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Background: To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4 degrees C using a standard preservation-reperfusion sequence., Methods: Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4 degrees C, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30-min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37 degrees C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady-state., Results: After warming to 37 degrees C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37 degrees C (< 16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group., Conclusions: Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.

Background: Mivacurium's rapid onset and short duration of action in children suggests that intramuscular administration might treat laryngospasm and facilitate tracheal intubation without producing prolonged paralysis. Accordingly, the authors measured the neuromuscular effects of intramuscular mivacurium in anesthetized infants and children., Methods: Twenty unpremedicated infants and children (3 months to 5 yr of age) were anesthetized with nitrous oxide and halothane and permitted to breathe spontaneously. When anesthetic conditions were stable, mivacurium was injected into the quadriceps or deltoid muscle. Minute ventilation and adductor pollicis twitch tension were measured. The initial mivacurium dose was 250 micrograms/kg and was increased (to a maximum of 800 micrograms/kg, at which dose the trial was ended) or decreased according to the response of the previous patient, the goal being to bracket the dose producing 80-90% twitch depression within 5 min of drug administration., Results: No patient achieved > 80% twitch depression within 5 min of mivacurium administration. Peak twitch depression was 90 +/- 13% (mean +/- SD) for infants and 88 +/- 15% for children at 15.0 +/- 4.6 min and 18.4 +/- 6.4 min, respectively. Ventilatory depression (a 50% decrease in minute ventilation or a 10-mmHg increase in end-tidal carbon dioxide tension) occurred at 9.0 +/- 4.4 min in nine infants and 13.6 +/- 7.5 min in 10 children; ventilatory depression did not develop in one infant given a dose of 350 micrograms/kg. Time to peak twitch depression or ventilatory depression was not faster with larger doses., Conclusions: Although ventilatory depression preceded twitch depression, both occurred later with intramuscular mivacurium than would be expected after intravenous mivacurium or intramuscular succinylcholine. The authors speculate that the onset of intramuscular mivacurium is too slow to treat laryngospasm or to facilitate routine tracheal intubation in infants or children, despite administration of large doses.