Parenteral Amino Acid Mixtures Research Articles

Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino‐acid mixture

Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). The mean Leu concentration at presentation was similar in the groups P and E (1196.9 μmol/L and 1212.2 μmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.

How much protein do parenteral amino acid mixtures provide?

It is commonly assumed that the weight of the amino acids in a parenteral amino acid mixture equals the amount of protein they provide. This assumption ignores the fact that the molecular weight of free amino acids is 18 mass units greater than when they are protein bound. The actual amount of protein substrate provided by commonly used free amino acid mixtures was determined by analyzing the amino acid composition of 3 commonly used parenteral amino acid solutions and the proteins that would be formed from them, and comparing the results with similar data from 3 nutritionally important proteins. After correction for hydration status, the ratio of essential amino acid mass to total mass of the amino acid mixtures was similar to albumin, myosin, and actin. However, all of the amino acid mixtures provided 17% less protein and energy than is now widely assumed. Current parenteral nutrition guidelines recommend 0.8-1.5 g mixed amino acids/kg normal weight per day, on the assumption that they are equivalent to formed proteins, but they are not equivalent. Clinicians who aim to provide 0.8-1.5 g protein/kg must administer 1.0-1.8 g mixed amino acids/kg.

Glutamic Acid and Parenteral Amino Acid Mixtures

Glutamic Acid and Parenteral Amino Acid Mixtures Get access Nutrition Reviews, Volume 8, Issue 1, January 1950, Pages 22–24, https://doi.org/10.1111/j.1753-4887.1950.tb02307.x Published: 01 January 1950

Enteral and parenteral nutrition distinctively modulate intestinal permeability and T cell function in vitro

Nutritional support is an established element of therapy for various indications. However, its impact on the mucosal barrier function is not well understood. We investigated the influence of EN and PN on intestinal epithelial cells and peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC), all of which are involved in the mucosal defense against bacterial translocation and systemic inflammation. Integrity of epithelial cells was measured as transepithelial electrical resistance (TER) of confluent Caco-2 monolayers in the presence of 1% EN, PN and a parenteral amino acid mixture (AM). To determine wound healing capacities, an established migration model with IEC-6 cells was used. Furthermore, we investigated apoptosis, cell activation, proliferation and cytokine secretion of Caco-2, HT29 and of stimulated PBMC and LPMC cultured with or without 1 and 5% EN, AM or PN. We demonstrated that EN, AM and PN promoted the integrity of the epithelial monolayer and reconstituted epithelial cell continuity TGF-beta-dependently and -independently. Interestingly, only PN induced apoptosis and decreased the mitochondrial membrane potential. The activation status of PBMC was significantly reduced by EN and AM. Specifically, EN leads to an increased apoptosis rate, inhibited cell cycle progression and increased pro-inflammatory cytokine secretion. Both EN and PN reduced the activation status and the release of pro- and anti-inflammatory cytokines. Our study provides evidence that by promoting wound healing and regulating T cell function, EN, AM, and PN potently interact with the intestinal barrier and immune system, thus justifying its use in diseases accompanied by impaired mucosal barrier function.

Metabolism of Methionine in the Newborn Infant: Response to the Parenteral and Enteral Administration of Nutrients

The rates of transmethylation and transsulfuration of methionine were quantified using [1-(13)C]methionine and [C2H3]methionine tracers in newborn infants born at term gestation and in prematurely born low birth weight infants. Whole body rate of protein breakdown was also measured using [2H5]phenylalanine. The response to enteral formula feeding and parenteral nutrition was examined in full term and prematurely born babies, respectively. The relative rates of appearance of methionine and phenylalanine were comparable to the amino acid composition of mixed body proteins. Rates of transmethylation were high, both in full term infants (fast 32 +/- 14 micromol kg(-1) x h(-1); fed 21.7 +/- 3.2) and in preterm infants (57.2 +/- 14.8). Significant flux through the transsulfuration pathway was evident (full term: fast 6.0 +/- 4.4, fed 4.1 +/- 2.1; preterm: 24.9 +/- 9.9 micromol kg(-1) x h(-1)). Transsulfuration of methionine is evident in the human newborn in the immediate neonatal period, suggesting that cysteine may not be considered a "conditionally" essential amino acid for the neonate. The high rate of transmethylation may reflect the high methylation demand, whereas high rates of transsulfuration in premature babies may be related to high demands for glutathione and to the amounts of methionine in parenteral amino acid mixtures.

