Table 1 Limitations of the current definition and diagnostic/therapeutic approach of ARDS
Bilateral and diffuse pulmonary edema | Lack of a marker of non-cardiogenic origin of pulmonary edema |
Lack of a (bio)marker of pulmonary vascular permeability | |
Oxygenation | A single measurement of PaO2/FiO2 at ARDS onset or diagnosis has poor performance for definition or predicting severity |
Lack of standardization of respiratory support settings for measuring PaO2/FiO2 | |
Difficult to distinguish ARDS from acute hypoxemic respiratory failure since clinical features and etiologic causes are similar | |
Lung mechanics | Not required in the current definition |
Missing dead space (VD/VT) measurement in definition and progression | |
Hard to conceive a mechanically ventilated ARDS patient receiving PEEP ≤ 5 cmH2O | |
Systemic inflammation | Definition and categorization do not account for non-pulmonary organ failure, which is present in most patients and a major determinant of outcome |
Too much emphasis on the alveolar side. Little consideration for the pulmonary vascular and endothelial side, presence of pulmonary hypertension or right ventricular function | |
Systemic inflammation seen in ARDS based on protein and mRNA biomarkers is not specific for ARDS, especially in septic patients | |
Categorization and sub-phenotyping | Missing stratification in sub-phenotypes based on VD/VT, endothelial injury, biomarker levels, or modifiable or treatable traits |
It is highly plausible that in a substantial proportion of patients in recent trials, the severity of lung injury was modest | |
Mechanical ventilation setting | It should be personalized based on etiology, lung physiology, imaging and morphology, and clinical and biological classes or subclasses |
In some ARDS trials, unselected patients could be enrolled missing the opportunity to test whether the experimental MV approach is beneficial due to lack of standardized assessment of severity prior to randomization and to lack of patient sub-phenotyping |