3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia.
Clinical symptoms of acute 3,4-methylenedioxymethamphetamine (MDMA) intoxication and malignant hyperthermia have many similarities. At present, however, there is contradictory evidence concerning the malignant hyperthermia trigger potency of MDMA. This study was designed to investigate whether MDMA has malignant hyperthermia trigger potential and leads to malignant hyperthermia in pigs with or without a genetic predisposition to the condition. In addition, the therapeutic effectiveness of a new dantrolene sodium suspension was examined. Experimental study, using an animal model of Piétrain pigs. Institute for Research in Operative Medicine, University of WittenHerdecke, Hospital Cologne Merheim, Cologne, Germany, October 2006 to February 2007. Trigger-free anaesthesia was performed on seven malignant hyperthermia-susceptible and six malignant hyperthermia-normal Piétrain pigs, and cumulative doses of MDMA were administered to each animal. After achieving predefined malignant hyperthermia criteria, standardised therapy was initiated dantrolene sodium suspension (5 mg kg(-1)) was administered and the injection was repeated after 24 min. The malignant hyperthermia trigger potency of MDMA was analysed by monitoring pH, PaCO2 and temperature. In addition, concentrations of thyroid hormone, mitochondrial uncoupling protein 3, noradrenaline and free fatty acids during administration of MDMA and dantrolene sodium suspension were analysed. MDMA administration led to fulminant hypermetabolic and hyperthermic responses in malignant hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant decreases in pH (susceptible pH 7.21 ± 0.11, normal pH 7.21 ± 0.07), severe hypercapnia (susceptible paCO2 10.3 ± 3.5 kPa, normal paCO2 9.8 ± 1.7 kPa), and hyperthermia (susceptible 40.6 ± 2.0°C, normal 40.1 ± 0.4°C). There were no significant differences in changes in clinical and laboratory variables between groups. The dantrolene therapy regimen was effective in treating the MDMA-induced metabolic crises. MDMA is not a classic trigger for the development of malignant hyperthermia reactions in pigs. MDMA intoxication leads to severe, long-lasting hyperthermia and hypermetabolism in both malignant hyperthermia-susceptible and hyperthermia-normal pigs, with life-threatening malignant hyperthermia-like symptoms which are responsive to supportive treatment and dantrolene sodium suspension.