Critical illness: the brain is always in the line of fire

Abstract

Life-threatening systemic insults or diseases often affect the brain. In critically ill patients, acute brain dysfunction manifests in several ways including reduced consciousness, coma, or delirium. The pathophysiology is complex, incompletely understood, and may relate to critical illness-related inflammatory changes, neurotransmitter imbalances, or failure of adequate energy substrate delivery [1], as well as to the applied treatments, pharmacological neurotoxicity, or the hostile ICU environment (Fig. 1) [2].Delirium warrants some emphasis because it is the most common manifestation of critical illness-related brain dysfunction [3]. In a recent study of 420 critically ill mechanically ventilated adult patients, 54% experienced delirium for at least 1 day (median delirium duration 2 days, interquartile range 1-4 days) [4]. The hippocampus and frontal cortex, both areas that are extremely vulnerable to metabolic and hypoxic-ischemic insults, appear to be predominantly involved. Triggers of ICU delirium include predisposing factors (older age, previous cognitive impairment, arterial hypertension), precipitating factors (mainly related to the severity of critical illness), and factors that can potentially be treated or avoided including medications (benzodiazepines, opioids, and anticholinergics), pain, sepsis, fever, metabolic disturbances (dysglycemia, dysnatremia), and environmental factors (sleep deprivation, noisy environment).An acute encephalopathy is reported in up to 70% of patients with sepsis. Systemic insults, such as hemodynamic changes leading to impaired cerebral perfusion, severe hypoxemia, endocrine dysfunction, or fever, are aggravated by blood-brain barrier dysfunction, impairment of the cerebral microcirculation, microglial activation by pro-and anti-inflammatory cytokines and chemokines, and altered neurotransmission [5]. In some cases this can lead to cerebral edema, ischemia, or seizures.The electroencephalography (EEG) findings of sepsisrelated encephalopathy are characterized by a diffuse cortical dysfunction with generalized EEG slowing and the presence of theta and delta waves [3]. Seizures in sepsis are often non-convulsive in nature and require EEG monitoring for their identification. A recent single-center study identified a high incidence of non-convulsive seizures (11%) and periodic discharges (25%) in a cohort of patients with sepsis-related alterations in mental status, although this was not associated with a higher mortality or disability rates at 6 and 12 months after discharge [6]. However, loss of EEG reactivity to external stimulation, a sign of severe encephalopathy, was associated with increased mortality in this patient cohort. Large, prospective studies are required to determine the outcome effects of EEG abnormalities in the critically ill septic patient and whether their treatment modulates outcomes.Critical illness-related brain dysfunction is associated with worse short-term outcomes, such as longer duration of mechanical ventilation and increased ICU and hospital l...

Mortality Predictors and Associated Factors in Patients in the Intensive Care Unit: A Cross-Sectional Study

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JAK/STAT signaling pathway-mediated microRNA-181b promoted blood-brain barrier impairment by targeting sphingosine-1-phosphate receptor 1 in septic rats

“…Some studies have demonstrated that injury to the blood-brain barrier (BBB) plays a key role in the pathophysiological mechanism of SAE (3,4). Annane and Sharshar (3) demonstrated that interventions targeting the blood-brain barrier have shown promise in prevention of cognitive dysfunction in various experimental models of sepsis.…”

Epileptic seizure discharges in patients after open chamber cardiac surgery—a prospective prevalence pilot study using continuous electroencephalography

“…Furthermore, patients presenting electrographic seizures tended to have lower MMSE level prior to surgery, though this did not reach statistical significance. Both age and preexisting cognitive impairment are well-known risk factors for delirium in ICU patients [13]. It should be discussed whether both entities-seizures and deliriummay be independent consequences of major surgery on an aged and potentially already impaired brain.…”