Terrorism
and Disaster
Sarin

Sponsored for CME Credit by
Rush University Medical Center
Release Date: April 1, 2005
Expiration Date: March 31, 2007

WHAT
CLINICIANS
NEED TO
KNOW

errorism
Tand isaster
D
SERIESEDITORS
Rush University
Medical Center
Chicago, Illinois
Stephanie R. Black, MD*
Assistant Professor of Medicine
Section of Infectious Diseases
Department of Internal Medicine
Daniel Levin, MD*
Assistant Professor
General Psychiatry Residency Director
Department of Psychiatry
Gillian S. Gibbs, MPH*
Project Coordinator
Center of Excellence for Bioterrorism
Preparedness
Linnea S. Hauge, PhD*
Educational Specialist
Department of General Surgery

AUTHORS
Rush University
Medical Center
Chicago, Illinois

WHAT
CLINICIANS
NEED TO
KNOW

Uniformed Services University
Health Sciences
Bethesda, Maryland
David M. Benedek, MD, LTC, MC, USA
Associate Professor of Psychiatry
Steven J. Durning, MD, Maj, USAF, MC*
Associate Professor of Medicine
Thomas A. Grieger, MD, CAPT, MC, USN*
Associate Professor of Psychiatry
Associate Professor of Military &Emergency Medicine
Assistant Chair of Psychiatry for Graduate& Continuing Education
Molly J. Hall, MD, Col, USAF, MC, FS*
Assistant Chair & Associate Professor
Department of Psychiatry
Derrick Hamaoka, MD, Capt, USAF, MC, FS*
Director, Third Year Clerkship
Instructor of Psychiatry
Paul A. Hemmer, MD, MPH, Lt Col, USAF, MC*
Associate Professor of Medicine
Benjamin W. Jordan, MD, CDR, MC, USNR, FS*
Assistant Professor of Psychiatry

Stephanie R. Black, MD*
Assistant Professor of Medicine
Section of Infectious Diseases
Department of Internal Medicine

James M. Madsen, MD, MPH, COL, MC-FS, USA*
Associate Professor of Preventive Medicine
and Biometrics
Scientific Advisor, Chemical Casualty Care
Division, US Army Medical Research Instituteof Clinical Defense (USAMRICD), APG-EA

Daniel Levin, MD*
Assistant Professor
General Psychiatry Residency Director
Department of Psychiatry

Deborah Omori, MD, MPH, FACP, COL, MC, USA*
Associate Professor of Medicine
Michael J. Roy, MD, MPH, FACP, LTC, MC*
Associate Professor of Medicine
Director, Division of Internal Medicine
Jamie Waselenko, MD, FACP**
Assistant Professor of Medicine
Assistant Chief, Hematology/Oncology
Walter Reed Army Medical Center
Washington, DC

Guest Faculty
Ronald E. Goans, PhD, MD, MPH*
Clinical Associate Professor
Tulane University School of Public Health &Tropical Medicine
New Orleans, LA
Sunita Hanjura, MD*
Rockville Internal Medicine GroupRockville, MD
Niranjan Kanesa-Thasan, MD, MTMH*
Director, Medical Affairs & Pharmacovigilance
AcambisCambridge, MA
Jennifer C. Thompson, MD, MPH, FACP*
Chief, Department of Clinical Investigation
William Beaumont Army Medical Center
El Paso, TX

Faculty Disclosure Policy
It is the policy of the Rush University Medical
Center Office of Continuing Medical
Education to ensure that its CME activities
are independent, free of commercial bias
and beyond the control of persons or organizations with an economic interest in influencing the content of CME. Everyone who
is in a position to control the content of an
educational activity must disclose all relevant
financial relationships with any commercial
interest (including but not limited to pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject
matter of the presentation topic) within thepreceding 12 months If there are relationships that create a conflict of interest, thesemust be resolved by the CME Course
Director in consultation with the Office ofContinuing Medical Education prior to theparticipation of the faculty member in thedevelopment or presentation of course
content.
* Faculty member has nothing to disclose.
**Faculty disclosure: CBCE Speaker’s Corefor SuperGen.

SarinCASE AUTHOR: James M. Madsen, MD, MPH, COL, MC-FS, USA

ACCREDITATION & DESIGNATION STATEMENT
Rush University Medical Center is accredited by the Accreditation Council for Continuing
Medical Education (ACCME) to provide continuing medical education for physicians.
Rush University Medical Center designates this educational activity for a maximum of 1
credit of category 1 credit toward the AMA Physician’s Recognition Award. Each physician
should claim only those credits that he/she actually spent in the activity.
This CME activity was planned and produced in accordance with the ACCME Essentials.
CME credits are available free of charge through March 2007.

DISCLAIMER
This project was funded by the Metropolitan Chicago Healthcare Council (MCHC)
through a grant from the Health Resources and Services Administration (HRSA).
The opinions or assertions contained herein are the private views of the authors and are not
to be construed as official or as representing the opinion of Rush University Medical Center,
the Department of the Army, Department of the Navy, Department of the Air Force,
Department of Defense, MCHC or HRSA.
FDA Approved Drug and Devices Assurance Statement
In accordance with requirements of the FDA, the audience is advised that information presented in this continuing medical education activity may contain references to unlabeled orunapproved uses of drugs or devices. Please refer to the FDA approved package insert foreach drug/device for full prescribing/utilization information.

INSTRUCTIONS
The questions that appear throughout this case are intended as a self-assessment tool. For
each question, select or provide the answer that you think is most appropriate and compare
your answers to the key at the back of this booklet. The correct answer and a discussion of
the answer choices are included in the answer key.
Note: These self-assessment questions are not intended for CME credit. To apply for CME
credit, you must complete the CME Test at the back of this booklet and submit it according
to the directions provided.
In addition, a sign is provided in the back of this booklet for posting in your office or clinic.
Complete the sign by adding your local health department’s phone number.

Design and layout © 2005 Rush University Medical Center. The text contained herein falls under the U.S.
Copyright Act of 1976 as a “U.S. Government Work” and is therefore considered Public Domain Information,
however Rush University Medical Center reserves the right to copyright the design and layout of that information.

1

SarinCASE AUTHOR: James M. Madsen, MD, MPH, COL, MC-FS, USA

INTENDED AUDIENCEInternal medicine, family medicine, and emergency medicine physicians, and otherclinicians who will provide evaluation and care in the aftermath of a terrorist attack
or other public health disaster

LEARNING OBJECTIVES
Upon completion of this case, participants will be able to:• Explain the pathophysiology of nerve agents in terms of their effects oncholinergic neurotransmission.
• Describe the end-organ clinical effects of nerve agent poisoning.
• Compare the clinical presentation of victims exposed to sarin vapor to those
exposed to sarin liquid.
• Explain the use of decontamination and nerve-agent antidotes in the treatmentof sarin exposure and poisoning.

CASE PRESENTATION
On a cold Saturday evening in winter, a pregnant woman wearing an overcoat
buys a ticket at a large metropolitan multiplex for the second night of a highly anticipated movie featuring the newly introduced OlfacTree™ technology for allowing
moviegoers “the ultimate scents of realism” by experiencing odors relating to the film.
The film has also generated enormous controversy (and corresponding ticket sales) by
its moments of sudden and graphic terror, and in fact two moviegoers in separate cities
collapsed from apparent myocardial infarctions during a particularly gruesome andunexpected scene on the opening night.
The woman enters the large theater in plenty of time to take a seat in the middleof the room. She takes off her overcoat and places it underneath her seat. Eventually,
the theater is packed. Near the middle of the showing, a few minutes before a scary
scene set in a dim herbal shop, she excuses herself and walks to a women’s rest room,leaving her overcoat underneath her seat. In the rest room, she pulls a canister from apackage under her bulky sweater, forming the bulge that had made her look pregnant,and hides it just inside an inconspicuous but crucial ventilation duct that she had
investigated on previous visits to the multiplex. After exiting the building throughthe crowded lobby, she walks out to her van and sends a radio signal to the canister inthe vent and to a second canister hidden under her overcoat in the packed theater
but connected to a hose and a nozzle slightly protruding from a buttonhole in theovercoat. She then drives away without attracting attention.

2

Liquid flowing slowly from the canister in the theater ends up drenching theovercoat and eventually flowing down the floor to other rows of the theater. A few
annoyed moviegoers look behind them to see who spilled soda. Meanwhile, thecanister in the ventilation duct quietly releases a spray into the ventilation system
supplying four large theaters in the multiplex.
In the theater where the woman had been watching the movie, a few moviegoers
near the hidden canister quietly lose consciousness in their seats and attract no particular attention. Some people nearby feel tightness in their chests and some nausea,
but at this point in the movie these reactions are not unexpected. When one person
stands up, clutches his chest, and then falls over onto another moviegoer in the row
in front of him, nearby people try to aid him but also slump over. Other people inthat area try to run out of the theater but are in the middle of their rows and panic as
their egress is inhibited by others who are still seated, and, in some cases, unresponsive. A general panic ensues, with people screaming and heading toward the exits.
Popcorn and drinks are spilled throughout the theater, and some people slip on thespilled liquid. The lights come on in the room, and an announcement is made for an
orderly exit, but the screaming and fighting for the exits continue. Some collapse in
the rows and in the aisles, and several are trampled by other patrons.
By the time people spill into the main area of the multiplex, people from othertheaters are also starting to pour out of those rooms. Many are coughing and complaining of difficulty breathing. Many feel very weak and are crying and rubbing theireyes, which feel on fire. Many patrons are still sprawled across seats and on the floorsof several theaters in the building, and several are dead. The multiplex is evacuated,
but it is very cold outside and many moviegoers have left their coats inside the building. When questioned, many report having smelled a faint fruity odor that would nothave been out of place in the herbal shop portrayed in the scene that had been playing in the movie.
Upon their arrival, emergency personnel notify the receiving hospital to beprepared for casualties. The hospital activates its mass casualty plan, calling foradditional staff to be on-hand in the emergency department, wards, and intensive
care units.
COMMENT: The reported odor, irritation, weakness, salivation, collapse, and deaths suggest
a chemical agent. However, the presence of a chemical agent does not exclude the simultaneouspresence of a biological or radiological agent. In addition, these effects can all be psychological(including collapse and even death from vasovagal dysrhythmias or myocardial infarction) following
exposure to a relatively nontoxic substance or to a psychologically stressful situation.
Chemical warfare agents include four types of toxic agents1:• Respiratory tract irritants (pulmonary agents)• Asphyxiants (cyanides)• Vesicants (blister agents)• Cholinesterase inhibitors (nerve agents)
The reported effects, including sudden collapse and death, can occur with extremely high concentrations of any of these agents but would be most likely with either a nerve agent or a cyanide compound
and would be the least likely with a blister agent. The nature of odors is often used to try to identify
a chemical agent, but olfaction is very subjective and often misleading. For a review of factors thatdifferentiate nerve agent and other chemical agent effects, refer to Table 1.

3

Table 1. Features of Selected Major Chemical Exposures*
FeatureAsphyxiants

Cholinesterase Inhibitors

Respiratory Tract Irritants

Vesicants

Most likely agent
in accidental
releaseCarbon monoxide

Organic phosphorus pesticides

Chlorine and its derivatives,ammonia_

Most likely agent
in act of terrorism

CyanideSarin and VX

Chlorine, phosgene

Sulfur mustard

Hallmark

Tissue hypoxia in
cardiovascular systemand central nervous
system; usually,
absence of respiratory
tract irritation; no
increase in secretions

Cholinergic syndrome withpupil constriction (miosis) andincreased exocrine secretions,with or without fasciculations;increasing effects on central
nervous system with increasing exposure

Respiratory tract irritationand symptoms, usually more
prominent than irritation ofeyes and skin

Eye injuries and skinburns with vesicle formation, followed byrespiratory irritation and,in the case of exposure
to high concentration,systemic effects

