Awake Prone Position and Endotracheal Intubation in COVID-19 Patients

Quick Takes

  • Although previous studies have demonstrated clinical benefits of prone positioning for intubated patients with ARDS, the benefit for nonintubated patients with COVID-19-related hypoxemia remains unproven.
  • Among 400 nonintubated patients hospitalized with COVID-19-related hypoxemia, randomization to a protocol of prone positioning versus standard care did not produce statistically significant decline in risk of intubation within 30 days, death within 60 days, or other relevant outcomes.
  • A nonstatistical signal toward decreased intubation and ICU admission with prone positioning, plus apparent failure to implement the intervention for an adequate number of hours per day, suggest that further study will be needed to conclusively exclude any possible benefit of prone positioning in this population.

Study Questions:

Among nonintubated patients hospitalized with coronavirus disease 2019 (COVID-19)-related hypoxemia, what is the efficacy of prone positioning to decrease need for intubation, and to decrease incidence of mortality and other adverse clinic events?


In the COVI-PRONE (Awake Prone Position in Hypoxemic Patients With Coronavirus Disease 19) trial, patients with COVID-19 requiring ≥40% supplemental oxygen and/or noninvasive ventilation were randomly assigned to a protocol of daily prone positioning versus standard care without prone positioning at 21 hospitals in Canada, the United States, Saudi Arabia, and Kuwait. The primary outcome was tracheal intubation within 30 days of enrollment. Secondary outcomes included death and intensive care unit (ICU)-free days within 60 days of enrollment, and use of invasive or noninvasive ventilation within 30 days. Daily prone positioning was stipulated until the subject was intubated, had ≥40% improvement in fraction of inspired oxygen (FiO2) requirement for 24 hours, or was discharged from the ICU or acute care unit. Targeted daily duration of prone position was 8-10 hours, and analysis was by intention-to-treat.


A total of 400 patients were enrolled, with 205 randomized to awake prone positioning and 195 to standard care.

Primary outcome:

  • 34.1% in the prone position group versus 40.5% in the control group were intubated within 30 days (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.59-1.12; p = 0.20); absolute risk difference of -6.37% (95% CI -15.83% to 3.10%).
  • Per-protocol analysis showed consistent results, with no statistical difference observed (33.7% vs. 36.3% primary outcome with prone position vs. standard care, HR, 0.89; 95% CI, 0.62-1.28; p = 0.54).

Secondary outcomes at 60 days:

  • Death occurred in 22.4% of patients randomized to prone positioning versus 23.6% patients randomized to standard care (HR, 0.93; 95% CI, 0.62-1.40; p = 0.72); absolute difference, 1.15% (95% CI -9.40% to 7.10%).
  • ICU-free days were 38.6 (23.6) days in the prone position group versus 34.5 (24.6) in the standard treatment group (mean difference, 4.07 days; 95% CI, -0.67 to 8.81 days; p = 0.09).
  • Hospital-free days were 34.4 (22.9) days in the prone position group versus 30.8 (23.5) days in the standard treatment group (mean difference, 3.52 days; 95% CI, -1.05 to 8.08 days; p = 0.13).
  • Adverse events related to prone positioning occurred in 21 patients (10%) randomized to the prone positioning intervention versus 0 patients randomized to standard care. Most events cited positioning-related pain or discomfort, and there were no positioning-related serious adverse events reported.

Secondary outcomes at 30 days:

  • Days free from invasive mechanical ventilation or noninvasive ventilation were 21.4 (12.7) days in the prone position group versus 19.4 (13.2) days in the standard treatment group (mean difference, 2.04 days; 95% CI, -0.50 to 4.59; p = 0.12).
  • Days free from invasive mechanical ventilation were 21.6 (12.4) days in the prone position group versus 19.6 (13.1) days in the standard treatment group (mean difference, 2.03 days; 95% CI, -0.47 to 4.54; p = 0.11).


Use of prone positioning did not statistically reduce the need for intubation within 30 days, nor did it reduce mortality within 60 days or other adverse clinical outcomes among 400 nonintubated patients hospitalized with COVID-19-related hypoxemia.


Previous studies of intubated, sedated patients with acute respiratory distress syndrome (ARDS) have shown statistically significant benefit from prone positioning, but the benefit has been observed only when prone positioning is maintained for longer time periods (12 hours per day). COVI-PRONE subjects randomized to the intervention spent a median of just 4.8 hours prone per day, well below the time stipulated in the study protocol, suggesting that staying prone for an extended time may be difficult for awake patients. Failure to perform the positioning intervention for the intended duration, along with lack of prespecified objective criteria warranting intubation and possibly inadequate sample size, may have led investigators to miss any possible small but clinically important benefits of prone positioning in this population.

Clinical Topics: Prevention

Keywords: Coronavirus, COVID-19, Hypoxia, Brain, Intensive Care Units, Intubation, Intratracheal, Noninvasive Ventilation, Patient Discharge, Primary Prevention, Prone Position, Respiration, Artificial, Respiratory Distress Syndrome, Respiratory Insufficiency, Ventilation

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