Pharmacokinetics and effects of propofol 6% for short-term sedation in paediatric patients following cardiac surgery.

Abstract

This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. Six mechanically ventilated children aged 1-5 years received a 6 h continuous infusion of propofol 6% at the rate of 2 or 3 mg kg-1 h-1 for sedation following cardiac surgery. A total of seven arterial blood samples was collected at various time points during and after the infusion in each patient. Pharmacokinetic modelling was performed using NONMEM. Effects were assessed on the basis of the Ramsay sedation score as well as a subjective sedation scale. The data were best described by a two-compartment pharmacokinetic model. In the model, body weight was a significant covariate for clearance. Pharmacokinetic parameters in the weight-proportional model were clearance (CL) = 35 ml kg-1 min-1, volume of central compartment (V1) = 12 l, intercompartmental clearance (Q) = 0.35 l min-1 and volume of peripheral compartment (V2) = 24 l. The interindividual variabilities for these parameters were 8%, < 1%, 11% and 35%, respectively. Compared with the population pharmacokinetics in adults following cardiac surgery and when normalized for body weight, statistically significant differences were observed the parameters CL and V1 (35 vs 29 ml kg-1 min-1 and 0.78 vs 0.26 l kg-1P < 0.05), whereas the values for Q and V2 were similar (23 vs 18 ml kg-1 min-1 and 1.6 vs 1.8 l kg-1, P > 0.05). In children, the percentage of adequately sedated patients was similar compared with adults (50% vs 67%) despite considerably higher propofol concentrations (1.3 +/- 0.10 vs 0.51 +/- 0.035 mg l-1, mean +/- s.e. mean), suggesting a lower pharmacodynamic sensitivity to propofol in children. In children aged 1-5 years, a pharmacokinetic model for propofol was described using sparse data. In contrast to adults, body weight was a significant covariate for clearance in children. The model may serve as a useful basis to study the role of covariates in the pharmacokinetics and pharmacodynamics of propofol in paediatric patients of different ages.