Determination of effective dose of remimazolam benzenesulfonate to suppress cardiovascular responses to laryngeal mask placement in elderly patients_West China Medical Journal

Authors：

LIU Jia ¹ , ZHANG Erfei ² , WANG Li ¹ , XING Dong ¹ ,  NIE Huang ¹

1. Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi 710000, P. R. China;
2. Department of Anesthesiology, Affiliated Hospital of Yan’an University, Yan’an, Shaanxi 716000, P. R. China;

Corresponding author：

NIE Huang, Email: niehuang@163.com

Keywords：

Elderly patients; remimazolam; laryngeal mask anesthesia; cardiovascular response; dose-effect relationship

DOI：

10.7507/1002-0179.202311252

Video：

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Objective To investigate the effective dose of remimazolam benzenesulfonate to suppress cardiovascular responses to laryngeal mask placement in elderly patients. Methods Elderly patients undergoing laryngeal mask anesthesia between March and June 2023 were selected. Combined with sulfentanil 0.2 μg/kg, remimazolam was used as induction hypnotic. The first patient was given remizolam benzenesulfonate 0.16 mg/kg infused by pump for 1 min. The dose of remimazolam for the next patient was determined by the biased coin up-and-down method based on the patient’s response to the laryngeal mask placement. The score of Modified Observer’s Assessment of Alert/Sedation, vital signs and anesthesia depth index (AI) were recorded during induction. Probit analysis was used to calculate the half effective dose (ED₅₀), 95% effective dose (ED₉₅) and half effective AI (AI₅₀). According to the statistical requirements, at least 45 negative patients were required. Results A total of 53 elderly patients were enrolled in the study until the end of the trial. The ED₅₀ and ED₉₅ of remimazolam benzenesulfonate for inhibiting cardiovascular responses to laryngeal mask insertion were 0.154 mg/kg [95% confidence interval (CI) (0.034, 0.170) mg/kg] and 0.207 mg/kg [95%CI (0.190, 0.614) mg/kg], respectively. AI decreased during induction, with an AI₅₀ of 64.119 [95%CI (60.609, 69.984)]. Conclusion When combined with 0.2 μg/kg sufentanil, infusing 0.2 mg/kg remimazolam benzenesulfonate for 1 min is effective and safe for laryngeal mask anesthesia induction in elderly patients.

Citation： LIU Jia, ZHANG Erfei, WANG Li, XING Dong, NIE Huang. Determination of effective dose of remimazolam benzenesulfonate to suppress cardiovascular responses to laryngeal mask placement in elderly patients. West China Medical Journal, 2024, 39(2): 240-244. doi: 10.7507/1002-0179.202311252 Copy

