Alfentanil Enhanced the Sedation of Remimazolam During Anaesthesia Induction in Patients Undergoing Urological Day Surgery: A Randomised Controlled Trial

Abstract

Background: Remimazolam is a novel benzodiazepine sedative agent. Combining opioids with sedatives exerts a synergistic effect. The aim is to investigate whether alfentanil enhances sedative effects of remimazolam during anaesthesia induction in patients undergoing urological day surgery.

Methods: This was a single-centre, single-blinded, randomised clinical trial. The study was conducted between 1 September 2022 and 31 December 2023. We included 114 patients undergoing urological day surgery under general anaesthesia. Patients were randomly assigned to the RMZ-AF or AF-RMZ group (n=57). During induction, the RMZ-AF group received remimazolam then alfentanil, and the AF-RMZ group received alfentanil then remimazolam. Primary outcome was the time from remimazolam administration to loss of consciousness (LOC) during induction. Secondary outcomes included anaesthetic and surgical characteristics, vital signs, and adverse events.

Results: The time from remimazolam administration to LOC was shorter in the AF-RMZ group compared with the RMZ-AF group (87.3 [25.7] s vs 132.3 [32.3] s, P<0.0001). Similarly, the time from remimazolam administration to a bispectral index (BIS) ≤ 60 was shorter in the AF-RMZ group compared with the RMZ-AF group (168.2 [58.1] s vs 207.8 [61.6] s, P=0.0006). Although no significant difference in the total amount of remimazolam administration between groups was observed, the RMZ-AF group required a higher dose of remimazolam to achieve LOC (P<0.0001) and to reach a BIS of ≤ 60 (P=0.0058). No significant differences were observed between groups in the total administration of alfentanil, ephedrine, rocuronium, or crystalloid infusion volumes. The most common adverse events were hypotension, hypertension, and tachycardia, with no significant difference between groups.

Conclusion: Alfentanil enhanced remimazolam's sedative effects during anaesthesia induction in patients undergoing urological day surgery. The combination of remimazolam and alfentanil for general anaesthesia would improve efficacy, reducing the adverse effects and dosage of drug. But the potential mechanisms need further study.

Clinical trial registration: The trial was registered before patient enrolment at http://www.chictr.org.cn (ChiCTR2200064130, principal investigator: Xuehai Guan; date of registration: 27 September 2022, https://www.chictr.org.cn/showproj.html?proj=179023).

Keywords: alfentanil; anaesthesia; day surgery; remimazolam; sedation.

Figure 1

CONSORT diagram for the trial. CONSORT indicates Consolidated Standards for Reporting of Trials.

Figure 2

Changes in vital signs of patients receiving remimazolam combined with or without alfentanil for anaesthesia induction. Data are displayed as means (SD) (A–C) or medians (D). Data were compared using repeated-measures two-way analysis of variance (ANOVA) with Geisser-Greenhouse correction, followed by Bonferroni`s multiple comparisons test. (A) Drug: F (1, 112) = 0.8040, p=0.3718; Time: F (11, 1232) = 127.5, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 1.597, p=0.0936; Subject: F (112.1232) = 8.416, p<0.0001. (B) Drug: F (1, 112) = 0.0362, p=0.8494; Time: F (11, 1232) = 11.92, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 7.392, p<0.0001; Subject: F (112.1232) = 14.33, p<0.0001. (C) Drug: F (1, 112) = 1.045, p=0.3088; Time: F (11, 1232) = 11.43, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 0.5367, p=0.8793; Subject: F (112.1232) = 4.385, p<0.0001. (D) Drug: F (1, 112) = 0.7292, p=0.3950; Time: F (8, 896) = 639.0, p<0.0001; Drug Ⅹ Time: F (8, 896) = 1.627, p=0.1131; Subject: F (112.896) = 3.800, p<0.0001.