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British Journal of Anaesthesia, 2003, Vol. 91, No. 2 281-284
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia

Short Communications

Effects of a 5HT2 receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia

M. U. Gerbershagen*,1, F. Wappler1, M. Fiege1, K. Kolodzie1, R. Weißhorn1, W. Szafarczyk1, C. Kudlik2 and J. Schulte am Esch1

1 Department of Anaesthesiology, University Hospital Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany. 2 Department of Surgery, Asklepios Westklinikum Hamburg, Suurheid 20, D-22559 Hamburg, Germany

Corresponding author. E-mail: gerbershagen@uke.uni-hamburg.de

Background. The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT2A) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.

Methods and results. DOI 1 mg kg–1 was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (PaCO2), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by PaCO2 above 70 mm Hg and an increase in body temperature of more than 2 °C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann–Whitney U-test (statistical significance P<0.05). MHS and MHN pigs developed muscle fasciculations, significant increases in body temperature and PaCO2 and a significant decrease in pH after the administration of DOI. These changes were comparable in both groups until the third dose of DOI, when in MHS pigs heart rate and PaCO2 rose significantly and pH fell significantly compared with MHN pigs. All MHS pigs fulfilled the MH criteria. Body temperature increased by more than 2 °C in all MHN pigs and PaCO2 exceeded 70 mm Hg in two. Thus, two MHN pigs fulfilled the criteria of MH.

Conclusions. The comparability of the clinical presentation following DOI administration in MHS and MHN animals and the order of the development of MH-like symptoms favour the hypothesis of a central serotonergic overstimulation, leading to a serotonin syndrome.

Br J Anaesth 2003; 91: 281–4


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