Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients

Background: Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. Methods: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. Results: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p= 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p= 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD -3.53; 95% CI - 6.16, - 0.90; p= 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p= 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. Conclusion: Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact.