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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 Hospital; Instructor in Pediatrics, Specialist, Kapiolani Medical Center Division Head, Pediatric Emergency Vincent J. Wang, MD, MHA
Harvard Medical School, Boston, MA for Women & Children; Associate Medicine, BC Children's Hospital, Professor of Pediatrics and
Ilene Claudius, MD Professor of Pediatrics, University Vancouver, BC, Canada Emergency Medicine; Division
Associate Professor; Director, Jay D. Fisher, MD, FAAP, FACEP
of Hawaii John A. Burns School of Chief, Pediatric Emergency
Process & Quality Improvement Clinical Professor of Emergency Joshua Nagler, MD, MHPEd
Medicine, Honolulu, HI Medicine, UT Southwestern
Program, Harbor-UCLA Medical Medicine and Pediatrics, University Assistant Professor of Pediatrics
Medical Center; Director of
Center, Torrance, CA of Nevada, Las Vegas School of Madeline Matar Joseph, MD, FACEP, and Emergency Medicine, Harvard
Emergency Services, Children's
Medicine, Las Vegas, NV FAAP Medical School; Associate Division
Tim Horeczko, MD, MSCR, FACEP, Health, Dallas, TX
Professor of Emergency Medicine Chief and Fellowship Director, Division
FAAP Marianne Gausche-Hill, MD, FACEP,
Associate Professor of Clinical FAAP, FAEMS and Pediatrics, Assistant Chair, of Emergency Medicine, Boston International Editor
Pediatric Emergency Medicine Children’s Hospital, Boston, MA
Emergency Medicine, David Geffen Medical Director, Los Angeles Lara Zibners, MD, FAAP, FACEP,
Quality Improvement, Pediatric
School of Medicine, UCLA; Core County EMS Agency; Professor of James Naprawa, MD MMed
Emergency Medicine Division,
Faculty and Senior Physician, Los Clinical Emergency Medicine and Attending Physician, Emergency Honorary Consultant, Paediatric
University of Florida College of
Angeles County-Harbor-UCLA Pediatrics, David Geffen School Department USCF Benioff Emergency Medicine, St. Mary's
Medicine-Jacksonville,
Medical Center, Torrance, CA of Medicine at UCLA; Clinical Children's Hospital, Oakland, CA Hospital Imperial College Trust,
Jacksonville, FL
Faculty, Harbor-UCLA Medical London, UK; Nonclinical Instructor
Joshua Rocker, MD
Editorial Board Center, Department of Emergency Stephanie Kennebeck, MD Associate Chief and Medical of Emergency Medicine, Icahn
Jeffrey R. Avner, MD, FAAP Medicine, Los Angeles, CA Associate Pr ofessor, University of School of Medicine at Mount Sinai,
Director, Assistant Professor of
Chairman, Department of Cincinnati Department of Pediatrics, New York, NY
Michael J. Gerardi, MD, FAAP, Pediatrics and Emergency Medicine,
Pediatrics, Professor of Clinical Cincinnati, OH
FACEP, President Cohen Children's Medical Center of
Pediatrics, Maimonides Children's Associate Professor of Emergency Anupam Kharbanda, MD, MS New York, New Hyde Park, NY Pharmacology Editor
Hospital of Brooklyn, Brooklyn, NY Medicine, Icahn School of Medicine Chief, Critical Care Services Aimee Mishler, PharmD, BCPS
Steven Rogers, MD
Steven Bin, MD at Mount Sinai; Director, Pediatric Children's Hospitals and Clinics of Emergency Medicine Pharmacist,
Associate Professor, University of
Associate Clinical Professor, UCSF Emergency Medicine, Goryeb Minnesota, Minneapolis, MN Program Director – PGY2
Connecticut School of Medicine,
School of Medicine; Medical Director, Children's Hospital, Morristown Emergency Medicine Pharmacy
Tommy Y. Kim, MD, FAAP, FACEP Attending Emergency Medicine
Pediatric Emergency Medicine, UCSF Medical Center, Morristown, NJ Residency, Maricopa Medical
Associate Professor of Pediatric Physician, Connecticut Children's
Benioff Children's Hospital, San Center, Phoenix, AZ
Sandip Godambe, MD, PhD Emergency Medicine, University of Medical Center, Hartford, CT
Francisco, CA Chief Quality and Patient Safety Officer, California Riverside School of Medicine, CME Editor
Christopher Strother, MD
Richard M. Cantor, MD, FAAP, FACEP Professor of Pediatrics, Attending Riverside Community Hospital, Associate Professor, Emergency Brian S. Skrainka, MD, FACEP, FAAP
Professor of Emergency Medicine Physician of Emergency Medicine, Department of Emergency Medicine, Medicine, Pediatrics, and Medical Clinical Assistant Professor of
and Pediatrics; Section Chief, Children's Hospital of The King's Riverside, CA Education; Director, Pediatric Emergency Medicine, Oklahoma
Pediatric Emergency Medicine; Daughters Health System, Norfolk, VA Melissa Langhan, MD, MHS Emergency Medicine; Director, State University Center for Health
Medical Director, Upstate Poison Ran D. Goldman, MD Associate Professor of Pediatrics and Simulation; Icahn School of Medicine Sciences, The Children’s Hospital at
Control Center, Golisano Children's Professor, Department of Pediatrics, Emergency Medicine; Fellowship at Mount Sinai, New York, NY Saint Francis, Tulsa, OK
Hospital, Syracuse, NY University of British Columbia; Director, Director of Education, Adam E. Vella, MD, FAAP
Steven Choi, MD, FAAP Research Director, Pediatric Pediatric Emergency Medicine, Yale Director of Quality Assurance, APP Liaison
Chief Quality Officer and Associate Emergency Medicine, BC Children's University School of Medicine, New Pediatric Emergency Medicine, Brittany M. Newberry, PhD, MSN,
Dean for Clinical Quality, Yale Hospital, Vancouver, BC, Canada Haven, CT New York-Presbyterian, MPH, APRN, ENP-BC, FNP-BC
Medicine/Yale School of Medicine; Joseph Habboushe, MD, MBA Robert Luten, MD Weill Cornell, New York, NY Faculty, Emory University School
Vice President, Chief Quality Officer, Assistant Professor of Emergency Professor, Pediatrics and of Nursing, Emergency Nurse
David M. Walker, MD, FACEP, FAAP
Yale New Haven Health System, Medicine, NYU/Langone and Emergency Medicine, University of Practitioner Program, Atlanta, GA;
Chief, Pediatric Emergency
New Haven, CT Bellevue Medical Centers, New Florida, Jacksonville, FL Nurse Practitioner, Fannin Regional
Medicine, Department of Pediatrics,
Ari Cohen, MD, FAAP York, NY; CEO, MD Aware LLC Hospital Emergency Department,
Garth Meckler, MD, MSHS Joseph M. Sanzari Children's
Chief of Pediatric Emergency Blue Ridge, GA
Alson S. Inaba, MD, FAAP Associate Professor of Pediatrics, Hospital, Hackensack University
Medicine, Massachusetts General Pediatric Emergency Medicine University of British Columbia; Medical Center, Hackensack, NJ
Case Presentations gies and is not taking any medications. His vital signs
do not improve after a second 20-mL/kg bolus of normal
A 3-year-old girl with a known peanut allergy arrives to saline. You consider his diagnosis. Is this dehydration
your ED via EMS. The girl was given a cookie by a class- from acute gastroenteritis or food poisoning, or perhaps
mate and immediately developed a generalized urticarial an atypical presentation of anaphylaxis? Are there any
rash. EMS personnel gave her 12.5 mg of oral diphen- labs that can help you decide if this is an anaphylactic
hydramine and transported her to the ED. On examina- reaction? You recall that patients with anaphylaxis can
tion, the patient has a heart rate of 160 beats/min with present with gastrointestinal and cardiovascular symp-
normal oxygenation and perfusion. She has bilateral peri- toms, with no skin changes. You decide to administer 0.3
orbital swelling, without respiratory distress, wheezing, mg of epinephrine IM. The boy's mental status and capil-
vomiting, or diarrhea. The accompanying daycare teacher lary refill time improve, but he is persistently hypotensive.
tells you that the girl has previously been admitted to the Should you administer another dose of epinephrine? What
intensive care unit for anaphylaxis. You call the girl's are the criteria for admission of a patient with anaphy-
parents for more information and wonder what to do in laxis?
the meantime. Is diphenhydramine sufficient treatment
for this patient? Are corticosteroids indicated? Is this just Introduction
an allergic reaction or could it be an anaphylactic reac-
tion? What are the criteria for diagnosis of anaphylaxis? An allergic reaction is an overreaction of the im-
What are the indications for administering epinephrine in mune system to a foreign substance (allergen). Ana-
patients with anaphylaxis? phylaxis is a type of an allergic reaction that is an
Your next patient is an 8-year-old boy with a history acute, severe systemic hypersensitivity reaction that
of moderate persistent asthma. He presented to the ED via can rapidly lead to death.1 The signs and symptoms
EMS for respiratory distress and wheezing. The patient of anaphylaxis are similar to other common illness-
was walking home from school when he began coughing es, which can make diagnosis challenging. Atypical
and felt short of breath. When he arrived home, he was anaphylaxis can be even more difficult to diagnose,
coughing persistently, wheezing, diaphoretic, and red in because some of the typical signs of anaphylaxis are
the face. On arrival to the ED, the patient is given inhaled not present. As such, many cases are misdiagnosed
nebulized albuterol via face mask and is afebrile with the and undertreated.2-7 Early treatment of anaphy-
following vital signs: oxygen saturation, 90% on oxygen; laxis with epinephrine can prevent progression
heart rate, 150 beats/min; respiratory rate, 38 breaths/min; to life-threatening respiratory failure and/or car-
and blood pressure, 135/80 mm Hg. He appears tired, has diovascular collapse.1,8-15 All published guidelines
moderate retractions with poor aeration on lung examina- recommend early administration of epinephrine for
tion, bounding pulses, and his skin appears diffusely red anaphylaxis, even in uncertain cases.1,11-18 Despite
and warm. He states he has an egg allergy. He previously this recommendation, studies suggest that epineph-
had a remote admission for an asthma exacerbation but has rine remains underutilized by emergency clinicians,
not had any surgeries. He had been in good health prior to and that gaps in knowledge of management of
today. You are concerned that this could be an anaphylac- anaphylaxis exist among primary care providers as
tic reaction. What is the best treatment for anaphylaxis? well.19,20 Furthermore, patients with anaphylaxis
How long should you observe the patient for a biphasic are often misdiagnosed with an “allergic reaction”
reaction or fatal anaphylaxis? and given antihistamines and corticosteroids instead
An otherwise healthy 15-year-old boy is brought to of epinephrine.2,5,7 Recent studies suggest that the
the ED by EMS for a syncopal episode at home. In the incidence of anaphylaxis is increasing globally,21-26
past 4 hours, he has had 4 episodes of nonbilious vomiting with an increase in both emergency department
and 3 episodes of watery, nonbloody diarrhea with crampy (ED) visits and hospitalizations. Pediatricians, first
abdominal pain. He has not had a fever. The boy’s parents responders, and emergency clinicians should there-
state that he was going to use the restroom after eating fore be well versed in the variety of presentations of
dinner, and he fell on his way to the bathroom. EMS anaphylaxis and remain vigilant.
administered a 20-mL/kg bolus of normal saline en route This issue of Pediatric Emergency Medicine Practice
to the ED. On arrival to the ED, the patient appears tired offers guidance on the identification of patients with
and is diaphoretic. His vital signs are as follows: oxygen anaphylaxis, including those with atypical presenta-
saturation, 99% on room air; heart rate, 150 beats/min; tions, reviews recent guidelines and evidence-based
respiratory rate, 22 breaths/min; blood pressure, 60/40 recommendations for first-line and second-line ana-
mm Hg, and temperature, normal. He is able to answer phylaxis treatment, describes risk factors associated
questions, has clear lungs, no abdominal tenderness, and with biphasic anaphylaxis and fatal anaphylaxis, and
a capillary refill time of 3 to 4 seconds. The boy appears discusses guidelines for patient disposition.
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-

