Determinación de insulina en bolsas multicapa de nutrición parenteral / Measurement of insulin in multilayer bags for parenteral nutrition

Introducción: es habitual adicionar insulina de acción rápida a las bolsas de nutrición parenteral (NP) para el manejo de la hiperglucemia. Sin embargo, la insulina puede adsorberse en las bolsas de NP debido a interacciones electroestáticas. Objetivo: determinar la estabilidad a 5 días y la influencia de la presencia de lípidos y de la concentración de insulina en las NP sobre la adsorción de insulina en las bolsas de NP. Método: se elaboraron 7 NP con el mismo volumen y con una composición semejante exceptuando la presencia de lípidos, los micronutrientes y la concentración de insulina. Se determinó la insulina mediante un inmunoensayo inmunométrico de electroquimioluminiscencia (ECLIA). Se tomaron muestras de 2 mL tras su preparación y en el día 5. Resultados: en el día 1, la pérdida media de insulina fue del 15,26 % (± 7,08) en las bolsas con lípidos y del 18,45 % (± 5,67) (p = 0,60) en las bolsas sin lípidos. El porcentaje de insulina perdido el día 5 en las NP con lípidos fue del 30,13 % (± 4,14) y en las NP sin lípidos del 44,71 % (± 12,94) (p = 0,052). No se observó correlación entre la cantidad de insulina adicionada a las bolsas de NP y el porcentaje perdido de insulina entre el día 1 (ρ = -0,407, p = 0,365), ni el día 5 (ρ = -0,295, p = 0,521). Conclusiones: hay un aumento de la adsorción de insulina en las bolsas de NP de etilenvinilacetato (EVA) con el paso del tiempo. La presencia de lípidos en las bolsas disminuye la adsorción. Son necesarios más estudios para demostrar cuáles son los factores asociados a la adsorción de insulina en las bolsas de EVA. (AU)

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. (AU)

[Stability of Six Drugs in Total Parenteral Nutrition Solution].

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.

[Measurement of insulin in multilayer bags for parenteral nutrition]. / Determinación de insulina en bolsas multicapa de nutrición parenteral.

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.

INTRODUCCIÓN: Introducción: es habitual adicionar insulina de acción rápida a las bolsas de nutrición parenteral (NP) para el manejo de la hiperglucemia. Sin embargo, la insulina puede adsorberse en las bolsas de NP debido a interacciones electroestáticas. Objetivo: determinar la estabilidad a 5 días y la influencia de la presencia de lípidos y de la concentración de insulina en las NP sobre la adsorción de insulina en las bolsas de NP. Método: se elaboraron 7 NP con el mismo volumen y con una composición semejante exceptuando la presencia de lípidos, los micronutrientes y la concentración de insulina. Se determinó la insulina mediante un inmunoensayo inmunométrico de electroquimioluminiscencia (ECLIA). Se tomaron muestras de 2 mL tras su preparación y en el día 5. Resultados: en el día 1, la pérdida media de insulina fue del 15,26 % (± 7,08) en las bolsas con lípidos y del 18,45 % (± 5,67) (p = 0,60) en las bolsas sin lípidos. El porcentaje de insulina perdido el día 5 en las NP con lípidos fue del 30,13 % (± 4,14) y en las NP sin lípidos del 44,71 % (± 12,94) (p = 0,052). No se observó correlación entre la cantidad de insulina adicionada a las bolsas de NP y el porcentaje perdido de insulina entre el día 1 (ρ = -0,407, p = 0,365), ni el día 5 (ρ = -0,295, p = 0,521). Conclusiones: hay un aumento de la adsorción de insulina en las bolsas de NP de etilenvinilacetato (EVA) con el paso del tiempo. La presencia de lípidos en las bolsas disminuye la adsorción. Son necesarios más estudios para demostrar cuáles son los factores asociados a la adsorción de insulina en las bolsas de EVA.

Quality and safety of parenteral nutrition for newborn and preterm infants as an on-ward preparation.

