Download In This Issue - Society of Emergency Medicine Physician Assistants

Volume 24 • Number 2
In This Issue
Lesson 3
Lesson 4
Toxins as Weapons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 2
The LLSA Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 12
Rabies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 13
The Drug Box . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 19
The Critical Image . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 21
CME Questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 22
The Critical ECG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 24
Contributors
2009
October
Ira B. Wood, MD, Michelle M. McLean, MD, and Robert Satonik, MD, FACEP, wrote “Toxins as
Weapons.” Dr. Wood is a clinical instructor and senior resident at Synergy Medical Education Alliance,
Michigan State University College of Human Medicine, Department of Emergency Medicine, in Saginaw,
Michigan. Dr. McLean is medical director of LifeNet Michigan and on the clinical faculty at Synergy Medical
Education Alliance, Michigan State University College of Human Medicine, Department of Emergency
Medicine. Dr. Satonik is associate residency program director at Synergy Medical Education Alliance,
Michigan State University College of Human Medicine, Department of Emergency Medicine.
J. Stephen Bohan, MS, MD, FACEP, reviewed “Toxins as Weapons.” Dr. Bohan is clinical director of
the Department of Emergency Medicine at Brigham and Women’s Hospital and an instructor in Medicine
(Emergency Medicine) at Harvard Medical School in Boston, Massachusetts.
Caroline E. Eady, MD, and Edward J. Otten, MD, wrote “Rabies.” Dr. Eady is chief resident at
the University of Cincinnati Department of Emergency Medicine. Dr. Otten is a professor of emergency
medicine and pediatrics and director of the Division of Toxicology at the University of Cincinnati College of
Medicine in Cincinnati, Ohio.
Daniel A. Handel, MD, MPH, reviewed “Rabies.” Dr. Handel is director of clinical operations in the
Department of Emergency Medicine at Oregon Health & Science University, Portland, Oregon.
Frank LoVecchio, DO, MPH, FACEP, reviewed the questions for these lessons. Dr. LoVecchio is
research director at the Maricopa Medical Center Emergency Medicine Program and medical director of the
Banner Poison Control Center, Phoenix, Arizona, and a professor at Midwestern University/Arizona College
of Osteopathic Medicine in Glendale, Arizona.
Louis G. Graff IV, MD, FACEP, is Editor-in-Chief of Critical Decisions. Dr. Graff is professor of
traumatology and emergency medicine at the University of Connecticut School of Medicine in Farmington,
Connecticut.
Contributor Disclosures
In accordance with ACCME Standards and ACEP policy, contributors to Critical Decisions in Emergency Medicine must
disclose the existence of significant financial interests in or relationships with manufacturers of commercial products that
might have a direct interest in the subject matter. Authors and editors of these Critical Decisions lessons reported no such
interests or relationships.
Method of Participation
This educational activity consists of two lessons with a posttest and should take approximately 5 hours to complete.
To complete this educational activity as designed, the participant should, in order, review the learning objectives, read the
lessons, and complete the online posttest. Release date May 1, 2009. Expiration date April 30, 2012.
Accreditation Statement
The American College of Emergency Physicians (ACEP) is accredited by the Accreditation Council for Continuing
Medical Education (ACCME) to provide continuing medical education for physicians. ACEP designates this educational
activity for a maximum of 5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with
the extent of their participation in the activity. Approved by ACEP for 5 Category I credits. Approved by the American
Osteopathic Association for 5 hours of AOA Category 2-B credit (requires passing grade of 70% or better).
Target Audience
This educational activity has been developed for emergency physicians.
Critical Decisions in Emergency Medicine
Toxins as Weapons
Lesson 3
Ira B. Wood, MD, Michelle M. McLean, MD, and Robert Satonik, MD, FACEP
n Objectives
On completion of this lesson, you
should be able to:
1. Explain the importance of hospitalbased decontamination in both large
and small toxic exposures.
2. Describe the components of the
standard cyanide antidote kit and
their roles in the treatment of a
patient with cyanide toxicity.
3. Discuss the presentation of a patient
suffering from a vesicant exposure.
4. Explain the utility of an unremarkable
chest radiograph in a patient
exposed to phosgene.
5. Prescribe the appropriate antidotal
and supportive therapies based on
the suspected toxin.
6. Recommend the appropriate
treatment plan based on elements of
the history of the exposure.
7. Discuss the similarities and
differences between toxic weapons
and more commonly encountered
toxins.
n From the EM Model
17.0 Toxicologic Disorders
2
17.1 Drugs and Chemical Classes
Fortunately, chemical warfare is
not common. However, the resulting
lack of familiarity with these agents
and their appropriate treatments
makes their rapid identification and
mitigation difficult should the need
arise. When time to treatment has a
significant effect on morbidity and
mortality, proven generalizations and
pattern recognition become tools of
extreme importance.
An emerging term, weaponizable
toxins, represents a paradigm shift
in the way emergency physicians
approach the study of and preparation
for toxin-mediated multiple casualty
events. Traditionally, toxins have
been classified as biological or
chemical. Although this distinction
makes sense from the standpoint of
weapons research, development, and
production, it is of little or no use to
the front-line emergency physician,
who must make rapid decisions with
limited information. Toxin exposures
are all addressed through the same
basic principles of limiting contact
time, recognizing the toxidrome,
and developing a treatment plan that
involves antidotes, if available, and
supportive care.
The term biologic weapon
encompasses both biologic toxins
such as ricin and infectious agents
such as anthrax. The approach to
infectious agent exposures addresses
issues such as patient isolation,
rapid agent identification, and the
development of an appropriate
antibiotic treatment regimen. Through
the practical approach of emergency
medicine, it is easy to see that the
treatment of a patient exposed to ricin
is much more similar to the approach
taken for a patient exposed to sarin
gas than it is to that of a patient
exposed to an infective agent such
as anthrax. By reviewing biologic
toxins together with chemical toxins
and separating them from infectious
agents, we develop a paradigm that is
based on the standardized approach
that must be taken in the emergency
management of toxin exposures.
The terrorist attacks witnessed
at the turn of this century had been
previously unimaginable. It is also
important to realize that emergency
physicians could encounter similar
toxins on a much smaller scale
through accidental poisonings, law
enforcement activities, or industrial
accidents. The physician’s general
approach and treatment priorities
are the same for a patient exposed
to pepper spray administered by law
enforcement officials as they are for
a patient exposed to a nerve agent
released by terrorists.
Case Presentations
n Case One
A male college student was at a
university football game when a riot
broke out. He believes he was sprayed
with pepper spray. The entire event
occurred about 1 hour ago. He comes
through triage with complaints of
burning to his skin and his eyes.
Multiple staff members are also
beginning to complain of burning in
October 2009 • Volume 24 • Number 2
Critical Decisions
• When is decontamination appropriate for a patient
exposed to pepper spray?
• Which treatment should be initiated prior to establishing
intravenous access in a patient who is unresponsive
following a chemical exposure?
• What special concerns about methemoglobinemia in
children should influence treatment in a potential cyanide
exposure?
their eyes. He denies any difficulty in
breathing.
n Case Two
A patient is brought in from a
structure fire. The patient has suffered
no burns. He was talking at the scene,
complaining of headache, weakness,
and dizziness, when he collapsed.
EMS noted that the patient was
not cyanotic but was significantly
hypoxic, with a pulse oximetry of
56%. The paramedics have intubated
the patient and are ventilating him
with a bag valve mask. They have not
established intravenous access.
n Case Three
It is a slow Saturday afternoon in
the department when the emergency
physician receives notification from
dispatch that there has been an
explosion at a political rally at the
downtown convention center. Almost
immediately, the physician is called
into the resuscitation bay to treat a
patient from this explosion who was
brought in by bystanders. The patient
is a young man lying unresponsive
on the stretcher. There are absolutely
no indications of trauma. The
patient seems to have copious airway
secretions; his pupils are constricted,
and his breathing is labored.
Chemical Agents
Incapacitating Agents
Incapacitating agents such as
pepper spray represent some of the
weaponized toxins that emergency
physicians are likely to encounter.
Various formulations of these agents
are available for both law enforcement
use and personal protection. In most
• What is the utility of a normal chest radiograph in a
patient who presents with phosgene exposure?
• What is the acute treatment of seizures associated
with nerve agents? Is it different from the treatment of
epileptic seizures?
• What elements of the history and physical examination
can help determine the likely class of toxin responsible in
a patient who collapses and becomes unresponsive after
a chemical exposure?
cases, these agents are safe, and
their adverse effects are short-lived.
In rare instances there have been
reports of long-term sequelae and
fatalities associated with the use of
these devices.1 The most commonly
used agents are CS (named after its
discoverers Ben Carson and Roger
Staughton) and oleoresin capsicum
(OC spray). They are generally
dispersed as liquids or fine powders.
They have also been used in hand
grenades and cluster bombs.1
Symptoms from incapacitating
agents begin within seconds.
The cutaneous effects of CS are
generally limited to a burning
irritation, but there are reports of
patients developing erythema and
blistering.1 The patient will also
experience intense lacrimation and
an involuntary shutting of the eyes,
known as blepharospasm. Respiratory
symptoms include rhinorrhea, nasal
irritation, shortness of breath, and
coughing. OC, or pepper spray, is
derived from plants of the genus
Capsicum. The key ingredient in
OC is capsaicin. Capsaicin causes
the release of the neurotransmitter
substance P from the peripheral
afferent sensory fibers. This causes
a neurogenic inflammation that is
characterized by vasodilation and a
sensation of pain. The effects of OC
are similar to those of CS. OC tends
to have a quicker onset, involves some
loss of motor control, and can cause a
temporary blindness. Laryngospasm
and respiratory arrest have been
reported.1
The management of exposures
to these incapacitating toxins is not
agent specific. Decontamination is
the important immediate step for all
of them. Patients should be moved
to a well-ventilated area, ideally with
forced air blowing over them. The
patient’s clothing should be removed,
and the skin washed with soap and
copious amounts of water. CS has
a half-life of 15 minutes in water at
room temperature.2 If there are ocular
symptoms, the patient’s eyes may be
flushed using standard techniques.
Some experts favor the use of
evaporative techniques such as fans or
a cold hairdryer over ocular flushing.1
Contact lenses should be removed as
soon as possible, and soft contacts
must be discarded. Significant
cutaneous erythema or dermatitis
can be treated with topical steroids.
Persistent respiratory symptoms could
benefit from inhaled 2-agonists.
Pepper spray exposures occur
frequently enough that they are often
not treated with the aggressiveness
that is seen in the response to other
toxic exposures. Although there is
reasonable variability in the potency
of different preparations, all of these
incapacitating agents have relatively
short half-lives.
CRITICAL DECISION
When is decontamination
appropriate for a patient exposed to
pepper spray?
Although full decontamination
might not be appropriate in every
scenario, it should be a consideration
for every patient exposed to CS or
OC. If a patient is still experiencing
significant symptoms of exposure
after 30 minutes, continued
3
Critical Decisions in Emergency Medicine
exposure should be considered, and
the patient could require a more
formal decontamination. If patients,
visitors, and health care workers
near the patient begin complaining
of symptoms consistent with toxin
exposure, decontamination should be
performed or repeated.
