Temporal characteristics of remimazolam-induced sedation in paediatric anaesthesia: a reply

We appreciate the insightful commentary from Li et al. [1]. In our multicentre trial, the median time to loss of consciousness during induction of anaesthesia was 45 s and 25 s, for children aged 3–6 y receiving 0.3 mg.kg^-1 remimazolam vs. 2.5 mg.kg^-1 propofol, respectively [2]. Although the pharmacokinetic simulation from Li et al. suggests increased drug efficacy, our findings regarding time to loss of consciousness were consistent with previous paediatric research [3]. The use of remimazolam monotherapy for anaesthetic induction did indeed necessitate higher doses [4]. Notably, opioid co-administration can reduce the dose of sedative drugs, and our protocol for anaesthesia induction included intravenous administration of 3 μg.kg^-1 fentanyl 3 min before injection of the study drugs. Consequently, we observed a Modified Observer's Assessment of Alertness/Sedation score of 3 or 2 in some patients before injection of the study drugs. This sequential approach was designed specifically to synchronise tracheal intubation with the peak opioid analgesic effect, accounting for known pharmacokinetic variability in paediatric populations.

Regarding the methods, our protocol mandated randomised administration of initial bolus doses; an injection duration < 60 s; and a standardised assessment of loss of consciousness with no response to gentle shoulder shaking. Consequently, establishing robust temporal pharmacokinetic-pharmacodynamic models between sedative drug administration and loss of consciousness through covariate-adjusted analyses (e.g. age, sex and BMI) using both linear and logistic regression approaches is crucial in optimising safe and effective anaesthetic induction in paediatric anaesthesia.