Volume 32 Number 8 August 2018

Tourist Trap
The ease and speed of travel facilitate exposure to
conditions not endemic to the area where patients
seek treatment. With international travel on the rise,
particularly during summer months, emergency
physicians must be prepared to evaluate and manage
patients who become ill abroad. It is critically important
to build a framework for assessing returned travelers
who present with fever, as such cases can pose serious
threats to patients and public health.

Feeling No Pain
Emergency physicians manage a spectrum of acute
medical and traumatic conditions that often require
painful treatments. In such cases, aptly administered
procedural sedation and analgesia can improve the
experience for both the provider and the patient.
Because the appropriate regimen varies based on the
particulars of each case, clinicians should thoroughly
understand the advantages and potential risks of
sedatives, dissociative agents, and analgesics.

THE OFFICIAL CME PUBLICATION OF THE AMERICAN COLLEGE OF EMERGENCY PHYSICIANS

IN THIS ISSUE
Lesson 15 n Fever in the Returned Traveler . . . . . . . . . . . . . . . . . . . . . . 3
Critical Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Critical Decisions in Emergency Medicine is the official
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 Tourist Trap
Fever in the
Returned Traveler

LESSON 15

By Lauren Page Black, MD, MPH; Andrew Martin, MD;

and Elizabeth DeVos, MD, MPH
Dr. Black is an emergency medicine fellow at the University of Florida,
College of Medicine — Jacksonville. Dr. Martin is an attending physician in
the Department of Emergency Medicine at Emergency Resources Group
in Jacksonville, Florida. Dr. DeVos is an associate professor of emergency
medicine and the medical director of International Emergency Medicine
Education at the University of Florida, College of Medicine — Jacksonville.

Reviewed by David J. Pillow, Jr, MD, FACEP

OBJECTIVES
On completion of this lesson, you should be able to: CRITICAL DECISIONS
1. List the elements of a complete travel history.
n What specific details should be obtained when
2. Identify and manage cases of suspected malaria and inquiring about a patient’s travel history?
viral hemorrhagic fever.
3. Synthesize an assessment based on involved organ n How should suspected malaria be approached,
systems and travel history to identify high-risk and what other diseases should be considered?
conditions in febrile returned travelers.
n What are the potential causes of hemorrhagic
4. Recognize reportable causes of fever in the returned
fever, and how should they be managed?
traveler.
n What diseases should be considered in a febrile
FROM THE EM MODEL returned traveler with abdominal pain, respiratory
1.0 Signs, Symptoms, and Presentations complaints, or neurological symptoms?
1.1 Abnormal Vital Signs
n Which diseases must be reported to the CDC?
1.1.2 Fever

The ease and speed of travel facilitate exposure to conditions not endemic to the area where patients
seek treatment. With international travel on the rise, especially during summer months, emergency physicians
must be prepared to evaluate and manage those who become ill abroad. An estimated 64% of travelers
become ill abroad.1 Fortunately, most of these diseases are mild and self-limiting, evidenced by upper-
respiratory and gastrointestinal symptoms.2

August 2018 n Volume 32 Number 8 3

 CASE PRESENTATIONS
■ CASE ONE
A 35-year-old woman presents
with generalized malaise, fever, chills,
headache, and abdominal pain over the
past week. Initial laboratory tests show
mild anemia and thrombocytopenia
with a normal WBC count. The patient
reveals that she returned from Uganda
in East Africa 14 days ago, where she
was visiting her grandparents. She did
not take any prophylactic medications
during her trip.
However, more serious pathogens,
including malaria, dengue fever, rickettsial
infections, and typhoid fever, are diagnosed
with varying frequencies in returned
travelers with systemic febrile illness.
Travel-related diseases can pose
significant diagnostic challenges for
physicians who do not encounter these
conditions regularly, but preparation and
an organized clinical approach can help
mitigate the risks associated with these
common disorders.
CRITICAL DECISION
What specific details should be
obtained when inquiring about a
patient’s travel history?
A careful travel history should identify,
at minimum, the geographic region visited,
reason for travel, timeline of travel, possible
exposures, pre-travel immunizations, and
chemoprophylaxis.
Travel Destination
Disease risk varies significantly by
region. For example, a febrile patient who
returns from Sub-Saharan Africa may be
more likely to have malaria than someone
who returns from another region, where
dengue fever or other diseases are more
prominent.3 Similarly, rickettsial infections,
yellow fever, enteric fever, and many other
diseases are endemic to certain areas, so
the risk of exposure varies greatly based on
the region visited (Table 1).
Timeline
It is essential to establish a travel
and exposure timeline, including details
related to the duration of the trip, timing
4 Critical Decisions in Emergency Medicine
■ CASE TWO
A 40-year-old man presents with
the sudden onset of fever, fatigue,
and myalgia, starting 2 days ago,
followed by vomiting, diarrhea,
and abdominal pain 1 day later.
Today, he has had bloody stools. The
patient explains that he returned
from Guinea in West Africa 10 days
ago, where he was volunteering in a
rural hospital.
of exposure, and timing of illness in
relation to travel. Some studies suggest
that longer trips are correlated with an
increased risk and incidence of illness.1
Furthermore, due to the variation
of incubation periods, the timing of
symptoms related to travel can help
measure a patient’s risk for certain
conditions.
Pre-Travel History
The emergency physician should
also evaluate a patient’s pre-travel
preparation. Travelers who visit a clinic
prior to departure are less likely to
present with fever, acquire malaria, or
experience severe disease than those who
depart without a pre-trip assessment.
When managing a case of suspected
malaria, for example, the clinician
should ask if the patient received
chemoprophylaxis at a travel clinic and
assess compliance with the prescribed
regimen.
In one case series of US civilians,
6% of patients with malaria
reported adherence to appropriate
chemoprophylaxis.4 It is important to
remember that a traveler who has taken
chemoprophylactic medications can still
acquire malaria, although the incidence
is less likely.
Other Historical Details
To further narrow the differential
diagnosis and risk stratify a case, the
emergency physician should seek to
identify possible exposures, such as
a history of freshwater swimming,
known ingestions of contaminated
food or water, interactions with farm
■ CASE THREE
A 50-year-old man presents
with a cough, shortness of breath,
and an associated fever. His
temperature is 39°C (102.2°F),
and he is tachycardic and
tachypneic with increased work of
breathing. His family reports that
he returned 7 days ago from a trip
to Saudi Arabia.
animals, or reported insect bites.5 Details
about a traveler’s accommodations and
activities can provide critical information,
as business travelers can experience
far different exposures than adventure
travelers or front-line humanitarian
workers. Possible risk factors should be
investigated: Did the patient have bed nets
or screens? Was the patient in a more rural
or urban environment? Was the patient
staying in a hotel, camping, or visiting
farms? These factors can suggest differing
susceptibilities to various infections.
Travelers who were visiting friends or
family are at increased risk for certain
illnesses due to increased exposure to local
populations.
In addition, the clinician should inquire
as to whether a patient sought medical
care overseas. Whether a patient went
to a clinic, local hospital, or purchased
medications from a local pharmacy can be
valuable information. In many countries,
antibiotics and other medications can be
purchased over-the-counter without a
prescription. This information can help
to explain a delayed or atypical clinical
presentation.
CRITICAL DECISION
How should suspected malaria
be approached, and what other
diseases should be considered?
Several epidemiological studies of
fever in returned travelers indicate that,
when a specific etiological diagnosis
is made, malaria (Figure 1) is the most
frequently identified illness.3,6,7 However,
differentiating malaria from other travel-
related systemic febrile illnesses can
be challenging due to the nonspecific FIGURE 1. Life Cycle of the Malaria Parasite
findings that are associated with this
condition.
Malaria, particularly in
uncomplicated infections, is
characterized by symptoms
similar to those of other minor viral
illnesses. 8 Early symptoms of uncompli­
cated cases include fever, malaise,
myalgia, headache, and chills. The classic
paroxysms of chills and fever followed
by diaphoresis are infrequently observed
with falciparum malaria infection. 2 The
nonspecific early findings of malaria
overlap significantly with other causes
of acute febrile illness in returned
travelers, such as dengue, chikungunya,
and Zika (Figure 2). Although myalgia
is common with malarial infections, it is
usually less severe than when associated
with dengue, and muscle tenderness is
less prominent with malaria than with
leptospirosis or typhus.8
Malaria is also less likely to present
with a rash than dengue, chikungunya,
Zika, typhus, enteric fever, or meningo­
coccal septicemia.8 Petechiae are often
associated with viral hemorrhagic disseminated intravascular coagulation Malaria is caused by Plasmodium
fevers (VHFs) but are rarely seen with (DIC).8 High fevers, splenomegaly, parasites spread via an Anopheles
malaria. Petechiae are only found in thrombocytopenia, mild jaundice, and mosquito vector. Five Plasmodium
severe falciparum malaria infections abdominal tenderness are commonly species cause the disease in humans:
associated with complications such as found. P. falciparum, P. vivax, P. ovale,
P. malariae, and P. knowlesi. Other
TABLE 1. Selected Infectious Diseases by Region confounding causes of acute febrile
Incubation Period Incubation Period Incubation Period Incubation Period
illness in the returned traveler are also
of <10 Days of <21 Days of >21 Days of Months vector-borne; for example, dengue,
Caribbean Chikungunya Leptospirosis Zika, yellow fever, and chikungunya
Dengue are all arboviruses whose primary
Zika vector is the Aedes aegypti mosquito.
Central Dengue Enteric fever Leishmaniasis Chagas disease
Details about the travel timeline
America Zika Leptospirosis Leishmaniasis
South Dengue Enteric fever Leishmaniasis Chagas disease and geographic area visited can
America Yellow fever Leptospirosis Leishmaniasis be particularly valuable. Although
Zika significant overlap exists in
South Central Chikungunya Enteric fever endemic areas of malaria, dengue,
Asia Dengue chikungunya, Zika, African trypano­
SARS
somiasis, and leptospirosis, a travel
Southeast Chikungunya Japanese Leishmaniasis Leishmaniasis timeline can help differentiate them.
Asia Dengue encephalitis
Chikungunya, dengue, and Zika
SARS Enteric fever
Leptospirosis have incubation periods of less than
Sub-Saharan Hemorrhagic Hemorrhagic Filariasis Filariasis 2 weeks, while the incubation period
Africa fevers fevers Leishmaniasis Leishmaniasis for malaria varies by species. The
Yellow fever Schistosomiasis incubation period for P. falciparum
Widespread Malaria HIV Hepatitis A, E Malaria is approximately 12 to 14 days,
Malaria HIV Tuberculosis
with a range from 7 to 30 days. The
Malaria
overwhelming majority of cases of

August 2018 n Volume 32 Number 8 5

 FIGURE 2. Global Distribution of Arboviruses
P. falciparum malaria occur within
1 month of return, but P. vivax and
P. ovale infections can present months
or even years after the initial infection.9
Complications of malaria can develop
rapidly and include encephalopathy,
hypoglycemia, acidosis, acute renal
failure, pulmonary edema, hepatic
dysfunction, intravascular hemolysis,
DIC, and shock. Because of the rapid
onset of complications, patients with
signs of severe disease or a parasite load
of greater than 5% should be treated
immediately with intravenous (IV)
antimalarial agents. Pregnant patients and
children are more susceptible to morbidity
and mortality related to malarial
infections; clinicians should be vigilant
when managing these patients, even those
with seemingly mild symptoms.
Malaria is diagnosed based on
demonstration of the parasite, which
is accomplished via thick and thin
blood smears or more advanced
methods, including rapid antigen tests
and polymerase chain reaction (PCR)
techniques.8 A febrile traveler who has
returned from an endemic area should
promptly have thick and thin blood
smears examined for the parasite, after
notifying the lab personnel about the
concern for the infrequently seen disease.
When suspicion is high and the
6 Critical Decisions in Emergency Medicine
parasite cannot be visualized, blood
smears should be repeated every 12 to
24 hours for 2 days.8 In cases of altered
mental status and fever after travel to
endemic areas, cerebrospinal fluid (CSF)
should be evaluated to rule out other
causes of encephalopathies; CSF in
patients with malaria is usually normal
or demonstrates nonspecific, mildly
elevated protein and mild pleocytosis.10
Treatment varies based on the
severity of the illness, drug susceptibility,
and species of parasite. Due to
increasing drug resistance in endemic
areas, the World Health Organization
(WHO) recommends artemisinin-based
compounds as the first-line therapy
for falciparum malaria infections.8,11
In addition to initial therapy to treat
erythrocytic forms, patients with
P. vivax or P. ovale infections require
primaquine to eradicate the dormant
liver hypnozoites and prevent relapse.8
The Centers for Disease Control
and Prevention (CDC) maintains a
24-hour malaria hotline, which provides
clinicians with diagnostic and treatment
advice from a Malaria Branch expert at
all times. The CDC Malaria Hotline can
be reached Monday through Friday from
9 AM to 5 PM EST at 855-856-4713;
for after-hours assistance with diagnosis
or management of suspected malaria
cases, health care providers can call the
CDC Emergency Operations Center at
770-488-7100.12
While no emergency treatment is
required, the clinical presentation of Zika
can overlap greatly with malaria and is
another important consideration in the
febrile returned traveler, particularly for
females of childbearing age. In cases of
suspected Zika, the emergency provider
should follow state guidelines for testing.
Although dengue, chikungunya, and Zika
have been specifically mentioned, other
diseases can present similarly. Therefore,
a broad differential diagnosis should
be considered in returned travelers who
present with acute febrile illness, including
acute HIV, enteric fever, leptospirosis,
African trypanosomiasis, yellow fever,
visceral leishmaniasis, hepatitis, influenza,
tick-borne rickettsioses, and many other
illnesses.
CRITICAL DECISION
What are the potential causes of
hemorrhagic fever, and how should
they be managed?
The WHO defines acute hemorrhagic
fever syndrome as an acute onset of fever
of less than 3 weeks duration in a severely
ill patient, plus any two of the following:
• Hemorrhagic or purpuric rash
• Epistaxis
• Hematemesis
• Hemoptysis
• Blood in stools
• Other hemorrhagic symptoms and no
known predisposing host factors for
hemorrhagic manifestations.13
Hemorrhagic fevers can be caused by
viral, bacterial, or rickettsial diseases.
Viral causes can be classified into the
following families: filoviruses (Ebola
and Marburg), arenaviruses (Lassa
fever, Junin, Machupo, Lujo, Sabia,
and Chapare), flaviviruses (yellow
fever, dengue, Omsk hemorrhagic
fever, Kyasanur Forest disease), and
bunyaviruses (Crimean-Congo hemorr­
hagic fever, Rift Valley fever, and
Hantaan hemorrhagic fever). Each
virus is associated with a specific
host species, and human infection is
incidental. These host-virus associations
generally limit the distribution of each
disease to specific geographical areas,
although travelers can carry disease to
nonendemic areas. Human-to-human
spread can cause significant outbreaks,
as exemplified by the recent Ebola
outbreak in West Africa.
Ebola Virus
Ebola virus disease sets itself apart
from other causes of hemorrhagic fever
by its virulence and mortality. Mortality
rates have reached as high as 70% to
90% in prior epidemics.15,16 Ebola viruses
are found in several African countries.
The infamous West African Ebola
epidemic of 2014 to 2015 turned the
virus into a household name.
The Ebola and Marburg viruses,
of the filovirus family, are among the
most virulent diseases in humans.16
Unlike other causes of VHF, the primary
reservoir for Ebola is uncertain, although
many believe that fruit bats serve this
role.17 Humans can contract the virus
through contact with infected bats,
primates, or other humans. Once humans
are infected, the disease can spread
rapidly. Human-to-human transmission
occurs through direct contact with bodily
fluids from an infected person, by objects
that have been contaminated with such
bodily fluids, and even through the semen
of males who previously recovered from
the disease.18,19
The combination of virulence and
mortality of both Ebola and other
causes of VHF makes transmission
prevention a critically important focus.
Early symptoms of VHF can be similar
to, and therefore difficult to distinguish
from, other febrile illnesses. During
an outbreak, febrile patients should be
routinely screened for travel to endemic
areas and symptoms concerning for VHF.
Clinicians must maintain a high degree of
suspicion in any patient who has recently
returned from an endemic area or has
had contact with someone with VHF who
presents with fever, muscle aches, severe
headache, diarrhea, vomiting, abdominal
pain, or any unexplained hemorrhage.
If VHF is suspected, extreme caution
must be taken to prevent transmission
within the health care facility. The
patient should immediately be placed
in an isolated room with a designated
bathroom or bedside commode. Health
care workers should act in designated
roles to minimize the number of workers
who manage the patient. All personnel
who come into contact with the patient
should wear appropriate personal
protective equipment, and interactions
should be recorded in a log.
For a comprehensive review of
appropriate personal protective
equipment, see the CDC guidelines
at http://www.cdc.gov/vhf/ebola/
healthcare-us/ppe/guidance.html. The
facility’s infection control program and
the local health department should be
notified, and a workup should continue,
using only dedicated equipment in
compliance with local protocols. For
further details on the approach to triage,
see the algorithm published by the CDC.20
If clinical suspicion remains high
after the initial evaluation, testing should
proceed in conjunction with the local
health department. Various forms of
testing are available, including PCR,
enzyme-linked immunosorbent assay
(ELISA), virus isolation, and IgM and IgG
for patients later in the disease course. For
most causes of VHF, no specific treatment
exists. Management should therefore
be supportive with IV fluids, electrolyte
replacements, supplemental oxygen,
vasopressors, and mechanical ventilation,
and combined with the treatment of other
infections, as needed.
Dengue Virus
Dengue virus infection is the most
common mosquito-borne illness
worldwide.21,22 Transmission is
ubiquitous throughout the subtropics
and tropics, with more than half the
world’s population at risk of infection.23
Manifestations of the infection can
range from acute febrile illness,
commonly referred to as dengue fever,
to dengue hemorrhagic fever and dengue
shock syndrome.
The Aedes aegypti mosquito
is the primary vector for dengue
virus transmission. The incubation
period ranges from 3 to 14 days,
but symptoms usually begin 4 to 7
days after being bitten by an infected
mosquito. Dengue fever can present as
an acute febrile illness; it is colloquially
referred to as “breakbone fever” due to
the associated arthralgia. The WHO
recommends considering this diagnosis
when fever is accompanied by two
or more of the following symptoms:
severe headache, retro-orbital pain,
joint pain, myalgia, nausea, vomiting,
swollen glands, or rash.24 Hemorrhagic
manifestations, such as epistaxis and
scattered petechiae, are seen in cases
of uncomplicated dengue infection;
however, they can also indicate more
severe disease. Patients with dengue
fever can also present with abdominal
pain, lethargy, restlessness, or elevated
liver transaminases, but these should
alert the provider to possible severe
dengue infection.
Symptoms of severe illness usually
manifest 2 to 5 days after the onset of
typical dengue fever.25 In addition to
fever, patients with hemorrhagic forms
of the disease exhibit the following
triad of features:
• Evidence of increased vascular
permeability
• Marked thrombocytopenia
(100,000 cells/mm3 or less)
• Spontaneous bleeding or signs of
hemorrhagic tendency26
When dengue is accompanied
by signs of circulatory failure (eg,
hypotension, narrow pulse pressure,
or weak pulses) in addition to features
of dengue hemorrhagic fever, the term
dengue shock syndrome is often used.
Historically, the virus has been classified
August 2018 n Volume 32 Number 8 7

