Influence of incubated atracurium on rat liver function

Degradation of atracurium by Hofmann elimination and ester hydrolysis depends mainly on pH and temperature and is said to be independent of liver and kidney function. Consequently atracurium is used widely in patients with liver failure. However, there is evidence that incubation of atracurium at 37 degrees C and pH 8 leads to leakage of LDH from hepatocyte cell cultures. We have tested the hepatotoxic effects of incubated atracurium in an isolated perfused rat liver model. After equilibration, atracurium 2010 mumol ml-1 (preincubated at pH 8 and 37 degrees C for 120 min) was administered over a period of 10 min followed by perfusion of Krebs-Henseleit bicarbonate buffer for 60 min. We found that incubation resulted in considerable degradation of atracurium and formation of laudanosine. Administration of incubated atracurium did not produce either biochemical or morphological damage to liver cells, but caused considerable increase in bile flow. We conclude that administration of preincubated atracurium did not produce impairment of liver cell function. The increase in bile flow could be beneficial if it occurs clinically.