Effectiveness and safety of remimazolam tosilate versus propofol for sedation in patients undergoing gastrointestinal endoscopy: a randomized controlled trial.

Publisher: Springer Country of Publication: Netherlands NLM ID: 101554912 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2210-7711 (Electronic) NLM ISO Abbreviation: Int J Clin Pharm Subsets: MEDLINE

Original Publication: Dordrecht : Springer

Propofol*/administration & dosage ; Propofol*/adverse effects ; Endoscopy, Gastrointestinal*/methods ; Alfentanil*/administration & dosage ; Alfentanil*/adverse effects ; Hypnotics and Sedatives*/adverse effects ; Hypnotics and Sedatives*/administration & dosage ; Benzodiazepines*/adverse effects ; Benzodiazepines*/administration & dosage ; Benzodiazepines*/therapeutic use; Humans ; Male ; Female ; Middle Aged ; Adult ; Patient Satisfaction ; Aged

Background: Remimazolam tosilate is a new type of benzodiazepine currently used for gastrointestinal endoscopy and can be combined with alfentanil.
Aim: This trial compared the effectiveness and safety of remimazolam with alfentanil to propofol with alfentanil in patients undergoing gastrointestinal endoscopy.
Method: One hundred and sixty-six patients were randomly divided into propofol-alfentanil anaesthesia (Group P) and remimazolam-alfentanil anaesthesia (Group R). The primary outcomes were perioperative haemodynamic variables, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO 2 ) preoperatively (T0); after anaesthesia induction (T1); when the gastroscope passed through the oropharynx (T2); 3 min (T3), 5 min (T4) and 7 min (T5) after T2; at the end of surgery (T6); and when patients successfully awakened (T7). The secondary outcomes included induction and awakening time, patient satisfaction, operator satisfaction, and adverse event occurrences.
Results: Compared with those in Group P, the SBP in Group R was significantly higher at T1, T2, T3, and T6 (P < 0.05); the DBP and MAP were significantly higher at T1, T2, T3, T5, and T6 (P < 0.05); the HR was significantly faster at T1 to T6 (P < 0.05); the SpO 2 was significantly higher at T1 to T4 (P < 0.05); the incidences of hypoxemia, hypotension, and drug injection pain were significantly lower in Group R (P < 0.05); the incidence of hiccups was higher (P < 0.05); the awakening time was shorter in Group R (P < 0.05); and the operator satisfaction score was high (P < 0.05).
Conclusion: Compared to propofol with alfentanil, remimazolam with alfentanil can be used safely and effectively for sedation in patients undergoing gastrointestinal endoscopy, with less impact on the patient's circulatory and respiratory systems and a lower incidence of adverse events.
Trial Registration: This trial protocol was registered in the Chinese Clinical Trial Registry (ChiCR2300077252, date: 2023-11-02).
Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hu B, Jiang K, Shi W, et al. Effect of remimazolam tosilate on respiratory depression in elderly patients undergoing gastroscopy: a multicentered, prospective, and randomized study. Drug Des Dev Ther. 2022;16:4151–9. https://doi.org/10.2147/DDDT.S391147 . (PMID: 10.2147/DDDT.S391147)
Shen XC, Ao X, Cao Y, et al. Etomidate-remifentanil is more suitable for monitored anesthesia care during gastroscopy in older patients than propofol-remifentanil. Med Sci Monit. 2015;21:1–8. https://doi.org/10.12659/MSM.891183 . (PMID: 255535064288392)
Zhou S, Zhu Z, Dai W, et al. National survey on sedation for gastrointestinal endoscopy in 2758 Chinese hospitals. Br J Anaesth. 2021;127(1):56–64. https://doi.org/10.1016/j.bja.2021.01.028 . (PMID: 10.1016/j.bja.2021.01.02833685636)
Zhu Q, Luo Z, Wang X, et al. Efficacy and safety of ciprofol versus propofol for the induction of anesthesia in adult patients: a multicenter phase 2a clinical trial. Int J Clin Pharm. 2023;45(2):473–82. https://doi.org/10.1007/s11096-022-01529-x . (PMID: 10.1007/s11096-022-01529-x3668062010147789)
