Dantrolene Sodium - The Specific Treatment for Malignant Hyperthermia

WHAT IS MALIGNANT HYPERTHERMIA?

MH is a chain reaction of symptoms (a syndrome) triggered in susceptible individuals by commonly used general anesthetics and, possibly, some other drugs. The symptoms include a greatly increased body metabolism, muscle rigidity and high fever. Death may result from cardiac arrest, brain damage, internal hemorrhaging or failure of other body systems.

All of the volatile inhalation anesthetics are triggers, and the muscle relaxant succinylcholine is also a trigger. Nitrous oxide is not a trigger.


HOW IS MH TREATED?

MH had a mortality rate of nearly 80 percent at the time it was identified in 1960. Treatment consisted only of cooling the patient and treating the specific symptoms, but not the underlying cause.

Since 1979, the antidote drug dantrolene sodium has been available for the treatment of MH and has contributed greatly to a dramatic decline in mortality. The syndrome must be identified and treated early for a successful outcome. Dantrolene sodium (Dantrium IV) is manufactured by Procter & Gamble Pharmaceuticals.


HOW DOES DANTROLENE WORK?

Dantrolene is thought to reduce muscle tone and metabolism by preventing the ongoing release of calcium from the storage sites in muscle (the sarcoplasmic reticulum). In MH, intracellular calcium levels are elevated and therefore dantrolene counteracts this abnormality.

Fortunately, muscle calcium is not reduced to a level as to render the muscle flaccid and without tone. It is therefore not a muscle relaxant in the same sense as curare or analogs of curare. Dantrolene does not significantly potentiate the effects of non- depolarizing relaxants or prevent the ability to reverse curariform drugs with anticholinesterase agents.

Dantrolene may cause significant muscle weakness in patients with pre-existing muscle disease and should be used with extreme caution in those patients.

When used with calcium channel blockers, dantrolene may produce life-threatening hyperkalemia and myocardial depression. Otherwise there does not appear to be significant negative interaction with other drugs.

Once a patient has been successfully treated with intravenous dantrolene, he or she may be switched to oral dantrolene for several days.


WHO SHOULD STOCK DANTROLENE SODIUM?

Dantrolene should be available for the treatment of potential MH cases anywhere general anesthesia is administered, including hospitals and outpatient surgery centers.

HOW MUCH DANTROLENE SHOULD BE KEPT IN STOCK?

Although most cases of MH respond to 2.5-4.0 mg/kg of dantrolene initially, some patients need significantly more to bring the episode under control. In addition, recrudescence is a possibility within the first few days of treatment. Finally, because of the need for continued treatment for at least 48 hours after MH at a dose of about 1 mg/kg every 4 hours, the Malignant Hyperthermia Association of the United States (MHAUS) recommends that 36 vials be stocked.

WHERE SHOULD DANTROLENE BE KEPT?

Dantrolene should be kept in or very close to the operating room, so that it is available immediately if MH occurs. A supply of sterile water for injection USP (without a bacteriostatic agent) should be kept nearby to mix with dantrolene before injection.

ARE THERE ANY ADVANTAGES IN SHARING A SUPPLY OF DANTROLENE?

Absolutely not. Minutes count in an MH emergency. The Professional Advisory Council of MHAUS strongly recommends that an adequate supply of dantrolene be available whenever general anesthesia is administered.

Responsibility for treatment rests with the facility where the surgery is performed and, therefore, sharing is not a good alternative.


DOESN'T DANTROLENE OUTDATE TOO QUICKLY AND COST TOO MUCH TO KEEP ON HAND FOR AN OCCURRENCE WHICH IS NOT VERY LIKELY TO HAPPEN?

No. At present, dantrolene has a shelf life of three years from the date of manufacture. Although fulminant MH episodes are unusual, they do happen; and, sadly, patients still die from MH.

IS PRE-TREATMENT WITH DANTROLENE NECESSARY?

Although pre-treatment with dantrolene for known susceptibles is not usually necessary, in some situations, such as the patient who survived a crisis, some experts recommend pre-treatment with 2 mg/kg intravenously prior to induction of anesthesia.

WHAT IS THE COST OF DANTROLENE?

Dantrolene's 1993 price is approximately $46/vial. Even considering some loss of shelf life during transportation from plant to hospital, the cost of maintaining 36 vials in stock is less than $600 per year -- a tiny fraction of most hospital budgets and a very small price to pay for safety.


MHAUS HOTLINE Names and phone numbers of on-call anesthesiologists available to consult in MH emergencies may be obtained 24 hours a day through:

Medic Alert Foundation International
(209) 634-4917 Ask for Index Zero


This brochure was written and produced by the MALIGNANT HYPERTHERMIA ASSOCIATION OF THE UNITED STATES (MHAUS). MHAUS serves MH-susceptible individuals and medical professionals. MHAUS is a non-profit organization under IRS Code 501(c)(3). Its services are provided free. It operates solely on contributed funds. All contributions are tax- deductible and should be sent to:

MHAUS
PO Box 191
Westport, CT 06881-0191
(203) 847-0407


The information in this brochure is intended as a general description of MH and not as a specific recommendation for patient care or management. Consult a qualified physician for further information. 4/93