title: 3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia.
abstract: 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.
  
  
  METHODS
  Experimental study, using an animal model of Piétrain pigs.
  
  
  METHODS
  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 Piétrain pigs, and cumulative doses of MDMA were administered to each animal.
  
  
  METHODS
  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.
  
  
  METHODS
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Hospital Cologne Merheim, University of Witten/Herdecke, Cologne, Germany. schuettej@kliniken-koeln.de
authors.forename: Jan K
authors.initials: JK
authors.lastname: Schütte
authors.forename: Ute
authors.initials: U
authors.lastname: Schäfer
authors.forename: Sandra
authors.initials: S
authors.lastname: Becker
authors.forename: Christiane
authors.initials: C
authors.lastname: Oldewurtel
authors.forename: Alexander
authors.initials: A
authors.lastname: Starosse
authors.forename: Peter
authors.initials: P
authors.lastname: Singler
authors.forename: Annette
authors.initials: A
authors.lastname: Richard
authors.forename: Frank
authors.initials: F
authors.lastname: Wappler
authors.forename: Mark U
authors.initials: MU
authors.lastname: Gerbershagen
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D003620:Dantrolene / Q000378:metabolism / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005334:Fever / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006439:Hemodynamics; D006720:Homozygote; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism; D008305:Malignant Hyperthermia / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D000071247:Uncoupling Protein 3
chemical_list: D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071247:Uncoupling Protein 3; D003620:Dantrolene; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine