Lipid emulsion administration

The essential fatty acids in humans are linoleic acid (C-18 2 N-6) and a-linolenic acid (C18 3 N-3). Arachidonic acid (C20 4 N-6) is also essential but can be synthesized from linoleic acid. Administration of 2% to 4% of total daily calories as linoleic acid should be adequate to prevent essential fatty acid deficiency in adults (e.g., infusion of 500 mL of 20% intravenous lipid emulsion once weekly).7 Biochemical evidence of essential fatty acid deficiency can develop in about 2 to 4 weeks in adult patients receiving lipid-free PN, and clinical manifestations generally appear after an additional... 

PPN admixtures should be coinfused with intravenous lipid emulsion when using the 2-and-l PN because this may decrease the risk of phlebitis. Infectious and mechanical complications may be lower with PPN compared with central venous PN administration. However, because of the risk of phlebitis and osmolarity limit, PPN admixtures have low macronutrient concentrations and therefore require large fluid volumes to meet a patient s nutritional requirements. Given these limitations, every effort should be made to obtain central venous... 

Commonly administered LVPs include such products as Lactated Ringers Injection USP, Sodium Chloride Injection USP (0.9%), which replenish fluids and electrolytes, and Dextrose Injection USP (5%), which provides fluid plus nutrition (calories), or various combinations of dextrose and saline. In addition, numerous other nutrient and ionic solutions are available for clinical use, the most popular of which are solutions of essential amino acids or lipid emulsions. These solutions are modified to be hypertonic, isotonic, or hypotonic to aid in maintaining both fluid, nutritional, and electrolyte balance in a particular patient according to need. Indwelling needles or catheters are required in LVP administration. Care must be taken to avoid local or systemic infections or thrombophlebitis owing to faulty injection or administration technique. 

Lundberg BB, et al. A lipophilic paclitaxel derivative incorporated in a lipid emulsion for parenteral administration. J Control Release 2003 86 93. 

Mozzi G Benelli P, Bruzzese T, Gahnozzi MR, Bonabello A. (2002) The use of lipid emulsions for the iv administration of a new water soluble polyene antibiotic, SPK-843. J Antimicrob Chemother 49 321-325. 

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. 

Lundberg, B. B. (1997), A submicron lipid emulsion coated with amphiphathic polyethylene glycol for parenteral administration of paclitaxel (taxol),/. Pharm. Pharmacol., 49,16-21. 

A relative wealth of information relating to the application of zeta potential to injectable emulsions has been documented with respect to the use of total nutrient admixtures (TNA). Total nutrient admixtures are prepared by mixing the lipid emulsion with other components (i.e., dextrose, amino acids, and electrolytes) in a single container prior to administration. Depending on composition, the mixtures vary widely in their stability and may show clinically unacceptable coalescence after different periods of storage time. 

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. 

There is evidence that lipid emulsion, which is cleared by the Kupffer cells of the reticuloendothelial system, can adversely affect reticuloendothelial function by reducing its ability to remove blood-borne bacteria. In a study of the blood clearance and organ localization of viable S-radiolabelled Escherichia coli after slow intraperito-neal and more rapid intravenous administration of 20% fat emulsion in Sprague-Dawley rats, although there was... 

The developmental toxicity of a 20% lipid emulsion containing a 3 1 ratio of medium-chain to long-chain triglycerides has been examined in animals. Administration was once-daily intravenously to rats and rabbits during organogenesis. Maternal and embryo/fetal toxicity were also assessed. There were no adverse effects on fetal parameters for rats even in the presence of maternal toxicity. However, embryo and fetal toxicity (resorptions) and skeletal abnormahties were noted in rabbits (135). The adverse fetal effects were probably the result of dietary deprivation, maternal toxicity, or both rather than representing a direct teratogenic effect. 

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. 

Fig. (20a). Effects of resveratrol and piceid isolated from P. cuspidatum roots on serum LDL-ch and TG in rats fed com oil-10% cholesterol-1% cholic acid mixture for 1 week. Rats were orally administered with lipid emulsion (10 ml/kg body weight) for 1 week. Blood was taken by venous puncture 4 h after administration of the lipid emulsioiL Results are expressed as mean S.E. of 6-7 rats.

Pascual B, Ayestaran A, Montoro JB, et al. Administration of lipid-emulsion versus conventional amphotericin B in patients with neutropenia. Ann Pharmacother 1995 29 1197—1201. 

Greene HL, Philips BL, Franck L, et al. Persistently low blood retinol levels during and after enteral feeding of very low birth weight infants. Examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. Pediatrics 1987 79 892-200. 

There are conflicting data on the safety of administration of lipid emulsions to patients with ARDS. Discrepancies in trial data may be due to the use of differing lipid infusion rates and duration, as well as pre-existing lung status. 

Fig. (5) Effects of tea saponin on rat plasma triacylglycerol levels after oral administration of a lipid emulsion. Each point represents the mean s.e.m. of four rats. p<0.05, significantly different from lipid emulsion only-...

W emulsion (42.44). Von Dardel ei al. found that by administration of diazepam in an emulsion formulation, a highly significant reduction in the incidence of local vascular side effects can be achieved with no alteration in the therapeutic effect in comparison with the conventional preparative form (93). Ljungberg and Jeppsson (4) have shown in pharmacological studies that the LD i of diazepam is three times larger in the emulsion form than in the aqueous form, but there is no difference in the therapeutic effect. This caused a threefold increase in the therapeutic index in the case of the new lipid emulsion form. 

T. Morita, Y. Ishizuka. T. Arioka. Y. Mito, H. Yaginuma, and Y. Nozawa. Anti-candidal activity of GBR 14296, a new imidazole derivative intravenous administration in lipid emulsion form. Jpn. J. Med. Mycol,. 30 143-148, 1989. 

Although adrenaline is a first-line drug for pediatric advanced life support, there are emerging concerns that it impairs resuscitation with intravenous lipid emulsion in rats above a dose threshold of lOmicro-grams/kg [66 ]. In bupivacaine-induced cardiac arrest in rabbits adrenaline seemed to be necessary for return of spontaneous circulation, but was also associated with declining hemodynamic variables when the animals were resuscitated with intravenous lipid emulsion [67 ]. Some benefit to cardiac conduction may be achieved by hjqjer-tonic saline co-administration with lipid emulsion, as shown in rabbits [68 ]. 

Standard AIO admixtures are used in most adults patients. However, the patients requirements regarding calories and electrolytes may vary. Dialysis patients require restricted administration of electrolytes, however patients with severe diarrhoea need a higher amount of electrolytes. Standard parenteral nutrition admixtures cannot be used in severely ill paediatric patients, neonates and premature newborns. These patients need individualised admixtures. In premature infants and newborns the all-in-two system is preferred [53]. The lipid emulsion is mixed with the vitamin combination in a separate container and either administered with the amino acid/glucose/electrolyte admixture in parallel (Y-site) or via a separate venous access. 

The industrially manufactured two and three chambers are mixed just prior to infusion, by breaking the separation seals between the bag chambers. The content is mixed in the closed system and vitamins and trace elements can be added via an injection port prior to administration or administered as separate infusion solutions. Nutrition admixtures (all-in-one, all-in-two system) for the specific need of patients are prepared using industrially manufactured lipid emulsions and aqueous solutions containing amino acids, carbohydrates, electrolytes, vitamins and eventually trace elements. AU components are admixed in sterile empty infusion bags under conditions of aseptic handling (see Sect. 31.3). 

With the development of stable, energy dense, isotonic lipid emulsions for intravenous use (Table IV), the use of concentrated glucose solutions which have to be infused through large calibre central veins has decreased. Administration of nutrients by peripheral vein eliminates the complications associated with central catheter placement and use (Jako-bowski et al., 1979). Intravenous fat emulsions are manufactured from either soyabean or safflower oil, stabilized with 1.2% egg phospholipid, and made isotonic with 2.5% glycerol. Formulations are rich in essential fatty acids, yield 1.1 kcal/ml, and have a metabolic fate which is similar to that of naturally occurring chylomicrons. Liposyn, however, has only trace amounts of linolenic acid compared to the two other emulsions. In addition, carnitine is absent from all of the lipid emulsions. 

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