would correspond

to a pH of 7.7 when measured at 28°C. Similarly,

increased cerebral blood flow was also seen when

the noncorrected values for PCO2 and pH were used

and the animals were allowed to remain hypocarbic

and alkalotic.57 In a 1986 study58 of 181 cardiopulmonary bypass patients, 40% of those managed

with the pH-corrected technique developed spontaneous ventricular fibrillation, whereas only 20%

of those managed with the noncorrected technique

did so.

Other authorities have also concluded that pH

correction can be deleterious in the patient with

hypothermia:

Potentially deleterious effects of this alkalosis on

other organ systems have yet to be identified. However, it is clear that maintaining the corrected pH at

7.4 and PCO2 at 40 mm Hg during hypothermia

depresses cerebral and coronary blood flow and

cardiac output, and increases the incidence of lactic

acidosis and ventricular fibrillation. A correction

of pH and PCO2 in hypothermia is unnecessary and

potentially deleterious.3(p46)

In other words, attempting to maintain an actual

pH of 7.4 in a hypothermic casualty will have a

deleterious effect because the corresponding uncorrected pH is profoundly acidotic.

CLINICAL PREVENTION AND TREATMENT

In cold environments, body temperature can be

maintained by increasing body heat production,

decreasing body heat loss, and supplying external

heat sources. However, hospital operating rooms

are kept cool and patients undergoing surgery are

not warmly clothed, so the most practical and efficient methods to decrease heat loss (ie, clothing and

shelter—our primary adaptations to cold) are contravened. This is especially true in field hospitals

that are deployed in tents. The fact that casualties
Anesthesia and Perioperative Care of the Combat Casualty

798

are not kept warm during surgery led directly to the

development of the medical unit, self contained,

transportable (MUST) and DEPMEDS hospitals,

which allowed temperature-controlled interiors.

All anesthetized patients become hypothermic in

rooms cooler than 20°C unless preventive measures

are used.59,60 Ambient temperatures must be 24°C to

26°C to prevent a decrease in esophageal temperature.60 Radiation and convection account for approximately 80% of heat loss, and most of this

occurs during the first hour of anesthesia.42,60 Methods of heat conservation must be a priority of the

operating room staff and must begin before the

casualty is brought into the operating room. In

addition to increasing the ambient temperature, the

operating room staff must also ensure that the casualty—particularly his head—is covered as much as

possible,19 and must minimize evaporative heat loss

from open surgical wounds, especially those of the

trunk.

All the methods described below, except cardiopulmonary bypass, increase temperature rather

slowly, in the range of 0.5°C to 1.5°C per hour.3,61

There is no proof that rapid rewarming improves

survival rates.3

Supplemental Warming Devices

Warm blankets provide some conductive heat

transfer as well as decrease radiant and convective

heat loss.42 Although not available in DEPMEDSequipped hospitals, the “space blanket,” a reflective blanket using aluminized Tyvek (manufactured

by King-Seeley Thermos Co., Winchester, Mass.) is

particularly useful when 60% or more of the body

surface area can be covered.62 In 1980, researchers

conducted a study of patients undergoing major vascular procedures with an average operating room

time of 6 hours. Before they were draped for surgery,

the patients were placed in operating rooms that were

cold (14°C–18°C) or warm (23°C–26°C). The latter

group also received intravenous fluids and blood

that were warmed to 37.5°C and were placed on a

heating blanket at 37.8°C. The researchers were

able to confirm greater heat loss prior to draping in

the cold-room group, but were unable to demonstrate a difference in outcome. The key factor seemed

to be the ability of the patients to compensate for

internal heat loss that had occurred over an extended period of time. Because many procedures do

not last 6 hours, and because the patients in this (and

other) studies initially lose more heat in cold operating rooms,60 operating rooms need to be warmed.42

Placing blankets that contain warm, circulating

fluid between the operating-table mattress and the

patient does not prevent intraoperative hypothermia when used alone.63,64 This finding is not surprising because (a) there is little well-perfused tissue in contact with the blanket and (b) the thermal

conductivity of the usual operating-table mattress

is rather low. (However, these blankets have caused

burns.42) Warmed, humidified, inspired gases used

in conjunction with a warming blanket, however,

produce a synergistic effect and better temperature

preservation than when either is used alone.64

The efficacy of warmed, humidified gases as a

method of conserving heat is easily understood

when it is appreciated that a patient breathing dry

gases at room temperature can consume 25 kcal/h

(about one third of the basal heat production) in

warming that air to body temperature.42,65 Several

studies have demonstrated the efficacy of passive

heat and moisture exchangers in significantly reducing the rate of fall of core temperature,65–67 especially when lower fresh-gas flows are used. In

addition to preventing the expenditure of approximately 25 kcal/h to warm and humidify dry roomtemperature gases,3,42,65 heated (45°C), humidified

gases delivered at 20 L/min provide about 30 kcal/h

heat exchange to a patient with a core temperature

of 28°C (Table 28-3).61

In awake hypothermic volunteers, one group of

researchers68 demonstrated an increase in the rate

of core rewarming of 0.3°C/h for each 10 L/min

increase in ventilation of moist air with an inspiratory temperature of 44°C. Clearly, lesser rates of

heat transfer occur if the gases are cooler and if the

patient’s core temperature is higher.61 Other groups

of researchers61,69 performed their calculations using 45°C as an accepted maximum airway temperature, and still others70 used inspired gases at 42°C to

47°C at the Y connector of the anesthesia tubing.

In one notable study,71 however, researchers studied dogs that had been mechanically ventilated for

6 hours. The group monitored temperatures at the

internal end of the endotracheal tube and demonstrated an acute airway injury consisting of

diffuse mucosal degeneration with focal necrosis,

shedding and sloughing of the pseudostratified

columnar epithelium, and an acute inflammatory

response in the submucosal tissue [when] average

tracheal temperature exceeded 40°C.71(pA490)

These investigators did not control the peak

temperature, however, and report peaks of 46°C

“when the average tracheal temperature was
Systemic Hypothermia

799

TABLE 28-3

ESTIMATED HEAT GAIN FROM ENDOGENOUS AND EXOGENOUS SOURCES

Heat Source Calories Provided at Core Temperature 28°C*

Normal metabolic rate 70 kcal/h

Maximum shivering 350 kcal/h

Heated (45°C) humidified O2 at 20 L/min 30 kcal/h

Heated (45°C) intravenous fluid (1 L) 17 kcal

Heated (45°C) peritoneal dialysis fluid (1 L); 17 kcal

 flow rate 5 L/h over 1h 85 kcal/h

Heated (42°C) cardiopulmonary bypass perfusate (1 L); 17 kcal

 flow rate 28 L/h 476 kcal/h

Trunk immersion in 45°C water:

Vasoconstriction 600 kcal/h

Vasodilation 2,400 kcal/h

*A 70-kg human requires a gain of 60 kcal of heat to increase body temperature 1°C

Reprinted with permission from Bangs C, Hamlet MD. Hypothermia and cold injuries. In: Auerbach BS, Geehr EC, eds. Management

of Wilderness and Environmental Emergencies. New York: Macmillan; 1983: 38. Original data source: Myers RAM, Britten JS, Cowley

RA. Hypothermia: Quantitative aspects of therapy. Journal of the American College of Emergency Physicians. 1979:8(12):523–527.

42°C.”71(pA490) In addition to retarding heat loss

and providing heat gain, heated and humidified

gases stimulate pulmonary cilia and retard coldinduced bronchorrhea.3,72

Blood and Fluid Warmers

Approximately 15 kcal (20% of basal heat production) are required to warm 1 L of 20°C intravenous fluid to 30°C.42,61 Because general anesthesia

ablates shivering and produces increased blood

flow to the skin, rendering the normally homeothermic human a poikilotherm (ie, an ectotherm)17,36,73 and therefore unable to increase caloric

production, a patient’s temperature will decrease

more rapidly when challenged with cold intravenous fluids. The rapid administration of cold (4°C)

blood products represents a considerable thermal

challenge, one that is capable of reducing temperature approximately 0.5°C for every liter transfused

over a 15-minute interval.42 In addition to longavailable heating systems (eg, the Dupaco Hemokinititherm Fluid Warmer, manufactured by

Dupaco, Oceanside, Calif., which uses a countercurrent multiplier system of tubing immersed in a

container of warmed water), the Level 1 Fluid

Warmer (manufactured by Life Systems, Inc.,

Southfield, Mich.), is now available and can warm

fluid and cold blood to 35°C at flows up to 500 mL/

min.74 Additionally, glucose-free intravenous fluids in flexible plastic containers can be preheated in

a microwave oven.3,75,76 (Preliminary testing of the

warming characteristics of each oven should be

done, and the fluid should be thoroughly mixed

before it is administered.3) Packed red blood cells

can be mixed with warm, calcium-free, isotonic

crystalloid,77 or can be prewarmed in a standard

operating room fluid-warming cabinet,78 provided

moderate temperature ranges and proper temperature control are maintained.

Treatment in the Postanesthesia Care Unit

The methods of treatment previously discussed

should be continued for casualties in the postanesthesia care unit who have subnormal temperatures.

To prevent or diminish postanesthesia shivering

and its consequent increase in oxygen consumption, high-risk casualties with temperatures lower

than 35°C should be kept intubated, sedated, and

paralyzed until they are rewarmed. The rewarming

rate is the same when using either radiant heat

lamps or heated blankets changed every 30 minutes,79 and both methods are more effective than
Anesthesia and Perioperative Care of the Combat Casualty

800

only one application of a warmed blanket.80 Radiant heat and other methods of skin-surface warming also prevent or inhibit shivering.19,37,81 A new

device, the Bair Hugger (manufactured by Augustine Medical, Inc., Eden Prairie, Minn.), provides a

microenvironment of warmed air through slits in a

disposable blanket made of paper and plastic. In a

postoperative patient lacking thermoregulatory responses, the Bair Hugger effectively transferred

sufficient heat to increase the mean body temperature approximately 1.5°C/h,82 and should be similarly effective during anesthesia. Spinal and epidural anesthetics may extend the risk of hypothermia

longer into the recovery period than does general

anesthesia, by virtue of the prolonged sympathectomy and associated vasodilation83 combined with

their interruption of afferent fiber activity from

peripheral thermoreceptors.36 But military trauma

anesthesiologists must remember that an awake,

nonshivering, postoperative patient is not necessarily a normothermic one, and rewarming may

well still be required.

Nonhypothermic Shivering

Although the precise mechanism of nonhypothermic shivering remains unclear, even nonhypothermic postanesthetic tremor exacts a high metabolic cost25 and must be curtailed in patients who

are less able to tolerate the increased oxygen consumption. Meperidine, but not morphine or

fentanyl, often stops postanesthetic shivering.84–86

This may be because residual anesthetic inhibits

descending cortical control, which, in turn, results

in reflex hyperactivity.25 A dose of 12.5 mg to 25 mg,

administered intravenously, is effective in 67% to

73% of patients, and 50 mg is successful in 89%.84

Core Rewarming Techniques

The first report of core rewarming appeared in

1957 in Time magazine: 78 L of warm saline was

used as a mediastinal irrigation via thoracotomy.87

Intragastric and intracolonic warm irrigation have

also been used. Cardiopulmonary bypass is the

most rapidly effective means of active body core

rewarming3,21,61 and can, moreover, sustain viability

until adequate myocardial function resumes. Although less effective, hemodialysis is also an effective

modality. Heated peritoneal dialysis is the most efficacious technique of core rewarming, second only to

cardiopulmonary bypass and hemodialysis.3,61,72,88 This

is a relatively simple procedure to perform by either a

“mini-laparotomy” or the percutaneous approach,

using isotonic dialysate at 40°C to 50°C.3,88–90 Peritoneal dialysis with 45°C dialysate at 5 L/h will provide

85 kcal/h, which should increase core temperature

about 1°C/h (see Table 28-3).61

Surface Rewarming Techniques

Although it has been calculated to yield up to

2,400 kcal of heat transfer per hour,61 active external

rewarming by immersing the casualty’s trunk in

45°C water may be dangerous, especially if active

core-rewarming methods are not simultaneously

used.3,30,37,40,91 Reflex vasodilation from external heat

application can cause rewarming shock as circulating

vascular volume in an already hypovolemic core is

diverted to the peripheral circulation.30,37,40,92 This is

a much greater problem in patients with chronic

exposure hypothermia30,61 than in patients with sudden immersion hypothermia, who have not yet developed hypovolemia. In addition, cardiopulmonary resuscitation is impossible with a patient

immersed in a water bath.

An effective field device for surface rewarming

that relies on a charcoal-fueled heating element to

provide energy was developed by the Norwegian

military and is available for use in the U.S. Army:

the Heatpac Personal Heater (manufactured by

Alcatel Innova A/S, P.O. Box 60, Økern, 0508 Oslo

5, Norway; and distributed by Norsk Enterprises

Inc., Alexandria, Va.). The Heatpac is a 23-cm x 12-

cm x 6-cm package weighing 500 g with a combustion time of 6 to 20 hours and heat output of 40 to 250

W. The proprietary charcoal fuel pack weighs 120

to 160 g. The heat energy from charcoal combustion

is distributed via a 1.5-V, D-cell–driven electric fan

and a series of gas ducts. Carbon monoxide pollutants are scavenged by a catalyst. The unit has been

field-tested by the U.S. armed forces and found to

be a practical adjunct in the treatment of hypothermic casualties. The Heatpac has been adapted successfully to the U.S. casualty evacuation bag (National Stock Number [NSN] 6530-01-109-9030). Test

documentation may be requested from Norsk Enterprises Inc. or the U.S. Army Medical Bioengineering Research and Development, Fort Detrick,

Frederick, Maryland 21701-5010. Heatpac is available in the inventories of the North Atlantic Treaty

Organization countries and the U.S. Army:

• the charcoal heater bag is NSN 6530-01-

255-0835,

• the heating unit alone is NSN 6530-01-254-

6492, and

• the charcoal element is NSN 6530-01-254-4130.
Systemic Hypothermia

801

CARDIOPULMONARY RESUSCITATION

not absolutely necessary but is included in the circuit because of the propensity of such patients to

develop ventricular fibrillation—even when treated

prophylactically with antifibrillatory bretylium

tosylate and while avoiding fibrillary stimuli (eg,

chest compression and placement of intracardiac

catheters).

The vulnerability of hypothermic patients to ventricular fibrillation is an important issue. In fact,

some authorities97,98 recommend that CPR be

avoided in the severely hypothermic patient until

asystole or ventricular fibrillation can be electrocardiographically demonstrated. As myocardial tissue cools, the function of the conduction system

degrades and dispersion of relative refractory periods occurs. These phenomena may contribute to

the propensity for malignant dysrhythmias that is

seen with severe hypothermia. A continuum of

effects is seen:

• The higher pacing centers are progressively

inactivated, starting with the sinus node.

• Prolongation of intervals and changes in Twave morphology is noted.

• The terminal deflection of the QRS, the Jwave, is classically seen. (Although

Osborne, their discoverer, asserted that Jwaves were the result of injury, this is now

believed to be unlikely.98)

• At 32°C, atrial dysrhythmias are expected.

• As the core temperature approaches 28°C,

ventricular fibrillation may occur with minimal stimulation.

Unfortunately, these dysrhythmias are refractory

to the standard dosages of antidysrhythmics, as

well as to electrical defibrillation, below 28°C to

30°C.99 This phenomenon included ventricular fibrillation that is unresponsive to lidocaine and

procainamide. Bretylium tosylate has been credited with effective chemical defibrillation,100 following earlier reports wherein bretylium’s prophylactic role, as opposed to its therapeutic one, was

experimentally appreciated.101

Airway security is an important goal in the severely hypothermic patient who is at increased risk

for aspiration. However, endotracheal intubation

itself can cause iatrogenic dysrythmogenic problems. The key is gentle manipulation of the airway

at the time of intubation.102 The goal of minimizing

stimulation during intubation is emphasized.103

Nasotracheal intubation is advocated by some.104,105

The presence of such severe prognostic signs as

rigor mortis; livor mortis; and fixed, dilated pupils

are not reliable criteria for withholding cardiopulmonary resuscitation (CPR) in casualties with hypothermia.3,93 Considerable controversy still exists,

however, regarding the initiation, maintenance, and

techniques of CPR in the pulseless, apneic, severely

hypothermic (< 30°C) person.3,37,94,95 The recommendation to search for a pulse for 1 full minute has

been made.94 The clinical aphorism that a patient is

not dead until he is warm and dead continues to

apply.

CPR requires protocol modification with progressive degrees of hypothermia. This fact is explicitly recognized in the most recent recommendations for the treatment of systemic hypothermia

made by the American Heart Association (Figure

28-3)96; (note that the American Heart Association’s

temperature criteria for the severity of hypothermia

are different from those given in Table 28-2). Patients are divided into two categories by this

protocol: those with both pulse and breathing

present and those with pulse or breathing or both

absent. Those with spontaneous cardiac and respiratory activity are further stratified by core temperature. Above 34°C, passive rewarming (which

in the field means placing the casualty in a warm

environment, or covering with blankets or a warm

sleeping bag) is all that should be necessary. Patients with core temperatures between 30°C and

34°C may benefit, in addition to passive rewarming, from active external rewarming using the

Heatpac Personal Heater. Those whose core temperature is below 30°C and who have a supraventricular rhythm and stable vital signs should

undergo active internal rewarming. In the field,

this means intravenous infusion of warm (43°C)

fluids; breathing warm (42°C–46°C), humidified

oxygen; and, possibly, peritoneal lavage with warm

(43°C), potassium-free fluid.

Active internal rewarming using extracorporeal

bypass incorporating a heat exchanger is an extremely effective modality but is not available in

DEPMEDS-equipped hospitals. A procedure similar to hemodialysis was originally proposed, with

blood being taken from the femoral artery, passed

through a heat exchanger, and then transfused into

the femoral vein. Nowadays, however, femoral

vein–to–femoral artery bypass with a pump is used

because the amount of blood that can be warmed is

greatly increased. If the casualty is being ventilated

and has effective cardiac action, an oxygenator is
Anesthesia and Perioperative Care of the Combat Casualty

802

Actions for all patients:

• Remove wet garments

• Protect against heat loss and wind chill

(use blankets and insulating equipment)

• Maintain horizontal position

• Avoid rough movement and excess activity

• Monitor core temperature

• Monitor cardiac rhythm*

Assess responsiveness, breathing, and pulse

Pulse and breathing present Pulse or breathing or both absent

What is core temperature? • Start CPR

• Defibrillate VF/VT up to a total of 3 shocks

(200 J, 300 J, 360 J)

34°C–36°C (mild hypothermia) • Intubate

• Passive rewarming • Ventilate with warm, humid oxygen

• Active external rewarming (42°C–46°C)†

• Establish intravenous line

• Infuse warm, normal saline (43°C)†

30°C–34°C (moderate hypothermia)

• Passive rewarming

• Active external rewarming

of truncal areas only†‡ What is core temperature?

< 30°C (severe hypothermia)

Perform active internal rewarming

sequence (below)

> 30°C

• Continue CPR

• Give intravenous medications as indicated

(but at longer than standard intervals)

< 30°C

• Continue CPR

• Withhold intravenous medications

• No more than 3 shocks for VF/VT

• Transport to hospital

• Repeat defibrillation for VF/VT as core

temperature rises

Active internal rewarming†

• Warm intravenous fluids (43°C)

• Warm, humid oxygen (42°C–46°C)

• Warm peritoneal lavage (KCl-free)

• Extracorporeal rewarming

• Esophageal rewarming tubes§

Continue active internal rewarming until:

• Core temperature > 35°C, or

• Return of spontaneous circulation, or

• Resuscitative efforts cease

Fig. 28-3. Algorithm for the treatment of hypothermia. CPR: cardiopulmonary resuscitation; VF: ventricular fibrillation; VT:

ventricular tachycardia. Reprinted with permission from Emergency Cardiac Care Committee and Subcommittees,

American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. JAMA. 1992;268:2245.

*This may require needle electrodes through

the skin

†Many experts think these interventions

should be done only in-hospital, although

practices vary

‡Methods include electric or charcoal warming devices, hot water bottles, heating pads,

radiant heat sources, and warming beds

§Esophageal rewarming tubes are widely

used internationally and should become

available in the United States
Systemic Hypothermia

803

It should be borne in mind, as previously mentioned, that avoiding respiratory alkalosis is important. Accordingly, low ventilatory rates (eg, 5

breaths per min) are indicated in the severely hypothermic patient.

The American Heart Association recommendations for managing the pulseless, apneic, hypothermic patient are to begin CPR and to attempt

defibrillation if ventricular fibrillation is diagnosed.

The latter intervention is unlikely to be successful

if the core temperature is below 30°C. Rapid rewarming using a femoral-to-femoral bypass should

begin as soon as possible. An oxygenator is required when the heart is arrested. Blood is taken

from the femoral vein, passed through an oxygenator and heat exchanger, and then pumped back

into the femoral artery. Although in the past,

access to the femoral vessels required their surgical

exposure, there has been increasing success using

percutaneous techniques, which greatly simplifies

this intervention.106 Bypass rewarming is continued until the patient is hemodynamically stable or

cardioversion at 28°C to 30°C is successful. Given

the lack of cardiopulmonary bypass capability in

the combat zone, the only therapeutic option for

hypothermic casualties who are both apneic and

in cardiac arrest is to perform a thoracotomy,

through which open-chest cardiac massage and

warmed saline pericardial irrigation can be carried

out.

Closed-chest cardiac massage in severely hypothermic patients has not been exhaustively studied,

but it has proven to be effective. Recommendations to alter the absolute or relative rates of ventilation and closed chest massage are based on clinical experience and animal experimentation. CPR

rates of massage and ventilation that are one-half

normal are indicated in severe hypothermia. Both

the reduced metabolic demand of hypothermic

patients and the desirability of avoiding potentially deleterious alkalosis underlie the rationale.

One group of researchers investigated changes in

regional blood flow that were the result of hypothermia-induced cardiac arrest in pigs. Initially,

the hypothermic pigs had lower perfusion indices than their normothermic counterparts, probably due to decreases in chest-wall compliance.

Hypothermia reduced the cardiac output 50%;

cerebral blood flow, 55%; and myocardial blood

flow, 31% vis à vis arrested normothermic pigs.

Interestingly, within 20 minutes of cardiac arrest

and initiation of CPR, the normothermic group suffered continued decline in these parameters so that

there was no significant difference between the two

groups.107

The controversial issue of blood-gas interpretation remains unresolved. Nevertheless, treatment

of profound acidosis using the alpha-stat method

has been demonstrated clinically108 in a severely

hypothermic patient. This approach challenges the

recommendation of some authorities22 to defer bicarbonate treatment until the patient’s temperature

has reached 32°C to 35°C.

The determination of death is complicated by not

only the unreliability of pupillary signs but also the

invalidity of electrocardiography and electroencephalography, the standard assessment tools.109

A definitive end point of resuscitation is irreversibility of arrest in a patient whose core temperature

is 35°C or higher.

In addition to the matters previously discussed and

their application to anesthesiologists both inside and

outside the operating room, hypothermia has some

other effects of particular concern to military trauma

anesthesiologists and critical care specialists:

• Minimal alveolar concentrations of halothane and isoflurane decrease with temperature in a manner similar to the decrease in oxygen consumption (ie, a 5%

decrease compared to a 7% decrease in oxygen consumption per degree Celsius decrease in temperature).16,42,110

• Although data do not exist for all drugs

used by anesthesiologists, the functional

hepatic impairment caused by hypothermia increases the half-life of free morphine

from 3.7 minutes at 37°C to 98 minutes at

25°C.37 We can logically deduce that other

narcotics, barbiturates, and benzodiazepines would be similarly affected by hypothermia.

• The effect of neuromuscular blocking drugs

is enhanced and generally prolonged by

hypothermia.111–114

• In addition to its other effects on pulmonary function, hypothermia both significantly increases pulmonary vascular resistance and inhibits hypoxic pulmonary

vasoconstriction.115

OTHER CONCERNS OF SPECIAL INTEREST
Anesthesia and Perioperative Care of the Combat Casualty

804

SUMMARY

Environmental cold has the potential to cause

two significant problems for the military anesthesia provider practicing combat casualty care:

local cold injury, of which frostbite is the best

known, and systemic hypothermia. The morbidity resulting from the former may cause significant attrition, but the condition is unlikely to be

fatal. The importance of the latter as a source of

combat mortality seems to be underrated, possibly because death in such casualties is usually

ascribed to more obvious physical trauma or disease. It may also be that the lack of a means to

accurately measure core temperature in the field

means that there is no way to diagnose systemic

hypothermia.

Normal thermoregulation depends on a sequence

of events that starts with the activation of peripheral thermoreceptors, the integration of the afferent

signals in the preoptic nucleus of the hypothalamus, and the activation of efferent pathways that

cause vasoconstriction in the skin and the fibrillary

contraction of skeletal muscles known as shivering.

The latter mechanism increases the production of

heat, while the former decreases heat loss. The

mechanisms responsible for thermoregulation in

the otherwise healthy combat casualty are likely to

be impaired by the casualty’s trauma—the decreased

heat production associated with shock and the increased heat loss from large, open wounds or surgical incisions—and by the general anesthesia, which,

although it makes possible the needed resuscitative

surgery, may also prevent peripheral vasoconstriction and shivering. To make matters worse, the

casualty may arrive from the field already hypothermic, and the ambient temperature within the

typical combat zone operating room, especially if

the facility has deployed in tents, is likely to be

either too cold or too hot.

It is essential that military anesthesia providers

assure that there is no further cooling of the hypothermic casualty in the operating room. Although

the mildly hypothermic combat casualty (core temperature > 34°C) may initially require only passive

external rewarming, conditions may develop during a long operation that will magnify the heat loss.

External active rewarming, and such active internal

rewarming modalities as intravenous infusion of

fluids heated to 43°C and even peritoneal lavage

with warm saline, should be undertaken prophylactically. Casualties whose core temperatures are

below 30°C will certainly need active internal rewarming, as they are at grave risk of developing

ventricular fibrillation. If available, active internal

rewarming using a pump oxygenator and femoralto-femoral bypass should be instituted. Hypothermic combat casualties who have sustained cardiac

arrest are unlikely to be salvageable. Closed-chest

massage should be started while active rewarming

proceeds. Defibrillation may be possible but is

unlikely to be successful until core temperature

reaches 30°C to 32°C. In lieu of cardiopulmonary

bypass, open-chest cardiac massage with lavage of

the heart and mediastinum with warm saline may

be all that can be done.

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95. Ornato JP. Special resuscitation situations: Near drowning, traumatic injury, electric shock, and hypothermia.

Circulation. 1986;74:(4)23–36.

96. American Heart Association. Emergency Cardiac Care Committee and Subcommittees. American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care. JAMA. 1992;268:2171–2259.
Systemic Hypothermia

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97. Zell SC, Kurtz KJ. Severe exposure hypothermia: A resuscitation protocol. Ann Emerg Med. 1985;14:339–345.

98. Solomon A, Barish R, Browne B, Tso E. The electrocardiographic features of hypothermia. J Emerg Med.

1989;7:169–173.

99. Dronen S, Nowak RM, Tomlanovich MC. Bretylium tosylate and hypothermic ventricular fibrillation. Ann

Emerg Med. 1980;9:335.

100. Danzl DF, Sowers BF, Vicario SJ, Thomas DM, Miller JW. Chemical ventricular defibrillation in severe accidental

hypothermia. Ann Emerg Med. 1982;11(12):698–699.

101. Buckley JJ, Bosch OK, Bacaner MB. Prevention of ventricular fibrillation during hypothermia with bretylium

tosylate. Anesth Analg. 1971;50:587–593.

102. Miller JW, Danzl DF, Thomas DM. Hypothermia treatment. Ann Emerg Med. 1981;10:396–397. Authors’ reply.

103. Miller JW. Hypothermia. In: Kravis TC, Warner CG, eds. Emergency Medicine: A Comprehensive Review. 2nd ed.

Rockville, Md: Aspen Publishers; 1987: Chap 45: 639–656.

104. Miller JW, Danzl DF, Thomas DM. Urban accidental hypothermia: 135 cases. Ann Emerg Med. 1980;9:456–461.

105. Danzl DF, Thomas DM. Nasotracheal intubations in the emergency department. Crit Care Med. 1980;8:677–682

106. Laub GW, Banaszak D, Kupferschmid J, Magovern GW, Young JC. Percutaneous cardiopulmonary bypass for

the treatment of hypothermic circulatory collapse. Ann Thor Surg. 1989;47:608–611.

107. Maningas PA, DeGuzman LR, Hollenbach SJ, Volk KA, Bellamy RF. Regional blood flow during hypothermic

arrest. Ann Emerg Med. 1986;15:390–396.

108. Cohen DJ, Cline JR, Lepinski SM, Brown M, Ireland K.Resuscitation of the hypothermic patient. Am J Emerg Med.

1988;6:475–478.

109. Gregory RT, Patton JF. Treatment after exposure to cold. Lancet. 1972;1:377.

110. Vitez TS, White PF, Eger EI. Effects of hypothermia on halothane MAC and isoflurane MAC in the rat.

Anesthesiology. 1974;41:80–81.

111. Miller RD, Rodericks LL. Pancuronium-induced neuromuscular blockade and its antagonism by neostigmine at

29, 37, and 41°C. Anesthesiology. 1977;46:333–335.

112. Flynn PJ, Hughes R, Walton B. Use of atracurium in cardiac surgery involving cardiopulmonary bypass with

induced hypothermia. Br J Anaesth. 1984;56:967–972.

113. Buzello W, Schluermann D, Schindler M, Spillner G. Hypothermic cardiopulmonary bypass and neuromuscular

blockade by pancuronium and vecuronium. Anesthesiology. 1985;62:201–204.

114. Heier T, Caldwell JE, Sessler DI, Miller RD. Mild intraoperative hypothermia increases duration of action and

recovery time of vecuronium. Anesth Analg. 1990;70:S153.

115. Benumof JL, Wahrenbrock EA. Dependency of hypoxic pulmonary vasoconstriction on temperature. J Appl

Physiol. 1977;42:56–58.
Malignant Hyperthermia

811

INTRODUCTION

CLINICAL SYNDROME

Fulminant Malignant Hyperthermia

Masseter Muscle Rigidity

Stress-Induced Malignant Hyperthermia

BATTLEFIELD RESOURCES

Levels of Equipment Availability

The Clean Anesthesia Machine

The Malignant Hyperthermia Cart

Laboratory Testing

BATTLEFIELD MANAGEMENT

A Fulminant Episode

Masseter Muscle Rigidity

A History of Malignant Hyperthermia

EPIDEMIOLOGICAL AND GENETIC FACTORS

Incidence

Genetics

PATHOPHYSIOLOGY

The Excitation–Contraction Coupling Pathway

Defect Linked to Chromosome 19

Single-Point Mutation of the Ryanodine-Receptor Gene

EVALUATION OF SUSCEPTIBILITY

SUMMARY

STEVEN M. KARAN, M.D.*; AND SHEILA M. MULDOON, M.D.†

MALIGNANT HYPERTHERMIA

Chapter 29

*Major, Medical Corps, U.S. Army; Assistant Professor of Anesthesiology, Uniformed Services University of the Health Sciences

†Chairman, Department of Anesthesiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland

20814-4799
Anesthesia and Perioperative Care of the Combat Casualty

812

INTRODUCTION

Despite screening efforts to remove them from

combat roles, soldiers who are susceptible to malignant hyperthermia will be deployed to the battlefield. A soldier may be unknowingly susceptible, or

may have a first-degree relative who has been diagnosed since the soldier arrived in the combat theater. Rarely, the soldier may have concealed his or

her susceptibility.

The diagnosis and treatment of malignant hyperthermia in the combat environment differs from

that during peacetime. Peacetime care relies on

heightened awareness, capnographic monitoring,

and a readily available supply of dantrolene (the

specific agent for the prevention and treatment of

malignant hyperthermia). This combination has

reduced fatal outcomes to 2% to 3%.1–4 The management of malignant hyperthermia in combat must

rely on diagnosis and treatment in light of the available resources. Therefore, to approach this level of

success on the battlefield, heightened awareness

and increased vigilance, rather than the availability

of advanced monitors, must be emphasized. Although all efforts will be made to provide the

most advanced equipment available, this equipment may not always perform optimally in a

hostile environment.

CLINICAL SYNDROME

Fulminant Malignant Hyperthermia

Malignant hyperthermia is a pharmacogenetic

disorder of skeletal muscle metabolism that is expressed as a broad clinical spectrum. The term

malignant hyperthermia is most commonly used to

refer to a fulminant presentation that begins at the

time of an anesthetic induction, but the spectrum

also encompasses episodes that develop later in the

anesthetic course and progress less rapidly.

Masseter muscle rigidity, which occasionally

progresses to fulminant malignant hyperthermia,

and less well-defined or documented entities (ie,

stress or exercise-induced hyperthermic responses)

are also included in the spectrum. When the susceptible patient is anesthetized with triggering

agents, the fulminant episode presents as tachypnea

and tachycardia that can rapidly progress to arrhythmias, muscle rigidity, and high fever.

Rhabdomyolysis can lead to myoglobinuria, acute

renal failure, and disseminated intravascular coagulation. Death results from arrhythmias, inability to ventilate, cardiovascular collapse, or brain

damage.

A fulminant malignant hyperthermia episode

can occur at induction, hours into a stable anesthetic, in the recovery room, or on the ward. The

rate of progression varies from minutes to hours,

and appears to be independent of the time of onset.

The clinical signs reflect the body’s inability to

respond to an extraordinary increase in metabolic

demand. When the demand can no longer be sustained, organ-system failure occurs and accelerates

the syndrome. The ability to recognize the clinical

syndrome is complicated by (a) its rare occurrence,

(b) the lack of a noninvasive screening test, and (c)

the well-known fact that 50% of patients with

fulminant episodes will have had at least one previous, uneventful exposure to triggering agents. Although contracture testing with halothane and caffeine has been useful in predicting malignant

hyperthermia susceptibility in humans, this test is

unacceptable for general screening due to (a) the

complexity of the testing conditions and (b) its

invasiveness (the testing requires a skeletal muscle

biopsy). For the same reasons, contracture testing

has no place in the management of an acute episode

of malignant hyperthermia. In addition, like all

other diagnostic tests, it is not 100% sensitive or

specific. A detailed discussion of halothane and

caffeine contracture testing follows later in this

chapter.

Potent inhalational anesthetics and succinylcholine can initiate the malignant hyperthermia syndrome in susceptible individuals. Factors that may

influence the onset include

• the patient’s genetic predisposition,

• stress,

• trauma,

• the potency and dosage of the triggering

agent, or

• the presence of nondepolarizing neuromuscular blocking agents or other nontriggering

anesthetics in the anesthetic technique.

Although the exact site (or sites) for the initiation

of the syndrome is still unknown, data on human

subjects and swine document that aerobic and

anaerobic metabolism in skeletal muscle increase
Malignant Hyperthermia

813

very early in the clinical syndrome.5 Elevations in

carbon dioxide and lactic acid production in the

muscle cause both a decrease in venous pH and an

increase in venous carbon dioxide content.6 The

sympathetic nervous system responds to this hypermetabolic state with a massive release of catecholamines, which increases minute ventilation

and cardiac output. Tachycardia and blood pressure elevations appear early. Tachypnea is also an

early sign in patients who are allowed to ventilate

spontaneously; however, this sign is often masked

in controlled ventilation with muscle relaxation

(the current clinical practice). In this setting, elevation of the end-tidal carbon dioxide is the earliest

clinically detectable sign of the syndrome.

Once metabolic demand exceeds the body’s ability to compensate, core temperature begins to rise

because the body is no longer able to dissipate the

heat generated from the skeletal muscle. Temperature can increase more than 1°

C every 15 minutes;

however, this rate will vary depending on conditions such as the ambient temperature, site and size

of the surgical incision, and measures of heat preservation employed for the patient.

