Aspirin reduces fever but does not lower body temperature in a patient with heat stroke. What explains this difference?

• A Aspirin blocks prostaglandin E2 synthesis only when the set-point is pathologically elevated
• B Aspirin acts peripherally on sweat glands, which fail in heat stroke
• C Heat stroke raises the hypothalamic set-point, which aspirin cannot reset ✓
• D Aspirin is ineffective at core temperatures above 40 degrees C

Explanation

Fever results from exogenous pyrogens inducing cytokines that raise the hypothalamic set-point via PGE2, so cyclooxygenase inhibition by aspirin restores the set-point toward normal. Heat stroke is passive hyperthermia where heat load overwhelms dissipation mechanisms while the set-point remains normal at 37 degrees B, so there is no elevated set-point for an antipyretic to lower. Active external cooling is required instead.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.