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Three Part Question

In [patients who abuse Ecstasy], would [the use of Dantrolene] have a role in [the treatment of the drug induced hyperthermia].

Clinical Scenario

A 21-year-old male presents to the emergency department after taking few Ecstasy tablets on a night out. He is agitated, sweaty with a body temperature of 42.5°C. Reduction of the hyperthermia is initiated by stripping the patient, applying cold packs, and later using cold IV fluids and Paracetamol.
Would the use of Dantrolene be of any benefit in the management of this case.

Search Strategy

Pubmed.
Medline (R) 1950 to February week 4, 2008 using the OVID interface.
LIMIT to human AND English language.
{exp DANTROLENE/ or dantrolene.mp} AND {exp Amphetamine/ or amphetamine.mp OR exp MDMA OR exp Speed/ speed.mp OR exp Ecstasy/ ecstasy.mp} AND {exp Hyperthermia/ or hyperthermia}

Search Outcome

19 papers but only one was relevant to our search.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Hall et al 2006 UK		Review.	Peak temperatures in the range of 40-40.9°C.	6/6 survivors with Dantrolene use and 4/5 without.	Not a randomised controlled, blinded, or pilot study.
			Peak temperatures in the range of 41-41.9°C.	4/4 survivors with Dantrolene use and 2/5 without.

Comment(s)

Dantrolene is a muscle relaxant that inhibits the release of calcium from sarcoplasmic reticulum by binding to ryanodine receptor (RyR) channel. It's clinical benefit has been proven in the treatment of Malignant Hyperthermia that results from the use of antipsychotic and anaesthetic drugs. A rare disorder, Malignant Hyperthermia is characterised by an hereditary impairement of the sarcoplasmic reticulum to sequester calcium which subsequently leads to severe muscular tone and contractions, and later to a considerable high body temperatures. Ecstasy, or 3,4-methylenedioxymethamphetamine (MDMA), produces a fairly similar hyperthermia. It mediates an increase in the extracellular concentration of serotonin by blocking the serotonin transporter (SERT) which has the effect of increasing muscular tone and contractions, and thus body temperature. Many cases of Dantrolene use with Ecstasy or Amphetamine induced hyperthermia had been reported. Outcomes showed a better survival rate and more rapid temperature control when Dantrolene was concomittently used, but did not alter the clinical course when peak body temperature exceeded 42°C, although one case had a survival with a body temperature of 42.9°C.

Clinical Bottom Line

Dantrolene use in Ecstasy induced hyperthermia might have a role in improving the survival outcome when peak body temperature ranges between 40 and 41.9°C. Level of evidence Level 4 - only case series and a review are so far available. Further studies are required to establish a definite evidence base for the use of Dantrolene in such cases.

References

1. Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. British Journal of Anaesthesia. 2006;96(6):678-85.