In a review of cases published in 1970, (prior to

the discovery of dantrolene therapy) muscle rigidity was found in 70% of the patients.7 The progression of muscle rigidity usually parallels the progression of the clinical syndrome and can interfere

with perfusion and with ventilation. Less frequently,

severe rigidity can occur immediately after the administration of succinylcholine, and has been associated with profound fasciculations. Alterations in

skeletal muscle membrane permeability lead to elevations in serum potassium, sodium, calcium, phosphate, myoglobin, and creatine kinase (CK, formerly called creatine phosphokinase [CPK]).8

Ventricular arrhythmias result from hypoxia,

hyperkalemia, severe acidosis, or increased catecholamine release. Although patients can appear

cyanotic, mottled, or their blood can appear dark in

the surgical field, arterial blood-gas analysis rarely

identifies gross hypoxia. Peripheral vasoconstriction and decreasing cardiac function probably account for regional hypoperfusion, which compounds

the metabolic disorder. Without prompt treatment,

death is inevitable if the syndrome has progressed

to this point. Even after treatment, the patient is at

risk for recrudescence of the syndrome for up to 24

hours.9

Masseter Muscle Rigidity

Trismus, masseter muscle spasm, and masseter

muscle rigidity all describe rigidity of the jaw

muscles after the administration of succinylcholine.

This transient phenomenon occurs despite flaccid

paralysis of the extremities. Tachycardia, ventricular arrhythmias, and elevations in end-tidal carbon

dioxide are common. Discontinuing the triggering

agents usually permits an uneventful recovery; however, progression to the fulminant episode can begin immediately. More commonly, progression to

the fulminant episode develops 20 to 30 minutes

after the resolution of masseter muscle rigidity.

Therefore, monitoring for the syndrome should continue during this period. Serum creatine kinase

levels, which peak 8 to 12 hours after induction, will

be elevated (5,000–10,000 international units) and

can be markedly elevated especially if a second

dose of succinylcholine was administered. Patients

should be monitored postoperatively for the resolution of rhabdomyolysis and myoglobinuria to decrease the risk of renal complications.

The incidence of masseter muscle rigidity progressing to the fulminant episode is unknown, and

until this question is answered, induction techniques that are closely associated with the development of masseter muscle rigidity should be limited.

The incidence of masseter muscle rigidity following

an intravenous induction is greatly reduced compared to that seen with inhalational induction.10

Therefore, the use of intravenous succinylcholine

following induction with a potent inhalational agent

should be avoided.11 If an inhalational induction is

required, intubation can be accomplished with a

short-acting, nondepolarizing muscle relaxant or

by deepening the level of anesthesia. In situations

when rapid airway control is mandatory, no other

muscle relaxant can match succinylcholine’s combination of rapid onset and short duration of action.

The onset time of nondepolarizing muscle relaxants

can be decreased by doubling or tripling the recommended dose for intubation, but this markedly prolongs the duration of action. Before nondepolarizing

muscle relaxants are administered in this fashion,

four factors must be considered:

1. the plan of action if ventilation is not improved following adequate muscle relaxation,

2. the resources available for mechanical ventilation in the postoperative period,

3. the number of soldiers requiring surgical

procedures, and

4. the length of the anticipated surgical procedure.

Although masseter muscle rigidity was originally described as an early sign of malignant hyper-
Anesthesia and Perioperative Care of the Combat Casualty

814

thermia, the validity of this idea and the operating

room management of this condition are being reevaluated.12–14 The following facts have become

accepted:

1. Although masseter muscle rigidity can follow both intravenous and inhalational inductions, it is far more likely in the latter

(1:4,000 vs 1:100).10,15,16

2. Most of the data concerning masseter

muscle rigidity is in the pediatric population, presumably because inductions with

inhalational anesthetics are more frequent

in children.

3. In vitro halothane and caffeine contracture

testing (discussed later in this chapter) is

positive for malignant hyperthermia after

clinical masseter muscle rigidity in approximately 50% of pediatric patients and 25%

of adult patients.17–19

4. Succinylcholine transiently increases the

basal tension of masseter muscles, possibly by a mechanism similar to its action on

extraocular muscles. The relationship between this modest increase in tension and

masseter muscle rigidity or malignant hyperthermia is unknown.20,21

Why the incidence of masseter muscle rigidity is

more common after an inhalational induction remains elusive. Because inductions with inhalational anesthetics are rare in adults, it is unknown if

the incidence in this population is the same as in

children, or if age is a factor. Reporting slight

increases in masseter tension as actual instances of

masseter muscle rigidity may account for some of

the disparity; however, data from one hospital center that examined 42,000 children showed a 10-fold

increase in masseter muscle rigidity following induction with inhalational anesthetics (1:370) versus

induction with intravenous agents (1:3,879).10 When

the incidence of masseter muscle rigidity following

induction with inhalational anesthetics is applied

to halothane and caffeine contracture data, the incidence of masseter muscle rigidity continues to be

markedly higher than the currently accepted incidence of malignant hyperthermia (1:370 • 50% =

1:740). Once the role that inhalational agents or

endogenous catecholamines play in sensitizing the

masseter muscles is determined, we may have a

better understanding of the physiology of this phenomenon. Until then, patients with marked increases in jaw tension (ie, the anesthesia provider is

unable to open the patient’s mouth) should be identified and treated as susceptible to malignant hyperthermia.

Stress-Induced Malignant Hyperthermia

In susceptible swine breeds, the malignant hyperthermia syndrome can be triggered by environmental stresses that include heat, exercise, fear, and

excitement. These stresses have occasionally been

implicated in humans, but convincing and complete data are hard to obtain.22–25 Malignant hyperthermia triggered by combat stress has not been

reported. Patients who are identified as susceptible

to malignant hyperthermia—either by clinical episode or by contracture testing—but who have no

history of an adverse reaction to stress are not likely

to experience an adverse reaction to stress in the

future. Activity need not be limited in this group,

although patients must avoid the triggering anesthetics. If a susceptible patient has experienced a

reaction to stress, that stress and similar stresses

should be avoided or approached with caution.

BATTLEFIELD RESOURCES

malignant hyperthermia patients and therefore will

reduce the amount of resources devoted to their

postoperative care. Clinical suspicion is the cornerstone for detecting malignant hyperthermia in any

environment. This section will also include a discussion of the role of the clean anesthesia machine,

the malignant hyperthermia cart, and laboratory

testing.

Levels of Equipment Availability

The signs of malignant hyperthermia can present

in almost any order or combination. However, the

Combat anesthesia depends on both the battlefield environment and the supply of anesthetic

equipment on the battlefield. Sophisticated techniques can be performed even under austere conditions with a basic minimum of equipment (Exhibit 29-1).26 As new advances in anesthetic

management occur, the specific equipment will

change; however, the principle of optimizing care

with limited resources will not change. To achieve

the goals of early diagnosis and treatment of malignant hyperthermia, the monitors that are available at each level will be evaluated. Achieving this

goal will reduce the morbidity and mortality of
Malignant Hyperthermia

815

EXHIBIT 29-1

LEVELS OF EQUIPMENT AVAILABILITY

• masseter muscle spasm at the time of

intubation,

• increasing difficulty with ventilation, or

• the surgeon’s complaint of inadequate

muscle relaxation.

Late signs will include an elevated temperature

detected by touch or by warm carbon dioxide–

absorption canisters, the exhaustion of carbon dioxide canisters (indicating increased carbon dioxide

production), or dark blood on the surgical field

(indicating a relative hypoxia).

Additional equipment at the second level of availability includes automated blood pressure- and temperature-monitoring devices. Due to high levels of

ambient battlefield noise (like those experienced

during Operation Desert Storm), the automated

blood pressure device may be the only reliable,

noninvasive means for monitoring blood pressure.

Although the temperature monitor provides objective data, its usefulness in diagnosing malignant

hyperthermia is limited: elevated temperature is a

late sign.

Additions at the third level of equipment availability include capnographic and electrocardiographic monitoring. The capnograph identifies one

of the earliest signs of the syndrome and is easily

applied to any anesthetic procedure. This combination makes it an ideal monitor for the detection of

malignant hyperthermia. Changes in venous bloodgas analysis, serum lactate, oxygen consumption,

and cardiac output also occur very early in the

syndrome; but these changes cannot be detected,

continuously monitored, or easily applied to the

battlefield with current monitoring technology.

Although pulse oximetry can alert the clinician to

ongoing arrhythmias, electrocardiographic monitoring is needed for identifying and treating complex arrhythmias. Electrocardiography can also be

useful in detecting changes in serum potassium

levels.

The Clean Anesthesia Machine

A clean anesthesia machine is one that either (a)

has never been used to administer a potent inhalational agent or (b) has been made safe for use with

malignant hyperthermia–susceptible patients. This

item may be taken for granted in most operating

suites in the continental United States, but it is not

included in the equipment provided at any of the

three levels of equipment availability. Three steps

are required to create a clean anesthesia machine

from one that has already been exposed to potent

Equipment Level 1

Ohio 885A Field Anesthesia Machine

Ohmeda Universal Vaporizer Portable Anesthesia System

Pulse oximeter

Basic blood pressure monitoring equipment

Blood-warming and -delivery system

Oxygen source

Fundamental airway and ventilation equipment including suction

Intravenous fluid administration equipment

Intravenous and inhalation drugs

Equipment Level 2

All equipment included in equipment level 1,

plus:

Temperature-monitoring device

Automatic pneumatic blood pressure device

Electric or compressed gas-driven ventilator

Blood autotransfusion equipment

Equipment Level 3

All equipment included in equipment levels 1

and 2, plus:

Capnograph

Invasive blood pressure monitor

Electrocardiograph

Adapted from Condon BC, Temo JM, Crowl FD, et al.

Anesthesia guidelines. In: Bellamy RF, ed. Combat Casualty Care Guidelines: Operation Desert Storm. Washington,

DC: US Department of the Army, Office of The Surgeon

General, and Borden Institute; 1991: 24.

progression of the syndrome usually follows a general pattern (Table 29-1). Because the scope and

availability of laboratory facilities will vary, laboratory signs will be discussed later in this section.

When only the first level of equipment is available,

early diagnosis involves the recognition that nonspecific signs (ie, an elevated heart rate and blood

pressure) are out of proportion to the expected

condition. If the patient is breathing spontaneously

(mechanical ventilators are not included at this

level), tachypnea will probably be the earliest sign.

Rhythm irregularities can be detected by the pulse

oximeter and confirmed with a finger on the pulse.

Skeletal muscle rigidity may be detected by
Anesthesia and Perioperative Care of the Combat Casualty

816

TABLE 29-1

DETECTING CLINICAL SIGNS OF MALIGNANT HYPERTHERMIA AT EACH LEVEL

OF EQUIPMENT AVAILABILITY

Signs of Malignant Hyperthermia

in Common Order of Progression Equipment Equipment Equipment

(top = early; bottom = late) Level 1 Level 2* Level 3†

Increased CO2 production and/or Tachypnea Capnograph

minute ventilation Hot or expired

CO2 canister

Increased O2 consumption Dark blood on

surgical field

Increased cardiac output

Increased pulse Stethescope ECG

Palpation

Pulse oximeter

Increased blood pressure Manual cuff Automated cuff Invasive

monitoring

Arrhythmias Palpation ECG

Pulse oximeter

Rigidity Touch

Ventilation difficulties

Temperature elevation Touch Temperature

Hot CO2 canisters monitor

*Includes means available in Level 1

†Includes means available in Levels 1 and 2

decreased (Table 29-2). Supplies and medications

available for anesthetists are found in two medical

material sets (MMSs, which are discussed in Chapter 6, Deployable Hospitals): MMS D301, Operating

Room, and MMS D306, Pharmacy. Recommendations are under study to create a separate MMS for

anesthesia equipment and medications. Currently,

MMS D301 contains six vials of dantrolene (20 mg

per vial), lidocaine, calcium chloride, epinephrine,

and sodium bicarbonate. Because the average adult

requires 160 to 200 mg of dantrolene at the beginning of treatment, coordination with the pharmacy

will be necessary to ensure the smooth and rapid

administration of the initial dose. An additional 30

vials of dantrolene are contained in MMS D306,

along with procainamide, dextrose 50%, insulin,

mannitol, furosemide, and sterile water. The current supply of sterile water is contained in 5-mL

vials (60 mL of sterile water is required to dissolve

each vial of dantrolene). Therefore, another recommendation has been made to include two 500-mL

inhalational anesthetics. First, because the rubber

parts of anesthesia machines will retain potent inhalational anesthetics, the fresh gas hose, ventilator

bellows, and circuit (if nondisposable) must be replaced with new or disposable parts. Second, the

machine must be flushed with a high fresh gas flow

(10 L/min) for 10 minutes. Finally, the vaporizers

should be removed or drained to prevent any possibility that they will be turned on during the perioperative period. A nonrebreathing system (eg, the

Mapleson or Jackson-Rees anesthesia breathing circuits) can also serve as a clean anesthesia machine

when attached to an oxygen source with adequate

fresh gas flow.

The Malignant Hyperthermia Cart

The rationale for a malignant hyperthermia cart

is to have the supplies required for treatment of

malignant hyperthermia assembled and ready so

the response time for treatment of an episode can be
Malignant Hyperthermia

817

TABLE 29-2

SUPPLIES FOR MALIGNANT HYPERTHERMIA CART

Supply Quantity Purpose

Dantrolene At least 36 vials ——

Sterile water for injection 3 L Reconstitution of dantrolene

50-mL syringes and large-gauge needles 12 Draw up dantrolene

Lidocaine 5 ampules Bolus and continuous infusion

Procainamide 5 ampules Bolus and continuous infusion

Dextrose 50% 4 ampules Treatment of hypokalemia

Mannitol 25% 100 g (8 ampules) Renal protection

Furosemide 200 mg Renal protection

Sodium bicarbonate 50 meq (10 ampules) Treatment of metabolic acidosis

Epinephrine 1 mg (4 ampules) Treatment of hypotension

Calcium chloride 10% 4 ampules Treatment of hyperkalemia

Normal saline (refrigerated) 6 L For injection and irrigation

Also included on the cart: crushed ice or ice maker, irrigating Foley catheter, rectal tube, cooling blanket, central venous access kits,

pulmonary artery catheter, new fresh gas hose, carbon dioxide–absorption canisters, anesthesia breathing circuit,ventilator bellows,

blood-collection tubes, lab slips, labels

bags of sterile water to MMS D301 and four 500-mL

bags of sterile water to MMS D306 for more-rapid

mixing of dantrolene.

Laboratory Testing

Laboratory tests that aid in making the diagnosis

include

• arterial and venous blood-gas analyses;

• serum potassium, glucose, sodium, and

calcium;

• prothrombin and partial thromboplastin

times;

• serum creatine kinase; and

• serum and urinary myoglobin.

Laboratory support will be crucial in confirming the diagnosis of malignant hyperthermia and

in managing advanced cases. Severe metabolic

and electrolyte disturbances require frequent

laboratory analyses in both the initial treatment

and the recovery phases. The most valuable tests

of the initial treatment phase are the arterial

blood-gas analyses and serum potassium levels,

while serum creatine kinase and myoglobin levels are useful in preventing renal damage in the

recovery phase.

BATTLEFIELD MANAGEMENT

Early recognition of the syndrome, discontinuation of the triggering agent or agents, rapid administration of dantrolene, and prompt initiation of

supportive care are the four cornerstones of successful management. It is unlikely that the coordination of this complex process will progress

smoothly unless a plan has already been discussed

and implemented. Although the Malignant Hyperthermia Hotline [(800) 644-9737] is theoretically

available for assistance in the management of suspected cases, communication linkage to this resource from the battlefield is doubtful. The management of the patient with a fulminant episode,

masseter muscle rigidity, and a history of malignant hyperthermia needs to be considered in light

of these constraints.

A Fulminant Episode

Treatment of a fulminant malignant hyperthermia episode requires that two distinct approaches be initiated simultaneously: (1) preparation and administration of dantrolene sodium,

and (2) initiation and maintenance of supportive

care. Assistance from other medical personnel is

essential if these tasks are to be completed rap-
Anesthesia and Perioperative Care of the Combat Casualty

818

* When resources are limited, administer dantrolene first; otherwise,

administer simultaneously with supportive care

†10 units regular insulin in 1,000 mL 10% dextrose in water

‡ If arrhythmias persist or are life threatening, continue to correct

hyperkalemia and acidosis, and administer lidocaine 1 to 2 mg/kg or

procainamide 2–3 mg/kg intravenously as needed. Avoid calcium channel–blocking agents

Ideally, administer simultaneously*

A diagnosis of Malignant Hyperthermia is made

Discontinue all potent inhalation

agents and succinylcholine

Hyperventilate with 100% O2

Repeat initial

dantrolene

dose

Observe the patient for at least

24 h for recrudescence, renal

failure, and disseminated

intravascular coagulation

Follow K+, Na+, Ca++, coagulation

studies, creatine kinase, and

myoglobin until they return to

normal

Continue to follow urinary output,

ECG, and temperature

Inform the surgeon to expedite

or abort the procedure

Administer supportive care

Monitor for

Rx

Cool patient by placing

ice packs to the axilla

and groin; using cold

solutions for lavage,

irrigation, and intravenous fluid therapy

Rx

Bicarbonate

Hyperventilation

Rx

Insulin/Glucose†

Bicarbonate

Diuretics

Hyperventilation

Calcium chloride

Rx

‡

Correct elevated K+ and

acidosis

Lidocaine or

procainamide

Rx

Intravenous fluids

Mannitol

Lasix

Temperature elevation

Tailor response to

magnitute of elevation;

avoid hypothermia

Acidosis

Monitor via serial bloodgas analysis

Hyperkalemia

Monitor serum potassium

and glucose

Arrhythmias

Monitor via ECG or pulse

Urinary output

Place Foley catheter

Maintain urinary output >

1 mL/kg/h

Administer dantrolene 2.5 mg/kg intravenously, and

repeat unless patient responds with a decrease in

ETCO2, temperature, rigidity, or heart rate

Obtain assistance from

Other anesthesiologists

Surgeons

Nurses

Corpsmen

Limited, late, or

no response

Early response

Administer dantrolene 1 mg/kg/h

until laboratory values and signs

stabilize

Monitor for

Heart rate

Temperature

ETCO2 and

PaCO2

No early

response

Malignant Hyperthermia Hotline

(800) 644-9737

Hotline is available 24 h/d and

is designed to provide direct

consultation with an expert to

assist in the management of

acute cases

Fig 29-1. Management of a patient with fulminant malignant hyperthermia. The Malignant Hyperthermia Hotline

should be contacted as soon as possible after the working diagnosis is made.

Reconsider

the differential

diagnosis (see

Exhibit 29-2)
Malignant Hyperthermia

819

idly and with the recommended priority (Figure 29-

1). If another anesthesia provider is unavailable, an

operating room nurse or technician or a surgeon can

assist.

Potent inhalational agents and succinylcholine

infusions must be stopped and the patient

hyperventilated with 100% oxygen at high rates of

flow. These two actions will limit the patient’s

exposure to the triggering agents and enhance the

elimination of the inhaled agents. Switching to a

clean anesthesia machine will further enhance the

elimination of inhaled agents; however, this task is

usually difficult, time-consuming, and unnecessary.

In less severe cases, or in brief exposures, these two

actions may be adequate to stop the syndrome. In

severe cases, even vigorous manual ventilation cannot return carbon dioxide levels to normal. Even if

the syndrome is halted with supportive care alone,

the administration of dantrolene is still recommended because resources for observation in an

intensive care unit may be extremely limited.

Dantrolene Therapy

Intravenous administration of dantrolene

(2.5 mg/kg) is recommended, as dantrolene not

only reverses the episode but also decreases the

postoperative complications. Myocardial depression or severe rigidity can lead to inadequate muscle

perfusion and therefore limit the delivery of the

drug to its site of action.27 If the patient does not

respond to the first bolus, additional doses should

be administered until decreased carbon dioxide,

temperature, rigidity, and heart rate have been

achieved. Once the acute episode is controlled,

dantrolene should be continued at 1 to 2 mg/kg/h

for a minimum of 2 hours, or until the clinical and

laboratory signs have returned to baseline (with the

exception of creatine kinase and myoglobin).

Dantrolene is supplied in a lyophilized form and

has a shelf life of 3 years. It is reconstituted with

sterile water (50 mL for each 20-mg vial) due to its

high osmotic content. Dantrolene is almost insoluble in water, but the manufacturer’s addition of

mannitol (3 g) and sodium hydroxide to each vial

has rendered the drug soluble and therefore preparation time has been reduced to 2 to 3 minutes. The

pH of the reconstituted solution is 9.5; therefore,

dantrolene should be administered in a large vein

to decrease the risks of thrombophlebitis and tissue

necrosis from extravasation.

Dantrolene is the most effective treatment for

both arrhythmias and elevated temperatures because it reverses the abnormal metabolic state.

Arrhythmias result from the combination of hypoxia, acidosis, hyperkalemia, hypercarbia, and

elevated endogenous catecholamines. Lidocaine

(1–2 mg/kg) or procainamide (2–3 mg/kg) should

be administered as needed for persistent or lifethreatening arrhythmias. If control of heart rate

is necessary, short-acting β-adrenergic blocking

agents should be used instead of calcium channel–

blocking agents. (Hyperkalemic cardiovascular

collapse has been reported with the combination

of dantrolene and calcium channel–blocking

agents.28,29)

Recrudescence

After an adequate clinical response, tachycardia

may return as the patient emerges from the anesthetic. A titration of narcotics or benzodiazepines is

useful in this situation. Recrudescence of the syndrome is managed with the same urgency as the

original episode. Recrudescence has occurred up to

24 to 30 hours later; therefore, continued monitoring in the postoperative period is advocated.9

 If the

patient fails to respond or only partially responds to

appropriate therapy, then treatment of malignant

hyperthermia should continue but other diagnoses

should be considered (Exhibit 29-2). Pheochromocytoma and thyroid storm mimic malignant

hyperthermia and can be confused with malignant

hyperthermia crises.

EXHIBIT 29-2

DIFFERENTIAL DIAGNOSIS OF

MALIGNANT HYPERTHERMIA

Hypoxia

Hypercarbia

Sepsis

Light anesthesia

Thyroid storm

Pheochromocytoma

Drug reaction

Cocaine toxicity

Intracranial trauma

Neuroleptic malignant syndrome

Hypoxic encephalitis

Factitious malignant hyperthermia

Iatrogenic hyperthermia
Anesthesia and Perioperative Care of the Combat Casualty

820

Therapeutic Cooling

Lowering the patient’s temperature reduces oxygen consumption and prevents brain injury. Core

cooling, which is more effective than surface cooling, is accomplished by using refrigerated solutions

for gastric and rectal lavage, wound irrigation,

and intravenous infusion. Surface cooling is more

effective when ice packs are placed in the groin

and axilla. Drastic cooling of the room or placing

the patient in an ice bath may actually be counterproductive, as they will induce shivering and vasoconstriction. Once the patient’s temperature is

controlled, continued monitoring is necessary to

detect hypothermia or recrudescence of the syndrome.

Acid–Base Disturbances

Serial measurements of arterial blood gases are

essential for assessing and correcting the metabolic

and respiratory acidoses as well as in evaluating

the effectiveness of therapy. Overaggressive bicarbonate therapy risks severe alkalosis and requires

additional ventilation to eliminate the excess carbon dioxide produced. During rapid ventilation,

a stable plateau phase may be impossible to obtain

on the capnogram. Therefore, blood-gas analysis

is necessary to validate the accuracy and trend of

the capnograph. Finally, arterial blood-gas analyses can be used to determine oxygen consumption

if cardiac output and mixed venous oxygen are

known.

Hyperkalemia

The most life-threatening serum abnormality is

hyperkalemia. It results from leakage out of damaged muscle cells and from acidosis when a hydrogen ion is exchanged for a potassium ion. This

abnormality should be corrected with glucose, insulin, and bicarbonate therapy. Hypokalemia can

follow the initial hyperkalemia; therefore, frequent measurements of serum potassium and glucose are required. Currently, calcium therapy is

reserved for life-threatening arrhythmias or inotropic support, as it may increase intracellular calcium

levels through calcium-induced calcium release.

Hypocalcemia, which is common and detected on

the electroencephalogram as a prolongation of the

QT interval, is refractory to calcium therapy.

Changes in phosphate, sodium, and chloride may

also occur and usually correct with control of the

syndrome.

Late Complications

Late complications include renal failure, disseminated intravascular coagulation, and neurological

deficits. Reversal of these complications is difficult

and frequently not possible; therefore, early diagnosis and treatment are essential to limit or prevent

damage. Renal protection is achieved by maintaining urinary output at 1 to 2 mL/kg/h and should

continue until urinary myoglobin has cleared and

creatine kinase levels have peaked. Central venous

pressure monitoring can be helpful in guiding this

therapy. Creatine kinase and urinary myoglobin

elevations usually peak 12 to 24 hours after the

event, and should be followed every 8 hours until

they approach baseline. They reflect the destruction of skeletal muscle and leakage of enzymes from

intact skeletal muscle cells, possibly due to increased

intracellular osmotic pressure.30 Continued elevation of these parameters can indicate a partially

treated case or recrudescence of the syndrome.

Disseminated intravascular coagulation results from

hemolysis, released tissue thromboplastin, and

hypoperfused tissue. Serial laboratory evaluation

of prothrombin time, partial thromboplastin time,

fibrinogen, and fibrin split products will help to

identify this complication before clinical signs appear. Treatment of disseminated intravascular coagulation in malignant hyperthermia is managed as

it is from any other source. Neurological complications include delayed awakening (possibly due to

cerebral edema) and permanent neurological deficit secondary to hypoxia or hypotension.

Masseter Muscle Rigidity

When an anesthetized patient is found to have

masseter muscle rigidity, the anesthesia provider

has three treatment options:

1. Cancel the operation.

2. Continue the operation but convert to a

nontriggering anesthesia technique.

3. Continue the operation as planned.

The differential diagnosis of a “stiff jaw” must also

be considered and ruled out (Exhibit 29-3). The

status of the patient, the estimated length of the

surgery, the resources available to initiate and sustain treatment of a fulminant episode, and the anesthesia provider’s own familiarity with the treatment of malignant hyperthermia must all be

considered. The conservative approach, option 1,

is to stop the anesthetic, observe for signs of ma-
Malignant Hyperthermia

821

options, 1 and 2, appear better suited for the treatment of masseter muscle rigidity.

A History of Malignant Hyperthermia

Soldiers who are susceptible to malignant hyperthermia are not eligible for combat duty. Despite

this policy, however, the situation will undoubtedly arise in which a wounded soldier reports with

a questionable or even a documented history of

malignant hyperthermia. In combat, there will be

no practical means to document a questionable history; therefore, the management of such a casualty

will not differ from that of a soldier with a documented history. Whenever possible, the casualty

should be evacuated to a combat support hospital,

where equipment and personnel are less limited. If

evacuation is not possible, a safe anesthetic can be

administered with additional preparation. The anesthetic technique will depend on both the casualty’s

condition and the proposed procedure, and may

involve monitored care, regional anesthesia, or a

nontriggering general anesthetic technique. Whichever technique is chosen, the anesthetic machine

must be prepared, dantrolene must be on hand, and

extra personnel should be alerted in anticipation of

any signs of malignant hyperthermia. The rubber

parts of the field machine will retain potent inhalational anesthetics and therefore must be replaced

with new or disposable parts, and flushed clear

with a high fresh gas flow.31 The vaporizer should

be drained or removed.

When time is limited, an alternative to the field

anesthesia machine is a clean Mapleson system

with an oxygen source. If possible, use either the

operating room with the best ventilation system or

the one in which the lowest level of potent inhalational agents was used that day. If the operating

rooms are designed to accommodate two separate

anesthetizing locations in the same room, arrangements should be made so that a triggering anesthetic is not being administered at the second location. End-tidal carbon dioxide monitoring should

be used whenever possible. Because nitrous oxide

will probably not be available, nontriggering techniques that do not rely on this agent must be employed. Intravenous techniques include infusions

of pentothal, ketamine, narcotics, or propofol; titrated combinations of benzodiazepines; ketamine

and narcotics; or neuroleptic anesthesia. An extended observation period (4–6 h) is required, and

the recovery personnel must be educated in the

signs of malignant hyperthermia. Although most

Malignant Hyperthermia Hotline consultants no

EXHIBIT 29-3

DIFFERENTIAL DIAGNOSIS OF

MASSETER MUSCLE RIGIDITY

lignant hyperthermia and renal dysfunction, identify the patient as susceptible to malignant hyperthermia, and return to the operating room another

day with a nontriggering anesthetic.1,3 This approach is supported by the facts that (a) morbidity

and mortality continue to be associated with malignant hyperthermia and (b) the anesthesia provider

cannot predict the severity or progression of the

syndrome once masseter muscle rigidity is identified. Discontinuing the anesthetic is the safest

approach in the face of limited resources, but will

not be possible when the surgery is life or limb

saving. When surgery must be performed, convert

to a nontriggering technique, administer dantrolene 2.5 mg/kg, maintain adequate urinary output,

and proceed with the surgery with heightened vigilance.

In options 2 and 3, surgery is permitted to proceed even when it is not emergent. Clinical malignant hyperthermia only infrequently follows masseter muscle rigidity; therefore, the argument can

be made that the operation can continue as long as

the anesthesia provider is equipped to monitor for

malignant hyperthermia and to treat it if the syndrome occurs. Supporters of option 2 believe that

masseter muscle rigidity is part of the spectrum of

malignant hyperthermia; therefore, they convert to

a nontriggering technique to prevent further exposure.2 The patient is (a) identified as susceptible to

malignant hyperthermia and (b) administered only

nontriggering anesthetics for future surgeries. Supporters of option 3 do not believe that masseter

muscle rigidity is part of the spectrum of malignant

hyperthermia.10,14 Following this reasoning, triggering agents are continued.

All three options have limited support in the

literature, but more information is needed to determine the true relationship of masseter muscle rigidity and malignant hyperthermia. Until this question is answered adequately, the conservative

Inadequate skeletal muscle relaxation

Temporomandibular joint disease

Myotonia congenita

Abnormal physiological response to

 succinylcholine
Anesthesia and Perioperative Care of the Combat Casualty

822

longer believe that pretreatment with dantrolene

(2.4 mg/kg, administered intravenously) is required,

the decision to pretreat with dantrolene is left to the

individual anesthesia provider and circumstance.

While preoperative administration of dantrolene

will provide a measure of reassurance to the clinician in an emergent situation or when the certainty

of a clean environment is questionable, it may deplete a limited supply of the drug or cause postoperative weakness in the patient. Oral dantrolene

premedication has no place in this setting. If

dantrolene is administered, a Foley catheter is required because the mannitol in the intravenous

formulation has a diuretic effect.

TABLE 29-3

INHERITANCE PATTERN OF 93 FAMILIES

WITH MALIGNANT HYPERTHERMIA

Adapted with permission from McPherson EW, Taylor CA. The

genetics of malignant hyperthermia: Evidence for heterogeneity. Am J Med Genetics. 1982;11:277.

Clearly autosomal dominant 38

Possibly autosomal dominant 14

Associated with dominant myopathies 3

Isolated 17

Questionable recessive (isolated) 21

Insufficient information 7

Present in Families

Genetic Pattern (%)

EPIDEMIOLOGICAL AND GENETIC FACTORS

Incidence

The prevalence of the malignant hyperthermia

gene and the incidence of the syndrome remain

unknown in the general population. Determinations of prevalence and incidence are complicated

by the following factors:

• The human genetic defect or defects responsible for the malignant hyperthermia

syndrome remain elusive.

• The presentation of the clinical syndrome

is variable.

• Greater awareness of the disease has resulted in treatment of suspicious episodes

before true diagnosis-confirming signs

develop.

• A simple and accurate screening test is

lacking.

In light of these difficulties, the incidence of

malignant hyperthermia is estimated to be in the

range of 1:4,200 to 1:250,000 anesthetics, depending

on the patient population and criteria used in the

analysis.7,32,33 It is impossible to predict (a) whether an

episode of malignant hyperthermia will occur in the

operating room during the next armed conflict or

(b) if an individual soldier is susceptible to malignant hyperthermia. No acute episodes of malignant

hyperthermia were reported during Operation Desert

Storm. However, seven soldiers were identified as

susceptible (via their family histories) and removed

from the combat area for further evaluation. Susceptible soldiers probably will be deployed during

future conflicts, but their number is likely to be small.

Although at this time it is impossible to influence

the incidence of malignant hyperthermia in the

military, proper planning and vigilance will limit

the morbidity and mortality of this disease. Fatal

outcomes continue to decline. Since 1970, mortality

has fallen from 70% to 2% to 3%; this decline is a

direct result of both widespread education of anesthetists concerning malignant hyperthermia and

the availability of dantrolene therapy.4,7

Genetics

An autosomal dominant pattern of inheritance

was suggested in the first reported case of malignant hyperthermia.34 Features of this mode of inheritance are that it (a) appears in every generation,

(b) is transmitted to approximately one half the

offspring of affected family members, (c) does not

appear in the offspring of unaffected family members, and (d) is not influenced by the gender of the

affected family member for transmission. However, as more families were investigated, the autosomal dominant pattern was not always evident. In

1982, the families of 93 malignant hyperthermia–

susceptible patients were reviewed to determine

their mode of inheritance.35 Only 52% of the families were identified as clearly or possibly autosomal

dominant (Table 29-3). The concept of multiple

gene defects as an explanation for the apparent

heterogeneity of the syndrome has several supporters.35–37 The inheritance of malignant hyperthermia

will remain incompletely understood until the genetic defect or defects that give rise to malignant

hyperthermia are identified.
Malignant Hyperthermia

823

PATHOPHYSIOLOGY

The clinical presentation of malignant hyperthermia is the result of abnormal calcium regulation

in skeletal muscle following exposure to triggering

anesthetic agents. Original theories postulating a

central nervous system origin for malignant hyperthermia could not explain why the syndrome was

initiated in a caudal animal preparation or following total spinal blockade.5,38 The sympathetic nervous system was ruled out as the initiating site for

malignant hyperthermia when researchers studying swine found that metabolic changes preceded

increases in sympathetic tone and temperature.39

Data from the same study also showed that uncoupling of oxidative phosphorylation could not explain the heat production during a malignant hyperthermia episode. A distinctive myopathic defect

is unlikely in malignant hyperthermia. Skeletal

muscle from susceptible individuals usually exhibits no characteristic histological defect; however,

variable nonspecific changes are seen. Conclusive

evidence supporting skeletal muscle as the functional site of the defect has been found in both the

swine model and in human data.40,41 These data

include

1. the observation that during a fulminant

episode, a patient experienced total-body

rigidity, with the exception of the one extremity that was protected by a tourniquet;

2. the development of in vitro contractures to

halothane in biopsied muscle samples from

susceptible patients; and

3. elevated levels of creatine kinase and

myoglobinemia following fulminant episodes.

The Excitation–Contraction Coupling Pathway

A brief review of the excitation–contraction coupling pathway will provide a framework to understand the current theories in the pathogenesis of

malignant hyperthermia (Figure 29-2). Although

normal excitation–contraction coupling is not completely understood, skeletal muscle contractions

start with an action potential at the neuromuscular

junction that rapidly spreads over the sarcolemma

and into the transverse tubule (T) system (invagination of the sarcolemma).42 This electrical signal

results in the rapid release of calcium from the

terminal cisternae of the sarcoplasmic reticulum. It

is yet to be discovered how the signal traverses from

the T system to the sarcoplasmic reticulum, but a

calcium-release channel that forms a bridge between the two structures has been identified.43 This

channel is now known as the ryanodine receptor.

Ryanodine, an alkaloid insecticide, binds to the

channel with high affinity and specificity and causes

skeletal muscle contraction. During normal skeletal

muscle contraction and relaxation, the calcium-release channel will close shortly after activation. The

myoplasmic calcium concentration reaches a plateau and therefore facilitates relaxation by allowing

calcium uptake to exceed calcium release. Skeletal

muscle relaxation is accomplished by the return of

calcium to the sarcoplasmic reticulum. Calcium

uptake into the sarcoplasmic reticulum is an active

process performed by a calcium pump, the major

portion of which is a 100-Kd (kilodalton) protein.

