COMMENTARY

Prone Positioning Before ECMO Is 'Underutilized'

Aaron B. Holley, MD

Disclosures

August 23, 2018

The authors of a recent perspective in the American Journal of Respiratory and Critical Care Medicine (AJRCCM)[1] argued that proning before venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory distress syndrome (ARDS) is underused; their research found that proning occurs in only about 31% of patients. They based their conclusions on data from published reports, as opposed to well-controlled studies, so inferences were limited.

The recently published EOLIA trial[2] allows us to assess proning and VV-ECMO rates in a prospectively enrolled, well-standardized population. Whereas much has been written about sample size and early termination[3] and the primary outcome,[4] there has been less commentary on proning rates.

EOLIA was an international trial that enrolled patients with very severe ARDS and randomly assigned them to VV-ECMO versus conventional treatment. There was no difference between groups in the primary outcome: mortality at 60 days. But the trial was stopped early, and 35 (28%) patients in the control group required "rescue ECMO." The following secondary outcomes were significantly improved in the VV-ECMO group at 60 days: relative risk for treatment failure and days without prone positioning, renal replacement therapy, renal failure, and cardiac failure.

At the time of randomization, after a median of 34 hours of mechanical ventilation in both arms and 3-6 hours of severe ARDS (inclusion criteria available in the study appendix), a total of 148 (59.4%) patients were proned-even though "prolonged periods of prone positioning were strongly encouraged" by the trial investigators. Of note, almost as many patients (132 [53.0%]) had received a pulmonary vasodilator (inhaled nitric oxide or prostacyclin) at randomization. By day 60, 113 (90%) of the patients in the control group had been proned.[2] Unfortunately, we cannot say with certainty whether proning occurred before or after rescue VV-ECMO in the control group.

So, proning rates before VV-ECMO were significantly higher than those reported by the AJRCCM perspective. That is good news, even if it comes within the context of a clinical trial. That said, one could argue that the rates of proning should have been higher. PROSEVA[5] reported a significant reduction in mortality from proning patients with ARDS. Patients in EOLIA would have met the enrollment criteria for PROSEVA, so why weren't they all proned at enrollment? Furthermore, it is disappointing that proning rates were similar to expensive vasodilator therapies (eg, nitric oxide) with no mortality benefit that are not recommended by guidelines.[6,7]

Can EOLIA tell us whether all patients should be proned before VV-ECMO? No. One could say that EOLIA compared early VV-ECMO versus proning (in 90% of patients) with rescue VV-ECMO, but proning delays in the control group limit conclusions. A comparison of treatment group patients who were not proned with control patients who were might be helpful, but this was not provided. Even if it were, it is unlikely there would be a difference, given that the analysis requires cutting the sample size in half.

In the end, I believe EOLIA confirms that proning is underutilized. Barring resource limitations, I agree with the conclusions from the AJRCCM perspective. As a general rule, all patients with ARDS should be proned before starting VV-ECMO.

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