Clinical bottom line
Perioperative anaphylaxis remains a rare but potentially life-threatening complication during surgery, requiring rapid recognition and management to prevent morbidity and mortality. Advances in diagnostic strategies, including detailed allergologic workup and improved identification of culprit agents such as neuromuscular blocking agents and gelatin-containing products, have enhanced post-event evaluation. Emerging consensus emphasizes multidisciplinary perioperative protocols, early epinephrine administration, and tailored avoidance strategies to reduce recurrence risk. However, diagnostic challenges and therapeutic hesitancy, especially in special populations like pregnant patients, persist and warrant ongoing clinician vigilance.
What the evidence shows
Perioperative anaphylaxis is characterized by sudden onset of systemic hypersensitivity reactions triggered by agents administered during anesthesia or surgery. Common culprits include neuromuscular blocking agents, antibiotics, and less frequently, gelatin-containing blood products or colloids (Brockow, 2014; Volcheck et al., 2019). The clinical presentation can be masked by anesthesia effects, complicating prompt recognition.
Diagnostic workup after an event involves skin testing, specific IgE assays, and detailed patient history to identify the offending agent. Brockow (2014) highlights dilemmas in allergy diagnosis due to cross-reactivity and false negatives, underscoring the need for comprehensive allergologic evaluation. Gelatin anaphylaxis, though rare, has been increasingly recognized as a cause of perioperative reactions, with case reports and series emphasizing the importance of considering gelatin-containing products in differential diagnosis (Raveendran et al., 2017; CME Exam, 2017).
Management prioritizes immediate intramuscular epinephrine administration, airway support, and hemodynamic stabilization. Volcheck et al. (2019) provide practical guidance on acute management and emphasize multidisciplinary coordination between anesthesiologists, allergists, and surgeons. In pregnancy, anaphylaxis poses unique challenges; Tan et al. (2022) and Tanno et al. (2026) discuss diagnostic blind spots and epinephrine hesitancy due to fetal concerns, advocating for prompt treatment to optimize maternal and fetal outcomes.
Recent consensus recommendations on intravenous iron administration also address perioperative hypersensitivity, recommending protocols to minimize adverse events and improve patient safety (Saal-Bauernschubert et al., 2026).
Caveats and uncertainty
Despite advances, perioperative anaphylaxis diagnosis remains challenging due to overlapping clinical features with other intraoperative complications and limitations of current diagnostic tests. False negatives in skin testing and variability in specific IgE assays can lead to missed or incorrect culprit identification (Brockow, 2014). The rarity of gelatin anaphylaxis limits large-scale data, and most evidence derives from case reports or small series, necessitating cautious interpretation (Raveendran et al., 2017).
Management in pregnancy is complicated by limited data and concerns about epinephrine safety, although current evidence supports its use despite hesitancy (Tan et al., 2022; Tanno et al., 2026). Additionally, standardized perioperative protocols vary widely across institutions, and implementation barriers remain.
How this may change practice
Clinicians should maintain a high index of suspicion for perioperative anaphylaxis, especially when unexplained hemodynamic instability or cutaneous signs occur intraoperatively. Early intramuscular epinephrine administration must be prioritized, including in pregnant patients, to improve outcomes. Post-event referral to allergy specialists for comprehensive evaluation is essential to identify triggers and guide future anesthetic planning.
Awareness of less common triggers such as gelatin-containing products should be increased, with careful review of all perioperative agents administered. Institutions may consider adopting standardized protocols incorporating multidisciplinary collaboration for prevention, recognition, and management of perioperative anaphylaxis.
Education efforts addressing epinephrine hesitancy in pregnancy and improving diagnostic accuracy through combined testing modalities may further enhance care quality. Finally, integration of emerging consensus on intravenous iron hypersensitivity management may reduce perioperative adverse events in relevant populations.