Dantrolene Dose Response in Malignant Hyperthermia-susceptible (MHS) Swine

Abstract
The thesis that a dose of dantrolene [DL] producing 95% of maximal muscle relaxation (ED95) would effectively prevent or treat malignant hyperthermia (MH) was examined. In 1 group of 4 pigs sensitive to malignant hyperthermia (MHS) a dose response to i.v. DL was determined by quantitation of toe twitch tension. The ED95 relaxant dose (3.5 mg/kg) was derived. In a 2nd group of 4 MHS pigs, the ED95 DL dose was administered prior to MH challenge with succinylcholine, 2 mg/kg, and halothane, 1.5%. 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. MH rapidly developed in the same 4 animals when they were again challenged. When treated with the ED95 dose, each animal survived. Each pig was challenged without DL prophylaxis or therapeusis, and all succumbed from MH. Previous studies have shown the efficacious use of DL 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 DL (3.5 mg/kg) successfully prevents and treats MH.