The relationship between the parenteral dose of fish oil supplementation and the variation of liver function tests in hospitalized adult patients

Background Hepatic dysfunction is a complication associated with parenteral nutrition (PN). Our primary objective was to study the relationship between doses of intravenous fish oil (FO) emulsion in PN and the variation in the main liver function tests (LFTs) in hospitalized PN-treated adults. As a secondary objective, we studied the safety of FO administration. Methods We conducted a retrospective study in adult patients receiving FO supplementation in PN. Demographic, nutritional and safety variables were collected. Variation of LFTs was defined as the difference between values just before the first administration of FO and values at the end of PN. A multiple linear regression was performed to study the association between PN-lipids (FO or vegetable) and the variation of each LFT; the following variables were used to adjust the effect of lipids: sepsis, length of stay in the intensive care unit and lipids dose. Student t-test was used to study safety variables. Data were analyzed using SPSS 19.0. Results Patients (53, median age 68 years (24-90); 62 % men) with the principal diagnosis of digestive neoplasm (42 %) received PN for a median of 19 (7-75) days. In the multivariate analysis, the amount of FO was related to a decrease in gamma-glutamyl transferase (GGT) (B = −2.23;CI95 % = −4.41/-0.05), a decrease in alkaline phosphatase (AP) (B = −1.23;CI95 % = −2.07/-0.37), and a decrease in alanine aminotransferase (ALT) (B = −0.82; CI95 % = −1.19/-0.44). No differences were found in safety variables. Conclusions GGT, AP and ALT improved with FO PN-supplementation. Moreover, the improvement was greater when the doses of FO were higher. FO administration in PN is safe

Phytosterol determination in lipid emulsions for parenteral nutrition

Objective: The presence of phytosterols in vegetal lipid emulsions has been associated with alterations of liver function tests. Determination of phytosterols content, currently undeclared, would allow the development of strategies to prevent or treat these alterations. Method: 3-4 non-consecutive batches of 6 lipid emulsions from diffe rent providers (Clinoleic , Intralipid , Lipofundina , Lipoplus , Omegaven and Smoflipid ) were analyzed. Differences in total phytosterol assay between providers and batches were statistically studied by a one way ANOVA and Kruskal-Wallis non-parametric approximation and post hoc Scheffé test (p<0.05) Results: The absence of phytosterols was confirmed in Omegaven , emulsion based on fish oil. The highest assay of phytosterols (422.4±130.5 µg/mL) has been related with the highest percentage of soya bean oil in Intralipid. In the remaining emulsions, concentrations were from 120 to 210 µg/mL related to the percentage of soya bean oil. Statistically significant differences of phytosterol content in lipid emulsions were observed among different providers (F=23.59; p=0.000) as well as among non-consecutive batches. Clinolenic (F=23.59; p=0.000), Intralipid (F=978.25; p=0.000), Lipofundina TCL/TCM (F=5.43; p=0.045), Lipoplus (F=123.53; p=0.000) and Smoflipid (16.78; p=0.000). Except for Lipofundina TCL/TCM, the differences between batches were marked. Conclusions: Lipid emulsions, registered on Spanish pharmaceutical market, contain variable quantities of phytosterols dependent on commer cial brand and batch

Risk factors of hepatic function alterations in hospitalized adult patients treated with short-term parenteral nutrition receiving the same lipid composition at the same dose

Background: High doses and vegetable origin of lipid emulsions (LE) are prominent factors for liver test (LT) alterations in patients treated with parenteral nutrition (PN). This study aims to determine incidence of LT alterations, and risk factors related to these alterations in patients with short term PN with homogenous LE. Methods: Adult non-critically ill hospitalized patients, with normal LTs at the beginning of PN, receiving 0.8 g/kg/day of an olive/soybean LE were included. A paired Student t-test was applied to compare final with initial LT values. LT variation (end vs start of PN) according to type of surgery and infection was studied by means of an analysis of the variance. Univariate and multivariate analyses were constructed to relate the variations of each of the 4 LTs with the adjustment variables. Results: One hundred eighty one patients (66.57 ± 12.89 years; 72.4% men), 66.8% suffered from cancer. Final LT values increased from initial values for gamma-glutamyltransferase (GGT) 2.69 ± 2.49 μkat/L vs 0.55 ± 0.36 μkat/L, alkaline phosphatase (AP) 1.97 ± 1.49 μkat/L vs 1.04 ± 0.33 μkat/L, and alanine aminotransferase (ALT) 0.57 ± 0. 92 μkat/L vs 0.32 ± 0.26 μkat/L. GGT and AP variations were associated with days of PN; GGT, AP and total bilirubin with surgical patients, AP variations with infection, and GGT with cancer. Multivariate analysis: elevation of GGT, AP and ALT was related to infection, days of PN and surgery. Conclusions: Factors that increased the risk of LTs elevation during short term PN treatment were duration of PN, surgery, cancer, and infection associated with oxidative stress

A randomised study on the clinical progress of high-risk elective major gastrointestinal surgery patients treated with olive oil-based parenteral nutrition with or without a fish oil supplement

n-3 Fatty acids have clinical benefits. The primary aim of the present study was the assessment of infection in patients who underwent major high-risk elective gastrointestinal surgery receiving postoperatively fish oil (FO)-supplemented parenteral nutrition (PN), compared with those receiving a standard olive oil (OO) emulsion. The secondary aims were the assessment of anti-inflammatory response and evaluation of tolerance and safety of these emulsions. A prospective, randomised, double-blind study was performed in patients requiring at least 5 d of PN. An isoenergetic and isoproteic formula was administered: group A received OO alone, while group B received OO that was partially replaced with FO (16.6 %, w/w). End points were outcome measures (mortality, sepsis, infection, hospitalisation days and PN duration), inflammatory response (C-reactive protein (CRP), prealbumin and leucocytes) and safety (TAG and glucose metabolism, and liver and kidney function). Statistical analysis was done using Student's t test and Fisher's exact test (P < 0.05). Twenty-seven patients were evaluated, with thirteen patients receiving FO. In this group, a significantly lower incidence of infections was found (23.1 v. 78.6 %, P = 0.007). CRP, prealbumin and leucocytes were not significantly different between the groups. There were no differences in safety parameters. We conclude that high-risk surgical patients receiving FO-supplemented PN for 5 d present a lower incidence of infection. Emulsions were safe and well tolerated

Development and validation of a simple high-performance liquid chromatography analytical method for simultaneous determination of phytosterols, cholesterol, and squalene in parenteral lipid emulsions.

A simple analytical method for simultaneous determination of phytosterols, cholesterol and squalene in lipid emulsions was developed owing to increased interest in their clinical effects. Method development was based on commonly used stationary (C18 , C8 and phenyl) and mobile phases (mixtures of acetonitrile, methanol and water) under isocratic conditions. Differences in stationary phases resulted in peak overlapping or coelution of different peaks. The best separation of all analyzed compounds was achieved on Zorbax Eclipse XDB C8 (150 × 4.6 mm, 5 μm; Agilent) and ACN-H2 O-MeOH, 80:19.5:0.5 (v/v/v). In order to achieve a shorter time of analysis, the method was further optimized and gradient separation was established. The optimized analytical method was validated and tested for routine use in lipid emulsion analyses

Phytosterolemia associated with parenteral nutrition administration in adult patients

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch; and in adult hospitalized patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. I. LE study: Totals and fractions of PS in 3-4 non-consecutive batches from 6 LE were analysed. II. Patient study: randomized, double-blind study of patients with at least 7 previous days of PN with 0.8 g/kg/day of an olive/soybean LE, were randomized (Day 0) 1:1 to olive/soybean (O/S) or 100% fish oil (FO) at a dose of 0.4 g/kg/day for 7 days (Day 7). Plasma PS, its fractions, total cholesterol on Days 0 and 7, their clearance, and their association with PS administered by LE were studied. In part I. LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soybean LE had the highest content of PS (422.36 ± 130.46 μg/mL). II. Patient study: 19 patients were included. In the O/S group, PS levels were maintained (1.11±6.98 μg/mL) from Day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6.21±4.73 μg/mL) and their fractions, except for campesterol and stigmasterol. Plasma PS on Day 7 were significantly associated with PS administered (R2=0.443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE

Selección de emulsiones lipídicas en nutrición parenteral: parámetros bioquímicos y hematológicos

Introducción: el patrón de ácidos grasos (AG) de las emulsiones lipídicas (EL) utilizadas en nutrición parenteral (NP) condiciona diferentes respuestas fisiológicas. Objetivos: estudiar si los criterios clínicos de prescripción de EL en NP establecidos en nuestro protocolo abierto y basados en recomendaciones se correlacionan con marcadores bioquímicos y hematológicos iniciales. Métodos: estudio observacional retrospectivo de cuatro años. Se recogieron variables demográficas, clínicas, nutricionales y analíticas al inicio de la NP. Se realizó un análisis uni y multivariante para estudiar la asociación entre los valores iniciales de los parámetros bioquímicos y hematológicos (PBHE) y el tipo de emulsión lipídica empleada. Resultados: de los 1.558 pacientes, 460 pacientes (29,5%) tenían PBHE al inicio de la NP y utilizaron mayoritariamente las combinaciones soja (AS) + triglicéridos de cadena media (MCT) + oliva (AO) + pescado (AP) (37,4%) y AS+MCT+AO (35,6%). Se encontraron diferencias estadísticamente signifiativas en el patrón EL utilizado entre los pacientes con y sin PBHE: patrón de AG con AP 44,8% vs.39,5%, respectivamente. Las situaciones clínicas con proteína C-reactiva (PCR) elevada se asociaron con mayor uso de EL con AP: AS+AO+AP (OR: 4,52 [IC 95%: 1,43-13,91] y AS+MCT+AO+AP (OR: 3,34 [IC 95%: 2,10-5,33]). En situaciones clínicas complejas asociadas con paciente crítico se utilizó EL con MCT: afectación hepática (AS+MCT OR: 2,42 [IC 95%: 1,03-5,68]) y afectación renal (AS+MCT+AP OR: 3,34 [IC 95%: 1,12-9,99]). Conclusiones: la inclusión protocolizada de PBHE al inicio de la NP permite complementar criterios clínicos y metabólicos en la elección de la EL

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients

Introduction: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of omega-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral omega-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. Materials and methods: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of omega-3 fatty acids or a mixture of omega-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of omega-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion. The main objective is to determine whether 5 days administration of intravenous omega-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality. Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. Discussion: Studies of omega-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient