Intravenous n-3 fatty acids in the critically ill.

PURPOSE OF REVIEW: Lipid emulsions are an integral part of parenteral nutrition. Enteral nutrition is the preferred route to feed critically ill patients and parenteral nutrition is used in case of contraindications or when enteral nutrition does not reach the nutritional goals. n-3 Lipids are included into some newer lipid emulsions including fish oil or may be added by a fish oil-based lipid emulsion to lipid emulsion without fish oil. This review focuses on recent clinical trials, metaanalyses, and guidelines of parenteral nutrition with n-3 lipids in critically ill patients. RECENT FINDINGS: Two single-center studies report a mortality benefit of adding fish oil-based lipid emulsions to the parenteral nutrition. Metaanalyses performed without these two studies had demonstrated beneficial effects of n-3 lipids regarding infections, length of stay, and time of mechanical ventilation but not on mortality. However, all metaanalyses judged the database derived from the underlying studies as not sufficient for a firm recommendation. Consecutively, guidelines and expert groups issue very cautious recommendations for the use of n-3 lipids in parenteral nutrition. SUMMARY: Beneficial effects of n-3 lipids in trials and metaanalyses became available; however, high-quality multicenter randomized controlled trials are needed before more endorsing recommendation will be available.

Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS. METHODS: Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis. RESULTS: Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. CONCLUSION: SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition.

Fatty acids differentially influence phosphatidylinositol 3-kinase signal transduction in endothelial cells: impact on adhesion and apoptosis.

In contrast to n-6 fatty acids like arachidonic acid (AA), the anti-inflammatory potential of n-3 fatty acids such as docosahexaenoic acid (DHA) has been demonstrated. We examined the phosphatidylinositol (PI)3-kinase dependent effects of AA versus DHA on monocyte rolling, adhesion and transmigration through inflammatory activated human umbilical venous endothelial cells (HUVEC) as well as on apoptosis, to investigate the impact on vascular inflammation. HUVEC were pre-incubated with AA, DHA or sham, and stimulated with VEGF, TNF-alpha or staurosporine. Rolling and adhesion were investigated by means of a parallel flow chamber; transmigration was performed in a static assay. Activation of PI3-kinase was measured as phosphorylation of protein kinase B (Akt). Apoptosis was determined by caspase-3 activity and annexin-V analysis. Pre-incubation of HUVEC with DHA markedly decreased TNF-alpha-induced monocyte rolling, adhesion, and transmigration, although expression of endothelial adhesion molecules was unchanged. In contrast, AA increased TNF-alpha-induced rolling. Both fatty acids did not alter TNF-alpha-mediated upregulation of the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The divergent effects of AA and DHA were abrogated with PI3-kinase inhibitors. After pre-incubation with DHA, VEGF-, TNF-alpha- and staurosporine-induced phosphorylation of Akt was decreased when compared to AA. DHA pre-incubation significantly increased staurosporine-induced apoptosis. In addition, DHA in comparison to AA augmented staurosporine-mediated increase in caspase-3 activity. In conclusion, DHA-induced a reduction in rolling, adhesion and transmigration of monocytes through inflammatory activated HUVEC that is in part PI3-kinase dependent. PI3-kinase driven phosphorylation of Akt and apoptosis of HUVEC as contribution to the resolution of inflammation is differentially modulated by DHA versus AA.

Fish oil in the critically ill: from experimental to clinical data.

PURPOSE OF REVIEW: The aim of this paper is to describe recent relevant literature concerning the role of n-3 lipids derived from fish oil in clinical nutrition in an intensive care setting. RECENT FINDINGS: N-3 fatty acids compete with arachidonic acid for metabolism to lipid mediators and exert profound effects on second mediator generation and dependent cellular functions. In experimental models, dietary and parenteral use of fish oil was shown to protect the gut by increasing its perfusion. In contrast, use of immunonutrition including fish oil in critical ill patients or patients with severe sepsis may exert an excess mortality. Using parenteral fish oil in surgical patients promising data became available. In septic patients, immunologic effects of fish oil-based lipid emulsions have been found and intravenous supplementation with fish oil may have a beneficial impact on mortality and length of stay. For both patient groups, however, prospective data from randomized trials are lacking. SUMMARY: N-3 lipids exhibit strong immunologic properties. They offer the possibility to counterbalance the negative effects of conventional n-6 fatty acids. Recent studies exhibit positive effects of intravenous use of fish oil on immunologic functions and clinical parameters in surgical and septic patients.