FIGURE 3. Tourniquet Test
The tourniquet test is part of the new WHO case definition for dengue. The test, which
is a marker of capillary fragility, can be used as a triage tool to differentiate patients
with acute gastroenteritis, for example, from those with dengue. Note: Even if a
tourniquet test was previously done, it should be repeated if it was previously
negative or there is no bleeding manifestation.
How to perform the test:
1. Measure and record the patient’s blood pressure
(eg, 100/70).
2. Inflate the cuff to a point midway between SBP
and DBP; maintain for 5 minutes. (100 + 70) ÷ 2 =
85 mm Hg
3. Reduce and wait 2 minutes.
4. Count petechiae below the antecubital fossa
(see image).
A positive test is indicated by 10 or more
petechiae per 1 square inch.
into dengue fever, dengue hemorrhagic
fever, and dengue shock syndrome.
Although these terms are still frequently
used in clinical practice, nomenclature
has more recently been simplified to
dengue with or without warning signs
and severe dengue.26 In the updated
classification system, severe dengue fever
is defined by severe plasma leakage,
severe hemorrhage, and/or severe organ
impairment. Understanding both systems
can help the provider recognize signs of
more serious illness and communicate
effectively with consulting services.
Signs of increased vascular
permeability include pleural effusion,
ascites, or hemoconcentration, which can
be diagnosed with bedside ultrasound,
chest radiographs, or chest or abdomen
CT. These complications usually begin
3 to 7 days after the onset of typical
dengue fever, usually coinciding with the
time of defervescence. The sequelae of
profound vascular leakage can include
respiratory distress and overt shock.26
Hemorrhagic manifestations of dengue
virus include spontaneous bleeding,
generally petechiae or ecchymoses,
or evidence of hemorrhagic tendency.
Hemorrhagic tendency is demonstrated
by a positive “tourniquet test.” The test
(Figure 3) is performed by taking the
patient’s blood pressure and then inflating
the blood pressure cuff on the arm to
midway between the systolic and diastolic
blood pressures, keeping it inflated for
5 minutes. The pressure is then released
for 2 minutes. The skin beneath the
8 Critical Decisions in Emergency Medicine
cuff is examined for petechiae, and the
number of petechiae is recorded. The test
is considered positive if there are 10 or
more petechiae per 1 square inch of skin.
A positive test indicates microvascular
fragility and a hemorrhagic tendency.
Although dengue is generally a
clinical diagnosis, more advanced
confirmatory testing exists. Management
is supportive, consisting primarily of
volume resuscitation and analgesia. Pain
management should be achieved with
medications other than nonsteroidal
anti-inflammatory agents, as these are
contraindicated in cases of dengue fever.2
CRITICAL DECISION
What diseases should be
considered in a febrile returned
traveler with abdominal pain,
respiratory complaints, or
neurological symptoms?
For undifferentiated fevers in returned
travelers, the involved organ systems can
provide additional clues for diagnosis.
As with other travel-related illnesses,
it is essential to elicit a detailed travel
history to identify potentially important
exposures. Organ-specific signs and
symptoms can assist the clinician.
The approach to fever in the returned
traveler with abdominal pain, respiratory
symptoms, or neurological symptoms
should begin with the consideration of
nontravel causes, and then be expanded
to a differential diagnosis that includes
travel-related etiologies.
Abdominal Pain and Fever
Concerning features such as jaundice,
organomegaly, or hematochezia should
prompt the clinician to pursue an
expanded workup. Lab studies and
imaging — stool microscopy, stool
culture and sensitivity, stool ova and
parasites, stool serology, hemoccult
testing, blood cultures, or other
advanced diagnostic tools — should be
ordered as clinically indicated. Empiric
treatment can be indicated based on the
suspected diagnoses.
Aspects of a patient’s presentation
can guide the emergency provider to
narrow the differential diagnosis for
fever and abdominal pain. For example,
a chief complaint of watery diarrhea can
suggest enterotoxigenic Escherichia coli,
cryptosporidiosis, giardiasis, cholera,
or a rotavirus. A history of bloody
diarrhea can suggest an invasive or
inflammatory etiology, including both
bacterial and parasitic causes, such as
enterohemorrhagic E. coli, enteroinvasive
E. coli, Salmonella, shigellosis,
Campylobacter enteritis, Yersinia
enterocolitica, or Entamoeba histolytica.
However, these patients often present
with watery diarrhea as well.
Jaundice can imply etiologies such as
hepatitis, severe malaria, leptospirosis,
yellow fever, dengue, or other VHFs.
Organomegaly can suggest malaria,
leishmaniasis, amoebic liver abscesses,
enteric fever, brucellosis, schistosomiasis,
or hepatitis. Petechiae can be due to
leptospirosis, yellow fever, dengue,
or other VHFs. Abdominal pain and
fever accompanied by a rash should
alert the emergency physician to VHFs,
brucellosis, or enteric fever, among
other illnesses. Shigellosis should be
considered in patients with diarrhea,
febrile seizures, and a history of travel. In
patients with fever, abdominal pain, and
eosinophilia associated with pulmonary
symptoms, the clinician should consider
helminthic sources, such as hookworms
or roundworms.
Traveler’s Diarrhea
Diarrhea and gastroenteritis are
among the most common travel-related
complaints. Although it is important
to consider more concerning etiologies,
most patients with fever, abdominal
pain, and diarrhea are suffering from
traveler’s diarrhea, a mild and self-
limited disorder that generally resolves
within 3 to 7 days.27 Primary treatment is
targeted at fluid resuscitation, as needed.
Antibiotic and antimotility agents can be
used to limit the severity and duration of
symptoms. When there is suspicion for
enterohemorrhagic E. coli (eg, a history
of bloody stools), caution should be used,
as antibiotic treatment is associated with
an increased risk of hemolytic uremic
syndrome.
Bacterial and viral pathogens
associated with traveler’s diarrhea
generally have an incubation period of
6 to 72 hours; the incubation period
for protozoal pathogens is considerably
longer (typically 1-2 weeks). 27 Markedly
elevated fever and blood or pus in the
stool are uncommon and should raise
suspicion for another etiology.
Enteric Fever
Enteric fever, caused by Salmonella
Typhi or Salmonella Paratyphi, can
produce fever and abdominal pain
in the returned traveler, particularly
undifferentiated prolonged fever. The
presentation of the disease is somewhat
FIGURE 4. Lung X-Ray of a Patient with Q Fever
nonspecific. When suspicion exists,
malaria should be ruled out, and
other diagnoses should be considered,
including hepatitis, VHFs, bacterial
enteritis, dengue, brucellosis, rickettsial
infections, leptospirosis, amoebic liver
abscesses, acute HIV, cholera, amoebic
dysentery, and parasitic etiologies, such
as Giardia and Cryptosporidium.
The incidence of enteric fever is
highest in South and Southeast Asia,
but it should also be considered for
travelers returning from Africa, East
Asia, West Asia, Central America, and
South America.28,29 The incubation
period for the disease ranges from
5 to 21 days.30 Humans are the
only hosts of Salmonella Typhi and
Salmonella Paratyphi, and both ill and
asymptomatic chronic carriers can
shed bacteria in stool. Most cases are
transmitted via contaminated food
or water. However, transmission has
been described in health care workers
(exposed via both patient and specimen
contact) and also between male sexual
partners. 30
Risk factors for transmission include
the consumption of contaminated water
or ice, food washed in contaminated
water, raw fruits and vegetables
grown in fields fertilized with sewage,
food and drinks from street vendors;
flooding; and suboptimal hand-washing
practices. 30 Patients should be asked
about their immunization history, as
many travelers who acquire typhoid
fever have not been appropriately
immunized, and the vaccine can be less
than 75% effective.31
The initial presentation of enteric
fever is variable, but fever is generally
present in the early stages. Vital
signs can show relative bradycardia
compared to what is expected for
fever, sometimes referred to as pulse-
temperature dissociation or the Faget
sign. The classically described “rose
spots” of typhoid fever are groups
of faint, salmon-colored, blanching
maculopapules, primarily found on
the trunk; when present, they are
usually evident during the latter part
of the first week or during the second
week of infection. 30 Abdominal
pain, nausea, vomiting, anorexia,
hepatosplenomegaly, myalgia, and
headache can also be present. Patients
with severe infection can present with
gastrointestinal bleeding, intestinal
perforation with resulting peritonitis,
septic shock, or altered mental status. 30
A definitive diagnosis of Salmonella
Typhi or Salmonella Paratyphi is made
by isolation of the organism. The
physician should consider ordering stool
and blood cultures during the initial
evaluation. Stool cultures are often
negative during the first week of the
disease course, while blood cultures are
commonly positive.
An important treatment
consideration is the increasing rate
of multidrug-resistant strains of
Salmonella Typhi and strains with
decreased ciprofloxacin susceptibility. 30
For severe or complicated disease
courses, ceftriaxone is considered the
first-line empiric therapy. Antibiotic
therapy for uncomplicated disease
courses depends on the risk of antibiotic
resistance; azithromycin is typically
recommended for the empiric treatment
of enteric fever acquired in areas with
high fluoroquinolone resistance.
August 2018 n Volume 32 Number 8 9
 Respiratory Complaints
In one study, respiratory complaints
associated with fever occurred in
about one in seven cases of fever in the
returned traveler. 3 Although the vast
majority of cases are attributable to
common bacterial and viral pathogens,
it is important to note that travelers in
close contact with the local population,
such as those visiting family or staying
in relatives’ homes, are at an increased
risk for pneumonia and influenza,
as compared to tourists and business
travelers. 3 Some other considerations
include legionellosis, acute
schistosomiasis, Q fever, leptospirosis,
severe acute respiratory syndrome
(SARS), and Middle East respiratory
syndrome (MERS).
Patients with a history of travel that
includes farm work, particularly with
cattle, goats, or sheep, should be eval­
uated for acute Q fever caused by
Coxiella burnetii, which is typically
transmitted in aerosolized animal
excrement or contaminated soil (Figure 4).
Unpasteurized milk is another source.
Incubation is approximately 3 weeks,
and patients can present with pulmonary
symptoms, headaches, and other non­
specific signs. Emergency physicians should
also be aware that Q fever can progress to
endocarditis or vascular infections.32
TABLE 2. National Notifiable Travel-Related Diseases (2018)
Arboviral diseases Giardiasis
• California serogroup virus Hantavirus
• Chikungunya virus Hepatitis A
• Eastern equine encephalitis Hepatitis E
• Powassan virus HIV
• St. Louis encephalitis Malaria
• West Nile virus Meningococcal disease
• Western equine encephalitis Measles
Babeseosis Plague
Brucellosis Q fever
Campylobacteriosis Salmonellosis
Cholera Shigellosis
Cryptosporidiosis Tuberculosis
Dengue virus Tularemia
Note: This list is not comprehensive; follow local reporting protocols.
Data modified from the Centers for Disease Control and Prevention. https://www.cdc.
gov/nndss/conditions/notifiable/2018
10 Critical Decisions in Emergency Medicine
Adventure travelers, who participate
in boating and swimming activities in
Sub-Saharan Africa or Southeast Asia,
are at risk for Katayama fever due to
acute schistosomiasis. In these patients,
an immunological response to the
schistosomal worms can cause fever,
nonproductive cough, bronchospasm,
urticaria, fatigue, and organomegaly.
Pulmonary infiltrates on x-ray and
eosinophilia typically present 4 to 6
weeks after travel; the diagnosis is
primarily clinical.33,34
Recent years have seen outbreaks of
rapidly progressive respiratory distress
syndromes. Ongoing public health
syndromic surveillance and the use of
appropriate personal protection and
patient isolation can aid in the timely
diagnosis and prevention of further
disease spread. For the SARS outbreak
of 2002 to 2003, risk factors included
health care workers, work caring for
or slaughtering wildlife for human
consumption, male gender, advanced
age, and air travel. The coronavirus,
transmitted by aerosolized droplets, had
an incubation period of approximately
4 to 6 days; patients typically presented
with fever greater than 38°C (100.4°F)
and pneumonia or acute respiratory
distress syndrome (ARDS) on chest
radiograph.35,36
Typhoid fever
Vibriosis
Viral hemorrhagic fevers
• Crimean-Congo
• Ebola virus
• Lassa virus
• Lujo virus
• Marburg virus
• Guanarito virus
• Junin virus
• Machupo virus
• Sabia virus
Yellow fever
Zika virus
Similarly, the CDC currently
recommends that patients with fever
and pneumonia be assessed for Middle
East respiratory syndrome coronavirus
(MERS-CoV) if they have returned
from travel in the Arabian peninsula
within the last 14 days, if they:
• have had close contact with such a
traveler,
• are febrile with respiratory
complaints after spending time in
a health care facility (as a visitor,
employee, or patient) in a territory
where health care-associated cases of
MERS have recently been identified,
• or have had close contact with a
MERS patient.
Emergency physicians should follow
established guidelines for testing and
reporting in such cases.37
Neurological Complaints
Altered Mental Status
Altered mental status and fever
in travelers returning from malaria-
endemic regions requires emergent
evaluation for cerebral malaria,
bacterial meningitis, and encephalitis.
Venezuelan equine encephalitis,
Japanese encephalitis, and tick-borne
encephalitis should also be considered,
depending on the area of travel.
Tick-borne encephalopathies are most
common in Eastern European outdoor
adventurers. Neisseria meningitidis
should be considered for those patients
who have visited Sub-Saharan Africa’s
meningitis belt, which encompasses
26 countries from Senegal to Ethiopia;
however, outbreaks are sometimes seen
in other parts of the world.
Although a vaccine is now required
for Muslim pilgrims who travel to
Mecca, the vaccination does not cover
all strains; physicians should remain
alert for meningococcal meningitis.
Cryptococcal meningitis and tuberculous
meningitis are further considerations
when assessing immunocompromised
patients with prolonged travel and those
who have lived among local populations
in Sub-Saharan Africa.
Seizure
The two most common causes of
seizures worldwide, neurocysticercosis
and schistosomiasis, can present
with fever, but they are uncommon
in casual travelers.38 Seizures with
febrile diarrheal illness should raise
concern for shigellosis. Patients who
present with febrile seizures after
travel to endemic areas should also be
evaluated for Japanese encephalitis,
dengue hemorrhagic fever, and cerebral
malaria.38 Japanese encephalitis is a
mosquito-borne flavivirus that is vaccine
preventable. Travelers to rural and
periurban areas in Southeast Asia and
the Western Pacific are at the highest
risk of exposure. Although only 1 in
250 infections causes serious clinical
disease, such cases can be heralded by
fever, headaches, seizures, parkinsonian
features, and even coma. In severe
disease courses, the case fatality rate
reaches 30%; up to another 30%
of patients experience permanent
neuropsychological problems.39,40
Diagnosis is based on serologic
and CSF confirmatory studies, and
treatment is symptomatic. Refer to
the previous discussions on dengue
shock syndrome and malaria for
further information. Remember that
pregnant women, children, nonimmune
populations, and those taking inadequate
chemoprophylaxis are at increased risk
for cerebral malaria.
CRITICAL DECISION
Which diseases must be reported
to the CDC?
In the interest of public health, the
CDC must be informed of the diagnosis
of several infectious diseases. It is the
responsibility of the provider, not the
patient, to notify the CDC. Such diseases
are designated as either reportable or
notifiable. It is mandatory to report
cases of any disease with a reportable
n Neglecting to ask about recent travel or collect a thorough travel history.
n Ignoring personal safety precautions and appropriate isolation procedures.
n Failing to follow appropriate reporting protocols.
n Failing to recognize patients at increased risk for more severe disease,
including children, pregnant women, elderly patients, and immuno­-
com­promised individuals.
n Review assessments for international travel screening or other CDC and
WHO information to help identify high-risk patients.
n Infections with seasonal fluctuations can present at atypical times due to
varying times of transmission in other geographic areas.
n If initial testing is negative, patients with suspected malaria should undergo
repeat blood smears within 12 to 24 hours of presentation, as sensitivity
improves with repeated tests.
n When malaria has been excluded, consider enteric fever for cases of
prolonged fever.
designation; reporting a notifiable diseases, as compiled by the CDC,
disease is voluntary. Each state that are unique to the returned
determines what diseases fall under traveler.
each category, so reportable diseases Summary
are unique to each state. Providers, While travel-related diseases are
hospitals, and laboratories should report uncommonly seen in US emergency
cases to the local health department, departments, prompt recognition
which then shares the information and appropriate management are
with the CDC. Some laboratories essential for the safety of patients
automatically report positive results, but and the public. Emergency physicians
providers should familiarize themselves must be adept at taking a complete
with the procedures in their individual travel history, including prophylaxis
practice settings. and immunizations, and should be
Reporting cases of certain infectious comfortable forming an appropriate
diseases serves many purposes, most differential diagnosis.
importantly helping to slow the Travel history, incubation period,
spread of communicable diseases. and organ-system involvement should
This information also facilitates lead physicians toward specific
surveillance, which can help to identify diagnoses. An increased index of
sources of outbreaks; allows public suspicion should be maintained for
health organizations to plan preventive patients with higher-risk exposures,
measures and control strategies; and such as adventure travelers,
expedites the initiation of appropriate humanitarian workers, those visiting
treatment options. Specific diseases friends and relatives, and those with
receive reportable designations based fevers lasting longer than 1 week. In
on virulence, communicability, and the addition, physicians must ensure that
potential for morbidity and mortality. patients are appropriately isolated,
Table 2 lists notifiable infectious personal protection protocols are
followed, and specific diseases of
concern are reported to the CDC.
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The emergency physician
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■ CASE THREE
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 The Critical Procedure
Temporomandibular Joint Reduction
Temporal bone
Articular
eminence
Glenoid
fossa
Mandibular condyle
DISLOCATION REDUCTION
Dislocation at the temporomandibular joint (TMJ) is caused by dislocation of the mandibular condyle(s).
The disorder is commonly precipitated by trauma or excessive opening of the mouth. Spasms of the
mastication muscles of the jaw, including the masseter, temporalis, and internal pterygoid, result in
trismus and must be overcome for reduction to occur. Anatomically, the mandibular condyle generally
becomes fixed in the anterior-superior aspect of the articular eminence.
Benefits and Risks
TMJ reduction in the emergency department is a quick
procedure that can alleviate a patient’s discomfort and anxiety.
Its primary risks include injury to the person performing the
procedure or further injury to the patient. Other risks include
adverse effects caused by medications or sedation administered
prior to or during the procedure.
Since the clinician’s fingers or hands are often positioned
intraorally and the muscles of the jaw are quite strong, a
patient’s tooth can puncture the glove or skin. Loose dentition
or dental hardware can be damaged during the process.
Finally, the possibility of iatrogenic damage to the bone and
surrounding tissues during reduction should be considered.
Alternatives
In addition to the intraoral technique previously described,
an extraoral method can facilitate TMJ reduction. For the
extraoral technique, the clinician massages over the dislocated
condyle and muscles to relax the spasm and direct the
dislocation back to the joint space. A local anesthetic can be
used as an adjunct and injected toward the lateral pterygoid
and into the joint space. Surgical repair may be considered if
external reduction cannot be achieved.
Reducing Side Effects
Contraindications to the procedure include severe facial
trauma and fracture of the mandible. To reduce the risk of
clinician injury, some providers wrap their fingers with gauze
and/or place a tongue depressor (cut in half) or finger splints
between digits and dentition. Alternatively, the mandibular
By Michael Gibbons, MD, MBA
Dr. Gibbons is an attending physician in
the Department of Emergency Medicine at
Putnam Community Medical Center
in Palatka, Florida, and North Florida
Regional Medical Center in Gainesville.
Reviewed by Steven Warrington, MD, MEd
NORMAL
ridge can be used as a resting point, instead of the teeth.
Proper positioning and preparation can also improve the odds
of success and decrease the risks that can arise from sedation
or intraoral manipulation.
Special Considerations
Cases that involve extensive facial trauma, mandibular
fractures, or extensive dental hardware should be discussed with
a consultant regarding the optimal treatment plan. However, the
patient’s pain and anxiety should be considered while defining
that plan. After closed reduction, it is important to advise patients
to implement a soft diet and avoid extreme opening (eg, yawning)
while the jaw heals (approximately 1 week). Additionally, some
patients may benefit from a nonsteroidal anti-inflammatory agent
and/or a wrap that helps keep the jaw closed.
TECHNIQUE
1. Position the patient in the supine/recumbent or sitting
position, with the back resting against the bed.
2. Provide sedation and/or an anxiolytic agent; consider
adjunctive local anesthesia.
3. Apply gauze (over your glove) to digits that will be
positioned intraorally, generally thumb(s). Prior to
applying the gauze, consider applying half of a tongue
depressor along the palmar surface of the thumb that will
be in contact with the patient’s teeth.
4. Apply consistent, downward traction with slight flexion
and posterior displacement.
August 2018 n Volume 32 Number 8 13

