Burgmann H, Reckendorfer H, Sperlich M, Tüchy G L, Spieckermann P G, Weindlmayr-Göttel M, Schwarz S
Department of Infectious Diseases, University of Vienna, Austria.
Br J Anaesth. 1994 Mar;72(3):324-7. doi: 10.1093/bja/72.3.324.
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.
阿曲库铵通过霍夫曼消除反应和酯水解作用发生降解，这主要取决于pH值和温度，且据说与肝肾功能无关。因此，阿曲库铵广泛用于肝功能衰竭患者。然而，有证据表明，在37℃和pH值为8的条件下孵育阿曲库铵会导致肝细胞培养物中乳酸脱氢酶泄漏。我们在离体灌注大鼠肝脏模型中测试了孵育后的阿曲库铵的肝毒性作用。平衡后，在10分钟内给予2010μmol/ml的阿曲库铵（在pH值为8和37℃下预孵育120分钟），随后用krebs-Henseleit碳酸氢盐缓冲液灌注60分钟。我们发现孵育导致阿曲库铵大量降解并生成劳丹诺辛。给予孵育后的阿曲库铵对肝细胞既未造成生化损伤也未造成形态损伤，但导致胆汁流量显著增加。我们得出结论，给予预孵育的阿曲库铵不会导致肝细胞功能受损。如果临床上出现胆汁流量增加，可能会有益处。
