Biphasic Anaphylaxis in the Emergency Department

Date First Published:
August 31, 2019
Last Updated:
August 31, 2019
Report by:
Catherine Cooley Hixson MD, Todd Chassee MD, EM Senior Resident, EM Faculty (Spectrum Health/Michigan State University Emergency Medicine Residency Program)
Search checked by:
Jeffrey Jones, Spectrum Health/Michigan State University Emergency Medicine Residency Program
Three-Part Question:
What is the [risk of a biphasic reaction] in [patients with acute anaphylaxis] who have been [successfully treated with resolution of symptoms].
Clinical Scenario:
26-year-old man presents to the emergency department (ED) with concern for recent perioral swelling, wheezing, nausea and urticaria after bee envenomation. He has a known allergy to bees and was able to administer 1 dose of intramuscular epinephrine. He arrived to your ED within thirty minutes and his symptoms of anaphylaxis are largely resolved. You consider how long to monitor the patient in the ED.
Search Strategy:
Medline 1966-08/19 using PubMed, Cochrane Library (2019), and Embase.
Search Details:
[(exp anaphylaxis) AND (exp biphasic reaction)]. Limit to English language.
Outcome:
38 studies were identified; two recent systematic reviews addressed the clinical question.
Relevant Paper(s):
Study Title Patient Group Study type (level of evidence) Outcomes Key results Study Weaknesses
Biphasic anaphylaxis: A review of the literature and implications for emergency management. Pourmand A, Robinson C, Syed W, Mazer-Amirshahi M. Aug-18 United States 155 studies of patients in ED setting with anaphylaxis Systematic review Time to biphasic reaction Wide range from 1 to 72 hours, with a mean greater than 8 hours; most occurrences happening outside the recommended 4 to 6 hour period Limited evidence on symptoms related to biphasic reaction, limited evidence for corticosteroid use with no RCT regarding this treatment and biphasic reactions
Rate of occurrence of biphasic anaphylaxis Older studies suggested a biphasic reaction can occur in up to 20% of patients. Larger, more recent studies suggest the incidence is more likely about 4%. One study found the incidence to be 2.2% in the pediatric population.
Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis Kim TH, Yoon SH, Hong H, Kang HR, Cho SH, Lee SY. Feb-19 Republic of Korea Adult patients with anaphylaxis and biphasic anaphylactic reactions Meta-Analysis of 12 studies Pooled negative predictive value for a biphasic reaction The pooled NPV for biphasic anaphylactic reaction at 1 hour was 95.0%, and 97.3% at greater than 6 hours. Limited studies and rarity of disease may lead to selection bias, ambiguous definition of biphasic reaction, features of anaphylaxis not described
Author Commentary:
Biphasic anaphylaxis is an anaphylactic episode followed by an asymptomatic period with return of anaphylactic symptoms in the absence of further exposure to the triggering antigen. The traditional recommended ED observation time is 4-6 h after complete resolution of symptoms for every anaphylaxis patient. However, there is limited data to identify predisposing factors to recurrent reactions, and more recent data suggests this clinical entity is rare (4%) and can occur at any time between 10 minutes to 6 days. Consider sending the ED patient home with injectable epinephrine (epi pen) and steroids after a 1-hour observation period.
Bottom Line:
Biphasic anaphylaxis is a rare clinical entity with low morbidity and mortality. A 1-hour observation period has been shown to achieve a 95.0% negative predictive value (NPV), with little added clinical benefit when extending the observation period.

References:
  1. Pourmand A, Robinson C, Syed W, Mazer-Amirshahi M.. Biphasic anaphylaxis: A review of the literature and implications for emergency management.
  2. Kim TH, Yoon SH, Hong H, Kang HR, Cho SH, Lee SY.. Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis