Objectives: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA + GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA + GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS.
Design: Prospective, multicentered, double-blind, randomized controlled trial.
Setting: Intensive care units of five academic and teaching hospitals in the United States.
Patients: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study.
Interventions: Patients meeting entry criteria were randomized and continuously 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 ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases ([similar]2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA + GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO (2/FIO)2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA + GLA compared with controls. Patients fed EPA + GLA required significantly fewer days of ventilatory support (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 controls. Only four of 51 (8%) patients fed EPA + GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015).
Conclusions: The beneficial effects of the EPA + GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS. (Crit Care Med 1999; 27:1409-1420)
The Enteral Nutrition in ARDS Study Group.
From the Pulmonary and Critical Care Division (Drs. Gadek and Pacht), Ohio State University Medical Center, Columbus, OH; Medical Nutrition Research & Development (Drs. DeMichele, Wennberg, and Nelson), Ross Products Division, Abbott Laboratories, Columbus, OH; Department of Anesthesiology (Dr. Karlstad), University of Tennessee Medical Center at Knoxville, Knoxville, TN; Division of Pulmonary and Critical Care Medicine (Dr. Donahoe), University of Pittsburgh Medical Center, Pittsburgh, PA; Division of Pulmonary and Critical Care Medicine (Drs. Albertson and Hoozen), University of California-Davis Medical Center, Sacramento, CA; SCIREX Corporation (Dr. Noursalehi) Bloomingdale, IL; and the Mayo Clinic, Rochester, MN.
The following additional physicians, study coordinators, clinical research associates, analytical scientists, and statisticians participated in the Enteral Nutrition in ARDS Study Group: Ohio State University Medical Center, Columbus, OH, Jan Drake, Pat Farmer, Judy Hart, Carol Koetting-Freeman, Nancy Rague; University of Tennessee Medical Center at Knoxville, Knoxville, TN, Ed Cruz, MD, Cathy Mucenski, MD, Steve Morris, MD, Kathy Gardener, MD, Mary Moore, Jay Whelan, PhD, Carolyn Snider; Department of Anesthesiology, Mayo Clinic, Rochester, MN, Michael Murray, MD, PhD, Barry Harrison, MD, Matt Kumar, MD, Anita Baumgartner, Lynn Harstad; University of Pittsburgh Medical Center, Pittsburgh, PA, Anne Crory; University of California-Davis Medical Center, Sacramento, CA, Ellen Vlastelin, Roblec Allen, MD, R. Steven Tharratt, MD; SCIREX Corporation, Bloomingdale, IL, Nick Satow, PhD, Yinpu Chen; Ross Products Division, Abbott Laboratories, Columbus, OH, Mark Hill, Theresa Lee, Anne Rudick, Timothy Gregory, PhD, Mark McCamish, PhD, MD.
Supported, in part, by a grant from Ross Products Division, Abbott Laboratories.
Address requests for reprints to: James E. Gadek, MD, Pulmonary and Critical Care Division, Ohio State University Medical Center, N325 Means Hall, 1654 Upham Drive, Columbus, OH 43210-1228.