3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia

Background 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. Objective 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. Design Experimental study, using an animal model of Pietrain pigs. Settings Institute for Research in Operative Medicine, University of Witten/Herdecke, 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 Pietrain pigs, and cumulative doses of MDMA were administered to each animal. Interventions 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. Main outcome measures 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. Results MDMA administration led to fulminant hypermetabolic and hyperthermic responses in malignant hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant decreases inpH(susceptible: pH7.21 +/- 0.11, normal: pH 7.21 +/- 0.07), severe hypercapnia (susceptible: p(a)CO(2) 10.3 +/- 3.5 kPa, normal: p(a)CO(2) 9.8 +/- 1.7 kPa), and hyperthermia (susceptible: 40.6 +/- 2.08 degrees C, normal: 40.1 +/- 0.48 degrees C). Therewere 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. Conclusion 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 hyperthermianormal pigs, with life-threatening malignant hyperthermia-like symptoms which are responsive to supportive treatment and dantrolene sodium suspension. Eur J Anaesthesiol 2013; 30:29-37