Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review

Abstract

Objective: The use of dantrolene in the treatment of hyperpyrexia related to MDMA (3,4-methylenedioxymethamphetamine) is controversial, with little data available to guide clinical decision-making. Although the treatment is recommended by several poison control centres, published data are primarily in the form of case reports and animal and in vitro experiments. We conducted a systematic review to investigate the published evidence regarding the safety and benefits of dantrolene for MDMA-related hyperpyrexia in humans. Data sources: A systematic search of Embase and MEDLINE was conducted from the earliest possible date to November 2008. Study selection: All human trials and case reports of MDMArelated hyperpyrexia were considered. Data extraction: Data were abstracted systematically and characteristics including use of dantrolene, adverse reactions attributed to dantrolene, peak temperature, complications from MDMA-related hyperpyrexia and survival were recorded. Data synthesis: Our search yielded 668 articles of which 53, reporting 71 cases of MDMA-induced hyperpyrexia, met our inclusion criteria. No clinical trials, randomized controlled trials, observational studies or meta-analyses were identified. Dantrolene was used in 26 cases. Patient characteristics were similar in the dantrolene and no dantrolene groups. The proportion of survivors was higher in the dantrolene group (21/26) than in the no dantrolene group (25/45). This difference was especially pronounced in those with extreme (≥ 42°C) and severe (≥ 40°C) fever, with a survival rate of 8 of 13 and 10 of 10, respectively, in the dantrolene group compared with 0 of 4 and 15 of 27 in the no dantrolene group. There were no reports of adverse events attributable to dantrolene with the exception of a possible association with an episode of transient hypoglycemia. Conclusion: 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, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia, although this conclusion must be interpreted with caution given the risk of reporting or publication bias.

Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study

“…Among the few pharmacological options available dantrolene a drug used in the treatment of MH may be beneficial in several hyperthermic conditions [10]- [13]. The common mechanism underlying rationale for use of dantrolene is the dysregulation of calcium as the major component of skeletal muscle generated heat in different hyperthermic conditions.…”

Dantrolene treatment in a patient with uncontrolled hyperthemia after general anesthesia: a case report of suspected malignant hyperthermia - A case report -

“…It has been noted that dantrolene may be effective in treating hyperthermia from many causes unrelated to MH caused by anesthesia [12]. On the basis of the similarity between a variety of drug-induced hyperthermic syndromes and MH, dantrolene has been used to effectively treat several syndromes, such as the neuroleptic malignant syndrome, 3,4-methylenedioxy-methamphetamine toxicity, and hyperthermia related to the new onset of juvenile diabetes in adolescents [13][14][15]. …”

Ecstacy‐induced delayed rhabdomyolysis and neuroleptic malignant syndrome in a patient with a novel variant in the ryanodine receptor type 1 gene

“…There are no randomised controlled trials that provide definitive evidence for the role of dantrolene in managing hyperpyrexia induced by MDMA or neuroleptic malignant syndrome. Grunau et al [24] found improved survival rates with dantrolene therapy (81% vs 56%) in patients with hyperpyrexia induced by MDMA, but their systematic review included only case reports and case series. In our case, dantrolene appeared effective in reducing both CK levels and hyperthermia (Fig.…”