Evidence Report/Technology Assessment

Number 43

Making Health Care Safer: A Critical

Analysis of Patient Safety Practices

Prepared for:

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

2101 East Jefferson Street

Rockville, MD 20852

www.ahrq.gov

Contract No. 290-97-0013

Prepared by:

University of California at San Francisco (UCSF)–Stanford University

Evidence-based Practice Center

Editorial Board

Kaveh G. Shojania, M.D. (UCSF)

Bradford W. Duncan, M.D. (Stanford)

Kathryn M. McDonald, M.M. (Stanford)

Robert M. Wachter, M.D. (UCSF)

Managing Editor

Amy J. Markowitz, JD

Robert M. Wachter, MD

Project Director

Kathryn M. McDonald, MM

UCSF–Stanford EPC Coordinator

AHRQ Publication 01-E058

July 20, 2001 (Revised printing, indexed)
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Preface

The Agency for Healthcare Research and Quality (AHRQ), formerly the Agency for

Health Care Policy and Research (AHCPR), through its Evidence-based Practice Centers

(EPCs), sponsors the development of evidence reports and technology assessments to assist

public- and private-sector organizations in their efforts to improve the quality of health care

in the United States. The reports and assessments provide organizations with comprehensive,

science-based information on common, costly medical conditions and new health care

technologies. The EPCs systematically review the relevant scientific literature on topics

assigned to them by AHRQ and conduct additional analyses when appropriate prior to

developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and

health technology assessments, AHRQ encourages the EPCs to form partnerships and enter

into collaborations with other medical and research organizations. The EPCs work with these

partner organizations to ensure that the evidence reports and technology assessments they

produce will become building blocks for health care quality improvement projects throughout

the Nation. The reports undergo peer review prior to their release.

AHRQ expects that the EPC evidence reports and technology assessments will inform

individual health plans, providers, and purchasers as well as the health care system as a whole

by providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director,

Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality,

6010 Executive Blvd., Suite 300, Rockville, MD 20852.

John M. Eisenberg, M.D. Douglas B. Kamerow, M.D.

Director Director, Center for Practice and

Agency for Healthcare Technology Assessment

Research and Quality Agency for Healthcare

 Research and Quality

The authors of this report are responsible for its content. Statements in the report should not be

construed as endorsement by the Agency for Healthcare Research and Quality or the U.S.

Department of Health and Human Services of a particular drug, device, test, treatment, or other

clinical service.
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Structured Abstract

Objectives: Patient safety has received increased attention in recent years, but mostly with a

focus on the epidemiology of errors and adverse events, rather than on practices that reduce such

events. This project aimed to collect and critically review the existing evidence on practices

relevant to improving patient safety.

Search Strategy and Selection Criteria: Patient safety practices were defined as those that

reduce the risk of adverse events related to exposure to medical care across a range of diagnoses

or conditions. Potential patient safety practices were identified based on preliminary surveys of

the literature and expert consultation. This process resulted in the identification of 79 practices

for review. The practices focused primarily on hospitalized patients, but some involved nursing

home or ambulatory patients. Protocols specified the inclusion criteria for studies and the

structure for evaluation of the evidence regarding each practice. Pertinent studies were identified

using various bibliographic databases (e.g., MEDLINE, PsycINFO, ABI/INFORM, INSPEC),

targeted searches of the Internet, and communication with relevant experts.

Data Collection and Analysis: Included literature consisted of controlled observational

studies, clinical trials and systematic reviews found in the peer-reviewed medical literature,

relevant non-health care literature and “gray literature.” For most practices, the project team

required that the primary outcome consist of a clinical endpoint (i.e., some measure of morbidity

or mortality) or a surrogate outcome with a clear connection to patient morbidity or mortality.

This criterion was relaxed for some practices drawn from the non-health care literature. The

evidence supporting each practice was summarized using a prospectively determined format.

The project team then used a predefined consensus technique to rank the practices according to

the strength of evidence presented in practice summaries. A separate ranking was developed for

research priorities.

Main Results: Practices with the strongest supporting evidence are generally clinical

interventions that decrease the risks associated with hospitalization, critical care, or surgery.

Many patient safety practices drawn primarily from nonmedical fields (e.g., use of simulators,

bar coding, computerized physician order entry, crew resource management) deserve additional

research to elucidate their value in the health care environment. The following 11 practices were

rated most highly in terms of strength of the evidence supporting more widespread

implementation.

• Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk;

• Use of perioperative beta-blockers in appropriate patients to prevent perioperative

morbidity and mortality;

• Use of maximum sterile barriers while placing central intravenous catheters to prevent

infections;
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• Appropriate use of antibiotic prophylaxis in surgical patients to prevent postoperative

infections;

• Asking that patients recall and restate what they have been told during the informed

consent process;

• Continuous aspiration of subglottic secretions (CASS) to prevent ventilator-associated

pneumonia;

• Use of pressure relieving bedding materials to prevent pressure ulcers;

• Use of real-time ultrasound guidance during central line insertion to prevent

complications;

• Patient self-management for warfarin (CoumadinTM) to achieve appropriate outpatient

anticoagulation and prevent complications;

• Appropriate provision of nutrition, with a particular emphasis on early enteral nutrition in

critically ill and surgical patients; and

• Use of antibiotic-impregnated central venous catheters to prevent catheter-related

infections.

Conclusions: An evidence-based approach can help identify practices that are likely to

improve patient safety. Such practices target a diverse array of safety problems. Further research

 is needed to fill the substantial gaps in the evidentiary base, particularly with regard to the

generalizability of patient safety practices heretofore tested only in limited settings and to

promising practices drawn from industries outside of health care. 

This document is in the public domain and may be used and reprinted without permission

except those copyrighted materials noted for which further reproduction is prohibited without the

specific permission of copyright holders.

Suggested Citation:

Shojania KG, Duncan BW, McDonald KM, et al., eds. Making Health Care Safer: A

Critical Analysis of Patient Safety Practices. Evidence Report/Technology Assessment No. 43

(Prepared by the University of California at San Francisco–Stanford Evidence-based Practice

Center under Contract No. 290-97-0013), AHRQ Publication No. 01-E058, Rockville, MD:

Agency for Healthcare Research and Quality. July 2001. 
vii

CONTENTS

Summary.........................................................................................................................1

Evidence Report.............................................................................................................9

PART I. OVERVIEW ..........................................................................................................11

Chapter 1. An Introduction to the Report..............................................................................13

1.1. General Overview .......................................................................................................13

1.2. How to Use this Report ...............................................................................................18

1.3. Acknowledgments.......................................................................................................20

Chapter 2. Drawing on Safety Practices from Outside Health Care......................................25

Chapter 3. Evidence-based Review Methodology ................................................................29

PART II. REPORTING AND RESPONDING TO PATIENT SAFETY PROBLEMS ...........................39

Chapter 4. Incident Reporting ...............................................................................................41

Chapter 5. Root Cause Analysis............................................................................................51

PART III. PATIENT SAFETY PRACTICES & TARGETS ...........................................................57

Section A. Adverse Drug Events (ADEs).................................................................................58

Chapter 6. Computerized Physician Order Entry (CPOE) with Clinical Decision Support

Systems (CDSSs)....................................................................................................................59

Chapter 7. The Clinical Pharmacist’s Role in Preventing Adverse Drug Events..................71

Chapter 8. Computer Adverse Drug Event (ADE) Detection and Alerts..............................79

Chapter 9. Protocols for High-Risk Drugs: Reducing Adverse Drug Events Related to

Anticoagulants........................................................................................................................87

Chapter 10. Unit-Dose Drug Distribution Systems .............................................................101

Chapter 11. Automated Medication Dispensing Devices....................................................111

Section B. Infection Control ...................................................................................................118

Chapter 12. Practices to Improve Handwashing Compliance .............................................119

Chapter 13. Impact of Barrier Precautions in Reducing the Transmission of Serious

Nosocomial Infections..........................................................................................................127

Chapter 14. Impact of Changes in Antibiotic Use Practices on Nosocomial Infections and

Antimicrobial Resistance – Clostridium Difficile and Vancomycin-resistant Enterococcus

(VRE)....................................................................................................................................141

Chapter 15. Prevention of Nosocomial Urinary Tract Infections........................................149

Subchapter 15.1. Use of Silver Alloy Urinary Catheters .................................................149

Subchapter 15.2. Use of Suprapubic Catheters................................................................155

Chapter 16. Prevention of Intravascular Catheter-Associated Infections............................163

Subchapter 16.1. Use of Maximum Barrier Precautions During Central Venous Catheter

Insertion.............................................................................................................................165

Subchapter 16.2. Use of Central Venous Catheters Coated with Antibacterial or Antiseptic

Agents ...............................................................................................................................169

Subchapter 16.3. Use of Chlorhexidine Gluconate at the Central Venous Catheter

Insertion Site .....................................................................................................................175

Subchapter 16.4. Other Practices .....................................................................................178
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Chapter 17. Prevention of Ventilator-Associated Pneumonia.............................................185

Subchapter 17.1. Patient Positioning: Semi-recumbent Positioning and Continuous

Oscillation .........................................................................................................................185

Subchapter 17.2. Continuous Aspiration of Subglottic Secretions ..................................190

Subchapter 17.3. Selective Digestive Tract Decontamination.........................................193

Subchapter 17.4. Sucralfate and Prevention of VAP .......................................................198

Section C. Surgery, Anesthesia, and Perioperative Medicine ................................................204

Chapter 18. Localizing Care to High-Volume Centers .......................................................205

Chapter 19. Learning Curves for New Procedures – the Case of Laparoscopic

Cholecystectomy ..................................................................................................................213

Chapter 20. Prevention of Surgical Site Infections ..............................................................221

Subchapter 20.1. Prophylactic Antibiotics........................................................................221

Subchapter 20.2. Perioperative Normothermia................................................................231

Subchapter 20.3. Supplemental Perioperative Oxygen.....................................................234

Subchapter 20.4. Perioperative Glucose Control ..............................................................237

Chapter 21. Ultrasound Guidance of Central Vein Catheterization ....................................245

Chapter 22. The Retained Surgical Sponge.........................................................................255

Chapter 23. Pre-Anesthesia Checklists To Improve Patient Safety ....................................259

Chapter 24. The Impact Of Intraoperative Monitoring On Patient Safety ..........................265

Chapter 25. Beta-blockers and Reduction of Perioperative Cardiac Events .......................271

Section D. Safety Practices for Hospitalized or Institutionalized Elders................................280

Chapter 26. Prevention of Falls in Hospitalized and Institutionalized Older People........281

Subchapter 26.1. Identification Bracelets for High-Risk Patients ...................................284

Subchapter 26.2. Interventions that Decrease the Use of Physical Restraints .................287

Subchapter 26.3. Bed Alarms...........................................................................................291

Subchapter 26.4. Special Hospital Flooring Materials to Reduce Injuries from Patient Falls

...........................................................................................................................................293

Subchapter 26.5. Hip Protectors to Prevent Hip Fracture ................................................295

Chapter 27. Prevention of Pressure Ulcers in Older Patients ..............................................301

Chapter 28. Prevention of Delirium in Older Hospitalized Patients ...................................307

Chapter 29. Multidisciplinary Geriatric Consultation Services...........................................313

Chapter 30. Geriatric Evaluation and Management Units for Hospitalized Patients ...........323

Section E. General Clinical Topics.........................................................................................331

Chapter 31. Prevention of Venous Thromboembolism .......................................................333

Chapter 32. Prevention of Contrast-Induced Nephropathy .................................................349

Chapter 33. Nutritional Support ..........................................................................................359

Chapter 34. Prevention of Clinically Significant Gastrointestinal Bleeding in Intensive Care

Unit Patients .........................................................................................................................368

Chapter 35. Reducing Errors in the Interpretation of Plain Radiographs and Computed

Tomography Scans ...............................................................................................................376

Chapter 36. Pneumococcal Vaccination Prior to Hospital Discharge .................................385

36.1. Vaccine Effectiveness .............................................................................................386

36.2. Vaccine Delivery Methods......................................................................................388
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Chapter 37. Pain Management.............................................................................................396

Subchapter 37.1. Use of Analgesics in the Acute Abdomen ...........................................396

Subchapter 37.2. Acute Pain Services..............................................................................400

Subchapter 37.3. Prophylactic Antiemetics During Patient-controlled Analgesia Therapy

...........................................................................................................................................404

Subchapter 37.4. Non-pharmacologic Interventions for Postoperative Plan ...................406

Section F. Organization, Structure, and Culture ....................................................................411

Chapter 38. “Closed” Intensive Care Units and Other Models of Care for Critically Ill

Patients..................................................................................................................................413

Chapter 39. Nurse Staffing, Models of Care Delivery, and Interventions ..........................423

Chapter 40. Promoting a Culture of Safety ..........................................................................447

Section G. Systems Issues and Human Factors ......................................................................458

Chapter 41. Human Factors and Medical Devices ..............................................................459

Subchapter 41.1. The Use of Human Factors in Reducing Device-related Medical Errors

...........................................................................................................................................459

Subchapter 41.2. Refining the Performance of Medical Device Alarms .........................462

Subchapter 41.3. Equipment Checklists in Anesthesia....................................................466

Chapter 42. Information Transfer.........................................................................................471

Subchapter 42.1. Information Transfer Between Inpatient and Outpatient Pharmacies..471

Subchapter 42.2. Sign-Out Systems for Cross-Coverage ................................................476

Subchapter 42.3. Discharge Summaries and Follow-up ..................................................479

Subchapter 42.4. Notifying Patients of Abnormal Results ..............................................482

Chapter 43. Prevention of Misidentifications......................................................................487

Subchapter 43.1. Bar Coding ...........................................................................................487

Subchapter 43.2. Strategies to Avoid Wrong-Site Surgery..............................................494

Chapter 44. Crew Resource Management and its Applications in Medicine......................501

Chapter 45. Simulator-Based Training and Patient Safety..................................................511

Chapter 46. Fatigue, Sleepiness, and Medical Errors..........................................................519

Chapter 47. Safety During Transport of Critically Ill Patients............................................534

Subchapter 47.1. Interhospital Transport ..........................................................................536

Subchapter 47.2. Intrahospital Transport .........................................................................538

Section H. Role of the Patient.................................................................................................544

Chapter 48. Procedures For Obtaining Informed Consent ..................................................546

Chapter 49. Advance Planning For End-of-Life Care.........................................................556

Chapter 50. Other Practices Related to Patient Participation ..............................................569

PART IV. PROMOTING AND IMPLEMENTING SAFETY PRACTICES .......................................573

Chapter 51. Practice Guidelines ..........................................................................................575

Chapter 52. Critical Pathways .............................................................................................581

Chapter 53. Clinical Decision Support Systems..................................................................589

Chapter 54. Educational Techniques Used in Changing Provider Behavior.......................595

Chapter 55. Legislation, Accreditation, and Market-Driven and Other Approaches to

Improving Patient Safety......................................................................................................601
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PART V. ANALYZING THE PRACTICES .............................................................................611

Chapter 56. Methodology for Summarizing the Evidence for the Practices .......................613

Chapter 57. Practices Rated by Strength of Evidence .........................................................619

Chapter 58. Practices Rated by Research Priority...............................................................627

Chapter 59. Listing of All Practices, Categorical Ratings, and Comments........................633

Appendix: List of Contributors .................................................................................649

Index............................................................................................................................655
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Summary

Overview

Patient safety has become a major concern of the general public and of policymakers at

the State and Federal levels. This interest has been fueled, in part, by news coverage of

individuals who were the victims of serious medical errors and by the publication in 1999 of the

Institute of Medicine’s (IOM’s) report To Err is Human: Building a Safer Health System. In its

report, IOM highlighted the risks of medical care in the United States and shocked the

sensibilities of many Americans, in large part through its estimates of the magnitude of medicalerrors-related deaths (44,000 to 98,000 deaths per year) and other serious adverse events. The

report prompted a number of legislative and regulatory initiatives designed to document errors

and begin the search for solutions. But Americans, who now wondered whether their next

doctor’s or hospital visit might harm rather than help them, began to demand concerted action.

Three months after publication of the IOM report, an interagency Federal government

group, the Quality Interagency Coordination Task Force (QuIC), released its response, Doing

What Counts for Patient Safety: Federal Actions to Reduce Medical Errors and Their Impact.

That report, prepared at the President’s request, both inventoried on-going Federal actions to

reduce medical errors and listed more than 100 action items to be undertaken by Federal

agencies.

An action promised by the Agency for Healthcare Research and Quality (AHRQ), the

Federal agency leading efforts to research and promote patient safety, was “the development and

dissemination of evidence-based, best safety practices to provider organizations.” To initiate the

work to be done in fulfilling this promise, AHRQ commissioned the University of California at

San Francisco (UCSF) – Stanford University Evidence-based Practice Center (EPC) in January

2001 to review the scientific literature regarding safety improvement. To accomplish this, the

EPC established an Editorial Board that oversaw development of this report by teams of content

experts who served as authors.

Defining Patient Safety Practices

Working closely with AHRQ and the National Forum for Quality Measurement and

Reporting (the National Quality Forum, or NQF)—a public–private partnership formed in 1999

to promote a national health care quality agenda the EPC began its work by defining a patient

safety practice as a type of process or structure whose application reduces the probability of

adverse events resulting from exposure to the health care system across a range of diseases and

procedures.

This definition is consistent with the dominant conceptual framework in patient safety,

which holds that systemic change will be far more productive in reducing medical errors than

will targeting and punishing individual providers. The definition’s focus on actions that cut

across diseases and procedures also allowed the research team to distinguish patient safety

activities from the more targeted quality improvement practices (e.g., practices designed to

increase the use of beta-blockers in patients who are admitted to the hospital after having a

myocardial infarction). The editors recognize, however, that this distinction is imprecise.
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This evidence-based review also focuses on hospital care as a starting point because the

risks associated with hospitalization are significant, the strategies for improvement are better

documented there than in other health care settings, and the importance of patient trust is

paramount. The report, however, also considers evidence regarding other sites of care, such as

nursing homes, ambulatory care, and patient self-management.

The results of this EPC study will be used by the NQF to identify a set of proven patient

safety practices that should be used by hospitals. Identification of these practices by NQF will

allow patients throughout the nation to evaluate the actions their hospitals and/or health care

facilities have taken to improve safety. 

Reporting The Evidence

As is typical for evidence-based reviews, the goal was to provide a critical appraisal of

the evidence on the topic. This information would then be available to others to ensure that no

practice unsupported by evidence would be endorsed and that no practice substantiated by a high

level of proof would lack endorsement. Readers familiar with the state of the evidence regarding

quality improvement in areas of health care where this has been a research priority (e.g.,

cardiovascular care) may be surprised and even disappointed, by the paucity of high quality

evidence in other areas of health care for many patient safety practices. One reason for this is

the relative youth of the field. Just as there had been little public recognition of the risks of

health care prior to the first IOM report, there has been relatively little attention paid to such

risks – and strategies to mitigate them – among health professionals and researchers.

Moreover, there are a number of methodologic reasons why research in patient safety is

particularly challenging. Many practices (e.g., the presence of computerized physician order

entry systems, modifying nurse staffing levels) cannot be the subject of double-blind studies

because their use is evident to the participants. Second, capturing all relevant outcomes,

including “near misses” (such as a nurse catching an excessive dosage of a drug just before it is

administered to a patient) and actual harm, is often very difficult. Third, many effective practices

are multidimensional, and sorting out precisely which part of the intervention works is often

quite challenging. Fourth, many of the patient safety problems that generate the most concern

(wrong-site surgery, for example) are uncommon enough that demonstrating the success of a

“safety practice” in a statistically meaningful manner with respect to outcomes is all but

impossible.

Finally, establishing firm epidemiologic links between presumed (and accepted) causes

and adverse events is critical, and frequently difficult. For instance, in studying an intuitively

plausible “risk factor” for errors, such as “fatigue,” analyses of errors commonly reveal the

presence of fatigued providers (because many health care providers work long hours and/or late

at night). The question is whether or not fatigue is over-represented among situations that lead

to errors. The point is not that the problem of long work-hours should be ignored, but rather that

strong epidemiologic methods need to be applied before concluding that an intuitive cause of

errors is, in fact, causal.

Researchers now believe that most medical errors cannot be prevented by perfecting the

technical work of individual doctors, nurses, or pharmacists. Improving patient safety often

involves the coordinated efforts of multiple members of the health care team, who may adopt

strategies from outside health care. The report reviews several practices whose evidence came
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from the domains of commercial aviation, nuclear safety, and aerospace, and the disciplines of

human factors engineering and organizational theory. Such practices include root cause analysis,

computerized physician order entry and decision support, automated medication dispensing

systems, bar coding technology, aviation-style preoperative checklists, promoting a “culture of

safety,” crew resource management, the use of simulators in training, and integrating human

factors theory into the design of medical devices and alarms. In reviewing these practices, the

research team sought to be flexible regarding standards of evidence, and included research

evidence that would not have been considered for medical interventions. For example, the

randomized trial that is appropriately hailed as the “gold standard” in clinical medicine is not

used in aviation, as this design would not capture all relevant information. Instead, detailed case

studies and industrial engineering research approaches are utilized.

Methodology

To facilitate identification and evaluation of potential patient safety practices, the

Editorial Board divided the content for the project into different domains. Some cover “content

areas,” including traditional clinical areas such as adverse drug events, nosocomial infections,

and complications of surgery, but also less traditional areas such as fatigue and information

transfer. Other domains consist of practices drawn from broad (primarily nonmedical)

disciplines likely to contain promising approaches to improving patient safety (e.g., information

technology, human factors research, organizational theory). Once this list was created—with

significant input from patient safety experts, clinician–researchers, AHRQ, and the NQF Safe

Practices Committee—the editors selected teams of authors with expertise in the relevant subject

matter and/or familiarity with the techniques of evidence-based review and technology appraisal.

The authors were given explicit instructions regarding search strategies for identifying

safety practices for evaluation (including explicit inclusion and exclusion criteria) and criteria for

assessing each practice’s level of evidence for efficacy or effectiveness in terms of study design

and study outcomes. Some safety practices did not meet the inclusion criteria because of the

paucity of evidence regarding efficacy or effectiveness but were included in the report because

an informed reader might reasonably expect them to be evaluated or because of the depth of

public and professional interest in them. For such high profile topics (such as bar coding to

prevent misidentifications), the researchers tried to fairly present the practice’s background, the

experience with the practice thus far, and the evidence (and gaps in the evidence) regarding the

practice’s value.

For each practice, authors were instructed to research the literature for information on:

• prevalence of the problem targeted by the practice;

• severity of the problem targeted by the practice;

• the current utilization of the practice;

• evidence on efficacy and/or effectiveness of the practice;

• the practice’s potential for harm;

• data on cost, if available; and

• implementation issues.

The report presents the salient elements of each included study (e.g., study design,

population/setting, intervention details, results), and highlights any important weaknesses and
4

biases of these studies. Authors were not asked to formally synthesize or combine the evidence

across studies (e.g., perform a meta-analysis) as part of their task.

The Editorial Board and the Advisory Panel reviewed the list of domains and practices to

identify gaps in coverage. Submitted chapters were reviewed by the Editorial Board and revised

by the authors, aided by feedback from the Advisory Panel. Once the content was finalized, the

editors analyzed and ranked the practices using a methodology summarized below.

Summarizing the Evidence and Rating the Practices

Because the report is essentially an anthology of a diverse and extensive group of patient

safety practices with highly variable relevant evidence, synthesizing the findings was

challenging, but necessary to help readers use the information. Two of the most obvious uses for

this report are: 1) to inform efforts of providers and health care organizations to improve the

safety of the care they provide, and 2) to inform AHRQ, other research agencies, and

foundations about potential fruitful investments for their research support. Other uses of the

information are likely. In fact, the National Quality Forum plans to use this report to help

identify a list of patient safety practices that consumers and others should know about as they

choose among the health care provider organizations to which they have access.

In an effort to assist both health care organizations interested in taking substantive

actions to improve patient safety and research funders seeking to spend scarce resources wisely,

AHRQ asked the EPC to rate the evidence and rank the practices by opportunity for safety

improvement and by research priority. This report, therefore, contains two lists. 

To create these lists, the editors aimed to separate the practices that are most promising or

effective from those that are least so on a range of dimensions, without implying any ability to

calibrate a finely gradated scale for those practices in between. The editors also sought to

present the ratings in an organized, accessible way while highlighting the limitations inherent in

their rating schema. Proper metrics for more precise comparisons (e.g., cost-effectiveness

analysis) require more data than are currently available in the literature.

Three major categories of information were gathered to inform the rating exercise:

• Potential Impact of the Practice: based on prevalence and severity of the patient

safety target, and current utilization of the practice;

• Strength of the Evidence Supporting the Practice: including an assessment of the

relative weight of the evidence, effect size, and need for vigilance to reduce any

potential negative collateral effects of the practice; and

• Implementation: considering costs, logistical barriers, and policy issues.

For all of these data inputs into the practice ratings, the primary goal was to find the best

available evidence from publications and other sources. Because the literature has not been

previously organized with an eye toward addressing each of these areas, most of the estimates

could be improved with further research, and some are informed by only general and somewhat

speculative knowledge. In the summaries, the editors have attempted to highlight those

assessments made with limited data.

The four-person editorial team independently rated each of the 79 practices using general

scores (e.g., High, Medium, Low) for a number of dimensions, including those italicized in the
5

section above. The editorial team convened for 3 days in June, 2001 to compare scores, discuss

disparities, and come to consensus about ratings for each category.

In addition, each member of the team considered the totality of information on potential

impact and support for a practice to score each of these factors on a 0 to 10 scale (creating a

“Strength of the Evidence” list). For these ratings, the editors took the perspective of a leader of

a large health care enterprise (e.g., a hospital or integrated delivery system) and asked the

question, “If I wanted to improve patient safety at my institution over the next 3 years and

resources were not a significant consideration, how would I grade this practice?” For this

rating, the Editorial Board explicitly chose not to formally consider the difficulty or cost of

implementation in the rating. Rather, the rating simply reflected the strength of the evidence

regarding the effectiveness of the practice and the probable impact of its implementation on

reducing adverse events related to health care exposure. If the patient safety target was rated as

“High” impact and there was compelling evidence (i.e., “High” relative study strength) that a

particular practice could significantly reduce (e.g., “Robust” effect size) the negative

consequences of exposure to the health care system (e.g., hospital-acquired infections), raters

were likely to score the practice close to 10. If the studies were less convincing, the effect size

was less robust, or there was a need for a “Medium” or “High” degree of vigilance because of

potential harms, then the rating would be lower.

At the same time, the editors also rated the usefulness of conducting more research on

each practice, emphasizing whether there appeared to be questions that a research program might

have a reasonable chance of addressing successfully (creating a “Research Priority” list). Here,

they asked themselves, “If I were the leader of a large agency or foundation committed to

improving patient safety, and were considering allocating funds to promote additional research,

how would I grade this practice?” If there was a simple gap in the evidence that could be

addressed by a research study or if the practice was multifaceted and implementation could be

eased by determining the specific elements that were effective, then the research priority was

high. (For this reason, some practices are highly rated on both the “Strength of the Evidence”

and “Research Priority” lists.) If the area was one of high potential impact (i.e., large number of

patients at risk for morbid or mortal adverse events) and a practice had been inadequately

researched, then it would also receive a relatively high rating for research need. Practices might

receive low research scores if they held little promise (e.g., relatively few patients are affected by

the safety problem addressed by the practice or a significant body of knowledge already

demonstrates the practice’s lack of utility). Conversely, a practice that was clearly effective, low

cost, and easy to implement would not require further research and would also receive low

research scores.

In rating both the strength of the evidence and the research priority, the purpose was not

to report precise 0 to 10 scores, but to develop general “zones” or practice groupings. This is

important because better methods are available for making comparative ratings when the data

inputs are available. The relative paucity of the evidence dissuaded the editors from using a

more precise, sophisticated, but ultimately unfeasible, approach.
6

Clear Opportunities for Safety Improvement

The following 11 patient safety practices were the most highly rated (of the 79 practices

reviewed in detail in the full report and ranked in the Executive Summary Addendum, AHRQ

Publication No. 01-E057b) in terms of strength of the evidence supporting more widespread

implementation. Practices appear in descending order, with the most highly rated practices listed

first. Because of the imprecision of the ratings, the editors did not further divide the practices,

nor indicate where there were ties.

• Appropriate use of prophylaxis to prevent venous thromboembolism in

patients at risk;

• Use of perioperative beta-blockers in appropriate patients to prevent

perioperative morbidity and mortality;

• Use of maximum sterile barriers while placing central intravenous catheters

to prevent infections;

• Appropriate use of antibiotic prophylaxis in surgical patients to prevent

perioperative infections;

• Asking that patients recall and restate what they have been told during the

informed consent process;

• Continuous aspiration of subglottic secretions (CASS) to prevent ventilatorassociated pneumonia;

• Use of pressure relieving bedding materials to prevent pressure ulcers;

• Use of real-time ultrasound guidance during central line insertion to prevent

complications;

• Patient self-management for warfarin (CoumadinTM) to achieve appropriate

outpatient anticoagulation and prevent complications;

• Appropriate provision of nutrition, with a particular emphasis on early enteral

nutrition in critically ill and surgical patients; and

• Use of antibiotic-impregnated central venous catheters to prevent catheterrelated infections.

This list is generally weighted toward clinical rather than organizational matters, and

toward care of the very, rather than the mildly or chronically ill. Although more than a dozen

practices considered were general safety practices that have been the focus of patient safety

experts for decades (i.e., computerized physician order entry, simulators, creating a “culture of

safety,” crew resource management), most research on patient safety has focused on more

clinical areas. The potential application of practices drawn from outside health care has excited

the patient safety community, and many such practices have apparent validity. However, clinical

research has been promoted by the significant resources applied to it through Federal,

foundation, and industry support. Since this study went where the evidence took it, more clinical

practices rose to the top as potentially ready for implementation. 
7

Clear Opportunities for Research

Until recently, patient safety research has had few champions, and even fewer champions

with resources to bring to bear. The recent initiatives from AHRQ and other funders are a

promising shift in this historical situation, and should yield important benefits.

In terms of the research agenda for patient safety, the following 12 practices rated most

highly, as follows:

• Improved perioperative glucose control to decrease perioperative

infections;

• Localizing specific surgeries and procedures to high volume centers;

• Use of supplemental perioperative oxygen to decrease perioperative

infections;

• Changes in nursing staffing to decrease overall hospital morbidity and

mortality;

• Use of silver alloy-coated urinary catheters to prevent urinary tract

infections;

• Computerized physician order entry with computerized decision support

systems to decrease medication errors and adverse events primarily due to

the drug ordering process;

• Limitations placed on antibiotic use to prevent hospital-acquired

infections due to antibiotic-resistant organisms;

• Appropriate use of antibiotic prophylaxis in surgical patients to prevent

perioperative infections;

• Appropriate use of prophylaxis to prevent venous thromboembolism in

patients at risk;

• Appropriate provision of nutrition, with a particular emphasis on early

enteral nutrition in critically ill and post-surgical patients;

• Use of analgesics in the patient with an acutely painful abdomen without

compromising diagnostic accuracy; and

• Improved handwashing compliance (via education/behavior change; sink

technology and placement; or the use of antimicrobial washing

substances).

Of course, the vast majority of the 79 practices covered in this report would benefit from

additional research. In particular, some practices with longstanding success outside of medicine

(e.g., promoting a culture of safety) deserve further analysis, but were not explicitly ranked due

to their unique nature and the present weakness of the evidentiary base in the health care

literature.
8

Conclusions

This report represents a first effort to approach the field of patient safety through the lens

of evidence-based medicine. Just as To Err is Human sounded a national alarm regarding patient

safety and catalyzed other important commentaries regarding this vital problem, this review

seeks to plant a seed for future implementation and research by organizing and evaluating the

relevant literature. Although all those involved tried hard to include all relevant practices and to

review all pertinent evidence, inevitably some of both were missed. Moreover, the effort to

grade and rank practices, many of which have only the beginnings of an evidentiary base, was

admittedly ambitious and challenging. It is hoped that this report provides a template for future

clinicians, researchers, and policy makers as they extend, and inevitably improve upon, this

work.

In the detailed reviews of the practices, the editors have tried to define (to the extent

possible from the literature) the associated costs—financial, operational, and political. However,

these considerations were not factored into the summary ratings, nor were judgments made

regarding the appropriate expenditures to improve safety. Such judgments, which involve

complex tradeoffs between public dollars and private ones, and between saving lives by

improving patient safety versus doing so by investing in other health care or non-health care

practices, will obviously be critical. However, the public reaction to the IOM report, and the

media and legislative responses that followed it, seem to indicate that Americans are highly

concerned about the risks of medical errors and would welcome public and private investment to

decrease them. It seems logical to infer that Americans value safety during a hospitalization just

as highly as safety during a transcontinental flight.
Evidence Report
10
11

PART I. OVERVIEW

Chapter 1. An Introduction to the Report

1.1. General Overview

1.2. How to Use this Report

1.3. Acknowledgments

Chapter 2. Drawing on Safety Practices from Outside Health Care

Chapter 3. Evidence-based Review Methodology
12
13

Chapter 1. An Introduction to the Report

1.1. General Overview

The Institute of Medicine’s (IOM) report, To Err is Human: Building a Safer Health

System,

1

 highlighted the risks of medical care in the United States. Although its prose was

measured and its examples familiar to many in the health professions (for example, the studies

estimating that up to 98,000 Americans die each year from preventable medical errors were a

decade old), the report shocked the sensibilities of many Americans. More importantly, the

report undermined the fundamental trust that many previously had in the health care system.

The IOM report prompted a number of legislative and regulatory initiatives designed to

document errors and begin the search for solutions. These initiatives were further catalyzed by a

second IOM report entitled Crossing the Quality Chasm: A New Health System for the 21st

Century,

2

 which highlighted safety as one of the fundamental aims of an effective system. But

Americans, who now wondered whether their next health care encounter might harm rather than

help them, began to demand concerted action.

Making Health Care Safer represents an effort to determine what it is we might do in an

effort to improve the safety of patients. In January 2001, the Agency for Healthcare Research

and Quality (AHRQ), the Federal agency taking the lead in studying and promoting patient

safety, commissioned the UCSF-Stanford Evidence-based Practice Center (EPC) to review the

literature as it pertained to improving patient safety. In turn, the UCSF-Stanford EPC engaged 40

authors at 11 institutions around the United States to review more than 3000 pieces of literature

regarding patient safety practices. Although AHRQ expected that this evidence-based review

would have multiple audiences, the National Quality Forum (NQF)—a public-private partnership

formed in the Clinton Administration to promote a national quality agenda—was particularly

interested in the results as it began its task of recommending and implementing patient safety

practices supported by the evidence.

A Definition of “Patient Safety Practices”

One of our first tasks was to define “patient safety practices” in a manner that would

allow us and our reviewers to assess the relevant evidence. Given our task—producing a full

report in less than six months—a complete review of all practices associated with improving

health care quality was both impossible and off-point. Working closely with AHRQ and NQF,

we chose the following definition:

A Patient Safety Practice is a type of process or structure whose application reduces

the probability of adverse events resulting from exposure to the health care system

across a range of diseases and procedures.

A few elements of the definition deserve emphasis. First, our focus on processes and

structure allowed us to emphasize changing the system to make it safer rather than targeting and

removing individual “bad apples.” We recognize that when individuals repeatedly perform

poorly and are unresponsive to education and remediation, action is necessary. Nevertheless,

there is virtual unanimity among patient safety experts that a focus on systemic change will be

far more productive than an emphasis on finding and punishing poor performers.

Second, looking at crosscutting diseases and procedures allowed us to distinguish patient

safety activities from more targeted quality improvement practices. Admittedly, this

dichotomization is imprecise. All would agree that a practice that makes it less likely that a
14

patient will receive the wrong medication or have the wrong limb amputated is a patient safety

practice. Most would also agree that practices designed to increase the use of beta-blockers in

patients admitted to the hospital after myocardial infarction or to improve the technical

performance of hernia repair would be quality improvement strategies rather than patient safety

practices. When there was a close call, we generally chose to be inclusive. For example, we

included practices designed to increase the rate of appropriate prophylaxis against venous

thromboembolism, the appropriateness of pain management, and the ascertainment of patient

preferences regarding end-of-life care. We recognize that these practices blur the line somewhat

between safety and quality, but we believe that they are reasonable examples of ways to address

potential patient safety hazards.

Third, we realized it would be impossible to review every potential safety practice and

recognized that some gaps in the evidence were inevitable, so at times we reviewed illustrative

examples that might be broadly generalizable. For example:

• Methods to avoid misread radiographs (Chapter 35); where the content could

be relevant to analogous efforts to avoid misread electrocardiograms or

laboratory studies

• Decreasing the risk of dangerous drugs (Chapter 9), where the focus was on

anticoagulants, but similar considerations might be relevant for chemotherapy

and other high-risk drugs

• Localizing care to specialized providers reviews geriatric units and

intensivists (Chapters 30 and 38), but similar evidence may be relevant for the

rapidly growing field of hospitalists3-5

• The use of ultrasound guidance for central line placement (Chapter 21); the

premise (decreasing the risk of an invasive procedure through radiologic

localization) may also be relevant for ultrasound guidance while performing

other challenging procedures, such as thoracentesis

A Focus on Hospital Care

Most of the literature regarding medical errors has been drawn from hospital care.6-22 For

example, the two seminal studies on medical error22,23 from which the oft-cited extrapolations of

yearly deaths from medical error were derived, have highlighted the risks of inpatient care. We

applaud recent studies examining the risks of errors in the ambulatory setting24 but believe that

the hospital is an appropriate initial focus for an evidence-based review because the risks

associated with hospitalization are high, strategies for improvement are better documented, and

the importance of patient trust is paramount.

That said, the reader will see that we allowed the evidence to take us to other sites of

care. For example, although much of the literature regarding the occurrence and prevention of

adverse drug events is hospital-based, more recent literature highlights outpatient issues and is

included in this review. An example is the chapter on decreasing the risk of anticoagulant

treatment (Chapter 9), in which two of the most promising practices involve outpatient

anticoagulation clinics and patient self-monitoring at home. Similarly, strategies to prevent falls

or pressure ulcers are relevant to nursing home patients as well as those in hospitals, and many

studies that shed light on these issues come from the former setting.
15

The Evidence

Chapter 3 describes our strategy for evidence review. As in other evidence-based

reviews, we set the bar high. One would not want to endorse a practice unsupported by evidence,

nor withhold one substantiated by a high level of proof. In the end, we aimed to identify

practices whose supporting evidence was so robust that immediate widespread implementation

would lead to major improvements in patient safety. Additionally, we hoped to identify several

practices whose promise merited a considerable investment in additional research, but whose

evidentiary base was insufficient for immediate endorsement. The results of this effort are

summarized in Part V of the Report.

Readers familiar with the state of the evidence regarding quality improvement in areas

where this has been a research priority (eg, cardiovascular care) may be surprised and even

disappointed by the paucity of high quality evidence for many patient safety practices. The field

is young. Just as there had been little public recognition of the risks of health care prior to the

first IOM report, there has been relatively little attention paid to such risks—and strategies to

mitigate them—among health professionals and researchers. Nevertheless, we found a number of

practices supported by high quality evidence for which widespread implementation would save

many thousands of lives.

Moreover, there are important methodologic reasons why research in patient safety is

particularly challenging. First is the problem of blinding. The physician who has begun to use a

new computerized order entry system cannot be blinded to the intervention or its purpose.

Second, it is sometimes difficult to measure important outcomes. As in aviation, enormous

benefits can be reaped from analyzing “near misses” (with no ultimate harm to patients),25,26 and

yet these outcomes cannot be reliably counted in the absence of potentially obtrusive, and often

very expensive observation. Third, many effective practices are multidimensional, and sorting

out precisely which part of the intervention works is often quite challenging. Fourth, many of the

patient safety problems that generate the most concern (wrong-site surgery, for example) are

probably uncommon. This makes demonstrating the success of a “safety practice” in a

statistically meaningful manner with respect to outcomes all but impossible.

Finally, establishing firm epidemiologic links between presumed (and accepted) causes

and adverse events is critical, and frequently difficult. For instance, verbal orders from doctors to

nurses are regarded as a cause of medication errors almost as matter of dogma, with many

hospitals prohibiting or strongly discouraging this practice except in emergency situations.27 Yet,

the one study that we could identify that specifically and comprehensively addressed this issue28

actually reported fewer errors among verbal medication orders compared with written medication

orders. A similar relationship might be found studying other intuitively plausible “risk factors”

for errors, such as “fatigue.” Because many health care providers work long hours and/or late at

night, analyses of errors will commonly reveal fatigued providers. The question is whether or not

fatigue is over-represented among situations that lead to errors. As discussed in Chapter 46, the

evidence supporting fatigue as a contributor to adverse events is surprisingly mixed. The point is

not that the problem of long work-hours should be ignored, but rather that strong epidemiologic

methods need to be applied before concluding that an intuitive cause of errors is in fact causal.

These methodologic issues are further explored in Chapters 3 (methods for analyzing the

individual practices) and 56 (methods for summarizing the overall evidence).

Improving patient safety is a team effort, and the playbook is often drawn from fields

outside of health care. Most medical errors cannot be prevented by perfecting the technical work

of individual doctors, nurses or pharmacists. Improving patient safety often involves the
16

coordinated efforts of multiple members of the health care team, who may adopt strategies from

outside health care. Thus, our teams of authors and advisors included physicians, pharmacists,

nurses, and experts from non-medical fields. The literature we reviewed was often drawn from

journals, books, or Web sites that will not be on most doctors’ reading lists. We reviewed several

promising practices whose evidence came from the domains of commercial aviation, nuclear

safety, and aerospace, and the disciplines of human factors engineering and organizational

theory. In reviewing these practices, we tried to be flexible regarding standards of evidence. For

example, the randomized trial that is appropriately hailed as the “gold standard” in health care is

rarely used in aviation, which instead relies on analyses of detailed case studies and industrial

engineering research approaches. (Examples and additional discussion of this issue can be found

in Chapter 2.)

We also limited our discussion to the existing practices, recognizing that future

technology may make the ones we reviewed obsolete. For example, much of the struggle to find

safe ways to administer warfarin (Chapter 9) would be rendered moot by the development of a

much safer, but equally effective oral anticoagulant that did not require monitoring. Similarly,

the evidence regarding changing the flooring of rooms to decrease falls (Subchapter 26.4)

indicated that present options may decrease the harm from falls but actually increase their rate.

Clearly, a better surface would make falls both less likely and less harmful. Such a surface has

not yet been tested.

Finally, we have tried to define (to the extent possible from the literature) the costs—

financial, operational, and political—associated with the patient safety practices we considered.

However, we have not made judgments regarding the appropriate expenditures to improve

safety. These judgments, which involve complex tradeoffs between public dollars and private

ones, and between saving lives by improving patient safety versus doing so by investing in other

health care or non-health care practices, will obviously be critical. However, the public reaction

to the IOM report, and the media and legislative responses that followed it, seem to indicate that

Americans are highly concerned about the risks of medical errors and would welcome public and

private investment to decrease them. It seems logical to infer that Americans value safety during

a hospitalization just as highly as safety during a transcontinental flight.

The Decision to Include and Exclude Practices

The patient safety/quality interface was only one of several areas that called for

judgments regarding which practices to include or exclude from the Report. In general (and quite

naturally for an evidence-based review), we excluded those practices for which we found little or

no supporting evidence. However, we recognize that patient safety is of great public and

professional interest, and that the informed reader might expect to find certain topics in such a

review. Therefore, we included several areas notwithstanding their relatively meager evidentiary

base. For such high profile topics (such as bar coding to prevent misidentifications, Subchapter

43.1), we tried to fairly present the practice’s background, the experience with the practice thus

far, and the evidence (and gaps in the evidence) regarding its value. In many of these cases, we

end by encouraging additional study or demonstration projects designed to prove whether the

practices live up to their promise.

Conversely, another very different group of practices lacked evidence and were excluded

from the review. These practices were characterized by their largely self-evident value (in

epidemiologic terms, their “face validity”). For example, large randomized studies of the

removal of concentrated potassium chloride from patient care floors surely are not necessary in

order to recommend this practice as a sensible way of preventing egregious errors that should
17

never occur. Although some of these types of practices were not included in this “evidencebased” Report, the reader should not infer their exclusion as a lack of endorsement.

A cautionary note is in order when considering such “obviously beneficial” practices.

Even an apparently straightforward practice like “signing the site” to prevent surgery or

amputation of the wrong body part may lead to unexpected opportunities for error. As mentioned

in Subchapter 43.2, some surgeons adopt the practice of marking the intended site, while others

mark the site to avoid. The clinical research literature furnishes enough examples of practices

that everyone “knew” to be beneficial but proved not to be (or even proved to be harmful) once

good studies were conducted (antiarrhythmic therapy for ventricular ectopy29 or hormone

replacement therapy to prevent cardiac deaths,30 for example) that it is reasonable to ask for

high-quality evidence for most practices. This is particularly true when practices are expensive,

complex to implement, or carry their own risks.

Other Content Issues

There may appear to some readers to be an inordinate focus on clinical issues versus

more general patient safety practices. In this and other matters, we went where the evidence took

us. Although more than a dozen chapters of the Report consider general safety practices that

have been the focus of many patient safety experts for decades (ie, computerized order entry,

simulators, crew resource management), most research on patient safety, in fact, has focused on

more clinical matters. It is likely that some of this is explained by the previous “disconnect”

between research in patient safety and its application. We are hopeful that the Report helps to

bridge this gap. We also think it likely that clinical research has been promoted by the significant

resources applied to it through Federal, foundation, and industry support. Until recently, patient

safety research has had few champions, and even fewer champions with resources. The recent

initiatives from AHRQ and other funders are a promising shift in this historical situation, and

should yield important benefits.

The reader will notice that there is relatively little specific coverage of issues in

pediatrics, obstetrics, and psychiatry. Most of the patient safety practices we reviewed have

broad applicability to those fields as well as larger fields such as surgery and medicine. Much of

the research in the former fields was too disease-specific to include in this volume. For example,

practices to improve the safety of childbirth, although exceptionally important, were excluded

because they focused on the care of patients with a single “condition,” just as we excluded

research focused specifically on the care of patients with pneumonia or stroke.

Readers may also be surprised by the relatively small portion of the Report devoted to the

prevention of high-profile and “newsworthy” errors. Even if much of the national attention to

patient safety stemmed from concerns about wrong-site surgery or transfusion mix-ups, in fact

these are not the dominant patient safety problems today. If widespread use of hip protectors

(Subchapter 26.5) leads to a marked decrease in injuries from patient falls, implementing this

safety practice would be more important than preventing the few wrong-site surgeries each year,

although the former seem far less likely to garner attention in a tabloid.

Conclusions

Making Health Care Safer represents a first effort to approach the field of patient safety

through the lens of evidence-based medicine. Just as To Err is Human sounded a national alarm

regarding patient safety and catalyzed other important commentaries regarding this vital

problem, this review is a germinal effort to mine the relevant literature. Although we and the

authors tried hard to include all relevant practices and to review all pertinent evidence, we
18

inevitably missed some of both. Moreover, our effort to rank practices (Part V), many of which

have only the beginnings of an evidentiary base, was admittedly ambitious and challenging. We

hope that the Report provides a template for future clinicians, researchers, and policy makers as

they extend, and inevitably improve upon, our work.

1.2. How to Use this Report

Organizational Framework

This document is divided into five parts:

Part I – The overview introduces many of the methodologic, content, and policy issues.

Part II – We describe, and present the evidence regarding 2 practices that are used to report and

respond to patient safety problems: incident reporting and root cause analysis. Since both these

“practices” have relevance for all of the patient safety targets and practices covered in Part III,

we neither grade them nor rank them.

Part III – In 45 chapters, we review the evidence regarding the utility of 79 patient safety

practices. Each chapter is structured in a standard fashion, as follows:

• Background – of the patient safety problem and the practice;

• Practice Description – in which we try to present the practice at a level of

detail that would allow a reader to determine the practice’s applicability to

their setting;

• Prevalence and Severity of the Target Safety Problem – Here, we try to

answer the following questions: How common is the safety problem the

practice is meant to address? How often does the problem lead to harm? How

bad is the harm when it occurs?;

• Opportunities for Impact – In this section, we consider the present-day use of

the patient safety practice. For example, we found that the use of “unit-dose”

drug dispensing was quite common in US hospitals, and thus the opportunity

to make an impact with wider dissemination of this practice was relatively

low. Conversely, computerized physician order entry is still relatively

uncommon, and therefore (assuming it is effective), its widespread

implementation could have a far larger impact;

• Study Designs – We review the designs of the major studies evaluating the

practice. Similarly, Study Outcomes looks at the kinds of outcomes (eg,

adverse drug events, surgical complications, mortality) that were considered.

Our criteria for grading the evidence related to both design and outcomes

(more information on other methodologic issues appears in Chapter 3);

• Evidence for Effectiveness of the Practice – Here, the authors summarize the

findings of the studies and comment on any methodologic concerns that might

effect the strength of these findings. This section is often accompanied by

tables summarizing the studies and their findings;
19

• Potential for Harm – Many practices that are effective in improving patient

safety nonetheless carry the potential for harm. More widespread use of

antibiotic prophylaxis or antibiotic-impregnated urinary or vascular catheters

could prevent individual hospital-acquired infections yet breed antibiotic

resistance. Increasing the use of barrier precautions could also prevent

infections, but might lead caregivers to visit patients less often. These sections

do not imply that harm is inevitable; rather they highlight the issues that

require vigilance during the implementation of effective practices;

• Costs and Implementation – Here we consider the costs and other challenges

of implementing the practice. We tried to uncover data related to the true costs

of implementation (How much does an automatic drug dispensing machine

cost a pharmacy?), but also considered some of the potential offsets when

there were data available. We also considered issues of feasibility: How much

behavior change would be necessary to implement the practice? Would there

be major political concerns or important shifts in who pays for care or is

compensated for providing it? We tried not to assign values to such issues, but

rather to present them so that policy makers could consider them; and

• Comment – Here, the authors highlight the state of the evidence, elucidate key

implementation issues, and define a potential research agenda.

Part IV – In many ways a mirror of Part II, Part IV considers the ways in which patient safety

practices can be implemented. The evidence is reviewed, and some of the benefits and

limitations of various strategies are analyzed. As with Part II, we neither grade nor rank these

“practices” in Part V since each of these strategies can be applied to most of the patient safety

targets and practices covered in Part III.

Part V – Here we analyze the practices. Using methods described in Chapter 56, we synthesize

the evidence in Part III to grade and rank the patient safety practices across two major

dimensions:

• Does the evidence support implementation of the practice to improve patient safety?

• Does the evidence support additional research into the practice?

Tips for Users of the Report

We envision that this evidence-based report of patient safety practices will be useful to a

wide audience.

Policy makers may use its contents and recommendations to promote or fund the

implementation of certain practices. Similarly, local health care organization leaders (including

leaders of hospitals, medical groups, or integrated delivery systems) may use the data and

analysis to choose which practices to consider implementing or further promoting at their

institutions.

Researchers will identify a wealth of potential research opportunities. This document is,

in many ways, a road map for future research into patient safety. Those who fund research,

including (but not limited to) AHRQ, which sponsored this report, will find literally dozens of

areas ripe for future studies. In some cases, such studies may be expensive randomized

controlled trials, while other practices may require a simple meta-analysis or cost-effectiveness

analysis to tip the scales toward or away from recommending a practice.
20

Clinicians and trainees will, we hope, find the material both interesting and relevant to

their practices. One of the salutary consequences of the IOM’s reports has been their impact on

the attitudes of our future health care providers. We have noticed at our institutions that students

and post-graduate trainees in medicine, nursing, and pharmacy are increasingly taking a systems

approach to health care. Several of us have heard medical residents refer to issues as “patient

safety problems” that beg for a “systems solution” over the past two years, terms that were

absent from the medical ward a few years earlier. Clinicians must be part of the solutions to

patient safety problems, and their increasing interest in the field is an exceedingly hopeful sign.

Finally, although not primarily written for patients and their families, we recognize the

broad public interest in, and concern about patient safety and believe that much of the material

will be compelling and potentially useful to the public. For years quality advocates have

lamented the relatively small impact that “quality report cards” appear to have on patients’

choices of health care providers and institutions. One study demonstrated that patients were more

likely to respond to a newspaper report of an egregious error than such quality report cards.31

These data indicate that patients may be interested in knowing whether their institutions,

providers, and health plans are proactive in implementing practices that demonstrably decrease

the risk of adverse events. Also, any general reader is likely to come away from this Report with

heightened sensitivity to the unique challenges that the health care industry—which aims to

provide compassionate, individualized care in a dynamic, organizationally and politically

complex, and technologically fluid environment—faces in improving safety, and the significant

strides that have already been made. Continued improvement will require the infusion of

substantial resources, and the public debate about their source, quantity, and target is likely to be

lively and very important.

1.3. Acknowledgments

We are grateful to our authors, whose passion for the evidence overcame the tremendous

time pressure driven by an unforgiving timeline. They succumbed to our endless queries, as

together we attempted to link the literature from a variety of areas into an evidence-based

repository whose presentation respected an overarching framework, notwithstanding the variety

of practices reviewed. Our Managing Editor, Amy J. Markowitz, JD, edited the manuscript

with incredible skill and creativity. Each part was reviewed and improved multiple times because

of her unending dedication to the project. Susan B. Nguyen devoted countless hours assisting

the team in every imaginable task, and was critical in keeping the project organized and on track.

Invaluable editorial and copyediting assistance was provided by Kathleen Kerr, Talia Baruth,

and Mary Whitney. We thank Phil Tiso for helping produce the electronic version of the

Report. We also thank A. Eugene Washington, MD, MSc, Director of the UCSF-Stanford

Evidence-based Practice Center, for his guidance and support.

We were aided by a blue-ribbon Advisory Panel whose suggestions of topics, resources,

and ideas were immensely helpful to us throughout the life of the project. Given the time

constraints, there were doubtless many constructive suggestions that we were unable to

incorporate into the Report. The responsibility for such omissions is ours alone. We want to

recognize the important contribution of our advisors to our thinking and work. The Advisory

Panel’s members are:

• David M. Gaba, MD, Director, Patient Safety Center of Inquiry at Veterans

Affairs Palo Alto Health Care System, Professor of Anesthesia, Stanford

University School of Medicine
21

• John W. Gosbee, MD, MS, Director of Patient Safety Information Systems,

Department of Veterans Affairs National Center for Patient Safety

• Peter V. Lee, JD, President and Chief Executive Officer, Pacific Business

Group on Health

• Arnold Milstein, MD, MPH, Medical Director, Pacific Business Group on

Health; National Health Care Thought Leader, William M. Mercer, Inc.

• Karlene H. Roberts, PhD, Professor, Walter A. Haas School of Business,

University of California, Berkeley

• Stephen M. Shortell, PhD, Blue Cross of California Distinguished Professor

of Health Policy and Management and Professor of Organization Behavior,

University of California, Berkeley

We thank the members of the National Quality Forum’s (NQF) Safe Practices

Committee, whose co-chairs, Maureen Bisognano and Henri Manasse, Jr., PhD, ScD, and

members helped set our course at the outset of the project. NQF President and Chief Executive

Officer Kenneth W. Kizer, MD, MPH, Vice President Elaine J. Power, and Program Director

Laura N. Blum supported the project and coordinated their committee members’ helpful

suggestions as the project proceeded. We appreciate their patience during the intensive research

period as they waited for the final product.

Finally, we are indebted to the Agency for Healthcare Research and Quality (AHRQ),

which funded the project and provided us the intellectual support and resources needed to see it

to successful completion. Jacqueline Besteman, JD of AHRQ’s Center for Practice and

Technology Assessment, and Gregg Meyer, MD, and Nancy Foster, both from AHRQ’s Center

for Quality Improvement and Patient Safety, were especially important to this project. John

Eisenberg, MD, MBA, AHRQ’s Administrator, was both a tremendous supporter of our work

and an inspiration for it.

The Editors

San Francisco and Palo Alto, California

June, 2001

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8. Bosk CL. Forgive and remember : managing medical failure. Chicago: University of

Chicago Press; 1979.

9. Abramson NS, Wald KS, Grenvik AN, Robinson D, Snyder JV. Adverse occurrences in

intensive care units. JAMA. 1980;244:1582-1584.

10. Barker KN, Mikeal RL, Pearson RE, Illig NA, Morse ML. Medication errors in nursing

homes and small hospitals. Am J Hosp Pharm. 1982;39:987-991.

11. Cooper JB, Newbower RS, Kitz RJ. An analysis of major errors and equipment failures in

anesthesia management: considerations for prevention and detection. Anesthesiology.

1984;60:34-42.

12. Rubins HB, Moskowitz MA. Complications of care in a medical intensive care unit. J Gen

Intern Med. 1990;5:104-109.

13. Silber JH, Williams SV, Krakauer H, Schwartz JS. Hospital and patient characteristics

associated with death after surgery. A study of adverse occurrence and failure to rescue.

Med Care. 1992;30:615-629.

14. Runciman WB, Sellen A, Webb RK, Williamson JA, Currie M, Morgan C, et al. The

Australian Incident Monitoring Study. Errors, incidents and accidents in anaesthetic

practice. Anaesth Intensive Care. 1993;21:506-519.

15. Donchin Y, Gopher D, Olin M, Badihi Y, Biesky M, Sprung CL, et al. A look into the

nature and causes of human errors in the intensive care unit. Critical Care Medicine.

1995;23:294-300.

16. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse

drug events and potential adverse drug events. Implications for prevention. ADE

Prevention Study Group. JAMA. 1995;274:29-34.

17. Dean BS, Allan EL, Barber ND, Barker KN. Comparison of medication errors in an

American and a British hospital. Am J Health Syst Pharm. 1995;52:2543-2549.

18. Wilson RM, Runciman WB, Gibberd RW, Harrison BT, Newby L, Hamilton JD. The

Quality in Australian Health Care Study. Med J Aust. 1995;163:458-471.

19. Andrews LB, Stocking C, Krizek T, Gottlieb L, Krizek C, Vargish T, et al. An alternative

strategy for studying adverse events in medical care. Lancet. 1997;349:309-313.

20. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in

hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA.

1997;277:301-306.

21. Lesar TS, Lomaestro BM, Pohl H. Medication-prescribing errors in a teaching hospital. A

9-year experience. Arch Intern Med. 1997;157:1569-1576.

22. Thomas EJ, Studdert DM, Burstin HR, Orav EJ, Zeena T, Williams EJ, et al. Incidence and

types of adverse events and negligent care in Utah and Colorado. Med Care. 2000;38:261-

271.
23

23. Brennan TA, Leape LL, Laird NM, Hebert L, Localio AR, Lawthers AG, et al. Incidence

of adverse events and negligence in hospitalized patients. Results of the Harvard Medical

Practice Study I. N Engl J Med. 1991;324:370-376.

24. Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, et al. Drug

complications in outpatients. J Gen Intern Med. 2000;15:149-154.

25. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical

near miss reporting systems. BMJ. 2000;320:759-763.

26. Leape LL. Reporting of medical errors: time for a reality check. Qual Health Care.

2000;9:144-145.

27. Dahl FC, Davis NM. A survey of hospital policies on verbal orders. Hosp Pharm.

1990;25:443-447.

28. West DW, Levine S, Magram G, MacCorkle AH, Thomas P, Upp K. Pediatric medication

order error rates related to the mode of order transmission. Arch Pediatr Adolesc Med.

1994;148:1322-1326.

29. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of

arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression

Trial (CAST) Investigators. N Engl J Med. 1989;321:406-412.

30. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of

estrogen plus progestin for secondary prevention of coronary heart disease in

postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS)

Research Group. JAMA. 1998;280:605-613.

31. Mennemeyer ST, Morrisey MA, Howard LZ. Death and reputation: how consumers acted

upon HCFA mortality information. Inquiry. 1997;34:117-128.
24
25

Chapter 2. Drawing on Safety Practices from Outside Health Care

The medical profession’s previous inattention to medical error, along with other

publicized deficiencies (such as a notable lag in adopting sophisticated information technologies)

have invited unfavorable comparisons between health care and other complex industries.1-5 The

first of the two recent Institute of Medicine (IOM) reports on the quality of health care in

America, To Err is Human: Building a Safer Health System,3

 states that “health care is a decade

or more behind other high-risk industries in its attention to ensuring basic safety.” Consequently,

one of the goals of this project was to search these other industries for evidence-based safety

strategies that might be applied to health care.

The relatively short timeline of this project necessitated a focused approach to the search

for potentially applicable patient safety practices from non-health care writings. Fortunately,

many relevant practices have received at least some analysis or empirical study in the health care

literature. As a practical solution we present original articles from outside health care as

foundational and background material, rather than as a primary source of evidence. Specific

topics and practices reviewed in Making Health Care Safer that clearly derive from fields

outside health care include:

• Incident reporting (Chapter 4)

• Root cause analysis (Chapter 5)

• Computerized physician order entry and decision support as a means of

reducing medication errors (Chapter 6)

• Automated medication dispensing systems (Chapter 11)

• Bar coding technology to avoid misidentification errors (Subchapter 43.1)

• Aviation-style preoperative checklists for anesthesia equipment (Chapter 23

and Subchapter 41.3)

• Promoting a “culture of safety” (Chapter 40)

• Crew resource management, a model for teamwork training and crisis

response modeled after training approaches in aviation (Chapter 44)

• Simulators (of patients or clinical scenarios) as a training tool (Chapter 45)

• Human factors theory in the design of medical devices and alarms (Chapter

41)

Many readers may still wonder at the relative paucity of safety practices drawn from nonhealth care sources. While the headline-grabbing assessments of medicine’s safety have been

criticized by researchers and likely overstate the hazard to patients,6-8 it is undeniable that some

industries, most notably commercial aviation, have safety records far superior to that of health

care. One issue we faced in compiling this evidence-based review was the extent to which

specific practices could be identified as playing a direct and measurable role in this achievement.

Interestingly, the same issue—ascertaining a causative variable—arose in reviewing the

literature on anesthesia, likely the one field of medicine with a safety record that rivals aviation’s

(see also Chapter 56).
26

As outlined in Chapter 24, significant complications attributable to anesthesia have

decreased9-12 to the point that major morbidity and mortality are now too rare to serve as

practical endpoints for measuring the quality of anesthesia care, even in large multicenter

studies.13,14 In attempting to account for this decrease, however, it is very difficult to find

evidence supporting a causative role for even the most plausible candidates, such as widely

utilized intraoperative monitoring standards.15 In other words, while the field of anesthesia has

clearly made tremendous strides in improving patient safety over the past 50 years, it is hard to

discern a particular, isolated practice that accounts for the clear and dramatic secular change in

its safety. While at one level, a pragmatist might argue, “who cares, as long as it’s safe,” trying

to adopt the lessons of anesthesia (or for that matter aviation) to the rest of health care is made

more challenging by tenuous causality.

Some might argue that, rather than pinpointing specific practices to embrace from other

industries, health care institutions should emulate organizational models that promote safety in

complex, high-risk industries that manage to operate with high reliability.16 Analysis of detailed

and interesting case studies17-22 have fueled a school of thought known as high reliability theory,

whose proponents suggest a number of organizational features that likely reduce the risk of

“organizational accidents” and other hazards. A cogently argued alternative position, often called

normal accident theory, questions not only these prescriptions for organizational change, but

fundamentally challenges the idea of high reliability in certain kinds of complex, “tightly

coupled” organizations.23,24 These competing schools of thought offer interesting and valuable

insights into the ways that organizational strategies foster safety, while cautioning about the

ever-present threat of new sources of error that come with increasingly complex human and

technical organizations. Unfortunately, this rich literature does not permit ready synthesis within

the framework of evidence-based medicine, even using the less stringent standards we adopted in

evaluating non-medical literature (see Chapters 1 and 3).

Even the more engineering-oriented of the disciplines with potential relevance to patient

safety yielded a surprising lack of empirical evaluation of safety practices. For instance,

numerous techniques for “human error identification” and “error mode prediction” purport to

anticipate important errors and develop preventive measures prospectively.25-27 Their basic

approach consists of breaking down the task of interest into component processes, and then

assigning a measure of the likelihood of failure to each process. Many of the techniques

mentioned in the literature have received little detailed description25,26 and few have received

any formal validation (eg, by comparing predicted failures modes with observed errors).28,29

Even setting aside demands for validation, the impact of applying these techniques has not been

assessed. Total quality management and continuous quality improvement techniques were

championed as important tools for change in health care based on their presumed success in

other industries, but evaluations of their impact on health care have revealed little evidence of

success.30-33

In the end, we are left with our feet firmly planted in the middle of competing paradigms.

One argues that an evidence-based, scientific approach has served health care well and should

not be relaxed simply because a popular practice from a “safer” industry sounds attractive. The

other counters that medicine’s slavish devotion to the scientific and epidemiologic method has

placed us in a patient safety straightjacket, unable to consider the value of practices developed in

other fields because of our myopic traditions and “reality.”

We see the merits in both arguments. Health care clearly has much to learn from other

industries. Just as physicians must learn the “basic sciences” of immunology and molecular

biology, providers and leaders interested in making health care safer must learn the “basic
27

sciences” of organizational theory and human factors engineering. Moreover, the “cases”

presented on rounds should, in addition to classical clinical descriptions, also include the tragedy

of the Challenger and the successes of Motorola. On the other hand, an unquestioning embrace

of dozens of promising practices from other fields is likely to be wasteful, distracting, and

potentially dangerous. We are drawn to a dictum from the Cold War era—“Trust, but verify.”

References

1. Leape LL. Error in medicine. JAMA. 1994;272:1851-1857.

2. Chassin MR. Is health care ready for Six Sigma quality? Milbank Q. 1998;76:565-591,510.

3. Kohn L, Corrigan J, Donaldson M, editors. To Err Is Human: Building a Safer Health

System. Washington, DC: Committee on Quality of Health Care in America, Institute of

Medicine. National Academy Press; 2000.

4. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical

near miss reporting systems. BMJ. 2000;320:759-763.

5. Helmreich RL. On error management: lessons from aviation. BMJ. 2000;320:781-785.

6. Brennan TA. The Institute of Medicine report on medical errors–could it do harm? N Engl

J Med. 2000;342:1123-1125.

7. McDonald CJ, Weiner M, Hui SL. Deaths due to medical errors are exaggerated in Institute

of Medicine report. JAMA. 2000;284:93-95.

8. Sox HCJ, Woloshin S. How many deaths are due to medical error? Getting the number

right. Eff Clin Pract. 2000;3:277-283.

9. Phillips OC, Capizzi LS. Anesthesia mortality. Clin Anesth. 1974;10:220-244.

10. Deaths during general anesthesia: technology-related, due to human error, or unavoidable?

An ECRI technology assessment. J Health Care Technol. 1985;1:155-175.

11. Keenan RL, Boyan CP. Cardiac arrest due to anesthesia. A study of incidence and causes.

JAMA. 1985;253:2373-2377.

12. Eichhorn JH. Prevention of intraoperative anesthesia accidents and related severe injury

through safety monitoring. Anesthesiology. 1989;70:572-577.

13. Cohen MM, Duncan PG, Pope WD, Biehl D, Tweed WA, MacWilliam L, et al. The

Canadian four-centre study of anaesthetic outcomes: II. Can outcomes be used to assess the

quality of anaesthesia care? Can J Anaesth. 1992;39:430-439.

14. Moller JT, Johannessen NW, Espersen K, Ravlo O, Pedersen BD, Jensen PF, et al.

Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative events and

postoperative complications. Anesthesiology. 1993;78:445-453.

15. Orkin FK. Practice standards: the Midas touch or the emperor's new clothes?

Anesthesiology. 1989;70:567-571.

16. Reason J. Human error: models and management. BMJ. 2000;320:768-770.

17. Weick KE. Organizational culture as a source of high reliability. California management

review. 1987;29:112-127.

18. Roberts KH. Some characteristics of high reliability organizations. Berkeley, CA:

Produced and distributed by Center for Research in Management, University of California,

Berkeley Business School; 1988.

19. LaPorte TR. The United States air traffic control system : increasing reliability in the midst

of rapid growth. In: Mayntz R, Hughes TP, editors. The Development of Large technical

Systems. Boulder, CO: Westview Press; 1988.

20. Roberts KH. Managing High Reliability Organizations. California Management Review.

1990;32:101-113.
28

21. Roberts KH, Libuser C. From Bhopal to banking: Organizational design can mitigate risk.

Organizational Dynamics. 1993;21:15-26.

22. LaPorte TR, Consolini P. Theoretical and operational challenges of "high-reliability

organizations": Air-traffic control and aircraft carriers. International Journal of Public

Administration. 1998;21:847-852.

23. Perrow C. Normal accidents : Living with High-Risk Technologies. With a New Afterword

and a Postscript on the Y2K Problem. Princeton, NJ: Princeton University Press; 1999.

24. Sagan SD. The Limits of Safety: Organizations, Accidents and Nuclear Weapons.

Princeton, NJ: Princeton University Press; 1993.

25. Kirwan B. Human error identification techniques for risk assessment of high risk systems–

Part 1: Review and evaluation of techniques. Appl Ergon. 1998;29:157-177.

26. Kirwan B. Human error identification techniques for risk assessment of high risk systems–

Part 2: towards a framework approach. Appl Ergon. 1998;29:299-318.

27. Hollnagel E, Kaarstad M, Lee HC. Error mode prediction. Ergonomics. 1999;42:1457-

1471.

28. Kirwan B, Kennedy R, Taylor-Adams S, Lambert B. The validation of three human

reliability quantification techniques–THERP, HEART and JHEDI: Part II–Results of

validation exercise. Appl Ergon. 1997;28:17-25.

29. Stanton NA, Stevenage SV. Learning to predict human error: issues of acceptability,

reliability and validity. Ergonomics. 1998;41:1737-1756.

30. Blumenthal D, Kilo CM. A report card on continuous quality improvement. Milbank Q.

1998;76:625-48,511.

31. Gerowitz MB. Do TQM interventions change management culture? Findings and

implications. Qual Manag Health Care. 1998;6:1-11.

32. Shortell SM, Bennett CL, Byck GR. Assessing the impact of continuous quality

improvement on clinical practice: what it will take to accelerate progress. Milbank Q.

1998;76:593-624,510.

33. Shortell SM, Jones RH, Rademaker AW, Gillies RR, Dranove DS, Hughes EF, et al.

Assessing the impact of total quality management and organizational culture on multiple

outcomes of care for coronary artery bypass graft surgery patients. Med Care.

2000;38:207-217.
29

Chapter 3. Evidence-based Review Methodology

Definition and Scope

For this project the UCSF-Stanford Evidence-based Practice Center (EPC) defined a

patient safety practice as “a type of process or structure whose application reduces the

probability of adverse events resulting from exposure to the health care system across a range of

conditions or procedures.” Examples of practices that meet this definition include computerized

physician order entry (Chapter 6), thromboembolism prophylaxis in hospitalized patients

(Chapter 31), strategies to reduce falls among hospitalized elders (Chapter 26), and novel

education strategies such as the application of “crew resource management” to train operating

room staff (Chapter 44). By contrast, practices that are disease-specific and/or directed at the

underlying disease and its complications (eg, use of aspirin or beta-blockers to treat acute

myocardial infarction) rather than complications of medical care are not included as “patient

safety practices.” Further discussion of these issues can be found in Chapter 1.

In some cases, the distinction between patient safety and more general quality

improvement strategies is difficult to discern. Quality improvement practices may also qualify as

patient safety practices when the current level of quality is considered “unsafe,” but standards to

measure safety are often variable, difficult to quantify, and change over time. For example, what

constitutes an “adequate” or “safe” level of accuracy in electrocardiogram or radiograph

interpretation? Practices to improve performance to at least the “adequate” threshold may

reasonably be considered safety practices because they decrease the number of diagnostic errors

of omission. On the other hand, we considered practices whose main intent is to improve

performance above this threshold to be quality improvement practices. An example of the latter

might be the use of computer algorithms to improve the sensitivity of screening mammography.1

We generally included practices that involved acute hospital care or care at the interface

between inpatient and outpatient settings. This focus reflects the fact that the majority of the

safety literature relates to acute care and the belief that systems changes may be more effectively

achieved in the more controlled environment of the hospital. However, practices that might be

applicable in settings in addition to the hospital were not excluded from consideration. For

example, the Report includes practices for preventing decubitus ulcers (Chapter 27) that could be

applied in nursing homes as well as hospitals.

The EPC team received input regarding the scope of the Report from the Agency for

Healthcare Research and Quality (AHRQ), which commissioned the report. In addition, the EPC

team participated in the public meeting of the National Quality Forum (NQF) Safe Practices

Committee on January 26, 2001. The NQF was formed in 1999 by consumer, purchaser,

provider, health plan, and health service research organizations to create a national strategy for

quality improvement. Members of the Safe Practices Committee collaborated with the EPC team

to develop the scope of work that would eventually become this Report.

Organization by Domains

To facilitate identification and evaluation of potential patient safety practices, we divided

the content for the project into different domains. Some cover “content areas” (eg, adverse drug

events, nosocomial infections, and complications of surgery). Other domains involve

identification of practices within broad (primarily “non-medical”) disciplines likely to contain

promising approaches to improving patient safety (eg, information technology, human factors

research, organizational theory). The domains were derived from a general reading of the
30

literature and were meant to be as inclusive as possible. The list underwent review for

completeness by patient safety experts, clinician-researchers, AHRQ, and the NQF Safe

Practices Committee. For each domain we selected a team of author/collaborators with expertise

in the relevant subject matter and/or familiarity with the techniques of evidence-based review

and technology appraisal. The authors, all of whom are affiliated with major academic centers

around the United States, are listed on page 9-13.

Identification of Safety Practices for Evaluation

Search Strategy

The UCSF-Stanford Evidence-based Practice Center Coordinating Team (“The Editors”)

provided general instructions (Table 3.1) to the teams of authors regarding search strategies for

identifying safety practices for evaluation. As necessary, the Editors provided additional

guidance and supplementary searches of the literature.

Table 3.1. Search strategy recommended by coordinating team to

participating reviewers

a) Electronic bibliographic databases. All searches must include systematic

searches of MEDLINE and the Cochrane Library. For many topics it will

be necessary to include other databases such as the Cumulative Index to

Nursing & Allied Health (CINAHL), PsycLit (PsycINFO), the Institute for

Scientific Information’s Science Citation Index Expanded, Social Sciences

Citation Index, Arts & Humanities Citation Index, INSPEC (physics,

electronics and computing), and ABI/INFORM (business, management,

finance, and economics).

b) Hand-searches of bibliographies of retrieved articles and tables of

contents of key journals.

c) Grey literature. For many topics it will necessary to review the “grey

literature,” such as conference proceedings, institutional reports, doctoral

theses, and manufacturers’ reports.

d) Consultation with experts or workers in the field.

To meet the early dissemination date mandated by AHRQ, the Editors did not require

authors to search for non-English language articles or to use EMBASE. These were not

specifically excluded, however, and authoring teams could include non-English language articles

that addressed important aspects of a topic if they had translation services at their disposal. The

Editors did not make recommendations on limiting database searches based on publication date.

For this project it was particularly important to identify systematic reviews related to patient

safety topics. Published strategies for retrieving systematic reviews have used proprietary

MEDLINE interfaces (eg, OVID, SilverPlatter) that are not uniformly available. Moreover, the

performance characteristics of these search strategies is unknown.2,3 Therefore, these strategies

were not explicitly recommended. The Editors provided authors with a search algorithm

(available upon request) that uses PubMed, the freely available search interface from the

National Library of Medicine, designed to retrieve systematic reviews with high sensitivity

without overwhelming users with “false positive” hits.4
31

The Editors also performed independent searches of bibliographic databases and grey

literature for selected topics.5

 Concurrently, the EPC collaborated with NQF to solicit

information about evidence-based practices from NQF members, and consulted with the

project’s Advisory Panel (page 31), whose members provided additional literature to review.

Inclusion and Exclusion Criteria

The EPC established criteria for selecting which of the identified safety practices

warranted evaluation. The criteria address the applicability of the practice across a range of

conditions or procedures and the available evidence of the practices’ efficacy or effectiveness.

Table 3.2. Inclusion/Exclusion criteria for practices

Inclusion Criteria

1. The practice can be applied in the hospital setting or at the interface

between inpatient and outpatient settings AND can be applied to a broad

range of health care conditions or procedures.

2. Evidence for the safety practice includes at least one study with a Level 3

or higher study design AND a Level 2 outcome measure. For practices not

specifically related to diagnostic or therapeutic interventions, a Level 3

outcome measure is adequate. (See Table 3.3 for definition of “Levels”).

Exclusion Criterion

1. No study of the practice meets the methodologic criteria above.

Practices that have only been studied outside the hospital setting or in patients with

specific conditions or undergoing specific procedures were included if the authors and Editors

agreed that the practices could reasonably be applied in the hospital setting and across a range of

conditions or procedures. To increase the number of potentially promising safety practices

adapted from outside the field of medicine, we included evidence from studies that used less

rigorous measures of patient safety as long as the practices did not specifically relate to

diagnostic or therapeutic interventions. These criteria facilitated the inclusion of areas such as

teamwork training (Chapter 44) and methods to improve information transfer (Chapter 42).

Each practice’s level of evidence for efficacy or effectiveness was assessed in terms of

study design (Table 3.3) and study outcomes (Table 3.4). The Editors created the following

hierarchies by modifying existing frameworks for evaluating evidence6-8 and incorporating

recommendations from numerous other sources relevant to evidence synthesis.9-25
32

Table 3.3. Hierarchy of study designs*

Level 1. Randomized controlled trials – includes quasi-randomized processes

such as alternate allocation

Level 2. Non-randomized controlled trial – a prospective (pre-planned) study,

with predetermined eligibility criteria and outcome measures.

Level 3. Observational studies with controls – includes retrospective,

interrupted time series (a change in trend attributable to the

intervention), case-control studies, cohort studies with controls, and

health services research that includes adjustment for likely

confounding variables

Level 4. Observational studies without controls (eg, cohort studies without

controls and case series)

* Systematic reviews and meta-analyses were assigned to the highest level

study design included in the review, followed by an “A” (eg, a systematic

review that included at least one randomized controlled trial was designated

“Level 1A”)

Table 3.4. Hierarchy of outcome measures

Level 1. Clinical outcomes - morbidity, mortality, adverse events

Level 2. Surrogate outcomes - observed errors, intermediate outcomes (eg,

laboratory results) with well-established connections to the clinical

outcomes of interest (usually adverse events).

Level 3. Other measurable variables with an indirect or unestablished

connection to the target safety outcome (eg, pre-test/post-test after

an educational intervention, operator self-reports in different

experimental situations)

Level 4. No outcomes relevant to decreasing medical errors and/or adverse

events (eg, study with patient satisfaction as only measured

outcome; article describes an approach to detecting errors but reports

no measured outcomes)

Implicit in this hierarchy of outcome measures is that surrogate or intermediate outcomes

(Level 2) have an established relationship to the clinical outcomes (Level 1) of interest.26

Outcomes that are relevant to patient safety but have not been associated with morbidity or

mortality were classified as Level 3.

Exceptions to EPC Criteria

Some safety practices did not meet the EPC inclusion criteria because of the paucity of

evidence regarding efficacy or effectiveness, but were included in the Report because of their

face validity (ie, an informed reader might reasonably expect them to be evaluated; see also

Chapter 1). The reviews of these practices clearly identify the quality of evidence culled from

medical and non-medical fields.
33

Evaluation of Safety Practices

For each practice, authors were instructed to research the literature for information on:

• prevalence of the problem targeted by the practice

• severity of the problem targeted by the practice

• the current utilization of the practice

• evidence on efficacy and/or effectiveness of the practice

• the practice’s potential for harm

• data on cost if available

• implementation issues

These elements were incorporated into a template in an effort to create as much

uniformity across chapters as possible, especially given the widely disparate subject matter and

quality of evidence. Since the amount of material for each practice was expected to, and did,

vary substantially, the Editors provided general guidance on what was expected for each

element, with particular detail devoted to the protocol for searching and reporting evidence

related to efficacy and/or effectiveness of the practice.

The protocol outlined the search, the threshold for study inclusion, the elements to

abstract from studies, and guidance on reporting information from each study. Authors were

asked to review articles from their search to identify practices, and retain those with the better

study designs. More focused searches were performed depending on the topic. The threshold for

study inclusion related directly to study design. Authors were asked to use their judgment in

deciding whether the evidence was sufficient at a given level of study design or whether the

evidence from the next level needed to be reviewed. At a minimum, the Editors suggested that

there be at least 2 studies of adequate quality to justify excluding discussion of studies of lower

level designs. Thus inclusion of 2 adequate clinical trials (Level 1 design) were necessary in

order to exclude available evidence from prospective, non-randomized trials (Level 2) on the

same topic.

The Editors provided instructions for abstracting each article that met the inclusion

criteria based on study design. For each study, a required set of 10 abstraction elements (Table

3.5) was specified. Authors received a detailed explanation of each required abstraction element,

as well as complete abstraction examples for the 3 types of study design (Levels 1A, 1, and 3;

Level 2 was not included since the information collected was same as Level 1). Research teams

were encouraged to abstract any additional elements relevant to the specific subject area.
34

Table 3.5. Ten Required Abstraction Elements

1. Bibliographic information according to AMA Manual of Style: title, authors, date

of publication, source

2. Level of study design (eg, Level 1-3 for studies providing information for

effectiveness; Level 4 if needed for relevant additional information) with

descriptive material as follows:

Descriptors

For Level 1 Systematic Reviews Only

(a) Identifiable description of methods indicating sources and methods of

searching for articles.

(b) Stated inclusion and exclusion criteria for articles: yes/no.

(c) Scope of literature included in study.

For Level 1 or 2 Study Designs (Not Systematic Reviews)

(a) Blinding: blinded, blinded (unclear), or unblinded

(b) Describe comparability of groups at baseline – ie, was distribution of potential

confounders at baseline equal? If no, which confounders were not equal?

(c) Loss to follow-up overall: percent of total study population lost to follow-up.

For Level 3 Study Design (Not Systematic Reviews)

(a) Description of study design (eg, case-control, interrupted time series).

(b) Describe comparability of groups at baseline – ie, was distribution of potential

confounders at baseline equal? If no, which confounders were not equal?

(c) Analysis includes adjustment for potential confounders: yes/no. If yes,

adjusted for what confounders?

3. Description of intervention (as specific as possible)

4. Description of study population(s) and setting(s)

5. Level of relevant outcome measure(s) (eg, Levels 1-4)

6. Description of relevant outcome measure(s)

7. Main Results: effect size with confidence intervals

8. Information on unintended adverse (or beneficial) effects of practice

9. Information on cost of practice

10. Information on implementation of practice (information that might be of use in

whether to and/or how to implement the practice – eg, known barriers to

implementation)

We present the salient elements of each included study (eg, study design,

population/setting, intervention details, results) in text or tabular form. In addition, we asked

authors to highlight weaknesses and biases of studies where the interpretation of the results

might be substantially affected. Authors were not asked to formally synthesize or combine (eg,

perform a meta-analysis) the evidence across studies for the Report.
35

Review Process

Authors submitted work to the Editors in 2 phases. In the first phase (“Identification of

Safety Practices for Evaluation”), which was submitted approximately 6 weeks after authors

were commissioned, authoring teams provided their search strategies, citations, and a

preliminary list of patient safety practices to be reviewed. In the subsequent phase (“Evaluation

of Safety Practices”), due approximately 12 weeks after commissioning, authors first submitted a

draft chapter for each topic, completed abstraction forms, and—after iterative reviews and

revisions—a final chapter.

Identification of Safety Practices for Evaluation

The Editors and the Advisory Panel reviewed the list of domains and practices to identify

gaps in coverage. In addition, the Editors reviewed final author-submitted lists of excluded

practices along with justifications for exclusion (eg, insufficient research design, insufficient

outcomes, practice is unique to a single disease process). When there were differences in opinion

as to whether a practice actually met the inclusion or exclusion criteria, the Editors made a final

disposition after consulting with the author(s). The final practice list, in the form of a Table of

Contents for the Report, was circulated to AHRQ and the NQF Safe Practices Committee for

comment.

Evaluation of Safety Practices

Chapters were reviewed by the editorial team (The EPC Coordinating Team Editors and

our Managing Editor) and queries were relayed to the authors, often requesting further

refinement of the analysis or expansion of the results and conclusions. After all chapters were

completed, the entire Report was edited to eliminate redundant material and ensure that the focus

remained on the evidence regarding safety practices. Near the end of the review process,

chapters were distributed to the Advisory Panel for comments, many of which were

incorporated. Once the content was finalized, the Editors analyzed and ranked the practices using

a methodology described in Chapter 56. The results of these summaries and rankings are

presented in Part V of the Report.
36

References

1. Thurfjell E, Thurfjell MG, Egge E, Bjurstam N. Sensitivity and specificity of computerassisted breast cancer detection in mammography screening. Acta Radiol. 1998;39:384-

388.

2. Hunt DL, McKibbon KA. Locating and appraising systematic reviews Ann Intern Med.

1997;126:532-538.

3. Glanville J, Lefebvre C. Identifying systematic reviews: key resources. ACP J Club.

2000;132:A11-A12.

4. Shojania KG, Bero L. Taking advantage of the explosion of systematic reviews: an

efficient MEDLINE search strategy. Eff Clin Pract. 2001;4: in press.

5. McAuley L, Pham B, Tugwell P, Moher D. Does the inclusion of grey literature influence

estimates of intervention effectiveness reported in meta-analyses? Lancet. 2000;356:1228-

1231.

6. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Current

methods of the U.S. Preventive Services Task Force. A review of the process. Am J Prev

Med. 2001;20:21-35.

7. Guyatt G, Schunemann H, Cook D, Jaeschke R, Pauker S, Bucher H. Grades of

recommendation for antithrombotic agents. Chest.2001;119:3S-7S.

8. Muir Gray JA, Haynes RB, Sackett DL, Cook DJ, Guyatt GH. Transferring evidence from

research into practice: 3. Developing evidence-based clinical policy. ACP J Club.

1997;126:A14-A16.

9. Guyatt GH, Tugwell PX, Feeny DH, Drummond MF, Haynes RB. The role of before-after

studies of therapeutic impact in the evaluation of diagnostic technologies. J Chronic Dis.

1986;39:295-304.

10. Davis CE. Generalizing from clinical trials. Control Clin Trials. 1994;15:11-4.

11. Bailey KR. Generalizing the results of randomized clinical trials. Control Clin Trials.

1994;15:15-23.

12. Oxman AD, Cook DJ, Guyatt GH. Users' guides to the medical literature. VI. How to use

an overview. Evidence-Based Medicine Working Group. JAMA. 1994;272:1367-1371.

13. Levine M, Walter S, Lee H, Haines T, Holbrook A, Moyer V. Users' guides to the medical

literature. IV. How to use an article about harm. Evidence-Based Medicine Working

Group. JAMA. 1994;271:1615-1619.

14. Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ, Cook RJ. Users' guides to the

medical literature. IX. A method for grading health care recommendations. EvidenceBased Medicine Working Group. JAMA. 1995;274:1800-1804.

15. Cook DJ, Guyatt GH, Laupacis A, Sackett DL, Goldberg RJ. Clinical recommendations

using levels of evidence for antithrombotic agents. Chest. 1995;108:227S-230S.

16. Naylor CD, Guyatt GH. Users' guides to the medical literature. X. How to use an article

reporting variations in the outcomes of health services. The Evidence-Based Medicine

Working Group. JAMA. 1996;275:554-558.

17. Moher D, Jadad AR, Tugwell P. Assessing the quality of randomized controlled trials.

Current issues and future directions. Int J Technol Assess Health Care. 1996;12:195-208.

18. Mulrow C, Langhorne P, Grimshaw J. Integrating heterogeneous pieces of evidence in

systematic reviews. Ann Intern Med. 1997;127:989-995.

19. Jadad AR, Cook DJ, Browman GP. A guide to interpreting discordant systematic reviews.

CMAJ. 1997;156:1411-1416.
37

20. Juni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials

for meta-analysis. JAMA. 1999;282:1054-1060.

21. McKee M, Britton A, Black N, McPherson K, Sanderson C, Bain C. Methods in health

services research. Interpreting the evidence: choosing between randomised and nonrandomised studies. BMJ. 1999;319:312-315.

22. Bucher HC, Guyatt GH, Cook DJ, Holbrook A, McAlister FA. Users' guides to the medical

literature: XIX. Applying clinical trial results. A. How to use an article measuring the

effect of an intervention on surrogate end points. Evidence-Based Medicine Working

Group. JAMA. 1999;282:771-778.

23. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and

the hierarchy of research designs. N Engl J Med. 2000;342:1887-1892.

24. Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled

trials. N Engl J Med. 2000;342:1878-1886.

25. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis

of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of

Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008-2012.

26. Gotzsche PC, Liberati A, Torri V, Rossetti L. Beware of surrogate outcome measures. Int J

Technol Assess Health Care. 1996;12:238-246.
38
39

PART II. REPORTING AND RESPONDING TO PATIENT SAFETY PROBLEMS

Chapter 4. Incident Reporting

Chapter 5. Root Cause Analysis
40
41

Chapter 4. Incident Reporting

Heidi Wald, MD

University of Pennsylvania School of Medicine

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

Background

Errors in medical care are discovered through a variety of mechanisms. Historically,

medical errors were revealed retrospectively through morbidity and mortality committees and

malpractice claims data. Prominent studies of medical error have used retrospective chart review

to quantify adverse event rates.1,2 While collection of data in this manner yields important

epidemiologic information, it is costly and provides little insight into potential error reduction

strategies. Moreover, chart review only detects documented adverse events and often does not

capture information regarding their causes. Important errors that produce no injury may go

completely undetected by this method.3-6

Computerized surveillance may also play a role in uncovering certain types of errors. For

instance, medication errors may be discovered through a search for naloxone orders for

hospitalized patients, as they presumably reflect the need to reverse overdose of prescribed

narcotics.7,8 Several studies have demonstrated success with computerized identification of

adverse drug events.9-11

Complex, high-risk industries outside of health care, including aviation, nuclear power,

petrochemical processing, steel production, and military operations, have successfully developed

incident reporting systems for serious accidents and important “near misses.”

6

 Incident reporting

systems cannot provide accurate epidemiologic data, as the reported incidents likely

underestimate the numerator, and the denominator (all opportunities for incidents) remains

unknown.

Given the limited availability of sophisticated clinical computer systems and the

tremendous resources required to conduct comprehensive chart reviews, incident reporting

systems remain an important and relatively inexpensive means of capturing data on errors and

adverse events in medicine. Few rigorous studies have analyzed the benefits of incident

reporting. This chapter reviews only the literature evaluating the various systems and techniques

for collecting error data in this manner, rather than the benefit of the practice itself. This decision

reflects our acknowledgment that incident reporting has clearly played a beneficial role in other

high-risk industries.6

 The decision also stems from our recognition that a measurable impact of

incident reporting on clinical outcomes is unlikely because there is no standard practice by which

institutions handle these reports.

Practice Description

Flanagan first described the critical incident technique in 1954 to examine military

aircraft training accidents.12 Critical incident reporting involves the identification of preventable

incidents (ie, occurrences that could have led, or did lead, to an undesirable outcome13) reported

by personnel directly involved in the process in question at the time of discovery of the event.

The goal of critical incident monitoring is not to gather epidemiologic data per se, but rather to

gather qualitative data. Nonetheless, if a pattern of errors seems to emerge, prospective studies

can be undertaken to test epidemiologic hypotheses.14
42

Incident reports may target events in any or all of 3 basic categories: adverse events, “no

harm events,” and “near misses.” For example, anaphylaxis to penicillin clearly represents an

adverse event. Intercepting the medication order prior to administration would constitute a near

miss. By contrast, if a patient with a documented history of anaphylaxis to penicillin received a

penicillin-like antibiotic (eg, a cephalosporin) but happened not to experience an allergic

reaction, it would constitute a no harm event, not a near miss. In other words, when an error does

not result in an adverse event for a patient, because the error was “caught,” it is a near miss; if

the absence of injury is owed to chance it is a no harm event. Broadening the targets of incident

reporting to include no harm events and near misses offers several advantages. These events

occur 3 to 300 times more often than adverse events,5,6 they are less likely to provoke guilt or

other psychological barriers to reporting,6

 and they involve little medico-legal risk.14 In addition,

hindsight bias15 is less likely to affect investigations of no harm events and near misses.6,14

Barach and Small describe the characteristics of incident reporting systems in nonmedical industries.6

 Established systems share the following characteristics:

• they focus on near misses

• they provide incentives for voluntary reporting;

• they ensure confidentiality; and

• they emphasize systems approaches to error analysis.

The majority of these systems were mandated by Federal regulation, and provide for

voluntary reporting. All of the systems encourage narrative description of the event. Reporting is

promoted by providing incentives including:

• immunity;

• confidentiality;

• outsourcing of report collation;

• rapid feedback to all involved and interested parties; and

• sustained leadership support.6

Incident reporting in medicine takes many forms. Since 1975, the US Food and Drug

Administration (FDA) has mandated reporting of major blood transfusion reactions, focusing on

preventable deaths and serious injuries.16 Although the critical incident technique found some

early applications in medicine,17,18 its current use is largely attributable to Cooper’s introduction

of incident reporting to anesthesia in 1978,19 conducting retrospective interviews with

anesthesiologists about preventable incidents or errors that occurred while patients were under

their care. Recently, near miss and adverse event reporting systems have proliferated in single

institution settings (such as in intensive care units (ICUs)20,21), regional settings (such as the New

York State transfusion system22), and for national surveillance (eg, the National Nosocomial

Infections Surveillance System administered by the Federal Centers for Disease Control and

Prevention.)23

All of the above examples focus on types of events (transfusion events or nosocomial

infections) or areas of practice (ICUs). Incident reporting in hospitals cuts a wider swath,

capturing errors and departures from expected procedures or outcomes (Table 4.1). However,

because risk management departments tend to oversee incident reporting systems in some

capacity, these systems more often focus on incident outcomes, not categories. Few data describe

the operation of these institution-specific systems, but underreporting appears endemic.24
43

In 1995, hospital-based surveillance was mandated by the Joint Commission on the

Accreditation of Healthcare Organizations (JCAHO)26 because of a perception that incidents

resulting in harm were occurring frequently.28 JCAHO employs the term sentinel event in lieu of

critical incident, and defines it as follows:

An unexpected occurrence involving death or serious physical or psychological

injury, or the risk thereof. Serious injury specifically includes loss of limb or

function. The phrase “or the risk thereof” includes any process variation for

which a recurrence would carry a significant chance of a serious adverse

outcome.26

As one component of its Sentinel Event Policy, JCAHO created a Sentinel Event

Database. The JCAHO database accepts voluntary reports of sentinel events from member

institutions, patients and families, and the press.26 The particulars of the reporting process are left

to the member health care organizations. JCAHO also mandates that accredited hospitals

perform root cause analysis (see Chapter 5) of important sentinel events. Data on sentinel events

are collated, analyzed, and shared through a website,29 an online publication,30 and its newsletter

Sentinel Event Perspectives.

31

Another example of a national incident reporting system is the Australian Incident

Monitoring Study (AIMS), under the auspices of the Australian Patient Safety Foundation.13

Investigators created an anonymous and voluntary near miss and adverse event reporting system

for anesthetists in Australia. Ninety participating hospitals and practices named on-site

coordinators. The AIMS group developed a form that was distributed to participants. The form

contained instructions, definitions, space for narrative of the event, and structured sections to

record the anesthesia and procedure, demographics about the patient and anesthetist, and what,

when, why, where, and how the event occurred. The results of the first 2000 reports were

published together, following a special symposium.32

The experiences of the JCAHO Sentinel Event Database and the Australian Incident

Monitoring Study are explored further below.

Prevalence and Severity of the Target Safety Problem

The true prevalence of events appropriate for incident reporting is impossible to estimate with

any accuracy, as it includes actual adverse events as well as near misses and no harm events. The

Aviation Safety Reporting System (ASRS), a national reporting system for near misses in the

airline industry,33,34 currently processes approximately 30,000 reports annually,35 exceeding

by many orders of magnitude the total number of airline accidents each year.34 The number of

reports submitted to a comparable system in health care would presumably number in the

millions if all adverse events, no harm events, and near misses were captured.

By contrast, over 6 years of operation, the JCAHO Sentinel Event Database has captured

only 1152 events, 62% of which occurred in general hospitals. Two-thirds of the events were

self-reported by institutions, with the remainder coming from patient complaints, media stories

and other sources.29 These statistics are clearly affected by underreporting and consist primarily

of serious adverse events (76% of events reported resulted in patient deaths), not near misses. As

discussed in the chapter on wrong-site surgeries (Subchapter 43.2), comparing JCAHO reports

with data from the mandatory incident reporting system maintained by the New York State

Department of Health36 suggests that the JCAHO statistics underestimate the true incidence of

target events by at least a factor of 20.
44

Opportunities for Impact

Most hospitals’ incident reporting systems fail to capture the majority of errors and near

misses.24 Studies of medical services suggest that only 1.5% of all adverse events result in an

incident report37 and only 6% of adverse drug events are identified through traditional incident

reporting or a telephone hotline.24 The American College of Surgeons estimates that incident

reports generally capture only 5-30% of adverse events.38 A study of a general surgery service

showed that only 20% of complications on a surgical service ever resulted in discussion at

Morbidity and Mortality rounds.39 Given the endemic underreporting revealed in the literature,

modifications to the configuration and operation of the typical hospital reporting system could

yield higher capture rates of relevant clinical data.

Study Designs

We analyzed 5 studies that evaluated different methods of critical incident reporting.

Two studies prospectively investigated incident reporting compared with observational data

collection24,39 and one utilized retrospective chart review.37 Two additional studies looked at

enhanced incident reporting by active solicitation of physician input compared with background

hospital quality assurance (QA) measures.40,41 In addition, we reviewed JCAHO’s report of its

Sentinel Event Database, and the Australian Incident Monitoring Study, both because of the

large sizes and the high profiles of the studies.13,26 Additional reports of critical incident

reporting systems in the medical literature consist primarily of uncontrolled observational

trials42-44 that are not reviewed in this chapter.

Study Outcomes

In general, published studies of incident reporting do not seek to establish the benefit of

incident reporting as a patient safety practice. Their principal goal is to determine if incident

reporting, as it is practiced, captures the relevant events.40 In fact, no studies have established the

value of incident reporting on patient safety outcomes.

The large JCAHO and Australian databases provide data about reporting rates, and an

array of quantitative and qualitative information about the reported incidents, including the

identity of the reporter, time of report, severity and type of error.13,26 Clearly these do not

represent clinical outcomes, but they may be reasonable surrogates for the organizational focus

on patient safety. For instance, increased incident reporting rates may not be indicative of an

unsafe organization,45 but may reflect a shift in organizational culture to increased acceptance of

quality improvement and other organizational changes.3,5

None of the studies reviewed captured outcomes such as morbidity or error rates. The

AIMS group published an entire symposium which reported the quantitative and qualitative data

regarding 2000 critical incidents in anesthesia.13 However, only a small portion of these

incidents were prospectively evaluated.14 None of the studies reviewed for this chapter

performed formal root cause analyses on reported errors (Chapter 5).

Evidence for Effectiveness of the Practice

As described above, 6 years of JCAHO sentinel event data have captured merely 1152

events, none of which include near misses.29 Despite collecting what is likely to represent only a

fraction of the target events, JCAHO has compiled the events, reviewed the root cause analyses

and provided recommendations for procedures to improve patient safety for events ranging from

wrong-site surgeries to infusion pump-related adverse events (Table 4.2). This information may
45

prove to be particularly useful in the case of rare events such as wrong-site surgery, where

national collection of incidents can yield a more statistically useful sample size.

The first 2000 incident reports to AIMS from 90 member institutions were published in

1993.13 In contrast to the JCAHO data, all events were self-reported by anesthetists and only 2%

of events reported resulted in patient deaths. A full 44% of events had negligible effect on

patient outcome. Ninety percent of reports had identified systems failures, and 79% had

identified human failures. The AIMS data were similar to those of Cooper19 in terms of percent

of incidents with reported human failures, timing of events with regard to phase of anesthesia,

and type of events (breathing circuit misconnections were between 2% and 3% in both

studies).13,19 The AIMS data are also similar to American “closed-claims” data in terms of

pattern, nature and proportion of the total number of reports for several types of adverse events,13

which lends further credibility to the reports.

The AIMS data, although also likely to be affected by underreporting because of its

voluntary nature, clearly captures a higher proportion of critical incidents than the JCAHO

Sentinel Event Database. Despite coming from only 90 participating sites, AIMS received more

reports over a similar time frame than the JCAHO did from the several thousand accredited

United States hospitals. This disparity may be explained by the fact that AIMS institutions were

self-selected, and that the culture of anesthesia is more attuned to patient safety concerns.47

The poor capture rate of incident reporting systems in American hospitals has not gone

unnoticed. Cullen et al24 prospectively investigated usual hospital incident reporting compared to

observational data collection for adverse drug events (ADE logs, daily solicitation from hospital

personnel, and chart review) in 5 patient care units of a tertiary care hospital. Only 6% of ADEs

were identified and only 8% of serious ADEs were reported. These findings are similar to those

in the pharmacy literature,48,49 and are attributed to cultural and environmental factors. A similar

study on a general surgical service found that 40% of patients suffered complications.39 While

chart documentation was excellent (94%), only 20% of complications were discussed at

Morbidity and Mortality rounds.

Active solicitation of physician reporting has been suggested as a way to improve

adverse event and near miss detection rates. Weingart et al41 employed direct physician

interviews supplemented by email reminders to increase detection of adverse events in a tertiary

care hospital. The physicians reported an entirely unique set of adverse events compared with

those captured by the hospital incident reporting system. Of 168 events, only one was reported

by both methods. O’Neil et al37 used e-mail to elicit adverse events from housestaff and

compared these with those found on retrospective chart review. Of 174 events identified, 41

were detected by both methods. The house officers appeared to capture preventable adverse

events at a higher rate (62.5% v. 32%, p=0.003). In addition, the hospital’s risk management

system detected only 4 of 174 adverse events. Welsh et al40 employed prompting of house

officers at morning report to augment hospital incident reporting systems. There was overlap in

reporting in only 2.6% of 341 adverse events that occurred during the study. In addition,

although the number of events house officers reported increased with daily prompting, the

quantity rapidly decreased when prompting ceased. In summary, there is evidence that active

solicitation of critical incident reports by physicians can augment existing databases, identifying

incidents not detected through other means, although the response may not be durable.37,40,41

Potential for Harm

Users may view reporting systems with skepticism, particularly the system’s ability to

maintain confidentiality and shield participants from legal exposure.28 In many states, critical
46

incident reporting and analysis count as peer review activities and are protected from legal

discovery.28,50 However, other states offer little or no protection, and reporting events to external

agencies (eg, to JCAHO) may obliterate the few protections that do exist. In recognition of this

problem, JCAHO’s Terms of Agreement with hospitals now includes a provision identifying

JCAHO as a participant in each hospital’s quality improvement process.28

Costs and Implementation

Few estimates of costs have been reported in the literature. In general, authors remarked

that incident reporting was far less expensive than retrospective review. One single center study

estimated that physician reporting was less costly ($15,000) than retrospective record review

($54,000) over a 4-month period.37 A survey of administrators of reporting systems from nonmedical industries reported a consensus that costs were far offset by the potential benefits.6

Comment

The wide variation in reporting of incidents may have more to do with reporting

incentives and local culture than with the quality of medicine practiced there.24 When institutions

prioritize incident reporting among medical staff and trainees, however, the incident reporting

systems seem to capture a distinct set of events from those captured by chart review and

traditional risk management40,41 and events captured in this manner may be more preventable.37

The addition of anonymous or non-punitive systems is likely to increase the rates of

incident reporting and detection.51 Other investigators have also noted increases in reporting

when new systems are implemented and a culture conducive to reporting is maintained.40,52

Several studies suggest that direct solicitation of physicians results in reports that are more likely

to be distinct, preventable, and more severe than those obtained by other means.8,37,41

The nature of incident reporting, replete with hindsight bias, lost information, and lost

contextual clues makes it unlikely that robust data will ever link it directly with improved

outcomes. Nonetheless, incident reporting appears to be growing in importance in medicine. The

Institute of Medicine report, To Err is Human,

53 has prompted calls for mandatory reporting of

medical errors to continue in the United States.54-57 England’s National Health Service plans to

launch a national incident reporting system as well, which has raised concerns similar to those

voiced in the American medical community.58 While the literature to date does not permit an

evidence-based resolution of the debate over mandatory versus voluntary incident reporting, it is

clear that incident reporting represents just one of several potential sources of information about

patient safety and that these sources should be regarded as complementary. In other industries

incident reporting has succeeded when it is mandated by regulatory agencies or is anonymous

and voluntary on the part of reporters, and when it provides incentives and feedback to

reporters.6

 The ability of health care organizations to replicate the successes of other industries in

their use of incident reporting systems6

 will undoubtedly depend in large part on the uses to

which they put these data. Specifically, success or failure may depend on whether health care

organizations use the data to fuel institutional quality improvement rather than to generate

individual performance evaluations.
47

Table 4.1. Examples of events reported to hospital incident reporting systems25-27

Adverse Outcomes Procedural Breakdowns Catastrophic Events

• Unexpected death or

disability

• Inpatient falls or

“mishaps”

• Institutionally-acquired

burns

• Institutionally-acquired

pressure sores

• Errors or unexpected

complications related to the

administration of drugs or

transfusion

• Discharges against medical

advice (“AMA”)

• Significant delays in

diagnosis or diagnostic

testing

• Breach of confidentiality

• Performance of a procedure on the

wrong body part (“wrong-site

surgery”)

• Performance of a procedure on the

wrong patient

• Infant abduction or discharge to

wrong family

• Rape of a hospitalized patient

• Suicide of a hospitalized patient

Table 4.2. Sentinel event alerts published by JCAHO following analysis of incident

reports46

• Medication Error Prevention – Potassium Chloride

• Lessons Learned: Wrong Site Surgery

• Inpatient Suicides: Recommendations for Prevention

• Preventing Restraint Deaths

• Infant Abductions: Preventing Future Occurrences

• High-Alert Medications and Patient Safety

• Operative and Postoperative Complications: Lessons for the Future

• Fatal Falls: Lessons for the Future

• Infusion Pumps: Preventing Future Adverse Events

• Lessons Learned: Fires in the Home Care Setting

• Kernicterus Threatens Healthy Newborns
48

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33. Billings C, Reynard W. Human factors in aircraft incidents: results of a 7-year study. Aviat

Space Environ Med. 1984;55:960-965.

34. National Aeronautics & Space Agency (NASA). Aviation Safety Reporting System.

Available at: http://www-afo.arc.nasa.gov/ASRS/ASRS.html. Accessed March 14, 2000.

35. Leape L. Reporting of medical errors: time for a reality check. Qual Health Care.

2000;9:144-145.

36. New York State Department of Health. NYPORTS - The New York Patient Occurrence

and Tracking System. Available at:

http://www.health.state.ny.us/nysdoh/commish/2001/nyports/nyports.htm. Accessed May

31, 2001.

37. O'Neil A, Petersen L, Cook E, Bates D, Lee T, Brennan T. Physician reporting compared

with medical-record review to identify adverse medical events. Ann Intern Med.

1993;119:370-376.

38. Data sources and coordination. In: Surgeons ACo, editor. Patient safety manual. Rockville,

MD: Bader & Associates, Inc. 1985.

39. Wanzel K, Jamieson C, Bohnen J. Complications on a general surgery service: incidence

and reporting. CJS. 2000;43:113-117.

40. Welsh C, Pedot R, Anderson R. Use of morning report to enhance adverse event detection.

J Gen Intern Med. 1996;11:454-460.
50

41. Weingart SN, Ship AN, Aronson MD. Confidential clinician-reported surveillance of

adverse events among medical inpatients. J Gen Intern Med. 2000;15:470-477.

42. Frey B, Kehrer B, Losa M, Braun H, Berweger L, Micallef J, et al. Comprehensive critical

incident monitoring in a neonatal-pediatric intensive care unit: experience with the system

approach. Intensive Care Med. 2000;26:69-74.

43. Findlay G, Spittal M, Radcliffe J. The recognition of critical incidents: quantification of

monitor effectiveness. Anaesthesia. 1998;53:589-603.

44. Flaatten H, Hevroy O. Errors in the intensive care unit (ICU). Act Anaesthesiol Scand.

1999;43:614-617.

45. Connolly C. Reducing error, improving safety: relation between reported mishaps and

safety is unclear. BMJ. 2000;321:505.

46. The Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Alert.

Available at: http://www.JCAHO.org/edu_pub/sealert/se_alert.html. Accessed May 31,

2001.

47. Gaba D. Anaesthesiology as a model for patient safety in health care. BMJ. 2000;320.

48. Shannon R, De Muth J. Comparison of medication error detection methods in the long term

care facility. Consulting Pharmacy. 1987;2:148-151.

49. Allan E, Barker K. Fundamentals of medication error research. Am J Hosp Pharm.

1990;47:555-571.

50. Rex J, Turnbull J, Allen S, Vande Voorde K, Luther K. Systematic root cause analysis of

adverse drug events in a tertiary referral hospital. Jt Comm J Qual Improv. 2000;26:563-

575.

51. Kaplan H, Battles J, Van Der Schaaf T, Shea C, Mercer S. Identification and classification

of the causes of events in transfusion medicine. Transfusion. 1998;38:1071-1081.

52. Hartwig S, Denger S, Schneider P. Severity-indexed, incident report-based medication

error-reporting program. Am J Hosp Pharm. 1991;48:2611-2616.

53. Kohn L, Corrigan J, Donaldson M, editors. To Err Is Human: Building a Safer Health

System. Washington, DC: Committee on Quality of Health Care in America, Institute of

Medicine. National Academy Press. 2000.

54. Pear R. U.S. health officials reject plan to report medical mistakes. New York Times Jan 24

2000: A14(N), A14(L).

55. Prager LO. Mandatory reports cloud error plan: supporters are concerned that the merits of

a plan to reduce medical errors by 50% are being obscured by debate over its most

controversial component. American Medical News March 13 2000:1,66-67.

56. Murray S. Clinton to call on all states to adopt systems for reporting medical errors. Wall

Street Journal Feb 22 2000:A28(W), A6(E).

57. Kaufman M. Clinton Seeks Medical Error Reports; Proposal to Reduce Mistakes Includes

Mandatory Disclosure, Lawsuit Shield. Washington Post Feb 22 2000:A02.

58. Mayor S. English NHS to set up new reporting system for errors. BMJ. 2000;320:1689.
51

Chapter 5. Root Cause Analysis

Heidi Wald, MD

University of Pennsylvania School of Medicine

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

Background

Historically, medicine has relied heavily on quantitative approaches for quality

improvement and error reduction. For instance, the US Food and Drug Administration (FDA)

has collected data on major transfusion errors since the mid-1970s.1,2 Using the statistical power

of these nationwide data, the most common types of errors have been periodically reviewed and

systems improvements recommended.3

These epidemiologic techniques are suited to complications that occur with reasonable

frequency, but not for rare (but nonetheless important) errors. Outside of medicine, high-risk

industries have developed techniques to address major accidents. Clearly the nuclear power

industry cannot wait for several Three Mile Island-type events to occur in order to conduct valid

analyses to determine the likely causes.

A retrospective approach to error analysis, called root cause analysis (RCA), is widely

applied to investigate major industrial accidents.4

 RCA has its foundations in industrial

psychology and human factors engineering. Many experts have championed it for the

investigation of sentinel events in medicine.5-7 In 1997, the Joint Commission on the

Accreditation of Healthcare Organizations (JCAHO) mandated the use of RCA in the

investigation of sentinel events in accredited hospitals.8

The most commonly cited taxonomy of human error in the medical literature is based on

the work of James Reason.4,9,10 Reason describes 2 major categories of error: active error, which

generally occurs at the point of human interface with a complex system, and latent error, which

represents failures of system design. RCA is generally employed to uncover latent errors

underlying a sentinel event.6,7

RCA provides a structured and process-focused framework with which to approach

sentinel event analysis. Its cardinal tenet is to avoid the pervasive and counterproductive culture

of individual blame.11,12 Systems and organizational issues can be identified and addressed, and

active errors are acknowledged.6

 Systematic application of RCA may uncover common root

causes that link a disparate collection of accidents (ie, a variety of serious adverse events

occurring at shift change). Careful analysis may suggest system changes designed to prevent

future incidents.13

Despite these intriguing qualities, RCA has significant methodologic limitations. RCAs

are in essence uncontrolled case studies. As the occurrence of accidents is highly unpredictable,

it is impossible to know if the root cause established by the analysis is the cause of the

accident.14 In addition, RCAs may be tainted by hindsight bias.4,15,16 Other biases stem from how

deeply the causes are probed and influenced by the prevailing concerns of the day.16,17 The fact

that technological failures (device malfunction), which previously represented the focus of most

accident analyses, have been supplanted by staffing issues, management failures, and

information systems problems may be an example of the latter bias.17 Finally, RCAs are timeconsuming and labor intensive.
52

Despite legitimate concerns about the place of RCA in medical error reduction, the

JCAHO mandate ensures that RCA will be widely used to analyze sentinel events.8

 Qualitative

methods such as RCA should be used to supplement quantitative methods, to generate new

hypotheses, and to examine events not amenable to quantitative methods (for example, those that

occur rarely).18 As such, its credibility as a research tool should be judged by the standards

appropriate for qualitative research, not quantitative.19,20 Yet, the outcomes and costs associated

with RCA are largely unreported. This chapter reviews the small body of published literature

regarding the use of RCA in the investigation of medical errors.

Practice Description

To be credible, RCA requires rigorous application of established qualitative techniques.

Once a sentinel event has been identified for analysis (eg, a major chemotherapy dosing error, a

case of wrong-site surgery, or major ABO incompatible transfusion reaction), a multidisciplinary

team is assembled to direct the investigation. The members of this team should be trained in the

techniques and goals of RCA, as the tendency to revert to personal biases is strong.13,14 Multiple

investigators allow triangulation or corroboration of major findings and increase the validity of

the final results.19 Based on the concepts of active and latent error described above, accident

analysis is generally broken down into the following steps6,7:

1. Data collection: establishment of what happened through structured

interviews, document review, and/or field observation. These data are used to

generate a sequence or timeline of events preceeding and following the event;

2. Data analysis: an iterative process to examine the sequence of events

generated above with the goals of determining the common underlying

factors:

(i) Establishment of how the event happened by identification of active

failures in the sequence;

(ii) Establishment of why the event happened through identification of latent

failures in the sequence which are generalizable.

In order to ensure consideration of all potential root causes of error, one popular

conceptual framework for contributing factors has been proposed based on work by Reason.7

Several other frameworks also exist.21,22 The categories of factors influencing clinical practice

include institutional/regulatory, organizational/management, work environment, team factors,

staff factors, task factors, and patient characteristics. Each category can be expanded to provide

more detail. A credible RCA considers root causes in all categories before rejecting a factor or

category of factors as non-contributory. A standardized template in the form of a tree (or

“Ishikawa”) may help direct the process of identifying contributing factors, with such factors

leading to the event grouped (on tree “roots”) by category. Category labels may vary depending

on the setting.23

At the conclusion of the RCA, the team summarizes the underlying causes and their

relative contributions, and begins to identify administrative and systems problems that might be

candidates for redesign.6

Prevalence and Severity of the Target Safety Problem

JCAHO’s 6-year-old sentinel event database of voluntarily reported incidents (see

Chapter 4) has captured a mere 1152 events, of which 62% occurred in general hospitals. Twothirds of the events were self-reported by institutions, with the remainder coming from patient
53

complaints, media stories and other sources.24 These statistics are clearly affected by

underreporting and consist primarily of serious adverse events (76% of events reported resulted

in patient deaths), not near misses. The number of sentinel events appropriate for RCA is likely

to be orders of magnitude greater.

The selection of events for RCA may be crucial to its successful implementation on a

regular basis. Clearly, it cannot be performed for every medical error. JCAHO provides guidance

for hospitals about which events are considered “sentinel,”

8

 but the decision to conduct RCA is

at the discretion of the leadership of the organization.12

If the number of events is large and homogeneous, many events can be excluded from

analysis. In a transfusion medicine reporting system, all events were screened after initial report

and entered in the database, but those not considered sufficiently unique did not undergo RCA.25

Opportunities for Impact

While routine RCA of sentinel events is mandated, the degree to which hospitals carry

out credible RCAs is unknown. Given the numerous demands on hospital administrators and

clinical staff, it is likely that many hospitals fail to give this process a high profile, assigning the

task to a few personnel with minimal training in RCA rather than involving trained leaders from

all relevant departments. The degree of underreporting to JCAHO suggests that many hospitals

are wary of probationary status and the legal implications of disclosure of sentinel events and the

results of RCAs.12,26

Study Designs

As RCA is a qualitative technique, most reports in the literature are case studies or case

series of its application in medicine.6,27-30 There is little published literature that systematically

evaluates the impact of formal RCA on error rates. The most rigorous study comes from a

tertiary referral hospital in Texas that systematically applied RCA to all serious adverse drug

events (ADEs) considered preventable. The time series contained background data during the

initial implementation period of 12 months and a 17-month follow-up phase.13

Study Outcomes

Published reports of the application of RCA in medicine generally present incident

reporting rates, categories of active errors determined by the RCA, categories of root causes

(latent errors) of the events, and suggested systems improvements. While these do not represent

clinical outcomes, they are reasonable surrogates for evaluation. For instance, increased incident

reporting rates may reflect an institution’s shift toward increased acceptance of quality

improvement and organizational change.5,21
54

Evidence for Effectiveness of the Practice

The Texas study revealed a 45% decrease in the rate of voluntarily reported serious

ADEs between the study and follow-up periods (7.2 per 100,000 to 4.0 per 100,000 patient-days,

p<0.001).13 Although there were no fatal ADEs in the follow-up period, the small number of

mortalities in the baseline period resulted in extremely wide confidence intervals, so that

comparing the mortality rates serves little purpose.13

The authors of the Texas study attribute the decline in serious ADEs to the

implementation of blame-free RCA, which prompted important leadership focus and policy

changes related to safety issues. Other changes consisted of improvements in numerous aspects

of the medication ordering and distribution processes (eg, the application of “forcing” and

“constraining” functions that make it impossible to perform certain common errors), as well as

more general changes in organizational features, such as staffing levels.

The significance of the decline in ADEs and its relationship to RCA in the Texas study is

unclear. As the study followed a highly publicized, fatal ADE at the hospital, other cultural or

systems changes may have contributed to the measured effect. The authors were unable to

identify a control group, nor did they report data from serious ADEs in the year preceding the

study. Their data may reflect underreporting, as there is no active surveillance for ADEs at the

study hospital, leaving the authors to rely on voluntary reports. The decline in reported ADEs

may actually call into question the robustness of their reporting system as other studies have

found that instituting a blame-free system leads to large increases in event reporting.5

 On the

other hand, it seems unlikely that serious ADEs would be missed in a culture of heightened

sensitivity to error.

In a separate report, an event reporting system for transfusion medicine was implemented

at 2 blood centers and 2 transfusion services.25 Unique events were subjected to RCA, and all

events were classified using a model adapted from the petrochemical industry.21 There were 503

events reported and 1238 root causes identified. Human failure accounted for 46% of causes,

27% were due to technical failures, and 27% were from organizational failures. This distribution

was very similar to that seen in the petrochemical industry, perhaps an indication of the

universality of causes of error in complex systems, regardless of industry.

Potential for Harm

The potential for harm with the use of RCA has received only passing mention in the

literature, but might result from flawed analyses.31 The costs of pursuing absolute safety may be

the implementation of increasingly complex and expensive safeguards, which in themselves are

prone to systems failures.4,16 Ill-conceived RCAs which result in little effective systems

improvement could also dampen enthusiasm for the entire quality improvement process.

Arguably the harm caused by pursuit of incorrect root causes must be offset by the costs of not

pursuing them at all.

Costs and Implementation

No estimates of costs of RCA have appeared in the literature, but as it is a labor-intensive

process they are likely significant. Counterproductive cultural norms and medico-legal concerns

similar to those seen in incident reporting may hinder implementation of RCA.12,26 The authors

of the Texas study note the importance of clear expressions of administrative support for the

process of blame-free RCA.13 Other studies note the receptiveness of respondents to blame-free
55

investigation in the name of quality improvement, with one health system reporting a sustained

10-fold increase in reporting.25,27

Comment

Root cause analyses systematically search out latent or system failures that underlie

adverse events or near misses. They are limited by their retrospective and inherently speculative

nature. There is insufficient evidence in the medical literature to support RCA as a proven

patient safety practice, however it may represent an important qualitative tool that is

complementary to other techniques employed in error reduction. When applied appropriately,

RCA may illuminate targets for change, and, in certain health care contexts, may generate

testable hypotheses. The use of RCA merits more consideration, as it lends a formal structure to

efforts to learn from past mistakes.

References

1. Sazama K. Current good manufacturing practices for transfusion medicine. Transfus Med

Rev. 1996;10:286-295.

2. Food and Drug Administration: Biological products; reporting of errors and accidents in

manufacturing. Fed Regist. 1997;62:49642-49648.

3. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion.

1990;30:583-590.

4. Reason JT. Human Error. New York: Cambridge Univ Press. 1990.

5. Battles JB, Kaplan HS, Van der Schaaf TW, Shea CE. The attributes of medical eventreporting systems: experience with a prototype medical event-reporting system for

transfusion medicine. Arch Pathol Lab Med. 1998;122:231-238.

6. Eagle CJ, Davies JM, Reason J. Accident analysis of large-scale technological disasters

applied to an anaesthetic complication. Can J Anaesth. 1992;39:118-122.

7. Vincent C, Ennis M, Audley RJ. Medical accidents. Oxford ; New York: Oxford

University Press. 1993.

8. Joint Commission on the Accreditation of Healthcare Organizations. Sentinel event policy

and procedures. Available at: http://www.JCAHO.org/sentinel/se_pp.html. Accessed May

30, 2001.

9. Reason JT. Managing the Risks of Organizational Accidents: Ashgate Publishing

Company. 1997.

10. Reason J. Human error: models and management. BMJ. 2000;320:768-770.

11. Leape LL. Error in medicine. JAMA. 1994;272:1851-1857.

12. Berman S. Identifying and addressing sentinel events: an Interview with Richard Croteau.

Jt Comm J Qual Improv. 1998;24:426-434.

13. Rex JH, Turnbull JE, Allen SJ, Vande Voorde K, Luther K. Systematic root cause analysis

of adverse drug events in a tertiary referral hospital. Jt Comm J Qual Improv. 2000;26:563-

575.

14. Runciman WB, Sellen A, Webb RK, Williamson JA, Currie M, Morgan C, et al. The

Australian Incident Monitoring Study. Errors, incidents and accidents in anaesthetic

practice. Anaesth Intensive Care. 1993;21:506-519.

15. Caplan RA, Posner KL, Cheney FW. Effect of outcome on physician judgments of

appropriateness of care. JAMA. 1991;265:1957-1960.

16. Perrow C. Normal accidents : Living with High-Risk Technologies. With a New Afterword

and a Postscript on the Y2K Problem. Princeton, NJ: Princeton University Press. 1999.
56

17. Rasmussen J. Human error and the problem of causality in analysis of accidents. Philos

Trans R Soc Lond B Biol Sci. 1990;327:449-460.

18. Pope C, Mays N. Reaching the parts other methods cannot reach: an introduction to

qualitative methods in health and health services research. BMJ. 1995;311:42-45.

19. Giacomini MK, Cook DJ. Users' guides to the medical literature: XXIII. Qualitative

research in health care A. Are the results of the study valid? Evidence-Based Medicine

Working Group. JAMA. 2000;284:357-362.

20. Giacomini MK, Cook DJ. Users' guides to the medical literature: XXIII. Qualitative

research in health care B. What are the results and how do they help me care for my

patients? Evidence-Based Medicine Working Group. JAMA. 2000;284:478-482.

21. Van der Schaaf T. Near miss reporting in the Chemical Process Industry [Doctoral thesis].

Eindhoven, The Netherlands: Eindhoven University of Technology. 1992.

22. Moray N. Error reduction as a systems problem. In: Bogner M, editor. Human error in

medicine. Hillsdale, NJ: Lawrence Erlbaum Associates. 1994.

23. Ishikawa K. What is total quality control? The Japanese way. Englewood Cliffs, NJ:

Prentice Hall. 1985.

24. Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Statistics.

Available at: http://www.JCAHO.org. Accessed April 16, 2001.

25. Kaplan HS, Battles JB, Van der Schaaf TW, Shea CE, Mercer SQ. Identification and

classification of the causes of events in transfusion medicine. Transfusion. 1998;38:1071-

1081.

26. Will hospitals come clean for JCAHO? Trustee. 1998;51:6-7.

27. Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan T, et al. Systems

analysis of adverse drug events. ADE Prevention Study Group. JAMA. 1995;274:35-43.

28. Bhasale A. The wrong diagnosis: identifying causes of potentially adverse events in

general practice using incident monitoring. Fam Pract. 1998;15:308-318.

29. Troidl H. Disasters of endoscopic surgery and how to avoid them: error analysis. World J

Surg. 1999;23:846-855.

30. Fernandes CM, Walker R, Price A, Marsden J, Haley L. Root cause analysis of laboratory

delays to an emergency department. J Emerg Med. 1997;15:735-739.

31. Hofer TP, Kerr EA. What is an error? Eff Clin Pract. 2000;3:261-269.
57

PART III. PATIENT SAFETY PRACTICES & TARGETS

Section A. Adverse Drug Events (ADEs)

Section B. Infection Control

Section C. Surgery, Anesthesia, and Perioperative Medicine

Section D. Safety Practices for Hospitalized or Institutionalized Elders

Section E. General Clinical Topics

Section F. Organization, Structure, and Culture

Section G. Systems Issues and Human Factors

Section H. Role of the Patient
58

Section A. Adverse Drug Events (ADEs)

Chapter 6. Computerized Physician Order Entry (CPOE) with Clinical Decision Support

Systems (CDSSs)

Chapter 7. The Clinical Pharmacist’s Role in Preventing Adverse Drug Events

Chapter 8. Computer Adverse Drug Event (ADE) Detection and Alerts

Chapter 9. Protocols for High-Risk Drugs: Reducing Adverse Drug Events Related to

Anticoagulants

Chapter 10. Unit-Dose Drug Distribution Systems

Chapter 11. Automated Medication Dispensing Devices
59

Chapter 6. Computerized Physician Order Entry (CPOE) with Clinical

Decision Support Systems (CDSSs)

Rainu Kaushal, MD, MPH

David W. Bates, MD, MSc

Harvard Medical School

Background

Medication errors and adverse drug events (ADEs) are common, costly, and clinically

important problems.1-7 Two inpatient studies, one in adults and one in pediatrics, have found

that about half of medication errors occur at the stage of drug ordering,2, 7 although direct

observation studies have indicated that many errors also occur at the administration stage.8

 The

principal types of medication errors, apart from missing a dose, include incorrect medication

dose, frequency, or route.2

 ADEs are injuries that result from the use of a drug. Systems-based

analysis of medication errors and ADEs suggest that changes in the medication ordering system,

including the introduction of computerized physician order entry (CPOE) with clinical decision

support systems (CDSSs), may reduce medication-related errors.9

Despite growing evidence and public mandates, implementation of CPOE has been

limited. The Leapfrog Group, a consortium of companies from the Business Roundtable, has

endorsed CPOE in hospitals as one of the 3 changes that would most improve patient safety in

America (see also Chapter 55).10 A Medicare Payment Advisory Commission report suggested

instituting financial incentives for CPOE implementation.11 US Senators Bob Graham (D-Fla.)

and Olympia Snowe (R-Maine) recently introduced a bill, entitled the “Medication Errors

Reduction Act of 2001,” to establish an informatics system grant program for hospitals and

skilled nursing facilities.12 In addition, California recently enacted legislation stipulating that

acute care hospitals implement information technology, such as CPOE to reduce medicationrelated errors.13

Practice Description

CPOE refers to a variety of computer-based systems of ordering medications, which

share the common features of automating the medication ordering process. Basic CPOE ensures

standardized, legible, complete orders by only accepting typed orders in a standard and complete

format. Almost all CPOE systems include or interface with CDSSs of varying sophistication. 

Basic clinical decision support may include suggestions or default values for drug doses, routes,

and frequencies. More sophisticated CDSSs can perform drug allergy checks, drug-laboratory

value checks, drug-drug interaction checks, in addition to providing reminders about corollary

orders (eg, prompting the user to order glucose checks after ordering insulin) or drug guidelines

to the physician at the time of drug ordering (see also Chapter 53).

At times, CDSSs are implemented without CPOE. Isolated CDSSs can provide advice on

drug selection, dosages, and duration. More refined CDSSs can incorporate patient-specific

information (for example recommending appropriate anticoagulation regimens), or incorporate

pathogen-specific information such as suggesting appropriate anti-infective regimens. After

viewing such advice, the physician proceeds with a conventional handwritten medication order.
60

Prevalence and Severity of the Target Safety Problem

It is estimated that over 770,000 people are injured or die in hospitals from ADEs

annually.4, 5, 14 The few hospitals that have studied incidence rates of ADEs have documented

rates ranging from 2 to 7 per 100 admissions.2, 4, 15, 16 A precise national estimate is difficult to

calculate due to the variety of criteria and definitions used by researchers.17 One study of

preventable inpatient ADEs in adults demonstrated that 56% occurred at the stage of ordering,

34% at administration, 6% at transcribing, and 4% at dispensing.2

 In this study, the drug class

most commonly associated with preventable ADEs was analgesics, followed by sedatives and

antibiotics. Even fewer studies have been conducted in the outpatient setting. One recent crosssectional chart review and patient care survey found an ADE rate of 3% in adult primary care

outpatients.18

Opportunities for Impact

Clear data do not exist about the prevalence of CPOE with CDSSs or isolated CDSSs.

One survey of 668 hospitals indicated that 15% had at least partially implemented CPOE.19 A

slightly more recent survey of pharmacy directors at 1050 acute care hospitals in the United

States (51% response rate) reported that 13% of hospitals had an electronic medication orderentry system in place, while an additional 27% stated they were in the process of obtaining such

a sysytem.20

Study Designs

The 4 studies listed in Table 6.1 evaluated CPOE with CDSSs.21-24 The first study, a

randomized controlled trial evaluating the utility of CPOE in improving prescribing for corollary

orders, was conducted by the Regenstrief Institute for Health Care (affiliated with the Indiana

University School of Medicine).21 The remaining 3 studies evaluated the CPOE system at

Brigham and Women’s Hospital (BWH).22-24 Of note, both the Regenstrief and BWH systems

are “home-grown” rather than “off-the-shelf” commercial systems. The first BWH study was a

cross-sectional analysis comparing an intervention period of CPOE with CDSSs for adult

inpatients on medical, surgical, and intensive care wards with a historical period.22 The other 2

BWH studies were time series analyses of orders written for adult inpatients.23, 24

Table 6.2 lists 4 studies25-28 that evaluated isolated CDSSs, 2 of which represent

systematic reviews.25, 26 Hunt et al25 updated an earlier systematic review,29 and included 68

studies that prospectively evaluated use of CDSSs in a clinical setting by a healthcare

practitioner with a concurrent control. Importantly, Hunt et al included studies of outpatient

settings in their review. Walton’s review addressed 15 articles that studied computerized advice

on drug dosage for inpatients.26 Evans et al, at Latter Day Saints Hospital, performed the other 2

studies,27, 28 again on a “home-grown” system. The first was a randomized controlled trial of

empiric antibiotic selection using CDSSs.27 The second study was a cross-sectional analysis

comparing an intervention period of a computer-assisted management program for antiinfectives with a historical control period.28 This second study28 was likely excluded from the

systematic review by Hunt et al25 for methodologic reasons, as it did not have a concurrent

control. The reasons for excluding the first study27 remain unclear. Finally, it is important to

emphasize again that of the primary studies that were included, 6 of 8 were performed at 3

institutions with sophisticated “home-grown” systems. 
61

Study Outcomes

Adverse drug events (ADEs), (injuries that result from the use of drugs) by definition

constitute clinical outcomes (Level 1). ADEs that are associated with a medication error are

considered preventable, while those not associated with a medication error (eg, known

medication side effects) are considered non-preventable. An example of a preventable ADE is

the development of rash after the administration of ampicillin to a known penicillin-allergic

patient. In contrast, a non-preventable ADE would be development of an ampicillin-associated

rash in a patient with no known drug allergies. Non-intercepted serious medication errors include

non-intercepted potential ADEs and preventable ADEs (ie, medication errors that either have the

potential or actually cause harm to a patient).

Medication errors refer to errors in the processes of ordering, transcribing, dispensing,

administering, or monitoring medications, irrespective of the outcome (ie, injury to the patient). 

One example is an order written for amoxicillin without a route of administration. Other

medication errors have a greater potential for patient harm and so are often designated as

“serious medication errors” or “potential ADEs” – eg, an order for amoxicillin in a patient with

past anaphylaxis to penicillin. 

Potential ADEs may or may not be intercepted before reaching the patient. An example

of an intercepted potential ADE would be an order written for an acetaminophen overdose that is

intercepted and corrected by a nurse before reaching the patient. An example of a nonintercepted potential ADE would be an administered overdose of acetaminophen to a patient who

did not suffer any sequelae. 

Medication errors include a mixture of serious medication errors with a significant

potential for patient injury (Level 2) and other deviations from recommended practice that do not

have a clear or established connection to adverse events (Level 3). Examples of the latter

include failure to choose the optimal dosing schedule for a medication and many standards

related to monitoring serum drug levels and routine electrolytes.

Only 2 studies (from a single institution) evaluating CPOE with CDSSs included ADEs

as a secondary outcome (Level 1),22 and even these studies primary outcomes were serious

medication errors (Level 2) and non-intercepted medication errors.23 The other studies reported

a variety of other errors often involving mixtures of Level 2 and Level 3 outcomes – eg,

“prescribing practices”

24 and “corollary orders.”21 Corollary orders refer to orders required to

detect or ameliorate adverse reactions that may result from the trigger order - eg, checking the

serum creatinine a minimum of 2 times per week in a patient receiving a nephrotoxic agent such

as amphotericin. Many corollary orders capture Level 3 outcomes, as failure to prescribe these

orders would in most cases have no clear impact on clinical outcomes – eg, failure to order daily

tests for fecal occult blood in patients on heparin or screening audiometry for patients receiving

vancomycin.21

The predominance of Level 2 and 3 outcomes in these studies is understandable, given

the much higher frequency of these outcomes compared to actual ADEs and the enormous costs

of conducting these studies. 

Similarly, the studies evaluating CDSSs reported a mixture of outcomes from Levels 1-3.

 Hunt et al reviewed articles to determine changes in patient outcomes (Level 1) or physician

performance (Levels 2 and 3, depending on the practice).25 Walton et al evaluated a range of

outcomes (Levels 1-3), including reductions in “adverse reactions and unwanted effects” (Level

1).26 In one study, Evans et al determined rates of pathogen susceptibility to an antibiotic
62

regimen27 (Level 2); another study by the same authors evaluated adverse drug events caused by

anti-infectives as a main outcome (Level 1).28

Evidence for Effectiveness of the Practice

Of the 2 studies at BWH that addressed the impact of CPOE with CDSSs on medication

errors and ADEs, the first demonstrated a 55% decrease in serious medication errors.22 As a

secondary outcome, this study found a 17% decrease in preventable ADEs, which was not

statistically significant. The second study, a time series analysis, demonstrated marked

reductions in all medication errors excluding missed dose errors and in non-intercepted serious

medication errors.23 The number of ADEs in this study was quite small – 25 in the baseline

period and 18 in the third of the 3 periods with CPOE and CDSS. Correcting for the number of

opportunities for errors, the total number of ADEs/1000 patient days decreased from 14.7 to 9.6

(p=0.09). For the sub-category of preventable ADEs, the reduction (from 5 to 2) achieved

borderline statistical significance (p=0.05).

Overhage et al and Teich et al studied more focused aspects of the medication system. 

Overhage et al21 studied computerized reminders for corollary orders (eg, entering a laboratory

order to check electrolytes when ordering potassium for a patient) and showed a greater than

100% improvement in the rate of corollary orders (p<0.0001). Teich et al24 studied a broad

range of computerized clinical decision support tools utilized at BWH and demonstrated 5

prescribing improvements in types, doses, and frequencies of drug usage.

In summary, these studies provide some evidence that CPOE with CDSSs can

substantially decrease medication errors in broad as well as in more focused areas. Despite the

significant impact on medication errors, the reduction in ADEs did not achieve statistical

significance in one study,22 and achieved only borderline significance in one of the outcomes in

the other study.23 Furthermore, the systems evaluated in this relatively small literature were

developed internally rather than purchased and installed, so the potential impact of commercially

available systems remains somewhat speculative.

In the studies evaluating CDSSs, 2 were systematic reviews.25, 26 In Hunt’s review,

which emphasized clinical performance, 6 of 14 studies reported improvements in patient

outcomes and 43 of 65 studies showed improvement in physician performance.25 This study

concludes that CDSSs can enhance clinical performance for drug dosing, preventive care, and

other aspects of medical care, but that the impact of CDSSs on patient outcomes remains unclear

(see also Chapter 53). Walton’s systematic review evaluated computerized drug dosage advice

and found a 6% decrease in adverse drug reactions.26 The authors concluded that there is some

limited evidence that CDSSs for drug dosing are effective, however there are relatively few

studies, many of which are of sub-optimal quality. They also suggest that further research is

needed to determine if the CDSS benefits realized with specialist applications can be realized by

generalist use. Evans et al performed the remaining 2 studies.27, 28 The 1994 study evaluated the

use of a computerized antibiotic selection consultant, and demonstrated a 17% greater pathogen

susceptibility to an antibiotic regimen suggested by a computer consultant versus a physician

(p<0.001).27 The second study demonstrated a 70% decrease in ADEs caused by anti-infectives

(p=0.018) through use of a computer based anti-infective management program. As with CPOE,

these CDSSs studies demonstrate improvements in medication errors with statistical

significance. In addition, both Walton’s systematic review26 and the latter study by Evans et al28

demonstrated significant decreases in ADEs. Importantly, each of these CDSSs studies only

addressed focal aspects of the medication system. In addition, relatively little information is

available about the differences between systems.
63

Potential for Harm

Faulty decision support data, for example an incorrect default dosing suggestion, can lead

to inappropriate ordering choices by physicians. The BWH time series analysis demonstrated an

initial rise in intercepted potential ADEs due to the structure of the ordering screen for potassium

chloride.23 This structural error was identified and easily rectified, but underscores the

importance of close scrutiny of all aspects of CPOE screens, both initially and on an ongoing

basis.23

Also, analogously to writing an order in the wrong patient chart in a conventional system,

a physician can electronically write an order in the wrong patient’s record - eg, after walking

away from the terminal, opening the wrong record from a personalized rounding list. In

addition, it is critical that the trigger level for warnings appropriately balances alarm sensitivity

and specificity. These systems must have thresholds set so that physicians receive warnings in

situations with a potential for significant harm, without being overwhelmed by “false alarms.”

Another potential risk is hardware outage or software instability. For example, the reliability

that is needed with CPOE is much higher than that required for systems that simply report

laboratory results.

Costs and Implementation

Six of the studies described in this review evaluated “home-grown” rather than “off-theshelf” systems. The present costs for purchasing commercial systems are substantially more

than the previous costs of developing such systems. For BWH, the cost of developing and

implementing CPOE in 1992 was estimated to be $1.9 million, with maintenance costs of

$500,000 per year. In comparison, the cost of purchasing and implementing large commercial

systems varies substantially, but may be on the order of tens of millions of dollars. Several

studies demonstrate that only minimal resources are needed to introduce and/or maintain

decision support programs into existing order entry programs.21, 24, 30

Relatively few data are available regarding the financial benefits of CPOE, although they

extend well beyond medication-related events. The net savings of the BWH system are

estimated at $5-10 million per year.31 It is estimated that the costs to BWH for preventable

ADEs are $2.8 million annually.32 Evans et al reported a $100,000 per year cost avoidance with

a computer-assisted antibiotic dosing program largely attributable to decreased antibiotic use and

avoided ADEs.33

Importantly, healthcare systems must garner both financial and organizational support

before introducing CPOE with CDSSs. CPOE requires a very large up-front investment with

more remote, albeit substantial returns. In addition, CPOE impacts clinicians and workflow

substantially. Its complexity requires close integration with multiple systems, such as the

laboratory and pharmacy systems. Failure to attend to the impact of such a large-scale effort on

organizational culture and dynamics may result in implementation failure.34 Therefore, it is

essential to have organizational support and integration for its successful implementation and

use.

Comment

The literature supports CPOE’s beneficial effect in reducing the frequency of a range of

medication errors, including serious errors with the potential for harm. Fewer data are available

regarding the impact of CPOE on ADEs, with no study showing a significant decrease in actual

patient harm. Similarly, isolated CDSSs appear to prevent a range of medication errors, but with
64

few data describing reductions in ADEs or improvements in other clinical outcomes. Finally, the

studied CDSSs address focused medication use (for example, antibiotic dosing) rather than more

general aspects of medication use.

Further research should be conducted to compare the various types of systems and to

compare “home-grown” with commercially available systems. Such comparisons are

particularly important since the institutions that have published CPOE outcomes have generally

been those with strong institutional commitments to their systems. Whether less committed

institutions purchasing “off the shelf” systems will see benefits comparable to those enjoyed by

“pioneers” with home-grown systems remains to be determined. Studying the benefits of such

complex systems requires rigorous methodology and sufficient size to provide the power to

study ADEs. Further research also needs to address optimal ways for institutions to acquire and

implement computerized ordering systems.
65

Table 6.1. Studies of computerized physician order entry (CPOE) with clinical decision

support systems (CDSSs)*

Study Study Design Study Outcomes Results

Overhage, 1997.21 Impact of

faculty and physician

reminders (using CPOE) on

corollary orders for adult

inpatients in a general medical

ward at a public teaching

hospital affiliated with the

Indiana University School of

Medicine

Level 1

(RCT with

physicians

randomized

to receive

reminders or

not)

Levels 2 & 3

(errors of omission

in corollary orders)

25% improvement in

ordering of corollary

medications by faculty

and residents

(p<0.0001)

Bates, 1998.22 CPOE with

CDSSs for adult inpatients on

medical, surgical, and intensive

care wards at BWH, a tertiary

care center affiliated with

Harvard University

Levels 2 & 3

(two study

designs)

Level 1 (ADE

rates) and Level 2

(serious

medication errors)

55% decrease in nonintercepted serious

medication errors

(p=0.01)

17% decrease in

preventable ADEs

(p=0.37)

Bates, 1999.23 CPOE with

CDSSs for adult inpatients in 3

medical units at BWH

Level 3

(retrospective

time series)

Level 1 (ADEs)

and Level 2 (main

outcome measure

was medication

errors)

81% decrease in

medication errors

(p<0.0001)

86% decrease in nonintercepted serious

medication errors

(p=0.0003)

Teich, 2000.24 CPOE with

CDSSs for all adult inpatients at

BWH 

Level 3

(retrospective

before-after

analysis)

Levels 2 & 3

(changes in 5

prescribing

practices)

Improvement in 5

prescribing practices

(p<0.001 for each of

the 5 comparisons) * ADE indicates adverse drug event; BWH, Brigham and Women’s Hospital; and RCT,

randomized controlled trial.
66

Table 6.2. Studies of clinical decision support systems (CDSSs)*

Study Setting Study Design Study Outcomes Results

Hunt, 1998.25 Use of

CDSSs by healthcare

practitioners in

multiple inpatient and

outpatient settings

Level 1A

(systematic

review of RCTs)

Levels 1 & 2 (a

variety of measures

related to patient

outcomes and

physician practice, not

just ADEs and

processes of care

related to medication

use.

6 of 14 studies showed

improvement in patient

outcomes

43 of 65 studies

showed improvement

in physician

performance

Walton, 2001.26 Use of

CDSSs for drug dosage

advice by healthcare

practitioners for 1229

patients in multiple

inpatient settings

Levels 1A-3A

(systematic

review of RCTs,

interrupted time

series analyses,

and controlled

before-after

studies)

Level 1 (one main

outcome measure was

adverse drug reactions

Absolute risk reduction

with CDSSs: 6% (95%

CI: 0-12%)

Evans, 1994.27 Use of a

computerized antibiotic

selection consultant for

451 inpatients at Salt

Lake City’s LDS

Hospital, a 520-bed

community teaching

hospital and tertiary

referral center

Level 1 (RCT

with crossover

design)

Level 2 (one of 5

primary outcomes was

pathogen

susceptibility to

prescribed antibiotic

regimens

17% greater pathogen

susceptibility to an

antibiotic regimen

suggested by computer

consultant versus

physicians (p<0.001)

Evans, 1998.28

Computer-based antiinfective management

program for 1136

intensive care unit

patients from a 12-bed

ICU at LDS Hospital

Level 2

(prospective

before-after

analysis)

Level 2 (one primary

outcome was ADEs

due to anti-infective

agents

70% decrease in ADEs

caused by antiinfectives (p=0.02)

* ADE indicates adverse drug event; CI, confidence interval; ICU, intensive care unit; and RCT,

randomized controlled trial.
67

References

1. Barker KN, Mikeal RL, Pearson RE, Illig NA, Morse ML. Medication errors in nursing

homes and small hospitals. Am J Hosp Pharm. 1982; 39: 987-91.

2. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of

adverse drug events and potential adverse drug events: Implications for prevention.

JAMA. 1995; 274: 29-34.

3. Dean BS, Allan EL, Barber ND, Barker KN. Comparison of medication errors in an

American and British hospital. Am J Health Syst Pharm. 1995; 52: 2543-49.

4. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in

hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA.

1997; 277: 301-6.

5. Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable

adverse drug events in hospitalized patients: a comparative study of intensive care and

general care units. Crit Care Med. 1997; 25: 1289-97.

6. Lesar TS, Lomaestro BM, Pohl H. Medication-prescribing errors in a teaching hospital.

A 9-year experience. Arch Intern Med. 1997; 157: 1569-76.

7. Kaushal R, Bates DW, Landrigan C, McKenna J, Clapp MD, Federico F, et al.

Medication Errors and Adverse Drug Events in Pediatric Inpatients. JAMA. 2001; 285:

2114-20.

8. Allan EL, Barker KN. Fundamentals of medication error research. Am J Hosp Pharm.

1990; 47: 555-71.

9. Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan T, et al. Systems

analysis of adverse drug events. ADE Prevention Study Group. JAMA. 1995; 274: 35-43.

10. Milstein A, Galvin RS, Delbanco SF, Salber P, Buck Jr CR. Improving the safety of

health care: the leapfrog initiative. Eff Clin Pract. 2000; 3: 313-6.

11. The Medicare Payment Advisory Commission. Report to the Congress. Selected

Medicare Issues. Available at: http://www.medpac.gov/. Accessed May 21, 2001.

12. United States Senate. Press Release. Available at:

http://www.senate.gov/~graham/pr050301.html. Accessed June 12, 2001.

13. California Senate Bill No. 1875. Chapter 816, Statutes of 2000. (Sept. 28, 2000)

14. Cullen DJ, Bates DW, Small SD, Cooper JB, Nemeskal AR, Leape LL. The incident

reporting system does not detect adverse drug events: a problem for quality

improvement. Jt Comm J Qual Improv. 1995; 21: 541-8.
68

15. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between

medication errors and adverse drug events. J Gen Intern Med. 1995; 10: 199-205.

16. Jha AK, Kuperman GJ, Teich JM, Leape L, Shea B, Rittenberg E, et al. Identifying

adverse drug events: development of a computer-based monitor and comparison with

chart review and stimulated voluntary report. J Am Med Inform Assoc. 1998; 5: 305-14.

17. Adverse drug events: the magnitude of health risk is uncertain because of limited

incidence data. Washington, D.C.: General Accounting Office; 2000.

18. Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, et al. Drug

Complications in Outpatients. J Gen Intern Med. 2000; 15: 149-54.

19. Ash JS, Gorman PN, Hersh WR. Physician order entry in U.S. hospitals. Proceedings

AMIA Annual Symposium. 1998: 235-39.

20. Ringold DJ, Santell JP, Schneider PJ. ASHP national survey of pharmacy practice in

acute care settings: dispensing and administration--1999. Am J Health Syst Pharm. 2000;

57: 1759-75.

21. Overhage JM, Tierney WM, Zhou XH, McDonald CJ. A randomized trial of "corollary

orders" to prevent errors of omission. J Am Med Inform Assoc. 1997; 4: 364-75.

22. Bates DW, Leape LL, Cullen DJ, Laird N, Petersen LA, Teich JM, et al. Effect of

computerized physician order entry and a team intervention on prevention of serious

medication errors . JAMA. 1998; 280: 1311-6.

23. Bates DW, Teich JM, Lee J, Seger D, Kuperman GJ, Ma'Luf N, et al. The impact of

computerized physician order entry on medication error prevention. J Am Med Inform

Assoc. 1999; 6: 313-21.

24. Teich JM, Merchia PR, Schmiz JL, Kuperman GJ, Spurr CD, Bates DW. Effects of

computerized physician order entry on prescribing practices. Arch Intern Med. 2000;

160: 2741-7.

25. Hunt DL, Haynes RB, Hanna SE, Smith K. Effects of computer-based clinical decision

support systems on physician performance and patient outcomes: a systematic review.

JAMA. 1998; 280: 1339-46.

26. Walton RT, Harvey E, Dovey S, Freemantle N. Computerised advice on drug dosage to

improve prescribing practice (Cochrane Review). In: The Cochrane Library, Issue 2,

2001. Oxford: Update Software.

27. Evans RS, Classen DC, Pestotnik SL, Lundsgaarde HP, Burke JP. Improving empiric

antibiotic selection using computer decision support. Arch Intern Med. 1994; 154: 878-

84.
69

28. Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver LK, Orme JF, Jr., et al. A

computer-assisted management program for antibiotics and other antiinfective agents. N

Engl J Med. 1998; 338: 232-8.

29. Johnston ME, Langton KB, Haynes RB, Mathieu A. Effects of computer-based clinical

decision support systems on clinician performance and patient outcome. A critical

appraisal of research . Ann Intern Med. 1994; 120: 135-42.

30. Shojania KG, Yokoe D, Platt R, Fiskio J, Ma'luf N, Bates DW. Reducing vancomycin

use utilizing a computer guideline: results of a randomized controlled trial. J Am Med

Inform Assoc. 1998; 5: 554-62.

31. Teich JM, Glaser JP, Beckley RF, Aranow M, Bates DW, Kuperman GJ, et al. Toward

cost-effective, quality care; the Brigham Integrated Computing System. Proc. 2nd

Nicholas E. Davies CPR Recognition Symposium. Washington, D.C.: Computerized

Patient Record Institute. 1996;3-34.; 1996: 3-34.

32. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of

adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study

Group. JAMA. 1997; 277: 307-11.

33. Evans RS, Pestonik SL, Classen DC, Burke JP. Evaluation of a computer-assisted

antibiotic-dose monitor. Ann Pharmacother. 1999; 33: 1026-31.

34. Massaro TA. Introducing physician order entry at a major academic medical center: I.

Impact on organizational culture and behavior. Acad Med. 1993; 68: 20-5.
70
71

Chapter 7. The Clinical Pharmacist’s Role in Preventing Adverse Drug

Events

Rainu Kaushal, MD, MPH

David W. Bates, MD, MSc

Harvard Medical School

Background

A large literature documents the multiple roles clinical pharmacists can play in a variety

of health care settings.1-8 Much of this literature focuses on measures of impact not directly

relevant to this Report – eg, economic benefits,4,8 patient compliance,6

 and drug monitoring.2,3

More recently, systems-based analyses of medication errors and adverse drug events (ADEs)

have drawn attention to the impact clinical pharmacists can exert on the quality and safety of

medication use.9-12 In this chapter, we review the evidence supporting the premise that direct

participation of pharmacists’ in clinical care reduces medication errors and ADEs in hospitalized

and ambulatory patients.

Practice Description

Clinical pharmacists may participate in all stages of the medication use process,

including drug ordering, transcribing, dispensing, administering, and monitoring. The specific

activities of clinical pharmacists vary substantially in the studies reviewed in this chapter. In the

hospital setting, one study evaluated the role of a senior pharmacist participating fully in

intensive care unit rounds and available throughout the day in person or by page for questions.13

Another study evaluated a ward pharmacy service that examined order sheets for new therapies

and carried out checks that were formerly performed in the pharmacy.14

Pharmacists may also play a role at the time of discharge. One study reported the impact

of clinical pharmacists’ consultation for geriatric patients at the time of discharge,15 with

pharmacists serving as consultants to physicians and reinforcing patients’ knowledge of their

medication regimen. The roles of clinical pharmacists are similarly diverse in studies of

ambulatory settings. Here they include the provision of consultative services,16-18 patient

education,16-18 therapeutic drug monitoring,3

 and even follow-up telephone calls to patients.3,16-18

Prevalence and Severity of the Target Safety Problem

It is estimated that over 770,000 people are injured or die in hospitals from adverse drug

events (ADEs) annually.19-21 The few hospitals that have studied incidence rates of ADEs have

documented rates ranging from 2 to 7 per 100 admissions.11,19,22,23 A precise national estimate is

difficult to calculate due to the variety of criteria and definitions used by researchers.24 One

study of preventable inpatient ADEs in adults demonstrated that 56% occurred at the stage of

ordering, 34% at administration, 6% at transcribing, and 4% at dispensing.22 In this study, the

drug class most commonly associated with preventable ADEs was analgesics, followed by

sedatives and antibiotics. Even fewer studies have been conducted in the outpatient setting. One

recent cross-sectional chart review and patient care survey found an ADE rate of 3% in adult

primary care outpatients.25

Opportunities for Impact

Although many hospital pharmacy departments offer clinical pharmacy consultation

services,26 the degree to which these services include rounding with clinicians13 is unclear.
72

Hospital pharmacies provide support to a variable degree in different ambulatory settings

(clinics, nursing homes, adult daycare),26 but the precise nature of clinical pharmacists’ activities

in these settings is not uniformly characterized.

Study Designs

We identified 3 systematic reviews of clinical pharmacists in the outpatient setting.5,17,18

We included only the most recent review,18 as it followed the most rigorous methodology and

included the bibliographies of the previous reviews.5,17 We identified only one study16 of the

impact of clinical pharmacists on patient outcomes in the ambulatory setting that had not been

included in this systematic review.18 This study, a randomized controlled trial evaluating clinical

pharmacists’ participation in the management of outpatients with congestive heart failure,16 was

therefore also included.

For studies of clinical pharmacists in the hospital setting, an older review2

 did not meet

the characteristics of a systematic review, but was a very thorough summary of the relevant

literature. It included 8 studies evaluating pharmacists’ roles in detecting and reporting ADEs in

the hospital setting. Preliminary review of these studies revealed that the measured outcomes

were Level 3 (detection of ADEs as an end in itself). Consequently, we did not include them.

One older retrospective before-after analysis (Level 3)14 did meet our inclusion criteria, as did 2

more recent studies of clinical pharmacists’ roles in the inpatient setting: a prospective,

controlled before-after study (Level 2)13 and a randomized controlled trial (Level 1).15

We included an additional meta-analysis focusing on therapeutic drug monitoring by

clinical pharmacists in the hospital and ambulatory settings.3

 The studies included in this metaanalysis consisted predominantly of controlled observational studies (Level 3) and nonrandomized clinical trials (Level 2), but one randomized controlled trial was also included (Level

1-3A).

Table 7.1 lists the studies reviewed in this chapter and briefly describes their salient

features. All of the listed studies involved adult patients, as the single pediatric study9

 identified

by our literature search had no control group (Level 4 design) and was therefore excluded.

Study Outcomes

Level 1 outcomes reported in the included studies consisted of ADEs13 and clinical

events related to heart failure, including mortality.16 One study used telephone interviews to

solicit patient self-reports of adverse drug reactions.13,27 This study was excluded since the

systematic review of clinical pharmacists’ roles in ambulatory settings18 incorporated its findings

in several of its analyses.

The distinction between Level 2 and 3 outcomes can be somewhat ambiguous in studies

of prescribing practice, as the exact point at which choices of therapeutic agents or dosing

patterns become not just sub-optimal but actually represent “errors” is difficult to define

precisely. Even for objective outcomes, such as serum drug concentrations, the connection to

patient outcomes is weak in some cases (eg, monitoring vancomycin levels28,29), and therefore

more appropriately designated as Level 3 rather than Level 2. Acknowledging the subjectivity of

this judgment in some cases, we included studies that contained a mixture of Level 2 and 3

outcomes, including “prescribing problems,” (which included inappropriate choice of therapy,

dosage errors, frequency errors, drug-drug interactions, therapeutic duplications, and allergies15),

and serum drug concentrations for a broad range of medications.3
73

Evidence for Effectiveness of the Practice

In the inpatient setting, Leape’s study13 demonstrated a statistically significant 66%

decrease in preventable ADEs due to medication ordering. The study of geriatric patients at the

time of discharge demonstrated clinically and statistically significant decreases in medication

errors.15 The meta-analysis of the effect of clinical pharmacokinetics services on maintaining

acceptable drug ranges indicated only modest effect sizes for the outcomes measured, and only 2

of the main results achieved statistical significance.3

The comprehensive review of clinical pharmacist services in ambulatory settings reported

positive impacts for patients with hypertension, hypercholesterolemia, chronic heart failure, and

diabetes.18 However, the authors identify important limitations: these studies are not easily

generalizable, only 2 studies compared pharmacist services with other health professional

services, and both studies had important biases. Consequently, they emphasized the need for

more rigorous research to document the effects of outpatient pharmacist interventions.18 The

additional study of outpatients demonstrated significant decreases in mortality and heart failure

events,16 but these results may reflect closer follow-up and monitoring (including telemetry) for

the intervention group or the higher doses of angiotensin-converting enzyme (ACE) inhibitors

the patients received. Generalizing this benefit to other conditions is difficult since most

conditions do not have a single medication-related process of care that delivers the marked

clinical benefits as do ACE inhibitors in the treatment of congestive heart failure.30

Potential for Harm

Introducing clinical pharmacists might potentially disrupt routine patient care activities.

However, the 2 studies that assessed physician reactions to clinical pharmacists13,27 found

excellent receptivity and subsequent changes in prescribing behavior.

Costs and Implementation

Two studies examined resource utilization and cost savings in the inpatient setting. The

intensive care unit study indicated that there could be potential savings of $270,000 per year for

this hospital if the intervention involved re-allocation of existing pharmacists’ time and

resources.13 McMullin et al studied all interventions made by 6 hospital pharmacists over a onemonth period at a large university hospital and estimated annual cost savings of $394,000.31

A systematic review of outpatient pharmacists indicated that pharmacist interventions

could lead to increased scheduled service utilization and decreased non-scheduled service

utilization, specialty visits, and numbers and costs of drugs.18
74

Comment

At present, one study provides strong evidence for the benefit of clinical pharmacists in

reducing ADEs in hospitalized intensive care unit patients.13 One additional study provides

modest support for the impact of ward-based clinical pharmacists on the safety and quality of

inpatient medication use.14 The evidence in the outpatient setting is less substantial, and not yet

convincing. Given the other well-documented benefits of clinical pharmacists and the promising

results in the inpatient setting, more focused research documenting the impact of clinical

pharmacist interventions on medication errors and ADEs is warranted.
75

Table 7.1. Studies of clinical pharmacists’ impact on ADEs and medication errors*

Study Study Design Study Outcomes Results

Beney, 2000.18 Systematic

review of the roles and impacts

of pharmacists in ambulatory

settings; reviewed studies

included 16,000 outpatients

and 40 pharmacists

Level 1A

(systematic

review)

Levels 1-3

(variety of patient

outcomes, surrogate

outcomes, impacts on

physician prescribing

practices and measures of

resource use)

Improvement in outcomes for

patients with hypertension,

hypercholesterolemia,

chronic heart failure, and

diabetes

Gattis, 1999.16 181 patients

with heart failure due to left

ventricular dysfunction

followed in a general

cardiology clinic

Level 1

(RCT)

Level 1

(mortality and other

clinical outcomes related

to heart failure)

16 versus 4 deaths or other

heart failure events (p<0.005)

Leape, 1999.13 Medical and

cardiac intensive care unit

patients at Massachusetts

General Hospital, a tertiary

care hospital in Boston

Level 2

(prospective

before-after study

with concurrent

control)

Level 1 (ADEs) 66% decrease in the rate of

preventable ADEs (p<0.001)

Leach, 1981.14 315 patients at

Queen Elizabeth Hospital in

Birmingham, England

Level 3

(retrospective

before-after

analysis)

Level 2

(various types of

medication errors)

40-50% overall reduction in

medication errors

All 8 of the targeted error

types decreased (results

achieved statistical

significance for 5 error types)

Lipton, 1992.15 236 geriatric

patients discharged from the

hospital on three or more

medications

Level 1 Levels 2 & 3

(“prescribing problems”)

Less likely to have a

“prescribing problem”

(p=0.05)

Ried, 1989.3 Pooled patient

population not reported, but

review of articles indicates

predominance of studies of

(mostly adult) hospitalized

patients

Level 1A-3A

(meta-analysis

predominantly

included controlled

observational

studies and nonrandomized trials)

Levels 2 & 3

(measures of peak,

trough and toxic serum

drug concentrations for a

variety of medications)

More likely to have

therapeutic peak and trough

and less likely to have toxic

peak and trough, but modest

effect sizes (results achieved

statistical significance for

only 2 measures)

* ADE indicates adverse drug event; and RCT, randomized controlled trial.
76

References

1. Dyer CC, Oles KS, Davis SW. The role of the pharmacist in a geriatric nursing home: a

literature review. Drug Intell Clin Pharm. 1984;18:428-433.

2. Hatoum HT, Catizone C, Hutchinson RA, Purohit A. An eleven-year review of the

pharmacy literature: documentation of the value and acceptance of clinical pharmacy. Drug

Intell Clin Pharm. 1986;20:33-48.

3. Ried LD, McKenna DA, Horn JR. Meta-analysis of research on the effect of clinical

pharmacokinetics services on therapeutic drug monitoring. Am J Hosp Pharm.

1989;46:945-951.

4. Willett MS, Bertch KE, Rich DS, Ereshefsky L. Prospectus on the economic value of

clinical pharmacy services. A position statement of the American College of Clinical

Pharmacy. Pharmacotherapy. 1989;9:45-56.

5. Carter BL, Helling DK. Ambulatory care pharmacy services: the incomplete agenda. Ann

Pharmacother. 1992;26:701-708.

6. Tett SE, Higgins GM, Armour CL. Impact of pharmacist interventions on medication

management by the elderly: a review of the literature. Ann Pharmacother. 1993;27:80-86.

7. Jenkins MH, Bond CA. The impact of clinical pharmacists on psychiatric patients.

Pharmacotherapy. 1996;16:708-714.

8. Schumock GT, Meek PD, Ploetz PA, Vermeulen LC. Economic evaluations of clinical

pharmacy services–1988-1995. The Publications Committee of the American College of

Clinical Pharmacy. Pharmacotherapy. 1996;16:1188-1208.

9. Folli HL, Poole RL, Benitz WE, Russo JC. Medication error prevention by clinical

pharmacists in two children's hospitals. Pediatrics. 1987;79:718-722.

10. Lesar TS, Briceland LL, Delcoure K, Parmalee JC, Masta-Gornic V, Pohl H. Medication

prescribing errors in a teaching hospital. JAMA. 1990;263:2329-2334.

11. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between

medication errors and adverse drug events. J Gen Intern Med. 1995;10:199-205.

12. Kaushal R, Bates DW, Landrigan C, McKenna J, Clapp MD, Federico F, et al. medication

errors and adverse drug events in pediatric inpatients. JAMA. 2001;285:2114-2120.

13. Leape LL, Cullen DJ, Clapp MD, Burdick E, Demonaco HJ, Erickson JI, et al. Pharmacist

participation on physician rounds and adverse drug events in the intensive care unit. JAMA.

1999;282:267-270.

14. Leach RH, Feetam C, Butler D. An evaluation of a ward pharmacy service. J Clin Hosp

Pharm. 1981;6:173-182.

15. Lipton HL, Bero LA, Bird JA, McPhee SJ. The impact of clinical pharmacists'

consultations on physicians' geriatric drug prescribing. A randomized controlled trial. Med

Care. 1992;30:646-658.

