Total Parenteral Nutrition Regimen Research Articles

The degradation of vitamin A exposed to ultraviolet radiation

The degradation of vitamin A palmitate exposed to UV light was studied. Radiance energy was measured using a U.V. radiation monitor. Degradation in aqueous solutions was non-exponential and could be described by a polynomial equation. Degradation rate was dependent to a small extent on the initial concentration of vitamin A. Results suggested that the non-exponential nature of the degradation curve might be due to the protective effect of degradation products. Breakdown of vitamin A was similar in glass and PVC containers, but degradation was significantly slower in amino acid infusions. The monitor could be used to measure UV radiance from sunlight. This information can be used to estimate the losses of vitamin A palmitate after addition to total parenteral nutrition regimes. The clinical significance of the tailing phenomenon of the degradation process are discussed.

Tumor and host carcass changes during total parenteral nutrition in an anorectic rat-tumor system.

The independent effects of total parenteral nutrition (TPN) on tumor growth and host carcass are important in designing effective nutritional support. In this study, a TPN regimen was used to keep substrate intake at normal levels during a 10-day period of tumor-induced anorexia and cachexia in rats transplanted with a sarcoma. Tumor mass was increased in TPN-supported animals compared to orally-fed controls. Tumor composition (water, fat, nitrogen) was similar in all tumors. Host carcass mass in tumor-bearing (TB) animals was increased by TPN as compared to orally-fed TB controls, but not to the same extent as in orally-fed or TPN-supported nontumor-bearing controls. Host carcass composition determinations demonstrated significantly increased fat content but no significant change in protein or water content in TB-TPN animals compared to orally-fed TB animals. This study demonstrates increased tumor growth and increased host carcass fat stores secondary to TPN.

Parenteral Nutrition in Preterm Infants

Thirty-three premature infants receiving parenteral nutrition during the first 5 days of life were divided into three groups. Infants in group I (n = 13) received no ventilatory therapy. Those in groups II (n = 10) and III (n = 10) were intubated and artificially ventilated because of hyaline membrane disease, apnea, or other illness. All infants received glucose, amino acids, fat emulsion, and electrolytes in their total parenteral nutrition regimen. Groups I and II were administered a transfer-adapted amino acid solution (Aminoplasmal paed 5%) for their protein supplementation, and group III, a so-called human milk-adapted solution (Aminovenös 6%). The three groups were compared with respect to amino acid blood level, amino acid excretion, and nitrogen balance. Taurine levels decreased significantly during parenteral nutrition in all three groups. The other amino acids, with a few exceptions, remained within acceptable range. Elevations of serine, proline, and methionine were found in group III after the third day. All three groups exhibited good nitrogen retention. Excretion of amino acids was only about 1%.

Parenteral Nutrition in Preterm Infants

SummaryThirty‐three premature infants receiving parenteral nutrition during the first 5 days of life were divided into three groups. Infants in group I (n = 13) received no ventilatory therapy. Those in groups II (n = 10) and III (n = 10) were intubated and artificially ventilated because of hyaline membrane disease, apnea, or other illness. All infants received glucose, amino acids, fat emulsion, and electrolytes in their total parenteral nutrition regimen. Groups I and II were administered a transfer‐adapted amino acid solution (Aminoplasmal paed 5%) for their protein supplementation, and group III, a so‐called human milk‐adapted solution (Aminovenos 6%). The three groups were compared with respect to amino acid blood level, amino acid excretion, and nitrogen balance. Taurine levels decreased significantly during parenteral nutrition in all three groups. The other amino acids, with a few exceptions, remained within acceptable range. Elevations of serine, proline, and methionine were found in group III after the third day. All three groups exhibited good nitrogen retention. Excretion of amino acids was only about 1%.

Pancreatitis and intravenous fat: An association in patients with inflammatory bowel disease

Since recently adding Intralipid (IL) to our standard total parenteral nutrition (TPN) regimen for children with inflammatory bowel (IBD) disease, two children undergoing major intestinal resections have developed acute pancreatitis in the early postoperative period. Herein, we present the clinical summaries of these two patients, discuss the multifactoral etiologies of acute pancreatitis, and review the role of emulsified fat solutions in TPN in children with IBD.

Urinary excretion of carnitine in multiply injured patients on different regimens of total parenteral nutrition

Carnitine derives from intake of preformed exogenous carnitine and synthesis from lysine and methionine, but is absent in parenteral fluids. Urinary excretions of carnitine and its derivatives was measured in 30 patients 2–8 days after severe multiple injuries and compared with controls. The patients received five different isocaloric parenteral nutritional regimens; group 1 glucose and fat, group 2 glucose, fat and amino acids, group 3 glucose and insulin, group 4 glucose and amino acids, and group 5 branched-chain amino acids. The mean total carnitine excretion in healthy men was 420 μ mol 24 h ± 57 (SEM), and in women 266 μ mol 24 h ± 29 , 41% of which was free carnitine. Mean excretion of total carnitine during days 2–8 after trauma for the five groups was: 900 ± 100, 1169 ± 112, 1251 ± 102, 1023 ± 117, and 668 ± 128 μ mol 24 h , being significantly higher in groups 1–4 than in healthy men. The free carnitine fraction in the patients was significantly higher than in controlled healthy subjects. Total carnitine excretion was unaffected by different nutritional regimens in the very first days. During days 6–8, group 5, receiving branched-chain amino acids had lower excretion of total carnitine (compared to groups 2–4) and free carnitine (compared to groups 3–4). Groups 3 and 4 excreted a higher percentage as free carnitine compared to the other groups. A significant correlation was found between total carnitine and net nitrogen losses during the whole observation period and between total carnitine and 3-methylhistidine during days 6–8 after trauma.

Serum vitamin level maintenance in cancer patients on total parenteral nutrition

The quantity of water and fat soluble vitamins required to maintain serum levels in cancer patients on total parenteral nutrition (TPN) has yet to be determined. A prospective evaluation of our current intravenous vitamin regimen during TPN was performed in order to define these requirements. Seventy-five patients receiving 97 TPN courses for seven to 60 days were studied. Serum levels of vitamins A (74 courses), B12 (85), folate (62), C (97), and 25-OH-cholecalciferol (25-OH-D) (9) were available for analysis. Daily vitamin intakes were recorded and serum levels were determined weekly. Restoration and maintenance of normal mean serum vitamin levels were achieved for all but 25-OH-D. However, analysis of individual courses in previously depleted patients revealed that serum levels were not restored in three patients (4%) for vitamin A and six patients (66%) for 25-OH-D. A TPN regimen designed to provide the following weekly vitamin quantities: A: 21,000 IU, D: 2100 IU, C: 3500 mg, B12: 126 micrograms, and folate: 7 mg will maintain mean serum vitamin levels for all but 25-OH-D. This regimen has the ability to uniformly restore and maintain vitamins B12, C, and folate in all patients but not in those patients previously deficient in vitamins A and D.

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.

Manipulation of TPN caloric substrate and fatty infiltration of the liver

Hepatic dysfunction frequently develops in severely malnourished patients receiving total parenteral nutrition (TPN) and may limit caloric delivery delaying nutritional repletion. Since hepatic dysfunction may reflect hepatic steatosis due to glucose delivery in excess of oxidative capacity, partial provision of calories as fat may permit increased caloric delivery without hepatic dysfunction. This hypothesis was evaluated using a protein-depleted rat-TPN model. After 4 weeks of protein depletion, rats were nutritionally repleted using one of four isonitrogenous, isovolemic intravenous diets of varying caloric content and/or composition. After 6 days of nutritional repletion massive hepatomegaly and fatty deposition were noted in animals repleted with regimens supplying all nonnitrogenous calories as fat or as carbohydrate (CHO). Hepatic steatosis was avoided when a “balanced” regimen (75% CHO; 25% fat) or a hypocaloric regimen (total calories decreased by 25%) were used, but hypocaloric TPN produced suboptimal nutritional repletion (serum albumin, transferrin, nitrogen balance, weight gain). All intravenous diets were similar to oral rat chow in their ability to restore liver nitrogen and maintain liver protein synthesis. The use of TPN regimens of “balanced” caloric composition similar to that of oral feedings (75% CHO; 25% fat) may provide a clinical alternative to hypocaloric TPN permitting optimal caloric provision and nutritional repletion without hepatic dysfunction.

Protein and Fat Metabolism in Rats during Repletion with Total Parenteral Nutrition (TPN)

We investigated the effect of non-protein calorie source on the repletion by total parenteral nutrition (TPN) of protein-depleted rats. Rats were depleted by feeding them a protein free diet for 4 weeks. Control (non-depleted) and depleted rats were given one of three isocaloric, isonitrogenous TPN regimens for 6 days. They differed in the proportion of non-protein calories given as glucose and fat: diet 1, 100% glucose; diet 2, 75% glucose, 25% fat; and diet 3, 100% fat. The liver, skeletal muscle and whole body protein synthesis and breakdown rates were measured by using [15N]glycine as a tracer. The fatty acid distribution in the liver was measured by gas chromatography-mass spectrometry. Results: (a) Omission of fat leads to a decrease in the fraction of linoleate in the liver. (b) Giving all the non-protein calories as a fat emulsion causes fatty acid accumulation in the liver and a significant increase in the liver protein fractional synthesis rate in the control rats and killed about half the depleted rats. (c) For TPN regimens 1 and 2 both the muscle and whole body synthesis rates were increased during repletion. (d) Of the three TPN regimens, the second one which contained both fat and glucose was superior to the other two.total parenteral nutrition protein synthesis fat

Effect of Carnitine on Liver Fat and Nitrogen Balance in Intravenously Fed Growing Rats

Carnitine is an essential metabolite whose function is to transport activated long-chain fatty acids across the mitochondrial membrane. It is consumed in the diet and is synthesized from lysine and methionine to meet body needs. Hepatic fat deposition has been reported in experimental animals and patients receiving total parenteral nutrition (TPN) fluids devoid of preformed carnitine. In the present experiment, nitrogen balance, hepatic fat deposition and serum and tissue carnitine were determined in rats receiving a hypercaloric TPN regimen containing 0, 10, 50, and 100 mg dl-carnitine per 100 g body weight for 14 days. Rats fed a stock diet served as controls. Increased nitrogen balance was observed in TPN rats receiving the highest dose of carnitine supplementation. Hepatic fat deposition induced by the hypercaloric infusion was ameliorated but not eliminated by infusing carnitine. Serum, liver and skeletal muscle carnitine concentrations were maintained, whereas that of heart decreased in TPN rats without carnitine supplementation. Between 90 and 100% of the administered l-carnitine was excreted. It is suggested that the observed effects of carnitine on nitrogen balance and hepatic fat deposition are due to as yet undefined pharmacological properties. The significant decrease of carnitine in cardiac muscle resulting from TPN in a patient population already stressed and traumatized and the metabolic and physiological effects of this decrease deserve further exploration.total parenteral nutrition carnitine fatty infiltration nitrogen balance

Stability of intravenous fat emulsions.

To the Editor.—Since the reintroduction of fat emulson into the marketplace, surgeons have expressed interest in the compatibility of the product with the dextrose, amino acids, and electrolytes that comprise the balance of total parenteral nutrition regimens. Reports1from Europe have inferred that no overt toxicity is associated with chronic infusion of admixtures containing all these elements; however, these reports lacked a component to characterize the emulsion's ability to withstand the nutrient additives over time. This is a serious consideration since studies2with earlier intravenous (IV) emulsion products found the emulsions to cream and flocculate when admixed with salts of sodium, potassium, and calcium ions. These flocculated products were subsequently found to produce considerable adverse effects (eg, chest pressure, precordial pain, nausea, backache, and dyspnea) on IV infusion. This communication then, is intended to briefly report research undertaken to assess and predict the compatibility of the IV soybean oil

