Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome

Objectives: Recent studies in animal models of sepsis-induced acute respira tory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosap entaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA +GLA), and antioxidants improves lung microvascular permeability, oxygenati on, and cardiopulmonary function and reduces proinflammatory eicosanoid syn thesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may im prove oxygenation and clinical outcomes in patients with ARDS. Design: Prospective, multicentered, double-blind, randomized controlled tri al. Setting: Intensive care units of five academic and teaching hospitals in th e United States. Patients: We enrolled 146 patients with ARDS (as defined by the American-Eu ropean Consensus Conference) caused by sepsis/pneumonia, trauma, or aspirat ion injury in the study. Interventions: Patients meeting entry criteria were randomized and continuo usly tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. Measurements and Main Results: Arterial blood gases were measured, and vent ilator settings were recorded at baseline and study days 4 and 7 to enable calculation of Pao(2)/Fio(2) a measure of gas exchange. Pulmonary neutrophi l recruitment was assessed by measuring the number of neutrophils and the t otal cell count in bronchoalveolar lavage fluid at the same time points. Cl inical outcomes were recorded. Baseline characteristics of 98 evaluable pat ients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavage s revealed significant decreases (similar to 2.5-fold) in the number of tot al cells and neutrophils per mt of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant impro vements in oxygenation (Pao(2)/Fio(2)) from baseline to study days 4 and 7 with lower ventilation variables (Ro,, positive end-expiratory pressure, an d minute ventilation) occurred in patients fed EPA+GLA compared with contro ls. Patients fed EPA+GLA required significantly fewer days of ventilatory s upport (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with contro ls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control pa tients developed a new organ failure during the study (p = .015). Conclusions: The beneficial effects of the EPA+GLA diet on pulmonary neutro phil recruitment, gas exchange, requirement for mechanical ventilation, len gth of intensive care unit stay, and the reduction of new organ failures su ggest that this enteral nutrition formula would be a useful adjuvant therap y in the clinical management of patients with or at risk of developing ARDS .