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Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group and 47% in the acute hepatitis group. Encephalopathy appeared to correlate with individual amino acids differentially in the various groups and with the ratio between the aromatic and the branched-chain amino acids. Ammonia did not correlate with either the degree of encephalopathy or improvement therefrom. In 24 Patients therapy for hepatic encephalopathy was limited to infusion of the branched-chain enriched amino acid solution only, with wake-up in 66% of this group. The results strongly suggest that in protein intolerant patients requiring nutritional support, infusion with branchedchain enriched amino acid solutions is well tolerated with either no worsening of or improvement in hepatic encephalopathy coincident with the achievement of nitrogen equilibrium and adequate nutritional support.

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Two experiments were conducted to estimate total non-protein energy and nitrogen requirements in growing healthy male Wistar rats nourished by parenteral nutrition. In experiment 1, non-protein energy varying from 30 to 70 kcal/day/rat were administered to animals receiving a constant dose of 80 mg nitrogen, plus vitamins and minerals. In experiment 2, nitrogen dosages varying from 0 to 280 mg N/day/rat with a constant dose of 60 kcal non-protein energy were studied. The formulation of the amino acid solution used in both experiments was based upon recommended oral amino acid requirements for growing rats. Dextrose served as the source of non-protein energy. Weight gain and nitrogen balance during a 6-day experimental period were used to determine requirements. Plasma free amino acids were also analyzed to evaluate the amino acid solution. Results indicate that under total parenteral nutrition conditions 578 to 621 mg/kg body weight3/4 nitrogen and 171 to 182 kcal/kg body weight3/4 non-protein energy are required to achieve growth of approximately 3 g/day. Inconsistent responses of plasma amino acid concentrations to the amounts infused were observed. It is suggested that the determined requirements can be applied as guidelines to research using the rat as an animal model in total parenteral nutrition.