Neonatal Parenteral Nutrition Research Articles

Quality control of parenteral nutrition compounding: gravimetric and component verification control

Introduction: parenteral nutrition (PN) compounding is a process with a high probability of errors. Objective: to analyze PN compounding errors detected using a gravimetric control (GC) and a component verification control (CVC). Methods: a prospective analysis was carried out during a three-year period (January 2016 to December 2018). The MedicalOne Parenteral® software program was used to calculate the theoretical weight of each PN based on density and volume. Each elaborated PN was weighed to obtain the real weight. Gravimetric error (%) ((real weight - theoretical weight) x 100 / theoretical weight) was considered correct if within the ± 5 % interval. The CVC consisted of checking that the correct ingredients and volumes were added according to the PN order. Results: during the study period a total number of 28,761 PNs were checked out; 20,612 adult PNs (APN) were weighed and 124 were considered incorrect (0.60 %). Of the 1,203 non-neonatal pediatric PNs (NPPN), 15 (1.25 %) were incorrect, and of the 6,946 neonatal PNs (NPN), 164 (2.96 %) were incorrect. Regarding the CVC, 71 errors were detected in the APN (0.70 %), 6 (1.34 %) in the NPPN, and 5 (0.21 %) in the NPN group. The total number of errors included: adding more volume of one component [38 (46.34 %)], adding a wrong component [27 (32.93 %)], and absent volume of one component [17 (20.73 %)]. Conclusions: the quality control carried out allowed to detect errors during the preparation of PNs and prevented them from reaching the patient. More incorrect NPNs were detected through GC. The main error detected with CVC was adding more volume of a component.

Compatibility of Maximum Inorganic and Organic Calcium and Phosphate Content in Neonatal Parenteral Solutions

The purpose of the study was to determine the maximum safe concentration of calcium and phosphate in neonatal parenteral nutrition (PN) solutions when various combinations of inorganic and organic salts are applied. Twelve PN solutions for neonatal use were aseptically prepared. Increasing concentrations of inorganic and organic calcium and phosphate were added to the standard formulas. Each admixture was separately tested according to the following conditions; after mixing, at 37 °C for 24 hr, and the maximum safe combination of calcium and phosphate were stored at 4 °C for 30 days and followed by 24 hr at 37 °C. Visual inspections and microscopic observation of undiluted PN solutions as well as the membrane filter after filtration of the PN solution, pH evaluation, and absorbance were examined. The safe maximum concentration of organic and inorganic calcium and phosphate were proposed individually for each composition of parenteral nutrition solutions. Surprisingly, organic calcium with organic phosphate showed precipitation but over the therapeutic range. The protective effect of amino acid was observed and higher concentrations of calcium and phosphate were free of precipitation. This work is valuable in daily practice as it allows an increase in the limits of calcium and phosphate in PN solutions for infants.

Quantitative Assessment of Trace‐Element Contamination in Parenteral Nutrition Components

Trace-element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace-element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace-element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace-element prescribing in PN. A total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace-element contamination. Trace-element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace-element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively. Trace-element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.

Nutrición parenteral en neonatología: no es una panacea

Nutrición parenteral en neonatología: no es una panacea

Diseño, implementación y análisis de un sistema de cálculo de fórmulas de nutrición parenteral en neonatos con apoyo del farmacéutico

En este estudio se diseñó una hoja de cálculo para formulación de nutriciones parenterales neonatales, en base a los requerimientos sugeridos por la literatura internacional, y se comparó con los datos obtenidos de la formulación por el método manual y una calculadora online. Vale señalar que ni el método manual ni el de la calculadora online consideraban las características de cada marca comercial de los medicamentos usados en las nutriciones parenterales. Esta hoja de cálculo le permitió al farmacéutico acceder a datos relevantes tanto del paciente como de la formulación, lo que redundó en una correcta validación. Se realizó un estudio retrospectivo de 40 nutriciones parenterales neonatales formuladas en el Hospital Luis Gabriel Dávila entre los meses de enero y noviembre de 2014, incluyéndose únicamente los pacientes que recibieron siete o más días de nutrición parenteral.

