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Introduction: Introduction: it is common to add rapid-acting insulin to parenteral nutrition (NP) bags for the management of hyperglycemia. However, insulin can be adsorbed in NP bags due to electrostatic interactions. Objective: to determine the influence of the presence of lipids and of insulin concentration in NP bags on the adsorption of insulin in these bags, as well as its stability for 5 days. Method: seven NP bags were prepared with the same volume and with a similar composition except for the presence of lipids and micronutrients, and insulin concentration. Insulin was determined by electrochemiluminescent immunoassay. Samples of 2 mL were taken after preparation and on day 5. Results: on day 1, the mean loss of insulin was 15.26 % (± 7.08) in the bags with lipids and 18.45 % (± 5.67) (p = 0.60) in the bags without lipids. The percentage of insulin lost by day 5 in the PN bags with lipids was 30.13 % (± 4.14), and in the PN bags without lipids it was 44.71 % (± 12.94) (p = 0,052). No correlation was observed between the amount of insulin added to the PN bags and the percentage of insulin lost between day 1 (ρ = -0.407, p = 0.365) or day 5 (ρ = -0.295, p = 0.521). Conclusions: there is an increase in insulin adsorption in NP EVA bags over time. The presence of lipids in the bags decreases adsorption. Further studies are needed to demonstrate the factors associated with insulin adsorption in EVA bags.

Elneopa NF No. 1 and No. 2 infusions are total parenteral nutrition solutions packaged in four-chambered infusion bags. They have been used as home parenteral nutrition, with various drugs injected into the infusion bags, for treating patient symptoms. In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respective concentrations in the upper and lower chambers also remained unchanged. The concentration of furosemide in the upper chamber of the No. 1 infusion bag decreased after 5 days, although no change was observed in the other chambers and the mixed infusions with the four chambers opened. The concentration of bromhexine hydrochloride slightly decreased in the upper chambers (approximately 3%) after the co-infusion but decreased significantly in the other chambers and the mixed infusions with the four chambers opened. The concentration of metoclopramide hydrochloride significantly decreased in the upper chambers after the co-infusion; however, no change in concentration was observed in the other chambers and the mixed infusion with the four chambers opened. The results of this study provide useful information on home-based parenteral nutrition.

