Abstract Background Remimazolam is a novel ultra-short-acting benzodiazepine sedative, but its clinical positioning, delirium risk profile, and comparative efficacy against standard-of-care sedatives remain incompletely defined. This study aimed to comprehensively evaluate its efficacy and safety compared with propofol (Analysis A) and dexmedetomidine (Analysis B) across diverse clinical settings. Methods Two independent meta-analyses were performed: Analysis A compared remimazolam vs. propofol in intubated surgical adults (primary endpoint: postoperative delirium incidence and recovery quality); Analysis B compared remimazolam vs. dexmedetomidine in perioperative/ICU adults with sedation (primary endpoint: time to achieve target sedation). Standard meta-analytic methods, trial sequential analysis (TSA), meta-regression, GRADE evidence grading, and heterogeneity source analysis were applied. Results Analysis A (vs. Propofol): Remimazolam showed a delirium risk comparable to propofol (OR 1.06, 95% CI 0.78–1.45; Moderate certainty), a finding confirmed by TSA as robust. Quality of recovery (QoR-15) was similar between two agents (MD -1.85, 95% CI -7.01 to 3.31), though the certainty was very low due to very serious inconsistency and serious imprecision (I 2 = 91.2%). Remimazolam significantly reduced the incidence of intraoperative hypotension. Analysis B (vs. Dexmedetomidine): Remimazolam significantly hastened sedation onset (MD -4.78 min, 95%CI: -8.8 to -0.88). Regarding recovery, TSA confirmed firm evidence that remimazolam offers no clinically meaningful advantage (≥ 5 min) in time to full alertness. Incidences of PONV were comparable across all groups. Conclusions Remimazolam is a safe and effective alternative to propofol for surgical anesthesia, offering superior hemodynamic stability without increasing the risk of postoperative delirium. Compared with dexmedetomidine, remimazolam provides a faster onset of sedation, an advantage that may be especially pronounced in patients with pre-existing agitation. It is well-suited for ambulatory, high-turnover surgery and hemodynamically vulnerable populations. Its long-term neurocognitive safety in ICU sedation requires further investigation.
Li et al. (Thu,) studied this question.