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

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 falling 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.

Thiopentone levels during cardiopulmonary bypass. Changes in plasma protein binding during continuous infusion.

Plasma total and unbound concentrations of thiopentone were investigated during exponentially decreasing infusions in seven patients undergoing cardiopulmonary bypass. Total plasma thiopentone concentrations reached a plateau (10.2, SD 2.1 micrograms/ml) soon after the initial bolus dose and commencement of the infusion. Concentrations were maintained until the onset of cardiopulmonary bypass, whereupon total plasma thiopentone concentration fell abruptly to 50.0 (SD 5.8) percent of the prebypass level. The unbound fraction of thiopentone increased from 16.6 (SD 1.9) percent before bypass to a maximum of 29.3 (SD 5.6) percent during bypass (p less than 0.01), decreased to 22.9 (SD 3.3) percent at the end of bypass (p less than 0.01), but was still elevated 5-7 hours later (20.5, SD 2.5 percent). The result of the changes in binding was a smaller decline in unbound thiopentone concentration at the onset of bypass to 76.4 (SD 15.7) percent of the prebypass level. Also, unbound levels returned to the prebypass level by the end of bypass, whereas total levels remained low.