Lipid emulsion in parenteral nutrition

Koletzko B, Goulet O. Fish oil containing intravenous lipid emulsions in parenteral nutrition-associated cholestatic Uver disease. Curr Opin Clin Nutr Metab Care 2010 13(3) 321-6. 

Rollins MD, Scaife ER, Jackson WD, Meyers RL, Mulroy CW, Book LS. Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome. Nutr Clin Pract 2010 25(2) 199-204. 

M. Adolph, Lipid emulsions in parenteral nutrition. AnrLNji Metah.. 43,1-13 (1999). 

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. 

Driscoll DF, Adolph M, Bistrian BR. Lipid emulsions in parenteral nutrihon. In Rombeau JL, Rolandelli RH, eds. Qinical Nutrition Parenteral Nutrition, 3rd ed. Philadelphia, Satmders, 2001 35-59. 

In 10 children who were exclusively given a fish oil-based lipid emulsion during parenteral nutrition for a median duration of 14 weeks, the serum bilirubin fell in 8 there was also a 24% increase in high-density lipoprotein cholesterol and significant falls in serum low-density lipoprotein, very low-density lipoprotein, and total cholesterol, and triglyceride concentrations /35 7-... 

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]. 

The role of lipid emulsions in cholestasis associated with long-term parenteral nutrition has been investigated retrospectively in 10 children with a total of 23 episodes of cholestasis, associated with thrombocytopenia in 13 cases (104). Changes in lipid delivery, associated with increased daily amounts, preceded complications in more than half the cases, while temporary reduction in lipid administration led to normalization of bilirubin in 17 episodes. The authors concluded that lipid supply is one of the risk factors for cholestasis associated with parenteral nutrition. They recommended that when cholestasis occurs, lipid should be temporarily withdrawn, especially if there is associated thrombocytopenia. 

The United States Food and Drug Administration issued a safety alert in 1994 regarding the potentially life-threatening formation of precipitates in parenteral nutrition admixtures (148). They had received reports of two deaths and at least two cases of respiratory distress during intravenous infusion of a three-in-one parenteral nutrition mixture (amino acids, carbohydrates, lipids). The mixture contained 10% FreAmine III (amino acids -I- magnesium acetate -I- phosphoric acid -I- potassium chloride -I- sodium acetate -I- sodium chloride), dextrose, calcium gluconate, potassium phosphate, other minerals, and a lipid emulsion. The solution may have contained a precipitate of calcium phosphate. Autopsies revealed diffuse microvascular pulmonary emboli containing calcium phosphate. 

Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet JC, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. J Parenter Enteral Nutr 2000 24(6) 345-50. 

A fish oil-based intravenous lipid emulsion in the treatment of liver disease associated with parenteral nutrition has been compared with soybean oil in an open study in 42 infants with short bowel syndrome who developed cholestasis [35 ]. There were three deaths and one liver transplantation in those who received the fish oil, compared with 12 deaths and 6 transplants in those who received soybean oil The fish oil was not associated with hypertriglyceridemia, coagulopathy, or deficiency of essential fatty acids. 

G- Groiie. S. Jacobsen, and A. Wreilmd. Lipid emulsions and technique of peripheral administration in parenteral nutrition, pp. 335-362, in Ref. 42. 

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. 

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. 

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. 

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. 

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. 

Drugs with a high lipid content, when given concurrently with lipid-containing parenteral nutrition, can aggravate the problems of lipid overload (29). The anesthetic, propofol, which is used for continuous sedation in a dose of 1-3 mg/kg/hour (an equivalent of 300-500 ml of a 10% fat emulsion), may aggravate the symptoms and pathological effects of fat overload (29). 

A number of early case reports described warfarin resistance in patients taking enteral feeds that contained high levels of added vitamin Kx- These products were then reformulated to contain lower amounts of vitamin Kx, commonly now about 4 to 10 micrograms per 100 mL however, some cases of interactions have still been reported, and one study in children reported that those receiving enteral nutrition (mostly vitamin K enriched formula) required 2.4-fold higher maintenance warfarin doses. Lipid emulsions containing soya oil might contain sufBcient natural vitamin Kx to alter warfarin requirements. Parenteral multivitamin preparations may also contain vitamin Kx. 

Fat emulsions used for parenteral use containing soya oil may themselves contain sufficient vitamin Kj for daily needs. Parenteral multivitamin preparations may also contain important levels of vitamin Kj. It would be advisable to keep the vitamin Kj intake constant in any patient requiring long-term supplemental or total parenteral nutrition and warfarin. If the amount of lipid and/or multivitamins is altered, antieipate a... 

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