Rationale for Dantrolene vs.Procainamide for Treatment of Malignant Hyperthermia

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Abstract
The use of procainamide or procaine for treatment of malignant hyperthermia is commonly recommended. The skeletal muscle relaxant dantrolene has also been indicated for treatment of this complication during anesthesia. Effects of procainamide and dantrolene were compared in malignant hyperthermia-susceptible (MHS) pigs in vivo and on MHS muscle from human patients in vitro. The ED50 for dantrolene block of indirectly evoked twitch tension was 0.85 mg/kg in MHS pigs. A final cumulative dose of 2 mg/kg resulted in 68% block of the twitch response. Procainamide at a final cumulative dose of 14 mg/kg had no effect on twitch response of the MHS pigs. Dantrolene, 3 .mu.M, in vitro (approximately 0.8 mg/kg in vivo) was effective in preventing or reversing the abnormal halothane-induced contracture response of human MHS muscle strips. Procainamide, 0.11 mM, a dose approximating clinical levels (about 22 mg/kg), had no effect on basal twitch response or on the abnormal halothane-induced contracture of MHS human muscle. The effectiveness of dantrolene and the lack of effectiveness of procainamide in the treatment of malignant hyperthermia were confirmed.

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