Dantrolene Sodium - The Specific Treatment for Malignant
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 &
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
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
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
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.
Names and phone numbers of on-call
anesthesiologists available to consult in MH
emergencies may be obtained 24 hours a day
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:
PO Box 191
Westport, CT 06881-0191
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.