Extracorporeal Carbon Dioxide Removal in Acute Respiratory Distress Syndrome: Physiologic Rationale and Phenotype-Based Perspectives

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality despite decades of progress in ventilatory support. Mechanical ventilation, while essential for oxygenation, may exacerbate lung injury through excessive mechanical power delivery, even when using lung-protective strategies. Extracorporeal carbon dioxide removal (ECCO₂R) was conceived to enable "ultra-protective" ventilation, allowing for further reductions in tidal volume and respiratory rate by selectively removing CO₂ at low extracorporeal blood flows, typically between 0.3 and 1.0 L/min. This physiological decoupling of ventilation and gas exchange aims to mitigate ventilator-induced lung injury (VILI) while maintaining adequate acid-base homeostasis. Although early physiological studies demonstrated feasibility, large, randomized trials have failed to show a survival benefit and have raised concerns about bleeding and technical complications. Recent evidence suggests that these neutral outcomes may stem from the biological and physiological heterogeneity of ARDS rather than from inefficacy of the intervention itself. Patients with high driving pressures, poor compliance, or hyperinflammatory phenotypes may derive greater benefit from ECCO₂R-mediated mechanical unloading. Ongoing technological improvements, including circuit miniaturization, enhanced biocompatibility, and integration with renal replacement therapy, have improved safety and feasibility, yet the procedure remains complex and resource-intensive. Future research should focus on phenotype-enriched trials and the integration of ECCO₂R into precision ventilation frameworks. Ultimately, ECCO₂R should be regarded not as a universal therapy for ARDS but as a targeted physiological tool for selected patients in experienced centers.