Parenteral Nutrition Admixtures Research Articles

Electron Microscopy for the Stability Assessment of Parenteral Nutrition Admixtures: Focus on Precipitation.

(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.

Shortages of clinical nutritional components and management strategies

Parenteral nutrition (PN) solution is a medication of high concern due to its intricate drug utilization procedure. It has been reported that since 2010, nearly every component involved in the preparation of PN admixtures has experienced a shortage at least once. Shortages may lead to therapy delays in hospitals, clinics and other health-related facilities or reductions in quality, prompting healthcare providers to recommend alternative treatments, potentially leading to medication errors, negatively influencing patient outcomes, and consume healthcare assets. The causes of medication shortages are diverse and encompass unidentified factors (44%), manufacturing complications (36%), supply and demand imbalances (8%), discontinued product lines (8%), insufficient access to raw materials (4%), and natural disasters. The duration for the resolution of these shortages was inconsistent, with certain product shortages that were resolved experiencing a recurrence, while others persisted for several months to years. The pharmacy department can take the lead in efficiently managing drug shortages by guaranteeing that its institution possesses the essential infrastructure and a clearly outlined management strategy well in advance of any shortages arising. During periods of shortages, it is extremely important to limit the use of nutritional products to patients with valid indications and those with nonfunctional gastrointestinal systems. Effective management of drug shortages, including PN components, necessitates a comprehensive plan and the involvement of an interprofessional team. This team should contribute to the development of the plan and be ready to implement it swiftly in case of a shortage or outage. Once the shortage of PN components is deemed resolved, all rationing and conservation strategies should be halted, as these measures are meant to be employed exclusively during shortages. Once the PN component shortage has been resolved, it is crucial to resume providing the full dosage of PN components to all patients in need of PN therapy.

Global availability of parenteral nutrition: Pre- and post-COVID-19 pandemic surveys

ObjectiveParenteral nutrition represents a therapeutic option for patients with type 3 intestinal failure. If used exclusively, parenteral nutrition has to be complete to provide all essential nutrients. The aim was to assess the availability of parenteral nutrition in all parts of the world, to better comprehend the global situation, and to prepare an action plan to increase access to parenteral nutrition. MethodsAn international survey using an electronic questionnaire was conducted in August 2019 and repeated in May 2022. An electronic questionnaire was sent to 52 members or affiliates of the International Clinical Nutrition Section of the American Society for Parenteral and Enteral Nutrition. Questions addressed the availability of parenteral nutrition admixtures and their components, reimbursement, and prescribing pre- and post-COVID-19 pandemic. All participating countries were categorized by their economic status. ResultsThirty-six country representatives responded, answering all questions. Parenteral nutrition was available in all countries (100%), but in four countries (11.1%) three-chamber bags were the only option, and in six countries a multibottle system was still used. Liver-sparing amino acids were available in 18 (50%), kidney-sparing in eight (22.2%), and electrolyte-free in 11 (30.5%) countries (30.5%). In most countries (n = 28; 79.4%), fat-soluble and water-soluble vitamins were available. Trace elements solutions were unavailable in four (11.1%) countries. Parenteral nutrition was reimbursed in most countries (n = 33; 91.6%). No significant problems due to the coronavirus pandemic were reported. ConclusionsDespite the apparent high availability of parenteral nutrition worldwide, there are some factors that may have a substantial effect on the quality of parenteral nutrition admixtures. These shortages create an environment of inequality.

Y-Site Compatibility Studies of Parenteral Nutrition and Other Intravenous Medications in Neonatal and Pediatric Patients: A Review of the Literature Evidence.

Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an "A" grade (very high quality), and the grades "B", "C", and "D" were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients.

Stability of individualized neonatal parenteral nutrition admixtures with fish oil and high calcium content.

the stability of total parenteral nutrition admixtures for neonates (TPNAn) has been questioned in relation to the interaction between calcium and fish oil emulsions. the aim of this study was to check the stability (particle size < 1 µm) of different individualized TPNAn prepared with fish-oil emulsion and containing calcium at concentrations ranging from 10 to 20 mmol/L. admixtures analyzed: twelve different formulations with SMOFlipid® 20 % (conserved for 24 h and for 96 h), three formulations with Lipoplus® 20 % (conserved for 96 h) and three formulations with SMOFlipid® 20 % with Multi-12K1® Pediatric (conserved for 96 h). Two bags were compounded for each formulation and conservation period. Measurements on each admixture bag: particle standardized diameter by laser diffraction technique and pH by a calibrated pH-meter. Data analysis with mixed linear regression models. maximum particle size was < 0.8 µm for all investigated admixtures. Lipid concentration of 5 g/L and sodium and potassium concentration of 100 mmol/L slightly increased the proportion of particles > 0.6 µm. Ninety six hours storage also increased the percentage of particles > 0.6 µm (+0.143 ± 0.07; p = 0.038) but did not influence other parameters. No association with calcium composition was observed. Amino acid content was inversely correlated with pH (-0.83; p < 0.0001). the studied individualized parenteral nutrition admixtures for newborns that contain fish oil emulsions and meet cation requirements are stable for at least 96 hours.

