Kusum S Mathews1,2, Howard Soh1, Shahzad Shaefi3, Wei Wang4, Sonali Bose1, Steven Coca5, Shruti Gupta6, Salim S Hayek7, Anand Srivastava8, Samantha K Brenner9,10, Jared Radbel11, Adam Green12, Anne Sutherland13, Amanda Leonberg-Yoo14, Alexandre Shehata15, Edward J Schenck16, Samuel A P Short17, Miguel A Hernán18,19,20, Lili Chan5, David E Leaf6. 1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 2. Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 3. Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA. 4. Department of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA. 5. Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 6. Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA. 7. Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor, MI. 8. Division of Nephrology and Hypertension, Department of Medicine, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. 9. Department of Internal Medicine, Hackensack Meridian School of Medicine, Nutley, NJ. 10. Department of Internal Medicine, Heart & Vascular Hospital, Hackensack Meridian Health, Hackensack University Medical Center, Hackensack, NJ. 11. Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. 12. Division of Critical Care Medicine, Department of Medicine, Cooper University Health Care, Camden, NJ. 13. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ. 14. Division of Renal-Electrolyte and Hypertension, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 15. Department of Medicine, Hackensack Meridian Health Mountainside Medical Center, Glen Ridge, NJ. 16. Division of Pulmonary and Critical Care Medicine, Department of Medicine Weill Cornell Medicine, New York, NY. 17. Larner College of Medicine, University of Vermont, Burlington, VT. 18. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 19. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA. 20. Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston, MA.
Abstract
OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.
OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.
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