16. Gattis WA, Hasselblad V, Whellan DJ, O'Connor CM. Reduction in heart failure events by

the addition of a clinical pharmacist to the heart failure management team: results of the

Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM)

Study. Arch Intern Med. 1999;159:1939-1945.

17. Hatoum HT, Akhras K. 1993 Bibliography: a 32-year literature review on the value and

acceptance of ambulatory care provided by pharmacists. Ann Pharmacother.

1993;27:1106-1119.
77

18. Beney J, Bero LA, Bond C. Expanding the roles of outpatient pharmacists: effects on

health services utilisation, costs, and patient outcomes. In: The Cochrane Library, Issue 2,

2000. Oxford: Update Software.

19. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in

hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA.

1997;277:301-306.

20. Cullen DJ, Bates DW, Small SD, Cooper JB, Nemeskal AR, Leape LL. The incident

reporting system does not detect adverse drug events: a problem for quality improvement.

Jt Comm J Qual Improv. 1995;21:541-548.

21. Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable

adverse drug events in hospitalized patients: a comparative study of intensive care and

general care units. Crit Care Med. 1997;25:1289-1297.

22. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse

drug events and potential adverse drug events: Implications for prevention. JAMA.

1995;274:29-34.

23. Jha AK, Kuperman GJ, Teich JM, Leape L, Shea B, Rittenberg E, et al. Identifying adverse

drug events: development of a computer-based monitor and comparison with chart review

and stimulated voluntary report. J Am Med Inform Assoc. 1998;5:305-314.

24. Adverse drug events: the magnitude of health risk is uncertain because of limited incidence

data. Washington, DC: General Accounting Office; 2000.

25. Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, et al. Drug

complications in outpatients. J Gen Intern Med. 2000;15:149-154.

26. Ringold DJ, Santell JP, Schneider PJ. ASHP national survey of pharmacy practice in acute

care settings: dispensing and administration–1999. Am J Health Syst Pharm.

2000;57:1759-1775.

27. Hanlon JT, Weinberger M, Samsa GP, Schmader KE, Uttech KM, Lewis IK, et al. A

randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate

prescribing in elderly outpatients with polypharmacy. Am J Med. 1996;100:428-437.

28. Freeman CD, Quintiliani R, Nightingale CH. Vancomycin therapeutic drug monitoring: is

it necessary? Ann Pharmacother. 1993;27:594-598.

29. Cantu TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations:

reappraisal of their clinical value. Clin Infect Dis. 1994;18:533-543.

30. Flather MD, Yusuf S, Kober L, Pfeffer M, Hall A, Murray G, et al. Long-term ACEinhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic

overview of data from individual patients. ACE-Inhibitor Myocardial Infarction

Collaborative Group. Lancet. 2000;355:1575-1581.

31. McMullin ST, Hennenfent JA, Ritchie DJ, Huey WY, Lonergan TP, Schaiff RA, et al. A

prospective, randomized trial to assess the cost impact of pharmacist-initiated

interventions. Arch Intern Med. 1999;159:2306-2309.
78
79

Chapter 8. Computer Adverse Drug Event (ADE) Detection and Alerts

Tejal K. Gandhi, MD, MPH

David W. Bates, MD, MSc

Harvard Medical School

Background

Adverse drug events (ADEs) occur in both inpatient and outpatient settings.1,2 Most

institutions use spontaneous incident reporting to detect adverse events in general, and ADEs in

particular. Spontaneous incident reporting relies exclusively on voluntary reports from nurses,

pharmacists and physicians focused on direct patient care. However, spontaneous reporting is

ineffective, identifying only one in 20 ADEs.3

 Efforts to increase the frequency of spontaneous

reporting have had only a minor impact.

Several studies demonstrate the effectiveness of using computerized detection and alert

systems (referred to as computer “monitors”) to detect ADEs. In 1991, Classen et al4

 published

information about a computerized ADE monitor that was programmed to identify signals—in

effect mismatches of clinical information—that suggested the presence of an ADE. The signals

included sudden medication stop orders, antidote ordering, and certain abnormal laboratory

values.4

 The computerized signals were then evaluated by a pharmacist who determined whether

an ADE had occured. Based on the rules of this study, Jha et al developed a similar monitor that

identified approximately half the ADEs identified by chart review, at much lower cost.5

Similarly, Bowman and Carlstedt used the Regenstrief Medical Record System to create a

computerized inpatient ADE detection system.6

 Compared to the “gold standard” of chart

review, the monitor had 66% sensitivity and 61% specificity, with a positive predictive value of

0.34. Finally, one community hospital implemented an ADE monitor with triggers that were

reviewed by pharmacists who then contacted physicians to make appropriate regimen changes.

This study identified opportunities to prevent patient injury at a rate of 64/1000 admissions.7

These studies and others demonstrate the potential value of computer monitors, especially when

linked to effective integrated information systems. While monitors are not yet widely used, they

offer an efficient approach for monitoring the frequency of ADEs on an ongoing basis, and the

Health Care Financing Administration is considering mandating them.8

Practice Description

Computerized ADE alert monitors use rule sets to search signals that suggest the

presence of adverse drug events. The most frequently studied rule sets (or “triggers”) are those

that search for drug names (eg, naloxone, kayexalate), drug-lab interactions (eg, heparin and

elevated PTT) or lab levels alone (eg, elevated digoxin levels) that frequently reflect an ADE.

Simple versions can be implemented with pharmacy and laboratory data alone, although the

yield and positive predictive value of signals is higher when the 2 databases are linked.

Further refinements include searches for International Classification of Diseases (ICD-9)

codes, and text-searching of electronic nursing bedside charting notes or outpatient notes for

drug-symptom combinations (eg, medication list includes an angiotensin converting enzyme

inhibitor and the patient notes mention “cough”). Although these refinements do increase the

yield of monitors, they require linkage to administrative databases or electronic medical records.

The information captured with computer monitors is used to alert a responsible clinician

or pharmacist, who can then change therapy based on the issue in question. Systems are designed
80

to alert the monitoring clinician in various ways. Alerts can go to one central location (eg,

hospital pharmacist) or to individual physicians. Monitoring pharmacists typically review the

alert and contact the appropriate physician if they determine that the alert has identified a true

event. The alert modality also varies based on the available technology, from printed out reports,

to automatic paging of covering physicians, to display of alerts on computer systems (either in

results or ordering applications). It should be emphasized that computerized physician order

entry (Chapter 6) is not a requirement for these monitors. Thus, a simple version of this approach

could be implemented in most US hospitals.

Prevalence and Severity of the Target Safety Problem

It is estimated that over 770,000 people are injured or die in hospitals from ADEs

annually,3,9,10 but variations in study criteria and definitions prevent precise national estimates.11

Fewer data address the epidemiology of ADEs in the outpatient setting. One recent study found

an ADE rate of 3% in adult primary care outpatients,12 while an older study reported a similar

rate of 5% among ambulatory patients attending an internal medicine clinic over a 1-year

period.2

Detection and alerting interventions primarily target ADEs related to the medication

ordering process. One study of preventable inpatient ADEs in adults demonstrated that 56%

occurred at the stage of ordering.13 Among the 6.5 ADEs per 100 admissions in this study, 28%

were judged preventable, principally by changing the systems by which drugs are ordered and

administered.14 In one study of computerized ADE detection, the ADEs identified by

computerized monitoring were significantly more likely to be classified as severe than those

identified by chart review (51% vs. 42%, p=0.04).5

 Thus, monitors may capture a subset of

events with the most potential for patient injury.

Injuries due to drugs have important economic consequences. Inpatients that suffer ADEs

have increased lengths of stay of nearly 2 days and added hospital costs of more than $2000.9,15

Bootman has estimated the annual cost of drug-related morbidity and mortality within the United

States at $76.6 billion, with the majority ($47 billion) related to hospital admissions due to drug

therapy or the absence of appropriate drug therapy.16

Opportunities for Impact

Unfortunately, there are no good data as to how many hospitals have integrated lab and

medication systems, which are required for many of the triggers used in computerized ADE

monitors.

Study Designs

We found 5 studies of computerized ADE alert systems that were Level 3 or better (see

Table 8.1). Four studies17-20 detected potential ADEs using computerized monitoring and then

alerted physicians or pharmacists about the event. One additional study21 both alerted the

monitoring clinician and made recommendations for actions relating to the suspect condition.

Four studies17-20 were in the inpatient setting and one was in the ambulatory setting.21

Study Outcomes

All of the studies reported Level 1 or 2 outcomes. Level 1 outcomes were the rate of

ADEs18,19 and renal impairment (as reflected by rises in creatinine).20 Level 2 outcomes included

percent of time recommended actions were taken and time to respond to an event.17-20
81

Evidence for Effectiveness of the Practice

One study demonstrated significant decreases in adverse clinical outcomes with the alert

systems.18 This decrease included a surprisingly large reduction in allergic reactions (ones not

previously known); it is not clear how the computer alert or decision support system could have

contributed to this result.18 The second study19 showed no significant difference in the number of

adverse events in the intervention and control groups. This study and 3 others revealed

significant improvements in response times concerning lab values,17-20 and one study found a

significant decrease in the risk of serious renal impairment.20 Finally, one study demonstrated

significant changes in physician behavior/modification of therapy based on alerts with

recommended actions.21 The effect sizes shown in these studies are listed in Table 8.1.

Potential for Harm

None of the studies discuss any potential for harm associated with the monitor and alerts.

It is certainly possible that alerts could be erroneous, but it is doubtful that this would lead to any

direct patient harm. As in studies of safety in other industries, one possible source of harm could

be too many false positives. Large numbers of clinically insignificant warnings for patients

would interfere with routine care, and might result in providers ignoring all warnings, even

clinically meaningful ones.

Costs and Implementation

In general, implementation of alert monitors requires computer systems that can link

laboratory and medication information. Integrating this information requires the creation of

interface between the drug and laboratory databases, with costs that will vary depending on the

nature of the existing information systems. In addition, alert methods vary, with some

applications directly contracting physicians (which requires further integration of coverage and

pager databases) and others using pharmacist intermediaries. The cost of pharmacist review of

triggers was less than 1 FTE per hospital in 2 studies5,7; one of them reported an annual cost

savings of up to 3 million dollars by reducing preventable ADEs with this alerting technique.7

Studies thus far suggest that physicians view computerized alert systems favorably.

Forty-four percent of physician-respondents receiving alerts indicated that the alerts were helpful

and 65% wished to continue receiving them (although these alerts went to many physicians

because it was unclear who the responsible doctor was). In another study in which alerts were

sent only to the responsible physician, 95% of physician-respondents were pleased to receive

them.19

The systems in these studies were all “homegrown” and contained idiosyncrasies that

might undermine their implementation elsewhere. Clearly it is important that systems track

which physicians are responsible for which patients. In addition, all 4 of the inpatient studies

were conducted at tertiary care hospitals and the outpatient study was done at clinics affiliated

with a tertiary care center. The translation of this alerting approach to community settings may

be difficult. One community teaching hospital has reported success in detecting opportunities to

prevent injury (64/1000 admissions) using computerized detection and alerting. This report had

only a Level 4 design (no control group), so it was not included in the Table.7
82

Comment

Computerized real-time monitoring facilitates detection of actual and potential ADEs and

notification of clinicians. This in turn may aid in the prevention of ADEs or decrease the chances

that ADEs will cause harm. The monitors also yield improvements in secondary measures

relating to the length of time until response and the quality of response.

The applications in these studies were all “homegrown.” Future applications should be

evaluated and refined further. In particular, it is important to quantify the yield of collecting

these data in terms of patient outcomes, since the start-up costs are significant. If monitors do

lead to important clinical benefits, they should become standard features of commercially

available hospital computer systems. As this occurs, careful attention will need to be paid to

optimizing the response process.

In addition, little has been done to translate these monitoring systems to the outpatient

setting, largely because outpatient clinical information is often not computerized or resides in

disparate systems. As integrated computerized outpatient records become more common, the

systems developed in the inpatient setting should be translatable to the outpatient setting.
83

Table 8.1. Included studies of computerized systems for ADE detection and alerts*

Study Intervention Study Design,

Outcomes

Results†

Kuperman, 199919

Computerized alerts to physicians

via paging system

Level 1,

Level 1

Median time until initial treatment ordered:

1 vs. 1.6 hours (p=0.003)

Median time until condition resolved:

8.4 vs. 8.9 hours (p=0.11)

Number of adverse events:

no significant difference

McDonald, 197621

Alerts to outpatient physicians

with suggested responses to

medication related events

Level 1,

Level 2

Physicians performed recommended testing:

36% vs. 11% (p<0.00001)

Physicians made changes in therapy:

28% vs. 13% (p<0.026)

Evans, 199418

Computerized monitor to detect

ADEs (including drug/lab

monitors and searches of nursing

notes) and then computerized

alerts to physicians

Level 3,

Level 1

Type B ADEs (allergic or idiosyncratic)

and severe ADEs: 0.1 vs. 0.5 per 1000

patient-days (p<0.002)

Severe ADEs: 0.1 vs. 0.4 per 1000 patientdays (p<0.001)

Rind, 199420

Computerized alert system to

physicians about rising serum

creatinine values in patients

receiving potentially nephrotoxic

medications

Level 3,

Level 1

Serious renal impairment:

RR 0.45 (95% CI: 0.22-0.94)

Mean serum creatinine lower after an event

(0.16 mg/dL lower on Day 3, p<0.01)

Dose adjusted or medication discontinued

an average of 21.6 hours sooner after an

event (p<0.0001)

Bradshaw, 198917

Computerized alerts integrated

into result review and alerts by

flashing light

Level 3,

Level 2

Response time to alert condition:

3.6 (±6.5) vs. 64.6 (±67.1) hours

* ADE indicates adverse drug event; CI, confidence interval; and RR, relative risk.

† Results reported as rates with intervention vs. control (Level 1 study designs) or after

intevention vs. before intervention (Level 3 study designs).
84

References

1. Kellaway GS, McCrae E. Intensive monitoring for adverse drug effects in patients

discharged from acute medical wards. N Z Med J. 1973;78:525-528.

2. Hutchinson TA, Flegel KM, Kramer MS, Leduc DG, Kong HH. Frequency, severity and

risk factors for adverse drug reactions in adult out-patients: a prospective study. J Chronic

Dis. 1986;39:533-542.

3. Cullen DJ, Bates DW, Small SD, Cooper JB, Nemeskal AR, Leape LL. The incident

reporting system does not detect adverse drug events: a problem for quality improvement.

Jt Comm J Qual Improv. 1995;21:541-548.

4. Classen DC, Pestotnik SL, Evans RS, Burke JP. Computerized surveillance of adverse drug

events in hospital patients. JAMA. 1991;266:2847-2851.

5. Jha AK, Kuperman GJ, Teich JM, Leape L, Shea B, Rittenberg E, et al. Identifying adverse

drug events: development of a computer-based monitor and comparison with chart review

and stimulated voluntary report. J Am Med Inform Assoc. 1998;5:305-314.

6. Bowman L, Carlstedt BC, Black CD. Incidence of adverse drug reactions in adult medical

inpatients. Can J Hosp Pharm. 1994;47:209-216.

7. Raschke RA, Gollihare B, Wunderlich TA, Guidry JR, Leibowitz AI, Peirce JC, et al. A

computer alert system to prevent injury from adverse drug events: development and

evaluation in a community teaching hospital. JAMA. 1998;280:1317-20. Published erratum

appears in JAMA 1999 Feb 3;281:420.

8. Department of Health and Human Services. Health care financing administration. Fed

Regist. 1997; 62.

9. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in

hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA.

1997;277:301-306.

10. Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable

adverse drug events in hospitalized patients: a comparative study of intensive care and

general care units. Crit Care Med. 1997;25:1289-1297.

11. Adverse drug events: the magnitude of health risk is uncertain because of limited incidence

data. Washington, DC: General Accounting Office; 2000. GAO/HEHS-00-21.

12. Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, et al. Drug

complications in outpatients. J Gen Intern Med. 2000;15:149-154.

13. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse

drug events and potential adverse drug events. Implications for prevention. ADE

Prevention Study Group. JAMA. 1995;274:29-34.

14. Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan T, et al. Systems

analysis of adverse drug events. ADE Prevention Study Group. JAMA. 1995;274:35-43.

15. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of

adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study

Group. JAMA. 1997;277:307-311.

16. Johnson JA, Bootman JL. Drug-related morbidity and mortality. A cost-of-illness model.

Arch Intern Med. 1995;155:1949-1956.

17. Bradshaw KE, Gardner RM, Pryor TA. Development of a computerized laboratory alerting

system. Comput Biomed Res. 1989;22:575-587.

18. Evans RS, Pestotnik SL, Classen DC, Horn SD, Bass SB, Burke JP. Preventing adverse

drug events in hospitalized patients. Ann Pharmacother. 1994;28:523-527.
85

19. Kuperman GJ, Teich JM, Tanasijevic MJ, Ma'Luf N, Rittenberg E, Jha A, et al. Improving

response to critical laboratory results with automation: results of a randomized controlled

trial. J Am Med Inform Assoc. 1999;6:512-522.

20. Rind DM, Safran C, Phillips RS, Wang Q, Calkins DR, Delbanco TL, et al. Effect of

computer-based alerts on the treatment and outcomes of hospitalized patients. Arch Intern

Med. 1994;154:1511-1517.

21. McDonald CJ. Use of a computer to detect and respond to clinical events: its effect on

clinician behavior. Ann Intern Med. 1976;84:162-167.
86
87

Chapter 9. Protocols for High-Risk Drugs: Reducing Adverse Drug Events

Related to Anticoagulants

Tejal K. Gandhi, MD, MPH

Harvard Medical School

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

David W. Bates, MD, MSc

Harvard Medical School

Background

Published studies of adverse drug events and multiple case reports have consistently

identified certain classes of medications as particularly serious threats to patient safety.1-3 These

“high risk” medications include concentrated electrolyte solutions such as potassium chloride,

intravenous insulin, chemotherapeutic agents, intravenous opiate analgesics, and anticoagulants

such as heparin and warfarin. Analyses of some of the adverse events involving these mediations

have led to important recommendations regarding their administration. Examples include the use

of order templates for chemotherapeutic agents, removal of intravenous electrolyte solutions

from general ward stock, and protocols for reviewing the settings of intravenous pumps

delivering continuous or frequent doses of opiates.2,4,5 While these recommendations have high

face validity, they have generally not been subject to formal evaluation regarding their impact in

reducing the targeted adverse events. By contrast, several practices relating to the management

of patients receiving anticoagulants have been evaluated quite extensively, and therefore

constitute the focus of this chapter.

Heparin and warfarin are medications whose use or misuse carry significant potential for

injury. Subtherapeutic levels can lead to thromboembolic complications in patients with atrial

fibrillation or deep venous thrombosis (DVT), while supratherapeutic levels can lead to bleeding

complications. These medications are commonly involved in ADEs for a variety of reasons,

including the complexity of dosing and monitoring, patient compliance, numerous drug

interactions, and dietary interactions that can affect drug levels. Strategies to improve both the

dosing and monitoring of these high-risk drugs have potential to reduce the associated risks of

bleeding or thromboembolic events.

Practice Description

The practices reviewed in this chapter are all intended to reduce dosing and/or

monitoring errors for heparin and warfarin, as follows:

• Heparin dosing protocols (“nomograms”) typically involve a standard initial

bolus and infusion rate, instructions for when to draw the first partial

thromboplastin time (PTT), and orders for dosing adjustments in response to

this and subsequent values (so nurses can adjust doses automatically). In some

cases, the initial bolus and infusion rates are based on patient weight.

• Inpatient anticoagulation services for both heparin and warfarin (with or

without dosing nomograms) typically consist of pharmacist-run services that

provide daily pharmacy input on dosing and monitoring for patients on heparin

and/or warfarin. (We excluded studies focusing solely on warfarin prophylaxis

in orthopedic patients.6

)
88

• Outpatient anticoagulation clinics provide coordinated services for managing

outpatient warfarin therapy. Services typically include anticoagulation

monitoring and follow-up, warfarin dose adjustment, and patient education.

These clinics are usually run by pharmacists or nurses operating with physician

back-up, and sometimes following specific dosing nomograms.

• Patient self-monitoring using a home finger-stick device and self-adjustment of

warfarin dosages using a nomogram. (The accuracy of these devices and the

comparability of patients’ and professional readings have been extensively

evaluated.7-11)

Prevalence and Severity of the Target Safety Problem

Intravenous heparin and oral warfarin are commonly used medications for cardiac disease

and thromboembolism in the inpatient and outpatient settings. While in the aggregate they are

highly beneficial (see Chapter 31), these drugs can have significant morbidities unless they are

dosed and monitored appropriately. For example, inadequate therapeutic dosing of heparin can

lead to increased length of stay and the potential for clot formation and/or propagation.12 The

risk of recurrent thromboembolism is reduced if the therapeutic effect of heparin is achieved

quickly.12 In addition, Landefeld et al13 showed that the frequency of fatal, major, and minor

bleeding during heparin therapy was twice that expected without heparin therapy. The effect

with warfarin therapy was even more pronounced - approximately 5 times that expected without

warfarin therapy. Consistent with this finding, anticoagulants accounted for 4% of preventable

ADEs and 10% of potential ADEs in one large inpatient study.1

 Finally, careful drug monitoring

in hospitals can reduce ADEs, suggesting that some events are due to inadequate monitoring of

therapies and doses.14 These studies highlight the clear need for safety-related interventions with

respect to both the dosing and monitoring of these high-risk drugs in order to prevent

thromboembolic and bleeding complications.

Opportunities for Impact

The number of hospitals using weight-based heparin nomograms, or that have established

anticoagulation clinics or services is unknown. Although common in some European countries,15

patient self-management of long-term anticoagulation with warfarin is unusual in the United

States as many payers, including Medicare, do not currently cover the home testing technology.15

Study Designs

Heparin nomograms were evaluated in one randomized controlled trial (Level 1),16 one

prospective cohort comparison (Level 2)17 and 4 controlled observational studies (Level 3).18-21

Two of these studies involved weight-based nomograms.16,21 A third study involving a weightbased nomogram22 was included with the studies of anticoagulation services (see below), as

clinical pharmacists actively managed the dosing protocol. We excluded one retrospective

before-after analysis of a weight-based heparin protocol for cardiac intensive care patients,23

because the method of selecting charts for review was never stated. Moreover, when the authors

found an increase in the number of patients with excessive anticoagulation in the intervention

group, they chose a second group of control patients (again with an unspecified selection

method) for review, and in the end concluded that the difference was not significant.

All studies of outpatient anticoagulation clinics have been Level 3 studies, typically

retrospective before-after analyses,22,24-28 although one study might more appropriately be
89

regarded as a case-control study.29 A comprehensive review of the literature on various forms of

anticoagulation management30 did not meet the criteria for a systematic review, but referenced

all of the additional studies of anticoagulation clinics that we could identify31-36 and used

quantitative methods to pool their results. We use the pooled results from this article30 in Table

9.2 in place of individual entries for each of these six Level 3 studies.

Two studies evaluated the impact of a coordinated inpatient anticoagulation service

(with or without nomograms for dosing).22,37

Patient self-management of warfarin therapy has been evaluated in at least 3 randomized

controlled trials38-40 (Level 1) and one non-randomized clinical trial.41 Because a number of

higher-level studies exist, we did not include retrospective cohort analyses (Level 3) addressing

this topic.42-45

Study Outcomes

Most studies did not evaluate bleeding complications or had insufficient numbers of

patients to evaluate this outcome adequately. One recent study of an anticoagulation clinic’s

adverse events25 focused on anticoagulation as the primary outcome (Level 1), as did the review

that pooled results from 6 observational studies of anticoagulation clinics.30 As shown in Tables

9.1-3, the rest of the studies reported Level 2 outcomes, consisting of various indicators of time

to therapeutic anticoagulation and intensity or appropriateness of anticoagulation.

Evidence for Effectiveness of the Practice

• Heparin nomograms: As shown in Table 9.1, all studies showed a significant

decrease (ie, improvement) in time to achievement of a therapeutic PTT and/or

an increase in the proportion of patients in the therapeutic range.

• Inpatient anticoagulation services: As shown in Table 9.2, both Level 3 studies

evaluating this practice showed significant improvements in relevant measures

of anticoagulation.22, 37

• Outpatient anticoagulation services for warfarin (with and without dosing

nomograms): the multiple Level 3 studies of this practice showed improvements

in relevant measures of anticoagulation, with one exception.28 This study took

place in a semi-rural region of England, and the hospital-based anticoagulation

clinic was staffed mainly by junior physician trainees rotating through the

clinic. The one study that focused primarily on Level 1 outcomes25 showed

significant reductions in adverse events related to under- or overanticoagulation.

• Patient self-management: Patient self-management achieved superior measures

of anticoagulation on one Level 1 comparison with routine care.22,37 More

impressive is that two Level 1 studies38,46 and one Level 2 study41 reported

equivalent or superior measures of anticoagulation for self-management

compared with anticoagulation clinics.

Potential for Harm

Heparin nomograms are primarily intended to achieve PTT values within the therapeutic

range as quickly as possible. Although none of the studies showed increased bleeding as a result
90

of aggressive anticoagulation, it is important to note that 4 of the 6 studies showed a significant

increase in the proportion of patients with PTTs above the target range.16,19-21

Anticoagulation clinics carry the usual theoretical risk that increased fragmentation of

care will introduce new hazards, but no study showed any significant cause for concern.

Patient self-monitoring clearly carries with it risks relating to the possibilities of patient

misunderstanding of, or non-compliance with dosing and monitoring protocols. No increases in

adverse events were observed in the studies reviewed, but the patients evaluated in these studies,

even if randomized, were still chosen from a group of relatively compliant and motivated

patients.

Costs and Implementation

For anticoagulation clinics, one study showed reduced costs of $162,058 per 100 patients

annually, primarily through reductions in warfarin-related hospitalizations and emergency room

visits.25 Other studies indicate potential cost-savings due to reduced hospitalizations from

anticoagulation-related adverse events, or show that the anticoagulation was revenue

neutral.19,24,29 Considering without these offsetting potential savings, however, anticoagulant

clinics often require institutional subsidy since professional fee or laboratory payments do not

fully cover costs.

Heparin nomograms may increase lab costs due to more frequent monitoring, but one

study calculated that lab costs were offset by the need for fewer heparin boluses.22

For patient self-management of warfarin, one study showed that the cost of selfmonitoring was $11/international normalized ratio (INR) value and postulated that this would be

cost-effective if it reduced the number of clinic visits.39 Other studies have suggested that the

capillary blood testing devices themselves47 and the overall practice of patient self-management

are cost-effective.48,49 In the United States, the home monitoring devices sell for approximately

$1000. Factoring in the price of cartridges and assuming the devices operate without requiring

repair for 5 years, one source estimated an annual cost of approximately $600.40

Implementation of a heparin nonogram appears feasible, and was well received by

physicians and nurses.18 Physician/staff education about the protocols was important to its

success.23,24 One study showed a high level of physician and patient satisfaction with an

anticoagulation clinic.24 In addition, multiple studies reveal that patients who self-manage

warfarin have significantly higher levels of satisfaction and experience less anxiety.9,10,38,39
91

Comment

The primary purpose of heparin nomograms is the timely achievement of therapeutic

anticoagulation, and their superiority in this regard (compared with routine care) has been

convincingly established. While none of the studies showed adverse consequences of this focus

on timely anticoagulation, the trend toward increases in excessive anticoagulation presents safety

concerns. Studies powered to detect significant differences in bleeding complications in patients

being managed with heparin dosing protocols may be warranted.

The literature on anticoagulation clinics consists entirely of observational studies with

important possible confounders. Nonetheless, with one exception28 they are consistently shown

to achieve superior measures of anticoagulation, and in one study,25 superior clinical outcomes.

Among the practices reviewed in this chapter, the literature on patient self-management is

perhaps the most impressive. Three randomized trials and one non-randomized clinical trial

show that patient control of anticoagulation is at least equivalent, if not superior, to management

by usual care or an anticoagulation clinic. Additional observational studies reach the same

results.42-45 Thus, a relatively substantial literature supports patient self-management for

outpatient warfarin therapy for motivated patients able to comply with the monitoring and dosing

protocols. These studies clearly involved select groups of patients,9

 so that a larger randomized

trial with intention-to-treat analysis would be helpful.

Many insurance carriers in the United States, including Medicare, do not currently

subsidize the home testing technology or provide only partial coverage.15 Despite the relatively

high cost of the home testing devices, this practice may nonetheless be cost-effective due to

reduced use of other clinical services.48,49 A larger US study or detailed cost-effectiveness

analysis appears warranted, especially given the higher level of patient satisfaction with this

approach as compared with outpatient anticoagulation.
92

Table 9.1. Studies focused primarily on heparin or warfarin nomograms*

Study Study Design, Outcomes Results†

Raschke, 199316

Weight-based heparin

nomogram for patients

with venous

thromboembolism or

unstable angina

Randomized controlled trial

(Level 1)

Various markers of adequate

anticoagulation (Level 2)

PTT in therapeutic range within 24

hours: 97% vs. 77% (p<0.002)

Mean time to therapeutic PTT: 8.2 vs.

20.2 hours (p<0.001)

PTT exceeding the therapeutic range:

at 24 hours, 27% vs. 7% (p<0.001)

at 48 hours, 18% vs. 8% (p<0.001)

Elliott, 199417

Use of heparin

nomogram for patients

with acute proximal

deep venous

thrombosis

Non-randomized clinical trial

 (Level 2)

Time to therapeutic PTT

(Level 2)

Time to therapeutic PTT: less with use

of nomogram (values not given,

p=0.025)

Brown, 199721

Weight-based heparin

nomogram for ICU

patients requiring

acute anticoagulation

with unfractionated

heparin

Retrospective before-after

analysis (Level 3)

Time to therapeutic PTT

(Level 2)

Mean time to therapeutic PPT: 16 vs.

39 hours (p<0.05)

Supratherapeutic PTTs were more

common after implementation of

the nomogram, but there was no

observed increase in bleeding

Cruickshank, 199118

Heparin nomogram for

patients with acute

venous

thromboembolism

Retrospective before-after

analysis (Level 3)

Time to first therapeutic PTT,

time to correct subsequent

PTTs, time outside the

therapeutic range (Level 2)

PTT in therapeutic range at 24 hours,

66% vs. 37% (p<0.001)

PTT in therapeutic range at 48 hours,

81% vs. 58% (p<0.001)
93

Table 9.1. Studies focused primarily on heparin or warfarin nomograms* (cont.)

Study Study Design, Outcomes Results†

Hollingsworth, 199519

Heparin nomogram for

hospitalized patients

with acute venous

thromboembolism

Retrospective before-after

analysis (Level 3)

Primary outcome of the study

was length of hospital stay

(Level 3) but time to

therapeutic PTT was a

secondary outcome (Level 2)

Time to therapeutic PTT: 17.9 vs. 48.8

hours (p<0.001)

PTTs were sub-therapeutic less often:

28% vs. 56% (p<0.001)

Proportion of patients with supratherapeutic PTTs was significantly

increased in the intervention group.

There was no increase in bleeding

complications associated with this

finding, but the study was

underpowered to detect such a

difference.

Phillips, 199720

Inpatient heparin and

warfarin nomograms

and monitoring charts

Retrospective before-after

analysis (Level 3)

Measures of under- and overanticoagulation (Level 2)

Heparin nomogram

• Time spent under-anticoagulated: 

 18.5% vs, 32.7% (p<0.0001)

• Time spent above the therapeutic

range: 35.6% vs. 24.4% (p<0.01)

Warfarin nomogram:

• Time spent over-anticoagulated: 

 5.4% vs. 2.7% (p<0.001, but

questionable clinical significance)

* PTT indicates partial thromboplastin time.

† Results reported as rates with intervention vs. control (Level 1 & 2 study designs) or after

intevention vs. before intervention (Level 3 study designs).
94

Table 9.2. Inpatient anticoagulation services and outpatient anticoagulation clinics*

Study Study Design, Outcomes Results

Ansell, 199630

Pooled comparison of

anticoagulation clinics and

routine medical care

Pooled results from 6 Level

3 study designs comparing

anticoagulation clinics with

routine medical care31-36

(Level 3A)

Major bleeding and

thromboembolic events

(Level 1)

Major bleeding events per patientyear: anticoagulation clinic, 0.028

(95% CI: 0-0.069) vs. routine care,

0.109 (95% CI: 0.043-0.268)

Thromboembolic events per

patient-year: anticoagulation

clinic, 0.024 (95% CI: 0-0.08) vs.

routine care, 0.162 (95% CI:

0.062-0.486)

Hamby, 200029

Analysis of adverse events

related to outpatient

warfarin therapy among 395

patients followed at a

Veterans Affairs Hospital,

with 306 enrolled in an

anticoagulation clinic and

89 patients receiving usual

care

Case-control study

(Level 3)

Adverse events related to

under- or overanticoagulation (Level 1)

Among the 12 patients with

preventable adverse events related

to anticoagulation, 8 were not

enrolled in the anticoagulation

clinic

Patients receiving usual care had

20 times the relative risk (95% CI:

6-62) of an adverse event

compared with patients in the

anticoagulation clinic.

Lee, 199626

Comparison of pharmacistmanaged anticoagulation

clinic with patient receiving

usual care

Retrospective cohort

comparison (Level 3)

Hospital admissions related

to under- or overanticoagulation – ie,

thromboembolic or bleeding

events (Level 1)†

Patients in anticoagulation clinic

had non-significant reductions in

hospital admissions related to

thromboembolic or bleeding

events compared with control

group‡

Ellis, 199237

Pharmacy-managed

inpatient anticoagulation

service (flow sheet for

monitoring, but no

nomogram) for monitoring

patients receiving warfarin

for a variety of indications

Retrospective before-after

analysis (Level 3)

Anticoagulation “stability”

at discharge and odds of

therapeutic anticoagulation

at first outpatient visit

(Level 2)

Patients receiving the intervention

were more likely to have PT

“stability” at discharge: 61.5% vs.

42.3% (p=0.02)

Odds of having therapeutic PT at

first outpatient clinic visit with

intervention: OR 5.4 (95% CI:

1.87-15.86)
95

Table 9.2. Inpatient anticoagulation services and outpatient anticoagulation clinics* (cont.)

Study Study Design, Outcomes Results

Gaughan, 200024

Anticoagulation clinic for

outpatients receiving

warfarin for atrial

fibrillation (managed by

nurse practitioner using

warfarin dosing nomogram)

Retrospective before-after

analysis (Level 3)

Percentage of patients in the

desired range for

anticoagulation (Level 2)

was evaluated as a

secondary outcome

Minor increase in percentage of

patients with INR in desired range:

53.7% vs. 49.1% (p<0.05, but

questionable clinical significance)

Radley, 199527

Performance of pharmacistrun hospital-based

outpatient anticoagulation

clinic in England compared

with historical control

(management by rotating

physician trainees)

Retrospective before-after

analysis (Level 3)

Proportions of INR

measurements “in” or “out”

of the therapeutic range

No significant difference for

patients with stable INR in the

baseline period, but patients with

an INR result “out” of range were

more likely to return to “in” range

under anticoagulation clinic

management compared with

routine physician management

Rivey, 199322

Pharmacy-managed

inpatient anticoagulation

service (using weight-based

heparin protocol) for

medicine inpatients

compared with older fixeddose protocol without any

active management by

pharmacists

Before-after analysis 

(Level 3)

Time to therapeutic PTT

(Level 2)

Time to therapeutic PTT was less

with nomogram protocol: 40 vs.

20 hours (p<0.05)

Fewer supra-therapeutic PTTs

with protocol: 1.7 vs. 5.5 (p<0.05)

Bleeding rates: no difference but

numbers were small

* CI indicates confidence interval; INR, international normalized ratio; OR, odds ratio; PT,

prothrombin time; and PTT, partial thromboplastin time.

† We counted this outcome as Level 1, but it is important to note that authors did not capture all

of the designated clinical events, just those that resulted in admissions to the study hospital.

‡ Using the results reported in the study, we calculated the 95% CIs for admissions related to

thromboembolic events (intervention, 0.2-18.5%; usual care, 12.7-42.5%) and bleeding events

(inervention, 1.1-22.8%; usual care, 7-33.4%).
96

Table 9.3. Outpatient self-management using home testing devices and dosing

nomograms*

Study Study Design, Outcomes Results

Cromheecke, 200038

Oral anticoagulation selfmanagement with home

monitoring and dose

adjustment compared with

anticoagulation clinic

(Netherlands)

Randomized trial with

crossover comparison

(Level 1)

Adequacy of

anticoagulation (Level 2)

Percent of self-managed

measurements within 0.5 INR units of

therapeutic target did not differ (55%

vs. 49%, p=0.06). However, 29

patients (60%) during selfmanagement spent >50% of time in

target range, compared with 25 (52%)

during clinic management (p<0.05).

Sawicki, 199939

Oral anticoagulation selfmanagement with home

monitoring and dose

adjustment compared with

routine care (Germany)

Single blind, multicenter

randomized controlled

trial (Level 1)

Adequacy of

anticoagulation (Level 2)

Intervention group more often had

INRs within target range (p<0.01),

and had significantly fewer deviations

from target range and 6 months

White, 198940

Oral anticoagulation selfmanagement with home

monitoring and dose

adjustment compared with

anticoagulation clinic

(United States)

Randomized prospective

comparison (Level 1)

Adequacy of

anticoagulation (Level 2)

Self-management group had

significantly greater proportion of

patients in target INR range (93% vs.

75%, p<0.01)

Watzke, 200041

Self-management

compared with

anticoagulation clinic

(Austria)

Prospective cohort

comparison (Level 2)

Various measures of

adequacy of

anticoagulation (Level 2)

Non-significant trends towards more

INR values within the therapeutic

range for self-management group

compared with anticoagulation clinic,

both for standard therapeutic range of

INR 2.0-3.0 (82.2% vs. 68.9%) and

for more intense anticoagulation

targeted to INR range of 2.5-4.5

(86.2% vs. 80.1%)

* INR indicates international normalized ratio.
97

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20. Phillips WS, Smith J, Greaves M, Preston FE, Channer KS. An evaluation and

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21. Brown G, Dodek P. An evaluation of empiric vs. nomogram-based dosing of heparin in an

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23. Nemeth JS, Marxen TL, Piltz GW. Weight-based protocol for improving heparin therapy.

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management of atrial fibrillation and anticoagulation in a community hospital. Jt Comm J

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28. Pell JP, McIver B, Stuart P, Malone DN, Alcock J. Comparison of anticoagulant control

among patients attending general practice and a hospital anticoagulant clinic. Br J Gen

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anticoagulation self-management and management by a specialist anticoagulation clinic: a

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oral anticoagulation: a randomized controlled trial. Working Group for the Study of Patient

Self-Management of Oral Anticoagulation. JAMA. 1999; 281:145-150.

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41. Watzke HH, Forberg E, Svolba G, Jimenez-Boj E, Krinninger B. A prospective controlled

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prothrombin time monitoring after the initiation of warfarin therapy. A randomized,

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100
101

Chapter 10. Unit-Dose Drug Distribution Systems

Michael D. Murray, PharmD, MPH

Purdue University School of Pharmacy

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

Background

Medication errors are especially likely when health professionals engage in multiple

tasks within a short time span. This situation occurs repeatedly in hospitals when pharmacists

and technicians load unit-dose carts, and when nurses administer medications. Unit-dose carts

are prepared daily, often manually, by technicians and then checked by pharmacists. These carts,

containing thousands of patient-specific dosages of drugs, are sent to the wards daily, for nurses

to administer medications to patients. Dosing frequencies vary widely, ranging from regular

intervals around the clock to “stat” doses given to control acute pain or other symptoms.

Medication administration alone is an enormous task for nurses, and one in which they are

repeatedly interrupted. It is not surprising that the administration phase of medication use is

particularly vulnerable to error.1

Unit-dose dispensing of medication was developed in the 1960s to support nurses in

medication administration and reduce the waste of increasingly expensive medications. Most of

the investigations of medication errors and unit-dose dispensing took place from 1970 to 1976.

Now, unit-dose dispensing of medications is a standard of practice at hospitals in the United

States. This chapter reviews the evidence supporting this practice.

Practice Description

In unit-dose dispensing, medication is dispensed in a package that is ready to administer

to the patient.2

 It can be used for medications administered by any route, but oral, parenteral, and

respiratory routes are especially common. When unit-dose dispensing first began, hospital

pharmacies equipped themselves with machines that packaged and labeled tablets and capsules,

one pill per package. They also purchased equipment for packaging liquids in unit-doses. As the

popularity of this packaging increased, the pharmaceutical industry began prepackaging pills in

unit-of-use form. Many hospitals now purchase prepackaged unit-dose medications. However, it

is still common for hospital pharmacies to purchase bulk supplies of tablets and capsules from

manufacturers and repackage them in the central pharmacy into unit-dose packages.2

 It is

important to note that hospitals vary in the proportion of their wards covered by a unit-dose

system.

There are many variations of unit-dose dispensing. As just one example, when physicians

write orders for inpatients, these orders are sent to the central pharmacy (by pharmacists, nurses,

other personnel, or computer). Pharmacists verify these orders and technicians place drugs in

unit-dose carts. The carts have drawers in which each patient’s medications are placed by

pharmacy technicians—one drawer for each patient. The drawers are labeled with the patient’s

name, ward, room, and bed number. Before the carts are transported to the wards, pharmacists

check each drawer’s medications for accuracy. Sections of each cart containing all medication

drawers for an entire nursing unit often slide out and can be inserted into wheeled medication

carts used by nurses during their medication administration cycles. A medication administration

recording form sits on top of the cart and is used by the nurse to check-off and initial the time of

each administration of each medication. The next day, the carts are retrieved from the wards and
102

replaced by a fresh and updated medication supply. Medications that have been returned to the

central pharmacy are credited to the patient’s account.

A 1999 national survey of drug dispensing and administration practices indicated that

three-fourths of responding hospitals had centralized pharmacies, 77% of which were not

automated.2

 Larger hospitals and those affiliated with medical schools were more likely to have

some component of decentralized pharmacy services. About half of the surveyed hospitals

reported drug distribution “systems” that bypassed the pharmacy, including hospitals that

reported using floor stocks, borrowing other patients’ medications, and hidden drug supplies.

Studies often compare unit-dose dispensing to a ward stock system. In this system, nurses

order drugs in bulk supplies from the pharmacy; the drugs are stored in a medication room on the

ward. Nurses prepare medication cups for each patient during medication administration cycles.

The correct number of pills must be taken out of the correct medication container for each cycle

and taken to the patient for administration. Liquids must be poured by the nurse from the

appropriate bottle and each dose carefully measured. Nurses are responsible for any necessary

labeling. Any medications taken from stock bottles and not administered to patients are generally

disposed of.

Prevalence and Severity of the Target Safety Problem

The targets of the safety problem for unit-dosing are drug dispensing3

 and

administration.4,5 Improving these stages probably carries the greatest opportunity to reduce

medication errors.

Bates et al6

 identified 530 medical errors in 10,070 written orders for drugs (5.3

errors/100 orders) on 3 medical units observed for 51 days. Of the 530 errors, 5 (0.9%) resulted

in an adverse drug event. The most common reason for an error was a missing dose of

medication, which occurred in 53% of orders. In a systems analysis of 334 errors causing 264

adverse drug events over 6 months in 2 tertiary care hospitals, 130 errors (39%) resulted from

physician ordering, 40 (12%) involved transcription and verification, 38 (11%) reflected

problems with pharmacy dispensing, and 126 (38%) were from nursing administration.4

 In other

words, 164 (49%) of the errors in the above-cited study4

 were in the dispensing and

administration stages. In further research, the investigators found that errors resulting in

preventable adverse drug events were more than likely to be those in the administration stage

(34%) than those in the dispensing stage (4%) of the medication use process.1

Opportunities for Impact

Because unit-dose dispensing now constitutes a standard for approval by the Joint

Commission for Accreditation of Healthcare Organizations (JCAHO)7,8 and is closely linked to

the increasingly common use of automated dispensing devices (see Chapter 11), there is likely

little opportunity for further implementation of this practice in US hospitals. In a 1994 survey of

pharmacy directors, 92% of acute care hospitals reported using unit-dose dispensing.7

 Use of

unit-dose dispensing is extremely common on general medical and surgical wards, but less so in

other locations such as intensive care units, operating rooms, and emergency departments. In

these areas, bulk medication stock systems are still found. In a 1999 survey of pharmacy

directors, 80% reported that unit-dose dispensing was used for 75% or more of oral doses, and

52% of injectable medications dispensed in their hospitals.9
103

Study Designs

The 5 studies meeting inclusion criteria for this review (Table 10.1) included 4 Level 3

studies, and one prospectively designed before-after observation (Level 2 design). We excluded

the following studies for the reasons outlined:

• Read10 conducted a study of a unit-dose system applied to respiratory therapy

solutions that was focused primarily on measures of efficiency.

Volume/concentration errors in preparing respiratory solutions were also

discussed, but the method of detection was not stated nor were specific error

data provided for the study period.

• Reitberg et al11 conducted a prospective before-after study with a concurrent

comparison floor as a control (Level 2 design) in which medication errors

represented the main outcomes (Level 2). During period 1 when both wards

used the ward stock system, total errors were 4.7% on the ward that remained

on ward stock and 34.2% on the ward that used the modified dispensing

system. During period 2, the ward stock system had 5.1% error, while the

intervention ward (unit-dose) exhibited a significantly increased 18% error

rate. Excluding administration-time errors resulted in error rates of 5.1%

(conventional system) and 4.8% (unit-dose), which are not significantly

different. The greater number of errors on the modified dispensing ward

before and after the intervention were attributed by the authors to factors other

than the dispensing systems. Because of this problem, and the fact that this

study took place in a skilled nursing facility rather than an acute care hospital,

we excluded this study.

• Shultz et al12 conducted a prospective before-after study (Level 2) involving a

somewhat complicated comparison. In the baseline period, approximately

50% of wards used a unit-dose system. During the study period, some wards

switched to a unit-dose system in which nurses still administered the

medications, while other wards adopted an experimental system, in which

pharmacists and pharmacy technicians handled all aspects of the mediation

dispensing and administration process. The authors report an error rate of

0.64% for complete unit-dose plus pharmacy technician medication system

compared to 5.3% in the more conventional unit-dose system in which nurses

continue to administer medications (p<0.001 for this comparison). The

authors repeated their observations 2 years later, and show a persistent marked

reduction in the “complete unit-dose system” compared to the nurseadministered unit-dose system. Unfortunately, nowhere do the authors report

the error rate in the baseline period in the wards without a unit-dose system.

Thus, none of the results reported by the authors relate specifically to the

conversion from a multi-dose to a unit-dose system.

In addition, 2 of the relevant references identified13,14 almost certainly reported the same

data. The 2 papers have only one author in common, but they come from the same institution,

involve study wards of the same size and observation periods of the same duration, and report

identical error rates for the main comparison. The data from these 2 papers were combined to

produce a single entry in Table 10.1.
104

Lastly, we were unable to obtain one of the original studies of the unit-dose system

within the timeline of the project. The data from this study appears to have been published only

as a technical report.15 Other publications related to this study and which we were able to

obtain16-18 did not provide sufficient detail on the aspects of the study relating to medication

errors to permit abstraction or inclusion in this chapter. The published reports of a study

conducted in a private hospital similarly did not contain sufficient detail about the study methods

or results to permit abstraction and inclusion.19,20

Study Outcomes

Studies reported errors measured by direct observation using a methodology that was first

described by Barker.21 All of these studies involved Level 2 outcomes.

Evidence for Effectiveness of the Practice

Though the practice of unit-dose dispensing is generally well accepted and has been

widely implemented, the evidence for its effectiveness is modest. Most of the published studies

reported reductions in medication errors of omission and commission with unit-dose dispensing

compared with alternative dispensing systems such as ward stock systems. One exception was

the international study by Dean,22 which compared a United States hospital using unit-dose and

transcription of medication orders with a United Kingdom hospital using ward stock and no

transcription of orders. The results of this study indicated that the United Kingdom hospital had

less than half the errors of the United States hospital. The study groups were often difficult to

compare because of differing cultures, hospitals, or nursing care units. Moreover, cointerventions undoubtedly confounded the results. Each study is summarized in Table 10.1.

Potential for Harm

Unit-dosing shifts the effort and distraction of medication processing, with its potential

for harm, from the nursing ward to central pharmacy. It increases the amount of time nurses have

to do other tasks but increases the volume of work within the pharmacy. Like the nursing units,

central pharmacies have their own distractions that are often heightened by the unit-dose

dispensing process itself, and errors do occur.3

Overall, unit-dose appears to have little potential for harm. The results of most of the

Level 2 observational studies seem to indicate that it is safer than other forms of institutional

dispensing. However, the definitive study to determine the extent of harm has not yet been

conducted.

A major advantage of unit-dose dispensing is that it brings pharmacists into the

medication use process at another point to reduce error.3

 Yet, as pointed out in the Practice

Description above, about half of the hospitals in a national survey bypass pharmacy involvement

by using floor stock, borrowing patients’ medications, and hiding medication supplies.2

Costs and Implementation

The cost considerations of unit-dose dispensing are mainly a trade-off between pharmacy

and nursing personnel. The pharmacy personnel involved are mainly technicians who load unitdose ward carts for the pharmacists to check and may package some medications that are

commercially unavailable in unit-dose form. The pharmacist must verify that the correct

medication and dosage of each medication is sent to the ward for the nurse to administer.

Nursing time to maintain a drug inventory is reduced, allowing more time for other nursing

activities. A variable cost of unit-dose dispensing is the cost of equipment and supplies to those
105

hospitals that wish to do much of the packaging themselves instead of purchasing medications

pre-packaged as unit-doses.

Comment

The studies evaluating the practice of unit-dosing contain important methodologic

problems and, although yielding somewhat heterogeneous results, are overall relatively

consistent in showing a positive impact on error reduction. In contrast to other practices related

to medication use, none of the studies evaluated Level 1 outcomes, such as actual adverse drug

events. Nonetheless, unit-dose dispensing or some form of automated dispensing of unit-doses

(see Chapter 11) has become ubiquitous in American hospitals and a standard of care in the

delivery of pharmacy services. Consequently, it is unlikely that more rigorous studies could now

be conducted.
106

Table 10.1. Studies evaluating the impact of unit-dose dispensing on medication errors*

Study Study Design, Outcomes† Results: Error Rates (95% CI)

Hynniman,

197023

Cross-sectional comparison between

study hospital and non-randomly

selected “comparison” hospitals (Level

3)

Errors of commission and omission

(Level 2) among doses ordered

Unit-dose system: 3.5% (3.1-4.0%)

Conventional distribution systems at 4 hospitals:

8.3% (7.1-9.7%)

9.9% (8.0-12.2%)

11.4% (9.9-13.2%)

20.6% (18.4-22.9%)

Means,

197513

Simborg,

197514‡

Cross-sectional comparison of 2 wards

within a single hospital over a 60-day

period (Level 3)

Errors of commission (Level 2) among

doses administered during randomly

chosen observation periods

Unit-dose ward: 1.6% (1.0-2.5%)

Multi-dose ward: 7.4% (6.1-8.9%)§

Schnell,

197624

Prospective before-after study (Level

2) at four Canadian hospitals

Errors observed during medication

preparation and administration (Level

2)

Before vs. after implementation of unit-dose

system: 37.2 vs. 38.5%;

42.9 vs. 23.3%;

20.1% vs. 7.8%;

38.5% vs. 23.1%¶

Dean,

199522

Cross-sectional comparison (Level 3) of

US and UK hospitals with different

pharmacy distribution systems

Errors observed during medication

administration (Level 2)

84 errors among 2756 observations in UK

hospital using traditional ward stock system:

3.0% (2.4-3.7%)

63 errors among 919 observations in US hospital

using unit-doses and automated dispensing: 6.9%

(5.2-8.5%)

Absolute difference: 3.9% (2.1-5.7%)

Taxis,

199825

Cross-sectional comparison (Level 3) of

2 hospitals in Germany and one hospital

in the UK

Errors observed during medication

administration

UK hospital using traditional ward stock system:

8.0% (6.2-9.8%)

German hospital using traditional ward stock

system: 5.1% (4.4-5.8)

German hospital using unit-dose system: 2.4%

(2.0-2.8%)

Omission was the most common type of error

* CI indicates confidence interval.

† Errors of commission include administration of wrong dose or wrong or unordered drug, whereas errors

of omission include missed doses for inclusion in a patient’s unit-dose drawer or a dose not

administered.

‡ As outlined in the text, the similarities in study setting, time, design and results suggest that these 2

references contain data from the same study; information from these references was therefore combined

and treated as a single study.

§ The 95% CIs shown in the table were calculated using the reported data: 20 errors in 1234 observed

doses on the unit-dose ward vs. 105 errors in 1428 observed doses on the multidose ward.
107

¶ When wrong time errors were omitted, the above results changed so that the change to a unit-dose was

associated with a significant increase in errors at the first hospital, a non-significant decrease in errors at

the second hospital, and significant decreases in errors at the other two hospitals.
108

References

1. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse

drug events and potential adverse drug events: Implications for prevention. JAMA.

1995;274:29-34.

2. Ringold DJ, Santell JP, Schneider PJ, Arenberg S. ASHP national survey of pharmacy

practice in acute care settings: prescribing and transcribing–1998. American Society of

Health-System Pharmacists. Am J Health Syst Pharm. 1999;56:142-157.

3. Facchinetti NJ, Campbell GM, Jones DP. Evaluating dispensing error detection rates in a

hospital pharmacy. Med Care. 1999;37:39-43.

4. Leape L, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan T, et al. Systems

analysis of adverse drug events. JAMA. 1995;274:35-43.

5. Tissot E, Cornette C, Demoly P, Jacquet M, Barale F, Capellier G. Medication errors at the

administration stage in an intensive care unit. Intensive Care Med. 1999;25:353-359.

6. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between

medication errors and adverse drug events. J Gen Intern Med. 1995;10:199-205.

7. Santell JP. ASHP national survey of hospital-based pharmaceutical services–1994. Am J

Health Syst Pharm. 1995;52:1179-1198.

8. Godwin HN, Scott BE. Institutional patient care. In: Gennaro AR, editor. Remington: The

Science and Practice of Pharmacy. Baltimore: Lippincott Williams & Wilkins; 2000:1911-

31.

9. Ringold DJ, Santell JP, Schneider PJ. ASHP national survey of pharmacy practice in acute

care settings: dispensing and administration–1999. Am J Health Syst Pharm.

2000;57:1759-1775.

10. Read OK. Unit dose packaging of respiratory therapy solutions. Am J Health Syst Pharm.

1975;32:49-51.

11. Reitberg DP, Miller RJ, Bennes JF. Evaluation of two concurrent drug-delivery systems in

a skilled-nursing facility. Am J Health Syst Pharm. 1982;39:1316-1320.

12. Shultz SM, White SJ, Latiolais CJ. Medication errors reduced by unit-dose. Hospitals.

1973;47:107-112.

13. Means BJ, Derewicz HJ, Lamy PP. Medication errors in a multidose and computer-based

unit dose drug distribution system. Am J Hosp Pharm. 1975;32:186-191.

14. Simborg DW, Derewicz HJ. A highly automated hospital medication system: Five year's

experience and evaluation. Ann Intern Med. 1975;83:342-346.

15. A study of patient care involving a unit dose system. Final report: University of Iowa;

1966. U.S.P.H.S. Grant # HM-00328-01.

16. Greth PA, Tester WW, Black HJ. Decentralized pharmacy operations utilizing the unit

dose concept. II. Drug information services and utilization in a decentralized pharmacy

substation. Am J Hosp Pharm. 1965;22:558-563.

17. Black HJ, Tester WW. Decentralized pharmacy operations utilizing the unit dose concept.

3. Am J Hosp Pharm. 1967;24:120-129.

18. Black HJ, Tester WW. The unit dose drug-distribution system. J Iowa Med Soc.

1968;58:1174-1176.

19. Slater WE, Hripko JR. The unit-dose system in a private hospital. 1. Implementation. Am J

Hosp Pharm. 1968;25:408-417.

20. Slater WE, Hripko JR. The unit-dose system in a private hospital. II. Evaluation. Am J

Hosp Pharm. 1968;25:641-648.
109

21. Barker KN, McConnell WE. The problems of detecting medication errors in hospitals. Am

J Hosp Pharm. 1962;19:361-369.

22. Dean BS, Allan EL, Barber ND, Barker KN. Comparison of medication errors in an

American and British hospital. Am J Health Syst Pharm. 1995;52:2543-2549.

23. Hynniman CE, Conrad WF, Urch WA, Rudnick BR, Parker PF. A comparison of

medication errors under the University of Kentucky unit dose system and traditional drug

distribution systems in four hospitals. Am J Hosp Pharm. 1970;27:803-814.

24. Schnell BR. A study of unit-dose drug distribution in four Canandian hospitals. Can J

Hosp Pharm. 1976;29:85-90.

25. Taxis K, Dean B, Barber N. Hospital drug distribution systems in the UK and Germany - a

study of medication errors. Pharm World Sci. 1998;21:25-31.
110
111

Chapter 11. Automated Medication Dispensing Devices

Michael D. Murray, PharmD, MPH

Purdue University School of Pharmacy

Background

In the 1980s, automated dispensing devices appeared on the scene, a generation after the

advent of unit-dose dispensing (Chapter 11). The invention and production of these devices

brought hopes of reduced rates of medication errors, increased efficiency for pharmacy and

nursing staff, ready availability of medications where they are most often used (the nursing unit

or inpatient ward), and improved pharmacy inventory and billing functions.1-4 Although the

capacity of such systems to contribute to patient safety appears great, surprisingly few studies

have evaluated the clinical impact of these devices.

Practice Description

Automated dispensing systems are drug storage devices or cabinets that electronically

dispense medications in a controlled fashion and track medication use. Their principal advantage

lies in permitting nurses to obtain medications for inpatients at the point of use. Most systems

require user identifiers and passwords, and internal electronic devices track nurses accessing the

system, track the patients for whom medications are administered, and provide usage data to the

hospital’s financial office for the patients’ bills.

These automated dispensing systems can be stocked by centralized or decentralized

pharmacies. Centralized pharmacies prepare and distribute medications from a central location

within the hospital. Decentralized pharmacies reside on nursing units or wards, with a single

decentralized pharmacy often serving several units or wards. These decentralized pharmacies

usually receive their medication stock and supplies from the hospital’s central pharmacy.

More advanced systems provide additional information support aimed at enhancing

patient safety through integration into other external systems, databases, and the Internet. Some

models use machine-readable code for medication dispensing and administration. Three types of

automated dispensing devices were analyzed in the studies reviewed here, the McLaughlin

dispensing system, the Baxter ATC-212 dispensing system, and the Pyxis Medstation Rx. Their

attributes are described below.

• The McLaughlin dispensing system5

 includes a bedside dispenser, a

programmable magnetic card, and a pharmacy computer. It is a locked system

that is loaded with the medications prescribed for a patient. At the appropriate

dosing time, the bedside dispenser drawer unlocks automatically to allow a

dose to be removed and administered. A light above the patient’s door

illuminates at the appropriate dosing time. Only certain medications fit in the

compartmentalized cabinet (such as tablets, capsules, small pre-filled

syringes, and ophthalmic drops).

• The Baxter ATC-212 dispensing system 6

 uses a microcomputer to pack unitdose tablets and capsules for oral administration. It is usually installed at the

pharmacy. Medications are stored in calibrated canisters that are designed

specifically for each medication. Canisters are assigned a numbered location,

which is thought to reduce mix-up errors upon dispensing. When an order is

sent to the microcomputer, a tablet is dispensed from a particular canister. The
112

drug is ejected into a strip-packing device where it is labeled and hermetically

sealed.

• The Pyxis Medstation, Medstation Rx, and Medstation Rx 1000 are automated

dispensing devices kept on the nursing unit.7-9 These machines are often

compared to automatic teller machines (ATMs). The Medstation interfaces

with the pharmacy computer. Physicians’ orders are entered into the pharmacy

computer and then transferred to the Medstation where patient profiles are

displayed to the nurse who accesses the medications for verified orders. Each

nurse is provided with a password that must be used to access the Medstation.

Pharmacists or technicians keep these units loaded with medication. Charges

are made automatically for drugs dispensed by the unit. Earlier models had

sufficient memory to contain data for about one week, and newer models can

store data for longer periods.

Studies reviewed did not include the automated dispensing systems manufactured by

Omnicell, which produces point-of-use systems that can be integrated into a hospital’s

information system.10 Omnicell systems are also capable of being integrated into external

support systems that support machine-readable code, drug information services, and medication

error reporting systems.

Prevalence and Severity of the Target Safety Problem

Medication errors within hospitals occur with 2% to 17% of doses ordered for

inpatients.5,7,11-14 It has been suggested that the rate of inpatient medication errors is one per

patient per inpatient day.15 The specific medication errors targeted by automated dispensing

systems are those related to drug dispensing and administration. Even with the use of unit-doses

(see Chapter 11) errors still occur at the dispensing16 and administration stages3,17 of the

medication use process. For instance, in one large study of 530 medical errors in 10,070 written

orders for drugs (5.3 errors/100 orders),18 pharmacy dispensing accounted for 11% of errors and

nursing administration 38%.3

Opportunities for Impact

Automated dispensing devices have become increasingly common either to supplement

or replace unit-dose distribution systems in an attempt to improve medication availability,

increase the efficiency of drug dispensing and billing, and reduce errors. A 1999 national survey

of drug dispensing and administration practices indicated that 38% of responding hospitals used

automated medication dispensing units and 8.2% used machine-readable coding with

dispensing.19 Three-fourths of respondents stated that their pharmacy was centralized and of

these centralized pharmacies, 77% were not automated. Hospitals with automated centralized

pharmacies reported that greater than 50% of their inpatient doses were dispensed via centralized

automated systems. Half of all responding hospitals used a decentralized medication storage

system. One-third of hospitals with automated storage and dispensing systems were linked to the

pharmacy computer. Importantly, about half of the surveyed hospitals reported drug distributions

that bypassed the pharmacy including floor stock, borrowing patients’ medications, and hidden

drug supplies.

Study Designs

There were no true randomized trials. One crossover study of the McLaughlin dispensing

system randomized nurses to work with the intervention medication system or the control
113

system.5

 We classified this as a Level 2 study, since, from the patient perspective, the design is

that of a non-randomized trial. Other studies included in this review consisted of retrospective

observational studies with before-after6-8 or cross-sectional design11 (Level 3). The reviewed

studies described dispensing systems for orally administered medications, and were published

between 1984 and 1995 (see Table 12.1).

Study Outcomes

All studies measured rates of medication errors (Level 2 outcome). Four studies5,7,8,11

detected errors by direct observation using a methodology that was first described by Barker.5

Direct observation methods have been criticized because of purported Hawthorne effect (bias

involving changed behavior resulting from measurements requiring direct observation of study

subjects). However, proponents of the method state that such effects are short-lived, dissipating

within hours of observation.15 Dean and Barber have recently demonstrated the validity and

reliability of direct observational methods to detect medication administration errors.20 Another

study, a Level 3 design, determined errors by inspecting dispensed drugs.6

Evidence for Effectiveness of the Practice

The evidence provided by the limited number of available, generally poor quality studies

does not suggest that automated dispensing devices reduce medication errors. There is also no

evidence to suggest that outcomes are improved with the use of these devices. Most of the

published studies comparing automated devices with unit-dose dispensing systems report

reductions in medication errors of omission and scheduling errors with the former.7,9 The studies

suffer from multiple problems with confounding, as they often compare hospitals or nursing care

units that may differ in important respects other than the medication distribution system.

Potential for Harm

Human intervention may prevent these systems from functioning as designed.

Pharmacists and nurses can override some of the patient safety features. When the turn around

time for order entry into the automated system is prolonged, nurses may override the system

thereby defeating its purpose. Furthermore, the automated dispensing systems must be refilled

intermittently to replenish exhausted supplies. Errors can occur during the course of refilling

these units or medications may shift from one drawer or compartment to another causing

medication mix-ups. Either of these situations can slip past the nurse at medication

administration.

The results of the study of the McLaughlin dispensing system indicated that though

overall errors were reduced compared to unit-dose (10.6% vs. 15.9%), errors decreased for 13 of

20 nurses but increased for the other 7 nurses.5

 In a study of Medstation Rx vs. unit-dose,8 errors

decreased in the cardiovascular surgery unit, where errors were recorded by work measurement

observations. However, errors increased over 30% in 6 of 7 nurses after automated dispensing

was installed in the cardiovascular intensive care unit, where incident reports and medication

error reports were both used for ascertaining errors, raising the question of measurement bias.

Finally, in a study primarily aimed at determining differences in errors for ward and unit-dose

dispensing systems,11 a greater error prevalence was found for medications dispensed using

Medstation Rx compared with those dispensed using unit-dose or non-automated floor stock

(17.1% vs. 5.4%).
114

Costs and Implementation

The cost of automated dispensing mainly involves the capital investment of renting or

purchasing equipment for dispensing, labeling, and tracking (which often is done by computer).

A 1995 study revealed that the cost of Medstation Rx to cover 10 acute care units (330 total

beds) and 4 critical care units (48 total beds) in a large referral hospital would be $1.28 million

over 5 years. Taking into account costs saved from reduced personnel and decreased drug waste,

the units had the potential to save $1 million over 5 years. Most studies that examine economic

impact found a trade-off between reductions in medication dispensing time for pharmacy and

medication administration time for nursing personnel. A common complaint by nurses is long

waiting lines at Pyxis Medstations if there are not enough machines. Nurses must access these

machines using a nurse-specific password. This limited access to drugs on nursing units

decreases drug waste and pilferage.

Comment

Although the implementation of automated dispensing reduces personnel time for

medication administration and improves billing efficiency, reduction in medication errors have

not been uniformly realized. Indeed, some studies suggest that errors may increase with some

forms of automation. The results of the study of the McLaughlin Dispensing System by Barker et

al5

 showed considerable nurse-to-nurse variability in the error rate between the automated

system and conventional unit dose. Qualitative data aimed at determining the reason for this

variability would be useful. The study by Klein et al6

 indicated little difference in the accuracy of

medication cart filling by the Baxter ATC-212 (0.65%) versus filling by technicians (0.84%).

Borel and Rascati found that medication errors, largely those related to the time of

administration, were fewer after implementation of the Pyxis Medstation Rx (10.4%) compared

with the historical period (16.9%).7

 These results are consistent with a more recent study by

Shirley, that found a 31% increase in the on-time administration of scheduled doses after

installation of the Medstation Rx 1000.9

 In contrast, errors were greater after Medstation Rx in

the study by Schwarz and Brodowy,8

 increasing on 6 of 7 nursing units by more than 30%.

Finally, Dean et al found half the errors in a ward-based system without automation in the

United Kingdom (3.0%, 95% CI: 2.4-3.7%) compared with an automated unit-dose medication

distribution system in the United States (6.9%, 95% CI: 5.2-8.5%).11

The practical limitations of the systems were illustrated by a variety of process deviations

observed by Borel and Rascati.7

 These included nurses waiting at busy administration times,

removal of doses ahead of time to circumvent waiting, and overriding the device when a dose

was needed quickly. These procedural failures emphasize an often-raised point with the

introduction of new technologies, namely that the latest innovations are not a solution for

inadequate or faulty processes or procedures.2

Although automated dispensing systems are increasingly common, it appears they may

not be completely beneficial in their current form. Further study is needed to demonstrate the

effectiveness of newer systems such as the Omnicell automated dispensing devices. If the

standard, namely unit-dose dispensing, is to be improved, such improvements will likely derive

from robotics and informatics. To document impact of automated dispensing devices on patient

safety, studies are needed comparing unit-dose dispensing with automated dispensing devices.

Until the benefits of automated dispensing devices become clearer, the opportunities for impact

of these devices is uncertain.
115

Table 11.1. Six studies reviewing automated drug dispensing systems*

Study Study Design Study Outcomes N Results

Barker,

19845

Prospective

controlled

clinical trial

(Level 2)

Errors of omission and

commission among

number of ordered and

unauthorized doses.

(Level 2)

1775 96 errors among 902 observations

(10.6%) using the McLaughlin

dispensing system vs. 139 errors

among 873 observations (15.9%)

using unit-dose dispensing (control)

Klein,

19946

Prospective

comparison of

two cohorts

(Level 2)

Dispensing errors in

unit-dose drawers to be

delivered to nursing

units (Level 2)

7842 34 errors found among 4029 doses

(0.84%) filled manually by

technicians vs. 25 errors among 3813

doses (0.66%) filled by automated

dispensing device

Borel,

19957

Prospective

before-after study

(Level 2)

Errors observed during

medication

administrationin

medications

administered (Level 2)

1802 148 errors among 873 observations

(16.9%) before vs. 97 errors among

929 observations (10.4%) after

Medstation Rx (p<0.001). Most errors

were wrong time errors.

Schwarz,

19958

Prospective

before-after study

(Level 2)

Errors in medications

administered (Level 2)

NA† Medication errors decreased after

automated dispensing on the

cardiovascular surgery unit but

increased on the cardiovascular

intensive care unit.

Dean,

199511

Cross-sectional

comparison

(Level 3) of US

and UK hospitals

with different

pharmacy

distribution

systems

Errors in medications

administered (Level 2)

3675 63 errors among 919 observations

(6.9%, 95% CI: 5.2-8.5%) in the US

hospital using unit doses and

automated dispensing vs. 84 errors

among 2756 observations (3.0%; 95%

CI, 2.4-3.7%) in the UK hospital

using ward stock. The absolute

difference in error rates was 3.9%

(95%CI: 2.1-5.7%).

* CI indicates confidence interval.

† Study used various denominator data.
116

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2. Murray MD. Information technology: the infrastructure for improvements to the

medication-use process. Am J Health Syst Pharm. 2000;57:565-571.

3. Guerrero RM, Nickman NA, Jorgenson JA. Work activities before and after

implementation of an automated dispensing system. Am J Health Syst Pharm.

1996;53:548-554.

4. Felkey BG, Barker KN. Technology and automation in pharmaceutical care. J Am Pharm

Assoc (Wash). 1996;NS36:309-314.

5. Barker KN, Pearson RE, Hepler CD, Smith WE, Pappas CA. Effect of an automated

bedside dispensing machine on medication errors. Am J Hosp Pharm. 1984;41:1352-1358.

6. Klein EG, Santora JA, Pascale PM, Kitrenos JG. Medication cart-filling time, accuracy,

and cost with an automated dispensing system. Am J Hosp Pharm. 1994;51:1193-1196.

7. Borel JM, Rascati KL. Effect of an automated, nursing unit-based drug-dispensing device

on medication errors . Am J Health Syst Pharm. 1995;52:1875-1879.

8. Schwarz HO, Brodowy BA. Implementation and evaluation of an automated dispensing

system. Am J Health Syst Pharm. 1995;52:823-828.

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10. Omnicell Automated Systems. Omnicell Homepage. Available at:

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American and British hospital. Am J Health Syst Pharm. 1995;52:2543-2549.

12. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse

drug events and potential adverse drug events: Implications for prevention. JAMA.

1995;274:29-34.

13. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in

hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA.

1997;277:301-306.

14. Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable

adverse drug events in hospitalized patients: a comparative study of intensive care and

general care units. Crit Care Med. 1997;25:1289-1297.

15. Allan EL, Barker KN. Fundamentals of medication error research. Am J Hosp Pharm.

1990;47:555-571.

16. Facchinetti NJ, Campbell GM, Jones DP. Evaluating dispensing error detection rates in a

hospital pharmacy. Med Care. 1999;37:39-43.

17. Tissot E, Cornette C, Demoly P, Jacquet M, Barale F, Capellier G. Medication errors at the

administration stage in an intensive care unit. Intensive Care Med. 1999;25:353-3359.

18. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between

medication errors and adverse drug events. J Gen Intern Med. 1995;10:199-205.

19. Ringold DJ, Santell JP, Schneider PJ. ASHP national survey of pharmacy practice in acute

care settings: dispensing and administration–1999. Am J Health Syst Pharm.

2000;57:1759-1775.

20. Dean B, Barber N. Validity and reliability of observational methods for studying

medication administration errors. Am J Health Syst Pharm. 2001;58:54-59.
117
118

Section B. Infection Control

Chapter 12. Practices to Improve Handwashing Compliance

Chapter 13. Impact of Barrier Precautions in Reducing the Transmission of Serious

Nosocomial Infections

Chapter 14. Impact of Changes in Antibiotic Use Practices on Nosocomial Infections and

Antimicrobial Resistance – Clostridium Difficile and Vancomycin-resistant

Enterococcus (VRE)

Chapter 15. Prevention of Nosocomial Urinary Tract Infections

Subchapter 15.1. Use of Silver Alloy Urinary Catheters

Subchapter 15.2. Use of Suprapubic Catheters

Chapter 16. Prevention of Intravascular Catheter-Associated Infections

Subchapter 16.1. Use of Maximum Barrier Precautions during Central Venous

Catheter Insertion

Subchapter 16.2. Use of Central Venous Catheters Coated with Antibacterial or

Antiseptic Agents

Subchapter 16.3. Use of Chlorhexidine Gluconate at the Central Venous

Catheter Insertion Site

Subchapter 16.4. Other Practices

Chapter 17. Prevention of Ventilator-Associated Pneumonia (VAP)

Subchapter 17.1. Patient Positioning: Semi-recumbent Positioning and

Continuous Oscillation

Subchapter 17.2. Continuous Aspiration of Subglottic Secretions

Subchapter 17.3. Selective Digestive Tract Decontamination

Subchapter 17.4. Sucralfate and Prevention of VAP
119

Chapter 12. Practices to Improve Handwashing Compliance

Ebbing Lautenbach, MD, MPH, MSCE

University of Pennsylvania School of Medicine

Background

Hospital-acquired infections exact a tremendous toll, resulting in increased morbidity and

mortality, and increased health care costs.1,2 Since most hospital-acquired pathogens are

transmitted from patient to patient via the hands of health care workers,3

 handwashing is the

simplest and most effective, proven method to reduce the incidence of nosocomial infections.4

Indeed, over 150 years ago, Ignaz Semmelweis demonstrated that infection-related mortality

could be reduced when health care personnel washed their hands.5

 A recent review summarized

the 7 studies published between 1977 and 1995 that examined the relationship between hand

hygiene and nosocomial infections.6

Most of the reports analyzed in this study reveal a temporal relation between improved

hand hygiene and reduced infection rates.6

 Despite this well-established relationship, compliance

with handwashing among all types of health care workers remains poor.7-11 Identifying effective

methods to improve the practice of handwashing would greatly enhance the care of patients and

result in a significant decrease in hospital-acquired infections.

Practice Description

This chapter focuses on practices that increase compliance with handwashing, rather than

the already proven efficacy of handwashing itself.4

 The term “handwashing” defines several

actions designed to decrease hand colonization with transient microbiological flora, achieved

either through standard handwashing or hand disinfection.4

 Standard handwashing refers to the

action of washing hands in water with detergent to remove dirt and loose, transient flora. Hand

disinfection refers to any action where an antiseptic solution is used to clean the hands (ie,

medicated soap or alcohol). Handwashing with bland soap (without disinfectant) is inferior to

handwashing with a disinfecting agent.12 Hygienic hand rub consists of rubbing hands with a

small quantity (2-3mL) of a highly effective and fast acting antiseptic agent. Because alcohols

have excellent antimicrobial properties and the most rapid action of all antiseptics, they are the

preferred agents for hygienic hand rub (also called waterless hand disinfection). Also, alcohols

dry very rapidly, allowing for faster hand disinfection.4

Given health care workers’ documented low compliance with recommended

handwashing practices,7-9 improving compliance represents a more pressing patient safety

concern than does the choice of different disinfectants, or attention to other specific issues such

as choice of drying method, removal of rings, etc. Of the 14 studies reviewed in this chapter

(Table 12.1), all study sites utilized hygienic hand rub and/or another method of hand

disinfection as standard practice. However, only 2 studies assessed the specific characteristics of

handwashing practice (eg, duration of washing, method of drying) according to established

hospital guidelines,13,14 while the other 12 studies assessed only whether or not handwashing

occurred after patient contact.
120

Prevalence and Severity of the Target Safety Problem

Nosocomial infections occur in about 7-10% of hospitalized patients1

 and account for

approximately 80,000 deaths per year in the United States.15 Although handwashing has been

proven to be the single most effective method to reduce nosocomial infections, compliance with

recommended hand hygiene practices is unacceptably low.7-9 Indeed, a recent review of 11

studies noted that the level of compliance with basic handwashing ranged from 16% to 81%.4

 Of

these 11 studies, only 2 noted compliance levels above 50%.4

 One reason for poor handwashing

compliance may be that the importance of this simple protocol for decreasing infections is

routinely underestimated by health care workers.2

 Recent surveys demonstrate that although

most health care workers recognize the importance of handwashing in reducing infections, they

routinely overestimate their own compliance with this procedure.10 A survey of approximately

200 health care workers noted that 89% recognized handwashing as an important means of

preventing infection.10 Furthermore, 64% believed they washed their hands as often as their

peers, and only 2% believed that they washed less often than their peers did.10

Opportunities for Impact

Given these findings, opportunities for improvement in current practice are substantial,

and efforts to improve current practice would have vast applicability. Many risk factors for noncompliance with hand hygiene guidelines have been identified, including professional category

(eg, physician, nurse, technician), hospital ward, time of day or week, and type and intensity of

patient care.8

 These results suggest that interventions could be particularly targeted to certain

groups of health care workers or to particular locations, to increase the likelihood of compliance.

Importantly, this study demonstrates that the individuals with the highest need for hand hygiene

(ie, those with the greatest workloads) were precisely the same group least likely to wash their

hands. Finally, another recent study noted that approximately 75% of health care workers

surveyed reported that rewards or punishments would not improve handwashing, but 80%

reported that easy access to sinks and availability of hand washing facilities would lead to

increased compliance.10

Study Designs

A structured search of the PubMed database (including MEDLINE) and review of the

bibliographies of relevant articles identified 14 studies that have examined methods to improve

handwashing compliance (Table 12.1). Three studies were non-randomized controlled trials

(Level 2) that directly compared separate units, or parts of units, in which one area received the

intervention and another did not.14,16,17 Eleven studies were before-after studies (Level 3), in

which baseline data regarding handwashing rates were obtained during an initial observation

period, and then measured again in the time period after a particular intervention. Regardless of

the type of study design, details regarding the comparability of the groups under observation

were reported in only 4 studies.13,16,18,19

Study Outcomes

All of the studies reported changes in percent compliance with handwashing, assessing

whether or not handwashing took place (Table 12.1). While 13 studies assessed handwashing

through observation of health care worker behavior (Level 2), one study assessed soap usage as

an indicator of handwashing frequency (Level 3).20 Two studies also assessed changes in the

quality of handwashing.13,14 Several studies reported results of surveys conducted following
121

interventions to assess effectiveness and potential adverse events related to the

interventions.14,20,21 One study also assessed changes in 2 clinical outcomes (incidence of

nosocomial infections and newly detected cases of methicillin-resistant Staphylococcus aureus)

as a result of interventions (Level 1).18

Evidence for Effectiveness of the Practice

Since many different risk factors have been identified for non-compliance with

handwashing, it is not surprising that a variety of different interventions have been studied in an

effort to improve this practice. While most of the reviewed studies demonstrated significant

improvement in handwashing compliance,9,13,17,18,20-22 some did not.14,19,23,24 No single strategy

has consistently been shown to sustain improved compliance with handwashing protocols.11 In

fact, of the studies which assessed longer-term results following intervention,16,21,25 all 3 found

that compliance rates decreased from those immediately following the intervention, often

approaching pre-intervention levels.

Potential for Harm

While no harm is likely to befall a patient as a result of handwashing, one potential

adverse effect of handwashing for health care workers is skin irritation. Indeed, skin irritation

constitutes an important barrier to appropriate compliance with handwashing guidelines.27 Soaps

and detergents can damage the skin when applied on a regular basis. Alcohol-based preparations

are less irritating to the skin, and with the addition of emollients, may be tolerated better.6

Another potential harm of increasing compliance with handwashing is the amount of time

required to do it adequately. Current recommendations for standard handwashing suggest 15-30

seconds of handwashing is necessary for adequate hand hygiene.28 Given the many times during

a nursing shift that handwashing should occur, this is a significant time commitment that could

potentially impede the performance of other patient care duties. In fact, lack of time is one of the

most common reasons cited for failure to wash hands.11 Since alcohol-based handrubs require

much less time, it has been suggested that they might resolve this concern. In fact, a recent study

which modeled compliance time for handwashing as compared with alcoholic rubs, suggested

that, given 100% compliance, handwashing would consume 16 hours of nursing time per

standard day shift, while alcohol rub would consume only 3 hours.29

Costs and Implementation

Interventions designed to improve handwashing may require significant financial and

human resources. This is true both for multifaceted educational/feedback initiatives, as well as

for interventions that require capital investments in equipment such as more sinks, automated

sinks, or new types of hand hygiene products. The costs incurred by such interventions must be

balanced against the potential gain derived from reduced numbers of nosocomial infections.

Only one study addressed the cost implications of handwashing initiatives.20 The implementation

of a patient education campaign, when compared to the estimated $5000 per episode cost of each

nosocomial infection, would result in an annual savings of approximately $57,600 for a 300-bed

hospital with 10,000 admissions annually.20 As others have estimated that the attributable cost of

a single nosocomial bloodstream infection is approximately $40,000 per survivor,30 the potential

cost savings of interventions to improve handwashing may be even greater.
122

Comment

While many studies have investigated a variety of interventions designed to improve

compliance with handwashing, the results have been mixed. Even when initial improvements in

compliance have been promising, long-term continued compliance has been disappointing.

Future studies should focus on more clearly identifying risk factors for non-compliance, and

designing interventions geared toward sustainability. Some investigators postulate that better

understanding of behavior theory, and its application to infection control practices, might result

in more effectively designed interventions.26 In addition, any intervention must target reasons for

non-compliance at all levels of health care (ie, individual, group, institution) in order to be

effective. A more detailed study of the cost (and potentially cost savings) of handwashing

initiatives would also foster greater enthusiasm among health care institutions to support such

initiatives.
123

Table 12.1. Fourteen studies of practices to improve handwashing compliance*

Study Setting; Practice Study Design,

Outcomes

Handwashing Compliance

(unless otherwise noted)†

All medical staff in a neurologic ICU and a surgical

ICU in a 350-bed tertiary care teaching hospital in

Washington, DC, 1983-84; multifaceted intervention

(education, automatic sinks, feedback)16

Level 2, Level

2

69% vs. 59% (p=0.005)

Medical staff in 2 ICUs in a university teach hospital in

Philadelphia; increase number of available sinks17

Level 2, Level

2

76% vs. 51% (p<0.01)

Medical staff in a 6-bed post-anesthesia recovery room

and a 15-bed neonatal ICU in a tertiary care hospital in

Baltimore, 1990; automatic sink compared with

standard sink14

Level 2, Level

2

Mean handwashes per hour:

1.69 vs. 1.21 on unit 1; 2.11

vs. 0.85 on unit 2; (p<0.001)

All staff at a large acute-care teaching hospital in

France, 1994-97; hand hygiene campaign including

posters, feedback, and introduction of alcohol-based

solution18

Level 3, Level

1

Noscomial infections: 16.9%

vs. 9.9% Handwashing:

66.2% vs. 47.6% (p<0.001)

Medical staff in a 6-bed pediatric ICU in a large

academic medical center in Virginia, 1982-83;

mandatory gowning19

Level 3, Level

2

29.6% vs. 30.7%

Medical staff in 2 ICUs in a community teaching

hospital in Tennessee, 1983-84; sequential

interventions of lectures, buttons, observation, and

feedback24

Level 3, Level

2

29.9% vs. 22% (p=0.071)

Medical staff in an 18-bed ICU in a tertiary care

hospital in Australia; introduction of chlorhexidinebased antiseptic handrub lotion9

Level 3, Level

2

45% vs. 32% (p<0.001)

12 nurses in a 12-bed ICU in Mississippi, 1990;

education/feedback intervention31

Level 3, Level

2

92% vs. 81%

Medical staff in an 18-bed pediatric ICU in a children’s

teaching hospital in Melbourne, 1994; 5-step behavioral

modification program25

Level 3, Level

2

Handwashing rates after

patient contact: 64.8% vs.

10.6%

Medical staff in a 3000-bed tertiary care center in

France, 1994-95; 13-step handwashing protocol 13

Level 3, Level

2

18.6% vs. 4.2% (p<0.0001)
124

Table 12.1. Fourteen studies of practices to improve handwashing compliance (cont.)

Medical staff in two ICUs at a teaching hospital in

Virginia, 1997; 6 education/feedback sessions followed

by introduction of alcohol antiseptic agent22

Level 3, Level

2

Baseline 22%;

Education/feedback 25%;

Alcohol antiseptic 48%;

(p<0.05)

Medical staff in a 14-bed ICU in a tertiary care 

hospital in France, 1998; introduction of alcohol-based

solution21

Level 3, Level

2

60.9% vs. 42.4% (p=0.0001)

All staff in a medical ICU and step-down unit in a large

teaching hospital in Virginia; installation of alcoholbased solution23

Level 3, Level

2

52% vs. 60% (p=0.26)

Medical staff on 2 general inpatient floor at each of 4

community hospitals in New Jersey; patient education

intervention20

Level 3, Level

3

Soap usage (as an indicator of

handwashing) increased by

34% (p=0.021)

* ICU indicates intensive care unit.

† Results are reported as intervention group vs. control group.
125

References

1. Haley RW, Culver DH, White JW, Morgan WM, Emori TG, Munn VP. The efficacy of

infection surveillance and control programs in preventing nosocomial infection in US

hospitals. Am J Epidemiol. 1985;121:182-205.

2. Jarvis WR. Handwashing-the Semmelweis lesson forgotten? Lancet. 1994;344:1311-2.

3. Larson E. A causal link between handwashing and risk of infection? Examination of the

evidence. Infect Control Hosp Epidemiol. 1988;9:28-36.

4. Pittet D. Improving compliance with hand hygiene in hospitals. Infect Control Hosp

Epidemiol. 2000;21:381-386.

5. Newsom SW. Pioneers in infection control. Ignaz Philipp Semmelweis. J Hosp Infect.

1993;23:175-187.

6. Larson E. Skin hygiene and infection prevention: more of the same or different

approaches? Clin Infect Dis. 1999;29:1287-1294.

7. Doebbeling BN, Stanley GL, Sheetz CT, Pfaller MA, Houston AK, Annis L, et al.

Comparative efficacy of alternative handwashing agents in reducing nosocomial infections

in intensive care units. N Engl J Med. 1992;327:88-93.

8. Pittet D, Mourouga P, Perneger TV. Compliance with handwashing in a teaching hospital.

Ann Intern Med. 1999;130:126-130.

9. Graham M. Frequency and duration of handwashing in an intensive care unit. Am J Infect

Control. 1990;18:77-80.

10. Harris AD, Samore MH, Nafziger R, Dirosario K, Roghmann MC, Carmeli Y. A survey on

handwashing practices and opinions of healthcare workers. J Hosp Infect. 2000;45:318-

321.

11. Larson E, Kretzer EK. Compliance with handwashing and barrier precautions. J Hosp

Infect. 1995;30(Suppl):88-106.

12. Ehrenkranz NJ, Alfonso BC. Failure of bland soap handwash to prevent hand transfer of

patient bacteria to urethral catheters. Infect Control Hosp Epidemiol. 1991;12:654-662.

13. Coignard B, Grandbastien B, Berrouane Y, Krembel C, Queverue M, Salomez JL, et al.

Handwashing quality: impact of a special program. Infect Control Hosp Epidemiol.

1998;19:510-513.

14. Larson E, McGeer A, Quraishi A, Krenzischek D, Parsons BJ, Holdford J, et al. Effect of

an automated sink on handwashing practices and attitudes in high-risk units. Infect Control

Hosp Epidemiol. 1991;12:422-428.

15. Jarvis WR. Selected aspects of the socioeconomic impact of nosocomial infections:

morbidity, mortality, cost, and prevention. Infect Control Hosp Epidemiol. 1996;17:552-

557.

16. Larson EL, Bryan JL, Adler LM, Blane C. A multifaceted approach to changing

handwashing behavior. Am J Infect Control. 1997;25:3-10.

17. Kaplan LM, McGuckin M. Increasing handwashing compliance with more accessible

sinks. Infect Control Hosp Epidemiol. 1986;7:408-410.

18. Pittet D, Hugonnet S, Harbarth S, Mourouga P, Sauvan V, Touveneau S, et al.

Effectiveness of a hospital-wide programme to improve compliance with hand hygiene.

Lancet. 2000;356:1307-1312.

19. Donowitz LG. Handwashing technique in a pediatric intensive care unit. Am J Dis Child.

1987;141:683-685.
126

20. McGuckin M, Waterman R, Porten L, Bello S, Caruso M, Juzaitis B, et al. Patient

education model for increasing handwashing compliance. Am J Infect Control.

1999;27:309-314.

21. Maury E, Alzieu M, Baudel JL, Haram N, Barbut F, Guidet B, et al. Availability of an

alcohol solution can improve hand disinfection compliance in an intensive care unit. Am J

Respir Crit Care Med. 2000;162:324-327.

22. Bischoff WE, Reynolds TM, Sessler CN, Edmond MB, Wenzel RP. Handwashing

compliance by health care workers: the impact of introducing an accessible, alcohol-based

hand antiseptic. Arch Intern Med. 2000;160:1017-1021.

23. Muto CA, Sistrom MG, Farr BM. Hand hygiene rates unaffected by installation of

dispensers of a rapidly acting hand antiseptic. Am J Infect Control. 2000;28:273-276.

24. Simmons B, Bryant J, Km N, Spencer L, Arheart K. The role of handwashing in prevention

of endemic intensive care unit infections. Infect Control Hosp Epidemiol. 1990;11:589-

594.

25. Tibballs J. Teaching hospital medical staff to handwash. Med J Aust. 1996; 164: 395-398.

26. Kretzer EK, Larson EL. Behavioral interventions to improve infection control practices.

Am J Infect Control. 1998;26:245-253.

27. Larson E. Handwashing and skin: physiologic and bacteriologic aspects. Infect Control.

1985;6:14-23.

28. Larson EL. APIC Guidelines for handwashing and hand antisepsis in health care settings.

Am J Infect Control. 1995;23:251-269.

29. Voss A, Widmer AF. No time for handwashing!? Handwashing versus alcoholic rub: can

we afford 100% compliance? Infect Control Hosp Epidemiol. 1997;18:205-208.

30. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients.

Excess length of stay, extra costs, and attributable mortality. JAMA. 1994;271:1598-1601.

31. Dubbert PM, Dolce J, Richter W, Miller M, Chapman SW. Increasing ICU staff

handwashing: effects of education and group feedback. Infect Control Hosp Epidemiol.

1990;11:191-193.
127

Chapter 13. Impact of Barrier Precautions in Reducing the Transmission of

Serious Nosocomial Infections

Ebbing Lautenbach, MD, MPH, MSCE

University of Pennsylvania School of Medicine

Background

Many nosocomial infections are easily transferable from patient-to-patient, either via the

hands of health care workers,1,2 or through the contamination of inanimate objects, including

clothing and equipment.3,4 For some infections, the threat to other patients is considered serious

enough that many institutions employ special barrier precautions, such as the use of gloves,

gowns and disposable equipment for all patient contact, in caring for patients colonized or

infected with these pathogens. Vancomycin-resistant enterococci (VRE)5

 and Clostridium

difficile6

 represent 2 typical examples of nosocomial pathogens that may trigger such

precautions.

Although adherence to barrier precautions to prevent the spread of particularly

concerning nosocomial pathogens has obvious face validity, the utility of specific interventions

and the optimal forms they should take remain unclear. This uncertainty may in part reflect the

impact of particular aspects of the epidemiology of the targeted nosocomial pathogens – ie, the

benefit of a given strategy may vary in different settings and with different organisms.

Consequently, this chapter contrasts with the review of handwashing (Chapter 13), a practice for

which the benefit was regarded as sufficiently established to warrant focusing on strategies for

improving compliance. While compliance with barrier precautions is also an important topic and

likely plays a significant role in the efficacy of such interventions, this chapter analyzes the

literature evaluating the benefit of the barrier precautions themselves.

Practice Description

Barrier precautions include any activity designed to prevent the spread of nosocomial

pathogens from patient to patient. This chapter reviews the following 3 practices:

• Use of gowns and gloves for all contact with patients colonized or infected

with VRE and/or C. difficile: Health care workers typically don gloves and

gowns when entering the room of an infected or colonized patient, and

remove them upon exiting (followed immediately by handwashing) to reduce

the likelihood of clothing or equipment contamination that could transmit

pathogens to other patients;

• Use of dedicated or disposable examining equipment for patients colonized or

infected with VRE and/or C. difficile: Hospital equipment (ie, blood pressure

cuffs, thermometers) remains in a patient’s room and is not carried from room

to room; and

• Patient and/or staff cohorting for patients colonized or infected with VRE

and/or C. difficile: Patients colonized or infected with similar pathogens are

admitted to specific floors of the hospital where designated health care

workers care only for patients colonized or infected with these pathogens.
128

Prevalence and Severity of the Target Safety Problem

Nosocomial infections, including C. difficile-associated diarrhea and VRE, significantly

increase the morbidity and mortality of hospitalized patients.5,6 Both infections are also

associated with increased hospital costs. Recent evidence also suggests there may be a

relationship between C. difficile and VRE, with C. difficile infection identified as a risk factor for

VRE infection.7

 The increased incidence of both VRE and C. difficile can be attributed to spread

from patient to patient.5,6 Failure to recognize these dissemination patterns may result in an

inability to contain outbreaks when they occur in the hospital.

C. difficile has been identified as the major, if not only, important cause of infectious

diarrhea that develops in patients after hospitalization, occurring in up to 30% of adult

hospitalized patients who developed diarrhea.5

 One study found an acquisition rate of 13% for

patients hospitalized 1-2 weeks, which increased to 50% for patients hospitalized >4 weeks.8

 In

addition, the incidence of C. difficile infection has increased in recent years, with one study

reporting a 5-fold increase in clinical infection between 1993 and 1996.9 C. difficile infection

increases lengths of stay, often to as long as 18-30 days10,11 and, when fulminant, can lead to

exploratory and therapeutic surgical procedures.12 Mortality attributable to C. difficile, while

reported, occurs in fewer than 5% of patients.13 The costs associated with C. difficile diarrhea,

while not well described, may be as high as $10,000 per patient.14

VRE, first described in 1988, currently accounts for greater than 25% of all nosocomial

enterococci.6

 Early national data suggested that infections with VRE were associated with

mortality rates of over 36%, more than double that of patients with vancomycin-susceptible

(VSE) infections.15 While later studies called some of these results into question,16,17 the most

recent studies have again suggested that vancomycin-resistance carries an independent effect on

mortality.18 VRE infections are also associated with significantly higher hospital costs than those

due to VSE.18

Although C. difficile and VRE are among the most common nosocomial pathogens that

have significant effects on morbidity, mortality, and cost, there are a number of other nosocomial

pathogens which could also be studied. These include pathogens such as methicillin-resistant

Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL) producing

Enterobacteriaceae, Acinetobacter species, and Pseudomonas aeruginosa. While these are all

important nosocomial pathogens, C. difficile and VRE were chosen as examples because they are

extremely common, and they represent both antibiotic-susceptible (C. difficile) and antibioticresistant (VRE) pathogens. Additionally, (unlike MRSA and P. aeruginosa) the epidemiology of

both pathogens is complex, representing both person-to-person spread and association with prior

antibiotic use, allowing for a more comprehensive discussion of the relative merits of both

antimicrobial use interventions and barrier precaution interventions (see Chapter 15 for more

discussion regarding other antimicrobial intervention practices) and their general application to

other pathogens.

Opportunities for Impact

As noted above, both VRE and C. difficile affect a large proportion of hospitalized

patients. Improvements in barrier precaution interventions against these pathogens would have a

tremendous impact. There are few data regarding the percentage of hospitals that employ any

one of a number of barrier precautions (eg, gowns, gloves, disposable thermometers).19 In

addition, while standard practice is to apply barrier precautions for patients with nosocomial

pathogens with demonstrated horizontal spread, compliance with precautions is frequently
129

poor,20 often below 50%.21 Purported reasons for this lack of compliance include lack of

resources and busy staff workload.20 Regardless, these results suggest that the opportunity for

improvement in these practices is great.

Study Designs

A structured search of the PubMed database (including MEDLINE) and review of the

bibliographies of relevant articles identified 19 studies that have examined the implementation of

barrier precaution practices designed to impact the incidence of VRE and/or C. difficile infection

(Table 13.1, 13.2, 13.3). All studies found on literature search were included in this review

except for those reporting very small outbreaks (defined as fewer than 10 cases of C. difficile or

VRE). Sixteen of the reviewed studies were before-after observational cohort studies (Level 3),

in which baseline data regarding incidence of VRE or C. difficile were obtained during an

observational period and compared to a second period after implementation of an intervention.

Crude comparability data on the before and after groups (eg, total admissions, patient census)

were provided in 2 reports22,23 while only one study statistically compared the before and after

groups to assess comparability.24 Three reports25-27 detailed unblinded comparative studies

(Level 2) in which patients on different wards were assigned different interventions. Each of

these studies assessed the comparability of the study groups on the basis of underlying

demographic variables.

Study Outcomes

All of the studies reviewed reported changes in the incidence or prevalence of either VRE

or C. difficile as a result of barrier precaution interventions (Level 1). For studies investigating C.

difficile, all outcomes were reported in terms of clinical infections. For studies investigating

VRE, outcomes were reported as VRE colonization and/or infection rates.

Evidence for Effectiveness of the Practice

As both VRE and C. difficile have clearly been shown to be transferable from patient-topatient, interventions designed to improve barrier precautions yield significant reductions in the

incidence of infection with these two pathogens. All studies that examined the effect of enhanced

barrier precautions on C. difficile infection demonstrated benefit, suggesting that barrier

precaution interventions are effective in controlling its emergence. Most studies employed a

multifaceted approach including several different barrier precaution components. For example,

one study combined use of vinyl gloves and ongoing educational interventions,26 another

included cohorting, culture screening, and daily room disinfection,28 while another combined

reinforcement of enteric precautions, replacement of electronic thermometers, and institution of

closed paper towel dispensers.29 Given the varied components of barrier precaution interventions

instituted in different studies, it is difficult to determine the specific effect of any individual

component.

The evidence of effectiveness of barrier precautions for VRE is somewhat less clear-cut.

All but 427,30-32 of the studies examining the effect of barrier precautions on VRE demonstrated a

benefit, but study design differences and particular epidemiologic trends may account for the

inconsistent findings.

One of the 4 studies that noted no significant effect compared glove use to glove and

gown use.27 The second 30 noted that the emergence of VRE at the study institution was due to

multiple genetically-unrelated strains, suggesting that person-to-person spread was less

important at that site. It is thus not surprising that barrier precautions would have less of an
130

effect. In the third study,32 routine rectal swab surveillance and contact precautions were

instituted in response to a clinical outbreak of VRE and surveillance was continued for only 6

months. Since surveillance was not conducted prior to institution of precautions, it is impossible

to say what the colonization prevalence had been prior to the intervention. Furthermore, as the

authors point out, it may be that the outbreak would have been much worse had the precautions

not been put in place. Finally, no determination of genetic relatedness (and hence spread) was

made in this study. In the fourth study,31 while there was a reduction in the isolation of VRE,

there was not complete eradication. According to the authors, the most likely reason for this lessthan-optimal response was poor compliance with contact precaution guidelines.

Thus, it appears that enhanced barrier precautions are generally effective in reducing the

incidence of VRE but that various aspects of both the epidemiology of the VRE outbreak and the

implementation of guidelines may temper the effectiveness of interventions. Similar to the

studies investigating response of C. difficile to barrier precautions, most studies of VRE

employed several components of barrier precautions as part of a multifaceted approach (Table

13.1). It is thus difficult to determine the specific effect of any individual component.

Potential for Harm

None of the reviewed studies reported any assessment of possible harm as a result of the

barrier precaution interventions. In fact, the implementation of barrier precautions is unlikely to

result in harm to the patient. One potential concern is that time necessary to comply with the

interventions (eg, gowning, gloving), might make health care workers less likely to complete

tasks necessary to provide acceptable patient care. Indeed, it has recently been noted that health

care workers were half as likely to enter the rooms of patients on contact isolation.33

Furthermore, while contact precautions appeared to have little effect on patient examination by

resident physicians, attending physicians were 50% less likely to examine a patient on contact

precautions compared to a patient not on precautions.34 Future studies should address these

concerns by documenting the time required to adhere to barrier precautions, and determining the

potential impact of precautions on patient care.

Another potentially harmful consequence of barrier precaution interventions is the

psychological effect that contact precautions may have on the isolated patient. While research

has examined the effects of sensory deprivation and social isolation, a recent review of the

literature noted little progress in the investigation of the psychological effects of contact

isolation.35

Costs and Implementation

It seems apparent that the more complicated an intervention, the less likely health care

workers will adhere to it. While 2 studies noted compliance with barrier precautions at close to

90%,21,24 others noted levels closer to 70%.31 One study actually noted compliance levels to be

significantly higher in those health care workers who used both gowns and gloves compared to

those using only gowns.27 This somewhat counterintuitive finding suggests that other factors

may be at play in influencing compliance. Of the reviewed studies that reported compliance

levels, all did so relatively shortly after the initial implementation of interventions. Future studies

should assess compliance with guidelines over a longer period.

Four studies reported the costs of specific interventions. Implementation of use of

disposable thermometers was estimated at $14,055 per year at a 343-bed institution.22 Another

study of the impact of disposable thermometers estimated that the cost per prevented C. difficile

infection would be approximately $611.25 A study using a multifaceted approach estimated that
131

the annual expenses due directly to increased demand for gowns and gloves were approximately

$11,000.31 Finally, a multifaceted intervention at a 254-bed long-term care facility which

included education, gowns and gloves for resident contact, no sharing of personal equipment,

and daily double cleaning of resident rooms and wheelchairs, estimated the total cost of the

intervention to be $12,061 Canadian (approximately $8000 US).36

The costs of implementing a program to enhance barrier precaution practices must be

balanced against the potential cost savings due to decreased incidence of nosocomial infections.

Both VRE and C. difficile infections have been associated with significantly increased length of

hospital stay.5,6 Preventing even a small number of these infections is likely to have a significant

financial impact. While several of the reviewed studies documented costs associated with

various interventions,22,25,26,31,36 no study systematically compared these costs to the potential

cost savings of infections prevented.

Comment

The majority of reviewed studies demonstrated a significant reduction in the incidence of

VRE or C. difficile following barrier precaution interventions. The fact that not all studies found

a benefit suggests that future studies should identify those scenarios (eg, outbreak, endemic

colonization, etc.) in which attention to barrier precautions is most likely to be beneficial. In

addition, it is possible that a combined intervention involving both enhanced barrier precautions

as well as antibiotic formulary interventions might be needed in order to effect the greatest

possible change in VRE and C. difficile infection rates. While these studies, much like those that

examined the impact of antibiotic use practices, demonstrated short-term success, future studies

should determine the efficacy of such interventions over the long term. Finally, the costeffectiveness of such strategies should be investigated.
132

Table 13.1. Studies of multifaceted approaches with and without “cohorting”*

Study Setting Compliance Study

Design,

Outcomes

Change in C. difficile or VRE

725-bed academic medical center in

Philadelphia in 1987-88: beforeafter study of impact of

multifaceted intervention (isolation

precautions, clindamycin

restriction) on C. difficile37

NA Level 3,

Level 1

Cases of C. difficile decreased

from 1.47 cases/100 hospital

discharges in 1987 to 0.74

cases/100 hospital discharges by

the second half of 1988

350-bed acute care hospital in

Virginia in 1987-96: before-after

study of impact of multifaceted

intervention on C. difficile

infections23

NA Level 3,

Level 1

Mean annual new cases of C.

difficile decreased from

155/year in the before period to

67/year in the after period

(p<0.05).

840-bed tertiary care center in

Brussels in 1989-90: impact of a

multifaceted infection control

intervention, including cohorting,

on incidence of C. difficile28

NA Level 3,

Level 1

Incidence of C. difficile

decreased from 1.5 cases/1000

admissions to 0.3 cases/1000

admission (protective efficacy

73%, 95% CI: 46-87%)

Bone marrow transplant unit of a

large academic medical center in

Texas in 1995: impact of

multifaceted infection control

intervention on C. difficile attack

rate29

NA Level 3,

Level 1

Attack rate for third week in

May was 60%. Following

intervention, rate dropped to

17% for remainder of May, 21%

for June, and 7% for July

(p<0.05)

Tertiary-care Veterans Affairs

Medical Center in Brooklyn in

1991-95: impact of multifaceted

infection control intervention on

VRE rates30

NA Level 3,

Level 1

Incidence of VRE cases per

1000 admissions was 0.6 in

1991, 3.3 in 1992. Following

intervention, the rates were 8.0

in 1993 and 9.2 in 1994

22-bed oncology unit in a 650-bed

tertiary care hospital in New York

in 1993-95: impact of multifaceted

infection control program, including

cohorting, on VRE infection and

colonization24

91.7% of

persons who

entered room

used gowns

and gloves

appropriately

Level 3,

Level 1

Incidence of VRE bloodstream

infection (patients per 1000

patient-days) decreased from

2.1 to 0.45 (p=0.04). VRE

colonization decreased from

20.7 to 10.3 (p<0.001).

375-bed community hospital in

Indianapolis in 1995-96: impact of

cohorting on VRE prevalence21

Compliance

with recommendations

rose from

22% to 88%

(p<0.001)

Level 3,

Level 1

VRE prevalence decreased from

8.1% to 4.7% (p=0.14). VRE

among patients whose VRE

status was unknown before

cultures were obtained

decreased from 5.9% to 0.8%

(p=0.002).
133

254-bed long-term care facility in

Toronto in 1996-97: impact of

barrier precautions including

cohorting on prevalence of VRE36

NA Level 3,

Level 1

4/85 (4.7%) patients initially

screened were VRE colonized.

No patients in subsequent

screenings were positive.
134

Table 13.1. Studies of multifaceted approaches with and without “cohorting” (cont.)

23-bed oncology unit in a 1300-

bed teaching hospital in South

Africa in 1998: impact of barrier

precautions including cohorting

on VRE prevalence39

NA Level 3,

Level 1

VRE colonization decreased from

19/34 (55%) patients to 1/14 (7%)

following implementation of

infection control interventions

347-bed tertiary care medical

center in Massachusetts in 1993:

impact of a multifaceted infection

control intervention including

cohorting on VRE infection and

colonization31

Overall

handwashing

complianc

e was 71%

Level 3,

Level 1

In the year prior interventions,

116 patients were colonized or

infected with VRE, compared

with 126 in the year after

implementation.

* NA indicates not applicable; VRE, vancomycin-resistant enterococci.
135

Table 13.2. Studies of barrier precaution interventions*

Study Setting Compliance Study

Design,

Outcomes

Change in C. difficile or VRE

370-bed academic medical center in

Massachusetts in 1991-92: beforeafter study of impact of infection

control interventions on C. difficile

incidence38

NA Level 3,

Level 1

Incidence of C. difficile increased

from 0.49% to 2.25% from 1989

to 1993. Following interventions,

incidence of C. difficile decreased

to 1.32%

Veterans Administration Medical

Center in Minnesota in 1986-87:

impact of universal glove use on

incidence of C. difficile26

Mean glove

use/100 pts:

4539 on glove

ward; 3603 on

control ward

(p=NS)

Level 2,

Level 1

Incidence of C. difficile on glove

wards decreased from 7.7/1000

patients discharges to 1.5/1000

(p=0.015). No significant change

in incidence on the control wards

8-bed combined medical and surgical

ICU in a 235-bed acute care hospital

in New York City in 1990-91: impact

of barrier precautions on VRE

colonization1

NA Level 3,

Level 1

16 patients infected or colonized

with VRE identified over 6 months

period. No new VRE infection or

colonization in the 2 months after

intervention.

250-bed university-affiliated hospital

in Rhode Island in 1991-92: impact

of sequential barrier precaution

intervention on VRE40

NA Level 3,

Level 1

13 patients with VRE identified

over 8 month period. In the 3

months after the first intervention

(private room + gloves) 20

patients were found to have VRE.

In the 6 months after the second

intervention (gowns added), 4

patients were VRE positive.

181 consecutive patients admitted to

the medical ICU in a 900-bed urban

teaching hospital in Chicago in 1994-

95: comparison of impact of gown

and glove vs. glove on incidence of

VRE colonization27

Compliance in

glove and

gown group,

79%; glove

group, 62%

(p<0.001)

Level 2,

Level 1

24 (25.8%) of the glove and gown

group acquired VRE in the ICU

compared to 21 (23.9%) of those

patients in the gown only room

(p=NS)

550-bed tertiary teaching hospital in

Minneapolis in 1993-94: impact of

barrier precautions on VRE

colonization32

NA Level 3,

Level 1

Weekly rectal swab surveillance

performed. Rates of VRE

colonization remained at 7-9%

throughout 6 month study period

* ICU indicates intensive care unit; NA, not applicable; NS, not statistically significant; and

VRE, vancomycin-resistant enterococci.
136

Table 13.3. Studies of use of dedicated or disposable examining equipment*

Study Setting Complianc

e

Study

Design,

Outcomes

Change in C. difficile or VRE

343-bed acute hospital and

538-bed skilled nursing

facility in New York: beforeafter study of impact of

replacing electronic

thermometers with disposable

thermometers on C. difficile

infection rate22

100%

replacemen

t of

electronic

thermometers

Level 3,

Level 1

Incidence of C. difficile decreased

from 2.71 to 1.76 cases per 1000

patients in the acute hospital

(p<0.01)

Incidence of C. difficile decreased

from 0.41 to 0.11 cases per 1000

patient days in the skilled nursing

facility (p<0.01)

20 inpatient units in a 700-bed

university hospital in

Virginia: randomized

crossover trial of impact of

disposable thermometers for

prevention of C. difficile25

100%

compliance

with use of

specific

types of

thermometers

Level 2,

Level 1

Incidence of C. difficile was 0.16

cases/1000 patient days in the

intervention group compared to

0.37/1000 patient days in controls

(RR 0.44, 95% CI: 0.21-0.93;

p=0.026]

343-bed acute care facility in

New York in 1992: impact of

change to tympanic

thermometers on VRE

incidence22

100%

switch to

tympanic

thermometers

Level 3,

Level 1

Tympanic thermometer use

resulted in risk reduction for VRE

of 60% (RR 0.41, 95% CI: 0.31-

0.55)

* CI indicates confidence interval; RR, relative risk; and VRE, vancomycin-resistant enterococci.
137

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27. Slaughter S, Hayden MK, Nathan C, Hu TC, Rice T, Van Voorhis J, et al. A comparison of

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with a hospital-wide outbreak of vancomycin-resistant enterococci. Am J Infect Control.

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31. Lai KK, Kelley AL, Melvin ZS, Belliveau PP, Fontecchio SA. Failure to eradicate

vancomycin-resistant enterococci in a university hospital and the cost of barrier

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32. Wells CL, Juni BA, Cameron SB, Mason KR, Dunn DL, Ferrieri P, et al. Stool carriage,

clinical isolation, and mortality during an outbreak of vancomycin-resistant enterococci in

hospitalized medical and/or surgical patients. Clin Infect Dis. 1995;21:45-50.

33. Kirkland KB, Weinstein JM. Adverse effects of contact isolation. Lancet. 1999;354:1177-

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36. Armstrong-Evans M, Litt M, McArthur MA, Willey B, Cann D, Liska S, et al. Control of

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Infect Control Hosp Epidemiol. 1999;20:312-317.

37. Brown E, Talbot GH, Axelrod P, Provencher M, Hoegg C. Risk factors for Clostridium

difficile toxin-associated diarrhea. Infect Control Hosp Epidemiol. 1990;11:283-290.

38. Lai KK, Melvin ZS, Menard MJ, Kotilainen HR, Baker S. Clostridium difficile-associated

diarrhea: epidemiology, risk factors, and infection control. Infect Control Hosp Epidemiol.

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in South Africa: effective use of limited resources. J Hosp Infect. 2000;44:294-300.

40. Boyce JM, Opal SM, Chow JW, Zervos MJ, Potter-Bynoe G, Sherman CB, et al. Outbreak

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140
141

Chapter 14. Impact of Changes in Antibiotic Use Practices on Nosocomial

Infections and Antimicrobial Resistance – Clostridium Difficile and

Vancomycin-resistant Enterococcus (VRE)

Ebbing Lautenbach, MD, MPH, MSCE

University of Pennsylvania School of Medicine

Background

As discussed in the chapters on handwashing and barrier precautions (Chapters 12 and

13), hospital infection control has historically focused on preventing the transmission of

nosocomial pathogens—either from patient to patient or from provider to patient. The potential

role of overseeing hospital-wide antibiotic use as an infection control measure has also been

recognized for many years.1

 With the widespread emergence of nosocomial antibiotic-resistant

infections over the past 10-15 years, institutional efforts to control antibiotic use have become a

priority for infection control.2,3

The practices reviewed in this chapter involve institutional efforts to control antibiotic

use as a means of controlling complications of antibiotic overuse or misuse. In evaluating the

potential benefits of these practices, the focus is on the impacts of antibiotic use on infections

with vancomycin-resistant enterococci (VRE)4

 and Clostridium difficile.5 These pathogens

represent two of the most important nosocomial pathogens with relationships to inappropriate

antibiotic use. Moreover, as suggested by recent evidence, infection with C. difficile may

represent a risk factor for infection with VRE.6

Practice description

Interventions designed to limit the use of antibiotics may take many forms. Specific

practices reviewed in the chapter include:

• Infectious diseases physician approval7 – all requests for an antibiotic are

discussed with an infectious diseases physician who decides whether use is

appropriate

• Monitoring of antibiotic use by pharmacy service8 – pharmacists monitor the

use of certain antibiotics and make recommendations for changes to the

prescriber

• Guidelines for antimicrobial use8 – dissemination to physicians of guidelines

describing appropriate and inappropriate use

• Therapeutic substitution9 – use of one agent replaced by another agent with

similar spectrum of activity

• Computer-assisted prescribing10 – computer-based restriction of agent with

extra prompts requesting documentation of indication for agent

• Antibiotic-management program (AMP)11 – continuation of antibiotic after a

specific duration requires approval from either an infectious diseases

physician or pharmacist on the AMP
142

Prevalence and Severity of the Target Safety Problem

This chapter focuses on 2 of the most important nosocomial pathogens: VRE and C.

difficile. VRE currently accounts for greater than 25% of all nosocomial enterococci4

 and confers

an increased risk of death, independent of comorbid conditions that may have initially led to the

infection.12 VRE infections are also associated with significantly higher hospital costs than those

due to vancomycin-sensitive enterococci (VSE)12 (see Chapter 13). C. difficile represents the

major, if not only, important infectious cause of nosocomial diarrhea.5

 Although death

attributable to C. difficile occurs in less than 5% of patients,17 the impact of C. difficile infection

remains significant. Patients may require substantially longer lengths of hospital stay—upwards

of 18-30 days,18,19 with exploratory and therapeutic surgical procedures required in severe

cases.20 It has also been suggested that more debilitated patients (eg, in rehabilitation centers or

long-term care facilities) may be at even greater risk for increased morbidity and mortality due to

C. difficile infection.21 The costs associated with C. difficile diarrhea, while not well described,

are estimated to be as high as $10,000 per patient22 (see Chapter 13).

Opportunities for Impact

Over half of all hospitalized patients are treated with antibiotics.23 The antibiotics

represent a significant portion of overall health care costs, accounting for between 20% and 50%

of total hospital drug expenditures.23 It has been estimated that 50% of all antibiotics prescribed

are either at the wrong dose, the wrong drug, or taken for the wrong duration.24,25 These findings

suggest that there is significant room for improvement in antibiotic prescribing practices.

Most hospitals employ formulary restrictions for certain medications (particularly

expensive agents, selecting one drug from a group of equivalent agents). However, only a

minority of hospitals uses formulary restrictions to limit the use of entire antibiotic classes or

specific agents. Those hospitals that do employ antimicrobial formulary restrictions most often

do so as a means of controlling costs, rather than as an infection control measure.26 Thus, there

remain substantial opportunities to expand upon these existing formulary programs to control the

emergence of antimicrobial resistance.

Study Designs

A structured search of the PubMed database (including MEDLINE) and review of the

bibliographies of relevant articles identified 10 studies that have examined methods to change

antibiotic use with respect to VRE and/or C. difficile infection (Table 14.1). All of these studies

were before-after observational cohort studies (Level 3) in which baseline data regarding

incidence of VRE or C. difficile were obtained during an observational period and compared

with a second time period after an intervention had been implemented. Data on baseline

comparability of the before and after groups were not reported in 6 studies.8-11,21,27 Two studies

only reported similar admission and census rates during the before and after time periods,7,28

while 2 studies compared patients in the 2 time periods on the basis of numerous variables.29,30

Study Outcomes

All of the studies reviewed reported changes in the clinical incidence or prevalence of

either VRE or C. difficile as a result of antibiotic practice interventions (Level 1). Studies

investigating C. difficile measured clinical infections. Studies investigating VRE examined VRE

infection11 or VRE colonization.8-10,27
143

Evidence for Effectiveness of the Practice

Of the 10 studies listed in Table 14.1, all but 38,11,21 showed significant reductions in the

incidence of C. difficile or VRE following practice changes. Several possibilities may explain the

negative findings of these 3 studies. First, the interventions analyzed might not have produced

significant alterations in antibiotic use, so that infection rates with the target pathogens remained

unchanged. Second, it is possible that patient-to-patient spread of these pathogens limited the

efficacy of the interventions, as this mode of transmission is well known to occur for both VRE

and C. difficile, usually via the hands of health care workers (see also Chapter 13).31,32 Third,

since environmental contamination occurs with both these pathogens, successful control of these

organisms may require enhanced disinfection procedures in some cases.33,34 Targeting antibiotic

use may not be sufficient to reduce incidence of these pathogens since a significant number of

infected or colonized patients may serve as reservoirs. Under this scenario, the argument for

barrier precautions as an adjunct measure to prevent spread of organisms from patient to patient

becomes more persuasive (see Chapter 13). Indeed, although changes in antibiotic use practice

were the primary intervention in all of the studies reviewed here, one study included a

component of enhanced barrier precautions in the intervention.21 Future studies should

investigate the impact of such multifaceted interventions, both for VRE and C. difficile as well as

for other nosocomial pathogens.

Other Potential Benefits

Although not the focus of this chapter, the practices reviewed here may have a beneficial

impact on other emerging nosocomial pathogens strongly associated with inappropriate

antibiotic use, such as extended-spectrum beta-lactamase (ESBL) producing

Enterobacteriaceae.35 In addition, although we have focused on control of VRE as an end in

itself, a primary motivation to achieve this goal is the need to delay the emergence of

vancomycin-resistance in Staphylococcus aureus.

36,37 As S. aureus represents the most common

nosocomial infection,38 the development of high-level vancomycin resistance among

staphylococci would constitute a public health disaster.39

Thus, practices that decrease the prevalence of VRE may play an important, albeit

indirect, role in preventing or delaying this occurrence.

Potential for Harm

Few of the reviewed studies reported any assessment of possible harm as a result of the

antibiotic use practice interventions. One potential result of interventions designed to reduce the

use of one antibiotic, or antibiotic class, is the subsequent increase in the use of another class of

agents to compensate. In fact, one reviewed study7

 noted an increase in the use of other antianaerobic agents as clindamycin use decreased. Whether changes in antibiotic use results in

changes in antimicrobial susceptibilities, either in the pathogen under study (eg, VRE, C.

difficile) or in other nosocomial pathogens, it is a fertile ground for future study.

Finally, efforts to decrease use of certain antibiotics might increase infection rates due to

inappropriate withholding of appropriate antibiotics. However, one reviewed study 10 noted no

increase in rates of surgical site infections following decrease in the use of vancomycin for

preoperative prophylaxis (see also Subchapter 20.1).
144

Costs and Implementation

The costs of implementing a program to alter antibiotic use practices must be balanced

against potential cost savings. Sources of savings may be reduced antibiotic use, use of less

expensive agents rather than the more expensive newer agents, and potentially, reduced costs

due to decreased incidence of nosocomial infections as a result of interventions. Although

several studies reported cost savings due only to decreased antibiotic use,10,11,29 analyses taking

into account costs related to subsequent infections (or infections prevented) have been sparse.

One study noted that cost savings from decreased use of clindamycin offset the expenditures due

to increased use of other antibiotics.7

 The authors suggested that if each case of C. difficile

resulted in a cost of $2000, the savings to the hospital of the intervention could approach

$162,000 annually based on the number of cases averted.7

Another cost of antibiotic use interventions is the expense of ongoing monitoring of

antibiotic use and antimicrobial susceptibilities of nosocomial pathogens. Effective

recommendation of certain antimicrobial agents over others requires access to (and financial and

logistic support for) routine antimicrobial susceptibility testing. Monitoring institutional

resistance patterns is vital in order to make required formulary changes in response to emerging

resistance patterns and to determine the most effective agents given prevailing susceptibility

patterns.

Comment

Given the strong association between antibiotic use and subsequent infection

(demonstrated for both C. difficile and VRE), it is not surprising that changes in antibiotic use

practices can reduce the incidence of infection with these 2 pathogens. The majority of reviewed

studies demonstrated a significant reduction in the incidence of VRE or C. difficile following

interventions to change antibiotic use practice. While these studies all demonstrated short-term

success, future studies should confirm the efficacy of such interventions over the long term. In

addition, the effectiveness and feasibility of combining antibiotic practice strategies with efforts

to enhance barrier precautions (Chapter 13) should be investigated. Finally, the costeffectiveness of such strategies (taking into account both the costs associated with monitoring

and maintaining sound antibiotic use practices and the costs associated with nosocomial

antibiotic-resistant infections) should be investigated.
145

Table 14.1. Before-after studies of practices to improve antibiotic use*

Study Setting and Intervention Outcomes Results: before vs. after practice

Elderly care unit of a large teaching hospital in

England, 1984-85; Changes in empiric

antibiotic regimens29

Level 1 C. difficile infections decreased from 37

to 16 cases (p=0.002).

Chronic care facility in Baltimore, 1985-86;

multifaceted intervention21

Level 1 Patients with C. difficile toxin decreased

from 28% to 24% (p=NS); Patients with

C. difficile culture increased from 33%

to 42% (p=NS)

Veterans Affairs Medical Center in Arizona,

1990-92; restriction of clindamycin use28

Level 1 C. difficile infections decreased from

7.7 to 1.9 cases/month (p<0.001)

660-bed Veterans Affairs hospital in

California, 1992-94; removal of antibiotic

restrictions30

Level 1 Monthly incidence of C. difficile

infections per 1,000 admissions

increased from 3.4 to 6.2 (p<0.05)

703-bed Veterans Affairs Medical Center in

Virginia, 1993-94; restriction of clindamycin

use7

Level 1 C. difficile infections decreased from

11.5 to 3.33 cases/month (p<0.001)

557-bed academic medical center in Maryland,

1994; restriction of vancomycin use8

Level 2 Mean monthly prevalence of VRE

decreased from 26% to 25% (p=NS)

35-bed hematologic malignancy unit in a large

medical center in England, 1994-95; sequential

antimicrobial formulary changes9

Level 2 VRE colonization for phases 1, 2, and 3

were 57%, 19%, 36%, respectively

(p<0.001 for phase 1 vs. 2; p=0.08 for

phase 2 vs. 3)

Large academic medical center in Virginia,

1994-95; computer-based restriction of

vancomycin use10

Level 2 VRE colonization decreased (p<0.001,

test for trend)

310-bed Veterans Affairs medical center in

New York, 1995; restriction of multiple

antibiotics27

Level 2 Point prevalence of VRE decreased

from 42% to 15% (p<0.001)

725-bed teaching hospital in Philadelphia,

1995-96; restriction of vancomycin use11

Level 2 Incidence of VRE was unchanged at

30% (p=NS)

* NS indicates not statistically significant; VRE, vancomycin-resistant entercocci.
146

References

1. Kunin CM, Tupasi T, Craig WA. Use of antibiotics. A brief exposition of the problem and

some tentative solutions. Ann Intern Med. 1973;79:555-560.

2. Gaynes R. The impact of antimicrobial use on the emergence of antimicrobial-resistant

bacteria in hospitals. Infect Dis Clin North Am. 1997;11:757-765.

3. Goldmann DA, Huskins WC. Control of nosocomial antimicrobial-resistant bacteria: a

strategic priority for hospitals worldwide. Clin Infect Dis. 1997;24:S139-145.

4. Murray BE. Vancomycin-resistant enterococcal infections. N Engl J Med. 2000;342:710-

721.

5. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis.

1998;26:1027-1036.

6. Roghmann MC, McCarter RJ, Brewrink J, Cross AS, Morris JG. Clostridium difficile

infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in

VRE-colonized patients with acute leukemia. Clin Infect Dis. 1997;25:1056-1059.

7. Climo MW, Israel DS, Wong ES, Williams D, Coudron P, Markowitz SM. Hospital-wide

restriction of clindamycin: effect on the incidence of Clostridium difficile-associated

diarrhea and cost. Ann Intern Med. 1998;128:989-995.

8. Morris JG, Shay DK, Hebden JN, McCarter RJ, Perdue BE, Jarvis W, et al. Enterococci

resistant to multiple antimicrobial agents, including vancomycin. Establishment of

endemicity in a university medical center. Ann Intern Med. 1995;123:250-259.

9. Bradley SJ, Wilson ALT, Allen MC, Sher HA, Goldstone AH, Scott GM. The control of

hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing

antibiotic usage. J Antimicrob Chemother. 1999;43:261-266.

10. Anglim AM, Klym B, Byers KE, Scheld WM, Farr BM. Effect of a vancomycin restriction

policy on ordering practices during an outbreak of vancomycin-resistant Enterococcus

faecium. Arch Intern Med. 1997;157:1132-1136.

11. Morgan AS, Brennan PJ, Fishman NO. Impact of a vancomycin restriction policy on use

and cost of vancomycin and incidence of vancomycin-resistant enterococcus. Ann

Pharmacother. 1997;31:970-973.

12. Stosor V, Peterson LR, Postelnick M, Noskin GA. Enterococcus faecium bacteremia: does

vancomycin resistance make a difference? Arch Intern Med. 1998;158:522-527.

13. Clabots CR, Johnson S, Olson MM, Peterson LR, Gerding DN. Acquisition of Clostridium

difficile by hospitalized patients: evidence of colonized new admissions as the source of

infection. J Infect Dis. 1992;166:561-567.

14. Wilcox MH, Smyth ETM. Incidence and impact of Clostridium difficile infection in the

UK, 1993-1996. J Hosp Infect. 1998;39:181-187.

15. Gerding DN, Olson MM, Peterson LR, et al. Clostridium difficile-associated diarrhea and

colitis in adults: a prospective case-controlled epidemiologic study. Arch Intern Med.

1986;146:95-100.

16. Yablon SA, Krotenberg, Fruhmann K. Clostridium difficile-related disease: evaluation and

prevalence among inpatients with diarrhea in two freestanding rehabilitation hospitals.

Arch Phys Med Rehabil. 1993;74:913.

17. Olson MM, Shanholtzer CJ, Lee JT, Gerding DN. Ten years of prospective Clostridium

difficile-associated disease surveillance and treament at the Minneapolis VA Medical

Center, 1982-1991. Infect Control Hosp Epidemiol. 1994;15:371-381.
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18. MacGowan AP, Brown I, Feeney R, Lovering A, McCulloch SY, Reeves DS. Clostridium

difficile associated diarrhea and legnth of hospital stay. J Hosp Infect. 1995;31:241-244.

19. Riley TV, Codde JP, Rouse IL. Increase length of stay due to Clostridium difficile

associated diarrhoea. Lancet. 1995;345:455-456.

20. Kent KC, Rubin MS, Wroblewski L, Hanff PA, Sline W. The impact of Clostridium

difficile on a surgical service. Ann Surg. 1998;227:296-301.

21. Bender BS, Laughon BE, Gaydos C, Forman MS, Bennett R, Greenough WB, et al. Is

Clostridium difficile endemic in chronic-care facilties? Lancet. 1986;2:11-13.

22. Spencer RC. Clinical impact and associated costs of Clostridium difficile-associated

disease. J Antimicrob Chemother. 1998;41(Suppl C):C5-C12.

23. Pestotnik SL, Classen DC, Evans RS. Implementing antibiotic practice guidelines through

computer-assisted decision support: clinical and financial outcomes. Ann Intern Med.

1996;124:884-890.

24. Yates RR. New intervention strategies for reducing antibiotic resistance. Chest.

1999;115:24S-27S.

25. Piquette RK. A targeted review of vancomycin use. Can J Hosp Pharm. 1991;44:83-7.

26. John JF, Fishman NO. Programmatic role of the infectious diseases physician in

controlling antimicrobial costs in the hospital. Clin Infect Dis. 1997;24:471-485.

27. Quale J, Landman D, Saurina G, Atwood E, DiTore V, Patel K. Manipulation of a hospital

antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin

Infect Dis. 1996;23:1020-1025.

28. Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN. Decrease in nosocomial

Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med.

1994;120:272-277.

29. McNulty C, Logan M, Donald IP, Ennis D, Taylor D, Baldwin RN, et al. Successful

control of Clostridium difficile infection in an elderly care unit through use of a restrictive

antibiotic policy. J Antimicrob Chemother. 1997;40:707-711.

30. Ho M, Yang D, Wyle FA, Mulligan ME. Increased incidence of Clostridium difficileassociated diarrhea following decreased restriction of antibiotic use. Clin Infect Dis.

1996;23 (suppl 1):S102-S106.

31. Handwerger S, Raucher B, Altarac D, Monka J, Marchione S, Singh KV, et al. Nosocomial

outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin, and

gentamicin. Clin Infect Dis. 1993;16:750-755.

32. Chang VT, Nelson K. The role of physical proximity in nosocomial diarrhea. Clin Infect

Dis. 2000;31:717-722.

33. Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of

Clostridium difficile. Clin Infect Dis. 2000;31:995-1000.

34. Byers KE, Durbin LJ, Simonton BM, Anglim AM, Adal KA, Farr BM. Disinfection of

hospital rooms contaminated with vancomycin-resistant Enterococcus faecium. Infect

Control Hosp Epidemiol. 1998;19:261-264.

35. Jacoby GA. Extended-spectrum beta-lactamases and other enzymes providing resistance to

oxyimino-beta-lactams. Infect Dis Clin North Am. 1997;11:875-887.

36. Michel M, Gutmann L. Methicillin-resistant Staphylococcus aureus and vancomycinresistant enterococci: therapeutic realities and possibilities. Lancet. 1997;349:1901-1906.

37. Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, et al.

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate

Staphylococcus aureus Working Group. N Engl J Med. 1999;340:493-501.
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38. Archer GL. Staphylococcus aureus: a well-armed pathogen. Clin Infect Dis. 1998;26:1179-

1181.

39. Edmond MB, Wenzel RP, Pasculle AW. Vancomycin-resistant Staphylococcus aureus:

perspectives on measures needed for control. Ann Intern Med. 1996;124:329-334.
149

Chapter 15. Prevention of Nosocomial Urinary Tract Infections

Sanjay Saint, MD, MPH

University of Michigan School of Medicine

Background

Many hospitalized patients require the placement of indwelling urinary catheters for days

or even weeks at a time.1

 Only a minority of patients develop urinary tract infections because of

the presence of these devices,2,3 but the frequency of their use produces substantial overall

morbidity for patients and costs to the health care system. Urinary tract infections (UTIs)

account for up to 40% of nosocomial infections,4,5 with urinary catheter-related infections

causing the vast majority of nosocomial UTIs.6

 Each hospital-acquired UTI adds approximately

$675 to the costs of hospitalization. When bacteremia develops, this additional cost increases to

at least $2800.2

Because of the substantial complications and costs associated with the use of urinary

catheters, a number of practices have been evaluated in an effort to reduce the incidence of

urinary catheter-related infections. This chapter reviews the evidence supporting the use of silver

alloy coated urinary catheters, and, because of its similarity, the recently described practice of

using urinary catheters impregnated with the antibiotic combination of minocycline and

rifampin. Subchapter 15.2 reviews the evidence supporting the use of suprapubic catheters as an

alternative to urethral catheters.

Subchapter 15.1. Use of Silver Alloy Urinary Catheters

Practice Description

Silver is a highly effective antibacterial substance, which can be applied to various types

of catheters. (See Subchapter 16.2 for a discussion of intravascular catheters coated with a

combination of silver sulfadiazine and chlorhexidine). Multiple studies have suggested that

silicone urethral catheters coated with hydrogel and silver salts reduce the risk of developing

bacteriuria, compared with standard latex urethral catheters (Foley catheters). As shown in a

recent meta-analysis, this benefit applies to catheters coated with silver alloy (which are coated

on both internal and external surfaces of the catheter), but not silver oxide (which are coated on

the external catheter surface only). Consequently, this chapter focuses only on studies evaluating

silver alloy catheters, and the use of catheters coated with antimicrobials.8

Prevalence and Severity of the Target Safety Problem

Almost one million episodes of nosocomial UTI occur annually in the United States.9

Each year approximately 96 million urethral catheters are sold worldwide. Of these, nearly 25%

are sold in the United States.3

 The daily rate of bacteriuria in catheterized patients ranges from 3

to 10%, with the incidence directly related to the duration of catheterization.4

 Among patients

with bacteriuria, 10 to 25% will develop symptoms of local urinary tract infection,2,10 such as

suprapubic or flank pain. The development of catheter-related bacteriuria carries with it a 2.8-

fold increased risk of death, independent of other co-morbid conditions and disease severity.11,12

Bacteremia results from catheter-related bacteriuria in approximately 3% of patients, and

invariably represents a serious complication.2,3

Beyond the morbidity and mortality associated with indwelling catheters, catheter-related

infection results in substantially increased health care costs. Data suggest that each episode of
150

hospital-acquired symptomatic catheter-related UTI costs an additional $676, and each episode

of catheter-related nosocomial bacteremia costs a minimum of $2836.2

Estimates from one university hospital, based on data from almost 20 years ago, were

that hospital-acquired UTI led to approximately $204,000 in additional expenses per year.13

More recent data are unavailable, but the institutional costs attributable to catheter-related

infection are clearly substantial.

Opportunities for Impact

Since catheter-related UTI is the leading cause of nosocomial infection in the United

States and is associated with increased morbidity and costs, any intervention that reduces the

incidence of catheter-related UTI is potentially important. Currently, it is unknown what

proportion of patients with indwelling catheters receives silver alloy catheters, however it is

likely to be the minority.

Study Designs

As shown in Table 15.1.1, a meta-analysis7

 which included 4 randomized clinical

trials,14-17 compared the efficacy of silver catheters with standard, non-coated catheters. Five

additional studies18-22 have appeared since publication of this meta-analysis. In 3 of these

studies,18,20,22 the patient represented the unit of analysis. Another study employed a randomized

crossover design (Level 1), randomizing wards rather than individual patients.19 The final study

used a prospective, before-after design at 5 different hospitals (Level 2).21

The patient populations for these studies included patients on various hospital services

including urology, internal medicine, neurology, and the intensive care unit. In general, the

studies included patients expected to be catheterized for at least 2 days. Since the patients resided

in acute care hospitals rather than extended care centers, most were catheterized for 10 days or

less. Several studies specified that patients given concomitant antibiotics were excluded.15-18

Study Outcomes

The individual trials and the meta-analysis focused primarily on the surrogate outcome of

bacteriuria (Level 2). The definition of bacteriuria varied somewhat in the studies. However,

low-level growth from a catheterized specimen (ie, 102

 colony forming units (CFU) /mL) usually

progresses within days to concentrations of greater than 104

 CFU/mL unless antibiotic therapy is

given.23 Unfortunately, none of the studies was adequately powered to detect a significant

difference in the clinically more important outcomes of catheter-related bacteremia or death.

Though bacteriuria is a surrogate endpoint,24 it is probably appropriate to use since it is a

component of the only causal pathway in the disease process between catheterization and an

important clinical outcome (eg, symptomatic UTI or catheter-related bacteremia). One study did

report differences in secondary bloodstream infections.19
151

Evidence for Effectiveness of the Practice

The 4 clinical trials14-17 of silver alloy catheters included in the meta-analysis7

 all showed

a significant reduction in the development of catheter-associated bacteriuria. As shown in Table

15.1.1, studies published after the meta-analysis have reported more mixed results. Several of the

studies have shown a statistically significant benefit of silver alloy catheters, but with a smaller

relative risk reduction compared to that reported in the meta-analysis.19,21,22 However, one study

failed to find a significant benefit associated with silver alloy catheters,20 and another found

benefit from silver alloy catheters in those given such catheters for about 5 days, but not in those

given the catheter for 14 days.18 A formal update of the previous meta-analysis would be helpful,

but is beyond the scope of the current report.

Potential for Harm

There is likely minimal harm from the use of silver alloy urinary catheters. The one

theoretical harm involves the development of antimicrobial resistance. However, since silver is

not used systemically in the form of an antimicrobial agent for treatment, the clinical

significance of antimicrobial resistance to silver is unclear.

Costs and Implementation

Each silver alloy urinary catheter tray costs about $5.30 more than a standard, non-coated

urinary catheter tray. However, a recent economic evaluation indicates that when all the clinical

and economic costs are accounted for, silver alloy urinary catheters may provide both clinical

and economic benefits in patients receiving indwelling catheterization for 2 to 10 days.3

 It should

be noted that one of the major assumptions made in the economic evaluation is that a certain

proportion of patients with bacteriuria develop the clinically important (Level 1) outcomes of

symptomatic UTI or bacteremia. The economic analysis did not assign any costs to bacteriuria

but did assign costs if patients developed these clinically important outcomes. Additionally,

several of the very recent efficacy studies of silver alloy catheters19,21,22 were not included in the

economic analysis. A clinical study, adequately powered to detect both meaningful clinical and

economic endpoints, would confirm the results of this economic evaluation that relied on

modeling techniques. The overall cost of universal implementation of silver alloy catheters is

unclear.

Comment

The data supporting the use of silver alloy urinary catheters to reduce urinary catheterrelated bacteriuria is reasonably strong. As noted, the incidence of bacteriuria, while not

extremely high, carries a high morbidity. It remains unclear whether silver alloy urinary

catheters will also lead to decreases in the clinically more important outcomes of catheter-related

bacteremia and mortality. Continuing investigation into the impact of silver alloy catheters on

these important outcomes and their effect on the emergence of antibiotic resistance should be

pursued.
152

Of note, catheters coated with antibacterial substances other than silver have also been

evaluated. A recent randomized study8

 found that patients who received antimicrobialimpregnated catheters coated with minocycline and rifampin had significantly lower rates of

gram-positive bacteriuria than a control group given standard, non-coated catheters (7.1% vs.

38.2%; p <0.001). Both control and intervention groups had similar rates of gram-negative

bacteriuria and candiduria (Table 15.1.1). However, the theoretical risk of developing

antimicrobial resistance to minocycline and/or rifampin (2 agents occasionally used

systemically) may limit the use of catheters coated with these antibiotics.
153

Table 15.1.1. Studies of silver alloy and antibiotic-impregnated urethral catheters*

Study Description Design,

Outcomes

Results: Odds or Risk of Bacteriuria†

(unless otherwise noted)

Saint,

19987

Meta-analysis of 4 randomized

controlled trials (n=453) of

silver alloy vs. uncoated urinary

catheters

Level 1A,

Level 2

OR 0.24 (95% CI: 0.11-0.52)

Maki,

199822

Prospective, randomized,

double-blind trial of silver alloy

(n=407) vs. standard Foley

(n=443) catheters

Level 1,

Level 2

RR 0.74 (95% CI: 0.56-0.99)

Prospective, randomized study

of medium-term catheterization

with silver alloy (n=18) vs.

silicone (n=17) catheters after

radical prostatectomy

Level 1,

Level 2

Verleyen, After 14 days, 50.0% vs. 53.3% (p=NS)

199918

Prospective, randomized study

of short-term catheterization

with silver alloy (n=79) vs. latex

(n=101) catheters

Level 1,

Level 2

On day 5, 6.3% vs. 11.9% (p<0.003)

Bologna,

199921

Prospective, blinded study of

silver alloy vs. standard latex

Foley catheters in 5 hospitals.

Baseline period ranged from 3-

12 months (mean, 8 months);

intervention period ranged from

7-19 months (mean, 10 months)

Level 2,

Level 1

Unadjusted infection rate: 4.5 vs. 7.1

infections per 1000 catheter days

(p<0.01)

Adjusted infection rate: 4.9 vs. 8.1

infections per 1000 catheter days

(p=0.13)

Karchmer,

200019

12-month randomized crossover

trial of catheter-associated

urinary tract infections in

patients with silver-coated and

uncoated catheters. The ward

was the unit of analysis. A cost

analysis was also conducted.

Level 1,

Level 1

Infection rate: 2.66 vs. 3.35 infections

per 1000 patient-days, RR 0.79 (95%

CI: 0.63-0.99)

Infection rate: 1.10 vs. 1.36 infections

per 100 patients, RR 0.81 (95% CI:

0.65-1.01)

Infection rate: 2.13 vs. 3.12 infections

per 100 catheters, RR 0.68 (95% CI:

0.54-0.86)

Estimated hospital cost savings with

silver-coated catheters: $14,456 to

$573,293

Thibon,

200020

Multicenter, prospective,

randomized, double-blind trial of

silver alloy (n=90) vs. standard

(n=109) catheters in patients

Level 1,

Level 2

After 10 days, 10% vs. 11.9%

OR 0.82 (95% CI, 0.30-2.20)
154

requiring catheterization for >3

days

Darouiche,

19998

Multicenter, prospective,

randomized, blinded trial of

medium-term catheterization

(mean, 14 days) with

minocycline-rifampin

impregnated (n=56) vs. silicone

(n=68) catheters after radical

prostatectomy

Level 1,

Level 2

Patients took longer to develop

bacteriuria with antimicrobialimpregnated catheters than control

catheters (p=0.006 by the log-rank

test)

Overall bacteriuria at day 7: 15.2% vs.

39.7% (p<0.05)

Overall bacteriuria at day 14: 58.5% vs.

83.5% (p<0.05)

Gram-positive bacteriuria: 7.1% vs.

38.2% (p<0.001)

Gram-negative bacteriuria: 46.4% vs.

47.1% (p=NS)

Candiduria: 3.6% vs. 2.9% (p=NS)

* CI indicates confidence interval; NS, not statistically significant; OR, odds ratio; and RR,

relative risk.

† Results are reported as intervention group (silver alloy or minocycline/rifampin catheter) vs.

control group.

References

1. Jain P, Parada JP, David A, Smith LG. Overuse of the indwelling urinary tract catheter in

hospitalized medical patients. Arch Intern Med. 1995;155:1425-1429.

2. Saint S. Clinical and economic consequences of nosocomial catheter-related bacteriuria.

Am J Infect Control. 2000;28:68-75.

3. Saint S, Veenstra DL, Sullivan SD, Chenoweth C, Fendrick AM. The potential clinical and

economic benefits of silver alloy urinary catheters in preventing urinary tract infection.

Arch Intern Med. 2000;160:2670-2675.

4. Haley RW, Hooton TM, Culver DH, Stanley RC, Emori TG, Hardison CD, et al.

Nosocomial infections in U.S. hospitals, 1975-1976: estimated frequency by selected

characteristics of patients. Am J Med. 1981;70:947-959.

5. Haley RW, Culver DH, White JW, Morgan WM, Emori TG. The nationwide nosocomial

infection rate. A new need for vital statistics. Am J Epidemiol. 1985;121:159-167.

6. Krieger JN, Kaiser DL, Wenzel RP. Urinary tract etiology of bloodstream infections in

hospitalized patients. J Infect Dis. 1983;148:57-62.

7. Saint S, Elmore JG, Sullivan SD, Emerson SS, Koepsell TD. The efficacy of silver alloycoated urinary catheters in preventing urinary tract infection: a meta-analysis. Am J Med.

1998;105:236-241.

8. Darouiche RO, Smith JA, Jr., Hanna H, Dhabuwala CB, Steiner MS, Babaian RJ, et al.

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated

bacteriuria: a prospective, randomized, multicenter clinical trial. Urology. 1999;54:976-

981.
155

9. Kunin CM. Urinary Tract Infections: Detection, Prevention, and Management. 5th ed.

Baltimore: Williams and Wilkins; 1997.

10. Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic:

a prospective study of 1,497 catheterized patients. Arch Intern Med. 2000;160:678-682.

11. Platt R, Polk BF, Murdock B, Rosner B. Mortality associated with nosocomial urinary-tract

infection. N Engl J Med. 1982;307:637-642.

12. Platt R, Polk BF, Murdock B, Rosner B. Reduction of mortality associated with

nosocomial urinary tract infection. Lancet. 1983;1:893-897.

13. Krieger JN, Kaiser DL, Wenzel RP. Nosocomial urinary tract infections: secular trends,

treatment and economics in a university hospital. J Urol. 1983;130:102-106.

14. Lundeberg T. Prevention of catheter-associated urinary-tract infections by use of silverimpregnated catheters [letter]. Lancet. 1986;2:1031.

15. Liedberg H, Lundeberg T. Silver alloy coated catheters reduce catheter-associated

bacteriuria. Br J Urol. 1990;65:379-381.

16. Liedberg H, Lundeberg T, Ekman P. Refinements in the coating of urethral catheters

reduces the incidence of catheter-associated bacteriuria. An experimental and clinical

study. Eur Urol. 1990;17:236-240.

17. Liedberg H, Lundeberg T. Prospective study of incidence of urinary tract infection in

patients catheterized with bard hydrogel and silver-coated catheters or bard hydrogelcoated catheters [abstract]. J Urol. 1993;149:405A.

18. Verleyen P, De Ridder D, Van Poppel H, Baert L. Clinical application of the Bardex IC

Foley catheter. Eur Urol. 1999;36:240-246.

19. Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM. A randomized crossover

study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med.

2000;160:3294-3298.

20. Thibon P, Le Coutour X, Leroyer R, Fabry J. Randomized multi-centre trial of the effects

of a catheter coated with hydrogel and silver salts on the incidence of hospital-acquired

urinary tract infections. J Hosp Infect. 2000;45:117-124.

21. Bologna RA, Tu LM, Polansky M, Fraimow HD, Gordon DA, Whitmore KE.

Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates

in intensive care unit patients: a multicenter study. Urology. 1999;54:982-987.

22. Maki DG, Knasinski V, Halvorson K, Tambyah PA. A novel silver-hydrogel-impregnated

indwelling urinary catheter reduces CAUTIs: a prospective double-blind trial [abstract].

Infect Control Hosp Epidemiol. 1998;19:682(A10).

23. Stark RP, Maki DG. Bacteriuria in the catheterized patient. What quantitative level of

bacteriuria is relevant? N Engl J Med. 1984;311:560-564.

24. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann

Intern Med. 1996;125:605-613.

Subchapter 15.2. Use of Suprapubic Catheters

Background

As discussed in Subchapter 15.1, the use of indwelling urethral catheters results in

substantial morbidity and mortality. Given the medical and social morbidity associated with

urethral catheters, many clinicians have considered suprapubic catheterization as an alternative
156

to catheterization via the urethra. Suprapubic catheters are inserted in the lower abdomen, an

area with less bacterial colonization than the periurethral region, so that the risk for infection is

thought to be lower than with urethral catheters. Furthermore, although the suprapubic placement

of urinary catheters represents a minor surgical procedure, patients may find the result more

comfortable89 and, as reviewed below, the development of infectious complications is reduced.

Subchapter 15.1 discusses the use of silver alloy urinary catheters. The focus of this chapter is

the use of suprapubic catheters as compared with standard urethral indwelling catheters in adults.

Practice Description

Suprapubic catheterization typically involves the percutaneous placement of a standard

urinary catheter directly into the bladder. The procedure is performed by urologists using sterile

technique. It is generally performed in the operating room and is considered minor surgery.

Prevalence and Severity of Target Problem

In addition to the infectious complications (and their associated costs) discussed in

Subchapter 15.1, the use of urethral catheters causes substantial patient discomfort. In a recent

study at a Veteran Affairs Medical Center, 42% of catheterized patients surveyed reported that

the indwelling catheter was uncomfortable, 48% complained that it was painful, and 61% noted

that it restricted their activities of daily living.7

 Restricted activity reduces patient autonomy and

may promote other nosocomial complications, such as venous thromboembolism and pressure

ulcers. In addition, 30% of survey respondents stated that the catheter’s presence was

embarrassing, and in unsolicited comments that supplemented the structured questionnaires

several noted that it “hurts like hell.”

7

Opportunities for Impact

Since catheter-related urinary tract infection (UTI) is the leading cause of nosocomial

infection in the United States and is associated with increased morbidity and costs, any

intervention that reduces the incidence of catheter-related UTI is potentially important.

Currently, it is unknown what proportion of patients who require indwelling urinary catheters

receive suprapubic catheters, however, this practice is uncommon.

Study Design

There have been twelve prospective studies,8,9,11-17 all but one randomized,15 comparing

the efficacy of suprapubic catheters with standard, non-coated catheters (Table 15.2.1). In all of

these studies, the patient was the unit of analysis. The patient populations for these studies varied

but generally included patients with acute urinary retention and those undergoing various

surgical procedures. Since most of the patients evaluated resided in acute care hospitals, the

average duration of catheterization was generally less than 14 days.

Study Outcomes

All the trials focused on the outcome of bacteriuria. Several of the studies also assessed

patient satisfaction and the incidence of mechanical complications. The definition of bacteriuria

varied somewhat in the studies. However, low-level growth from a catheterized specimen (ie,

102

 colony forming units (CFU)/mL) usually progresses within days to concentrations of greater

than 104

 CFU/mL, unless antibiotic therapy is given.18 Unfortunately, none of the studies was

adequately powered to detect a significant difference in the clinically more important outcomes

of catheter-related bacteremia or death. Though bacteriuria is a surrogate endpoint,19 it is
157

probably appropriate to use since it is a component of the only causal pathway in the disease

process between suprapubic catheterization and an important clinical outcome (eg, symptomatic

UTI or catheter-related bacteremia).

Evidence for Effectiveness of the Practice

As shown in Table 15.2.1, studies comparing suprapubic catheterization with urethral

catheterization have produced mixed results.8,9,11-17,20-22 Six trials reported lower rates of

bacteriuria in patients with suprapubic catheters,11,13,15,16,21,22 and 4 trials indicated greater patient

satisfaction with suprapubic as opposed to urethral catheters.8,13,16,20 In 3 of the studies, however,

mechanical complications were higher in those receiving suprapubic catheters.12,15,16 Of note, 3

studies found that patients given suprapubic catheters have significantly decreased incidence of

urethral strictures compared with patients who received urethral catheters.15,23,24 However, the

use of prophylactic antibiotics in patients receiving urethral catheters for transurethral resection

of the prostate has been shown to significantly reduce the incidence of strictures in the anterior

urethra.25

Potential for Harm

As stated above, the primary problem associated with suprapubic catheter use involves

mechanical complications associated with insertion, most commonly catheter dislodgement or

obstruction, and failed introduction. The safe insertion of suprapubic indwelling urinary

catheters depends on trained personnel.

Costs and Implementation

The cost of each suprapubic urinary catheter tray is comparable to the cost of each

standard, non-coated urethral catheter tray. However, the overall initial costs of using suprapubic

catheters will no doubt be greater since procedure-related costs are substantially higher for

suprapubic than urethral catheters. Nurses are able to place urethral catheters at the bedside, but

urologists must place suprapubic catheters, and the procedure typically occurs in the operating

room. Additionally, it is unclear whether urologists are currently proficient at the insertion of

suprapubic catheters given how infrequently they are used. If suprapubic catheters are shown to

be effective, they may have a positive impact on patient care. The cost of training individuals in

inserting and maintaining the suprapubic catheter is likely to be substantial.

Comment

When compared with standard urethral indwelling catheters, suprapubic urinary catheters

may reduce urinary catheter-related bacteriuria. Additionally, patient satisfaction may be greater

with suprapubic catheters, although there is also evidence that patients placed with suprapubic

catheters more frequently experience certain mechanical complications. On the other hand,

urethral catheters are likely to lead to a higher incidence of urethral strictures. Given these mixed

results, conclusions regarding the overall benefit of routine suprapubic catheterization cannot

currently be made. However, it would be reasonable to consider conducting a formal metaanalysis of the published trials to answer the question, “Compared with urethral indwelling

catheters, are suprapubic catheters less likely to lead to UTI (as measured by bacteriuria) and

more likely to lead to enhanced patient satisfaction?” Using explicit inclusion criteria and

accepted quantitative methods, a meta-analysis26-28 can often help clarify the features of

individual studies that have divergent results.29 In addition, a possible interaction between gender

of the patient and type of catheter is of interest since different pathophysiologic mechanisms
158

underlie the development of urethral catheter-related infection in men and women.30 The

possibility of adequately evaluating effects within subgroups (eg, those undergoing certain

surgical procedures) because of an increased sample size is one of the benefits of metaanalysis.31

If formal meta-analysis suggests that suprapubic catheters are less likely to lead to

urinary tract infection and more likely to enhance patient satisfaction, at least in some clinical

settings, then these catheters should be considered in the management of certain patients. On the

other hand, if the meta-analysis finds that urethral catheters are superior to suprapubic catheters,

then use of suprapubic catheters, albeit currently quite limited, should be further reduced.
159

Table 15.2.1. Prospective studies comparing suprapubic with urethral catheters

Study Design, Bacteriuria (%)†

Outcomes

Patient

Population* Suprapubic Urethral

Odds Ratio

(95% CI)‡

Comments§

Shapiro,

198216

Level 1,

Level 2

General

surgical

patients with

urinary

retention

2/25 (8) 21/31

(68)

0.04

(0.01-0.24)

Pseudorandomized (urethral

catheters used in every third

patient) study; suprapubic

group had less pain but more

mechanical complications

Andersen,

198513

Level 1,

Level 2

Women

undergoing

vaginal

surgery

10/48 (21) 20/44

(45)

0.32

(0.11-0.86)

Patients rated acceptability of

suprapubic catheters greater

Ichsan,

19879

Level 1,

Level 2

Patients with

acute urinary

retention

3/29 (10) 11/37

(30)

0.27

(0.04-1.22)

None of the suprapubic group

complained of discomfort

compared with 17 of the

patients given urethral

catheters

Sethia,

198711

Level 1,

Level 2

General

surgical

patients

requiring

urine output

monitoring

2/32 (6) 16/34

(47)

0.08

(0.01-0.41)

Decrease in bacteriuria was

more significant in women

than in men

Schiotz,

198912

Level 1,

Level 2

Women

undergoing

vaginal

surgery

8/38 (21) 5/40

(12)

1.87

(0.48-8.01)

26% of suprapubic group

versus 5% of urethral group

had mechanical

complications

Horgan,

199215

Level 2,

Level 2

Men with

acute urinary

retention due

to prostatic

enlargement

10/56 (18) 12/30

(40)

0.33

(0.11-0.99)

21% of suprapubic group

versus 3% of urethral group

had dislodgement; 0% of

suprapubic group versus 17%

of urethral group developed

urethral strictures

O’Kelley,

19958

Level 1,

Level 2

General

surgical

patients

requiring

abdominal

surgery

3/28 (11) 3/29

(10)

1.04

(0.13-8.51)

Study design unclear, but

probably not randomized;

suprapubic catheters caused

significantly fewer days of

catheter-related pain

Ratnaval,

199614

Level 1,

Level 2

Men

undergoing

colorectal

surgery

1/24 (4) 3/26

(12)

0.33

(0.01-4.60)

Suprapubic group had fewer

voiding difficulties
160

Bergman,

198721

Level 1,

Level 2

Women

undergoing

vaginal

surgery for

stress

incontinence

4/24 (17) 17/27

(63)

0.26

(0.10-0.68)

Length of hospital stay was

significantly less (by 1 day)

in the suprapubic catheter

group

Abrams,

198020

Level 1,

Level 2

Men with

urinary

retention

21/52 (40) 13/50

(26)

1.6

(0.88-2.75)

12% of suprapubic catheter

group found catheter

uncomfortable compared with

64% in the standard urethral

catheter group (p<0.001)

Vandoni,

199422

Level 1,

Level 2

Patients

requiring

surgery for

various

indications

0/19 (0) 6/24

(25)

0

(0-0.95)

All patients given precatheterization antibiotics;

slight decrease in pain and

discomfort in suprapubic

group but not significant

(authors do not provide actual

satisfaction data)

Perrin,

199717

Level 1,

Level 2

Patients

undergoing

rectal surgery

12/49 (24) 29/59

(49)

0.34

(0.13-0.83)

12% of suprapubic group

reported catheter discomfort

compared with 29% of

urethral group

* Studies enrolled both men and women unless otherwise noted.

†Indicates the ratio of patients who developed bacteriuria to the total number of participants

assigned to each group.

‡ Odds of developing bacteriuria in the suprapubic versus urethral catheter groups; CI indicates

confidence interval.

§ Mechanical complications consisted of failed introduction of catheter, and catheter dislodgement

or obstruction.

References

1. Kunin CM. Urinary Tract Infections: Detection, Prevention, and Management. 5th ed.

Baltimore: Williams and Wilkins; 1997.

2. Saint S. Clinical and economic consequences of nosocomial catheter-related bacteriuria.

Am J Infect Control 2000;28:68-75.

3. Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic:

a prospective study of 1,497 catheterized patients. Arch Intern Med 2000;160:678-82.

4. Platt R, Polk BF, Murdock B, Rosner B. Mortality associated with nosocomial urinary-tract

infection. N Engl J Med 1982;307:637-642.

5. Platt R, Polk BF, Murdock B, Rosner B. Reduction of mortality associated with

nosocomial urinary tract infection. Lancet 1983;1:893-897.
161

6. Saint S, Veenstra DL, Sullivan SD, Chenoweth C, Fendrick AM. The potential clinical and

economic benefits of silver alloy urinary catheters in preventing urinary tract infection.

Arch Intern Med 2000;160:2670-2675.

7. Saint S, Lipsky BA, Baker PD, McDonald LL, Ossenkop K. Urinary catheters: What type

do men and their nurses prefer? J Am Geriatr Soc 1999;47:1453-1457.

8. O'Kelly TJ, Mathew A, Ross S, Munro A. Optimum method for urinary drainage in major

abdominal surgery: a prospective randomized trial of suprapubic versus urethral

catheterization. Br J Surg 1995;82:1367-1368.

9. Ichsan J, Hunt DR. Suprapubic catheters: a comparison of suprapubic versus urethral

catheters in the treatment of acute urinary retention. Aust N Z J Surg 1987;57:33-36.

10. Krieger JN, Kaiser DL, Wenzel RP. Nosocomial urinary tract infections: secular trends,

treatment and economics in a university hospital. J Urol 1983;130:102-106.

11. Sethia KK, Selkon JB, Berry AR, Turner CM, Kettlewell MG, Gough MH. Prospective

randomized controlled trial of urethral versus suprapubic catheterization. Br J Surg

1987;74:624-625.

12. Schiotz HA, Malme PA, Tanbo TG. Urinary tract infections and asymptomatic bacteriuria

after vaginal plastic surgery. A comparison of suprapubic and transurethral catheters. Acta

Obstet Gynecol Scand 1989;68:453-455.

13. Andersen JT, Heisterberg L, Hebjorn S, Petersen K, Stampe Sorensen S, Fischer

Rasmussen W, et al. Suprapubic versus transurethral bladder drainage after

colposuspension/vaginal repair. Acta Obstet Gynecol Scand 1985;64:139-143.

14. Ratnaval CD, Renwick P, Farouk R, Monson JR, Lee PW. Suprapubic versus transurethral

catheterisation of males undergoing pelvic colorectal surgery. Int J Colorectal Dis

1996;11:177-179.

15. Horgan AF, Prasad B, Waldron DJ, O'Sullivan DC. Acute urinary retention. Comparison of

suprapubic and urethral catheterisation. Br J Urol 1992;70:149-151.

16. Shapiro J, Hoffmann J, Jersky J. A comparison of suprapubic and transurethral drainage for

postoperative urinary retention in general surgical patients. Acta Chir Scand 1982;148:323-

327.

17. Perrin LC, Penfold C, McLeish A. A prospective randomized controlled trial comparing

suprapubic with urethral catheterization in rectal surgery. Aust N Z J Surg 1997;67:554-

556.

18. Stark RP, Maki DG. Bacteriuria in the catheterized patient. What quantitative level of

bacteriuria is relevant? N Engl J Med 1984;311:560-564.

19. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann

Intern Med 1996;125:605-613.

20. Abrams PH, Shah PJ, Gaches CG, Ashken MH, Green NA. Role of suprapubic

catheterization in retention of urine. J R Soc Med 1980;73:845-848.

21. Bergman A, Matthews L, Ballard CA, Roy S. Suprapubic versus transurethral bladder

drainage after surgery for stress urinary incontinence. Obstetrics & Gynecology

1987;69:546-549.

22. Vandoni RE, Lironi A, Tschantz P. Bacteriuria during urinary tract catheterization:

suprapubic versus urethral route: a prospective randomized trial. Acta Chir Belg

1994;94:12-16.

23. Hammarsten J, Lindqvist K, Sunzel H. Urethral strictures following transurethral resection

of the prostate. The role of the catheter. Br J Urol 1989;63:397-400.
162

24. Hammarsten J, Lindqvist K. Suprapubic catheter following transurethral resection of the

prostate: a way to decrease the number of urethral strictures and improve the outcome of

operations. J Urol 1992;147:648-651.

25. Hammarsten J, Lindqvist K. Norfloxacin as prophylaxis against urethral strictures

following transurethral resection of the prostate: an open, prospective, randomized study. J

Urol 1993;150:1722-1724.

26. Yusuf S. Obtaining medically meaningful answers from an overview of randomized

clinical trials. Stat Med 1987;6:281-294.

27. Light RJ. Accumulating evidence from independent studies: what we can win and what we

can lose. Stat Med 1987;6:221-231.

28. Hennekens CH, Buring JE, Hebert PR. Implications of overviews of randomized trials. Stat

Med 1987;6:397-409.

29. Sacks HS, Berrier J, Reitman D, Ancona Berk VA, Chalmers TC. Meta-analyses of

randomized controlled trials. N Engl J Med 1987;316:450-455.

30. Daifuku R, Stamm WE. Association of rectal and urethral colonization with urinary tract

infection in patients with indwelling catheters. JAMA 1984;252:2028-2030.

31. Gelber RD, Goldhirsch A. Interpretation of results from subset analyses within overviews

of randomized clinical trials. Stat Med 1987;6:371-388.
163

Chapter 16. Prevention of Intravascular Catheter-Associated Infections

Sanjay Saint, MD, MPH

University of Michigan School of Medicine

Background

Central venous catheters inserted for short-term use have become common and important

devices in caring for hospitalized patients, especially the critically ill.1

 While they have

important advantages (eg, ability to administer large volumes of fluid), short-term vascular

catheters are also associated with serious complications, the most common of which is infection.

Intravascular catheters are one of the most common causes of nosocomial bacteremia;2

 and

catheter-related bloodstream infection (CR-BSI) affects over 200,000 patients per year in the

United States.3

 This chapter focuses primarily on short-term central venous catheters. Two

relatively recent reviews address prevention of infection due to other types of vascular

catheters.4,5 We review use of maximum barrier precautions (Subchapter 16.1), central venous

catheters coated with antibacterial or antiseptic agents (Subchapter 16.2), and use of

chlorhexidine gluconate at the insertion site (Subchapter 16.3). We review several promising

practices, as well as some common ineffective practices (Subchapter 16.4).

Definitions and Microbiology

Catheter-related infections can be subdivided into those that are local and those that are

bacteremic. Local infection involves only the insertion site and manifests as pericatheter skin

inflammation. Local infection is usually diagnosed when there is evidence of an insertion-site

infection (eg, purulence at the exit site). Catheter colonization is defined by growth of an

organism from the tip or the subcutaneous segment of the removed catheter. Growth of greater

than 15 colony-forming units (CFU) using the semiquantitative roll-plate culture technique is

often used to define catheter colonization.6

 Alternatively, the presence of more than 1000 CFUs

per catheter tip segment by quantitative culture using a method such as sonication indicates

evidence of catheter colonization.7

 Signs of local infection may or may not be present when there

is significant catheter colonization; evidence of local infection is observed in at least 5% of

patients with catheter colonization.

