Xin Lu, Mubing Qin, Joseph Harold Walline, Yanxia Gao, Shiyuan Yu, Zengzheng Ge, Chao Gong, Huadong Zhu, Djillali Annane, Yi Li

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: 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. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were used 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. The following our clinical phenotypes were defined as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic and metabolic), and unclassified. The primary outcome was in-hospital mortality. Results: The study enrolled 4,120 sepsis patients, 2,239 from MIMIC-IV (including 1,489 patients with SAE, 67%), and 1,881 from eICU (1,291, 69%). For the SAE cohort, 2,780 patients in total were enrolled (median age, 67 years; interquartile range, 56-76.8; 1,589 (57%) were male; median GCS score was 12 [8-14]; median Sequential Organ Failure Assessment 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% confidence interval, 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, sex, GCS, and modified Sequential Organ Failure Assessment score (adjusted odds ratio, 2.11; 95% confidence interval, 1.67-2.67; P < 0.001). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
Issue number4
StatePublished - Apr 1 2023

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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