Chapter 017. Fever and Hyperthermia (Part 2) Hyperthermia Although most patients with elevated body temperature have fever, there are circumstances in which elevated temperature represents not fever but hyperthermia (Table 17-1). Hyperthermia is characterized by an uncontrolled increase in body temperature that exceeds the body's ability to lose heat. The setting of the hypothalamic thermoregulatory center is unchanged. In contrast to fever in infections, hyperthermia does not involve pyrogenic molecules (see "Pyrogens," below). Exogenous heat exposure and endogenous heat production are two mechanisms by which hyperthermia can result in dangerously high internal temperatures. Excessive heat production can easily cause hyperthermia despite physiologic and behavioral control of body temperature. For example, work or exercise in hot environments can produce heat faster than peripheral mechanisms can lose it. Table 17-1 Causes of Hyperthermia Syndromes Heat Stroke Exertional: Exercise in higher-than-normal heat and/or humidity Nonexertional: Anticholinergics, including antihistamines; antiparkinsonian drugs; diuretics; phenothiazines Drug-Induced Hyperthermia Amphetamines, cocaine, phencyclidine (PCP), methylenedioxymethamphetamine (MDMA; "ecstasy"), lysergic acid diethylamide (LSD), salicylates, lithium, anticholinergics, sympathomimetics Neuroleptic Malignant Syndrome Phenothiazines; butyrophenones, including haloperidol and bromperidol; fluoxetine; loxapine; tricyclic dibenzodiazepines; metoclopramide; domperidone; thiothixene; molindone; withdrawal of dopaminergic agents Serotonin Syndrome Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants Malignant Hyperthermia Inhalational anesthetics, succinylcholine Endocrinopathy Thyrotoxicosis, pheochromocytoma Central Nervous System Damage Cerebral hemorrhage, status epilepticus, hypothalamic injury Source: After FJ Curley, RS Irwin, JM Rippe et al (eds): Intensive Care Medicine, 3d ed. Boston, Little, Brown, 1996.Heat stroke in association with a warm environment may be categorized as exertional or nonexertional. Exertional heat stroke typically occurs in individuals exercising at elevated ambient temperatures and/or humidities. In a dry environment and at maximal efficiency, sweating can dissipate ~600 kcal/h, requiring the production of >1 L of sweat. Even in healthy individuals, dehydration or the use of common medications (e.g., over-the-counter antihistamines with anticholinergic side effects) may precipitate exertional heat stroke. Nonexertionalheat stroke typically occurs in either very young or elderly individuals, particularly during heat waves. According to the Centers for Disease Control and Prevention, there were 7000 deaths attributed to heat injury in the United States from 1979 to 1997. The elderly, the bedridden, persons taking anticholinergic or antiparkinsonian drugs or diuretics, and individuals confined to poorly ventilated and non-air-conditioned environments are most susceptible.Drug-induced hyperthermia has become increasingly common as a result of the increased use of prescription psychotropic drugs and illicit drugs. Drug-induced hyperthermia may be caused by monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, and amphetamines and by the illicit use of phencyclidine (PCP), lysergic acid diethylamide (LSD), methylenedioxymethamphetamine (MDMA, "ecstasy"), or cocaine.Malignant hyperthermia occurs in individuals with an inherited abnormality of skeletal- muscle sarcoplasmic reticulum that causes a rapid increase in intracellular calcium levels in response to halothane and other inhalational anesthetics or to succinylcholine. Elevated temperature, increased muscle metabolism, muscle rigidity, rhabdomyolysis, acidosis, and cardiovascular instability develop within minutes. This rare condition is often fatal. The neuroleptic malignant syndrome occurs in the setting of neuroleptic agent use (antipsychotic phenothiazines, haloperidol, prochlorperazine, metoclopramide) or the withdrawal of dopaminergic drugs and is characterized by "lead-pipe" muscle rigidity, extrapyramidal side effects, autonomic dysregulation, and hyperthermia. This disorder appears to be caused by the inhibition of central dopamine receptors in the hypothalamus, which results in increased heat generation and decreased heat dissipation. The serotonin syndrome, seen with selective serotonin uptake inhibitors (SSRIs), MAOIs, and other serotonergic medications, has many overlapping features, including hyperthermia, but may be distinguished by the presence of diarrhea, tremor, and myoclonus rather than the lead-pipe rigidity of the neuroleptic malignant syndrome. Thyrotoxicosis and pheochromocytoma can also cause increased thermogenesis. It is important to distinguish between fever and hyperthermia since hyperthermia can be rapidly fatal and characteristically does not respond to antipyretics. In an emergency situation, however, making this distinction can be difficult. For example, in systemic sepsis, fever (hyperpyrexia) can be rapid in onset, and temperatures can exceed 40.5°C. Hyperthermia is often diagnosed on the basis of the events immediately preceding the elevation of core temperature— e.g., heat exposure or treatment with drugs that interfere with thermoregulation. In patients with heat stroke syndromes and in those taking drugs that block sweating, the skin is hot but dry, whereas in fever the skin can be cold as a consequence of vasoconstriction. Antipyretics do not reduce the elevated temperature in hyperthermia, whereas in fever—and even in hyperpyrexia—adequate doses of either aspirin or acetaminophen usually result in some decrease in body temperature. . Chapter 017. Fever and Hyperthermia (Part 2) Hyperthermia Although most patients with elevated body temperature have fever, there are circumstances in. increased thermogenesis. It is important to distinguish between fever and hyperthermia since hyperthermia can be rapidly fatal and characteristically does not respond to antipyretics. In an. prescription psychotropic drugs and illicit drugs. Drug-induced hyperthermia may be caused by monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, and amphetamines and by the illicit use