Improving extrauterine growth: evaluation of an optimized, standardized neonatal parenteral nutrition protocol.

Poor extrauterine growth in very low birth weight (VLBW) neonates is common and associated with worsened long-term outcomes. We aimed to decrease growth restriction, measured by the change in weight z-score from birth to 36 weeks post menstrual age, from - 1.13 (baseline) to < -1 within 12 months. The Model for Improvement was used in the design and implementation of an optimized, standardized parenteral nutrition protocol. Three Plan-Do-Study-Act cycles were completed and a [Formula: see text] and S control chart was created for the primary outcome. Mean weight z-score change from birth to 36 weeks post menstrual age improved by 23% to - 0.87. Improvements in early weight gain and linear growth were seen as well. Use of the Model for Improvement to implement an optimized, standardized parenteral nutrition protocol can help improve extrauterine growth among VLBW infants.

Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All.

Routine administration of trace elements is recognised as a standard of care in children requiring parenteral nutrition. However, there is a lack of global consensus regarding trace elements provision and dosing in pediatric parenteral nutrition. This review provides an overview of available evidence regarding trace elements supply and posology in parenteral nutrition in neonates and children. Trace elements provision in children should be tailored to the weight and clinical condition of the child with emphasis on those at risk of toxicity or deficiency. Based on current evidence, there is a need to review the formulation of commercial solutions that contain multiple-trace elements and to enable individual trace elements additives to be available for specific indications. Literature supports the removal of chromium provision whereas manganese and molybdenum supplementation are debated. Preterm neonates may have higher parenteral requirements in iodine, selenium and copper than previously recommended. There is growing support for the routine provision of iron in long-term parenteral nutrition. Further studies on trace elements contamination of parenteral nutrition solutions are needed for a range of trace elements.

Hypertriglyceridaemia in extremely preterm infants receiving parenteral lipid emulsions

BackgroundLipid emulsions (LE) are routinely administered as part of parenteral nutrition in neonates. There is a wide variation in clinical practice of plasma triglyceride monitoring during LE therapy. Our aim was to evaluate the incidence of hypertriglyceridaemia (Plasma triglyceride > 2.8 mmol/L) and its association with mortality and major morbidities in extremely preterm infants on parenteral nutrition.MethodsA retrospective review of 195 infants < 29 weeks gestation. Lipid emulsion was commenced at 1 g/kg/day soon after birth and increased by 1 g/kg daily up to 3 g/kg/day and continued until the infant was on at least 120 ml/kg/day of enteral feeds. Plasma triglyceride concentrations were measured at each increment and the lipid emulsion dosage was adjusted to keep plasma triglyceride concentrations ≤2.8 mmol/L.ResultsHypertriglyceridemia was noted in 38 neonates (32.5% in 23–25 weeks and 16.1% in 26–28 weeks). Severe hypertriglyceridemia (> 4.5 mmol/L) was noted in 11 infants (10.0% in 23–25 weeks and 4.5% in 26–28 weeks). Hypertriglyceridemia was associated with an increase in mortality (unadjusted OR 3.5; 95% CI 1.13–10.76; 0.033) and severe retinopathy of prematurity (unadjusted OR 4.06; 95% CI 1.73–9.59; 0.002) on univariate analysis. However, this association became non-significant in multivariate analysis with adjustment for gestation and birthweight.ConclusionsHypertriglyceridemia is common in extremely preterm infants receiving parenteral lipid emulsions. Regular monitoring and prompt adjustment of lipid intake in the presence of hypertriglyceridemia, minimising the length of exposure to hypertriglyceridemia, may mitigate potential consequences.

Neonatal Total Parenteral Nutrition: Initiative and implementation of standardized formulation in Saudi Arabia

The total parental nutrition considered as high alert medications for neonates population and others. Several medications safety institutions and international with national accreditation organization recommended setting prevention measure of medical error events. The new medications safety project initiative was neonates standardized parental nutrition formulation. The formulation contained all requirements of American Parenteral and Enteral Nutrition and European Parental and Enteral Nutrition standard. Also, to the United State Pharmacopeia 797 stranded. The formulation is suitable for neonates with formal renal and hepatic functions with common neonate’s requirements Parenteral Nutrition in Saudi Arabia. The new initiative’s project may implement through explored project management tools with close measurements of performance indicators outcome. The neonate’s standardized formulation of parental nutrition new programs at Ministry of Health hospitals in the Kingdom of Saudi Arabia with Gulf and Middle East counties.

Care of infants with gastroschisis in low-resource settings

There is great global disparity in the outcome of infants born with gastroschisis. Mortality approaches 100% in many low income countries. Barriers to better outcomes include lack of antenatal diagnosis, deficient pre-hospital care, ineffective neonatal resuscitation and venous access, limited intensive care facilities, poor access to the operating theatre and safe neonatal anesthesia, and lack of neonatal parenteral nutrition. However, lessons can be learned from the evolution in management of gastroschisis in high-income countries, generic efforts to improve neonatal survival in low- and middle-income countries as well as specific gastroschisis management initiatives in low-resource settings. Micro and meso-level interventions include educational outreach programs, and pre and in hospital management protocols that focus on resuscitation and include the delay or avoidance of early neonatal anesthesia by using a preformed silo or equivalent. Furthermore, multidisciplinary team training, nurse empowerment, and the intentional involvement of mothers in monitoring and care provision may contribute to improving survival. Macro level interventions include the incorporation of ultrasound into World Health Organisation antenatal care guidelines to improve antenatal detection and the establishment of the infrastructure to enable parenteral nutrition provision for neonates in low- and middle-income countries. On a global level, gastroschisis has been suggested as a bellwether condition for evaluating access to and outcomes of neonatal surgical care provision.

Calcium Chloride and Calcium Gluconate in Neonatal Parenteral Nutrition Solutions with Added Cysteine: Compatibility Studies Using Laser Light Obscuration Methodology.

Parenteral nutrition (PN) solutions containing calcium gluconate (CaGlu) and cysteine have elevated particle counts when analyzed using laser light obscuration (LO) as recommended by the United States Pharmacopeia (USP). There are no compatibility studies for solutions compounded with cysteine and containing calcium chloride (CaCl2 ) using LO. The purpose of this study was to conduct compatibility testing for neonatal PN solutions containing CaCl2 and CaGlu with cysteine. Solutions of amino acids (2.5%), containing either CaCl2 or CaGlu plus potassium phosphate, were compounded with 50 and 100 mg/dL cysteine. Solutions were analyzed for particle counts using LO. Maximum concentrations tested were 20 mmol/L calcium and 15 mmol/L phosphate. Three solutions containing CaCl2 (144 total solutions) and 2 containing CaGlu (96 total solutions) and the same concentration of additives were compounded. If the average particle count of replicates exceeded USP guidelines, the solution was incompatible. All solutions containing CaGlu had particle counts that exceeded USP guidelines for particle counts ≥10 μm (range, 86-580 particles/mL). For CaCl2 , 90 of 144 solutions were compatible (range of particle counts for all solutions, 3-121 particles/mL). Maximum compatible concentrations of CaCl2 and potassium phosphate were 15 mmol/L and 12.5 mmol/L, respectively, for solutions containing both 50 and 100 mg/dL cysteine. This study found that neonatal PN solutions containing CaGlu with added cysteine have significantly higher particle counts, exceeding USP guidelines for compatibility, than those containing CaCl2 .

Neonatal and paediatric parenteral nutrition prescription practices in South Africa

Rationale: To describe the current parenteral nutrition (PN) prescription practices and knowledge of prescribers in South Africa and to establish factors which influence usage and adherence to the available guidelines.

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.

Clinical features and practice patterns of gastroschisis: a retrospective analysis using a Japanese national inpatient database.

