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.