Abstract
Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.
Highlights
Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality
The purpose of this review is to provide an overview of brain dysfunction in sepsis focusing on pathophysiology, diagnosis, and potential strategies to improve neurologic outcomes
These findings suggest that sustained systemic inflammation may contribute to prolong or aggravate brain dysfunction
Summary
Numerous experimental studies suggest that these proinflammatory mediators released in the central nervous system at the onset of sepsis will in turn lead to neuronal loss within vulnerable areas of the brain, including the hippocampus [22,23,24] These findings represent a neuropathological basis for persistent cognitive impairment, hippocampal atrophy, and electroencephalographic changes observed in sepsis survivors [25]. In another study performed in 50 patients with systemic inflammatory response syndrome (SIRS), IL-8 was independently associated with delirium [56] These findings suggest that sustained systemic inflammation may contribute to prolong or aggravate brain dysfunction. The use of sedative drugs may represent a major limitation in the interpretation of clinical findings, a recent study suggested that assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status [62]. Brain MRI findings Acute changes Cytotoxic edema (hippocampus, cortex) ischemic lesions Vasogenic edema Posterior reversible encephalopathy syndrome (PRES) Chronic changes observed in survivors White matter disruption Brain atrophy (frontal cortex, hippocampus)
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