Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial
Abstract
Purpose This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. Methods Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0-2.5 mg/kg until LoC followed by 4-10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. Results Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (- 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p Conclusions This trial demonstrated that remimazolam was well tolerated and non-inferior to propofol with regard to efficacy as a sedative hypnotics for general anesthesia. Clinical trial registration This trial is registered with the Japan Pharmaceutical Information Center - Clinical Trials Information (JapicCTI). JapicCTI number: 121973.
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There was no statistically significant difference in prevalence of nausea and vomiting between remimazolam and propofol (OR = 1.32; 95% CI, 0.73 to 2.39; I2 = 33%).
“Based on the fixed-effects model, the OR of remimazolam to propofol in the subgroup of nausea and vomiting was 1.32 95% CI, 0.73 to 2.39; I² = 33%) (Fig. 12), indicating that there existed no statistical conspicuous discrepancy in the prevalence of nausea and vomiting between the 2 arms.”
There was no difference in prevalence of bradycardia between remimazolam and propofol groups.
“There was no difference when the prevalence of bradycardia between the 2 groups was compared (17,19).”
Risk of bias was high in 2 trials and moderate in 2 trials for blinding of patients and personnel.
“The risk of bias was rated as high in 2 trials and moderate in 2 trials for the domain of patients and personnel blinding (15-18).”
No meaningful change in nausea/vomiting results was obtained with sensitivity analysis and random-effects model.
“No meaningful change in the results was obtained when the sensitivity analysis and the random-effects model were used (15,17,18,20,22).”
Only one study was assessed as high-risk for publication bias because it did not report pooled HR values.
“Only one study was assessed as high-risk in the domain of publication bias because it did not report its pooled HR values (17).”
Cites
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Remimazolam: non-clinical and clinical profile of a new sedative/anesthetic agent
Kilpatrick, G. J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.690875 · Cited by 262 · see citing works
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“However, a study evaluating the efficacy and safety of remimazolam versus propofol for general anesthesia showed a longer time to extubation in remimazolam group than propofol group.(9) Liu also found remimazolam may worsen elderly patients’ postoperative cognitive functions in upper gastrointestinal endoscopy.”
BackgroundResultBarbosa, E. C., Espírito Santo, P. A., Baraldo, S., & Meine, G. C. (2024) · British Journal of Anaesthesia · doi:10.1016/j.bja.2024.02.005 · Cited by 111 · see citing works
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Application effects of remimazolam and propofol on elderly patients undergoing hip replacement
Zhang, J., Wang, X., Zhang, Q., Wang, Z., & Zhu, S. (2022) · BMC Anesthesiology · doi:10.1186/s12871-022-01641-5 · Cited by 86 · see citing works
Efficacy and safety of remimazolam in endoscopic sedation-A systematic review and meta-analysis
Zhu, X., Wang, H., Yuan, S., Li, Y., Jia, Y., Zhang, Z., Yan, F., & Wang, Z. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655042 · Cited by 75 · see citing works
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Induction and maintenance of procedural sedation in adults: focus on remimazolam injection
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- Authors
- Doi, M., Morita, K., Takeda, J., Sakamoto, A., Yamakage, M., & Suzuki, T.
- Affiliations
- Hamamatsu University Hospital (JP)
- Okayama University (JP)
- Keio University (JP)
- Nippon Medical School (JP)
- Sapporo Medical University (JP)
- Tokai University (JP)
- Corresponding author
- Doi, Matsuyuki
- Venue
- Journal of Anesthesia
- Published
- 2020-05-16
- Volume
- 34
- Issue
- 4
- Pages
- 543-553
- ISSN
- 0913-8668 (ISSN-L)
- 1438-8359
- OpenAlex
- W3024474933
- Cited by
- 484
- References
- 1
- Citations by year
- 2026: 53 · 2025: 94 · 2024: 115 · 2023: 100 · 2022: 78 · 2021: 39 · 2020: 5
- FWCI
- 64.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Anesthesia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Keywords
- remimazolam, propofol, general anesthesia, non-inferiority, intravenous sedation, anesthesia induction, anesthesia maintenance, loss of consciousness, extubation time, adverse drug reactions, blood pressure reduction, injection site pain, surgical patients
- MeSH terms
- Anesthesia, General, Benzodiazepines, Double-Blind Method, Humans, Hypnotics and Sedatives, Japan, Midazolam, Propofol, Single-Blind Method, Anesthetics, Intravenous
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