Venous thromboembolism
(VTE), which includes deep vein
thrombosis (DVT) and pulmonary
embolism (PE), is the leading cause
of morbidity and mortality in
pregnant women in the developed
world. Although the absolute incidence
of VTE in pregnancy is 1 to 2 per
1,000, this risk is 5 times higher than
in nonpregnant patients. Most VTEs
during pregnancy occur within the first
20 weeks of gestation, but the overall
incidence is greatest during the first
6 weeks postpartum. DVTs in pregnant
women are more likely to be in the
left leg (85% in the left leg versus
55% in the right leg) and proximal in
the iliofemoral region (72% proximal
versus 9% distal). The strongest
predictive risk factor is previous VTE
in pregnancy. Other risk factors include
venous stasis, immobilization, elevated
BMI, and dehydration from emesis.
Suspected DVT is best assessed
with serial compression duplex
ultrasonography; one prospective study
demonstrated a negative predictive
value of 99.5%. If the initial ultrasound
examination is negative but clinical
suspicion remains high, it is safe to
repeat the examination in 3 to 7
Critical Decisions in Emergency Medicine’s series of LLSA reviews features articles from ABEM’s 2018 Lifelong Learning and
Self-Assessment Reading List. Available online at acep.org/llsa and on the ABEM website.
14 Critical Decisions in Emergency Medicine
The LLSA
Literature Review
Venous Thrombosis
in Pregnancy
By Eric Vaught, MD, MC, LT; and Daphne Morrison Ponce, MD, LCDR
Naval Medical Center, Portsmouth, Virginia
Reviewed by Andrew J. Eyre, MD, MHPEd
Greer IA. Pregnancy complicated by venous thrombosis. N Engl J Med. 2015 Aug 6;373(6):540-547.
days with no interim anticoagulation for suspected DVT, as these two
treatment. Iliocaval venous thrombosis conditions often arise concurrently. If
is usually extensive and is often a patient with PE symptoms has a DVT
identified with compression ultra­ identified with ultrasound, no further
sonography; however, MRI or x-ray imaging is needed and the diagnosis
venography can be considered for of PE can be made empirically. As in
evaluation if suspicion is high. nonpregnant patients, clinical suspicion
The majority of pregnant patients for PE should be heightened for those
with PE also have DVT. A PE whose ECG shows sinus tachycardia or
imaging workup can begin with the right heart strain.
same compression ultrasound used Oxygen saturation is an unreliable
KEY POINTS
n DVTs in pregnancy are more likely to be proximal and in the left leg. The
diagnostic test of choice is serial compression duplex ultrasonography.
n If a DVT is identified in a patient with PE symptoms, no further imaging is
needed, and empiric treatment should begin.
n VQ scans and CTPA have similar negative predictive values (100% and 99%,
respectively). VQ scans emit a fetal radiation dose of 0.5 mGy, and CTPA
emits a fetal radiation dose of 0.1 mGy. Both tests fall below the estimated
level for teratogenesis and childhood cancer.
n CTPA can be used in patients with an abnormal chest x-ray or indeterminate
VQ scan, or if there is concern for other etiologies.
n LMWH is the first-line treatment for VTE in pregnancy. There is no evidence
to support an optimal dosing regimen for pregnant patients.
n Warfarin can be used in the postpartum period but should not be used in
pregnant patients. Direct thrombin inhibitors and antifactor Xa inhibitors
are contraindicated.
n Thrombolysis is indicated for the management of hemodynamically
unstable PEs or for DVTs that threaten leg viability.
diagnostic tool in pregnant or
postpartum women. Similarly, D-dimer
levels are not sensitive or specific
enough to aid in the diagnosis. There
is limited clinical data to support the
validity of the Modified Wells’ Criteria
for Pulmonary Embolism and LEFt
clinical prediction tools (left leg >2-cm
difference, edema, and first trimester)
for diagnosing pregnant patients
with VTE.
If further imaging is required to
assess for PE, radiation exposure to the
fetus must be minimized. It is estimated
that 1 mGy of radiation exposure
in utero increases the risk of fatal
childhood cancer by 0.006%. Chest
radiography emits more than 0.1 mGy
of radiation; however, x-ray findings
can have limited clinical utility in
assessing for PE. Ventilation-perfusion
(VQ) scans have a high negative
predictive value and are commonly
performed after a normal chest x-ray.
Computed tomographic pulmonary
angiography (CTPA) is useful if the
VQ scan is indeterminate, or if other
diagnoses are suspected.
Both tests minimize radiation to
the fetus (CTPA = 0.1 mGy versus VQ
scan = 0.5 mGy) and are well below the
radiation threshold for teratogenesis.
To further decrease radiation exposure,
the ventilation portion of the VQ scan
can be omitted without decreasing the
negative predictive value. CTPA scans
emit a maternal dose of 20 mGy to
breast tissue, which is 20 to 100 times
higher than VQ scan radiation; this risk
can be mitigated with breast shields.
The treatment for VTE in pregnancy
is low molecular-weight heparin
(LMWH), which is more effective
and has a better safety profile than
unfractionated heparin in this patient
population. Warfarin is contraindicated
due to teratogenicity. The ideal dosing
regimen for LMWH is unknown,
and data is insufficient to support
specific regimens in pregnant patients.
Therefore, enoxaparin (either 1 mg/kg
twice daily or 1.5 mg/kg once daily,
based on either prepregnancy or
current weight) is acceptable. Other
appropriate dosing regimens include
dalteparin (200 IU/kg once daily or
100 IU/kg twice daily) or tinzaparin hemodynamic compromise or for DVTs
(175 units/kg daily). There is no data that are threatening leg viability. Caval
to support tracking antifactor Xa levels filters can be used for recurrent PEs,
while a patient is taking LMWH. despite adequate anticoagulation or
LMWH should be stopped 24 hours if anticoagulation is contraindicated.
before delivery or neuraxial anesthesia, Elastic compression stockings provide
and when labor starts or is suspected. symptomatic relief only in patients
Anticoagulation can be restarted with DVT.
4 hours after delivery or after the The views expressed in this article are those of
epidural catheter has been removed.
the authors and do not necessarily reflect the
official policy or position of the Department of
Anticoagulation is continued for the Navy, Department of Defense or the United
States Government.
at least 6 weeks postpartum (for a
***
minimum total of 3 months). Warfarin We are military service members. This work was
may be used in the postpartum period. prepared as part of our official duties. Title 17
U.S.C. 105 provides that “Copyright protection
Oral direct thrombin inhibitors and
under this title is not available for any work of
antifactor Xa inhibitors should be the US Government.” Title 17 U.S.C. 101 defines
avoided, as they cross the placenta and a US Government work as a work prepared by
a military service member or employee of the
have adverse effects. Thrombolysis is
US Government as part of that person’s official
reserved for life-threatening PEs with duties.
Factors That Increase VTE Risk in Pregnant Patients
STASIS
• Compression of iliac
veins
• Right iliac artery over
left iliac vein
• Gravid uterus
• Hormonally mediated
vein dilation
• Immobilization
VASCULAR DAMAGE HYPERCOAGULABLE BLOOD
• Vascular • á Procoagulant factors
compression at á Fibrogen, factor V, IX, X, and VIII concentrations
delivery • â Anticoagulant activity
• Assisted or â Protein 5 concentration
operative delivery
á Activated protein C resistance
• â Fibrinolytic activity
á PAI-1 and PAI-2 activity
â tPA activity
• More thrombin generation
• Less clot dissolution
August 2018 n Volume 32 Number 8 15
 The Critical Image
A 30-year-old woman (G2 P2) with a history of ovarian cysts presents By Joshua S. Broder, MD, FACEP
with 2 days of left lower-quadrant abdominal pain. The pain was Dr. Broder is an associate professor and the
residency program director in the Division
initially sharp, crampy, and intermittent but has now become constant. It of Emergency Medicine at Duke University
is unaffected by eating. The patient reports nausea and vomiting; her last Medical Center in Durham, North Carolina.

normal bowel movement was 24 hours before her emergency department Case contributor: Brandon Ruderman, MD

visit. She denies fever, urinary symptoms, or vaginal bleeding or discharge.

The patient’s vital signs are blood pressure 126/70, heart rate 97, respiratory rate 16, temperature 35.8°C (96.4°F), and oxygen
saturation 100% on room air. She appears uncomfortable, and her left abdomen is tender to palpation, without rebound or
guarding. Her pelvic examination is normal. Her laboratory tests, including urinalysis, liver function, lipase, and WBC count,
are normal. A urine hCG test is negative.
The emergency physician suspects ovarian torsion or a cyst. A pelvic ultrasound is performed, which shows bilaterally normal
ovaries with normal blood flow. The patient continues to complain of severe pain, and a CT scan of the abdomen and pelvis
with intravenous contrast is performed.

A
Normal A-C. Axial, coronal, and sagittal CT images,
small bowel Target sign, soft-tissue window. Enlarged panels are provided
indicating for each to highlight the abnormal findings. In the
bowel left abdomen, a segment of small bowel is seen
within bowel telescoped within the surrounding small bowel. The
proximal small bowel is not dilated, and therefore
does not suggest accompanying obstruction.

Normal
small
bowel

Intussuscepted
segment, with
bowel within
bowel

16 Critical Decisions in Emergency Medicine

KEY POINTS typically can be reduced nonsurgically postoperative adhesions, and
using an air-contrast enema. Although even devices such as feeding
n Adult intussusception is rare; the
enterocolic intussusception can occur tubes.4 One retrospective study
incidence in one study was 37 (0.05%)
in adults, more proximal enteroenteric suggests that intussusceptions
per 69,040 abdominopelvic CTs
intussusceptions frequently make shorter than 3.5 cm are likely to
perform­ed over 4 years.1 In another
this reduction technique difficult or be self-limited and more likely
study, 45 cases of adult intussuscep­
impossible. Moreover, underlying to be benign.1 Other studies
tion (0.08%) were identified in 58,000
malignancy reportedly accounts suggest that short segment
surgeries over 12 years.2
for 16% to 65% of adult cases; as a intussusceptions with a narrow
n Pediatric intussusception is often
consequence, surgical reduction diameter and without obstruction
clinically suspected based on some with or without resection of the are less likely to harbor
combination of the classic triad affected bowel segment is frequently underlying pathology. However,
of intermittent pain, bloody stool, performed.1-4 the rarity of the condition limits
and palpable mass; ultrasound n Other causes of adult intussuscep­ study and requires clinical
is commonly used as a targeted tion include inflammatory bowel judgment for each case to
imaging technique. In contrast, adult disease, Meckel’s diverticulum, determine the need for surgery.5,6
intussusception is usually identified
incidentally during CT performed to
C
evaluate for other potential causes
of abdominal pain. Some patients
present multiple times and undergo
multiple imaging studies before
the diagnosis is made, suggesting
that adult intussusception is often
intermittent.
n Imaging findings in adults are
similar to those seen in children
with intussusception; in adults, CT Intussuscepted
images through the short axis of the segment,
bowel show a target sign with the with bowel
invaginated
intussusceptum visible within the
within bowel
concentric surrounding small or large
bowel (intussuscipiens). Evidence
of proximal obstruction may be
present, in which case the diameter
of the proximal small bowel will
exceed 2.5 to 3 cm. The diagnosis of
intussusception does not require the
administration of enteric contrast.
n The treatment of adult
intussusception differs from that of
pediatric cases. In children, ileocolic
intussception is common and

CASE RESOLUTION
The patient underwent laparoscopy, which confirmed an intussuscepted segment of jejenum in the
left hemiabdomen. The bowel was reduced and appeared viable, but given the high risk of underlying
pathology, a 15-cm segment of bowel, including the previously intussuscepted region, was resected.
Pathology tests did not reveal any abnormalities, and the patient recovered uneventfully.

1. Lvoff N, Breiman RS, Coakley FV, Lu Y, Warren RS. Distinguishing features of self-limiting adult small-bowel intussusception identified at CT. Radiology. 2003 Apr;227(1):68-72.
2. Huang WS, Changchien CS, Lu SN. Adult intussusception: a 12-year experience, with emphasis on etiology and analysis of risk factors. Chang Gung Med J. 2000 May;23(5):284-290.
3. Yalamarthi S, Smith RC. Adult intussusception: case reports and review of literature. Postgrad Med J. 2005 Mar;81(953):174-177.
4. Marinis A, Yiallourou A, Samanides L, et al. Intussusception of the bowel in adults: a review. World J Gastroenterol. 2009 Jan 28;15(4):407-411.
5. Tresoldi S, Kim YH, Blake MA, et al. Adult intestinal intussusception: can abdominal MDCT distinguish an intussusception caused by a lead point? Abdom Imaging. 2008
Sep-Oct;33(5):582-588.
6. Kim YH, Blake MA, Harisinghani MG, et al. Adult intestinal intussusception: CT appearances and identification of a causative lead point. Radiographics. 2006 May-Jun;26(3):733-744.

August 2018 n Volume 32 Number 8 17

 A 32-year-old woman with dyspnea.

The Critical ECG

Sinus rhythm, rate 84, acute pericarditis. Diffuse ST-segment elevation (STE) By Amal Mattu, MD, FACEP
is present on this ECG. Although there are many conditions that can induce Dr. Mattu is a professor, vice chair, and
director of the Emergency Cardiology
STE on the ECG, the major diagnostic considerations in patients with diffuse
Fellowship in the Department of
STE are large acute myocardial infarction, acute pericarditis, benign early Emergency Medicine at the University
repolarization, and left ventricular hypertrophy (LVH). LVH can be excluded of Maryland School of Medicine in
Baltimore.
by lack of voltage criteria. Of the remaining three considerations, acute
pericarditis is the only one that causes PR-segment depression/downsloping,
which is found in lead I and in the anterior and lateral precordial leads.

From Mattu A, Brady W. ECGs for the Emergency Physician 2. London: BMJ Publishing; 2008. Reprinted with permission.

18 Critical Decisions in Emergency Medicine

 Feeling No Pain
Procedural Sedation

LESSON 16

By Sana Shahbaz, MD; and Sean Kivlehan, MD, MPH

Dr. Shahbaz is an emergency medicine fellow at the South Asia Institute at
Harvard University in Cambridge, Massachusetts. Dr. Kivlehan is the director
of the International Emergency Medicine Fellowship in the Department of
Emergency Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.
Reviewed by David J. Pillow, Jr, MD, FACEP

OBJECTIVES
On completion of this lesson, you should be able to:
1. Describe procedural sedation, including its indications and
contraindications.
2. Discuss the different levels of sedation achieved through
procedural sedation.
3. Evaluate the various drug options available for procedural
sedation.
4. Explain whether fasting is necessary prior to procedural
sedation.
5. Anticipate, identify, manage, and minimize the
complications of procedural sedation.
6. Perform safe procedural sedation in pregnant women.
FROM THE EM MODEL
19.0 Procedures and Skills Integral to the Practice
of Emergency Medicine
19.3 Anesthesia and Acute Pain Management
19.3.3 Procedural sedation
CRITICAL DECISIONS
n What levels of sedation can be achieved with
procedural sedation?
n What are the indications and contraindications
for procedural sedation?
n What prerequisites, precautions, and preparations
are required for procedural sedation?
n Is fasting a prerequisite for procedural sedation?
n Which procedural sedation medications are safe
to use with pregnant patients?
n How can the complications of procedural sedation
be managed?
n What are the indications, contraindications, and
doses of drugs used for procedural sedation?

Because emergency physicians manage a spectrum of acute medical and traumatic conditions, they often
perform painful procedures that require sedation. Procedural sedation and analgesia (previously known as
conscious sedation) involves the use of several medications, including sedatives, dissociative agents, and/or
analgesics.1 When aptly performed, the process reduces the pain and anxiety caused by invasive and noninvasive
procedures, thus improving the experience for both the patient and clinician.2

August 2018 n Volume 32 Number 8 19

 CASE PRESENTATIONS
■ CASE ONE
A 26-year-old man presents after
slipping and falling onto his shoulder.
X-rays confirm a dislocated right
shoulder without any fractures. He is
given analgesia for pain management,
while the emergency physician
prepares for a shoulder reduction.
On examination, the patient’s
neurovascular status is intact in the
affected extremity, his vital signs are
normal, and his pain score improves
from an initial 7 out of 10 to a 5 out
of 10.
■ CASE TWO
A 70-year-old man is brought
in by paramedics after falling at
home. His trauma survey is normal;
examination of his right leg shows
Because the appropriate regimen varies
based on the specifics of each case,
emergency physicians must thoroughly
understand the advantages and
disadvantages of these medications and
be prepared to choose the most effective
agent, administer it safely, and anticipate
potential complications.
CRITICAL DECISION
What levels of sedation can
be achieved with procedural
sedation?
Procedural sedation and analgesia
— as defined by the American College
of Emergency Physicians (ACEP),
American Society of Anesthesiologists
(ASA), and Centers for Medicare and
Medicaid Services (CMS) — is the
technique of administering sedatives
or dissociative agents, with or without
analgesics, to induce an altered state
of consciousness, while preserving
cardiorespiratory function.2-4 During the
process, patients reach different levels
of sedation, depending on the dose, type
of medication, and response to the drug
(Figure 1). Sedation depths are part of
a continuum, ranging from minimal
sedation to general anesthesia. However,
ketamine is unique in that it is the only
agent that produces dissociative sedation.
20 Critical Decisions in Emergency Medicine
an internally rotated hip and foot.
His neurovascular status is intact. His
blood pressure (BP) is 140/100; his
vital signs are otherwise normal. His
medical history includes hypertension,
coronary artery disease, and congestive
heart failure. X-rays of the hip show
a posterior hip dislocation but no
fracture.
Acetaminophen and oxycodone are
administered for pain, while informed
consent is obtained. The patient is
then taken to the resuscitation room
to undergo hip reduction; he receives a
pretreatment of fentanyl as an analgesic
and propofol as a sedative. The hip is
successfully reduced, but soon after
the procedure, the patient desaturates
and becomes hypotensive. His oxygen
saturation level falls to 88%, and his
BP plummets to 80/60. The physician
Patients respond to medications
differently, so levels of sedation vary
based on the circumstances. A clear line
between these states often does not exist,
so clinicians must be prepared to manage
patients as they transition between
different sedation depths.
Minimal Sedation
Minimal sedation describes a patient
with a near-baseline level of alertness,
who retains the ability to respond
normally to verbal commands. Although
cognitive function and coordination
may be impaired, ventilatory and
cardiovascular functions are unaffected.
In the emergency department, minimal
sedation is commonly administered to
facilitate minor procedures.
Moderate Sedation
With moderate sedation, a patient
responds purposefully to verbal
commands alone or when accompanied
by light touch. Droopy eyelids or slurred
speech with delayed verbal responses
also can be noted. Protective airway
reflexes and adequate ventilation are
maintained without intervention, and
cardiovascular function remains stable.
Patients frequently experience amnesia
about the experience.
initiates small boluses of IV normal
saline and high-flow oxygen via face
mask.
■ CASE THREE
A 22-year-old woman, who is
20 weeks pregnant, presents after
twisting her left ankle while walking
down the stairs. Her trauma survey
is normal, except for the deformed
joint that needs reduction. She has no
medical history and is hemodynamically
stable. No neurovascular compromise
is found. After obtaining informed
consent, the patient is transferred to
the resuscitation room to undergo
ankle reduction. Anxious to minimize
the side effects in both the mother and
fetus, the emergency physician reviews
the options for procedural sedation in
pregnant patients.
Dissociative Sedation
Dissociative sedation creates a
unique, trance-like state in which
a patient experiences profound
analgesia and amnesia but
retains airway protective reflexes,
spontaneous respiration, and
cardiopulmonary stability. Ketamine
is the pharmaco­logical agent used to
produce dissociative sedation.
Deep Sedation
With deep sedation, a patient
cannot be easily aroused but responds
purposefully to noxious stimulation.
Assistance may be needed to ensure
that the airway is protected and
adequate ventilation is maintained.
Cardiovascular function is usually
stable; however, the patient must be
closely monitored for any changes
in ventilatory or cardiovascular
function.
General Anesthesia
With general anesthesia, a patient
is completely unresponsive to painful
stimuli and often requires assistance
to protect the airway and maintain
ventilation. Cardiovascular function
may be impaired.
CRITICAL DECISION Contraindications vary according to
the type of procedure and the age and
What are the indications and
comorbidities of the patient. Pulmonary
contraindications for procedural
diseases such as chronic obstructive
sedation? pulmonary disease (COPD), ischemic
Procedural sedation can be used cardiac disease, heart failure, anemia, and
in the emergency department for any neuromuscular diseases all increase the
procedure that causes pain or anxiety associated risks of procedural sedation.
in the patient. Common procedures Emergency physicians should be aware
requiring procedural sedation include not only of a patient’s chronic conditions,
fracture reduction and dislocation, but also of acute presentations that can
foreign body removal, laceration affect the safety of the sedated patient,
repair (particularly in young children), including hypovolemia, renal failure, and
abscess drainage, lumbar puncture, acute respiratory infections.
endoscopy, bronchoscopy, and electrical Drug allergies can typically be averted
cardioversion. Procedural sedation can by using different medications, but the
also facilitate diagnostic evaluations with physician should anticipate and prepare
CT or MRI, as well as burn dressing to address a difficult airway. The ASA’s
changes and the placement of chest tubes physical status classification system
and central catheters.5 quantifies the risks into a meaningful
TABLE 1. ASA’s Physical Status Classification System
Definition Examples (Including But Not Limited To)
Class I A normal healthy Healthy, nonsmoking, and no or minimal alcohol use
patient
Class II A patient with mild Mild diseases only, without substantive functional
systemic disease limitations. Current smoker, social alcohol drinker,
pregnant, obese (BMI 30-39.9), well-controlled diabetes
mellitus or hypertension, or mild lung disease
Class III A patient with severe Substantive functional limitations, with one or more
systemic disease moderate to severe diseases. Poorly controlled
diabetes mellitus or hypertension, COPD, morbid
obesity (BMI ≥40), active hepatitis, alcohol depen­
dence or abuse, implanted pacemaker, moderate
reduction of ejection fraction, end-stage renal disease
undergoing regularly scheduled dialysis, premature
infant with post-conceptional age <60 weeks, history
(>3 months) of myocardial infarction, cerebrovascular
accident, transient ischemic attack, or coronary artery
disease/stents.
Class IV A patient with severe Recent (<3 months) myocardial infarction,
systemic disease that cerebrovascular accident, transient ischemic attack,
is a constant threat or coronary artery disease/stents, ongoing cardiac
to life ischemia or severe valve dysfunction, severe reduction
of ejection fraction, sepsis, disseminated intravascular
coagulation, acute respiratory distress syndrome, or
end-stage renal disease not undergoing regularly
scheduled dialysis
Class V A moribund patient Ruptured abdominal/thoracic aneurysm, massive
who is not expected trauma, intracranial bleed with mass effect, ischemic
to survive without the bowel in the face of significant cardiac pathology, or
operation multiple organ/system dysfunction
Class VI A declared brain-dead
patient whose organs
are being removed for
donor purposes
predictive value (Table 1). For example,
ASA class I and II patients have a low
risk of complications, but keep in mind
that risks rise with deeper levels of
sedation.
Anticipating Difficult Airways
Before procedural sedation, all
patients should undergo a difficult-
airway assessment, and information
should be gathered about any previous
experience with sedation and analgesia.
A history of a difficult or failed airway,
or difficult bag-valve-mask ventilation,
is a strong risk factor for complications;
however, this information is frequently
unavailable. One study identified the
following five factors as independent
predictors of difficult bag-valve-mask
ventilation: age greater than 55 years,
body mass index (BMI) greater than
26 kg/m2, presence of a beard, absence
of teeth, and a history of snoring.6
Additional difficult-airway risk factors
include a short neck, micrognathia, a
large tongue, trismus, morbid obesity,
and anatomical abnormalities of the
airway and neck.7
The Mallampati classification
system is a simple assessment tool that
correlates visualization of anatomical
oropharyngeal structures to intubation
difficulty (Figure 2). The Mallampati
score is one component of a commonly
used mnemonic device — LEMON
— to predict potential complications
(Table 2).8,9 If a difficult airway or
difficult mask ventilation is anticipated,
anesthesia should be consulted; in such
cases, it may be optimal to perform the
procedure in the operating room.
Age Considerations
In children, active upper-respiratory
infections and asthma significantly
increase the risk of laryngospasm, which
should factor into the decision to sedate.5
No upper age limit for procedural
sedation exists, but the elderly have
a higher risk of complications due to
several factors, including increased
drug sensitivity and interactions with
chronic medications. Additionally, the
higher prevalence of cardiovascular and
pulmonary diseases in geriatric patients
increases the likelihood of hemodynamic
instability and respiratory difficulty.10
Reducing both the dose and frequency
August 2018 n Volume 32 Number 8 21
 FIGURE 1. Safely Sedated — States of Consciousness Vary When Patients Get Anesthesia

