How is hyperthermia treated in MDMA toxicity?

Updated: May 30, 2020
  • Author: In-Hei Hahn, MD, FACEP, FACMT; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
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Answer

Hyperthermia and the risk of serotonin syndrome can result in increased mortality with complications of disseminated intravascular coagulation, rhabdomyolysis, and acute kidney injury. Institute general cooling measures and treat rhabdomyolysis with generous intravenous hydration and alkalinization of the urine. Patients presenting with severe hyperthermia require aggressive cooling measures and adequate fluid resuscitation. Obtain a rectal temperature. Aggressively cool hyperthermic patients, attempting to reduce the core temperature to 101°F within 30-45 minutes.

Morbidity is directly related to the severity and duration of hyperthermia. Management considerations are as follows:

  • Undress the patient
  • Apply evaporative cooling; spray water onto the body and use an electric fan to circulate the air
  • Apply ice packs to the groin and axilla
  • Iced gastric lavage may be considered
  • In extreme cases, ice-bath immersion may be required for the correction of hyperthermia
  • Control shivering with a benzodiazepine
  • Antipyretics are not useful

Dantrolene (1 mg/kg or 80 mg intravenously [IV]) has been used for the treatment of hyperpyrexia after conventional therapy. Dantrolene is typically used to treat malignant hyperthermia, a genetic disorder of the skeletal muscle due to a defect in the ryanodine receptor that allows for massive release of calcium from the sarcoplasmic reticulum during exposures to general anesthetics.

MDMA-induced hyperthermia is thought to be centrally mediated via serotonin toxicity. Although the mechanism of dantrolene does not seem to correlate with what is known about MDMA-induced hyperthermia, dantrolene was first used to treat hyperthermia in the setting of MDMA-related hyperpyrexia in 1992 due to the similarity of presentation.

A systematic compilation of MDMA case reports suggests possible evidence of benefit in using dantrolene to treat hyperthermia. [27] The study showed decreased morbidity and mortality with rare side effects from the dantrolene itself, especially in patients who present with temperatures above 40°C, and particularly above 42°C. The biggest caveat with using case series and case reports is recognizing the limitations of reporting and publication biases.

Monitor hyponatremia as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and excessive water intake for resultant cerebral edema and seizures. In severe cases, administration of 3% saline and furosemide may be indicated to correct the hyponatremia, but at a rate no greater than 0.5-1 mEq/L/h.

A study in an animal model found that clozapine resulted in a marked and immediate reversal of MDMA-induced hyperthermia, via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia, and labetalol was ineffective. [28]


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