BACKGROUND: To compare the POD rates in patients undergoing non-cardiac surgery who received remimazolam perioperatively versus placebo or other sedatives. METHODS: We systematically searched four major databases (Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed) for relevant randomized controlled trials (RCTs) up to July 11, 2024. Literature quality evaluation was used the bias risk table in Review Manager 5.4. The primary outcome of interest was POD, and secondary outcomes were the hypotension risk, bradycardia and, nausea and vomiting. RESULTS: Across 11 trials involving 1985 participants, we recorded 309 cases of POD during follow-up. In trials where the control group received saline, remimazolam decrease the risk of POD significantly by 70% (RR 0.30, 95% CI [0.19, 0.46]
p <
0.00002). Statistical analysis did not show significant difference in the risk of POD between the remimazolam group and the groups receiving either dexmedetomidine (RR 1.23 [0.64, 2.37]
p = 0.53) or propofol (RR 0.83 [0.60, 1.16]
p = 0.28). Regarding adverse events, remimazolam significantly reduces the morbidity of hypotension compared to dexmedetomidine (RR 0.25 [0.10, 0.65]
p = 0.004) and propofol (RR 0.45 [0.33, 0.60]
p <
0.00002). In addition, there were no significant differences in the incidence of bradycardia (RR 0.85
95% CI [0.34-2.12], p = 0.72) and nausea and vomiting (RR 1.06
95% CI [0.74-1.51], p = 0.77) between remimazolam and the control group. CONCLUSIONS: During the perioperative period, using remimazolam can lower POD risk after surgery for patients who had non-cardiac surgery, but remimazolam does not work better than dexmedetomidine or propofol. Compared with the dexmedetomidine and propofol, remimazolam also has apparent advantages in preventing intraoperative hypotension.