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Critical Appraisal of the Literature Cochrane Database of Systematic Reviews yielded
several systematic reviews on anaphylaxis treatment
A literature review was performed using the and management: a 2007 review of H1 antihista-
PubMed and Ovid MEDLINE® databases with the mines in anaphylaxis,27 a 2009 review of epineph-
search terms anaphylaxis, allergic reaction, food allergy, rine,28 a 2012 review of epinephrine autoinjectors,29
drug allergy, anaphylactic shock, epinephrine, adrenaline, and a 2012 review of glucocorticoids.30
antihistamines, glucocorticoids, biphasic reaction, and The literature on pediatric anaphylaxis is
fatal anaphylaxis. Additionally, the references of each limited, and it is mostly extrapolated from adult
identified article were reviewed for relevant cita- studies, retrospective chart reviews, epidemiologic
tions. A total of 143 articles from 1985 to the present studies, review articles, and case reports. Most stud-
were chosen for inclusion. ies are retrospective, with associated limitations.
National and international organizations have Results are difficult to compare because there was
published guidelines for the diagnosis, manage- no standard definition for anaphylaxis until publi-
ment, and treatment of anaphylaxis.1,8-15 (See Table cation of consensus guidelines in 2006.1 (See Table
1.) In 2011, the World Allergy Organization released 2, page 4.) Reported incidence and outcomes vary
anaphylaxis guidelines that have since been updated greatly, likely due to the lack of a standard definition
with current evidence-based recommendations. In and variability in reporting. When available, studies
2014, both the International Consensus and the Joint restricted to pediatric patients were reviewed and
Task Force on Practice Parameters released updated included. However, most studies on anaphylaxis
anaphylaxis guidelines and practice parameters. A include all ages, so pediatric-specific data are not
search of the National Guideline Clearinghouse also always available, and many of the references in this
yielded a 2014 anaphylaxis guideline from the Euro- review involve combined pediatric and adult data.
pean Academy of Allergy and Clinical Immunology. Relevant adult-only studies were included when
Although there are multiple published guide- necessary to supplement limited pediatric data.
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 Title

2006 Symposium convened by the National Institute of Allergy and Infectious Second symposium on the definition and management of
Disease/Food Allergy and Anaphylaxis Network (13 participating anaphylaxis: summary report—second National Institute of
organizations, including the American College of Emergency Allergy and Infectious Disease/Food Allergy and Anaphylaxis
Physicians and the American Academy of Pediatrics) Network Symposium1

2011 World Allergy Organization (WAO) World Allergy Organization guidelines for the assessment and
management of anaphylaxis8
2012 2012 update9
2013 2013 update of the evidence base10
2015 2015 update of the evidence base11

2014 European Academy of Allergy and Clinical Immunology (EAACI) Anaphylaxis: guidelines from the European Academy of Allergy
Taskforce and Clinical Immunology12

2014 International Collaboration in Asthma, Allergy and Immunology International Consensus (ICON) document on anaphylaxis13
(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 Emergency department diagnosis and treatment of anaphylaxis:
Academy of Allergy, Asthma & Immunology; the American College a practice parameter15
of Allergy, Asthma & Immunology; and the Joint Council of Allergy,
2015 Asthma and Immunology (JCAAI) Anaphylaxis—a practice parameter update 201514

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Epidemiology College of Allergy, Asthma & Immunology Epidemi-
ology of Anaphylaxis Working Group estimated the
The incidence of anaphylaxis is unclear due to vari- lifetime prevalence of anaphylaxis from all causes to
ability in clinical presentation, recognition, report- be 0.05% to 2%.33 Anaphylaxis appears to be more
ing, etiology, diagnostic coding, study populations, common in children than adults and is likely under-
study designs, geographic variations, and data reported in the youngest patients.2,33-35 Anaphylaxis
sources. Studies based on self-reports or ED data in infants may be missed because symptoms of facial
may focus on severe reactions, underestimating the flushing, vomiting, and loose stool are nonspecific,
true incidence of anaphylaxis. In several studies, and these symptoms are easily attributed to other
approximately one-third to half of patients meeting diagnoses.35,36 After puberty, anaphylaxis appears to
criteria for food-related anaphylaxis did not receive a be more common in women than men.37 In contrast,
discharge diagnosis of anaphylaxis.2,3,31 studies in children show either a male predominance
In a 2014 survey of adults living in the United or no gender difference.7,23,38-40
States, 1.6% to 5.1% of respondents self-reported a Several studies in the United States have demon-
history of at least 1 lifetime episode of anaphylaxis.32 strated a significant increase in ED visits for anaphy-
A comprehensive literature review by the American 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-
Table 2. Clinical Criteria For Diagnosing tion for anaphylaxis in children also appears to be
Anaphylaxis rising. Lin et al found a 4-fold increase in anaphylaxis
Anaphylaxis is highly likely when any one of the following 3 hospitalizations from 1990-2006,23 and Rudders et al
criteria are fulfilled: found that admissions for food-induced anaphylaxis
1. Acute onset of an illness (minutes to several hours) with had doubled from 2000-2009.44
involvement of the skin, mucosal tissue, or both (eg,
generalized hives, pruritus or flushing, swollen lips-tongue- Biphasic Reactions
uvula) A biphasic reaction is the recurrence of anaphylactic
AND AT LEAST ONE OF THE FOLLOWING symptoms within 72 hours without re-exposure to
a. Respiratory compromise (eg, dyspnea, wheeze- the trigger. Reported rates of biphasic reactions in
bronchospasm, stridor, reduced PEF, hypoxemia)
patients with anaphylaxis vary from 3% to 20%.45-52
b. Reduced BP or associated symptoms of end-organ
This wide range can, in part, be explained by the va-
dysfunction (eg, hypotonia [collapse], syncope,
incontinence)
riety of definitions of anaphylaxis used in different
studies. Additionally, some studies included patients
2. Two or more of the following that occur rapidly after exposure to
who did not receive appropriate initial treatment
a likely allergen for that patient (minutes to several hours):
and some included patients with mild symptoms
a. Involvement of the skin-mucosal tissue (eg, generalized
hives, itch-flush, swollen lips-tongue-uvula)
not requiring intervention as having experienced
b. Respiratory compromise (eg, dyspnea, wheeze- biphasic reactions.
bronchospasm, stridor, reduced PEF, hypoxemia) Several studies have tried to determine risk factors
c. Reduced BP or associated symptoms (eg, hypotonia for a biphasic reaction. One study reported that no
[collapse], syncope, incontinence) biphasic reactions occurred in patients whose symp-
d. Persistent gastrointestinal symptoms (eg, crampy toms had completely resolved within 30 minutes of
abdominal pain, vomiting) initiation of treatment.45 In another study, all patients
3. Reduced BP after exposure to known allergen for that patient with a biphasic reaction had required a second dose
(minutes to several hours): of epinephrine or a fluid bolus during their initial
a. Infants and children: low systolic BP (age specific) or resuscitation.53 Several studies have identified the
greater than 30% decrease in systolic BP* need for higher total doses of epinephrine for symp-
b. Adults: systolic BP of less than 90 mm Hg or greater than tom resolution to be a risk factor for biphasic anaphy-
30% decrease from that person’s baseline
laxis.49,50,53 Another study found that patients with
biphasic reactions had a longer delay from the onset of
Abbreviations: BP, blood pressure; PEF, peak expiratory flow.
symptoms to epinephrine administration than patients
*Low systolic blood pressure for children is defined as < 70 mm Hg for
with uniphasic reactions.51,54 Two studies reported an
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.
increased risk in patients requiring inhaled beta-ago-
Reprinted from the Journal of Allergy and Clinical Immunology, nist treatment,50,52 and data from 27 studies found an
Volume 117, Issue 2, Hugh A. Sampson, Anne Muñoz-Furlong, increased risk in patients with unknown inciting trig-
Ronna L. Campbell, et al, Second symposium on the definition and gers and initial hypotension.51 Based on current data,
management of anaphylaxis: summary report—Second National the need for > 1 dose of epinephrine or a fluid bolus
Institute of Allergy and Infectious Disease/Food Allergy and (hypotension), slow response to epinephrine, a delay
Anaphylaxis Network Symposium, Pages 391-397, Copyright 2006, in epinephrine administration, need for treatment with
with permission from the American Academy of Allergy, Asthma & inhaled beta agonists, and an unknown inciting trigger
Immunology. https://www.jacionline.org/

Copyright © 2019 EB Medicine. All rights reserved. 4 Reprints: www.ebmedicine.net/pempissues


should be considered risk factors for biphasic reactions. Although a large number of patients with anaphy-
(See Table 3.) laxis demonstrate cutaneous symptoms, in 2 case series
of fatal anaphylaxis, < 15% of patients had cutaneous
Fatal Anaphylaxis symptoms.60,66 It is unclear if this was due to chance,
Despite the increase in prevalence and hospitalization if the lack of cutaneous symptoms is a marker for
rates for anaphylaxis,23,41,44 death due to anaphylaxis severe anaphylaxis, or if recognition of anaphylaxis
is rare (1 death per million people per year).22,25,26,42 and initiation of appropriate treatment was delayed
Studies of pediatric patients who present to an ED because urticaria was absent. Patients, families, and
with anaphylaxis have demonstrated a mortality rate clinicians must be aware that epinephrine is indicated
of < 1%.26,53,55 This is consistent with other studies for patients with findings of anaphylaxis other than cu-
of pediatric and adult populations, which have also taneous symptoms so that epinephrine is administered
found the rate of fatal anaphylaxis to be < 1%.25,37,56-58 promptly, as delays are associated with fatal anaphy-
In the United States, fatality from anaphylaxis is more laxis.
frequent in elderly patients26,59 and is more common- Death appears to be uncommon if epinephrine is
ly due to medications (59%) than food (7%).40 administered immediately, but it has been reported.
Risk factors for death from anaphylaxis are based Three of 48 patients in one series died despite appro-
on limited data but seem to vary according to etiology. priate self-administration of epinephrine.64 In another
Asthma and age appear to be risk factors for fatal food- case series, 2 of 32 deaths occurred in patients who had
related anaphylaxis.22,34,59-64 In one study, all 13 pediatric not responded to self-administered epinephrine.61
patients with fatal or near fatal food-related anaphylaxis
had asthma.60 Most food-related anaphylaxis deaths Etiology and Pathophysiology
seem to occur in adolescents and young adults.22,61,62
These patients are thought to be at higher risk at least in Anaphylaxis in children is most commonly due
part because they are less likely to avoid known triggers to food, possibly due to an increased incidence of
or carry epinephrine autoinjectors.65 Recent data on fatal food allergies in this age group.39,55,56 A review by
anaphylaxis indicate that a known allergen, lack of or Sicherer and Sampson revealed the rate of food
delayed use of epinephrine, peanut or tree-nut allergen, allergy in children to be near 8%, compared to 5%
and maintenance of an upright posture during symp- in adults.67 Recent studies have found an increase
toms are also factors associated with increased risk of in ED visits and hospitalizations for food-related
fatality in food-related anaphylaxis.22,40,59 Older age and anaphylaxis.7,24,41,44,68,69 Peanuts and tree nuts are the
underlying respiratory or cardiovascular disease have most common foods to cause anaphylaxis.7,55,56,70,71
been associated with increased risk for fatal drug-in- Vaccine-related anaphylaxis is very rare, with an in-
duced anaphylaxis, and cardiovascular disease has also cidence of about 1.5 cases per 1 million vaccinations
been described as a risk factor for fatal venom-induced administered.72 In contrast to the predominance of
anaphylaxis.59 (See Table 3.) food-related anaphylaxis in children, anaphylaxis in
adults is more likely to be triggered by medications,
Table 3. Risk Factors for Biphasic Reactions radiocontrast dye, or insect stings.40,59,66 Common
and Fatal Anaphylaxis causes of anaphylaxis are listed in Table 4.

Biphasic Reactions Table 4. Common Causes of Anaphylaxis


• The need for > 1 dose of epinephrine or a fluid bolus (hypotension)
• Slow response to epinephrine
Foods
• A delay in epinephrine administration
• Peanuts • Eggs
• The need for treatment with inhaled beta agonists
• Tree nuts • Sesame seeds/other sesame
• Unknown inciting trigger and initial hypotension
• Shellfish products
• Fish • Food additives
Fatal Anaphylaxis
• Milk
• Food-related anaphylaxis
Asthma
Medications
l

l Age, adolescent or young adult


• Antibiotics
l Known allergen
• Nonsteroidal anti-inflammatory drugs
l Absence or delayed use of epinephrine

Peanut or tree-nut allergy


Insects
l

l Maintenance of an upright posture during symptoms


• Hymenoptera (including bees, yellow jackets, wasps, and ants)
• Drug-induced anaphylaxis
Older age
Used with permission from EB Medicine, publisher of Pediatric
l

Underlying respiratory or cardiovascular disease


Emergency Medicine Practice, from: Genevieve Santillanes
l

• Venom-induced anaphylaxis and Joshua Davidson. An Evidence-Based Review of Pediatric


Cardiovascular disease
Anaphylaxis. Pediatric Emergency Medicine Practice. 2010;7(10):1-
l

www.ebmedicine.net 22. © 2010 EB Medicine.

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Immune-Mediated Hypersensitivity anaphylactoid reactions as well.75 The underly-
Immunoglobulin E (IgE) is central to the develop- ing mechanism for anaphylactoid reactions is not
ment of anaphylaxis. Upon exposure to an allergen, completely understood, but triggers appear to cir-
B cells become sensitized and produce allergen- cumvent the classic IgE-mediated pathway, directly
specific IgE. IgE binds to the Fc (fragment crystal- activating basophils and mast cells to release media-
lizable) epsilon R1 receptor found on basophils and tors.74,76 Some triggers cause anaphylaxis via both
mast cells. When an allergen binds to the IgE-mast the traditional IgE-mediated and direct activation
cell complex, the mast cell releases mediators of the pathways.34,77
anaphylactic response, including histamine, leukot-
rienes, and prostaglandins.34,73 Higher IgE levels Differential Diagnosis
increase the probability that a reaction will occur
with re-exposure to the antigen.74 Furthermore, IgE The differential diagnosis of anaphylaxis varies de-
increases expression of its own receptor on basophils pending on the patient’s presentation.78 (See Table 5.)
and mast cells, creating a positive feedback loop, re- Idiopathic or hereditary angioedema should be consid-
sulting in a more vigorous anaphylactic response.74 ered for patients with lip and tongue swelling. Various
causes of shock should be considered for patients with
Nonimmune-Mediated Hypersensitivity hypotension. The differential diagnosis of urticaria is
Triggers such as radiocontrast dye, intravenous broad. One unusual entity that may be considered in
N-acetylcysteine, ethanol, and opioids can induce the differential is cold-induced urticaria, a familial or
nonallergic anaphylactic (anaphylactoid) reactions.34 acquired disorder resulting in development of urticaria
A heparin contaminant has been reported to cause 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

