Monday September 14, 2009
Malignant Hyperthermia: Agent of choice…Dantrolene

Malignant Hyperthermia is a rare, but potentially lethal musculoskeletal disorder associated with exposure to halogenated anesthetic gases or succinylcholine. Some signs/symptoms include tachycardia, hyperthermia, supraventricular and ventricular arrhythmias, and even cardiac arrest.

The mainstay of treatment is Dantrolene. It is a direct-acting skeletal muscle relaxant that blocks calcium release from intracellular stores in the sarcoplasmic reticulum. Dantrolene is dosed 1mg/kg to a maximum cumulative dose of 10 mg/kg. Infuse over approximately 1 hour. Doses may be repeated until signs of malignant hyperthermia are reversed.

It is highly lipophilic, thus poorly soluble in water. Dantrolene is currently available for intravenous use in vials containing 20mg lyophilized dantrolene sodium added to 3 gm mannitol to improve water solubility. The contents in the vial are to be dissolved in 60 mL water, yielding a final concentration of 0.33 mg/mL. The vials are to be protected from light and should be used within 6 hours once reconstituted. Due to the high irritability, it is recommended that dantrolene be infused into a large vein. Dantrolene peaks in 6 hours, and has a half life of 12 hours. It is metabolized by liver microsomes and are excreted mainly via urine and bile.


Reference:

Krause T, et al. Anaesthesia 2004;59:364
Rosenbaum HK, et al. Anesthesiology Clin N Am 2002;20:623