Typical presentations
Mild symptoms
Headache, fatigue,
anxiety, irritability,
dizziness, nausea

Nose and throat irritation, sore
Miosis, dim vision, eye pain,rhinorrhea, irritability, headache, throat, cough, chest tightness,
eye irritation
chest tightness, sweating

Conjunctivitis, limited
erythema, epistaxis,
sore throat, coughCorneal damage, vesicles and bullae, nausea,
wheezing, stridor, laryngeal edema, acute lunginjuryModerate–to–serveresymptoms

Dyspnea, alteredmental status, cardiac
ischemia, syncope,coma, seizure

Laryngitis, wheezing, stridor,
Salivation, lacrimation, urination, defecation, gastrointestinal laryngeal edema, acute lunginjurycramping, and emesis, wheezing, muscle weakness, fasciculations, cognitive impairment,incontinence, coma, seizure

Hyperacute onset –sudden collapse

High concentrationsof cyanide or hydrogen sulfide and oxygen deficiency withina confined space

Exposures to VX or high-vapor
concentrations of other nerve
agents____Acute onset–
typically withinminutes to hours
after exposure

Most exposures toasphyxiant gases(carbon monoxide,
cyanide) or oxygen
deficiency

Vapor exposure, ingestion ofliquid form, or moderate –tolarge dermal exposure

Riot-control agents, irritants
highly and intermediately
water soluble (ammonia,
hydrochloric acid, chlorine)

Lewisite, phosgene
oxime, high concentrations of sulfur mustard

Delayed onset–
typically 4 to 6 hrs
after exposure

Low-to-moderateconcentrations of
substances thatmetabolize to primary
asphyxiant- methylene chloride (carbon
monoxide), acrylonitrile, and propionitrile(cyanide)

Limited exposure of skin to
droplets but not vapor

Poorly soluble gases (phosgene, nitrogen dioxide)

Sulfur mustard*Reprinted with permission from N Engl J Med.1

4

QUESTION 1
Which of the following signs and symptoms suggest a nerve agent rather than acyanide or pulmonary agent?
a. Increased secretions
b. Coughc. Headached. Sore throat
Reminder: You can find the Answer Key & Discussion on page 11.

COMMENT: The agent released from the canisters was sarin (o-isopropyl methylphosphonofluoridate), also known as GB. Sarin is a man-made chemical warfare agent classified as a nerve agent, themost toxic and rapidly acting of the known chemical warfare agents.2 Nerve agents are chemicals that
inhibit the enzyme acetylcholinesterase, preventing the breakdown of acetylcholine. Other nerve
agents include tabun (GA), soman (GD), cyclosarin (CF), and VX.
Sarin is a colorless, nonirritating, nearly odorless liquid with a faint perfume-like, floral, or fruity odor.
It can exist as a liquid and a vapor, with potential for direct contact with the eyes and mucous membranes, absorption into the eyes and skin, and inhalation.3 Eye irritation and coughing or choking may
be secondary to physiologic reactions to sarin (eg, miosis and bronchoconstriction) or may result from acaustic carrier chemical mixed with the sarin.

In the theater lobby and in the street, several moviegoers have difficulty finding
their way around, bumping into one another or into walls. Also, several complain ofchest tightness and difficulty breathing.

QUESTION 2
Which of the following statements is TRUE about the mechanism of action that
produces stumbling, chest tightness, and difficulty breathing after sarin exposure?
a. Stumbling is probably secondary to excess cholinergic stimulation of theconstrictor muscles of the irises, leading to miosis.
b. Chest tightness is probably a pre-cursor of sarin-induced damage to alveolarcapillary membranes and incipient pulmonary edema.
c. Because sarin causes weakness and then paralysis of the diaphragm, tightnessof the chest would not be expected and would imply the mixture of sarin witha pulmonary agent.
d. Stumbling is probably an early manifestation of damage to cerebellar pathways
involving balance from direct effects of sarin on the central nervous system.

5

COMMENT: Sarin and other nerve agents are anticholinesterases, chemicals that inhibit the
enzyme acetylcholinesterase (AChE). AChE is responsible for the breakdown of the cholinergic neurotransmitter acetylcholine (ACh) following its release from neurons in the body. This enzyme, AChE,
resides on the postsynaptic membranes of neurons, the post-junctional membranes of striated-muscle
and smooth-muscle cells, and on the post-junctional membranes of cells in exocrine glands stimulated
by ACh. Normally, AChE acts to break down ACh into choline and acetate, thereby terminating theeffect of ACh on the end-organ.
When nerve agents are introduced into the body, they bind to and inhibit AChE. When nerve agent
binds to cholinesterase, this enzyme can no longer hydrolyze ACh. ACh then accumulates at postsynaptic and post-junctional cholinergic receptors in cholinergic end-organs. Two major types of receptors for ACh exist:
1) Nicotinic receptors – present postsynaptically on the dendrites and cell bodies of neurons in autonomic ganglia and post-junctionally in myocytes of voluntary, or skeletal, muscle.
2) Muscarinic receptors – found postsynaptically in certain populations of neurons in the brain andpost-junctionally in smooth muscle and exocrine glands.
The excess of ACh causes cholinergic crisis and two general types of end-organ responses – hyperstimulation and eventual fatigue and failure. The effects of nerve agents are easily organized byorgan system according to the possible responses of the tissue. Thus, overstimulation of neurons in
the brain leads to seizures (clinically manifested as convulsions) and other derangements of neuralactivity, whereas fatigue and failure of the respiratory center in the medulla lead to central apnea.
Hyperstimulation of skeletal muscle causes twitching and fasciculations, whereas subsequent muscle
fatigue and failure are responsible for the weakness and paralysis (sometimes rigid, but usually flaccid)that can lead to respiratory arrest. Excess ACh postsynaptically in smooth muscle is responsible for
miosis, bronchoconstriction (including bronchospasm), and hyperperistalsis (manifested by nausea,
cramping, vomiting, and diarrhea). Hypersecretion of exocrine glands explains the lacrimation, rhinorrhea, salivation, and bronchorrhea that render a patient “wet all over.” This constellation ofsymptoms and signs is referred to as the cholinergic toxidrome, and its presence is
crucial in diagnosing nerve agent poisoning. See Table 2 for a summary of the clinical effects
on the nicotinic and muscarinic systems.
The heart is affected both directly by ACh released from the vagus nerves and also indirectly by AChinduced stimulation of neurons in sympathetic ganglia to release norepinephrine. Although cholinergic
crisis in animals usually leads to bradycardia, the heart rate in humans is unpredictable after nerve
agent poisoning and is more frequently elevated than depressed.

