Compliance Phenotypes in Early Acute Respiratory Distress Syndrome before the COVID-19 Pandemic

Rationale: A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype. Objectives: To determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs-mortality relationship. Methods: We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes. Measurements and Main Results: Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23-40) ml/cm H2O. One hundred thirty-six (12%) patients had preserved Crs (>= 50 ml/cm H2O; phenotype with low elastance ["phenotype L"]), and 827 (74%) patients had poor Crs (<40 ml/cm H2O; phenotype with high elastance ["phenotype H"]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P<0.05). A near complete dissociation between PaO2/FIO2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a PaO2/FIO2, <150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H2O increase, 0.988; 95% confidence interval, 0.979-0.996; P = 0.005). Conclusions: A wide range of Crs was observed in non-COVID-19 ARDS. Approximately one in eight patients had preserved Crs. PaO2/FIO2 and Crs were dissociated. Lower Crs was independently associated with higher mortality. The Crs-mortality relationship lacked a clear transition threshold.