Perioperative Outcomes Associated with Remimazolam Use in On-Pump Coronary Artery Bypass Grafting in Japan: A Nationwide Retrospective Cohort Study from 2020 to 2022

Remimazolam is an ultra-short-acting benzodiazepine increasingly used in cardiac anesthesia because of its favorable hemodynamic profile; however, evidence regarding its association with perioperative outcomes in cardiac surgery remains limited.We conducted a nationwide retrospective cohort study to examine whether intraoperative exposure to remimazolam was associated with perioperative mortality among patients undergoing on-pump coronary artery bypass grafting.Adult patients who underwent on-pump coronary artery bypass grafting between April 2020 and A c c e p t e d M a n u s c r i p tMarch 2022 were identified using a Japanese inpatient database.The primary outcome was perioperative mortality, defined as in-hospital death within 30 days after surgery.The association between remimazolam use and perioperative mortality was evaluated using univariable and multivariable mixed-effects logistic regression models with a random intercept for hospital.Among 8,005 patients included in the final analytic cohort, 223 received remimazolam on the day of surgery.Perioperative mortality occurred in 3.6% of patients in the remimazolam group and 4.0% in the control group.Remimazolam use was not associated with perioperative mortality in univariable analysis, and this finding remained unchanged after accounting for hospital-level variation and prespecified covariates.In this nationwide cohort, remimazolam exposure was not associated with an increased risk of perioperative mortality in patients undergoing on-pump coronary artery bypass grafting.These findings provide real-world evidence regarding the short-term safety of remimazolam and may inform the design of future prospective studies evaluating its comparative safety in cardiac surgery.