Systematic review and meta-analysis shows remimazolam versus non-remimazolam anesthesia and delirium risk

BackgroundThe association between remimazolam, a novel ultra-short-acting benzodiazepine, and the risk of postoperative delirium (POD) and emergence delirium (ED) remains controversial, particularly following prolonged infusion.MethodsPUBMED, EMBASE, WEB OF SCIENCE and the Cochrane Library electronic databases were searched up to December 10, 2025. The primary outcome was the incidence of delirium. Secondary outcomes included postoperative nausea and vomiting (PONV), respiratory depression after extubation, extubation time and length of hospital stay. Subgroup and meta-regression analyses were conducted to assess clinical and methodological sources of heterogeneity in intervention effect, including age, type of surgery, assessment methods of delirium, depth of anesthesia monitoring, the use of flumazenil as an antagonist for remimazolam.ResultsA total of 30 trials were included, consisting of 25 RCTs, 4 retrospective studies and a prospective cohort study. The incidence of delirium was 11.4% (312/2734) in the remimazolam group and 15.2% (429/2827) in the non-remimazolam group, showing no significant difference (RR = 0.81; 95% confidence interval (CI), 0.63–1.05, p = 0.11) between groups. Subgroup analysis by anesthesia type, however, revealed a significant effect modification. In patients undergoing general anesthesia, remimazolam was associated with a 23% reduction in the risk of delirium (RR = 0.77, 95% CI: 0.60–1.00, p = 0.05). When viewed in terms of this dichotomy, no significant difference was observed in 22 studies evaluating the incidence of POD between remimazolam group (13.1%, 295/2260) and non-remimazolam group (16%, 390/2431) (RR = 0.93; 95% CI, 0.76–1.15, p = 0.52), either in 8 studies on incidence of emergence delirium (RR = 0.43; 95% CI, 0.13–1.37, p = 0.15). The pooled analysis using a fixed-effect model showed that remimazolam was associated with a statistically significant increase in the risk of PONV compared to non-Remimazolam groups (RR = 1.20, 95% CI: 1.02–1.42; p = 0.03). Other secondary outcomes, respiratory depression after extubation (RR = 0.96; 95% CI, 0.63–1.44, p = 0.84), extubation time (MD = -1.30, 95% CI: −3.46-0.85, p = 0.24) and length of hospital stay (MD = 0.08, 95% CI: −0.28-0.44, p = 0.65) showed no significant difference between remimazolam group and non-remimazolam group.ConclusionIn this systematic review and meta-analysis, prolonged continuous intravenous administration of remimazolam throughout the surgical procedure does not increase the risk of delirium compared to other anesthetic regimens. In addition, remimazolam has potential benefits in the pediatric population as it reduces the risk of ED.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251138775, Identifier: CRD420251138775.