Exploring body temperature alterations in the critically ill

Body temperature alterations in the critically ill are common but poorly understood. This thesis describes several aspects of the spontaneous hypothermic response to sepsis. It also examines the effects of targeted temperature management (TTM) in hyperinflammatory states such as sepsis and cardiac arrest.
In part I of this thesis we studied potential mechanisms of spontaneous hypothermia in sepsis. We identified low BMI, chronic cardiovascular insufficiency as risk factors for developing hypothermia during sepsis. We also identified signals that hypothermic patients may suffer from increased endothelial dysfunction. In an exploratory microarray analysis, we identified genomic pathways that were upregulated compared to febrile patients with sepsis. Importantly, one of these pathways, tryptophan degradation X, has the potential to lower body temperature, through serotonin mediated pathways.
In part II of this thesis we studied TTM as an experimental treatment for sepsis. In a human volunteer endotoxemia model we found that TTM reduced Disseminated intravascular coagulation (DIC) and plasma Von Willebrand factor levels possibly indicating decreased endothelial activation. Induced normothermia did not affect plasma cytokine levels.
In part III of this thesis we studied TTM treatment in cardiac arrest patients, which is the main treatment modality post-cardiac arrest. However, it can still be improved, to tailor the treatment to the specific needs of cardiac arrest patients. Towards this goal, we studied mechanical ventilation, CO2 levels and infectious complications in patients following cardiac arrest. These studies should aid in the optimization and standardization of TTM treatment in patients with cardiac arrest.