Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

Abstract

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.

Lung–kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup

“…However, permissive hypercapnia may have a negative effect on the kidney through reduced renal plasma flow and increased renal vascular resistance [119]. In theory, RRT helps compensate respiratory acidosis and may remove CO 2 through additional filters included in the CRRT circuit [extracorporeal CO 2 removal (ECCO 2 R)] [96,120,121]. While ECCO 2 R showed some benefit in a trial including 33 patients and may have aided application of ultraprotective ventilation among ARDS patients [122], another one was terminated due to insufficient CO 2 removal (PROVAP, clincialtrials.gov: NCT03004885).…”

Extracorporeal carbon dioxide removal requirements for ultraprotective mechanical ventilation: Mathematical model predictions

“…As this study was being finalized to first submit for publication, the results from the SUPERNOVA trial were published . That prospective, multicenter, international phase 2 study of 95 mechanically ventilated ARDS patients demonstrated that it is feasible to use veno‐venous ECCO 2 R to allow reductions in tidal volume from 6 to 4 mL/kg PBW without a 20% increase in PaCO 2 in approximately 80% of patients.…”

“…Overall, reductions in tidal volume to 4 mL/kg PBW with simultaneous use of ECCO 2 R maintained PaCO 2 at 46.7‐48.0 mm Hg with ventilation frequencies of 23.5‐27.4/min during the first 24 hours of treatment. A shortcoming of this trial was the inability to measure clearance and total amount of CO 2 removal by ECCO 2 R as originally planned as a secondary endpoint of that trial . We can however use the mathematical predictions in Figure to estimate the ECCO 2 R rate required to achieve approximately these same conditions (4 mL/kg PBW and ventilation frequency of 26/min) as 84 mL of CO 2 /min at a PvCO 2 of 55.6 mm Hg (neglecting the calculated ECCO 2 R rate of 3 mL of CO 2 /min at a tidal volume of 6 mL/kg PBW).…”

“…There are several ECCO 2 R devices currently available with varying abilities to remove CO 2 depending on the rate of blood flow through the device and the surface area available for transmembrane diffusion. These devices have generally been categorized as lower or higher CO 2 extraction devices with the former containing relatively small membrane surface area using blood flow rates ≤500 mL/min and the latter containing relatively large membrane surface area using blood flow rates >500 mL/min. Improvement in ECCO 2 R technologies has great potential as such devices can be integrated into a continuous renal replacement extracorporeal circuit and their efficacy for CO 2 removal may be increased by using physical principles other than diffusion such as electrodialysis or novel membrane fabrication techniques .…”

SUPERNOVA: will its energy trigger the formation of a new therapeutic star?

“…Another feasibility trial of ECCO2-R (SUPERNOVA) aiming at (ultra)-protective ventilation was recently published in Intensive Care Medicine [12]. This trial enrolled 95 patients with ARDS; the primary endpoint was the proportion of patients achieving an ultra-protective level of low VT ventilation (reduction of VT to 4 ml/kg and a target P Plat of ≤ 25 cmH 2 O) using various veno-venous ECCO2-R devices allowing extracorporeal blood flows between 300 ml/min (lower extraction) and 1000 ml/ min (higher extraction).…”