Anaphylaxis in Pediatric Patients: June 2019

Volume 16, Number 6

Early Recognition and Treatment Authors

Jeranil Nunez, MD

Are Critical for Best Outcomes Site Director, Pediatric Emergency Medicine Education, Mount Sinai
Beth Israel; Senior Faculty, Department of Emergency Medicine,
Icahn School of Medicine at Mount Sinai, New York, NY
Genevieve Santillanes, MD, FAAP, FACEP
Abstract Associate Professor of Clinical Emergency Medicine, LAC+USC
Medical Center, Keck School of Medicine of USC, Los Angeles, CA

Anaphylaxis is a time-sensitive, clinical diagnosis that is often Peer Reviewers

misdiagnosed because the presenting signs and symptoms are Bharati Beatrix Bansal, MD
similar to those of other disease processes. This issue reviews the Assistant Professor of Pediatrics, Division of Pediatrics, Division of
Emergency Medicine, University of Texas Southwestern Medical
criteria for diagnosing a pediatric patient with anaphylaxis and Center/Children's Medical Center, Dallas, TX
offers evidence-based recommendations for first- and second-line Ronna Campbell, MD, PhD
treatment, including the use of epinephrine, antihistamines, and Associate Professor of Emergency Medicine, Department of
Emergency Medicine, Mayo Clinic, Rochester, MN
corticosteroids. Guidance is also provided for the appropriate
disposition of patients with anaphylaxis, including prescribing Prior to beginning this activity, see “CME Information”
on the back page.
epinephrine autoinjectors and offering training on how to use
them, educating patients and families on avoidance of known This issue is eligible for 2 Pharmacology CME credits.

offending allergens, and referring the patient to a specialist in

allergy and immunology.

Editors-in-Chief
Ilene Claudius, MD
Associate Professor; Director,
Process & Quality Improvement
Program, Harbor-UCLA Medical
Center, Torrance, CA
Tim Horeczko, MD, MSCR, FACEP,
FAAP
Associate Professor of Clinical
Emergency Medicine, David Geffen
School of Medicine, UCLA; Core
Faculty and Senior Physician, Los
Angeles County-Harbor-UCLA
Medical Center, Torrance, CA
Editorial Board
Jeffrey R. Avner, MD, FAAP Medicine, Los Angeles, CA
Chairman, Department of
Pediatrics, Professor of Clinical
Pediatrics, Maimonides Children's
Hospital of Brooklyn, Brooklyn, NY
Steven Bin, MD
Associate Clinical Professor, UCSF
School of Medicine; Medical Director,
Pediatric Emergency Medicine, UCSF
Benioff Children's Hospital, San
Francisco, CA
Richard M. Cantor, MD, FAAP, FACEP
Professor of Emergency Medicine
and Pediatrics; Section Chief,
Pediatric Emergency Medicine;
Medical Director, Upstate Poison
Control Center, Golisano Children's
Hospital, Syracuse, NY
Steven Choi, MD, FAAP
Chief Quality Officer and Associate
Dean for Clinical Quality, Yale
Medicine/Yale School of Medicine;
Vice President, Chief Quality Officer, Assistant Professor of Emergency
Yale New Haven Health System,
New Haven, CT
Ari Cohen, MD, FAAP
Chief of Pediatric Emergency
Medicine, Massachusetts General
Hospital; Instructor in Pediatrics,
Harvard Medical School, Boston, MA
Jay D. Fisher, MD, FAAP, FACEP
Clinical Professor of Emergency
Medicine and Pediatrics, University
of Nevada, Las Vegas School of
Medicine, Las Vegas, NV
Marianne Gausche-Hill, MD, FACEP,
FAAP, FAEMS
Medical Director, Los Angeles
County EMS Agency; Professor of
Clinical Emergency Medicine and
Pediatrics, David Geffen School
of Medicine at UCLA; Clinical
Faculty, Harbor-UCLA Medical
Center, Department of Emergency
Michael J. Gerardi, MD, FAAP,
FACEP, President
Associate Professor of Emergency
Medicine, Icahn School of Medicine
at Mount Sinai; Director, Pediatric
Emergency Medicine, Goryeb
Children's Hospital, Morristown
Medical Center, Morristown, NJ
Sandip Godambe, MD, PhD
Chief Quality and Patient Safety Officer,
Professor of Pediatrics, Attending
Physician of Emergency Medicine,
Children's Hospital of The King's
Daughters Health System, Norfolk, VA
Ran D. Goldman, MD
Professor, Department of Pediatrics,
University of British Columbia;
Research Director, Pediatric
Emergency Medicine, BC Children's
Hospital, Vancouver, BC, Canada
Joseph Habboushe, MD, MBA
Medicine, NYU/Langone and
Bellevue Medical Centers, New
York, NY; CEO, MD Aware LLC
Alson S. Inaba, MD, FAAP
Pediatric Emergency Medicine
Specialist, Kapiolani Medical Center
for Women & Children; Associate
Professor of Pediatrics, University
of Hawaii John A. Burns School of
Joshua Nagler, MD, MHPEd
Medicine, Honolulu, HI
Madeline Matar Joseph, MD, FACEP,
FAAP Medical School; Associate Division
Professor of Emergency Medicine
and Pediatrics, Assistant Chair,
Pediatric Emergency Medicine
Quality Improvement, Pediatric
James Naprawa, MD
Emergency Medicine Division,
University of Florida College of
Medicine-Jacksonville,
Jacksonville, FL
Joshua Rocker, MD
Stephanie Kennebeck, MD
Associate Pr ofessor, University of
Cincinnati Department of Pediatrics,
Cincinnati, OH
Anupam Kharbanda, MD, MS
Chief, Critical Care Services
Steven Rogers, MD
Children's Hospitals and Clinics of
Minnesota, Minneapolis, MN
Tommy Y. Kim, MD, FAAP, FACEP
Associate Professor of Pediatric
Emergency Medicine, University of
California Riverside School of Medicine,
Riverside Community Hospital,
Department of Emergency Medicine,
Riverside, CA
Melissa Langhan, MD, MHS
Associate Professor of Pediatrics and
Emergency Medicine; Fellowship
Director, Director of Education,
Pediatric Emergency Medicine, Yale
University School of Medicine, New
Haven, CT
Robert Luten, MD
Professor, Pediatrics and
Emergency Medicine, University of
Florida, Jacksonville, FL
Garth Meckler, MD, MSHS
Associate Professor of Pediatrics,
University of British Columbia;
Division Head, Pediatric Emergency
Medicine, BC Children's Hospital,
Vancouver, BC, Canada
Assistant Professor of Pediatrics
and Emergency Medicine, Harvard
Chief and Fellowship Director, Division
of Emergency Medicine, Boston
Children’s Hospital, Boston, MA
Attending Physician, Emergency
Department USCF Benioff
Children's Hospital, Oakland, CA
Associate Chief and Medical
Director, Assistant Professor of
Pediatrics and Emergency Medicine,
Cohen Children's Medical Center of
New York, New Hyde Park, NY
Associate Professor, University of
Connecticut School of Medicine,
Attending Emergency Medicine
Physician, Connecticut Children's
Medical Center, Hartford, CT
Christopher Strother, MD
Associate Professor, Emergency
Medicine, Pediatrics, and Medical
Education; Director, Pediatric
Emergency Medicine; Director,
Simulation; Icahn School of Medicine
at Mount Sinai, New York, NY
Adam E. Vella, MD, FAAP
Director of Quality Assurance,
Pediatric Emergency Medicine,
New York-Presbyterian,
Weill Cornell, New York, NY
David M. Walker, MD, FACEP, FAAP
Chief, Pediatric Emergency
Medicine, Department of Pediatrics,
Joseph M. Sanzari Children's
Hospital, Hackensack University
Medical Center, Hackensack, NJ
Vincent J. Wang, MD, MHA
Professor of Pediatrics and
Emergency Medicine; Division
Chief, Pediatric Emergency
Medicine, UT Southwestern
Medical Center; Director of
Emergency Services, Children's
Health, Dallas, TX
International Editor
Lara Zibners, MD, FAAP, FACEP,
MMed
Honorary Consultant, Paediatric
Emergency Medicine, St. Mary's
Hospital Imperial College Trust,
London, UK; Nonclinical Instructor
of Emergency Medicine, Icahn
School of Medicine at Mount Sinai,
New York, NY
Pharmacology Editor
Aimee Mishler, PharmD, BCPS
Emergency Medicine Pharmacist,
Program Director – PGY2
Emergency Medicine Pharmacy
Residency, Maricopa Medical
Center, Phoenix, AZ
CME Editor
Brian S. Skrainka, MD, FACEP, FAAP
Clinical Assistant Professor of
Emergency Medicine, Oklahoma
State University Center for Health
Sciences, The Children’s Hospital at
Saint Francis, Tulsa, OK
APP Liaison
Brittany M. Newberry, PhD, MSN,
MPH, APRN, ENP-BC, FNP-BC
Faculty, Emory University School
of Nursing, Emergency Nurse
Practitioner Program, Atlanta, GA;
Nurse Practitioner, Fannin Regional
Hospital Emergency Department,
Blue Ridge, GA
Case Presentations
A 3-year-old girl with a known peanut allergy arrives to
your ED via EMS. The girl was given a cookie by a class-
mate and immediately developed a generalized urticarial
rash. EMS personnel gave her 12.5 mg of oral diphen-
hydramine and transported her to the ED. On examina-
tion, the patient has a heart rate of 160 beats/min with
normal oxygenation and perfusion. She has bilateral peri-
orbital swelling, without respiratory distress, wheezing,
vomiting, or diarrhea. The accompanying daycare teacher
tells you that the girl has previously been admitted to the
intensive care unit for anaphylaxis. You call the girl's
parents for more information and wonder what to do in
the meantime. Is diphenhydramine sufficient treatment
for this patient? Are corticosteroids indicated? Is this just
an allergic reaction or could it be an anaphylactic reac-
tion? What are the criteria for diagnosis of anaphylaxis?
What are the indications for administering epinephrine in
patients with anaphylaxis?
Your next patient is an 8-year-old boy with a history
of moderate persistent asthma. He presented to the ED via
EMS for respiratory distress and wheezing. The patient
was walking home from school when he began coughing
and felt short of breath. When he arrived home, he was
coughing persistently, wheezing, diaphoretic, and red in
the face. On arrival to the ED, the patient is given inhaled
nebulized albuterol via face mask and is afebrile with the
following vital signs: oxygen saturation, 90% on oxygen;
heart rate, 150 beats/min; respiratory rate, 38 breaths/min;
and blood pressure, 135/80 mm Hg. He appears tired, has
moderate retractions with poor aeration on lung examina-
tion, bounding pulses, and his skin appears diffusely red
and warm. He states he has an egg allergy. He previously
had a remote admission for an asthma exacerbation but has
not had any surgeries. He had been in good health prior to
today. You are concerned that this could be an anaphylac-
tic reaction. What is the best treatment for anaphylaxis?
How long should you observe the patient for a biphasic
reaction or fatal anaphylaxis?
An otherwise healthy 15-year-old boy is brought to
the ED by EMS for a syncopal episode at home. In the
past 4 hours, he has had 4 episodes of nonbilious vomiting
and 3 episodes of watery, nonbloody diarrhea with crampy
abdominal pain. He has not had a fever. The boy’s parents
state that he was going to use the restroom after eating
dinner, and he fell on his way to the bathroom. EMS
administered a 20-mL/kg bolus of normal saline en route
to the ED. On arrival to the ED, the patient appears tired
and is diaphoretic. His vital signs are as follows: oxygen
saturation, 99% on room air; heart rate, 150 beats/min;
respiratory rate, 22 breaths/min; blood pressure, 60/40
mm Hg, and temperature, normal. He is able to answer
questions, has clear lungs, no abdominal tenderness, and
a capillary refill time of 3 to 4 seconds. The boy appears
to have normal sinus rhythm on the monitor. His bedside
glucose level is 110 mg/dL. The parents deny sick contacts
or recent travel history. The patient has no known aller-
Copyright © 2019 EB Medicine. All rights reserved. 2
gies and is not taking any medications. His vital signs
do not improve after a second 20-mL/kg bolus of normal
saline. You consider his diagnosis. Is this dehydration
from acute gastroenteritis or food poisoning, or perhaps
an atypical presentation of anaphylaxis? Are there any
labs that can help you decide if this is an anaphylactic
reaction? You recall that patients with anaphylaxis can
present with gastrointestinal and cardiovascular symp-
toms, with no skin changes. You decide to administer 0.3
mg of epinephrine IM. The boy's mental status and capil-
lary refill time improve, but he is persistently hypotensive.
Should you administer another dose of epinephrine? What
are the criteria for admission of a patient with anaphy-
laxis?
Introduction
An allergic reaction is an overreaction of the im-
mune system to a foreign substance (allergen). Ana-
phylaxis is a type of an allergic reaction that is an
acute, severe systemic hypersensitivity reaction that
can rapidly lead to death.1 The signs and symptoms
of anaphylaxis are similar to other common illness-
es, which can make diagnosis challenging. Atypical
anaphylaxis can be even more difficult to diagnose,
because some of the typical signs of anaphylaxis are
not present. As such, many cases are misdiagnosed
and undertreated.2-7 Early treatment of anaphy-
laxis with epinephrine can prevent progression
to life-threatening respiratory failure and/or car-
diovascular collapse.1,8-15 All published guidelines
recommend early administration of epinephrine for
anaphylaxis, even in uncertain cases.1,11-18 Despite
this recommendation, studies suggest that epineph-
rine remains underutilized by emergency clinicians,
and that gaps in knowledge of management of
anaphylaxis exist among primary care providers as
well.19,20 Furthermore, patients with anaphylaxis
are often misdiagnosed with an “allergic reaction”
and given antihistamines and corticosteroids instead
of epinephrine.2,5,7 Recent studies suggest that the
incidence of anaphylaxis is increasing globally,21-26
with an increase in both emergency department
(ED) visits and hospitalizations. Pediatricians, first
responders, and emergency clinicians should there-
fore be well versed in the variety of presentations of
anaphylaxis and remain vigilant.
This issue of Pediatric Emergency Medicine Practice
offers guidance on the identification of patients with
anaphylaxis, including those with atypical presenta-
tions, reviews recent guidelines and evidence-based
recommendations for first-line and second-line ana-
phylaxis treatment, describes risk factors associated
with biphasic anaphylaxis and fatal anaphylaxis, and
discusses guidelines for patient disposition.
Reprints: www.ebmedicine.net/pempissues
Critical Appraisal of the Literature
A literature review was performed using the
PubMed and Ovid MEDLINE® databases with the
search terms anaphylaxis, allergic reaction, food allergy,
drug allergy, anaphylactic shock, epinephrine, adrenaline,
antihistamines, glucocorticoids, biphasic reaction, and
fatal anaphylaxis. Additionally, the references of each
identified article were reviewed for relevant cita-
tions. A total of 143 articles from 1985 to the present
were chosen for inclusion.
National and international organizations have
published guidelines for the diagnosis, manage-
ment, and treatment of anaphylaxis.1,8-15 (See Table
1.) In 2011, the World Allergy Organization released
anaphylaxis guidelines that have since been updated
with current evidence-based recommendations. In
2014, both the International Consensus and the Joint
Task Force on Practice Parameters released updated
anaphylaxis guidelines and practice parameters. A
search of the National Guideline Clearinghouse also
yielded a 2014 anaphylaxis guideline from the Euro-
pean Academy of Allergy and Clinical Immunology.
Although there are multiple published guide-
lines on the recognition and treatment of anaphylax-
is, no large randomized controlled trials have been
conducted. There are no randomized, placebo-con-
trolled studies of medications used for the treatment
of anaphylaxis in adults or children. A search of the
Table 1. Relevant Guidelines for the Assessment and Management of Anaphylaxis
Year Organization
2006 Symposium convened by the National Institute of Allergy and Infectious
Disease/Food Allergy and Anaphylaxis Network (13 participating
organizations, including the American College of Emergency
Physicians and the American Academy of Pediatrics)
2011 World Allergy Organization (WAO)
2012
2013
2015
2014 European Academy of Allergy and Clinical Immunology (EAACI)
Taskforce
2014 International Collaboration in Asthma, Allergy and Immunology
(iCAALL), the World Allergy Organization, the American Academy
of Allergy, Asthma & Immunology (AAAAI), the American College of
Allergy, Asthma & Immunology (ACAAI), and the European Academy
of Allergy and Clinical Immunology
2014 Joint Task Force on Practice Parameters, representing the American
Academy of Allergy, Asthma & Immunology; the American College
of Allergy, Asthma & Immunology; and the Joint Council of Allergy,
2015 Asthma and Immunology (JCAAI)
June 2019 • www.ebmedicine.net 3 Copyright © 2019 EB Medicine. All rights reserved.
Cochrane Database of Systematic Reviews yielded
several systematic reviews on anaphylaxis treatment
and management: a 2007 review of H1 antihista-
mines in anaphylaxis,27 a 2009 review of epineph-
rine,28 a 2012 review of epinephrine autoinjectors,29
and a 2012 review of glucocorticoids.30
The literature on pediatric anaphylaxis is
limited, and it is mostly extrapolated from adult
studies, retrospective chart reviews, epidemiologic
studies, review articles, and case reports. Most stud-
ies are retrospective, with associated limitations.
Results are difficult to compare because there was
no standard definition for anaphylaxis until publi-
cation of consensus guidelines in 2006.1 (See Table
2, page 4.) Reported incidence and outcomes vary
greatly, likely due to the lack of a standard definition
and variability in reporting. When available, studies
restricted to pediatric patients were reviewed and
included. However, most studies on anaphylaxis
include all ages, so pediatric-specific data are not
always available, and many of the references in this
review involve combined pediatric and adult data.
Relevant adult-only studies were included when
necessary to supplement limited pediatric data.
Title
Second symposium on the definition and management of
anaphylaxis: summary report—second National Institute of
Allergy and Infectious Disease/Food Allergy and Anaphylaxis
Network Symposium1
World Allergy Organization guidelines for the assessment and
management of anaphylaxis8
2012 update9
2013 update of the evidence base10
2015 update of the evidence base11
Anaphylaxis: guidelines from the European Academy of Allergy
and Clinical Immunology12
International Consensus (ICON) document on anaphylaxis13
Emergency department diagnosis and treatment of anaphylaxis:
a practice parameter15
Anaphylaxis—a practice parameter update 201514
www.ebmedicine.net
 Epidemiology
The incidence of anaphylaxis is unclear due to vari-
ability in clinical presentation, recognition, report-
ing, etiology, diagnostic coding, study populations,
study designs, geographic variations, and data
sources. Studies based on self-reports or ED data
may focus on severe reactions, underestimating the
true incidence of anaphylaxis. In several studies,
approximately one-third to half of patients meeting
criteria for food-related anaphylaxis did not receive a
discharge diagnosis of anaphylaxis.2,3,31
In a 2014 survey of adults living in the United
States, 1.6% to 5.1% of respondents self-reported a
history of at least 1 lifetime episode of anaphylaxis.32
A comprehensive literature review by the American
Table 2. Clinical Criteria For Diagnosing
Anaphylaxis
Anaphylaxis is highly likely when any one of the following 3
criteria are fulfilled:
1. Acute onset of an illness (minutes to several hours) with
involvement of the skin, mucosal tissue, or both (eg,
generalized hives, pruritus or flushing, swollen lips-tongue-
uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-
bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ
dysfunction (eg, hypotonia [collapse], syncope,
incontinence)
2. Two or more of the following that occur rapidly after exposure to
a likely allergen for that patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized
hives, itch-flush, swollen lips-tongue-uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-
bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia
[collapse], syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy
abdominal pain, vomiting)
3. Reduced BP after exposure to known allergen for that patient
(minutes to several hours):
a. Infants and children: low systolic BP (age specific) or
greater than 30% decrease in systolic BP*
b. Adults: systolic BP of less than 90 mm Hg or greater than
30% decrease from that person’s baseline
Abbreviations: BP, blood pressure; PEF, peak expiratory flow.
*Low systolic blood pressure for children is defined as < 70 mm Hg for
patients aged 1 month to 1 year, < (70 mm Hg + [2 x age]) for patients
aged 1 to 10 years, and < 90 mm Hg for patients aged 11 to 17 years.
Reprinted from the Journal of Allergy and Clinical Immunology,
Volume 117, Issue 2, Hugh A. Sampson, Anne Muñoz-Furlong,
Ronna L. Campbell, et al, Second symposium on the definition and
management of anaphylaxis: summary report—Second National
Institute of Allergy and Infectious Disease/Food Allergy and
Anaphylaxis Network Symposium, Pages 391-397, Copyright 2006,
with permission from the American Academy of Allergy, Asthma &
Immunology. https://www.jacionline.org/
Copyright © 2019 EB Medicine. All rights reserved. 4
College of Allergy, Asthma & Immunology Epidemi-
ology of Anaphylaxis Working Group estimated the
lifetime prevalence of anaphylaxis from all causes to
be 0.05% to 2%.33 Anaphylaxis appears to be more
common in children than adults and is likely under-
reported in the youngest patients.2,33-35 Anaphylaxis
in infants may be missed because symptoms of facial
flushing, vomiting, and loose stool are nonspecific,
and these symptoms are easily attributed to other
diagnoses.35,36 After puberty, anaphylaxis appears to
be more common in women than men.37 In contrast,
studies in children show either a male predominance
or no gender difference.7,23,38-40
Several studies in the United States have demon-
strated a significant increase in ED visits for anaphy-
laxis,23,26,41 with the greatest increase seen among
children.21 Similar trends have been observed in
Europe,22,25 Australia,37,42 and Canada.43 Hospitaliza-
tion for anaphylaxis in children also appears to be
rising. Lin et al found a 4-fold increase in anaphylaxis
hospitalizations from 1990-2006,23 and Rudders et al
found that admissions for food-induced anaphylaxis
had doubled from 2000-2009.44
Biphasic Reactions
A biphasic reaction is the recurrence of anaphylactic
symptoms within 72 hours without re-exposure to
the trigger. Reported rates of biphasic reactions in
patients with anaphylaxis vary from 3% to 20%.45-52
This wide range can, in part, be explained by the va-
riety of definitions of anaphylaxis used in different
studies. Additionally, some studies included patients
who did not receive appropriate initial treatment
and some included patients with mild symptoms
not requiring intervention as having experienced
biphasic reactions.
Several studies have tried to determine risk factors
for a biphasic reaction. One study reported that no
biphasic reactions occurred in patients whose symp-
toms had completely resolved within 30 minutes of
initiation of treatment.45 In another study, all patients
with a biphasic reaction had required a second dose
of epinephrine or a fluid bolus during their initial
resuscitation.53 Several studies have identified the
need for higher total doses of epinephrine for symp-
tom resolution to be a risk factor for biphasic anaphy-
laxis.49,50,53 Another study found that patients with
biphasic reactions had a longer delay from the onset of
symptoms to epinephrine administration than patients
with uniphasic reactions.51,54 Two studies reported an
increased risk in patients requiring inhaled beta-ago-
nist treatment,50,52 and data from 27 studies found an
increased risk in patients with unknown inciting trig-
gers and initial hypotension.51 Based on current data,
the need for > 1 dose of epinephrine or a fluid bolus
(hypotension), slow response to epinephrine, a delay
in epinephrine administration, need for treatment with
inhaled beta agonists, and an unknown inciting trigger
Reprints: www.ebmedicine.net/pempissues
should be considered risk factors for biphasic reactions.
(See Table 3.)
Fatal Anaphylaxis
Despite the increase in prevalence and hospitalization
rates for anaphylaxis,23,41,44 death due to anaphylaxis
is rare (1 death per million people per year).22,25,26,42
Studies of pediatric patients who present to an ED
with anaphylaxis have demonstrated a mortality rate
of < 1%.26,53,55 This is consistent with other studies
of pediatric and adult populations, which have also
found the rate of fatal anaphylaxis to be < 1%.25,37,56-58
In the United States, fatality from anaphylaxis is more
frequent in elderly patients26,59 and is more common-
ly due to medications (59%) than food (7%).40
Risk factors for death from anaphylaxis are based
on limited data but seem to vary according to etiology.
Asthma and age appear to be risk factors for fatal food-
related anaphylaxis.22,34,59-64 In one study, all 13 pediatric
patients with fatal or near fatal food-related anaphylaxis
had asthma.60 Most food-related anaphylaxis deaths
seem to occur in adolescents and young adults.22,61,62
These patients are thought to be at higher risk at least in
part because they are less likely to avoid known triggers
or carry epinephrine autoinjectors.65 Recent data on fatal
anaphylaxis indicate that a known allergen, lack of or
delayed use of epinephrine, peanut or tree-nut allergen,
and maintenance of an upright posture during symp-
toms are also factors associated with increased risk of
fatality in food-related anaphylaxis.22,40,59 Older age and
underlying respiratory or cardiovascular disease have
been associated with increased risk for fatal drug-in-
duced anaphylaxis, and cardiovascular disease has also
been described as a risk factor for fatal venom-induced
anaphylaxis.59 (See Table 3.)
Table 3. Risk Factors for Biphasic Reactions
and Fatal Anaphylaxis
Biphasic Reactions
• The need for > 1 dose of epinephrine or a fluid bolus (hypotension)
• Slow response to epinephrine
• A delay in epinephrine administration
• The need for treatment with inhaled beta agonists
• Unknown inciting trigger and initial hypotension
Fatal Anaphylaxis
• Food-related anaphylaxis
Asthma
l
l Age, adolescent or young adult
l Known allergen
l Absence or delayed use of epinephrine
Peanut or tree-nut allergy
l
l Maintenance of an upright posture during symptoms
• Drug-induced anaphylaxis
Older age
l
Underlying respiratory or cardiovascular disease
l
• Venom-induced anaphylaxis
Cardiovascular disease
l
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June 2019 • www.ebmedicine.net
Although a large number of patients with anaphy-
laxis demonstrate cutaneous symptoms, in 2 case series
of fatal anaphylaxis, < 15% of patients had cutaneous
symptoms.60,66 It is unclear if this was due to chance,
if the lack of cutaneous symptoms is a marker for
severe anaphylaxis, or if recognition of anaphylaxis
and initiation of appropriate treatment was delayed
because urticaria was absent. Patients, families, and
clinicians must be aware that epinephrine is indicated
for patients with findings of anaphylaxis other than cu-
taneous symptoms so that epinephrine is administered
promptly, as delays are associated with fatal anaphy-
laxis.
Death appears to be uncommon if epinephrine is
administered immediately, but it has been reported.
Three of 48 patients in one series died despite appro-
priate self-administration of epinephrine.64 In another
case series, 2 of 32 deaths occurred in patients who had
not responded to self-administered epinephrine.61
Etiology and Pathophysiology
Anaphylaxis in children is most commonly due
to food, possibly due to an increased incidence of
food allergies in this age group.39,55,56 A review by
Sicherer and Sampson revealed the rate of food
allergy in children to be near 8%, compared to 5%
in adults.67 Recent studies have found an increase
in ED visits and hospitalizations for food-related
anaphylaxis.7,24,41,44,68,69 Peanuts and tree nuts are the
most common foods to cause anaphylaxis.7,55,56,70,71
Vaccine-related anaphylaxis is very rare, with an in-
cidence of about 1.5 cases per 1 million vaccinations
administered.72 In contrast to the predominance of
food-related anaphylaxis in children, anaphylaxis in
adults is more likely to be triggered by medications,
radiocontrast dye, or insect stings.40,59,66 Common
causes of anaphylaxis are listed in Table 4.
Table 4. Common Causes of Anaphylaxis
Foods
• Peanuts • Eggs
• Tree nuts • Sesame seeds/other sesame
• Shellfish products
• Fish • Food additives
• Milk
Medications
• Antibiotics
• Nonsteroidal anti-inflammatory drugs
Insects
• Hymenoptera (including bees, yellow jackets, wasps, and ants)
Used with permission from EB Medicine, publisher of Pediatric
Emergency Medicine Practice, from: Genevieve Santillanes
and Joshua Davidson. An Evidence-Based Review of Pediatric
Anaphylaxis. Pediatric Emergency Medicine Practice. 2010;7(10):1-
22. © 2010 EB Medicine.
5 Copyright © 2019 EB Medicine. All rights reserved.
Immune-Mediated Hypersensitivity
Immunoglobulin E (IgE) is central to the develop-
ment of anaphylaxis. Upon exposure to an allergen,
B cells become sensitized and produce allergen-
specific IgE. IgE binds to the Fc (fragment crystal-
lizable) epsilon R1 receptor found on basophils and
mast cells. When an allergen binds to the IgE-mast
cell complex, the mast cell releases mediators of the
anaphylactic response, including histamine, leukot-
rienes, and prostaglandins.34,73 Higher IgE levels
increase the probability that a reaction will occur
with re-exposure to the antigen.74 Furthermore, IgE
increases expression of its own receptor on basophils
and mast cells, creating a positive feedback loop, re-
sulting in a more vigorous anaphylactic response.74
Nonimmune-Mediated Hypersensitivity
Triggers such as radiocontrast dye, intravenous
N-acetylcysteine, ethanol, and opioids can induce
nonallergic anaphylactic (anaphylactoid) reactions.34
A heparin contaminant has been reported to cause
anaphylactoid reactions as well.75 The underly-
ing mechanism for anaphylactoid reactions is not
completely understood, but triggers appear to cir-
cumvent the classic IgE-mediated pathway, directly
activating basophils and mast cells to release media-
tors.74,76 Some triggers cause anaphylaxis via both
the traditional IgE-mediated and direct activation
pathways.34,77
Differential Diagnosis
The differential diagnosis of anaphylaxis varies de-
pending on the patient’s presentation.78 (See Table 5.)
Idiopathic or hereditary angioedema should be consid-
ered for patients with lip and tongue swelling. Various
causes of shock should be considered for patients with
hypotension. The differential diagnosis of urticaria is
broad. One unusual entity that may be considered in
the differential is cold-induced urticaria, a familial or
acquired disorder resulting in development of urticaria
with exposure to cold temperatures.

