BR Biomedical Reports 2049-9434 2049-9442 D.A. Spandidos BR-22-1-01891 10.3892/br.2024.1891 Articles Efficacy and safety of remimazolam vs. propofol for general anesthesia with tracheal intubation: Systematic review and meta‑analysis LuoHong 1 TangZuolei 2 Department of Anesthesiology, 363 Hospital, Wuhou, Chengdu, Sichuan 610041, P.R. China Department of Anesthesiology, Tianfu New District People's Hospital, Shuangliu, Chengdu, Sichuan 610200, P.R. China Correspondence to: Professor Zuolei Tang, Department of Anesthesiology, Sichuan Tianfu New District People's Hospital, 97, Zhengbei Street, Shuangliu, Chengdu, Sichuan 610200, P.R. China 17307293@qq.com 01 2025 15 11 2024 22 1 13 22 04 2024 11 07 2024 Copyright: © 2024 Luo and Tang. 2024 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Remimazolam is an ultra-short-acting intravenous benzodiazepine derivative approved for sedation during gastroscopy and colonoscopy. The present study aimed to compare the safety and efficacy of remimazolam and propofol for general anesthesia with tracheal intubation by meta-analysis. A comprehensive search was conducted in databases, including PubMed, Embase, Cochrane Library and Web of Science, to identify relevant randomized controlled trials (RCTs). The search period was from the inception of these databases until February 2024. All eligible randomized controlled trials that report at least one outcome of interest were subjected to quality assessment and data extraction by two researchers independently using Review Manager 5.4 software. Data analysis was conducted using R software. A total of 14 RCTs with 1,275 patients were included for meta-analysis. Compared with propofol, remimazolam significantly reduced incidence of hypotension [odds ratio (OR)=0.31, 95% confidence interval (CI; 0.23, 0.43), P<0.0001], bradycardia [OR=0.06, 95% CI (0.00, 1.20), P=0.06] and injection pain [OR=0.02, 95% CI (0.01, 0.08), P<0.0001] with shorter time to recovery of consciousness (ROC) [mean difference (MD)=5.47 min, 95% CI (-10.70, -0.24 min), P=0.04] but longer time to loss of consciousness [MD=37.01 sec, 95% CI (24.42, 49.60 sec), P<0.0001]. Remimazolam was a safer and more effective alternative to propofol for general anesthesia with tracheal intubation and demonstrated a lower risk of adverse events with shorter time to ROC.

 general anesthesia meta-analysis propofol remimazolam tracheal intubation Funding: No funding was received. Introduction

General anesthesia with tracheal intubation is a key procedure in surgical settings that necessitate effective sedation and muscle relaxation (1). General anesthesia, which induces a reversible state of unconsciousness, analgesia and muscle relaxation, has a rich history dating back to the 19th century when ether and chloroform were first used. Since then, numerous advancements have been made, with propofol emerging as a widely used intravenous anesthetic agent for induction and maintenance of anesthesia (2,3). Despite its widespread use, propofol is associated with certain limitations, including injection pain and dose-dependent cardiorespiratory depression (4,5). Other commonly used sedatives, such as midazolam (6), etomidate (7) and dexmedetomidine (8), also demonstrate similar drawbacks.

Remimazolam is an ultra-short-acting intravenous benzodiazepine derivative and has been approved for sedation during gastroscopy and colonoscopy (9-11). It acts on γ-aminobutyric acid type A receptors and is rapidly metabolized by tissue esterase enzymes into an inactive form (12). Due to its rapid onset and offset of action, short recovery time, rare accumulation following long-term infusion and fewer serious side effects, remimazolam has been approved by regulatory authorities for general anesthesia as an alternative to other currently commonly used sedatives (first approved in January 2020 in Japan and the European Commission in April 2023) (13,14). Despite these promising attributes, to the best of our knowledge, there is a lack of comprehensive evidence comparing remimazolam directly with propofol for general anesthesia with tracheal intubation. The present meta-analysis aimed to pool data from eligible studies to provide a comprehensive evaluation of the comparative efficacy and safety profiles of remimazolam and propofol for general anesthesia with tracheal intubation.

