Remimazolam compared with propofol,
dexmedetomidine, and midazolam for adult sedation in
flexible bronchoscopy: a systematic review and meta-
analysis

Luiz Fábio Silva Ribeiro; Lucas Rezende de Freitas; Tauãna Terra Cordeiro de Oliveira; Laiz Gomes Carneiro Novaes; Rafael Arsky Lombardi

doi:10.1016/j.bjane.2026.844729

Review Article

Remimazolam compared with propofol, dexmedetomidine, and midazolam for adult sedation in flexible bronchoscopy: a systematic review and meta- analysis

Remimazolam comparado com propofol, dexmedetomidina e midazolam para sedação em adultos em broncoscopia flexível: revisão sistemática e meta-análise

Luiz Fábio Silva Ribeiro, Lucas Rezende de Freitas, Tauãna Terra Cordeiro de Oliveira, Laiz Gomes Carneiro Novaes, Rafael Arsky Lombardi

http://dx.doi.org/10.1016/j.bjane.2026.844729 Braz J Anesthesiol, vol.76, n3, 844729, 2026

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Abstract

Background

Remimazolam, a short-acting benzodiazepine, has emerged as a potential safer alternative for sedation in Flexible Bronchoscopy (FB). This meta-analysis compares its efficacy and safety with Propofol, Dexmedetomidine, and Midazolam in adult patients undergoing FB.

Methods

PubMed, Embase, and Cochrane databases were searched on July 17, 2025, for trials comparing Remimazolam with other sedatives. Primary outcomes included hypotension, bradycardia, and intraprocedural opioid consumption; secondary outcomes were hypoxia, respiratory depression, patient satisfaction, induction time, and recovery time. Pooled Risk Ratios (RR), Mean Differences (MD), and Standardized Mean Differences (SMD) were calculated using a random-effects model in R (4.4.0). Risk of bias was assessed using the RoB2 tool, and subgroup analyses were conducted for each comparator.

Results

Eleven trials (1,884 patients) were included. Remimazolam reduced respiratory depression (RR = 0.44 [95% CI 0.29; 0.67]; p = 0.0002; I² = 0%), hypoxia incidence (RR = 0.60 [95% CI 0.39; 0.93]; p = 0.0227; I² = 64.7%), bradycardia (RR = 0.39 [95% CI 0.20; 0.77]; p = 0.0069; I² = 52.3%), and hypotension (RR = 0.61 [95% CI 0.40; 0.95]; p = 0.0289; I² = 74.0%) compared to all sedatives. Compared to Propofol, Remimazolam reduced the incidence of hypotension (RR = 0.42 [95% CI 0.31; 0.58]; p < 0.0001; I² = 0%), respiratory depression (RR = 0.41 [95% CI 0.25; 0.68]; p = 0.0005; I² = 12.3%), but increased induction time (MD = 0.61 min [95% CI 0.23; 0.99]; p = 0.002; I² = 90.9%). Compared to Dexmedetomidine, it improved satisfaction (SMD = 0.23 [95% CI 0.07; 0.39]; p = 0.004; I² = 0%) and reduced recovery time (MD = -1.79 min [95% CI -2.66; -0.92]; p < 0.001; I² = 90.7%), hypoxia incidence (RR = 0.49 [95% CI 0.28; 0.88]; p = 0.0162; I² = 60.3%), and induction time (MD = -2.21 min [95% CI -2.41; -2.00]; p < 0.001; I² = 0%). Compared to Midazolam, Remimazolam increased sedation success (RR = 2.03 [95% CI 1.40; 2.95]; p = 0.0002; I² = 50%), shortened induction time (MD = -0.69 min [95% CI -1.37; -0.01]; p = 0.047; I² = 81.5%), and recovery time (MD = -4.49 min [95% CI -7.06; -1.92]; p < 0.001; I² = 40.9%).

Conclusions

Remimazolam reduced respiratory depression overall and demonstrated improved safety, faster recovery, and greater efficacy compared to Propofol, Dexmedetomidine, and Midazolam, respectively, supporting its potential as an effective alternative for sedation in FB. Nonetheless, substantial heterogeneity in certain outcomes and the relatively small sample size in some comparisons limit the generalizability of our findings.

