The Diagnosis of Sepsis-Associated Encephalopathy Using Biomarkers: Are We There Yet?

Abstract

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs in patients with sepsis in the absence of direct central nervous system infection or other causes of encephalopathy. SAE is common, occurring in up to 70% of patients with sepsis, and is linked to various clinical manifestations and significantly poorer outcomes. The diagnosis of SAE usually relies on clinical examination, which is often difficult due to confounding factors in critically ill patients. Other diagnostic tools used include electroencephalography, neuroimaging, and biomarkers. We performed a systematic search and review to synthesize all available evidence on biomarkers used for SAE diagnosis in clinical practice and highlight future directions for research. The literature search in MEDLINE identified 18 eligible studies. Biomarkers reflecting inflammation, endothelial activation and damage, astrocytic and microglial activation, neuronal injury, and metabolism changes were described, demonstrating their usefulness and potential in diagnosing and evaluating SAE. However, among different studies, the reported sensitivity and specificity of the biomarkers for diagnosing SAE varied based on the populations studied and the cutoff levels considered for each biomarker. In conclusion, biomarkers may be useful for diagnosing and predicting outcomes in SAE, but their usefulness in clinical practice remains limited for the moment. More research is needed to identify biomarkers that can improve SAE diagnosis.

Keywords

encephalopathy - sepsis - biomarkers - diagnosis

Ethics Approval and Consent

Not applicable.

Data, Materials, and/or Code availability

This published article and its supplementary information files include all data generated or analyzed during this study.

Authors' Contributions

All the authors contributed to the study's conception and design. F.S. and E.S. performed the literature search and data analysis and wrote the first draft. All the authors read and critically revised the work, and approved the final manuscript.

Publication History

Article published online:
06 May 2025

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