Matt Harmon

10 Chapter one Body temperature alterations in critically ill patients Body temperature alterations are common in critically ill patients in the intensive care unit (ICU). In a study examining body temperature alterations on the ICU, 9% of patients presented with or developed hypothermia and 28% fever during their ICU admission. 1 These body temperature alterations can occur spontaneously as a result of underlying pathologic processes, or they may be clinically induced as part of a patient’s treatment. Spontaneous body temperature alterations are associated with a range of different pathologic conditions in the intensive care. Sepsis is the most common cause of both fever and hypothermia. Fever may also occur after brain injury, i.e. after traumatic brain injury or hypoxic-ischemic brain injury post cardiac arrest. Less common causes of fever in the ICU include endocrine- or drug-induced fever. 2 Besides spontaneous hypothermia in sepsis, a number of other factors can cause hypothermia requiring ICU admission, including cold exposure, endocrine abnormalities and drug overdoses. 1,3 Induced temperature alterations or targeted temperature management (TTM), in which body temperature is physically or pharmacologically altered, is used to treat several pathologic conditions in the ICU. TTM includes normalizing body temperature, for example actively cooling patients to normothermia with traumatic brain injury or rewarming patients with spontaneous hypothermia in sepsis. But it can also imply actively inducing a non-normothermic body temperature. In hypoxic-ischemic brain injury after cardiac arrest, fever is neurologically detrimental 4 and TTM in which patients are cooled to 32°C-36°C, is now a cornerstone in mitigating brain injury. 5 In sepsis, both induced normothermia and induced hypothermia are being explored as experimental clinical therapies. 6,7 The chapters presented in this thesis are introduced in the following paragraphs. Spontaneous temperature alterations in sepsis Fever: the pathophysiology of a febrile response Normal body temperatures in healthy individuals range from 35.6°C to 37.7°C and fluctuate over the course of a day. 8 An elevated body temperature is commonly termed fever or pyrexia. The term hyperthermia is also used but denotes a pathologic increase in body temperature that is not related to an altered hypothalamic set point. 9 Fever is a highly conserved, phylogenetic response induced by both infectious and noninfectious causes. 10 During an infection, fever is elicited by pathogen associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS),