Matt Harmon

206 Chapter ten mitochondrial respirometry has emerged as a technique to continuously measure mitochondrial pO2 and mitochondrial oxygen consumption (mitoVO2). 36 It would be interesting to monitor parameters of cellular hypoxia during temperature alterations in sepsis. Similarly, studying the genomic profile of septic patients using microarray technology can help us comprehend underlying pathophysiologic mechanisms during temperature alterations in sepsis. Intriguingly, there even seems to be an overlap between spontaneous temperature alterations in sepsis, which results in an upregulation of the trypotophan degradation pathway and TTM applied in cardiac arrest, which induces tryptophan catabolism. 37 Although the relationship between these two findings is unclear, these findings indicate that pathways like tryptophan are modifiable and could be used to monitor spontaneous and induced temperature alterations. Taken together, we need a better understanding of the relationship between body temperature and underlying pathophysiologic mechanisms in critically ill patients before new clinical TTM trials are initiated. Although mechanistic studies in cardiac arrest and sepsis may not directly be as rewarding, they will provide a more focused direction to future TTM studies and help us move away from the one-size fits all approach in clinical trials. Conclusion In summary, body temperature and the application of TTM in critically ill patients is decidedly complex. The future will likely warrant a tailored temperature management approach in which we monitor the risk-benefits of a critically ill patient’s body temperature in real-time. This thesis describes several aspects of the spontaneous hypothermic response to sepsis. It also examines the effects of TTM in hyperinflammatory states such as sepsis and cardiac arrest. Although this thesis does not definitively answer fundamental questions on the etiology of the body temperature alterations in the critically ill, it does provide important pieces of our understanding of spontaneous and induced body temperature alterations in critically ill and a foundation to further study these phenomena.