Insulin Instability in Parenteral Nutrition Admixtures.

BACKGROUND: Biosynthetic human recombinant short-acting insulin is added to parenteral nutrition (PN) admixtures to nourish glucose-intolerant patients. Insulin, however, is electrostatically attracted and inactivated by ethyl-vinyl-acetate (EVA) bags and filling system tubes. Our aim was to verify and quantify the presence of insulin in PN with and without intravenous lipid emulsion (ILE), just after addition (T0) until the infusion's end (T24). METHODS: Four undiluted samples of 12 different PN complete admixtures (6 with ILE and 6 without), each containing 250 g of glucose in a 2000 mL volume, were taken and analyzed at T0 and T24 by an automated electrochemiluminescence immunoassay after the addition of biosynthetic human recombinant short-acting insulin at increasing doses (from 6 to 72 IU/bag) by an automated compounding device. Assay sensitivity was set at 2 µIU/mL. Admixtures with and without ILE were compared in terms of insulin-detected amounts at T0 and T24. RESULTS: Regardless of the amount initially provided, insulin was missing in PN without ILE. In admixtures with ILE, the greater the insulin and ILE doses initially included, the higher the insulin availability at T0 and T24, both in absolute terms and as a percentage of the initial amount (from 3 to 81% at T0 and from 2.5 to 72.5% at T24). ILE may prevent insulin attraction to plastic surfaces. CONCLUSIONS: Insulin is recovered in the presence of ILE in PN even though considerable amounts are untraceable. This aspect needs verification. Until then, insulin should safely be injected in a different manner in uncontrolled situations.

Potential intake of vitamins "A" and "D" through branded intravenous lipid emulsions: Liquid Chromatography-Tandem Mass Spectrometry Analysis.

No data exist for vitamin A group and vitamin D2/D3 content in branded intravenous lipid emulsions (ILEs). Our goal is to evaluate and quantify their concentrations in different ILEs to assess whether they are clinically relevant. Analyses were carried out in triplicates on six ILEs: 1) 30% soybean oil-based, 2) 20% olive-soybean oil based, 3) 10 + 10% soybean - MCT coconut oil based, 4) 20% soybean-olive-MCT-fish oil based, 5) 20% soybean-MCT-fish oil based and 6) 10% pure fish oil based, respectively. Retinol group (vitamin A) and ergo-chole-calciferol (vitamin D2/D3) were analyzed and quantified by a quali-quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method after potassium hydroxide alkaline hydrolysis, hexane extraction, reverse phase-liquid chromatography and specific multiple-reaction-monitoring (MRM) detection. On average, measured retinol content was in the range of 200-1000 µg/L in ILEs (1,2, and 3), whereas it was higher (1000-2000 µg/L) in the ILEs containing fish-oil. Vitamin D content was in the range of 1-10 µg/L in the fish-oil based ILEs, but undetectable in those ILEs containing purely vegetable oils. This study shows that vitamin A and D contents are variably present in ILEs based on their different lipid sources. Both contents should be explicitly mentioned in the products.

Phytonadione Content in Branded Intravenous Fat Emulsions.

BACKGROUND: Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. MATERIALS AND METHODS: Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. RESULTS: Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity ( r = 0.99), and accuracy (coefficient of variation <5%). CONCLUSIONS: Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.

The spectrum of plant and animal sterols in different oil-derived intravenous emulsions.

Intravenous lipid constituents have different effects on various biological processes. Some of these effects are protective, while others are potentially adverse. Phytosterols, in particular, seem to be implicated with parenteral nutrition-associated cholestasis. The aim of this study is to determine the amount of plant and animal sterols present in lipid formulations derived from different oil sources. To this end, animal (cholesterol) and plant (beta-sitosterol, campesterol, and stigmasterol) sterols in seven different commercially available intravenous lipid emulsions (ILEs) were quantified by capillary gas chromatography after performing a lipid extraction procedure. The two major constituents of the lipid emulsions were cholesterol (range 14-57% of total lipids) and beta-sitosterol (range 24-55%), followed by campesterol (range 8-18%) and stigmasterol (range 5-16%). The fish oil-derived formulation was an exception, as it contained only cholesterol. The mean values of the different sterols were statistically different across ILEs (P = 0.0000). A large percentage of pairwise comparisons were also statistically significant (P = 0.000), most notably for cholesterol and stigmasterol (14 out of 21 for both), followed by campesterol (12 out 21) and beta-sitosterol (11 out 21). In conclusion, most ILEs combined significant amounts of phytosterols and cholesterol. However, their phytosterols:cholesterol ratios were reversed compared to the normal human diet.

