Remimazolam dosing for gastroscopy: a randomized noninferiority trial

Abstract

Background Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. We aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. Methods This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers, between March 2021 and July 2022. A total of 1883 patients scheduled to undergo gastroscopy were randomized to 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol group. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. Results The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%, risk difference, −0.64%; 97.5% confidence interval (CI), −2.2% to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, −10.8%; 97.5% CI, −14.0% to −8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. Conclusions This trial established noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.