Matt Harmon

19 Chapter one Outline of this thesis Part I: Spontaneous hypothermia in sepsis Chapter 2: We characterized differences in definition and rewarming practices of spontaneous hypothermia during sepsis among physicians in an online survey. We also assessed current opinions on the etiology and treatment of rewarming patients with spontaneous hypothermia during sepsis. Chapter 3: In a prospective observational study, risk factors for spontaneous hypothermia in sepsis were identified. We also studied the host immune response and markers of endothelial activation. The hypothesis was that patients with spontaneous septic hypothermia could not generate an adequate host immune response and that parameters of endothelial to determine the etiology of the hypothermic response. Chapter 4: We analyzed whole-genome transcriptome in leukocytes. The hypothesis was that canonical specific signaling pathways in spontaneous hypothermia in sepsis differed from non-hypothermic patients. This study was done in order to generate new hypotheses towards the etiology of the hypothermic response. Part II: Induced normothermia in human endotoxemia Chapter 6: We used a human endotoxemia model to study the effects of induced normothermia on physiologic parameters and inflammation. The hypothesis was that induced normothermia would improve hemodynamics and decrease markers of inflammation. Chapter 7: We used a human endotoxemia model to study the effects of induced normothermia on coagulation and endothelial activation in order to determine if induced normothermia attenuated endotoxemia induced coagulation abnormalities. We hypothesized that induced normothermia would mitigate LPS- induced coagulation abnormalities. Part III: TTM and cardiac arrest Chapter 8: We examined the effects of targeted temperature management on mechanical ventilation in patients after cardiac arrest to determine association with outcome. We hypothesized that treatment with TTM at 33°C was associated with a lower minute volume ventilation compared to TTM at 36°C. Chapter 9: We explored the role that arterial carbon dioxide levels may have in the neurological outcome of cardiac arrest patients, and analyzed the interaction between mild hypercapnia and TTM in relation to neurological outcome.