Studies in patients with acute respiratory distress syndrome (ARDS) have shown that mechanical ventilation strategies that incorporate lower tidal volumes (Vts) reduce ventilator-induced lung injury (VILI) and improve patient outcomes (1). Current guidelines strongly recommend protective mechanical ventilation strategies that target lower Vt (4-8 mL/kg predicted body weight [PBW]) and lower inspiratory pressures (plateau pressure [< 30 cm H 2 O]) (2). More substantial reductions in Vt (≤ 3 mL/kg PBW), termed "ultraprotective lung ventilation, " may provide further benefit (3). However, such ventilation strategies often result in severe respiratory acidosis (1), which may be associated with adverse outcomes including acute right ventricular dysfunction. Therefore, removing Co 2 extracorporeally to optimize blood pH with the use of an extracorporeal Co 2 removal (ECCO 2 R) device may facilitate ultraprotective ventilation strategies and mitigate VILI (4).Although venovenous extracorporeal membrane oxygenation (ECMO) enables ultraprotective ventilation strategies and provides near-total gas exchange support in selected patients with severe ARDS who fail conventional lung-protective ventilation strategies, low-flow ECCO 2 R is a related technology that provides Co 2 removal at much lower operational blood flows (typically < 1.5 L/min) (4). Unlike ECMO, this blood flow is insufficient to maintain oxygenation (5) in severe ARDS, and thus low-flow ECCO 2 R device use may be limited to mild-moderate ARDS (6). ECCO 2 R, however, is invasive, costly, and carries significant risks including hemorrhage, hemolysis, and thrombosis despite smaller cannulae and specifically marketed low-flow devices. Applying ECCO 2 R to reduce Vt to very low levels may also worsen lung mechanics by increasing atelectasis and hypoxemia (7). To optimize the balance of benefit and risk, ECCO 2 R should ideally be applied specifically to patients who stand to accrue the greatest clinical benefit (8, 9).The protective ventilation with venovenous lung assist in respiratory failure (REST) trial (10) evaluated the use of a low-flow, venovenous ECCO 2 R device (Hemolung; A-Lung Technologies, Pittsburgh, PA; maximal blood flow rate of up to 550 mL/min and Co 2 removal capacity of approximately 80-90 mL/min) to facilitate ultraprotective ventilation (Vt ≤ 3 mL/kg PBW) in patients with acute hypoxemic respiratory failure (AHRF), whereas the comparator group received standard lung-protective ventilation. Of note, this study comprised a heterogenous cohort, with just 53% in the intervention, and 55% in the conventional arm satisfying a diagnosis of ARDS at inclusion. The trial was discontinued by the data monitoring and ethics committee prior to the recruitment *See also p. 892.