ATRACURIUM INFUSIONS IN PATIENTS WITH FULMINANT HEPATIC-FAILURE AWAITING LIVER-TRANSPLANTATION

Objective: To determine the pharmacokinetics and pharmacodynamics of t he neuromuscular blocking agent atracurium besylate in patients with f ulminant hepatic failure (FHF). Design: Open study of patients receivi ng atracurium infusions to facilitate mechanical ventilation. Setting: Intensive care unit in a tertiary referral university teaching hospit al. Patients: Ten encephalopathic patients with FHF requiring mechanic al ventilation while awaiting orthotopic liver transplantation. Three patients died before transplantation could be performed, three died af ter transplantation, and four survived following successful transplant ation. Methods: Plasma, urine and dialysate fluid were analysed for at racurium and its metabolites using HPLC. Neuromuscular blockade was me asured using transcutaneous ulnar nerve stimulation and an acceleromet er. Electroencephalography and liver function tests were performed dai ly. Results: Patients received atracurium infusions for a period rangi ng from 38 to 217 h. Six patients required continuous arteriovenous ha emodiafiltration (CAVHD) to replace renal function. Atracurium mean st eady state clearance was 8.6 ml/min/kg, and train-of-four recovery rat io to 75% took 63 min (range 32-108). Laudanosine clearance was marked ly reduced in the non-survivors; the half-life was 38.5 hrs compared w ith 5.3 h in the 4 patients who underwent successful transplantation. Laudanosine accumulation could be observed in all patients before tran splantation, but kinetics returned to normal after successful transpla ntation. The highest laudanosine level recorded was 6,860 ng/ml. There was no evidence of adverse central neurological effects attributable to laudanosine. CAVHD did not contribute significantly to clearance of atracurium or its metabolites. Conclusions: Atracurium kinetics and d ynamics are near-normal even in patients with fulminant hepatic failur e and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantat ion of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appr opriate choice for producing neuromuscular blockade for periods of sev eral days in patients with fulminant hepatic failure and renal impairm ent.