These findings suggest that encephalopathy may be a cause of death in septic patients. The encephalopathy of sepsis can be classified as either “early or septic encephalopathy,” that presents before multiple organ failure occurs or “late encephalopathy” that is accompanied by multiple organ Seliciclib mouse failure, hypotension, and other systemic phenomena. Early reports suggested that septic encephalopathy may be caused by disseminated cerebral micro-abscesses caused by septic micro-emboli but postmortem studies failed to find micro-abscesses in the brains of patients

with septic encephalopathy [2], [3] and [4]. Similar proportions of septic patients with gram-negative bacteremia, gram-positive bacteremia, fungemia or patients without an identified causative organism develop septic encephalopathy [5]. Another argument not in favour of cerebral embolism as a causative factor of septic encephalopathy is the fact that it is not associated with an increased stroke risk. These findings, together with the fact that encephalopathy occurs in noninfectious conditions such as pancreatitis, suggest that infecting organisms and/or their toxins do not directly cause encephalopathy [6]. Instead of septic micro-embolism recent studies showed that the etiology of septic encephalopathy involves a complex of factors which includes reduced cerebral blood flow and oxygen extraction by the brain, cerebral edema, and disruption of the blood

brain barrier that may arise from the action of inflammatory mediators on the cerebrovascular endothelium, abnormal neurotransmitter composition Ipilimumab datasheet of the reticular activating system, impaired astrocyte function, and neuronal degeneration [7]. Until recently no techniques were available to measure ongoing cerebral embolism in septic patients. Therefore there are no reports in the literature available

that test the hypothesis that ongoing cerebral embolisation plays no role in patients who experience a septic encephalopathy during septic shock. Due to the high Thymidine kinase temporal resolution of transcranial Doppler ultrasound (TCD) it is possible to determine accurately ongoing cerebral embolism [8]. Recently reliable automatic algorithms have been developed which facilitate embolus detection [9]. The present study has been designed to study the relation between sepsis and cerebral embolism based on the presumption that late septic encephalopathy and septic shock are not associated. To determine the incidence of ongoing cerebral embolism during a late septic encephalopathy and septic shock patients were monitored by transcranial Doppler ultrasound. The Doppler audiosignal was analysed by a recently developed and validated embolus detection system (EDS), which allows automatic detection of micro-embolic signals (MES) [10]. The final classification of the presence of cerebral embolism was done by two human experts. To rule out the presence of pre-existent active embolic sources, patients with known embolic sources were excluded.