Table 5. Differential Diagnosis by Predominant Symptom

Predominant Symptom Differential Diagnosis
Rash • Isolated urticaria • Viral syndrome
• Contact dermatitis • Henoch-Schönlein purpura
• Erythroderma (toxic shock syndrome or other • Erythema multiforme
etiology) • Cutaneous drug reaction
• Carcinoid syndrome • Mastocytosis

Dyspnea/wheeze/stridor/hypoxia • Asthma/chronic obstructive pulmonary disease • Pulmonary embolism

• Croup • Congestive heart failure
• Choking event • Panic attack
• Foreign body aspiration • Psychogenic stridor
• Epiglottitis

Angioedema (oral) • Angioedema due to ACE inhibitor • Hereditary angioedema

Angioedema (eyes) • Simple allergic reaction • Infection (blepharitis, periorbital cellulitis)

• Nephrotic syndrome

Dizziness/syncope/near-syncope • Seizure • Vertebral basilar insufficiency

• Postural orthostatic tachycardia syndrome • Central vertigo
• Syncope (vasovagal, cardiogenic) • Dehydration
• Arrhythmia • Breath-holding spell

Chest pain • Myocardial disease • Aortic dissection

• Arrhythmia

Hypotension • Septic shock • Hypovolemic shock

• Myocarditis/other cardiogenic shock • Unrecognized trauma

Vomiting/diarrhea/abdominal cramping • Gastroenteritis • Mastocytosis

• Food poisoning • Carcinoid syndrome

Dysphagia • Caustic ingestion • Esophageal foreign body

Altered level of consciousness • Stroke • Intracranial hemorrhage

• Drug/alcohol ingestion • Cerebral contusion
• Meningitis/encephalitis • Hypoxia
• Postictal state • Psychogenic

Abbreviation: ACE, angiotensin-converting enzyme.

Reprinted by permission from Springer Nature Customer Service Centre GmbH: Springer Nature. Life-Threatening Rashes. Edited by Emily Rose.
© 2018. https://www.springer.com/us/book/9783319756226

Copyright © 2019 EB Medicine. All rights reserved. 6 Reprints: www.ebmedicine.net/pempissues

Scombroid Poisoning
Scombroid poisoning is easily misdiagnosed as
anaphylaxis. Scombroid poisoning is thought to be
caused by high levels of histamine in poorly refriger-
ated fish. Histidine, naturally present in the flesh of
fish, is broken down by bacteria to histamine. Inad-
equate refrigeration accelerates this process. The fish
may not appear spoiled, and it can taste and smell
normal. Symptoms occur within minutes to hours of
consumption and may include a peppery taste in the
mouth, burning or tingling of the oral mucosa, head-
ache, dizziness, flushing, sweating, rash, pruritus,
abdominal cramping, diarrhea, nausea, and vomit-
ing.79,80 Patients may have hypotension, tachycardia,
and circulatory collapse.
The time course and symptoms of scombroid
poisoning and anaphylaxis are very similar. Since
seafood is a common cause of anaphylaxis, the
diagnosis is challenging. If > 1 person presents
with anaphylactic-like symptoms after eating fish,
scombroid poisoning is likely. Scombroid poisoning
should also be considered in patients with apparent
anaphylaxis who have previously eaten the same
fish multiple times without any allergic symptoms.
If there is any question whether symptoms are due
to scombroid poisoning or anaphylaxis, referral to
an allergist for testing is appropriate.
Mastocytosis
Mastocytosis is a chronic disorder that can mimic or
cause anaphylactic reactions. Cutaneous mastocyto-
sis is due to proliferation of mast cells in the skin.81 It
is characterized by reddish-brown macules, papules,
plaques, or blisters that develop urticaria in response
to physical trauma. Systemic mastocytosis occurs
when mast cells proliferate in other tissues including
the bone marrow, liver, spleen, and lymph nodes.81
Usual signs and symptoms of systemic mastocytosis
overlap with signs and symptoms of anaphylaxis.
Flushing, pruritus, abdominal pain, diarrhea, dys-
pnea, and tachycardia are seen in both. Patients with
recurrent, idiopathic anaphylaxis may in fact have
underlying mastocytosis.81 Systemic mastocytosis is
rare in children but might be considered with recur-
rent, otherwise unexplained anaphylaxis. Anaphy-
laxis can occur in patients with both cutaneous and
systemic mastocytosis, and it has been reported in
children with severe diffuse cutaneous mastocyto-
sis.82
Prehospital Care
Anaphylaxis is an uncommon reason for emer-
gency medical services (EMS) transport, with a chief
complaint of allergy or anaphylaxis accounting for
only 0.2% to 0.5% of EMS calls.83-86 Prehospital care
should focus on the ABCs (airway, breathing, and cir-
culation). Supplemental oxygen should be supplied
June 2019 • www.ebmedicine.net
as needed for hypoxia, and intravenous (IV) fluids
should be given for hypotension or other evidence
of shock.13 Intramuscular (IM) epinephrine should
be administered as soon as possible in patients with
evidence of anaphylaxis.16,54,60-62 Epinephrine admin-
istration is generally incorporated into paramedic
advanced life support protocols. Small studies have
demonstrated that emergency medical technicians
administered epinephrine to appropriate patients
and that administration by emergency medical tech-
nicians was safe.87,88
Although paramedics are trained in adminis-
tration of epinephrine, anaphylaxis is often under-
recognized and undertreated by EMS personnel.
Three pediatric studies found that < 30% of patients
meeting criteria for anaphylaxis were administered
epinephrine by EMS,5,89,90 with children aged < 10
years less likely to receive epinephrine appropri-
ately.90 One national survey study also found that
while a large percentage of EMS providers correctly
recognized classic anaphylaxis, only 2.9% correctly
identified atypical anaphylaxis.91 Only 46.2% of
EMS providers identified epinephrine as the initial
drug of choice for anaphylaxis, and 36.2% stated that
there were contraindications to epinephrine admin-
istration in anaphylactic shock.91
Delay in the administration of epinephrine has
been associated with hypoxic-ischemic encephalopa-
thy and fatal anaphylaxis.54,60,62 One study on fatal
anaphylaxis showed that the median time to respi-
ratory or cardiac arrest was 30 minutes for foods,
15 minutes for venom, and 5 minutes for iatrogenic
reactions.63 In half of the fatalities in another study,
death occurred within 60 minutes of exposure.66
Given the increasing incidence of anaphylaxis and
the potential for rapid decompensation, early pre-
hospital treatment is critical.
Emergency Department Evaluation
History
After stabilization, the trigger for the anaphylactic
event should be identified, if possible. Important
information to obtain includes a list of all foods and
medications consumed several hours before the
reaction (symptoms can present within minutes to
hours after exposure to a trigger60) and any possible
insect stings or bites. Ask about any chronic medica-
tions (eg, beta blockers) that might affect response to
treatment. Comorbid diseases such as asthma may
affect the severity of the reaction and disposition
decisions. Ask about any previous allergic reactions.
Patients with a previous anaphylactic reaction may
have self-administered epinephrine before arrival
to the ED; if this is the case, ask about the timing of
administration and the response to the medication.
7 Copyright © 2019 EB Medicine. All rights reserved.
Physical Examination
Anaphylaxis is an acute systemic reaction that usually
affects 2 or more organ systems. Initial symptoms may
be mild but can rapidly progress to a severe, life-threat-
ening reaction. The most common signs and symptoms
of an anaphylactic reaction are dermatologic and respi-
ratory.38 All patients with possible anaphylaxis should
immediately have their vital signs checked, with
particular attention paid to blood pressure and oxygen
saturation. The general assessment should focus on
signs of altered mental status, shock, and respiratory
distress. Signs of airway obstruction, including stridor,
wheezing, and decreased air movement, may be noted.
Airway patency and the patient’s ability to protect the
airway should be assessed. Evidence of posterior oro-
pharyngeal swelling should raise concern for impend-
ing airway obstruction.
Most patients present with mucocutaneous symp-
toms such as urticaria, flushing, or angioedema.46,56
A minority of patients lack cutaneous manifesta-
tions.37,38,46,56,66 Patients may present with predomi-
nantly gastrointestinal or neurologic symptoms (eg,
syncope or dizziness due to hypotension). For patients
who are unable to provide a history, examine the skin
for signs of an insect sting or bite, which may be the
trigger for the reaction. Reddish-brown papules or
macules that become raised, red, and itchy after strok-
ing may be indicative of mastocytosis.
Infants represent a significantly vulnerable
population since they are unable to describe the sub-
jective symptoms used to diagnose anaphylaxis.1,36
Age-appropriate criteria should be used to assess for
tachycardia and hypotension in pediatric patients.8
Atypical Anaphylaxis
The wide range of potential signs and symptoms can
make the diagnosis of atypical anaphylaxis chal-
lenging.1,8 When anaphylaxis occurs without skin
findings, it may not be recognized initially, delay-
ing diagnosis and treatment. In a postmortem case
review of fatal anaphylaxis, only 4 of 25 patients had
cutaneous findings (pruritus, urticaria, flushing).66
Patients with anaphylaxis can present with symp-
toms not meeting the full criteria for anaphylaxis, or
have mild symptoms, and yet require administration
of epinephrine.15 Severe symptoms in a single organ
system, or mild symptoms in a person with a known
allergen exposure and a previous history of anaphy-
laxis, can also represent anaphylaxis.14,15,92 Prompt
recognition and treatment with epinephrine, even in
uncertain cases, may prevent rapid progression to
respiratory or cardiovascular arrest.14
Diagnostic Studies
Anaphylaxis is a clinical diagnosis. Since anaphy-
laxis must be treated immediately, laboratory tests
are not helpful in ED management.
Copyright © 2019 EB Medicine. All rights reserved. 8
Treatment
Epinephrine
Epinephrine is the most important medication in
the treatment of anaphylaxis, as it has multiple
potential benefits. Epinephrine increases peripheral
vascular resistance and has positive chronotropic
and inotropic cardiac effects, thereby treating
anaphylaxis-associated hypotension. Peripheral
vasoconstriction reduces flushing, urticaria,
and angioedema, and beta-adrenergic effects of
epinephrine treat associated bronchospasm.18 In
addition to the immediate cardiorespiratory effects,
epinephrine is thought to decrease further release of
inflammatory mediators from basophils and mast
cells, and may play a role in preventing biphasic or
late reactions.18,93
While epinephrine is clinically considered
beneficial in the treatment of anaphylaxis, a rigorous
evidence base is lacking. A Cochrane review of the
use of epinephrine in anaphylaxis found no random-
ized or quasi-randomized trials.28 Since epinephrine
is accepted as effective, and untreated anaphylaxis is
potentially fatal, a randomized controlled trial com-
paring epinephrine and a placebo cannot be justified
ethically. However, there is indirect evidence that
epinephrine is effective in the treatment of anaphy-
laxis. Early treatment with epinephrine before ED
arrival has been associated with decreased length
of stay in the ED,94 lower risk of hospitalization,94
and a reduced risk of requiring multiple doses of
epinephrine.43 Delayed administration of epineph-
rine has been associated with fatal and biphasic
anaphylaxis.54,60 In a study of fatal anaphylaxis in
children, all 6 children with fatal anaphylaxis had a
significant delay from the time of allergen exposure
to administration of epinephrine.60 The vast majority
of patients described in 2 series of fatal anaphylaxis
did not receive early epinephrine.61,62
Despite being the recommended first-line treat-
ment, epinephrine is often underused. Retrospective
studies of ED treatment of anaphylaxis in adults and
children have found rates of epinephrine adminis-
tration ranging from 12% to 67%.37,39,95-97 A study of
the European Anaphylaxis Registry found that while
ED epinephrine administration increased from 12%
to 24% over the study period, the majority of pa-
tients did not receive epinephrine.98 Multiple studies
have found that patients diagnosed with anaphy-
laxis are much more likely to receive corticoste-
roids and antihistamines than epinephrine.2,5,95,96,99
Furthermore, one pediatric study found that the
majority of ED epinephrine doses were incorrectly
administered subcutaneously rather than IM.99
Not only is epinephrine underused in the ED set-
ting, but patients themselves underuse their epineph-
rine autoinjectors. One study found that, although
86% of pediatric patients stated they carried their
Reprints: www.ebmedicine.net/pempissues
epinephrine autoinjector at all times, only 55% carried
an unexpired injector at their allergy clinic visit.100 A
large longitudinal pediatric study found that among
patients who did carry an epinephrine autoinjector at
the time of anaphylactic symptom development, only
50% of them used it before ED arrival.43 Similarly,
Ben-Shoshan et al found that among patients with
moderate to severe anaphylaxis who had an epineph-
rine autoinjector at the time of symptom develop-
ment, 33% did not use it.101 Parents of patients in
that study stated they either “panicked, had a fear of
needles, or were hesitant to use it.”101
Intramuscular Epinephrine
All guidelines recommend early treatment of ana-
phylaxis with IM epinephrine.1,12-18 There are no
absolute contraindications to the administration of
epinephrine in the setting of anaphylaxis.15 Pediatric
dosing is 0.01 mg/kg of the 1 mg/mL concentration
administered IM, to a maximum of 0.5 mg.102 IM
administration of epinephrine results in more rapid
achievement of peak plasma epinephrine levels than
subcutaneously administered epinephrine.103,104
Data in adults support the administration of epi-
nephrine in the upper vastus lateralis muscle.104 Ad-
ministering the appropriate epinephrine autoinjector
dosing (0.1 mg, 0.15 mg, or 0.3 mg) is also an option.
Intravenous Epinephrine
Most cases of anaphylaxis respond to IM epinephrine,
which is the safest route of administration in general.
However, in cases of hypotension refractory to repeat-
ed doses of IM epinephrine, the IV route may be con-
sidered. Evidence-based IV dosing recommendations
are not available, and recommended doses vary. The
report from the Second Symposium on the Definition
and Management of Anaphylaxis recommends bolus
doses of 0.2 mcg/kg to a maximum of 10 mcg for
persistent hypotension.1 The Resuscitation Council
(UK) guidelines give the option of IV bolus doses of 1
mcg/kg of 0.1 mg/mL epinephrine to a maximum of
50 mcg of IV epinephrine in cases requiring repeated
IM doses of epinephrine.16 Other experts recommend
epinephrine infusions rather than bolus doses.34
Epinephrine Dosing Errors
Multiple case reports describe epinephrine dosing
errors in patients with anaphylaxis, including inad-
vertent IV administration of the 1 mg/1 mL formu-
lation or IV administration of cardiac-arrest dosing
of epinephrine.63,105-108 One study demonstrated that
the risk of overdose with IV bolus epinephrine was
61 times greater than with IM epinephrine.109 Seri-
ous outcomes after epinephrine overdose in chil-
dren and young adults without underlying cardiac
disease are unusual but have been described in case
reports. While it is unknown if reported complica-
tions are due to epinephrine overdose or the hypoxia
June 2019 • www.ebmedicine.net
or hypotension that led to epinephrine administra-
tion, epinephrine overdose does have the potential
to cause serious harm. In one case, a 13-year-old girl
developed fatal pulmonary edema after IV admin-
istration of 3.5 mg of epinephrine.63 Another case
report described a 5-year-old boy who developed
ventricular dysrhythmias and myocardial ischemia
after receiving a 10-fold overdose of subcutaneous
epinephrine.107 A case of takotsubo cardiomyopathy
has also been reported in a 24-year-old woman after
an overdose of IM epinephrine.108
Reasons for dosing errors are likely multifacto-
rial. The 1 mg/mL concentration of epinephrine is
less familiar than the 0.1 mg/mL concentration. A
concept paper published in the Annals of Emergency
Medicine recommends that EDs add easy-to-read
labels to epinephrine syringes to distinguish IM
and IV preparations in order to avoid inadvertent
IV administration of concentrated epinephrine.105
Expression of the concentration as a ratio (1:1000)
can be confusing because clinicians are more accus-
tomed to mass concentrations (1 mg/mL). One study
found that clinicians took longer to calculate doses
and were more likely to give an incorrect dose when
calculating doses using ratios rather than mass con-
centrations.110 Additionally, calculation of weight-
based pediatric doses introduces additional potential
errors; computerized emergency dosing calculators
may decrease dosing errors.111,112
Antihistamines
Antihistamines are commonly recommended for
the treatment of anaphylaxis.1,16,113,114 However, a
Cochrane review of H1-receptor blockers in anaphy-
laxis did not identify any randomized or quasi-ran-
domized trials to support this statement.27 A system-
atic review of H2-receptor blockers in anaphylaxis
yielded similar results.115 Antihistamines are consid-
ered a second-line treatment and should never delay
or replace epinephrine administration.
A study of ED patients with allergic reactions
found that those who received an H1 antihistamine
had a lower likelihood of progression to anaphylax-
is.116 Studies in adults demonstrate that the combi-
nation of H1- and H2-receptor blockers is superior
to an H1-receptor blocker alone in the treatment of
cutaneous symptoms of mild allergic reactions.117,118
Antihistamines do not relieve respiratory compro-
mise, shock, or hypotension, but may be useful as
a second-line agent to treat cutaneous symptoms of
anaphylaxis. Additionally, administration of an-
tihistamines before IV radiocontrast may prevent
anaphylactoid reactions.119,120 There is no evidence
to guide duration of treatment and expert guideline
recommendations vary.1,8,15,16,113,121 (See Table 6,
page 12.)
9 Copyright © 2019 EB Medicine. All rights reserved.
 Clinical Pathway for Diagnosis of Anaphylaxis in Pediatric Patients1

Does the patient have acute onset of the following without a more
plausible explanation?
• Mucocutaneous signs (urticaria, generalized flushing,
pruritus, angioedema)
AND 1 of the following YES Proceed to the Pathway for Treatment of Anaphylaxis, page 11
• Respiratory compromise (wheeze, stridor, hypoxemia,
dyspnea) or hypotension, collapse, syncope, incontinence

NO

Does the patient have at least 2 of the following AFTER recent

exposure to a likely allergen?
• Mucocutaneous signs (urticaria, generalized flushing,
pruritus, angioedema)
• Respiratory compromise (wheeze, stridor, hypoxemia,
YES Proceed to the Pathway for Treatment of Anaphylaxis, page 11
dyspnea)
• Hypotension, collapse, syncope, incontinence
• Persistent gastrointestinal symptoms (vomiting, crampy
abdominal pain)

NO

Does the patient have a known allergen AND hypotension (or a

decrease of ≥ 30% from baseline blood pressure) within hours
YES Proceed to the Pathway for Treatment of Anaphylaxis, page 11
of exposure to that allergen?

NO

Consider alternate diagnoses

Adapted from: Genevieve Santillanes and Joshua Davidson. An Evidence-Based Review of Pediatric Anaphylaxis. Pediatric Emergency
Medicine Practice. 2010;7(10):1-22. © 2010, with permission from EB Medicine.

Copyright © 2019 EB Medicine. All rights reserved. 10 Reprints: www.ebmedicine.net/pempissues

 Clinical Pathway for Treatment of Anaphylaxis in Pediatric Patients in the
Emergency Department

Is the patient in cardiopulmonary arrest? YES Initiate Pediatric Advanced Life Support or Advanced Cardiac
Life Support
NO
Administer IM epinephrine (1 mg/mL)
0.01 mg/kg to the anterolateral thigh,
maximum 0.3-0.5 mg (Class II)
AND
Provide oxygen and airway management as needed
Consider:
• An H1-receptor blocker for cutaneous symptoms
(Class III)
Are life-threatening symptoms of hypotension,
YES • An H2-receptor blocker for cutaneous symptoms
respiratory distress, or stridor resolved?
(Class III)
• A corticosteroid to prevent biphasic reactions
NO
(Indeterminate)

• Repeat epinephrine every 3-5 minutes as

necessary
• Give IV fluid bolus as necessary
If the patient does not have risk factors for fatal or biphasic
• Consider inhaled beta agonists for persistent
anaphylaxis, observe for 4-6 hours and discharge with an
wheezing
epinephrine autoinjector or a prescription for an autoinjector

Have the symptoms resolved? YES Consider admission to a monitored bed

NO

Consider IV epinephrine (0.1 mg/mL) boluses or

an epinephrine drip for persistent hypotension
0.2 mcg/kg, maximum 10 mcg/dose

Admit to pediatric intensive care unit

Abbreviations: IM, intramuscular; IV, intravenous; PO, by mouth.

Adapted from: Genevieve Santillanes and Joshua Davidson. An Evidence-Based Review of Pediatric Anaphylaxis. Pediatric Emergency Medicine
Practice. 2010;7(10):1-22. © 2010, with permission from EB Medicine.

Class of Evidence Definitions

Each action in the clinical pathways section of Pediatric Emergency Medicine Practice receives a score based on the following definitions.
Class I Class II Class III Indeterminate
• Always acceptable, safe • Safe, acceptable • May be acceptable • Continuing area of research
• Definitely useful • Probably useful • Possibly useful • No recommendations until further
• Proven in both efficacy and effectiveness • Considered optional or alternative treat- research
Level of Evidence: ments
Level of Evidence: • Generally higher levels of evidence Level of Evidence:
• One or more large prospective studies • Nonrandomized or retrospective studies: Level of Evidence: • Evidence not available
are present (with rare exceptions) historic, cohort, or case control studies • Generally lower or intermediate levels of • Higher studies in progress
• High-quality meta-analyses • Less robust randomized controlled trials evidence • Results inconsistent, contradictory
• Study results consistently positive and • Results consistently positive • Case series, animal studies, • Results not compelling
compelling consensus panels
• Occasionally positive results

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2019 EB Medicine. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Medicine.

June 2019 • www.ebmedicine.net 11 Copyright © 2019 EB Medicine. All rights reserved.

