Parenteral Amino Acid Solutions Research Articles

All-in-One Pediatric Parenteral Nutrition Admixtures with an Extended Shelf Life—Insight in Correlations between Composition and Physicochemical Parameters

The administration of three-in-one parenteral nutrition (PN) admixtures to pediatric patients requires special consideration, specifically concerning quality and physicochemical stability. The introduction of a new parenteral amino acid solution into the market prompted us to evaluate Aminoplasmal Paed-based PN admixtures’ stability. The study aimed to determine the physicochemical parameters of the chosen variations of PN admixtures and search for a correlation between its composition and those parameters. One hundred and sixty-eight variations of PN admixtures intended for patients weighing from 10 to 25 kg and aged from 1 to 12 years and differing in the quantitative composition of electrolytes were selected for the study. The samples were prepared using each of the four intravenous lipid emulsions dedicated to pediatric patients: Intralipid 20%, Clinoleic 20%, Lipidem 20%, and Smoflipid 20%. The stability of the PN admixtures was assessed by visual inspection and determination of pH, osmolality, zeta potential, and hydrodynamic mean droplet diameter (MDD) immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. Pearson’s correlation was used to quantify the relationships between selected ingredients of the PN admixtures and the physicochemical parameters. The PN admixtures were characterized by pH ranging from 5.91 to 7.04, osmolality ranging from 1238 to 1678 mOsm/kg, and zeta potential ranging from −41.3 to −2.16 mV. The changes in pH and osmolality after seven days of storage did not exceed 0.2 and 4.4%, respectively. The homogeneity of the PN admixtures was confirmed by determining the polydispersity index, which ranged from 0.06 to 0.2. The MDD of the studied formulas ranged from 235 to 395 nm and from 233 to 365 nm immediately upon preparation and after the storage period, respectively. Correlations between selected components of the PN admixtures and some physicochemical parameters were found. All Aminoplasmal Paed 10%-based PN admixtures were characterized by appropriate physicochemical quality to be administered via the central veins, both immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. The applied electrolyte concentrations ranges and types of lipid emulsions in the selected macronutrient quantitative compositions allowed the PN admixtures to remain stable for seven days within the specified limits.

Investigation of tryptophan-related yellowing in parenteral amino acid solution: Development of a stability-indicating method and assessment of degradation products in pharmaceutical formulations

Parenteral amino acid solutions containing tryptophan tend to develop a yellow colouration upon storage. Hence, the aim of the present study was to find out whether tryptophan degradation products are the reason for the yellowing. The degree of discolouration and tryptophan degradation was examined by visual examination and UV/Vis measurements with respect to oxygen presence, pH value, and duration of steam sterilization. LC-UV analyses of autoclaved tryptophan solutions indicated eight degradation products, namely R,R/R,S 2-amino-3-(oxoindolin-3-yl)propanoic acid, R,R/R,S 2-amino-3-hydroxy-2-oxoindolin-3-yl)propanoic acids, cis/trans 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid, N´-formylkynurenine, and kynurenine. The proposed degradation products were confirmed by spiking of synthesized degradation products and LC-UV/MS analyses. The LC-UV analysis method was optimized and validated according to the ICH guideline Q2 (R1). Tryptophan stability in commercially available parenteral amino acid formulations was evaluated over a storing period of 12 months in two common types of primary packaging after autoclave procedure.

Two parenteral amino acid solutions and plasma levels of amino acids in the neonate: A randomized trial.

In neonates on total parenteral nutrition (TPN), amino acids may be a risk factor for developing total parenteral nutrition-associated cholestasis (TPNAC). We aimed, first, to compare methionine, cysteine, and taurine plasma levels between neonates on TPN who were receiving an intravenous amino acid solution based on a breast milk aminogram and those on an intravenous solution of pediatric amino acids based on an umbilical cord aminogram, and second, to determine the frequency of TPNAC. A double-blind randomized controlled trial was conducted. Ninety-four neonates with a birthweight of 1000g or more and a gestational age of 30 wk or older were admitted and enrolled. Blood samples were obtained at 0, 7, and 14 d of TPN, and plasma amino acid concentrations were determined by ultra-high-resolution liquid chromatography. Continuous variables were compared using the Wilcoxon rank-sum test or Student's t test; categorical variables were compared using the Fisher exact test. Thirty-five neonates completed the study (Primene, n = 14; TrophAmine, n = 21). On day 14, methionine plasma concentrations were significantly lower in the Primene group than in the TrophAmine group (27 µmol/L versus 32.9 µmol/L, P = 0.044); the taurine concentration was significantly higher in the same group (72.4 µmol/L versus 45.3 µmol/L, P < 0.0001). There were no differences in TPNAC incidence. Administering an intravenous solution of pediatric amino acids based on the umbilical cord aminogram yielded a higher taurine and lower methionine plasma concentration than did administering a similar solution based on the breast milk aminogram.

Maximization of calcium and phosphate in neonatal total parenteral nutrition.

Appropriate calcium and phosphate supplementation is essential for bone growth in preterm infants. Using Rehabix-K2™ (AY Pharmaceuticals, Tokyo, Japan) and Pleamin-P Injection™ (Fuso Pharmaceutical Industries, Osaka, Japan) as the total parenteral nutrition (TPN) and amino acid solution, respectively, we investigated ways of maximizing calcium and phosphate in the TPN solution. Rehabix-K2, Pleamin-P, calcium gluconate, sodium phosphate, 50% glucose, and water were mixed in varying proportions to create 16 formulations. Precipitation assessment was done three times for each of the 16 formulations, and was based on the Japanese Pharmacopeia. Precipitation was observed 24h after mixing when the calcium and phosphate were 60mEq/L and 30mmol/L or 80mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium and phosphate were 20mEq/L and 10mmol/L, respectively. Precipitation was observed once out of three times, when the calcium and phosphate were 40mEq/L and 20mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13 and 6.26, respectively). No precipitation was observed, however, when the calcium and phosphate were 40mEq/L and 20mmol/L, respectively, and the amino acids were 0% and 1% (mean pH, 5.88 and 6.05, respectively). Not only the concentration of calcium and phosphate, but also the pH of the TPN solution, are crucial factors for precipitation. Based on these results, a well-balanced TPN solution maximizing calcium and phosphate availability will be able to be formulated.

Survey of Nutrition Management Practices in Centers for Pediatric Intestinal Rehabilitation.

Nutrition management of pediatric intestinal failure (IF) requires interdisciplinary coordination of parenteral nutrition (PN) and enteral nutrition (EN) support. Nutrition strategies used by specialists in pediatric intestinal rehabilitation to promote gut adaptation and manage complications have not been previously summarized. A practice survey was distributed to members of the dietitian subgroup of the American Society for Parenteral and Enteral Nutrition Pediatric Intestinal Failure Section. The survey included 24 open-ended questions related to PN and enteral feeding strategies, nutrition management of PN-associated liver disease, and laboratory monitoring. Dietitians from 14 centers completed the survey. Management components for patients at risk for cholestasis were consistent and included fat minimization, trace element modification, avoiding PN overfeeding, and providing EN. Parenteral amino acid solutions designed for infants/young children are used in patients <1 or 2 years of age. Trace minerals are dosed individually in 10 of 14 centers. Eleven centers prescribe a continuous infusion of breast milk or elemental formula 1-2 weeks after resection while 3 centers determine the formula type by the extent of resection. Most (86%) centers do not have a protocol for initiating oral/motor therapy. Laboratory panel composition varied widely by center. The selection and frequency of use depended on clinical variables, including cholestatic status, exclusive vs partial PN dependence, postrepletion verification vs routine monitoring, intestinal anatomy, and acuity of care. EN and PN management strategies are relatively consistent among U.S. centers. Collaborative initiatives are necessary to define better practices and establish laboratory monitoring guidelines.

Calorie and Protein Content of Parenteral Amino Acid Solutions.

Nutrition in Clinical PracticeVolume 32, Issue 2 p. 288-288 Letter to the Editor Calorie and Protein Content of Parenteral Amino Acid Solutions L. John Hoffer MD, PhD, L. John Hoffer MD, PhDSearch for more papers by this author L. John Hoffer MD, PhD, L. John Hoffer MD, PhDSearch for more papers by this author First published: 31 March 2017 https://doi.org/10.1177/0884533617692752Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume32, Issue2Tube Feeding ChallengesApril 2017Pages 288-288 RelatedInformation

Parenteral Nutrition: Amino Acids.

There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness.

