Metabolic effect of short-term total parenteral nutrition highly enriched with leucine or valine in rats recovering from severe trauma.

The metabolic impact of infusing a large amount of leucine (Leu) or valine (Val) was examined with regard to the corrective effect of total parenteral nutrition (TPN). Rats recovering from severe sepsis received either Leu- or Val-enriched TPN solution for 30 hours. The in vivo behavior of the amino acids administered was explored by a pulse injection of 14C-labeled Leu or Val. The recovery of 14CO2 from Leu increased by 64% in the septic rats of Leu-TPN group (41% of dose; p less than .01), as compared with control rats receiving the same TPN solution, whereas no significant rise in the 14CO2 recovery from Val occurred in the septic rats given Val-TPN (45% of dose) in comparison with the corresponding controls. The enhancement of Leu catabolism to CO2 in the Leu-TPN group was compatible with the alterations of urinary nitrogen excretion, plasma Leu level, and metabolite contents of liver and muscle. The only difference in metabolite levels observed between the two TPN groups was in hepatic total adenine nucleotides. Plasma amino acid levels were largely unaffected by infusion of these TPN solutions highly enriched with branched-chain amino acids (45%), except for an approximately threefold elevation of the Val level in Val-TPN rats. Thus, when administered in a large quantity during such short-term TPN, Leu can exert its metabolic effect without causing an imbalance in plasma amino acids under severe catabolic conditions.     

Calciuria in total parenteral nutrition: effects of amino acids and glucose in rats

Total parenteral nutrition (TPN) is known to cause hypercalciuria and negative calcium balance in some patients. We have now shown that the administration of TPN to rats causes marked increases in urinary calcium losses. Moreover, urinary calcium excretion in the TPN rat responds to changes in the infusate concentration of calcium and amino acids similarly to what has been observed in TPN patients. For any given increase in the amount of calcium infused 130% more calcium was excreted in the urine by rats receiving TPN compared to rats receiving saline alone. At a fixed level of calcium infused, urinary calcium increased linearly when the amino acid content of the infusate was increased from 0 to 2.75 to 4.25%. However, a reduction in the glucose load, via isocaloric substitution with lipid by 60%, had no effect on urinary calcium excretion. The TPN rat appears to be a promising animal model in which to investigate the hypercalciuretic effect of intravenous nutrition, particularly as calcium homeostasis may be affected by various nutritional components of the TPN solution.     

Response of glutamine metabolism to glutamine-supplemented parenteral nutrition

BACKGROUND: Increasing evidence suggests that glutamine is important for the function of many organ systems and supports the use of glutamine-enriched total parenteral nutrition (TPN) during severe illness. However, the effect of prolonged glutamine supplementation on glutamine kinetics has not been studied. OBJECTIVE: We investigated the effect of 8-10 d of TPN enriched with glutamine dipeptides on glutamine kinetics. DESIGN: Twenty-three preoperative patients were randomly allocated to receive either TPN enriched with glutamine dipeptides (60 micromol glutamine*kg body wt(-1)*h(-1)) or isonitrogenous, isoenergetic, glutamine-free TPN. A primed, continuous, 6-h intravenous infusion of L-[5-(15)N]glutamine and L-[1-(13)C]leucine was given before (baseline) and 8-10 d after the TPN solutions were administered. Baseline measurements were performed after a 40-h administration of a standard solution of glucose and amino acids (no glutamine). RESULTS: Glutamine-enriched TPN increased the total appearance rate of glutamine (P: < 0.05) but did not inhibit or increase the endogenous appearance rate. The standard TPN solution also increased the glutamine appearance rate (P: < 0.05), but the change was much smaller than in the glutamine-supplemented group (P: < 0.01). The plasma glutamine concentration did not rise significantly during either treatment, suggesting increased tissue glutamine utilization, especially in the glutamine-supplemented group. CONCLUSION: In view of the enhanced glutamine requirements in response to trauma and disease by tissues such as those of the gut, the immune system, and the liver, increased glutamine availability during glutamine-enriched TPN may be beneficial preoperatively in patients with gastrointestinal disease.     

