Consensus-derived clinical sepsis profiles and mortality across six international cohorts

Clinical phenotyping may help characterize sepsis heterogeneity, but the applicability of derived profiles across healthcare settings remains uncertain. We evaluated consensus-derived clinical profiles and their associations with mortality across six international cohorts.

We analyzed 62,458 adults from six critical care databases in four countries. In the MIMIC-IV discovery cohort (n = 28,733), six clustering algorithms were applied to 24 routinely available clinical variables to derive consensus profiles. The profiles were assigned in five external cohorts using fixed discovery-cohort templates. We examined clinical characteristics, mortality associations, and exploratory treatment-outcome associations.

Three profiles were selected based on the Calinski-Harabasz peak and clinical interpretability. Profiles 1, 2, and 3 comprised 32.6%, 20.0%, and 47.4% of the discovery cohort, with in-hospital mortality of 30.3%, 13.8%, and 9.3%, respectively. Profile 1 showed greater multiorgan dysfunction, Profile 2 relatively preserved hemodynamics, and Profile 3 greater ventilatory support with less extrapulmonary dysfunction. Profile 1 had the highest mortality in all five external cohorts, with a decreasing mortality gradient across profiles in most cohorts. After adjustment for age and SOFA score, Profile 3 was associated with lower 1-year mortality than Profile 1 (hazard ratio 0.62, 95% CI 0.57-0.67). Treatment-outcome associations were exploratory.

Consensus-derived profiles characterized clinically interpretable patterns of sepsis heterogeneity with mortality differences across the evaluated cohorts. These findings support further evaluation of clinical profiling for risk stratification and phenotype-informed research.