Bacteremic catheter-related infection (often also referred to as CR-BSI) is defined as a

positive blood culture with clinical or microbiologic evidence that strongly implicates the

catheter as the source of infection.1

 This includes: 1) evidence of local infection with isolation of

the same organism from both pus around the site and bloodstream; or 2) positive cultures of both

the catheter tip (using either semi-quantitative or quantitative methods) and bloodstream with the

same organism; or 3) clinical evidence of sepsis (eg, fever, altered mental status, hypotension,

leukocytosis) that does not respond to antibiotic therapy, but resolves once the catheter is

removed.1,5 Some have proposed additional methods of diagnosing CR-BSI, including paired

blood cultures (drawn from both the central venous catheter and from a noncatheterized vein)8

and a technique in which time to culture positivity for blood drawn from the central venous

catheter is compared with that for the blood drawn from percutaneous venipuncture.9

The most common organisms causing catheter-related infections are staphylococci, gram

negative rods, and Candida species.10,11 The pathophysiology of these infections include several

mechanisms, the most important of which involve the skin insertion site and the catheter hub.1

Bacteria migrate from the insertion site on the skin along the external surface of the catheter and
164

then colonize the distal tip.12,13 The hub can also lead to infection when bacteria are introduced

via the hands of medical personnel. These organisms then migrate along the internal surface of

the lumen and may result in bacteremia.14

Less commonly, catheter-related infection can result from hematogenous seeding of the

catheter from another focus15 or from contaminated infusates.16

Prevalence and Severity of the Target Safety Problem

A recent quantitative review found that of patients in whom standard, non-coated central

venous catheters are in place on average for 8 days, 25% can be expected to develop catheter

colonization and 5% will develop CR-BSI.17 The risk of CR-BSI from this estimate is similar to

the rate reported by the Federal Centers for Disease Control and Prevention (CDC). The CDC

has reported an average CR-BSI rate of 2.8 to 12.8 infections per 1000 catheter-days for all types

of intensive care units and average rates of 4.5 to 6.1 infections per 1000 catheter-days for

medical/surgical intensive care units.18

CR-BSI is associated with an increased risk of dying, but whether this association is

causal remains controversial.17 Some argue that hospitalized patients who develop CR-BSI may

differ in their clinical and physiologic characteristics, and thus may have a higher risk of dying

due to intrinsic factors. Proponents of this view believe that the development of CR-BSI is

primarily a marker of severe underlying disease or deficient immunity rather than an

independent risk factor for dying. Unfortunately, the few studies evaluating attributable mortality

due to CR-BSI have conflicting results.

Pittet and colleagues estimated that the attributable mortality of CR-BSI was 25% in a

matched case-control study.19,20 Another matched study estimated that the attributable mortality

was 28%.21 Other investigators have found a much smaller attributable mortality associated with

CR-BSI. DiGiovine et al, in a matched case-control study of 136 medical intensive care unit

patients, found a non-significant attributable mortality of CR-BSI (4.4%; p=0.51).22 A recent,

carefully matched cohort study of 113 patients by Soufir and colleagues also failed to detect a

statistically significant increase in mortality associated with CR-BSI.23 Nevertheless, given the

small sample size, these authors concluded that their findings are consistent with a 10% to 20%

increased mortality due to CR-BSI.23 Further research to clarify the mortality associated with

CR-BSI is needed, but the available data are consistent with an attributable mortality of CR-BSI

ranging between 4% and 20%.

Central venous catheter related infection also leads to increased health care costs. Though

there is substantial variability in the economic estimates, a recent review estimates that an

episode of local catheter-related infection leads to an additional cost of approximately $400,

while the additional cost of CR-BSI ranges from about $6005 to $9738.17 Some have estimated

that each episode leads to even higher costs, approximately $25,000 per episode.19,20
165

Prevention

Unnecessarily prolonged catheterization should be avoided. Because of the increased risk

of infection with prolonged catheterization, many clinicians attempt to reduce this risk with

routine changes of the catheter, either over a guidewire or with a new insertion site. However,

the available data do not support this practice.24 Eyer et al25 randomized 112 surgical patients

receiving a central venous, pulmonary arterial, or systemic arterial catheter for more than 7 days

into three groups: a) weekly catheter change at a new site; or b) weekly guidewire exchange at

the same site; or c) no routine weekly changes. No significant difference was noted in the

incidence of local or bacteremic infection.25 Cobb and colleagues26 randomized 160 patients with

central venous or pulmonary arterial catheters to either replacement every 3 days at a new site or

over a guidewire, or replacement only when clinically indicated. In those with replacement

catheters at new sites, the risk of infectious complications was not decreased and the number of

mechanical complications was increased. Those undergoing routine replacement via a guidewire

exchange showed a trend towards a higher rate of bloodstream infections compared with those

who had catheter replacement only when clinically indicated.26 A recent meta-analysis has

confirmed that routine changes of central venous and systemic arterial catheters appear

unnecessary;24 attempts should be made, however, to limit the duration of catheterization. Strict

adherence to proper handwashing and use of proven infection control principles is crucial (see

Chapters 13 and 14).27,28

Subchapter 16.1. Use of Maximum Barrier Precautions During Central Venous Catheter

Insertion

Practice Description

Catheter-related infections often result from contamination of the central venous catheter

during insertion. Maximum sterile barrier (MSB) precautions may reduce the incidence of

catheter contamination during insertion and thus reduce the rate of CR-BSI. MSB precautions

consist of the use of sterile gloves, long-sleeved gowns, and a full-size drape as well as a nonsterile mask (and often a non-sterile cap) during central venous catheter insertion.

Opportunities for Impact

The proportion of patients receiving central venous catheters in whom maximum barrier

precautions are employed is not currently known. If maximum barrier precautions are not used,

then the standard insertion technique involves the use of only sterile gloves and a sterile small

drape. Given the additional time required to employ MSB, it is likely that many patients are not

receiving maximum barrier precautions during catheter insertion.

Study Designs

One randomized and one non-randomized study have evaluated the use of maximum

barrier precautions (Table 16.1.1). The clinical trial randomized 176 patients to catheter insertion

using MSB and 167 patients to control (use of sterile gloves and sterile small drape).29 A nonrandomized before-after observational evaluation assessed the effect of a 1-day course on

infection control practices and procedures on physician compliance with MSB use and incidence

of catheter-infection.30
166

Study Outcomes

Both studies evaluated rates of catheter-related infection (Level 1), including local and

bloodstream infection.

Evidence for Effectiveness of the Practice

There is moderately strong evidence that use of maximum barrier precautions decrease

the risk of catheter-related infection (Table 16.1.1). Furthermore, the evidence that health care

providers—specifically physicians-in-training—can be taught proper use of barrier precautions

and thereby decrease the incidence of infection is reasonably strong.

Potential for Harm

There is virtually no harm associated with this intervention.

Costs and Implementation

The use of maximum barrier precautions will cost more than not using this technique in

both materials and time. Additionally, teaching health care providers how to properly use

maximum barrier precautions is also time-consuming and expensive. Sherertz and colleagues

estimated the overall cost of their educational program and supplies to be $74,081.30 However,

when the costs of preventing catheter-related infection are also included, use of MSB has been

estimated to be cost-saving in simplified “back-of-the-envelope” cost studies.29,30 Formal

economic evaluation is required to fully assess the economic consequences of full adoption of

maximum barrier precautions.

Comments

Use of MSB appears to be a reasonable method of preventing catheter-related infection.

Though achieving full compliance with this method of catheter insertion is likely to be

challenging, a relatively simple educational intervention has demonstrated effectiveness in

improving adherence and reducing infection rates. Given the excellent benefit-to-harm ratio of

this patient safety practice, it seems reasonable to strongly consider employing MSB for all

patients requiring central venous catheters. The economic consequences of full implementation

of this practice are still not entirely clear.
167

Table 16.1.1. Studies of vascular catheter-related infection*

Study Description; Intervention Study

Design,

Outcomes

Results (p-value or 95% CI)†

343 patients in a 500-bed cancer referral

center; catheters inserted under maximal

sterile barrier precautions (mask, cap,

sterile gloves, gown, and large drape)

vs. control precautions (sterile gloves

and small drape only)29

Level 1,

Level 1

CR-BSI per 1000 catheter days: 0.08

vs. 0.5, (p=0.02)

Catheter colonization: 2.3% vs. 7.2%

(p=0.04)

6 ICUs and a step-down unit in an

academic medical center in NC; 1-day

course for physicians-in-training on the

control of vascular catheter infection,

emphasizing use of full-size sterile

drapes30

Level 2‡,

Level 1

Primary bloodstream infection and

catheter-related infection decreased

28% (p<0.01)

Use of full-size sterile drapes increased

from 44% to 65% (p<0.001)

Meta-analysis of 12 RCTs (2611

catheters) comparing central venous

catheters coated with

chlorhexidine/silver sulfadiazine with

standard, non-coated catheters44

Level 1A,

Level 1

Odds of CR-BSI with

chlorhexidine/silver sulfadiazine

catheter vs. standard catheter: OR

0.56 (0.37-0.84)

High-risk adult patients at 12 universityaffiliated hospitals in whom central

venous catheters were expected to

remain in place for • 3 days;

minocycline/rifampin vs.

chlorhexidine/silver sulfadiazine

catheters46

Level 1,

Level 1

Incidence of CR-BSI:

minocycline/rifampin 0.3% vs.

chlorhexidine/silver sulfadiazine

3.4% (p<0.002)

Both types of catheters had similar

efficacy for approximately the first

10 days

Meta-analysis of 7 RCTs (772 catheters)

comparing tunneling with standard

placement of short-term central venous

catheters61

Level 1A,

Level 1

Catheter-related septicemia: RR 0.56

(0.31-1); excluding 1 study of

placement in internal jugular: RR

0.71 (0.36-1.43)

Catheter colonization: RR 0.61 (0.39-

0.95); excluding 1 study of

placement in internal jugular: RR

0.59 (0.32-1.10)

Meta-analysis of 12 RCTs comparing

prophylactic heparin use (in different

forms) with no heparin use on the

following outcomes: central venous

catheter colonization (3 trials), CR-BSI

(4 trials), and catheter-related deep

venous thrombosis (7 trials)59

Level 1A,

Level 1

CR-BSI: RR 0.26 (0.07-1.03)

Catheter colonization: RR 0.18 (0.06-

0.60)

Catheter-related deep venous

thrombosis:

RR 0.43 (0.23-078)
168

Meta-analysis of 12 RCTs (918 patients,

• 1913 catheters) assessing the effect of

guidewire exchange and a prophylactic

replacement strategy (change every 3

days) on central venous catheter-related

colonization (8 trials), exit site infection

(4 trials), bacteremia (8 trials), and

mechanical complications (9 trials) in

critically ill patients24

Level 1A,

Level 1

Catheter colonization: RR 1.26 (0.87-

1.84)

Exit site infection: RR 1.52 (0.34-6.73)

Bacteremia: RR 1.72 (0.89-3.33)

Mechanical complications: RR 0.48

(0.12-1.91)

Prophylactic catheter replacement

every 3 days was not found to be

better than as-needed replacement

* CI indicates confidence interval; CR-BSI, catheter-related bloodstream infection; OR, odds

ratio; RCT, randomized controlled trial; and RR, relative risk.

†Results are reported as intervention group vs. control (standard or usual care) group.

‡ Prospective before-after study design.
169

Subchapter 16.2. Use of Central Venous Catheters Coated with Antibacterial or

Antiseptic Agents

Practice Description

Recent studies have indicated that central venous catheters coated with antimicrobial

agents reduce the incidence of catheter-related bloodstream infection (CR-BSI). Implementing

use of these catheters would be simple, primarily involving the replacement of standard, noncoated vascular catheters. However, these catheters, such as chlorhexidine/silver sulfadiazineimpregnated catheters and minocycline/rifampin-coated catheters, are more expensive than

standard catheters. Thus, the cost-effectiveness of these catheters needs to be considered by

decision makers.

Opportunities for Impact

Currently, it is not known precisely what proportion of patient who require central

venous catheterization receive an antimicrobial catheter, however, it is probably the minority of

patients.

Study Designs

Multiple randomized trials have compared chlorhexidine/silver sulfadiazine central

venous catheters with standard, non-coated central venous catheters.31-43 In addition, a recent

meta-analysis used a fixed effects model to combine the results of these chlorhexidine/silver

sulfadiazine trials.44 A large, multicenter study has compared minocycline/rifampin coated

catheters with non-coated, standard catheters.45 Additionally, a recent multicenter randomized

trial of minocycline/rifampin versus chlorhexidine/silver sulfadiazine catheters has also been

reported.46 The majority of the patients enrolled in the individual studies cited above had a

central venous catheter in place for 8 days on average (range of average duration, 5 to 11 days).

Details of the characteristics and results of the trials comparing central venous catheters coated

with chlorhexidine/silver sulfadiazine to control catheters are in Tables 16.2.1 and 16.2.2.

Study Outcomes

Most studies reported the incidence of catheter colonization and CR-BSI. Though the

precise outcome definitions in some of the studies varied, in general the definition of catheter

colonization and CR-BSI used in most of these studies was explicit and appropriate.

Evidence for Effectiveness of the Practice

The evidence for the efficacy of chlorhexidine/silver sulfadiazine catheters is fairly

substantial. The recent meta-analysis found a statistically significant decrease in the incidence of

CR-BSI (odds ratio 0.56, 95% CI: 0.37-0.84).44 There is also reasonable evidence that

minocycline-rifampin catheters reduce the risk of CR-BSI compared with standard, non-coated

catheters. The recent randomized trial of minocycline/rifampin versus chlorhexidine/silver

sulfadiazine catheters found a significant and clinically important decrease in the incidence of

CR-BSI in the group of patients using minocycline/rifampin compared with chlorhexidine/silver

sulfadiazine catheters (0.3% vs. 3.4%, p<0.002).46 Of note, both types of coated catheters had

similar efficacy for approximately the first 10 days of catheterization.

Potential for HarmThe potential for occurrence of immediate hypersensitivity reaction

in association with the use of chlorhexidine/silver sulfadiazine impregnated catheters is of
170

concern. Although there have been no reports of hypersensitivity reactions to

chlorhexidine/silver sulfadiazine impregnated central venous catheters in the United States (out

of more than 2.5 million sold), 13 cases of immediate hypersensitivity reactions have been

reported in Japan, including one potentially associated death.47 There were 117,000 antisepticimpregnated catheters sold in Japan before their use was halted because of these cases.47 It is not

clear why there have been no reports of hypersensitivity reactions in the U.S; this heterogeneity

may be caused by a higher previous exposure of patients in Japan to chlorhexidine or by a

genetic predisposition.

Minocycline and rifampin are both occasionally used as systemic antimicrobial agents;

thus, their use on catheters raises the important theoretical issue of increased antimicrobial

resistance. At this time, there has been no conclusive evidence that antimicrobial resistance has

or will increase due to the use of these catheters.

Costs and Implementation

Formal and informal economic analyses indicate that central venous catheters coated with

antibacterial agents (such as chlorhexidine/silver sulfadiazine or minocycline/rifampin) are likely

to lead to both clinical and economic advantages in selected patients. In terms of formal

economic comparisons, a recent analysis compared chlorhexidine/silver sulfadiazine catheters to

standard catheters and found that chlorhexidine/silver sulfadiazine catheters lead to both clinical

and economic advantages in patients receiving central venous catheterization for 2 to 10 days

and who were considered high risk for infection (ie, critically ill or immunocompromised

patients). Specifically, the chlorhexidine/silver sulfadiazine catheters led to a significant decrease

in the incidence of CR-BSI and death, and a cost savings of approximately $200 per catheter

used.47 Importantly, the risk of hypersensitivity reaction to the chlorhexidine/silver sulfadiazine

catheters was considered in the analysis, but had little effect on the overall clinical and economic

outcomes.47

However, given the recently demonstrated efficacy of the minocycline/rifampin catheter

compared with the chlorhexidine/silver sulfadiazine catheter,46 a formal cost-effectiveness

analysis comparing these two types of coated catheters is necessary. This is especially important

since the minocycline/rifampin catheter costs about $9 more per catheter than the

chlorhexidine/silver sulfadiazine catheter.

Implementation of either of these catheters would be straightforward. Stocking the

appropriate antimicrobial catheter in areas of the hospital that are likely to require such catheters

(eg, intensive care unit, operative room, hematology-oncology floor) would be a relatively

simple way of translating the research findings into actual practice.
171

Comment

In light of the substantial clinical and economic burden of catheter-related infection,

hospital personnel should adopt proven cost-effective methods to reduce this common and

important nosocomial complication. The bulk of the evidence supports the use of either

chlorhexidine/silver sulfadiazine or minocycline/rifampin central venous catheters rather than

standard (non-coated) catheters in high-risk patients requiring short-term central venous

catheterization (eg, for 2 to 10 days). Choosing between the 2 antimicrobial catheters requires a

formal cost-effectiveness analysis since the minocycline/rifampin catheter costs significantly

more than the chlorhexidine/silver sulfadiazine catheter. There are 2 primary issues that should

be addressed when comparing these catheters: the expected duration of catheterization and the

risk of antibiotic resistance to the patient, the hospital, and society. Though each

minocycline/rifampin catheter costs more than the chlorhexidine/silver sulfadiazine catheter,

using minocycline/rifampin catheters may actually result in cost-savings for at least some patient

populations given their improved overall efficacy. Of note, the improved efficacy of the

minocycline/rifampin catheters may be a result of coating both the internal and external surfaces

with these substances; the chlorhexidine/silver sulfadiazine catheters evaluated to date have only

had the external surface coated with the antiseptic combination.
172

Table 16.2.1. Characteristics of trials comparing central venous catheters coated with

chlorhexidine/silver sulfadiazine to control catheters*

Study Description Number of

Catheters

(Treatment,

Control)

Mean Catheter

Duration in

Days

(Treatment,

Control)

Catheter

Colonization†

CatheterRelated

Bloodstream

Infection†

Tennenberg31: 282 hospital patients

(137 treatment, 145 control) in

variety of settings; double- and

triple-lumen catheters without

exchanges over guidewires

137,

145

5.1,

53

SQ (IV, SC,

>15 CFU)

SO (IV, SC,

site), CS, NS

Maki32: 158 ICU patients (72

treatment, 86 control); triple-lumen

catheters with catheter exchanges

over guidewires

208,

195

6.0,

6.0

SQ (IV, >15

CFU)

SO (>15 CFU,

IV, hub, inf)‡

van Heerden33§: 54 ICU patients (28

treatment, 26 control); triple-lumen

catheters without catheter exchanges

over guidewires

28,

26

6.6,

6.8

SQ (IV, >15

CFU)

NR

Hannan34: ICU patients; triple-lumen

catheters

68,

60

7,

8

SQ (IV, >103

CFU) ¶

SO (IV, >103

CFU), NS

Bach35§: 26 ICU patients (14

treatment, 12 control); triple-lumen

catheters without catheter exchanges

over guidewires

14,

12

7.0,

7.0

QN (IV, >103

CFU)

NR

Bach36§: 133 surgical patients (116

treatment, 117 control); double- and

triple-lumen cathetes without

exchanges over guidewires

116,

117

7.7,

7.7

QN (IV, >103

CFU)

SO (IV)

Heard37§: 111 SICU patients (107

treatment, 104 control); triple-lumen

catheters with exchanges over

guidewires

151,

157

8.5,

9

SQ (IV, SC,

>14 CFU)

SO (IV, SC,

>4 CFU)

Collin38: 119 ER/ICU patients (58

treatment, 61 control); single-,

double-, and triple-lumen catheters

with exchanges over guidewires

98,

139

9.0,

7.3

SQ (IV, SC,

>15 CFU)

SO (IV, SC)

Ciresi39§: 191 patients receiving

TPN (92 treatment, 99 control);

triple-lumen catheters with

exchanges over guidewires

124,

127

9.6,

9.1

SQ (IV, SC,

>15 CFU)

SO (IV, SC)

Pemberton40: 72 patients receiving

TPN (32 treatment, 40 control);

triple-lumen catheters without

exchanges over guidewires

32,

40

10,

11

NR SO (IV), Res,

NS
173

Ramsay41§: 397 hospital patients

(199 treatment, 189 control) in a

variety of settings; triple-lumen

catheters without exchanges over

guidewires

199,

189

10.9,

10.9

SQ (IV, SC,

>15 CFU)

SO (IV, SC)

Trazzera42§: 181 ICU/BMT patients

(99 treatment, 82 control); triplelumen catheters with exchanges over

guidewires

123,

99

11.2,

6.7

SQ (IV, >15

CFU)

SO (IV, >15

CFU)

George43: Transplant patients; triplelumen catheters without exchanges

over guidewires

44,

35

NR SQ (IV, >5

CFU)

SO (IV)

* BMT indicates bone marrow transplant; CFU, colony forming units; CS, clinical signs of

systemic infection; ER, emergency room; ICU, intensive care unit; IV, intravascular catheter

segment; inf, catheter infusate; NR, not reported; NS, no other sources of infection; QN,

quantitative culture; Res, resolution of symptoms upon catheter removal; SC, subcutaneous

catheter segment; SICU, surgical intensive care unit; site, catheter insertion site; SO, same

organism isolated from blood and catheter; SQ, semi-quantitative culture; and TPN, total

parenteral nutrition.

† Catheter segments (or site) cultured and criteria for a positive culture are given in parenthesis

‡ Organism identity confirmed by restriction-fragment subtyping

§ Additional information provided by author (personal communications, 1/98-3/98)

¶ Culture method reported as semiquantitative; criteria for culture growth suggests quantitative

method
174

Table 16.2.2. Results of trials comparing central venous catheters coated with

chlorhexidine/silver sulfadiazine to control catheters*

Catheter Colonization Catheter-related Bloodstream Infection

No. (%) Positive No. (%) Positive

Study

Treatment Control

Odds Ratio

(95% CI)

Treatment Control

Odds Ratio

(95% CI)

Tennenberg31 8 (5.8%) 32 (22.1%) 0.22 (0.10-0.49) 5 (3.6%) 9 (6.2%) 0.57 (0.19-1.75)

Maki32 28 (13.5%) 47 (24.1%) 0.49 (0.29-0.82) 2 (1.0%) 9 (4.6%) 0.20 (0.04-0.94)

van Heerden33† 4 (14.3%) 10 (38.5%) 0.27 (0.07-1.00) –––

Hannan34 22 (32.4%) 22 (36.7%) 0.83 (0.40-1.72) 5 (7.4%) 7 (11.7%) 0.60 (0.18-2.00)

Bach35† 0 (0%) 4 (33.3%) 0 (0-0.65) –––

Bach36† 2 (1.7%) 16 (13.7%) 0.11 (0.02-0.49) 0 (0%) 3 (2.6%) 0 (0-1.28)

Heard37 † 60 (39.7%) 82 (52.2%) 0.60 (0.38-0.95) 5 (3.3%) 6 (3.8%) 0.86 (0.26-2.89)

Collin38 2 (2.0%) 25 (18.0%) 0.10 (0.02-0.41) 1 (1.0%) 4 (2.9%) 0.35 (0.04-3.16)

Ciresi39† 15 (12.1%) 21(16.5%) 0.69 (0.34-1.42) 13 (10.5%) 14 (11.0%) 0.95 (0.43-2.10)

Pemberton40 – –– 2 (6.3%) 3 (7.5%) 0.82 (0.13-5.24)

Ramsay41† 45 (22.6%) 63 (33.3%) 0.58 (0.37-0.92) 1 (0.5%) 4 (2.1%) 0.23 (0.03-2.11)

Trazzera42 † 16 (13.0%) 24 (24.2%) 0.47 (0.23-0.94) 4 (3.3%) 5 (5.1%) 0.63 (0.17-2.42)

George43 10 (22.7%) 25 (71.4%) 0.12 (0.04-0.33) 1 (2.3%) 3 (8.6%) 0.25 (0.02-2.50)

* CI indicates confidence interval.

† Additional information provided by author (personal communications, 1/98-3/98)
175

Subchapter 16.3. Use of Chlorhexidine Gluconate at the Central Venous Catheter

Insertion Site

Practice Description

Microbial populations on the skin are routinely suppressed with antiseptic agents prior to

catheter insertion. Using an antiseptic solution for skin disinfection at the catheter insertion site

helps to prevent catheter-related infections. The physician uses an agent that has antimicrobial

properties to thoroughly cleanse the skin just prior to insertion of a central venous catheter. In

the United States, povidone-iodine (PI) is overwhelmingly the most commonly used agent for

this purpose. Recently, several studies have compared the efficacy of PI and chlorhexidine

gluconate (CHG) solutions in reducing vascular catheter-related infections.

Opportunities for Impact

If PI is the most commonly used agent for site disinfection in the United States even

though CHG may be superior, substantial opportunity exists for impact by switching to CHG.

Study Designs

The study characteristics of 6 randomized trials48-53 comparing any type of CHG solution

with PI solution for vascular catheter site care are shown in Table 16.3.1. The mean duration of

catheterization for the CHG and PI groups was comparable in most of the studies. There was no

significant difference in the sites at which catheters were inserted between the CHG and PI

groups. Several formulations of CHG were used, including9,12-14 an alcoholic solution and an

aqueous solution. All studies used 10% PI solution for the control arm.

Study Outcomes

All studies48-53 evaluated catheter colonization (Level 2 outcome) and all but one52

evaluated CR-BSI (Level 1 outcome). All studies evaluating CR-BSI as an outcome required the

recovery of the same microbial species from both the catheter segment and a blood culture.

Evidence for Effectiveness of the Practice

Most clinical trials have revealed that the use of CHG solution results in a significant

decrease in catheter colonization, but the evidence is not clear for CR-BSI (Table 16.3.2). Most

of the individual trials showed a trend in reducing CR-BSI incidence in patients using CHG

solution. The lack of significant results may be a result of insufficient statistical power in the

individual studies. A formal meta-analysis of the published trials would be valuable in assessing

the comparative efficacy of PI versus CHG for central venous catheter site disinfection. Using

explicit inclusion criteria and accepted quantitative methods, a meta-analysis54-56 can often help

clarify the features of individual studies that have divergent results57 and increase statistical

power since several small studies can be pooled.58

Potential for Harm

Only one study reported adverse effects from the use of either antiseptic solution. Maki et

al48 found erythema at the insertion site in 28.3% of catheters in the PI group and in 45.3% of

catheters in the CHG group (p=0.0002). However, there was no statistically significant

difference in erythema among these 2 groups and those patients whose site was disinfected with

alcohol. Hypersensitivity reactions to chlorhexidine-silver sulfadiazine impregnated central
176

venous catheters and to use of CHG for bathing have been reported. Hypersenstivity reactions

were not reported in any of the studies, but clinicians should be aware of such potential side

effects. Another concern is the development of bacterial resistance. However, there have been

few reports of bacterial resistance to CHG despite its widespread use for several decades.

Costs and Implementation

The cost of CHG is approximately twice that of PI with an absolute difference of $0.51

(approximately $0.92 versus $0.41 for a quantity sufficient to prepare a central venous catheter

insertion site). If meta-analysis suggests that CHG use is effective in reducing the risk of CRBSI, a formal economic evaluation of this issue is required.

Comment

The use of chlorhexidine gluconate rather than povidone-iodine solution for catheter site

care may be an effective and simple measure for improving patient safety by reducing vascular

catheter-related infections. Formal meta-analysis and economic evaluations are required before

strongly recommending that CHG replace PI for central venous catheter site disinfection in

appropriate patient populations.
177

Table 16.3.1. Characteristics of studies comparing chlorhexidine gluconate (CHG) and

povidone-iodine (PI) solutions for vascular catheter site care*

Study Description† Number of

Catheters

(Treatment,

Control)

Mean

Catheter

Duration in

Days

(Treatment,

Control)

Catheter

Colonization‡

CatheterRelated

Bloodstream

Infection‡

Maki48: 441 ICU

patients (2% aqueous

CHG solution in 214, PI

in 227)

214, 227 5.3, 5.3 SQ (>15 CFU) CX, NoSource,

Sx

Sheehan49: 189 ICU

patients (2% aqueous

CHG solution in 94, PI

in 95)

169,177 NA SQ (>15 CFU) CX, NoSource,

Sx

Meffre50: 1117 hospital

patients (CHG solution

of 0.5% alcohol 70% in

568, PI in 549)

568, 549 1.6, 1.6 SQ (>15 CFU) or

QN (>103

CFU/mL)

[Local or Sx] or

[CX, NoSource]

Mimoz51: ICU patients

(Biseptine§ vs. PI)

170, 145 4.5, 3.9 QN (>103

XFU/mL)

CX, Sx

Cobett and LeBlanc52:

244 hospital patients

(0.5% alcohol 70% in 8,

PI in 161)

83, 161 1.6, 1.7 SQ (>15 CFU)¶ NA

Humar et al53: 3374 ICU

patients (0.5% alcohol

in 193 and 181/193

193, 181 5.3, 6. SQ (>15 CFU) CX, Molec,

NoSource

* CFU indicates colony forming units; CX, same organism or species matched between blood

and catheter segment culture; ICU: intensive care units; Local: local signs of infection; Molec:

same organism confirmed by molecular subtyping; NA:not available; NoSource: no other

source of infection; QN: quantitative; Sx: clinical symptoms of bloodstream infection; SQ:

semiquantitative.

† All studies used 10% povidone-iodine solution.

‡ Catheter segments (or site) cultured and criteria for a positive culture are given in parenthesis.

§ Biseptine consists of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, 4%

benzyl alcohol.

¶ Required one of the following symptoms: fever, erythema, heat at the site, and pain.
178

Table 16.3.2. Results of Studies Comparing Chlorhexidine Gluconate (CHG) and Povidoneiodine (PI) Solutions for Vascular Catheter Site Care *

Catheter Colonization

(Positive Cultures)

Catheter Related

Bloodstream Infection

CHG

Solution

PI Solution

RR (95% CI)

CHG vs. PI

CHG

Solution

PI Solution

RR (95% CI)

CHG vs. PI

Maki48 5/214 21/227 0.25 (0.10,0.66) 1/214 6/227 0.18 (0.02,1.46)

Sheehan9 3/169 12/177 0.22 (0.06,0.75) 1/169 1/177 1.05 (0.07,16.61)

Meffre50 9/568 22/549 0.40 (0.18,0.85) 3/568 3/549 0.97 (0.20,4.77)

Mimoz51 12/170 24/145 0.43 (0.22,0.82) 3/170 4/145 0.64 (0.15,2.81)

Cobett and

LeBlanc52†

6/83 23/161 0.49 (0.31,0.77) - - -

Humar53 36/116 27/116 1.33 (0.87,2.04) 4/193 5/181 0.75 (0.20,2.75)

* CI indicates confidence interval; RR, relative risk.

† Additional information was provided by authors

Subchapter 16.4. Other Practices

Practices That Appear Promising

Use of heparin with central venous catheters. Because an association has been shown between

thrombus formation and catheter-related infection, clinicians usually use heparin, in a variety of

forms: 1) as flushes to fill the catheter lumens between use; 2) injected subcutaneously; or 3)

bonded on the catheter. A meta-analysis of 12 randomized trials evaluating prophylactic use of

heparin in patients using central venous catheters has shown that prophylactic heparin decreases

catheter-related venous thrombosis (Level 2 outcome; RR 0.43, 95% CI: 0.23-078) and bacterial

colonization (Level 2 outcome; RR 0.18, 95% CI: 0.06-0.60) and may decrease CR-BSI (Level 1

outcome; RR 0.26, 95% CI: 0.07-1.03).59 Since subcutaneous heparin also offers benefit in

reducing venous thromboembolism in certain patient populations (see Chapter 31), this is likely

to be a reasonable strategy even though CR-BSIs have not definitely been shown to be reduced.

However use of heparin is associated with several side effects, such as heparin-induced

thrombocytopenia and bleeding.

Tunneling short-term central venous catheters. Since the primary site of entry for

microorganisms on the central venous catheter is the site of cutaneous insertion,60 tunneling the

catheter through the subcutaneous tissue may decease the incidence of infection. Several trials

have evaluated the effect of tunneling on catheter-related infection. A recent meta-analysis has

summarized the potential benefit.61 The meta-analysis included 7 trials and found that compared

with patients receiving standard catheter placement, tunneling decreased bacterial colonization

(Level 2 outcome; RR 0.61, 95% CI: 0.39-0.95) and decreased CR-BSI (Level 1 outcome; RR

0.56, 95% CI: 0.31-1).61 However, the benefit of tunneling came primarily from one trial using

the internal jugular as the site of catheter placement; the reduction in CR-BSI no longer reached

statistical significance when data from the several subclavian catheter trials were pooled (RR

0.71; 95% CI 0.36-1.43).61 The authors concluded appropriately that current evidence does not
179

support the routine use of tunneling central venous catheters. This could change if the efficacy of

tunneling is clearly demonstrated at different placement sites and relative to other interventions

(eg, antiseptic coated catheters).61

Ineffective Practices

Intravenous antimicrobial prophylaxis. There is no evidence to support the systemic use of

either vancomycin62 or teicoplanin63 during insertion of central venous catheters. The

randomized studies evaluating the use on intravenous vanomycin or teicoplanin have failed to

demonstrate that this intervention reduces CR-BSI (Level 1 outcome).62, 63 Given the theoretical

risk of developing resistance to the antimicrobial agents used for prophylaxis, this practice is not

recommended.

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30. Sherertz RJ, Ely EW, Westbrook DM, et al. Education of physicians-in-training can

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31. Tennenberg S, Lieser M, McCurdy B, et al. A prospective randomized trial of an antibioticand antiseptic-coated central venous catheter in the prevention of catheter-related

infections. Arch Surg 1997;132:1348-1351.
181

32. Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related

bloodstream infection by use of an antiseptic-impregnated catheter. A randomized,

controlled trial. Ann Intern Med 1997;127:257-266.

33. van Heerden PV, Webb SA, Fong S, Golledge CL, Roberts BL, Thompson WR. Central

venous catheters revisited–infection rates and an assessment of the new Fibrin Analysing

System brush. Anaesth Intensive Care 1996;24:330-333.

34. Hannan M, Juste R, Shankar U, Nightingale C, Azadian B, Soni N. Colonization of triple

lumen catheters. A study on antiseptic-bonded and standard catheters [abstract]. Clin

Intensive Care 1996;7:56.

35. Bach A, Bohrer H, Bottiger BW, Motsch J, Martin E. Reduction of bacterial colonization

of triple-lumen catheters with antiseptic bonding in septic patients [abstract].

Anesthesiology 1994;81:A261.

36. Bach A, Schmidt H, Bottiger B, et al. Retention of antibacterial activity and bacterial

colonization of antiseptic-bonded central venous catheters. J Antimicrob Chemother

1996;37:315-322.

37. Heard SO, Wagle M, Vijayakumar E, et al. Influence of triple-lumen central venous

catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheterrelated bacteremia. Arch Intern Med 1998;158:81-87.

38. Collin GR. Decreasing catheter colonization through the use of an antiseptic-impregnated

catheter: a continuous quality improvement project. Chest 1999;115:1632-1640.

39. Ciresi DL, Albrecht RM, Volkers PA, Scholten DJ. Failure of antiseptic bonding to prevent

central venous catheter-related infection and sepsis. Am Surg 1996;62:641-646.

40. Pemberton LB, Ross V, Cuddy P, Kremer H, Fessler T, McGurk E. No difference in

catheter sepsis between standard and antiseptic central venous catheters. A prospective

randomized trial. Arch Surg 1996;131:986-989.

41. Ramsay J, Nolte F, Schwarmann S. Incidence of catheter colonization and catheter-related

infection with an antiseptic-impregnated triple lumen catheter [abstract]. Crit Care Med

1994;22:A115.

42. Trazzera S, Stern G, Rakesh B, Sinha S, Reiser P. Examination of antimicrobial-coated

central venous catheters in patients at high risk for catheter-related infections in a medical

intensive care unit and leukemia/bone marrow transplant unit [abstract]. Crit Care Med

1995;23:A152.

43. George SJ, Vuddamalay P, Boscoe MJ. Antiseptic-impregnated central venous catheters

reduce the incidence of bacterial colonization and associated infection in

immunocompromised transplant patients. Eur J Anaesthesiol 1997;14:428-431.

44. Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD. Efficacy of antiseptic-impregnated

central venous catheters in preventing catheter-related bloodstream infection: a metaanalysis. JAMA 1999;281:261-267.

45. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and

rifampin for the prevention of catheter-related colonization and bloodstream infections. A

randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann

Intern Med 1997;127:267-274.

46. Darouiche RO, Raad, II, Heard SO, et al. A comparison of two antimicrobial-impregnated

central venous catheters. Catheter Study Group. N Engl J Med 1999;340:1-8.

47. Veenstra DL, Saint S, Sullivan SD. Cost-effectiveness of antiseptic-impregnated central

venous catheters for the prevention of catheter-related bloodstream infection. JAMA

1999;282:554-560.
182

48. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine,

alcohol, and chlorhexidine for prevention of infection associated with central venous and

arterial catheters. Lancet 1991;338:339-343.

49. Sheehan G, Leicht K, O'Brien M, Taylor G, Rennie R. Chlorhexidine versus povidineiodine as cutaneous antisepsis for prevention of vascular-catheter infection [abstract].

Program and abstracts of the Interscience Conference on Antimicrobial Agents and

Chemotherapy 1993;33:A1616.

50. Meffre C, Girard R, Hajjar J, Fabry J. Is peripheral venous catheter colonisation related to

antiseptic used for disinfection of the insertion site? Hygiene 1995;9:45.

51. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic

solutions for prevention of central venous or arterial catheter colonization and infection in

intensive care unit patients. Crit Care Med 1996;24:1818-1823.

52. Cobett S, LeBlanc A. IV site infection: a prospective, randomized clinical trial comparing

the efficacy of three methods of skin antisepsis: CINA conference '99. CINA: Official

Journal of the Canadian Intravenous Nurses Association 1999;15:48-49.

53. Humar A, Ostromecki A, Direnfeld J, et al. Prospective randomized trial of 10% povidoneiodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of

central venous catheter infection. Clin Infect Dis 2000;31:1001-1007.

54. Yusuf S. Obtaining medically meaningful answers from an overview of randomized

clinical trials. Stat Med 1987;6:281-294.

55. Light RJ. Accumulating evidence from independent studies: what we can win and what we

can lose. Stat Med 1987;6:221-231.

56. Hennekens CH, Buring JE, Hebert PR. Implications of overviews of randomized trials. Stat

Med 1987;6:397-409.

57. Sacks HS, Berrier J, Reitman D, Ancona Berk VA, Chalmers TC. Meta-analyses of

randomized controlled trials. N Engl J Med 1987;316:450-455.

58. Gelber RD, Goldhirsch A. Interpretation of results from subset analyses within overviews

of randomized clinical trials. Stat Med 1987;6:371-388.

59. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous

and pulmonary artery catheters: a meta-analysis of randomized controlled trials. Chest

1998;113:165-171.

60. Mermel LA, McCormick RD, Springman SR, Maki DG. The pathogenesis and

epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a

prospective study utilizing molecular subtyping. Am J Med 1991;91:197S-205S.

61. Randolph AG, Cook DJ, Gonzales CA, Brun-Buisson C. Tunneling short-term central

venous catheters to prevent catheter-related infection: a meta-analysis of randomized,

controlled trials. Crit Care Med 1998;26:1452-1457.

62. McKee R, Dunsmuir R, Whitby M, Garden OJ. Does antibiotic prophylaxis at the time of

catheter insertion reduce the incidence of catheter-related sepsis in intravenous nutrition? J

Hosp Infect 1985;6:419-425.

63. Ljungman P, Hagglund H, Bjorkstrand B, Lonnqvist B, Ringden O. Peroperative

teicoplanin for prevention of gram-positive infections in neutropenic patients with

indwelling central venous catheters: a randomized, controlled study. Support Care Cancer

1997;5:485-488.
183

Final Comment to Chapter 16

Infections due to central venous catheters are common and lead to substantial morbidity

and health care costs. Several practices will likely reduce the incidence of this common patient

safety problem, including the use of maximum sterile barrier precautions during catheter

insertion, use of catheters coated with antibacterial or antiseptic agents, and use of chlorhexidine

gluconate at the insertion site. Additionally, use of heparin and tunneling of the central venous

catheter may prove to be effective in reducing CR-BSI. However, the relative efficacy of these

interventions is unclear. Also, a clear and formal delineation of the economic consequences of

combining several of these patient safety practices is necessary.
184
185

Chapter 17. Prevention of Ventilator-Associated Pneumonia

Harold R Collard, MD

University of Colorado Health Sciences Center

Sanjay Saint, MD, MPH

University of Michigan School of Medicine

Introduction

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in

the intensive care unit (ICU).1

 The incidence of VAP varies greatly, ranging from 6 to 52% of

intubated patients depending on patient risk factors. The cumulative incidence is approximately

1-3% per day of intubation. Overall, VAP is associated with an attributable mortality of up to

30%. Attributable mortality approaches 50% when VAP is caused by the more virulent

organisms that typify late-onset VAP (occurring 4 or more days into mechanical ventilation).

The cost per episode of VAP is substantial, although specific data are lacking. The average cost

per episode of nosocomial pneumonia is estimated at $3000 to $6000, and the additional length

of stay for patients who develop VAP is estimated at 13 days.1,2

VAP is typically categorized as either early-onset VAP (occurring in the first 3-4 days of

mechanical ventilation) or late-onset VAP. This distinction is important microbiologically.

Early-onset VAP is commonly caused by antibiotic-sensitive community-acquired organisms

(eg, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus). Lateonset VAP is commonly caused by antibiotic-resistant nosocomial organisms (eg, Pseudomonas

aeruginosa, methicillin-resistant Staphylococcus aureus, Acinetobacter species, and

Enterobacter species). Most episodes of ventilator-associated pneumonia (VAP) are thought to

develop from the aspiration of oropharyngeal secretions containing potentially pathogenic

organisms. Aspiration of gastric secretions may also contribute, though likely to a lesser degree.

Tracheal intubation interrupts the body’s anatomic and physiologic defenses against aspiration,

making mechanical ventilation a major risk factor for VAP.

This chapter reviews 4 practices that carry the potential to reduce the incidence of VAP

in patients receiving mechanical ventilation. They are: variation in patient positioning,

continuous aspiration of subglottic secretions, selective digestive tract decontamination, and the

use of sucralfate.

Subchapter 17.1. Patient Positioning: Semi-recumbent Positioning and Continuous

Oscillation

Background

Aspiration of gastric secretions likely contributes to the development of VAP.1

 Semirecumbent positioning of mechanically ventilated patients may help reduce the incidence of

gastroesophogeal reflux and lead to a decreased incidence of VAP. Immobility in critically ill

patients leads to atelectasis and decreased clearance of bronchopulmonary secretions. Both of

these sequelae may lead to increased risk of VAP. Continuous rotation and movement of

critically ill patients (termed continuous oscillation) may thus help prevent such changes.
186

Semi-recumbent positioning

Practice Description

Semi-recumbent positioning is generally defined as elevation of the head of the bed to 45

degrees. This is generally achieved in a hospital bed with patients’ feet remaining parallel to the

floor (ie, the entire bed is not tilted) but this is not explicitly described in the published trials.

Semi-recumbency is generally continued for the duration of mechanical ventilation.

Opportunities for Impact

Outside of select medical centers that have studied this practice, semi-recumbent

positioning has not been widely adopted as the standard of care. Thus, such an intervention

would have enormous opportunity for impact should it prove beneficial.

Study Designs

There have been three trials of semi-recumbent patient positioning and its effect on the

incidence of VAP.3-5 Two of these studies measured aspiration events using nuclear medicine

techniques, the other was a randomized trial with the primary outcome being VAP. In the one

randomized trial, 86 patients were randomized at the time of intubation to semi-recumbent body

position (45 degrees) or supine body position (0 degrees).3

 All patients received the same general

critical care (eg, sterile endotracheal suctioning, stress ulcer prophylaxis with sucralfate if

tolerating oral medications, no ventilator tubing changes, no selective digestive tract

decontamination).

Study Outcomes

In the one randomized clinical trial, VAP was clinically defined as a new and persistent

infiltrate on chest radiography, plus two of the following: temperature of >38.3C, leukocyte

count >12,000/mm3

 or <4000/mm3, purulent tracheal secretions.3 Microbiologic confirmation

required the above criteria be met and the isolation of pathogenic bacteria from an endotracheal

aspirate or bronchoscopic procedure. Mortality was reported at time of discharge from the ICU.

Both studies of the frequency of aspiration measured radioisotope counts (counts per minute) of

endotracheal aspirates at various time points before during and after semi-recumbent

positioning.4,5

Evidence for Effectiveness of the Practice

Only one randomized clinical trial of semi-recumbent patient positioning in mechanically

ventilated patients has been published to date (see Table17.1.1). Semi-recumbent positioning

was associated with a statistically significant reduction in both clinically and microbiologicallydiagnosed VAP.3

 There was no significant difference in mortality. These findings corroborate

earlier studies that demonstrated decreased frequency of gastroesophogeal reflux with semirecumbent positioning,4,5 and an independent association of supine positioning with the

development of VAP.6
187

Potential for Harm

No adverse effects were observed in patients randomized to semi-recumbent positioning.3

However, patients were excluded if they had any of the following conditions: recent abdominal

or neurologic surgery (<7 days), shock refractory to vasoactive therapy, and previous recent

endotracheal intubation (<30 days).

Costs and Implementation

The cost of semi-recumbent positioning is negligible and implementation is simple but

will require health care provider education.

Continuous oscillation

Practice Description

Continuous oscillation utilizes mechanical beds that employ either rotating platforms or

alternating inflation/deflation of mattress compartments to turn patients from side to side. These

beds achieve 40 to 60 degrees of tilt and can cycle every 5-30 minutes as programmed. In

general, in published trials, continuous oscillation was started within 24 hours of admission to

the ICU and continued until discharge.

Opportunities for Impact

Continuous oscillation is infrequently applied to critically ill patients. Thus, this

intervention would have significant opportunity for impact should it prove beneficial.

Study Designs

A meta-analysis of six randomized controlled trials evaluated the effect of continuous

oscillation on clinical outcomes, including pneumonia, in critically ill patients.7

 The vast

majority of patients were mechanically ventilated but the absolute percentage is not reported in

most trials. Five of the six trials included were limited to surgical and/or neurologic patients. A

subsequent randomized controlled trial included 103 medical and surgical patients.8

 In most

cases, continuous oscillation was compared to standard critical care practice of rolling patients

every two hours.

Study Outcomes

The definition of VAP varied among trials but was generally clinical and required a new

infiltrate on chest radiography, fever, and leukocytosis. Microbiologic confirmation was not

consistently obtained. Mortality was recorded at time of ICU discharge.

Evidence for Effectiveness of the Practice

The role of continuous oscillation in the prevention of VAP is unclear (see Table 17.1.1).

A meta-analysis of six randomized controlled trials on this subject found a statistically

significant reduction in the risk of pneumonia.7

 Five of these studies were limited to surgical

and/or neurologic patients. The sixth study, which included primarily medical patients, failed to

find any significant effect.9

 A subsequent randomized controlled trial of medical and surgical

patients also failed to find any benefit.8
188

Potential for Harm

There were no significant risks of continuous oscillation in any of the randomized trials.

Inadvertent disconnection of intravenous lines, increased ventricular ectopy, and patient

intolerance were reported, but not quantified. Conscious patients tolerated the procedure poorly.

Costs and Implementation

The incremental cost of specialized beds capable of continuous oscillation has been

estimated at approximately $100 per day.9

 A significant reduction in VAP incidence and length

of stay could result in cost savings.

Comment

Both semi-recumbent positioning and continuous oscillation are relatively low-cost, lowrisk interventions. The one randomized trial to date of semi-recumbent positioning shows it to be

an effective method of reducing VAP. While it has not proven to provide a mortality benefit,

semi-recumbent positioning is a safe and straightforward intervention whose effectiveness

should be confirmed by additional randomized clinical trials. Continuous oscillation is less

clearly beneficial, although it may be effective in certain subgroups of patients (eg, surgical,

neurologic). It also deserves continued study.
189

Table 17.1.1. Patient positioning*

Study Design Study

Design,

Outcomes

Pneumonia

or

Aspiration

Mortality

Semi-recumbent positioning

Randomized controlled trial of semi-recumbent

patient positioning in 86 mechanically ventilated

patients. Primary outcome was VAP. (Drakulovic,

1999)3

Level 1,

Level 1

RR 0.24

(p=0.003)

RR 0.64

(p=0.289)

Two-period crossover trial of semi-recumbent

patient positioning in 15 mechanically ventilated

patients. Primary outcome was pulmonary

aspiration. (Orozco-Levi, 1995)4

Level 3,

Level 2

RR 0.65

(p<0.01)

–

Randomized two-period crossover trial of semirecumbent patient positioning in 15 mechanically

ventilated patients. Primary outcome was

pulmonary aspiration. (Torres, 1992)5

Level 3,

Level 2

RR 0.23

(p=0.036)

–

Continuous oscillation

Randomized controlled trial of continuous

oscillation in 103 critically ill medical and surgical

patients (90% mechanically ventilated). Primary

outcomes included pneumonia. (Traver, 1995)8

Level 1,

Level 1

RR 0.62

(p=0.21)

RR 0.85

(p>0.05)

Meta-analysis of 6 randomized controlled trials of

continuous oscillation in critically ill surgical or

stroke patients (majority mechanically ventilated).

(Choi, 1992)7

Level 1A,

Level 1

RR 0.50

(p=0.002)

No significant

difference

(data not

reported)

Randomized controlled trial of continuous

oscillation in 86 critically ill medical patients

(majority mechanically ventilated). Primary

outcomes included pneumonia. (Summer, 1989)9

Level 1,

Level 1

RR 0.57

(p=0.40)

RR 0.93

(p>0.05)

* RR indicates relative risk; VAP, ventilator-associated pneumonia.
190

References

1. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients:

epidemiology and prevention in 1996. Semin Respir Infect. 1996;11:32-53.

2. Thompson R. Prevention of nosocomial pneumonia. Med Clin North Am. 1994;78:1185-

1198.

3. Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M. Supine body

position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a

randomised trial. Lancet. 1999;354:1851-1858.

4. Orozco-Levi M, Torres A, Ferrer M, Piera C, el-Ebiary M, de la Bellacasa JP, et al.

Semirecumbent position protects from pulmonary aspiration but not completely from

gastroesophageal reflux in mechanically ventilated patients. Am J Respir Crit Care Med.

1995;152:1387-1390.

5. Torres A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A, et al. Pulmonary

aspiration of gastric contents in patients receiving mechanical ventilation: the effect of

body position. Ann Intern Med. 1992;116:540-543.

6. Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA.

1993;270:1965-1970.

7. Choi SC, Nelson LD. Kinetic Therapy in Critically Ill Patients: Combined Results Based

on Meta-Analysis. J Crit Care. 1992;7:57-62.

8. Traver GA, Tyler ML, Hudson LD, Sherrill DL, Quan SF. Continuous oscillation: outcome

in critically ill patients. J Crit Care. 1995;10:97-103.

9. Summer WR, Curry P, Haponik EF, Nelson S, Elston R. Continuous Mechanical Turning

of Intensive Care Unit Patients Shortens Length of Stay in Some Diagnostic-Related

Groups. J Crit Care. 1989;4:45-53.

Subchapter 17.2. Continuous Aspiration of Subglottic Secretions

Background

Ventilator-associated pneumonia (VAP) frequently develops from the aspiration of

oropharyngeal secretions containing potentially pathogenic organisms.1

 Tracheal intubation

interrupts the body’s anatomic and physiologic defenses against aspiration, making mechanical

ventilation a major risk factor for VAP. The accumulation of contaminated oropharyngeal

secretions above the endotracheal tube cuff may contribute to the risk of aspiration.1

 Removal of

these pooled secretions through suctioning of the subglottic region, termed continuous aspiration

of subglottic secretions (CASS), may reduce the risk of developing VAP.

Practice Description

Continuous aspiration of subglottic secretions requires intubation with specially designed

endotracheal tubes (see Figure 17.2.1). These endotracheal tubes contain a separate dorsal lumen

that opens into the subglottic region, allowing for aspiration of any pooled secretions. The

amount of secretions is monitored (usually daily) and the patency of the suction lumen is tested

frequently (every few hours). In studies of the impact of this practice, aspiration has been applied

from time of intubation to time of extubation. One of the studies tested manual aspiration

performed hourly instead of continuous mechanical aspiration.2
191

Opportunities for Impact

Continuous aspiration of subglottic secretions is an uncommon practice. The

opportunities for impact are therefore significant should this practice prove beneficial in

lowering rates of VAP.

Study Designs

There have been three randomized controlled trials of CASS to date.2-4 (Table 17.2.1)

Two have included both medical and surgical patients requiring mechanical ventilation for

greater than 72 hours and one included only post-cardiac surgery patients. All three studies

randomized patients to CASS or standard care. Attempts were made to control for additional,

potentially effective preventive strategies such as patient positioning, frequency of ventilator

circuit changes, type of stress ulcer prophylaxis used, and administration of antibiotics.

Study Outcomes

All trials reported development of VAP and mortality at the time of extubation, ICU or

hospital discharge. VAP was generally defined as a new radiographic infiltrate plus two of the

following: fever, leukocytosis/leukopenia, or purulent tracheal aspirate. Microbiologic

confirmation was not consistently obtained. Time to development of VAP was also reported.

Mortality was reported at time of discharge from the hospital.

Evidence for Effectiveness of the Practice

One of the three trials found a statistically significant decrease in the incidence of VAP

with CASS when compared to standard treatment, while a second study showed a strong trend

(See Table 17.2.1).2,3 All three trials reported a statistically significant delay in the time to

development of VAP, ranging from 48 hours to 8 days. Two trials found a decreased incidence

of VAP caused by Staphylococcus aureus and Hemophilus influenzae, but no change was

observed in the incidence of VAP caused by Pseudomonas aeruginosa or Enterobacteriaceae.

3,4

No difference in mortality was observed in any of the trials.

Potential for Harm

There is minimal potential for harm to patients from the application of CASS and no

adverse patient events were reported in over 150 patients.4

Costs and Implementation

The cost and cost-effectiveness of CASS have not been examined. The direct costs

appear minimal. Hi-Lo Evac tubes cost approximately 25% more than standard endotracheal

tubes, putting the estimated cost of each unit at less than $1.2 The cost-savings per episode of

VAP prevented could therefore be substantial. Implementation would largely be a matter of

making the specialized endotracheal tubes available and providing staff training. The mechanical

suctioning apparatus would require frequent monitoring by nursing or respiratory therapy to

insure adequate function.

Comment

Continuous aspiration of subglottic secretions is a promising strategy for the prevention

of VAP. Two randomized controlled trials have suggested a decrease in the rate of VAP in

patients requiring prolonged (>3 days) mechanical ventilation (only one trial was statistically
192

significant). The third trial showed no difference, but the patient population in this trial included

many short-term intubations (mean duration of 36 hours) and was restricted to patients

undergoing cardiac surgery. Larger randomized controlled trials are needed to address the impact

of CASS more definitively.

Another interesting observation is the delay in the development of VAP and the

decreased incidence of Staphylococcus aureus and Hemophilus influenzae. This suggests that

CASS may provide most of its benefit by preventing early VAP caused by community-acquired

organisms, and its use could therefore be targeted to those patients requiring mechanical

ventilation for intermediate periods of time (ie, those at greatest risk for early VAP).

Figure 17.2.1. Diagram of continuous aspiration of subglottic secretions (copied with

permission)3
193

Table 17.2.1. Randomized trials of continuous aspiration of subglottic secretions*

Study Description Study

Outcomes

Relative Risk of

Pneumonia

(95% CI)

Relative Risk

of Mortality

(95% CI)

Kollef, 19994: 343 patients undergoing

cardiac surgery and requiring mechanical

ventilation

Level 1 0.61 (0.27-1.40) 0.86 (0.30-2.42)

Valles, 19953: 153 patients requiring

prolonged mechanical ventilation

Level 1 0.47 (0.21-1.06) 1.09 (0.72-1.63)

Mahul, 19922: 145 patients requiring

mechanical ventilation for more than 3 days

Level 1 0.46 (0.23-0.93) 1.14 (0.62-2.07)

* CI indicates confidence interval.

References

1. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients:

epidemiology and prevention in 1996. Semin Respir Infect. 1996;11:32-53.

2. Mahul P, Auboyer C, Jospe R, Ros A, Guerin C, el Khouri Z, et al. Prevention of

nosocomial pneumonia in intubated patients: respective role of mechanical subglottic

secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;18:20-25.

3. Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, et al. Continuous

aspiration of subglottic secretions in preventing ventilator- associated pneumonia. Ann

Intern Med. 1995;122:179-186.

4. Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continuous aspiration of

subglottic secretions in cardiac surgery patients. Chest. 1999;116:1339-1346.

Subchapter 17.3. Selective Digestive Tract Decontamination

Background

Selective digestive tract decontamination (SDD) involves the use of non-absorbable

antibiotics topically applied to the gastrointestinal tract in an effort to sterilize the oropharynx

and stomach. The goal is to decrease the pathogenicity of aspirated secretions and thereby reduce

the incidence of VAP.

Practice Description

Most studies have used a combination of topical polymixin, tobramycin or gentamicin,

and amphotericin applied to the oropharynx (by hand) and the stomach (by nasogastric tube).1

About half of the studies also included a short (3-4 day) course of systemic intravenous

antimicrobial therapy, most commonly ceftriaxone. In general, topical antibiotics were applied

several times daily from the time of intubation until extubation (or shortly thereafter).
194

Opportunities for Impact

SDD is not widely used in the United States.1

 The Centers for Disease Control and

Prevention and the American Thoracic Society's guidelines published in the 1990s do not

recommend its routine use.2,3 Given the frequency and morbidity of VAP, if the practice is

beneficial substantial opportunity for patient safety enhancement exists.

Study Designs

There have been over 30 randomized controlled trials and seven meta-analyses of SDD

(see Table 17.3.1).4-10 A representative meta-analysis identified 33 randomized trials of SDD

using a structured search of the literature that met the authors’ methodologic inclusion criteria:

measurement of clinical outcomes (including VAP and mortality), inclusion of unselected patient

populations, and mechanical ventilation in at least half of patients.1

 As with several of the other

meta-analyses, individual trials in this particular meta-analysis were grouped into those that used

topical antibiotics only and those that used topical and systemic antibiotics. This meta-analysis

was unique in that the investigators obtained individual patient data for the majority of patients

(4343 (76%) of the 5727 patients involved).1

Study Outcomes

All meta-analyses reported risk of VAP and mortality at hospital or ICU discharge.

Individual study outcomes also included number of days intubated, length of ICU stay, duration

of antibiotic therapy, time to onset of VAP, and cost. Several meta-analyses performed subgroup

analysis to assess the importance of statistical methods (eg, quality of randomization, blinding,

VAP definition) and clinical factors (eg, Acute Physiology and Chronic Health Evaluation

(APACHE) score).

Evidence for Effectiveness of the Practice

All seven meta-analyses report substantial reduction in the risk of VAP with the use of

SDD (see Table 17.3.1). Four of seven meta-analyses report a statistically significant reduction

in mortality.4-6,8 Four of seven meta-analyses separately analyzed trials using topical antibiotics

only and those using topical and systemic antibiotics.4,6,8,9 All four revealed a statistically

significant mortality benefit with combined topical and systemic prophylaxis and no mortality

benefit with topical prophylaxis alone.1,6,8,9 However, these four meta-analyses did reveal a

significant decrease in VAP incidence in those given topical antibiotics only compared to the

placebo group.4,6,8,9 Several of the meta-analyses included subgroup analyses to assess the

benefit of SDD in patients categorized by type of illness (surgical, medical) and severity of

illness (APACHE score), with conflicting results.4,6

Potential for Harm

There were no significant adverse events reported in most trials, although allergic

reactions to the antibiotic preparations have been uncommonly noted. The primary long-term

concern with the widespread use of SDD is the development of antibiotic resistance.11-13 The

data are unclear regarding the impact of SDD on the emergence of resistant organisms, and no

study has demonstrated an impact of increased bacterial resistance on morbidity or mortality.

Costs and Implementation

The cost of implementing SDD appears minimal in most trials, but there have been no in

depth reviews of the subject. Several trials have found that patients receiving SDD had lower
195

total antibiotic costs.14-16 Overall hospital costs also may be lower, mediated through the

decreased rate of VAP.17

Comment

SDD is a very promising method of reducing VAP and ICU-related mortality. The data

supporting a significant reduction in risk of VAP and short-term mortality with SDD using

topical and short-term intravenous antibiotics are strong. SDD is a relatively non-invasive

intervention and the additional financial cost is minimal. What remains to be determined is the

long-term effect of SDD on antibiotic resistance patterns, and the impact of such effect on

morbidity and mortality. Research into the impact of SDD on the emergence of antibiotic

resistance should be strongly encouraged.
196

Table 17.3.1. Meta-analyses of selective digestive tract decontamination*

Study Design Pneumonia (95% CI) Mortality (95% CI)

Nathens, 19996: 21 randomized

controlled trials of antibiotic

prophylaxis used to decrease

nosocomial respiratory tract infections;

dual analysis of medical and surgical

patients

Medical: OR 0.45 (0.33-

0.62)

Surgical: OR 0.19 (0.15-

0.26)

Medical

Overall: OR 0.91 (0.71-1.18)

Topical/IV: OR 0.75 (0.53-1.06)

Topical: OR 1.14 (0.77-1.68)

Surgical

Overall: OR 0.70 (0.52-0.93)

Topical/IV: OR 0.60 (0.41-0.88)

Topical: OR 0.86 (0.51-1.45)

D’Amico, 19981: 33 randomized

controlled trials from of antibiotic

prophylaxis used to decrease

nosocomial respiratory tract infections;

dual analysis of topical and systemic

antibiotics combined and topical

antibiotics alone

Overall: not reported

Topical/IV: OR 0.35

(0.29-0.41)

Topical: OR 0.56 (0.46-

0.68)

Overall: OR 0.88 (0.78-0.98)

Topical/IV: OR 0.80 (0.69-0.93)

Topical: OR 1.01 (0.84-1.22)

Hurley, 19955: 26 randomized

controlled trials of antibiotic

prophylaxis used to decrease

nosocomial respiratory tract infections

Overall: OR 0.35 (0.30-

0.42)

Overall: OR 0.86 (0.74-0.99)

Kollef, 19947: 16 randomized

controlled trials of antibiotic

prophylaxis used to decrease

nosocomial respiratory tract infections

Overall: RD 0.145

(0.116-0.174)

Overall: RD 0.019 (-0.016-0.054)

Heyland, 19948: 25 randomized

controlled trials of antibiotic

prophylaxis used to decrease

nosocomial respiratory tract infections;

performed subgroup analyses

Overall: RR 0.46 (0.39-

0.56)

Topical/IV: RR 0.48

(0.39-0.60)

Topical: RR 0.43 (0.32-

0.59)

Overall: RR 0.87 (0.79-0.97)

Topical/IV: RR 0.81 (0.71-0.95)

Topical: RR 1.00 (0.83-1.19)

SDD Trialists’ Collaborative Group,

19939

: 22 randomized controlled trials

of antibiotic prophylaxis used to

decrease nosocomial respiratory tract

infections; performed subgroup

analyses

Overall: OR 0.37 (0.31-

0.43)

Topical/IV: OR 0.33

(0.27-0.40)

Topical: OR 0.43 (0.33-

0.56)

Overall: OR 0.90 (0.79-1.04)

Topical/IV: OR 0.80 (0.67-0.97)

Topical: OR 1.07 (0.86-1.32)

Vandenbroucke-Grauls, 199110: 6

randomized controlled trials of

antibiotic prophylaxis used to decrease

nosocomial respiratory tract infections

Overall: OR 0.12 (0.08-

0.19)

Overall: OR 0.70 (0.45-1.09)

* CI indicates confidence interval; RD, risk difference, RR, relative risk; and OR, odds ratio.
197

References

1. D'Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of

antibiotic prophylaxis in critically ill adult patients: systematic review of randomised

controlled trials. BMJ. 1998;316:1275-1285.

2. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial

antimicrobial therapy, and preventive strategies. A consensus statement, American

Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996;153:1711-1725.

3. CDC. Guidelines for prevention of nosocomial pneumonia. Centers for Disease Control

and Prevention. MMWR Morb Mortal Wkly Rep. 1997;46:1-79.

4. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients:

epidemiology and prevention in 1996. Semin Respir Infect. 1996;11:32-53.

5. Hurley JC. Prophylaxis with enteral antibiotics in ventilated patients: selective

decontamination or selective cross-infection? Antimicrob Agents Chemother. 1995;39:941-

947.

6. Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical

patients: a systematic review of the evidence. Arch Surg. 1999;134:170-176.

7. Kollef MH. The role of selective digestive tract decontamination on mortality and

respiratory tract infections. A meta-analysis. Chest. 1994;105:1101-1108.

8. Heyland DK, Cook DJ, Jaeschke R, Griffith L, Lee HN, Guyatt GH. Selective

decontamination of the digestive tract. An overview. Chest. 1994;105:1221-1229.

9. Meta-analysis of randomised controlled trials of selective decontamination of the digestive

tract. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group.

BMJ. 1993;307:525-532.

10. Vandenbroucke-Grauls CM, Vandenbroucke JP. Effect of selective decontamination of the

digestive tract on respiratory tract infections and mortality in the intensive care unit.

Lancet. 1991;338:859-862.

11. van Saene HK, Stoutenbeek CP, Hart CA. Selective decontamination of the digestive tract

(SDD) in intensive care patients: a critical evaluation of the clinical, bacteriological and

epidemiological benefits. J Hosp Infect. 1991;18:261-277.

12. Ebner W, Kropec-Hubner A, Daschner FD. Bacterial resistance and overgrowth due to

selective decontamination of the digestive tract. Eur J Clin Microbiol Infect Dis.

2000;19:243-247.

13. Bartlett JG. Selective decontamination of the digestive tract and its effect on antimicrobial

resistance. Crit Care Med. 1995;23:613-615.

14. Quinio B, Albanese J, Bues-Charbit M, Viviand X, Martin C. Selective decontamination of

the digestive tract in multiple trauma patients. A prospective double-blind, randomized,

placebo-controlled study. Chest. 1996;109:765-772.

15. Verwaest C, Verhaegen J, Ferdinande P, Schetz M, Van den Berghe G, Verbist L, et al.

Randomized, controlled trial of selective digestive decontamination in 600 mechanically

ventilated patients in a multidisciplinary intensive care unit. Crit Care Med. 1997;25:63-

71.

16. Sanchez Garcia M, Cambronero Galache JA, Lopez Diaz J, Cerda Cerda E, Rubio Blasco

J, Gomez Aguinaga MA, et al. Effectiveness and cost of selective decontamination of the
198

digestive tract in critically ill intubated patients. A randomized, double-blind, placebocontrolled, multicenter trial. Am J Respir Crit Care Med. 1998;158:908-916.

17. Silvestri L, Mannucci F, van Saene HK. Selective decontamination of the digestive tract: a

life saver. J Hosp Infect. 2000;45:185-190.

Subchapter 17.4. Sucralfate and Prevention of VAP

Background

Aspiration of gastric secretions may contribute to the development of VAP. It has been

observed that gastric colonization by potentially pathogenic organisms increases with decreasing

gastric acidity, leading to the hypothesis that pH-altering drugs may cause increased rates of

VAP.1

 H2-antagonist therapy, widely used in mechanically-ventilated patients for stress ulcer

prophylaxis (see Chapter 34), significantly elevates gastric pH. Sucralfate, an alternative

prophylactic agent that does not affect gastric pH, may allow less gastric colonization with

potentially pathogenic organisms than H2-antagonists and therefore prevent some cases of VAP.

Practice Description

In general, 1 g of sucralfate suspension is given through a nasogastric tube every four to

six hours. When H2-antagonists are used, their dosing and frequency vary. A representative study

used 50 mg of ranitidine intravenously every eight hours, dose adjusted for creatinine clearance.2

Stress ulcer prophylaxis is usually started upon initiation of mechanical ventilation and

continued until extubation (Chapter 34).

Opportunities for Impact

Stress ulcer prophylaxis is usually given to critically ill ventilated patients. A large cohort

study of over 2000 critically ill patients suggests that the majority receive H2-antagonists

(71.8%) followed by sucralfate (7.0%) and combination therapy (15.4%) or other single agents

(omeprazole, antacids, prostaglandins).3

 There is, therefore, significant opportunity for impact

should sucralfate prove to lower rates of VAP and improve survival.

Study Designs

There have been over 20 randomized controlled trials of stress ulcer prophylaxis using

sucralfate, H2-antagonists, and other therapies in critically ill patients. Seven meta-analyses have

been published to date.2,4-10 The individual trials and meta-analyses have significant variation in

methodology. In general, the individual trials randomized critically ill patients to sucralfate, H2-

antagonists, other agents such as antacids and pirenzepine, or placebo. The majority of patients

included in these studies required mechanical ventilation. Various drug-drug, drug-placebo

combinations were compared, and the rates of VAP and mortality were recorded.

Study Outcomes

Most trials report development of VAP and mortality as primary endpoints. There is

significant variation in the definition of VAP used in these trials. In the largest and most recent

randomized trial, VAP was defined as a new radiographic infiltrate plus two of the following:

temperature of >38.5°C or <35.0°C, leukocyte count >10,000/mm3

 or <3000/mm3, purulent

sputum, and isolation of pathogenic bacterial from an endotracheal aspirate.8

 Mortality was

reported at time of discharge from the ICU.
199

Evidence for Effectiveness of the Practice

The results of the seven meta-analyses and one recent large randomized controlled trial

are inconclusive (see Table 17.4.1). The two largest meta-analyses to date suggest a decreased

incidence of VAP with sucralfate compared to H2-antagonists,4,6 and one reports a statistically

significant mortality benefit with sucralfate.6

 A recent randomized controlled trial of 1200

ventilated patients reports no significant difference between the two therapies in terms of VAP or

mortality.8

Potential for Harm

Sucralfate therapy has been associated with a statistically significant increased risk of

clinically important gastrointestinal bleeding when compared to H2-antagonists.8

 Clinically

important bleeding developed in 3.8% of patients receiving sucralfate compared with 1.7% of

patients receiving H2-antagonists (relative risk for H2-antagonist = 0.44, 95% CI: 0.21-0.92).8

Gastrointestinal bleeding in critically ill patients has an attributable mortality of approximately

12.5%.8

 While previous meta-analyses have suggested little difference in rates of gastrointestinal

bleeding between the various prophylactic agents,6

 these results from a large randomized trial are

convincing. There are very few adverse effects from sucralfate therapy aside from constipation,

rare nausea and vomiting and very rare bezoar formation and aluminum intoxication.11 Sucralfate

administration has been associated with transmission of vancomycin resistant enterococcus,

likely due to increased manipulation of patients’ nasogastric tubes.12 Unlike parenteral H2-

blockers, sucralfate mandates nasogastric tube placement in intubated patients. The drug can also

lead to decreased absorption of other medications.

Costs and Implementation

Several studies have looked at the cost-effectiveness of stress ulcer prophylaxis.13,14

Based on decision analysis, the cost per episode of gastrointestinal bleeding averted in high-risk

patients is several thousand dollars greater with H2-antagonists than with sucralfate.13 This cost

difference remains significant even if H2-antagonists are assumed to be 50% more effective.

There are no reliable data comparing overall costs from the actual clinical trials. The mean cost,

largely driven by prolonged length of stay, is significantly higher for patients who bleed than for

those who do not ($70,000 vs. $15-20,000), implying that in patients at high risk for GI bleeding

(eg, mechanically ventilated patients, those with a coagulopathy), stress ulcer prophylaxis may

be cost-neutral or even cost-saving (see also Chapter 34).14 Implementation of sucralfate use

would be largely an issue of staff education as administration is relatively uncomplicated.

Comment

The data supporting stress ulcer prophylaxis with sucralfate instead of H2-antagonists to

prevent VAP are inconclusive, and the theoretical contribution of increased gastric colonization

with potentially pathogenic organisms to the development of VAP is unproven. There are data

both supporting and refuting a decreased incidence of VAP with sucralfate. Most investigators

have found at least a trend toward decreased incidence of VAP with sucralfate, and larger studies

are warranted. The greatest benefit from sucralfate may be the prevention of late-onset VAP in

patients requiring long-term ventilation.15 Any increased risk of gastrointestinal bleeding with

sucralfate therapy in these patients may be offset by the decreased risk of VAP. Until the data are

more definitive, however, when stress ulcer prophylaxis is deemed appropriate (Chapter 34), the
200

use of H2-blockers seems preferable to sucralfate because of the former’s superiority in

preventing clinically important gastrointestinal bleeding.
201

Table 17.4.1. Studies of stress ulcer prophylaxis

Study Design Design,

Outcomes

Pneumonia*

(95% CI)

Mortality*

(95% CI)

Meta-analysis of randomized

controlled trials comparing

ranitidine with placebo,

sucralfate with placebo and

ranitidine with sucralfate for the

prevention of pneumonia in

critically ill patients. (Messori,

2000)

Level 1A,

Level 1

ranitidine vs.

sucralfate: 1.35

(1.07-1.70)

ranitidine vs.

placebo: 0.98

(0.56-1.72)

sucralfate vs.

placebo: 2.21

(0.86-5.65)

not reported

Multicenter randomized, blinded,

placebo-controlled trial of

sucralfate with ranitidine in 1200

critically ill mechanically

ventilated patients. Endpoints

were gastrointestinal bleeding,

VAP and mortality. (Cook,

1998)

Level 1,

Level 1

ranitidine vs.

sucralfate: 1.18

(0.92-1.51)

ranitidine vs.

sucralfate: 1.03

(0.84-1.26)

27 randomized trials of stress

ulcer prophylaxis in critically ill

patients. The majority of patients

were mechanically ventilated.

Endpoints were gastrointestinal

bleeding, pneumonia and

mortality. (Cook, 1996)

Level 1A,

Level 1

sucralfate vs. H2-

antagonist: 0.77

(0.60-1.01)

H2-antagonist vs.

placebo: 1.25

(0.78-2.00)

sucralfate vs. H2-

antagonist: 0.73

(0.54-0.97)

14 randomized trials of stress

ulcer prophylaxis in critically ill

patients. (Tryba, 1995)

Level 1A,

Level 1

sucralfate vs. H2-

antagonist/

antacid: 0.67

(p<0.05)

not reported

6 (outcome VAP) and 7

(outcome mortality) randomized

trials of stress ulcer prophylaxis

in critically ill patients. (Cook,

1995)

Level 1A,

Level 1

sucralfate vs. H2-

antagonist/

antacid: 0.50

(0.21-0.79)

sucralfate vs. H2-

antagonist: 0.71

(0.49-1.04)

sucralfate vs. antacid: 

 0.70 (0.52-0.94)

14 randomized trials of stress

ulcer prophylaxis in critically ill

patients. Endpoints were

gastrointestinal bleeding and

pneumonia. (Tryba. 1991)

Level 1A,

Level 1

sucralfate vs. H2-

antagonist: 0.50

(0.32-0.78)

sucralfate vs. antacid:

 0.40 (0.24-0.69)

sucralfate vs. H2-

antagonist/ antacid:

0.81 (NA)
202

Table 17.4.1. Studies of stress ulcer prophylaxis (cont.)

9 randomized trials of stress

ulcer prophylaxis in critically ill

patients. (Tryba, 1991)

Level

1A,

Level 1

sucralfate vs. H2-

antagonist/ antacid:

0.48 (p<0.05)

sucralfate vs. H2-

antagonist/ antacid:

0.72 (p<0.05)

8 randomized trials of stress

ulcer prophylaxis in critically ill

patients studying the rate of

pneumonia with different drug

regimens. (Cook, 1991)

Level

1A,

Level 1

sucralfate vs. H2-

antagonist/ antacid:

0.55 (0.28-1.06)

H2-antagonist/antacid

vs. placebo: 0.42

(0.17-1.11)

not reported

* Point estimates reflect odds ratio or relative risk.

References

1. Donowitz LG, Page MC, Mileur BL, Guenthner SH. Alteration of normal gastric flora in

critical care patients receiving antacid and cimetidine therapy. Infect Control. 1986; 7: 23-

26.

2. Tryba M. Prophylaxis of stress ulcer bleeding. A meta-analysis. J Clin Gastroenterol.

1991; 13: S44-55.

3. Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, et al. Risk factors for

gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N

Engl J Med. 1994; 330: 377-381.

4. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in

intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: metaanalysis of randomised controlled trials. BMJ. 2000; 321: 1103-1106.

5. Cook DJ, Laine LA, Guyatt GH, Raffin TA. Nosocomial pneumonia and the role of gastric

pH. A meta-analysis. Chest. 1991; 100: 7-13.

6. Cook DJ, Reeve BK, Guyatt GH, Heyland DK, Griffith LE, Buckingham L, et al. Stress

ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA.

1996; 275: 308-314.

7. Cook DJ. Stress ulcer prophylaxis: gastrointestinal bleeding and nosocomial pneumonia.

Best evidence synthesis. Scand J Gastroenterol Suppl. 1995; 210: 48-52.

8. Cook D, Guyatt G, Marshall J, Leasa D, Fuller H, Hall R, et al. A comparison of sucralfate

and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring

mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998; 338:

791-797.

9. Tryba M. Sucralfate versus antacids or H2-antagonists for stress ulcer prophylaxis: a metaanalysis on efficacy and pneumonia rate. Crit Care Med. 1991; 19: 942-949.

10. Tryba M, Cook DJ. Gastric alkalinization, pneumonia, and systemic infections: the

controversy. Scand J Gastroenterol Suppl. 1995; 210: 53-59.

11. McCarthy DM. Sucralfate. N Engl J Med. 1991; 325: 1017-1025.
203

12. Slaughter S, Hayden MK, Nathan C, Hu TC, Rice T, Van Voorhis J, et al. A comparison of

the effect of universal use of gloves and gowns with that of glove use alone on acquisition

of vancomycin-resistant enterococci in a medical intensive care unit. Ann Intern Med.

1996; 125: 448-456.

13. Ben-Menachem T, McCarthy BD, Fogel R, Schiffman RM, Patel RV, Zarowitz BJ, et al.

Prophylaxis for stress-related gastrointestinal hemorrhage: a cost effectiveness analysis.

Crit Care Med. 1996; 24: 338-345.

14. Erstad BL, Camamo JM, Miller MJ, Webber AM, Fortune J. Impacting cost and

appropriateness of stress ulcer prophylaxis at a university medical center. Crit Care Med.

1997; 25: 1678-1684.

15. Prod'hom G, Leuenberger P, Koerfer J, Blum A, Chiolero R, Schaller MD, et al.

Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or

sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med.

1994; 120: 653-662.

Final Comment to Chapter 17

Ventilator-associated pneumonia is common, costly, and morbid. This chapter confirms

that there are several low-risk interventions that carry the potential to reduce the frequency of

this complication. Further research will be needed to confirm the benefit of promising practices

(eg, semi-recumbency or continuous aspiration of subglottic secretions) or fully allay concerns

regarding practices that have potential for harm (eg, antibiotic resistance with selective

decontamination).
204

Section C. Surgery, Anesthesia, and Perioperative Medicine

Chapter 18. Localizing Care to High-Volume Centers

Chapter 19. Learning Curves for New Procedures – the Case of Laparoscopic

Cholecystectomy

Chapter 20. Prevention of Surgical Site Infections

Subchapter 20.1 Prophylactic Antibiotics

Subchapter 20.2. Perioperative Normothermia

Subchapter 20.3. Supplemental Perioperative Oxygen

Subchapter 20.4. Perioperative Glucose Control

Chapter 21. Ultrasound Guidance of Central Vein Catheterization

Chapter 22. The Retained Surgical Sponge

Chapter 23: Pre-Anesthesia Checklists To Improve Patient Safety

Chapter 24. The Impact Of Intraoperative Monitoring On Patient Safety

Chapter 25. Beta-blockers and Reduction of Perioperative Cardiac Events
205

Chapter 18. Localizing Care to High-Volume Centers

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Background

The extent to which experience in caring for illness—as represented by a higher volume

of cases—impacts outcomes has been well studied over the last 20 years. An extensive literature

covering a broad range of conditions and procedures documents superior outcomes for hospitals

and physicians with higher patient volumes.1-6 Drawing on such evidence, various investigators

have projected substantial reductions in mortality from regionalizing certain high-risk procedures

with established volume-outcome relationships.4-6

When volume-outcomes relationships reflect a “practice makes perfect” effect, it may be

reasonable to use volumes to assess quality of care. However, such relationships may also reflect

“selective referral,”

7-10 when anecdotal knowledge of the superior quality of high volume centers

exists in the community.11 In such cases, direct measurements of processes or outcomes may

represent more appropriate quality measures than volume alone.12,13

In an era of cost containment and a growing need for accountability for quality of care,

any connection between site or physician-specific experience and patient outcomes has far

reaching implications for patients, payers, and governmental agencies.14 In fact, the Leapfrog

Group (a consortium of major purchasers and purchasing coalitions) has made patient volume

one of their criteria for quality, and has recently begun a project examining evidence-based

referrals to high-volume centers (see also Chapter 55).15

The Institute of Medicine (IOM) recently sponsored a workshop to examine the evidence

supporting this relationship,16 part of which included a systematic review of investigations of the

volume-outcome association.17 This chapter summarizes the evidence supporting volumeoutcomes relationships, drawing heavily on the IOM’s systematic review and the workshop's

findings.

Practice Description

The use of information regarding volume and its proven or potential relationship with

better outcomes may result in several actions. Simply providing patients with volume data may

result in preferential selection of high-volume centers or providers. Patients might also be

incentivized to choose high-volume centers (eg, through reduced co-payments). Alternatively,

payers may elect to contract only with high-volume centers, or provide higher payments to these

sites. Finally, low-volume centers (eg, a hospital failing to meet a minimum threshold of bypass

operations) or providers (eg, a cardiologist failing to perform a minimum number of

angioplasties) might be restricted from continuing to perform the practice, through some

combination of credentialing, accreditation, or regulatory actions (see Chapter 56).

Opportunities for Impact

Assuming that a feasible method could be developed to localize care to high-volume

centers, a significant effect on patient safety and outcomes is likely. A recent study suggested

that more than 500 deaths could be avoided annually in California alone if care for disorders

with established volume-outcomes relationships were localized to more experienced centers.

Extrapolating nationally, such localization would save 4000 lives.6

 In the case of acute

myocardial infarction, transferring the care of these patients from hospitals in the lowest volume
206

quartile to those in the highest would save 2.3 lives per 100 patients.4

 The corresponding

“number needed to treat” (NNT) of 50 falls within the range of many accepted therapeutic

interventions.

Little information exists to assess differences in quality of care or rates of adverse events

in high or low-volume sites. For example, the extent to which increasing volume leads to fewer

medical errors or other direct impacts on patient safety (as opposed to specific improvement in

care processes for discrete procedures, which would fall outside our definition of patient safety

practices (Chapter 1)) is unknown. Ongoing prospective initiatives such as those proposed by the

Leapfrog Group15 may better quantify the various impacts of localizing care to high-volume

centers.

Study Designs

We analyzed one large systematic review of 88 studies examining the relationship

between volume and outcomes.17 Using a structured MEDLINE search, this review included

studies that examined health outcomes as the dependent variable with hospital and/or physician

volume as an independent variable. The IOM review included medical and surgical conditions

such as coronary artery bypass grafting, pediatric cardiac surgery, carotid endarterectomy,

abdominal aortic aneurysm repair, cancer surgery, coronary angioplasty, acute myocardial

infarction, AIDS, and multiple procedures. This chapter reviews the relationship for surgical

illnesses only.

The source studies of the IOM review were entirely observational in nature. Close

attention was paid to risk adjustment and statistical methods in assessment of results, and criteria

for inclusion in the review selected for population or community-based samples. Thus, the level

of the design is classified as Level 3A.

Study Outcomes

The IOM systematic review examined health outcomes as related to hospital or physician

volume. The primary outcome of interest was mortality. Other clinical outcomes were chosen

based on complications specific to the surgical procedure (eg, stroke following carotid

endarterectomy).

Evidence for Effectiveness of the Practice

Results of the systematic review are outlined in Table 18.1. The studies reviewed were of

variable design and analytic sophistication, with more recent investigations generally being of

higher quality. For all procedures, there was a consistent trend toward an association between

improved outcomes and higher hospital or physician-specific volume.* The evidence supporting

the volume-outcomes relationship was similar when looking at hospital volume (78% of studies

 

* This trend has one major exception, a study of volume-outcome relationships for 8 major

surgical procedures at Veterans Affairs hospitals across the country (Khuri SF, et al. Relation of

surgical volume to outcome in eight common operations: results from the VA National Surgical

Quality Improvement Program. Ann Surg. 1999;230:414-429). This comprehensive national

study found no significant volume-outcome relationship for any of the 8

procedures analyzed. While it is tempting to attribute these negative findings to unique aspects

of the VA system, this is also one of the few studies to employ robust risk-adjustment using

clinical and not administrative data. The authors of the IOM review take particular note of the

superior methodologic features and negative findings of this study.
207

showed an association) and physician volume (74% showed an association); the former was the

more frequently analyzed variable.

The impact of volume on outcomes varied across procedures and diagnoses. The effect

was most marked for complex cancer surgeries (ie, esophagectomy, pancreatoduodenectomy),

with numbers needed to treat (NNT) between 7 and 17. For commonly performed surgeries such

as coronary artery bypass grafting, the NNT was generally larger, but still within the range of

other accepted therapies. Carotid endarterectomy appeared to have a much higher NNT, but this

may be because the major adverse outcome of this surgery (ie, stroke) is often an indication for

surgery as well as a complication of it. This relationship cannot be discerned from administrative

data, and the studies upon which the NNT is based reported mortality, a less frequent

complication of carotid surgery than stroke, as a primary outcome. The few studies that collected

primary data (and would have been able to determine this important difference) were generally

small and of lower quality design, making their findings suspect.

The authors of the IOM systematic review conclude that the volume-outcomes

relationship exists, but they raise some caveats when interpreting the literature as a whole. They

first note that the literature describing the relationship in greatest detail come from a few singleState databases (63% of studies coming from New York State alone), possibly limiting the

generalizability of their results. Although few studies employed rigorous risk adjustment

methodologies using clinical data, the relationship between volume and outcomes was consistent

in these studies. Also, they raise a note of caution in interpreting this relationship because of the

possibility that publication bias (ie, studies that fail to demonstrate a volume-outcome

relationship might be less likely to be submitted or accepted for publication) has affected this

literature. Finally, they point out that the precise mechanism by which outcomes are improved

has yet to be elucidated; no study has reported the independent effects of ancillary personnel

expertise or hospital system factors on patient outcomes. For example, in interpreting the

improved outcomes of high volume centers in coronary artery bypass grafting, we do not

presently know what the relative contributions are of the surgeon, cardiac bypass team, cardiac

anesthesiologist, and hospital resources (eg, dedicated cardiothoracic intensive care units).

Potential for Harm

In the summary accompanying the IOM workshop's proceedings, several potential

pitfalls of localizing care to high volume settings were noted, as follows16:

• The focus on high volume providers may be a “distracting priority,” and

similar improvements in care may be achieved through more traditional local

quality improvement measures.

• Hospitals with high volumes may use that data to misrepresent their

experience in the absence of true outcomes data.

• High volume centers may achieve too much contractual leverage, leading to

price inflation.

• Counting procedures may lead to perverse incentives to perform procedures

that are not appropriate.

• Requiring high volumes will impede entry of new competitors into the

marketplace.

• Narrowing the choice of providers may negatively impact patient satisfaction

and override patients’ preferences for care (for example, if patients are forced

to travel long distances to receive care at a high volume center).
208

Several of these concerns have been borne out in published studies. In a study of

pediatric trauma centers, Tepas et al suggested that increases in volume may strain provider

resources and worsen patient outcomes.18 Even assuming potential improvements in patient

outcomes, diverting patients to large referral centers has important health policy implications14

and may decrease patient satisfaction.19

Costs and Implementation

The major barriers to implementing a selective referral program based on hospital

volume include the potential harms listed above, as well as several additional factors. These may

include patients' preference for care near home, lack of resources to travel, inability to transfer

unstable patients to high-volume centers, loss of access to care in areas where low-volume

services are discontinued (particularly rural areas), and resistance by providers to quality

measurement activities. Finally, existing high volume centers may lack the capacity to accept

additional patients. When they do not, further increases in volume could lead to increased rates

of adverse events due to over-stressing the system, as was noted for pediatric trauma.18

Costs of this practice are not explicitly addressed in the IOM report, but widespread

implementation of selective referrals would depend on the collection of detailed and accurate

data (risk adjustment, process, and outcomes data), at substantial cost. Additionally, a

nationwide systematic referral model may require augmenting capability of high-volume

hospitals through additional construction or other major infrastructure investments. Finally, the

travel and inconvenience costs of having patients obtain care at institutions outside the local

community will be borne by either the system or the patients themselves—a cost which may be

compounded further by patients’ and families’ lost productivity.

Comment

Changing practice patterns based on the compelling data linking volume and improved

outcomes is a complex task involving patients, hospitals and communities, as well as payers and

employers. Actually closing hospitals or designating specific health care centers as “magnet”

sites for care of specific illnesses would require, in addition to a wholesale change in health care

systems, major infusions of resources and difficult political choices. For these reasons alone, this

policy decision seems unlikely. Alternatively, hospitals or medical groups may use physicianspecific outcomes information to make decisions about staffing needs (eg, hiring a lower number

of surgeons to ensure that all operators have high volumes), although this too seems unlikely

unless meeting volume thresholds become mandatory or are strongly incentivized.

The Leapfrog Group's efforts represent one of the first major initiatives to use empiric

data to direct selective referrals using volume data. As an initiative begun and carried out within

a specific employer/health care purchaser system it may be limited in its generalizability.

However, prospective evaluation of the effort will yield important information regarding the

costs and outcomes of such a referral system and its impact on patient satisfaction with care.

Outside of the Leapfrog effort, the widespread publication of outcomes, especially

mortality data, has been proposed as a way to help consumers to make more informed health care

choices. A recent systematic review of this paradigm or “strategy” suggests that its impact has

been mixed.20 There are no data to suggest that patients or payers will make major changes in

health care purchasing decisions when provided with volume data alone. To date, press reports

of particularly noteworthy errors seem to have more of an impact on patients' choices of care

than information about volume or even outcomes of care.20,21
209

In addition to the potential use of volume data to guide health care purchasing decisions,

the IOM workshop and authors of the systematic review recommend using volume as one of

several quality measures to initiate local or regional quality improvement efforts. This data may

motivate or inform care improvement efforts at low-volume sites (or those with worse-thanexpected outcomes) through use of site visits, feedback of risk-adjusted outcomes information,

and assessment of care processes. This collaborative approach to quality improvement has been

used successfully in the VA National Surgical Quality Improvement Project22 and in several

projects in New York State.23,24 However, it seems likely that as the volume-outcome

relationship becomes better defined and understood, its influence on the health care choices of

both patients and payers is likely to grow.
210

Table 18.1. Summary of findings from IOM systematic review 17 of volume-outcome

relationship*

Condition Number of

Studies

Reviewed

Comments

Coronary

artery bypass

grafting

9

All studies used appropriate risk adjustment

VOR for both physicians and hospital: 7 studies

Absolute difference in mortality between high- and low-volume

centers and surgeons was 3-10% (NNT 10-33)

Some evidence to suggest that centers and surgeons with good

outcomes experienced increasing volumes over time

(“selective referrals”)

Carotid

endarterectomy 19

Only 9 studies performed adequate risk adjustment

Most studies employed administrative data, making accurate

ascertainment of postoperative stroke impossible

VOR found for surgeon: 9 studies

VOR found for hospital: 7 studies

Absolute difference in mortality between high- and low-volume

hospital/surgeon was 0.2-0.9% (NNT 100-500)

Cancer surgery 20

Risk adjustment methods variable, most are dependent on

administrative data only

VOR most marked for rare cancers/procedures such as pancreatic

resection and esophageal surgery

VOR unclear for common surgery such as colectomy and

pneumonectomy

For esophagectomy, absolute difference in mortality between

high- and low-volume hospitals was 11-13.9% (NNT 7-9)

For pancreatic resection, difference in mortality between high- and

low-volume hospitals gives NNT 10-15

Abdominal

aortic

aneurysm

repair

12

11 studies performed adequate risk adjustment

VOR for hospitals and physicians noted

Absolute reduction in mortality due to surgeon or hospital volume

was 5-9% (NNT 11-20)

“Selective referrals” noted

Pediatric

cardiac

surgery

3

All studies used appropriate risk adjustment

VOR found for both hospital and surgeon volume

Absolute difference in mortality due to surgeon or hospital volume

was 3% (NNT 33)

Possibly greater benefit for more complex/sicker patients

* NNT indicates number needed to treat; VOR, volume-outcome relationship
211

References

1. Luft HS, Bunker JP, Enthoven AC. Should operations be regionalized? The empirical

relation between surgical volume and mortality. N Engl J Med. 1979;301:1364-1369.

2. Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative

mortality for major cancer surgery. JAMA. 1998;280:1747-1751.

3. Glasgow RE, Showstack JA, Katz PP, Corvera CU, Warren RS, Mulvihill SJ. The

relationship between hospital volume and outcomes of hepatic resection for hepatocellular

carcinoma. Arch Surg. 1999;134:30-35.

4. Thiemann DR, Coresh J, Oetgen WJ, Powe NR. The association between hospital volume

and survival after acute myocardial infarction in elderly patients. N Engl J Med.

1999;340:1640-1648.

5. Birkmeyer JD, Lucas FL, Wennberg DE. Potential benefits of regionalizing major surgery

in Medicare patients. Eff Clin Pract. 1999;2:277-283.

6. Dudley RA, Johansen KL, Brand R, Rennie DJ, Milstein A. Selective referral to highvolume hospitals: estimating potentially avoidable deaths. JAMA. 2000;283:1159-1166.

7. Luft HS, Hunt SS, Maerki SC. The volume-outcome relationship: practice-makes-perfect

or selective- referral patterns? Health Serv Res. 1987;22:157-182.

8. Hughes RG, Garnick DW, Luft HS, McPhee SJ, Hunt SS. Hospital volume and patient

outcomes. The case of hip fracture patients. Med Care. 1988;26:1057-1067.

9. Farley DE, Ozminkowski RJ. Volume-outcome relationships and in-hospital mortality: the

effect of changes in volume over time. Med Care. 1992;30:77-94.

10. Hamilton BH, Ho V. Does practice make perfect? Examining the relationship between

hospital surgical volume and outcomes for hip fracture patients in Quebec. Med Care.

1998;36:892-903.

11. Luft HS, Garnick DW, Mark DH, et al. Does quality influence choice of hospital? JAMA.

1990;263:2899-2906.

12. Flood AB, Scott WR, Ewy W. Does practice make perfect? Part I: The relation between

hospital volume and outcomes for selected diagnostic categories. Med Care. 1984;22:98-

114.

13. Luft HS, Hunt SS. Evaluating individual hospital quality through outcome statistics. JAMA.

1986;255:2780-2784.

14. Phillips KA, Luft HS. The policy implications of using hospital and physician volumes as

"indicators" of quality of care in a changing health care environment. Int J Qual Health

Care. 1997;9:341-348.

15. The Leapfrog Group for patient safety: Rewarding higher standards. In: Group TL, ed.

www.leapfrog.org. 2001.

16. Hewitt M. (National Academy of sciences). Interpreting the volume-outcome relationship

in the context of health care quality. 2000.

17. Halm EA, Lee C, Chassin M. (Institute of Medicine). How is volume related to quality in

health care?: A systematic review of the research literature. 2000.

18. Tepas JJ, 3rd, Patel JC, DiScala C, Wears RL, Veldenz HC. Relationship of trauma patient

volume to outcome experience: can a relationship be defined? J Trauma. 1998;44:827-830.

19. Finlayson SR, Birkmeyer JD, Tosteson AN, Nease RF, Jr. Patient preferences for location

of care: implications for regionalization. Med Care. 1999;37:204-209.

20. Marshall MN, Shekelle PG, Leatherman S, Brook RH. The public release of performance

data: what do we expect to gain? A review of the evidence JAMA. 2000;283:1866-1874.
212

21. Mennemeyer ST, Morrisey MA, Howard LZ. Death and reputation: how consumers acted

upon HCFA mortality information. Inquiry. 1997;34:117-128.

22. Khuri SF, Daley J, Henderson W, et al. The Department of Veterans Affairs' NSQIP: the

first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the

measurement and enhancement of the quality of surgical care. National VA Surgical

Quality Improvement Program. Ann Surg. 1998;228:491-507.

23. Chassin MR, Hannan EL, DeBuono BA. Benefits and hazards of reporting medical

outcomes publicly. N Engl J Med. 1996;334:394-398.

24. Coronary Artery Bypass Surgery in New York State, 1992-1994 Albany, NY: New York

State Department of Health. 1996.
213

Chapter 19. Learning Curves for New Procedures – the Case of

Laparoscopic Cholecystectomy

Verna C. Gibbs, MD

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Background

Minimal access surgery began in the early 1980s with the introduction of laparoscopic

fallopian tube ligation. The first laparoscopic cholecystectomy was performed 7 years later, and

was rapidly embraced as the preferred method for cholecystectomy despite a lack of evidence to

support the safety of the new technique.1-6 In response to several deaths and complications

associated with laparoscopic cholecystectomy, the New York State Department of Health issued

guidelines for the credentialing of surgeons who wished to perform the procedure.7,8 At the same

time, a National Institutes of Health Consensus conference published recommendations

regarding indications for laparoscopic cholecystectomy.1

Clinical trials comparing the laparoscopic procedure with other approaches eventually

revealed that the newer procedure to be less morbid than traditional open cholecystectomy, or

even mini-laparotomy.9-16 Importantly, though, it also became clear that acquiring the skills to

perform this new procedure involved a substantial surgical “learning curve.”

17-22 This learning

curve no longer affects patients undergoing laparoscopic cholecystectomy, as training has

become a required part of all surgical residency programs, with graduating surgery residents

typically having performed more than 50 laparoscopic cholecystectomies.23,24 However, the

growth of laparoscopic cholecystectomy has been followed by equally rapid development and

application of minimal access procedures in virtually every surgical specialty. This chapter

considers the patient safety issues that arise with the diffusion of a new procedurally-based

technology. It highlights the “learning curve” inherent in any new procedure, as competence

invariably grows with practice (see Chapter 18). Because it is so widely performed and has the

largest literature describing its record, this chapter focuses on lessons learned from the

introduction of laparoscopic cholecystectomy.

Practice Description

Although there are a wide variety of procedure-specific techniques in minimal access

surgery, all operations utilize videoscopic or digital imaging in conjunction with remote

manipulation. In general, the operator works from two-dimensional, magnified video images of

the operative field while manipulating long narrow instruments placed into the operating cavity

from outside the body. To become proficient in minimal access techniques, the surgeon must

develop skills in interpreting a three-dimensional environment as a two-dimensional image, and

learn how to do familiar tasks (eg, suture) with familiar instruments in an unfamiliar manner.

Importantly, the surgeon never actually touches the tissue being moved with his or her hands.21,25

This loss of tactile input is the major factor in making minimal access techniques difficult to

learn.
214

Prevalence and Severity of the Target Safety Problem

Complications from minimal access procedures fall into 2 general categories: those

directly resulting from the laparoscopic intervention (ie, trocar injuries, dissection injuries,

insufflation-associated events)26 and those associated with the operation itself (eg, bile duct

injury with cholecystectomy, gastric injury with fundoplication).*17-22 For laparoscopic

cholecystectomy, a survey of 1750 surgery department chairpersons reported that bowel and

vascular injuries (laparoscopic-specific injury) occurred in 0.14% and 0.25% of cases

respectively, while the rate of bile duct injuries (procedure-specific) was 0.6%.3

 The bile duct

injury rate was lower at institutions that had performed more than 100 cases. Although this study

was large, as a survey it likely underestimates the true rate of complications. Other multiinstitutional reports of laparoscopic cholecystectomy in the United States have noted a similar

bile duct injury rate and report mortality rates of 0.04% to 0.1%.5,21,25,29 Although undoubtedly

underestimated, even these rates are higher than those associated with open cholecystectomy.

Opportunities for Impact

As set forth above, laparoscopic cholecystectomies is a standard part of surgical

residency training.23,24 Nearly all general surgeons who did not train in the current era have

received postgraduate training in basic laparoscopic techniques. This training often takes the

form of a 2-3 day course involving hands-on experience with animal models and laboratoryskills sessions, then observation or assisting with cases primarily performed by another surgeon,

finally, performing cases supervised by an experienced laparoscopist, and finally performing

cases independently.6,24,30

Proficiency in traditional techniques does not automatically translate to minimal access

methods. We identified one study investigating whether the level of surgical training (attending

surgeon versus chief resident) affected the performance of cholecystectomy.17 This study

suggested that, despite operating on more complex patients, the adverse event rate for surgical

chief residents learning laparoscopic cholecystectomy was similar to that of attending physicians

(who had far more operative experience).

Similarly, skills obtained with one minimal access procedure do not transfer to others.

The operation of laparoscopic fundoplication for gastroesophageal reflux disease entered into

surgical practice after laparoscopic cholecystectomy. Therefore, most surgeons who performed it

had basic laparoscopic skill sets. Studies investigating its implementation suggest a threshold of

25-30 cases before surgeons attain proficiency,31-34 in contrast to a threshold of about 15-20

cases for laparoscopic cholecystectomy.25,29,30,35 In recognition of this lack of transferability,

performing laparoscopic cholecystectomies does not qualify a surgeon to perform laparoscopic

colon resection without first undergoing additional training specifically in laparoscopic colon

techniques.6,36 The need for specific new training has been seen with other procedures as well.37-

41

 

* A third problem concerns the potential adverse effects at the population. While the procedure

itself may be less morbid, the rate at which this ‘safer’ procedure is performed may increase

substantially to the point that the complications experienced by the patient population as a whole

do not decrease.27 This problem has been documented with laparoscopic cholecystectomy,12,28

but processes for improved patient selection have not received sufficient testing to permit review

of a particular safety practice relating to procedure “appropriateness.”
215

Thus, determination of a minimum number of cases required to become proficient (as an

aid to credentialing or proctoring activities), or determining methods to shorten the time needed

to attain this level of skill will have a clear impact on patients undergoing minimal access

procedures. This impact is likely to become greater as the breadth and complexity of procedures

approached through minimal access techniques grows.

Study Designs

Using a structured MEDLINE search, we sought to identify papers that either reported a

threshold number of cases required to attain proficiency, or explicitly compared training

techniques for laparoscopic cholecystectomy in terms of patient outcomes. Our literature search

found a large number of reports describing retrospective analyses or reports from procedure

registries. These studies did not report training protocols, specific physician characteristics or

surgeon-specific volumes, and were therefore excluded from our review. In addition, we found

several review articles.42-44 The first of these reviews focused primarily on statistical techniques

for documenting and analyzing learning curves,42 and the other two43,44 did not meet criteria for

systematic reviews. Nonetheless, the bibliographies of all 3 articles were scanned for relevant

studies.

Study Outcomes

All studies reported clinical outcomes (Level 1), most commonly bile duct injury. Other

complications (eg, insufflation or trocar injuries) were very unusual, and mortality was rare.

Evidence for Effectiveness of the Practice

Three studies specifically addressed the relationship between surgical experience in the

performance of laparoscopic cholecystectomy and a well-defined adverse outcome, bile duct

injury. The first reported 15 bile duct injuries in over 8000 laparoscopic cholecystectomies.30

Multivariate analysis showed that the only significant factor in predicting this adverse event was

the experience of the surgeon (p=0.001). Rapidity of learning was not significantly related to a

surgeon's age, size of practice, or hospital setting. Ninety percent of injuries were predicted to

occur during a surgeon’s first 30 cases. Gigot et al35 reported the incidence of bile duct injury

was 1.3% when the surgeon had performed fewer than 50 cases and 0.35% afterwards (p<0.001).

However, bile duct injuries still occurred with surgeons who had performed >100 cases.35

Similar results have been observed in other studies of bile duct injury with laparoscopic

cholecystectomy,45 suggesting that something beyond the learning curve accounts for many

laparoscopic errors. Examination from error analysis suggests that these events occur because of

visual and perceptual difficulties involved in the operator/equipment interface.46,47

We identified one prospective cohort study from Japan that compared the effectiveness of

2 training courses for laparoscopic cholecystectomy.2

 In this study, one group of 8 surgeons was

assigned to 10 supervised laparoscopic cholecystectomies as part of their initial training; a

second group of 8 surgeons had only 2 observed training sessions. Complications that occurred

over 21 months after completion of the 4 months of training were assessed by means of a

questionnaire sent to all participants. The surgeons who had trained with 10 supervised

procedures had 0.5% major complications (bleeding, bile duct injury or bile leakage) versus 2%

for the surgeons trained with only 2 procedures (p=0.03). The incidence of major complications

occurring during the initial 10 operations was higher among unsupervised surgeons (p=0.005).

Outside of laparoscopic cholecystectomy, we identified one study examining

complication rates of urologic laparoscopic surgeons after completing a 2-day training seminar.48
216

Because the study relied on surveys of participants at 3 and 12 months after course completion, it

is likely biased toward underestimating the incidence of adverse events. Nevertheless the study

showed that surgeons who performed procedures without additional training were 3 times more

likely to have at least one complication compared with surgeons who sought additional training.

Additionally the presence of skilled associates and the development of a surgical team impact

favorably on reducing the number of complications.48,49

Potential for Harm

It is unlikely that the specific introduction of training and requirements for a baseline of

surgical experience in minimal access surgery procedures will lead to adverse events.

Costs and Implementation

In the initial introduction of laparoscopic cholecystectomy most surgeons attended at

least one didactic and hands-on course in operative technique and instrument manipulation.

Some of these experiences included operative procedures in animals and utilization of static

training boxes and devices that may speed the acquisition of perceptual and motor skills. The

need for practice in the development of technical skills is vital, and laboratory courses, training

devices and simulators (Chapter 45) are being tested for their ability to improve operator

skills.50-55 There is insufficient evidence to make a recommendation of the superiority of one

training method over any other and costs are presently undetermined.

After sufficient laboratory experience and practice, it is recommended that the procedure

be performed initially in only carefully selected patients under the supervision of an experienced

surgeon.56-58 How practicing groups of providers obtain an experienced consultant is

variable.59,60 Surgical training fellowships in minimal access surgery have been established and

graduates of these programs have the requisite expertise to supervise others. Unfortunately, such

fellowship graduates are in short supply. Telemedicine may play a role in the mentoring and

technical support for surgeons performing new techniques as it provides a means for remote

performance of a procedure with real-time expert supervision and guidance.61,62

Comment

Minimal access surgery has become extraordinarily popular largely in response to market

forces. The single most important predictor of adverse events in minimal access procedures is

the experience of the provider with the specific operation. Surgeons must acquire the necessary

technical skills and expertise before performing new procedures on patients. Hospitals and

payers should help ensure that providers possess the requisite experience before allowing

procedures to be performed in their facilities or paying for them, since patients alone will

generally be unable to determine surgeon competency.

A number of governing bodies and surgical societies have published guidelines that

outline standards for training for postgraduate surgeons for skill acquisition in minimal access

surgery,1,56-58,63-66 but these recommendations are based more on common sense and clinical

experience than rigorous evidence. It is not known how influential these guidelines are in the

granting of privileges. Continued research is needed to determine the threshold for safe

performance of this and other procedures, the most effective training methods to ensure

competence, and strategies to minimize patient harm while proceduralists gain the experience

they need to be competent and to train others.
217

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a CD-ROM multimedia tutorial in transferring cognitive knowledge essential for

laparoscopic skill training. Am J Surg. 2000;179:320-324.

55. Gallagher AG, McClure N, McGuigan J, Crothers I, Browning J. Virtual reality training in

laparoscopic surgery: a preliminary assessment of minimally invasive surgical trainer

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56. Guidelines for the clinical application of laparoscopic biliary tract surgery. Society of

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57. Guidelines for granting of privileges for laparoscopic and/or thoracoscopic general

surgery. Society of American Gastrointestinal Endoscopic Surgeons (SAGES). Surg

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58. Guidelines for surgical treatment of gastroesophageal reflux disease (GERD). Society of

American Gastrointestinal Endoscopic Surgeons (SAGES). Surg Endosc. 1998;12:186-188.
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clinical practice, education, and research. Surg Endosc. 2000;14:444-447.

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new technology: the physician's learning curve must not harm the patient. Am Surg.

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61. Deaton DH, Balch D, Kesler C, Bogey WM, Powell CS. Telemedicine and endovascular

aortic grafting. Am J Surg. 1999;177:75-77.

62. Moore RG, Adams JB, Partin AW, Docimo SG, Kavoussi LR. Telementoring of

laparoscopic procedures: initial clinical experience. Surg Endosc. 1996;10:107-110.

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65. Guidelines for laparoscopic surgery during pregnancy. Surg Endosc. 1998;12:189-190.

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221

Chapter 20. Prevention of Surgical Site Infections

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Subchapter 20.1. Prophylactic Antibiotics

Background

Surgical site infections (SSI) include superficial incisional infections, infections of the

deep incision space and organ space infections.1,2 A large body of evidence supports the premise

that SSIs can be prevented through administration of appropriate prophylactic antibiotics. Two

national organizations, the Federal Centers for Disease Control and Prevention (CDC) and the

American Society for Health System Pharmacists (ASHP), have recently synthesized this vast

literature to produce comprehensive guidelines regarding the administration of prophylactic

antibiotics across a broad range of procedures.3,4 Because of the breadth of this literature, we

limited the focus of this review of strategies to prevent SSIs to adult surgery and procedures that

typically occur in the operating room (as opposed to procedures such as endoscopy,

interventional cardiology, or radiology procedures).

Practice Description

Antimicrobial prophylaxis refers to a brief course of an antimicrobial agent administered

just before an operation begins in order to reduce intraoperative microbial contamination to a

level that will not overwhelm host defenses and result in infection.4

 To maximize the benefits of

antimicrobial prophylactic, the agent used should be safe, inexpensive, and bactericidal with an

in vitro spectrum that covers the most probable contaminants for the operation.4

 Administration,

usually by intravenous infusion, should be timed so that a bactericidal concentration is present in

serum and tissues by the time the skin is incised.5

 This practice is now standard of care and

recommended by professional societies.6

 Therapeutic levels in serum and tissues should be

maintained until, at most, a few hours after the incision is closed in the operating room.4

Prevalence and Severity of the Target Safety Problem

Surgical site infections are a common complication of care, occurring in 2-5% of patients

after clean extra-abdominal surgeries (eg, thoracic and orthopedic surgery) and in up to 20% of

patients undergoing intra-abdominal procedures.7-12 Studies following patients into the postdischarge period have reported even higher rates of postoperative infection.13-16 These

complications increase morbidity for patients and consume substantial additional resources.17-21

Opportunities for Impact

Approximately 80-90% of surgical patients receive some kind of antibiotic prophylaxis,

though recent studies have shown that choice of regimen, timing of administration or duration of

prophylaxis is inappropriate in approximately 25-50% of cases.22-27
222

Study Designs and Outcomes

As previously noted, the literature on prophylactic antibiotics is extensive. Therefore, the

review was limited to evidence from Level 1A study designs. We identified 9 relevant studies

examining the use of prophylactic antibiotics to prevent surgical site infections: 7 meta-analyses

and 2 systematic reviews.28-36 (Tables 20.1.1 and 20.1.2) These reviews were of high quality and

limited their source material to randomized controlled trials. Although additional randomized

trials have been published since these reviews were performed, updating the results of each

review was beyond the scope of this project. All studies examined measured rates of site

infection directly (Level 1), using previously published definitions to allow comparability. In

addition, the rates of sepsis, length of stay, and physiologic measures were reported. One metaanalysis 31 and one systematic review 33 combined rates of several relevant infectious outcomes.

Evidence for Effectiveness of the Practice

All studies showed a marked reduction in the odds or relative risk of SSI when antibiotic

prophylaxis was employed. None of the meta-analyses reviewed explicitly examined the timing

of prophylaxis, although many studies pooled data from investigations of antibiotic regimens

administered in the immediate preoperative period, (ie, within minutes to an hour of initial

incision). Two meta-analyses in our review29,31 suggested a trend towards lower rates of

infection with use of broader-spectrum antibiotic prophylaxis, such as third generation

cephalosporins. When compared with single dose prophylaxis, multiple dose prophylaxis

generally did not result in significant additional benefit.29,30,35 In fact, Tanos et al found the odds

of SSI were significantly less with single dose prophylaxis.31 Gillespie et al reported a greater

relative risk of infection with single dose prophylaxis with a short-acting antibiotic when

compared with multiple dose prophylaxis.36 However, the risk of infection with single dose

prophylaxis using long-acting antibiotics did not differ significantly from that seen with

multiple-dose regimens.

Potential for Harm

None of the meta-analyses analyzed reported rates of adverse events (such as allergic

reactions or nosocomial infections) associated with antibiotic prophylaxis of any type or

duration. Both of the systematic reviews33,36 noted a trend towards more frequent adverse events

with the use of antibiotic prophylaxis. Authors of both systematic reviews observed that these

events were reported rarely and that variation in the definition of “adverse events” across studies

made pooling results difficult.

Infection with Clostridium difficile affects a large number of hospitalized patients and has

significant clinical and economic implications. As many as 16% of C. difficile colitis cases in

surgical patients can be attributed to prophylaxis alone,37 with higher risk for this complication

among patients receiving broad-spectrum antibiotics or prolonged courses of therapy. Shortening

the duration of antibiotic administration may reduce potential risks of prophylaxis (see Chapter

14). Emergence of other types of resistant pathogens is an additional theoretical concern of

inappropriate antibiotic prophylaxis; our literature search found no data describing effect of

antibiotic prophylaxis on population-level incidence of these pathogens.
223

Costs and Implementation

A number of studies have evaluated strategies for improving compliance with

recommended practices for perioperative antibiotic prophylaxis. These include chart audit with

feedback,38 computerized decision support,23, 39-42 dissemination of guidelines,43 total quality

management (TQM) and continuous quality improvement (CQI) techniques,44-47 provider

education programs,48,49 and comprehensive efforts by an infection control team.50 Another

promising and easily implemented method is to delegate the administration of prophylactic

antibiotics to the anesthesia team or the holding room nursing staff.22, 25, 48

Costs for systems to increase appropriate use of antibiotics will likely be offset by

savings due to prevented infections. However formal analyses of the cost-effectiveness of

specific programs to improve prophylaxis have not been reported.

Comment

For many surgical procedures there is clear evidence supporting the use of antibiotic

prophylaxis, administered in a timely manner, to prevent surgical site infections. The reviews

suggest that broader spectrum antibiotics may be superior to limited-spectrum antibiotics for

intra-abdominal or gynecologic surgeries. In addition, single-dose antibiotic prophylaxis appears

to be at least as effective as multiple-dose regimens for a broad range of surgical procedures and

may pose less risk to patients in terms of adverse events (eg, C. difficile colitis) and less risk to

the population in terms of microbial resistance.

Future research will continue to address what prophylactic regimens are most effective

for various surgical procedures. Investigation should also focus on methods to improve

compliance. The optimal strategies for implementation will likely vary from institution to

institution.
224

Table 20.1.1. Meta-analyses examining antibiotic prophylaxis*

Study Trials

Included

Surgical Procedures,

Antibiotics

Results: Odds Ratio or Relative Risk of

Infection (95% CI)

Kreter,

199235

28 Cardiothoracic surgery;

cephalosporins

 Cefazolin vs. placebo: OR 0.2 (0.10-0.48).

 Cefazolin vs. cefuroxime or cefamandole:

OR 1.6 (1.03-2.45)

• Single dose vs. multiple dose regimen: no

significant difference

McDonal

d, 199830

28 Multiple types of

surgery;

multiple antibiotics

 Single dose vs. multiple dose antibiotics (all

studies): OR 1.06 (0.89-1.25)

 Duration of multiple dose regimen <24

hours: OR 1.02 (0.79-1.32)

• Duration of multiple dose regimen >24

hours: OR 1.08 (0.86-1.36)

Meijer,

199029

42 Biliary surgery;

cephalosporins

 Antibiotic vs. placebo: OR 0.30 (0.23-0.38)

 Cephalosporin I vs. cephalosporin II or III:

OR 1.18 (0.69-2)†

• Single dose vs. multiple dose regimen: OR

0.80 (0.4-1.6)

Mittendor

f, 199328

25 Abdominal

hysterectomy;

multiple antibiotics

 Antibiotic vs. placebo (all studies): OR 0.35

(0.27-0.5); p<0.00001‡

 Cefazolin vs. placebo: OR 0.32 (0.18-0.6);

p=0.0002‡

• Metronidazole vs. placebo: OR 0.24 (0.08-

0.8); p=0.015 ‡

Sharma,

200034

6 Percutaneous

gastrostomy;

multiple antibiotics

 Antibiotic vs. placebo (all studies): RR 0.73,

NNT 5.7

• Single dose regimens: RR 0.78, NNT 6.1

Tanos,

199431

17 Abdominal

hysterectomy;

cephalosporins

 Antibiotic vs. placebo (all studies): OR 0.35

(0.3-0.4)

 Cephalosporin I vs. placebo: OR 0.4 (0.3-

0.5)

 Cephalosporin II vs. placebo: OR 0.37 (0.2-

0.8)

 Cephalosporin III vs. placebo: OR 0.26 (0.1-

0.5)
225

• Single dose vs. multiple dose regimen: OR

0.37 (0.3-0.5)

Wilson,

199251

21 Multiple types of

surgery;

multiple antibiotics

 Amoxicillin-clavulanic acid vs. other

antibiotics (all studies): OR 0.84 (0.68-

1.04)

 Trend favoring amoxicillin-clavulanic acid

for biliary and gynecologic surgery

* CI indicates confidence interval; NNT, number needed to treat; OR, odds ratio, and RR,

relative risk.

† Roman numerals I, II, III indicate generation of cephalosporin antibiotics.

‡ P values were reported in article; OR were approximated based on figures.
226

Table 20.1.2. Systematic reviews of antibiotic prophylaxis*

Study Trials

Included

Surgical

Procedures;

Antibiotics

Results: Relative Risk of Infection (95% CI)

Gillespie,

200036

48 Long bone

fractures;

multiple

antibiotics

Single dose antibiotic vs. placebo 

Deep wound infection: RR 0.40 (0.24-0.67)

Superficial wound infection: RR 0.69 (0.50-0.95)

Urinary tract infection: RR 0.63 (0.53-0.76)

Pneumonia: RR 0.46 (0.33-0.65)

Multiple dose antibiotic vs. placebo:

Deep wound infection: RR 0.36 (0.21-0.65)

Superficial wound infection: RR 0.48 (0.28-0.81)

Urinary tract infection: RR 0.66 (0.4-1.0)

Pneumonia: RR 0.81 (0.41-1.63)

Adverse events: RR 1.83 (0.96-3.50)

Single dose short-acting antibiotic vs. multiple doses same

agent up to 24 hours after surgery

Deep wound infection: RR 7.98 (1.01-62.0)

Superficial wound infection: RR 4.82 (1.08-21.6)

Urinary tract infection: RR 1.81 (1.01-3.23)

Single dose long-acting antibiotic vs. any multiple dose

regimen lasting more than 24 hours 

Deep wound infection: RR 1.10 (0.22-5.34)

Superficial wound infection: RR 0.57 (0.17-1.93)

Multiple doses administered over 24 hours or less vs.

longer therapy

Deep wound infection: RR 1.1 (0.22-5.34)

Superficial wound infection: RR 0.57 (0.17-1.93)

Oral vs. parenteral prophylaxis 

Insufficient data (single underpowered study)

Smaill,

200033

66 Cesarean section;

multiple

antibiotics

Impact of antibiotic prophylaxis on ...

-Combined outcomes of fever, wound infection, sepsis and

endometritis:

Elective Cesarean section: RR 0.25 (0.11-0.55)

Emergent Cesarean section: RR 0.39 (0.33-0.46)

Unspecified/nonelective: RR 0.37 (0.32-0.42)
227

All Cesarean section: RR 0.37 (0.33-0.42)

-Maternal side effects: RR 1.96 (0.86-4.49)

-Length of stay: 0.34 fewer days in hospital (0.17-0.52)

* CI indicates confidence interval; RR, relative risk.
228

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231

Subchapter 20.2. Perioperative Normothermia

Background

The body temperature of patients may fall by 1 to 1.5°C during the first hour of general

anesthesia.1

 Regional anesthesia also typically causes core hypothermia.2 Intraoperative

hypothermia impairs immune function (especially oxidative killing by neutrophils) and results in

dermal vasoconstriction and reduced blood flow to surgical sites, which further increases the risk

of surgical site infection by lowering tissue oxygen tension.3

 Hypothermia also results in reduced

platelet function, shivering associated with patient discomfort and activation of the sympathetic

nervous system, and adverse cardiac events.2

Practice Description

Normal core temperature can be maintained during surgery through use of active

measures including warmed intravenous fluids and inspired gases, as well as forced air warming.

The latter involves an air blanket placed over the patient that circulates air warmed to 40°C.

Water blankets may also be used, but are not as effective in maintaining body temperature.4

Patient temperature is monitored using conventional thermometer probes, with active measures

adjusted to maintain core temperature near 36.5°C. Any method or combination of methods that

maintains the target core temperature appears to have the same effect.2

Prevalence and Severity of the Target Safety Problem

See Subchapter 20.1.

Opportunities for impact

Attention to patient temperature is standard of care in intraoperative anesthesia

management.*

 However, there are no data on the extent to which active warming measures are

currently used perioperatively.

 

* The American Society of Anesthesiologists’ Standards for Basic Anesthesia Monitoring notes

“Every patient receiving anesthesia shall have temperature monitored when clinically significant

changes in body temperature are intended, anticipated or suspected.”

5
232

Study Designs and Outcomes

We identified one randomized controlled trial3

 and one retrospective cohort study6

evaluating the effect of active warming interventions on the rate of wound infection (Level 1

outcome). (Table 20.2.1). Wound infection was either defined as “suppuration requiring removal

of sutures”

3

 or as in previously published definitions.7

Evidence for Effectiveness of the Practice

Kurz et al performed a randomized controlled trial of active warming in the

intraoperative care of patients undergoing elective colectomy. All patients received aggressive

perioperative hydration and intravenous opioids for pain relief, in an effort to maximize wound

perfusion. Patients in the normothermia arm experienced a 68% reduction in the rate of wound

infection, lower wound infection scores (as defined by the elements of the acronym ASEPSIS:

Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues,

Isolation of bacteria, and duration of inpatient Stay), and shorter length of hospitalization.3

While the relatively high infection rate (19% of control group in this university-based population

with a substantial degree of underlying disease) and suboptimal antibiotic prophylaxis

(antibiotics continued for about 4 days postoperatively; see Subchapter 20.1) do not invalidate

the study results, they do limit their generalizability.

In a retrospective cohort study based on chart reviews of 150 patients undergoing elective

colectomy, Barone et al noted no independent association between intraoperative hypothermia

(defined as temperature less than <34.3oC) and the incidence of wound infections, or the length

of stay. Explanation for differences in the findings of the two studies may relate to confounding

due to the retrospective design of the study by Barone, or in differences in defining wound

infections by the authors (suppuration requiring removal of sutures).8

Other potential benefits of maintaining perioperative normothermia have been reported in

randomized controlled trials. Frank et al found the risk of morbid cardiac events (combined

outcome of angina, myocardial ischemia or infarction, and ventricular arrhythmia) was

significantly decreased among patients in the normothermia group (1% intervention vs. 6%

control, p=0.02).9

 Maintaining normothermia has also been associated with decreased blood loss

and transfusion requirements among patients undergoing elective colectomy3

 and hip

arthroplasty.10,11 Postoperative shivering, thermal discomfort, time to extubation, and duration of

post-anesthesia recovery are all significantly reduced.2,12

Potential for Harm

None of these studies reported an adverse effect directly related to these practices. Sigg et

al observed a higher rate of wound bacterial colonization with the reuse of forced air coverlets.13

Costs and Implementation

Equipment for monitoring temperature is readily available in operating rooms. Kruz et al

estimated the direct cost of fluid and forced air warming at $30 per case.9

 Studies have not

formally assessed all relevant costs, including additional physician time required. It is likely that

added costs are largely offset by savings due to reduced surgical site infections and associated

decreases in length of stay.
233

Comment

Given the evidence of effectiveness, the low potential for harm, and the simplicity of the

intervention (including the ready availability of the equipment), maintenance of perioperative

normothermia seems a promising practice to improve patient safety. The methodologically

stronger of the 2 studies reviewed showed clear benefits. However, some of its benefits may not

be generalizable to patient populations undergoing other procedures. For example, intraoperative

hypothermia may have little impact on wound infections in patients undergoing cesarean

section.14 Thus, additional study of the practice is needed in other settings. Furthermore, for

some procedures hypothermia is likely to protect patients. Core temperature is often intentionally

reduced to protect the myocardium and central nervous system during certain cardiac and

neurosurgical procedures.2,12,15 In such cases the potential benefits of normothermia may not

outweigh the associated risks.

Table 20.2.1. Summary of studies reporting effectiveness of perioperative normothermia*

Study Study Population; Intervention Study Design, 

Outcomes

Results

Kurz,

19963

200 patients (104 normothermia, 96

hypothermia) undergoing, elective

colectomy in multicenter study;

warmed gases, fluids and forced arm

during operation vs. usual care

Level 1,

Level 1

Wound infection rate: 6% vs. 19%

(p=0.009)

ASEPSIS score: 7 vs. 13 (p=0.002)

Days to sutures out: 9.9 vs. 10.9

(p=0.002)

Taking nutrition orally: 5.6 vs. 6.5 days

(p=0.006)

Length of stay: 12 vs. 15 days (p=0.001)

Barone,

19996

150 patients (101 normothermia, 49

hypothermia) undergoing elective

colectomy at a single community

hospital; no formal intervention

(retrospective chart review,

warming devices were used in 90%

of patients)

Level 3,

Level 1

Wound infection rate: 12% in both

groups

Multivariate models: no significant

association between hypothermia

and wound infection or length of

stay

* ASEPSIS indicates Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of

deep tissues, Isolation of bacteria, and duration of inpatient Stay.7

References

1. Matsukawa T, Sessler DI, Sessler AM, et al. Heat flow and distribution during induction of

general anesthesia. Anesthesiology. 1995;82:662-673.

2. Sessler DI. Mild perioperative hypothermia. N Engl J Med. 1997;336:1730-1737.

3. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of

surgical-wound infection and shorten hospitalization. Study of Wound Infection and

Temperature Group. N Engl J Med. 1996;334:1209-1215.
234

4. Kurz A, Kurz M, Poeschl G, Faryniak B, Redl G, Hackl W. Forced-air warming maintains

intraoperative normothermia better than circulating-water mattresses. Anesth Analg.

1993;77:89-95.

5. American Society of Anesthesiologists. Standards of the American Society of

Anesthesiologists. Available at: http://www.asahq.org/Standards/02.html. Accessed June 6,

2001.

6. Barone JE, Tucker JB, Cecere J, et al. Hypothermia does not result in more complications

after colon surgery. Am Surg. 1999;65:356-359.

7. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for

postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet.

1986;1:311-313.

8. Sessler DI, Kurz A, Lenhardt R. Re: Hypothermia reduces resistance to surgical wound

infections. Am Surg. 1999;65:1193-1196.

9. Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia

reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA.

1997;277:1127-1134.

10. Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A. Mild hypothermia increases blood loss

and transfusion requirements during total hip arthroplasty. Lancet. 1996;347:289-292.

11. Winkler M, Akca O, Birkenberg B, et al. Aggressive warming reduces blood loss during

hip arthroplasty. Anesth Analg. 2000;91:978-984.

12. Leslie K, Sessler DI. The implications of hypothermia for early tracheal extubation

following cardiac surgery. J Cardiothorac Vasc Anesth. 1998;12:30-34; discussion 41-34.

13. Sigg DC, Houlton AJ, Iaizzo PA. The potential for increased risk of infection due to the

reuse of convective air-warming/cooling coverlets. Acta Anaesthesiol Scand. 1999;43:173-

176.

14. Munn MB, Rouse DJ, Owen J. Intraoperative hypothermia and post-cesarean wound

infection. Obstet Gynecol. 1998;91:582-584.

15. Winfree CH, Baker KZ, Connollly ES. Perioperative normothermia and surgical-wound

infection. N Engl J Med. 1996;335:749.

Subchapter 20.3. Supplemental Perioperative Oxygen

Background

Low oxygen content in devitalized tissues predisposes them to bacterial colonization,

which is thought to be a key pathophysiologic step in the initiation of surgical site infections.1

Administration of high concentrations of oxygen increases wound oxygen tension, allowing for

more effective neutrophil function and the potential for reduced infection rates.2

Practice Description

The practice of perioperative oxygen supplementation involves administration of 80%

oxygen and 20% nitrogen by endotracheal tube intraoperatively and by sealed mask and

manifold system or conventional non-rebreather mask for the first two hours of recovery.

Oxygen is increased to 100% immediately before extubation, with the concentration returned to

80% as soon as deemed safe by the anesthesiologist.3

Prevalence and Severity of the Target Safety Problem

See Subchapter 20.1.
235

Opportunities for Impact

Administration of oxygen is a routine part of perioperative care. However the frequency

with which high oxygen concentrations (as described above) are administered is not known.

Study Designs and Outcomes

We identified one randomized controlled trial evaluating the effect of high concentration

oxygen supplementation on surgical site infections (Table 20.3.1).3

 The primary outcome was

incidence of wound infection within 15 days after surgery (Level 1). Wounds were considered

infected when bacteria were cultured from pus expressed from the incision or aspirated from a

loculated collection within the wound.3

Evidence for Effectiveness of the Practice

The clinical characteristics of the intervention and control groups were similar at

baseline, including risk of infection as assessed by a modified Study on the Efficacy of

Nosocomial Infection Control (SENIC) score (p=0.8) and National Nosocomial Infection

Surveillance System (NNISS) score (p=0.86). The incidence of wound infection was

significantly less in the intervention group (13/250, 5%) than in the control group (28/250, 11%,

p=0.014). The results remain statistically significant when the study definition of “infection” is

broadened to include wounds with pus but no bacterial growth on culture (7% vs. 14%,

p=0.012). Perioperative administration of high levels of oxygen was associated with a 54%

relative risk reduction (95% CI: 12%-75%) of wound infection within 15 days of surgery.

ASEPSIS (Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of

deep tissues, Isolation of bacteria, and duration of inpatient Stay4

) scores were also significantly

better with high levels of oxygen (3 vs. 5, p=0.01). Although longer follow-up might have

identified additional wound infections, the authors argue that it was unlikely that these events

would take place preferentially in one group as the proposed therapeutic effect of oxygen

appears limited to the immediate perioperative period.3

 Admission to the intensive care unit and

death were less frequent in the intervention group, but the difference failed to achieve statistical

significance.

Two additional randomized controlled trials of perioperative supplemental oxygen were

identified.5,6 Both found a significant reduction in postoperative nausea and vomiting, but neither

study evaluated the effect on wound infections.

Potential for Harm

The study by Greif et al reported no adverse affects related to the intervention. Several

potential risks of high oxygen concentrations should be noted. High oxygen concentrations may

present a fire hazard when heated surgical instruments (eg, lasers) are introduced into the

airway.7-11 Such concentrations can also induce lung injury in certain vulnerable patients12 or

precipitate atelectasis in patients at risk.3,13,14 Hyperoxic mixtures may increase oxidative

myocardial injury in patients undergoing cardiopulmonary bypass.15 Finally, patients who

undergo resuscitation with 100% oxygen may have worsened neurologic outcomes, possibly also

as a result of increased oxygen free-radical generation.16,17

Costs and Implementation

The incremental direct costs associated with administering high oxygen concentrations

are minimal, as oxygen delivery systems are elements of routine perioperative care and employ

equipment readily available in operating rooms.
236

Comment

Administration of perioperative oxygen in high concentrations seems a promising

adjunctive therapy: the practice is simple, the equipment needed is readily available, and a

multicenter randomized trial has demonstrated its efficacy.

 However, there are significant questions about the generalizability of the approach to

expanded populations of surgical patients. All patients in the Grief et al study had core

temperature maintained at 36oC, were aggressively hydrated, and had postoperative pain treated

with opioids in order to maximize wound perfusion. To what degree the effectiveness of the

practice is affected by changes in these “co-interventions” has not been assessed. There is reason

for concern regarding use of high concentrations of oxygen in patients undergoing procedures

associated with low blood flow (eg, cardiopulmonary bypass), or in whom local production of

oxygen free radicals may cause further organ injury (eg, patients with head trauma).

Additionally, questions remain regarding whether modifications to the protocol used

would impart similar or greater benefit. For example, would oxygen administration by nasal

cannula at 10 LPM be as effective as oxygen delivered by a sealed mask? Would longer duration

of therapy impart additional benefit? These questions should be answered in future trials.

Table 20.3.1. Randomized controlled trial of supplemental perioperative oxygen*

Study Study Population Intervention Results†

Greif,

20003

500 patients

undergoing colorectal

resection; multicenter

study, 1996-98

80% oxygen, 20%

nitrogen during surgery

and the first 2 hours of

recovery

Wound infection:

ARR 0.06 (95% CI, 0.018-0.102)

RR 0.46 (95% CI, 0.25-0.88)

ASEPSIS§

 score: 3 vs. 5 (p=0.01)

ICU admission: 2.0% vs. 4.8%

(p=0.14)

Mortality: 0.4% vs. 2.4% (p=0.13)

* ARR indicates absolute risk reduction; CI, confidence interval; ICU, intensive care unit; and

RR, relative risk. The ASEPSIS scoring system incorporates Additional treatment, Serous

discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and

duration of inpatient Stay4

.

† Outcomes within 15 days of surgery, expressed as rates in intervention vs. control groups.

References

1. Hopf HW, Hunt TK, West JM, et al. Wound tissue oxygen tension predicts the risk of

wound infection in surgical patients. Arch Surg. 1997;132:997-1004.

2. Hopf H, Sessler DI. Routine postoperative oxygen supplementation. Anesth Analg.

1994;79:615-616.

3. Greif R, Akca O, Horn EP, Kurz A, Sessler DI. Supplemental perioperative oxygen to

reduce the incidence of surgical- wound infection. Outcomes Research Group. N Engl J

Med. 2000;342:161-167.

4. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for

postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet.

1986;1:311-313.
237

5. Greif R, Laciny S, Rapf B, Hickle RS, Sessler DI. Supplemental oxygen reduces the

incidence of postoperative nausea and vomiting. Anesthesiology 1999;91:1246-1252.

6. Goll V, Akca O, Greif R, et al. Ondansetron is no more effective than supplemental

intraoperative oxygen for prevention of postoperative nausea and vomiting. Anesth Analg.

2001;92:112-117.

7. Healy GB. Complications of laser surgery. Otolaryngol Clin North Am. 1983;16:815-820.

8. Hunsaker DH. Anesthesia for microlaryngeal surgery: the case for subglottic jet

ventilation. Laryngoscope. 1994;104:1-30.

9. Aly A, McIlwain M, Duncavage JA. Electrosurgery-induced endotracheal tube ignition

during tracheotomy. Ann Otol Rhinol Laryngol. 1991;100:31-33.

10. Barnes AM, Frantz RA. Do oxygen-enriched atmospheres exist beneath surgical drapes

and contribute to fire hazard potential in the operating room? Aana J. 2000;68:153-161.

11. de Richemond AL, Bruley ME. Use of supplemental oxygen during surgery is not risk free.

Anesthesiology. 2000;93:583-584.

12. Donat SM, Levy DA. Bleomycin associated pulmonary toxicity: is perioperative oxygen

restriction necessary? J Urol. 1998;160:1347-1352.

13. Akca O, Podolsky A, Eisenhuber E, et al. Comparable postoperative pulmonary atelectasis

in patients given 30% or 80% oxygen during and 2 hours after colon resection.

Anesthesiology. 1999;91:991-998.

14. Lentschener C. Prevention of atelectasis during general anaesthesia. Lancet. 1995;346:514-

515.

15. Ihnken K, Winkler A, Schlensak C, et al. Normoxic cardiopulmonary bypass reduces

oxidative myocardial damage and nitric oxide during cardiac operations in the adult. J

Thorac Cardiovasc Surg. 1998;116:327-334.

16. Zwemer CF, Whitesall SE, D'Alecy LG. Cardiopulmonary-cerebral resuscitation with

100% oxygen exacerbates neurological dysfunction following nine minutes of

normothermic cardiac arrest in dogs. Resuscitation. 1994;27:159-170.

17. Rubertsson S, Karlsson T, Wiklund L. Systemic oxygen uptake during experimental

closed-chest cardiopulmonary resuscitation using air or pure oxygen ventilation. Acta

Anaesthesiol Scand. 1998;42:32-38.

Subchapter 20.4. Perioperative Glucose Control

Background

Diabetes is a well-known risk factor for perioperative medical complications. Poor

glucose control is an independent risk factor for surgical site infections1-5 in a range of surgical

procedures. Increased risk for infection is thought to result from a combination of clinically

apparent effects of longstanding hyperglycemia (eg, macro- and microvascular occlusive

disease) and subtle immunologic defects, most notably neutrophil dysfunction.6-12

Hyperglycemia may also impair the function of complement and antibodies, reducing the

opsonic potential of these factors and impairing phagocytosis, further reducing barriers to

infection.13,14 Although many of the clinically apparent manifestations of diabetes are not easily

reversed in the perioperative period, there is a small literature that suggests that improving

glucose control can improve immunologic function and reduce the incidence of surgical site

infections (SSI).6-8,12
238

Perioperative management of glucose for diabetic patients commonly includes

withholding or administering a reduced dose of the patients’ usual hypoglycemic agent(s) and

commencing a low-rate intravenous glucose infusion while patients are NPO prior to surgery.

The infusion is continued postoperatively until the patient is able to eat and resume outpatient

diabetes therapy. Often a sliding scale insulin regimen, a schedule of subcutaneous regular

insulin dosage contingent on capillary blood glucose measurements, is also continued through

the perioperative period. However, use of a sliding scale may result in wide variations in serum

glucose,15 opening the rationale of this method to question.16-18

Practice description

Aggressive glucose control in the perioperative period can be achieved using a

continuous intravenous insulin infusion (CII). Nursing staff monitor fingerstick (or arterial line

drop-of-blood sample) glucose measurements and adjust the infusion rate based on a protocol

intended to maintain serum glucose within a certain range. For example, the target range for the

original Portland Protocol was between 151 and 200 mg/dL.16,19,20 In the most recent version, the

range is between 125 and 175 mg/dL.21

Prevalence and Severity of the Target Safety Problem

Little evidence exists to describe the practice of CII in prevention of surgical site

infections in broad surgical practice. The small amount of evidence available describes its use in

patients undergoing cardiac surgery, primarily coronary artery bypass grafting (CABG).

Diabetes is a well-described risk factor for sternal wound infections, a catastrophic complication

of median sternotomy.19,22-25 Sternal wound infections occur in 0.8% to 2% of unselected

patients undergoing median sternotomy and CABG.20,22,23 Diabetic patients, who comprise

between 17 and 20% of all patients undergoing CABG, have been reported to have an incidence

of sternal wound infections as high as 5.6%.26 Such infections are associated with marked

increases in morbidity and costs. Furnary et al reported that patients with sternal wound

infections had an average increased length of stay of 16 days and a higher mortality rate (19%

vs. 3.8% in patients without sternal wound infections).20 (See also Subchapter 20.1).

Opportunities for Impact

More than 700,000 Americans underwent open-heart surgery in 1998 alone.27 Up to 20%

of these patients may be candidates for continuous insulin infusion. Although CII is included in

the recent ACC/AHA Guidelines for CABG Surgery,28 there are no data on the extent to which

the measure is currently used during cardiac or other surgical procedures.

Study Designs and Outcomes

We identified one prospective before-after study that compared rates of deep sternal

wound infections (DSWI) in diabetic patients undergoing CABG before and after

implementation of an aggressive CII protocol.20 DSWI included infections involving the sternum

or mediastinal tissues, including mediastinitis. An older study from the same authors was not

reviewed as it reported findings at an earlier point in the same trial.19 Additional studies

examined the use of CII in perioperative patients but did not report Level 1 clinical outcomes

relevant to patient safety (eg, mortality, wound infection) and were also not reviewed.29
239

Evidence for Effectiveness of the Practice

Furnary et al found that aggressive glucose control with CII was associated with a

reduction in deep sternal wound infections.20 The effect of the intervention remained statistically

significant in a logistic regression model adjusting for multiple potential confounding variables.

Furthermore, the demographic characteristics were generally biased against the CII group, which

had a significantly higher percentage of patients with hypertension, renal insufficiency, and

obesity but fewer patients with congestive heart failure. However, the authors did not adjust for

long-term markers of glucose control such as glycosylated hemoglobin, nor did they describe

other changes in patient care systems that resulted from changing patients to insulin infusions.

Continuous insulin infusions require closer attention by nursing staff both for monitoring of

infusion equipment and for frequent measurements of blood glucose. It is possible that the

improved outcomes were due to closer overall attention to the patient. Although 74% of DSWI

occurred after initial discharge (raising the concern that the shorter length of stay in the sliding

scale insulin group may have resulted in some infection not being detected), the authors reported

that they directly followed-up all diabetic patients for one year from the time of surgery.30 The

personnel, equipment, surgical techniques, and use of prophylactic antibiotics were similar

throughout the study period.31 Nonetheless, it is likely that secular trends in the care of patients

undergoing cardiac surgery account for some of the impact attributed to CII.

Potential for Harm

Hypoglycemic episodes are the most concerning adverse event associated with intensive

glucose management with intravenous insulin. These episodes result in a range of medical

complications, from delirium to myocardial infarction resulting from increased sympathetic

activity. Furnary noted that, using the standardized protocol in their study, no cases of

symptomatic hypoglycemia occurred in either group of patients.30 However, CII protocols

intended to maintain normoglycemia in surgical patients have been associated with high rates

(40%) of postoperative hypoglycemia requiring treatment (<60 mg/dL glucose).32

Costs and Implementation

The equipment and personnel required to administer intravenous insulin are readily

available. Although a formal cost-effectiveness analysis of the practice has not yet been

performed, limited data are available. Furnary et al estimate the additional expense of CII at

$125-150 per patient.33 While this likely includes direct costs of CII such as infusion equipment

and additional nursing care for more frequent monitoring of glucose and adjustment of insulin

infusion rates, it may underestimate the true costs of the practice at other sites, particularly

during early phases of implementation. Furnary reported that the practice required a significant

period of time for staff to gain familiarity and expertise with CII, and that by the end of the study

they had in place a system that required no significant changes in care patterns for CII to be

administered.34 In early phases of implementation there may be additional costs related to excess

time spent by patients in ICU or high-level care areas (ie, stepdown units) rather than regular

wards. The start-up costs in terms of training and system changes, and whether the approach is

easily adaptable to sites that lack the capability to administer CII in numerous inpatient settings,

have yet to be determined.

It seems likely that savings from averted infections may substantially compensate for the

incremental direct costs of CII. Based on Furnary's findings and cost assumptions, the average

DSWI was associated with $26,000 in additional charges (not costs). Of 1499 patients in the
240

intervention group, the number of DSWIs prevented was 10 (95% CI: 4-21) and the average cost

to prevent one DSWI was approximately $21,000 (95% CI: $10,000-$52,500). Of course, these

figures do not incorporate the potential effects of the intervention on other sites of infection,

mortality, adverse events, and patients’ preferences (utilities) for these possible health states.

Comment

An increasing body of evidence demonstrates that tight control of blood glucose

improves overall outcomes of patients with diabetes.35-37 Emerging data, coupled with an

increasing appreciation of the deleterious effects of hyperglycemia on immune function, strongly

support the supposition that aggressive control of perioperative glucose reduces the incidence of

surgical site infections. Although the practice has been implemented at a number of institutions

and is also being used in diabetic patients undergoing non-cardiac surgeries,34 studies of its

effectiveness in these settings have not yet been published. Until additional evidence is available,

preferably from blinded randomized controlled trials, the intervention can be considered

promising but not yet proven to be causally associated with improved outcomes.
241

Table 20.4.1. Prospective, before-after study of aggressive perioperative glucose control*

Study Study

Population

Comparison Groups Results†

Furnary,

199920

2467 diabetic

patients

undergoing

cardiac

surgery at a

community

hospital

968 patients treated with

sliding scale SQ insulin

(1987-91)

1499 patients treated with

CII to target glucose of

150-200 mg/dL until

POD 3 (1991-97)

Deep surgical wound infections

Unadjusted: 1.9% vs. 0.8% (p=0.011)

Adjusted RR 0.34 (95% CI: 0.14-0.74)

Mortality: 6.1% vs. 3.0% (p=0.03)

Length of Stay: 10.7d vs. 8.5d (p<0.01)

* CI indicates confidence interval; CII, continuous intravenous insulin; POD, postoperative day;

and RR, relative risk.

† Results reported as pre-intervention (sliding scale SQ insulin) vs. post-intervention (CII).

References

1. Medina-Cuadros M, Sillero-Arenas M, Martinez-Gallego G, Delgado-Rodriguez M.

Surgical wound infections diagnosed after discharge from hospital: epidemiologic

differences with in-hospital infections. Am J Infect Control. 1996;24:421-428.

2. Kanat A. Risk factors for neurosurgical site infections after craniotomy: a prospective

multicenter study of 2944 patients. Neurosurgery. 1998;43:189-190.

3. Moro ML, Carrieri MP, Tozzi AE, Lana S, Greco D. Risk factors for surgical wound

infections in clean surgery: a multicenter study. Italian PRINOS Study Group. Ann Ital

Chir. 1996;67:13-19.

4. Barry B, Lucet JC, Kosmann MJ, Gehanno P. Risk factors for surgical wound infections in

patients undergoing head and neck oncologic surgery. Acta Otorhinolaryngol Belg.

1999;53:241-244.

5. Richet HM, Chidiac C, Prat A, Pol A, David M, Maccario M, et al. Analysis of risk factors

for surgical wound infections following vascular surgery. Am J Med. 1991;91:170S-72S.

6. Marhoffer W, Stein M, Schleinkofer L, Federlin K. Monitoring of polymorphonuclear

leukocyte functions in diabetes mellitus–a comparative study of conventional radiometric

function tests and low-light imaging systems. J Biolumin Chemilumin. 1994;9:165-170.

7. Terranova A. The effects of diabetes mellitus on wound healing. Plast Surg Nurs.

1991;11:20-25.

8. Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, et al. Wound

hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg.

1997;132:991-996.

9. Nolan CM, Beaty HN, Bagdade JD. Further characterization of the impaired bactericidal

function of granulocytes in patients with poorly controlled diabetes. Diabetes.

1978;27:889-894.

10. Bagdade JD, Walters E. Impaired granulocyte adherence in mildly diabetic patients: effects

of tolazamide treatment. Diabetes. 1980;29:309-311.
242

11. Mowat A, Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with

diabetes mellitus. N Engl J Med. 1971;284:621-627.

12. MacRury SM, Gemmell CG, Paterson KR, MacCuish AC. Changes in phagocytic function

with glycaemic control in diabetic patients. J Clin Pathol. 1989;42:1143-1147.

13. Hennessey PJ, Black CT, Andrassy RJ. Nonenzymatic glycosylation of immunoglobulin G

impairs complement fixation. JPEN J Parenter Enteral Nutr. 1991;15:60-64.

14. Black CT, Hennessey PJ, Andrassy RJ. Short-term hyperglycemia depresses immunity

through nonenzymatic glycosylation of circulating immunoglobulin. J Trauma.

1990;30:830-832.

15. Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in

medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157:545-552.

16. Zinman B. Insulin regimens and strategies for IDDM. Diabetes Care. 1993;16(Suppl 3):24-

28.

17. Kletter GG. Sliding scale fallacy. Arch Intern Med. 1998;158:1472.

18. Shagan B. Does anyone here know how to make insulin work backwards? Why sliding

scale insulin coverage doesn't work. Pract Diabetol. 1990;9:1-4.

19. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control

lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac

Surg. 1997;63:356-361.

20. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion

reduces the incidence of deep sternal wound infection in diabetic patients after cardiac

surgical procedures. Ann Thorac Surg. 1999;67:352-360.

21. Starr Wood Cardiac Group. Starr Wood Research - Continuous Intravenous Insulin

Infusion. Available at: http://www.starrwood.com/research/insulin.html. Accessed June 11,

2001.

22. Borger MA, Rao V, Weisel RD, Ivanov J, Cohen G, Scully HE, et al. Deep sternal wound

infection: risk factors and outcomes. Ann Thorac Surg. 1998;65:1050-1056.

23. Trick WE, Scheckler WE, Tokars JI, Jones KC, Reppen ML, Smith EM, et al. Modifiable

risk factors associated with deep sternal site infection after coronary artery bypass grafting.

J Thorac Cardiovasc Surg. 2000;119:108-114.

24. Zacharias A, Habib RH. Factors predisposing to median sternotomy complications. Deep

vs superficial infection. Chest. 1996;110:1173-1178.

25. Whang W, Bigger JT. Diabetes and outcomes of coronary artery bypass graft surgery in

patients with severe left ventricular dysfunction: results from The CABG Patch Trial

database. The CABG Patch Trial Investigators and Coordinators. J Am Coll Cardiol.

2000;36:1166-1172.

26. Golden SH, Peart-Vigilance C, Kao WH, Brancati FL. Perioperative glycemic control and

the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care.

1999;22:1408-1414.

27. American Heart Association. 2001 Heart and Stroke Statistical Update. Available at:

http://www.americanheart.org/statistics/medical.html. Accessed June 11, 2001.

28. Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, et al. ACC/AHA

Guidelines for Coronary Artery Bypass Graft Surgery: A Report of the American College

of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee

to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). American

College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999;34:1262-

1347.
243

29. Lazar HL, Chipkin S, Philippides G, Bao Y, Apstein C. Glucose-insulin-potassium

solutions improve outcomes in diabetics who have coronary artery operations. Ann Thorac

Surg. 2000;70:145-150.

30. Furnary AP. Continuous intravenous insulin infusion reduces the incidence of deep sternal

wound infection in diabetic patients after cardiac surgical procedures [discussion]. Ann

Thorac Surg. 1999;67:360-62.

31. CTSNet, the Cardiothoracic Surgery Network. Use of historical controls may weaken

conclusions. Available at: Available at: http:www.ctsnet.org/forum/78/0/2240. Accessed

June 18, 2001.

32. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Attempting to maintain

normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative

hypoglycemia. Anesth Analg. 1999;89:1091-1095.

33. Star Wood Cardiac Group. The Portland Insulin Protocol - Frequently Asked Questions

Page 1. Available at: http://www.starrwood.com/research/Insulin_FAQ1.html. Accessed

June 11, 2001.

34. Starr Wood Cardiac Group. The Portland Insulin Protocol - Frequently Asked Questions

Page 2. Available at: http://www.starrwood.com/research/Insulin_FAQ2.html. Accessed

June 11, 2001.

35. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. The Diabetes Control and

Complications Trial Research Group. N Engl J Med. 1993;329:977-986.

36. The effect of intensive diabetes therapy on the development and progression of neuropathy.

The Diabetes Control and Complications Trial Research Group. Ann Intern Med.

1995;122:561-568.

37. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of

intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of

Diabetes Interventions and Complications Research Group. N Engl J Med. 2000;342:381-

389.
244
245

Chapter 21. Ultrasound Guidance of Central Vein Catheterization

Jeffrey M. Rothschild, MD, MPH

Harvard Medical School

Background

The multiple indications for central venous catheters (CVCs) include parenteral nutrition,

intravascular depletion, access for vasoactive medications, hemodynamic monitoring,

cardiopulmonary arrest, difficult peripheral intravenous (IV) access and long-term IV access for

medications, such as antibiotics.1,2 While these catheters can be life saving, they are also

associated with significant risks.3

 These risks increase in association with several characteristics,

including patient anatomy (eg, morbid obesity, cachexia, or local scarring from surgery or

radiation treatment), patient setting (eg, patients receiving mechanical ventilation or during

emergencies such as cardiac arrest) and co-morbidities (eg, bullous emphysema or

coagulopathy).3-5

CVCs are placed by clinicians whose training and experience may vary greatly. The

procedure takes place in a variety of hospital settings including intensive care units, emergency

departments, operating rooms, pre- and post-anesthesia care units, hemodialysis units, cardiac

catheterization units and other inpatient settings. Outpatient placement of CVCs has also become

commonplace, occurring in hemodialysis centers and oncology centers providing outpatient

chemotherapy.

Percutaneous insertions of CVCs are usually performed by “blind” techniques that rely

on anatomic landmarks – ie, palpable or visible structures with known relationships to the

desired vein. For example, the infraclavicular approach to the subclavian vein requires correct

localization of the clavicle reference site, suprasternal notch and sternocleidomastoid-clavicular

triangle landmarks, proper positioning of the patient and operator and correct venipuncture point

depth, direction and insertion angle. Analogously, the various approaches to the internal jugular

vein require thorough knowledge of this vein’s course in relation to the sternocleidomastoid

muscle and carotid artery.1

Newer technologies, such as portable ultrasound (US) devices, provide bedside imaging

of the central veins during catheter placement. The advantages associated with US guided CVC

placement include detection of anatomic variations and exact vessel location, avoidance of

central veins with pre-existing thrombosis that may prevent successful CVC placement, and

guidance of both guidewire and catheter placement after initial needle insertion. This review

assesses the impact of real-time ultrasound guidance on improving the safety of CVC insertions.

Practice Description

Real-time ultrasound guidance of CVC insertion provides the operator with visualization

of the desired vein and the surrounding anatomic structures prior to and during insertion of the

needle, guidewire and catheter. Previous studies of US location of vessels followed by

subsequent catheter placement with landmark techniques found no advantages over standard

landmark techniques.3

 Real-time US guidance, on the other hand, appears to improve the success

rate and decrease the complication rate associated with CVC placement.

Two types of real-time ultrasound guidance are described. The Doppler US guidance

method include audio-guided Doppler,6

 fingertip pulsed Doppler7 and probe-in-the-needle
246

technology.6,8-10 The non-Doppler US guidance methods (subsequently referred to as US

guidance) includes US with needle guidance11,12 or without needle guidance.13-15

Prevalence and Severity of the Target Safety Problem

The annual number of all CVCs insertions in the United States is not known, but is

estimated at “several million” for subclavian-vein catheters.3

 When aggregated with the various

types of catheters placed into the central venous circulation and the increasing utilization of

CVCs among routine surgical patients, critically ill patients (in both emergency departments and

intensive care units), and for the management of many patients undergoing hemodialysis or

chemotherapy, the total number of CVC placements may be many times greater than estimates

for subclavian CVCs alone.3

Unsuccessful insertion of CVCs may occur in up to 20% of cases.3-5 The hazards

associated with attempted CVC insertion (whether successful or not) include arterial puncture,

hematoma, pneumothorax, hemothorax, chylothorax, brachial plexus injury, arrhythmias, air

embolus, catheter malposition and catheter knotting.3-5 Other complications associated with

CVCs, such as infection, thrombosis, arterial-venous fistula and vascular or cardiac erosion, are

not usually associated with needle insertion but occur after catheter placement.3-5

The frequency of complications associated with CVC placement is quite variable, largely

due to differences among selected venous insertion sites, the degree of prior operator experience

and the presence of previously described risk factors. In general, the rate of major CVC

complications (eg, pneumothorax or vessel laceration requiring repair) and minor complications

(eg, arterial puncture without significant hemorrhage, transient catheter malposition) is between

0.5 and 10%.3-5

In addition to complications, several quality-of-care issues are associated with problems

in CVC insertion. For example, a CVC insertion that requires multiple attempts may engender

considerable patient anxiety and discomfort. More importantly, a prolonged insertion process

may delay the infusion of life-saving fluids or medications during an emergency.

Opportunities for Impact

The majority of CVC insertions are placed using the landmark method. As set forth

above, the number of catheters placed annually and the proportion currently inserted without US

guidance is not known. Also unknown is the proportion of catheters placed in those patients who

may benefit most from the US technique—those with multiple risk factors, those in high risk

settings such as the intensive care unit, or those undergoing catheter placement by inexperienced

operators.

There are a variety of catheters that require access to the central veins. These include

single and multi-lumen CVCs, tunneled and non-tunneled catheters, and larger, more rigid

catheter introducers that permit passage of thinner, more flexible devices (eg, pulmonary artery

catheters, diagnostic cardiac catheters and temporary transvenous pacemakers). All centrallyplaced catheters require an initial needle insertion into the vein, followed by a guidewire to

permit passage of the catheter.

Study Designs

One meta-analysis and 10 original studies were analyzed. Among the 10 original studies,

9 were randomized control studies and 1 study was a quasi-randomized control trial (see Table

21.1).11 The meta-analysis16 includes 6 references cited in this chapter.6,8,10,12-14 Four articles

cited in this chapter were not cited in the 1996 meta-analysis, including 3 that were published
247

after 19969,15,17 and one that included a quasi-randomized design.17 Two studies included in the

meta-analysis were not included in this chapter because they were from non-English language

journals.7,18

All of the studies analyzed for this chapter were prospective, non-blinded and

randomized, with the exception of a quasi-randomized design involving alternate week

allocation of patients to receive the intervention.11 Randomization was at the patient (rather than

physician) level in all studies.

The 10 original studies include 5 using an ultrasound guidance technique without

Doppler and 5 using the Doppler US technique. Sites of catheterization included the internal

jugular (IJ) veins in 6 studies, the subclavian (SC) veins in 3 studies and the femoral veins in 1

study. The study populations are diverse and include intensive care unit patients, surgical

patients both preoperatively and intraoperatively, cardiac patients in both the catheterization and

coronary care units, emergency department patients in cardiopulmonary arrest and oncology

center outpatients.

Examples of studies excluded from analysis are studies lacking comparison control

groups,19-27 studies of US use but without real-time guidance,3,28 and simulations of CVC

placement rather than completed procedures.29

Study Outcomes

Studies included for review reported a combination of clinical outcomes. These outcomes

include Level 1 complications that resulted in increased patient morbidity (eg, pneumothorax)

and Level 2 complications that represent potential adverse events (eg, unwanted arterial puncture

without sequelae). Most studies also reported the number of venipuncture attempts to achieve

successful CVC placement as well as the time required to complete successful CVC insertions.

These are considered Level 2 outcomes because increased venipuncture attempts are associated

with increased complication rates.4

Evidence for Effectiveness of the Practice

The 1996 meta-analysis16 estimated that real-time US guidance for CVC insertion is

associated with a significant reduction in placement failures as compared with the usual

landmark techniques (relative risk 0.32, 95% CI: 0.18-0.55). In addition, this review estimated

that US guidance results in decreased complications during attempted CVC placements (relative

risk 0.22, 95% CI: 0.10-0.45), corresponding to a relative risk reduction of 78%.16 The mean

number of attempted venipunctures till successful CVC insertion was significantly reduced with

real-time US guidance (relative risk 0.60, 95% CI: 0.45-0.79), corresponding to a relative risk

reduction of 40%.16

Two of the 3 studies reviewed for this chapter and not included in the meta-analysis

(because they were published subsequently) deserve mention because of contrary findings. Both

1998 studies9,17 included operators with significant prior experience placing CVCs by the usual

landmark method. The overall failure rate for both landmark and US guidance techniques was

very low in one study.17 The other study found statistically insignificant negative results

associated with US guidance, owing to a high failure rate during the initial learning period for

the newly-introduced US guidance technique, and a very low (1.3%) overall complication rate

for CVC placement.9

With the exception of femoral venous catheterization during cardiopulmonary

resuscitation,15 the studies reviewed for this chapter did not find reductions in insertion time

when using real-time US guidance. With 2 exceptions,910 the cited studies reached statistical
248

significance for at least one of the 3 outcome measures (morbidity, potential adverse events, and

number of venipuncture attempts). The most favorable outcomes associated with real-time US

guidance were found in studies of inexperienced operators.6,12,13

Potential for Harm

The additional equipment and manipulation associated with real-time US guidance for

CVC insertion may increase the rate of catheter-related infections, but published studies have not

included these complications. In emergency settings, the increased length of time required to

place CVCs under US guidance (usually an additional 30 seconds to several minutes) may result

in unacceptable delays. Potential harmful consequences resulting from real-time US guidance for

CVC placement relate to changes in training and subsequent dependence on this technology.

Supporters of this technology argue that increased competence and anatomic knowledge gained

with US guidance will enhance performance of customary, unaided CVC placement. It is unclear

if trainees who have performed CVC placement only with US assistance will have different

complication rates when placing CVCs in practice settings without US equipment. Therefore, for

certification of qualification, trainees may need to demonstrate competence with both US and

non-US guided CVC placement.

Costs and Implementation

The major impediments to the widespread implementation of US guidance for CVC

insertion are the purchase costs of the US machines. A typical machine costs $11,000-16,000

(including the probes), with a single machine able to serve most critical care units. Depending on

the layout of units placing CVCs, an average 400-bed hospital would require 1-3 machines for

use outside of the operating room. (Departments of Anesthesia may require only one or two

machines, as experienced anesthesiologists can continue to place most CVCs without US

guidance). Hospitals in which nurses place peripherally inserted central catheter (PICC) lines

using US guidance typically facilitate this function with a single machine, which could be dually

used for CVCs depending on workflow and volume. In one study, the price of the Doppler-Smart

needles (which are not required for non-Doppler US guidance) was $40-70 as compared with $3-

5 for the standard needles.9

 The cost of training new operators (including those whose only prior

experience is with the landmark technique) requires further evaluation.
249

Comment

Real-time US guidance for CVC insertion, with or without Doppler assistance, improves

catheter insertion success rates, reduces the number of venipuncture attempts prior to successful

placement, and reduces the number of complications associated with catheter insertion.

However, these benefits may not accrue until after the initial learning period for operators

already experienced in the landmark techniques.9

There are no studies comparing the impact of CVC insertion with US guidance on overall

patient outcomes (eg, mortality, length of stay). In addition, many of the complications

associated with CVC insertion are minor or easily treated. The reduction in venipuncture

attempts is likely associated with reductions in the pain and discomfort associated with CVC

placement, though this has not been measured.

The greatest benefit of US guidance may apply to the novice or inexperienced operator

and for all operators in high-risk situations. Patients with one or more risk factors, (eg, critically

ill patients on positive pressure ventilation with generalized edema and coagulopathy), may reap

the greatest benefit. CVC insertion training incorporating real-time ultrasound guided techniques

may provide additional valuable learning benefits for new operators. This knowledge may

improve the success rate of insertion of CVCs without US guidance. Simulation training has

demonstrated improved identification of the desired veins with US as compared to landmark

techniques.29

Finally, it should be noted that in addition to real-time US guidance, other approaches

may reduce the risks associated with CVC insertion. PICC lines are gaining widespread

acceptance and may be an acceptable substitute for CVCs for certain indications (eg, long-term

IV access or parenteral nutrition).30,31 US guidance has also been demonstrated to improve the

insertion of PICCs.32-34 Increases in the use of PICCs may help justify the purchase of ultrasound

machines by individual hospitals.

