Influence of the type of amino acids in the formation of precipitates of copper and sulphur in parenteral nutrition / Influencia del tipo de aminoácidos en la formación de precipitados de cobre y azufre en nutrición parenteral

Objective: we found a black precipitate during the infusion of a parenteral nutrition without lipids. The objective of this study is to check the composition of the precipitate and the influence of the type of amino acids in its formation. Methods: four PN bags were prepared with the following composition: 1 l of amino acids solution, 150 g glucose, 60 mEq potassium, 217 mEq chloride, 105 mEq sodium, 15 mEq magnesium, 15 mEq calcium, 18.63 mmol phosphorus and trace elements (Addamel(R)). Each bag was prepared using a different type of amino acids solution with different amount of cysteine per litre: Tauramin(R) 10% (0.5 g/l), Primene(R) 10% (1.89 g/l), Tauramin(R) 12.6% (0.62 g/l) or Synthamin(R) 10% (0 g/l). Tauramin(R) 10% and Primene(R) 10% were packaged in glass containers whereas Tauramin(R) 12.6% and Synthamin(R) 10%, in plastic. The contents of each bag were filtered using Pall NEO96E 0.2 micron filters. A 2.25% area of each filter was observed by scanning electron microscopy at 100x magnification. The analysis by energy dispersive spectroscopy (EDS) was performed at 1,000x magnification. Results: in the Primene(R) 10% and Tauramin(R) 10% filters, a greater amount of precipitate was observed than with Tauramin(R) 12.6% and Synthamin(R) 10%. The percentage of copper and sulphur in each area of the filters studied was, respectively, 22.9% and 11.5% (Primene(R) 10%), 19.3% and 9.6% (Tauramin(R) 10%), 3.7% and 0% (Tauramin(R) 12.6%), 2.5% y 0% (Synthamin(R) 10%). Conclusions: the observed precipitate contains copper and sulphur. Precipitate formation occurs in high cysteine content amino acids solutions packaged in glass containers. It is important to use filters in the administration of PN to ensure that this type of precipitates are retained and do not pass to the patient. Key words

Objetivo: durante la infusión de una nutrición parenteral (NP) sin lípidos se observó un precipitado negro en el filtro. El objetivo del estudio es comprobar la composición del precipitado y la influencia del tipo de aminoácidos en su formación. Métodos: se prepararon cuatro bolsas de NP con 1.000 ml de solución de aminoácidos, 150 g glucosa, 60 mEq potasio, 217 mEq cloruro, 105 mEq sodio, 15 mEq magnesio, 15 mEq calcio, 18,63 mmol fósforo y oligoelementos (Addamel(R)). Se utilizaron distintos tipos de aminoácidos con concentraciones de cisteína diferentes: Tauramin(R) 10% (0,5 g/l), Primene(R) 10% (1,89 g/l), Tauramin(R) 12,6% (0,62 g/l) o Synthamin(R) 17 (0 g/l). Tauramin(R) 10% y Primene(R) 10% estaban envasados en vidrio y Tauramin(R) 12,6% y Synthamin(R) 17, en plástico. El contenido de cada bolsa se filtró utilizando filtros Pall NEO96E de 0,2 micras. Se estudió un área de 2,25% de cada filtro mediante microscopía electrónica de barrido a 100 aumentos. El análisis mediante espectroscopia de dispersión de energía (EDS) se realizó a 1.000 aumentos. Resultados: en los filtros con Primene(R) 10% y Tauramin(R) 10%, se observó mayor precipitación que con Tauramin(R) 12,6% y Synthamin(R) 10%. El porcentaje de cobre y azufre en cada área de los filtros estudiados fue 22,9% y 11,5% (Primene(R) 10%), 19,3% y 9,6% (Tauramin(R) 10%), 3,7% y 0% (Tauramin 12,6%), 2,5% y 0% (Synthamin 10%). Conclusiones: el precipitado observado contiene cobre y azufre. La formación de precipitados se produce con soluciones de aminoácidos envasadas en vidrio, con gran cantidad de cisteína. Es importante usar filtros en la administración de NP para garantizar que los precipitados se retengan y no se pasen al paciente

Influence of the type of amino acids in the formation of precipitates of copper and sulphur in parenteral nutrition.

INTRODUCTION: Objective: we found a black precipitate during the infusion of a parenteral nutrition without lipids. The objective of this study is to check the composition of the precipitate and the influence of the type of amino acids in its formation. Methods: four PN bags were prepared with the following composition: 1 l of amino acids solution, 150 g glucose, 60 mEq potassium, 217 mEq chloride, 105 mEq sodium, 15 mEq magnesium, 15 mEq calcium, 18.63 mmol phosphorus and trace elements (Addamel®). Each bag was prepared using a different type of amino acids solution with different amount of cysteine per litre: Tauramin® 10% (0.5 g/l), Primene® 10% (1.89 g/l), Tauramin® 12.6% (0.62 g/l) or Synthamin® 10% (0 g/l). Tauramin® 10% and Primene® 10% were packaged in glass containers whereas Tauramin® 12.6% and Synthamin® 10%, in plastic. The contents of each bag were filtered using Pall NEO96E 0.2 micron filters. A 2.25% area of each filter was observed by scanning electron microscopy at 100x magnification. The analysis by energy dispersive spectroscopy (EDS) was performed at 1,000x magnification. Results: in the Primene® 10% and Tauramin® 10% filters, a greater amount of precipitate was observed than with Tauramin® 12.6% and Synthamin® 10%. The percentage of copper and sulphur in each area of the filters studied was, respectively, 22.9% and 11.5% (Primene® 10%), 19.3% and 9.6% (Tauramin® 10%), 3.7% and 0% (Tauramin® 12.6%), 2.5% y 0% (Synthamin® 10%). Conclusions: the observed precipitate contains copper and sulphur. Precipitate formation occurs in high cysteine content amino acids solutions packaged in glass containers. It is important to use filters in the administration of PN to ensure that this type of precipitates are retained and do not pass to the patient. Key words.

INTRODUCCIÓN: Objetivo: durante la infusión de una nutrición parenteral (NP) sin lípidos se observó un precipitado negro en el filtro. El objetivo del estudio es comprobar la composición del precipitado y la influencia del tipo de aminoácidos en su formación. Métodos: se prepararon cuatro bolsas de NP con 1.000 ml de solución de aminoácidos, 150 g glucosa, 60 mEq potasio, 217 mEq cloruro, 105 mEq sodio, 15 mEq magnesio, 15 mEq calcio, 18,63 mmol fósforo y oligoelementos (Addamel®). Se utilizaron distintos tipos de aminoácidos con concentraciones de cisteína diferentes: Tauramin® 10% (0,5 g/l), Primene® 10% (1,89 g/l), Tauramin® 12,6% (0,62 g/l) o Synthamin® 17 (0 g/l). Tauramin® 10% y Primene® 10% estaban envasados en vidrio y Tauramin® 12,6% y Synthamin® 17, en plástico. El contenido de cada bolsa se filtró utilizando filtros Pall NEO96E de 0,2 micras. Se estudió un área de 2,25% de cada filtro mediante microscopía electrónica de barrido a 100 aumentos. El análisis mediante espectroscopia de dispersión de energía (EDS) se realizó a 1.000 aumentos. Resultados: en los filtros con Primene® 10% y Tauramin® 10%, se observó mayor precipitación que con Tauramin® 12,6% y Synthamin® 10%. El porcentaje de cobre y azufre en cada área de los filtros estudiados fue 22,9% y 11,5% (Primene® 10%), 19,3% y 9,6% (Tauramin® 10%), 3,7% y 0% (Tauramin 12,6%), 2,5% y 0% (Synthamin 10%). Conclusiones: el precipitado observado contiene cobre y azufre. La formación de precipitados se produce con soluciones de aminoácidos envasadas en vidrio, con gran cantidad de cisteína. Es importante usar filtros en la administración de NP para garantizar que los precipitados se retengan y no se pasen al paciente.