Table 2. The Clinical Effects of Overstimulated
Acetylcholine Receptors
Nicotinic

Muscarinic

6

Location of Receptor
Skeletal muscle

Clinical Effects
Fasciculations, muscle fatigue, weakness,paralysis, and respiratory arrest

Sympathetic ganglia and vagus nerve

Often tachycardia and hypertension

Exocrine glands

Lacrimation, rhinorrhea, salivation, bronchorrhea

Brain

Seizures

MedullaCentral apnea

Smooth muscle

Miosis, bronchoconstriction, hyperperistalsis

First responders wearing personal protective equipment arrive on the scene andinstruct the moviegoers to evacuate the building. Due to the cold weather, they are
escorted into the lobby of an adjacent office building. The moviegoers are instructed
to remove their clothing and place them in designated plastic bags. They are thenwashed thoroughly with soap and water and given clean robes to wear.

DUMBBELS is a useful mnemonicthat summarizes the muscarinic
effects on the body caused by nerve
agent exposure:
Diarrhea
Urinary Incontinence

COMMENT: When the identity of the agent is in doubt, all liquid must be considered to have

Miosis/Muscle Fasciculations

the potential to cause systemic toxicity via absorption and must be removed as quickly as possible. In
general, immediate management of a chemical casualty should involve ABCDD: Airway, Breathing,
Circulation, spot Decontamination, and administration of Drugs (specific antidotes) as available.

Bronchorrhea
Bronchospasm
Emesis

Prompt decontamination of liquid chemicals may be one of the simplest and yet mosteffective and important life-saving measures that can be taken at the scene of an
exposure. Because many toxic liquid chemicals may quickly penetrate the eyes, skin, and wounds,
decontamination of liquid must occur as soon as possible and should begin with removal of liquidsoaked clothing. Removing outer clothing can eliminate 85% to 90% of contamination.1
Decontamination is conducted by trained personnel wearing protective gear and includes washingwith soap and water. High concentrations of chemical decontaminants such as hypochlorite solutions(bleach) may damage the skin and lead to increased penetration of agent. Casualties pass from the
hot zone, or contaminated area, to the warm zone where they disrobe and wash before they pass tothe cold zone, or safe area. Ideally, decontamination should occur in the field, but the hospital mustalso be prepared to decontaminate, as many ambulatory patients will arrive on their own.
Decontamination must be accomplished as soon as possible, but even delayed decontamination can
prevent contamination of medical staff and facilities and prevent continued absorption from liquidremaining on the skin or clothes.

Lacrimation
Salivation

Factors that affect the decontamination process can include: weather (temperature and wind), numberof patients, triage category of patients, type of exposure (liquid vs. gas), severity of exposure, andavailable resources (trained personnel and equipment).

The arriving ambulance carries a cyanide antidote kit and three nerve agent
antidote kits, each with one autoinjector of atropine and one of 2-PAM chloride.
Just after the ambulance arrives, one of the passengers who has just left the multiplex
falls to the ground and stops breathing. The EMT administers the three nerve agent
antidote kits, but the patient does not respond.

QUESTION 3
What action should be considered after a patient fails to respond to three nerve
agent antidote kits?
a. Observe the patient for an hour in order for the antidote to take effect.
b. Administer an additional nerve agent antidote kit.
c. Administer the cyanide antidote kit.

COMMENT: Treatment of nerve agent casualties depends upon the severity and nature of exposure and effects.5 General supportive management includes attention to ABCs (airway, breathing,and circulation), decontamination (D), administration of supplemental oxygen, and observation. Mild
effects from exposure to vapor will resolve spontaneously and may not need antidotal treatment.

7

In general, effects from liquid exposure merit earlier and more aggressive treatment because of thelikelihood that the agent is still in transit through the skin.
Nerve agent antidotes (the second D in the ABCDDs) include an anticholinergic compound — atropine
sulfate, and an oxime — such as 2-pralidoxime chloride (2-PAM chloride). These two antidotes areoften packaged together in one kit as two autoinjectors (2 mg of atropine in one autoinjector and 600
mg of 2-PAM chloride in the other autoinjector) for intramuscular administration. Standard dosage
protocols are readily available from a variety of sources. Table 3 summarizes the clinical effects andtreatment for both vapor and liquid sarin exposure.
Atropine, a competitive inhibitor of ACh, works at muscarinic receptor sites but has no nicotinic effects
such as resolution of twitching or weakness. It can be thought of as a kind of “Pepto-Bismol®” that“coats” muscarinic end-organs and thereby prevents ACh end-organ effects. Following administrationof the first three autoinjectors, atropine should be repeated at five- to ten-minute intervals until muscarinic effects decrease. The use of additional 2-PAM chloride should be delayed for approximately anhour. The endpoints for atropine administration are a decrease in secretions and a decrease in airway
resistance. Nerve agent casualties seldom require more than a total of 20 mg of atropine. In contrast,
patients poisoned by organophosphate pesticides (which are also anticholinesterases) may require up
to one to two grams of atropine.
Pralidoxime chloride, or 2-PAM chloride, breaks the bond between the nerve agent molecule and the
AChE molecule. It can be visualized as a “2-PAM crowbar” that “pries” the nerve agent away fromthe enzyme. It is effective as long as the bond has not been modified by a process called aging, which
is analogous to the setting of glue. Once aging has occurred, 2-PAM chloride will be ineffective atregenerating AChE. The half-life of aging for sarin is approximately five hours. However, 2-PAM chloride should never be withheld out of concern that it may be administered too late after exposure.1
Although 2-PAM chloride acts at the bond between the nerve agent and AChE, its clinical effects aremostly nicotinic, that is, resolution of skeletal-muscle twitching, weakness, and paralysis. 2-PAM chloride is indicated for the treatment of poisoning by nerve agents and organophosphate pesticides. It is
not indicated for the treatment of poisoning by carbamate pesticides or anticholinesterases that do notcontain phosphorus.

