Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury

Abstract

Context The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. Objective To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. Design, Setting, and Participants The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. Interventions Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. Main Outcome Measure Ventilator-free days to study day 28. Results The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=.02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P=.04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P=.02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P=.054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P=.11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P=.001). Conclusions Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. Trial Registration clinicaltrials.gov Identifier: NCT00609180

Definition and epidemiology of acute respiratory distress syndrome

“…While in adult population ARDS has shown a clear trend of decrease in mortality over the last decades, these results are not univocally confirmed in pediatric population, as reported with conflicting results in two recent meta-analysis of the literature (103,104). Over the last few years, different RCTs have proposed promising results in terms of ARDS mortality improvement (53,105,106). Unfortunately, this enthusiasm has to be well weighted in sight of the study design (107,108).…”

Nutrition in the ICU: proof of the pudding is in the tasting

“…While large audits including thousands of patients worldwide have shown that in daily practice, calorie and protein administration are well below current recommendations, varying between 1, 200 and 1,450 kcal/day and 0.5-0.8 g/ kg/day of protein [3], strong evidence regarding optimal energy and protein requirements as well as nutrient choices in various ICU conditions is not yet available. Most recent large trials focusing on one specific element of nutritional support, such as increased calories and/or protein, the use of supplemental parenteral nutrition, or high dose pharmaco-nutrients, have given confusing signals, failing to demonstrate any strong advantage [4][5][6][7][8][9]. This may leave the impression that most of the recommendations based on physiology do not lead to improved outcomes.…”

Metabolic and Nutrition Support in the Chronic Critical Illness Syndrome

“…101 Some studies have confirmed benefits of eicosapentaenoic acid (EPA), ␥-linolenic acid (GLA), and antioxidants in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). 102,103 In contrast, the recently published OMEGA study, 104 a randomized, double-blind, placebo-controlled trial of 272 patients with ALI, showed no benefit in clinical outcome and possible harm with enteral -3 fatty acids, GLA, and antioxidants, compared to an isocaloric control. The study population demonstrated significantly fewer ventilator-free days and more days with diarrhea.…”