Changes in muscle and plasma amino acid metabolism in severe malnutrition--the influence of total parenteral nutrition

The concentrations of free amino acids in muscle and plasma were determined in nine female patients with severe anorexia nervosa before and after 3 to 5 weeks of total parenteral nutrition (TPN). The patients had lost 25 to 42% of their pre-morbid weight. During TPN their weight gain was around 2.5 kg/week. Initially total non-essential amino acids (NEAA) in muscle were decreased 30% compared to controls. The major part of this depletion was due to a 40% reduction in glutamine. After TPN the level of glutamine normalized. Alanine, being normal before TPN, decreased after TPN. Proline and several other non-essential amino acids in muscle were decreased before and after TPN. Total essential amino acids (EAA) in muscle were initially normal and were not significantly affected by TPN. Total NEAA in plasma were decreased at admission and normalized after TPN. Total EAA in plasma, however, were normal both before and after TPN. This study demonstrates that severely malnourished patients with anorexia nervosa have changes in amino acid patterns in both muscle and plasma. These changes were largely, though not completely, reversed after 3 to 5 weeks of TPN.     

Studies on the toxicity and efficacy of a new amino acid solution in pediatric parenteral nutrition

The optimum composition and concentration of crystalline amino acid solutions necessary for growth and brain maturation in critically ill infants requiring total parenteral nutrition (TPN) are unknown. Either an excess or a deficiency of amino acids could theoretically impair normal brain development in the neonate. The purpose of this study was to compare the toxicity and efficacy of two intravenous amino acid solutions, Neopham, modeled after the amino acid pattern found in human breast milk, and Aminosyn, a marketed product, designed for general usage. Sixteen infants and children requiring continuous intravenous nutrition for at least 7 days received the Neopham amino acid solution, and eight infants and children received the Aminosyn amino acid solution as part of a total parenteral nutrition regimen which included glucose, the fat emulsion Intralipid, as well as routine mineral and vitamin additives. There were no significant differences in mean gestational age, body weight, postnatal age, or mean daily nutrient intake between the patients receiving Aminosyn or Neopham. The daily nitrogen intake, excretion, and retention were similar in both groups. In addition, there were no statistically significant differences in either hematological or biochemical parameters between the two study groups. The plasma levels of three essential amino acids, isoleucine, methionine, and valine, rose significantly higher in the Aminosyn-treated patients. The plasma levels of all the essential amino acids increased in both study groups.     

Apparent nitrogen balance and 3-methylhistidine urinary excretion in intravenously fed children with trauma and infection

This study was designed to compare and evaluate the effects of two isocaloric parenteral nutrition infusions, FreAmine and F080, differing in their amino acid composition, on the apparent nitrogen balance and urinary excretion of 3-methylhistidine in children with trauma (n = 27) or grave infection (n = 24). Trauma patients at the beginning of parenteral nutrition showed a more negative nitrogen balance than infected children, but in all children the apparent nitrogen balance increased to become positive and the 3-methylhistidine urinary excretion dropped. No differences related to the amino acid composition of the parenteral nutrition solutions were found. Apparent nitrogen balance and 3-methylhistidine excretion were correlated in all study groups irrespective of urine sample time. The enriched branched chain amino acid solution used for parenteral nutrition of trauma and infected children did not show a better effect than the non-enriched one in terms of muscle catabolism and nitrogen balance. The use of adequate nutritional support including both amino acids and energy source is of major importance in children recovering from trauma and infection.     

Urinary copper losses in infants receiving free amino acid solutions

Plasma amino acids and the 24-h urinary excretion of copper and amino acids were measured in 18 infants receiving 0.4 g N/kg/day as free amino acids as part of a total parenteral nutrition regimen. Urinary copper excretion correlated positively with total excretion of alpha-amino nitrogen, in general, and the excretion of glycine, methionine, histidine, and lysine, in particular. Infants who received FreAmine II as compared to FreAmine III generally had increased plasma concentrations of glycine and methionine and increased urinary excretion of total alpha-amino nitrogen, glycine, methionine, and of copper. Chronic losses of copper in the urine of infants receiving free amino acid solutions may contribute to copper depletion and the development of a copper deficiency syndrome.     

