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Efficacy and safety of lower versus higher CO Retrospective analysis of the SUPERNOVA trial exploring the hypothesis that efficacy and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate reduction of tidal volume (VT) to 4 mL/kg in patients with acute respiratory distress syndrome (ARDS) may differ between systems with lower (area of membrane length 0.59 m2; blood flow 300-500 mL/min) and higher (membrane area 1.30 m2; blood flow between 800 and 1000 mL/min) CO2 extraction capacity. Ninety-five patients with moderate ARDS were included (33 patients treated with lower and 62 patients treated with higher CO2 extraction devices). We found that (1) VT of 4 mL/kg was reached by 55% and 64% of patients with the lower extraction versus 90% and 92% of patients with higher extraction devices at 8 and 24 hours from baseline, respectively (p<0.001), and (2) percentage of patients experiencing episodes of ECCO2R-related haemolysis and bleeding was higher with lower than with higher extraction devices (21% vs 6%, p=0.045% and 27% vs 6%, p=0.010, respectively). Although V T of 4 mL/kg could have been obtained with all devices, this was achieved frequently and with a lower rate of adverse events by devices with higher CO2 extraction capacity.