For patients requiring replacement of existing CVCs, guidewire exchanges offer a way of

inserting new catheters without new venipuncture attempts. A systematic review has found that

guidewire exchanges are associated with fewer mechanical complications than new-site

replacement, but may be associated with greater risks for catheter-related infections (Chapter

16).35

Alternative methods for teaching CVC insertion skills to novices (eg, first-year resident

physicians and medical students) have successfully employed multidisciplinary approaches

including cadaver demonstrations.36 Future methods for teaching CVC insertion may employ

computerized technologies for simulations (see also Chapter 45). Haptic, or touch-related

techniques use virtual reality models to create immersive simulated environments that recreate

the sensation of performing a procedure.37,38 Through the use of this and other new technologies,

novice operators may gain experience and confidence prior to clinical CVC insertion attempts

and further improve patient safety.
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Table 21.1. Ultrasound and Doppler ultrasound guidance of central vein catheters*

Study Setting and Relative Risk Reduction (%)†

Population

Year

Published

Intervention Study

Design,

Outcomes Failed

Catheter

Insertion

Mean

Insertion

Attempts

Required§

Complications

Ultrasound

Tertiary care, teaching

hospital ICU13

1990 US guidance for IJ CVC insertion

without needle guide; concurrent

feedback from an US technician

Level 1

Level 2

100NS 44 NA

Tertiary care, teaching

hospital, CT surgical

patients14

1991 US guidance (7.5 and 5.0 MHz

transducers) for IJ CVC insertion

without needle guide

Level 1

Level 2

100 44 83NS

Tertiary care, teaching

hospital, cardiac

patients11

1993 US guidance (7.5 MHz

transducer) of IJ cannulation for

cardiac catheterization and CVC

insertion, with needle guide

Level 1

Level 2

100 48 80

Urban, teaching

hospital ICU12

1995 US guidance (7.5 MHz

transducer) for SC CVC insertion

with needle guide

Level 1

Level 2

86 48 90

Urban, teaching

hospital ED, during

CPR15

1997 US guidance (7.5 MHz

transducer) for femoral CVC

insertion without needle guide

Level 1

Level 2

71 54 100

Doppler Ultrasound

Tertiary care, teaching

hospital, CT/ vascular

surgery patients8

1994 Doppler US guidance of IJ CVC

insertion with probe in the needle

Level 1

Level 2

0 52 0

British hospital,

cardiac surgery and

ICU patients10

1994 Doppler US guidance of IJ CVC

insertion with probe in the needle

Level 1

Level 2

-50NS 17NS 0

Tertiary care, teaching

hospital ICU and OR;

high-risk patients6

1995 Audio-guided Doppler US

guidance for IJ CVC insertion

with probe in the needle

Level 1

Level 2

63 18NS 88

French teaching

hospital ICU; low-risk

patients17

1998 Pulsed Doppler US guidance for

SC CVC insertion without needle

guide

Level 1

Level 2

-32§ 0 67

Tertiary care,

outpatient oncology

center9

1998 Doppler US guidance for SC

CVC insertion with probe in the

needle

Level 1

Level 2

-46§ NA -53NS

* CPR indicates cardiopulmonary resuscitation; CT, cardiothoracic; ED, emergency department; ICU, intensive care

unit; IJ, internaljugular vein; NA, not available; NS, not statistically significant; OR, operating room; RCT,

randomized controlled trial; SC, subclavian vein; and US, ultrasound guidance.

† The percentage relative risk reduction reflects the risks associated with CVC placement and the percentage change

resulting from US guidance. Negative values indicate an increase in risks associated with US guidance.

§ Relative risk reduction of the insertion attempts to success reflects the relative reduction in the mean number of needle

insertions attempted per patient until successful CVC placement resulting from US guidance.
251

References

1. Civetta JM, Taylor RW, Kirby RR. Critical Care. 3rd ed. Philadelphia: Lippincott-Raven

Publishers, 1997.

2. Shoemaker W, Ayres S, Grenvik A, Holbrook P. Textbook of Critical Care. 4 ed.

Philadelphia: WB Saunders, 2000.

3. Mansfield PF, Hohn DC, Fornage BD, Gregurich MA, Ota DM. Complications and failures

of subclavian-vein catheterization. N Engl J Med. 1994;331:1735-1738.

4. Sznajder JI, Zveibil FR, Bitterman H, Weiner P, Bursztein S. Central vein catheterization.

Failure and complication rates by three percutaneous approaches. Arch Intern Med.

1986;146:259-261.

5. Bernard RW, Stahl WM. Subclavian vein catheterizations: a prospective study. I. Noninfectious complications. Ann Surg. 1971;173:184-190.

6. Gilbert TB, Seneff MG, Becker RB. Facilitation of internal jugular venous cannulation

using an audio-guided Doppler ultrasound vascular access device: results from a

prospective, dual-center, randomized, crossover clinical study. Crit Care Med. 1995;23:60-

65.

7. Branger B, Zabadani B, Vecina F, Juan JM, Dauzat M. Continuous guidance for venous

punctures using a new pulsed Doppler probe: efficiency, safety. Nephrologie. 1994;15:137-

140.

8. Gratz I, Afshar M, Kidwell P, Weiman DS, Shariff HM. Doppler-guided cannulation of the

internal jugular vein: a prospective, randomized trial. J Clin Monit. 1994;10:185-188.

9. Bold RJ, Winchester DJ, Madary AR, Gregurich MA, Mansfield PF. Prospective,

randomized trial of Doppler-assisted subclavian vein catheterization. Arch Surg.

1998;133:1089-1093.

10. Vucevic M, Tehan B, Gamlin F, Berridge JC, Boylan M. The SMART needle. A new

Doppler ultrasound-guided vascular access needle. Anaesthesia. 1994;49:889-891.

11. Denys BG, Uretsky BF, Reddy PS. Ultrasound-assisted cannulation of the internal jugular

vein. A prospective comparison to the external landmark-guided technique. Circulation.

1993;87:1557-1562.

12. Gualtieri E, Deppe SA, Sipperly ME, Thompson DR. Subclavian venous catheterization:

greater success rate for less experienced operators using ultrasound guidance. Crit Care

Med. 1995;23:692-697.

13. Mallory DL, McGee WT, Shawker TH, Brenner M, Bailey KR, Evans RG, et al. 

Ultrasound guidance improves the success rate of internal jugular vein cannulation. A

prospective, randomized trial. Chest. 1990;98:157-160.

14. Troianos CA, Jobes DR, Ellison N. Ultrasound-guided cannulation of the internal jugular

vein. A prospective, randomized study. Anesth Analg. 1991;72:823-826.

15. Hilty WM, Hudson PA, Levitt MA, Hall JB. Real-time ultrasound-guided femoral vein

catheterization during cardiopulmonary resuscitation. Ann Emerg Med. 1997;29:331-336.

16. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement of

central venous catheters: a meta-analysis of the literature. Crit Care Med. 1996;24:2053-

2058.

17. Lefrant JY, Cuvillon P, Benezet JF, Dauzat M, Peray P, Saissi G, et al. Pulsed Doppler

ultrasonography guidance for catheterization of the subclavian vein: a randomized study.

Anesthesiology. 1998;88:1195-1201.
252

18. Scherhag A, Klein A, Jantzen J. Cannulation of the internal jugular vein using 2 ultraosnic

techniques:A comparitive controlled study. Anaesthesist 1989;38:633-638.

19. Fry WR, Clagett GC, O'Rourke PT. Ultrasound-guided central venous access. Arch Surg.

1999;134:738-740.

20. Gordon AC, Saliken JC, Johns D, Owen R, Gray RR. US-guided puncture of the internal

jugular vein: complications and anatomic considerations. J Vasc Interv Radiol. 1998;9:333-

338.

21. Sato S, Ueno E, Toyooka H. Central venous access via the distal femoral vein using

ultrasound guidance. Anesthesiology. 1998;88:838-839.

22. Docktor B, So CB, Saliken JC, Gray RR. Ultrasound monitoring in cannulation of the

internal jugular vein: anatomic and technical considerations. Can Assoc Radiol J.

1996;47:195-201.

23. Hatfield A, Bodenham A. Portable ultrasound for difficult central venous access. Br J

Anaesth. 1999;82:822-826.

24. Gallieni M, Cozzolino M. Uncomplicated central vein catheterization of high risk patients

with real time ultrasound guidance. Int J Artif Organs. 1995;18:117-121.

25. Geddes CC, Walbaum D, Fox JG, Mactier RA. Insertion of internal jugular temporary

hemodialysis cannulae by direct ultrasound guidance—a prospective comparison of

experienced and inexperienced operators. Clin Nephrol. 1998;50:320-325.

26. Cavatorta F, Zollo A, Campisi S, Trabassi E, De Lucia E, Galli S, et al. Internal jugular

vein catheterization under echographic guidance. Int J Artif Organs. 1993;16:820-822.

27. Hrics P, Wilber S, Blanda MP, Gallo U. Ultrasound-assisted internal jugular vein

catheterization in the ED. Am J Emerg Med. 1998;16:401-403.

28. Hayashi H, Tsuzuku M, Amano M. Simplified echo-guided internal jugular vein puncture:

a comparison to the landmark-guided technique. Anesth.Analg. 1998;86:SCA89

29. Hirvela E, Parsa C, Aalmi O, Kelly E, Goldstein L. Skills and risk assessment of central

line placement using bedside simulation with 3-dimensional ultrasound guidance system.

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30. Lam S, Scannell R, Roessler D, Smith MA. Peripherally inserted central catheters in an

acute-care hospital. Arch Intern Med. 1994;154:1833-1837.

31. Smith JR, MD, Friedell ML, Cheatham ML, Martin SP, Cohen MJ, et al. Peripherally

Inserted Central Catheters Revisited. Am J Surg. 1998;176:208-211.

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Nurs. 2000; 23:29-34.

33. Sofocleous CT, Schur I, Cooper SG, Quintas JC, Brody L, Shelin R. Sonographically

guided placement of peripherally inserted central venous catheters: review of 355

procedures. AJR. 1998;170:1613-1616.

34. Chrisman HBM, Omary RAM, Nemcek AA, Jr, MD, Vogelzang RLM. Peripherally

Inserted Central Catheters: Guidance With Ultrasound Versus Venography in 2650

Patients. J Vasc Interv Radiol. 1998;9:173-174.

35. Cook D, Randolph A, Kernerman P, Cupido C, King D, Soukup C, et al. Central venous

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36. Nip IL, Haruno MM. A systematic approach to teaching insertion of a central venous line.

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37. Hiemenz L, Stredney D, Schmalbrock P. Development of the force-feedback model for an

epidural needle insertion simulator. Stud Health Technol Inform. 1998;50:272-277.
253

38. Kaufmann C, Rhee P, Burris D. Telepresence surgery system enhances medical student

surgery training. Stud Health Technol Inform. 1999;62:174-178.
254
255

Chapter 22. The Retained Surgical Sponge

Verna C. Gibbs, MD

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Background

Although less likely to garner public notoriety, errors relating to the failure to remove

surgical instruments at the end of a procedure, (ie, needles, knife blades, electrosurgical adapters

and safety pins) or sponges (known as gossypiboma; gossypium: Latin, cotton; boma: Swahili,

place of concealment) are no less egregious than the better known mishaps such as “wrong-site

surgery” (see Subchapter 43.2).

Retained materials may cause an acute foreign body reaction with local or systemic signs

that prompt investigation and reoperation. Alternatively, a fibrinous response may be elicited,

and the retained instrument or sponge may become apparent some time after the original surgical

procedure either serendipitously, or via fistulization into local structures.1 The medical literature

is scattered with reports of presentations of retained sponges found days, months, or even years

after the original surgery.2-5 While many cases of retained foreign body do not cause harm, some

clearly do. Nevertheless, the Joint Commission on Accreditation for Healthcare Organization’s

(JCAHO) sentinel event policy specifically mentions that “unintentionally retained foreign body

without major permanent loss of function” do not require reporting.6 Although JCAHO’s

decision suggests that it considers these events less egregious than reportable sentinel events (eg,

wrong patient surgery), retained foreign body events are far more common. This chapter reviews

the problem and the scanty literature regarding safety practices to reduce the incidence of

retained sponges and instruments.

Practice Description

Surgeons and operating room teams rely upon the practice of sponge, sharp and

instrument counts as a means to eliminate retained surgical instruments. Counts are also a

method of infection control and inventory control, and a means to prevent injury from

contaminated sharps and instruments. Four separate counts have been recommended7

: the first

when the instruments are set up or the sponges unpackaged, a second before the surgical

procedure begins, a third as closure begins, and the final count performed during subcuticular or

skin closure.

Use of this simple preventative measure is not universal. In fact, the process by which

counts are performed is not standardized and is often modified according to individual hospital

policy. Even when present, counts are frequently omitted or abbreviated in emergency or

transvaginal surgeries, or for vaginal deliveries.8 An adjunctive procedure to the count, used

when the count could delay care and jeopardize patients’ lives or when an incorrect count is

established, is an x-ray examination to detect radiopaque objects.1,7 Since this practice is not

routinely used it will not be discussed here.
256

Prevalence and Severity of the Target Safety Problem

A literature search revealed few data to describe population or even hospital-level

information regarding the prevalence of retained surgical materials. One study from a medical

malpractice insurance company reported 40 cases in a 7-year period,9

 or about 1% of all claims.

Because this estimate is based on malpractice insurance claims, it is sure to be a gross

underestimate of the actual incidence. A recent unstructured review cited “a prevalence ranging

from 1/100 to 1/5000,” and an associated mortality ranging from 11 to 35%, citing non-English

language medical references.1

 Other reports are based on case series or descriptions of unusual

presentations, as described above. Surgeons may not report these events for a variety of reasons,

not the least of which is fear of litigation

Opportunities for Impact

Without accurate prevalence information, the true magnitude of the opportunity for

impact is unclear.

Study Designs and Outcomes

Only one study provided even indirect evidence of the effectiveness of sponge and

instrument counts. Kaiser et al, using a retrospective review of medical malpractice claims data

from a statewide insurer in Massachusetts, reviewed 67 cases where retained sponges or surgical

materials were the primary reason for the claim.9

 This study is a case series without any controls

(Level 4 design, Level 2 outcomes) which reported only the outcome of retained sponges, rather

than the clinical consequences of these errors.

Evidence for Effectiveness of the Practice

The Kaiser et al study reported that 55% of retained sponges were found after abdominal

surgery and 16% after vaginal delivery. In cases with retained sponges, sponge counts had been

falsely correct in 76% of non-vaginal surgeries; in 10% no sponge count had been performed at

all. Falsely correct sponge counts were attributed to team fatigue, difficult operations, sponges

“sticking together,” or a poor counting system. Incorrect sponge counts that were accepted prior

to closure resulted from either surgeons’ dismissing the incorrect count without re-exploring the

wound, or nursing staff allowing an incorrect count to be accepted. Interestingly, in 3 of 29 cases

in which intraoperative x-rays were used to detect radiopaque sponges, the radiograph was

falsely negative.9

Comment

Although literature describing the incidence of iatrogenic foreign bodies is highly limited

in quantity and quality, it is unlikely that these events are as rare as other iatrogenic

complications that have drawn considerable national attention. The existing system of sponge

and instrument counts probably works well, but we have no evidence to describe its actual

failure rate. The little existing evidence suggests that it fails due to human-related factors (ie, the

count is not performed, or is ignored, and that ancillary methods such as x-rays are also fallible.

Although some have advocated CT or ultrasonography as additional methods to reduce rates of

these adverse events, it is possible that other technologies (eg, inventory control devices used in

retail stores and libraries, possibly including bar coding (Subchapter 45.1)) may prove to be

useful adjuncts. However, there are obvious logistical challenges that make such technologies

too impractical at the present time. For now we are left with a paucity of data regarding the
257

prevalence of this error and the effectiveness of preventative measures. Use of anonymous

reporting systems may reduce the fear of litigation associated with iatrogenic foreign bodies, and

may allow for more accurate assessment of the incidence and causes of these events.

References

1. Lauwers PR, Van Hee RH. Intraperitoneal gossypibomas: the need to count sponges.

World J Surg. 2000;24:521-527.

2. Wig JD, Goenka MK, Suri S, Sudhakar PJ, Vaiphei K. Retained surgical sponge: an

unusual cause of intestinal obstruction. J Clin Gastroenterol. 1997;24:57-58.

3. Scott WW, Beall DP, Wheeler PS. The retained intrapericardial sponge: value of the lateral

chest radiograph. AJR Am J Roentgenol. 1998;171:595-597.

4. Sinha SK, Gupta S, Behra A, et al. Retained surgical sponge: an unusual cause of

malabsorption. Trop Gastroenterol. 1999;20:42-44.

5. Burrel M, Capurro S, Arguis P, Vilana R. Sonographic appearance of a retained surgical

sponge in the neck. J Clin Ultrasound. 2000;28:311-313.

6. The Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Alert.

Accreditation Committee Approves Examples Of Voluntarily Reportable Sentinel Events.

May 11, 1998. Available at: http://www.jcaho.org/edu_pub/sealert/sea4.html. Accessed

June 23, 2001.

7. Recommended practices for sponge, sharp, and instrument counts. AORN Recommended

Practices Committee. Association of periOperative Registered Nurses. AORN J.

1999;70:1083-9.

8. Horty J. Nurses, surgeon not negligent in retained instrument suit. Kissinger v Turner. OR

Manager. 1995;11:26, 30.

9. Kaiser CW, Friedman S, Spurling KP, Slowick T, Kaiser HA. The retained surgical

sponge. Ann Surg. 1996;224:79-84.
258
259

Chapter 23. Pre-Anesthesia Checklists To Improve Patient Safety

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Harvey J. Murff, MD

Harvard Medical School

Salim D. Islam, MD

University of California, San Francisco School of Medicine

Background

No matter how rote the task or how vigilant the anesthesiologist, “slips” and other errors

represent expected aspects of human performance.1

 Evaluation and subsequent improvement of

standard checkout procedures promises to increase patient safety in the perioperative period by

removing more of the “human factors” so often implicated in anesthesia adverse events.2 The use

of pre-flight checklists has been considered a key method in improving airline safety, largely due

to the regular systematizing of complex procedures, and improvement of team dynamics through

authority-neutral tasks. A checklist system has been proposed as part of routine pre-anesthesia

care, with the American Society of Anesthesiologists and the US Food and Drug Administration

(FDA) issuing general guidelines supporting checklists in 1986.3

 Subsequently, anesthesia

professional societies in Great Britain and Europe adopted similar standards.4

Practice Description

In 1987, the FDA published the “Anesthesia Apparatus Checkout Recommendations” in

the Federal Register (February, 1987). This “checkout list” provides practitioners with a

standardized approach to checking anesthetic equipment prior to its use in order to ensure that

the delivery system is correctly connected, adjusted, and functional. The original checklist

included 24 specific processes to be performed as an initial checkout at the beginning of each

day; 11 are performed between cases and after initial equipment evaluation.5

 Many clinicians

regarded these protocols as too long and complex for routine use. Parties involved in revising the

recommendations agreed that the average clinician should be able to check an anesthesia

machine in 5 minutes or less (not possible with the 1987 recommendations). The revised

checklist included only 14 major processes, 9 of which can be omitted or substantially

abbreviated when the anesthesia provider uses the same equipment in successive cases.6

 The

revised recommendations are available online.7

Prevalence and Severity of the Target Safety Problem

The earliest observational studies of mishaps within anesthesia found that equipment

failure was the cause of 14% of anesthesia critical incidents.8

 Subsequent studies reduced this

estimate considerably. Although equipment failure is now implicated in only 4% of anesthesia

adverse events, 22% are related to failing to check equipment adequately.2

 Equipment failures

can result in delivery of hypoxic gas mixtures or excessive doses of inhalational agent, or

hypoventilation due to ventilator failure. These situations can be catastrophic if unrecognized,

and even if recognized may result in significant morbidity (eg, delayed extubation, stroke, or

myocardial infarction).2,9
260

Opportunities for Impact

The FDA checkout list is considered a template which local users are “encouraged to

modify to accommodate differences in equipment and variations in local clinical practice.”

Estimating the frequency with which it or other checklists are used (in modified or unmodified

forms) in anesthesia practice would be speculative,5

 but a survey of 4 states suggests that usage

is minimal.3

 There are 41.5 million inpatient procedures each year requiring anesthesia in the

US. Probably about half of these involve general anesthesia. Therefore, although the frequency

of equipment failure is low, any improvement in safety from anesthesia preoperative checklists

could have substantial impact.

Study Designs

Using a structured MEDLINE search, we identified 15 articles that discussed anesthesia

checklists. Of these, only 2 studies came close to meeting our inclusion criteria (Chapter 3).3,10

Because no other studies could be found, we abstracted these studies and review them here

(Table 23.1).

The first investigation evaluated the ability of participating providers to detect

standardized equipment faults using their own checking methods compared with the FDA

checkout list.3 Although the study involved a prospective design, it does not fit neatly into our

classification system because the participants (anesthesiology residents and practitioners) served

as their own controls. The second study10 involved the revised FDA checkout list, and its design

was modeled on the previous study.

Study Outcomes

The first study’s outcome of interest was the detection of 4 standardized equipment faults

created by the investigators (Level 2).3

 The second study used similarly designed outcomes

(simulated equipment faults), but defined detection of at least 50% of these faults as the primary

outcome (Level 2).10 Neither study directly connected the use of pre-anesthesia checklists to

patient outcomes, although inadequate preanesthesia equipment checks have been implicated in

adverse events related to equipment failures, as discussed above.2

Evidence for Effectiveness of the Practice

March et al3

 found that the FDA checklist was more likely to detect faults with the

nitrous oxide system (65% vs. 43%, p<0.001), but that the FDA checklist was no better than

individual practitioners' checklists in detecting the 7 other pre-set faults. No method detected

100% of faults, but those physicians with more clinical practice and those with better knowledge

of the FDA checklist were more effective at detecting equipment faults. In the study of the

revised FDA checklist,9

 approximately half of the participants failed to detect at least half of the

faults using both their own methods and the FDA checkout list (no statistically significant

difference).

Both of these studies contain important methodologic flaws. The participants knew they

were involved in a study assessing their ability to detect machine faults, and so undoubtedly

approached this task with increased sensitivity. Moreover, the participants’ own methods may

have been quite similar to the use of the FDA checklist. Both of these problems bias these

studies against finding a difference between checklist and controls. Importantly though, all

methods performed poorly in both studies. Thus, even if the FDA checkout list is in fact superior
261

to anesthesia providers’ own methods, the observed utility of this practice still is likely to be

quite low.

Potential for Harm

We were unable to find literature that implicated checklists as causes of adverse events.

There exists a theoretical possibility of delays due to complex checklists, but these have not been

borne out in any published studies. There has also been concern raised about compulsory

checklist procedures as an unnecessary duplication of work already performed by operating

room technical personnel.

Costs and Implementation

The FDA checklist, or local variants thereof, is widely implemented and inexpensive.

Although several authors have mentioned that checkout processes are not used in 100% of cases,

this does not seem to reflect problems with checklists themselves.4,12,13 The work of March and

Crowley3

 suggests that checklists training may be critically important. However, the most

important barrier to implementation is the heterogeneity of anesthesia delivery devices

themselves, which makes creation of a single, effective, broadly generalizable checklist difficult

if not impossible.

Comment

Given its face validity and the theoretical connection between anesthesia checklists and

those used so effectively in aviation, preanesthesia checklists represent plausible safety tools.

However, the reliability of modern anesthesia machines has reduced the frequency of mechanical

failure to such a degree that adverse outcomes due to anesthesia machine failure are exceedingly

rare. The checklists examined in the cited studies only examine the integrity of the anesthesia

machine and ventilatory monitors, not cardiovascular monitors, airway equipment, intravenous

apparatus, infusion pumps, or medications. Standardized checklists for these other critical

components of anesthesia care do not exist in the literature. This may explain the paucity of

literature exploring the use of checklists and their real effects on patient outcomes. Furthermore,

the inability of anesthesiologists to detect preset faults in the cited studies may simply reflect the

infrequency with which such faults are encountered in modern anesthesia practice.

The face validity of checklists and the difficulty of “probing” their value in clinical

studies make additional “proof of concept” studies unlikely. Although future investigations could

not ethically study the anesthesia machine checklist per se, they could seek to determine more

effective methods for its implementation, or could develop additional checklists with a broader

scope. The little evidence we have been able to uncover suggests that, like the use of voluntary

guidelines elsewhere in medicine (Chapter 51), checklists are not used uniformly. This may

result from a sense that these checks are low-yield, redundant, onerous, or all of the above.

The need for effective checkout procedures is likely to grow as the complexity of

anesthesia equipment increases. This will increase the need to make checklists more sensitive

and specific in detecting faults, while improving usability. These worthy goals may then serve as

templates for other technologically dependent medical specialties, such as cardiac

electrophysiology, and interventional radiology.
262

Table 23.1. Evaluations of the FDA “checkout list” for preoperative anesthesia equipment

assessment

Study Study Design,

Outcomes

Results

March, 19913: Exposure of a total of

188 anesthesiology residents and

practitioners from multiple sites to a

“mobile anesthesia study center” with 2

anesthesia machines pre-set to one of

two different “fault sets.” Each of these

sets included 4 independent machine

faults. Practitioners were instructed to

use their own checkout methods to

assess a machine with one of the “fault

sets.” After completion of this

assessment, the machine was adjusted to

display the other fault set, and the

participant invited to use the FDA

checkout list in the second assessment.

Mixture of

Levels 2 & 3,

Level 2

Participants detected an average of

only 1 in 4 machine faults. A

statistically significant

improvement in the fault detection

rate with use of the FDA checkout

compared with the participants’

individual methods was observed

for only 1 of the 4 fault types

(involving the oxygen/nitrous

oxide ratio).

Manley, 19969: Similar study to above,

but involving only 22 participants (a

mixture of anesthesiologist, nurse

anesthetists, and senior nurse anesthetist

students) from only one site.

As above For both of the fault sets,

approximately half of the

participants detected fewer than

50% of the 4 target faults using

their own individual methods. The

detection rates using the revised

FDA checkout list did not differ

significantly (p=0.48) from these

results.
263

References

1. Reason JT. Human Error. New York: Cambridge Univ Press; 1990.

2. Cooper JB, Newbower RS, Kitz RJ. An analysis of major errors and equipment failures in

anesthesia management: considerations for prevention and detection. Anesthesiology.

1984;60:34-42.

3. March MG, Crowley JJ. An evaluation of anesthesiologists' present checkout methods and

the validity of the FDA checklist. Anesthesiology. 1991;75:724-729.

4. Charlton JE. Checklists and patient safety. Anaesthesia. 1990;45:425-426.

5. Walker JS, Wilson M. Clinical risk management in anaesthesia. Qual Health Care.

1995;4:115-121.

6. Anesthesia Apparatus Checkout Recommendations, 1993. Fed Regist. 1994;59:35373-74.

7. U.S. Food and Drug Adminstration. Anesthesia apparatus checkout recommendations.

Available at: http://www.fda.gov/cdrh/humfac/anesckot.pdf. Accessed June 10, 2001.

8. Cooper JB, Newbower RS, Long CD, McPeek B. Preventable anesthesia mishaps: a study

of human factors. Anesthesiology. 1978;49:399-406.

9. Spooner RB, Kirby RR. Equipment-related anesthetic incidents. Int Anesthesiol Clin.

1984;22:133-147.

10. Manley R, Cuddeford JD. An assessment of the effectiveness of the revised FDA checklist.

AANA J. 1996;64:277-282.

11. Degani A, Wiener EL. Cockpit checklists - concepts, design, and use. Human Factors.

1993;35:345-359.

12. Cooper JB, Cullen DJ, Eichhorn JH, Philip JH, Holzman RS. Administrative guidelines for

response to an adverse anesthesia event. The Risk Management Committee of the Harvard

Medical School's Department of Anaesthesia. J Clin Anesth. 1993;5:79-84.

13. Currie M. A prospective survey of anaesthetic critical events in a teaching hospital.

Anaesth Intensive Care. 1989;17:403-411.
264
265

Chapter 24. The Impact Of Intraoperative Monitoring On Patient Safety

Salim D. Islam, MD

Andrew D. Auerbach, MD, MPH

University of California, San Francisco School of Medicine

Background

Until the 1960s, intraoperative monitoring consisted of a blood pressure cuff,

electrocardiogram (ECG), stethoscope, and the vigilance of the anesthesiologist. Over the next 2

decades, the array of available monitors burgeoned, and clinical practice varied widely. In 1986,

in an effort to improve patient safety, standards for intraoperative monitoring were developed

and implemented by the American Society of Anesthesiologists (ASA).1

 They have been almost

universally adopted by anesthesia providers in the United States and now form the standard of

care in this country. The ASA standards are summarized in Figure 24.1.

Concurrently with the implementation of better monitoring, anesthesia-related mortality

has fallen sharply. Proponents of monitoring claim that better monitoring is the reason for

improvement in patient safety.2-4 Others have claimed that advances in knowledge and training

combined with the development of safer medications have had as much impact on patient safety

as the adoption of monitoring standards.5,6 In this chapter, we evaluate the evidence linking

intraoperative monitoring to patient safety.

Practice Description

Intraoperative monitoring involves the use of mechanical devices to record and display

physiologic parameters such as heart rate, blood pressure, oxygen saturation, and temperature.

Standard routine monitoring is noninvasive, employing blood pressure cuff, ECG, and pulse

oximetry.

Invasive monitors such as arterial and central venous catheters and transesophageal

echocardiography may provide more detailed and timely physiologic information, but also pose

an increased risk for iatrogenic complications. In practice these monitors are used selectively,

and are not reviewed here.

Prevalence and Severity of the Target Safety Problem

Death due to anesthesia has become rare. In one large Canadian study involving 27,184

inpatients who underwent anesthesia, physician review of 115 randomly selected “major events”

classified less than 20% as having any anesthetic involvement, with no deaths even partially

attributed to anesthesia.7

 In the United States, the mortality due to general anesthesia has been

estimated at approximately 5000 deaths per year (in the 1970s),8

 with approximately half that

number estimated in the 1980s.9

 Thus, general anesthesia represents the one aspect of health care

where the risk of death is low enough to rival the safety record achieved in other high-risk

industries such as aviation.10

By contrast, morbid events (complications) related to anesthetic care are likely more

prevalent and difficult to classify as preventable or unavoidable. Because certain aspects of

monitoring may reduce the incidence of morbid events unrelated to anesthesia, assessing the

impact of monitoring practices solely on anesthetic outcomes may be inappropriate. For

example, detection of a consistent decrease in intraoperative blood pressure may signal

unrecognized bleeding, allowing the anesthesiologist to alert the surgeon to this possibility and

prompting appropriate management. While intraoperative hemorrhage does not represent an
266

anesthetic complication, intraoperative blood pressure monitoring can clearly contribute to the

overall safety of the surgical patient. Thus, the scope of intraoperative morbidity targeted by

anesthetic monitoring practices is much broader than the set of possible complications

attributable solely to the administration of anesthesia.7-9

Opportunities for Impact

In the United States, there are no mandatory regulations for monitoring practices.

However, virtually all anesthesiologists abide by the monitoring standards set forth by the 1986

ASA standards, last modified in 1998 (Figure 24.1). Although these standards were implemented

with only speculative evidence of their benefit,4

 few clinicians doubt their merit.

Study Designs

Using a structured MEDLINE search, we identified articles presenting data related to the

impact of perioperative monitoring. Many of these studies11-17 involved Level 4 designs (eg,

observational studies without a control group). For instance, several of the articles11-13,15 reported

data from the Australian Incident Monitoring Study and involved analysis of a case series of

2000 incident reports without accompanying controls. Other studies only indirectly pertained to

intraoperative monitoring. One study surveyed anesthesiologists regarding their views on the

appropriate alarm settings for intraoperative blood pressure monitoring.18 Another focused on the

personnel performing intraoperative monitoring—physician anesthesiologists versus certified

nurse anesthetists.19 We chose not to purse this contentious and intensely political comparison,

as few studies have compared the outcomes achieved by these two groups. Moreover, our

reviewer team did not include a nurse anesthetist, making any conclusions drawn more

susceptible to bias. Of the 3 remaining studies, one involved a non-randomized clinical trial

(Level 2), but a Level 3 outcome.20

The remaining 2 studies met our inclusion criteria (Chapter 3). One was a retrospective

analysis of anesthesia accidents before and after the implementation of monitoring standards

(Level 3),2

 and the other used a prospective, randomized, controlled trial design (Level 1) to

assess the impact of pulse oximetry on postoperative complications (Level 1 outcome).21

Study Outcomes

The 2 studies2,21 meeting the methodologic inclusion criterion reported morbidity and

mortality (Level 1) attributable to anesthesia, ie, a major complication or death occurring in the

immediate postoperative period not obviously explained by the patient’s underlying condition or

the operation itself.

Evidence for Effectiveness of the Practice

Through a review of cases reported to a liability insurer, Eichhorn identified 11 major

intraoperative accidents solely attributable to anesthesia among over 1,000,000 cases performed

at the nine Harvard hospitals from 1976-1988.2

 Eight of these accidents were judged to be

preventable as they were caused by failure to ventilate or to deliver adequate oxygen to the

patient. Only one of these accidents occurred after the adoption of monitoring standards in mid1985, supporting the safety benefit of intraoperative monitoring standards, although the

difference in accident frequency was not statistically significant.

In a multicenter, randomized, controlled trial of 20,802 surgical patients, Moller et al21

studied the impact of perioperative pulse oximetry on patient outcome. Despite the large sample,

the authors were unable to show a difference in in-hospital mortality or postoperative
267

complications. During anesthesia and in the post-anesthesia care unit (PACU), more episodes of

hypoxemia and myocardial ischemia were detected in patients monitored with pulse oximetry.21

Potential for Harm

Routine noninvasive monitoring carries minimal (although not zero) additional risk for

iatrogenic complications from the devices themselves. Current standard of practice requires that

they be used in all cases of general or regional anesthesia. However the number of monitors and

their concomitant alarms raises the possibility of additional harm. A study of monitor alarms in

the intensive care unit (ICU) suggested that monitor alarms might actually reduce quality of care

because of their high frequency and low specificity. In this study, an alarm occurred every 37

minutes, and in the majority of cases (72%) no change in management was indicated as a

result.22

Costs and Implementation

The costs of intraoperative monitors are largely fixed in the acquisition cost of the

monitoring device. Incremental patient costs for disposables are minimal.

Comment

The inability of a very large multicenter study21 to detect a benefit in morbidity and

mortality from pulse oximetry—by all accounts the most useful monitor—suggests that the

magnitude of benefit may be so small that an adequate study to detect this difference may not be

feasible. Along with capnography (carbon dioxide monitoring), pulse oximetry is often cited as

the monitoring method most able to detect potential critical incidents early enough to prevent

adverse outcomes.2,6 This conjecture is supported by the ASA Closed Claims Study. Analyzing

1175 claims, the study concluded that the combination of pulse oximetry and capnography

“could be expected” to help prevent anesthetic-related morbidity and mortality.23

Despite a lack of randomized trial data, the practice of noninvasive intraoperative

monitoring has become standard of care. This has resulted from the ASA Monitoring Standards

and physicians' faith in the practice based on its face value, along with some confirmatory

evidence drawn from incident reporting systems.11,16,17 As such, it seems likely that future

research into intraoperative monitoring will be unable to study approaches that do not include

standard, noninvasive monitoring. Future investigation might seek to determine which

monitoring methods detect “near misses” more effectively.

Moving beyond non-invasive techniques, there is a great need to identify which

specialized monitors provide a safety benefit in selected patient populations. The use of

pulmonary artery catheters for monitoring critically ill patients represents a well-known example

of a practice with substantial face validity but unclear impact on patient outcomes.24,25 In

addition, new, noninvasive alternatives to invasive monitors (eg, esophageal or spirometry-based

cardiac output monitors) may ultimately allow us to obtain the same information at less risk to

the patient.
268

Figure 24.1. ASA standards for basic anesthetic monitoring*

Standard 1: Qualified anesthesia personnel shall be present in the room

throughout the conduct of all general anesthetics, regional anesthetics and

monitored anesthesia care

Standard 2: During all anesthetics, the patient’s oxygenation, ventilation,

circulation, and temperature shall be continually* evaluated

Oxygenation:

Oxygen analyzer for inspired gases

Observation of the patient

Pulse oximetry

Ventilation:

Auscultation of breath sounds

Observation of the patient

Observation of the reservoir bag

Capnography (Carbon dioxide monitoring)

Circulation:

Continuous* ECG display

Heart rate and BP recorded every 5 minutes

Evaluation of circulation

Auscultation of heart sounds

Palpation of pulse

Pulse plethysmography

Pulse oximetry

Intraarterial pressure tracing

Temperature:

Monitor temperature when changes are intended, anticipated, or suspected

* The term “continuous” means prolonged without interruption; "continually"

means repeated regularly and frequently. ECG indicates electrocardiography;

BP, blood pressure.
269

References

1. American Society of Anesthesiologists. Standards of the American Society of

Anesthesiologists: Standards for Basic Anesthetic Monitoring. Available at:

http://www.asahq.org/Standards/02.html. Accessed May 23, 2001.

2. Eichhorn JH. Prevention of intraoperative anesthesia accidents and related severe injury

through safety monitoring. Anesthesiology. 1989;70:572-577.

3. Eichhorn JH. Effect of monitoring standards on anesthesia outcome. Int Anesthesiol Clin.

1993;31:181-196.

4. Keenan RL, Boyan CP. Cardiac arrest due to anesthesia. A study of incidence and causes.

JAMA. 1985;253:2373-2377.

5. Orkin FK. Practice standards: the Midas touch or the emperor's new clothes?

Anesthesiology. 1989;70:567-571.

6. Brodsky JB. What intraoperative monitoring makes sense? Chest. 1999;115:101S-105S.

7. Cohen MM, Duncan PG, Pope WD, Biehl D, Tweed WA, MacWilliam L, et al. The

Canadian four-centre study of anaesthetic outcomes: II. Can outcomes be used to assess the

quality of anaesthesia care? Can J Anaesth. 1992;39:430-439.

8. Phillips OC, Capizzi LS. Anesthesia mortality. Clin Anesth. 1974;10:220-244.

9. Deaths during general anesthesia: technology-related, due to human error, or unavoidable?

An ECRI technology assessment. J Health Care Technol. 1985;1:155-175.

10. National Transportation Safety Board. Aviation Accident Statistics. Available at:

http://www.ntsb.gov/aviation/Stats.htm. Accessed May 28, 2001.

11. Webb RK, van der Walt JH, Runciman WB, Williamson JA, Cockings J, Russell WJ, et al.

The Australian Incident Monitoring Study. Which monitor? An analysis of 2000 incident

reports. Anaesth Intensive Care. 1993;21:529-542.

12. Klepper ID, Webb RK, Van der Walt JH, Ludbrook GL, Cockings J. The Australian

Incident Monitoring Study. The stethoscope: applications and limitations–an analysis of

2000 incident reports. Anaesth Intensive Care. 1993;21:575-578.

13. Cockings JG, Webb RK, Klepper ID, Currie M, Morgan C. The Australian Incident

Monitoring Study. Blood pressure monitoring–applications and limitations: an analysis of

2000 incident reports. Anaesth Intensive Care. 1993;21:565-569.

14. Hewer I, Drew B, Karp K, Stotts N. The utilization of automated ST segment analysis in

the determination of myocardial ischemia. AANA J. 1997;65:351-356.

15. Williamson JA, Webb RK, Cockings J, Morgan C. The Australian Incident Monitoring

Study. The capnograph: applications and limitations–an analysis of 2000 incident reports.

Anaesth Intensive Care. 1993;21:551-557.

16. Spittal MJ, Findlay GP, Spencer I. A prospective analysis of critical incidents attributable

to anaesthesia. Int J Qual Health Care. 1995;7:363-371.

17. Findlay GP, Spittal MJ, Radcliffe JJ. The recognition of critical incidents: quantification of

monitor effectiveness. Anaesthesia. 1998;53:595-598.

18. Asbury AJ, Rolly G. Theatre monitor alarm settings: a pilot survey in Scotland and

Belgium. Anaesthesia. 1999;54:176-180.

19. Silber JH, Kennedy SK, Even-Shoshan O, Chen W, Koziol LF, Showan AM, et al.

Anesthesiologist direction and patient outcomes. Anesthesiology. 2000;93:152-163.

20. Kay J, Neal M. Effect of automatic blood pressure devices on vigilance of anesthesia

residents. J Clin Monit. 1986;2:148-150.
270

21. Moller JT, Johannessen NW, Espersen K, Ravlo O, Pedersen BD, Jensen PF, et al.

Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative events and

postoperative complications. Anesthesiology. 1993;78:445-453.

22. Chambrin MC, Ravaux P, Calvelo-Aros D, Jaborska A, Chopin C, Boniface B.

Multicentric study of monitoring alarms in the adult intensive care unit (ICU): a descriptive

analysis. Intensive Care Med. 1999;25:1360-1366.

23. Tinker JH, Dull DL, Caplan RA, Ward RJ, Cheney FW. Role of monitoring devices in

prevention of anesthetic mishaps: a closed claims analysis. Anesthesiology. 1989;71:541-

546.

24. Connors AF, Speroff T, Dawson NV, Thomas C, Harrell FE, Wagner D, et al. The

effectiveness of right heart catheterization in the initial care of critically ill patients.

SUPPORT Investigators. JAMA. 1996;276:889-897.

25. Ivanov R, Allen J, Calvin JE. The incidence of major morbidity in critically ill patients

managed with pulmonary artery catheters: a meta-analysis. Crit Care Med. 2000;28:615-

619.
271

Chapter 25. Beta-blockers and Reduction of Perioperative Cardiac Events

Andrew D. Auerbach MD, MPH

University of California, San Francisco School of Medicine

Background

As the most common complications of major noncardiac surgery, myocardial infarction

and cardiovascular death have long been a focus of preoperative evaluations1-4 and a target of

perioperative management strategies. Until recently, methods to reduce the incidence of these

complications depended upon preoperative assessments of risk combining clinical evaluation

with clinical prediction rules, followed by additional tests or revascularization procedures, as

appropriate.1

 The benefit of preoperative revascularization remains unclear, as no randomized

prospective trial has demonstrated its benefit.5

 Indeed, concern exists that preoperative

intervention might prove detrimental, as the net benefit in terms of reduced perioperative cardiac

events may be offset by the risks of the revascularization strategy itself. Newer strategies,

including the use of percutaneous transluminal angioplasty as the revascularization modality,

may have promise.6

 Large prospective trials examining these approaches are underway.5

Strong evidence links myocardial ischemia with postoperative myocardial events.7,8 One

study found postoperative ischemia increased the odds of postoperative myocardial events 21-

fold.9

 Based on findings from observational studies that beta-blockade blunts

electrocardiographic signs of ischemia,10-12 recent trials have examined the effects of

perioperative beta-blocker administration on patient outcomes. Results of these investigations

are extremely promising, and beta-blockade may represent an important new method of reducing

perioperative cardiac risk. This chapter reviews the evidence from randomized controlled trials

examining the effect of perioperative beta-blockade on cardiac events (ie, myocardial ischemia,

angina, myocardial infarction, pulmonary edema, and cardiac death).

Practice Description

Although published studies have employed different agents, doses, and dosing schedules,

the general approach in each study has been similar: administration of a therapeutic dose of betablocker prior to induction of anesthesia, followed by beta-blockade through the operation and in

the postoperative period. In all regimens, the dose is titrated to a target heart rate, generally 70

beats per minute or lower.

Prevalence and Severity of the Target Safety Problem

Myocardial cardiac events are the most common medical complication of surgery,

occurring in 2-5% of patients undergoing non-cardiac surgery13 and as many as 30% of patients

undergoing vascular surgery.14,15 Perioperative cardiac events are associated with a mortality rate

of nearly 60% per event,14,16 prolonged hospitalization, and higher costs.16,17 The prevalence of

these events and their high mortality have made the prevention of perioperative cardiac ischemia

the subject of practice guidelines1,17 and numerous prediction rules13,16,18 to detect patients at

high risk for these complications.
272

Opportunities for Impact

As a relatively new therapy, few data describe the use of perioperative beta-blockade in

clinical practice. However, evidence suggests it is utilized infrequently. A recent observational

study in the Netherlands of patients undergoing vascular surgery showed that only 27% of these

high-risk patients received beta-blockers perioperatively.19

Study Designs

Using a structured MEDLINE search, we identified 4 relevant randomized controlled

trials of the effectiveness of perioperative beta-blockade in reducing perioperative cardiac

events, including myocardial ischemia and cardiac or all-cause mortality (Table 25.1). A

randomized trial by Harwood et al was excluded because both groups received beta-blockers (ie,

there was no control group).20 Although data from a study by Wallace et al21 were derived from

one of the randomized trials included in this review,22 it reported effects of beta-blockade upon

different outcomes (ie, myocardial ischemia) and was included in our review. There was

sufficient evidence available to limit the review to studies of Level 1 design. Observational

studies, such as those by Pasternack et al and Boersma et al,11,19 are not included.

Study Outcomes

The studies identified included a range of clinical outcomes: 2 included assessment of

myocardial ischemia12,23 and 3 reported myocardial infarction, pulmonary edema, cardiac death,

or all-cause mortality (Level 1 outcomes).15,22,23

Evidence for Effectiveness of the Practice

Of studies reporting the effect of beta-blockers on perioperative ischemia (Level 2

outcome), all but one found a statistically significant reduction in ischemia among treated

patients. Wallace et al,21 in a subset analysis of data from Mangano et al,24 reported less frequent

perioperative myocardial ischemia in atenolol-treated patients. Stone et al25 suggested a similar

effect of beta-blockade on Holter-monitor documented myocardial ischemia. However, the

authors did not report the types of procedures included in their sample, nor did they statistically

compare baseline patient characteristics, leaving their conclusions open to debate. Raby et al12

also found a significant beneficial effect of beta-blockade using a continuous infusion of esmolol

in high-risk patients undergoing vascular surgery. Although Urban et al also found a reduction in

perioperative ischemia, this difference failed to reach statistical significance.23 These findings

may be explained in part by a relatively low cardiac risk in Urban’s cohort, who were

undergoing elective total knee replacement. The patients in many of the other studies were at

higher risk of cardiac events, as demonstrated by rates of ischemia in the control groups. In

studies finding a statistical difference, rates of ischemia were between 28% and 73% in controls,

as compared with the 15% rate of ischemia observed in Urban's control group.

Of studies reporting cardiac events and cardiac mortality, 2 reported significant

improvement in patient outcomes due to beta-blockade. In a study of male veterans undergoing

major noncardiac surgery, Mangano et al22 reported a relative reduction in all-cause mortality of

nearly 55% at 2 years. This difference, which appeared within the first 8 months of follow-up,

was ascribed to a marked reduction in cardiac events in the first year of therapy (67% reduction

at year 1, 48% at year 2). However, patients in the beta-blocker group had less coronary disease

at study entry, were on ACE-inhibitors more frequently, and were less likely to have betablockers discontinued perioperatively, perhaps biasing results in favor of the treatment group.26,
273

27 Accounting for these differences in multivariate models of varying stringency did not

invalidate their findings.24 Although questions remain about the generalizability of results to

other patient populations, the authors favored broader use of beta-blockade in the setting of

clinical trials.

Poldermans et al15 suggested an even greater benefit of beta-blockade among high-risk

patients. These investigators enrolled patients undergoing vascular surgery who had myocardial

ischemia documented by dobutamine echocardiography, with an estimated rate of perioperative

cardiac event of 28%. The entire patient cohort experienced a 90% reduction in cardiac death or

non-fatal myocardial infarction at 30 days. Follow-up care did not include additional therapy (ie,

cardiac catheterization, revascularization), raising concerns that the research algorithm did not

reflect optimal clinical practice.28, 29 However, if the true rate of events in treated patients is low

(the point estimate from this small study was 3.4%), the risks associated with revascularization30

may outweigh any benefit.

In contrast to the previous 2 studies, Urban et al23 found no statistically significant

difference in rates of in-hospital myocardial infarction. It is likely that these investigators' ability

to detect a difference was limited in part by the relatively small sample size and shorter length of

follow-up. Other studies of perioperative beta-blockade employed longer periods of follow-up to

detect events up to 2 years following surgery.

Differences in absolute magnitude of benefit can be ascribed in part to the cardiac risks

of the patients enrolled (again reflected in event rates in the control groups in each study), with

the most powerful benefits seen in patients at highest risk. The greater benefit seen in

Poldermans et al’s study15 may also be due to the fact that the study did not enroll patients who

were receiving beta-blockers. Patients who are beta-blocker naïve may have a different response

to perioperative use of bisoprolol, or the preexisting use of these agents may represent a

confounding factor not completely accounted for in other studies of perioperative beta-blockade.

Beta-blockade may have additional beneficial effects for elderly patients. Patients who

received beta-blockers were extubated more quickly, required less medication for pain, and were

alert sooner after surgery.31 Although the unblinded nature of this study leaves its findings open

to debate, the possibility of additional benefits is tantalizing and worthy of further investigation.

Potential for Harm

Stone et al reported high rates of bradycardia (21/89 patients) in beta-blocker treated

patients, “half” of whom required atropine therapy. However, the vague descriptions and more

general problems with the study's design make it difficult to interpret the significance of these

events in clinical practice. Adverse events related to the use of beta-blockers in other reviewed

studies were infrequent (10% or less in Mangano et al22) and did not require therapy or result in

withdrawal of the medication. Similar rates of side effects have been noted in studies examining

beta-blockade in patients undergoing cardiac surgery.20,32,33 One study examining use of

propranolol in patients undergoing thoracotomy for pneumonectomy suggested that patients

receiving beta-blockers had twice the rate of postoperative congestive heart failure (4/50 vs.

8/50, p<0.01). In addition, 16% (8/50) of patients in the treatment arm had the drug discontinued

due to “bronchospasm.”

34

Finally, a recent prospective observational study has suggested that withdrawal of betablockade from patients immediately following surgery may result in adverse events.35 This effect

was not observed in randomized trials of beta-blockade that employed shorter treatment

regimens12,25 and should be confirmed by larger studies.
274

Costs and Implementation

The costs of beta-blockers are generally low, and the systems required to use them

according to the protocols used in these studies are already in place. In addition, there is the

potential for significant cost-savings if routine use of beta-blockers allows a safe reduction in the

use of extensive preoperative cardiovascular testing.

Comment

Results from several well-designed clinical trials suggest that use of beta-blockers in the

perioperative period is associated with significant reductions in patient cardiac morbidity and

mortality. In the future such therapy may reduce the need for additional tests and

revascularization procedures,14 further reducing costs of care. However, several questions

regarding its use remain, and should be topics of future research.

First, no clear data suggest an advantage of one particular beta-blocking agent over

another. Studies to date have employed several different beta-blockers, suggesting that the

efficacy of beta-blockade is class dependent if titrated to physiologically active dosages. Other

(alpha-1 selective) sympatholytics also improve patient outcomes,36 raising the possibility that

combined alpha-beta antagonists (ie, labetolol) may have benefit. Second, results from

Shammash et al document the hazards of discontinuation of beta-blockers immediately

postoperatively,35 and most protocols employed treatment regimens that extended longer - even

up to one month following surgery. The current studies suggest beta-blockade should be

continued for at least one week postoperatively. Third, effectiveness of beta-blockade in patients

at high risk due to aortic stenosis or unstable or severe cardiovascular symptoms (New York

Heart Association Class III-IV) is unknown, as these patients were not included in the reviewed

studies. Similarly, its utility - both in terms of cardiac events and cost - in patients with very low

risk of perioperative cardiac events (ie, those undergoing same-day or outpatient surgery,

ophthalmic surgery, or those who have minimal cardiac risk) is unclear. Beta-blockade has not

been studied in patients undergoing regional anesthesia or conscious sedation. In addition, no

study to date has examined the use of beta-blockade in patients who have poor functional status

and might otherwise be referred for additional non-invasive testing.1,5,14,17

Finally, the increasing popularity of perioperative beta-blockade, particularly catalyzed

by the results of the study by Poldermans et al,15 calls into question whether risk stratification

using published guidelines or risk indices is still necessary.28 Although beta-blockade is likely to

be effective in many patients, the identification of patients at highest risk is still important, as

these patients may require additional testing and therapy. A recent study of beta-blockade noted

improved outcomes across a spectrum of predicted cardiac risk, but noted that cardiac events

could be further reduced in high-risk patients through use of additional non-invasive testing and

subsequent “usual care.”

19 Thus, although beta-blockade may increase the threshold at which

clinicians refer patients for additional testing, the era of risk stratification is not over.
275

The use of beta-blockers to reduce perioperative cardiac events and mortality represents a

major advance in perioperative medicine for some patients at intermediate and high risk for

cardiac events during noncardiac surgery. Wider use of this therapy should be promoted and

studied, with future research focused on fine-tuning dosages and schedules and identifying

populations of patients in which its use is cost-effective.
276

Table 25.1. Randomized controlled trials of the effectiveness of perioperative beta-blockade*

Study Participants Regimen Results† Side Effects Comments

Mangano,

199622

Wallace,

199821

200 patients

undergoing

elective

noncardiac

surgery

Atenolol 5-10g IV

30 min before entry

into OR, after

surgery, and 50-

100g qd through

hospital stay (up to

7 days); Target HR

55-65 bpm; doses

held if HR<55 bpm

or SBP<100 mmHg

or defined adverse

event

All-cause

mortality at 2

yrs: 9% vs. 21%

(p=0.019)

Cardiac death at

2 yrs: 4% vs.

12% (p=0.033)

Postoperative

ischemia: 24%

vs. 39%

(p=0.03)

Intraoperative

bradycardia more

common with

atenolol (38% vs.

15%, p=0.0002)

but no difference

in need for

treatment

No increase in

third-degree heart

block,

hypotension,

bronchospasm, or

congestive heart

failure

Included patients

already taking

beta-blockers, an

excess of which

(18 vs. 8%) were

in the beta-blocker

group

NNT 9.1 (primary

endpoint)

Polderman

s, 199915

112 patients with

positive results on

dobutamine

echocardiography

undergoing

elective

abdominal aortic

or infrainguinal

arterial

reconstruction

Bisoprolol 5-10 mg

po qd, begun an

average of 37 days

preoperatively and

continued for 30

days

postoperatively.

Doses held if

HR<50 bpm or

SBP<100 mmHg

Cardiac death:

3.4% vs. 17%

(p=0.02)

Nonfatal MI:

0% vs. 17%

(p<0.001)

No exacerbations

of peripheral

vascular disease

Excluded patients

already on betablockers

NNT 3.2 (cardiac

death or nonfatal

MI)

Raby,

199912

26 patients with

preoperative

ischemia by

Holter monitor

undergoing aortic

aneurysm repair,

infrainguinal

arterial bypass, or

carotid

endarterectomy

Esmolol IV for 48

hr postoperatively.

Titrate to HR 20%

below ischemic

threshold but no

less than 60 bpm

Postoperative

ischemia: 33%

vs. 73%

(p<0.05)

No patient had

beta-blocker

therapy suspended

because of

unacceptable side

effects

Clinicians

prescribed

alternate

postoperative betablockers more

often in control

group (13% vs.

82%, p<0.05)

NNT 2.5 (primary

endpoint)

Stone,

198837

128 untreated

hypertensive

patients

undergoing

elective surgery.

Hypertension

Patients

randomized to

control, labetolol

100 mg po,

atenolol 50 mg po,

or oxprenolol 20

Myocardial

ischemia: 2/89

(2%) vs. 11/39

(28%) in

untreated

patients

21 patients with

beta- blockers had

bradycardia, "half

required atropine."

No bradycardia in

Patients had

generally similar

baseline

characteristics, but

these were not

statistically
277

defined as systolic

blood pressure

160-200 mmHg,

diastolic 90-100

mmHg

mg po given before

induction of

anesthesia

(p<0.001) control patients compared

No description of

surgeries

performed

Urban,

200023

120 patients

undergoing

elective total knee

arthroplasty

Esmolol IV within

1 hr after surgery,

titrate to HR<80

bpm. Change to

metoprolol

morning of 1st

postoperative day.

Titrate to HR<80

bpm for next 48 hrs

then continue dose

until discharge

Postoperative

ischemia: 6%

vs. 15% (p=NS)

Postoperative

MI 2% vs. 6%

(p=NS)

None noted Included patients

already on betablockers (30% in

each arm)

* HR indicates heart rate; MI, myocardial infarction; NNT, number needed to treat; and NS, not

statistically significant.

† Results are reported as beta-blocker group vs. control group.

References

1. Guidelines for assessing and managing the perioperative risk from coronary artery disease

associated with major noncardiac surgery. American College of Physicians. Ann Intern

Med.1997;127:309-312.

2. Belzberg H, Rivkind AI. Preoperative cardiac preparation. Chest. 1999;115:82S-95S.

3. Merli GJ, Weitz HH. The medical consultant. Med Clin North Am. 1987;71:353-355.

4. Merli GJ, Weitz HH. Approaching the surgical patient. Role of the medical consultant. Clin

Chest Med. 1993;14:205-210.

5. Goldman L. Assessing and reducing cardiac risks of noncardiac surgery. Am J Med.

2001;110:320-323.

6. Hassan SA, Hlatky MA, Boothroyd DB, et al. Outcomes of noncardiac surgery after

coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty

Revascularization Investigation (BARI). Am J Med. 2001;110:260-266.

7. Reich DL, Bodian CA, Krol M, Kuroda M, Osinski T, Thys DM. Intraoperative

hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary

artery bypass surgery. Anesth Analg. 1999;89:814-822.

8. Hewer I, Drew B, Karp K, Stotts N. The utilization of automated ST segment analysis in

the determination of myocardial ischemia. Aana J. 1997;65:351-356.

9. Landesberg G, Luria MH, Cotev S, et al. Importance of long-duration postoperative STsegment depression in cardiac morbidity after vascular surgery. Lancet. 1993;341:715-719.
278

10. Smulyan H, Weinberg SE, Howanitz PJ. Continuous propranolol infusion following

abdominal surgery. JAMA. 1982;247:2539-2542.

11. Pasternack PF, Grossi EA, Baumann FG, et al. Beta blockade to decrease silent myocardial

ischemia during peripheral vascular surgery. Am J Surg. 1989;158:113-116.

12. Raby KE, Brull SJ, Timimi F, et al. The effect of heart rate control on myocardial ischemia

among high-risk patients after vascular surgery. Anesth Analg. 1999;88:477-482.

13. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a

simple index for prediction of cardiac risk of major noncardiac surgery. Circulation.

1999;100:1043-1049.

14. Lee TH. Reducing cardiac risk in noncardiac surgery. N Engl J Med. 1999;341:1838-1840.

15. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality

and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch

Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study

Group. N Engl J Med. 1999;341:1789-1794.

16. Goldman L. Multifactorial index of cardiac risk in noncardiac surgery: ten-year status

report. J Cardiothorac Anesth. 1987;1:237-244.

17. Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular

evaluation for noncardiac surgery: an abridged version of the report of the American

College of Cardiology/American Heart Association Task Force on Practice Guidelines.

Mayo Clin Proc.1997;72:524-531.

18. Detsky AS, Abrams HB, Forbath N, Scott JG, Hilliard JR. Cardiac assessment for patients

undergoing noncardiac surgery. A multifactorial clinical risk index. Arch Intern Med.

1986;146:2131-2134.

19. Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular

surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker

therapy. JAMA. 2001;285:1865-1873.

20. Harwood TN, Butterworth J, Prielipp RC, et al. The safety and effectiveness of esmolol in

the perioperative period in patients undergoing abdominal aortic surgery. J Cardiothorac

Vasc Anesth. 1999;13:555-561.

21. Wallace A, Layug B, Tateo I, et al. Prophylactic atenolol reduces postoperative myocardial

ischemia. McSPI Research Group. Anesthesiology. 1998;88:7-17.

22. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and

cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative

Ischemia Research Group. N Engl J Med. 1996;335:1713-1720.

23. Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligfield P. Postoperative

prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial

ischemia. Anesth Analg. 2000;90:1257-1261.

24. Mangano DT. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac

surgery. N Engl J Med. 1997;336:1452.

25. Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L. Myocardial ischemia in

untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic

blocking agent. Anesthesiology. 1988;68:495-500.

26. Reis SE, Feldman AH. Effect of atenolol on mortality and cardiovascular morbidity after

noncardiac surgery. N Engl J Med. 1997;336:1453.

27. Petros JA. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac

surgery. N Engl J Med. 1997;336:1452.
279

28. Litwack R, Gilligan D, DeGruttola V. Beta-Blockade for patients undergoing vascular

surgery. N Engl J Med. 2000;342:1051-1053.

29. Feldman T, Fusman B, McKinsey JF. Beta-Blockade for patients undergoing vascular

surgery. N Engl J Med. 2000;342:1051-1052.

30. Poldermans D, Boersma E. Beta-Blockade for patients undergoing vascular surgery. N

Engl J Med. 2000;342:1052-1053.

31. Zaugg M, Tagliente T, Lucchinetti E, et al. Beneficial effects from beta-adrenergic

blockade in elderly patients undergoing noncardiac surgery. Anesthesiology. 1999;91:1674-

1686.

32. Hammon JW, Wood AJ, Prager RL, Wood M, Muirhead J, Bender HW. Perioperative beta

blockade with propranolol: reduction in myocardial oxygen demands and incidence of

atrial and ventricular arrhythmias. Ann Thorac Surg. 1984;38:363-367.

33. Lamb RK, Prabhakar G, Thorpe JA, Smith S, Norton R, Dyde JA. The use of atenolol in

the prevention of supraventricular arrhythmias following coronary artery surgery. Eur

Heart J. 1988;9:32-36.

34. Bayliff CD, Massel DR, Inculet RI, et al. Propranolol for the prevention of postoperative

arrhythmias in general thoracic surgery. Ann Thorac Surg. 1999;67:182-186.

35. Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE. Perioperative betablocker withdrawal and mortality in vascular surgical patients. Am Heart J. 2001;141:148-

153.

36. Oliver MF, Goldman L, Julian DG, Holme I. Effect of mivazerol on perioperative cardiac

complications during non-cardiac surgery in patients with coronary heart disease: the

European Mivazerol Trial (EMIT). Anesthesiology. 1999;91:951-961.

37. Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L. Risk of myocardial

ischaemia during anaesthesia in treated and untreated hypertensive patients. Br J Anaesth.

1988;61:675-679.
280

Section D. Safety Practices for Hospitalized or Institutionalized Elders

Chapter 26. Prevention of Falls in Hospitalized and Institutionalized Older People

Subchapter 26.1. Identification Bracelets for High-Risk Patients

Subchapter 26.2. Interventions that Decrease the Use of Physical Restraints

Subchapter 26.3. Bed Alarms

Subchapter 26.4. Special Hospital Flooring Materials to Reduce Injuries from

Patient Falls

Subchapter 26.5. Hip Protectors to Prevent Hip Fracture

Chapter 27. Prevention of Pressure Ulcers in Older Patients

Chapter 28. Prevention of Delirium in Older Hospitalized Patients

Chapter 29. Multidisciplinary Geriatric Consultation Services

Chapter 30. Geriatric Evaluation and Management Units for Hospitalized Patients
281

Chapter 26. Prevention of Falls in Hospitalized and Institutionalized

Older People

Joseph V. Agostini, MD

Dorothy I. Baker, PhD, RNCS

Sidney T. Bogardus, Jr., MD

Yale University Schools of Medicine and Public Health

Introduction

A fall is defined as unintentionally coming to rest on the ground, floor, or other lower

level, but not as a result of syncope or overwhelming external force. Falling is a common cause

of morbidity and the leading cause of nonfatal injuries and trauma-related hospitalizations in the

United States.1

 Complications include bone fractures, injury to the soft tissues, increased

functional dependence, and fear of falling again, which itself can be debilitating. Each of these

complications contributes to increased risk of future falls. Studies in community-dwelling older

patients have identified age, gait or balance impairment, sensory or cognitive impairment,

musculoskeletal diseases, environmental hazards, and many medications (such as sedativehypnotic drugs) as risk factors.

One of the strongest predictors of future falls is having previously fallen. There are

numerous other risk factors for falls in older persons, which are reviewed in detail elsewhere.2,3

The number of risk factors is correlated with the risk of falling. A study by Tinetti and

colleagues found the risk of falling increased from 19% when one risk factor was present to 78%

in the presence of 4 or more risk factors.4

 Some of the factors associated with fall risk in the

hospital setting, however, may differ from those in community-dwelling or institutional settings.

The onset of an acute illness leading to hospitalization may increase fall risk due to immobility

and deconditioning. Treatment for an acute condition, such as the addition of new medications or

an altered medication regimen, may also increase fall risk.

The hospital environment itself may either be a supportive environment (eg, the presence

of handrails and no-slip bathing surfaces) or may contribute to fall risk (eg, unfamiliar rooms,

improper bed height). This chapter reviews general evidence regarding multicomponent falls

prevention protocols, and 5 specific interventions: identification bracelets, physical restraints,

bed alarms, special flooring, and hip protectors.

Prevalence and Severity of the Target Safety Problem

Falls are among the most common incidents reported in institutions,5

 although incident

reports may underestimate their true occurrence.6

 The incidence of falls among hospitalized

patients varies according to the risk factors and case mix of the patient population as well as the

presence of falls prevention measures. Rubinstein has reported fall rates of 0.6 to 2.9 falls

annually per bed in hospitalized patients and 0.6 to 3.6 falls annually per bed in long-term care

institutions, based on published data.7

 About 50% of the 1.7 million nursing home residents in

the United States fall at least once each year, resulting in serious injury in about 10% of

residents.7-9 The total cost of falls injuries in 1994 for adults aged 65 years and older was

estimated at $20.2 billion.10

Hip fractures are the most feared complication of falls. Up to 20% of people sustaining a

hip fracture become nonambulatory, and only 14-21% recover their ability to carry out
282

instrumental activities of daily living.11 The estimated total incremental costs (the difference

between costs before and after a hip fracture) of caring for an individual in the year after fracture

were estimated to be between $16,300 and $18,700.12 Estimated Medicare expenditures for hip

fractures in 1991 were about $2.9 billion.13

Practice Description

Based on the multifactorial etiology of falls, multicomponent interventions have been

developed to address patient risk factors and decrease fall rates. However, most studies have not

been designed in a way to determine which components of a multicomponent intervention are

most effective.

Risk Assessment

A variety of institution-based programs have been implemented to prevent falls. These

programs usually begin by identifying individuals at increased risk for falling. This is

accomplished by history-taking to elicit past falls history or by using more formal assessment

tools.4,14-17 Protocols used to perform falls risk assessment in hospitals or nursing homes vary by

institution and often have not been validated.18

Community-Dwelling Elders

An overwhelming majority of the large, prospective, controlled studies have been carried

out in the outpatient environment. They deserve mention because many of the interventions

could be modified for a hospital-based intervention. Tinetti and colleagues19 showed that

interventions to reduce specific risk factors resulted in a 30% reduction in falls over one year in a

prospective community cohort. The targeted risk factors were postural hypotension, use of any

benzodiazepine or sedative-hypnotic drug, use of 4 or more prescription medications,

environmental hazards, and muscular strength or range of motion impairments. Specific

interventions that were part of the multicomponent program included exercise recommendations,

behavioral recommendations, medication review, and environmental modifications. A systematic

review of predominantly non-hospital based multi-risk factor intervention studies showed

significant protection against falling (Peto OR 0.77, 95% CI: 0.64-0.91).20 There was, however,

significant heterogeneity across studies.

The large literature on community-based interventions has yielded other insights, some of

which may be applicable to the acute care setting. For example, exercise-based interventions21-25

have been studied as a means to decrease falls in older persons. Results of these trials have not

been conclusive. A pre-planned meta-analysis of 7 randomized controlled trials (2 nursing homebased and 5 community-based) that included an exercise component found a 10% decrease in

fall risk (adjusted incidence ratio 0.90, 95% CI: 0.81-0.99),26 although a recent systematic review

examining the effect of 4 trials of exercise alone found no protection against falling.20 Another

important insight from primarily non-hospital settings includes the association between specific

medications or classes of medications and falls.27,28 Although several studies have used

pharmacist- or physician-based medication reviews as part of a multifaceted intervention, the

independent effect of medication review and adjustment on fall outcomes has not been reported.

Institutionalized Elders

In a nursing home setting, a promising randomized controlled trial incorporating

individualized assessment and targeting 4 falls-associated domains has been reported.29

Intervention facilities had 19% fewer recurrent falls (95% CI: 2%-36%) compared with control
283

facilities and a 31% reduction in mean rate of injurious falls (13.7 vs. 19.9 falls per 100 personyears; p=0.22). Interventions in this study were made in the areas of environmental and personal

safety (improvement in room lighting, flooring, footwear), wheelchair use and maintenance

(assessment by an occupational therapist), psychotropic drug prescription (assessment and

recommendations for change), transfer and ambulation (evaluation and recommendations for

change), and facility-wide interventions (eg, in-service educational programs). No analogous

study of a multi-intervention standardized protocol has been reported in hospitalized patients.

Hospitalized Elders

In the hospital, interventions have been employed as part of multiple risk factor

intervention studies, but many have been poorly described and standardized. In the studies set in

acute care environments,30-45 practices include educational activities for nurse and support staff,

patient orientation activities, review of prior falls, and improvement of surrounding environment.

Specific environmental components included decreasing ward or room obstacles, adding

supplemental lighting and grab bars in bathrooms, and lowering bedrails and bed height. Other

studies have attempted to improve transfer and mobility by providing scheduled ambulatory and

physical therapy activities and better footwear (eg, non-skid socks). Additionally, studies have

incorporated strategies to assist cognitively impaired patients by educating family members to

deal with confused patients, minimizing sedating medications, and moving confused patients

closer to nursing staff. Because many of these hospital studies use small sample sizes and

inadequately describe the precise number and standardization of interventions, their

generalizability and reproducibility is limited. However, a recent systematic review of many of

these programs concluded that a pooled effect of 25% reduction in the fall rate occurred in the

studies that examined prospective interventions compared to fall risk in historical controls.18

Some interventions with the potential for effectiveness in isolation have been studied.

Each of the following hospital- or institution-based individual interventions has been analyzed

independently of a multi-component falls prevention program:

• Identification bracelets

• Physical restraints

• Bed alarms

• Special flooring

• Hip protectors

Several generally accepted interventions with high face-validity have not been

independently studied, yet are commonly accepted practices. Immobility46 is a significant risk

factor for several geriatric complications, including falls, pressure ulcers, and functional decline.

Minimization of bedrest is a practical, real-world intervention that has implications for

prevention of a number of serious hospital-acquired complications.47

Comment

There are few hospital or other institution-based randomized controlled trials of

standardized falls interventions, although the necessity for well-designed studies is clear. The

nursing home-based intervention reported by Ray and colleagues29 provides good evidence that a

well-documented intervention can improve falls outcomes in institutionalized patients. No

similarly designed trial of a multicomponent intervention in hospitalized patients was identified,

although many falls prevention programs incorporate multifactorial interventions. The questions

raised by multicomponent falls prevention studies include the generalizability of interventions to
284

diverse inpatient settings, appropriate targeting of at-risk individuals, analysis of the individual

components that provide the best improvement in falls outcomes, and the transportability of

interventions between institutions with variable resources for implementation. Evidence for the

effectiveness of individual interventions is important, but effectiveness may change (for better or

worse) when such interventions are incorporated with others as part of a falls prevention

program.

Subchapter 26.1. Identification Bracelets for High-Risk Patients

Background

Some hospitals use colored bracelets to identify patients at high risk for falls. Other

identification methods include signs, stickers, or tags placed above the patient’s bed, at the

nursing station, or on the patient’s chart. In theory, these remind staff that the patient is at high

risk for falls and trigger interventions that reduce the risk of falls (eg, supervision or assistance

with ambulation, minimization of sedative-hypnotic medications, lowering of bed height).

Identification bracelets might also impact patients’ falls awareness (eg, reminding patients to call

for assistance before getting out of bed).

Prevalence and Severity of the Target Safety Problem

See Introduction to Chapter 26.

Opportunities for Impact

We found no published data on the number of hospitals currently using such strategies.

Practice Description and Evidence for Effectiveness

A search of the literature identified many studies that have used identification bracelets,

signs, or tags for high-risk patients.31-33,35,40-42,44,45,48,49 Most of these involved multiple,

simultaneous interventions and were designed such that estimation of the treatment effect due to

the identification bracelet, signs or tags component cannot be calculated. The remaining study

was a randomized, controlled trial of colored identification bracelets worn by inpatients at high

risk for falls (Table 26.1.1).50 “High-risk” was defined as history of multiple falls, an episode of

incontinence, or an admitting diagnosis of stroke or ataxia. Cox proportional hazards model was

used to assess the effect of identification bracelets on time-to-first-fall. The fall rate was 42%

(27/65) in the intervention group and 30% (21/69) in the control group, which did not represent a

statistically significant difference. After preliminary analysis of the data, the investigators and

ethics committee agreed that it was not appropriate to continue for the sole purpose of obtaining

statistical power, and the study was terminated.

Potential for Harm

None identified.

Costs and Implementation

Identification tags and similar interventions are associated with minimal costs.

Comment

Use of special bracelets, signs, and stickers to identify patients at high risk for falls is a

relatively inexpensive and easy to implement practice. There is currently insufficient information
285

as to whether identification bracelets, as a isolated intervention, decrease falls. Future studies

should assess the effectiveness of similar identification strategies in the context of

multicomponent fall prevention programs and, if they are effective, which methods work best.

Table 26.1.1. Study of identification bracelets*

Study Participants and Setting Study Design,

Outcomes

Results

Mayo,

199450

134 high-risk patients in a

rehabilitation hospital, 1990-91

Level 1,

Level 1

Hazard ratio for fall with

intervention: 1.3 (95% CI: 0.8-2.4)

* CI indicates confidence interval.

References

1. Baker SP, O'Neill B, Ginsburg MJ, Guohua L. The injury fact book. 2nd edition. New

York: Oxford University Press, 1992.

2. Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med.

1989;320:1055-9.

3. Myers AH, Young Y, Langlois JA. Prevention of falls in the elderly. Bone. 1996;18:87S101S.

4. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living

in the community. N Engl J Med. 1988;319:1701-1707.

5. Sutton J, Standan P, Wallace A. Incidence and documentation of patient accidents in

hospital. Nurs Times. 1994;90:29-35.

6. Kanten DN, Mulrow CD, Gerety MB, Lichtenstein MJ, Aguilar C, Cornell JE. Falls: an

examination of three reporting methods in nursing homes. J Am Geriatr Soc.

1993;41:662-666.

7. Rubenstein LZ, Robbins AS, Schulman BL, Rosado J, Osterweil D, Josephson KR. Falls

and instability in the elderly. J Am Geriatr Soc.1988;36:266-278.

8. Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Ann Intern Med.

1994;121:442-451.

9. Tinetti ME. Factors associated with serious injury during falls by ambulatory nursing

home residents. J Am Geriatr Soc. 1987;35:644-648.

10. Englander F, Hodson TJ, Terregrossa RA. Economic dimensions of slip and fall injuries.

J Forensic Sci. 1996; 41:733-746.

11. Zuckerman JD. Hip fracture. N Engl J Med. 1996;334:1519-1525.

12. Brainsky GA, Lydick E, Epstein R, et al. The economic cost of hip fractures in

community-dwelling older adults: a prospective study. J Am Geriatr Soc.1997;45:281-

287.

13. CDC. Incidence and costs to Medicare of fractures among Medicare beneficiaries aged >

65 years: United States, July 1991-June 1992. MMWR - Morbidity & Mortality Weekly

Report 1996;45:877-883.

14. Oliver D, Britton M, Seed P, Martin FC, Hopper AH. Development and evaluation of

evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will

fall: case-control and cohort studies. BMJ. 1997;315:1049-1053.

15. Whitney SL, Poole JL, Cass SP. A review of balance instruments for older adults. Am J

Occup Ther. 1998;52: 666-671.
286

16. Shumway-Cook A, Baldwin M, Polissar NL, Gruber W. Predicting the probability for

falls in community-dwelling older adults. Phys Ther. 1997;77:812-819.

17. Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J

Am Geriatr Soc. 1986;34:119-126.

18. Oliver D, Hopper A, Seed P. Do hospital fall prevention programs work? A systematic

review. J Am Geriatr Soc. 2000;48:1679-1689.

19. Tinetti ME, Baker DI, McAvay G, et al. A multifactorial intervention to reduce the risk

of falling among elderly people living in the community. N Engl J Med. 1994;331:821-

827.

20. Gillespie LD, Gillespie WJ, Cumming R, Lamb SE, Rowe BH. Interventions for

preventing falls in the elderly. In: The Cochrane Library, Issue 2, 2000. Oxford: Update

Software.

21. McMurdo ME, Mole P, Paterson C. Controlled trial of weight-bearing exercise in older

women in relation to bone density and falls. BMJ. 1997;314:569.

22. Wolf SL, Barnhart HX, Kutner NG, McNeely E, Coogler C, Xu T. Reducing frailty and

falls in older persons: an investigation of Tai Chi and computerized balance training.

Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention

Techniques. J Am Geriatr Soc.1996;44:489-497.

23. Lord SR, Ward JA, Williams P, Strudwick M. The effect of a 12-month exercise trial on

balance, strength, and falls in older women: a randomized controlled trial. J Am Geriatr

Soc. 1995;43:1198-1206.

24. Reinsch S, MacRae P, Lachenbruch PA, Tobis JS. Attempts to prevent falls and injury: a

prospective community study. Gerontologist. 1992;32:450-456.

25. Mulrow CD, Gerety MB, Kanten D, et al. A randomized trial of physical rehabilitation

for very frail nursing home residents. JAMA. 1994;271:519-524.

26. Province MA, Hadley EC, Hornbrook MC, et al. The effects of exercise on falls in

elderly patients. A preplanned meta-analysis of the FICSIT Trials. Frailty and Injuries:

Cooperative Studies of Intervention Techniques. JAMA. 1995;273:1341-1347.

27. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic

review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc.1999;47:30-39.

28. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic

review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc. 1999;47:40-

50.

29. Ray WA, Taylor JA, Meador KG, et al. A randomized trial of a consultation service to

reduce falls in nursing homes. JAMA. 1997;278:557-562.

30. Rainville NG. Effect of an implemented fall prevention program on the frequency of

patient falls. Qual Rev Bull. 1984;10:287-291.

31. Fife DD, Solomon P, Stanton M. A risk/falls program: code orange for success...geriatric

patients. Nurs Manage. 1984;15:50-53.

32. Barker SM, O'Brien CN, Carey D, Weisman GK. Quality improvement in action: a falls

prevention and management program. Mt Sinai J Med. 1993;60:387-90.

33. Hendrich AL. An effective unit-based fall prevention plan. J Nurs Qual Assur.

1988;3:28-36.

34. Craighead J, Fletcher P, Maxwell J. Seven steps for fall prevention. Dimens Health Serv.

1991;68:25-26.

35. Kilpack V, Boehm J, Smith N, Mudge B. Using research-based nursing interventions to

decrease patient falls. Appl Nurs Res. 1991;4:50-56.
287

36. Mitchell A, Jones N. Striving to prevent falls in an acute care setting–action to enhance

quality. J Clin Nurs. 1996;5:213-220.

37. Hill BA, Johnson R, Garrett BJ. Reducing the incidence of falls in high risk patients. J

Nurs Adm. 1988;18:24-28.

38. Hernandez M, Miller J. How to reduce falls. Geriatr Nurs. 1986;7:97-102.

39. Krishna KM, Van Cleave RJ. Decrease in the incidence of patient falls in a geriatric

hospital after educational programs [letter]. J Am Geriatr Soc.1983;31:187.

40. Morton D. Five years of fewer falls. Am J Nurs. 1989;89:204-205.

41. Sweeting HL. Patient fall prevention–a structured approach. J Nurs Manag. 1994;2:187-

92.

42. Schmid NA. Reducing patient falls: a research-based comprehensive fall prevention

program. Mil Med. 1990;155:202-207.

43. Brady R, Chester FR, Pierce LL, Salter JP, Schreck S, Radziewicz R. Geriatric falls:

prevention strategies for the staff. J Gerontol Nurs. 1993;19:26-32.

44. Cannard G. Falling trend. Nurs Times. 1996;92:36-37.

45. Zepp S. "Ban a fall." A nursing innovation to reducing patient falls. Kans Nurse.

1991;66:13.

46. Mahoney JE. Immobility and falls. Clin Geriatr Med.1998;14:699-726.

47. Harper CM, Lyles YM. Physiology and complications of bed rest. J Am Geriatr Soc.

1988;36:1047-1054.

48. Rogers S. Reducing falls in a rehabilitation setting: a safer environment through team

effort. Rehabil Nurs. 1994;19:274-276,322.

49. Innes E. Maintaining fall prevention. QRB. 1985;11:217-221.

50. Mayo NE, Gloutney L, Levy AR. A randomized trial of identification bracelets to

prevent falls among patients in a rehabilitation hospital. Arch Phys Med Rehabil.

1994;75:1302-1308.

Subchapter 26.2. Interventions that Decrease the Use of Physical Restraints

Background

The Health Care Financing Administration (HCFA) defines physical restraints as “any

manual method or physical or mechanical device, material, or equipment attached or adjacent to

the patient that the individual cannot remove easily which restricts freedom of movement or

normal access to one’s body.”

1 Physical restraints have been used in nursing homes and hospitals

both as a safety device and as a falls prevention tool. Because restrained patients cannot arise

from a chair or transfer out of bed, they theoretically will not fall or, in the case of bedrails, will

not roll out of bed. However, the use of physical restraints may lead to substantial adverse

outcomes. In fact, serious injuries and even death have been reported with use of these devices.2,3

This chapter examines interventions to reduce use of physical restraints and the concomitant

effect on fall rates.

Practice Description

Studies examining the use physical restraints have considered 2 types of interventions in

hospital or nursing home settings: bedrails and other mechanical restraints designed to restrict

mobility. These interventions usually begin with either a physician or nurse making an

assessment that a patient is at risk for falls, elopement, or other adverse outcomes. Thereafter,
288

use of a restraint is initiated, with periodic reassessment of the ongoing need for the device.

Safety practices to reduce restraint use in nursing home patients have included nursing education

strategies focusing on assessment/reassessment of the need for restraints and the use of

alternatives to restraints.

Prevalence and Severity of the Target Safety Problem

See Introduction to Chapter 26.

Opportunities for Impact

Federal guidelines now discourage all but the limited, appropriate use of physical

restraints and bedrails. Legislation adopted as part of the Omnibus Budget Reconciliation Act of

1987 directed nursing homes to limit physical restraints, and the Joint Commission on the

Accreditation of Healthcare Organizations (JCAHO) has adopted similar guidelines. Several

statewide initiatives (eg, the Pennsylvania Restraint Reduction Initiative, begun in 1996) have

been implemented under HCFA’s National Restraint Reduction Initiative, resulting in notable

reductions in restraint usage.4

 The Food and Drug Administration’s Hospital Bed Safety Work

Group has likewise actively raised awareness of the risks and benefits of bedrail use.5

 Based on

an annual HCFA survey, the national restraint rate was approximately 13.5% in 1999, down

from approximately 20% in 1996 when HCFA’s Restraint Reduction Initiative began.6

Nonetheless, data from selected states reveals that the rate was still as high as 26% as of 1998.7

Study Designs and Outcomes

Six studies were identified: 2 concerning bedrail interventions8,9 and 4 describing

mechanical restraints interventions (Table 26.2.1).7,10-12 Most studies compare interventions with

historical control or baseline rates using a before-after study design. Morbidity data on falls are

reported in all studies.

Evidence for Effectiveness of the Practice

The studies reveal no statistically significant difference in falls compared with historical

controls when bedrails are removed. In fact, restrained patients appear to have a modest increase

in fall risk or fall injuries based on several studies. Weaknesses in study design for some of these

studies preclude a final conclusion.

Potential for Harm

The potential for harm with use of bedrails is well-documented, including death from a

variety of mechanisms, including death and strangulation.13 Mechanical restraints likewise carry

a risk of severe injury, strangulation, and mobility limitations that may predispose patients to

other adverse outcomes (pressure ulcers, incontinence, acute confusion). Limits to patient

freedom, dignity, and quality of life also contribute to the potential for harm. A potential harm of

interventions to decrease restraint use is that there may be an increase in other adverse events

(eg, elopement) if appropriate alternative preventive measures are not in place.

Costs and Implementation

The costs associated with interventions to reduce the use of restraints have not been

described. Nonetheless, reduction in the use of physical restraints will require resources to pay

for alternative interventions and rehabilitative measures and will increase labor costs.14

Compliance with interventions to reduce bedrail rates and to decrease mechanical restraint use
289

has been good. In fact, given adequate alternatives to the use of these devices, hospital and

nursing staffs have decreased their usage significantly. In the Neufeld study,7

 for example,

restraint use fell from 41% to 4%.

Comment

There is growing evidence that physical restraints have a limited role in medical care.

Restraints limit mobility, a shared risk factor for a number of adverse geriatric outcomes, and

increase the risk of iatrogenic events. They certainly do not eliminate falls, and decreasing their

use can be accomplished without increasing fall rates. In some instances reducing the use of

restraints may actually decrease the risk of falling. Incorporating changes into physician and staff

behavior may be easier if large, multicenter trials are successful in identifying safe alternatives to

restraints that effectively limit falls risks for patients.
290

Table 26.2.1. Studies of physical restraints and fall risk*

Study Participants and Setting Design,

Outcomes

Results

Hanger,

19999

1968 hospital patients in New

Zealand, 1994; formal bedrail

policy and educational

program to reduce bedrail use,

historical controls

Level 3,

Level 1 No significant difference in overall fall

rate: 164.8 falls/10,000 bed days

before and 191.7 falls/10,000 bed

days after the intervention (p=0.18)

Fewer serious falls occurred after the

intervention (p=0.008)

Si, 19998 246 patients in a teaching

nursing home, 1993-94;

interdisciplinary team

assessment and removal of

bedrails with provision of

bedrail alternatives, historical

controls

Level 3,

Level 1

No significant difference in fall rates:

2/116 (1.7%) patients before and

2/130 (1.5%) patients after the

intervention

Capezuti,

199611

322 nursing home residents;

subgroup of confused patients

examined for mechanical

restraint use

Level 3,

Level 1

Confused patients who were restrained

had increased odds of falling (OR

1.65, 95% CI: 0.69-3.98) and

recurrent falls (OR 2.46, 95% CI:

1.03-5.88)

Capezuti,

199812

633 nursing home residents in

3 nursing homes, 1990-1991;

restraint education and

consultation interventions

compared with baseline rates

Level 3,

Level 1

No significant increase in fall rates in

the restraint-free group

Decreased odds of minor injury after

restraint removal, adjusted OR 0.3

(95% CI: 0.1-0.9)

Neufeld,

19997

2075 nursing home beds in 16

nursing homes, 1991-1993;

educational intervention to

decrease mechanical restraints

compared with baseline rates

Level 3,

Level 1

Moderate/severe injuries decreased

from 7.4% to 4.4% (p=0.0004) after

educational intervention

Tinetti,

199110

397 elderly patients at 12

skilled nursing facilities;

observational cohort study of

mechanical restraint use

Level 3,

Level 1

15/275 (5%) of unrestrained patients

compared to 21/122 (17%)

experienced a serious fall-related

injury (p<0.001)

Restraint use was significantly

associated with a serious fall,

adjusted OR 10.2 (95% CI: 2.8-36.9)

* CI indicates confidence interval; OR, odds ratio.
291

References

1. Health Care Financing Administration. FY 2001 Annual Performance Plan. Available at:

http://www.hcfa.gov/stats/2001.htm. Accessed June 13, 2001.

2. FDA Center for Devices and Radiological Health. FDA safety alert: entrapment hazards

with hospital bed side rails. August 1995. Available at: http://www.fda.gov/cdrh/

bedrails.html. Accessed June 12, 2001.

3. Miles SH, Irvine P. Deaths caused by physical restraints. Gerontologist. 1992;32:762-766.

4. Health Care Financing Administration. National restraint reduction newsletter. Summer

2000. Available at: http://www.hcfa.gov/publications/newsletters/restraint/2000/

rr0600.asp. Accessed June 12, 2001.

5. FDA Center for Devices and Radiological Health. A guide to bed safety. Available at:

http://www.fda.gov/cdrh/beds/bedrail.pdf. Accessed June 12, 2001.

6. Health Care Financing Administration. National restraint reduction newsletter. Winter

1999. Available at: http://www.hcfa.gov/publications/newsletters/restraint/1999/

rrwin99.htm. Accessed June 12, 2001.

7. Neufeld RR, Libow LS, Foley WJ, Dunbar JM, Cohen C, Breuer B. Restraint reduction

reduces serious injuries among nursing home residents. J Am Geriatr Soc. 1999;47:1202-

1207.

8. Si M, Neufeld RR, Dunbar J. Removal of bedrails on a short-term nursing home

rehabilitation unit. Gerontologist. 1999;39:611-614.

9. Hanger HC, Ball MC, Wood LA. An analysis of falls in the hospital: can we do without

bedrails? J Am Geriatr Soc. 1999;47:529-531.

10. Tinetti ME, Liu YB, Ginter S. Mechanical restraint use and fall related injuries among

residents of skilled nursing facilities. Ann Intern Med. 1992;116:369-374.

11. Capezuti E, Evans L, Strumpf N, Maislin G. Physical restraint use and falls in nursing

home residents. J Am Geriatr Soc. 1996;44:627-633.

12. Capezuti E, Strumpf NE, Evans LK, Grisso JA, Maislin G. The relationship between

physical restraint removal and falls and injuries among nursing home residents. J Gerontol

A Biol Sci Med Sci. 1998;53:M47-M52.

13. Parker K, Miles SH. Deaths caused by bedrails. J Am Geriatr Soc. 1997;45:797-802.

14. Schnelle JF, Smith RL. To use physical restraints or not? [editorial]. J Am Geriatr Soc.

1996;44:727-728.

Subchapter 26.3. Bed Alarms

Background

Epidemiologic studies reveal that falls occur commonly in and around bed areas.1,2

Decreasing the risk of falls when patients attempt to transfer into and out of bed without

assistance is a potentially important target safety goal. This chapter examines the use of a bed

alarm system that alerts hospital staff to patient movement out of bed as a strategy to reduce

falls. General principles of alarm use in health care settings can be found in Chapter 8.
292

Practice Description

A sensor device is placed on the bed, under a sitting or reclining patient. When the

patient changes position, it detects movement and/or absence of weight. An audible alarm is

triggered at the nurses’ station and, with some devices, in the patient’s room. The alarm alerts

nurses when patients attempt to leave the bed without assistance and may alert a patient to

remain in bed if the alarm is audible in the patient’s room.

Evidence for Effectiveness of the Practice

Several studies have included bed alarms as part of a multifaceted intervention.3-6

However, the study designs do not allow calculation of the effect attributable to the bed alarm

component or were not controlled. A recent, unpublished before-after study was identified in a

Web search but the full report could not be obtained before completion of this chapter.7

Tideiksaar et al randomized elderly patients at “high risk” for falls to either a group that received

an alarm system (the RN+ OnCall bed monitoring system) or to a control group that did not

(Table 26.3.1)8

. The groups were similar in age and gender. No other baseline comparisons were

reported. There were fewer falls in the study group but the difference failed to reach statistical

significance. However, the total number of falls was low (n=17) and had there been one less fall

in the alarm group or one more fall in the control group, the difference would have been

statistically significant.

Potential for Harm

No harm was identified. There are theoretical electrical risks if the sensor devices are

internally compromised due to bending of the sensor mats and exposure to fluids, but such

events have not been reported in the literature.

Costs and Implementation

Costs of the devices vary by manufacturer, the type of bed monitoring system used, and

the number of beds to be monitored. Manufacturers’ charges range from several hundred to

several thousand dollars for the receiving equipment. Individual sensors require replacement

after pre-specified periods of use or, in some cases, can be cleaned between patients, which

incurs additional hospital costs. Implementation requires adequate staffing to respond in a timely

manner to the audible alarms.

Comment

At this time, there is insufficient evidence regarding the effectiveness of bed alarms in

preventing falls in elderly patients to recommend the practice. Additional research sufficiently

powered to identify meaningful differences, coupled with a formal economic analysis, would be

useful.
293

Table 26.3.1. Study of bed alarms for fall prevention

Study Participants and Setting Study Design,

Outcomes

Results

(95% Confidence Interval)

Tideiksaar,

19938

70 patients on a geriatric unit in

a university hospital, 1992

Level 1,

Level 1 Odds ratio for prevention of

falls: 0.32 (0.10-1.03)

References

1. Vassallo M, Amersey RA, Sharma JC, Allen SC. Falls on integrated medical wards.

Gerontology. 2000;46:158-162.

2. Sutton J, Standan P, Wallace A. Incidence and documentation of patient accidents in

hospital. Nurs Times. 1994;90:29-35.

3. Schmid NA. Reducing patient falls: a research-based comprehensive fall prevention

program. Mil Med. 1990;155:202-207.

4. Widder B. A new device to decrease falls. Geriatr Nurs. 1985;6:287-288.

5. Morton D. Five years of fewer falls. Am J Nurs. 1989;89:204-205.

6. Innes E. Maintaining fall prevention. QRB. 1985;11:217-221.

7. Bed-Check Corporation. Fall prevention study: bed alarms, investigating their impact on

fall prevention and restraint use. Available at: http://www.bedcheck.com/fall-preventionstudy.html. Accessed June 6, 2001.

8. Tideiksaar R, Feiner CF, Maby J. Falls prevention: the efficacy of a bed alarm system in an

acute-care setting. Mt Sinai J Med. 1993;60:522-527.

Subchapter 26.4. Special Hospital Flooring Materials to Reduce Injuries from Patient

Falls

Background

One proposed practice to prevent injury due to falls is to alter flooring material on

hospital wards or in nursing homes. Carpeting, vinyl, or other biomedically-engineered materials

could potentially improve falls outcomes. The use of special flooring materials has been shown

to influence specific gait characteristics in hospitalized elders.1

 A recent study described the

Penn State Safety Floor, which is designed to remain relatively rigid under normal walking

conditions but to deform elastically to absorb impact forces during a fall.2

 The efficacy of this

floor is still being tested outside the laboratory environment among nursing home residents.3

Practice Description

As data on the efficiency of the Penn State Safety Floor2

 are not yet available, we restrict

our review to the use of hospital-duty carpeting compared with “usual” vinyl flooring.
294

Study Designs and Outcomes

We identified 2 studies of the effect of flooring type (carpet vs. “usual” vinyl flooring) on

falls: a randomized controlled trial in an inpatient rehabilitation unit4

 and a retrospective study of

accidents reported in a care of the elderly unit (Table 26.4.1).5

 Both studies reported Level 1

outcomes. The randomized trial measured the rate of falls. The retrospective analysis studied

fall-related injury, defined as any graze, bruise, laceration, fracture or pain.

Evidence for Effectiveness of the Practice

The randomized trial by Donald et al found more falls in the group housed in rooms with

carpeted flooring, although the difference barely failed to achieve statistical significance. The

earlier retrospective analysis by Healey found that the rate of injury was significantly lower for

patients who fell on carpet rather than vinyl flooring.5

 The severity of injuries was not reported

and it was not possible to determine whether the rate of falls differed according to flooring

material.

Potential for Harm

No harm was identified, although it is possible that asthmatic patients might react to

increased levels of dust-mite allergens in carpeted wards.6

Costs and Implementation

No cost estimates for changes in flooring were reported in the literature. Implementation

of this practice would require a large expenditure for facilities upgrades nationwide. Likewise,

the costs associated with keeping various floor surfaces clean in the hospital or nursing home

environment would also be high.

Comment

Advances in biomedical engineering could result in potentially significant redesign of the

physical environment in hospitals and nursing facilities. The primary aim of specialized flooring

could be either to reduce the risk of falling or to reduce the risk of an injury once a fall has

occurred, or both. The two studies analyzed seem to indicate that carpeted floors may increase

fall rates but decrease fall injuries; it is possible that other surfaces would yield better results.

Further study of this area is warranted.
295

Table 26.4. Study of special flooring for falls prevention

Study Participants and Setting Study Design,

Outcomes

Results

Donald,

20004

32 patients in an elderly care

rehabilitation ward in the

United Kingdom in 1996

Level 2,

Level 1 Rate of falls:

Carpet, 10/16 (63%); vinyl, 1/16 (6%)

RR 8.3 (95% CI: 0.95-73; p=0.05)

Healey,

19945

Random sample of accident

forms (n=213) from care of

elderly unit over 4 years

Level 3,

Level 1

Falls resulting in injury:

Carpet, 15%; vinyl, 91% (p<0.001)

* CI indicates confidence interval; RR, relative risk.

References

1. Wilmott M. The effect of a vinyl floor surface and a carpeted floor surface upon walking in

elderly hospital in-patients. Age Ageing. 1986;15:119-120.

2. Casalena JA, Badre-Alam A, Ovaert TC, Cavanagh PR, Streit DA. The Penn State safety

floor. Part II: reduction of fall-related peak impact forces on the femur. J Biomech Eng.

1998;120:527-532.

3. Stevens JA, Olson S. Reducing falls and resulting hip fractures among older women.

MMWR Morb Mortal Wkly Rep 2000; 49(RR02):1-12.

4. Donald IP, Pitt K, Armstrong E, Shuttleworth H. Preventing falls on an elderly care

rehabilitation ward. Clin Rehabil. 2000;14:178-185.

5. Healey F. Does flooring type affect risk of injury in older patients? Nurs Times.

1994;90:40-41.

6. Sadler C. Floored thinking. Nurs Times. 1993;89:20-21.

Subchapter 26.5. Hip Protectors to Prevent Hip Fracture

Background

Hip fractures are an important cause of morbidity and mortality, resulting in about

340,000 hospitalizations in 1996 in the United States for those aged 65 years and older.1

 Six

months after hospitalization for hip fracture, 12.8% of patients require total assistance to

ambulate according to a recent prospective study.2

 New dependency in physical and instrumental

activities of daily living is also considerable. For those independent prior to a hip fracture, 20%

of patients require assistance putting on pants, 66% require assistance in getting on or off the

toilet, and 90% require assistance climbing 5 stairs after a hip fracture.3

 Mortality rates range

between 18-33% within the first year post-fracture.3

 One proposed prevention measure is for a

patient to wear a protective pad around the hip to absorb the impact of a fall and to reduce the

risk of fracture by “shunting” energy away from the hip region.
296

Practice Description

External hip protectors are usually made with plastic pads or shields that are padded or

constructed with foam-type materials. They fit into specially-designed pockets in undergarments

or pants. They are designed to be worn during the day for people who are out of bed, walking or

engaged in activities that place them at higher risk for falls. Ideally, they would be worn all the

time to protect individuals from nighttime falls.

Prevalence and Severity of the Target Safety Problem

See Introduction to Chapter 26.

Opportunities for Impact

No data on the nationwide use of hip protectors in the hospital or nursing home are

available. A small minority of institutions are in the process of evaluating them, and a few may

have begun to use them.

Study Designs

Five relevant randomized controlled trials4-8 were identified from a literature search and

from a Cochrane systematic review.9

 The Cochrane review cites 2 additional abstracts10,11 not

included here. Four of the trials evaluate effectiveness of the devices and one study8

 examines

compliance rates of wearing hip protectors as part of a pilot study. Two studies were clusterrandomized and 2 were randomized by individual patient.

Study Outcomes

Studies reported hip fractures as an outcome, although compliance with the intervention

was the primary outcome in one study. Additional outcomes reported were mortality, falls, and

non-hip fractures.

Evidence for Effectiveness of the Practice

External hip protectors appear to be an effective means to reduce the risk of a hip fracture

in older persons aged 65 and over who fall. Table 26.5.1 lists the abstracted studies and outlines

their pertinent features. The generalizability of these results to wider audiences and to lower risk

populations has not been demonstrated, nor has the potential benefit for hospitalized patients

been reported. Concerns with compliance could hinder their effectiveness on a population-wide

level.

Potential for Harm

Discomfort from wearing the device, difficulty managing the garment while dealing with

continence, and the potential for skin irritation and breakdown are causes for concern if fragile

older people were to wear hip protectors. Because long-term compliance is low, it is unclear how

many people would experience such problems if the devices were worn for longer periods during

the day or for long-term use.
297

Costs and Implementation

An Australian study published in 2000 quoted a cost of A$10 per pair (approximately

$5.25US).4

 The retail price quoted by one US manufacturer of a different hip protector is

approximately $90 per pair. The lycra-containing undergarment used by some manufacturers to

keep the hip pads in place requires special laundering and would require a tracking system

similar to that used for other specialized garments or medical devices assigned to patients within

a facility. Once provided, if devices can be put on and taken off by individual users,

implementation is straightforward. The cost-effectiveness of the devices has not been formally

reported.

Comment

One of the main philosophical concerns raised by these studies is the change in emphasis

from primary prevention of the underlying cause of hip fractures (ie, falls) to an emphasis on

methods of protecting patients from the deleterious consequences of falls. However, a strategy

for addressing the multiple risk factor model for falls is still warranted for primary falls

prevention. With this caveat in mind, there is strong evidence to support the ability of hip

protectors to prevent hip fractures. This evidence, in addition to their high face validity, may

encourage their rapid adoption. Further evaluation of their costs, acceptability to patients, and

effectiveness in hospitalized patients (versus nursing home residents) is needed.
298

Table 26.5.1. Hip protectors to prevent hip fracture*

Study Participants and

Setting

Design,

Outcomes

Results

Parker,

20009

1752 nursing home or

rest home residents in

5 countries

Level 1A,

Level 1

Peto OR 0.44 (95% CI: 0.26-0.75) of hip

fracture in the intervention group in clusterrandomized studies;

Peto OR 0.22 (95% CI: 0.09-0.57) in patientrandomized studies

Chan,

20004

71 nursing home

residents in Australia,

year not stated

Level 1,

Level 1

RR of hip fracture in the intervention group

0.264 (95% CI: 0.073-0.959)

Ekman,

19925

746 nursing home

residents in Sweden,

year not stated

Level 1,

Level 1

RR of hip fracture in the intervention group

0.33 (95% CI: 0.11-1.00)

Kannus,

20006

1801 community

based elderly in

Finland, 1996-1997

Level 1,

Level 1

RR of hip fracture in the intervention group

0.4 (95% CI: 0.2-0.8; p=0.008)

Lauritzen,

19937

665 nursing home

residents in Denmark,

1991-1992

Level 1,

Level 1

RR of hip fracture in the intervention group

0.44 (95% CI: 0.21-0.94)

Villar,

19988

141 rest home

residents in the UK,

year not stated

Level 1,

Level 3

30% compliance over 3 months (hip fracture

outcomes not assessed)

* CI indicates confidence interval; OR, odds ratio; and RR, relative risk.

References

1. Stevens JA, Olson S. Reducing falls and resulting hip fractures among older women.

MMWR Morb Mortal Wkly Rep. 2000;49:1-12.

2. Hannan EL, Magaziner J, Wang JJ, et al. Mortality and locomotion 6 months after

hospitalization for hip fracture. JAMA. 2001;285:2736-2742.

3. Magaziner J, Hawkes W, Hebel JR, et al. Recovery from hip fracture in eight areas of

function. J Gerontol. Medical Sciences 2000;55A:M498-M507.

4. Chan DK, Hillier G, Coore M, et al. Effectiveness and acceptability of a newly designed

hip protector: a pilot study. Arch Gerontol Geriatr. 2000;30:25-34.

5. Ekman A, Mallmin H, Michaelsson K, Ljunghall S. External hip protectors to prevent

osteoporotic hip fractures. Lancet. 1997;350:563-564.

6. Kannus P, Parkkari J, Niemi S, et al. Prevention of hip fracture in elderly people with use

of a hip protector. N Engl J Med. 2000;343:1506-1513.
299

7. Lauritzen JB, Petersen MM, Lund B. Effect of external hip protectors on hip fractures.

Lancet 1993;341:11-13.

8. Villar MTA, Hill P, Inskip H, Thompson P, Cooper C. Will elderly rest home residents

wear hip protectors? Age Ageing. 1998;27:195-198.

9. Parker MJ, Gillespie LD, Gillespie WJ. Hip protectors for preventing hip fractures in the

elderly. In: The Cochrane Library, Issue 2, 2001. Oxford: Update Software.

10. Harada A, Okulzumi H. Hip fracture prevention trial using hip protector in Japanese

elderly. Osteoporos Int. 1998;8(Suppl 3):121.

11. Heikinheimo R, Jantti PL, Aho HJ, Maki-Jokela PL. To fall but not to break – safety pants.

Proceedings of the Third International Conference on Injury Prevention and Control,

Melborne 1996;1996:576-578.
300
301

Chapter 27. Prevention of Pressure Ulcers in Older Patients

Joseph V. Agostini, MD

Dorothy I. Baker, PhD, RNCS

Sidney T. Bogardus, Jr., MD

Yale University Schools of Medicine and Public Health

Background

Pressure ulcers, localized areas of tissue damage or necrosis that develop due to pressure

over a bony prominence, are common causes of morbidity in older hospitalized and

institutionalized persons. Other terms referring to the same phenomena are pressure sores,

bedsores, and decubitus ulcers. Risk factors include immobility, friction, shear, incontinence,

cognitive impairment and poor nutritional status.1-3 Pressure ulcers are one indicator of quality of

care measured by nursing homes as part of the mandatory Minimum Data Set (MDS), which is

required for participation in Medicare and Medicaid. Part of the MDS evaluation includes the

Resident Assessment Instrument, which serves as a guide to assess pressure ulcers and many

other pertinent clinical problems.4

Risk assessment is an integral part of prevention efforts. The Norton scale5 and the

Braden scale6

 are widely used tools to identify at-risk patients. The Norton scale assesses five

domains: activity, incontinence, mental status, mobility, and physical condition. The Braden

scale assesses six domains: activity, dietary intake, friction, mobility, sensory perception, and

skin moisture. Agreement between the scales is 0.73 using the kappa statistic.7

Different strategies have been used for primary prevention. Major clinical guidelines,8 for

pressure ulcer prevention are based primarily on published evidence, and in some areas, on

professional judgment and face validity of practices. Turning and/or repositioning patients is a

practice with high face validity, but there are no well-designed controlled trials that examine its

effect in the absence of other interventions. Other practices include regular skin inspection and

assessment, use of appropriate pressure-relief surfaces, improved mobility, adequate nutritional

intake, and documentation of the skin examination. Additionally, the use of general educational

interventions for hospital staff is supported by before-after study designs.9, 10 Several reports

suggest the value of using topical applications applied to intact skin in an attempt to prevent

ulcers.5, 11, 12 This chapter focuses on the use of pressure-relieving strategies that can be

incorporated into hospital or nursing home practice and are based on evidence from controlled

clinical trials.

Practice Description

The preventive practices that have received the most research attention are the use of

specific beds or mattresses. Many studies have compared a specific mattress with either another

high-technology mattress or with a “standard” hospital mattress. A standard mattress, which is

not uniformly defined in the literature, may be described as a hospital-issue, usually foam-based

mattress found in a typical hospital room. The lack of consensus as to what constitutes a standard

hospital mattress presents an interpretative challenge to investigators and administrators hoping

to extrapolate results of a published trial to another locale.

In 1991 Krasner reported that there were over 115 different pressure-relieving support

surfaces on the market.13 Sheepskin and other inexpensive pads (eg, “egg-crate” mattresses) are

common pressure-reducing devices. Other static devices include pressure-relieving pads (eg,
302

fabricated from elastic polymers) such as those used to cover operating room tables. Constant,

low-pressure supports maintain uniform pressure throughout. Examples include higher-grade

foam, and gel-, air-, or water-filled supports. In contrast, dynamic or alternating air devices have

a built-in pump that continually redistributes air pressure. Low air-loss beds, as their name

implies, permit small amounts of air to escape through a network of pores, whereas high air-loss

(or air-fluidized) beds purposefully pump air through ceramic-type beads. Finally, kinetic

turning beds, which allow continual rotation, are used more commonly in critically ill patients.

Prevalence and Severity of the Target Safety Problem

In 1990 a large, prospective epidemiologic study reported the one-year incidence for

pressure ulcer development in nursing homes to be 13.2%,14 with prevalence reports ranging

from 7% to 23% in a systematic review.15 Risk-adjusted rates of new pressure ulcers have been

reported to decrease by 25% from 1991 to 1996, based on a recent study using data from the

Minimum Data Set.16 In hospitalized patients, prevalence ranges from about 3% to 11%.17

Meehan reported that the prevalence of pressure ulcers was 11.1% in 177 hospitals surveyed in

1993 and that 54% of the pressure ulcers occurred in patients 70 to 89 years old.18 Eckman

estimated that almost 1.7 million hospitalized patients had pressure ulcers.19 Approimately 60%

of pressure ulcers develop in these acute care settings. The National Health and Nutrition

Examination Survey found that less than 20% of pressure ulcers arise in non-institutional

environments.20

Pressure ulcers result in both increased length of hospital stay and hospital costs21 and

increased nursing care time, as demonstrated by a study of long-term care patients.22 Cellulitis,

osteomyelitis, and sepsis are morbid complications of untreated pressure ulcers. Increased

mortality has also been associated with pressure ulcers.17

Opportunities for Impact

The passage of the Omnibus Budget Reconciliation Act of 1987 and subsequent

implementation regulations provided a written mandate for hospitalized and institutionalized

patients to receive regular assessment, preventive measures, and treatment of pressure ulcers.

There are no specific data on the current utilization of preventive measures by hospitals. The

pressure ulcer protocols often vary from institution to institution.

Study Designs

We identified a recent systematic review of pressure-relieving devices23 that evaluated 37

randomized controlled trials (RCTs), 31 of which were focused on pressure ulcer prevention

(Table 27.1). Seven trials compared standard foam mattresses with various “low-technology”

supports. These low-technology supports were defined as beds with constant low-pressure

supports, including bead-, water-, or gel-filled supports; static air-filled supports; or foam or

Silicore-filled supports. Seven of the trials compared constant low-pressure devices with

alternating pressure devices. Six studies limited enrollment to orthopedic patients, 5 to patients

in intensive care units, and 3 to patients undergoing operations (ie, the study evaluated different

operating table surfaces). We identified no further RCTs of pressure ulcer prevention published

after the systematic review identified above.

Study Outcomes

All studies reported pressure ulcer development in both intervention and control groups.

Pressure ulcer grading systems were used in most trials. Typically, a 4-level grading system was
303

employed, ranging from Grade 1 (discolored skin) to Grade 4 (full-thickness skin lesions with

bone involvement).

Evidence for Effectiveness of the Practice

Many specialized beds appear to be effective in reducing the development of pressure

ulcers when compared with standard mattresses. For example, in 4 studies24-27 cited by the

systematic review23 that compared standard hospital foam mattresses to enhanced foam

alternatives, a summary relative risk of 0.29 (95% CI: 0.19-0.43) was calculated, favoring the

intervention group. Between-group comparisons of the previously defined low-technology

constant low-pressure devices did not yield clear conclusions. Similarly, in 7 RCTs the

comparison of alternating pressure devices with a variety of constant low-pressure devices (a

water mattress, foam pad, static air mattress, and foam overlays) showed no significant

difference in pressure ulcer development (summary RR 0.84, 95% CI: 0.57-1.23).23 However, a

study of alternating pressure supports compared with standard foam mattresses did demonstrate

lower pressure ulcer development in the intervention group (RR 0.32; 95% CI 0.14-0.74).28

Comparing pressure-reducing devices among themselves (versus against a standard mattress)

yields no significant differences in the prevention of pressure ulcers. These trials have been

summarized in a recent review.29

In addition, 2 published trials evaluating different operating table-like surfaces suggest

reduction in pressure ulcer development with enhanced surfaces.30, 31 In a well-designed RCT of

446 patients, Nixon and colleagues31 showed that a dry gel-polymer pad placed on an operating

table decreased the incidence of new pressure ulcers by almost half—11% for intervention

patients vs. 20% for control patients placed on a standard operating table mattress (RR 0.46, 95%

CI: 0.26-0.82).

Several caveats temper the interpretation of studies of specialized pressure-relieving

surfaces. In general the studies had poor methodologic design, as the systematic review points

out.23 The trials were mostly small, true baseline comparability was hard to confirm,

standardization of protocols was often unclear, and assessments were frequently unblinded.

Patient selection across trials was not consistent, and differences in pressure ulcer risk at

enrollment were difficult to compare across studies.

Potential for Harm

None reported.

Costs and Implementation

The costs of treating a pressure ulcer are estimated to range from $4000 to $40,000 for

newly developed ulcers.32 Indeed, both hospital costs and length of stay are significantly higher

for patients who develop pressure ulcers during hospitalization, as noted earlier.21 In the nursing

home in particular, failure to prevent this adverse outcome carries increasing liability—the

median settlement for pressure ulcer-related disputes was $250,000 between the years 1977 and

1987.33 The cost of specialized beds and mattresses to prevent pressure ulcer development can be

high, ranging from $40 to $85 per day for low air-loss beds.34 Specialized beds and intensive

nursing interventions all carry clear resource implications. Inman and colleagues35 have

demonstrated the cost-effectiveness of an air suspension bed compared to a standard intensive

care unit bed. Yet cost-effectiveness studies of the many different pressure-relieving devices

have not been formally completed.
304

In terms of the feasibility of implementing these specific devices and following

guidelines for high-risk patients, both cost and time considerations must be examined.36 Other

considerations relate to the design and functionality of a particular bed or mattress—for example

the ability of nursing staff to move and transfer patients placed on deeper or bulkier beds.

Finally, difficulty in accurately assessing changes in the incidence and prevalence of pressure

ulcers resulting from the institution of preventive measures is another barrier to documenting

progress.37

Comment

Overall there is adequate evidence that specially designed surfaces effectively prevent the

development of pressure ulcers in high-risk patients, but the definition of high risk varies across

studies. The variety of pressure-relieving devices makes it difficult to recommend one over

another because there are few direct comparisons among the many different types of surfaces. Of

note, the treatment of established pressure ulcers is a separate topic, and the type of pressurerelieving surface that is effective in treatment may not prove best for prevention. Appropriate

patient selection criteria need further development and refinement because the cost of many

prevention interventions is high. The necessity for larger RCTs to assess both clinical and costeffectiveness of these specially designed mattresses is clear. Better descriptions of what

constitutes a “standard” bed or mattress, and improved reporting of baseline comparability

between experimental and control groups are also necessary to adequately interpret existing

studies. To better track progress in prevention, standardized strategies should be developed so

that accurate prevalence estimates can be documented.

Table 27.1. Studies of pressure ulcer prevention*

Participants and Setting Study Design,

Outcomes

Relative Risk of Pressure Ulcer

Systematic review of 31 RCTs from

the US, UK and elsewhere assessing

pressure relieving interventions for

prevention of pressure ulcers23

Level 1A,

Level 1

Enhanced alternative foam mattresses

vs. standard hospital mattresses:

RR 0.29 (95% CI: 0.19-0.43)

Alternating pressure vs. constant low

pressure devices: RR 0.84

(95% CI: 0.57-1.23)

* CI indicates confidence interval; RCT, randomized controlled trial; and RR, relative risk.

References

1. Berlowitz DR, Wilking SV. Risk factors for pressure sores. A comparison of crosssectional and cohort-derived data. J Am Geriatr Soc. 1989;37:1043-1050.

2. Brandeis GH, Ooi WL, Hossain M, Morris JN, Lipsitz LA. A longitudinal study of risk

factors associated with the formation of pressure ulcers in nursing homes. J Am Geriatr

Soc. 1994;42:388-393.

3. Allman RM, Goode PS, Patrick MM, Burst N, Bartolucci AA. Pressure ulcer risk factors

among hospitalized patients with activity limitation. JAMA. 1995;273:865-870.

4. Long term care facility resident assessment (RAI) user's manual. Version 2.0. Baltimore,

MD: Health Care Financing Administration; 1995.
305

5. Norton D, McLaren R, Exton-Smith AN. An investigation of geriatric nursing problems in

hospital. London: Churchill Livingstone; 1962.

6. Bergstrom N, Braden BJ, Laguzza A, Holman V. The Braden Scale for Predicting Pressure

Sore Risk. Nurs Res. 1987;36:205-210.

7. Xakellis GC, Frantz RA, Arteaga M, Nguyen M, Lewis A. A comparison of patient risk for

pressure ulcer development with nursing use of preventive interventions. J Am Geriatr Soc.

1992;40:1250-1254.

8. Agency for Health Care Policy and Research. Pressure Ulcer in Adults: Prediction and

Prevention. Clinical Practice Guideline, Number 3. Rockville, MD: Public Health Service,

U.S. Department of Health and Human Services; 1992.

9. Blom MF. Dramatic decrease in decubitus ulcers. Geriatr Nurs. 1985;6:84-87.

10. Moody BL, Fanale JE, Thompson M, Vaillancourt D, Symonds G, Bonasoro C. Impact of

staff education on pressure sore development in elderly hospitalized patients. Arch Intern

Med. 1988;148:2241-2243.

11. van der Cammen TJ, O'Callaghan U, Whitefield M. Prevention of pressure sores. A

comparison of new and old pressure sore treatments. Br J Clin Pract 1987;41:1009-1011.

12. Declair V. The usefulness of topical application of essential fatty acids (EFA) to prevent

pressure ulcers. Ostomy Wound Management. 1997;43:48-52,54.

13. Krasner D. Patient support surfaces. Ostomy Wound Management. 1991;33:47-56.

14. Brandeis GH, Morris JN, Nash DJ, Lipsitz LA. The epidemiology and natural history of

pressure ulcers in elderly nursing home residents. JAMA. 1990;264:2905-2909.

15. Smith DM. Pressure ulcers in the nursing home. Ann Intern Med. 1995;123:433-442.

16. Berlowitz DR, Bezerra HQ, Brandeis GH, Kader B, Anderson JJ. Are we improving the

quality of nursing home care: the case of pressure ulcers. J Am Geriatr Soc. 2000;48:59-62.

17. Allman RM, Laprade CA, Noel LB, Walker JM, Moorer CA, Dear MR, et al. Pressure

sores among hospitalized patients. Ann Intern Med. 1986;105:337-342.

18. Meehan M. National pressure ulcer prevalence survey. Adv Wound Care. 1994;7:27-

30,34,36-8.

19. Eckman KL. The prevalence of dermal ulcers among persons in the U.S. who have died.

Decubitus. 1989;2:36-40.

20. Guralnik JM, Harris TB, White LR, Cornoni-Huntley JC. Occurrence and predictors of

pressure sores in the National Health and Nutrition Examination survey follow-up. J Am

Geriatr Soc. 1988;36:807-812.

21. Allman RM, Goode PS, Burst N, Bartolucci AA, Thomas DR. Pressure ulcers, hospital

complications, and disease severity: impact on hospital costs and length of stay. Adv

Wound Care. 1999;12:22-30.

22. D'Hoore W, Guisset AL, Tilquin C. Increased nursing time requirements due to pressure

sores in long-term-care residents in Quebec. Clin Perform Qual Health Care. 1997;5:189-

194.

23. Cullum N, Deeks J, Sheldon TA, Song F, Fletcher AW. Beds, mattresses and cushions for

pressure sore prevention and treatment. In: The Cochrane Library, Issue 4, 2000. Oxford:

Update Software.

24. Hofman A, Geelkerken RH, Wille J, Hamming JJ, Hermans J, Breslau PJ. Pressure sores

and pressure-decreasing mattresses: controlled clinical trial. Lancet. 1994;343:568-571.

25. Santy JE, Butler MK, Whyman JD. A comparison study of 6 types of hospital mattress to

determine which most effectively reduces the incidence of pressure sores in elderly patients
306

with hip fractures in a District General Hospital. Report to Northern & Yorkshire Regional

Health Authority 1994.

26. Gray DG, Campbell M. A randomized clinical trial of two types of foam mattresses. J

Tissue Viability. 1994;4:128-132.

27. Collier ME. Pressure-reducing mattresses. J Wound Care. 1996;5:207-211.

28. Andersen KE, Jensen O, Kvorning SA, Bach E. Decubitus prophylaxis: a prospective trial

on the efficiency of alternating-pressure air-mattresses and water-mattresses. Acta Derm

Venereol (Stockholm). 1982;63:227-230.

29. Thomas DR. Issues and dilemmas in the prevention and treatment of pressure ulcers: a

review. J Gerontol. 2001;56A:M328-M40.

30. Aronovitch SA. A comparative, randomized, controlled study to determine safety and

efficacy of preventive pressure ulcer systems: preliminary analysis. Adv Wound Care.

1998;11:15-16.

31. Nixon J, McElvenny D, Mason S, Brown J, Bond S. A sequential randomised controlled

trial comparing a dry visco-elastic polymer pad and standard operating table mattress in the

prevention of post-operative pressure sores. Int J Nurs Stud. 1998;35:193-203.

32. Hibbs P. The economics of pressure ulcer prevention. Decubitus. 1988;1:32-38.

33. Bennett RG, O'Sullivan J, DeVito EM, Remsburg R. The increasing medical malpractice

risk related to pressure ulcers in the United States. J Am Geriatr Soc. 2000;48:73-81.

34. Ferrell BA, Keeler E, Siu AL, Ahn S, Osterweil D. Cost-effectiveness of low-air-loss beds

for treatment of pressure ulcers. J Gerontol. 1995;50A:M141-M46.

35. Inman KJ, Sibbald WJ, Rutledge FS, Clark BJ. Clinical utility and cost-effectiveness of an

air suspension bed in the prevention of pressure ulcers. JAMA. 1993;269:1139-1143.

36. Hu TW, Stotts NA, Fogarty TE, Bergstrom N. Cost analysis for guideline implementation

in prevention and early treatment of pressure ulcers. Decubitus. 1993;6:42-46.

37. Smith DM, Winsemius DK, Besdine RW. Pressure sores in the elderly: can this outcome

be improved? J Gen Intern Med. 1991;6:81-93.
307

Chapter 28. Prevention of Delirium in Older Hospitalized Patients

Joseph V. Agostini, MD

Dorothy I. Baker, PhD, RNCS

Sharon K. Inouye, MD, MPH

Sidney T. Bogardus, Jr., MD

Yale University Schools of Medicine and Public Health

Background

Delirium, or acute confusional state, is a common complication among hospitalized older

patients. Delirium is characterized by a sudden onset and fluctuating course, inattention, altered

level of consciousness, disorganized thought and speech, disorientation, and often behavioral

disturbance. As with other common geriatric syndromes, the etiology of delirium is

multifactorial. Previous research has identified a broad range of predisposing and precipitating

factors.1-4 These include older age, cognitive or sensory impairments, dehydration, specific

medication usage (eg, psychoactive drugs), concurrent medical illness, and sleep deprivation.

The multifactorial nature of delirium suggests that intervention strategies targeting multiple

known risk factors might be effective in preventing its occurrence in hospitalized older patients.

In this chapter, we review multicomponent prevention programs that can be applied to a general

hospitalized patient population, not restricted to one admitting diagnosis (in keeping with the

crosscutting patient safety focus of the Report; Chapter 1). For example, a study comparing the

effect of postoperative analgesia using intravenous versus epidural infusions after bilateral knee

replacement surgery was not included.5

Practice Description

A number of individual interventions have been used in efforts to prevent delirium. Some

could be considered part of general nursing practice, whereas others involve medical

assessments by physicians or consultants. General strategies to prevent delirium include use of

patient reorientation techniques (such as verbal reassurance, re-introduction of team members,

review of the daily hospital routine and patient schedule), environmental modifications (visible

clocks and calendars), and scheduled patient mobility. The number and complexity of these

interventions can vary, with individual nursing discretion usually determining how and when

these interventions are implemented. Patient education,6

 nursing staff education,7 and family

involvement8

 are also useful. Approaches for primary prevention that incorporate physician

consultants or geriatric consultative teams9-11 are reviewed elsewhere in this Report (see

Chapters 29 and 30).

Formal prevention programs target defined risk factors by implementing multiple

practices according to standardized protocols. For example, a recently reported, multicomponent

strategy focused on 6 risk factors and successfully developed intervention protocols to address

each of them.12 Patients with cognitive impairment received daily orientation interventions and

3-times daily cognitive stimulation activities. To target sleep impairment, patients received nonpharmacologic sleeping aids (eg, back massage and relaxation tapes), while hospital staff

engaged in noise-reduction strategies such as setting beepers to vibrate and using silent pill

crushers. Immobility was addressed with a 3-times daily exercise protocol adapted for use with

bed-bound and ambulatory patients. Sensory impairments were addressed by providing devices

such as auditory amplifiers, visual aids, and larger size push-button phones. Patients with
308

evidence of dehydration received standardized repletion interventions. A geriatric nurse

specialist and staff assisted by trained volunteers carried out all the interventions.

Prevalence and Severity of the Target Safety Problem

The target safety problem is the primary prevention of delirium, rather than the

treatment13 of existing delirium. In the United States, delirium affects an estimated 2.3 million

hospitalized elders annually, accounting for 17.5 million inpatient days, and leading to more than

$4 billion in Medicare costs (1994 dollars).12 Studies have found that delirium in hospitalized

patients contributes to longer lengths of stay,14 increased mortality,15-17 and increased rates of

institutional placement.18, 19 New cases of delirium occur in approximately 15% to 60% of

hospitalized older patients, depending on the number of risk factors present at

admission.4,15,18,20,21 Moreover, because many cases of delirium go unrecognized during

hospitalization and because symptoms may persist for months after discharge,22 these may be

conservative estimates. Safety practices to reduce delirium may thus have substantial impact on

the health and well-being of older patients in hospitals. These practices may also impact nursing

home residents and other institutionalized patients, but our practice review did not identify any

studies carried out among these patient populations.

Opportunities for Impact

It is difficult to estimate the extent of existing practices aimed at decreasing delirium. A

comprehensive model, the Hospital Elder Life Program,23 which incorporates the delirium

interventions reviewed in one study in this chapter,12 is presently in the initial dissemination

phase at 6 replication sites, with 16 hospitals on a waiting list. Present evidence suggests that few

facilities currently have intervention programs designed for the primary prevention of delirium.

The opportunity for impact in nursing homes and other long-term care facilities is great, but thus

far studies have not targeted these settings.

Study Designs

Cole24 conducted a structured search of the medical literature and identified 10

intervention trials to prevent delirium in hospitalized patients. Of these, we excluded one study

of much younger patients (mean age, 49 years)25 and one study that incorporated interventions

not applicable to most hospitalized elders (eg, early surgery, prevention and treatment of perioperative blood pressure falls).26 Three used psychiatric consultations27-29 which did not fit our

criteria for risk factor intervention (see Chapter 29 for similar studies). Table 28.1 lists the

remaining 5 studies6, 8, 30-32 and a later study,12 which is the largest controlled trial to date.

Study Outcomes

All of the studies in Table 28.1 reported delirium or confusion symptoms as an outcome

measure. Each study, however, used a different instrument to identify delirium: DSM-III,33 the

Confusion Assessment Method,34 the Short Portable Mental Status Questionnaire,35 or a scoring

system based on delirium symptoms.

Evidence for Effectiveness of the Practice

The earliest studies, by Owens6

 and Chatham,8 focused on the effects of patient and

family education, respectively. Delirium symptoms modestly improved but achieved statistical

significance in only 5 of the 11 symptom categories reported in the latter study. Both studies

were limited by small numbers of patients, non-standardized interventions, and minimal data on
309

baseline co-morbidities of the enrolled patients. The study by Williams and colleagues,32 which

targeted a population at high risk for delirium (older patients with hip fracture), also

demonstrated a statistically significant reduction in delirium symptoms by targeting

environmental nursing interventions and patient education. Two subsequent studies did not show

a reduction in delirium. The low incidence of delirium (only 3 cases in 30 intervention patients)

in the study by Nagley et al30 created inadequate power to detect a significant effect with only 60

total patients. Although a high percentage of patients experienced delirium in the study by

Wanich et al,31 79% of cases were diagnosed at the time of admission (prevalent rather than

incident cases) and therefore could not have been prevented by the intervention. Both of these

studies may also have suffered from contamination bias. The greatest benefit in delirium

prevention, a 40% risk reduction, occurred in the study by Inouye et al,12 a carefully designed

and implemented hospital program targeting 6 well-recognized risk factors for delirium, in

which adherence to each intervention protocol was tracked. The intervention reduced the number

and severity of patients’ risk factors and was successful in preventing patients’ first delirium

episode.

Potential for Harm

None noted.

Costs of Implementation

The only recent estimate of cost per case of delirium prevented was $6341 in a delirium

prevention trial,12 which is less than the cost associated with prevention of other hospital

complications such as falls. A further analysis of the same patients reveals that the

multicomponent strategy is cost-effective for those at intermediate risk of delirium, but not for

those at highest risk.36

Comment

The literature for delirium prevention studies is small, and the methodologic quality of

many studies is poor. However, one high quality study12 has demonstrated that multicomponent

interventions can prevent incident delirium in hospitalized patients. The interventions have high

face validity and are both feasible and transportable across institutions and hospital units,

suggesting that implementation in different practice settings would be practical. Implementing a

multicomponent intervention on a hospital-wide basis throughout the United States would

require significant commitment from hospital staff. Programs such as the Hospital Elder Life

Program23 can be readily integrated into hospital practice and have been successful in preventing

both cognitive and functional decline using targeted, practical interventions. Others of these

practices could be incorporated by either support staff or trained volunteers, which may save

resources and underscore the fact that many common sense interventions do not require a larger

professional staff. Future studies should focus on refining the most effective multifactorial

programs, determining the optimal combination of interventions, defining appropriate target

populations based on delirium risk, demonstrating effectiveness across multiple clinical sites,

and disseminating the most cost-effective practices.
310

Table 28.1. Six studies of delirium prevention*

Study Study Setting Interventions Study Design

Outcomes

Results†

Chatham,

19788

20 surgical

patients in a

university

affiliated

hospital, 1977

• Family education

• Patient education

Level 2,

Level 1

Delirium symptoms rate:

intervention resulted in

improvement in 5 of 11

areas—orientation,

appropriateness, confusion,

delusions, and sleep (p<0.05

for each)

Inouye,

199912

852 patients in a

university

hospital, 1995-

1998

Targeted 6 risk factors:

• Cognitive impairment

• Immobility

• Visual impairment

• Hearing impairment

• Dehydration

• Sleep deprivation

Level 2,

Level 1

Delirium rate: intervention 9.9%,

control 15.0% (matched OR

0.60, 95% CI: 0.39-0.92);

Episodes of delirium:

intervention 62, control 90

(p=0.03);

Total days with delirium:

intervention 105, control

161 (p=0.02)

Nagley,

198630

60 patients at a

university

affiliated

hospital

16 interventions, including:

• Orientation strategies

• Providing sensory aides

• Ambulation

• Hydration measures

• Nursing interaction

Level 2,

Level 1

No significant difference in

mental status scores between

groups (p>0.05)

Owens,

19826

64 surgical

patients in a

university

hospital

• Patient education Level 2,

Level 1

Delirium symptoms rate:

intervention 59%, control

78% (p>0.05)

Wanich,

199231

235 patients in a

university

hospital, 1986-

1987

• Nursing education

• Caregiver education

• Orientation strategies

• Mobilization

• Environmental

modifications

• Medication evaluation

Level 2,

Level 1

Delirium rate: intervention

19%, control 22% (p=0.61)

Williams,

198532

227 orthopedic

patients in 4

hospitals

• Patient education

• Orientation strategies

• Providing sensory aides

Level 2,

Level 1

Delirium symptoms rate:

intervention 43.9%, control

51.5% (p<0.05)

* CI indicates confidence interval; OR, odds ratio.

† Delirium rate is the percentage of patients with one or more episodes of delirium.
311

References

1. Elie M, Cole MG, Primeau FJ, Bellavance F. Delirium risk factors in elderly hospitalized

patients. J Gen Intern Med. 1998;13:204-212.

2. Inouye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti ME. A predictive model for

delirium in hospitalized elderly medical patients based on admission characteristics. Ann

Intern Med. 1993;119:474-481.

3. Schor JD, Levkoff SE, Lipsitz LA, Reilly CH, Cleary PD, Rowe JW, et al. Risk factors for

delirium in hospitalized elderly. JAMA. 1992;267:827-831.

4. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly

persons. Predictive model and interrelationship with baseline vulnerability. JAMA.

1996;275:852-857.

5. Williams-Russo P, Urquhart BL, Sharrock NE, Charlson ME. Post-operative delirium:

predictors and prognosis in elderly orthopedic patients. J Am Geriatr Soc. 1992;40:759-

767.

6. Owens JF, Hutelmyer CM. The effect of preoperative intervention on delirium in cardiac

surgical patients. Nurs Res. 1982;31:60-62.

7. Rapp CG, Onega LL, Tripp-Reimer T, Mobily P, Wakefield B, Kundrat M, et al. Unitbased acute confusion resource nurse: an educational program to train staff nurses.

Gerontologist. 1998;38:628-632.

8. Chatham MA. The effect of family involvement on patients' manifestations of

postcardiotomy psychosis. Heart Lung. 1978;7:995-999.

9. Hogan DB, Fox RA, Gadley BW, Mann OE. Effect of a geriatric consultation service on

management of patients in an acute care hospital. CMAJ. 1987;136:713-717.

10. Cole MG, Fenton FR, Englesmann F, Mansouri I. Effectiveness of geriatric psychiatry

consultation in an acute care hospital: a randomized clinical trial. J Am Geriatr Soc.

1991;39:1183-1188.

11. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip

fracture: a randomized trial. J Am Geriatr Soc. 2001;49:In press.

12. Inouye SK, Bogardus ST, Jr., Charpentier PA, Leo-Summers L, Acampora D, Holford TR,

et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N

Engl J Med. 1999;340:669-676.

13. Meagher DJ. Delirium: optimising management. BMJ. 2001; 322:144-149.

14. Pompei P, Foreman M, Rudberg MA, Inouye SK, Braund V, Cassel CK. Delirium in

hospitalized older persons: outcomes and predictors. J Am Geriatr Soc. 1994;42:809-815.

15. Cameron DJ, Thomas RI, Mulvihill M, Bronheim H. Delirium: a test of the Diagnostic and

Statistical Manual III criteria on medical inpatients. J Am Geriatr Soc. 1987;35:1007-1010.

16. Weddington WW. The mortality of delirium: an underappreciated problem?

Psychosomatics. 1982;23:1232-1235.

17. Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ.

1993;149:41-46.

18. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly.

JAMA. 1990;263:1097-1101.

19. Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to

poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998;13:234-

242.
312

20. Foreman MD. Confusion in the hospitalized elderly: incidence, onset, and associated

factors. Res Nurs Health. 1989;12:21-29.

21. Rockwood K. Acute confusion in elderly medical patients. J Am Geriatr Soc. 1989;37:150-

154.

22. Levkoff SE, Evans DA, Liptzin B, Cleary PD, Lipsitz LA, Wetle TT, et al. Delirium. The

occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern

Med. 1992;152:334-340.

23. Inouye SK, Bogardus ST, Jr., Baker DI, Leo-Summers L, Cooney LM, Jr. The Hospital

Elder Life Program: a model of care to prevent cognitive and functional decline in older

hospitalized patients. J Am Geriatr Soc. 2000;48:1697-1706.

24. Cole MG, Primeau F, McCusker J. Effectiveness of interventions to prevent delirium in

hospitalized patients: a systematic review. CMAJ. 1996;155:1263-1268.

25. Budd S, Brown W. Effect of a reorientation technique on postcardiotomy delirium. Nurs

Res. 1974;23:341-348.

26. Gustafson Y, Brannstrom B, Berggren D, Ragnarsson JI, Sigaard J, Bucht G, et al. A

geriatric-anesthesiologic program to reduce acute confusional states in elderly patients

treated for femoral neck fractures. J Am Geriatr Soc. 1991;39:6556-62.

27. Layne OL, Jr., Yudofsky SC. Postoperative psychosis in cardiotomy patients. The role of

organic and psychiatric factors. N Engl J Med. 1971;284:518-520.

28. Schindler BA, Shook J, Schwartz GM. Beneficial effects of psychiatric intervention on

recovery after coronary artery bypass graft surgery. Gen Hosp Psychistry. 1989;11:358-

364.

29. Lazarus HR, Hagens JH. Prevention of psychosis following open-heart surgery. Am J

Psychiatry. 1968;124:1190-1195.

30. Nagley SJ. Predicting and preventing confusion in your patients. J Gerontol Nurs.

1986;12:27-31.

31. Wanich CK, Sullivan-Marx EM, Gottlieb GL, Johnson JC. Functional status outcomes of a

nursing intervention in hospitalized elderly. Image J Nurs Sch. 1992;24:201-207.

32. Williams MA, Campbell EB, Raynor WJ, Mlynarczyk SM, Ward SE. Reducing acute

confusional states in elderly patients with hip fractures. Res Nurs Health. 1985;8:329-337.

33. American Psychiatric Association. Diagnostic and statistical manual of mental disorders

(3rd edition). ed. Washington, DC: American Psychiatric Press; 1980.

34. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying

confusion: the confusion assessment method. A new method for detection of delirium. Ann

Intern Med. 1990;113:941-948.

35. Pfeiffer E. A short portable mental status questionnaire for assessment of organic brain

deficit in elderly patients. J Am Geriatr Soc. 1979;23:433-438.

36. Rizzo JA, Bogardus ST, Jr., Leo-Summers L, Williams CS, Acampora D, Inouye SK. A

multicomponent targeted intervention to prevent delirium in hospitalized older patients:

what is the economic value? Medical Care. 2001;In press.
313

Chapter 29. Multidisciplinary Geriatric Consultation Services

Joseph V. Agostini, MD

Dorothy I. Baker, PhD, RNCS

Sharon K. Inouye, MD, MPH

Sidney T. Bogardus, Jr., MD

Yale University Schools of Medicine and Public Health

Background

Multidisciplinary geriatric consultation teams provide comprehensive assessment of

physical, emotional, and functional status in older persons and make recommendations regarding

prevention and management of common geriatric syndromes, functional impairments, and other

problems. Teams vary in composition but usually include a geriatrician, nurse, social worker and

other health professionals such as rehabilitative therapists, psychologists, and dieticians. Their

expertise may improve the safety of hospitalized elders (or nursing home residents) by reducing

hospital-acquired complications such as falls, delirium, functional decline, and “preventable”

deaths. Consultation teams and inpatient geriatric evaluation and management (GEM) units share

this multidisciplinary approach but differ in who controls the implementation of

recommendations. A patient’s primary physician decides whether to implement a consultation

team’s recommendations, whereas geriatric teams have direct control over implementation in

GEM units. As this difference may impact effectiveness, GEM units are reviewed separately

(Chapter 30). Multidisciplinary consultation services are available to elders living in the

community, however this chapter reviews the evidence for geriatric consultation improving the

safety of hospitalized patients or nursing home residents.

Practice Description

The structure of consultation teams, the types of evaluations they routinely perform, and

the recommendations they make vary from institution to institution. A review of published

studies reveals some common features. A team has at least one physician, a nurse practitioner or

similarly professionally-trained provider, rehabilitative experts, and usually a social worker.

Assessments typically include measures of mobility and functional status, mental status

examinations, psychological screening, evaluation of common geriatric problems (eg, risk for

falls, incontinence, and polypharmacy), and plans for rehabilitation and/or appropriate placement

at the time of discharge. The team notes its recommendations in the hospital chart,

communicates them to the physician directing care for the patient, and provides follow-up until

the patient is discharged.

Prevalence and Severity of the Target Safety Problem

Patients aged 65 years and older account for almost half of inpatient hospitalization

days.1 In 1996, they comprised 13% of the population yet accounted for 38% of the

approximately 31 million discharges from non-government, acute care hospitals.2

 The actual

target population is smaller because, although all hospitalized elders are at risk for

complications, some patients are unlikely to benefit from multidisciplinary geriatric consultation.

Strategies to target geriatric services to those patients most likely to benefit have been reviewed

in the literature.3

 The characteristics associated with potential benefit include advanced age (eg,

over 75 years old), specific geriatric conditions (eg, falls or confusion), functional impairments
314

(eg, limitations in bathing, feeding, or transferring), and psychosocial impairments (depression

or living alone).

As a patient safety practice, consultations may decrease the occurrence of iatrogenic

complications such as functional decline related to hospitalization, delirium, and falls. Functional

decline occurs in 25 to 60% of older persons after entering acute care, due to the interaction of a

patient’s existing co-morbidities with the hospital environment.4

 It results in worsened cognitive

status and physical functioning due to the stressors of hospitalization (bedrest and immobility,

medical procedures and pharmacotherapy, and the hospital environment) in older patients. For

information on the prevalence and severity of falls and delirium, see Chapters 26 and 28,

respectively.

Mortality is another important clinical outcome that may be affected. The number of

deaths that might be prevented by implementation of this practice is unknown, although the most

common medical diagnoses of patients enrolled in these consultation studies (cardiac,

pulmonary, and gastrointestinal disorders) reflect the prevalent admitting medical diagnoses for

all older patients. The in-hospital, all-cause mortality in the reviewed studies (approximately 5 to

15%) provides a context against which one can consider the potential for improvement if these

practices influence mortality.

Opportunities for Impact

The number of hospitals with multidisciplinary geriatric consultation services is not

reported in the literature. However, data from the American Hospital Association5

 indicate that

fewer than half of hospitals offer comprehensive geriatric assessment.* Researchers in the field

believe that even in those hospitals with consultation services, only a minority of the patients

most likely to benefit are being referred. Thus, if the practice is effective, there is substantial

opportunity for improvement by increasing its utilization in this vulnerable patient population.

Study Designs

A structured literature search identified 14 controlled trials: 12 randomized,6-17 1

alternate-allocation,18 and 1 prospective cohort study19 (see Table 29.1). Four of the 14 articles

report different outcome measures from the same clinical trial.6-9 One study focuses on nursing

home residents;14 all other studies were of hospitalized patients. Three of the studies were

performed in Canada and one in the United Kingdom.16-19 Two trials were limited to elderly

patients with hip fractures.15, 17 In the study by Fretwell et al, patients were admitted to a medical

ward designated for seniors and staffed with specially trained nurses.13 Because the team still

functioned in a consultative role and could not implement its own recommendations, the study is

included here rather in the chapter on GEM units (Chapter 30).

 

* Of the 4953 acute medical/surgical hospitals in the American Hospital Association (AHA)

database, 4398 (89%) responded to the AHA 1999 Annual Survey. Of responding hospitals,

1823 (41%) indicated availability of “geriatric services,” which was defined as providing one or

more of the following: comprehensive geriatric assessment, adult day care, Alzheimer’s

diagnostic-assessment services, geriatric acute care units, and/or geriatric clinics. A

conservative, upper-limit estimate assuming all 555 non-responding hospitals have “geriatric

services” would be 48%. As the survey does not ask the availability of each type of geriatric

service, the percentage of hospitals offering inpatient comprehensive geriatric assessment based

on the AHA Survey data can only be described as “less than 48%” (how much less is unknown).
315

Study Outcomes

Ten studies reported functional status outcomes, measured by the Katz20 or Lawton21

index of activities of daily living, or the Barthel Index.22 Marcantonio et al15 measured the

occurrence and severity of delirium defined according to the Confusion Assessment Method

criteria.23 Ray and colleagues reported the proportion of recurrent fallers and the rate of injurious

falls in nursing home patients during one year.14 Becker et al measured 6 classes of hospitalacquired complications: medication-related, procedures, infections, trauma or injury (eg, falls

and pressure sores), psychiatric, and other (eg, urinary retention, fecal impaction).7

 Eight trials

reported all-cause mortality in-hospital, at 6 months, or at one year.8,10-13,16,18,19 A recent metaanalysis24 incorporated unpublished mortality data from several other studies6,17 reviewed here.

Other clinically relevant outcomes were changes in pharmacotherapy prescribed, length of

hospital stay, and discharge location.

Evidence for Effectiveness of the Practice

Two non-blinded trials showed a statistically significant improvement in patients’

functional ability.17,18 Kennie et al targeted a population at high risk for functional decline during

hospitalization: elderly women with hip fractures.17 In the study by Hogan et al,18 the difference

was significant at one year but not at 3 or 6 months, suggesting that the intervention group’s

post-discharge follow-up by a geriatric team may have accounted for the difference rather than

prevention of iatrogenic functional decline in-hospital. The study by Thomas and colleagues12

showed a trend towards improved functional status. No other study reported improved functional

outcomes.

The trial by Becker et al7

 showed no significant difference in the incidence of hospitalacquired complications between intervention and control groups. Two studies that targeted

specific high-risk populations did show benefit.14,15 In the study by Marcantonio et al, a

multidisciplinary consultation including assessment and targeted recommendations per a

structured protocol in 10 domains (including pain treatment, bowel/bladder function, nutrition,

pain treatment, mobility, and environmental stimuli) resulted in a significant decrease in

perioperative delirium in patients with hip fracture.15 Ray et al enrolled nursing home residents

65+ years of age who had fallen in the previous year and had a possible problem in at least one

of 4 safety domains: environmental safety, wheelchair use, psychotropic drug use, or mobility.14

Patients who received care from the consultation team, including structured assessments and

specific recommendations in these safety domains, experienced a significant reduction in the rate

of recurrent falls (43.8% intervention group vs. 54.1% control group, p=0.03).14

The reported randomized clinical trials yielded mixed results for the outcome of all-cause

mortality, with most studies demonstrating no benefit. The study by Thomas12 reported a

statistically significant improvement in mortality at 6 months, but Gayton et al19 reported only a

trend toward improvement at 6 months. Neither of Hogan’s studies found in-hospital mortality

benefits. One study16 showed improved mortality at 4 months and one18 at 6 months but these

benefits were not sustained at one year. Hospital-acquired complications would be expected to

reduce in-hospital or short-term mortality, so the survival benefit observed many months after

hospitalization in these studies suggests that other carry-over effects (eg, improved medication

regimens) or better post-discharge care may be influencing these results. According to a metaanalysis24 the summary odds ratio for 6-month mortality in 8 of the studies cited6,10,12,13,16-19 was

0.77 (95% CI: 0.62-0.96), but the effect on 12-month mortality was not statistically significant.

The authors tested for heterogeneity of outcomes before pooling results of the trials (p=0.07). Of
316

note, the large trial (n=2353) by Reuben et al11 was not eligible for inclusion in the meta-analysis

because it was published later. Because it was larger than all other studies combined, its effect on

the pooled estimate of 6-month mortality would be to reduce any statistically significant

differences between intervention and study groups, since no survival advantage was reported at

up to one year in the study (p=0.89 for survival curve).

Potential for Harm

No harm attributable to the geriatric consultation was reported in the trials.

Costs and Implementation

Implementation of the multidisciplinary team entails logistic planning to determine the

number and type of consultative team members, and human resource coordination regarding

time allocation and staffing. Few studies included data on costs of the practice, such as hospital

costs incurred by assembly of the consultation team. Fretwell and colleagues,13 however, have

reported hospital charges in their study of 436 patients in a university-affiliated hospital. The

percentage of patients exceeding DRG reimbursement for hospitalization was similar in both

intervention and control groups, 69.7% and 71.2%, respectively. Winograd25 reported that the

cost of screening about 1200 patients to identify suitable candidates for consultation (using

predefined criteria discussed in the paper) could be accomplished by employing a trained

employee working one-quarter time, at a cost (in 1998 dollars) of about $7000 over the course of

one year.

Comment

Inpatient geriatric consultation may have an impact on care for the hospitalized older

patient, but the potential improvement in patient-safety outcomes is unclear. All-cause mortality

differences may be due to differences in patient selection, and the data for improvement in

functional outcomes suggests that certain patients may experience greater benefit than others.

Appropriate targeting of services to patients at high risk for adverse outcomes such as falls and

delirium seems to result in benefit. Consequently, multidisciplinary geriatric consultation and

other efforts directed towards preventing iatrogenic functional decline, the most common

complication of older hospitalized patients, deserve careful attention.

Identified problems in the reviewed studies include inadequate targeting of individuals

who would most benefit from the intervention, potential between-group cross-contamination,

and differences in local expertise in carrying out recommended interventions. Lack of

effectiveness in some studies may reflect poor compliance with team suggestions or inadequate

staffing to implement a consultant’s recommendations, regardless of desire to comply. Lack of

control over the direct management of the patient could also represent a serious shortcoming that

limits effectiveness of this practice.

Multidisciplinary geriatric consultative teams, in contrast to specialized geriatric

evaluation and management (GEM) units, provide expertise in geriatric care throughout a

hospital, but in a consultative role. In comparing this strategy with GEM units or Acute Care for

Elders (ACE) units, several differences should be noted. Multidisciplinary teams are less

expensive to organize and can be implemented within a shorter period of time. Since older

patients reside throughout an institution, there is also greater opportunity to reach a larger

number of patients when the consultation team is not single-unit based. There is no bed limit,

and the capacity of the team to provide interventions is therefore limited by their available time

rather than the number of beds in any one unit. The resources required to assemble an
317

experienced geriatric team in a hospital that has no pre-existing geriatric expertise remains an

important consideration. In addition, costs associated with enhancing and monitoring adherence

with recommendations should be included when designing an effective program. Physical

redesign of the unit environments to accommodate special needs (eg, special flooring, bed

layout, reorienting devices) is likewise not part of this practice. Specially trained geriatric nurses

are also not available equally throughout the hospital, in contrast to designated geriatric inpatient

units, which have nurses focused exclusively on care of the older patient.

Notwithstanding these considerations, the practice of multidisciplinary geriatric

consultation services has high face validity. More research is needed to evaluate which patients

might receive maximal benefit for the associated resource commitment. Other areas for further

research include examining the problems most appropriate for geriatric assessment and

consultation in the hospital, developing strategies to improve adherence to and execution of

recommendations, and identifying the components of a successful and cost-effective consultation

team.
318

Table 29.1. Studies of multidisciplinary geriatric consultation services

Study Setting and

Participants

Study

Design,

Outcomes

Results

Allen,

19986

Becker,

19877

Saltz, 19888

McVey,

19899

185 patients at a VA

hospital, 1983-1984

Level 1,

Level 1

No significant differences in hospitalacquired complications (overall 38%

for both groups)

No statistically significant improvement

in functional status (activities of daily

living)

No statistically significant differences in

rehospitalization or placement

Compliance with recommendations:

71.7% overall (from 47-95% for

selected interventions)

Fretwell,

199013

436 patients at a

university-affiliated

hospital, 1985-1987

Level 1,

Level 1

No significant difference in mortality at

discharge

No significant differences in length of

stay, physical or cognitive function, or

hospital charges

Gayton,

198219

222 patients at a

Canadian universityaffiliated hospital, 1982-

1984

Level 2,

Level 1

No significant mortality difference up to 6

months follow-up, but trend favoring

intervention group

No significant differences in functional

status, length of stay, or mental status

between study groups

Hogan, 

198716

113 patients at a

Canadian tertiary care

hospital, 1984

Level 1,

Level 1

Mortality at 4 months lower in the

intervention group (p<0.05), but not at

12 months

Fewer medications on discharge (p<0.05)

and improved mental status (p<0.01)

in the intervention group

Hogan, 

199018

132 patients at a

Canadian hospital, 1985

Level 1,

Level 1

Decreased 6-month mortality in the

intervention group (p<0.01)

No significant difference in outcomes at

discharge

Improved functional ability at one year

but not at 3 or 6 months in the

intervention group

Kennie,

198817

144 orthopedic patients

at a U.K. district

hospital, year not stated

Level 1,

Level 1

Intervention patients more functionally

independent (p=0.005) at discharge

and were discharged to home at higher

rates (p=0.03)
319

Marcantoni

o, 200115

126 orthopedic patients

at an academic medical

center, year not stated

Level 1,

Level 1

Occurrence of delirium: 32% vs. 50% in

control group (p=0.04)

Adherence to recommendations: 77%

Ray, 

199714

482 residents in 14

nursing homes, 1993-

1995

Level 1,

Level 1

Lower rate of recurrent falls: 19% vs.

54% in control group (p=0.03)

Trend toward lower mean rate of injurious

falls

Reuben,

199511

2353 patients at 4 HMOrun hospitals, 1991-1994Level 1,

Level 1

No statistically significant differences in

mortality at up to one-year follow-up

No significant change in functional status

at 3 or 12 months

Thomas,

199312

120 patients at a

community hospital, year

not stated

Level 1,

Level 1

Reduced 6-month mortality: 6% vs. 21%

controls (p=0.01)

Trend toward improved functional status

in the intervention group

Hospital readmission in 6-months

significantly lower in the intervention

group

Winograd,

199310

197 men at a VA

hospital, 1985-1989

Level 1,

Level 1

No significant mortality differences

between groups

No significant change in physical

function, length of stay, or placement

between groups

Compliance with all recommendations:

67%
320

References

1. A profile of older Americans: 2000. [Washington, DC]: Administration on Aging. U.S.

Department of Health and Human Services, 2000.

2. Kramarow E, Lentzner E, Rooks R, Weeks J, Saydah S. Health and aging chartbook.

Health, United States, 1999. Hyattsville, Maryland: National Center for Health Statistics,

1999.

3. Winograd CH. Targeting strategies: an overview of criteria and outcomes. J Am Geriatr

Soc. 1991;39S:25S-35S.

4. Palmer RM. Acute hospital care of the elderly: minimizing the risk of functional decline.

Cleve Clin J Med. 1995;62:117-128.

5. American Hospital Association. Health Statistics, 2001 edition. Chicago, Illinois: Health

Forum, 2001.

6. Allen CM, Becker PM, McVey LJ, Saltz C, Feussner JR, Cohen HJ. A randomized,

controlled clinical trial of a geriatric consultation team. Compliance with

recommendations. JAMA. 1986;255:2617-2621.

7. Becker PM, McVey LJ, Saltz CC, Feussner JR, Cohen HJ. Hospital-acquired complications

in a randomized controlled clinical trial of a geriatric consultation team. JAMA.

1987;257:2313-2317.

8. Saltz CC, McVey LJ, Becker PM, Feussner JR, Cohen HJ. Impact of a geriatric

consultation team on discharge placement and repeat hospitalization. Gerontologist.

1988;28:344-350.

9. McVey LJ, Becker PM, Saltz CC, Feussner JR, Cohen HJ. Effect of a geriatric consultation

team on functional status of elderly hospitalized patients. Ann Intern Med. 1989;110:79-84.

10. Winograd CH, Gerety MB, Lai NA. A negative trial of inpatient geriatric consultation.

Lessons learned and recommendations for future research. Arch Intern

Med.1993;153:2017-2023.

11. Reuben DB, Borok GM, Wolde-Tsadik G, et al. A randomized trial of comprehensive

geriatric assessment in the care of hospitalized patients. N Engl J Med. 1995;332:1345-

1350.

12. Thomas DR, Brahan R, Haywood BP. Inpatient community-based geriatric assessment

reduces subsequent mortality. J Am Geriatr Soc. 1993;41:101-104.

13. Fretwell MD, Raymond PM, McGarvey ST, et al. The Senior Care Study. A controlled trial

of a consultative/unit-based geriatric assessment program in acute care. J Am Geriatr Soc.

1990;38:1073-1081.

14. Ray WA, Taylor JA, Meador KG, et al. A randomized trial of a consultation service to

reduce falls in nursing homes. JAMA. 1997;278:557-562.

15. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip

fracture: a randomized trial. J Am Geriatr Soc. 2001;49:In press.

16. Hogan DB, Fox RA, Badley BW, Mann OE. Effect of a geriatric consultation service on

management of patients in an acute care hospital. CMAJ. 1987;136:713-717.

17. Kennie DC, Ried J, Richardson IR, Kiamari AA, Kelt C. Effectiveness of geriatric

rehabilitative care after fractures of the proximal femur in elderly women: a randomised

clinical trial. BMJ. 1988;297:1083-1086.

18. Hogan DB, Fox RA. A prospective controlled trial of a geriatric consultation team in an

acute-care hospital. Age Ageing.1990;19:107-113.
321

19. Gayton D, Wood-Dauphinee S, de Lorimer M, Tousignant P, Hanley J. Trial of a geriatric

consultation team in an acute care hospital. J Am Geriatr Soc. 1987;35:726-736.

20. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged.

The index of ADL: a standardized measure of biological and psychosocial function. JAMA.

1963;185:914-919.

21. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental

activities of daily living. Gerontologist. 1969;9:179-186.

22. Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J.

1965;14:61-65.

23. Inouye SK, Van Dycke CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying

confusion: the Confusion Assessment Method. Ann Intern Med. 1990;113:941-948.

24. Stuck AE, Siu AL, Wieland GD, Adams J, Rubenstein LZ. Comprehensive geriatric

assessment: a meta-analysis of controlled trials. Lancet. 1993;342:1032-1036.

25. Winograd CH, Gerety MB, Brown E, Kolodny V. Targeting the hospitalized elderly for

geriatric consultation. J Am Geriatr Soc. 1988;36:1113-1119.
322
323

Chapter 30. Geriatric Evaluation and Management Units for Hospitalized

Patients

Joseph V. Agostini, MD

Dorothy I. Baker, PhD, RNCS

Sidney T. Bogardus, Jr., MD

Yale University Schools of Medicine and Public Health

Background

Inpatient care of elders with multiple co-morbidities requires close attention to the special

needs and geriatric syndromes that arise in this vulnerable population.1,2 One strategy to address

the risks of hospitalization is to provide care by a multidisciplinary team in a dedicated geriatric

unit, principally Geriatric Evaluation and Management (GEM) Units. This model of care, in

many ways similar to coordinated stroke units,3

 may improve mortality and other clinically

relevant outcomes compared with outcomes achieved on a general medical ward. An alternative

strategy, reviewed elsewhere in this Report, is the comprehensive geriatric consultation service,

analogous to a typical medical consultation team (see Chapter 29).

In a GEM unit, a multidisciplinary team provides comprehensive geriatric assessment,

detailed treatment plans, and attention to the rehabilitative needs of older patients. A typical team

is composed of a geriatrician, clinical nurse specialist, social worker, and specialists from such

fields as occupational and physical therapy, nutrition, pharmacy, audiology, and psychology.

GEM units are typically separate hospital wards that have been redesigned to facilitate care of

the geriatric patient. Multidisciplinary team rounds and patient-centered team conferences are

hallmarks of care on these units, which, in contrast to geriatric consultation services, have direct

control over the implementation of team recommendations.

Practice Description

In all the studies reviewed in this chapter, the GEM unit team included a physician

experienced in geriatric medicine, skilled geriatric nurses and rehabilitation specialists. (The

latter may not have been on site but were accessible). The teams completed multidimensional

geriatric assessments, conducted interdisciplinary team rounds, and provided comprehensive

discharge planning. Units were physically separate wards that were designed to facilitate

geriatric care. Acute Care of Elders (ACE) Units4

 incorporate the GEM unit design with

additional enhancements and admit patients with acute illnesses. ACE units often provide

improved flooring and lighting, reorienting devices, and other environmental improvements such

as common rooms for patient use. For example, in the ACE unit studied by Landefeld and

colleagues5

 the GEM unit concept was enhanced by the use of more nurse-initiated protocols and

a greater number of environmental and design modifications.

Both styles of unit emphasize the early assessment of risk factors for iatrogenic

complications and the prevention of functional decline.4,6 Studies of both are included in this

chapter.
324

Prevalence and Severity of the Target Safety Problem

One-third of hospitalized patients are aged 65 years and older. In 1996, although

comprising only 13% of the US population they accounted for 38% of the approximately 31

million discharges from non-government, acute care hospitals.7

 Since all hospitalized older

patients are potentially at risk, the target population is quite large. Appropriate selection of

patients who are at risk for hospital-related complications and who are likely to receive benefit

from this practice, however, would decrease this number.8

The target safety problems are preventable deaths and hospital-related functional decline

in older persons. The number of deaths that could be prevented if the practice were to be widely

implemented is unknown. On the other hand, since hospital-related functional decline occurs in

25 to 60% of older hospitalized patients, there is substantial opportunity to improve clinical

outcomes.9

 Other clinical problems explicitly studied in controlled trials include cognitive status

and nursing home placement.

Opportunities for Impact

Data from the American Hospital Association (AHA)10 indicate that fewer than half of

hospitals providing care for the elderly have geriatric acute care units or offer comprehensive

geriatric assessment. (see footnote in Chapter 29). Researchers in the field believe the number is

increasing. The Department of Veterans Affairs reports that in 1997 there were 110 active GEM

units, although some concentrate solely on outpatient assessment.11 A recent national survey12

identified at least 15 active ACE units, with average daily censuses ranging from 5 to 25

patients. Depending on the screening and targeting criteria used to identify eligible patients, the

potential for impact could be quite large and raises the question of the physical and manpower

capacity of these units to meet the apparent demand.

Study Designs

A structured literature search identified a systematic review13 that included 6 studies (4

randomized controlled trials,14-17 one retrospective cohort study with historical controls,18 and

one published abstract of a randomized controlled trial19). We also identified 2 randomized

controlled trials of ACE units5,20 that were published later (see Table 30.1). All of the cited

studies were single center in design. Five of the studies5,14,16,17,20 provided sufficient data to

evaluate the baseline level of function of enrolled patients.

Study Outcomes

All-cause mortality was reported in each study. For this outcome, most patients were

followed 6 or more months after hospitalization. Other clinically important outcomes measured

in some studies were functional status,5,14,16,17,20 cognitive status,14,16,17 length of stay,5,14-16,18,20

and discharge rates to institutional settings.5,14-20

Evidence for Effectiveness of the Practice

In some studies mortality during hospitalization, at 3 months, or at 6 months was reduced

in the intervention group but the differences failed to achieve statistical significance. A metaanalysis13 of 6 studies14-19 found the summary odds ratio for 6-month mortality was 0.65 (95%

CI: 0.46-0.91), using both published and unpublished data from the included trials. Tests for

heterogeneity across studies were reported with p<0.10 for the pooled analyses.
325

Cognitive function, as measured by the Kahn-Goldfarb Mental Status Questionnaire,21

showed no statistical improvement over the course of one study,17 nor did 2 other studies14,16

demonstrate improvement, using the Mini-Mental State Examination22 to assess mental status.

Two trials of ACE units examined functional status, using the basic activities of daily living

(ADL).23 Landefeld et al5

 reported statistically significant improvements, while Counsell et al20

found benefit in a composite outcome of ADL improvement and nursing home placement, but

not in discharge ADL levels alone. Two other studies also demonstrated statistically improved

functional status in the six months after randomization14 and at 12 months follow-up.17

In individual studies, GEM units were associated with a higher likelihood of home

residence, rather than in an institutional setting (skilled nursing facility or nursing home).5,14, 17

The meta-analysis by Stuck et al calculated a combined odds ratio that revealed a statistically

significant increase in patients discharged from GEM units who were living at home at 6 months

(summary odds ratio 1.80, 95% CI: 1.28-2.53) and 12 months (summary odds ratio 1.68, 95%

CI: 1.17-2.41) thereafter.13 ACE unit trials in a community hospital20 and a university hospital5

were also both successful in decreasing patient placement in institutional settings and would

likely have strengthened the summary estimate if included. Extrapolating their study findings to

the US population, Rubenstein and colleagues17 estimated that approximately 200,000 nursing

home admissions per year could be avoided using their geriatric evaluation unit approach.

Winograd noted that this multidisciplinary practice would potentially be more effective if target

populations were better identified and enrolled using specific criteria.8

Potential for Harm

No data suggest that GEM units were associated with harm.

Costs and Implementation

Implementation of the practice requires construction or redesign of hospital ward(s) to

create a suitable environment, training or recruiting experienced staff, establishing selection

criteria to determine patient eligibility, and implementing a continuous evaluation process to

assess clinical and non-clinical outcomes.

A working group has recommended including costs as an important outcome measure in

future studies of GEM units.24 Applegate and colleagues reported in a later analysis25 of their

randomized controlled trial14 that the increased costs associated with their intervention study

were not balanced by savings in subsequent health care spending, but if charges were adjusted

for days spent at home (versus in long-term care) the charges were similar. Lower direct costs

were demonstrated by one intervention study,17 particularly after adjusting for differences in

survival (mean institutional-care costs per year survived, $22,597 for intervention patients vs.

$27,826 for control-group patients). The study by Landefeld et al5

 reported mean hospital

charges of $10,289 for intervention patients compared with $12,412 for control patients, with

similar median charges (p=0.3). Additional costs of about $75,000 attributable to staffing and

physical redesign of the unit resulted in a cost of about $230 per patient in the intervention

group. Counsell et al,20 in a recent large randomized trial of an ACE intervention, reported no

difference in hospital costs for patients in the intervention group compared with the usual care

group ($5640 vs. $5754, respectively; p=0.68). Included in the costs was $28 per hospital day

per intervention patient, representing costs of the geriatric nurse specialist, unit medical director,

and unit renovations ($300,000).
326

Comment

Reasonable evidence supports the use of GEM units, despite varying findings across

individual studies with respect to their effectiveness at preventing outcomes such as mortality.

Nonetheless, mortality appears to be improved after pooling results of smaller trials. There is

good evidence that this model of care decreases nursing home placements, which in itself is a

noteworthy finding. Furthermore, the intervention costs may not be significantly higher in these

specialized units. The generalizability of the practice requires further examination, and the need

for multicenter studies, as advocated by a previous consensus group,26 has thus far not been

undertaken.

Limitations of this practice compared with multidisciplinary geriatric consultation teams

(Chapter 29) include limited bed availability in most units, decreased transferability of geriatric

practices throughout a hospital, and a larger resource commitment compared with a hospitalwide consultation team. The advantages of the GEM and ACE unit model are direct control over

implementation of clinical recommendations, the presence of dedicated geriatric nursing and

rehabilitative staff associated with the unit, and the beneficial effects of a ward designed to

address older patients’ needs. In sum, the practice of a dedicated GEM or ACE unit carries much

promise.
327

Table 30.1. Randomized Controlled Trials of Geriatric Evaluation and Management Units*

Study Study Setting Study

Design

All-Cause Mortality and Other Outcomes†

Stuck,

199313

6 studies (published 1983-

1991) in the US, UK,

Australia, and Canada,

involving 1090 patients

(meta-analysis of Refs. 14-

19)

Level 1A 6-month mortality: summary odds ratio 0.65

(95% CI: 0.46-0.91);

12-month mortality: summary odds ratio

0.77 (95% CI: 0.56-1.06)

Applegat

e, 199014

155 patients in a

university-affiliated

community hospital, 1985-

1987

Level 1 6-month mortality: 10% vs. 21% (p=NS);

After 6 months: greatest difference p=0.08

by log-rank test;

Improvement in ADLs: 3 of 8 ADLs better

in intervention group (p<0.05)

Counsell,

200020

1531 patients in a

community hospital, 1994-

1997

Level 1 Inpatient mortality: 3% vs. 4% (p=0.30);

Length of stay: no significant difference;

Long-term placement or decline in ADLs

At discharge: 34% vs. 40% (p=0.027);

At 12 months: percentages not reported

(p=0.022)

Gilchrist,

199815

222 women on an

orthopedic-geriatric service

in the UK, 1984-1986

Level 1 Inpatient mortality: 4% vs. 10% (p=0.06);

6-month mortality: 14% vs. 18% (p>0.1)

Harris,

199116

267 patients in an

Australian hospital, 1985-

1986

Level 1 Inpatient mortality: estimated from Figure 1

in paper, 8% vs. 6% (p=NS);

12-month mortality: 23% vs. 29% (p=NS)

Landefel

d, 19955

651 patients in a

university-affiliated

hospital, 1990-1992

Level 1 Inpatient mortality: 7% in both groups

(p=NS);

3-month mortality: 14% vs. 13% (p=NS);

Improvement in ADLs at discharge: 34%

vs. 24% (p=0.009);

Discharged to nursing home: 14% vs. 22%

(p=0.01)

Powell,

199019

203 patients in two

Canadian teaching

hospitals, year not stated

Level 1 Mortality: lower in intervention group;

timing not stated (p not stated);

Transferred to long-term care: fewer in

intervention group (p not stated)
328

Rubenstei

n, 198417

123 patients in a VA

hospital, 1980-1982

Level 1 Inpatient mortality: 14.3% vs. 15.0%

(p=NS);

12-month mortality: 23.8% vs. 48.3%

(p<0.005)

12-month improvement in basic functional

status: 48.4% vs. 25.4% (p<0.01)

12-month improvement in mental status:

35.6% vs. 22.4% (p=NS)

Teasdale,

198318

124 patients in a VA

hospital, 1981-1982

Level 3 Inpatient mortality: 12% vs. 14% (p=NS);

6-month mortality: 28% vs. 35% (p=NS)

* ADL indicates activities of daily living; NS, not statistically significant.

† Comparisons are reported as intervention group vs. control group.
329

References

1. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118:219-223.

2. Hirsch CH, Sommers L, Olsen A, Mullen L, Winograd CH. The natural history of

functional morbidity in hospitalized older patients. J Am Geriatr Soc. 1990;38:1296-1303.

3. Stroke Unit Trialists Collaboration. How do stroke units improve patient outcomes? A

collaborative systematic review of the randomized trials. Stroke. 1997;28:2139-2144.

4. Palmer RM, Counsell S, Landefeld CS. Clinical intervention trials: the ACE unit. Clin

Geriatr Med. 1998;14:831-849.

5. Landefeld CS, Palmer RM, Kresevic DM, Fortinsky RH, Kowal J. A randomized trial of

care in a hospital medical unit especially designed to improve the functional outcomes of

acutely ill older patients. N Engl J Med.1995;332:1338-1344.

6. Palmer RM, Landefeld CS, Kresevic D, Kowal J. A medical unit for the acute care of the

elderly. J Am Geriatr Soc. 1994;42:545-552.

7. Kramarow E, Lentzner E, Rooks R, Weeks J, Saydah S. Health and aging chartbook.

Health, United States, 1999. Hyattsville, Maryland: National Center for Health Statistics,

1999.

8. Winograd CH. Targeting strategies: an overview of criteria and outcomes. J Am Geriatr

Soc. 1991;39S:25S-35S.

9. Palmer RM. Acute hospital care of the elderly: minimizing the risk of functional decline.

Cleve Clin J Med.1995;62:117-128.

10. American Hospital Association. Health Statistics, 2001 edition. Chicago, Illinois: Health

Forum, 2001.

11. Veterans Administration. VA programs for senior veterans. Geriatric evaluation and

management program. Available at: http://www.va.gov/seniors/health/gem.htm. Accessed

May 14, 2001.

12. Raziano DB, Jayadevappa R, Valenzula D, Weiner M, Lavizzo-Mourey RJ. Do Acute Care

for the Elderly (ACE) units work? Paper presented at: American Geriatrics Society Annual

Meeting; May 10, 2001; Chicago, IL. 2001.

13. Stuck AE, Siu AL, Wieland GD, Adams J, Rubenstein LZ. Comprehensive geriatric

assessment: a meta-analysis of controlled trials. Lancet. 1993;342:1032-1036.

14. Applegate WB, Miller ST, Graney MJ, Elam JT, Burns R, Akins DE. A randomized,

controlled trial of a geriatric assessment unit in a community rehabilitation hospital. N Engl

J Med. 1990;322:1572-1578.

15. Gilchrist WJ, Newman RJ, Hamblen DL, Williams BO. Prospective randomised study of

an orthopaedic geriatric inpatient service. BMJ. 1988;297:1116-1118.

16. Harris RD, Henschke PJ, Popplewell PY, et al. A randomised study of outcomes in a

defined group of acutely ill elderly patients managed in a geriatric assessment unit or a

general medical unit. Aust N Z J Med. 1991;21:230-234.

17. Rubenstein LZ, Josephson KR, Wieland GD, English PA, Sayre JA, Kane RL.

Effectiveness of a geriatric evaluation unit. A randomized clinical trial. N Engl J Med.

1984;311:1664-1670.

18. Teasdale TA, Shuman L, Snow E, Luchi RJ. A comparison of placement outcomes of

geriatric cohorts receiving care in a geriatric assessment unit and on general medicine

floors. J Am Geriatr Soc. 1983;31:529-534.

19. Powell C, Montgomery P. The age study: the admission of geriatric patients through

emergency [abstract]. Age & Ageing. 1990;19(Suppl. 2):P21-P22.
330

20. Counsell SR, Holder CM, Liebenauer MA, et al. Effects of a multicomponent intervention

on functional outcomes and process of care in hospitalized older patients: a randomized

controlled trial of Acute Care for Elders (ACE) in a community hospital. J Am Geriatr Soc.

2000;48:1572-1581.

21. Kahn RL, Goldfarb AI, Pollack M, Peck A. Brief objective measures for the determination

of mental states in the aged. Am J Psychiatry. 1960;117:326-328.

22. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading

the cognitive state of patients by the clinician. J Psychiatr Res. 1975;12:189-198.

23. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged.

The index of ADL: a standardized measure of biological and psychosocial function. JAMA.

1963;185:914-919.

24. Hedrick SC, Barrand N, Deyo R, et al. Working group recommendations: measuring

outcomes of care in geriatric evaluation and management units. J Am Geriatr Soc.

1991;39S:48S-52S.

25. Applegate WB, Graney MJ, Miller ST, Elam JT. Impact of a geriatric assessment unit on

subsequent health care charges. Am J Public Health. 1991;81:1302-1306.

26. Kramer A, Deyo R, Applegate W, Meehan S. Research strategies for geriatric evaluation

and management: conference summary and recommendations. J Am Geriatr Soc.

1991;39S:53S-57S.
331

Section E. General Clinical Topics

Chapter 31. Prevention of Venous Thromboembolism

Chapter 32. Prevention of Contrast-Induced Nephropathy

Chapter 33. Nutritional Support

Chapter 34. Prevention of Clinically Significant Gastrointestinal Bleeding in Intensive Care

Unit Patients

Chapter 35. Reducing Errors in the Interpretation of Plain Radiographs and Computed

Tomography Scans

Chapter 36. Pneumococcal Vaccination Prior to Hospital Discharge

Chapter 37. Pain Management

Subchapter 37.1. Use of Analgesics in the Acute Abdomen

Subchapter 37.2. Acute Pain Services

Subchapter 37.3. Prophylactic Antiemetics During Patient-controlled Analgesia

Therapy

Subchapter 37.4. Non-pharmacologic Interventions for Postoperative Plan
332
333

Chapter 31. Prevention of Venous Thromboembolism

Jennifer Kleinbart, MD

Mark V. Williams, MD

Kimberly Rask, MD, PhD

Emory University Schools of Medicine and Public Health

Background

Venous thromboembolism (VTE) refers to occlusion within the venous system. It

includes deep vein thrombosis (DVT), typically of the lower extremities, and embolism to the

pulmonary vasculature. Distal DVT is occlusion confined to the deep calf veins, while

thrombosis at or above the popliteal vein is considered proximal DVT. A distal DVT becomes

clinically important if it extends proximally, where the chance of pulmonary embolization (PE)

is clinically significant.

In hospitalized patients, VTE occurs with relatively high frequency. A patient’s risk of

VTE varies depending on multiple factors including age, medical condition, type of surgery,

duration of immobilization, and the presence of an underlying hypercoagulable state such as

malignancy. Measures to prevent VTE have been widely studied for many reasons, including

VTE’s high incidence, its associated mortality and morbidity, its cost of treatment, and its

treatment-related complications.

VTE is often clinically silent. As a result, studies evaluating the efficacy of preventive

measures generally screen patients who are asymptomatic. As widespread screening is not

recommended in general practice, the incidence of VTE in most studies appears higher than that

encountered in clinical practice. The importance of clinically undetected VTE is not fully

understood.

Practice Description

Both mechanical and pharmacologic interventions have been evaluated for prevention of

VTE (Table 31.1). Mechanical devices include graduated elastic stockings (ES) and intermittent

pneumatic compression (IPC); pharmacologic measures include low dose unfractionated heparin

(LDUH), low molecular weight heparin (LMWH), warfarin, and aspirin .

Prevalence and Severity of the Target Safety Problems

There are over 23 million surgeries performed each year in the United States.1

 The

frequency of DVT and PE varies by type of procedure and specific patient risk factors, as set

forth below. In general, without prophylaxis DVT occurs after approximately 20% of all major

surgical procedures and PE in 1-2%. Over 50% of major orthopedic procedures are complicated

by DVT and up to 30% by PE if prophylactic treatment is not instituted.2

In addition, of the more than 31 million patients admitted each year for medical

conditions, up to 16% of patients will develop DVT in the absence of prophylaxis.1,2
334

Opportunities for Impact

Despite the frequency with which VTE occurs in hospitalized patients, and the wellestablished efficacy and safety of preventative measures, prophylaxis is often underused or used

inappropriately. One survey of general surgeons found that 14% did not use VTE prophylaxis.3

Another survey of orthopedic surgeons found that only 55% placed all hip fracture patients on

VTE prophylaxis, and 12% never used prophylaxis.4

 When performing total hip replacement

(THR) and total knee replacement (TKR), 81-84% of surgeons placed all patients on

prophylaxis, and 3-5% used no prophylaxis. Taken together, these data imply that VTE

prophylaxis is used in 92% of THR patients, 89% of TKR patients, and 73% of hip fracture

repairs. For spinal procedures, 21-38% of surgeons used prophylaxis with all patients, while 46-

64% did not use prophylaxis with any patients, an overall rate of prophylaxis of 25-44%.4

 A

more recent chart review of Medicare patients over age 65 undergoing major abdominothoracic

surgery from 20 Oklahoma hospitals found that only 38% of patients were given VTE

prophylaxis.5

 Of patients considered at very high risk for VTE, the same percentage received

some form of prophylaxis, but only 66% of those received appropriate preventive measures.5

Another chart review of high-risk patients at 10 acute care US hospitals found that some

type of VTE prophylaxis was used in 94% of orthopedic patients and 75% of abdominal surgery

patients.6

 However, the 1995 American College of Chest Physician grade A recommendations7

(those therapies supported by the most rigorously designed studies) were followed in only 84%

of THRs, 76% of TKRs, 45% of hip fracture repairs, and 50% of abdominal surgery patients.

Compliance with grade A recommendations was no better in the 3 hospitals that had critical

pathways, pocket guides, or a policy for VTE prophylaxis.6

Inadequate VTE prophylaxis among medical patients may be even more prevalent. In one

study, only 33% of patients admitted to a medical intensive care unit received VTE prophylaxis.

Eighty-seven percent of these patients had one risk factor, and over 50% had multiple risks for

VTE.8

 Another study found that of patients who developed VTE during admission or within 30

days of discharge, 48% had not received prophylaxis during hospitalization. Most of these were

medical patients.9

Study Designs and Outcomes

There are a large number of randomized control trials (RCTs) and high quality metaanalyses that examine the efficacy of VTE prophylaxis. Most studies considered surgical rather

than medical patients. Several differences in study design may account for heterogeneity among

these studies, including differences in patients or procedures, the intervention (type, duration, or

dose of prophylaxis), the method used to diagnosis VTE, the outcome measured (distal or

proximal DVT, fatal or nonfatal PE), and whether the endpoint was a clinical event or one found

by routine screening.

The “gold standard” for diagnosis of DVT is contrast venography, which is generally

used in studies screening high-risk patients. Venography may detect a significant number of clots

that are not clinically important, and is often technically limited.10 Other common screening

methods are fibrinogen leg scanning (fibrinogen uptake test, FUT) and duplex ultrasonography,

both of which have low sensitivity for calf vein thrombosis.11,12 Meta-analysis of studies using

the FUT in orthopedic patients showed a sensitivity of 55% for calf vein thrombosis and 45% for

all DVT, with a specificity of 92%.11 For detection of calf vein thrombosis, duplex

ultrasonography had a sensitivity and specificity of 39% and 98% in symptomatic hospitalized

patients, and of 13% and 92% in patients undergoing arthroplasty.12 In studies of general surgery
335

patients, the incidence of DVT was 25% when diagnosis was made by FUT, and 19% when

confirmed by venogram.2

 However, in trials of VTE prophylaxis using elastic stockings in

neurosurgical patients, the study using FUT found a DVT rate of 9%, while 3 others using

venography found the rate of DVT to be 28%.2

In many studies, all patients are screened for DVT, although several studies only tested

for DVT if clinical signs or symptoms occurred. Clearly, in the latter a number of DVT are

missed; however, the clinical importance of these asymptomatic clots is unknown.

The gold standard for diagnosis of pulmonary embolus is pulmonary angiography.

However, reliable evidence confirms that combining clinical probability with results of

ventilation-perfusion scanning is an accurate and less invasive method of making this

diagnosis.13 Most studies report the incidence of symptomatic or fatal PE. Studies rarely screen

for PE in asymptomatic patients. Silent pulmonary embolism may occur in up to 50% of patients

with proximal DVT, however, the clinical importance of these emboli is unclear.14

Evidence for Effectiveness of the Practice

Studies of VTE prophylaxis are best grouped by the population at risk (Table 31.2). The

sections that follow describe the prevalence of thromboembolism in patients in each category

and discuss the efficacy of various prophylactic strategies.

General Surgery

For general surgery patients not receiving VTE prophylaxis, the incidence of DVT

confirmed by venogram is 19%. Proximal DVT occurs in 7% of patients, PE in 1.6%, and fatal

PE in 0.9%.2

In general surgery patients, the risk of VTE is highest in those undergoing major surgery

who are over the age of 40 and have an underlying hypercoagulable state, prior VTE, or cancer.

(Patients with spinal cord injury, trauma, and those undergoing hip or knee arthroplasty or hip

fracture surgery also fall in this risk group and are discussed separately below). Incidence rates

for patients in this “very high” risk group are as follows: calf DVT, up to 80%; proximal DVT,

20%; PE, 10%; and up to 5% may suffer a fatal PE if no prophylaxis is provided.2

 The risk of

VTE is lowest in those surgical patients who are young, otherwise healthy, and whose surgeries

are “minor.” Such patients have incident rates as follows: calf DVT, 2%; proximal DVT, 0.4%,

PE , 0.2%; and fatal PE , 0.002%.

Numerous studies show that both LDUH and LMWH reduce the risk of proximal DVT,

PE, and fatal PE in patients undergoing general surgery. Pooled results from 46 randomized

trials show that prophylaxis of general surgical patients with LDUH compared with placebo

reduced the risk of DVT (diagnosed by FUT or FUT confirmed with venography) by 68%, (from

25% [95% CI: 24-27%] to 8% [95% CI: 7-8%]).2

 LMWH has comparable efficacy to LDUH for

prevention of VTE, and may be more effective for preventing proximal DVT and PE.2,15,16

Pooled results (though heterogeneity was present) from 26 studies showed that high dose

LMWH (>3400 anti-Xa units) does not reduce DVT more than low dose LMWH does (<3400

anti-Xa units), but it does increase wound hematomas.16 Both IPC and ES significantly reduce

overall incidence of DVT, but have not been shown to diminish the incidence of proximal DVT

or PE in general surgical patients.17-20
336

Orthopedic Patients

All studies included in the evaluation of prophylaxis for orthopedic patients used

venography to diagnose DVT.

Total Hip Replacement

Within 7-14 days after total hip replacement (THR), patients not receiving prophylaxis

have an incidence of total and proximal DVT of 54% and 25%, respectively. Asymptomatic PE

may occur in 5-15%, symptomatic PE in 1-2%, and fatal PE in 0.1-0.4%.2,21 In patients

undergoing THR, many RCTs have shown that both mechanical and pharmacologic measures

are highly effective in the prevention of VTE.

A meta-analysis of 52 RCTs showed that patients receiving prophylaxis with LMWH,

LDUH, warfarin, aspirin or IPC had fewer total DVTs (proximal plus distal).21 IPC and ES

reduce distal DVT but do not significantly reduce proximal DVT in these patients.2,17 Compared

with placebo, prophylaxis with warfarin or LMWH resulted in the greatest reduction in proximal

DVT: a reduction of 70-80% with either method (risk of proximal DVT with warfarin 5-6%, RR

6.3% [95% CI: 4.7-8.4%]; with LMWH 6–8%, RR 7.7% [95% CI: 5.7-10.3%]).2,21 Both LMWH

and warfarin resulted in significantly fewer proximal DVTs compared with LDUH or IPC

(p<0.006 for each comparison).21 Pooled data from 5 trials that directly compared LMWH with

warfarin showed rates of proximal DVT of 3.4% and 4.8%, respectively.2

Following THR, symptomatic PE occurs significantly less frequently with warfarin

(0.16%, 95% CI: 0.002-0.59) and LMWH (0.36%, 95% CI: 0.22-0.57) than with placebo

(1.51%, 95% CI: 0.81-2.57). IPC, LDUH and aspirin do not reduce the risk of symptomatic PE

more than placebo. Fatal PE did not occur in any control patients in these trials, and occurred in

only 0.04-0.16% of those receiving prophylaxis with LMWH or warfarin.21

Recombinant hirudin, not approved in the United States for VTE prophylaxis, was found

more effective than LDUH or LMWH in reducing VTE in 3 trials of patients undergoing THR.

Bleeding did not increase.2

Hip Fracture Repair

Surgery for hip fracture carries a risk of DVT comparable to THR, however, the

incidence of PE is higher, with fatal PE occurring in 4-12% of patients.2

 As with hip replacement

surgery, LMWH and warfarin are the most effective agents for VTE prophylaxis for patients

undergoing hip fracture repair.2

 In a trial of over 13,000 hip fracture patients, aspirin

significantly reduced the risk of VTE, but with an absolute reduction of only 0.5% and a greater

increase in adverse events, particularly major bleeds.22 LDUH has been less well studied.

Total Knee Replacement

Compared to THR, knee replacement surgery carries a higher overall risk of DVT, but

lower risk of proximal DVT, with a prevalence of approximately 64% and 15%, respectively.

Total DVT and PE occur with the following frequencies in patients receiving prophylaxis:

aspirin, 53% and 12%; warfarin, 45% and 8%; and IPC, 17% and 6%. DVT occurs in 29% of

those treated with LMWH.23 While IPC reduces total DVT compared to aspirin and warfarin, it

does not significantly reduce proximal DVT.2,23

LMWH is the most effective method to prevent proximal DVT in patients undergoing

TKR. Data from 13 trials with 1740 patients show a 63% decreased risk of proximal DVT with

LMWH compared with placebo, 6% (95% CI: 5%-7%) vs. 15% (95% CI: 10%-23%).2

 Pooled
337

data show that aspirin (6 studies, 443 patients), warfarin (9 studies, 1294 patients), and LDUH (2

studies, 172 patients) do not significantly reduce proximal DVT following TKR.2

 Patients given

warfarin prophylaxis who were routinely screened with venography had an 8–12% risk of

proximal DVT. However, one study that followed patients for 3 months following TKR found

that patients who received warfarin had a rate of symptomatic VTE of only 0.8%.24

The incidence of PE is low in TKR patients. Studies in which PE was diagnosed by lung

scan or angiography showed the rate of symptomatic and asymptomatic PE in patients treated

with aspirin to be 1.3% and 11.7%, respectively, with warfarin 0.4% and 8.2%, and with IPC

0.5% and 6.3%. Symptomatic PE occurred in none of 177 patients receiving LMWH. No studies

of LMWH used routine lung scanning.23

Initiation of Therapy

Meta-analysis of patients undergoing THR found that LMWH initiated preoperatively

resulted in a lower risk of VTE than LMWH started postoperatively (10% vs. 15%, p=0.02).25

Major bleeding occurred less frequently in the group receiving preoperative LMWH (0.9% vs.

3.5%, p=0.01).

Duration of Therapy

The appropriate duration of VTE prophylaxis following orthopedic surgery is not clearly

established. However, it is clear that the increased risk of DVT persists post-discharge. In the

largest randomized trial of post-discharge LMWH, 533 patients received either 35 days of

dalteparin or 6 days of warfarin followed by placebo. Patients treated with extended LMWH had

significantly fewer total and proximal DVTs from day 6 to day 35 (for all DVT, dalteparin 4.8%

vs. placebo 10.5%, p=0.03; for proximal DVT, dalteparin 1% vs. placebo 4.8%, p=0.02), as well

as from day 1 to day 35 (dalteparin 2.6% vs. warfarin/placebo 9.2%, p=0.002). Seventy five

percent of these DVTs were asymptomatic. Symptomatic thrombi occurred in approximately 1-

2%. No patient had symptomatic, objectively documented pulmonary embolism.26 Pooled data

from this study and 5 others that compared in-hospital LMWH followed by LMWH or placebo

found that prolonged LMWH resulted in a 66% reduction in total DVT (14% vs. 27%) and a

66% reduction in proximal DVT (4% vs. 12%) by 35 days.2

Neurosurgery

Patients undergoing neurosurgical procedures carry a risk of developing DVT of

approximately 22%, and a risk of proximal DVT of 5%.2

 The risk of DVT is increased in

patients undergoing intracranial surgery compared to spinal surgery. Among patients undergoing

intracranial surgery, those with malignant tumors have a higher risk of DVT than those with

benign tumors. Increasing age and increasing duration of neurosurgery further increase the risk

of VTE. Meta-analysis of randomized studies comparing LMWH to placebo (one study) or

LMWH plus ES to ES alone (2 studies) in neurosurgical patients found that LMWH was

associated with a 38% reduction in total DVT (18% vs. 28%, p<0.001). Results in the two

studies evaluating proximal DVT found a 50% reduction with LMWH compared with placebo

(6% vs. 12%, p=0.008). There was no increase in major bleeding. All studies used venography to

assess DVT.27 The one randomized trial using LDUH (5000 U every 8 hours) found an 82%

reduction in all DVT (6% vs. 34%, p=0.005). In this trial, DVT was diagnosed with FUT.28 Two

meta-analyses evaluating IPC for VTE prophylaxis showed a 66% reduction in all DVT

compared with untreated controls (7% vs. 18-22%, p<0.001).2,17 Compared with placebo, IPC

also significantly reduced proximal DVTs in neurosurgical patients (6% vs. 17%, p<0.001).17
338

Trauma

Trauma patients, especially those with orthopedic injuries, are at very high risk for VTE.

DVT occurs in over 50% of these patients, proximal DVT in approximately 20%, and fatal PE in

up to 2%.2

 Few randomized trials have studied VTE prophylaxis in trauma patients. Metaanalysis shows that VTE prophylaxis, either with LDUH (4 randomized trials, OR 0.97, 95% CI:

0.35-2.6 for LDUH vs. control) or ES (3 randomized trials, OR 0.77, 95% CI: 0.27-2.2), did not

reduce DVT in trauma patients compared with placebo.29 Heterogeneity was present for all

comparisons due to differences in methods used to diagnose DVT and differences in trauma

populations. Pooled data from 4 studies (2 randomized and 2 nonrandomized) of LDUH versus

mechanical prophylaxis found no difference in risk of DVT (OR 1.16, 95% CI: 0.5-2.7).29 One

randomized trial comparing LDUH with LMWH in trauma patients screened with venography

found that DVT was reduced by 30% with enoxaparin (31% vs. 44%, p=0.01).30 Of the 265

patients randomized, only one patient (in the LMWH group) suffered a PE.

Acute Spinal Cord Injury

The risk of DVT (diagnosed by FUT or impedance plethysmography) in patients with

acute spinal cord injury ranges from 40-90%.2

 The only trial using screening venography in

patients with acute spinal cord injury who were not receiving prophylaxis found DVT in 81%

and proximal DVT in 35%.31

Prophylaxis in acute spinal cord injury has not been well studied. In the only study

evaluating use of IPC, proximal DVT occurred in 40% of patients with IPC alone, and in 25% of

patients with IPC combined with aspirin and dipyridamole.32 One randomized trial with 35

patients found that LMWH (tinzaparin 3500U daily) compared to LDUH (5000U three times a

day) reduced DVT from 16% to 0%, a reduction that did not reach statistical significance.33

However, a later prospective cohort study diagnosed DVT in 13% of 48 patients prophylactically

treated with LMWH.34 In both studies, screening for DVT was done with ultrasound or

ultrasound plus impedance plethysmography, with confirmation by venography. Of 15 acute

spinal cord injury patients from a randomized trial of major trauma patients, DVT was detected

in 67% of those given LDUH and 50% with LMWH. Proximal DVT occurred in 13% receiving

LDUH and none prophylaxed with LMWH.30
339

Medical Patients

VTE prevention in hospitalized medical patients has not been studied as extensively as in

surgical patients. DVT occurs in 24% of patients with myocardial infarction, and is reduced by

71% with LDUH compared with placebo with no increase in bleeding (4 studies with 165

patients).2

 However, most patients with acute myocardial infarction receive full anticoagulation

for treatment of the acute coronary syndrome.

After ischemic stroke, 55% of untreated patients develop DVT. Prophylaxis with either

LDUH or LMWH given for 10-14 days reduces DVT by 56%, from 55% (95% CI: 49%-60%) to

24% (95% CI: 20%-29%). Two studies directly comparing LDUH (5000 U three times daily) to

LMWH (enoxaparin 40 mg once daily), using venography for diagnosis, found greater reduction

in DVT with LMWH.2

Among hospitalized patients with other medical conditions, the rate of DVT is

approximately 16%.2

 A meta-analysis of studies of hospitalized patients with conditions other

than myocardial infarction or ischemic stroke given VTE prophylaxis with unfractionated or low

molecular weight heparin showed a 56% reduction in DVT (RR 0.44, 95% CI: 0.29-0.64) and a

52% reduction in PE (RR 0.48, 95% CI: 0.34-0.68). No significant difference was found between

LMWH and LDUH in incidence of DVT, PE, or mortality; however, major hemorrhage was

lower with LMWH than with LDUH (RR 0.48, 95% CI: 0.23-1.00).35

Another randomized trial comparing enoxaparin with placebo in 866 medical patients

found a 63% reduction in overall VTE risk with enoxaparin (40 mg) compared with placebo in

the first 14 days (5.5% vs. 15%, RR 0.37, 95% CI 0.22-0.63). Proximal DVT was reduced by

65% (1.7% vs. 4.9%, RR 0.40, 95% CI 0.23-0.69). Significant reductions in total and proximal

DVT persisted at 110 days. VTE was not reduced in the group receiving 20 mg of enoxaparin.

The most common medical conditions were acute infectious disease, acute respiratory failure,

New York Heart Association Class III or IV congestive heart failure.36

The risk of VTE is higher in patients with malignant disease, especially those with

adenocarcinoma or brain tumors. Factors associated with increased VTE in cancer patients

include chemotherapy, surgery, and indwelling central venous catheters. Breast cancer patients

treated with tamoxifen also have higher rates of VTE. In patients with indwelling central venous

catheters who received low dose warfarin (1 mg per day), upper extremity DVT was reduced by

75% (9.5% vs. 37.5%).37

In summary, for general surgery patients who are at moderate risk or greater for VTE,

LDUH and LMWH are the most effective methods for prophylaxis. IPC also provides effective

DVT prevention, but in very high risk patients should only be used in conjunction with heparin.

For orthopedic procedures, LMWH and warfarin are the most effective preventive measures.

Neurosurgical patients should receive LMWH or LDUH, while in acute spinal cord injury or

trauma, LMWH provides the largest reduction in VTE. For stroke or medical patients, LMWH

and LDUH show the greatest benefit for VTE prevention (see Table 31.2).

Summary of Prophylaxis Recommendations

For general surgery patients at moderate to high risk, LDUH and LMWH have

comparable effectiveness for prevention of VTE, with similar bleeding risks. LDUH is generally

more cost-effective. For high risk patients, IPC has not been consistently shown to prevent

proximal DVT (See Table 31.3).

For major orthopedic procedures (THR, TKR, hip fracture repair), prophylaxis with

LMWH or warfarin results in the greatest benefit, with a small increase in bleeds compared with
340

no prophylaxis, but no difference between the two agents. Warfarin may be more cost-effective,

but necessitates monitoring and dose adjustment. This should be considered in choosing between

the two agents.

IPC, LMWH, and LDUH are all acceptable methods of prophylaxis for neurosurgical

patients. Each effectively reduces proximal DVT with no increase in major bleeding. There are

no data on cost-effectiveness of prophylaxis for these patients.

Data for prophylaxis of trauma patients does not show conclusive VTE reduction with

any agent. However, the risk of VTE among these patients is high and prophylaxis should be

considered, especially for those with orthopedic injuries. LMWH is a safe method of prophylaxis

and has not been shown to increase major bleeds in blunt trauma patients. However if a patient is

at high risk for major bleeding, IPC should be considered.

For medical patients, LDUH and LMWH are both effective for reducing VTE. LDUH

may result in slightly more bleeding, but is more cost-effective. Patients at high risk for bleeding

should be given prophylaxis with ES or IPC.

Potential for Harm

There is no documented risk associated with mechanical devices, although there is a

potential risk that patients’ legs will be examined less frequently. The major risk of

pharmacologic prophylaxis is bleeding. Bleeding is typically considered major when the

hemoglobin decreases by at least 2 g/dL, when red blood cell transfusion is necessary, when

intracranial or retroperitoneal bleeding occurs, or when bleeding requires surgical intervention.

Another consequence of heparin therapy may be thrombocytopenia.

For general surgery, there is no difference in the risk of major bleeding between LMWH

and LDUH, although fewer minor bleeds may occur with LMWH (RR 0.64, 95% CI 0.58-

0.70).15 However, when evaluated according to dose of LMWH, compared with LDUH, lowdose LMWH (<3400 anti-Xa units) resulted in a significant decrease in wound hematomas,

while high-dose LMWH carries a significant increase.16

Bleeding related to VTE prophylaxis is uncommon after orthopedic surgery. The greatest

risk of bleeding occurs with LDUH (3.4% vs. 0.56% with placebo, RR 3.46, p<0.0001).21 The

risk of bleeding with LMWH is significantly greater than with placebo, but the absolute risk

increase (ARI) is small (for TKR, 2.8% vs. 0.9%, ARI 1.7%; for THR, 1.2% vs. 0.9%, ARI

0.3%).21 With warfarin, bleeding occurs in 0.5% of patients following THR.2

 Studies comparing

LMWH to warfarin for THR found no difference in major bleeding.21,26

Among neurosurgical patients treated with LMWH, there was a two-fold increase in all

bleeding compared with controls (6% vs. 3%, p=0.02), however, there was no significant

difference in major bleeds.27 Similar results were found in a study using LDUH.28

Blunt trauma patients who received enoxaparin 30mg q12h started within 24 hours of

hospitalization had no bleeding events attributed to this treatment. This included patients with

closed head injury, grade III liver injury, and grade IV splenic injury.38

Prophylaxis of medical patients with enoxaparin 40 mg/d did not increase the risk of

bleeding compared to placebo. Of 711 patients treated with LMWH, there were no cases of

severe thrombocytopenia (platelet count less than 50,000 per cubic millimeter).36 Compared with

LDUH, prophylaxis with LMWH results in fewer major bleeds (RR 0.48, 95% CI: 0.23-1.00).35

Costs and Implementation

A Swedish study evaluating general surgery patients at moderate risk for VTE and hip

surgery patients found LDUH and LMWH were more cost-effective than no prophylaxis, and
341

LMWH was more cost-effective than LDUH.39 An economic evaluation using decision analysis

compared LDUH and LMWH for patients undergoing colorectal surgery. There was no

difference in risk of VTE between groups. Per 1000 patients treated, prophylaxis with

enoxaparin compared with LDUH resulted in 12 excess major bleeds and an additional cost of

$145,667.40 This supports LDUH as a more cost-effective measure for patients undergoing

general surgery.

Meta-analysis of studies of the cost-effectiveness of VTE prophylaxis for patients

undergoing hip arthroplasty found that with a 2.6 to 1 price ratio between LMWH and LDUH,

use of LMWH would save the health care system approximately $50,000 per 1000 patients

treated.41 For VTE prophylaxis after TKR, LMWH was more cost-effective than warfarin, saving

$2401 per 100 patients ($9197 vs. $11,598 per 100 patients).42 This study was done in Canada,

where LMWH is less costly than in the United States. Another meta-analysis of THR patients

found that LDUH would decrease the cost of care related to DVT by $200 per patient. Compared

with warfarin, LMWH would be more effective in preventing DVT (expected DVT rate

420/10,000 with warfarin and 250/10,000 with LMWH), and death from VTE (110/10,000 with

warfarin and 70/10,000 with LMWH). However, preventing one death with LMWH use instead

of warfarin would cost approximately $12,000.43

In medical patients, LDUH given 3 times daily was found to be more cost-effective than

LMWH, with a savings per 1000 patients of $10,753 compared with enoxaparin 40 mg/d, and

$15,000 compared with enoxaparin 20 mg/d.44 The higher cost associated with enoxaparin 20

mg/d results from the higher incidence of complications with this regimen. This supports use of

LDUH as the preferred method of prophylaxis for medical patients at the present time, though

this is an area of active investigation. No studies were found evaluating the cost of DVT

prophylaxis in neurosurgery patients.

Comment

As noted earlier, despite the clear evidence of effectiveness, DVT prophylaxis is

underused. The reasons for this underuse have not been completely elucidated, nor have the

optimal strategies for improving prophylaxis been fully identified. Various strategies have been

tried in an effort to improve physician utilization of appropriate VTE prophylaxis. One hospital

studied the impact of educational programs promoting guidelines for prophylaxis. It found that

presentations to staff, distributions of cards with the hospital’s guidelines, and posters increased

prophylaxis of surgical patients from 59% to 70%, and to 77% for high-risk patients (see also

Chapters 51 and 54).45

In another study, a computer-based clinical decision support system (CDSS) (see Chapter

53) providing information pertaining to VTE prophylaxis was used in an orthopedic surgery

department of a teaching hospital. The investigators monitored the impact of CDSS use in 1971

patients undergoing orthopedic surgery. Compliance with guidelines was 83% during control

periods and 95% during intervention periods. Inappropriate practice decisions occurred almost 4

times more frequently during control versus intervention periods.46

A third study evaluating methods to improve VTE prophylaxis among intensive care unit

patients found that staff education improved use of appropriate prophylaxis from 38% to 62%.

When required computerized order sets were added to education, appropriate prophylaxis

increased to 97%.47

These studies suggest that either a knowledge gap or lack of awareness may exist among

practitioners. For institutions or groups attempting to improve appropriate use of measures to

prevent VTE, guidelines made available via computerized support systems or order sets provide
342

the most effective means of implementing appropriate VTE prophylaxis, especially when these

systems are linked to effective educational programs.
343

Table 31.1. Mechanical and pharmacologic preventative measures for VTE

Practice Type Description Comment

Graduated Elastic

Stockings (ES)

Mechanical Fitted hose that extend

above the knee

Fitted hose are more

efficacious than non-fitted

Intermittent

pneumatic

compression (IPC)

Mechanical Devices fitted over lower

extremities that

sequentially inflate and

deflate

Aspirin Pharmacologic Usually 325 mg/d

Warfarin Pharmacologic 5-10 mg started the day

of or after surgery; adjust

to achieve an INR of 2-3

Monitoring of INR needed

Low-dose

unfractionated

heparin (LDUH)

Pharmacologic Generally 5000 U

subcutaneous bid or tid,

though some studies have

adjusted dose to maintain

PTT at high end of

normal

Contraindicated if active

bleeding or history of

thrombocytopenia; no 

need to follow coagulation

studies (unless adjusted

dose is used)

Low Molecular

Weight Heparin

(LMWH)

Pharmacologic Dose depends on type of

surgery and VTE risk*

No need to monitor

coagulation studies

* LMWH dosing: Enoxaparin 20 mg SC daily (moderate risk surgery) or 40 mg SC daily (can go

up to 30 mg SC q12h for high risk general surgery, major trauma or acute spinal cord injury);

dalteparin 2500–5000 U SC daily; nadroparin 2500 U SC daily; tinzaparin 3500-4500 U SC

daily (may be dosed 75U/kg/d for orthopedic surgery).
344

Table 31.2. Summary of DVT risk and prophylactic methods providing significant risk

reduction*

Surgery/

Condition

Risk of all DVT in

untreated patients

Type of

Prophylaxis

Risk Reduction with

Prophylaxis

Number of

Studies

ES 44% 3

LDUH 68% 47

LMWH 76% 21

General

Surgery2 25%

IPC 88% 2

LMWH 70% 30

THR2 54%

warfarin 59% 13

LMWH 52% 13

TKR2,23 64%

IPC 73% 6

Neuro- LMWH 38% 3

surgery27,28 28%

LDUH 72% 1†

Trauma2,30 30-60% LMWH 30%

(compared to LDUH) 1

Acute Spinal

Cord Injury2 80% Not established

LDUH 56% 5

LMWH 58% 3 Ischemic

stroke2 55%

Danaparoid 82% 4

76% 2†

LMWH

39% 2 Medical

conditions2 16%

LDUH 61% 3†

* DVT indicates deep venous thrombosis; ES, graduated elastic stockings; IPC, intermittent

pneumatic compression; LDUH, low-dose unfractionated heparin; LMWH, low molecular

weight heparin; THR, total hip replacement; and TKR, total knee replacement.

† DVT diagnosed by fibrinogen uptake test (FUT)
345

Table 31.3. Recommended VTE prophylaxis for surgical procedures and medical

conditions*

Surgery/Condition Recommended

Prophylaxis

Comments

General Surgery – low-risk: minor

procedures, <40 years old, no additional

risks

None Early ambulation

General Surgery – moderate risk: minor

procedure but with risk factor, nonmajor

surgery age 40-60 with no risks, or major

surgery <40 years with no risks

LDUH, LMWH, ES,

or IPC

General Surgery – high risk: nonmajor

surgery over age 60 or over age 40 with

risks.

LDUH, LMWH

General Surgery – very high risk: major

surgery over age 40 plus prior VTE, cancer

or hypercoagulable state

LDUH or LMWH

combined with ES

or IPC

May consider postdischarge

LMWH or perioperative warfarin

Elective Hip Replacement LMWH or warfarin May combine with ES or IPC; start

LMWH 12 hours before surgery,

12-24 hours after surgery, or 4-6

hours after surgery at half the dose

for initial dose. Start warfarin

preoperatively or immediately

after surgery, target INR 2.0-3.0.

Elective Knee Replacement LMWH or warfarin

Hip Fracture Surgery LMWH or warfarin

Neurosurgery IPC, LDUH or

LMWH

Start LMWH post-surgery

Trauma LMWH with ES or

IPC

If high risk of bleeding, may use

ES and/or IPC alone.

Acute Spinal Cord Injury LMWH Continue LMWH during

rehabilitation or convert to

warfarin (target INR 2.5)

Ischemic Stroke LDUH, LMWH, or

danaparoid

Medical Conditions LDUH or LWMH

If contraindication to

anticoagulant, use ES or IPC.

* Adapted with permission from Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA,

et al. Prevention of venous thromboembolism. Table: Regimens to prevent VTE, pp. 156S-158S. Chest

2001. Sixth ACCP Consensus Conference on Antithrombotic Therapy.2

 ES indicates graduated elastic

stockings; INR, international normalized ratio; IPC, intermittent pneumatic compression; LDUH, lowdose unfractionated heparin; LMWH, low molecular weight heparin; and VTE, venous

thromboembolism.
346

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for prevention of venous thromboembolism. JAMA. 2000;283:2816-2821.

47. Levi D, Kupfter Y, Seneviratne C, Tessler S. Computerized order entry sets and intensive

education improve the rate of prophylaxis for deep vein thrombophlebitis. Chest.

1998;114S:280S.
349

Chapter 32. Prevention of Contrast-Induced Nephropathy

Lorenzo Di Francesco, MD

Mark V. Williams, MD

Emory University School of Medicine

Background

Radiocontrast-induced nephropathy (RCIN) represents an increasingly common cause of

treatment-related renal failure1-3 and increases mortality independent of other risk factors.4

 Major

risk factors for RCIN include chronic renal insufficiency,2,3,5 diabetes mellitus2,3,5 (especially

when accompanied by renal insufficiency1

), any condition associated with decreased effective

circulating volume,6

 and use of large doses of contrast media.2,3,5,6

For at-risk patients, clinicians must use their judgment to determine if imaging modalities

that do not involve contrast media are an acceptable alternative to contrast studies. In many

cases, however, such alternatives do not exist. Moreover, RCIN occurs in patients without

obvious risk factors. Thus, strategies for reducing the incidence of RCIN include not just risk

factor identification, but modification of these risk factors, choice of contrast media less likely to

cause RCIN, and administration of therapeutic agents that further reduce the risk of RCIN.

Practice Description

The specific practices reviewed in this chapter are:

• Use of high versus low osmolar iodinated contrast media to prevent RCIN.7

• Use of a standard intravenous or oral hydration protocol for patients with risk

factors for RCIN.

8-10 Typical intravenous protocols evaluated consist of normal saline

administered at 75 mL/hr beginning at 12 hours before and ending 12 hours after the

procedure. Oral protocols require ingestion of 1000 mL of water during the 10 hours

prior to the procedure, followed by intravenous normal saline at 300 mL/h for 30-60

minutes and continued for a total of 6 hours after the procedure.

• Use of a standard hydration protocol supplemented by pretreatment with

theophylline11-15 (various doses and schedules)

• Use of a standard hydration protocol supplemented by pretreatment with Nacetylcysteine16 (600 mg bid one day before and day of procedure)

Single studies evaluating atrial natriuretic peptide, prostaglandin E117 and captopril18

were not reviewed, as the data are too preliminary, despite findings that suggest a reduction in

the risk of RCIN. Although the evidence supporting the use of N-acetylcysteine largely comes

from a single study as well, we do review this practice because the study was large, published in

a prominent journal, and has received considerable attention among clinicians.16

The use of calcium channel blockers in preventing RCIN was not evaluated, as the

existing literature predominantly indicates the practice is ineffective.19-23
350

Prevalence and Severity of the Target Safety Problem

While definitions of RCIN vary, most study definitions include a 25% increase in serum

creatinine (SCr) and/or at least a 0.5 mg/dL increase in SCr within 48 hours of contrast

administration. Using this definition, one large community-based study of 1826 patients

undergoing invasive cardiac procedures reported a rate of RCIN of 14.5%.2

 A controlled

prospective study of the onset of RCIN after contrast-enhanced brain CT found an incidence of

2.1% in low-risk patients without diabetes mellitus or chronic renal insufficiency versus 1.3% in

a similar control group that did not receive any contrast (p=NS).24 In comparison, patients in a

prospective controlled study undertaken to determine the risk of nephrotoxicity from contrast

radiography in patients with diabetes and renal insufficiency (SCr >1.7mg/dL) found a 9%

incidence of RCIN.1

The cumulative effect of multiple risk factors increasing the risk of RCIN was

demonstrated in one uncontrolled study that evaluated the effect of 5 factors (contrast volume

>200 mL, albumin <3.5 g/L, diabetes, serum sodium <135 mmol/l, SCr>1.5 mg/dL).3

 When all

risk factors were present the risk of RCIN was 100%, compared with just 1.2% when none were

present. While most patients with RCIN suffer little morbidity and recover to near baseline renal

function within 7-10 days (and thus we characterize it as a Level 2 outcome), rare patients

require temporary dialysis. Two studies suggested that the development of RCIN may lead to

longer lengths of stay8,11 and one large retrospective study showed that hospitalized patients who

develop RCIN had a mortality rate of 34% compared with 7% in control subjects, even after

controlling for underlying co-morbidities.4

 The development of RCIN appeared to increase the

risk of death from non-renal causes such as sepsis, bleeding, respiratory failure and delirium.

Opportunities for Impact

Few studies have rigorously evaluated current practice patterns among radiologists or

cardiologists with respect to evaluation of a patient’s threshold creatinine prior to ordering

contrast procedures. One survey study of academic and private practice radiology departments

found that only about 20% of practices routinely obtain serum creatinine levels before contrast

administration.25 Interestingly, when patients were known to have a high-risk condition like

diabetes, approximately 60% of the same practices would require a serum creatinine before

contrast administration. Therefore, many high-risk patients are not identified prior to undergoing

contrast radiography studies. In addition, no studies have evaluated the frequency with which

physicians recommend pre-hydration for patients prior to contrast studies. Overall, physicians

and institutions do not follow a consistent practice in screening patients for risk factors for RCIN

prior to the use of contrast radiography. If rigorous evidence identifies patients at risk for RCIN,

and effective, standardized preventative measures are developed and implemented, there is

substantial opportunity to reduce morbidity.

Study Designs

The literature on strategies for preventing RCIN includes: one meta-analysis evaluating

the nephrotoxicity of high versus low-osmolality iodinated contrast media,7

 one randomized

controlled study of pre-treatment with acetylcysteine16 for high-risk patients, one randomized

controlled trial of pre-treatment with prostaglandin E117 for high-risk patients, and 5 randomized

controlled trials assessing the impact of theophylline11-15 in preventing RCIN. Unfortunately,

each of the studies of theophylline employed different routes and dosages (and, in fact, one of
351

the studies used aminophylline, rather than theophylline). Table 32.1 summarizes the salient

features of these studies.

One randomized trial compared inpatient versus outpatient hydration regimens,26 but we

found no randomized controlled trial that evaluated pre-hydration versus no hydration. Thus,

support for the standard use of pre-hydration to prevent RCIN is extrapolated from randomized

controlled studies of saline versus saline plus additional pre-treatment agents like mannitol,

furosemide and dopamine8-10 and smaller observational studies6,27,28 evaluating the benefits of

pre-hydration.

Study Outcomes

Studies evaluated Level 2 outcomes, primarily by measuring changes in serum creatinine,

creatinine clearance or glomerular filtration, and assessing the frequency of developing acute

renal failure after radiocontrast infusions. Most studies defined RCIN as a 25% increase in

creatinine and/or at least a 0.5 mg/dL increase in serum creatinine within 48 hours of contrast

administration.

Evidence for Effectiveness of the Practice

All of these studies (Table 32.1) evaluated the effects of various prophylactic measures to

reduce the incidence of RCIN. Use of low-osmolar contrast media was supported by one large

meta-analysis 7 that compared low versus high osmolar contrast media. Low osmolar contrast

media was found to be less nephrotoxic than high osmolar contrast media, with an odds ratio for

RCIN of 0.61. Among patients with baseline renal insufficiency (SCr >1.4 mg/dL) the odds ratio

of developing RCIN was 0.5 if low osmolar instead of high osmolar contrast media was used.

As previously noted, no randomized controlled trials have evaluated the efficacy of prehydration versus no pre-hydration. Data from 3 randomized controlled trials8-10 using prehydration versus other pre-treatments and pre-hydration revealed that pre-hydration alone was

equivalent to pre-hydration and low dose dopamine or mannitol,8

 and, in one study, superior to

pre-hydration and furosemide.10 The incidence of RCIN in patients with SCr >1.6 mg/dL or

creatinine clearance <60 mg/min treated with pre-hydration alone undergoing cardiac

catheterization was 11%; excluding the patients with SCr >3 mg/dL, the incidence was only 4%.8

One retrospective, observational study of high-risk patients undergoing cardiac catheterization

supports the benefit of pre-hydration (>500 mL of 0.9% NS in the pre-catheterization period,

p• 0.01) in reducing RCIN.6

 In addition, 2 observational studies without controls27,28 showed

that pre-hydration in high-risk patients was associated with low rates of RCIN, although one of

these studies27 used a stricter definition for RCIN (increase in BUN by 50% or 20 mg/dL, and/or

increase in SCr of 1 mg/dL within 24 hours).

A recent study of the oral antioxidant acetylcysteine in combination with pre-hydration in

high-risk patients with renal insufficiency showed significant protective effect against RCIN

versus pre-hydration plus placebo.16 This protective effect appeared to be even more significant

among patients with more advanced renal dysfunction and SCr >2.5 mg/dL. The overall relative

risk reduction of 90% observed in this study is so large that it raises the possibility of some sort

of bias or other explanation for the observed results. Additional studies of this practice would be

valuable, despite the safety and low cost of N-acetylcysteine.

Studies employing theophylline are more controversial. Three randomized control trials

showed a significant protective effect of various dosages and administration routes of

theophylline among low-risk patients with relatively normal baseline renal function.12-14 All 3

studies showed theophylline to be protective against a decrease in glomerular filtration rate
352

(GFR) or creatinine clearance (CrCl) after contrast administration. On the other hand, 2 studies

conducted in high-risk patients with renal dysfunction showed no effect for theophylline in

reducing RCIN.11, 15 Thus, insufficient evidence supports the use of theophylline as prophylaxis

against RCIN in high-risk patients.

Potential for Harm

The impact of a system to identify high-risk patients prior to contrast radiography and

implement aggressive prophylactic measures to reduce the incidence of RCIN has not been

studied. While most patients will not experience any harm from contrast, the potential for

“harm” due to delayed or cancelled investigations may be greater than the harm prevented by

screening for risk factors, aggressive hydration, or use of particular pre-treatment regimens.

Costs and Implementation

At least 4 studies have evaluated the cost-effectiveness of low-osmolality versus highosmolality contrast media.29-32 In all 4 studies, the selective use of low-osmolar contrast media

was more cost-effective than its universal use because of the overall small benefits were

outweighed by the considerable increased institutional costs. Alternatively, a standardized

system to identify high-risk patients and implement the simple prophylactic treatment of prehydration would diminish the frequency of the target problem. It would require collaboration

between the patients’ own physician and the personnel performing the particular contrast study

(radiology department, radiologist, diagnostic/interventional cardiologist). This type of

intervention could be implemented as part of a hospital-based pathway (see Chapter 52) targeted

at reducing radiocontrast-induced nephropathy.

There are no cost-effectiveness or feasibility studies that evaluate protocols for

aggressive identification of high-risk patients undergoing contrast radiography and utilization of

standardized hydration protocols to reduce RCIN. Two studies suggest most patients with

normal renal function (SCr <1.7 mg/dL) can be easily identified by simple questionnaire,

resulting in significant cost savings from a reduction in the number of routine serum creatinine

levels obtained prior to imaging.33,34 The cost-effectiveness of using pharmacologic pretreatment with N-acetylcysteine or theophylline has not been studied.

Comment

In summary, patients with multiple risk factors for RCIN who need radiography with

contrast media should receive pre-hydration and low osmolar iodinated contrast. Overall, there

appears to be indirect evidence that RCIN can be attenuated by pre-hydrating high-risk patients.

Clearly, the use of low osmolar contrast media is associated with less RCIN, but its high cost

militates against routine use in all patients. We believe that it should continue to be reserved for

the patient with multiple risk factors for RCIN. While newer pre-treatment regimens like Nacetylcysteine, prostaglandin E1, and captopril look very promising in preventing RCIN, these

results need to be replicated in further studies. Finally, many institutions would benefit from a

hospital-based pathway that identifies patients with multiple risk factors for RCIN prior to

contrast radiography. Guidelines (Chapter 51) for appropriate pre-hydration and the timely use

of low osmolar contrast media to reduce the development of RCIN would be beneficial.
353

Table 32.1. Studies of strategies for preventing radiocontrast-induced nephropathy

(RCIN)*

Study Setting Study Design,

Outcomes

Results

Low osmolar contrast media

Meta-analysis of the relative

nephrotoxicity of high (HOCM)

vs. low (LOCM) osmolar

iodinated contrast media7

Level 1A,

Level 2

LOCM less nephrotoxic than HOCM; pooled

p=0.02

Odds of ARF with LOCM 0.61 times that of

HOCM (95% CI: 0.48-0.77). Patients with RF at

baseline, odds of ARF were 0.5 (CI: 0.36-0.68).

Pre-hydration plus diuresis

Patients with SCr >1.8mg/dL

randomized to IVF, IVF +

furosemide, IVF + furosemide +

low dose IV dopamine +/-

mannitol (if post-cardiac

catheterization, PCWP <20

mmHg)9

Level 1,

Level 2

No differences in rates of renal failure between

groups. Rates of RCIN 21.6% if UOP >150

mL/h, 45.9% if UOP <150 mL/h.

Patients with SCr >1.6mg/dL or

CrCl <60mL/min randomized to

IVF, IVF + mannitol or

furosemide pre-cardiac

catheterization8

Level 1,

Level 2

No statistically significant difference in RCIN,

among the three groups. After exclusion of

patients with SCr >3 mg/dL, RCIN in patients

with IVF alone 4%, IVF + mannitol 24%

(p=0.02), IVF + furosemide 25% (p=0.02). LOS

increased by 4 days in RCIN group.

Patients with SCr >1.7 or CrCl

<60mL/min randomized to IVF +

furosemide vs. discretion of

treating physician during contrast

radiography10

Level 1,

Level 2

SCr increased by 0.42 mg/dL +/- 0.20 treatment

group vs. 0.023 mg/dL +/- 0.073 (p<0.01)

controls. Significant weight loss in treatment

group vs. controls (p<0.03)

Observational study of “high risk”

patients with SCr >1.9 mg/dL

who underwent cardiac cath6

Level 3,

Level 2

Statistically significant risk factors for RCIN:

volume of contrast used (168+/- 11 vs. 122+/16

mL, p=0.001) and use of prehydration (>500mL

0.9% normal saline in preceding 24 hrs, p<0.01)
354

Table 32.1. Studies of strategies for preventing radiocontrast-induced nephropathy

(cont.)*

Study Setting Study Design,

Outcomes

Results

N-Acetylcysteine

Patients with SCr >1.2 mg/dL or

CrCl <50 mL/min randomized to

pre-hydration (IVF) with oral

acetylcysteine or placebo prior to

contrast CT16

Level 1,

Level 2

RCIN developed in 2% treatment group vs. 21%

control group (p=0.01). Among patients with

SCr >2.5 mg/dL, RCIN 0% treatment vs. 42%

controls (p=0.02)

Theophylline

Patients randomized to

theophylline (165mg IV x 1) vs.

placebo prior to contrast

radiography.12

Level 1,

Level 2

GFR reduced 85.4 +/- 3.8 mL/min controls vs.

107 +/-3.6 mL/min treatment group (p• 0.001).

Patients randomized to

theophylline (2.8 mg/kg orally

q12 x 2 days) vs. placebo prior to

contrast radiography with LOCM

or HOCM.13

Level 1,

Level 2

CrCl after LOCM decreased by ~18% at 24 hrs

in control (p<0.05) vs. no significant change over

48 hrs in treatment group. CrCl after HOCM

decreased by ~40% at 24 hrs and remained low

at 48 hrs in controls (p<0.01) vs. ~24% at 24/48

hrs in the treatment groups (p<0.05). CrCl after

HOCM significantly lower in control vs.

treatment group (p<0.01).

Patients randomized to prehydration + theophylline (5mg/kd

IV) or placebo prior to contrast

CT or DSA.14

Level 1,

Level 2

GFR decreased at 4 hrs and 2 days in placebo (88

+/- 40 to 75 +/- 20 mL/min, 89+/- 41 mL/min to

66+/- 32 mL/min, p<0.01) with no significant

change in CrCl in the treatment group.

Patients with SCr >1.5mg/dL

randomized to pre-hydration vs.

pre-hydration with low dose

dopamine or aminophylline prior

to cardiac catheterization.11

Level 1,

Level 2

Overall incidence of RCIN was 38%. No

significant differences were noted among the

groups. LOS was longer in patients with RCIN

(7.1 days vs. 3.1 days, p=0.02).

Patients randomized to prehydration + theophylline (270 mg

q am/540 mg q pm 2d before, 3d

after) or placebo prior to contrast

CT or DSA.15

Level 1,

Level 2

No significant differences in SCr or CrCl

between groups (RCIN 3.4% controls, 5.7% in

treatment, p=NS).

* ARF indicates acute renal failure; CI, confidence interval; CrCl, creatinine clearance; CT, computed

tomography scan; DSA, digital subtraction angiography; GFR, glomerular filtration rate; IVF,

intravenous fluids; LOS, length of stay; NS, not statistically significant; PCWP, pulmonary capillary

wedge pressure; SCr, serum creatinine; and UOP, urine output.
355

References

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material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or

both. A prospective controlled study. N Engl J Med. 1989;320:143-149.

2. McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after

coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med.

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3. Rich MW, Crecelius CA. Incidence, risk factors, and clinical course of acute renal

insufficiency after cardiac catheterization in patients 70 years of age or older. A

prospective study. Arch Intern Med. 1990;150:1237-1242.

4. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort

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5. Lautin EM, Freeman NJ, Schoenfeld AH, Bakal CW, Haramati N, Friedman AC, et al.

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risk patients undergoing cardiac catheterization. J Am Soc Neprhol. 1990;1:330A.

7. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and lowosmolality iodinated contrast media. Radiology. 1993;188:171-178.

8. Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol, and

furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N

Engl J Med. 1994;331:1416-1420.

9. Stevens MA, McCullough PA, Tobin KJ, Speck JP, Westveer DC, Guido-Allen DA, et al.

A prospective randomized trial of prevention measures in patients at high risk for contrast

nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced

Nephropathy Clinical Evaluation. J Am Coll Cardiol. 1999;33:403-411.

10. Weinstein JM, Heyman S, Brezis M. Potential deleterious effect of furosemide in

radiocontrast nephropathy. Nephron. 1992;62:413-415.

11. Abizaid AS, Clark CE, Mintz GS, Dosa S, Popma JJ, Pichard AD, et al. Effects of

dopamine and aminophylline on contrast-induced acute renal failure after coronary

angioplasty in patients with preexisting renal insufficiency. Am J Cardiol. 1999;83:260-

263, A5.

12. Kolonko A, Wiecek A, Kokot F. The nonselective adenosine antagonist theophylline does

prevent renal dysfunction induced by radiographic contrast agents. J Nephrol.

1998;11:151-156.

13. Katholi RE, Taylor GJ, McCann WP, Woods WT, Jr., Womack KA, McCoy CD, et al.

Nephrotoxicity from contrast media: attenuation with theophylline. Radiology.

1995;195:17-22.

14. Erley CM, Duda SH, Schlepckow S, Koehler J, Huppert PE, Strohmaier WL, et al.

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after

contrast media application. Kidney Int. 1994;45:1425-1431.

15. Erley CM, Duda SH, Rehfuss D, Scholtes B, Bock J, Muller C, et al. Prevention of

radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency

by hydration in combination with the adenosine antagonist theophylline. Nephrol Dial

Transplant. 1999;14:1146-1149.
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16. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of

radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl

J Med. 2000;343:180-184.

17. Koch JA, Plum J, Grabensee B, Modder U. Prostaglandin E1: a new agent for the

prevention of renal dysfunction in high risk patients caused by radiocontrast media? PGE1

Study Group. Nephrol Dial Transplant. 2000;15:43-49.

18. Gupta RK, Kapoor A, Tewari S, Sinha N, Sharma RK. Captopril for prevention of contrastinduced nephropathy in diabetic patients: a randomised study. Indian Heart J.

1999;51:521-526.

19. Seyss C, Foote EF. Calcium-channel blockers for prophylaxis of radiocontrast-associated

nephrotoxicity. Ann Pharmacother. 1995;29:187-188.

20. Khoury Z, Schlicht JR, Como J, Karschner JK, Shapiro AP, Mook WJ, et al. The effect of

prophylactic nifedipine on renal function in patients administered contrast media.

Pharmacotherapy. 1995;15:59-65.

21. Russo D, Testa A, Della Volpe L, Sansone G. Randomised prospective study on renal

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22. Neumayer HH, Junge W, Kufner A, Wenning A. Prevention of radiocontrast-mediainduced nephrotoxicity by the calcium channel blocker nitrendipine: a prospective

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23. Cacoub P, Deray G, Baumelou A, Jacobs C. No evidence for protective effects of

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function following infusion of radiologic contrast material. A prospective controlled study.

Arch Intern Med. 1985;145:87-89.

25. Lee JK, Warshauer DM, Bush WH, Jr., McClennan BL, Choyke PL. Determination of

serum creatinine level before intravenous administration of iodinated contrast medium. A

survey. Invest Radiol. 1995;30:700-705.

26. Taylor AJ, Hotchkiss D, Morse RW, McCabe J. PREPARED: Preparation for Angiography

in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for

cardiac catheterization in mild-to-moderate renal dysfunction. Chest. 1998;114:1570-1574.

27. Eisenberg RL, Bank WO, Hedgcock MW. Renal failure after major angiography. Am J

Med. 1980;68:43-46.

28. Teruel JL, Marcen R, Herrero JA, Felipe C, Ortuno J. An easy and effective procedure to

prevent radiocontrast agent nephrotoxicity in high-risk patients. Nephron. 1989;51:282.

29. Barrett BJ, Parfrey PS, Foley RN, Detsky AS. An economic analysis of strategies for the

use of contrast media for diagnostic cardiac catheterization. Med Decis Making.

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30. Michalson A, Franken EA, Smith W. Cost-effectiveness and safety of selective use of lowosmolality contrast media. Acad Radiol. 1994;1:59-62.

31. Caro JJ, Trindade E, McGregor M. The cost-effectiveness of replacing high-osmolality

with low-osmolality contrast media. AJR Am J Roentgenol. 1992;159:869-874.

32. Steinberg EP, Moore RD, Powe NR, Gopalan R, Davidoff AJ, Litt M, et al. Safety and cost

effectiveness of high-osmolality as compared with low-osmolality contrast material in

patients undergoing cardiac angiography. N Engl J Med. 1992;326:425-430.
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358
359

Chapter 33. Nutritional Support

Neil Winawer, MD

Mark V. Williams, MD

Emory University School of Medicine

Background

There is a consensus that nutritional support should be routinely provided to intensive

care unit (ICU) patients.1

 Hospitalized patients with malnutrition (macronutrient and/or

micronutrient deficiency) suffer from increased infectious morbidity, prolonged hospital stays,

and increased mortality.2

 Moreover, even those hospitalized medical and surgical patients

without antecedent malnutrition are typically subjected to stress, infection and impaired organ

function, resulting in a hypercatabolic state. Often these patients are unable to meet their caloric

needs, as they are either too sick or physically unable to ingest food. Although strong evidence

demonstrates that providing nutritional support for such patients results in improved clinical

outcomes, the optimal method of delivery, timing of administration, and specific formulation

requires further research.

Practice Description

There are several ways to provide nutritional support to patients in the ICU. Enteral

nutrition (EN) can be administered via transoral, transnasal, or percutaneous transgastric routes,

or by surgical jejunostomy. Total parental nutrition (TPN) is generally used when the enteral

route is either inaccessible or its use is contraindicated. It is also used as a supplement to enteral

feeding if adequate nutrition is not possible via the enteral route alone.

The total caloric requirement of critically ill patients can be estimated or directly

measured. Calorimetry, although accurate, is not practical in the clinical setting as it is costly,

time consuming, and requires technical skill. It is also unclear that exactly matching energy input

with energy expenditures improves patient outcomes. Therefore, a pragmatic approach is to

attempt administration of 25 kilocalories per kilogram ideal body weight per day for most

patients.3

 The total caloric daily requirement should be administered in a fluid volume consistent

with the patient’s needs (usually 1mL/kcal). Protein sources should comprise 15-20% of the total

daily calorie requirement. The generally accepted amount of protein is between 1.2 and 1.5 g/kg

per day, except in severe losses such as burns. Glucose should comprise 30-70% of the total

calories and fats 15-30%.1

Prevalence and Severity of the Target Safety Problem

Malnutrition in hospitalized patients often goes unrecognized.4,5 Early studies reported a

prevalence of malnutrition in 30-50% of hospitalized patients.6

 A later study revealed that up to

40% of patients were malnourished at the time of their admission.7

 The majority of these patients

continued to be nutritionally depleted throughout their hospital course. These patients are also at

a greater risk for the development of severe malnutrition than those patients whose nutritional

status was adequate at the time of admission.

Unfortunately, there is no single, readily available measure of malnutrition that is both

sensitive and specific in critically ill patients.1

 Most studies have used body mass index

(BMI=weight (kg)/height (m)) and/or anthropometry (measuring skin fold thickness) to assess

patients’ nutritional status.7

 BMI alone is not a sensitive indicator of protein-energy malnutrition

as it does not distinguish between depletion of fat or muscle.4

 In a large number of studies,
360

malnutrition has been defined as a BMI ≤20 kg/m and a triceps skin fold thickness (TSF) or midarm muscle circumference (MAMC) <15th percentile.7

 Patients with a BMI of ≤18 and ≤16 kg/m

with anthropometric measurements below the 5th percentile were considered to have moderate

and severe malnutrition respectively.7

 Weight loss exceeding 10% of ideal body weight (IBW)

also suggests malnutrition.1

Opportunities for Impact

Providing nutritional support has the potential to significantly reduce several clinically

relevant endpoints (eg, infectious complications, hospital stay, mortality). However, even when

malnutrition is recognized, adequate nutrition is often not delivered. Prescription of optimal

enteral nutrition to meet energy requirements ranged from 76% to 100% in a prospective survey

of 5 ICUs in the United Kingdom.8

 Another study of enteral nutrition among patients receiving

no oral nutrition in medical and coronary care units at 2 US university-based hospitals,

documented that physicians ordered only 65.6% of daily goal requirements and only 78.1% of

this was actually delivered.9

 A recent prospective study of both enteral and parenteral nutrition in

a French university-affiliated ICU found that physicians prescribed only 78% of the mean caloric

amount needed by patients, and only 71% of this was effectively delivered.10 Efforts targeted at

increasing physician awareness of the problem and early delivery of appropriate nutrition may

improve patient outcomes.

Study Design

The field of nutritional support can be divided into several basic areas of investigation.

First, research has evaluated whether nutritional support is of benefit to malnourished critically

ill patients. Second, studies have compared the impact of EN versus TPN on patient outcomes.

Further investigations have looked at the timing of administering nutritional support. Lastly,

recent research has focused on the type of EN, specifically considering whether immuneenhancing formulas (immunonutrition) improve outcomes.

At least 26 randomized controlled trials (RCTs) have compared the use of TPN to

standard care (usual oral diet plus intravenous dextrose), and one meta-analysis reviewed these

studies.11 A different meta-analysis specifically reviewed the use of TPN in surgical patients.12 A

systematic review with meta-analysis (duplicated in the other publications11,12) included

evaluation of 6 randomized trials in surgical patients that compared the benefits of early enteral

nutrition with standard care.2

 Numerous randomized controlled trials have compared EN to TPN.

Three RCTs of surgical patients evaluated the merits of early enteral feeding postoperatively. A

few studies have compared EN delivered into the stomach versus into the small bowel (jejunum).

Several randomized controlled trials have studied the effects of using immunonutrition and we

found 2 meta-analyses of immune-enhancing enteral supplementation in critically ill patients

after trauma, sepsis or major surgery.

Study Outcomes

The majority of studies reported Level 1 outcomes including infectious complications

and mortality. Some measured hospital length of stay (Level 3) as well. Several studies

evaluating immunonutrition reported its effects on surrogate outcomes such as wound healing.

Studies evaluating immediate enteral nutrition in burn patients have also used surrogate markers.

Animal studies have assessed the effects of immunonutrition on gastrointestinal physiology as

well as wound strength.
361

Evidence for Effectiveness of the Practice

Nutritional supplementation in hospitalized patients may reduce mortality and is

associated with weight gain (see Table 33.1).13 However, there are no randomized controlled

trials comparing supplemental nutrition to starvation in critically ill patients. Research does show

that patients not receiving any nutritional support for more than 2 weeks postoperatively have a

much higher complication and mortality rate than patients receiving TPN or some short-term

glucose administration.14 A large body of research in the past 2 decades has focused on

determining the ideal type and method of delivery of nutritional support.

A meta-analysis comparing supplemental TPN to standard care (oral diet as tolerated and

intravenous dextrose) found no effect on mortality (relative risk (RR) 1.03, 95% CI: 0.81-1.31).11

There was a trend toward a lower complication rate among those receiving TPN (RR 0.84, 95%

CI: 0.64-1.09), but this is due mainly to benefit among malnourished patients.11 There are no

data from randomized controlled trials to support the use of supplemental TPN among patients

with an intact gastrointestinal tract (“If the gut works, use it”).

Several studies have evaluated the use of supplemental EN in surgical patients. These

studies often used surrogate outcomes, but one randomized double-blind trial of early EN versus

standard diet as tolerated following surgery found fewer total complications (26.7% vs. 63.3%,

p=0.009), fewer infectious complications (6.7% vs. 46.7%, p<0.001) and a trend towards a

reduction in hospital length of stay (8 vs. 11.5 days, p=0.08) with early EN.15 Based on this

evidence, early EN is recommended in critically ill surgical patients. There is no specific

research evaluating the benefits of supplemental EN in critically ill medical patients, but results

from research in surgical patients appear to be applicable.2

 In animal studies, EN promotes gut

motility, reduces bacterial translocation, prevents mucosal atrophy and stimulates the secretion

of IgA that helps to reduce infectious complications.3

 There is also evidence that EN improves

nutritional outcomes and results in greater wound healing.2

 A review of 5 trials studying

postoperative EN found no significant reduction in morbidity or mortality.6

 However, a recent

study of patients with non-traumatic intestinal perforation and peritonitis found there to be a total

of 8 septic complications in the early EN group versus 22 in the control group (p<0.05).16

Multiple studies comparing use of EN to TPN in critically ill medical and surgical

patients demonstrate that EN is safe, less expensive, and results in similar or better outcomes.2

Among patients with acute severe pancreatitis, those fed enterally had fewer total complications

(44% vs. 75%, p<0.05) and fewer septic complications (25% vs. 50%, p<0.01).17 In numerous

studies of surgical patients, EN also appears to be more effective than TPN. A study of patients

undergoing total laryngectomy revealed no difference in mortality or infectious complications.

However, the patients who received TPN had a longer length of stay (34 days vs. 11 days,

p<0.05).18 In another study of patients with abdominal trauma, those fed enterally had

significantly fewer septic complications (15.7% vs. 40%, p<0.02).19 A meta-analysis combining

data from 8 prospective randomized trials found that 18% of patients receiving EN developed

infectious complications compared with 35% in the TPN group (p=0.01).20 Of note, EN may not

be preferred to TPN in head-injured patients.2

 In a study of patients with head trauma there

appeared to be no significant difference in relation to infectious outcomes and mortality between

EN and TPN. However, patients fed enterally had a trend toward a higher incidence of aspiration

pneumonia (32% vs. 13%, p=0.11), though no difference in overall infections and mortality.21

The effects of preoperative TPN have been evaluated in 13 prospective randomized

controlled trials of patients undergoing surgical resection of a gastrointestinal tumor. Combining

the data from these studies reveals a modest reduction in surgical complications (approximately
362

10%) in those patients receiving TPN.6

 This benefit appears to be due entirely to significant

reduction in surgical morbidity among patients who are severely malnourished.22 Therefore,

preoperative TPN may be of benefit in severely malnourished patients undergoing major

gastrointestinal surgery, but EN should be used instead, if possible. The use of postoperative

TPN has been evaluated in 8 prospective randomized trials of patients undergoing

gastrointestinal surgery. Patients in the combined TPN group experienced an increased rate of

complications (27.3% vs. 16.0%; p<0.05). Thus, routine use of postoperative TPN in this setting

is not recommended.6

Since enteral administration is the preferred method of nutritional support, additional

research has focused on the utility of early administration of EN to severely ill surgical patients.

In animal studies early EN is associated with greater wound strength after abdominal surgery.23

In burn patients immediate EN was associated with a decrease in catecholamines and glucagons,

and improved nitrogen balance compared to delayed EN.24 A prospective randomized controlled

study evaluated the effect of immediate jejunal feeds in patients with major abdominal trauma.

The overall complication rate was similar in both groups, but 9 patients in the control group

developed postoperative infections versus 3 in the EN group (p<0.025).25 Although other studies

do not show a change in outcomes, based upon this data it is reasonable to begin EN as soon as

possible in surgical patients. More research is needed to evaluate the necessity of administering

EN into the jejunum.2

Recently, intense study has focused on use of immunomodulating enteral formulations

(containing arginine, glutamine, omega-3 fatty acids, and nucleotides). In animal and human

studies, specific immunonutrients have had favorable effects such as promotion of T-cell

blastogenesis, enhancement of cellular immunity and increased concentration of trienoic

eicosanoids.2

 The largest (n=390) prospective, double-blinded RCT comparing enteral

immunonutrition (IMPACTTM, Novartis Nutrition, Bern, Switzerland) to isocaloric,

isonitrogenous control enteral feed revealed no significant difference in hospital mortality rate in

the intention-to-treat analysis (48% vs. 44%, p=0.36).26 This study, conducted in a 13-bed adult

general ICU in a London teaching hospital, resulted in randomization of patients with higher

Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (p=0.07, ie, they were

“sicker”) to the immunonutrition group, with this possibly accounting for the slightly higher

mortality rate. Subgroup analyses of patients who received some enteral nutrition (n=369) and

therapeutic levels of enteral feeding (>2.5 L within 72 hours of ICU admission, n=101) also

showed non-significant higher mortality rates in the group receiving IMPACT. However, the

subgroup analyses also showed significant reductions in days of mechanical ventilation, length

of ICU stay, and overall hospital length of stay (LOS) in the group receiving immunonutrition

compared to the control group (see Table 33.1). Of note, the reductions in length of stay may be

attributable to the higher mortality rates in the group receiving immunonutrition, as more

patients died sooner in the immunonutrition group than the control group (ie, LOS reduced by

early death).27

A meta-analysis of 12 randomized controlled trials (including the aforementioned study)

comparing use of one of two commercially available enteral feeding preparations (IMPACTTM or

Immun-AidTM, McGaw, Irvine, CA) to standard enteral nutrition did not find any effect on

mortality (RR 1.05, 95% CI: 0.78-1.41).28 However, patients receiving enteral immunonutrition

had significant reductions in infection rate (RR 0.67, 95% CI: 0.50-0.89), ventilator days

(reduced 2.6 days, 95% CI: 0.1-5.1) and hospital length of stay (reduced 2.9 days, 95% CI: 1.4-

4.4).28 The benefits were most pronounced in surgical patients. Another meta-analysis of 11

prospective RCTs (not including the aforementioned RCT) also found reductions in the odds of
363

developing major infectious complications (odss ratio 0.47, 95% CI: 0.32-0.70), and hospital

length of stay (reduced 2.5 days, 95% CI: 1.0-4.0).29 Though there was no “significant”

difference in mortality between patients receiving immune-enhanced versus standard nutritional

support, there was a trend toward increased mortality (odds ratio 1.77, 95% CI: 1.00-3.12).29

Potential for Harm

TPN has been associated with an increase in septic complications. Patients may also be

placed at increased risk from attempts to obtain central venous access. While EN decreases the

overall rate of infectious complications when compared to TPN, it may place patients, especially

those with head injuries, at greater risk of aspiration pneumonia. Use of a promotility agent, such

as metoclopramide, has reduced this risk in one study.30

Costs and Implementation

TPN is itself expensive. Moreover, hospital costs can climb dramatically if patients who

receive TPN suffer infectious complications that prolong their hospital stay. Obtaining central

venous access also increases the costs of administration. Nutritional support teams (NSTs) can

help ensure that patients are receiving adequate nutrition while at the same time reducing the rate

of line complications.28 However, the use of NSTs is expensive and has not been subject to a

cost analysis.28 The economics of early postoperative enteral nutrition was studied in a recent

nonrandomized, prospective, clinical trial of patients undergoing bowel resections. There was a

reduction in variable cost of $1531 per success in the treatment group (p=0.02) and $4450 total

cost savings per success in the treatment group (p=0.04).31 Immunonutrition is significantly more

expensive than standard enteral formulas but in 2 prospective randomized controlled trials of

patients undergoing upper gastrointestinal surgery it has been shown to be cost-effective. In one

study, the cost per patient for nutrition and complications in the control group was $1633

compared to $783 in the immunonutrition group.32 In another study the cost per patient for

nutrition and complications in the control group was $1107 compared with $755 in the treatment

group.33

Comment

The literature on appropriate nutritional support for critically ill patients is complex to

analyze. A wide variety of treatment modalities have been evaluated in a fairly heterogeneous

patient population, making interpretation of the various studies difficult.

Nonetheless, there are several general recommendations that can be made. First,

malnutrition leads to poor outcomes and should be avoided or treated if present. Patients who

have prolonged starvation for more than 2 weeks are at a significantly increased risk for

complications. EN in these patients decreases this risk, and should be administered to all

critically ill medical and surgical patients who can tolerate it. There are no data to support the

use of TPN in critically ill patients who have a functional gastrointestinal tract. However, TPN

may be of benefit preoperatively when given electively to severely malnourished patients

undergoing gastrointestinal resection. Postoperative administration of TPN worsens outcomes.

There is no evidence to suggest that postoperative enteral nutrition is superior to advancing a

patient’s oral diet, as tolerated, if they are capable of eating, but research into early

administration of EN via the jejunum is ongoing.

Use of immune-enhanced EN appears to significantly reduce infectious complications,

number of days of mechanical ventilation, and overall hospital length of stay, though it does not

appear to affect overall mortality (and may increase it). Of note, study groups with increased
364

mortality rates may also have a diminished incidence of infectious complications and decreased

length of stay artifactually due to patients dying early in the study. One expert interpreted the

published research as strongly suggesting that immune-enhancing formulas should be used in

critically ill patients, especially surgical patients, despite their high cost.34 Nonetheless, a large

multicenter RCT is needed to resolve with certainty whether or not use of these expensive

formulas is safe and improves outcomes in critically ill patients before formally recommending

their widespread use.29
365

Table 33.1. Studies evaluating nutritional support*

Study Study Design,

Outcomes

Results (95% Confidence Interval)

Routine protein energy

supplementation in

adults; systematic

review13

Level 1A, Level

1

Reduced mortality: OR 0.66 (0.48 to 0.91)

Increased body weight gain (%):

Oral Sip Feeds: 2.39 (1.80 to 2.96)

Oral natural feeds: 5.36 (1.73 to 8.99)

Nasogastric feeding: 4.04 (3.15 to 4.94)

Percutaneous or enteral feeding, enterostomy:

-1.38 (-2.35 to -0.41)

TPN in critically ill

patients; metaanalysis11

Level 1A, Level

1

No effect on mortality: RR 1.03 (0.81 to 1.31)

Complication rate: RR 0.84 (0.64 to 1.09)

Complication rate (malnourished subgroup):

RR 0.52 (0.30 to 0.91)

TPN in surgical

patients; metaanalysis12

Level 1A, Level

1

No effect on mortality: RR 0.97 (0.76 to 1.24)

No effect on mortality (malnourished subgroup):

RR 1.13 (0.75 to 1.71)

Major complication rate (malnourished subgroup):

RR 0.52 (0.30 to 0.91)

Immunonutrition in

critically ill patients;

systematic review and

meta-analysis28

Level 1A, Level

1

No effect on mortality: RR 1.05 (0.78 to 1.41)

Reduction in infection rate: RR 0.67 (0.50 to 0.89)

Reduction in days of mechanical ventilation:

2.6 days (0.1 to 5.1)

Reduction in hospital LOS: 2.9 days (1.4 to 4.4)

Immunonutrition in

patients with critical

illness and cancer;

meta-analysis29

Level 1A, Level

1

Trend toward increased mortality:

OR 1.77 (1.00 to 3.12)

Reduction in infectious complications:

OR 0.47 (0.32 to 0.70)

No reduction in pneumonia risk: OR 0.91 (0.53 to 1.56)

Reduction in hospital LOS: 2.5 days (4.0 to 1.0)

EN vs. TPN in

seriously ill

hospitalized patients;

systematic review and

meta-analysis2

Level 1A, Level

1

Reduction in septic complications:

EN 18% vs. TPN 35% (p=0.01)

Reduction in infectious complications:

EN 16% vs. TPN 35% (p=0.01)

Enteral

immunonutrition in the

critically ill; doubleblind randomized

controlled trial26

Level 1, Level

1

Overall analysis (immunonutrition vs. control formula)

Mortality: 48% vs. 44% (p=0.36)

Total days of mechanical ventilation (median):

4 vs. 4 days (p=NS)

Hospital LOS (median): 12 vs. 13 days (p=NS)

Early enteral feeding subgroup

Total days of mechanical ventilation (median):

6 vs. 10.5 days (p=0.007)

Hospital LOS (median): 15.5 vs. 20 days (p=0.03)

* LOS indicates length of stay; NS, not statistically significant; OR, odds ratio; and RR, relative risk.
366

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2. Heyland DK. Enteral and parenteral nutrition in the seriously ill, hospitalized patient: A

critical review of the evidence. Journ of Nutr Health & Aging. 2000;1:31-41.

3. Jolliet P, Pichard C, Biolo G, Chiolero R, Grimble G, Leverve X, et al. Enteral nutrition in

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4. McWhirter JP, Pennington CR. The incidence and recognition of malnutrition in hospital.

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5. Potter JM, Klipstein K, Reilly JJ, Roberts MA. The nutritional status and clinical course of

acute admissions to a geriatric unit. Age Ageing. 1995;24:131-136.

6. Torosian MH. Perioperative nutrition support for patients undergoing gastrointestinal

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7. Beattie AH, Prach AT, Baxter JP, Pennington CR. A randomized controlled trial evaluating

the use of enteral nutritional supplements postoperatively in malnourished surgical patients.

Gut. 2000;46:813-818.

8. Adam S, Batson S. A study of problems associated with the delivery of enteral feed in

critically ill patients in five ICUs in the UK. Intensive Care Med. 1997;23:261-266.

9. McClave SA, Sexton LK, Spain DA. Enteral tube feeding in the intensive care unit: factors

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10. DeJonghe B, Appere-De-Vechi C, Fournier M, Tran B, Merrer J, Melchior JC, et al. A

prospective survey of nutritional support practices in intensive care unit patients: What is

prescribed? What is delivered? Crit Care Med. 2001;29:8-12.

11. Heyland DK, MacDonald S, Keefe L, Drover JW. Total parental nutrition in the critically

ill patient. A meta-analysis. JAMA. 1998;280:2013-2019.

12. Heyland DK, Montalvo M, MacDonald S, Keefe L, Su XY, Drover JW. Total parenteral

nutrition in the surgical patient: a meta-analysis. Can J Surg. 2001;44:102-111.

13. Potter J, Langhorne P, Roberts M. Routine protein energy supplementation in adults:

systematic review. BMJ. 1998;317:495-501.

14. Sandstrom R, Drott C, Hyltander A. The effect of postoperative intravenous feeding (TPN)

on outcome following major surgery evaluated in a randomized study. Ann Surg.

1993;217:185-195.

15. Beier-Holgersen R, Boesby S. Influence of postoperative enteral nutrition on postsurgical

infections. Gut. 1996;39:833-835.

16. Singh G, Ram RP, Khanna SK. Early postoperative enteral feeding in patients with

nontraumatic intestinal perforation and peritonitis. J Am Coll Surg. 1998;187:142-146.

17. Kalfarentzos F, Kehagias J, MEad N, Kokkinis K, Gogos CA. Enteral nutrition is superior

to parenteral nutrition in severe acute pancreatitis: Results of a randomized prospective

trial. Br J Surg. 1997;84:1665-1669.

18. Iovinelli G, Marsili I, Varassi. Nutritional support after total laryngectomy. JPEN.

1993;17:445-448.
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19. Moore FA, Moore EE, Jones TN, McCroskey BL, Petersen VM. TEN versus TPN

following major abdominal trauma reduced septic morbidity. J of Trauma. 1989;29:916-

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20. Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, Booth FV, Morgenstein-Wagner

TB, et al. Early enteral feeding, compared with parental, reduces postoperative septic

complications. The results of a meta-analysis. Ann Surg. 1992;216:172-183.

21. Young B, Ott L, Twyman. The effect of nutritional support on outcome from severe head

injury. J Neurosurg. 1987;67:668-676.

22. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative

total parenteral nutrition in surgical patients. N Engl J Med. 1991;325:525-532.

23. Zaloga GP, Bortenschlager L, Black KW, Prielipp R. Immediate postoperative enteral

feeding decreases weight loss and improves healing after abdominal surgery in rats. Crit

Care Med. 1992;20:115-119.

24. Mochizuki H, Trocki O, Dominioni L, Brackett KA, Joffe SN, Alexander JW. Mechanism

of prevention of postburn hypermetabolism and catabolism by early enteral feeding. Ann

Surg. 1984;200:297-310.

25. Moore EE, Jones TN. Benefits of immediate jejunostomy feeding after major abdominal

trauma - a prospetive randomized study. J of Trauma. 1986;26:874-880.

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clinical outcome. Crit Care Med. 1999;27:2799-2805.

29. Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key

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controlled clinical trials. Ann Surg. 1999;229:467-477.

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31. Hedberg A, Lairson DR, Aday LA, Chow J, Suki R, Houston S, et al. Economic

implications of an early postoperative enteral feeding protocol. J Am Diet Assoc.

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32. Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A, et al. Outcome and costeffectiveness of perioperative enteral immunonutrition in patients undergoing elective

upper gastrointestinal tract surgery. Arch Surg. 1994;134:1309-1316.

33. Senkal M, Mumme A, Eickhoff U, Geier B, Spath G, Wulfert D, et al. Early postoperative

enteral immunonutrition: Clinical outcome and cost-comparison analysis in surgical

patients. Crit Care Med. 1997;25:1489-1496.

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1146.
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Chapter 34. Prevention of Clinically Significant Gastrointestinal Bleeding in

Intensive Care Unit Patients

Daniel D. Dressler, MD

Mark V. Williams, MD

Kimberly Rask, MD, PhD

Emory University Schools of Medicine and Public Health

Background

Stress-related gastric ulceration was first described in the early 1970s,1

 and has since

received extensive study. Appreciation of the physiologic changes that promote stress-related

gastritis2-4 and general improvements in the care of critically ill patients have likely played a role

in reducing the frequency of this complication.3

 Nonetheless, the use of specific pharmacologic

agents for the prevention of stress-related gastrointestinal (GI) bleeding is increasingly promoted

as standard therapy in the ICU setting.5-8 Despite the common use of these agents, controversy

about the evidence supporting this practice remains.5,9 Because specific pharmacologic

prophylaxis for stress ulceration may increase the risk of other complications (eg, nosocomial

pneumonia10) and is associated with significant costs,11 recent efforts have focused on

delineating an appropriate definition of clinically important GI bleeding and identifying patients

who derive a clear benefit from pharmacologic prevention of this complication.

Practice Description

This chapter reviews evidence supporting the use of pharmacologic therapies for stress

ulcer and GI bleeding prophylaxis in the ICU setting. We considered the use of histamine-2

receptor blocking agents (H2-receptor antagonists) and sucralfate, a mucosal protecting agent.

Although the efficacy of aluminum- and magnesium-based antacids has been demonstrated, their

use is limited by dosing frequency and side effects.12 Proton-pump inhibitors (PPIs) and enteral

nutrition have also shown benefit in small studies, but there are yet no large randomized

evaluations.6,12,13

Prevalence and Severity of the Target Safety Problem

The risk of stress ulceration and subsequent GI bleeding depends on a patient’s

underlying illness, its severity, and related comorbidities. Using liberal criteria for assessment of

bleeding, early reports estimated the incidence of GI bleeding due to stress ulceration in ICU

patients to be as high as 5-25%.14,15 However, more recent prospective studies, using stricter

definitions of clinically significant GI bleeding and following large cohorts of patients, have

revealed more modest estimates of 0.1% in low-risk ICU patients and 2.8% in ventilated

patients.2,13,16

Opportunities for Impact

 A recent, prospectively collected database of over 7000 patients admitted to surgical and

medical intensive care units at a tertiary care center (1988-95) revealed that 59.9% of patients

received pharmacologic prophylaxis with ranitidine or sucralfate for stress ulceration.16 Another

study assessed the annual change in stress ulcer prophylaxis in nearly 3000 patients admitted to a

medical intensive care unit at a tertiary care hospital from 1993 to 1996. It found a significant

decrease in rates of prophylaxis, with a 71% rate in 1993 progressively decreasing to a 21% rate

in 1996, likely reflecting emerging evidence regarding high and low-risk populations in the
369

literature during that time.17 Identifying appropriate patients for stress ulcer prophylaxis and

avoiding its use in other cases both offer potential opportunities for improving patient safety in

the ICU.

Study Designs

Although multiple meta-analyses have reviewed the prophylaxis of GI bleeding in

critically ill patients, many were performed more than a decade ago.18-20 Since then, results of

additional randomized trials have been published. More recent, well-designed search strategies,

strict quality-scoring of literature, and rigorous adherence to criteria defining clinically

significant GI bleeding have improved the breadth and quality of literature captured, likely

making older systematic reviews less relevant. Because of these changes in quality measures as

well as overlap of information and trials from older reviews contained within more recent ones,

only those meta-analyses published within the last 5 years (and large randomized controlled

trials not included in these reviews) are included here.

A 1996 meta-analysis found 269 studies through a broad search of multiple databases and

extensive efforts to find unpublished trials.5

 Sixty-three of these met inclusion criteria. The

analysis evaluated multiple types of prophylaxis for GI bleeding, including antacids, H2-

antagonists, and sucralfate. The study authors compared each type of prophylaxis to placebo and

to each other when literature was available. The same study group then followed-up unanswered

questions from their meta-analysis with a large randomized controlled trial (RCT) of 1200

patients, comparing ranitidine to sucralfate without a placebo group.21

A more recent meta-analysis abstracted evidence from the literature to compare ranitidine

(instead of all H2-antagonists) versus placebo, and sucralfate versus placebo for GI bleed

prophylaxis in the ICU.9

 The search methods were less rigorous and the target population

narrower than the 1996 meta-analysis, but the authors claimed to assess a more clinically

relevant population and outcome.

Results from 2 prospective cohort studies that evaluated risk factors for occurrence of

clinically important GI bleeding also provide key recommendations regarding clinical

practice.2,13

Study Outcomes

Both meta-analyses and the large RCT reported outcomes of clinically important GI

bleeding and nosocomial pneumonia (Level 1). The 1996 meta-analysis and randomized trial

also evaluated overt GI bleeding and mortality. Cohort studies (Level 2) present results of

multivariate regression analyses, identifying the salient risk factors for clinically important GI

bleeding in the ICU patient.

Evidence for Effectiveness of the Practice

Table 34.1 summarizes the outcomes for the 2 meta-analyses and large RCT. The

disparity in results of the meta-analyses is partly due to differing article selection criteria. While

the 1996 analysis evaluated all H2-antagonists, the 2000 study excluded trials evaluating

cimetidine because of its virtual replacement (attributable to its undesirable side effect profile)

by ranitidine in current clinical practice.5,9 Excluding studies with cimetidine substantially

reduced the number of studies available for review. Additionally, the 1996 study evaluated

comparisons of therapies to each other as well as to placebo, while the 2000 study only

considered trials of effectiveness with a placebo control as relevant.
370

The 2000 meta-analysis found no statistically significant reduction in clinically important

GI bleeding when comparing H2-antagonist agents with placebo, or sucralfate to placebo.9

However, the 1996 study revealed a significant difference between ranitidine and placebo for

clinically important GI bleeding.5

 It was unable to demonstrate such a difference between

ranitidine and sucralfate. The results of these 2 reviews reveal discrepant findings, in large part

due to exclusion of cimetidine in the 2000 study. However, that study also included at least one

moderate-sized trial that used remarkably strict criteria for defining clinically important GI

bleeding. This factor likely contributed an element of bias towards the null result in that metaanalysis.

Furthermore, the large RCT (1998) comparing ranitidine to sucralfate, without a placebo

comparison group, revealed a statistically significant difference in the rate of clinically important

upper GI bleeding, favoring H2-antagonists.21 In this RCT the number needed to treat (NNT)

with ranitidine compared to placebo to prevent one clinically important GI bleed compared to

placebo was 47. However, no reduction in mortality or length of ICU stay was found.

Interpretation of the results of the RCT are complicated by: 1) wide confidence intervals

surrounding the relative risk estimate; 2) very small numbers of patients with clinically

important GI bleeding (ranitidine group: 10/596; sucralfate group: 23/604), only 42% of whom

had endoscopic confirmation of the source of bleed; 3) a large number of patients (70%)

receiving concomitant enteral nutrition, believed to reduce the risk of GI bleeding (see Chapter

33); and 4) unreported incidence of coagulopathy or duration of prophylaxis prior to GI

bleeding.22

The 2 large cohort studies found respiratory failure (odds ratio 15.6, p<0.001),

coagulopathy (odds ratio 4.3, p<0.001), and renal insufficiency (relative risk 1.16, p=0.023) to

be independent risk factors for predicting clinically important GI bleeding in ICU patients.2,13

Enteral nutrition had a protective effect on GI bleed outcome (relative risk 0.30, p=0.004). Even

though previous studies found a high incidence of overt GI bleeding among head trauma

patients, this was not supported by the most recent cohort study cited above, which evaluated

ventilated head trauma patients.13,23

Potential for Harm

 Table 34.2 summarizes the harm evaluated in the 2 recent meta-analyses and large RCT.

All 3 studies showed either a trend toward reduction or statistically significant reduction of

nosocomial pneumonia in sucralfate groups compared with ranitidine groups.5,9,21 The number

needed to harm (NNH) to cause one nosocomial pneumonia with ranitidine compared with

sucralfate was calculated as 21 to 34 (see also Subchapter 17.4). However, this effect was not

statistically significant in the RCT. No study demonstrated a harmful effect for ranitidine

compared to placebo.
371

Costs and Implementation

One cost-effectiveness analysis extracted relevant literature from MEDLINE between

1985 and 1995, representing 15 controlled clinical trials (Level 1).19 Assumptions made in the

analysis included equal efficacy for the H2-antagonist cimetidine and sucralfate, a baseline risk

of bleeding of 6%, and a 50% risk-reduction due to prophylaxis. The average cost per bleeding

episode averted was $1144 for sucralfate, but 6.5 times greater for cimetidine. However, low-risk

patients amassed a cost per bleeding episode averted of $103,725 compared to a cost of $279 for

very high-risk patients. Cost per bleeding episode averted increased significantly if the risk of

nosocomial pneumonia was included in the analysis.

The large RCT reported no difference in the duration of ICU stay for the group treated

with ranitidine compared with the group treated with sucralfate (9 days for each group).21

However, no placebo group was used.

Comment

Overall, the evidence available in the literature does not conclusively demonstrate that

the benefits of GI prophylaxis outweigh its risks for every patient admitted to the intensive care

unit. As refinements have been made in defining clinically important and significant episodes of

GI bleeding, the population that may reap benefit from prophylaxis has narrowed substantially.

In turn, a reduction in the use of prophylactic agents has followed. Most recent estimates reveal a

negligible incidence of clinically important stress-related GI bleeding in low-risk ICU patients

(approximately 0.1%) and a small incidence (less than 3%) in higher-risk patients. Improvements

in overall ICU care and use of enteral nutrition may be contributing to this decrease in incidence.

Although a statistical benefit of H2-antagonists compared with placebo or with sucralfate

has been shown in some studies, the overall clinical benefit of these agents has been disputed.

Some research shows a greater absolute number of nosocomial pneumonia cases related to

therapy with H2-antagonists than the benefit from reduction in GI bleeding, causing the NNH to

be potentially smaller than the NNT (see Subchapter 17.4). Furthermore, the overall cost-tobenefit ratio of prophylaxis increases dramatically in lower-risk patients, as shown in the

analysis noted above that accounted for increases in nosocomial pneumonia.21 Thus, the clear

benefit of administering H2-antagonists to prevent GI bleeding among many patients in an ICU

remains to be shown. This is partly due to variations in the definition of clinically significant

bleeding and pneumonia. Additional large trials are necessary to identify the patients who truly

derive net benefit from this practice, as published evidence does not yet support this practice for

many patients currently receiving the therapy.

At the present time, clinicians may consider use of prophylactic agents, an H2-antagonist

or sucralfate, to prevent clinically important GI bleeding in very high-risk patients admitted to

the ICU. Such patients may include those with respiratory failure, coagulopathy, renal failure,

and/or burns (the latter group has been excluded from most studies because its risk is believed to

be so great). However, the risk of pneumonia may influence clinicians to use prophylactic agents

only in patients with multiple risk factors for GI bleeding, and simply provide enteral nutrition to

others at less risk. The use of PPIs requires further study before any recommendation can be

made regarding them. Further research should focus on identifying subgroups of patients who do

derive net benefit from ranitidine or other acid-reducing agents.
372

Table 34.1. Studies evaluating effectiveness of pharmacologic prophylaxis of ICU patients

to prevent clinically significant GI bleeding*

EFFECTIVENESS

Study Study Design, Outcomes Comparison Groups Effect Size (95% CI)

Cook,

19965

Level 1A, Level 1 H2-antagonist vs. placebo

Sucralfate vs. placebo

H2-antagonist vs. sucralfate

OR 0.44 (0.22-0.88)

OR 1.49 (0.42-5.27)

OR 1.28 (0.27-6.11)

Messori,

20009

Level 1A, Level 1 Ranitidine vs. placebo OR 0.72 (0.30-1.70)

Cook,

199821

Level 1, Level 1 Ranitidine vs. sucralfate RR 0.44 (0.21-0.92)

NNT 47

* CI indicates confidence interval; NNT, number needed to treat (for benefit); OR, odds ratio;

and RR, relative risk.

Table 34.2. Studies evaluating harm (nosocomial pneumonia) due to pharmacologic

prophylaxis of ICU patients to prevent GI bleeding*

HARM

Study Study Design, Outcomes

Measured

Comparison Groups Effect Size (95% CI)

Cook,

19965

Level 1A, Level 1 Sucralfate vs. H2-antagonist OR 0.78 (0.60-1.01)

Messori,

20009

Level 1A, Level 1 Ranitidine vs. sucralfate OR 1.35 (1.07-1.70)

NNH 21

Cook,

199821

Level 1, Level 1 Ranitidine vs. sucralfate RR 1.18 (0.92-1.51)

NNH 34

* CI indicates confidence interval; NNH, number needed to harm; OR, odds ratio; and RR,

relative risk.

References

1. Lucas C, Sugawa C, Riddle J, Rector F, Rosenberg B, Walt A. Natural History and surgical

dilemma of "stress" gastric bleeding. Arch Surgery. 1971;102:266-273.

2. Cook D, Fuller H, Guyatt G, Marshall J, Leasa D, Hall R, et al. Risk factors for

gastrointestinal bleeding in critically ill patients. N Engl J Med. 1994;330:377-381.

3. Haglund U. Stress ulcers. Scand J Gastroenterol. 1990;175:27-33.

4. Shoemaker W, Bland R, PL A. Therapy of critically ill postoperative patients based on

outcome prediction and prospective clinical trials. Surg Clin North Am. 1985;65:811-833.

5. Cook D, Reeve B, Guyatt G, Heyland D, Griffith L, Buckingham L, et al. Stress ulcer

prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA.

1996;275:308-314.
373

6. Beejay U, Wolfe M. Acute gastroinestinal bleeding in the intensive care unit: the

gastroenterologist's perspective. Gastroenterol Clin North Am. 2000;29:309-336.

7. Friedman S, Manaker S, Weinhouse G. Stress ulcer prophylaxis in the intensive care unit.

In: Rose BD, ed. UpToDate. Wellesley, MA: UpToDate, Inc.; 2001.

8. ASHP Commission on Therapeutics. Therapeutic guidelines on stress ulcer prophylaxis.

Am J Health Syst Pharm. 1999;56:347-379.

9. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in

intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: metaanalysis of randomised controlled trials. BMJ. 2000; 21:1-7.

10. Ben-Menachem T, McCarthy B, Fogel R, Schiffman R, Patel R, Zarowitz B, et al.

Prophylaxis for stress-related gastrointestinal hemmorhage: a cost effectiveness analysis.

Crit Care Med. 1996;24:338-345.

11. Cook D. Stress ulcer prophylaxis gastrointestinal bleeding and nosocomial pneumonia.

Best evidence synthesis. Scand J Gastroenterol. 1995;210:48-52.

12. Hastings P, Skillman J, Bushnell L, Silen W. Antacid titration in the prevention of acute

gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients. N Engl

J Med. 1978;298:1041-1045.

13. Raff T, Germann G, Hartmann B. The value of early enteral nutrition in the prophylaxis of

stress ulceration in the severely burned patient. Burns. 1997;23:313-318.

14. Ben-menachem T, Fogel R, Patel R, Touchette M, Zarowitz B, Hadzijahic N, et al.

Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit: a

randomized, controlled, single-blind study. Ann Intern Med. 1994; 21:568-575.

15. Shuman R, Schuster D, Zuckerman G. Prophylactic therapy for stress ulcer bleeding: a

reappraisal. Ann Int Med. 1987;106:562-567.

16. Pimentel M, Roberts D, Bernstein C, Hoppensack M, Duerksen D. Clinically significant

gastrointestinal bleeding in critically ill patients in an era of prophylaxis. Am J

Gastroenterol. 2000;95:2801-2806.

17. Devlin J, Ben-Menachem T, Ulep S, Peters M, Fogel R, Zarowitz B. Stress ulcer

prophylaxis in medical ICU Patients: annual utilization in relation to the incidence of

endoscopically proven stress ulceration. Ann Pharmacother. 1998;32:869-874.

18. Tryba M. Prophylaxis of stress ulcer bleeding: a meta-analysis. J Clin Gastroenterol.

1991;3(Suppl. 2):S44-S55.

19. Lacroix J, Infante-Rivard C, Jenicek M, Gauthier M. Prophylaxis of upper gastrointestinal

bleeding in intensive care units: a meta analysis. Crit Care Med 1989;17:862-869.

20. Cook D, Witt L, Cook R, Guyatt G. Stress ulcer prophylaxis in the critically ill: a meta

analysis. Am J Med. 1991;91:519-527.

21. Cook D, Guyatt G, Marshall J, Leasa D, Fuller H, Hall R, et al. A comparison of sucralfate

and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring

mechanical ventilation. N Engl J Med. 1998;338:791-797.

22. Hinds C, Fletcher S. Ranitidine reduced clinically important gastrointestinal bleeding in

patients who required mechanical ventilation. Gut. 1999;44:10-11.

23. Burgess P, Larson G, Davidson P, Brown J, Metz C. Effect of ranitidine on intragastric pH

and stress-related upper gastrointestinal bleeding in patients with severe head injury. Dig

Dis Sci. 1995;40:645-650.

24. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for

clinically important upper gastrointestinal bleeding in patients requiring mechanical

ventilation. Crit Care Med. 1999;27:2812-2817.
374
375
376

Chapter 35. Reducing Errors in the Interpretation of Plain Radiographs and

Computed Tomography Scans

Sunil Kripalani, MD

Mark V. Williams, MD

Kimberly Rask, MD, PhD

Emory University Schools of Medicine and Public Health

Background

Misinterpretation of radiographic studies is a common source of medical error in both the

inpatient and outpatient arenas.1,2 Of particular concern is the significant number of

misinterpretations of plain radiographs and cranial computed tomography (CT) scans in

emergency departments (ED) or urgent care settings by non-radiologists.3-6 The prevalence of

this patient safety issue may result from the large volume of patients receiving these radiologic

tests, which are often done outside normal working hours when radiologists are not available to

provide an initial interpretation. This chapter focuses on practices to reduce non-radiologists’

higher rates of misinterpretation of these commonly ordered studies.

Intuitively, it would seems that institutions could minimize the number of such mistakes

by routinely having studies interpreted by the most accurate and experienced physicians, usually

radiologists. The American College of Radiology (ACR) recommends that all imaging

procedures culminate in a written, expert opinion from a radiologist or another licensed

physician specifically trained in diagnostic radiology.7,8 However, due to the associated costs,

fewer than 20% of hospitals have full-time on-site coverage by a board-certified radiologist.9

Instead, radiologists are generally available for 8 to 12 hours a day and may not provide an

interpretation until the following morning, particularly when studies are performed after normal

working hours.9

 For many routine examinations, it may be possible to delay interpretation

without harm to patients. If results are needed urgently and a radiologist is unavailable, other

physicians (eg, emergency physicians, hospitalists, neurologists) must take responsibility for the

initial interpretation.

Patient safety may be enhanced by improving the diagnostic accuracy of these physicians

or by implementing other systems to prevent initial misinterpretations from adversely affecting

patient care. Several strategies reviewed here that may be effective in reducing these errors

include educational courses to improve the diagnostic accuracy of non-radiologists, on-site

coverage by radiology residents, and mandatory subsequent reinterpretation of studies by

radiologists.

Another approach that deserves mention is to have the initial readings made by off-site

radiologists or other specialists using a teleradiology link. Teleradiology has been effective in

facilitating emergent neurosurgical consultation prior to the interhospital transfer of patients with

head injury.10-12 Teleradiology also allows rural physicians to obtain remote consults for selected

patients,13-16 which in one report led to treatment changes in 26% of cases.17 Despite

teleradiology’s impact in these two specific settings, few studies have tested its accuracy and

utility in more general circumstances.18 Teleradiology of course requires the use of digitized

rather than film-based radiographs. In two mixed case series, discrepancies of interpretation

between digitized and original radiographs occurred in approximately 10% of cases,13,14 with

significant discrepancies in 1.5-5%.19,20 For more subtle findings the sensitivity of on-screen

images may be as low as 49%,21 leading several investigators to conclude that teleradiology is
377

inferior to film interpretation for difficult cases.21-23 At present, it appears that image quality is

the major reason behind the variable performance of teleradiology. Although the ACR has

established detailed standards for equipment and image resolution,24 radiology practices often

utilize less expensive alternatives for viewing images, including personal computers.23,25,26 The

variation in practice, rapid evolution of technology, and lack of large prospective trials make it

difficult to examine teleradiology from the standpoint of patient safety. Therefore, this chapter

will not discuss teleradiology in detail; reviews can be found elsewhere.27-30

Interventions to improve the technical quality of imaging studies, such as ensuring proper

patient positioning and film exposure, are certainly important but are also outside the scope of

this chapter. Finally, although radiologists make mistakes in interpreting films,31-37 this chapter

focuses on practices to reduce the higher rate of misinterpretations made by non-radiologists.

Practice Descriptions

Training Courses

Training courses for non-radiologists are presumably common, but we could locate only

2 descriptions in the literature.38,39 Both courses concerned interpretation of cranial CT scans,

were conducted by radiologists, and targeted ED residents and faculty physicians. The training

lasted 1-2 hours and consisted of a review of neuroanatomy and a small library of CT scans. Two

continuous quality improvement initiatives were also recently described, in which radiologists

provided regular feedback to ED physicians about their radiograph interpretations.40,41

Initial Interpretations by Radiology Residents

Initial interpretation of ED films by radiology residents follows no standardized practice.

Their hours of coverage and the degree to which they interact with ED physicians vary widely.42

It is also unclear to what extent emergency physicians rely on the resident interpretations when

they are available.

Review of All Studies by Radiologists

Reinterpretation of all studies by a radiologist is already commonly used. When a

radiologist finds that a study was initially misinterpreted, the medical error has already occurred.

In this case, the safety practice concerns how the radiologist communicates the corrected

interpretation to providers in order to minimize the risk of harm to patients. The method of

communication varies among health care facilities and includes placing the interpretation in the

patient’s medical record, sending a report to the referring physician, or contacting the physician

or patient directly for more urgent concerns (see also Subchapter 42.4).7

Prevalence and Severity of the Target Safety Problem

Many investigators have focused on the prevalence of all ED readings that are discordant

with radiologists’ subsequent interpretations (with the radiologists’ interpretation assumed to be

the “gold standard”). Against this standard, ED physicians and residents misinterpret 1-16% of

plain radiographs43-51 and approximately 35% of cranial CT scans.52 However, many discordant

readings involve subtle or incidental findings that are not clinically significant (ie, they do not

affect patient management or outcome). From the standpoint of patient safety, it is the rate of

clinically significant misinterpretations and related errors in management that are of concern.

Most ED studies show that important errors in interpretation occur in 1-3% of plain

radiographs.40,43,46-51 However, one pediatric study calculated a 6.8% rate of significant
378

radiograph misinterpretation.53 The most common error is failure to recognize an extremity

fracture.43,46,51,54 Lufkin and colleagues examined the readings of 16,410 consecutive radiographs

and the effect of emergency physicians’ confidence on the accuracy of their interpretations.55

When ED physicians were confident in their interpretation, the rate of discordant readings was

1.2%. More importantly, the rate of clinically significant errors was only 0.1%.

Rates of misinterpretation are even higher for CT scans. In one study, ED residents and

attending physicians overlooked new infarcts, mass lesions, and cerebral edema, as well as

parenchymal, subarachnoid, and subdural hemorrhages.52 The rate of clinically important errors

was 20-25%, with failure to recognize a cerebral infarction the most common.52 It is unclear how

many patients had adverse outcomes as a result, but the authors estimated that less than 1% of

patients were managed inappropriately by ED staff.52 Other studies confirm that the radiographic

accuracy of non-radiologists in detecting a major cerebral infarction is poor, with

misinterpretation rates of 30-40%.56-59 This may directly impact patient outcomes since

management of suspected stroke, specifically determining eligibility for thrombolytic therapy,

requires an immediate and accurate interpretation of the CT. In addition, intraobserver and

interobserver reliability are fair to poor, with kappa (κ) values ranging from 0.41-0.20.57,59

Radiology residents have better accuracy in interpretation of cranial CT scans, though not

as high as that of certified radiologists. As part of a departmental quality control program, Lal

and colleagues found the rate of significant misinterpretations by radiology residents was 0.9%.60

Roszler et al reported moderate or major errors in 2.1% of resident interpretations of posttraumatic head CT scans.61 Wysoki and colleagues62 found that major discrepancies between the

interpretations of residents and staff radiologists occurred in 1.7% of neuroradiologic studies and

that the rate was significantly higher when CT scans were abnormal rather than normal (12.2%

vs. 1.5%). Residents missed 9% of intracranial hemorrhages and 17% of cranial or facial

fractures.

Opportunities for Impact

The accepted standard of care, supported by the ACR, calls for routine review of all

radiologic studies by a radiologist or other qualified physician in a timely fashion.8

 Given the

available data on staffing patterns,9

 we estimate that on-site radiologists are available to interpret

radiographs about half the time. Radiologists generally read any remaining studies the following

day. In academic centers, the percentage of films initially interpreted by residents may range

from 20% to 100%, and the availability of on-call residents is highly variable.42 It is also unclear

what proportion of academic and community hospitals provides radiographic training courses for

non-radiologists.

Study Designs

Few studies specifically focus on methods to reduce clinically significant

misinterpretations of radiographs and CT scans. No randomized trials have evaluated the

effectiveness of the 3 patient safety practices identified above. Table 35.1 shows 4 prospective

before-after studies (Level 2 design) of educational interventions and quality improvement

initiatives.38-41 Evidence for the other 2 strategies (initial interpretations by radiology residents

and review of all studies by radiologists) is limited to descriptive studies reporting rates of

discordant interpretations for various groups of physicians (see above).
379

Study Outcomes

Most studies reported the rate of clinically significant misinterpretations (Level 2

outcome).38,40,41,53,55,63 However, the definition of “clinically significant” was subjective and

varied among reports. One trial reported only the percentage of correct CT interpretations (Level

3), without describing the significance of specific errors.39

Evidence for Effectiveness of the Practices

Levitt and colleagues38 found a significant improvement in cranial CT scan

interpretations by ED physicians after a one-hour training course. However, there were several

limitations of this study. The intervention was not tested before implementation, raising concerns

regarding its reliability and reproducibility. Previously published research at the same institution

showed a 38.7% misinterpretation rate of cranial CT scans by ED physicians.39 Because

physicians were aware of these results, they may have engaged in their own efforts that led to

improvement in CT scan interpretation. The improvement might also be explained by significant

changes in case-mix, which was not measured. A multicenter study by Perron et al39 showed that

a reproducible educational course significantly improved residents’ ability to interpret CT scans.

However, the study is limited by possible selection bias (participation in the course was

voluntary; post-test data were obtained in only 61 of 83 subjects). Although subjects in the study

by Perron were retested after a 3-month washout period, neither course has been shown to result

in sustained improvement. Quality improvement programs such as those described by Espinosa

and Preston40,41 successfully reduced the rate of misinterpreted radiographs and number of

callbacks, respectively. Through ongoing feedback and review of misinterpreted radiographs,

Espinosa and colleagues lowered the rate of important errors from 3% to 0.3%, a relative risk

reduction of 90%. The initiative described by Preston led to a 42.9% relative reduction in

callbacks to the ED, although the absolute magnitude was less impressive (0.3% absolute risk

reduction).

We found no studies that compared the readings of ED physicians with those of

radiology residents in a real-world environment. Only one investigation compared their

diagnostic skill in an experimental situation.18 Eng and colleagues exposed 4 groups of

physicians (ED attendings, ED residents, radiology attendings, and radiology residents) to a

series of 120 radiographs and calculated their receiver operating characteristic (ROC) curves.

The radiographs were selected for their difficulty, and ED physicians had previously

misinterpreted many of them. The area under the ROC curve was 0.15 higher for radiology

faculty than for ED attendings (95% CI: 0.10-0.20) and 0.07 higher for all faculty than all

residents (95% CI: 0.02-0.12). Compared with ED faculty, radiology residents had an additional

area under the ROC curve of 0.08 (95% CI: 0.02-0.14).
380

Potential for Harm

There is a potential for both radiologists51 and non-radiologists64 to overread films (ie,

falsely identify non-existent findings), which may result in unnecessary diagnostic testing or

treatment. Since the vast majority of this literature considers the radiologist’s reading to be the

gold standard, the proportion of discrepancies in interpretation that are due to false-positive

readings by radiologists is unclear.

Costs and Implementation

Only one study reported the costs of false-positive readings by ED physicians, which

averaged $85 per false-positive radiograph.64 Given the paucity of research, it is not possible to

estimate the costs of implementing universal review of emergency films by an on-site

radiologist. Finally, no studies have measured the costs of misreads to the patient and health care

system (eg, transportation, return visits, repeat or unnecessary studies, unnecessary medications)

which could potentially offset staffing costs. The marginal costs of after-hours staffing alone

may be prohibitive, especially for low-volume sites. No information is available to estimate the

cost of establishing a high-quality teleradiology program, or of educational programs for ED

physicians or trainees.

Comment

The rates of misinterpreted radiographs and CT scans are high in many studies. Of

particular concern is the 20-25% rate of clinically significant errors in reading cranial CT scans,

even among experienced emergency physicians and neurologists. Although plain films are

correctly interpreted more than 90% of the time, even “low” error rates of 1% or less are

important given the sheer number of films.

The relative roles of ED physicians, radiology residents, certified radiologists, and other

physicians will depend on their accuracy and their cost. The literature is notable for the relative

dearth of studies of interventions to reduce radiologic misinterpretation by non-radiologists, even

though dozens of studies have documented the problem. Where radiographs must be interpreted

by non-radiologists, there is limited evidence that brief educational interventions and continuous

quality improvement programs improve diagnostic accuracy. (Chapter 54 reviews general issues

surrounding changing practice behavior through education.) It is possible that radiologists’

routine review of plain radiographs may not be cost-effective when the non-radiologist clinician

has a high level of confidence in the initial interpretation, but this has not been rigorously

established. Coverage by radiology residents may add back-up accuracy to the reading of an ED

attending, but Eng’s study was biased toward a difficult set of radiographs that had previously

been misinterpreted by emergency physicians.18 The added value of a radiology resident’s

interpretation may be much lower in actual practice.

One avenue of research that could yield effective safety practices is human resource

management. Essentially, staffing could be optimized such that specific tests could be triaged to

the individual with the highest diagnostic accuracy. This kind of intervention would require

assessment of both potential coverage gaps and the skill mix of the available labor force. A

formal protocol might be developed and tested to identify coverage vulnerabilities and develop

realistic coverage options based on measured performance of the available personnel at a

particular site. While the value of this strategy is entirely speculative, it draws on general

management science and could be explored more explicitly in health care.
381

Table 35.1. Educational interventions for non-radiologists*

Study Study Setting Intervention Study Design,

Outcomes

Results†

Levitt,

199738

14 ED physicians at a

level 2 trauma center

in California

One-hour course on

cranial CT interpretation

Level 2,

Level 2

Clinically significant

misinterpretations

decreased from 23.6% to

4.0%

(ARR 19.6%, RRR 83%)

Espinosa,

200041

ED physicians at an

academic hospital in

New Jersey, 1993-99

Training on plain

radiograph interpretation

and ongoing feedback

from radiologists about

their errors

Level 2,

Level 2

Clinically significant false

negative interpretations:

from 3% to 0.3%

(ARR 2.7%, RRR 90%)

Preston,

199840

ED physicians and

radiologists at a 150-

bed community

hospital in Louisiana,

1990-95

Continuous quality

improvement initiative

with regular review of

film discrepancies

Level 2,

Level 2

Patient callbacks to ED for

clinically significant

misinterpretation: from

0.7% to 0.4%

(ARR 0.3%, RRR 42.9%)

Perron,

199839

83 ED residents at 5

academic centers in

the southeast US,

1997-98

Two-hour course on

neuroanatomy and cranial

CT interpretation

Level 2,

Level 3

Correct interpretation of a

series of 12 CT scans:

baseline 60%; 3 months

after the course, 78%

(p<0.001 for difference)

* ARR indicates absolute risk reduction; ED, emergency deparment; and RRR, relative risk reduction.

† Results reported as change from baseline to after intervention.

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comparison of interactive and Delphi consultations. Invest Radiol 1977;12:112-115.

35. Hessel SJ, Herman PG, Swensson RG. Improving performance by multiple interpretations

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an emergency radiology facility. Radiology 1979;132:277-280.

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studies: effect of multiple reading on perception error. Radiology 1990;175:155-6.

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emergency medicine residents' recognition of intracranial emergencies on computed

tomography. Ann Emerg Med 1998;32:554-562.

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interpretations and staff review. AJR 1980;137:129-133.

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385

Chapter 36. Pneumococcal Vaccination Prior to Hospital Discharge

Scott Flanders, MD

University of California, San Francisco School of Medicine

Background

Streptococcus pneumoniae (pneumococcus) is a leading cause of serious communityacquired infections, especially pneumonia, the sixth leading cause of death in the United States.1

It causes over 50,000 cases of bacteremia and at least 500,000 cases of pneumonia annually in

the United States.1-3 Although pneumococcus is an important pathogen in meningitis, bronchitis,

and otitis media, these disease processes will not be discussed in this report.

The epidemiologic rationale for targeting pneumococcal vaccination among hospitalized

patients derives from research showing that two-thirds of patients hospitalized with serious

pneumococcal infections had been hospitalized at least once in the previous 3-5 years.4-6 One

retrospective study showed that about 60% of persons 65 years of age and older hospitalized

with pneumonia had been discharged from a hospital at least once in the prior 4 years.4

 A

prospective cohort study of patients aged ≥65 discharged from the hospital showed that the 5-

year probability for readmission with pneumonia was over 7%.4

 Hospitalization, therefore, is a

marker for patients at increased risk of developing subsequent pneumococcal infection. Despite

the scope of the problem and the appeals for action from multiple specialty societies and national

health care organizations, the vaccine is underutilized in the inpatient setting.5-7 This

underutilization has been attributed to uncertain effectiveness of the vaccine and ineffective

methods of vaccine delivery during hospitalization.

Hospital-based vaccination for patients at high risk of contracting pneumococcal

infections is part of the action plan for adult immunizations developed by the Federal Centers for

Disease Control and Prevention (CDC) and the Health Care Financing Administration (HCFA).6

It is also endorsed by the CDC’s Advisory Committee on Immunization Practices (ACIP)5, 6 and

the National Vaccine Advisory Committee. In addition, most national guidelines for the

management of patients hospitalized with community-acquired pneumonia recommend

vaccination against pneumococcus at time of discharge.1,8

Practice Description

Currently, pneumococcal vaccines contain 23 capsular polysaccharide antigens of S.

pneumoniae (23-valent vaccines). Over 88% of the serotypes that cause invasive disease in the

United States, as well as 88% of serotypes accounting for penicillin-resistant isolates, are

included in the 23-valent vaccine.2,9 Newer conjugate vaccines designed primarily to enhance the

immune response in children are not covered in this review.

The practice of hospital-based pneumococcal vaccination is recommended for patients at

increased risk for pneumococcal infection or increased risk of experiencing severe disease.

Patients ≥65 years of age, or patients with certain chronic illnesses, including chronic

cardiovascular disease, chronic pulmonary disease, diabetes, alcoholism, chronic liver disease,

and functional or anatomic asplenia, are deemed high-risk.3

 It is also recommended that all

immunocompromised patients (due to HIV infection, leukemia, lymphoma, long term steroid

use, or organ transplantation, among other causes) and any patient admitted with a diagnosis of

community-acquired pneumonia be vaccinated.1,3,8 Vaccination could occur at any time during

the hospitalization, but is often recommended at discharge.
386

Prevalence and Severity of the Target Safety Problem

The goal of pneumococcal vaccination in hospitalized patients is to reduce the morbidity

and mortality associated with pneumococcal infection, namely pneumococcal bacteremia and

pneumococcal pneumonia. The CDC estimates the annual incidence of pneumococcal

bacteremia at 15-30 cases per 100,000 population and 50-83 cases per 100,000 in persons aged

≥65.3

 A recent study of the epidemiology of invasive S. pneumoniae (ie, associated with

bacteremia) in the United States found an overall incidence of 23.2 cases per 100,000,

corresponding to 62,840 cases annually.2 The incidence among adults aged 65 and older was

59.7 per 100,000. The overall fatality rate was 10%, but patients aged 18-64 with an ACIP

indication for vaccination had a fatality rate of 12.1%. Patients ≥65 years of age accounted for

51.4% of all deaths. These figures result in national estimates of over 6000 deaths in 1998

attributed to invasive pneumococcal disease.2

The precise incidence of pneumococcal pneumonia is harder to estimate due to the poor

sensitivity and specificity of diagnostic tests for this disease. At least 25-35% of all pneumonias

are linked to S. pneumoniae, resulting in a minimum of 500,000 cases of pneumococcal

pneumonia annually. Bacteremia complicates pneumococcal pneumonia in 10-25% of cases.3

The mortality rate for all patients hospitalized with community-acquired pneumonia is estimated

at between 10-15%.1

Opportunities for Impact

Despite recommendations to routinely vaccinate eligible hospitalized patients,

pneumococcal vaccine is underutilized. The high potential impact of vaccination is borne out by

recent epidemiologic evidence. Based on 1998 projections, 76% of invasive pneumococcal

disease and 87% of deaths occur in patients who are eligible for pneumococcal vaccine.2

 In

addition, 88% of penicillin-resistant isolates during the same time period were of serotypes

included in the 23-valent vaccine.9

The vaccine is currently recommended for over 30 million persons aged ≥ 65 and over 23

million persons <65 who are at high risk.3

 In 1997 only 45% of persons 65 and over reported

ever receiving the vaccine.7

 A 12-State study of Medicare patients hospitalized with pneumonia

showed that the opportunity to provide the vaccine was missed in over 80% of patients, and only

0.4% of hospitalized elderly patients were vaccinated prior to discharge.5

 More recent data from

1999 found a hospital vaccination rate in elderly patients screened, and not already vaccinated,

of less than 9%.6

 In this same study, vaccination rates were higher for patients with a discharge

diagnosis of pneumonia (23.6%), but still far below the Public Health Service goal of 60%. Few

data are available on rates of vaccination in patients <65 years of age who are otherwise at risk

for pneumococcal infection.

In this chapter we considered two independent, but linked sets of studies: those

evaluating the effectiveness of pneumococcal vaccination and those assessing strategies to

increase vaccination rates in hospitalized patients. These two areas are reviewed separately

below.

36.1. Vaccine Effectiveness

Study Designs and Outcomes

Three meta-analyses (published in 1994,10 1999,11 and 200012) have analyzed the

effectiveness of pneumococcal vaccination in adults. The first study by Fine et al10 included 9
387

randomized controlled trials (RCTs) of vaccines (valences ranging from 6 to 17) in adults with

and without risk factors for pneumococcal infection. Results were pooled and analyzed for

effects in various subgroups with careful attention to study heterogeneity (rate differences (RD)

were reported when significant heterogeneity existed).10

The second study11 included 13 randomized and quasi-randomized studies of vaccines

with valences ≥2. Consequently, this study 11 included 2 quasi-randomized studies with vaccine

valences <6 that were excluded by Fine, but included a study by Austrian et al13 that was only

partially included in the Fine meta-analysis. Results of this second meta-analysis were reported

as pooled odds ratios; when significant heterogeneity existed, ranges were presented instead of

pooled results.11

The most recent meta-analysis identified 12 reports of 13 randomized controlled trials.12

The authors excluded 3 prior trial reports14-16 based on a predetermined decision to exclude

quasi-randomized trials. Of these 3 quasi-randomized studies, the 2 older studies14, 15 (26,000

patients) reported efficacy for the vaccine, while the more recent study (27,000 Finnish patients

over aged 65) found no efficacy for pneumococcal vaccination.16 The 13 trials included 3

reports17-19 published after 1996 that were not included in either of the prior meta-analyses.

Despite the volume of RCTs that have been published, controversy still exists as to

vaccine effectiveness in certain patient populations (high-risk, elderly), as wells as to the

vaccine’s effectiveness in reducing certain outcomes (pneumonia generally, and pneumococcal

pneumonia). Consequently, we reviewed the 1997 summary report and recommendations of the

Advisory Committee on Immunization Practices, which synthesizes multiple case-control and

cohort studies of vaccine effectiveness in high-risk patients.3

 As an additional means to evaluate

effectiveness, researchers from the CDC reported results of an indirect cohort analysis using a

national database of pneumococcal bacteremia that compared distribution of pneumococcal

serotypes causing infection in vaccinated and unvaccinated patients.20

The 3 meta-analyses reported Level 1 outcomes, including systemic pneumococcal

infection and pneumococcal pneumonia. Two of these studies report infection rates with

vaccine-type and non-vaccine-type organisms,10,11 and 2 of the 3 meta-analyses additionally

report on all-cause pneumonia, bronchitis and mortality.10,12 All studies analyze data separately

for elderly patients and high-risk patients, but the study by Hutchison et al11 differs from the

other two with respect to this part of the analysis. In this study,11 vaccine efficacy in elderly and

high-risk patients is assessed with logistic regression analysis after pooled odds ratios were

determined, in contrast to the 2 other groups who report pooled odds ratios10 and relative risk12

separately for elderly, high-risk patients. The definition of pneumococcal pneumonia varied in

many studies included in the pooled results, and in subsequent studies looking at the 23-valent

vaccine.

The indirect cohort analysis by Butler et al20 reported presumptive measures of

effectiveness based on differing rates of isolation for certain serotypes of pneumococcus in

vaccinated and unvaccinated patients (Level 2 outcome).

Evidence for Effectiveness of the Practice

The meta-analyses by Fine et al10 and Hutchison et al11 showed a protective effect of

vaccination for systemic pneumococcal disease (66% effective overall, 83% effective against

vaccine-types10 in the former; 73% effective overall, 83% effective against vaccine-types in the

latter11). Fine et al10 found the vaccine 53% effective for presumptive pneumococcal pneumonia,

but analysis for heterogeneity showed that the rate difference was not statistically significant.

The summary odds ratios for all other outcomes did not achieve statistical significance, either
388

overall or in high-risk patients (ie, patients age • 55 years, patients with one or more chronic

medical problems, and immunocompromised patients). Results for pneumococcal infectionrelated outcomes did achieve significance in low-risk patients.10

Hutchison et al found effectiveness against pneumococcal pneumonia ranging from 31%

to 76% (results were significant in 3 trials), but study heterogeneity prevented a pooled

estimate.11 Regression analysis suggested similar benefits for systemic pneumococcal infection

in elderly patients, but were inconclusive for systemic infection in chronically ill patients. For

elderly patients, the authors estimated a number needed to treat (NNT) of 2520 to prevent a

single case of pneumococcal bacteremia per year.11

The most recent meta-analysis12 reported that in 3 comparisons involving approximately

21,100 immunocompetent subjects, pneumococcal vaccination was associated with significant

reductions in the incidence of all-cause pneumonia (relative risk 0.56, 95% CI: 0.47-0.66),

pneumococcal pneumonia (relative risk 0.16, 95% CI: 0.11-0.23), pneumonia deaths (relative

risk 0.70, 95% CI: 0.50-0.96) and bacteremia (relative risk 0.18, 95% CI: 0.09-0.34). However,

in 10 comparisons involving over 24,000 subjects who were elderly or likely to have impaired

immune systems, the authors found no benefit to pneumococcal vaccination in terms of any

clinical outcome of interest.12 While the relative risk for pneumococcal bacteremia in elderly or

high-risk patients showed a trend towards benefit, the results were not statistically significant

(relative risk 0.53, 95% CI: 0.14-1.94).

One additional publication21 has appeared since the search period covered by this most

recent meta-analysis.12 This publication represents a 6-month preliminary report from a

prospective comparison between 2 large cohorts (>100,000 subjects each) of Swedish patients

age • 65 years. Patients in one group received pneumococcal vaccine, influenza vaccine, or both.

The other cohort consisted of all patients from the same region and age group who chose not to

receive either of the vaccines. Among all vaccinated patients (results are pooled for

pneumococcal and influenza vaccines), hospital admission for pneumonia (including all-cause

pneumonia, pneumococcal pneumonia and invasive pneumococcal pneumonia) was significantly

reduced, and overall mortality was reduced by 57% (95% CI: 55-60%). This study design has

significant potential for bias, in that people who elect to participate in clinical studies tend to

have better outcomes independent of the treatments they receive.22-25 Nonetheless, it seems

unlikely that the results observed in this study, including a 57% reduction in all-cause mortality

over a 6-month period, could be attributable solely to a selection effect tied to patients’ decision

to participate in the study.

36.2. Vaccine Delivery Methods

Study Designs and Outcomes

Multiple studies have evaluated the effectiveness of various methods of increasing rates

of vaccination among eligible patients in both the inpatient and outpatient settings. We focused

our review on interventions relating to inpatient settings (ie, hospitals and nursing homes). Two

systematic reviews published in 1994 and 1999 evaluate multiple strategies.26, 27 The first review

identified 3 studies in hospitalized patients and one in institutionalized patients.26 The second

review includes studies identified in the first, and comments on several additional studies.27 Both

reviews grade the included studies and report pooled estimates of effectiveness. The 2 reviews

use slightly different definitions of the types of interventions, but are internally consistent with

respect to the most effective strategy, namely standing orders.
389

All studies of the effectiveness of vaccine delivery methods reported vaccination rates.

The results of several heterogeneous studies were pooled. There are few RCTs included in the

summary estimates, and most interventions were studied with a before-after analysis of

vaccination rates. Where possible, we report pooled estimates for given methods of improving

vaccine delivery, and then comment on individual studies with the most promise for improving

vaccination rates. No study of delivery methods looked at clinical outcomes.

Evidence for Effectiveness of the Practice

The systematic reviews of vaccine delivery methods with provider reminders in the

inpatient setting were associated with absolute increases in vaccination rates that ranged from

7.5%-17% (Table 36.2.1).26,27 One subsequent before-after study of chart reminders in

hospitalized patients showed that vaccination rates in eligible patients increased from 0% to

28.8%.28 The most impressive effects were seen for system-related changes, which increased

vaccination rates by 45-51%. The most effective system-related change was the implementation

of standing orders, which produced increases of 69-81% over usual care.27 Studies of pneumonia

clinical pathways (Chapter 52) have shown no effect on pneumococcal vaccination rates despite

improvements in other pathway processes.7

Potential for Harm (from pneumococcal vaccination)

Three of the studies analyzed by Fine et al10 reported data on adverse effects. Erythema

ranged from 30.6-35.1% in the vaccine group compared with 1.7-3.5% in the control group.

Fever developed in 2.0% of vaccinated patients compared with 1.2% of controls. No fatal or lifethreatening adverse events occurred. Moore et al12 report that in one study, in addition to

increased rates of fever, vaccine recipients were more likely to experience a swollen or sore arm.

There is the theoretical concern that patients vaccinated in the hospital may have an increased

chance of being inappropriately revaccinated if they are unaware of their prior vaccination status

(due to illness, etc.) or are being cared for by a physician other than their primary care doctor. A

recent study compared the safety of the vaccine in patients receiving a first vaccination and

patients receiving re-vaccination 5 years after their prior dose. There was an increase in selflimited local reactions with re-vaccination (RR 3.3, 95% CI: 2.1-5.1), but no serious adverse

reactions were reported.29 Few data address rates of adverse reactions in hospitalized patients

vaccinated at discharge who receive re-vaccination earlier than 5 years after their prior dose.

Finally, the recent study in Ugandan HIV-infected adults showed trends toward increased

rates of invasive pneumococcal disease, all pneumococcal events, and a statistically significant

increase in all-cause pneumonia (hazard ratio 1.89, 95% CI: 1.1-3.2) among vaccine recipients.19

This study calls into question the utility of giving pneumococcal vaccine to HIV-infected

individuals.

Costs and Implementation

The cost-effectiveness of hospital-based pneumococcal vaccination is difficult to

determine in light of the debate over how effective the vaccine is in reducing pneumococcal

outcomes in at-risk populations. A cost-effectiveness analysis of vaccination for all elderly

patients in the United States recently demonstrated a wide range of possible outcomes that

depended on assumptions of vaccine effectiveness and duration of protection.30 Base-case

estimates showed that vaccination was cost saving at $8.27, and gained 1.21 quality-adjusted

days of life per person vaccinated. Factoring in the future medical costs of survivors, vaccinating

all patients ≥ 65 years of age would cost $9600 per quality-adjusted life year under the most
390

optimistic assumptions about vaccine effectiveness, and $51,661 per quality-adjusted life-year

under worst-case assumptions.30 A recent systematic review of pneumococcal vaccine costeffectiveness by authors from the Cochrane Vaccines Field concluded that there is too much

variability in assessments of cost-effectiveness (largely attributed to uncertainty over vaccine

effectiveness) to reach any firm conclusions.31 The authors called for a moratorium on all

economic modeling until completion of a Cochrane review of pneumococcal vaccine

effectiveness.

Comment

Pneumococcal vaccine is effective in reducing invasive disease in low-risk patients. It

appears effective in reducing invasive disease in the elderly and high-risk patients based on

results of one meta-analysis, multiple case-control studies, and a CDC serotype prevalence

study. Importantly however, 2 meta-analyses failed to demonstrate a significant benefit of the

vaccine for any outcomes in elderly or other high-risk patients. The vaccine appears efficacious

in non-bacteremic disease (pneumococcal pneumonia) in low-risk patients, and one metaanalysis suggests a protective effect against pneumococcal pneumonia in the elderly,11 but the

others do not.10,12 No study has demonstrated reductions in mortality. Thus, in the population

most likely to be targeted by hospital-based immunization programs (elderly, high-risk) vaccine

efficacy remains inconclusive. If it is assumed to be effective in reducing the incidence of the

most serious outcome in this population (pneumococcal bacteremia), best estimates suggest a

very large NNT (>2500).

Increasing antibiotic resistance, the aging of the US population and the major burden of

pneumococcal disease among adults and elderly patients make increasing vaccination rates an

obvious goal if, in fact, the vaccine is effective. The evidence supports system changes (in

particular, the use of standing orders) as the best method of increasing vaccine rates in eligible,

hospitalized patients. Though such rates can be increased, available data regarding vaccine

efficacy raise doubts about the overall utility of both local and national initiatives aimed at

increasing the rates of pneumococcal vaccination at hospital discharge. Early enthusiasm

explains the large number of national pneumococcal vaccine initiatives, however available data

on effectiveness provide only modest support for these initiatives.
391

Table 36.1. 1. Pneumococcal vaccine efficacy*

Study Description Study Design,

Outcomes

Results (95% Confidence Interval)

Meta-analysis of 9 RCTs.

Vaccine valences 6-17,

included international

studies, high- and lowrisk patients.10

Level 1A,

Level 1

Definitive pneumococcal pneumonia:

OR 0.34 (0.24-0.48), RD 4/1000 (0-7)

Definitive pneumococcal pneumonia, vaccine types:

OR 0.17 (0.09-0.33), RD 8/1000 (1-16)

Presumptive pneumococcal pneumonia:

OR 0.47 (0.35-0.63), RD 13/1000 (-21 to 47)

All cause pneumonia: OR 0.90 (0.77-1.04)

Mortality: OR 1.02 (0.90-1.14)

Stratified results show no benefit in any outcome for highrisk patients.

Meta-analysis of 13 RCTs

and “quasi-randomized”

trials. Vaccine valences 2-

17, includes international

trials, high and low-risk

patients.11

Level 1A,

Level 1

Systemic infection, vaccine type: OR 0.17 (0.09-0.31)

Systemic infection all types: OR 0.27 (0.13-0.49)

All cause pneumococcal pneumonia: OR range 0.24-0.69,

results significant in 3 studies

Pneumococcal pneumonia, vaccine types:

OR range 0.08-0.85, 8 of 9 studies showed reduced risk,

results significant in 6 studies.

Stratified results show benefit in elderly, mixed results in

chronically ill.

Meta-analysis of 13 RCTs

including three recent

trials published after the

last meta-analysis.12

Level 1A,

Level 1

All pneumonias:

Healthy (H), RR 0.56 (0.47-0.66), NNT 29 (24-36);

Elderly, High Risk (E) RR 1.08 (0.92-1.27)

Pneumococcal pneumonias:

H, RR 0.16 (0.11-0.23), NNT 38 (33-45);

E, RR 0.88 (0.72-1.07)

Pneumococcal bacteremia:

H, RR 0.18 (0.09-0.34), NNT 32 (26-44);

E, (3 trials and only 927 pts), RR 0.53 (0.14-1.94)

Pneumonia-related death:

H, RR 0.70 (0.50-0.96), NNT 213 (114-1660);

E, RR 0.93 (0.72-1.20)

Six-month preliminary

results report from

prospective comparison

between cohort of

100,242 Swedish patients

age • 65 years who

received pneumovax,

influenza vaccine, or

both, and patients from

the same region and age

group who chose not to

participate in the study.21

Level 2,

Level 1

Results pool all vaccinated patients.

Hospital admission for all cause pneumonia reduced by 29%

(24-34), for pneumococcal pneumonia 36% (3-58),

invasive pneumococcal pneumonia 52% (1-77).

Overall mortaliy reduced by 57% (55-60)

* OR indicates odds ratio; RD, risk difference; and RR, relative risk.
392

Table 36.2. 1. Vaccine delivery

 Study Description Study Design,

Outcomes

Results

Systematic review of studies

from 1980-1997 of methods to

increase vaccination rates.

Multiple vaccines (eg,

pneumococcal, influenza,

hepatitis) delivered in

multiple inpatient and

ambulatory settings were

reviewed, but this summary

focuses on pneumococcal

vaccine in hospitalized

patients

Level 2A-3A

Vaccination rates

(Level 2)

Provider reminders increased vaccination rates

by 17% (pooled absolute increases for all

vaccines in all settings, with a range of 1-

67%).

Standing orders achieved a 51% mean absolute

increase in vaccination rates (range 30-81%)

for all vaccine types; pneumococcal

vaccination in particular the increases ranged

from 69% to 81% (in hospital setting and longterm care facility).

Systematic review of studies

from 1979-1992. Multiple

vaccine types in multiple

settings.

Level 2A-3A

Vaccination rates

(Level 2)

Provider-oriented interventions resulted in a

7.5% increase in vaccination coverage (3.4-

11.6%)

System-oriented interventions resulted in a

45.5% increase in vaccination coverage (95%

CI: 37.2-53.7%).

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10. Fine MJ, Smith MA, Carson CA, Meffe F, Sankey SS, Weissfeld LA, et al. Efficacy of

pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. Arch

Intern Med. 1994;154:2666-2677.

11. Hutchison BG, Oxman AD, Shannon HS, Lloyd S, Altmayer CA, Thomas K. Clinical

effectiveness of pneumococcal vaccine. Meta-analysis. Can Fam Physician. 1999;45:2381-

2393.

12. Moore RA, Wiffen PJ, Lipsky BA. Are the pneumococcal polysaccharide vaccines

effective? Meta-analysis of the prospective trials. BMC Fam Pract. 2000;1:1.

13. Austrian R. Surveillance of pneumoccal infection for field trials of polyvalent

pneumococcal vaccines. Bethesda MD. 1980: National Institute of Health; 1980. NIH

Publication DAB-VDP-12-84. Contract No 1A13257. 1-59.

14. MacLoed CM, Hodges RG, Heidelberger M, Bernhard WG. CM MacLoed, RG Hodges, M

Heidelberger, WG Bernhard: Prevention of pneumococcal pneumonia by immunization

with specific capsular polysaccharides. J Exp Med. 1945;82:445-465.

15. Kaufman P. Pneumonia in old age: active immunization against pneumonia with

pneumococcus polysaccharide, results of a six year study. Arch Intern Med. 1947;79:518-

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16. Honkanen PO, Keistinen T, Miettinen L, Herva E, Sankilampi U, Laara E, et al.

Incremental effectiveness of pneumococcal vaccine on simultaneously administered

influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons

aged 65 years or older. Vaccine. 1999;17:2493-2500.

17. Koivula I, Sten M, Leinonen M, Makela PH. Clinical efficacy of pneumococcal vaccine in

the elderly: a randomized, single-blind population-based trial. Am J Med. 1997;103:281-

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Pneumococcal polysaccharide vaccine efficacy. An evaluation of current

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395
396

Chapter 37. Pain Management

Erica Brownfield, MD

Emory University School of Medicine

Approximately 23 million people undergo surgery each year in the United States.1

Despite pharmacologic interventions, at least 40-50% of postoperative patients report inadequate

pain relief.2

 In addition, the practice of withholding analgesics due to fear of masking

symptomatology and delaying diagnosis is still widespread in many emergency rooms and acute

care settings. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and

the Agency for Health Care Policy and Research (AHCPR) have established guidelines for the

appropriate assessment and management of pain in general and postoperatively. Yet efforts to

educate clinicians as to appropriate pain management, particularly in emergency departments

(ED) and following surgery, have lagged behind the available evidence.

We have taken the point of view that untreated pain represents a patient safety problem.

This chapter reviews pain management techniques and interventions in 4 domains: use of

analgesics in patients with acute abdominal pain, the use of acute pain services, prophylactic

antiemetics during patient-controlled analgesia therapy, and non-pharmacologic interventions for

postoperative pain.

Subchapter 37.1. Use of Analgesics in the Acute Abdomen

Background

The use of analgesics in patients with acute abdominal pain has traditionally been

condemned. The 1987 edition of Cope’s Early Diagnosis of the Acute Abdomen states “though it

may appear crude, it is really prudent to withhold morphine until a reasonable diagnosis has been

made and a plan of action formulated.”

1

 The most recent edition of Cope’s Early Diagnosis of

the Acute Abdomen (1996) begins to question this long-accepted dogma, but still states that

analgesia medication should be given only after a “responsible surgeon” takes a thorough history

and performs a thorough physical examination.3

 As patients with acute abdominal pain are rarely

evaluated by a surgeon within the first few hours of presentation, it seems inappropriate and

inhumane to withhold pain medication if this practice is not supported by evidence.

Practice Description

Prescribing analgesics to patients with acute abdominal pain is infrequently done. When

prescribed, dosages and routes vary, from intramuscular to intravenous morphine in 5 to 10 mg

increments, or 0.1 mg/kg of body weight. Although JCAHO and AHCPR have established

guidelines for the appropriate assessment and management of pain in general and

postoperatively, neither addresses pain management in patients with acute abdomens. Therefore,

the traditional practice of withholding analgesia in this setting has not been seriously challenged.

Prevalence and Severity of the Target Safety Problem

According to the National Center of Health Statistics, there were 100,385,000 total visits

to US emergency departments in 1998. The most frequent principal reason for visits was

stomach or abdominal pain (5.9 million).4

 Despite studies suggesting that the early

administration of pain medication is safe and does not interfere with, and may actually facilitate,

the ability to make a correct diagnosis, recent surveys of emergency room physicians and
397

surgeons indicate that the majority withhold analgesics in patients presenting with an acute

abdomen. Wolfe et al2 surveyed 443 emergency medicine physicians and found that although

85% believe that the conservative administration of pain medication did not change important

physical findings, 76% choose not to give an opiate analgesic until after the examination by a

surgeon. Graber et al5 surveyed 131 practicing surgeons in Iowa and found 67% agreed that pain

medications interfere with diagnostic accuracy, and 82% cited their concerns about diagnostic

accuracy when deciding to withhold pain medication.

Opportunities for Impact

Limited data suggest that the number of patients with acute abdominal pain who actually

receive pain relief before surgical evaluation is small. Therefore, by educating providers in

appropriate pain management for these patients, the potential impact in emergency departments

across the country is large.

Study Designs

Five prospective randomized controlled trials (Level 1) were evaluated. Four of the 5

used a double-blind design. In each study, patients were randomly assigned to receive opiate

analgesia or placebo, and evaluated pre- and post-intervention for pain using variations of visual

analog scales (Table 37.1.1).

Study Outcomes

All 5 studies evaluated the effects of analgesia on pain relief (Level 1), and diagnoses and

treatment decisions (Level 2) in patients with acute abdominal pain. Two studies evaluated the

effects of analgesia on physical examination findings and one evaluated the effects of analgesia

on the diagnostic performance of ultrasonography in patients with acute abdominal pain (Level

3).

Evidence for Effectiveness of the Practice

All 5 studies showed that provision of analgesia decreased pain more than it decreased

localization of tenderness. None of the 5 studies indicate that the practice of providing early

analgesia is harmful. Specifically, no study found compromises in diagnosis or treatment of the

acute abdomen after increasing the use of analgesia.

Potential for Harm

The traditional belief that analgesic use in patients with acute abdominal pain may mask

signs and symptoms, delay diagnosis, and lead to increased morbidity and mortality was not

supported in these studies. All 5 studies analyzed diagnostic or management errors that occurred

in each group.

Attard et al6

 found no difference in localization of physical signs, and no difference in the

surgeon’s diagnostic confidence or management decision (to operate or to observe) between the

2 groups (opioids vs. placebo). The decision to operate or to observe was incorrect in 2 patients

in the opioid group (4%) and in 9 patients in the placebo group (18%). The surgeon’s initial

diagnosis one hour after the injection was incorrect in all of these patients. These same 2 patients

in the opioid group were incorrectly diagnosed as having non-specific abdominal pain when first

assessed, but the diagnosis was subsequently changed and both patients had an inflamed

appendix removed within 24 hours of admission. Neither appendix was perforated. There were

no deaths or side effects from the injection for either group.
398

LoVecchio et al7 documented changes in localization of physical examination findings

and differences in diagnosis between patients receiving opioid analgesia and placebo. The use of

opioids was associated with some change in tenderness and localization in half the patients but

led to no delays in care or eventual morbidity. The emergency department diagnosis differed

from the final discharge diagnosis in 4 of the 49 total patients. One such patient had received

placebo and 3 had received high-dose morphine (no significant difference). There was no delay

in outcome or time to treatment in any patient.

Zoltie8

 demonstrated that 17/134 (12%) of those receiving opioids had altered physical

signs. Of the 50 patients (out of 288 in the total opiate and placebo groups) whose signs changed

during the evaluation, the most common change (n=32) was alteration in bowel sounds. The

remaining 18 had altered sites of tenderness, in most cases a migration of a large region to a

smaller, more precise area. In no case was the diagnosis altered by a change in physical signs. To

the contrary, the correct diagnosis was facilitated in several cases, particularly in the 18 cases

where the site of pain changed.

Vermeulen et al9

 also found that the use of opioids did not change the appropriateness of

the surgeons’ decision making. Among female patients, the decision to operate was appropriate

more often in the opioid group, but the difference between this group and the placebo group was

not statistically significant. In male patients and overall, opiate analgesia did not influence the

appropriateness of the decision. The appropriateness to discharge patients without surgery was

100% in both groups. No patient who had left the hospital after 24 hours of observation without

surgery was readmitted or operated on at another local hospital. The study also assessed the

impact of analgesia on the accuracy of abdominal sonography. For diagnosis of appendicitis,

ultrasound had lower sensitivity (71.1%) and higher specificity (65.2%) in the opioid group than

in the placebo group, 80.6% and 53.8%, respectively.

Similarly, Pace et al10 found 3 diagnostic or management errors in each group (out of 35

morphine and 36 control patients). The use of opioids did not alter the physicians’ ability to

evaluate accurately and treat patients appropriately.

Costs and Implementation

The costs associated with implementing appropriate analgesic practice for patients with

acute abdominal pain are limited to physician education programs and the cost of the analgesia

and associated monitoring. There were no cost outcomes reported in any of the 5 studies.

Comment

From the available evidence, we conclude that appropriate use of analgesics in patients

with acute abdominal pain effectively decreases pain and does not interfere with diagnosis or

treatment. Recent surveys suggest many physicians believe conservative administration of pain

medication does not interfere with diagnosis and treatment of patients with acute abdominal

pain. Despite this recognition, the gap between understanding and practice remains large, and

abdominal pain is often undertreated.
399

Table 37.1.1. Randomized controlled trials of analgesia in patients with acute abdominal

pain*

Study Study Participants;

Intervention Outcomes Results†

Zoltie, 19868 268 adults with acute

abdominal pain

admitted to a hospital in

the UK; sublingual

buprenorphine vs.

placebo

Level 1 Pain better after 1 hour: 64/134 vs. 59/122 (p=NS). Only

6/32 (19%) patients who received no tablet reported pain

was better after 1 hour

Change in physical signs after 1 hour: 22/134 (16%) vs.

24/122 (20%); when site of tenderness changed, it usually

was resolution of a large region to a smaller, precise area

In no case was the diagnosis altered by a change in

physical signs

Attard,

19926

100 selected adults

admitted with clinically

significant abdominal

pain; intramuscular

papaveretum vs.

placebo

Level 1 Pain score: 3.1 vs. 8.3 (p<0.0001)

Tenderness score: 5.1 vs. 8.3 (p<0.0001)

Diagnostic or management errors: 2/50 vs. 9/50 (p=0.05)

Pace, 199610 75 patients with acute

abdominal pain at a US

military emergency

department; morphine

Level 1 Improvement in pain‡: 3.9±2.8 vs. 0.8±1.5 (p<0.01)

Accuracy of provisional diagnosis: no difference between

groups

Diagnostic or management errors: 3/35 vs. 3/26 (p=NS)

LoVecchio,

19977

49 adults with acute

abdominal pain and

peritoneal signs (“acute

abdomen”) admitted to

the emergency

department of a tertiary

care hospital in NY;

intravenous morphine

vs. placebo

Level 1 Pain after 15 minutes: subjective and objective

improvement with morphine (p<0.005) but not with

placebo (p• 0.05)

Significant change in physical exam with regard to

tenderness and localization: 16/32 vs. 1/16 (p<0.005)§

Initial and final diagnosis differed in 4 patients (morphine

3, placebo 1) but there was no delay in outcome or time to

treatment (by retrospective chart review)

Vermeulen,

19999

340 adults with pain in

the right lower part of

the abdomen at a

university hospital

emergency department;

intravenous morphine

vs. placebo

Level 1 Pain after approx. 45 minutes: significantly reduced with

placebo and, to a greater extent, with morphine (p<0.001)

Ultrasound had lower sensitivity (71.1% vs. 80.6%,

p<0.05) and higher specificity (65.2% vs. 53.8%, p<0.05)

in patients who received morphine.

The negative predictive value of US was significantly

lower in female patients who received morphine rather

than placebo. Other changes in predictive value did not

achieve statistical significance.

Opiate analgesia did not significantly influence the

appropriateness of the decision to operate

* NS indicates not statistically significant.

† Results are reported as intervention group vs. control group.

‡ Pain was measured on visual analog scale; larger values represented greater pain relief.

§ Change in tenderness from 2 or more quadrants to one and the loss of rebound tenderness or

vice versa were considered significant
400

References

1. Silen W. Cope’s early diagnosis of the acute abdomen, 17th ed. New York: Oxford

University Press; 1987.

2. Wolfe JM, Lein DY, Lenkoski K, Smithline HA. Analgesic administration to patients with

an acute abdomen: a survey of emergency medicine physicians. Am J Emerg Med

2000;18:250-153.

3. Silen W. Cope's Early Diagnosis of the Acute Abdomen. 19th ed. New York: Oxford

University Press; 1996.

4. Centers for Disease Control and Prevention. NCHS-FASTATS-Emergency Department

Visits. Available at: http://www.cdc.gov/nchs/fastats/ervisits.htm. Accessed April 1, 2001.

5. Graber MA, Ely JW, Clarke S, Kurtz S, Weir R. Informed consent and general surgeons’

attitudes toward the use of pain medication in the acute abdomen. Am J Emerg Med

1999;17:113-116.

6. Attard AR, Corlett MJ, Kidner NJ, Leslie AP, Fraser IA. Safety of early pain relief for

acute abdominal pain. BMJ 1992;305:554-556.

7. LoVecchio F, Oster N, Sturmann K, Nelson LS, Flashner S, Finger R. The use of

analgesics in patients with acute abdominal pain. J Emerg Med 1997;15:775-779.

8. Zoltie N, Cust MP. Analgesia in the acute abdomen. Ann R Coll Surg Engl 1986;68:209-

210.

9. Vermeulen B, Morabia A, Unger PF, Goehring C, Skljarov I, Terrier F. Acute appendicitis:

influence of early pain relief on the accuracy of clinical and US findings in the decision to

operate – a randomized trial. Radiology 1999;210:639-643.

10. Pace S, Burke TF. Intravenous morphine for early pain relief in patients with acute

abdominal pain. Acad Emerg Med 1996;3:1086-1092.

Subchapter 37.2. Acute Pain Services

Background

The concept of an acute pain service (APS) was first reported in 1988. Its genesis was the

recognition of the problems wrought by inadequate postoperative pain management and

appreciation that acute pain may prolong recovery or precipitate complications. Over the past 15

years, in the United States and worldwide, hospitals have created multidisciplinary acute pain

services, with specially trained staff and resources geared toward providing up-to-date

techniques and education. The APS creates a framework in which postoperative pain can be

managed more effectively, hopefully leading to less discomfort and fewer postoperative

complications.

Practice Description

An APS attempts to bridge the gap between physicians, nurses and patients to coordinate

pain management. The roles of the APS are 1) educating patients, 2) educating nurses and

physicians, 3) selecting appropriate analgesic techniques for different situations, 4) preparing

guidelines for different analgesic regimens, 5) helping to manage acute pain problems, and 6)

performing quality control activities.

Most acute pain services in the United States are anesthesiology-based. The

comprehensive pain management teams usually consist of staff anesthesiologists, resident
401

anesthesiologists, specially trained nurses, pharmacists and physiotherapists. Some services are

nurse-based rather than anesthesia-based.

Prevalence and Severity of the Target Safety Problem

Approximately 50% of patients undergoing surgery do not receive adequate pain relief.1

Failure to appropriately treat pain stems from lack of knowledge and skills on the part of health

care providers and those responsible for health care system management, and insufficient patient

education. The “safety” problem targeted by the practice of implementing an APS is

postoperative pain and morbidity.

Opportunities for Impact

Approximately 34-44% of hospitals in Europe2,3 and most major institutions in the United

States4

 have organized APSs. In general, few smaller hospitals have an APS. Therefore, there are

many opportunities to institute acute pain services in hospitals.

Study Designs

Six articles were reviewed for this chapter. All are observational studies; one with a

control, 5 without controls. All 6 studies looked at the intervention of an acute pain service in

patients undergoing surgery (Table 37.2.1).

Study Outcomes

Three of the 6 studies assessed postoperative pain (Level 1). Two of the 6 studies

assessed adverse effects and safety (Level 2) and one assessed knowledge and attitudes,

perceived adequacy of patients’ pain relief and the effect on staff workload and relationships.

Evidence for Effectiveness of the Practice

All 3 studies that assessed postoperative pain scores found improvements. Bardiau et al2

showed that differences in pain score were most pronounced (around 50%) in patients

undergoing vascular, maxillofacial, gynecologic, oral and urologic surgeries. Gould et al5

showed a reduction in median visual analog scores for pain during relaxation, movement and

deep inspiration. Tighe et al6

 showed a significant improvement in patient perception of pain

relief after introduction of an APS.

Schug and Torrie7

 found no complications resulting in sustained morbidity or mortality

when anesthesiology-based APS provided postoperative pain relief. Potentially severe

complications (without sequelae) occurred in 0.53% of patients. In one study by Tsui et al,8

 1.8%

of patients developed respiratory complications (bradypnea, hypercapnia, oxygen desaturation),

1.2% developed hypotension, and 28.8% and 15.1%, respectively, developed nausea and

vomiting. None suffered long-term sequelae.

Although the postoperative setting is a logical place for acute pain services, they may

also be useful in patients who experience pain as part of a disease process. Although used more

for managing chronic conditions such as cancer and low back pain, acute pain services are also

gaining popularity in treating hospitalized patients with pain due to a medical condition. There

are no rigorous trials of APSs as they are used for medical patients.

Potential for Harm

Fragmentation of care (ie, lack of continuity between the anesthesiologist performing

preoperative evaluation and anesthesiologist providing postoperative pain control, or
402

fragmentation of care among multiple physicians) and decreased attention by the physician-ofrecord may result in problems from the intervention. However, no studies have examined these

concerns.

Costs and Implementation

Although none of the studies directly examined costs of implementing an acute pain

service, one study estimated that an APS might be cost-effective.6

 Some data suggest that a

nurse-based APS may be more cost-effective than an anesthesiologist-based APS, although there

are no formal analyses of this supposition.9

Principal obstacles to implementing such acute pain services include financial

constraints, the challenges of educating newly qualified doctors regarding pain management, and

the complexity of published guidelines.9

Comment

Studies of APSs are mostly observational, measuring postoperative pain, adverse

outcomes and staff knowledge and attitudes regarding its implementation. Although these studies

indicate that acute pain services can improve postoperative pain without endangering patient

safety, no formal recommendation can be made in the absence of high quality, systematic

reviews of the benefits, costs and feasibility of implementing these services.
403

Table 37.2.1. Studies of acute pain services in postoperative pain management*

Study Setting Study Design,

Outcomes Results

1304 patients in the pre-APS

inception phase and 671

patients after its implementation

undergoing various surgeries in

a university teaching hospital2

Level 3, 

Level 1

Significant reduction of all pain indicators

after APS inception (p<0.0001); major

improvement (>50%) in patients

undergoing vascular, maxillofacial,

gynecologic, urologic and oral surgeries

2035 patients undergoing

various surgical operations at a

university hospital5

Level 3, 

Level 1

Reduction in mean pain from 45 (95% CI:

34-53) to 16 (95% CI: 10-20) after APS

1518 patients undergoing

various surgeries at a district

general hospital6

Level 3, 

Level 1

Significant reduction of pain (p<0.0001)

after APS

2509 patients under APS care at

a tertiary referral teaching

hospital; 1759 received

systemic analgesia, 590

epidural; 160 other techniques8

Level 3, 

Level 2

Side effects were unusual (1.8%

respiratory, 1.2% hypotension, 28.8%

nausea, 15.1% vomiting)

3016 patients treated by an APS

for postoperative pain7

Level 3, 

Level 2

0.53% potentially severe adverse reactions

and no severe complications

48 staff members (36 nurses, 12

house officers) working in two

surgical units10

Level 3, 

Level 3

Two-thirds of staff thought APS

decreased their workload; perception of

patient pain relief significantly better in

APS unit

* APS indicates acute pain service; CI, confidence interval.
404

References

1. AHCPR. Acute pain management: operative or medical procedures and trauma, part 1. Clin

Pharm 1992;11:309-331.

2. Bardiau FM, Braeckman MM, Seidel L, Albert A, Boogaerts JG. Effectiveness of an acute

pain service inception in a general hospital. J Clin Anesth 1999;11:583-589.

3. Hall PA, Bowden MI. Introducing an acute pain service. Br J Hosp Med 1996;55:15-17.

4. Ready LB. How many acute pain services are there in the US and who is managing patientcontrolled analgesia? Anesth 1995;82:322.

5. Gould TH, Crosby DL, Harmer M, Lloyd SM, Lunn JN, Rees GAD, Roberts DE, Webster

JA. Policy for controlling pain after surgery: effect of sequential changes in management.

BMJ 1992;305:1187-1193.

6. Tighe SQ, Bie JA, Nelson RA, Skues MA. The acute pain service: effective or expensive

care? Anaesth 1998;53:382-403.

7. Schug SA, Torrie JJ. Safety assessment of postoperative pain management by an acute pain

service. Pain 1993;55:387-391.

8. Tsui SL, Irwin MG, Wong CML, Fung SKY, Hui TWC, Ng, KFJ, Chan WS, O’Reagan

AM. An audit of the safety of an acute pain service. Anaesth 1997;52:1042-1047.

9. Rawal N. Ten years of acute pain services – achievements and challenges. Reg Anesth Pain

Med 1999;24:68-73.

10. McLeod GA, Davies HTO, Colvin JR. Shaping attitudes to postoperative pain relief: the

role of the acute pain team. J Pain Symptom Manage 1995;10:30-34.

Subchapter 37.3. Prophylactic Antiemetics During Patient-controlled Analgesia Therapy

Background

Nausea and vomiting are common side effects of patient-controlled analgesia (PCA) with

opioids. When severe, nausea and vomiting may limit a patient’s tolerance of PCA. Giving

antiemetics prophylactically has been suggested as a way to prevent PCA-associated nausea and

vomiting.

Practice Description

No study has definitively determined the best prophylactic antiemetic in patientcontrolled analgesia. Prophylactic treatments that have been used include droperidol, 5-HT3

receptor antagonists (ondansetron, tropisetron), clonidine, promethazine, hyoscine, propofol and

metoclopramide. Prophylactic antiemetics have been given both at the induction of anesthesia

and at the end of surgery. A relatively new approach to minimizing nausea and vomiting

associated with PCA involves the addition of an antiemetic to PCA, so that the patient receives

both analgesic and antiemetic with each PCA demand dose.

Prevalence and Severity of the Target Safety Problem

The incidence of postoperative nausea and vomiting has varied widely (from 8 to 92%)

among studies.1

 There is no evidence that the incidence of nausea and vomiting with PCA is any

different than that with intramuscular opioids. In patients receiving PCA, 57-90% report nausea

and 27-40% report vomiting. There appears to be no clear advantage to using one opioid over

any others in PCA in terms of postoperative emesis.
405

Opportunities for Impact

The degree to which prophylactic antiemetics are used in routine practice with PCA is

unknown.

Study Designs

Tramer and Walder2

 conducted a systematic search for randomized trials (MEDLINE,

Embase, Cochrane library, reference lists, hand-searching, no language restriction) that

compared prophylactic antiemetics with placebo or no treatment in patients receiving

postoperative PCA with opioids. Their review identified 14 placebo-controlled trials with

different regimens of droperidol, ondansetron, hyoscine transdermal therapeutic system,

tropisetron, metoclopramide, propofol and promethazine. One PCA delivered tramadol; all

others delivered morphine.

