Anaphylaxis: It’s all about the Epi

The most recent recommendations from The Joint Task Force on Practice Parameters for Allergy & Immunology strongly emphasize the administration of intramuscular epinephrine into the anterolateral thigh as the first-line treatment for anaphylaxis. Studies have shown that there is a faster onset of action and peak concentration compared to deltoid or subcutaneous administration. Because of potential side effects, intravenous administration should be limited to patients who are cardiovascularly unstable.

Antihistamines (e.g., diphenhydramine, famotidine, cetirizine, loratadine, or fexofenadine) are considered second line therapy since they are slow on onset and do not effectively treat symptoms such as bronchospasm or hypotension. Steroids (e.g., prednisolone, prednisone, methylprednisolone, or dexamethasone) were thought to minimize the risk of a late phase reaction; however meta-analyses have not definitively shown them to be helpful. Neither should be given before or in place of epinephrine.

In the ED, treatment for anaphylaxis includes administration of epinephrine intramuscularly (if not done so prior to arrival) and treatment of the individual symptoms. For example, hypotension may require IV fluids and/or vasopressor support; bronchospasm may require use of inhaled beta-agonists; nausea and vomiting may need anti-emetics. Oftentimes, as noted above, antihistamines +/- steroids are given.

Antihistamines can be helpful in treating cutaneous symptoms such as hives and itching. Second generation H1 antihistamines (e.g., cetirizine [PO or IV]) are preferred as they are less sedating, have fewer anticholinergic effects, and longer duration of action.

 If the child stabilizes quickly, (s)he will be monitored in the ED for several hours for recurrence of symptoms: at least 2 hours after the dose of epinephrine and at least 4 hours in the ED (6-8 hours if there was evidence of respiratory or cardiovascular compromise). CHOA’s ED Anaphylaxisis guidelines recommends observing for 4 hours. If symptoms persist, recur, or worsen, multiple IV fluids boluses or epinephrine doses are needed, or if there is a history of severe asthma or biphasic reactions, the child will most likely be admitted for inpatient observation. 

If the child remains stable, then education on allergic reactions and how to use an Epinephrine autoinjector will be done prior to discharge. In addition, prescriptions for an Epinephrine autoinjector +/- other adjunctive medications (i.e., antihistamines, bronchodilators, or steroids) will be given. These children need close follow up with their primary care physician within 24 hours, as well as follow up in 3-4 weeks with an allergist. A tryptase level, drawn within _8_ hours of symptom onset, may be helpful during the follow-up visit with an allergist as it has been shown to have a positive predictive value of > 90%.

Some great resources include the following websites:

Joint Task Force on Practice Parameters for Allergy & Immunology (

American Academy of Allergy Asthma & Immunology (

American College of Allergy, Asthma & Immunology (

Food Allergy Research & Education (

World Allergy Organization (

To CLaim CME for this article, click Here, but please read the Anaphylaxis Article FIRST!


The Joint Task Force on Practice Parameters for Allergy & Immunology. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020; 145:1082-123. (

Cardona et al. World Allergy Organization Anaphylaxis Guidance 2020. World Allergy Organization Journal (2020) 13:100472. (

Campbell RL, Kelso JM. Anaphylaxis: Emergency treatment. UpToDate accessed September 1, 2012.

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