Asphyxiating Agents
Cyanide. Cyanide is the most
deadly weaponizable toxin that the
average emergency physician is likely
to encounter. It is used in many
industries,3 and it is also a product
of the combustion of many modern
materials. It has been reported that
as many as 35% of fire victims have
suffered from toxic exposures to
cyanide.3 The intentional use of
cyanide as a poison or weapon is rare
by comparison.
Cyanide works as a cellular
asphyxiant by inhibiting cytochrome
oxidase and preventing aerobic
metabolism within the mitochondria.
This forces an unsustainable shift
to anaerobic metabolism, which
is responsible for the classic
presentation of an acyanotic patient
who appears hypoxic.4 Significant
exposures often lead to death well
before medical care can be delivered.
Patients who are still alive after a
significant exposure have a brief
window of opportunity during which
medical personnel can provide
effective treatment.
The key to diagnosing cyanide
toxicity often is the history and
setting of events. Cyanide should
be a consideration in any healthy
patient who suddenly collapses in an
environment where cyanide exposure
is possible. Due to its volatility
and rapid dispersion, cyanide gas
is generally only effective if it is
released in a closed, poorly ventilated
environment. It is less likely to be
the cause of a sudden collapse in an
outdoor setting.
Mild cyanide toxicity will present
in a manner similar to anxiety attacks.
Patients may be hyperventilating and
complaining of shortness of breath.
Other symptoms include headaches,
weakness, and dizziness. Because
of their dependence on oxygen,
the central nervous system and the
cardiovascular system are generally
the first to manifest symptoms of an
exposure.
The standard cyanide antidote kit
in the United States contains amyl
nitrite, sodium nitrite, and sodium
thiosulfate (Table 1). The nitrites
are used to convert hemoglobin
to methemoglobin, which has a
stronger affinity for cyanide and
facilitates the removal of cyanide
from the mitochondria. The sodium
thiosulfate acts as a sulfhydryl donor
for rhodanese. Rhodanese is the
enzyme responsible for converting
cyanide to thiocyanate, a much less
toxic metabolite that is then renally
excreted. Thus the treatments are
complementary.
CRITICAL DECISION
Which treatment should be
initiated prior to establishing
intravenous access in a patient who
is unresponsive following a chemical
exposure?
Amyl nitrite from a standard
antidote kit should be administered. It
is packaged in glass pearls. In patients
requiring assisted ventilations, the
amyl nitrite can be delivered via bag
valve mask by placing a crushed pearl
over the oxygen intake valve. When
this method is used, the amyl nitrite
should be used for only 30 seconds
of every minute. Replace the pearl
every 3 minutes.5 Alternatively, the
pearls may be crushed into a gauze
sponge and held under the patient’s
nose.6 Theoretically, this can induce
a methemoglobinemia of 3% to 5%,5
but this may not be reliable in clinical
Table 1.
Summary of cyanide antidotal therapies
a
4
Therapy
Amyl nitritea
Adult Dosing
Crushed into gauze and
inhaled by patient
Pediatric Dosing
Crushed into gauze and
inhaled by patient
Sodium nitritea
300 mg IV push over 2 to 4
minutes
10 mg/kg, or 6 mg/kg
Sodium thiosulfatea
50 mL of 25% solution
Hydroxocobalamin
5 gm over 15 minutes
1.65 mL/kg of 25% solution
over 10 minutes
70 mg/kg
Components of the traditional cyanide antidote kit used in the United States
Notes
Induces 3% to 5%
methemoglobinemia, but not
reliable. Provides potential
for rapid therapy prior to
obtaining intravenous access
Consider sequelae of
methemoglobinemia in
anemic children
Now available as a cyanide
antidote in the United States.
Other forms are too dilute for
this therapy
October 2009 • Volume 24 • Number 2
practice. Amyl nitrite is a bridging
therapy that can be instituted
rapidly. Once venous access has
been established, other, more reliable
therapies should be instituted.
Sodium nitrite is more effective
than amyl nitrite and may raise
methemoglobin levels to over 20%.7
Sodium nitrite is given as 300 mg (10
mL of a 3% solution) intravenously
over 2 to 4 minutes.
CRITICAL DECISION
What special concerns about
methemoglobinemia in children
should influence treatment in a
potential cyanide exposure?
In children, there is significant
concern about the potential decreased
oxygen-carrying capacity associated
with methemoglobin. Assuming a
child has a normal hemoglobin level,
the recommended dose of sodium
nitrite is 10 mg/kg. Since time is of
the essence, it may be unreasonable
to wait for a hemoglobin level before
initiating treatment in a child
presenting with cyanide toxicity. In
those instances, it may be prudent to
administer sodium nitrite in a dose
of 6 mg/kg, as this dose would be
safe, even in a child with a significant
anemia.5
These traditional nitrite therapies
have several drawbacks. If given
too aggressively, they can cause
significant hypotension and
tachycardia. Additionally, the benefits
of methemoglobin come at the price
of an overall decreased oxygencarrying capacity. This is especially
concerning in patients with additional
impairments of tissue oxygenation
such as carbon monoxide poisoning.
For this reason, some experts
recommend avoiding nitrite therapy
in victims of smoke inhalation,
although this is debateable.5
Sodium thiosulfate works
synergistically with the nitrites to
rid the body of its toxic cyanide
load. Rapid administration can cause
hypotension, but otherwise this is a
fairly safe therapy, with rare reports of
hypersensitivity. Sodium thiosulfate
works with the patient’s intrinsic
enzymes to detoxify cyanide. The
metabolite is renally excreted. This
can cause toxicity in patients with
significant renal failure. In severe
circumstances, the medication could
be given and then dialyzed.5 The adult
dose of sodium thiosulfate is 12.5
grams (50 mL of a 25% solution). In
children, the dosage is 1.65
mL/kg of the 25% solution, given over
10 minutes.
Hydroxocobalamin is a therapy
that has been used for decades in
Europe and is now available in the US
market (Table 1). Hydroxocobalamin
combines with cyanide to form
cyanocobalamin, or vitamin B12. This
therapy is generally used in place
of the nitrite therapy, and is also
synergistic with sodium thiosulfate.
Hydroxocobalamin does not hinder
the blood’s oxygen-carrying capacity,
making it an especially attractive
option for smoke inhalation victims.
The adult dosage is 5 grams over 15
minutes. This dose will bind up to
250 grams of cyanide. The pediatric
dose is 70 mg/kg. Hydroxocobalamin
is also used for the treatment of
pernicious anemia. It is important
to realize that the drug preparation
used for pernicious anemia is diluted
to such an extent that it has no
utility as an antidote for cyanide
toxicity. It is also important to note
that sodium thiosulfate will bind
to hydroxocobalamin, so the two
medications should be given through
different veins, if possible.5
During an exposure event, it is
likely that the emergency physician’s
choice of antidote will be dictated
by what is readily available. The best
antidote is generally the one that is
on hand. Obviously, supportive care
that focuses on enhancing tissue
oxygenation through blood pressure
maintenance and supplemental
oxygen therapy is of paramount
importance.
Phosgene. Phosgene is
representative of the asphyxiating
agents that work through direct
effects on the pulmonary tissues, as
opposed to the cellular asphyxiants
like cyanide. Phosgene, or
carbonic dichloride, is a synthetic
chemical commonly used in the
pharmaceutical, pesticide, plastics,
and dye industries. Phosgene can also
be created through the heating of
Freon gas. It is heavier than air and
said to have an odor similar to that of
freshly cut corn or hay. Phosgene was
considered the most lethal chemical
warfare agent in World War I.4
The classic presentation of
phosgene exposure involves some
initial mild irritation of the nasal and
pulmonary passages. This is then
followed by a symptom-free period of
2 to 10 hours before the onset of more
significant pulmonary symptoms.6
CRITICAL DECISION
What is the utility of a normal
chest radiograph in a patient who
presents with phosgene exposure?
It is common for chest radiographs
to appear unremarkable for the first
several hours following an exposure
to phosgene. In fact, dyspnea, or
radiographic evidence of pulmonary
edema within 4 hours of exposure is
associated with a significant exposure
and probably warrants admitting
the patient to an ICU setting.8
Conversely, patients are unlikely to
develop significant lung injury if
they are asymptomatic and have a
clear chest radiograph 8 hours after
exposure.8 An unpredictable minority
of patients can develop significant
symptoms after 48 hours, leading to
the recommendation that exposed
individuals be observed for 48 hours
postexposure.7
Care of the patient exposed to
phosgene or the other primary lung
toxins is primarily supportive. There
are no specific antidotes. Bed rest
is important because postexposure
exertion appears to be related to
a worsening of the inflammatory
response.8 Bronchodilators are
effective, but corticosteroid therapy
remains controversial. Diuretics
should be avoided because they
will exacerbate the hypovolemia
5
Critical Decisions in Emergency Medicine
associated with this noncardiogenic
pulmonary edema.6 Superimposed
infection can be a major contributor
to morbidity and mortality, but
prophylactic antibiotic therapy is
not recommended.8 The mainstay of
therapy is volume replacement and
ventilatory support.6
Nerve Agents
Nerve agents were fist synthesized
as insecticides by German scientists
in 1937. They were stockpiled as
potential weapons by Germany
during World War II but were
not used in war until the IranIraq conflict of the 1980s.9 These
agents are relatively simple and
inexpensive to synthesize, making
them potentially attractive weapons
for terrorists.7 There are five primary
nerve agents that are used as chemical
weapons. They are identified by
a common name and a two-letter
North Atlantic Treaty Organization
(NATO) designation (Table 2). Most
nerve agents are very volatile and
will vaporize at room temperature.
The agent VX is the exception
to this; it requires a temperature
above 38ºC (100.4°F) to cause a
significant vapor hazard.10 All nerve
agents are cholinesterase inhibitors;
therefore, the clinical presentation
of a nerve agent exposure can be
similar to other, more common
cholinergic crises. When compared
with organophosphate insecticide
exposures, nerve agent exposures
generally have a much quicker onset
and a shorter overall duration of effect
and require a lower total dose of
atropine.8
The diagnosis of nerve agent
intoxication is based entirely on
clinical presentation and exposure
history. A scenario in which several
people in close proximity to one
another develop both respiratory and
central nervous system abnormalities
is highly suggestive of nerve agent
exposure.10 Blood cholinesterase
activity studies are not useful in the
acute management of these patients.5
6
The route of exposure significantly
influences the clinical presentation.
Inhalation exposures present rapidly
and with classic signs and symptoms.
Dermal exposures, however, might
not cause symptoms for up to 18
hours.9 Isolated dermal exposures can
present with localized diaphoresis
and fasciculations. Miosis can be
absent or significantly delayed in
patients with pure dermal exposures.
Patients with pure vapor exposures
who do not develop symptoms early
are very unlikely to have a significant
exposure.9
The treatment of a patient with
a significant nerve agent exposure
has three primary components:
supportive care, respiratory support,
and seizure control. Supportive care is
based on the specifics of the exposure
and the patient’s presentation along
with an appreciation for the possible
pathways of deterioration. Specific
concerns center on respiratory
support and the prevention and
treatment of seizures. Atropine is
given as a competitive inhibitor of
the muscarinic receptors to lessen
the respiratory effects of cholinergic
stimulation. Oximes are chemical
compounds that if given early enough
are able to disrupt the chemical bond
between the nerve agent and the
acetylcholinesterase (AChE) active
site, thus allowing reactivation of the
enzyme.
Atropine is not indicated for
patients presenting with miosis
as their only symptom. For
adults, atropine should be given
intravenously at a dose of 2 mg every
2 to 5 minutes until the patient is
breathing easier, or, for intubated
patients, until the patient becomes
less difficult to ventilate. In the
unconscious adult, a higher initial
dose of 6 mg should be given. For
children, the dose should be 0.05 to
0.1 mg/kg up to 4 mg given every 5
to 10 minutes. It is important to note
that the more familiar symptomatic
bradycardia dose of 0.02 mg/kg is
not a sufficient treatment for children
with nerve agent intoxication.10
Pralidoxime chloride (2-PAM) is
the only oxime approved for nerve
agent treatment in the United States.
If given early enough, it is able to
remove the nerve agent from the
AChE, and form a complex with the
nerve agent that is then excreted in
the urine. If pralidoxime is given too
rapidly, significant hypertension can
occur. It should be given to adults at
1 to 2 gm IV drip over 30 minutes;
it may then be given as a continuous
drip at 500 mg/hour. For children,
the dose is 15 to 25 mg/kg as a slow
IV push or IM injection, up to 600
mg.
The effectiveness of 2-PAM is time
dependent. Nerve agents undergo
a process known as aging, during
which they essentially develop a
covalent bond with the AChE. Once
this bond is formed, 2-PAM is unable
to remove the nerve agent from the
Table 2.
Common nerve agents
Common Name
Soman
NATO Designation
GD
Sarin
GB
Tabun
Cyclosarin
VX
GA
GF
VX
Characteristics
Ages in 2 to 6 minutes,2 camphor-like
odor3
50% aged in 5 hours,4 odorless; most
volatile
Fruity odor3
50% aged at 38 hours,5 clear amber
color; oily; least volatile; most
persistent
October 2009 • Volume 24 • Number 2
AChE. Aging occurs at different rates
for different nerve agents (Table 2).
Soman has the shortest aging time (a
few minutes), while VX has very little
aging effect.7
Aging is not a contraindication
to the use of oxime therapy. If AChE
is not reactivated by oxime therapy,
it will need to be replaced through
de novo synthesis. This process can
take several weeks.5 Although aging
can reduce the effectiveness of oxime
therapy, any AChE regeneration will
be beneficial to the patient.
Seizures can occur in the face of
a significant nerve agent exposure.
Seizures are thought to be related
to the cholinergic hyperstimulation.
Patients with significant nerve
agent exposures can also present
with flaccid paralysis. Patients with
paralysis should have continuous EEG
monitoring to detect the presence of
nonconvulsive seizures.
CRITICAL DECISION
What is the acute treatment of
seizures associated with nerve
agents? Is it different from the
treatment of epileptic seizures?
High-dose atropine might
terminate seizure activity if given
within the first 5 minutes of the
seizure. After 5 minutes the seizure
will begin causing biochemical
changes within the brain that will
make anticholinergic therapy alone
ineffective, and benzodiazepines
must be employed. Midazolam
appears to be slightly more effective
and is the benzodiazepine of choice
for these seizures, but others are
acceptable. Diazepam is available in
10-mg auto-injectors. When choosing
between midazolam, lorazepam,
and diazepam, the drug of choice in
this scenario is the drug on hand.
Pentobarbital may be used if the
seizure is refractory but can cause
significant respiratory depression.
Fosphenytoin does not have a role in
the treatment of nerve agent-related
seizures.5
Ocular complaints are a significant
component of the presentation when
patients are exposed to nerve agents.
Miosis was present in 99% of the
patients with moderate or worse
exposures when sarin was released
into the Tokyo subway system.5
Note that miosis is not as reliable an
indicator of exposure in children.10
In addition to the constricted
pupils, there is also ciliary muscle
contraction that causes pain. Patients
may get some relief from these ocular
manifestations with tropicamide
drops, 1 to 2 drops of a 0.5% solution.
Prepackaged auto-injectors
containing atropine and 2-PAM are
available for military and prehospital
use. The kit used in the United
States is the Mark 1 nerve agent
auto-injector kit. The Mark 1 kits are
also part of the Centers for Disease
Control and Prevention (CDC)
CHEMPACK project, which aims to
rapidly deploy stockpiled resources
Table 3.
Pediatric use of auto-injector therapies for nerve agent exposures
Weight
Atropine
< 20 kg
20 to 40 kg
> 40 kg
2-PAM
> 12 kg
Diazepam
> 30 kg
Therapy
0.5-mg pediatric auto-injector
1-mg pediatric auto-injector
2-mg adult auto-injector
600-mg adult auto-injector
10-mg adult auto-injector
to the areas of need in the event of a
mass casualty event.5 The kit contains
a 2-mg atropine auto-injector, and a
600-mg pralidoxime auto-injector.
For medication administered via
intramuscular injection, the autoinjectors have been shown to be
more effective than traditional
intramuscular injection methods.5
In the military arena, soldiers are
instructed to administer three Mark
1 kits, delivering a total of 6 mg of
atropine and 1,800 mg of 2-PAM. If
symptoms persist, they administer
only the atropine syringe from
additional kits.5 Diazepam autoinjectors are also available in 10-mg
doses.
Pediatric auto-injectors are also
available for the administration of
atropine (Table 3). They come in
0.5-mg and 1-mg doses. Children in
the 20- to 40-kg weight range should
receive the 1-mg dose; children who
weigh less than 20 kg should get a
0.5-mg dose, and children weighing
more than 40 kg can receive the
2-mg adult dose.5 Although ageand weight-appropriate dosing is
always ideal, it is not always possible
in mass casualty scenarios with
taxed resources. Some authors have
suggested that in children with
symptomatic nerve agent intoxication,
the toxic effect of over-medication
with atropine or 2-PAM would present
fewer sequelae than failure to treat the
nerve agent intoxication.10
Vesicants
Mustard agents are clear, odorless,
oily substances that vaporize easily.
Although there are several types of
“mustard agents,” sulphur mustard is
the agent generally used as a weapon.
This agent was used in World War I
and was referred to as the “king of the
battle gases.”11 More recently, sulphur
mustard gas appears to have been
used by Iraq, during its conflict with
Iran in the late 20th century. The
exact toxic mechanisms of sulphur
mustard are not clear, but it appears
to undergo an alkylation reaction
with cellular components, including
7
Critical Decisions in Emergency Medicine
DNA and RNA. Research into these
mechanisms has found several
nitrogen mustards that are used in the
treatment of cancers.12
Sulphur mustard is generally
found as a transparent brown liquid,
with an odor similar to that of garlic.
The color and odor are the result
of impurities in the manufacturing
process. In vapor form, it will
rapidly pass through clothing to the
underlying skin. It has also been
shown to penetrate wood and leather
barriers.11 The vapor has much better
skin penetration than the liquid.
Up to 80% of liquid mustard will
evaporate from the skin, leaving
only 20% of the agent available for
penetration.12
Sulphur mustard exposure has a
delayed presentation when compared
to most chemical weapons. Ocular
symptoms such as lacrimation,
a foreign body sensation, and
conjunctivitis develop 4 to 12 hours
postexposure and are some of the
earliest clinical manifestations of
mild exposures.12 In severe exposures
edema, blepharospasm, and transient
blindness can appear within 3 hours
of exposure.12 There is an inverse
relationship between the severity of
the exposure and the delay in clinical
presentation.
Skin manifestations will begin
with redness and pruritus in 4 to
8 hours. The classic blisters and
Nikolsky sign are generally not
apparent for at least 2 days. Skin
lesions can be treated like seconddegree burns, with the understanding
that they will often take much longer
to heal than thermal burns. The fluid
requirements are the same as for
burn patients—with an important
exception. The fluid loss in a sulphur
mustard exposure does not occur
until blister formation; therefore
aggressive fluid therapy begins with
blister formation and not over the first
24 hours as in thermal burns.12
Pulmonary manifestations
following mustard gas exposure can
be rapidly fatal. An early presentation
clinically similar to bronchitis
8
should be considered a sign of
direct pulmonary injury. In patients
with stridor and hoarseness, early
tracheostomy should be considered.
Laryngospasm is a persistent threat.
Sulphur mustard exposure is also
associated with the formation of
pseudomembranes, similar to those
seen in diphtheria, which can cause
fatal obstructions.12
Systemic effects can cause a
profound immunosuppression with
leukopenia. This usually peaks on
days 7 to 9.12 Significant long-term
effects tend to involve the pulmonary
system. The most common long-term
pulmonary manifestation is a chronic
bronchitis.12
Decontamination only limits
patient exposure if performed within
the first few minutes. Water should
be used in copious amounts. Military
forces have specific decontamination
formulations. In a civilian setting,
there may be some benefit to the
use of talcum powder or flour for
decontamination.12
Treatment for sulphur mustard
exposures is primarily supportive.
Cutaneous lesions should be
treated like second-degree burns.
Respiratory support and anticipation
of deterioration are important aspects
of the treatment plan.
Biologic Toxins
Botulinum Toxin
Botulinum toxin is one of the
most toxic substances known and
is relatively simple to produce. One
gram of pure toxin, if effectively
dispersed as an aerosol, could kill
up to 1 million people.4 Inhalation
exposure does not occur in nature,
and case reports of accidental
industrial exposures are limited. Food
contamination is also a potential
source of exposure.
The classic, acute presentation
of botulinum intoxication involves
bilateral cranial nerve palsies and
descending motor paralysis. Initially,
a bulbar paralysis is seen, followed
by the loss of head control and a
descending skeletal muscle paralysis.
Ingestion symptoms generally develop
within 12 to 72 hours, but there are
reports of delays of up to 1 week.4
Although the data are limited, it is
thought that inhalation exposures
would follow a similar time course.
There is no change in mentation,
and there should not be a fever.
Blood, cerebrospinal fluid, and
imaging study results are generally
unremarkable.4 Intoxication may
be confused with Guillian-Barré
syndrome, myasthenia gravis, and
stroke.4
Treatment is based on supportive
therapy and the administration of
antitoxin. Antitoxin will not reverse
preexisting paralysis, but it will
halt further progression. A trivalent
antitoxin, covering serotypes A, B,
and E is available in the United States
through the CDC and state health
agencies. An experimental heptavalent
antitoxin is available to the US
military. The antitoxin has a half-life
of several days and is administered in
a single, one-vial dose. The currently
approved antitoxin is equine derived,
and therefore, a small test dose is
advised prior to administering the full
dose to allow for the identification and
pretreatment of allergic individuals.
Ricin
Ricin is a toxin derived from the
bean of the plant Ricinus communis
(castor bean). It binds to the 28S
ribosomal subunit, interfering with
protein synthesis. Annually, there
are 1 million tons of castor beans
processed into castor oil worldwide.4
The waste mash from this process is
5% ricin by weight.4 The industrial
extraction process leaves no
active ricin in the oil.13 The beans
themselves are generally only toxic
if they are macerated or chewed to
release the toxin, although death
has been reported with as few as 2
beans.13 Unfortunately, there are no
specific treatments for ricin toxicity,
and supportive care is the only
currently available option.13
Ricin has been used as a criminal
toxin in recent history. Ricin has been
October 2009 • Volume 24 • Number 2
found in the mailroom of a US senator
and in a letter to the White House.
Although it was never proved, ricin is
the likely agent that killed Bulgarian
defector Georgi Markov in September
of 1978 when it was injected into him
as a small pellet from the modified tip
of a common umbrella.
Ingestion of ricin leads to necrosis
of the gastrointestinal epithelium.
There is associated hepatic, splenic,
and renal necrosis.4 This progresses to
significant fluid losses, bleeding, and
shock. Death often occurs after the
second day. The initial presentation is
nonspecific, with colicky abdominal
pain, vomiting, and diarrhea.
Laboratory abnormalities can reflect
renal and hepatic involvement.
Symptom onset is generally within 4
to 6 hours, but can be as long as 10
hours.13
Injection exposures will present
with local tissue damage as well as
necrosis of local and regional lymph
nodes.4 This can then progress to
involvement of the gastrointestinal
tract, liver, and kidneys. Disseminated
intravascular coagulation and
third-degree heart block could
also develop.14 Onset of symptoms
can take up to 12 hours after an
exposure.13
There is poor information on
inhalational exposure of ricin in
humans. Limited case reports show
fever, arthralgias, chest tightness, and
respiratory symptoms.13 Eventually
there can be pulmonary necrosis
and the development of pulmonary
edema.14 Symptom onset can be
delayed up to 24 hours.
Response to Toxic Disasters
Analyses of mass casualty
incidents reveal that the same
mistakes tend to be repeated time
and time again.15 Hospital personnel
tend to believe that their role in a
mass casualty chemical exposure
will be to treat multiple victims
of a known exposure.15 It is also
commonly believed that most of the
victims will be brought to the hospital
by the local EMS system and will
have been decontaminated prior to
their arrival.15 History clearly shows
otherwise.
The 1995 release of sarin in the
Tokyo subway system provides
important insight.16 At the closest
hospital, only 7% of the victims
arrived by ambulance; 59% of the
patients either walked or arrived
by taxi.16 Three victims suffered
prehospital cardiac arrest. Two of
the three were taken by private
vehicles to hospitals that were farther
away.16 There was a 20% secondary
contamination rate among nurses
and physicians.16 The toxin was not
identified for several hours, and once
it was identified, the information was
not disseminated effectively to the
local hospitals. Within the hospital,
the correct diagnosis was made based
on clinical presentation and specialist
consultation via telephone.16
It is clear that this sort of incident
might not be recognized before
patients have arrived at an emergency
department. As a result, there is
a risk of contamination within
the emergency department before
a mass exposure event has even
been recognized by the health care
system. It is imperative that disaster
planning include a contingency plan
to deal with facility and personnel
contamination.
Decontamination is of paramount
importance any time a chemical
exposure is expected. The decision
to decontaminate should be made
by frontline personnel and not
postponed for physician evaluation.
It is always better to err on the
side of decontamination than to
unnecessarily expose personnel
to potentially deadly toxins.
Decontamination should occur with
tepid water. Warm water can cause
vasodilation that could enhance the
dermal absorption of toxins.7
Empiric Treatments
Empiric treatment in the face of
significant toxin exposures will save
lives. This requires that emergency
physicians make important treatment
decisions rapidly with limited
information. This type of medical
decision making is the foundation of
emergency medicine as a specialty.
CRITICAL DECISION
What elements of the history
and physical examination can
help determine the likely class of
toxin responsible in a patient who
collapses and becomes unresponsive
after a chemical exposure?
Nerve agents and cyanide
toxicity require immediate unrelated
treatments and have similar
clinical presentations in significant
exposures. Cyanide toxicity would be
more likely in an industrial setting
and generally requires an enclosed,
poorly ventilated environment to
induce a rapid and dramatic onset;
its rapid dispersal limits its effect in
well-ventilated areas. Nerve agents
are more likely to present as part of
a criminal release, with the intent
to harm several persons. These
agents can be effective even when
widely dispersed over open areas.
An isolated nerve agent exposure is
possible, however, especially during
the manufacture and preparation of
the agent.
Nerve agents present with
classic cholinergic symptomology.
This involves miosis, diaphoresis,
salivation, lacrimation, fasciculations,
and bronchorrhea. In severe cases
there can be a flaccid paralysis.
Cyanide is a cellular asphyxiant. It
causes a nonpulmonary hypoxia.
Cyanide is not associated with the
secretions or fasciculations seen in
nerve agent exposures.8 Patients
exposed to cyanide will have a high
anion-gap acidosis and above normal
venous oxygen saturation.
Case Resolutions
n Case One
This patient was moved to a
well-ventilated area. His clothing
was removed, and his skin was
washed with soap and water.
Some erythema was seen on his
arms, which had been exposed.
9
Critical Decisions in Emergency Medicine
Hydrocortisone cream was applied
following decontamination. The
patient’s contact lenses were removed
and discarded. Morgan lenses were
placed, and his eyes were flushed
with room-temperature saline.
Fluorescein stain was applied to each
eye, and a slit-lamp examination
revealed no corneal abrasions. He was
monitored for 45 minutes, and his
symptoms completely resolved. He
was discharged, with hydrocortisone
cream for his skin eruption.
n Case Two
Because this patient collapsed
after being rescued from a fire that
occurred in a clothing factory with
wool and silk products, cyanide
poisoning was suspected. A cyanide
antidote kit was obtained, and an
amyl nitrite glass pearl was crushed
and placed over the oxygen intake
valve of the bag valve mask. It was
used for 30 seconds of every minute,
and a new pearl was placed every 3
minutes. Intravenous access was then
obtained, and sodium nitrite was
administered at 300 mg over about
3 minutes. The patient was placed
on a cardiac monitor and monitored
for hypotension and tachycardia.
The patient had no known history of
renal failure, and a 12.5-gram dose of
sodium thiosulfate was administered.
The patient’s laboratory values were
monitored, and the methemoglobin
level was 15%. He was admitted to the
ICU.
n Case Three
This presentation and history
of events was suspicious for an
intentional toxin release, specifically,
Pearls and Pitfalls
• Children can be less tolerant of the methemoglobinemia associated with nitrite
therapy for cyanide toxicity than adults, especially if they are anemic. If a child’s
hemoglobin level is unknown, a dose of 6 mg/kg of sodium nitrite may be
given. Nitrite therapy may also be withheld. Hydroxocobalamin therapy is not
associated with these concerns.
• Patients who have abnormal chest radiographs or experience respiratory
distress within 4 hours of a phosgene exposure are likely to have
significant deterioration and warrant admission to an ICU.
• Although the aging of a nerve toxin can limit the
effectiveness of an antidote, antidote treatment is still likely
to benefit the patient and should not be withheld.
• Children exposed to a nerve agent are less likely
to develop miosis than are adults.
• Because there are rare case reports of patients developing significant
pulmonary edema up to 48 hours after their exposure to phosgene gas,
some experts recommend a 48-hour observation period for these patients.
• Inhalation exposures take effect rapidly, but the effects of
dermal exposures can be delayed up to 8 hours.
• Most victims of toxic disasters do not arrive by ambulance; hospital disaster
plans should address the possibility that there will be a delay in recognizing
the event and that the emergency department could become contaminated.
• A patient who collapses and becomes unresponsive after a chemical exposure
has likely been exposed to either a nerve agent or cyanide. Patients exposed
to nerve agents present with miosis, diaphoresis, salivation, lacrimation,
fasciculations, bronchorrhea, or even flaccid paralysis; patients exposed to
cyanide will present with none of the classic cholinergic symptomology.
10
the release of a nerve agent. The
emergency physician realized that the
emergency department had become
a “hot zone,” and that he and the
staff were now potential victims. The
institutional response protocol was
initiated. Emergency department staff
quickly assembled a rapid-response
decontamination team and began
decontamination of the patient and
exposed staff. The hospital was
notified that this exposure was an
intentional release of a vaporized
nerve agent. Minimal crosscontamination of staff was expected.
The patient and contaminated staff
were treated with atropine and
2-PAM.
The hospital initiated the mass
casualty plan and took measures
to increase surge capacity.
Unfortunately, this plan had not
addressed the possibility that the
emergency department would become
contaminated and be forced to close.
Additional staff members were called
in. Because it was a Saturday and
there were no scheduled surgeries,
the emergency physician was able to
move patients from the observation
unit to the preoperative holding area,
where they could still be appropriately
monitored. This enabled conversion of
the observation unit into a temporary
emergency department.
In the end, the toxic agent was
poorly dispersed, and the hospital
received only a handful of patients.
However, this scenario revealed
several flaws in the hospital’s
response plan. The most important
problem was the lack of a contingency
plan that addressed contamination
and closure of the emergency
department.
Summary
Toxic weapons exposures are
uncommon events; however, when
presented with the victim of a
possible toxic weapon, emergency
physicians must act quickly and
decisively. Decisions made within the
first few minutes of patient contact
can have a significant effect on the
October 2009 • Volume 24 • Number 2
outcome for the patient, as well as the
community. Successful management
will depend on recognition of a
potential exposure and identification
of the likely toxicant. Timely toxin
identification is likely to rely on
the clinical acumen and resource
utilization of the emergency
physician. Prehospital and public
safety personnel may not recognize
the threat before transporting patients
to the emergency department; the first
suspicion of a toxin exposure might
not arise until after the first patients
have arrived in the emergency
department. It is imperative that
response plans to toxic exposures
do not rely entirely on advance
notification from prehospital
resources.
References
1. Smith J, Greaves I. The use of chemical incapacitant
sprays: a review. J Trauma. 2002;52(3):595-600.
2. Blain PG. Tear gases and irritant incapacitants.
1-chloroacetophenone, 2-chlorobenzylidene
malononitrile and dibenz[b,f]-1,4-oxazepine. Toxicol
Rev. 2003;22(2):103-110.
3. DesLauriers CA, Burda AM, Wahl M.
Hydroxocobalamin as a cyanide antidote. Am J Ther.
2006;13(2):161-165.
4. Greenfield RA, Brown BR, Hutchins JB, et
al. Microbiological, biological, and chemical
weapons of warfare and terrorism. Am J Med Sci.
2002;323(6):326-340.
5. Lawrence DT, Kirk MA. Chemical terrorism attacks:
update on antidotes. Emerg Med Clin North Am.
2007;25(2):567-595.
6. Muskat PC. Mass casualty chemical exposure and
implications for respiratory failure. Respir Care.
2008;53(1):58-63; discussion 63-66.
7. Fry DE. Chemical threats. Surg Clin North Am.
2006;86(3):637-647.
8. Kales SN, Christiani DC. Acute chemical emergencies.
N Engl J Med. 2004;350(8):800-808.
9. Lee EC. Clinical manifestations of sarin nerve gas
exposure. JAMA. 2003;290(5):659-662.
10. Baker MD. Antidotes for nerve agent poisoning:
should we differentiate children from adults? Curr
Opin Pediatr. 2007;19(2):211-215.
11. Rice P. Sulphur mustard injuries of the skin.
Pathophysiology and management. Toxicol Rev.
2003;22(2):111-118.
12. Kehe K, Szinicz L. Medical aspects of sulphur mustard
poisoning. Toxicology. 2005;214(3):198-209. Epub
2005.
13. Audi J, Belson M, Patel M, et al. Ricin poisoning: a
comprehensive review. JAMA.
2005;294(18):2342-2351.
14. Madsen JM. Toxins as weapons of mass destruction.
A comparison and contrast with biological-warfare
and chemical-warfare agents. Clin Lab Med.
2001;21(3):593-605.
15. Kirk MA, Deaton ML. Bringing order out of chaos:
effective strategies for medical response to mass
chemical exposure. Emerg Med Clin North Am.
2007;25(2):527-548.
16. Tokuda Y, Kikuchi M, Takahashi O, Stein GH.
Prehospital management of sarin nerve gas terrorism
in urban settings: 10 years of progress after the Tokyo
subway sarin attack. Resuscitation.
2006;68(2):193-202.
11
Critical Decisions in Emergency Medicine
The LLSA Literature Review
“The LLSA Literature Review” summarizes articles from ABEM’s “2010 Lifelong Learning and Self-Assessment Reading List.”
Many of these articles are available online in the ACEP LLSA Resource Center (www.acep.org/llsa) and on the ABEM web site.
Disclosing Harmful Medical
Errors to Patients
Reviewed by Pooja Agrawal, MD, and J. Stephen Bohan, MD,
MS, FACEP; Harvard Affiliated Emergency Medicine Residency;
Brigham & Women’s Hospital
Gallagher TH, Studdert D, Levinson W. Disclosing harmful medical
errors to patients. N Engl J Med. 2007;356:2713-2719.
Medical errors are common. Even with ongoing and appropriate efforts to decrease the incidence of medical errors,
some amount of error is unavoidable. Patients are increasingly expecting to be informed if a medical error occurs. Physicians should be trained in and become comfortable with
discussing harmful medical errors with their patients.
There are several models for addressing disclosure of medical errors. The most obvious is that the responsible clinician
has the necessary conversation with the patient involved. In
order for this to be effective, clinicians need to get basic instruction on how to handle these situations; simulation can
be used as an educational tool. Another model involves risk
managers or medical directors who would coach the physician when disclosure is warranted. In another model, the
involved clinician is moved to the periphery and a “rapid
response team” conducts the necessary disclosure. There is,
however, concern as to how this last method might affect the
patient-physician relationship.
Many physicians have not been trained to have this kind
of conversation with patients and are not comfortable doing
so. This has been a barrier to open disclosure. Another significant barrier is the physician’s fear of litigation if an error
is revealed. Will an apology or disclosure be considered a
legal admission of responsibility for an error? What effect will
disclosure have on patient satisfaction? These questions are
as yet unanswered.
The Joint Commission issued its first nationwide disclosure standard in 2001 and further clarified the standard in
2006. These standards strongly recommend that patients
be informed about all care outcomes, including potentially
harmful or unanticipated ones. They link compliance with
this standard to hospital accreditation. As a result, 69% of
hospitals evaluated in 2005 had established disclosure policies.
Many states do not consider disclosure of a medical error as an admission of guilt. Several government and private
12
legal initiatives promote disclosure of medical errors and
de-emphasize legal liability; however the effect of disclosure
on litigation is still largely unknown. Prominent disclosure
programs that have been operating for some time report a
significant reduction in the cost and frequency of litigation
after their programs began; however, these findings have not
been rigorously assessed or validated.
The widespread implementation of disclosure policies is
inevitable. There are nuances of this topic that must be better
understood, including the best method for disclosing error
and the associated medical and legal implications. In the future, it is likely that full and open disclosure of medical errors
to patients will become standard practice.
Highlights
• Medical errors are inevitable and must be addressed
appropriately.
• There are several models for disclosure of medical errors; in
all cases, appropriate physician education is necessary.
• The legal implications of disclosing a medical error are not
defined; however, initial data suggest that admitting to an
error does not increase rates of litigation.
October 2009 • Volume 24 • Number 2
Rabies
Lesson 4
Caroline E. Eady, MD, and Edward J. Otten, MD, FACMT, FAWM
n Objectives
On completion of this lesson, you
should be able to:
1. Discuss routes of rabies transmission.
2. Describe the importance of early
postexposure prophylaxis.
3. Describe the process for definitively
identifying rabies infection.
4. Detail appropriate treatment
regimens following rabies exposure.
5. Identify symptoms of rabies infection.
n From the EM Model
10.0 Systemic Infectious Disorders
10.6 Viral
Although rabies is not a common
disease in the United States, it is still
among the leading infectious killers
worldwide, claiming 40,000 to 70,000
lives each year.1,2 This disease affects a
disproportionate number of children,
who are too young to understand the
dangers of wild animals and do not
report exposures to their parents.3,4
Rabies is a single-stranded RNA
virus of the Lyssavirus genus.1,5 It
is carried by wild animals and is
transmitted to humans through
exposure to infected saliva, most
often from a bite.1,2 It is a fatal virus,
so early identification of an exposure
is important to allow for neutralizing
immunoglobulin and vaccine
administration.6
An estimated 40,000 people will
present with a request for a rabies
vaccine in the United States this year.3
There is a fixed supply of vaccine
available, so practitioners must be
able to determine who is truly at
risk so that they can ration supplies
accordingly. Beginning in June 2007,
the Sanofi Pasteur plant, maker of
the IMOVAX rabies vaccine, has been
undergoing renovations to comply
with FDA requirements for such
facilities. Because of this, production
has been drastically reduced, and
Novartis, who produces the RabAvert
vaccine, has not been able to meet the
current demand, which has increased
from previous years. The renovations
for the Sanofi Pasteur plant are
scheduled to be finished by the end
of 2009.7
Emergency physicians must also
be aware of the need to take detailed
histories from persons presenting
with vague viral symptoms, especially
those who have recently traveled,
because missing a case of rabies will
prove fatal for the affected patient.
Case Presentations
n Case One
A 22-year-old man presents to
the emergency department after
being bitten by a dog while he was
out jogging. He states that the dog
came out of a yard and grabbed his
right lower leg and when he pulled
away the dog jumped up and bit his
right thigh. The dog was a mixed
breed with a collar on, and it ran
away afterwards toward the same
yard. He did not pursue the dog but
knows the address where the attack
occurred. His past medical history
is positive for asthma, for which he
uses an inhaler as needed. He has no
known allergies, and his last tetanus
update was 3 years ago. He has two
4-cm abrasions to his right posterior
calf and a 1-cm puncture wound to
his right lateral thigh that is bleeding
slightly. Distal motor, sensory, and
vascular functions are intact. The
wounds are washed with soap and
water and irrigated with povidoneiodine solution.
n Case Two
A 12-month-old girl is brought
to the emergency department by
the girl’s mother because she found
a bat in her daughter’s room, and
13
Critical Decisions in Emergency Medicine
the pediatrician thought the child
should be evaluated. The child has
been healthy with normal milestones;
she is on no medications and has
had no prior hospitalizations. She
has been acting normally, has had
no change in her mental status, and
has had no fever, rash, or illness.
Her immunizations are current. She
does have a few bruises from falling
while playing. The bat was found
on the floor under the girl’s bed.
The mother brought the dead bat
with her in a plastic container. The
child’s examination shows a healthy,
alert, playful child with a few typical
knee abrasions/contusions and some
superficial scratches on her face and
neck. The child is able to walk, and
her strength and balance are normal
for her age.
n Case Three
A 42-year-old game warden for the
state was bitten by a stray dog that he
had been securing in a rural region
of the state. The dog was quarantined
and later euthanized because of
erratic behavior; its remains were
sent to the state pathologist for
analysis. The patient has had rabies
preexposure prophylaxis, but it has
been more than 10 years, and his last
antibody test was 5 years ago. He has
a bite to his right lower leg over his
shin that is 2 cm by 4 cm and a 1-cm
puncture wound to the medial aspect
of his calf. His past medical history
is significant for previous animal
bites and a forearm fracture 5 years
ago. His motor, sensory, and vascular
examinations are normal distal to the
wound.
CRITICAL DECISION
Which animals are known to carry
the rabies virus?
Any carnivorous mammal can
be a carrier of rabies. In the United
States, most domestic animals are
required to be vaccinated against the
disease, so it is rare for a dog or cat to
spread infection8,9; however, there is
no way to measure compliance with
these requirements. Cats typically
have a higher incidence of rabies,
14
likely because there are more stray
cats than stray dogs, and cats tend to
be more nocturnal, which increases
their risk for exposure to bats.3 In
2003, there were 321 reported cases
of rabies in cats in the United States
and only 117 reported cases in dogs.3
Since 1966, there have been only
two documented cases of rabies
transmissions from dogs to humans
in this country.3 For those traveling
in foreign countries, dogs are still
the main source of infection.1 In this
country, bats are the largest reservoir
for the disease, accounting for almost
90% of infections acquired within
the borders.1,9,10 Other wild animals
known to harbor the disease in the
United States are foxes, raccoons,
and skunks. Small rodents can be
infected by the disease if they are
bitten by a rabid animal, but most
die immediately from the inflicted
wounds or are eaten. Transmission
from a rodent to a human has never
been documented.1 Rabies can also
be passed from human to human in
rare instances. Almost all of these
cases involve transplanted organs.11,12
However, there are case reports of
transmission through saliva involving
human bites and extensive kissing.1
CRITICAL DECISION
Who should receive preexposure
prophylaxis?
Anyone who has a high likelihood
of being directly exposed to the
virus should receive prophylaxis.
Anyone working in a laboratory
handling the rabies virus should be
vaccinated before work is begun. The
largest group affected in the United
States is veterinarians, especially
those working in remote areas
with more likely exposure to wild
animals. Those who work in animal
control, fish and game workers, and
spelunkers should also receive the
vaccine. For the average American,
rabies preexposure prophylaxis is
only recommended for those traveling
to and living for more than 1 month
in an area where rabies is known to
be endemic.3
Preexposure prophylaxis involves
vaccination with 1 mL of cell culture
vaccine on days 0, 7, and 28.1,3 The
frequency of boosters is based on
the actual risk of potential exposure.
Those working with the virus should
have titers drawn every 6 months.
Those working in areas where rabies
is known to be endemic should have
levels drawn every 2 years. Those
veterinarians and animal workers
who choose to get the vaccine do not
need to have titers monitored on a
regular basis even if there is a known
risk of rabies in their area, because
there is no significant risk for rabies
transmission.3 If these individuals
do have a potential exposure, their
titers can be drawn to determine need
for treatment with further doses of
the vaccine. If there is a significantly
high risk of exposure, postexposure
prophylaxis should be initiated until
titer levels are available.
There are no known
contraindications to preexposure
prophylaxis. There have been
numerous safety studies involving
both the human diploid cell vaccine
(HDCV) and the purified chick
embryo cell vaccine (PCECV).
There have been no reported deaths
following administration of either
vaccine. Pain around the injection
site is the most common side effect.
Mild systemic reactions, including
headache and gastrointestinal
symptoms, were seen in 10% to
50% of patients receiving the HDCV
and in 0 to 30% of those receiving
the PCECV. With repeat doses of
HDCV, less than 0.001% of patients
experienced systemic hypersensitivity
reactions.3
CRITICAL DECISIONS
Who should receive postexposure
prophylaxis?
The primary route of rabies
transmission is from a direct bite.
It could also be spread if saliva,
cerebrospinal fluid, or brain matter
comes in contact with broken skin,
and it can pass through mucous
membranes.1,13 There have been
October 2009 • Volume 24 • Number 2
multiple cases where rabies has
been transmitted through organ
transplants.11,12 There are also a few
case reports that indicate aerosol
transmission; however, all these cases
have involved a large concentration
of the virus, either in caves that are
infested with bats or in a laboratory
setting.1,13
Postexposure prophylaxis should
be offered to anyone with a suspected
exposure to rabies, especially anyone
who was potentially exposed to a
bat. Approximately 1% of bats have
the rabies virus, and it is difficult
to determine whether a person has
been bitten by a bat.1 Bats teeth are so
small and sharp that bats can bite a
person without being noticed and the
bite might not leave any identifiable
mark behind. Everyone who suspects
they have been bitten by a bat, those
who find a dead bat in their room,
and those who have camped outside
in areas where bats are known to
have rabies should receive immediate
prophylaxis. All spelunkers who enter
caves where bats are present should
receive prophylaxis if they were not
vaccinated prior to the potential
exposure.1,3
Patients who have been bitten by
wild carnivorous animals should
also begin immediate postexposure
prophylaxis. If the animal was caught,
it should be shipped to an approved
laboratory for testing. If the animal is
found to be free of rabies, the patient
may stop the vaccination schedule.3,8
Diagnosing rabies is done under
immunofluorescent examination of
the cerebral tissue.
Patients bitten by healthy
appearing domestic animals may
delay rabies postexposure prophylaxis
if the animal is quarantined. These
animals should be observed for 10
days, and if they show no sign of
infection during the observation
period they may be released, and
the patient does not need to be
vaccinated.1,3 If the animal shows any
signs of infection, the patient should
start the vaccination schedule and
continue until the animal has been
tested at an approved facility. Signs
of infection in an animal include
excessive salivation, aggression,
paralysis, daytime activity in
nocturnal animals, and impaired
movement.
As stated before, rodents have
not been shown to pass the rabies
virus to humans. Humans who have
been bitten by chipmunks, beavers,
woodchucks, etc., need not receive
postexposure prophylaxis, although
it is frequently given to allay fears of
rabies.
To avoid person-to-person
transmission via organ
transplantation, no organs should
be obtained from a person who
died of an unexplained neurologic
disease.1,3,11,12 If organs are procured
from such a patient, immediate
testing for the rabies virus should
be performed. If anyone who
has received an organ transplant
presents with neurologic sequelae,
rabies should be tested for, other
potentially affected recipients should
be notified, and the organ recipient
should immediately be started on
postexposure prophylaxis until the
diagnosis is disproved.
There are no known
contraindications for postexposure
prophylaxis. Rabies is uniformly fatal;
anyone with a potential exposure
should begin immediate prophylactic
treatment. As with the preexposure
prophylaxis, patients can experience
localized pain at the injection site,
and a few will also experience mild
systemic symptoms. There have
been no serious side effects reported
from administration of human rabies
immunoglobulin (HRIG).1,3
CRITICAL DECISION
What is the schedule for rabies
immunoglobulin and vaccine
following a potential exposure?
The primary mode for preventing
infection remains local wound care.1
Anyone presenting with an obvious
bite should have it thoroughly
irrigated. Although povidone-iodine
cleansing solutions have the potential
to further damage tissue, they have
been shown to be effective in killing
the virus and should be used for bite
wounds.3 As with any bite wound,
the physician should allow it to heal
by secondary intention, and sutures
should not be used. The physician
should consider approximating the
wound if there is significant bleeding
or significant exposure of underlying
tissue or if the wound is located in a
cosmetically significant area such as
the face or hand.14
The most important feature of
postexposure prophylaxis remains
the immunoglobulin. This provides
immunity to the virus while the body
mounts its own response, triggered
by the vaccine. Those who received
preexposure prophylaxis need not
receive the immunoglobulin, despite
titer levels.2,3 Within the United
States, the immunoglobulin is
made from the serum of previously
vaccinated humans. The dose is 20
units/kg.1-3,6,10 The immunoglobulin
should be injected directly into the
wound site. If the amount is too
large to be injected into the affected
area, the remainder should be given
intramuscularly, usually in the deltoid
muscle. For persons affected by
multiple bites, the immunoglobulin
may be diluted so that each bite
site can be injected. Because of the
expense and difficulty that is involved
in producing HRIG, many other
countries manufacture an equine
version. This version is as effective as
the human version in most studies
but has a higher incidence of allergic
reactions. The newer, purified form
of equine vaccine has an almost
undetectable rate of serum sickness,
but the less purified version used
in many countries because of cost
issues is associated with a 15% to
40% incidence of serum sickness.
The dose of equine immunoglobulin
is 40 units/kg, and it should be
administered in the same manner as
the human version.3,6 Because of the
current shortage of immunoglobulin,
some hospitals in other countries
do not offer it at all, which is
15
Critical Decisions in Emergency Medicine
why preexposure prophylaxis is
recommended for those traveling to
areas where rabies is known to be
endemic. The immunoglobulin has
been shown to be effective up to 7
days after exposure, so travelers have
time to get the appropriate treatment,
even if it is not readily available in the
community where they were bitten.
There are many forms of rabies
vaccine available worldwide. The
approved versions within the United
States are the HDCV and the PCECV.
Other countries have a wider variety
of vaccines, derived from duck
embryo, vero cells, and nerve tissues
from affected animals. These vaccines
may not be as effective, and patients
returning to this country can require
further treatment if they have not
mounted a significant titer. The dose
for all vaccines should be 1 mL,
Pearls
• All patients potentially exposed
to a bat should be treated
with rabies prophylaxis.
• Patients who have received
preexposure prophylaxis do
not need immunoglobulin
after exposure.
• Thorough wound care is
the first step in preventing
rabies infection.
• Waiting for official laboratory
testing should never delay
prophylactic treatment following
a potential exposure to rabies.
Pitfalls
• Infiltrating immunoglobulin
too close to the vaccine can
deactivate the vaccine.
• Failure to quarantine a domestic
animal could result in prolonged
unnecessary prophylaxis.
• Patients presenting with
clinical signs of rabies have
almost no chance of survival.
16
given intramuscularly, preferably
in the deltoid muscle, on days 0, 3,
7, 14, and 28.1-3,6,10 For those who
had already received preexposure
prophylaxis, vaccine need only be
given as 1 mL, intramuscularly, on
days 0 and 3, despite titer levels.1,3
Immunoglobulin has been shown to
neutralize the vaccine, so different
needles should be used for the
administration of immunoglobulin
and vaccine, and the vaccine should
be given at a remote site to avoid
interaction.3 Because rabies has a
long incubation period, the vaccine
schedule should be started even if
an exposure is identified days to
weeks after the fact.1,3,6 The schedule
should be followed as if the day of
presentation is day 0. If a patient
misses a dose of the vaccine, the
next dose should be given as soon
as possible, and the schedule should
be followed with appropriate time
intervals from the new date.
CRITICAL DECISIONS
How is rabies definitively
diagnosed?
Most cases of rabies are diagnosed
in sacrificed animals. Any wild
animal that was involved in a bite
and any domestic animal that
displays inappropriate behavior,
including aggression, excessive
salivation, paralysis, or impaired
movement, while in quarantine
should be killed and shipped
to an approved laboratory for
testing. These laboratories use an
immunofluorescence technique to
identify rabies antigen on cerebral
tissues.15 This technique requires
intact brain tissue, so care must
be taken to preserve tissues while
shipping the animal. To confirm a
negative diagnosis, a tissue culture
using mouse neuroblastoma cells is
grown, and can be tested within a
day.1,15 Many foreign countries do
not have the laboratory facilities
to undertake expensive diagnostic
studies; however, the affected animal’s
brain might be examined for typical
cytoplasmic inclusion bodies within
the tissue. These inclusions have been
found to have very low sensitivity,
and there have been documented
cases of human rabies after an animal
has been deemed not to have rabies
based on the microscopic examination
of brain tissue.1
Diagnosing rabies in a living
human subject is difficult, especially
in the first few days following
exposure. The most reliable test
available at this time is PCR testing
for rabies RNA in an affected person’s
saliva.1,2,15 Skin biopsies are also
routinely performed when trying to
verify the diagnosis of rabies. The
sample is usually taken from the neck,
as a high concentration of nerve tissue
around the hair follicles increases
the chance of detection. These
samples are then examined using the
immunofluorescence technique to
detect rabies antigen. The presence
of rabies antibody in the serum of
an individual who has received no
previous vaccine or immunoglobulin
is also diagnostic.1,15 Because of the
low sensitivity of these tests, a person
suspected of having rabies should
be tested several times before the
diagnosis is excluded.
CRITICAL DECISION
How do patients with rabies
infection present?
Rabies has a prolonged incubation
period, from a few weeks up to many
years.1,2,5,6,10,13 The incubation period
varies depending on the severity of
the exposure and the proximity of the
bite to the central nervous system.
Rabies spreads via retrograde fast
axonal transport until it reaches the
central nervous system, at which
point it rapidly disseminates. Most
affected patients will have some
symptoms present within the first 3
months following exposure.
Early symptoms of rabies are
usually associated with local reactions
around the entry site. Patients might
experience pain, itching, burning,
or numbness in the affected area.
Patients then develop constitutional
symptoms, including malaise, fever,
October 2009 • Volume 24 • Number 2
cough, and anorexia. Because of the
vague nature of the symptoms, most
patients will be dismissed by health
care workers as having a simple viral
illness if a detailed history is not
obtained.1,4,6,10
There are two defined subsets
of clinical rabies presentations, the
furious or encephalitic form and the
paralytic form. The furious form
is much more common. Patients
affected by the furious form present
with periods of hyperactivity,
agitation, and hallucinations, mixed
with periods of lucidity similar to
delirium. They could experience
spasms, most notably in response to
stimuli. One well-defined symptom
of rabies is hydrophobia—fear of
water. The proposed reason for this
is that patients experience spasms
of the larynx when they attempt to
drink water, and the body mounts
a conditioned response to avoid
the inciting trigger. Some patients
have been documented to have such
strong cases of hydrophobia that
they experience spasms if they only
think of water. The paralytic form of
rabies is clinically indistinguishable
from Guillain-Barré syndrome
in many cases. Patients present
with progressive paralysis that is
irreversible. Both types of rabies
progress to coma and autonomic
instability, ultimately resulting in
death.1,2,10,13 The mechanism of
disease has yet to be described.
Multiple studies have shown that
rabies does not cause neuronal
death, so neuronal dysfunction is the
current theory behind the clinical
manifestation of rabies.5
CRITICAL DECISION
What is the treatment for overt
rabies infection?
Rabies is fatal once a person has
developed clinical symptoms.1,2,4,6,10,13
There is no available treatment, and
only one person who received no
vaccine or immunoglobulin has ever
been known to survive. The survivor
was a 15-year-old girl who was
treated with therapeutic coma and
antivirals. This case was documented
in 2004, and the girl remains alive,
although she suffers from moderate
neurologic sequelae.16 This regimen
has been repeated as an experimental
treatment, but no further patients
have survived. Once a person has
symptoms, and a confirmed diagnosis
is made, there is no proven benefit to
life-saving measures.
Case Resolutions
n Case One
In this case, the patient notified
local animal control officials, who
quarantined the animal. The dog’s
owner was able to show proof that
the animal was currently vaccinated
against rabies. At the end of the
10-day quarantine period, the dog
had exhibited no abnormal behavior
and was allowed to return home.
The patient’s wound healed with
only minimal scarring. Antibiotics
were not judged necessary for this
patient, since they are not indicated
for leg wounds in immunocompetent
patients. He had no long-term
sequelae from the incident.
n Case Two
The child in question received
HRIG and the first two doses of
HDCV. The bat’s body was sent to the
local health department laboratory
for testing and was found to be free of
rabies. The vaccination schedule was
stopped, and the child had no longterm sequelae following the incident.
n Case Three
A radiograph revealed no sign
of fracture or foreign body in the
wound received by the game warden.
The wound was cleansed with soap
and water and irrigated with dilute
povidone-iodine solution. Because the
wound was gaping over the patient’s
shin, it was reapproximated with a
single layer of staples. This patient
had received previous immunization
against the rabies virus, so HRIG was
not indicated. However, because the
animal exhibited erratic behavior, the
patient was given the recommended
two doses of booster vaccine. His
wound healed without incident,
and he experienced no long-term
sequelae from the incident. It was
recommended that he have titers
drawn every 2 years because of the
high-risk nature of his job.
Summary
Emergency physicians should
be aware of the incidence of rabies
in their practice area. All animal
bites should be reported to the local
board of health. Most dogs in the
United States have been vaccinated
against rabies, and dogs with collars
usually belong to someone who
can be identified and notified to
quarantine the animal. Cats are more
at risk for rabies because of the lack
of vaccination and because they are
more often allowed to roam at night
when they might come in contact
with a rabid animal. An attempt
should be made to identify and isolate
an animal that has bitten someone.
Rabies prophylaxis is not indicated
if the animal can be located and
remains healthy during the 10-day
observation period.
Bats are the number one source of
rabies in the United States, accounting
for 90% of the reported cases. A bite
from a bat can go unrecognized,
especially in a small child.
Postexposure prophylaxis should
be initiated, and the bat should be
sent to the local health department
laboratory to be examined for rabies.
Although overt rabies is not a
common presentation to emergency
departments, many people will
present seeking advice and
treatment following an animal bite
or exposure. Emergency physicians
must be aware of the risks for rabies
and take care to treat wounds
appropriately and dispense vaccine
and immunoglobulin in high-risk
cases. Failure to do so may lead to
the development of rabies, which is
uniformly fatal.
References
1. Wilkerson JA. Rabies. In: Auerbach B, ed. Wilderness
Medicine. 5th ed. Philadelphia, PA: Mosby/Elsevier;
2007:1206-1225.
17
Critical Decisions in Emergency Medicine
2. Wyatt J. Rabies—update on a global disease. Pediatr
Infect Dis J. 2007;26:351-352.
3. Manning SE, Rupprecht CD, Fishbein D, et al.
Human rabies prevention—United States, 2008:
recommendations of the Advisory Committee on
Immunization Practices. MMWR Recomm Rep.
2008;57(RR-3):1-28.
4. Warrell MJ. Emerging aspects of rabies infection: with
a special emphasis on children. Current Opin Infect
Dis. 2008;21:251-257.
5. Fu ZF, Jackson AC. Neuronal dysfunction and death in
rabies virus infection. J Neurovirol. 2005;11:101-106.
6. Takayama N. Rabies: a preventable but incurable
disease. J Infect Chemother. 2008;14:8-14.
7. Centers for Disease Control and Prevention.
Temporary unavailability of rabies pre-exposure
vaccination. Online article updated May 20, 2008.
Available at: http://www.cdc.gov/rabies/news/200805-20_PreEVax.html. Accessed March 31, 2009.
8. Lackay SN, Kuantg Y, Fu ZF. Rabies in small animals.
Vet Clin Small Anim. 2008;38:851-861.
9. Belotto A, Leanes LF, Schneider MC, et al. Overview of
rabies in the Americas. Virus Res. 2005;111:5-12.
10. Hankins DG, Rosekrans JA. Overview, prevention, and
treatment of rabies. Mayo Clin Proc. 2004;79:671-676.
11. Bronnert J, Wilde H, Tepsumethanon V, et al. Organ
transplantation and rabies transmission. J Travel Med.
2007;14:177-180.
12. Jackson AC. Rabies. Neurol Clin. 2008;26:717-726.
13. Jackson AC. Rabies: new insights into pathogenesis
and treatment. Curr Opin Neurol. 2006;19:267-270.
14. Maimaris C, Quinton DN. Dog-bite lacerations: a
controlled trial of primary wound closure. Arch Emerg
Med. 1988;5:156-161.
15. Woldehiwet Z. Clinical laboratory advances in
the detection of rabies virus. Clin Chim Acta.
2005;351;49-63.
16. Centers for Disease Control and Prevention. Recovery
of a patient from clinical rabies—Wisconsin 2004.
MMWR Morb Mortal Wkly Rep. 2004;53:1173-1175.
18
October 2009 • Volume 24 • Number 2
The Drug Box
Pralidoxime
By Michael Glueckert, MD; Summa Health System Emergency Medicine Residency
Organophosphate poisoning from pesticides is an uncommon problem in emergency medicine, but these potent
cholinesterase inhibitors can cause severe cholinergic toxicity following cutaneous exposure, inhalation, or ingestion.
They bind to acetylcholinesterase and render this enzyme nonfunctional. This inhibition leads to an overabundance
of acetylcholine in the synapse. The dominant clinical features of acute cholinergic toxicity are bradycardia, miosis,
lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, and diarrhea. Treatment with pralidoxime and
atropine can reverse these symptoms.
Pralidoxime
Mechanism of Action
Indications
Dosing
Side Effects
Estimated Cost
Contraindication/Precautions
Reactivates cholinesterase inactivated by phosphorylation from exposure to
organophosphate pesticides by displacing the enzyme from its receptor sites; removes the
phosphoryl group from the active site of the inactivated enzyme.
Organophosphate poisoning; acetylcholinesterase inhibitor toxicity; nerve agent toxicity
management (unlabeled use)
Organophosphate poisoning – Initial: 30 mg/kg IV over 20 minutes; maintenance: 4-8 mg/kg/
hour IV
Acetylcholinesterase inhibitor toxicity – Initial: 1-2 g IV followed by increments of 250 mg IV
every 5 minutes until response observed
(may be given IM or SQ if IV is not feasible)
Tachycardia, hypertension, dizziness, headache, drowsiness, rash, nausea, muscle rigidity,
weakness, diplopia, hyperventilation, laryngospasm
$400 (based on Summa Health System charges to patient)
Hypersensitivity to pralidoxime; poisonings due to phosphorus, phosphates, or pesticides of
carbamate class (can increase toxicity of carbaryl)
Use with caution in patients with myasthenia gravis and in those with renal impairment
Should not be administered without concurrent atropine, to prevent worsening symptoms
due to transient oxime-induced acetylcholinesterase inhibition
19
Critical Decisions in Emergency Medicine
20
October 2009 • Volume 24 • Number 2
The Critical Image
A 3-year-old girl presenting after an unprovoked attack by a pit bull. On arrival, the patient was awake and
alert with no neurologic deficits, but she had multiple puncture wounds to the scalp. Noncontrast CT was
obtained to assess for intracranial injury.
On soft tissue windows,
fat (in this case,
intraorbital) looks nearly
as black as air
Normal air in ethmoid air cells
Fat appears gray
on bone windows
Pneumocephalus
(black)
Normal air in
mastoid air cells
Pneumocephalus
(black)
Pneumocephalus
(black)
Fracture
}
Fracture
Normal air in
mastoid air cells
This case illustrates several important points:
• Dog bites are forceful injuries capable of penetrating the skull, particularly in young children. Scalp wounds should be
evaluated for intracranial injury.
• CT should be inspected on soft tissue windows to assess for intracranial hemorrhage and on bone windows to assess
for fracture.
• Intracranial air (pneumocephalus) is more visible on bone windows, where it alone appears black. On this window
setting, all other tissues appear gray or white. On soft tissue windows, air appears nearly black but can be difficult to
distinguish from other low-density substances including fat.
The patient was taken to the operating room for repair of injuries and recovered uneventfully.
Feature Editor: Joshua S. Broder, MD, FACEP
21
Critical Decisions in Emergency Medicine
CME Questions
Qualified, paid subscribers to Critical Decisions in Emergency Medicine may receive CME certificates for up to 5
ACEP Category I credits, 5 AMA PRA Category I Credits™, and 5 AOA Category 2-B credits for answering the following
questions. To receive your certificate, go to www.acep.org/criticaldecisionstesting and submit your answers online. You
will immediately receive your score and printable CME certificate. You may submit the answers to these questions at any
time within 3 years of the publication date. You will be given appropriate credit for all tests you complete and submit
within this time. Answers to this month’s questions will be published in next month’s issue.
1. A 46-year-old man presents with shortness of breath. He
is a maintenance worker at a local factory, and earlier in
the day he had tightened a pipe fitting that was leaking
“some sort of gas.” When asked, he states that the odor
of the gas reminded him of a farm. His chest radiograph
looks like that of someone with early adult respiratory
distress syndrome, and he has mild, scattered wheezes.
He requires 100% oxygen via nonrebreathing mask to
maintain adequate oxygen saturation. Which of the
following management strategies is most appropriate?
A. albuterol nebulizer treatments  3, every 20 minutes, 125
mg methylprednisolone, and discharge with a prescription for
prednisone, 20 mg PO three times daily for 4 days
B. albuterol nebulizer treatments  3 every 20 minutes, and
admit to ICU
C. furosemide, 60 mg IV, and admit to ICU
D. intravenous antibiotics, and admit to a telemetry bed on the
medical floor
E. repeat chest radiograph in 4 hours, if normal discharge from
emergency department
2. A 15-year-old boy was exposed to pepper spray about 2
hours ago. The nurse in the examination room is rubbing
her red eyes and coughing. The patient is complaining of
a burning sensation on his face and neck and is unable
to open his eyes. His lung sounds are clear, and he has no
complaints of respiratory difficulty. Which of the following
is an appropriate next step?
A. give him 50 mg of diphenhydramine intramuscularly
B. initiate decontamination
C. neutralize the irritant by applying baking soda to the patient’s
face
D. no treatment is necessary
E. use a bag valve mask and crush an amyl nitrate pearl near the
intake valve
3. Which of the following is true regarding exposure to
sulphur mustard gas?
A. the earliest manifestations are often ocular
B. early administration of a commercially available antidote kit will
prevent further clinical deterioration
C. exposure is identified by the characteristic early onset of
bullous blistering
D. thick canvas clothing will prevent vapor penetration
E. treatment with atropine eliminates all symptoms
22
4. What effect should be anticipated from administration
of botulinum antitoxin in a patient who has ingested
botulinum toxin and is experiencing significant weakness
of his respiratory muscles?
A. the antitoxin should prevent further progression of the disease
B. the antitoxin will prevent the patient from becoming
contagious to others
C. the antitoxin will reverse the paralysis that the patient has
developed
D. no allergies have been reported
E. once patients progress to the point of requiring respiratory
support, the antitoxin is no longer indicated
5. Which of the following is the most appropriate and
effective treatment for a continual seizure that began 15
minutes after a nerve agent exposure?
A. alprazolam orally
B. atropine
C. midazolam intravenously
D. physostigmine
E. pyridoxine
6. Which of the following is an accurate statement regarding
cyanide exposure?
A. flaccid paralysis is often the initial finding
B. it is a cellular asphyxiant
C. miosis is a common presentation
D. pulmonary hypertension is a common cause of death
E. secretions should be treated with atropine
7. Which of the following is the correct method for
administering amyl nitrite pearls in a patient without
intravenous access?
A. administer the amyl nitrate for 30 minutes out of every hour
B. crush the pearl and place it over the intake valve located on the
side of the bag valve mask
C. an intact tablet should be placed over the intake valve located
on the side of the bag valve mask
D. mix the amyl nitrite pearl with water and nebulize the solution
E. vascular access is essential, as amyl nitrate must be given
intravenously
8. Which of the following is accurate regarding pepper
spray?
A. an alkylation reaction occurs binding to DNA and RNA
B. binding to the acetylcholinesterase receptor elicits the effects
C. commonly created by the heating of Freon gas
D. hydroxocobalamin is the appropriate treatment for acute
exposure
E. the neurotransmitter substance P is released from peripheral
afferent sensory fibers
October 2009 • Volume 24 • Number 2
9. A patient presents with a bulbar paralysis and loss of head
control. Which of the following exposures is most likely
the cause?
A. anthrax
B. botulinum toxin
C. cyanide
D. phosgene
E. ricin
10. Which of the following is the most common initial
presentation of ricin intoxication?
A. bronchorrhea
B. cranial nerve palsy
C. hypoxia
D. lacrimation
E. nausea and colicky abdominal pain
11. Which of the following describes the postexposure
prophylaxis dosing schedule for human diploid cell vaccine
(HDCV) for rabies exposure?
A. 1 mL every other day
B. 1 mL on days 0, 3, 7, 14, 28
C. 20 units/kg IV on day 0
D. 20 units/kg on days 0, 3, 7, 14, 28
E. depends on the weight of the patient
12. A 19-year-old man is bitten by a rat while cleaning out his
garage in Ohio. What is his risk for rabies?
A. all wild animals are at high risk for rabies
B. rats are high-risk vectors of rabies; the patient should obtain
rabies immunization
C. rats are unlikely to carry rabies, and immunization is not
indicated
D. rats that are found in the Eastern United States are likely
carriers
E. rodents in general usually do not carry rabies, but rats are the
exception
13. Which of the following statements is true?
A. the HDCV should be infiltrated as near as possible to the
wound site
B. the HDCV should only be given subcutaneously
C. the site for HDCV infiltration should be different from the site
of human rabies immunoglobulin (HRIG) administration
D. the site for HDCV infiltration should be in the same extremity
as HRIG
E. the site of rabies immunization is not important
15. Which of the following animals is most likely to carry
rabies in the United States?
A. cat
B. dog
C. rabbit
D. skunk
E. squirrel
16. Which of the following statements concerning rabies
transmission is true?
A. rabies can be transmitted via respiratory droplets
B. rabies can be transmitted via transplanted organs
C. rabies is commonly transmitted from human to human
D. rabies is never found in cats
E. the rabies source is usually identified in fatal cases
17. The definitive diagnosis of rabies can be made by which of
the following methods?
A. observing a domestic animal for hydrophobia
B. observing a wild animal for 14 days for signs of rabies
C. performing a brain biopsy of any suspected patient and
looking for Negri bodies
D. performing an immunofluorescent antibody test on the
patient’s urine
E. performing PCR testing for rabies RNA on the patient’s saliva
18. Clinical rabies can present as:
A. the encephalitic form in humans
B. the encephalitic/furious form or the paralytic form
C. the paralytic form in adults
D. the paralytic form in children
E. viral gastroenteritis
19. The case fatality rate for clinical rabies is:
A. 10%-20%
B. 20%-50%
C. 50%-75%
D. 99%-100%
E. dependent on comorbid factors
20. Which of the following is correct regarding rabies?
A. it is common in dogs in the United States
B. it is a DNA virus
C. it is rarely vaccinated for in the United States
D. it is transmitted via bites by wild animals primarily
E. it is transmitted via needlestick
14. Which of the following is correct regarding clinical rabies?
A. patients present with variable symptoms and signs
B. patients present with vomiting and diarrhea primarily
C. symptoms develop within 7-10 days of inoculation
D. symptoms develop within 3-4 weeks of inoculation
E. symptoms develop within 30 days of inoculation
Answer key for September 2009, Volume 24, Number 1
1
D
2
A
3
E
4
D
5
D
6
D
7
B
8
B
9
A
10
A
11
E
12
C
13
C
14
D
15
E
16
C
17
C
18
C
19
A
20
A
The American College of Emergency Physicians makes every effort to ensure that contributors to College-sponsored publications are knowledgeable authorities in their fields. Readers are nevertheless advised that the statements
and opinions expressed in this series are provided as guidelines and should not be construed as College policy unless specifically cited as such. The College disclaims any liability or responsibility for the consequences of any
actions taken in reliance on those statements or opinions. The materials contained herein are not intended to establish policy, procedure, or a standard of care.
23
NONPROFIT
U.S. POSTAGE
P A I D
DALLAS, TX
PERMIT NO. 1586
October 2009 • Volume 24 • Number 2
Critical Decisions in Emergency Medicine is the official
CME publication of the American College of Emergency
Physicians. Additional volumes are available to keep
emergency medicine professionals up-to-date on relevant
clinical issues.
Editor-in-Chief
Louis G. Graff IV, MD, FACEP
Professor of Traumatology and Emergency Medicine,
Professor of Clinical Medicine, University of
Connecticut School of Medicine; Farmington,
Connecticut
Section Editor
J. Stephen Bohan, MS, MD, FACEP
Executive Vice Chairman and Clinical Director,
Department of Emergency Medicine, Brigham &
Women’s Hospital; Instructor, Harvard Medical School,
Boston, Massachusetts
Feature Editors
Michael S. Beeson, MD, MBA, FACEP
Program Director, Department of Emergency Medicine, Summa Health System, Akron, Ohio; Professor,
Clinical Emergency Medicine, Northeastern Ohio
Universities College of Medicine, Rootstown, Ohio
The Critical ECG
A 57-year-old man with a history of schizophrenia presenting after an overdose.
Joshua S. Broder, MD, FACEP
Assistant Clinical Professor of Surgery, Associate
Residency Program Director, Division of Emergency
Medicine, Duke University Medical Center, Durham,
North Carolina
Amal Mattu, MD, FACEP
Program Director, Emergency Medicine
Residency Training Program,
Co-Director, Emergency Medicine/Internal Medicine
Combined Residency Training Program, University of
Maryland School of Medicine, Baltimore, Maryland
Associate Editors
Daniel A. Handel, MD, MPH
Director of Clinical Operations, Department of Emergency
Medicine, Oregon Health & Science University, Portland,
Oregon
Frank LoVecchio, DO, MPH, FACEP
Research Director, Maricopa Medical Center Emergency
Medicine Program; Medical Director, Banner Poison
Control Center, Phoenix, Arizona; Professor, Midwestern
University/Arizona College of Osteopathic Medicine,
Glendale, Arizona.
Sharon E. Mace, MD, FACEP
Associate Professor, Department of Emergency
Medicine, Ohio State University School of Medicine;
Faculty, MetroHealth Medical Center/Cleveland Clinic
Foundation Emergency Medicine Residency Program;
Director, Pediatric Education/Quality Improvement
and Observation Unit, Cleveland Clinic Foundation,
Cleveland, Ohio
Robert A. Rosen, MD, FACEP
Medical Director, Culpeper Regional Hospital,
Culpeper, Virginia
George Sternbach, MD, FACEP
Clinical Professor of Surgery
(Emergency Medicine), Stanford University
Medical Center, Stanford, California
Sinus rhythm with sinus arrhythmia, rate 75, prolonged QT. The major abnormality
found in this ECG is the markedly prolonged QT interval (QT interval 0.520 seconds,
QTc interval 0.581 seconds). Prolonged QT interval is associated with hypokalemia,
hypomagnesemia, hypocalcemia, acute myocardial ischemia, elevated intracranial
pressure, drugs with sodium channel blocking effects (for example the cyclic
antidepressants, quinidine, etc.), hypothermia, and congenital prolonged QT
syndrome. In this case, the abnormality was caused by an overdose of one of the
patient’s antipsychotic medications. These medications, as well as many others, are
associated with the prolonged QT interval and the potential for developing torsade de
pointes.
Feature Editor: Amal Mattu, MD, FACEP
From: Mattu A, Brady W. ECGs for the Emergency Physician. London: BMJ Publishing;
2003:102,141. Available at www.acep.org/bookstore. Reprinted with permission.
Editorial Staff
Mary Anne Mitchell, ELS
Managing Editor
Mike Goodwin
Creative Services Manager
Jessica Hamilton
Editorial Assistant
Lilly E. Friend
CME and Subscriptions Coordinator
Marta Foster
Director and Senior Editor
Educational and Professional Publications
Critical Decisions in Emergency Medicine is a trademark
owned and published monthly by the American College
of Emergency Physicians, PO Box 619911, Dallas TX
75261-9911. Send address changes to Critical Decisions
in Emergency Medicine, PO Box 619911, Dallas TX
75261-9911, or to [email protected].
Copyright 2009 © by the American College of Emergency
Physicians. All rights reserved. No part of this publication
may be reproduced, stored, or transmitted in any form
or by any means, electronic or mechanical, including
storage and retrieval systems, without permission in
writing from the Publisher. Printed in the USA.
[email protected]