Compatibility of nanoparticulate iv iron with all-in-one parenteral nutrition admixtures tested by ICP-MS

Compatibility of nanoparticulate iv iron with all-in-one parenteral nutrition admixtures tested by ICP-MS

Safety in parenteral nutrition compounding.

Parenteral nutrition (PN) compounding is a complex process that requires knowledge and training to ensure the safety and efficacy of this form of nutrition support therapy. Unfortunately, errors and lack of adherence to safe PN compounding recommendations and sterile compounding requirements have resulted in patient injury and death. These lapses in the safe provision of PN have been the result of various factors, including a lack of understanding of PN compatibility, stability, and sterility requirements, as well as drug product shortages and order entry errors. This review will describe the current challenges with the education and training regarding PN compounding, compatibility and stability of PN admixtures, simultaneous administration of nonnutrient medications with PN admixtures, and specific challenges with special populations such as neonates, pediatrics, and those receiving home care.

Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies

PurposeAminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids. MethodsGentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure. ResultsGM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage. ConclusionIn conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Antiemetic Drugs Compatibility Evaluation with Paediatric Parenteral Nutrition Admixtures.

Chemotherapy-induced nausea and vomiting are defined as the most common of side effects of treatment and, at the same time, are very difficult to accept for patients', frequently causing changes in the therapy regimen, significantly reducing its effectiveness. Thus, an antiemetic prophylactic is essential to the provision of such a therapy for the patient. Pharmacotherapy often includes various drugs, including antiemetics, with the administration of such drugs by injection through two separate catheters being the preferred method. However, the co-administration of drugs and parenteral nutrition admixtures (PNAs) requires the consideration of compatibility, stability and potential negative interactions. To meet the purposes of clinical pharmacy, a compatibility test of ondansetron, dexamethasone and hydrocortisone with paediatric PNAs was conducted. PNAs differ in the composition of amino acid source (Primene® or Aminoplasmal Paed® 10%) and the type of injectable lipid emulsion (Lipidem® 200 mg/mL, Clinoleic® 20%, SMOFlipid® 200 mg/mL, Intralipid® 20%). An in vitro evaluation was performed in a static way as a simulated co-administration through a Y-site. The drug PNA ratios were determined based on the extreme infusion rates contained in the characteristics of medicinal products. All calculations were performed for a hypothetical patient aged 7 years weighing 24 kg. As a result of this study, it can be concluded that all tested PNAs showed the required stability in the range of parameters such as pH, osmolality, turbidity, zeta potential, MDD and homogeneity. The co-administration of antiemetic drugs does not adversely affect lipid emulsion stability. This combination was consistently compatible during the evaluation period.

Stability of furosemide and torasemide in parenteral nutrition admixture

Furosemide and torasemide (loop diuretics) are used to treat hypertension or pulmonary edema. They are often administered in the parenteral route. In critically ill patients, there is a problem of a limited number of venous accesses, which complicates the polytherapy. Drugs of unknown compatibility must be administered separately, and the problem increases in patients receiving parenteral nutrition. Lipid emulsions have been introduced into clinical practice as a high-calorie, non-glucose source of energy for parenteral administration, but they can also be used as lipophilic drug carriers. In this paper, the parenteral nutrition admixture (PNA) Nutriflex Lipid special was used as a drug carrier for furosemide and torasemide. For this purpose, drug stability tests (HPLC method) were carried out in various light and temperature conditions, imitating clinical conditions, and the parameters of the lipid emulsion (pH, zeta potential, the size of the emulsion droplets and polpolydispersity) were tested. Furosemide and torasemide added to Nutriflex Lipid special did not cause significant changes in the physicochemical properties of PNA. Changes in pH and MDD were within acceptable limits. Both drugs when added to Nutriflex Lipid special were degraded, dependent on the storage conditions and the chemical structure.

Y-Site Compatibility Studies of Ketoprofen with Parenteral Nutrition Admixtures for Central and Peripheral Administration.

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.