Background: For newborn and preterm infants, standardised and individual parenteral nutrition (PN) is used. PN preparation is at risk for contamination and dosing errors. The quality of PN is crucial for infants and has a direct impact on their health status and safety., Purpose: The aim of this study is to evaluate the physicochemical and microbial quality of PN for newborn and preterm infants prepared on a neonatal ward., Methods: Sampling of various individual PN prepared by nurses on a neonatal ward was performed. Formulations included maximal four electrolytes, variable dextrose and amino acid concentrations. Depending on the sample volume, up to three quality analyses were performed: (1) test for bacterial endotoxins by kinetic-chromogenic method, (2) sterility according to the European and US Pharmacopoeia, and (3) quantification of electrolytes by capillary electrophoresis and of dextrose by ultraviolet detection after enzymatic reaction of hexokinase. The concentrations obtained were evaluated based on the US and Swiss Pharmacopoeia specifications for compounded preparations and compared to the widened pharmacy specifications., Results: The composition of 86% of the 110 analysed PN prepared by nurses on the neonatal ward corresponded to their medical prescription. 14% were out of the acceptable widened pharmacy ranges. We found no microbial contamination in the samples. All PN were free from endotoxins., Conclusion: Component concentrations of PN prepared on wards by nurses differed frequently and significantly from their medical prescription, and the deviation can be critical depending on the component and its mode of action. The sample size is too small to evaluate the microbial contamination., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: High concentrations of trace elements (TE), in particular zinc and selenium, along with carnitine, are often added to parenteral admixtures in paediatric patients on long-term Parenteral Nutrition (PN). We aim to evaluate whether lipid droplet diameters of these admixtures maintain the recommended range of 0.4-1.0 μm., Materials and Methods: Stability studies were carried out on six parenteral admixtures with carnitine, trace elements and electrolytes added in different amounts. Each admixture was formulated with five different lipid emulsions with or without fish oil. Analyses were performed at time 0 (t = 0) and 24, 48, 72, 96 (t = 96) hours after compounding. Droplet diameters were determined by Light Scattering-Reverse Fourier Optics Technique. Samples, stored at 4 °C, were triple tested for a total of 450 analyses. Regression analyses were performed using panel-data techniques., Results: During the 4 days, lipid droplet diameters were in the expected range of 0.4-1.0 μm regardless of trace element and carnitine amounts in all admixtures apart from those containing fish-oil based emulsions and calcium concentrations equal to 4.5 mmol/L. In these latter admixtures, 12% of droplet diameters were larger than 1.0 μm and 2% exceeded 5.0 μm immediately after compounding., Conclusion: Carnitine and high concentrations of trace elements do not affect PN admixtures stability and can be safely infused in long-term home-PN paediatric patients and prematures. Only high calcium concentrations in compresence with fish oil based lipid emulsions seem to change PN stability., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The safe administration of parenteral admixtures should be considered under the headings of physical and chemical stability. Vitamins are considered to be most susceptible to chemical degradation., Objectives: To evaluate the protective effect of UV-protected monolayer ethylene vinyl acetate (EVA) bags in comparison with that of EVA bags without UV protection, on the physicochemical characteristics and stability of the light sensitive vitamins in pediatric parenteral admixtures stored under various temperature and light conditions., Methods: Four different parenteral pediatric admixtures (with trace elements and vitamins) in two types of ethylenovinylacetate (EVA) monolayer containers (with - yellow one and without - transparent one UV protection) were assessed. The physicochemical analyses such as visual inspection, pH and potential zeta measurements, lipid globules size distribution and vitamins concentration were performed at 0 h, 24 h, 8 days and 8 days+24 h after the preparation of the TPN admixtures. In order to quantify ascorbic acid, thiamine and pyridoxine levels, HPLC was used., Results: No differences (p < 0.05) in physicochemical stability of TPN admixtures were noted between two types of EVA bags, with the compositions assessed; stored 8 days (4 °C ± 2) without light plus 24 h at room temperature and light exposure. However significant differences were noticed in ascorbic acid, thiamine and pyridoxine content after 8 days+24 h in comparison with t = 0. This was noted for both for UV-protected bags and bags without UV-protection, Nevertheless, amounts were still within the pharmacopeial range., Conclusions: Both EVA bags under test (with and without UV-protection) ensure physicochemical stability up 8 days at 4 °C ± 2 °C without light exposure and then 24 h at room temperature with light exposure for the total pediatric parenteral admixtures, intended for home parenteral nutrition. Graphical abstract Scheme of physicochemical analysis of parenteral admixtures.

Background: 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 (CaCl 2 ) using LO. The purpose of this study was to conduct compatibility testing for neonatal PN solutions containing CaCl 2 and CaGlu with cysteine., Methods: Solutions of amino acids (2.5%), containing either CaCl 2 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 CaCl 2 (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., Results: All solutions containing CaGlu had particle counts that exceeded USP guidelines for particle counts ≥10 μm (range, 86-580 particles/mL). For CaCl 2 , 90 of 144 solutions were compatible (range of particle counts for all solutions, 3-121 particles/mL). Maximum compatible concentrations of CaCl 2 and potassium phosphate were 15 mmol/L and 12.5 mmol/L, respectively, for solutions containing both 50 and 100 mg/dL cysteine., Conclusion: 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 CaCl 2 ., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objectives: Control of electrolyte concentration in mixtures for parenteral nutrition (MPN) for newborns is crucial before the release of the final product. We aimed to assess the validation of the electrolytes assay in MPN., Methods: Electrolytes assay was performed with Ilyte Analyzer ® . Validation of method was realized in accordance with ICH (International Conference on Harmonization) guideline Q2(R1) and the commission report of the French society of pharmaceutical science and technology. Linearity test solutions were prepared in triplicate using five levels of concentrations for sodium and potassium (60-140% of theoretical concentrations). Accuracy of the method was deducted from the same results of linearity. The intermediate precision was ensured by dosing the main electrolyte in six MPN, during three successive days., Results: Linearity was assessed with correlation coefficients greater than 0.996 for both electrolytes. A non-significant result of comparison test of the intercept with zero (Student test) was obtained. A highly significant result of the test of existence of slopes (Fisher test) proved a linear regression for the 2 electrolytes (P<0.1%). Inter-day precision values were 2.68% and 2.65% respectively for sodium and potassium., Conclusion: The validation of sodium and potassium assay method was successfully performed with Ilyte Analyzer ® allowing routine quality control in MPN., (Copyright © 2018 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

