Standard Care Versus Awake Prone Position in Adult Nonintubated Patients With Acute Hypoxemic Respiratory Failure Secondary to COVID-19 Infection—A Multicenter Feasibility Randomized Controlled Trial

Abstract

Rationale: The feasibility and safety of awake prone positioning and its impact on outcomes in non-intubated patients with acute respiratory distress syndrome secondary to COVID-19 is unknown. Results of the observational studies published during this pandemic have been conflicting. In this context, we conducted a multi-center, parallel group, randomized controlled feasibility study on awake prone positioning in non-intubated patients with COVID-19 pneumonia requiring supplemental oxygen. Methods: 60 patients with acute hypoxic respiratory failure secondary to COVID-19 pneumonia requiring 4 or more liters of oxygen to maintain a saturation of ≥92% were recruited in this study. Thirty patients each were randomized to either standard care or awake prone group. Patients randomized to the prone group were encouraged to self-prone for at least 6 hours a day. The primary outcome was the proportion of patients adhering to the protocol in each group. Results: In the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. In the supine group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 hours. There was no significant difference in any of the secondary outcomes between the 2 groups and there were no adverse events. Conclusions: Awake prone positioning in non-intubated patients with acute hypoxic respiratory failure is feasible and safe under clinical trial conditions. The results of our feasibility study will potentially help in the design of larger definitive trials to address this key knowledge gap.

Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis

“…The primary outcome was the cumulative intubation risk across RCTs; the measure of effect was risk ratio (RR; 95% CI). Secondary outcomes included the reported all-cause mortality; the need for escalating respiratory support, which was defined as progression to a higher level of oxygen or respiratory support (room air<conventional oxygen therapy<high-flow nasal cannula<non-invasive ventilation [NIV]<invasive ventilation) according to the included studies; 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 the duration of ICU and hospital stay; and safety outcomes, including cardiac arrest, vomiting, and central or arterial line dislodgement. We also performed a post-hoc analysis on ICU admission among patients who were not admitted to the ICU at enrolment and added it as a secondary outcome.…”

“…10 In August, 2021, an international randomised controlled meta-trial with more than 1100 patients found that awake prone positioning significantly reduced intubation need and treatment failure for patients with COVID-19-related acute hypoxaemic respiratory failure requiring support with high-flow nasal cannula. 11 However, before this publication, six randomised controlled trials (RCTs) with a smaller sample size than the meta-trial, 12 , 13 , 14 , 15 , 16 , 17 and two completed but unpublished multi-centre RCTs that enrolled 248 patients 18 and 293 patients, 19 respectively, did not find that awake prone positioning reduced the intubation need for patients with COVID-19; and, three RCTs 12 , 13 , 18 found that patients' adherence to awake prone positioning was low. In the two most recent meta-analyses that included RCTs, 20 , 21 Fazzini and colleagues included two RCTs 11 , 14 and 12 observational studies, and they reported uncertainty regarding the effects of awake prone positioning on intubation and survival, 20 whereas Beran and colleagues included five RCTs 11 , 12 , 13 , 14 , 16 and nine observational studies, and they reported that awake prone positioning has a benefit on mortality.…”

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial

“… 9 , 10 , 11 Two small (n=30 and n=60) pilot trials studied the feasibility of awake prone positioning in non-intubated patients but did not have the power to show improvement in oxygenation, escalation of respiratory support, or mortality. 12 , 13 Despite the paucity of large scale randomised controlled evidence evaluating patient-centred outcomes, awake prone positioning generated great interest in the clinical and scientific communities, and it has been incorporated into clinical guidelines 14 and expert consensus statements. 15 , 16 Awake prone positioning has been identified as a research priority by the Surviving Sepsis Research Committee.…”

Management of COVID-19-Associated Acute Respiratory Failure with Alternatives to Invasive Mechanical Ventilation: High-Flow Oxygen, Continuous Positive Airway Pressure, and Noninvasive Ventilation

“…An RCT feasibility study of 60 patients with hypoxic ARF secondary to COVID-19 pneumonia found no effect of prone position on the need for additional respiratory therapy or mortality; however, only 13 patients encouraged to lay in the prone position were able to self-prone for at least 6 h a day. In the standard care group, 16 patients chose by themselves to spend time in the prone position, which may have masked an effect [ 86 ]. A pilot trial designed as a cluster study in a quaternary care center included five inpatient medical service teams to either encourage prone positioning or standard care with no randomization of patients found no effect on oxygen saturation to fraction of inspired oxygen ratio of encouragement of medical service teams to prone positioning [ 87 ].…”