Systematic review protocol

PROSPERO (CRD 42024568148).

Keywords

Dexmedetomidine; Flexible bronchoscopy; Midazolam; Propofol; Remimazolam; Sedation

Resumo

Introdução

O remimazolam, uma benzodiazepina de ação curta, surgiu como uma potencial alternativa mais segura para sedação em broncoscopia flexível (Flexible Bronchoscopy — FB). Esta meta-análise compara sua eficácia e segurança com propofol, dexmedetomidina e midazolam em pacientes adultos submetidos à FB.

Métodos

Foram pesquisadas as bases PubMed, Embase e Cochrane em 17 de julho de 2025 para ensaios clínicos comparando remimazolam com outros sedativos. Os desfechos primários incluíram hipotensão, bradicardia e consumo intraprocedimento de opioides; os desfechos secundários foram hipoxemia, depressão respiratória, satisfação do paciente, tempo de indução e tempo de recuperação. Foram calculados Risk Ratios (RR), diferenças de médias (MD) e diferenças de médias padronizadas (SMD) utilizando modelo de efeitos aleatórios no R (4.4.0). O risco de viés foi avaliado pelo instrumento RoB2, e análises de subgrupos foram realizadas para cada comparador.

Resultados

Onze ensaios (1.884 pacientes) foram incluídos. O remimazolam reduziu depressão respiratória (RR = 0,44 [IC 95% 0,29–0,67]; p = 0,0002; I² = 0%), incidência de hipoxemia (RR = 0,60 [IC 95% 0,39–0,93]; p = 0,0227; I² = 64,7%), bradicardia (RR = 0,39 [IC 95% 0,20–0,77]; p = 0,0069; I² = 52,3%) e hipotensão (RR = 0,61 [IC 95% 0,40–0,95]; p = 0,0289; I² = 74,0%) em comparação com todos os sedativos. Em relação ao propofol, reduziu a incidência de hipotensão (RR = 0,42 [IC 95% 0,31–0,58]; p < 0,0001; I² = 0%) e depressão respiratória (RR = 0,41 [IC 95% 0,25–0,68]; p = 0,0005; I² = 12,3%), porém aumentou o tempo de indução (MD = 0,61 min [IC 95% 0,23–0,99]; p = 0,002; I² = 90,9%). Em comparação com dexmedetomidina, melhorou a satisfação (SMD = 0,23 [IC 95% 0,07–0,39]; p = 0,004; I² = 0%) e reduziu o tempo de recuperação (MD = -1,79 min [IC 95% -2,66 a -0,92]; p < 0,001; I² = 90,7%), hipoxemia (RR = 0,49 [IC 95% 0,28–0,88]; p = 0,0162; I² = 60,3%) e tempo de indução (MD = -2,21 min [IC 95% -2,41 a -2,00]; p < 0,001; I² = 0%). Em comparação com midazolam, o remimazolam aumentou o sucesso da sedação (RR = 2,03 [IC 95% 1,40–2,95]; p = 0,0002; I² = 50%), reduziu o tempo de indução (MD = -0,69 min [IC 95% -1,37 a -0,01]; p = 0,047; I² = 81,5%) e o tempo de recuperação (MD = -4,49 min [IC 95% -7,06 a -1,92]; p < 0,001; I² = 40,9%).

Conclusão

O remimazolam reduziu a depressão respiratória de forma global e demonstrou melhor perfil de segurança, recuperação mais rápida e maior eficácia em comparação com propofol, dexmedetomidina e midazolam, respectivamente, sustentando seu potencial como alternativa eficaz para sedação em broncoscopia flexível. No entanto, a heterogeneidade substancial em alguns desfechos e o tamanho amostral relativamente pequeno em algumas comparações limitam a generalização dos achados.

Protocolo de revisão sistemática

PROSPERO (CRD 42024568148).

