| Background: Propofol, a rapidly acting intravenous anesthetics, which is widely used for anesthetic induction and maintainance, and also for sedation during local and regional anesthesia, as well as outside the operating room(i.g., intensive care unit[ICU]). It has a large volume of distribution and a high total body clearance. It is supposed to be metabolized mainly in liver and probably in other organs by foreign researches, but find few of the similar reports in the home references. Liver transplantation including three phase: pre-anhepatic phase (or liver dissection phase), anhepatic phase and hepatic reperfusion phase. The anhepatic phase of liver transplantation provides a uniquely usefull tool to study the extrahepatic metabolism of drugs. The purpose of this study was to observe the changes of propofol blood concentrations both in the radial artery and in the pulmonary artery at different times and to confirm the extrahepatic metabolism of propofol and to show the effect of lungs for propofol in the extrahepatic metabolism and to evaluate the meanings during orthotopic liver transplantation (OLT) with non-veno-venous bypass.Methods: 15 patients undergoing orthotopic liver transplantation with non-veno-venous bypass, ASA grade III -IV, male 12, female 3, mean age 46.6(SD 2.1) yr, mean weight 62.2(SD 3.0) kg. Before induction of anesthesia, two 14-gauge or 16-gauge cannulas were inserted in the large vein of forearm , one only for the infusion of propofol and the other for liquid infusion. Two 20-gauge cannulas were inserted in the bilateral radial artery, one for blood pressure monitoring and the other for blood sampling. A large-bore intravenous cannula was inserted in the right internal jugular vein and a pulmonary artery catheter was passed into the pulmonary artery for pulmonary blood pressure(PAP) monitoring and blood sampling. Anesthesia was induced by combining with midazolam 0.05 mg.kg-1, scopolamine 0.006 mg.kg-1, etomidate 0.3 mg.kg-1, fentanyl 4-6 μg.kg-1 and vecuronium 0.1 mg.kg-1. After trachea intubation, the pure oxygen was supplied to artificial ventilation and the ventilation parameters were adjusted in time to maintain the end-tidal carbon dioxide partial pressure(PETCO2) at 30-45mmHg. Anesthesia was maintained with infusion of propofol at the rate of 2 mg.kg-1.h-1 via a forearm vein combined with midazolam , fentanyl and vecuronium. The propofol infusion rate was kept constant throughout the operation. Blood samples(3ml) for propofol analysis were taken simultaneously from the radial artery and the pulmonary artery at the following times: hepatic dissociation(dissociation of the first hepatic portal) , immediatedevascularization of the portal vein , 30min and 60min post-devascularization of the portal vein, 30min and 60min and 120min post-reperfusion of the portal vein. Each sample was thoroughly mixed in tube containing liquaemin sodium, then centrifugalized, after that the plasma was got and stored in the refrigerator at 4℃. The plasma propofol concentrations were determined by high performance liquid chromatography (H.P.L.C) with fluorescence detection.Results: The average time of orthotopic liver transplantation with non-veno-venous bypass (n=15) was 452(SD20)minutes, including pre-anhepatic phase 169(SD11.3) minutes, anhepatic phase 73(SD3.2) minutes, hepatic reperfusion phase 208(SD16.7) minutes. The blood concentrations of propofol both in the radial artery and in the pulmonary atery rose sharply after the devascularization of the potal vein. At the times: 30min[radial artery(RA): 1.966 (SD0.755) μg.ml-1], pulmonary atery(PA):2.159 (SD1.364) μg.ml-1] and 60min[RA: 2.061 (SD0.788) μg.ml-1,PA: 2.099 (SD0.785) μg.ml-1] post devascularization of the potal vein ,the propofol blood concentrations both in the radial artery and in the pulmonary artery were significantly higher than that at any other times(P<0.01). The propofol blood concentrations both in the radial artery and in the pulmonary atery, between at the 30 min and 60 min post... |
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