The effect of L-carnitine-supplemented total parenteral nutrition on tissue amino acid concentrations in piglets

Miniature piglets underwent total parenteral nutrition (TPN) with and without L-carnitine supplementation during a 7-day period. Thereafter the tissue amino acid concentrations of liver, heart, skeletal muscle and brain were determined and compared to those of orally fed animals. The altered tissue amino acid concentrations during TPN without carnitine returned to normal when L-carnitine was supplemented. The most striking changes of tissue concentrations showed taurine in liver, muscle and brain and ethanolamine in heart and brain. In muscle the branched-chain amino acids were increased when L-carnitine was added to the TPN regime. Ethanolamine changes were discussed with respect to the position of this amino acid in the synthesis of phospholipids. The marked decrease of brain taurine concentrations after carnitine-free TPN was accompanied by reduced values for GABA. Both the substances function as inhibitory transmitters in the brain and should be considered when seizure activity in patients with systemic carnitine deficiency is discussed.     

Parenteral nutrition of injured patients: Effect of manipulation of aminoacid infusion (increasing branched chain while decreasing aromatic and sulphurated aminoacids)

Sixteen critically ill injured patients received parenteral nutrition providing nitrogen (0.34 g kg(-1) day(-1)) and glucose (32 kcal kg(-1) day(-1)) for 5 days. They were randomly divided into two groups with respect to aminoacid supply: an essential aminoacid solution vs the same solution enriched in branched chain amino acid (BCAA) content and decreased in phenylalanine and methionine content (mean BCAA intake, 0.55 vs 0.69 g kg(-1) day(-1)). Basal values of nitrogen metabolism without treatment showed no difference between the two groups. Nitrogen losses and 3 methylhistidine (3-MEH) excretion were elevated; the plasma aminoacid pattern was altered by the trauma and except for phenylalanine, aspartate and glutamate, plasma aminoacid concentrations were decreased below normal values. Net muscular aminoacid output was demonstrated by femoral arterio-venous (av) differences that were all negative except for glutamate and citrulline TPN with both solutions improved the nitrogen balance and reduced the negative aminoacid balance across the leg. Adjusting a TPN regimen to increase the BCAA content without altering the total nitrogen infused, had no effect on overall nitrogen balance, but exerted a beneficial effect on body protein catabolism, as assessed by the urinary 3-MEH excretion rate, and a transient improvement in the aminoacid balance across the leg at the peak of the infusion. The short-lived effect of BCAA suggest a metabolic effect of these aminoacids which deserves further study.     

Proline supplementation to parenteral nutrition results in greater rates of protein synthesis in the muscle, skin, and small intestine in neonatal Yucatan miniature piglets

Proline and arginine are each indispensable during parenteral feeding due to limited interconversion by an atrophied gut. Commercial amino acid parenteral products designed for neonates contain proline concentrations that differ by almost 4-fold. To assess the adequacy of the lowest concentration of proline provided in commercial total parenteral nutrition (TPN) products, we compared rates of tissue-specific protein synthesis and nitrogen balance in neonatal piglets provided TPN at 2 different proline concentrations. Yucatan miniature piglets (9-11 d old, n = 12) were randomized to complete isonitrogenous TPN diets with low proline (LP; L-proline as 3% of amino acids) or proline supplemented (PS; 9%). After 7 d of receiving TPN, rates of protein synthesis in liver, gastrocnemius muscle, jejunal mucosa, and skin were determined by the flooding dose technique and tissue free amino acids were measured. Nitrogen balance was assessed during the last 3 d. The LP TPN resulted in lower free proline concentrations in plasma, muscle, and skin (P < 0.05) and lower rates of protein synthesis in the jejunum (by 25%; P = 0.02), muscle (by 45%; P = 0.015), and skin (by 60%; P = 0.01); there was no difference in liver. Nitrogen retention was 20% lower in the LP group (P = 0.01). In conclusion, muscle and skin protein synthesis was profoundly sensitive to parenteral proline supply and the reduced protein synthesis in the intestine could affect intestinal integrity. Low-proline TPN solutions that are currently in wide use in neonatal care may result in impaired tissue growth.     