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.

The effect of UV-protected ethylene vinyl acetate (EVA) bags on the physicochemical stability of pediatric parenteral nutrition admixtures.

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.

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

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 (CaCl2 ) using LO. The purpose of this study was to conduct compatibility testing for neonatal PN solutions containing CaCl2 and CaGlu with cysteine. METHODS: 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. RESULTS: 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. 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 CaCl2 .

Do carnitine and extra trace elements change stability of paediatric parenteral nutrition admixtures?

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.

[Quality control of mixtures for pediatric parenteral nutrition: Validation of sodium and potassium assay method]. / Contrôle qualité des mélanges pour nutrition parentérale pédiatriques : validation de la méthode de dosage du sodium et du potassium.

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.

Complicaciones hidroelectrolíticas e infecciosas en un año de nutrición parenteral en cuidados críticos / Hydroelectrolytic and infectious complications in one year of parenteral nutrition in critical care

Objetivo: La nutrición parenteral consiste en la administración intravenosa de macronutrientes, micronutrientes y electrolitos. Nuestros objetivos fueron evaluar las alteraciones bioquímicas durante los diez primeros días de inicio y cuantificar las bacteriemias relacionadas con el catéter venoso central durante la administración de la nutrición parenteral. Material y métodos: Estudio retrospectivo de incidencia y de prevalencia. Se incluyeron 51 pacientes que iniciaron terapia de soporte nutricional intravenosa en la Unidad de Reanimación. Pretendemos conocer las complicaciones infecciosas de la vía central asociadas a nutrición parenteral, evaluar las complicaciones hidroelectrolíticas más frecuentes de la nutrición parenteral, e identificar puntos mínimos de control en la detección de las alteraciones hidroelectrolíticas. Resultados: Se encontraron variaciones diarias estadísticamente significativas para la glucosa, magnesio, potasio y creatinina, y rozando la significación estadística para la albúmina y el fosfato, ocurriendo las alteraciones entre el segundo y tercer día fundamentalmente. La hipoalbuminemia y la hipocalcemia fueron muy frecuentes. La GGT fue la enzima hepática que se elevó con más frecuencia. La tasa de infección fue de 14,86 por cada 1.000 días de catéter venoso central. Conclusiones: Encontramos variaciones diarias en la glucosa, potasio y magnesio, así como también un descenso de creatinina. Destacamos la frecuencia de hipoalbuminemia, hipocalcemia y de elevación de GGT. Las variaciones más importantes ocurrieron entre el segundo y tercer día, destacando la precocidad de alteración del potasio y el pico de glucemia. La tasa de infección relacionada con el catéter venoso central en los pacientes con nutrición parenteral fue alta

Objective: Parenteral nutrition consists of the intravenous administration of macronutrients, micronutrients and electrolytes. Our objectives were to evaluate the biochemical alterations during the first ten days of initiation and to quantify the bacteremia related to the central venous catheter during the administration of parenteral nutrition. Material and methods: Retrospective study of incidence and prevalence. We included 51 patients who started intravenous nutritional support therapy at Critical Care. We intend to know the infectious complications of the central line associated with parenteral nutrition, to evaluate the most frequent hydroelectrolytic complications of parenteral nutrition, and to identify minimum control points in the detection of hydroelectrolytic alterations. Results: Statistically significant daily variations were found for glucose, magnesium, potassium and creatinine, and bordering on the statistical significance for albumin and phosphate, the alterations occurring between the second and third days fundamentally. Hypoalbuminemia and hypocalcemia were very frequent. GGT was the liver enzyme that increased more frequently. The infection rate was 14.86 per 1,000 days of central venous catheter. Conclusions: We found daily variations in glucose, potassium and magnesium, as well as a decrease in creatinine. We emphasize the frequency of hypoalbuminemia, hypocalcemia and elevation of GGT. The most important variations occurred between the second and third day, highlighting the precocity of potassium alteration and the peak of glycemia. The rate of infection related to the central venous catheter in patients with parenteral nutrition was high

Nutritional Composition Assessment of 3000 Individualized Parenteral Nutrition Bags in a Tertiary Referral Hospital: Current Prescribing Patterns.

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.

Insulin Instability in Parenteral Nutrition Admixtures.

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.

A Risk- and Science-Based Approach to the Acceptance Sampling Plan Inspection of Protein Parenteral Products.

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.

Determinación de fitoesteroles en emulsiones lipídicas para nutrición parenteral / Phytosterol determination in lipid emulsions for parenteral nutrition

Objetivo: La presencia de fitoesteroles en emulsiones lipídicas de origen vegetal se ha relacionado con la aparición de alteraciones de los parámetros de la función hepática. El objetivo es determinar la presencia de fitoesteroles en las emulsiones registradas en el mercado farmacéutico. Método: Se analizaron tres-cuatro lotes no consecutivos de seis marcas distintas de emulsiones lipídicas (Clinoleic(R), Intralipid(R), Lipofundina(R), Lipoplus(R), Omegaven(R) y Smoflipid(R)) y las diferencias en contenido de fitoesteroles totales entre marcas y entre lotes se estudiaron estadísticamente (ANOVA de un factor, aproximación no paramétrica de Kruskal-Wallis y análisis post hoc Scheffé; p < 0,05). Resultados: Se encontró ausencia de fitoesteroles en el preparado Omegaven(R) con aceite de pescado. El contenido más alto de fitoesteroles (422,4 ± 130,5 µg/mL) coincidió con el porcentaje más alto de aceite de soja (Intralipid(R)). En el resto de las emulsiones se detectaron concentraciones de fitoesteroles entre 120 y 210 µg/mL, relacionadas con el contenido de aceite de soja. Se observaron diferencias estadísticamente significativas entre todas las marcas de emulsiones lipídicas (F = 42,97; p = 0,000) y entre lotes no consecutivos. Clinolenic(R) (F = 23,59; p = 0,000); Intralipid(R) (F = 978,25; p = 0,000); Lipofundina(R) TCL/TCM (F = 5,43; p = 0,045); Lipoplus(R) (F = 123,53; p = 0,000),; y Smoflipid(R) (16,78; p = 0,000). Excepto en el caso de la Lipofundina(R) TCL/TCM las diferencias entre lotes fueron marcadas. Conclusiones: Las emulsiones lipídicas registradas en el mercado farmacéutico español contienen cantidades variables de fitoesteroles en función de la marca comercial y el lote. La determinación del contenido de fitoesteroles, actualmente no declarados, permitiría desarrollar estrategias para prevenir o tratar la aparición de estas alteraciones

Objective: The presence of phytosterols in vegetal lipid emulsions has been associated with alterations of liver function tests. Determination of phytosterols content, currently undeclared, would allow the development of strategies to prevent or treat these alterations. Method: 3-4 non-consecutive batches of 6 lipid emulsions from different providers (Clinoleic(TM), Intralipid(TM), Lipofundina(TM), Lipoplus(TM), Omegaven(TM) and Smoflipid(TM)) were analyzed. Differences in total phytosterol assay between providers and batches were statistically studied by a one-way ANOVA and Kruskal-Wallis non-parametric approximation and post hoc Scheffé test (p < 0.05). Results: The absence of phytosterols was confirmed in Omegaven(TM), emulsion based on fish oil. The highest assay of phytosterols (422.4 ± 130.5 µg/mL) has been related with the highest percentage of soya bean oil in Intralipid. In the remaining emulsions, concentrations were from 120 to 210 µg/mL related to the percentage of soya bean oil. Statistically significant differences of phytosterol content in lipid emulsions were observed among different providers (F = 23.59; p = 0.000) as well as among non-consecutive batches. Clinolenic(TM) (F = 23.59; p = 0.000), Intralipid(TM) (F = 978.25; p = 0.000), Lipofundina(TM) TCL/TCM (F = 5.43; p = 0.045), Lipoplus(TM) (F = 123.53; p = 0.000) and Smoflipid(TM) (16.78; p = 0.000). Except for Lipofundina(TM) TCL/TCM, the differences between batches were marked. Conclusions: Lipid emulsions, registered on Spanish pharmaceutical market, contain variable quantities of phytosterols dependent on commercial brand and batch

The presence of inorganic calcium in pediatric parenteral admixtures.

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.

INTRODUCCIÓN: los recién nacidos y los lactantes precisan aportes elevados de calcio y fósforo en soluciones con pequeño volumen lo que aumenta el riesgo de formar precipitados de fosfato cálcico. La principal sal de calcio empleado en nutrición parenteral (NP) es el gluconato cálcico, debido a su perfil de solubilidad con el fosfato. Lamentablemente el gluconato cálcico contiene unas concentraciones elevadas de aluminio mayores que el cloruro cálcico, lo que resulta en riesgo potencial de toxicidad por aluminio en pacientes que reciben NP. En este trabajo se evalúa la estabilidad fisicoquímica de 30 mezclas de NP con sales de calcio inorgánico. MÉTODOS: las mezclas de NP se prepararon en bolsas de acetato de etilenvinilo. En una bolsa unicameral se mezclaron aminoácidos, glucosa, y electrolitos incluyendo una sal de calcio inorgánico y una emulsión lipídica al 20% (SMOFlipid®, Omegaven®o Lipofundin MCT/LCT®). Las mezclas se almacenaron a +4 ° C hasta 8 días tras la elaboración. Se realizó un examen visual, estudio de la distribución del tamaño de los glóbulos (mediante microscopía óptica, difracción por láser y espectroscopia fotónica), análisis de pH y medición del potencial zeta. RESULTADOS: se confirmó la estabilidad fisicoquímica de 29 mezclas de NP que contenían sales de calcio inorgánico. Sólo una de las preparaciones se consideró inválida para su uso clínico debido a la coalescencia de las gotas de grasa. CONCLUSIÓN: a pesar de la presencia de sales de calcio inorgánico, las mezclas de NP pediátrica fueron estables hasta 8 días de almacenamiento. La presencia de múltiples componentes y el riesgo elevados de incompatibilidades hace recomendable el estudio de estabilidad fisicoquímica de cada mezcla antes de su empleo en la clínica.

Evaluating Differences in Aluminum Exposure through Parenteral Nutrition in Neonatal Morbidities.

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.

Determination of Polycyclic Aromatic Hydrocarbons in Commercial Parenteral Formulations and Medications Using High-Performance Liquid Chromatography with Diode Array Detection.

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.

Nitrogenous content in parenteral nutrition: a four-year experience in a general hospital. Critically-ill patient specificity / Contenido nitrogenado de la nutrición parenteral: un estudio de cuatro años en un hospital general. Especificidad en paciente crítico

Introduction: There have been several studies focusing on caloric intake during the last years, while protein content relevance has been underestimated. Some recent evidence has shown that protein deficiency has also an impact on patient outcomes. We have studied the nitrogen (N) content in parenteral nutrition (PN) bags administered to adult patients in a Spanish tertiary level hospital for four years. Material and methods: Patients who received parenteral nutrition in the general ward and Intensive Care Unit (ICU) were recorded. Caloric and protein content were registered and adjusted to weight and length of stay. Data were compared among three group of patients: those in the general ward, those in the ICU and those requiring renal replacement therapy (RRT). The one-factor analysis of variance (ANOVA) test was used after checking data normality and homoscedasticity Results: There was an increase in the mean g N/stay year after year (p < 0.01) from 14 to 15.5 g, with a decrease in non-protein caloric content (p < 0.001) from 111.6 to 101.8 kcal/g N. The range was established from 4.1 to 32.6 g. PN diets with ≥ 18 g N% ranged from 12.8% (2010) to 19.6% (2013). There were significant differences among the groups when comparing the variable g N/stay (p < 0.0001): 13.5 general ward vs 15.9 ICU patients vs 17.6 ICU with RRT, also when referring to adjusted weight. Conclusions: According to most recent recommendations nitrogen has been provided in higher amounts than previously, especially in critical care patients with RRT (AU)