The effect of two different parenteral nutrition regimens on parenteral nutrition-associated cholestasis

Exposure to parenteral nutrition (PN) is one major factor in the development of cholestasis. The aim of this retrospective study was to compare the effect of these two different PN regimens on PN-associated cholestasis (PNAC). The files of the patients who have received different PN regimens for >14 d in 2005 and 2009 were retrospectively reviewed. 133 patients have received PN more than 14 d. 22 (16.5%) patients had PNAC. 90 neonates were in Group low-dose parenteral (LDpn) and 43 neonates in Group high-dose parenteral. Mean gestational age and birth weight were statistically significantly lower in LDpn Group (p = 0.016, p = 0.434). Cholestasis rate was significantly higher in high dose group. (p = 0.023). Although several risk factors for PNAC are unavoidable, research is still needed to define the optimal parenteral amino acid solution for neonatal patients. Individualized PN may be more affective in allowing growth and minimizing side effects.

Efficacy and safety of a parenteral amino acid solution containing alanyl-glutamine versus standard solution in infants: A first-in-man randomized double-blind trial

Efforts are directed at reaching the optimal composition of pediatric amino acids (AA) infusions. The goal was to demonstrate the safety and efficacy of a newly developed parenteral AA solution containing alanyl-glutamine (GLN-AA) compared to Standard-AA. This is a randomized (2:1), double-blind, multicentre clinical pilot trial. Infants after surgical interventions were allocated to receive GLN-AA or Standard-AA over a minimum of 5 days to maximum of 10 days. AA profiles in blood samples obtained at baseline, day 7, and end of treatment were compared to normal ranges. Data regarding safety, and efficacy were also collected. Infants were comparable for (safety population) gestational age at birth (36 vs 38 weeks), birth weight (2460 vs 2955g), and day of life during start intervention (1 vs 2 days). Plasma AA profiles in infants treated with GLN-AA (n=13) were closer the normal ranges than those in infants treated with Standard-AA (n=6). There were no clinical or statistical differences in adverse events, safety and efficacy parameters between both groups. This first-in-man study shows that GLN-AA is safe in infants after surgical interventions, and is well tolerated. Compared to reference values, GLN-AA better reflects the amino acid requirements of the infant.

Low Iodine Content in the Diets of Hospitalized Preterm Infants

Iodine is critical for normal thyroid hormone synthesis and brain development during infancy, and preterm infants are particularly vulnerable to the effects of both iodine deficiency and excess. Use of iodine-containing skin antiseptics in intensive care nurseries has declined substantially in recent years, but whether the current dietary iodine intake meets the requirement for hospitalized preterm infants is unknown. The aim of the study was to measure the iodine content of enteral and parenteral nutrition products commonly used for hospitalized preterm infants and estimate the daily iodine intake for a hypothetical 1-kg infant. We used mass spectrometry to measure the iodine concentration of seven preterm infant formulas, 10 samples of pooled donor human milk, two human milk fortifiers (HMF) and other enteral supplements, and a parenteral amino acid solution and soy-based lipid emulsion. We calculated the iodine provided by typical diets based on 150 ml/kg · d of formula, donor human milk with or without HMF, and parenteral nutrition. Preterm formula provided 16.4-28.5 μg/d of iodine, whereas unfortified donor human milk provided only 5.0-17.6 μg/d. Adding two servings (six packets) of Similac HMF to human milk increased iodine intake by 11.7 μg/d, whereas adding two servings of Enfamil HMF increased iodine intake by only 0.9 μg/d. The other enteral supplements contained almost no iodine, nor did a parenteral nutrition-based diet. Typical enteral diets for hospitalized preterm infants, particularly those based on donor human milk, provide less than the recommended 30 μg/d of iodine, and parenteral nutrition provides almost no iodine. Additional iodine fortification should be considered.

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.

Comparison of the efficacy of parenteral glutamine and branched-chain amino acid solutions given as extra supplements in parallel to the enteral nutrition in head trauma

Summary Background & aims: We aimed to investigate the effects of parenteral glutamine and parenteral branched-chain amino acid solutions, given as extra supplements to standard enteral nutrition on nutritional parameters like prealbumin, transferrin levels, number of lymphocytes as well as systemic immune response syndrome (SIRS) and sepsis development, mortality and length of stay in ICU in severe head trauma patients.

Neonatal Nutrition and Consequences on Adult Health

After completing this article, readers should be able to: 1. Describe aberrations in adult health that can result from nutrition in the fetal period and in neonatal life. 2. Review the results of studies from human neonates regarding early nutritional interventions designed for “catch-up” growth. 3. Review results from animal studies regarding early nutrition and “programming” for adult metabolic syndrome. 4. Describe some of the potential epigenetic mechanisms that may be responsible for “programming.” 5. Examine methods for preventing growth delays, the consequences of undernutrition, and the metabolic syndrome related to adverse “programming.” One of the traditional goals of neonatal nutrition is to maintain growth within standardized limits. In the preterm infant, growth between the 10th and 90th percentiles of intrauterine rate has been an ideal goal. More recently, maintenance of lean body mass and bone density; prevention of complications such as chronic lung disease, necrotizing enterocolitis, and infection; and optimization of neurodevelopment and adult health through early nutritional programming have become recognized as more meaningful goals than mere somatic growth. To meet these goals, current nutritional practices require thorough scrutiny in terms of quantity and quality (composition) and how they are customized, if not for the individual patient (which would be ideal), at least for subgroups such as those who are small or appropriate for gestational age, sick or healthy, preterm or term, or male or female. Fetal nutrition and development frequently are used as a template for the low-birthweight infant. A large body of literature on the consequences of fetal undernutrition shows that infants born small for gestational age (SGA) not only have short-term morbidity, but long-term morbidity manifested in what has been termed the “metabolic syndrome.” This syndrome includes abdominal obesity, arterial hypertension, and insulin resistance. Other clinical manifestations can be observed, including thyroid dysfunction, hirsutism, ovarian hyperandrogenism and infertility, dyslipidemia (increased …

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.

Amino Acid Needs for Early Growth and Development

Few data exist on amino acid needs in infants and children, mainly because until recently, amino acid requirements were determined using nitrogen balance. The advent of the indicator amino acid oxidation (IAAO) method permits studies to be conducted with minimal adaptation to the test amino acid. In light of the very limited data available for human infants, toddlers, and children, it was proposed that a factorial approach should be used to estimate their essential amino acid requirements. Using amino acid oxidation techniques, dietary essential amino acid requirements in adults have been nearly completed. Data on changes in total body potassium are now available for infants and children. From these data it is possible to calculate protein deposition during growth, and hence, it is now possible to estimate the amino acid requirements in children using a factorial model. However, there has been no independent verification of the model. Recently we determined total branched chain-amino acid requirements for young adults and children, and we can provide data to support the validity of the factorial model. IAAO has been used on children with liver disease as young as 3 y. The minimally invasive IAAO model opens the door for determination of dietary essential amino acid requirements in infants and children during health and disease. For study of preterm neonates, we used a piglet model to show that the amino acid needs for parenteral feeding are markedly reduced for several essential amino acids; this suggests that current commercial total parenteral nutrition amino acid solutions are less than ideal.

HPLC-based method using sample pre-column clean-up for the determination of methanethiol and ethanethiol in parenteral amino acid solutions.

A method has been developed for the chromatographic determination of methanethiol (MT) and ethanethiol (ET) as contaminants in amino acid parenteral nutrition (PN) solutions. The clean-up of the samples before chromatographic analysis was investigated by solid-phase extraction (SPE) on pre-columns filled with polyethylene powder (PE), aluminium oxide (AlOx), silica (SiOx), or polyurethane foam (PUF) as adsorbents. The thiols were more efficiently separated from the matrices by SPE on PUF pre-columns. Simultaneous derivatization and elution with DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) enabled further discrimination between MT and ET by reversed-phase HPLC with spectrophotometric detection. The retention times for the derivatized MT and ET species were 12.5 and 23.0 min, respectively. Recoveries from spiked PN samples were calculated to be approximately 90%, and the MT and ET content of commercial PN solutions was determined using the methodology described. Detection limits of 15 and 10 microg L(-1) were calculated for MT and ET, respectively.

