Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury

JAMA. 2011 Oct 12;306(14):1574-81. doi: 10.1001/jama.2011.1435. Epub 2011 Oct 5.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Lung Injury / complications
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / mortality
  • Adult
  • Aged
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use*
  • Biomarkers / blood
  • Dietary Supplements / adverse effects
  • Docosahexaenoic Acids / adverse effects
  • Docosahexaenoic Acids / blood
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / adverse effects
  • Eicosapentaenoic Acid / blood
  • Eicosapentaenoic Acid / therapeutic use*
  • Enteral Nutrition
  • Female
  • Humans
  • Inflammation / drug therapy
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Pneumonia / complications
  • Sepsis / complications
  • Survival Analysis
  • Treatment Outcome
  • Ventilator Weaning*
  • gamma-Linolenic Acid / adverse effects
  • gamma-Linolenic Acid / therapeutic use*

Substances

  • Antioxidants
  • Biomarkers
  • Docosahexaenoic Acids
  • gamma-Linolenic Acid
  • Eicosapentaenoic Acid

Associated data

  • ClinicalTrials.gov/NCT00609180