Assessment of brain dysfunction and delirium using serum biomarkers of brain injury and contrast-enhanced ultrasound imaging in circulatory shock and septic shock.

Brain dysfunction and delirium are common complications of sepsis and shock, and multiple risk factors are implicated in the pathogenesis. In this thesis, different precipitating risk factors of the development of brain dysfunction and therapeutic options have been investigated. We show that elevation of the biomarkers of brain injury S100B and neuron-specific enolase is associated with the development of brain injury and worse outcome in sepsis. We show that excessive release of the stress hormones cortisol and prolactin is associated with the development of brain dysfunction and delirium in sepsis. We show that the degree and the recurrence of hypotension, and excessive fluid administration but not extracorporeal membrane oxygenation treatment, can promote the development of delirium. Using contrast-enhanced ultrasound imaging we demonstrate that brain microcirculation is early altered in sepsis We also observe that administration of vasopressin or drotrecogin alpha (activated) as adjunctive treatment can respectively reverse shock and reduce the serum levels of S100B in sepsis.