临床时讯 ＞ 临床研究
JAMA. 2011 Oct 12;306(14):1574-81. Epub 2011 Oct 5.
Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.
Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P; NHLBI ARDS Clinical Trials Network.
Collaborators: Hudson L, Hough C, Neff M, Sims K, Watkins T, Steingrub J, Tidswell M, DeSouza L, Kardos C, Kozikowski L, Kozikowski K, Guntupalli K, Bandi V, Pope C, Brower R, Fessler H, Hager D, Mendez-Tellez P, Oakjones K, Needham D, Sevransky J, Workneh A, Han S, Murray S, Shanholtz C, Netzer G, Rock P, Sampaio A, Titus J, Sloane P, Beck T, Highfield H, Herr D, Lee B, Bolouri N, Wiedemann HP, Ashton RW, Culver DA, Frederick T, Komara JJ, Guzman JA, Reddy AJ, Hejal R, Andrews M, Haney D, Connors AF, Lasalvia S, Thornton JD, Warren EL, Moss M, Benson A, Burnham E, Clark B, Gray L, Higgins C, Maloney BJ, Mealer M, Frankel S, Bost T, Dennen P, Hodgin K, Douglas I, Overdier K, Thompson K, Wolken R, MacIntyre N, Brown L, Cox C, Gentile M, Govert J, Knudsen N, Carson S, Chang L, Lanier J, Wheeler AP, Bernard GR, Hays M, Mogan S, Rice TW, Hite RD, Morris PE, Harvey A, Ragusky M, Bender K, Wright P, Gross S, McLean J, Overton A, Truwit J, Enfield K, Marshall M, Clemmer T, Tanaka R, Weaver L, Morris A, Ahmed A, Austin A, Dean N, Grissom C, Fitzpatrick A, Hirshberg E, Kumar N, Miller R, Orme J, Pandita S, Schreiber G, Struck L, Thomas F, Thomsen G, VanBoerum D, White T, Zenger M, Dienhart D, Nelson P, Goddard M, Krueger J, Napoli L, Lawton C, Baughman J, Fujii T, Hanselman D, Hoffman T, Kerwin B, Kim P, Leung F, Sundar K, Alward W, Campbell E, Eckley D, Hill T, Ludwig K, Nielsen D, Pearce M, Matthay MA, Calfee C, Daniel B, Eisner M, Garcia O, Johnson E, Kallet R, Kordesch K, Liu K, Zhou H, Peterson MW, Blaauw J, Albertson T, Vlastelin E, Hubmayr R, Brown D, Gajic O, Hinds R, Holets S, Kor DJ, Passe M, deBoisblanc B, Lauto P, Romaine C, Meyaski G, Hunt J, Marr A, Brierre S, LeBlanc C, Taylor D, Jain S, Seoane L, Simeone F, Fearon J, Duchesne J, Schoenfeld D, Aquino M, Dong N, Dorer D, Guha M, Hammond E, Lavery N, Lazar P, Molina I, Morse R, Oldmixon C, Rawal B, Ringwood N, Shui A, Smoot E, Thompson BT, Harabin A, Bredow S, Waclawiw M, Weinmann G, Spragg RG, Slutsky A, Levy M, Markovitz B, Petkova E, Weijer C, Sznajder J, Begg M, Israel E, Lewis J, McClave S, Parsons P.
Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.
OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.
DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.
INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.
MAIN OUTCOME MEASURE: Ventilator-free days to study day 28.
RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).
CONCLUSIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609180.
JAMA. 2011 Oct 12;306(14):1599-600.
Pharmaconutrition in acute lung injury.
Cook DJ, Heyland DK.
During the last decade, there has been a major conceptual shift in thinking about artificial nutrition provided to critically ill patients. Because of its modulating effect on pathophysiology and emerging evidence about potential effects on clinical outcomes, nutrition is now considered "therapy" and not simply "supportive care." For example, arginine-supplemented diets are associated with reduced infections and lengths of hospital stay in patients undergoing elective operations, glutamine-supplemented parenteral nutrition is associated with reduced infection and mortality in critically ill patients, and antioxidant supplementation is associated with reduced mortality among critically ill patients with systemic inflammation. The new model of "pharmaconutrition" calls for trials examining the dose, route, timing, and duration of each intervention, focusing on whether the intervention is designed to restore an existing deficiency, reduce ongoing loss of an expended substrate, and/or provide supratherapeutic exposure.