Inflammatory processes involved in the alteration of liver function biomarkers in adult hospitalized patients treated with parenteral nutrition.

Introduction: Liver damage has been associated with the accumulation of phytosterols (PS) in patients treated with parenteral nutrition (PN). We aimed to study the association of inflammatory markers with liver function biomarker (LFB) alterations in patients treated with PN containing PS. Materials and methods: Prospective observational study. Simple linear and stepwise multiple linear regression tests and interactions were performed. Results: Nineteen patients were included. In the multivariable model, determinations based on LFBs as dependent and phytosterols (and their fractions) as independent variables showed an association between increases in gamma-glutamyltransferase (GGT) and lanosterol (p < 0.001), stigmasterol (p < 0.001), interleukin-10 (IL-10) × total phytosterols (Phyt) (p < 0.009), tumor necrosis factor-α (TNF-α) × Phyt (p < 0.002), IL-10 × sitosterol (p < 0.002), TNF-α × sitosterol (p < 0.001), IL-10 × campesterol (p < 0.033), IL-10 (p < 0.006 and p < 0.015), TNF-α (p < 0.048 and p < 0.027). Increases in alanine aminotransferase (ALT) were associated with Phyt (p < 0.006), lanosterol (p < 0.016), C-reactive protein (CRP) × campesterol (p < 0.001), interleukin-6 (IL-6) × stigmasterol (p < 0.030), CRP (p < 0.08), and IL-6 (p < 0.042). Alkaline phosphatase (AP) increases were associated with CRP (p < 0.002). Discussion: Inflammation in the presence of plasmatic PS seems to have a synergistic effect in impairing liver function, mainly altering GGT but also ALT.

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy.

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed.

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 ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-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 ω-3 fatty acids or a mixture of ω-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 ω-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 ω-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 ω-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. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

Phytosterolaemia 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 hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (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 soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 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.

Determinación de fitoesteroles en emulsiones lipídicas para nutrición parenteral / Phytosterol determination in lipid emulsions for parenteral nutrition

Objetivo: La presencia de fitoesteroles en emulsiones lipídicas de origen vegetal se ha relacionado con la aparición de alteraciones de los parámetros de la función hepática. El objetivo es determinar la presencia de fitoesteroles en las emulsiones registradas en el mercado farmacéutico. Método: Se analizaron tres-cuatro lotes no consecutivos de seis marcas distintas de emulsiones lipídicas (Clinoleic(R), Intralipid(R), Lipofundina(R), Lipoplus(R), Omegaven(R) y Smoflipid(R)) y las diferencias en contenido de fitoesteroles totales entre marcas y entre lotes se estudiaron estadísticamente (ANOVA de un factor, aproximación no paramétrica de Kruskal-Wallis y análisis post hoc Scheffé; p < 0,05). Resultados: Se encontró ausencia de fitoesteroles en el preparado Omegaven(R) con aceite de pescado. El contenido más alto de fitoesteroles (422,4 ± 130,5 µg/mL) coincidió con el porcentaje más alto de aceite de soja (Intralipid(R)). En el resto de las emulsiones se detectaron concentraciones de fitoesteroles entre 120 y 210 µg/mL, relacionadas con el contenido de aceite de soja. Se observaron diferencias estadísticamente significativas entre todas las marcas de emulsiones lipídicas (F = 42,97; p = 0,000) y entre lotes no consecutivos. Clinolenic(R) (F = 23,59; p = 0,000); Intralipid(R) (F = 978,25; p = 0,000); Lipofundina(R) TCL/TCM (F = 5,43; p = 0,045); Lipoplus(R) (F = 123,53; p = 0,000),; y Smoflipid(R) (16,78; p = 0,000). Excepto en el caso de la Lipofundina(R) TCL/TCM las diferencias entre lotes fueron marcadas. Conclusiones: Las emulsiones lipídicas registradas en el mercado farmacéutico español contienen cantidades variables de fitoesteroles en función de la marca comercial y el lote. La determinación del contenido de fitoesteroles, actualmente no declarados, permitiría desarrollar estrategias para prevenir o tratar la aparición de estas alteraciones

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 different providers (Clinoleic(TM), Intralipid(TM), Lipofundina(TM), Lipoplus(TM), Omegaven(TM) and Smoflipid(TM)) 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(TM), 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(TM) (F = 23.59; p = 0.000), Intralipid(TM) (F = 978.25; p = 0.000), Lipofundina(TM) TCL/TCM (F = 5.43; p = 0.045), Lipoplus(TM) (F = 123.53; p = 0.000) and Smoflipid(TM) (16.78; p = 0.000). Except for Lipofundina(TM) TCL/TCM, the differences between batches were marked. Conclusions: Lipid emulsions, registered on Spanish pharmaceutical market, contain variable quantities of phytosterols dependent on commercial brand and batch

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 different 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 commercial brand and  batch.

Objetivo: La presencia de fitoesteroles en emulsiones lipídicas de origen vegetal se ha relacionado con la aparición de alteraciones de los parámetros de la  función hepática. El objetivo es determinar la presencia de fitoesteroles en las  emulsiones registradas en el mercado farmacéutico.Método: Se analizaron tres-cuatro lotes no consecutivos de seis marcas  distintas de emulsiones lipídicas (Clinoleic®, Intralipid®, Lipofundina®,  Lipoplus®, Omegaven® y Smoflipid®) y las diferencias en contenido de  fitoesteroles totales entre marcas y entre lotes se estudiaron estadísticamente  (ANOVA de un factor, aproximación no paramétrica de Kruskal-Wallis y análisis  post hoc Scheffé; p < 0,05).Resultados: Se encontró ausencia de fitoesteroles en el preparado Omegaven® con aceite de pescado. El contenido más alto de fitoesteroles (422,4 ± 130,5  µg/mL) coincidió con el porcentaje más alto de aceite de soja (Intralipid®). En el resto de las emulsiones se detectaron concentraciones de fitoesteroles entre 120  y 210 µg/mL, relacionadas con el contenido de aceite de soja. Se  observaron diferencias estadísticamente significativas entre todas las marcas de  emulsiones lipídicas (F = 42,97; p = 0,000) y entre lotes no consecutivos.  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),; y Smoflipid® (16,78; p = 0,000). Excepto en el caso de la  Lipofundina® TCL/TCM las diferencias entre lotes fueron marcadas.Conclusiones: Las emulsiones lipídicas registradas en el mercado farmacéutico español contienen cantidades variables de fitoesteroles en función  e la marca comercial y el lote. La determinación del contenido de fitoesteroles, actualmente no declarados, permitiría desarrollar estrategias para prevenir o tratar la aparición de estas alteraciones.

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.