Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis

Background: A biphasic reaction is a potentially life-threatening recurrence of symptoms after initial resolution of anaphylaxis without re-exposure to the trigger. The infrequent nature of these reactions has made them difficult to study and predict. Objective: The aim of this study was to evaluate the time of onset and predictors of biphasic anaphylactic reactions. Method: Original research studies that described biphasic reactions in case series or cohort studies were included. Studies that did not describe biphasic reactions and case series with less than 2 biphasic reactions were excluded. Data sources included MEDLINE, EMBASE, Web of Science, and Scopus from inception to January 2014 and bibliographies of included articles. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous variables. Inconsistency among studies was assessed with the I² statistic. Results: Twenty-seven observational studies that enrolled 4114 patients with anaphylaxis and 192 patients with biphasic reactions were included. The median time of symptom onset was 11 (range 0.2 to 72.0) hours. Food as the inciting trigger was associated with decreased risk (pooled OR 0.62, 95% CI: 0.4 to 0.94, I² = 0%) and an unknown inciting trigger with increased risk (pooled OR 1.72, 95% CI: 1.0 to 2.95, I² = 61%). Initial presentation with hypotension (pooled OR 2.18, 95% CI: 1.14 to 4.15, I² = 79%) was also associated with the development of a biphasic reaction. Conclusion: Biphasic anaphylatic reactions were less likely among patients with food as an inciting trigger. Patients who present with hypotension or have an unknown inciting trigger may be at increased risk of a biphasic reaction. Clinicians should tailor observation periods for patients individually based on clinical characteristics.