[Precipitation limits in pediatric parenteral nutritions with organic sources of calcium and phosphate]. / Límites de precipitación en nutriciones parenterales pediátricas con fuentes de calcio y fosfato orgánicas.

OBJECTIVE: to determine if precipitation processes occur in parenteral nutrition solutions (PNs) with calcium gluconate and sodium glycerophosphate in the precipitation threshold limits of the Spanish SENPE/SEGHNP/SEFH 2008 consensus document of PN preparation. METHODS: seven PNs with different composition were prepared in triplicate: five 100 ml PNs with different concentrations of amino acids, calcium and phosphorus similar to consensus document maximum concentrations for precipitation, and two control PNs: one without calcium and phosphorus and other with high calcium and phosphorus content and low concentration of amino acids. All PNs did not contain lipids to allow correct detection of precipitates. The no lipid PNs were stored at room temperature for 20 hours, and at 35 °C for four hours. Subsequently, they filtered through a 0.2 µm filter, which was observed by electron microscopy. Because a large amount of not expected precipitates was observed, complementary studies were carried out. RESULTS: precipitates were observed in all PNs except in the control solution without calcium and phosphorus; many of them were greater than 10 µm. However, according to our studies, these crystals were produced after filtration and calcium was found in their composition, but not phosphorus. Particles from the preparation of parenteral nutrition were also observed. CONCLUSIONS: in our study we did not find calcium phosphate precipitates in the limits included in the consensus document SENPE/SEGHNP/ SEFH. However, it is possible that micro precipitates with calcium are formed. It is important to filter PNs prior to their administration.

OBJETIVO: conocer si hay precipitación en nutriciones parenterales (NP) con gluconato cálcico y glicerofosfato sódico en las cantidades límites del documento de consenso español de preparación de nutrición parenteral SENPE/SEGHNP/SEFH 2008. MÉTODOS: se prepararon por triplicado siete NP: cinco de 100 ml con concentraciones de aminoácidos, calcio y fósforo similares a las concentracionesmáximas de precipitación del documento consenso SENPE/SEGHNP/SEFH y dos controles, uno sin calcio y fósforo y otro con alto contenido de calcio y fósforo y baja concentración de aminoácidos. Las NP no contenían lípidos. Las NP se almacenaron 20 horas a temperatura ambiente y cuatro horas a 35 °C, y se filtraron con un filtro de 0,2 micras. Estos filtros se transportaron y observaron parcialmente por microscopía electrónica. Los cristales observados se analizaron por espectrometría por dispersión de rayos X a 1.000 aumentos. Al observarse gran cantidad de precipitados, que no se correspondían a los estudios publicados, se realizaron estudios complementarios para conocer su origen. RESULTADOS: en todos los casos, a excepción del control sin calcio y fósforo, se observaron precipitados. Sin embargo, estos cristales, según nuestros estudios, se produjeron después de la filtración y en su composición está el calcio, pero no el fósforo. También se observaron partículas provenientes de la preparación de nutrición parenteral. CONCLUSIONES: en nuestro estudio no encontramos precipitados de fosfato cálcico en los límites recogidos en el documento consenso SENPE/SEGHNP/SEFH. Sin embargo, es posible que se formen microprecipitados con calcio en su composición. Es importante fi ltrar las NP previamente a su administración.

Límites de precipitación en nutriciones parenterales pediátricas con fuentes de calcio y fosfato orgánicas / Precipitation limits in pediatric parenteral nutritions with organic sources of calcium and phosphate