In the emergency room waiting area, several of the ambulatory patients are complaining of pain in the eyes; physical examination reveals red eyes with tearing andmiosis. The emergency room physicians conduct a quick but thorough assessment of
the victims.
COMMENT: It is important to generate a differential diagnosis and to determine a presumptive
clinical diagnosis in terms of the agent involved. One must also estimate the agent dose, the state of
the agent in the environment, the route of exposure, whether effects are local or systemic, and whether
effects are likely to progress or to resolve with or without therapy. The state of the agent is important,because the time course of effects resulting from vapor and liquid exposure differ in clinically significant ways. Miosis can occur after both vapor and high-dose liquid exposure. Following removal fromthe agent, symptoms should not worsen if the exposure was to vapor only. However, if there was liquid
exposure, symptoms may develop or worsen as the absorbed agent makes its way through the skin.
Asking questions about the time course can provide a valuable estimate of the dose of agent, since
the length of the clinically asymptomatic period is usually inversely correlated with dose. Pertinent
questions for the past, present, and future include the following:
Past:
Duration of exposure? Time from exposure? Time of onset of symptoms?
Present: Is the patient getting better, getting worse, staying the same, or fluctuating in condition?
Future: What is the prognosis without therapy and with therapy?

8

Table 3. Summary of Nerve Agent Effects and Treatment*
Clinical Effects

Treatment• Uni- or bi-lateral miosis (pinpoint pupils)• Rhinorrhea (runny nose)• Shortness of breath (due tobronchoconstriction or bronchosecretions)• Combination of above• No treatment• 2 mg atropine if rhinorrhea or discomfort are severe• 2 mg atropine if mild or moderate; 4 mg if severe• Treat most severe effectModerate• Shortness of breath• 2-4 mg atropine, depending on severity; repeat 2 mg doses
every 5 minutes until improvement• Ventilate as needed via bag-valve-mask

Severe• Unconscious, convulsing, postictal, gasping
for air; effects in 2 or more systems• 6 mg atropine IM; repeat 2 mg doses every 5 minutes until
improvement• 1.8 g 2-PAM IM• Diazepam• Ventilate via bag-valve-mask• Suction airways if secretions are copious

Liquid exposure
Mild• Localized sweating; fasciculations• 2 mg atropine• 600 mg 2-PAM IM

Moderate• Gastrointestinal effects• 2 mg atropine• 600 mg 2-PAM IM

Severe• Same as for vapor• Same as for vapor

Vapor exposure
Mild*Adapted and reprinted with permission from Briggs and Brinsfield.6

QUESTION 4
A medical student in the emergency room is taking a history from one of thedecontaminated asymptomatic patients, when the patient suddenly gasps, falls
over, and starts convulsing on the floor. Which of the following conclusions
about this scenario is correct?
a. The patient is likely to have residual agent on his skin and needs to be
decontaminated again.
b. There is a probable pocket of residual sarin vapor, and the medical student
should immediately hold his or her breath and leave the area.
c. The collapse is likely to be from liquid nerve agent no longer on the skin.

COMMENT: The effects of nerve agents such as sarin depend in large measure on the state of
the agent in the environment, the route(s) of exposure, and whether the dose and the circumstancesof exposure cause local or systemic effects. Individual facial exposure to a very small amount of sarinvapor may cause miosis, rhinorrhea, salivation, mild bronchorrhea and bronchoconstriction, all fromlocal effects. As the dose increases, progression to systemic effects may occur, usually beginning withnausea. Local effects from vapor may occur almost immediately and usually do not worsen in severity
following removal from the agent. A small droplet of liquid on the skin will lead to localized twitching,fasciculations, and sweating. As the absorbed dose increases, systemic effects progressively develop;
progression, however, varies. A large dose of sarin may lead to sudden collapse with apnea and convulsions whether the exposure is from inhalation or percutaneous absorption. The difference is that9

sudden collapse from high vapor concentrations will occur within seconds, whereas sudden collapse froma significant amount of liquid on the skin will occur after a period of minutes to hours. The length of thelatent period after liquid exposure can help in estimating the absorbed dose; fatal doses of liquid agent
usually cause sudden effects after as little as 20 to 30 minutes. It is important to realize that early
appearance and successful treatment of vapor-induced effects do not exclude liquid exposure, and sarincasualties should be observed for 24 to 48 hours.

Several patients in the emergency room develop moderate to severe signs of nerve
agent exposure, and supportive care is continued. Antidotal treatment is also continued.

QUESTION 5
When should repeat intravenous or intramuscular doses of atropine bediscontinued?
a. When miosis resolves
b. When twitching and muscle weakness resolvec. When secretions and airway resistance decreased. When the heart rate rises above 110 beats per minute

Before discharge from the hospital, several patients ask about the likelihood of longterm complications from their exposure.

QUESTION 6
What would be the expected long-term complications for the victims described in
the case?
a. Most victims of acute exposure should recover without sequelae.
b. Subtle neurological effects have not been conclusively demonstrated
following recovery from nerve agent exposure.
c. Chronic organophosphate-induced delayed neurotoxicity (COPIDN), a“dying-back” neuropathy, has been seen after poisoning with organophosphate
insecticides but, curiously, has never been seen after nerve agent exposure.
d. “Intermediate syndrome,” with weakness of neck, limb, and respiratory
muscles, has occurred in a small number of nerve agent victims.

