ED50 and Recovery Times After Propofol in Rats with Graded Cirrhosis

Abstract

Patients with end-stage liver disease have increased sensitivity to general anesthetics. In this study, we sought to quantify sensitivity to propofol as a function of the degree of liver disease, in a rat model of cirrhosis. Liver disease was induced by carbon tetrachloride (CCl(4)) injections for 6, 9, or 12 weeks in 3 study groups. Control rats received saline injections on the same schedule as CCl(4)-injected rats. A second control (comparison) group was treated with phenobarbital for a week followed by 9 weeks of phenobarbital and 10% ethanol in drinking water. Liver function was assessed by liver function tests and pathologic scoring of liver histology. Progressively worse cirrhosis was associated with longer CCl(4) treatment by histologic criteria, by hypersplenism, liver to body weight ratios, and liver function tests. The major findings were that mild liver disease (either steatosis or fibrosis) was not associated with increased propofol sensitivity, but recovery times after propofol bolus and propofol infusion were significantly increased in rats with more severe liver fibrosis. Propofol sensitivity is not significantly affected in the setting of mild liver disease, similar to clinical observations, but end-stage liver disease (fibrosis) is associated with significantly prolonged time to recovery after propofol infusion. The progressive liver disease model used in these studies is useful for rigorously studying anesthetic sensitivity as a function of degree of hepatocellular-fibrotic liver disease.