1. In this non-randomized controlled trial including 501 patients with COVID-19-associated hypoxemia requiring supplemental oxygen without mechanical ventilation, prone positioning was not found to offer clinical benefits.

2. Prone positioning was found to have an adjusted odds ratio of 1.63 for worse patient outcomes at study day 5 compared to usual care.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Patients with COVID-19 have been shown to develop acute hypoxemic respiratory failure, which in some cases requires invasive mechanical ventilation. A nonpharmacological approach to hypoxemia includes awake prone positioning among patients not receiving mechanical ventilation. This non-randomized controlled trial investigated whether prone positioning was associated with improve clinical outcomes among 501 awake adult patients with COVID-19 hypoxemia requiring supplemental oxygen without mechanical ventilation compared to patients receiving usual care. Patients were assigned to receive either the awake prone positioning intervention or usual care. The primary outcome was the highest level of oxygen support on day 5 according to a WHO COVID-19 ordinal outcome scale. This study found that on day 5, the prone positioning intervention group was more likely to have worse outcomes than usual care (adjusted odds ratio [aOR] = 1.63). Secondary outcomes, such as progression to mechanical ventilation, length of stay and mortality at day 28 did not differ however between groups. The odds of having worsening oxygen requirements among patients receiving the prone position intervention was found to increase from study days 2 through 5. The data from this study suggests that awake prone positioning for patients with COVID-19 associated hypoxemia may worsen clinical outcomes and cause harm. A limitation to this study was that instead of traditional randomization, patients were allocated treatment groups based on medical records. A major strength to this study however that findings of worse outcomes among patients assigned to the intervention group were consistent across multiple post-hoc sensitivity analyses.

Click to read the study in JAMA Internal Medicine

Click to read an accompanying editorial in JAMA Internal Medicine

Relevant Reading: Prone positioning in severe acute respiratory distress syndrome

In-Depth [non-randomized controlled trial]: This study investigated whether awake prone positioning was associated with improved outcomes among patients with COVID-19 related hypoxemia who were not receiving mechanical ventilation. A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] male), were enrolled from 2 academic medical centers between May 13 to December 11, 2020 during the COVID-19 pandemic. 258 patients were assigned to the prone positioning intervention group and 243 patients were assigned to receive usual care. Upon assessing the WHO ordinal scale on each day, it was found that the odds of being in a worse outcome for oxygen delivery among patients receiving the prone position intervention increased from study days 2 through 5.  On study day 5, the intervention group had a posterior probability of 0.998 for having a worse outcome (posterior median aOR, 1.63, 95% high-density credibility intervention [CrI]. 1.16-2.31). On day 14, the posterior median aOR was 1.29 (95% CrI, 0.84-1.99), and the posterior probability of an aOR of 1.0 of greater was 0.874. Finally, on day 28, the aOR for the posterior median was 1.12 (95% CrI, 0.67-1.86) with a probability of an aOR of 1.0 or greater at 0.673. No evidence of a difference in ventilator-free days or the number of patients progressing to mechanical ventilation during the study (31 patients in the intervention group vs. 30 patients in the usual care group) was detected.

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