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Cerebral dysfunctions caused by sepsis during ageing.

ABSTRACT: Systemic inflammation elicited by sepsis can induce an acute cerebral dysfunction known as sepsis-associated encephalopathy (SAE). Recent evidence suggests that SAE is common but shows a dynamic trajectory over time. Half of all patients with sepsis develop SAE in the intensive care unit, and some survivors present with sustained cognitive impairments for several years after initial sepsis onset. It is not clear why some, but not all, patients develop SAE and also the factors that determine the persistence of SAE. Here, we first summarize the chronic pathology and the dynamic changes in cognitive functions seen after the onset of sepsis. We then outline the cerebral effects of sepsis, such as neuroinflammation, alterations in neuronal synapses and neurovascular changes. We discuss the key factors that might contribute to the development and persistence of SAE in older patients, including premorbid neurodegenerative pathology, side effects of sedatives, renal dysfunction and latent virus reactivation. Finally, we postulate that some of the mechanisms that underpin neuropathology in SAE may also be relevant to delirium and persisting cognitive impairments that are seen in patients with severe COVID-19.

SUBMITTER: Manabe T

PROVIDER: S-EPMC8582341 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Cerebral dysfunctions caused by sepsis during ageing.

Manabe Tatsuya T Heneka Michael T MT

Nature reviews. Immunology 20211111 7

Systemic inflammation elicited by sepsis can induce an acute cerebral dysfunction known as sepsis-associated encephalopathy (SAE). Recent evidence suggests that SAE is common but shows a dynamic trajectory over time. Half of all patients with sepsis develop SAE in the intensive care unit, and some survivors present with sustained cognitive impairments for several years after initial sepsis onset. It is not clear why some, but not all, patients develop SAE and also the factors that determine the ...[more]

PMID: 34764472

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Project description:IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

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Cerebral dysfunctions caused by sepsis during ageing.

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Cerebral dysfunctions caused by sepsis during ageing.

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