Objectives

To determine if dietary supplementation of omega-3 (n-3) fatty acids, γ-linolenic acid and antioxidants to patients with acute lung injury would increase ventilator-free days to study day 28.

Background

Early acute lung injury (ALI) is characterized by neutrophilic lung inflammation, permeability,and intravascular and alveolar fibrin deposition. The type and inflammatory activity of eicosanoids liberated during inflammation depends on the membrane phospholipid composition: omega 6 (n-6) fatty acid arachidonate yields highly reactive and inflammatory dienoic prostaglandins and series 4 leukotrienes, whereas omega-3 (n-3) fatty acids favor production of less active and potentially anti-inflammatory trienoic prostaglandins and series 5 leukotrienes. Patients at risk of developing ALI have n-3 levels approximately 25% of normal and those with established ALI have n-3 levels as low as 6% of normal, suggesting a potential role for n-3 dietary supplementation in patients with ALI.

Three randomized controlled studies, conducted in patients with ALI or sepsis-induced respiratory failure, demonstrated an association between the administration of an enteral formula enriched in n-3 fatty acids, GLA, and antioxidants and improved oxygenation and respiratory physiology compared with an unenriched, high-fat formula. However, interpretation of these results is limited by the small sample sizes and as-treated analyses of only those patients who tolerated full enteral nutrition.

Participants

Patients with ALI requiring mechanical ventilation whose physicians intended to start enteral nutrition were eligible for inclusion. Specifically, patients had to be receiving mechanical ventilation, have a ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) of less than 300 (adjusted if altitude exceeded 1000 m), and have bilateral pulmonary infiltrates consistent with edema on chest radiograph without clinical evidence of left atrial hypertension. Severe chronic lung disease, ALI present greater than 48 hours, mechanical ventilation for longer than 72 hours, and inability to obtain consent were the most frequent exclusions.

Design

Patients were stratified by hospital and the presence of shock at baseline and then randomized to receive either twice-daily enteral supplementation of n-3 fatty acids, GLA, and antioxidants (n-3 supplement) or an isocaloric-isovolemic carbohydrate-rich control. Participants were also simultaneously randomized to a separate ongoing trial (the EDEN study) comparing low- vs full-calorie enteral nutrition in a 2 × 2 factorial design.

The n-3 or control supplement was administered enterally as twice-daily boluses of 120 mL beginning within 6 hours of randomization. Dosing continued until the earliest of 21 days, 48 hours of unassisted breathing, or extubation. The energy provided by the boluses supplemented that provided by each primary physician's choice of standard continuous non–n-3-enriched enteral formula. The rate of continuous enteral feeding was managed by a protocol with an algorithm for gastrointestinal intolerances. The supplement was administered even if enteral nutrition was interrupted, as long as the patient was tolerating enteral medications.

Conclusions

The study was stopped by the DSMB for futility at the first interim analysis after 143 patients had been randomized to receive the n-3 supplement and 129 to receive the isocaloric control. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days, intensive care unit–free days, and nonpulmonary organ failure-free days.

JAMA. 2011 Oct 12;306(14):1574-81.

Additional Details

Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.