 Materials and methods <sec> <title>Literature search

A comprehensive search was conducted in databases, including PubMed (ncbi.nlm.nih.gov/pubmed/), Embase (Embase.com), Cochrane Library (https://www.cochranelibrary.com/), and Web of Science (https://www.webofscience.com/wos/), to identify relevant studies. The search period was from the inception of these databases until February 2024. The search strategy employed specific keywords such as ‘remimazolam’, ‘propofol’, ‘general anesthesia’, ‘tracheal intubation’, ‘endotracheal intubation’ and ‘control’ (Table I).

 Inclusion criteria

Only randomized controlled trials (RCTs) were considered for inclusion, regardless of whether they implemented allocation concealment or blinding methods. The intervention group received remimazolam (group R) as an intravenous anesthetic, either alone or in combination with analgesics such as sufentanil and rocuronium, as well as muscle relaxants. The comparison group received propofol (group P) as intravenous anesthetic and the same combination of drugs as the remimazolam group. The selected literature needed to report ≥1 of the following outcome measures: Time to loss of consciousness (LOC), time to recovery of consciousness (ROC), time to extubation and occurrence of adverse reactions such as hypotension, injection pain, bradycardia, nausea or vomiting and hypoxemia.

 Exclusion criteria

Patients who did not undergo endotracheal intubation were excluded from the study. Additionally, studies without control groups, literature types such as reviews, case reports or abstracts, those without full-text availability, lacking relevant outcome measures or written in languages other than English were also excluded.

 Data extraction and quality assessment

Two independent investigators performed the literature screening based on the aforementioned inclusion and exclusion criteria. Once the eligible studies were identified, data extraction was conducted using a standardized form. The extracted information included the first author, publication year, age and sex distribution of the study population, sample size and details regarding the anesthesia induction and maintenance protocols in the experimental and control groups. Any discrepancies were resolved through discussion.

In accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Version 5), the Cochrane Risk of Bias Tool was employed to assess the methodological quality of the included studies (15). The risk of bias assessment encompassed random sequence generation, allocation concealment, blinding, intention-to-treat analysis, completeness of data, selecting outcome reporting and other potential biases associated with baseline comparability. The evaluation was performed independently by two researchers using Review Manager (Version 5.4; Cochrane Collaboration, 2020.

The present systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (16) and the protocol was registered in the PROSPERO database (ID no. CRD42024520840; crd.york.ac.uk/prospero/#myprospero).

 Statistical analysis

Data analysis was conducted using R software (4.1.2) (17). Categorical variables were assessed using odds ratio (OR) and their corresponding 95% confidence interval (CI), while continuous variables were analyzed using mean difference (MD) and their corresponding 95% CI. The included studies were considered heterogenous based on the guidance of Cochrane Handbook and a random effect model was used for the meta-analysis. Publication bias among the included studies was assessed using funnel plots and Egger's test (18). P<0.05 was considered to indicate a statistically significant difference.

 Results <sec> <title>Literature search

A comprehensive search yielded 638 relevant articles. After eliminating duplicates, 484 unique articles remained. Assessment of titles and abstracts led to the exclusion of 353 studies that were irrelevant to the research question. Following this initial screening, the full texts of the remaining 131 articles were obtained and subjected to evaluation based on the predetermined inclusion and exclusion criteria. Consequently, 117 studies were excluded from the final analysis due to reasons such as being review articles, not adhering to the specified study design or lacking the requisite outcome variables. Ultimately, 14 articles fulfilled the inclusion criteria and were included in the present study (Fig. 1).

