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Dantrolene dose response in malignant hyperthermia-susceptible (MHS) swine: method to obtain prophylaxis and
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.
Insights
The 95% maximal muscle relaxation dose of dantrolene (ED95) effectively prevents and treats malignant hyperthermia (MH) in pigs. This study confirms the ED95 dose (3.5 mg/kg) as a reliable strategy for managing MH.
Area of Science:
- Veterinary Anesthesiology
- Pharmacology
- Malignant Hyperthermia Research
Background:
- Malignant hyperthermia (MH) is a severe hypermetabolic crisis.
- Dantrolene is a known treatment for MH, but optimal dosing remains debated.
- Previous studies on porcine MH models used variable dantrolene doses without clear rationale.
Purpose of the Study:
- To determine if the dantrolene dose eliciting 95% maximal muscle relaxation (ED95) can effectively prevent or treat malignant hyperthermia (MH).
- To establish a rational, evidence-based dose for dantrolene in managing MH in a porcine model.
Main Methods:
- Dose-response assessment of intravenous dantrolene in malignant hyperthermia-susceptible (MHS) pigs to determine the ED95 relaxant dose.
- Administering the derived ED95 dantrolene dose (3.5 mg/kg) to MHS pigs prior to MH challenge with succinylcholine and halothane.
- Monitoring physiological parameters including arterial pressure, blood gases, pH, lactate, temperature, and heart rate during MH challenges.
- Evaluating the efficacy of the ED95 dose in both preventing and treating MH, and comparing outcomes to untreated challenges.
Main Results:
- The ED95 dose of dantrolene was determined to be 3.5 mg/kg in MHS pigs.
- Prophylactic administration of the ED95 dantrolene dose successfully prevented MH in all challenged pigs.
- Treatment with the ED95 dantrolene dose rapidly resolved MH and ensured survival in all animals.
- Untreated MH challenges resulted in mortality in all pigs, highlighting the critical role of dantrolene.
Conclusions:
- The ED95 muscle relaxant dose of dantrolene (3.5 mg/kg) is a highly effective and rational dose for both preventing and treating malignant hyperthermia in susceptible pigs.
- This study provides a clear, evidence-based dosing strategy for dantrolene in managing MH, applicable to porcine models and potentially translatable to clinical settings.