Parenteral nutrition compatibility and stability: Practical considerations.

Parenteral nutrition (PN) is a complex preparation that contains multiple component products with the associated risk for incompatibilities and diminished stabilities when combined together as an admixture. Significant patient harm can result from prescribing, preparing, and administering PN without confirming compatibility and stability. Incompatibility or instability is rarely obvious to the unaided eye, so safe PN admixture relies on incorporating physicochemical properties of the included components into compatibility and stability decisions. Practices include applying active ingredient concentration limits to reduce risk for incompatibilities and instabilities. The purpose of the current article is to distill the wide-ranging information on PN compatibility and stability into a feasible blueprint that individual healthcare organizations can then use to design and implement practical initiatives. Compatibility and stability considerations can be incorporated into the routine tasks of PN prescribing, order reviewing, preparing, and administering. The focus of this review is on identifying potential physicochemical interactions that can be addressed at each step in the PN use process. Organizations should incorporate compatibility and stability considerations into the routine procedures and practices of all clinicians involved with PN therapy. Those clinicians in healthcare organizations and caregivers in the home should then be in a position to safely provide the appropriate PN admixtures in terms of compatibility and stability.

Stability and compatibility of parenteral nutrition solutions; a review of influencing factors.

Both stability and compatibility of parenteral nutrition solutions (PNS) with drug products are major concerns for clinicians and clinical pharmacists, especially when concurrent administration of PNS with intravenous medications (IVM) is unavoidable. Since the same physicochemical principles apply to both adult's and paediatrics' PNS, concerns about stability and compatibility may still apply to both. However, these concerns are relatively more common in paediatrics and neonatal clinical settings, where limited vascular access can be problematic and the coadministration of PNS and drugs is more common. In neonatal and paediatric populations, there have been few experimental studies and comprehensive evaluations looking at medication compatibility with frequently used PNS. This work is part of a larger research project concerned for compatibility of PNS with commonly used intravenous medication in paediatric and neonates. This paper captures and reviews published data on factors influencing stability and compatibility of parenteral nutrition solutions. This information will help clinicians and clinical pharmacists to understand the principals of the stability and compatibility of PNS, furthermore, it will inform better design of future compatibility studies, as it highlights the complexity of PNS and the multiple factors influencing the stability of PNS, and hence its compatibility with IVM. When preparing, prescribing, and administering the PNS, especially when co-administration with IVM is unavoidable, it is important to take into account the physicochemical properties of the PNS components and IVM as well as administration conditions and environmental factors. These factors should also be considered in the design of the compatibility studies of the PNS with the IVM.

Supplementations of industrial multichamber parenteral nutrition bags in critically ill children: Safety of the practice.

BACKGROUND: Parenteral nutrition (PN) is sometimes required in critically ill children because of contraindication or intolerance to full enteral nutrition. European guidelines recommend favoring multichamber bag PN (MCB PN), when possible, for quality purposes and ease of use. The prescribers may adjust the MCB PN through supplementations to better fulfill patient needs. The objective of this study is to investigate the use and supplementations of MCB PN. METHODS: This observational, single-center, retrospective study was conducted in a pediatric intensive care unit (PICU). We collected prescriptions of MCB PNs and their supplementations added directly into PN bags. A descriptive analysis and a comparison of electrolyte supplementations with the manufacturer's recommendations were undertaken. RESULTS: One hundred thirty-five children (median age 39.2 months [7.0-118.8]) were included, 1449 MCB PNs were administered, and 1652 supplementations were carried out in 736 PN bags. Thirty-two percent of supplementations were vitamins, 32.2% were trace elements, and 35.8% were electrolytes. Around 10% of electrolyte supplementations in PN bags were outside the manufacturer's recommendations. These nonconformities primarily concerned phosphate. CONCLUSION: This study showed the real-world clinical use of MCB PN in the PICU. Proper attention should be paid to septic risks and physicochemical risks to ensure efficient practice and safety of MCB PN use.