Kang S, Hu L, Zhang B, et al. Efficacy, safety, and postoperative fatigue syndrome in combined alfentanil and propofol for patients with simple snoring undergoing gastroscopy with conscious or deep sedation levels. Asian J Surg. 2023;46(12):5605–6. https://doi.org/10.1016/j.asjsur.2023.08.013 . (PMID: 10.1016/j.asjsur.2023.08.01337597980)
Nakatsuka M, MacLeod AD. Hemodynamic and respiratory effects of transtracheal high-frequency jet ventilation during difficult intubation. J Clin Anesth. 1992;4(4):321–4. https://doi.org/10.1016/0952-8180(92)90138-q . (PMID: 10.1016/0952-8180(92)90138-Q1419013)
Chen J, Zou X, Hu B, et al. Remimazolam vs etomidate: haemodynamic effects in hypertensive elderly patients undergoing non-cardiac surgery. Drug Des Devel Ther. 2023;17:2943–53. https://doi.org/10.2147/DDDT.S425590 . (PMID: 10.2147/DDDT.S4255903778996810544010)
Zhao TY, Chen D, Sun H, et al. Moderate sedation with single-dose remimazolam tosilate in elderly male patients undergoing transurethral resection of the prostate with spinal anesthesia: a prospective, single-arm, single-centre clinical trial. BMC Anesthesiol. 2022;22(1):247. https://doi.org/10.1186/s12871-022-01788-1 . (PMID: 10.1186/s12871-022-01788-1359276189351252)
Vellinga R, Koomen JV, Eleveld DJ, et al. Target-controlled infusion of Remimazolam in healthy volunteers shows some acute tolerance. Anesthesiology. 2024;140(2):207–19. https://doi.org/10.1097/ALN.0000000000004811 . (PMID: 10.1097/ALN.000000000000481137889844)
Hu Q, Liu X, Wen C, et al. Remimazolam: an updated review of a new sedative and anaesthetic. Drug Des Dev Ther. 2022;16:3957–74. https://doi.org/10.2147/DDDT.S384155 . (PMID: 10.2147/DDDT.S384155)
Pastis NJ, Hill NT, Yarmus LB, et al. Correlation of vital signs and depth of sedation by modified observer’s assessment of alertness and sedation (MOAA/S) scale in bronchoscopy. J Bronchol Interv Pulmonol. 2022;29(1):54–61. https://doi.org/10.1097/LBR.0000000000000784 . (PMID: 10.1097/LBR.0000000000000784)
Saugel B, Sessler DI. Perioperative blood pressure management. Anesthesiology. 2021;134(2):250–61. https://doi.org/10.1097/ALN.0000000000003610 . (PMID: 10.1097/ALN.000000000000361033206118)
Xu Q, Wu J, Shan W, et al. Effects 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 trial. BMC Anesthesiol. 2023;23(1):311. https://doi.org/10.1186/s12871-023-02249-z . (PMID: 10.1186/s12871-023-02249-z3771019610500846)
Gao S, Wang T, Cao L, et al. Clinical effects of remimazolam alone or in combination with dexmedetomidine in patients receiving bronchoscopy and influences on postoperative cognitive function: a randomized-controlled trial. Int J Clin Pharm. 2023;45(1):137–45. https://doi.org/10.1007/s11096-022-01487-4 . (PMID: 10.1007/s11096-022-01487-436346544)
Lyu S, Deng Q, Lin W, et al. Randomized controlled trial for anesthesia during gastroscopy: interactions between remimazolam and propofol in combination with sufentanil. Int J Clin Pharm. 2023;45(4):857–63. https://doi.org/10.1007/s11096-023-01568-y . (PMID: 10.1007/s11096-023-01568-y3705565910366255)
Freyer N, Knöspel F, Damm G, et al. Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system. Drug Des Dev Ther. 2019;13:1033–47. https://doi.org/10.2147/DDDT.S186759 . (PMID: 10.2147/DDDT.S186759)
Wang C, Gao Y, Li J, et al. Safety and effectiveness of the combination of remimazolam tosilate and propofol in gastroscopy: a multicenter, randomized controlled, single-blind clinical trial. Front Pharmacol. 2023;14:1124667. https://doi.org/10.3389/fphar.2023.1124667 . (PMID: 10.3389/fphar.2023.11246673732449310264591)
Sahinovic MM, Struys M, Absalom AR. Clinical pharmacokinetics and pharmacodynamics of propofol. Clin Pharmacokinet. 2018;57(12):1539–58. https://doi.org/10.1007/s40262-018-0672-3 . (PMID: 10.1007/s40262-018-0672-3300191726267518)
Zhu H, Su Z, Zhou H, et al. Remimazolam dosing for gastroscopy: a randomized noninferiority trial. Anesthesiology. 2024;140(3):409–16. https://doi.org/10.1097/ALN.0000000000004851 . (PMID: 10.1097/ALN.000000000000485138039392)