The number of infants with gastroschisis is increasing worldwide, but advances in neonatal intensive care and parenteral nutrition have reduced gastroschisis mortality. Recent clinical data on gastroschisis are often from Western nations. This study aimed to examine clinical features and practice patterns of gastroschisis in Japan. We examined treatment options, outcomes, and discharge status among inpatients with simple gastroschisis (SG) and complex gastroschisis (CG), 2010-2016, using a national inpatient database in Japan. The 247 eligible patients (222 with SG) had average birth weight of 2102g and average gestational age of 34 weeks; 30% had other congenital anomalies. Digestive anomalies were most common, followed by circulatory anomalies. In-hospital mortality was 8.1%. The median age at start of full enteral feeding was 30days. The median length of stay was 46days. There were no significant differences in outcomes except for length of stay, starting full enteral feeding and total hospitalization costs between the SG and CG groups. About 80% of patients were discharged to home without home medical care. The readmission rate was 28%. This study's findings on the clinical characteristics and outcomes of gastroschisis are useful for the clinical management of gastroschisis.

A New Model for Non-Lipid Compounded Neonatal Parenteral Nutrition Solution Osmolality.

Osmotic stress is a physical risk factor for adverse events related to peripheral parenteral nutrition (PN) administration, such as infiltration. We sought to improve prediction of compounded PN osmolality utilizing basic nutrient solutions available to North American neonatal intensive care units. This study tested the hypothesis that calculated osmolarity underestimates osmolality in compounded PN. Osmolarity (mOsm/L) was calculated utilizing commercial software. Osmolality (mOsm/kg) was determined by a freezing-point depression micro-osmometer. The relationship between calculated osmolarity and measured osmolality was modeled from linear or polynomial regression analysis using the least squares method. Regression models were based upon calculated osmolarity and included various combinations of PN components. Calculated osmolarity significantly underestimated measured osmolality in all PN samples (n = 363). Based upon the osmolality of PN and the basic nutrient solutions, we determined a polynomial regression that effectively corrects for the osmolal gap (measured osmolality-calculated osmolarity) in the validation set (R2 = 0.99367). The unbiased analysis corrected for the osmolal gap based on individual solute behaviors, as well as the solute-solute interactions in compounded solutions. Calculated osmolarity (mOsm/L) significantly underestimates the osmolality (mOsm/kg) in compounded PN. We developed a new algorithm to more accurately predict PN osmolality based upon calculated osmolarity from commercial software and composition of neonatal basic nutrient solutions used in North America. We propose that use of this PN algorithm will facilitate future studies to determine whether a causal association exists between PN osmolality and adverse events, and to establish safe thresholds for PN concentration in neonates.

Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion.

There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid admixture plus vitamins for a period of four hours, which is the maximum time they could be in an admixture during a continuous infusion.

Creatine supplementation to total parenteral nutrition improves creatine status and supports greater liver and kidney protein synthesis in neonatal piglets.

BackgroundCreatine is not included in commercial pediatric parenteral products; the entire creatine requirement must be met by de novo synthesis from arginine during parenteral nutrition (PN). Poor arginine status is common during PN in neonates, which may compromise creatine accretion. We hypothesized that creatine supplementation will improve creatine status and spare arginine in PN-fed piglets.MethodsPiglets (3-5-day (d) old) were provided PN with or without creatine for 14 d. Tissue concentrations of creatine metabolites and activities of creatine-synthesizing enzymes, as well as tissue protein synthesis rates and liver lipid parameters, were measured.ResultsCreatine provision lowered kidney and pancreas L-arginine:glycine amidinotransferase (AGAT, EC number 2.1.4.1) activities and plasma guanidinoacetic acid (GAA) concentration, suggesting the downregulation of de novo creatine synthesis. Creatine increased plasma creatine concentrations to sow-fed reference levels and increased the creatine concentrations in most tissues, but not in the brain. PN creatine resulted in greater protein synthesis in the liver and the kidney, but not in the pancreas, skeletal muscle, or gut. Creatine supplementation also reduced liver cholesterol concentrations, but not triglyceride or total fat.ConclusionThe addition of creatine to PN may optimize the accretion of creatine and reduce the metabolic burden of creatine synthesis in rapidly growing neonates.

