Plasma Laudanosine Levels in Patients Given Atracurium During Liver Transplantation

Abstract

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.

Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure

“…infusion was commenced in the other arm for 51W89 administration. A bolus dose of 51W89 0.1 mg kg 91 (2 ED95 [10,11]) was then given into the infusion over 10 s. Additional blood samples were obtained at 2,4,6,8,10,12,15,20,25,30,45,60, 90, 120, 240 and 480 min. After preliminary results were available from the first 12 patients, an additional sample was obtained at 150 min (this included the last eight healthy patients and the last 13 renal failure patients).…”

Identification and Quantitation of Six Non-Depolarizing Neuromuscular Blocking Agents by LC-MS in Biological Fluids

“…With such doses, respiratory assistance is necessary. Clinical studies (15,16) have reported that the plasma concentration of iaudanosine was usually less than 0.5 mg/L. Moreover, if cisatracufium is used, the plasma concentrations of laudanosine are even lower.…”

Transplante hepático

“…A laudanosina atravessa a barreira hematoencefálica e pode ser encontrada no líquido céfalo-raquidiano com elevado potencial de neurotoxicidade (Lawhead et al, 1993).…”

“…As concentrações plasmáticas do atracúrio permanecem constantes durante as fases pré-anepática e anepática, mas diminuem no final da fase neo-hepáitca, visto que as concentrações da laudanosina aumentam em cada fase (Lawhead et al, 1993). Consequentemente, o acumulo da laudanosina foi observado nos pacientes com hepatite fulminante que aguardavam o TOF e receberam infusão contínua de atracúrio para facilitar a ventilação mecânica dos pulmões.…”