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All4Nutra.com > Supported Nutrients > Lipids & Essential Fatty Acids > The Modern Approach to Total Parenteral Nutrition: Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction

News Innovations Lipids & Essential Fatty Acids
| 12. March 2025

The Modern Approach to Total Parenteral Nutrition: Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction

The Modern Approach to Total Parenteral Nutrition Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction

The Modern Approach to Total Parenteral Nutrition Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction

Abstract

With advancements in medical technology, biochemistry, and clinical practices, the modern approach to total parenteral nutrition (TPN) has been focused on precision, safety, and the optimization of metabolic and nutritional parameters based on the patient’s needs. In the last decade, TPN mixtures have been transitioning from a lifesaving intervention for patients unable to receive enteral nutrition to a highly specialized therapy aimed at improving clinical outcomes, reducing complications, and personalizing care. Total parenteral nutrition has attracted great interest, and its adaptation to the patient’s needs is a topic of interest in the scientific community. However, there are problems related to shortages in the supply of the concentrates required to balance TPN mixtures and to infections linked to the venous access devices that are necessary for administering nutrition. Adjusting the TPN composition to meet specific patient needs requires specialist knowledge, as the ingredients available on the market differ in terms of excipients and this may increase the risk of physicochemical incompatibilities, particularly the destabilization of the lipid fraction. It is common clinical practice to inject drugs into the parenteral nutrition bag, and hence there is a high demand for confirmation of the compatibility of a given drug with the TPN composition. However, methods used in clinical practice still differ from the modern solutions proposed in scientific research. In order to ensure patient safety with the use of advanced therapy, continuous education and monitoring of the latest scientific research related to TPN is required. The integration of artificial intelligence (AI) into clinical nutrition represents a paradigm shift in the management of total parenteral nutrition (TPN). As TPN transitions from a standardized, one-size-fits-all approach to a highly personalized therapy, we must examine the challenges and future directions of AI-driven TPN to provide a comprehensive analysis of its impact on clinical practice.

1. Introduction

The lipid fraction has a crucial role in balancing parenteral nutrition. It is also the most fragile part of TPN formulations when it comes to physicochemical stability and drug incompatibilities. For many years, vegetable oil derivatives, especially soybean oil emulsions, were used as the single source of lipids [1,2,3]. There is growing evidence that lipid emulsions based only on soybean oil should be avoided in some clinical states. In recent years, soybean oil has become just a part of the complex lipid emulsions used, and different mixtures of lipid emulsions have become available. The most popular ones combine olive oil, fish oil, and medium-chain triglycerides (MCTs) together in different ratios. One of the available alternatives to pure soybean oil is SMOFlipid® Fresenius Kabi AB, Uppsala, Sweden, a lipid emulsion that contains 30% soybean oil, 30% MCT, 25% olive oil, and 15% fish oil. The ClinOleic® Baxter, Warsaw, Poland lipid emulsion is composed of 80% olive oil and 20% soybean oil. The use of different lipid emulsions in TPN requires caution in the selection of additives for a given patient.
The destabilization of lipid emulsions usually occurs in stages, only some of which are reversible. The migration of lipid droplets toward the surface of the emulsion is called creaming and can be reversed by mixing the contents of the TPN bag.

Another reversible stage is flocculation, the formation of clusters of small lipid droplets without aggregation. The irreversible process of lipid droplets combining into aggregates, called coalescence, leads to an increase in lipid droplet size and separation of the emulsion. The complete separation of the lipid phase from the water phase disqualifies the emulsion from clinical use and is an irreversible process. These destabilization processes are initiated by changes in pH, high concentrations of electrolytes, the presence of free fatty acids, temperature fluctuations, and interactions with newly injected components. Elevated temperatures promote the coalescence and creaming of lipid droplets, while prolonged storage increases the risk of triglyceride hydrolysis to free fatty acids. The occurrence of these processes is not always visible to the naked eye, which is why it is so crucial to conduct physicochemical analyses of all modified compositions. Due to the variety of excipients in the preparations used in the mixtures (mainly solubilizers and emulsifiers), physicochemical analyses should be repeated for each composition and when changing the component manufacturer. Unfortunately, clinical practices differ between hospital wards due to different local protocols and the availability of components.

One of the major challenges in parenteral nutrition is the addition of various substances directly to TPN bags. Although this practice is sometimes used to reduce the number of punctures and infusion lines, it carries a significant risk of destabilization of the lipid mixture and pharmacological interactions. The addition of polyvalent ions (especially calcium and magnesium ions) and trace elements can significantly affect the stability of a lipid emulsion. High concentrations of these ions neutralize the zeta potential, which reduces the electrostatic repulsion between lipid droplets and promotes their fusion. Lipid emulsions are extremely sensitive to pH changes. The optimum pH for most lipid emulsions is 6.0–8.0. The release of free fatty acids causes reductions in the pH, which destabilizes the emulsion by lowering the zeta potential and increasing flocculation. Drugs added directly to the mixture affect the pH and may cause the formation of precipitates with the ions present in the mixture. Not every hospital has a nutritional team consisting of a physician, pharmacist, dietitian, and nurse, as well as its own nutrition laboratory. For this reason, all-in-one nutrition bags, which are activated immediately before administration to the patient, are popular. The compositions of ready-made mixtures are also modified by adding drugs to the activated bag, sometimes injected through a port without maintaining aseptic conditions. The key recommendations from ESPEN (European Society for Clinical Nutrition and Metabolism) and ASPEN (American Society for Parenteral and Enteral Nutrition) clearly advise against adding drugs without prior compatibility testing [4,5,6,7]. An alternative is to use separate infusion lines for drug administration and regularly monitoring TPN stability parameters such as the pH, lipid droplet size, and zeta potential.

Download the full article as PDF here:
The Modern Approach to Total Parenteral Nutrition: Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction

or read it here

Sobol, Ż.; Chiczewski, R.; Wątróbska-Świetlikowska, D. The Modern Approach to Total Parenteral Nutrition: Multidirectional Therapy Perspectives with a Focus on the Physicochemical Stability of the Lipid Fraction. Nutrients 2025, 17, 846.
https://doi.org/10.3390/nu17050846

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