The requirement for visual inspection of pharmaceuticals has been a compendial expectation for over a century, with some advancement of visible particle control strategies in recent years. Current philosophies include a 100% inspection and an Acceptance Sampling Plan inspection. The particles found during these inspections are normally categorized simply by particle size (visible vs. subvisible), particle source (intrinsic vs. extrinsic) and particle type (inherent vs. extraneous). We believe that a more risk- and science-based approach is attainable, which is grounded in forensic data, toxicological/medical opinions and prior knowledge. We have provided an outline for how to determine patient safety impact of visible particles found in parenteral products and potential actions that could be taken within the quality system regarding lot disposition. We believe this approach focuses efforts on patient safety risks, enhances the use of prior knowledge and improves consistency in how particle observations are handled., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Individualized parenteral nutrition is the most specialized type of nutritional support in the hospital setting. The composition and prescribing patterns for parenteral nutrition have evolved due to new emerging scientific evidence. In the last few years, there has been a tendency to increase the nitrogen and lipid content and decrease the carbohydrate content. To assess the prescribing pattern in a tertiary referral hospital in Spain, the nutritional composition of individualized parenteral nutrition was evaluated retrospectively from January to December of 2016. A total of 3029 parenteral nutrition units were analysed, corresponding to 257 hospitalized adult patients. Medical specialists in General Surgery and Haematology were the most common petitioners. The three most frequently prescribed parenteral nutrition formulae contained 13.4 (28.8%), 15.7 (19.54%) and 17.9 (17.79%) g of nitrogen. The quantity of carbohydrates and lipids showed a mean non-protein calories-to-nitrogen ratio of approximately 78:1 and a carbohydrate-to-lipid ratio that was near 50:50 in most cases. These results suggest a trend towards the administration of parenteral nutrition with a high content of nitrogen and smaller proportion of the non-protein components.

Background: Biosynthetic human recombinant short-acting insulin is added to parenteral nutrition (PN) admixtures to nourish glucose-intolerant patients. Insulin, however, is electrostatically attracted and inactivated by ethyl-vinyl-acetate (EVA) bags and filling system tubes. Our aim was to verify and quantify the presence of insulin in PN with and without intravenous lipid emulsion (ILE), just after addition (T0) until the infusion's end (T24)., Methods: Four undiluted samples of 12 different PN complete admixtures (6 with ILE and 6 without), each containing 250 g of glucose in a 2000 mL volume, were taken and analyzed at T0 and T24 by an automated electrochemiluminescence immunoassay after the addition of biosynthetic human recombinant short-acting insulin at increasing doses (from 6 to 72 IU/bag) by an automated compounding device. Assay sensitivity was set at 2 μIU/mL. Admixtures with and without ILE were compared in terms of insulin-detected amounts at T0 and T24., Results: Regardless of the amount initially provided, insulin was missing in PN without ILE. In admixtures with ILE, the greater the insulin and ILE doses initially included, the higher the insulin availability at T0 and T24, both in absolute terms and as a percentage of the initial amount (from 3 to 81% at T0 and from 2.5 to 72.5% at T24). ILE may prevent insulin attraction to plastic surfaces., Conclusions: Insulin is recovered in the presence of ILE in PN even though considerable amounts are untraceable. This aspect needs verification. Until then, insulin should safely be injected in a different manner in uncontrolled situations., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Introduction: Newborn infants and small children require large amounts of calcium and phosphate in a low volume of solution which can increase the risk of precipitation of calcium phosphate. Calcium gluconate is the predominant calcium salt form employed in parenteral nutrition (PN) compounding due to its solubility profile with phosphate. Unfortunately, calcium gluconate contains higher levels of aluminum contamination than calcium chloride, resulting in an increased potential for aluminum toxicity in patients receiving traditional PN. The physicochemical stability of 30 total parenteral admixtures containing inorganic calcium salts was evaluated., Methods: Parenteral admixtures were prepared in one-chamber ethylene vinyl acetate bags: amino acids, glucose, electrolytes including only inorganic calcium salt and 20% (w/w) lipid emulsions (SMOFlipid®, Omegaven® or Lipofundin MCT/LCT®) were placed together in a one chamber bag. Admixtures were stored at +4 °C for up to eight days after preparation. Visual observations, globule size distribution (using optical microscopy, laser diffraction and photon correlation spectroscopy methods), pH analysis and zeta potential measurements were performed., Results: The physicochemical stability of 29 of parenteral admixtures in the presence of inorganic calcium salt was confirmed. One admixture was deemed unsuitable for use in clinical practice due to the coalescence of oil droplets., Conclusion: Despite the presence of inorganic calcium salts, pediatric parenteral admixtures were stable up to eight days of storage. Due to presence of multiple components and a high risk of incompatibilities, physicochemical studies should be performed for each admixture before use in clinical practice.

