Omega-3 polyunsaturated fatty acids in critically ill patients with acute respiratory distress syndrome: A systematic review and meta-analysis

Abstract

Objective: Acute respiratory distress syndrome (ARDS) is characterized by an acute inflammatory response in the lung parenchyma leading to severe hypoxemia. Because of its anti-inflammatory and immunomodulatory properties, omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been administered to ARDS patients, mostly by the enteral route, as immune-enhancing diets with eicosapentaenoic acid, γ-linolenic acid, and antioxidants. However, clinical benefits of ω-3 PUFAs in ARDS patients remain unclear because clinical trials have found conflicting results. Considering the most recent randomized controlled trials (RCTs) and recent change in administration strategies, the aim of this updated systematic review and meta-analysis was to evaluate clinical benefits of ω-3 PUFA administration on gas exchange and clinical outcomes in ARDS patients.

Methods: We searched for RCTs conducted in intensive care unit (ICU) patients with ARDS comparing the administration of ω-3 PUFAs to placebo. The outcomes assessed were PaO₂-to-FiO₂ ratio evaluated early (3-4 d) and later (7-8 d), mortality, ICU and hospital length of stay (LOS), length of mechanical ventilation (MV), and infectious complications. Two independent reviewers assessed eligibility, risk of bias, and abstracted data. Data were pooled using a random effect model to estimate the relative risk or weighted mean difference (WMD).

Results: Twelve RCTs (n = 1280 patients) met our inclusion criteria. Omega-3 PUFAs administration was associated with a significant improvement in early PaO₂-to-FiO₂ ratio (WMD = 49.33; 95% confidence interval [CI] 20.88-77.78; P = 0.0007; I² = 69%), which persisted at days 7 to 8 (WMD = 27.87; 95% CI 0.75-54.99; P = 0.04; I² = 57%). There was a trend in those receiving ω-3 PUFA toward reduced ICU LOS (P = 0.08) and duration of MV (P = 0.06), whereas mortality, hospital LOS, and infectious complications remained unchanged. Continuous enteral infusion was associated with reduced mortality (P = 0.02), whereas analysis restricted to enteral administration either with or without bolus found improved early PaO₂ and FiO₂ (P = 0.001) and MV duration (P = 0.03). Trials at higher risk of bias had a significant reduction in mortality (P = 0.04), and improvement in late PaO₂-to-FiO₂ ratio (P = 0.003).

Conclusions: In critically ill patients with ARDS, ω-3 PUFAs in enteral immunomodulatory diets may be associated with an improvement in early and late PaO₂-to-FiO₂ ratio, and statistical trends exist for an improved ICU LOS and MV duration. Considering these results, administering ω-3 PUFAs appears a reasonable strategy in ARDS.

Keywords: Acute respiratory distress syndrome; Fish oil; Gas exchange; Omega-3.

Fig. 1

PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-analysis) flow diagram.

Fig. 2

Effects of fish oil on early PaO₂/FiO₂ in acute respiratory distress syndrome. CI, confidence interval; df, degrees of freedom; IV, instrumental variables; PUFA, polyunsaturated fatty acids; SD, standard deviation.

Fig. 3

Effects of fish oil on late PaO₂/FiO₂ in acute respiratory distress syndrome. CI, confidence interval; df, degrees of freedom; IV, instrumental variables; PUFA, polyunsaturated fatty acids; SD, standard deviation.

Fig. 4

Effects of fish oil on mechanical ventilation days in acute respiratory distress syndrome (ARDS). CI, confidence interval; df, degrees of freedom; IV, instrumental variables; PUFA, polyunsaturated fatty acids; SD, standard deviation.

Fig. 5

Effect of fish oil on gas exchange in older and newer trials. CI, confidence interval; df, degrees of freedom; IV, instrumental variables; PUFA, polyunsaturated fatty acids; SD, standard deviation.

Fig. 6

Effect of fish oil on gas exchange in acute respiratory distress syndrome: Sensitivity analysis restricted to oral/enteral administration. CI, confidence interval; df, degrees of freedom; IV, instrumental variables; PUFA, polyunsaturated fatty acids; SD, standard deviation.

Fig. 7

Effect of enteral fish oil on mortality in acute respiratory distress syndrome: Sensitivity analysis restricted to continuous infusion. CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel test; PUFA, polyunsaturated fatty acids.