Sepsis-associated Brain Dysfunction Research Articles

Sepsis-associated brain dysfunction in critically ill patients

Sepsis-associated brain dysfunction in critically ill patients

Pattern of Brain Injury in the Acute Setting of Human Septic Shock

BackgroundSepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change.MethodSeventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS).ResultsWe included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months.ConclusionsBrain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality.

Continuous Electroencephalography in the Medical ICU

When evaluating patients with coma or altered consciousness in non-neurological ICUs, I often wonder when I should be ordering electroencephalography (EEG). EEG is necessary to exclude non-convulsive status epilepticus but continuous EEG (cEEG) is required to assess for intermittent non-convulsive seizures. It is fairly clear that nonconvulsive epileptiform activity is relatively common in comatose critically ill neurological patients (such as patients with subarachnoid hemorrhage, intracerebral hematomas, and severe traumatic brain injury), and it is associated with worse outcomes in this population [1–3]. However, the incidence and impact of clinically occult epileptiform activity in critically ill patients without a primary brain insult has been less well defined. A recently published study by Oddo et al. [4] from Columbia University contributes to fill this gap in our knowledge. The investigators reviewed the data of 201 consecutive patients who underwent cEEG monitoring in their medical ICU. Sepsis was the primary diagnosis in 60% of the cases and 48% of the patients were comatose at the time of initiation of cEEG. Over one in five patients had electrographic seizures (ESz, present in 10%), periodic epileptiform discharges (PEDs, present in 17% and most often generalized), or both. These EEG abnormalities were not associated with any clinical manifestations (i.e., purely non-convulsive) in approximately two-thirds of cases. Sepsis was by far the most common diagnosis among patients with ESz or PEDs (84%), and they were detected in almost one-third of septic patients monitored with cEEG. In fact, sepsis was the only variable found to be independently associated with the occurrence of ESz and PEDs on cEEG (odds ratio [OR] 4.6, 95% confidence intervals [CI] 1.9–12.7, P = 0.002). Poor outcome (mortality or severe dependency) upon hospital discharge was significantly more common among patients with ESz and PEDs, even after controlling for age, coma, and organ failures (adjusted OR 19.1, 95% CI 6.3–74.6, P < 0.001). We learn from this study that ESz and PEDs are also relatively frequent in critical patients without known primary neurological injury, confirming findings from a previous cohort, which also included some neurological patients [5]. It also indicates that patients with these EEG abnormalities may have worse prognosis. However, several caveats need to be considered when interpreting the prognostic implications of this analysis. Sepsis was the only homogeneous diagnostic category considered in this study and diagnosis of sepsis was not included in the multivariable analysis evaluating predictors of outcome. Therefore, given the strong association between ESz and PEDs on cEEG and sepsis, it is possible that the association of these epileptiform abnormalities and poor outcome could be explained by the effects of sepsis. Also, the diagnosis of coma at the time of cEEG initiation was based on the exams described in the clinical records. As the level of neurological expertise of the examiners may have varied, one cannot be sure that cEEG is actually a more reliable predictor of poor outcome than the presence of coma, as it appears suggested by this study. Finally, the effect of withdrawal of life support (yes, the infamous self-fulfilling prophecy once again) may have influenced the association between cEEG findings and clinical outcome. Hence, we know that cEEG may show non-convulsive ESz and PEDs in up to one-third of selected patients with sepsis-associated brain dysfunction. We now need to

Sepsis-associated delirium

Sepsis-associated delirium is a common and poorly understood neurological complication of sepsis. This review provides an update of the diagnostic criteria and treatment strategies and the current knowledge about the mechanisms involved in sepsis associated brain dysfunction. Articles published between 1981 and 2006 were identified through a Medline search for "encephalopathy" and "sepsis" and by hand searching of articles cited in the identified publications. The immune response to sepsis results in multiorgan failure including brain dysfunction. The potential mechanisms for sepsis-associated delirium include vascular damage, endothelial activation, breakdown of the blood-brain barrier, metabolic disorders, brain inflammation and apoptosis. On the other hand, there is evidence for distinct neuroprotective factors, such as anti-inflammatory mediators and glial cell activity. The diagnosis of sepsis-associated delirium relies mainly on clinical and electrophysiological criteria, and its treatment is entirely based on general management of sepsis.