Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Associated with COVID-19: An Emulated Target Trial Analysis

RATIONALE: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-day mortality versus IMV only. METHODS: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (Pa(O(2))/Fi(O(2)) < 80 or Pa(CO(2)) ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. MEASUREMENTS AND MAIN RESULTS: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0–9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, −2%; 95% confidence interval, −10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. CONCLUSIONS: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.