TY - JOUR
T1 - Determinants of the effect of extracorporeal carbon dioxide removal in the SUPERNOVA trial
T2 - implications for trial design
AU - for the SUPERNOVA investigators (European Society of Intensive Care Medicine trials group) and for the International ECMO Network (ECMONet)
AU - Goligher, Ewan C.
AU - Combes, Alain
AU - Brodie, Daniel
AU - Ferguson, Niall D.
AU - Pesenti, Antonio M.
AU - Ranieri, V. Marco
AU - Slutsky, Arthur S.
AU - Beale, Richard
AU - Brochard, Laurent
AU - Chiche, Jean Daniel
AU - Fan, Eddy
AU - de Backer, Daniel
AU - Francois, Guy
AU - Laffey, John
AU - Mercat, Alain
AU - McAuley, Daniel F.
AU - Müller, Thomas
AU - Quintel, Michael
AU - Vincent, Jean Louis
AU - Taccone, Fabio Silvio
AU - Peperstraete, Harlinde
AU - Morimont, Philippe
AU - Schmidt, Matthieu
AU - Levy, Bruno
AU - Diehl, Jean Luc
AU - Guervilly, Christophe
AU - Capelier, Gilles
AU - Vieillard-Baron, Antoine
AU - Messika, Jonathan
AU - Karagiannidis, Christian
AU - Moerer, Onnen
AU - Urbino, Rosario
AU - Antonelli, Massimo
AU - Mojoli, Francesco
AU - Alessandri, Francesco
AU - Grasselli, Giacomo
AU - Donker, Dirk
AU - Ferrer, Ricard
AU - Mancebo, Jordi
AU - Fanelli, Vito
AU - Pham, Tai
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Purpose: To describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design. Methods: Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland–Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population. Results: Changes in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9 cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate. Conclusions: The lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R.
AB - Purpose: To describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design. Methods: Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland–Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population. Results: Changes in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9 cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate. Conclusions: The lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R.
KW - Acute respiratory distress syndrome
KW - Artificial ventilation
KW - Extracorporeal carbon dioxide removal
KW - Predictive enrichment
KW - Ventilator-induced lung injury
UR - https://www.scopus.com/pages/publications/85070821269
UR - https://www.scopus.com/pages/publications/85070821269#tab=citedBy
U2 - 10.1007/s00134-019-05708-9
DO - 10.1007/s00134-019-05708-9
M3 - Article
C2 - 31432216
AN - SCOPUS:85070821269
SN - 0342-4642
VL - 45
SP - 1219
EP - 1230
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 9
ER -