Propofol sequestration within the extracorporeal circuit

Various drugs administered during cardiac anaesthesia are sequestered in the extracorporeal circuit in vitro, but it is uncertain whether this sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (1) in vitro sequestration of propofol in the extracorporeal circuit and (2) whether the change in plasma propofol concentration induced by initiation of cardiopulmonary bypass in vivo can be explained by haemodilution. For the in vitro evaluation, three separate experiments with a closed circuit (membrane oxygenator, reservoir, and tubings) were performed. The pH and PCO₂ of the circulating solution (a mixture of Ringer’s acetate and whole blood) were maintained within the normal physiological range, and the temperature of the solution was 28° C. The solution was circulated at a flow of 4 L · min^?1 and propofol was added to the solution to achieve a concentration of 2 μg · ml^?1. Serial samples were taken from the circulating solution for measurement of propofol concentration by high performance liquid chromatography. In the in vivo part of the study, 14 patients received a continuous infusion of propofol, and samples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiation of cardiopulmonary bypass. In vitro, at 5 and 120 min after addition of propofol into the circulating solution, approximately 65% and 25%, respectively, of the predicted propofol level was measurable in the solution. In vivo, five minutes after initiation of the cardiopulmonary bypass plasma propofol concentration decreased (P < 0.001) more (from 2.8 ±0.7 (mean ± SD) to 1.5 ± 0.5 μg · ml^?1, a 45 ± 12% decrease) than would have been predicted on the basis of acute haemodilution (a decrease in haematocrit from 0.39 ± 0.04 to 0.28 ± 0.03 is a 29 ± 4% decrease). Ten minutes after initiation of cardiopulmonary bypass, plasma propofol concentration was 1.6 ± 0.5 μg · ml^?1 (a 37 ± 27% decrease from the pre-bypass level) and haematocrit was 0.27 ± 0.04 (a 30 ± 6% decrease): the decrease in plasma propofol concentration was not different from the decrease observed in the haematocrit. In conclusion, propofol is markedly sequestered within the extracorporeal circuit in vitro. This sequestration may, to some extent, affect plasma propofol concentration in vivo.