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I. Definition

TABLE 1 Clinical Criteria for Diagnosing Anaphylaxis (Fulfilling Any 1 Criterion Indicates That Anaphylaxis Is Highly Likely)7

Criterion 1Acute onset of an illness (minutes to several hours) with involvement of the skin and/or mucosal tissue (eg, generalized hives, pruritus, or flushing, swollen lips/tongue/uvula) and at least 1 of the following:
  1. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
  2. Reduced blood pressure or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)
Criterion 2Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):
  1. Involvement of the skin/mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula)
  2. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
  3. Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
  4. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)
Criterion 3Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours)

Less common presentations also occur (eg, sudden isolated hypotension without a known allergen exposure). Additional symptoms and signs that may occur during anaphylaxis include morbilliform rash, conjunctival erythema, pruritus and tightness in the throat, dysphagia, dysphonia, hoarseness, dry staccato cough, sensation of pruritus in the external auditory canals, nasal pruritus, nasal congestion, rhinorrhea, sneezing, chest pain, dysrhythmia, feeling of faintness/dizziness (near-syncope), paleness, cyanosis, confusion/altered mental status, an aura of doom, and uterine contractions. Skin signs aid in recognition but may be absent or not observed in 10% of children with anaphylaxis; moreover, they may not be observed in reactions that end in fatality.

The clinical criteria were adapted from Sampson HA, Muñoz-Furlong A, Campbell RL, et al. J Allergy Clin Immunol. 2006;117:391-397.

II. Emergency department treatment

  • Epinephrine (1:1000) is the medication of choice for first-aid treatment of an episode of anaphylaxis. Prompt injection of epinephrine is nearly always effective in the treatment of anaphylaxis, and delayed injection of epinephrine is associated with poor outcomes including fatality. Antihistamines and, for those with asthma, inhaled selective ß2-adrenergic agonists such as albuterol provide adjunctive therapy but cannot replace epinephrine.

    The recommended epinephrine dose for anaphylaxis in children is 0.01 mg/kg, up to 0.3 mg or 0.01 ml/kg, up to 0.3 ml of epinephrine (1:1000).

    Intramuscular injection of epinephrine (1:1000) into the lateral thigh (vastus lateralis) is the preferred route for therapy, assuming that an early peak epinephrine concentration is important to effective management. Intravenous administration of epinephrine carries increased risks of dilution errors and dosing errors, with consequent increased risk of overdose and adverse effects such as cardiac dysrhythmias.
  • Normal saline rapid infusion (20 ml/kg) for hypotension. Trendelenburg position. Repeat NS bolus times 2 (total of 3 boluses or total 60 ml/kg) for hypotension refractory to intramuscular epinephrine and preceding normal saline infusion.
  • Epinephrine continuous IV infusion, 0.1 to 0.5 mcg/kg/min for hypotension refractory to above.
  • Methylprednisolone (solu-medrol) IV, 2 mg/kg
  • H1 - receptor antihistamine (diphenhydramine) IV, IM or PO, 1 to 2 mg/kg, max dose 50 mg.
  • H2 - receptor antihistamine (cimetidine) IV, 5 mg/kg, max 300 mg.

III. Indications for Hospitalization

  • Unresolved symptoms and signs of anaphylaxis.
  • High risk for biphasic reaction (delayed epinephrine treatment, greater than 3 hours from onset of symptoms and signs).
  • Co-morbidities of concern

IV. Outpatient management

  • Epinephrine Autoinjector for patients with anaphylaxis or patients who are at risk for developing anaphylaxis. See table 2 for dose recommendations. See Table 3 for at risk patients.
  • Patients and caregivers must be carefully instructed on the technique for use of, and indications for, self-injectable epinephrine, how to recognize the symptoms of anaphylaxis, and the need to activate emergency services (call 911 or equivalent) in the event of anaphylaxis. Instructions on allergen avoidance are key.
  • Optimally, evaluation by an allergy/immunology specialist with American Board of Allergy and Immunology or international equivalent certification should be obtained to confirm allergic triggers, to provide education on trigger avoidance, and to initiate specific preventive treatment (eg, venom-injection immunotherapy for insect-sting anaphylaxis).
  • Written emergency action plans and review of care plans in the child's medical home with specific responsibilities for school, child care, or camp personnel; families; and children are needed to ensure a safe environment for those at risk. Examples of written plans that can be personalized are available at the following Web site www.foodallergy.org.
  • Another resource for parents to help with keeping their child safe and their medications secure especially for vacations and camp experiences is SAFETY SACK at http://www.safetysack.com/action_plans.cfm.
  • A sample ACTION PLAN is provided on the last 2 pages of these guidelines.

TABLE 2 Epinephrine Autoinjectors for Infants and Children: Dilemmas in Dosing and Possible Solutions19

Patient's Weight, kg (lb)Optimal Dose (0.01 mg/kg), mgAvailability of AutoinjectoraAlternatives/ImplicationsbComments/Recommendationsc
<= 10 (<= 22)<=0.10NoFixed-dose 0.15-mg autoinjector provides >=1.5-fold overdose; ampule/syringe/needle technique may lead to delay in injection and inaccurate dosingEvaluate degree of overdose vs ability to use ampule/syringe/needle; no specific evidence base for decision except that ampule/syringe/needle technique is delay and error prone, and autoinjector (0.15 mg) is more commonly prescribed for infants by physicians forced to choose
15 (33)0.15Yes0.15-mg autoinjector provides optimum dosePrescribe autoinjector (0.15 mg)
20 (44)0.20No0.15-mg autoinjector provides 1.3-fold underdose; 0.30-mg autoinjector provides 1.5-fold overdoseUsually prescribe 0.15-mg autoinjector, but increasing weight of child over 20 kg and high risk on the basis of clinical historyd may be considered an appropriate rationale for prescribing a 0.30-mg autoinjector
25 (55)0.25No0.15-mg autoinjector provides 1.7-fold underdose; 0.30-mg autoinjector provides 1.2-fold overdoseUsually prescribe 0.30-mg autoinjector; a small overdose in a healthy child generally carries a low risk of adverse effects compared with the risk of an underdose during anaphylaxis
>= 30 (>= 66)0.30Yes0.30-mg autoinjector provides optimum dosePrescribe autoinjector (0.30 mg)
  1. For situations in which an autoinjector containing an appropriate dose is not available, the situation is never truly acceptable, because using an epinephrine ampule/syringe/needle (see text) is prone to delay in dosing or inaccurate dosing. However, until such autoinjectors are manufactured and fixed doses of 0.05, 0.10, 0.20, and 0.25 mg are available in addition to the 0.15- and 0.30-mg doses currently available, the physician has to determine the risk versus the benefit of selecting a fixed dose that is either too low or too high and the risk/benefit of an optimal technique of administration (autoinjector) versus a technique (ampule/syringe/needle) that may be prone to delay and error in the hands of non-health care professionals.
  2. There are no studies that have provided details about risks of overdose and underdose of epinephrine in the context of first-aid treatment of anaphylaxis at most dose ranges, particularly in children who weigh less than 15 kg (33 lb). It is presumed, on the basis of limited data, that otherwise healthy children (normal cardiac status, not taking other sympathomimetics, tricyclic antidepressants, or monoamine oxidase inhibitors, etc.) would tolerate modest overdoses of epinephrine. In older children not experiencing anaphylaxis, a 1.2-fold overdose has been associated with adverse pharmacologic effects.
  3. Distributors' recommendations regarding autoinjector indications for weight/age differ from country to country, but an alternative form of epinephrine for self-injection, such as ampule/syringe/needle rather than an autoinjector, has been suggested for children who weigh less than 15 kg (33 lb). The perceived comfort and ability of families and caregivers to provide accurate doses of epinephrine for infants using an epinephrine ampule/syringe/needle should be considered in deciding the best modality and the potential degree of overdose or underdose if an autoinjector were prescribed. Although not per manufacturer's advice, it is suggested that the available evidence (error rates of ampule/syringe/needle of no dose to almost 40-fold overdose in the hands of non-health care professionals, adverse pharmacologic effects of a modest overdose in a healthy child, lack of additional fixed-dose autoinjectors) may warrant prescription of a 0.15-mg autoinjector for most healthy children who weigh 10 kg (22 lb) and more; however, individual circumstances may vary. Depending on the circumstances, provision of an autoinjector to those who weigh less than 10 kg (22 lb) may also be warranted.
  4. In addition to consideration of body weight, clinical issues that may add risk to underdosing and indicate a relative benefit for a higher dose may include 1 or more of the following: concurrent asthma; previous anaphylaxis to peanut, tree nut, milk, egg, seafood, and/or fin fish; poor access to emergency services; and/or lack of supervision.

