Elevated serum levels of S-1000 protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock

Objective: We investigated whether serum levels of neuron-specific enolase (NSE) and S-100 beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. Design., Prospective study. Setting., University hospital. Patients and Measurements., In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100 beta and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. Main Results. S-100 beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p =.001), and the highest values were found in patients who died early, within 4 days of inclusion (p =.005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100 beta (p =.004). S-100 beta levels of >= 4 mu g/L were associated with severe brain ischemia or hemorrhage, and values of <2 mu g/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100 beta levels were associated with higher intensive care unit mortality (p =.04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. Conclusions., S-100 beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100 beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.