Hasegawa G, Hirata N, Yoshikawa Y, et al. Differential effects of remimazolam and propofol on heart rate variability during anesthesia induction. J Anesth. 2022;36(2):239–45. https://doi.org/10.1007/s00540-022-03037-8 . (PMID: 10.1007/s00540-022-03037-835028756)
Gao YQ, Ihmsen H, Hu ZY, et al. Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children. Br J Anaesth. 2023;131(5):914–20. https://doi.org/10.1016/j.bja.2023.08.019 . (PMID: 10.1016/j.bja.2023.08.01937739904)
Luo W, Sun M, Wan J, et al. Efficacy and safety of remimazolam tosilate versus propofol in patients undergoing day surgery: a prospective randomized controlled trial. BMC Anesthesiol. 2023;23(1):182. https://doi.org/10.1186/s12871-023-02092-2 . (PMID: 10.1186/s12871-023-02092-23723733110214677)
Wang L, Wang Y, Ma L, et al. Cardiopulmonary adverse events of remimazolam versus propofol during cervical conization: a randomized controlled trial. Drug Des Dev Ther. 2023;17:1233–43. https://doi.org/10.2147/DDDT.S405057 . (PMID: 10.2147/DDDT.S405057)
Zhang L, Yu L, Xu L, et al. Effectiveness of remimazolam besylate combined with alfentanil for fiberoptic bronchoscopy with preserved spontaneous breathing: a prospective, randomized, controlled clinical trial. Eur Rev Med Pharmacol Sci. 2023;27(13):6071–80. https://doi.org/10.26355/eurrev_202307_32961 . (PMID: 37458656)
Guo J, Qian Y, Zhang X, et al. Remimazolam tosilate compared with propofol for gastrointestinal endoscopy in elderly patients: a prospective, randomized and controlled study. BMC Anesthesiol. 2022;22(1):180. https://doi.org/10.1186/s12871-022-01713-6 . (PMID: 10.1186/s12871-022-01713-6356892089185932)
Wei A, Ma S, Dou Y, et al. The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: a multicenter, randomized clinical trial. PLoS ONE. 2023;18(8):e0282930. https://doi.org/10.1371/journal.pone.0282930 . (PMID: 10.1371/journal.pone.02829303753561810399878)
Kilpatrick GJ. Remimazolam: non-clinical and clinical profile of a new sedative/anesthetic agent. Front Pharmacol. 2021;12:690875. https://doi.org/10.3389/fphar.2021.690875 . (PMID: 10.3389/fphar.2021.690875343545878329483)
Zhang Y, Dai G, Xu H, et al. Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia: a reply. Minerva Anestesiol. 2022;88(3):194–5. https://doi.org/10.23736/S0375-9393.21.16169-3 . (PMID: 10.23736/S0375-9393.21.16169-335315628)
Huang Q, Zou Y, Kong G. Hiccup, a neglected side-effect of remimazolam bolus? Minerva Anestesiol. 2022;88(3):193–4. https://doi.org/10.23736/S0375-9393.21.16086-9 . (PMID: 10.23736/S0375-9393.21.16086-934527413)
Ye E, Wu K, Ye H, et al. Comparison of 95% effective dose of remimazolam besylate and propofol for gastroscopy sedation on older patients: a single-centre randomized controlled trial. Br J Clin Pharmacol. 2023;89(11):3401–10. https://doi.org/10.1111/bcp.15839 . (PMID: 10.1111/bcp.1583937387195)
Chen S, Wang J, Xu X, et al. The efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy: a multicentered, randomized, positive-controlled, phase III clinical trial. Am J Transl Res. 2020;12(8):4594–603. (PMID: 329135337476156)
Yoshikawa Y, Maeda M, Kunigo T, et al. Effect of using hypotension prediction index versus conventional goal-directed haemodynamic management to reduce intraoperative hypotension in non-cardiac surgery: a randomised controlled trial. J Clin Anesth. 2024;93:111348. https://doi.org/10.1016/j.jclinane.2023.111348 . (PMID: 10.1016/j.jclinane.2023.11134838039629)
Futier E, Lefrant JY, Guinot PG, et al. Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery: a Randomized Clinical Trial. JAMA. 2017;318(14):1346–57. https://doi.org/10.1001/jama.2017.14172 . (PMID: 10.1001/jama.2017.14172289732205710560)

lzuyxcx-2022-108 Lanzhou University Medical Education Innovation and Development Program

Keywords: Alfentanil; Gastrointestinal endoscopy; Hypotension; Propofol; Remimazolam

YI7VU623SF (Propofol)
7V4A8U16MB (remimazolam)
1N74HM2BS7 (Alfentanil)
0 (Hypnotics and Sedatives)
12794-10-4 (Benzodiazepines)

Date Created: 20240731 Date Completed: 20241119 Latest Revision: 20241119

20241120

10.1007/s11096-024-01774-2

39083220