We searched Pubmed and OVID CINAHL, with the key words “sepsis”, “long-term outcome”, “neurocognitive”, and “neuroinflammation”. Additional terms used in the search were: “activities of daily living”, “apoptosis”, “autopsy”, “brain damage”, “brain death”, “brain dysfunction”, “brain imaging”, “cerebral consequences”, “cerebral sequelae”, “cognition”, “cognitive”, “EEG”, “intelligence”, “long-term outcome”, “MRI”, “neurocognitive”, “neuropsychology”, “necrosis”, “neurodegeneration”,
Personal ViewLong-term cerebral consequences of sepsis
Introduction
Sepsis, also known as endotoxaemia, or blood poisoning, is defined as a whole-body systemic inflammatory state and the simultaneous occurrence of a suspected or diagnosed infection. Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. The prevalence of sepsis in the USA is three per 1000 people; more than half of these patients need treatment at an intensive care unit (ICU), and the overwhelming majority die within 5 years after having had sepsis, despite increases in short-term survivorship in the last two decades.1, 2 Sepsis with its complications is a leading cause of mortality among ICU patients, and accounts for 10–50% of deaths. A major symptom of sepsis is sepsis-associated encephalopathy, which is a rapid decline in cognitive functions, especially memory. Sepsis-associated encephalopathy, which typically manifests as confusion or coma, is reported in up to 70% of patients with sepsis.3, 4 People who have survived sepsis, especially those who have had sepsis-associated encephalopathy, warrant special attention because new evidence has emerged that many of them never fully recover.5, 6, 7 Unfortunately, these patients can fall through the gaps after successful acute care, since they are not followed up by intensive care doctors, and are unlikely to consult a neurologist. Sepsis-associated encephalopathy is an especially timely topic because new findings about clinical outcomes of sepsis survivors dovetail with studies that have identified infectious disease and systemic inflammation as risk factors for delirium, cognitive impairment, and neurodegenerative diseases.8, 9, 10, 11, 12, 13, 14
Because the long-term cognitive and cerebral consequences of sepsis-associated encephalopathy are not well understood, key opportunities for neuroprotective interventions and much-needed after-care support for people who have survived sepsis might be lost. The social and tragic personal costs of sepsis might appreciably be reduced if interventions and therapies for patients who have had sepsis were put into place.15, 16, 17 Furthermore, evidence of long-term neurocognitive impairment and brain dysfunction in people who have survived sepsis should gain more attention in the neurological community. This Personal View meets what we regard as a pressing need to combine what is known about the mechanisms and pathogenesis that underlie sepsis-associated encephalopathy, longitudinal findings from ICUs about patients with sepsis, and developments in dementia studies. We outline the best-understood mechanisms that might underlie cerebral damage, neuronal damage and death, and long-term neurocognitive impairment in people who have survived sepsis and sepsis-associated encephalopathy. We also review the evidence of cerebral damage and long-term cognitive impairment in people who have survived sepsis. In doing so, we have the following aims: to stimulate discovery of neuroprotective interventions during the acute stage of disease; to encourage fellow clinicians to monitor the recovery of sepsis survivors more closely; and to request that fellow researchers investigate possible connections between sepsis and the subsequent development of neurodegenerative diseases.
Section snippets
Mechanisms of neuronal damage in sepsis-associated encephalopathy
Among the far-reaching and sustained systemic effects of sepsis is hyperdynamic circulation, which also causes the changes in cerebral blood flow that are implicated in sepsis-associated encephalopathy. Although reduced cerebral blood flow and oxygenation occur in sepsis, they do not appear to drop low enough to threaten neuronal viability or cause electroencephalogram (EEG) changes in preclinical models of sepsis-associated encephalopathy. This assumption is reasonable, because cerebral blood
Analyses of neurocognitive function and dementia
To date, the long-term consequences of sepsis in human beings have been examined in only a handful of reported studies, all of which underscore the connection between sepsis-associated encephalopathy and subsequent cognitive decline and possibly neurodegenerative disease.5, 6, 7, 13, 60, 61 Mild-to-moderate neurocognitive deficits consistently occur in a proportion of people who survive sepsis; these deficits persist for years after hospital release, and seem to be newly acquired (ie, they were
Conclusions and future directions
A substantial proportion of people who survive sepsis develop diffuse long-term cognitive deficits, and seem to have an increased risk of developing dementia. The initial processes involved in sepsis-associated encephalopathy, such as reduced cerebral blood flow, weakened blood–brain barrier, neuronal dysfunction and death, sustained microglia activation, impairment of microcirculation, and endothelial injury and dysfunction, could also lead to permanent cerebral damage. Some key questions
Search strategy and selection criteria
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