Question: In patients with anaphylaxis who do not experience resolution of symptoms after receiving the first dose of epinephrine (P), does administering a second dose of epinephrine (I) compared to not administering a second dose of epinephrine (C) change outcomes (O)?

Results: Ten observational studies were identified, all of which were categorized as very low quality due to risk of bias and confounding variables.

Outcomes: Nine studies showed benefit from repeat administration of epinephrine, while a single study demonstrated no difference in resolution of symptoms when comparing one dose versus two doses. None of these studies specifically addressed adverse effects or complications from multiple epinephrine doses.

Discussion: Despite limited data, the benefit of resolution of life-threatening symptoms, including compromised airway, difficulty breathing, and hemodynamic collapse, appears to outweigh the potential risks. While a time frame for administration of a second dose was not addressed by the current literature review, previous studies suggest 10 to 15 minutes between the two doses. There are reports in the literature of adverse effects following incorrect doses or routes of administration. Auto-injectors may reduce the occurrence of these adverse events.

Recommendation: A second dose of epinephrine should be administered to patients who are experiencing severe anaphylaxis and who have not had a resolution of symptoms after the initial dose (weak recommendation, very-low-quality evidence).

Note from Dr. Mell: While the data only weakly support the practice in the prehospital environment, this is the standard practice in emergency medicine. There’s no reason to withhold a second epinephrine dose (if needed) outside of the hospital.