1.	Vann MA. The future of ambulatory surgery for geriatric patients. Best Pract Res Clin Anaesthesiol, 2023, 37(3): 343-355.
2.	Lu Z, Zheng H, Chen Z, et al. Effect of etomidate vs propofol for total intravenous anesthesia on major postoperative complications in older patients: a randomized clinical trial. JAMA Surg, 2022, 157(10): 888-895.
3.	Hannam JA, Mitchell SJ, Cumin D, et al. Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery. Br J Anaesth, 2019, 122(2): 198-205.
4.	Yang JJ, Lei L, Qiu D, et al. Effect of remimazolam on postoperative delirium in older adult patients undergoing orthopedic surgery: a prospective randomized controlled clinical trial. Drug Des Devel Ther, 2023, 17: 143-153.
5.	Lu K, Wei S, Ling W, et al. Remimazolam versus propofol for deep sedation/anaesthesia in upper gastrointestinal endoscopy in elderly patients: a multicenter, randomized controlled trial. J Clin Pharm Ther, 2022, 47(12): 2230-2236.
6.	Tran DQ, Dugani S, Correa JA, et al. Minimum effective volume of lidocaine for ultrasound-guided supraclavicular block. Reg Anesth Pain Med, 2011, 36(5): 466-469.
7.	袁静, 丁素娟, 夏江燕, 等. 丙泊酚靶控输注时羟考酮抑制气管插管反应的半数有效剂量. 临床麻醉学杂志, 2017, 33(11): 1050-1052.
8.	俞冰, 赵耐青, 林燧恒. 二阶段随机抽样数据阈值模型的统计分析方法比较. 复旦学报(医学版), 2008, 35(1): 75-79.
9.	李姣阳, 杨玉峰, 宫春利, 等. 麻醉深度指数和 Narcotrend 指数的临床应用比较. 国际麻醉学与复苏杂志, 2020, 41(12): 1151-1154.
10.	付阳, 许涛, 谢克亮, 等. 麻醉深度指数和脑电双频指数在静脉麻醉中判断意识变化的多中心比较研究. 国际麻醉学与复苏杂志, 2018, 39(11): 1005-1009.
11.	Borkett KM, Riff DS, Schwartz HI, et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg, 2015, 120(4): 771-780.
12.	Chae D, Kim HC, Song Y, et al. Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study. Br J Anaesth, 2022, 129(1): 49-57.
13.	Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics, 2002, 58(1): 171-177.
14.	Gold MI, Sacks DJ, Grosnoff DB, et al. Comparison of propofol with thiopental and isoflurane for induction and maintenance of general anesthesia. J Clin Anesth, 1989, 1(4): 272-276.
15.	George RB, McKeen D, Columb MO, et al. Up-down determination of the 90% effective dose of phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients undergoing cesarean delivery. Anesth Analg, 2010, 110(1): 154-158.
16.	Wang J, Huang J, Yang S, et al. Pharmacokinetics and safety of esketamine in Chinese patients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study. Drug Des Devel Ther, 2019, 13: 4135-4144.
17.	Liu M, Sun Y, Zhou L, et al. The median effective dose and bispectral index of remimazolam tosilate for anesthesia induction in elderly patients: an up-and-down sequential allocation trial. Clin Interv Aging, 2022, 17: 837-843.
18.	Olutoye OA, Yu X, Govindan K, et al. The effect of obesity on the ED₉₅ of propofol for loss of consciousness in children and adolescents. Anesth Analg, 2012, 115(1): 147-153.
19.	秦菲菲, 廉仲明, 黄亚茹, 等. 复合阿芬太尼时瑞马唑仑抑制双腔支气管插管反应的半数有效剂量. 临床麻醉学杂志, 2023, 39(4): 375-378.
20.	钱淑雯, 郭旋, 沈耘, 等. 复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的半数有效剂量. 临床麻醉学杂志, 2024, 40(1): 61-64.
21.	Xiao Y, Cao Y, Pu J, et al. The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial. BMC Anesthesiol, 2024, 24(1): 48.
22.	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.
23.	Polanczyk CA, Marcantonio E, Goldman L, et al. Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery. Ann Intern Med, 2001, 134(8): 637-643.
24.	Zeng Y, Feng Q, Hesketh T, et al. Survival, disabilities in activities of daily living, and physical and cognitive functioning among the oldest-old in China: a cohort study. Lancet, 2017, 389(10079): 1619-1629.
25.	Christensen K, Thinggaard M, Oksuzyan A, et al. Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart. Lancet, 2013, 382(9903): 1507-1513.
26.	Nolen SC, Evans MA, Fischer A, et al. Cancer-incidence, prevalence and mortality in the oldest-old. A comprehensive review. Mech Ageing Dev, 2017, 164: 113-126.

