Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy").
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 </= 7.20, and increase of body core temperature >/= 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.
Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. fiege@uke.uni-hamburg.de
Marko
M
Fiege
Frank
F
Wappler
Ralf
R
Weisshorn
Mark U
MU
Gerbershagen
Melanie
M
Menge
Jochen
J
Schulte Am Esch
D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003620:Dantrolene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008305:Malignant Hyperthermia / Q000188:drug therapy / Q000503:physiopathology*; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013552:Swine
D006213:Hallucinogens; D009125:Muscle Relaxants, Central; D002245:Carbon Dioxide; D003620:Dantrolene; D018817:N-Methyl-3,4-methylenedioxyamphetamine