No abstract

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.

The effect of indomethacin on protein degradation in skeletal muscle from septic rats was investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. Protein degradation rate was estimated by measuring release of tyrosine from incubated soleus (SOL) and extensor digitorum longus (EDL) muscles. Three experiments were performed. In the first experiment, indomethacin was administered subcutaneously (3 mg/kg) at the time of CLP and again after 3 hours. Control rats received corresponding volumes of solvent. Groups of rats were studied after 8 hours (early sepsis) or 16 hours (late sepsis). In the second experiment, the animals were pretreated 45 minutes before induction of sepsis with indomethacin (3 mg/kg) and again 3 hours after CLP and were studied during early sepsis. In the third experiment, indomethacin was added in vitro (3 microM) to incubated normal or septic muscle or to normal muscle incubated in the presence of plasma from septic animals, and release of prostaglandin E2 (PGE2) by incubated muscle was measured in addition to protein degradation. There was no mortality in early sepsis. Survival rate 16 hours after CLP was 8/16 (50%) in rats receiving control injections and 7/15 (47%) in indomethacin-treated rats (NS). Proteolytic rate in incubated EDL and SOL was increased by 20-25% during early sepsis and by 30-50% during late sepsis. The increased proteolytic rate was not affected by administration of indomethacin, neither in the first nor in the second experiment. When indomethacin was added in vitro, release of PGE2 by septic muscles and by normal muscles incubated in the presence of septic plasma was reduced by about 50%, but the increased proteolytic rate in these muscles was not affected. In normal muscle, neither release of PGE2 nor protein degradation was affected by indomethacin in vitro. The present results do not support a role for prostaglandins in the enhancement of muscle proteolysis during sepsis. Since neither survival rate nor protein breakdown was affected by indomethacin, recent suggestions to use this substance in the treatment of septic patients might be questioned.