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 th is sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (I) in vitro sequestrati on of propofol in the extracorporeal circuit and (2) whether the chang e in plasma propofol concentration induced by initiation of cardiopulm onary bypass in vivo can be explained by haemodilution. For the in vit ro evaluation three separate experiments with a closed circuit (membra ne 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 degrees C. The solution was circula ted at a flow of 4 L.min(-1) and propofol was added to the solution to achieve a concentration of 2 mu g.ml(-1). Serial samples were taken f rom 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 sa mples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiati on of cardiopulmonary bypass. In vitro, at 5 and 120 min after additio n of propofol into the circulating solution, approximately 65% and 25% , respectively, of the predicted propofol level war measurable in the solution. In vivo, five minutes after initiation of the cardiopulmonar y bypass plasma propofol concentration decreased (P < 0.001) more (fro m 2.8 +/- 0.7 (mean +/- SD) to 1.5 +/- 0.5 mu g.ml(-1), a 45 +/- 12% d ecrease) than would have been predicted on the basis of acute haemodil ution (a decrease in haematocrit from 0.39 +/- 0.04 to 0.28 +/- 0.03 i s a 29 +/- 4% decrease). Ten minutes after initiation of cardiopulmona ry bypass, plasma propofol concentration was 1.6 +/- 0.5 mu g.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 c oncentration was not different from the decrease observed in the haema tocrit. In conclusion, propofol is markedly sequestered within the ext racorporeal circuit in vitro. This sequestration may, to some extent, affect plasma propofol concentration in vivo.