Clinical phenotypes of sepsis-associated encephalopathy: a retrospective cohort study

Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation to clinical outcomes.The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were employed to conduct a retrospective cohort study. Adult sepsis patients were included and SAE was defined as having a Glasgow Coma Scale (GCS) score ˂15, or delirium. Four clinical phenotypes were defined as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic and metabolic) and unclassified. The primary outcome was in-hospital mortality.The study enrolled 4120 sepsis patients, 2239 from MIMIC-IV (including 1489 patients with SAE, 67%) and 1881 from eICU (1291, 69%). For the SAE cohort, 2780 patients in total were enrolled (median age 67 years, interquartile range (IQR) [56, 76.8]; 1589 (57%) were male; median GCS score was 12 [8, 14]; median Sequential Organ Failure Assessment (SOFA) score was 6 [4, 9]). The SAE phenotype distributions between the MIMIC-IV and eICU cohorts were as follows (39% vs. 35% ischemic-hypoxic, p = 0.043; 38% vs. 40% metabolic, p = 0.239; 15% vs. 15% mixed, p = 0.972; 38% vs. 40% unclassified, p = 0.471). For the overall cohort, the in-hospital mortality for patients with ischemic-hypoxic, metabolic, mixed, or unclassified phenotypes was 33.9% (95% CI 0.3 - 0.37), 28.4% (0.26 - 0.31), 41.5% (0.37 - 0.46) and 14.2% (0.12 - 0.16), respectively. In the multivariable logistic analysis, the mixed phenotype was associated with the highest risk of in-hospital mortality after adjusting for age, gender, GCS and modified SOFA score (adjusted OR = 2.11, 95% CI 1.67 - 2.67, p < 0.001).Four SAE phenotypes had different clinical outcomes. The mixed phenotype had the worst outcomes. Further understanding of these phenotypes in sepsis may improve trial design and targeted SAE management.