Early investigations noted that skeletal muscle

from susceptible individuals developed contractures

at lower caffeine concentrations than normal

muscle.44 This focused investigators’ attention on

the sarcoplasmic reticulum, because caffeine produces contractures in skeletal muscle at that site. 45

However, biochemical studies failed to reveal either the specific defect in sarcoplasmic reticulum or

a site where anesthetic agents would increase the

release of calcium. Because calcium regulation is

the primary function of the sarcoplasmic reticulum in skeletal muscle, calcium regulation in the

excitation–contraction coupling pathway was also

investigated.

The identification of dantrolene’s pharmacological site of action supported this approach, because

its site of action is thought to be somewhere between the transverse tubule and the sarcoplasmic

reticulum.27 Direct evidence of defective intracellular calcium regulation was provided by two separate methods of measuring myoplasmic calcium

concentrations. In one study46 utilizing fura-2 (an

intracellular calcium-selective dye), elevations in

myoplasmic calcium were found to correlate with

the force of in vitro contracture in susceptible swine

muscle induced by halothane or caffeine. In the

other study,47 calcium-selective microelectrodes

detected myoplasmic calcium concentrations that

increased when the malignant hyperthermia syndrome was triggered in swine, and reversed following the administration of dantrolene. Prolonged

elevation of myoplasmic calcium (a) produces

muscle contracture and a sustained contraction and

(b) appears to be the source of the metabolic disturbances during a malignant hyperthermia episode.
Anesthesia and Perioperative Care of the Combat Casualty

824

Fig. 29-2. This skeletal muscle transverse tubule–sarcoplasmic reticulum system illustrates the cellular components

involved in excitation-contraction coupling. An action potential begins at the top right corner of the figure and

traverses the sarcolemma and transverse tubules, as the arrows depict. This electrical activity is transformed into the

release of calcium from the terminal cisternae of the sarcoplasmic reticulum. Although the exact mechanism is unclear,

the dihydropyridine receptor on the T-tubular membrane and the nearby calcium-release channels and ryanodine

receptors on the terminal cisternae appear to have major roles. During normal excitation–contracting coupling,

calcium is released from the terminal cisternae through the open calcium-release channels. This increases the

myoplasmic calcium concentration and initiates contraction. Closure of the calcium-release channels and uptake of the

myoplasmic calcium by the calcium pumps have the net effect of decreasing the myoplasmic calcium concentration,

thus limiting contraction. In malignant hyperthermia, calcium hemostasis is abnormal, as evidenced by elevated

myoplasmic calcium concentrations. The elevated myoplasmic calcium concentrations may be the result of an

abnormality of the dihydropyrimidine receptor, ryanodine receptor, or some modulator of these receptors. Adapted

with permission from Muldoon SM, Karan SM. Hyperthermia and hypothermia. In: Rogers MC, Tinker JH, Covino BG,

Longnecker DE, eds. Principles and Practice of Anesthesiology. St Louis, Mo: Mosby–Year Book; 1993: 2504.

Either alone or in combination, exaggerated calcium release or depressed calcium uptake can produce an elevation of the myoplasmic calcium concentration.

Because calcium uptake appears to be unaffected

in susceptible muscle, recent investigation is focused on identifying defects in calcium release or

regulation. This approach is supported by the facts

that (1) dantrolene has no effect on calcium uptake

in the sarcoplasmic reticulum and (2) dantrolene

also reduces calcium release in the sarcoplasmic

reticulum.28 A mechanism for abnormal calcium

release was first described in 1981, when a researcher

postulated that calcium-induced calcium release

was responsible for the abnormal contractures induced by caffeine or halothane in biopsied skeletal

muscle from malignant hyperthermia–susceptible

patients.48 (The term calcium-induced calcium release describes the observation that skeletal muscle

sarcoplasmic reticulum will release calcium when

calcium is applied to its cytoplasmic surface.) Calcium-induced calcium release is activated by calcium, halothane, and caffeine, and is inhibited by

high magnesium, calmodulin, tetracaine, and ruthenium red49,50; it is also associated with the sarcoplasmic reticulum terminal cisternae, site of the

ryanodine receptor, and may be activated or inhibited by ryanodine.51 Abnormal calcium-induced

calcium release has also been reported in the swine

model. While one researcher52 reports that susceptible swine have a lower calcium threshold to initiate calcium-induced calcium release, others53 report that susceptible swine have a higher rate of

calcium-induced calcium release. To date, biochemical evidence of a ryanodine receptor abnormality

exists only in swine.54 Other investigators suggest
Malignant Hyperthermia

825

that the calcium-release channel is normal but the

structures that modulate its function are abnormal.55,56 Alternative theories to a defect in the

ryanodine receptor include the dihydropyridine

receptor,55 hormone-sensitive lipase,56 phospholipase A2,

57 and inositol 1,4,5,-triphosphate phosphatase58 deficiency. In light of the broad spectrum

of clinical presentation of malignant hyperthermia,

more than one defect will probably be identified

with the malignant hyperthermia syndrome. Advances in genetic analysis may provide some answers for this complex disease.

Defect Linked to Chromosome 19

The first major genetic breakthrough was the

linkage of a possible malignant hyperthermia defect to chromosome 19q12-13.2 by two independent

laboratories (Figure 29-3).59,60 Linkage is said to

occur when two distinct genes on the same chromosome tend to be inherited together. The likelihood

of linkage is increased as the distance between the

genes is decreased. The lod score (logarithm of the

odds) quantifies the likelihood of linkage. Linkage

is considered proven when the lod score is 3 (1,000:1

in favor of linkage) and ruled out when the lod score

is –2. With the knowledge that porcine malignant

hyperthermia is genetically linked to the glucose

phosphate isomerase (GPI) locus, a team of researchers examined three extended Irish families who

expressed malignant hyperthermia susceptibility

as an autosomal dominant trait for linkage to the

human GPI locus.59 Human GPI was previously

mapped to chromosome 19q12-13.2, an area with

several well-defined polymorphic loci from which

lod scores could be determined. The lod score for

linkage between malignant hyperthermia susceptibility and the genetic marker CYP2A was 5.65. The

researchers concluded that in both humans and

swine, malignant hyperthermia is probably due

to mutations in homologous genes, and that the

malignant hyperthermia defect in humans is probably located in the CYP2A area. Other research

supports this conclusion by demonstrating a linkage (lod score 4.20) between the ryanodine receptor gene and malignant hyperthermia susceptibility in nine families with ryanodine gene

polymorphisms (two or more expressions of the

same gene).60 Eleven families in the study did not

exhibit polymorphism of the gene; this suggests

another genetic site for the malignant hyperthermia defect.

Fig. 29-3. Regional localization of gene and DNA-segment markers on chromosome 19. This type of genetic map only

gives information as to the sequence of markers on a gene, but gives no information as to the size of the marker or the

distance between markers. Using lod scores (logarithm of the odds), researchers have linked malignant hyperthermia

susceptibility to chromosome 19 between markers D19S9 and APOC2. Genes located within this region are considered

to be candidates for the elusive, defective “gene” for malignant hyperthermia. Markers identified with a D and

followed by a sequence of numbers and letters have not yet been identified as part of a known gene sequence. Adapted

with permission from Levitt RC, McKusick VA, Fletcher JE, Rosenberg H. Nature. 1990;345:298. Letter.

MHS: malignant hyperthermia susceptibility

GPI: glucose phosphate isomerase

MAG: myelin-associated glycoprotein

RYDR: ryanodine receptor

CYP2A: cytochrome P450, subfamily 11A

LIPE: hormone-sensitive lipase

CEA: carcino-embryonic antigen

PSBG1: pregnancy-specific B-1-glycoprotein 1

ATP1A3: ATPase; Na+, K+, a3 polypeptide

APOC2: apolipoprotein C-11

CKMM: creatine kinase, skeletal muscle

DM: dystrophia myotonica
Anesthesia and Perioperative Care of the Combat Casualty

826

Single-Point Mutation of Ryanodine-Receptor

Gene

The second breakthrough in the genetics of malignant hyperthermia was reported in 1991. This

research identified a single-point mutation of the

porcine ryanodine-receptor gene, which results in

the substitution of a cysteine for an arginine at

position 615 in the ryanodine receptor of susceptible swine.61 The mutation was present in five of six

breeds and was present at the same frequency as

porcine stress syndrome for that breed. In the sixth

breed, Hampshire, porcine stress syndrome has not

been reported.

Using this information, another team of researchers examined 35 families whose members are susceptible to malignant hyperthermia for the corresponding human ryanodine gene mutation.62 In

one family, three members were identified as heterozygous for the substitution. Genetic identification of susceptibility was consistent with the results

of prior halothane and caffeine contracture testing.

This family was originally identified when the

proband exhibited masseter muscle spasm after the

administration of succinylcholine. Although the

study identifies a common defect in porcine and

human malignant hyperthermia, it also indirectly

indicates genetic heterogeneity in human malignant hyperthermia.

The most convincing data supporting genetic

heterogeneity in human malignant hyperthermia were

provided in 1991.37 In three susceptible families,

linkage measurements were calculated for the

ryanodine receptor gene, CYP2A, and several other

markers in the area of 19q12-13.2. Malignant hyperthermia susceptibility did not cosegregate with any of

the previously identified markers or genes. Although

linkage for the human lipase gene was not calculated

in this report, it can also be eliminated as a candidate

gene in these families, because the human lipase gene

is flanked on both sides by markers that were tested

for linkage. Even though the data do not identify a

new site for the malignant hyperthermia defect in

these families, they support the evidence for at least

one additional genetic locus for the syndrome.

Advances in the pathophysiology of malignant

hyperthermia will continue to rely on the application of genetic analysis to families whose susceptibility has been delineated through halothane and

caffeine contracture testing. Likewise, animal models will continue to be invaluable in the search for

other causes of malignant hyperthermia. If porcine

malignant hyperthermia proves to be a homogeneous defect, the model may only apply to a small

percentage of humans susceptible to the syndrome.

Perhaps other models (canine, equine, goat) will

provide new clues to explain the clinical syndrome

of human malignant hyperthermia.

EVALUATION OF SUSCEPTIBILITY

cause the muscle must remain viable throughout

the testing period (tests must be completed within

5 h of the biopsy) and cannot be preserved or frozen.

Only 12 medical centers in North America provide

diagnostic contracture testing. Tests that show

some promise for the future include genetic analysis64 and phosphorus nuclear magnetic resonance

spectroscopy.64,65 Although further development of

these tests is necessary, they provide hope for a

simpler and more accurate diagnostic test in the

future.

Physical findings that have been associated with

malignant hyperthermia include increased muscle

bulk, hyperextensible joints, strabismus, and

scoliosis. Rare diseases such as Duchenne and

Becker type muscular dystrophies, myotonia

congenita, central core disease, King-Denborough

syndrome, Schwartz-Jampal syndrome and osteogenesis imperfecta have been linked to malignant

hyperthermia, but these are highly unlikely to be

seen on the battlefield. A history of muscle cramps

No simple screening test or minimally invasive

diagnostic test exists to identify patients susceptible to malignant hyperthermia. Although physical examination can identify loosely associated abnormalities that are common in the general

population, the syndrome lacks a distinct physical

sign to identify susceptible patients. Numerous

tests have tried to identify susceptible patients.

These include serum creatine kinase, serum cholinesterase levels, chemiluminescence, human leukocyte antigen, platelet nucleotide depletion test,

erythrocyte fragility, and the calcium uptake test in

muscle. While some of these tests may be useful

under restricted conditions, they have not been

successful when applied to a larger population of

patients. The only tests that reliably identify patients who have exhibited the clinical syndrome are

the halothane and caffeine contracture tests.63 However, these tests require not only a skeletal muscle

biopsy, they also require the biopsy to be performed

at a malignant hyperthermia diagnostic center be-
Malignant Hyperthermia

827

Fig. 29-4. This tracing illustrates an abnormal contracture

response of human skeletal muscle to 3% halothane. A

strip of muscle (2–3 cm, 100–200 mg) is tied with silk

thread at both ends. One end is attached to a hook in the

tissue bath, while the other is attached to a strain-gauge

transducer. The muscle strip is submerged in Krebs solution and oxygenated via a sintered disk with a mixture of

95% oxygen and 5% carbon dioxide. Transmural electrical stimulation is applied to the muscle strip via platinum

electrodes. The muscle is electrically stimulated for a

minimum of 15 minutes, or until a stable baseline tension

is obtained. A twitch height of greater than 0.5 g tension

to the electrical stimulation is considered viable for testing. Halothane is delivered to the tissue bath by adding

it to the mixture of oxygen and carbon dioxide. A response is considered positive when baseline tension increases by greater than 0.7 g within 10 minutes of exposure to 3% halothane. A normal skeletal muscle response

to halothane is an increase in twitch tension height without an increase in baseline tension. Reprinted with permission from Muldoon SM, Karan SM. Hyperthermia

and hypothermia. In: Rogers MC, Tinker JH, Covino BG,

Longnecker DE, eds. Principles and Practice of Anesthesiology. St Louis, Mo: Mosby–Year Book; 1993: 2508.

1 11 3 5 7 9 13 15 17 19 21 23

1

3

5

7

9

3% Halothane

Tension (g)

Time (min)

or heat intolerance has no predictive value for the

occurrence of malignant hyperthermia.

The halothane and caffeine contracture tests are the

most widely accepted diagnostic tests for the identification or conformation of malignant hyperthermia

susceptibility; however, due to the constraints already discussed, these tests will not be available on (or

near) the battlefield. The response of skeletal muscle

to halothane is the most specific test for malignant

hyperthermia, but it is the least sensitive (Figure 29-4).

Caffeine will produce a contracture in any skeletal

muscle, but this response will occur at a lower dosage

in susceptible individuals. Besides requiring a biopsy

from the vastus lateralis muscle (3 cm • 1 cm), these

contracture tests have other drawbacks:

• They require a significant amount of technical expertise to perform.

• They are performed at only 12 sites in North

America.

• A diagnostic gray zone exists when the

muscle responds to halothane or caffeine

but not strongly enough to meet the positive requirements. By applying a wide spectrum of susceptibility, these patients are

usually identified as positive at the lower

end of the spectrum.

• At this time, false-positive results cannot

be identified because these patients will

not be exposed to triggering agents.

• Although no false-negative results have been

reported, few reports exist of patients with

negative contracture results and subsequent

exposure to triggering agents.66

Any soldier who exhibits the clinical syndrome does

not need contracture testing prior to future anesthetics, (eg, if further surgery were necessary before the

soldier could be discharged from the military).

Contracture testing is most useful in confirming

suspicious episodes and in helping to identify susceptible family members. Soldiers who have not

exhibited the clinical syndrome, but have been informed they may be susceptible, should be evaluated with contracture testing as soon as possible.

Malignant hyperthermia diagnostic evaluations can

be arranged for armed forces personnel or their

dependents by contacting the following address or

commercial telephone number:

Uniformed Services University of the Health

Sciences

Department of Anesthesiology

Director, Malignant Hyperthermia Diagnostic

Center

4301 Jones Bridge Road

Bethesda, Maryland 20814-4799

Telephone: (301) 295-3140
Anesthesia and Perioperative Care of the Combat Casualty

828

SUMMARY

Malignant hyperthermia is a rare pharmacogenetic disease that can be expressed on exposure to

triggering anesthetic agents. No simple, widely

applied test exists to screen for susceptible individuals. The hypermetabolic syndrome is identified by increases in carbon dioxide production,

lactic acid production, muscle rigidity, and sympathetic tone. Temperature elevation is a late

sign. Treatment consists of prompt recognition

of the clinical syndrome, removal of the triggering agents, rapid administration of dantrolene,

and supportive care. Successful management of

malignant hyperthermia is possible, even in austere conditions, when treatment plans are formulated in advance and are tailored to the resources

available.

1. Muldoon SM, Karan SM. Hyperthermia and hypothermia. In: Principles and Practice of Anesthesiology. Rogers M,

Tinker J, Covino B, Longnecker D, eds. St Louis, Mo: Mosby–Year Book; 1993: 2499–2520.

2. Gronert GA, Schulman SR, Mott J. Malignant hyperthermia. In: Miller R, ed. Anesthesia. New York, NY:

Churchill, Livingstone; 1990: 935–956.

3. Rosenberg H, Seitman D. Pharmacogenetics. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical Anesthesia.

Philadelphia, Pa: JB Lippincott; 1989: 459–472.

4. Ellis FR, Halsall PJ, Christian AS. Clinical presentation of suspected malignant hyperthermia during anaesthesia

in 402 probands. Anaesthesia. 1990;45:838–841.

5. Gronert GA, Ahern CP, Milde JH. Treatment of porcine malignant hyperthermia: Lactate gradient from muscle

to blood. Can Anaesth Soc J. 1986;33:729–736.

6. Gronert GA, Theye RA. Halothane-induced porcine malignant hyperthermia: Metabolic and hemodynamic

changes. Anesthesiology. 1976;44:36–43.

7. Britt BA, Kalow W. Malignant hyperthermia: A statistical review. Can Anaesth Soc J. 1970;17:293–315.

8. Harrison GG. Porcine malignant hyperthermia. In: Britt BA, ed. Int Anesthesiol Clin: Malignant Hyperthermia.

1978:17:25–61.

9. Mathieu A, Bogosian AJ, Ryan JF. Recrudescence after survival of an initial episode of malignant hyperthermia.

Anesthesiology. 1979;51:454–455.

10. Littleford JA, Patel LR, Bose D. Masseter muscle spasm in children: Implications of continuing the triggering

anesthetic. Anesth Analg. 1991;72:151–160.

11. Delphin E, Jackson D, Rothstein P. Use of succinylcholine during elective pediatric anesthesia should be

reevaluated. Anesth Analg. 1987;66:1190–1192.

12. Rosenberg H, Shutack JG. Masseter muscle spasm in children. Anesth Analg. 1991;73:361–362. Letter.

13. Patel LR, Littleford JA. Masseter muscle spasm in children. Anesth Analg. 1991;73:362–363. Reply to letter.

14. van der Spek AF. Triggering agents continued after masseter spasm: There is proof in this pudding! Anesth

Analg. 1991;73:364–365.

15. Carroll JB. Increased incidence of masseter spasm in children with strabismus anesthetized with halothane and

succinylcholine. Anesthesiology. 1987;67:559–561.

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Malignant Hyperthermia

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384.

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24. Grinberg R, Edelist G, Gordon A. Postoperative malignant hyperthermia episodes in patients who received

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27. Harrison GG. Dantrolene—dynamics and kinetics. Br J Anaesth. 1988;60:279–286.

28. Rubin AS, Zablocki AD. Hyperkalemia, verapamil, and dantrolene. Anesthesiology. 1987;66:246–249.

29. Saltzman LS, Kates RA, Corke BC. Hyperkalemia and cardiovascular collapse after verapamil and dantrolene

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30. Wasserman K, Hansen JE, Sue DY. Facilitation of oxygen consumption by lactic acidosis during exercise. NIPS.

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31. Beebe JJ, Sessler DI. Preparation of anesthesia machines for patients susceptible to malignant hyperthermia.

Anesthesiology. 1988;69:395–400.

32. Ording H. Incidence of malignant hyperthermia in Denmark. Anesth Analg. 1985;64:700–704.

33. Ellis FR, Halsall PJ. Malignant hyperpyrexia. Br J Hosp Med. 1980;24:318–327.

34. Denborough MA, Lovell RH. Anesthesia deaths in a family. Lancet. 1960;2:45.

35. McPherson EW, Taylor CA. The genetics of malignant hyperthermia: evidence for heterogeneity. Am J Med

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36. Nelson TE, Flewellen EH, Gloyna DF. Spectrum of susceptibility to malignant hyperthermia—diagnostic

dilemma. Anesth Analg. 1983;62:545–552.

37. Levitt RC, Nouri N, Jedlicka AE. Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.

Genomics. 1991;11:543–547.

38. Gronert GA, Milde JH, Theye RA. Role of sympathetic activity in porcine malignant hyperthermia. Anesthesiology. 1977;47:411–415.

39. Berman MC, Harrison HH, Bull AB. Changes underlining halothane-induced malignant hyperpyrexia in

Landrace pigs. Nature. 1970;225:653–655.

40. Ellis FR, Harriman DG, Keaney NP. Halothane-induced muscle contracture as a cause of hyperpyrexia. Br J

Anaesth. 1971;43:721–722.

41. Satnick JH. Hyperthermia under anesthesia with regional muscle flaccidity. Anesthesiology. 1969;30:472–474.

42. Endo M. Calcium release from the sarcoplasmic reticulum. Physiol Rev. 1977;57:71–108.

43. Lai FA, Meissner G. The muscle ryanodine receptor and its intrinsic Ca2+ channel activity. J Bioenerg Biomembr.

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44. Kalow W, Britt BA, Terreau ME. Metabolic error of muscle metabolism after recovery from malignant

hyperthermia. Lancet. 1970;2:895–898.

45. Weber A. The mechanism of action of caffeine on sarcoplasmic reticulum. J Gen Physiol. 1968;52:760–772.

46. Iaizzo PA, Klein W, Lehmann-Horne F. Fura-2 detected myoplasmic calcium and its correlation with contracture

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653.

47. Lopez JR, Alamo L, Jones DE. Ca2+ in muscles of malignant hyperthermia susceptible pigs determined in vivo

with Ca2+ selective microelectrodes. Muscle Nerve. 1986;9:85–86.

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49. Ohnishi ST. Calcium-induced calcium release from fragmented sarcoplasmic reticulum. J Biochem. 1979;86:1147–

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51. Meissner G. Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. J Biol

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52. Nelson TE, Sweo T. Ca2+ uptake and Ca2+ release by skeletal muscle sarcoplasmic reticulum: Differing

sensitivity to inhalational anesthetics. Anesthesiology. 1988;69:571–577.

53. Ohta T, Endo M. Ca-induced Ca-release in malignant hyperthermia susceptible pig skeletal muscle. Am J Physiol.

1989;256:C358–367.

54. Mickelson JR, Gallant EM, Litterer LA. Abnormal sarcoplasmic reticulum receptor in malignant hyperthermia.

J Biol Chem. 1988;263:9310–9315.

55. Ervasti JM, Mickelson JM, Louis CF. Transverse tubule calcium regulation in malignant hyperthermia. Arch

Biochem Biophys. 1989;269:497–506.
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56. Levitt RC, McKusick VA, Fletcher JE. Gene candidate. Nature. 1990;345:297–298. Letter.

57. Cheah KS, Cheah AM. Skeletal muscle mitochondrial phospholipase A2 and the interaction of mitochondria and

sarcoplasmic reticulum in porcine malignant hyperthermia. Biochim Biophysica Acta. 1981;638:40–49.

58. Foster PS, Gesini E, Claudianos C. Inositol 1,4,5,-triphosphate phosphatase deficiency and malignant hyperpyrexia

in swine. Lancet. 1989;2:124–127.

59. McCarthy TV, Healy JM, Heffron JJ. Localization of the malignant hyperthermia susceptibility locus to human

chromosome 19q12-13.2. Nature. 1990;343:562–564.

60. MacLennan DH, Duff C, Zorzato F. Ryanodine receptor gene is a candidate for predisposition to malignant

hyperthermia. Nature. 1990;343:559–561.

61. Fujii J, Otsu K, Zorzato F. Identification of a mutation in porcine ryanodine receptor associated with malignant

hyperthermia. Science. 1991;253:448–451.

62. Gillard EF, Otsu K, Fujii J. A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially

causative of human malignant hyperthermia. Genomics. 1991;11:751–755.

63. Larch MG, and the North American Malignant Hyperthermia Group. Standardization of the caffeine halothane

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64. Olgin J, Rosenberg H, Allen G. A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic

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65. Olgin J, Zohar A, Rosenberg H. Non-invasive evaluations of malignant hyperthermia susceptibility with

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Anesthesia for Casualties of Chemical Warfare Agents

833

Chapter 30

ANESTHESIA FOR CASUALTIES OF

CHEMICAL WARFARE AGENTS

DAVID J. BAKER, M. PHIL., D.M., FFARCS*; AND J. M. RUSTICK, M.D.†

INTRODUCTION

ASPECTS OF TOXIC AGENTS OF IMPORTANCE IN MILITARY ANESTHESIA

The Spectrum of Toxic Hazards in Warfare

Characteristics of Toxic Agents

PROTECTION, DETECTION, AND DECONTAMINATION

SITES OF INJURY BY TOXIC AGENTS

The Skin and Viscera

The Central and Peripheral Nervous Systems and the Eyes

The Respiratory Tract

MANAGEMENT OF ANESTHESIA AFTER TOXIC INJURY

Types of Casualties

Triage of Casualties

Casualty-Management Phases

Preoperative Assessment and Examination

Anesthetic Induction, Maintenance, and Recovery

TOXIC AGENT COMPLICATIONS OF MILITARY ANESTHESIA

Respiratory Complications

Neurological Complications

Nondepolarizing Neuromuscular Blocking Agents in Organophosphate

Poisoning

PYRIDOSTIGMINE PRETREATMENT AND GENERAL ANESTHESIA

Pharmacology

Premedication

Induction Agents

Neuromuscular Blocking Agents

Action of Pretreatment on Depolarization Block

Action of Pyridostigmine on Nondepolarizing Agents

Effect of Pretreatment on Neuromuscular Monitoring

Inhalation Anesthetics

Military Clinical Experience

SUMMARY

*Department of Clinical Neurological Sciences, University of Southampton, United Kingdom

†Director of Military Medical Research, Public Safety Group, 12608-B Lakeridge Drive, Woodbridge, Virginia 22192
Anesthesia and Perioperative Care of the Combat Casualty

834

INTRODUCTION

Chemical agents (ie, substances intended for use

in military operations to kill, seriously injure, or

otherwise incapacitate through pathophysiological

effects1,2) were first used on a wide scale in modern

times during World War I. Although in recent years

the demise of the Warsaw Pact has markedly lessened the threat of a major war fought with unconventional weapons, the same cannot be said for

what may happen in the Third World. In fact, there

is evidence that chemical agents have been used in

at least seven military actions since 1965 (Exhibit 30-

1). While the list of chemical warfare agents most

likely to proliferate is not especially long (Exhibit

30-2), there is nothing to say that a country seeking

to develop a surreptitious chemical warfare capability may not use a nontraditional agent as a

weapon. Even traditional agents may be used in a

nontraditional manner. An excellent example of

this is Iraq’s use of the mixture of GB (sarin) and GF

(this agent does not have a common name), which

together pose a threat via both the respiratory and

the transdermal routes of exposure. As treaties

banning the use of chemical warfare agents become

more numerous, the more likely we are to encounter the unexpected.

The trauma anesthesia provider is usually concerned with the management of casualties injured

by physical forces such as blunt and penetrating

injury and blast.3 The American College of Surgeons’ standard Advanced Trauma Life Support

(ATLS) teaching4 is geared to rapid assessment and

management of such casualties of conventional

warfare. The concept of injury from chemical agents,

however, extends the notion of trauma into a new

and often more difficult area, where the injury may

not always be immediately obvious and may also

still be developing during the period of initial assessment. Since the risk of injury from chemical

agents in warfare has not diminished in recent years,

the military anesthesia provider must always be

prepared for the possibility that casualties might

suffer from chemical as well as from physical trauma.

To a certain extent, the existence of thermal injury in

warfare, an injury so very different from the much

more common ballistic trauma that has historically

dominated warfare, serves to remind us of the need

to be prepared to treat unusual injuries. The absence of chemical casualties in World War II and

subsequent actions where North Atlantic Treaty

EXHIBIT 30-1

ALLEGED USES OF CHEMICAL

WARFARE AGENTS IN THIRD-WORLD

COUNTRIES BEFORE THE PERSIAN

GULF WAR

Egypt in South Yemen in 1963–1968

Vietnam in Laos, 1975–1978

Ethiopia against Eritrean and Somalia-backed

rebels, 1976– ?

Vietnam in Cambodia, 1978– ?

China and Vietnam, 1979

Iraq against Iran, 1984–1988

Iraq against the Kurds, 1988

EXHIBIT 30-2

CHEMICAL AGENTS MOST LIKELY TO

BE PROLIFERATED

Nerve Agents

GA: Tabun

GB: Sarin

GF: (no common name)

GB/GF Mixture

Vesicant Agents

HD: Sulfur mustard

Choking Agents

CG: Phosgene

Blood Agents

AC: Hydrogen cyanide

Incapacitating Agents

BZ: (no common name)

Vomiting and Riot Control Agents

DM: Adamsite

CS: Tear gas
Anesthesia for Casualties of Chemical Warfare Agents

835

Organization forces were involved has perhaps induced a false sense of security. However, there

have been other wars in which chemical weapons

have been used with devastating effect.5–7 Fears

during the Persian Gulf War (1990–1991) highlighted

real problems posed by the threat of chemical weapons and enforced new thinking about management

of chemical casualties. This was particularly true

for anesthesia, and at the time of writing there is

again an increased awareness among military medical officers of the potential problems.8

The nature of chemical weapons and the formal

management of chemical casualties are discussed in

Medical Aspects of Chemical and Biological Warfare, a

volume of the Textbook of Military Medicine series,

and will not be further discussed here except to

mention that the two main chemical threats are

• nerve agents, which kill by causing respiratory paralysis due to their irreversible inhibition of acetylcholinesterase, with consequent accumulation of acetylcholine in

nicotinic and muscarinic receptors, and

• vesicants, of which the sulfur mustards are

best known, and which incapacitate by causing second-degree chemical burns of the

skin.

This chapter covers some of the particular problems posed to military anesthesia providers by the

management of the chemical injury itself and by

surgical anesthesia for trauma casualties who may

also have been exposed to chemical agents. With

the ever-increasing number of agents now regarded as potential threats, the approach will be to look

at the injury primarily from a pathophysiological standpoint rather than from that of agent specificity.

In general, the involvement of the military anesthesia provider will focus on three broad categories

of casualties:

1. those with potentially fatal exposure to a

chemical agent, who need immediate, lifesaving airway management but who will

not require a general anesthetic;

2. those with combined ballistic and chemical agent injuries, who will require anesthesia for the management of the conventional injury; and

3. those who have received pyridostigmine

prophylaxis against chemical agents, and

who will also require anesthesia for the

management of a conventional injury.

Chemical injury may affect almost all the systems of the body but particularly the respiratory

and nervous systems. Military anesthesia providers may be directly concerned with these in all

stages of management of the wounded, including

resuscitation, preoperative stabilization, perioperative and postoperative care, intensive care, and

recovery. Chemical injury can affect all these stages,

creating clinical problems in their own right and

complicating conventional management of injuries

that require surgery. Anesthesiologists, as a result

of their training, are well placed to grasp the clinical

problems arising from chemical injury. The pharmacology and toxicology of the agents will be familiar, as will the nature of the neuromuscular

paralysis and respiratory complications such as

pulmonary edema and respiratory distress syndrome, which are the life-threatening aspects of

chemical injury.

Conventional teaching of chemical warfare injury has often tended to view the subject in isolation. No doubt based on the initial use of poison gas

in 1915, the use of chemical arms is often viewed as

a special event that will create mass casualties from

only one cause. This ignores the subsequent use of

poison gas in World War I, wherein the gas was

usually disseminated from shells fired in conjunction with conventional high-explosive shells. Thus,

casualties with combined ballistic and chemical injuries occurred. Exactly how common such casualties were in World War I is not known. However, of

the 546 American soldiers who died following exposure to gas in the period March to November

1918, 6% also had ballistic injuries.9 Given the

tactical doctrine of chemical agent powers such as

the former Soviet Union, which took an integrated

approach to the use of chemical weapons (seeing

them as part of the ordinary armamentarium available to field commanders, as opposed to being special “weapons of mass destruction”), combined ballistic and chemical casualties should be expected

whenever chemical weapons are used.10 During the

Iran–Iraq War, when chemical agents were used the

most extensively since World War I (Exhibit 30-3),

chemical weapons were also used in a localized,

tactical way, particularly as part of defensive infantry actions. The consequence of these developments is that wounding by chemical agents should

not be viewed in isolation. It may now be appropriate to think of wounding in three main classes:

1. conventional traumatic wounding, where

the tissues are disrupted by externally impressed forces;
Anesthesia and Perioperative Care of the Combat Casualty

836

EXHIBIT 30-3

IRANIAN EXPERIENCE WITH CHEMICAL WARFARE AGENTS

During the Iran-Iraq War, modern medicine was applied to the treatment of injuries caused by sulfur

mustard, tabun, Lewisite, and the biological agent mycotoxin.1,2 Although data are limited, there are a number

of lessons that we should note. The most unexpected was the surprisingly low mortality: fewer than 1% of the

estimated 27,000 Iranian chemical casualties.3

Troops with organophosphate exposure fell into four categories. Those with the greatest exposure died in

the field. The number appears to have been very small even though most of the Iraqi attacks were made against

unprotected Iranian troops. Those most severely injured who reached medical aid were unconscious and

unresponsive, and often in respiratory arrest. The seriously intoxicated had symptoms of dizziness, disorientation, anxiety, salivation, and respiratory difficulty. Those with relatively mild symptoms were often

physically difficult to manage because of their disorientation. By far the largest number of casualties required

no treatment other than decontamination.

Treatment of mustard exposure during the Iran-Iraq War reflects the experience gained in the management

of burn wounds during the 80 years since World War I. Treatment begins with early and thorough decontamination. Early in the course of injury, blistering may not be present. Still, removal of contaminated clothing is

important to limit the casualty’s contact time with the agent. Shaving of the affected areas followed by washing

mechanically removes and dilutes the agent. Aspiration of blisters, removal of necrotic tissue, and treatment

of the skin lesions with silver sulfadiazine cream forms the basis for treatment of skin injury. Respiratory

exposure to mustard creates its own set of problems. Depending on the degree of injury, the treatment must be

adjusted to the degree of injury. Humidified air or oxygen helps to prevent airway obstruction. Bronchodilators,

mucolytics, and expectorants are useful. In cases of serious injury, mechanical ventilation with positive endexpiratory pressure and acid–base balance control are used to support the casualty until the injuries resolve.

Injury to the eyes is treated with irrigation and sodium sulymid. Pain is treated with systemic medications.

Because of weight loss, often in excess of 10 kg, nutritional support is instituted to help reduce the significant

mortality associated with negative nitrogen balance. Once the patient reaches a setting for definitive care,

therapy is divided into two parts: a general supportive treatment for sepsis and dehydration, and treatment to

eliminate toxins from the body.1

Significant observations from the Iran-Iraq War include the following:

• Decontamination, using soap and water and shaving body hair, was done early. This protected

medical personnel and simplified further treatment.

• Comatose casualties of nerve agents who did not have cardiovascular problems were treated with

large doses of atropine, 50 to 200 mg administered intravenously. Most casualties received 2 mg every

8 hours. Comatose casualties with significant cardiovascular deterioration (such as bradycardia after

2 mg of intravenous atropine) were most often found not to survive.

• Mustard, although it dates from World War I, continues to be an important chemical agent. It is a

vesicant but also has effects on multiple organ systems.

(1) Colardyn F, de Keyser H, Ringoir S, de Bersaques J. Clinical observation and therapy of injuries with vesicants. Journal

de Toxicologie Clinique et Experimentale. 1986;6(4):237–246. (2) Kadivar H, Adams SC. Treatment of chemical and biological

warfare injuries: Insights derived from the 1984 Iraqi attack on Majnoon Island. Milit Med. 1991;156:171–177. (3) Hammick

M. All stick and no carrot. International Defense Review. 1991;(Dec):1323–1327.

2. toxic wounding, where the body systems

are poisoned; and

3. environmental wounding, where the

body is damaged by excesses of heat and

cold.

Casualties may occur from any combination of all

three categories.

In a mixed chemical and conventional environment, the number of casualties with combined (both

conventional penetrating and chemical) wounds

could be considerable. Not only will these numbers

cause potential problems for military anesthesia

providers, but other aspects of combat casualty care

will also be affected. One study11 used the U.S.

Marine Surgical Data Base from the Vietnam War to

calculate a figure of potential protective mask failures secondary to conventional wounds of the head
Anesthesia for Casualties of Chemical Warfare Agents

837

and neck (including the trachea, oral cavity, etc).

