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

<b>Rationale:</b> Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. <b>Objectives:</b> To estimate the effect of ECMO on 90-day mortality versus IMV only. <b>Methods:</b> 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_O₂/Fi_O₂ < 80 or Pa_CO₂ ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. <b>Measurements and Main Results:</b> 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. <b>Conclusions:</b> 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.