Effective doses of remimazolam and esketamine combined with remifentanil for endotracheal intubation without muscle relaxants in pediatric patients.

Abstract

Introduction: The combination of remimazolam and esketamine effectively alleviates adverse hemodynamic effects, such as tachycardia and hypertension, during intubation. However, the dosage for achieving optimal intubation conditions when co-administered with remifentanil remains unestablished. Therefore, this study aimed to determine the effective doses of remimazolam and esketamine for endotracheal intubation without muscle relaxants in pediatric patients using Dixon's up-and-down method.

Methods: This prospective, non-controlled, non-randomized clinical trial sequentially allocated 41 children aged 3-6 into two phases. All patients underwent tracheal intubation under general anesthesia. Patients received a fixed dose of remifentanil at 2.5 μg/kg via a pump over 90 s. In the first phase, the induction dose of remimazolam was set at 0.2 mg/kg. The first patient received esketamine at a dose of 0.5 mg/kg, administered with a dose gradient of 0.2 mg/kg based on Dixon's up-and-down method. 50% effective dose (ED₅₀) and 95% effective dose (ED₉₅) for esketamine were then measured through probit regression analysis. Similarly, in the second phase, the ED₉₅ of esketamine was fixed. The first patient received remimazolam at a dose of 0.2 mg/kg, administered at a dose gradient of 0.1 mg/kg. ED₅₀ and ED₉₅ for remimazolam were then measured. Intubation conditions were assessed via the Copenhagen scale. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the following time points: Just before intubation (T1) and 1 min after intubation (T2). Adverse events were also recorded during anesthesia induction.

Results: At a fixed dose of remifentanil (2.5 μg/kg), the ED₅₀ of esketamine was 0.74 mg/kg (95% confidence interval [CI]: 0.61-0.89 mg/kg), while the ED₉₅ was 0.97 mg/kg (95% CI: 0.85-1.75 mg/kg). The ED₅₀ of remimazolam was 0.39 mg/kg (95% CI: 0.29-0.53 mg/kg), while the ED₉₅ was 0.56 mg/kg (95% CI: 0.46-1.47 mg/kg). Hemodynamic stability was maintained during anesthesia induction, with no significant adverse events observed.

Conclusion: The ED₅₀ and ED₉₅ values of remimazolam and esketamine in this study provide initial dosing references for pediatric endotracheal intubation without muscle relaxants. A fixed dose of 2.5 μg/kg remifentanil combined with these agents is safe and effective in children aged 3-6 years, though further multicenter studies are recommended for validation.

Clinical trial registration: www.chictr.org.cn, number: ChiCTR2200063847.