These researchers predicted that 34% of casualties

presenting at a hospital would have wounds that

interfered with proper sealing of fielded gas masks.

Since this study makes no attempt to consider

wounds that would disrupt other components of

mission-oriented protective posture (MOPP) gear,

34% may indeed be a conservative estimate.

ASPECTS OF TOXIC AGENTS OF IMPORTANCE IN MILITARY ANESTHESIA

feasible, and that their use as sophisticated chemical agents is more likely.12

The Spectrum of Toxic Hazards in Warfare

Medically, it is now desirable to integrate traditional definitions of chemical and biological agents

into a unified concept known as the chemical–biological warfare spectrum of toxic agents. This is

shown diagonally in Exhibit 30-4, where the agents

are arranged in order of ascending molecular weight,

with conventional chemical agents on the left and

the self-reproducing agents such as bacteria and

viruses on the right. Toxins and other agents of

biological origin occupy the middle.

The spectral, rather than the agent-specific, view

is important clinically because pathophysiological

mechanisms that should be considered in medical

management are common to agents from different

parts of the spectrum. Neuromuscular paralysis

and pulmonary edema are two examples. Failure of

the neuromuscular junction, for example, can be

caused by two agents as chemically different as a

nerve agent and botulinum toxin. The clinical result, however, is the same, and in severe cases the

primary lifesaving measure is artificial ventilation.

Similarly, there are many agents of which the end

result is pulmonary edema. The spectral concept is

a reminder to military anesthesia providers that

Recent changes in thinking about the status and

definition of toxic warfare agents are of particular

importance to military anesthesia providers.

Conventionally, riot control agents, herbicides,

smoke, and flame are excluded from the definition of chemical agents, although their clinical effects (ie, they kill, seriously injure, or otherwise

injure via their pathophysiological effects) bring

them within the classical definition of chemical

agents. Biological agents, on the other hand, are

defined as living organisms, the use of which is

intended to kill or incapacitate man in warfare.2

Under the 1972 Biological Warfare Convention, toxins, which originally could only be produced by

living organisms, were included with the biological

agents, despite the fact that they are, in fact, chemical substances with unusually high molecular

weights.

Although we could argue that all agents designed to incapacitate or kill are, by definition,

biological, since the target is man and not his machines, the traditional view of chemical and biological agents has persisted. Clinically, however, the

separation of chemical and biological weapons has

now become increasingly difficult: new technologies have expanded the number of potential agents

in both classes—particularly in the toxins, which lie

midway between the two. Developments in biotechnology mean that the synthesis of toxins is now

EXHIBIT 30-4

THE SPECTRUM OF CHEMICAL–BIOLOGICAL WARFARE AGENTS

Adapted with permission from Baker DJ. Chemical and biologic warfare. Part 2. In: Baker DJ. Extreme environmental

conditions. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St. Louis, Mo: Mosby–Year Book; 1993: Chap

108: 1331.

Low Molecular Weight High Molecular Weight

Nerve agents Neuropeptides Bacteria

Pulmonary irritants Toxins Viruses

Vesicants Rickettsiae

Cyanogens
Anesthesia and Perioperative Care of the Combat Casualty

838

medical management must respond to system dysfunction, not simply to etiology.

Characteristics of Toxic Agents

The characteristics of toxic agents may be divided into the operational and the pathophysiological. The operational aspects are not discussed in

this chapter. The pathophysiological aspects of

toxic agents are of particular importance to military

physicians, however, and include (a) toxicity,

(b) latency of onset, and (c) transmissibility.

Toxicity

Toxic agents can kill or incapacitate. The biological effects of potential agents may be estimated

from animal studies and data from accidental exposure, but there may be considerable difference from

one species to another. The clinical importance of

toxicological data is to give some idea of the substances’ hazards to man. There are a number of

ways of expressing toxicity of agents (Table 30-1);

the following are the most common:

• Ct is the product of the concentration of an

airborne agent multiplied by the time it

was inhaled, given a standard rate of respiration. The Ct product applies to the middle

range of exposure but is inaccurate at very

high or very low levels. The units of Ct are

mg • min/m3. The relationship of Ct to

absorbed dose is a function of the rate of

respiration or the total exposed skin area.

This should always be specified when quoting Ct values, and is conventionally accepted as 10 to 15 L/min.

• LCt50 and ICt50 are the Ct values for a

specified route of absorption that will kill

(lethal, L) or incapacitate (I) 50% of the

exposed population.

• LD50 and ID50 are the doses for a specified

route of absorption that will kill (L) or incapacitate (I) 50% of the exposed population.

Latency

Latency of action is a clinically important property of toxic agents. All agents have a latent period,

ranging from a few seconds in the case of cyanide

to several hours in the case of some vesicants. Biological agents such as Brucella can have a latent

period as long as 3 weeks. A patient presenting

with few symptoms after exposure may develop

more, and more dramatic, symptoms later. Because

of this, detecting the use of a toxic agent by

the immediate effects on those who have been exposed may not always be possible. Specific latency

may be modified by physical factors such as ambient temperature and the amount of exertion after

exposure. Latency often decreases as absorbed

dose increases.

TABLE 30-1

RELATIVE TOXICITIES OF SOME IMPORTANT BIOLOGICAL AND CHEMICAL WARFARE

AGENTS*

LCt50

Agent (mg•min/m3) LD50

Botulinum toxin† 0.15 μg/kg

Soman 40–60 0.025 mg/kg, IV

Sarin 70–100 0.01 mg/kg, IV

Tabun 150 0.08 mg/kg, IV

Cyanide 2,000–5,000 1.0 mg‡

Sulfur mustard 1,500 100.0 mg/kg

* Values are based on experimental and extrapolated data from accidential exposure. Toxicities are expressed as LCt50, the median

lethal exposure delivered by inhaling a concentration C for a time t in minutes; and LD50, the conventional median lethal dose.

†Estimated respiratory value for man

‡Respiratory value

Adapted with permission from Baker DJ. Chemical and biologic warfare. Part 2. In: Baker DJ. Extreme environmental conditions. In:

Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St. Louis, Mo: Mosby-Year Book; 1993: Chap 108: 1332.
Anesthesia for Casualties of Chemical Warfare Agents

839

Transmissibility

Toxic agents may affect not only the casualty but

also the casualty’s medical attendants. In the case

of biological agents, the risk of transmission by

infection is widely recognized. For chemical agents,

the risks are of contact and inhalational transmission to medical personnel if the casualty is not

properly decontaminated. Transmissibility is an

important characteristic that distinguishes toxic

from conventional weapons. All casualties of toxic

agents must always be regarded as risks to their

attendants, who may not themselves have been

involved in the original attack. This point has considerable significance for the operating theater team involved with the management of such casualties.

tamination—particularly where there is no direct

hazard from a liquid agent. Nevertheless, a surgeon who operates on a contaminated casualty risks

spreading contamination into the casualty, a very

bad practice indeed.

Although CPE offers greater freedom to work on

casualties contaminated with toxic agents, anesthesia providers should be aware of the limitations of

collective protection and the importance of careful

decontamination, and check the casualty’s contamination monitoring before entering the CPE. Experience from the 1991 Persian Gulf War emphasizes

the cramped conditions of anesthesia providers

working in CPE.8 The transit period for any patient

through the airlock system is particularly dangerous since it may not be physically possible for a

paramedical or anesthetic attendant to be present.

Toxic agents may be delivered as vapor, liquid,

or a particulate or liquid aerosol. The possibility

that chemical agents can be absorbed onto a carrier

dust that will deliver point concentrations of agent

directly to the alveoli is an ominous new development. For the anesthesia provider dealing with a

potentially contaminated patient, the risks are from

direct contact with liquid agent on the patient’s

clothing, from the vapor the liquid emits, and from

reaerosolization of powders.

The simplest method of detecting liquid agents

uses special detector papers (although the range of

agents detected is limited at this time). The most

useful technique for vapor analysis available for

use in the operating room is the chemical agent

monitor (CAM), which detects nerve and vesicant

chemical warfare agents and is used to identify the

presence of chemical agent vapors in decontamination operations. This device uses ion-cluster acceleration as the basis for analysis. This technique is

similar in principle to mass spectrometry but depends on forming hydrated ion clusters with the

toxic agent rather than on accelerating small ions.

In CAM, the vapor is sucked into a sampling port,

where a radioisotope is used to ionize the toxic

agent to form the ion clusters. These are then

Protection against chemical warfare agents and

their detection and decontamination are considered in detail elsewhere,1 but it is essential that

military anesthesia providers be familiar with these

concepts, as they affect field anesthetic practice in

many ways.

It is the policy of the U.S. military not to perform

surgery in a contaminated environment. The casualty should be adequately decontaminated before

being taken into the preoperative area or operating

room. Clothing should be removed, and the skin

and hair decontaminated with hypochlorite. A

casualty should not enter the “clean” operating

room or the collective protective ensemble (CPE)

until decontamination is accomplished; once this is

done, the danger from contamination is nil.

Although the desired aim of field anesthesia is to

work either on decontaminated casualties or in some

form of CPE, it may be necessary in extreme circumstances for hospital-based anesthesia providers to

work in an individual protective ensemble (IPE,

which is the British equivalent of MOPP gear), particularly in the early stages of resuscitation and

triage. Since individual protection involves isolating the operator from the contaminated environment by means of a protective suit and respirator, it

follows that many of the normal tactile skills available to the anesthesia provider will be lost or severely impaired, particularly since the casualty may

also be similarly isolated. In full MOPP gear, even

assessing for something so simple as the casualty’s

color will be difficult. Simple pulse measurement

may not be possible, although radial pulses are

palpable through an Mk 4 suit (ie, a kind of IPE)

when inner gloves are left out of the operator’s

ensemble (—DJB, personal observation, 1990).

It is clear that only the simplest lifesaving measures are available to the military anesthesia provider in full MOPP gear, although these must include definitive securing of the airway. If necessary,

it may be necessary to break the casualty’s own IPE

to gain access since the danger of airway obstruction outweighs the consequences of further conPROTECTION, DETECTION, AND DECONTAMINATION
Anesthesia and Perioperative Care of the Combat Casualty

840

accelerated down a high-voltage drift tube and the

collected current characteristics are analyzed at one

end. In its original form, CAM could be preset to

detect either mustard or nerve agent. A modification allows detection of several other agents, all of

which can be detected using the drift-tube technique. CAM may be used preoperatively to check

the decontamination of patients. One problem that

may arise is the slow clearance time of the instrument when background levels of agent are high.

Individual chemical agent detectors (ICAD), worn

by individual medical personnel, may provide the

earliest warning while contaminated patients are

being handled. The ICAD will identify nerve, blister, blood, and choking agents and will warn by

audio and visual alarms.

The possibility that chemical agents are absorbed

onto dusts, or that toxins are delivered as solid aerosols, should be considered with the greatest care. The

presence of dust on a patient should be treated with

suspicion, particularly since there is no simple toxindetection device available and these agents are likely

to be delivered in solid aerosol form.

If liquid agent is on a casualty, careful decontamination is required. There are two main methods, wet and dry. Wet decontamination involves

the use of oxidizing solutions containing hypochlorite, which effectively oxidizes liquid agents such as

mustard and nerve agents. Thickened nerve agents

such as thickened GD may have a consistency similar to that of glue and require scraping off before

decontamination can proceed further. Dry decontamination (which is not currently used by U.S.

forces) uses fuller’s earth, an absorbent clay, to

remove liquid agent. It should be understood that

absorption and removal of the chemical agent does

not decrease the agent’s toxicity, so care must be

taken with the discarded material. Fuller’s earth is

available in puffer bottles and impregnated pads

that may be applied directly to the contamination.

The proper sequence of decontamination consists

of first removing clothing, then decontaminating

the skin. Following decontamination, it is essential

that the patient be monitored carefully to allow

further medical intervention. An important point is

that in serious toxic injury, the normal ATLS processes should be dynamically integrated with the

decontamination processes. Proper assessment and

definitive airway management will be difficult until decontamination has been achieved.

SITES OF INJURY BY TOXIC AGENTS

than simply as a pattern of injury from a specific

agent.

The Skin and Viscera

The skin may be affected by vesicants and toxins.

Many agents acting on the skin exhibit considerable

latency. Although damage to the skin may be classed

as incapacitating rather than life-threatening, the

agents concerned, if inhaled, may have additional

serious effects on the respiratory tract. Therefore,

during assessment, skin lesions should be regarded

as a warning of possible accompanying respiratory

damage. Sulfur mustard was the vesicant most

widely used in World War I. Much clinical experience was gained at the time, but since then, there

have been only isolated case reports in which the

effectiveness of modern medical therapy can be

assessed (see Exhibit 30-1).14

The viscera may be affected by vesicants if ingested, and by nerve agents following local or systemic poisoning. Ingestion of nerve agents will

produce particularly marked intestinal actions,

which are probably of central nervous system origin rather than due to local cholinergic action.

In traumatic injury, the mechanism of injury may

be known and often will be a useful predictor of the

damage.13 Similarly, the knowledge that a toxic

injury has been caused by a particular agent (eg, an

organophosphate) will alert the anesthesia provider

to a specific pattern of damage. Knowledge of the

nature of the toxic agent is more important than

knowledge of the nature of a traumatic force; however, although information may be available at primary casualty assessment, it cannot be guaranteed.

Casualties with immediately life-threatening conditions such as apnea or cardiac arrest should receive immediate treatment before decontamination.

Decontamination typically takes 10 to 15 minutes,

but death from respiratory failure due to exposure

to nerve agents can occur within 5 minutes of exposure. In fact, respiratory support must begin before

the casualty is brought to the hospital—or to the

battalion aid station, for that matter. The casualty

will not wait until he arrives at the medical facility

to stop breathing. Nevertheless, excluding lifethreatening emergencies due to exposure to chemical agents, it is helpful to classify toxic injury in

terms of the damage that may be caused by a range

of different agents at key anatomical sites rather
Anesthesia for Casualties of Chemical Warfare Agents

841

The Central and Peripheral Nervous Systems

and the Eyes

The central nervous system is affected by a wide

range of agents including nerve agents and toxic

neuropeptides. Central nervous system symptoms

following nerve agent intoxication will be accompanied by peripheral nervous system symptoms in

both the voluntary and autonomic systems. Symptoms caused by neurotoxins, however, may be varied, ranging from modification of thought processes

and mild delusions to frank coma. A careful assessment of the casualty’s level of consciousness is

therefore of great importance in the assessment of

any toxic casualty. Again, the latency periods will

be variable and observation over a lengthy period

may be required. At the level of the brainstem, the

central nervous system is affected by nerve agents

that produce central respiratory failure, and also by

cyanogen agents.

Paralysis caused by nerve agents is accompanied

by other signs of poisoning (eg, miosis, excessive

secretions), and the differential diagnosis from other

types of paralysis such as that caused by neurotoxins is not difficult. Paralysis is accompanied by

apnea, so an unventilated patient with paralysis is

unlikely to be seen at the hospital level. Paralysis

from nerve agents lasts 2 to 3 hours at most and

should not be confused with the more prolonged

paralysis caused by other agents such as botulinum

toxin.

The peripheral motor and autonomic nerves

are the sites of action of nerve agents and neurotoxins. Neuromuscular paralysis will therefore require differential diagnosis among several possible

causes both prejunctional and postjunctional. This

may be facilitated by the use of nerve stimulation

techniques, which are discussed later in this

chapter.

Vesicant agents cause damage to the eye and loss

of vision by blepharospasm and corneal ulceration.

Nerve agents may produce a variable loss of visual

acuity due to miosis and central nervous system

effects on the visual pathway. Loss of accommodation follows spasm of the ciliary muscle.

The Respiratory Tract

Toxic agents may seriously affect all stages of

respiration (Table 30-2). In toxic injury, the respiratory tract is particularly vulnerable and its management must take a high priority. Careful clinical

examination is of vital importance. While examinations such as radiography and blood gas analyses

may be available, simple clinical examination will

reveal much of value and must be undertaken as

soon as the patient is decontaminated and out of

MOPP gear. Five important points to remember are

the following:

1. The presence of burns on the skin may

indicate similar lesions within the respiratory tract.

2. The casualty’s color and the nature of the

respirations may point to impending respiratory failure.

3. The presence of paradoxical respiratory

movements may indicate upper respiratory blockage of large and small airways.

4. The presence of rales at the bases of the

lungs will indicate the development of pulmonary edema.

5. The presence of pathological amounts of

secretions in the airway in a casualty who

is likely to have been exposed to a nerve

agent is strong evidence that too little atropine has been given.

Certain toxins as well as inhaled vesicants have

particularly short latency periods, but the latency of

onset of symptoms in the chest after toxic injury

may be very variable. Any casualty with a suspected respiratory injury should be admitted to a

hospital for a mandatory 24-hour observation, during which the respiratory tract should regularly be

assessed for the development of signs.

MANAGEMENT OF ANESTHESIA AFTER TOXIC INJURY

The management of toxic casualties is an unfamiliar task for most anesthesiologists, but the specialty should be involved at the earliest stages of

planning of facilities to deal with the problem. Besides formulating plans to deal with mass or limited

casualties, planning must include flexibility for the

effects of unexpected chemical casualties on the

operation of a forward surgical facility. Although

intelligence may give good warning of a toxic attack, the information cannot be guaranteed, particularly in rapid-response operations. All ordinary anesthetic and surgical procedures are

hampered by the chemical environment, either from

the results of an attack or simply from the threat of
Anesthesia and Perioperative Care of the Combat Casualty

842

TABLE 30-2

EFFECTS OF TOXIC AGENTS ON RESPIRATION

Respiratory

Component Effect Toxic Agent

Central Nervous System Depression of respiratory drive and Nerve agents, cyanide, neuropeptides

convulsions leading to apnea

Peripheral Nervous System Neuromuscular paralysis of respiratory Nerve agents, neurotoxins

muscles

Nasopharynx May become blocked by excess secretions Lung-damaging agents, nerve agents

Prodromal rhinitis and rhinorrhea Vesicants

Sneezing Early symptom of mustard

Larynx Irritation, laryngeal spasm Upper-respiratory irritant lungdamaging agents

Riot-control agents, particularly CS

and CR (tear gas)

Nerve agents (theoretical)

Large Airways Blocked by secretions Variety of agents

Blocked by inhaled vomitus Nerve agents

Sloughing of walls of trachea and main Mustard agents

bronchi, produces “pseudodiphtheritic”

membrane, serious cause of large

airway obstruction, leading to

bronchopheumonia and death

Small Airways Blocked by secretions

Cholinergic innervation affected; Nerve agents

bronchospasm (relieved by atropine)

Chemical bronchiolitis, followed by Mustard agents

serious bronchospasm

Alveoli Toxic pulmonary edema Variety of agents, especially lungdamaging agents (latency 6–24 h)

Vesicant agents, particularly if

inhaled at high ambient

temperatures1

1

Willems JL. Clinical management of mustard gas casualties. Annales Medicinae Militaris Belgicae. 1989;3(suppl)1–61:47, 51.

it, enforcing the use of IPE-MOPP. The planning

stage should therefore ensure that the possibility of

toxic attack is understood, that equipment is designed to be simple and straightforward in use, and

that medical and paramedical personnel are adequately trained.

When reviewed, experience in the Persian Gulf

War showed that a number of personnel discontinued the use of pyridostigmine without medical

advice.15 Had there been actual exposure to nerve

agents, these troops and their missions would have

been at risk. Anesthesiologists, particularly those

in forward areas, are among the most suitable medical personnel to educate the troops to the necessity

of using such pretreatment as pyridostigmine and

to allay fears with regard to potential side effects.

U.S. military doctrine does not have anesthesiologists or surgeons checking decontamination procedures. By doctrine, noncommissioned officers do

decontamination and watch casualties during that
Anesthesia for Casualties of Chemical Warfare Agents

843

procedure. The following are potential areas of

responsibility in the management of casualties from

toxic attack:

• managing casualty reception, including

checking of decontamination procedures,

particularly for casualties in severe respiratory and neuromuscular distress;

• preoperatively assessing the whole patient,

who may be suffering from both traumatic

and toxic injury;

• assessing the likely impact of prophylactic

measures (eg, pyridostigmine bromide),

toxic agents, and therapeutic measures on

the subsequent action of anesthetic drugs

and agents;

• providing advice to surgeons on the morbidity factors associated with the toxic injury in otherwise uncomplicated surgery;

• managing casualties perioperatively;

• managing postoperative complications,

which may be toxic, anesthetic, or surgical,

or any combination; and

• managing patients who require postoperative intensive care.

The importance of decontamination has been

emphasized previously. However, although decontamination is vital for the safety of casualties

and medical personnel alike, it must not be allowed

to interrupt the continuous process of resuscitation

and assessment during triage. Decontamination

and monitoring must at all times be dynamic and

integrated with primary and continuing medical

care. Initially, the casualty arriving at a surgical

facility may have to be managed by medical attendants wearing MOPP gear, but the aim should be to

get the casualty into CPE as soon as possible to

facilitate examination and initial treatment.

Types of Casualties

The following types of casualties may be anticipated following actions where chemical weapons

have been employed:

• traumatic casualties, uncontaminated with

chemical agents;

• traumatic casualties, contaminated;

• toxic casualties;

• iatrogenic toxic casualties, produced as a

result of the side effects of antidotes to toxic

agents;

• combined traumatic and toxic casualties;

• thermal stress casualties (these will usually

be suffering from heat stress as a result of

wearing MOPP gear, but hypothermia may

also occur); and

• psychological casualties (combat stress reaction may be common in toxic warfare).

Triage of Casualties

Triage of casualties with conventional traumatic

wounds is considered in detail in Chapter 1, Combat Trauma Overview. It is important, however, to

apply a system of triage to casualties affected solely

by chemical agents. The following is the authors’

suggestion (with the U.S. Army’s triage designations in parentheses):

• T1 (Priority I and Priority IA): the casualty

requires immediate lifesaving treatment.

This will almost certainly involve securing

the airway, starting intermittent positivepressure ventilation (IPPV), and continuing pharmacological measures such as atropine, oximes, and benzodiazepines for

nerve agent poisoning. Agents causing this

type of immediately life-threatening injury

will be nerve agents, lung-damaging agents

(ie, phosgene), cyanides, and toxins.

• T2 (Priority II): some delay in management

is possible. Respiration may be compromised by direct airway problems and by

developing neuromuscular paralysis but

not to the extent that immediate intervention is indicated. Placing the casualty in

this triage category may be influenced by

military intelligence about the toxic agent

used. If considerable latency of action is

likely (eg, with vesicants and some lungdamaging agents), close observation of the

casualty is indicated to look for signs of

developing vesication in the airway, and

pulmonary edema.

• T3 (Priority III): minimal effects from the

toxic agent. The casualty may be returned

to duty after a period of observation.

• T4 (Priority IV): expectant treatment category. Casualties will usually be placed in

this category because facilities available for

their medical care are limited (eg, longterm IPPV) in relation to the facilities needed for a larger number of less-seriously

injured casualties. Unlike traumatic

wounds, there are few toxic injuries in which
Anesthesia and Perioperative Care of the Combat Casualty

844

the acute phase cannot be managed in the

field given sufficient intensive care resources. However, some chemical injuries

(eg, extensive vesicant burns) will require

long-term hospitalization, which will not

be practical in a field hospital.

Casualty-Management Phases

The anesthesiologist who assesses casualties with

toxic injuries for surgery must be aware of the

preceding medical management, which should have

been documented on the casualty card accompanying the patient. The nature of the agent used, the

likely exposure time, pretreatment, and early

therapy are of importance. The following five phases

may be identified:

1. Preattack. Casualties may have been taking pyridostigmine bromide, the drug currently contained in the nerve agent pretreatment sets (which are discussed later

in this chapter) if a nerve agent attack was

thought to be imminent. The state of MOPP

at the time of attack is important.

2. Self-aid. Casualties may have administered autoinjectable atropine, oximes, and

benzodiazepine before or after a nerve

agent attack. The possibility exists that the

injection may have been given without

subsequent chemical agent attack. Atropine intoxication is a theoretical possibility at this stage, causing the casualty to be

confused and compounding his heat stress,

although the amount of atropine in three

MARK I autoinjectors is unlikely to cause

significant confusion in the average 70-kg

soldier.

3. Buddy-aid. The chemically injured casualty may receive further autoject medication from a comrade, but U.S. military doctrine has no provision or method for a

buddy to provide airway management or

IPPV in a masked casualty.

4. Initial medical care (battalion aid station),

including initial triage decontamination

and ventilatory assistance.

5. Hospital level, including decontamination

and monitoring with continued integrated

medical support. A full ATLS primary

survey should be possible at this stage to

establish airway, breathing, and circulation, and to determine disability and exposure. The full ATLS primary survey can

be carried out only in a decontaminated

casualty.

During the first four phases, the casualty may be

relatively isolated from the medical attendants both

by IPE and by the use of casualty bags during

transport. Even simple maneuvers such as measuring pulse and respiration may be difficult. At the

third echelon, noninvasive monitoring should be

possible and may include pulse oximetry and

capnography. Simple observations of color and

mode of respiration, together with auscultation of

the lungs, will provide much valuable information

at this time. The anesthesia provider may be actively involved with T1 (Priority I and Priority IA)

casualties at the third echelon in securing the airway and assessing neuromuscular deficit. The use

of an endotracheal tube with early IPPV and positive end-expiratory pressure (PEEP) may be highly

desirable, and a laryngeal mask or esophageal occlusion device may be helpful.16 (Techniques for

securing the airway are discussed in Chapter 3,

Airway Management.) It is important with toxic

casualties to remember the omnipresent risk of vomiting and aspiration. Pharyngeal and bronchial

secretions are a major feature of intoxication by

several agents, particularly nerve agents, and although efficient suction for clearance is vital, the

presence of excessive secretions indicates the need

for more atropine. In fact, one of the end points for

atropine administration is minimal secretions.

Preoperative Assessment and Examination

The military anesthesia provider preoperatively

assessing any casualty must bear in mind the overall classification of casualties stated above. In particular, the possibility of contamination of a patient

who has not yet sustained toxic injury must be

considered. In a casualty with combined injuries,

the anesthesia provider must remember that the

casualty may have received pyridostigmine pretreatment, antimuscarinics such as atropine and

oximes after agent exposure, and opiates after

wounding. All of these will interact with the conduct of general anesthesia.

Toxic agents may radically alter the normal pattern of anesthesia. It is therefore vital that any

preoperative assessment should attempt to gain as

much information as possible about the circumstances and timing of toxic wounding, together

with any information that might be available about

the nature of the agents used. Examination should

concentrate on the key respiratory and nervous
Anesthesia for Casualties of Chemical Warfare Agents

845

system sites that will interfere with subsequent

general anesthesia. The possibility of latency of

onset of signs and symptoms is particularly important, as these may lead to onset of pulmonary edema

or other respiratory pathology during the anesthetic course.

The usual preoperative investigations will be

required, but these may usefully be supplemented

by some assessment of the level of acetylcholinesterase, which is depressed by nerve and mustard

agents. In the field hospital, direct estimation of

acetylcholinesterase will be difficult, but whether

abnormal serum butyrylcholine esterase (also called

plasma cholinesterase) is present can be determined

using the dibucaine test, which is familiar to anesthesiologists investigating prolonged, pathological

action of succinylcholine in a patient.17 Butyrylcholine esterase will be depressed by nerve agents to an

extent similar to acetylcholinesterase when exposure has been severe and the levels of both enzymes

are close to zero. Wherever possible, X-ray examinations of the chest should be performed—particularly after exposure to lung-damaging agents, which

carry a high risk of causing pulmonary edema.

Radiographic evidence of alveolar membrane damage may lag behind the development of pulmonary

edema but may be apparent on auscultation of the

chest.

Only limited time may be available for preoperative examination, but care should be taken to determine the casualty’s color and the rate and depth of

respiration. Diminished air entry to the lungs may

indicate the presence of secretions, which are a

major problem with nerve agents and indicate the

need for further administration of atropine.

Bronchospasm and bronchiolitis may be signs of

inhaled vesicant agent vapor as well as conventional lung-damaging agents, particularly at high

ambient temperatures. Unfortunately, the findings

of bronchospasm and bronchiolitis within 3 to 4

hours of mustard exposure indicate severe lung

damage, and the casualty should be classified in the

expectant category.

Cardiovascular assessment should follow the

ATLS procedure, but it is important to note that the

normal relationship between pulse and blood pressure in a casualty with traumatic injuries combined

with nerve agent poisoning may be totally unreliable, due primarily to administered atropine. In

casualties with nerve agent injuries who have been

inadequately treated, the normal relationship between pulse and blood pressure may also be absent

owing to the widespread action of the organophosphate at vagal and sympathetic ganglionic sites

alike. The alimentary system is unstable following

nerve agent poisoning, and the risk of vomiting is

high. Simple examination of the extremities will

reveal possible fasciculations and weakness following nerve agent exposure. If train-of-four testing is

possible at this stage, a characteristic depolarization block with no fade is most likely to be found.18

Anesthetic Induction, Maintenance, and

Recovery

Toxic injury may have serious effects on induction of emergency general anesthesia. Shock and

toxic airway injury can both produce ventilation–

perfusion inequality, giving rise to less-effective

preoxygenation. Therefore, as far as possible, the

toxic injury should be stabilized before the start of

surgical anesthesia. The responses to the inducing

agent will require careful titration; normal doses of

intravenous induction agents may not apply. With

many toxic injuries, both the risk of vomiting and

the need for controlled induction with cricoid compression are increased. If assistance is not available,

induction should be performed in the lateral position. The action of succinylcholine will be considerably prolonged if used after nerve agent exposure.

This effect will also be noted after pyridostigmine

pretreatment, owing to the anti–butyrylcholine esterase action of the carbamate anticholinesterase.19

The respiratory uptake of anesthetic vapors and

alveolar ventilation will be affected by degrees of

shunt and pulmonary edema during balanced anesthesia. Careful titration of the balance is required.

The characteristics of nondepolarizing muscle

relaxants may be particularly affected in patients

poisoned with nerve agents. Since organophosphates cause an increase of acetylcholine at the

cholinergic junctions, including the neuromuscular

junction, the normal pharmacological actions of

nondepolarizing blocking agents will be antagonized. For a severely poisoned casualty, the degree

of acetylcholinesterase inhibition will be greater

than 70%.20 There is little or no clinical experience

regarding the actions of muscle relaxants under

these conditions, but the buildup of acetylcholine at

the postjunctional folds will antagonize the action

of nondepolarizing blocking agents, leading to

higher-than-expected doses. A casualty who has

suffered severe nerve agent poisoning requiring

IPPV may have a sufficient depolarization block

from the acetylcholine increase to permit surgery,

in which case the use of nondepolarizing blocking

agents may be unnecessary. Clinical experience in

this area is very scarce. There is, however, a theo-
Anesthesia and Perioperative Care of the Combat Casualty

846

retical advantage in using nondepolarizing agents

in this situation, since the occupancy of the receptor

sites by the drug may protect the endplate from

long-term postoperative damage.

In field surgery, where the operating load may be

heavy, predictability of recovery is very important

and is the principal advantage of using balanced

anesthesia in this situation. The many possible

interactions of toxic agents with the techniques of

balanced anesthesia, in which multiple drugs are

administered, are likely to disturb this predictability and lead to postoperative complications. The

normal physiological indicators of balanced anesthesia, such as pulse rate and blood pressure, may

be compromised by the effects of toxic agents. The

reversal of nondepolarizing blocking agents may be

particularly affected, and recurrent paralysis may

occur following nerve agent poisoning. Generally,

the likelihood of continuing postoperative intensive care will be greater when conventional and

toxic injuries are combined. Given the potential

problems for balanced general anesthesia arising

from the effects of toxic agents, there may be considerable advantages in using regional blocks for general surgery in this situation. Spinal and epidural

anesthesia may be highly unpredictable from a cardiovascular point of view, where the autonomic

nervous system is affected by nerve agents.

TOXIC AGENT COMPLICATIONS OF MILITARY ANESTHESIA

adult respiratory distress syndrome is possible, and

early recognition of the syndrome is important. The

problem of doing so is compounded by the fact that

such cases will often be managed in clinically unsophisticated facilities, where blood gas analysis and

other routine intensive care investigations may not

always be available.

For postoperative casualties with toxic injuries,

some form of simple intensive care facility is necessary for the respiratory care of the more severely

affected. The equipment required may be simple

but should be capable of ventilating casualties who

have significant adverse changes in pulmonary compliance. Evacuation of ventilator-dependent patients may be desirable in certain circumstances.

Neurological Complications

The therapy of nerve agent poisoning emphasizes the early use of antimuscarinic drugs and

oximes to regenerate acetylcholinesterase, in conjunction with pyridostigmine pretreatment.1,23 This

regime should be effective in most cases, but severely poisoned casualties will require ventilatory

support. If nerve agent intoxication was sufficient

to remove all remaining acetylcholinesterase after

pyridostigmine pretreatment (about 60% of the original store), a period of time will be required for the

carbamylated enzyme to be released at the neuromuscular junction. Total ventilatory support may

be required during this period. If pretreatment has

been effective, this should last only a matter of

hours. The nature of the neuromuscular block during this period will be a classical depolarization

with a nondecremental response to train-of-four

stimuli at 2 Hz. However, military anesthesia proThe postoperative complications may be significant in patients whose field surgery is complicated

by chemical injury. The most important complications from toxic injury of concern to the anesthesia provider are to the respiratory and nervous

systems.

Respiratory Complications

Respiratory complications take the form of damage to the airways and alveoli. Vesicant agent

exposure causes slow-healing ulceration of the upper respiratory tract and large airways. If sloughing of the pseudodiphtheritic membrane occurs,

there will be blockage of bronchi with subsequent

collapse.21 Bronchopneumonia is a common sequel

to these events and was a primary cause of death

from mustard poisoning during World War I.

Bronchoscopic intervention may be required in such

cases. Cases of mustard inhalation reported from

the Iran–Iraq War have shown that mustard will

affect the terminal airways, in some cases causing a

chemical bronchiolitis. This can give rise to severe

bronchospasm, which may present difficulties in

weaning from a ventilator (—DJB, personal observation, 1988). In some casualties, intractable

bronchostenosis developed after several years.22

Pulmonary edema occurs with vesicants only

after extremely high exposure or as a terminal event

days after exposure. After an extremely high exposure, patchy pulmonary edema may occur within

hours of exposure and is also a preterminal event. It

is unlikely that a surgical procedure would be undertaken under either of these circumstances. The

value of early IPPV with PEEP and high-dose steroid therapy is controversial. Development of the
Anesthesia for Casualties of Chemical Warfare Agents

847

viders must recognize that long-term ventilatory

support, indicative of long-term paralysis, is uncommon. With no pretreatment, individual case

reports indicate that paralysis and the need for

ventilatory support do not persist for more than 2 to

3 hours.24

The experience with nerve agents is in contrast to

what is seen with organophosphate pesticide poisoning,25 in which the initial block, during the cholinergic phase, may disappear within a few hours.

After about 18 hours, however, the block recurs,

this time having the characteristics of nondepolarizing block with a decremental response to trainof-four stimulation monitoring. This recurrent paralysis has been termed the intermediate syndrome,

and is the phase of neurotoxicity when nerve conduction itself is affected, giving rise to sensory and

motor dysfunction. The final phase may be mediated by direct neurotoxic actions of organophosphate pesticides rather than through acetylcholinesterase. The neuromuscular block of the intermediate

syndrome may be persistent, lasting in some instances as long as several weeks. It may be analogous to the much-debated concept of dual block

seen after multiple doses of succinylcholine.26 If the

intermediate syndrome occurs, improvement may

be seen in neuromuscular transmission following

administration of neostigmine.25 There is supporting evidence, from studies using single-fiber electromyography following low-dose sarin exposure

in volunteers, that subclinical, nondepolarizing

neuromuscular failure occurs even at modest levels

of acetylcholinesterase inhibition 3 days after exposure.27 It is important for military anesthesia providers to know that the intermediate syndrome has

not been seen in thousands of experimental animals

and in the limited number of humans inadvertently

exposed to nerve agents. Furthermore, recently

published experiences with organophosphate pesticide poisoning suggest that the delayed respiratory insufficiency is due to pulmonary complications such as secondary pneumonia rather than to

respiratory muscle insufficiency per se.28

The use of diazepam may prevent neurological

complications from seizure activity as well as decrease spasm from excessive acetylcholinesterase

stimulation.

