Enteral omega-3 fatty acid supplementation in adult patients with acute respiratory distress syndrome: a systematic review of randomized controlled trials with meta-analysis and trial sequential analysis

Controversy remains as to whether enteral supplementation of omega-3 fatty acids (FA) could improve outcomes in patients with acute respiratory distress syndrome (ARDS). Thus, we did a meta-analysis and aimed to investigate the benefit and harm of enteral omega-3 FA supplementation in adult patients with ARDS. Databases including PubMed, Embase, the Cochrane Register of Controlled Trials, and Google Scholar were searched to find relevant articles. Randomized controlled trials (RCTs) comparing enteral omega-3 FA supplementation with a control or placebo intervention in adult patients with ARDS were included. The primary outcome was all-cause 28-day mortality. We used the Cochrane Collaboration methodology. Seven RCTs with 955 adult patients qualified for inclusion, and all the selected trials were considered as at high risk of bias. The use of enteral omega-3 FA did not significantly reduce all-cause 28-day mortality [relative risk (RR), 0.90; 95 % confidence intervals (CI), 0.68-1.18; p = 0.44; I (2) = 31 %; random effects]. Trial sequential analysis indicated lack of firm evidence for a 20 % RR reduction in all-cause 28-day mortality. PaO2/FiO(2) ratio was significantly increased in the omega-3 FA group on day 4 [weighted mean difference (WMD), 45.14; 95 % CI, 16.77-73.51; p = 0.002; I (2) = 86 %; random effects] and day 7 (WMD, 33.10; 95 % CI, 1.67-64.52; p = 0.04; I (2) = 88 %; random effects). Meta-analysis using a random effects model showed no significant differences in ventilator-free days (VFD) (WMD, 2.47 days; 95 % CI, -2.85 to 7.79; p = 0.36; I (2) = 91 %) or intensive care unit-free days (ICU) (WMD, 2.31 days; 95 % CI, -2.34 to 6.97; p = 0.33; I (2) = 89 %) between the two groups. Among patients with ARDS, enteral supplementation of omega-3 FA seemed ineffective regarding all-cause 28-day mortality, VFD, and ICU-free days. Routine use of enteral omega-3 FA cannot be recommended based on the available evidence.