Review explores diagnosis and management of perioperative anaphylaxis during anesthesia

Perioperative anaphylaxis is a rare, life‑threatening condition during anesthesia. The unique setting – multiple drugs, patient draping, and altered physiology – causes higher mortality than anaphylaxis elsewhere. This review covers evolving etiology, pathophysiology, atypical presentation, evidence‑based management, and prevention. Primary triggers include neuromuscular blocking agents, antibiotics, and latex, with emerging culprits (chlorhexidine, dyes, remimazolam). Diagnosis is challenging due to few cutaneous signs; cardiovascular collapse with low end‑tidal CO₂ is a key supportive indicator. Immediate management prioritizes epinephrine and aggressive fluids. Post‑event allergological testing (skin tests, tryptase/histamine) identifies the culprit. Prevention includes history‑taking, risk stratification, and latex‑free environments. Future directions: global surveillance, novel biomarkers (circulating microbiome), and simulation training.

Introduction

Incidence 1:2,000–1:20,000 procedures, but mortality higher than community anaphylaxis. Diagnosis difficult due to anesthesia‑induced changes, lack of patient feedback, and multiple triggers. This narrative review synthesizes recent evidence (2017–2025).

Pathophysiology and evolving etiology

Primarily IgE‑mediated mast cell/basophil degranulation; non‑IgE reactions also occur. Mediators cause vasodilation, capillary leak, bronchoconstriction.

• Primary triggers: NMBAs (most common), β‑lactam antibiotics, latex (declining with avoidance).

• Emerging triggers: Chlorhexidine, patent blue dye, remimazolam (case reports; cross‑reactivity with midazolam inconclusive).

• High‑risk for latex: spina bifida, chronic bladder catheterization, healthcare workers, multiple surgeries.

• Experimental: Pilot study found distinct circulating bacterial DNA (Enterobacteriaceae, Veillonellaceae) in NMBA‑allergic patients, correlating with tryptase/IgE – exploratory, needs validation.

Diagnostic challenges and advances

• Atypical presentation: Cutaneous signs rare; initial sign often cardiovascular collapse (severe hypotension), mistaken for anesthetic effects.

• Key indicator: Low ETCO₂ with hypotension – mean lowest ETCO₂ 17 mmHg in anaphylaxis vs. 32 mmHg in other causes (AUC 0.95; cutoff ~23 mmHg: 92% sensitive, 94% specific). Not specific (also hemorrhage, PE), but valuable clue.

• Bronchospasm: often severe, increased airway pressure.

• Serum tryptase: elevated in ~71% of perioperative hypersensitivity reactions.

• Plasma histamine: early, short half‑life; sample immediately and within 1–2 hours (threshold ~1.5 ng/mL at 30 min).

Immediate management and post‑event investigation

• Acute resuscitation: Stop potential triggers, 100% O₂, aggressive crystalloids, epinephrine (IM/IV titrated). Epinephrine first‑line; large volumes often needed.

• Post‑stabilization:

  • Skin testing (prick/intradermal) – cornerstone; traditionally 4–6 weeks post‑reaction.

  • Drug provocation tests – for high suspicion with negative skin tests; definitive but high risk, only in expert centers.

  • In vitro specific IgE for latex, some NMBAs, antibiotics.

Prevention and future directions

• Prevention: Meticulous preoperative history; risk stratification and labelling; latex‑free operating rooms. Premedication (antihistamines/corticosteroids) ineffective for latex.

• Future priorities:

  • International registries (e.g., NAP6) for real‑time surveillance.

  • Validate circulating microbiome as predictive biomarker.

  • Pharmacovigilance for remimazolam and other new agents.

  • Simulation‑based team training (eye‑tracking studies show experienced providers allocate attention better).

Limitations

Narrative review; evidence for emerging triggers from case reports/small series; microbiome findings preliminary; recommendations may need local adaptation.

Conclusions

Perioperative anaphylaxis is a dynamic challenge. Masked presentation requires high suspicion, guided by profound hypotension with low ETCO₂. Acute management: swift epinephrine and volume expansion. Long‑term safety relies on systematic prevention – risk‑aware evaluation, awareness of traditional and emerging triggers, and allergen avoidance. Future: surveillance, biomarkers, novel agent evaluation, and team training.

The study was recently published in the Exploratory Research and Hypothesis in Medicine.