Pharmaconutrition for Acute Lung Injury

A trial by the ARDS Clinical Trials Network of pharmaconutrition for acute lung injury1 was stopped early for futility – outcomes were worse in the intervention group that received the enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants. It had been hypothesised that the immunomodulatory effects of these supplements would provide clinical benefit in acute lung injury.

An accompanying editorial2 reports benefits of pharmaconutrition in other areas of critical care:

  • arginine-supplemented diets are associated with reduced infections and lengths of hospital stay in patients undergoing elective operations
  • glutamine-supplemented parenteral nutrition is associated with reduced infection and mortality in critically ill patients
  • antioxidant supplementation is associated with reduced mortality among critically ill patients with systemic inflammation.


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.


1. Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury
JAMA. 2011; 306:1574-1581

2. Pharmaconutrition in Acute Lung Injury
JAMA. 2011;306(14):1599-1600