The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental

Abstract

The effects of cardiopulmonary bypass (CPB) on plasma concentrations and protein binding of methohexital and thiopental were studied during continuous infusions in two groups of ten cardiac surgical patients. Patients were administered an infusion regimen designed to produce a stable total plasma concentration at 5 mg/L for methohexital and 10 mg/L for thiopental. Prior to the commencement of CPB the mean (±SD) total plasma methohexital concentration was 5.00 ± 0.69 mg/L. This fell to 3.12 ± 0.89 mg/L at two minutes after commencement of CPB, and rose to 4.67 ± 1.11 mg/L by 75 minutes after commencement of CPB. The unbound fraction rose from 27.1 ± 5.1% to 42.8 ± 9.2% at five minutes after the start of CPB, and gradually decreased to 32.1 ± 4.9% by 75 minutes. The unbound concentration (1.37 ± 0.32 mg/L) was unaffected by the onset of CPB, being 1.51 ± 0.49 mg/L at 75 minutes after the start of CPB. Thiopental followed a similar pattern to methohexital, with the total plasma thiopental concentration failing from 9.22 ± 0.73 mg/L to 4.90 ± 0.83 mg/L at two minutes after commencement of CPB, and rising again to 7.13 ± 1.03 mg/L 75 minutes later. During the same period the unbound fraction of thiopental rose from 16.1 ± 2.5% to 30.3 ± 7.3% five minutes after the start of CPB, and fell gradually to 22.8 ± 5.8% after 75 minutes. The unbound concentration (1.51 ± 0.21 mg/L) was again unchanged by the onset of CPB, being 1.71 ± 0.29 mg/L at 75 minutes. Plasma protein binding of both drugs correlated strongly with plasma albumin concentration, which decreased by 40% during CPB. It is concluded that hemodilution caused the reduction in total drug concentration and protein binding at the onset of CPB, but that the decrease in protein binding counteracted the dilution of unbound drug, resulting in a stable unbound concentration throughout CPB, and that this effect may be common for barbiturates.