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Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19 Is Typical of ARDS

Key findings

  • This case series characterizes 66 patients with COVID-19 respiratory failure who were managed with mechanical ventilation and established ARDS protocols
  • Upon initiation of mechanical ventilation, patients had a median PaO2:FiO2 of 182, dead space fraction of 0.45 and compliance of 35 mL per cm H2O, findings consistent with prior large cohorts of patients with ARDS
  • With prone positioning, improvements in oxygenation and compliance were consistent with prior studies of prone ventilation in early ARDS
  • After minimum follow-up of 30 days, mortality was 17% and most patients were successfully extubated and discharged from the ICU

Several early, small case series on patients with COVID-19 reported preserved respiratory system mechanics despite severe hypoxemia. This led some physicians to hypothesize that a significant proportion of COVID-19 respiratory failure is not the typical acute respiratory distress syndrome (ARDS) and warrants alternative management.

Physician-scientists Corey Hardin, MD, PhD, and Jehan Alladina, MD, and clinical fellow David R. Ziehr, MD, of the Division of Pulmonary and Critical Care Medicine at Massachusetts General Hospital, and colleagues refute this notion in a report on 66 patients published in The American Journal of Respiratory and Critical Care Medicine.

Study Subjects

The case series includes all 66 adult inpatients with respiratory failure related to COVID-19 who were intubated and admitted to an ICU at Mass General or Beth Israel Deaconess Medical Center between March 11, 2020, and March 30, 2020.


Management was at the discretion of the treating physician. Treatment guidelines at both hospitals recommended:

  • Ventilation with tidal volumes <6 mL/kg predicted body weight
  • Early consideration of prone ventilation for partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) <200
  • Conservative fluid management

Positive end-expiratory pressure (PEEP) was titrated per institutional protocols, which included use of the lower PEEP/higher FiO2 ARDS Network table, titration by best tidal compliance and esophageal manometry.

Respiratory Indices

On ICU admission, 56 patients (85%) met Berlin criteria for ARDS, mostly mild to moderate.

On intubation, median values were:

  • PEEP — 10 cm H2O
  • Plateau pressure — 21 cm H2O
  • Driving pressure — 11 cm H2O
  • Static compliance of the respiratory system — 35 mL per cm H2O
  • Estimated physiologic dead space ratio — 0.45

Similar parameters have previously been observed in large cohorts of ARDS patients.

Response to Prone Ventilation

Thirty-one patients underwent prone ventilation for a median of two sessions (range, 1–3), with a median of 18 hours per session:

  • In the supine position immediately prior to prone positioning — median PaO2:FiO2 was 150 and median compliance was 33 mL per cm H2O
  • After prone positioning — 232 and 36
  • After returning to supine position — 217 and 35
  • While supine 72 hours after initial prone positioning — 233 and 42


As of April 28, 2020, after a median follow-up of 34 days (range, 30-49):

  • Median duration of mechanical ventilation — 16 days
  • Tracheostomy — 14 patients (21%)
  • Successfully extubated — 41 patients (62%)
  • Discharge from ICU — 50 patients (76%)
  • Deaths — 11 (17%)


These findings differ from those in the early series that described near-normal respiratory system compliance and lack of recruitability in patients with COVID-19 respiratory failure. This study provides pathophysiologic justification for the use of established ARDS therapies in COVID-19, including low tidal volume and early prone ventilation.

days median duration of mechanical ventilation in patients with COVID-19 respiratory failure

of patients with COVID-19 respiratory failure successfully extubated

of patients with COVID-19 respiratory failure discharged from ICU

mortality in patients with COVID-19 respiratory failure

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