Clinical adaptation of a pharmacokinetic model of Propofol plasma concentrations in children

Abstract

Background: A previously published pharmacokinetic simulation suggested a simple manual infusion regimen to achieve propofol plasma concentrations of 3 microg.ml(-1). This study investigated if a simple variation in propofol infusion rates is able to achieve distinct propofol plasma concentrations and whether these are close to the propofol plasma concentrations predicted by the Kataria model.

Methods: With Research Ethics Board approval and written parental consent, a total of 17 healthy children requiring general anaesthesia were enrolled. Following inhalational induction of anaesthesia, a propofol bolus of 5 mg.kg(-1) was given and anaesthesia maintained using an adaptation of the McFarlan continuous propofol infusion regimen to achieve three distinct depths of propofol anaesthesia. Weight and propofol infusion data were used to calculate simulated propofol concentrations using the Kataria dataset and the TIVA simulation program. The performance of the infusion regimen was assessed by calculating the median performance error, median absolute performance error, wobble, and divergence.

Results: Measured propofol concentrations were (mean +/- sd) 7.15 +/- 1.4, 4.3 +/- 0.85, and 2.85 +/- 0.53 microg.ml(-1) against simulation values of 6.6, 4.1, and 2.8 microg.ml(-1), respectively, at 30, 50, and 70 min using the Kataria dataset. These differences were not significant. Formal assessment of the infusion regimen's performance was acceptable.

Conclusion: The manual propofol infusion regimen achieved three distinct depths of propofol anaesthesia. The manual infusion regimen produced higher plasma propofol concentrations than predicted during the early part of the infusion period but was more accurate for later time points.