Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy")

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...

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Published in:Anesthesiology (Philadelphia) 2003-11, Vol.99 (5), p.1132-1136
Main Authors: Fiege, Marko, Wappler, Frank, Weisshorn, Ralf, Gerbershagen, Mark U, Menge, Melanie, Schulte Am Esch, Jochen
Format: Article
Language:English
Subjects:
Animals
Blood Gas Analysis
Body Temperature - drug effects
Carbon Dioxide - blood
Dantrolene - pharmacology
Dose-Response Relationship, Drug
Female
Hallucinogens - antagonists & inhibitors
Hallucinogens - toxicity
Heart Rate - drug effects
Hemodynamics - drug effects
Hydrogen-Ion Concentration
Malignant Hyperthermia - drug therapy
Malignant Hyperthermia - physiopathology
Muscle Relaxants, Central - pharmacology
N-Methyl-3,4-methylenedioxyamphetamine - antagonists & inhibitors
N-Methyl-3,4-methylenedioxyamphetamine - toxicity
Swine
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Summary: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. 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. 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. 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.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-200311000-00020