One-chamber and two-chamber parenteral nutrition admixtures for pediatric and adult patients: An evaluation of physico-chemical stability at room and cold temperature

ObjectivesThe aim of this study was to evaluate the physico-chemical stability of compounded total parenteral nutrition admixtures through peroxidation assay and ultraviolet-visible spectroscopy, high-performance liquid chromatography analysis, nuclear magnetic resonance spectrometry, pH meter, and dynamic light scattering. MethodsThe present study considered parenteral nutrition (PN) admixtures for pediatric and adult patients. The admixtures were characterized by a high content of vitamins and trace elements. They were prepared in one- or two-chamber bags in the hospital pharmacy using an automatic compounding system in a sterile room with laminar airflow at different temperature conditions and light exposure. The experiment setup comprised fat emulsions, lipid-free PN solutions, and single-chamber bags before and after adding vitamins and trace elements. The stability at room temperature (+25°C) and cold temperature (+2–8°C) was assessed by various means. ResultsTwo-compartment admixtures, single-chamber bags, and all-in-one PN supplemented with vitamins and trace elements are stable up until 35, 9, and 7 d, respectively, when protected from light and stored at +2 to 8°C. Also, the supplemented single-chamber PN was found to be stable up to 48 h when stored at +25°C with light exposure. ConclusionsThe results obtained will help improve PN management at the compounding center and in hospital wards, because they allow for the extension of the validity time frame provided so far by the different formulations and, therefore, therapy scheduling over several days.

Pitfalls of iron supplementation in parenteral nutrition admixtures for children with intestinal failure.

Pediatric patients with intestinal failure are at increased risk for iron deficiency. Supplementation is not routinely included in parenteral nutrition solutions. There is currently limited research related to the safety of iron supplementation in parenteral nutrition and for intravenous forms used in patients with intestinal failure. Current American Society for Parenteral and Enteral Nutrition and ESPGHAN guidelines promote the use of enteral iron, acknowledging the risks of using iron supplementation within parenteral nutrition admixtures. We review a patient case and the current available literature related to iron in parenteral nutrition. Five major concerns are identified: peroxidation reactions, incompatibility, hypersensitivity, infection risk, and iron overload. We propose an argument against the preferential use of iron supplementation within parenteral nutrition in children with intestinal failure when enteral supplementation or intermittent parenteral infusion may be sufficient.

Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation.

Parenteral-nutrition (PN)-induced hyperglycemia increases morbidity and mortality and must be treated with insulin. Unfortunately, the addition of insulin to a ternary PN admixture leads to a rapid decrease in insulin content. Our study’s objective was to determine the mechanistic basis of insulin’s disappearance. The literature data suggested the presence of a glycation reaction; we therefore validated an LC-MS/MS assay for insulin and glycated insulin. In a 24-h stability study, 20 IU/L of insulin was added to a binary PN admixture at pH 3.6 or 6.3. When the samples were diluted before analysis with a near-neutral diluent, insulin was fully stable at pH 3.6, while a loss of around 50% was observed at pH 6.3. Its disappearance was shown to be inversely correlated with the appearance of monoglycated insulin (probably a Schiff base adduct). Monoglycated insulin might also undergo a back-reaction to form insulin after acidic dilution. Furthermore, a second monoglycated insulin species appeared in the PN admixture after more than 24 h at high temperature (40 °C) and a high insulin concentration (1000 IU/L). It was stable at acidic pH and might be an Amadori product. The impact of insulin glycation under non-forced conditions on insulin’s bioactivity requires further investigation.

Co-administration of drugs with parenteral nutrition in the neonatal intensive care unit—physical compatibility between three components

There is a lack of compatibility data for intravenous therapy to neonatal intensive care unit (NICU) patients, and the purpose of this study was to contribute with documented physical compatibility data to ensure safe co-administration. We selected Numeta G13E, the 3-in-1 parenteral nutrition (PN) used at our NICU, together with the frequently used drugs morphine, dopamine and cefotaxime in two- but also three-component combinations. Incompatibility may lead to particle formation (precipitation) and oil-droplet growth (emulsion destabilisation), both which are undesirable and pose a safety risk to already unstable patients. We assessed potential particle formation of three mixing ratios for each combination (always including 1 + 1 ratio) using light obscuration, turbidity and pH measurements combined with visual inspection by focused Tyndall beam. Potential droplet-growth and emulsion destabilisation was assessed by estimating PFAT5 from droplet size measurements and counts, mean droplet diameter and polydispersity index from dynamic light scattering, and pH measurements. Mixed samples were always compared to unmixed controls to capture changes as a result of mixing and samples were analysed directly after mixing and after 4 h to simulate long contact time. None of the samples showed any sign of precipitation, neither in the drug-drug nor in the two- or three-component mixture with PN. Neither did we detect any form of emulsion destabilisation.Conclusion: Dopamine, morphine and cefotaxime were found to be compatible with NumetaG13E, and it is safe to co-administer these drugs together with this PN in NICU patients.What is Known:• The need for co-administration of drugs and complex PN admixtures occurs frequently in NICU due to limited venous access.• Available compatibility data are scarce and for combinations of more than two components non-existent.What is New:• Here we report physical compatibility data of two- as well as three-component combinations of frequently used NICU drugs and a 3-in-1 PN admixture.• Co-administration of Numeta G13E with dopamine and morphine, but also with morphine and cefotaxime is safe in NICU.

