Current knowledge and challenges of sepsis-associated encephalopathy

Abstract: Encephalopathy is a common complication of sepsis, occurring in up to 70% of patients admitted to the intensive care unit. It is primarily characterized by a deterioration in condition, ranging from delirium to coma, but also by electroencephalographic changes and seizures. Sepsis-associated encephalopathy (SAE) is linked to increased mortality, which rises in proportion to the severity of both clinical manifestations and electroencephalographic abnormalities, and is frequently followed by long-term cognitive impairment and functional disability. The pathophysiology of SAE is complex and includes a disturbance in neurotransmission together with a dysfunction of different brain cells and functional complexes (blood–brain barrier, neurovascular coupling, synapses). Neuroinflammation and ischemia are its main processes. Its cellular mechanisms include bioenergetic failure and oxidative stress. The frontal cortex, hippocampus, limbic system, and brainstem are particularly vulnerable to these events. Currently, management relies primarily on controlling sepsis and applying recommendations for delirium, including the avoidance of neurotoxic agents. Developing a specific treatment would depend on a better understanding of its pathophysiology, through a relevant experimental model, as well as on the identification of biomarkers with diagnostic, pathophysiological, and/or prognostic value. This contemporary review synthesizes current data on the epidemiology, mechanisms, characteristics and complications of SAE, as well as priorities for therapeutic progress. Graphic abstract: (Figure presented.)