BACKGROUND: Midazolam and propofol are frequently used for procedural sedation. Remimazolam may provide a more controllable sedation with fewer adverse effects. OBJECTIVE: To assess the sedation success rate and respiratory and cardiovascular complications of remimazolam versus placebo and other sedatives in adults undergoing procedural sedation. DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses, trial sequential analyses (TSA), and GRADE evaluations of the certainty of evidence. DATA SOURCES: We searched Medline, Embase, CENTRAL, BIOSIS, CINAHL, and Web of Science Core Collection from their inception to 22 June 2024. ELIGIBILITY CRITERIA: RCTs allocating participants undergoing procedural sedation to remimazolam versus placebo or any active comparator. RESULTS: We included 63 trials randomising 13 953 participants. All included trial results were judged to be at high risk of bias. The sedation success rate was similar with remimazolam versus active comparators, relative risk (RR) 1.04, [97.5% confidence interval (CI), 0.96 to 1.14
TSA-adjusted CI, 0.95 to 1.18], P = 0.26, GRADE: very low. Subgroup analyses indicated that remimazolam versus midazolam increased sedation success rate, while the risks were similar with remimazolam versus comparators. Remimazolam versus active comparators decreased the risk of respiratory complications, RR 0.47, (97.5% CI, 0.36 to 0.61
TSA-adjusted CI, 0.35 to 0.61), P <
0.01
and cardiovascular complications, RR 0.46, (97.5% CI, 0.37 to 0.56
TSA-adjusted CI, 0.38 to 0.57), P <
0.01. Subgroup analyses indicated that remimazolam versus propofol reduced respiratory and cardiovascular complications, while the risks were similar versus midazolam. CONCLUSION: Remimazolam seems to provide a similar sedation success rate as other active comparators (propofol, ciprofol, midazolam, dexmedetomidine, etomidate), although subgroup analyses indicated that remimazolam increased sedation success rate compared to midazolam. Remimazolam compared to propofol may decrease the risk of respiratory and cardiovascular complications. The certainty of the evidence was very low to low, and firm conclusions could not be drawn.