Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review

Abstract

Sepsis-associated encephalopathy (SAE) is one of the most common types of organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae, its mortality in patients diagnosed with sepsis, progressing to SAE, is 9% to 76%. The pathophysiology of SAE is still unknown, but its mechanisms are well elaborated, including oxidative stress, increased cytokines and proinflammatory factors levels, disturbances in the cerebral circulation, changes in blood–brain barrier permeability, injury to the brain’s vascular endothelium, altered levels of neurotransmitters, changes in amino acid levels, dysfunction of cerebral microvascular cells, mitochondria dysfunction, activation of microglia and astrocytes, and neuronal death. The diagnosis of SAE involves excluding direct CNS infection or other types of encephalopathies, which might hinder its early detection and appropriate implementation of management protocols, especially in paediatric patients where only a few cases have been reported in the literature. The most commonly applied diagnostic tools include electroencephalography, neurological imaging, and biomarker detection. SAE treatment mainly focuses on managing underlying conditions and using antibiotics and supportive therapy. In contrast, sedative medication is used judiciously to treat those showing features such as agitation. The most widely used medication is dexmedetomidine which is neuroprotective by inhibiting neuronal apoptosis and reducing a sepsis-associated inflammatory response, resulting in improved short-term mortality and shorter time on a ventilator. Other agents, such as dexamethasone, melatonin, and magnesium, are also being explored in vivo and ex vivo with encouraging results. Managing modifiable factors associated with SAE is crucial in improving generalised neurological outcomes. From those mentioned above, there are still only a few experimentation models of paediatric SAE and its treatment strategies. Extrapolation of adult SAE models is challenging because of the evolving brain and technical complexity of the model being investigated. Here, we reviewed the current understanding of paediatric SAE, its pathophysiological mechanisms, diagnostic methods, therapeutic interventions, and potential emerging neuroprotective agents.

Septic encephalopathy in the elderly – biomarkers of potential clinical utility

“…EEG can exclude or confirm non-convulsive status epilepticus which requires treatment with antiepileptics ( Pantzaris et al, 2021 ). The specificity of EEG for the diagnosis of septic encephalopathy is low, and sedatives can mimic abnormalities encountered in severe septic encephalopathy ( Dumbuya et al, 2023 ).…”

“…They are less susceptible to sedation, but the recording of SEPs is cumbersome in intensive care units. Slowing of SEP latencies has been described in septic encephalopathy, but data correlating SEPs with outcome are sparse ( Tauber et al, 2021 ; Dumbuya et al, 2023 ).…”

“…The most extreme manifestation of septic encephalopathy occurs in deep septic shock with bilateral hippocampal necrosis as a consequence of watershed infarctions ( Tauber et al, 2017 ). Pathophysiological mechanisms have been discussed in detail in several recent publications ( Perry et al, 2003 ; Tauber et al, 2017 , 2021 ; Robba et al, 2018 ; Too et al, 2021 ; Sekino et al, 2022 ; Dumbuya et al, 2023 ; Barichello et al, 2023 ; Piva et al, 2023 ). This review will focus on biomarkers of septic encephalopathy which have already been successfully applied in clinical practice and which show promise as prognostic markers in older patients.…”

Application of magnetic resonance imaging-related techniques in the diagnosis of sepsis-associated encephalopathy: present status and prospect

“…Although scholars have conducted a series of studies on SAE pathogenesis and acquired some findings, the early diagnosis of SAE is still a major clinical problem, which remains an exclusionary diagnosis ( Dumbuya et al, 2023 ). The clinical manifestations of SAE range from mild consciousness disorders to delirium, deep coma, or seizures and cognitive and emotional dysfunction ( Stubbs et al, 2013 ; Gao and Hernandes, 2021 ).…”

Molecular Pathways in Sepsis Pathogenesis: Recent Advances and Therapeutic Avenues

“…Cognitive impairment, including memory deficits and executive dysfunction, can persist even after recovery from sepsis [39]. These neurological consequences can have long-term impacts on patients' quality of life [40]. Respiratory consequences are also frequently encountered in sepsis.…”