Hepatic failure and coma after liver resection is reversed by manipulation of gut contents: the role of endotoxin.
Despite significant improvements in the surgical care of patients, hepatic failure after extensive liver resection continues to be associated with a high morbidity and death. We postulated that hepatic failure after liver resection was related to gut-derived endotoxemia. Rats were randomized to receive oral gavage twice daily with one of the following preparations: (1) 0.9% saline; (2) neomycin sulfate and cefazolin; (3) cholestyramine; (4) lactulose. After 7 days of gavage, animals underwent either a two-thirds partial hepatectomy or sham operation. At time 0 (preresection), 10, 20, and 30 hours after resection, aortic blood was obtained for determination of ammonia, glutamine, and endotoxin levels. In selected animals, portal vein or inferior caval blood was obtained simultaneously with the aortic sample to evaluate the glutamine and ammonia exchange across the intestine and hind limb. Germ-free rats also underwent a partial hepatectomy or sham operation, and blood was obtained for glutamine and ammonia exchange at 0 and 20 hours after resection. Hepatectomy in the saline-pretreated rats resulted in a sixfold increase in plasma glutamine, increased uptake of glutamine and release of ammonia by the gut, increased release of glutamine by the hind-limb, and a high mortality rate. Pretreatment with agents that altered gut contents reduced the endotoxemia, maintained normal glutamine and ammonia levels, and reduced the mortality rate. Germ-free rats had a similar response to that seen in treated animals. Altering the gut contents in this model reduced the level of endotoxemia, blunted the catabolic response, and enhanced survival.
van Leeuwen
P A
PA
Laboratory for Surgical Metabolism and Nutrition, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115.
Hong
R W
RW
Rounds
J D
JD
Rodrick
M L
ML
Wilmore
D
D
D000641:Ammonia / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002437:Cefazolin / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood*; D005766:Gastrointestinal Contents; D005973:Glutamine / Q000097:blood; D006498:Hepatectomy / Q000009:adverse effects*; D006501:Hepatic Encephalopathy / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007552:Isotonic Solutions; D007792:Lactulose / Q000494:pharmacology; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D004731:Endotoxins; D007552:Isotonic Solutions; D005973:Glutamine; D002792:Cholestyramine Resin; D012965:Sodium Chloride; D007792:Lactulose; D000641:Ammonia; D009355:Neomycin; D002437:Cefazolin