Dantrolene in Human Malignant Hyperthermia. A Multicenter Study

Abstract

Anesthesiologists from 65 institutions participated in a multicenter study to assess the efficacy of lyophilized intravenous dantrolene sodium in treating anesthetically related malignant hyperthermia (MH). Of 21 patients treated with the drug, eight were judged to have unequivocal MH and were treated according to study protocol. Three were judged to have probable MH and were also treated according to study protocol. All 11 recovered without sequelae from MH and without adverse drug effects. A mean dantrolene dose of 2.5 mg/kg in these patients produced significant changes in clinical and biochemical parameters suggestive of decreased cellular metabolism. Four patients with unequivocal MH were treated with intravenous dantrolene more than 24 h after the diagnosis of MH; this delay in treatment of clinical signs in these patients, the mortality rate was 75 per cent, which is comparable to that reported without dantrolene. The six remaining patients had episodes of questionable MH during or subsequent to anesthesia and were treated with dantrolene. There was insufficient evidence to justify an unequivocal or probable diagnosis of MH, and they, therefore, were not included in the study. All survived and had no adverse drug reactions. Dantrolene therapy resulted in a statistically significantly lower mortality rate than would be expected in MH patients. The study supports animal data suggesting that dantrolene is specific in reversing MH.