Population Pharmacokinetics of Propofol in Critically Ill Patients with and Without Extracorporeal Membrane Oxygenation.

BACKGROUND AND

OBJECTIVE

Propofol is commonly used in critically ill patients on extracorporeal membrane oxygenation (ECMO). Although ECMO may theoretically affect drug pharmacokinetics (PK) through various mechanisms, data on propofol PK in this context remain scarce, with only one small recent study available. Our aim was to assess the impact of ECMO on propofol PK in a larger cohort.

METHODS

We conducted a prospective, bicentric observational PK study in critically ill patients with and without ECMO (controls). Critically ill adults receiving a continuous infusion of propofol were eligible for inclusion. Controls were selected to ensure similarity with ECMO patients. We collected a maximum of eight samples per patient over 9 h. We analysed plasma samples using a high-performance liquid chromatography coupled to tandem mass spectrometry validated method. We developed a population pharmacokinetic (popPK) model using a classical stepwise approach with nonlinear mixed effects modelling software.

RESULTS

A total of 40 patients, 20 with and 20 without ECMO, contributed 300 samples. A two-compartment model best described the data, with body weight affecting clearance. ECMO had no substantial impact on propofol PK. The final popPK model parameter estimates with between-subject variability were as follows: clearance 68 L/h (34%), intercompartmental clearance 26 L/h, and central and peripheral volumes of distribution 1.2 L/kg (230%) and 1.4 L/kg, respectively. A proportional error model best described the residual unexplained variability (13%).

CONCLUSIONS

Our popPK analysis shows that propofol PK does not differ between critically ill patients with and without ECMO and confirms a high PK variability in this population.