Severe Perioperative Anaphylaxis With Positive Skin Tests to Midazolam and Rocuronium During Breast Cancer Surgery: A Case Report

Midazolam is an uncommon suspect when perioperative anaphylaxis follows the administration of several drugs at induction.We report a 50-year-old woman with allergic asthma who, within minutes of induction for breast cancer surgery, developed hypotension, tachycardia, generalized erythema, severe bronchospasm, and desaturation (peripheral oxygen saturation nadir 70%).Ceftriaxone 2 g had been given before induction with midazolam 2 mg, propofol 100 mg, fentanyl 100 µg, and rocuronium 40 mg; sevoflurane was used for maintenance.The first arterial blood gas showed a pH of 7.164, a partial pressure of arterial carbon dioxide (PaCO 2 ) of 69.5 mmHg, and a partial pressure of arterial oxygen (PaO 2 ) of 44.1 mmHg.She was treated with 100% oxygen, ventilatory support, intravenous epinephrine, inhaled and intravenous salbutamol, corticosteroids, and chlorphenamine.Surgery was postponed, and she required overnight intensive care, during which rocuronium was re-administered by infusion without a renewed reaction.Serial videolaryngoscopy showed laryngeal edema that resolved before extubation on day 1.Skin tests on day 14 were positive to rocuronium at 0.05 mg/mL and midazolam at 0.5 mg/mL and negative to propofol, fentanyl, sevoflurane, and latex; tryptase was not measured.The midazolam concentration was 10 times the European Academy of Allergy and Clinical Immunology (EAACI) maximum non-irritant intradermal concentration (0.05 mg/mL), so an irritant false-positive result cannot be excluded, and ceftriaxone was not specifically tested.On day 28, general anesthesia with propofol, fentanyl, remifentanil, and sevoflurane, avoiding midazolam, neuromuscular blocking agents, and beta-lactams, was uneventful.The case highlights the need to include benzodiazepines in perioperative allergy work-ups, to use validated test concentrations and timing, to measure tryptase, and to avoid all suspected agents after the reaction.