Ticket receipts show that a total of 1,233 patrons had been issued tickets to movies
showing in the multiplex at the time of the release of sarin. In addition, 32 theater
employees had been working that evening. A total of 6,430 patients, including movie
patrons, employees, first-responders, and hospital staff, were evaluated at several hospitals and clinics throughout the city. Of these, 433 had objective evidence of sarin exposure, including 15 emergency-response personnel and 7 hospital staff members. Of the
25 deaths attributed to the release, 8 were among those known to have been exposed toliquid sarin; one of these died after having been supported for 7 months on a ventilator,
without regaining consciousness. Autopsies indicated that 2 deaths had occurred outside
the theater in casualties who had been carried outside by other patrons and then left
on the sidewalk without attention to airway management; these victims might have10

survived had it not been for positional airway obstruction. Hypothermia was a contributor to a third death. Two middle-aged men were determined to have coronary-arterydisease that could have led to myocardial infarctions, although nerve agent release wasstill listed as the cause of death for these victims.
The morning after the incident, a local newspaper received a letter claiming
responsibility for the event and describing details that were later confirmed by forensic
investigation. Despite an intensive criminal and terrorist investigation, the perpetrators remain at large and their individual identities unknown. One year after the incident, 735 people, including many with no objectively demonstrated exposure, reportcontinued or recurrent largely nonspecific symptoms including weakness, lethargy,
memory problems, and flashbacks. Apart from hypoxic damage attributed to prolonged
apnea at the scene in 5 patients, the only demonstrated physiological abnormalities areminor memory deficits.

ANSWER KEY & DISCUSSIONQUESTION 1
Which of the following signs and symptoms suggest a nerve agent rather than acyanide or pulmonary agent?
a.
b.
c.
d.

Increased secretions
Cough
HeadacheSore throat

ANSWER: The correct answer is a. Increased secretions are a hallmark feature of nerve
agent exposure. A useful tools for remembering the classic presentation of sarin is the mnemonic
DUMBBELS (see sidebar on page 7). Cough and sore throat are typical presentations of pulmonary
and blister agents, while headache is a symptom of cyanides.

QUESTION 2
Which of the following statements is TRUE about the mechanism of actionthat produces stumbling, chest tightness, and difficulty breathing after sarin
exposure?
a. Stumbling is probably secondary to excess cholinergic stimulation of theconstrictor muscles of the irises, leading to miosis.
b. Chest tightness is probably a pre-cursor of sarin-induced damage toalveolar-capillary membranes and incipient pulmonary edema.
c. Because sarin causes weakness and then paralysis of the diaphragm, tightnessof the chest would not be expected and would imply the mixture of sarin witha pulmonary agent.
d. Stumbling is probably an early manifestation of damage to cerebellar pathways
involving balance from direct effects of sarin on the central nervous system.
ANSWER: The correct answer is a. Sarin, like other nerve agents, inhibits the enzyme thathydrolyzes ACh. Excess ACh, or cholinergic crisis, leads to miosis and therefore problems seeing,
especially at nighttime or in the dark. Chest tightness may occur from ACh-induced bronchospasm,
or cholinergic crisis leading to skeletal muscle overstimulation which may result in fatigue and failure. A

11pulmonary agent would cause alveolar-capillary membranes and incipient pulmonary edema.
Sarin can affect the central nervous system with high dose exposure, and seizures are the common
manifestation.

QUESTION 3
What action should be considered after a patient fails to respond to three nerve
agent antidote kits?
a. Observe the patient for an hour in order for the antidote to take effect.
b. Administer an additional nerve agent antidote kit.
c. Administer the cyanide antidote kit.
ANSWER: The correct answer is c. Weakness, nausea, lacrimation, salivation, and apnea, althoughpart of the cholinergic toxidrome and thus highly suggestive of nerve agent poisoning, may also beseen after exposure to pulmonary agents, blister agents, and especially cyanide. In fact, if a suspected
nerve agent fails to respond to initial administration of nerve agent antidotes, administration of thecyanide antidotes should be considered.4 The full standard initial antidotal treatment for a severely
poisoned nerve agent casualty is three nerve agent antidote kits plus a benzodiazepine, even if thecasualty has not yet begun to seize. Even if a fourth nerve agent antidote kit were available at thispoint, only the atropine autoinjector from that kit would be used; the use of additional 2-PAM chloride
should be delayed for approximately an hour.

QUESTION 4
A medical student in the emergency room is taking a history from one of thedecontaminated asymptomatic patients, when the patient suddenly gasps, falls
over, and starts convulsing on the floor. Which of the following conclusions
about this scenario is correct?
a. The patient is likely to have residual agent on his skin and needs to be
decontaminated again.
b. There is a probable pocket of residual sarin vapor, and the medical student
should immediately hold his or her breath and leave the area.
c. The collapse is likely to be from liquid nerve agent no longer on the skin.

ANSWER: The correct answer is c. This situation illustrates the importance of assessing whether
exposure was to vapor, liquid, or both. Whether exposure is to vapor or liquid, effects may be initiallyminor and progress, or they may be major and occur all at once. One useful difference is that effects
from inhalation of nerve agent vapor usually occur within seconds to minutes of exposure and once
present do not worsen once a casualty has been removed from exposure. However, liquid nerve agent
starts being absorbed through the skin soon after exposure, and effects are delayed while agent traverses the epidermis to reach the dermis, where it can be picked up by dermal blood vessels and thendistributed systemically. Skin decontamination will not remove agent already in transit through theskin and therefore will not prevent delayed effects from liquid. In this case, liquid exposure occurredfrom contact with liquid sarin in the theater and the surface of the skin was decontaminated several
minutes later, but severe systemic effects from the sarin that had already started to penetrate theskin were delayed until the agent had time to reach the circulation. This occurred, suddenly anddramatically, after the patient reached the emergency room.

12

QUESTION 5
When should repeat intravenous or intramuscular doses of atropine bediscontinued?
a. When miosis resolves
b. When twitching and muscle weakness resolvec. When secretions and airway resistance decreased. When the heart rate rises above 110 beats per minute
ANSWER: The correct answer is c. Atropine is a competitive inhibitor of ACh at muscarinic receptor sites and as such, counteracts only muscarinic effects such as secretions and bronchoconstriction.
Miosis is a muscarinic effect, but it occurs in a relatively isolated tissue that may not receive a full therapeutic dose of atropine from intramuscular or intravenous administration. In the absence of topicaladministration of atropine, miosis may take up to six weeks to resolve. The heart rate in nerve agent
poisoning may be low, high, or normal and is in fact more likely to be high than low. The heart rate isalways an important vital sign, but it should not be used either as an estimate of the severity of nerve
agent poisoning or as an endpoint for atropine administration.

QUESTION 6
What would be the expected long-term complications for the victims described in
the case?
a. Most victims of acute exposure should recover without sequelae.
b. Subtle neurological effects have not been conclusively demonstrated
following recovery from nerve agent exposure.
c. Chronic organophosphate-induced delayed neurotoxicity (COPIDN), a“dying-back” neuropathy, has been seen after poisoning with organophosphate
insecticides but, curiously, has never been seen after nerve agent exposure.
d. “Intermediate syndrome,” with weakness of neck, limb, and respiratory
muscles, has occurred in a small number of nerve agent victims.
ANSWER: The correct answer is a. Subtle and mostly subclinical chronic neurological effects
have been seen in low-dose exposures in nerve agent production facilities and in a few survivors of
acute high-dose exposures.7 Weakness of neck flexors and of proximal limb muscles with respiratory
depression characterized as “intermediate syndrome,” was seen after intentional ingestions of anticholinesterase insecticides in Sri Lanka, but this syndrome appears not to occur after nerve agent
exposure. “Ginger jake paralysis” from an anticholinesterase that contaminated Prohibition-era
whiskey was an example of a chronic axonal “dying-back” and demyelinating syndrome called chronicorganophosphate-induced delayed neurotoxicity (or COPIDN). This syndrome appears to be associatedwith an enzyme (neuropathic target esterase, or NTE) not affected by nerve agents. COPIDN after nerve
agent exposure has been documented in only a single case, the atypical case of a 51-year-old man
who inhaled sarin during the attack on the Tokyo subway system and who died 15 months later without regaining consciousness.8 Prompt diagnosis, repeated systematic assessments, supportive treatment, and specific antidotal treatment should lead to complete recovery without sequelae inmost acute victims of sarin exposure.

13

REFERENCES
1. Kales SN, Christiani DC. Acute chemical emergencies. N Engl J Med.
2004;350:800-808.
2. Centers for Disease Control and Prevention (CDC). Facts about sarin.
Available at http://www.bt.cdc.gov/agent/sarin/basics/facts.asp. Accessed
December 22, 2004.
3. Centers for Disease Control and Prevention (CDC). Sarin: NIOSH emergency
response card. Available at http://www.bt.cdc.gov/agent/sarin/erc107-44-8.asp.
Accessed December 22, 2004.
4. Cieslak TJ, Rowe JR, Kortepeter MC, et al. A field-expedient approach to theclinical management of chemical and biological casualties. Mil Med.
2000;165(9):659-662.
5. Ben Abrahim R, Rudick V, Weinbroum AA. Practical guidelines for acute careof victims of bioterrorism: conventional injuries and concomitant nerve agent
intoxication. Anesthesiology. 2002;97:989-1004.
6. Briggs SM, Brinsfield, KH, eds. Chemical agents. In: Advanced Disaster Medical
Response. Boston, MA: Harvard Medical International Trauma and Disaster
Institute; 2003:59-70.
7. Jamal GA. Neurological syndromes of organophosphorus compounds. Adverse
Drug React Toxicol Rev. 1997;16:133-170.
8. Himuro K, Murayama S, Nishiyama K, et al. Distal sensory axonopathy aftersarin intoxication. Neurology. 1998;51:1195-1197.

SUGGESTED READING
1. Agency for Toxic Substances and Disease Registry. FAQs for nerve agents (GA,GB, GD, VX). Available at http://www.atsdr.cdc.gov/tfacts166.html. Accessed
January 31, 2005.
2. Agency for Toxic Substances and Disease Registry. Medical management guidelines for nerve agents: tabun (GA); sarin (GB); soman (GD); and VX. Available
at http://www.atsdr.cdc.gov/MHMI/mmg166.html. Accessed January 31, 2005.
3. Arnold JL. CBRNE – nerve agents, G series: tabun, sarin, soman. eMedicine
Journal. Available at http://www.emedicine.com/emerg/topic898.htm. Accessed
January 31, 2005.
4. Henretig FM, Cieslak, TJ, Madsen JM, Eitzen EM, Fleisher GR. The emergency
department response to incidents of biological and chemical terrorism. In:
Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 4th ed.
Philadelphia, PA: Lippincott Williams and Wilkins; 2000:1763-1784.
5. Leikin JB, Thomas RG, Walter FG, Klein R, Meislin HW. A review of nerve
agent exposure for the critical care physician. Crit Care Med. 2002:30:2346-2354.
6. Platoff GE, Baskin SI, Madsen JM. Military Personnel Part III—Chemical
Threats. In: Greenberg MI, Hamilton RJ, Phillips SD, McCluskey GJ, eds.
Occupational, Industrial, and Environmental Toxicology. 2nd ed. Philadelphia, PA:
Mosby; 2003:258-273.
7. Sidell FR. Nerve agents. In: Sidell FR, Takafuji ET, and Franz DR, eds.
Textbook of Military Medicine. Part 1: Medical Aspects of Chemical and Biological
Warfare. Washington, DC: Office of the Surgeon General and Borden Institute;
1997:129-179.

