Novel cortisol trajectory sub-phenotypes in sepsis

Sepsis is a heterogeneous syndrome. This study aimed to identify new sepsis sub-phenotypes using plasma cortisol trajectory. This retrospective study included patients with sepsis admitted to the intensive care unit of Zhongshan Hospital Fudan University between March 2020 and July 2022. A group-based cortisol trajectory model was used to classify septic patients into different sub-phenotypes. The clinical characteristics, biomarkers, and outcomes were compared between sub-phenotypes. A total of 258 patients with sepsis were included, of whom 186 were male. Patients were divided into two trajectory groups: the lower-cortisol group (n = 217) exhibited consistently low and slowly declining cortisol levels, while the higher-cortisol group (n = 41) showed relatively higher levels in comparison. The 28-day mortality (65.9% vs.16.1%, P < 0.001) and 90-day mortality (65.9% vs. 19.8%, P < 0.001) of the higher-cortisol group were significantly higher than the lower-cortisol group. Multivariable Cox regression analysis showed that the trajectory sub-phenotype (HR = 5.292; 95% CI 2.218–12.626; P < 0.001), APACHE II (HR = 1.109; 95% CI 1.030–1.193; P = 0.006), SOFA (HR = 1.161; 95% CI 1.045–1.291; P = 0.006), and IL-1β (HR = 1.001; 95% CI 1.000–1.002; P = 0.007) were independent risk factors for 28-day mortality. Besides, the trajectory sub-phenotype (HR = 4.571; 95% CI 1.980–10.551; P < 0.001), APACHE II (HR = 1.108; 95% CI 1.043–1.177; P = 0.001), SOFA (HR = 1.270; 95% CI 1.130–1.428; P < 0.001), and IL-1β (HR = 1.001; 95% CI 1.000–1.001; P = 0.015) were also independent risk factors for 90-day mortality. This study identified two novel cortisol trajectory sub-phenotypes in patients with sepsis. The trajectories were associated with mortality, providing new insights into sepsis classification.