Abstract
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.
Résumé
Cette étude vise à déterminer I) l’importance de la séquestration in vitro du propofol dans le circuit de circulation extracorporelle (CEC) et 2) si l’hémodilution seule peut expliquer in vivo les changements de concentration plasmatique qui surviennent après l’initiation de la CEC. Pour l’étude in vitro, trois expériences en circuit fermé séparées (oxygénateur à membrane, réservoir et tubulures) sont effectuées. Le pH et la PCO2 de la solution circulée sont maintenus dans les limites de la normale physiologique avec une température de 28° C. La solution circule avec un débit de 4 L · min−1 et du propofol est ajouté à la solution pour obtenir une concentration de 2 μg · ml−1. Des échantillons en série sont prélevés pour la mesure de la concentration du propofol par Chromatographie en phase liquide à haute performance. Pour l’étude in vivo, 14 patients reçoivent du propofol en perfusion continue et des échantillons sont prélevés pour déterminer la concentration plasmatique de propofol et l’hématocrite à cinq et dix minutes après le début de la CEC. In vitro, à 5 et 120 min après l’ajout du propofol dans la solution circulée, environ 65% et 25% respectivement du niveau de propofol prédit sont mesurables dans la solution. In vivo, cinq minutes après l’initiation de la CEC, la concentration plasmatique de propofol diminue (P < 0,001) à un degré plus considérable (de 2,8 ± 0,7 moyenne ± SD à 1,5 ± 0.5 μg · ml−1, une baisse de 45 ± 12%) qu’on pouvait le prédire sur la base de l’hémodilution aiguë (une baisse de l’hématocrite de 0,39 ± 0,04 à 0,28 ± 0,03, soit une baisse de 29 ± 4%). Dix minutes après l’initiation de la CEC, la concentration plasmatique de propofol est de 1,6 ± 0,5 μg · ml−1 (une baisse de 37 ± 27% du niveau pré-CEC) et l’hématocrite se situe à 0,27 ± 0,04 (une baisse de 30 ± 6%); la baisse de la concentration plasmatique de propofol n’est pas différente de la baisse de l’hématocrite. En conclusion, la séquestration in vitro du propofol dans le circuit de CEC est considérable. Cette séquestration peut affecter jusqu’à un certain point la concentration de propofol in vivo.
Article PDF
Similar content being viewed by others
References
Russell GN, Wright EL, Fox MA, Douglas EJ, Cockshott ID. Propofol-fentanyl anaesthesia for coronary artery surgery and cardiopulmonary bypass. Anaesthesia 1989; 44: 205–8.
Massey NJA, Sherry KM, Oldroyd S, Peacock JE. Pharmacokinetics of an infusion of propofol during cardiac surgery. Br J Anaesth 1990; 65: 475–9.
Hall RI, Murphy JT, Moffitt EA, Landymore R, Pollak PT, Poole L. A comparison of the myocardial metabolic and haemodynamic changes produced by propofolsufentanil and enflurane-sufentanil anaesthesia for patients having coronary artery bypass graft surgery. Can J Anaesth 1991; 38: 996–1004.
Underwood SM, Davies SW, Feneck RO, Walesby RK. Anaesthesia for myocardial revascularisation. A comparison of fentanyl/propofol with fentanyl/enflurane. Anaesthesia 1992; 47: 939–45.
Searle NR, Sahab P. Propofol in patients with cardiac disease. Can J Anaesth 1993; 40: 730–47.
Hynynen M, Takkunen O, Salmenperä M, Haataja H, Heinonen J. Continuous infusion of fentanyl or alfentanil for coronary artery surgery. Plasma opiate concentrations, haemodynamics and postoperative course. Br J Anaesth 1986; 58: 1252–9.
Morgan DJ, Crankshaw DP, Prideaux PR, Chan HNJ, Boyd MD. Thiopentone levels during cardiopulmonary bypass. Changes in plasma protein binding during continuous infusion. Anaesthesia 1986; 41: 4–10.
Cockshott ID, Briggs LP, Douglas EJ, White M. Pharmacokinetics of propofol in female patients. Studies using single bolus injections. Br J Anaesth 1987; 59: 1103–10.
Dasta JF, Jacobi J, Wu LS, et al. Loss of nitroglycerin to cardiopulmonary bypass apparatus. Crit Care Med 1983; 11: 50–2.
Hynynen M. Binding of fentanyl and alfentanil to the extracorporeal circuit. Acta Anaesthesiol Scand 1987; 31: 706–10.
Hynynen M, Olkkola KT, Näveri E, Palojoki R, Neuvonen PJ, Heinonen J. Thiopentone pharmacokinetics during cardiopulmonary bypass with a nonpulsatile or pulsatile flow. Acta Anaesthesiol Scand 1989; 33: 554–60.
Rosen DA, Rosen KR, Silvasi DL. In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 1990; 4: 332–5.
Tarr TJ, Kent AP. Sequestration of propofol in an extracorporeal circuit (Abstract). J Cardiothorac Anesth 1989; 3 (Suppl 1): 75.
Buylaert WA, Herregods LL, Mortier EP, Bogaert MG. Cardiopulmonary bypass and the pharmacokinetics of drugs. An update. Clin Pharmacokinet 1989; 17: 10–26.
Hall R. The pharmacokinetic behaviour of opioids administered during cardiac surgery. Can J Anaesth 1991; 38: 747–56.
Hynynen M, Hynninen M, Soini H, Neuvonen PJ, Heinonen J. Plasma concentration and protein binding of alfentanil during high-dose infusion for cardiac surgery. Br J Anaesth (in press).
Kamath BSK, Thomson DM, Johnston B. Administration of drugs during cardiopulmonary bypass. An analysis of the fate of a bolus injected through different routes using radio-active technetium. Anaesthesia 1980; 35: 908–13.
Cockshott ID, Douglas EJ, Plummer GF, Simons PJ. The pharmacokinetics of propofol in laboratory animals. Xenobiotica 1992; 22: 369–75.
Author information
Authors and Affiliations
Additional information
This study was supported in part by a research grant from the Paulo Foundation, Finland. Zeneca Pharma, Finland, has supplied financial support for thein vitro experiments.
Rights and permissions
About this article
Cite this article
Hynynen, M., Hammarén, E. & Rosenberg, P.H. Propofol sequestration within the extracorporeal circuit. Can J Anaesth 41, 583–588 (1994). https://doi.org/10.1007/BF03009997
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03009997