Can early ECMO improve outcomes for severe ARDS?


‘Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome’ Combes et al. N Engl J Med 2018; 378:1965-1975


  • ARDS (acute respiratory distress syndrome) is associated with high mortality
  • Oxygenation and carbon dioxide removal can be performed by VV-ECMO (veno-venous extracorporeal membrane oxygenation), however it is associated with significant complications. A previous RCT (CESAR trial – Conventional VentilatorySupport versus Extracorporeal MembraneOxygenation for Severe Adult Respiratory Failure), yielded promising results, however came under criticism for methodological issues and limited conclusions could be drawn. 
  • The question of whether ECMO improves outcomes in ARDS compared to standard lung-protective ventilation remains unanswered. 

Aim:The ECMO to rescue lung injury in severe ARDS (EOLIA) trial was designed to determine the effect of early initiation of ECMO in patients with the most severe form of ARDS. 


  • Prospective, randomised controlled trial, 64 centres, mainly France
  • Patient selection
    • Ventilated for < 7 days
    • American-European ARDS definition, 1994
  • Randomization was stratified according to center and the duration of ventilation before randomization (<72 hours vs ≥72 hours)
  • Target sample size was 331 patients
    • Based an expected 60 day mortality rate of 60%, and an estimated 40% mortality in the ECMO group (absolute risk reduction 20%)
    • For 80% power at an alpha level of 5% and with a group­ sequential analysis occurring after the randomization of every 60 participants
  • Stopping rules, using the two sided triangular design methodology, were defined prior to the commencement of the trial. The trial could be stopped due to:
    • Safety (due to excess mortality in the ECMO arm)
    • Efficacy
    • Futility 


  • Venovenous ECMO
    • Percutaneous cannulas, with the access cannula inserted into the femoral vein and return cannula inserted into the SVC via the jugular vein


Volume-assist-controlled ventilation

  • FIO2 (0.21–1) was adjusted to obtain sats between 88-95% and a PaO2 55-80 mmHg
  • VT set at 6 ml per kg PBW
  • PEEP set so as not to exceed a Pplat of 28–30 cmH2
  • NMBAs and prone positioning encouraged for control patients


  • Trial was stopped early at 249/331 (75% of recruitment) due to predefined futility rules.
  • Primary outcome: No statistical difference in mortality at day 60
    • ECMO group 44/124 (35%) vs Control group 57/125 (46%)
    • Relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09
  • Secondary outcomes:
    • Compared to control group, the ECMO group had:
      • Lower relative risk of treatment failure 0.62 (95% CI, 0.47 to 0.82; P<0.001)
        • Treatment failure was defined as death by day 60 in patients in the ECMO group, and as crossover to ECMO or death in patients in the control group
      • Lower risk of Renal replacement therapy (RRT) at day 60 (50 vs. 32 days; median difference, 18 days; 95% CI, 0 to 51)
    • Cross over to ECMO occurred in 35/125 (28%) of control patients



  • Largest multicenter ECMO RCT to date
  • Standardised criteria for entry into the trial/ initiation of rescue ECMO
  • Almost all patients who were randomized to ECMO received it (unlike the previous RCT, CESAR)
  • Protocolized delivery of ECMO and MV àhence standardised treatments in intervention and control arms (patients were included from both ECMO and non-ECMO centres on the proviso ECMO could be initiated with 2 hours of randomisation).


  • Underpowered to detect mortality -> trial stopped early! (75% recruitment)
  • Implausible power calculation (mortality in the control group was 46%, not 60%)
  • High cross over rate of controls
  • Lack of blinding 
  • Slow recruitment of 249 patients over 6 years à trial fatigue and/or change of practice


ECMO for severe ARDS showed no significant mortality benefit at day 60 as compared with a strategy of conventional mechanical ventilation.

Summary by Dr Clare Morkane

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