Propofol is a commonly used intravenous sedative and general anesthetic, with rapid onset and short duration of action. It has a narrow therapeutic index and significant interindividual variability in dosing requirements, which may elevate risks of its use, particularly in children. We aimed to quantify the doses required to induce loss of consciousness and apnea in children by age and sex to contribute to tailored propofol dosing recommendations for improved safety and efficacy in pediatric anesthesia. In this stratified- and purposive-sampling study, we enrolled children in six groups based on sex and age (3- to 5-year-olds, 6- to 10-year-olds, 11- to 18-year-olds), targeting 60 participants per group. For induction of anesthesia, we administered propofol at a constant rate until apnea was reached (absence of end-tidal CO2 for 20 s) up to a maximum dose of 10 mg/kg. We measured the propofol dose required to reach pharmacodynamic endpoints, including loss of eyelash reflex (LOER) and apnea, and estimated the effect of sex and age on these doses. Data were available for 318 participants, with 162 females and a median (interquartile range) age of 8.1 (5.3-12.9) years. The mean (SD) propofol dose to LOER was 2.65 (0.69) mg/kg with no effect of sex (-0.10 mg/kg for male, 95% confidence interval (CI) -0.26 to 0.05, p = 0.183) or age (0.0 mg/kg per year, 95% CI -0.02 to 0.02, p = 0.876). The mean (SD) propofol dose to apnea was 6.82 (1.64) mg/kg, with significant effects of both sex (+0.67 mg/kg for male, 95% CI 0.30 to 1.03, p < 0.001) and age (-0.14 mg/kg per year, 95% CI -0.19 to -0.1, p < 0.001). Apnea was not reached in 62 participants. Older and female children exhibited narrower therapeutic indices for the margin between LOER and apnea. This requires heightened vigilance, especially when maintaining spontaneous respiration. A planned genome-wide association study may identify pharmacogenetic-pharmacodynamic relationships and correlations with genetic ancestry. The trial was registered on clinicaltrials.gov before enrolment (NCT04164264; date of registration 2019-11-15).
Moxham et al. (Mon,) studied this question.