Suspected remimazolam formulation-associated peri-induction anaphylaxis: two cases highlighting diagnostic complexity - Two case reports -

Background: Reports of remimazolam formulation-associated anaphylaxis are increasing as its use expands. Between 2023 and 2025, we identified two severe reactions among 1,592 patients who received remimazolam at our institution. Case: A 65-year-old man (American Society of Anesthesiologists physical status [ASA PS] III) with end-stage renal disease developed profound hypotension without cutaneous signs after induction with 10 mg of remimazolam and peri-induction cefazedone administration. Surgery was cancelled due to persistent hypotension. Serum tryptase measured 6 h after the event was 38.0 μg/L; however, delayed skin testing was negative. Subsequent propofol-based anesthesia without cefazedone re-administration was uneventful. A 50-year-old woman (ASA PS I) developed hypotension and facial flushing within 2 min of receiving 10 mg of remimazolam. Although serum tryptase levels remained within the normal range (5.3 and 5.1 μg/L), delayed skin testing for remimazolam was positive. Conclusions: Diagnosis of remimazolam formulation-associated hypersensitivity may remain inconclusive when based on a single diagnostic test. Accurate evaluation requires integrating timed tryptase, delayed skin testing, and careful evaluation of exposure history.