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Ann Am Thorac Soc. 2019 Mar;16(3):356-362. doi: 10.1513/AnnalsATS.201807-459OC.

Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure.

Collaborators (170)

Hayden D, Morse RE, Oldmixon CF, Ringwood NJ, Steingrub JS, De Souza L, Kardos C, Kozikowski L, Tidswell M, Hou PC, Aisiku IP, Baron RM, Fredenburgh LE, Gandee ZA, Massaro AF, Moreno AH, Shao W, Seethala RR, Riker RR, Macleaod A, Hill NS, Bacong V, Chweich H, Devlin J, Garpestad E, Talmor D, Shapiro N, Banner-Goodspeed V, Keenawinna L, Muller LN, Pinkhasova T, Bajwa E, Filbin M, Hibbert KA, Holland C, Arsenault PA, Sigel P, Jones A, Spurzem JR, Cruise M, Matthay MA, Liu KD, Belzer AG, Calfee C, Daniel BM, Deiss TJ, Gotts JE, Hendey GW, Anklesaria Z, Chang SY, Lewis S, Mehta I, Qadir N, Sharif J, Levitt J, Vojnik R, Albertson TE, Adams JY, Juarez M, Morrissey B, Pearson S, Almasri E, Blaauw JM, Ginde A, Moss M, Finck L, Higgins C, McKeehan J, Mills E, Tompkins A, Douglas IS, Haukoos J, Hiller T, Hopkins E, Oaks JL, Overdier K, Schmidt M, Van Pelt DC, Tashkin JS, Finigan JH, Lyn-Kew K, Paterson RD, Lemos-Filho L, Park PK, Chen T, Hanna S, Nelson K, DiGiovine B, Rivers EP, Rubino S, Chen T, Hope AA, Munoz ME, Gummadi S, Fuster D, Ceusters D, Lopez B, Gummadi S, Richardson LD, Fass E, Goel NN, Richman L, Schneider G, Hite RD, Duggal A, Hastings A, Terndrup TE, Bolton LL, Exline MC, Robart E, Frey J, Stiffler K, Coury ML, Norton D, Roads T, Studer A, Angus DC, Yealy DM, Gilchrist EG, Huang DT, Young ML, Campbell N, Muller A, Promes SB, Hough C, Caldwell ES, Katsandres SC, Khan A, Haberkorn S, OMahony SD, Boisjolie C, Files DC, Miller CD, Elliott SB, Flores LS, Doroshenko J, Futrell W, Harper E, Phelps S, Lockwood R, Wright PE, Becker L, Enfield KB, Kadl A, Marshall MH, Sochor MR, de Wit M, Hamman S, Grissom CK, Allen TL, Brown SM, Lanspa MJ, Aston V, Peterson J, Miller III RR, Clemmer TP, Pies S, Harris ES, Plante A, Harris DL, Nielsen D, Woodward WE, Rice TW, Self WH, Baughman AH, Hayes M, Mogan S, Semler MW, Janz DR, Lauto PO.

Author information

1 Intermountain Medical Center and.
2 University of Utah, Salt Lake City, Utah.
3 Montefiore Healthcare Center, Albert Einstein College of Medicine, Bronx, New York.
4 Massachusetts General Hospital, Harvard University, Boston, Massachusetts.
5 Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
6 Brigham and Women's Hospital, Harvard University, Boston, Massachusetts.
7 Hospital Israelita Albert Einstein, São Paulo, Brazil.
8 University of Michigan, Ann Arbor, Michigan.
9 University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
10 University of Washington, Seattle, Washington.
11 Johns Hopkins University School of Medicine, Baltimore, Maryland.
12 University of California, San Francisco, San Francisco, California.
13 University of Massachusetts Medical School-Baystate, Springfield, Massachusetts.
14 Wake Forest Baptist Health, Winston Salem, North Carolina.
15 LDS Hospital, Salt Lake City, Utah.
16 University of California, Los Angeles, Los Angeles, California.
17 Icahn School of Medicine at Mount Sinai, New York, New York; and.
18 Baystate Medical Center, Springfield, Massachusetts.



Low-tidal volume ventilation (LTVV; 6 ml/kg) benefits patients with acute respiratory distress syndrome and may aid those with other causes of respiratory failure. Current early ventilation practices are poorly defined.


We observed patients with acute respiratory failure to assess the feasibility of a pragmatic trial of LTVV and to guide experimental design.


We prospectively enrolled consecutive patients with acute respiratory failure admitted to intensive care units expected to participate in the proposed trial. We collected clinical data as well as information on initial and daily ventilator settings and inpatient mortality. We estimated the benefit of LTVV using predictive linear and nonlinear models. We simulated models to estimate power and feasibility of a cluster-randomized trial of LTVV versus usual care in acute respiratory failure.


We included 2,484 newly mechanically ventilated patients (31% with acute respiratory distress syndrome) from 49 hospitals. Hospital mortality was 28%. Mean initial tidal volume was 7.1 ml/kg predicted body weight (95% confidence interval, 7.1-7.2), with 78% of patients receiving tidal volumes less than or equal to 8 ml/kg. Our models estimated a mortality benefit of 0-2% from LTVV compared with usual care. Simulation of a stepped-wedged cluster-randomized trial suggested that enrollment of 106,361 patients would be necessary to achieve greater than 90% power.


Use of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible. A rapid observational study and simulations to model anticipated power may help better design trials.


acute respiratory distress syndrome; low-stretch ventilation; low–tidal volume ventilation; lung-protective ventilation; mechanical ventilation

[Available on 2020-03-01]

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