Feasibility and safety of extracorporeal CO ₂ removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

Purpose: We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO ₂ R) to facilitate ultra-protective ventilation (V _T 4 mL/kg and P _PLAT ≤ 25 cmH ₂ O) in patients with moderate acute respiratory distress syndrome (ARDS). Methods: Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO ₂ not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO ₂ R-related adverse events (ECCO ₂ R-AE) were reported to an independent data and safety monitoring board. We used lower CO ₂ extraction and higher CO ₂ extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m ² ; flow 300–500 mL/min vs. 800–1000 mL/min, respectively). Results: Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68–89%) and 82% (78 out of 95 patients; 95% confidence interval 76–88%), respectively. ECCO ₂ R was maintained for 5 [3–8] days. Six SAEs were reported; two of them were attributed to ECCO ₂ R (brain hemorrhage and pneumothorax). ECCO ₂ R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge. Conclusions: Use of ECCO ₂ R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms. Clinicaltrials.gov: NCT02282657.