Aluminum is a common contaminant in many components of parenteral nutrition, especially calcium and phosphate additives. Although long-term effects have been described in the literature, short-term effects are not well-known. Currently, the Food and Drug Administration recommends maintaining aluminum at <5 mcg/kg/day. This was a single center, retrospective case-control study of 102 neonatal intensive care unit patients. Patients were included if they had a diagnosis of necrotizing enterocolitis, rickets/osteopenia, or seizures and received at least 14 days of parenteral nutrition. Patients were matched 1:1 with control patients by gestational age and birth weight. Mean total aluminum exposure for the 14 days of parenteral nutrition was calculated using manufacturer label information. Differences in mean aluminum exposure between cases and controls, as well as subgroup analysis in those with renal impairment or cholestasis, was conducted. Aluminum exposure in patients meeting inclusion criteria closely mirrored the aluminum exposure of control patients. The difference in aluminum exposure was not found to be statistically significant, except in patients with cholestasis. Although the study found no difference in aluminum exposure in short-term complications with neonates, long-term complications are well established and may warrant the need to monitor and limit neonatal aluminum exposure., Competing Interests: The authors declare no conflict of interest.

HPLC coupled to UV diode array detection (DAD) is proposed for the determination of polycyclic aromatic hydrocarbons (PAHs) in pharmaceutical products for parenteral administration. Because rubber is a possible source of PAHs for these products, samples stored in containers with rubber parts were selected for the analysis. The basis for method optimization was EPA Method 8310, which determines 16 priority PAHs in ground water and wastewater by HPLC using both UV and fluorescence detection. Using DAD, two channels were selected for detection, with one operating at 254 nm for the detection of nine PAHs and the other at 225 nm for the detection of seven PAHs. This method allowed for the detection of PAHs using external calibration with LODs and LOQs ranging from 0.001 to 0.060 µg/mL and from 0.003 to 0.167 µg/mL, respectively. Within-day precision, expressed as RSD, varied from 1.24 to 7.76% for PAH concentrations from 0.05 to 0.50 µg/mL, and intraday precision varied from 3.10 to 9.40% for the same concentration range. Method accuracy was confirmed by recoveries of 75-120% of the spiked samples. This method was applied for the determination of PAHs in three commercial infusion solutions and in nine different medications stored in syringes prior to administration to patients. Twelve of 16 PAHs were found in these samples. Total PAH concentrations varied from 0.13 to 13.50 µg/mL. Pyrene was the most prevalent contaminant, being present in 11 of 12 samples in concentrations ranging from 0.17 to 4.80 µg/mL. This method presented good sensitivity for the measurement of PAH in the target samples, allowing for the determination of the 16 priority PAHs in one run and in 30 min.

In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOF TM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The report provides a summary of the presentations at the Virus & TSE Safety Forum 2015 organized by the Parenteral Drug Association (PDA) and held in Cascais, Portugal, from 9 to 11 June, 2015. As with previous conferences of this series, the PDA Virus & TSE Safety Forum 2015 provided an excellent forum for the exchange of information and opinions between the industry, research organizations, and regulatory bodies. Regulatory updates on virus and TSE safety aspects illustrating current topics of discussion at regulatory agencies in Europe and the United States were provided; the conference covered emerging viruses and new virus detection systems that may be used for the investigation of human pathogenic viruses as well as the virus safety of cell substrates and of raw material of ovine/caprine or human origin. Progress of development and use of next-generation sequencing methods was shown by several examples. Virus clearance data illustrating the effectiveness of inactivation or removal methods were presented and data provided giving insight into the mechanism of action of these technologies. In the transmissible spongiform encephalopathy (TSE) part of the conference, the epidemiology of variant Creutzfeldt-Jakob disease was reviewed and an overview about diagnostic tests provided; current thinking about the spread and propagation of prions was presented and the inactivation of prions by disinfection (equipment) and in production of bovine-derived reagents (heparin) shown. The current report provides an overview about the outcomes of the 2015 PDA Virus & TSE Safety Forum, a unique event in this field., (© PDA, Inc. 2016.)

