Pharmacokinetics of propofol after a single dose in children aged 1-3 years with minor burns: Comparison of three data analysis approaches

Background: No complete pharmacokinetic profile of propofol is yet available in children younger than 3 yr, whereas clinical studies have demonstrated that both induction and maintenance doses of propofol are increased with respect to body weight in this age group compared to older children and adults. This study was therefore undertaken to determine the pharmacokinetics of propofol after administration of a single dose in aged children 1-3 yr requiring anesthesia for dressing change. Methods: This study was performed in 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 1296 of total body surface area. Exclusion criteria were: unstable hemodynamic condition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg · kg^-1) plus fentanyl (2.5 μg · kg^-1) was administered while the children were bathed and the burn area cleaned during which the children breathed spontaneously a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 μl were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4, 8, and 12 h after injection; an earlier sample was obtained from 8 of 12 children. The blood concentration curves obtained for individual children were analyzed by three different methods: noncompartmental analysis, mixed-effects population model, and standard two- stage analysis. Results: Using noncompartmental analysis, total clearance of propofol (± SD) was 0.053 ± 0.013 1 · kg^-1 · min^-1, volume of distribution at steady state 9.5 ± 3.7 1 · kg^-1, and mean residence time 188 ± 85 min. Propofol pharmacokinetics were best described by a weight- proportional three-compartmental model in both population and two-stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of population versus two-stage analysis are as follow: systemic clearance 0.049 versus 0.048 l · kg^-1 · min^-1, volume of central compartment 1.03 versus 0.95 l · kg^-1, volume of distribution at steady state 8.09 versus 8.17 l · kg^-1. Conclusions: The volume of the central compartment and the systemic clearance were both greater than all values reported in older children and adults. This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children aged 1-3 yr.