Nondepolarizing Neuromuscular Blocking

Agents in Organophosphate Poisoning

Although the intermediate syndrome has not

been described in experimental animals or in humans after nerve agent exposure, it should be kept

in mind that the experience with humans is quite

limited. It is possible that the intermediate syndrome may become apparent given large numbers

of nerve gas casualties. If so, theoretical and experimental considerations suggest the following therapeutic approach. Nerve agents cause a prolonged

depolarization at the neuromuscular junction, which

may lead to secondary changes in the acetylcholine

receptors. One therapeutic possibility to avoid the

intermediate syndrome is to block the receptor sites

with long-acting, nondepolarizing blocking agents

such as curare or pancuronium. Competitive denial

of access of acetylcholine to the receptors may alter

the processes leading to the development of the

intermediate syndrome. With the present state of

knowledge regarding the long-term block following exposure to nerve agents, this approach can

only be regarded as conjecture. However, the anesthesia provider will feel confident in the use of the

nondepolarizing drugs in long-term ventilation in

the intensive care unit and will have available a

therapeutic tool in an area that has little else to offer

at present. Further research on the long-term block

is needed before any definitive advice can be given.

PYRIDOSTIGMINE PRETREATMENT AND GENERAL ANESTHESIA

Pretreatment with carbamate anticholinesterases

is now an established technique whenever there is a

risk of exposure to nerve agents. The drug used at

the present time is pyridostigmine bromide, 30 mg

given every 8 hours. The first large-scale use of

pyridostigmine under field conditions occurred

during the Persian Gulf War,15 based on efficiency

studies in animals.29 The complete rationale and use

of pyridostigmine pretreatment is described in U.S.

Army Field Manual 8-285, Treatment of Chemical

Agent Casualties and Conventional Military Chemical

Injuries.

1 This use of pyridostigmine may have

important consequences of which military anesthesia providers must be aware.

Pharmacology

Pyridostigmine bromide is a dimethyl carbamate

compound containing a quaternary amine site. It

does not, therefore, readily penetrate the blood–

brain barrier. In usual doses, its actions are peripheral, and only high doses might cross the barrier
Anesthesia and Perioperative Care of the Combat Casualty

848

and have central nervous system actions. Like

other carbamates such as neostigmine and physostigmine, pyridostigmine is an anticholinesterase

compound. Therefore, it has the same action as the

organophosphates, but unlike the latter it forms a

reversible complex with acetylcholinesterase.

Pyridostigmine has no significant plasma-protein

binding, indicating that there should be no drug

interactions involving competition for binding sites.

Seventy percent to 90% of the absorbed dose is

excreted unchanged in the urine. At the normal

pretreatment dose of 30 mg every 8 hours, the

anticholinesterase level returns to within 10% of

normal 12 hours after the last dose.30

Mild and reversible symptoms associated with

taking the prescribed prophylactic dose have been

well described (Table 30-3).15 Another study8 found

that more than 10% of 200 uninjured personnel who

were taking pyridostigmine pretreatment reported

significant side effects including abdominal cramps,

increased volume and frequency of stools, flatulence, increased salivation, sweating, headache, and

various eye signs including difficulty in focusing

and dimness of vision. Isolated reports of moreserious problems such as hypertension were also

reported.8 In addition, two women with body

weights of 45 to 50 kg experienced increased salivation, severe abdominal cramps, nausea, diaphoresis, and muscular twitching—all signs of pyridostigmine overdose. Symptoms were found to usually

begin within hours of taking the first tablet and

were often decreased if the pyridostigmine was

taken with a meal.

Protective Action Against Organophosphates

At the pretreatment dosage schedule, pyridostigmine combines with part of the acetylcholinesterase

enzyme store to produce a carbamylated complex,

which is resistant to subsequent attack by an organophosphate. If a person taking this regime is

exposed to nerve agent in a potentially lethal dose,

the remaining free acetylcholinesterase will bind

irreversibly to the organophosphate, causing a

buildup of acetylcholine. However, the carbamylated portion of the enzyme spontaneously breaks

down, regenerating free enzyme and effectively

providing an autotransfusion of enzyme at the

postjunctional membrane. This process does not

require the presence of oxime; oxime has no effect

on the carbamate–enzyme bond. This new free

enzyme is not attacked by nerve agent, because the

latter is rapidly broken down in plasma after exposure. There is a considerable safety margin in normal acetylcholinesterase levels present at the neuromuscular junction, and the amount of enzyme

released from the pyridostigmine complex is sufficient to restore neuromuscular transmission. The

restoration of enzyme in conjunction with the usual

resuscitative measures offers a therapeutic solution

to the potentially lethal poisoning by nerve agent.

Interactions Between Pyridostigmine and Drugs

Used in General Anesthesia

U.S. Army Lieutenant Colonel Jill R. Keeler has

reviewed the possible interactions of pyridostigmine

pretreatment on the subsequent management of

general anesthesia, based on the known pharmacological activity at cholinergic synapses, and her

papers should be consulted for a thorough review

of the subject.19,31 There is very little clinical information on which to draw to confirm these possibilities. The degree of interaction will be related to the

amount of acetylcholinesterase inhibition. At the

usual pyridostigmine pretreatment dosage, this is

usually 40%. Military anesthesia providers should

allow for changes in the normal pharmacokinetic

profile produced by delayed gastric emptying

caused by factors such as traumatic wounding. In

this situation, the degree of enzyme inhibition may

be less predictable. The possible effects may best be

considered in terms of the anesthetic process.

TABLE 30-3

EFFECTS OF PYRIDOSTIGMINE

PRETREATMENT*

Range of Incidence

Effect (%)

Gastrointestinal symptoms > 50

Urinary urgency and frequency 5–30

Headaches, rhinorrhea, diaphoresis,

tingling of extremities < 5

Need for medical visit 1

Discontinuation on medical advice < 0.1

*Based on reports from medical personnel providing care to

41,650 soldiers (6.5% women) who took pyridostigmine bromide orally, 30 mg every 8 h for 1–7 d. Drug administration

resulted in 483 clinic visits, and use of the drug was discontinued in 28 soldiers.

Reprinted from Keeler JR, Hurst CG, Dunn MA. Pyridostigmine

used as a nerve agent preteatment under wartime conditions.

JAMA. 1991;266(5):694.
Anesthesia for Casualties of Chemical Warfare Agents

849

Premedication

In field anesthesia, formal premedication may be

comparatively rare. Opioids will often have been

administered for pain following wounding.

Antimuscarinic drugs are usually given as part of

the induction. The cholinergic agonist activity of

pyridostigmine would be expected to antagonize

the action of such agents as atropine and hyoscine.

In most Priority I, IA, and II casualties with either

traumatic or toxic wounding or both, the notion of

conventional premedication is largely academic;

however, the anesthesia provider should be aware

of the potential problem and be prepared to administer larger-than-usual doses of atropine.

Induction Agents

Sodium thiopental can provoke asthma in susceptible subjects. Pyridostigmine, through its muscarinic activity, may aggravate this situation but

clinical evidence is not available. Thiopental is not

considered by some to be an induction agent of

choice in a hypotensive battle casualty, particularly

when time for preoperative stabilization may be

limited. The drug causes a fall in cardiac index,

stroke volume, and blood pressure. In theory,

pyridostigmine may cause a fall in cardiac output

due to its vagal action and subsequent bradycardia.

There is, therefore, a risk of synergism between the

two drugs, and thiopental may best be avoided.

Arylcyclohexamines such as ketamine have an established place in field surgery because they provide good cardiovascular support. Heart rate, contractility, cardiac output, and blood pressure are all

maintained owing to sympathetic activity. These

will tend to antagonize the muscarinic actions of

pyridostigmine. Both pyridostigmine and ketamine

increase oral secretions. This may increase the risk

of laryngospasm following sensitization of the larynx by ketamine.

Neuromuscular Blocking Agents

Balanced anesthesia involving the use of relaxants with endotracheal intubation and IPPV is highly

desirable in field surgery because (a) delayed gastric emptying associated with stress during combat

means that patients presenting for operation must

be assumed to have full stomachs, and (b) in a

situation where casualties may be numerous and

the operative flow heavy, predictable anesthesia

and recovery are essential. To achieve success when

relaxants are in use, the effects of pretreatment on

their characteristics should be considered. As an

anticholinesterase, pyridostigmine can affect neuromuscular blockade in three ways: by directly affecting depolarization block, by antagonizing nondepolarizing block, and by effects on repeated

stimuli used to assess the degree of nondepolarization block.

Action of Pretreatment on Depolarization Block

Depolarization-blocking drugs such as succinylcholine and decamethonium are structurally related to acetylcholine and work effectively as agonists. In normal neuromuscular transmission,

acetylcholine reacts with receptors at the postjunctional folds to produce a depolarization, which induces a muscle action potential in the fiber controlled by the junction. The depolarization is usually

short-lived owing to the rapid hydrolysis catalyzed by acetylcholinesterase. Unlike acetylcholine,

depolarizing blocking agents are not affected by

acetylcholinesterase, and the depolarization they

produce lasts for a longer period than acetylcholine lasts. It might be expected that pyridostigmine

and the standard depolarization blocking agents

would be synergistic in their actions, but the degree

of significance of the interaction at the targeted

pyridostigmine-induced acetylcholinesterase inhibition level of 30% to 40% has yet to be determined.

Apart from considerations of synergism, a more

important effect of pyridostigmine is on butyrylcholine esterase. This enzyme is found at many

sites in the body, including the plasma, where it is

responsible for the normal hydrolysis of succinylcholine. The genetic homozygotic and heterozygotic

possibilities controlling the enzyme give rise to the

well-recognized syndrome of succinylcholine apnea.

Pyridostigmine may cause an unpredictable extension in the duration of action of succinylcholine.

Action of Pyridostigmine on Nondepolarizing

Agents

Carbamate anticholinesterases such as neostigmine and pyridostigmine are used routinely to reverse the action of nondepolarizing blocking drugs.

They do this by inhibiting the catalytic breakdown

of acetylcholine at the postjunctional folds. The

concept of giving the reversal drug before the relaxant, however, is far less familiar and may be expected to produce changes in the rate of onset and

the minimum level of paralysis produced. Experimental studies32 have indicated that pyridostigmine does not significantly alter the characteristics
Anesthesia and Perioperative Care of the Combat Casualty

850

of neuromuscular block in adductor pollicis in the

isolated human forearm, and therefore the clinical

significance may be minimal. Since more central

muscles, such as the diaphragm, may have a higher

safety margin of neuromuscular transmission, the

results on adductor pollicis are a good indicator

that pretreatment is unlikely to produce significant

clinical effects on the subsequent use of nondepolarizing blocking agents. In practical terms, careful

titration of the dose of blocking agents will be necessary to ensure ideal clinical conditions. Electrophysiological studies following pyridostigmine pretreatment have shown little change in jitter,

indicating no significant neuromuscular effect of

the pretreatment schedule itself.27

Effect of Pretreatment on Neuromuscular

Monitoring

Train-of-four stimulation monitoring is widely

used to assess the degree of recovery of neuromuscular block. Pyridostigmine has a prejunctional, as

well as a postjunctional, action. The prejunctional

neuromuscular site is thought to be the determinant

of fade through a positive feedback mechanism.33

Therefore, alterations of the conventional fade–block

relationship18 may be possible, and predictions of

neuromuscular block may be inaccurate. Experimental evidence in the isolated forearm indicates

that the hysteresis relationship between T1 and T4

(of the train-of-four) during onset and recovery of

relaxation (differential fade) is unaltered by

pyridostigmine.31

Inhalational Anesthetics

The anticholinesterase activity of pyridostigmine

may give rise to bronchospasm in patients with

asthmatic tendency. Inhalational anesthetics such

as isoflurane, enflurane, and halothane have a

bronchodilator effect, which might antagonize any

sensitization of the bronchi by pyridostigmine. In

addition, the inhalational agents potentiate the actions of nondepolarizing neuromuscular blocking

drugs. This may be an advantage in pyridostigminepretreated patients in removing the need for increased dosage of relaxant drugs.

Military Clinical Experience

During the 1991 Persian Gulf War, the number of

casualties sustained by the alliance forces was relatively low. Some of these were taking pyridostigmine in anticipation of nerve agent attack. In three

casualties with gunshot wounds who were taking

pyridostigmine pretreatment and who also required

surgery, a technique of total intravenous anesthesia

using ketamine, midazolam, and vecuronium was

used. Atropine premedication was required because of significant salivation. There was no obvious extension of the action of suxamethonium bromide used for intubation, but there were indications

that a larger-than-usual dose of vecuronium was

required. It is not clear whether this was due to the

total intravenous anesthesia technique or to the

pyridostigmine pretreatment. The casualties were

all operated on at least 7 hours after taking the last

dose of pyridostigmine, and by this stage only about

10% of the acetylcholinesterase could be expected

to be complexed. Although these findings are anecdotal, they are a useful indicator for general anesthesia following pyridostigmine pretreatment. The

observations on the side effects, in particular, are at

variance with previous studies, although it should

be noted that the battlefield observations were uncontrolled.

SUMMARY

In the past, military anesthetic policy and experience have largely been involved with conventional

physical trauma rather than chemical injury. The

continuing risk of casualties from chemical warfare

agents enforces a wider view, encompassing casualties who may be suffering from physical, toxic, or

environmental trauma, or from any combination.

Chemical agent injury may affect all body systems,

and military anesthesia providers may be involved

in its management either directly or as part of the

perioperative management of coincident physical

trauma. Chemical casualties should be expected at

any time during conflict and not just in unique

circumstances, and chemical weapons should now

be considered as tactical weapons rather than necessarily as weapons of mass destruction. Preparations for chemical agent casualties should, therefore, be made in all military actions, particularly

those involving rapid-response forces in unusual

areas.

The concept of chemical weapons has now been

extended to cover agents previously described as

toxins or biological agents. A spectrum of toxic

agents exists, in which agents that differ considerably in their physical nature may have common

pathophysiological pathways of clinical damage.
Anesthesia for Casualties of Chemical Warfare Agents

851

The chemical–biological warfare spectrum reminds

military anesthesia providers of the need to respond to the dysfunction of systems rather than

solely to the specific management of individual

toxic agents. All agents in the spectrum possess

three main characteristics: toxicity, latency of action, and transmissibility. The serious consequence

of transmissibility is that toxic agents, unlike other

weapons, pose a continuing danger to medical attendants down the evacuation line.

Military anesthesia providers must be totally familiar with current teaching about protection, detection, and decontamination of toxic agents. The

use of CAM and ICAD will facilitate all practices.

IPE-MOPP gear may be required for anesthesia

providers working at early stages of casualty management. These protective ensembles will enforce

isolation from the casualty and make difficult the

contact necessary for simple monitoring and airway management. When the casualty’s life is threatened, it may be necessary to remove his respirator

to gain access to the airway, since the dangers from

the existing respiratory failure may outweigh the

risks from further inhalation of the agent. Collective protection offers greater freedom for casualty

assessment, resuscitation, and anesthesia, but conditions may be cramped.

Much as the knowledge of the type of trauma

sustained may be a useful predictor of the nature of

physical injury, so knowledge of the toxic agent

may also predict the extent of toxic injury. This is

particularly true in the case of long-latency agents,

where the symptoms and signs may not yet have

fully developed. In some instances, specific knowledge of the agent used may not be available, and

treatment should be based on the casualty’s presenting signs and symptoms. Toxic agents may

affect the skin, viscera, blood, mitochondria, central

and peripheral nervous systems, and the respiratory system. In the last category, agents may affect

the respiratory center, respiratory muscles, nasopharynx, larynx, large and small airways, and the

alveoli. Careful clinical assessment of all systems is vital. Signs present in one system may

provide valuable clues about developing pathology in others.

The responsibilities of the anesthesia provider in

the management of toxic injury start with planning

in the preattack phase. Specific responsibilities

include being knowledgeable about the hospital’s

plans for casualty reception, including decontamination and resuscitation of chemical casualties.

Military anesthesia providers will be intimately

involved in preoperative assessment of prophylactic measures, toxic agent effects, and therapeutic

measures on the subsequent course of anesthesia.

They may be asked to advise surgeons on toxic

morbidity factors; the perioperative management

of casualties with combined conventional and chemical injuries; and the management of toxic, anesthetic, and surgical postoperative complications,

including intensive care.

A system of triage must be created for casualties

who have been exposed to toxic agents, and conventional triage systems should be modified to take

account of toxic factors. Careful preoperative assessment is required, since toxic factors may radically alter the normal patterns of anesthesia. The

respiratory and neuromuscular systems are particularly important. Induction and maintenance of,

and recovery from, general anesthesia may all be

affected by toxic injury and its therapy. A casualty’s

responses to neuromuscular blocking drugs may

particularly be altered after nerve agent exposure.

The action of succinylcholine may be prolonged

and the nondepolarizers antagonized. Nerve agent

paralysis itself may permit surgical intervention

but is likely to be unreliable. Given the problems

posed to general anesthesia, careful consideration

must be given to the use of regional anesthetic

techniques; spinal and epidural anesthesia may,

however, provoke unstable cardiovascular responses after nerve agent attack.

Postoperative complications may be significant.

Serious and frequently fatal damage to the large

and small airways can result from the inhalation of

droplets or vapor of vesicant agent. Pulmonary

edema is a consequence of several toxic agents,

including conventional lung-damaging agents (eg,

phosgene) and vesicants (eg, mustard gas). Neurological complications may follow nerve agent poisoning. Evidence from organophosphate pesticide

poisoning, but not so far with nerve agents, indicates a relapse of neuromuscular paralysis 24 hours

after exposure and following apparent recovery

with atropine and oxime treatment (the intermediate syndrome). The recurring paralysis is nondepolarizing in nature. There may also be a later

stage of peripheral neuropathy. Toxic complications will increase the likelihood of postoperative

intensive care.

Pretreatment with pyridostigmine as a prophylaxis against nerve agent poisoning has several implications for military anesthetic practice. Inhibition of butyrylcholine esterase may cause the action

of succinylcholine to be prolonged. Although experimental studies have not indicated significant

antagonism of the action of nondepolarizing relax-
Anesthesia and Perioperative Care of the Combat Casualty

852

ants, clinical experience in this area is scarce. Reports of casualties who had taken pyridostigmine,

and who subsequently received total intravenous

anesthesia for surgery following traumatic, not toxic

agent, injuries, indicate that the amount of

vecuronium required may possibly be increased.

At present, it may be said that pyridostigmine pretreatment adds to the uncertainty of clinical anesthesia for incidental operative intervention.

There has been very little recent experience of

anesthesia after toxic injury in warfare, and the

subject still remains one of speculation. Good planning and familiarity with standard procedures will

reduce the undoubted difficulties likely to be encountered in the anesthetic interface with casualties

of toxic weapons.

REFERENCES

1. US Departments of the Army, the Navy, and the Air Force. Treatment of Chemical Agent Casualties and

Conventional Military Chemical Injuries. Washington, DC: HQ DA, DN, DAF; 28 February 1990. Army Field

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Acknowledgment

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Medical Management of Chemical Casualties Course, U.S. Army Medical Research Institute

of Chemical Defense, Aberdeen Proving Ground, Maryland, for his expert scientific and doctrinal

review of this chapter in its developmental stages.
Anesthesia for Casualties of Chemical Warfare Agents

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15. Keeler JR, Hurst CG, Dunn MA. Pyridostigmine used as a nerve agent pretreatment under wartime conditions.

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17. Kalow W, Ganest K. A method for the detection of atypical forms of human serum cholinesterase: Determination

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18. Ali HH, Savarese JJ. Monitoring of neuromuscular function. Anesthesiology. 1976;45:216–249.

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1987;227–234. AD B121516.

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32. Turner GA, Williams JD, Baker DJ. Effects of pretreatment with pyridostigmine on subsequent activity of

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A Brief History of Military Anesthesia

855

MARY ELLEN CONDON-RALL, PH.D.*

Chapter 31

A BRIEF HISTORY OF MILITARY

ANESTHESIA

INTRODUCTION

EARLY ANALGESICS

THE EVOLUTION OF ANESTHESIA

The Discovery

The Mexican War

The American Civil War

Late–19th-Century Advancements

The Spanish–American War

World War I

Between the World Wars

World War II

The Korean War

The Vietnam War

The Post–Vietnam War Era

SUMMARY

*Military Studies Branch, Center of Military History, Department of the U.S. Army, Washington, D. C. 20005-3402
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For 150 years, the medical departments of the

U.S. military have provided state-of-the-art anesthesia within the limitations imposed by the battlefield. From the Mexican War (1846–1848), when the

first anesthetic was administered during military

surgery, to the Persian Gulf War (1990–1991),

military medicine has adapted civilian advances

in anesthesiology for use in wartime. Those advances included new drugs, new techniques, new

machines, and an expanded role for the anesthesia

provider. In turn, the civilian practice of anesthesiology has benefited from lessons learned on the

battlefield.

For most of this period, civilian anesthetists counseled the military about what to bring and what to

INTRODUCTION

leave at home during deployment. Complex and

cumbersome machines, logistical priorities, and the

need for simplicity at the front complicated the

provision of modern anesthesia in war. By the

Vietnam War, however, the military had its own

anesthesia specialists and was no longer dependent

on civilian medicine for advice. In the 1960s, the

field of military anesthesia produced intensive care

specialists and a decade later, practitioners of critical care. Critical care medicine led to a natural

alliance of military and civilian anesthesiology in

the treatment of trauma.

This chapter is intended to be a brief survey, not

a comprehensive study, of the events surrounding

the history of military anesthesia.

EARLY ANALGESICS

Man has tried to conquer pain since the beginning of recorded history. Primitive peoples sought

pain relievers in herbs, roots, seeds, flowers, opium,

mandrake, hemlock, the mulberry tree, and even

the garden lettuce, among other remedies. A sea

sponge saturated with the juices of soporific plants

became the major analgesic of the Middle Ages, although drugged wine, “not enough drug to be poisonous,” but sufficient to put one to sleep, was considered the safest anesthetic. By the middle of the 17th

century, whiskey, gin, and rum had replaced most

drugs, considered unsafe since there was no way to

standardize dosage, although occasionally physicians used opium. The search for a successful anesthetic continued, but, “in practice, the reduction of

pain depended upon the speed of the surgeon.”1(p44)

The fear of pain kept patients from committing

themselves to the surgeon’s knife. Many preferred

to risk death than to undergo the terrible agony of

an operation while fully conscious. Once strapped

to the table, some screamed and struggled, begging

the surgeon to be quick; some “fell into a trance-like

state,” which made the operation easier but did not

bode well for their recovery; some cursed or prayed;

some endured bravely and quietly; others wept and

fainted (Figure 31-1). All suffered “severe nervous

Fig. 31-1. Surgery and anesthesia before ether (ca 1800). Photograph:

Courtesy of William Clayton Petty,

MD, Captain, Medical Corps, US

Navy, Bethesda, Md.
A Brief History of Military Anesthesia

857

shock” and afterward a “long period of depression,”2(pp505–506) which interfered with healing and

delayed convalescence. Only recently have scientists discovered that severe pain actually produces

chemical imbalances in the brain that can cause

depression and death. The 19th-century British

surgeon Sir Benjamin Richardson wrote:

I have heard many express that if they had known

beforehand what the suffering was, and the effects

subsequently endured, they would rather have

faced death than such a fearful struggle for continued existence.2(pp505–506)

The presence of pain also interfered with the

development of surgery as a science. Because of the

patient’s fear of pain, and the surgeon’s unwillingness to operate except in traumatic amputations or

as a last resort, when all else had failed, operations

were few in number. They also were few in kind,

because of the necessity of devising operations that

could be done quickly. In the 18th century, these

were chiefly confined to the surface of the body,

including excision of tumors, amputation of limbs,

various plastic operations, cataract removal,

lithotomy, and herniotomy. With pain such a barrier to good surgery and the saving of life, it is not

surprising that men through the centuries have

sought ways to alleviate it.2

THE EVOLUTION OF ANESTHESIA

The search for a successful anesthetic received

great impetus with the discovery of gases and their

effects on respiration. In 1772, the Englishman

Joseph Priestley discovered nitrous oxide gas (Figure 31-2). Twenty-eight years later, Humphry Davy

determined that nitrous oxide destroyed physical

pain and suggested the anesthetic possibilities of

the agent (Figure 31-3). In 1818, Michael Faraday

noted the soporific effects of sulfuric ether after

breathing the gas himself and anesthetizing a cat.

His achievement received little attention. In 1824,

Henry Hill Hickman, another Englishman, successfully anesthetized animals with carbon dioxide,

introducing the principle of anesthesia by inhalation. His published results became the first separate publication on anesthesia. In their day, Davy’s,

Faraday’s, and Hickman’s discoveries received

slight notice.1,3

Hypnosis as a method of pain relief received

impetus from the work of Franz Anton Mesmer

(1734–1815) of Vienna, which advocated “animal

magnetism” as a cure for body ailments. Although

contemporary physicians and scientists thought of

him as a quack, Mesmer had followers in Britain,

the United States, and India who claimed to have

performed operations under mesmerism. Apostles

of somnambulism, a development of mesmerism,

became convinced of its ability to relieve pain during surgical procedures. Also, James Braid of

Manchester believed that hypnotism could either

moderate the pain or produce a state whereby the

patient was unaware of the pain. Although other

practitioners of surgery failed to produce painless

operations with this method, their attempts helped

to establish a mind-set for the possibility and acceptance of surgery without pain.1,3

Pain continued to dominate surgery and interfere with its advancement as a science. Then the

discovery of ether anesthetic changed everything.

The Discovery

The search for painless surgery has many precursors, but four names will always be linked with its

discovery, each vying for the honor of being the

discoverer of anesthesia and each with his own

partisans. Crawford W. Long (Figure 31-4), a Georgia physician, in 1842 excised two tumors from a

patient under ether but delayed publication of the

event and lost the worldwide recognition he might

have received.

Horace Wells, a dentist from Hartford, Connecticut, used nitrous oxide (laughing gas) in his practice in 1844 but was unable to stage a successful

public demonstration of the gas in surgery in Boston, Massachusetts. Although ridiculed after his

failure, he continued to use nitrous oxide on his

own patients. William T. G. Morton, a Boston dentist, used ether to extract a patient’s abscessed tooth

(Figure 31-5). Morton had witnessed Wells’s experiments with nitrous oxide and had followed the

suggestion of Charles Thomas Jackson, a chemist,

to use pure ether instead of laughing gas.

On 16 October 1846, a little more than a fortnight

after the painless tooth extraction, Morton successfully demonstrated ether anesthesia in a surgical

operation at Massachusetts General Hospital. This

staging of the first successful demonstration of ether

anesthesia resulted in a gradual acceptance and graded

application of this method for painless surgery. Jackson claimed the triumph for himself because of his

suggestion to use ether instead of nitrous oxide.
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Fig. 31-3. (a) Sir Humphry Davy (1778–1829) was the first to describe the analgesic properties of nitrous oxide. This

steel engraving was made from a portrait by Thomas Phillips, which was painted in 1826 when Davy was President

of the Royal Society. (b) In 1800, at the age of 22, Davy published his first major contribution in what became a

magnificently productive career. Photograph (a): Reprinted with permission from Nuland SB. The Origins of

Anesthesia. Birmingham, Alabama: The Classics of Medicine Library, Gryphon Editions, Ltd; 1983: 190. Photograph

(b): Reprinted with permission from the American Society of Anesthesiologists, Park Ridge, Ill.

a

Fig. 31-2. Joseph Priestley (1733–1804) is the man most responsible for introducing modern chemical and physical

studies of gases. A politically controversial, nonconformist minister, he produced and described nitrous oxide in 1772.

Photograph: Reprinted with permission from Thomas KB. The Development of Anaesthetic Apparatus. Oxford, England:

Association of Anaesthetists of Great Britain and Ireland, Blackwell Scientific Publications; 1975: 106.

b
A Brief History of Military Anesthesia

859

Fig. 31-5. (a) This famous painting by artist Robert Hinckley (1853–1941), “The First Operation With Ether,” shows

William Thomas Green Morton (1819–1868) first publicly administering sulfuric ether to a surgical patient on 16

October 1846 in the Massachusetts General Hospital surgical amphitheater. (b) Morton’s ether inhaler (1846). This is

a replica of the apparatus used in the first successful public demonstration of ether anesthesia. Photograph (a):

Reprinted with permission from John Knowles, MD, and Henry R. Viets, MD, Boston, Mass. In: JAMA. 1965;194(2):cover.

Photograph (b): Reprinted with permission from the Charles King Collection of Historic Anaesthetic Apparatus

(Colour Slide Collection), Association of Anaesthetists of Great Britain and Ireland, London, England.

b

a

Fig. 31-4. Crawford Williamson Long administered ether

for a surgical procedure 4 years before the public demonstration of ether anesthesia by William T. G. Morton. This

photograph, one of the few known of Long (1815–1878),

from Jefferson, Georgia, was probably taken between

1854 and 1861. It depicts a staged demonstration of an

amputation under ether anesthesia. Long is believed to

represent the “surgeon”; his brother, the “anesthetist,”

holds an ether-impregnated cloth over the mouth and

nose of the “patient.” Photograph: Reprinted with permission from Special Collections, Briscoe Library of The University of Texas Health Science Center, San Antonio, Tex.
Anesthesia and Perioperative Care of the Combat Casualty

860

Like so many other discoveries, ether anesthesia

was the culmination of many hours of research and

discovery, and to many belong the credit. Regardless of who gets the honor, ether anesthesia remains

one of the most important discoveries in the history

of medicine and an essential element in the development of the art of surgery.1,4

Improvements in ether administration began

appearing from the time of its discovery. The original method of dropping ether on cloths and inhaling it from them gave way to ether administration

by means of an inhaler apparatus, which produced

more uniformly successful results. The first ether

inhaler, designed by William Morton and used by

him from the first, consisted of a glass globe containing an air hole, a glass tube, and a mouthpiece

with valves that permitted the patient to inhale a

mixture of ether and air into his lungs and exhale

the breathed vapor into the room.

By the spring of 1847, nasal inhalation—breathing ether through the nose—was in use. A simple

sea sponge shaped to fit the face and then saturated

with ether replaced Morton’s cumbersome glass

vessel. Meanwhile, Morton patented his invention

and tried unsuccessfully to sell it to the U.S. government for use on the Mexican front.1,5

The Mexican War

Military anesthesia received its baptism of fire

during the Mexican War (1846–1848), when a U.S.

Army contract physician directed the use of diethyl

ether to an accidentally injured teamster in General

Winfield Scott’s command. In the spring of 1847,

using an ether-dispensing apparatus that he had

brought with him to Veracruz, Edward H. Barton,

surgeon of the Third Dragoons, Cavalry Brigade,

Twiggs’ Division, successfully anesthetized the

patient before the amputation of both legs. An

eyewitness to the surgery proclaimed:

The unfortunate man was soon rendered completely

insensible to all pain, and indeed, to everything

else, and the limb was removed without the quiver

of a muscle.6(p30)

The first military use of anesthesia was a resounding success.

Despite this triumph, a number of surgeons remained skeptical of the new discovery, complaining of its dangerous side effects. U.S. Army surgeon

John B. Porter attributed severe hemorrhage during

an amputation in summer, 1847,

to the pernicious influence of the ether. [He remarked that] anesthetics poison the blood and depress the nervous system, and, in consequence,

hemorrhage is more apt to occur, and union by

adhesion is prevented.7(p18)

He considered anesthetic agents to be unnecessary

and even injurious in the treatment of gunshot

wounds and, at the end of the war, decided never to

use them again. Future anesthesiologists would

know that ether evaporates more quickly at warmer

temperatures; that soldiers in pain, shock (ie,

hypovolemia), and hemorrhage respond differently

to the anesthetic; and that a low cardiac output

increases sensitivity to the depressant action of

anesthetics.7–9

Porter also believed painless surgery to be an

unnecessary interference in the soldier’s development of healthy, masculine endurance, a view held

by military surgeons on both sides of the Atlantic.

“Heroic manly fortitude, heightened by the ‘excitement’ of battle, rendered soldiers insensitive to the

pain of ‘almost any operation,’”10(p150) declared British

military surgeon Rutherford Alcock. At this time,

most military surgeons scoffed at surgical anesthesia

as a product “of misguided effeminate sentimentalism.”10(p146) In 1847, this viewpoint, plus fear of the

unfamiliar, prejudice, and staunch opposition to

change, blinded army surgeons to the value of ether.

As a result, they used anesthesia sparingly during the

Mexican War and forfeited an opportunity to contribute significantly to the growth of the new science.1,10

In 1849, however, the almost universal acceptance of ether anesthesia prompted the U.S. Army

to order an allowance of 2 lb of sulfuric ether for

every 100 men, officially sanctioning the drug’s

use. The army added chloroform, discovered in

1847, to its list of regular drugs for the purpose of

testing its advantages in surgical operations. Although occasional sudden convulsions and deaths

were attributed to chloroform, the drug had certain

advantages over ether: small doses of chloroform

would put the patient to sleep quickly and peacefully; and the drug was neither flammable, a matter

of considerable concern during the days of operations by candlelight, nor odorous like ether. Therefore, chloroform was more pleasant to take.

The administration was made easier by Englishman John Snow’s development of a chloroform

inhaler (Figure 31-6). This device, composed entirely of metal, a conductor of heat, and placed in

contact with water to regulate temperature, enabled the anesthetist to control the strength of the
A Brief History of Military Anesthesia

861

Fig. 31-6. (a) The Englishman John Snow (1813–1858) was the first physician to specialize in anesthesia. (b) He

produced this chloroform inhaler in February 1848. Snow devoted his life to making the art of anesthesiology a science;

he also made lasting contributions to epidemiology. Photographs: Reprinted with permission from Shephard DAE.

History of anaesthesia: John Snow and research. Can J Anaesth. 1989;36(2):224, 230.

vaporized air. Chloroform became the drug of

choice for British surgeons. U.S. surgeons used

chloroform for eye surgery but preferred ether for

other operations, considering its odor the only significant drawback. Military surgeons used both

anesthetics.7,11,12

During the War in the Crimea (1853–1856), the

British army used chloroform almost exclusively,

and the French employed the agent often. George

H. B. Macleod, a British surgeon, became convinced

of chloroform’s attributes as a result of his experiences during the war. The Crimean War

has shown that chloroform, both directly and indirectly saves life; that it abates a vast amount of

suffering; that its use is as plainly indicated in

gunshot as in other wounds; that if administered

with equal care, it matters not whether the operation about to be performed be necessitated by a

gunshot wound, or by any of the accidents which

occur in civil life.13(p126)

Although sulfuric ether and chloroform became

the two most popular anesthetics before the American Civil War, civilian physicians tried other agents.

Surgeons at the Massachusetts General Hospital

preferred chloric ether, which is chloroform dissolved in alcohol in assorted ratios, to regular chloroform or ether. Other products cited in the literature of the time included morphine, cocaine,

ethylene, amylene, and a method called “the vapor

of Benzid.” Some very conservative surgeons used

none of the anesthetic agents then on the market,

relying instead on the old standbys of alcohol and

opium. One surgeon declared: “[I]f my patients

will have an anesthetic agent [I] will give them as

much good whiskey as they will drink.”7(p19) Some

surgeons believed that opium prevented inflammation by lowering irritability.7

Between the Mexican War and the American

Civil War, most surgeons practiced anesthesia conservatively and selectively, using it only some of

the time and only on people meeting certain criteria. The Massachusetts General Hospital performed one of three “potentially painful” operations

without anesthesia in 1847 and 1848.10(p190) The

patient’s age, gender, condition, and the type of

a b
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862

operation to be performed influenced the surgeon’s

decision about whether to anesthetize. Children

received anesthesia more than anyone else. Women

received anesthesia in 69% of minor operations, and

men in 50%.10(p191) Surgeons made the judgment that

men did not need anesthesia as much as women and

children.