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Scombroid Poisoning as needed for hypoxia, and intravenous (IV) fluids
Scombroid poisoning is easily misdiagnosed as should be given for hypotension or other evidence
anaphylaxis. Scombroid poisoning is thought to be of shock.13 Intramuscular (IM) epinephrine should
caused by high levels of histamine in poorly refriger- be administered as soon as possible in patients with
ated fish. Histidine, naturally present in the flesh of evidence of anaphylaxis.16,54,60-62 Epinephrine admin-
fish, is broken down by bacteria to histamine. Inad- istration is generally incorporated into paramedic
equate refrigeration accelerates this process. The fish advanced life support protocols. Small studies have
may not appear spoiled, and it can taste and smell demonstrated that emergency medical technicians
normal. Symptoms occur within minutes to hours of administered epinephrine to appropriate patients
consumption and may include a peppery taste in the and that administration by emergency medical tech-
mouth, burning or tingling of the oral mucosa, head- nicians was safe.87,88
ache, dizziness, flushing, sweating, rash, pruritus, Although paramedics are trained in adminis-
abdominal cramping, diarrhea, nausea, and vomit- tration of epinephrine, anaphylaxis is often under-
ing.79,80 Patients may have hypotension, tachycardia, recognized and undertreated by EMS personnel.
and circulatory collapse. Three pediatric studies found that < 30% of patients
The time course and symptoms of scombroid meeting criteria for anaphylaxis were administered
poisoning and anaphylaxis are very similar. Since epinephrine by EMS,5,89,90 with children aged < 10
seafood is a common cause of anaphylaxis, the years less likely to receive epinephrine appropri-
diagnosis is challenging. If > 1 person presents ately.90 One national survey study also found that
with anaphylactic-like symptoms after eating fish, while a large percentage of EMS providers correctly
scombroid poisoning is likely. Scombroid poisoning recognized classic anaphylaxis, only 2.9% correctly
should also be considered in patients with apparent identified atypical anaphylaxis.91 Only 46.2% of
anaphylaxis who have previously eaten the same EMS providers identified epinephrine as the initial
fish multiple times without any allergic symptoms. drug of choice for anaphylaxis, and 36.2% stated that
If there is any question whether symptoms are due there were contraindications to epinephrine admin-
to scombroid poisoning or anaphylaxis, referral to istration in anaphylactic shock.91
an allergist for testing is appropriate. Delay in the administration of epinephrine has
been associated with hypoxic-ischemic encephalopa-
Mastocytosis thy and fatal anaphylaxis.54,60,62 One study on fatal
Mastocytosis is a chronic disorder that can mimic or anaphylaxis showed that the median time to respi-
cause anaphylactic reactions. Cutaneous mastocyto- ratory or cardiac arrest was 30 minutes for foods,
sis is due to proliferation of mast cells in the skin.81 It 15 minutes for venom, and 5 minutes for iatrogenic
is characterized by reddish-brown macules, papules, reactions.63 In half of the fatalities in another study,
plaques, or blisters that develop urticaria in response death occurred within 60 minutes of exposure.66
to physical trauma. Systemic mastocytosis occurs Given the increasing incidence of anaphylaxis and
when mast cells proliferate in other tissues including the potential for rapid decompensation, early pre-
the bone marrow, liver, spleen, and lymph nodes.81 hospital treatment is critical.
Usual signs and symptoms of systemic mastocytosis
overlap with signs and symptoms of anaphylaxis. Emergency Department Evaluation
Flushing, pruritus, abdominal pain, diarrhea, dys-
pnea, and tachycardia are seen in both. Patients with History
recurrent, idiopathic anaphylaxis may in fact have After stabilization, the trigger for the anaphylactic
underlying mastocytosis.81 Systemic mastocytosis is event should be identified, if possible. Important
rare in children but might be considered with recur- information to obtain includes a list of all foods and
rent, otherwise unexplained anaphylaxis. Anaphy- medications consumed several hours before the
laxis can occur in patients with both cutaneous and reaction (symptoms can present within minutes to
systemic mastocytosis, and it has been reported in hours after exposure to a trigger60) and any possible
children with severe diffuse cutaneous mastocyto- insect stings or bites. Ask about any chronic medica-
sis.82 tions (eg, beta blockers) that might affect response to
treatment. Comorbid diseases such as asthma may
Prehospital Care affect the severity of the reaction and disposition
decisions. Ask about any previous allergic reactions.
Anaphylaxis is an uncommon reason for emer- Patients with a previous anaphylactic reaction may
gency medical services (EMS) transport, with a chief have self-administered epinephrine before arrival
complaint of allergy or anaphylaxis accounting for to the ED; if this is the case, ask about the timing of
only 0.2% to 0.5% of EMS calls.83-86 Prehospital care administration and the response to the medication.
should focus on the ABCs (airway, breathing, and cir-
culation). Supplemental oxygen should be supplied

June 2019 • www.ebmedicine.net 7 Copyright © 2019 EB Medicine. All rights reserved.


Physical Examination Treatment
Anaphylaxis is an acute systemic reaction that usually
affects 2 or more organ systems. Initial symptoms may Epinephrine
be mild but can rapidly progress to a severe, life-threat- Epinephrine is the most important medication in
ening reaction. The most common signs and symptoms the treatment of anaphylaxis, as it has multiple
of an anaphylactic reaction are dermatologic and respi- potential benefits. Epinephrine increases peripheral
ratory.38 All patients with possible anaphylaxis should vascular resistance and has positive chronotropic
immediately have their vital signs checked, with and inotropic cardiac effects, thereby treating
particular attention paid to blood pressure and oxygen anaphylaxis-associated hypotension. Peripheral
saturation. The general assessment should focus on vasoconstriction reduces flushing, urticaria,
signs of altered mental status, shock, and respiratory and angioedema, and beta-adrenergic effects of
distress. Signs of airway obstruction, including stridor, epinephrine treat associated bronchospasm.18 In
wheezing, and decreased air movement, may be noted. addition to the immediate cardiorespiratory effects,
Airway patency and the patient’s ability to protect the epinephrine is thought to decrease further release of
airway should be assessed. Evidence of posterior oro- inflammatory mediators from basophils and mast
pharyngeal swelling should raise concern for impend- cells, and may play a role in preventing biphasic or
ing airway obstruction. late reactions.18,93
Most patients present with mucocutaneous symp- While epinephrine is clinically considered
toms such as urticaria, flushing, or angioedema.46,56 beneficial in the treatment of anaphylaxis, a rigorous
A minority of patients lack cutaneous manifesta- evidence base is lacking. A Cochrane review of the
tions.37,38,46,56,66 Patients may present with predomi- use of epinephrine in anaphylaxis found no random-
nantly gastrointestinal or neurologic symptoms (eg, ized or quasi-randomized trials.28 Since epinephrine
syncope or dizziness due to hypotension). For patients is accepted as effective, and untreated anaphylaxis is
who are unable to provide a history, examine the skin potentially fatal, a randomized controlled trial com-
for signs of an insect sting or bite, which may be the paring epinephrine and a placebo cannot be justified
trigger for the reaction. Reddish-brown papules or ethically. However, there is indirect evidence that
macules that become raised, red, and itchy after strok- epinephrine is effective in the treatment of anaphy-
ing may be indicative of mastocytosis. laxis. Early treatment with epinephrine before ED
Infants represent a significantly vulnerable arrival has been associated with decreased length
population since they are unable to describe the sub- of stay in the ED,94 lower risk of hospitalization,94
jective symptoms used to diagnose anaphylaxis.1,36 and a reduced risk of requiring multiple doses of
Age-appropriate criteria should be used to assess for epinephrine.43 Delayed administration of epineph-
tachycardia and hypotension in pediatric patients.8 rine has been associated with fatal and biphasic
anaphylaxis.54,60 In a study of fatal anaphylaxis in
Atypical Anaphylaxis children, all 6 children with fatal anaphylaxis had a
The wide range of potential signs and symptoms can significant delay from the time of allergen exposure
make the diagnosis of atypical anaphylaxis chal- to administration of epinephrine.60 The vast majority
lenging.1,8 When anaphylaxis occurs without skin of patients described in 2 series of fatal anaphylaxis
findings, it may not be recognized initially, delay- did not receive early epinephrine.61,62
ing diagnosis and treatment. In a postmortem case Despite being the recommended first-line treat-
review of fatal anaphylaxis, only 4 of 25 patients had ment, epinephrine is often underused. Retrospective
cutaneous findings (pruritus, urticaria, flushing).66 studies of ED treatment of anaphylaxis in adults and
Patients with anaphylaxis can present with symp- children have found rates of epinephrine adminis-
toms not meeting the full criteria for anaphylaxis, or tration ranging from 12% to 67%.37,39,95-97 A study of
have mild symptoms, and yet require administration the European Anaphylaxis Registry found that while
of epinephrine.15 Severe symptoms in a single organ ED epinephrine administration increased from 12%
system, or mild symptoms in a person with a known to 24% over the study period, the majority of pa-
allergen exposure and a previous history of anaphy- tients did not receive epinephrine.98 Multiple studies
laxis, can also represent anaphylaxis.14,15,92 Prompt have found that patients diagnosed with anaphy-
recognition and treatment with epinephrine, even in laxis are much more likely to receive corticoste-
uncertain cases, may prevent rapid progression to roids and antihistamines than epinephrine.2,5,95,96,99
respiratory or cardiovascular arrest.14 Furthermore, one pediatric study found that the
majority of ED epinephrine doses were incorrectly
Diagnostic Studies administered subcutaneously rather than IM.99
Not only is epinephrine underused in the ED set-
Anaphylaxis is a clinical diagnosis. Since anaphy- ting, but patients themselves underuse their epineph-
laxis must be treated immediately, laboratory tests rine autoinjectors. One study found that, although
are not helpful in ED management. 86% of pediatric patients stated they carried their

Copyright © 2019 EB Medicine. All rights reserved. 8 Reprints: www.ebmedicine.net/pempissues


