Sepsis-induced brain dysfunction

Abstract

Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

Incidence and risk factors for delirium development in ICU patients - a prospective observational study

“…It may be the next explanation of the small incidence of delirium in our study compared with the results of some other studies. It is widely accepted that one of the most common causes of delirium in medical intensive care units is sepsis [11][12][13][14][15] . One of the earliest changes during sepsis, due to pro-inflammatory cytokines, is microglial activation which in turn leads to neuronal loss.…”

“…One of the earliest changes during sepsis, due to pro-inflammatory cytokines, is microglial activation which in turn leads to neuronal loss. Oxidative stress, mitochondrial dysfunction with mitochondrial-mediated apoptosis, impaired cerebral perfusion and persistent hyperglycaemia are other important mechanisms that may induce brain dysfunction [12][13][14][15][16][17][18][19] . Neurotransmitter imbalance, especially between dopaminergic and cholinergic neurotransmission, seems to play a significant role and there are other significant neurotransmitters (beta-adrenergic substances, gamma-aminobutyric acid, serotonergic agents) whose alterations affect the development of delirium 1,11 .…”

“…Delirium indicates an acute cerebral failure. Its pathophysiology is highly complex, resulting from both inflammatory and non-inflammatory processes 1,[11][12][13][14][15][16][17][18][19] . Delirium is never caused by a single factor.…”

Could Biomarkers Direct Therapy for the Septic Patient?

“…While the pathophysiology is still poorly understood, neuroinflammatory and ischemic processes are likely contributors to alterations in the blood-brain barrier, release of neurotoxic mediators, and microglial activation (Adam et al, 2013). Changes in standard electroencephalogram are associated with increased mortality and delirium in septic intensive care unit patients (Azabou et al, 2015).…”

Diagnostic tools and therapeutic end-points in critical care medicine: Limitations and concepts

“…The therapeutic action is to infuse a vasopressor, aiming to increase blood pressure and preserve renal flow (as assessed through the urine output) and cerebral flow (as assessed through the level of consciousness). Nonetheless, an integrative approach to the patient must distinguish renal injury or septic encephalopathy [42] , both confounding the situation, but relying on clinical assessment [43,44] .…”