Parenteral Nutrition Drug Shortages: A Single-Center Experience With Rapid Process Change.

Disruptions in the medication supply chain and consequent drug product shortages, including shortages of parenteral products used for parenteral nutrition (PN) compounding, have become an increasingly common occurrence. The amino acid solution shortage that resulted from the devastating impact of Hurricanes Maria and Irma on manufacturing facilities in Puerto Rico in 2017 necessitated a rapid, coordinated shift from use of compounded PN to commercial multichamber-bag PN (MCB-PN) at our hospitals. We describe our experience operationalizing this intervention via a framework that may be adapted for addressing other drug product shortages to promote rapid yet safe use of therapeutic alternatives.

A Review of the Parenteral Nutrition Supply Service in an Irish Neonatal Unit

Background Neonatal Intensive Care (NICU) patients have individual nutritional requirements often requiring Patient Specific Parenteral Nutrition (PSPN). From October 2015, the national PSPN compounding service availability changed from 7 days per week service to 5 days per week (i.e. no weekend and limited bank holiday ordering available). The aim of this study was to examine the introduction of a 5 day only PSPN supply on neonatal patient parenteral nutrition availability in a tertiary NICU. Methods We performed a prospective assessment of the provision of a 5 day rather than 7 day ordering of PSPN over a one month period (June 2017). Results Fifteen neonatal patients received a cumulative 89 days of PN during June 2017. 10 (66%) patients received PSPN during this time period. There was same day availability of PSPN in 62 of 89 days of PN (69%). Conclusion Thorough education and training will help prescribers to make appropriate PSPN ordering decisions. Improvements to available stock bags may reduce the amount of PSPN that is required but a 7 day PSPN ordering service would improve efficient provision of clinically indicated PSPN to premature infants in NICU in Ireland.

Drug Shortages: Effect on Parenteral Nutrition Therapy.

Drug shortages continue to be a threat to the health and welfare of numerous patients in the United States. For patients who depend on parenteral nutrition (PN) for survival, these shortages pose an even greater threat. Almost 75% of active drug shortages are sterile injectables, which includes PN components. Providing PN therapy is particularly challenging for clinicians because this is a complex medication and may contain 40 or more individual ingredients, of which multiple components may simultaneously be in limited supply. The availability of PN components must be considered during every step of the PN use process from ordering the PN prescription to administering this therapy to a patient. Alterations to a standardized process can lead to medication errors that can adversely affect patient outcomes and consume healthcare resources.

Impact of the Nationwide Intravenous Selenium Product Shortage on the Development of Selenium Deficiency in Infants Dependent on Long-Term Parenteral Nutrition.

BACKGROUND: For patients dependent on parenteral nutrition (PN), selenium must be supplemented intravenously. A nationwide intravenous selenium shortage began in April 2011. The impact of this shortage on PN-dependent infants was evaluated by examining the provision of selenium, development of biochemical deficiency, and costs associated with the shortage. MATERIALS AND METHODS: This single-center, retrospective study included PN-dependent infants aged ≤1 year who weighed ≤30 kg, received PN for ≥1 month, and had ≥1 serum selenium measurement. The primary outcome was the incidence of biochemical selenium deficiency. Secondary outcomes included severity of biochemical deficiency, clinical manifestations, costs, and relationship between serum selenium levels and selenium dose. RESULTS: The average selenium dose decreased 2-fold during the shortage (2.1 ± 1.2 µg/kg/d; range, 0.2-4.6 µg/kg/d) versus the nonshortage period (3.8 ± 1 µg/kg/d; range, 2.4-6 µg/kg/d; P < .001). A linear relationship between serum selenium concentration and selenium dose was observed (r(2) = 0.42), with a dose of 6 µg/kg/d expected to result in normal serum levels in most cases. Similar proportions of patients developed biochemical deficiency in both groups: shortage period, 59.1%; nonshortage, 66.7%; P = .13. The severity of biochemical deficiency was similar between groups. A significant increase in incremental cost during the shortage was observed. CONCLUSION: This is the first study examining the impact of the intravenous selenium shortage on PN-dependent infants. Both groups exhibited similarly high incidences of biochemical selenium deficiency, suggesting higher empiric doses may benefit this population. However, ongoing shortages limit the ability to provide supplementation.

Zinc Deficiency With Dermatitis in a Parenteral Nutrition-Dependent Patient Due to National Shortage of Trace Minerals.

The shortages of intravenous drugs remains critical, with sterile injectables accounting for 80% of the approximately 300 shortages. The impact is being felt in patients dependent on parenteral nutrition (PN), and severe deficiencies are becoming more commonplace. We report here a man who developed severe zinc deficiency, manifesting as a painful desquamative rash, due to an inability to obtain multi-trace element additives for his PN.

Validación de la conservación de la cadena de frío durante la distribución de mezclas de nutrición parenteral / Validation of cold chain during distribution of parenteral nutrition

Objetivo: el presente estudio tiene la finalidad de demostrar la aptitud del proceso empleado para acondicionar las mezclas de nutrición parenteral extemporáneas para su distribución, considerando el objetivo de conservar la cadena de frío durante el traslado hasta que llega al paciente, necesario para asegurar la estabilidad, efectividad y seguridad de estas mezclas. Método: validación concurrente; diseño e implementación de un protocolo de evaluación del proceso de acondicionamiento y distribución de MNPE elaboradas por un laboratorio farmacéutico. Ejecución de test, según criterios de aceptación predefinidos. Se efectúa en dos oportunidades, en verano y en las rutas que requieren un tiempo de traslado más prolongado. Evaluación de la conservación de la temperatura mediante supervisión de los valores de temperatura interna de cada tipo de empaquetado, registrados por equipos data loggers calibrados. Resultados: los diferentes test cumplen con los criterios preestablecidos. Los valores obtenidos permiten asegurar el mantenimiento de la cadena de frío durante un tiempo superior al traslado hasta los puntos más distantes. Conclusiones: este estudio permite mostrar la aptitud del proceso de acondicionamiento de MNPE para su distribución, manteniendo la cadena de frío durante todo el traslado desde el Laboratorio farmacéutico hasta el paciente. Considerando que la rotura de la cadena de frío puede ocasionar alteraciones de la compatibilidad y estabilidad de las nutriciones parenterales, así como fallas en el soporte nutricional, este estudio contribuye a la seguridad del paciente, una de las dimensiones relevantes de la calidad de la atención de la salud (AU)

Objective: this study aims to demonstrate the suitability of the process used to condition the extemporaneous mixtures of parenteral nutrition for distribution, considering the objective of preserving the cold chain during transport until it reaches the patient, necessary to ensure stability, effectiveness and safety of these mixtures. Method: concurrent validation, design and implementation of a protocol for evaluating the process of packaging and distribution of MNPE developed by a pharmaceutical laboratory. Running tests, according to predefined acceptance criteria. It is performed twice, in summer and on routes that require longer transfer time. Evaluation of conservation of temperature by monitoring the internal temperature values of each type of packaging, recorded by data loggers calibrated equipment. Results: the different tests meet the established criteria. The collected data ensure the maintenance of the cold chain for longer than the transfer time to the most distant points. Conclusions: this study establishes the suitability of the processes to maintaining the cold chain for transfer from the laboratory to the patient pharmacist. Whereas the breaking of cold chain can cause changes of compatibility and stability of parenteral nutrition and failures nutritional support, this study contributes to patient safety, one of the relevant dimensions of quality of care the health (AU)

Finding new solutions in pediatric parenteral admixtures: how to improve quality and to deal with shortages.

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.

INTRODUCCIÓN: La nutrición parenteral pediátrica permite un crecimiento normal incluso en lactantes pretérmino. Sin embargo, estos niños requieren una nutrición parenteral a medida y la formulación de tal nutrición puede suponer un reto por el riesgo de inestabilidad y el desabastecimiento. OBJETIVO: Se crearon mezclas parenterales prototípicas utilizando diferentes sales de calcio (orgánicas e inorgánicas) y diferentes emulsiones lipídicas probando su estabilidad. Se investigaron 36 mezclas parenterales que contenían dos tipos de sales de calcio (cloruro o gluconolactobionato) y diferentes emulsiones lipídicas (SMOFlipid® o Lipofundin MCT/LCT®). MÉTODOS: Se prepararon unas pre-mezclas en bolsas bicompartimentales mientras que las emulsiones lipídicas se colocaron de forma separada en la segunda cámara. Las pre-mezclas se almacenaron hasta 21 días a +4º C. Se combinaron los contenidos de ambas cámaras en t = 0 o después de 21 días de almacenamiento. El análisis físico de las mezclas completadas (inspección visual, observación microscópica, medición del pH y determinación de la distribución por tamaño de las gotitas lipídicas) se realizó a los 21 días de almacenamiento. También se estudió la estabilidad de las emulsiones lipídicas almacenadas en bolsas comerciales de acetato de etilen vinilo (AEV) durante 42 días. RESULTADOS: Independientemente del tiempo de almacenamiento de las pre-mezclas y el tipo de sal de calcio y de las diferentes emulsiones lipídicas de entre el total de 36 mezclas parenterales, sólo en una se vieron signos de desestabilización tras la preparación y una fue inestable cuando se almacenó más de 14 días. El resto de las formulaciones se consideraron estables durante el estudio. Todas las emulsiones lipídicas comerciales investigadas fueron estables físicamente en las bolsas de AEV, incluso cuando se almacenaron a temperatura ambiente. CONCLUSIÓN: El estudio mostró que es posible almacenar pre-mezclas en bolsas de AEV durante 21 días a 4° C. También se vio que el NAC (número de agregación crítica) y el CaxP (los productos de la multiplicación de las concentraciones de los iones calcio y fósforo) no deberían utilizarse como indicadores fiables de la estabilidad física de las mezclas. No se observó ninguna influencia del tipo de sal de calcio sobre la estabilidad de las mezclas.

Finding new solutions in pediatric parenteral admixtures; how to improve quality and to deal with shortages / Encontrando nuevas soluciones en las mezclas parenterales pediatricas; ¿cómo mejorar la calidad y gestionar el desabastecimiento?

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 (AU)

Introducción: La nutrición parenteral pediátrica permite un crecimiento normal incluso en lactantes pretérmino. Sin embargo, estos niños requieren una nutrición parenteral a medida y la formulación de tal nutrición puede suponer un reto por el riesgo de inestabilidad y el desabastecimiento. Objetivo: Se crearon mezclas parenterales prototípicas utilizando diferentes sales de calcio (orgánicas e inorgánicas) y diferentes emulsiones lipídicas probando su estabilidad. Se investigaron 36 mezclas parenterales que contenían dos tipos de sales de calcio (cloruro o gluconolactobionato) y diferentes emulsiones lipídicas (SMOFlipid® o Lipofundin MCT/LCT®). Métodos: Se prepararon unas pre-mezclas en bolsas bicompartimentales mientras que las emulsiones lipídicas se colocaron de forma separada en la segunda cámara. Las pre-mezclas se almacenaron hasta 21 días a +4º C. Se combinaron los contenidos de ambas cámaras en t = 0 o después de 21 días de almacenamiento. El análisis físico de las mezclas completadas (inspección visual, observación microscópica, medición del pH y determinación de la distribución por tamaño de las gotitas lipídicas) se realizó a los 21 días de almacenamiento. También se estudió la estabilidad de las emulsiones lipídicas almacenadas en bolsas comerciales de acetato de etilen vinilo (AEV) durante 42 días. Resultados: Independientemente del tiempo de almacenamiento de las pre-mezclas y el tipo de sal de calcio y de las diferentes emulsiones lipídicas de entre el total de 36 mezclas parenterales, sólo en una se vieron signos de desestabilización tras la preparación y una fue inestable cuando se almacenó más de 14 días. El resto de las formulaciones se consideraron estables durante el estudio. Todas las emulsiones lipídicas comerciales investigadas fueron estables físicamente en las bolsas de AEV, incluso cuando se almacenaron a temperatura ambiente. Conclusión: El estudio mostró que es posible almacenar pre-mezclas en bolsas de AEV durante 21 días a 4° C. También se vio que el NAC (número de agregación crítica) y el CaxP (los productos de la multiplicación de las concentraciones de los iones calcio y fósforo) no deberían utilizarse como indicadores fiables de la estabilidad física de las mezclas. No se observó ninguna influencia del tipo de sal de calcio sobre la estabilidad de las mezclas (AU)

