A number of previous studies, including three randomized controlled trials, demonstrated an association with improved outcomes in patients with acute lung injury (ALI) or sepsis-induced respiratory failure when fatty acid supplements were administered. In the October issue of the Journal of the American Medical Association, Todd Rice, MD, MS, and investigators from the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, reported the results of the OMEGA study, a multicenter, randomized, double-blind, placebo-controlled trial.  The investigators hypothesized that enteral supplementation with n-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid), gamma-linolenic acid (GLA) and an antioxidant supplement would lead to improved outcomes in patients with ALI.

Of 2,778 patients screened, 272 patients mechanically ventilated patients with ALI were randomized to either placebo (n=129; isocaloric carbohydrate-rich enteral feeds) or experimental (n=143; n-3 fatty acids, GLA, and antioxidant supplement) groups.  The primary endpoint was ventilator-free days.  Secondary endpoints included 60-day mortality, plasma levels of interleukins and leukotrienes, development of new infections, ICU- and organ-failure free days, and frequency of gastrointestinal intolerance.

The experimental group was reasonably balanced against the control group, although there were some differences.  Patients in the experimental group had higher minute ventilation (p=0.04), greater fluid intake (p=0.09), and higher vasopressor use at the time of enrollment.  Multiple logistic regression was used to control for baseline shock and other mortality-predicting covariates.

The study was terminated early by the data safety monitoring board after an interim analysis indicated worse outcomes in the experimental group.  Patients in the experimental group had fewer ventilator-free days than the placebo group (14.0 [SD 11.1] vs. 17.2 [10.2], p=0.02).  The experimental group also had fewer ICU-free days (14.0 vs 16.7, p=0.04), and higher unadjusted mortality (26.6% vs 16.3 %, p=0.054).  When mortality was adjusted for baseline covariates, no statistically significant different was observed between groups (p=0.11). The experimental group had fewer organ failure-free days (12.3 vs 15.5, p=0.02).

The findings in this study are incongruent with prior work in this area, and this may be attributed to a lower overall ALI mortality (21.7%) than observed in previous n-3 fatty acid studies, a slight imbalance in baseline covariates that might have benefitted the control group, and the use of low tidal volumes in both study groups.  Additionally, the use of different enteral preparations and ventilator protocols in earlier studies might have biased results in favor of n-3 fatty acids.

The authors concluded that enteral supplementation of fatty acids, GLA, and antioxidants in patients with ALI does not improve outcomes and may be harmful.

Concise Critical Appraisal is a regular feature authored by SCCM member Samuel M. Galvagno Jr., DO. Each installment highlights journal articles most relevant to the critical care practitioner.