Pharmacokinetics Of Propofol Administered By Target-controlled Infusion To Patients With Different Hepatic Function

Background: Propofol was an intravenous anesthetic agent which was employed widely in clinical practice. While hepatic metabolism was considered as the main elimination pathway of propofol. The patients with hepatic dysfunction were frequently presented for anesthesia and surgery. Whether there were changes in pharmacokinetics under this condition were not entirely known. Target-controlled infusion was an intravenous infusion system controlled by computer, it could keep the induction and maintenance of anesthesia stability. This study was designed to investigate the influence of different liver function on propofol pharmacokinetics.Methods: Twenty-seven patients aged 22-59yr, weighing 46-81kg, undergoing elective surgery procedures were divided into A, B, C three groups(n = 9/group) according to the Child-Pugh classification. All patients received propofol by target-controlled infusion. The TCI system consisted of (1) Graseby 3500 infusion pump, (2) pharmacokinetic parameters developed by Marsh. Target plasma concentration of propofol was set at 2.5ug/ml. TCI of propofol lasted 60min, blood samples were obtained before induction of anesthesia and at 2, 5, 10, 20, 30, 40, 50, 60, 62.5, 65, 70, 75, 80, 85, 90minafter TCI was started for determination of plasma propofol concentration by gas chromatography-mass spectrometry method. Pharmacokinetic parameters were assessed using DAS program and analyzed using SPSS program. Results: The demographics and total amount of propofol did not differ among the three groups, Significant differences could be obtained in total bilirubin, cholesterol, albumin, prothrombin time among three groups, total bilirubin , prothrombin time were the highest and cholesterol, albumin were the lowest in group C than those in group A and B. The half-time in three groups was: group A: Ti/2ce= 0.03lh, Tmp= 0.440h,, group B: Tmce= 0.040h, Tml3= 0.577h. group C: Ti/2o= 0.030h, Ti/2^= 0.591h. No differences could be obtained of the half-time among the three groups. The volume of central compartment was : group A: Vl= 1.77 L/kg, group B: Vl= 2.899L/kg, group C: Vl= 7.076L/kg. The volume of peripheral compartment was: group A: V2= 6.14L/kg, group B: V2= 7.721 L/kg, group C: V2= 20.52 L/kg. The volume of central and peripheral compartment were greater in group C than those in group A and B. The clearance in three geoups was : group A: CL= 9.816L/h/kg, group B: CL= 7.273L/h/kg, group C: CL= 24.04 L/h/kg. The clearance was greater in group C than those in group A and B . Conclusion: Propofol showed very large volumes of distribution in patients with liver failure, and the increase of plasma propofol concentration become slow, which made the onset time of propofol prolonged, these were related to changes of internal environment present in patients with liver failure. Although the larger volumes of distribution in patients with liver failure, there was no influence in clearance. So it could not cause accumulation and prolong the action time of propofol.