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Published on: April 7, 2021
Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of
Jesús Villar1,2,3, Cristina Fernández2, Jesús M González-Martín1,2
1CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Abstract:
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.
Insights
A 24-hour PaO2/FiO2 ratio threshold of 150 mm Hg in acute respiratory distress syndrome (ARDS) patients predicts intensive care unit (ICU) mortality. This ARDS classification improves prognostication and aids in selecting therapies and trial enrollment.
Area of Science:
- Critical Care Medicine
- Pulmonary Medicine
- Respiratory Physiology
Background:
- The PaO2/FiO2 ratio at acute respiratory distress syndrome (ARDS) diagnosis has limited predictive value for mortality.
- Lung-protective ventilation strategies are standard for ARDS management.
- Accurate prognostication is crucial for guiding treatment intensity and clinical trial enrollment in ARDS.
Purpose of the Study:
- To evaluate the hypothesis that a PaO2/FiO2 ratio threshold of 150 mm Hg at 24 hours post-ARDS diagnosis improves prediction of intensive care unit (ICU) mortality.
- To assess the clinical relevance of patient subsets defined by PaO2/FiO2 and positive end-expiratory pressure (PEEP) levels for prognostication.
Main Methods:
- An ancillary study involving 1303 patients with moderate to severe ARDS managed with lung-protective ventilation across four prospective multicenter cohorts.
- Patients were classified into four subsets based on PaO2/FiO2 (150 mm Hg) and PEEP (10 cm H2O) thresholds at baseline and 24 hours.
- Two cohorts were pooled as a testing set (n=1000) and one as a confirmatory set (n=303).
Main Results:
- ICU mortality rates were similar between the testing (37.5%) and confirmatory (37.0%) cohorts.
- At baseline, PaO2/FiO2 < 150 mm Hg was common (79.2%), with no significant mortality difference among subsets (p=0.23).
- At 24 hours, ICU mortality significantly increased across subsets defined by PaO2/FiO2 and PEEP (p < 0.0001), with findings replicated in the confirmatory cohort.
- Patients with PaO2/FiO2 < 150 mm Hg at 24 hours had significantly worse 30-day ICU survival (Hazard Ratio 2.8, p < 0.0001), independent of PEEP levels.
Conclusions:
- Patient subsets defined by a 24-hour PaO2/FiO2 threshold of 150 mm Hg are clinically relevant for predicting ICU mortality in moderate/severe ARDS.
- This classification aids in identifying patients who may benefit from adjunctive therapies for hypoxemia.
- The 24-hour PaO2/FiO2 threshold is valuable for patient selection in therapeutic trials for ARDS.
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