Changes in Neonatal Mineral Administration and Contaminant Exposure due to Sodium Phosphate Shortage.

Background National pharmaceutical shortages continue to affect clinical patient care, including neonatal patients. Early postnatal nutrition influences health and growth of infants; quantitative reports describing specific effects of drug shortages on neonatal care are not common. Methods Parenteral nutrition (PN) orders created during the study period were modified to adjust for sodium phosphate unavailability. Original PN orders were collected retrospectively and compared with the modified orders for daily mineral doses, calcium:phosphorus ratio, and potential aluminum exposure. The corrected phosphorus dose was determined to compensate for algorithm-driven changes in phosphorus administration. Results The PN corrected phosphorus dose decreased from 58.9 ± 19.7 mg/kg/day to 42.7 ± 21.7 mg/kg/day (mean ± standard deviation [SD], n = 226 from 22 patients, range, 0–63.4 mg/kg/day, p &lt; 0.05) below the minimal recommended daily dose. There was a coincident doubling of the calcium:phosphorus ratio to &gt; 2.5:1, which was above the desired ratio of 1.8:1. Using potassium phosphate as the only intravenous phosphate source increased the potential aluminum exposure to 60% (9.6 ± 5.0) above the recommended Food And Drug Administration (FDA) limit. Discussion Neonatal PN phosphate administration decreased during the sodium phosphate shortage, raised calcium:phosphate ratios, and increased the potential aluminum exposure. Drug shortages continue to affect preterm infants. Coordinated efforts of health professionals with administrative resources are needed to provide effective short-term solutions and develop long-term strategies. Clinical Relevance Providing optimal PN to neonates is essential for postnatal health and growth. This report describes the effect of a national drug shortage of injectable sodium phosphate on PN composition and infant mineral administration.

Precipitation of Heparin Products With Calcium Gluconate: The Activity of Inactive Ingredients.

Precipitation of Heparin Products With Calcium Gluconate: The Activity of Inactive Ingredients.

A Clinical Audit of Growth and Clinical Outcome in Very Low Birthweight Babies at the Auckland City Hospital Neonatal Intensive Care Unit Before and After the Introduction of SMOFlipid

Introduction: Intestinal failure associated liver disease in very low birthweight (VLBW; birthweight <1,500 g) babies is associated with lipid emulsion use. Multicomponent lipid emulsions may reduce this risk. The aim of this audit was to determine whether a change from a purely soybean oil-based emulsion (Intralipid) to one containing soy, medium-chain triglycerides, olive oil and fish oil (SMOFlipid) would improve growth and clinical outcomes in VLBW babies born at Auckland City Hospital. Method: Consecutively-born VLBW babies were identified from a prospectively-maintained database. Data were collected from electronic clinical records and are presented as mean (SD). Data were available for 105 babies who received Intralipid and 102 babies who received SMOFlipid. Results: Change in Z-scores for weight, length and head circumference between birth and 28 days or discharge did not differ between cohorts. Significantly fewer babies in the SMOFlipid group developed any retinopathy of prematurity (59% vs. 39%, p=0.005) or intraventricular hemorrhage (15% vs. 27%, p=0.03) prior to discharge. Mean total bilirubin levels were similar between cohorts in weeks 1, 2 and 4 after birth, with a significant difference only observed in week 3 (46 (3–203) vs. 42 (1–158) μmol/L, p=0.04). However, repeated measures analyses indicated that both mean (p=0.01), minimum (p=0.03) and maximum (p=0.04) total bilirubin were significantly lower over the first four weeks of life collectively among babies who received SMOFlipid. Conclusion: These data indicate that SMOFlipid may be a favorable alternative to traditional lipid emulsions in neonatal parenteral nutrition regimens. This evidence will be used to inform the guidelines produced by the New Zealand National Intestinal Failure Service.