Identification of novel sub-phenotypes of severe ARDS requiring ECMO using latent class analysis

Sub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). We conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes. We identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036). The three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.