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Think Beyond Infections for Causes of Fever

Fadial, Tom MD

doi: 10.1097/01.EEM.0000651024.58711.6d
    fever. Algorithm for Evaluating Hyperthermia

    A young man with unknown medical history was brought in by ambulance for altered mental status. EMS reported that the patient was agitated, requiring restraints during transport.

    The patient was uncooperative and unable to provide history when he arrived in the ED. His vital signs were notable for tachycardia, tachypnea, and hypertension. A physical examination showed diaphoresis and mydriasis, as well as increased muscle tone, particularly in the lower extremities with ankle clonus. A core temperature was obtained and noted to be elevated at 41.5°C. Point-of-care glucose was normal.

    Rapid external cooling measures were instituted, and several doses of intravenous benzodiazepine were administered, which improved his agitation. Laboratory studies were notable for a modest leukocytosis (a WBC count of 18.4 bil/L without immature forms), serum sodium was 135 mEq/L without an osmolality gap, creatine kinase was slightly elevated without renal dysfunction, and thyroid function tests were normal. A toxicology screen was negative, an ECG revealed sinus tachycardia but was otherwise normal, and noncontrast CT of the head was also normal.

    After a brief admission in the intensive care unit, the patient's mental status improved, and he reported MDMA use on the evening of his presentation. He also described a history of major depression and said he was taking paroxetine.

    Implicated Agents in Drug-Induced Hyperthermic Syndromes: Serotonin Syndrome

    Evaluating Elevated Temperature

    The designation of 38°C as suspicious for fever dates to 1868 and the analysis of more than one million (axillary) temperature measurements by Carl Wunderlich. (Das Verhalten Der Eigenwärme in Krankheiten. 1870. Any cutoff is arbitrary and requires recognition of the clinical context and normal daily variations (with nadir in the morning and peak in the evening). (JAMA. 1992;268[12]:1578; Compr Ther. 1995;21[12]:697.) What is clear is that peripheral thermometry (unless demonstrating fever) is unreliable, and a core temperature should be sought. (Ann Intern Med. 2015;163[10]:768.)


    Temperature homeostasis is a balance between heat production and dissipation maintained by the anterior hypothalamus. Heat production is a byproduct of normal metabolic processes and skeletal muscle activity. Conservation, maintenance, or dissipation of heat is aided by cutaneous vasodilation, sweating, or behavioral responses.

    Fever is caused by endogenous or exogenous pyrogens, which alter the homeostatic set-point, inducing thermogenesis and elevating body temperature. Precipitants of fever are usually infectious, but noninfectious processes (e.g., malignancy, tissue ischemia or infarction, and autoimmune disease) resulting in inflammation can provoke a similar response. (J Endotoxin Res. 2004;10[4]:201; Curr Opin Infect Dis. 2002;15[3]:241; Infect Dis Clin North Am. 1996;10[2]:433;

    There is no explicit temperature distinction to diagnose hyperthermia. Instead, the physiologic mechanism is different. The body's homeostatic mechanisms in hyperthermia are dysfunctional or overwhelmed due to heat exposure, excess production, ineffective dissipation, or hypothalamic malfunction.

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    Dr. Fadialis an assistant professor of emergency medicine at McGovern Medical School in Houston. As the educational technology and innovation officer there, he develops unique educational tools, including algorithms that can be found at His other medical education projects can be found at

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