Voltammetric determination of volatile free sulfide and alkylthiols as contaminants in parenteral amino acid solutions

A method for the simultaneous voltammetric determination of free sulfide and volatile alkythiols (methanethiol/ethanethiol) existing as contaminant in parenteral nutrition (PN) solutions was developed. The volatile sulfides (dihydrogensulfide and alkylthiols) formed in the formulations were distilled over 45 min at 47°C in a purpose-made Conway cell. The analytes were quantified by differential pulse cathodic stripping voltametry (DPCSV) at the hanging mercury-drop electrode and determined, simultaneously as dihydrogensulfide and alkylthiols using a 60 s preconcentration time at −300 mV (versus Ag/AgCl, Cl − 3.0 mol l −1). The voltammetric signals were directly linear proportional to the sulfides concentrations in the PN solutions in the range 3–20 μmol l −1 and detection limits of about 2 μmol l −1 were calculated. Recoveries of sulfides from PN solutions in the range 90–110% were calculated using the method and nine commercial PN formulations were analyzed. Methanethiol and ethanethiol were quantified from their composite signals, and the mutual influence of the analytes on the DPCSV measurements is discussed.

Automated polarographic determination of sulfide as contaminant in parenteral amino acid solutions.

A method for the automated polarographic determination of sulfide in a gas-diffusion flow system was developed. The volatile sulfide, existing as a contaminant in parenteral amino acid solutions, was measured after gas diffusion using 0.1 mol l-1 NaOH solution as acceptor. The linear range of calibration, for measurements at a dropping-mercury electrode (DME), was from 5 to 100 micrograms of sulfide with r = 0.999 and RSD = 7.5% (n = 5) for 10 micrograms of sulfide. For measurements at the hanging mercury-drop electrode (HMDE), with a preconcentration time of 30 s, the linear range of calibration was from 0.9 to 20 micrograms of sulfide with r = 0.998 and RSD = 5.8% (n = 5) for 2 micrograms of sulfide. Detection limits of 59 and 11 micrograms l-1 at the DME and HMDE, respectively, were calculated and the recoveries of sulfide from spiked samples were 91.5-104.5%. Parameters that affect the sulfide determination using this method, such as the organic content of the matrix, pH, flow rate and sample size, were investigated.

Parenteral Glycyl-L-Tyrosine Maintains Tyrosine Pools and Supports Growth and Nitrogen Balance in Phenylalanine-Deficient Rats

Poor solubility hampers the addition of sufficient amounts of free tyrosine to parenteral amino acid solutions. We investigated the use of a highly soluble synthetic dipeptide, glycyl-L-tyrosine, as a parenteral tyrosine source in 18 male Wistar rats (body weight 180–200 g). The animals were randomized into three equal groups and catheterized to facilitate isoenergetic (1.2 MJ·kg-1·d-1) and isonitrogenous (1.25 g nitrogen·kg-1·d-1) total parenteral nutrition for 7 d. Controls (Group 1) received a complete amino acid solution, Group 2 received the same solution deficient in phenylalanine (nitrogen replaced with glycine), and group 3 received the phenylalanine-deficient solution supplemented with glycyl-L-tyrosine. Between d 4 and 7, weight gain and nitrogen retention were lower in Group 2 than in Group 1 or 3. In plasma and organ samples obtained at the end of the study, amino acids and dipeptides were analyzed by means of reversed phase-HPLC. In Group 2, phenylalanine and tyrosine concentrations were lower than in controls in plasma, muscle and kidney; in liver, only the tyrosine concentration was lower compared with controls. With glycyl-L-tyrosine supplementation, plasma, liver and kidney tyrosine concentrations and the phenylalanine:tyrosine ratio were normal. Intact glycyl-L-tyrosine was not detectable, suggesting a virtually quantitative elimination or utilization of the infused dipeptide. The results indicate that in phenylalanine-deficient rats, parenteral glycyl-L-tyrosine rapidly provides free tyrosine to facilitate normal growth, promote nitrogen metabolism and maintain intra- and extracellular tyrosine pools.

Hydrogen sulfide in parenteral amino-acid solutions

We have previously reported appreciable concentrations of hydrogen sulfide (H 2S) in paediatric amino-acid solutions, apparently formed from cysteine during the production process. Since manufacturers assured us of their aim to reduce the contents of the potentially toxic H 2S in these solutions, we determined whether lower amounts have been achieved 2 years after our first report. Median H 20S content of 13 paediatric amino-acid solutions was 22.8 μg/I (range: not detectable to > 280 μg/l which is comparable to the amounts previously found. Median H2S content of 8 special solutions for renal and hepatic disorders was 15.8 μg/I (range not detectable to > 280 μg/I). We conclude that manufacturers should make further efforts to reduce H2S amounts in parenteral amino-acid solutions.