Prone Positioning in Non-Intubated Patients With COVID-19 Outside of the Intensive Care Unit: More Evidence Needed

The coronavirus disease (COVID-19) pandemic has brought the Italian National Health System to its knees. The abnormally high influx of patients, together with the limited resources available, has forced clinicians to make unprecedented decisions and provide compassionate treatments for which little or no evidence is yet available. This is the case for the use of noninvasive positive pressure ventilation and continuous airway pressure ventilation, combined with prone position in patients with COVID-19 and acute respiratory distress syndrome treated outside of intensive care units. In our article, we comment on the evidence available, so far, and provide a brief summary of data collected at our health institution in Piedmont, Italy.

I taly is a high-income country; however, the ongoing coronavirus disease (COVID-19) pandemic turned hospitals into low-resource battlefields where the provision of the best level of care for a single patient was no longer feasible and "the best for the most" was the only possible alternative. Even though health facilities have made an unprecedented effort to expand their surge capacity, intensive care units (ICUs) have been under strain with health professionals struggling to provide appropriate care to wave after wave of critically ill patients.
Prone positioning (PP) improves oxygenation and decreases mortality in intubated patients with acute respiratory distress syndrome (ARDS). Even if, theoretically, the same benefits should apply to awake patients, the use of PP in non-intubated patients has seldom been described before the COVID-19 outbreak. [1][2][3][4] Interestingly, as the pandemic continues its spread across the globe, the shortage of ventilators and ICU beds is driving clinicians to increasingly use PP outside of ICUs in an attempt to avoid or delay endotracheal intubation. 5,6 Sartini et al. 5 have recently published a small case series of COVID-19-positive patients with mild-to-moderate ARDS treated with noninvasive ventilation (NIV) and PP, reporting that respiratory parameters improved after pronation. Similarly, Elharrar et al. 6 published a prospective study with 24 patients requiring oxygen supplementation where PP was well tolerated, but had a limited effect on oxygenation. Albeit highly relevant, both investigations presented an important limitation: the follow-up period in both studies was limited to 14 and 10 days, respectively. Therefore, intubation rate and outcomes could not be provided for all patients.
We hereby present data from a retrospective case series of 13 COVID-19-positive patients with moderateto-severe ARDS treated at Nuovo Ospedale degli Infermi di Biella, a 500-bed suburban hospital in Piedmont, one of the most severely hit Italian regions. Patients received helmet continuous positive airway pressure (CPAP) with 0.6 fraction of inspired oxygen (FiO2) and 10 CMH20 positive end-expiratory pressure (PEEP) and were pronated in general wards if PaO2:FiO2 < 150 mmHg. Endotracheal intubation was performed in case of respiratory failure, hemodynamic instability, or multiorgan failure. PP was maintained as long as it was well tolerated. The Wilcoxon test was used to compare PaO2:FiO2 and the respiratory rate before and after PP. Analyses were performed using Stata 15 Software (Stata Corp, College Station, TX). A P-value less than 0.05 was considered statistically significant.
Demographic data, coexisting chronic diseases, respiratory parameters before and after PP, laboratory values, and patient outcomes are reported in Table 1. Mean  Prone Positioning in Awake COVID-19 Patients (SD) age was 66.3 years (7.7 years). Mean (SD) PaO2:FiO2 before PP was 115 (13). Our results showed an improved PaO2:FiO2 compared to baseline in 12 patients (P = 0.003).
No difference was found in the respiratory rate before and after PP (P = 0.20). Only 4 patients (30%) avoided intubation and 6 (46%) survived and were discharged home. Interestingly, the improvement in PaO2:FiO2 appeared to be greater in survivors but didn't achieve significance (P = 0.668).
To our knowledge, this is the first study on CPAP with PP in COVID-19 patients. The oxygenation results are consistent with those of Sartini et al. 5  Finally, our results do not suggest a lower intubation or death rate. However, no conclusions can be drawn at the current stage given the retrospective study design, small sample size, lack of control group, and incomplete data of our case series and other published studies.
Importantly, pending results from ongoing randomized controlled trials (NCT04347941, NCT04350723), the outcomes of all COVID-19 patients with ARDS included in small case series and treated with NIV combined with PP would supply more helpful information on whether an improvement in PaO2:FiO2 could translate into avoidance of intubation and increased survival.