Plasma laudanosine levels in patients given atracurium during liver transplantation.

Atracurium, a nondepolarizing muscle relaxant, does not depend on the liver for clearance, but its principal metabolite, laudanosine, is eliminated primarily by the liver and is potentially neurotoxic. We measured atracurium and laudanosine levels in 15 adult patients during the three stages of liver transplantation to assess the effect of major impairment of liver function. Atracurium was given in a bolus dose of 0.5 mg/kg followed by continuous infusion at a rate adjusted to maintain 95-99% of total neuromuscular block, as judged by train of four response to facial nerve stimulation. Atracurium levels remained constant at 1.4-1.8 micrograms/mL during the 180-min preanhepatic and 75-min anhepatic stages but decreased to a mean of 1.0 microgram/mL by the end of the 180-min postanhepatic stage. In contrast, laudanosine levels increased during each stage, being 0.40 +/- 0.18, 0.50 +/- 0.22, and 0.43 +/- 0.16 micrograms/mL after the preanhepatic, anhepatic, and postanhepatic stages, respectively. The highest individual value recorded was 1.02 microgram/mL. We conclude that, despite increases in laudanosine levels during each stage of liver transplantation in patients receiving atracurium, those levels are only about one-tenth of the maximum values previously reported in humans.