High incidence of hypermethioninaemia in a single neonatal intensive care unit detected by a newly introduced neonatal screening programme

From 1 January 2007 an expanded neonatal screening programme was initiated in the Netherlands, including homocystinuria with methionine as the primary marker. During the first 2 months hypermethioninaemia was detected in 14 newborns who, after proper evaluation, were demonstrated not to have classical homocystinuria. Remarkably, all these children were admitted to a single neonatal intensive care unit (Academic Medical Center, Amsterdam (AMC-NICU)). We evaluated the possible causes for this finding. The cohort of newborns with hypermethioninaemia (group 1) was compared with the cohort of newborns with normal screening results admitted to the AMC-NICU in the same time period (group 2). In addition, parenteral nutrition protocols from all NICUs in the Netherlands were compared. Mean birth weight and gestational age were significantly lower in group 1 than in group 2. All patients in group 1 received parenteral feeding (TPN) at the time of screening and received a higher mean amino acid intake per kilogram body weight than patients receiving TPN in group 2. Also, the AMC-NICU uses a different amino acid mixture for TPN than the other Dutch NICUs, containing more than twice the amount of methionine per gram of amino acids compared with other mixtures. The high incidence of hypermethioninaemia in the AMC-NICU is explained by a combination of low birth weight, low gestational age, and high protein intake supplied by a specific parenteral amino acid mixture containing large amounts of methionine. To prevent hypermethioninaemia, the use of high-methionine containing solutions for TPN should be reconsidered.

Glutamine supplementation in the newborn infant

Glutamine is a non-essential amino acid that can be synthesized de novo from glutamate. This synthesis can be increased by intravenous infusion of carbon precursors (alpha-ketoglutarate or amino acids) in adults and in infants. The metabolism of glutamine is highly compartmentalized between the splanchnic tissues and the periphery, so that orally administered glutamine is completely metabolized in the splanchnic compartment. Data from studies in adults and children show that plasma levels of glutamine decline during acute stress and illness. Because of its importance in several physiological functions (the demonstrated benefits of supplemental glutamine in adult burns and trauma patients and the inhibitory effect on proteolysis in the skeletal muscle in vitro), it has been suggested that during 'acute stress' the demands of glutamine outweigh its de novo synthesis, resulting in a fall in plasma glutamine levels. As a consequence, glutamine has been considered a 'conditionally essential' amino acid. Because of its instability in solution, glutamine is not routinely added to the parenteral amino acid mixtures. A number of clinical trials of parenteral and enteral supplementation of glutamine have been performed. The outcome measures examined have varied between acute effects and long-term complex clinical events such as mortality and risk of infections. Although acute studies in LBW babies have shown some beneficial effects such as changes in protein metabolism and activation of immune system, these have not been translated into prolonged advantages such as reduction in mortality or in nosocomial infection. The reasons for these differences are discussed.

Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials

Studies of biochemical homeostasis and/or body growth have been included as outcome variables in most nutrition trials in paediatric patients. Moreover, these outcome variables have provided important insights into the nutrient requirements of infants and children, and continue to do so. Examples of the value of such studies in improving parenteral nutrition, in defining essential fatty acid metabolism and requirements of infants and in defining the protein and energy needs of low-birth-weight infants are discussed. Data from such studies have helped to define the mechanism of metabolic acidosis and hyperammonaemia associated with the use of early crystalline amino acid mixture and, hence, how to prevent these disorders. Such studies have allowed the development of parenteral amino acid mixtures that circumvent grossly abnormal plasma concentrations of most amino acids and appear to be utilized more efficiently. These studies have also helped define micronutrient requirements, including requirements for several such nutrients that had not been previously recognized as essential (e.g. Cr, Se, Mo, alpha-linolenic acid). Studies of body growth have been particularly valuable in defining the nutritional requirements of low-birth-weight infants. Finally, studies of metabolic homeostasis coupled with more sophisticated metabolic studies have provided considerable insight into the metabolism of the essential fatty acids, linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3). Although such studies have not defined the amount of the longer-chain PUFA synthesized from each of these essential fatty acids, i.e. arachidonic acid (20:4n-6) and DHA (22:6n-3), they have shown that the rates of conversion are extremely variable from infant to infant, suggesting a possible explanation of why some studies show developmental advantages from intake of these fatty acids while others do not.