TABLE 3 Examples of Factors That May Indicate the Need to Prescribe Epinephrine for Persons "at Risk" of Anaphylaxis18,37,38

  • Reaction history
    • Reaction to trace allergen exposure
    • Repeat exposures likely
    • Specific food triggers known to be associated with severe/fatal reactions (eg, peanut, tree nut, seafood, milk)
    • Generalized urticaria from insect venom
  • Certain comorbidities
    • Asthma
    • Use of nonselective ß-blockers
  • Additional factors
    • Initial reaction details unclear, possible anaphylaxis
    • Those living in a remote area away from medical care/access

An at-risk person can be, for example, one with a confirmed allergy to food or insect venom who has not experienced anaphylaxis. Note: a first episode of anaphylaxis can be fatal.10,11


  1. Lane R, Bolte RG. Pediatric Anaphylaxis. Pediatric Emergency Care 2007; 23:49-56.
  2. Novembre E, Cianferoni A, Bernardini R, et al. Anaphylaxis in Children: Clinical and Allergologic Features. Pediatrics 1998; 101:e8.
  3. Sampson HA, Munoz-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 2006;117:391-397.
  4. Beno SM, Nadel FM, Alessandrini EA. A Survey of Emergency Department Management of Acute Urticaria in Children. Pediatric Emergency Care 2007; 23: 862-868.
  5. Clark S, Long AA, Gaeta TJ, et al. Multicenter Study of Emergency Department Visits for Insect Sting Allergies. J Allergy Clin Immunol 2005;116:643-649.
  6. Lee JM, Greenes DS. Biphasic Anaphylactic Reactions in Pediatrics. Pediatrics 2000;106:762-766.
  7. Dibs S, Baker MD. Anaphylaxis in Children: A 5-Year Experience. Pediatrics 1997;99:e7.
  8. Davis JE, Norris RL. Allergic Emergencies in Children: The Pivotal Role of Epinephrine. Pediatric Emergency Medicine Practice. 2007;4(2):1-19.
  9. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380-384.
  10. Winbery SL, Lieberman PL. Histamine and antihistamines in anaphylaxis. Clin Allergy Immunol. 2002;17:287-317.
  11. Zemek, R.L., et al. "Systemic Review of Randomized Controlled Trial Examining Written Action Plans in Children." Arch Pediatr Adolesc Med. 2008; 162(2): 157-163.
  12. Lee JM, Greenes DS. Biphasic Anaphylactic Reactions in Pediatrics. Pediatrics 2000;106:762-766.
  13. Lieberman P, Decker W, Camargo CA, et al. SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department. Ann Allergy Asthma Immunol. 2007;98:519-523.
  14. Sicherer SH, Simons ER. Self-injectable Epinephrine for First-Aid Management of Anaphylaxis. Pediatrics 2007;119:638-646.
  15. Anaphylaxis/Allergic Reaction Action Plan (PDF)
  16. School Medication Authorization Packet (PDF)

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