Changes in apparent systemic clearance of propofol during transplantation of living related donor liver.
BACKGROUND
Propofol is used during living-related donor liver transplantation because its metabolism is not greatly affected by liver failure. However, the pharmacokinetics of propofol during liver transplantation have not been fully defined. The purpose of this study was to evaluate the apparent systemic clearance of propofol during the dissection, anhepatic and reperfusion phases of living-related donor liver transplantation, and to estimate the role of the small intestine and lung as extrahepatic sites for propofol disposition.


METHODS
Ten patients scheduled for living-related donor liver transplantation were enrolled in the study. Anaesthesia was induced with vecuronium 0.1 mg kg(-1) and propofol 2 mg kg(-1), and then maintained by 60% air, 0.5-1.5% isoflurane in oxygen and a constant infusion of propofol at 2 mg kg(-1) h(-1). Apparent systemic clearance during the dissection, anhepatic and reperfusion phases was calculated from the pseudo-steady-state concentration for each phase. Disposition in the small intestine was determined by measuring arteriovenous blood concentration in 10 liver transplantation donors. Pulmonary disposition was determined by measuring the arteriovenous blood concentration in 10 recipients during the anhepatic phase. The data are expressed as mean (sd).


RESULTS
Apparent systemic clearances in the dissection, anhepatic and reperfusion phases were 1.89 (sd 0.48) litre min(-1), 1.08 (0.25) litre min(-1) and 1.53 (0.51) litre min(-1), respectively. The concentration of propofol in the portal vein was lower than in the radial artery. The intestinal extraction ratio calculated from the concentration in the radial artery and portal vein was 0.24 (0.12). There were no significant differences in propofol concentrations between the radial and pulmonary arteries.


CONCLUSIONS
Apparent systemic clearance was decreased by approximately 42 (10)% during the anhepatic phase compared with the dissection phase. After reperfusion, liver allografts rapidly began to metabolize propofol. The small intestine also participates in the metabolism of propofol.
Takizawa
D
D
Department of Anesthesiology, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan. d-takiza@bf6.so-net.ne.jp
Sato
E
E
Hiraoka
H
H
Tomioka
A
A
Yamamoto
K
K
Horiuchi
R
R
Goto
F
F
D000328:Adult; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D008168:Lung / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015742:Propofol / Q000493:pharmacokinetics*; D014019:Tissue Donors
D018686:Anesthetics, Intravenous; D015742:Propofol