Parenteral Nutrition Regimens Research Articles

Effect of liposomal content of lipid emulsions on plasma lipid concentrations in low birth weight infants receiving parenteral nutrition

We studied the effects of phospholipid liposomes present in intravenously administered lipid emulsions on plasma lipid levels in preterm infants given 10% and 20% lipid emulsions. Twenty premature infants (birth weight 1454 +/- 54 gm) on a parenteral nutrition regimen received up to 4 gm triglycerides per kilogram per day in a 20% lipid emulsion for 2 weeks, and then received the 10% emulsion at 2 gm triglycerides per kilogram per day, which delivered the same total phospholipid load but twice the amount of liposomes. Triglyceride, total cholesterol, and phospholipid concentrations increased significantly when the infants were given 2 gm triglycerides per kilogram per day in the 10% emulsion rather than 4 gm/kg per day in the 20% emulsion (44 +/- 4 to 57 +/- 5 mg/dl, 134 +/- 6 to 162 +/- 9 mg/dl, and 204 +/- 8 to 251 +/- 10 mg/dl, respectively). Lipoprotein analysis indicated the presence of lipoprotein X-like particles in the low-density lipoprotein fraction and an increase of the intermediate-density lipoprotein fraction in infants who received the 10% emulsion. The presence of excess phospholipids in the 10% emulsion was associated with greater plasma lipid alterations. Therefore the use of 20% rather than 10% emulsion allows for more efficient triglyceride clearance, even at a higher triglyceride intake. Administration of emulsions that are relatively poor in phospholipid liposomes may allow delivery of > 2 gm triglycerides per kilogram per day to low birth weight infants.

Safety and efficacy of glycerol and amino acids in combination with lipid emulsion for peripheral parenteral nutrition support.

The safety and efficacy of administering lipid emulsion with ProcalAmine, a glycerol-based parenteral nutrition solution, for peripheral nutrition has not been previously studied. Thirty-four patients recovering from major trauma or surgery were studied while receiving a peripheral parenteral nutrition regimen of either ProcalAmine with 10% lipid emulsion (group 1) or ProcalAmine with 20% lipid emulsion (group 2) for up to 5 days postinjury. Daily dose was 45 mL/kg ProcalAmine, providing 1.35 g of amino acids/kg and 1.35 g of glycero/kg, and 500 mL/day lipid emulsion. The mean daily nitrogen balance was -0.3 g/day in group 1 and -4.1 g/day in group 2. There was no progressive accumulation of circulating glycerol, and urinary glycerol excretion was minimal (less than 0.2 g/day), indicating effective utilization of glycerol as an energy substrate. Our finding that nitrogen balance was better with 10% fat emulsion suggests a limitation in fat utilization in this setting. Both regimens were well tolerated; there were no adverse clinical reactions and no occurrences of phlebitis in either group.

Vitamin E measurement in patients receiving intravenous lipid emulsions.

Two methods for the determination of plasma vitamin E--high-pressure liquid chromatography and spectrophotofluorometry--were compared on samples from four groups of pediatric patients: children and infants receiving lipid emulsion as part of their parenteral nutrition regimen, neonates receiving parenteral nutrition who were not receiving lipid emulsion at the time of blood sampling, and short admission surgery control subjects. In control subjects and patients not receiving lipid emulsions, both methods yielded similar results for vitamin E as alpha-tocopherol. In contrast, in patients receiving lipid emulsion, the fluorometric method yielded values ranging from 200% to 300% greater than did high-pressure liquid chromatography. The source of the discrepancy is most probably the presence of naturally occurring non-alpha-tocopherol isomers in the lipid products, which add to the fluorescent measurement but are resolved by high-pressure liquid chromatography. This study confirms clinically that fluorescent measurement of vitamin E is no longer the method of choice for monitoring tocopherol status in intensive care nurseries.

An indirect calorimetry system for ventilator dependent very low birthweight infants.

With neurodevelopmental outcome of very low birthweight (VLBW) infants being adversely affected by inadequate nutrition during the first few weeks of life, there is an urgent need for more specific nutritional data on the sick VLBW ventilator dependent infant. The development of a new mass spectrometry gas analysis indirect calorimetry system which is non-invasive and can operate over several hours or days is described. Technical evaluation of each of the components of the system indicates a total random error of less than 5%. Systematic error was determined using gas infusions which simulated carbon dioxide production and oxygen consumption. The relative error in the measurement of carbon dioxide production was less than or equal to 1.5% (coefficient of variation (CV) 6.0%)) with carbon dioxide infusion rates ranging from 3.86 to 13.98 ml/min. The relative error in oxygen 'consumption' was less than or equal to 4.3% (CV 2.8%) for infusions of oxygen at rates of 7.5 to 14.80 ml/min. With nitrogen infusions simulating oxygen consumptions of 2.0 and 5.5 ml/min the relative error in the calculated nitrogen infusion was 1.5% (CV 4.1%) and 1.4% (CV 5.7%) respectively. Clinical studies on 10 infants demonstrated a mean energy expenditure of 161.7 kJ/kg/day and a respiratory quotient in excess of 1.0. The energy expenditure of ventilated VLBW infants may be less than previously indicated and the energy mix and nitrogen content of parenteral nutrition regimens recommended for these infants may be inappropriate.

Management of nutritional and infectious complications of postoperative chylothorax in children

Postoperative chylothorax may occur following any intrathoracic surgical procedure in children. From January 1979 through February 1987, 18 children aged 1 month to 9 years had chylothorax listed among their discharge diagnoses. Initial therapy for all patients consisted of chest tube placement for pleural space drainage and nutritional support with either enteral formulas enriched with medium-chain triglycerides or total parenteral nutrition. Both total parenteral nutrition and medium-chain triglyceride-enriched enteral regimens provided adequate nutritional support in these children. Five of the 18 experienced lymphopenia secondary to chylous lymphocyte loss. Infections were diagnosed in 5 patients during hospitalization; one was a fatal viral pneumonitis. No correlation between infectious complications and lymphocyte count could be demonstrated.

Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients

The effects of isocaloric carbohydrate-based vs. fat-based total parenteral nutrition (TPN) regimens on cancer cell proliferation and host nutritional status were evaluated in 27 patients with tumours of the gastro intestinal tract consecutively assigned to receive for 14 days: a glucose-based (A) or a lipid-based (B) TPN formula, or an oral diet (C) isocaloric and isonitrogenous to A and B. Cancer cell replication rate was evaluated by thymidine labelling index (LI) on tumour samples before and at the end of each nutritional regimen. The number of replicating cells increased by 32.2% in patients receiving regimen A. LI decreased by 24.3% in patients given regimen B. LI values were slightly increased (+15%) in patients maintained on regimen C. Nutritional status remained within normal limits. None of the LI changes observed between and within the three arms of the trial were found to be statistically significant. Thus we failed to prove that glucose consistently stimulates or lipids inhibit tumour proliferation despite a trend in this sense.

Intravenous fat emulsions in nutritional support

Intravenous fat emulsions are now used routinely in parenteral nutrition regimens. However, intravenous fat emulsions have a number of toxic effects when given in a conventional manner (ie, as a 6- to 8-hour infusion). Among these effects are impairment of neutrophii and reticuloendothelial function

Nutritional Support and Cancer Cachexia: Evolving Concepts of Mechanisms and Adjunctive Therapies

Despite the widespread employment of intravenous feeding in patients with cancer cachexia to improve outcome, conflicting data exist regarding the efficacy of such therapy in addressing metabolic alterations secondary to immobility, malnutrition, and disease-specific processes. Persistence of distinct abnormalities of body and tissue integrity and peripheral tissue plasma inter-organ nitrogen flux imply the need for anabolic agents to enhance the therapeutic effects of parenteral nutrition. This article focuses upon potential anabolic agents such as chronic submaximal exercise, hormonal augmentation, pharmacologic intervention, and variations in substrate composition. Finally, the immunologic, metabolic, and endocrine consequences of bypassing the gastrointestinal tract are considered and related to the limited efficacy of current total parenteral nutrition regimens.

