The Median Effective Dose and Bispectral Index of Remimazolam Tosilate for Anesthesia Induction in Elderly Patients: An Up-and-Down Sequential Allocation Trial

Abstract

Purpose Remimazolam is a new type of ultrashort benzodiazepine drug with an unclear optimal dose for general anesthesia induction in elderly patients aged >60 years. Therefore, this study aimed to determine the effective dose of remimazolam tosilate induction and explore its correlation with the bispectral index (BIS). Patients and Methods A total of 42 elderly patients were divided into two age groups: 60–69 (group A) and 70–85 (group B) years. An initial dose of 0.1mg/kg(Group A) and 0.05 mg/kg(Group B) remimazolam tosilate was administered, and the Modified Observer’s Assessment of Alertness/Sedation scale was used to assess adequate responses. The dose was calculated using the up-and-down allocation technique based on the previous response. The sequential formula and probit regression model were used to calculate ED50 and BIS50. ED95 was determined using the probit regression model. Results The ED50 of remimazolam tosilate for anesthesia induction were 0.088 mg/kg (95% confidence interval [CI] 0.071–0.108) and 0.061 mg/kg (95% CI 0.053–0.069) in groups A and B, respectively. ED95 was 0.118 mg/kg (95% CI 0.103–0.649) and 0.090 mg/kg (95% CI 0.075–0.199) in groups A and B, respectively. The remimazolam tosilate administration could decrease BIS. BIS50 was 86.0 (95% CI 83.7–88.6) and 85.4 (95% CI 84.1–86.8) in groups A and B, respectively. Conclusion During the induction process, patients’ consciousness should be observed. The dose of remimazolam tosilate could be chosen after careful consideration of individual variations.

Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial

“…19,21,22 RT, a new ultra-short-acting type of GABA A receptor agonist, has been widely used in procedural sedation and general anesthesia due to its promising properties, including a rapid onset, short recovery time and stable hemodynamics. 23,24 Our results showed that the hemodynamic fluctuation (∆MAP) in group LR and group E were significantly lower than that in group HR, while the ∆HR between the three groups were noted no significant difference. Although the average difference of ∆MAP between the three groups are only a few mmHg (19.67 vs 18.45 vs 24.85 mmHg, respectively), these minor hemodynamic changes may affect the balance between myocardial oxygen supply and demand, especially for patients with potential myocardial ischemia risk.…”

Clinical profile of a new anesthetic: remimazolam

“…Remimazolam has been approved for use as an anesthetic and sedative for adults; however, the scope of approval varies from country to country, e.g., it is used as a general anesthetic in Japan and South Korea and a procedural sedative also in South Korea, the USA, China, and European countries [1]. After market approval, remimazolam has been used as sedative in various procedures, such as gastrointestinal endoscopy, colonoscopy, and bronchoscopy [4,5], and as anesthetic in various surgeries, such as urologic surgery, robotic gastrectomy, and cardiac surgery [6][7][8][9][10][11][12][13][14].…”

“…In a situation where a syringe pump may not be used, bolus dosing of remimazolam may be adopted; however, it is not currently recommended because stable injection may not be ensured [17]. Recently, several studies on bolus dosing of remimazolam for inducing anesthesia and sedation have been conducted (Table 1) [4,10,21,22]. Dai et al [4] suggested that complete anesthesia induction without rescue sedation can be achieved with 0.4 mg/kg of remimazolam; however, 0.3 mg/kg of remimazolam is more appropriate considering the dose-dependent risk of remimazolam-induced hypotension.…”

“…In general, although dose adjustment is not necessary for the elderly, previous studies demonstrated that the ED95 of remimazolam decreases as age increases [10,21]. Increasing age was significantly associated with lower ED95 for anesthesia induction, i.e., 0.12 mg/kg (95% CI 0.103-0.649) and 0.09 mg/kg (95% CI 0.075-0.199) for patients aged 60-69 and 70-85 years, respectively [10]. Chae et al [21] also proposed that the optimal doses were 0.25-0.33, 0.19-0.25, and 0.14-0.19 mg/kg for patients aged <40, 60-80, and more than 80 years, respectively.…”

Remimazolam: another option for induction of general anesthesia?

“…Second, commercially available infusion pumps and pharmacokinetic models for the target-controlled infusion of remimazolam are limited. Third, anesthesia depth monitoring indices, such as the bispectral index (Medtronic, Ireland) or patient state index (Masimo, USA), are not well correlated with loss of consciousness in general anesthesia with remimazolam [ 10 , 11 ]. Fourth, interactions with other drugs used for general anesthesia, particularly opioid analgesics, have not been studied sufficiently.…”