120 Anaphylaxis

• E nvironmental exposures: Bee or wasp sting, • R apidly establish intravenous (IV) access and
BASIC INFORMATION snake venom, fire ant venom administer IV fluids (i.e., normal saline).
• Blood products: Plasma, immunoglobulin, • Cardiac monitoring is recommended.
DEFINITION cryoprecipitate, whole blood
• Latex ACUTE GENERAL Rx
Anaphylaxis is a severe allergic reaction that is
rapid in onset and life-threatening. In anaphy- • Exercise • 0.3 to 0.5 mg intramuscular epinephrine
laxis, immunoglobulin E (IgE)-mediated systemic • Box 1 summarizes agents frequently associ- (1:1000 concentration) should be rapidly
degranulation of mast cells causes respiratory, ated with immune and nonimmune types of administered for adults and children >30
cardiovascular, gastrointestinal, and mucocuta- anaphylaxis kg in the lateral thigh. 0.01 mg/kg intra-
neous signs or symptoms. Anaphylactoid reaction muscular epinephrine (1:1000 concentration)
should be administered for children <30
is an entity closely related to anaphylaxis and DIAGNOSIS kg. Intramuscular administration is preferred
is caused by release of mast cells and baso-
phil mediators triggered by non–IgE-mediated because it provides more reliable and quicker
DIFFERENTIAL DIAGNOSIS rise to effective plasma levels. The dose may
events.
• Allergic reaction be repeated after approximately 5 to 15
SYNONYM • Other causes of shock such as sepsis or min if symptoms persist. Patients with mild
pulmonary embolism episodes should be observed for 1 hour after
Anaphylactoid reaction
• Endocrine disorders (carcinoid, adrenal crisis, resolution of symptoms. Patients with severe
ICD-10CM CODES paradoxical pheochromocytoma) symptoms should be observed for at least 6
T78.2 Anaphylactic shock, unspecified, • Systemic mastocytosis hours.
initial encounter • Serum sickness • Adjunct therapies include H1 and H2 receptor
T78.00XA Anaphylactic reaction due to • Severe asthma (the key clinical difference is antagonists such as diphenhydramine 25 to
unspecified food, initial encounter the abrupt onset of symptoms in anaphylaxis 50 mg IV or intramuscular (or by mouth [PO]
T80.52XA Anaphylactic reaction due to versus a history of progressive worsening of in mild cases) and famotidine 20 to 40 mg
vaccination, initial encounter symptoms) IV (or PO in mild cases). Although useful to
T63.94XA Toxic effect of contact with • Scombroid poisoning improve cutaneous erythema and pruritus,
unspecified venomous animal, • Localized angioedema H1 antagonists are not as effective as epi-
undetermined, initial encounter • Acute urticaria nephrine, since onset of action is 1 to 2 hr,
• Presyncopal syndromes including vasovagal and they are not effective in reversing upper
EPIDEMIOLOGY & reactions airway obstruction or improving hypotension.
DEMOGRAPHICS • Airway foreign body • Corticosteroids are not useful in the acute
• Globus hystericus, anxiety disorder episode because of their slow onset of
INCIDENCE: The incidence of anaphylaxis in
the U.S. is 50 to 2000 episodes per 100,000 action; however, they should be administered
WORKUP in most cases to prevent prolonged or recur-
persons. Lifetime prevalence is 0.05% to 2%, Workup is aimed at ruling out other conditions
with a mortality rate of 1%. Anaphylaxis rates rent anaphylaxis. Commonly used agents are
that may mimic anaphylaxis. Given the poten- prednisone, methylprednisolone 40 to 250
are 0.0004% for food, 0.7% to 10% for penicil- tially life-threatening nature of anaphylaxis,
lin, 0.22% to 1% for contrast media, and 0.5% mg IV in adults (1 to 2 mg/kg in children), or
treatment should not be delayed. Clinical criteria dexamethasone.
to 5% after insect stings. Mortality rates are for diagnosing anaphylaxis are summarized in
0.65% to 2% of patients presenting with ana- • Aerosolized β-agonists (e.g., albuterol, 2.5
Box 2. to 5.0 mg, repeat prn 20 min) are useful to
phylaxis. Annual mortality is nearly 500 to 1000
persons/yr in the U.S. control bronchospasm.
LABORATORY TESTS • Vasopressor therapy with IV epinephrine
PHYSICAL FINDINGS & CLINICAL • Laboratory evaluation is generally not helpful (1:10,000 concentration) indicated in patients
PRESENTATION because anaphylaxis is typically a clinical with refractory hypotension/cardiovascular
diagnosis. collapse after crystalloid resuscitation.
• Mucocutaneous: Urticaria, pruritus, skin • Elevated serum and urine histamine levels
flushing, angioedema (Table E1) • Patients taking beta-blocking medications
and serum tryptase levels can be useful for may be refractory to initial treatment; con-
• Respiratory: Dyspnea, cough, wheezing, diagnosis of anaphylaxis, but these tests are
hypoxia, stridor, rhinitis sider administration of IV glucagon.
not commonly available in the emergency • Table 3 summarizes drugs and other agents
• Gastrointestinal: Nausea, vomiting, diarrhea, setting.
dysphagia, abdominal pain used in anaphylaxis therapy.
• Cardiovascular: Hypotension, tachycardia, • Fig. E1 illustrates an algorithm for the man-
IMAGING STUDIES agement of a patient with severe anaphylaxis.
weakness, dizziness, syncope, malaise, vas- • Generally not helpful.
cular collapse (Table E2) • Chest radiography for evaluation of foreign
body aspiration or pulmonary pathology is PEARLS &
ETIOLOGY
• Anaphylaxis results from a sudden system-
indicated in patients with acute respiratory CONSIDERATIONS
compromise.
atic release of histamine and other inflam- • Consider ECG in all patients with sudden COMMENTS
matory mediators from basophils and mast loss of consciousness or reports of chest • Patient education regarding the nature of the
cells. Virtually any substance may induce pain or dyspnea and in any elderly patient. illness and preventive measures is recom-
anaphylaxis. In an acute setting, the cause of ECG in anaphylaxis usually reveals sinus mended. A documented history of previous
anaphylaxis is often unidentifiable: tachycardia. anaphylactic episodes or known triggers is
• Foods and food additives: Peanuts, tree the most reliable method of identifying indi-
nuts, eggs, shellfish, fish, cow’s milk, fruits, viduals at risk.
soy TREATMENT • Prescription for a prefilled epinephrine
• Medications: Antibiotics (especially penicil- syringe (EpiPen or EpiPen Jr.) should be
lins and sulfa-based agents), insulin, allergen NONPHARMACOLOGIC THERAPY given, and the patient should be instructed on
extracts, opiates, vaccines, NSAIDs, contrast • Establish and protect airway. Provide supple- the use of this emergency kit, and to carry it
media, streptokinase mental O2 if indicated. with them at all times. School-aged children

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Anaphylaxis 120.e1

TABLE E1 Dynamics of Cardiovascular Abnormalities in Anaphylactic Shock

At Onset of Reaction Early Stage (Minutes) with No Treatment Prolonged Shock
Blood pressure ↓ ↓↓ ↓↓↓
Pulse ↑ ↑ ↑↑
Cardiac output ↑ ↓ ↓↓
PVR ↓ →↓* →↑↓*
Intravascular volume →↓ ↓ ↓↓↓

*Peripheral vascular resistance (PVR) can vary, likely depending on internal compensation response.
From LoVerde D, Iweala OI, Eginli A, Krishnaswamy G. Anaphylaxis. Chest. 2018;153(2):528-543. https://doi.org/10.1016/j.chest.2017.07.033

TABLE E2 Signs and Symptoms of Anaphylaxis: Frequency

of Occurrence
Sign or Symptom Percentage of Cases (%)
Cutaneous >90
Urticaria and angioedema 85-90
Flush 45-55
Pruritus without rash 2-5
Respiratory 40-60
Dyspnea, wheeze 45-50
Upper airway angioedema 50-60
Rhinitis 15-20
Dizziness, syncope, hypotension 30-35
Abdominal
Nausea, vomiting, diarrhea, cramping 25-30
pain
Miscellaneous
Headache 5-8
Substernal pain 4-6
Seizure 1-2

Anaphylaxis

1st line

Epinephrine 0.3−0.5 mg repeated as needed

Fluid boluses if hemoconcentration or hypotensive
Avoidance/elimination of causal agent
O2 for SpO2 93%−95%
Airway protection (difficult airway procedures)
Methylprednisolone 1 mg/kg/day for 72 hr max
(+ antihistaminics)

2nd line
(persisting shock)

Methylene blue
Vasopressin
Angiotensin ?
Glucagon

FIG. E1 Management of a patient with severe anaphylaxis. O2, Oxygen; SpO2, oxygen saturation mea-
sured by pulse oximetry. (From Parrillo JE, Dellinger RP: Critical care medicine, principles of diagnosis and
management in the adult, ed 5, Philadelphia, 2019, Elsevier.)

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 Anaphylaxis 121

BOX 1  Agents Frequently Associated With Immune and Nonimmune Types of Anaphylaxis
A
Immunologic Mechanisms
Immunoglobulin E (IgE)-mediated:
Food (nuts, shellfish, fruits, etc.)
Venoms (stinging insects)
Medications (β-lactam antibiotics, NSAIDs, neuromuscular blocking agents, etc.)
Natural rubber latex
Seminal fluid
Radiocontrast media (in some cases)
IgE-Independent
Radiocontrast media (in most cases)
Dextrans

and Disorders
Diseases
Monoclonal antibodies (Rituximab)
Medications (β-lactam antibiotics, NSAIDs, etc.)
Natural rubber latex
Seminal fluid
Nonimmunologic Mechanisms
Medications (opioids, protamine, etc.)
From Parrillo JE, Dellinger RP. Critical care medicine, principles of diagnosis and management in the adult, ed 5, Philadelphia, 2019, Elsevier.
I
BOX 2  Clinical Criteria for Diagnosing Anaphylaxis
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized urticaria,
itching or flushing, swollen lips/tongue/uvula) and at least one of the following:
a. Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia collapse, syncope, incontinence)
OR
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (e.g., generalized urticaria, itch/flush, swollen lips/tongue/uvula)
b. Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced blood pressure or associated symptoms (e.g., hypotonia collapse, syncope, incontinence)
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
OR
3. Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours)
a. Infants and children: Low systolic blood pressure (age-specific) or >30% decrease in systolic blood pressure
b. Adults: Systolic blood pressure of <90 mm Hg or >30% decrease from that person’s baseline
From Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium, J Allergy Clin Immunol 117(2):391-397, 2006. https://doi.org/10.1016/j.jaci.2005.12.1303.

TABLE 3 Management of a Patient With Anaphylaxis

Treatment Mechanism(s) of Effect Dosage(s) Comments; Adverse Reactions
PATIENT EMERGENCY MANAGEMENT (DEPENDENT ON SEVERITY OF SYMPTOMS)
Epinephrine (adrenaline) α1-, β1-, β2-Adrenergic effects 0.01 mg/kg, up to 0.5 mg IM in lateral thigh Tachycardia, hypertension, nervousness,
Adrenaclick, Auvi-Q, EpiPen Jr./EpiPen: headache, nausea, irritability, tremor
0.15 mg IM for 8-25 kg
0.3 mg IM for 25 kg or more
Epinephrine autoinjector:
0.1 mg for 7.5-15 kg
0.15 mg for 15-25 kg
0.3 mg for 25 kg or more
Cetirizine (liquid) Antihistamine (competitive of Cetirizine liquid: 5 mg/5 ml0.25 mg/kg, up to 10 mg Hypotension, tachycardia, somnolence
H1 receptor) PO
Alternative: Diphenhydramine Antihistamine (competitive of 1.25 mg/kg up to 50 mg PO or IM Hypotension, tachycardia, somnolence,
H1 receptor) paradoxical excitement
Transport to an emergency facility
EMERGENCY PERSONNEL MANAGEMENT (DEPENDENT ON SEVERITY OF SYMPTOMS)
Epinephrine (adrenaline) α1-, β1-, β2-Adrenergic effects 0.01 mg/kg, up to 0.5 mg IM in lateral thigh Tachycardia, hypertension, nervousness,
Epinephrine autoinjector: headache, nausea, irritability, tremor
0.1 mg for 7.5-15 kg
0.15 mg for 15-25 kg
0.3 mg for 25 kg or more
0.01 ml/kg/dose of 1:1,000 (vial) solution, up to 0.5
ml IM
May repeat every 10-15 min
For severe hypotension: 0.01 ml/kg/dose of 1:10,000
slow IV push
Continued
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122 Anaphylaxis

TABLE 3 Management of a Patient With Anaphylaxis—cont’d

Treatment Mechanism(s) of Effect Dosage(s) Comments; Adverse Reactions
SUPPLEMENTAL OXYGEN AND AIRWAY MANAGEMENT
Volume Expanders
Crystalloids (normal saline or 30 ml/kg in 1st hr Rate titrated against BP response
Ringer lactate) If tolerated, place patient supine with
legs raised
Colloids (hydroxyethyl starch) 10 ml/kg rapidly followed by slow infusion Rate titrated against BP response
If tolerated, place patient supine with
legs raised
Antihistamines
Cetirizine (liquid) Antihistamine (competitive of Cetirizine liquid: 5 mg/5 ml Hypotension, tachycardia, somnolence
H1 receptor) 0.25 mg/kg, up to 10 mg PO
Alternative: Diphenhydramine Antihistamine (competitive of 1.25 mg/kg, up to 50 mg PO, IM, or IV Hypotension, tachycardia, somnolence,
H1 receptor) paradoxic excitement
Ranitidine Antihistamine (competitive of 1 mg/kg, up to 50 mg IV Headache, mental confusion
H2 receptor) Should be administered slowly
Alternative: Cimetidine Antihistamine (competitive of 4 mg/kg, up to 200 mg IV Headache, mental confusion
H2 receptor) Should be administered slowly
Corticosteroids
Methylprednisolone Antiinflammatory Solu-Medrol (IV): 1-2 mg/kg, up to 125 mg IV Hypertension, edema, nervousness,
Depo-Medrol (IM): 1 mg/kg, up to 80 mg IM agitation
Prednisone Antiinflammatory 1 mg/kg up, to 75 mg PO Hypertension, edema, nervousness,
agitation
Nebulized albuterol β-Agonist 0.83 mg/ml (3 ml) via mask with O2 Palpitations, nervousness, CNS
stimulation, tachycardia; use to
supplement epinephrine when
bronchospasm appears unresponsive;
may repeat
POSTEMERGENCY MANAGEMENT
Antihistamine Cetirizine (5-10 mg qd) or
loratadine (5-10 mg qd) for
3 days
Corticosteroids Optional: Oral prednisone (1
mg/kg up to 75 mg) daily
for 3 days
Preventive Treatment
Prescription for epinephrine autoinjector and antihistamine
Provide written plan outlining patient emergency management (may download form from http://www.aap.org or http://www.foodallergy.org)
Follow-up evaluation to determine/confirm etiology
Immunotherapy for insect sting allergy
Patient Education
Instruction on avoidance of causative agent
Information on recognizing early signs of anaphylaxis
Stress early treatment of allergic symptoms to avoid systemic anaphylaxis
Encourage wearing medical identification jewelry

BP, Blood pressure; CNS, central nervous system; IM, intramuscularly; IV, intravenously; PO, orally; qd, every day.
From Kliegman RM, Geme JS. Nelson Textbook of Pediatrics, Philadelphia, 2019, Elsevier.

should keep an additional EpiPen at school reaction. However, pretreatment regimens SUGGESTED READINGS
with the appropriate staff. with methylprednisolone or diphenhydr- Available on the eBook. See ad in front of
• Patients should also be advised to carry or amine, exist for those who have had contrast book for details.
wear a MedicAlert ID describing substances reactions in the past.
that have caused anaphylaxis. • Venom immunotherapy immediately after a AUTHORS: Rory Merritt, MD, MEHP, and
• Avoidance of radiologic contrast is also rec- sting is effective and recommended for up to Rachel Smith Shain, MD
ommended in those who have had a prior 5 yr after the anaphylactic incident.

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Anaphylaxis 122.e1

SUGGESTED READINGS
Lieberman PL: Recognition and first-line treatment of anaphylaxis, Am J Med
127(1 Suppl):S6-S11, 2014. https://doi.org/10.1016/j.amjmed.2013.09.008.
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Allergy Asthma Immunol 115(5):341-384, 2015. https://doi.org/10.1016/j.
anai.2015.07.019.
LoVerde D et al: Anaphylaxis, Chest 153(2):528-543, 2018. https://doi.
org/10.1016/j.chest.2017.07.033.
Mustafa SS: Anaphylaxis. Medscape website. Published May 16, 2018. Available at
http://emedicine.medscape.com/article/135065-overview#a0101. Accessed
August, 21 2021.
Nowak RM, Macias CG: Anaphylaxis on the other front line: perspectives from the
emergency department, Am J Med 127(1 Suppl):S34-S44, 2014. https://doi.
org/10.1016/j.amjmed.2013.09.012.
Pflipsen MC, Vega Colon KM: Anaphylaxis: recognition and management, Am Fam
Physician 102(6):355-362, 2020.
Sampson HA et al: Second symposium on the definition and management of ana-
phylaxis: summary report--Second National Institute of Allergy and Infectious
Disease/Food Allergy and Anaphylaxis Network symposium, J Allergy Clin
Immunol 117(2):391-397, 2006. https://doi.org/10.1016/j.jaci.2005.12.1303.
Sclar DA, Lieberman PL: Anaphylaxis: underdiagnosed, underreported, and
undertreated, Am J Med 127(1 Suppl):S1-S5, 2014. https://doi.org/10.1016/j.
amjmed.2013.09.007.

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