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KEY POINTS
Fever should prompt investigation into potential infectious as well as noninfectious etiologies.
Treatment with empiric antibiotics may be indicated in particular in patients with other signs of sepsis such as tachycardia and hypotension.
Fever may also be caused by potentially life-threatening noninfectious syndromes such as thromboembolic disease and it is important to investigate these possibilities as well.
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Fever is a state of elevated core temperature that is often a sign of infection in patients admitted to the intensive care unit (ICU). It should prompt investigation into potential infectious as well as noninfectious etiologies. Treatment with empiric antibiotics may be indicated in particular in patients with other signs of sepsis such as tachycardia and hypotension. Fever may also be caused by potentially life-threatening noninfectious syndromes such as thromboembolic disease and it is important to investigate these possibilities as well.
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The febrile response, of which temperature rise is a component, is a complex physiologic reaction to disease, involving cytokine-mediated rise in core temperature, generation of acute phase reactants, and activation of numerous physiologic, endocrinologic, and immunologic systems. In contrast, simple heat illness or malignant hyperthermia is an unregulated rise in body temperature caused by inability to eliminate heat adequately. Fever begins with the production of one or more proinflammatory cytokines in response to exogenous pyrogens (microorganisms, toxic agents) or immunologic mediators. Interleukin 1 (IL-1), tumor necrosis factor (TNF), lymphotoxin, interferons (IFNs), and interleukin 6 (IL-6) are known and documented to induce fever independently. Cytokines interact with receptors located at the organum vasculosum of the lamina terminalis causing synthesis and release of prostaglandins, chiefly prostaglandin E2, which raises body temperature by initiating local cAMP production, which resets the thermoregulatory set point of the hypothalamus and by coordinating other adaptive responses such as shivering and peripheral vasoconstriction. Fever induces the production of heat shock proteins (HSPs), a class of proteins critical for cellular survival during stress. HSPs may have an anti-inflammatory role and indirectly decrease the level of proinflammatory cytokines. Core body temperature may be influenced by numerous external factors including cooling blankets or continuous venovenous hemofiltration. Patients who have suffered neurologic injury or central nervous system (CNS) hemorrhage may also have hypothalamic dysfunction that could lead to elevated body temperature.
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The incidence of fever in the ICU ranges from 28% to 70%. Infectious as well as noninfectious etiologies contribute almost equally to the causation of febrile episodes. The finding of a new fever in an ICU patient has a significant impact on health care costs due to the blood cultures, radiologic imaging, and antibiotics that are often empirically initiated. It is therefore important to have a good understanding of the mechanisms and etiology of fever in ICU patients, how and when to initiate a diagnostic workup, and when initiation of antibiotics is indicated.