From the Guidelines
Dantrolene (Dantrium) is primarily used to treat malignant hyperthermia (MH), a rare but life-threatening medical emergency that can occur during general anesthesia.
Key Uses of Dantrolene
- Reversing the MH process: Dantrolene inhibits the excessive release of calcium into the muscle cell, which is a key factor in the development of MH 1.
- Emergency treatment: Dantrolene is administered intravenously (i.v.) to treat suspected or confirmed MH reactions, with a recommended dosing regimen of 2-2.5 mg/kg based on actual body weight, up to a maximum of 300 mg per dose 1.
- Prevention of MH crises: Dantrolene should be readily available wherever volatile anaesthetic agents or succinylcholine are used, with a recommended stock of 36 vials immediately available and a further 24 vials available within 1 hour 1.
Important Considerations
- Prompt treatment is crucial: Delay in commencing treatment of MH is associated with increased mortality and the severity and number of complications 1.
- Dantrolene administration: The dosing regimen of dantrolene should be based on actual body weight, and the medication should be given i.v. as soon as possible after the diagnosis of MH is made 1.
- Availability of dantrolene: Dantrolene should be available at all locations where succinylcholine is used routinely, except in pre-hospital emergency settings where it may not be practical to carry a supply of dantrolene 1.
From the FDA Drug Label
INDICATIONS AND USAGE: Dantrium Intravenous is indicated, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. Dantrium Intravenous is also indicated preoperatively, and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible.
The use of Dantrolene (Dantrium) is for the management and prevention of malignant hyperthermia crises in patients of all ages. The main indications are:
- Management of malignant hyperthermia crises
- Prevention of malignant hyperthermia in susceptible individuals, preoperatively and postoperatively 2
From the Research
Uses of Dantrolene
- Dantrolene is used to treat malignant hyperthermia, a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia 3, 4, 5, 6.
- It is also used to treat neuroleptic malignant syndrome, a rare but life-threatening side effect of neuroleptic drugs 3, 5, 6.
- Dantrolene is used to manage muscle spasticity, particularly in patients with multiple sclerosis, although it may not be effective in all cases and can cause hepatic toxicity 3, 5.
- It has also been used to treat heat stroke and Ecstasy intoxication 3.
- Dantrolene works by suppressing Ca2+ release from ryanodine receptors (RyRs) in skeletal muscle, which helps to reduce intracellular calcium concentration and alleviate symptoms of malignant hyperthermia and other conditions 4, 5, 6.
Administration and Formulation
- Dantrolene is typically administered intravenously in emergency situations, although it can be difficult to prepare due to its poor water solubility 4, 5, 6.
- A new formulation has been developed that enhances the hydrophilicity of dantrolene, making it easier to administer 4.
- Dantrolene is also available in oral form for the treatment of muscle spasticity 4.
Metabolism and Side Effects
- Dantrolene is metabolized in the human liver by aldehyde oxidase 1 (AOX1) and N-acetyltransferase (NAT) 2, which can lead to the formation of hydroxylamine and potentially cause liver injury 7.
- Long-term use of dantrolene has been associated with hepatic toxicity, and patients should be monitored closely for signs of liver damage 3, 7.