Safety and Efficacy of Remimazolam Tosilate for General Anaesthesia in Paediatric Patients Undergoing Elective Surgery: a Multicentre, Randomised, Single-blind, Controlled Trial

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative drug. This study aimed to compare the efficacy and safety of remimazolam with propofol for induction and maintenance of general anaesthesia in children undergoing elective surgery.

Methods: Children (aged 3-6 y, ASA physical status 1 or 2, BMI 14-25 kg.m) undergoing elective surgery under general anaesthesia with tracheal intubation were eligible for inclusion. Children were allocated randomly using a web-based system to receive either remimazolam or propofol in a 3:1 ratio. After receiving fentanyl 3 μg.kg, children received their allocated drug for both induction and maintenance of general anaesthesia. Induction doses were remimazolam 0.3 mg.kg or propofol 2.5 mg.kg, with a second dose given should they not achieve loss of consciousness. After neuromuscular blockade and tracheal intubation, maintenance anaesthesia was achieved with an infusion either remimazolam 1-3 mg.kg.h or propofol 4-12 mg.kg.h, alongside a remifentanil infusion (0.1-0.5 μg.kg.min) titrated to surgical stimulus and haemodynamic parameters. Primary outcomes were the incidence of successful induction and maintenance of anaesthesia. Secondary outcomes included: time to loss of consciousness, awakening and tracheal extubation; incidence of emergence delirium and moderate or severe pain in post-anaesthesia care unit; incidence of negative behaviour change after surgery at postoperative day 3; and incidence of adverse events.

Results: A total of 187 children were analysed (140 allocated to remimazolam and 47 to propofol). All children achieved successful induction of anaesthesia. Successful maintenance of anaesthesia was achieved in 139 (99%) children who received remimazolam compared with 46 (98%) who received propofol (rate difference 1.4%, 95%CI -2.9-5.8%, p = 0.441). Adverse events occurred in 27 (19%) children who received remimazolam and 23 (49%) who received propofol.

Discussion: Remimazolam was well tolerated for the induction and maintenance of general anaesthesia in pre-school-age children and was non-inferior to propofol.