Severe initial presentation (eg, hypotension or severe respiratory compromise)
Delayed time to first epinephrine treatment (eg, >60 minutes)
Need for >1 dose of epinephrine
Less certain (implicated in some studies but not others)
Unknown trigger
Possible ongoing exposure to trigger: sustained-release medications or depot medications, foods
A prolonged interval (eg, hours) between contact with the trigger and the start of initial symptoms
Treatment with antihistamines or glucocorticoids without epinephrine
The table lists possible risk factors for biphasic anaphylaxis based on several meta-analyses and studies. Refer to UpToDate topics on anaphylaxis for recommendations on duration of observation in patients with anaphylaxis and one or more risk factors.
References:
Shaker MS, Wallace DV, Golden DBK, et al. 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.
Lee S, Bellolio MF, Hess EP, et al. Time of onset and predictors of biphasic anaphylactic reactions: A systematic review and meta-analysis. J Allergy Clin Immunol Pract 2015; 3:408.
Kraft M, Hofmeier KS, Ruëff F, et al. Risk factors and characteristics of biphasic anaphylaxis. J Allergy Clin Immunol Pract 2020; 8:3388.
Liu X, Lee S, Lohse CM, et al. Biphasic reactions in emergency department anaphylaxis patients: A prospective cohort study. J Allergy Clin Immunol Pract 2020; 8:1230.
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