Dantrolene dose response in malignant hyperthermia-susceptible (MHS) swine: method to obtain prophylaxis and therapeusis.

Abstract

The authors examined the thesis that a dose of dantrolene producing 95 per cent of maximal muscle relaxation (ED95) would effectively prevent or treat malignant hyperthermia (MH). In one group of four pigs sensitive to malignant hyperthermia (MHS) a dose response to intravenous dantrolene was determined by quantitation of toe twitch tension. From these data, the ED95 relaxant dose (3.5 mg/kg) was derived. In a second group of four MHS pigs, the ED95 dantrolene dose was administered prior to MH challenge with succinylcholine, 2 mg/kg, and halothane, 1.5 per cent. MH was prevented in each animal, while measurements of arterial pressure, arterial blood-gas, pH and lactate values, rectal temperature, and heart rate were done. Later, MH rapidly developed in the same four animals when they were again challenged. When treated with the ED95 dose, each animal survived. Finally, each pig was challenged without dantrolene prophylaxis or therapeusis, and all succumbed from MH. Previous studies have shown the efficacious use of dantrolene in prevention or treatment of porcine MH, but doses used have varied, without rationale. The present study shows that in MHS pigs the ED95 muscle relaxant dose of dantrolene (3.5 mg/kg) successfully prevents and treats MH.