REBEL Cast Ep110: The COVI-PRONE Trial – Awake Prone Positioning and COVID-19

Background: Early in the COVID-19 pandemic, clinicians were looking for practical, widely available, and low-cost interventions to help patients with hypoxemia.  One of those interventions was awake prone positioning.  Potential mechanisms of benefit in awake proning include more uniform distribution of tidal volume, recruitment of areas in the posterior part of the lung, improved ventilation/perfusion, and improved lung compliance, just to name a few. A systematic review and meta-analysis of 2 RCTs and 12 observational trials (Link is HERE) found no statistically significant association of awake prone positioning with the risk of endotracheal intubation.  However, our conclusion was an absence of evidence, is not an absence of benefit. Another meta-trial looking at 6 RCTs (Link is HERE) found a 3% non-statistically significant difference in intubation and an 11% non-statistically significant difference in mortality.  Both of these numbers could represent important differences, but larger studies are needed to flesh this out.

REBEL Cast Ep110: The COVI-PRONE Trial – Awake Prone Positioning and COVID-19

Paper: Alhazzani W et al. Effect of Awake Prone Positioning on Endotracheal Intubation in Patients with COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2022. PMID: 35569448 [Access on Read by QxMD]

 Clinical Question: Does prone positioning reduce endotracheal intubation in adults who are not intubated with hypoxemic respiratory failure from COVID-19?

What They Did:

• Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19 (COVI-PRONE)
• Pragmatic, unblinded randomized clinical trial
• Conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US
• Patients randomized to:
  • Awake prone positioning
    • Targeted for 8 to 10hrs/d with 2 to 3 breaks (1 to 2hrs each) if needed
  • Usual care without prone positioning

Outcomes:

• Primary: Endotracheal intubation within 30d of randomization
• Secondary:
  • Mortality at 60d
  • Days free from invasive mechanical ventilation or noninvasive ventilation at 30d
  • Days free from ICU or hospital at 60d
  • Adverse events
  • Serious adverse events

Inclusion:

• Adult patients (≥18 years of age) with COVID-19
• Not intubated
• Suspected or confirmed COVID-19
• Requiring oxygen (≥40%) or noninvasive ventilation
• Being treated in ICU or acute care unit

Exclusion:

• On invasive mechanical ventilation
• Contraindications to prone positioning
• Risk of complications from prone positioning
• Self-prone positioning prior to enrollment

Results:

• 400 patients enrolled
  • 97% of patients had confirmed COVID-19
  • Median SpO2/FiO2:
    • Awake Prone Position: 132 (Range: 103 to 174)
    • Usual Care: 136 (Range 110 to 181)
  • 60% of patients enrolled had an SpO2/FiO2 ≤150
  • 95% of patients received corticosteroids
  • 78% of patients received prophylactic dose anticoagulants
• Median duration of prone positioning
  • Awake Prone Position: 4.8hr/d (Range 1.8 to 8.0hr/d)
  • Usual Care: 0hr/d (Range 0 to 0hr/d)
• Need for Intubation at 30d:
  • Awake Prone Position: 34.1%
  • Usual Care: 40.5%
  • Difference: -6.37%; 95% CI -15.83% to 3.10%
• Mortality at 60d:
  • Awake Prone Position: 22%
  • Usual Care: 24%
  • HR: 0.89; 95% CI 0.62 to 1.28; p = 0.72
• Prone positioning did not have a statistically significant effect on days free from ICU or NIV at 30d
• No serious adverse events in either group
• Adverse Events:
  • Awake Prone Position: 10%
    • Musculoskeletal pain/discomfort from prone position 13/205pts (6.34%)
    • Desaturation 2/205pts (0.98%)
  • Usual Care: 0%

Strengths:

• Asks a clinically important question
• Randomized, multicenter trial
• 100% of patients enrolled completed the trial
• Groups were equally balanced in baseline characteristics

Limitations:

• Missed 195 eligible patients. With 400 patients randomized, this would be the equivalent of half the enrolled population.  It is unclear what effect this would have on the results
• Only 400 patients enrolled across 21 institutions over a year suggests a significant selection bias
• Proning for only 4 to 5hrs/day
• Decision to intubate is a subjective one. In a non-blinded study, this could impact what was done in each group
• In the control group 20% of patients underwent prone positioning after randomization which would dilute the difference between the two groups which would bias the results to a negative outcome for prone positioning

Discussion:

• An important point to remember is that early in the COVID-19 pandemic there was a shift in the threshold for endotracheal intubation. Many stopped simply intubating hypoxemic patients, and attempted trials of non-invasive oxygenation while also tolerating slighting lower oxygen saturations.
• This study showed a 6% decrease in intubation rates. That’s pretty impressive, but the study simply isn’t powered to see that as significant even though we would find it to be.
• A preplanned subgroup analysis showed a possible reduction in endotracheal intubation risk with prone positioning in patients with SpO2:FiO2 >150 and in those receiving high-flow oxygen. It is possible that patients with more severe disease do not benefit from awake proning
• This study was most likely too small and not powered correctly. A 6% reduction in intubation, although not statistically significant is clinically meaningful. There was another larger meta-trial  of 6 RCTs (Link is HERE) that totaled 1100 patients that showed a 6% reduction to be statistically significant

Author Conclusion: “In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days.  However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.”

Clinical Take Home Point:  Despite the authors conclusion of no benefit from awake prone positioning, a 6% reduction in intubation (non-statistically significant) is clinically meaningful. This means either looking for a 13.5% reduction in the primary outcome was too big or the study was simply too small and inadequately powered.  In the context of all the trials available, a 6% difference in intubation is clinically important and consistent across studies. In our opinion there is still a role for awake prone positioning.

References:

1. Alhazzani W et al. Effect of Awake Prone Positioning on Endotracheal Intubation in Patients with COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2022. PMID: 35569448 [Access on Read by QxMD] 

For More Thoughts on This Topic Checkout:

• REBEL EM: COVID-19 – Awake Proning
• REBEL EM: Awake Proning for COVID-19 Acute Hypoxemic Respiratory Failure
• REBEL EM: COVID-19 Awake Proning – All Hype?

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

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