[Hepatic elimination of thiopental in heart surgery patients].
Thiopental is a hypnotic drug that is widely used for the induction of anaesthesia. The mechanism of the short-term action is based on the rapid distribution of the drug, and in contrast to methohexital, the metabolism of thiopental is not relevant in use in conditions of operative anaesthesia. However, in neurotraumatology thiopental is frequently used as continuous infusion for several days to reduce cerebral metabolism. Under these circumstances, the elimination of thiopental becomes the most important factor for the duration of action. In order to clarify the relative contribution of the liver to the disposition of thiopental, hepatic blood flow was measured during the induction of anaesthesia and at sternotomy combined with the determination of plasma concentrations of the drug in arterial and hepatic venous blood, making it possible to calculate the hepatic and total plasma clearance of thiopental. METHOD. The study was thoroughly discussed and approved by the local ethics committee, and all patients gave informed written consent. The investigation was performed in 10 male patients (as detailed in Table 1), who had been referred for elective coronary artery bypass surgery. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. Before induction of anaesthesia (MP1), after induction (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Additionally, arterial and hepatic venous plasma concentrations of thiopental were determined by gas chromatography after induction until the extracorporeal circulation was started. Anaesthesia was induced with a bolus dose of thiopental 4 mg/kg body wt, fentanyl 7 micrograms/kg and pancuronium 0.1 mg/kg and maintained with a continuous infusion of fentanyl 20 micrograms/min and mechanical ventilation with O2/N2O at an FiO2 of 0.5. RESULTS. Median arterial pressure (MAP) decreased from 89 mmHg to 74 mmHg after induction and rose again to reach 104 mmHg at sternotomy. Cardiac output (HZV) also decreased from 6.17 l/min to 4.76 l/min after induction, but remained unchanged at sternotomy (Table 2). Hepatic plasma and blood flow showed no significant changes but tended to decrease after the induction of anaesthesia. Hepatic blood flow was constantly 26-28% of cardiac output. In the same way, intestinal oxygen consumption (VO2) did not change significantly, but the tendency was identical to that with hepatic perfusion. Hepatic clearance of thiopental as the product of hepatic extraction of thiopental (with a median value of 0.29) and hepatic plasma flow was 0.21 l/min. CONCLUSIONS. Thiopental is subject to a relatively low hepatic extraction of 0.29. Thus, changes in hepatic perfusion do not influence the elimination of thiopental. The actions of thiopental on global hemodynamics are comparable with the results found in the literature, characterized by a significant reduction in MAP and cardiac output after induction. The hepatic clearance of thiopental found in this study, with an absolute value of 0.21 l/min, is absolutely comparable with the data for total-body clearance reported in the literature. It is concluded that the liver is the only organ responsible for the elimination of thiopental in humans.
Lange
H
H
Zentrum Anästhesiologie, Rettungs- und Intensivmedizin, Universitätsklinik Göttingen.
Stephan
H
H
Zielmann
S
S
Brandt
C
C
Sonntag
H
H
D000328:Adult; D001026:Coronary Artery Bypass; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013874:Thiopental / Q000097:blood / Q000493:pharmacokinetics*
D013874:Thiopental
Hepatische Elimination von Thiopental bei koronarchirurgischen Patienten.