Matt Harmon

204 Chapter ten interventions that require optimization and standardization in order to maximize TTMs neuroprotective effects. 29 The studies presented in this thesis aid in the optimization and standardization of TTM and ultimately could lead to TTM treatment that is adapted towards specific patient characteristics and needs. A future outlook on the appropriate body temperature in cardiac arrest and sepsis; moving away from a one size fits all approach. There likely is an optimum body temperature, or body temperature range, for individual patients in specific disease states. Studies to date have given us a general idea of what acceptable temperature ranges are for patients, depending on their underlying illness. However, any further progress in identifying the optimal body temperature and TTM strategy for patients in cardiac arrest and sepsis risks a multitude of large, expensive and likley negative clinical trials. To advance TTM research in cardiac arrest and sepsis we need new biomarkers, in order to better understand underlying pathophysiologic processes in critically ill patients and their relationship to body temperature. Using these biomarkers, we could potentially individualize temperature management and improve clinical outcomes. In cardiac arrest, there is evidence that the optimum body temperature is likely patient dependent. Results from the HYPERION trial showed that in cardiac arrest patients with non-shockable rhythms, TTM to 33°C led to a higher percentage of patients who survived with a favorable neurologic outcome as compared to 37°C. 30 The results from the HYPERION trial indicate that the necessary depth of TTM in patients may be dependent on the extent of neurologic damage as patients with non-shockable rhythms have significantly worse cardiac arrest characteristics including longer low-flow states. Unfortunately, TTM is currently a one-size fits all treatment and the chosen target temperature is usually based on a physician’s preference or local protocol. 31 This approach diminishes the underlying complexities of brain injury after cardiac arrest. In cardiac arrest, monitoring tools are needed to assess and monitor the appropriate depth and duration of TTM treatment in individual patients. Continuous electroencephalography (EEG) monitoring is being validated as a prognostication tool to predict clinical outcome after cardiac arrest. 32 In a recent study, cardiac arrest patients with cerebral edema or a malignant EEG fared better at lower target temperatures. 33 These results indicate that EEG monitoring could be used to determine the necessary depth and duration of TTM treatment. Studies should also focus on identifying brain injury specific biomarkers such as serum Tau protein levels. The use of these tools should not be limited to pre-TTM brain injury stratification and treatment allocation. Using these tools