Vitamin A and vitamin E isoforms stability and peroxidation potential of all-in-one admixtures for parenteral nutrition.

BACKGROUND: In all-in-one admixtures (AIOs), vitamins can be degraded and lipid can be peroxidized by light exposure, oxygen action, and multiple chemical interactions. AIM: We investigated the impact of three commercial lipid emulsions and two multivitamin preparations on vitamin A and vitamin E chemical stability and lipid peroxidation potential of AIOs. METHODS: A soybean oil (Soy), soybean/medium-chain triacylglycerol oil (MCT), and olive/soybean oil (Olive)-based emulsion (all 20%), and a lyophilized (Lyo) and emulsified (Emu) multivitamin compounds, were tested. Two AIOs for each lipid emulsion were prepared, the former with Lyo and the latter with Emu. The concentrations of retinol palmitate, alpha-gamma-delta-tocopherol, and malondialdehyde were analyzed in AIOs, immediately (T0) and 24 hours (T24) after compounding. RESULTS: Retinol palmitate, and alpha- and gamma-tocopherol were more stable in MCT-AIOs than in both Soy-AIOs and Olive-AIOs (p < 0.013; p < 0.001 respectively). Furthermore alpha-tocopherol was more stable in Lyo-AIOs than in Emu-AIOs (p < 0.004). Malondialdehyde (MDA) increased differently among the admixtures; however the concentrations were similar in all AIOs at T24. CONCLUSIONS: The differences in retinol palmitate stability were due both to lipid emulsions per se and to interaction between lipid emulsions and multivitamin preparations. The alpha-gamma-tocopherol stability depended on both lipid emulsions and multivitamin preparations. In tested AIOs there was a different degradation rate of fat-soluble vitamins to keep the same lipid peroxidation level, since MDA concentrations at T24 were similar among AIOs.

Peroxidation potential of lipid emulsions after compounding in all-in-one solutions.

OBJECTIVES: We investigated the peroxidation potential of fat emulsions in all-in-one solutions (AIOs). METHODS: Three 20% emulsions were compared: soybean oil (SO; 60% polyunsaturated fatty acids [PUFAs], alpha-tocopherol:PUFAs = 0.44), soybean plus medium-chain triacylglycerol (SO-MCT; 31% PUFAs, alpha-tocopherol:PUFAs = 0.35), and olive oil (OO; 21% PUFAs, alpha-tocopherol:PUFAs = 1.42). For each emulsion, six AIO solutions were prepared by adding 250 mL of emulsion to a lipid-free solution. Lipid peroxide (LPX) and malondialdehyde (MDA) concentrations were evaluated in fat emulsions, lipid-free solutions, and AIOs immediately (T0) and 24 h (T24) after lipid addition. Statistical analysis was done with analysis of variance. RESULTS: Fat emulsion LPX in SO-MCT was lower than that in SO (P = 0.015) and OO (P = 0.024); LPX in SO was greater than that in OO (P = 0.013); MDA in SO was greater than that in SO-MCT (P = 0.001) and OO (P = 0.013); and MDA in SO-MCT was greater than that in OO (P = 0.001). In comparison with MDA at AIO-T0, MDA at AIO-T24 increased in SO (P = 0.005) and SO-MCT (P < 0.001) and decreased in OO (P = 0.003); at AIO-T24, LPX was greater in SO, but not significantly. CONCLUSIONS: In AIO bags, LPX occurred within 24 h after the addition of the lipid emulsion and seemed to be directly related to the PUFA content and inversely related to the alpha-tocopherol:PUFA ratio of the emulsion.