 General characteristics of included studies

Included studies were published from 2021 to 2023. The sample sizes of the studies ranged between 40 and 190 participants, aggregating to a total of 1,275 individuals. Among the included articles, group R comprised 686 cases, while group P encompassed 598 cases. A comprehensive summary of included studies is shown in Table II.

 Quality assessment of included studies

All 14 included articles were RCTs (Fig. 2). However, there were instances of unclear and high risk of bias. One study had unclear randomization (19) and another used admission order for random allocation (20), posing a high risk of bias. Two studies had unclear allocation concealment (19,20), while five did not report blinding, resulting in an unclear risk (19-23). None of the studies mentioned intention-to-treat analysis and one study did not address baseline comparability (24), both of which were categorized as unclear risk. Overall, all included studies had some degree of bias, with uncertain impact on the reliability and stability of the combined results.

 Meta-analysis. Time to LOC

A total of five studies (20,21,25-27), involving a total of 396 patients, investigated the time to LOC. Significant heterogeneity was observed between the included studies (P<0.01; I2=96%). The random effects model revealed that group R had a significantly longer time to LOC compared with group P [MD=37.01 sec, 95% CI (24.42, 49.60 sec), P<0.0001]. This indicated that the intervention in group R led to delayed onset of unconsciousness (Fig. 3).

Time to ROC. A total of six studies (21-23,25-27), involving a total of 472 patients, examined the time to ROC. Significant heterogeneity was found between the included studies (P<0.01; I2=93%). The random effects model revealed that group R had a significantly shorter time to ROC compared with group P [MD=-5.47 min, 95% CI (-10.70, -0.24 min), P=0.04]. This indicated that the intervention in group R led to a faster ROC (Fig. 4).

Time to extubation. A total of five studies (22,23,25-27), comprising a total of 432 patients, examined the time to extubation. Significant heterogeneity was found between the included studies (P<0.01; I2=94%). The random effects model indicated no significant difference in time to extubation between groups [MD=-5.21 min, 95% CI (-10.90, 0.49 min), P=0.07]. This finding suggested that the intervention in group R did not have a significant impact on the duration of extubation (Fig. 5).

Hypotension. A total of 11 studies (19,20,22-24,27-32), comprising a total of 968 patients, investigated the incidence of hypotension. Although the studies showed relatively low heterogeneity (P=0.07; I2=42%), a random effects model was used and found a significant reduction in the incidence of hypotension in group R compared with group P [OR=0.32, 95% CI (0.21, 0.48), P<0.0001; Fig. 6].

Injection pain. A total of four studies (19,20,22,29), comprising a total of 410 patients, investigated the incidence of injection pain. Although the studies showed minimal heterogeneity (P=0.78; I2=0%), a random effects model was used in the meta-analysis and found a significant reduction in the incidence of injection pain in group R compared with group P [OR=0.02, 95% CI (0.01, 0.08), P<0.0001; Fig. 7].

Bradycardia. A total of four studies (27,28,30,32), involving a total of 321 patients, examined the incidence of bradycardia. Although the studies showed minimal heterogeneity (P=0.46; I2=0%), a random effects model was used in the meta-analysis. The incidence of bradycardia in group R was significantly lower compared with group P [OR=0.26, 95% CI (0.11, 0.58), P=0.001; Fig. 8].

Nausea or vomiting. A total of seven studies (19,20,23,25,26,29,32), including a total of 777 patients, investigated the incidence of nausea or vomiting. Although the studies demonstrated a low heterogeneity (P=0.29; I2=20%), a random effects model was used. No significant difference in the occurrence of nausea or vomiting was found between groups [OR=0.69, 95% CI (0.26, 1.85), P=0.46]. This suggested intervention in group R did not have a significant effect on the incidence of nausea or vomiting (Fig. 9).

Hypoxemia. A total of three studies (26,29,32), including a total of 394 patients, investigated the incidence of hypoxemia; hypoxemia was reported in one study. The random effects model was used and did not find any significant difference in occurrence of hypoxemia between groups [OR=0.06, 95% CI (0.00, 1.20), P=0.07]. This suggested that the intervention in group R did not have a statistically significant impact on the incidence of hypoxemia (Fig. 10).

 Publication bias

Hypotension was reported in 11 studies as the most frequently studied outcome (19,20,22-24,27-32). A funnel plot was used to assess publication bias for hypotension and showed an asymmetrical scatter distribution (Fig. 11). Utilizing Egger's test for quantitative analysis, the results yielded a non-significant P value of 0.19, indicating no significant publication bias in the studies.

 Discussion

The present meta-analysis assessed the efficacy and safety of remimazolam over propofol as an anesthetic agent in general anesthesia with tracheal intubation and supported the superiority of remimazolam. Compared with propofol, general anesthesia with tracheal intubation on remimazolam led to a reduction in time to ROC by 5.47 min and an increase in time to LOC by 37 sec. Although no significant difference was found in time to extubation, remimazolam still demonstrated a trend towards a shorter time to extubation. These outcomes suggested that remimazolam may facilitate a more favorable recovery profile, which is key in clinical settings where rapid patient recovery is essential.

Prior to the emergence of remimazolam, both intravenous and volatile anesthetic agents used in general anesthesia exerted cardiovascular depressant effects, which could result in severe low cardiac output and bradycardia in patients with impaired cardiac function. Here, remimazolam was associated with a significantly lower incidence of hypotension, bradycardia and injection pain. Specifically, the incidence of hypotension was reduced by 69% and bradycardia by 75% in patients administered remimazolam compared with those given propofol. Additionally, the incidence of injection pain was markedly lower in the remimazolam group, indicating an advantage for patients sensitive to injection discomfort.

The present findings align with previous studies that highlighted the stable hemodynamic properties of remimazolam (13,33). For example, Nakayama et al (34) emphasized the minimal cardiovascular depression associated with remimazolam, which is particularly beneficial for elderly and critically ill patients. Furthermore, its metabolism independent of organ function renders it suitable for patients with hepatic or renal impairment (12,33). It also decreases surgical stress response and respiratory depression without significant myocardial depression, resulting in fewer anesthesia-associated adverse reactions (23,31,35). However, in patients routinely taking long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, remimazolam has high incidence of hypotensive events (up to 62.5%, compared with 82.9% for propofol) during induction and maintenance of general anesthesia. Therefore, further evaluation of the potential adverse events of remimazolam in specific patient populations is still needed.

Rapid recovery time and superior safety profile of remimazolam could enhance patient throughput and decrease postoperative monitoring requirements, thereby improving surgical workflow and patient outcomes. Unlike propofol which does not have a specific antagonist and may lead to unpredictable delayed recovery following general anesthesia, the effects of remimazolam, as a benzodiazepine, can be completely reversed by flumazenil. The availability of flumazenil as a specific antagonist for remimazolam provides an added safety measure, although its routine use should be approached with caution due to potential re-sedation risks. This is because flumazenil only competitively antagonizes GABAA receptors, and as the plasma concentration of flumazenil decreases, the sedative effect of remimazolam may reappear (36,37). It is important to continue monitoring patients for a sufficient duration after administering flumazenil.

The present study has limitations that should be acknowledged. The visible differences in remimazolam and propofol make it challenging to conduct a double-blind clinical trial, which may introduce potential bias. Variability in surgical procedures and dosages between studies may also contribute to heterogeneity. While Egger's test did not indicate significant bias, this does not entirely rule out the possibility of bias affecting the results. The asymmetry in the funnel plot should be interpreted cautiously. Further sensitivity analyses on age, sex and dosage and stricter requirements on study quality can provide additional insights into the robustness of the conclusions drawn from the present meta-analysis. In addition, the studies included in the present meta-analysis were conducted in Asian countries. This may limit the generalizability of the findings to other populations.