Corticosteroids
Anaphylaxis guidelines recommend treatment with
corticosteroids as second-line therapy for patients
with anaphylaxis, despite a lack of strong support-
ing evidence.1,16,113,121 Corticosteroids have a slow
onset of action and are not effective in the immediate
management of acute anaphylaxis. Corticosteroids
are theorized to prevent biphasic or protracted
reactions. However, a Cochrane review of gluco-
corticoids for the treatment of anaphylaxis did not
identify any randomized controlled trials (in adults
or children) to support this statement.30 Two retro-
spective studies found that similar proportions of
pediatric patients with biphasic and uniphasic reac-
tions received corticosteroids, but administration of
corticosteroids did not appear to protect against the
development of biphasic reactions.53,54 A prospec-
tive study of patients with biphasic reactions found
a statistically insignificant trend toward a decreased
incidence of biphasic reaction in patients receiv-
ing corticosteroids.45 These were studies with small
numbers of patients with biphasic reactions. Larger
prospective studies are needed to determine if corti-
costeroid use alters the risk of developing a biphasic
reaction.
A large retrospective study of children hospi-
talized with anaphylaxis found that early admin-
istration of glucocorticoids was associated with a
decreased length of stay, as well as a reduction in
recurrent epinephrine administration, supporting
the use of glucocorticoids in pediatric patients who
are hospitalized with anaphylaxis.122
As with antihistamines, all guidelines empha-
Table 6. Expert Guideline Recommendations on Antihistamines for Treatment of Anaphylaxis
Organization
Joint Task Force representing the American Academy of
Allergy, Asthma & Immunology; the American College
of Allergy, Asthma & Immunology; and the Joint Council
of Allergy, Asthma and Immunology15,121
National Institute of Allergy and Infectious Diseases,
Food Allergy and Anaphylaxis Network,1 and World
Allergy Organization8
European Academy of Allergology and Clinical
Immunology113
Resuscitation Council (UK)16
Abbreviations: IV, intravenous; PO, by mouth.
Adapted from: Genevieve Santillanes and Joshua Davidson. An Evidence-Based Review of Pediatric Anaphylaxis. Pediatric Emergency Medicine
Practice. 2010;7(10):1-22. © 2010, with permission from EB Medicine.
Copyright © 2019 EB Medicine. All rights reserved. 12
size that corticosteroids are an optional or second-
line treatment for anaphylaxis and should never
delay or replace the administration of epinephrine.
There is no evidence to guide the duration of cortico-
steroid therapy.1,16,113,121 (See Table 7, page 13.)
For more information on corticosteroids as treat-
ment for anaphylaxis, see the March 2018 issue of Pe-
diatric Emergency Medicine Practice, “Corticosteroid Use
in Management of Pediatric Emergency Conditions,”
available at: www.ebmedicine.net/corticosteroids.
Airway Management
A literature search did not find any studies of
airway management in ED patients (adults or
children) with anaphylaxis. Recommendations
from the Joint Task Force guidelines on anaphylaxis
include preparing for airway management, includ-
ing intubation if necessary, if there are any signs of
airway edema or associated respiratory compro-
mise.15 Clinicians must rely on their best judgment
in airway management. Airway edema may worsen
if anaphylaxis is progressive despite appropriate
treatment, and early intubation may be beneficial.
Patients with mucosal edema should be considered
to have difficult airways, and paralytics should be
used with caution in these patients. Upper air-
way edema can significantly hinder mask rescue
ventilation. Management of the difficult airway is
beyond the scope of this review, but alternatives to
traditional orotracheal intubation (eg, a fiber optic
laryngoscope and a cricothyrotomy kit) should be
available if tracheal intubation is attempted.
Recommendations for H1-Receptor Recommendations for H2-Receptor
Blockers Blockers
• Considered second-line • Considered second-line
• Diphenhydramine 1-2 mg/kg to 50 mg • Ranitidine 1 mg/kg to 50 mg IV
parenterally, slow infusion
• Second-line treatment • Second-line treatment
• Diphenhydramine 1-2 mg/kg to 50 mg • Ranitidine 1 mg/kg to 50 mg either IV or
parenterally or PO in mild cases PO in mild cases
• Recommended options: • Not adequately tested in children
chlorpheniramine, cetirizine,
levocetirizine, loratadine, desloratadine,
or fexofenadine
• Recommended as second-line • Insufficient evidence to support routine
• Chlorpheniramine PO dosing: use
l
> 12 years: 10 mg
l
6-12 years: 5 mg
l 6 months-6 years: 2.5 mg
l < 6 months: 250 mcg/kg
Reprints: www.ebmedicine.net/pempissues
Special Circumstances
Beta Blockers
Epinephrine increases cyclic adenosine monophos-
phate (cAMP) through beta-adrenergic stimulation,
and this pathway is less effective in patients taking
beta blockers. Case reports have been published
that describe patients taking beta blockers who had
unusually severe or treatment-refractory anaphylax-
is.123 Two retrospective case-control studies demon-
strated an increased risk of moderate or severe ana-
phylactoid reactions after radiocontrast exposure in
patients taking beta blockers.124,125 However, a study
of ED patients demonstrated that patients taking
beta blockers did not require more doses of epineph-
rine compared to those not taking beta blockers.126
Glucagon has been proposed as a treatment for
epinephrine-resistant anaphylactic shock in patients
taking beta blockers because glucagon increases
cAMP via alternate pathways and has chronotropic
and inotropic effects that are unaffected by beta
blockers.127 Several case reports describe patients
taking beta blockers who developed radiocontrast-
induced hypotension that was refractory to usual
treatment, but whose hypotension was reversed
after glucagon administration.128,129
Sufficient evidence is not available to change
recommendations for treatment of anaphylaxis in
patients taking beta blockers. To our knowledge, use
of glucagon in anaphylaxis or an anaphylactoid reac-
tion has never been described in a pediatric patient.
However, in patients failing usual treatment, glu-
cagon may be considered. One practice parameter
recommends a pediatric dose of 20 to 30 mcg/kg, to
a maximum dose of 1 mg.121
Table 7. Expert Guideline Recommendations on Corticosteroids for Treatment of Anaphylaxis
Organization
Joint Task Force representing the American Academy of Allergy, Asthma
& Immunology; the American College of Allergy, Asthma & Immunology;
and the Joint Council of Allergy, Asthma and Immunology121
National Institute of Allergy and Infectious Diseases, Food Allergy and
Anaphylaxis Network1
European Academy of Allergology and Clinical Immunology113
Resuscitation Council (UK)16
Abbreviations: IM, intramuscular; IV, intravenous; PO, by mouth.
Adapted from: Genevieve Santillanes, and Joshua Davidson. An Evidence-Based Review of Pediatric Anaphylaxis. Pediatric Emergency Medicine
Practice. 2010;7(10):1-22. © 2010, with permission from EB Medicine.
June 2019 • www.ebmedicine.net
Exercise-Induced Anaphylaxis
Exercise-induced anaphylaxis occurs only during ex-
ercise.130 Another variant, food-dependent exercise-
induced anaphylaxis, occurs during exercise only
after eating certain foods normally tolerated by the
patient.131 Wheat has been the most commonly im-
plicated cause of food-dependent exercise-induced
anaphylaxis, but multiple foods may be causative.
Emergent treatment for exercise-induced anaphy-
laxis is the same as for other forms of anaphylaxis.
Controversies and Cutting Edge
Alternate Routes of Epinephrine Administration
In 2017 the FDA approved a 0.1 mg epinephrine autoin-
jector with a shorter needle for use in infants and small
children weighing 7.5 to 15 kg. For more information, see
the "Epinephrine Autoinjector Doses" section, page 15.
Vasopressin
Most cases of pediatric anaphylaxis respond well
to epinephrine and IV fluids. The evidence base for
treatment of epinephrine-resistant anaphylaxis is
lacking. There are multiple adult case reports of suc-
cessful use of vasopressin in patients with anaphy-
laxis that is resistant to usual treatment.132,133 The
dose administered in most case reports ranged from
2 to 10 international units, given as an IV bolus dose.
No guidelines incorporate the use of vasopressin
for treatment of anaphylaxis in children, and, at this
time, there are no dosing recommendations. While
further research is needed, vasopressin is an option
for patients with anaphylaxis that is refractory to
epinephrine and IV fluids.
Recommendations
Consider for patients with a history of idiopathic anaphylaxis or asthma
and patients with severe or prolonged symptoms:
• Glucocorticosteroids 1-2 mg/kg/day IV, given every 6 hours
• For less critical patients: prednisone 0.5 mg/kg PO
Options:
• Methylprednisolone 1-2 mg/kg/dose IV, given every 6 hours
or
• Prednisone 1 mg/kg PO for milder attacks
• Not considered first-line
• Methylprednisolone or hydrocortisone as IV options
Recommended:
• Hydrocortisone IV or IM
l > 12 years: 200 mg
l 6-12 years: 100 mg
l 6 months-6 years: 50 mg
l < 6 months: 25 mg
13 Copyright © 2019 EB Medicine. All rights reserved.
Extracorporeal Membrane Oxygenation posure to the trigger and a sixth patient died 5 hours
In two adult case reports,134,135 early initiation of after exposure.60 In that study, 3 of the patients had
extracorporeal membrane oxygenation (ECMO) has improvement in symptoms before dying. These 2
been successful in resuscitating patients with severe studies of fatal anaphylaxis support a 6-hour obser-
anaphylaxis that is refractory to standard treatments. vation period for patients with anaphylaxis.
While there are no similar case reports for pediatric
patients, we recommend considering the early use Admission
of ECMO for severe cases of anaphylaxis that do not The decision of whether or not to admit the pa-
respond to aggressive resuscitative measures. tient should be based on the severity of symptoms,
response to treatment, risk factors for severe or fatal
Disposition
Table 8. Expert Guideline Recommendations
Emergency Department Observation on Duration of Observation of Patients With
The statement published by the National Institute of Anaphylaxis
Allergy and Infectious Diseases/Food Allergy and
Organization Recommendations
Anaphylaxis Network with input from the American
College of Emergency Physicians and the American National Institute of • 4-6 hours for most patients
Academy of Pediatrics states that an observation Allergy and Infectious • Individualized, based on severity
period of at least 4 to 6 hours is appropriate for most Disease, Food Allergy of initial reaction, access to care,
patients.1 All guidelines state that longer observation and Anaphylaxis reliability of patient
Network Symposium1 • Admission or prolonged observation
periods may be considered for patients with severe
of patients with refractory or severe
reactions or those who have risk factors for biphasic or
symptoms
fatal anaphylaxis. (See Table 8 and Table 3, page 5.) • Caution in patients with reactive
airway disease
Biphasic Reactions
World Allergy • 4-6 hours for most patients
A period of observation is generally indicated to Organization8 • 8-10 hours for respiratory or
observe for evidence of a biphasic reaction and to cardiovascular compromise
initiate early treatment. Prolonged observation could • Admit for severe or protracted
be avoided if at-risk patients can be accurately identi- anaphylaxis
fied. Guidelines vary in their recommendations for European Academy • 6-8 hours for respiratory symptoms
observation time due to limited data on incidence and of Allergy and • 12-24 hours for hypotension or
clinical predictors of biphasic reactions. The length of Clinical Immunology collapse
time to development of a biphasic reaction varies con- Taskforce12
siderably from study to study.45,49-51,53,54,97 In a pedi- Joint Task Force on • 4-8 hours for most patients
atric study of 71 patients with biphasic reactions, 75% Practice Parameters15 • Individualized, based on the same
of the patients had recurrence of symptoms within 5 criteria used to determine need for
hours after initial symptoms, and the remaining 25% admission
had recurrence within a median time of 18.5 hours.50 • Consider longer observation for ingested
In a review of 192 patients with biphasic reactions, the allergens, requirement of > 1 dose of
median time of recurrence of symptoms was 11 hours epinephrine, hypotension, pharyngeal
with a range from 0.2 to 72 hours.51 The authors of an edema, or a history of asthma

inpatient study concluded that only 2% of hospital- Resuscitation Council • At least 6 hours
ized patients benefitted from admission for 24-hour (UK)16 • Consider up to 24 hours if:
observation.54 Multiple authors have described pa- Severe, idiopathic anaphylaxis with
l

tients with biphasic reactions after an asymptomatic slow onset

period of > 24 hours. Therefore, there is a small risk Patient has severe asthma or a
l

history of biphasic reactions

of deterioration after discharge even if patients are
Possible continued allergen
admitted for 24 hours of observation.45,54,136
l

absorption
Patient has difficulty responding
l

Fatal Anaphylaxis
to any deterioration, resides in
In a study of 164 cases of fatal anaphylaxis, the
a geographic area without easy
longest time from exposure to the trigger to death access to emergency care, or is
was 6 hours.63 The vast majority of deaths occurred presenting to the ED in the evening
within 4 hours of exposure to the trigger. The major- or at night
ity of delayed deaths were due to ingested allergens.
Adapted from: Genevieve Santillanes and Joshua Davidson.
(See Figure 1, page 15.) A study of 6 children with
An Evidence-Based Review of Pediatric Anaphylaxis. Pediatric
fatal food-related anaphylaxis demonstrated similar Emergency Medicine Practice. 2010;7(10):1-22. © 2010, with
results; 5 of the children died within 4 hours of ex- permission from EB Medicine.