Palavras-chave

Dexmedetomidina; Broncoscopia flexível; Midazolam; Propofol; Remimazolam; Sedação

References

1. Miller RJ, Casal RF, Lazarus DR, Ost DE, Eapen GA. Flexible Bron- choscopy. Vol. 39, Clinics in Chest Medicine. W.B. Saunders; 2018. p. 1−16.

2. Lo YL, Lin TY, Fang YF, et al. Feasibility of Bispectral Index- Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial. PLoS One. 2011;6:e27769.

3. Lee H, Choe YH, Park S. Analgosedation during flexible fiberop- tic bronchoscopy: comparing the clinical effectiveness and safety of remifentanil versus midazolam/propofol. BMC Pulm Med. 2019;19:240.

4. Mehta AC, Prakash UBS, Garland R, et al. American College of Chest Physicians and American Association for Bronchology Con- sensus Statement. Chest. 2005;128:1742−55.

5. Vu VG, Hoang AD, Phan TP, et al. BM-BronchoLC - A rich bron- choscopy dataset for anatomical landmarks and lung cancer lesion recognition. Sci Data. 2024;11:321.

6. Guo Q, An Q, Zhao L, Wu M, Wang Y, Guo Z. Safety and Efficacy of Dexmedetomidine for Bronchoscopy: A Systematic Review and Meta-Analysis. J Clin Med. 2023;12:1607.

7. Lee M, Lee C, Choi GJ, Kang H. Remimazolam for Procedural Sedation in Older Patients: A Systematic Review and Meta- Analysis with Trial Sequential Analysis. J Pers Med. 2024;14:276.

8. Kim KM. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. Anesth Pain Med (Seoul). 2022;17:1−11.

9. Sahinovic MM, Struys MMRF, Absalom AR. Clinical Pharmacoki- netics and Pharmacodynamics of Propofol. Clin Pharmacokinet. 2018;57:1539−58.

10. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharma- codynamics of Dexmedetomidine. Clin Pharmacokinet. 2017;56:893−913.

11. Lingamchetty TN, Hosseini SA, Saadabadi A. Midazolam. 2023 Jun 5. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan−. PMID: 30726006.

12. Noor N, Legendre R, Cloutet A, Chitneni A, Varrassi G, Kaye AD. A comprehensive review of remimazolam for sedation. Health Psychol Res. 2021;9:24514.

13. Seol HY, Hong KS, Jang JG, et al. A prospective, open-label, ran- domized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design. BMC Pulm Med. 2024;24:243.

14. Jhuang BJ, Yeh BH, Huang YT, Lai PC. Efficacy and Safety of Remimazolam for Procedural Sedation: A Meta-Analysis of Ran- domized Controlled Trials with Trial Sequential Analysis. Front Med (Lausanne). 2021;8:641866.

15. McCambridge AJ, Boesch RP, Mullon JJ. Sedation in Bronchos- copy. Clin Chest Med. 2018;39:65−77.

16. Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2023.

17. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int J Surg. 2010;8:336−41.

18. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan ‒ a web and mobile app for systematic reviews. Syst Rev. 2016;5:210.

19. Brown P, Brunnhuber K, Chalkidou K, et al. How to formulate research recommendations. BMJ. 2006;333:804−6.

20. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:ED000142.

21. Higgins JPT, Altman DG, Gotzsche PC, et al. The Cochrane Col- laboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343. d5928-d5928.

22. Baujat B, Mahé C, Pignon J, Hill C. A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Stat Med. 2002;21:2641−52.

23. Wu Q, Xu R, Zhou X, et al. Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double- blind, controlled trial. Medicine (United States). 2024;103: E37215.

24. Zhou YY, Yang ST, Duan KM, et al. Efficacy and safety of remima- zolam besylate in bronchoscopy for adults: A multicenter, ran- domized, double-blind, positive-controlled clinical study. Front Pharmacol. 2022;13:1005367.

25. Chen X, Xin D, Xu G, Zhao J, Lv Q. The Efficacy and Safety of Remimazolam Tosilate Versus Dexmedetomidine in Outpatients Undergoing Flexible Bronchoscopy: A Prospective, Randomized, Blind, Non-Inferiority Trial. Front Pharmacol. 2022;13:902065.

