Rationale: In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas V˙V˙e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO₂ removal (ECCO₂R), provided oxygenation remains acceptable.

Objectives: To compare the effects of ECCO₂R and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury.

Methods: Twenty-four pigs with moderate to severe hypoxemia (Pa_O2:Fi_O2 ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50–60 ml/kg/min), ECCO₂R (0.4 L/min), or mechanical ventilation alone.

Measurements and Main Results: V˙V˙o₂, V˙V˙co₂, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; P < 0.001), worse oxygenation (Pa_O2:Fi_O2 = 125 ± 14 vs. 151 ± 11 mm Hg; P < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm H₂O; P = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCO₂R (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; P = 0.003). V˙V˙o₂ and V˙V˙co₂, irrespective of lung injury model, were lower during ECMO, resulting in lower Pa_CO2 and V˙V˙e but worse respiratory elastance compared with ECCO₂R (64 ± 27 vs. 40 ± 8 cm H₂O/L; P < 0.001).

Conclusions: ECMO was associated with better oxygenation, lower V˙V˙o₂, and better hemodynamics. ECCO₂R may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.