Determination of the 50% and 95% effective dose of esketamine combined with propofol for intravenous sedation in pediatric circumcision: study protocol for a randomized controlled, double-blind, dose-finding clinical trial

Abstract

Background: Pediatric circumcision is a common yet often distressing procedure due to the associated pain and emotional response it can elicit in children. Adequate sedation and analgesia are critical to mitigate these effects and ensure the procedure's success. The combination of propofol and opioids continues to be the most commonly utilized intravenous anesthetic regimen for pediatric circumcision procedures. However, due to its narrow therapeutic index, propofol may cause notable hemodynamic and respiratory depression. Esketamine, an S(+)-isomer of ketamine, is recognized for its analgesic potency and minimal respiratory impact. Furthermore, its sympathomimetic properties offer a counterbalance to the hemodynamic inhibition of propofol. Therefore, the aim of this study is to determine the optimal dose of esketamine combined with propofol for pediatric circumcision.

Methods: This prospective, randomized controlled, dose-finding clinical trial will enroll 100 children aged 3-9 years who undergo circumcision. Participants will be randomly assigned to five groups to receive varying doses of esketamine (0.50, 0.75, 1.00, 1.25, and 1.50 mg/kg) combined with 3 mg/kg propofol for achieving adequate sedation. An effective dose of esketamine will be defined as non-occurrence of physical movement, frowning, or Ramsay Sedation Scale (RSS) score ≥ 5 during skin incision. The values for median effective dose (ED₅₀), 95% effective dose (ED₉₅), and 95% confidence intervals (95% CIs) of esketamine will be determined using probit regression.

Discussion: The results of this study seek to determine the ED₅₀ and ED₉₅ values of esketamine combined with propofol for intravenous sedation in pediatric circumcision using probit regression analysis, which will provide further references for precise medication in pediatric circumcision.

Trial registration: Chinese Clinical Trial Registry ChiCTR2400090035. Registered on September 23, 2024.

Keywords: 95% effective dose; Circumcision; Dose-finding; Esketamine; Median effective dose; Pediatric; Propofol.