Effect of Two Amino Acid Solutions on Leucine Turnover in Preterm Infants

Objective: To assess the effect of two different parenteral amino acid mixtures, Trophamine^® and Primene^®, on leucine turnover in preterm infants. Method: Leucine kinetics were measured with [5,5,5 D3]leucine tracer in 15 infants receiving Trophamine (group ‘T’) (mean birth weight 1,263 g) and 22 who received Primene (group ‘P’) (mean birth weight 1,336 g) during two study periods, within a few hours after birth but before introduction of parenteral amino acid solution, and again at postnatal day 7. The rate of appearance of leucine was calculated from the enrichment of α-ketoisocaproic acid in plasma. Results: There were no significant differences in leucine turnover within a few hours after birth in the two groups. In the infants who received Primene leucine turnover on day 7 was significantly lower than in those who received Trophamine (269 ± 43 vs. 335 ± 27, p < 0.05). Despite a higher intake of leucine in the Trophamine group (108 ± 10 vs. 77 ± 8 µmol·kg^–1·h^–1), leucine released from proteins at day 7 was higher in this group compared to Primene (227 ± 27 vs. 192 ± 42 µmol·kg^–1·h^–1). Conclusions: Primene administration results in lower leucine released from proteins, an estimate of protein breakdown, than Trophamine in preterm infants. Increases in whole body leucine turnover in response to administration of i.v. amino acids is influenced by the composition of the amino acid mixture. The factors responsible for this difference remain to be elucidated.

Effect of parenteral amino acids on leucine and urea kinetics in preterm infants

OBJECTIVE: To examine the effect of two commonly used parenteral alimentation amino acid mixtures on whole-body leucine and urea kinetics. METHODS: Ten stable preterm infants were studied during the first 4 weeks after birth. Six infants received a mixture containing higher branched-chain amino acids, lower glycine plus added dicarboxylic acids formulation (Trophamine), and four received a standard amino acid mixture (Aminosyn). Whole-body protein turnover was measured with [1- 13C]leucine tracer, and the rate of oxidation of protein was calculated by quantifying the appearance of carbon 13 from leucine in carbon dioxide as well as from rates of urea synthesis estimated by using [ 15N 2]urea tracer. Energy consumption and substrate oxidation were quantified by indirect respiratory calorimetry. Infants were given similar quantities of energy (≈61 kcal/kg per day), glucose (≈10.7 mg/kg per minute) and protein (≈2.1 gm/kg per day). RESULTS: There was no significant difference in the rate of appearance of leucine in the two groups. However, the fraction of leucine oxidized ( p = 0.002) and total rate of oxidation of leucine was higher in the Trophamine group. Thus additional branched-chain amino acids resulted in an increased contribution of C-1 of leucine to expired CO 2. The rate of urea N synthesis was also similar in the two groups (Trophamine: 2.92 ± 0.87 mg N/kg per hour; Aminosyn: 2.70 ± 1.18 mg N/kg per hour). CONCLUSIONS: Although the use of Trophamine normalizes the blood amino acid pattern, it does not appear to improve nitrogen/protein kinetics. Furthermore, the additional branched-chain amino acids are disposed of by increased oxidation. (J P EDIATR 1996;128:130-4)

Modulation of thermogenic response to parenteral amino acid infusion in surgical stress

Thermogenic response to parenteral infusion of amino acid mixtures in rats undergoing surgical stress was investigated with the aid of a small animal indirect calorimeter. Male Wistar rats ( n = 12) were laparotomized and received intestinal abrasion along with construction of a parenteral route. After 48 h, nutrient-induced thermogenesis (NIT) produced by amino acid mixtures was examined and compared with that of control rats ( n = 12) without surgical stress. The NIT values of the leucine-enriched solution were greater than those of the control solution in both rats with and without surgical stress. The NIT generated by the leucine-enriched solution in rats with surgical stress was significantly higher than that in rats without. NIT values for 10 different kinds of single amino acid solutions with identical concentrations was then examined in 60 rats. The NIT values of the leucine and the glycine solutions were relatively higher than those of other solutions. However, when puromycin was injected intraperitoneally into 12 rats just before measurement of the NIT in response to amino acid mixtures, no significant differences were found in NIT values between the mixtures. In summary, surgical stress increased the thermogenic response to the leucine-enriched solution, indicating that utilization of leucine may be augmented under surgical stress. In fact, leucine itself may be a thermogenic amino acid. Inhibition of protein synthesis prevented the increase in thermogenic response induced by the leucine-enriched solution. We conclude that thermogenic responses to parenteral amino acid mixtures may differ depending not only upon the compositions of amino acids but also upon the host conditions.