Comparison of glucose vs. Glucose fat solutions in cancer patients: A controlled crossover study

The purpose of this investigation was to evaluate in a randomised crossover study the effects on nutritional status of two isonitrogenous-isocaloric regimens of total parenteral nutrition (TPN) in 12 severely cachectic cancer patients. The regimens consisted of (1) G: 50 kcal of glucose.kg −1.day −1 + 2g amino-acids.kg −1.day −1 (2) GL: 30 kcal glucose and 20 kcal lipids.kg −1 + 2g amino-acids.kg −1.day −1. Regimens G and GL were delivered sequentially for a period of 10 days each. Six patients (Group A) were randomised to receive regimen G first and regimen GL subsequently. In Group B patients the regimens alternated in the opposite way. The following nutritional variables were measured before TPN, after regimen G and after regimen GL: weight, arm circumference, arm muscle circumference, triceps skin fold, serum proteins, serum albumin, cholinesterase, transferrin, pre-albumin, retinol-binding protein, peripheral lymphocytes, cumulative nitrogen balance and mean urinary excretion of creatinine and 3-methylhistidine. The data showed that body weight and retinol-binding protein significantly increased with both G and GL regimens. No difference was found in the remaining variables, not even when comparing regimen G to GL. Increase in retinol-binding protein and in nitrogen balance were significantly better in the first period of treatment than in the second. These results show that the two regimens had a similar impact on the nutritional status of the cachectic cancer patients and choice between a glucose or a glucose-fat TPN should depend mainly on tolerance of the patients, duration and cost of therapy.

Perdialytic parenteral nutrition with lipids and amino acids in malnourished hemodialysis patients

A 3-mo perdialytic parenteral nutrition (PDPN) regimen was tested in 26 malnourished adults receiving hemodialysis (HD). Subjects were randomly assigned to receive PDPN (n = 12) or not to receive it (n = 14). PDPN was intravenously infused three times a week during HD; each infusion was made up of 1.6 g fat/kg body wt, 0.08 g N/kg body wt, essential and nonessential amino acids, and glycyl-tyrosine. PDPN, together with a PDPN-induced increase in spontaneous eating, increased intakes from 30 +/- 8.4 kcal.kg body wt-1.d-1 (mean +/- SD) and 1 +/- 0.27 g protein.kg body wt-1.d-1 to 39 +/- 8.5 kcal.kg body wt-1.d-1 and 1.25 +/- 0.30 g protein.kg body wt-1.d-1. Compared with control subjects, PDPN patients were characterized by increases in body weight (P less than 0.01), arm-muscle circumference (P less than 0.02), serum transthyretin and albumin concentrations (P less than 0.05), interdialytic creatinine appearance (P less than 0.01), skin-test reactivity (P less than 0.02), plasma leucine (P less than 0.05) without modifications of other amino acids, and plasma apolipoprotein A-I (P less than 0.01) without significant changes in apolipoprotein B, cholesterol, triglyceride, and phospholipid concentrations. Thus, PDPN appeared to be effective and safe with respect to plasma lipids.

Cryptosporidiosis and AIDS

Cryptosporidiosis in patients with AIDS presents as a chronic enteritis, with biliary complications in about 10% of sufferers. The disease is persistent and progressively fatal. Due to the widespread prevalence of the parasite in the community and amongst domesticated animals, persons with AIDS are constantly at risk. Treatment is extremely difficult in view of the apparent lack of a specific anticryptosporidial drug. Methods of immunomodulation are worth considering, but the main recourse may have to be a prolonged regimen of rehydration and parenteral nutrition. However, if T helper cell function improves, the disease may go into remission or the parasite could be eliminated. Vaccination of those at risk is not feasible at present.

Effect of different types of total parenteral nutrition on T-lymphocyte subpopulations and NK cells

Long-chain triglycerides (LCTs) contained in total parenteral nutrition (TPN) regimens provide a considerable energy substrate in malnourished patients. Their effect on the immune system is controversial, however. In this randomized, prospective study we investigated the possible differences between the effect of TPN with LCTs or medium-chain triglycerides (MCTs) on T-lymphocyte subpopulations. Our study included 15 normal subjects, 20 patients receiving glucose-based TPN, and 40 patients receiving glucose-fat-based TPN. In the last group 20 patients received TPN that included LCTs and 20 received 50% MCTs and 50% LCTs. T-lymphocyte subpopulations, including total T cells and T-helper, T-suppressor, and NK cells, as well as the ratio of helper to suppressor T cells were determined before and 10 d after initiation of TPN. We found a significant decrease in the ratio of helper to suppressor T cells in the LCT group although no such difference was detected in the MCT-LCT group. No difference whatever was found in total T cells and helper, suppressor, and NK cells.

Clinical effects and adequacy of a new all-in-one dextrose-electrolyte-trace element preparation in patients on prolonged TPN

We have devised a new all-in-one dextrose/electrolyste/trace element mixture (Polyfusor DY) and tested its efficacy in clinical practice. Polyfusor DY was designed to be combined with an amino-acid preparation and to be infused with lipid in a standard total parenteral nutrition (TPN) regimen. This standard regimen was formulated to provide minimum nitrogen, energy, fluid, electrolyte, vitamin and trace element requirements for the stable patient. The adequacy of currently recommended levels of provision of trace elements was tested in patients receiving long periods of intravenous nutrition. Eleven consecutive patients were fed from 13 to 280 days using TPN prescriptions based on this standard regimen. Two patients died but the nutritional state of the remainder improved. Serum concentrations of zinc, copper, chromium and manganese remained largely within or above the reference ranges, however the selenium content of Polyfusor DY (500 nmol/l) was marginally inadequate to maintain normal biochemistry. Pharmacy compounding time for the standard TPN regimen based on Polyfusor DY was 10.6 ± 0.19 min (mean ± SEM) compared with 22.5 ± 0.30 min for non-standard TPN regimens prescribed independently by other clinicians (P < 0.001). A standard TPN regimen based on Polyfusor DY was clinically effective, in particular giving generally adequate trace element provision with a reduction in pharmacy time and costs.

Effects of Parenteral Amino Acid Nutritional Regimens on Oxidative and Conjugative Drug Metabolism

Our goals were to determine the time-course of the increase in oxidative drug metabolism that occurs when parenteral nutrition is changed from dextrose to amino acids (23% branched-chain), whether the composition of the amino acid regimen influences this effect, and whether drug conjugation is similarly altered. We examined in healthy volunteers the effects of changing isocalorically from intravenous dextrose 440 kcal/day to amino acids, on one occasion 23% branched-chain and on another 85%. The change to the 23% regimen produced a significant increase in metabolic clearance of antipyrine, a model for oxidation (mean +/- SE 3.0 +/- 0.3 to 3.7 +/- 0.4 L/h, N = 6, P less than 0.003), but the change to the 85% regimen did not, indicating that the composition of an amino acid infusion can influence its effect on oxidative metabolism. Analysis of the concentration-time curve for antipyrine after simultaneous dosing and start of the 23% regimen suggests that the increase in metabolic capacity occurred within a few hours. Metabolic clearance of acetaminophen, a model for conjugation, was not altered by changing to either amino acid regimen.

Maintenance of Small Bowel Mucosa with Glutamine‐Enriched Parenteral Nutrition

Glutamine is an important fuel utilized by the intestinal mucosa that is not present in standard amino acid nutrition solutions. In order to determine the effects of glutamine on the intestine, glutamine enriched nutrition was administered intravenously to male Wistar rats. A standard amino acid solution was enriched with 1 and 2 g/100 ml of glutamine or glycine and used as part of a parenteral nutrition regime for 7 days. Intestinal samples were taken for measurements of jejunal weight, DNA, protein, mucosal thickness and villus height. Animals receiving 2 g glutamine/100 ml in the nutrition solution had increased intestinal weight, DNA, and villus height when compared to animals receiving 2 g/100 ml of glycine. No increase in the intestinal parameters was noted when 1 g/100 ml of glutamine was used. To investigate the dose-response effects of glutamine, further studies were performed using isonitrogenous and isocaloric solutions containing 0, 2, and 3 g of glutamine/100 ml. Animals receiving glutamine had a significant increase in mucosal weight, DNA, protein and villus height when compared to animals receiving no glutamine in the parenteral solutions. There was a dose-response relationship between the increase in jejunal DNA and the increased intake of glutamine (r = 0.93, p less than 0.01) but no correlation with the nitrogen content of the solutions (r = 0.18, p = 0.8). Total body nitrogen retention was greater in animals receiving 2 g/100 ml of glutamine (166 +/- 12 mg, days 6/7) when compared to those receiving 0 and 3 g of glutamine/100 ml (126 +/- 14 mg and 138 +/- 16 mg, respectively, p less than 0.05). These studies demonstrate that glutamine enriched nutrition protects against atrophy of the intestinal mucosa and when given at 2 g/100 ml improves nitrogen retention during intravenous feeding.