Both military and civilian surgeons performed

surgical anesthesia for amputations more than for

any other type of operation, considering it more

humane. Many mid–19th-century surgeons believed

that surgical anesthesia killed about 5% more patients than operations without anesthetics.10(p220)

Contemporary statistics retrieved later proved this

conclusion incorrect: infection from industrial injuries probably caused deaths that were originally

attributed to the anesthetic in operations on seriously injured persons. Still, in the 19th century,

surgeons practiced selective anesthetization. They

wished “to balance life saving and painkilling, the

need to reconcile a universal science with human

variability.”10(p238)

The American Civil War

Mid–19th-century attitudes about anesthetics

influenced who received anesthesia early in the

American Civil War (1861–1865). Soldiers were at

the mercy of military surgeons, who, as in the Mexican War, had almost total control over anesthetic

policy.10 By late 1862, however, the Union army

attempted to standardize and centralize anesthetization policy as part of an overall reorganization of

the medical service aimed at regulating treatment

regimens in general. On 30 October 1862, Jonathan

Letterman, Medical Director of the Army of the

Potomac, issued a circular letter that embodied a

hospital reorganization plan that recommended that

each of the 18 division hospitals appoint an assistant surgeon in charge of anesthesia. The circular

letter specified who would make the decisions but

not what those decisions would be. The individual

doctor could still use his own discretion about

anesthetization, “[b]ut the degree of centralization

instituted by Letterman almost certainly did serve

to minimize the extreme variations in military anesthetic use.”10(p183)

Letterman’s concern was propitious, considering the widespread use of anesthetics during the

Civil War. The army medical service reported employing surgical anesthesia in no fewer than 80,000

cases. Surgeons preferred chloroform 76%14(p887) of

the time, although a mixture of ether and chloroform, or ether alone, were popular in general hospitals. The average insensibility time for chloroform

was 9 minutes, compared with 17 minutes for ether

and chloroform and 16 minutes for ether alone.14(p896)

Because of its ease of induction and the small

amounts required, chloroform was the anesthetic of

choice for field surgeons, who were surrounded by

wounded soldiers in need of rapid relief.

Medical officers also liked the drug’s nonflammability, its sweet smell, and its tendency to produce less vomiting and excitability among patients.

Aware of its dangers—on occasion, patients inhaling the drug became convulsive and suffered cardiac arrest and sometimes liver damage—surgeons

were careful to place time limits on the administration of chloroform and to ensure that the patient

inhaled adequate amounts of air along with the

anesthetic. In cases of exhaustion resulting from

long-established injuries, when chloroform was

considered too dangerous to use, ether became the

preferred anesthetic agent.7,14,15

Despite the overwhelming use of anesthetics, the

North reported, for cases studied, only 37 deaths

due to the administration of chloroform; the South

reported 2. One Confederate doctor exclaimed:

“The safety of the substance was remarkable when

you consider how loosely it was used!”15(p95) The

Army Medical Department cited only 2 deaths from

ether and 2 from chloroform and ether. The practice

of cautious administration of anesthetics by surgeons of both armies may account for the good

safety record. However, that chloroform anesthesia

caused so few deaths in an era of little patient

monitoring is difficult to believe. Many anesthesia

deaths may have gone unrecorded or were incorrectly attributed to wounds. In March 1865, Surgeon General Joseph K. Barnes was sufficiently

troubled by anesthesia deaths that he ordered U.S.

Army surgeons to report on their experiences with

these agents.7,14,15

The mode of administration of ether, chloroform,

or a mixture of both remained quite simple during

the Civil War. In a technique known as the open

method, a liquid-soaked sponge, cloth, or handkerchief was placed over the patient’s nose and mouth.

For many operations in the open air, a funnel served

as an inhaler to prevent excessive evaporation.

Although less complicated than the elaborate systems used in modern gas anesthesia, the open

method was an effective and relatively safe mode of

achieving anesthesia on the battlefield.14,15

To prevent the waste of chloroform, a scarce

commodity in the South, Confederate surgeon J. J.

Chisolm employed a short, flattened cylinder with

a plate on its broadest side and two nosepieces
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863

connected to the cover. Chloroform dripped through

the plate of the Chisolm inhaler onto a sponge or

folded cloth, which offered a broad area for evaporation, inside the cylinder. The patient’s limpness,

a rough but nevertheless quite reliable signal, let

the surgeon know that the anesthetic was working

and surgery could commence. Often the soldier

received a premedication of whiskey to calm his

nerves and desensitize him, which also reduced the

amount of anesthetic needed.14,15 A few fearless

souls, who probably considered it cowardly to use

an anesthetic, “would simply lean back and let the

bloody operator saw away, telling the anesthetist to

save his sweet-smelling potion for those who came

in screaming.”15(p96)

For the alleviation of pain, army surgeons also

used analgesics such as alcohol and opiates. The

widespread use of alcohol to relax a patient before

the administration of an anesthetic caused some

medical officers to worry about the masking of

symptoms, but that problem never became significant during the Civil War. However, the possible

overuse of opiates, especially opium in the treatment of diarrhea, was blamed for the many cases of

drug addiction reported after the war. To reduce

pain, army physicians also administered morphine

and, on occasion, cannabis for tetanus and head

injuries.7

The supply of anesthetic agents during the war

remained more than adequate for the North but

just marginal for the South. The drug manufacturer

E. R. Squibb, the North’s chief supplier, had perfected the method of mass production of drugs at

Brooklyn’s U.S. Naval Hospital laboratory a few

years before the war started. Capturing medical

supplies also augmented stocks. Supply trains of

both sides got bogged down in mud or fell victim to

enemy raiding parties. For example, Stonewall

Jackson’s men ran off with thousands of cases of

chloroform at the Battle of Winchester. The South

often used this form of supply replenishment.15

Anesthesia came into its own during the Civil

War. Military surgeons demonstrated its usefulness beyond doubt and improved its safety

through the knowledge acquired from thousands

and thousands of administrations of ether and

chloroform.15

Late–19th-Century Advancements

During the latter part of the 19th century, surgical anesthesia advanced to include new administrative techniques, other drugs with special properties, and innovative machines for the delivery of

anesthetics. Closed inhalers, which had been improved since the Morton and Snow devices of the

1840s and 1850s, appeared in greater numbers.

Noteworthy was the J.T. Clover inhaler, which regulated the flow of the anesthetic with air or with

another anesthetic (Figure 31-7). Gardner Q. Colton

popularized the use of pure nitrous oxide in dental

operations in 1863. A mixture of nitrous oxide and

oxygen appeared in anesthetic practice and led to

the development of gas machines for surgical anesthesia. The latter were hardly used before World

War I.1–3

The development of the hypodermic syringe (Figure 31-8) permitted the use of morphine during

inhalational anesthesia and as a preanesthetic medication. The discovery of the anesthetic properties of

cocaine led to the use of the drug topically in eye

surgery, in nerve block anesthesia, by injection in or

around the spinal canal to reduce pain, and in the

first spinal anesthesia in man. (Spinal anesthesia

became generally used in the Vietnam War.) Ethyl

chloride became a local anesthetic agent late in the

19th century.1–3

William Stewart Halsted discovered conduction

anesthesia by injecting the new drug cocaine into a

nerve in 1885. The discovery’s drawbacks made it

controversial. Surgeons feared the lowering of blood

pressure, especially in seriously injured patients;

the psychic factor of the patient’s being aware of his

surroundings while undergoing surgery; and the

poisonous effect of the drug, which could be habitforming. With nerve block anesthesia as an option,

however, surgeons began to choose the anesthetic

to fit the patient rather than to select patients who

were fit for anesthesia. The mid–19th-century practice of selective anesthetization was nearly over.10,16

The greatest influence on the development of

anesthesia as a science was Joseph Lister’s discovery of antisepsis during the latter part of the 19th

century, which drastically reduced infection in surgery. Antisepsis and anesthesia together led to the

advancement of surgery by making surgery less

unhygienic and less dangerous. Also contributing

to clean surgery at this time was the acceptance of

the germ theory of disease in 1890, after developing

gradually from the 1860s. Rubber gloves and operating coats began to appear in the operating room

about 1900.17 According to historian Martin S.

Pernick:

The gradual adoption of antiseptic surgery also

helped end selective anesthetization.... The complex rituals of Lister’s technique virtually demanded that all patients be immobilized with anesthesia.10(p238)
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864

a

c

Fig. 31-7. (a) Joseph Thomas Clover, shown filling the

reservoir bag of his chloroform apparatus with an accurate mixture of 41⁄2% chloroform in air. (b) Clover’s

chloroform apparatus (ca 1860); the original is in the

Wellcome Medical Exhibit, Science Museum London,

England. A known quantity of chloroform was injected

with a syringe onto a warmed metal surface inside the

brass container (right). The concertina bag (left) was then

filled with air, which was blown into a 7.2-L bag (not

shown) with the chloroform. A large-diameter breathing

hose and mask were connected to the bag to complete the

nonrebreathing circuit. Dr. Clover is said to have given

7,000 anesthetics using 4

1⁄2% chloroform without a death.

(c) Clover’s chloroform apparatus (ca 1870); the original

is likewise in the Wellcome Historical Medical Museum.

The photograph shows the carrying case, folded reservoir bag made of impermeable material, hand bellows,

chloroform vaporizing chamber with graduated glass

syringe for injecting liquid chloroform, and connecting

tube reinforced with a wire coil to prevent kinking. In the

foreground, Clover’s facepiece with an inflatable rubber

rim, a feature that came into use with nitrous oxide

anesthesia (ca 1870), and the metal junction, which has

become detached from the filling tube and reservoir bag.

Photograph (a): Reprinted with permission from Sykes

WS. Essays on the First Hundred Years of Anaesthesia. Vol 3.

Edinburgh, Scotland: Churchill Livingstone; 1982: 133.

Sources for (b): (1) Sanson AE. Chloroform, Its Action and

Administration. London, England: Churchill; 1865: 187.

(2) Macintosh R, Mushin WW, Epstein HG. Physics for the

Anaesthetist. 3rd ed. Oxford, England: Blackwell Scientific Publishers; 1963. Photograph (b): Reprinted with

permission from Wellcome Trends in Anesthesiology.

1944;12(1):5. Photograph (c): Reprinted with permission

from Duncum BM. The Development of Inhalation

Anaesthesia With Special Reference to the Years 1846–1900.

London, England: Oxford University Press, The Wellcome

Historical Medical Museum; 1947: 246.

b
A Brief History of Military Anesthesia

865

Fig. 31-8. Alexander Wood’s syringe, which is displayed in the Royal College of Physicians in Edinburgh, Scotland.

Intravenous anesthesia could not have been developed without the syringe, although Wood himself used his syringe

to deliver anesthetic locally, not intravenously. His 1855 paper was titled A New Method of Treating Painful Neuralgias

by the Direct Application of Opiates to Painful Points. Photograph: Reprinted with permission from Dundee JW, Wyant

GM. Intravenous Anaesthesia. Edinburgh, Scotland: Churchill Livingstone; 1988: 1.

beneficial that after the war, in 1901, they were

organized into a female nurse corps under former

contract nurse Dita H. Kinney.19–21

For surgical patients not seriously enfeebled by

disease, chloroform administered by the drop

method was the anesthetic of choice. (Drop chloroform was also used extensively during the Boer War

[1899–1901] and the Russo-Japanese War [1904].)

Soldiers considerably weakened by tropical ailments

received ether, which was less potent and slower in

onset of action than chloroform and therefore presumably less dangerous in the sick patient. During

operations to incise and drain abscesses, surgeons

preferred to work without an anesthetic, using only

whiskey to relax the patient.19

Surgical procedures that posed great danger to

the patient were avoided whenever possible. Bullets were allowed to remain in the body undisturbed unless they could readily be removed without additional risk. Some patients with penetrating

wounds of the chest and abdomen did well without

surgery. Conversely, to save the lives of patients

suffering from empyema, surgeons opened chest

cavities and extracted pus. A day or two before the

operation, they aspirated the patient’s pleural space

to achieve partial pulmonary expansion before admitting air into the pleural cavity. They preferred

to perform the surgery under partial anesthesia,

using strychnia and alcohol to minimize the dangers of the anesthetic. In most cases of surgery for

empyema, the patients completely recovered.19

Surgeons supervised other medical officers and

corpsmen in the administration of anesthesia, as the

discipline was relatively young and had few specialists. Antisepsis and conservatism helped to

make surgery successful during the Spanish–American War.19

Although by the turn of the century individual

practitioners with special skills were specializing,

particularly in the new aseptic surgery—even naval

hospitals at this time had the post of supervising

The almost universal practice of painless surgery

eliminated objections to women becoming surgeons

and operating room nurses. In the 1880s, increasing

numbers of female personnel began administering

anesthetics, under the guidance of surgeons. In the

following decade, the U.S. Army had no objection to

female nurses working alongside military surgeons

in the care of the wounded.10

By 1902, both the army and the navy opened

graduate schools of military medicine, where military surgeons studied the new science of bacteriology and sanitation mainly for public health work.

Graduate medical education outside of the military

at this time focused on learning specialized fields,

such as antiseptic and aseptic surgery. Modern

internship programs were just beginning in the

major hospitals in Britain.18

The Spanish–American War

Antisepsis, of course, played an important role in

the Spanish–American War, which was fought in

the Caribbean and the Philippines at the end of the

19th century. During this conflict, antisepsis reduced the four greatest enemies of the wounded

soldier: hospital gangrene, secondary hemorrhage,

pyemia, and erysipelas. If the wounded survived

the immediate effects of the injury—the explosive

force of the small-caliber bullet had been greatly

overestimated—the prospects of recovery were

good.19

Actually, military surgeons performed fewer

operations and administered less anesthesia per

capita during the war with Spain than during the

American Civil War. There were no stacks of amputated limbs as there had been during the Civil War.

Tropical diseases, such as malaria and yellow fever,

were the great killers during the Spanish–American

War. To assist an inadequate number of skilled and

trained medical officers, the medical department

hired female contract nurses. Their help proved so
Anesthesia and Perioperative Care of the Combat Casualty

866

surgeon—no formal courses existed in anesthesia.

Anesthesia providers were usually medical students, interns, or nurses in metropolitan hospitals,

and family practitioners in rural hospitals. They

learned to administer anesthesia through observation or from gas machine manufacturers, who would

teach the art to anyone who would buy a machine.18,22

On the eve of World War I, however, several

hospitals in the United States offered to physicians

6 months of postgraduate courses in anesthesia,

including instruction in anatomy, physiology of the

respiratory tract, pharmacology of anesthetic agents,

and training in the administration of the commonly

used drugs. For nurses, several hospitals offered

courses in the administration of anesthetics, lectures by physicians, and work on cadavers, including the passing of laryngeal tubes.18,22 Hospital

curricula reflected the growing interest in anesthesiology as it was about to enter an important era of

its development.

World War I

While still an uncertain science, anesthesiology was forced prematurely into service in World

War I (1914–1918). Military anesthesiologists

Frederick Courington and Roderick Calverley described the state of the art of anesthesiology in 1914:

Anesthesia machines were new and hardly widely

accepted. There was no standardization of equipment; nothing fit together. Bottled gases were available but miserably cumbersome. Continuous-flow

anesthesia with quantification of gas flow was

scarce. Wire screen vaporizers, with names like

Schimmelbusch, were simple, available, cheap, and

“good enough.” There were other vaporizers, but

most were little improved since the time of Joseph

T. Clover, 50 years before the war. Airways were

sometimes available, but endotracheal intubation

meant that a small, cuffless tube was inserted into

the trachea through the glottis for insufflation of

ether. Oxygen enrichment of air was uncommon.

Nitrous oxide, known in England as “gas” and

almost unknown in Europe, was frequently given

in various pseudoscientific asphyxial mixtures.

There were no muscle relaxants, nor was there an

understanding of controlled ventilation or of the

need for it. Venipuncture was a surgical cutdown.

Rational fluid therapy would not become routine

for decades, while blood transfusion was a near

perfunctory act, rarely used. Trauma and shock,

the unavoidable ingredients of war, were not understood, and therefore not effectively treated. Sir

Frederick Hewitt had published a major text of

anesthesia in England by 1893, and Dr. James Tayloe

Gwathmey, a prominent New York anesthetist,

published the first comprehensive American anesthesia text in 1914.23(pp642–643)

The American Journal of Surgery produced the first

Quarterly Supplement of Anesthesia and Analgesia in

October 1914, 2 months after the war in Europe

started.23

Personnel

At the start of hostilities in 1914, few anesthesia

providers were available to serve on the western

front, and anesthesia was often left in the hands

of inexperienced people. Early in the war, nonspecialty-trained medical officers in the British casualty clearing stations, located at least 7 miles

behind the front line and where initial surgery took

place, administered anesthesia, often unsuccessfully. One British anesthesiologist remarked: “The

bulk of preventable deaths at a casualty clearing

station was due to improper anesthesia, giving the

wrong anesthetic or giving the right anesthetic

wrongly.”24(p103)

To keep anesthesia out of inexpert hands, the

British army appointed anesthesiologists to clearing station staffs in 1916. Even those proved too few

to handle the casualties of an enemy push or offensive. After the Battle of the Somme in September

1916, one clearing station received 17,000 stretcher

cases and experienced 700 deaths. A Canadian

anesthetist lamented the lack of trained anesthetists

at this battle:

In a severe action, a [casualty clearing station] is

very busy and I cannot imagine any place where the

services of a skilled anesthetist would be more

useful. A [casualty clearing station] cannot, however, afford to have too much cumbersome apparatus as when the army moves, it moves too. We had

four operating tables going simultaneously. One

day we had over 70 operations. A few days before

we had admitted 760 wounded within 24 hours.

There were a great many severe chest wounds.23(p644)

Responsibility for anesthesiology during the

Great War rested mainly with reserve officers (both

Allied and American) who came from civilian medicine into the armed forces for the duration of the

war. Men like George Crile, a surgeon from the

Cleveland (Ohio) Lakeside Unit, who volunteered

to help the British Expeditionary Forces in France

before the United States entered the war. He established an American Ambulance Hospital in Neuilly,

bringing his own supplies and trained civilian nurse
A Brief History of Military Anesthesia

867

anesthetists with him. He and most of his staff

served in the U.S. Army once the United States

entered the war in April 1917. Dr. Crile helped

shape the practice of surgery and anesthesiology

during World War I.

In anticipation of the United States’ entry into the

war, the U.S. Army and the U.S. Navy appointed

their first anesthesiologists (physician anesthetists)

to the Medical Corps in 1916, with the rank of

lieutenant. In April 1917, the army drafted dentists

for anesthetic service, contracted for women physician anesthetists, and brought in nurse anesthetists

to serve at base hospitals in England and France.

They joined nurse anesthetists at American Ambulance Hospitals, such as the one run by Dr. Crile at

Neuilly. Those women inspired the British army to

train over 200 nursing sisters in anesthesia for service in France in 1918. The U.S. Army sent its own

nurses to schools of anesthesia that had developed

in the United States in response to the demands of

war. After training, they returned to their bases to

instruct others in anesthesia. (No records are available on the number of nurse anesthetists in the army

during the war. On 11 November 1918, the U.S.

Army Nurse Corps reached 21,480 nurses: 3,524

were regular nurses and 17,956 were reserve

nurses.22(pp22–23)) To provide more anesthetists, Dr.

Arthur Guedel, a physician anesthetist in charge of

anesthesia for the U.S. Army, made daily rounds to

base hospitals in the war zone, giving instruction in

anesthesia. He administered open-drop ether at

field hospitals, commuting between them by motorcycle. Guedel wrote a fundamental guide to

inhalational anesthesia in 1937.22,23,25,26

To produce skilled combat surgeons, in 1918 the

U.S. Army Medical Department’s Division of Surgery arranged with some of the nation’s finest medical schools to have medical officers receive intensive instruction in war surgery, including the

treatment of wounds and the administration of anesthetics. Schools in New York; Boston, Massachusetts; Philadelphia and Pittsburgh, Pennsylvania;

Chicago, Illinois; Cleveland, Ohio; New Orleans,

Louisiana; and Rochester, Minnesota, participated

in the program. On their return to army camps, the

medical officers who took the courses instructed

others in war surgery and anesthesia.27

Despite those efforts, there were never enough

experienced anesthesia providers at the front. A

nurse anesthetist, who administered anesthesia from

June to November 1918, at a U.S. Army mobile

hospital in the Chateau-Thierry area of France, recalled:

How many anesthetics I gave during the World

War, I cannot determine, except that when the big

drives were on, lasting from a week to ten days, I

averaged twenty-five to thirty a day.... During the

drives patients came in so fast that all the surgeons

could do was to remove bullets and shrapnel, stop

hemorrhages and put iodoform packs in the wound

and bandage it. As soon as they were through

operating on one patient, I would have to have the

next patient anesthetized.22(p24)

Another anesthetist, who treated 34 cases in 1 day,

recalled: “While one patient was being operated on,

another was being prepared for surgery, as the

dressing was being applied to the third.”23(p645) The

operations during those drives were of necessity

quick, deft, and light.

Equipment

Anesthesia providers needed to bring to the front

supplies that were mobile and adequate for mass

casualties. They also wanted to give the best anesthesia possible. Those wishes were usually contradictory, because the best anesthesia machines were

often cumbersome and not easily transportable,

and required experts to operate. Additionally, early

in the war, certain machines, anesthetic equipment,

and agents, as well as skilled anesthetists, were in

short supply. For example, in 1917, the army’s list

of anesthesia supplies included ether, chloroform,

and ethyl chloride only—but no anesthetic equipment.23 World War I anesthetists, like medical men

in every war, had to “make do,” given the logistical

constraints and the newness of the specialty.

The first anesthetists to feel the pinch were those

of the British armed forces, who had been fighting

since 1914. At the outbreak of war, these men had

only chloroform and simple wire vaporizers known

as the Schimmelbusch mask (Figure 31-9). Within a

few months, ether became available, which they

administered by the open method. In 1915, a Canadian medical team brought to England the new

Ohio Monovalve anesthesia apparatus, which, unlike British machines, provided a steady flow of gas

at a uniform pressure (Figure 31-10).23,28

In 1916, the new Shipway ether/chloroform apparatus, although not as advanced as the device

from North America, became available. The machine of Dr. Francis Shipway, a British anesthetist,

consisted of two bottles, one for chloroform and one

for ether, and a three-way tap, which allowed air to

be blown through one bottle at a time or through

both in varying proportions as one wished. A tube
Anesthesia and Perioperative Care of the Combat Casualty

868

from the device passed through a lint mask or

directly into the patient’s mouth or nose. The

Shipway apparatus provided even and light administration of the anesthetic and was superior to

the drop method. With the advent of the Shipway

machine, warm ether vapor became the British anesthetic of choice when nitrous oxide and expert gas

administrators were unavailable.23,28 Shipway’s nitrous oxide/oxygen/ether apparatus became available in 1920 (Figure 31-11).

For American anesthetists, the U.S. Army adopted

the American Red Cross’ nitrous oxide–oxygen

machine, perfected by Captain James T. Gwathmey,

an anesthetist from New York and a reserve officer

who served on the western front (Figure 31-12).

Gwathmey’s machine provided an airtight mask

that fitted closely to the face, an escape valve, a

mixing bag close to the inhaler, and a rough gauge

for measuring the proportion of the gases. Like the

British army, the U.S. Army on the western front

had gas machines but little nitrous oxide until a

nitrous oxide plant from Cleveland, Ohio, opened

in France in mid-1918, just a few months before the

war ended. Dr. Crile, a great advocate of the use of

gas, had, of course, brought his own supply with

him to France. When nitrous oxide was unavailable, the Americans used ether, chloroform, or ethyl

chloride, in that order.29 Logistics became a determinant in the delivery of combat anesthesia.

Anesthetic and Delivery Method of Choice

Since Halsted’s discovery of conduction anesthesia

in the 1880s, surgeons had begun selecting the anesthetic agent and method of delivery that suited the

patient’s condition and the type of surgery he needed.

This reasoning prevailed at the second session of the

Inter-Allied Surgical Conference, held in Paris in 1917.

Fig. 31-10. The Ohio Monovalve anesthesia machine, an

advanced apparatus from North America, with its continuous flow, multiple gases, and heated vaporizers, also

became popular in Europe early in World War I. Photograph: Reprinted from Gwathmey JT. Anesthesia. New

York, NY: Appleton; 1914.

Fig. 31-9. The Schimmelbusch wire frame mask (ca 1890),

the most widely known of all wire frame masks, was

developed by Carl Schimmelbusch (1860–1895), a surgeon in Berlin, Germany. The lower rim of the mask,

which collected surplus anesthetic liquid, is curved to

allow air to be drawn under it during chloroform administration. With padding, this wire mask could be used for

ether administration. Source: Thomas KB. The Development of Anaesthetic Apparatus. Oxford, England: Blackwell

Scientific Publications; 1975: 252. Photograph: Reprinted

with permission from the Charles King Collection of

Historic Anaesthetic Apparatus (Colour Slide Collection), Association of Anaesthetists of Great Britain and

Ireland, London, England.
A Brief History of Military Anesthesia

869

Fig. 31-12. Gwathmey’s nitrous oxide/oxygen/ether apparatus (1913). This early apparatus utilized, for the first

time in anesthesia, the water-sight flowmeter manufactured by Cotton and Boothby in 1912. The ether bottle is

missing in this example of the apparatus, which shows

only the flowmeter and cylinder yokes. Source: Thomas

KB. The Development of Anaesthetic Apparatus. Oxford,

England: Blackwell Scientific Publications; 1975: 139–

142. Photograph: Reprinted with permission from the

Charles King Collection of Historic Anaesthetic Apparatus (Colour Slide Collection), Association of Anaesthetists

of Great Britain and Ireland, London, England.

Fig. 31-11. Shipway’s nitrous oxide/oxygen/ether apparatus (1920), a modification of earlier equipment, could

be used in the draw-over mode if gases were unavailable

by means of extra inlets into the ether jar and a complex

control tap. Source: Thomas KB. The Development of

Anaesthetic Apparatus. Oxford, England: Blackwell Scientific Publications; 1975: 152–153. Photograph: Reprinted

with permission from the Charles King Collection of

Historic Anaesthetic Apparatus (Colour Slide Collection), Association of Anaesthetists of Great Britain and

Ireland, London, England.

The conference’s conclusions about choice of anesthetic and treatment for war injuries confirmed the

value of nitrous oxide in military surgery:

• Treatment of gaseous gangrene. Anesthesia by

means of nitrous oxide with oxygen is considered the best; when this is not to be had, ether

may be substituted.

• Traumatic shock. Local anesthesia combined with

general anesthesia by means of nitrous oxide is

the best. Next to this ether appears to be the least

harmful. Spinal injections have produced varying results according to the surgeons employing

them, especially in amputations of the lower

limbs. The use of chloroform is dangerous.

• Amputations. In the case of serious shock, the use

of nitrous oxide and oxygen is desirable; ether is

the next best anesthetic. Only in the case of

cerebral wounds is any other anesthetic method

advised.

• Cerebral wounds. Local anesthesia is preferred

for the operation. The sitting posture tends to

diminish hemorrhage and is easily maintained

in secondary or delayed operations.29(p166)

Allied armies, in general, followed the conclusions

of the Paris conference of 1917.

Although healthy men with light wounds could

receive any of a number of anesthetics, military

surgeons in World War I preferred the advantages

of nitrous oxide mixed with oxygen, when they

could get it. The British considered the mixture,

in experienced hands,...the ideal anesthetic for such

patients, since it fulfilled the three essential conditions—safety, speed, and a rapid recovery. [The

last permitted] immediate evacuation by ambulance and train.28(p182)
Anesthesia and Perioperative Care of the Combat Casualty

870

But the ideal method was often unrealistic. Although the gas was beginning to become popular, it

was not manufactured in great quantities. Hence,

the short supply of nitrous oxide and of skilled

administrators until late in the war led the British to

use warm ether vapor more than any other anesthetic. For lightly wounded men, the French preferred ethyl chloride because of their “need to induce quickly, perform minimal surgery and

transport [patients] sitting up in ambulances.”23(p650)

A vehicle could transport more casualties who were

sitting rather than lying down. When the agent of

choice was unavailable, the anesthetist made a

judicious substitution of another drug and

method.23,28

For chest surgery, U.S. Army anesthetists chose a

light nitrous oxide–oxygen analgesia combined with

local anesthesia. Using the results of animal experimentation and accounts from surgical teams at the

front, Captain Gwathmey, working out of the U.S.

Army’s medical research laboratory in France, devised an effective anesthesia for chest surgery. Using

a full preoperative dose of morphine to produce

analgesia, he gradually

administered 3:1 nitrous oxide and oxygen under

5–7 mm continuous positive pressure with a mask,

adding light ether as required.23(pp649–650)

. . . .

During the operation, the proportions of the gas–

oxygen mixture and the pressure transmitted to the

trachea were varied to meet conditions.29(p179)

The Gwathmey method permitted intrathoracic

surgery “without necessitating deep anesthesia for

the introduction of intratracheal or endopharyngeal tubes.”29(p179) Although greatly improved anesthesia permitted lifesaving thoracic surgery during

World War I, chest surgery remained hazardous for

all patients and, in general, “...anesthesia contributed significantly to surgical mortality.”23(pp649–650)

For thoracic surgery, British anesthetists, in most

cases, used chloroform or ether and oxygen with the

Shipway apparatus. If the patient was of a placid

temperament and sufficiently under the influence

of morphia or omnopon, a few surgeons used “local

infiltration combined with the administration of

gas and oxygen.”28(p183)

For abdominal operations, both American and

British military surgeons established that regional

anesthesia with novocaine to relax the abdominal

muscles followed by general anesthesia with nitrous oxide–oxygen produced the best results. Warm

ether vapor was the accepted substitute for nitrous

oxide in those operations.28,29

Military surgeons also found nitrous oxide–oxygen, if properly administered, to be the best anesthetic for major amputations. When the gas was not

available, surgeons substituted low spinal anesthesia, sometimes with a blood transfusion to overcome the anesthetic’s tendency to lower the blood

pressure.28,29

For operations on the severely wounded in shock,

expert anesthetists, including many from the U.S.

Army Nurse Corps, administered nitrous oxide–

oxygen in the ratio of not more than 3 parts gas to

one part oxygen to avoid deep anesthesia and

cyanosis. (Future anesthetists would consider even

this ratio too dangerous.) A higher ratio might have

caused as great a fall in pressure as was produced

by ether. When nitrous oxide was unavailable and

ether was substituted, sometimes a blood transfusion or a gradual infusion of a gum–salt solution (“6

to 7 percent of gum acacia in 0.9 percent sodium

chloride”30(p194)) accompanied ether administration

for patients in shock to maintain or even raise the

head of arterial pressure. Intravenous fluids or

blood plasma did not receive widespread use, however, and physicians considered some hypovolemic

patients simply inoperable.28,30

For gassed patients, anesthesia providers preferred nitrous oxide–oxygen. But if the anesthetic

was not available, medical personnel used local,

regional, or spinal anesthesia. Ether irritated the

respiratory tracts of patients exposed to chlorine

and other gases and was seldom used. Both British

and American armies found that patients who had

been gassed gave no special problem on the operating table.28,29

The Allies had differing opinions about the value

of spinal anesthesia during World War I. Dr. Crile

thought that spinal anesthesia was of value in all

but rush periods, provided that the psychic factor of

the wide-awake patient was eliminated by partial

anesthesia, either morphine or light nitrous oxide,

and that the fall in blood pressure was prevented by

a blood transfusion. Most British surgeons did not

favor spinal anesthesia because of its danger to

hypovolemic or hemorrhaging patients. One French

surgeon strongly advocated spinal anesthesia for

all surgery below the 10th thoracic nerve. Most

surgeons agreed that spinal and local anesthesia

were preferred methods when respiratory disease

made inhalational anesthesia difficult.23,28,29

Regarding local anesthesia, a survey of base hospitals in France by the American Red Cross, which
A Brief History of Military Anesthesia

871

was in charge of medical research for the American

Army, revealed that anesthesia providers recommended local anesthesia in combination with morphine whenever possible. The technique suited the

demands of war surgery, especially during “rush

periods at the front”29(p175) when nitrous oxide–oxygen was unavailable and little time existed for the

prolonged induction and recovery periods that normally followed the administration of ether or chloroform. Infiltration with novocaine was in common

use alone or in combination with nitrous oxide–

oxygen.28,29

Blood Transfusions and Other Treatments for Shock

Although the condition of shock had been known

to military surgeons for 300 years, its causes, onset,

and development remained a mystery. During

World War I, British medical officers in the field, in

conjunction with members of the Wound Shock

Committee of the Medical Research Committee,

studied the problem. American scientists, under

the auspices of the National Research Council and

the U.S. Army Surgical Research Laboratories, investigated shock during the war. Walter B. Cannon,

U.S. Army Reserve officer and physiologist from

Harvard University, studied shock and resuscitation with American and British forces in France and

England and became a member of the British Shock

Committee in 1917. He and allied scientists shared

research findings and results in investigating the

mysteries of shock.31

Cannon focused on treatments for shock when he

became the director of a center for surgical research

at the Central Medical Department Laboratory of

the Army Expeditionary Force at Dijon, France, in

1918. He maintained a close relationship between

the laboratory and the proving ground by establishing a network of resuscitation teams to treat soldiers in shock on or near the battlefield.

From May to November 1918, medical officers

received instruction at weekly classes in Dijon on

the nature of shock, onset theories, clinical symptoms, development circumstances, and treatment

beliefs. They mastered methods of matching blood

and giving blood transfusions. These officers went

from the classroom to the shock wards at U.S. Army

hospitals, where the seriously wounded received

blood transfusions and other treatments in preparation for surgery later.22,30–32

The importance of blood volume in the treatment

of shock was revealed during World War I. Medical

officers had reported that “in cases of profound

shock accompanied by loss of blood, excellent results are obtained from direct blood transfusion.”33(p42) Because of the difficulties of giving

transfusions at clearing stations during an attack,

Captain (later Major) Oswald H. Robertson, U.S.

Army, favored the collection, storage, and preservation of whole blood.34 At his suggestion, small

quantities of liquid blood had actually been preserved and transported considerable distances up

to regimental aid posts. The addition of new red

blood cells were, in Robertson’s opinion, “the only

means available of increasing the oxygen-carrying

power of the blood....[T]his constitutes the unique

value of blood transfusion.”33(p42)

Robertson was a pioneer in establishing the concept of the world’s first blood bank. He joined

Cannon at the surgical research laboratory in Dijon,

France, in August 1918, where he helped untangle

the problem of “the efficacy of using gum acacia in

the treatment of shock.”31(p243) He concluded that

there was an absence of convincing data as to gum

acacia’s usefulness in the treatment of shock.

At the end of World War I, William M. Bayliss, a

distinguished British physiologist who had served

on the Wound Shock Committee of the Medical

Research Committee during the war, regretted “that

so little positive evidence is forthcoming as to the

superiority of blood transfusions. Statements are

made on the basis of general impressions, rather

than on convincing proof....”33(p347) Without convincing data, medical authorities might underestimate the importance of blood transfusions in the

treatment of shock after the war.33

Also, the World War I Shock Committee’s attempts to study shock were generally unsuccessful

and led to fallacies. For example, the Committee

had concluded at the end of the war “that the

absorption of toxins from injured tissues was the

primary cause of traumatic shock.”35(p29) That belief

led to misconceptions about the relationship of

muscle injury to shock in the postwar years. Little

progress was made on the relation of anesthesia to

the development of shock. The Committee’s great

achievement, however, was in giving recognition to

the complex problem of wound shock.