In conclusion, remimazolam is a safer and more effective alternative to propofol for general anesthesia with tracheal intubation, with lower risk of adverse events such as hypotension, bradycardia and injection pain and a shorter time to ROC.

 Acknowledgements

The authors would like to thank Dr Mengru Zhang (Hull York Medical School, Shanghai, China) for assistance with protocol registration in the PROSPERO database and Mr Sam Morice (Castle Hill Hospital, Hull, United Kingdom) for language editing.

 Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

 Authors' contributions

HL and ZT conceived and designed the study, performed the literature review and analyzed and interpreted data. HL wrote the manuscript. HL and ZT confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

 Ethics approval and consent to participate

Not applicable.

 Patient consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

 References WojciechowskiPJ17-General Anesthesia. In: Stehr W, editor. The mont reid surgical handbook (sixth edition). Philadelphia: W.B. Saunders 181-191, 2008. ChauPLNew insights into the molecular mechanisms of general anaestheticsBr J Pharmacol16128830720102073541610.1111/j.1476-5381.2010.00891.x MahmoudMMasonKPRecent advances in intravenous anesthesia and anestheticsF1000Res7F100020182975573110.12688/f1000research.13357.1 Propofol. In: Aronson JK, editor. Meyler's side effects of drugs (sixteenth edition). Oxford: Elsevier; 988-1016, 2016. SahinovicMMStruysMMRFAbsalomARClinical pharmacokinetics and pharmacodynamics of propofolClin Pharmacokinet571539155820183001917210.1007/s40262-018-0672-3 ConwayAChangKMafeldSSutherlandJMidazolam for sedation before procedures in adults and children: A systematic review updateSyst Rev106920213367387810.1186/s13643-021-01617-5 KotaniYPiersantiGMaiucciGFresilliSTuriSMontanaroGZangrilloALeeTCLandoniGEtomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trialsJ Critical Care7715431720233712702010.1016/j.jcrc.2023.154317 KhareASharmaSPDeganwaMLSharmaMGillNEffects of dexmedetomidine on intraoperative hemodynamics and propofol requirement in patients undergoing laparoscopic cholecystectomyAnesth Essays Res111040104520172928487210.4103/aer.AER_107_17 RexDKBhandariRDestaTDeMiccoMPSchaefferCEtzkornKBarishCFPruittRCashBDQuirkDA phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopyGastrointest Endosc88427437.e620182972351210.1016/j.gie.2018.04.2351 PambiancoDJBorkettKMRiffDSWinklePJSchwartzHIMelsonTIWilhelm-OgunbiyiKA phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopyGastrointest Endosc8398499220162636333310.1016/j.gie.2015.08.062 BorkettKMRiffDSSchwartzHIWinklePJPambiancoDJLeesJPWilhelm-OgunbiyiKA phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopyAnesth Analg12077178020152550284110.1213/ANE.0000000000000548 GoudraBGSinghPM. Remimazolam: The future of its sedative potentialSaudi J Anaesth838839120142519119310.4103/1658-354X.136627 KilpatrickGJRemimazolam: Non-clinical and clinical profile of a new sedative/anesthetic agentFront Pharmacol1269087520213435458710.3389/fphar.2021.690875 HuQLiuXWenCLiDLeiXRemimazolam: An updated review of a new sedative and anaestheticDrug Des Devel Ther163957397420223641185910.2147/DDDT.S384155 DoiMMoritaKTakedaJSakamotoAYamakageMSuzukiTEfficacy and safety of remimazolam versus propofol for general anesthesia: A multicenter, single-blind, randomized, parallel-group, phase IIb/III trialJ Anesth3454355320203241797610.1007/s00540-020-02788-6 PageMJMcKenzieJEBossuytPMBoutronIHoffmannTCMulrowCDShamseerLTetzlaffJMAklEABrennanSEThe PRISMA 2020 statement: An updated guideline for reporting systematic reviewsBMJ372n7120213378205710.1136/bmj.n71 R Core Team. The R Project for Statistical Computing [updated 14/06/2024. Available from: https://www.r-project.org/. LinLChuHQuantifying publication bias in meta-analysisBiometrics7478579420182914109610.1111/biom.12817 LiJZhouDJinYZhouHSFangCLZhuZQXiongLLDifference between remimazolam toluenesulfonic acid and propofol in waking quality and