Age-Specific Plasma Concentration, Efficacy and Safety of Ciprofol (Cipepofol) for Induction and Maintenance of General Anesthesia in Pediatric Patients Undergoing Elective Surgery: A Single-Arm Prospective, Pragmatic Trial.

Abstract

Background and objective: Ciprofol (Cipepofol) currently has well-established clinical research data in adult Chinese patients, but there is a lack of reliable research data in pediatric patients. This study aimed to assess the age-specific plasma concentration, efficacy and safety profiles of cipepofol in pediatric patients aged 2-17 years during the induction and maintenance of general anesthesia.

Methods: This was a single-arm, open-label, prospective, pragmatic study conducted in the Hunan Children's Hospital from May 10, 2023 to August 25, 2023, that involved pediatric patients undergoing elective surgery after the induction and maintenance of general anesthesia. Cipepofol was administered as an intravenous bolus injection of 0.6 mg/kg (patients aged 2-11 years) or 0.5 mg/kg (12-17 years) for induction, followed by an initial maintenance infusion of 1.2 mg/kg/h or 1.4 mg/kg/h, respectively. The primary endpoint-plasma concentration of cipepofol was measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The age-specific plasma concentration, efficacy and safety profiles of cipepofol are summarized using descriptive statistics.

Results: All 38 enrolled patients completed the study, including 14 children aged 2-5 years, 12 children aged 6-11 years and 12 children aged 12-17 years. The trends of plasma concentration variations among patients in the three age groups were largely consistent. The success rates of anesthesia induction and maintenance for patients in the three groups were both 100%, and no patients required rescue medication. Children aged 2 to 5 years had the longest median durations of successful anesthetic induction (1.1 min) and eyelash reflection disappearance (1.2 min), while the median durations for patients aged 6-11 years and those aged 12-17 years (0.5 and 0.5 min) were similar. The median time to extubation and length of stay in the post-anesthesia care unit tended to be the longest in children aged 6-11 years (23.5 and 30.0 min) but were comparable for those aged 2-5 years (10.5 min and 20.0 min) and 12-17 years (11.0 and 20.0 min). The median time to full alertness tended to decrease with increasing age (33.7 vs 25.8 vs 22.7 min). A total of 4 (10.5%) patients experienced treatment-emergent adverse events in those aged 2-5 years or 12-17 years, with a severity of grade 1 or grade 2.

Conclusion: Cipepofol had good safety for the induction and maintenance of general anesthesia in pediatric patients aged over 2 years. The dosing regimen with an intravenous bolus injection of 0.5 mg/kg for induction, followed by an initial maintenance infusion of 1.4 mg/kg/h was adequate for children aged 12-17 years; age-specific dose regimen for children aged 2-11 years should be improved by further large-scale prospective studies.

Trial registration: ChiCTR2400085640, July 14, 2024, retrospectively registered.