Effects of artificial nutrition on the nutritional status of cancer patients

The paper critically analyzes available data on the nutritional and metabolic effects of total parenteral nutrition (TPN) and enteral nutrition (EN) in cachectic cancer patients. Only papers dealing with adult cancer patients and providing data regarding type of tumor, duration of the nutritional support, and administration rate of calories and amino acids, validated by statistical analysis of the results, are included. The main conclusions are the following: (1) No nutritional variable worsened in cancer patients receiving TPN or EN, in conditions in which progressive deterioration of the nutritional status is the rule. (2) The nutritional variables improved by TPN and EN were body weight, fat mass, and some indicators of lean body mass (nitrogen balance and whole body potassium). Thyroxin-binding prealbumin and retinol-binding protein increased only with TPN, whereas some immunologic indexes (complement factors and lymphocytes) improved only with EN. (3) The daily regimens which improved lean body mass and visceral proteins ranged from 35 to 55 kcal/kg and from 1.2 to 2.0 g of amino acids/kg for TPN; for EN it was 35 kcal/kg and 1.3 g of amino acids/kg. However, the enteral regimen capable of improving some immune responses included at least 42 kcal/kg and 2.3 g of amino acids/kg. (4) Only three randomized studies were performed to compare TPN and EN, and conflicting results were obtained. Only TPN showed some significant advantages with regard to weight gain, nitrogen balance, maintenance of serum albumin levels and some mineral balances. However, the advantage of TPN was not clear enough to recommend its indiscriminate use. The choice between TPN and EN should always consider the functionality of the GI tract, the need for hospitalization to start a TPN regimen, and the higher cost of intravenous feeding. (5) When comparing TPN to a standard oral diet, the following variables improved with the nutritional support: body weight, nitrogen balance, 3-methylhistidine, urinary excretion, and serum levels of transferrin, cholinesterase, thyroxin-binding prealbumin, and retinol-binding protein. (6) When comparing TPN with glucose vs TPN with glucose-lipids, no major difference was found with regard to most nutritional variables. In conclusion, nutritional support alone probably has a small role in managing a limited number of advanced cancer patients dying primarily because of malnutrition or mainly suffering from nutritional deterioration. It can also have a "permissive" role in those patients potentially candidate to an oncologic treatment which cannot be delivered because of a poor nutritional status.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma amino acid concentration changes during total parental nutrition in critically ill patients

In 16 critically ill patients with full-blown stress reaction and without severe organ failure, we studied the kinetics of the arterial plasma amino acid (aa) profile during the first 48 h of total parenteral nutrition (TPN) in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions giving, with the same nitrogen load, different intakes of individual amino acids. We found four different responses to the administered amino acids. Some amino acids showed a different trend depending on the dose given. At lower doses a steady state was achieved sooner. Plasma levels of amino acids not supplied in the TPN were unaffected or decreased, achieving a steady state at various times during the study period. We conclude that, in critically ill patients, stable arterial plasma amino acid concentrations are obtained within 24 h of starting TPN. In such patients, valid studies of the effect of amino acid solutions may therefore be carried out over short periods of time, thereby minimizing errors due to a fluctuating and unstable clinical state.     

Amino acid intake and urinary zinc excretion in newborn infants receiving total parenteral nutrition

Zinc deficiency is well described in infants on total parenteral nutrition (TPN). Urinary Zn excretion is the major source of Zn loss in the parenterally fed infant; factors causing increased zincuria will predispose the infant to Zn deficiency and affect the recommended Zn intake dosage. Histidine, threonine, and lysine have been shown to bind Zn increasing its renal ultrafilterability. The effect of the infusion of high and low lysine (206 +/- 34 vs 158 +/- 38 mg.kg-1.d-1; means +/- SD), threonine (147 +/- 24 vs 113 +/- 27), and histidine (124 +/- 34 vs 85 +/- 15) on urinary Zn excretion were determined in 23 newborns on TPN who received similar Zn intakes (6.8 +/- 1.4 mumol.kg-1.d-1). After a 72-h adaptation period each infant had urine collected for two 24-h periods. Despite the significant difference in amino acid intakes, mean urinary Zn excretion was identical (1.58 +/- 0.73 vs 1.56 +/- 0.63 mumol.kg-1.d-1). Hyperzincuria, therefore, does not occur when amino acids are infused at rates appropriate for the safety and nutritional maintenance of neonates.     

Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids.

Sepsis is characterized by an increase in the plasma concentration of aromatic amino acids (AAAs) and those containing sulfur and a decrease in the branched-chain amino acids (BCAAs). We studied changes in the plasma aminogram of septic patients given different types of total parenteral nutrition (TPN), analyzing variations in accordance with the type of TPN used and the importance that the use of BCAA may have in these patients. We studied 80 patients with peritonitis divided into two groups of 40 patients each: group 1 was given a solution with 22.5% BCAA and group 2 a solution with 45% BCAA. High BCAA content caused an increase in the plasma concentrations of these amino acids and in the BCAA/AAA quotient and a decrease in AAAs. Plasma concentrations of leucine and valine reached high, potentially toxic levels at 15 days when solutions with high BCAA content were used. Glycine increased in group 1, which may be important because of its tendency to produce hyperammonemia. BCAAs are of unquestioned nutritional importance in view of the evidence of changes that take place in muscle protein catabolism and in plasma amino acids. In the phase of increased protein catabolism, we saw a plasma amino acid pattern in keeping with the existing metabolic situation. The need for BCAA diminishes when the hypercatabolic state disappears.     

Total parenteral nutrition in cancer patients

One hundred and twenty-one cancer patients received 134 courses of total parenteral nutrition (TPN); almost all were treated with chemotherapy and/or radiotherapy. The average weight loss prior to TPN was 6.7 kg and albumin 3.1 g%/patient; 25% glucose solution with 4.25 g% amino acids was used as a calorie and nitrogen source. The average weight gain was 2.6 kg for those who received TPN less than 2 wk and 4.5 kg if TPN was given for greater than 2 wk. Complications were low; 3% had proven TPN-related septicemia. Mild to moderate reversible metabolic complications were common, although severe complications were rare; no one died because of TPN. Our experience confirms the previous reports that TPN can be given safely to malnourished compromised cancer patients.     

A comparative study of the efficiency of intragastric and parenteral nutrition in man

Solutions intended for parenteral nutrition were infused at constant rates intravenously and intragastrically in five healthy volunteers. Whole body utilization of nutrients was measured by indirect calorimetry and determination of nitrogen excretion in relation to circulating levels of substrates. Energy balance and urinary nitrogen excretion were the same in all subjects irrespective of whether nutrition was given intravenously or intragastrically. Minor differences in circulating levels of glucagon, alpha-amino nitrogen, and triglycerides were observed but had no impact on the energy and nitrogen metabolism. The results show that whole-body utilization of calories is the same with parenteral and enteral nutrition as evaluated over short time periods from the start of infusion. This is probably also true for amino acids.     

Effect of a new amino acid solution on nutritional status and nitrogen metabolism in rats with chronic renal failure undergoing hyperalimentation

We studied the effects of the new amino acid solution MRX-III on the nutritional status and nitrogen metabolism of rats with chronic renal failure (CRF) in comparison with those of a general amino acid solution (MPR-F). The essential amino acids/non-essential amino acids ratio was 3.21 for MRX-III and 1.09 for MPR-F. Rats with CRF, induced by 7/8 renal ablation, were divided into 6 groups of 8 rats each receiving total parenteral nutrition (TPN) containing MRX-III or MPR-F at a non-protein calorie/nitrogen ratio (Cal/N) of 300, 600 or 900 for 7 d. The rats were infused with test solutions containing the same amounts of non-protein calories. The cumulative nitrogen balance, as a nutritional index, in the MRX-III group was significantly higher than that in the MPR-F group at the Cal/N of 600 or 900, and the plasma albumin level at the Cal/N of 300. The plasma transferrin levels at the Cal/N of 900 in the MRX-III groups were significantly higher than those in the corresponding MPR-F groups. At all Cal/N, the MRX-III groups showed low levels of blood urea nitrogen and urinary excretion of ammonia and urea nitrogen as compared with the MPR-F groups at the same Cal/N. The plasma amino acid concentration profiles in the MRX-III groups after TPN showed greater similarity to that in the Normal group as compared with the profiles in the corresponding MPR-F groups. No aggravation of renal failure was observed in any TPN groups during TPN. These results indicate that, in rats with CRF undergoing hyperalimentation, the effects of MRX-III on the nutritional status and nitrogen metabolism are superior to those of the general amino acid solution, MPR-F. It is suggested that MRX-III could safely provide adequate amounts of nitrogen during hyperalimentation.     