conscious state after general anesthesiaIbrain717118020213778679810.1002/j.2769-2795.2021.tb00081.x XuQWuJShanWDuanGLanHEffects of remimazolam combined with sufentanil on hemodynamics during anesthetic induction in elderly patients with mild hypertension undergoing orthopedic surgery of the lower limbs: A randomized controlled trialBMC Anesthesiol2331120233771019610.1186/s12871-023-02249-z GaoJYangCJiQLiJEffect of remimazolam versus propofol for the induction of general anesthesia on cerebral blood flow and oxygen saturation in elderly patients undergoing carotid endarterectomyBMC Anesthesiol2315320233714297110.1186/s12871-023-02095-z QiuYGuWZhaoMZhangYWuJThe hemodynamic stability of remimazolam compared with propofol in patients undergoing endoscopic submucosal dissection: A randomized trialFront Med993894020223600437610.3389/fmed.2022.938940 TangFYiJMGongHYLuZYChenJFangBChenCLiuZYRemimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery patients under general anesthesiaWorld J Clin Cases9105951060320213500499110.12998/wjcc.v9.i34.10595 SongSWKimSParkJHChoYHJeonYGPost-induction hypotension with remimazolam versus propofol in patients routinely administered angiotensin axis blockades: A randomized control trialBMC Anesthesiol2321920233734969010.1186/s12871-023-02188-9 ChoiJYLeeHSKimJYHanDWYangJYKimMJSongYComparison of remimazolam-based and propofol-based total intravenous anesthesia on postoperative quality of recovery: A randomized non-inferiority trialJ Clin Anesth8211095520223602970410.1016/j.jclinane.2022.110955 ShiFChenYLiHZhangYZhaoTEfficacy and safety of remimazolam tosilate versus propofol for general anesthesia in cirrhotic patients undergoing endoscopic variceal ligationInt J Gen Med1558359120223504671610.2147/IJGM.S345390 SoKYParkJKimSHSafety and efficacy of remimazolam for general anesthesia in elderly patients undergoing laparoscopic cholecystectomy: A randomized controlled trialFront Med (Lausanne)10126586020233802011210.3389/fmed.2023.1265860 ChoiEKJangYParkSJComparison of remimazolam and propofol induction on hemodynamic response in hypertensive patientsMedicine (Baltimore)102e3435820233750515310.1097/MD.0000000000034358 DaiGPeiLDuanFLiaoMZhangYZhuMZhaoZZhangXSafety and efficacy of remimazolam compared with propofol in induction of general anesthesiaMinerva Anestesiol871073107920213426358110.23736/S0375-9393.21.15517-8 KuangQZhongNYeCZhuXWeiFPropofol versus remimazolam on cognitive function, hemodynamics, and oxygenation during one-lung ventilation in older patients undergoing pulmonary lobectomy: A randomized controlled trialJ Cardiothorac Vasc Anesth371996200520233742233610.1053/j.jvca.2023.06.027 LiuTLaiTChenJLuYHeFChenYXieYEffect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trialPharmacol Res Perspect9e0085120213439022810.1002/prp2.851 MaoYGuoJYuanJZhaoEYangJQuality of recovery after general anesthesia with remimazolam in patients' undergoing urologic surgery: A randomized controlled trial comparing remimazolam with propofolDrug Des Devel Ther16119920920223550949010.2147/DDDT.S359496 KimKMRemimazolam: Pharmacological characteristics and clinical applications in anesthesiologyAnesth Pain Med1711120223513960810.17085/apm.21115 NakayamaJOgiharaTYajimaRInnamiYOuchiTAnesthetic management of super-elderly patients with remimazolam: A report of two casesJA Clin Rep77120213452814510.1186/s40981-021-00474-4 SatohTNishiharaNSawashitaYOhnoSHirataNYamakageMRemimazolam anesthesia for mitraclip implantation in a patient with advanced heart failureCase Rep Anesthesiol2021553644220213403596510.1155/2021/5536442 HohjohHHorikawaINakagawaKSegi-NishidaEHasegawaHInduced mRNA expression of matrix metalloproteinases Mmp-3, Mmp-12, and Mmp-13 in the infarct cerebral cortex of photothrombosis model miceNeurosci Lett73913540620203298713110.1016/j.neulet.2020.135406 WuQXuFWangJJiangMComparison of remimazolam-flumazenil versus propofol for recovery from general anesthesia: A systematic review and meta-analysisJ Clin Med12731620203806836810.3390/jcm12237316

Flowchart of literature selection.

Cochrane bias risk assessment of included studies. (A) Summary of bias risk. (B) Bias risk of each study.

Meta-analysis of time to loss of consciousness. R, remimazolam; P, propofol.

Meta-analysis of time to recovery of consciousness. R, remimazolam; P, propofol.

Meta-analysis of time to extubation. R, remimazolam; P, propofol.

Meta-analysis of hypotension. R, remimazolam; P, propofol.

Meta-analysis of injection pain. R, remimazolam; P, propofol.

Meta-analysis of bradycardia. R, remimazolam; P, propofol.

Meta-analysis of nausea or vomiting. R, remimazolam; P, propofol.

Meta-analysis of hypoxemia. R, remimazolam; P, propofol.

Funnel plot of hypotension.

Literature search strategy.

A, PubMed
Search number Query
#1 Search ‘tracheal intubation’ [Mesh]
#2 Search ((tracheal intubation [Title/Abstract]) OR endotracheal intubation [Title/Abstract])
#3 #1 OR #2
#4 Search (((remimazolam [Title/Abstract]) AND propofol [Title/Abstract]) AND control [Title/Abstract])
#5 Search ((anesthesia [Title/Abstract]) OR general anesthesia [Title/Abstract])
#6 #3 AND #4 AND #5
B, Cochrane
# 1 MeSH descriptor: (tracheal intubation) explode all trees
# 2 ((tracheal intubation*) OR (endotracheal intubation*)): ti, ab, kw
# 3 #1 OR #2
# 4 MeSH descriptor: (remimazolam) explode all trees
# 5 MeSH descriptor: (propofol) explode all trees
# 6 MeSH descriptor: (control) explode all trees
# 7 MeSH descriptor: (anesthesia) explode all trees
# 8 ((anesthesia*) OR (general anesthesia*)): ti, ab, kw
# 9 #7 OR #8
#10 #3 AND #4 AND #5 AND #6 AND #9
C, Embase
#1 ‘tracheal intubation’/exp OR ‘endotracheal intubation’: ti, ab
#2 ‘remimazolam’: ti, ab AND ‘propofol’: ti,ab AND ‘control’: ti, ab
#3 ‘anesthesia’: ti, ab OR ‘general anesthesia’: ti,ab
#4 #1 AND #2 AND #3
D, Web of science
#1 TS=(tracheal intubation OR endotracheal intubation)
#2 TI=(remimazolam AND propofol AND control AND anesthesia)
#3 #1 AND #2

General characteristics of studies.

