Do the lungs contribute to propofol elimination in patients during orthotopic liver transplantation without veno-venous bypass?

BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol. METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate of 2 mg x kg-1 x h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the first hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed-phase, high-performance liquid chromatographic method with fluorescence detection. RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose significantly compared with T0 and T1 (P<0.01) respectively. After reperfusion, the drug concentrations at T4, T5 and T6 decreased significantly compared with T2, T3 (P<0.01) respectively. There were no significant differences in plasma propofol concentrations between the pulmonary and radial arteries at any time points. CONCLUSIONS: Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans.

OBJECTIVE: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. METHODS: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. RESULTS: Rocuronium requirement, which were (0.468+/-0.167) mg/(kg.h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303+/-0.134) mg/(kg.h) and returned to the initial values at the neohepatic period ((0.429+/-0.130) mg/(kg.h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. CONCLUSIONS: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.