Introducción: algunos estudios recientes sugieren que se ha dado gran importancia al aporte calórico en la nutrición parenteral (NP) del paciente adulto, infraestimando su contenido proteico. Sin embargo, se ha demostrado su relación con los resultados clínicos. Con este objetivo se ha estudiado el contenido en nitrógeno (N) de las NP administradas en un hospital terciario a lo largo de cuatro años. Material y métodos: se recogieron datos de la NP de pacientes hospitalizados en planta, así como en la Unidad de Cuidados Intensivos (UCI). El peso del paciente, su índice de masa corporal (IMC), el contenido en nitrógeno (total y por peso), el aporte calórico no proteico y la duración de la NP fueron algunas de las variables estudiadas. Se compararon en 2013 los aportes en la planta general, en UCI y en aquellos que recibieron algún tipo de terapia renal sustitutiva (TRS). Se utilizó el análisis de varianza (ANOVA) de un factor, previa comprobación de la normalidad y homocedasticidad. Resultados: se ha observado un aumento progresivo en aporte nitrogenado medio diario cada año (p < 0,01) de 14 a 15,05 g, con descenso del contenido calórico no proteico (p < 0,001) de 111,6 a 101,8 kcal /g N. El rango de N en bolsa fue de 4,1 a 32,6 g. Aumentó el porcentaje de bolsas con ≥ 18 g N (12,8 en 2010 vs. 19,6 en 2013). También hubo diferencias entre grupos de pacientes en g N/estancia (p < 0,0001): 13,5 plantas de hospitalización vs. 15,9 UCI vs. 17,6 UCI con TRS, igualmente si referidos a peso ajustado. Conclusiones: En consonancia con las recomendaciones más recientes, el contenido en nitrógenos ha aumentado con los años, en especial en la NP del paciente crítico, siendo aún mayor en los sometidos a TRS (AU)

Evaluación del grado de formación del personal que elabora las nutriciones parenterales en los Servicios de Farmacia / Training degree assessment of staff producing parenteral nutrition in Pharmacy Services

Objetivo: Evaluar el grado de formación del personal que elabora nutrición parenteral en los Servicios de Farmacia. Material y métodos: Se diseñó una encuesta on-line con 17 preguntas en la que se incluyeron los puntos más importantes en la elaboración de nutriciones parenterales. Para el diseño de la encuesta y el análisis posterior se utilizó la aplicación informática Survey monkey®. Resultados: Se obtuvieron un total de 135 respuestas. En el 95% de los Servicios de Farmacia existían normas escritas de elaboración. El 67% contestó que el fosfato se debía añadir cuando se empiezan a añadir los electrolitos y el 34% que no se realizaba la validación de la técnica aséptica de elaboración. En cuanto a la formación, el 19% no la había recibido, considerando necesario recibirla el 99%. Conclusiones: El personal encuestado presenta un grado de formación aceptable, pero son necesarios los cursos de formación que se deben fomentar desde los Servicios de Farmacia (AU)

Objective: To assess the level of expertise of Pharmacy personnel in the manufacturing of total parenteral nutrition. Material and methods: An on-line survey including 17 questions concerning key aspects of TPN manufacturing was designed. Survey monkey software was used to create the survey and to analize its results. Results: 135 answers were received. 95% of the participant Pharmacy services had written standard manufacturing procedures. 67% answered that phosphate salts should be the first electrolite to be additioned into the total parenteral nutrition and 34% affirmed that validation of the aseptic manufacturing technique was not performed. As far as personnel training was concerned, 19% of respondents had not received any specific training, although 99% considered it would be necessary to receive it. Conclusions: The polled personell has an acceptable level of expertise but adequate training courses are still necessary and should be promoted from Pharmacy services (AU)