Septic-Associated Encephalopathy: a Comprehensive Review

Abstract

Septic-associated encephalopathy (SAE) is a key manifestation of sepsis, ranging from delirium to coma and occurring in up to 70% of patients admitted to the ICU. SAE is associated with higher ICU and hospital mortality, and also with poorer long-term outcomes, including cognitive and functional outcomes. The pathophysiology of SAE is complex, and it may involve neurotransmitter dysfunction, inflammatory and ischemic lesions to the brain, microglial activation, and blood-brain barrier dysfunction. Delirium (which is included in the SAE spectrum) is mostly diagnosed with validated scales in the ICU population. There is no established treatment for SAE; benzodiazepines should generally be avoided in this setting. Nonpharmacological prevention and management is key for treating SAE; it includes avoiding oversedation (mainly with benzodiazepines), early mobilization, and sleep promotion.

Keywords: Sepsis; blood–brain barrier; microglia; neuroanatomy; neuroinflammation; sepsis-associated encephalopathy.

Fig. 1

Schematic view of the different pathophysiological processes observed or supposed during sepsis-associated encephalopathy. Vascular changes include blood–brain barrier dysfunction, neurovascular uncoupling, and strokes. Neuroinflammation includes microglial and astrocytic activation enhancing excitotoxicity and metabolic imbalance inducing neuronal cell death

Fig. 2

Early signs observed during sepsis (upper row), relying on specific structures (middle row) and associated with worst outcome (right row). Sickness behavior is considered as a physiological response to systemic inflammation; delirium and consciousness disorders are clinical signs of SAE. SAE = sepsis-associated encephalopathy, PTSD = posttraumatic stress disorder

Fig. 3

Scheme for the response to stress network mobilization during sepsis. The peripheral inflammation signal is transmitted to the CNS through 3 main pathways (dark blue arrows) activating specific structures (light blue arrows), the circumventricular organs (CVO), or the vagus nerve nuclei. Behavioral, neuroendocrine, and autonomic structures are interconnected and stimulated, leading to the functional response (dark green arrows and rectangles). CNS = central nervous system, CVO = circumventricular organs, BBB = blood–brain barrier