A Narrative Review: Analysis of Supplemental Parenteral Nutrition in Adults at the End of Life.

"End of life" is a stage defined by the existence of an irreversible prognosis that ends with a person's death. One of the aspects of interest regarding end of life focuses on parenteral nutrition, which is usually administered in order to avoid malnutrition and associated complications. However, parenteral nutrition can be adapted to specific circumstances and evolve in its functionality through supplementation with certain nutrients that can have a beneficial effect. This narrative review aims to carry out a situation analysis of the role that could be adopted by supplemental parenteral nutrition in attenuating alterations typical of end of life and potential improvement in quality of life.

Addition of Regular Insulin to Ternary Parenteral Nutrition: A Stability Study.

BACKGROUND: Parenteral nutrition (PN) is a complex medium in which added insulin can become unstable. The aim of this study is, therefore, to evaluate the stability of insulin in PN and to identify influencing factors. METHODS: A total of 20 IU/L of regular insulin was added to PN in either glass or Ethylene Vinyl Acetate (EVA) containers. A 24 h stability study was performed via an electrochemiluminescence immunoassay in different media: A ternary PN admixture, separate compartments of the PN bag and a binary admixture. This study was repeated in the absence of zinc, with the addition of serum albumin or tween and with pH adjustment (3.6 or 6.3). Insulin concentration at t time was expressed as a percentage of the initial insulin concentration. Analysis of covariance (ANCOVA) was applied to determine the factors that influence insulin stability. RESULTS: In all PN admixtures, the insulin concentration ratio decreased, stabilising at a 60% and then plateauing after 6 h. At pH 3.6, the ratio was above 90%, while at pH 6.3 it decreased, except in the amino acid solution. ANCOVA (r2 = 0.68, p = 0.01) identified dextrose and pH as significant factors influencing insulin stability. CONCLUSION: A low pH level seems to stabilise insulin in PN admixtures. The influence of dextrose content suggests that insulin glycation may influence stability.

Review of evolution and current status of protein requirements and provision in acute illness and critical care.

Nutrition therapy, by enteral, parenteral, or both routes combined, is a key component of the management of critically ill, surgical, burns, and oncology patients. Established evidence indicates overfeeding (provision of excessive calories) results in increased risk of infection, morbidity, and mortality. This has led to the practice of "permissive underfeeding" of calories; however, this can often lead to inadequate provision of guideline-recommended protein intakes. Acutely ill patients requiring nutritional therapy have high protein requirements, and studies demonstrate that provision of adequate protein can result in reduced mortality and improvement in quality of life. However, a significant challenge to adequate protein delivery is the current lack of concentrated protein solutions. Patients often have fluid administration restrictions and existing protein solutions are frequently not sufficiently concentrated to deliver a patient's protein requirements. This has led to the development of new enteral and parenteral nutrition solutions incorporating higher levels of protein in smaller volumes. This review article summarizes current evidence supporting the role of higher protein intakes, especially during the early phases of nutrition therapy in acute illness, methods for assessing protein requirements, as well as, the currently available high-protein enteral and parenteral nutrition solutions. There is sufficient evidence (albeit limited from true randomized, controlled studies) to indicate that earlier provision of guideline-recommended protein intakes may be key to improving patient outcomes and that nutritional therapy that tailors caloric and protein intake to the patients' needs should be considered a desired standard of care.

Stability Study and Clinical Evaluation of Lipid Injectable Emulsion in Parenteral Nutrition Admixtures Used for Preterm Neonates.

BACKGROUND: Intravenous administration of parenteral nutrition (PN) admixtures containing 4-oil lipid injectable emulsion (ILE) in preterm neonates is usually prohibited because of limited clinical data. The authors evaluated the stability, safety, and efficacy of PN admixtures containing 4-oil ILE, for the first time, in preterm neonates. METHODS: A series of PN admixtures were prepared for consecutive administration in preterm neonates over a period of 15 days. Admixture stability was assessed after 24 hours of storage at 25 and 37 °C via visual inspection and measurement of mean droplet size (MDS). Safety and efficacy of the admixtures in preterm neonates were assessed via serum triglyceride levels and body weight increase measurements, respectively. RESULTS: PN admixtures were stable at 25 °C and had MDS ˂500 nm. After 15 days, there was a significant increase in body weight (P ≤ .0001) and level of serum triglycerides (P ≤ .0001), compared with the level before PN administration. CONCLUSIONS: PN admixtures containing 4-oil ILE were stable at 25 °C and showed instability at 37 °C. Therefore, it is recommended to keep the temperature during administration of PN admixtures at 25 °C. PN admixtures were well tolerated and safe over a period of 8 days while providing a balanced fatty acid supply. Tight monitoring of serum triglyceride level is essential, particularly in neonates of low birth weight and/or young gestational age, to avoid hypertriglyceridemia. Hence, the use of these PN admixtures is expected to be beneficial in terms of being cost-effective and reducing the contamination risks.

Early History of Home Parenteral Nutrition: From Hospital to Home.

Technologic advances in the past century have led to the ability to safely deliver parenteral nutrition (PN) to hospitalized patients. Key breakthroughs included the development of saline and glucose infusions, infusion pumps, macronutrients (lipids, dextrose, and amino acids), and central venous catheters. In the 1960s, centrally delivered PN was performed in short-term hospitalized patients by Lincoln James Lawson (North Staffordshire Royal Infirmatory, United Kingdom) and long-term patients by Stanley Dudrick (University of Pennsylvania, United States). These early studies showed that a system was needed that would allow patients with intestinal failure to be discharged from the hospital and receive home PN (HPN). In the late 1960s and early 1970s, Belding Scribner, Maurice Shils, Khursheed Jeejeebhoy, Marvin Ament, Dudrick, and their teams discharged patients from the hospital who then self-administered HPN. Shortly after these early cases of HPN, multidisciplinary centers were established first in North America, and later in Europe, to manage these complex cases. The current article describes the patients treated by these early HPN pioneers, in addition to subsequent case series reported by them and others.

Technology in Parenteral Nutrition Compounding.

Technology is constantly being used in novel ways, and its use in the practice of medicine is no exception. Examples of this include computer physician order entry, barcode-medication scanning, electronic health records (EHRs), and bedside patient charts, to name a few. Compounding parenteral nutrition has been included in this technological revolution, with improvements such as barcode-assisted medication preparation systems and EHR-to-compounder interfaces. Along with some of these electronic advancements come the inevitable improvements and challenges, which are explored in this article.

Long-Term Use of Mixed-Oil Lipid Emulsion in Adult Home Parenteral Nutrition Patients: A Case Series.

BACKGROUND: Despite providing significant benefits, home parenteral nutrition (HPN) can be associated with complications such as infections, intestinal failure-associated liver disease, and metabolic abnormalities. Soybean oil (SO)-based intravenous lipid emulsion (ILE) has been noted to contribute to some of these complications, leading to the development of alternative sources of ILE. Mixed-oil (MO) ILE has recently been approved for use in adults with short-term studies revealing a benefit over SO ILE. Currently there is a paucity of data regarding long-term use in the HPN population. METHODS: The current study reports our experience with MO ILE in 9 HPN patients. RESULTS: A total of 9 patients (3 women and 6 men) with average age of 48.1 ± 15.1 years and a median HPN use of 9.9 years (9.0 months-30.7 years) were transitioned from SO ILE to MO ILE as a result of intolerance. The 9 patients tolerated MO ILE well for 140.7 ± 29.7 days. The percentage of calories provided through ILE increased from 7.6 ± 6.5% to 18.4 ± 8.2% (P = .003), whereas the dextrose decreased from 66.9 ± 8.4% to 56.9 ± 5.5% (P = .0007). Although statistical significance was not reached, there was a trend toward improvement in alkaline phosphatase from 138.0 (52-884) to 106 (47-512; P = .09). CONCLUSION: MO ILE was well tolerated in this small cohort and led to improvement in the macronutrient composition of HPN while providing a trend toward improvement in liver studies. These results are promising; however, additional randomized control trials are needed to delineate the true benefit.

Physicochemical Stability and Sterility of Standard Parenteral Nutrition Solutions and Simulated Y-Site Admixtures for Neonates.

BACKGROUND: Parenteral nutrition (PN) is frequently needed in neonatal intensive care. The use of standard PN has emerged as an easy-to-prescribe approach that allows one to have on-site, ready-to-use PN. The aim of this study was to test the physicochemical stability and sterility of 2 specific PN solutions as well as simulate Y-site compatibility with lipid injectable emulsions (ILE). METHODS: Our study considered 2 standard ILE-free PN solutions according to neonatal weight. These solutions were prepared in duplicate and stored at 4°C. The following physicochemical parameters were tested: visual alterations, turbidity, pH, osmolarity, and calcium concentration. Sterility was assessed by means of agar blood culture and glucose concentration determination. In addition, we assessed the stability of simulated Y-site admixtures. For each standard ILE-free PN solution, 2 3-in-1 PN admixtures were designed, considering extreme values of fluid requirements (50 and 150 ml/kg/d) and a fat supply of 2 g/kg/24 h. The physicochemical parameters tested were phase separation and fat mean droplet size distribution. RESULTS: No alterations were detected by visual inspection. Calcium concentrations, turbidity, pH, and osmolarity values remained stable in all the determinations. All agar blood cultures were negative and glucose concentration was constant over time. Physical stability of simulated Y-site admixtures was considered acceptable as mean droplet size distribution remained below 500 nm in all the emulsions. CONCLUSION: The 2 tested standard ILE-free PN solutions for neonates are physicochemically stable and sterile for 31 days under refrigeration (4°C). These solutions are also stable in case of Y-site administration with ILE at the conditions tested.

Overview of Home Parenteral Nutrition: An Update.

The trend in modern medicine is to transition care from the hospital to home or other nonacute settings as soon as possible. Increasingly, nutrition support professionals are being asked to help facilitate discharge and/or manage patients who require prolonged intravenous fluid and/or nutrition after having been stabilized during a hospitalization. This updated tutorial reviews many of the concepts and challenges that must be considered for successful care that helps to focus on the patients and their quality of life.

Efficacy, Safety, and Preparation of Standardized Parenteral Nutrition Regimens: Three-Chamber Bags vs Compounded Monobags-A Prospective, Multicenter, Randomized, Single-Blind Clinical Trial.

BACKGROUND: Parenteral nutrition (PN) covering the need for carbohydrates, amino acids, and lipids can either be compounded from single nutrients or purchased as an industrially manufactured ready-to-use regimen. This study compares a commercially available 3-chamber bag (study group) with a conventionally compounded monobag regarding nutrition efficacy, safety, and regimen preparation time. MATERIALS AND METHODS: This prospective, randomized, single-blind study was conducted at 5 Chinese hospitals from October 2010-October 2011. Postsurgical patients requiring PN for at least 6 days were randomly assigned to receive the study or control regimen. Plasma concentrations of prealbumin and C-reactive protein (CRP), regimen preparation time, length of hospital stay (LOS), 30-day mortality, safety laboratory parameters, and adverse events (AEs) were recorded. RESULTS: In total, 240 patients (121 vs 119 in study and control groups) participated in this study. Changes in prealbumin concentrations during nutrition support (ΔPrealb(StudyGroup) = 2.65 mg/dL, P < .001 vs ΔPrealb(ControlGroup) = 0.27 mg/dL, P = .606) and CRP values were comparable. Regimen preparation time was significantly reduced in the study group by the use of 3-chamber bags (t(StudyGroup) = 4.90 ± 4.41 minutes vs t(ControlGroup) = 12.13 ± 5.62 minutes, P < .001). No differences were detected for LOS, 30-day mortality, safety laboratory parameters, and postoperative AEs (37 vs 38 in study and control groups). CONCLUSION: The PN regimen provided by the 3-chamber bag was comparable to the compounded regimen and safe in use. Time savings during regimen preparation indicates that use of 3-chamber bags simplifies the process of regimen preparation.

Immunoassay quantification of human insulin added to ternary parenteral nutrition containers: comparison of two methods.

Adding insulin directly into infusion bags seems to be a useful method for controlling hyperglycemia in patients under ternary parenteral nutrition (TPN). Its efficacy is assessed by glycemic monitoring but few data are available on insulin stability in this situation. Among the various methods for quantifying insulin levels in human serum, the immunoassay ones seemed potentially appropriate for a TPN admixture containing high lipid concentrations. We sought to identify and validate which of two immunoassay methods was the better to quantify human insulin and consequently be adapted to studying its stability in a TPN admixture. Two immunoassay methods to quantify recombinant human insulin were assessed in industrial TPN: an immunoradiometric assay (IRMA) and an immunoelectrochemiluminometric assay (IECMA). Validation trials for both methods were based on the accuracy profile method. Interference with immunometric assays due to the high lipidic content of TPN was eliminated through an improved preparation protocol using a bovine serum albumin (BSA) diluted in phosphate buffer saline (PBS). The relative total error of IECMA varied from 1.74 to 4.52% while it varied from -0.32 to 8.37% with IRMA. Only IECMA provided an accuracy profile with a 95% confidence interval of calculated-tolerance limits falling between the chosen acceptance limits (i.e., total error ≤±10%). IECMA combined with a BSA dilution is a simple and semi-automatic method that provides an accurate quantification of human insulin in a TPN admixture without any interference from lipids.

A Product Review of Alternative Oil-Based Intravenous Fat Emulsions.

Soybean oil-based intravenous fat emulsions have long been used as the primary product for delivery of lipid-based calories in parenteral nutrition formulations in the United States. Proinflammatory properties of these products may be related with poor clinical outcomes and have led investigators to develop newer generations of intravenous fat emulsions. These alternative formulations are derivatives of medium-chain triglycerides, olive oil, and fish oil in hopes to reduce the inflammatory response and potentially produce a clinically beneficial anti-inflammatory response. Although surrogate markers support this reduction in inflammatory response, clinical data and outcomes are still limited but potentially promising in the literature. This product review provides a general overview of the alternative-generation intravenous fat emulsion products and the literature supporting the potential transition to such products.

Repackaging of Intravenous Fat Emulsions: A Clinical Conundrum.

To accommodate small fluid volumes, repackaging of intravenous fat emulsions (IVFEs) is frequently performed in institutions providing parenteral nutrition to neonates and smaller pediatric patients. However, some consider this an unsafe practice. Concerns for potential administration errors leading to an overdose of IVFEs are weighed against the potential for microbial contamination from the repackaging process. The clinician providing pediatric nutrition support should tailor repackaging practices to ensure patient safety and quality. This discussion aims to describe the strengths and limitations surrounding IVFE repackaging to provide guidance regarding the practice.

Parenteral Nutrition Basics for the Clinician Caring for the Adult Patient.

Parenteral nutrition (PN) is a life-sustaining therapy providing nutrients to individuals with impaired intestinal tract function and enteral access challenges. It is one of the most complex prescriptions written routinely in the hospital and home care settings. This article is to aid the nutrition support clinician in the safe provision of PN, including selecting appropriate patients for PN, vascular access, development of a PN admixture, appropriate therapy monitoring, recognition of preparation options, and awareness of preparation and stability concerns.

