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.
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.