In the production of large-volume parenterals in Japan, equipment and devices such as tanks, pipework, and filters used in production processes are exhaustively cleaned and sterilized, and the cleanliness of water for injection, drug materials, packaging materials, and manufacturing areas is well controlled. In this environment, the bioburden is relatively low, and less heat resistant compared with microorganisms frequently used as biological indicators such as Geobacillus stearothermophilus (ATCC 7953) and Bacillus subtilis 5230 (ATCC 35021). Consequently, the majority of large-volume parenteral solutions in Japan are manufactured under low-heat sterilization conditions of F0 <2 min, so that loss of clarity of solutions and formation of degradation products of constituents are minimized. Bacillus oleronius (ATCC 700005) is listed as a biological indicator in "Guidance on the Manufacture of Sterile Pharmaceutical Products Produced by Terminal Sterilization" (guidance in Japan, issued in 2012). In this study, we investigated whether B. oleronius is an appropriate biological indicator of the efficacy of low-heat, moist-heat sterilization of large-volume parenterals. Specifically, we investigated the spore-forming ability of this microorganism in various cultivation media and measured the D-values and z-values as parameters of heat resistance. The D-values and z-values changed depending on the constituents of large-volume parenteral products. Also, the spores from B. oleronius showed a moist-heat resistance that was similar to or greater than many of the spore-forming organisms isolated from Japanese parenteral manufacturing processes. Taken together, these results indicate that B. oleronius is suitable as a biological indicator for sterility assurance of large-volume parenteral solutions subjected to low-heat, moist-heat terminal sterilization., (© PDA, Inc. 2016.)

Background: Previous studies of compatibility of calcium chloride (CaCl2) and phosphates have not included particle counts in the range specified by the United States Pharmacopeia. Micro-flow imaging techniques have been shown to be comparable to light obscuration when determining particle count and size in pharmaceutical solutions., Objective: The purpose of this study was to do compatibility testing for parenteral nutrition (PN) solutions containing CaCl2 using dynamic light scattering and micro-flow imaging techniques., Methods: Solutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl2, and sodium phosphate (NaPhos) were compounded with and without cysteine. All solutions contained standard additives to neonatal PN solutions including dextrose, trace metals, and electrolytes. Control solutions contained no calcium or phosphate. Solutions were analyzed for particle size and particle count. Means of Z-average particle size and particle counts of controls were determined. Study solutions were compared to controls and United States Pharmacopeia (USP) Chapter 788 guidelines. The maximum amount of Phos that was compatible in solutions that contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined. Compatibility of these solutions was verified by performing analyses of 5 repeats of these solutions. Microscopic analyses of the repeats were also performed., Results: Amounts of CaCl2 and NaPhos that were compatible in solutions containing 1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that could be added to TrophAmine solutions of > = 2.5% AA containing at least 10 mmol/L of CaCl2 was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount of NaPhos that could be added to solutions containing 10 mmol/L of CaCl2 to 10 mmol/L., Conclusion: Calcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus.

Introduction: We have previously reported results of precipitation studies for neonatal parenteral nutrition solutions containing calcium chloride and sodium phosphate using visual methods to determine compatibility. The purpose of this study was to do further testing of compatibility for solutions containing calcium chloride using more sensitive methods., Methods: Solutions of Trophamine (Braun Medical Inc, Irvine, CA) and Premasol (Baxter Pharmaceuticals, Deerfield, IL) were compounded with calcium chloride and potassium phosphate. Controls contained no calcium or phosphate. After incubation at 37° for 24 hours solutions without visual precipitation were analyzed to determine mean particle size using dynamic light scattering from a laser light source., Results: Particle sizes were similar for control solutions and those without visual precipitation and a mean particle size <1000 nm. Compatible solutions were defined as those with added calcium and phosphate with no visual evidence of precipitation and mean particle size <1000 nm. In solutions containing 2.5-3% amino acids and 10 mmol/L of calcium chloride the maximum amount of potassium phosphate that was compatible was 7.5 mmol/L., Conclusion: Maximum amounts of phosphate that could be added to parenteral nutrition solutions containing Trophamine and calcium chloride were about 7.5-10 mmol/L less for a given concentration of calcium based upon laser methodology compared to visual techniques to determine compatibility. There were minor differences in compatibility when adding calcium chloride and potassium phosphate to Premasol versus Trophamine.

Introduction: Pediatric parenteral nutrition enables normal growth even of preterm infants. Those children require, however, tailored parenteral nutrition and the creation of such can be challenging due to the risk of instability and shortages., Objective: Prototypical parenteral admixtures were created using different calcium salts (organic and inorganic) and different lipid emulsions and tested for stability. 36 of parenteral admixtures containing two types of calcium salts: chloride or gluconolactobionate and different lipid emulsions (SMOFlipid® or Lipofundin MCT/LCT®) were under investigation., Methods: Preliminary admixtures were prepared in two-chamber bags whereas lipid emulsions were placed separately in the second chamber. Pre-admixtures were stored for up to 21 days at +4ºC. Contents of the two chambers were combined at t = 0 or after 21 days of storage. Physical analysis of completed admixtures (visual inspection, microscopic observation, pH measurement and determination of the size distribution of oily droplets) was carried out after 21 days of the storage. Stability of lipid, commercial emulsions stored in ethylene vinyl acetate (EVA) bags for 42 days was also studied., Results: Irrespectively of the time of storage of preadmixtures and type of calcium salt and different lipid emulsions among 36 total parenteral admixtures only one showed signs of destabilization after preparation and one was unstable when stored for longer than 14 days. All other formulations were qualified to be stable during the study. All investigated commercial lipid emulsions were physically stable in EVA bags even when stored at room temperature., Conclusion: The study proved that it was possible to store pre-admixture in EVA bags for 21 days at 4°C as well as that CAN (critical aggregation number) and CaxP (the products of multiplication of calcium and phosphate ions concentration) should not be used as reliable indicators of admixture physical stability. No influence of the type of calcium salts on stability of admixtures was observed., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background & Aims: Because lipid putatively encourages contaminant growth it has been proposed that infusion of lipid-containing parenteral nutrition (PN) bags should be restricted to 24 h (48 h or longer if lipid free). This study aimed to examine this proposal by identifying factors affecting Candida albicans growth in PN., Methods: C. albicans growth was assessed in quadruplicate in 12 PN infusates, with and without lipid and varying glucose concentrations., Results: The results are presented as mean ± SEM. Baseline log10 colony forming units (cfu)/mL (1.806 ± 0.015) increased substantially by 48 h in the PN infusates (to 3.731 ± 0.059). In PN infusates (pH 6.14 ± 0.01) growth was unaffected by the presence of 5% w/v lipid (0.246 ± 0.156 log10 cfu/mL decrease; P = 0.127), and independently suppressed by increasing glucose concentration (0.438 ± 0.174 log10 cfu/mL decrease per 10% increase in w/v glucose; P = 0.018). In a separate analysis growth was suppressed by increasing energy density (0.520 ± 0.179 log10 cfu/mL decrease per 1000 kcal non-nitrogen energy in 2 L; P = 0.007), without a significant effect of % non-nitrogen energy from lipid (0.056 ± 0.036 log10 cfu/ml increase per 10%; P = 0.082)., Conclusions: Using a framework developed to examine growth of potential contaminants in PN, the inclusion of lipid emulsion in PN produced no specific effect on the growth of C. albicans, other than by increasing energy density. Growth was independently suppressed by increasing either glucose concentration or non-nitrogen energy density., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: Aluminum (Al) is a toxic element which may contaminate pharmaceutical products used as individual components to prepare total parenteral nutrition mixtures (TPN)., Objectives: 1) to determine Al levels in the individual components used to prepare TPN mixtures; 2) to compare detected Al levels with those imposed by international regulations (FDA); 3) to calculate the total amount of Al administered to adult and children receiving those typical TPN mixtures., Methods: Al was determined by Inductively Coupled Plasma- Atomic Emission Spectrometry (ICP-OES) (Perkin Elmer OPTIMA 5100 DV) in 44 individual products, from different labs and lots, belonging to 16 components available in Argentina: dextrose and amino acids for adult formulas and for pediatric formulas: lípids; potassium chloride; sodium chloride, magnesium sulfate; sodium phosphate; calcium gluconate; sodium glycerophosphate, zinc sulfate; multitrace elements; steril water (ampoules and great volume presentations)., Results: Al levels were detected in 43 of the 44 the studied components, except sterile water. The components of large volume presented between 249 y 1,580 μg Al/ L, between 4 and 180 times FDA established levels (25 μg Al/ L). Small volume components presented Al levels between 85 y 4,909 g/ L, not declared in labels., Conclusions: The highest amounts of Al were detected in calcium gluconate, sodium phosphate and multitrace elements. 2) Usually prescribed TPN mixtures would have higher Al levels than those accepted by FDA regulation; 3) The highest aluminum concentration was provided by dextrose, amino acids and lipids in adult TPN mixtures. In neonate TPN mixtures, Al highest amounts were provided by dextrose and calcium gluconate. The calculated concentration of Al in TPN mixtures was higher than those stipulated by international regulation (5 μg Al/kg (body weight)/ d). It would be advisable for manufacturers to declare the content of aluminum in the label, with the aim of avoiding toxicities which would compromise the critical patients' evolution., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Introduction: The aim of the study was to evaluate stability of 48 total parenteral admixtures for pediatric patients who require home parenteral nutrition. Admixtures contain high amounts of electrolytes. In a clinical practice electrolytes-enrichment of the parenteral nutrition admixtures is a usual demand, especially on the neonatal/pediatric wards. The supplementation of parenteral nutrition with high concentration of electrolytes is a living problem due to decreased stability of lipid emulsions in nutrition admixtures caused by bivalent cations., Methods: Preliminary admixtures were prepared in two-chamber ethylene vinyl acetate bags: amino acids, glucose and electrolytes were combined in one chamber and 20% (w/w) lipid emulsions (SMOFlipid®, Intralipid ® or ClinOleic®) were placed separately in the second chamber. Organic salts of calcium and phosphates were used. Pre-admixtures were stored at +4ºC for up to 21 days after preparation. Each composition of admixtures was prepared twice, because contents of the two chambers were combined at t=0 or after 21 days of storage at +4ºC. Visual observations, globule size distribution (using optical microscopy, laser diffraction and photon correlation spectroscopy methods), pH analyses, zeta potential and surface tension were performed after combining all components together with vitamins., Results: Among 48 of investigated admixtures only two were problematic and other may be stored for at least 21 days at 4°C and completed admixtures demonstrated stability for at least 24 h at room temperature., Conclusion: It was possible to obtain stable admixtures despite of the high concentration of electrolytes., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Aim: To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol., Materials & Methods: Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology., Results: An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time., Conclusion: Ferumoxytol can be used for in vivo tracking of stem cells with MRI.

Unlabelled: The major problem of total parenteral treatment consists in the balancing of the source and dose of the nutritional mixture, so as to not deepen malnutrition with a positive impact on the patients' organism. The aim of the study was to evaluate selected factors that induce hepato-biliary complications in patients treated by means of parenteral nutrition at home., Material and Methods: The retrospective study comprised 70 patients with biochemistry performed every three months. Considering statistical analysis patients were allocated to four groups, depending on the period of treatment. Group A analysis results were based on the activity of aminotransferases, group B on the activity of bilirubin. Both groups A and B were additionally divided into group I where we assigned normal values of control lab results, and group II with improper results after treatment., Results: Differences between groups Ia vs IIa were presented on the basis of the daily supply of glucose: mean- 2.52 vs 3.49 g/kg (p=0.000003), glucose/lipids ratio: mean- 3.76 vs 4.90 g/kg (p=0.0001), daily non-protein energy: mean- 16.73 vs 21.06 kcal/kg (p=0.0001). Differences between groups Ib vs IIb were presented on the basis of the daily supply of glucose: mean- 2.76 vs 3.46 g/kg (p=0.0007), glucose/lipids ratio: mean- 3.98 vs 5.13 g/kg (p=0.01), daily non-protein energy: mean-17.96 vs 20.36 kcal/kg (p=0.04). Based on the above-mentioned analysis the main goal in the prevention of hepatic complications should lead to the reduction of the dose of glucose. Increased glucose supply leads to increased number of hepato-biliary complications., Conclusions: Based on obtained results we were able to conclude that in case of liver complications associated with parenteral nutrition, proper management consists in the modification of nutritional mixtures (reduction in the daily glucose supply and change in the proportions of extra-protein energy). Such management has the greatest clinical effect. When determining the composition of the nutritional mixture one should adjust the glucose supply, so as to offset both sources of extra-protein energy.

Aluminium (Al) toxicity problem in parenteral nutrition solutions (PNS) is decades old and is still unresolved. The aim of this review is to gather updated information about this matter, regarding legislation, manifestations, diagnostics and treatment, patient population at risk and the actions to be taken to limit its accumulation. A structured search using MeSH vocabulary and Title/Abstract searches was conducted in PubMed (http://www.pubmed.gov) up to November 2012. Al is ubiquitous, facilitating its potential for exposure. Nevertheless, humans have several mechanisms to prevent significant absorption and to aid its elimination; therefore, the vast majority of the population is not at risk for Al toxicity. However, when protective gastrointestinal mechanisms are bypassed (for example, parenteral fluids), renal function is impaired (for example, adult patients with renal compromise and neonates) or exposure is high (for example, long-term PNS), Al is prone to accumulate in the body, including manifestations such as impaired neurological development, Alzheimer's disease, metabolic bone disease, dyslipemia and even genotoxic activity. A high Al content in PNS is largely the result of three parenteral nutrient additives: calcium gluconate, inorganic phosphates and cysteine hydrochloride. Despite the legislative efforts, some factors make difficult to comply with the rule and, therefore, to limit the Al toxicity. Unfortunately, manufacturers have not universally changed their processes to obtain a lower Al content of parenteral drug products (PDP). In addition, the imprecise information provided by PDP labels and the high lot-to-lot variation make the prediction of Al content rather inaccurate.

Background & Aims: Recommendations limit infusion of parenteral nutrition (PN) from bags with lipid to 24 h (48 h if lipid free) because lipid putatively encourages contaminant growth. This study aimed to examine these recommendations and identify factors affecting Staphylococcus epidermidis growth in PN., Methods: S. epidermidis growth was assessed in quadruplicate in 12 PN regimens, with and without lipid and varying glucose concentrations., Results: Baseline colony forming units (cfu)/mL (32.6) less than doubled at 48 h in all infusates. In PN infusates (pH 6.2 + 0.02 (SEM)) growth was independently increased by the presence of 5% w/v lipid (14.2 cfu/mL; P = 0.028), and glucose concentration (25.6 cfu/mL per 10% increase in w/v glucose; P = 0.003). In a separate analysis growth was stimulated by energy density (27.7 cfu/1000 kcal non-nitrogen energy in 2 L; P = 0.002), without a significant effect of % non-protein energy from lipid (-2.6 cfu/ml per 10%)., Conclusions: Using a framework developed to examine growth of potential contaminants in PN, no evidence was found to support the specific recommendation to restrict the maximum infusion duration of lipid containing PN to a greater extent than lipid free PN. S. epidermidis growth was not only affected by the presence of lipid, but also glucose concentration and energy density., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The aim of this study was to analyse the composition of parenteral nutrition (PN) mixtures used in the ITU., Methods: Restrospective analysis involved 2124 prescriptions for individual PN bags. They were administered over an 18-month period, to 160 ITU patients with the mean APACHE II score of 26 points (range: 5-61), calculated on admission. The mortality rate was 40%. Nutrition programs were prepared individually following the 2009 ESPEN guidelines. The prescription was modified according to the individual patient's clinical condition. One hundred and sixty prescriptions were analysed on the first day of PN (T1), 139 - on the second day (T2) and 1825 on the third and subsequent days (T3)., Results: The mean energy supplies were: 1381 kcal/day (range: 456-2612) on T1, 1467 kcal/day (range: 524-2860) on T2, and 1654 kcal/day (range: 390-2969) on T3. The mean supplies of amino acids, glucose and lipids were as follows: amino acids 68.3 g/day (range:20-120) on T1; 71.6 g/ day (range:27.5-125) on T2; 88.0 g/day (range:11-196) on T3; glucose 210.25 g/day (range: 120- 400) on T1; 218.34 g/day (range: 65-480) on T2; 278.5 g/day (range: 18-520) on T3; lipids 34.9 g/ day (range: 0-100) on T1; 38.7 g/day (range: 0-100) on T2; 52.66 g/day (range: 0-117) on T3. The percentages of non-protein energy from lipids were: 29.25 (0-73) on T1; 31.58 (range: 0-60) on T2; 33.5 (0-60) on T3. The following statistically significant differences were found: T2-T3- (p<0.05)., Conclusions: The compositions of nutrition bags prepared for ITU patients were consistent with the ESPEN guidelines. The composition varied on different days of nutrition. The differences in the supply of nutrition components indirectly confirm the need for individual prescriptions for ITU patients.

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.