Parenteral Nutrition Formulations Research Articles

Drug-nutrient Interactions in Elderly Patients

Physiological changes associated with aging affect the absorption, distribution, metabolism, and excretion of drugs and thus therapeutic outcomes. These changes may be further amplified by interactions with nutrients. The purpose of this review was to summarize drug-nutrient interactions found in elderly patients. Mechanisms of the interactions can be categorized as ex vivo bio-inactivations, interactions in absorption and elimination phases, and physiological interactions. The goal of enteral nutrition (EN) is to maximize the therapeutic response of medication without adversely affecting EN tolerance. Therefore, to ensure safety, consistent monitoring is necessary for enteral feeding of patients receiving medication via an enteral tube. Elderly patients receiving parenteral nutrition (PN) are often treated concomitantly with medication via the parenteral route. The stability and compatibility of PN formulations infused with other additives, including medication, may be influenced. Limitation of the number of prescriptions to essential medications only during the minimum period along with periodic re-evaluations of the treatment are thus necessary to minimize undesirable drug-nutrient interactions in elderly patients.

Standardised neonatal parenteral nutrition formulations – an Australasian group consensus 2012

Standardised parenteral nutrition formulations are routinely used in the neonatal intensive care units in Australia and New Zealand. In 2010, a multidisciplinary group was formed to achieve a consensus on the formulations acceptable to majority of the neonatal intensive care units. Literature review was undertaken for each nutrient and recommendations were developed in a series of meetings held between November 2010 and April 2011. Three standard and 2 optional amino acid/dextrose formulations and one lipid emulsion were agreed by majority participants in the consensus. This has a potential to standardise neonatal parenteral nutrition guidelines, reduce costs and prescription errors.

A.S.P.E.N. Clinical Guidelines

Parenteral nutrition (PN) is a high-alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to guide safe use and optimize clinical outcome, several issues are better addressed through evidence-based policies, procedures, and practices. This document provides evidence-based guidance for clinical practices involving PN prescribing, order review, and preparation. A systematic review of the best available evidence was used by an expert work group to answer a series of questions about PN prescribing, order review, compounding, labeling, and dispensing. Concepts from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) format were applied as appropriate. The specific clinical guideline recommendations were developed using consensus prior to review and approval by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. The following questions were addressed: (1) Does education of prescribers improve PN ordering? (2) What is the maximum safe osmolarity of PN admixtures intended for peripheral vein administration? (3) What are the appropriate calcium intake and calcium-phosphate ratios in PN for optimal neonatal bone mineralization? (4) What are the clinical advantages or disadvantages of commercially available premade ("premixed") multichambered PN formulations compared with traditional/customized PN formulations? (5) What are the clinical (infection, catheter occlusion) advantages or disadvantages of 2-in-1 compared with 3-in-1 PN admixtures? (6) What macronutrient dosing limits are expected to provide for the most stable 3-in-1 admixtures? (7) What are the most appropriate recommendations for optimizing calcium (gluconate) and (Na- or K-) phosphate compatibility in PN admixtures? (8) What micronutrient contamination is present in parenteral stock solutions currently used to compound PN admixtures? (9) Is it safe to use the PN admixture as a vehicle for non-nutrient medication delivery? (10) Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis? (11) What methods of repackaging intravenous fat emulsion (IVFE) into smaller patient-specific volumes are safe? (12) What beyond-use date should be used for (a) IVFE dispensed for separate infusion in the original container and (b) repackaged IVFE?

Analysis of the nutritional parameters and adjustment of the requirements of the initial parenteral nutrition in post surgical critically ill patients

To analyze nutritional parameters in critical post-surgical patients under stressful conditions, their evolution, and to assess the degree of adjustment of initial parenteral nutrition (PN) to the requirements set for in the recently published recommendations. Observational, retrospective study including post-surgical critically ill patients admitted to the post-surgical reanimation unit (RU) in whom PN was prescribed, in 2011. Demographical, anthropometric, diagnosis, nutritional parameters, mortality, total duration of hospitalization and duration of hospitalization at the RU, and complications were gathered. The type of PN prescribed was compared, with individualization of the requirements by Kg of body weight, according to the latest recommendations published on nutrition of critically ill patients (ASPEN, ESPEN, SENPE): 18-30 kcal/kg, 0.8-1.5 g/kg/proteins, 4 mg/kg/min/glucose and 2-3 mg/kg/min/glucose in patients with stress-related hyperglycemia, and 0.5-1 g/kg/day of lipids. The variables analyzed were caloric, protein, and glucose adjustments in the initial PN, recovering of albumin > 3 g/dL at day 10, and likely association with the number of complications, mortality and hospital stay. 60 patients were analyzed. 23.3% (14/60) presented hyponutrition at admission, with significant weight loss before the intervention. Albumin, a negative acute phase reactant, was significantly low at baseline, on average 1.9 g/dL (95%CI 1.83-2.12), which indicates a high level of metabolic stress in post-surgical patients. Prescribed PNs were adjusted to the recommendations for kcal, proteins and lipids in 68.3%, 71.7%, and 80.4%, respectively. 57.1% were adjusted for glucose, although the intake from fluid therapy was not taken into account. In patients with a BMI < 22 kg/m2 (16/60), it was observed that 81.8% of the prescribed PNs had an excess in calories, 60% in proteins, and 43.8% in lipids (p < 0.05). 34% of all patients recovered their albumin levels > 3 g/dL at day 10, and the mortality, the duration of hospitalization at the RU, and the number of complications were significantly lower in these patients than in those not recuperating their albumin levels (p < 0.05). Nutritional support is essential, particularly in those patients with a significant level of hyponutrition before surgical intervention, low weighed patients, or in those submitted to gastrointestinal surgery. In our study, baseline PN prescriptions were adjusted to recent recommendations in more than half of the patients; however, in patients with low weight or low BMI we observed higher caloric-protein excess in the prescribed PN since the intake has not been reduced by individualizing it to the body weight. Standardization of PN formulations is a tool of quality and safety, although in these patients it should be individually assessed. More studies are needed to validate the clinical benefits of individualized nutritional intake in post-surgical critically ill patients.

Standardized versus custom parenteral nutrition: Impact on clinical and cost-related outcomes

Results of a study comparing clinical and cost outcomes with the use of standardized versus custom-prepared parenteral nutrition (PN) in an acute care setting are reported. In a retrospective pre-post analysis, nutritional target attainment, electrolyte abnormalities, and other outcomes were compared in patients 15 years of age or older who received custom PN (n = 49) or a standardized PN product (n = 57) for at least 72 hours at a large medical center over a 13-month period; overall, 45% of the cases were intensive care unit (ICU) admissions. A time-and-motion assessment was conducted to determine PN preparation times. There were no significant between-group differences in the percentage of patients who achieved estimated caloric requirements or in mean ICU or hospital length of stay. However, patients who received standardized PN were significantly less likely than those who received custom PN to achieve the highest protein intake goal (63% versus 92%, p = 0.003) and more likely to develop hyponatremia (37% versus 14%, p = 0.01). Pharmacy preparation times averaged 20 minutes for standardized PN and 80 minutes for custom PN; unit costs were $61.06 and $57.84, respectively. A standardized PN formulation was as effective as custom PN in achieving estimated caloric requirements, but it was relatively less effective in achieving 90% of estimated protein requirements and was associated with a higher frequency of hyponatremia. The standardized PN product may be a cost-effective formulation for institutions preparing an average of five or fewer PN orders per day.

Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition

Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN and to quantify any effect on difference in the cost of therapy. We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were potassium chloride, 10 and 20 mEq; magnesium sulfate, 2 g and 4 g; potassium phosphate, 7.5 and 15 mmol; and sodium phosphate, 7.5 and 15 mmol IVPB. There was no statistical difference in the number of PN formulations administered per day during each period (14.7 ± 3.9 vs 14.0 ± 2.6, individualized vs premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 ± 3.8 vs 13.8 ± 6.8; P < .0001). The additional IVPB electrolyte supplementation required in patients receiving premixed PN was associated with an additional $11,855.74 cost per 30 days of therapy compared with those who received individualized PN. Inpatient use of premixed PN results in a significant increase in IVPB electrolyte supplementation and cost compared with individualized PN use.

Ascorbylperoxide from parenteral nutrition induces an increase of redox potential of glutathione and loss of alveoli in newborn guinea pig lungs

BackgroundBronchopulmonary dysplasia is one of the main complications associated with extreme prematurity. Oxidative stress is suspected to be a trigger event of this lung disease, which is characterized by impaired alveolar development. Peroxides, mainly ascorbylperoxide and H2O2, are known contaminant of parenteral nutrition. We hypothesize that these oxidant molecules induce bronchopulmonary dysplasia development. The aim was to determine if the infusion of ascorbylperoxide, whether in presence or absence of H2O2, is associated with oxidative stress, apoptosis and loss of alveoli in the lungs of newborn guinea pigs. MethodThree-day-old guinea pigs received parenteral solutions containing 0, 20, 60 or 180 µM ascorbylperoxide in the presence or not of 350 µM H2O2 (concentrations similar to those measured in parenteral nutrition). After 4 days, the lungs were collected for determination of glutathione's redox potential, caspase-3 activation (an apoptosis marker), alveolarization index (by histology), activation of Nrf2 and NFκB (biological markers of oxidative stress), and IL-6 and PGJ2 levels (markers of NFκB activation). Groups were compared by ANOVA, p < 0.05. ResultsLoss of alveoli was associated with ascorbylperoxide in a dose-dependent manner, without an influence of H2O2. The dose-dependent activation of caspase-3 by ascorbylperoxide was lower in the presence of H2O2. Ascorbylperoxide induced an increase of redox potential in a dose-dependent manner, which reached a plateau in presence of H2O2. Nrf2 and NFκB were activated by H2O2 but not by ascorbylperoxide. ConclusionResults suggest that ascorbylperoxide, generated in parenteral nutrition, is involved in the development of bronchopulmonary dysplasia, independently of the increase of the redox potential. This study underlines the importance of developing a safer formulation of parenteral nutrition.

Commercially Premixed 3-Chamber Bags for Pediatric Parenteral Nutrition Are Available for Hospitalized Children

Hospitalized children are vulnerable to malnutrition during serious illness or recovery from injury and are at subsequent risk of increased morbidity and growth retardation. In cases in which enteral nutrition is not possible, parenteral nutrition (PN) can be used to ensure that patients at nutritional risk receive appropriate amounts of macro- and micronutrients. Nutritional needs cannot be met by 1 standard PN formulation in pediatric patients (term to 18 y) because of the wide range of needs according to age, weight, degree of maturity, and disease state. Preparation of individualized PN is associated with several limitations, including prescribing errors, stability issues, and risk of infection. These risks may be avoided by the availability of a range of pediatric PN formulations provided as commercial premixed 3-chamber bags (3-CBs). These 3-CBs were developed in conjunction with experienced neonatologists and pediatricians in accordance with international guidelines. A prospective study has previously shown the practical handling and ease of use of 2 formulations of these 3-CBs, 1 designed for term infants and toddlers up to 2 y of age and 1 for children and adolescents aged 2–18 y. The majority of pharmacists and nurses described the 3-CB as easy to use and favored it over individual bottles, bags compounded on the ward, ready-to-use compounded bags, and premixes prepared by the pharmacy and tailored to patient needs. These formulations offer a means of improving the quality of care in hospital pediatric units, particularly in the absence of a nutrition support team.

Hypothyroidism and Iodine Deficiency in an Infant Requiring Total Parenteral Nutrition

While iodine deficiency remains a relatively rare cause of thyroid dysfunction in the United States, little is known about iodine status and deficiency in children requiring parenteral nutrition (PN). This population may be at an elevated risk of thyroid dysregulation and neurodevelopmental sequelae due to low concentrations in typical PN formulations. Furthermore, with the widespread practice of switching from iodine-based antiseptics to chlorhexadine, previous inadvertent sources of iodine are being eliminated as well.

Management of parenteral nutrition in intensive care units in Spain

some relevant aspects related to parenteral nutrition in the Spanish ICUs are still unclear. These aspects include: caloric and protein intake, total volume, glycemic control, the type of lipid emulsion used or the comparison of different formulations. Our objective is to know the clinical practice patterns of artificial nutrition therapeutics, particularly of parenteral nutrition in the Spanish ICUs. twelve representative ICU's participated in a nutrition survey from January to March 2012. The survey was divided in two sections: A) Management of artificial nutritional support in critically ill patients and B) Assessment of a new parenteral nutrition formulation adapted to critically ill patients. The following information was collected: percentage of patients receiving artificial nutrition; availability of enteral formulations; types of lipid emulsions; calories, amino acids and lipids supplied; addition of glutamine, vitamins and trace elements; management of volume and hyperglycemia; and comparative data between patients receiving the new formulation vs. standard formulations: glycemic control, assessment of hepatic function and infectious complications as well as the intake of total calories, proteins, volume and insulin supplied. The average number of hospital beds and ICU beds is 780 and 25 respectively; the average number of patients admitted in the ICU is 950 per year. 49% were medical patients, 31% surgical patients and 20% trauma patients. 59.75% of patients required artificial nutrition (AN), of which, 58.7% required enteral nutrition (EN), 16% total parenteral nutrition (TPN); and 25.3% suplementary parenteral nutrition (SPN). When EN was contraindicated, 83.3% of patients were started on early TPN (24 hours) and if EN was not sufficient, 66.7% were started on SPN within 48 hours. Regarding prescribers usual practice, 50% tried to reduce volume of PN and 100% of them had an insulin infusion protocol. 39% of prescribers recommended high-protein, low-volume and low-glucose TPN; 42% prescribe TPN with SMOF (soybean, MCT, olive and fish oil); and 33% with OOBE (olive oil based emulsion) as lipid emulsion. 92% added glutamine. 60% considered that the new formulation may be indicated for sepsis, trauma, burn patients and MOF (multiple organ failure) and the 30% would use it as a routine therapy at the time of admission. 40% considered that insulin requirements were reduced; 50% claimed better volume management and 60% highlighted the protein/volume ratio. Attending to patient outcome, patients receiving the specific formulation have less affected hepatic function, higher protein intake and lower volume infusion but no significant differences were observed and they required less insulin dosage (p = 0.07). In the twelve ICUs included in the survey, the clinical practice patterns related to parenteral nutrition management are adapted to the guidelines of scientific societies such as the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Parenteral and Enteral Nutrition (SENPE) and the European Society for Clinical Nutrition and Metabolism (ESPEN). The new formulations designed for critically ill patients may be indicated for these conditions.

Vigorous periosteal reaction secondary to copper deficiency in an infant on total parenteral nutrition

Sir, We are using this forum to share our recent experience with a 5-month-old child who had dramatic radiographic findings, in order to alert health care workers, including pediatric radiologists, about the increased likelihood of seeing copper deficiency cases in view of the scarcity of parenteral copper. Depending on the supply available, parenteral copper has been frequently omitted from total parenteral nutrition formulations in the last year or so [1]. A 5-month-old boy was transferred to our hospital for intestinal rehabilitation and evaluation for possible intestinal transplantation. He had been born at a gestational age of 34 weeks secondary to preterm labor. Prenatal US was concerning for polyhydramnios and intestinal obstruction. At birth he was found to have multiple small bowel atresias. After multiple surgeries for resections with reanastomosis, he remained dependent on parenteral nutrition and intolerant of enteral feeds. The child had been hospitalized since birth. The original chest/abdomen radiograph at our hospital showed vigorous periosteal reaction of humeri and femurs (sparing the region of the metaphysis) (Fig. 1) along with periosteal reaction of some ribs and the scapulae. Our original differential diagnoses included diffuse osteomyelitis, hypertrophic pulmonary osteoarthropathy, scurvy, vitamin D deficiency and child abuse. A bone survey then revealed osteoporosis (for example, the zone of provisional calcification of knee secondary centers could be seen better than the bone inside) and multiple metaphyseal abnormalities appearing as spurs (Fig. 2) and similar in some locations to “bucket handle” classic metaphyseal lesions of child abuse (Fig. 3). The pattern was somewhat suggestive of scurvy, a disease rarely seen in current practice. The other diagnoses considered were Menkes syndrome (kinky hair syndrome) and copper deficiency from inadequate intake. Vitamin C levels were normal, eliminating scurvy as a diagnosis. Recognition of the national shortage of intravenous micronutrients and trace elements led to evaluation of intake of copper in this boy with intestinal failure who had been dependent on total parenteral nutrition his entire life. It was discovered that because of the national shortage of parenteral copper, he had not received any copper at the referring hospital. A serum copper level showed a very low level of <10 μg/dL (normal 75–165 μg/dL), a very low ceruloplasmin level <4 mg/dL (normal 18–37 mg/dL), and alkaline phosphatase of 1,324 IU/L (normal 82–383 IU/L). Vitamin D, calcium and phosphorus levels were normal. He was anemic (hemoglobin 8.3 g/dL) on admission with normal white blood cell count. In the absence of any enteral feeds and knowledge of absence of copper in the total parenteral nutrition, the radiologic changes were attributed to acquired copper deficiency. Radiologic findings in this boy are consistent with prior reports of profound infantile copper deficiency [2, 3]. The exuberant extent of the periosteal reaction may well relate to the many weeks of normal in-patient handling of the baby without realizing he was bleeding subperiosteally. Copper deficiency leads to reduction of the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the nervous system [4]. Children with deficient copper A. E. Oestreich (*) Department of Radiology, Cincinnati Children’s Hospital Medical Center Radiology 5031 CCHMC, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA e-mail: alan.oestreich@cchmc.org

Probability‐Based Compatibility Curves for Calcium and Phosphates in Parenteral Nutrition Formulations

The information content of the calcium phosphate compatibility curves for adult parenteral nutrition (PN) solutions may benefit from a more sophisticated statistical treatment. Binary logistic regression analyses were evaluated as part of an alternate method for generating formulation compatibility curves. A commercial PN solution was challenged with a systematic array of calcium and phosphate concentrations. These formulations were then characterized for particulates by visual inspection, light obscuration, and filtration followed by optical microscopy. Logistic regression analyses of the data were compared with traditional treatments for generating compatibility curves. Assay-dependent differences were observed in the compatibility curves and associated probability contours; the microscopic method of precipitate detection generated the most robust results. Calcium and phosphate compatibility data generated from small-volume glass containers reasonably predicted the observed compatibility of clinically relevant flexible containers. The published methods for creating calcium and phosphate compatibility curves via connecting the highest passing or lowest failing calcium concentrations should be augmented or replaced by probability contours of the entire experimental design to determine zones of formulation incompatibilities. We recommend researchers evaluate their data with logistic regression analysis to help build a more comprehensive probabilistic database of compatibility information.

A.S.P.E.N. Clinical Guidelines

Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?

Standardised Parenteral Nutrition

Parenteral nutrition (PN) has become an integral part of clinical management of very low birth weight premature neonates. Traditionally different components of PN are prescribed individually considering requirements of an individual neonate (IPN). More recently, standardised PN formulations (SPN) for preterm neonates have been assessed and may have advantages including better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bag that provides total nutrient admixture for neonates may have additional advantage of decreased risk of contamination and ease of administration.

Risk of Parenteral Nutrition in Neonates—An Overview

Healthcare-associated infections (HAI) in preterm infants are a challenge to the care of these fragile patients. HAI-incidence rates range from 6 to 27 infections per 1000 patient-days. Most nosocomial infections are bloodstream infections and of these, the majority is associated with the use of central venous catheters. Many studies identified parenteral nutrition as an independent risk factor for HAI, catheter-associated bloodstream infection, and clinical sepsis. This fact and various published outbreaks due to contaminated parenteral nutrition preparations highlight the importance of appropriate standards in the preparation and handling of intravenous solutions and parenteral nutrition. Ready-to-use parenteral nutrition formulations may provide additional safety in this context. However, there is concern that such formulations may result in overfeeding and necrotizing enterocolitis. Given the risk for catheter-associated infection, handling with parenteral nutrition should be minimized and the duration shortened. Further research is required about this topic.

A.S.P.E.N. Position Paper

The parenteral multivitamin preparations that are commercially available in the United States (U.S.) meet the requirements for most patients who receive parenteral nutrition (PN). However, a separate parenteral vitamin D preparation (cholecalciferol or ergocalciferol) should be made available for treatment of patients with vitamin D deficiency unresponsive to oral vitamin D supplementation. Carnitine is commercially available and should be routinely added to neonatal PN formulations. Choline should also be routinely added to adult and pediatric PN formulations; however, a commercially available parenteral product needs to be developed. The parenteral multi-trace element (TE) preparations that are commercially available in the U.S. require significant modifications. Single-entity trace element products can be used to meet individual patient needs when the multiple-element products are inappropriate (see Summary/A.S.P.E.N. Recommendations section for details of these proposed modifications).

Resolution of Parenteral Nutrition–associated Jaundice on Changing From a Soybean Oil Emulsion to a Complex Mixed‐Lipid Emulsion

Resolution of parenteral nutrition (PN)-associated jaundice has been reported in children given a reduced dose of intravenous fat using a fish oil-derived lipid emulsion. The aim of the present study was to examine the effect on PN-associated jaundice of changing from a soybean oil-derived lipid to a mixed lipid emulsion derived from soybean, coconut, olive, and fish oils without reducing the total amount of lipid given. Retrospective cohort comparison examining serum bilirubin during 6 months in children with PN-associated jaundice who changed to SMOFlipid (n=8) or remained on Intralipid (n=9). At entry, both groups received most of their energy as PN (SMOFlipid 81.5%, range 65.5-100 vs Intralipid 92.2%, range 60.3-100; P=0.37). After 6 months, both tolerated increased enteral feeding but still received large proportions of their energy as PN (SMOFlipid 68.4%, range 36.6-100 vs Intralipid 50%, range 37.6-76; P=0.15). The median bilirubin at the outset was 143 μmol/L (range 71-275) in the SMOFlipid group and 91 μmol/L (range 78-176) in the Intralipid group. After 6 months, 5 of 8 children in the SMOFlipid and 2 of 9 children in the Intralipid group had total resolution of jaundice. The median bilirubin fell by 99 μmol/L in the SMOFlipid group but increased by 79 μmol/L in the Intralipid group (P=0.02). SMOFlipid may have important protective properties for the liver and may constitute a significant advance in PN formulation. Randomised trials are needed to study the efficacy of SMOFlipid in preventing PN liver disease.

Increasing Early Protein Intake Is Associated With a Reduction in Insulin‐Treated Hyperglycemia in Very Preterm Infants

Impaired early protein intake in very preterm infants contributes to early growth failure and may affect long-term neurocognitive development. The authors have previously shown that a standardized concentrated neonatal parenteral nutrition (scNPN) formulation can improve the efficiency of early protein administration. They recognized that very early protein intake could be improved further by modifying the original scNPN regimen and starting PN within 4 hours. To demonstrate that the new scNPN regimen could improve very early protein intake in infants <29 weeks' gestation without causing clinically important PN intolerance and complications. All eligible infants <29 weeks' gestation, receiving the modified scNPN regimen and born between October 2009 and December 2010, were studied (group scNPN2). These were compared with previously studied infants, <29 weeks' gestation and receiving the original scNPN regimen and born between June 2006 and December 2006 (group scNPN1). Infant details, actual nutrition intake, and metabolic/infection data were recorded. Thirty-eight infants <29 weeks' gestation (group scNPN2) were compared with the 38 infants previously studied (group scNPN1). PN was started earlier in group scNPN2, leading to increased mean (95% confidence interval) total protein intake (first 7 days) of 15.3 (14.5-16.1) g/kg in group scNPN2 vs 11.8 (11.0-12.6) g/kg in group scNPN1. There were no differences in calorie, lipid, and carbohydrate intake. Infants receiving insulin for hyperglycemia fell from 20 (53%) in group scNPN1 to 10 (26%) in group scNPN2. Increasing early protein intake is associated with a reduction in insulin-treated hyperglycemia in infants <29 weeks' gestation.

Intestinal Adaptation Is Stimulated by Partial Enteral Nutrition Supplemented With the Prebiotic Short‐Chain Fructooligosaccharide in a Neonatal Intestinal Failure Piglet Model

Butyrate has been shown to stimulate intestinal adaptation when added to parenteral nutrition (PN) following small bowel resection but is not available in current PN formulations. The authors hypothesized that pre- and probiotic administration may be a clinically feasible method to administer butyrate and stimulate intestinal adaptation. Neonatal piglets (48 hours old, n = 87) underwent placement of a jugular catheter and an 80% jejunoileal resection and were randomized to one of the following treatment groups: control (20% standard enteral nutrition/80% standard PN), control plus prebiotic (10 g/L short-chain fructooligosaccharides [scFOS]), control plus probiotic (1 × 10(9) CFU Lactobacillus rhamnosus GG [LGG]), or control plus synbiotic (scFOS + LGG). Animals received infusions for 24 hours, 3 days, or 7 days, and markers of intestinal adaptation were assessed. Prebiotic treatment increased ileal mucosa weight compared with all other treatments (P = .017) and ileal protein compared with control (P = .049), regardless of day. Ileal villus length increased in the prebiotic and synbiotic group (P = .011), regardless of day, specifically due to an increase in epithelial proliferation (P = .003). In the 7-day prebiotic group, peptide transport was upregulated in the jejunum (P = .026), whereas glutamine transport was increased in both the jejunum and colon (P = .001 and .003, respectively). Prebiotic and/or synbiotic supplementation resulted in enhanced structure and function throughout the residual intestine. Identification of a synergistic prebiotic and probiotic combination may enhance the promising results obtained with prebiotic treatment alone.

Influence of the relative composition of trace elements and vitamins in physicochemical stability of total parenteral nutrition formulations for neonatal use.

ObjectiveThe present study aimed to evaluate the influence of the relative composition of trace elements and vitamins in physicochemical stability of neonatal parenteral nutrition.Material and methodsThree formulations for neonatal administration were selected; the main variable was the presence of trace elements and vitamins. The analyses where carried out immediately after preparation and at 24 h, 48 h, 72 h and 7 days after preparation. Three methods were selected to determine globule size: light obscuration, dynamic light scattering and optical microscopy. Complementary evaluation including visual inspection, determination of pH and osmolarity, peroxide levels and measurements of zeta potential were also performed.ResultsThere was an observable alteration in color and phase separation in the PN stored at 25°C and 40°C. Neither globule size pattern, nor any other physicochemical characteristic evaluated appeared to be considerably altered in any of the analyzed formulations even after 7 days of storage at 5°C. Globule size in all the PN studied was consistent with the established limit, below 500 nm by DLS measurement, and PFAT5 was below 0.05% under all storage temperatures.ConclusionConcomitant presence of trace elements and vitamins in the same neonatal formulation did not alter the evaluated aspects of stability.