Differential effects of anesthetics on endotoxin-induced liver injury

J Trauma. 2005 Apr;58(4):711-6; discussion 716-7. doi: 10.1097/01.ta.0000159245.60495.00.


Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Upregulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1.

Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot.

Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS.

Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics / pharmacology*
  • Animals
  • Female
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Isoflurane / pharmacology*
  • Ketamine / pharmacology*
  • Lipopolysaccharides
  • Liver / drug effects*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / metabolism*


  • Anesthetics
  • Lipopolysaccharides
  • Ketamine
  • Isoflurane
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1