title: ED50 and recovery times after propofol in rats with graded cirrhosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Anesthesiology, General Hospital of Ning Xia Medical University, Yin Chuan, China.
authors: Zhenzhou
authors: Z
authors: Li
authors: Xuexin
authors: X
authors: Chen
authors: Jinhai
authors: J
authors: Meng
authors: Liqin
authors: L
authors: Deng
authors: Hanxiang
authors: H
authors: Ma
authors: Marie
authors: M
authors: Csete
authors: Lize
authors: L
authors: Xiong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D018450:Disease Progression; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D015415:Biomarkers; D012709:Serum Albumin; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015742:Propofol