Management of Hyperglycemia in Hospitalized Patients Receiving Parenteral Nutrition.

Almost half of inpatients on parenteral nutrition experience hyperglycemia, which increases the risk of complications and mortality. The blood glucose target for hospitalized patients on parenteral nutrition is 7.8 to 10.0 mmol/L (140 to 180 mg/dL). For patients with diabetes, the same parenteral nutrition formulae as for patients without diabetes can be used, as long as blood glucose levels can be adequately controlled using insulin. Insulin can be delivered via the subcutaneous or intravenous route or, alternatively, added to parenteral nutrition admixtures. Combining parenteral with enteral and oral nutrition can improve glycemic control in patients with sufficient endogenous insulin stores. Intravenous insulin infusion is the preferred route of insulin delivery in critical care as doses can be rapidly adjusted to altered requirements. For stable patients, insulin can be added directly to the parenteral nutrition bag. If parenteral nutrition is infused continuously over 24 hours, the subcutaneous injection of a long-acting insulin combined with correctional bolus insulin may be adequate. The aim of this review is to give an overview of the management of parenteral nutrition-associated hyperglycemia in inpatients with diabetes.

Sodium Valproate Incompatibility with Parenteral Nutrition Admixtures-A Risk to Patient Safety: An In Vitro Evaluation Study.

Epilepsy is defined as a group of concerning problems related to the nervous system; its defining feature is a predisposition to epileptic seizures. The frequency of seizures in intensive care units (ICU) ranges from 3.3% to 34%, and ICU antiepileptic treatment is routine practice. The administration of drugs through the same infusion line is not recommended but is common clinical practice, especially in ICU. Incompatibilities between parenteral drugs and between drugs and parenteral nutrition admixtures (PNAs) are common medical errors and pose risks to patient safety. The co-administration of drugs must always be confirmed and clearly defined. The simultaneous infusion of sodium valproate (VPA, drug used to treat seizures and epilepsy) with parenteral PNAs has not yet been studied. During the experiment reported in this study, a visual control, pH, osmolality, zeta potential, particle size, polydispersity index, and turbidity were measured. The conducted research shows that the lipid emulsion composition has a significant influence on drug–PN (drug–parenteral nutrition) compatibility. The acceptance criteria were met only for PNs containing omega-3-acid-triglycerides (Omegaflex special and peri). The second fraction of particles above 1000 nm was observed for most of the tested PNAs (Lipoflex special, Lipoflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E), which disqualifies their simultaneous administration with VPA.

Sources of unintentional manganese delivery in neonatal parenteral nutrition.

Manganese (Mn) neurotoxicity is a concern in neonates receiving parenteral nutrition (PN). Prior studies have identified Mn contamination of PN ingredients as a source of daily Mn exposure from PN. This study was conducted to determine which neonatal PN ingredients are sources of this unintentional Mn delivery. Mn concentration was measured in different lot numbers of individual PN ingredients using inductively coupled plasma-mass spectrometry. PN admixtures were then prepared using standard doses of the tested individual ingredients, and admixture Mn concentration was measured. Magnesium sulfate and calcium gluconate are the major contributors to hidden unintentional Mn exposure in neonatal PN. Maximum measured Mn concentrations in these two ingredients were 443 and 46.8 mcg/L, respectively. Sodium phosphate and potassium phosphate were the next highest at 40 and 24 mcg/L, respectively. Other ingredients contained a trivial or no measurable quantity of Mn. PN admixture Mn content was 16%-30% higher than predicted values based on individual ingredient Mn content. If infused at 150 ml/kg/day, a standard neonatal PN admixture with no added Mn is capable of unintentionally delivering up to 0.9 mcg/kg/day Mn. Neonatal PN without any added Mn provides close to the American Society for Parenteral and Enteral Nutrition (ASPEN)-recommended Mn dosage of 1 mcg/kg/day. This supports the potential utility of a Mn-omission approach to trace element provision in neonatal PN. Further studies are needed to test such an approach and to evaluate the clinical significance of unintended Mn delivery in neonates receiving PN.

ASHP Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition Admixtures.

ASHP Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition Admixtures.

Parenteral nutrition compatibility and stability: A comprehensive review.

Several guidance documents support best practices across the stages of the parenteral nutrition (PN) use process to optimize patient safety. The critical step of PN order verification and review by the pharmacist requires a contextual assessment of the compatibility and stability implications of the ordered PN prescription. This article will provide working definitions, describe PN component characteristics, and present a wide-ranging representation of compatibility and stability concerns that need to be considered prior to preparing a PN admixture. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.