Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death

Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO2 ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO2/FiO2 threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO2/FiO2 (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H2O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO2 approach: (I) PaO2/FiO2 ≥ 150 at PEEP < 10, (II) PaO2/FiO2 ≥ 150 at PEEP ≥ 10, (III) PaO2/FiO2 < 150 at PEEP < 10, and (IV) PaO2/FiO2 < 150 at PEEP ≥ 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO2/FiO2 < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO2/FiO2 < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO2/FiO2 ≥ 150 (hazard ratio 2.8, 95% CI 2.2−3.5, p < 0.0001). Conclusions: Subsets based on PaO2/FiO2 thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials.