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Question:

A 45-year-old woman is brought to the hospital after she collapsed during an airshow on a hot summer day.  The patient has a history of fibromyalgia and takes amitriptyline.  Temperature is 40.5 C (104.9 F), blood pressure is 90/60 mm Hg, pulse is 110/min, and respirations are 22/min.  The skin is warm and red.  She is disoriented.  Neurologic examination shows no focal findings.  If this patient's medication contributed to her current condition, which of the following mechanisms is most likely responsible?

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Explanation:

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This patient developed severe hyperthermia and encephalopathy while spending time outside on a hot summer day.  This presentation is suggestive of nonexertional heat stroke (NHS), a life-threatening multisystem disorder characterized by hyperthermia (typically >40 C [104 F]) associated with CNS dysfunction (eg, encephalopathy, syncope).  Other classic manifestations of heat stroke include tachycardia, tachypnea, hypotension, flushing, and end-organ dysfunction (eg, pulmonary edema, renal/hepatic failure).  Diaphoresis may or may not be present on examination, depending on hydration status and sweat gland function.

The body normally maintains a core temperature of ~37 C (98.6 F) through multiple thermoregulatory mechanisms controlled by the anterior hypothalamus; excessive temperature stimulates diaphoresis, peripheral vasodilation, and behavioral changes (eg, seeking shade).  However, certain medications can interfere with these processes, thereby promoting hyperthermia.  These medications include the following:

  • Anticholinergics (eg, amitriptyline, scopolamine) inhibit diaphoresis, limiting the body's primary mechanism of heat dissipation.

  • Sympathomimetics (eg, amphetamines, cocaine) impair peripheral vasodilation, limiting heat transfer to the skin (Choice E).

  • Dopaminergic antagonists (eg, chlorpromazine, haloperidol) disrupt hypothalamic thermoregulation, likely by blocking dopamine transmission in the hypothalamus (Choice C).

  • Diuretics (eg, furosemide) and beta blockers (eg, metoprolol) limit the cardiac response to heat stress by reducing blood volume or heart rate, thereby decreasing blood flow to the skin (Choice A).

(Choice D)  Malignant hyperthermia is a rare autosomal dominant disorder that occurs due to uncontrolled efflux of calcium from the sarcoplasmic reticulum, resulting in increasing muscle tone (eg, myoclonus, rigidity) and hyperthermia.  However, it typically occurs after administration of certain anesthetics (eg, halothane, succinylcholine), not tricyclic antidepressants.

Educational objective:
Nonexertional heat stroke (NHS) is a life-threatening disorder characterized by hyperthermia (typically >40 C [104 F]) associated with CNS dysfunction (eg, encephalopathy, syncope).  Anticholinergic medications promote heat stroke by impairing diaphoresis.  Other medications associated with NHS include sympathomimetics, dopamine antagonists, diuretics, and beta blockers.