1. Vann MA. The future of ambulatory surgery for geriatric patients. Best Pract Res Clin Anaesthesiol, 2023, 37(3): 343-355.
2. Lu Z, Zheng H, Chen Z, et al. Effect of etomidate vs propofol for total intravenous anesthesia on major postoperative complications in older patients: a randomized clinical trial. JAMA Surg, 2022, 157(10): 888-895.
3. Hannam JA, Mitchell SJ, Cumin D, et al. Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery. Br J Anaesth, 2019, 122(2): 198-205.
4. Yang JJ, Lei L, Qiu D, et al. Effect of remimazolam on postoperative delirium in older adult patients undergoing orthopedic surgery: a prospective randomized controlled clinical trial. Drug Des Devel Ther, 2023, 17: 143-153.
5. Lu K, Wei S, Ling W, et al. Remimazolam versus propofol for deep sedation/anaesthesia in upper gastrointestinal endoscopy in elderly patients: a multicenter, randomized controlled trial. J Clin Pharm Ther, 2022, 47(12): 2230-2236.
6. Tran DQ, Dugani S, Correa JA, et al. Minimum effective volume of lidocaine for ultrasound-guided supraclavicular block. Reg Anesth Pain Med, 2011, 36(5): 466-469.
7. 袁静, 丁素娟, 夏江燕, 等. 丙泊酚靶控输注时羟考酮抑制气管插管反应的半数有效剂量. 临床麻醉学杂志, 2017, 33(11): 1050-1052.
8. 俞冰, 赵耐青, 林燧恒. 二阶段随机抽样数据阈值模型的统计分析方法比较. 复旦学报(医学版), 2008, 35(1): 75-79.
9. 李姣阳, 杨玉峰, 宫春利, 等. 麻醉深度指数和 Narcotrend 指数的临床应用比较. 国际麻醉学与复苏杂志, 2020, 41(12): 1151-1154.
10. 付阳, 许涛, 谢克亮, 等. 麻醉深度指数和脑电双频指数在静脉麻醉中判断意识变化的多中心比较研究. 国际麻醉学与复苏杂志, 2018, 39(11): 1005-1009.
11. Borkett KM, Riff DS, Schwartz HI, et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg, 2015, 120(4): 771-780.
12. Chae D, Kim HC, Song Y, et al. Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study. Br J Anaesth, 2022, 129(1): 49-57.
13. Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics, 2002, 58(1): 171-177.
14. Gold MI, Sacks DJ, Grosnoff DB, et al. Comparison of propofol with thiopental and isoflurane for induction and maintenance of general anesthesia. J Clin Anesth, 1989, 1(4): 272-276.
15. George RB, McKeen D, Columb MO, et al. Up-down determination of the 90% effective dose of phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients undergoing cesarean delivery. Anesth Analg, 2010, 110(1): 154-158.
16. Wang J, Huang J, Yang S, et al. Pharmacokinetics and safety of esketamine in Chinese patients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study. Drug Des Devel Ther, 2019, 13: 4135-4144.
17. Liu M, Sun Y, Zhou L, et al. The median effective dose and bispectral index of remimazolam tosilate for anesthesia induction in elderly patients: an up-and-down sequential allocation trial. Clin Interv Aging, 2022, 17: 837-843.
18. Olutoye OA, Yu X, Govindan K, et al. The effect of obesity on the ED₉₅ of propofol for loss of consciousness in children and adolescents. Anesth Analg, 2012, 115(1): 147-153.
19. 秦菲菲, 廉仲明, 黄亚茹, 等. 复合阿芬太尼时瑞马唑仑抑制双腔支气管插管反应的半数有效剂量. 临床麻醉学杂志, 2023, 39(4): 375-378.
20. 钱淑雯, 郭旋, 沈耘, 等. 复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的半数有效剂量. 临床麻醉学杂志, 2024, 40(1): 61-64.
21. Xiao Y, Cao Y, Pu J, et al. The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial. BMC Anesthesiol, 2024, 24(1): 48.
22. 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.
23. Polanczyk CA, Marcantonio E, Goldman L, et al. Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery. Ann Intern Med, 2001, 134(8): 637-643.
24. Zeng Y, Feng Q, Hesketh T, et al. Survival, disabilities in activities of daily living, and physical and cognitive functioning among the oldest-old in China: a cohort study. Lancet, 2017, 389(10079): 1619-1629.
25. Christensen K, Thinggaard M, Oksuzyan A, et al. Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart. Lancet, 2013, 382(9903): 1507-1513.
26. Nolen SC, Evans MA, Fischer A, et al. Cancer-incidence, prevalence and mortality in the oldest-old. A comprehensive review. Mech Ageing Dev, 2017, 164: 113-126.

West China Medical Journal

Determination of effective dose of remimazolam benzenesulfonate to suppress cardiovascular responses to laryngeal mask placement in elderly patients

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