Both relative risk and number needed to treat were calculated. To estimate the frequency

of drug-related adverse effects, the relative risk and the number needed to harm were calculated.

Study Outcomes

The main end point for efficacy was prevention of emetic events (Level 1). The incidence

of emetic events with active treatments (experimental event rate) and with placebo or no

treatment (control event rate) was extracted. Nausea, vomiting, and “any emetic event” (nausea,

vomiting, or nausea and vomiting) were extracted from each trial. Data on drug-related adverse

effects (Level 2) were extracted as well.

Evidence for Effectiveness of the Practice

Without antiemetic drugs, the incidence of nausea averaged 43% (range 22-80%),

vomiting 55% (45-71%), and any emetic event 67% (54-87%). At 24 hours postoperatively, the

cumulative incidence of nausea and vomiting in patients not receiving any antiemetic treatment

added to their PCA-morphine was approximately 50%.

The best-studied antiemetic was droperidol. It was added to morphine-PCA in 6 placebocontrolled trials involving 642 patients. Droperidol 0.017-0.17 mg/mg of morphine (0.5-11 mg/d

droperidol) was significantly more effective (p=0.04) in preventing nausea than placebo, without

evidence of dose-responsiveness. Compared with placebo, the number needed to treat with

droperidol to prevent nausea was 2.7 (95% CI: 1.8-5.2) and to prevent vomiting was 3.2 (95%

CI: 2.3-4.8).

The second most frequently reported drugs were 5-HT3 receptor antagonists

(ondansetron, tropisetron). Their effect on vomiting was satisfactory, with numbers needed to

treat of approximately 5 compared with placebo. There was no evidence of any antinausea effect.

Promising results were shown with some of the other interventions (clonidine,

promethazine). However, the limited numbers of patients studied did not generate sufficient

evidence to make a recommendation.
406

Potential for Harm

With placebo, the absolute risk of minor adverse events (sedation, drowsiness and

dizziness or anxiety, restlessness and agitation) was 0-20%. In those trials that reported adverse

events with droperidol, doses of the antiemetic ranged from 1.2 mg to cumulative doses of 7.4

mg. There were no obvious differences in the incidence of minor adverse effects compared with

placebo with droperidol doses <4 mg. In all droperidol trials, 2 adverse effect-related study

withdrawals were documented. No extrapyramidal symptoms were documented in any trial.

Costs and Implementation

Costs of prophylactic antiemetics during patient-controlled analgesia have not been

evaluated. However, 1-4 doses of droperidol per day (0.25-0.5 mL q 4 h) costs $2.83-$11.32

while 1-3 doses of ondansetron per day costs $22.50-$67.50. Implementing prophylactic

antiemetics during PCA seems neither difficult nor time-consuming.

Comment

Postoperative nausea and vomiting is a common event and patients may refuse to

continue PCA because of these side effects. Prophylactic droperidol appears to decrease such

side effects. Of 100 patients who have droperidol added to their PCA pump with morphine, 30

who would have vomited or been nauseated had they not received droperidol will not suffer

these effects.

The results of this systematic review should be confirmed, as a pooled effect size

estimated by meta-analysis must be considered provisional. Additional randomized, placebocontrolled trials assessing droperidol’s prophylactic efficacy in the morphine-PCA setting can

establish its optimal use in this clinical setting.

References

1. Woodhouse A, Mather LE. Nausea and vomiting in the postoperative patient-controlled

analgesia environment. Anaesth 1997;52:770-775.

2. Tramer MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics during

patient-controlled analgesia therapy: a quantitative systematic review. Anesth Analg

1999;88:1354-1361.

Subchapter 37.4. Non-pharmacologic Interventions for Postoperative Plan

Background

Over the past decade, increased attention has been paid to non-pharmacologic

interventions in conjunction with pharmacologic interventions to treat postoperative pain. The

Agency for Health Care Policy and Research’s (AHCPR) 1992 Clinical Practice Guideline on

Acute Pain Management recommends that preoperative preparation includes educating patients

concerning pain control. The Guidelines specifically state that management of postoperative pain

may include cognitive-behavioral interventions, such as relaxation, distraction, and imagery.1

Nonetheless, non-pharmacologic interventions can only be considered beneficial if postoperative

pain is effectively decreased.
407

Practice Description

Non-pharmacologic interventions typically fall into 3 categories: health care information,

skills teaching and psychosocial support.2

 Health care information includes information on

preparation for surgery, timing of procedures, functions and roles of health care providers, selfcare responsibilities, and pain/discomfort information. Skills teaching includes coughing,

breathing and bed exercises, hypnosis, cognitive reappraisal and relaxation exercises. Relaxation

strategies include such techniques as the modified Jacobson method, Flaherty and Fitzpatrick

jaw relaxation, relaxation tapes, tapes with structured breathing, muscle relaxation and pleasant

imagery, and cognitive relaxation. Psychosocial support includes identifying and alleviating

concerns, providing reassurance, problem solving with the patient, encouraging questions and

increasing frequency of support.

Prevalence and Severity of the Target Safety Problem

The safety problem targeted by the practice of non-pharmacologic interventions is

postoperative pain. At least 40-50% of postoperative patients report inadequate pain relief,

despite pharmacologic interventions.3

 Postoperative pain can have deleterious psychological and

physiologic consequences that contribute to patient discomfort and longer recovery periods, and

may compromise outcomes.1

 It also consumes greater health care resources.

Opportunities for Impact

Non-pharmacologic interventions are increasingly used in management of postoperative

pain, although the exact proportion of patients receiving such interventions is unknown.

Study Designs

We identified 7 meta-analyses of studies evaluating the effectiveness of nonpharmacologic interventions on postoperative pain. Two of these meta-analyses evaluated

various non-pharmacologic interventions for the management of acute pain. Devine2 conducted a

meta-analysis of 191 studies looking at psychoeducational care (including all 3 intervention

categories above) for adult surgical patients. Sindhu3 conducted a meta-analysis including 49

randomized controlled trials looking at non-pharmacologic nursing interventions (preoperative

education/information, relaxation, music, imagery, biofeedback, multidisciplinary approaches

and others) for the management of acute pain. AHCPR1

 conducted a systematic search of nondrug intervention studies on postoperative pain management. One hundred forty studies were

included and formal meta-analysis of 3 was performed. The American Society of

Anesthesiologists Task Force on Pain Management, Acute Pain Section4

 performed a systematic

search for acute pain management in the perioperative setting. Two hundred thirty-three articles

were used in the formal meta-analysis; the number of articles regarding education of patients was

not reported. Good5

 performed a systematic search of trials evaluating the effects of relaxation

and music on postoperative pain. Suls and Wan6

 performed a systematic search of trials

evaluating the effects of sensory and procedural information on coping with stressful medical

procedures and pain. Seers and Carroll7

 performed a systematic review of various relaxation

techniques for postoperative pain relief. Table 37.4.1 lists the 7 articles and briefly describes

their salient features.
408

Study Outcomes

All studies reported postoperative pain (Level 1) as a primary outcome measure. Other

outcomes, such as recovery time, psychological distress, and opioid intake were reported in some

cases (Level 1).

Evidence for Effectiveness of the Practice

The extensive literature covered by the meta-analyses suggested beneficial effects of

psychoeducational care, education and instruction of patients, music and relaxation techniques

(Table 39.5.1). The 2 meta-analyses that examined opioid intake failed to show an effect of nonpharmacologic interventions in reducing postoperative opioid consumption.

Potential for Harm

One study7

 reported no adverse events in any of the trials for any of the treatment or

control groups. Otherwise, adverse consequences of non-pharmacologic interventions on

postoperative pain management were not addressed.

Costs and Implementation

Direct information on costs of non-pharmacologic interventions was not reported in these

7 studies. Devine and Cook8 found that the beneficial impact on length of stay and medical

complications rendered non-pharmacologic interventions cost-beneficial. Another review2

hypothesized that costs could potentially be decreased by non-pharmacologic interventions,

since the length of hospital stay was shortened by an average of 1.5 days (11.5%).

The most obvious direct cost of psychoeducational care is the increased staff time to

provide these services. Based on average treatment duration of 42 minutes, a comprehensive

version of the intervention would probably not take more than 1 hour per patient.8

 Less obvious

direct costs might result from staff time to plan the protocol for psychoeducational care and/or to

develop patient education materials, in-service programs or staff meetings to teach or review the

protocol, printing or purchasing patient education materials, transporting patients to group

teaching sessions, and staff time to document the level of care provided.

Comment

Effective treatment of postoperative pain continues to be a challenge. In addition to

analgesia, non-pharmacologic interventions may provide some benefit in reducing postoperative

pain. Clinicians have a wide range of options to consider when developing a comprehensive

version of non-pharmacologic care appropriate for their patients. As such interventions are low

risk and appeal to many patients, they should be explored in practice and further research.
409

Table 37.4.1. Studies of non-pharmacologic interventions for postoperative pain

Study setting; Practice

Examined

Study

Design,

Outcomes

Results*

Adult surgical patients (# not

stated), 92% in American hospitals

(45% teaching, 43% general

hospitals); health care information,

skills teaching, psychosocial

support2

Level 1-3 A,

Level 1

79-84% of studies found beneficial effects;

Average effect size values were 0.43 for

recovery, 0.38 for pain, 0.36 for psychological

distress;

Length of stay decreased 11.5%

Not reported; transcutaneous nerve

stimulation, education/instruction,

relaxation1

Level 1-3 A,

Level 1

Simple/complex relaxation techniques,

education/ instruction effective in reducing

mild-moderate pain

Not reported; education and

participation of patients and

families in pain control4

Level 1-3 A,

Level 1

Education improves pain control, reduces

adverse outcomes

Adult pts who have undergone torso

surgery (# not stated); relaxation

techniques, music5

Level 1-3 A,

Level 1

Total pain decreased in 10 of 13 studies;

Sensory pain† reduction was reported in 6 of 12

studies;

Affective pain‡ decreased in 10 of 13 studies;

Unidimensional pain decreased in 4 of 7 studies;

Observed pain decreased in 4 of 4 studies

Not reported; sensory and

procedural information

(explanations of what will be

happening and how patients can

expect to feel) 6

Level 1-3 A,

Level 1

Combination of procedural and sensory

preparation significantly better than control on

all measures; effect sizes with combination

larger than with either type of information alone

362 patients undergoing fractured

hip repair, removal of malignant

skin lesions, major elective

abdominal surgery, elective

cholecystectomy, abdominal

hysterectomy, femoral angiography;

jaw relaxation, imagery, music,

breathing, relaxation tapes7

Level 1-3 A,

Level 1

3 of 7 studies showed significant decrease in

pain sensation/pain distress in those who had

relaxation; 1 out of 5 trials showed significant

improvement in psychological outcomes; less

anxiety in relaxation group

3387 adult patients; education,

relaxation, music, imagery,

biofeedback, multidisciplinary

approach3

Level 1-3 A,

Level 1

Effect sizes ranged from 2.25 to 1.78; strong

heterogeneity

* Effect size is the standardized difference between the control and experimental groups regarding the

measure of interest in each study. Positive values indicate benefit with the intervention.

† Sensory pain refers to ability to discriminate where pain is occurring and respond appropriately.

‡ Affective pain is the sensation of pain as something unpleasant and to be avoided.
410

References

1. AHCPR Pain Management Guideline Panel. Clinicians’ quick reference guide to

postoperative pain management in adults. J Pain Symptom Manage 1992;7:214-228.

2. Devine EC. Effects of psychoeducational care for adult surgical patients: a meta-analysis of

191 studies. Patient Educ Couns 1992;19:129-142.

3. Sindhu F. Are non-pharmacological nursing interventions for the management of pain

effective? – a meta-analysis. J Adv Nurs. 1996;24:1152-1159.

4. A Report by the American Society of Anesthesiologists Task Force on Pain Management,

Acute Pain Section. Practice guidelines for acute pain management in the perioperative

setting. Anesth 1995;82:1071-1081.

5. Good M. Effects of relaxation and music on postoperative pain: a review. J Adv Nurs.

1996;24:905-914.

6. Suls J, Wan CK. Effects of sensory and procedural information on coping with stressful

medical procedures and pain: a meta-analysis. J Consult Clin Psychol 1989;57:372-33379.

7. Seers K, Carroll D. Relaxation techniques for acute pain management: a systematic review.

J Adv Nurs 1998;27:466-475.

8. Devine EC, Cook TD. Clinical and cost-saving effects of psychoeducational interventions

with surgical patients: a meta-analysis. Res Nurs Health 1986;9:89-105.
411

Section F. Organization, Structure, and Culture

Chapter 38. "Closed" Intensive Care Units and Other Models of Care for Critically Ill

Patients

Chapter 39. Nurse Staffing, Models of Care Delivery, and Interventions

Chapter 40. Promoting a Culture of Safety
412
413

Chapter 38. “Closed” Intensive Care Units and Other Models of Care for

Critically Ill Patients

Jeffrey M. Rothschild, MD, MPH

Harvard Medical School

Background

Patients in the intensive care unit (ICU) require complex care relating to a broad range of

acute illnesses and pre-existing conditions. The innate complexity of the ICU makes

organizational structuring of care an attractive quality measure and a target for performance

improvement strategies. In other words, organizational features relating to medical and nursing

leadership, communication and collaboration among providers, and approaches to problemsolving1

 may capture the quality of ICU care more comprehensively than do practices related to

specific processes of care.2

Most features of ICU organization do not exert a demonstrable impact on clinical

outcomes such as morbidity and mortality.3

 While hard clinical outcomes may not represent the

most appropriate measure of success for many organizational features, the role of “intensivists”

(specialists in critical care medicine) in managing ICU patients has shown a beneficial impact on

patient outcomes in a number of studies. For this reason, the Leapfrog Group, representing

Fortune 500 corporations and other large health care purchasers, has identified staffing ICUs

with intensivists as one of three recommended hospital safety initiatives for its 2000 purchasing

principles (see also Chapter 55).4

In this chapter, we review the benefits of full-time intensivists and the impact of “closed

ICUs” (defined below) on patient outcomes. Much of this literature makes no distinction

between improved outcomes in general and decreased harm in particular. However, given the

high mortality5

 and complication rates6-8 observed in ICUs, it seems reasonable to consider

global interventions such as organizational changes as patient safety practices.

Practice Description

The following practice definitions are synthesized from studies reviewed for this chapter.

For all of these models, the term “intensivist” refers to a physician with primary training in

medicine, surgery, anesthesiology or pediatrics followed by 2-3 years of critical care medicine

(CCM) training.

Open ICU model—An ICU in which patients are admitted under the care of an internist,

family physician, surgeon or other primary attending of record, with intensivists available

providing expertise via elective consultation. Intensivists may play a de facto primary role in the

management of some patients, but only within the discretion of the attending-of-record.

Intensivist Co-management—An open ICU model in which all patients receive

mandatory consultation from an intensivist. The internist, family physician, or surgeon remains a

co-attending-of-record with intensivists collaborating in the management of all ICU patients.

Closed ICU model—An ICU in which patients admitted to the ICU are transferred to the

care of an intensivist assigned to the ICU on a full-time basis. Generally, patients are accepted to

the ICU only after approval/evaluation by the intensivist. For periods typically ranging from one

week to one month at a time, the intensivist’s clinical duties predominantly consist of caring for

patients in the ICU, with no concurrent outpatient responsibilities.
414

Mixed ICU models—In practice, the above models overlap to a considerable extent.

Thus, some studies avoid attempting to characterize ICUs in terms of these models and focus

instead on the level of involvement of intensivists in patient care regardless of the organizational

model. This involvement may consist of daily ICU rounds by an intensivist (thus including

“closed model ICUs” and “intensivist comanagement”), ICU directorship by an intensivist

(possibly including examples of all 3 models above), or simply the presence of a full-time

intensivist in the ICU (also including examples of all 3 models.)

Intensivist models—ICU management may include all of these models. These models are

contrasted with the open ICU model, in which an intensivist generally does not participate in the

direct care of a significant proportion of the ICU patients.

Prevalence and Severity of the Target Safety Problem

ICUs comprise approximately 10% of acute care hospital beds.9 The number of annual

ICU admissions in the United State is estimated to be 4.4 million patients.10 Due to an aging

population and the increasing acuity of illness of hospitalized patients, both the total number of

ICU patients and their proportional share of hospital admissions overall are expected to grow.11

ICU patients have, on average, mortality rates between 12 and 17%.25 Overall,

approximately 500,000 ICU patients die annually in the United States. A recent review estimated

that this mortality could be reduced by 15 to 60% using an intensivist model of ICU

management.12

Young and Birkmeyer have provided estimates of the relative reduction in annual ICU

mortalities resulting from conversion of all urban ICUs to an intensivist model of management

model.10 Using conservative estimates for current ICU mortality rates of 12%, and estimating

that 85% of urban ICUs are not currently intensivist-managed, the authors calculated that

approximately 360,000 patients die annually in urban ICUs without intensivists. A conservative

projection of a 15% relative reduction in mortality resulting from intensivist-managed ICUs

yields a predicted annual saving of nearly 54,000 lives.

By only measuring ICU mortality rates, this analysis may underestimate the importance

of intensivist-managed ICUs. In addition to mortality, other quality of care outcome measures

that might be improved by intensivists include rates of ICU complications, inappropriate ICU

utilization, patient suffering, appropriate end-of-life palliative care, and futile care.

Opportunities for Impact

Currently, a minority of ICUs in the United States utilizes the intensivist model of ICU

management.13 Intensivists are even less frequently found in non-teaching and rural hospitals.

The potential impact of the intensivist model is far-reaching.

Study Designs

Among 14 studies abstracted for this chapter, 2 were systematic reviews and 12 were

original studies. One systematic review is an abstract that has not yet appeared in journal form

and does not provide cited references.12 The other systematic review evaluated 8 references, all

of which are included in this chapter.10 An additional 4 studies absent from the systematic review

are included here. These 4 studies include 2 abstracts that were published after the 1999

systematic review,14,15 and 2 studies of pediatric ICUs with intensivists.16,17

Among the original studies, 6 incorporated historical controls and 5 used a crosssectional approach. One study18 had both historical and cross-sectional components. The original

studies include 4 studies of adult medical ICUs, 6 studies of adult surgical ICUs and 2 studies of
415

pediatric multidisciplinary ICUs. Intensivist models used by the studies cited for this review

include 4 closed ICUs, 4 mixed ICUs, 3 ICUs with intensivist comanagement and one open ICU.

Several studies were excluded, including abstracts with insufficient data,19-25 unclear

distinctions in patient management between control groups and intervention (intensivist

managed) groups,26,27 intensivist models that may have important roles in future practice (eg,

telemedicine consultation with remote management) but are not yet widely available28,29 and

considerably older studies.30

Study Outcomes

Required outcomes of interest in studies chosen for this chapter were ICU mortality,

overall in-hospital mortality, or both. Some studies also included morbidity outcomes, adverse

events and resource utilization (eg, length of ICU and hospital stay), levels of patient acuity or

severity of illness (ICU utilization) and levels of high-intensity intervention usage. Studies

addressing the impact of intensivist ICU management on resource utilization without mortality

or outcome data were excluded. There are no data regarding the impact of intensivists.

Evidence for Effectiveness of the Practice

As shown in Table 38.1, most of the studies report a decrease in unadjusted in-hospital

mortality and/or ICU mortality, although this decrease did not reach statistical significance in 3

of the 14 studies.16,18,31 One study found a statistically insignificant increase in the unadjusted

mortality rates associated with the intensivist model ICU.32 This study also found that the ratio of

expected-to-actual mortality was reduced in the intensivist-model ICUs. This finding was

associated with a higher severity of illness scores in the intensivist-model ICU population. A

similar finding of significantly improved outcomes after adjusting for severity of illness and

comparing expected-to-actual mortality rates was demonstrated in one pediatric study.16 Overall,

the relative risk reduction for ICU mortality ranges from 29% to 58%. The relative risk reduction

for overall hospital mortality is 23% to 50%. These results are consistent with those of a

previous systematic review that found a 15% to 65% reduction in mortality rates in intensivistmanaged ICUs.10

Data concerning long-term survival (6 and 12 months) for patients cared for in ICUs with

and without intensivist management is not available. Differences in outcomes between closed

ICUs, mixed ICU models and co-managed ICUs are difficult to assess. Studies that have

addressed conversion from an open to a closed model did not utilize full-time intensivists in the

open model study phases.18,32-34 Therefore it is not clear to what extent improved patient

outcomes resulted only from changes in intensivists’ direct patient care and supervision.

The observational studies evaluating these practices suffer from 2 major limitations. Half

of the studies retrospectively compared post-implementation outcomes with those during an

historical control period. Because none of these studies included a similar comparison for a

control unit that remained open in both time periods, we lack information on secular trends in

ICU outcomes during the time periods evaluated. The other major limitation associated with

comparing mortality rates for ICU patients relates to differences in ICU admission and discharge

criteria under different organizational models. Under the intensivist model, patients are generally

accepted to the ICU only after approval/evaluation by the intensivist. Thus, conversion to an

intensivist model ICU may bring about changes in the ICU patient population that are

incompletely captured by risk-adjustment models and confound comparisons of mortality rates.

Moreover, these changes in ICU admitting practice may exert contradictory effects. For example,

an intensivist model ICU may result in fewer ICU admissions for patients with dismal
416

prognoses, and less futile care for patients already in the ICU. On the other hand, intensivistmanaged ICUs with stricter admission and discharge criteria may result in a greater overall

acuity of illness for the ICU patients and therefore higher mortality rates.

Potential for Harm

The potential for harm resulting from intensivist management is unclear. Concerns raised

in the literature about intensivist-managed ICUs include the loss of continuity of care by primary

care physicians, insufficient patient-specific knowledge by the intensivist,35 reduced use of

necessary sub-specialist consultations, and inadequate CCM training of residents who formerly

managed their own ICU patients.

Perhaps more worrisome is the impact that adoption of this practice would have on

physician staffing and workforce requirements. Without a substantial increase in the numbers of

physicians trained in CCM, projected increases in the ICU patient population over the next 30

years will result in a significant shortfall in the intensivist workforce.11

Costs and Implementation

These studies did not address the incremental costs associated with implementation of

full-time intensivists. Several studies have analyzed resource utilization and length of stay

associated with intensivist-managed ICUs.13,16,18,19,29,31,32,36 The results of these studies are

variable with respect to costs. Some demonstrate a decrease in ICU expenses. Others found

increased costs, likely due to the increased use of expensive technologies. Still others show little

overall cost differential. The cost-effectiveness and cost-benefit of an intensivist-model ICU

requires further study.

Comment

Outcomes research in critical care is particularly challenging for several reasons. It

typically relies on observational outcomes studies, and must account for the diversity and

complexity of variables measured and controlled for, such as patient-based, disease-based,

provider-based and therapy-based variables. Despite these challenges and limitations, the

literature fairly clearly shows that intensivists favorably impact ICU patient outcomes. What

remains unclear is which intensivist model to recommend—intensivist consultation versus

intensivist co-management versus closed ICUs. Also, we do not know the degree to which the

choice among these models depends on intensivist background – ie, medicine, anesthesiology or

surgery. Finally, because the mechanism of the benefit of intensivist models is unknown, the

degree to which this benefit can be captured by other changes in practice (eg, adoption of certain

evidence-based processes of ICU care) remains unclear.

The major incentive for clarifying these issues concerns the implications for staffing

ICUs in the future. While the evidence supports the beneficial role of full-time intensivists, the

current number of trainees is insufficient to keep pace with the expected increase in the number

of ICU patients.11 Until we are able to sufficiently increase the size and number of CCM training

programs for physician specialists, complementary solutions for meeting critical care

management demands should be considered. These might include incorporating physicianextenders such as nurse practitioners and physician assistants with specialized critical care

training, increased participation by hospitalists in care of ICU patients,37 regionalization of

critical care services,38 or providing innovative methods to extend intensivists’ expertise to

remote sites through telemedicine consultations.28 The latter practice seems particularly

promising—a recent time series cohort study found an approximately 33% decrease in severity-
417

adjusted hospital mortality and a nearly 50% decrease in ICU complications when a technologyenabled remote ICU management program was instituted in a community-based ICU.28
418

Table 38.1. Intensivist management in the care of critically ill patients*

Mortality Relative Risk

Reduction (%)

Study Setting Study

Year

ICU Type Study

Design,

Outcomes

Intensivist

Intervention

ICU Hospital

Closed ICU Model

Tertiary care, urban, teaching

hospital; patients with septic

shock; historical control33

1982-

1984

MICU Level 3,

Level 1

Closed NA 23

Teaching hospitals (n=2); two

study designs using historical

and concurrent controls18

1992-

1993

MICU Level 3,

Level 1

Closed NA Retrospective:

19 (p=NS)

Prospective:

26 (p=NS)

Tertiary care, urban, teaching

hospital; historical control32

1993-

1994

MICU Level 3,

Level 1

Closed NA -38 (p=NS)†

0/E 13‡

Tertiary care, urban, teaching

hospital; historical control34

1995-

1996

SICU Level 3,

Level 1

Closed 58 50§

Mixed ICU models

ICUs (n=16) with different

characteristics; cross-sectional16

1989-

1992

Pediatric

MICU

SICU

Level 3,

Level 1

Mixed RRR 25¶

OR 1.5**

NA

ICUs (n=39) with different

characteristics; cross-sectional.

Patients with abdominal aortic

surgery38

1994-

1996

SICU Level 3,

Level 1

Mixed NA OR 3.0§§

ICUs (n=31) with different

characteristics; cross-sectional.

Patients with esophageal

resection14

1994-

1998

SICU Level 3,

Level 1

Mixed NA RRR 73¶

OR 3.5**

ICUs (n=39) with different

characteristics; cross-sectional.

Patients with hepatic resection15

1994-

1998

SICU Level 3,

Level 1

Mixed NA RRR 81¶

OR 3.8**

Community teaching hospital;

historical control40

1992-

1994

MICU Level 3,

Level 1

Open 29 28

Co-managed ICUs

Tertiary care ICU in a teaching

children’s hospital16

1983-

1984

Pediatric

MICU

SICU

Level 3,

Level 3

Co-manage 48 (p=NS) NA

Tertiary care, Canadian teaching

hospital; historical control39

1984-

1986

SICU Level 3,

Level 1

Co-manage 52 31

Tertiary care, urban, teaching

hospital; cross-sectional

comparison (concurrent

control)31

1994-

1995

SICU Level 3,

Level 1

Co-manage NA 32 (p=NS)

* ICU indicates intensive care unit; MICU, medicalintensive care unit; Mixed, mixed intensivist model (including daily

ICU rounds by an intensivist, the presence of a full-time intensivist, open units with comanagement and closed units

with mandatory consultations or only intensivist management); NA, not available as outcome (was not evaluated); NS,

not stastically significant; and SICU, surgical intensive care unit.

† Negative value indicates an increase in relative risk of mortality.

‡ O/E is observed to expected mortality ratio based risk adjustment

§ Hospital mortality measured 30-days after discharge
419

¶ RRR is the unadjusted mortality relative risk reduction

** OR is the adjusted odds ratio of increased mortality associated without an intensivist model.
420

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423

Chapter 39. Nurse Staffing, Models of Care Delivery, and Interventions

Jean Ann Seago, PhD, RN

University of California, San Francisco School of Nursing

Background

Unlike the work of physicians, the work of registered nurses (RNs) in hospitals is rarely

organized around disease-specific populations. Rather, patients are generally grouped by age

and/or intensity of nursing care (eg, pediatrics or intensive care). Adult patients who require the

least amount of nursing care (the largest proportion of hospitalized patients), may be separated

into medical or surgical units but may also be combined on one unit. Because the work of RNs

and other nurses is organized differently than the work of physicians, this chapter explores the

literature related to nursing structure and process variables that may affect outcomes that relate

to patient safety.

Investigations of patient outcomes in relationship to nurses and their professional

responsibilities in hospitals commonly involve structural measures of care1-4

 including numbers

of nurses, number of nurse hours, percentage or ratios of nurses to patients, organization of

nursing care delivery or organizational culture, nurse workload, nurse stress, or qualification of

nurses. Less commonly, studies involve intervention or process measures of care including

studies based on the science of nursing and others using nurses as the intervention.1-5

 The use of

structural variables rather than process measures to study the impact of nursing activities reflects

the greater availability of data relating to the former (often obtainable from administrative

sources) compared with the latter (typically requiring chart review of direct observation). A

number of structural measures have received considerable attention, specifically measures of

staffing levels in the face of major cost cutting and other changes in health care over the past 15-

20 years. In 1996, the Institute of Medicine6

 reported that there were insufficient data to draw

conclusions about the relationship between nurse staffing and inpatient outcomes. However later

studies have revisited this issue, allowing us to review the literature relating patient outcomes to

various measures of nurse staffing levels, such as full time equivalents (FTEs), skill mix

(proportion of RN hours to total hours), or RN hours per patient day.

This chapter does not address patient outcomes as they relate to various “patient

classification systems” (PCSs), although the prevalence of the use of such systems deserves

mention. PCSs predict nursing care requirements at the individual patient level in order to

determine unit staffing, project budgets, define an objective measure for costing out nursing

services, and to maintain quality standards.

8

 Although PCSs are used for multiple purposes, they

are an inadequate tool for determining unit staffing on a daily or shift basis.

9-11

 In addition, there

are numerous patient classification systems

12-14

 and most are specific to one hospital or one

nursing unit. The validity and reliability of PCSs are inconsistent and the systems cannot be

compared with each other.8-10,15-28

 Thus, rather than reviewing studies that analyze various PCS

scores to patient outcomes, we review studies addressing the question of whether or not “safe

thresholds” exist for levels of nursing care.
424

Practice Description

The availability of nurses, the organization of nursing care, and the types of nursing

interventions vary by institution. Structuring nurse staffing (eg, availability of nurses,

organizational models of nursing care) and care interventions to meet “safe thresholds” could be

considered a patient safety practice. However, no studies have evaluated thresholds explicitly.

This chapter reviews the precursor evidence from observational studies about the strength of the

relationship between nursing variables and patient outcomes, so that possible safe thresholds

may be inferred. We assess evidence that relates patient outcomes to:

1) specific numbers, proportions, or ratios of nurses to patients (nurse staffing);

Nurse availability variables generally characterize the number of hours nurses

spend with patients. Typically, the time is not measured for each patient, but

rather averages are measured based on the census of nurses to patients at a

particular point in time. There are several common ways of accounting for this

nurse staffing and no standardized way to measure it (Table 39.1).

2) specific organization of nursing care delivery, nursing models of care, or

organizational culture; Organization of nursing care variables (Table 39.2)

may also include various nursing care delivery models, nursing unit or

hospital culture, or governance structures. An issue of governance that has

been studied by Aiken

29

 and others

30

 includes how much autonomy a nurse

has to make practice decisions, how much control she has over practice

decisions, how much collaboration occurs between physicians and nurse in

the organization, and communication patterns; and

3) specific nursing interventions; Although nursing interventions are frequently

studied in outpatient setting,31,32-39

 perhaps because these venues provide

nurses more flexibility to make independent decisions,

40-42

 studies in the

inpatient setting have included measures of education, training, or retraining

of nurses, providing audit data to nurses, and capturing nurse assessment of

patient outcomes.

The varieties of intevention studies require some comment. Education interventions are

popular in nursing research because they involve less risk than interventions that directly involve

patients and are more readily approved by hospitals and physicians.

43-51

 Unfortunately, some

investigators have made the assumption (which led to the failure to measure clinical outcomes)

that increasing nursing knowledge or changing a practice, such as handwashing, automatically

improves outcomes.52,46,48,53

Because a large part of a nurse’s job is assessment, investigators have used various

nursing assessments as interventions, such as fall risk assessment, pressure ulcer risk assessment,

or identification of patients at high risk for malnutrition,

55-60

 to reduce adverse events. In

multidisciplinary protocols, the nursing activity is often assessment, rather than a nursing process

or procedure.

49

Other process-oriented interventions that lack sufficiently rigorous data to evaluate here,

include specialty nurses,

61,62-65

 and interventions based on nursing science in the realm of nurse

decision making in acute care hospitals (eg, mouth care to reduce mucositis, nonpharmacutical
425

interventions to reduce pain, nausea and vomiting, increase sleep, and improve wound

healing).31,66-73

Prevalence and Severity of the Target Safety Problem

The target safety problems are patient adverse events such as mortality and morbidity.

The challenge is to create an optimum practice environment so that nurses can ideally reduce

safety problems.

Commonly studied adverse hospital events such as falls (Chapter 26), medication errors

(Part III, Section A), and pressure ulcers (Chapter 27), are often used as outcome indicators for

nursing practice.

83-90

 Less commonly studied are issues related to improving basic symptom

management (eg, symptoms related to poor sleep, nutrition, or physical activity, or anxiety, pain,

distress and discomfort caused by symptoms, or distress caused by diagnostic tests). In the last

decade there has been increasing public and legislative pressure to improve hospital

environments and address some of the heretofore ignored issues.

91-93

Opportunities for Impact

Unfortunately, there is no definitive evidence as to specific thresholds for RN or total

nursing staff hours per patient day, or nursing skill mix for various patient populations or nursing

unit types. The lack of empirical evidence has been problematic for politicians, the public and

the nursing community. Because decisions about nurse staffing do not have a scientific basis and

are instead based on economics and anecdotes, nurse executives and managers are frequently at

odds with staff nurses; especially those represented by labor unions, over staffing. Nurse

executives are charged with providing safe patient care at a responsible cost. The need to

constrain budgets by reducing nursing hours is in conflict with the needs of the unions and, some

allege, in conflict with the needs of patients.

Based in part on some limited data, New York and Massachusetts have passed legislation

requiring formulae to be developed that ensure safe patient care.95,96

 New Jersey has regulations

which state that licensed nurses shall provide at least 65% of the direct care hours and requires

an acuity system for patient classification.

97

 California Assembly Bill 394 directs the California

Department of Health Services to establish nurse-to-patient staffing ratios for acute care

hospitals by January 1, 2002. Sixteen states other than California have nurse staffing legislation

on the calendar but have not implemented ratios.

94

Staffing and ratios are items for collective bargaining and contract negotiations in some

areas.

98-104

 Registering complains about “unsafe staffing” may be the nurses’ only recourse

unless there is a negotiated agreement between the union and the hospital.

Current utilization of practices using nursing interventions to make an impact on adverse

hospital events is most likely limited due to uncertainty about effectiveness of specific

interventions. Resources necessary for conducting systematic studies of nursing care provided in

hospitals and then implementing the practices found to be helpful are scarce.

105-109

Study Designs

Searches of MEDLINE from 1990, CINHAL from 1966, documents published by the

American Nurses Association, and the Cochrane Collaboration Library identified no randomized

clinical trials or non-randomized controlled trials analyzing nurse staffing and adverse events.

The study designs for nurse availability (Table 39.3) and organization of care (Table 39.4) are
426

Level 2 or 3 designs. Mitchell et al

111

 references several randomized trials in her review article.

However, the articles mentioned used advanced practice nurses such as clinical nurse specialists,

or home care visits as the intervention.62,112,113

 The study by Jorgensen et al

114

 was set in a

hospital but the comparison was between a specialty stroke unit and a regular care unit. The

difference was between the different organization of stroke treatment, not nurse skill mix. The

studies abstracted are observational studies that are case control, cohort, before-after, or health

services research using data from large public databases.

The study designs for nurse interventions (Table 39.5) vary from Level 1 to 3. Five

studies use education of nurses as the intervention, and an additional 3 studies cover

enhancements to education efforts (ie, providing data to nurses about adverse events in their

units).

Study Outcomes

The studies of structural measures reported Level 1 or 2 outcomes, along with various

other outcomes such as length of stay, patient satisfaction or nurse satisfaction. Most of the

studies corrected for potential confounders and most adjusted outcomes based on patient acuity.

The process measure studies vary between Level 2 and 3 outcomes. The studies also often

included Level 4 outcomes, such as nurse knowledge, but these did not meet inclusion criteria.

Most of the studies used adverse events such as falls, nosocomial infection, pain, phlebitis,

medication errors or pressure ulcers as outcomes.

Evidence for Effectiveness of the Practice

Nurse Staffing

Table 39.4 summarizes the findings of studies exploring measures of nurse availability.

When measured at the hospital level, there is mixed evidence that nurse staffing is related to 30-

day mortality.30,83,115-118

 There is scarce but positive evidence that leaner nurse staffing is

associated with unplanned hospital readmission and failure to rescue.117,119-121

 There is strong

evidence that leaner nurse staffing is associated with increased length of stay, nosocomial

infection (urinary tract infection, postoperative infection, and pneumonia), and pressure

ulcers.

122-125

Results are conflicting as to whether richer nurse staffing has a positive effect on patient

outcomes. Although 530,89,118,120,129

 of the 16 studies in Table 39.3 reported no association

between richer nurse staffing and positive patient outcomes, the other 11 that report an

association tend to be more recent, with larger samples and more sophisticated methods for

accounting for confounders. These studies had various types and acuities of patients and, taken

together, provide substantial evidence that richer nurse staffing is associated with better patient

outcomes. Although the optimum range for acute care hospital nursing staffing is most likely

within these ranges, none of the studies specifically identify the ratios or hours of care that

produce the best outcomes for different groups of patients or different nursing units.

Models of Nursing Care Delivery

The 7 studies in Table 39.4 provide mixed evidence about the relationship between

organization of nursing care and patient outcomes. Aiken et al

29

 found that hospitals with

“magnet” characteristics have lower mortality in one study, but not in another,

115

 and Shortell et
427

al

30

 also does not find an association in ICUs. Seago

79

 found a reduction in medication errors

after a change to patient-focused care and Grillo-Peck et al

130

 found a reduction in falls after a

change to a RN-UAP (unlicensed assistive personnel) partner model was introduced. The 2

review articles111,131

 reported mixed results about whether nursing models, nurse surveillance or

work environment is associated with patient outcomes. Thus, the evidence is insufficient to

direct practice.

Nursing Interventions

Table 39.5 provides details about studies using nurse interventions. The first 3 studies

provide support for the idea that added education of nurses reduces infection and

thrombophlebitis. The subsequent 2 studies, however, found no difference in bloodstream

infection or medication error before and after added education. The overall evidence indicates

that using education as the sole intervention does not always change patient outcomes.

Educational interventions were related to changes in nurse practices and, in some studies, also

related to decreasing adverse events.

44,47,54

 However adding another intervention such as providing

feedback data or benchmarking results, was more likely to be associated with improved patient

outcomes,55-57

 including decreased infection rates, pressure ulcer rates, and fall rates.55-57

Potential for Harm

The potential for harm of patients associated with structural interventions such as too few

nurses has been documented.83-85,124,125

 Studies involving process interventions such as using

education of nurses, providing data to nurses, and interventions based on nursing science, seem

to have a low probability of harm, but that is as yet unknown.

Costs and Implementation

Few of the abstracted studies mentioned cost, although several measured length of stay as

an outcome variable. Pratt et al

63

 found no difference in quality of care measures using a 100%

RN skill mix and an 80% RN skill mix in 2 wards in one hospital in the United Kingdom. The

cost was less with the 80% skill mix but the nurses who worked with less experienced staff

reported an increase in workload and increase in stress. California is faced with impending

legislated minimum nurse staffing ratios in the acute care hospitals. Based on early studies,

149

 at

least 40% of California hospitals may see a negative financial effect because of the need to

increase staffing. Additionally, based on a number of predictions,150,151

 there is now, and there

will continue to be, a significant shortage of registered nurses in the US. Thus, implementing any

increase in RN staffing may be very difficult.

One investigator who provided data to nurses as the intervention related to urinary

catheter infection reported an estimated cost savings of $403,000.55

 Another investigator who

also provided data to nurses related to nosocomial pressure ulcer rates estimated implementation

costs but not cost saving.

57

 The investigator who studied adding an IV team (specialty nurses)

reported a savings of $53,000/saved life and $14,000/bloodstream infection. Using clean rather

than sterile dressings on open postoperative wounds saved $9.59/dressing with no change in rate

of wound healing. Based on these studies, it is likely that some nursing interventions can save

costs.
428

Comment

The studies evaluated in this review include only medical, surgical and ICU nursing

units. Other data from more specialized units, the outpatient setting, and those pertaining to

subsets of patients tend to mirror the findings of the evidence evaluation, and are cited in this

section alongside those abstracted and presented in the evidence tables.

The relationship of hospital environment to patient outcomes is still being debated.

However, evidence using hospital-level data indicates increasing the percentage of RNs in the

skill mix, increasing RN FTEs or hours per patient day or average daily census is associated with

decreased risk-adjusted mortality.116,131,152,153

 Other studies, also aggregating data to the hospital

level, found that increasing RN hours per patient day is associated with decreased nosocomial

infection rates,121,154

 decreased urinary tract infections, thrombosis and pulmonary complications

in surgical patients,

124

 decreased pressure ulcers, pneumonia, postoperative infection and urinary

tract infection.122,125

 Hunt

117

 found that decreasing ratios were related to increasing readmission

rates but were not related to mortality rates.

The cost of primary data collection has limited the number of studies using data

aggregated to the individual nursing unit. There is some evidence that decreased nurse-to-patient

ratios in the ICU was associated with an increase in blood stream infections associated with

central venous catheter,

126

 while an increase in agency nurses was related to other negative

patient outcomes.

156

 A study in the NICU setting found understaffing and overcrowding of

patients led to an outbreak of Enterobactor cloacae.

155

 In 42 ICUs Shortell et al. found that low

nurse turnover was related to shorter length of stay

30

; in 65 units an increase in nurse

absenteeism was related to an increase in urinary tract infection and other patient infections but

not to other adverse events.

157

 Amaravadi et al

158

 found that night nurse-to-patient ratio in ICUs

in 9 hospitals for a select group of patients who had undergone esophagectomy was not

associated with mortality but was associated with a 39% increase in length of stay and higher

pneumonia rates, reintubation rates, and septicimia rates. As noted previously, Blegan et al found

that as the percentage of RNs per total staff (skill mix) increased there was a decrease in

medication errors, decubitus ulcers, and patient complaints up to a skill mix of 85-87% RNs.83,84

In several studies, increasing skill mix was associated with decreasing falls, length of

stay, postoperative complications, nosocomial pneumonia, pressure ulcer rates, urinary tract

infection, and postoperative infection.122-125,130

 Several studies with varying sample sizes have

found skill mix to be unrelated to mortality.111,118,159,160

 Others have found skill mix to be

unrelated to treatment problems, postoperative complications, unexpected death rates, or

unstable condition at discharge

129

 and found no relationship between skill mix or nursing hours

per patient day and medication errors, falls, patient injuries, and treatment errors.

161

 In an early

study of primary (all RN) and team (skill mix) nursing care delivery models, there was no

relationship between percent of RNs and quality of care as measured by nurse report

162

 and in 23

hospitals in the Netherlands, there was no relationship between RN-to-patient ratio and incidence

of falls. 89

Although mixed, the overall evidence seems to indicate that proportion of RN hours per

total hours and richer RN-to-patient ratios likely do not affect 30-day mortality, may be
429

associated with in-hospital mortality, and are probably associated with adverse events such as

postoperative complications, nosocomial infection, medication errors, falls, and decubitus ulcers.

Based on recent work, nurse staffing was examined in “best practices” hospitals. This

included hospitals recognized by the American Nurses Association’s Magnet Hospital program,

those commended by the Joint Commission on Accreditation of Healthcare Organizations

(JCAHO), those listed in USA Today’s Top 100 Hospitals, those listed in US News and World

Report’s set of high-quality hospitals, those noted for having better than expected mortality for

heart attacks and newborn readmission rates by the Pacific Business Group on Health (PBGH),

and those recognized by the Bay Area Consumer Checkbook for high quality. There is

significant variation in nurse staffing among these best practices hospitals. The staffing data for

best practices hospitals do not consistently demonstrate that hospitals rated highly for quality of

patient care have uniformly richer staffing than do other hospitals.

74

 Because units within

hospitals vary widely in nurse staffing and outcomes, results from data aggregated to the hospital

level are difficult to interpret.

At present the literature is insufficient to make a reasoned judgment about organization

of the work environment of nurses. Further work is needed in the area of nurse interventions. If

there truly is to be an emphasis on reducing adverse events in hospitals and creating hospital

environments that promote health and healing, resources for research related to nurses and

nursing interventions must be found.
430

Table 39.1. Measures of nurse staffing

Nurse Staffing

Measure

Definition

Nurse to patient ratio Number of patients cared for by one nurse typically specified by

job category (RN, Licensed Vocational or Practical Nurse-LVN or

LPN); this varies by shift and nursing unit; some researchers use

this term to mean nurse hours per inpatient day

Total nursing staff or

hours per patient day

All staff or all hours of care including RN, LVN, aides counted per

patient day (a patient day is the number of days any one patient

stays in the hospital, ie, one patient staying 10 days would be 10

patient days)

RN or LVN FTEs per

patient day

RN or LVN full time equivalents per patient day (an FTE is 2080

hours per year and can be composed of multiple part-time or one

full-time individual)

Nursing skill (or staff)

mix

The proportion or percentage of hours of care provided by one

category of caregiver divided by the total hours of care (A 60% RN

skill mix indicates that RNs provide 60% of the total hours of care)

Table 39.2. Models of nursing care delivery

Nursing Care Delivery

Models

Definition

Patient Focused Care A model popularized in the 1990s that used RNs as care managers

and unlicensed assistive personnel (UAP) in expanded roles such as

drawing blood, performing EKGs, and performing certain

assessment activities

Primary or Total

Nursing Care

A model that generally uses an all-RN staff to provide all direct

care and allows the RN to care for the same patient throughout the

patient’s stay; UAPs are not used and unlicensed staff do not

provide patient care

Team or Functional

Nursing Care

A model using the RN as a team leader and LVNs/UAPs to

perform activities such as bathing, feeding, and other duties

common to nurse aides and orderlies; it can also divide the work by

function such as “medication nurse” or “treatment nurse”

Magnet Hospital

Environment/Shared

governance

Characterized as “good places for nurses to work” and includes a

high degree of RN autonomy, MD-RN collaboration, and RN

control of practice; allows for shared decision making by RNs and

managers
431

Table 39.3 Structural measures: availability of nurses and patient outcomes (First 11

studies showed positive associations; final 5 studies detected no significant effect)

Study Setting Study

Design,

Outcomes

Availability of

Nurses

Effect Size (coefficient, mean

differences, OR)

1. Data were collected form

1,205 consecutively admitted

patients in 40 units in 20 acute

care hospitals and on 820 nurses

in the US115

Level 3,

Level 1&3

0.8 mean nurse/

patient day with a

range of 0.5-1.5

nurses/patient day

This measure was significantly

associated with 30-day mortality

(OR .46, 95% CI: 0.22-0.98). An

additional nurse per patient day

reduces the odds of dying by onehalf.

2. All patients who developed a

central venous catheter

bloodstream infection during an

infection outbreak period

(January 1992 through

September 1993) and randomly

selected controls. Cohort study:

all SICU patients during the

study period (January 1991

through September 1993)126

Level 3,

Level 1

1.2 patient/nurse

and 20 nursing

hours per patient

day (HPPD)

1.5 patient/nurse

and 16 nursing

HPPD

2 patient/nurse and

12 nursing HPPD

There was a significant

relationship between nurse to

patient ratios and nursing hours

and central venous catheter

bloodstream infection in the SICU.

For 1.2 patients/nurse and 20

HPPD the adjusted odds ratio was

3.95 (95% CI: 1.07-14.54), 1.5

patients/nurse and 16 nursing

HPPD, 15.6 (95% CI: 1.15-211.4),

and for 2 patients/nurse and 12

HPPD, 61.5 (95% CI:1.23-3074).

3. 39 nursing units in 11

hospitals for 10 quarters of data

between July, 1993 and

December, 1995 in the US 84

Level 3,

Level 1&2

Proportion of

direct care RN

hours; total direct

care hours;

Up to 87.5% RN

skill mix

With patient acuity controlled,

direct care RN proportion of hours

was inversely associated with

medication errors (-0.525 p<0. 05),

decubiti (-0.485 p<0.05), and

complaints (-0.312, p<0.10). Total

direct care hours was positively

associated with decubiti (0.571,

p<0.10), complaints (0.471,

p<0.10), and mortality (0.491,

p<0.05). A curvilinear relationship

was found so that as RN

proportion increased, rates of all

adverse events decreased up to a

proportion of 88% RNs. Above

that level, as RN proportion

increased, the adverse outcomes

increased.
432

4. 42 inpatient units in one 880-

bed hospital in the US 83

Level 3,

Level 1&2

8.63 mean total

hours of care;

69% RN skill mix;

up to 85% skill

mix

With patient acuity controlled,

direct care RN proportion of hours

was inversely associated with

medication errors/doses (-

0.576, p<0.05) and falls (-

0.456, p<0.05). Total direct care

hours was positively associated

with medication errors/doses

(0.497, p<0.05). A curvilinear

relationship was found so that as

RN proportion increased,

medication error rates decreased

up to a proportion of 85% RNs.

Above that level, as RN proportion

increased, the medication error

increased

5. Data from hospital cost

disclosure reports and patient

discharge abstracts from acute

care hospitals in California and

New York for fiscal years 1992

and 1994125

Level 3,

Level 1&2

7.56-8.43 mean

total hours of

care/nursing

intensity weight

(NIW); 67.7% to

70.5% RN skill

mix

Total hours/NIW was inversely

associated with pressure ulcer rates

(-15.59, p<0.01). RN hours in

California, but not New York, was

inversely associated with

pneumonia (-0.39, p<0.01)

Nonsignificant association with

postoperative infection rates.

6. Data from hospital cost

disclosure reports, patient

discharge abstracts and Medicare

data from acute care hospitals in

Arizona, California, Florida,

Massachusetts, New York, and

Virginia for 1996123

Level 3,

Level 1&2

5.76 mean

licensed hours of

care/ 83.3% RN

skill mix

Skill mix was inversely associated

with pneumonia (-0.20, p<0.01),

postoperative infection (-0.38,

p<0.01), pressure ulcers (-0.47,

p<0.01), and urinary tract

infections (-0.61, p<0.01).

7. Data from hospital cost

disclosure reports, patient

discharge abstracts from acute

care hospitals in California,

Massachusetts, and New York

for 1992 and 1994122

Level 3,

Level 1&2

7.67-8.43 mean

total hours of care;

67.7-70.5% skill

mix

RN hours were inversely

associated with pneumonia (-

0.39, p<0.01), pressure ulcer rates

(-1.23, p<0.01), and postoperative

infection (-0.47, p<0.01) but not

significant for urinary tract

infections.
433

8. Data from HCFA Medicare

Hospital Mortality Information

1986 and the American Hospital

Association 1986 annual survey

of hospitals116

Level 3,

Level 1

0.9 mean

RN/ADC (average

daily census); 60%

skill mix

Controlling for hospital

characteristics, number of

RNs/ADC was not significantly

related to adjusted 30-day

mortality rate but proportion of

RNs/all nursing staff was

significantly related to adjusted

30-day mortality rate (adjusted

difference between lower and

upper fourth of hospitals -2.5, 95%

CI: -4.0 to -0.9)

9. Data from the American

Hospital Association 1986

annual survey of hospitals and

medical record reviews from

July 1987 to June 1988 in 6 large

PPOs128

Level 3,

Level 3

52.2 (Texas)-

67.6% (California)

skill mix

 Controlling for hospital

characteristics, number of

RNs/ADC was not significantly

related to problem rate but

proportion of RNs/all nursing staff

was significantly related to lower

problem rates (California lower

rates 3.58, upper rates 2.30

p<0.0001)

10. Data from the American

Hospital Association Annual

Survey of Hospitals for 1993 and

the Nationwide Inpatient Sample

from the Agency for Health Care

Policy and Research for 1993

(HCUP-3)124

Level 3,

Level 1

67.8% mean skill

mix

Proportion of RN FTEs/all nursing

FTEs was inversely related to

thrombosis after major surgery

(beta -33.22, 95% CI: -57.76 to -

8.687), urinary tract infection after

surgery (beta -636.96, 95%

CI: -852.78 to -421.15),

pneumonia after major surgery

(beta -159.41, 95% CI: -252.67 to

-66.16), and pulmonary

compromise after major surgery

(beta -59.69, 95% CI: -117.62 to

1.76).
434

11. Data were collected form

March 1 to June 7, 1986 and

included 497 patients127

Level 3,

Level 2

Adequate staffing The adequately staffed unit had

fewer complications than the

inadequately staffed unit.

12. 390 patients admitted within

1 week after stroke onset in 9

acute care hospitals in The

Netherlands. Surviving patients

were interviewed 6 months poststroke and asked about falls. Fall

and other patient data were

collected from medical records.

Ward characteristics were

provided by senior nurses. There

is complete data on 349

patients89

Level 3,

Level 2

0.04 mean

difference in nurse

to patient ratios

There was no statistical difference

in falls between case and control

groups in number of nurses or

nurse ratios on any shift. Days

(mean difference -0.06, CI: -

0.51 to 0.39); Evening (mean

difference -0.24, 95% CI: -0.97 to

0.50); Nights (mean difference

1.24, 95% CI: 0.28 to 2.20); All

shifts (mean difference 0.04, 95%

CI, -0.33 to 0.40).

13. 17,440 patients across 42

ICUs in the US30

Level 3,

Level 1-3

Mean .66

patient/nurse with

a range of 0.31-

1.31

Neither nurse to patient ratio nor

caregiver interaction was found to

be significantly associated with

risk-adjusted mortality.

14. Data were collected from

April, 1994-March, 1995 from

23 trusts (groups of hospitals) in

Scotland117

Level 3,

Level 1

Mean RN FTE

was 1.21 per

patient

There was no association between

RN FTE per occupied hospital bed

and mortality

15. Data were collected form the

American Hospital Association

Annual Survey of Hospitals in

1989-1991, the observed and

predicted 30-day post-admission

mortality for patients with a

primary diagnosis of COPD

from the HCFA Hospital

Information Reports from 1989-

1991 and the Medicare Case Mix

Index118

Level 3,

Level 1

RN FTE/100

adjusted

admissions

There was no association between

RN FTE/100 adjusted admissions

and 30-day post-admission

mortality for patients with a

primary diagnosis of COPD

16. Data from staffing and

accounting records of 60

community hospitals across the

US in 1985, hospital and nursing

unit surveys, 1981 case mix

indexes from the Federal

Register, and the Health Area

Resources File129

Level 3,

Level 3

52% RN skill mix;

33% LPN mean

nursing HPPD was

4.93

None of the staffing variables of

interest were associated with

medication errors, patient injuries,

IV administration errors, or

treatment errors.
435

Table 39.4 Structural variables: nursing organization models and patient outcomes

Study Setting Study

Design,

Outcomes

Organization

of Care/Models

Effect Size (coefficient, mean

differences, OR)

Data were collected from 39

"magnet" hospitals, which are

hospitals designated as good

places for nurses to work, and

195 nonmagnet matched

hospitals29

Level 3,

Level 1

Magnet hospitals Magnet hospitals had a 4.6% lower

adjusted Medicare mortality rates

(p=0.026, 95% CI: 0.9-9.4 fewer

deaths per 1,000)

 Data were collected form 1,205

consecutively admitted patients

in 40 units in 20 acute care

hospitals and on 820 nurses in

the US115

Level 3,

Level 1&2

Magnet hospitals

(nurse control

over practice

variable)

Nurse control over practice was

not significantly associated with

any clinical outcomes, but was

significantly associated with

patient satisfaction (coefficient

0.56 (95% CI: 0.16-97)

17,440 patients across 42 ICUs

in the US30

Level 3,

Level 1-3

Magnet hospitals

(nurse unit

culture captured

in caregiver

interaction

variable)

Caregiver interaction was not

significantly associated with

clinical outcomes, but was

significantly associated with lower

risk-adjusted length of stay (-0.16,

p<0.05) and lower nurse turnover

(-0.21, p<0.05)

Data were collected at 3 points in

time; 6 month before the

intervention, 6 months, and 12

months after the introduction of

the new model and included the

time between October 1996 to

December 199779

Level 3,

Level 2

Patient Focused

Care

There was a significant reduction

in medication errors between the

pre-model change (0.97%) and the

post-model change (0.78%,

p=0.016) and no difference in the

other measures

Data were collected 6 months

before and 6 months after the

introduction of the new model

and included the time between

January-June, 1992 and JanuaryJune, 1993130

Level 3,

Level 2

RN-UAP

Partnership

similar to Patient

Focused Care

There was a significant reduction

in falls (4.7732, p< 0.05) and no

difference in the other measures

between the pre- and postmeasures.

Review article: Pierce, 1997131 Level 3A,

Level 1&2

Nursing

Environment

There are mixed results in studies

about whether the predictor

variables related to nurses and

nursing are related to the outcomes

of interest or whether the

conceptual models being used are

incomplete.
436

Review article: MEDLINE from

1966-1996, CINAHL from 1982-

1996, Expanded Academic Index

from 1989-1996, search by

author for investigators known to

be working in the field, manual

searches of the bibliographies of

review articles and monographs

(Mitchell)111

Level 3A,

Level 1&2

Nursing

Environment

Mixed results in studies about

whether nursing surveillance,

quality of working environment,

and quality of interaction with

other professionals predict

hospitals with lower mortality.

With more sophisticated risk

adjustment, evidence suggests that

mortality and complications are

related more to patient variables

and adverse events may be more

closely related to organizational

characteristics.
437

Table 39.5 Process measures: nurse intervention and patient outcomes

Study Setting Study

Design,

Outcomes

Intervention Effect Size (coefficient, mean

differences, OR)

Data were collected from 60

hospitalized patients on 1 surgical

service in a university hospital in

Turkey between September 1996

and September 1997 44

Level 2,

Level 2&3

Added

education to

intervention

group

Positive colonization of catheter

hub was 68.6% in the control

group and 25% in the intervention

group (chi square=5.75, p<0.05);

mean positive nurse practice

scores in control group was 45.7

and 66.5 after education (p<0.05)

2 surgical and 2 medical wards in

one hospital in Sweden were

randomly assigned to either a

control or experimental group. 18

nurses on the experimental wards

and 18 nurse on the control wards;

90 patients on the experimental

wards and 39 patients on the control

wards; 112 Peripheral IVs on the

experimental wards and 60 PIVs on

the control wards47

Level 1,

Level 2&3

Added

education to

intervention

group

50% of the PIV lines in the

control group had

thrombophlebitis/complications

compared with 21% in

intervention (p<0.001); positive

association observed for nurse

practices related to care of PIV

lines was 12% in the control

group and 72% in the

experimental group; there was

complete nursing documentation

in 10% of the control group and

66% of the experimental group.

One hospital in Spain; all

nosocomial infection data between

March 1982 and December 199054

Level 3,

Level 1

Added

education to

intervention

group

Additional training was

associated with a significant

3.63% decrease (p<0.01) in

nosocomial infection rates.

One university hospital in

Washington, DC; all adult patients

with bloodstream Infections

between July 1984 and February

1994 (n=432)45

Level 3,

Level 2

Added

education

No significant difference in total

BSI rates or central line BSI rates

before, during or after the

program.

One general hospital in Illinois; all

omitted and wrong dose medication

errors between October 1992 and

March 199343

Level 3,

Level 2

Added

education

No difference in wrong dose IV

medication errors for 12 months

after training; there was a

decrease in omitted dose IV

mediation errors for 12 months

after training (p<0.01).
438

All urinary catheter-patient-days

between January 1995 and

September 1996 in 1 VA hospital55

Level 3,

Level 2

Provided

infection rate

data to nurses

Pre-intervention there were

32/1000 catheter-patient days

(95% CI: 22.9-43.7); for the 5

quarters post intervention, there

was a significant decrease

(p<0.01) in the average infection

rate (17.4/1000 catheter-patientdays (95% CI: 14.6-20.6))

compared to pre-intervention

Stanford University Hospital; all

pressure ulcers and nosocomial

pressure ulcers during 1992 through

199657

Level 3,

Level 2

Provided

nosocomial

pressure rate

data to nurses

plus added

education

After Intervention #1, total

pressure ulcer rate went from

20% to 21%; nosocomial pressure

ulcer rates went from 19% to

21%. After Intervention #2 total

pressure ulcer rates stayed at 21%

but nosocomial pressure ulcer

rates went from 21% to 13%.

One-year later, total pressure

ulcer rates were 10.9% and

nosocomial pressure rates were

8.1%.

8. Stanford University Hospital 52

bed medical surgical unit; all falls

between 1995 through 199656

Level 3,

Level 2

Provided fall

rate data to

nurses and

added

education

Pre-intervention the fall rate

ranged from 4.2 to 3.7 fall per

thousand patient days (FPTPD);

after Intervention #1 the fall rate

was 5.2 FPTPD; after

Intervention #2 the fall rate

ranged from 5.1 to 3.7 FPTPD.

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Chapter 40. Promoting a Culture of Safety

Laura T. Pizzi, PharmD

Neil I. Goldfarb

David B. Nash, MD, MBA

Thomas Jefferson University School of Medicine

and Office of Health Policy & Clinical Outcomes

Background

In a number of high hazard organizations, where the risk of error involves dire

consequences, leaders manage for safe, reliable performance. As a result, the term High

Reliability Organization has been coined to describe organizations with exemplary track records

of safety: aviation, chemical manufacturing, shipping, nuclear power production, and the

military.1-10 This concept is rooted in the analyses of errors that reveal organizational failures,

along with technical failures (related to system performance) and human limitations (related to

human behavior).11

Theories about antecedents to accidents abound but major schools of thought include

Reason’s belief that a number of latent factors embedded in organizational systems can align and

result in accidents,12-14 and Rasmussen’s approach to categorizing the different sources of error

that interact with latent factors to produce accidents.15-17 Another school of thought, developed

by Charles Perrow and first publicized shortly after the Three Mile Island nuclear accident,

Normal Accident Theory,

18,19 emphasizes the ever-present possibility of accidents in

organizations that exhibit complexity and “tight coupling” of processes and the inevitability of

accidents. Normal Accident Theory stands somewhat in opposition to High Reliability Theory,

which holds that accidents can be prevented through organizational design and management.

Scott Sagan’s analysis of the nuclear weapons industry, addressing the question of why there has

never been an ‘accidental’ nuclear war, represents a fascinating investigation of a test case for

these two schools of thought.20 Despite the obvious apparent confirmation of the High Reliability

Theory perspective (ie, such an accident has thankfully never occurred), Sagan uncovers a

surprising amount of evidence that also seems to confirm the Normal Accident perspective.*

Regardless of the underlying theory, health care is vulnerable to error. The application of

safety promotion theories utilized to positive effect in other high hazard organizations are being

considered for health care, where “accidents” tend to occur one person at a time instead of in

sweeping disasters.25

Attention to organizational issues of structure, strategy and culture may be a promising

direction for medicine. Although organizational elements are intertwined and must be aligned for

optimum performance26 this chapter focuses on the culture component, especially “safety

cultures.” Following a description of the prevailing models of culture and safety, we review

approaches that both medical and non-medical industries have used to promote a culture of

safety. On the medical side, the discussion is limited to the Veterans Health Administration’s

comprehensive safety initiative.27 On the non-medical side, specific methods other high

 

* Invited commentaries on Diane Vaughn’s in-depth analysis of the Challenger crash21 also

provide an interesting comparison between the Normal Accidents 22 and High Reliability Theory

23,24 perspectives and indicates that they are more complementary than contradictory. 
448

reliability industries have applied to promote a safety culture,4

 including a behavior-based

industry approach, are reported.28

Organizational Culture

Helmreich defines culture as “a complex framework of national, organizational, and

professional attitudes and values within which groups and individuals function.”

29 Corporate

culture is often referred to as the glue that holds an organization together, and is therefore

assumed to be a contributor to organizational performance by socializing workers in a way that

increases commitment to the goals of the entity.4,30,31 As such, it embodies the philosophy of

senior leaders, which is translated into, and affects the behaviors of employees.32 Although some

schools of thought focus on the role of leaders of an organization (board members and

executives), others note that middle management likely plays a substantial role as well,

conveying the culture to front-line workers in any organization, as evidenced by studies of the

effective use of total quality management.33 The power of culture often goes unrecognized, since

employees may assume that the dominant paradigm is simply “the way we do things here.”

29

Safety Culture

While an exact definition of a safety culture does not exist, a recurring theme in the

literature is that organizations with effective safety cultures share a constant commitment to

safety as a top-level priority, which permeates the entire organization. More concretely, noted

components include: 1) acknowledgment of the high risk, error-prone nature of an organization’s

activities, 2) blame-free environment where individuals are able to report errors or close calls

without punishment, 3) expectation of collaboration across ranks to seek solutions to

vulnerabilities, and 4) willingness on the part of the organization to direct resources to address

safety concerns.3,4,29,34-36 Based on extensive field work in multiple organizations, Roberts et al

have observed several common, cultural values in reliability enhancing organizations:

“interpersonal responsibility; person centeredness; [co-workers] helpful and supportive of one

another; friendly, open sensitive personal relations; creativity; achieving goals, strong feelings of

credibility; strong feelings of interpersonal trust; and resiliency.”

4

Culture Surveys

The aspect of organizational safety culture that may be visible or measurable is

sometimes referred to as the safety “climate,” which includes management systems, safety

systems, and individual attitudes and perceptions.32 Health care organizations are now adapting

safety culture and climate surveys from other industries to benchmark and identify potential

deficiencies in their unique safety culture. Kaiser Permanente, the oldest and largest not-forprofit health maintenance organization in the United States, has administered an executive

attitudes and beliefs survey to identify perceptions of patient safety for the purposes of planning

and measurement (written communication, February 2001, Suzanne Graham). The VA Palo Alto

Patient Safety Center of Inquiry and Stanford University’s Center for Health Policy/Center for

Primary Care and Outcomes Research are conducting a patient safety culture survey that builds

on past work by Gaba and collaborators. The survey includes items on production pressures and

safety consequences, and draws from several other sources (personal communication, June,

2001, Sara Singer). Spath provides a checklist of elements that health care managers can use to

identify which cultural elements should be addressed in order to improve safety37 (Table 40.1).

Previous work in assessing organizational culture effects on total quality management,38 and
449

organizational culture in high reliability organizations39 may also be pertinent to efforts to

measure culture and its consequences for patient safety.

Industries Outside Medicine

Promoting a culture of safety has historically been a priority for the chemical, electrical,

food processing, petroleum, plastic, and transportation industries. Since the 1930s, safety

managers within various industries have recognized that most occupational injuries have a strong

behavioral component, typically rooted in the safety culture.28 In these settings, behavior

analysis has been used as an approach to solving safety problems. Behavioral analyses typically

involve assessing upstream and downstream behaviors associated with the problem, with further

analysis as to which behaviors may be modifiable. Once relevant behaviors are identified, a

behavior change intervention is implemented, and behavioral changes are measured.

Interventions are customized, and draw upon techniques of behavior science, organizational

development, safety science, and quality. Researchers have shown associations between

behavior-based safety programs and reduced rates of accidents.

In an extensive field study of three organizations (nuclear aircraft carriers, a nuclear

power plant, and the Federal agency responsible for air traffic control) whose operations have

the potential for widespread harm, Roberts et al proposed several management processes that

“cradle” a culture of perfection.4

 One process requires distributing decision making, while

having mechanisms that allow decisions to migrate up and down the chain of command as

circumstances develop. The mechanism for localizing decision making is often extensive

training, while the approach to moving decisions to higher levels is based on management by

exception when acceptable operation is in question. Finally, these researchers suggest that both

top-level managers and local operators develop a deep understanding of their organizations, and

use this “big picture” perspective to provide intuitive judgments when situations arise.

Practice Description

Veterans Health Administration Approach

The Veterans Health Administration (VHA) has implemented a multifaceted safety

initiative, which was designed to build a culture of safety and address system failures.27 The

approach consists of 4 major elements: 1) partnering with other safety-related organizations and

affiliates to demonstrate a public commitment by leadership, 2) establishing centers to direct

safety efforts, 3) improving reporting systems, and 4) providing incentives to health care team

members and division leaders. These tactics are detailed below. In addition, several specific

initiatives were implemented to address problems, such as bar coding of medications

(Subchapter 43.1) and use of computerized medical records.

To demonstrate a public commitment to the importance of patient safety, the VHA

leadership founded the National Patient Safety Partnership, along with several major healthrelated organizations (the American Association of Medical Colleges, the American Hospital

Association, the American Medical Association, the American Nurses Association, and the

Institute for Healthcare Improvement). In addition, key senior management officials sounded the

safety message in congressional testimony.

The second part of the VHA's approach involved establishing centers dedicated to the

promotion of patient safety. The first of these was the National Center for Patient Safety, which

directs patient safety efforts for the VHA at a national level. The Director of the Center oversees

patient safety efforts for the entire VHA health system and is a recognized authority.
450

Subsequently, four Patient Safety Centers for Inquiry were funded, which are primarily

responsible for safety-related research and development. Specifically, the centers are responsible

for identifying problems in the patient care process, implementing corrective measures, and

studying effects. Currently, one of these centers is studying safety cultures in health care

organizations. Finally, the VHA's Virtual Learning Center contributes to the safety initiative by

allowing VHA facilities to share lessons learned. Additional information, such as training,

educational programs, alerts, and advisories are planned.

The third major component of the VHA's initiative involves incentives aimed at

improving safety. There are two types of incentives offered: 1) the "carrot," which is a monetary

award of up to $5000 for individuals and teams that develop approaches to improve safety

issues; and 2) the "stick," which is a performance expectation imposed on leaders to improve

patient safety. Leaders of the VHA's 22 regional networks must demonstrate involvement in

safety-promoting activities, or be subject to consequences, including possible termination of

employment. The primary objective of this incentive is to align regional and national leaders'

goals.

Last, the VHA has implemented a two-pronged system for capturing adverse events. The

first of these systems, the Patient Safety Event Registry, mandates reporting of adverse events

and “close calls” occurring within the system. Before implementing the Patient Safety Event

Registry, regional review of event cases was sporadic. After implementation, event data is

systematically shared both regionally and nationally. The second of the systems, the voluntary

reporter identity system, was developed in conjunction with the National Aeronautics and Space

Administration, and allows for anonymous event reporting. It is intended that the use of both

reporting systems will together provide a more comprehensive picture of safety management

than would be possible with one system alone.

Behavior-Based Safety Programs

Outside of medicine, the objective of behavior-based safety interventions is to reduce

incidents by managing at-risk behaviors of the organization and work teams. An approach

described by Krause and colleagues consisted of safety assessments, steering committee

formation, development of checklists of well-specified critical behaviors related to safety,

observer training regarding the critical behaviors, observation and feedback.28 These steps,

somewhat analogous to aspects of crew resource management training approaches (see Chapter

44), most likely reflect an active safety culture. The Krause study assessed the effectiveness of

behavioral safety initiatives in reducing accidents in 229 facilities in various industries, including

chemical, electrical, food, plastic, petroleum, transportation, service, and paper manufacturers.28

The study used an interrupted time series design with the participating industrial sites. Event

rates after implementation of the behavioral program were compared with the Occupational

Safety and Health Administration (OSHA) recordable illness/injury rates. Of the 229

participating sites, 73 provided necessary data (others were excluded either because they failed

to provide OSHA illness/injury rates or results of the behavioral initiative). Compared with

baseline, the behavioral initiative resulted in an average 26% improvement in targeted safety

behaviors during the first year, which rose to 69% by the fifth year.

Prevalence and Severity of the Target Safety Problem

There is no known information about the prevalence of medical error emanating from

cultural/organizational problems in health care. Culture is known to contribute to the occurrence

of errors and accidents. Its contribution relative to other causal factors is unknown, but likely to
451

vary, depending on the type of accident and work environment.3,7,29 The aviation industry

attributes its successful safety record in part to analysis of near miss and accident reports (see

Chapter 4).40-43 These types of analyses are only possible if the culture supports reporting of

errors. Culture changes may, in fact, have their greatest impact on “underground” (unreported)

errors, which are extremely difficult to quantify.

Opportunities for Impact

Although no data from ongoing surveys has yet emerged to permit us to accurately

quantify safety culture penetration, we nonetheless speculate based on anecdotal evidence that

health care organizations have plenty of room for improvement. A number of observers have

noted large-scale obstacles to promotion of safety culture within health care: a pervasive culture

of blame that impedes acknowledgment of error, and professional “silos” that offer unique

challenges to changing any universal aspect of health care, including culture.44-46

Even before the Institute of Medicine’s pivotal To Err is Human report was delivered to

the public, promoting a safety culture within health care had received widespread attention. The

Institute for Healthcare Improvement’s Web site features a report “Reducing Medical Errors and

Improving Patient Safety: Success Stories from the Front Lines of Medicine.”

47 It includes

articles about the transformation of culture at the prestigious Dana-Farber Cancer Institute after a

highly publicized chemotherapy overdose in 1994, which resulted in the death of a patient.

Another article in the same series highlighted the major steps, including cultural change, as noted

above, taken by leaders of the nation’s largest health care provider—the Veterans Affairs

Healthcare System—after fatal medical errors were reported by the media.47

Comment

Measuring the impact of culture on safety-related outcomes is challenging. Culture is a

complex and abstract construct that must be inferred from behaviors, and analysis often relies on

self-reported data.29 Research continues to develop a working model of safety culture that

permits measurement of several connected concepts: individuals’ perceptions and attitudes about

safety, individuals’ observable safety behaviors, and an organization’s safety management

system as evidenced by its policies and management styles.35 The relative impact of each of

these measures on outcomes is another layer of ongoing research.

Although some data support the effectiveness of the entire VHA initiative in improving

safety, there are no direct data supporting the effect of promoting a culture of safety. The use of

incentives to reward safety-promoting behavior and publicly demonstrating a commitment to

safety are approaches that could be applied in both large and small health care settings. The

VHA’s reporting system will likely be watched, and potentially adapted by large providers who

have inconsistent and/or insufficient reporting of safety problems at local, regional, and national

levels.

The evidence presented by Krause provides compelling support for the effectiveness of

behavior-based safety programs in a wide range of industrial settings. Although this exact

approach has not been evaluated in health care environments, its emphasis on promoting safety

culture seems applicable to patient care environments.

As noted in To Err is Human, researchers who have studied organizations with a strong

safety culture believe that it is “the most critical underlying feature of their accomplishments.”

48

Although the nature of the evidence is based on field studies and other methods not typical of

medical evidence, it is considered compelling by a number of experts from organizational and

other social sciences. At this point, promoting a culture of safety remains surprisingly
452

unexplored in health care settings, where the risks of error are high. Further research in this area

is warranted, though the threshold for evidence may need a different yardstick than is typically

applied in medicine (Chapter 2).

Acknowledgments

The authors are grateful to Mr. Marcus Moore of Behavioral Science Technology, Inc.

for providing information related to industrial safety programs. We would also like to thank Dr.

Kasey Thompson, Director of the American Society of Health-System Pharmacy’s Center for

Patient Safety, and Mr. Mark Thomas, Director Of Pharmacy at Children’s Hospital in

Minneapolis for their suggestions and insight on cultural safety issues.
453

Table 40.1. Checklist of elements that contribute to a patient-safe environment

All people acknowledge that top management provides essential patient safety improvement leadership.

The organization has clearly defined patient safety polices.

All people can explain the organization’s patient safety policies.

All people are involved in developing patient safety goals, and everyone can explain desired

results and measures.

All people are actively involved in identifying and resolving patient safety concerns.

All people can explain how their personal performance affects patient safety.

All people believe they have the necessary authority and resources to meet their

responsibilities for patient safety

Patient safety performance for all people is measured against goal, clearly displayed, and

rewarded.

A comprehensive review of patient safety is conducted annually, and there is a process in

place that drives continuous improvement.

Regular workplace hazard analyses are conducted to identify patient safety improvement

opportunities. The results are used to make changes in patient care activities.

All people are empowered to correct patient safety hazards as they are identified.

A comprehensive system exists for gathering information on patient safety hazards. The

system is positive, rewarding, and effective, and people use it.

All people are fully aware of patient incident trends, causes, and means of prevention.

All injury-producing patient incidents and significant “near misses” are investigated for root

cause, with effective preventive actions taken.

All people who operate patient care equipment are trained to recognize maintenance needs

and perform or request timely maintenance.

All people know immediately how to respond to an emergency because of effective planning,

training, and drills.

Facilities are fully equipped for emergencies; all necessary systems and equipment are in

place and regularly tested; and all people know how to use equipment and communicate

during emergencies.

Ergonomics experts are provided when needed and are involved in patient safety assessment

and training.
454

All supervisors/managers assist in patient safety workplace analyses, ensure physical

protections, reinforce training, enforce discipline, and can explain how to provide safe

patient care.
455

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28. Krause TR, Seymour KJ, Sloat KCM. Long-term evaluation of a behavior-based method

for improving safety performance: a meta-analysis of 73 interrupted time-series

replications. Safety Science. 1999; 32: 1-18.

29. Helmreich RL, Merritt AC. Culture at work in aviation and medicine : national,

organizational, and professional influences. Aldershot ; Brookfield, VT, USA :: Ashgate;

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30. Peters TJ, Waterman RH. In search of excellence : lessons from America's best-run

companies. New York :: Harper & Row; 1982.

31. Deal TE, Kennedy AA. Corporate cultures : the rites and rituals of corporate life.

Reading, Mass. :: Addison-Wesley Pub. Co.; 1982.

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33. Baskin, Susan T (Osborn) and Shortell SM. Total Quality Management: needed research on

the structural and cultural dimensions of quality improvement in health care organizations.

The Journal of Health Administration Education. 1995; 13:143-154.

34. Helmreich RL, Foushee HC, Benson R, Russini W. Cockpit resource management:

exploring the attitude-performance linkage. Aviat Space Environ Med. 1986; 57: 1198-200.

35. Cooper MD. Towards a model of safety culture. Safety Science. 2000; 36: 111-36.

36. Geller ES. Ten Leadership qualities for a total safety culture. Professional Safety. 2000; 45:

30-32.

37. Spath P. Patient safety improvement guidebook. Forest Grove, OR: Brown-Spath &

Associates; 2000.

38. Shortell SM, Jones RH, Rademaker AW, Gillies RR, Dranove DS, Hughes EF, et al.

Assessing the impact of total quality management and organizational culture on multiple

outcomes of care for coronary artery bypass graft surgery patients. Med Care. 2000; 38:

207-17.

39. Klein RL, Bigley GA, Roberts KH. Organizational culture in high reliability organizations:

An extension. Human Relations. 1995; 48: 771-93.

40. Billings CE, Reynard WD. Human factors in aircraft incidents: results of a 7-year study.

Aviat Space Environ Med. 1984; 55: 960-5.

41. Billings CE. Some hopes and concerns regarding medical event-reporting systems: lessons

from the NASA Aviation Safety Reporting System. Arch Pathol Lab Med. 1998; 122: 214-

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42. Helmreich RL. On error management: lessons from aviation. BMJ. 2000; 320: 781-85.

43. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical

near miss reporting systems. BMJ. 2000; 320: 759-63.

44. Umiker W. Organizational culture: the role of management and supervisors. Health Care

Superv. 1999; 17: 22-7.

45. Glavin MPV, Chilingerian JA. Hospital care production and medical errors: organizational

responses to improve care. Current Top Management. 1998; 3: 193-215.

46. Manasee H, Jr. Close to home. Your own staff can solve many problems with your

hospital's medication system. Hosp Health Netw. 2001; 75: 82.

47. Findlay SE National Coalition on Health Care and the Institute for Healthcare

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http://www.ihi.org/resources/act/medical_errors.pdf. Accessed June 26, 2001.

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System. Washington, DC: Committee on Quality of Health Care in America, Institute of

Medicine. National Academy Press; 2000.
458

Section G. Systems Issues and Human Factors

Chapter 41. Human Factors and Medical Devices

Subchapter 41.1. The Use of Human Factors in Reducing Device-related

Medical Errors

Subchapter 41.2. Refining the Performance of Medical Device Alarms

Subchapter 41.3. Equipment Checklists in Anesthesia

Chapter 42. Information Transfer

Subchapter 42.1. Information Transfer Between Inpatient and Outpatient

Pharmacies

Subchapter 42.2. Sign-Out Systems for Cross-Coverage

Subchapter 42.3. Discharge Summaries and Follow-up

Subchapter 42.4. Notifying Patients of Abnormal Results

Chapter 43. Prevention of Misidentifications

Subchapter 43.1. Bar Coding

Subchapter 43.2. Strategies to Avoid Wrong-Site Surgery

Chapter 44. Crew Resource Management and its Applications in Medicine

Chapter 45. Simulator-Based Training and Patient Safety

Chapter 46. Fatigue, Sleepiness, and Medical Errors

Chapter 47. Safety During Transportation of Critically Ill Patients

Subchapter 47.1. Interhospital Transport

Subchapter 47.2. Intrahospital Transport
459

Chapter 41. Human Factors and Medical Devices

Harvey J. Murff, MD

Harvard Medical School

John W. Gosbee, MD, MS

Deparment of Veterans Affairs National Center for Patient Safety

David W. Bates, MD, MSc

Harvard Medical School

Introduction

Human factors engineering (HFE), also known as usability engineering or ergonomics, is

the study of how humans interact with machines and complex systems.1

 Through the merging of

cognitive psychology, engineering and other disciplines, human factors researchers have detailed

numerous principles concerning device and software program designs that allow for optimal

usage.2

 When these principles are violated, improper use of a machine is more likely to result.3,4

Specific examples have been detailed during observations of user errors with electronic infusion

devices.5

Medical device misuse is an important cause of medical error,6,7 and therefore,

incorporating human factors methodology into the design of medical devices has assumed an

important role in ensuring patient safety.2,8 This chapter first describes the use of HFE principles

as a safety practice in the design of medical devices and their evaluation both prior to and after

institutional purchase. Next, medical device alarms and the contribution of HFE to alarm

improvements will be evaluated. Finally, the chapter reviews the use of preoperative checklist

procedures to reduce anesthesia device failures (see also Chapter 23).

Subchapter 41.1. The Use of Human Factors in Reducing Device-related Medical Errors

Background

Human factors engineering is a powerful component in the design of usable, safe medical

devices.8

 HFE principles can be incorporated as safety practices that occur at various points

during device development and usage. Industry can use HFE principles at multiple times in the

design and developmental cycle of medical devices and software packages.3

 Health care

institutions can consider results of HFE evaluations when deciding which products to purchase.

Finally, HFE principles can also be incorporated into the ongoing evaluation of devices that have

already been purchased and are in use. While these practices have high face validity, there has

been little formal study of their effectiveness in reducing medical error. They are presented here

because they may hold promise if scrutinized rigorously, and to familiarize readers with their

potential to reduce medical error.

Design and Developmental Phase

Data collected by the United States Food and Drug Administration (FDA) in the late

1980s demonstrated that almost half of all medical device recalls resulted from design flaws.9

 In

1990, Congress passed the Safe Medical Devices Act, giving the FDA the ability to mandate

good manufacturing practices (GMP). These GMP involve design controls for manufacturers

that help ensure the use of HFE within medical device design.9

 As described in the Good
460

Manufacturing Practice Regulation, Design Control subsection (Title 21-Section 820.30), these

include the use of iterative design and testing during the developmental phase. The Act requires

that designs be “appropriate and address the intended use of the device, including the needs of

the user and patient.”

10 Multiple human factors techniques, such as user studies, prototype tests,

and task/function analysis, are utilized in the development and design process.

Manufacturers are required not only to use human factors principles to repeatedly test the

product in all phases of design, but also to validate the ultimate device design. Validation entails

testing the device, either in an actual clinical situation or a simulation, and documenting that the

device conforms to the individual user’s needs. Thus, manufacturers are required to apply HFE

methods through the multiple phases of device design and development cycles.10

Human factors engineering practices for medical device design and evaluation have been

well described. In 1993 the Association for the Advancement of Medical Instrumentation and the

American National Standards Institute established guidelines for the incorporation of HFE

principles into medical device design.11 This comprehensive document helped direct attention to

the problem of poor medical device design and helped establish the design standards necessary

to ensure safe medical equipment and thus should stand as the safety benchmark for industry.

Only limited data are available concerning the application of HFE principles to medical

device design, and most are not published. Nonetheless, the application of human factors

principles during a device’s design phase has been demonstrated to reduce user error. Patient

controlled analgesia (PCA) pumps are a case in point of how HFE principles in product design

reduce user error. User errors associated with poor interface design have been described with

PCA pumps.12,13 Lin and colleagues investigated whether applying human factors engineering

principles to the design of the user interface of a PCA pump could result in fewer dosage errors

as well as less time spent programming the device.14 Information on device usage was obtained

through cognitive task analysis. This involved observing and interviewing nurses operating PCA

pumps both in the laboratory setting and in the field. Utilizing this feedback, as well as other

human factors design principles, a “new” PCA pump interface was designed. Twelve recovery

room nurses were required to complete specific tasks with both the standard PCA user interface

and the newly designed interface. There were 29 programming errors on the traditional interface

and 13 on the redesigned interface (an error reduction of 55%, p<0.01). Furthermore, users were

able to program in the necessary orders in 18% less time.13

Another example involves the design of an ultrasound machine. In this study, Aucella

and colleagues15 interviewed sonographers, videotaped the ultrasound device being used, and

performed usability testing through simulation to collect information regarding the operatormachine interface of the ultrasound machine. After their extensive investigations they

implemented over 100 design changes to the console and control panel. Although errors with the

machine were not measured, comments collected by the authors from the beta operators of the

newly designed device suggested that the resulting machine was much easier to use.

There are enormous numbers of medical devices and software being designed and

developed. Thus the FDA has initiated several regulatory mechanisms to ensure compliance with

these guidelines. Some of the mechanisms include site inspections of manufacturers, review and

approval of medical devices before marketing, and review of medical device incident reports.16

Despite the tremendous amount of effort put forth by the FDA to ensure compliance with the

Good Manufacturing Practices Regulation, individual institutions should critically analyze

whether a device they intend to purchase meets HFE principles for user-centered design.
461

Device Evaluation Prior to Purchase

Adhering to HFE principles during initial design stages of a medical device is essential.

However, human factors analysis should also be incorporated into the institutional decision to

acquire a new medical device or software program.3

 Device purchasers should strongly consider

institution-specific human factors testing. Usability testing at the institutional level establishes

built-in redundancies to capture any design problems missed by manufacturers. Furthermore, the

users and environments at individual institutions will differ, possibly in important ways, from the

users and environments in which the device or program was initially designed and tested. It is

important for an institution to be aware of who the intended users of the device or software will

be, as well as where and when they plan to use the device. The information for such evaluations

may be obtained from vendors, from an in-house analysis, or from independent organizations.

Vendors must be able to prove to the FDA that the user will be able to operate the

medical device in the way in which it was intended.10 As companies are required to collect

human factors analysis data, it is important that institutions wishing to purchase a new medical

device or software receive and carefully review this information. Gosbee provides a list of

questions to ask a vendor before a purchase, which include: “How long does it take to learn to

operate the system? How long does it take to complete typical set-up tasks? What are the types

and frequency of errors that could happen, and the systems to thwart them?”

3

It is also important to consider the environment in which a device will be used.

Idiosyncratic features of the environment, such as excessive noise or poor lighting, and

differences in user skill or acuity due to fatigue or otherwise, may affect safety and the device’s

in-house usability.

Some institutions have developed in-house usability labs, in order to rigorously test any

device before purchasing. The Mayo Clinic uses simulations to test the usability of medical

software before purchasing.17 By carefully measuring user performance with the software they

are able to uncover latent errors in the design. The usability lab is also able to measure the time

necessary to learn to use the new software. This important information can help predict the

device’s or software’s influence on workflow as well as its predilection for operator misuse.

Even without sophisticated usability laboratories, an institution can use basic human

factors techniques to evaluate a product before purchase.3

 Powerful techniques such as cognitive

walk-through can be easily utilized at any institution. This involves observing the end-users of a

product interact with the product. As they attempt to use the device, they are instructed to “think

out loud.” Careful observation of the user’s actions and comments can identify potential design

flaws that might make it difficult to utilize the device or software.

Independent organizations are another potential source of information on device safety.

Unfortunately, most independent sources do not make clear to what degree HFE principles were

used in product evaluations, although they do provide some assessment of safety. One such

organization is ECRI (formerly the Emergency Care Research Institute), a nonprofit international

health services research agency. Another is the Institute of Safe Medical Practices (ISMP). Both

release newsletters and publications regarding product safety. By searching these and similar

databases, institutions can gather additional information concerning product safety prior to

purchasing a device. ERCI also publishes articles specifically geared to the institutions that

might wish to purchase a medical device or software.

Regardless of the level of pre-procurement testing, some unsafe designs will not be

detected until after the product is in use.3

 Therefore, it is important for institutions to

continuously evaluate these products to ensure safety.
462

Ongoing Device Evaluation

Devices and software at greatest risk for user error should be systematically evaluated.

This is particularly important in areas where multiple devices are used with different interfaces,

such as the operating room or the intensive care units.3

 Furthermore, areas where multiple

medications are stored together should be scrutinized for potential latent errors within device or

software user interfaces prior to user errors occurring.

Resources are available that can help direct an institution’s search. Through publications

from the FDA, ECRI, ISMP and similar organizations, medical device problems identified at

other institutions can be targeted. Thus an important safety practice may be using this published

information to search for latent errors within already purchased medical devices and applying

this information toward a directed product evaluation at the local institution.

Another potential safety practice is to educate practitioners about HFE principles to

increase awareness of medical device user error.3

 Several groups, including the American

Nurses’ Credentialing Center and the American Society of Health-Systems Pharmacists,

recommend incorporating HFE training within health care curricula as a means to reduce error.18

To create a culture of safety within medicine, practitioners must couple the ability to

identify potential design weaknesses with a change in the prevailing culture of silence

surrounding medical errors. Educational programs directed at health care providers in training

should address both of these important concerns. Curricula for teaching medical student and

medical residents HFE principles have been described18 and will likely be adopted at other

institutions. Casarett and Helms caution that an unintended result of error curriculum19 may be

that residents become too willing to attribute an error to system causes. Their concern is that the

resident will ignore any possible individual contribution to the adverse medical event and not

learn from analyses of the event. This concern has been discounted by Gosbee, stating that any

error-in-medicine curriculum should aim to “teach residents to see when errors are due to

inadequate skills and knowledge versus when they are due to inherent cognitive limitations and

biases.”

18

Subchapter 41.2. Refining the Performance of Medical Device Alarms

Background

Numerous aspects of patient care compete for providers’ attention and can reduce their

vigilance in monitoring medical devices. Alarms can alert providers to urgent situations that

might have been missed due to other distractions and have become a necessary part of patient

monitoring. In a study looking at critical incidents within a neonatal intensive care unit, 10%

were detected through alarms.20

However, fundamental flaws in the design of current alarm systems likely decrease their

impact.21 There are reports documenting some alarm failings in the medical literature,22 but few

data address interventions to improve alarm system effectiveness. For an alarm to be effective it

requires that a medical problem trigger the alarm, that personnel identify the source and reason

for the alarm, and that the medical problem be corrected prior to patient injury. This section

reviews 2 aspects of alarm safety: (1) the use of HFE principles in the redesign of medical alarms

to improve identification of the source and reason for alarm, and (2) practices in both device

design and programming that may improve safety by decreasing false positive alarms.
463

Identification of Alarm Source and Reason

The recognition accuracy of alarms within the operating room is quite low. When

presented with alarm sounds and asked to identify the source, anesthesiologists, operating room

technicians, and operating room nurses correctly identify the device producing the alarm only 33

to 53.8% of the time.23-25 Furthermore, experiments suggest that humans have difficulty reliably

recognizing more than 6 alarms at one time.26 The sheer number of different medical devices

with alarms can make it difficult to discern one alarm from another and studies within the human

factors literature have documented the inability of medical providers to discern between high

priority and low priority alarms.27 While this is a known problem in operating rooms and

intensive care units, how well alarms are recognized in other settings has not been described.

Some effort has been made to improve alarm systems through redesign.28 One nonmedical study examined ways to improve the recognition of auditory alarms by comparing

abstract alarm sounds with specially designed alarms using speech and auditory icons.29 Other

studies within the human factors literature have revealed certain acoustical properties that are

more likely to result in a higher sense of perceived urgency by the operator.

In a series of experiments, Edworthy required subjects to rank the level of urgency

associated with different alarms.30 The acoustical properties of the alarms were altered for the

different subjects. Level of urgency was then correlated with a specific alarm sound. After

ranking a set of acoustic parameters based on perceived urgency, the experimenters predicted

what urgency ranking the alarm would receive and played the alarms for a new set of subjects.

The correlation between the subjects’ urgency rating and the investigators’ predicted ratings was

93% (p<0.0001). Acoustical properties such as fundamental frequency, harmonic series, and

delayed harmonics all affected the users perceived urgency.

Another study looked at the redesign of an alarm to improve detectability within the

operating room.31 An alarm that was spectrally rich, frequency-modulated, and contained small

amounts of interpolated silence was detectable with at least 93% accuracy over background

operating room noise. However, both of these alarm experiments have only been done in

laboratory settings. In addition, Burt and colleagues found that when subjects were required to

urgently perform a task, the prior acoustically manipulated perception of urgency was ignored in

order to attend to the situational urgency of the task.32 Furthermore, with both alarms and clinical

tasks competing for an operator’s attention, the newly designed alarm might not be as

discernible. It has continued to be a challenge to create the best auditory alarm sound to indicate

an emergency.

Visual Interfaces for Alarms

Alarms can also be visual. Some research has been done to improve hemodynamic

monitoring device displays. Responses to abnormal values are delayed when workload for the

anesthesiologist is high,33 prompting interest in improving current visual displays. Furthermore,

the clinical decision process often rests on the practitioner’s interpretation of a patient’s

hemodynamic parameters. Thus, it is important that this information be presented in a way that

assists with decision making and minimizes errors of interpretation.

Two observational studies have compared different visual displays of data to traditional

visual monitors.34,35 Each evaluated errors in performing a designated task as well as response

time to completion. One measured how quickly subjects recognized a change in a parameter34

and the other measured how long it took for anesthesiologist to manipulate a set of abnormal

parameters to a stable set.34,35 Both studies used computerized simulations of anesthesiology
464

cases, with subjects serving as their own controls. In one study, subjects were required to

identify when changes in physiologic parameters occurred using different visual formats.34

Response time and accuracy to the simulated cases was compared among a histogram, polygon,

and numerical display. Subject responses were more accurate with the histogram and polygon

displays (p=0.01).

In the other study, 20 anesthesiologists with an average working experience of 5 years

were required to perform specific tasks on an anesthesia simulator35 (see Chapter 45). The tasks

consisted of returning a set of abnormal hemodynamic parameters to normal using intravenous

medications. A specific time for the completion was determined and this time was compared

among 3 different visual interfaces. Trial time was significantly shorter with the traditional

display (p<0.01), yet there were fewer failed trials using the other monitor displays (26% with

the profilogram display, 11% with the ecological display, and 42% with the traditional display).

The slower time with the non-traditional displays could have resulted from the subject’s lack of

experience with such screens. Nevertheless, the newer interfaces produced fewer failed attempts

at arriving at the appropriate hemodynamic parameters on the simulator, suggesting that these

displays might improve the clinical decision process.

None of the studies comparing traditional auditory alarms and visual monitor displays

reported any adverse event associated with the newer technology. However these studies are

limited by the artificial nature of the experiments.29,34,35 Anesthesiologists have many tasks to

perform during anesthesia, often amidst great distraction. Attending to monitors is only one

aspect of their workload. Because these laboratory experiments do not include all of the different

“real world” problems and diversions that an anesthesiologist might face, it is difficult to

generalize them to the workplace. Also, because this experimental task might be taken out of the

context of caring for a patient in the operating room, the subject might simply focus on the

completion of the experimental task and not consider other tasks that the anesthesiologist would

be required to perform in a real situation.
465

Decreasing the Frequency of Alarms

Poorly designed device alarms can create not only problems with alarm recognition but

also frequent false positive alarms. Two observational studies found that from 72 to 75% of

alarms during routine general anesthesia did not require corrective action.36,37 Another study

showed that only 3% of all auditory alarms during routine anesthesia monitoring represented a

patient risk.38 Providers frequently must interrupt clinical tasks to silence these false positive

alarms. More concerning is the fact that when alarms are unreliable, they tend to be ignored.21,39

This “cry-wolf” effect is a significant detriment to the optimal performance of alarm systems and

may result in dire consequences when “true alarms” are ignored.

False alarms can be managed in two ways. Devices can be designed so that they identify

and eliminate false alarms before triggering or users can manipulate alarm parameters to reduce

false alarms. User manipulation can range from adjusting alarm thresholds40 to even turning the

alarms off.22 There are no data describing how often operators reset alarm parameters to reduce

false positive rates.

Some research has focused on the identification of alarm parameters that improve or

optimize alarm accuracy (ie, to improve the ratio of true positives to false positives—the “signalto-noise” ratio). For example, Rheineck-Leyssius and Kalkman studied how altering an alarm

parameter on a pulse oximeter would affect the incidence of hypoxemia.40 Consecutive patients

admitted to the recovery room of a regional hospital in the Netherlands after general or regional

anesthesia were randomized to either a lower limit of SpO2 90% or SpO2 85%. The 2 groups

were comparable at baseline. The outcomes measured were hypoxemia, defined by a pulse

oximeter reading less than or equal to 90% or 85%. The authors were also required to judge if

they believed a signal to be artifact versus a true positive. The authors were blinded as to which

group the subject was randomized to during artifact assessment and data analysis. The relative

risk of having a hypoxic episode (Sp02≤85%) in the group with the lower alarm limit set at 85%

(as compared with those with the lower alarm limit set at 90%) was 3.10 (95% CI: 1.32-7.28,

p<0.001). One weakness of this study was the lack of a bedside observer to verify the validity of

the measurement, so that it is unclear to what degree measurement bias could have affected the

results. The pulse oximeter was considered the “gold standard” for measuring hypoxia and thus

false positives were calculated based on alarm artifact rates (outliers, loss of signal). Keeping the

lower alarm limit for a pulse oximeter at 90% did reduce the number of patients with hypoxemia,

however it also increased the false positive rate (33% versus 28%). A higher false positive rate

on an alarm could make it more likely that an operator might disregard the alarm. The majority

of alarms were transient and lasting less than 20 seconds. The authors also noted a 60%

reduction in the number of triggered alarms in the Sp02 90% group by introducing a “theoretical

delay” of 15 seconds between crossing the alarm threshold and actually triggering the alarm.

Other investigators have documented a 26% reduction in mean alarm rate by increasing the

alarm delay from 5 to 10 seconds.41

Overall, only modest evidence supports the practice of not lowering pulse oximeter lower

alarms limit settings below 90%. This intervention could reduce hypoxemic events with little

added cost. However, there would be an increased number of false positive alarms, which might

affect attendance to the device. Fortunately, newer technological advances in oximetry appear to

reduce false positives rates and may make this less of a problem. In a study in the Netherlands, a

conventional pulse oximeter was compared with a “third generation” pulse oximeter equipped

with a signal processing technique designed to reduce false positives.42 This “smart” pulse

oximeter applied signal quality tests, differentially amplified the input signal, and applied
466

motion-detection testing to the identified pulse. The “smart” pulse-oximeter only triggered one

false positive (an alarm that did not coincide with hypoxia) and had a relative risk of 0.09 (95%

CI: 0.02-0.48) for generating a false positive alarm when compared with conventional pulse

oximetry with a 21-second delay.

Comment

Observational studies have suggested that current alarm systems could be improved, but

future laboratory studies are needed to determine which properties of alarm systems are most

effective to alert operators. These tests must be followed by field studies and ultimately with

trials looking at actual patient outcomes to determine the best designs. Information concerning

the cost and feasibility of implementing these changes should also be gathered.

False positive alarms remain a significant problem. Few data exist on the incidence of

resetting alarm parameters or at what parameter values alarm accuracy is optimized. Advances in

alarm technology aimed at reducing false positives appear a promising alternative to resetting

parameters.

Subchapter 41.3. Equipment Checklists in Anesthesia

Events related to medical equipment can be divided into two categories, user-error and

equipment failure.43 Health device inspection and preventive maintenance by biomedical or

clinical engineering departments have high face validity as an important patient safety practice in

reducing equipment failure.

There are many calls in the engineering literature to standardize equipment

maintenance.44-46,46 Standardization of protocols is believed to help make the processes more

efficient and reduce errors.47 However, it has been difficult to standardize equipment

maintenance practices due to a lack of the appropriate units on which to base measurement.46

Some authorities have suggested outcomes based on engineering endpoints such as reliability

and accuracy.48 Others have tried to validate a set of maintenance outcome units based on cost or

quality metrics.44,45,49 Some engineers have suggested the incorporation of clinical endpoints into

medical equipment assessment.48,50 Notwithstanding differing views as to measurement of

endpoints, experts uniformly believe that standardization of engineering endpoints is vital to

ensure adequately inspected and maintained equipment.46 No studies to date have developed a

widely used standardized protocol for equipment maintenance for clinical engineering

departments, largely because the lack of standardization of endpoints renders assessing the

relative value of any particular maintenance protocol impossible.44-46,48,50 Nonetheless,

equipment failure does result in a small fraction of clinical events and thus is an important safety

intervention. Hopefully, future studies will help delineate the most effective practices for

equipment maintenance processes.

Use of checklists is another practice that helps ensure equipment readiness, particularly

for equipment that is needed in critical situations and/or where equipment failure may have dire

consequences. For example, a nurse at the beginning of each shift may use a checklist to ensure

the readiness of a hospital ward’s resuscitation cart (“crash cart”) should it be needed (eg, the

defibrillator is plugged-in and charged, the back-up suction pump works, medication is not past

its expiration date). Similarly, a perfusion technologist can use a checklist to ensure cardiac

bypass circuit and back-up equipment are ready before surgery. Published studies on the

effectiveness of equipment checklists largely relate to the use of preoperative checklists to

prevent anesthesia equipment failures since, to date, studies on the effectiveness of equipment
467

checklists in medicine have been limited to this area.51-53,54 These studies are reviewed in

Chapter 23.

Final Comment to Chapter 41

Human factors testing is yielding important data regarding safe and effective medical

device and alarm designs that take into account the users’ cognitive limitations. Machines can be

designed and redesigned that enhance patient safety, rather than compromise it.

Currently, there are no widely accepted standards for equipment maintenance intervals

and protocols. Maintenance endpoints that incorporate clinical events as one component of the

endpoint have been suggested. Until a reliable and validated engineering endpoint metric is

widely recognized it will remain difficult to investigate the most effective maintenance practices.

Other than the pioneering work in anesthesiology, HFE has been underutilized in

medicine. Hopefully, in the near future, more attention will be focused on integrating human

factors engineering within all aspects of medical training and practice, which will help create a

culture of safety.

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design of medical equipment: patient- controlled analgesia. J Clin Monit Comput. 1998;

14(4):253-263.

15. Aucella A, Kirkham T, Barnhart S, Murphy L, LaConte K. Improving ultrasound systems

by user-centered design. In: Proceedings of the Human Factors and Ergonomics Society.

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16. Sawyer D. Medical device requirements, human factors, and the food and drug

administration. In: Proceedings of the Human Factors and Ergonomics Society 44th

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17. Claus P, Gibbons P, Kaihoi, BH, Mathiowetz M. Usability lab: A new tool for process

anaylsis at the Mayo Clinic. In: HIMSS Proceedings. Chicago: Healthcare Information

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18. Gosbee J. Human Factors Engineering is the Basis for a Practical Error-in-Medicine

Curriculum. First Workshop on Human Error in Clinical Systems.

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19. Casarett D, Helms C. Systems error versus physicians' errors: Finding the balance in

medical education. Acad Med. 1999; 74:19-22.

20. Frey B, Kehrer B, Losa M, Braun H, Berweger L, Micallef J et al. Comprehensive critical

incident monitoring in a neonatal-pediatric intensive care unit: experience with the system

approach. Intensive Care Med. 2000; 26(1):69-74.

21. Woods D. The Alarm Problem and Direct Attention in Dynamic Fault Management.

Ergonomics. 1995; 38(11):2371-2393.

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23. Finley GA, Cohen AJ. Perceived urgency and the anaesthetist: responses to common

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operating room and intensive care unit. Ergonomics. 1993; 36:1159-1176.

26. Patterson R, Milroy R. Auditory warnings on civil aircraft: the learning and retention of

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28. Edworthy J, Stanton N. A user-centred approach to the design and evaluation of auditory

warning signals: 1. Methodology. Ergonomics. 1995; 38:2262-2280.

29. Leung YK, Smith S, Parker S, Martin R. Learning and Retentiono of Auditory Warnings.

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warning sound parameters and perceived urgency. Hum Factors. 1991; 33:205-231.
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76:337-341.

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the 1997 survey. Biomed Instrum Technol. 1998; 32:136-144.

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from gas delivery equipment: a closed claims analysis. Anesthesiology. 1997; 87:741-748.
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54. March MG, Crowley JJ. An evaluation of anesthesiologists' present checkout methods and

the validity of the FDA checklist. Anesthesiology. 1991; 75:724-729.
471

Chapter 42. Information Transfer

Harvey J, Murff, MD

David W. Bates, MD, MSc

Harvard Medical School

Introduction

Patient safety can be compromised by discontinuities in care. Studies suggest that

discontinuity results from poor information transfer1

 and faulty communication,2 which in turn

may cause avoidable adverse events.3

Improving information transfer and communications among health care providers is an

important patient safety practice and has been strongly recommended as a means to improve

patient care.1,3-7 This chapter evaluates safety practices involving improvements of provider-toprovider information transfer. Practices for evaluation include transfer of information between

inpatient and outpatient pharmacies (Subchapter 42.1), sign-out systems for medical housestaff

(Subchapter 42.2), automatically generated electronic discharge summaries (Subchapter 42.3),

and systems to improve patient notification of abnormal results (Subchapter 42.4).

Subchapter 42.1. Information Transfer Between Inpatient and Outpatient Pharmacies

Background

Accurate and timely information transfer between community and acute care pharmacies

is an important safety practice. Patients admitted to the hospital could benefit from the hospital’s

pharmacy obtaining better information concerning their medication allergies as well as prior

therapeutic failures.8

 Furthermore, when patients transition from acute care to outpatient care,

changes in medications that occurred during hospitalization may cause confusion for both

patients and providers. In one study surveying patients one week after hospital discharge,

patients’ knowledge of their drug indications were worse for medications introduced during their

hospitalization than for those taken prior to hospitalization (OR 0.69, 95% CI: 0.53-0.89).9

Confusion and incomplete information may increase the risk of under- or

overmedication, harmful drug interactions, and other problems. Existing literature suggests that

pharmacist interventions may reduce potential adverse drug events and have a modest impact on

patient morbidity and mortality.10,11 However, these studies have used independent reviewers to

judge the impact of the intervention and have not specifically measured adverse drug events or

patient outcomes. Clinical pharmacists’ consultations prior to discharge might also improve

patient medication compliance (see Chapter 7).12

Uncontrolled studies report that information-exchange programs between hospital and

community pharmacies are perceived as beneficial and may have a positive impact on patient

outcomes.13 Although not the primary outcome measured in their small (n=127) observational

study, Dvorak et al did note that using a pharmacy-to-pharmacy referral form was effective in

preventing 2 medication errors. Thus, practices that improve information transfer between

hospital and community pharmacies may improve patient safety.

Of the many potential methods for improving information transfer between hospitals and

outpatient pharmacies, controlled trials have been reported in the literature for only 2:

pharmaceutical care plans cards14 and patient information facsimiles between pharmacies.8

Although direct electronic communication of pharmacy data may be superior to these methods,
472

no controlled studies are currently available regarding this practice and therefore it is not

reviewed within this chapter.

Practice Description

In a study by Smith and colleagues, patients received a card prior to discharge listing

their pharmaceutical care plan, which included medication doses, indications, schedules, side

effects, information as to the importance of drug compliance, and how to obtain medication

refills.14 Patients were instructed to give the card to their community pharmacist. In another

study, the intervention consisted of pharmacy-to-pharmacy facsimile transmission at the time of

admission and discharge from the hospital.8

 In this study, when a patient was admitted to the

hospital their community pharmacy transmitted patient demographic information, historical

information concerning allergies and adverse drug reactions, current medications, refill history,

pharmacist’s monitoring notes, communications with patient and physician, and a detailed

medication history to the admitting hospital. After discharge the hospital pharmacy transmitted

to the community pharmacy a list of any potential medication problems identified by the hospital

pharmacist on admission, the patient’s daily monitoring log, the pharmacist’s discharge

summary, and a discharge medication table. The medical records department of the hospital also

transmitted the patient’s discharge summary and laboratory test results to the community

pharmacy.

Prevalence and Severity of the Target Safety Problem

Medication problems can arise because patients are frequently discharged from the acute

care hospital on medications different from their ambulatory regimen.15 Elderly patients in

particular are at risk after discharge.16 In one study, hospital providers changed 53% of the drugs

prescribed by the primary care providers.15

The extent to which these medication changes and lack of communication result in

recently discharged patients failing to receive medications or appropriate monitoring for their

drug therapy is unclear. In one study of elderly patients, 32% of medications prescribed at

discharge were not being taken 2 days after discharge.17 Another study found that 51% of

patients recently discharged from acute care hospitals had deviated from their prescribed

regimen.18 Of those that had deviated from the prescribed drug regimen, 70% did not understand

the medication regimen. In a Scottish study, recently discharged, elderly patients were issued a

5-day supply of their medication on discharge and visited in their homes after these 5 days had

elapsed.16 Twenty-seven percent of the patients had not received a new prescription ordered on

discharge. Of the patients with new prescriptions issued, 19% received inaccurately labeled

medications. Medications were considered mis-labeled when non-specific container labels, such

as “take as directed” replaced the more specific labels given on discharge. Some authors have

suggested that improving communication about medications prior to and just after hospital

discharge might reduce these medication errors.18,19

Poor communication is not the only problem.16 Patient factors influence whether a

medication is ultimately picked up and taken as directed. Deviations from prescribed drug

regimens are multifactorial and improving pharmacy-to-pharmacy communication is only one

aspect of the overall problem.

Opportunities for Impact

Data from primary care providers reveal that 96% of the respondents would like

information concerning hospital drug changes.20 Ninety-four percent of community pharmacists
473

surveyed also wished to be provided with information concerning hospital drug changes.20 We

were unable to identify data regarding what percentage of hospital pharmacies routinely transfer

information on patients’ medication regimens when they are admitted to and discharged from

acute care.

Study Design and Outcomes

Two controlled studies were identified in the literature (Table 42.1.1). Both were

randomized trials but neither was blinded. In Smith et al, patients received a written pharmacy

care plan at discharge. Home visits were made 7 to 10 days later to assess compliance and

discrepancies in the medication that patients were taking versus those ordered at discharge

(Level 2).14 In the study by Kuehl et al,8

 patients were randomly assigned to either usual care or

to a bi-directional exchange of pharmacy information by facsimile between the ambulatory

pharmacy and the admitting hospital, upon admission and discharge (Level 1). The outcomes

were pharmacist interventions, such as changing medication doses or making allergy

recommendations (Level 2).8

Evidence for Effectiveness of the Practice

Smith et al’s small study (n=53) of a pharmacy care plan card found that in both groups

patients were taking different medications than those ordered at discharge. The authors found

that compliance with post-discharge medications was significantly better in the group that had

received the information card (p<0.01). Unintentional changes to the medication were found in

14/28 (50%) of the study patients and 17/25 (68%) of the control patients during the follow-up

visits (Pearson’s chi-square p=0.18)

In the study by Kuehl et al, significantly more experimental group patients than control

group patients had at least one in-hospital pharmacist intervention documented (47% vs. 14%,

p<0.001). The mean number of in-hospital pharmacist interventions per patient was also

significantly higher in the experimental group (1.0 vs. 0.2, p<0.0001). The types of interventions

made by hospital pharmacists included addition of a medication the patient was taking as an

outpatient that was not originally ordered on admission, dosage changes, and changes related to

drug allergy. Interventions by ambulatory care pharmacists were also more frequent in

experimental group patients compared with control group patients. Community pharmacists who

received hospital pharmacy records performed interventions on one or more patients 42% of the

time, while no interventions were performed in the control group (p=0.001). Specific community

pharmacist interventions included monitoring of therapy (13/57), taking actions related to drug

allergy problems (13/57), requesting documentation of an indication for a particular medication

(9/57), and making a dosage change (8/57).

Although the data abstractor was blinded with regard to study group, the nature of the

intervention did not permit blinding of participating pharmacists (ie, they received faxed

information for some patients but not others). Also, the pharmacists were not explicitly blinded

to the study’s objectives. It is unclear how this knowledge might have affected the results. It

could have resulted in more careful scrutiny of any potential drug problem (bias away from the

null) or less scrutiny of these orders (bias towards the null). Kuehl et al note that although the

results suggest discriminatory documentation did not play a major role, the possibility cannot be

ruled out.

Another potential limitation of this study was the completeness of follow-up. Of the

eligible patients from ambulatory care pharmacies, only 50% returned to their pharmacy during

the study period. There were no comparisons presented between the ambulatory pharmacy visit
474

group and the loss to follow-up group. This large loss to follow-up could have significantly

altered their findings.

Potential for Harm

None of the studies evaluating different hospital-community pharmacy communication

processes detailed any adverse events. However, the degree of added workload and effects on

current workflow must be taken into account.

Costs and Implementation

The 2 reviewed interventions for improving hospital to community pharmacy information

transfer seemed simple and relatively inexpensive.8,8,13,14,14 Although no formal cost analysis was

performed, Dvorak et al described their method (use of a pharmacy-to-pharmacy referral form)

as being “labor-intensive.” No records were kept of the time necessary to provide the referrals

but the authors estimated the time commitment per patient to be 30 minutes.13 It is also important

to note that complete information transfers occurred for 75% of the subjects in Kuehl’s study,

indicating that there is still room for improving the process. With improvements in information

transfer technology, automated transfer of information from hospital to community pharmacy

could have important patient safety benefits without excessively increasing providers’

workloads.

Comment

Providing patients with data forms to convey transfer of information between hospital

and ambulatory pharmacies has potential for reducing discontinuities resulting from inadequate

medication information. Few studies have evaluated the effect of these interventions on patient

outcomes, although any improvement in the transfer of this information would likely be well

received by ambulatory providers. Future studies are necessary to determine if and how

improved pharmacy-to-pharmacy communications reduce preventable adverse drug events and

improve patient outcomes. Identifying the most effective and least disruptive forms of interpharmacy communication remains an area for further investigation.
475

Table 42.1.1. Practices to improve transfer of medication information

Study Study Setting Intervention Study Design,

Outcomes

Results

Smith,

199714

53 patients (>65 yrs

old) discharged to

home who were

likely to experience

difficulties with their

medications

Copies of medication

doses, indications, side

effects, importance of

compliance and refill

information given to

patients at discharge

Level 1,

Level 2

Patients taking medication

not prescribed at discharge:

information card 75%, control

96% (p<0.01)

Kuehl,

19988

156 patients

admitted to small

mid-western

community hospital

Pharmacy-to-pharmacy

facsimile transmission o

medication regimen at

time of admission and

discharge from hospital

Level 1,

Level 2

Patients with • 1 pharmacist

interventions in hospital: faxedsummary 47%, control 14%

(p<0.001)

Patients with • 1 pharmacist

interventions in community:

faxed summary 42%, control

0% (p<0.05)

References

1. Cook RI, Render M, Woods DD. Gaps in the continuity of care and progress on patient

safety. BMJ. 2000; 320:791-794.

2. Donchin Y, Gopher D, Olin M, Badihi Y, Biesky M, Sprung CL et al. A look into the

nature and causes of human errors in the intensive care unit. Crit Care Med. 1995; 23:294-

300.

3. Gosbee J. Communication among health professionals. BMJ. 1998; 316:642.

4. Sentinel events: approaches to error reduction and prevention. Jt Comm J Qual Improv.

1998; 24:175-186.

5. Leape LL. Error in medicine. JAMA. 1994; 272:1851-1857.

6. Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan T et al. Systems

analysis of adverse drug events. ADE Prevention Study Group. JAMA. 1995; 274:35-43.

7. Nolan TW. System changes to improve patient safety. BMJ. 2000; 320:771-773.

8. Kuehl AK, Chrischilles EA, Sorofman BA. System for exchanging information among

pharmacists in different practice environments. Am J Health Syst Pharm. 1998; 55:1017-

1024.

9. Kossovsky MP, Micheli P, Louis Simonet M, Sarasin FP, Chopard P, Perneger TV et al.

Patients knowledge about their medication is disturbed by changes made during a hospital

stay. J Gen Intern Med. 2001; 16: 148.

10. Cameron B. The impact of pharmacy discharge planning on continuity of care. Can J Hosp

Pharm. 1994; 47:101-109.

11. Rupp MT. Value of community pharmacists' intervention to correct prescribing errors. Ann

Pharmacother. 1992; 26:1580-1584.

12. Lipton HL, Bird JA. The impact of clinical pharmacists' consultations on geriatric patients'

compliance and medical care use: a randomized controlled trial. Gerontologist. 1994;

34:307-315.
476

13. Dvorak SR, McCoy RA, Voss GD. Continuity of care from acute to ambulatory care

setting. Am J Health Syst Pharm. 1998; 55:2500-2504.

14. Smith L, McGowan L, Moss-Barclay C, Wheater J, Knass D, Chrystyn H. An investigation

of hospital generated pharmaceutical care when patients are discharged home from

hospital. Br J Clin Pharmacol. 1997; 44:163-165.

15. Himmel W, Tabache M, Kochen MM. What happens to long-term medication when

general practice patients are referred to hospital? Eur J Clin Pharmacol. 1996; 50:253-257.

16. Burns JM, Sneddon I, Lovell M, McLean A, Martin BJ. Elderly patients and their

medication: a post-discharge follow-up study. Age Ageing. 1992; 21:178-181.

17. Beers M, Sliwkowski J, Brooks J. Compliance with medication orders among elderly after

hospital discharge. Hosp Formul. 1992; 27:720-724.

18. Parkin D, Henney C, Quirk J, Crooks J. Deviations from prescribed drug treatment after

discharge from the hospital. BMJ. 1976; 2:686-688.

19. Katz E, Nicod P, Brunner HR, Waeber B. Changes in treatment during and after

hospitalization in patients taking drugs for cardiovascular disease. Cardiovascular Drugs

and Therapy. 1996; 10:189-192.

20. Munday A, Kelly B, Forrester JW, Timoney A, McGovern E. Do general practitioners and

community pharmacists want information on the reasons for drug therapy changes

implemented by secondary care? Br J Gen Pract. 1997; 47:563-566.

Subchapter 42.2. Sign-Out Systems for Cross-Coverage

Background

As physicians go off duty, they provide information to a “cross-covering” physician who

will care for patients in the interim. The process of information transfer, known as “sign-out,” is

often informal and unstructured. Various methods are used, including handwritten lists, PCbased word processing or spreadsheet programs, and personal digital assistants (PDAs), but little

literature has assessed their effectiveness in assuring continuity of care for patients and

preventing medical errors. Although notes in the medical record often contain all the information

needed to care for patients, cross-covering physicians make many decisions without the benefit

of the patients’ charts.1

 Jelley found lack of consistency in the content of weekend sign-out lists

in a community-based internal medicine inpatient program.1

 Lee and colleagues found that

medical interns recorded information elements such as patient age, DNR status, and medications

more often when a standardized sign-out card was used.2

 In this section, we review evidence of a

computerized sign-out system to reduce medical errors during cross-coverage.

Practice Description

The proposed safety practice is a structured sign-out process in which patient information

is provided for various standardized data fields. The computerized sign-out program described

by Peterson and colleagues consisted of a summary of the patient’s medical status, a problem

list, recent laboratory data, resuscitation status, allergies, and a “to do” list.3

 This information

was accessible from any computer within the hospital and was accessed and maintained on a

daily basis by housestaff physicians.

Prevalence and Severity of the Target Safety Problem

Discontinuities in provider care during hospitalization have been associated with an

increased risk of adverse events. The Petersen et al study found the odds ratio for a preventable
477

adverse medical event occurring during cross-coverage as opposed to regular provider coverage

to be 6.1 (95% CI: 1.4-26.7).4

 In the surgical domain, the Joint Commission on Accreditation of

Healthcare Organizations (JCAHO) publication on wrong-site surgeries noted a number of cases

involving last minute personnel changes.5

 It is possible that these rapid substitutions in the

operating room with inadequate communication may have contributed to these adverse events.

Opportunities for Impact

The number of hospitals using either a computerized or paper-based sign-out process is

unknown, but computerized sign-outs are probably unusual. One study found that 26% of

adverse events in a single institution occurred during cross-coverage.4

 These data suggest that a

standardized sign-out procedure could have a significant impact on improving patient safety.

Study Design and Outcomes

We identified one study evaluating the effect of a standardized sign-out system on the

occurrence of adverse events (Table 42.2.1). In this study, adverse medical events detected by

self-report were compared before and after implementation of a computerized sign-out system

(Level 3).3

 This study involved internal medicine housestaff and any management of a patient

performed by an intern from a different team or a night-float resident was considered crosscoverage. During chart review, the investigators recorded whether the physician at the time of

the event was the patient’s regular physician or a cross-covering physician. Adverse medical

events, defined as “an injury due to medical therapy that prolonged hospital stay or disability at

discharge”

3

 were the primary outcomes (Level 2).

Evidence for Effectiveness of the Practice

There were significantly fewer adverse events during the intervention period compared

with the baseline period (2.38% vs. 3.94%, p<0.0002). There was also a trend toward fewer

preventable adverse events with the intervention (1.23% vs. 1.72%, p<0.1) but no significant

difference in the rate of preventable events during cross-coverage (0.38% vs. 0.24%, p>0.10).

Using a logistic regression model including factors for Acute Physiology and Chronic Health

Evaluations (APACHE) II scores and alcohol use (the 2 variables significantly associated with

adverse events during the intervention period), the authors calculated the odds ratio for a patient

to experience an adverse medical event during cross-coverage in the baseline period to be 5.2

(95% CI: 1.5-18.2).

After implementation, the odds ratio for a cross-coverage adverse event was no longer

statistically significant (OR 1.5, 95% CI: 0.2-9.0).3

 The authors noted that housestaff used the

sign-out information not only for cross-coverage but for their primary patients as well, which

may have contributed to the overall decrease in adverse events. Secular trends may also have

played a role in this reduction.

Another limitation of this study was that it relied on self-report to capture adverse

medical events. The investigators performed a review of a random sample of 250 charts and

detected only 8 unreported, preventable adverse medical events. If extrapolated to the entire

sample (3747), this represents 120 missed adverse events. These adverse events could have

influenced the results either toward or away form the null hypothesis, depending on their

distribution among regular and cross-covering physicians.
478

Potential for Harm

The study reported no adverse events as a result of the sign-out system. As with other

sign-out systems, particularly those that are computerized or Web-enabled, the issues of data

security and protection of confidentiality must be addressed.6

Costs and Implementation

Implementation of a computerized sign-out system like that described by Peterson et al

would require information systems that allow extraction and aggregation of patient specific data

(eg, laboratory and pharmacy) and financial support for programming. These resources may not

be present at some institutions. Although housestaff responded favorably to the computerized

system, physicians at other institutions or in other specialties may not be as willing to use this

system.

Comment

One study has shown that an inpatient’s risk of preventable adverse events was less after

implementation of a computerized sign-out process. The method appears appropriately suited for

hospitals with cross-coverage arrangements similar to those described by Peterson et al,

specifically in-house coverage by resident trainees. It will be important to know if similar

systems are as effective and well received at other institutions, including those without trainees.

Such systems would be difficult to implement in hospitals with limited information systems or

where physicians outside the hospital provide coverage through paging systems. Although a

computerized system has the advantage of being accessible from any location in the hospital and

may be able to automatically import important information, events attributable to faulty

communication during cross-coverage could also be amenable to other strategies for

standardizing the process (eg, sign-out cards, Web-based programs, PDAs). No evidence is

available concerning the relative effectiveness of other standardized sign-out methods. Future

research should address what data fields are most helpful to physicians providing cross-coverage

in preventing adverse events and how different methods of standardized sign-out compare in

effectiveness (eg, handwritten cards vs. PDAs).
479

Table 42.2.1. Computerized sign-out program

Study Setting Study Design,

Outcome

Results (95% Confidence Intervals)

8767 patients admitted to

the medical service of a

tertiary care teaching

hospital in Boston3

Level 3,

Level 2

Odds ratio (OR) of preventable adverse events

occurring during cross-coverage compared with

care under regular physician:

baseline, OR 5.2 (1.5-18.2)

with intervention, OR 1.5 (0.2-9.0)

References

1. Jelley MJ. Tools of continuity: the content of inpatient check-out lists. J Gen Intern Med.

1994;9:77.

2. Lee LH, Levine JA, Schultz HJ. Utility of a standardized sign-out card for new medical

interns. J Gen Intern Med. 1996;11:753-755.

3. Petersen LA, Orav EJ, Teich JM, O'Neil AC, Brennan TA. Using a computerized sign-out

program to improve continuity of inpatient care and prevent adverse events. Jt Comm J

Qual Improv. 1998;24:77-87.

4. Petersen LA, Brennan TA, O'Neil AC, Cook EF, Lee TH. Does housestaff discontinuity of

care increase the risk for preventable adverse events? Ann Intern Med. 1994;121:866-872.

5. The Joint Commission on Accreditation of Healthcare Organizations. Sentinel event alert.

Lessons learned: wrong site surgery. 1998. Available at:

http://www.jcaho.org/edu_pub/sealert/sea6.html. Accessed June 27, 2001.

6. Balsbaugh TA. The family physician and handheld computers: a beginner's guide. The

Internet Journal of Family Practice 1[2]. 2001.

Subchapter 42.3. Discharge Summaries and Follow-up

Background

Discharge summaries are important tools for communicating pertinent patient

information regarding hospitalizations to outpatient care providers. Yet their relatively

unstructured, narrative format often invites inaccuracies.1

 In addition, there can be significant

delays transmitting discharge summaries to patients’ health care providers.2,3

Prior studies have investigated processes to improve discharge summaries, such as

standardizing their format4-6 and instituting physician education programs.7

 This chapter focuses

on the use of structured, database-generated discharge summaries to improve the quality of the

information content communicated after patient discharge, as well as to reduce the time required

for this information transfer.8

Practice description

During the hospital course, physicians provide information corresponding to specific

sections of the computerized discharge summary either on data collection forms which are

manually entered into a database8

 or directly into a computer system. When the patient is

discharged the database generates a structured discharge summary that can be sent to the

patient’s outpatient providers.
480

Prevalence and Severity of the Target Safety Problem

In one study examining the effectiveness of inpatient follow-up care, 9.7% of discharged

patients experienced worsening of symptoms or functional capacity as a result of an inadequately

managed discharge process.2

 Hospital discharge summaries are an important means of

communication between hospital and community physicians, but have several problems. First,

community physicians do not always receive summaries for recently discharged patients. In one

study only 34% of patients had a discharge summary sent to their outpatient care provider.2

Although no analysis was undertaken to determine if receiving a discharge summary had an

effect on patients’ follow-up, another study demonstrated that patients may be less likely to be

readmitted to the hospital if their primary care provider receives a discharge summary.9

As mentioned above (Subchapter 42.1), patients frequently have their medication

regimen changed while admitted.10 The majority of ambulatory providers would like to have

information regarding these medication changes.11 Improvement in information transfer from

acute care to ambulatory care might reduce medication discrepancies; however, patient

compliance will also heavily influence these factors.

Opportunities for Impact

We found no data describing how many hospitals currently use database-driven discharge

summaries.

Study Design and Outcomes

Several studies were identified that evaluated electronically generated discharge

summaries, but these were limited by a lack of randomization or limited outcomes reporting.12-14

One randomized controlled trial was identified that compared traditional dictated discharge

summaries to summaries generated from a database (Table 42.3.1).8

 The primary outcome was

the proportion of admissions with a discharge summary completed by 4 weeks after discharge

(Level 3).8

 Overall quality of the discharge summaries was also assessed (Level 3) but patient

level outcomes were not.

Evidence for Effectiveness of the Practice

Patients randomized to the database group were significantly more likely to have a

discharge summary generated within 4 weeks of discharge than were patients randomized to the

dictation group (113/142 vs. 86/151, p<0.001). Even with the database method, 20% of patients

did not have a completed discharge summary by 4 weeks. Of the patients with a discharge

summary generated within 4 weeks of discharge, 94.7% of the database-generated summaries

were produced within one week, while only 80.2% of the dictated discharge summaries were

completed in this timeframe (p<0.001). Physician ratings of the quality and timeliness of the

discharge summaries were available for 210 of 302 (69.5%) summaries. The quality and

timeliness of the 2 summaries were judged to be similar overall, but differed when stratified by

provider specialty. Database-generated summaries were thought to be more timely by family

physicians (p=0.04) and of lower quality by consultant physicians (p=0.02).

Potential for Harm

No adverse events were mentioned as a result of the database-generated discharge

summary study.
481

Costs and Implementation

The direct and indirect costs of implementing and maintaining a system for databasegenerated discharge summaries have not been formally evaluated in the literature. Results of a

mail survey of housestaff in the van Walraven study8

 suggest their intervention did not adversely

affect the workflow of housestaff physicians. Housestaff significantly preferred (p<0.001) the

database system and found it less burdensome (p=0.002). With the advent of electronic medical

record systems, data can be automatically abstracted from various fields and collated into a

discharge summary, eliminating the costs associated with abstraction form distribution,

collection, and data entry. This is already a practice at some institutions.12,15

Comment

With the documented inefficiencies, inaccuracies and incompleteness of discharge

summary information, interventions that improve the hospital discharge communication process

without increasing provider workload could have a significant impact. A database method can

significantly decrease the time for completion of discharge summaries. The amount of work

required to generate the database discharge summaries could potentially be reduced in the future

through electronic record-keeping. Further studies are required to determine how to best transfer

discharge summary information to outpatient providers. A feasibility study has assessed the

utility of faxing discharge summaries to community providers.3

 This remains an active area for

study, recognizing that the optimal strategy to reduce discontinuities in care after hospital

discharge will depend on the methods for generating discharge summaries, the accuracy and

usefulness of their content, and the timeliness and method of their delivery to patients’ providers.

Table 42.3.1. Improvements in discharge summary communications

Study Study Setting Study Design,

Outcome

Results

van Walraven,

199933

293 patients admitted to the

General Medicine Service of

a tertiary care teaching

hospital in Ottawa

Level 1

Level 3

Discharge summary completed

within 4 weeks:

database group, 79.6%

dictation group, 57% (p<0.001)

References

1. Macaulay EM, Cooper GG, Engeset J, Naylor AR. Prospective audit of discharge summary

errors. Br J Surg 1996; 83:788-790.

2. Brook RH, Appel FA, Avery C, Orman M, Stevenson RL. Effectiveness of inpatient

follow-up care. N Engl J Med 1971; 285:1509-1514.

3. Paterson JM, Allega RL. Improving communication between hospital and community

physicians. Feasibility study of a handwritten, faxed hospital discharge summary.

Discharge Summary Study Group. Can Fam Physician 1999; 45:2893-2899.

4. King MH, Barber SG. Towards better discharge summaries: brevity and structure. West

Engl Med J 1991; 106:40-41, 55.

5. Lloyd BW, Barnett P. Use of problem lists in letters between hospital doctors and general

practitioners. BMJ 1993; 306:247.
482

6. Rawal J, Barnett P, Lloyd BW. Use of structured letters to improve communication

between hospital doctors and general practitioners. BMJ 1993; 307:1044.

7. Flyer B, Rubenstein LZ, Robbins AS, Wieland GD, Henry D, Cugalj N. An intervention to

improve the hospital discharge summary. J Med Educ 1988; 63:407-409.

8. van Walraven C, Laupacis A, Seth R, Wells G. Dictated versus database-generated

discharge summaries: a randomized clinical trial. CMAJ 1999; 160:319-326.

9. van Walraven C, Seth R, Austin P, Laupacis A. The effect of discharge summaries on

readmission to hospital. 2001. [unpublished work]

10. Himmel W, Tabache M, Kochen MM. What happens to long-term medication when

general practice patients are referred to hospital? Eur J Clin Pharmacol 1996; 50:253-257.

11. Munday A, Kelly B, Forrester JW, Timoney A, McGovern E. Do general practitioners and

community pharmacists want information on the reasons for drug therapy changes

implemented by secondary care? Br J Gen Pract 1997; 47:563-566.

12. Lissauer T, Paterson CM, Simons A, Beard RW. Evaluation of computer generated

neonatal discharge summaries. Arch Dis Child 1991; 66(4 (Spec No)):433-436.

13. Llewelyn DE, Ewins DL, Horn J, Evans TG, McGregor AM. Computerised updating of

clinical summaries: new opportunities for clinical practice and research? BMJ 1988;

297:1504-1506.

14. Smith RP, Holzman GB. The application of a computer data base system to the generation

of hospital discharge summaries. Obstet Gynecol 1989; 73(5 Pt 1):803-807.

15. Maresh M, Beard RW, Combe D, Dawson AM, Gillmer MDG, Smith G et al. Selection of

an obstetric data base for a microcomputer and its use for on-line production of birth

notification forms, discharge summaries and perinatal audit. Br J Obstet and Gyn 1983;

90:227-231.

Subchapter 42.4. Notifying Patients of Abnormal Results

Background

One of the most distressing safety issues of the clinical encounter is the failure to followup on diagnostic tests, particularly when a patient is not notified of an abnormal result. The

complexities of this problem are legion. Contact methods—whether by phone, mail, fax or email, and whether sent by the lab, clinic or individual clinician—vary widely in their reliability

(with most being imperfect). In some instances patients are told that if they do not hear back

regarding their test results it signifies normal results. Of course, not hearing may mean that the

test was lost or that the contact method was faulty. Other issues arise when the content of the

notification is not clear, either as to result or the recommended follow-up for re-testing or

treatment options.

This chapter evaluates safety practices aimed at improving patient notification of

abnormal results. Adequate medical and/or surgical care during follow-up is essential to

reducing patient morbidity and mortality, but practices to address this are beyond the scope of

patient safety as defined in this Report. We have chosen the example of Pap smear results,

although many of the issues should be transferable to other laboratory (eg, PSA level) and

radiologic (eg, mammogram) results.
483

Practice Description

Our search revealed only one study evaluating patient notification practices.1

 In this

study, the patient’s mailing address was included on the Pap smear request form. Two weeks

after the patient’s primary care provider received the results, the laboratory directly notified the

patient by mail. The notification was by form letter advising the patient of her results and

providing advice on the recommended follow-up step: discuss results with the doctor, return in

two years time, or make an appointment to see the doctor without delay.

Prevalence and Severity of the Target Safety Problem

Few data exist concerning physician follow-up and patient notification of abnormal

results. In a survey of attending physicians and residents practicing at a large urban teaching

hospital and 21 suburban primary care practices, virtually all respondents believed it was

moderately or extremely important to notify patients of abnormal results, yet 36% of physicians

did not always do so.2

 Among the most common reasons reported by physicians were

forgetfulness and inability to reach patients. One large cross-sectional study examined physician

documentation of notification to patients of abnormal mammograms, Pap smears, and

cholesterol tests. The results demonstrated that certain patient characteristics such as race,

language, and education may be associated with a failure to transmit abnormal results to

patients.3

An estimated 4600 American women died of cervical cancer in 2000.4 There are no data

regarding to what extent delays in notification result in worse patient outcomes, including

mortality. One study evaluating processes to reduce non-adherence rates with the follow-up of

abnormal Pap smears noted that many women (the exact number was not presented) reported

that they were never notified of their abnormal Pap smear result initially.5

Tracking systems for abnormal Pap smear results have been briefly mentioned in the

context of studies evaluating interventions to improve overall follow-up, not patient

notification.5,6 However, the effectiveness of these tracking systems was not specifically

evaluated so they are not reviewed here.

Opportunities for Impact

Compliance rates with follow-up medical care after abnormal Pap smears typically

ranges from 50% to 70%.5,7-9 It is unclear how often losses to follow-up resulted from failure to

notify. There are no data indicating how many practice groups directly mail abnormal Pap smear

results to patients. Even with successful patient notification practices, a corresponding reduction

in morbidity and mortality may not occur because of the other barriers to adequate follow-up

described in the literature.5,10

Study Design and Outcomes

The study reviewed for this chapter was a randomized control design (Level 1).1

 (Table

42.4.1). Providers were randomized into 2 groups. In the intervention group, the pre-cervical

smear questionnaire form had been redesigned to allow the patient to request that results be

mailed directly to her. The physicians in the intervention group determined which patients would

be offered direct notification. Patients of physicians in the control group were notified of results

using whatever protocol the provider typically used. The authors did not elaborate on the

methods used to notify patients in the control group.
484

The primary outcome was adherence with follow-up visits (Level 2), which was defined

by searching the laboratory records for evidence of a follow-up Pap smear one year after

notification. If a cervical smear result was not located through the laboratory database search

then the patient’s provider was contacted.1

Evidence for Effectiveness of the Practice

Significantly fewer women with cervical intraepithelial neoplasia (CIN) on Pap smear

who were randomized to the intervention group were lost to follow-up (0/52 vs. 9/39 in the

control group, p<0.001). In the group of women with atypia, 13% (15/116) were lost to followup in the intervention group and 10% (10/104) were lost to follow-up in the control (p=NS).

A limitation of this study was that providers decided who in the intervention group

actually received the intervention after randomization. Only 41% of patients in the intervention

group were actually mailed their results. However, analysis was performed with an intention-totreat design.

Potential for Harm

Although the patients in this study were not interviewed, other reports reveal that

psychological distress is common after notification of an abnormal Pap smear.11 Thus a potential

harm of this practice, or any practice to directly notify a patient of an abnormal result, could be

anxiety and distress that might be mitigated if a health practitioner were to deliver the

information.

Costs and Implementation

Buy-in of health care providers is an important aspect of practice implementation and

may be affected by the concern for potential harm and the specifics of the notification process. In

the Del Mar study, 23% of providers were unhappy with the wording of the letter.1

 Direct patient

notification systems require accuracy and reliability of the administrative database. One study

trying to improve adherence to follow-up after an abnormal Pap smear result was only able to

make telephone contact with 42% of the eligible patients.5

 They found that 16%-20% of their

telephone and address data were inaccurate.

Although patient tracking systems are not evaluated in this chapter because of the lack of

published literature, in one study clinical personnel stated that they were reluctant to perform the

tracking function of the intervention, and even discontinued the Pap smear log once the study

was completed.12

Comment

Failure to notify patients of abnormal results is a little-studied but major problem

involving both patient safety and health care quality. One study evaluated direct mailings of

abnormal results to patients and found improved follow-up in one subset of patients. More data

are required before recommending implementation of this practice.

We were unable to find any studies evaluating specific interventions aimed at providers

that resulted in increased notification to patients of abnormal results. Interventions that target

providers through computerized reminders linked with patient tracking systems might have an

impact on improving patient notification of abnormal results. This area is an important source of

future investigation.
485

Table 42.4.1. Randomized controlled trial of direct notification of abnormal Pap smear

results*

Study Study Setting Outcomes Results (95% Confidence Interval)†

Del Mar,

19951

311 women with abnormal

Pap smears from 42

general practices in

Australia

Level 2 Patients with CIN lost to follow-up:

Direct mail notification: 0 (0-0.07)

Control: 0.23 (0.11-0.39)

Patients with atypia lost to follow-up

Direct mail notification: 0.10

Control: 0.13 (p=NS)

* CIN indicates cervical intraepithelial neoplasia; NS, not statistically significant.

†

 Proportion of patients lost to follow-up reported in intervention group vs. control group.

References

1. Del Mar CB, Wright RG. Notifying women of the results of their cervical smear tests by

mail: does it result in a decreased loss to follow-up of abnormal smears? Aust J Public

Health 1995; 19:211-213.

2. Bookhaker EA, Ward RE, Uman JE, McCarthy BD. Patient notification and follow-up of

abnormal test results: a physician survey. Arch Intern Med 1996; 156:327-331.

3. Burstin HR, Puoplolo AL, Haas JS, Cook EF, Brennan TA. Patients at risk for missed

follow-up after abnormal tests [abstract]. J Gen Intern Med 13, 46A. 1998.

4. American Cancer Society. Cancer Facts & Figures 2000. Atlanta, GA . 2000.

5. Marcus AC, Kaplan CP, Crane LA, Berek JS, Bernstein G, Gunning JE et al. Reducing

loss-to-follow-up among women with abnormal Pap smears. Results from a randomized

trial testing an intensive follow-up protocol and economic incentives. Med Care 1998;

36:397-410.

6. Paskett ED, White E, Carter WB, Chu J. Improving follow-up after an abnormal Pap

smear: a randomized controlled trial. Prev Med 1990; 19:630-641.

7. Marcus AC, Crane LA, Kaplan CP, Reading AE, Savage E, Gunning J et al. Improving

adherence to screening follow-up among women with abnormal Pap smears: results from a

large clinic-based trial of three intervention strategies. Med Care 1992; 30:216-230.

8. Michielutte R, Diseker RA, Young LD, May WJ. Noncompliance in screening follow-up

among family planning clinic patients with cervical dysplasia. Prev Med 1985; 14:248-258.

9. Singer A. The abnormal cervical smear. Br Med J (Clin Res Ed) 1986; 293:1551-1556.

10. Stewart DE, Buchegger PM, Lickrish GM, Sierra S. The effect of educational brochures on

follow-up compliance in women with abnormal Papanicolaou smears. Obstet Gynecol

1994; 83:583-585.

11. Stewart DE, Lickrish GM, Sierra S, Parkin H. The effect of educational brochures on

knowledge and emotional distress in women with abnormal Papanicolaou smears. Obstet

Gynecol 1993; 81:280-282.

12. Paskett ED, Phillips KC, Miller ME. Improving compliance among women with abnormal

Papanicolaou smears. Obstet Gynecol 1995; 86:353-359.
486

Final Comment to Chapter 42

Faulty information transfer causes discontinuities of care that may result in adverse

events. However, interventions to improve information transfer have received relatively little

attention in the medical literature. Unfortunately, numerous barriers impede the appropriate

transfer of information between institutions and between patient and provider. Future

technologies that allow for more seamless transfer of information may mitigate these gaps in

patient care. Further evaluation is critical.
487

Chapter 43. Prevention of Misidentifications

Heidi Wald, MD

University of Pennsylvania School of Medicine

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

Subchapter 43.1. Bar Coding

Background

Machine-readable automatic identification (ID) systems, including bar codes, magnetic

stripes, optical character recognition and radiofrequency labeling, have improved productivity

and quality in diverse industries. Bar codes represent the oldest and most common of these

machine-readable ID systems,1,2 and are widely used in industrial manufacturing, shipping and

inventory tracking operations. Prior to bar coding, these processes would have involved

keystroke entry of identification numbers, producing approximately one error in every 300

entered characters. In contrast, bar coding produces misidentification errors at rates ranging from

one character in 15,000 to one character in 36 trillion.3

The use of bar coding in health care was first described over 30 years ago in clinical

laboratories and blood banks.1,4 In 1984, Rappoport identified 3 areas for the use of automatic ID

technology in lab medicine: patient identification, document identification, and specimen

identification.1

 However, in a 1987 survey by the American Hospital Association, the use of bar

codes was most widespread in materials management departments, rather than in clinical

application.5

 Other areas in which hospitals employed bar codes at that time included the clinical

laboratory, pharmacy, radiology, medical records and asset management. Despite the Health

Industry Bar Code Council’s call for standardization in the mid-1980s, the implementation of bar

code technology has been stymied by lack of industry standards and failed cooperation among all

stakeholders.2,6

As bar coding has the potential to substantially increase productivity and accuracy, one

would expect it to be applied to important patient safety practices. Unfortunately, the published

literature contains very little evidence regarding health care applications. In this chapter we focus

on 4 areas in which bar coding shows promise for improving patient safety: patient

identification, medication dispensing and administration, specimen handling, and medical record

keeping.2,7-10

Practice Description

Patient Identification

Machine-readable patient ID systems could replace conventional wrist-banding, and

might reduce patient ID errors ranging from specimen collection to medication and blood

product administration. Attempts to create such machine-readable ID systems were reported in

the blood banking literature as early as 1977.11 Transfusion Medicine is particularly attuned to

issues of patient identification, as specimen collection and blood product administration account

for the majority of preventable transfusion errors.12,13

Most scenarios for patient identification involve the substitution or supplementation of

the traditional wristband for one with a unique bar code patient identifier. All patient specimens,

medications and released blood products then receive the patient’s unique bar code ID. No
488

procedure or treatment can occur unless the patient’s ID is scanned with a portable scanner and

matched with a bar code generated by the doctor’s order. For example, a phlebotomist would

carry the scanner, check the patient’s ID against a bar coded specimen label or collection list,

and draw blood only in the event of a match. Similarly, for administration or treatment, the

patient’s ID and the intended therapeutic would be scanned at the bedside with a portable reader.

If a match exists, the transfusion or medication is allowed and the time and date are recorded and

even transmitted directly to the hospital computer system. The nurse’s bar code ID can also be

scanned and a timed administration record can be created. If there is no match, an alarm is

sounded, and the administration delayed until the problem is resolved. 9,14

Other technological means to reduce error in patient identification have been examined in

the transfusion literature. Several researchers explored the use of a system providing a

mechanical barrier to transfusion through a series of locks.15 This system appears to be

cumbersome and easily circumvented. In addition, electronic blood banking, with point-of-care

crossmatching and computer-controlled release of blood, has been examined for high volume

transfusion areas such as the operating room or intensive care unit.16 Due to major barriers to

large-scale implementation, these practices will not be discussed further.

Specimen handling

Clinical laboratories have integrated bar codes in specimen handling with a great deal of

success.3,8 Several authors have described the development of central laboratory information

systems (LIS) that employ bar code technology. Collection list and label software can be

modified to integrate and produce bar coded information. Confirmation of labeling and patient

ID occurs at the bedside. Specimen sorting and aliquoting in the laboratory can be shortened or

eliminated by various setups. At Rush-Presbyterian Hospital in Chicago, a central receiving

station rapidly sorts and aliquots bar coded samples as they move on a conveyor belt.3

 At the

University of Kansas Medical Center, the collection tubes are also used for analysis, thus

eliminating the need for aliquoting samples. Additionally, the computer sends the bar codecoordinated orders to each of the 2 chemistry analyzers. Because a sample can then be

appropriately processed at either analyzer, the need for sorting samples has also been

eliminated.8

 Clinical labs also employ bar code technology in harder-to-automate processes. For

instance, the University of Utah uses bar codes to replace common keystrokes for text reporting

of microbiology results—eg, a technician might use a bar code “pick list” to scan the single bar

code that means “no growth for 24 hours” and eliminate the need to type this phrase.17,18

Medication dispensing and administration

The use of bar codes is uniquely suited to the dispensing and administration stages of the

medication process.19 Bar coding may be used to simplify the patient cassette (the medicine tray

for bedside delivery) filling and verification process.20 For instance, a technician fills a cassette

according to a computerized, bar coded medication schedule and completes a quick verification

by scanning the label of each unit-dose that has been placed in it with a handheld scanner. The

computer can generate an error message if an incorrect medication is entered. The administration

of bar coded medications can also be tracked at the point-of-care using a portable scanner and

compared against the hospital computer’s medication orders.9,21 Bar coded medication

administration has the added capability of creating a record of the administration (ie, RN, date,

time) and a bill. This type of system could be integrated with a patient identification system in an

attempt to eliminate errors resulting in administration of medication to the wrong patient.
489

Medical record keeping

Radiology and medical records departments use bar code technology to track the location

and status of studies and charts.22-24 Even more creative use of bar coded information has been

reported in the emergency medicine and pharmacy literatures. As with the applications in the

microbiology lab, bar codes can be used to replace frequently used text for the creation of

medical records. “Pick lists” of bar codes with their text equivalents can be employed in

circumstances requiring speed and accuracy. Several uses of bar coded scripts have been

examined in resuscitation events, and in mass casualty recording.10,25-27 The use of bar code

“pick lists” for the documentation of pharmacists’ clinical activities has also been explored.28-30

Prevalence and Severity of the Target Safety Problem

Bar code technology may be used to address any number of patient safety issues in

medicine. For this discussion, we will define the target safety problem as patient identification in

general, using transfusion medicine as a specific example.

Patient identification remains a challenge in hospitals because of the number of complex

interventions that occur to patients ranging from meals to surgeries. These interventions occur in

a variety of locations and are provided by large teams of staff who work in shifts. In addition,

sick patients, or those who have a language barrier, are not always capable of responding to

questions about their identity or treatment plans. Hospitals generally rely on standardized

wristbands containing the patient’s name and other identifying information such as medical

record number or date of birth. Unfortunately, conventional wristbands are not reliable sources

of patient identification. A 1991 national sample of 712 hospitals estimated error rates for

conventional patient identification wristbands to be 5.5%.31 In half of the errors, the patient’s

wristband was absent altogether. The error rates were significantly lower in hospitals where

phlebotomists had responsibility for monitoring wristband accuracy, as the phlebotomy staff

would not perform routine lab work unless the band was corrected. Other errors included more

than one wristband with conflicting data (18.3%); wristbands with incomplete (17.5%),

erroneous (8.6%), or illegible data (5.7%); and rarely, patients wearing wristbands with another

patient’s data (0.5%). As patient identification data are only as good as the information entered

at registration, the use of bar coded ID data could not be expected to correct certain types of

errors such as a wristband with incorrect data entered at admission, although it is potentially

beneficial in eliminating other types of errors such as illegible data. 

Even when wristbands are free of errors, protocols for patient identification (such as dual

witness verification of identification for blood transfusion) are easily circumvented or performed

incorrectly.32 In an analysis of major transfusion errors reported to the FDA over a 10-year

period from 1976-1985, Sazama found 10 patient deaths where the actual and intended patients

shared the same last name, and 5 deaths where the 2 shared the same hospital room.13

Consequently, automatic patient identification systems have been proposed as a technological

solution to remove human factors (Subchapter 41.1) from the patient identification process.

Despite technical improvements in testing for blood group identification, fatal ABOincompatible transfusions in the United States continue to occur at a rate ranging from

approximately 1:600,000 to 1:800,000, with as many as two dozen fatalities in the US

annually.12,13 Thus, the chance of a patient suffering a fatal transfusion reaction due to ABOincompatibility is roughly equivalent to the risk of acquiring HIV infection from a blood

transfusion.33,34 Patient misidentification represents the most common cause of ABOincompatible transfusion, accounting for 46-57% of these errors.12,13 Since the rate of patient and
490

donor having blood group compatibility by chance is approximately 60%, it is estimated that the

total number of ABO-incompatible transfusions is much higher than the rate of fatal errors. A

study from New York State estimated that as many as one in 12,000 transfusions involve

administration of a blood product intended for another patient or release of blood of an incorrect

group.*12

Opportunities for Impact

 The implementation of automatic patient identification may present a large opportunity

to bring transfusion medicine and other hospital interventions closer to the goal of zero risk.

According to a survey conducted by the American Society of Hospital-System Pharmacists,

1.1% of responding hospitals use bar coding of drug products in conjunction with bar coding on

the patient’s identification tag.35

Study Designs

Multiple reports of the use of bar codes appear in the medical literature, but most of these

relate to inventory management. Few authors examine bar codes for patient identification. Only

one of these studies was a prospective evaluation, and in the study bar coded patient

identification comprised only one small part of the intervention.10 One observational study

examined a bar code patient ID system for medication administration.9

 In the study, however,

routine patient ID scanning was easily circumvented and the actual error rate was not provided.

The remainder of the reports are descriptive in nature.14,36,37 Therefore, error rates in automated

patient identification could not be readily compared to usual practice.

The use of bar coding in other clinical care applications (aside from inventory control)

has been examined prospectively in trauma recording27 and in documenting pharmacists’

interventions.28 One additional observational study examined bar coding in pharmacy

dispensing.20

 

*This is based on a reported error rate of 1/19,000 transfusions. The authors estimate a 64%

chance that a random transfusion to an unintended recipient would be compatible and assume

100% reporting of incompatible erroneous transfusions
491

Study Outcomes

Some of the studies report error rates in transfusion or medication errors (Level 2), while

others report related outcomes such as speed of data entry (Level 3), transcription errors (Level

2) in a variety of experimental and clinical settings, and user satisfaction (Level 3).

Evidence for Effectiveness of the Practice

A point-of-care information system for medication management was implemented at a

tertiary care center in Colorado.9

 The system provided online patient and medication data that

verified medication administration at bedside using hand-held scanners to record patient ID,

nurse ID, and medication unit-dose bar codes. When intervention data were compared with

historical controls, the pre-intervention medication error rate of 0.17% dropped to 0.05%,

sustained over 3 years for an overall decrease of 71% (p value not reported). There was a 33%

decrease in "wrong drug" errors, a 43% decrease in "wrong time" errors, and a 52% decrease in

"omitted dose" errors. There was a 47% decrease in "transcription/order-entry" errors. There was

no change in "wrong patient" errors or "wrong dosage" errors, perhaps because the component of

the multifaceted intervention most likely to mitigate these errors, the use of the scanners for

patient ID, was easily and frequently circumvented. It is unclear if bedside scanning added an

unwanted layer of work for the nurses, or if they were uncomfortable performing this task in

front of patients and families. Computerized pharmacy and bar code tracking of medications led

to qualitative improvements in documentation time, scheduling of administration, nursingpharmacy communications, and pharmacist drug monitoring. However, the contribution of bar

coding to the decreased error rate is not distinguishable from that of the entire intervention. It

also appears that the point-of-care patient ID portion of the intervention was easily bypassed, and

was therefore not adequately evaluated.9

On a large medical ward of a university hospital, the satellite pharmacy was reconfigured

to implement bar code technology for drug dispensing.20 The hospital bar coded all medications,

patient medication cassettes, patient wristbands, and employees. Standard dispensing time was

estimated at 8.24 seconds, while dispensing time for bar coded medications was 6.72 seconds (p

value not reported). Accuracy of the standard cassette fill system was 99.6% (equivalent to one

error in 250 doses), while the accuracy of bar coded cassette fill was reported to be 100% (based

on 0 errors in about 20,000 doses). The pharmacists were freed to do other work as the burden of

dispensing was shifted to pharmacy technicians.

As pharmacists have begun to use bar code technology for medication distribution, 2

pharmacy groups described the use of bar codes in recording their clinical interventions.28, 29 One

group found bar code documentation to have lower overall error rates compared to manual

documentation, while the marginal cost of implementing bar coding was less than $100

(factoring in savings in labor costs related to manual entry).28 These data were limited by the

small number of operators who differed on their preferences for manual versus bar code

recording.

A prospective trial reviewed bar code technology in trauma recording. Experienced

emergency room nurses found bar coded pick lists to be easy to use and produced fewer errors

per record compared with handwriting (2.63±0.24 vs. 4.48±0.3, p<0.0001) for videotaped trauma

resuscitations.27 In a prospective study of simulated mass casualty incidents in The Netherlands,

bar coded computer registration produced 25% fewer inaccuracies than handwritten medical

charts.10
492

The limitations of these studies are numerous, including their small sample sizes and lack

of generalizability. However they demonstrate that bar code technology is generally easy for

operators to use, can be applied in a variety of creative ways, and produces easy-to-demonstrate

gains in accuracy and efficiency.

Potential for Harm

There is no clear detriment to patient identification with a bar code system. However, as

with the addition of any new technology, the possibility exists that the complexity of the

information system, especially if it grows, could create more routes for potential failure. For

instance, an error during patient registration might be perpetuated throughout the hospitalization

by the information systems, and be more difficult to correct than with conventional systems. The

system’s data are only as accurate as that entered by fallible humans.

Costs and Implementation

Significant barriers need to be overcome before the full potential of bar coding can be

exploited in the clinical setting. The process of medication dispensing and administration

highlight several examples of these barriers. First, pharmaceutical manufacturers have yet to

adopt a universal bar code standard like the UPC system used in grocery store inventory.38 As of

yet, there has been no regulatory mandate by the FDA to serve as an incentive, although the

American Society of Hospital-System Pharmacists recently urged the FDA to take action.39

Second, placing bar codes on unit-doses of medications often requires major changes in

packaging (such as an increase of the package size to accommodate the bar coded label). Bar

code tracking systems would have difficulty with unusual doses such as halved tablets. IV doses

would still require bar code labeling in the pharmacy when prepared. 

At this point, implementation of bar coding requires a commitment on the part of the

hospital to relabel every unit-dose of medication using a hospital standard. The hospital

pharmacies that have implemented these systems have repackaged and relabeled many unitdoses at considerable cost.9,20 One health system estimated costs at $119,516 annually, with the

per dose costs of bar code labeling estimated at 2.73 cents.20 The bottom line is that, at present,

the costs of implementing bar coding in an entire pharmacy inventory are significant and the

logistics complex.

The use of bar coding in simpler clinical scenarios (ie, using a blood transfusion

wristband for patient identification) may be implemented with very modest outlay of resources

(estimated to be less than 5 cents per wristband).36 The costs of the scanners themselves are

moderate. A new model scanner, software and recharger were priced at about $1100 in 1997.28

Comment

Bar coding is a fast and accurate method of automated data capture that in experimental

settings provides qualitative improvements in speed and accuracy of data entry. Bar code

technology might be creatively applied to any number of data-driven processes in medicine. As

the rapid and accurate transfer of data is paramount in health care, the thoughtful application of

appropriately piloted and evaluated bar code technology is likely to be well received and

deserves further investigation.
493

References

1. Rappoport A. A hospital patient and laboratory machine-readable identification system

(MRIS) revisited. J Med Syst. 1984;8:133-156.

2. Weilert M, Tilzer LL. Putting bar codes to work for improved patient care. Clin Lab Med.

1991;11:227-238.

3. Maffetone MA, Watt SW, Whisler KE. Automated sample handling in a clinical

laboratory. Comput Healthc. 1988;9:48-50.

4. Brodheim E, Ying W, Hirsch R. An evaluation of the codabar symbol in blood bank

automation. Vox Sang. 1981;40: 3.

5. Longe K. The status of bar codes in hospitals: a survey report. Hospital Technology Series.

Chicago: American Hospital Association; 1989. 8.

6. Garza D, Murdock S, Garcia L, Trujillo JM. Bar codes in the clinical laboratory. Clin Lab

Sci. 1991;4:23-25.

7. Zarowitz BJ, Petitta A, Rudis MI, Horst HM, Hyzy R. Bar code documentation of

pharmacotherapy services in intensive care units. Pharmacotherapy. 1996;16:261-266.

8. Tilzer LL, Jones RW. Use of bar code labels on collection tubes for specimen management

in the clinical laboratory. Arch Pathol Lab Med. 1988;112:1200-1202.

9. Puckett F. Medication-management component of a point-of-care information system. Am

J Health-Syst Pharm. 1995;52:1305-1309.

10. Noordergraff G, Bouman J, Van Den Brink E, Van De Pompe C, Savelkoul T.

Development of computer-assisted patient control for use in the hospital setting during

mass casualty incidents. Am J Emerg Med. 1996;14:257-261.

11. Sherer P, Chambers R, Taswell H, Altshuler C, Aster R, Covino K, et al. Automated donorrecipient identification systems as a means of reducing human error in blood transfusion.

Transfusion. 1977;17:586-597.

12. Linden J, Paul B, Dressler K. A report of 104 transfusion errors in New York State.

Transfusion. 1992;32:601-606.

13. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion.

1990;30:583-590.

14. Jensen N, Crosson J. An automated system for bedside verification of the match between

patient identification and blood unit identification. Transfusion. 1996;36:216-221.

15. Wenz B, Burns E. Improvement in transfusion safety using a new blood unit and patient

identification system as part of safe transfusion practice. Transfusion. 1991;31:401-403.

16. Cox C, Enno A, Deveridge S, Seldon M, Richards R, Martens V, et al. Remote electronic

blood release system. Transfusion. 1997;37:960-964.

17. Aller R, Freidman W. Rapid accuate entry of microbiology results. Arch Pathol Lab Med.

1996;120:57-61.

18. Willard K, Stanholtzer C. User interface reengineering: Innovative applications of bar

coding in a clinical microbiology laboratory. Arch Pathol Lab Med. 1995;119:706-712.

19. Bates D. Using information technology to reduce rates of medication errors in hospitals.

BMJ. 2000;320:788-791.

20. Meyer G, Brandell R, Smith J, Milewski F, Brucker J, P, Coniglio M. Use of bar codes in

inpatient drug distribution. Am J Hosp Pharm. 1991;48:953-966.

21. Gebhart F. VA slashed drug erros via bar-coding. Drug Topics. 1999; 143: 44.

22. Mudie D. Bar coding in a medical records department: a case study. Hosp Technol Ser.

1988;7:1-15.
494

23. Arenson RL, London JW. Comprehensive analysis of a Radiology Operations Management

computer system. Radiology. 1979;133:355-362.

24. Connelly A. Bar codes help control incomplete medical records. J Am Med Rec Assoc.

1987;58:48-49.

25. Burt TW, Bock HC. Computerized mega code recording. Ann Emerg Med. 1988;17:339-

342.

26. Bock HC. Field verification methodology using bar coding to record data. Ann Emerg Med.

1993;22:75-8; discussion 78-79.

27. Chua R, Cordell W, Ernsting K, Bock H, Nyhuis A. Accuracy of bar codes versus

handwriting for recording trauma recuscitation events. Ann Emerg Med. 1993;22:1545-

1550.

28. Kanmaz T, Haupt B, Peterson A. Comparison of manual and bar-code systems for

documenting pharmacists' interventions. Am J Health-Syst Pharm. 1997;54:1623-1626.

29. Zarowitz B, Petitta A, Mlynarek M, Touchette M, Peters M, Long P, et al. Bar-code

technology applied to drug use evaluation. Am J Hosp Pharm. 1993;50:953-959.

30. Scott M, McElnay J, Burnett K. Using bar-code technology to capture clinical intervention

data in a hospital with a stand-alone pharmacy computer system. Am J Health-Syst Pharm.

1996;53:651-654.

31. Renner S, Howanitz P, Bachner P. Wristband identification error reporting in 712

hospitals. Arch Pathol Lab Med. 1993;117:573-577.

32. Feldman S, Roblin D. Medical accidents in hospital care: applications of failure analysis to

hospital quality appraisal. Jt Comm J Qual Improv. 1997;23:567-580.

33. Schreiber G, Busch M, Kleinman S, Korelitz J. The risk of transfusion-transmitted viral

infections. The Retrovirus Epidemiology Donor Study. N Engl J Med. 1996;334:1685-

1690.

34. Lackritz J, Satten G, Alberle-Grasse J, al e. Estimated risk of transmission of the human

inmmunodeficiency virus by screened blood in the United States. N Engl J Med.

1995;333:1721-1725.

35. American Society of Hospital-System Pharmacists. National survey of pharmacy practice

in acute care settings: dispensing and administration - 1999. Am J Health-Syst Pharm.

2000;57:1759-1775.

36. Lau F, Wong R, Chui C, Ng E, Cheng G. Improvement in transfusion safety using a

specially designed transfusion wristband. Transfusion Medicine. 2000;10:121-124.

37. Amber R, Everett V. Emergency department patient tracking: A cost-effective system

using bar code technology. J Emerg Nurs. 1996;22:190-195.

38. Davis NM. Initiative for reducing medication errors: the time is now. Am J Hosp Pharm.

2000;57:1488.

39. American Society of Hospital-System Pharmacists. ASHP policy recommendation. Am J

Health Syst Pharm. 2001;58:603-606.

Subchapter 43.2. Strategies to Avoid Wrong-Site Surgery

Background

Operating on the wrong site or body part represents a potentially devastating event for all

parties involved. Cases of “wrong-site surgery” frequently attract considerable media attention1-4

and foment malpractice lawsuits. Claims for wrong-site orthopedic surgeries result in indemnity
495

payments in 84% of cases, compared with only 30% of orthopedic claims overall.5,6 Although

orthopedics represents the largest source of legal claims, the Physician’s Insurance Association

of America (PIAA) has handled wrong-site surgery litigation from the entire range of surgical

specialties and subspecialties.6

 Common factors identified in wrong-site surgery include the

involvement of multiple surgeons on a case, the performance of multiple procedures during a

single trip to the operating room, unusual time constraints, and unusual anatomy or patient

characteristics, such as physical deformity or morbid obesity.7,8

Based upon careful review of 43 cases reported through its Sentinel Event Policy9 over a

3-year period, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO)

issued the following recommendations for avoiding wrong-site surgery:7,8

• Mark the operative site and involve the patient in this process

• Require oral verification of the correct site in the operating room by each member of

the surgical team

• Follow a verification checklist that includes all documents and medical records

referencing the intended operative procedure and site

• Directly involve the operating surgeon in the informed consent process

• Engage in ongoing monitoring to ensure verification procedures are followed

Among these recommendations, marking the operative site has received the most

attention and is the focus of this chapter.

