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N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19.

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

Collaborators (269)

Steingrub JS, Tidswell M, Kozikowski L, De Souza L, Kardos C, Hou PC, Aisiku IP, Baron RM, Massaro AF, Seethala RR, Fredenburgh LE, Gandee ZA, Israelyan A, Riker RR, Macleaod A, May T, Seder D, Van der Kloot TE, Hill NS, Bacong V, Chweich H, Garpestad E, Schweish O, Talmor D, Shapiro N, Banner-Goodspeed V, Jinadasa S, Brenes Bastos A, Bajwa E, Filbin MR, Hibbert KA, Holland C, Brait K, Arsenault PA, Sigel P, Jones AE, Spurzem JR, Puskarich M, Hope Cruise M, Kolb JJ, Patki D, Matthay MA, Liu KD, Calfee CS, Gotts JE, Daniel BM, Belzer A, Hendey GW, Chang SY, Qadir N, Garber B, Guo S, Lewis S, Sharif J, Levitt J, Rogers A, Vojnik R, Asuni AT, Albertson TE, Adams JY, Juarez M, Morrissey B, Pearson S, Almasri E, Blaauw JM, Hughes A, Sousa K, Ginde A, Moss M, Finck L, Higgins C, McKeehan J, Douglas IS, Haukoos J, Hiller T, Hopkins E, Oaks JL, Overdier K, Schmidt M, Van Pelt DC, Tashkin JS, Reischel J, Finigan JH, Lyn-Kew K, Paterson RD, Lemos-Filho L, Hyzy RC, Park PK, Nelson K, Co IN, McSparron JI, Chen T, Hanna S, Olbrich N, DiGiovine BM, Rivers EP, Day J, Gill J, Gardner Gray J, Hurst G, Jayaprakash N, Kathrina Jaehne A, Rubino S, Swiderek J, Pflaum J, Williams M, Kapoor R, Ellender T, Gutteridge D, Nash J, Ng Gong M, Hope AA, Chen JT, Gummadi S, Fuster D, Munoz ME, Lopez B, Richardson LD, Acquah S, Mathews K, Richman L, Goel NN, Li N, Schneider G, Clesca C, Massenburg NS, Hite RD, Duggal A, Hastings A, Mehkri O, Hanane T, Rice A, Terndrup TE, Exline MC, Englert J, Robart E, Pannu S, Ali NA, Frey JA, Stiffler KA, Norton D, Roads T, Studer A, Hudock K, Angus DC, Yealy DM, Huang DT, McVerry BJ, Scholl D, Gacka C, Thangudu P, Padmanabhan R, Balakumar V, McComb JG, Fazio P, Stefanick M, Donadee CL, Siedsma M, Murugan R, Jockers A, Campbell N, Muller A, Promes SB, Hough C, Robinson BRH, Johnson NJ, Gundel S, Katsandres SC, Ungar AM, Cardey J, Poon T, Dean S, Haberkorn S, Haq E, Kea B, Schreiber MA, Khan A, O'Mahony SD, Boisjolie C, Files DC, Miller CD, Bakhru R, Flores LS, Gibbs K, LaRose M, Purcell L, Wright PE, Enfield KB, Sochor M, Kadl A, Marshall M, Morris PE, Dhar S, Montgomery-Yates A, Sturgill J, Pasha S, de Wit M, Hamman S, Grissom CK, Bledsoe J, Allen T, Kumar N, Brown SM, Hopkins M, Lanspa M, Peltan I, Hirshberg E, Orme J, Merrill M, Montgomery Q, Brown K, Armbruster B, Aston V, Clemmer T, Knight K, Shepherd A, Sillito C, Kerwin B, Paine R, Harris E, Middleton E, Plante A, Harris D, Woodward W, Nielsen D, Rice TW, Self WH, Semler MW, Hayes M, Mogan S, Baughman A, Janz DR, Lauto P, Moore MM, deBoisblanc BP, Hunt JP, Mooney JL, Jolley SE, Schoenfeld DA, Thompson BT, Lee KT, Ulysse C, Oldmixon CF, Ringwood NJ, Pedrin JR, Morse RE, Hayden D, Bienstock K, Blaisdell CJ, Harabin AL, Reineck LA, Ghofrani P, Waclawiw MA, Weinmann G, Morrison LJ, Cairns CB, Carson S, Courtney DM, Gillespie MN, Kryscio RJ, Parsons P, Christie JD, Hall JR, Horton NJ, Kline JA, Levy M, Siegel M, Stiell I, Zoloth LS.

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The affiliations of the members of the writing committee are as follows: the Departments of Medicine (M.M.) and Emergency Medicine (A.A.G.), University of Colorado School of Medicine, Aurora; the Departments of Critical Care Medicine (D.T.H., D.C.A.) and Emergency Medicine (D.M.Y.), University of Pittsburgh School of Medicine, Pittsburgh; the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (R.G.B.); the Interdepartmental Division of Critical Care Medicine, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto (N.D.F.); the Department of Medicine, Montefiore Hospital, New York (M.N.G.); the Department of Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City (C.K.G.); the Department of Medicine, University of Washington, Seattle (S.G., C.L.H.); the Biostatistics Center (D.H.), the Department of Medicine (B.T.T.), and the PETAL Network Clinical Coordinating Center (C.A.U.), Massachusetts General Hospital, the Department of Emergency Medicine, Division of Emergency Critical Care Medicine, Brigham and Women's Hospital (P.C.H.), and the Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center (D.T.) - all in Boston; the Department of Critical Care, Respiratory Institute, Cleveland Clinic, Cleveland (R.D.H.); the Department of Medicine, University of Michigan and Veterans Affairs Center for Clinical Research, Ann Arbor (T.J.I.); the Department of Medicine, Oregon Health and Science University, Portland (A.K.); and the Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco (K.D.L.).



The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.


We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days.


The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months.


Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE number, NCT02509078.).

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