Matt Harmon

15 Chapter one for activating aerobic heat production while the capacity for aerobic metabolism is not yet compromised. 28 In general, old age is commonly associated with body temperature alterations. 41 Elderly have reduced sweat gland output, altered cutaneous vasomotor control and decreased cardiac output limiting their ability to regulate heat. 42 However, several studies reported no significant difference in age when comparing hypothermic patients to nonhypothermic patients. 24,26,35 Taken together, the mechanisms underlying the hypothermic response in sepsis are not understood. Further understanding of the hypothermic response is crucial for optimal treatment of these patients and warrants further investigation. Induced body temperature alterations Manipulation of body temperature in sepsis TTM in sepsis encompasses both the practice of actively cooling septic patients, as well as rewarming hypothermic septic patients. These practices are a result of clinical observations on the relationship between body temperature and mortality. Figure 2 shows the odds of mortality for septic patients at different peak body temperatures in the first 24 hours of ICU admission, adjusted for disease severity. These observations suggest that both high grade fever (temperatures > 40°C) as well as hypothermia may be detrimental to patients. In clinical practice, to counteract fever in sepsis, body temperature may pharmacologically or physically lowered, or in the case of hypothermia body temperature is physically increased. 43 However, whether manipulation of body temperature is beneficial in sepsis, is not known. Induced normothermia and induced hypothermia in sepsis During sepsis, fever could be driving the cellular metabolic deficit and cytotoxicity due to enhanced immune effectors discussed above. 22 Actively cooling septic patients with fever to normothermic or hypothermic temperatures are experimental therapies aimed at limiting the hyperinflammatory response in sepsis and lowering metabolism. Patients with sepsis and fever can be physically cooled to normothermia, termed induced normothermia or fever control. Patients with sepsis and fever can also be cooled to hypothermic temperatures, termed induced hypothermia (or therapeutic hypothermia). Applying induced normothermia and induced hypothermia is controversial in sepsis, for the most part due to the perceived benefits of fever in sepsis which could potentially be negated by cooling. 13 However, preclinical studies in animals have shown that induced hypothermia may improve outcome in sepsis. In a rat