Dantrolene

What it does?

Dantrolene is a hydantoin derivative that was originally developed for the treatment of muscle spasticity. It is poorly soluble in water and the pharmaceutical preparation for intravenous use combines 20 mg of lyophilised dantrolene with 3 g of mannitol to improve solubility.

Dosage and Formulations

In order to prepare dantrolene for injection the contents of each 20 mg vial need to be dissolved in 60 mls of sterile water. Each box of dantrolene contains 12 vials of dantrolene and 12 vials of distilled water. Once the water has been added to a vial of dantrolene, the vial must be vigourously shaken to ensure a clear solution before it is injected. The solution is highly alkaline so it should be injected through as large as vein as possible.

The initial dose of dantrolene that should be given to a suspected case of MH is 2.5 mg/Kg. Further doses of 1 mg/Kg should be given until the patient’s core body temperature is less than 38.5°C, the heart rate is decreasing, the increase in carbon dioxide production has been reversed and any muscle rigidity has resolved.

From a practical perspective, our advice for adult patients is simply to administer each prepared vial of dantrolene as it becomes available until the treatment goals are achieved. In children the initial dose of 2.5 mg/Kg should be given and subsequent doses of 1 mg/Kg given at five minute intervals until the desired response is seen. In the treatment of a malignant hyperthermia reaction there is no maximum dose of dantrolene in adults or children.

It should be noted that the unwanted signs of hypermetabolism and hyperthermia can recur after initial successful response. This recrudescence can occur up to 12 to 14 hours after the initial MH reaction and is managed by giving further doses of dantrolene.

How much Dantrolene to stock?

It is mandatory for dantrolene to be stocked on every site where general anaesthesia is administered.

The actual quantity of dantrolene stocked depends on the maximum weight of patients treated at any location. Sufficient stock of Dantrolene should be stored to treat the heaviest patients managed in a particular location. Our recommendations are as follows:

At least 2.5 mg/Kg of dantrolene should be available within five minutes of every location where general anaesthesia is administered.

At least a further 3 mg/Kg of dantrolene should be available within 20 minutes of each location where general anaesthesia is administered.

At least a further 8 mg/Kg of dantrolene should be available within 60 minutes of each location where general anaesthesia is administered.

If dantrolene is used at any location the pharmacy department should be notified immediately to ensure stocks are replenished.

Whenever local dantrolene supplies have been used, elective surgery should be delayed until stocks  are replenished.