epinephrine autoinjector at all times, only 55% carried or hypotension that led to epinephrine administra-
an unexpired injector at their allergy clinic visit.100 A tion, epinephrine overdose does have the potential
large longitudinal pediatric study found that among to cause serious harm. In one case, a 13-year-old girl
patients who did carry an epinephrine autoinjector at developed fatal pulmonary edema after IV admin-
the time of anaphylactic symptom development, only istration of 3.5 mg of epinephrine.63 Another case
50% of them used it before ED arrival.43 Similarly, report described a 5-year-old boy who developed
Ben-Shoshan et al found that among patients with ventricular dysrhythmias and myocardial ischemia
moderate to severe anaphylaxis who had an epineph- after receiving a 10-fold overdose of subcutaneous
rine autoinjector at the time of symptom develop- epinephrine.107 A case of takotsubo cardiomyopathy
ment, 33% did not use it.101 Parents of patients in has also been reported in a 24-year-old woman after
that study stated they either “panicked, had a fear of an overdose of IM epinephrine.108
needles, or were hesitant to use it.”101 Reasons for dosing errors are likely multifacto-
rial. The 1 mg/mL concentration of epinephrine is
Intramuscular Epinephrine less familiar than the 0.1 mg/mL concentration. A
All guidelines recommend early treatment of ana- concept paper published in the Annals of Emergency
phylaxis with IM epinephrine.1,12-18 There are no Medicine recommends that EDs add easy-to-read
absolute contraindications to the administration of labels to epinephrine syringes to distinguish IM
epinephrine in the setting of anaphylaxis.15 Pediatric and IV preparations in order to avoid inadvertent
dosing is 0.01 mg/kg of the 1 mg/mL concentration IV administration of concentrated epinephrine.105
administered IM, to a maximum of 0.5 mg.102 IM Expression of the concentration as a ratio (1:1000)
administration of epinephrine results in more rapid can be confusing because clinicians are more accus-
achievement of peak plasma epinephrine levels than tomed to mass concentrations (1 mg/mL). One study
subcutaneously administered epinephrine.103,104 found that clinicians took longer to calculate doses
Data in adults support the administration of epi- and were more likely to give an incorrect dose when
nephrine in the upper vastus lateralis muscle.104 Ad- calculating doses using ratios rather than mass con-
ministering the appropriate epinephrine autoinjector centrations.110 Additionally, calculation of weight-
dosing (0.1 mg, 0.15 mg, or 0.3 mg) is also an option. based pediatric doses introduces additional potential
errors; computerized emergency dosing calculators
Intravenous Epinephrine may decrease dosing errors.111,112
Most cases of anaphylaxis respond to IM epinephrine,
which is the safest route of administration in general. Antihistamines
However, in cases of hypotension refractory to repeat- Antihistamines are commonly recommended for
ed doses of IM epinephrine, the IV route may be con- the treatment of anaphylaxis.1,16,113,114 However, a
sidered. Evidence-based IV dosing recommendations Cochrane review of H1-receptor blockers in anaphy-
are not available, and recommended doses vary. The laxis did not identify any randomized or quasi-ran-
report from the Second Symposium on the Definition domized trials to support this statement.27 A system-
and Management of Anaphylaxis recommends bolus atic review of H2-receptor blockers in anaphylaxis
doses of 0.2 mcg/kg to a maximum of 10 mcg for yielded similar results.115 Antihistamines are consid-
persistent hypotension.1 The Resuscitation Council ered a second-line treatment and should never delay
(UK) guidelines give the option of IV bolus doses of 1 or replace epinephrine administration.
mcg/kg of 0.1 mg/mL epinephrine to a maximum of A study of ED patients with allergic reactions
50 mcg of IV epinephrine in cases requiring repeated found that those who received an H1 antihistamine
IM doses of epinephrine.16 Other experts recommend had a lower likelihood of progression to anaphylax-
epinephrine infusions rather than bolus doses.34 is.116 Studies in adults demonstrate that the combi-
nation of H1- and H2-receptor blockers is superior
Epinephrine Dosing Errors to an H1-receptor blocker alone in the treatment of
Multiple case reports describe epinephrine dosing cutaneous symptoms of mild allergic reactions.117,118
errors in patients with anaphylaxis, including inad- Antihistamines do not relieve respiratory compro-
vertent IV administration of the 1 mg/1 mL formu- mise, shock, or hypotension, but may be useful as
lation or IV administration of cardiac-arrest dosing a second-line agent to treat cutaneous symptoms of
of epinephrine.63,105-108 One study demonstrated that anaphylaxis. Additionally, administration of an-
the risk of overdose with IV bolus epinephrine was tihistamines before IV radiocontrast may prevent
61 times greater than with IM epinephrine.109 Seri- anaphylactoid reactions.119,120 There is no evidence
ous outcomes after epinephrine overdose in chil- to guide duration of treatment and expert guideline
dren and young adults without underlying cardiac recommendations vary.1,8,15,16,113,121 (See Table 6,
disease are unusual but have been described in case page 12.)
reports. While it is unknown if reported complica-
tions are due to epinephrine overdose or the hypoxia

June 2019 • www.ebmedicine.net 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 size that corticosteroids are an optional or second-
Anaphylaxis guidelines recommend treatment with line treatment for anaphylaxis and should never
corticosteroids as second-line therapy for patients delay or replace the administration of epinephrine.
with anaphylaxis, despite a lack of strong support- There is no evidence to guide the duration of cortico-
ing evidence.1,16,113,121 Corticosteroids have a slow steroid therapy.1,16,113,121 (See Table 7, page 13.)
onset of action and are not effective in the immediate For more information on corticosteroids as treat-
management of acute anaphylaxis. Corticosteroids ment for anaphylaxis, see the March 2018 issue of Pe-
are theorized to prevent biphasic or protracted diatric Emergency Medicine Practice, “Corticosteroid Use
reactions. However, a Cochrane review of gluco- in Management of Pediatric Emergency Conditions,”
corticoids for the treatment of anaphylaxis did not available at: www.ebmedicine.net/corticosteroids.
identify any randomized controlled trials (in adults
or children) to support this statement.30 Two retro- Airway Management
spective studies found that similar proportions of A literature search did not find any studies of
pediatric patients with biphasic and uniphasic reac- airway management in ED patients (adults or
tions received corticosteroids, but administration of children) with anaphylaxis. Recommendations
corticosteroids did not appear to protect against the from the Joint Task Force guidelines on anaphylaxis
development of biphasic reactions.53,54 A prospec- include preparing for airway management, includ-
tive study of patients with biphasic reactions found ing intubation if necessary, if there are any signs of
a statistically insignificant trend toward a decreased airway edema or associated respiratory compro-
incidence of biphasic reaction in patients receiv- mise.15 Clinicians must rely on their best judgment
ing corticosteroids.45 These were studies with small in airway management. Airway edema may worsen
numbers of patients with biphasic reactions. Larger if anaphylaxis is progressive despite appropriate
prospective studies are needed to determine if corti- treatment, and early intubation may be beneficial.
costeroid use alters the risk of developing a biphasic Patients with mucosal edema should be considered
reaction. to have difficult airways, and paralytics should be
A large retrospective study of children hospi- used with caution in these patients. Upper air-
talized with anaphylaxis found that early admin- way edema can significantly hinder mask rescue
istration of glucocorticoids was associated with a ventilation. Management of the difficult airway is
decreased length of stay, as well as a reduction in beyond the scope of this review, but alternatives to
recurrent epinephrine administration, supporting traditional orotracheal intubation (eg, a fiber optic
the use of glucocorticoids in pediatric patients who laryngoscope and a cricothyrotomy kit) should be
are hospitalized with anaphylaxis.122 available if tracheal intubation is attempted.
As with antihistamines, all guidelines empha-

Table 6. Expert Guideline Recommendations on Antihistamines for Treatment of Anaphylaxis


Organization Recommendations for H1-Receptor Recommendations for H2-Receptor
Blockers Blockers

Joint Task Force representing the American Academy of • Considered second-line • Considered second-line
Allergy, Asthma & Immunology; the American College • Diphenhydramine 1-2 mg/kg to 50 mg • Ranitidine 1 mg/kg to 50 mg IV
of Allergy, Asthma & Immunology; and the Joint Council parenterally, slow infusion
of Allergy, Asthma and Immunology15,121

National Institute of Allergy and Infectious Diseases, • Second-line treatment • Second-line treatment
Food Allergy and Anaphylaxis Network,1 and World • Diphenhydramine 1-2 mg/kg to 50 mg • Ranitidine 1 mg/kg to 50 mg either IV or
Allergy Organization8 parenterally or PO in mild cases PO in mild cases

European Academy of Allergology and Clinical • Recommended options: • Not adequately tested in children
Immunology113 chlorpheniramine, cetirizine,
levocetirizine, loratadine, desloratadine,
or fexofenadine

Resuscitation Council (UK)16 • 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

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 Reprints: www.ebmedicine.net/pempissues


Special Circumstances Exercise-Induced Anaphylaxis
Exercise-induced anaphylaxis occurs only during ex-
Beta Blockers ercise.130 Another variant, food-dependent exercise-
Epinephrine increases cyclic adenosine monophos- induced anaphylaxis, occurs during exercise only
phate (cAMP) through beta-adrenergic stimulation, after eating certain foods normally tolerated by the
and this pathway is less effective in patients taking patient.131 Wheat has been the most commonly im-
beta blockers. Case reports have been published plicated cause of food-dependent exercise-induced
that describe patients taking beta blockers who had anaphylaxis, but multiple foods may be causative.
unusually severe or treatment-refractory anaphylax- Emergent treatment for exercise-induced anaphy-
is.123 Two retrospective case-control studies demon- laxis is the same as for other forms of anaphylaxis.
strated an increased risk of moderate or severe ana-
phylactoid reactions after radiocontrast exposure in Controversies and Cutting Edge
patients taking beta blockers.124,125 However, a study
of ED patients demonstrated that patients taking Alternate Routes of Epinephrine Administration
beta blockers did not require more doses of epineph- In 2017 the FDA approved a 0.1 mg epinephrine autoin-
rine compared to those not taking beta blockers.126 jector with a shorter needle for use in infants and small
Glucagon has been proposed as a treatment for children weighing 7.5 to 15 kg. For more information, see
epinephrine-resistant anaphylactic shock in patients the "Epinephrine Autoinjector Doses" section, page 15.
taking beta blockers because glucagon increases
cAMP via alternate pathways and has chronotropic Vasopressin
and inotropic effects that are unaffected by beta
Most cases of pediatric anaphylaxis respond well
blockers.127 Several case reports describe patients
to epinephrine and IV fluids. The evidence base for
taking beta blockers who developed radiocontrast-
treatment of epinephrine-resistant anaphylaxis is
induced hypotension that was refractory to usual
lacking. There are multiple adult case reports of suc-
treatment, but whose hypotension was reversed
cessful use of vasopressin in patients with anaphy-
after glucagon administration.128,129
laxis that is resistant to usual treatment.132,133 The
Sufficient evidence is not available to change
dose administered in most case reports ranged from
recommendations for treatment of anaphylaxis in
2 to 10 international units, given as an IV bolus dose.
patients taking beta blockers. To our knowledge, use
No guidelines incorporate the use of vasopressin
of glucagon in anaphylaxis or an anaphylactoid reac-
for treatment of anaphylaxis in children, and, at this
tion has never been described in a pediatric patient.
time, there are no dosing recommendations. While
However, in patients failing usual treatment, glu-
further research is needed, vasopressin is an option
cagon may be considered. One practice parameter
for patients with anaphylaxis that is refractory to
recommends a pediatric dose of 20 to 30 mcg/kg, to
epinephrine and IV fluids.
a maximum dose of 1 mg.121

Table 7. Expert Guideline Recommendations on Corticosteroids for Treatment of Anaphylaxis


