Emulsions parenteral nutrition

When normal enteral feeding in not possible or is inadequate to meet an individual s nutritional needs, intravenous (IV) nutritional therapy or total parenteral nutrition (TPN) is required. Products used to meet the IV nutritional requirements of the patient include protein substrates (amino acids), energy substrates (dextrose and fat emulsions), fluids, electrolytes, and trace minerals (see the Summary Drug Table Electrolytes). 

S Harnisch, RH Muller. Adsorption kinetics of plasma proteins on oil-in-water emulsions for parenteral nutrition. Eur J Pharm Biopharm 49(l) 41-46, 2000. 

Aik Phos, alkaline phosphatase ALT, alanine aminotransferase (SCPT) AST, aspartate aminotransferase (SGOT) Bili, bilirubin EFAD, essential fatty acid deficiency IVFE, intravenous fat emulsion PN, parenteral nutrition. 

The fat emulsion used to solubilise propofol is similar to Intralipid, used for parenteral nutrition. Its disadvantages include (1) being an excellent culture medium if bacterially contaminated and (2) presenting the patient with a... 

Lipid emulsions are essential components of parenteral nutrition. However, due to the amount of polyunsaturated fatty acids (PUFA), it is possible that chemical degradation occurs, forming hydroperoxides. 

Lipid peroxides are also able to react with other components of parenteral nutrition admixtures (trace elements), causing a drop in pH with the subsequent potential for physical-chemical instability [29]. Table 11 shows the peroxide value and the pH drop in a pure lipid emulsion and a lipid-containing AlO admixture stored in EVA bags under different conditions of temperature and light exposure in the presence and absence of trace elements. 

FIGURE 7 Influence of a lipid emulsion and daylight on peroxide levels in freshly prepared solutions of parenteral nutrition containing multivitamins (PN + MVI and PN + Lipid + MVI). (PN = parenteral nutrition MVI = multi vitamin preparation.) The data represent the mean SEM,n = 3 the variations are not depicted because of their small size relative to the symbols. The peroxide content rose significantly over time (P < 0.001), and exposure to daylight had a significant effect on peroxide generation (P < 0.001) [33]. 

Steger, P. J. K., and Mtihlebach, S. F. (2000), Lipid peroxidatoin of intravenous lipid emulsions and all-in-one admixtures in total parenteral nutrition bags The influence of trace elements, J. Parenteral Enteral Nutr., 24, 37M1. 

Popinska, K., Kierkus, I, Lyszkowska, M., Socha, I, Pietraszek, E., Kmiotek, W., and Ksiazky, J. (1999), Aluminum contamination of parenteral nutrition additives, amino acid solutions, and lipid emulsions, Nutrition, 15, 683-686. 

Injectable lipid emulsions are used to provide parenteral nutrition and their use can be traced back to the 1920s. However, because they are particulate systems by their very nature, administration of emulsions into the blood system must be viewed with care, requiring precautions and special requirements. Indeed, until the 1950s it was not realized that one essential requirement for injectable emulsions was that the droplet diameter must be below 1 pm in diameter. Otherwise there is always a finite risk of blocking the smaller blood vessels. 

Linoleic acid and alpha-linoleic acid are essential fatty acids that are provided in any long-term parenteral nutrition by administering fat emulsions at least twice a week. Fatty acid deficiency is a common complication of severe end-stage liver disease. The ability of short-term intravenous lipid supplementation to reverse fatty acid deficiencies has been studied in patients with chronic liver disease and low plasma concentrations of fatty acids (914). Shortterm supplementation failed to normalize triglycerides. 

Their use as an injectable warrants assurance of product sterility. Whereas the FDA-preferred heat-sterilization process is acceptable for total parenteral nutritional (TPN) emulsions, it could affect chemical as well as physical stability of emulsions containing therapeutic agents. Recently, data supporting the Liter sterilization of emulsions have been published. 

Table 1 Some commercial lipid emulsions for parenteral nutrition...

Typical solid lipids used are glycerides and/or fatty acids, and may constitute 30% of the formulation. These are from the same family of lipids found in parenteral nutrition emulsions, such as Intralipid, which have been successfully administered intravenously for several decades. Typical excipients are Dynasan 112, composed of short chain fatty acids, Compritol, lecithin, used as an emulsifier, and surfactants such as polysorbate 80, polaxamer 188, PVP, bile salts such as sodium glycocholate, and Span 85. Water can be replaced with oils or PEG 600 to yield dispersions which can be filled into soft gelatin capsules. 

Washington, C. The stability of intravenous fat emulsions 33. in total parenteral nutrition mixtures. Int. J. Pharm. 1990,... 

Two children developed neurological complications of fat emulsion therapy, including focal and generalized seizures, weakness, and altered mental status, before any systemic findings were in evidence (15). Biopsy and autopsy findings included cerebral endothehal and intravascular lipid deposition. These complications are potentially reversible with alteration of the parenteral nutrition content, highlighting the importance of their early recognition. 

Hematological abnormalities have been found to be associated with prolonged administration of intravenous fat emulsion in children on a program of long-term cyclic parenteral nutrition. Recurrent thrombocytopenia is common and platelet lifespan is reduced. In one study (80), thrombocytopenia occurred in 66% of patients, but most of these had taken drugs that might have interfered with platelet function. Hypercoagulability was not found in the majority of cases. 

It seems clear that platelet counts should be performed on a regular basis in patients receiving prolonged parenteral nutrition with fat emulsion (Intralipid). If a low platelet count develops, reduction or termination of administration is indicated (76). Clinical findings further point to hyperactivity of the macrophage in the reticuloendothelial system related to long-term treatment with Intralipid. 

In a prospective prevalence study of liver disease in 90 patients with permanent intestinal failure receiving parenteral nutrition hver biopsy was performed in 57 (95). Chronic cholestasis developed in 58 patients after a median of 6 (range 3-132) months, and 37 developed comphcated liver disease after a median of 17 (range 2-155) months. Chronic cholestasis was significantly associated with a risk of liver disease independent of parenteral nutrition, a bowel remnant shorter than 50 cm, and a lipid intake of 1 g/kg/day or more hver disease related to parenteral nutrition was significantly associated with chronic cholestasis and a parenteral hpid intake of 1 g/kg/day or more. The authors concluded that the prevalence of hver disease increased with the duration of parenteral nutrition and was one of the main causes of death in patients with permanent intestinal failure. Parenteral intake of long-chain hpid emulsion should be restricted to less than 1 g/kg/day. 

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