Rehidratación en el paciente pediátrico / Rehydration in pediatric patients / Rehidratação em pacientes pediátricos

La deshidratación en el paciente pediátrico es una de las causas de morbimortalidad más importantes en países en vía de desarrollo; por tanto, es imprescindible el correcto manejo de esta patología con el fin de disminuir los desenlaces fatales y prevenibles de la enfermedad. Se realizó una revisión de la literatura con respecto a la fisiología, la fisiopatología, la clínica, el mecanismo de acción, las indicaciones y las contraindicaciones de las sales de rehidratación oral y las soluciones de administración endovenosa, con el fin de brindar ciertas pautas y recomendaciones basadas en la evidencia actual, a todos los profesionales de la salud, que a diario enfrentan este tipo de patología. La investigación demostró que las sales de rehidratación oral siguen siendo el Gold Estándar en el tratamiento de la deshidratación leve a moderada en pacientes con indicaciones de uso y que las soluciones de administración endovenosa son de vital apoyo en aquel grupo de pacientes con deshidratación grave con intolerancia a la vía oral, shock, íleo paralitico, ciertas patologías quirúrgicas y con contraindicaciones de terapia con sales de rehidratación oral.

Dehydration in pediatric patients is one of the most common causes of mobility and mortality in developing countries; therefore, the right management of this disease is essential in order to reduce fatal and preventable disease outcomes. A review of the literature was made with respect to the physiology, pathophysiology, clinical manifestations, mechanism of action, indications and contraindications of oral rehydration salts and intravenous solutions, in order to provide some recommendations based on current evidence, to all physicians, who daily work on this kind of pathology. The investigation showed that ORS remains the Gold Standard in the treatment of mild to moderate dehydration in patients with indications and intravenous solutions, are of vital support in the group of patients with severe dehydration, oral intolerant, shock, paralytic ileus, certain surgical pathologies and therapy contraindications ORS.

A desidratação em pacientes pediátricos é uma das causas mais comuns de mobilidade e mortalidade nos países em desenvolvimento; Portanto, o manejo correto desta doença é essencial para reduzir os resultados fatais e evitáveis da doença. Realizou-se revisão da literatura em relação à fisiologia, fisiopatologia, manifestações clínicas, mecanismo de ação, indicações e contra-indicações dos sais de reidratação oral e soluções intravenosas, a fim de fornecer algumas recomendações baseadas em evidências atuais a todos os médicos, que diariamente Trabalho sobre esse tipo de patologia. A investigação mostrou que a SRO permanece como padrão-ouro no tratamento da desidratação leve a moderada em pacientes com indicações e soluções intravenosas, são de suporte vital no grupo de pacientes com desidratação grave, intolerância oral, choque, íleo paralítico, certas patologias cirúrgicas e Terapia contra-indicações ORS.

Discrepancies Between Prescribed and Actual Pediatric Home Parenteral Nutrition Solutions.

BACKGROUND: Home parenteral nutrition (HPN) is increasingly prescribed for pediatric patients with complex medical conditions. Commercial vendors are widely available to compound HPN. The aim of this study was to determine the frequency of discrepancies between written HPN prescriptions and commercially compounded solutions, as well as to record the associated severity of harm from discrepancies. METHODS: From January to April 2013, 2 clinical pharmacists independently and prospectively reconciled HPN compounding records with electronic prescriptions (gold standard) during all routine ambulatory encounters to a multidisciplinary HPN program. Types, severity, and causes of discrepancies were recorded. RESULTS: Sixty-one unique patients were identified for inclusion during 117 visits. HPN solutions were compounded at 13 unique vendors across 14 states. Of all 100 compounding records, 46 (46%) contained at least 1 discrepancy, with a total of 60 discrepancies identified, affecting 34 of 61 (56%) patients. There was at least 1 discrepancy in solutions originating from 10 of 13 (77%) home infusion companies. Discrepancies were classified as Medication Error Reporting and Prevention levels C (n = 37) and D (n = 23; ie, all reaching patient but not causing harm). CONCLUSIONS: We found an alarmingly high rate of preparation discrepancies in a cohort of pediatric patients receiving HPN. Routine reconciliation of HPN compounds with intended prescriptions may be critical for ambulatory patients receiving this high-risk therapy. While home infusion commercial vendors provide an indispensable function, discrepancies and errors with potential for harm may be more common than previously appreciated.