OBJECTIVES: To evaluate whether remimazolam besylate could provide noninferior sedation to dexmedetomidine in patients under mechanical ventilation (MV) in the ICU.
DESIGN: A multicenter, single-blind, randomized, noninferiority trial.
SETTING: Fifteen ICUs across China between October 2021 and November 2023.
PATIENTS: Adults under endotracheal intubation MV who were expected to require sedation for 8-48 hours.
INTERVENTIONS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: Remimazolam besylate could provide noninferior sedation as dexmedetomidine with a lower risk of bradycardia for 48 hours in mechanically ventilated patients in the ICU.
| Discipline Area | Score |
|---|---|
| Intensivist/Critical Care |  |
| Anesthesiology | |
| Respirology/Pulmonology |  |
This well conducted RCT of 299 patient in 15 ICUs across China, compared remimazolam (R) vs dexmedetomidine (D) for sedation in mechanically ventilated (MV) patients at 48hr. Patient and assessors were blinded with well-matched baseline demographics. They found no difference in the primary outcome of times observed in the target RASS (-2 to +1) in the first 48hr 82.6% vs 83.2% (p = 0.663) for R vs D, respectively. There was no difference in need for rescue propofol sedation, hypotension, delirium, length of MV, ICU or hospital stay. There was significantly greater incidence of bradycardia in the D group (4.7 vs 0.7%). There are a few limitations that will be useful to consider in future studies: The mean APACHE 2 score was 14, with patients suffering limited organ failures, notably liver and renal. Stopping at 48hr limits the applicability to longer-term sedation and R has no formal sedation dose for MV patients. The authors should be congratulated for this study.
Good study that provides more options for day-to-day critical care.
Non-inferiority trial of a non-patient-centered outcome (RASS in goal/RASS comparing remimazolam vs dexmedetomidine). It was unclear why dexmedetomidine was selected as a comparator. This trial is unlikely to inform practice.
