- Author
-
M.B.A. Harmon
- Title
- Exploring body temperature alterations in the critically ill
- Supervisors
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N.P. Juffermans
M.J. Schultz - Co-supervisors
-
J. Horn
- Award date
- 30 April 2021
- Number of pages
- 223
- ISBN
- 9789464164954
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
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. - Persistent Identifier
- https://hdl.handle.net/11245.1/ad95847d-6300-4e75-b307-ad7c741b50e7
- Downloads
-
Thesis
Front matter
Chapter 1: General introduction and outline of this thesis
Chapter 2: Opinions and management of hypothermic sepsis: Results from an online survey
Chapter 3: Risk factors, host response and outcome of hypothermic sepsis
Chapter 4: Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis
Chapter 5: Physiologic and host immune effects of induced normothermia in human endotoxemia
Chapter 6: Induced normothermia ameliorates the procoagulant host response in human endotoxemia
Chapter 7: Practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management: A substudy of the targeted temperature management trial
Chapter 8: Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: An exploratory Target Temperature Management trial substudy
Chapter 9: Microbiological profile of nosocomial infections following cardiac arrest: Insights from the targeted temperature management (TTM) trial
Chapter 10: Summary and general discussion
Chapter 11: Nederlandse samenvatting
List of publications; Curriculum vitae; PhD portfolio; Acknowledgements
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