Combes A, Hajage D, Capellier G et al. for the EOLIA Trial Group, REVA, and ECMONet*
Clinical Question
In patients with severe ARDS, does the early initiation of Extracorporeal Membrane Oxygenation (ECMO), compared to standard care, improve mortality at day 60?
Study Design
- Prospective, multicenter, randomized controlled trial
- Research staff members responsible for the primary outcome were blinded, while participants, medical and nursing staff were not blinded
- Patients were randomly assigned to EITHER receive immediate venovenous ecmo (ECMO GROUP) OR continue on conventional treatment (CONTROL GROUP).
- Crossover to ECMO was possible for patients in control group who had refractory hypoxaemia.
- Primary end point – mortality at 60 days.
- Stopping rules, (using the two sided triangular methodology)were defined prior to the commencement of the trial. Trial could be stopped due to:
- Safety due to excess mortality in ECMO group
- Futility (unlikely to reach a definitive result)
Inclusion Criteria
- ARDS (American-European Consensus Conference definition, 1994)
- Endotracheal intubation of <7 days,
- one of the following disease-severity criteria despite optimisation of mechanical ventilation (FIO2>80%, tidal volume 6 ml per kg, predicted body weight and PEEP>10 cm of water) and despite potential use of various usual adjunctive therapies (inhaled nitric oxide, recruitment manoeuvres, prone position, high frequency oscillation (HFO) ventilation, almitrine infusion):
- PaO2:FIO2 ratio <50 mmHg for >3 hours; or,
- PaO2:FIO2 <80 mmHg for >6 hours; or,
Arterial blood pH <7.25 with a partial pressure of arterial carbon dioxide (PaCO2) >60 mmHg for >6 hours
Exclusion Criteria
<18 years old, MV >7 days, Pregnancy, Overweight , Long-term chronic respiratory insufficiency treated with oxygen therapy or noninvasive ventilation, Cardiac failure resulting in venoarterial ECMO, A history of heparin-induced thrombocytopenia, Cancer with a life expectancy of less than 5 years, A moribund condition or a Simplified Acute Physiology Score (SAPSII) value of more than 90, A current non–drug induced coma after cardiac arrest, Irreversible neurologic injury, A decision to withhold or withdraw lifesustaining therapies
Outcome
- Primary outcome: No statistical difference in mortality at day 60 ECMO group 44/124 (35%) vs Control group 57/125 (46%)
- 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)
- Underwent less proning (59 vs. 46 days; median difference, 13 days; 95% CI, 5 to 59)
- Lower relative risk of treatment failure 0.62 (95% CI, 0.47 to 0.82; P<0.001)
Strengths
- Important and relevant research question about the effectiveness of ECMO in severe ARDS
- Largest multicenter ECMO RCT to date
- Standardised criteria for entry into the trial, and for the initiation of rescue ECMO
- Protocolized delivery of ECMO and MV resulted in standardized treatments in both intervention and control arms
Weaknesses
- Underpowered to answer the trial question
- High cross over rate of controls
- lack of blinding of clinicians and patients/families (however difficult in such a trial)
- Threats to external validity
- Expertise of ECMO centers not clearly defined
- Importance of VV ECMO configuration is uncertain (i.e. femoral-jugular versus femoral-femoral approach)
Summary by Dr A Thillainathan. Journal Club Meeting 10 January 2019.
