Remimazolam vs. propofol anaesthesia for delirium in older patients recovering from lung resections: a randomised non-inferiority trial.
INTRODUCTION Remimazolam tosylate is an ultra-short-acting benzodiazepine sedative and anaesthetic. The related drug, midazolam, is associated with delirium but it remains unclear whether remimazolam also promotes delirium. We tested the primary hypothesis that remimazolam is non-inferior to propofol for delirium in patients during the initial 3 days after lung resection surgery. Secondary outcomes were the proportion of delirium-positive assessments; duration of stay in the post-anaesthesia care unit; and hospital and Mini-mental State Examination scores at 30 days. METHODS We randomly allocated patients aged ≥ 65 y to remimazolam or propofol anaesthesia for lung resection surgery. Delirium was assessed by trained assessors blinded to trial treatment using the Confusion Assessment Method in the post-anaesthesia care unit and twice daily for 3 postoperative days. Our non-inferiority margin was a 10% absolute difference in the incidence of postoperative delirium. RESULTS The modified intent-to-treat population included 455 patients. Delirium occurred in 108/227 (48%) patients allocated to the remimazolam group and 71/228 (31%) in those allocated to the propofol group (risk ratio 1.53, 95%CI 1.21-1.94). The absolute risk difference was 16.5% (95%CI 7.7-25.3%) which considerably exceeded our non-inferiority margin; therefore, non-inferiority was not established. Emergence delirium was more frequent in patients allocated to remimazolam (105/227 (46%) vs. 64/228 (28%); risk ratio 1.65, 95%CI 1.28-2.12), whereas delirium after post-anaesthesia care unit discharge was uncommon and similar between groups (9/227 (4%) vs. 12/228 (5%); risk ratio 0.75, 95%CI 0.32-1.75). Delirium-positive assessments occurred in 129/1377 (9%) patients allocated to the remimazolam group and 102/1440 (7%) in those allocated to the propofol group (risk ratio 1.36, 95%CI 0.96-1.91). DISCUSSION Remimazolam was not non-inferior to propofol for postoperative delirium in older patients having lung resection surgery and provoked more emergence delirium.