Structural and functional alterations in the gut of parenterally or enterally fed rats

Various regimens of total parenteral nutrition (TPN) and enteral feeding were compared to determine their effects on the structural and functional changes of rat small intestine. Male Wistar rats, allocated randomly into five groups on the basis of delivery route and composition of nutrients, were fed as follows: standard rat chow ad libitum (CE-2 group), low-residue diet (LRD group), LRD supplemented with 1% (w/v) fiber (LRD + fiber group), elemental diet (ED group), and TPN (TPN group). At 2 weeks of feeding, villi in the terminal ileum decreased in height in the following order: CE-2 group > LRD + fiber group > LRD group > ED group > TPN group. Mucosal diamine oxidase activity remained unchanged in the CE-2 group and LRD + fiber group throughout the experimental period. However, mucosal diamine oxidase values were significantly lower in the remaining three groups, similar to the structural changes, and those values in the ED group were significantly decreased at 2, 3, and 4 weeks. There was a positive correlation between plasma diamine oxidase level and mucosal diamine oxidase content, with a coefficient correlation of y = 0.20 x + 0.03, r = 0.55 ( P < 0.01). These results could be interpreted to indicate that addition of dietary fiber to LRD has a favorable effect on the maintenance of intestinal architecture and function during enteral feeding, and plasma diamine oxidase activity can be used as an index of functional and/or structural changes occurring in the small intestine during enteral or parenteral feedings.

Utilization of intravenously administered N-acetyl- l-glutamine in humans

l-glutamine is too unstable for inclusion in solutions for parenteral nutrition, but its acetylated analogue, N-acetyl- l-glutamine is not. The purpose of this three-part study was to investigate the utilization of intravenously (IV) administered acetylglutamine in humans. In study 1, nine healthy postabsorptive subjects were given 9.4 g acetylglutamine IV during four hours. In study 2, five healthy subjects were studied on two occasions following an overnight fast. They were given 9.4 g of acetylglutamine or an equivalent amount of glutamine as part of a total parenteral nutrition (TPN) regimen during 7.2 hours. A control group of five subjects was given the same TPN regimen, but without acetylglutamine or glutamine. The nutrient solution included glucose, amino acids, and a fat emulsion, supplying 9.4 g nitrogen and 6,300 kJ in a total volume of 1.8 L. In study 3, four patients were studied the day after major surgery. They were given the same TPN regimen as in study 2, containing 9.4 g acetylglutamine, during 7.2 hours. Plasma concentrations and urinary excretion of acetylglutamine and glutamine were measured in all three studies, and so were splanchnic and renal exchange of acetylglutamine and glutamine in study 1. In study 1, the plasma concentration of glutamine rose from 594 ± 28 μmol/L to 728 ± 26 μmol/L ( P < .001), whereas plasma levels of acetylglutamine exceeded 1,000 μmol/L in all subjects at the end of infusion. The eight-hour urinary excretion of acetylglutamine and glutamine corresponded to 18% of the infused amount of acetylglutamine. No net exchange of acetylglutamine across the splanchnic tissues could be determined, but the kidneys extracted acetylglutamine (165 ± 54 μmol/min) and there was a glutamine release (90 ± 10 μmol/min). In study 2, glutamine concentration rose from 537 ± 42 μmol/L to 726 ± 51 μmol/L ( P < .001) when acetylglutamine was infused and from 609 ± 25 μmol/L to 809 ± 42 μmol/L ( P < .001) with glutamine administration. No significant increase in glutamine concentration was found in the control study. Urinary excretion of acetylglutamine and glutamine over 24 hours corresponded to 34% of the administered acetylglutamine dose. In study 3, glutamine concentration was 422 ± 33 μmol/L before infusion and 495 ± 46 μmol/L at the end (ns). Acetylglutamine concentration rose from undetectable values to 517 ± 84 μmol/L. Urinary excretion of acetylglutamine and glutamine during 24 hours corresponded to 41% of the infused amount. The present findings demonstrate that acetylglutamine infusion is accompanied by a rise in arterial glutamine levels after deacetylation of acetylglutamine, primarily in the kidneys. However, 20% to 40% of the administered dose is excreted in urine, rendering acetylglutamine a possible but not ideal glutamine precursor for clinical use.

Do Parenteral Nutrition Solutions with High Concentrations of Branched-Chain Amino Acids Offer Significant Benefits to Stressed Patients?

The critically ill, stressed patient has been characterized as having altered cellular metabolism. Altered protein metabolism is manifested as negative nitrogen balance, reduced whole-body protein synthesis, and increased proteolysis. An increased oxidation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine has also been observed. Exogenous administration of BCAA as part of a total parenteral nutrition (TPN) regimen has been proposed to compensate for the altered protein metabolism in the stressed patient by sparing endogenous sources of BCAA, thereby reducing skeletal muscle catabolism and increasing protein synthesis. Numerous clinical studies have been performed investigating this theory. The results are controversial. Differences in study outcomes appear to be related to study design, especially patient selection. Our review of those studies which were randomized, prospective, and controlled indicates that an improvement in nitrogen retention and visceral protein status can be achieved in stress-stratified patients who receive a TPN regimen containing a BCAA-enriched formula. The significance of these outcomes on morbidity, length of hospital stay, and mortality has not been evaluated.

Nutrient interactions with total parenteral nutrition: Effect of histidine and cysteine intake on urinary zinc excretion

Because cysteine and histidine, two amino acids included in total parenteral nutrition regimens, bind zinc and increase its renal ultrafilterability, my objective was to quantify the effects of infusion of amino acids, including cysteine and histidine, on urinary zinc excretion. The effect of the infusion of high amounts of cysteine and no cysteine (100 mg/kg/day vs none) and of high and low amounts of histidine (165 vs. 95 mg/kg/day) on urinary zinc excretion was determined in 14 newborn infants receiving total parenteral nutrition who had similar zinc intakes (approximately 7 mumol/kg/day). After a 72-hour adaptation period, each infant's urine was collected for two 48-hour periods. Urinary zinc excretion during the high-dose histidine and cysteine infusion periods was significantly elevated compared with that during the no-cysteine and low-dose histidine periods. Therefore concurrent intakes of specific amino acids may have to be considered when zinc dosages are calculated.

Non-protein energy source in parenterally fed weanling rats influences growth, body composition, and skeletal muscle protein turnover

Comparison was made between three total parenteral nutrition (TPN) regimens given to young, weanling rats for 5 days. The three isoenergetic and isonitrogenous regimens contained different ratios of glucose to lipid as non-protein energy sources, being composed of 100% glucose; 67% glucose/33% fat; and 50% glucose/50% fat respectively. Amino acid content was identical for each regimen. Body weight gain, carcass water and energy content, and in vitro skeletal muscle protein synthesis and degradation rates, were measured. All rats gained weight, but those receiving TPN with 100% of non-protein energy as glucose gained the most wet (live) and dry weight. Energetic efficiency was also significantly higher in this group. However, carcass analysis showed that much of the weight gain in this group was probably due to fat deposition. Although the two TPN groups receiving fat emulsion in addition to glucose gained less weight and had lower energetic efficiencies, weight gain was achieved with a comparatively smaller increase in fat deposition compared to the glucose-only group. In vitro rates of protein synthesis in skeletal muscle were significantly higher in the group receiving 100% glucose, but protein degradation rates in this group were grossly elevated. Protein synthesis rates in the groups receiving lipid were less, but degradation rates were also lower. The results suggest that optimal net protein balance in skeletal muscle was achieved in the group receiving 67% glucose: 33% lipid as the non-protein energy source.