Efficacy of remimazolam tosilate versus propofol for total intravenous anaesthesia in urological surgery

Abstract

BACKGROUND Remimazolam is a novel ultra-short-acting benzodiazepine sedative that acts on the gamma-aminobutyric acid type A receptor (GABAAR). OBJECTIVE To compare the efficacies of remimazolam (RMZ), and propofol (PROP) combined with remifentanil and cisatracurium for total intravenous anaesthesia (TIVA) in patients undergoing urological surgery. DESIGN A prospective, single-blind, randomised, noninferiority clinical trial. SETTING Single centre from 1 January 2022 to 30 March 2022. PATIENTS A total of 146 adult patients undergoing elective urological surgery. INTERVENTION Patients were randomly allocated in a 1 : 1 ratio to the PROP or RMZ groups. In the PROP group, anaesthesia was induced with propofol at 100 mg min−1 to reach a bispectral index score (BIS) of 40 to 60. After loss of consciousness (LOC), intravenous fentanyl 3 μg kg−1 was administered, followed by cisatracurium 0.3 mg kg−1. Patients were intubated 3 min after cisatracurium administration. Anaesthesia was maintained with the combination of propofol (plasma concentration: 2.5 to 4 μg ml−1) and remifentanil (plasma concentration: 2.5 to 4 ng ml−1). In the RMZ group, anaesthesia was induced with remimazolam tosilate starting at 10 mg kg−1 h−1 to reach a BIS of 40 to 60 and maintained between 0.2 and 2 mg kg−1 h−1. After LOC, fentanyl and cisatracurium were administered and intubation was performed as in the PROP group. Anaesthesia was maintained with a combination of remimazolam (0.2 to 2 mg kg−1 h−1) and remifentanil (plasma concentration: 2.5 to 4 ng ml−1). MAIN OUTCOME MEASURES The primary outcome was the TIVA success rate. The predefined noninferiority margin considered an absolute difference of 6% in the primary outcome between the groups. The secondary outcomes were vital signs, anaesthesia and surgery characteristics, and adverse events. RESULTS All patients completed the trial. The success rates of TIVA with remimazolam and propofol were 100 and 98.6%, respectively. The incidence of hypotension during anaesthesia was lower in the RMZ group (26%) than in the PROP group (46.6%) (P = 0.016). The median [IQR] total consumption of ephedrine during anaesthesia was higher in the PROP group 10 [0 to 12.5] mg than in the RMZ group 0 [0 to 10] mg (P = 0.0002). The incidence of injection pain was significantly higher in the PROP group (76.7%) than in the RMZ group (0; P < 0.001). No significant differences in the controllability of the anaesthesia depth, anaesthesia and surgery characteristics, or vital signs were observed between the groups. CONCLUSION Remimazolam demonstrated noninferior efficacy to propofol combined with remifentanil and cisatracurium for TIVA in patients undergoing urological surgery. TRIAL REGISTRATION Chictr.org.cn, identifier: ChiCTR2100050923. CLINICAL REGISTRATION The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100050923, Principal investigator: Xuehai Guan, Date of registration: 8 November 2021, https://www.chictr.org.cn/showproj.html?proj=133466).