Pascal L Langlois1, Fréderick D'Aragon2, Gil Hardy3, William Manzanares4. 1. Department of Anesthesiology and Reanimation, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada. Electronic address: Pascal.laferriere-langlois@usherbrooke.ca. 2. Department of Anesthesiology and Reanimation, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada. 3. Ipanema Research Trust, Auckland, New Zealand. 4. Department of Critical Care, Intensive Care Unit, University Hospital, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
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.
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 ARDSpatients, 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 ARDSpatients 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 ARDSpatients. 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 illpatients 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.
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