Determinants of Effect of Extracorporeal CO ₂ Removal in Hypoxemic Respiratory Failure

BackgroundDead space and respiratory system elastance (Ers) may influence the clinical benefit of a ventilation strategy combining very low tidal volume (VT) with extracorporeal carbon dioxide removal (ECCO2R) in patients with acute hypoxemic respiratory failure. We sought to evaluate whether the effect of ECCO2R on mortality varies according to ventilatory ratio (VR; a composite variable reflective of dead space and shunt) and Ers.MethodsSecondary analysis of a trial of a strategy combining very low VT and low-flow ECCO2R planned before the availability of trial results. Bayesian logistic regression was used to estimate the posterior probability of effect moderation by VR, Ers, and severity of hypoxemia (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen [PaO2:FiO2]) on 90-day mortality. Credibility of effect moderation was appraised according to the Instrument for Assessing the Credibility of Effect Modification Analyses criteria.ResultsA total of 405 patients were available for analysis. The effect of the intervention on mortality varied substantially with VR (posterior probability of interaction, 94%; high credibility). Benefit was more probable than harm in patients with VR 3 or higher. In patients with VR less than 3, the probability of increased mortality with intervention was high (>90%). The effect of the intervention also varied with PaO2:FiO2 (posterior probability of interaction, >99%; low credibility). Benefit was more probable than harm in patients with PaO2:FiO2 110 mm Hg or higher. The effect of the intervention did not vary substantially with Ers (posterior probability of interaction, 68%; low credibility).ConclusionsVR has a highly credible influence on the effect of a strategy combining very low VT and low-flow ECCO2R on mortality. This intervention may reduce mortality in patients with high VR. (Funded by an Early Career Investigator Award from the Canadian Institutes of Health Research to Dr. Goligher.)