Remimazolam-based total intravenous vs. sevoflurane-based balanced general anesthesia on perioperative outcomes in adult surgical patients: a systematic review and meta-analysis

Background: Remimazolam is a novel intravenous anesthetic increasingly used as an alternative to traditional inhalational agents like sevoflurane. This systematic review and meta-analysis compared perioperative outcomes of remimazolam versus sevoflurane in adult patients undergoing general anesthesia. Methods: We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science through May 2025 for randomized controlled trials (RCTs) and observational studies comparing the two agents. Primary outcomes included intraoperative mean arterial pressure (MAP), heart rate (HR), incidence of hypotension, use of vasopressors, postoperative delirium (POD), postoperative nausea and vomiting (PONV), and antiemetic use. Secondary outcomes included recovery efficiency metrics. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were pooled using a random-effects model. Results: Fourteen studies with 1,593 patients (nine RCTs, five observational studies) were included. Remimazolam maintained higher MAP intraoperatively (e.g., 30 min after incision: MD = 7.91 mmHg; 95% CI [4.99, 10.83]; P < 0.0001; I² = 43.8%) and higher HR (e.g., 1 h after incision: MD = 6.23 bpm; 95% CI [3.21, 9.25]; P < 0.0001; I² = 0%) except in the PACU. Vasopressor use was lower with remimazolam (RR = 0.38; 95% CI [0.15, 0.99]; P = 0.0485; I² = 89.7%), while IOH incidence was similar. Remimazolam significantly reduced PONV (RR = 0.61; 95% CI [0.42, 0.89]; P = 0.0101; I² = 18.6%) without increasing POD (RR = 1.08; 95% CI [0.73, 1.59]; P = 0.7048; I² = 0%). Eye-opening time was shorter (MD = − 121.87 s; 95% CI [–164.20, − 79.55]; P < 0.0001; I² = 0%), while anesthesia, operation, and extubation times were comparable. RCT-only analyses confirmed most findings with reduced heterogeneity. Conclusion: Remimazolam-based anesthesia was associated with modestly more stable hemodynamics and reduced PONV without clear differences in recovery or POD. Larger, well-designed multicenter randomized trials are needed to confirm these findings in broader populations. Registration: Our protocol has been registered with PROSPERO under the following registration number: CRD42024523733.