Review
Cognitive decline after sepsis

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Summary

The modern era of sepsis management is characterised by a growing number of patients who survive in the short term and are discharged from hospital. Increasing evidence suggests that these survivors exhibit long-term neurological sequelae, particularly substantial declines in cognitive function. The exact prevalence and outcomes of these neuropsychological sequelae are unclear. The mechanisms by which sepsis induces cognitive dysfunction probably include vascular injuries and neuroinflammation that are mediated by systemic metabolism disorders and overwhelming inflammation, a disrupted blood–brain barrier, oxidative stress, and severe microglial activation, particularly within the limbic system. Interventions targeting the blood–brain barrier, glial activation, and oxidative stress have shown promise in prevention of cognitive dysfunction in various experimental models of sepsis. The next step should be to translate these favourable effects into positive clinical results.

Section snippets

Background

Sepsis—when an infection is complicated with systemic inflammation-induced organ dysfunction or tissue hypoperfusion—is a major challenge for physicians worldwide because of the uncontrollable increase in its annual incidence, major gaps in understanding of its pathophysiology, repeated failures in the development of specific treatments, and long-term and substantial sequelae after its survival. Irrespective of a country's growth, income, products, and geographical location, and irrespective of

Overview

The CNS plays a major part in maintenance of homoeostasis during stress, mainly via the autonomic nervous system and hypothalamic–pituitary–adrenal axis. Inappropriate brain responses might favour cardiovascular instability, metabolic disorders, and a sustained pro-inflammatory state, which, in turn, might irreversibly damage the brain (figure 1). Moreover, several ICU interventions might directly and indirectly exacerbate brain injuries.

Cerebrovascular damage

Abrupt variations in systemic blood pressure are frequent

Clinical presentation

The clinical manifestations of cognitive impairment can be noted in the initial phase of sepsis, at recovery from the initial phase, and long term after hospital discharge. The acute phase of sepsis is characterised by so-called sickness behaviour, which is an evolutionarily acquired syndrome that increases withdrawn behaviour and allows the host to focus on fighting the infection. This syndrome typically includes withdrawal from social activities, anxiety, anorexia and bodyweight loss,

Non-specific interventions

Optimisation of initial management of patients with sepsis prevents brain injuries and subsequent declines in cognitive function. Appropriate implementation of the updated Surviving Sepsis campaign guidelines77 is associated with important reductions in short-term and long-term mortalities.78 Thus far, the potential benefits of implementing these guidelines on the risk of developing cognitive impairment have not been assessed. Findings from a single-centre case-control study31 using electronic

Implications for practice and research

Arguably, the available evidence in the literature favours screening of sepsis survivors at times of ICU and hospital discharge with the 3MS test. Patients with abnormal 3MS test results should then be considered for more comprehensive analyses using, for example, the Repeatable Battery for the Assessment of Neuropsychological Status method, and might be referred to memory clinics for long-term follow-up. Thus far, therapeutic options are limited to optimisation of initial management of

Search strategy and selection criteria

We identified references for this Review through searches of PubMed with no date or language restrictions, with the latest date of the search as July 31, 2014. We used the terms “sepsis”, “encephalopathy”, “delirium”, “mental status”, “cognition”, “cognitive function”, “dementia”, “neurodegenerative disorders”, “human studies”, and “animal studies”. We analysed the full texts of all articles deemed to be relevant to this Review on the basis of titles and abstracts. We also searched the

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