Early Versus Late Awake Prone Positioning in Non-intubated Patients With COVID-19

Ramandeep Kaur; David L. Vines; Sara Mirza; Ahmad Elshafei; Julie A. Jackson; Lauren J. Harnois; Tyler Weiss; J. Brady Scott; Matthew W. Trump; Idrees Mogri; Flor Cerda; Amnah A. Alolaiwat; Amanda R. Miller; Andrew M. Klein; Trevor W. Oetting; Lindsey Morris; Scott Heckart; Lindsay Capouch; Hangyong He; Jie Li


Crit Care. 2021;25(340) 

In This Article

Abstract and Introduction


Background: Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP.

Methods: Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate.

Results: We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8–12.82) vs 36.35 (30.2–75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0–9.05) and 3.0 (1.09–5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%, p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0–1.95], p = 0.001), intubation (OR 10.65 [95% CI 2.77–40.91], p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0–1.04], p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23–31.1], p = 0.027) were associated with increased mortality.

Conclusions: Early initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival.

Trial registration: ClinicalTrials.gov NCT04325906.


Coronavirus disease (COVID-19) is a viral infectious disease caused by coronavirus (SARS-CoV-2).[1] COVID-19 primarily affects the respiratory system causing mild to severe respiratory illness. Around 25–30% of COVID-19 patients develop signs of acute respiratory distress requiring higher respiratory support in terms of oxygen therapy, noninvasive and invasive positive pressure ventilation.[2] Prone positioning improves oxygenation by the uniform distribution of tidal volume and recruitment of the dorsal lung regions leading to improved lung compliance.[3] Before the COVID-19 pandemic, a small, prospective observational study demonstrated the benefit of using prone positioning among non-intubated patients with moderate acute respiratory distress syndrome (ARDS) to reduce the need for invasive mechanical ventilation.[4] Since the emergence of COVID-19, this technique has been extensively used to improve oxygenation in non-intubated COVID-19 patients with acute hypoxemic respiratory failure (AHRF).[5]

There is evidence demonstrating the benefits of early prone positioning to improve oxygenation and patient outcomes in intubated patients with moderate to severe ARDS.[6] A recent multicenter cohort study investigating the timing of prone positioning initiation among mechanically ventilated patients with COVID-19 found a lower hospital mortality among those who received early prone positioning (within 2 days of ICU admission).[7] Another retrospective, multicenter observational study included 827 non-intubated patients with COVID-19 and found that awake prone positioning (APP) was significantly associated with lower mortality (20.0% vs 37.9%; p < 0.0001) and intubation rate (23.6% vs 40.4%; p < 0.0001) as compared to supine position.[8] Randomized controlled trials have been done to evaluate the feasibility of implementation and patient compliance with APP in patients with COVID-19, but no long-term outcomes were assessed.[9–13] A recent systematic review found that APP improved oxygenation among patients with AHRF due to COVID-19, however, APP did not reduce intubation rates.[14] Finally, a collaborative meta-trial of six randomized controlled superiority trials, on which this post hoc analysis is based, enrolled a total of 1121 patients and found hazard ratios of 0.75 (95% CI, 0.62–0.91) for intubation and 0.87 (95% CI, 0.68–1.11) for 28-day mortality with APP, as compared to the standard care group.[15]

Despite multiple studies showing benefit of prone positioning among non-intubated patients with COVID-19, there is no clear evidence available guiding the timing of awake prone positioning for patients with COVID-19 to achieve optimal patient outcomes.[16] Therefore, the primary objective of this study was to compare early versus late initiation of awake prone positioning (APP) on patient outcomes, including hospital mortality and the need for invasive mechanical ventilation (IMV).