General Deep sedation Moderate Minimal Regional Local anesthesia

anesthesia Patients sleep sedation sedation anesthesia An anesthetic
Patient is through surgery Patients feel Patients feel Injection near a drug is usually
unconscious. with little drowsy and may relaxed and cluster of nerves injected into the
Gases or vapors memory of the sleep through may be awake. numbs the area tissue to numb the
are inhaled procedure upon the procedure. They can answer that requires specific location
through a waking. Breathing Patients awaken questions and surgery. Patients requiring minor
breathing mask can slow, and when spoken to or follow a physician’s stay awake or are surgery.
or tube, and other supplemental touched. Memory instructions. given a sedative.
drugs are given oxygen is often of the procedure
through a vein. given. is minimal.
Derived from The American Society of Anesthesiologists

of medications can help mitigate side emergency airway management, as
effects and avoid oversedation in this needed.2 While additional institutional
vulnerable population.11-14 and departmental requirements may
apply, ACEP states that “short courses”
CRITICAL DECISION such as Advanced Cardiac Life Support
What prerequisites, precautions, (ACLS) serve only as focused review and
and preparations are required are superseded by board certification.15
The minimum number of providers
for procedural sedation?
required to perform procedural sedation
Only properly credentialed emergency is two: the physician who performs the
physicians with privileges at their procedure and another trained clinician,
institution should perform procedural such as a nurse, who continuously
sedation. ACEP recommends that all
monitors the patient and vital signs.2
graduates of an emergency medicine
The patient should be informed in detail
residency program accredited by the
about the procedure and its potential
Accreditation Council for Graduate
risks, benefits, and complications.
Medical Education (ACGME) or the Verbal or written informed consent
American Osteopathic Association is acceptable, as long as institutional
(AOA) be credentialed on the basis of guidelines are followed.5,15 A history
their training.15 and physical should be completed,
The performing clinician is expected including an evaluation of comorbid
to be familiar with the medications conditions and allergies to medications.15
used, relevant reversal agents, side Specifically, the patient should be asked
effects, and complications. It is also about any previous exposure and
imperative for providers to have the response to analgesia or anesthesia.
capacity to rescue a patient from a Finally, an airway assessment should be
deeper level of sedation and provide performed, as previously discussed.
TABLE 2. LEMON Mnemonic Device
L Look externally Look for facial trauma, a beard, tongue size, and so on.
E Evaluate 3-3-2 rule 3-cm mouth opening; 3 finger breadths (chin to
hyoid bone); 2 finger breadths (hyoid bone to thyroid
cartilage).
M Mallampati Calculate the patient’s Mallampati score.
O Obstruction Look for swelling, vomit, and so on.
N Neck mobility Evaluate the range of neck motion.
Procedural sedation should be
administered in a spacious room
adequately stocked with equipment for
airway management and resuscitation.
Continuous heart rate and pulse
oximetry monitoring should be available,
along with interval blood pressure
measurements. In addition, oxygen,
suction, and airway adjuncts should be
immediately accessible. Reversal agents
relevant to the agents being used, such
as naloxone or flumazenil, should be
obtainable. Intravenous (IV) access
should be available, as it is needed
for most agents; however, the need
for access when using agents such as
ketamine is controversial.15,16
The ASA has provided detailed
guidelines about recommended
equipment for nonanesthesiologist-
performed sedation and anesthesia.4
All equipment should be checked, and
a time-out should be called, with all
involved staff present, immediately prior
to performing the sedation.
By monitoring end-tidal carbon
dioxide (ETCO2) continuously
throughout the procedure, clinicians can
reduce the risk of hypoxia and other
adverse respiratory events. It remains
unclear, however, whether continuous
capnography monitoring reduces more
serious complications.2 The need for
automatic supplementary oxygen
is debatable; a 2011 ACEP policy
statement recommends that its use be
left to the physician’s discretion.15

22 Critical Decisions in Emergency Medicine

 Ketamine, in particular, has been applies to emergency situations nor have been shown in animal models
shown to be safe without the use of emergency department procedural to be deleterious to the fetus, so the
supplemental oxygen.16 While some sedation. general recommendation is to provide
physicians argue that supplemental Physicians also debate the need routine supplemental oxygen during
oxygen can prevent hypoxia secondary for prophylactic antiemetics with the sedation of a pregnant patient.23
to hypoventilation, others counterargue procedural sedation. The ASA does Placing the patient in the left
that it can delay the recognition of not recommend the routine use of lateral recumbent position during
hypoxia and needed interventions.4,5,11,17 prophylactic antiemetics; however, its sedation is another simple precaution
guidelines indicate that patients should that can reduce medication-related
CRITICAL DECISION be fasting.19 While some agents used for hypotension by shifting the uterus off
Is fasting a prerequisite for procedural sedation (eg, propofol) have the vena cava. Another precaution
procedural sedation? antiemetic properties, ketamine stands is the administration of IV fluids.11
out as being emetogenic. Ketamine- In addition, pregnant patients have
Aspiration is a commonly cited
associated vomiting has been well higher rates of reflux esophagitis
risk of procedural sedation, although and heartburn, so prophylactic
studied in pediatrics, with reported
evidence of this complication in the metoclopramide or an H2 antagonist
rates as high as 28%. In one large
emergency department is sparse and is recommended to reduce the risk of
study, the use of prophylactic atropine
documented occurrences are rare. A vomiting and aspiration.11,23
and metoclopramide did not decrease
2016 meta-analysis found 1 case of this rate.20 Studies show conflicting Limited data are available on the
aspiration out of 2,370 sedations, data on the ability of ondansetron to safety of procedural medications in
an incidence rate of 1.2 per 1,000 reduce vomiting.21,22 Thus, the use of pregnancy, so most recommendations
sedations.18 ACEP’s Clinical Policy: prophylactic antiemetics with procedural are based on animal data. Ketamine is
Procedural Sedation and Analgesia in sedation in the emergency department is generally safe and has not been found
the Emergency Department states that best left to the clinician’s discretion. to be teratogenic; however, it increases
“Preprocedural fasting for any duration maternal heart rate and blood pressure
has not demonstrated a reduction in CRITICAL DECISION and should be avoided when managing
the risk of emesis or aspiration when a pregnant patient with hypertension.23
Which procedural sedation
administering procedural sedation Propofol is considered safe, but
medications are safe to use
and analgesia.”2 However, guidelines hypotension should be aggressively
for preprocedural fasting vary by with pregnant patients?
prevented and corrected. Furthermore,
organization and institution. Clinicians must be aware that neonatal depression is a concern when
Based on the current ASA guidelines, physiological changes during using these agents near the time of
many institutions continue to pregnancy increase certain risk factors delivery.23 Midazolam has a conflicting
recommend preprocedural fasting states during sedation. Decreased functional profile with possible teratogenicity and
of 2 hours for clear liquids and 6 hours residual capacity, increased oxygen should be avoided. Short-acting agents,
for a meal.19 As noted in ACEP’s policy, demand, increased respiratory rate, such as remifentanil and nitrous oxide,
the widely used ASA recommendations and relative hypotension are normal also can be considered.23
apply to elective general anesthesia in pregnancy and can be exacerbated
cases in which airway manipulation by procedural sedation agents. Both CRITICAL DECISION
is expected; neither recommendation maternal hypoxemia and hypercapnia How can the complications
of procedural sedation be
TABLE 3. Common Complications and First-Step Interventions managed?
Complication Interventions The major complications of
Agitation Calm patient; benzodiazepine procedural sedation are related to the
Apnea Oxygen and bag-valve-mask ventilation; evaluate the need for airway and apnea, although hypotension
intubation is common as well. A systematic review
Aspiration Suction; treat hypoxia with oxygen; evaluate for the need for and meta-analysis of 9,652 cases found
intubation and antibiotics that the most common adverse events
are hypoxia (40.2 per 1,000), vomiting
Bradycardia Usually self-resolving; atropine if persistent
(16.4 per 1,000), hypotension (15.2 per
Hypoxia Open airway; stimulate; oxygen
1,000), and apnea (12.4 per 1,000).18
Hypotension Usually self-resolving; fluid bolus or push-dose pressor if persistent Early recognition of a complication is
Laryngospasm High-flow oxygen; bag-valve-mask ventilation; consider paralytics crucial, which is why close monitoring is
and intubation a key component of the procedure. Once
Vomiting Suction; left lateral position; airway management identified, simple and rapid action can
correct most adverse effects (Table 3).

August 2018 n Volume 32 Number 8 23

 FIGURE 2. Mallampati Classification System
Class I
When performed properly, procedural
sedation in the emergency department is
safe: In the above cohort, no deaths, one
case of aspiration, and two unplanned
intubations were reported.
Hypoxia
Continuous pulse oximetry should
be performed on all patients to
immediately detect hypoxia. Many
providers also place all patients on
continuous oxygen during procedural
sedation; however, continuous oxygen
can mask early hypoxia and should be
performed judiciously. Capnography
monitoring can be used with pulse
oximetry to provide earlier detection
of hypoventilation and apnea, but it
has not been shown to reduce serious
events.2
Propofol and the combined use of
midazolam with an opiate result in
the highest rates of hypoxia.18 Once
recognized, this complication should
be immediately corrected with oxygen
and airway management techniques,
as required. A basic maneuver (eg,
head-tilt/chin-lift or jaw-thrust) is often
sufficient to correct hypoxia. However,
the physician should be prepared to
escalate interventions, as needed, with
positive pressure ventilation or advanced
airway management.
Vomiting
While the highest incidence of
vomiting occurs with ketamine, this
side effect can be triggered by any of
24 Critical Decisions in Emergency Medicine
Class II Class III
the medications used for sedation.18
Some providers opt to pretreat nausea
with antiemetics such as ondansetron;
however, studies conflict on the
effectiveness of this approach. Suction
should be immediately accessible
during sedation so that the airway can
be cleared without delay if vomiting
occurs. Vomiting patients should
receive an antiemetic agent, and airway
management should be escalated,
as needed. Sedation may need to be
aborted, depending on the severity of
vomiting; remember that vomiting can
continue even after reversal.
Hypotension
The clinical definition of hypotension
varies, and the significance of mild
hypotension during sedation is
unclear. Propofol and the combination
of midazolam with an opiate most
commonly precipitate a decrease in
blood pressure.18 Hypotension caused
by propofol is usually self-limiting due
to the short duration of action.24 Mild
elevations can be treated with an IV
fluid bolus (20 mL/kg) and by putting
the patient in the supine position. More
severe or persistent hypotension can
often be corrected with a push-dose
pressor such as phenylephrine.25
In rare cases, sedation may need to be
aborted if the patient’s hemodynamics
cannot tolerate the medication effects.
Avoiding hypotension should be a
consideration when deciding which
drug to use; the decision should be
Class IV
based on the patient’s previous reaction
history, comorbidities, and current
hemodynamics.
Apnea
Midazolam, alone or in combination
with an opiate, is the most likely sedative
to cause apnea; however, apnea can
occur with any sedative at sufficient
doses. Early recognition of apnea
can be achieved with capnography
monitoring and pulse oximetry. While
mild symptoms can usually be corrected
by stimulating the patient, apnea should
always be taken seriously; intermittent
apnea can be a warning sign of severe,
impending complications. Reversal
agents, such as naloxone or flumazenil,
can be used, as needed. Newer data show
that apnea is frequently preceded by
predictable alterations in ventilation
(eg, an ETCO2 that rises from <30 mm Hg
to >50 mm Hg).26 Apnea appears to
be a common yet easily correctible
complication: All apneic events in the
study were corrected with stimulation,
oxygen, or airway repositioning.26
Laryngospasm
Laryngospasm is a major concern with
the use of ketamine. Large meta-analyses
have shown a 0.3% incidence rate in
pediatric patients and a 0.4% incidence
rate in adults.18,27 High doses and pre-
existing upper respiratory infections in
children are thought to be risk factors,
but laryngospasm can occur at any
time. Providers must always be prepared
for the possibility.16 If identified, bag-
valve-mask ventilation is generally
sufficient, although the provider should
be prepared to paralyze and intubate,
if needed. Applying inward pressure
behind the lobule of the pinna of each
ear, while anteriorly dislocating the jaw,
at a location known as “Larson’s point”
or the “laryngospasm notch” may
terminate laryngospasm.28
Clinicians must be vigilant, both
during and after every sedation
procedure, to watch for warning signs
of adverse events that require rapid
intervention. The sedated patient should
be given special attention directly after
the procedure; when the procedure is
complete and the painful stimulus is
removed, medication-induced apnea
or hypotension previously masked
by sympathetic stimulation can
become more pronounced. To prevent
complications, emergency physicians
must choose the appropriate medications
for each patient in accordance with
the procedure, age, comorbidities,
and expected difficulty in airway
management.
CRITICAL DECISION
What are the indications,
contraindications, and doses
of drugs used for procedural
sedation?
No single recommended drug or drug
regimen exists for procedural sedation.
The process can require a sedative, an
analgesic, and/or a dissociative agent,
depending on the situation (Table 4).
Among the desirable drug qualities are
a rapid onset, a short duration, and
maintenance of hemodynamic stability —
all without causing major side effects.2
Ketamine
Ketamine is a dissociative agent
that provides analgesia and sedation,
while preserving the airway, breathing,
and blood pressure.16,29 It can be given
intravenously or intramuscularly (IM),
the latter being used commonly for
pediatric patients. The recommended
dose for ketamine is 1 mg/kg to 2 mg/kg
IV over 1 to 2 minutes for adults and
1.5 mg/kg to 2 mg/kg IV for pediatric
patients. Recommended IM dosing is
4 mg/kg to 5 mg/kg for both
populations. The typical duration of
action for the drug is 15 to 30 minutes
for IV delivery and 30 to 60 minutes
for IM delivery.16 Notably, IM delivery
produces higher rates of vomiting
and a longer recovery time, while IV
administration allows for repeat dosing,
as needed, to sustain the drug’s action.
Ketamine transiently increases heart
rate and blood pressure but does not
affect respiration unless rapidly injected.
Since rapid injection can cause transient
respiratory depression, ketamine should
be pushed slowly over 30 to 60 seconds
when given by IV.16,29 The agent also
has nondissociative analgesic properties
at lower doses (<0.3 mg/kg) and can be
used for both general pain management
and sedation.30
The most commonly reported side
effect of ketamine is an emergence
reaction (seen in 10%-20% of patients),
which can be managed with reassurance
in most cases or with benzodiazepines
in severe cases.29 Other adverse effects
include laryngospasm, vomiting, and
hypersalivation.29 Ketamine should not be
used for patients younger than 3 months
due to an increased risk of adverse airway
events, or for any patient with known or
suspected schizophrenia.16
Propofol
Propofol is a sedative-hypnotic agent
without analgesic properties. It has a
rapid onset of action (within 30-60
seconds) and a duration of action of
5 to 6 minutes.31 The benefits of the drug
include a rapid onset, short duration of
TABLE 4. Adult Procedural Sedation Agents
Medication Initial Dose
Ketamine 1 mg/kg
2-5 mg/kg
Propofol 0.5-1 mg/kg
Ketofol 1:1 mixture of 0.5 mg/kg ketamine
and 0.5 mg/kg propofol
Etomidate 0.15 mg/kg
Midazolam 0.05-0.1 mg/kg
0.1 mg/kg
0.2-0.5 mg/kg
0.5-0.75 mg/kg
Data from Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th ed.
action, and rapid recovery of cognitive
functions.5,31 Its other benefits include
antiemetic and euphoric effects. Since
propofol does not have analgesic
properties, appropriate analgesia should
be provided when using it for painful
procedures .32
Propofol in adults and children is
slowly injected, with an initial loading
dose of 1 mg/kg IV, followed by doses
of 0.5 mg/kg IV every 3 minutes, as
necessary until the appropriate level
of sedation is achieved.24 The agent is
contraindicated for patients allergic
to egg lecithin and soybeans.24 Major
side effects include hypotension and
respiratory depression, which usually
resolve quickly due to the short duration
of action. A short-acting, push-dose
pressor can be used if hypotension is
severe. Elderly patients often exhibit
hypotension, so initial dosing should
be reduced by 50%. A small amount of
lidocaine can be administered to prevent
pain at the injection site.24
Ketofol
Ketofol is a combination of ketamine
and propofol, coadministered in a
1:1 mixture, which has increased in
popularity in recent years. Theoretically,
this approach balances the negative
inotropic and respiratory effects of
propofol with the stimulant effects
of ketamine. Furthermore, propofol’s
antiemetic properties can balance
ketamine’s proemetic effects; propofol’s
sedative effects also can negate an
emergence reaction.2 Starting doses for
this regimen are 0.5 mg/kg of each agent.
Route Peak Effect Duration
IV 1-3 minutes 15-30 minutes
IM 5-20 minutes 30-60 minutes
IV 30-60 seconds 5-6 minutes
IV 30-60 seconds 15 minutes
IV 15-30 seconds 3-8 minutes
IV 2-3 minutes 20-30 minutes
IM 15-30 minutes 60-120 minutes
IN 10-15 minutes 45-60 minutes
PO 15-30 minutes 60-90 minutes
August 2018 n Volume 32 Number 8 25
 Alternative Agents
Ultrashort-acting opiates, such as
alfentanil and remifentanil, have been
used for procedural sedation in the
emergency department. Early reports
n Prepare all monitoring and airway management equipment prior to sedation, describe them as safe and effective, but
keeping it readily available during the procedure. added benefits remain unclear, when
n Consider the pros and cons of each medication and then tailor the sedation plan compared to established options.2
to the specific patient and context, accounting for the patient’s hemodynamic Nitrous oxide is an inhaled gas typically
status and the type of procedure.
composed of 30% oxygen and 30% to
n Simple maneuvers like stimulation, opening the airway, and providing oxygen can
70% nitrous oxide that provides rapid
correct most adverse apneic or hypoxic events.
anesthesia and recovery due to the low
n Ketamine and propofol are safe to use during pregnancy; however, midazolam
should be avoided.
solubility of nitrous oxide in the blood.
The agent has a rapid onset of less
The administration of ketofol for midazolam is 0.05 mg/kg IV or IM. than 1 minute and a recovery time
does not appear to provide a clinical When given by IV, onset occurs within 2 of 5 minutes. Self-administration
benefit over using either agent alone.33 to 3 minutes, with a duration of action is recommended for safe titration;
Specifically, the drug does not reduce of 20 to 30 minutes.31,38 While repeat cardiovascular side effects are minimal.
adverse respiratory events. Propofol, doses can be given in 3- to 5-minute However, sedation is often not complete
on the other hand, causes slightly more increments, as needed, physicians should for more painful procedures, and overall
hypotension when used alone, which is be cautious to avoid “dose stacking” use has been limited in emergency
of unclear clinical significance.34 from the residual effects of previous departments due to the need to use gas
doses. Midazolam is frequently used in scavenger systems.5,38
Etomidate pediatrics and can be given intranasally
Etomidate is a short-acting, sedative- (IN) at 0.2 mg/kg or orally (PO) at Summary
hypnotic agent that has minimal effects 0.5 mg/kg. While useful for children Procedural sedation is a safe
on respiratory and cardiovascular status. who fear needles, the IN route can cause practice in the emergency department
It can rapidly produce deep sedation irritation, and the PO route produces a that can reduce a patient’s anxiety
but has no analgesic properties; thus, an variable dosing response.5 or apprehension when undergoing a
analgesic should be provided for painful Midazolam can cause respiratory potentially painful procedure. Since
procedures. Adult dosing of etomidate for depression, bradycardia, and hypo­ the process is a core competency in
sedation is 0.1 mg/kg; onset occurs in less tension, particularly when combined
emergency medicine, providers must
than 1 minute, with a duration of action with an opiate.5,18 Paradoxical reactions,
understand the various medication
of 3 to 8 minutes. Repeat doses can be in which the patient becomes agitated,
options and how to balance the risks and
administered every 3 to 5 minutes, as occur in 1% to 15% of pediatric
needed.35,36 Myoclonus occurs in 20% to benefits of each drug to determine the
patients.5 Obese patients, the elderly,
40% of patients; while myoclonus is not and those with hepatic dysfunction safest and most effective sedation plan
dangerous to the patient, it can interfere can experience prolonged sedation.38 for each patient. Clinicians must also
with the procedure.2 Adrenal suppression Flumazenil can reverse the effects, but be prepared to manage patients as they
due to an etomidate-induced depression caution should be used for chronic transition between different sedation
of cortisol levels, particularly in septic benzodiazepine users, as flumazenil can depths and be skilled at anticipating,
or trauma patients, can occur; however, cause seizures in this population.31 detecting, and correcting complications.
several studies have shown no clinical
significance.2,37 Additional side effects
include respiratory suppression, nausea,
and vomiting.5,31,35

Midazolam
Midazolam is a benzodiazepine
with amnestic, hypnotic, and anxiolytic
properties, but no analgesic effect.38 It
is frequently used in conjunction with a
short-acting opiate like fentanyl. Of all
the benzodiazepines, midazolam has the
most rapid onset and strongest amnestic
effects.38 The traditional starting dose
n Failing to prepare for hemodynamic and airway complications.
n Disregarding the increased risk of hypotension and apnea when using
combinations like propofol and an opiate, or a benzodiazepine and an opiate.
n Overlooking the major risk factors and contraindications of various medications.
n Neglecting the patient immediately following the procedure, while the patient is
still sedated.

26 Critical Decisions in Emergency Medicine

 CASE RESOLUTIONS
■ CASE ONE
The young man with a dislocated
shoulder required procedural sedation
to facilitate reduction. A detailed
history was gathered, with a special
focus on his medical history and details
about medication use, allergies, and
fasting status. The patient’s airway
was assessed for any signs of difficulty,
using the LEMON mnemonic device.
The patient consented to the procedure
after the risks, benefits, and possible
complications were explained.
The sedation plan was coordinated
with the nurse; monitoring equipment,
including pulse oximetry and
capnography, were available. An
airway and code cart were nearby, and
oxygen and suction were checked. A
time-out was called immediately prior
to administering the medications.
After the procedure, the nurse closely
observed the patient until he fully
regained consciousness and could
follow verbal commands.
Since most adverse events occur
within 30 minutes after sedation, he
was observed for at least 30 minutes
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prior to discharge.24,39 The patient
was given written instructions that
explained the potential medication-
specific side effects and solutions, as
well as clear directions on when to
return to the emergency department.16
■ CASE TWO
Propofol had several benefits for
the elderly man with a dislocated hip
and an extensive medical history,
including a rapid onset of action
and short duration. Fentanyl was
appropriately coadministered for
its analgesic effects. The downside
of using propofol in this situation
was its negative inotropic effect.
Although hypotension and respiratory
depression frequently occur with
propofol alone, they are exacerbated
when propofol is combined with an
opioid analgesic.
The patient’s blood pressure
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reduced hip. In retrospect, the provider
should have considered a reduced dose
of propofol or the use of alternative
agents, such as ketamine or etomidate,
that are more hemodynamically neutral.
■ CASE THREE
The young, pregnant woman with a
dislocated ankle required sedation and
analgesia for reduction. The emergency
physician considered the physiological
changes that occur during pregnancy,
especially the added compression of
the inferior vena cava, higher risk of
aspiration, and hypoxia secondary to
reduced functional residual capacity.
Midazolam was not used because
it is categorized as a pregnancy
class D drug due to its potential
teratogenicity. Instead, the physician
used propofol because it is generally
considered safe, and then monitored
the patient for hypotension. Routine
supplemental oxygen was provided, the
patient was placed in the left lateral
recumbent position, and IV fluids were
administered during the procedure.
Prophylactic metoclopramide was also
given.
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35(2):168-173.
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RJ, Monuteaux MC. Characteristics of and
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during procedural sedation. Ann Emerg Med. 2016
Nov;68(5):564-573.
27. Green SM, Roback MG, Krauss B, et al. Predictors
of airway and respiratory adverse events with
ketamine sedation in the emergency department:
August 2018 n Volume 32 Number 8 27
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children. Ann Emerg Med. 2009 Aug;54(2):158-168.
28. Larson CP Jr. Laryngospasm—the best treatment.
Anesthesiology. 1998 Nov;89(5):1293-1294.
29. Strayer RJ, Nelson LS. Adverse events associated
with ketamine for procedural sedation in adults.
Am J Emerg Med. 2008 Nov;26(9):985-1028.
30. Lee EN, Lee JH. The effects of low-dose ketamine
on acute pain in an emergency setting: a systematic
review and meta-analysis. PLoS One. 2016 Oct 27;
11(10):e0165461.
31. Hansen TG. Sedative medication outside the
operating room and the pharmacology of sedatives.
Curr Opin Anesthesiol. 2015 Aug;28(4):446-452.
32. Burbulys DB. Procedural sedation and analgesia.
In: Marx JA, Hockberger RS, Walls RM, et al, eds.
Rosen’s Emergency Medicine: Concepts and Clinical
Practice, vol. 1. 8th ed. Philadelphia, PA: Saunders;
2014:50-60.
33. David H, Shipp J. A randomized controlled trial
of ketamine/propofol versus propofol alone for
emergency department procedural sedation. Ann
Emerg Med. 2011 May;57(5):435-441.
34. Ferguson I, Bell A, Treston G, New L, Ding
M, Holdgate A. Propofol or ketofol for procedural
sedation and analgesia in emergency medicine—the
POKER study: a randomized double-blind clinical
trial. Ann Emerg Med. 2016 Nov;68(5):574-582.
35. Miner JR, Danahy M, Moch A, Biros M. Randomized
clinical trial of etomidate versus propofol for
procedural sedation in the emergency department.
Ann Emerg Med. 2007 Jan;49(1):15-22.
36. Brown TB, Lovato LM, Parker D. Procedural sedation
in the acute care setting. Am Fam Physician. 2005
Jan 1;71(1):85-90.
37. Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single
induction dose of etomidate versus other induction
agents for endotracheal intubation in critically ill
patients. Cochrane Database Syst Rev. 2015 Jan 8;1:
CD010225.
38. Bahn EL, Holt KR. Procedural sedation and analgesia:
a review and new concepts. Emerg Med Clin North
Am. 2005 May;23(2):503-517.
39. Newman DH, Azer MM, Pitetti RD, Singh S. When is a
patient safe for discharge after procedural sedation?
The timing of adverse effect events in 1,367 pediatric
procedural sedations. Ann Emerg Med. 2003 Nov;
42(5):627-635.

28 Critical Decisions in Emergency Medicine

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August 2018 n Volume 32 Number 8 29
 CME
Reviewed by Lynn Roppolo, MD, FACEP

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 1
Credits™, and 5 AOA Category 2-B credits for completing this activity in its

QUESTIONS entirety. Submit your answers online at acep.org/cdem; a score of 75% or better
is required. You may receive credit for completing the CME activity any time within
3 years of its publication date. Answers to this month’s questions will be published
in next month’s issue.

1 An individual who visited a clinic prior to travel is likely

to experience which of the following? 6 A 45-year-old health care worker who returns from
working in Sierra Leone in West Africa presents
with a fever of 38.6°C (101.5°F), abdominal pain,
A. Fever
B. Malaria and diarrhea. His physical examination is significant
C. Self-limited illness for a purpuric rash. What is the most appropriate
D. Severe disease next step?
A. Administer IV fluid bolus therapy

2 Acute hemorrhagic fever syndrome includes a fever

of what duration?
B.
C.
Contact the local health department
Place him in isolation
A. >1 month D. Place him on a cardiac monitor
B. <1 month
C.
D.
<1 week
<3 weeks 7 A 50-year-old man presents with fever and
pneumonia after a recent trip to the Arabian
peninsula, where he volunteered at a local health

3 By what route is Ebola transmitted?

A. An insect bite
clinic. Which of the following pathologies should
be suspected?
B. Contaminated food A. Cryptococcal meningitis
C. Contaminated water B. Japanese encephalitis
D. Direct contact with infected bodily fluids C. MERS-CoV
D. Q fever

4 A 35-year-old man who recently returned from a trip

8
to East Africa presents with fever and generalized Which condition is correctly paired with its usual
malaise. Other than a temperature of 38.3°C (100.9°F), incubation period?
his vital signs are normal. His physical examination is A. Chikungunya — 3 weeks
unremarkable, CBC shows leukocytosis of 14,000 B. Hepatitis E — 1 week
cells/mm3, a basic metabolic panel is unremarkable, and C. Malaria — <10 days to months
no Plasmodium is visualized on peripheral blood smears. D. SARS — 2 weeks
What is the most appropriate next step?
A. Continue symptomatic care and repeat blood smears
for 12 to 24 hours 9 When a specific etiological diagnosis can be made,
what is the most frequently identified cause of
fever in the returned traveler?
B. Inform the patient that he does not have malaria and
discharge home A. Dengue fever
C. Start intravenous treatment with an artemisinin-based B. Ebola virus disease
compound therapy C. Enteric fever
D. Start outpatient chloroquine D. Malaria

5 Travelers from which geographic area are at the

highest risk of acquiring enteric fever?
10 Which disease is correctly paired with its typical
mode of transmission?
A. South America A. Chikungunya — contaminated food or water
B. South Asia B. Ebola virus disease — deer tick
C. Sub-Saharan Africa C. Enteric fever — Anopheles mosquito
D. Western Europe D. Zika — Aedes aegypti mosquito

30 Critical Decisions in Emergency Medicine

11 A 5-year-old boy presents after falling off his bike.
He is alert and oriented and has a 5-cm laceration
16
on his chin that requires stitches. He is anxious and
crying inconsolably. What medication(s) can be given
IM for stitching under procedural sedation?
A 20-year-old woman is under procedural sedation
for a dental procedure. A few minutes into the
procedure she starts shouting that there are bugs
all over the ceiling. Which medication can cause
this phenomenon?

A. Etomidate A. Etomidate
B. Fentanyl
B. Ketamine
C. Ketamine
C. Midazolam and morphine
D. Midazolam
D. Propofol

12 Under what thyroid cartilage–to-mandible distance
would you anticipate a difficult intubation?

17 What is the most common side effect of
etomidate?
A. Hypotension
A. 2 finger breadths B. Myoclonus
B. 3 finger breadths C. Nausea and vomiting
C. 4 finger breadths D. Tachycardia
D. 5 finger breadths

13 A young woman presents with a dislocated ankle
that requires reduction. She has no medical

18 Which of the following medications can be
administered alone, without an analgesic agent,
for procedural sedation?
history and takes no medications except for oral A. Etomidate
contraceptives. She is allergic to peanuts and eggs. B. Ketamine
Acetaminophen and ibuprofen have partially reduced C. Midazolam
the pain. Which medication is contraindicated for D. Propofol
procedural sedation?
A. Etomidate
B. Midazolam

19
According to ACEP’s clinical policy, how long
should a patient fast before undergoing
procedural sedation?
C. Morphine A. 2 hours for liquids only
D. Propofol B. 2 hours for liquids and 6 hours for solids
C. 6 hours for solids only

14 A 65-year-old man requires procedural sedation for
a shoulder relocation. He is diabetic and has COPD.
D. No fasting is required

Which medication would be most likely to induce

hypotension?
20 Which medication should be avoided during
procedural sedation to relocate the shoulder of
a 25-year-old woman who is 34 weeks pregnant?
A. Etomidate
B. Ketamine A. Flumazenil
B. Ketamine
C. Morphine
C. Midazolam
D. Propofol
D. Propofol

15
Which side effect is more common with IM
ketamine?
A. Agitation
B. Apnea
C. Hypotension
D. Vomiting

ANSWER KEY FOR JULY 2018, VOLUME 32, NUMBER 7

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
D D D B A A D D A B A D A D C D D D B A

August 2018 n Volume 32 Number 8 31

 Drug Box
ANDEXANET ALFA
By Paris Cook, PharmD; and Aimee Mishler, PharmD, BCPS,
Maricopa Medical Center, Phoenix, AZ
Andexanet alfa was recently approved by the FDA for the treatment of
life-threatening or uncontrolled bleeding caused by the anticoagulants
rivaroxaban and apixaban. It is the first agent approved for the reversal
of these two factor Xa inhibitors. Andexanet alfa is available at limited
sites throughout the US; wider distribution is expected in early 2019.
Mechanism of Action
The antidote binds to and sequesters the factor Xa inhibitors. In
addition, it inhibits the activity of tissue factor pathway inhibitor
(TFPI), increasing tissue factor-initiated thrombin generation.
Dosing
If the last dose of medication was taken >8 hours ago, use low dose.
If the last dose of medication was taken <8 hours ago or unknown,
the dose should be based on the amount of factor Xa taken.
Apixaban: Last dose ≤5 mg, use low dose; last dose >5 mg
or unknown, use high dose.
Rivaroxaban: Last dose ≤10 mg, use low dose; last dose
>10 mg or unknown, use high dose.
Low Dose: 400-mg IV bolus administered at a rate of
~30 mg/minute, followed 2 minutes later by 4 mg/minute IV
infusion for up to 120 minutes
High Dose: 800-mg IV bolus administered at a rate of
~30 mg/minute, followed 2 minutes later by 8 mg/minute IV
infusion for up to 120 minutes
Adverse Reactions
The most common side effect is a local infusion site reaction
(≥10%), followed by deep vein thrombosis (6%), ischemic stroke
(5%), urinary tract infections, and pneumonia (both occurring
in ≥5% of patients).
FDA Black Box Warning: Treatment with andexanet alfa has been
associated with life-threatening complications, including arterial
and venous thromboembolic events, ischemic events (including
myocardial infarction and ischemic stroke), cardiac arrest, and
sudden deaths. Monitor for thromboembolic events and initiate
anticoagulation when medically appropriate. Monitor for signs
and symptoms that precede cardiac arrest and provide treatment
as needed.
Tox Box
QUETIAPINE OVERDOSE
By Jenna Otter, MD; and Christian A. Tomaszewski, MD, MS,
MBA, FACEP, University of California, San Diego
Quetiapine is a second-generation antipsychotic available
in immediate- and extended-release formulations. It is FDA
approved for schizophrenia, bipolar disorder, and as adjunct
treatment for major depressive disorder.
Pharmacokinetics
• Lipophilic with a large volume of distribution (not dialyzable)
• Levels peak after 2-3 hours, with a half-life of 6 hours.
• In overdose, antimuscarinic effects can delay absorption.
• Metabolized by CYP3A4
Mechanism of Action
• Weak antagonism at D2, M1, 5HT1A receptors = sedation
• Potent antagonism at a1 adrenergic receptors =
hypotension
• Some blockade at fast sodium channels = QRS widening
• Can affect delayed rectifier current = QT prolongation
Clinical Presentation
• Tachycardia from antimuscarinic effects
• Hypotension from peripheral a1 blockade
• Miosis with depressed mental status (opioid mimic)
• Rarely associated with neuroleptic malignant syndrome
(NMS)
Diagnostic Evaluation
• ECG nonspecific: tachycardia with prolonged QTc
• Lab testing: nonspecific (may be false positive for TCA)
• Evaluate for coingestants (eg, acetaminophen)
Management and Disposition
• Consider activated charcoal in alert patients who present
<1-2 hours after a large overdose, especially with extended
release formulations.
• Intubate, if necessary (rare with quetiapine).
• Treat hypotension with IV fluids; if persistent, add
norepinephrine or phenylephrine.
• In cases of refractory shock, consider intralipid, given its
lipophilicity.
• Treat NMS with benzodiazepines and cooling.
• An asymptomatic patient with a normal ECG 6 hours after
an overdose requires no further cardiac monitoring.