Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children

The performance of eight currently available paediatric propofol pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in healthy children from 3 to 26 months of age.

Forty-one, ASA I-II children, aged 3-26 months were studied. After the induction of general anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg kg(-1) followed by an infusion of 8 mg kg(-1) h(-1) was given. Arterial blood samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion. Model performance was visually inspected with measured/predicted plots. Median performance error (MDPE) and the median absolute performance error (MDAPE) were calculated to measure bias and accuracy of each model.

Performance of the eight models tested differed markedly during the different stages of propofol administration. Most models underestimated propofol concentration 1 min after the bolus dose, suggesting an overestimation of the initial volume of distribution. Six of the eight models tested were within the accepted limits of performance (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed best.

Our results suggest that six of the eight models tested perform well in young children. Since most models overestimate the initial volume of distribution, the use for TCI might result in the administration of larger bolus doses than necessary.