The role of extracorporeal membrane oxygenation (ECMO) in the management of acute respiratory distress syndrome (ARDS) has been a source of debate within the critical care community.¹ The use of ECMO has steadily increased over the past decade;² however, evidence to support the widespread adoption of this expensive and invasive technology is limited. As advances in ECMO technology have rapidly outpaced evidence, clinicians have been left to speculate as to ECMO’s true value. Is ECMO a promising tool to advance the care of patients with respiratory failure³ or an expensive distraction that has inappropriately supplanted evidence-based strategies?⁴

All who care for patients with ARDS have been eagerly awaiting the results of the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial which were recently published in May 2018’s New England Journal of Medicine.⁵

Clinical Question

Does the early use of ECMO improve mortality in adult patients with severe ARDS?

Methods

The EOLIA trial was an international randomized controlled trial conducted primarily in France. The trial enrolled adults with early severe ARDS. To be eligible, patients had to meet at least 1 of the following criteria within 7 days of the initiation of mechanical ventilation:

1. PaO/FO < 50 mmHg for > 3 hours
2. PaO/FO < 80 mmHg for > 6 hours
3. pH < 7.25 + PaCO ≥ 60 mmHg for > 6 hours

Patients were randomized to ECMO or a control arm, which followed evidence-based practices for ARDS including all of the following:

1. Lung-protective ventilation (e.g., low tidal volumes and low plateau pressures)
2. Neuromuscular blockade
3. Prone positioning

Crossover from the control arm to the ECMO arm was allowed for 6 hours of refractory hypoxemia. The trial was designed to detect a 20% mortality reduction in patients randomized to ECMO.

Results

1,015 patients were screened and 249 underwent randomization. Pneumonia was the most common etiology of ARDS (64%). The median time from intubation to randomization in both groups was 34 hours. Overall, patients were quite ill with the mean PaO/FObeing roughly 70 mmHg (“severe ARDS” is defined as PaO/FO < 100 mmHg) and 70% were on vasopressors. All but 3 patients in the ECMO arm were placed on ECMO.

Patients in both groups were receiving evidence-based ARDS management at the time of randomization:

1. The mean tidal volume in both arms was 6 mL/kg of predicted body weight (PBW).
2. The mean plateau pressure was < 30 cmHO.
3. Over 90% of patients were on neuromuscular blockade.
4. Over 50% received prone positioning.

The trial was stopped for futility after the 4th planned interim analysis by an independent data safety monitoring board according to pre-specified criteria. In an intention-to-treat analysis, 60-day mortality was 35% in the ECMO group vs 46% in the control arm (relative risk 0.76; 95% CI, 0.55-1.04, p=0.09). Because there was an an extremely low probability of finding a benefit to ECMO at subsequent analyses, the trial was stopped.

Of note, 28% of patients in the control arm received rescue ECMO for refractory hypoxemia. These patients had a 60-day mortality of 57%.

Conclusion

In patients with severe ARDS, the early use of ECMO did not significantly improve 60-day mortality compared to standard care.

Take-Home Points for Emergency Physicians

Does this end the debate about ECMO in ARDS?

Unfortunately, no. ECMO skeptics will see EOLIA as further evidence that routine ECMO use should be abandoned; proponents will point to the 11% difference in 60-day mortality between the 2 arms at the time the trial was stopped and the signal of benefit in a secondary composite end point as evidence that ECMO does indeed have a role in the management of severe ARDS. Our ability to now manage select patients on ECMO without mechanical ventilation (so that a patient with ARDS can now be extubated, awake, eating, and working with physical therapy while on ECMO) ensures this will be an area of controversy and innovation for the foreseeable future.⁶

How is this relevant for the Emergency Department?

ARDS is not exclusively an Intensive Care Unit (ICU) diagnosis; EM providers care for patients with ARDS^7,8 and should be familiar with evidence-based management strategies. The publication of EOLIA provides a timely opportunity to review some key aspects of ARDS management for EM providers:

• The delivery of cutting-edge ARDS care depends on prompt recognition. Emergency physicians should know the Berlin Definition of ARDS⁹ and review the diagnosis criteria for every patient intubated for hypoxemic respiratory failure. If your patient has a PaO2/FiO2 ≤ 300 mmHg and bilateral opacities on imaging that you don’t think is primarily due to heart failure or volume overload, think ARDS.
• Sepsis and pneumonia are the most common risk factors for ARDS.¹⁰
• The cornerstone of ARDS management remains mechanical ventilation with low tidal volumes (a goal of 6 mL/kg PBW) and low plateau pressures (< 30 cmHO). Despite widespread consensus that this strategy saves lives, it is implemented with distressingly low frequency in both the Emergency Department⁷ and the ICU.¹⁰
• The control arm of EOLIA provides a nice snapshot of high-level ARDS care. Almost all patients received mechanical ventilation with low tidal volumes and low plateau pressures in addition to early neuromuscular blockade and prone positioning. A conservative fluid management strategy would be the other important evidence-based component of early ARDS care¹¹ that is not explicitly mentioned in the trial. The adoption of prone positioning has been one of the biggest advances in the care of ARDS patients since the publication of a landmark trial in 2013.¹²
• The availability of advanced therapies for ARDS including ECMO and prone positioning varies highly by center. EM providers should know what options are available at their institution and be familiar with any institutional protocols to guide their use. As an example, at my institution there is a multidisciplinary ECMO team that can be rapidly mobilized to discuss management options for patients in the Emergency Department with refractory hypoxemia.

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