Organization Recommendations
Joint Task Force representing the American Academy of Allergy, Asthma Consider for patients with a history of idiopathic anaphylaxis or asthma
& Immunology; the American College of Allergy, Asthma & Immunology; and patients with severe or prolonged symptoms:
and the Joint Council of Allergy, Asthma and Immunology121 • Glucocorticosteroids 1-2 mg/kg/day IV, given every 6 hours
• For less critical patients: prednisone 0.5 mg/kg PO
National Institute of Allergy and Infectious Diseases, Food Allergy and Options:
Anaphylaxis Network1 • Methylprednisolone 1-2 mg/kg/dose IV, given every 6 hours
or
• Prednisone 1 mg/kg PO for milder attacks

European Academy of Allergology and Clinical Immunology113 • Not considered first-line


• Methylprednisolone or hydrocortisone as IV options

Resuscitation Council (UK)16 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

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 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 (FDA)-approved drug labels for autoinjectors state
reliability.1,8,12,13,15,16 (See Table 8, page 14.) Admis- that the 0.15 mg dose should be used for children
sion to an intensive care unit is indicated for patients weighing > 15 kg and < 30 kg, and the 0.3 mg dose
with treatment-resistant anaphylaxis. should be used for children weighing ≥ 30 kg. How-
ever, this would result in a significant underdose in
Discharge Medications and Referrals children weighing close to 30 kg. Children receiving
Many studies demonstrate a need for improvement larger doses of epinephrine experience more side
in ED discharge medications and instructions for pa- effects from the medication,137 but given the risks of
tients with anaphylaxis. One study of patients with undertreated anaphylaxis, a small overdose may be
food allergies showed that only 35% of patients with preferable to an underdose. One expert review states
food-related anaphylaxis were given instructions to that most allergists dispense the 0.15 mg autoinjec-
avoid the offending food.95 In the United States, 22% tor to children who weigh 10 kg to 20 kg and the 0.3
to 63% of patients diagnosed with anaphylaxis were mg autoinjector to children who weigh ≥ 28 kg. For
discharged with an epinephrine autoinjector and children who weigh between 20 and 28 kg, the 0.3
13% to 33% were referred to an allergist.70,95,96,99 An mg epinephrine autoinjector is recommended if the
Australian study found that only 17.5% of pediatric patient is at high risk for severe anaphylaxis (asthma,
patients with anaphylaxis were discharged with a allergic to peanuts, tree nuts, or seafood) or has had a
prescription for an epinephrine autoinjector, but 54% previous episode of anaphylaxis. 138 Clinical reports
of children were discharged with a prescription for by the American Academy of Pediatrics Section on
an H1-receptor blocker, and 28% were discharged Allergy and Immunology published in Pediatrics rec-
with a prescription for steroids.39 ommend prescribing the 0.15 mg autoinjector for chil-
Guidelines recommend prescribing an epineph- dren weighing 10 kg to 25 kg and the 0.3 mg autoin-
rine autoinjector and offering training on how to jector to children weighing ≥ 25 kg.102,139 International
use it, providing instructions on avoidance of the guidelines recommend using the 0.15 mg autoinjector
offending allergen (if known), and referring the in children weighing 7.5 kg to 25 kg.12
patient to a specialist in allergy and immunology on Dosing for children weighing < 10 kg has been
discharge from the ED. Additionally, since there is a challenging, with limited options. In 2017, the
small risk of recurrent symptoms after discharge, the FDA approved a 0.1 mg epinephrine autoinjector
child should be discharged to a reliable adult who is with a shorter needle for use in infants and small
able to administer the epinephrine autoinjector and children weighing 7.5 kg to 15 kg.140 This prefilled
access emergency services in case of a biphasic reac- epinephrine autoinjector could potentially improve
tion. outcomes for infants and small children experienc-
ing anaphylaxis. The alternative is to prescribe an
Epinephrine Autoinjector Doses ampule of 1 mg/mL epinephrine with syringes and
Until recently, epinephrine autoinjectors have been have parents draw up the appropriate dose. One
available in 2 doses in the United States, 0.15 mg and study tested parents’ ability to do that and found
0.3 mg. United States Food and Drug Administration 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
Figure 1. Time to Cardiac Arrest Following autoinjector delivers too large a dose for infants, it
Exposure to Triggering Agent 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
Richard SH Pumphrey. Fatal Anaphylaxis in the UK, 1992–2001. effects or long-term local complications from inad-
Anaphylaxis: Novartis Foundation Symposium 257, Volume vertent digital epinephrine autoinjections.143
257. Pages 116-132. Copyright Novartis Foundation, 2004, with
Permission from John Wiley and Sons.

June 2019 • www.ebmedicine.net 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- 6. “This patient has a history of anaphylaxis
caria and flushing after eating a peanut butter requiring intensive care unit admission. She
sandwich. He’s afraid of needles and he is not reported difficulty breathing after eating at a
hypotensive, so epinephrine is not necessary. restaurant, but that is probably due to anxiety,
I’ll give an albuterol treatment and diphen- since her only objective finding is urticaria.”
hydramine and see if he improves.” Subjective symptoms such as dyspnea may
Delay in epinephrine treatment has been be evidence of anaphylaxis and should not be
identified as a risk factor for biphasic reactions discounted, especially in patients with a history
and fatal anaphylaxis. All guidelines emphasize of severe anaphylaxis.
early treatment with epinephrine. Epinephrine
is the only first-line treatment for anaphylaxis. 7. “I won’t prescribe an epinephrine autoinjector be-
Medications such as diphenhydramine may cause the patient will follow up with the pediatri-
be given as adjunctive treatments, but their cian tomorrow. The pediatrician can write for it.”
use should never delay or replace the use of Even after observation in the ED, biphasic
epinephrine. reactions are possible after discharge. All
patients with anaphylaxis should be discharged
2. “The patient doesn’t have cutaneous findings, with an epinephrine autoinjector or with a
so it can’t be anaphylaxis.” prescription for an autoinjector, as well as
The diagnosis of anaphylaxis does not require education on how to use it.
cutaneous findings. Acute onset of any 2 of
the systems listed in Table 2 (see page 4) or 8. “My 2-year-old patient had anaphylaxis, but he
hypotension after exposure to a known allergen only weighs 13 kg, so I can’t prescribe him an
is sufficient for the diagnosis of anaphylaxis. epinephrine autoinjector.”
Even in cases of fatal anaphylaxis, patients may Clinical reports published by the American
lack cutaneous signs, so treatment should not be Academy of Pediatrics recommend prescription
delayed due to a lack of cutaneous findings. of the 0.15 mg autoinjector to otherwise healthy
children weighing between 10 kg and 25 kg.102,139
3. “The epinephrine autoinjector is self-explan- Alternatively, a 0.1 mg autoinjector has been
atory. I’m busy. He’ll figure it out if he ever approved for use and can be prescribed, if available.
needs to use it.”
Clinicians frequently neglect to counsel patients 9. “The paramedics are calling for an order to
on appropriate epinephrine autoinjector use. give epinephrine to a 5-year-old girl with a
Many patients do not know how to use their history of bee sting anaphylaxis who now has
autoinjectors properly. Time spent teaching stridor, diffuse wheezing, and an oxygen satu-
a patient how to use the autoinjector may ration of 92% after a bee sting. It sounds like
be lifesaving during a future episode of anaphylaxis, but I’d rather examine the patient
anaphylaxis. myself before giving any medications.”
Delayed epinephrine administration has been
4. “The nurse questioned my IM epinephrine associated with fatal and biphasic anaphylaxis.
order because he’s always given epinephrine Early administration of epinephrine decreases
subcutaneously.” the risk of morbidity and mortality from
The onset of action of epinephrine is more rapid anaphylaxis.54,60-62
with IM administration, and expert guidelines
recommend IM rather than subcutaneous 10. “My patient had an anaphylactic reaction with
administration of epinephrine. syncope, urticaria, and shortness of breath at home.
The mother gave the boy epinephrine, and his
5. “Two patients just arrived with anaphylaxis. symptoms completely resolved before he arrived.
They had both eaten fish at the same restaurant I’m not sure why they even came to the ED.”
tonight. Surely that’s just a coincidence.” There is a risk of biphasic reactions after
Scombroid poisoning presents with similar signs symptom resolution. Guidelines vary in
and symptoms to those of anaphylaxis. It is their recommendations, but all recommend
the likely diagnosis if multiple patients present some period of observation. The patient will
with anaphylaxis-like symptoms after eating the also need a prescription for a replacement
same fish. epinephrine autoinjector.

Copyright © 2019 EB Medicine. All rights reserved. 16 Reprints: www.ebmedicine.net/pempissues


