Rationale:

• In contrast to fever, in which the hypothalamic (central) set point is elevated, no such changes exist in hyperthermic syndromes in general or in heatstroke in particular.
• The elevated body temperature in heatstroke stems from the imbalance between heat production and heat dissipation; therefore, antipyretic agents that affect the hypothalamic (central) temperature set point are irrelevant, and moreover, the possible hepatocellular damage of these agents might be harmful, especially when taking into consideration heat-induced hepatocellular necrosis.
• Dantrolene, a sarcoplasmic calcium release inhibitor, is an effective drug in treating malignant hyperthermia. It was assumed that excess brain calcium release is involved in the pathogenesis of heatstroke, and thus, inhibition of calcium release by dantrolene may be a potential treatment in heatstroke. Experiments have shown that this was not the case because there is probably no involvement of calcium channels in the pathogenesis; therefore, dantrolene is not used to treat heatstroke.
• Heatstroke results in multi-organ failure, the clinical manifestation and treatment of which do not differ among patients with heatstroke.

Evidence:

• Accumulated data do not support the routine use of dantrolene in heatstroke (27; 28).
• Another review article showed that no drug is effective in reducing body temperature in heatstroke. Effective treatment with antipyretics cannot be expected because there is no resetting of the thermoregulatory center (8).
• The damaged liver is vulnerable to acetaminophen hepatotoxicity (4).
• Glucocorticoids have been found to be ineffective in treating heatstroke in animal models (29).

Comments:

• Glutamine and other oral medications are being investigated for their potential to blunt heatstroke (30).