Pharmacokinetics of rocuronium during the three stages of liver transplantation

BACKGROUND: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function. METHODS: Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined. RESULTS: During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1) x min(-1) and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl. CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepatic period, apparently a result of prolonged graft warm ischemia. The authors' finding of preservation of hepatic drug elimination in the hepatic allograft is consistent with limited data for other drugs evaluated during anesthesia.     

Progress in Nanoengineered Microstructures for Tunable High‐Current,High‐Temperature Superconducting Wires

High critical current densities (J_c) in thick films of the Y₁Ba₂Cu₃O_7–δ (YBCO, T_c ≈ 92 K) superconductor directly depend upon the types of nanoscale defects and their densities within the films. A major challenge for developing a viable wire technology is to introduce nanoscale defect structures into the YBCO grains of the thick film suitable for flux pinning and the tailoring of the superconducting properties to specific, application‐dependent, temperature and magnetic field conditions. Concurrently, the YBCO film needs to be integrated into a macroscopically defect‐free conductor in which the grain‐to‐grain connectivity maintains levels of inter‐grain J_c that are comparable to the intra‐grain J_c. That is, high critical current (I_c) YBCO coated conductors must contain engineered inhomogeneities on the nanoscale, while being homogeneous on the macroscale. An analysis is presented of the advances in high‐performance YBCO coated‐conductors using chemical solution deposition (CSD) based on metal trifluoroacetates and the subsequent processing to nano‐engineer the microstructure for tuneable superconducting wires. Multi‐scale structural, chemical, and electrical investigations of the CSD film processes, thick film development, key microstructural features, and wire properties are presented. Prospects for further development of much higher I_c wires for large‐scale, commercial application are discussed within the context of these recent advances.