No abstract

IntroductionPrevious studies and a meta-analysis in surgical patients indicate that supplementing parenteral nutrition regimens with n-3 polyunsaturated fatty acids (PUFAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with improved laboratory and clinical outcomes in the setting of hyper-inflammatory conditions. Refined or synthetic fish oils are commonly used as a source of EPA and DHA. The objective of the present meta-analysis was to evaluate n-3 PUFA-enriched parenteral nutrition regimens in elective surgical and intensive care unit (ICU) patients.MethodsMedline was searched for randomized controlled trials comparing n-3 PUFA-enriched lipid emulsions with standard non-enriched lipid emulsions (i.e. soybean oil, MCT/LCT or olive/soybean oil emulsions) in surgical and ICU patients receiving parenteral nutrition. Extracted data were pooled by means of both random and fixed effects models, and subgroup analyses were carried forward to compare findings in ICU versus non-ICU patients.ResultsA total of 23 studies (n = 1502 patients: n = 762 admitted to the ICU) were included. No statistically significant difference in mortality rate was found between patients receiving n-3 PUFA-enriched lipid emulsions and those receiving standard lipid emulsions (RR= 0.89; 0.59, 1.33), possibly reflecting a relatively low underlying mortality risk. However, n-3 PUFA-enriched emulsions are associated with a statistically and clinically significant reduction in the infection rate (RR =0.61; 0.45, 0.84) and the lengths of stay, both in the ICU (-1.92; -3.27, -0.58) and in hospital overall (-3.29; -5.13, -1.45). Other beneficial effects included reduced markers of inflammation, improved lung gas exchange, liver function, antioxidant status and fatty acid composition of plasma phospholipids, and a trend towards less impairment of kidney function.ConclusionsThese results confirm and extend previous findings, indicating that n-3 PUFAs-enriched parenteral nutrition regimens are safe and effective in reducing the infection rate and hospital/ICU stay in surgical and ICU patients.

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

This systematic review and meta-analysis investigated ω-3 fatty-acid enriched parenteral nutrition (PN) vs standard (non-ω-3 fattyacid enriched) PN in adult hospitalized patients (PROSPERO 2018 CRD42018110179). We included 49 randomized controlled trials (RCTs) with intervention and control groups given ω-3 fatty acids and standard lipid emulsions, respectively, as part of PN covering ࣙ70% energy provision. The relative risk (RR) of infection (primary outcome; 24 RCTs) was 40% lower with ω-3 fattyacid enriched PN than standard PN (RR 0.60, 95% confidence interval [CI] 0.49-0.72; P < 0.00001). Patients given ω-3 fatty-acid enriched PN had reduced mean length of intensive care unit (ICU) stay (10 RCTs; 1.95 days, 95% CI 0.42-3.49; P = 0.01) and reduced length of hospital stay (26 RCTs; 2.14 days, 95% CI 1.36-2.93; P < 0.00001). Risk of sepsis (9 RCTs) was reduced by 56% in those given ω-3 fatty-acid enriched PN (RR 0.44, 95% CI 0.28-0.70; P = 0.0004). Mortality rate (co-primary outcome; 20 RCTs) showed a nonsignificant 16% reduction (RR 0.84, 95% CI 0.65-1.07; P = 0.15) for the ω-3 fatty-acid enriched group. In summary, ω-3 fatty-acid enriched PN is beneficial, reducing risk of infection and sepsis by 40% and 56%, respectively, and length of both ICU and hospital stay by about 2 days. Provision of ω-3-enriched lipid emulsions should be preferred over standard lipid emulsions in patients with an indication for PN. (JPEN J Parenter Enteral Nutr. 2020;44:44-57)

Nutritional lipids supplied during critical illness have been shown to modulate the host response to inflammation. In particular, inclusion of omega-3 fatty acids seems to have beneficial effects on cellular immunity and helps to maintain the balance between pro- and anti-inflammatory cytokines thereby preventing hyperinflammatory complications. In addition to improvements in the profile of lipid mediators generated, omega-3 fatty acids act as activating ligands of peroxisome proliferator-activated receptors and directly inhibit nuclear factor kappaB mediated proinflammatory signaling. We present an overview on the alterations in the metabolism of serum lipoproteins during sepsis and present data from clinical studies and discuss the significance of nutritional lipids and their role in immunomodulation with special emphasis on omega-3 fatty acids.