Copyright © 2019 EB Medicine. All rights reserved. 14 Reprints: www.ebmedicine.net/pempissues

anaphylaxis, previous biphasic reaction, and patient
reliability.1,8,12,13,15,16 (See Table 8, page 14.) Admis-
sion to an intensive care unit is indicated for patients
with treatment-resistant anaphylaxis.
Discharge Medications and Referrals
Many studies demonstrate a need for improvement
in ED discharge medications and instructions for pa-
tients with anaphylaxis. One study of patients with
food allergies showed that only 35% of patients with
food-related anaphylaxis were given instructions to
avoid the offending food.95 In the United States, 22%
to 63% of patients diagnosed with anaphylaxis were
discharged with an epinephrine autoinjector and
13% to 33% were referred to an allergist.70,95,96,99 An
Australian study found that only 17.5% of pediatric
patients with anaphylaxis were discharged with a
prescription for an epinephrine autoinjector, but 54%
of children were discharged with a prescription for
an H1-receptor blocker, and 28% were discharged
with a prescription for steroids.39
Guidelines recommend prescribing an epineph-
rine autoinjector and offering training on how to
use it, providing instructions on avoidance of the
offending allergen (if known), and referring the
patient to a specialist in allergy and immunology on
discharge from the ED. Additionally, since there is a
small risk of recurrent symptoms after discharge, the
child should be discharged to a reliable adult who is
able to administer the epinephrine autoinjector and
access emergency services in case of a biphasic reac-
tion.
Epinephrine Autoinjector Doses
Until recently, epinephrine autoinjectors have been
available in 2 doses in the United States, 0.15 mg and
0.3 mg. United States Food and Drug Administration
Figure 1. Time to Cardiac Arrest Following
Exposure to Triggering Agent
Richard SH Pumphrey. Fatal Anaphylaxis in the UK, 1992–2001.
Anaphylaxis: Novartis Foundation Symposium 257, Volume
257. Pages 116-132. Copyright Novartis Foundation, 2004, with
Permission from John Wiley and Sons.
June 2019 • www.ebmedicine.net
(FDA)-approved drug labels for autoinjectors state
that the 0.15 mg dose should be used for children
weighing > 15 kg and < 30 kg, and the 0.3 mg dose
should be used for children weighing ≥ 30 kg. How-
ever, this would result in a significant underdose in
children weighing close to 30 kg. Children receiving
larger doses of epinephrine experience more side
effects from the medication,137 but given the risks of
undertreated anaphylaxis, a small overdose may be
preferable to an underdose. One expert review states
that most allergists dispense the 0.15 mg autoinjec-
tor to children who weigh 10 kg to 20 kg and the 0.3
mg autoinjector to children who weigh ≥ 28 kg. For
children who weigh between 20 and 28 kg, the 0.3
mg epinephrine autoinjector is recommended if the
patient is at high risk for severe anaphylaxis (asthma,
allergic to peanuts, tree nuts, or seafood) or has had a
previous episode of anaphylaxis. 138 Clinical reports
by the American Academy of Pediatrics Section on
Allergy and Immunology published in Pediatrics rec-
ommend prescribing the 0.15 mg autoinjector for chil-
dren weighing 10 kg to 25 kg and the 0.3 mg autoin-
jector to children weighing ≥ 25 kg.102,139 International
guidelines recommend using the 0.15 mg autoinjector
in children weighing 7.5 kg to 25 kg.12
Dosing for children weighing < 10 kg has been
challenging, with limited options. In 2017, the
FDA approved a 0.1 mg epinephrine autoinjector
with a shorter needle for use in infants and small
children weighing 7.5 kg to 15 kg.140 This prefilled
epinephrine autoinjector could potentially improve
outcomes for infants and small children experienc-
ing anaphylaxis. The alternative is to prescribe an
ampule of 1 mg/mL epinephrine with syringes and
have parents draw up the appropriate dose. One
study tested parents’ ability to do that and found
that parents were unable to reliably draw up the
correct dose.141 The authors of that study concluded
that, despite the fact that the pediatric epinephrine
autoinjector delivers too large a dose for infants, it
is preferable to dispensing ampules and syringes to
parents, as there is the potential for a much larger
dosing error with an ampule and syringe than with
the epinephrine autoinjector.
Injuries From Epinephrine Autoinjectors
Pediatric patient injuries from epinephrine auto-
injector use are relatively rare. A case series identi-
fied 22 epinephrine autoinjector-related injuries in
children.142 Cited complications were due to the
mode of injection in thrashing children and inappro-
priate needle retraction, including 18 needle lacera-
tions and 4 retained needles; 2 of the children with
retained needles required sedation for removal.142
A larger retrospective study found no systemic side
effects or long-term local complications from inad-
vertent digital epinephrine autoinjections.143
15 Copyright © 2019 EB Medicine. All rights reserved.
 Risk Management Pitfalls in the Management of Pediatric Anaphylaxis in
the Emergency Department
1. “My patient has wheezing and diffuse urti-
caria and flushing after eating a peanut butter
sandwich. He’s afraid of needles and he is not
hypotensive, so epinephrine is not necessary.
I’ll give an albuterol treatment and diphen-
hydramine and see if he improves.”
Delay in epinephrine treatment has been
identified as a risk factor for biphasic reactions
and fatal anaphylaxis. All guidelines emphasize
early treatment with epinephrine. Epinephrine
is the only first-line treatment for anaphylaxis.
Medications such as diphenhydramine may
be given as adjunctive treatments, but their
use should never delay or replace the use of
epinephrine.
2. “The patient doesn’t have cutaneous findings,
so it can’t be anaphylaxis.”
The diagnosis of anaphylaxis does not require
cutaneous findings. Acute onset of any 2 of
the systems listed in Table 2 (see page 4) or
hypotension after exposure to a known allergen
is sufficient for the diagnosis of anaphylaxis.
Even in cases of fatal anaphylaxis, patients may
lack cutaneous signs, so treatment should not be
delayed due to a lack of cutaneous findings.
3. “The epinephrine autoinjector is self-explan-
atory. I’m busy. He’ll figure it out if he ever
needs to use it.”
Clinicians frequently neglect to counsel patients
on appropriate epinephrine autoinjector use.
Many patients do not know how to use their
autoinjectors properly. Time spent teaching
a patient how to use the autoinjector may
be lifesaving during a future episode of
anaphylaxis.
4. “The nurse questioned my IM epinephrine
order because he’s always given epinephrine
subcutaneously.”
The onset of action of epinephrine is more rapid
with IM administration, and expert guidelines
recommend IM rather than subcutaneous
administration of epinephrine.
5. “Two patients just arrived with anaphylaxis.
They had both eaten fish at the same restaurant
tonight. Surely that’s just a coincidence.”
Scombroid poisoning presents with similar signs
and symptoms to those of anaphylaxis. It is
the likely diagnosis if multiple patients present
with anaphylaxis-like symptoms after eating the
same fish.
Copyright © 2019 EB Medicine. All rights reserved. 16
6. “This patient has a history of anaphylaxis
requiring intensive care unit admission. She
reported difficulty breathing after eating at a
restaurant, but that is probably due to anxiety,
since her only objective finding is urticaria.”
Subjective symptoms such as dyspnea may
be evidence of anaphylaxis and should not be
discounted, especially in patients with a history
of severe anaphylaxis.
7. “I won’t prescribe an epinephrine autoinjector be-
cause the patient will follow up with the pediatri-
cian tomorrow. The pediatrician can write for it.”
Even after observation in the ED, biphasic
reactions are possible after discharge. All
patients with anaphylaxis should be discharged
with an epinephrine autoinjector or with a
prescription for an autoinjector, as well as
education on how to use it.
8. “My 2-year-old patient had anaphylaxis, but he
only weighs 13 kg, so I can’t prescribe him an
epinephrine autoinjector.”
Clinical reports published by the American
Academy of Pediatrics recommend prescription
of the 0.15 mg autoinjector to otherwise healthy
children weighing between 10 kg and 25 kg.102,139
Alternatively, a 0.1 mg autoinjector has been
approved for use and can be prescribed, if available.
9. “The paramedics are calling for an order to
give epinephrine to a 5-year-old girl with a
history of bee sting anaphylaxis who now has
stridor, diffuse wheezing, and an oxygen satu-
ration of 92% after a bee sting. It sounds like
anaphylaxis, but I’d rather examine the patient
myself before giving any medications.”
Delayed epinephrine administration has been
associated with fatal and biphasic anaphylaxis.
Early administration of epinephrine decreases
the risk of morbidity and mortality from
anaphylaxis.54,60-62
10. “My patient had an anaphylactic reaction with
syncope, urticaria, and shortness of breath at home.
The mother gave the boy epinephrine, and his
symptoms completely resolved before he arrived.
I’m not sure why they even came to the ED.”
There is a risk of biphasic reactions after
symptom resolution. Guidelines vary in
their recommendations, but all recommend
some period of observation. The patient will
also need a prescription for a replacement
epinephrine autoinjector.
Reprints: www.ebmedicine.net/pempissues
Education on Epinephrine Autoinjector Use
Multiple studies of anaphylaxis deaths have dem-
onstrated that only a minority of patients who were
prescribed an epinephrine autoinjector administered
it appropriately during their fatal reaction. Many
patients did not even have their autoinjector avail-
able at the time of the fatal reaction.63,64,66 In a clinic-
based study, most anaphylaxis patients and their
families were not able to correctly demonstrate the
use of an epinephrine autoinjector.100 Additionally,
most resident and attending physicians also could
not demonstrate appropriate use of an epinephrine
autoinjector.100
A survey of 29 attending pediatricians found
that only 17% demonstrated to the parents and
patients how to use an epinephrine autoinjector and
only 24% gave written information at the time of
prescription.100 As multiple epinephrine autoinjec-
tors are available and instructions for use vary by
manufacturer, patients must understand how to use
the device they will receive.
In general, devices have a safety cap that must
be removed and then, ensuring that the device is ori-
ented with the needle perpendicular to the patient’s
outer thigh, the device is pressed firmly into the
thigh and held for 3 to 10 seconds (depending on the
manufacturer instructions). For children who are un-
able to cooperate, the leg should be well restrained
during epinephrine administration. Training autoin-
jectors and online videos demonstrating proper use
are available from manufacturers.
Summary
Anaphylaxis can present with a variety of signs and
symptoms and is frequently underdiagnosed. Early
recognition and treatment of this potentially fatal
condition is vital. IM epinephrine is the cornerstone
of treatment; evidence for other treatment options is
lacking. Expert guidelines agree that antihistamines
and corticosteroids are second-line treatments and
should never replace or delay epinephrine adminis-
tration. Patients diagnosed with anaphylaxis should
be discharged with an epinephrine autoinjector
or a prescription for an epinephrine autoinjector
and given instructions and/or a demonstration on
how to use it, education on allergen avoidance, and
instructions to follow up with a specialist in allergy
and immunology.
Case Conclusions
The parents of the 3-year-old girl stated that the girl’s
previous anaphylactic reaction began with urticaria and
facial swelling that progressed, resulting in a critical care
admission for airway compromise due to angioedema.
You administered epinephrine 0.01 mg/kg IM for sus-
pected anaphylaxis and observed the patient in the ED
June 2019 • www.ebmedicine.net
for 4 hours. The girl had complete resolution of the facial
swelling and urticarial rash. You reviewed the signs and
symptoms of anaphylaxis with the parents, discussed
allergen avoidance, and demonstrated appropriate use of
an epinephrine autoinjector. You discharged the patient
with a prescription for 2 epinephrine autoinjectors and an
anaphylaxis action plan.
Upon further questioning, the 8-year-old boy told
you that he ate a cookie after school. You assumed it
contained an egg product. You administered epinephrine
0.01 mg/kg IM and nebulized albuterol/ipratropium
bromide combination treatments, as well as corticoste-
roids and diphenhydramine. The patient’s pulmonary
examination improved dramatically with good aeration,
minimal wheeze, and pulse oximetry of 99% on room air,
and his skin returned to normal color. The boy told you
that he felt much better. You observed the patient in the
ED for 6 hours with no recurrence of respiratory distress
or wheeze, and he had normal vital signs. You instructed
the family on the use of an epinephrine autoinjector and
provided them with an anaphylaxis action plan. The pa-
tient was discharged with 2 epinephrine autoinjectors and
continued treatment for an acute asthma exacerbation.
You arranged for follow-up with a specialist in allergy and
immunology.
You gave the 15-year-old boy three 20-mL/kg boluses
of normal saline and 3 doses of epinephrine (0.3 mg) IM 5
to 10 minutes apart for persistent hypotension. His vital
signs improved, with a heart rate of 120 beats/min and
a blood pressure of 90/54 mg Hg. You administered IV
corticosteroids and admitted him to the intensive care unit
for further management.
Time- and Cost-Effective Strategies
• Limit laboratory testing in patients with anaphy-
laxis. Anaphylaxis is a clinical diagnosis, and
laboratory testing is rarely helpful. Unless a spe-
cialist in allergy and immunology has requested
testing during an acute episode, laboratory test-
ing is not necessary.
• Admission is not necessary in all patients. Most
patients do not benefit from prolonged observa-
tion. Expert guidelines support a 4- to 6-hour ob-
servation period. Detailed discharge instructions
and discharge with an epinephrine autoinjector
and demonstration of its use are vital.
Risk Management Caveat: Consider admission for
patients with severe anaphylaxis, anaphylaxis that is
slow to respond to epinephrine, a requirement for a
second dose of epinephrine or fluid boluses, or risk
factors such as uncontrolled asthma. Ensure that
patients are able to fill their prescription for the epi-
nephrine autoinjector and are comfortable using it.
Consider admission if the family is unable to access
emergency medical services.
17 Copyright © 2019 EB Medicine. All rights reserved.
Key Points
• Anaphylaxis can present with a variety of signs
and symptoms. Consider the diagnosis even
in patients who do not present with the classic
symptoms of urticaria, angioedema, or wheez-
ing. Two studies found that approximately half
of patients meeting criteria for food-related ana-
phylaxis did not receive a discharge diagnosis of
anaphylaxis.2,3
• IM epinephrine is recommended as the first-line
treatment in all anaphylaxis treatment guide-
lines. Multiple studies have found that patients
diagnosed with anaphylaxis frequently do not
receive IM epinephrine by EMS providers or in
the ED. Patients also underuse their epinephrine
autoinjectors.100
• Antihistamines and corticosteroids are, at best,
second-line treatments for anaphylaxis. Anti-
histamines may be beneficial as a second-line
adjunct agent to treat cutaneous symptoms of
anaphylaxis, but they do not relieve airway
symptoms, shock, or hypotension. Corticoste-
roids appear to decrease the length of stay in
patients hospitalized for anaphylaxis. Benefits of
corticosteroids have not been demonstrated in
patients with less severe anaphylaxis. gic and anaphylactic events in the National Electronic Injury
• The observation period must be individual-
ized, but a 4- to 6-hour observation period is
supported by several expert guidelines. The
Resuscitation Council (UK) recommends at least
6 hours of observation for most patients.35 The
statement published by the National Institute of
Allergy and Infectious Diseases/Food Allergy
and Anaphylaxis Network with input from the
American College of Emergency Physicians and
the American Academy of Pediatrics states that
a 4- to 6-hour observation period is appropriate
for most patients.1 Longer observation periods
may be considered for patients with severe
reactions or with risk factors for biphasic or fatal
anaphylaxis. (See Table 8, page 14.)
• Patients diagnosed with anaphylaxis should
be discharged with an epinephrine autoinjec-
tor and instructions to follow up with an aller-
gist. They also should be counseled in trigger
avoidance. Many studies demonstrate a need
for improvement in ED discharge medications
and instructions for patients with anaphylaxis.
One study of food allergy showed that only 35%
of patients with food-related anaphylaxis were
given instructions to avoid the offending food.95
A survey of 29 attending pediatricians found
that only 17% demonstrated to the parents and
patients how to use an epinephrine autoinjector,
and only 24% gave written information at the
time of prescription.100
Copyright © 2019 EB Medicine. All rights reserved. 18
References
Evidence-based medicine requires a critical ap-
praisal of the literature based upon study methodol-
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equally robust. The findings of a large, prospective,
randomized, and blinded trial should carry more
weight than a case report.
To help the reader judge the strength of each
reference, pertinent information about the study is
included in bold type following the reference, where
available. In addition, the most informative referenc-
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your smartphone or visit
www.ebmedicine.net/P0619.
1. Which of the following is TRUE regarding the
diagnosis and treatment of anaphylaxis?
a. Studies have demonstrated that anaphylaxis
is overdiagnosed and overtreated by EMS
personnel and emergency clinicians.
b. Studies have demonstrated that anaphylaxis
is underrecognized in EDs but, when
diagnosed, is almost always treated
appropriately.
c. Studies have demonstrated that EMS
personnel overdiagnose and overtreat
anaphylaxis, but emergency clinicians
appropriately diagnose and treat
anaphylaxis.
d. Studies have demonstrated that EMS
personnel and emergency clinicians
undertreat anaphylaxis.
Reprints: www.ebmedicine.net/pempissues
2. Which of the following patients meets the
criteria for anaphylaxis?
a. A 10-year-old boy with a known peanut
allergy who has a blood pressure of 82/30
mm Hg after accidentally eating a dessert
containing peanuts at a party
b. A 14-year-old girl without known allergies
with isolated syncope after a bee sting
who is now asymptomatic with a normal
physical examination
c. A 9-month-old boy with diffuse urticaria
and pruritus but otherwise normal vital
signs and physical examination after eating
an egg for the first time
d. A 3-year-old girl with a history of atopic
dermatitis who presents with 2 days of
profuse rhinorrhea and cough and 2 hours
of noisy breathing and diffuse wheeze on
pulmonary examination
3. Which of the following diagnostic criteria for
anaphylaxis is CORRECT?
a. Cutaneous symptoms are required for the
diagnosis of anaphylaxis.
b. Signs and symptoms in 2 organ systems are
required for the diagnosis of anaphylaxis.
c. Isolated hypotension after exposure to a
known allergen for the patient is consistent
with anaphylaxis.
d. Histamine and tryptase levels are necessary
to rule out other etiologies.
4. Which of the following is TRUE regarding
biphasic reactions?
a. Early administration of antihistamines
decreases the risk of a biphasic reaction.
b. The need for a second dose of epinephrine is
a potential risk factor for a biphasic reaction.
c. Biphasic reactions occur in 30% of pediatric
patients with anaphylaxis.
d. Biphasic reactions most commonly occur > 6
hours after the initial reaction.
5. Which of the following is a risk factor for fatal
anaphylaxis?
a. Presence of cutaneous symptoms
b. History of asthma
c. Immediate epinephrine administration
d. Age 5 to 9 years
6. What is the likely diagnosis in 2 friends who
both present with flushing, vomiting, abdomi-
nal cramping, and pruritus after eating sushi
together?
a. Scombroid poisoning
b. Bacterial gastroenteritis
c. Familial anaphylaxis
d. Anaphylaxis in one and panic attack in the
other
June 2019 • www.ebmedicine.net
7. Which of the following medications is the
most important to administer immediately to a
patient with an anaphylactic reaction?
a. Diphenhydramine
b. Ranitidine
c. Methylprednisolone
d. Epinephrine
8. What route and dose of epinephrine is the
most appropriate initial treatment in a 30-kg
child with diffuse urticaria, stridor, and lip
swelling?
a. 0.5 mL nebulized racemic epinephrine
b. 0.3 mL 1 mg/1 mL epinephrine
administered subcutaneously in the upper
arm
c. 0.3 mL 1 mg/1 mL epinephrine
administered intramuscularly in the thigh
d. 3 mL 0.1 mg/1 mL epinephrine
administered intravenously
9. Which of the following is TRUE regarding IV
epinephrine for anaphylaxis?
a. If an IV line has been established,
IV epinephrine is preferred over IM
epinephrine for first-line therapy.
b. The 1 mg/1 mL concentration is
recommended for IV administration in
anaphylaxis.
c. Cardiac arrest is the only appropriate
indication for IV epinephrine.
d. IV epinephrine is indicated if multiple bolus
doses of IM epinephrine fail to reverse
hypotension or other severe signs.
10. Which of the following is TRUE regarding
fatal anaphylaxis?
a. Approximately 3% of anaphylaxis episodes
are fatal.
b. Most deaths from anaphylaxis occur within
4 hours of allergen exposure.
c. Antihistamine treatment has been
demonstrated to reduce the risk of death in
food-related anaphylaxis.
d. Delayed anaphylaxis deaths are most
commonly due to insect stings.
23 Copyright © 2019 EB Medicine. All rights reserved.
 CME Information
Date of Original Release: June 1, 2019. Date of most recent review: May 15, 2019. Termination
date: June 1, 2022.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical
Education (ACCME) to provide continuing medical education for physicians. This activity
has been planned and implemented in accordance with the accreditation requirements and
December 2018 policies of the ACCME.
Number 12
Volume 15,
ing
Attacks Involv Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA
Bioterrorism nts: Preparedness
Author P
FAAP, FACE Medicine,

PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the
son, MD, MPH, Emergency Sciences;
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Garth Meckl
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of Pediatrics,
Chief, Pediat
Medicine,
r, MD, FACEP
David M. Walkeric Emergency
Department
, FAAP

of Pediatrics,
AAP Accreditation: This continuing medical education activity has been reviewed by the
American Academy of Pediatrics and is acceptable for a maximum of 48 AAP credits per
n's
Professor Sanzari Childre sity
MD, FAAP Associate bia; Joseph M.
Alson S. Inaba, ency Medicine of British Colum ency nsack Univer
r University Pediatric Emerg Hospital, Hacke, Hackensack, NJ
, MD, FAAP Pediatric Emerg ani Medical Cente Division Head,Children's Hospital, l Center
Ari Cohen Kapiol Medica
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BC MHA
& Children;

year. These credits can be applied toward the AAP CME/CPD Award available to Fellows and
Chief of Pediatr chusetts General BC, Canad
a Wang, MD,
-Chief for Women University
of Pediatrics, School of Vancouver, Vincent J. of Pediatrics and
Editors-in Medicine, Massator in Pediatrics, Professor A. Burns r, MD, MHPE ics
d Professor
Medicine;
Division
ius, MD Hospital; Instruc l School, Boston, MA of Hawaii John lu, HI Joshua Nagle or of Pediatr Emergency ric Emergency
Ilene Claud Director,
Professor; Harvard Medica Medicine,
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Associate ,

Candidate Fellows of the American Academy of Pediatrics.

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Quality Improv , MD, FAAP, h, MD, FACEP and Emerg
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UT
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Jay D. Fisher ency Matar Josep l; Associate n r; Director
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Program, Harbo Clinical Profes Pediatrics, University ine Services,
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Center, Torran , FACEP , Medicine and Vegas School of Profes sor of Emerg nt Chair, Emerg ency Medici , MA , Dallas
Las of
zko, MD, MSCR of Nevada, , NV and Pediat
rics, Assista ine al, Boston Health
Children’s Hospit
Tim Horec
Medicine,
Las Vegas
FACEP, Pediatric Emerg
ency Medic nal Editor

AOA Accreditation: Pediatric Emergency Medicine Practice is eligible for up to 48 American

FAAP
Professor
of Clinical he-Hill, MD, ement, Pediat n,
ric
James Napra
wa, MD
Emergency
Internatio FACEP,
Associate David Geffen Marianne Gausc Quality Improv Physician, VISIT US AT ACEP s, MD, FAAP,
Medicine, S Medicine Divisioe of Attending Benioff Lara Zibner
Emergency UCLA; Core FAAP, FAEM r, Los Angeles Emergency Colleg tment USCF CA tric
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School of
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Senior Physic A
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cksonville,
Depar
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Hospital, Oaklan SCIENTIFIC ASSEMBLY ltant, Paedia
Honorary Consu ine, St. Mary's

Osteopathic Association Category 2-A or 2-B credit hours per year.

Faculty and County EMS ency Medicine and Medicine-Ja ency Medic
y-Harbor-UCL FL r, MD October Emerg 1-3, 2018al College Trust, tor
Angeles Countr, Torrance, CA Clinical Emerg Geffen School Jacksonville, Joshua Rocke Medical
MD Chief and Hospital Imperi
Medical Cente Pediatrics,
David
at UCLA; Clinica
l
Stephanie
Kennebeck,
University
of Associate ant Profes
sor BOOTH 1921 Nonclinical Instruc
London, UK; Medicine, Icahn
d of Medicine r-UCLA Medical Professor, rics, Director, Assist Emergency
Editorial Boar FAAP Faculty, Harbotment of Emergency
Associate
Cincin nati Depar
tment of Pediat of Pediatrics
and
Childre n's Medical
of Emergency ine at Mount Sinai,
l of Medic
Avner, MD, Cohen Schoo

Needs Assessment: The need for this educational activity was determined by a survey of
Jeffrey R. of Center, Depar Angeles, CA Cincinnati,
OH Medicine, York, New
Hyde
New York,
NY
Depar tment Los MS Center of New
Chairman,
Professor
of Clinical Medicine, anda, MD,
Anupam Kharbl Care Services y Editor
Pharmacolog
FAAP,
Pediatrics, Children's Gerardi, MD, Park, NY
Maimonides Michael J. Chief, Critica Clinics of BCPS
Pediatrics, yn, NY ent
FACEP, Presid sor of Emergency Hospitals and MN s, MD of r, PharmD,
Brooklyn, Brookl Children's Steven Roger University Aimee Mishle Medicine Pharmacist,

medical staff, including the editorial board of this publication; review of morbidity and mortality
Hospital of Profes Minneapolis, Professor,
Associate l of Medicine Minnesota, Associate
School of
Medicine, Emergency
Icahn Schoo Pediatric or – PGY2 acy

Tick-Borne Illnesses:
Steven Bin,
MD UCSF Medicine, Director, FAAP, FACEP Connecticut Medicine Program Direct
l Professor, Tommy Y.
Kim, MD, ic Emergency Children's Medicine
Pharm
Associate Clinicane; Medical Directo
r, at Mount Sinai; ine, Goryeb or of Pediatr Attending cticut Emergency Medical
School of Mediciency Medicine, UCSF Emergency
Medic Associate Profess ne, University of ian, Conne CT Maricopa

data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency
town Physic ency,
September 2018
Morris Medici r, Hartfo rd, Resid
Hospital, Emergency Medicine, ix, AZ
Pediatric Emergn's Hospital, San Children's NJ de School of Medical Cente Center, Phoen

Identification and Manageme

r, Morristown, California Riversi unity Hospital, er, MD
Benioff Childre Medical Cente Stroth r
Riverside Comm Medicine, Volume 15, Number 9
opher ency
CME Edito
nt
CA be, MD, PhD Christ Emerg
Francisco, of Emergency Professor, l , FAAP
FAAP, Sandip Godamand Patient Safety Officer, Department Associate and Medica ka, MD, FACEP

physicians.
Cantor, MD, Pediatrics,
Richard M. Chief Quality ng
Riverside, CA
Authors Medicine, ric Brian S. Skrain ant Professor,

in the Emergency Department

Pediatrics, Attendi ne, Director, Pediat r, Clinical Assist Emergency
FACEP Medicine Professor of Medici an, MD, MHS rics and Education; ne; Directo
of EmergencyChief, Emergency Melissa Langh ency Medici Medicine Depar tment
of
Professor n Physician of l of The King's sor of PediatBellis, MD, Emerg
Jennifer MPH tion; Icahn School of Oklahoma
State
rics; Sectio Children's Hospita System, Norfolk, VA Associate Profes Instructor, ship Medicine,
and Pediat ency Medic
ine; Medicine; Fellow DepartmentSimula Sinai, New
of Pediatrics, York, NY
sity Cente
r for Health
Pediatric Emergr, Upstate Poison Daughters
Health Emergency of Education, Yale
r University at Mount Section of EmergencyUniver Medicine, Tulsa, OK
Director, Directo ency Medicine, of Colorado, Aurora, COMD, FAAP

Target Audience: This enduring material is designed for emergency medicine physicians,
Medical Directo Children's an, MD Sciences,
Abstract Contro l Cente r, Golisano
se, NY
Ran D. Goldm
Professor,
Depar tment of Pediatrics,
bia;
Pediat ric Emerg Ee Tay,
University
Schoo l of Medici MD ne, New Adam E. Vella,
Associate
Profes sor of Emerg al
rics, and Medic
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Hospital, Syracu of British Columric Clinical Assistant Professor, ine, Pediat ric
University Haven, CT MedicRonald O. Perelman
r of Pediat Department
MD, FAAP Director, Pediat Children's Emergency Medicine, Clinical Education,
Directo l of
Steven Choi, y Officer and Assoc
iate Research Site Chief,ine, Icahn Schoo

physician assistants, nurse practitioners, and residents.

BC , MD
Tick-borne illnesses are increasing Emergency
Medicine, a Robert LutenPediat Bellevue
rics andHospitalofCenter, ency Medic Pediatric New Emergency Medicine,
Chief Qualit l Quality, Yale ine; uver, BC, Canad Emerg
New York,atNY Mount Sinai,
Dean for Clinica in prevalence and geographi Hospital, Vanco Professor,
Medicine,
University of Medicine
reach. Because the presentati le School of
Medic
, c MD, MBA Emergency Peer Reviewers
nville, FL York, NY
Medicine/Ya on of these illnesses is sometime
ent, Chief
Quality Officer Joseph Habboushe, of Emergency
Florida, Jackso
nonspecific, they can often
Vice Presid Health System
, s sor
Assistant Profes angone and Michael Gottlieb, MD, RDMS
be misdiagnosed, especially
Yale New Haven NYU/L

Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical decision-
early stages of illness. A detailed
, CT in the Medicine, al Cente rs, New Director of Emergency
New Haven Bellevue Medic MD Aware LLC Ultrasound, Department of
history with questions involv- Rush University Medical Emergency Medicine,
ing recent activities and travel York, NY; CEO, Center, Chicago, IL
and a
tion will help narrow the diagnosis. thorough physical examina-
Lise Nigrovic, MD, MPH

making based on the strongest clinical evidence; (2) cost-effectively diagnose and treat the
Associate Professor of Pediatrics
While some illnesses can be and Emergency Medicine,
diagnosed on clinical findings Medical School, Boston Children’s
Hospital, Boston, MA
Harvard
alone, others require confirma-
tory testing, which may take Prior to beginning this activity,

most critical ED presentations; and (3) describe the most common medicolegal pitfalls for
days to weeks to result. This see “Physician CME Information”
reviews the emergency departme issue on the back page.
nt presentation of 9 common
tick-borne illnesses and evidence-
based recommendations for
identification, testing, and
treatment. each topic covered.
Editors-in-Chief Ari Cohen, MD, FAAP
CME Objectives: Upon completion of this activity, you should be able to: (1) recognize atypical
presentations of anaphylaxis and identify risk factors for fatal anaphylaxis; (2) differentiate
Ilene Claudius, MD Chief of Pediatric Emergency Joseph Habboushe, MD,
MBA Robert Luten, MD
Associate Professor; Director, Medicine, Massachusetts General Assistant Professor of Emergency Adam E. Vella, MD, FAAP
Medicine, NYU/Langone and Professor, Pediatrics and
Process & Quality Improvement Hospital; Instructor in Pediatrics, Emergency Medicine, University Associate Professor of Emergency
Program, Harbor-UCLA Medical Harvard Medical School, Boston, Bellevue Medical Centers, of Medicine, Pediatrics, and Medical
New Florida, Jacksonville, FL

other disease entities with signs and symptoms similar to anaphylaxis; (3) administer first-
MA York, NY; CEO, MD Aware
Center, Torrance, CA LLC Education, Director of Pediatric
Jay D. Fisher, MD, FAAP Garth Meckler, MD, MSHS
Tim Horeczko, MD, MSCR, Clinical Professor of Pediatric Alson S. Inaba, MD, FAAP Emergency Medicine, Icahn
FACEP, Associate Professor of Pediatrics, School
and Pediatric Emergency Medicine of Medicine at Mount Sinai,
FAAP Emergency Medicine, University University of British Columbia; New
Specialist, Kapiolani Medical York, NY

line and/or second-line anaphylaxis treatment(s) according to recommendations in national

Associate Professor of Clinical of Nevada, Las Vegas School Center Division Head, Pediatric Emergency
of for Women & Children; Associate
Emergency Medicine, David Medicine, Las Vegas, NV Medicine, David M. Walker, MD, FACEP,
Geffen Professor of Pediatrics, University BC Children's Hospital, FAAP
School of Medicine, UCLA; Director, Pediatric Emergency
Core Marianne Gausche-Hill, MD, of Hawaii John A. Burns School Vancouver, BC, Canada
Faculty and Senior Physician, FACEP, of Medicine; Associate Director,
Los FAAP, FAEMS Medicine, Honolulu, HI Joshua Nagler, MD, MHPEd

Angeles County-Harbor-UCLA
Medical Director, Los Angeles
Medical Center, Torrance,
CA County EMS Agency; Professor
of
Editorial Board Clinical Emergency Medicine
and
Pediatrics, David Geffen School
guidelines; and (4) provide anticipatory discharge guidance and referral to appropriate follow-
Department of Emergency
Assistant Professor of Pediatrics Medicine,
Madeline Matar Joseph, and New York-Presbyterian/Queens,
MD, FACEP, Emergency Medicine, Harvard
FAAP Medical Flushing, NY
Professor of Emergency Medicine School; Fellowship Director,
Division Vincent J. Wang, MD, MHA

up care for patients with anaphylaxis.

Jeffrey R. Avner, MD, FAAP
Chairman, Department of
Pediatrics, Professor of Clinical
Pediatrics, Maimonides Children's
Hospital of Brooklyn, Brooklyn,
NY
of
Medicine at UCLA; EMS Fellowship
Director, Harbor-UCLA Medical
Center, Department of Emergency
Medicine, Los Angeles, CA
Michael J. Gerardi, MD, FAAP,
and Pediatrics, Chief and Medical
Director, Pediatric Emergency
Medicine Division, University
of Florida College of Medicine-
Jacksonville, Jacksonville,
FL
of Emergency Medicine, Boston
Children’s Hospital, Boston,
MA
James Naprawa, MD
Attending Physician, Emergency
Department USCF Benioff
Professor of Pediatrics and
Emergency Medicine; Division
Chief, Pediatric Emergency
Medicine, UT Southwestern
Medical Center; Director
of

Discussion of Investigational Information: As part of the journal, faculty may be presenting

Steven Bin, MD Stephanie Kennebeck, MD Children's Hospital, Oakland, Emergency Services, Children's
FACEP, President CA
Associate Clinical Professor, Associate Professor of Emergency Associate Professor, University Joshua Rocker, MD Health, Dallas, TX
UCSF of
School of Medicine; Medical Cincinnati Department of Pediatrics, Associate Chief and Medical
Pediatric Emergency Medicine,
Director, Medicine, Icahn School of
Medicine Cincinnati, OH Director, Assistant Professor
International Editor
UCSF at Mount Sinai; Director, Pediatric

investigational information about pharmaceutical products that is outside Food and Drug
Benioff Children's Hospital, San Emergency Medicine, Goryeb Anupam Kharbanda, MD, of Pediatrics and Emergency Lara Zibners, MD, FAAP, FACEP,
Francisco, CA MS Medicine, Cohen Children's MMed
Children's Hospital, Morristown Chief, Critical Care Services Medical
Richard M. Cantor, MD, FAAP, Medical Center, Morristown, Children's Hospitals and Clinics Center of New York, Donald Honorary Consultant, Paediatric
NJ of and
FACEP Minnesota, Minneapolis, MN Barbara Zucker School of Emergency Medicine, St. Mary's

Administration approved labeling. Information presented as part of this activity is intended

Sandip Godambe, MD, PhD
Professor of Emergency Medicine
Chief Quality and Patient Safety
and Pediatrics; Section Chief,
Officer, Professor of Pediatrics
Pediatric Emergency Medicine; and
Emergency Medicine, Attending
Medical Director, Upstate Poison
Medicine
at Hofstra/Northwell, New Hospital Imperial College Trust,
Tommy Y. Kim, MD, FAAP, Hyde
FACEP Park, NY London, UK; Nonclinical Instructor
Associate Professor of Pediatric of Emergency Medicine, Icahn
Steven Rogers, MD
Emergency Medicine, University School of Medicine at Mount
of

Physician, Children's Hospital
Control Center, Golisano Children's
King's Daughters Health System,
Hospital, Syracuse, NY Norfolk, VA
Steven Choi, MD, FAAP
Ran D. Goldman, MD
solely as continuing medical education and is not intended to promote off-label use of any
California Riverside School of Associate Professor, University Sinai,
of the Medicine, of New York, NY
Riverside Community Hospital, Connecticut School of Medicine,
Attending Emergency Medicine Pharmacology Editor
Department of Emergency Medicine,
Riverside, CA Physician, Connecticut Children's
Aimee Mishler, PharmD, BCPS

Assistant Vice President,
Montefiore Health System;
Director,
Montefiore Network Performance
Improvement; Executive Director,
Montefiore Institute for Performance
Professor, Department of Pediatrics, Melissa Langhan, MD,
University of British Columbia;
Research Director, Pediatric
Emergency Medicine, BC
Children's
Hospital, Vancouver, BC, Canada
MHS
Associate Professor of Pediatrics
and
Emergency Medicine; Fellowship
Director, Director of Education,
Pediatric Emergency Medicine,
Medical Center, Hartford, CT
Christopher Strother, MD
Assistant Professor, Emergency
Medicine, Pediatrics, and Medical
Education; Director, Undergraduate
pharmaceutical product.
Emergency Medicine Pharmacist,
Maricopa Medical Center,
Phoenix, AZ
CME Editor

Faculty Disclosure: It is the policy of EB Medicine to ensure objectivity, balance, independence,

Improvement; Associate Professor Yale and Emergency Department
University School of Medicine, Deborah R. Liu, MD
of Pediatrics, Albert Einstein New Simulation; Icahn School of
College Haven, CT Medicine Associate Professor of Pediatrics,
of Medicine, Bronx, NY at Mount Sinai, New York, NY Keck School of Medicine of
USC;
Division of Emergency Medicine,

transparency, and scientific rigor in all CME-sponsored educational activities. All faculty
Children's Hospital Los Angeles,
Los Angeles, CA

participating in the planning or implementation of a sponsored activity are expected to disclose to

the audience any relevant financial relationships and to assist in resolving any conflict of interest
that may arise from the relationship. Presenters must also make a meaningful disclosure to the
Critical topics coming soon in audience of their discussions of unlabeled or unapproved drugs or devices. In compliance with
all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to
complete a full disclosure statement. The information received is as follows: Dr. Santillanes, Dr.
Pediatric Emergency Medicine Bansal, Dr. Campbell, Dr. Mishler, Dr. Skrainka, Dr. Claudius, Dr. Horeczko, and their related
parties report no relevant financial interest or other relationship with the manufacturer(s) of
Practice.... any commercial product(s) discussed in this educational presentation. Dr. Nunez reported
the following: community equipment grant, Kaleo, Inc.
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