Other treatments for shock during World War I

included restoration of lost body heat by surrounding the patient with blankets; injection of morphia

to reduce pain and restlessness; and the return of

blood from the large veins of the abdomen to the

heart by raising the foot of the bed, a practice used

for years in civilian hospitals, to permit gravity to

aid the blood’s return. Shock ward officers re-
Anesthesia and Perioperative Care of the Combat Casualty

872

ported that the technique had no marked effect on

either systolic or diastolic pressure. They also observed that the use of vasoconstrictor drugs to improve circulation in shock was futile, as clinical and

experimental observations showed that the heart

was not primarily affected in shock.30

Aftercare in World War I shock wards included

monitoring of the patient’s blood volume until it was

restored to the normal level, a difficult procedure

under field conditions, and the provision of fluids by

either mouth or rectum until the urinary output

equaled the water intake. Although military physicians stressed the need to watch for unfavorable developments and to treat them accordingly, postoperative care was not well developed in World War I.30

Despite its limitations, treatment of the seriously

wounded during the war produced valuable lessons about shock and resuscitation. Cannon observed30 that

• shock wards required two resuscitation

teams, each consisting of a medical officer,

a nurse, and an orderly;

• withdrawing 500 to 750 mL of blood did the

slightly wounded man no harm, and saved

the life of a soldier suffering from shock or

severe hemorrhage;

• in preparation for shock cases, resuscitation officers needed to provide heating arrangements, transfusion equipment, and

blood donors (and to determine their blood

grouping); and

• resuscitation officers needed to perform or

direct transfusions, give the surgeon their

judgment of the optimum time for surgery,

and do clinical work for the surgeon—so

long as this work did not interfere with the

resuscitation officer’s important duties in

the shock ward.

After a rocky start, military anesthesia greatly

developed during the war to the benefit of the

patient, the surgeon, and the war effort. For the first

2 years of the conflict, military anesthesia sorely

lacked trained providers, advanced equipment, and

supplies of nitrous oxide. Many soldiers’ lives

might have been saved had this not been the case.

During the last 2 years of the war, the availability of

improved apparatus, the employment of expert

anesthetists, and the administration of warm ether

vapor or nitrous oxide–oxygen instead of chloroform, whose potency could become dangerous,

undoubtedly saved many lives.

Reserve officers from civilian medicine, who

served as consultants to the armed forces, preferred

nitrous oxide–oxygen anesthetic for most operations. The realization that this anesthetic required

expert administration emphasized the need for

trained anesthetists in the armed forces. As a result,

the armed forces sent officers to study war surgery

and anesthesia at medical schools throughout the

country and nurses to schools of anesthesia that

had developed in the United States in response to

the demands of war. However, most of those students never made it overseas, as the war ended

shortly after the buildup of American hospitals had

begun.

Valuable information on the treatment of shock

and resuscitation was produced during World War

I, but the complex problem of shock remained

shrouded in mystery. Nevertheless, the recognition of anesthesiology as a special field increased, as

did the recognition of the anesthesia provider as a

specialist rather than a technician. In 4 years, the

state of the art of anesthesiology had vastly improved.29 However, although anesthetists, like other

specialists, found a home in the armed forces, decades would pass before the institution of residency

programs in the U.S. Army.

After World War I, Dr. Crile wrote the chapter on

anesthesiology for the official medical history of the

war. His knowledge about anesthesia during the

war led him to conclude29 that

• nitrous oxide–oxygen, a light anesthetic,

was the preferred anesthetic for the patient

in shock; its administration required expert

handling;

• in cases of profound exhaustion, spinal

anesthesia would cause no serious fall in

blood pressure if the patient first received

an ordinary transfusion of blood;

• the psychic factor of being aware of the

operating room and staff might be overcome by morphine or very light nitrous

oxide anesthesia, or by light partial ether

anesthesia; and

• ether, on the other hand, caused pneumonia in abdominal cases during the winter,

was unsuitable in infections, and had a

tendency to cause a fall in blood pressure

after the operation; hence, ether should not

be used in cases of shock.

Whether 20th-century medicine would substantiate these revelations remained to be seen.
A Brief History of Military Anesthesia

873

Between the World Wars

The experiences of anesthesia providers in the

Great War helped shape the revolution in anesthesiology that occurred during the 1920s and 1930s.

As a result of the contribution of nurse anesthetists

during the war, nurse anesthetist programs grew

in number in both civilian and military medicine. Veteran physician anesthetists used their organizational skills and medical expertise to convince hospital personnel, mainly surgeons, across

the country to establish divisions of anesthesia. As

a result, departments of anesthesiology with residency programs began to appear. In 1939, the

medical department of the U.S. Army began formal

training of physicians in anesthesiology, one officer

at a time, while increasing internships and postgraduate education in specialties in general. On the

clinical side, transfusions, fluid therapy, intravenous anesthesia (revolutionized by the appearance

of the barbiturates, especially pentothal, which is

now known as sodium thiopental), and rebreathing anesthesia machines became more common (Figure 31-13).1–3,22,36,37

Anesthesiology grew as a profession during this

period. Physician anesthetists founded the American Board of Anesthesiology in 1937 as an affiliate

of the Board of Surgery and as an independent

board to pass on the qualifications of trained anesthetists in 1941. The American Society of Anesthetists, a physician organization, grew out of the

New York Society of Anesthetists and later became

the American Society of Anesthesiologists. The

American Association of Nurse Anesthetists,

founded in 1931 to help guide the education of

nurses in anesthesia, enhanced its power and helped

cement the rivalry between nurse anesthetists

and physician anesthetists, which had begun in the

1920s. Shortages of physician anesthetists meant

that nurse anesthetists dominated most medical

departments. New journals and books on anesthesia appeared in Europe and the United States,

and an exhibit on anesthesia opened at the 1939

New York World’s Fair. The roots of modern anesthesia were firmly planted between World War I

and World War II.36,37

Other developments during this period included

new techniques and agents. The improvement of

the soft metal needle made continuous spinal anesthesia possible by permitting the use of very small

doses and eliminating concern over the wearing off

of the anesthetic. The endotracheal catheter, developed by British plastic surgeons Ivan Whiteside

Fig. 31-13. This rebreathing anesthesia machine, made in

1918, was offered to the US Army in June 1918. Photograph: Reprinted with permission from Jackson DE. Anesthesia equipment from 1914 to 1954 and experiments

leading to its development. Anesthesiology. 1955;16:962.

Magill and Edgar Stanley Rowbotham for use on

wounded World War I veterans, gave anesthetists

“direct control of the respiratory tract and its

contents”1(p286) and provided the surgeon a quiet

field in which to work. The combination of the new

technique with the new anesthetic cyclopropane

enabled the anesthetist to “synchronize the movements of the lung with the work of the surgeon.”1(p286)

In the search for the ideal anesthetic, divinyl

oxide, a cross of ether and ethylene (an anesthetic

that was fast in action but weak), appeared. By

producing a rapid and brief anesthesia, divinyl

oxide, later replaced by sodium thiopental, put the

patient to sleep before the ether was administered,

rendering ether more pleasant. New anesthetics

like Nembutal and the barbiturates—evipan and

sodium thiopental—administered by the intravenous route came rapidly into favor. Man improved
Anesthesia and Perioperative Care of the Combat Casualty

874

or produced machines for the administration of a

variety of anesthetics. Those developments boded

well for the future of anesthesia.

The development of the carbon dioxide–absorption technique made possible modern and efficient

gas anesthesia machines (Figure 31-14). This

technique permitted the patient to receive measured amounts of anesthetic gases and oxygen by

adding ether to the mixture in small doses until the

desired level of anesthesia was achieved. Expired

gases passed through a soda lime canister that absorbed carbon dioxide before the gases entered a

rebreathing bag, and the patient, on impulse,

breathed in a warm blend of vapor and oxygen or of

gases and oxygen. The containment of all gases in

a closed circuit greatly reduced the chance of fire as

well as the cost of anesthesia, since enclosed agents

were not likely to escape. This technique also enabled the anesthetist to manage the patient’s breathing and to maintain periodic positive-pressure anesthesia. This procedure was a boon to the

anesthetist on the eve of World War II.38

Shock therapy, however, which is best studied in

war, with its numerous casualties and major injuries, was an area that showed little improvement in

the interwar years. After World War I, shock study

took place in “experimental laboratories, in which

attempts were made to [analyze shock] by physiologic and chemical techniques under a wide variety of experimentally induced conditions.”35(p29)

Developments in shock therapy were understandably slow. The theory of toxemic shock persisted

until the late 1920s, when A. Blalock, E. Parsons,

and D. E. Phemister “demonstrated that shock produced by trauma to the limbs is not the result of

toxemia but of a local loss of blood and fluid and of

circulating blood volume.”35(p29)

N. E. Freeman and his associates concluded from

their observations “that the blood volume is a more

reliable index of shock than the blood pressure,”but

the misconception persisted that “true shock [is] a

generalized increase in capillary permeability.”35(p30)

Other fallacies also persisted, notably, that blood

plasma is as effective as whole blood in the treatment of shock. Also, no practical way of determining blood volume under field conditions was developed during the years between World War I and

World War II.

By 1940, the military, which had few medical

specialists of any kind, depended largely on civilian

medicine for specialized training of medical personnel and fulfillment of mobilization goals. Reserve medical officers and nurses entered the military in increasing numbers during the emergency

buildup of 1940 and 1941. Specialists like Henry

Swartley Ruth of the Philadelphia General Hospital

taught young military physicians the values, concerns, and ideas of civilian medicine. The military

started to respect specialization, accepting a civilian tenet that the “best care” for their patients

“meant specialized care.”18(pp7–8) The army took specialization into account when making assignments

during the war. The navy established residency

training in naval hospitals in 1944. Specialization

was fast becoming an important factor in military

medicine.18

World War II

Personnel

Even in World War II (1939–1945), however, there

were never enough trained anesthetists to meet the

needs of the military. At army hospitals in the

United States, nurses gave inhalational anesthesia,

while surgeons administered spinal, local, and regional anesthetics. At overseas theaters of operations, the military overcame shortages of skilled

personnel and provided assistants for periods of

peak loads by the continual training of nurse anesthetists, dentists, medical officers pressed into service, and corpsmen within the theater. Some dental

officers learned drop ether and spinal anesthesia.

Because surgery in forward-area hospitals taxed

intelligence, judgment, resourcefulness, and technical ability, the army made every effort to assign

its best-trained anesthesia providers to the combat

zone. Anesthetists rendered great service in the

Fig. 31-14. The To-and-Fro Absorber was introduced by

Ralph Waters, MD, in 1923 at the University of Wisconsin. Carbon dioxide–absorbent granules were placed in

the canister; the patient was allowed to breathe “to and

fro” through the canister. The device was accepted rapidly because it was simple and practical. Photograph:

Courtesy of Ohmeda, Inc., Madison, Wis.
A Brief History of Military Anesthesia

875

forward areas of the North African Theater of Operations, where shortages of trained and experienced anesthesiologists persisted through 1943. By

1944, two skilled anesthesiologists served in each

field and evacuation hospital sent to Europe, and

one on each auxiliary surgical team on the front line

(Figure 31-15).38–41

Anesthetics and Equipment

Shipping priorities and the need for simplicity at

the front limited the choice of anesthetics and machines that accompanied frontline medics overseas,

despite a wide range of agents and devices available at the start of the war. Combat anesthetists

needed to have agents that could be hand carried

and administered by improvised techniques and

equipment. A scarcity of trained personnel narrowed the choice of drugs to those that people with

limited experience could administer. Scarce shipping space and the need for forward-area hospitals

to move quickly prohibited the employment of cumbersome equipment. The complex anesthesia apparatus, such as delicately adjusted gas machines, ran

the risks of leakage and loss of serviceability due to

rough handling during movement on short notice.38

There was a need for portable gas machines in each

platoon of the highly mobile (300-bed) field hospib

a

Fig. 31-16. Portable anesthesia apparatus, McKesson

model 675, (a) packed in its carrying case and (b) assembled. Photographs: Reprinted from Anesthesia Apparatus, Portable (Item 9350000). Washington, DC: War Department; 1945: 4–5. Technical Manual 8-623.

Fig. 31-15. Anesthesia as it was administered during

World War II. Photograph: Courtesy of National Library

of Medicine, Medical History Section, Bethesda, Md.
Anesthesia and Perioperative Care of the Combat Casualty

876

tal or small (750- or 400-bed) evacuation hospital,

“where intermittent positive pressure was essential

for adequate care of nontransportables.”40(p600)

The army issued four types of portable machines

in World War II—the Ohio, McKesson, and

Heidbrink (affectionately known as the “pig”),

which were standard in civilian hospitals (Figures

31-16 and 31-17), and the Beecher machine, designed especially for active combat by Henry K.

Beecher, reserve medical officer and Anesthesia

b

Fig. 31-17. Portable anesthesia apparatus, Heidbrink

military model 685. (a) Upper half of storage case, (b)

lower half of storage case, and (c) unit assembled. Photographs: Reprinted from Anesthesia Apparatus, Portable

(Item 9350000). Washington, DC: War Department; 1945:

12, 13. Technical Manual 8-623.

c

a
A Brief History of Military Anesthesia

877

Consultant to the North African–Mediterranean

Theaters of Operation (October 1943–August 1945).

Light, compact, and easily hand carried, the

Beecher machine could develop positive pressure

in the airway without depending on tanks of oxygen, which were often unavailable at the front. Foot

bellows were dispensed with when oxygen was on

hand. The maintenance of a constant flow of room

air through the apparatus allowed the system to

continually flush, making the use of soda lime–

carbon dioxide absorbent unnecessary. The device

was encased in a compact container with enough

capacity to hold a laryngoscope; intratracheal tubes;

an aspiration bulb and catheter for emptying the

bronchi; a packet of an induction agent, normally

sodium thiopental; and two cans of ether, each

weighing 1 lb. A fully loaded container weighed 25 lb.

Although designed specifically to make thoracic

surgery possible without compressed air, the

Beecher machine proved useful in combat for inhalational anesthesia, the administration of oxygen,

and artifical respiration. This simplified machine

became the apparatus that anesthetists used most

often in World War II after mid-1944 and the buildup

for Normandy. Before then, portable machines

were in short supply, particularly in the North

African theater. In the absence of portable machines, anesthetists relied on agents and methods

that did not require movable devices, risking the

lives of some patients.25,38,39

U.S. Army anesthetists had a wide variety of

agents to choose from, including ether, chloroform,

ethyl chloride, nitrous oxide, sodium thiopental,

procaine, tetracaine hydrochloride, and cocaine.

Cyclopropane and ethylene also were on hand, but

military anesthesia machines were not equipped to

handle those flammable bottled gases under pressure in cylinders. Hence, they were not used in

combat.38

When machines were available, the choice of

anesthetic usually depended on the experience of

the anesthetist, the preference of the surgeon, and

the problems of surgery. Ether anesthesia combined with oxygen, following induction with nitrous oxide, became popular because of its simplicity of administration, ready availability, easy

tolerance by patients, and general safety. Ether’s

disadvantages, “irritat[ion] to the mucous membranes of the respiratory tract...[and] disturbance of

metabolism, the blood sugar frequently being elevated from 100 to 200 percent,”42(p69) were outweighed by its advantages, particularly its margin

of safety, since anesthetists were not equally trained,

experienced, and capable.

Ether became the preferred anesthetic for casualties who were seriously wounded or in shock, which

completely reversed the practice of World War I. By

1941, physicians knew that an impaired circulatory

system took prolonged ether anesthesia well and

that, according to Beecher, a man in shock tolerated

ether far better than an animal in shock. Since

trauma patients could take ether, then men less

badly off could also take ether. In the Mediterranean Theater of Operations, where U.S. troops had

been engaged in combat since November 1942, ether

was the preferred anesthetic in more than 90% of

cases.25(p182) In the European theater, inhalational

anesthesia was used 86.2% of the time in Seventh

U.S. Army field hospitals, compared to only 23.2%

of the time in their evacuation hospitals, where

fewer trauma cases were seen, and intravenous

anesthesia with sodium thiopental became the preferred method.39(p549)

Nevertheless, the scarcity of portable machines,

but more importantly, of fully experienced anesthesiologists, led to inexpert choices of agent and

method for patients in critical condition. In the

North African theater in 1943, for example, in the

interest of time, inexpert anesthesiologists used

spinal anesthesia or intravenous anesthesia with

sodium thiopental when the poor condition of the

patient dictated inhalational anesthesia. This trend

was increased by the shortage of anesthesiologists

trained in inhalational anesthesia using “carbon

dioxide absorption and intermittent positive pressure administered through an endotracheal

tube.”40(p603) Shortfalls of machines and skilled personnel led to substandard combat anesthesia.

Sodium thiopental, a popular anesthetic, proved

valuable as an induction agent preceding ether anesthesia of men in good condition, sometimes as an

adjunct to spinal anesthesia, and as a sole agent for

procedures of short duration. If the operation lasted

longer than 30 to 45 minutes, the anesthesia provider switched to ether. Sodium thiopental had the

advantages of being readily available; simply and

compactly designed; easily and smoothly induced,

even by inexperienced physicians; and with few

undesirable aftereffects, all of which made it a good

drug under combat conditions.

Medical personnel would not use sodium

thiopental on patients suffering from shock, an impaired intake of oxygen, severe hemorrhage, inflammation “in the region of the carotid body or

carotid sinus,”38(p72) gas gangrene, severe burns,

when the operative position interfered with the

airway or complicated artificial respiration, or

when intracranial surgery was required. Bad-risk
Anesthesia and Perioperative Care of the Combat Casualty

878

patients tolerated full barbiturate anesthesia poorly.

Hence, sodium thiopental was used more often at

evacuation hospitals, further back along the evacuation chain than in field hospitals, where more

shock cases were observed. In Seventh U.S. Army

hospitals, for example, intravenous anesthesia

with sodium thiopental was used 53.1% of the time

in evacuation hospitals and only 2.8% of the time in

field hospitals.39(p549) Surgical problems influenced

the anesthesia method chosen by combat medics.25,38,39

The medical department learned the hard way

about the danger of using sodium thiopental on

patients in shock. During the aftermath of the

attack on Pearl Harbor on 7 December 1941, a number of patients suffering from traumatic shock and

acute loss of blood experienced respiratory failure

and died as a result of sodium thiopental anesthesia

used intravenously. Those patients also did not

receive a transfusion of blood or gum-salt solution,

as the lessons of World War I regarding volume

resuscitation were lost to medical practice between

the wars. As a consequence of those deaths, anesthetists switched to open-drop ether, which proved

safer for patients in shock. Casualties attended to

later in Europe and the Pacific benefited from this

new appreciation of the risks of sodium thiopental

anesthesia on hypovolemic patients.43

A number of the other drugs supplied to the

army received limited use. Since civilian practice

discredited chloroform because of its intensely depressing effect on the circulatory system, it made

little sense to use chloroform on wounded men

suffering circulatory damage. Nitrous oxide became a routine induction agent but never the sole

anesthetic. Oxygen concentrations of 21% or 30% or

more always accompanied the gas. Ethyl chloride

became a satisfactory induction agent if administered cautiously. In World War II, unlike in World

War I, physicians understood the acceptability or

unsuitability of most anesthetic agents.25,38

Methods of Choice

Medical officers considered the best method of

anesthetic administration for military surgery to be

closed-circuit anesthesia, either the closed-circle

flow absorption method of the Heidbrink and

McKesson machines, or the closed to-and-fro absorption technique of the Beecher machine. This

system conserved body heat and moisture, maintained a high oxygen level while controlling the

carbon dioxide volume in the blood, preserved desired degrees of anesthesia, regulated respiration,

and maintained positive pressure. There was an

increasing use of the closed-system technique as the

war progressed.25

Although spinal anesthesia became an acceptable practice in World War I for wounds of the

extremities and pulmonary trauma, the method was

considered undesirable in World War II military

surgery for a number of reasons: the technique

caused a lowering of blood pressure in badly

wounded men suffering from trauma and loss of

blood, it made surgery lengthy and variable when

other casualties were waiting for attention, and it

allowed the undesirability of full consciousness in

an apprehensive casualty fresh from the battlefield.

Of 3,154 cases of abdominal injuries in the Mediterranean theater, anesthesia providers used spinal

anesthesia on 3 patients only, each one in good

condition and with minimal wounds.25(p185) Its limited use in combat reflected the belief that spinal

anesthesia was a poor choice for badly wounded

men at the front.25,38

Other regional or local anesthesia had limited

use in combat. Early in the war, the English found

that seriously wounded men tolerated poorly the

moderate discomfort and psychological trauma of

being conscious of their surroundings. The Allies

therefore used local anesthesia for minor surgery

on “easy-going” patients, who had exhibited a tolerance for occasional discomfort and other inconvenience. Local and regional block, normally with

procaine, proved useful in certain neurosurgical

and maxillofacial operations, but, in general, the

method was not practical because of the multiplicity of wounds in each patient.38,44 One anesthesiologist regretted not fully testing the combination of

local anesthesia with a light inhalational anesthetic,

which, he thought, might have had excellent potentialities in military surgery.25(p185)

Medical personnel performed topical anesthesia

with tetracaine hydrochloride or cocaine. They

used cocaine also for bronchoscopy or to ease a

difficult intubation. Endotracheal intubation occurred routinely in intracranial, maxillofacial, and

abdominal operations performed under general

anesthesia; in all thoracic operations in which the

pleura was involved; and in operations of more

than 1 hour.25,38

Shock Therapy and Resuscitation

The anesthesia provider played an integral part

in preoperative management, necessitating a knowledge of shock therapy and preanesthetic medication. Lessons of World War I regarding shock
A Brief History of Military Anesthesia

879

therapy and resuscitation were relearned, modified, and practiced in the North African theater by

April 1943. When the flow of casualties was heavy

and a shock team was unavailable, both anesthetists

and surgeons worked in the resuscitation ward.

Here patients received whole blood, pooled plasma,

and 5% dextrose and water. If time allowed, the

anesthetist conducted an examination of the patient

before determining his presurgical medication. The

anesthetist routinely used atropine (gr 1/100,

equivalent to 0.6 mg), often in combination with

morphine, given intravenously. The application of

anesthetic care to trauma developed greatly during

World War II, when evacuation from the front line

to definitive care took 4 to 6 hours.25

Evacuation began shortly after an aid man gave

the conscious casualty morphine and called for a

litter squad. Depending on the wound, the medic

administered plasma; dressed the wound; and filled

out an emergency medical tag indicating the man’s

name, serial number from his dog tag, and the

nature of the wound. The battalion aid station litter

squad carried the wounded man back to the aid

station, where he was examined for the first time by

a medical officer, the battalion surgeon. The surgeon could administer more plasma and morphine

and send the casualty to the collecting station for

transfer by ambulance or litter bearer to the division clearing station, located 5 to 10 miles behind

the front. Here, surgeons assigned to auxiliary

teams performed acute surgical care, and, in the

European and Mediterranean theaters, shock teams,

including an anesthetist, saw the patient for the first

time. When the patient was strong enough to be

moved again, medical personnel transported him

another 8 to 12 miles to an evacuation hospital, still

under canvas and still in the combat zone. After the

provision of definitive care, hospital authorities

either evacuated the casualty to the rear or, if he was

fully recovered, sent him forward for return to

duty.45

Shock wards of field or evacuation hospitals were

crucial to a patient’s recovery during evacuation.

Shock wards were headed by medical officers chosen from the internists or junior surgeons on the

staff, or led by anesthetists and surgeons when the

flow of casualties was heavy. Ideally, specific surgical or shock teams were assigned to the patient

and stayed with him throughout his surgery to

provide continuous care.42

The shock teams appraised the wounded man’s

therapy needs to enable him to tolerate surgery or

evacuation to a rear hospital. A patient in shock did

not remain in the same condition for any length of

time. The team assessed the man’s trends in both

pulse rate and blood pressure (their quality and

upward or downward trends were most important)

to check the adverse forces at work. His degree of

thirst and mental status, both of which medical

officers paid little attention to in World War I, were

found to be useful in evaluating the degree of shock.

It was important to prevent a regression in the

patient’s condition in preparation for surgery.42

The anesthetist continued management of the

hypovolemic patient in the operating room, administering high concentrations of oxygen to reestablish normal metabolism; anesthesia to abolish pain;

blood transfusions to restore and maintain blood

volume; dextrose and saline to rehydrate patients;

and artificial respiration, if conditions indicated.

The anesthesia providers did all they could to maintain a viable patient, while the surgeons worked as

quickly as possible in light of the patient’s needs.42

Casualties in shock or who had been in shock

were usually easy to anesthetize, probably as a

result of the resuscitation process practiced by military anesthetists. Military patients seldom experienced severe excitement—in contrast to patients in

shock in civilian practice. Military anesthetists gave

casualties in shock a light anesthesia compatible

with their surgery because such patients tolerated

deep anesthesia for brief periods only. Sometimes

anesthetists authorized to administer curare used

the agent as a muscle relaxant to facilitate intraperitoneal manipulations during periods of light anesthesia. Patients in shock, suffering thoracoabdominal wounds, or both, received nitrous oxide–ether

anesthesia by the closed endotracheal technique

and curare in various dosages and at various times

during the operation. None of those cases suffered

postoperative complications or deaths that could be

attributed to the use of curare. Anesthesia providers stressed the importance of employing the endotracheal technique when using curare. Military

anesthetists greatly expanded the role of the anesthesia provider in the care of the trauma patient

during World War II.42

Volume resuscitation was pivotal in the treatment of patients in shock during the war. Early in

the conflict, physicians relied on blood plasma because of the limited supply of whole blood, which

resulted from general unpreparedness for war, and

a myriad of theories about shock. Some experts

considered blood plasma as effective as whole blood

in the treatment of shock, easier to preserve and

transport than whole blood and without the requirement of matching and typing. Shortages of

blood for volume replacement, despite the use of
Anesthesia and Perioperative Care of the Combat Casualty

880

blood donors in the field, meant a delay in surgery

until the patient was stabilized. In February 1943,

patients received treatment for shock in clearing

stations for up to 24 hours before surgical therapy

was even attempted. Medical officers did not

give blood postoperatively to overcome anemia

and promote wound healing or, for that matter,

oxygen to improve circulation during this early

period.33,42

The readier availability of whole blood in 1944,

which followed the establishment of blood procurement centers in U.S. cities and refrigerated blood

banks in rear combat hospitals, led to a change in

the concept of stabilizing the casualty first, in favor

of rapid preparation for surgery and a reduction in

the time lag as compared with 1943. The concept of

prompt operation required an understanding of

what could be achieved by resuscitative measures

and what was impossible. Medical officers came to

realize that all that was needed was to make the

patient safe for surgery. Since a seriously wounded

man could slip back into shock once he had been

brought out of it, surgery should not be delayed

once he was resuscitated from shock. World War II

anesthesiologist Lieutenant Colonel Henry K.

Beecher stated that

all military surgeons, no matter what their original

point of view, eventually realized the importance

of operating as soon as the patient had been brought

to optimum status within a minimum period of

time.42(p21)

The recognition of the essential unity of resuscitation and operation was an important surgical advance late in the war. The lessons learned about

volume resuscitation in World War I had to be

relearned in World War II.

Military surgeons also changed their minds about

blood plasma’s usefulness in the treatment of shock.

The consideration of plasma as the ideal substitute

for whole blood in the emergency treatment of

shock and hemorrhage in war wounds was so entrenched early in the war that it handicapped the

development of more effective measures for the management of shock. As the war progressed, however,

experience proved the effects of plasma to be transient. Plasma brought men out of shock and maintained blood volume during transportation to the

hospital, where a blood transfusion could be started.

Plasma became a lifesaving stopgap measure only

until the patient could receive whole blood.42

British anesthesiologists had concluded similarly

about the transient nature of blood plasma. Of the

10% of all patients requiring resuscitation before

surgery in British forward hospitals in March 1943,

one out of five required whole blood.

If treated with plasma alone, [remarked a medical

officer of No. 1 Casualty Clearing Station in southern Tunisia,] the blood pressure [could] be brought

back but [fell] again with operation and [did] not

come back a second time. Patients treated with

plasma remain[ed] pale, the pulse [was] rapid and

the labile blood pressure [was] very sensitive to

further operative procedures.33(p36)

In general, wounded American soldiers received

one additional unit of plasma to three units of

whole blood at the hospital. About two thirds of

patients received another 500 mL of blood each,

and about one third received 1,000 mL of blood

each. Patients were considered ready for surgery

when the systolic blood pressure was 80 mm Hg

and tending upward, when the pulse volume was

good and the rate tending downward, and when

the skin was warm and the color good. Sometimes

albumin, which was expensive in terms of the

quantities of blood needed to prepare it but had

small bulk (corpsmen could line their pockets with

it), was used to elevate a low blood pressure in

situations in which space and weight were at a

premium.42

To establish effective resuscitation procedures

based on scientific evidence, the medical department set up stationary research laboratories in the

Mediterranean theater in late 1943 and early 1944

“to study by formal biochemic [sic] methods certain

aspects of shock, hemorrhage, and dehydration,”33(p348) and a mobile laboratory in September

1944, called the Board for the Study of the Severely

Wounded in the Mediterranean Theater of Operations, “to observe shock on a big scale”33(p353) and get

insights into its nature. In the opinion of the Medical Research Committee of the theater,

[i]t was essential...that the so-called impressions

derived from experience be documented by hard,

cold facts about the condition of a freshly wounded

man.... The collection of data needed to be extended to a sufficient number of casualties to make

the findings conclusive.33(p349)

The loss of lessons learned from World War I due to

the absence of convincing data and the confusion

over shock therapy early in World War II were the

catalysts for this effort at documentation by scientific evidence of effective resuscitation procedures

experienced during World War II.
A Brief History of Military Anesthesia

881

Data collected from studies of thousands of badly

wounded soldiers during the Italian campaign

proved that the liberal use of whole blood transfusion was necessary for the success of reparative

wound surgery. Extensive laboratory tests on at

least 37 of those patients confirmed the absence of

hemoconcentration in shock. The mobile research

team, headed by Colonel Beecher, studied the physiological effects of blood loss in 186 severely wounded

patients, concluding, in the broadest sense, that

“wound surgery [was] inseparable from the management of wound shock.”46(p13) Surgery became

part of the continuous process of resuscitation. The

team also determined that plasma, whole blood,

penicillin, and sulfa drugs were not harmful to the

kidneys, a question of concern in treating the severely wounded. Studies of wounded patients immediately after admission to forward hospitals

helped to formulate procedure for the clinical management of the seriously impaired.33,46

Other resuscitative measures used in World War

II included

• relief of physical and mental pain by sedation (barbiturate, usually sodium amytal)

and administration of morphine,

• management of the local wound through

control of hemorrhage and the application

of splints,

• conservation of body heat,

• emptying of the stomach before anesthesia

to avoid the risk of aspiration, and

• administration of oxygen to produce a lowered pulse rate and a better coloration of

the blood.

Medical officers administered oxygen by nasal tube

after it had been humidified by being bubbled

through a water column. Patients usually tolerated

well a gas flow of 4 to 5 L/min of 100% oxygen. A

closed system with carbon dioxide absorption, usually by the Beecher machine, provided higher concentrations of oxygen, if needed. Vasoconstrictor

and stimulating drugs were of no value in the management of battle casualties and were almost never

used.33

Auxiliary Surgical Groups

To assure quality anesthesia and surgery, specialty consultants from Auxiliary Surgical Groups,

each consisting of four surgical teams that performed frontline surgery in the absence of hospitals, visited forward units to check on patient supervision. Those consultants addressed relevant problems and recommended solutions.47

Statistics

Statistics from the Mediterranean theater reveal

a record of safety in the prevention of anesthesia

deaths. Surveys conducted in the Mediterranean

theater in September 1943 and September 1944 show

only 12 deaths attributed to anesthesia in 27,564

administrations of anesthetic agents.38(p78) Seventh

U.S. Army hospitals attributed 11 deaths in 44,630

cases wholly or in part to anesthetic administration

between 1 November 1944 and 30 April 1945.39(p550)

One World War II anesthesiologist credited this

safe record to more standardized methods and increased experience,38(p78) which made anesthesia

safer for the seriously wounded man.38 Statistics for

World War II are sadly lacking, however, regarding

numbers of physician and nurse anesthetists, anesthesia deaths in other theaters, and the frequency

and place of employment of specific agents and

techniques.

World War II Experience in Summary

World War II (1939–1945), like most wars, began

with shortages of almost everything, including anesthesia providers. Continual training in anesthesia at home and overseas helped to provide the

armed forces with skilled people, but never in the

numbers needed. Although a variety of anesthetics

were on hand during the war, ether’s availability,

ease of administration, and margin of safety made

the agent most popular. Sodium thiopental given

intravenously proved invaluable for preliminary

anesthesia or as a sole agent. Sodium thiopental’s

compactness and ease of induction made it an ideal

anesthetic for the good-risk patient under combat

conditions.

Closed-circuit anesthesia with the simple Beecher

machine gradually gained wide acceptance as a

satisfactory method at forward area hospitals, where

portable machines were needed. The apparatus

proved useful in combat for inhalational anesthesia, the administration of oxygen, and artificial respiration.

The availability of whole blood in theaters of

operation and the development of shock wards

improved treatment and resuscitation of the patient

in shock. Finally, medical departments in World

War II officially recognized the administration of
Anesthesia and Perioperative Care of the Combat Casualty

882

anesthetics as a highly skilled occupation and the

anesthetist as a specialist.

Postwar Recruitment

After demobilization, the U.S. Army had to find

ways to attract qualified physicians into military

service. The army’s acceptance of specialization,

which resulted in the establishment of residency

programs in 1947, helped. The army, like the navy,

however, still depended on civilian reserve officers

to serve as consultants to those programs. In 1948,

to obtain specialists, the army began commissioning residents in civilian hospitals for service in the

army. Most volunteers for this program had received some financial support from one of the military services during their medical school training.

With specialization so popular and widespread in

the country, the army began to develop graduate

education programs that would maintain military

medical standards while attracting and retaining

skilled physicians in the service. By 1950, those

programs were well on their way.18

The Korean War

Graduate medical education programs helped

meet the needs of mobilization for the Korean War

(1951–1953), which began with North Korea’s invasion of South Korea in summer, 1950. The armed

forces took young physicians who had recently

finished residency programs in military hospitals

and sent them to Korea. According to Howard D.

Fading, Consultant in Neurology to The U.S. Army

Surgeon General, the army’s residency program

“saved the bacon in the Korean War, and if it can

never demonstrate another value, this alone proved

its worth.”18(p12)

When the numbers of medical officers were insufficient to meet the armed forces’ needs, they

began to draft young physicians from civilian hospitals and graduate education programs. The doctor draft in January 1951 helped relieve the critical

shortage of medical officers, and courses given at

general hospitals helped relieve the shortfall of

nurse anesthetists, but specialists, including anesthesiologists, were in short supply throughout the

war.18

At first notice, the treatment of the battle casualty

in Korea seemed almost ideal. Personnel, equipment, and supplies, in most respects, were adequate.

There were ample amounts of whole blood and

prompt evacuation of the wounded from Korea.

Casualty buildup did not pose a problem. Nor were

new data gathered on the anesthetic management

of the wounded during the Korean War.48

But this picture was deceiving. Casualty care in

Korea was far from ideal. Frontline evacuations

were less effective in Korea than in World War II.

Korea’s mountainous terrain meant a long evacuation from the front to the aid station and from

the aid station to the mobile army surgical hospital (MASH). The helicopter helped, but there

were never enough. At a meeting of the Armed

Forces Medical Policy Council on 18 June 1951,

Brigadier General Crawford F. Sams, head of SCAP’s

(Supreme Commander for the Allied Powers) Public Health and Welfare Section, said he did not

doubt

the quality of the front-line hospitals and the professional care available in them. [But, he lamented,]

our death rate...is far higher than the last war

because many do not reach the hospitals.... My

impression is about 4,000 men [who have died]

should be alive.49(p189)

Senior U.S. Army medical officers linked defective evacuation directly to medical specialization

and professional development within the army to

the detriment of military training. As army medicine became more professional, more expert, and

more in line with civilian medicine, the army neglected to prepare physicians for field service. The

army plucked young physicians straight from army

hospitals and sent them to Korea without having

had field medical experience. To meet immediate

needs early in the war, medical officers in the civilian internship program also found themselves on

the Korean front with no military training, and they

suffered. Afteraction reports revealed that “some

were captured, some were killed, [and] many performed ineffectively as officers.”18(p11)

Additionally, the budget cuts of 1949 and 1950

had left the armed forces deficient in men, supplies,

and training. Financial constraints had produced a

paucity of medical personnel and hospital beds,

with which a peacetime army could deal, but which

became a problem once war began. The U.S. Army

never had as many medical units in Korea as it

needed; ambulance companies numbered about half

of what was required, and the 750-bed evacuation

hospital, which served as the backup unit to the 400-

bed evacuation hospital and field and surgical facilities, was absent from Korea. Evacuation hospitals could not absorb sudden heavy casualty loads.

Only U.S. air superiority and the presence of U.S.

Army hospitals in Japan helped prevent a backlog

of casualties awaiting evacuation from Korea. The
A Brief History of Military Anesthesia

883

MASH worked well, and the blood program and

combat psychiatry repeated the successes of World

War II. But combat medics had to learn basic military surgical procedures “like wound debridement

and delayed closure.”49(p363),50

The lessons of World War II regarding anesthesia

were also mostly forgotten. The limitation on the

amount of anesthetic equipment and supplies that

could be brought to the front made a variety of

agents and techniques unavailable. Qualified anesthesiologists were scarce in forward units, such as

surgical hospitals, where judgment and experience

were highly necessary. Little standardization of

anesthesia equipment made interchanges difficult

among U.S. models, and among U.S. machines and

those of other countries. There were national differences in terminology, electric current, and the coloring of gas cylinders. For example, a green U.S.

cylinder contained oxygen and a green British cylinder contained carbon dioxide. Such practices led

to letters of complaint to members of the U.S. Congress about the dismal anesthesia conditions in the

war zone.26

Anesthesiology, like other medical specialties,

was in a time of transition. The machines available

to the armed forces were the World War II variety:

the pig, the Foregger and McKesson machines, and

the Beecher device. Some reserve officers brought

their own anesthetic machines from civilian practice to Korea. An anesthesiologist from Massachusetts General Hospital, sent to the Far East Command to investigate anesthesia problems, brought

with him a new compact anesthesia machine as well

as methadone, a morphine substitute then undergoing clinical trials in the United States.26,49

The preferred agent and machine depended on

the anesthetist’s orientation and training. Some

received training in sodium thiopental for the seriously wounded; others in nitrous oxide with adequate amounts of oxygen. One anesthesiologist

reported using 50% to 60% nitrous oxide in oxygen

(most likely with a relaxant and a narcotic) on the

severely wounded patient, with satisfactory results.

He wanted to spare the hypovolemic patient the

consequences of a more potent depressant. Without definitive data to prove one agent or technique

better than another, Robert D. Dripps, Civilian Consultant in Anesthesia to The U.S. Army Surgeon

General, remarked, “[I]t seemed wise to permit

anesthetists to apply those methods with which

they [were] most familiar.”48(p119) Regardless of

which agent or machine was used, Dr. Dripps continued, the patient’s susceptibility had to be kept in

mind and his dosage carefully watched.48

Anesthesia providers reported using cyclopropane for the hypovolemic patient, and with good

results. They also prepared a 0.5% solution of

procaine for infiltration anesthesia and a 1% solution for nerve block. The muscle relaxant drugs,

especially tubocurarine chloride and succinylcholine, proved useful in allowing rapid intubation of

the trachea and providing muscular relaxation for

varying periods of time. Patients in shock sometimes reacted to succinylcholine with exaggerated

motor activity, resembling clonic convulsions. One

anesthesiologist suggested that this represented a

diminished amount of plasma cholinesterase. During the Korean War, anesthesiologists thought that

shock exaggerated the motor activity associated

with succinylcholine. Future anesthesia providers

would know that motor activity resembling convulsions was a normal response to succinylcholine and

not exaggerated by hypovolemia. For preoperative

medication, anesthetists in Korea used morphine or

sodium thiopental intravenously, as had been done

in World War II.48

The lessons of World War II regarding resuscitation were retained for the Korean War, except that

in Korea more information was available about the

problem of homologous serum jaundice in untreated

plasma. After World War II, plasma was subjected

to ultraviolet sterilization as part of its processing

to prevent serum hepatitis. But complete sterilization was never achieved, and hepatitis continued to

follow the use of plasma no matter how it was

treated. During the Korean War, the armed forces

had to take the calculated risk of using plasma, even

though it might cause hepatitis, because they needed

an agent for resuscitation until the casualty could

reach an installation and receive a transfusion of whole

blood. The risk was considerable. Late in 1951, the

incidence of hepatitis after plasma transfusion reached

21%, in sharp contrast to the reported World War II

incidence of 7.5%. Part of the explanation was that

much of the plasma used in Korea in the first months

of the war had not been treated at all. Moreover,

different diagnostic criteria were used in the two

wars. In World War II, the diagnosis was chiefly

clinical. In the Korean War, any elevation of the

serum bilirubin was considered an indication of

hepatitis. On 20 August 1953, Circular No. 73,

Department of the Army, directed that because of

the risk of serum hepatitis, the higher cost, and the

need to use it for the production of specific globulins, plasma would not be used “to support blood

volume” unless dextran was not available.35

The Korean War experience provided lessons for

the future regarding equipment, organization, edu-
Anesthesia and Perioperative Care of the Combat Casualty

884

cation, and training. Among the recommendations

made were the following48:

• the standardization of equipment, fittings,

and electrical current;

• the inclusion of equipment for infants and

children in anesthesia kits (one seventh of

the South Korean population were refugees at some time during the war);

• the provision of a field anesthesia record

that would fit into the emergency medical

tag jacket and accompany the casualty; and

• increases in numbers and varieties of drugs.

Also promoted were the following48:

• the employment of anesthesia consultants

in forward surgical hospitals, in order for

them to obtain first-hand knowledge of the

problems involved so as to advise and train

others more authoritatively;

• the collection of data on techniques used

for various operations, deaths related to

anesthesia, the anesthetics administered,

and the physical condition of the patients;

• the preparation of manuals and training

films for military anesthetists that would

include the basic aspects of resuscitation,

pharmacology, and physiology; and

• the study of problems associated with the

management of battle casualties and nuclear

and chemical warfare.

Many questions arose from the anesthesia experiences of World War II and the Korean War that

required investigating.

Although the importance of anesthesia and combat care were appreciated in World War I, World

War II, and the Korean War, only in 1954 did the

U.S. Army institute a 3-year residency program in

anesthesiology, following an internship. Also, after

the Korean War, the appointment of a senior consultant in anesthesia to the Office of The Surgeon

General helped initiate the correction of some of the

anesthesia problems that had been revealed during

the Korean War. In civilian medicine, university

departments of anesthesiology had begun to break

away from the surgical departmental structure and

to emerge as separate departments.47,48,51

While anesthesia came into its own in civilian

hospitals, the Selective Service Act of 1950 and the

Cold War of the 1950s and 1960s produced a large

peacetime military establishment. To support this

establishment and keep pace with the standards of

medical care provided in civilian life, the medical

department needed to expand and improve its

method of recruitment. The appointment of Dr.

Frank Berry, a colonel in World War II and a New

York surgeon, as Assistant Secretary of Defense for

Health and Medicine was an important step in that

direction. In 1954, the Berry Plan permitted physicians to postpone their military obligation under

the draft until they completed their internship and

residency programs: “This allowed for the continuous training of doctors (a pedagogical good) while

at the same time providing the military services

with completely qualified medical specialists.”18(p13)

Retention of physicians with only a 2-year military

obligation under selective service, however, remained difficult, and the balance between specialists and general medical officers suffered.18

Another way the military acquired specialists

was to make specialist training available to its medical officers. Twenty-four residency training programs in 8 army hospitals in 1959 grew to 28 programs in 17 hospitals a decade later, as the army

built up for the Vietnam War. Expanding residency

programs helped retain physicians through either

military obligation or personal decision. Specialized training also permitted the military to meet the

standards of civilian care.18

The new emphasis on specialized training benefited military anesthesia, which was fast becoming

an important part of the structure of the U.S. Army

Medical Department. The army acquired skilled

anesthetists by offering members of the U.S. Army

Nurse Corps 52 weeks of training in anesthesiology

at six U.S. Army Medical Centers and Hospitals,

namely, Brooke Army Medical Center, Walter Reed

Army Medical Center, and Letterman, Fitzsimons,

Beaumont, and Madigan Army Hospitals. Nurse

anesthetists also attended anesthesia workshops at

army hospitals. The training of U.S. Army nurse

anesthetists met the requirements for certification by

the American Association of Nurse Anesthetists.52

Besides offering internships and residencies in

anesthesia, the U.S. Army Medical Department arranged for Medical Corps officers to take long

courses in anesthesiology at civilian institutions,

such as the University of Pennsylvania, and to attend review sessions in anesthesiology at Lackland

Air Force Base, Texas. With the army’s encouragement, military anesthesiologists in increasing numbers became board certified. No longer was the medical department dependent on civilian medicine for

anesthesia consultants; it had its own professors of

anesthesiology, although it still relied on skilled

nurse anesthetists to augment hospital staffs.52
A Brief History of Military Anesthesia

885

The Vietnam War

By the mid-1960s and the Vietnam War (1965–

1972), military anesthesiologists were making the

tough decisions, like what (people, agents, and

machines) to bring to battle and what to leave home,

and what level of care to provide. Civilian anesthesiologists had faced those issues during World

War I and World War II. Incorporating lessons

learned from previous wars regarding anesthesia

care and evolving new concepts about critical care

in Vietnam, the military

• deployed anesthesiologists to forward

medical support hospitals;

• expanded the role of the anesthesiologist in

the sustainment of life before, during, and

after surgery;

• advanced the resuscitative process;

• introduced new anesthesia machines; and

• standardized anesthesia equipment.

These anesthesiologists also developed in Vietnam

many of the ideas, particularly regarding critical

care, subsequently used in civilian anesthesia in the

United States. Developments in anesthesiology

during the Vietnam War years have been well described elsewhere by Manfred (“Dutch”) Lichtmann,

an army anesthesiology professor who served in

Vietnam and later as Consultant in Anesthesiology

to The Surgeon General.47

The allocation of anesthesia providers to Vietnam followed the pattern of the deployment of

regular troops. Early in the war, anesthesia personnel were sent as advisors and then as members of

“K” teams assigned to fixed facilities and rotated to

other hospitals according to casualty needs. After the

military buildup of 1965, anesthesia personnel strength

multiplied, with nurse anesthetists forming the bulk

of the increase. Their numbers from 1968 until the

phase-down began were about 65 but reached as high

as 95 at one time. To obtain nurse anesthetists, the

army fostered a move toward nurse anesthesia education at the master’s degree level and upgraded the

requirements for attaining such a degree.47,53

Anesthesiologists, trained to board-certification

levels in military residency programs, were first

deployed to forward surgical hospitals during the

Vietnam War. Fully trained or board-certified anesthesiologists, however, were a luxury in Vietnam,

as the residency training program, although growing, was still small. Of the 35 anesthesiologists

covering 16 hospitals in 1967 through 1968, only 4

were board certified, 16 were fully trained, and 15

had learned on the job. The latter were sent directly

to Vietnam following an internship and 14 weeks’

instruction in anesthesiology. Although the army

hoped that the physician trained on the job would

work with another anesthesiologist, sometimes the

former physician was the only anesthesiologist at

the hospital. In those cases, the physician relied on

an experienced nurse anesthetist to help and guide

him. Together they formed a solid anesthesia care

team. Lichtmann recalled:

The severity of casualties, the austerity of the environment, and the continuous pressure and intensity of the care required molded physician and

nurse anesthetist into a cohesive anesthesia care

team.47(p1300)

The anesthesia care team that Lichtmann referred

to was an ideal, brought about by the exigencies of

war. The rivalry between nurse anesthetists and

physician anesthesiologists was put aside to deal

with the problems at hand. While nurse anesthetists played an important role in military medicine—the armed forces needed them—they played

a less significant role in civilian medicine, where

physician anesthesiologists reigned supreme.

This team helped care for many casualties during

the Vietnam War. The U.S. armed forces suffered

46,000 killed in Vietnam and 300,000 wounded.54(p410)

The wounds were usually multiple and devastating, the result of mine, high-velocity missile, and

booby trap injuries. Yet casualties who would not

have survived in other wars were salvaged here.

Crucial to their survival were the immediate availability of whole blood, rapid resuscitation from

shock, and helicopter transfer to hospitals. The

latter brought the patient to definitive treatment

faster than in any previous war. The time between

wounding and effective treatment averaged 10 hours

in World War I, 5 hours in World War II and Korea,

and 1 hour in Vietnam. Rapid and effective air

evacuation meant recovery for most of the wounded

who reached definitive care.54,55

Speedy helicopter evacuation from the front in

Vietnam also allowed continuous resuscitation.

Initially the corpsmen, who were trained at the

Medical Field Service School by noncommissioned

officers and sometimes physicians, restored breathing (usually through mouth-to-mouth resuscitation)

and occasionally started infusions of intravenous

fluids. Helicopter evacuation medics continued the

process. At the hospital, medical personnel started

a 14-gauge intravenous line in the basilic or the

external jugular vein and, under the supervision of
Anesthesia and Perioperative Care of the Combat Casualty

886

or managed by an anesthetist, performed airway

care, which sometimes required the use of an oropharyngeal tube, an endotracheal airway, or a

tracheostomy. The triage officer selected those casualties who responded to resuscitation for anesthesia and surgery on the basis of severity of wounds.

He informed anesthesia personnel which patient

was next and the patient’s condition. Well-functioning operating rooms had good coordination

between the triage area and anesthesia providers.47,56

Anesthesia personnel continued resuscitation in

the operating room and provided anesthesia. Those

casualties who could not be resuscitated without

surgical intervention received slight anesthesia with

airway and ventilation control and continued “infusions of blood, colloids, and electrolytes.”56(p800)

While surgical teams operated on the patient to

repair wounds, anesthesia personnel used all their

skills to help keep the patient alive. John Jenicek,

Consultant in Anesthesiology to The U.S. Army

Surgeon General during the Vietnam War, described

the expanding role of anesthetists in support of

surgical procedures during that conflict.47,56

It [became] the mission of the anesthesia team to

support the circulating volume, the oxygen demand, and the anesthetic needs of the patient as

well as to treat and correct all abnormal physiological and pharmacological responses of the casualty;

all the while providing as near optimal surgical

conditions as possible for the other equally busy

surgical teams. It is this new concept of resuscitation-anesthesia-surgery, organized and functioning as a unit [and combined with speedy evacuation], which [produced] the highest survival rate

seen in any conflict thus far.56(p800)

This new approach to field medicine—continuous

resuscitation combined with speedy evacuation—

resulted in lowered hospital mortality: 2.2% in Vietnam compared with 4.5% in World War II. Significantly more critically wounded survived to reach

base hospitals in Vietnam than in World War II.

Eighty-seven percent of those hospitalized in Vietnam returned to duty, another wartime record.55

Preoperative medication and induction techniques during the Vietnam War followed civilian

practice. With no standardized policy on premedication established, anesthesia providers based their

drug selection on their background and training.

The most commonly used premedication drugs were

the barbiturates (pentobarbital, secobarbital) and

morphine with atropine or scopolamine. The induction agent of choice was sodium thiopental used

with a relaxant.47

Problems associated with induction anesthesia

included the reduction or elimination of the patient’s

protective responses to hypovolemia caused by too

large a dose, the increased chance of tracheal aspiration of gastric contents because of soldiers eating

immediately before being wounded, and cardiac

arrest on induction of anesthesia by patients who

received succinylcholine after suffering muscle injuries or severe burns. Finally, mismanagement of

the airway or a short period of apnea during induction sometimes proved lethal. Gale Thompson, the

first consultant in anesthesiology to be sent to Vietnam, reported that 76% of patients receiving general anesthesia received tracheal intubation. There

are no statistics available for anesthesia deaths.47

Military anesthesiologists used a variety of agents

and machinery in Vietnam because the war escalated slowly, allowing the U.S. Army Medical Department to establish in the combat zone large fixed

hospitals (unlike in World War II, where mobile

hospitals were the norm) with sophisticated equipment and skilled staffs. The chief anesthetic agents

used included diethyl ether, halothane, methoxyflurane, nitrous oxide–oxygen, and spinal anesthetics. Of the 282 anesthetic administrations, mainly

on civilians, given at the 8th Field Hospital from

April 1962 to January 1963, 9% were diethyl ether,

15% halothane, and 39% spinal anesthetics, according to John Chase Daniels, the first U.S. Army

anesthesiologist in Vietnam.47

Early in the war, halothane, which had widespread use in the United States, received limited use

“because it caused hypotension and could prove

lethal in the ‘in-circuit’ vaporizers that were on

field machines,” recalled Lichtmann.47(p1302) According to Brian F. Condon, a U.S. Army anesthesiologist in Vietnam and later Consultant in Anesthesiology to The U.S. Army Surgeon General:

The “in-circuit” vaporizer or “number 8 jar” allowed the concentration of anesthetic to be varied

by the pulmonary minute volume as well as the dial

setting. This made prediction of anesthetic agent

inspired concentration difficult. Therefore a

hypovolemic, low–cardiac-output patient could

easily be overdosed and hypotension could occur

with little or no warning.57

After the U.S. Army equipped field machines

with the Fluotec Mark 1 and 2 vaporizers in 1967,

halothane replaced ether as the standard field anesthetic. As a trauma anesthetic, halothane’s advantages included nonflammability, rapid recovery after brief operations, less nausea and vomiting than

with ether, and good urinary production after fluid
A Brief History of Military Anesthesia

887

TABLE 31-1

ANESTHETIC ADMINISTRATION, U.S. ARMY 67TH EVACUATION HOSPITAL,

DECEMBER 1970 TO JULY 1971

Anesthetic December February April June July Percentage

Administration 1970 1971 1971 1971 1971 Total of Total

N2O–O2 28 5 4 6 43 4

N2O–O2-Halothane 86 71 40 34 32 263 26

N2O–O2-Methoxyflurane 51 74 102 19 11 257 26

N2O–O2-Meperidine 18 21 25 3 3 70 7

N2O–O2-Morphine 7 1 23 20 8 59 6

Axillary 10 2 6 18 2

Spinal 24 11 6 5 10 56 6

Caudal 3 1 4 —

Intravenous 6 49 37 64 40 196 19

Ketamine 27 35 52 32 146

Innovar 21 2 12 8 43

Diazepam 1 1

Infiltration 17 11 10 38 4

1,004

Operative deaths 3 2

Total number of cases 235 236 247 156 110 984

N2O: nitrous oxide; O2: oxygen

Reprinted with permission from Lichtmann MW. Vietnam. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St.

Louis, Mo: Mosby–Year Book; 1993: 1302.

resuscitation. The drug, which could be given with

oxygen alone, became the most frequently administered anesthetic from 1968 to 1971.47

Other anesthetic agents proved highly beneficial

in Vietnam. Methoxyflurane served as an analgesic

for short procedures or to augment muscle relaxation in prolonged abdominal operations. The drug

could function in “large in-circuit vaporizers” and

in “low-flow, high-oxygen systems.”47(p1302) From

1970 on, nitrous oxide–oxygen with a relaxant, a

narcotic, and, at times, a major tranquilizer added,

became a popular general anesthetic as the use of

halothane decreased. The literature of the time

reported on hepatic injury due to halothane.

Meperidine or morphine and later fentanyl became

the most frequently used narcotics.

Innovar, a combination of droperidol, a major

tranquilizer, and fentanyl, a synthetic high-potency

narcotic, sold in a fixed ratio of one to the other, was

found to be difficult to use (too much droperidol)

and to cause patients to be sleepy and even catatonic

in the recovery room. Anesthetists began using the

drugs separately, with the droperidol, the longerlasting drug, given near induction and fentanyl added

as the patient required. This combination became the

main anesthetic in the last years of the war.47,57

Ketamine proved valuable as a primary anesthetic agent for superficial wounds, “with the incorrect assumption that patients could protect their

airways under its influence.”47(p1302) Popular relaxants were succinylcholine used for induction, and

curare used for maintenance. To avoid prominent

hypotension, anesthesiologists administered curare in two or three incremental doses. Doses of

neostigmine and atropine reversed the effect of

competitive relaxants. Because field hospitals had

no Wright respirometers or blockade monitors, anesthesia providers estimated reversal by observing

the patient’s cough, hand-grip strength, and head

or arm lift.47,57

Various forms of regional anesthesia proved useful, as well. From February 1970 to May 1971,

anesthesia providers at the 91st Evacuation Hospital performed spinal anesthesia in 15% of cases.
Anesthesia and Perioperative Care of the Combat Casualty

888

TABLE 31-2

ANESTHETIC ADMINISTRATION IN EIGHT U.S. ARMY HOSPITALS IN JANUARY 1968

Anesthetic 2nd 7th 8th 12th 24th 45th 67th 85th 93rd Percentage

Administration Surg. Surg. Field Evac. Evac. Surg. Evac. Evac. Evac. Total of Total

N2O–O2-Halothane 367 27 157 414 301 165 253 259 562 2,505 82

N2O–O2-Methoxyflurane 4 23 3 3 10 10 18 19 90 3

N2O–O2-Thiopental 16 1 7 18 4 7 5 7 62 2

N2O–O2-Ether 1

O2 5 5

Regional 1 1 30 20 15 1 10 41 15 134 4

Spinal 11 10 30 74 67 14 27 19 26 278 9

3,069

Infiltration 138 8 85 88 77 11 66 91 66

Total number of cases 539 90 431 629 501 164 371 431 636

Personnel

3115 B 1 1 1

3115 C 1 2 1

OJT 1 1 1 1 1 1

3445 2 3 3 6 6 3 4 2 5

N2O: nitrous oxide; O2: oxygen; 3115 B: board-certified anesthesiologist; 3115 C: fully trained anesthesiologist; OJT: on the job (ie,

physician partially trained in anesthesia); 3445: certified nurse anesthetist

Reprinted with permission from Lichtmann MW. Vietnam. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St.

Louis, Mo: Mosby–Year Book; 1993: 1303.

was used in 25 percent of cases primarily because that

was the only anesthetic they had available.47(p1302)

In late 1971 and early 1972, in the 95th Evacuation

Hospital in Da Nang, regional anesthesia was used

in 23% of total cases done. Axillary and interscalene

arm blocks as well as spinal and epidural blocks

were popular. A regional anesthetic for an arm

debridement in a stable patient would allow the

procedure to be done in the holding area with

minimal surgical equipment. This practice kept the

patient from going to the operating room and therefore saved sterile equipment, drapes, and the time

of skilled personnel for more serious cases. Two to

four regional procedures per day were common at

the 95th Evacuation Hospital.57

Recovery rooms in Vietnam resembled intensive

care units in major civilian medical centers. Patients who could not be safely extubated immediately after surgery required “ventilatory, nutritional,

and hemodynamic care in addition to wound

care,”47(p1302) recalled Lichtmann. Recovery room

Epidural anesthesia evinced benefits in vascular

repairs and grafts. When the casualty load was

heavy, anesthesia personnel reinjected epidural

catheters between cases in the operating room.

Upper-extremity nerve blocks and Bier blocks (regional intravenous anesthesia) also proved valuable. The absence of double tourniquets sometimes

caused local anesthetics to leak. Regional, especially spinal, anesthesia was more popular with

anesthesia providers in the Vietnam War than in

World War II. Spinal anesthesia’s simplicity made

it perfect for combat. The method had become more

popular in the civilian sector by this time as well.47

In his essay on Vietnam titled “Military and

Battlefield Anesthesia,” Lichtmann constructed five

tables (Tables 31-1 through 31-5) that

give some temporal and geographic impressions of

the anesthetics used. These reports are incomplete

but do show trends over several years, as well as the

impact of logistics, as in the case of the 67th Evacuation Hospital ([Table 31-1]), where methoxyflurane
A Brief History of Military Anesthesia

889

TABLE 31-3

ANESTHETIC ADMINISTRATION IN EIGHT U.S. ARMY HOSPITALS IN APRIL 1968

Anesthetic 2nd 12th 17th 18th 27th 36th 45th 67th 71st 85th 93rd Percentage

Administration Surg. Evac. Field Surg. Surg. Evac. Surg. Evac. Evac. Evac. Evac. Total of Total

N2O–O2-Halothane 257 409 68 154 180 111 224 294 214 603 2,771 79

N2O–O2-Methoxyflurane 7 3 3 204 1 31 3 1 13 9 4 286 8

N2O–O2-Thiopental 16 11 16 7 2 1 3 6 78 2

O2-Thiopental 1 1

Thiopental 1 1

Neurolept analgesia 1 1

Meperidine-N2O–O2 1 1

Relaxants

Curare 22 22

Succinylcholine drip 10 10

Regional

Block 4 4 3 5 6 2 1 14 29 33 107 3

Spinal 9 27 11 29 6 44 2 23 50 39 2 251 7

Epidural 2 2

3,499

Infiltration 191 46 30 198 135 63 64 237 121 35

Total number of cases 483 621 151 434 278 358 185 766 608 485 684

Personnel

3115 B 1 1

3115 C 1 1 1 1 1

OJT 1 1 1 1 1 1

3445 2 6 2 3 3 4 4 4 4 2 5

N2O: nitrous oxide; O2: oxygen; 3115 B: board-certified anesthesiologist; 3115 C: fully trained anesthesiologist; OJT: on the job (ie,

physician partially trained in anesthesia); 3445: certified nurse anesthetist

Reprinted with permission from Lichtmann MW. Vietnam. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St.

Louis, Mo: Mosby–Year Book; 1993: 1303.

staff, he stated, provided continuous nursing care,

using electrocardioscopes, defibrillators, ventilators, and other respiratory techniques, often with

the anesthesiologist in attendance.

Because there was no military occupation specialty for respiratory therapists, a system developed whereby personnel at Walter Reed Army

Medical Center identified those skilled people as

they came into service and coordinated their assignments, so that respiratory therapists were distributed throughout the hospitals in Vietnam. The

military had plenty of opportunities to practice

critical care medicine in Vietnam.47 Declared

Lichtmann: “The recovery rooms of those large

field hospitals did not differ greatly from the busy

intensive care unit of a large urban hospital....”47(p1302)

Early in the war, anesthesia equipment was

adequate but antiquated. Anesthesia providers

initially deployed brought with them the World

War II–era 0400 and 0430 Heidbrink machines (the

pig). These machines had 400-mL metal carbon

dioxide absorbers but only a closed-circle vaporizer, which, as was stated above, was not readily

adaptable for use with the newer potent inhalational agents such as halothane. In 1967, the army

adopted the Ohio Model 785 Field Anesthesia

Machine, which had undergone several design

changes since production began in 1958, and orThe
Anesthesia and Perioperative Care of the Combat Casualty

890

1970 1971

Percentage

Anesthetic Feb Mar May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar May Total of Total

TABLE 31-4

ANESTHETIC ADMINISTRATION AT THE U.S. ARMY 91ST EVACUATION HOSPITAL,

FEBRUARY 1970 TO MAY 1971

Halothane 240 248 311 239 247 235 177 162 163 189 156 165 117 65 2,714 52

Methoxyflurane 44 40 4 23 9 2 3 4 3 30 12 174 3

N2O–O2 18 13 26 10 28 62 110 91 68 72 107 147 118 104 974 19

Blocks 22 36 19 16 8 7 6 10 20 21 16 19 20 31 251 5

Spinals 93 105 65 44 37 60 68 48 62 58 49 39 47 30 805 15

Infiltration 22 15 17 7 7 6 12 10 12 15 2 8 6 11 150 3

Other 2 2 11 1 1 4 2 1 37 28 41 130 2

Ketamine 29 14 43

5,198

Endotracheal 260 221 305 * 251 284 277 230 228 256 244 303 232 167 3,258 63

Total cases 439 459 444 343 337 373 483 313 329 403 404 428 * 291 5,046

*Information missing

N2O: nitrous oxide; O2: oxygen

Reprinted with permission from Lichtmann MW. Vietnam. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St.

Louis, Mo: Mosby–Year Book; 1993: 1304.

TABLE 31-5

ACTIVITIES REPORT FOR THE U.S. ARMY 3RD FIELD HOSPITAL, 1967 THROUGH 1968

Census Year 1967 Census Year 1968 Increase (%)

Total hospital admissions 6,747 11,382 69

Surgical procedures 2,857 6,406 124

Major 1,882 3,296 75

Minor 975 3,110 219

Deaths in hospital 148 150 1

1968 mortality rate for admissions: 1.3%

1968 mortality rate for surgical procedures: 2.3%

Adapted with permission from Lichtmann MW. Vietnam. In: Grande CM, ed. Textbook of Trauma Anesthesia and Critical Care. St. Louis,

Mo: Mosby–Year Book; 1993: 1305. Numbers amended by the original author for this publication, 1995.

cylinders of nitrous oxide–oxygen; had pressure

regulators for those gases, a large in-circuit vaporizer, a heater rod

to stabilize vaporization temperatures in all

weather, [and was] capable of delivering anesthetic

mixtures over a temperature range of 4°C to 38°C....

The era of administering ether with wet-drapes

over the “ether screen” had ended.26(pp66–67)

dered a number of these machines for issue to all

medical units (Figures 31-18 through 31-21). The

new anesthesia device weighed less than 95 lb;

could be carried by one individual from surgery to

vehicle; and could be air-dropped in one package,

except for its four gas cylinders or pressure

tanks.26,47,57 The machine had a two-canister carbon

dioxide absorber; was capable of accommodating
A Brief History of Military Anesthesia

891

Fig. 31-18. Military Field Anesthesia Machine Model 785.

The ether/chloroform in-circuit vaporizer is seen at bottom left. Flowmeters, seen left to right, are for nitrous

oxide (blue), cyclopropane (orange), and oxygen (white,

the international color for oxygen). A pressure gauge,

calibrated in centimeters of water, monitors the pressure

in the breathing circuit. Immediately below the pressure

gauge is a round button, the oxygen flush valve. Two

one-way valves for the breathing circuit can be seen at the

bottom right. The white plug with a small chain attached,

seen in the center of the photograph, can be removed and

replaced by the hand-operated concertina bellows (also

see Figs. 31-19 and 31-21). Photograph: Courtesy of William Clayton Petty, MD, Captain, Medical Corps, US

Navy, Bethesda, Md.

Fig. 31-19. Military Field Anesthesia Machine Model 785,

with breathing hoses and rebreathing bag attached. Carbon dioxide–absorbent granules have been placed in the

canisters. The hand-operated concertina bellows is in

place. Photograph: Courtesy of William Clayton Petty,

MD, Captain, Medical Corps, US Navy, Bethesda, Md.

Fig. 31-20. A small, 110-volt cylindrical heater can be

installed in the vaporizer to heat ether in cold climates

and to stabilize its temperature during induction of anesthesia. A rapid ether induction can cause the outside

walls of the vaporizer to coat with ice. The heater will

maintain ether at a stable temperature, eliminating the

marked reduction in vaporization of ether during induction. Photograph: Courtesy of William Clayton Petty,

MD, Captain, Medical Corps, US Navy, Bethesda, Md.
Anesthesia and Perioperative Care of the Combat Casualty

892

Fig. 31-21. The 1968 Ohio Model 785 Field Anesthesia

Machine. Photograph: Reprinted with permission from

Model 785 anesthesia apparatus, nitrous oxide, oxygen,

ether, and cyclopropane, portable, 4-cylinder capacity.

Instruction and Service Manual. Madison, Wis: Ohio Chemical and Surgical Equipment Company; Oct 1968: 11.

well-equipped hospitals with highly trained staff;

and (2) the air superiority enjoyed by the United

States facilitated a rapid and effective evacuation

system to those hospitals for definitive treatment.

As a result, medical personnel were able to salvage

most of the wounded who had not been killed

outright on the battlefield.

The Vietnam War, more than any previous conflict, gave a new face and a new character to anesthesia providers. They played a pivotal role in

preserving life before, during, and after surgery,

redefining the meaning of intensive care. AMEDD’s

establishment of fixed, well-equipped hospitals,

specially staffed with highly trained people, provided trauma treatment to rival that of any civilian

trauma center in the world.

The Post–Vietnam War Era

The role of the anesthesiologist continued to expand in the post–Vietnam War era in the realm of

resuscitation and critical care medicine. Advancements in anesthesiology as practiced in conflicts

since the Vietnam War are well described elsewhere.58–60 The anesthesiologist diagnosed and alleviated pain by simple and complex techniques,

such as nerve block and intravenous anesthesia. In

the operating room, the anesthesiologist used modern, sophisticated equipment to administer anesthesia and monitor blood pressure, central venous

pressure, left atrial pressure, and so forth to make

surgery safer for the patient at risk. In the recovery

room, recalled Jenicek,

a skilled staff, often trained and instructed by the

anesthesiologist, provid[ed] immediate and continuous nursing care to protect the patient as far as

possible from drug-induced respiratory depression, hyper or hypotension and a myriad of

anesthetically or surgically induced occurrences

that [might] beset the organ systems at [that]

time.61(p387)

They used ventilators, antiarrhythmic drugs, cardiac monitors, or cardiopulmonary resuscitation,

often with the anesthesiologist in attendance.61

The recognition by anesthesiologists, later joined

by cardiologists and other specialists, of the possibility of saving patients by aggressive treatment in

the early stages of a debilitating illness or acute trauma

led to the discipline of critical care medicine, the

successor to intensive care medicine. Enthusiasts of

critical care designed curricula to enhance the skills

of those wishing to work in this special field.61

Vietnam War was the first conflict in which anesthesia providers used equipment standardized to

written specifications. The implements included

endotracheal tubes, laryngoscopes, adapters,

venotubes, carbon dioxide absorbents, vasopressors,

and new relaxants. The capstone to the modernization effort was the regulation of a new field anesthesia

chest. The chest weighed 110 lb when fully loaded

with over 100 items and a 3-day supply of drugs, and

could be air-dropped. Standardization provided the

army with high-quality supplies and drugs in a medical specialty “where,” according to John A. Jenicek,

former Consultant in Anesthesiology to The U.S.

Army Surgeon General, “the margin for error [did]

not tolerate a substandard approach.”56(p801)

Unlike that in any previous war, casualty care

in the Vietnam War during the late 1960s and

early 1970s was equal to, and in some respects

better than, the treatment provided in the most

sophisticated medical centers in the United States.

There were two main reasons: (1) the gradual escalation of the war enabled the U.S. Army Medical

Department (AMEDD; the acronym became established during the early 1970s) to establish fixed,
A Brief History of Military Anesthesia

893

The expanded knowledge and role of the anesthesiologist has led to more research in the field of anesthesiology and critical care, and increased and enlarged journals of anesthesiology and publications on

the subject in major scientific periodicals. To John

Jenicek, “Anesthesiology is art and science coexisting

in the world of modern medicine, in a discipline that

is demanding, exciting, and rewarding.”61(pp388–389)

Because armed combat equates with trauma,

Brian Condon, former Consultant in Anesthesiology to The U.S. Army Surgeon General, believes it

is time for a natural alliance between military anesthesia and trauma anesthesia in the civilian sphere.57

The military might help forge that alliance, especially since trauma anesthesia is receiving little

national attention at present.62

The military has shared man’s eternal quest to

alleviate pain and make possible the humane treatment of survivors. Military and civilian anesthesia

providers have learned from each other strategies

to promote the merciful treatment of the seriously

impaired patient. The military has developed its own

cadre of specialists, capable of independently solving

complex medical problems. The military’s vast and

valuable experience in caring for combat casualties

has advanced the field of critical care medicine and

has led to a natural alliance of military and civilian

anesthesiology in the treatment of trauma.

SUMMARY

Acknowledgments

The author wishes to thank Dale Smith, Ph.D., Associate Professor of Medical History, and Colonel

Robert J. T. Joy, M.D, Medical Corps, U.S. Army, (ret), Professor and Chairman, Section of Medical

History, Uniformed Services University of the Health Sciences, for their helpful suggestions and

review during the preparation of this chapter; and Captain William Clayton Petty, M.D., Medical

Corps, U.S. Navy, Professor and Vice Chairman, Department of Anesthesiology, Uniformed Services

University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, for his

advice and for providing the illustrations.

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