Plasma concentrations of laudanosine, but not of atracurium, are increased during the anhepatic phase of orthotopic liver transplantation in pigs

• Published in: Anesthesiology (Philadelphia) Vol. 72; no. 1; pp. 145 - 152
• Main Authors: PITTET, J.-F, TASSONYI, E, SCHOPFER, C, MOREL, D. R, MENTHA, G, FATHI, M, LE COULTRE, C, STEINIG, D. A, BENAKIS, A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 1990
• Subjects: Anesthetics. Neuromuscular blocking agents; Animals; Atracurium - blood; Atracurium - metabolism; Atracurium - pharmacokinetics; Biological and medical sciences; Isoquinolines - blood; Liver - physiology; Liver Transplantation - physiology; Medical sciences; Neuropharmacology; Norepinephrine - blood; Pharmacology. Drug treatments; Swine; Intravenous administration; Metabolite; Liver; Single dose; Hepatic disease; Transplantation; Catecholamine; Metabolism; Pig; Neuromuscular blocking agent; Liver function; Vertebrata; Mammalia; Bolus injection; Animal; Neurotransmitter; Norepinephrine; Artiodactyla; Pharmacokinetics; Ungulata; Sympathic nervous system
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199001000-00024

To quantify the changes in plasma concentrations of atracurium and laudanosine induced by the lack of hepatic function and circulation, the authors studied nine domestic pigs (22-25 kg) undergoing an orthotopic liver transplantation, and three control animals without surgery, using atracurium as the muscle relaxant. After intubation facilitated by isoflurane 2-3%, anesthesia was maintained with isoflurane (0.5% in oxygen) and fentanyl (4 micrograms.kg-1.hr-1). Ventilation was controlled to keep end-tidal CO2 at 35-40 mmHg, body temperature maintained at 35.5-37.5 degrees C, and arterial pH at 7.35-7.50. The right sciatic nerve was stimulated with a nerve stimulator delivering a single twitch at 0.1 Hz with 0.2-ms duration, at supramaximal stimulation. The force of the corresponding evoked isometric muscle contraction was continuously measured by a force-displacement transducer. A single iv bolus of atracurium (2 mg/kg) was given to obtain a 90-95% twitch depression, followed 5 min later by a constant-rate iv infusion of atracurium at 120 micrograms.kg-1.min-1 maintained during the entire investigation. Blood samples for plasma atracurium and laudanosine concentrations were drawn every 15 min. In the control group, plasma concentrations of atracurium remained stable between 6.5-8.0 micrograms/ml following initial bolus injection; plasma concentrations of laudanosine increased during the first 60 min, then remained stable between 0.69-0.74 micrograms/ml up to the end of the study. In animals undergoing transplantation, plasma concentrations of atracurium remained stable between 10-12 micrograms/ml, despite a 90-min duration of liver exclusion.