26. Xu H, Wang L, Zhu W, Ren C, Liu G, Liu Y. Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmede- tomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial. Drug Des Devel Ther. 2024;18:2317−27.

27. Kane SP. Opioid (Opiate) Equianalgesia Conversion Calculator. ClinCalc. 2017. https://clincalc.com/Opioids Updated March 12, Accessed July 29, 2025.

28. Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid- quartile range. Stat Methods Med Res. 2018;27:1785−805.

29. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

30. Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557−60.

31. Zhang L, Yu L, Xu L, Wang JF, Li JY, Chen ZJ. Effectiveness of remimazolam besylate combined with alfentanil for fiberoptic bronchoscopy with preserved spontaneous breathing: a pro- spective, randomized, controlled clinical trial. Eur Rev Med Pharmacol Sci. 2023;27:6071−80.

32. Pastis NJ, Yarmus LB, Schippers F, et al. Safety and Efficacy of Remimazolam Compared with Placebo and Midazolam for Moderate Sedation During Bronchoscopy. Chest. 2019;155:137−46.

33. Kim SH, Cho JY, Kim M, et al. Safety and efficacy of remimazo- lam compared with midazolam during bronchoscopy: a single- center, randomized controlled study. Sci Rep. 2023;13:20498.

34. Gao S, Wang T, Cao L, Li L, Yang S. Clinical effects of remimazo- lam alone or in combination with dexmedetomidine in patients receiving bronchoscopy and influences on postoperative cogni- tive function: a randomized-controlled trial. Int J Clin Pharm. 2023;45:137−45.

35. Chai B, Guo J, Xu Z, et al. Comparison of the efficacy and safety of remimazolam and propofol for fiberoptic bronchoscopy in older patients: a prospective, randomized controlled study. BMC Geriatr. 2025;25:337.

36. Luo P, Wu J, Lan H, Xu Q, Duan G. Safety of remimazolam in deep sedation during flexible fiberoptic bronchoscopy: a pro- spective, randomized controlled trial. BMC Anesthesiol. 2025;25:246.

37. Zhou L, Zou J, Li X, Zuo X, Gu M, Sun K, et al. Efficacy and safety of remimazolam versus dexmedetomidine for patients undergo- ing flexible fiberoptic bronchoscopy: A randomized, clinical trial. J Clin Anesth. 2024;99:111677.

38. Kim KM. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. Anesth Pain Med (Seoul). 2022;17:1−11.

39. Tsuji Y, Koshika K, Ichinohe T. Effect of remimazolam and propo- fol anesthesia on autonomic nerve activities during Le Fort I osteotomy under general anesthesia: blinded randomized clini- cal trial. J Dent Anesth Pain Med. 2024;24:273−83.

40. Su H, Koomen JV, Eleveld DJ, Struys MMRF, Colin PJ. Pharmaco- dynamic mechanism-based interaction model for the haemody- namic effects of remifentanil and propofol in healthy volunteers. Br J Anaesth. 2023;131:222−33.

41. Bernasconi M, Chhajed PN, Müller P, Borer H. Patients’ satisfac- tion with flexible bronchoscopy in a hospital-based community practice. Respiration. 2009;78:440−5.

42. Andersen CØ, Travis H, Dehlholm-Lambertsen E, Russell R, Jørgensen EP. The Cost of Flexible Bronchoscopes: A Systematic Review and Meta-analysis. Pharmacoecon Open. 2022;6:787−97.

43. Zhang T, Li Q, Dong B, et al. Genetic Polymorphism of Drug Met- abolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Eth- nic Minorities in Heilongjiang Province, Northeast China. Pharmgenomics Pers Med. 2021;14:1537−47.

44. Ono C, Kikkawa H, Suzuki A, et al. Clinical impact of genetic variants of drug transporters in different ethnic groups within and across regions. Pharmacogenomics. 2013;14:1745−64.

45. Merali Z, Ross S, Paré G. The pharmacogenetics of carboxyles- terases: CES1 and CES2 genetic variants and their clinical effect. Drug Metabol Drug Interact. 2014;29:143−51.

Submitted date:
05/25/2025

Accepted date:
12/16/2025