Pharmacokinetics of Methadone in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Abstract

Cardiopulmonary bypass (CPB) induces profound physiological changes that may alter the pharmacokinetics of methadone. We aimed to describe the pharmacokinetics of an intravenous bolus of methadone racemate in adult patients undergoing heart surgery with CPB. We prospectively studied 29 patients aged 45 to 75 years scheduled for cardiac surgery with CPB who received methadone 0.2 mg/kg after anesthesia induction. Arterial blood samples (n = 10) were taken, before, during, and after CPB. Pharmacokinetic analysis was undertaken using nonlinear mixed effects models. All patients completed the study. The median [interquartile range] methadone concentrations decreased from 34.8 [23.9-48.2] ng/mL (10 minutes before CPB) to 18.2 [9.9-26] ng/mL after 60 minutes of CPB ( P < .001). A 3-compartment model adequately described the observed changes in methadone concentrations. The influence of CPB on methadone pharmacokinetics was best described by hemodilution in a fixed volume of 1.5 L (CPB circuit volume) and by sequestration from the CPB components (CL SEQ = 93.4 L/h, 95%CI 59-124, P < .01). The observed effect of CPB in methadone pharmacokinetics can be compensated by giving a supplementary bolus dose of 0.05 mg/kg at the end of CPB. Our results confirmed a decay in methadone concentrations during CPB, which, in our modeling analysis, was attributed to hemodilution and sequestration within the CPB components.