External Validation of a Pharmacokinetic-Pharmacodynamic Model of Propofol for Target-Controlled Infusion in Children Under Two Years of Age

Abstract

Background: Previously, a linked pharmacokinetic-pharmacodynamic model (Kim model) of propofol was developed for children aged 2 to 12 years, allowing target-controlled infusion. Despite an increasing need for intravenous anesthesia using propofol during surgery in children younger than two years of age, no pharmacokinetic-pharmacodynamic model of propofol has been developed for this population. Therefore, in this study, we performed an external validation of Kims propofol model for children aged less than two years. Methods: Twenty-four children below the age of two years undergoing neurosurgery were enrolled. Anesthetic induction was commenced using a target-controlled infusion of 2% propofol based on Kim model and continuous infusion of remifentanil under bispectral index (BIS) monitoring. The target effect-site concentration of propofol was set to 2, 3, 4, and 5 g/ml, each followed by arterial blood sampling after 10 min of equilibrium. Population estimates of pooled bias, inaccuracy, divergence, and wobble were calculated to evaluate the performance of the Kim model. Results: A total of 95 plasma concentrations and 91 BIS values were used for evaluation of the Kim model. For plasma concentration of propofol, the bias was -0.96% and inaccuracy was 21.0%. For BIS, the bias was -7.7% and inaccuracy was 20.6%. Conclusions: The pooled bias and inaccuracies from the pharmacokinetic-pharmacodynamic predictions were within clinically acceptable range. Therefore, the Kim model may be applicable for propofol target-controlled infusion in children under two years of age.