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.