Effect of starvation and total parenteral nutrition on electrolyte homeostasis in normal man

Elemental balances, and skeletal muscle membrane potential (Em) and biopsy were utilized to evaluate electrolyte homeostasis and body composition in 11 healthy adult volunteers after 10 days of starvation. This controlled, acute malnutrition was followed by refeeding for 10 days with two different, commonly used, total parenteral nutrition (TPN) solutions. Six subjects were refed with crystalline amino acids and dextrose (dextrose group), while five subjects received amino acids, dextrose, and lipid (lipid group). During starvation, negative balances for potassium, phosphorous, magnesium, and nitrogen were observed in both groups. When compared to starvation, total parenteral nutrition produced statistically significant (p less than 0.05) equilibrium or positive electrolyte and nitrogen balances for both, the dextrose and lipid groups. During TPN, there was a significantly (p less than 0.001) positive chloride balance in the lipid group when compared to the dextrose group. At the conclusion of the 10-day period of TPN, there was a decrease (p less than 0.05) in skeletal muscle Em. This change, in concert with the electrolyte balance data obtained during parenteral repletion, lead us to postulate that restoration of lean tissue protein and cellular function does not occur at a rate which might be inferred from the positive nitrogen balance observed in this model. A persistent defect in cellular function which was evident after starvation, suggests that a brief period of TPN is insufficient to restore skeletal muscle integrity.     

Muscle protein degradation in severely malnourished patients with chronic obstructive pulmonary disease subject to short-term total parenteral nutrition.

Patients with chronic obstructive pulmonary disease (COPD) often lose weight and muscle mass with progression of the disease. Muscle protein degradation in patients with COPD has never been examined before and during hypercaloric feeding. Eight severely malnourished patients with COPD were examined at home consuming their usual intake, in the hospital after 3 days of a meat-free regular oral diet (period B), and during a hypercaloric (55 kcal/kg) high-lipid (55%) parenteral formula (total parenteral nutrition [TPN]). During period B, 8 well-nourished patients and 10 malnourished cancer patients were used as control groups. Measurements included plasma assays, leg blood flow, leg exchange (of 3-methylhistidine [3MeH], glucose, lactate, and oxygen) and urinary measures of 3MeH, creatinine, and nitrogen. During period B, net release of 3MeH across the leg in patients with COPD was similar to that in well-nourished control subjects and cachectic cancer patients. In COPD patients, there was only a transient decrease in leg exchange values of 3MeH with administration of TPN. COPD patients demonstrated a reduction (p less than .01) in urinary 3MeH excretion and an increase in nitrogen balance (p less than .01) with TPN compared with period B. The decrease in muscle protein degradation with administration of TPN accounts for about 50% of the increase in nitrogen retention in patients with COPD. These data suggest that in severely malnourished patients with COPD the weight loss is not dependent on increased rates of skeletal muscle protein degradation; nevertheless, degradation rates attenuate with a positive nitrogen balance during nutrition repletion.     

Metabolic effect of parenteral nutrition in dogs with obstructive jaundice.

To assess the effect of total parenteral nutrition (TPN) on macronutrient metabolism in obstructive jaundice.

Forty adult mongrel dogs were equally divided into four groups: group I (PO-control) received sham ligation of common bile duct (CBDL) and was fed dog chow and water ad libitum; group II (PO-CBDL) underwent CBDL and was fed dog chow; group III (TPN-control) received sham CBDL and TPN; and group IV (TPN-CBDL) underwent CBDL and received TPN. Blood chemistries, plasma amino acids and liver histologies were studied before (Day 1) and at the end (Day 14) of the experiment.

A significant elevation of bilirubin and alkaline phosphatase was observed in dogs with CBDL. Blood glucose was not changed significantly in any group. Significant increases in triglyceride and cholesterol were present in CBDL dogs. Significant differences in the concentrations of a few plasma amino acids, including an elevation of phenylalanine, were found in TPN dogs. A significant increase in aromatic amino acids (AAA) and a noticeable depression of the molar ratio of branched-chain amino acids (BCAA) to AAA was present in TPN-CBDL dogs, as was a significant increase in blood ammonia.

In the presence of obstructive jaundice, TPN does not significantly affect carbohydrate or lipid metabolism. However, a derangement in protein metabolism with the standard TPN solution in current use suggests that either a modification of amino acid composition or an increase in total energy to protein energy ratio in TPN solution may be necessary to obviate such a consequence.