Sequential use of midazolam and Remimazolam besylate for sedation in critically ill, mechanically ventilated patients: a randomized controlled study

Abstract

Background: Previous research has indicated that the administration of short-acting sedatives prior to weaning from mechanical ventilation is linked to a more rapid recovery and extubation process, as well as to lower intensive care unit (ICU) treatment expenses. The present study endeavors to assess the efficacy and safety of the sequential application of remimazolam besylate compared with midazolam before weaning from mechanical ventilation. Methods: This multicenter, randomized controlled trial was conducted across medical and surgical ICU within a tertiary, academic medical center. The study population comprised critically ill, mechanically ventilated adult patients. Candidates anticipated to be ready for weaning from the ventilator within 12 hours were subjected to a Spontaneous Breathing Trial (SBT) safety screen, only those who successfully passed this assessment were considered for inclusion in the final phase of the study for subsequent randomization. Patients were randomized to either group M, where the sedative regimen was transitioned to midazolam, or to group R, which involved a switch to remimazolam. Sedative dosages were titrated to achieve the targeted Richmond Agitation-Sedation Scale (RASS) score range of -3 to 0. The primary endpoint of the stud was the time to extubation. Results: A total of 435 patients underwent screening, with 306 patients being randomized, and 272 patients ultimately included in the analysis, comprising 132 patients in group M and 140 patients in group R. Patients in group R maintained a lighter level of sedation compared to those in group M. And patients in group R demonstrated a significantly earlier recovery (P<0.05) and extubation (P<0.05) at the same RASS score before the cessation of sedatives. A higher prevalence of agitation was observed in group M as opposed to group R (20.45% vs. 8.57%, P=0.005). However, there was no notable difference in the incidence of delirium between the two groups. Conclusions: In critically ill, mechanically ventilated patients receiving remimazolam besylate exhibited a shorter time to recovery and extubation before weaning from the ventilator, coupled with a diminished incidence of agitation. Trial registration: ChiCTR 2200065048. Registered October 22. 2022