Remimazolam Besylate Versus Dexmedetomidine As a Sedative in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-blinded, Randomized, Noninferiority Trial.

Abstract

To evaluate whether remimazolam besylate could provide noninferior sedation to dexmedetomidine in patients under mechanical ventilation (MV) in the ICU. A multicenter, single-blind, randomized, noninferiority trial. Fifteen ICUs across China between October 2021 and November 2023. Adults under endotracheal intubation MV who were expected to require sedation for 8-48 hours. Three hundred fourteen patients were randomly assigned at a 1:1 ratio to the remimazolam besylate or dexmedetomidine group. Analgesia was provided via a continuous IV infusion of remifentanil at 1.2-9.0 µg/kg/hr. Remimazolam besylate or dexmedetomidine was administered IV at an initial loading dose of 0.1 mg/kg followed by a maintenance dose of 0.10-0.30 mg/kg/hr or at an initial loading dose of 0.20 µg/kg followed by a maintenance dose of 0.2-0.70 µg/kg/hr to achieve the targeted sedation range on the Richmond Agitation-Sedation Scale of -2 to +1. Of the 314 patients enrolled, 299 completed the study. The sedation efficacy rates, as the primary endpoint, were 82.6% and 83.2% in remimazolam besylate and dexmedetomidine groups, respectively, in the per-protocol set (PPS), whereas the rate was 72.9% in both groups in the intention-to-treat (ITT) set. The noninferiority margin was set as 10%, and the lower limits of the two-sided 95% CI for the intergroup difference were -3.0% and -2.6% in the PPS and ITT sets, respectively. The dexmedetomidine group had a higher incidence of bradycardia than the remimazolam besylate group (4.7% vs. 0.7%; p = 0.029), whereas no intergroup differences were noted for the remaining secondary endpoints and adverse events. Remimazolam besylate could provide noninferior sedation as dexmedetomidine with a lower risk of bradycardia for 48 hours in mechanically ventilated patients in the ICU.