Biphasic anaphylaxis: A review of the literature and implications for emergency management

Am J Emerg Med. 2018 Aug;36(8):1480-1485. doi: 10.1016/j.ajem.2018.05.009. Epub 2018 May 9.


Background: The biphasic reaction is a feared complication of anaphylaxis management in the emergency department (ED). The traditional recommended ED observation time is 4-6 h after complete resolution of symptoms for every anaphylaxis patient. However, there has been great controversy regarding whether this standard of care is evidence-based.

Methods: Articles were selected using a PubMed, MEDLINE search for the keywords "biphasic anaphylaxis", yielding 155 articles. Articles were filtered by English language, and the keyword biphasic in the title. Case reports and case series were excluded, narrowing to 33 articles. Then, articles were filtered by relevance to the ED setting, and studies conducted in outpatient clinic settings were excluded, narrowing the search to 16 articles. All remaining articles were reviewed and findings were discussed.

Results: The reported mean time to onset between the resolution of initial anaphylaxis and biphasic reaction ranges widely by study from 1 to 72 h with the majority of studies reporting the mean time to onset >8 h. A delay between anaphylaxis symptom onset and administration of epinephrine of 60-190 min was reported to correlate with biphasic anaphylaxis in three studies. Anaphylaxis requiring >1 dose of epinephrine to achieve symptom resolution was also reported to correlate with biphasic reactions in two studies. No definitive conclusions about the role of corticosteroids in preventing biphasic reactions can be made at this time however; a couple small studies have shown that they may decrease the incidence of biphasic reactions. Additional risk factors correlated with biphasic reaction vary widely between studies and the generalizability of these risk factors is questionable.

Conclusions: There is a need for further research to identify true risk factors associated with biphasic anaphylaxis and to clearly define the role of corticosteroids in biphasic reactions. However, given the low incidence and rare mortality of biphasic reactions, patients who receive epinephrine within one hour of symptom onset and who respond to epinephrine with rapid and complete symptom resolution can probably be discharged from the ED with careful return precautions and education without the need for prolonged observation.

Keywords: Allergic reaction; Anaphylaxis; Biphasic reaction; Corticosteroids; Epinephrine.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Anaphylaxis / drug therapy*
  • Anaphylaxis / physiopathology*
  • Emergency Service, Hospital / statistics & numerical data
  • Epinephrine / therapeutic use*
  • Humans
  • Recurrence
  • Risk Factors
  • Time Factors


  • Adrenal Cortex Hormones
  • Epinephrine