Pharmacodynamic Changes of Atracurium during Induced Liver Cirrhosis Using Carbon Tetrachloride Intoxication in Rabbits

Kim, Kyo Sang; Jang, Ho Sun; Cheong, Mi Ae; Shim, Jae Chol; Kim, Kyoung Hun

Abstract

BACKGROUND: Atracurium appears to be a neuromuscular blocking agent best suited for use in patients with renal failure. The influence on the neuromuscular effect of atracurium has been studied in rabbits with experimental liver cirrhosis induced by subcutaneous injection of carbon tetrachloride (CCl4).
METHODS
Cirrhosis was induced in rabbits by CCl4 treatment for 11 weeks. Rabbits were randomly assigned to two groups; control group: corn oil 0.5 ml/kg/2 days sq for 11 weeks; study group: CCl4 0.5 ml/kg/2 days mixed 1 : 1 with corn oil sq for 11 weeks. The dose-response relations of atracurium were studied in sixteen rabbits during thiopental anesthesia. They received atracurium 60, 80 and 100microgram/kg in control group, and 80, 100 and 120microgram/kg in study group, respectively. The time course of atracurium 0.2 mg/kg in sixteen rabbits was evaluated in each groups. Three fragments of each liver lobe at the end of the experimental period were collected and processed for light microscopy, and performed the histological examination.
RESULTS
After eleven-week CCl4 treatment, liver histology demonstrated well-defined liver cirrhosis, and increased AST and ALT compared with controls. The calculated ED50 for atracurium were 81.9+/-6.8microgram/kg and 101.1+/-9.4microgram/kg, respectively, in control and study group, and corresponding ED95 was 124.8+/-9.7microgram/kg and 156.1+/-12.1microgram/kg, respectively. There were significant difference between two groups (P < 0.001). The times after atracurium until 95% twitch recovery in control and study group were 31.7+/-6.7 min and 32.8+/-7.4 min, respectively. There were no difference between two groups.
CONCLUSIONS
Atracurium in the experimental liver cirrhosis model induced by CCl4 has a decreased potency, but a similar duration of action compared with control. It is suggested that atracurium was also used with monitoring of neuromuscular function in patients with hepatic dysfunction.