Biphasic anaphylaxis remains an under-recognized threat who’s timing directly conflicts with conventional 2–4-hour ED observation practices. This narrative review synthesizes evidence published between 2015 and 2025, sourced from PubMed, MEDLINE, and major allergy/immunology society guidelines. A narrative synthesis was chosen due to heterogeneity in definitions and outcome reporting across studies. The analysis focuses on the evolution of risk factors, diagnostic criteria, and the performance of time-based observation strategies to inform contemporary ED disposition policies. Over the past decade, a paradigm shift has occurred, moving away from fixed observation durations toward risk-stratified approaches. Major practice parameters from the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI) now emphasize individualized observation based on the severity of the initial event. More than half of clinically significant biphasic events occur after four to six hours, indicating that traditional observation windows are insufficient for many patients. Key predictors of biphasic reactions consistently identified include a severe initial presentation (e.g., hypotension, hypoxia), the need for more than one dose of epinephrine, and a delay in initial epinephrine administration. Recent meta-analytic work has quantified the performance of observation cut-offs, demonstrating a pooled negative predictive value (NPV) of ~ 95% at 1 h, rising to ~ 97% at ≥ 6 h, and > 98% for observation periods exceeding 8–12 h. This suggests that observation periods under 6 h may be insufficient for many patients, aligning with UK National Institute for Health and Care Excellence (NICE) guidance, which typically recommends 6–12 h of observation, particularly when risk factors are present. EDs should adopt risk-stratified observation pathways. A low-risk pathway (e.g., rapid and complete resolution after a single epinephrine dose, known food trigger, no cardiovascular or respiratory compromise) may permit shorter observation if coupled with a robust discharge education bundle. Conversely, a high-risk pathway (e.g., delayed or ≥ 2 epinephrine doses, hypotension/hypoxia, non-food/unknown trigger, or comorbidities like asthma or beta-blocker use) warrants prolonged observation (≥ 6 h) or hospital admission. Future research should prioritize prospective, multicenter ED registries to precisely document the timing of treatment-requiring relapses and further refine the dose-response relationship between observation duration and the risk of missed biphasic events, stratified by age and trigger. Not applicable.
Abouelmagd et al. (Sat,) studied this question.