Remimazolam-Induced Anaphylaxis After Spinal Anesthesia: A Case Report and Literature Review

Perioperative anaphylaxis, though rare, is a potentially life-threatening complication. While antibiotics and neuromuscular blocking agents are common triggers, benzodiazepine-induced reactions have been considered uncommon. Remimazolam, a novel benzodiazepine sedative, has gained widespread use in Korea due to its rapid onset, short recovery, hemodynamic stability, and availability of flumazenil. However, increasing utilization has coincided with rising reports of hypersensitivity. We report the case of a 62-year-old female undergoing contralateral total knee replacement under spinal anesthesia. Continuous remimazolam infusion was initiated, but within ten minutes the patient developed chest discomfort followed by abrupt hypotension and oxygen desaturation, requiring urgent conversion to general anesthesia. Following a remimazolam bolus and rocuronium administration, sudden cardiac arrest occurred. Return of spontaneous circulation (ROSC) was achieved after approximately 28 min of cardiopulmonary resuscitation with a cumulative intravenous epinephrine dose of approximately 17 mg, and veno-arterial extracorporeal membrane oxygenation (ECMO) was required. Post-ROSC transesophageal echocardiography demonstrated a transient anteroseptal regional wall motion abnormality; subsequent coronary angiography demonstrated no significant coronary disease, and computed tomography pulmonary angiography was negative for embolism, leaving acute hypersensitivity as the most plausible mechanism. Acute serum tryptase was elevated at 11.6 µg/L and normalized to 3.4 µg/L (the patient's individual baseline) prior to discharge, satisfying the World Allergy Organization (WAO) criterion. A skin prick test performed four weeks later was positive for remimazolam and negative for rocuronium and the other coadministered agents. An expanded multi-database literature review identified 16 prior cases of remimazolam-induced anaphylaxis. Most described cardiovascular collapse as the predominant manifestation. To our knowledge, based on available literature, this is among the first reports of remimazolam-induced anaphylaxis occurring in the setting of high spinal anesthesia with sympathetic blockade. Vigilance and adherence to established anaphylaxis management guidelines are essential.