Physicochemical stability of two types of intravenous lipid emulsion as total nutrient admixtures

Background: Recent data have demonstrated that total nutrient admixtures (T NAs) are unstable when the percentage of fat (PFAT) globules >5 mu m in dia meter constitute >0.4% of the total fat present and therefore can be consid ered pharmaceutically unfit for human administration. Methods: We studied f ive nutritionally balanced TNAs using two different products of different o il composition designed to feed adult patients weighing 40 to 80 kg in 10 k g increments, which were given in final volumes equal to 25 mL/kg. Final co ncentrations of amino acids, dextrose, and lipids were held constant for ea ch weight level. To provide cationic stress within clinical limits, calcium and magnesium were given in amounts equal to three times the usual daily d ose, at 15 mmol each. Five TNAs were made in duplicate and for each product (n = 20) and studied over 5 days. Lipid droplet counts were determined by laser light extinction and conducted at five intervals; immediately after p reparation at time 1 (T1), after 4 days at 4 degrees C +/- 2 degrees C (T2) , and then at 6 (T3), 24 (T4), and 30 (T5) hours during storage at 25 degre es C +/- 1 degrees C. At T3, a simulated patient infusion, set at a rate to deliver the entire volume over the next 24 hours, was begun. Samples taken at T3, T4, and T5, equal to 0, 18, and 24 hours, respectively, of the simu lated patient infusion, were collected from the terminal infusion port of t he TV administration set. Mean particle size (MPS) was determined by dynami c light scatter at T1, T3, and T5. Dependent variable analyses included the PFAT globules > 1.75 and 5 mu m and MPS. A repeated-measure two-way ANOVA assessing treatment and time was performed. Results: The MCT/LCT-based TNAs had significantly fewer enlarged fat globules >1.75 mu m (P < .0001) and > 5 mu m (p = .046), and smaller MPS (p < .0001) than TNAs made with the pure LCT emulsion. Of the 20 TNAs studied, 4 demonstrated visible evidence of i nstability (ie, heavy creaming or free oil), each occurring on day 5 only w ith the 70- and 80-kg LCT-based TNAs, and no evidence of instability with a dmixtures prepared from MCT/LCT Lipid emulsions (chi(2) analysis: p < .05). Conclusions: Because the final macronutrient concentrations were held cons tant, the instability seen with the LCT-based TNAs of higher volumes may re sult from dilution of the electrolyte concentrations that unfavorably alter s the electrical double layer and irreversibly commits the emulsion to an u nstable state. The greater physicochemical stability achieved with the MCT/ LCT-based TNAs, in turn, likely results from the smaller lipid droplet size s, which may be an inherent property of MCTs.