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Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy")
Marko Fiege1, Frank Wappler, Ralf Weisshorn
1Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. fiege@uke.uni-hamburg.de
Background:
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine.
Methods:
MH-nontriggering general anesthesia was performed in six MH-susceptible (MHS) and six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central venous pH /= 2.0 degrees C. Once MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and hyperventilation with 100% oxygen was initialized.
Results:
Administration of 8 mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed clinical signs of hypermetabolism, but even after administration of 12 mg/kg MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs of MH immediately.
Conclusions:
MDMA induces MH in genetically susceptible swine in relevant doses. Therefore, MHS patients should avoid use of MDMA or related drugs. Patients with a personal or family history of MDMA-induced hyperthermia should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in therapy of MDMA-induced porcine MH.
Insights
3,4-Methylenedioxymethamphetamine (MDMA) triggers malignant hyperthermia (MH) in susceptible swine. Individuals with a history of MH susceptibility should avoid MDMA and related drugs.
Area of Science:
- Anesthesiology
- Toxicology
- Pharmacology
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA) can cause acute toxic effects including hyperthermia.
- Clinical similarities between MDMA intoxication and malignant hyperthermia (MH) suggest a potential link.
- This study investigated MDMA's potential to trigger MH in susceptible individuals.
Purpose of the Study:
- To determine if MDMA triggers malignant hyperthermia (MH) in susceptible swine.
- To assess the dose-dependent effects of MDMA on MH-susceptible and MH-normal swine.
- To evaluate the efficacy of dantrolene in treating MDMA-induced MH.
Main Methods:
- MH-susceptible (MHS) and MH-normal swine were administered escalating doses of MDMA (0.5-12 mg/kg) under general anesthesia.
- MH was clinically defined by specific thresholds for Pco2, pH, and core body temperature.
- Standardized MH treatment (dantrolene, sodium bicarbonate, oxygen) was initiated upon MH occurrence.
Main Results:
- MDMA at 8 mg/kg triggered MH in all MHS swine.
- MH-normal swine exhibited moderate hypermetabolic signs, less severe than MHS swine, even at 12 mg/kg MDMA.
- Dantrolene therapy partially and immediately alleviated clinical signs of MDMA-induced MH in MHS swine.
Conclusions:
- MDMA is a potent trigger of malignant hyperthermia in genetically susceptible swine at relevant doses.
- Individuals with MH susceptibility should strictly avoid MDMA and related substances.
- Testing for MH susceptibility is recommended for patients with a personal or family history of MDMA-induced hyperthermia.
- Dantrolene demonstrates efficacy in managing MDMA-induced porcine MH crises.