Amino Acid and Energy Needs of Pediatric Patients Receiving Parenteral Nutrition

The technique of parenteral nutrition has become such an established part of modern pediatric care that it is difficult to imagine how pediatricians, as recently as 25 years ago, managed a large group of very difficult patients; however, despite its obvious nutritional advantages, the technique is not without problems. Many of these can be circumvented or controlled by careful attention to all aspects of the technique. Certainly the incidence of these problems can be maintained at a level sufficiently low that the benefits of the technique far outweigh its risks; however, the technique clearly can be further improved. One requirement for doing so is to recognize that the technique is deceptively simple and that it should not be used indiscriminantly without careful consideration of indications and alternative strategies for nutritional management. Additional research also is required. As discussed earlier, the available parenteral amino acid mixtures and lipid emulsions, although considerably improved over earlier versions, remain far from optimal. Some of the actual and theoretic problems that should be addressed in the near future are discussed in the preceding sections; there also are many others.

Use of a Pediatric Parenteral Amino Acid Mixture in a Population of Extremely Low Birth Weight Neonates: Frequency and Spectrum of Direct Bilirubinemia

This retrospective study demonstrates a low frequency of parenteral nutrition-associated direct bilirubinemia within a population of extremely low birthweight neonates (1000 gm or less) exposed to a pediatric amino acid mixture.

TrophAmine

In Reply.— The purpose of the study reported in the paper1 to which Zlotkin refers was to evaluate the efficacy of a new parenteral amino acid mixture (ie, TrophAmine) with respect to maintaining "normal" plasma amino acid concentrations and promoting nitrogen retention in low birth weight infants. Because the study was not a controlled trial in which this amino acid mixture was compared with another mixture, a concerted effort was made to avoid drawing conclusions or stating claims regarding the efficacy of this amino acid mixture relative to other mixtures.

TrophAmine

To the Editor.— Heird et al1 recently described the use of a new parenteral amino acid mixture for low birth weight infants which included a peptide of tyrosine (N-acetyl-l-tyrosine). They concluded that infants tolerated the new mixture well and stated that it was "more efficacious with respect to nitrogen retention and weight gain than other available mixtures." It is my contention that their results do not substantiate their claims. First, the efficiency of nitrogen retention with TrophAmine (70% retention) is not superior to older amino acid solutions.

The isolated perfused rat liver: Conceptual and practical considerations

The isolated perfused rat liver: Conceptual and practical considerations

Inhibition of bile flow in the isolated perfused rat liver by a synthetic parenteral amino acid mixture: associated net amino acid fluxes.

To identify a role for amino acids in cholestasis associated with total parenteral nutrition, we measured bile formation by the isolated perfused rat liver in the presence and absence of added amino acids. All livers were infused constantly with sodium [14C]taurocholate (0.28 mumoles per min) for 90 min. At 40 min, a primed-constant infusion of a synthetic L-amino acid mixture (121 + 19.3 mumoles of N per min) was administered for an additional 50 min. Mean bile flow rates during the amino acid infusion were reduced from 15.4 microliter per min per 10 gm liver weight to 10.4 microliter per min per 10 gm (p less than 0.005). There was no significant change during saline infusion of control livers, and there was no significant difference in perfusate osmolalities in the two groups. Although biliary recovery of infused taurocholate was slightly lower in the experimental perfusions than in controls (95.3% vs. 101.7%, p less than 0.05), there was no significant reduction in taurocholate excretion rate during the infusion in either group. Bile flow changes were related to ambient concentrations and net fluxes of individual amino acids in the perfusate. Of the 14 infused amino acids, glycine and arginine achieved levels greater than 3 times greater than reported physiological postprandial portal venous concentrations in the rat, and together constituted about 25% of the 90-min perfusate amino acids (8.3 mM). The highest net hepatic uptake was for glycine (125 mumoles per hr per 10 gm), which was almost 50% of its infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acid mixtures as parenteral protein food

Review of the literature since 1945 has confirmed previous studies regarding the safety and utility of appropriate amino acid mixtures as parenteral protein food. The addition of such solutions to the parenteral fluids given for purposes of maintenance assures an almost complete nutritional intake during periods when the patient is unable to take anything by mouth and/or when we wish to keep the gastrointestinal tract completely at rest. Supplementary protein alimentation may also be useful by this method. Use of parenteral amino acid mixtures enables the physician to treat disease without protein starvation. Since protein starvation is known to be detrimental, the boundaries of surgical or medical therapy, previously limited thereby, can now be greatly extended.