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A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury*

Stapleton, Renee D. MD, PhD; Martin, Thomas R. MD; Weiss, Noel S. MD, DrPH; Crowley, Joseph J. MD; Gundel, Stephanie J. RD; Nathens, Avery B. MD, PhD, MPH; Akhtar, Saadia R. MD, MSc; Ruzinski, John T. BS; Caldwell, Ellen MS; Curtis, J. Randall MD, MPH; Heyland, Daren K. MD, MSc; Watkins, Timothy R. MD; Parsons, Polly E. MD; Martin, Julie M. RD, MS; Wurfel, Mark M. MD, PhD; Hallstrand, Teal S. MD, MPH; Sims, Kathryn A. MN, RN; Neff, Margaret J. MD, MSc

doi: 10.1097/CCM.0b013e318218669d
Clinical Investigations

Objectives: Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought to determine whether enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with acute lung injury.

Design: Phase II randomized controlled trial.

Setting: Five North American medical centers.

Patients: Mechanically ventilated patients with acute lung injury ≥18 yrs of age.

Interventions: Subjects were randomized to receive enteral fish oil (9.75 g eicosapentaenoic acid and 6.75 g docosahexanoic acid daily) or saline placebo for up to 14 days.

Measurements and Main Results: Bronchoalveolar lavage fluid and blood were collected at baseline (day 0), day 4 ± 1, and day 8 ± 1. The primary end point was bronchoalveolar lavage fluid interleukin-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum eicosapentaenoic acid concentration (p < .0001). However, there was no significant difference in the change in bronchoalveolar lavage fluid interleukin-8 from baseline to day 4 (p = .37) or day 8 (p = .55) between treatment arms. There were no appreciable improvements in other bronchoalveolar lavage fluid or plasma biomarkers in the fish oil group compared with the control group. Similarly, organ failure score, ventilator-free days, intensive care unit-free days, and 60-day mortality did not differ between the groups.

Conclusions: Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with acute lung injury, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof-of-concept studies evaluating new treatments for acute lung injury.

From the Department of Medicine (RDS, PEP, JMM), Division of Pulmonary and Critical Care Medicine, University of Vermont College of Medicine, Burlington, VT; the Department of Medicine (TRM, SJG, JTR, EC, JRC, TRW, MMW, TSH, KAS, MJN), Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA; the Department of Epidemiology (NSW), University of Washington, Seattle, WA; St Alphonsus Regional Medical Center (JJC), Boise, ID; the Department of Surgery (ABN), Division of General Surgery, University of Toronto, Toronto, Ontario, Canada; St Luke's Boise Medical Center (SRA), Boise, ID; the Department of Medicine (DKH), Queen's University, Kingston, Ontario, Canada; and Puget Sound Blood Center (TRW), Research Division, Seattle, WA.

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This research was supported by an American Thoracic Society/Acute Respiratory Distress Syndrome Foundation Award, an American Society for Parenteral and Enteral Nutrition Rhoads Research Foundation Award, and National Institutes of Health Grants 1P50HL073996, 8K12RR023265, and 5P20RR015557. Nordic Naturals also donated the fish oil used in this trial but had no input into study design, study conduct, data management, or publication.

The authors have not disclosed any potential conflicts of interest.

This research was performed at the University of Washington, University of Vermont, University of Toronto, and St Alphonsus Regional Medical Center in Boise, ID.

For information regarding this article, E-mail: renee.stapleton@uvm.edu

No reprints will be ordered.

© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins