The clinical impact of early spontaneous breathing during veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome (ARDS) is unclear, balancing potential benefits (reducing sedation and preserving diaphragm function) against risks of patient self-inflicted lung injury (P-SILI).

Explore whether early transition to sustained spontaneous breathing (≤5 days after ECMO initiation) may be associated with improved ICU outcomes.

Multicenter cohort study across eight Dutch ECMO centers, including adult ARDS patients on mechanical ventilation supported with VV ECMO. Sustained spontaneous breathing was defined as the first episode of spontaneous breathing sustained across two consecutive days. ICU mortality was analyzed using multistate and landmark Cox models; liberation from ventilation, ECMO, and ICU discharge by day 60 were assessed with competing risk regression, adjusted for Respiratory ECMO Survival Prediction (RESP) score.

Among 123 patients, median time to sustained spontaneous breathing was 5.0 days (IQR 1–12). Across landmark times from ECMO day 1 through 14, transitioning on any given days was not associated with a difference in ICU mortality. After RESP adjustment, early sustained spontaneous breathing was associated with higher rates of extubation and ICU discharge by day 60.

Early spontaneous breathing was associated with higher adjusted rates of extubation and ICU discharge in an exploratory analysis; however, these findings should be interpreted cautiously because of residual confounding, selection bias, and immortal-time bias. This study highlights the need for randomized trials incorporating physiological markers of safe transition to help identify patients that could benefit.