Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study


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14 Scopus citations


Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? Study Design and Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and PaO2 to FIO2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. Results: A total of 2,466 patients were enrolled. Median baseline PaO2 to FIO2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. Trial Registry:; No.: NCT03021824; URL:

Original languageEnglish
Pages (from-to)1304-1315
Number of pages12
Issue number4
StatePublished - Oct 2021

Bibliographical note

Funding Information:
Author contributions: The study was designed by N. Q. P. K. P. R. R. B. and M. N. G. Data was acquired from individual sites by the following investigators: N. Q. R. R. B. C. L. H. M. J. L. V. M. B.-G. J.-T. C. S. G. D. G. M. W. S. N. H. J. K. A. D. A. K. K. R. K. A. K. S. Y. C. J. E. T. H. L. A. J. M. L. J. M. M. P. E. M. A. G. I. K. L. M. T. R. S. S. A. M. E. D. J. D. A. M. K. E. S. W. B. A. T. P. K. G. and S. H. R. R. B. and M. L. C. had full access to all of the data in the study and performed the data analyses. The initial manuscript was drafted by N. Q. and P. K. P. All authors provided critical input into manuscript revisions. P. K. P. is the guarantor of the paper. Financial/nonfinancial disclosures: None declared. ∗Severe ARDS: Generating Evidence (SAGE) Study Investigators (alphabetical, by center): Baystate Medical Center: Jay S Steingrub, Mark Tidswell; Beth Israel Deaconess Medical Center: Valerie M Banner-Goodspeed, Kristin Brierley, Julia L Larson, Ariel Mueller, Tereza Pinkhasova, Daniel Talmor; Brigham and Women's Hospital: Imoigele Aisiku, Rebecca Baron, Lauren Fredenburgh, Alissa Genthon, Peter Hou, Anthony Massaro, Raghu Seethala; Cleveland Clinic: Abhijit Duggal, Duncan Hite, Ashish K Khanna; Columbia University: Daniel Brodie, Irene K Louh, Briana Short; Duke University Medical Center: Raquel Bartz, Mary L Cooter, Jordan C Komisarow; East Carolina University: Anupama Tiwari; Emory University: William Bender, James Blum; Grady Memorial Hospital: Annette Esper, Greg S. Martin; Harborview Medical Center: Eileen Bulger, Catherine L Hough, Anna Ungar; Intermountain Medical Center: Samuel M Brown, Colin K Grissom, Eliotte L Hirshberg, Michael J Lanspa, Ithan D Peltan; Johns Hopkins University: Roy G Brower, Sarina K Sahetya, R Scott Stephens; Mayo Clinic Florida: Pramod K Guru; Mayo Clinic Rochester: John K Bohman, Hongchuan Coville, Ognjen Gajic, Rahul Kashyap, John C O'Horo; Montefiore Medical Center: Jorge-Bleik Ataucuri-Vargas, Jen-Ting Chen, Michelle N Gong, Fiore Mastroianni; Northwell Health System: Negin Hajizadeh, Jamie Hirsch, Michael Qui, Molly Stewart; Oregon Health Sciences University: Akram Khan, Ebaad Haq, Makrina Kamel, Olivia Krol, Kimberly Lerner; Regions Hospital: David J Dries, John Marini; St. Agnes Hospital: Valentina Chiara Bistolfi Amaral, Anthony Martinez; St. Joseph's Medical Center: Harry L Anderson, III, Jill Brown, Michael Brozik, Heidi Kemmer, Janet Obear; Temple University: Nina Gentile, Kraftin E Shreyer; University of Arizona - Banner Health: Charles Cairns, Cameron Hypes, Josh Malo, Jarrod Mosier, Bhupinder Natt; University of California Los Angeles: Steven Y Chang, Scott Hu, Ishan Mehta, Nida Qadir; University of Cincinnati: Richard Branson, Dina Gomaa, Betty Tsuei; University of Kentucky: Sanjay Dhar, Ashley Montgomery-Yates, Peter Morris; University of Michigan: Tina Chen, Sinan Hanna, Pauline K Park, Michael W Sjoding; University of Southern California: Alfredo Lee Chang, Perren Cobb, Janice M. Liebler; University of Utah: Estelle Harris, Nate Hatton, Gia Lewis, Stephen McKellar, Sanjeev Raman, Joseph Tonna; University of Washington: Ellen Caldwell, Sarah Dean, Shewit Giovanni. Additional information: The e-Appendixes, e-Figure, and e-Tables can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Publisher Copyright:
© 2021


  • ARDS
  • corticosteroids
  • extracorporeal membrane oxygenation
  • mechanical ventilation
  • neuromuscular blockade
  • prone positioning

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine


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