Sepsis Associated Encephalopathy

Neera Chaudhry, Ashish Kumar Duggal, Neera Chaudhry, Ashish Kumar Duggal

Abstract

Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

Figures

Figure 1
Figure 1
Pathophysiology of sepsis associated encephalopathy. Altered brain signalling during sepsis occurring as a result of centrally and peripherally acting cytokines results in production of various inflammatory cytokines that cause activation of various behavioral, neuroendocrine, and neurovegetative centers which can cause altered behaviour. In addition these cytokines cause microglial activation thus perpetuating the production of inflammatory cytokines and reactive oxygen species. Peripherally produced LPS, cytokines, and NO cause further damage to the BBB thereby causing a vicious cycle of brain damage. The excessive production of LPS and cytokines causes increased production of NO and other ROS thereby causing mitochondrial dysfunction and apoptosis. Altered amino acid balance because of excessive muscle proteolysis is responsible for production of false neurotransmitters which can also contribute to the pathogenesis of SAE. Disturbed cerebral autoregulation and direct cerebral localization may play a minor role. NO: nitrous oxide, ROS: reactive oxygen species, LPS: lipopolysaccharide, TNF-α: tumor necrosis factor-α, AAA: aromatic amino acids, and BBB: blood brain barrier.
Figure 2
Figure 2
Algorithm for diagnosis of sepsis associated encephalopathy. RASS: Richmond Agitation-Sedation Scale, FOUR: Full Outline of Unresponsiveness, GCS: Glasgow coma scale, SEP: somatosensory evoked potentials, NSE: neuron specific enolase, CAM/CAM-ICU: Confusion Assessment Method (Intensive Care Unit), and ATICE: Assessment to Intensive Care Environment.

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