14

EVALUATION FORMTERRORISM AND DISASTER: WHAT CLINICIANS NEED TO KNOW
Sarin
Participant Information
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Practice setting: ❏ Hospital/In-patient ❏ Outpatient/Clinic ❏ Other

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Instructions for Physicians Receiving Credit
The questions that follow may be used to obtain continuing medical education credit. To obtain 1 hour of Category 1 credit towards
the AMA Physician’s Recognition Award, read this case study, which will take one hour of your time, circle the correct answer to each of
the CME questions, complete the evaluation form, and return both the CME question page and the evaluation form via mail or fax to:
Rush University Medical Center
Office of Continuing Medical Education
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Case Study Evaluation
Please rate this case study according to the following scale: 1=Very Poor 2=Poor 3=Fair 4=Good 5=Very Good 6=Excellent
1. Accredited CME activities must be “free of commercial bias for or against any product.” In this regard,
how would you rate this activity? If you perceived any bias, please provide specific comments below.

1 2 3 4 5 6oooooo__________________________________________________________________________

oooooo2. How well did the case study satisfy your purpose for reading it?

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3. To what extent were the stated objectives of the case study achieved?

oooooo4. In general, was the case study well organized and presented?
5. To what extent has this CME activity improved your preparedness to recognize and care for victims of aterrorism attack or other public health disaster?
6. What was your overall rating of this case study?

oooooooooooo7. I would recommend this case study to a colleague.

o Yes

8. Based upon your review of this case, what specific action(s) could you take to enhance disaster
preparedness in your workplace?

Please estimate the probability
that you will act on this item
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C. ___________o Please check this box if you prefer not to be contacted for follow-up about the impact of this activity on your clinical practice.

15

QUESTIONS FOR CONTINUINGMEDICAL EDUCATION
1. What is the pathophysiology of sarin poisoning?
a. Sarin quickly binds to acetylcholinesterase (AChE), leading to an excess ofacetylcholine (ACh) at receptors.
b. Sarin exposure leads to paralysis because of decreased stimulation of muscles byacetylcholine (ACh).
c. Sarin competes with acetylcholine (ACh) for binding to muscarinic receptors.
d. Sarin causes increased release of acetylcholine (ACh) from the axons of neurons.
2. Which of the following best describes a patient exposed to sarin?
a. “Blind as a bat, dry as a bone, hot as a hare, red as a beet, and mad as a hatter”
b. Paranoid, hypertensive, sweating, mydriatic (dilated pupils), and hyperpyrexicc. Weak, twitching, miotic (pinpoint pupils), tearing, salivating, sweating,vomiting, diarrhetic, and seizing
d. Miotic (pinpoint pupils), comatose, hypotensive, hypothermic, hyporeflexive,
seizing, and with decreased bowel sounds
3. How would victims exposed by inhalation of sarin differ clinically from those
exposed solely to liquid sarin?
a. Miosis is never seen after exposure to liquid sarin.
b. With high doses, sudden collapse may be the first clinical effect after either kindof exposure but with liquid exposure would occur after several minutes rather
than immediately.
c. Twitching is not commonly seen after exposure only to sarin vapor.
d. Unlike liquid-exposed patients, victims from sarin vapor may exhibit a gradualonset of symptoms even after removal from exposure.
4. In a hospital setting, what is the role of decontamination for sarin victims?
a. No decontamination is needed by the time victims reach the hospital.
b. Late decontamination is performed solely to protect hospital personnel andfacilities.
c. Decontamination of sarin requires hypochlorite solutions (bleach).
d. Removal of clothing may eliminate most but not all sarin in an exposed victim.
5. Which statement most accurately describes the action of a nerve agent antidote?
a. Diazepam acts as a competitive inhibitor of acetylcholine at muscarinic
receptors.
b. Atropine acts as a little “crowbar” to “pry” the nerve agent away from boundenzyme.
c. Because 2-PAM chloride acts primarily at nicotinic receptors, its main clinicaleffects are on smooth muscle.
d. Atropine acts as the “Pepto-Bismol®” of nerve-agent antidotes by “coating”
muscarinic receptors.

16

errorism
Tand isaster
D
Rush University Medical Center
faculty, in collaboration with facultyfrom the Uniformed Services
University of the Health Sciences(USUHS) authored a case series
to provide continuing medical
education (CME) for terrorism
preparedness and other publichealth emergencies.
A series of 14 case studies was developed to provide innovative learning
opportunities for health professionals
to problem-solve issues related toterrorism or other public healthemergencies. Due to the complicated and volatile nature of a terrorist
event, the case studies were designed
to expand outside the clinicianpatient interaction and involve:• deploying outside resources• notifying appropriate officials• coordinating a response team• dealing with media andconcerned public• initiating emergency/disaster plans
Each case provides the CME user
with decision-making challenges
within his or her discipline, alongwith scenarios that address broader
interdisciplinary issues. This interdisciplinary approach is particularly
important in disaster preparedness,when health professionals will likely
be called on to work outside their
day-to-day experiences.

WHAT
CLINICIANS
NEED TO
KNOW

Authored by experts in the field,
each self-paced case includes athorough case history, questions totest your knowledge, a resource listof additional readings and relevant
websites. One-hour CME andCEU credit is available for eachcase, following the successful completion of the CME questions
included with each case. The CME
and CEU credit is available free ofcharge through March 2007.

INTERDISCIPLINARY
The interdisciplinary cases address
basic medical management,general
disaster planning, communicatingwith the media and concerned
public, and psychosocial casemanagement.
• Inhalational Anthrax• Pulmonary Toxicants• SARS• Smallpox• Viral Encephalitis

The cases in the series include:
MEDICINE
The medicine cases address recognitionof the agent, diagnosis, treatment, andmedical case management.
• Pneumonic Plague• Radiation Attack• Sarin• Smallpox• Staphylococcal Enterotoxin B• Viral Hemorrhagic Fevers
PSYCHIATRY
The psychiatry cases address issuesof disaster psychiatry.
• Emergency Mental Health
After a Suicide Bombing• Psychiatric Sequelae in a
Survivor of 9/11
• Psychosocial Managementof a Radiation Attack

For more information or to order
your free copy of any of the casesin this series, please contact:
Office of Continuing
Medical Education
Rush University Medical Center
Suite 433 AAF
Chicago, Illinois 60612
Telephone: (312) 942-7119
Facsimile: (312) 942-2000
E-mail: cme_info@rush.edu