Practice Description

In 1998, the American Academy of Orthopaedic Surgeons endorsed a program of

preoperative surgical site identification called “Sign your Site,” modeled on the “Operate

through your initials” campaign instituted by the Canadian Orthopaedic Association from 1994-

96.5,10 Both organizations recommend that the operating surgeon initial the intended operative

site, using a permanent marker, during a scheduled preoperative visit. For spinal surgery, the

recommendations additionally endorse the use of intra-operative x-rays for localization of the

pathologic spinal level before proceeding with the procedure. Many surgeons already employ

their own techniques for surgical site identification such as marking an “X” on the operative site

or marking “No” on the wrong limb.5,11,12 While these practices are commendable, they have

theoretical drawbacks including lack of standardization across operating rooms and institutions.

These alternative strategies will not be evaluated further in this chapter.

Prevalence and Severity of the Target Safety Problem

From January 1995 to March 2001, JCAHO reviewed voluntary reports of 1152 “sentinel

events.” Wrong-site surgery accounted for 114 (9.9%) of these reports and included procedures

in neurosurgery, urology, orthopedics, and vascular surgery.13 Despite the high profile of

JCAHO’s Sentinel Event Policy,9

 under-reporting by health care organizations almost certainly

affects these statistics. Only 66% of the 1152 total events were “self-reported” by the institutions

involved. The remainder came from patient complaints, media stories and other sources.13 In

fact, using a mandatory reporting system, the New York State Department of Health received 46

reports of wrong-site surgery from April 1, 1998 through March 31, 20004

 (F. Smith, personal

communication, May 2001), compared with the 114 cases JCAHO received nationally over a
496

period 3 times longer.13 This suggests that voluntary incident reporting may underestimate the

true incidence by a factor of 20 or greater.14†

The PIAA reviewed claims data from 22 malpractice carriers representing 110,000

physicians from 1985 to 1995.5

 These claims included 331 cases of wrong-site surgery. The

complete PIAA database documents almost 1000 closed malpractice claims involving wrong-site

surgery.6

 However, this figure also underestimates the prevalence of wrong-site surgery, as every

case does not result in a claim. Most wrong-site surgeries involve relatively minor procedures

such as arthroscopy,10,15 rather than limb amputations or major neurosurgical procedures.

Consequently sequelae are minimal. The State Volunteer Mutual Insurance Company

(Tennessee) released a series of 37 wrong-site surgery claims from 1977 to 1997.15 Performing

the correct procedure on the wrong side constituted the most common error (eg, arthroscopic

knee surgery on the wrong knee in 15 of the 37 cases). Twenty-six of the patients experienced no

sequelae beyond a scar, and only three patients suffered permanent disability. Given the rarity of

significant harm, estimates of the incidence of wrong-site surgery derived from litigation data

likely underestimate the true prevalence of this problem, as do estimates based on incident

reports.

Opportunities for Impact

Some surgeons have developed their own methods for surgical site identification,11,12 but

routine preoperative evaluation and marking of the intended surgical site by the attending

surgeon has yet to become standard practice in orthopedics or any surgical specialty. One year

after its "Sign Your Site" campaign, the American Academy of Orthopaedic Surgeons surveyed

its membership. Among the 2000 orthopedic surgeons surveyed, 77% responded that the idea

was a good one, but only 40% stated that they complied with the recommended practice. Only

one-third stated that their principal hospitals had a “Sign Your Site” or similar program in place,

although many anticipated initiation of one in response to the campaign.16,17

Study Designs

The published literature includes no studies in which the adoption of a practice related to

surgical site identification is analyzed in the setting of a controlled observational design or

clinical trial. One report described the experience of 4 orthopedic surgeons in private practice,18

but included no comparable observations from a control group. The experience of the Canadian

Orthopaedic Association remains unpublished, and the observed effect is based entirely on

litigation statistics10 (B. Lewis, personal communication, March 2001).

Study Outcomes

Given the egregious and distressing nature of wrong-site surgery, the error itself

represents the outcome of interest, regardless of the clinical outcome. Unfortunately, in the

absence of observational studies that include controls, the number of malpractice claims for

wrong-site surgery represents the most widely cited outcome.

 

† Mandatory New York reporting system (NYPORTS) documented 46 events in 24 months.

New York State has a population roughly 1/15th of the entire country. Thus, had JCAHO

captured wrong-site surgeries with the same sensitivity, one would expect 2484 wrong site

surgeries to have been reported during the 87 months covered by the JCAHO sentinel event

policy. This figure is 21 times the actual figure of 114 cases. 
497

Evidence for Effectiveness of the Practice

The Canadian Medical Protective Association reported a baseline level of litigation for

wrong-site surgery at 7% of all orthopedic surgery settlements before 1994 when the Canadian

Orthopaedic Association instituted their “Operate Through Your Initials” policy.10 Currently,

there are no known wrong-site surgery claims against orthopedic surgeons in Canada. (B. Lewis,

personal communication, March 2001) Interpreting the difference in the rates of litigation of a

rare occurrence is difficult, however, especially without an accurate estimate of the denominator

(ie, the total number of relevant procedures performed during the time periods involved).

Moreover, the degree to which Canadian surgeons complied with the policy is unknown. As

mentioned above, only 40% of responding American orthopedists reported adoption of

preoperative site identification in routine practice.16

In a North Dakota private practice that used preoperative site identification with indelible

ink, there was one incidence of wrong-site surgery (pinning of the wrong phalanx in a hand) in

15,987 consecutive cases.18 Even assuming that the sole detected case represents the only wrongsite surgery in this sample, interpreting this low event rate is impossible without a control group.

Comparing this result with national data is also problematic. National data on the number of

orthopedics procedures performed each year might generate an estimate of an appropriate

“denominator,” but the nationwide “numerator” is unknown. Because we do not know the extent

to which incident reporting and malpractice litigation underestimate the incidence of wrong-site

surgery, we cannot accurately estimate the baseline rate of wrong-site surgeries for comparison

with results of a case series such as the North Dakota report cited above.18

Potential for Harm

Some surgeons may worry that marking the surgical site increases the risk of

contamination, but this concern appears unwarranted.15,18 More concerning is the potential harm

that may arise from confusion caused by practice variability in “signing the site.” Although the

original recommendations called for surgeons to initial the intended operative site, some

surgeons and hospitals mark the site with an “X.”

15,16 Still others use an “X” or “No” to mark the

limb or site that should not be operated upon.11,12 In addition, there are reports of patients

crossing their legs before the ink is dry and producing an identical mark on the contralateral

knee, thus subverting the intended effect of the intervention.10 Confusion may also ensue if

operating room personnel cover the mark with surgical drapes prior to the start of the surgery.10

Costs and Implementation

The costs of marking a surgical site are negligible. Marking procedures that require the

presence of the surgeon in the preoperative area prior to the initiation of anesthesia may require a

culture shift among surgeons and involve the costs of surgeons’ time. Implementation strategies

designed to more efficiently utilize the operating surgeon’s time could be designed. For

hospitalized patients, implementation might involve the operating surgeon initialing the intended

operative site at the time consent is obtained, thus requiring that the physician be present at the

time of consent. The nurse/anesthetist, anesthesiologist or other responsible party in the preop

area would then be required to contact the operating surgeon only in cases where the operative

site has not already been initialed.
498

Comment

While “signing the site” represents a low-tech solution with high face validity, no

evidence supports a particular version of this practice. Additionally, the existence of different

versions of the “signing the site” practice may cause confusion to the point of increasing the

likelihood of error. Strategies that focus only on a single aspect of the identification problem,

without considering the preoperative and operative processes as a whole may fail to avert error.

For instance, protocols that rely on review of key preoperative x-rays in the operating room

creates a new mandate to ensure that the correct patient’s x-rays are brought to the operating

room.6

Practices to successfully reduce (and eventually eliminate) wrong-site surgeries will

likely combine a standard method of marking the intended site with collaborative protocols for

verification of the intended procedure and operative site by all members of the operating room

staff.7

 Straightforward as each of these processes may appear, successful implementation may

require substantial investments of time and resources for protocol development and team

training. Whatever multifaceted practice is developed should be implemented within the setting

of a planned observational study.

References

1. Patient's son says family was seeking the best care (family of Rajeswari Ayyappan, who

had the wrong side of his brain operated on at Memorial Sloan-Kettering Cancer Center,

discusses his health). New York Times. Nov 16 1995: A16(N), B4(L).

2. Olson W. A story that doesn't have a leg to stand on (amputation of man's left leg rather

than right one may have been medically justified). Wall Street Journal. March 27 1995:

A18(W), A20(E).

3. Altman LK. State fines Sloan-Kettering for an error in brain surgery (New York State fines

Memorial Sloan-Kettering Cancer Center; surgeon operates on wrong side of patients

brain). New York Times. March 9 1996: 27(L).

4. Steinhauer J. So, the brain tumor's on the left, right? (Seeking ways to reduce mix-ups in

the operating room; better communication is one remedy, medical experts say). New York

Times. April 1 2001: 23(N), 27(L).

5. American Academy of Orthopaedic Surgeons. Advisory statement on wrong-site surgery.

Available at: http://www.aaos.org/wordhtml/papers/advistmt/wrong.htm. Accessed April

16, 2001.

6. Prager LO. Sign here. Surgeons put their signatures on patients' operative sites in an effort

to eliminate the change of wrong-site surgeries. Am Med News. October 12 1998: 13-14.

7. The Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Alert.

Lessons Learned: Wrong Site Surgery. Available at: http://www.jcaho.org/edu_pub/

sealert/sea6.html. Accessed March 30, 2001.

8. Lessons learned: sentinel event trends in wrong-site surgery. Jt Comm Perspect.

2000;20:14.

9. Sentinel events: approaches to error reduction and prevention. Jt Comm J Qual Improv.

1998;24:175-86.

10. Position paper on wrong-sided surgery in orthopaedics. Winnepeg, Manitoba: Canadian

Orthopaedic Association Committee on Practice and Economics; 1994.

11. Lubicky JP. Wrong-site surgery. J Bone Joint Surg Am. 1998;80:1398.
499

12. Cowell HR. Wrong-site surgery. J Bone Joint Surg Am. 1998;80:463.

13. Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Statistics.

Available at: http://www.jcaho.org. Accessed April 16, 2001.

14. U.S. Census Bureau. United States Census 2000: Ranking Tables for States: Population in

2000 and Population Change from 1990 to 2000. Available at:

http://www.census.gov/population/www/cen2000/phc-t2.html. Accessed May 31, 2001.

15. American Academy of Orthopaedic Surgeons. Report of the task force on wrong-site

surgery. Available at: http://www.aaos.org/wordhtml/meded/tasksite/htm. Accessed March

15, 2001.

16. Risk Management Foundation of the Harvard Medical Institutions. Did Wrong-Site

Surgery Remedy Work? Available at: http://www.rmf.harvard.edu/publications/resource/

feb1999news/article2/. Accessed April 16, 2001.

17. The American Academy of Orthopedic Surgeons. Academy News. "Sign your site" gets

strong member support. Available at: http://www.aaos.org/wordhtml/99news/os3-sign.htm.

Accessed May 5, 2001.

18. Johnson PQ. Wrong site surgery in orthopaedics: analysis of 15,987 cases at The

Orthopaedic Instititute in Fargo. Paper presented at: American Academy of Orthopaedic

Surgeons 67th Annual Meeting; March 15, 2000, 2000; Los Angeles, CA.
500
501

Chapter 44. Crew Resource Management and its Applications in Medicine

Laura Pizzi, PharmD

Neil I. Goldfarb

David B. Nash, MD, MBA

Thomas Jefferson University School of Medicine

and Office of Health Policy & Clinical Outcomes

Background

Patient care, like other technically complex and high risk fields, is an interdependent

process carried out by teams of individuals with advanced technical training who have varying

roles and decision-making responsibilities. While technical training assures proficiency at

specific tasks, it does not address the potential for errors created by communicating and decision

making in dynamic environments. Experts in aviation have developed safety training focused on

effective team management, known as Crew Resource Management (CRM). Improvements in

the safety record of commercial aviation may be due, in part, to this training.1

 Over the past 10

years, lessons from aviation’s approach to team training have been applied to patient safety,

notably in intensive care unit (ICU) and anesthesia training.2,3 This chapter reviews the literature

on Crew Resource Management, also known as Cockpit Resource Management, and describes

adaptations of this training framework to medicine.

Practice Description

Crew Resource Management in Aviation

Crew Resource Management has been widely used to improve the operation of flight

crews. The concept originated in 1979, in response to a NASA workshop that examined the role

that human error plays in air crashes.4

 CRM emphasizes the role of human factors in high-stress,

high-risk environments. John K. Lauber, a psychologist member of the National Transportation

Safety Board, defined CRM as “using all available sources—information, equipment, and

people—to achieve safe and efficient flight operations.”

5,6 CRM encompasses team training, as

well as simulation (also referred to as Line-Oriented Flight Training, or LOFT), interactive

group debriefings, and measurement and improvement of aircrew performance.

There is no universal CRM training program. The Federal Aviation Administration

(FAA) allows air carriers to customize their CRM programs to best suit the needs of individual

organizations. Therefore, training programs vary somewhat from carrier to carrier, making it

difficult to describe operational components. Furthermore, these programs continue to evolve as

aviation technology changes and more is learned about group dynamics.

One CRM model focuses on the elements of human effectiveness.7

 The 3 primary

components of effective crew management are safety, efficiency, and morale. Specific factors

related to aircrew performance are categorized, and serve as the basis for training and research.

These factors include materials, organization, individual, and group process variables associated

with performance.8

 Examples of outcomes that result from these input variables are safety,

efficiency, and customer satisfaction.

Subsequently, Helmreich and colleagues proposed a modified conceptual framework for

CRM, termed the “Error Troika,”

9

 to display a hierarchy of 3 error countermeasures. At the first
502

level, CRM includes training on how to avoid errors. At the second level, potential errors are

“trapped” before they are committed. At the third level, mitigation of error consequences occurs.

From a practical standpoint, CRM programs typically include educating crews about the

limitations of human performance.10 Trainees develop an understanding of cognitive errors, and

how stressors (such as fatigue, emergencies, and work overload) contribute to the occurrence of

errors. Multi-day CRM training programs typically require participants to assess personal and

peer behavior. Operational concepts stressed include inquiry, seeking relevant operational

information, advocacy, communicating proposed actions, conflict resolution and decision

making.

Prevalence and Severity of the Target Safety Problem

The field of aviation has a substantial history of collecting and analyzing safety-related

data. Historically, human error has caused or contributed to over 50% of aviation accidents. In an

analysis of 35,000 reports of incidents over 7.5 years, almost 50% resulted from a flight crew

error, and an additional 35% were attributed to air traffic controller error.11 Root cause analyses

(Chapter 5) by safety experts have found that errors frequently occur because flight crews fail to

effectively manage the resources available to them (eg, fail to verify information when uncertain

about it, fail to plan for contingencies).11 Naval aviation reports provide similar results, with one

study reporting 59% of “Class A mishaps” (serious consequences including fatality, destroyed

aircraft, and major injury) attributed to some degree to aircrew factors.12 These and similar

analyses have catalyzed tailored prevention strategies including CRM for commercial aviation,1

and “aircrew coordination training” (ACT) for Naval aviators.12

Study Design and Outcomes

Measures

Although the most obvious and meaningful measure of CRM effectiveness would appear

to be airline accident or “near miss” rates, these objective measures have not been used in

commercial aviation studies. Helmreich suggests that it is not possible to use these measures,

because accident rates are very low and “near misses” are voluntarily reported.10 Furthermore,

the content and structure of CRM training programs are variable.10

In response, researchers have developed tools that assess the effectiveness of CRM in

other ways. These tools include attitudinal surveys and peer performance rating questionnaires,

including the NASA/University of Texas Line/LOS Checklist (LINE/LOS Checklist),13 the

Cockpit Management Attitudes Questionnaire (CMAQ), and the Flight Management Attitudes

Questionnaire (FMAQ). The LINE/LOS Checklist is used to rate crew performance on critical

behaviors during specific segments of flight (eg, not rushing through briefing period, exhibiting

high levels of vigilance in both high and low workload conditions, etc). Ratings on each

behavioral element (ie, model for teamwork) range across 4 levels from poor to outstanding.

In contrast, CMAQ is used to evaluate the attitudes of crewmembers within and between

organizations, pre- and/or post-CRM training. Results are intended to serve as a proxy for

measuring crew process and performance.14 The instrument has been validated by comparing

self-reported attitudes with performance ratings made by experienced Check Airmen, experts

trained in peer evaluation.15 The FMAQ is a revised version of the CMAQ that was developed by

Helmreich and colleagues in response to attitudinal differences observed in flight crews from

different countries.16

Observation of crew performance in simulated flights has also been used.
503

Representative Studies

Several studies have utilized proxy tools to test the effectiveness of CRM.8,12,17 One study

by Helmreich and colleagues consisted of an assessment of the attitudes before versus after CRM

training (pre-test versus post-test).17 Crew behaviors were noted by a trained observer using the

NASA/University of Texas Line/LOS Checklist.18 More than 2000 line flights and LOFT

sessions were included in the analysis. Overall performance of crews was classified as “below

average,” “average,” or “above average” by Check Airmen and LOFT instructors.

As a result of the CRM training, the percentage of crews rated as “above average”

increased while the percent rated “below average” decreased. Performance ratings differed

between fleets and airlines. Superior pilots also shared many common attitudes, (for example,

they were aware of their personal limitations and diminished decision-making capacity during

emergencies). In addition, they encouraged crewmembers to question their decisions and actions,

were sensitive to the personal problems of other crewmembers, and recognized the need to

verbalize plans and to train other crewmembers.

A second study by Barker and colleagues compared the effectiveness of 17 CRM-trained

flight crews on military mission simulators, divided according to whether they were “fixed” or

“formed” crews.8

 Nine of the crews were defined as "fixed" since they had flown together for six

months or longer; the remaining 8 were “formed,” as they had flown together for less than 6

months. Each crew was asked to participate in a simulated mission. The first leg of the mission

was programmed to be problem-free, but the second leg required crews to address a safety issue.

As with the earlier study, crew behaviors were observed using the NASA/University of Texas

Line/LOS Checklist. Surprisingly, the formed crews committed fewer minor errors, but the

number of major errors did not differ significantly between the groups.8

 The authors concluded

that formed crews may experience less ineffective coordination than fixed crews, as the latter

might be more complacent from the routine of working together, but that further research was

needed.

A third study evaluated rates of naval aviation mishaps, and the role of CRM failures.12

While the study primarily compared crew performance in 2 types of equipment, the aircrew

performance deficits were also compared with those seen during an earlier time period, prior to

implementation of aircrew coordinating training (ACT) programs (the specific form of CRM

used). Analysis of data from the post-ACT implementation period across the fleet revealed that

70% of human error mishaps were connected with aircrew factors, and that 56% of these resulted

from at least one CRM failure. The authors noted that these percentages were similar to those

reported in a separate study prior to ACT implementation. Because of a lack of controls or

adjustments for potential confounders, no conclusions about effectiveness of the ACT program

can be drawn.12
504

Comparison to Medicine

Sexton and colleagues compared flight crews with operating room personnel on several

measures, including attitudes toward teamwork.19 The study included more than 30,000 cockpit

crew members (captains, first officers, and second officers) and 1033 operating room personnel

(attending surgeons, attending anesthesiologists, surgical residents, anesthesia residents, surgical

nurses, anesthesia nurses). Data from the crew members were obtained from previous

administrations of the CMAQ and FMAQ to major airlines around the world (over a 15-year

period). The operating room participants were mailed an analogous questionnaire (CMAQ

modified20), administered over a period of 3 years at 12 teaching and non-teaching hospitals in

the United States and abroad (Italy, Germany, Switzerland, and Israel).

The level of teamwork perceived by attending surgeons compared with other operating

room staff differed markedly. A majority of surgical residents (73%) and attending surgeons

(64%) reported high levels of teamwork, but only 39% of attending anesthesiologists, 28% of

surgical nurses, 25% of anesthesia nurses, and 10% of anesthesia residents reported high levels

of teamwork. A bare majority (55%) of attending surgeons rejected steep hierarchies (determined

by whether they thought junior team members should question the decisions of senior team

members). In contrast, 94% of airline crew members preferred flat hierarchies.

It was also noted that medical participants were far more likely to agree with the

statement “Even when fatigued, I perform effectively during critical times.” Seventy percent of

attending surgeons agreed with this statement, as well as 56% of surgical residents, 60% of

surgical nurses, 57% of anesthesia residents, 55% of anesthesia nurses, and 47% of attending

anesthesiologists. In contrast, 26% of pilots agreed with this statement.

Applications of CRM Principles in Medicine

The Sexton study and other analyses suggest that safety-related behaviors that have been

applied and studied extensively in the aviation industry may also be relevant in health care. We

identified CRM applications in several dynamic decision-making health care environments: the

operating room, labor and delivery, and the emergency room.3,21,22 In addition, Gaba has noted

that some other domains (eg, cardiac arrest response teams) that have active simulation training

are currently incorporating a broader range of CRM-like training methods.23 (Simulators are

covered in more detail in Chapter 45).

Practice Description

Crew Resource Management in Health Care Settings

As with aviation, the medical application of CRM has required tailoring of training

approaches to mirror the areas in which human factors contribute to mishaps. In anesthesiology

65-70% of safety problems (accidents or incidents) have been attributed at least in part to human

error. In response, several anesthesiologists from the VA Palo Alto Health Care System and

Stanford University, with funding from the Anesthesia Patient Safety Foundation, developed

Anesthesia Crisis Resource Management (ACRM), modeled on CRM.3,23 The original

demonstration courses consisted of didactic instruction, videotape of a reenactment of an

aviation disaster, videotape of an actual anesthetic mishap, simulation training and a debriefing

session. Ongoing courses include the use of a textbook that catalogues 83 critical events (eg,

acute hemorrhage, bronchospasm, seizures), and approaches to managing them.24 Currently,

there are 3 ACRM courses offering progressively more challenging material, a Working Group
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on Crisis Management Training in Health Care formed by the developers of ACRM that has

initiated formal ACRM instructor training, and thoughtful consideration of pragmatic approaches

to evaluating ACRM.23

Helmreich and Schaefer have also advanced CRM theory in the operating room

environment by adapting their model of team performance. This framework describes the team

performance inputs that are critical to essential team functions that in turn lead to desired

outcomes (defined as patient well-being). Examples of inputs include individual aptitudes,

physical environment, and culture (professional, organizational, and national). Performance

functions consist of team formation and management, surgical procedures, communications,

decision processes, and situational awareness.18

Another application of CRM to the health environment is the MedTeams behavior-based

teamwork system, developed by Dynamics Research Corporation, and sponsored by the Army

Research Laboratory. It aims to adapt research in team performance and training from military

helicopter aviation to emergency medicine.22,25,26 Thus far, specific applications have been

developed for Emergency Department care and labor and delivery units.27 The system is

implemented through courses and assessment tools. The Emergency Team Coordination Course

(ETCC) includes 5 team dimensions or goals (ie, maintain team structure and climate, facilitate

planning and problem-solving, enhance communication among team members, facilitate

workload management, improve team-building skills). Each goal is tied to specific teamwork

tasks. For example, tasks for the first goal (maintain team structure and climate) include

“establish team leader,” “form the team,” “set team goals,” and “assign roles and

responsibilities.”

22 Like the CRM approach to the “Error Troika,” the MedTeams approach is

based on avoiding errors, trapping them as they occur, and mitigating the consequences of actual

errors. Principles underlying the MedTeams approach include:

• Team responsibility for patients

• A belief in clinician fallibility

• Peer monitoring

• Team member awareness of patient status, team member status and

institutional resources

Peer monitoring is a fundamental component of the MedTeams system, as well as a

feature of the ACRM and aviation field’s CRM approaches. Along with his or her clinical

responsibilities, each team member undertakes the intermittent process of peer monitoring or

"check" actions, engaging in this check cycle as frequently as possible. The teamwork check

cycle begins with each team member monitoring his or her own situation awareness and crossmonitoring the actions of other teammates. If during the monitoring mode the monitoring

teammate observes a suspected error in progress, that individual intervenes with a direct question

or offer of information. The erring teammate may then acknowledge the lapse, correct it and

continue working. Alternatively, the monitoring teammate may have lost situation awareness.

The non-erring monitored colleague can then provide feedback to correct the peer's situation

awareness. If team members are in strong disagreement about how patient care should proceed,

advocacy, assertion and perhaps third-party involvement may be used to resolve the situation.

Over time, the check cycle becomes habitual, resulting in hundreds of team checks daily, all with

the potential to break the error chain.

Recently, ACRM has been extended to a full-day course on neonatal resuscitation

training for neonatologists and pediatricians.21 Called “NeoSim”, the course combines traditional
506

training methods with reviews of literature and didactic instruction with simulation. Debriefing

follows, using videotape of the simulation. As with the other examples, the emphasis of teaching

behavioral teamwork skills along with technical content is the hallmark of CRM interventions in

health care.

Evidence for Effectiveness of the Practice

The most thoroughly studied of the medical CRM applications is ACRM, although as

with the aviation examples, rigorous evaluations are challenging to design. Few studies utilize a

control group, although researchers have reported assessment methods for determining both

technical and behavioral performance from simulator videotapes28 (see also Chapter 45). A

before-after ACRM training analysis (Level 3 Study Design) of trainees’ knowledge-base (Level

3 Outcome) for crisis yielded mixed results.3

 The average score on the post-test was significantly

greater than the pre-test for one trainee class, composed mostly of residents. For the other class

of experienced anesthesiologists, the test scores did not change and were at the same level as the

post-test scores of class of residents. Subjective data evaluating the course indicated that trainees

“uniformly felt that the ACRM course was an intense, superior form of training related to an

important, but inadequately taught, component of anesthesia practice.”

3

 Another study of ACRM

at Harvard also found that participants rated the course favorably, with over 80% responding that

they felt the course should be taken every 24 months or less.29

As with aviation, the incremental value of this form of training is difficult to link to

improvements in teamwork performance and better safety records. At the time of this literature

assessment, there were no published data to describe the effects on medical error rates of the

MedTeams approach. The NeoSim course participants provided positive responses to openended questions about their satisfaction with the course.21

Costs and Implementation

Helmreich has noted some of the limitations associated with CRM.10 At this time, the

evidence connecting CRM approaches to improving patient safety does not exist,

notwithstanding the face validity of the approach. Nevertheless, a long history of variants of the

approach offers health care a reasonable foundation from which to draw practical and evidencedbased resources30 for further development and adaptation of CRM, as well as measurement

methods to ascertain its effectiveness.

At a minimum, implementation of the CRM approach in health care settings requires

customization of tools and techniques for each specific care venue, as is illustrated by

adaptations implemented thus far. This customization comes at considerable cost and cannot be

expected to immediately reap safety benefits. At the time of this review, approximate costs for

implementing the MedTeams system ranged from $15,000-$35,000, with additional costs for

ongoing activities (such as continuing education) that ranged from $8,000-$20,000 (R. Simon,

personal communication, April 2001). Similarly, marginal costs for CRM-like training based on

the ACRM experience are estimated at $800 to $2,000 per participant per day (D. M. Gaba,

personal communication, June 2001). These costs do not include the overhead of starting a

program (eg, simulator investment, training instructors), nor do they factor in the cost of reduced

practice work hours, if these are above those devoted to current training time.

Cultural shifts in medicine are also necessary if the CRM approach is truly to take root.

CRM applications are relatively novel in health care, a field in which professional training and

education have traditionally focused on developing technical proficiency rather than facilitating

human interaction. Although communication and decision making are central to medical
507

practice, relatively little about this topic has appeared in medical literature, despite the fact that

information flow is critical, particularly in high acuity venues such as the operating room and

emergency departments. Ideas must be elicited, debated and evaluated without discrimination

based on the status of the staff person offering the information.31

Paradoxically, the attachment to hierarchy may be the reason that a small percentage of

participants can be expected to reject CRM training. Research has shown that some resistance is

rooted in personality characteristics. Crew members lacking in achievement motivation and

interpersonal skills are more likely to reject the training. Additionally, CRM practices decay over

time, even with repeated training, requiring continuing expenditures to retain the hoped-for

gains.10

Comment

CRM has evolved in the airline industry for more than 20 years, and has been extensively

applied during the past decade. Although no definitive data link CRM to decreased aviation error

per se, the industry has accepted the face validity of the practice, and it is now an integral part of

training. Over time, survey data from thousands of civilian and military participants in the

United States and abroad has been accrued. These data indicate that most flight crew members

accept CRM training, and find it both relevant and useful.7

The studies reviewed provide some support for the notion that CRM is worth further

investigation in health care. However, it cannot yet be concluded that CRM is a practice that can

reduce medical errors. Additional research in this area is warranted, although measurement and

study design are particularly challenging. As noted, although the evidence from aviation, where

CRM is well-established, has shortcomings, data are easier to capture since CRM assessments

can be grafted onto mandatory, ongoing, yearly pilot assessments conducted both in simulators

and in real flights (D. M. Gaba, personal communication, June 2001). In medicine, where

ongoing assessments are not the norm, capturing relevant data will be more difficult logistically

and much more expensive than in aviation. Consequently, and for the analogous reasons that

aviation has adopted CRM based on face validity, health care decision makers may wish to

consider face validity in lieu of massive research investments.

Nonetheless, evaluations of CRM that focus on intermediate outcomes (eg, trainee

performance) are feasible, and instructive for optimizing components of CRM programs. CRM

design and evaluation resources are becoming more widely available,30 and health care should

continue to consult these sources, building on the advances made in other fields.

Acknowledgements

The authors are grateful to Robert Simon, Chief Scientist at Dynamics Research

Corporation, for providing details on the MedTeams approach.

References

1. Helmreich RL. On error management: lessons from aviation. BMJ. 2000; 320: 781-5.

2. Shortell SM, Zimmerman JE, Rousseau DM, Gillies RR, Wagner DP, Draper EA, et al.

The performance of intensive care units: does good management make a difference? Med

Care. 1994; 32: 508-25.

3. Howard SK, Gaba DM, Fish KJ, Yang G, Sarnquist FH. Anesthesia crisis resource

management training: teaching anesthesiologists to handle critical incidents. Aviat Space

Environ Med. 1992; 63: 763-70.
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4. Cooper GE, White MD, Lauber JK. Resource management on the flightdeck: proceedings

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5. Lauber JK. Cockpit resource management: background and overview. In: Orlady HW,

Foushee HC, eds. Cockpit resource management training: proceedings of the NASA/MAC

workshop. Moffett Field, Calif: NASA - Ames Research Center. NASA Conference

Publication No. 2455.

6. Wiener EL, Kanki BG, Helmreich RL. Cockpit resource management. San Diego, Calif:

Academic Press, Inc.; 1993.

7. Helmreich RL, Foushee HC. Why crew resource management? Empirical and theoretical

bases of human factors in training and aviation. In: Wiener E, Kanki BG, Helmreich RL,

eds. Cockpit resource management. San Diego, Calif: Academic Press; 1993: 3-45.

8. Barker JM, Clothier CC, Woody JR, McKinney EH, Jr., Brown JL. Crew resource

management: a simulator study comparing fixed versus formed aircrews. Aviat Space

Environ Med. 1996; 67: 3-7.

9. Helmreich RL, Merritt AC. Cultural issues in crew resource management. Conference

presentation at the ICAO Global Human Factors Seminar; April, 1996; Auckland, New

Zealand.

10. The evolution of crew resource management training in commercial aviation. Available at:

http://www.psy.utexas.edu/psy/helmreich/Evolution_IJAP_for_Dist.htm. Accessed June

18, 2001.

11. Billings CE, Reynard WD. Human factors in aircraft incidents: results of a 7-year study.

Aviat Space Environ Med. 1984; 55: 960-5.

12. Wiegmann DA, Shappell SA. Human error and crew resource management failures in

Naval aviation mishaps: a review of U.S. Naval Safety Center data, 1990-96. Aviat Space

Environ Med. 1999; 70: 1147-51.

13. Helmreich RL, Wilhelm JA, Kello JE, Taggart WR, Butler RE. Reinforcing and evaluating

crew resource management: Evaluator/LOS instructor reference manual. Austin, Tex:

NASA - University of Texas at Austin; 1990. Technical Manual 90-2.

14. Gregorich SE, Helmrich RL, Wilhelm JA. The structure of cockpit-management attitudes.

J Appl Psychol. 1990; 75: 682-90.

15. Helmreich RL, Foushee BR, Benson R, Russini W. Cockpit Resource Management:

Exploring the attitude-performance linkage. Aviat Space Environ Med. 1986; 57: 1198-200.

16. Helmreich RL, Merritt AC, Sherman PJ, Gregorich SE, Wiener EL. The flight management

attitudes questionnaire. Austin, Tex: NASA/University of Texas/FAA; 1993. Technical

Report 93-5.

17. Helmreich RL, Wilhelm JA, Gregorich SE, Chidester TR. Preliminary results from the

evaluation of cockpit resource management training: performance ratings of flight crews.

Aviat Space Environ Med. 1990; 61: 576-9.

18. Helmreich RL, Schaefer HG. Team performance in the operating room. In: Bogner MS, ed.

Human error in medicine. Hillside, NJ: Lawrence Erlbaum; 1998.

19. Sexton JB, Thomas EJ, Helmreich RL. Error, stress, and teamwork in medicine and

aviation: cross sectional surveys. BMJ. 2000; 320: 745-9.

20. Helmreich RL, Merritt AC. Culture at work in aviation and medicine: national,

organizational, and professional influences. Hants, England: Ashgate Publishing Limited;

1998.
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21. Halamek LP, Kaegi DM, Gaba DM, Sowb YA, Smith BC, Smith BE, et al. Time for a new

paradigm in pediatric medical education: teaching neonatal resuscitation in a simulated

delivery room environment. Pediatrics. 2000; 106: E45.

22. Risser DT, Rice MM, Salisbury ML, Simon R, Jay GD, Berns SD. The potential for

improved teamwork to reduce medical errors in the emergency department. The MedTeams

Research Consortium. Ann Emerg Med. 1999; 34: 373-83.

23. Gaba DM, Howard SK, Fish KJ, Yasser SA. Simulation-based training in Anesthesia Crisis

Resource Management (ACRM): a decade of experience. In: Simulation & Gaming. Vol

32: Sage Publications, Inc. In Press.

24. Gaba DM, Fish KJ, Howard SK. Crisis Management in Anesthesiology.: Churchill

Livingstone Inc.; 1994.

25. Small SD, Wuerz RC, Simon R, Shapiro N, Conn A, Setnik G. Demonstration of highfidelity simulation team training for emergency medicine. Acad Emerg Med. 1999; 6: 312-

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26. Dynamics Research Corporation. Training analysis and delivery. Available at:

http://www.drc.com/TrainingAnalysis/medteams.htm. Accessed June, 2001.

27. Spath PL, ed. Error reduction in health care: a systems approach to improving patient

safety. San Francisco, Calif: Jossey-Bass Publishers; 1999.

28. Gaba DM, Howard SK, Flanagan B, Smith BE, Fish KJ, Botney R. Assessment of clinical

performance during simulated crises using both technical and behavioral ratings.

Anesthesiology. 1998; 89: 8-18.

29. Holzman RS, Cooper JB, Gaba DM, Philip JH, Small SD, Feinstein D. Anesthesia crisis

resource management: real-life simulation training in operating room crises. J Clin Anesth.

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30. Salas E, Rhodenizer L, Bowers CA. The design and delivery of crew resource management

training: exploiting available resources. Hum Factors. 2000; 42: 490-511.

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departments. Acad Emerg Med. 2000; 7: 1204-22.
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Chapter 45. Simulator-Based Training and Patient Safety

Ashish K. Jha, MD

University of California, San Francisco School of Medicine

Bradford W. Duncan, MD

Stanford University School of Medicine

David W. Bates, MD, MSc

Harvard Medical School

Background

For a number of years, simulators have been used in aviation, nuclear power, military

flight operations and other industries as a training tool and method to assess performance. Their

use is nearly universal in high reliability organizations.1

 Recently the use of simulation in

medicine has increased markedly, in part due to greater awareness of the importance of patient

safety.

Defined broadly, a simulator replicates a task environment with sufficient realism to

serve a desired purpose.1

 In medical training, simulators can substitute for actual patients and can

be as simple as utilizing pigs’ feet to practice suturing, or as complex as virtual reality machines

and re-creations of actual clinical environments for surgeons, radiologists and anesthesiologists.

In a general sense, they improve patient safety by allowing physicians to become better trained

without putting patients at risk. For example, in a randomized controlled trial, Peugnet and

colleagues used a virtual reality simulator to train physicians to perform retinal photocoagulation

and found that surgeons who trained with the simulator performed the procedure as well as those

who trained with patients.2

 Gaba lists several other advantages of simulation, among them3:

• Presentation of uncommon but critical scenarios in which a rapid response is

needed (eg, malignant hyperthermia, which occurs once in every 40,000

anesthesia cases).4

 To conduct systematic training about managing such

critical events there is little alternative but to use simulation.

• Errors can be allowed to occur and reach their conclusion—in real life a more

capable clinician would have to intervene—so participants can see the results

of their decisions and actions.

• With mannequin-based simulators clinicians can use actual medical

equipment, exposing limitations in the human-machine interface.

• Complete interpersonal interactions with other clinical staff can be explored

and training in teamwork, leadership, and communication provided. In a

number of medical fields, simulation has been used in crew resource

management (CRM) training1

 (see Chapter 44), where the focus is on

behavioral skills such as inter-team communication during critical incidents.

Human error is a leading cause of adverse anesthesia events that lead to poor patient

outcomes5

 and may play an important role in surgical errors as well.6 However, it may be

difficult to demonstrate improved patient outcomes from simulation because adverse events are

unusual and there are an extreme number of potential confounders. Given these difficulties,

performance has been used as a surrogate outcome, despite concerns that it may be a less than

perfect measure. It is yet unclear which attributes of performance matter most to patient

outcomes. Additionally, the methods (eg, reliability and consistency) and timing (eg, duration of
512

follow-up) by which performance is measured also remain ill-defined.1

 Studies of the

effectiveness of simulators often are limited in that they measure performance using the same

training simulator, which may favor those who have trained on the simulator itself. In other

words, seemingly improved performance may not translate to actual patient care. Of the studies

that have extended laboratory simulation to patient care, few have evaluated the impact on

medical error or established a clear link between simulator training and patient outcomes.

This chapter reviews the evidence regarding the use of simulators in the training and

ongoing education of health care providers as a patient safety measure. Not included in this

review is the use of simulators in the planning or preparation of diagnostic or therapeutic

interventions in specific patients (eg, calculation of radiotherapy doses using computer

simulations, planning a surgical procedure for a specific patient using 3-D simulations based on

the anatomical data from the actual patient). While these kinds of simulation clearly decrease the

morbidity and mortality associated with their particular procedures, they are omitted here

because they focus on unique characteristics of individual patients that may not be generalizable

to other patients. Other uses of simulators beyond the scope of this discussion include simulators

to measure worker proficiency,7-10 to identify areas for educational intervention, and to target

improvements in training.11,12

Simulators in Anesthesia

Patient simulators have been most widely studied in anesthesia where human error may

account for over 80% of critical incidents.5

 Simulators range from simple mannequins to highfidelity simulators that recreate the operating room experience. According to one study, 71% of

medical schools in Canada, the United Kingdom and other western nations used mannequins or

some other form of simulator to teach anesthesia to medical students.13 There is a growing body

of literature on the different roles that simulators can play in anesthesia training.14

Studies have found that simulators can effectively identify errors and appropriateness of

decision making in anesthesia. For example, during 19 comprehensive anesthesia simulations,

DeAnda et al documented 132 unplanned incidents, of which 87 (66%) were due to human error

and 32 (27%) were considered critical incidents.15 Schwid and O’Donnell have also used

simulators to document the type of errors that anesthesiologists make in critical incidents,

finding errors in monitor usage (37%), airway management (17%), ventilator management

(13%), and drug administration (10%).16 Gaba and colleagues studied both the appropriateness

of decisions and response time of anesthesia trainees to simulated critical incidents.8

 They found

great individual variability as well as variability by incident in the accuracy and timeliness of

response. Some simulated incidents, such as cardiac arrest, had major errors in management a

majority of the time. Based on these studies, patient simulators can be used to identify areas for

further education or training of anesthesia providers.

We identified 2 studies of the effect of simulators on anesthetists’ performance. Schwid

and colleagues studied the impact of a computer screen-based anesthesia simulator in a

randomized, controlled trial of 31 first-year anesthesia residents.17 Residents that had trained on

the simulator with individualized debriefing responded better to critical events on a mannequinbased simulator than those who received standard training without the simulator. Using a

randomized, controlled design, Chopra and colleagues studied management of simulated critical

situations by 28 resident or staff anesthesiologists.18 The performance of subjects who trained on

the simulator was superior to that of subjects who did not receive that training.

Another setting where simulators may play an important role is in crew resource

management (CRM). Though establishing the effectiveness of simulation in CRM training may
513

be difficult,19 initial work has been done on reliably and consistently rating performance.10 CRM

is discussed further in Chapter 44.

Proficiency on a simulator does not ensure proficiency in clinical settings. Simulator

fidelity (ie, how accurately the simulator replicates reality) is imperfect. It is much more difficult

to “re-create” a human being than to do so for, say, an airplane. This limitation is illustrated by a

study conducted by Sayre and colleagues. They studied emergency medical technicians (EMT)

who learned intubation techniques on anesthesia mannequins.20 After successfully intubating the

mannequins 10 times, they were permitted to intubate patients in the field, where their

proficiency was only 53%. Other factors can inhibit optimum learning using simulation or the

applicability of learning to real practice. Some participants may be more vigilant than usual

during simulator sessions. Others may be unable to “suspend disbelief,” may treat the simulation

only as a game, or act in a cavalier fashion, knowing that the simulator is not a real patient.21

Refinement of simulators to make them more sophisticated and life-like may help to improve the

quality of the training that simulators can provide. Appropriate construction of curricula and

debriefings can also minimize the potential problems of simulation training.

Simulators in Radiology

The number of radiologic examinations that require sedation, analgesia, or contrast media

has increased rapidly in recent years.22 Despite their rarity, serious medication reactions do occur

and require prompt, appropriate management. Some evidence of suboptimal management23 has

prompted the creation of computer-based simulators to improve training in these areas.24

Simulators have also been used to measure the effectiveness of strategies to teach trainees about

critical incidents, but studies have not reported the effectiveness of simulators as adjuncts to

training. Sica and colleagues developed a computer-based simulator that was used to study the

effectiveness of a lecture and videotape-based intervention on critical incidents for radiology

housestaff.25 Those residents who underwent the intervention scored better on the simulator than

those that had only received basic, standard training. The authors concluded that the simulator

was an effective way of assessing the utility of the educational course.

Simulators in Surgery

As surgical technique and expertise has changed drastically over recent decades, some

methods used to train surgeons have evolved as well. Simulators in the surgical setting are aimed

at improving surgeons’ technical skills and dexterity. Training on simulators and virtual reality

machines, though still in its nascent stages, is becoming increasingly accepted.26,27 Surgical

simulators have been developed for a variety of procedures: endovascular repair of abdominal

aortic aneurysms,28 sinus surgery29,30 gynecologic surgery,31 orthopedic surgery,32 prostatic

surgery,33 amniocentesis procedures,34 and oral surgery.35 Nonetheless, many of these have yet to

be formally evaluated in terms of efficacy in improving physician performance in patient care.

We identified several studies that evaluated physician performance after training on a

surgical simulator. Derossis evaluated surgical residents and attendings in a randomized study

and found that those trained with a simulator had greater proficiency in suturing, transferring,

and mesh placement, when tested on the simulator, than did the control group.36 They

subsequently found that when tested in vivo in pigs, surgeons (both attendings and residents)

who had been randomized to the simulator arm were more proficient at the same skills.37 Scott

and colleagues studied the impact of a video-trainer on laparoscopic cholecystectomy skills.38

They randomized surgical residents to training on a video-trainer versus no formal training over
514

a 30-day period. At the end of the period, when tested on pre-specified tasks on the video trainer,

those who trained on the video trainer did uniformly better.

Intuitively, improved technical skills should lead to fewer complications during surgery.

Wallwiener and colleagues developed a surgical trainer that, when used in conjunction with

other improvements in their training program, led to lower rates of hysteroscopic

complications.39,40 However, for most simulators the link between improvements in technical

skills and dexterity from simulator training and prevention of adverse events has yet to be

established and deserves formal investigation. Further, problem-based surgical simulation (eg,

avoiding inadvertent ligation of the ureter during hysterectomy) may improve patient safety not

only by improving skills, but also by training surgeons to better anticipate and avoid

complications and to manage them should they occur.

Simulators in Gastroenterology

Simulators have been developed to train physicians in the technical skills required in

endoscopy.41-43 We identified one study that evaluated the effect of simulator training on

physician performance. In a small randomized controlled trial enrolling 10 residents, Tuggy and

colleagues found residents who trained for flexible sigmoidoscopy using a virtual reality

simulator were faster, visualized a greater portion of the colon, and made fewer directional errors

in actual patients.44

Simulators in Cardiology

Cardiology training has long used a variety of simulators from audiocassettes of heart

tones to full patient simulators. Two simulators have been evaluated. Champagne and colleagues

demonstrated that a heart sound simulator could increase medical students’ recognition of

pathologic heart sounds.45 Ewy and colleagues studied the efficacy of “Harvey,” a cardiology

patient simulator.46 In a study enrolling 208 senior medical students at 5 medical schools,

participants were randomized to receive training on Harvey versus a standard cardiology

curriculum during their cardiology elective. Students who had been trained with Harvey

performed skills better both when tested with the simulator and when tested with real patients.

Some physicians have expressed concern that training on simulators may decrease

professionalism. In this study, there was no difference in the way patients perceived the

professionalism of the students trained on Harvey compared with students who received standard

training.

Systems that simulate the cardiovascular anatomy and physiology have also been

developed. Swanson and colleagues created a cardiovascular simulator to train physicians on the

workings of mechanical valves and balloon assist devices, and to recognized diseased vessels.47

As cardiac procedures have become more invasive, simulators to train cardiologist in these

procedures have become more common,48, 49 but their effect on resident performance has not

been evaluated formally.

Comment

Although simulators have been used for many years in a variety of settings, data on their

efficacy are still emerging. While there is currently no evidence that simulation-based training

leads to improved patient outcome, it may prove difficult to conduct such studies. These would

require large cohorts of patients to be followed during and after care by clinicians who were

randomized to have undergone different cumulative amounts of simulation training. Because

adverse events are uncommon, and there are a large number of patient-based and system-based
515

factors that contribute to negative outcomes, any such study would have to be massive and

prolonged. Instead, provider performance, with its known limitations, has been and will continue

to be used as a surrogate outcome. Nonetheless, as Gaba has asserted “...no industry in which

human lives depend on skilled performance has waited for unequivocal proof of the benefits of

simulation before embracing it.”

50 Certain benefits are clear. In training for procedures,

simulators have high face validity because they ease trainees’ transition to actual patients, which

seems inherently beneficial as a means to avoid adverse events. Further, procedural success is

related to the experience of the operator, known as the volume-outcome relationship51, 52 (see

Chapter 19). As simulators become more advanced, they may be reasonable substitutes to

improve proficiency of both trainees and low volume physician operators. This increase in

proficiency may have an important impact in patient outcomes. Future studies of the link

between simulator-based training and performance on actual patients will improve our ability to

better assess the appropriate role of simulators in training and patient safety.

The costs of simulators vary widely and need to be considered. “Home-made” or simple

trainers are far less expensive than complex simulators or full-scale simulation centers. The

average cost of high-fidelity patient simulators is on the order of $200,000. Medium fidelity

simulators may be as little as $25,000. Establishing a dedicated simulation center can cost up to

$1,000,000 (including the simulator) depending on the amount of space, the type of clinical

equipment to be used, the extent of renovations needed, and the sophistication of the audiovisual equipment. However, such capital costs are amortized over a long period of time, and such

centers typically are used for a wide variety of training curricula for diverse target populations.

Further, for most simulation training the dominant cost is that of instructor time. Another indirect

cost is that of removing clinical personnel from revenue producing work to undergo training.

The health care industry currently does not fully embed time or costs of training into the system,

but instead often leaves these costs for the individual clinicians to bear.

There are potential risks to simulation-based training. Where the simulator cannot

properly replicate the tasks or task environment of caring for patients, there is a risk that

clinicians might acquire inappropriate behaviors (negative training) or develop a false sense of

security in their skills that could theoretically lead to harm. Although there are no data to suggest

that this currently happens, such risks will have to be weighed and evaluated as simulators

become more commonly used.

In summary, although there is currently little evidence that simulation training improves

patient care, the experience with simulation in other industries and the high face validity of their

applications in health care has led many institutions to adopt the technology. It is likely that

simulators will continue to be used and their role in training of medical personnel will grow.

Definitive experiments to improve our understanding of their effects on training will allow them

to be used more intelligently to improve provider performance, reduce errors and ultimately,

promote patient safety. Although such experiments will be difficult and costly, they may be

justified to determine how this technology can best be applied.

References

1. Bushell E, Gaba, D.M. Anesthesia Simulation and Patient Safety. Problems in Anesthesia.

2001;In Press.

2. Peugnet F, Dubois P, Rouland JF. Virtual reality versus conventional training in retinal

photocoagulation: a first clinical assessment. Comput Aided Surg. 1998;3:20-26.

3. Gaba DM, DeAnda A. A comprehensive anesthesia simulation environment: re-creating

the operating room for research and training. Anesthesiology. 1988;69:387-394.
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4. Dunn D. Malignant hyperthermia. AORN J. 1997;65:728,731,passim.

5. Cooper JB, Newbower RS, Long CD, McPeek B. Preventable anesthesia mishaps: a study

of human factors. Anesthesiology. 1978;49:399-406.

6. Spencer FC. Human error in hospitals and industrial accidents: current concepts. J Am Coll

Surg. 2000;191:410-418.

7. Keyser EJ, Derossis AM, Antoniuk M, Sigman HH, Fried GM. A simplified simulator for

the training and evaluation of laparoscopic skills. Surg Endosc. 2000;14:149-153.

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Anesth Analg. 1989;68:444-451.

9. Gaba DM. Anaesthesia simulators. Can J Anaesth. 1995;42(10):952-953.

10. Gaba DM, Howard SK, Flanagan B, Smith BE, Fish KJ, Botney R. Assessment of clinical

performance during simulated crises using both technical and behavioral ratings.

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11. Ruppert M, Reith MW, Widmann JH, et al. Checking for breathing: evaluation of the

diagnostic capability of emergency medical services personnel, physicians, medical

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Med. 2000;7(10):1077-1082.

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answer? Biomed Instrum Technol. 1996;30:341-345.

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Anesth Analg. 1990;71:77-82.

16. Schwid HA, O'Donnell D. Anesthesiologists' management of simulated critical incidents.

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17. Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation

with debriefing improves performance in a mannequin-based anesthesia simulator. Teach

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Gaming. 2001;32(2):175-193.

20. Sayre MR, Sakles JC, Mistler AF, Evans JL, Kramer AT, Pancioli AM. Field trial of

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25. Sica GT, Barron DM, Blum R, Frenna TH, Raemer DB. Computerized realistic simulation:

a teaching module for crisis management in radiology. AJR Am J Roentgenol.

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Coll Surg. 1996;81:77.

27. Ota D, Loftin B, Saito T, Lea R, Keller J. Virtual reality in surgical education. Comput Biol

Med. 1995;25:127-137.

28. Chong CK, How TV, Black RA, Shortland AP, Harris PL. Development of a simulator for

endovascular repair of abdominal aortic aneurysms. Ann Biomed Eng. 1998;26:798-802.

29. Rudman DT, Stredney D, Sessanna D, et al. Functional endoscopic sinus surgery training

simulator. Laryngoscope. 1998;108(11 Pt 1):1643-1647.

30. Ecke U, Klimek L, Muller W, Ziegler R, Mann W. Virtual reality: preparation and

execution of sinus surgery. Comput Aided Surg. 1998;3:45-50.

31. Szekely G, Bajka M, Brechbuhler C, et al. Virtual reality based surgery simulation for

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32. Poss R, Mabrey JD, Gillogly SD, et al. Development of a virtual reality arthroscopic knee

simulator. J Bone Joint Surg Am. 2000;82-A(10):1495-1499.

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computer generated interactive transurethral prostatic resection simulator. J Urol.

1999;162:1633-1635.

34. Maher JE, Kleinman GE, Lile W, Tolaymat L, Steele D, Bernard J. The construction and

utility of an amniocentesis trainer. Am J Obstet Gynecol. 1998;179:1225-1227.

35. Bettega G, Payan Y, Mollard B, Boyer A, Raphael B, Lavallee S. A simulator for

maxillofacial surgery integrating 3D cephalometry and orthodontia. Comput Aided Surg.

2000;5:156-165.

36. Derossis AM, Bothwell J, Sigman HH, Fried GM. The effect of practice on performance in

a laparoscopic simulator. Surg Endosc. 1998;12:1117-1120.

37. Fried GM, Derossis AM, Bothwell J, Sigman HH. Comparison of laparoscopic

performance in vivo with performance measured in a laparoscopic simulator. Surg Endosc.

1999;13:1077-1081; discussion 1082.

38. Scott DJ, Bergen PC, Rege RV, et al. Laparoscopic training on bench models: better and

more cost effective than operating room experience? J Am Coll Surg. 2000;191:272-283.

39. Wallwiener D, Rimbach S, Bastert G. The HysteroTrainer, a simulator for diagnostic and

operative hysteroscopy. J Am Assoc Gynecol Laparosc. 1994;2:61-63.

40. Wallwiener D, Rimbach S, Aydeniz B, Pollmann D, Bastert G. Operative Hysteroscopy:

Results, Security Aspects, In Vitro Simulation Training (Hysterotrainer). J Am Assoc

Gynecol Laparosc. 1994;1(4, Part 2):S39.

41. Williams CB, Saunders BP, Bladen JS. Development of colonoscopy teaching simulation.

Endoscopy. 2000;32:901-905.

42. Aabakken L, Adamsen S, Kruse A. Performance of a colonoscopy simulator: experience

from a hands-on endoscopy course. Endoscopy. 2000;32:911-913.

43. Neumann M, Mayer G, Ell C, et al. The Erlangen Endo-Trainer: life-like simulation for

diagnostic and interventional endoscopic retrograde cholangiography. Endoscopy.

2000;32(11):906-910.

44. Tuggy ML. Virtual reality flexible sigmoidoscopy simulator training: impact on resident

performance. J Am Board Fam Pract. 1998;11:426-433.
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cardiac auscultation. Focus Crit Care. 1989;16:448-456.

46. Ewy GA, Felner JM, Juul D, Mayer JW, Sajid AW, Waugh RA. Test of a cardiology

patient simulator with students in fourth-year electives. J Med Educ. 1987;62:738-743.

47. Swanson WM, Clark RE. A simple cardiovascular system simulator: design and

performance. J Bioeng. 1977;1:135-145.

48. Wang Y, Chui C, Lim H, Cai Y, Mak K. Real-time interactive simulator for percutaneous

coronary revascularization procedures. Comput Aided Surg. 1998;3:211-227.

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simulator for interventional cardiology training. Catheter Cardiovasc Interv. 2000;51:522-

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1992;76:491-494.

51. Jollis JG, Romano PS. Volume-outcome relationship in acute myocardial infarction: the

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52. Jollis JG, Peterson ED, Nelson CL, et al. Relationship between physician and hospital

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Chapter 46. Fatigue, Sleepiness, and Medical Errors

Ashish K. Jha, MD

University of California, San Francisco School of Medicine

Bradford W. Duncan, MD

Stanford University School of Medicine

David W. Bates, MD, MSc

Harvard Medical School

Introduction

Fatigue may contribute to the human error component of medical errors.1-3 Hospitals

function around the clock, which necessitates shift work for many personnel. Physicians,

especially those in training, typically work long hours and are often sleep deprived.4

 Personnel

who work during evenings and at night experience disruptions in circadian rhythms, which may

aggravate fatigue. Although little research has focused specifically on fatigue in hospital

personnel and its relationship to medical error, studies outside the medical field demonstrate the

intuitive link between fatigue and degradation in performance and suggest some safety practices

that may be adopted in medicine. Although both acute and chronic fatigue may have detrimental

effects on the health of medical practitioners,5-7 this chapter focuses on fatigue’s direct effects on

patient safety. We review the literature on problem sleepiness among medical personnel, its

impact on performance, and interventions to address sleep deprivation: limiting work hours,

changes in shift scheduling, napping, and pharmaceutical aids. Although beyond the scope of

this chapter, factors that contribute to fatigue beyond sleepiness, such as job stress and work

load, should be considered as part of a multifaceted strategy to combat fatigue.

Background

Fatigue and sleepiness may affect patient safety in several ways. Physicians and nurses

need good attention, sound judgment, and often quick reaction time, especially in emergency

situations. Whether evaluating an electrocardiogram for signs of myocardial ischemia or

monitoring a patient during general anesthesia, degradation of attention, memory, or

coordination may affect performance and lead to adverse events. Research suggests that sleep

requirements and patterns are idiosyncratic, with wide variation across populations. In order to

design interventions that will effectively decrease or prevent these events, it is important to

understand the signs, prevalence, and impact of sleep deprivation and problem sleepiness.

Sleep Deprivation

Individuals differ in their optimal sleep requirements. Most sleep experts agree that

adults typically need between 6 and 10 hours of sleep per 24-hour period, with most people

requiring approximately 8 hours of sleep per day.8,9 When adults get less than 5 hours of sleep

over a 24-hour period, peak mental abilities begin to decline.2

 For short periods of time (2-3

days), adult who get 4 hours of sleep can function reasonably well, but below peak levels.2

However, even with sleep deprivation of just a couple of days, slower response times and

decreased initiatives are observed.10 After one night of missed sleep, cognitive performance may

decrease 25% from baseline.11,12 After the second night of missed sleep, cognitive performance

can fall to nearly 40% of baseline.12

With ongoing sleep deprivation (getting 2 to 3 hours less sleep than optimal), people

develop a sleep debt.

2

 If the sleep debt continues over 5 to 10 days, they are rarely maximally
520

alert and at some point general performance, and particularly cognitive performance, become

verifiably worse. Sleep debt also leads to slower response times, altered mood and motivation,

and reduced morale and initiative. A meta-analysis of the effect of sleep deprivation on

performance by Pilcher et al found that humans who are chronically sleep deprived function at

the 9th percentile of non-sleep-deprived subjects. Further, sleep deprivation affected mood more

than it did cognitive function; both were more affected than motor function.9

Night-Shifts and Shift Rotation

Shift work usually refers to a schedule in which some employees begin work at times

other than the morning. In hospitals, up to 35% of nurses may be required to work at times other

than the day shift.13 A report by the Association of Professional Sleep Societies concluded that

night-time operators’ fatigue contributed to 4 well known disasters: Exxon Valdez, Bhopal,

Chernobyl, and Three Mile Island.14 Fatigue has also been implicated in aircraft accidents15 and

in poor driving and accidents among truck drivers.16 It is well documented that shift workers

have disturbances in their circadian rhythm, as measured by changes in their melatonin and

cortisol levels.17 Sleep after night work tends to be shorter than sleep after day work, leading to

greater cumulative sleep deprivation.18-20 Shift workers have poorer quality of sleep, marked by

less REM sleep, and are less likely to feel refreshed after awaking. Between 60 and 70 percent of

shift workers complain of sleeping difficulties or problem sleepiness.21 Several surveys of shift

workers have found that those who work during night shifts are more likely to report sleepiness

at work.18,19,22,23 Alertness on the job is also affected, with employees showing less alertness

during nighttime shifts.24 In addition, shift workers tend to perform less well on reasoning and

non-stimulating tasks than non-shift workers.22,23

Prevalence and Severity

Fatigue and sleep deprivation are common among medical personnel. Long work-hours

are a tradition during residency,25 with most interns and residents working 80 to 100 hours a

week, often 36 hours at a time.26 During these shifts their sleep is limited, and is usually

interrupted.27 In a 1991 national survey, second-year residents reported an average of 37.6 hours

as the largest number of hours without sleep during their first postgraduate year and roughly

25% of the residents reported being on call in the hospital over 80 hours per week.26 A

movement in the late 1980s, prompted partly by the death of a young woman,28 led to regulations

in New York State dictating that residents could work a maximum of 80 hours per week, with a

maximum of 24 consecutive hours of patient care, and a minimum of 8 hours off duty between

shifts (see also chapter 55).29 Despite these regulations, unannounced inspections of 12 teaching

hospitals in New York State in March 1998 found 37% of all residents worked more than 85

hours per week, 20% of all residents and 60% of surgical residents worked more than 95 hours

per week, and 38% of all residents and 67% of all surgical residents worked more than 24

consecutive hours.30 In 2000, 8% of programs and institutions reviewed by the Accreditation

Council for Graduate Medical Education were cited as being in violation of their work-hour

requirements.31 Work-hour violations were noted in general surgery (35%), pediatrics (16%),

internal medicine (10%) and other training programs as well.31

Long hours and sleep deprivation continue after residency. Health care providers,

particularly those still in training or who have recently completed training, occasionally work

extra shifts to increase their income (“moonlighting”). One recent survey found that nearly half

of all emergency medicine residents moonlight.32 As many as 65% of internal medicine residents

and fellows moonlight33 and moonlighting is common among other residencies and
521

fellowships.34, 35 These shifts are often at odd hours, and therefore are disruptive to normal sleep

patterns. Among surgical staff, fatigue is common, especially since surgical teams can be

involved in long, complicated operative cases that can take 12 to 20 hours at a time.36,37

Multiple studies have documented the impact of fatigue on medical personnel

performance.38 However, these studies have been limited by poor study designs or outcomes that

may not correlate well with medical error. One study of nursing fatigue suggests that it may play

a role in increased error. Gold and colleagues administered a questionnaire to nurses at a large

academic hospital and found that nurses who worked a rotating schedule, when compared with

nurses who predominantly worked day shifts, were more likely to fall asleep at work and get less

sleep over all, and were nearly twice as likely to report committing a medication error.39

Using standardized testing, investigators have found that after a night of call, sleep

deprived physicians may have worse language and numeric skills,40 retention of information,41

short-term memory,42 and concentration.43 Performance on standardized tests may not reflect

performance in medical situations. Taffinder et al studied the impact of sleep deprivation on

surgical residents previously trained on a simulator and found that after a night without sleep,

surgeons were slower and more prone to errors on the simulator than those who had a normal

night of sleep.44 Similarly, Denisco et al studied anesthesia residents after a night of sleep

deprivation and found that those who had been on call and were sleep deprived scored less well

on simulated critical events.45 Smith-Coggins et al compared cognitive and motor performance

of emergency physicians and found that, as the 24-hour study period progressed, physicians were

more likely to make errors during a simulated triage test and while intubating a mannequin.19

However, other studies have failed to find an effect of sleep deprivation on cognitive

performance by resident physicians.46-48 Simulators may not reflect actual medical performance

(see chapter 45). Though psychomotor performance seems to be affected by sleep deprivation,

data are inconsistent as to fatigue’s impact on cognitive function and there are inadequate data

assessing its impact on clinical performance.

Few studies have looked at the impact of fatigue in hospital personnel on adverse events.

A retrospective study by Haynes et al of 6371 surgical cases, found that the risk of postoperative

complications among patients undergoing surgery was not increased when the surgical resident

was sleep deprived.49 These results may not be surprising for several reasons. First, the authors

did not measure the residents’ error rate, which may have been higher with sleep deprivation.

Second, the study did not measure the role attending physicians or other operating room

personnel may have played in averting adverse events when residents erred. The supervisory

aspect of system design can (and should) reduce both the frequency of individual mistakes (error

prevention) and the likelihood of adverse events given that errors are inevitable (error

absorption).1

 Finally, the rate of adverse events, including those that did not result in operative

complications (“near misses”), may have been higher but under reported. Well-designed studies

that evaluate the effects of fatigue among medical personnel on rates of medical errors or adverse

events would be useful. In the meantime, the lack of convincing data linking fatigue with poor

patient outcomes should not deter us from tackling the issue of fatigue among medical personnel.

Practice Descriptions

Hours of Service

We reviewed the evidence for 2 potential safety practices concerning hours of service: 8-

hour versus 12-hour length shifts and regulations limiting maximum shift length and/or total

hours worked. Most observational studies on optimal shift length to reduce fatigue and maximize
522

performance are in non-medical settings and present inconsistent findings. In a study of workplace accidents in Germany, Hanecke et al found accident risk increased exponentially after the

9th hour at work and was highest among workers whose shift began in the evening or night.50 The

authors concluded that shifts that last longer than 8 hours might lead to more worker fatigue and

higher risk of accidents. Axelsson and colleagues studied workers at a power plant and found no

difference in sleepiness or performance between those who worked 8-hour shifts and those who

worked 12-hour shifts.51 Another group found that switching from 8- to 12-hour shifts led to

increased alertness on the job and improved recovery time after night shifts.52 Overland has

proposed that work that requires complex cognitive tasks may be ill suited for longer shifts,

whereas work with limited cognitive demands may be well suited for longer shifts.53 Because the

components of work vary dramatically within and across industries, shift durations that maintain

performance in one setting may be ineffective in another.

We identified 9 observational studies comparing 8- versus 12-hour shifts for medical

personnel. Two studies of nursing care on 10 wards found that quantity54 and quality55 of care

were significantly lower with 12-hour shifts. Six studies of nurses56-61 and one of physicians62

measured outcomes including self-reported alertness, self-reported performance, and/or worker

satisfaction. While 2 nurse studies found that self-reported alertness, performance, and

satisfaction wane with longer shifts,56,57 Urgovics and Wright found that ICU nurses reported

higher job satisfaction and subjectively improved clinical performance with 12-hour shifts.60 The

3 remaining studies in nurses found no difference in either satisfaction or self-reported

performance between 8- and 12-hour shifts.58,59,61 A survey of emergency department physicians

found that those who worked 12-hour shifts were less likely to be satisfied than those who

worked 8-hour shifts.62 The relationship between these subjective outcomes measures and

medical error is not clear.

Hours of service regulations as an effort to reduce errors due to fatigue are standard in

some non-medical fields. Truck drivers are typically allowed to work no more than 10 hours at a

time and no more than 60 hours in one week. Airline pilots and air traffic controllers work

regulated hours and some data suggest waning performance as work-hours increase.24,63-65

Although most health care personnel are not subject to work-hour standards, many physiciansin-training are, either by statutory regulations or by being in an accredited training program. In a

retrospective cohort study, Laine and colleagues found the aforementioned New York State

regulations limiting resident work-hours had no effect on patient outcomes such as mortality or

transfers to the intensive care unit but were associated with increased rates of medical

complications and delays in diagnostic tests.66 These negative effects may have been related to

discontinuity of care and/or fewer physician-hours per patient. As the authors noted, “better care

may be provided by a tired physician who is familiar with the patient than by a rested physician

who is less familiar with the patient.”

66 In a case-control study, Petersen and colleagues found

that when patients were cared for by a physician other than their primary resident, they were 6

times as likely to suffer a preventable adverse event.67 Thus, fewer physician work hours may

lead to more physician discontinuity and potentially, more adverse events and poorer outcomes

for patients.

On the other hand, Gottlieb studied changes in a medical service staffing schedule that

allowed for reduced sleep deprivation, improved distribution of admissions throughout the week,

and improved continuity of inpatient care.68 After these changes were instituted, patients had

shorter lengths of stay, fewer ancillary tests, and fewer medication errors. Although it is difficult

to ascribe the improvements to changes in work-hours because several other changes were made

as well, it does appear that changes in work-hours can be made without adversely affecting
523

patient outcomes. Any effort to change duty hours for health care personnel in an effort to reduce

fatigue should factor in and continuously monitor numerous variables, including the potential

costs of discontinuity, medical complications and unnecessary hospital days, to ensure that the

measures do not compromise patient care. The costs needed to maintain adequate staffing in face

of lost physician work-hours has been estimated to be $360 million in New York State alone.69

However, the difficult task of estimating other costs and potential savings from implementing

these regulations has not been accomplished.

Finally, some authors have expressed concern that restriction of resident physician workhours may lead to poorer quality training and decreased professionalism among doctors.70 They

argue that restricted working hours will decrease a sense of obligation to patients and will

sanction self-interest over the well-being of patients. However, there are no data to substantiate

these concerns.

Direction and Speed of Rotation of Shift Work

The direction of shift rotation may impact worker fatigue. For workers who change from

one shift to another, a forward rotation of shift work (morning shifts followed by evening shifts

followed by night shifts) may lead to less fatigue on the job than backward rotation (day shift to

night shift to evening shift).71-74 Forward rotation appears easier to tolerate physiologically since

the natural circadian rhythm tends to move forward and it is more difficult to fall asleep earlier

than the normal bedtime. Several studies in non-medical personnel have shown that forward

rotation allows for better acclimation of the circadian rhythm.2,12,75 However, 2 other studies

found no significant difference in forward versus backward shift rotation.76,77 None of these

studies measured worker performance or error rates and we found no studies that evaluated

direction of shift work rotation among medical personnel.

Another variable in scheduling is the speed of shift work rotation. Studies suggest that

slow rotation (eg, changing from one shift to another every one to two weeks) may allow for

better adaptation of the circadian rhythm than fast rotation (eg, changing shifts every 2-3

days).71,73,78,79 Slow shift rotation results in greater sleep length at home, less sleepiness on the

job, better self-reported performance, and fewer errors.74,79 In some cases, fast rotation may

increase worker satisfaction80 but the effects of such satisfaction on safety have not been

assessed. Shift rotation at an extremely slow rate approximates fixed, non-rotating shifts

(permanent night shifts, permanent day shifts). Permanent shifts are associated with better

adaptation to changes in the circadian rhythm78 and better performance than rotating shifts.79

However, daytime commitments and social obligations often prevent workers from completely

adapting to permanent night shifts and worker satisfaction is poor.71

Improving Sleep: Education about Sleep Hygiene

Good sleep hygiene, including the avoidance of alcohol and caffeine before bedtime, and

maintaining a healthy sleep environment, may aid in decreasing sleep debt and fatigue. Studies

of sleep hygiene have focused on treatment of persons with insomnia or other chronic sleep

disorders.81-83 We found no clinical studies that measure the efficacy of good sleep hygiene

among shift workers. Generally, most employers cannot dictate how their workers spend their

hours off-duty and compliance with recommendations may be poor. One study of lawenforcement officers working rotating shifts found significant increases in awareness and

knowledge after a training session on sleep hygiene practices but no change on a post-sleep
524

inventory assessed at one-month follow-up.84 The effectiveness of educational programs about

sleep hygiene to improve shift worker performance requires further study.

Lighting at Work

The body’s regulation of circadian rhythm is mediated by the effects of light and

darkness. A 1986 survey found that 7.3 million Americans work at night.71 These employees,

who work during dark hours and sleep during daylight hours, are often chronically sleep

deprived and may suffer adverse health effects,85 partially due to poor synchrony of circadian

rhythm to work schedule. Since scheduled light exposure can produce a phase shift in the

endogenous circadian rhythm,71, 86 investigators have studied changes in lighting at work and

home to improve adjustment to the shift cycle. Foret et al studied 8 young men in a sleep lab and

found exposure to bright lights during the night produced a beneficial effect on subjective

alertness.87 Czeisler and colleagues found that subjects who were exposed to bright light at night

and nearly complete darkness during the day had better cognitive performance and subjective

alertness, and longer daytime sleep (7.7 vs. 5.7 hours, p=0.01).88

Manipulation of light and dark is much easier in sleep labs than in the field,89 where

unintended exposure to bright light is common and may adversely impact attempts to alter

workers’ circadian rhythm.90 The National Aeronautics and Space Administration (NASA) has

studied the efficacy of bright lights on shuttle astronauts. Their encouraging results suggest that

alterations in circadian rhythm can be obtained upon on exposure to light at night.89,91 The

United States Nuclear Regulatory Commission has also implemented bright lighting for its night

workers and found less fatigue and better alertness on the job.92 Field studies are needed to

determine how bright artificial light affects objective measures of performance in health care

workers and medical error. Bright light may not be appropriate for all areas of the hospital. For

example, Bullough and Rea have noted that while bright light might help workers in neonatal

care units, it may also be detrimental to patients.93

Nonetheless, lighting can be a relatively inexpensive intervention using existing

equipment. Keeping lights bright at night, and educating workers about using heavy shades at

home may have an important impact on worker performance on night shifts.

Napping

Napping is common among shift workers and is perceived as a way to combat

fatigue.94,95 One study of shift workers in a steel plant found that over half reported napping at

home either before or after their shifts.94 The efficacy of naps has been studied in 3 settings:

prior to periods of sleep deprivation (prophylactic naps), during periods of sleep deprivation

(therapeutic naps) and during work hours (maintenance naps). Most studies have been

conducted in sleep labs in healthy, young, male subjects.

A number of studies in the non-medical literature have studied the efficacy of

prophylactic napping. Gillberg and colleagues studied 8 male subjects who were allowed only 4

hours of sleep at night. When subjects took a 30-minute nap in the middle of the prior day, they

had better subjective alertness, 20% improvement in vigilance performance, and less overall

sleepiness than when they had not been allowed to nap.96 Others have also found benefits of

prophylactic naps on subjective and objective measures of alertness and performance in healthy

volunteers undergoing extended periods of sleep deprivation.97-100 Bonnet and Arand studied

prophylactic versus therapeutic naps in 12 healthy young men who underwent 24 hours of sleep

deprivation to simulate sleep patterns of medical housestaff.101 One group of subjects had a 4-
525

hour prophylactic nap in the evening and caffeine during the 24 hours, while the second group

had four, 1-hour naps during the 24-hour work period and no caffeine. Those in the prophylactic

nap and caffeine group had a 15% increase in reasoning and overall improved subjective

alertness compared with the group that had only short naps. There was no impact on mood. We

identified one study of napping by medical personnel. Harma and colleagues studied 146 female

hospital nurses and nurses’ aides and found that those who napped prior to their night shifts were

less likely to report on the job fatigue.95

Most studies evaluating the efficacy of therapeutic napping during prolonged periods of

sleep deprivation have found beneficial effects when compared with no napping.102-108 On the

other hand, Gillberg and colleagues found no difference in simulated driving between the 2

groups of sleep deprived truck drivers, one group having taken a 30-minute nap during the

middle of the previous night.109

Maintenance naps are naps that occur on the job, during the shift. These naps could

compensate for daytime sleep deprivation or could bridge the nighttime low point in circadian

somnolence.110 Many Japanese industries have provided their employees with the option of on

the job napping and nearly half of nighttime shift workers take advantage of this opportunity.111

Though no systematic studies of the impact of maintenance naps exist in shift workers, one

investigation found that short naps in the middle of the night improved performance for the rest

of the shift.98 Napping over several successive shifts has not been studied.110

An important consideration in napping is the phenomena of sleep inertia, a period of

transitory hypo-vigilance, confusion, disorientation of behavior and impaired cognitive

performance that immediately follows awakening.112 Sleep inertia is well documented112-116 and

lasts up to 30 minutes after awakening.116-118 The duration of deep sleep and the time of the nap,

relative to the circadian cycle, seem most related to the severity of sleep inertia.8

 Strategies for

napping on the job to reduce fatigue should be designed to avoid possible detrimental effects of

sleep inertia. Another potential negative effect of lengthy naps is that they can disrupt the

quantity and quality of later sleep periods.119

In summary, there is strong evidence that therapeutic naps and maintenance naps combat

the effects of fatigue and sleep loss. They can help subjects adapt better to circadian rhythm

disturbances and perform better during acute sleep deprivation. Their application in the medical

field is not well known. While prophylactic and therapeutic napping result in loss of social time

at home, maintenance napping results in loss of work time. Costs associated with naps have not

been reported. The financial impact of reduced worker fatigue due to napping has not been

evaluated in medicine.

Medical Therapies

Melatonin is the major hormone responsible for circadian rhythm regulation. James et al

studied the effect of oral melatonin supplementation on circadian rhythm and adaptation to night

shifts among medical personnel.120 They and others have found no effect among medical shift

workers.121-123 Though melatonin continues to be studied for chronic insomnia and other

conditions, there currently is insufficient evidence to recommend its use to combat the fatigue

associated with changing workshifts.

Some studies have looked at the potential benefits of benzodiazepines and other sedatives

for short-term insomnia associated with shift work, but no data exist on long-term use.

Stimulants and caffeine can boost performance acutely but do not address the underlying sleep

deprivation,124 and thus are not a viable long-term solution. Furthermore, concern over side
526

effects, addiction, and performance degradation with current pharmacologic interventions makes

their use as a safety practice unlikely.

Comment

Sleep deprivation and disturbances of circadian rhythm lead to fatigue, decreased

alertness, and poor performance on standardized testing. Although data from non-medical fields

suggest that sleep deprivation leads to poor job performance, this link has not yet been

established in medicine. Although the link with fatigue seems intuitive, promoting interventions

designed to combat medical errors should be evidence-based. Limits on physician duty hours

must account for potentially detrimental effects of discontinuity in patient care. Forward rather

than backward shift rotation, education about good sleep hygiene, and strategic napping before

or during shifts may reduce fatigue and improve performance. High face validity, low likelihood

of harm, and ease of implementation make these promising strategies, although more evidence of

their effectiveness in medicine is warranted. Studies on the use of bright light in the medical

workplace are needed before it can be embraced.

As Gaba points out,125 in most high-hazard industries the assumption is that fatigue and

long, aberrant work hours lead to poor performance, and the burden of proof is in the hands of

those who believe that such work practices are safe. In medicine, concerns over discontinuity of

care, and difficulties in changing medical culture have pushed the burden of proof into the hands

of those who wish to change the status quo. Given that medical personnel, like all human beings,

probably function suboptimally when fatigued, efforts to reduce fatigue and sleepiness should be

undertaken, and the burden of proof should be in the hands of the advocates of the current

system to demonstrate that it is safe.

Finally, fatigue among medical personnel may not be fully remediable and human errors

are, in the end, inevitable. The ultimate solution for health care organizations will likely require a

systems-based approach that both limits the potential for human error and intercepts errors that

do occur before they reach patients.

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Chapter 47. Safety During Transport of Critically Ill Patients

Susana B. Martins, MD, MSc

Kaveh G. Shojania, MD

University of California, San Francisco School of Medicine

and Institute for Health Policy Studies

Background

The care of acutely ill patients routinely includes transportation, both within a given

hospital to undergo tests and procedures, and between hospitals, as patients may require transfer

to other facilities for specialized services. Critically ill patients in particular commonly require

such transfers and are at high risk for complications en route.1-4 Developing practices to reduce

or minimize this necessary risk represents a potentially important area of patient safety research.

This chapter focuses on transportation of critically ill patients by health professionals

(paramedics, nurses, physicians and/or respiratory therapists) between hospitals (to receive

higher levels of care) and within the hospital (for diagnostic or therapeutic procedures).

Stabilization before transport, in the field or in the transferring hospital, and the mode of

transferring patients from the field to specialized centers also present important research and

policy questions.5

 However, we regarded these issues as clinical research topics and quality

improvement issues for the fields of pre-hospital and emergency medicine, rather than patient

safety in general, and so do not review this literature here.

Practice Description

Intrahospital transport refers to transportation of patients within a hospital for the

purpose of undergoing diagnostic or therapeutic procedures or transfer to a specialized unit. In

the context of this chapter, this generally involves movement of critically ill patients from

intensive care areas of the hospital (including intensive care units, emergency departments,

operating theaters and recovery rooms) to areas typically not involved in the delivery of such

care (eg, a hospital radiology department). Equipment and staffing used for intrahospital

transport varies by hospital, clinical service and patient acuity. Studies of intrahospital transport

have mainly focused on the adequacy of patient monitoring and ventilator support. The specific

practices evaluated in this chapter include:

• The continued use of mechanical ventilation instead of switching to manual

ventilation. Manual ventilation involves a self-inflating bag with or without a

volumeter, while mechanical ventilation consists of a portable, time-cycled,

volume-constant transport ventilator.

• The use of specialized transfer units during intrahospital transport. The unit is

attached to the patient’s bed and contains all equipment necessary to meet the

patient’s needs (ventilation, monitoring and infusion of drugs) in the ICU and

during transport. The unit works as a stand-alone unit.

Interhospital transport refers to transportation of patients between hospitals by ground or

air ambulance. Interhospital transport teams vary widely in composition, training and experience.

The transport team does not always include a physician; even when a physician is present, his or

her training may not include skills necessary for this task.6-8 Nurses and respiratory therapists

frequently accompany critically ill patients during interhospital transport. Some paramedics
535

receive special training in skills necessary for the interhospital transport of critically ill patients.9

As with physicians, the training of nurses and respiratory therapists assigned responsibility for

interhospital transport varies widely. Equipment used during interhospital transport also varies

widely,6,7 but the practices evaluated in the literature mainly relate to the use of specialized

transport teams.

Specialized transport teams characteristically receive consistent and high levels of

training and experience in the transportation of critically ill patients,10-12 compared with teams

assembled ad hoc. Further details of the composition of these teams are presented in connection

with the specific studies reviewed below (see Table 47.1). Because of the relative paucity of

studies of practices for improving the safety of patient transport, we have reviewed the pediatric

and adult literature together.

Prevalence and Severity of the Target Safety Problem

Adverse events during transport of critically ill patients fall into two general categories:

mishaps related to intensive care (eg, lead disconnections, loss of battery power, loss of

intravenous access, accidental extubation, occlusion of the endotracheal tube, or exhaustion of

oxygen supply), and physiologic deteriorations related to critical illness (eg, worsening

hypotension or hypoxemia). Unfortunately many studies do not distinguish clearly between these

2 categories. Further complicating assessments of patient transport as a safety problem is the

confounding effect of patient selection, as patents requiring intra- or interhospital transport likely

represent a sicker patient population than unselected critically ill patients. In fact, one casecontrol study reported no differences in adverse events (equipment-related or physiologic) in

critically ill adults during the period of intrahospital transportation as compared to matched

subjects in the ICU.13

Death during transport is a rare event. The majority of studies reported no mortality

during intrahospital transport13-17 or interhospital transport,18,19 and some do not mention

deaths.21-23,24

For intrahospital transport of critically ill patients, reported rates of adverse events range

from 5.9% to 66%.13,14,16,21,22,25 (We could find no comparable reports of event rates for critically

ill children.) Much of this variation undoubtedly reflects definitional differences, but differences

in patient populations also contribute to this wide range. For instance, a prospective study of 50

high-risk adult cardiac patients reported arrhythmias in 84% of patients, with 52% of these

arrhythmias providing an indication for emergency treatment.17 These event rates are clearly

much higher than would be observed in an unselected population of critically patients. Similarly,

Insel et al showed a significantly higher incidence of hemodynamic changes requiring

therapeutic intervention when intrahospital transport involved transfers from the operating room

to the ICU compared with patients transported from the ICU to diagnostic procedures.26

In contrast to the above, the literature on adverse events during interhospital transport has

generally involved critically ill children, not adults. Reported rates of adverse events during

pediatric interhospital transport range from 0 to 75%.2,10-12,19,24,27-29 In one of these studies, a

prospective cohort design reported a morbidity ratio of 1.85 (95% CI: 1.12-3.06) for pediatric

patients transported from another hospital to the pediatric ICU (PICU) as compared with those

admitted directly (emergency room and wards). Importantly, this increased morbidity reflected

an increased rate of “intensive care events” such as plugged endotracheal tubes and loss of

intravenous access, not an increase in physiologic events. Patients experiencing such adverse

events tended to have higher morbidity scores (on the PRISM scale) and lower therapy level

(TISS) scores prior to transport. Thus, as noted above, confounding of differences in patient
536

sickness and intensity of therapy could account for much of the observed variation in transportassociated morbidity.24

Opportunity for Impact

A survey conducted in 1990 to review voluntary compliance with the American

Academy of Pediatrics (AAP) recommendations to include physicians with higher level of

training (at least 3rd year residency) reported that only 28% of hospitals with a pediatric critical

care transport team met this recommendation. All teams included a nurse with pediatric

experience and a varying degree of training, and 50% of teams included a respiratory therapist.7

Subchapter 47.1. Interhospital Transport

Study Designs and Outcomes

We identified 3 studies with at least a Level 3 study design and Level 2 outcomes (see

Table 47.1). Two of these studies10,12 involved pediatric patients. One12 reported the prospective

comparison of outcomes for high-risk pediatric patients admitted to two different ICU’s, one of

which employed a specialized transport team, while the other followed the standard practice of

using non-specialized teams. The specialized team consisted of a second-year pediatric resident

and a pediatric ICU nurse, both trained in pediatric advanced life support, and a respiratory

therapist with pediatric experience. Non-specialized teams varied in composition—a physician

was not always present and level of training in pediatric care for other personnel was not

standardized. The other pediatric study, from England,10 retrospectively compared outcomes

using a specialized team for the transport of intubated newborns from hospitals within 80 miles

to a NICU at a referral center to outcomes during a control period in which transport was

performed by ad hoc doctor/nurse teams. The specialized teams included physicians with more

years of experience and dedicated transport nurses with specialized training, as well as slight

equipment improvements (humidifier for ventilator and invasive/noninvasive blood pressure

monitoring).

The third study (the one involving adults) describes the experience of a London teaching

hospital that receives critically ill patients from other facilities by two methods: either

accompanied by the receiving hospital’s special retrieval team consisting of an ICU physician,

nurse, and medical physics technician (a technician to fix and maintain equipment) or standard

ambulance transport, with an escorting physician supplied by the referring hospital.

The 2 pediatric studies10,12 reported adverse events during transportation. We counted

adverse events related to intensive care (eg, accidental extubation) as Level 2 and physiologic

events (eg, ph < 7.2) as Level 3. (A case could be made for classifying both types of adverse

events as Level 3, as neither has a clearly established relationship to adverse events of interest).

All studies provided information on case mix in the study and control groups.

Evidence for Effectiveness of the Practice

Although of theoretical and practical concern, the literature to support the scope,

frequency and outcome of adverse events during transportation is sparse and methodologically

weak. Most studies are small descriptive studies of local practices. Factors that limit

comparability between studies include a variety of definitions for transport-related adverse

events, unclear descriptions of transport team training and experience, diverse equipment
537

availability and different scoring systems for severity of illness (APACHE II, APACHE III,

Glasgow Coma Scale, PRISM, etc). Many confounders affect the evaluation of transportation of

a critically ill patient, among them selection bias, the intervention received at primary hospital,

time spent at primary hospital, adequate stabilization before transport and duration of transport.

As shown in Table 47.1, 2 studies involving pediatric populations revealed reductions in

intensive care-related adverse events through the use of specialized teams for interhospital

transport.10, 12 In one of the studies, patients transported by the standard (non-specialized) team

were older and more likely to have trauma as a diagnosis.12 This difference in patient

populations clearly limits the ability to interpret the results, although the direction of bias this

might introduce is not clear. The other pediatric study 10 reported no significant differences in

basic clinical and demographic factors between the 2 patient populations, but did not report

PRISM scores.

The single study in adults did not report intensive care-related adverse events, but did

observe significant reductions in surrogate physiologic markers and a non-significant reduction

in mortality within 12 hours of arrival at the receiving facility. Although an observational study,

there were no differences in the patient populations in terms of demographic factors, basic

physiology measurements (FiO2, PaO2, PaCO2, PaO2/FiO2, MAP, heart rate and temperature) or

sophisticated measures of severity of illness (APACHE II, Simplified Acute Physiological

Score-SAPS II).

Studies were underpowered to detect significant mortality differences.

Potential for Harm

A delay in the transfer of critically ill patients to referral hospitals because the specialized

team is not available in timely fashion could create a potential for harm although one study

showed no delay or cancellation due to unavailability of specialist team.11

Costs and Implementation

Although no firm recommendation can be made, the costs and implementation

requirements may only be feasible for tertiary centers that have enough volume to justify the

investment in human and physical resources. Time out of hospital will vary depending on the

time required to stabilize the patient—not the focus of our study. (One study reported an increase

in stabilization time from 80-105 minutes (p<0.0001) after the implementation of a specialized

team10 and another reported no difference in duration of transport between non-specialized and

specialized team.12) The third study did not mention duration of transport.

Comment

This practice has high face validity, and what little evidence exists does support the

practice. No direct potential for harm exists, but adopting this practice without further study

might unnecessarily strain scarce health care resources. Moreover, if adopted as a standard of

care, lack of timely availability of designated transport personnel may become a factor in

delaying inter-facility transfers. For some critically ill patients, the time lost in assembling the

transport team may have a greater negative impact than the safety gained by their eventual

presence. Further research on this topic is required, fundamentally controlling for confounders

and improving outcome measures to include morbidity. Two areas that have evolved enormously

over the last 2 decades are training requirements of health personnel and the quality of transport

monitoring and ventilation equipment.
538

Subchapter 47.2. Intrahospital Transport

Study Designs and Outcomes

As shown in Table 47.2, the 3 studies of manual versus mechanical ventilation employed

a randomized (or quasi-randomized) controlled design. Randomization procedures were not

described in two studies30, 31 and used the last digit of the patient record in one study.32 The

quasi-randomized study32 implemented a crossover design using manual ventilation or transport

ventilator on one leg of the journey and vice-versa on the other leg.

Two studies reported on Level 2 and 3 outcomes30, 32 and one on level 3 outcomes,31

venous pressure, oxygen saturation, PetCO2 and mean airway pressure during transport. All

studies report on before-after variation, one study30 also reported on minute variations during the

first 8 minutes of transport (see Table 47.2). Only one study reported scores for severity of

illness (PRISM).30 Case-mix was inadequately reported in one study31 and not reported in

another.32

It is worth briefly noting a third practice which involves the use of mobile bed/monitor

units versus standard procedure for intrahospital transportation. Studies on this topic are limited

to descriptive experiences of local practice with no definition or systematic evaluation of adverse

events,17,33-35 so these practices were not reviewed further.

Evidence for Effectiveness of the Practice

The clinical significance of the hyperventilation observed in manually ventilated patients

during intrahospital transportation has yet to be determined. Mechanical ventilation was

associated with respiratory alkalosis when precision of ventilatory settings was inaccurate. No

adverse effect, (ie, morbidity) was observed as a result of the method of ventilation. Use of a

volumeter when manually ventilating a patient reduced the risk of hyperventilation. Studies were

underpowered to detect significant mortality differences.
539

Potential for Harm

Inadequate maintenance and/or precision of transport ventilator may create an opportunity for

harm.

Costs and Implementation

Portable mechanical ventilators are much more expensive, require more hours of training to

manipulate and frequent use to maintain experience. Costs were not mentioned.

Comment

One randomized controlled trial in pediatric postoperative cardiac patients showed an increase in

markers of hyperventilation for patients in the manually-ventilated group. Otherwise, manual

ventilation appears to achieve results comparable to portable mechanical ventilation. Use of a

volumeter when manually ventilating patients, and the addition of a blender to reduce FiO2 when

manually ventilating neonates,30 may adequately reduce the risks of hyperventilation, rendering

mechanical ventilation during intrahospital transport unnecessary.
540

Table 47.1. Specialized transport teams versus standard care for interhospital transport

Study Setting Study Design,

Outcomes

Main Results

Critically ill children transported to two

PICU’s in Albany, NY (specialized

transport team) and Syracuse, NY

(standard care): 1992-94

12

Level 3,

Level 2

Significant decrease adverse event

related to intensive care for patients

transported with specialized team

compared to standard care: 1/47 (2%)

vs. 18/92 (20%), p<0.05

For physiologic adverse events the

decrease was minimal and not

significant: 5/47 (11%) vs. 11/92

(12%) p>0.05

Intubated newborns transported by

specialized doctor/nurse team (increased

training and experience) to NICU in

Nottingham, England: 1994-95, and

historical control period during which

non-specialized (ad hoc) doctor/nurse

team transported patients to the same

NICU: 1991-93

10

Level 3,

Levels 2&3†

Nonsignificant reduction in

endotracheal tube-related events

(blocked or dislodged endotracheal

tubes): 0/146 (95% CI: 0-3.2%)

patients transported by specialized

teams vs. 3/73 (4.1%, 95% CI: 1.1-

12.3%) by ad hoc teams

Reductions also observed in adverse

physiologic end-points; such as

abnormal ph (p<0.05) and abnormal

temperature (p<0.001)

Critically ill adults transported to a

university ICU in London: 1996-1997;

specialist team with mobile ICU

compared with emergency ambulance

with medical escort

11

Level 3,

Levels 1&3

Mortality within 12h of arrival at the

receiving facility: 5/168 (3%, 95%

CI: 1.1-7.2%) vs. 7/91 (7.7%, 95%

CI: 3.4-15.7%)

70% reduction in number of patients

arriving in serious metabolic acidosis

when transported by a specialist team

(p=0.008): pH<7.1: 5/168 (3%) vs.

10/91 (11%)

50% reduction in number of patients

arriving in a dangerously hypotensive

state when transported by a specialist

team (p=0.03): MAP<60mmHg

15/168 (8.9%) vs. 16/91 (17.6%)
541

Table 47.2 Manual versus mechanical ventilation for intrahospital transportation

Study Setting Study

Design,

Outcomes

Main Results

30 ventilator dependent,

critically ill adults in ICU:

manually ventilated with

self-inflating bag group,

manually ventilated selfinflating bag with volumeter,

and mechanically ventilated

group (Federal Republic of

Germany)

31

Level 1,

Level 3

Pre/post transport: PaCO2 decreased from 41±2 to

34±2 (p<0.01) and pH increased from 7.40±0.02 to

7.46±0.03 (p<0.05) after manual ventilation, and

PaCO2 decreased from 40±1 to 35±2 (p<0.01) and

pH increased from 7.42±0.01 to 7.47±0.01 (p<0.01)

after using transport ventilator. No differences were

observed in the group that received manual

ventilation with a volumeter.

28 critically ill adults and

adolescents transported from

emergency department for

diagnostic procedures in a

University Hospital: manual

ventilation versus transport

ventilator (US)

32

Level 1, 

Level 2&3

Pre/post transport: PaCO2 decreased from 39±4 to

30±3 (p<0.05) and pH increased from 7.39±0.03 to

7.51±0.02 (p<0.05) after manual ventilation as

compared to conventional ventilation. No

differences between transport mechanical

ventilation and conventional ventilation. No

significant changes in oxygenation, heart rate or

blood pressure in either group.

2/14 patients had supraventricular tachycardia (no

clinical significance) during transport in the

manually ventilated group and none in the transport

ventilator group.

51 pediatric postoperative

cardiac surgery patients who

were transported within

hospital while intubated:

manually ventilated versus

mechanically ventilated

(US)

30

Level 1,

Level 2&3

Pre/post transport: Statistically significant decrease

in PetCO2 [32±1.6 to 26±1.4] in manually

ventilated as compared to mechanically ventilated

[35±1.1 to33±1.7] patients (p=0.02). No significant

difference in other ventilatory parameters, airway

pressure and hemodynamic parameters.

Minute-to-minute variations: greater amount of

fluctuation and lower mean values in PetCO2

(p<0.05) in the manually ventilated group when

compared to the mechanically ventilated group.

No clinical changes reported.
542

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1. Pollack MM, Alexander SR, Clarke N, Ruttimann UE, Tesselaar HM, Bachulis AC.

Improved outcomes from tertiary center pediatric intensive care: a statewide comparison of

tertiary and nontertiary care facilities. Crit Care Med. 1991;19:150-159.

2. Kanter RK, Tompkins JM. Adverse events during interhospital transport: physiologic

deterioration associated with pretransport severity of illness. Pediatrics. 1989;84:43-48.

3. Borker S, Rudolph C, Tsuruki T, Williams M. Interhospital referral of high-risk newborns

in a rural regional perinatal program. J Perinatol. 1990;10:156-163.

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a pediatric critical care transport team. Pediatr Emerg Care. 1992;8:1-3.

5. Young JS, Bassam D, Cephas GA, Brady WJ, Butler K, Pomphrey M. Interhospital versus

direct scene transfer of major trauma patients in a rural trauma system. Am Surg.

1998;64:88-91; discussion 91-92.

6. Dryden CM, Morton NS. A survey of interhospital transport of the critically ill child in the

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7. McCloskey KA, Johnston C. Pediatric critical care transport survey: team composition and

training, mobilization time, and mode of transportation. Pediatr Emerg Care. 1990;6:1-3.

8. Gentleman D, Jennett B. Audit of transfer of unconscious head-injured patients to a

neurosurgical unit. Lancet. 1990;335:330-334.

9. Domeier RM, Hill JD, Simpson RD. The development and evaluation of a paramedicstaffed mobile intensive care unit for inter-facility patient transport. Prehospital Disaster

Med. 1996;11:37-43.

10. Leslie AJ, Stephenson TJ. Audit of neonatal intensive care transport–closing the loop. Acta

Paediatr. 1997;86:1253-1256.

11. Bellingan G, Olivier T, Batson S, Webb A. Comparison of a specialist retrieval team with

current United Kingdom practice for the transport of critically ill patients. Intensive Care

Med. 2000;26:740-744.

12. Edge WE, Kanter RK, Weigle CG, Walsh RF. Reduction of morbidity in interhospital

transport by specialized pediatric staff. Crit Care Med. 1994;22:1186-1191.

13. Hurst JM, Davis K, Johnson DJ, Branson RD, Campbell RS, Branson PS. Cost and

complications during in-hospital transport of critically ill patients: a prospective cohort

study. J Trauma. 1992;33:582-585.

14. Szem JW, Hydo LJ, Fischer E, Kapur S, Klemperer J, Barie PS. High-risk intrahospital

transport of critically ill patients: safety and outcome of the necessary "road trip". Crit

Care Med. 1995;23:1660-1666.

15. Wallen E, Venkataraman ST, Grosso MJ, Kiene K, Orr RA. Intrahospital transport of

critically ill pediatric patients. Crit Care Med. 1995;23:1588-1595.

16. Indeck M, Peterson S, Smith J, Brotman S. Risk, cost, and benefit of transporting ICU

patients for special studies. J Trauma. 1988;28:1020-1025.

17. Taylor JO, Chulay, Landers CF, Hood W, Abelman WH. Monitoring high-risk cardiac

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18. Macnab AJ. Optimal escort for interhospital transport of pediatric emergencies. J Trauma.

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19. Barry PW, Ralston C. Adverse events occurring during interhospital transfer of the

critically ill. Arch Dis Child. 1994;71:8-11.
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20. Duke G, Green J. Outcome of critically ill patients undergoing interhospital transfer.

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30. Dockery WK, Futterman C, Keller SR, Sheridan MJ, Akl BF. A comparison of manual and

mechanical ventilation during pediatric transport. Crit Care Med. 1999;27:802-806.

31. Gervais HW, Eberle B, Konietzke D, Hennes HJ, Dick W. Comparison of blood gases of

ventilated patients during transport. Crit Care Med. 1987;15:761-763.

32. Hurst JM, Davis K, Branson RD, Johannigman JA. Comparison of blood gases during

transport using two methods of ventilatory support. J Trauma. 1989;29:1637-1640.

33. Link J, Krause H, Wagner W, Papadopoulos G. Intrahospital transport of critically ill

patients. Crit Care Med. 1990;18:1427-1429.

34. Holst D, Rudolph P, Wendt M. Mobile workstation for anaesthesia and intensive-care

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Movement of the critically ill within hospital. Intensive Care Med. 1978;4:137-143.
544

Section H. Role of the Patient

Chapter 48. Procedures For Obtaining Informed Consent

Chapter 49. Advance Planning For End-of-Life Care

Chapter 50. Other Practices Related to Patient Participation
545
546

Chapter 48. Procedures For Obtaining Informed Consent

Laura T. Pizzi, PharmD

Neil I. Goldfarb

David B. Nash, MD, MBA

Thomas Jefferson University School of Medicine

and Office of Health Policy & Clinical Outcomes

Background

The process of obtaining informed consent, whether a written document or an oral

communication is one means of ensuring that patients understand the risks and benefits of a

treatment or medical intervention. Rooted in medical ethics and codified as a legal principle, it is

based on the assertion that a competent individual has the right to determine what will or will not

be done to him or her.1 The American Medical Association (AMA) Code of Medical Ethics

establishes informed consent as an ethical obligation of physicians.2 In addition to being an

ethical obligation of physicians, legislation in all 50 states requires that patients be informed of

all important aspects of a treatment and/or procedures, although the details of these laws and

statutes differ greatly.2 Failure to obtain adequate informed consent renders a physician liable for

negligence or battery3 and constitutes medical malpractice.

To date, studies of informed consent have not investigated outcomes related to the

adequacy of the communication, insofar as this may impact patient safety.4,5 Physician-patient

communication styles have been linked to lower rates of malpractice claims.6 Nonetheless, as

noted by Levinson, malpractice claims do not reflect the actual rate of negligence. While some

have hypothesized that better informed consent could improve the patient-physician relationship,

establish trust, increase patient compliance, and provide information that could reduce medical

error, this has not been shown.7,8 In the absence of a direct link between adequate informed

consent and the reduction of medical error, the “patient safety outcome” reviewed in this chapter

is the patient’s provision of adequate informed consent.

Practice Description

Informed consent is a process through which a physician informs a patient about the risks

and benefits of a proposed therapy and allows the patient to decide whether the therapy will be

undertaken.9 It may be received in one sitting, or over a period of time,7 either orally or in

writing or a combination of the two. Informed consent procedures have been instituted in both

research and clinical medicine. In the former case, Federal regulations establish strict guidelines

for informed consent that are monitored by a special board at each institution (Institutional

Review Board). In addition, risks and adverse events that occur while research is in progress are

followed closely and reported. As such informed consent in the research setting differs greatly

from informed consent in the clinical setting.10

In clinical practice, formal efforts, such as the signing of a consent form, (presumably

preceded by adequate exchange of information), are only undertaken in some circumstances,

notably prior to major invasive procedures such as radiologic procedures and surgery. Less well

appreciated is that all medical care, including pharmacy prescriptions or laboratory tests, requires

informal informed consent, except when the patient is incompetent to make a decision or

relinquishes the right to provide it.3 Studies suggest that in practice only minimal formal efforts

are made to obtain informed consent for routine interventions.11, 12
547

Legislation governing the requirements of, and conditions under which, consent must be

obtained varies greatly from State to State. General guidelines, such as those proposed by the

AMA require patients to be informed of the nature of their condition and the proposed

procedure, the purpose of the procedure, the risks and benefits of the proposed treatments, the

probability of the anticipated risks and benefits, alternatives to the treatment and the associated

risks and benefits, and the risks and benefits of not receiving the treatment or procedure.2,3,13

As discussed below, procedures to obtain informed consent may not adequately promote

the patient’s comprehension of the information provided, rendering the consent not truly

“informed.” Interventions that may prove beneficial in improving and ensuring the patient‘s

understanding include redrafting of consent forms to reduce complexity, providing written

materials to accompany oral conversations, using multimedia or other techniques to improve

comprehension, and asking patients to recap discussions about the procedure.

Prevalence and Severity of Target Safety Problem

Procedures to obtain consent must ensure that the patient understands his or her

condition, as well as the risk and benefits of treatment, and its alternatives. It has been estimated

that less than half of the US population understands commonly used medical terms.14,15 This

“health literacy” problem may impact the ability of the patient to understand any attempts to

obtain information. In addition to lack of comprehension, procedures to obtain informed consent

may be incomplete.

Several studies have noted the various insufficiencies in procedures to obtain informed

consent. Three studies examined the completeness of physician-patient conversations in

obtaining informed consent. Braddock et al12 focused on outpatient discussions. Recognizing

that some procedures may require more discussion than others, they created a three-tiered

evaluation procedure, in which the completeness of patient-physician discussion differ according

to the complexity of the decision being discussed. Basic decisions, such as laboratory tests,

require the least in-depth discussion, covering only the patient’s role, the clinical nature of the

decision, and exploration of patient preferences. Intermediate decisions, such as changes in

medication, require a moderate depth of discussion, incorporating the Tier 1 subjects, and adding

a discussion of alternative treatments, the risks and benefits of the alternatives, and an

assessment of the patients understanding. Complex decisions such as surgery require a

discussion of the uncertainties associated with the decision, in addition to all of the

aforementioned steps. Analyzing audiotaped conversations between 1057 patients and 59

primary-care physicians and 65 surgeons, Braddock et al found that 17.2% of basic decisions

contained all required components, while none of the intermediate decisions and only one of the

complex decisions contained all of the required components. Applying only the Tier 1 basic

consent standards, 20.5% of basic decisions, 21.9% of intermediate decisions, and 38.2% of

complex decisions met all the criteria.

In a study of informed consents of surrogates for pediatric patients undergoing surgery,

coders examined audiotaped conversations with surrogates, as well as structured interview and

questionnaire data regarding the conversations. They noted that patients’ recall of the

conversations with physicians often omitted key components, such as the risks and benefits of

the procedures.16

Bottrell et al13 examined the completeness of 540 consent forms from 157 hospitals

nationwide. Of these, 26.4% included all four of the basic elements (risks, benefits, alternatives,

and other important aspects of the procedure). Eighty-seven percent noted the general possibility

of risk, but less than half provided specific information. Alternatives were noted in 56.9% of the
548

forms, and benefits appeared in 37%, though most of these were general references rather than

specific information. Although 74% of consent forms were deemed incomplete, it is unknown

whether physician-patient discussions that preceded the signing of the consent form included the

missing information.

A study by Mark et al9 found that 82.4% of 102 participants reported that they

understood everything that their physicians had described about a procedure and indicated that

all of their questions had been answered. Eighteen patients had remaining unanswered questions.

Half of this group requested more time to speak with their physicians, while the other 9 felt that

their questions were not important.

In a study by Lavelle-Jones,17 69% of patients admitted that they did not read a consent

form before signing it. In addition, approximately half of the patients awaiting treatment were

unhappy with the amount of information they received, with 21% stating that most of the

information they obtained about their surgical treatment was obtained outside of the hospital.

Consent forms have been targeted for their lack of readability. Patients with limited

reading ability are at increased risk for medical errors, due to problems reading medication

bottles, appointment slips, self-care instructions, and health education brochures.18 These

patients may also have trouble reading materials intended to aid in obtaining informed consent.

According to the National Adult Literacy Survey of 1993, approximately 40-44 million

Americans were functionally illiterate, defined as the inability to complete basic reading tasks

required to function as a member of society.19 In addition, even in educated adults, the highest

grade-level completed may not reflect actual reading comprehension level. A study of 100 adult

cancer patients found that most read at a mean grade-level equivalent of between 10th and 11th

grade. The authors suggest that forms and educational materials be written at a grade-level three

levels below the highest level of education completed by a patient.20

Several studies have examined the readability of procedure consent forms. Two studies

examined consent forms for radiologic procedures using computer generated “readability”

scores. Consent forms for use with iodinated contrast media found that 12.35 years of education

were required to read consent forms.21 A similar study of general radiologic procedure consent

forms found that they required a mean of 15 years of education. Only 16% of forms could be

understood by patients with a high-school education.11 Another Hopper et al study22 found that

general hospital consent forms were written at a grade level of 12.6. Just over half could be

understood by a patient with a high school education, less than a third by patients with a 10th

grade reading level, and just over 5% by patients with an 8th grade reading level.

Opportunities for Impact

While informed consent is a well-established practice, it often fails to meet its stated

purpose. Several methods of improving the procedures of obtaining informed consent have been

proposed, including improving the readability of consent forms,22 asking patients for recall to

establish understanding,3,23 adding additional stimuli, such as multimedia presentations24 and

providing written information.17

Lavelle-Jones17 found that elderly patients (over 60 years of age) had poorer recall than

younger patients. In addition, patients with internal locus of control—those who believed their

health was in their own control—were better informed than those with an external locus of

control. Patients with above average IQ exhibited better recall. These findings could indicate “atrisk” groups that interventions may target.

One author argues that an important opportunity for impact is to change the model of

implementing informed consent from a single event approach to a process approach.7 Currently
549

obtaining informed consent often revolves around the signing of the consent form. Although this

approach clearly delineates the responsibility of health care providers, provides documentation

of the consent, and fits easily into the current provider structure, it often results in patients failing

to actually comprehend the information and reinforces physicians’ conception that the consent

ritual is futile. In contrast, a process model involves the physician providing information over

time, establishing a better patient-physician relationship and better comprehension of medical

care. As of yet there is no data to support these suppositions.

Since the definition of adequate informed consent is debatable, the number of individuals

currently not receiving interventions to obtain adequate informed consent is likely to be quite

high, but is not known.

Study Design, Outcomes and Effectiveness of Various Approaches

Improving Readability of Consent Forms and Education Materials

In order to ensure that patients understand the procedure to which they are consenting, it

is important that all materials be presented in a comprehensible manner. Consent forms are

written with relatively complex sentence structure and vocabulary, making it difficult for the

average adult to interpret the information. In addition, providing consent forms in the primary

language of patients may improve consent procedures. However, we located no studies

examining the effectiveness of such practices.

Structured Discussions

Informed consent is often obtained during informal discussion between physicians or

nurses and patients, and (as discussed above), these discussions frequently do not cover all of the

relevant information.12 Two studies examined the use of a structured interview format in

providing information to patients. Solomon et al25 studied 36 patients receiving cardiac

catheterization for the first time at a Veterans hospital. Patients were randomized into two groups

(Level 1 design). Both groups were briefed by a cardiologist regarding the procedure (standard

care). In addition, the experimental group received a 30-minute structured teaching session with

a nurse to discuss all aspects of the procedure, including the purposes, techniques, sensations,

risks and benefits. Patients in the experimental group also received an illustrated guide to

cardiovascular procedures and an educational pamphlet. All subjects were tested using a 13-item

questionnaire covering the information that should have been imparted during informed consent

procedures (Level 3 outcome). The intervention group scored significantly better than the control

group (11.5 vs. 8.9).

In a later study, Dawes et al26 studied 190 hospitalized patients undergoing ENT surgery.

Patients were assigned to one of 4 groups. Groups 1 and 2 were assigned at different times

(Level 2 design), while groups 3 and 4 were randomly assigned (Level 1 design). Group 1 had

no consent interview until after assessment at the conclusion of the study. Group 2 engaged in an

informal interview with a physician (reflecting current practice), during which the number of

complications discussed was recorded. Group 3 engaged in a structured interview with a

physician, covering the purpose and technique of the procedure, complications, sensations,

alternatives, and benefits (a checklist was used as a guide). The final group, Group 4, engaged in

the same structured interview, except that the patient was provided with a copy of the checklist

and allowed to take it with them after the interview. Patient anxiety was assessed following

consent using a visual analog scale, then reassessed at an interview, given 4 hours later. At the

later interview, patients were asked to recount orally the operation name, describe what would be
550

done, list complications, and state whether they understood the information given to them (Level

3 outcome). All but Group 1 (control group) patients showed a drop to normal anxiety after

informed consent. Group 2 (informal discussion) remembered proportionately more

complications mentioned in the informal interview, although fewer complication were covered.

Groups 3 and 4 recalled more total complications than Group 2. There was no differences

between Groups 3 and 4 (structured interviews).

Asking for Recall

A simple method of determining whether a patient understands information regarding a

procedure is to ask the patient to recount what he or she has been told.3 Two studies examined

this intervention, using a randomized controlled trial design (Level 1 design). In the first study,

informed consent was solicited from 50 patients undergoing percutaneous lung biopsy.23

Twenty-seven patients in the control group were offered the standard procedure for obtaining

informed consent: approximately 30 minutes prior to the procedure, the physician described the

procedure in detail, including its risks and benefits. Four complications were specifically

described, along with their relative risks. Patients were asked to sign a standard consent form.

Twenty-three patients received the same procedure, but in addition, they were asked to describe

all 4 potential complications. The procedure was repeated until all patients in the intervention

group could recount all of the complications. This modified procedure usually took less than 5

minutes extra compared with the traditional approach. Patients were interviewed 2 hours after

the procedure was completed. Patients in the modified consent group had better recall (Level 2

outcome) than patients in the control group (56% vs. 14% with high recall (recalling 3-4 out of 4

risks), and 13% vs. 44% with low recall (recalling 0-1 out of 4 risks)).

A second study examined verbalization in 20 patients undergoing anterior cruciate

ligament (ACL) reconstruction.27 Patients were randomly assigned to 2 groups. Both groups

received the standard education for ACL reconstruction, which included the use of a 3-D model

of the knee, discussion with a physician about the procedure, and obtaining informed consent.

The experimental group (8 subjects) also were asked to repeat back the risks of the procedure

until they could accurately recall all risks discussed. One-month later, recall regarding the

information received was tested using a 3-item questionnaire (Level 2 outcome). All 8 in the

experimental group answered all questions correctly, while only four out of the 12 in the control

group answered all questions correctly (p=0.03).

Use of Visual or Auditory Learning Aids

Adding additional stimuli may increase the ability of the patient to understand

information being conveyed or increase retention of that information. For instance, use of visual

diagrams may make a procedure easier to understand. Multi-media may also promote better

comprehension. Three studies have examined the addition of visual stimuli for informed consent.

One study of patients undergoing back surgery examined the impact of a diagnosis-specific

videodisk program on patient outcomes.24 Patients (n=393) who were candidates for elective

back surgery (primarily for herniated disc and spinal stenosis) were randomized to two education

groups (Level 1 design). The control group received a written booklet regarding the surgical and

non-surgical treatments for herniated disc and spinal stenosis, a description of expected

outcomes, and a short self-test on the booklet information. Patients in the experimental group

also received the booklet, but in addition viewed a videodisk program. The program allowed a

patient to enter their diagnosis and age and receive customized information on the alternative

treatments, discussion of the diagnoses (and the ambiguities of diagnosis), and interviews from
551

patients that had been treated surgically and non-surgically. At the end the patient was provided

with a printout of outcome probabilities. Patients in the experimental group were slightly more

likely to report that they had all the information they wanted (Level 3 outcome). Rates of

patients consenting to surgery for herniated disk (32% vs. 47%) and other diagnoses (5.4% vs.

14.0%) were lower in the videodisk group.

Hopper et al28 also tested an interactive video program, although the tested program was

computer based. One-hundred and sixty outpatients referred for IV contrast media studies were

stratified by age, sex, and previous exposure to contrast media, then randomized to receive either

a written consent form, or an interactive computer-based video (Level 1 design). Subjects in the

control group received a consent form designed to be read at an eighth grade reading level.

Subjects in the experimental group viewed a video in which a physician used identical words as

the consent form to inform subjects about the procedure and risks. Subjects then had an option of

hearing more about the risks. If subjects chose not to hear additional information, they were

provided with printouts of the risks (with the minimal information already given). Otherwise

subjects were provided with printouts certifying that they had completed the program. All

subjects were tested using a 7-item questionnaire regarding the procedure and risks (Level 2

outcome). Patients that viewed the video responded correctly more often than the control group

when asked about general aspects of the procedure. Female patients in the video group also

responded correctly more often to questions about risks, although this finding did not hold for

male patients. The video did take approximately 1.6 minutes of additional time to complete, and

there was no difference in patients desire for additional knowledge between the groups (Level 3

outcome).

One final study did not use an interactive video, but tested whether providing information

via video was superior to providing information via an informal discussion with the physician

(standard practice).29 Two-hundred and twenty four subjects referred for colonoscopy were

stratified into previous or no previous colonoscopy, then randomized into 3 groups (Level 1

design). The control group had a structured discussion with a physician, in which the physician

covered the same information covered in the video according to a checklist. The video-only

group watched a 5-minute videotape, in which a physician described the procedure, and its risk

and benefits. The third group (video and discussion), watched the video and then engaged in a

structured discussion with a physician. All patients were tested using a 13-item questionnaire

(Level 2 outcome). Both video groups gave more correct responses than the discussion-only

group, although they did not differ from each other. In addition, patient anxiety levels were

measured using the State-Trait Anxiety Inventory (Level 3 outcome). There were no differences

among the 3 groups.

Providing Written information to Patients

Providing written information to patients regarding their diagnoses, proposed treatments,

and other information given during informed consent discussion allows the patient to refer back

to such information, and possibly increases comprehension. One early study compared the thencommon practice, informal interview between patient and doctor, with provision of a written

consent form.30 Eighty patients, referred for a first excretory urography, were randomly assigned

to 2 groups (Level 1 design). The control group received standard care, the informal interview.

The experimental group received the same interview along with a detailed written consent form

to read and sign. Patient clinical reactions and side effects were monitored (Level 1 outcome).

One to 3 days after the procedures, patients retrospectively rated discomfort, fear or

apprehension, and understanding of the procedure (Level 3 outcome). Patients also completed an
552

8-item knowledge examination covering the information on the consent form (Level 2 outcome),

or in the informal interview. Experimental subjects scored significantly better (p=<0.01) than

control subjects for the knowledge exam (scoring 73% vs. 48%), but did not differ in their

discomfort, perception of the procedure, or anxiety.

Some investigators have proposed that patients should receive written consent forms days

before receiving a procedure. Neptune et al31 studied 160 subjects referred for a contrast media

radiology exam. The patients were stratified by age, sex, and previous exposure to constrast

media, and then were randomized within the strata into 2 groups (Level 1 design). The control

group received a simple consent form (designed such that it could be read with an eighth grade

education), 15-60 minutes before the procedure, consistent with standard care. Patients in the

experimental group received the same consent form 24-72 hours before the procedure, and were

called one day in advance to remind them to read the form. Subjects’ knowledge concerning

their procedures was tested using a 7-item questionnaire (Level 2 outcome). Overall, there were

no significant differences between the two groups on either a knowledge or satisfaction score.

In a British study,17 265 patients undergoing intrathoracic, intraperitoneal, or vascular

procedures, were assigned to one of 2 consent groups (Level 2 design). The control group was

provided with an oral explanation of their disease and the proposed procedures. Members in the

experimental group were provided with the same information, and also provided with an

“operation card” detailing the same information. Patients were given 30 minutes to review the

cards before signing the consent form. Patients were interviewed for recall (Level 2 outcome)

immediately after consent (1 hour), the day of discharge, 4-6 weeks post-discharge, and at 6

months post-discharge. Control and experimental groups did not differ, except on the day of

discharge (p<0.0001). The only significant factor in predicting recall was the age of the patient,

as older patients had poorer recall than younger patients, even when controlling for

psychological factors. Written information did not appear to aid in recall for older patients at

any time point.

Two other studies provided written information to patients, although this was combined

with structured teaching programs. These studies are reviewed under “Structured Discussions”

above.25, 26

Comment

While much has been written regarding informed consent and the ethical obligations of

providers to obtain proper informed consent, serious shortcomings have been reported. However,

very little literature has examined the impact of different procedures for obtaining informed

consent on the quality of the consent obtained. The weight of the literature suggests that the

value of informed consent can be modestly enhanced by augmenting standard provider-patient

discussions with additional learning and retention aids (written or videodisk materials).

Moreover, the process of consent can be mildly improved by using structured interviews and by

asking patients to recall and re-state key elements of the discussion. In addition to the ethical

imperative of informed consent, it may be that informed patients are less likely to experience

medical errors by acting as another layer of protection (as when a patient is able to inform

providers about his or her correct medications or the correct surgical procedure he or she is to

undergo). More research is needed to establish the best practices to improve informed consent,

and to test the impact of such practices on patient safety.
553

References

1. Edwards SJ, Lilford RJ, Thornton J, et al. Informed consent for clinical trials: in search of

the "best" method. Soc Sci Med. 1998;47:1825-40.

2. American Medical Association. Informed consent. American Medical Association. April

11, 2001.

3. Pape T. Legal and ethical considerations of informed consent. AORN J. 1997;65:1122-7.

4. Stewart MA. Effective physician-patient communication and health outcomes: a review.

CMAJ. 1995;152:1423-33.

5. Greenfield S, Kaplan S, Ware JE, Jr. Expanding patient involvement in care. Effects on

patient outcomes. Ann Intern Med. 1985;102:520-8.

6. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication. The

relationship with malpractice claims among primary care physicians and surgeons.

7. Lidz CW, Appelbaum PS, Meisel A. Two models of implementing informed consent. Arch

Intern Med. 1988;148:1385-9.

8. Kuyper AR. Patient counseling detects prescription errors. Hosp Pharm. 1993;28:1180-1,

1184-9.

9. Mark JS, Spiro H. Informed consent for colonoscopy. A prospective study. Arch Intern

Med. 1990;150:777-80.

10. Code of Federal Regulations. Title 45: Public Welfare. .Revised June 18, 1991.Effective

August 19, 1991.

11. Hopper KD, TenHave TR, Hartzel J. Informed consent forms for clinical and research

imaging procedures: how much do patients understand? AJR Am J Roentgenol.

1995;164:493-6.

12. Braddock CH, 3rd, Edwards KA, Hasenberg NM, et al. Informed decision making in

outpatient practice: time to get back to basics. JAMA. 1999;282:2313-20.

13. Bottrell MM, Alpert H, Fischbach RL, et al. Hospital informed consent for procedure

forms: facilitating quality patient-physician interaction. Arch Surg. 2000;135:26-33.

14. Boyle CM. Difference between patients' and doctors' interpretation of some common

medical terms. Br Med J. 1970;1:286-9.

15. Cole R. The understanding of medical terminology used in printed health education

materials. Health Educ J. 1979;38:111-21.

16. Lashley M, Talley W, Lands LC, et al. Informed proxy consent: communication between

pediatric surgeons and surrogates about surgery. Pediatrics. 2000;105:591-7.

17. Lavelle-Jones C, Byrne DJ, Rice P, et al. Factors affecting quality of informed consent.

BMJ. 1993;306:885-90.

18. Baker DW, Parker RM, Williams MV, et al. Health literacy and the risk of hospital

admission. J Gen Intern Med. 1998;13:791-8.

19. Kirsch I, Jungblut A, Jenkins L, et al. Adult literacy in America: a first look at the results

of the national adult literacy survey. Washington, DC: National Center for Education, US

Department of Education; 1993.

20. Jubelirer SJ, Linton JC, Magnetti SM. Reading versus comprehension: implications for

patient education and consent in an outpatient oncology clinic. J Cancer Educ. 1994;9:26-

9.

21. Hopper KD, Lambe HA, Shirk SJ. Readability of informed consent forms for use with

iodinated contrast media. Radiology. 1993;187:279-83.
554

22. Hopper KD, TenHave TR, Tully DA, et al. The readability of currently used

surgical/procedure consent forms in the United States. Surgery. 1998;123:496-503.

23. White CS, Mason AC, Feehan M, et al. Informed consent for percutaneous lung biopsy:

comparison of two consent protocols based on patient recall after the procedure. AJR Am J

Roentgenol. 1995;165:1139-42.

24. Deyo RA, Cherkin DC, Weinstein J, et al. Involving patients in clinical decisions: impact

of an interactive video program on use of back surgery. Med Care. 2000;38:959-69.

25. Solomon J, Schwegman-Melton K. Structured teaching and patient understanding of

informed consent. Crit Care Nurse. 1987;7:74-9.

26. Dawes PJ, O'Keefe L, Adcock S. Informed consent: the assessment of two structured

interview approaches compared to the current approach. J Laryngol Otol. 1992; 106:420-4.

27. Wadey V, Frank C. The effectiveness of patient verbalization on informed consent. Can J

Surg. 1997;40:124-8.

28. Hopper KD, Zajdel M, Hulse SF, et al. Interactive method of informing patients of the risks

of intravenous contrast media. Radiology. 1994;192:67-71.

29. Agre P, Kurtz RC, Krauss BJ. A randomized trial using videotape to present consent

information for colonoscopy. Gastrointest Endosc. 1994;40:271-6.

30. Winfield AC, Ford CV, James AE, et al. Response of patients to informed consent for

excretory urography. Urol Radiol. 1986;8:35-9.

31. Neptune SM, Hopper KD, Houts PS, et al. Take-home informed consent for intravenous

contrast media: do patients learn more? Invest Radiol. 1996;31:109-13.
555
556

Chapter 49. Advance Planning For End-of-Life Care

Nina Garas, MD

Emory University School of Medicine

Steven Z. Pantilat, MD

University of California, San Francisco School of Medicine

Background

Physicians and other health care workers have long struggled with decisions regarding

care for patients at the end of life. An important component of this care involves assessing and

understanding patient preferences for care through ongoing discussions with competent adult

patients and/or their family members or surrogates. Advance care planning protects patient

autonomy and helps to assure that their health and medical treatment wishes are implemented.

Good communication at the end of life can also help patients achieve closure and meaning in the

final days of their life.

Over the past 20 years, public consciousness regarding planning for end-of-life care has

been raised through several seminal court cases, such as those involving Karen Ann Quinlan and

Nancy Cruzan. These cases and the public interest they helped engender led to legislation

promoting patients’ rights to determine their care at the end of life. For example, Natural Death

Acts (statutes passed by State legislatures that assert a person’s right to make decisions regarding

terminal care) have helped promote the use of living wills (described below).1

 In addition, in

1990 the Federal Patient Self-Determination Act (PSDA) was passed by Congress to encourage

competent adults to complete advance directives. The PSDA requires hospitals, nursing homes,

health maintenance organizations, and hospices that participate in Medicare and Medicaid to ask

if patients have advance directives, to provide information about advance directives, and to

incorporate advance directives into the medical record.2

Advance directives are any expression by a patient intended to guide care, should they

lose their medical decision making capacity. Although both oral and written statements are valid,

the added effort required to complete written statements gives them greater weight. In addition to

their use when patients lose competence, advance directives also help patients consider the type

of care they would want in the future, even if they retain decision making capacity. Advance

directives have legal validity in almost every State.

There are 2 principal forms of written advance directives: living wills and durable powers

of attorney for health care. A living will is a document that allows an individual to indicate the

interventions he or she would want if he or she is terminally ill, comatose with no reasonable

hope of regaining consciousness, or in a persistent vegetative state with no reasonable hope of

regaining significant cognitive function. A durable power of attorney for health care (DPOAHC) is a more comprehensive document that allows an individual to appoint a person to make

health care decisions for him or her should he or she lose decision making capacity.

Prevalence and Severity of the Target Safety Problem

Respecting patient preferences regarding end-of-life care requires a well-coordinated

approach. Problems can arise in both documenting patient preferences and ensuring that

preferences are available and respected at the time they are needed. In addition, inadequate

communication with patients can compromise the goal of respecting patient preferences for endof-life care through a variety of mechanisms.
557

Failure to Document Preferences

The PSDA was a legislative solution (see Chapter 55) designed to increase rates of

completed advance directives. Although there was initial hope that PSDA would markedly

increase rates of advance directive documentation, by the early 1990s it was clear that the impact

was small. At that time, a large multicenter randomized trial, the Study to Understand Prognoses

and Preferences for Outcomes and Risks of Treatments (SUPPORT), was undertaken to improve

advance care planning. SUPPORT represents one of the largest and most comprehensive efforts

to describe patient preferences in seriously ill patients, and to evaluate how effectively patient

preferences are communicated. SUPPORT cost 28 million dollars and enrolled 9100 seriously ill

patients. In SUPPORT, a trained nurse facilitator provided prognostic information to patients and

medical staff, discussed patient preferences with patients and families, and facilitated

communication between patients and physicians.

Neither the PSDA legislation nor the SUPPORT intervention had major impacts on the

documentation of patients’ preferences regarding end-of-life care. Teno et al reported on the

documentation of advance directives at 3 points: before PSDA, after PSDA, and after the

SUPPORT intervention. The percentage of patients with an advance directive was unchanged in

all 3 groups, but documentation of those directives increased at each stage, from 6% to 35% to

78% in the SUPPORT intervention group. Despite this increase in documentation, only 12% of

patients with an advance directive had talked with a physician when completing the document

and only 25% of physicians were aware of their patients’ advance directives.3

 SUPPORT found

that only 23% of seriously ill patients had talked to their doctors about their wishes concerning

cardiopulmonary resuscitation (CPR) and that patient-physician discussions and decisions were

uncommon even in seriously ill patients whose death was predictable.4

 Another study that

surveyed elders in community settings found that the vast majority (81%) stated their desire to

discuss their preferences with their physicians if they were terminally ill, but only 11% had done

so.5

 As these studies demonstrate, patients often want to talk about death and dying but expect

physicians to bring up the issues.6

Ensuring that Preferences are Available and Respected

Even when advance directives are prepared, studies show they often do not change

interventions at the end of life.3,7 Advance directives are frequently not available, recognized or

applied, nor do they help reduce hospital resource use. There are multiple reasons why advance

directives may go unrecognized.8

 Admitting clerks may fail to document or incorrectly

document the status of a directive on admission to the hospital. Patients and families often do not

inform the hospital physician or admitting clerk about their advance directives, or fail to bring

documentation to the hospital.8

 In one survey of 200 patients, only 18% had filled out an

advance directive and of these, 50% had secured the only copy in a safety deposit box!9

 A copy

of the advance directive is often not transferred from the nursing home to the hospital on

admission. In a study by Morrison, physicians documented advance directives or discussions

with appointed proxies about treatment decisions in only 11% of admission notes.8

Although the goal of advance directives is to ensure that patients receive treatment that is

consistent with their preferences, to date there is no evidence that documenting advance

directives leads to this outcome. In SUPPORT, there was no evidence that increasing the rates of

advance directives resulted in care more consistent with patients' preferences.10 This finding was

concordant with a study of nursing home patients and their family members regarding

preferences for aggressive treatment at the end of life. There, 25% of patients received care that
558

was inconsistent with their previously expressed wishes.11 The problem may not be the substance

of advance directives per se, but rather in the manner in which clinicians approach them.

Physicians may be hesitant to initiate discussions of advance directives with patients, especially

early in the course of an illness.12

Despite these shortcomings, advance directives remain the best available approach for

helping patients plan future care. These discussions, difficult as they are, help ensure that

patients receive care consistent with their values and goals, spare the patient inappropriate

interventions, and help maintain dignity during the dying process.

Physician Communication

In order to improve the quality of end-of-life care, physicians need to effectively

communicate with their patients and understand their preferences for care. Several studies have

documented imperfections in physician-patient communication.13,14 Several studies have

demonstrated that physicians often misunderstand or are unaware of their patients’ preferences

for care.15,16 Furthermore, physician prediction of patients’ preferences for resuscitation are no

better than random.3,14

In summary, the published literature demonstrates significant problems in all areas

crucial to advance care planning and ascertainment of patient preferences, transmission of

information to appropriate care settings, and respecting those preferences. The provision of

unwanted end-of-life care is an adverse event that can potentially be avoided by the

implementation of effective patient safety practices.

Opportunities for Impact

Patients with chronic or life-limiting illnesses make up a large proportion of the adult

primary care population. Almost three-quarters of the 2.3 million Americans that die each year 

are 65 years of age or older. By the year 2030, people older than 65 will compromise 20% of the

total population (70 million people), compared with 13% in 1994. Today’s average life

expectancy is 75.5 years, and the leading causes of death are heart disease, cancer and stroke.

Data from 1995 estimated that these causes accounted for 62% of all deaths and 67% of deaths

for those age 65 and over.17 The overall picture is of an aging population, with many individuals

living for several decades (often with chronic diseases) after the possibility of death becomes

more than theoretical.18

SUPPORT documented serious problems with terminal care. Physicians did not

implement patients’ refusals of interventions. When patients wished to forgo CPR, a do not

resuscitate order was never written in about 50% of cases.4

 While 90% of Americans say they

want to die at home, 4 out of 5 die in a hospital or other health care facility. The SUPPORT

study showed that only 35% of the study patients had an advance directive. These patients had

an approximate six month mortality rate of 50%.

Physicians and the public also commonly overestimate the effectiveness of CPR. In

reality, in-hospital cardiac arrests have a survival rate of about 15%. For patients over 65 the

survival rate is about 10-11%, and 3.5% for patients over age 85.19 Elderly nursing home patients

with out-of-hospital arrest only have 1-2% survival.20 Studies have shown that when patients are

aware of the real survival rates for CPR, they are less likely to desire this intervention.
559

Evidence for Effectiveness of the Practice

Documenting Preferences and Ensuring that they are Available and Respected

A Physician Order form for Life-Sustaining Treatment (the POLST)

In the mid-1990s, a task force of ethicists and clinicians at the Oregon Health Sciences

University developed a new Do Not Resuscitate (DNR) order form called POLST (Physician

Orders for Life-Sustaining Treatment). POLST is a comprehensive two-page order form that

documents a patient’s preference for life-sustaining treatments. The form is designed to record a

patient’s wishes clearly and simply. The accompanying POLST wallet card is included as Figure

49.1; the complete POLST form and materials can be obtained from the Oregon Health Sciences

University’s Center for Ethics in Health Care (http://www.ohsu.edu/ethics/polst.htm).

Tolle et al examined the extent to which POLST ensured that nursing home residents’

wishes were honored for DNR orders, and for hospital admission only if comfort measures

failed. None of the 180 patients who completed POLST received CPR, ICU care, or ventilator

support, and only 2% were hospitalized to extend life. The study subjects had low rates of

transfer for aggressive life-extending treatments and high levels of comfort care.21

Since 1995, more than 220,000 copies of POLST have been distributed throughout the

State. Data from 1999 suggest, albeit circumstantially, that this initiative may be working. In

1996, Oregon’s in-hospital mortality rate was 31%, compared with the national average of

56%.22

Lee et al studied the effectiveness of POLST in a Program of All-Inclusive Care for the

Elderly (PACE) in Portland, Oregon. They retrospectively reviewed POLST instructions for each

of the 58 participants and whether or not each of the treatments addressed by the POLST was

administered in the final 2 weeks of life. The POLST specified DNR for 50 participants (93%);

CPR use was consistent with these instructions for 49 participants (91%). The participants also

designated the level of care they preferred as either comfort care, limited, advanced, or full

intervention. Interventions administered were at the level specified in only 25 cases (46%), with

less frequent deviations in antibiotic administration, administration of IV fluids, and placement

of feeding tubes. The investigators concluded that the POLST effectively limits the use of some

life-sustaining interventions, but that further investigation is needed into the factors that lead

physicians to deviate from patients' stated preferences about other treatments.23
560

Administrative Initiatives to Ascertain Preferences on Admission to Hospital or Nursing

Home

In addition to POLST, some medical centers have developed admission order forms to

document patient preferences regarding end of life. These forms require health care personnel to

inquire about advance directives, resuscitation preferences, artificial fluids and nutrition, etc.

This approach, promoted by the passage of the PSDA, may be effective in promoting providerpatient discussions about end-of-life wishes and prevent unwanted treatments. However, there

are no data documenting the effectiveness of this strategy.

Ascertaining Preferences in the Outpatient Setting

As with other forms of computerized decision support (Chapter 53), computer-generated

reminders for primary caregivers can increase the rates of discussion of advance directives and

completion of advance directive forms among elderly outpatients with serious illnesses. Dexter

et al performed a randomized, controlled trial to test the effectiveness of computerized

reminders. The participants were 1009 patients and 147 primary care physicians in an outpatient

setting. Physicians that received computer-generated reminders that recommended discussion of

one or both of 2 types of advance directives were compared with physicians who received no

reminders. Physicians who did not receive reminders (controls) discussed and completed

advance directives in only 4% of the patients On the other hand, physicians who received both

types of reminders discussed (24%) and completed (15%) advance directives significantly more

frequently.24

The Portability of Advance Directives between Hospitals and Nursing Homes

Ghusn et al retrospectively studied the relationship between inter-institutional

communication and continuity of advance directives from hospital to nursing home settings.

Having a hospital discussion about advance directives or having a hospital DNR order were

associated with a higher rate of advance directive discussions in nursing homes. Hospital DNR

orders were continued for 93% of patients discharged to the hospital-affiliated nursing home and

41% of patients discharged to the community nursing home. Specific communication of hospital

DNR status to the receiving nursing homes was associated with better continuity of DNR orders.

The authors concluded that completing advance directives before patients are discharged to

nursing homes, communicating advance directives to the receiving home, and providing followup discussions at the nursing home might improve the continuity of advance directives between

hospitals and nursing homes.25

Practices to improve physician-patient communication and physician understanding of patient

preferences

Training for Physicians

Physician education is an attractive way to improve end-of-life care. Physicians often do

not communicate about advance care planning because many have not been taught the relevant

communication skills and have learned them only through personal experience.26 A study by

Tulsky et al revealed that when physicians discussed end-of-life issues with their patients, they

spoke twice as much as they listened and did not routinely explore patients’ values.26

Until recently, training for health care providers in palliative care and respecting patient

preferences, and materials to support such training, were inadequate. For example, recent studies
561

have demonstrated that most medical and nursing textbooks insufficiently cover end-of-life care

issues.27 Increasingly, resources (including textbooks, palliative care journals or journal series,28

Web sites and training programs) are filling this educational void. The American Medical

Association has developed an extensive physician training program titled Education for

Physicians on End-of-Life Care (EPEC).29 This curriculum teaches fundamental skills in

communication, ethical decision making, palliative care, pain and symptom management, and

other end-of-life treatment issues.30 The Robert Wood Johnson Foundation initiative, “Last

Acts,” is another ambitious effort to educate both patients and providers.

Other educational training programs exist for physicians and students as well.30

Physicians can receive formal training by attending conferences on decisions near the end of life,

case management meetings regarding individual patients, and seminars on communication skills

with individual feedback to physicians on their performance.31 Physicians with expertise in this

area often conduct seminars to educate physicians. Buckman and Lo have developed guides for

specific end-of-life discussions, such as breaking bad news and the act of active listening and

empathy.32, 33

As attractive as these educational programs are, none have been studied for their impact

on changing practice or outcomes. Although common sense might tell us that such programs are

likely to be effective, the generally unimpressive relationship between professional education

and outcomes or process change (Chapter 54) provides grist for uncertainty pending formal

effectiveness studies.

Palliative Care Services

Specialized palliative care programs have become increasingly common in the health

care system. Physicians and other health care providers, including nurses, social workers,

chaplains, and others are available to coordinate care and provide consultation for terminally ill

patients in hospices, hospitals, nursing homes or patient’s homes. The palliative care service also

plays an important role in fostering communication among providers, patients, and families.

Data regarding effectiveness are lacking.

Hospitalist Systems

Hospitalist physicians may improve end-of-life care in hospitals. Hospitalists, by virtue of their

large inpatient volumes, should become increasingly facile with ascertaining patient preferences

regarding end-of-life care. Hospitalists have a unique opportunity to approach patients, since an

admission generally signals either a worsening of the patient’s current condition or a new

diagnosis. The hospitalist may have more time to spend with patients and is available over

consecutive hospital days to answer any questions. A routine discussion of advance directives by

hospitalists can help improve the quality and efficiency of patient care.34 On the other hand,

patients may have a long-standing trusting relationship with their primary care physicians, and

may have expressed their wishes to this physician prior to hospitalization. This possibility

highlights the importance of hospitalist-primary care provider communication, particularly

concerning end-of-life issues.34

One retrospective chart review study of 148 patients dying at a community teaching

hospital has examined the impact of hospitalists on end-of-life care. In this study, patients cared

for by hospitalists were significantly more likely to have had a documented family meeting (91%

vs. 63% for patients of community-based primary physicians). About two-thirds of patients in

both groups requested limitations in the level of care by the time of death. Of these, patients of

hospitalists were significantly less likely to have documented pain, dyspnea, or anxiety in the 48
562

hours prior to death (57% vs. 75%). Whether these differences reflect differences in the quality

of care, the completeness of documentation, or underlying patient differences requires further

study.35 Although the hospitalist movement holds promise for improving end-of-life discussions,

more research is needed to determine whether this promise will be met.

End-of-Life Education for the Public

Extensive public awareness and educational programs are necessary to create a foundation for

successful end-of-life conversations in patients with advanced illness. Broadcasts, such as the

PBS-Bill Moyers special “On Our Own Terms,” may help the public appreciate the experience

of terminal illness, and the complex choices that are faced. Such presentations may encourage

viewers to discuss how they might manage a similar situation, and explore their own fears and

concerns about dying. There are no data regarding the effectiveness of public education to

improve advance care planning.

Other Locally Successful Advance Care Planning Programs

Individual programs to implement patient preferences have emerged around the country.

Limited data suggest that they may be effective, and bear further examination as to their

portability to other programs and settings and their durability over time.

• “Respecting Your Choices” Program

Gundersen Lutheran Medical Center in La Crosse, Wisconsin has worked on community-wide

programs to improve advance care planning with an initiative called “Respecting Your Choices.”

This program used patient and family education, community outreach, education for nonmedical professionals, standard training sessions, and standard methods for documenting and

tracking advance directives. Hammes et al reported that 85% of patients in the intervention

group had written advance directives at death, executed on average 1.2 years before death. Of

these directives, 95% were in the medical record. Virtually all patients (95%) reported that the

interview process was meaningful. The patients felt that they benefited from improved

communication with loved ones and with health care providers.36

• Dayton VA Initiative

The Dayton (Ohio) VA Medical Center aimed to increase the number of veterans who

participated in advance care planning. VA patients and their families received a patient education

booklet and a video on advance care planning. The VA also developed discussion guidelines for

providers, initiated an advance care planning clinic, and initiated a bereavement support group.

In a 12-week period, advance care planning discussions and follow-up increased from about 15%

percent of charts to almost 90%.37

• “Let Me Decide” Program

Molloy et al examined patient satisfaction with decision making and health care costs

after systematically implementing an advance directive program in nursing homes. The “Let Me

Decide” program included educating staff in local hospitals and nursing homes, residents, and

families about advance directives and offering competent residents or next-of-kin of mentally

incompetent residents an advance directive. The researchers reported that systematic

implementation of this program reduced hospitalizations and aggressive care for nursing home

patients who did not want that level of intervention. It also reduced utilization of health care

services without affecting satisfaction or mortality.38
563

Costs and Implementation

Estimating the cost of ascertaining and respecting patient preferences is difficult since

improvements in this area may require major changes in the structure of the health care system.

Institutional barriers, the culture of medicine, patient attitudes, time constraints physicians face

with office visits may all play a role in implementation and may inhibit change.26 Barriers to

implementation include complacency on the part of the physician and patient, fear of political

controversy, diffused responsibility, and absence (or perverse) financial incentives for providers

and institutions. The surprising ineffectiveness of the SUPPORT intervention, which cost over

28 million dollars, demonstrates how difficult it is to make major improvements in this area.

Nevertheless, improving our ability to respect patient preferences is valuable in its own right and

may ultimately prove to be cost-effective, since some patients will choose to forego high

technology and expensive care at the end of life.

Medical care at the end of life consumes 10% to 12% of the total health care budget. An

estimated 40% of the Medicare budget is spent during the last 30 days of life.39 Some have

posited that increased use of hospice and advance directives and lower use of high-technology

interventions for terminally ill patients will produce significant cost savings. However, the

studies on cost savings from hospice and advance directives are not definitive. The 3 randomized

trials of hospice and advance directives use show no overall savings, but the authors of a review

suggest that the studies were either too small for confidence in their negative results or their

intervention and cost accounting are flawed.40 In the absence of a definitive study, the existing

data suggest that hospice and advance directives can save between 25% and 40% of health care

costs during the last month of life, but far less (and perhaps nothing) in the 3-12 months before

death. Although, these savings are less than most people anticipate, they do indicate that hospice

and advance directives should be encouraged because they certainly do not cost more and they

provide a means for patients to exercise their autonomy over end-of-life decisions.40 Finally,

several of the promising interventions described above (eg, the POLST intervention), are

relatively inexpensive. For example, 500 POLST forms can be ordered from Oregon Health

Science University’s Web site41 for less than $100, although the cost of implementing the

POLST program is unknown.

Comment

Preventing unwanted aggressive care at the end of life requires active communication

between provider and patient, and effective strategies to transfer information regarding

preferences seamlessly across care venues. The dominant strategy to improve care in this area

over the past 20 years has been the promotion of advance directives. Although the enthusiasm

for advance directives has not been matched by evidence of their effectiveness, SUPPORT and

other studies have renewed public concern and prompted providers and policy makers to

reexamine advance care planning and strive to improve it. Although we have found evidence of

several potentially promising strategies (perhaps the most promising of which is the POLST

form), the inevitability of death and the importance patients place on improving end-of-life care

point strongly to the need for further research in this area.
564

Figure 49.1. POLST Wallet Card instructions

POLST WALLET CARD INSTRUCTIONS

 This is an identification wallet card for the Physician

Orders for Life-Sustaining Treatment (POLST) document. 

This card is not a substitute for a completed POLST

document. It provides a summary of the POLST document

and is expected to be honored by care providers.

 The POLST document and wallet card are completed by

the physician. The physician must sign both the POLST

document and the wallet card to make the wallet card valid.

Instructions continued on other side.

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Physician Orders for Life-Sustaining Treatment

Name: __________________________________________

Resuscitation (Patient has no pulse and is not breathing:

 • Resuscitate • Do Not Resuscitate (DNR)

Medical Interventions (has pulse and/or is breathing):

 • Comfort Measures Only • Limited Interventions

 • Advanced Interventions • Full Treatment/Resuscitation

Antibiotics:

 • No antibiotics except if needed for comfort

 • No invasive (IM/IV) antibiotics • Full Treatment

Instructions continued on other side.

...continued from other side

 It is recommended that the completed wallet card

 be laminated in plastic for durability and to

 prevent alteration. An existing card should be

 destroyed if the POLST document is changed. 

 A new wallet card can be completed to match

 the new physician orders.

 • • CENTER FOR ETHICS IN HEALTH CARE

 Oregon Health Sciences University

 3181 SW Sam Jackson Park Rd., UHN-86

 Portland, Oregon 97201-3098

 (503) 494-4466

_ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Artificially Administered Fluids and Nutrition:

 • No feeding tube/IV fluids • Full Treatment

 • No long term feeding tube/IV fluids

Discussed with:

 • Patient • Health Care Representative

 • Court-appointed Guardian • Spouse • Other

I have completed the following forms:

 • Advance Directive • Court-appointed Guardian

____________________________________ ________________

Print name of Physician Phone

____________________________________ ________________

Signature of Physician Datee

• • Center for Ethics in Health Care Developed in conformance with ORS 127.505 et seq.

Center for Ethics in Health Care. Reproduced with permission.
565

References

1. Jonsen AR SM, Winslade WJ. Clinical Ethics: A Practical Approach to Ethical Decisions

in Clinical Medicine. Fourth ed. New York, NY: McGraw-Hill; 1998.

2. Ethics manual. Fourth edition. American College of Physicians. Ann Intern Med. 1998;

128: 576-94.

3. Teno J, Lynn J, Wenger N, Phillips RS, Murphy DP, Connors AF, Jr., et al. Advance

directives for seriously ill hospitalized patients: effectiveness with the patient selfdetermination act and the SUPPORT intervention. SUPPORT Investigators. Study to

Understand Prognoses and Preferences for Outcomes and Risks of Treatment. J Am Geriatr

Soc. 1997; 45: 500-7.

4. anonymous. A controlled trial to improve care for seriously ill hospitalized patients. The

study to understand prognoses and preferences for outcomes and risks of treatments

(SUPPORT). The SUPPORT Principal Investigators [published erratum appears in JAMA

1996 Apr 24; 275: 1232]. JAMA 1995; 274: 1591-8.

5. Gamble ER, McDonald PJ, Lichstein PR. Knowledge, attitudes, and behavior of elderly

persons regarding living wills. Arch Intern Med. 1991; 151: 277-80.

6. Muldoon MF, Barger SD, Flory JD, Manuck SB. What are quality of life measurements

measuring? BMJ. 1998; 316: 542-5.

7. Hanson LC, Tulsky JA, Danis M. Can clinical interventions change care at the end of life?.

Ann Intern Med. 1997; 126: 381-8.

8. Morrison RS, Olson E, Mertz KR, Meier DE. The inaccessibility of advance directives on

transfer from ambulatory to acute care settings. JAMA. 1995; 274: 478-82.

9. Broadwell A, Boisaubin, EV, Dunn, JK, Engelhardt, HT. Advance directives on hospital

admission: a survey of patient attitudes. South Med J. 1993; 86: 165-8.

10. Teno JM, Licks S, Lynn J, Wenger N, Connors AF, Jr., Phillips RS, et al. Do advance

directives provide instructions that direct care? SUPPORT Investigators. Study to

Understand Prognoses and Preferences for Outcomes and Risks of Treatment. J Am Geriatr

Soc.1997; 45: 508-12.

11. Danis M, Southerland LI, Garrett JM, Smith JL, Hielema F, Pickard CG, et al. A

prospective study of advance directives for life-sustaining care. N Engl J Med. 1991; 324:

882-8.

12. Christakis N, Iwashyna TJ. Attitude and self-reported practice regarding prognostication in

a national sample of internists. Arch Intern Med. 1998; 158: 2389-95.

13. Lo B, McLeod GA, Saika G. Patient attitudes to discussing life-sustaining treatment. Arch

Intern Med. 1986; 146: 1613-5.

14. anonymous. Good care of the dying patient. Council on Scientific Affairs, American

Medical Association. JAMA. 1996; 275: 474-8.

15. Wenger NS, Phillips RS, Teno JM, Oye RK, Dawson NV, Liu H, et al. Physician

understanding of patient resuscitation preferences: insights and clinical implications. J Am

Geriatr Soc. 2000; 48: S44-51.

16. Covinsky KE, Fuller JD, Yaffe K, Johnston CB, Hamel MB, Lynn J, et al. Communication

and decision-making in seriously ill patients: findings of the SUPPORT project. The Study

to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am

Geriatr Soc. 2000; 48: S187-93.

17. Approaching Death: Improving Care at the End of Life. Washington DC: National

Academy Press; 1997.
566

18. Donaldson M, Field, MJ. Measuring quality of care at the End of Life. Arch Intern Med.

1998; 158: 121-28.

19. Ebell MH, Becker LA, Barry HC, Hagen M. Survival after in-hospital cardiopulmonary

resuscitation. A meta-analysis. J Gen Intern Med.1998; 13: 805-16.

20. Basta L, Plunkitt K, Shassy, R, Gamouras G. Cardiopulmonary resuscitation in the elderly:

Defining the limits of appropriateness. Am J Geriatr Cardiol. 1998; 7: 46-55.

21. Tolle SW, Tilden VP, Nelson CA, Dunn PM. A prospective study of the efficacy of the

physician order form for life-sustaining treatment. J Am Geriatr Soc. 1998; 46: 1097-102.

22. Jaret P. Leading Patients in End-of-Life Decisions. Hippocrates; 1999. p. 33-37.

23. Lee M, Brummel-Smith, K, Meyer, J, Drew, N, London, MR. Physician orders for lifesustaining treatment (POLST): outcomes in a PACE program. Program of All-Inclusive

Care for the Elderly. J Am Geriatr Soc. 2000; 48: 1219-25.

24. Dexter P, Wolinsky, FD, Gramelspacher, GP, Zhou, ZH, Eckert, GJ, Waisburd, M,

Tierney, WM. Effectiveness of computer-generated reminders for increasing discussions

about advance directives and completion of advance directive forms. A randomized,

controlled trial. Ann Intern Med. 1998; 128: 102-10.

25. Ghusn H, Teasdale, TA, Jordan, D. Continuity of do-not-resuscitation orders between

hospital and nursing home settings. J Am Geriatr Soc. 1997; 45: 465-69.

26. Tulsky JA, Fischer GS, Rose MR, Arnold RM. Opening the black box: how do physicians

communicate about advance directives?. Ann Intern Med. 1998; 129: 441-9.

27. Rabow M, Hardie, GE, Fair, JM, McPhee, SJ. End-of-life care content in 50 textbooks

from multiple specialties. JAMA. 2000; 283: 771-8.

28. McPhee S, Rabow, MW, Pantilat, SZ, Markowitz, AJ. Finding our way- - perspectives on

care at the close of life. JAMA. 2000; 284: 2512-13.

29. Emanuel LL, von Gunten, C.F., Ferris, F.D. The Education for Physicians on End-of-Life

Care (EPEC) Curriculum; 1999.

30. Larson DG, Tobin DR. End-of-life conversations: evolving practice and theory. JAMA.

2000; 284: 1573-8.

31. Lo B. Improving care near the end of life. Why is it so hard? [editorial; comment]. JAMA.

1995; 274: 1634-6.

32. Buckman R KY. How to Break Bad News: A Guide for Health Care Professionals.

Baltimore, MD: Johns Hopkins University Press; 1992.

33. Lo B, Quill T, Tulsky J. Discussing palliative care with patients. ACP-ASIM End-of-Life

Care Consensus Panel. American College of Physicians-American Society of Internal

Medicine. Ann Intern Med. 1999; 130: 744-9.

34. Pantilat SZ, Alpers A, Wachter RM. A new doctor in the house: ethical issues in hospitalist

systems. JAMA. 1999; 282: 171-4.

35. Auerbach AD, Pantilat SZ, Wachter RM, Goldman L. Processes and outcomes of end-oflife care in a voluntary hospitalist model. J Gen Intern Med. 2001; 16: 115.

36. Hammes BJ, Rooney BL. Death and end-of-life planning in one midwestern community.

Arch Intern Med. 1998; 158: 383-90.

37. Lynn J SJ, Kabcenell A. Beyond the Living Will: Advance Care Planning for All Stages of

Health and Disease. Improving Care for the End of Life: A Sourcebook for Health Care

Managers and Clinicians: Oxford University Press; 2000. p. 73-90.

38. Molloy DW, Guyatt GH, Russo R, Goeree R, O'Brien BJ, Bedard M, et al. Systematic

implementation of an advance directive program in nursing homes: a randomized

controlled trial. JAMA. 2000; 283: 1437-44.
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39. Kurent J. Death and Dying in America: The need to improve End-of-Life Care. Carolina

Healthcare Business 2000:16-19.

40. Emanuel EJ. Cost savings at the end of life. What do the data show? JAMA. 1996; 275:

1907-14.

41. Center for Ethics in Health Care, Oregon Health Sciences University,

http://www.ohsu.edu/ethics/polst.htm, last accessed May 8, 2001.
568
569

Chapter 50. Other Practices Related to Patient Participation

Laura T. Pizzi, PharmD

Neil I. Goldfarb

David B. Nash, MD, MBA

Thomas Jefferson University School of Medicine

and Office of Health Policy & Clinical Outcomes

Background

A number of practices and resources aim to facilitate the role of patients as their own

safety advocates. These practices are not intended to shift the burden of monitoring medical error

to patients. Rather, they encourage patients to share responsibility for their own safety. Although

these types of interventions hold promise for enhanced patient safety, there is yet insufficient

evidence of their effectiveness. Therefore, this chapter is a brief, general survey of practices

related to patient participation; there are few practices that have been studied with sufficient

rigor to merit a full evidence-based review. This chapter explicitly excludes consumer report

cards, since such tools presently are more relevant to health care quality than patient safety.1,2

There is a substantial literature on the patient’s role in quality improvement related to specific

diseases - eg, self-management and general education for patients with certain chronic diseases

such as asthma,3-5 diabetes,6-8 and rheumatoid arthritis,9-12 as well preoperative educational and

preparation programs for patients undergoing cardiac surgery. 13 This literature was not reviewed

in detail, both because it falls outside our definition of patient safety practices (Chapter 1) by

virtue of its disease specificity, and because the volume of material was overwhelming given the

time allocated for the production of this Report. There are obvious additional opportunities to

promote patient involvement in helping protect their own safety drawn from the disease-specific

experiences of the past, and this should be the subject of further exposition and analysis.

Patient Education Materials Regarding Patient Safety

Books, Web sites and consumer group publications abound with health care and medical

information for patients.14 The goal of these resources is to enable consumers to arm themselves

with the knowledge to protect themselves. Health care providers may wish to distribute such

materials to patients to alert them of the possible problem of medical error, and encourage those

that would like to take appropriate action.

The Agency for Healthcare Research and Quality15 produces a 5-page “Patient Fact

Sheet” on preventing medical errors. This fact sheet educates patients on the problem of medical

error, and provides 20 tips patients may follow to avoid medical error, ranging from properly

measuring liquid medications to ensuring health care employees have washed their hands.

Proprietary educational materials have also been developed. For instance, DoctorQuality,

Inc., a quality management company that provides products and services to health care

consumers, purchasers, and providers, has developed online and offline tools that providers and

patients can use to improve care,16 including patient safety workbooks and quality guides for a

variety of diagnoses and surgical procedures. The books describe the key events that patients

should anticipate at each step of diagnosis and treatment, identify high-risk points in the

treatment plan where mistakes are more likely occur,14 and provide tips as to how to avert

common errors.

 Patients may also find resources in the popular literature. In Lerner’s Consumer Guide to

Health Care, the authors coach readers on questions to ask their physicians and ways to avoid
570

medical mistakes.17 Dr. Robert Arnot's book, The Best Medicine,

18 educates patients about

specific procedures (eg, coronary artery bypass surgery, cesarean section, hysterectomy, and

carotid endarterectomy). Potential complications of each of these procedures are described, and

volumes, average lengths of stay, and complication rates of major hospitals are presented.

Health information on the Web has increased patients’ desire for medical information and

raised significant issues regarding patient safety and the manner in which patients approach their

doctors for information.19 A recent study revealed that many physicians believe that Web

resources can distance patients from physicians and have an adverse effect on patient safety.

Specifically, there is concern that patients can receive and believe misinformation, or read of

treatments and procedures unfamiliar to physicians, and in both instances lower their trust in

physician recommendations.20 Other physicians see the Web as a positive development in patient

safety because when patients approach their doctors prepared with questions, office visits run

more smoothly, and the physician’s counsel may be better received.20

Similar issues surround the topic of direct-to-consumer (DTC) marketing by

pharmaceutical companies.21 In 1997 the Food and Drug Administration relaxed restrictions on

television and advertising for prescription medication. Drug companies responded with an

explosion of marketing in all forms of media. DTC advertising may stimulate discussion

between patients and their doctors about treatment options, but it also drives patients to demand

newer and costlier medications, when less expensive treatments might be effective.22 When

doctors resist, 46% of patients try to persuade them to change the original recommendation and

another 24% attempt to obtain the requested drugs from another physician.22 These sort of

interactions erode the physician-patient relationship and may jeopardize safety by promoting

polypharmacy.

Practices to Improve Non-compliance

Compliance with medical advice is widely discussed in the literature and non-compliance

with treatment may result in adverse drug events.23 The frequency of non-compliance is higher

than many health care professionals realize.24 Non-compliance may arise from

misunderstandings regarding instructions for drug use, self-care, or other factors. In addition,

some of these misunderstandings may arise from remediable factors, such as language barriers25

or low health literacy.26,27 Simple solutions, such as using a trained interpreter instead of a family

member or untrained volunteer, and providing self-care and other literature in multiple languages

and bilingual versions may improve patient understanding. Other interventions, such as patient

education publications, have been proposed to reduce adverse drug events due to noncompliance.28

Access to Medical Records

Although patient access to their own medical records is regulated in some states, these

statutes differ across the United States.29 Some states mandate certain levels of access for

patients; others limit access or allow the provider to deem access appropriate or inappropriate.

Other countries, such as Britain, have passed legislation requiring that providers allow patients to

have complete access to their medical records.30 Some argue that access to medical records may

encourage patients to take a more active role in their own health care, allow patients to become

better informed about their care, and increase rapport. Others argue that staff may modify

medical records due to concerns about offending the patient, and will be diverted by the time

needed to explain information contained in the records. Finally, still others express concern that

patients may be unnecessarily worried by what they read.30 No studies in the United States have
571

analyzed these competing views, and therefore it is not clear whether cultural norms reported in

studies from other countries are applicable here, and whether allowing patients to review their

own charts will have the intended effect of reducing errors.

Comment

With the growing level of consumerism in health care,31 patients may wish to take a more

active role in reducing their chance of experiencing a medical error. However, the research

regarding the ways in which providers can facilitate this role for patients who desire it is lacking.

More research is needed on the efficacy of these interventions regarding medical error reduction

and on patients’ willingness and ability to use them.

References

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health care. Do they make a difference in patient care? JAMA. 1997; 278: 1579-1584.

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data: what do we expect to gain? A review of the evidence JAMA. 2000; 283: 1866-1874.

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6. Fain JA, Nettles A, Funnell MM, Charron D. Diabetes patient education research: an

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7. Norris SL, Engelgau MM, Narayan KM. Effectiveness of self-management training in type

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systematic review. Health Technol Assess. 2001; 5: 1-79.

9. Superio-Cabuslay E, Ward MM, Lorig KR. Patient education interventions in osteoarthritis

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drug treatment. Arthritis Care Res. 1996; 9: 292-301.

10. Brus H, van de Laar M, Taal E, Rasker J, Wiegman O. Compliance in rheumatoid arthritis

and the role of formal patient education. Semin Arthritis Rheum. 1997; 26: 702-710.

11. Brus HL, van de Laar MA, Taal E, Rasker JJ, Wiegman O. Effects of patient education on

compliance with basic treatment regimens and health in recent onset active rheumatoid

arthritis. Ann Rheum Dis. 1998; 57: 146-151.

12. Barlow JH, Turner AP, Wright CC. A randomized controlled study of the Arthritis SelfManagement Programme in the UK. Health Educ Res. 2000; 15: 665-680.

13. Arthur HM, Daniels C, McKelvie R, Hirsh J, Rush B. Effect of a preoperative intervention

on preoperative and postoperative outcomes in low-risk patients awaiting elective coronary

artery bypass graft surgery. A randomized, controlled trial. Ann Intern Med. 2000; 133:

253-262.
572

14. Robinson JL, Nash DB. Consumers' role in patient safety. QRC Advis. 2000; 17: 1-3.

15. Patient Fact Sheet. 20 Tips to Help Prevent Medical Errors (AHRQ Publication No. 00-

PO38) Agency for Healthcare Research and Quality. Available at:

http://www.ahrq.gov/consumer/20tips.htm. Accessed June 25, 2001.

16. DoctorQuality corporate website DoctorQuality.com, Inc. Available at:

http://www.doctorquality.com/www/about.asp. Accessed June 25, 2001.

17. Lerner P, Lerner J. Lerner's consumer guide to health care: how to get the best health care

for less. Seattle, WA: Lerner Communications; 2001.

18. Arnot RB. The Best Medicine: How to Choose the Top Doctors, the Top Hospitals, and the

Top Treatments. Reading, MA: Addison-Wesley Publishing Company; 1993.

19. Fotch E. The effect of the world wide web on you and your patients. Ophthalmol Clin

North Am. 2000; 13: 261-269.

20. Bard M. How will the web affect the physician-patient relationship? Interview by Marilynn

Larkin. Lancet. 2000; 356: 1777.

21. Wilkes MS, Bell RA, Kravitz RL. Direct-to-consumer prescription drug advertising: trends,

impact, and implications. Health Aff (Millwood). 2000; 19: 110-128.

22. Brown AB. The direct-to-consumer advertising dilemma. Patient Care 2001; 35:22-33.

2001; 35: 22-33.

23. Holt GA, Dorcheus L, Hall EL, Beck D, Ellis E, Hough J. Patient interpretation of label

instructions. Am Pharm. 1992; NS32: 58-62.

24. Fletcher RH. Patient compliance with therapeutic advice: a modern view. Mt Sinai J Med.

1989; 56: 453-458.

25. Woloshin S, Bickell NA, Schwartz LM, Gany F, Welch HG. Language barriers in medicine

in the United States. JAMA. 1995; 273: 724-728.

26. Williams MV, Parker RM, Baker DW, Parikh NS, Pitkin K, Coates WC, et al. Inadequate

functional health literacy among patients at two public hospitals. JAMA. 1995; 274: 1677-

1682.

27. Gazmararian JA, Baker DW, Williams MV, Parker RM, Scott TL, Green DC, et al. Health

literacy among Medicare enrollees in a managed care organization. JAMA. 1999; 281: 545-

551.

28. Medication safety issue brief. Asking consumers for help. Part 3. Hosp Health Netw. 2001;

75: suppl 2 p. following 56.

29. Patient Confidentiality American Medical Association. Available at: http://www.amaassn.org/ama/pub/category/4610.html. Accessed June 25, 2001.

30. Grange A, Renvoize E, Pinder J. Patients' rights to access their healthcare records. Nurs

Stand. 1998; 13: 41-42.

31. Nash DB, Manfredi MP, Bozarth B, Howell S. Connecting with the new healthcare

consumer. Gaithersburg, MD: Aspen Publishers, Inc.; 2001.
573

PART IV. PROMOTING AND IMPLEMENTING SAFETY PRACTICES

Chapter 51. Practice Guidelines

Chapter 52. Critical Pathways

Chapter 53. Clinical Decision Support Systems

Chapter 54. Educational Techniques Used in Changing Provider Behavior

Chapter 55. Legislation, Accreditation, and Market-Driven and Other Approaches to

Improving Patient Safety
574
575

Chapter 51. Practice Guidelines

Robert Trowbridge, MD

University of California, San Francisco School of Medicine

Scott Weingarten, MD, MPH

University of California, Los Angeles School of Medicine

Background

Practice guidelines are among the most widely employed methods of modifying

physician behavior. Defined as “systematically developed statements to assist practitioner and

patient decisions about appropriate health care for specific clinical conditions,”

1

 guidelines may

affect both the process and the outcome of care. Although guideline development and

implementation have traditionally focused on ensuring a perceived standard of care, increasing

emphasis has been placed on patient outcomes and patient safety. In this regard, thousands of

guidelines have been promulgated on a great variety of clinical topics ranging from the

prevention of falls in the elderly to the proper use of bone marrow transplantation.2,3

Practice Description

Guidelines vary greatly in terms of both method of development and format. Some

consist of relatively straightforward statements that advocate a particular clinical practice,

whereas others represent a series of complex algorithms that require the input of multiple clinical

variables. Many guidelines are developed by specialty and advocacy organizations with attention

paid to rigorously conducted systematic reviews.4

 Others may simply reflect a local standard of

care.

Guidelines should only be considered a potential source of information and are effective

at modifying physician behavior only when coupled with appropriate implementation strategies.

Guidelines disseminated using a multifaceted approach that provides for peer influence and

management support, for example, are more likely to be successful in influencing provider

behavior than strategies that depend solely on the passive dissemination of printed materials.5

Prevalence and Severity of Target Safety Problem/Opportunities for Impact

Practice guidelines have the potential to greatly impact patient safety as they may

facilitate widespread dissemination of practices that effectively reduce medical errors. It is well

established in other medical fields that known tenets of effective health care are not practiced on

a universal basis despite overwhelming evidence supporting their use. According to an audit of

Medicaid charts in Connecticut, for example, only 50% of patients presenting with an acute

myocardial infarction received aspirin and beta-blockers on the day of admission despite

substantial evidence that these practices reduce mortality.6

 A second report estimated that 3500

infarctions would be averted and 4300 lives saved annually if beta-blockers were appropriately

prescribed in patients with coronary artery disease.7

 Guidelines could help rectify similar

shortcomings in the field of patient safety with corresponding reductions in medical errors.
576

Study Design

There are no well-designed studies that specifically evaluate the effect of practice

guidelines on patient safety. However, research regarding their effectiveness in modifying

physician behavior and improving patient outcomes is plentiful. The most comprehensive review

evaluating general utility of guidelines involved an extensive search of MEDLINE and other

electronic databases, the gray literature and the bibliographies of pertinent articles. Its analysis

included 59 reports consisting of both controlled time series and before-after studies in addition

to randomized trials.8

A second systematic review, limited to computer-based guidelines, reported the results of

a search of several electronic databases (MEDLINE and CINAHL) complemented by a limited

bibliography search. It included 25 studies detailing the use of 20 guideline systems. In this

group, there were 10 time series studies (all without external controls) and 10 controlled trials, 9

of which were randomized.9

A final systematic review, limited to the primary care setting, also searched MEDLINE

and several other electronic databases and included a limited bibliography search.10 This review

included only randomized trials that reported clinical outcomes associated with the treatment of

patients with established diagnoses and identified 13 studies for inclusion. In keeping with these

criteria, trials of the use of guidelines to promote preventive health care and proper diagnostic

evaluations were excluded.

Several studies not represented in the above systematic reviews also provide valuable

information on the effectiveness of practice guidelines. Two multicenter studies, for example,

evaluated the impact of guidelines on the treatment of patients admitted for pneumonia and

certain surgical procedures, respectively. Both of these were prospective before-after trials.11,12 A

prospective controlled trial of the implementation of a diabetes guideline using problem-based

learning was also completed,13 as were 2 randomized controlled trials of the local

implementation of nationally developed guidelines.14,15 Other recently completed works include

an evaluation of a guideline for the outpatient treatment of cystitis with concurrent and historical

controls, and a prospective before- after investigation of a guideline for the treatment of upper

gastrointestinal hemorrhage.16,17

Study Outcomes

Very few of the reviewed studies report outcomes specifically linked to patient safety.

Those that do (such as guidelines to prevent falls in the elderly (Chapter 26) and to promote hand

washing (Chapter 12)) are of less than robust design.2,18,23 A few of the studies included in the

systematic reviews do report the effect of guidelines on surgical site infections and vaccination

rates, but results are reported in terms of the process of care rather than the outcome of care. The

systematic review from Worrall et al is an exception, as it only analyzed studies that reported

direct clinical variables.10 Among the other studies, however, the most commonly reported

variables were length of stay, rates of provider adherence to guidelines, complication rates and

the rates of the appropriate use of diagnostic testing.
577

Evidence for Effectiveness of Practice

Despite the inherent methodologic problems of many of the cited studies, there is

substantial evidence that practice guidelines may be effective in influencing provider behavior

and patient outcomes. In the seminal review from Grimshaw and Russell, 9 of 11 studies

reporting clinical outcomes noted some degree of improvement while the process of care was

found to improve in 55 of 59 studies.8

 This review did include several trials with marginal study

design, but the authors argued for the inclusion of the time series and before-after studies on the

premise that the magnitude of effect seen in many of the studies overwhelmed any potential bias

that may have been attributable to study design. They additionally noted that the randomized

trial may not represent the best method for evaluating practice guidelines.

The systematic review investigating the utility of computer-based guidelines is similarly

encouraging.9

 Fourteen of 18 studies found guidelines increased provider adherence to the tenets

of care promoted by the guidelines. Of the 8 studies that evaluated patient outcomes, 3 found

improvements. These results mirror those of Grimshaw and Russell and reinforce the supposition

that guidelines, at least in the studies completed to date, are more effective at influencing the

process rather than the outcome of care.

The systematic review of controlled trials reporting clinical outcomes in the primary care

setting is significantly less optimistic.10 Only 5 of the 13 trials analyzed showed improvements in

the defined clinical outcomes. None did so across all of the study groups or for an extended

period of time. These results cast doubt on the utility of guidelines, particularly since this paper

only included rigorously conducted trials reporting clinical outcomes, in contrast to the larger

review by Grimshaw and Russell. However the authors correctly assert that many of these

studies likely used guidelines that were not evidence-based and which may not have been

sensitive enough to discern small improvements in clinical outcomes. In addition, it is likely that

improvements in the process of care represents a reasonable surrogate endpoint for clinical

outcomes given the size of the studies that would need to be conducted to show a beneficial

outcomes effect of guidelines. To exclude all studies using this surrogate endpoint may be an

extreme and unnecessary measure.

The studies of guidelines that have been published since the completion of the above

systematic reviews are similarly conflicting. The multicenter study of the pneumonia guideline,

for example, showed no effect on the length of stay or complication rates whereas the study of

the postoperative surgical guidelines showed a significant decrease in the length of stay in 2 of

the 3 groups.11,12 Additionally, studies of the implementation of nationally developed guidelines

yielded conflicting results, perhaps as a function of the implementation strategies used in each

study. The study of the Agency for Healthcare Policy and Research (AHCPR, now the Agency

for Healthcare Research and Quality, AHRQ) guideline for cessation of smoking in pregnant

woman, which was a rigorously conducted randomized controlled trial, used extensive

implementation strategies and showed a marked and statistically significant increase in the

smoking cessation rate in the intervention group.15 In contrast, the trial using continuous quality

improvement measures and academic detailing to promote the AHCPR depression guideline

showed little effect.14 Yet several other studies, all of reasonable design and well-controlled,

demonstrated improvements in the process of care13,16,17 with one also reporting a marked

clinical benefit in improving glycemic control in diabetics.13
578

Potential for Harm

It has been theorized that practice guidelines, if improperly developed or implemented,

could actually be detrimental to the process of care or worsen clinical outcomes. A study of

guidelines in the use of neurodiagnostic testing in patients with low back pain found the tests

were more frequently utilized in an improper fashion than at baseline when clinicians were given

a set of guidelines that were relatively narrow in focus.19 Another study of patients treated for

congestive heart failure found the guidelines actually increased the length of stay beyond that

which was clinically necessary.20 Although neither of these studies revealed worsened patient

outcomes due to the guidelines, that potential certainly exists. In addition, the promulgation of

guidelines with imprudent advice could also result in widespread harm to patients.

Costs and Implementation

Developing and implementing practice guidelines is expensive. When developed for a

complex clinical problem by a national organization, for example, they consume tremendous

resources, often tens of thousands of dollars.21 In addition, some of the more successful

implementation strategies, such as academic detailing (Chapter 54), also require a substantial

measure of effort and financial outlay.

The manner in which practice guidelines are implemented is at least as important as the

content of the guidelines themselves. Several systematic reviews have investigated both the

strategies that are associated with successful institution of guidelines and the specific barriers to

implementation.5, 22, 23 These reviews concluded that the deterrents vary by practice location and

that strategies to circumvent these barriers must be devised on an individual and local basis. In

general, however, the number and intensity of the implementation strategies employed generally

corresponds with the ultimate success of the guideline.

Comment

There is convincing but by no means overwhelming evidence that practice guidelines are

effective in positively influencing the process and, to a lesser extent, the outcome of care. Many

of the completed studies are plagued by methodologic shortcomings that reflect the difficulty

inherent in studying the impact of guidelines. Although evidence specific to the use of guidelines

in patient safety is scanty, they are likely to be as effective in this area as any other. It thus

appears that well-constructed guidelines could play a significant role in ensuring patient safety

and reducing medical errors. The effectiveness of guidelines, however, is dependent on many

factors outside of their content. In particular, specific attention must be focused on utilizing

appropriate implementation strategies if the full potential of guidelines is to be realized.

References

1. Field MJ LK, eds. Clinical Practice Guidelines: Directions for a new program.

Washington, DC: National Academy Press; 1990.

2. Baraff LJ, Lee TJ, Kader S, Della Penna R. Effect of a practice guideline for emergency

department care of falls in elder patients on subsequent falls and hospitalizations for

injuries. Acad Emerg Med. 1999; 6:1224-31.

3. Rowe JM, Ciobanu N, Ascensao J, Stadtmauer EA, Weiner RS, Schenkein DP, et al.

Recommended guidelines for the management of autologous and allogeneic bone marrow

transplantation. A report from the Eastern Cooperative Oncology Group (ECOG). Ann

Intern Med. 1994; 120: 143-58.
579

4. Weingarten S. Using practice guideline compendiums to provide better preventive care.

Ann Intern Med. 1999; 130: 454-8.

5. Wensing M, van der Weijden T, Grol R. Implementing guidelines and innovations in

general practice: which interventions are effective? Br J Gen Pract. 1998; 48: 991-7.

6. Holmboe ES, Meehan TP, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Use of

critical pathways to improve the care of patients with acute myocardial infarction. Am J

Med. 1999; 107: 324-31.

7. Phillips KA, Shlipak MG, Coxson P, Goldman L, Heidenreich PA, Weinstein MC, et al.

Underuse of beta-blockers following myocardial infarction. JAMA. 2001; 285: 1013.

8. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic

review of rigorous evaluations. Lancet. 1993; 342: 1317-22.

9. Shiffman RN, Liaw Y, Brandt CA, Corb GJ. Computer-based guideline implementation

systems: a systematic review of functionality and effectiveness. J Am Med Inform Assoc.

1999; 6: 104-14.

10. Worrall G, Chaulk P, Freake D. The effects of clinical practice guidelines on patient

outcomes in primary care: a systematic review. CMAJ. 1997; 156: 1705-12.

11. Weingarten S, Riedinger MS, Sandhu M, Bowers C, Ellrodt AG, Nunn C, et al. Can

practice guidelines safely reduce hospital length of stay? Results from a multicenter

interventional study. Am J Med. 1998; 105: 33-40.

12. Rhew DC, Riedinger MS, Sandhu M, Bowers C, Greengold N, Weingarten SR. A

prospective, multicenter study of a pneumonia practice guideline. Chest. 1998; 114: 115-9.

13. Benjamin EM, Schneider MS, Hinchey KT. Implementing practice guidelines for diabetes

care using problem-based learning. A prospective controlled trial using firm systems.

Diabetes Care. 1999; 22: 1672-8.

14. Brown JB, Shye D, McFarland BH, Nichols GA, Mullooly JP, Johnson RE. Controlled

trials of CQI and academic detailing to implement a clinical practice guideline for

depression. Jt Comm J Qual Improv. 2000; 26: 39-54.

15. Windsor RA, Woodby LL, Miller TM, Hardin JM, Crawford MA, DiClemente CC.

Effectiveness of Agency for Health Care Policy and Research clinical practice guideline

and patient education methods for pregnant smokers in medicaid maternity care. Am J

Obstet Gynecol. 2000; 182: 68-75.

16. Saint S, Scholes D, Fihn SD, Farrell RG, Stamm WE. The effectiveness of a clinical

practice guideline for the management of presumed uncomplicated urinary tract infection

in women. Am J Med. 1999; 106: 636-41.

17. Hay JA ML, Weingarten SR, Ellrodt AG. Prospective evaluation of a clinical guideline

recommending hospital length of stay in upper gastrointestinal tract hemorrhage. JAMA.

1997: 2151-6.

18. Baraff LJ, Lee TJ, Kader S, Della Penna R. Effect of a practice guideline on the process of

emergency department care of falls in elder patients. Acad Emerg Med. 1999; 6: 1216-23.

19. Shekelle PG, Kravitz RL, Beart J, Marger M, Wang M, Lee M. Are nonspecific practice

guidelines potentially harmful? A randomized comparison of the effect of nonspecific

versus specific guidelines on physician decision making. Health Serv Res. 2000; 34: 1429-

48.

20. Weingarten S, Riedinger M, Conner L, Johnson B, Ellrodt AG. Reducing lengths of stay in

the coronary care unit with a practice guideline for patients with congestive heart failure.

Insights from a controlled clinical trial. Med Care. 1994; 32: 1232-43.
580

21. Smith WR. Evidence for the effectiveness of techniques to change physician behavior.

Chest. 2000; 118: 8S-17S.

22. Davis DA, Taylor-Vaisey A. Translating guidelines into practice. A systematic review of

theoretic concepts, practical experience and research evidence in the adoption of clinical

practice guidelines. CMAJ. 1997; 157: 408-16.

23. Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, et al. Why don't

physicians follow clinical practice guidelines? A framework for improvement. JAMA.

1999; 282: 1458-65.
581

Chapter 52. Critical Pathways

Robert Trowbridge, MD

University of California, San Francisco School of Medicine

Scott Weingarten, MD, MPH

University of California, Los Angeles School of Medicine

Background

Burgeoning concerns regarding patient safety, variable health care quality and increasing

health care costs have led to the introduction of clinical management tools that have their origins

outside of the traditional health care sector. Primary among these innovations has been the

implementation of critical pathways, administrative models that streamline work and production

processes.1

 Critical pathways have been utilized extensively in several different business sectors

including the construction and automotives industries.2-4 It is theorized that the adaptation of

pathways to health care, particularly inpatient care, may help ensure the delivery of quality care

and decrease the occurrence of medical errors.

Practice Description

Although closely related to clinical practice guidelines (Chapter 51), pathways more

directly target the specific process and sequence of care, frequently plotting out the expected

course of an illness or procedure with associated prompts for appropriate interventions. Also

known as clinical pathways and care maps, pathways are generally multidisciplinary by design

and may incorporate the responsibilities of physicians and nurses with those of ancillary medical

providers including pharmacists, physical therapists and social workers.5

 They are regularly

intercalated into the point-of-care and may, in some cases, incorporate or even replace traditional

chart documentation. In addition, pathways are often evidence-based and may even be integrated

with locally or nationally developed clinical practice guidelines. Most pathways, however, are

locally developed and are most frequently implemented at the level of the hospital or medical

center as part of a cost-containment or quality assurance initiative.

Prevalence and Severity of the Problem/Opportunities for Impact

It is well established that the methods currently used to disseminate medical information

are both cumbersome and inefficient. Even medical advances that are well entrenched in the

literature and of unquestionable value are not routinely or universally implemented. A study of

patients treated for myocardial infarction in Connecticut, for example, revealed only 50% of

patients received the most basic beneficial treatments (aspirin and beta-blockers) at the time of

admission.6

 A second report suggested that 3500 myocardial infarctions would be averted and

4300 lives would be saved annually if all eligible patients with coronary artery disease were

prescribed beta-blockers.7

 Critical pathways, if able to beneficially alter health care provider

performance and ensure that effective patient safety strategies were practiced on a widespread

basis, could be powerful agents in the prevention of medical errors, in addition to any beneficial

impact they might have on overall health care quality.
582

Study Design

There is a dearth of well-designed studies analyzing the extent to which critical pathways

change physician behavior and patient outcomes. Even fewer relate specifically to the topic of

patient safety. There are no systematic reviews of pathways and most of the published work

describes the non-randomized implementation of pathways in which it is often difficult to

differentiate effects of the pathway from secular trends. The vast majority of these studies

describe the implementation of a pathway for a specific surgical procedure and use historical

controls with a retrospective before-after study design.8-19

Four randomized controlled trials investigated the impact of the implementation of

pathways.20-23 There are also several studies with non-randomized concurrent controls with

enrollment in the intervention arms being completed at the request of the attending physician.24,25

The latter group of studies also included historical control groups. There is one prospective

before-after trial in which the control group actually shifted to receive the intervention after a

washout period.26 Finally one study used historical controls and concurrent controls from other

hospitals in the region.27 Table 52.1 describes the salient features of these papers.

Study Outcomes

The great majority of the cited studies reported at least one clinical outcome (Level 1)

with the most commonly reported variable being diagnosis-related complications. Very few of

the studies reported more definitive endpoints, such as mortality. Most of the included studies

reported surrogate clinical end-points (Level 2) as the major study outcome variables, usually

length of stay and re-admission rates. The relative utilization of certain interventions including

medications, laboratory tests and radiology studies was also commonly reported. In addition,

most of the studies also included an analysis of the changes in costs associated with instituting

the pathway. Some of the studied pathways did include other recommendations for interventions

germane to the field of patient safety, including the use of indwelling urinary catheters (Chapter

15) and prophylactic preoperative antibiotics (Chapter 20.1), but these outcomes were rarely

reported.

Evidence for Effectiveness of the Practice

Several of the randomized controlled trials provide at least some evidence that critical

pathways can be effective in influencing health care provider behavior. One study evaluated the

effectiveness of a pathway for the treatment of asthma in children admitted to a non-ICU

hospital setting.22 Those patients treated under the pathway, when compared to the control group

undergoing “usual care,” had a shorter length of stay as well as decreased hospital charges and

medication usage, but no change in complication rates. Although the results are somewhat

promising, the study was likely skewed by a significant Hawthorne effect, as patients treated

under the pathway were placed on a separate clinical ward than those undergoing usual care

(although the same physicians cared for both groups of patients). This study found no impact on

the rate of complications, which provides little encouragement regarding the ability of pathways

to reduce medical errors and enhance patient safety.

A second randomized trial investigated the utility of a pathway for the treatment of

patients undergoing knee and hip replacement at an academic medical center in Australia.21

Implementation of the pathway was followed by significant decreases in the length of stay and

shorter times to patient mobilization and ambulation. More importantly, it showed a decrease in

the incidence of medical complications, including readmission rates (although this change did
583

not reach statistical significance). The study, although fairly small at 163 total patients,

represents some of the most convincing evidence that pathways may be effective in decreasing

complications.

A third randomized trial, performed by the same Australian group, evaluated the effect of

a pathway for the treatment of patients with hip fracture.20 Implementation of this pathway,

which provided recommendations regarding medications, laboratory and radiology testing and

discharge planning, resulted in a significantly shorter lengths of stay without any concomitant

change in complication rates. The study was rigorously conducted and complication rates were

meticulously documented, but no information regarding the effort needed from clinicians to

comply with the pathway was presented.

A final trial used cluster randomization to investigate the effectiveness of a critical

pathway for the treatment of community-acquired pneumonia in 19 Canadian hospitals.23 The

pathway, which was initiated upon presentation of the patient to the emergency department,

included recommendations for the use of a specific antibiotic and provided a clinical prediction

tool to aid in decisions regarding hospital admission. Following admission, a study nurse also

regularly placed guideline-based recommendations in the chart regarding changing to oral

antibiotic therapy and discharge planning. The pathway showed impressive results in terms of

cost containment, with a shorter length of stay and a smaller percentage of inappropriate

admissions. However, there were no significant changes in the clinical parameters measured,

including mortality and complication rates. In addition, it is difficult to dissect the effect of the

pathway from that of the other elements of the multifaceted intervention.

The second strata of studies were less encouraging. A prospective before-after evaluation

of the implementation of a pathway for the administration of supplemental oxygen for

hospitalized patients showed the pathway was associated with markedly elevated costs without

any significant clinical benefit.26 This study, which used an intensive 3-tiered strategy including

an oxygen order form, the posting of the pathway in patient rooms and a research nurse

providing immediate audit and feedback, doubled the cost of providing supplemental oxygen.

Although it did change some of the physician prescription practices, this alteration in practice

resulted in no appreciable clinical effect.

At least 2 other studies compared an intervention group with a non-randomized

concurrent control group (thus introducing the possibility of selection bias) as well as to

historical controls. In a study evaluating the impact of a critical pathway on the treatment of

patients undergoing neck dissection, the length of stay and total costs were significantly lower

for the pathway group when compared with those of the historical controls. However, the

differences disappeared when the concurrent control group was used.25 In the other, a study of a

pathway for the treatment of asthma exacerbations, the pathway resulted in improvements in

resource utilization that were significant compared to both historical and concurrent controls.24

However no changes were noted between the groups in readmission rates or medical outcomes.

Finally, there are a great number of observational before-after studies of pathways, the

vast majority of which relate to specific surgical procedures.8-19 Few of these studies account for

secular trends and their capacity for judging the effectiveness of critical pathways is limited, at

best. In addition, a recent evaluation of pathways for patients undergoing a variety of surgical

procedures compared the intervention group to both historical controls and to patients from

similar hospitals in the same region in an attempt to correct for such secular trends. Although

implementation of the pathways resulted in significant decreases in length of stay when

compared to the historical controls, these differences disappeared when the pathway groups were

compared to the concurrent control groups from the other hospitals.27 An additional study of the
584

effect of a pathway on the treatment of acute myocardial infarction demonstrated that the

improvements seen in the intervention group were likely secondary to secular trends and not an

independent effect of the pathway.6

 These powerful results cast a great deal of doubt over those

studies that demonstrated effectiveness of the pathways in comparison to historical controls

alone.

Potential for Harm

There are theoretical concerns that pathways may result in adverse patient outcomes as a

result of shortened length of stay and a dependence on “cookbook medicine,” although there is

little support for this in the literature.

Costs and Implementation

Although many studies report cost savings associated with instituting pathways, very few

detail the costs of developing and implementing them. One report attempted to put a dollar figure

on the development of a pathway for the treatment of patients undergoing knee replacement

surgery; however the reported estimate ($21,000) did not account for the time staff physicians

spent on the project.14 The expense of developing critical pathways in terms of physician time

commitment and actual financial outlay is unknown. In addition, most pathways are developed

on the local level and require a great deal of initiative and expertise on the part of the hospital or

medical center. Whether most centers have access to these resources is unclear.

Physicians and other providers are also not universally welcoming of critical pathways.

They are considered intrusive by some providers and evidence of “cookbook medicine” by

others. The developers of pathways must be careful to allow for clinical judgment and flexibility

in the pathways or they are likely to be ignored or applied too rigidly.

Comment

There is conflicting evidence regarding the efficacy of critical pathways as a method to

modify health care provider behavior and a means of implementing patient safety initiatives.

Although a few studies suggest they may impact physician practice and, to a lesser extent,

complication rates and other clinical outcomes, the data are inconsistent and more studies are

needed. Additionally it is unclear whether the costly development and implementation of

pathways represents an appropriate use of limited health care resources. Finally, there is very

little information on the application of pathways to patient safety.
585

Table 52.1. Key features of studies of critical pathways

Study Setting Design,

Outcomes

Clinical Outcomes

(p value)

Non-Clinical

Outcomes (p value)

Children with an asthma

exacerbation admitted to an

academic medical center: patients

randomized to pathway group or

usual care group22

Level 1,

Level 1

Shorter duration of

intensive nebulizer

treatment (0.02), length

of stay (0.01)

Lower room charges

(0.001) and therapy

charges (0.001)

Patients undergoing hip or knee

replacement surgery at an academic

medical center in Australia: patients

randomized to pathway group or

usual care group21

Level 1,

Level 1

Shorter length of stay

(0.011) and time to

mobilization (0.001) and

ambulation (0.02)

Patients being treated for hip fracture

at an academic medical center in

Australia20

Level 1,

Level 2

Shorter length of stay

(0.03)

Patients presenting to the emergency

department with pneumonia at 19

medical centers across Canada:

hospitals were randomized to

pathway group or usual care group23

Level 1,

Level 1

Lower rates of bed-days

per patient (0.04),

shorter length of stay

(0.01) and shorter

duration of IV therapy

(0.01)

Patients in need of supplemental

oxygen therapy: prospective beforeafter analysis with washout period26

Level 2,

Level 1

More frequent

appropriate oxygen

discontinuation orders

(0.001)

Increased costs (0.02)

Patients undergoing unilateral neck

dissection at an academic medical

center: pathway group compared to

historical controls and nonrandomized concurrent controls25

Level 2,

Level 1

Length of stay decreased

compared to historical

controls (0.001) but not

concurrent controls

Total costs decreased

compared to historical

controls (0.001) but

not concurrent

controls

Patients admitted to a community

teaching hospital for the treatment of

an asthma exacerbation: pathway

group compared to historical controls

and non-randomized concurrent

controls24

Level 2,

Level 1

More appropriate

antibiotic use and

conversion to nebulizer

treatment (0.002 for

historical controls, 0.05

for concurrent controls)

Patients undergoing one of several

defined surgical procedures over a

seven year period at an academic

medical center: pathway group

compared to historical controls as

well as to patients from other similar

hospitals in the same region27

Level 2,

Level 2

Decreased lengths of

stay for the pathway

group compared to the

historical controls, but

not compared to the

concurrent control group
586

References

1. Every NR, Hochman J, Becker R, Kopecky S, Cannon CP. Critical pathways : a review.

Committee on Acute Cardiac Care, Council on Clinical Cardiology, American Heart

Association. Circulation. 2000; 101: 461-5.

2. Critical Path Software Smoothes Road for Automotive Supplier. Industrial Engineering.

1992; 24: 28-29.

3. Kallo G. The reliability of critical path method (CPM) techniques in the analysis and

evaluation of delay claims. Cost Engineering. 1996; 38: 35-37.

4. Hatfield MN, J. The case for critical path. Cost Engineering. 1998; 40: 17-18.

5. Pearson SD, Goulart-Fisher D, Lee TH. Critical pathways as a strategy for improving care:

problems and potential. Ann Intern Med. 1995; 123: 941-8.

6. Holmboe ES, Meehan TP, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Use of

critical pathways to improve the care of patients with acute myocardial infarction. Am J

Med. 1999; 107: 324-31.

7. Phillips KA, Shlipak MG, Coxson P, Goldman L, Heidenreich PA, Weinstein MC, et al.

Underuse of beta-blockers following myocardial infarction. JAMA. 2001; 285: 1013.

8. Bradshaw BG, Liu SS, Thirlby RC. Standardized perioperative care protocols and reduced

length of stay after colon surgery. J Am Coll Surg. 1998; 186: 501-6.

9. Dardik A, Williams GM, Minken SL, Perler BA. Impact of a critical pathway on the results

of carotid endarterectomy in a tertiary care university hospital: effect of methods on

outcome. J Vasc Surg. 1997; 26: 186-92.

10. Firilas AM, Higginbotham PH, Johnson DD, Jackson RJ, Wagner CW, Smith SD. A new

economic benchmark for surgical treatment of appendicitis. Am Surg. 1999; 65: 769-73.

11. Hanna E, Schultz S, Doctor D, Vural E, Stern S, Suen J. Development and implementation

of a clinical pathway for patients undergoing total laryngectomy: impact on cost and

quality of care. Arch Otolaryngol Head Neck Surg. 1999; 125: 1247-51.

12. Leibman BD, Dillioglugil O, Abbas F, Tanli S, Kattan MW, Scardino PT. Impact of a

clinical pathway for radical retropubic prostatectomy. Urology. 1998; 52: 94-9.

13. Mabrey JD, Toohey JS, Armstrong DA, Lavery L, Wammack LA. Clinical pathway

management of total knee arthroplasty. Clin Orthop. 1997; 113: 125-33.

14. Macario A, Horne M, Goodman S, Vitez T, Dexter F, Heinen R, et al. The effect of a

perioperative clinical pathway for knee replacement surgery on hospital costs. Anesth

Analg. 1998; 86: 978-84.

15. March LM, Cameron ID, Cumming RG, Chamberlain AC, Schwarz JM, Brnabic AJ, et al.

Mortality and morbidity after hip fracture: can evidence based clinical pathways make a

difference? J Rheumatol. 2000; 27: 2227-31.

16. Noedel NR, Osterloh JF, Brannan JA, Haselhorst MM, Ramage LJ, Lambrechts D. Critical

pathways as an effective tool to reduce cardiac transplantation hospitalization and charges.

J Transpl Coord. 1996; 6: 14-9.

17. Rumble SJ, Jernigan MH, Rudisill PT. Determining the effectiveness of critical pathways

for coronary artery bypass graft patients: retrospective comparison of readmission rates. J

Nurs Care Qual. 1996;11(2):34-40.

18. Warner BW, Kulick RM, Stoops MM, Mehta S, Stephan M, Kotagal UR. An evidencedbased clinical pathway for acute appendicitis decreases hospital duration and cost. J

Pediatr Surg. 1998;33(9):1371-5.
587

19. Willis B, Kim LT, Anthony T, Bergen PC, Nwariaku F, Turnage RH. A clinical pathway

for inguinal hernia repair reduces hospital admissions. J Surg Res. 2000;88(1):13-7.

20. Choong PF, Langford AK, Dowsey MM, Santamaria NM. Clinical pathway for fractured

neck of femur: a prospective, controlled study Med J Aust. 2000;172(9):423-6.

21. Dowsey MM, Kilgour ML, Santamaria NM, Choong PF. Clinical pathways in hip and knee

arthroplasty: a prospective randomised controlled study. Med J Aust. 1999;170(2):59-62.

22. Johnson KB, Blaisdell CJ, Walker A, Eggleston P. Effectiveness of a clinical pathway for

inpatient asthma management. Pediatrics. 2000;106(5):1006-12.

23. Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, Feagan BG. A controlled

trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL

Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing

Levofloxacin. JAMA. 2000;283(6):749-55.

24. Bailey R, Weingarten S, Lewis M, Mohsenifar Z. Impact of clinical pathways and practice

guidelines on the management of acute exacerbations of bronchial asthma. Chest.

1998;113(1):28-33.

25. Chen AY, Callender D, Mansyur C, Reyna KM, Limitone E, Goepfert H. The impact of

clinical pathways on the practice of head and neck oncologic surgery: the University of

Texas M. D. Anderson Cancer Center Experience. Arch Otolaryngol Head Neck Surg.

2000;126(3):322-6.

26. Wong C, Visram F, Cook D, Griffith L, Randall J, O'Brien B, et al. Development,

dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.

CMAJ. 2000;162(1):29-33.

27. Pearson SD, Kleefield SF, Soukop JR, Cook EF, Lee TH. Critical pathways intervention to

reduce length of hospital stay. Am J Med. 2001;110:175-80.
588
589

Chapter 53. Clinical Decision Support Systems

Robert Trowbridge, MD

University of California, San Francisco School of Medicine

Scott Weingarten, MD, MPH

University of California, Los Angeles School of Medicine

Background

Integrating medical knowledge and advances into the clinical setting is often difficult due

to the complexity of the involved algorithms and protocols. Clinical decision support systems

(CDSS) assist the clinician in applying new information to patient care through the analysis of

patient-specific clinical variables.1

 Many of these systems are used to enhance diagnostic efforts

and include computer-based programs such as DxplainTM that provide extensive differential

diagnoses based on clinical information entered by the clinician.2

 Other forms of clinical

decision support systems, including antibiotic management programs and anticoagulation dosing

calculators, seek to prevent medical errors and improve patient safety.3-5

Practice Description

Clinical decision support systems vary greatly in their complexity, function and

application.1

 These clinical tools differ from practice guidelines (Chapter 51) and critical

pathways (Chapter 52) in that they require the input of patient-specific clinical variables and as a

result provide patient-specific recommendations. Guidelines and pathways, in contrast, may not

require the input of such information and provide more general suggestions for care and

treatment. Although many clinical decision support systems are now computer-based, some are

relatively simple, with no inherently complex internal logic systems. Among the most common

forms of support systems are drug-dosing calculators, computer-based programs that calculate

appropriate doses of medications after clinicians input key data (eg, patient weight, indication for

drug, serum creatinine). These calculators are especially useful in managing the administration

of medications with a narrow therapeutic index (see Chapter 9). More complex systems include

computerized diagnostic tools that, although labor intensive and requiring extensive patientspecific data entry, may be useful as an adjunctive measure when a patient presents with a

confusing constellation of symptoms and an unclear diagnosis. Other systems, both simple and

complex, may be integrated into the point-of-care and provide accessible reminders to clinicians

regarding appropriate management based on previously entered data. These systems may be

most practical when coupled with computerized physician order entry and electronic medical

records (see Chapter 6). Finally, through their integration with practice guidelines and critical

pathways, decision support systems may provide clinicians with suggestions for appropriate

care, thus decreasing the likelihood of medical errors. For example, a guideline for the

management of community-acquired pneumonia may include a clinical tool that, after the input

of patient-specific data, would provide a recommendation regarding the appropriateness of

inpatient or outpatient therapy.6
590

Prevalence and Severity of the Target Safety Problem/Opportunities for Impact

A great variety of patient safety issues may be affected by clinical decision support

systems. Since the systems are typically intercalated at the point-of-care, they are likely to have

their greatest effect on problems related to the individual patient. Some of the best studied

applications of decision support systems are those that seek to prevent adverse drug reactions

and inappropriate drug dosing as well as those that facilitate the appropriate use of effective

prophylactic measures, such as those for venous thromboembolic disease (see Chapter 31).4,5

Decision support systems may also help ensure a minimum standard for quality of care as part of

the implementation of practice guidelines by providing patient-specific recommendations after

the input of certain clinical variables. This combination of decision support systems and

guidelines may be especially effective in conjunction with the use of the electronic medical

record.7

 To date no high quality studies have examined the impact of widespread institution of

decision support, but local studies suggest that it may be substantial. An evaluation of an

antibiotic management system in a single 12-bed Intensive Care Unit over a 3 year period

revealed that use of the system resulted in 24 fewer adverse drug reactions and 194 fewer cases

of antibiotic-susceptibility mismatch.4

 These results and others suggest that national

implementation of decision support systems could markedly improve patient safety.

Study Design

The functionality and effectiveness of clinical decision support systems has been

evaluated in a number of systematic reviews. The seminal review, last updated in 1998,

investigated the use of computer-based systems in all clinical settings.3

 The authors completed

an exhaustive search of electronic databases and the bibliographies of pertinent articles and

found 68 prospective trials on the subject. The vast majority of these studies (90%) were

randomized trials. The articles were rated on a 10-point scale for quality. The scale assessed the

design features of the trials, including method of randomization, baseline comparability of the

study groups, allocation unit, outcome measures, and degree of follow-up. The mean score on

this validity scale was 6.4 for studies published prior to 1992 and 7.7 for subsequent studies.

Another systematic review evaluated the use of computer-based decision aids in the

provision of outpatient preventive care.8

 This study, which was based on a search of electronic

databases including MEDLINE, found 16 trials that met the pre-defined inclusion criteria. Only

randomized controlled studies were included. Those that used only historical controls were

excluded. The acceptable studies were then evaluated using weighted mixed effects model

regression analysis.

Yet another systematic review investigated the utility of computer systems in the primary

care setting.9

 A detailed search of several electronic databases and a hand search of

bibliographies and conference proceedings yielded 30 studies that met criteria for inclusion.

These papers were ranked by the same validity score utilized in the systematic review of

computer-based decision supports systems described above. The average validity score of the

included trials was 6.7 on the 1-10 scale.

Most relevant to patient safety per se is a fourth systematic review of the utility of

computers in medication dosing.10 This review, which located studies in the Cochrane

Collaboration on Effective Clinical Practice, was also based on an extensive search of electronic

databases, supplemented by a bibliography search and consultation with experts. Of 16 relevant

studies, all but one were randomized controlled clinical trials. Time series studies were not

included. The included trials were then evaluated using a random effects model.
591

A final systematic review analyzed the utility of computers in the implementation of

practice guidelines which, in such a setting, may be considered clinical decision support

systems.11 A structured search of MEDLINE, CINAHL, bibliographies and books found 25

papers detailing the use of 20 such systems. In this group, there were 10 time series studies (all

without external controls) and 10 controlled trials, 9 of which were randomized.

Two well-designed studies have been published since the above systematic reviews. One

is a cluster randomized trial of the use of a decision support system in the treatment of patients

with hypertension.12 The second is a prospective time series investigation of a decision support

system for the prevention of thromboembolic disease in post-surgical patients.4

Study Outcomes

Most of the reviewed studies reported results in terms of patient outcomes and provider

performance. The most common clinical outcomes (Level 2) included the relative adherence to

specific recommendations and the degree to which prospectively described tenets of “appropriate

practice” were followed. Examples of such principles included whether clinicians followed

medication dosage recommendations and delivered appropriate preventive health care measures.

Several studies reported even more definitive clinical data (Level 1) including the degree of

blood pressure reduction, the incidence of adverse drug reactions, the control of postoperative

pain and percentage of patients with therapeutic drug blood levels.

Evidence for Effectiveness of Practice

The majority of the systematic reviews portray clinical decision support systems in a

positive light. The seminal systematic review of computer-based decision support systems, for

example, found that 43 of the 65 investigated studies showed at least some benefit in either the

process of care or patient outcomes.3

 Most impressively, 74% of the studies of preventive health

care reminder systems and 60% of the evaluations of drug dosing models reported a positive

impact. In addition, 6 of the 14 studies that reported actual patient outcomes reported a beneficial

effect. However only one of the five diagnostic aids, a model used to predict postoperative

pulmonary complications, showed encouraging results. The others, including systems designed

to aid diagnostic efforts in patients with chest and abdominal pain, were ineffective. This review

was rigorously conducted and only those papers with robust study design were included. Overall

it provides compelling evidence for the effectiveness of specific decision support systems.

These results are supported by the review of systems to aid the delivery of preventive

health care.8

 By applying weighted mixed effects model regression analysis to the 16 identified

studies, the authors found decision support systems resulted in significantly improved rates of

delivery of preventive health care (OR 1.77, 95% CI: 1.38-2.27). Computer systems, however,

were not statistically superior to manual reminder systems. Although this study reviewed many

of the same papers that were evaluated in the reviews discussed above, it provides further

evidence of the utility of these systems in improving the process of care.

The review of clinical decision support systems in the outpatient setting provided

similarly encouraging results.9

 All of the 21 studies that examined processes of care found

improvements. Results were somewhat less impressive in the articles reporting more definitive

clinical outcomes including level of blood pressure reduction and patient satisfaction. Only one

of three such studies found significant benefit.

The systematic review of the use of computer models to determine drug doses provides

some of the most compelling evidence for application of decision support systems to patient

safety and error avoidance efforts.10 Seven of the 11 studies showed a beneficial effect on drug
592

dosing, and more significantly, 4 of 6 showed a decrease in adverse drug effects. Five of six also

reported direct positive effects on the patient, including one that reported improved control of

postoperative pain. Since the majority of the analyzed studies were randomized controlled trials,

this review provides powerful evidence that decision support systems may prevent medical

errors and other adverse events. A more recent study of an antibiotic management program also

supports this contention.5

 In this prospective before-after trial, the use of the decision support

system resulted in a substantial and significant decrease in the incidence of adverse drug

reactions (p=0.018) and prescriptions for medications contraindicated by allergy (p<0.01). The

system was also popular among the health care providers, cut costs and saved time (see also

Chapter 6).

Finally, clinical decision aids were useful in implementing practice guidelines. The

systematic review of this subject found favorable effects on guideline adherence in 14 of the 18

papers studied.11

The impact of decision support systems on the outcomes of care for discrete disorders has

also been studied. These results are mixed. For example, the recent randomized controlled trial

of a computer-based system in the treatment of patients with hypertension failed to show any

benefit, and the system was actually out-performed by a paper-based system.12 These findings

corroborated those of a systematic review that questioned the utility of CDSS for treating

hypertension.13

In summary, clinical decision support systems may provide significant benefits in the

process of care, preventing medical errors and prompting physicians to provide appropriate

preventive care measures. Their utility in guiding the treatment of individual clinical disorders

(such as hypertension) remains a matter of study.

Potential for Harm

Most studies show no major adverse effects from the use of CDSSs. Although one study

demonstrated that they may increase a physician’s consultation time (thus decreasing the time

spent on direct patient care),14 others suggest that they may improve efficiency, especially in

terms of data recall.5

 The usefulness and efficiency of such systems is clearly dependent on the

programmed logic. As such they must be with developed with extremely high quality control

standards. A system that provides erroneous information and guidance, for example, has the

potential to cause broad deleterious impact.
593

Costs and Implementation

Very few studies specifically address the cost of developing and implementing decision

support systems. We posit that the costs may be substantial as the majority of systems are now

computer-based and require significant hardware, most commonly placed at the point-of-care. In

addition, many of the successful systems were integrated with computerized medical record

systems and physician order entry (Chapter 6), which are not yet in universal use. The

development and frequent updating of system software is also likely to be very expensive.

Despite these concerns, the widespread implementation of successful systems is feasible and will

likely become even more so as providers and systems increasingly shift to computerized medical

record systems.

Comment

The preponderance of evidence suggests that clinical decision support systems are at least

somewhat effective. Their highest utility has been demonstrated in the prevention of medical

errors, especially when coupled with a computerized medical record and directly intercalated

into the care process. Unlike more passive methods such as education and feedback, decision

support systems are generally able to modify physician behavior and affect the process of care.

Although the results of support systems have been far less positive when used in the ongoing

care of patients with chronic diseases or to help with diagnostic decision making, these

capabilities may improve with further technological advances.

References

1. Payne TH. Computer decision support systems. Chest. 2000;118:47S-52S.

2. Barnett GO, Cimino JJ, Hupp JA, Hoffer EP. DXplain. An evolving diagnostic decisionsupport system. JAMA. 1987; 258: 67-74.

3. Hunt DL, Haynes RB, Hanna SE, Smith K. Effects of computer-based clinical decision

support systems on physician performance and patient outcomes: a systematic review.

JAMA. 1998; 280: 1339-46.

4. Durieux P, Nizard R, Ravaud P, Mounier N, Lepage E. A clinical decision support system

for prevention of venous thromboembolism: effect on physician behavior. JAMA. 2000;

283: 2816-21.

5. Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver LK, Orme JF, et al. A

computer-assisted management program for antibiotics and other antiinfective agents. N

Engl J Med. 1998; 338: 232-8.

6. Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, Feagan BG. A controlled

trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL

Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing

Levofloxacin. JAMA. 2000; 283: 749-55.

7. Shiffman RN, Brandt CA, Liaw Y, Corb GJ. A design model for computer-based guideline

implementation based on information management services. J Am Med Inform Assoc.

1999; 6: 99-103.

8. Shea S, DuMouchel W, Bahamonde L. A meta-analysis of 16 randomized controlled trials

to evaluate computer-based clinical reminder systems for preventive care in the ambulatory

setting. J Am Med Inform Assoc. 1996; 3: 399-409.

9. Sullivan F, Mitchell E. Has general practitioner computing made a difference to patient

care? A systematic review of published reports. BMJ. 1995; 311: 848-52.
594

10. Walton R, Dovey S, Harvey E, Freemantle N. Computer support for determining drug

dose: systematic review and meta-analysis. BMJ. 1999; 318: 984-90.

11. Shiffman RN, Liaw Y, Brandt CA, Corb GJ. Computer-based guideline implementation

systems: a systematic review of functionality and effectiveness. J Am Med Inform Assoc.

1999; 6: 104-14.

12. Montgomery AA, Fahey T, Peters TJ, MacIntosh C, Sharp DJ. Evaluation of computer

based clinical decision support system and risk chart for management of hypertension in

primary care: randomised controlled trial. BMJ. 2000; 320: 686-90.

13. Montgomery AA, Fahey T. A systematic review of the use of computers in the

management of hypertension. J Epidemiol Community Health. 1998; 52: 520-5.

14. Weingarten MA, Bazel D, Shannon HS. Computerized protocol for preventive medicine: a

controlled self-audit in family practice. Fam Pract. 1989; 6: 120-4.
595

Chapter 54. Educational Techniques Used in Changing Provider Behavior

Robert Trowbridge, MD

University of California, San Francisco School of Medicine

Scott Weingarten, MD, MPH

University of California, Los Angeles School of Medicine

Background

A number of techniques have been used to modify the behavior of practicing physicians.1

Continuing medical education, practice guidelines and critical pathways represent a major thrust

of these efforts. The relative effectiveness of each is largely dependent on the particular strategy

employed in their implementation.2

 Traditionally these strategies have focused on lectures and

printed materials but other techniques have also been utilized, including audit and feedback,

academic detailing, local opinion leaders and reminder systems. In addition, some have

championed the use of sentinel event reporting and root cause analysis in graduate medical

education programs.3

 Only recently have these various techniques been critically evaluated for

their effectiveness at changing physician behavior.

This chapter reviews the evidence regarding the utility of educational-oriented techniques

to improve provider behavior, particularly as they do or might pertain to patient safety practices.

Incident reporting (Chapter 4), root cause analysis (Chapter 5), guidelines (Chapter 51),

pathways (Chapter 52), and decision support systems (Chapter 53) are reviewed elsewhere in the

Report.

Practice Description

The passive dissemination of information through the use of lectures, conferences,

mailings and printed materials remains the primary method to alter physician behavior. This

primacy has not been substantially challenged in practice, although more interactive techniques

have increasingly been utilized. Academic detailing, for example, involves the process of having

invested and well-informed agents for change interacting with individual physicians to promote

certain tenets of practice. Alternatively, audit and feedback entails the review and return to the

clinician of their own process of care and patient outcomes (often compared with local or

national benchmarks or evidence-based standards) in the hopes it will result in more appropriate

medical care.3 Reminder systems, which may be computerized and embedded in the electronic

medical record, prompt physicians to provide certain health care measures. They differ from

clinical decision support systems (Chapter 53) in that they may not provide information tailored

to the specific patient. Finally, opinion leaders, usually respected local physicians, may improve

health care by championing “best practices” on a regional basis.4, 5

Prevalence and Severity of Target Safety Problem/Opportunities for Impact

It is well established that physicians are unable to keep abreast of the staggering volume

of published medical literature. This is reflected by the many studies that demonstrate the glacial

pace at which many beneficial advances are incorporated into medical practice. Practice

guidelines, clinical decision support systems and programs for physician education are potential

solutions to this problem, but their effectiveness is greatly dependent on the methods used in

their implementation.2

 Despite the presence of comprehensive guidelines on the treatment of

reactive airways disease, for example, a substantial percentage of asthmatic patients do not
596

receive appropriate care.6, 7 Physician education techniques that reliably impact practice patterns

may yield substantial improvements in patient care and safety.

Study Designs

The Cochrane Group completed a series of systematic reviews of physician education

based on the Research and Development Base in Continuing Medical Education, a central

database compiled from an extensive search of electronic databases and bibliographies and

supplemented by contact with experts in the field. Although the initial review was completed in

1997, reviews are regularly updated as more pertinent data are published. One such study

evaluated the role of audit and feedback and found 37 randomized controlled studies comparing

this technique to non-interventional control groups.3

 An ancillary study by the Cochrane Group

compared audit and feedback with other educational strategies and located 12 randomized

controlled studies for analysis.10 A second study of the effectiveness of audit and feedback was

completed by a separate group that searched MEDLINE and selected bibliographies for trials

investigating the strategy’s utility in improving immunization rates. Fifteen studies were

identified for inclusion, 5 of which were randomized controlled studies with 6 interrupted time

series evaluations and 4 before-after trials.11 A third meta-analysis of peer-comparison feedback

systems used an extensive electronic database and bibliography search to locate 12 randomized

controlled studies.12

The Cochrane Group also investigated the utility of academic detailing and found 18

randomized controlled studies.13 A similar evaluation of local opinion leaders yielded 8

randomized controlled trials.5

A separate Cochrane review was completed on the utility of printed educational materials

using the Cochrane Effective Practice and Organization of Care Group database. The search of

this database, which was compiled in the same manner as the Research and Development Base in

Continuing Medical Education, found 10 randomized controlled trials and one interrupted time

series study fulfilling criteria for analysis.14

Study Outcomes

Few of the studies report outcomes specific to the field of patient safety. The vast

majority are concerned with process of care rather than the outcomes of care. Although clinical

outcomes are reported in at least one of the studies evaluated in each of the systematic reviews

(with one exception), the majority relate outcomes pertaining to physician performance. Some of

the more commonly described variables include the rates of appropriate provision of preventive

care measures and of adherence to appropriate treatment or diagnostic protocols.

Evidence for Effectiveness of Practice

Much of the evidence for the effectiveness of educational and implementation techniques

is of fair quality and the results are generally consistent across the various systematic reviews.

However, methodologic concerns prevented the completion of quantitative data synthesis in the

majority of the reviews. The studies are summarized in Table 54.1.

The initial comprehensive review found overall beneficial effect for 62% of

interventions. In investigations of effect on patient outcomes, 48% had favorable results.

Academic detailing and the use of local opinion leaders were the most effective techniques

evaluated. Physician reminder systems were also effective, as 22 of the 26 evaluated studies

revealed some benefit. The technique of audit and feedback was of marginal effectiveness and

conferences and printed materials were found to be relatively ineffective. Of note, multifaceted
597

interventions with at least 3 components were associated with a 71% success rate.8

 The second

comprehensive review of 102 randomized controlled studies supported these conclusions. Yet it

emphasized that the degree of effect with even the most consistently effective techniques was

moderate at best, and that the process of care rather than the outcome of care was the most

readily influenced variable.9

The Cochrane reviews reported similar results. Audit and feedback was found to be

effective in 62% of the studies in which it was compared with non-interventional controls, but

the effect was typically small. The results were not substantially different when audit and

feedback was augmented by conferences or educational materials or was part of a multifaceted

intervention.3

 In the review of comparative trials, however, this technique was found to be

inferior to reminder systems in 2 of the 3 trials where a direct comparison was made.10 The

second review of audit and feedback, which focused on improving immunization rates, found

beneficial results in 4 of 5 randomized controlled trials evaluated. Statistically significant

changes were present in at least 2 of these evaluations. However, the marginal effect was small

and likely was overwhelmed by the relatively high cost of the intervention.11 Finally the metaanalysis of the 12 randomized controlled trials investigating peer-comparison feedback systems

did establish a modest benefit for the use of audit and feedback (p<0.05), but the magnitude of

benefit was again noted to be small.12

The Cochrane review of academic detailing was somewhat more optimistic. All of the

evaluated studies showed some degree of a beneficial effect on physician performance although

only one of these studies reported patient outcomes. Most combined detailing with other

techniques and there was insufficient evidence to make direct comparisons between detailing and

the other techniques.13

The use of local opinion leaders was also found to be effective by the Cochrane group,

although to a much less convincing degree than academic detailing. Two of 7 trials showed a

statistically significant beneficial effect with a trend toward effectiveness in all 7 studies. One of

3 trials investigating patient outcomes demonstrated a significant benefit.5

Finally, the Cochrane review of the use of printed educational materials supported the

findings of the previous overviews. None of the 9 studies showed a statistically significant effect

when compared with controls and only one of 6 trials that included printed materials in a

multifaceted approach demonstrated benefit. Of note, all of the evaluated trials were plagued by

methodologic shortcomings.14

Potential for Harm

These educational techniques are unlikely to cause significant patient harm.
598

Costs and Implementation

Although the cost-effectiveness of the various educational techniques has not been

explicitly studied, it is clear that several may require substantial outlay in terms of financial

resources and personnel. It also appears that the forms of education that are most effective,

including academic detailing and local opinion leaders, are also the most expensive to design and

support. Programs of printed materials and lectures, although dramatically less effective, are

substantially less expensive to implement. It is unclear whether the integration of Internet

technology and computer-based education initiatives will result in substantial changes in efficacy

or cost. Finally, the relative cost-effectiveness of the various techniques remains unclear.

 Comment

From studies of randomized controlled trials, it appears that academic detailing and local

opinion leaders are frequently associated with at least some benefit. Reminder systems are also

effective in specific situations and the utility of audit and feedback has been established,

although unimpressively. Traditional programs of conferences, lectures and printed materials are

ineffective at inducing changes in physician behavior. None of the current techniques, however,

have demonstrated a consistent ability to induce substantial and durable changes in physician

behavior. The relative cost-effectiveness of the various techniques is uncertain; it remains

unclear if the added cost of the more effective strategies (ie, academic detailing and local opinion

leaders) is justified given their relatively small marginal increase in effectiveness. Finally there

are few data regarding the specific utility of these techniques in increasing patient safety and/or

the prevention of medical errors. However, techniques effective in other areas of medicine are

likely to be equally effective in inducing practices changes to improve patient safety.
599

Table 54.1. Studies of techniques for changing physician behavior*

Study Setting Study

Design

Results

Review of 99 trials assessing the

effect of educational techniques on

physician performance in all clinical

settings8

Level 1A 62% of the interventions were associated with

beneficial results; academic detailing, local opinion

leaders and reminder systems were the most

effective while audit and feedback was less so;

traditional CME programs were ineffective

Review of 102 trials assessing the

effect of educational techniques on

physician performance in all clinical

settings9

Level 1A Academic detailing and local opinion leaders were

the most effective techniques; audit and feedback

and reminder systems were less effective;

multifaceted approaches were effective, especially

at influencing the process of care

Review of 37 randomized controlled

trials of the utility of audit and

feedback in all clinical settings in the

US, Europe and Australia3

Level 1A Eight of 13 studies showed a moderate beneficial

effect with audit and feedback with little change

noted when other interventions were added or a

multifaceted approach was used

Review of 12 trials comparing the

effect of audit and feedback with

other educational techniques on 2194

physicians in all clinical settings10

Level 1A Two of 3 trials showed reminder systems

outperformed audit and feedback; 4 studies

demonstrated little benefit to adding other

modalities to audit and feedback

Review of fifteen studies, of which

five were randomized controlled

trials, investigating the use of audit

and feedback in improving

immunization rates in adults and

children in the outpatient setting in

the US and the UK11

Level 1A Twelve of the 15 studies showed a benefit with

audit and feedback and of the 5 RCTs, 4 showed a

beneficial trend that was significant in at least 2 of

the trials

Review of 18 trials investigating the

effects of academic detailing on 1896

physicians in the US, Canada,

Europe, Indonesia and Australia13

Level 1A All of the evaluated studies showed some degree of

benefit although only one looked specifically at

patient outcomes

Review of 8 randomized controlled

trials investigating the effect of local

opinion leaders on 296 physicians in

the US, Canada and Hong Kong5

Level 1A Six of the 7 studies evaluating effects on physician

performance showed a beneficial effect with 2 of

these being statistically significant; one of the 3

trials evaluating patient outcomes showed a

significantly positive effect

Review of eleven studies evaluating

the effect of printed education

materials on over 1848 physicians in

a variety of clinical settings14

Level 1A None of the studies reported significantly improved

outcomes with the use of printed educational

materials

* CME indicates continuing medical education; RCT, randomized controlled trial.
600

References

1. Smith WR. Evidence for the effectiveness of techniques To change physician behavior.

Chest. 2000; 118: 8S-17S.

2. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic

review of rigorous evaluations. Lancet. 1993; 342: 1317-22.

3. Thomson O'Brien MA, Oxman AD, Davis DA, Haynes RB, Freemantle N, Harvey EL.

Audit and feedback: effects on professional practice and health care outcomes. In: The

Cochrane Library, Issue 2, 2000:Oxford: Update Software.

4. Szilagyi PG, Bordley C, Vann JC, Chelminski A, Kraus RM, Margolis PA, et al. Effect of

patient reminder/recall interventions on immunization rates: A review. JAMA. 2000; 284:

1820-7.

5. Thomson O'Brien MA, Oxman AD, Haynes RB, Davis DA, Freemantle N, Harvey EL.

Local opinion leaders: effects on professional practice and health care outcomes. In: The

Cochrane Library, Issue 2, 2000. Oxford: Update Software..

6. Apter AJ, Van Hoof TJ, Sherwin TE, Casey BA, Petrillo MK, Meehan TP. Assessing the

quality of asthma care provided to Medicaid patients enrolled in managed care

organizations in Connecticut. Ann Allergy Asthma Immunol. 2001; 86: 211-8.

7. Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999:

the Asthma Insights and Reality in Europe (AIRE) study. Eur Respir J. 2000; 16: 802-7.

8. Davis DA, Thomson MA, Oxman AD, Haynes RB. Changing physician performance. A

systematic review of the effect of continuing medical education strategies. JAMA. 1995;

274: 700-5.

9. Oxman AD, Thomson MA, Davis DA, Haynes RB. No magic bullets: a systematic review

of 102 trials of interventions to improve professional practice. CMAJ. 1995; 153: 1423-31.

10. Thomson O'Brien MA, Oxman AD, Davis DA, Haynes RB, Freemantle N, Harvey EL.

Audit and feedback versus alternative strategies: effects on professional practice and health

care outcomes. In: The Cochrane Library, Issue 2, 2000. Oxford: Update Software.

11. Bordley WC, Chelminski A, Margolis PA, Kraus R, Szilagyi PG, Vann JJ. The effect of

audit and feedback on immunization delivery: a systematic review. Am J Prev Med. 2000;

18: 343-50.

12. Balas EA, Boren SA, Brown GD, Ewigman BG, Mitchell JA, Perkoff GT. Effect of

physician profiling on utilization. Meta-analysis of randomized clinical trials. J Gen Intern

Med. 1996; 11: 584-90.

13. Thomson O'Brien MA, Oxman AD, Davis DA, Haynes RB, Freemantle N, Harvey EL.

Educational outreach visits: effects on professional practice and health care outcomes. In:

The Cochrane Library, Issue 2, 2000. Oxford: Update Software.

14. Freemantle N, Harvey EL, Wolf F, Grimshaw JM, Grilli R, Bero LA. Printed educational

materials: effects on professional practice and health care outcomes. In: The Cochrane

Library, Issue 2, 2000. Oxford: Update Software.
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Chapter 55. Legislation, Accreditation, and Market-Driven and Other

Approaches to Improving Patient Safety

Robert Trowbridge, MD

Robert M.Wachter, MD

University of California, San Francisco School of Medicine

Background

Although conventional approaches to health care quality improvement based on

educating providers and offering feedback have been proposed, the tremendous public and

professional concerns raised by the Institute of Medicine’s report on medical errors1

 have led to

an unusual amount of interest in regulatory and legislative efforts to improve safety. Given the

traditional American dependence on education, competition, and other non-coercive mechanisms

of change, the shift toward a regulatory approach is evidence of the depth of concern this issue

has engendered. As these regulatory and legislative approaches are considered, it is also

worthwhile to consider the role of health care payers, hospital accreditation organizations, and

professional societies, all of whom have also led safety initiatives.2-4 This chapter considers the

potential advantages and disadvantages of legislative, regulatory, professional society, and

market-oriented approaches to implementing patient safety efforts, and reviews the evidence

regarding their effectiveness.

Government Legislation and Regulation

The concept of patient safety has been championed by several prominent legislators in

both major political parties and has become the topic of a great deal of national debate. Proposals

to date include the establishment of voluntary and mandatory error reporting systems, the

publication of outcomes data, and the development of several Health Care Financing

Administration (HCFA) programs to prevent medical errors.5

 In addition, in 2000 the Agency for

Healthcare Research and Quality (AHRQ) established a Center for Quality Improvement and

Patient Safety, whose mandate in part is to fund research and demonstration projects in patient

safety. Though most of these Federal efforts are in the formative stages,6

 successful Federal

agency and regulatory efforts outside of medicine, most notably in workplace safety and

commercial airline travel, may herald medicine’s success. In these fields, the Occupational

Safety and Health Administration (OSHA) and the Federal Aviation Administration (FAA) are

credited with catalyzing significant improvements in safety over the past 30 years.7, 8

Despite a paucity of data regarding the effect of State legislation on medical errors and

patient safety, there is some evidence regarding the effectiveness of State regulatory efforts to

improve health care quality.9-11 Among the most prominent set of regulations are the New York

State enactments as a result of the death of Libby Zion.

The daughter of a prominent reporter, Ms. Zion died soon after being admitted to the

medical service of a New York City hospital. A detailed investigation of the circumstances of

her death subsequently raised concerns regarding working conditions and the supervision of

resident physicians. The Bell Commission, formed at the behest of the New York State Health

Commissioner, later recommended major reform in these areas and several regulations were

enacted mandating dramatic changes in working conditions and supervisory oversight.12

These regulations markedly altered resident physician education in New York State.

Although they anecdotally resulted in an improvement in resident morale and quality of life,13
602

their effect on patient safety is less certain. One retrospective cohort study demonstrated that

patients treated after the work-hour limitations were instituted were more likely to suffer from

complications and delays in the performance of diagnostic tests.11 A second retrospective

analysis of patient transfer-of-care, a bi-product of restricting resident work-hours, showed

increased lengths of stay and utilization of laboratory testing for patients that were “handed

off.”

10 A third study, however, revealed exactly contradictory results. It found the work-hours

limitations led to shorter lengths of stay and fewer medication errors.9

 These studies have been

criticized for concentrating on the work-hour regulations when the main finding of the Bell

Commission was that increased supervision of resident physicians was a more important

initiative.14 (See Chapter 46 for a more complete discussion of fatigue and work hours).

Although regulations to improve patient safety might be a more efficient way of

changing practice than less coercive methods such as education or feedback, the use of

government regulation in the assurance of patient safety has limitations. A primary concern is

that regulations may be crafted by legislators who lack intimate knowledge of the health care

system. In addition, health care in the United States is extremely heterogeneous - what may be

feasible and appropriate in one setting may be inapplicable in another. The differences between

the delivery of care in urban and rural settings may be particularly troublesome in this regard.

Finally, it is unclear whether government agencies would provide adequate funding to assist

health care organizations to comply with new regulations. For example, a cash-starved institution

faced with a resident work-hours mandate might need to decrease nurse staffing or defer

purchase of a computerized order entry system to meet the mandate.

Government agencies may also influence patient safety practices through means other

than direct legislation. For example, the National Nosocomial Infections Surveillance (NNIS)

system may serve as a template for the development of a government-sponsored safety program.

Established and administered by the Centers for Disease Control and Prevention (CDC), the

NNIS is a voluntary nationwide consortium of 300 hospitals that regularly report the incidence

of specified nosocomial infections.15 Through analysis of the aggregate data, benchmarks are set

for the expected rates of nosocomial infection that hospitals may then strive to meet or better.

There is some evidence that the NNIS has contributed to a substantial decline in the rate of

nosocomial infections over the past several decades.16 It is conceivable that a similar program

could be established for broader patient safety issues. Although voluntary and lacking

enforcement power, NNIS-like patient safety benchmarking could significantly improve safety,

especially if the data were made available to the public or accreditation agencies.

Infection control officers, another aspect of the CDC-championed infection control

movement, may also be applicable to the patient safety movement. Presently, infection control

officers employed by medical centers focus on improving the system and changing practices to

decrease the institutional rates of serious infections. An institutional “patient safety officer”

might assume an analogous function with regard to decreasing adverse events and errors. The

establishment of a patient safety officer or committee is one of the new Joint Commission on

Accreditation of Healthcare Organization’s (JCAHO) safety standards (discussed below). To

date, there are no data regarding the effectiveness of these practices in patient safety.

Accreditation Organizations

Accreditation organizations represent another sector of the health care industry that is

assuming new responsibilities in the field of patient safety. JCAHO, an outgrowth of

accreditation programs initiated by the American College of Surgeons several decades ago, is the

best known of these organizations. JCAHO conducts meticulous inspections of medical centers,
603

hospitals and other health care institutions on a triennial basis. Survey results are subsequently

used in the process of obtaining Medicare certification and State licensure and to obtain bond

ratings and managed care contracts. Although such inspections had previously included some

elements relating to the field of patient safety (including infection control and the prevention of

medication errors), they tended to focus on organizational topics including information

management, institutional leadership and strategic planning.17 In response to concerns regarding

patient safety, however, JCAHO has recently launched a major patient safety initiative and

implemented an entirely new set of standards in July 2001.18

The new JCAHO standards place a much greater emphasis on the prevention of medical

errors and the process of responding to medical errors once they occur. A particular focus of the

new initiative is the development of organization-specific patient safety programs. Such

programs, which will undoubtedly require substantial resources to implement, are expected to

have well-defined leadership, to proactively determine areas where errors are likely to occur, and

to be capable of effecting significant organizational change when necessary. The key elements of

these standards are listed in Table 55.1.

Although there is no published evidence that the patient safety standards previously

required by JCAHO have reduced medical errors, it seems reasonable to assume they have had

some salutary effect.6

 Because JCAHO reports are now publicly available and are used by a wide

variety of credentialing agencies and health care purchaser organizations, many hospitals and

other medical institutions will make serious and concerted efforts to meet the new standards.

Although lacking the enforcement power of Federal regulations, the agencies’ knowledge of, and

contacts within the medical community may produce change more efficiently. Moreover, the

process of accreditation involves frequent site visits between the agencies and health care

organizations. These visits, in turn, may allow for interactions between institutions and

accreditors which, under ideal circumstances, could allow for user input in to modifications of

regulations. How often this ideal is realized is not known, and some observers have questioned

JCAHO’s overall effectiveness.19-21

Health Care Purchaser Initiatives

The business community has also reacted to the perceived crisis of safety in health care.

The most prominent example is the Leapfrog Group.3

 Sponsored by a consortium of major

corporate chief executive officers known as the Business Roundtable, the Leapfrog Group’s

stated commitment is “to mobilize employer purchasing power to initiate breakthrough

improvements in the safety of health care for Americans.”

22 Large volume purchasers of health

care, including Aetna, ATT, IBM and many other Fortune 500 companies, have joined the group.

Combined, their annual health care outlay is over $45 billion. Using their considerable financial

influence, the group hopes to impact medical care by requiring or incentivizing health care

providers to adhere to certain standards for the process and delivery of care.22

Thus far the Leapfrog consortium has chosen to promote 3 patient safety practices: the

use of computerized physician order entry (Chapter 6), the involvement of critical care

physicians in the care of intensive care unit patients (Chapter 38), and the use of evidence-based

hospital referral systems (Chapter 18).23 The latter practice refers to the referral of patients to

hospitals with the highest volume and best outcome figures for certain elective medical

procedures and treatments. These initiatives were selected because there is substantial evidence

that they enhance quality of care and their implementation is both feasible and easily assessed.

Initial research sponsored by the group suggests that implementing just these 3 strategies could

prevent almost 60,000 deaths per year and avoid over 500,000 errors in medication
604

administration.24, 25 It is anticipated that other quality-related practices (some directed at patient

safety targets) will be added to the list as evidence for their effectiveness is accumulated.

The Leapfrog Group has also begun to outline a program to improve compliance with the

target practices. Plans include rewarding complying providers with an increased number of

patients, increasing remuneration for specific services, and providing public recognition. General

quality will be assessed and publicized through the use of rankings, including those assigned by

JCAHO and other accreditation organizations.23 In addition, the employees of participating

companies will be encouraged to become more active in choosing providers that meet the

Leapfrog standards.

Although the Leapfrog initiative is in its nascent stages and there is presently no

objective evidence that it will favorably impact patient safety, the sheer financial clout of the

involved corporations may catalyze rapid and meaningful change. As with government

regulation, it is unclear which sector of the health care industry will bear the brunt of the

implementation costs. The institution of computerized order entry systems, for example, will

require substantial financial outlays (several million dollars in hardware, software and training

for the average hospital; see Chapter 6) that hospitals and medical groups may find extremely

difficult to absorb without assistance. Additionally, physicians and other health care providers

may resist changes forced upon them from outside medicine, or may “game the system” to create

the appearance of change simply to meet the standards.26 Finally, purchaser initiatives may

create disparities in the level of patient safety among socioeconomic groups if the changes they

promote are only required of health care institutions that provide care to insured members of the

group.

Other Approaches

Professional Societies

Some of the earliest efforts to improve patient safety were actually directed by medical

professional societies rather than outside regulators, accreditors, or legislative bodies. The

American Society of Anesthesiologists (ASA), for example, formed the Anesthesia Patient

Safety Foundation in 1984 and has since promulgated a number of reforms that have

substantially changed the routine practice of anesthesia. Safety measures such as continuous

electrocardiographic monitoring, pulse oximetry and preoperative evaluation were strongly

championed by these organizations through the dissemination of quality standards and

newsletters.1

 While no evidence directly links these initiatives to improved patient safety, there

is little doubt that these reforms resulted in substantial advances. In fact, the standards of care

promoted by the ASA have been widely adopted and now represent the recognized minimum

level of appropriate care.4

 It is nonetheless difficult to separate the effects of these standards

from secular trends associated with technological and clinical advances.

Although medical professional societies do not possess the regulatory might of the

Federal government or the financial power of large health care purchasers, their standing in the

medical community and collective clinical experience are great advantages. It is well established

that physicians are more apt to follow practice guidelines sponsored by respected medical

societies than those issued by the government or industry.27 Society-based programs are also

likely to allow for more provider input and may be more amenable to frequent modification.

Unfortunately, because they lack the power to compel, society recommendations cannot be the

sole agent of change, especially when the evidence supporting a practice is extremely strong and

the stakes are high. It is important to recognize that society recommendations carry a potential
605

for bias, particularly when the recommended changes may have an economic impact on society

members.

Publication of Performance Data

Each of the large entities described above (legislatures, accrediting bodies, purchasers,

payers, and professional societies) may choose to disseminate performance data to the public as

part of its quality improvement strategy. To date, most such report cards have focused on

discrete quality outcomes for single diseases or procedures (eg, mortality after coronary

angioplasty) rather than patient safety targets such as error or nosocomial infection rates.

Nonetheless, implicit in the vigorous debate regarding mandatory error reporting systems is the

question of whether public reporting of performance data is effective in either motivating

provider change or facilitating informed choices by patients.

Marshall and colleagues recently reviewed the evidence regarding the impact of public

reporting systems.28 They found that such systems had a relatively small impact on patients (the

potential users of the data), but a greater impact on the hospitals (the sources of the data). They

posit that the impact is growing as the public becomes increasingly comfortable with both the

concept and interpretation of quality reports. Although some have claimed that public reporting

systems, such as New York State’s Cardiac Surgery Data System (which has reported riskadjusted coronary bypass outcomes since 1990), have led to major improvements in quality,29

this remains controversial.30 Proponents point to New York’s falling bypass mortality rate as

evidence of the value of public reporting, but there is some evidence that the fall in the rate was

due to outmigration of high-risk patients to other states rather than true quality improvement.31

Comment

Concerns about medical errors have spurred many organizations and institutions to

launch major patient safety initiatives. Perhaps because they represent a relatively recent

development or because empirical measurement of such macro-changes is difficult (isolating the

effects of individual interventions vs. other confounding influences), there is little objective

evidence either to determine if they will result in meaningful change or to consider their relative

advantages and disadvantages (Table 55.2). Yet Federal and State governments, accreditation

agencies such as JCAHO, and health care purchasers such as the Leapfrog Coalition, in

combination and independently, may eventually be highly effective champions of patient safety

initiatives. In addition, professional medical societies, given their influential role in the medical

community, are effective agents of change in certain circumstances. The work and involvement

of these diverse, powerful organizations and institutions may prove to be valuable adjuncts to the

more traditional mechanisms of change represented by practice guidelines, continuing medical

education programs, and decision support systems.
606

Table 55.1. New JCAHO safety standards

-Development of a leadership individual or group to devise and implement a

comprehensive patient safety program

-Development of a proactive error prevention program that includes means of identifying

potentially high risk areas

-Development of systems for the reporting of errors

-Development of an error-response system including protocols for root cause analysis

-Requirement for an annual report discussing errors, the response to errors and the

programs initiated to prevent future errors

-Requirement for hospital leaders to set “measurable objectives” for patient safety

programs

-Requirement for educational initiatives for employees, stressing the concept of patient

safety
607

Table 55.2. A comparison of non-local methods to promote patient safety practices

Approach Example Advantages Disadvantages

Legislation “Libby Zion”

laws limiting

resident work

hours

-potential for widespread

implementation

-supported by government

enforcement ability

-inflexible

-limited acceptance by health

care providers

-potential to be developed with

inadequate input from providers

and experts

-may be politically driven with

limited applicability

-may not provide for costs of

implementation, leading to costshifting away from other

beneficial patient safety

practices

Accreditation JCAHO patient

safety standards

-may be more flexible and

more easily modified than

legislation

-implemented at the level of

the health care organization

-health care providers may

have the opportunity for input

-dependent on voluntary

participation in the accreditation

process

-limited enforcement ability

-generally assessed only every

few years

Market-based The Leapfrog

Group

-uses the power of the market

to induce change (may be

more acceptable for many

providers than regulatory

solutions)

-may involve carrot (eg, higher

payments for better practices

or outcomes) rather than stick

alone to achieve impact

-potential to cause disparity in

care among groups not covered

by initiatives

-limited acceptance by health

care providers

-potential for standards to

develop with inadequate input

from health care providers

-change is not required, and

therefore implementation may

be limited

Professional

Societies

Anesthesia

Patient Safety

Foundation

-readily accepted by health

care providers

-developed by providers

themselves, leading to better

“buy in”

-more easily modified when

new evidence or changes in

practice emerge

-minimal enforcement potential;

depends largely on voluntary

participation by practitioners

-potential for bias by

professional societies
608

References

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2. Jencks SF. The government's role in hospital accountability for quality of care. Jt Comm J

Qual Improv. 1994; 20: 364-9.

3. Milstein A, Galvin RS, Delbanco SF, Salber P, Buck CR. Improving the safety of health

care: the leapfrog initiative. Eff Clin Pract. 2000; 3: 313-6.

4. Gaba DM. Anaesthesiology as a model for patient safety in health care. BMJ. 2000; 320:

785-8.

5. Parsons DW. Federal legislation efforts to improve patient safety. Eff Clin Pract. 2000; 3:

309-12.

6. Brennan TA. The role of regulation in quality improvement. Milbank Q. 1998; 76: 709-31,

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7. Occupational Safety and Health Administration; About OSHA. Available at:

http://www.osha.gov/as/opa/osha30yearmilestones.html. Accessed May 8, 2001.

8. NTSB Aviation Accident/Incident Database: Accidents and Accident Rates by NTSB

Classification Federal Aviation Administration. Available at:

http://nasdac.faa.gov/asp/fw_ntsb.asp. Accessed May 8, 2001.

9. Gottlieb DJ, Parenti CM, Peterson CA, Lofgren RP. Effect of a change in house staff work

schedule on resource utilization and patient care. Arch Intern Med. 1991; 151: 2065-70.

10. Lofgren RP, Gottlieb D, Williams RA, Rich EC. Post-call transfer of resident

responsibility: its effect on patient care. J Gen Intern Med. 1990; 5: 501-5.

11. Laine C, Goldman L, Soukup JR, Hayes JG. The impact of a regulation restricting medical

house staff working hours on the quality of patient care. JAMA. 1993; 269: 374-8.

12. DeBuono BA, Osten WM. The medical resident workload: the case of New York State.

JAMA. 1998; 280: 1882-3.

13. Piver CJ. Residency training under New York's new regulations. N Engl J Med. 1991; 324:

273-4.

14. Bell BM. Supervision, not regulation of hours, is the key to improving the quality of

patient care. JAMA. 1993; 269: 403-4.

15. National Nosocomial Infections Surveillance (NNIS) System report, data summary from

January 1990-May 1999, issued June 1999. Am J Infect Control. 1999; 27: 520-32.

16. Monitoring hospital-acquired infections to promote patient safety–United States, 1990-

1999. MMWR Morb Mortal Wkly Rep. 2000; 49: 149-53.

17. Braun BI, Koss RG, Loeb JM. Integrating performance measure data into the Joint

Commission accreditation process. Eval Health Prof. 1999; 22: 283-97.

18. Joint Commission on Accreditation of Healthcare Organizations, Standards, Standards

Revisions for 2001, Leadership Chapter. Available at:

http://www.jcaho.org/standards_frm.html. Accessed May 3, 2001.

19. Weiner CL. The Elusive Quest: Accountability in Hospitals. New York: Aldine De

Gruyter; 2000.

20. Dame L, Wolfe SM. The failure of "private" hospital regulation: An analysis of the Joint

Commission on Accreditation of Healthcare Organizations' inadequate oversight of

hospitals. Washington DC: Public Citizen Health Research Group; 1996.
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21. Yessian M. The external review of hospital quality: the role of accreditation (OEI-01-97-

00051). Boston: Office of Evaluations and Inspections, Office of Inspector General,

Department of Health and Human Services; 1999.

22. The Leapfrog Group for Patient Safety: About Us. Available at:

http://www.leapfroggroup.org/about.htm. Accessed May 3, 2001.

23. The Leapfrog Group. The Leapfrog Group for Patient Safety: Patient Safety. Available at:

http://www.leapfroggroup.org/safety1.htm. Accessed May 3, 2001.

24. Young MP, Birkmeyer JD. Potential reduction in mortality rates using an intensivist model

to manage intensive care units. Eff Clin Pract. 2000; 3: 284-9.

25. Birkmeyer JD B, CM, Wennberg DE, Young M. The Leapfrog Group. Leapfrog Patient

Safety Standards: The Potential Benefit of Univeral Adoption. Available at:

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26. Simborg DW. DRG creep: a new hospital-acquired disease. N Engl J Med. 1981; 304:

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27. Hayward RS, Guyatt GH, Moore KA, McKibbon KA, Carter AO. Canadian physicians'

attitudes about and preferences regarding clinical practice guidelines. CMAJ. 1997; 156:

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data: what do we expect to gain? A review of the evidence. JAMA. 2000; 283: 1866-74.

29. Mukamel DB, Mushlin AI. Quality of care information makes a difference: an analysis of

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Mortality Reports. Med Care. 1998; 36: 945-54.

30. Hannan TJ. Detecting adverse drug reactions to improve patient outcomes. Int J Med Inf.

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31. Omoigui NA, Miller DP, Brown KJ, Annan K, Cosgrove D, 3rd, Lytle B, et al.

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610
611

PART V. ANALYZING THE PRACTICES

Chapter 56. Methodology for Summarizing the Evidence for the Practices

Chapter 57. Practices Rated by Strength of Evidence

Chapter 58. Practices Rated by Research Priority

Chapter 59. Listing of All Practices, Categorical Ratings, and Comments
612
613

Chapter 56. Methodology for Summarizing the Evidence for the Practices

Background

The Agency for Healthcare Research and Quality (AHRQ) charged the UCSF-Stanford

Evidence-based Practice Center with the task of rating or grading the patient safety practices

identified and evaluated in this Report. The Report is an anthology of diverse and extensive

patient safety practices, grouped by general topic (Part III, Sections A-H), and then further sorted

within chapters by individual practices. Synthesis was challenging, but critical in order that

readers and health care decision-makers could make judgments about practices to implement

and/or research further. Keeping these two audiences in mind, we set 3 goals for “rating” the

practices, as follows:

• Develop a framework for rating the main elements of practices within the

constraints of the available literature, providing as much pragmatic

information as possible to decision-makers who might endorse practices or

fund further research in the area of patient safety interventions;

• Document the limitations of the rating method so that those “taking home”

messages from the report understand the inherent limitations of making

comparisons of a highly heterogeneous field of possible practices; and

• Convey the results of the ratings in an organized, visually appealing,

accessible way that ensures that our cautionary notes regarding

oversimplifying the ratings are clear.

Ultimately, we aimed to weight the practices, based on the evidence, on a range of

dimensions, without implying any ability to calibrate a finely gradated scale for those practices

in between. Proper metrics for these comparisons (eg, cost-effectiveness analysis) require more

data than are currently available in the literature.

Data Inputs into the Practice Ratings

For each practice, information about various inputs into the final “roll-up”, as we referred

to our scoring of the practices, were prospectively determined. The decision about what

information to attempt to gather was based on the potential expected uses of summary tables of

practices. Three major categories of information were gathered to inform the rating exercise:

• Potential Impact of the Practice: based on prevalence and severity of the

patient safety target, and current utilization of the practice

• Strength of the Evidence Supporting the Practice: including an assessment of

the relative weight of the evidence, effect size, and need for vigilance to

reduce any potential negative collateral effects of practice implementation

• Implementation: considering costs, logistical barriers, and policy issues

Further clarification of the 3 categories is in order. Authors were asked to report on

prevalence and severity of the safety target for a given practice in order to categorize the

potential impact of implementing the practice. We added to this an assessment of the practice’s

potential impact by reviewing evidence of its current utilization. If an intervention is already

widely used, the room for improvement, stated in terms of additional reductions in adverse

events targeted by the practice that could be achieved by wider implementation, is less than if

few are currently using the practice. Thus, potential impact of implementing the practice is a
614

function of the prevalence and severity of the patient safety target (eg, medical error) and the

current utilization of the practice.

Of course the actual impact of any practice is assessable only if factors related to

evidence supporting the practice are evaluated. Since the Report represents an assemblage of

the evidence for patient safety practices, the instructions to authors outlined the detailed data

elements related to study design and outcomes we required them to abstract from the relevant

studies (see Chapter 3). This information was used to assess, in general terms, the overall

strength of the studies for each practice. Effectiveness is commonly defined as the net positive

effect in routine practice. Frequently the data reported in the studies related to efficacy, usually

the net positive effect under controlled, experimental situations. The translation from efficacy to

effectiveness is not straightforward if no direct evidence is available, and is therefore based on

judgments about the generalizibility of the specific research studies conducted. Also of key

importance, and therefore abstracted from studies for use in the ratings, was the effect size of the

intervention.

Finally, evidence-based reviews consider the potential for harm from a medical

intervention, and authors were asked to report on any relevant evidence, as well as reasoned

concerns, gleaned from the literature or from common knowledge about a practice.

To address the real-world environment and the desire by the public for action in the area

of patient safety, practice chapters were designed to include information about cost and other

potential barriers to implementation. While authors sometimes discussed cost savings or

reported cost-effectiveness analyses, the focus was on the start-up costs and annual outlays for

ongoing use of the practice. Although initial and ongoing costs are a function of local

environments (eg, size of the health care network or institution), possible cost savings are likely

to be even more subject to local conditions (eg, prevalence of the patient safety target). For

major investment decisions, an assessment of tradeoffs is more appropriate at the local level. 

Our intention was simply to report “ballpark” estimates of initial and recurring costs. Separate

from economic consequence of a particular practice implementation are the political and

technical considerations.

For all of these data inputs into the practice ratings, the primary goal was to find the best

available evidence from publications and other sources. Because the literature has not been

previously organized with concurrent considerations of each of these areas, most estimates could

be improved with further research and some are informed by only general and somewhat

speculative knowledge. Where possible, in the summaries of these elements, we have attempted

to highlight assessments made on the basis of limited data.

Rating Process

The 4-person Editorial Team developed a rating form that captured the patient safety

target, practice description, and general rating categories (eg, High, Medium, Low) for some of

the elements described in the section above. General heuristics were specified for each category,

although individual judgment for ratings was designed into the process. The form also specified

comment areas to allow raters to document their specific judgments and concerns about ratings. 

Each chapter was independently rated by each Editor as to the practices for which there was

evidence. The Editorial Team convened for 3 days to compare scores, discuss disparities, and

come to consensus about ratings–both by category and summary ratings–or the reviewed

practices.
615

Details about Decision Rules and Judgment Considerations

Potential Impact Factor

As noted above, an assessment of potential impact considered the prevalence and severity

of the patient safety target, and the current utilization of the practice being evaluated. The

Editorial Team used the data from the chapters and clinical knowledge to order the potential

impact as “High,” “Medium,” “Low,” or “Insufficient Information.” To qualify for the “High”

score, a practice had to target a patient population of greater than 1% of hospitalized patients

(about 300,000 patients per year) or target a patient safety problem that can result in death or

disability. The “Low” score was used for target populations of less than 0.01% of hospitalized

patients (about 3000 patient/year) who might experience reversible adverse effects if an effective

practice were not available. Potential impact was deemed a “Medium” if the practice had a

patient safety target that fell between the 2 other categories.

An additional decision rule was applied to the Impact rating after the initial assessment

based on prevalence and severity was made. If a practice was currently widely used (>75% of

hospitals), then the rating was demoted one notch (ie, from High to Medium or Medium to Low).

When this situation occurred, a notation identified that the potential impact level was impacted

by its high current utilization.

We reserved the “Insufficient Information” category for those cases where the prevalence

and severity information was quite limited or where the patient safety target was ill-defined.

Evidence Supporting the Practice

Study strength, effect size on target(s), and need for vigilance due to potential harms

were rated based more on judgment than pre-specified decision rules. In each case, raters

documented their reasons for category choices.

For study strength, the level of study design and outcomes (see Chapter 3 for

hierarchies), number of studies, numbers of patients in studies, generalizability, and other

methodologic issues were specified as factors to consider in weighting the relative study strength

for a particular practice. Study strength could be categorized as “High,” “Medium,” or “Low.”

The actual findings of the studies were not considered when scoring study strength because this

information was captured in the assessment of effect size on target. If there was minimal or no

evidence about a practice, the study strength rating was “Low” and raters did not score the

remaining 2 elements of the evidence supporting the practice since that might give undue

“credit” to the findings.

The assessment of effect size on target(s) was based on the relative risk reductions or

odds ratios reported in the reviewed studies for evidence of effectiveness. The raters only used

the findings reported in the practice chapters, and did not perform additional analyses (eg, metaanalysis). If all studies or, in cases where there were a large number of studies, the vast majority

showed a positive and appreciable effect size (ie, greater than 15% relative risk reduction), then

the positive effect size was categorized as “Robust.” If there was clearly no effect or a very

minimal effect (ie, less than 5% relative risk reduction), then the positive effect size was rated as

“Negligible.” For findings that were considered suggestive of substantive effect, but not clearly

“Robust,” the category used was “Modest.” The final category, “Unclear,” captured those

practices for which the effect size results were inconsistent.

For any given practice that reduces one adverse event, it is conceivable that new

problems might ensue when the practice is implemented. Thus, we subjectively rated the
616

concern for harm based on the level of vigilance necessary to ensure that the practice, if

implemented, would not result in collateral negative effects. The categories available were

“Low,” “Medium,” and “High.” Thus, a practice rated as “Low” would require little to no

attentiveness to potential harms, while one rated as “High” would merit heightened monitoring

for potential negative effects. These ratings were made conservatively, meaning that when in

doubt, a higher vigilance category was selected.

Implementation

Assuming a 3-year lead time for implementation, patient safety practices were rated for

their costs and complexity. Costs were based on initial start-up and annual expenditures for full

implementation at an average size hospital or health care organization. Potential cost savings

were not considered for the rating, but were reported in the practice chapters if they were

documented in the literature. If a practice was expected to require expenditures of greater than

about $1 million, the rating was “High.” Expenditures of approximately $100,000-$1 million

were categorized as “Medium.” Below this level, practices were rated as “Low” in terms of cost.

The feasibility of implementation was rated by considering potential political (eg, major

shifts in who delivers care) and technical (eg, integration of legacy and newer computer systems)

obstacles. Because relatively few data exist for rating implementation complexity, we used only

2 categories, “Low” and “High,” meaning relatively easy and relatively difficult. In cases in

which implementation could be accomplished simply with the expenditure of dollars, we gave

high cost scores but low feasibility scores.

Overall Rating for Impact/Evidence

In addition, each member of the team considered the totality of information on potential

impact and evidence supporting the practice to score each on a 0 to 10 scale (“Strength of the

Evidence”). For these ratings, we took the perspective of a leader of a large health care

enterprise (eg, a hospital or integrated delivery system) and asked the question, “If you wanted to

improve patient safety at your institution over the next 3 years and resources were not a

significant consideration, how would you grade this practice?” For this rating, we explicitly did

not consider difficulty or cost of implementation in the rating. Rather, the rating simply

reflected the strength of the evidence regarding the effectiveness of the practice and the probable

impact of its implementation on reducing adverse events related to health care exposure. If the

patient safety target was rated as “High” impact and there was compelling evidence (ie, “High”

relative study strength) that a particular practice could significantly reduce (eg, “Robust” effect

size) the negative consequences (eg, hospital-acquired infections), raters were likely to score the

practice close to 10. If the studies were less convincing, the effect size was less robust, or there

was a need for a “Medium” or “High” degree of vigilance because of potential harms, then the

rating would be lower.

Overall Rating for Research Priority

Analogously, we also rated the usefulness of conducting more research on each practice,

emphasizing whether there appeared to be questions that a research program might have a

reasonable chance of addressing successfully (“Research Priority”). Here, our “thought

question” was, “If you were the leader of a large agency or foundation committed to improving

patient safety, and were considering allocating funds to promote additional research, how would

you grade this practice?” If there was a simple gap in the evidence that could be addressed by a

research study or if the practice was multifaceted and implementation could be eased by
617

determining the specific elements that were effective, then the research priority was high. If the

area was one of high potential impact (ie, large number of patients at risk for morbid or mortal

adverse events) and a practice had been inadequately researched, then it also would also receive

a relatively high rating for research need. Practices might receive low research scores if they

held little promise (eg, relatively few patients affected by the safety problem addressed by the

practice or a significant body of knowledge already demonstrating the practice’s lack of utility). 

Conversely, a practice that was clearly effective, low cost and easy to implement would not

require further research and would also receive low research scores.

Caveats to Ratings

For all elements assessed, divergent assessments among the 4 Editor-raters were

infrequent and were discussed until consensus was reached. For each final category where

differences in interpretation existed and persisted after discussion, the protocol was to document

a comment about these differences (see Chapter 59). Comments were also noted when specific

additional information could clarify concerns about fidelity of a specific rating. In a few cases,

categories that had not been specified were created for unusual circumstances and again

comments to explain the category were documented.

Rating Tables

Information Captured

Ratings were recorded on a data table, and comments were footnoted. Summarizing from

the previous discussion, the various data tables appearing in Chapters 57-59 captured some or all

of the following 11 elements and rating categories, ordered from strongest to weakest:

1. Chapter number

2. Patient safety target(s)

3. Patient safety practice description

4. Potential Impact: High, Medium, Low, Insufficient Information

5. Study Strength: High, Medium, Low

6. Effect Size: Robust, Modest, Negligible, Unclear

7. Vigilance: Low, Medium, High

8. Implementation cost: Low, Medium, High

9. Implementation complexity (political, technical): Low, High

10. Overall rating for impact/evidence: 0 to 10 (10 is highest), in 0.5 increments

11. Overall rating for research need: 0 to 10 (10 is highest), in 0.5 increments

Information Reported

Chapter 59 presents the detailed data tables with categorization of elements 1-9 above. 

Reporting specific scores for the overall ratings would imply a refinement in scoring that was

neither attempted nor advisable given the nature of the information available. Where applicable,

caveats to the categorizations are appended in a series of endnotes.

In rating both the strength of the evidence and the research priority, our purpose was not

to report precise 1-10 scores, but to develop general “zones” or practice groupings. As noted

earlier, better methods are available for comparative ratings when the data inputs are available. 

The relative paucity of the evidence dissuaded us from using a more precise, sophisticated, but

ultimately unfeasible, approach.
618

Chapter 57 summarizes the overall ratings for the “Strength of the Evidence" regarding

their impact and effectiveness score, and subdivides the practices into 5 zones. Practices are

listed from highest score to lowest score for each rating zone. The zones are “greatest strength”

(score of 8-10), “high strength” (score of 6-7.5), “medium strength” (4-5.5), “lower

impact/evidence scored practices” (score of 2-3.5), “lowest impact/evidence scored practices”

(score of 0-1.5). Practices near the bottom of one zone may be just as appropriate to list near the

top of the adjacent lower zone. Similarly, practices at the top of a zone may actually be more

comparable to those in the adjacent higher zone. The cut-offs between zones are somewhat

artificial, but allow a general and reasonable synthesis of the data on impact and evidence

supporting (or negating) the effects of the practice. Readers can be confident that practices that

fall in the highest zone do not belong in the lowest zone.

Chapter 58 summarizes the overall ratings for the “Research Priority” score, and provides

examples of types of research that may be helpful. Practices are categorized in 3 zones: “Further

Research Likely to be Highly Beneficial” (scores of 7 and higher), “Further Research Likely to

be Beneficial” (scores of 4 to 6.5 inclusive), and “Low Priority for Research” (below 4). The

chapter lists practices for each of the top two categories of research priority.
619

Chapter 57. Practices Rated by Strength of Evidence

After rating practices on a metric for potential impact, and on the strength of the

evidence, we grouped them into 5 categories (Tables 57.1-57.5). These categorizations reflect

the current state of the evidence. If a practice that addresses a highly prevalent or severe patient

safety target receives a low rating on the impact/evidence scale, it may be because the strength of

the evidence base is still weak due to lack of evaluations. As a result the practice is likely to

show up at a high level on the research priority scale. However, if the practice has been studied

rigorously, and there is clear evidence that its effectiveness is negligible, it is rated at the low

ends of both the “strength of the evidence” (on impact/effectiveness) scale and the “research

priority” scale.

For each practice listed in Tables 57.1 through 57.5, a designation for the cost and

complexity of implementation of the practice is included. The ratings for implementation are

“Low,” which corresponds to low cost and low complexity (eg, political, technical); “Medium,”

which signifies low to medium cost and high complexity, or medium to high cost and low

complexity; and “High,” which reflects medium to high cost and high complexity.

Several practices are not included in the tables because they were not rated. This set of

practices have long histories of use outside of medicine, but have not yet received enough

evaluations for their potential health care applications:

• Promoting a Culture of Safety (Chapter 40)

• Use of Human Factors Principles in Evaluation of Medical Devices (Subchapter 41.1)

• Refining Performance of Medical Device Alarms (eg, balancing sensitivity and

specificity of alarms, ergonomic design) (Subchapter 41.2)

• Fixed Shifts or Forward Shift Rotations (Chapter 46)

• Napping Strategies (Chapter 46)
620

Table 57.1. Patient Safety Practices with the Greatest Strength of Evidence Regarding their

Impact and Effectiveness

Chapter Patient Safety Target Patient Safety Practice Implementation

Cost/Complex

31 Venous thromboembolism (VTE) Appropriate VTE prophylaxis Low

25 Perioperative cardiac events in

patients undergoing noncardiac

surgery

Use of perioperative beta-blockers Low

16.1 Central venous catheter-related

bloodstream infections

Use of maximum sterile barriers during

catheter insertion

Low

20.1 Surgical site infections Appropriate use of antibiotic prophylaxis Low

48 Missed, incomplete or not fully

comprehended informed consent

Asking that patients recall and restate what

they have been told during informed

consent

Low

17.2 Ventilator-associated pneumonia Continuous aspiration of subglottic

secretions (CASS)

Medium

27 Pressure ulcers Use of pressure relieving bedding materials Medium

21 Morbidity due to central venous

catheter insertion

Use of real-time ultrasound guidance during

central line insertion

High

9 Adverse events related to chronic

anticoagulation with warfarin

Patient self management using home

monitoring devices

High

33 Morbidity and mortality in postsurgical and critically ill patientsVarious nutritional strategies Medium

16.2 Central venous catheter-related

bloodstream infections

Antibiotic-impregnated catheters Low
621

Table 57.2 Patient Safety Practices with High Strength of Evidence Regarding their Impact and

Effectiveness

Chapter Patient Safety Target Patient Safety Practice Implementation

Cost/Complex

18 Mortality associated with surgical

procedures

Localizing specific surgeries and procedures

to high volume centers

High (varies)

17.1 Ventilator-associated pneumonia Semi-recumbent positioning Low

26.5 Falls and fall injuries Use of hip protectors Low

8 Adverse drug events (ADEs) related

to targeted classes (analgesics, KCl,

antibiotics, heparin) (focus on

detection)

Use of computer monitoring for potential

ADEs

Medium

20.3 Surgical site infections Use of supplemental perioperative oxygen Low

39 Morbidity and mortality Changes in nursing staffing Medium

48 Missed or incomplete or not fully

comprehended informed consent

Use of video or audio stimuli Low

17.3 Ventilator-associated pneumonia Selective decontamination of digestive tract Low

38 Morbidity and mortality in ICU

patients

Change in ICU structure—active

management by intensivist

High

42.1 Adverse events related to

discontinuities in care

Information transfer between inpatient and

outpatient pharmacy

Medium

15.1 Hospital-acquired urinary tract

infection

Use of silver alloy-coated catheters Low

28 Hospital-related delirium Multi-component delirium prevention

program

Medium

30 Hospital-acquired complications

(functional decline, mortality)

Geriatric evaluation and management unit High

37.4 Inadequate postoperative pain

management

Non-pharmacologic interventions (eg,

relaxation, distraction)

Low
622

Table 57.3 Patient Safety Practices with Medium Strength of Evidence Regarding their

Impact and Effectiveness

Chapter Patient Safety Target Patient Safety Practice Implementation

Cost/Complex

6 Medication errors and adverse drug

events (ADEs) primarily related to

ordering process

Computerized physician order entry (CPOE)

and clinical decision support (CDSS)

High

42.4 Failures to communicate significant

abnormal results (eg, pap smears)

Protocols for notification of test results to

patients

Low

47 Adverse events due to transportation

of critically ill patients between health

care facilities

Specialized teams for interhospital transport Medium

7 Medication errors and adverse drug

events (ADEs) related to ordering and

monitoring

Clinical pharmacist consultation services Medium

13 Serious nosocomial infections (eg,

vancomycin-resistant enterococcus, C.

difficile)

Barrier precautions (via gowns & gloves;

dedicated equipment; dedicated personnel)

Medium

20.4 Surgical site infections Perioperative glucose control Medium

34 Stress-related gastrointestinal bleeding H2 antagonists Low

36 Pneumococcal pneumonia Methods to increase pneumococcal

vaccination rate

Low

37.2 Inadequate pain relief Acute pain service Medium

9 Adverse events related to

anticoagulation

Anticoagulation services and clinics for

coumadin

Medium

14 Hospital-acquired infections due to

antibiotic-resistant organisms

Limitations placed on antibiotic use Low

15.2 Hospital-acquired urinary tract

infection

Use of suprapubic catheters High

32 Contrast-induced renal failure Hydration protocols with acetylcysteine Low

35 Clinically significant misread

radiographs and CT scans by nonradiologists

Education interventions and continuous

quality improvement strategies

Low

48 Missed or incomplete or not fully

comprehended informed consent

Provision of written informed consent

information

Low

49 Failure to honor patient preferences for

end-of-life care

Computer-generated reminders to discuss

advanced directives

Medium (Varies)

9 Adverse events related to

anticoagulation

Protocols for high-risk drugs: nomograms

for heparin

Low
623

17.1 Ventilator-associated pneumonia Continuous oscillation Medium

20.2 Surgical site infections Maintenance of perioperative normothermia Low

26.2 Restraint-related injury; Falls Interventions to reduce the use of physical

restraints safely

Medium

26.3 Falls Use of bed alarms Medium

32 Contrast-induced renal failure Use of low osmolar contrast media Medium
624

Table 57.4 Patient Safety Practices with Lower Impact and/or Strength of Evidence

Chapter Patient Safety Target Patient Safety Practice Implementation

Cost/Complex

16.3 Central venous catheter-related

bloodstream infections

Cleaning site (povidone-iodine to

chlorhexidine)

Low

16.4 Central venous catheter-related

bloodstream infections

Use of heparin Low

16.4 Central venous catheter-related

bloodstream infections

Tunneling short-term central venous

catheters

Medium

29 Hospital-acquired complications (eg,

falls, delirium, functional decline,

mortality)

Geriatric consultation services High

37.1 Inadequate pain relief in patients with

abdominal pain in hospital patients

Use of analgesics in the patient with acute

abdomen without compromising diagnostic

accuracy

Low

45 Adverse events due to provider

inexperience or unfamiliarity with

certain procedures and situations

Simulator-based training Medium

11 Adverse drug events (ADEs) in drug

dispensing and/or administration

Use of automated medication dispensing

devices

Medium

12 Hospital-acquired infections Improve handwashing compliance (via

education/behavior change; sink technology

and placement; washing substance)

Low

49 Failure to honor patient preferences for

end-of-life care

Use of physician order form for lifesustaining treatment (POLST)Low

43.1 Adverse events due to patient

misidentification

Use of bar coding Medium (Varies)

10 Adverse drug events (ADEs) in

dispensing medications

Unit-dosing distribution system Low

24 Critical events in anesthesia Intraoperative monitoring of vital signs and

oxygenation

Low

42.2 Adverse events during cross-coverage Standardized, structured sign-outs for

physicians

Low

44 Adverse events related to team

performance issues

Applications of aviation-style crew resource

management (eg, Anesthesia Crisis

Management; MedTeams)

High

46 Adverse events related to fatigue in

health care workers

Limiting individual provider’s hours of

service

High
625

57.5 Patient Safety Practices with Lowest Impact and/or Strength of Evidence

Chapter Patient Safety Target Patient Safety Practice Implementation

Cost/Complex

23 Complications due to anesthesia

equipment failures

Use of pre-anesthesia checklists Low

42.3 Adverse events related to information

loss at discharge

Use of structured discharge summaries Low

22 Surgical items left inside patients Counting sharps, instruments and sponges Low

17.4 Ventilator-associated pneumonia Use of sucralfate Low

26.4 Falls and fall-related injuries Use of special flooring material in patient

care areas

Medium

43.2 Performance of invasive diagnostic or

therapeutic procedure on wrong body

part

“Sign your site” protocols Medium

26.1 Falls Use of identification bracelets Low

32 Contrast-induced renal failure Hydration protocols with theophylline Low

47 Adverse events due to transportation

of critically ill patients within a

hospital

Mechanical rather than manual ventilation

during transport

Low

16.4 Central venous catheter-related

bloodstream infections

Changing catheters routinely High

16.4 Central venous catheter-related

bloodstream infections

Routine antibiotic prophylaxis Medium
626
627

Chapter 58. Practices Rated by Research Priority

Further research on a number of practices would clarify a range of questions (eg, whether

the practice is effective, what aspects of a multi-faceted intervention matter the most, how best to

implement the practice). The conceptual framework for this categorization is described in

Chapter 56. In Table 58.1 and 58.2, the practices are grouped in zones: “research likely to be

highly beneficial,” and “research likely to be beneficial.” We also list, in the far-right column,

the practices’ categorization for “Strength of the Evidence” (as detailed above in Tables 57.1-

57.5). For presentation in this table, this category is simplified into a 1 (“highest strength of

evidence”) to 5 (“lowest strength of evidence”) which corresponds exactly to the groupings in

Tables 57.1-5. We list these here to allow the reader to compare and contrast the research

priority rankings with the evidence rankings. Practices that are not listed in either Table 58.1 or

58.2 may benefit from more research, but were not scored as highly as those included in these 2

lists.

Table 58.1 Further Research Likely to be Highly Beneficial

Chapter Patient Safety Target Patient Safety Practice Strength of

the Evidence

(1-5 Scale; 1

is highest)

20.4 Surgical site infections Perioperative glucose control 3

18 Mortality associated with surgical

procedures

Localizing specific surgeries and

procedures to high volume centers

2

20.3 Surgical site infections Use of supplemental perioperative oxygen 2

39 Morbidity and mortality Changes in nursing staffing 2

15.1 Hospital-acquired urinary tract

infection

Use of silver alloy-coated catheters 2

6 Medication errors and adverse

drug events (ADEs) primarily

related to ordering process

Computerized physician order entry

(CPOE) with clinical decision support

(CDSS)

3

14 Hospital-acquired infections due

to antibiotic-resistant organisms

Limitations placed on antibiotic use 3

20.1 Surgical site infections Appropriate use of antibiotic prophylaxis 1

31 Venous thromboembolism (VTE) Appropriate VTE prophylaxis 1

33 Morbidity and mortality in postsurgical and critically ill patientsVarious nutritional strategies (especially

early enteral nutrition in critically ill and

post-surgical patients)

1

37.1 Inadequate pain relief in patients

with abdominal pain in hospital

patients

Use of analgesics in the patient with acute

abdomen without compromising

diagnostic accuracy

4
628

12 Hospital-acquired infections Improve handwashing compliance (via

education/behavior change; sink

technology and placement; washing

substance)

4

9 Adverse events related to chronic

anticoagulation with warfarin

Patient self-management using home

monitoring devices

1

21 Morbidity due to central venous

catheter insertion

Use of real-time ultrasound guidance

during central line insertion

1

38 Morbidity and mortality in ICU

patients

Change in ICU structure—active

management by intensivist

2

32 Contrast-induced renal failure Hydration protocols with acetylcysteine 3

43.1 Adverse events due to patient

misidentification

Use of bar coding 4

27 Pressure ulcers Use of pressure relieving bedding

materials

1

20.2 Surgical site infections Maintenance of perioperative

normothermia

3

25 Perioperative cardiac events in

patients undergoing noncardiac

surgery

Use of perioperative beta-blockers 1

48 Missed or incomplete or not fully

comprehended informed consent

Use of video or audio stimuli 2

28 Hospital-related delirium Multi-component delirium prevention

program

2

7 Medication errors and adverse

drug events (ADEs) related to

ordering and monitoring

Clinical pharmacist consultation services 3

13 Serious nosocomial infections (eg,

vancomycin-resistant

enterococcus, C. difficile)

Barrier precautions (via gowns & gloves;

dedicated equipment; dedicated personnel)

3

9 Adverse events related to

anticoagulation

Anticoagulation services and clinics for

coumadin

3

48 Missed, incomplete or not fully

comprehended informed consent

Provision of written informed consent

information

3

49 Failure to honor patient

preferences for end-of-life care

Computer-generated reminders to discuss

advanced directives

3
629

9 Adverse events related to

anticoagulation

Protocols for high-risk drugs: nomograms

for heparin

3

26.3 Falls Use of bed alarms 3

11 Adverse drug events (ADEs) in

drug dispensing and/or

administration

Use of automated medication dispensing

devices

4
630

Table 58.2 Further Research Likely to be Beneficial

Chapter Patient Safety Target Patient Safety Practice Impact/

Evidence

Category

(1-5)

17.2 Ventilator-associated

pneumonia

Continuous aspiration of subglottic

secretions (CASS)

1

17.1 Ventilator-associated

pneumonia

Semi-recumbent positioning 2

26.5 Falls and fall injuries Use of hip protectors 2

30 Hospital-acquired

complications (functional

decline, mortality)

Geriatric evaluation and management

unit

2

47 Adverse events due to

transportation of critically ill

patients between health care

facilities

Specialized teams for interhospital

transport

3

34 Stress-related gastrointestinal

bleeding

H2-antagonists 3

37.2 Inadequate pain relief Acute pain service 3

15.2 Hospital-acquired urinary tract

infection

Use of suprapubic catheters 3

26.2 Restraint-related injury; Falls Interventions to reduce the use of

physical restraints safely

3

45 Adverse events due to provider

inexperience or unfamiliarity

with certain procedures and

situations

Simulator-based training 4

49 Failure to honor patient

preferences for end-of-life care

Use of physician order form for lifesustaining treatment (POLST)4

42.2 Adverse events during crosscoverageStandardized, structured sign-outs for

physicians

4

44 Adverse events related to team

performance issues

Applications of aviation-style crew

resource management (eg, Anesthesia

Crisis Management; MedTeams)

4

16.2 Central venous catheter-related

bloodstream infections

Antibiotic-impregnated catheters 1

17.3 Ventilator-associated

pneumonia

Selective decontamination of digestive

tract

2
631

42.4 Failures to communicate

significant abnormal results

(eg, pap smears)

Protocols for notification of test results

to patients

3

36 Pneumococcal pneumonia Methods to increase pneumococcal

vaccination rate

3

16.3 Central venous catheter-related

bloodstream infections

Cleaning site (povidone-iodine to

chlorhexidine)

4

16.4 Central venous catheter-related

bloodstream infections

Use of heparin 4

16.4 Central venous catheter-related

bloodstream infections

Tunneling short-term central venous

catheters

4

29 Hospital-acquired

complications (eg, falls,

delirium, functional decline,

mortality)

Geriatric consultation services 4

46 Adverse events related to

fatigue in health care workers

Limiting individual provider’s hours of

service

4

26.4 Falls and fall-related injuryies Use of special flooring material in

patient care areas

5

43.2 Performance of invasive

diagnostic or therapeutic

procedure on wrong body part

“Sign your site” protocols 5

42.1 Adverse events related to

discontinuities in care

Information transfer between inpatient

and outpatient pharmacy

2

48 Missed, incomplete or not fully

comprehended informed

consent

Asking that patients recall and restate

what they have been told during

informed consent

1

8 Adverse drug events (ADEs)

related to targeted classes

(analgesics, KCl, antibiotics,

heparin) (focus on detection)

Use of computer monitoring for

potential ADEs

2

24 Critical events in anesthesia Intraoperative monitoring of vital signs

and oxygenation

4

42.3 Adverse events related to

information loss at discharge

Use of structured discharge summaries 5
632
633

Chapter 59. Listing of All Practices, Categorical Ratings, and

Comments

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

6 Medication errors

and adverse drug

events (ADEs)

primarily related

to ordering

process

Computerized

physician order

entry (CPOE) with

clinical decision

support system

(CDSS)

High Medium1 Modest Medium High2 High

7 Medication errors

and ADEs related

to ordering and

monitoring

Clinical pharmacist

consultation

services

High Medium Modest3 Low High Low

8 ADEs related to

targeted classes

(analgesics, KCl,

antibiotics,

heparin) (focus on

detection)

Use of computer

monitoring for

potential ADEs

Medium Medium Robust4 Low Medium5 Low

9 Adverse events

related to

anticoagulation

Protocols for high

risk drugs:

nomograms for

heparin

Medium Medium6 Robust7 Medium Low Low

9 Adverse events

related to

anticoagulation

Anticoagulation

services and clinics

for coumadin8

High Medium Unclear Low Medium Low

9 Adverse events

related to chronic

anticoagulation

with warfarin

Patient selfmanagement using

home monitoring

devices

High High Robust Medium Medium9 High10

10 ADEs in

dispensing

medications

Unit-dosing

distribution system

Medium

11

Medium Unclear Low Low Low

11 ADEs in drug

dispensing and/or

administration

Use of automated

medication

dispensing devices

High Medium

12

Unclear Medium Medium

13

Low

12 Hospital-acquired

infections

Improved

handwashing

compliance (via

education/behavior

change; sink

technology and

placement;

High Medium

14

Unclear15 Low Low Low16
634

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

washing substance)

13 Serious

nosocomial

infections (eg,

vancomycinresistant

enterococcus, C.

difficile)

Barrier precautions

(via gowns &

gloves; dedicated

equipment;

dedicated

personnel)

High Medium

17

Robust Medium

18

Medium Low19

14 Hospital-acquired

infections due to

antibiotic-resistant

organisms

Limitations placed

on antibiotic use

High20 Medium Modest Medium

21

Low Low

15.1 Hospital-acquired

urinary tract

infection

Use of silver alloycoated cathetersHigh High Unclear22 Low Low Low

15.2 Hospital-acquired

urinary tract

infection

Use of suprapubic

catheters

High High Unclear

23

Medium High High

16.1 Central venous

catheter-related

blood infections

Use of maximum

sterile barriers

during catheter

insertion

Medium High Robust Low Low Low24

16.2 Central venous

catheter-related

blood infections

Antibioticimpregnated

catheters

Medium High Robust Low25 Low Low

16.3 Central venous

catheter-related

blood infections

Cleaning site

(povidone-iodine

to chlorhexidine)

Medium High Unclear Low Low Low

16.4 Central venous

catheter-related

blood infections

Changing catheters

routinely

Medium High Negligible

±

NA High High

16.4 Central venous

catheter-related

blood infections

Use of heparin Medium High Unclear Medium Low Low

16.4 Central venous

catheter-related

blood infections

Tunneling shortterm central venous

catheters

Medium High Unclear Low Low High

 

± Actually, studies show a detrimental effect of practice.
635

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

16.4 Central venous

catheter-related

blood infections

Routine antibiotic

prophylaxis

Medium Medium Negligible Medium Medium Low

17.1 Ventilatorassociated

pneumonia

Semi-recumbent

positioning

High Medium Robust26 Low Low Low

17.1 Ventilatorassociated

pneumonia

Continuous

oscillation

High High Robust27 Medium Medium Low

17.2 Ventilatorassociated

pneumonia

Continuous

aspiration of

subglottic

secretions (CASS)

High High Robust28 Low Low High29

17.3 Ventilatorassociated

pneumonia

Selective

decontamination of

digestive tract

High High Robust30 Medium

31

Low Low

17.4 Ventilatorassociated

pneumonia

Sucralfate High High Unclear High32 Low Low

18 Mortality

associated with

surgical

procedures

Localizing specific

surgeries and

procedures to high

volume centers

High Medium

33

Varies Medium Varies High

20.1 Surgical site

infections

Appropriate use of

antibiotic

prophylaxis

Medium

34

High Robust Medium

35

Low Low

20.2 Surgical site

infections

Maintenance of

perioperative

normothermia

High Medium

36

Robust Medium

37

Low Low

20.3 Surgical site

infections

Use of

supplemental

perioperative

oxygen

High Medium

38

Robust Low Low Low

20.4 Surgical site

infections

Perioperative

glucose control

High Medium Robust Medium Low High39

21 Morbidity due to

central venous

catheter insertion

Use of real-time

ultrasound

guidance during

central line

insertion

High High Robust40 Low41 Medium High

22 Surgical items left Counting sharps,

instruments,

Insuff. Low Not rated Not rated Low Low
636

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

inside patient sponges Info.42

23 Complications

due to anesthesia

equipment failures

Use of preoperative

anesthesia

checklists

Low43 Low Not rated Not rated Low Low

24 Critical events in

anesthesia

Intraoperative

monitoring of vital

signs and

oxygenation

Low44 Medium

45

Unclear46 Low Low Low

25 Perioperative

cardiac events in

patients

undergoing

noncardiac

surgery

Use of

perioperative betablockers

High High Robust Medium Low Low

26.1 Falls Use of

identification

bracelets

Medium Medium Negligible Low Low Low

26.2 Restraint-related

injuries; Falls

Interventions to

reduce the use of

physical restraints

safely

Medium Medium Unclear47 Medium Medium Low

26.3 Falls Use of bed alarms Medium Medium Unclear Low48 Medium

49

Low

26.4 Falls and fallrelated injuriesUse of special

flooring material in

patient care areas

Medium Low Not rated Not rated High Low

26.5 Falls and fall

injuries

Use of hip

protectors

Medium High Robust Medium Low50 Low51

27 Pressure ulcers Use of pressure

relieving bedding

materials

High High Robust52 Low High Low

28 Hospital-related

delirium

Multi-component

delirium

prevention

program

High Medium Robust Low Medium Low

29 Hospital-acquired

complications (eg,

falls, delirium,

functional decline,

mortality)

Geriatric

consultation

services

High High Varies53 Low Medium High
637

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

30 Hospital-acquired

complications

(functional

decline, mortality)

Geriatric

evaluation and

management unit

High High Modest54 Low Medium High

31 Venous

thromboembolism

(VTE)

Appropriate VTE

prophylaxis

High High Robust Medium Low Low55

32 Contrast-induced

renal failure

Use of low osmolar

contrast media

Medium High Robust Low High56 Low

32 Contrast-induced

renal failure

Hydration

protocols with

theophylline

Medium High Negligible Low Low Low

32 Contrast-induced

renal failure

Hydration

protocols with

acetylcysteine

Medium Medium

57

Robust Low Low Low

33 Morbidity and

mortality in postsurgical and

critically ill

patients

Various nutritional

strategies

High High Robust58 Medium Medium Low

34 Stress-related

gastrointestinal

bleeding

H2-antagonists Medium High Unclear Medium

59

Low Low

35 Clinically

significant

misread

radiographs and

CT scans by nonradiologists

Education

interventions and

continuous quality

improvement

strategies

Medium Medium Robust Low Low Low

36 Pneumococcal

pneumonia

Methods to

increase

pneumococcal

vaccination rate

Medium High Unclear60 Low61 Low Low

37.1 Inadequate pain

relief in hospital

patients with

abdominal pain

Use of analgesics

in patients with

acute abdomen

without

compromising

diagnostic accuracy

High Medium

62

Robust Medium Low Low63

37.2 Inadequate pain

relief

Acute pain service High Medium Robust64 Low65 Medium Low
638

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

37.4 Inadequate

postoperative pain

management

Nonpharmacologic

interventions (eg,

relaxation,

distraction)

High High Unclear Low Low Low

38 Morbidity and

mortality in ICU

patients

Change in ICU

structure—active

management by

intensivist

High Medium Robust66 Low Medium High

39 Morbidity and

mortality

Changes in nursing

staffing

High Medium

67

Varies Low High Low68

40 Any safety

problem amenable

to culture

Promoting a

culture of safety

Insuff.

Info.

**69 Varies High

41.1 Medical device

related adverse

events

Use of human

factors principles

in evaluation of

medical devices

Insuff.

Info.

**70 Varies High

41.2 Adverse events Refining

performance of

medical device

alarms (eg,

balancing

sensitivity and

specificity of

alarms, ergonomic

design)

High71 **72 Varies High

42.1 Adverse events

related to

discontinuities in

care

Information

transfer between

inpatient and

outpatient

pharmacy

High Medium Robust Low Medium

73

Low

42.2 Adverse events

during crosscoverage

Standardized,

structured signouts for physicians

Medium Low Not rated Not rated Low74 Low

42.3 Adverse events

related to

information loss at

discharge

Use of structured

discharge

summaries

Insuff.

Info

Low75 Not rated Not rated Low Low

42.4 Failures to

communicate

significant

abnormal results

Protocols for

notification of test

results to patients

Medium Medium Modest Low Low Low
639

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

(eg, pap smears)

43.1 Adverse events

due to patient

misidentification

Use of bar coding High76 Low Not rated Not rated Varies77 High

43.2 Performance of

invasive

diagnostic or

therapeutic

procedure on

wrong body part

“Sign your site”

protocols

High Low Not rated Not rated Low High

44 Adverse events

related to team

performance

issues

Application of

aviation style crew

resource

management (eg,

Anesthesia Crisis

Management;

MedTeams)

High78 Low Not rated Not rated Medium High

45 Adverse events

due to provider

inexperience or

unfamiliarity with

certain procedures

and situations

Simulator-based 

training

Insuff.

Info79

Medium

80

Unclear

81

Low Medium Low

46 Adverse events

related to fatigue

in health care

workers

Limiting individual

provider’s hours of

service

Insuff.

Info.

Medium Unclear Low High High

46 Adverse events

related to fatigue

in health care

workers

Fixed shifts or

forward shift

rotations

Insuff.

Info.

**82 Varies

83

Varies

46 Adverse events

related to fatigue

in health care

workers

Napping strategies Insuff.

Info.

**84 High85 Low

47 Adverse events

due to

transportation of

critically ill

patients between

health care

facilities

Specialized teams

for interhospital

transport

Medium Medium

86

Modest Low Medium Low
640

Ch. # Patient Safety

Target

Patient Safety

Practice

Impact Study

Strength

Effect Size Vigilance Cost Complexity

47 Adverse events

due to

transportation of

critically ill

patients within a

hospital

Mechanical

ventilation

Medium Medium Negligible Low Low Low

48 Missed,

incomplete or not

fully

comprehended

informed consent

Asking that

patients recall and

restate what they

have been told

during informed

consent

High Medium Robust Low Low Low87

48 Missed,

incomplete or not

fully

comprehended

informed consent

Use of video or

audio stimuli

High Medium Modest Low Low88 Low

48 Missed,

incomplete or not

fully

comprehended

informed consent

Provision of

written informed

consent

information

High Medium Unclear Low Low Low

49 Failure to honor

patient

preferences for

end-of-life care

Computergenerated

reminders to

discuss advanced

directives

High Medium Robust Low Medium

89

Low

49 Failure to honor

patient

preferences for

end-of-life care

Use of physician

order form for lifesustaining

treatment (POLST)

High Low Not rated Not rated Low Low90
641

Comments Section

1

 Medium strength of evidence for computerized physician order entry: although randomized

control trials have been conducted, findings from sophisticated “home grown” systems only 2-3

sites may not be fully generalizable. In addition, the impact of the practice on adverse events has

not been as well studied as for the non-clinical outcome, medication errors. 

2

 Cost of CPOE is substantially higher than for most other practices in the high cost category.

3

 The impact of clinical pharmacists consultation services may be less than that of CPOE due to

logistics of screening large volumes of orders to target those most prone to error or most

consequential.

4

 Estimate of effect size based on single study with limited target (only antibiotic treatments).

5

 Cost influenced by whether existing computer systems are used in pharmacy services.

6

 For nomogram protocols, study strength medium because the major concern (bleeding) is not

addressed in most studies.

7

 Effect size greater than 15% for surrogate markers; not bleeding or clot rate.

8

 Anticoagulation clinics: Both inpatient and outpatient venues studied, so some heterogeneity

among results.

9

 Self-management of warfarin (coumadin): on average the cost per patient is low, but the

aggregated cost is medium from the perspective of an insurer or integrated system.

10 Higher complexity of implementation because self-management practice displaces locus of

control out of institution and may engender debate over insurance coverage. Other countries

cover this practice, but it is currently not covered by Medicare in the United States.

11 Unit-dosing is a ubiquitous practice that has surprisingly little evidence of effectiveness;

evidence is old and mixed.

12 Study strength is affected because outcomes measured are not the major outcomes of interest -

ie, ADEs.

13 The implementation ratings are related to patient safety only, but note that institutions may

also implement this practice for cost-savings due to less drug loss and better inventory control.

14 Study design for handwashing compliance practices generally had short duration of follow-up;

no randomized control trials.
642

15 Unclear effect size due to mixed results and no clear pattern in a group of heterogeneous

practices.

16 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

17 There are a number of studies of barrier precautions, but most are Level 3 study designs so the

strength is not rated as “High.”

18 Potential decrease in provider interaction with patients may cause psychological, as well as

other, effects if care from clinicians is compromised.

19 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

20 Impact upgraded from “medium” to “high” rating because of public health impact of more

antibiotic-resistant pathogens.

21 Practice requires active, ongoing monitoring and input from infection control officers to make

sure proper drugs are prescribed. Also, vigilance includes need for institution-wide monitoring of

pathogens.

22 The effect size of using silver alloy catheters is unclear: a well-done meta-analysis is positive,

showing decrease in bacteriuria, but more recent results of possibly better designed individual

studies are mixed regarding benefit. Also, the actual strength of the link, however intuitive,

between bacteriuria and clinically significant urinary tract infection is unclear.

23 Effect size of using suprapubic catheters is unclear because of some heterogeneity in studies.

Results are generally positive, but no meta-analysis yet conducted. In addition, the effect on

outcome of clinically significant urinary tract infections is also unclear.

24 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

25 With antibiotic-impregnated catheters made with minocycline, there is the theoretical risk of

increased antibiotic resistance.

26 Pneumonia outcome was significantly reduced, but mortality was not.

27 Meta-analysis of 6 randomized controlled trials showed significant and large relative risk

reduction, but 2 other randomized controlled trials showed no impact.

28 Benefit observed in prevention of ventilator-acquired pneumonia; no established benefit for

mortality.
643

29 High complexity for implementation since it requires retraining for a new practice.

30 Most benefit in reducing pneumonia and mortality occurs when both IV and topical

decontamination are used. Topical (by itself) only reduces ventilator-associated pneumonia. 

However, topical carries less potential for harm (ie, antibiotic resistance).

31 Medium vigilance for harm because of public health concerns due to possible increase in

antibiotic resistance. The Center for Disease Control and Prevention (CDC) and the American

Thoracic Society (ATS) both recently reviewed this topic and did not recommend this practice.

32 If sucralfate were used because of its possible effect on reducing risk of ventilator-acquired

pneumonia, it would displace a practice that has more established benefit for GI bleeding (H2

blockers).

33 The study strength for localizing care to high volume centers is evaluated across a range of

practices. There are large variations in evidentiary base across specific practices. Evidence is not

structured to determine effect on patient safety. Although the literature includes possible

benchmarks/thresholds for volume levels for specific procedures, the evidence is related more to

quality enhancement than to improvements in patient safety.

34 Relatively high current utilization of practice reduced impact by one level.

35 Vigilance is required to monitor antibiotic overuse to prevent negative public health effects.

36 Study strength is rated as medium because randomized clinical trial data only applies to one

disease process, although may be generalizable.

37 Medium vigilance for harm: although not studied, for certain cohorts the practice may be

detrimental.

38 Study strength is rated as medium because randomized clinical trial data only applies to one

disease process, although may be generalizable.

39 Tight perioperative glucose control requires major shift in practice style, increased vigilance,

more coordination between nurses and physicians, and perhaps new policies regarding nursing

care for diabetics.

40 Effect size high, but more impressive decrease in “failed insertion attempts” than in more

clinically relevant complications. Also, there is some heterogeneity in study results, and there

are two different technologies assessed (plain ultrasound vs. US with doppler), and the results

vary.

41 Theoretical risk that additional manipulation/handling could increase infection risk; also

concern regarding impact on providers’ abilities to place catheters emergently when ultrasound

guidance is not available.
644

42 Insufficient information about retained sponges: the event is highly concerning and often

morbid when occurs, but the only data on frequency are from case reports.

43 Low potential impact because anesthesia complications are already so uncommon; also

difficult to determine impact of current use of some version of this practice (eg, low opportunity

possible due to current utilization).

44 Low potential impact because anesthesia complications are already so uncommon; also

difficult to determine impact of current use of some version of this practice (eg, low opportunity

possible due to current utilization).

45 Although there has been a very large randomized trial of pulse oximetry, other studies covered

additional aspects of intraoperative monitoring and were generally of lower study design quality.

46 Pulse oximetry study showed no benefit, but major potential methodologic problems, such as

secular trends. Complications that monitoring are designed to find are very unusual, so even a

large trial may have been under-powered to detect important effects. 

47 Because the patient safety target is reduction of unnecessary restraints, there are multiple

outcomes of interest. Although reducing unnecessary restraints does not seem to increase the risk

of falls, it raises other concerns regarding disconnected IVs, elopement risk, etc., which have not

been fully evaluated.

48 Probably low, as categorized, but there is a theoretical risk that patients will not receive as

much attention from nurses and other providers.

49 Medium cost based on relatively widespread implementation of bed alarms required to impact

all patients who may potentially benefit. May also impact nursing workload and staffing needs.

50 Possibly higher cost if large numbers of patients would benefit from wearing hip protectors.

There is also the question of whether these costs are borne by system/insurers or patients

themselves.

51 Implementation complexity in the hospital may be low, but implementation outside of the

hospital might involve large educational campaign directed at patients who could benefit from

practice.

52 Studies compare a variety of special bedding materials to standard beds. Effect size for one

special bed option versus another is not known. Unclear which particular surface works best.

53 Effect size varies since heterogeneous outcomes, perhaps in part related to the variety of

interventions, some of which involved both inpatient and outpatient components.

54 Effect size varies due to heterogeneous results, which depend in part on the outcomes of

interest (ie, functional outcomes vs. mortality).
645

55 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

56 Total cost, of course, depends on the extent of utilization (eg, all patients versus only targeted

patients). Cost-effectiveness analyses demonstrate the importance of targeting appropriate

patients.

57 Outcome is level 2, only one study for N-acetylcystine.

58 Varies according to specific nutritional support practice. Robust findings for early enteral

nutrition in critically ill and post-surgical patients.

59 Vigilance for harm is medium because of potential risk of increasing ventilator-associated

pneumonia, and also because of possible overuse since high-risk groups are now better defined.

60 Depends on specific intervention; standing orders have the highest effectiveness.

61 Harm concern low, except one recent study (see Chapter 36) showed trend toward harm in

HIV-positive patients.

62 Although some studies were randomized control trials, they did not look at all clinically

relevant outcomes to ensure that practice was safe. Under-powered to assess whether diagnostic

capability not impaired.

63 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

64 Only studied for post-operative pain; may not apply more generally.

65 Some speculation that care may be fragmented when applied broadly, beyond post-operative

patients.

66 Some of the positive results may be attributable to factors other than the intervention. Concern

about underlying population changing (eg, secular trends).

67 Study strength is medium despite a number of studies, because of variation in practices (eg,

various measures of nurse staffing, models of care). Chapter was designed to generalize across

practices regarding nursing structure versus outcomes; evidence is not structured to tell effect on

patient safety, and there are no benchmarks/thresholds for nurse staffing levels.

68 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.
646

69 Most evidence available outside of medicine; study strength not rated. These practices, drawn

largely from non-health care industries, were not fully rated because of their unique nature and

their relatively small evidentiary base in the health care literature.

70 Most evidence available outside of medicine; study strength not rated. These practices, drawn

largely from non-health care industries, were not fully rated because of their unique nature and

their relatively small evidentiary base in the health care literature.

71 Although alarms are ubiquitous in the hospital, it is unclear how many adverse events might

be improved by improvements in alarm systems.

72 Most evidence available outside of medicine; study strength not rated. These practices, drawn

largely from non-health care industries, were not fully rated because of their unique nature and

their relatively small evidentiary base in the health care literature.

73 Costs are shared among a variety of payors including outpatient pharmacy.

74 Cost would vary based on interventions considered—some low-tech, paper-based, or pocket

computers; higher cost for full-scale computerized systems.

75 Although one randomized trial performed, the outcomes reported were only indirectly related

to patient safety outcomes.

76 Somewhat unclear, but errors due to misidentification can be grave.

77 Cost varies based on specific system and level of implementation.

78 Impact is a function of how widely the practice can be used (ICU vs. ward teams vs. operating

room).

79 Insufficient information outside of anesthesia about volume of human factors errors amenable

to training approaches.

80 Limited studies with small numbers of participant and with different simulators lead to

concerns about generalizability.

81 Effect unclear since few studies with comparable simulators, and evaluated with mostly Level

3 outcomes.

82 Most evidence available outside of medicine; study strength not rated. These practices, drawn

largely from non-health care industries, were not fully rated because of their unique nature and

their relatively small evidentiary base in the health care literature.

83 Fixed shift may be more costly and difficult to implement than forward rotation.
647

84 Most evidence available outside of medicine; study strength not rated. These practices, drawn

largely from non-health care industries, were not fully rated because of their unique nature and

their relatively small evidentiary base in the health care literature.

85 Restructuring patient care to allow for napping while minimizing discontinuities could be

expensive.

86 Study strength is borderline-medium with three Level 3 studies.

87 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.

88 Cost for video disks – assumes that off-the-shelf products exist for common procedures; would

be higher if an institution has to build its own systems.

89 Cost would be lower for health care organizations that already rely on computers for care

management.

90 Rated as low, but this practices requires behavior change on the part of the provider.

Therefore, it may be more difficult to implement because its success largely rests on education

(see Chapter 54) and acceptance.
648
649

Appendix: List of Contributors

Editorial Board

Kaveh G. Shojania, MD

Assistant Professor

Department of Medicine

University of California, San Francisco

San Francisco, CA

Bradford W. Duncan, MD

AHRQ Patient Safety Fellow

Center for Primary Care & Outcomes

 Research

Stanford University

Stanford, CA

Kathryn M. McDonald, MM

Executive Director

Center for Primary Care & Outcomes

 Research

Stanford University

Stanford, CA

Robert M. Wachter, MD

Professor and Associate Chairman

Department of Medicine

University of California, San Francisco

San Francisco, CA
650

Contributors

Joseph V. Agostini, MD

Robert Wood Johnson Clinical Scholar

Yale University School of Medicine

New Haven, CT 

Chapters 26-30

Andrew D. Auerbach, MD, MPH

Assistant Professor of Medicine

University of California, San Francisco

San Francisco, CA

Chapters 18-20, 22-25

Dorothy I. Baker, PhD, RNCS

Research Scientist, Chronic Disease Epidemiology

Department of Epidemiology and Public Health

Associate Director, Claude Pepper Older Americans

Independence Center

Yale University School of Medicine

New Haven, CT

Chapters 26-30

David W. Bates, MD, MSc

Associate Professor of Medicine

Harvard Medical School

Chief, Division of General Internal Medicine

Brigham and Women's Hospital

Boston, MA

Chapters 6-9, 41, 42, 45, and 46

Sidney T. Bogardus, Jr., MD

Assistant Professor of Medicine

Yale University School of Medicine

Medical Director, Adler Geriatric Assessment

Center

Yale-New Haven Hospital

New Haven, CT 

Chapters 26-30

Erica Brownfield, MD

Assistant Professor of Medicine

Emory University School of Medicine

Grady Memorial Hospital

Atlanta, GA

Chapter 37

Harold R. Collard, MD

Fellow in Pulmonary & Critical Care Medicine

University of Colorado Health Sciences Center

Denver, CO

Chapter 17

Lorenzo Di Francesco, MD

Assistant Professor of Medicine

Emory University School of Medicine

Department of Medicine

Grady Memorial Hospital

Atlanta, GA 

Chapter 32

Daniel D. Dressler, MD

Instructor of Medicine

Emory University School of Medicine

Hospital Medicine Fellow

Grady Memorial Hospital

Atlanta, GA

Chapter 34

Bradford W. Duncan, MD

AHRQ Patient Safety Fellow

Center for Health Policy

Center for Primary Care & Outcomes Research

Stanford University

Stanford, CA 

Chapters 45 and 46
651

Sharon K. Inouye, MD, MPH

Associate Professor of Medicine

Yale University School of Medicine

Investigative Medicine Program

New Haven, CT

Chapters 28 and 29

Salim D. Islam, MD

Assistant Clinical Professor

Department of Anesthesia and Perioperative Care

University of California, San Francisco

San Francisco VA Medical Center

San Francisco, CA 94121

Chapters 23 and 24

Ashish K. Jha, MD

Assistant Professor of Medicine

University of California, San Francisco

Division of General Internal Medicine

San Francisco VA Medical Center

San Francisco, CA

Chapters 45 and 46

Rainu Kaushal, MD, MPH

Instructor in Medicine

Harvard Medical School

Division of General Internal Medicine

Brigham and Women’s Hospital

Boston, MA

Chapter 6 and 7

Jennifer Kleinbart, MD

Assistant Professor of Medicine

Emory University School of Medicine

Atlanta, GA

Chapter 31

Sunil Kripalani, MD

Instructor of Medicine

Emory University School of Medicine

Division of General Medicine

Grady Memorial Hospital

Atlanta, Georgia

Chapter 35

Ebbing Lautenbach, MD, MPH, MSCE

Assistant Professor of Medicine and

Epidemiology

University of Pennsylvania School of Medicine

Hospital Epidemiologist, Presbyterian Medical

Center

Philadelphia, PA

Chapters 12-14

Susana B. Martins, MD, MSc

Fellow, Institute for Health Policy Studies

University of California, San Francisco

Foster City, CA

Chapter 47
652

Harvey J. Murff, MD

Fellow, Division of General Internal Medicine

Brigham and Women's Hospital

Boston, MA

Chapters 23, 41 and 42

Michael D. Murray, PharmD, MPH

Professor of Pharmacy

Purdue University School of Pharmacy

Scientist, Regenstrief Institute for Healthcare

Regenstrief Health Center, Sixth Floor

Indianapolis, Indiana

Chapters 10 and 11

David B. Nash, MD, MBA

Associate Dean and Director

Office of Health Policy and Clinical Outcomes

Thomas Jefferson University

Philadelphia, PA

Chapters 40, 44, 48 and 50

Steven Z. Pantilat, MD

Assistant Professor of Medicine

University of California, San Francisco

Project on Death in America Faculty Scholar

San Francisco, CA

Chapter 49

Laura T. Pizzi, PharmD

Project Director

Office of Health Policy and Clinical Outcomes

Thomas Jefferson University

Philadelphia, PA

Chapters 40, 44, 48 and 50

Jeffrey M. Rothschild, MD, MPH

Instructor in Medicine

Harvard Medical School

Division of General Medicine

Brigham and Women's Hospital

Boston, MA

Chapters 21 and 38

Kimberly Rask, MD, PhD

Assistant Professor of Medicine and Health Policy

Emory University Schools of Medicine and Public

Health

Grady Memorial Hospital

Atlanta, GA

Chapters 31,34, and 35

Sanjay Saint, MD, MPH

Assistant Professor of Medicine

Director, Patient Safety Enhancement Program

University of Michigan School of Medicine

Research Scientist

Ann Arbor VA Health Services Research &

Development Field Program

Ann Arbor, MI

Chapters 15-17
653

Jean Ann Seago, PhD, RN

Assistant Professor of Nursing

University of California, San Francisco

Research Fellow

Center for California Health Workforce Studies

San Francisco, CA

Chapter 39

Kaveh G. Shojania, MD

Assistant Professor

Department of Medicine

University of California, San Francisco

San Francisco, CA

Chapters 4, 5, 9, 10, 43, and 47

Robert Trowbridge, MD

Clinical Instructor

Department of Medicine

University of California, San Francisco

San Francisco, CA

Chapters 51-55

Robert M. Wachter, MD

Professor and Associate Chairman

Department of Medicine

University of California, San Francisco

Chief of the Medical Service

Moffitt-Long Hospitals

San Francisco, CA

Chapter 55

Heidi Wald, MD

Assistant Professor in Medicine

University of Pennsylvania

Director, Penn Hospital Care Group

Hospital of the University of Pennsylvania

Philadelphia, PA

Chapters 4,5 and 43

Scott Weingarten, MD, MPH

Associate Professor of Medicine

University of California, Los Angeles

Director, Health Services Research

Cedars-Sinai Health System

Beverly Hills, CA

Chapters 51-54

Mark V. Williams, MD

Associate Professor of Medicine

Director, Hospital Medicine Unit

Emory University School of Medicine

Medical Director, Center for Clinical

Effectiveness

Grady Memorial Hospital

Atlanta, GA

Chapters 31-35

Neil Winawer, MD

Assistant Professor of Medicine

Emory University School of Medicine

Grady Memorial Hospital

Atlanta, GA

Chapter 33
654
655

Index

abdominal pain, acute

analgesics for, 399

analgesics studies, 400, 401

academic detailing for modifying physician behavior, 601,

603

accreditation methods to promote patient safety practices,

613

accreditation organizations, 609

active error, 51

acute pain services

described, 403

studies, 404, 406

acute spinal cord injury, VTE risk, 338

ADE detection

alert monitors, 79

computerized alert monitors, 79, 80

computerized systems, studies, 83

pharmacists, physicians, and, 79

physician response to alert monitors, 81

research needs, 82

ADEs

anticoagulants and, 87

CDSS and, 596

clinical pharmacists and, 71, 74, 75

computerized detection and alert systems, 79

described, 79

incident reporting, 42

information transfer between inpatient/outpatient

pharmacies, 475

prevalence, 71

advance directives for end-of-life care, 561, 565

Agency for Health Care Policy and Research (AHCPR),

399, 409

Agency for Healthcare Research and Quality (AHRQ)

acknowledgments, 21

patient advocacy, 575

patient safety, 607

patient safety improvement, 13

American Medical Association (AMA) Code of Medical

Ethics, 551

American Society for Health System Pharmacists (ASHP),

antibiotic administration, 221

American Society of Anesthesiologists (ASA), 259, 265,

410, 610

amphotericin, topical, 193

analgesics

acute abdominal pain management, 399

acute abdominal pain management studies, 400, 401

antiemetics for PCA, 407

research needs, 401

surgeon decision making , impact on, 401

anesthesia

body temperature and, 231

intraoperative monitoring and, 265

pre-anesthesia checklists, 259

simulator-based training, 516

anesthesia crisis resource management (ACRM), 508

anesthesia equipment checklists, 470

antibiotic resistance and pneumococcal vaccines, 392

antibiotics

benefits for controlling nosocomial infections, 143

practices to change use, 141

prescription errors, 142

prophylaxis for SSI, 221, 224, 226

urinary catheters and, 149

anticoagulation

ADEs and, 88

inpatient services, 94

outpatient clinics, 89

patient self-management, 89, 96

research needs, 91

antiemetics for pain management

described, 407

studies, 408

ASEPSIS, 232, 235

aspirin to prevent venous thromboembolism, 333

atelectasis, 185, 234

audit and feedback for modifying physician behavior, 601,

603

Australian Incident Monitoring Study (AIMS), 43, 45, 266

bacteremia and urinary catheters, 149

bacteriuria and urinary catheters, 149

bar coding

bedside scanning, 495

described, 491

medical recordkeeping, 493

medication dispensing and administration, 492

patient identification, 491

patient identification studies, 494, 495

research needs, 496

specimen handling, 492

barrier precautions, central venous catheter insertion

contamination reduction, 165

studies, 165

barrier precautions, VRE and C. difficile

compliance vs. specific intervention, 127

described, 127

further research, 130

list of, 127

studies, 129, 132, 135, 137

Baxter ATC-212 dispensing system, 111

bed alarms for fall prevention in older patients

described, 291

studies, 292, 293

bed sores, 156

beds or mattresses for pressure ulcer prevention

described, 301

studies, 302, 304

bedsores, 301

behavior-based safety interventions, 454

Best Medicine, The, 576

beta-blockers, perioperative

described, 271

research needs, 274

studies, 272, 276

bloodstream infections, catheter-related (CR-BSI)

defined, 163

risks, 164

bronchopulmonary secretions, 185

business community and patient safety, 609
656

calorimetry, 359

Candida species in catheter-related infections, 163

capnography, 267

cardiac disease, heparin and warfarin monitoring, 88

cardiac events

hypothermia, 231

reducing with beta blockers, 271

care delivery and interventions, nurse staffing and, 427,

431, 434

catheter colonization, 163

catheter related infections

central venous, 167

catheter-related bloodstream infection (CR-BSI)

antibacterial coatings and antiseptic agents, 169

CHG solutions and, 175

defined, 163, 164

intravenous antimicrobial use of, 179

catheter-related infections

bloodstream, 163

central venous, 164

urinary tract, 149

Centers for Disease Control and Prevention (CDC), 42,

164, 194, 608

antibiotic administration, 221

pneumococcal vaccines, 387

central venous catheters

antibacterial coatings or antiseptic agents, 169, 174

barrier precautions during insertion, 165

CHG and PI studies, 176, 178

chlorhexidine gluconate at the insertion site, 175

heparin and, 178

infection studies, 167

placement of, 245

prolonged use, infection risks and risk reduction, 165

research needs, 183

ultrasound guidance for insertion, 246

use of, 163

children, transporting, 540, 541, 542

chlorhexidine gluconate (CHG) solution

central venous catheter insertion, 175

compared to PI, studies, 176, 178

studies, 175

chlorhexidine/silver sulfadiazine-impregnated catheters

described, 169

studies, 169, 172, 174

circadian rhythm, 523, 528

clinical decision support systems (CDSS)

CPOE and, 595

described, 595

research needs, 599

safety practice promotion and implementation, 596

studies, 596, 597

clinical pharmacists

ADEs and, 71

ambulatory settings, study results, 73

consultation services, 72

impact on ADEs, studies, 75

outpatient settings, studies, 72

roles and activities, 71

closed ICU model, 417

Clostridium difficile (C. difficile)

antibiotic studies, 142, 143

antibiotics and, 141

barrier precaution studies, 129

barrier precautions and, 127

relationship to VRE, 128

research needs, 131, 144

SSI and, 222

transferability, 127

Cockpit Management Attitudes Questionnaire (CMAQ),

506

computerized discharge summaries, 483

computerized physician order entry (CPOE) with CDSS

CDSS described, 595

computerized sign-out program, 480, 483

continuous intravenous insulin infusion (CII) during

surgery, 238

continuous oscillation

described, 185, 187

studies, 187, 188

cranial computed tomography (CT), 377

Crew Resource Management (CRM)

aviation application vs. health care, 508

aviation environment, 505

described, 505

effectiveness measurement tools, 506

health care environment, 508

operating room environment, 509

peer monitoring, 509

research needs, 511

studies, 507, 510

critical incident technique, 41

critical pathways

described, 587

medical information dissemination, 587

research needs, 590

studies, 588, 591

cross-coverage, 480

Crossing the Quality Chasm: A New Health System for the

21st Century, 13

decubitus ulcers, 156, 301

deep vein thrombosis (DVT), 333, 341

delirium in older hospitalized patients

described, 307

geriatric consultation services and, 313

interventions, 307

research needs, 309

studies, 308, 310

diabetes

glucose control during surgery, 238

RCIN and, 349

diarrhea, C. difficile-associated, 128

direct mail patient notification, 487

discharge summaries

computerized, 483

research needs, 485

structured vs. unstructured format, 483

studies, 484, 485

disseminating medical information, 587

distal DVT, 333

domains, defined, 29

duplex ultrasonography, 335

durable power of attorney for health care (DPOA-HC), 561

educational techniques to modify physician behavior
657

described, 601

research needs, 604

studies, 602, 605

elastic stockings (ES) to prevent venous thromboembolism,

333

elderly

beta-blockers and, 273

delirium, preventing, 307

falling, preventing, 281

falls, preventing, 283

geriatric consultation services, 313

pneumococcal infections, 388

pneumococcal vaccines and, 389

pressure ulcers, preventing, 301

preventable deaths and functional decline, 324

embolism to the pulmonary vasculature, 333

end-of-life care

administrative initiatives, 565

advance directives, 565

described, 561

documenting patient preferences, 562

existing programs/contributions, 567

forms to promote implementation of patient preferences,

564

implementation of patient preferences, 562

improving physician/patient communication, 565

physician/patient communication, 563

preferences in outpatient setttings, 565

public education, 567

research needs, 568

enteral nutrition (EN)

immune-enhanced, 364

paths for administering, 359

studies, 361

environmental modifications to prevent delirium, 307

equipment, anesthesia, checklists for, 259

error mode prediction, 26

examination equipment, dedicated or disposable, as a

barrier precaution, 127, 137

extended-spectrum beta-lactamase (ESBL), 128, 143

falls in hospitalized and institutionalized older patients

bed alarms and, 291

geriatric consultation services and, 313

hip protectors and, 295

identification bracelets and, 284

interventions, list of, 283

physical restraints and, 287

problem description, 281

research needs, 283, 285, 289, 292, 294, 297

risk assessment, 282

risk factors, 281

special flooring and, 293

fatigue

lighting at work, 528

medical errors and, 523

medical therapies, 530

napping, 528

research needs, 530

shift limits and error reduction, 526

shift rotation and, 524

shift rotation, direction and speed, 527

sleep hygiene education, 528

studies, 526

fibrinogen leg scanning, 334

Flight Management Attitudes Questionnaire (FMAQ), 506

flooring, special, for fall prevention in older patients

described, 293

studies, 294, 295

Foley catheters, 149

Food and Drug Administration (FDA), 42, 51, 259, 262,

463, 493

gastroesophogeal reflux, 185

gastrointestinal bleeding

described, 369

nosocomial pneumonia and, studies, 373

research needs, 372

studies, 370

sucralfate and, 199

gentamicin, topical, 193

geriatric consultation services

described, 313

research needs, 316

studies, 314, 315, 318

geriatric evaluation and management (GEM) units

described, 313, 323

research needs, 326

studies, 324, 327

gloves/gowns as barrier precaution, 127

glucose control, perioperative

described, 238

research needs, 240

studies, 239, 241

surgical infections and, 238

government agencies and patient safety practices, 608

gram negative rods in catheter-related infections, 163

H2-receptor antagonists, 198, 369, 370, 373

hand disinfection, 119

handwashing

compliance difficulties, 119

relationship to infection, 119

research needs, 122

risk factors, 120

skin irritation to health care workers, 121

strategies to improve compliance, 121

studies, 120, 123

Health Care Financing Administration (HCFA)

medical errors, 607

physical restraints and, 288

pneumococcal vaccines, 287, 387

health literacy problem, 552

heart failure

ADEs and, 72

clinical pharmacists and, 73

heparin

about, 87

bleeding during therapy with, 88

central venous catheters and, 178

dosing and monitor errors, reducing, 87

LDUH/LMWH to prevent venous thromboembolism,

333

monitoring, 88

heparin nomograms

described, 87

PTTs and, 90
658

studies, 88, 92

high reliability theory, 26, 451

high-volume centers, localizing care to

Leapfrog Group’s efforts, 208

relationship to patient outcomes, 205

research needs, 208

studies, 206, 210

hip fractures

falls in older patients, 282

VTE risk in surgery, 336

hip protectors for fall prevention in older patients, 296, 298

hip replacement surgery, VTE risk, 336

histamine-2 receptor blocking agents (H2-receptor

antagonists)

described, 369

studies, 370, 373

VAP prevention, 198

hospitalists and end-of-life care, 566

human error identification, 26

human factors engineering (HFE)

anaesthesia equipment checklists, 470

described, 463

medical device alarms, 466

medical devices and errors, 463

research needs, 471

hydration protocols to prevent RCIN, 349

hygenic hand rub, 119

hypercholesterolemia, clinical pharmacists and, 73

hypertension, clinical pharmacists and, 73

hypoxemia and anesthesia, 267

identification bracelets for fall prevention in older patients

study, 285

using, 284

incident reporting

AIMS data vs. JCAHO data, 45

barriers to linking data with outcome, 46

critical incident monitoring, 41

event appropriateness, 43

intensive care units (ICUs), 42

JCAHO surveillance mandates, 43

medication errors and, 41

physician reporting, 45

research needs, 46

sentinel event alerts, 47

industries outside health care

aviation, 259, 505

behavior-based safety programs, 454

corporate cultures, 452

critical pathways, 587

disasters contributed to by fatigue, 524

incident reporting systems, 41, 42

safety cultures, 453

simulator training, 515

infection control officers, 608

information transfer, improving

abnormal results notification, 486

discharge summaries, 483

inpatient/outpatient pharmacies, 475

research needs, 478, 490

sign-out systems, 480

informed consent

asking patient to recall discussion information, studies,

555

form readability studies, 554

forms inadequacies, 553

legal and ethical obligations, 551

physician/patient discussion, studies, 554

procedural inefficiences in obtaining, 552

process, 551

research needs, 558

visual or auditory aids, studies, 556

written information to patients, studies, 557

Institute of Medicine (IOM) reports, 13, 205, 207, 210

intensive care units (ICUs)

incident reporting and, 42

intensivist model studies, 422

Leapgrog Group recommendations, 417

nutritional support for patients, 359

research needs, 420

structure model studies, 418, 419

structure models, 417

intensivist co-management ICU model, 417

intensivists in ICUs, 417

interhospital transportation of critically ill patients, 541,

542

interhospital transportation of critically ill patients, 539

intermittent pneumatic compression (IPC) to prevent

venous thromboembolism, 333

International Classification of Diseases (ICD-9) codes, 79

intrahospital transportation of critically ill patients, 539,

543

ischemia, myocardial, 267, 271

Joint Commission on the Accreditation of Healthcare

Organizations (JCAHO)

pain management guidelines, 399

patient safety advocacy, 609

physical restraint mandates, 288

root cause analysis mandate, 51

safety standards, 612

sentinel event alerts, 47

Sentinel Event Database, 43

surveillance mandate, 43

wrong-site surgery, avoiding, recommendations, 499

knee replacement surgery, VTE risk, 336

laparoscopic cholecystectomy training

complications with procedure, 214

learning curve, 213

research needs, 216

skills needed, 213

studies, 215

latent error, 51

Leapfrog Group

high-volume centers, 205

ICUs model recommendations, 417

methods to promote patient safety practices, 613

patient safety advocacy, 609

referral system, 208

learning curves for new procedures, 213

legal issues

end-of-life care, 561

informed consent, 551

legislation

methods to promote patient safety practices, 613
659

Natural Death Acts, 561

nursing issues, 429

Omnibus Budget Reconciliation Act of 1987, 288, 302

patient safety, 607

Patient Self-Determination Act (PSDA), 561

publication of performance data, 611

Lerner’s Consumer Guide, 576

lighting and fatigue, 528

LINE/LOS checklist, 506

living will for end-of-life care, 561

localizing care to high-volume centers, 205

low dose unfractionated heparin (LDUH) to prevent VTE,

333, 335

low molecular weight heparin (LMWH) to prevent VTE,

333, 335

machine-readable automatic identification (ID) systems

conventional wrist band use, 493

described, 491

medical record keeping, 493

medication dispensing and administration, 492

patient identification, 491

patient identification studies, 494, 495

research needs, 496

specimen handling, 492

malnutrition in hospitalized patients, 359, 363

McLaughlin dispensing system, 111

median sternotomy, 238

medical device alarms, 466

frequency reduction, 469

research needs, 470

source identification, 467

urgency ranking, 467

visual interfaces, 467

medical devices

design and development, 463

device evaluation, 465, 466

medical recordkeeping and bar codes, 493

medical records, patient access to, 576

medication dispensing and bar codes, 492

medication dispensing systems, automated

Baxter ATC-212 system, 111

described, 111

harmpotential, 113

machine-readable code, 111

McLaughlin system, 111

research needs, 114

studies, 111, 113, 115

unit-dose distribution systems and, 112

medication errors

clinical pharmacists impact on, studies, 75

dosage errors, 112

identification of ADEs, 41

information transfer between inpatient/outpatient

pharmacies, 475

studies, 106

time-constraints and, 101

unit-dose dispensing, 102

MedTeams behavior-based teamwork system, 509

melatonin supplementation for fatigue, 530

methicillin-resistant Staphylococcus aureus (MRSA), 128

minocycline/rifampin-coated catheters, 169

minocycline-coated urinary catheters, 149

misidentification, avoiding

bar coding, 491

wrong-site surgery, 499, 500, 501

wrong-site surgery, research needs, 502

monitoring, intraoperative

ASA standards, 268

described, 265

research needs, 267

studies, 266

napping, 528

National Quality Forum (NQF), 21

National Vaccine Advisory Committee, pneumococcal

vaccines, 387

Natural Death Acts, 561

nausea due to PCA, 407

neurosurgery, VTE risk, 337

non-radiologists

radiograph interpretations, 377

training, 378, 382

normal accident theory, 451

normothermia, perioperative

described, 231

studies, 232, 233

nosocomial infections

antibiotics and, 141

barrier precautions and, 127

handwashing and, 119

handwashing practices and, 120

pathogens other than VRE and C. difficile, 128

pneumonia and GI bleeding, 369

nurse staffing

availability studies, 430, 435

care delivery models, 434

care delivery studies, 431

care practices evaluated, 428

intervention studies, 431

measures, 434

nurse intervention and patient outcome studies, 441

organization models and patient outcome studies, 439

relationship of models to patient outcomes, 427

research needs, 432

studies, 430

unions and, 429

nutritional support practices

described, 359

studies, 360, 365

Occupational Safety and Health Administration (OSHA),

607

open ICU model, 417

opinion leaders for modifying physician behavior, 601, 603

opioids, 407

orientation techniques to prevent delirium, 307

oropharyngeal secretions, 190

osomolar iodinated contrast media to prevent RCIN, 349

oxygen, perioperative

described, 234

future research needs, 236

studies, 235, 236

pain management

abdomen, acute, 399

about, 399

acute pain services, described, 403
660

acute pain services, studies, 404, 406

antiemtics for PCA, 407

non-pharmacologic intervention studies, 410, 412

non-pharmacologic interventions, 409

patient education, 410

research needs, 411

palliative care programs, 566

patient advocacy

benefits, 575

improving non-compliance with medical advice and

treatment, 576

medical records, access to, 576

research needs, 577

patient classification systems (PCSs), 427

patient mobility to prevent delirium, 307

patient notification of abnormal results

direct mail, 487

problems and current methods, 486

research needs, 488

study, 487, 489

Patient Self-Determination Act (PSDA), 561

patient to nurse ratios, 428

peer monitoring, 509

percutaneous transluminal angioplasty, 271

pericatheter skin inflammation, 163

pharmacies

automated drug dispensing, 102

information transfer, 475, 476, 477, 479

pharmacologic measures to prevent venous

thromboembolism, 333

physical restraints for fall prevention in older patients

described, 287

studies, 288, 290

physician behavior, modifying

education techniques, research needs, 604

education techniques, studies, 602, 605

educational techniques, 601

practice guidelines, 582

pneumococcal infections

re-infection risks, 387

vaccines and, 387

pneumococcal vaccines

antibiotic resistance, 392

delivery method studies, 395

delivery methods, studies, 391

described, 387

effectiveness studies, 389, 390, 393

research needs, 392

pneumothorax, 247

POLST (Physician Orders for Life-Sustaining Treatment),

564, 570

polymixin, topical, 193

povidone-iodine (PI)

central venous catheter insertion, 175

compared to (CHG), studies, 176, 178

practice guidelines for modifying physician behavior

computer-based, 583

described, 581

research needs, 584

studies, 582, 583

pre-anesthesia equipment checklists

described, 259

research needs, 261

studies, 260, 262

pressure ulcers

in older patients, 301

research needs, 304

suprapubic catheters and, 156

professional societies and patient safety, 610

professional societies, to promote patient safety practices,

613

psychosocial support for pain management, 410

public reporting systems, 611

pulmonary embolization (PE), 333

pulse oximetry, 265, 267, 470, 610

Pyxis Medstations, 112

radiocontrast-induced nephropathy (RCIN)

described, 349

prevention practices, 349

prevention studies, 353, 354

studies, 350, 351

radiograph interpretation errors by non-radiologists

described, 377

digitized vs. film-based radiographs, 377

reducing, 378, 379, 382

research needs, 381

radiologists and non-radiologists

radiograph interpretations, 377

training, 378

reminder systems for modifying physician behavior, 601

renal failure, RCIN and, 349

report methodology

abstraction elements, 34

evidence review, 15

exclusion criteria, 31

exclusions, 16

inclusion criteria, 31

inclusions, 16

organization, 18

outcome measures, 32

review methodologies, 29

safety practice ratings, 619

safety practices evaluation, 33

safety practices organization, 29

search strategy, 30

study design hierarchy, 31

review methodologies, error-based, 29

rifampin-coated urinary catheters, 149

risk assessment to prevent falls in older patients, 282

root cause analysis (RCA)

industrial accidents, 51

JCAHO mandate, 51

process, 52

research needs, 55

studies, 53, 54

safety culture, promoting

accident theories, 451

behavior-based programs, 454

checklist of patient safety concepts, 457

methods, medical and non-medical, 452

research needs, 455

VHA initiative, 453

safety practice ratings

data inputs, 619
661

decision rules and judgment considerations, 621

goals, 619

impact and evidence overall rating, 622

rating process, 620

rating tables, 623

research priority overall rating, 623

safety practices

all practices, categorical ratings, and comments, 639

clinical vs. general issues in content, 17

definition and scope, 13, 29

further research likely to be beneficial, 636

further research likely to be highly beneficial, 633

greatest strength of evidence regarding their impact and

effectiveness, 626

high strength of evidence regarding their impact and

effectiveness, 627

hospital care and, 14

industries outside health care, 25

low strength of evidence regarding their impact and

effectiveness, 630

lowest strength of evidence regarding their impact and

effectiveness, 631

medium strength of evidence regarding their impact and

effectiveness, 628

organization of, 29

rated by strength of evidence, 625

research priority ratings, 633

selective digestive tract decontamination (SDD)

described, 193

studies, 194, 196

semi-recumbent positioning

described, 185

studies, 186, 188

Sentinel Event Database, 43

shift rotation and fatigue, 527

sign-out systems for cross-coverage

described, 480

research needs, 482

studies, 481, 483

silicone urethral catheters, 149

silver alloy catheters

bacteriuria reduction, 151

described, 149

simulator-based training

advantages, 515

anesthesia, 516

cardiology, 518

CRM and, 517

gastroenterology, 518

radiology, 517

research needs, 519

risks, 519

surgery, 517

sleep deprivation

lighting at work, 528

medical errors and, 523

medical therapies speed, 530

napping, 528

research needs, 530

shift limits and error reduction, 526

shift rotation and, 524

shift rotation direction and speed, 527

sleep hygiene education, 528

studies, 526

sponge, sharp, and instrument counts

described, 255

research needs, 256

studies, 256

staff cohorting as a barrier precaution, 127

staphylococci and catheter-related infections, 163

sternal wound infections, 238

streptococcus pneumoniae, 387

stress ulcers

H2-receptor antagonist therapy, 198

studies, 200, 202

subclavian-vein catheters, 246

subglottic secretions, continuous aspiration of

described, 190

diagram, 192

studies, 193

sucralfate

gastrointestinal bleeding reduction, described, 369

gastrointestinal bleeding reduction, studies, 370, 373

studies, 200, 202

VAP reduction, 198

suprapubic catheters

compared to standard catheters, 156

compared to urethral, studies, 159

placement of, 156

research needs, 157

studies, 157

surgical site infections (SSI)

antimicrobial prophylaxis and, 221

blood flow and body temperature, 231

glucose control for diabetics and, 238

normothermia and, 232

oxygen and, 234

research needs, 223, 233

studies, 222, 224, 226

surgical sponges and instruments, retained, 255

teicoplanin and central venous catheters, 179

teleradiology, 377

thromboembolism

heparin and warfarin monitoring, 88

preventions, 333

To Err is Human: Building a Safer Health System, 13, 25

tobramycin, topical, 193

total parental nutrition (TPN), 359, 361

training

end-of-life care, for physicians, 565

laparoscoopic cholecystectomy, 213

nurses, 428

radiograph interpretations, 378

simulator-based, 515

transesophageal echocardiography, 265

transfusion errors, 493

transport teams, 539

transportation of critically ill patients

about, 539

interhospital, 539

intrahospital transport, 539

manual vs. mechanical ventilation, studies, 546

transport teams vs. standard, studies, 545

transporting children, 540, 542
662

transurethral resection of the prostate, 157

trauma patients, VTE risk, 338

UCSF-Stanford Evidence-based Practice Center (EPC), 13

ultrasound guidance of central vein catheterization

described, 245

insertion success rates, 246

research needs, 249

studies, 246, 247, 250

unions and nurse staffing, 429

unit-dose dispensing

automated dispensing systems, 112

described, 101

dispensing variations, 101

JCAHO standards, 102

research needs, 105

safety targets, 102

studies, 103, 104, 106

urethral catheters

compared to suprapubic, 159

latex, 149

patient discomfort, 156

research needs, 157

silicone, 149

urethral strictures, 157

urinary catheters

impregnated with antibiotic, 149

silver alloy catheters, 149

studies, 150, 153

urinary tract infections (UTIs)

catheters and, 149

prevalence, 149

research needs, 151

usability testing, 465

vancomycin, systemic use with central venous catheters,

179

vancomycin-resistant enterococci (VRE)

antibiotic studies, 142, 143

antibiotics and, 141

barrier precaution studies, 129

barrier precautions and, 127

C. difficile relationship, 128

research needs, 131, 144

transferability, 127

venography, 334

venous thromboembolism (VTE)

described, 333

preventative measures, mechanical and pharmacologic,

342

preventions, 333

prophylaxis for surgical procedures and medical

conditions, 344

risk in general surgery, 335

risk in hospitalized medical patients, 339

risk in neurosurgery, 337

risk in orthopedic surgery, 336

risk reduction methods, 342

studies, 334

therapy factors, 337

urethral catheters and, 156

ventilation when transporting critically ill patients, 543,

546

ventilator-associated pneumonia (VAP)

continuous aspiration of subglottic secretions, 190

continuous oscillation, 185, 187

described, 185

patient positioning studies, 188

research needs, 195, 199, 203

SDD, 193

semi-recumbent positioning, 185, 186

sucralfate, 198

Veterans Health Administration (VHA), 453

vomiting due to PCA, 407

ward stock system, 102

warfarin

about, 87

dosing and monitoring errors, reducing, 87

monitoring, 88

self-management, studies, 89, 96

venous thromboembolism prevention, 333

warfarin nomograms, studies, 92

warming blankets for normothermia during surgery, 231

web-based health information, 16, 292, 455, 566, 576

web-based programs, 482

wrong-site surgery, avoiding

described, 499

research needs, 502

studies, 500, 501