Selenium deficiency in pediatric patients with intestinal failure as a consequence of drug shortage.

BACKGROUND: Parenteral nutrition (PN) is a lifesaving therapy for children with intestinal failure and can now be used chronically without the life-threatening complications of the past. Adequate intravenous trace element supplementation is required as part of a complete nutrition prescription. According to the U.S. Food and Drug Administration (FDA), the number of drug shortages, including sterile injectable agents used as PN components, has increased since 2010. Selenious acid as an individual additive was recently unavailable at our institution for 9 months due to a national shortage. MATERIALS AND METHODS: To assess the impact of the selenious acid shortage, we retrospectively compiled data from existing clinical records for eligible patients. We included children with intestinal failure on full PN support who were older than 1 year at the onset of the selenium shortage. Whole-blood selenium concentrations prior to the selenious acid shortage were compared with concentrations drawn during the shortage. RESULTS: Five patients with intestinal failure and complete PN dependence were identified, and all 5 patients had normal serum selenium concentrations prior to the shortage. All 5 patients developed severe biochemical selenium deficiency in direct correlation with the shortage of selenium. No morbidity associated with selenium deficiency was observed. Selenium concentrations recovered after selenium supplementation was reinstituted. CONCLUSION: A national selenious acid shortage was associated with biochemical selenium deficiency in a cohort of children with intestinal failure. Despite very low selenium concentrations, none of our patients exhibited clinical signs of deficiency.

Anemia and leukopenia in a long-term parenteral nutrition patient during a shortage of parenteral trace element products in the United States.

Recently, drug shortages in the United States have affected multiple components of the parenteral nutrition (PN) solution. A 62-year-old patient with systemic sclerosis who was dependent on home PN due to intestinal dysmotility developed anemia and leukopenia approximately 4 months after parenteral copper was withheld from her PN solution due to drug shortages. The patient was not able to tolerate a sufficient amount of oral multivitamins with trace elements due to severe dysphagia. Her serum copper and ceruloplasmin concentrations were undetectable, confirming the diagnosis of severe copper deficiency. The hematological abnormalities promptly resolved with copper supplementation. This report emphasizes the importance of close monitoring for nutrient deficiencies during drug shortages and supplementing with oral or enteral nutrition when feasible, particularly in high-risk patients such as those with intestinal malabsorption or short bowel syndrome who are dependent on long-term PN.

Parenteral nutrition additive shortages: the short-term, long-term and potential epigenetic implications in premature and hospitalized infants.

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages and rationing have been associated with adverse outcomes, such as lactic acidosis and Wernicke encephalopathy from thiamine deficiency or pulmonary and skeletal development concerns related to inadequate stores of Vitamin A and D. In this review, we will discuss the current parenteral shortages and the possible impact on a population of very low birth weight infants. This review will also present a case study of a neonate who was impacted by these current shortages.