Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study

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Salient features:

This article focuses on:

  • Methods
  • Population and Setting
  • Data Collection and Definitions
  • Statistical analysis
  • Results
  • Demographic and Clinical Characteristics
  • Respiratory Failure and Respiratory System Indices
  • Response to Prone Ventilation
  • Outcomes
  • Discussion
  • Limitations

Detailed summary:


Population and Setting

  • Adult inpatients with SARS-CoV-2 infection and respiratory failure managed with invasive mechanical ventilation at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) were studied between March 11 and March 30, 2020.
  • Clinical management occurred at the discretion of the treating physician.

Hospital treatment guidelines recommended ventilation with tidal volumes less than 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, and conservative fluid management.

  • Positive end-expiratory pressure (PEEP) was titrated per institutional protocols and included use of the lower PEEP / higher FiO2 ARDS network table, titration by best tidal compliance, and esophageal manometry.
  • Routine use of high-flow nasal cannula or non-invasive positive pressure ventilation was not recommended.

Data Collection and Definitions

  • Data was collected from the electronic medical record.
  • Physiological dead space fraction was estimated using the unadjusted Harris-Benedict estimate of resting energy expenditure and the rearranged Weir equation for CO2 production.
  • Ventilatory ratio was also calculated.

Statistical Analysis

  • Descriptive statistics was used to summarize clinical data.
  • Results are reported as medians and interquartile ranges (IQR).
  • We report all available data without imputation. Analysis was performed with GraphPad Prism v7.0 software.


Demographic and Clinical Characteristics

  • From March 11 to March 30, 2020, 66 patients with laboratory-confirmed COVID19 were intubated and admitted to MGH and BIDMC ICUs.
  • Median age was 58 years (range, 23-87) and 43 patients (65%) were male.
  • Eight patients (12%) had preexisting pulmonary disease and 22 patients (34%) were current or former smokers.

Respiratory Failure and Respiratory System Indices

  • On ICU admission, 56 patients met Berlin criteria for ARDS and most patients had mild to moderate ARDS.
  • On intubation, median PEEP was 10 cm H2O (IQR, 8-12), plateau pressure was 21 cm H2O (IQR, 19-26), and driving pressure was 11 cm H2O (IQR, 9- 12).
  • Static compliance of the respiratory system was 35 mL per cm H2O (IQR, 30-43). Estimated physiologic dead space ratio was 0.45 (IQR, 0.38-0.58).

Response to Prone Ventilation

  • Of the 31 patients who underwent prone ventilation, median PaO2:FiO2 in the supine position was 150 (IQR, 125-183) and compliance was 33 mL per cm H2O (IQR, 26-46) immediately prior to prone positioning.
  • After prone positioning, PaO2:FiO2 increased to 232 (IQR, 174-304) and compliance increased to 36 mL per cm H2O (IQR, 33-44).
  • After returning to the supine position, PaO2:FiO2 was 217 (IQR, 149-263) and compliance was 35 mL per cm H2O (IQR 31-41).
  • Seventy-two hours after initial prone ventilation, patients had a PaO2:FiO2 while supine of 233 (IQR, 167-265) and compliance of 42 mL per cm H2O (IQR, 34-47).
  • Over these 72 hours, patients underwent prone ventilation for a median of two sessions (range, 1-3), with a median of 18 hours (IQR, 16-22) per session.
  • Twelve patients (38.7%) received concurrent neuromuscular blockade.
  • Median PEEP was 13 cm H2O (IQR, 12-15) while supine at all timepoints and 14 cm H2O (IQR, 12-15) in the prone position.


  • Median patient follow-up was 34 days).
  • Forty-one patients (62.1%) were successfully extubated, among whom the median duration of mechanical ventilation was 16.0 days (IQR, 10.0-21.0).
  • Fourteen patients (21.2%) underwent tracheostomy. Fifty patients (75.8%) were discharged from the ICU. Eleven patients (16.7%) died.


  • 66 patients with COVID-19 respiratory failure 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 (6, 8, 10).
  • Patients exhibited a spectrum of impaired gas exchange and respiratory system mechanics, and very few patients had near normal compliance.
  • Improvements in oxygenation and compliance with prone positioning were consistent with prior studies of prone ventilation in early ARDS.
  • Prone ventilation improves gas exchange in ARDS by increasing aerated areas of lung, among other mechanisms.
  • Patients were managed with established ARDS therapies including low tidal volume ventilation, conservative fluid administration, and, in many cases, prone ventilation.
  • With a minimum follow-up of 30 days, overall mortality was 16.7% and the majority of patients were successfully extubated and discharged from the ICU.

Limitations :

  • The limited duration of patient follow-up in this retrospective study was driven by a focus on respiratory pathophysiology as opposed to clinical outcomes.
  • Some patients were not intubated on the basis of goals and preferences was not included in our cohort.
  • Patients with COVID-19 respiratory failure exhibited similar gas exchange, respiratory system mechanics, and response to prone ventilation as prior large cohorts of patients with ARDS.

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