FURTHER STUDIES ON THE GROWTH OF MICRO-ORGANISMS IN TOTAL PARENTERAL NUTRITION SOLUTIONS

Summary The growth of vegetative bacteria in mixtures containing amino acids, dextrose, inorganic salts and vitamins was examined. Escherichia coli and Klebsiella pneumoniae grew rapidly in Aminoplex 14, Vamin-glucose and Aminofusin L600 with 10% w/v dextrose. Growth of E. coli was slower in Synthamin 14 with 10% w/v dextrose. K. pneumoniae was unable to grow in this solution unless vitamins were added. Higher concentrations of dextrose inhibited growth in Synthamin 14, but had little influence on the growth of E. coli or K. pneumoniae in the presence of Vamin-glucose, Aminoplex 14 or Aminofusin L600. Pseudo-monas aeruginosa grew slowly in solutions containing amino acid combinations other than Synthamin 14. Staphylococcus epidermidis was unable to grow in any solutions except those containing Aminofusin L600 where growth was shown to occur only after a long lag phase. Vitamin supplements had little influence on growth rates. No organism was able to grow in any solution stored at 4oC. Results indicate that, to prevent growth of micro-organisms, Total Parenteral Nutrition regimes mixed in 3-1 containers should be stored under refrigeration conditions unless used immediately.

Glucose Tolerance in Very Low Birthweight Infants

Yu, V. Y. H., James, B. E., Hendry, P. G. and MacMahon, R. A. (1979). Aust. Paediatr. J., 15, 147–151 Glucose tolerance in very low birthweight infants. The carbohydrate intake and incidence of hyperglycaemia were reviewed in 40 very low birthweight infants with a birthweight of less than 1200g who were randomly assigned to total parenteral nutrition (TPN) or oral (MILK) feeding regimens during the first two weeks after birth. With increasing glucose tolerance after birth, the carbohydrate intake was increased from a mean intake of 8g/kg.d on Day 1 to 17g/kg.d in the TPN group and 12g/kg.d in the MILK group by the second week; the lower intake in the latter group was due to a restricted intake rather than decreased glucose tolerance. Twenty‐seven per cent of the infants had moderate or severe hyperglycaemia in the first week compared with 13% in the second week, in spite of the higher carbohydrate intake in the latter period. All hyperglycaemic episodes were corrected promptly without obvious serious sequelae by decreasing the rate of carbohydrate intake. The rational approach to carbohydrate administration in the very low birthweight infant includes the calculation of carbohydrate intake in terms of g/kg.d (rather than arbitrary concentrations given at variable rates based on fluid requirement), a constant infusion at a steady rate, and the close monitoring of blood glucose to establish glucose tolerance limits which increase with postnatal age.

Utilization of L-Alanyl-L-Tyrosine by Nephrectomized Rats When Infused as Part of a Total Parenteral Nutrition Regimen

L-Alanyl-L-tyrosine is well utilized as a tyrosine source in parenterally fed rats. Such utilization may depend upon filtration of peptide into the glomerular filtrate, reabsorption into renal epithelial cells, hydrolysis to component amino acids in or at the surface of epithelial cells, and release of component amino acids to the blood. Bilaterially nephrectomized rats were infused with a parenteral solution providing L-alanyl-L-[U-14C]-tyrosine at 0.5 mmoles/kg over a 2 hour period to test this hypothesis. Despite the absence of kidneys, peptide did not accumulate in plasma or tissues. Plasma and liver tyrosine and alanine levels increased significantly over values noted in animals infused without peptide. One-quarter to one-third of the infused radioactivity was released as 14CO2, with the remainder found in the tissues. Between 15 and 51% of radioactivity in individual tissues was free tyrosine, the remainder was incorporated into protein. Isolation of this protein, acid hydrolysis and simultaneous radioactivity-amino acid analysis demonstrated that 94 to 99% of the radioactivity in protein was tyrosine. The data indicate good utilization of alanyl-tyrosine by nephrectomized rats when administered as part of a total parenteral nutrition regimen.

L-alanyl-L-tyrosine as a tyrosine source during total parenteral nutrition. Infusion at 0.5 and 2 mmoles/kg/day in adult rats.

Tyrosine peptides, such as L-alanyl-L-tyrosine, have excellent solubility and are potential sources of iv tyrosine. Infusion of L-alanyl-L-U-14C-tyrosine as part of a total parenteral nutrition regimen in the rat at a level of 0.5 mmole/kg/day resulted in rapid labeling of tissue tyrosine pools, production of 14CO2, incorporation of 14C-labeled tyrosine into protein, and minimal urinary losses (7.7%). Plasma tyrosine levels, however, remained at fasting. Infusion of L-alanyl-L-tyrosine at 2 mmole/kg/day increased plasma tyrosine above fasting levels and maintained tissue tyrosine at levels seen in orally fed control animals without increasing the percent lost in urine (5.5%). Rapid utilization of L-alanyl-L-tyrosine was noted at both infusion levels with no accumulation of peptide noted in plasma. Plasma and tissue free tyrosine pools were rapidly labeled, as was tissue protein. Radioactivity incorporated in tissue protein was shown to be tyrosine after acid hyrolysis.

Essential Fatty Acid Deficiency in Total Parenteral Nutrition Detection by Changes in Intraocular Pressure

Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency.

D-Methionine Utilization During Parenteral Nutrition in Adult Rats

D-Methionine, present in some parenteral solutions, is poorly utilized by man. To evaluate some of the factors affecting utilization, methionine isomer excretion was measured in rats treated with two different parenteral regimens: total parenteral nutrition and protein sparing therapy. Within each regimen, nutrient solutions differing only in methionine isomer composition were compared. Eight rats on the total parenteral nutrition regimen were infused with a 33% glucose--2.8% amino acid solution at a rate providing 100% of energy requirement. Four rats received the parenteral sulution containing L-methionine, and four the solution containing DL-methionine. Eight additional rats on a protein sparing regimen were infused with an amino acid solution (8.5%) at a rate to provide 25% of energy requirement. Four rats were infused with a solution containing L-methionine, and four with a solution containing DL-methionine. Total methionine content of livers was not affected by differences in methionine isomer. Infusion of the solution containing DL-methionine significantly increased plasma methionine levels during protein sparing therapy, with the increase representing accumulation of the D-isomer. Rats receiving protein sparing therapy had significantly higher liver methionine levels than rats receiving total parenteral nutrition. Although rats infused with the solution containing DL-methionine had elevated plasma methionine levels during protein sparing therapy, urinary methionine losses were small, as were losses of methionine sulfoxide and alpha-keto-gamma-methiolbutyrate. In contrast to humans, adult rats utilized more than 99% of parenterally administered D- or L-methionine.

Factors Influencing Essential Fatty Acid Requirement in Total Parenteral Nutrition (TPN)

Twenty patients, after major injuries or elective abdominal surgery, were studied with respect to essential fatty acids in total serum and lipoprotein fractions. The regimen of total parenteral nutrition was altered in its content of energy, carbohydrates or fat. In all patients the linoleic acid levels decreased and the 20:3/20:4 ratio increased. Serum low density lipoproteins developed remarkable alterations of the biochemical composition and of morphology by electronmicroscopy. The degree of these alterations depended on the kind of illness, the amount of carbohydrates infused, special hormonal situation due to surgery and linoleic acid supply. As a consequence of these results, the supply of a sufficient amount of linoleic acid should be considered in every case of total parenteral nutrition.

A computerized scheme for the preparation of parenteral nutrition regimes.

An operational computerized system to aid clinicians in the design of total parenteral nutrition regimes is reported. Two computer programs are described. The 'Requirements' program uses patient data and the results of blood and fluid excretion analyses to calculate the nutritional requirements for a period of 24 hours. Accepted formulae are used in these calculations. The 'Bottle Selection' program fits an intravenous bottle regime to the patient requirements from a standard set of commercially available intravenous feeding solutions. The system has been well accepted by the clinical staff who are free to accept, modify or reject a regime. Financial savings have been noted by the pharmacy who can plan for a faster turnover of a smaller range of solutions. The programs have been used routinely on a programmable calculator and have been written in CORAL for a Ferranti Argus 700E computer.