Does dantrolene improve outcomes in ecstasy-induced hyperthermia?

November 2, 2010, 5:46 pm

★★★½☆

Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. Grunau BE et al. CJEM 2010;12:435-42.

Abstract

Although the precise mechanism by which MDMA (ecstasy) causes severe hyperthermia and multi-organ failure in some patients is not known, speculation that this life-threatening syndrome might be similar to malignant hyperthermia has prompted some clinicians to use dantrolene as an antidote.  On the other hand, other authors have pointed out that since dantrolene is constituted as an alkaline solution, increasing urine pH would decrease MDMA clearance and thus could be detrimental.  Since the literature on this question consists entirely of case reports and very small case series, it is not at all clear what effect — if any — dantrolene has in these cases.

The authors, from the University of British Columbia, set out to conduct a systematic review of literature concerning MDMA-associated hyperthermia, and provide descriptive (not analytical) statistics comparing cases receiving dantrolene with those that did not.  They identified 53 eligible articles describing 71 cases.  Twenty-six of these 71 patients received dantrolene.  Although because of the uncontrolled nature of the data the exact numbers aren’t important, the authors found that the patients who received dantrolene had higher rates of survival and severe complications. They conclude that: “Our systematic review suggests that dantrolene is safe for patients with MDMA-related hyperpyrexia.  Dantrolene may also be associated with improved survival and reduced complications . . .”

I gave this article 3-1/2 skulls because it addresses an interesting question, and the authors are quite clear in discussing the limitations of the underlying data.  For one thing, there is potential publication bias, since cases of MDMA-associated hyperthermia that do well with standard treatment — or do poorly despite receiving dantrolene — may be under-reported.  There is also an additional potential bias that they don’t discuss — the inability to account for confounding factors. For example, when these severely hyperthermic patients arrive in emergency department, the treating team is busy with standard resuscitation — ABCs, cooling measures, etc.  The sicker patients may die during this initial phase.  Those who are less ill are more likely to survive initial stabilization, at which time there would be opportunity to contact a poison information center and consider other specific treatment possibilities such as dantrolene.  Therefore, patients who live long enough to receive dantrolene may be a group already selected to have a better outcome.  The case report data can not account for this.

The same issue of Canadian Journal of Emergency Medicine also has an additional report describing a case of MDMA-associated hyperthermia treated with dantrolene.

Related post: San Francisco rave fatality: tainted drugs?

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