Objetivo: conocer si hay precipitación en nutriciones parenterales (NP) con gluconato cálcico y glicerofosfato sódico en las cantidades límites del documento de consenso español de preparación de nutrición parenteral SENPE/SEGHNP/SEFH 2008.Métodos: se prepararon por triplicado siete NP: cinco de 100 ml con concentraciones de aminoácidos, calcio y fósforo similares a las concentraciones máximas de precipitación del documento consenso SENPE/SEGHNP/SEFH y dos controles, uno sin calcio y fósforo y otro con alto contenido de calcio y fósforo y baja concentración de aminoácidos. Las NP no contenían lípidos. Las NP se almacenaron 20 horas a temperatura ambiente y cuatro horas a 35 °C, y se filtraron con un filtro de 0,2 micras. Estos filtros se transportaron y observaron parcialmente por microscopía electrónica. Los cristales observados se analizaron por espectrometría por dispersión de rayos X a 1.000 aumentos. Al observarse gran cantidad de precipitados, que no se correspondían a los estudios publicados, se realizaron estudios complementarios para conocer su origen. Resultados: en todos los casos, a excepción del control sin calcio y fósforo, se observaron precipitados. Sin embargo, estos cristales, según nuestros estudios, se produjeron después de la filtración y en su composición está el calcio, pero no el fósforo. También se observaron partículas provenientes de la preparación de nutrición parenteral. Conclusiones: en nuestro estudio no encontramos precipitados de fosfato cálcico en los límites recogidos en el documento consenso SENPE/SEGHNP/SEFH. Sin embargo, es posible que se formen microprecipitados con calcio en su composición. Es importante fi ltrar las NP previamente a su administración

Objective: to determine if precipitation processes occur in parenteral nutrition solutions (PNs) with calcium gluconate and sodium glycerophosphate in the precipitation threshold limits of the Spanish SENPE/SEGHNP/SEFH 2008 consensus document of PN preparation. Methods: seven PNs with different composition were prepared in triplicate: fi ve 100 ml PNs with different concentrations of amino acids, calcium and phosphorus similar to consensus document maximum concentrations for precipitation, and two control PNs: one without calcium and phosphorus and other with high calcium and phosphorus content and low concentration of amino acids. All PNs did not contain lipids to allow correct detection of precipitates. The no lipid PNs were stored at room temperature for 20 hours, and at 35 °C for four hours. Subsequently, they filtered through a 0.2 μm filter, which was observed by electron microscopy. Because a large amount of not expected precipitates was observed, complementary studies were carried out. Results: precipitates were observed in all PNs except in the control solution without calcium and phosphorus; many of them were greater than 10 μm. However, according to our studies, these crystals were produced after filtration and calcium was found in their composition, but not phosphorus. Particles from the preparation of parenteral nutrition were also observed. Conclusions: in our study we did not fi nd calcium phosphate precipitates in the limits included in the consensus document SENPE/SEGHNP/SEFH. However, it is possible that micro precipitates with calcium are formed. It is important to fi lter PNs prior to their administration

Modelling attrition and nonparticipation in a longitudinal study of prostate cancer.

BACKGROUND: Attrition occurs when a participant fails to respond to one or more study waves. The accumulation of attrition over several waves can lower the sample size and power and create a final sample that could differ in characteristics than those who drop out. The main reason to conduct a longitudinal study is to analyze repeated measures; research subjects who drop out cannot be replaced easily. Our group recently investigated factors affecting nonparticipation (refusal) in the first wave of a population-based study of prostate cancer. In this study we assess factors affecting attrition in the second wave of the same study. We compare factors affecting nonparticipation in the second wave to the ones affecting nonparticipation in the first wave. METHODS: Information available on participants in the first wave was used to model attrition. Different sources of attrition were investigated separately. The overall and race-stratified factors affecting attrition were assessed. Kaplan-Meier survival curve estimates were calculated to assess the impact of follow-up time on participation. RESULTS: High cancer aggressiveness was the main predictor of attrition due to death or frailty. Higher Charlson Comorbidity Index increased the odds of attrition due to death or frailty only in African Americans (AAs). Young age at diagnosis for AAs and low income for European Americans (EAs) were predictors for attrition due to lost to follow-up. High cancer aggressiveness for AAs, low income for EAs, and lower patient provider communication scores for EAs were predictors for attrition due to refusal. These predictors of nonparticipation were not the same as those in wave 1. For short follow-up time, the participation probability of EAs was higher than that of AAs. CONCLUSIONS: Predictors of attrition can vary depending on the attrition source. Examining overall attrition (combining all sources of attrition under one category) instead of distinguishing among its different sources should be avoided. The factors affecting attrition in one wave can be different in a later wave and should be studied separately.