Biphasic Reactions in Emergency Department Anaphylaxis Patients: A Prospective Cohort Study

J Allergy Clin Immunol Pract. 2020 Apr;8(4):1230-1238. doi: 10.1016/j.jaip.2019.10.027. Epub 2019 Nov 6.


Background: Biphasic reaction rates and potential associated risk factors are not well understood.

Objective: To evaluate biphasic reaction rates and associated risk factors.

Methods: We prospectively enrolled patients with anaphylaxis at 2 Midwestern academic emergency departments (EDs). We gathered data using patient and ED provider surveys and a structured health record review. Biphasic reaction rates and clinically significant biphasic reaction rates, defined as recurrent reactions that met anaphylaxis diagnostic criteria or were treated with epinephrine, were calculated. Characteristics associated with biphasic reactions were assessed with logistic regression and reported with odds ratios (ORs) and 95% CIs.

Results: Of 430 ED anaphylaxis visits, 31 (7.2%) patients had biphasic reactions; 22 (5.1%) had clinically significant biphasic reactions. The median time from anaphylaxis onset to first epinephrine dose was longer for patients with biphasic (78 minutes) than uniphasic courses (45 minutes) (P = .005). A biphasic course was associated with an ED setting of first epinephrine dose (OR, 3.72; 95% CI, 1.36-10.14) and a delay of more than 30 minutes from symptom onset to first epinephrine dose (OR, 3.39; 95% CI, 1.13-10.18), and was inversely associated with arrival by ambulance (OR, 0.18; 95% CI, 0.05-0.61). A clinically significant biphasic reaction was associated with an ED setting of first epinephrine dose (OR, 3.32; 95% CI, 1.08-10.25) and inversely associated with arrival by ambulance (OR, 0.08; 95% CI, 0.01-0.61).

Conclusions: Biphasic reactions and clinically significant biphasic reactions occurred in 7.2% and 5.1% of ED anaphylaxis patients, respectively. Delayed epinephrine administration was associated with biphasic reactions.

Keywords: Anaphylaxis; Biphasic reaction; Emergency department; Epinephrine.

MeSH terms

  • Anaphylaxis* / diagnosis
  • Anaphylaxis* / drug therapy
  • Anaphylaxis* / epidemiology
  • Emergency Service, Hospital
  • Epinephrine / therapeutic use
  • Humans
  • Odds Ratio
  • Prospective Studies


  • Epinephrine