Matt Harmon

17 Chapter one normothermia (target temperatures in these studies were 36.5°C - 38°C and 36.0°C - 37.5°C respectively). 47,48 Comparing the results from these clinical studies is difficult, due to different temperatures management strategies and, in one case, lack of a control group. 6,47,48 The results from these trials warrants further research on the effects and side effects of induced normothermia in sepsis. Induced normothermia is a cheap treatment modality that is easily applicable in ICUs and could potentially benefit septic patients, but needs to be better understood before clinical application in patients. Rewarming of spontaneous hypothermia in sepsis TTM in sepsis also encompasses the rewarming of hypothermic septic patients to normothermia. Rewarming spontaneous hypothermic septic patients is likely a common clinical practice, possibly in an attempt to reverse the perceived negative effects of hypothermia. 26,28 However, it is not known whether rewarming improves outcome. Also, there are limited data on the extent and specifics of rewarming practices nor are there clinical studies on the optimal rewarming strategy in hypothermic sepsis. This is important as rewarming can also be harmful; in cardiac arrest rewarming after treatment with therapeutic hypothermia induces iL-6 and complement activation as well other as markers of ischemia reperfusion. 49 Rewarming rates of > 0.5°C can even adversely affect neurologic outcome. 50 If the spontaneous hypothermic response in sepsis is indeed an adaptive response, the practice of rewarming could ultimately turn out to be unnecessary or even harmful. 28 TTM in cardiac arrest TTM in which body temperature is actively maintained at 32-36°C for 24 hours after cardiac arrest has become the main treatment modality for mitigating hypoxic-ischemic brain injury after cardiac arrest. 5 TTM may decrease the severity of brain dysfunction after cardiac arrest through several mechanisms; by reducing cerebral metabolism, decreasing ischemic reperfusion injury and preventing subsequent cellular apoptosis. 51 TTM may also decrease the production of free radicals 52 and stabilize disruption of the blood-brain barrier, preventing edema. 51 Initially, patients post-cardiac arrest were cooled to 33°C following the results of two clinical trials. 53,54 In 2013 the TTM-trial showed that patients who were cooled to 36°C compared to 33°C had similar mortality rates and neurologic outcome. 55 As a result, current guidelines recommend that patients body temperature be maintained anywhere between 32°C and 36°C for 24 hours. 56 The TTM-trial provides a unique opportunity to study physiology during TTM as well as assess the effects of cooling to two different target temperatures.