  Sample size Age, years Sex, M/F   Induction dosage Maintenance dosage  
First author, year Country R P R P R P Surgery R P R P (Refs.)
Li et al, 2021 China 52 52 48.6±13.8a 46.8±11.3a 24/28 25/27 Elective endotracheal intubation 0.2 mg/kg 2.5 mg/kg 0.2-0.6 mg/kg/h 4.0-10.0 mg/kg/h (19)
Xu et al, 2023 China 30 30 69.9±4.3a 68.6±3.3a 14/16 13/17 Orthopedic 0.2 mg kg 1.5 mg/kg Remifentanil 10.0-15.0 µg/kg/h/1.02.0% sevoflurane Remifentanil 10.0-15.0 µg/kg/h & 1.0%-2.0% sevoflurane (20)
Gao et al, 2023 China 20 20 67.22±4.4a 67.2±4.4a 16/4 15/5 Carotid artery stenosis 0.3 mg/kg 1.5-2.0 mg/kg Sevoflurane at adjusted concentration Sevoflurane at adjusted concentration (21)
Qiu et al, 2022 China 28 28 62.8±7.1a 64.7±8.9a 21/7 19/9 Endoscopic submucosal dissection 0.3 mg/kg 2.0 mg/kg NR NR (22)
Tang et al, 2021 China 40 40 54.9±8.5a 52.7±7.0a 25/15 20/20 Cardiac 0.3 mg/kg 1.5 mg/kg NR NR (23)
Song et al, 2023 South Korea 40 41 58.6±6.4a 60.1±5.2a 25/15 28/13 NR 6.0 mg/kg/h 2.0 mg/kg 1.0 mg/kg/h 1.0 mg/kg/h (24)
Choi et al, 2022 South Korea 70 69 39.5 (33.0-48.0)b 41.0 (37.0-47.0)b 0/70 0/69 Open thyroidectomy 6.0 mg/kg/h 5.0 µg/ml 1.0-2.0 mg/kg/h 2.0-6.0 µg/ml (25)
Shi et al, 2022 China 38 38 52.7±4.9a 51.6±5.55a 16/22 18/20 Endoscopic variceal ligation 0.2 mg/kg 2.0 mg/kg 1.0-2.0 mg/kg/h NR (26)
So et al, 2023 South Korea 42 39 74.5 (70.0-78.3)b 76.0 (70.0-81.0)b 22/20 20/19 Elective laparoscopic cholecystectomy 6.0 mg/kg/h 1.5-2.0 mg/kg 1.0-2.0 mg/kg/h 100.0 µg/kg/min (27)
Choi et al, 2023 South Korea 48 48 52.3±9.1a 52.8±8.2a 26/22 22/26 NR 6.0 mg/kg/h 1.5-2.0 mg/kg 1.0 mg/kg/h 3.0-6.0 mg/kg/h (28)
Dai et al, 2021 China 142 48 47.9±13.6a 52.0±13.7a 86/56 26/22 Elective 0.2-0.4 mg/kg 2.0 mg/kg Sufentanil/remifentanil 6.0-8.0 mg/kg Sufentanil/remifentanil 6.0-8.0 mg/kg (29)
Kuang et al, 2023 China 42 42 65.4±3.9a 65.2±4.4a 19/23 20/22 Lobectomy 0.3 mg/kg 2.0 mg/kg 0.6-1.2 mg/kg/h 2.0-10.0 mg/kg/h (30)
Liu et al, 2021 China 30 30 54.9±11.3a 50.6±10.5a 14/16 17/13 Valve replacement 1.8 mg/kg/h 2.5 µg/ml Sufentanil 0.2 µg/kg/h/dexmedetomidine 0.5 µg/kg/h Sufentanil 0.2 µg/kg/h/dexmedetomidine 0.5 µg/kg/h (31)
Mao et al, 2022 China 64 64 52.5±17.5a 50.0±25.8a 41/23 45/19 Urological 0.2-0.3 mg/kg 2.0-3.0 mg/kg 1.0-2.0 mg/kg/h 4.0-10.0 mg/kg/h (32)

Data are presented as

amean and SD or

bmedian and range. R, remimazolam; P, propofol; M, male; F, female; NR, not reported.