Education on Epinephrine Autoinjector Use for 4 hours. The girl had complete resolution of the facial
Multiple studies of anaphylaxis deaths have dem- swelling and urticarial rash. You reviewed the signs and
onstrated that only a minority of patients who were symptoms of anaphylaxis with the parents, discussed
prescribed an epinephrine autoinjector administered allergen avoidance, and demonstrated appropriate use of
it appropriately during their fatal reaction. Many an epinephrine autoinjector. You discharged the patient
patients did not even have their autoinjector avail- with a prescription for 2 epinephrine autoinjectors and an
able at the time of the fatal reaction.63,64,66 In a clinic- anaphylaxis action plan.
based study, most anaphylaxis patients and their Upon further questioning, the 8-year-old boy told
families were not able to correctly demonstrate the you that he ate a cookie after school. You assumed it
use of an epinephrine autoinjector.100 Additionally, contained an egg product. You administered epinephrine
most resident and attending physicians also could 0.01 mg/kg IM and nebulized albuterol/ipratropium
not demonstrate appropriate use of an epinephrine bromide combination treatments, as well as corticoste-
autoinjector.100 roids and diphenhydramine. The patient’s pulmonary
A survey of 29 attending pediatricians found examination improved dramatically with good aeration,
that only 17% demonstrated to the parents and minimal wheeze, and pulse oximetry of 99% on room air,
patients how to use an epinephrine autoinjector and and his skin returned to normal color. The boy told you
only 24% gave written information at the time of that he felt much better. You observed the patient in the
prescription.100 As multiple epinephrine autoinjec- ED for 6 hours with no recurrence of respiratory distress
tors are available and instructions for use vary by or wheeze, and he had normal vital signs. You instructed
manufacturer, patients must understand how to use the family on the use of an epinephrine autoinjector and
the device they will receive. provided them with an anaphylaxis action plan. The pa-
In general, devices have a safety cap that must tient was discharged with 2 epinephrine autoinjectors and
be removed and then, ensuring that the device is ori- continued treatment for an acute asthma exacerbation.
ented with the needle perpendicular to the patient’s You arranged for follow-up with a specialist in allergy and
outer thigh, the device is pressed firmly into the immunology.
thigh and held for 3 to 10 seconds (depending on the You gave the 15-year-old boy three 20-mL/kg boluses
manufacturer instructions). For children who are un- of normal saline and 3 doses of epinephrine (0.3 mg) IM 5
able to cooperate, the leg should be well restrained to 10 minutes apart for persistent hypotension. His vital
during epinephrine administration. Training autoin- signs improved, with a heart rate of 120 beats/min and
jectors and online videos demonstrating proper use a blood pressure of 90/54 mg Hg. You administered IV
are available from manufacturers. corticosteroids and admitted him to the intensive care unit
for further management.
Summary
Time- and Cost-Effective Strategies
Anaphylaxis can present with a variety of signs and
symptoms and is frequently underdiagnosed. Early • Limit laboratory testing in patients with anaphy-
recognition and treatment of this potentially fatal laxis. Anaphylaxis is a clinical diagnosis, and
condition is vital. IM epinephrine is the cornerstone laboratory testing is rarely helpful. Unless a spe-
of treatment; evidence for other treatment options is cialist in allergy and immunology has requested
lacking. Expert guidelines agree that antihistamines testing during an acute episode, laboratory test-
and corticosteroids are second-line treatments and ing is not necessary.
should never replace or delay epinephrine adminis- • Admission is not necessary in all patients. Most
tration. Patients diagnosed with anaphylaxis should patients do not benefit from prolonged observa-
be discharged with an epinephrine autoinjector tion. Expert guidelines support a 4- to 6-hour ob-
or a prescription for an epinephrine autoinjector servation period. Detailed discharge instructions
and given instructions and/or a demonstration on and discharge with an epinephrine autoinjector
how to use it, education on allergen avoidance, and and demonstration of its use are vital.
instructions to follow up with a specialist in allergy
and immunology. Risk Management Caveat: Consider admission for
patients with severe anaphylaxis, anaphylaxis that is
Case Conclusions slow to respond to epinephrine, a requirement for a
second dose of epinephrine or fluid boluses, or risk
The parents of the 3-year-old girl stated that the girl’s factors such as uncontrolled asthma. Ensure that
previous anaphylactic reaction began with urticaria and patients are able to fill their prescription for the epi-
facial swelling that progressed, resulting in a critical care nephrine autoinjector and are comfortable using it.
admission for airway compromise due to angioedema. Consider admission if the family is unable to access
You administered epinephrine 0.01 mg/kg IM for sus- emergency medical services.
pected anaphylaxis and observed the patient in the ED

June 2019 • www.ebmedicine.net 17 Copyright © 2019 EB Medicine. All rights reserved.


Key Points References
• Anaphylaxis can present with a variety of signs Evidence-based medicine requires a critical ap-
and symptoms. Consider the diagnosis even praisal of the literature based upon study methodol-
in patients who do not present with the classic ogy and number of patients. Not all references are
symptoms of urticaria, angioedema, or wheez- equally robust. The findings of a large, prospective,
ing. Two studies found that approximately half randomized, and blinded trial should carry more
of patients meeting criteria for food-related ana- weight than a case report.
phylaxis did not receive a discharge diagnosis of To help the reader judge the strength of each
anaphylaxis.2,3 reference, pertinent information about the study is
• IM epinephrine is recommended as the first-line included in bold type following the reference, where
treatment in all anaphylaxis treatment guide- available. In addition, the most informative referenc-
lines. Multiple studies have found that patients es cited in this paper, as determined by the authors,
diagnosed with anaphylaxis frequently do not are noted by an asterisk (*) next to the number of the
receive IM epinephrine by EMS providers or in reference.
the ED. Patients also underuse their epinephrine
autoinjectors.100 1.* Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second
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52. Lee S, Bellolio MF, Hess EP, et al. Predictors of biphasic tients, 658 anaphylaxis cases)
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81. Bains SN, Hsieh FH. Current approaches to the diagnosis
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82. Brockow K, Jofer C, Behrendt H, et al. Anaphylaxis in pa-
62. Bock SA, Munoz-Furlong A, Sampson HA. Further fatali- tients with mastocytosis: a study on history, clinical features
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83. Capps JA, Sharma V, Arkwright PD. Prevalence, outcome
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1150. (Case series; 48 patients) Resuscitation. 2010;81(6):653-657. (Retrospective; 816 allergic
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to food in the United Kingdom, 1999-2006. J Allergy Clin Im- 84. Kane KE, Cone DC. Anaphylaxis in the prehospital setting. J
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65. Greenhawt MJ, Singer AM, Baptist AP. Food allergy and 85. Manivannan V, Hyde RJ, Hankins DG, et al. Epinephrine use
food allergy attitudes among college students. J Allergy Clin and outcomes in anaphylaxis patients transported by emer-
Immunol. 2009;124(2):323-327. (Survey; 513 respondents) gency medical services. Am J Emerg Med. 2014;32(9):1097-
66. Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: 1102. (Cohort study; 103 patients)
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Allergy Asthma Immunol. 2007;98(3):252-257. (Retrospective; emergency medical services in privately insured patients:
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67. Sicherer SH, Sampson HA. Food allergy: epidemiology, (Retrospective study; 239,243 children)
pathogenesis, diagnosis, and treatment. J Allergy Clin Immu- 87. Rea TD, Edwards C, Murray JA, et al. Epinephrine use by

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emergency medical technicians for presumed anaphylaxis. Allergy Clin Immunol. 2001;108(5):871-873. (Prospective ran-
Prehosp Emerg Care. 2004;8(4):405-410. (Case control; 44 domized; 13 patients)
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88. Fortenberry JE, Laine J, Shalit M. Use of epinephrine for ana- nephrine dosing leading to iatrogenic overdose: a life-threat-
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89. Tiyyagura GK, Arnold L, Cone DC, et al. Pediatric anaphy- good thing, is it bad? Adrenaline on trial. N Z Med J.
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90. Cristiano LM, Hiestand B, Caldwell JW, et al. Prehospital dial ischemia. Pediatr Emerg Care. 1999;15(2):116-118. (Case
administration of epinephrine in pediatric anaphylaxis - a report)
statewide perspective. Prehosp Emerg Care. 2018;22(4):452- 108. Litvinov IV, Kotowycz MA, Wassmann S. Iatrogenic
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91. Jacobsen RC, Toy S, Bonham AJ, et al. Anaphylaxis knowl- direct evidence supporting the role of catecholamines in the
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(Review) 110. Wheeler DW, Carter JJ, Murray LJ, et al. The effect of drug
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Immunol. 2004;113(2):347-352. (Retrospective; 678 patients) 112. Reed MJ, Fothergill J. The Livingston Paediatric Dose Calcu-
96. Clark S, Long AA, Gaeta TJ, et al. Multicenter study of lator. Emerg Med J. 2007;24(8):567-568. (Report)
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97. Smit DV, Cameron PA, Rainer TH. Anaphylaxis presenta- 2007;62(8):857-871. (Position paper)
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2005;28(4):381-388. (Retrospective; 282 patients) 115. Nurmatov UB, Rhatigan E, Simons FE, et al. H2-antihista-
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99. Russell S, Monroe K, Losek JD. Anaphylaxis management mines reduce progression to anaphylaxis among emergency
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100. Sicherer SH, Forman JA, Noone SA. Use assessment of self- antagonists in the treatment of acute allergic reactions. Ann
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characteristics, triggers, and management. J Allergy Clin Im- 2000;36(5):462-468. (Prospective randomized; 91 patients)
munol. 2013;132(3):739-741. (Prospective and retrospective; 119. Lieberman P. The use of antihistamines in the prevention
168 anaphylaxis cases) and treatment of anaphylaxis and anaphylactoid reactions. J
102.* Sicherer SH, Simons FER, Section on Allergy and Immunol- Allergy Clin Immunol. 1990;86(4 Pt 2):684-686. (Review)
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laxis. Pediatrics. 2017;139(3). (Clinical report) lactoid reactions to iodinated radiological contrast media: a
103. Simons FE, Roberts JR, Gu X, et al. Epinephrine absorption systematic review. BMC Med Imaging. 2006;6:2. (Systematic
in children with a history of anaphylaxis. J Allergy Clin Im- review)
munol. 1998;101(1 Pt 1):33-37. (Prospective randomized; 17 121. Lieberman P, Kemp SF, Oppenheimer J, et al. The diagno-
patients) sis and management of anaphylaxis: an updated practice
104. Simons FE, Gu X, Simons KJ. Epinephrine absorption in parameter. J Allergy Clin Immunol. 2005;115(3):S483-S523.
adults: intramuscular versus subcutaneous injection. J (Practice parameter)

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122.* Michelson KA, Monuteaux MC, Neuman MI. Glucocorti- approved drug products with therapeutic equivalence
coids and hospital length of stay for children with anaphy- evaluations. Available at: https://www.accessdata.fda.gov/
laxis: a retrospective study. J Pediatr. 2015;167(3):719-724. scripts/cder/ob/index.cfm. Accessed May 15, 2019. (Online
(Retrospective; 5203 patients) FDA pharmaceutical database)
123. Lang DM. Do beta-blockers really enhance the risk of ana- 141. Simons FE, Chan ES, Gu X, et al. Epinephrine for the out-
phylaxis during immunotherapy? Curr Allergy Asthma Rep. of-hospital (first-aid) treatment of anaphylaxis in infants: is
2008;8(1):37-44. (Review) the ampule/syringe/needle method practical? J Allergy Clin
124. Lang DM, Alpern MB, Visintainer PF, et al. Increased risk Immunol. 2001;108(6):1040-1044. (Prospective control study;
for anaphylactoid reaction from contrast media in patients 18 parents, 54 healthcare workers)
on beta-adrenergic blockers or with asthma. Ann Intern Med. 142. Brown JC, Tuuri RE, Akhter S, et al. Lacerations and embed-
1991;115(4):270-276. (Retrospective case-control; 28,978 ded needles caused by epinephrine autoinjector use in
contrast exposures, 49 patients with moderate to severe children. Ann Emerg Med. 2016;67(3):307-315. (Case series; 22
reactions) cases)
125. Lang DM, Alpern MB, Visintainer PF, et al. Elevated risk of 143. Muck AE, Bebarta VS, Borys DJ, et al. Six years of epineph-
anaphylactoid reaction from radiographic contrast media rine digital injections: absence of significant local or systemic
is associated with both beta-blocker exposure and cardio- effects. Ann Emerg Med. 2010;56(3):270-274. (Retrospective
vascular disorders. Arch Intern Med. 1993;153(17):2033-2040. cohort study; 365 cases)
(Retrospective case-control; 34,371 contrast exposure, 122
anaphylactoid reactions)
126. White JL, Greger KC, Lee S, et al. Patients taking beta- CME Questions
blockers do not require increased doses of epinephrine for
anaphylaxis. J Allergy Clin Immunol Pract. 2018;6(5):1553-
1558. (Retrospective study; 789 patients)
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128. Javeed N, Javeed H, Javeed S, et al. Refractory anaphylactoid includes 4 AMA PRA Category 1 CreditsTM, 4 ACEP
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130. Castells MC, Horan RF, Sheffer AL. Exercise-induced ana-
phylaxis. Curr Allergy Asthma Rep. 2003;3(1):15-21. (Report) www.ebmedicine.net/P0619.
131. Du Toit G. Food-dependent exercise-induced anaphylaxis
in childhood. Pediatr Allergy Immunol. 2007;18(5):455-463.
(Review)
132. Hussain AM, Yousuf B, Khan MA, et al. Vasopressin for the
management of catecholamine-resistant anaphylactic shock.
Singapore Med J. 2008;49(9):e225-e228. (Case report)
133. Schummer C, Wirsing M, Schummer W. The pivotal role of
vasopressin in refractory anaphylactic shock. Anesth Analg.
2008;107(2):620-624. (Case series; 6 patients)
134. Osman BM, Maga JM, Baquero SM. Case report: manage- 1. Which of the following is TRUE regarding the
ment of differential diagnosis and treatment of severe diagnosis and treatment of anaphylaxis?
anaphylaxis in the setting of spinal anesthesia. J Clin Anesth. a. Studies have demonstrated that anaphylaxis
2016;35:145-149. (Case report) is overdiagnosed and overtreated by EMS
135. Ma DS, Kim T-H, Keum MA, et al. Management of cardiac personnel and emergency clinicians.
arrest following anaphylactic reaction to cisatracurium using
b. Studies have demonstrated that anaphylaxis
extracorporeal membrane oxygenation. Korean J Crit Care
Med. 2015;30(1):42-45. (Case report) is underrecognized in EDs but, when
136. Douglas DM, Sukenick E, Andrade WP, et al. Biphasic diagnosed, is almost always treated
systemic anaphylaxis: an inpatient and outpatient study. J appropriately.
Allergy Clin Immunol. 1994;93(6):977-985. (Retrospective; 94 c. Studies have demonstrated that EMS
patients) personnel overdiagnose and overtreat
137. Simons FE, Gu X, Silver NA, et al. EpiPen Jr versus EpiPen anaphylaxis, but emergency clinicians
in young children weighing 15 to 30 kg at risk for anaphylax- appropriately diagnose and treat
is. J Allergy Clin Immunol. 2002;109(1):171-175. (Prospective
randomized; 10 patients)
anaphylaxis.
138. Sampson HA. Anaphylaxis and emergency treatment. Pediat-
d. Studies have demonstrated that EMS
rics. 2003;111(6 Pt 3):1601-1608. (Review) personnel and emergency clinicians
139. Sicherer SH, Simons FE, the Section on Allergy and Immu- undertreat anaphylaxis.
nology, et al. Self-injectable epinephrine for first-aid manage-
ment of anaphylaxis. Pediatrics. 2007;119(3):638-646. (Expert
guideline)
140. United States Food and Drug Administration. Orange Book:

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2. Which of the following patients meets the 7. Which of the following medications is the
criteria for anaphylaxis? most important to administer immediately to a
a. A 10-year-old boy with a known peanut patient with an anaphylactic reaction?
allergy who has a blood pressure of 82/30 a. Diphenhydramine
mm Hg after accidentally eating a dessert b. Ranitidine
containing peanuts at a party c. Methylprednisolone
b. A 14-year-old girl without known allergies d. Epinephrine
with isolated syncope after a bee sting
who is now asymptomatic with a normal 8. What route and dose of epinephrine is the
physical examination most appropriate initial treatment in a 30-kg
c. A 9-month-old boy with diffuse urticaria child with diffuse urticaria, stridor, and lip
and pruritus but otherwise normal vital swelling?
signs and physical examination after eating a. 0.5 mL nebulized racemic epinephrine
an egg for the first time b. 0.3 mL 1 mg/1 mL epinephrine
d. A 3-year-old girl with a history of atopic administered subcutaneously in the upper
dermatitis who presents with 2 days of arm
profuse rhinorrhea and cough and 2 hours c. 0.3 mL 1 mg/1 mL epinephrine
of noisy breathing and diffuse wheeze on administered intramuscularly in the thigh
pulmonary examination d. 3 mL 0.1 mg/1 mL epinephrine
administered intravenously
3. Which of the following diagnostic criteria for
anaphylaxis is CORRECT? 9. Which of the following is TRUE regarding IV
a. Cutaneous symptoms are required for the epinephrine for anaphylaxis?
diagnosis of anaphylaxis. a. If an IV line has been established,
b. Signs and symptoms in 2 organ systems are IV epinephrine is preferred over IM
required for the diagnosis of anaphylaxis. epinephrine for first-line therapy.
c. Isolated hypotension after exposure to a b. The 1 mg/1 mL concentration is
known allergen for the patient is consistent recommended for IV administration in
with anaphylaxis. anaphylaxis.
d. Histamine and tryptase levels are necessary c. Cardiac arrest is the only appropriate
to rule out other etiologies. indication for IV epinephrine.
d. IV epinephrine is indicated if multiple bolus
4. Which of the following is TRUE regarding doses of IM epinephrine fail to reverse
biphasic reactions? hypotension or other severe signs.
a. Early administration of antihistamines
decreases the risk of a biphasic reaction. 10. Which of the following is TRUE regarding
b. The need for a second dose of epinephrine is fatal anaphylaxis?
a potential risk factor for a biphasic reaction. a. Approximately 3% of anaphylaxis episodes
c. Biphasic reactions occur in 30% of pediatric are fatal.
patients with anaphylaxis. b. Most deaths from anaphylaxis occur within
d. Biphasic reactions most commonly occur > 6 4 hours of allergen exposure.
hours after the initial reaction. c. Antihistamine treatment has been
demonstrated to reduce the risk of death in
5. Which of the following is a risk factor for fatal food-related anaphylaxis.
anaphylaxis? d. Delayed anaphylaxis deaths are most
a. Presence of cutaneous symptoms commonly due to insect stings.
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

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son, MD, MPH, Emergency Sciences;
Joelle N. Simpssor of Pediatrics and of Medicine & Health
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Garth Meckl
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Chief, Pediat
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David M. Walkeric Emergency
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Professor Sanzari Childre sity
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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
ic Emergency Specialist, Associate Medicine,
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,
Honolu Assistant ProfessMedicine, Harvard Chief, Pediat Southwestern
Associate ,

Candidate Fellows of the American Academy of Pediatrics.


ement FACEP
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,
ce, CA FAAP ency Medic Chief and Fellow ne, Boston Emergency , TX
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
Medic
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sor of University
cksonville,
Depar
Children's
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
ency

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

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

up care for patients with anaphylaxis.


Jeffrey R. Avner, MD, FAAP of and Pediatrics, Chief and Medical of Emergency Medicine, Boston
Medicine at UCLA; EMS Fellowship Children’s Hospital, Boston, Professor of Pediatrics and
Chairman, Department of Director, Harbor-UCLA Medical Director, Pediatric Emergency MA Emergency Medicine; Division
Pediatrics, Professor of Clinical Center, Department of Emergency Medicine Division, University James Naprawa, MD Chief, Pediatric Emergency
Pediatrics, Maimonides Children's Medicine, Los Angeles, CA of Florida College of Medicine- Attending Physician, Emergency Medicine, UT Southwestern
Hospital of Brooklyn, Brooklyn, Jacksonville, Jacksonville, Department USCF Benioff Medical Center; Director
NY Michael J. Gerardi, MD, FAAP, FL 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 Medicine
Professor of Emergency Medicine at Hofstra/Northwell, New Hospital Imperial College Trust,
Chief Quality and Patient Safety Tommy Y. Kim, MD, FAAP, Hyde
and Pediatrics; Section Chief, FACEP Park, NY London, UK; Nonclinical Instructor
Officer, Professor of Pediatrics Associate Professor of Pediatric of Emergency Medicine, Icahn
Pediatric Emergency Medicine; and Steven Rogers, MD
Emergency Medicine, Attending Emergency Medicine, University School of Medicine at Mount
Medical Director, Upstate Poison of

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

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