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.

Remimazolam for sedation in gastrointestinal endoscopy: A comprehensive review

“…Some studies, such as those conducted by Chen et al [ 18 ], Zhang et al [ 55 ], Cao et al [ 56 ], and Xiao et al [ 57 ], reported faster recovery times in the Remimazolam compared to Propofol group. However, other studies, such as those conducted by Hu et al [ 51 ], Dong et al [ 58 ], and Zhu et al [ 59 ] reported longer recovery times in the Remimazolam compared to the Propofol cohort. One study by Guo et al [ 39 ] found no significant difference in recovery times between the two sedatives for GI endoscopy, particularly in elderly patients.…”

“…In the upper and lower GI endoscopic procedures, Remimazolam has shown excellent efficacy. In the RCT by Zhu et al [ 59 ], it was established that 0.2 mg/kg dose of Remimazolam provided adequate and non-inferior sedation as compared to propofol (1.5 mg/kg) in upper GI endoscopy with a superior safety profile. Furthermore, Ye et al [ 80 ] also noted that the ED95 of 0.2039 mg/kg (95%CI 0.1753-0.3896) for Remimazolam was consistent with previous published literature.…”

“…As patients undergoing ERCP need to be in a prone to semi-prone position for a prolonged period, it causes physiological changes in hemodynamics and respiration leading to challenges in management of the respiratory tract during the procedure[ 83 ]. Hence, Remimazolam can be considered as an alternative to the traditional sedating agents such as propofol due to its lower rates of respiratory depression[ 59 , 84 ]. Tan et al [ 84 ] calculated the ED50 and ED95 of Remimazolam for adequate sedation in ERCP, which were found to be 0.196 mg/kg (95%CI: 0.187–0.206 mg/kg) and 0.239 mg/kg (95%CI: 0.221–0.297 mg/kg), respectively.…”