Malignant hyperthermia occurs when a rare, inherited muscle abnormality causes a severe and sometimes fatal reaction to a dose of anesthetics. Infrequently, extreme exercise or heat stroke, instead of an anesthetic, can trigger malignant hyperthermia in someone who has this muscle abnormality.

In people with the muscle abnormality, a gene mutation causes muscle cells to have an abnormal protein on their surfaces. The mutation does not affect muscle function significantly until the muscles are exposed to one of several drugs that can trigger a reaction. When a person with this condition is exposed to one of these drugs, calcium stored in muscle cells is released, causing the muscles to contract and stiffen at the same time, causing a dramatic and dangerous increase in body temperature (hyperthermia).

Medications known to trigger malignant hyperthermia are succinylcholine (Anectine), which is a muscle relaxant used during surgery, and certain inhaled anesthetics, including halothane (Fluothane), enflurane (Ethrane), isoflurane (Forane), methoxyflurane (Penthrane), sevoflurane (Ultane) and desflurane (Suprane).

Although malignant hyperthermia most often occurs during or after surgery, it can occur wherever anesthetic medications are used, such as in emergency rooms, dental offices, surgeons' offices and intensive care units. Symptoms of malignant hyperthermia usually occur within the first hour after a medication that can trigger the disorder is administered, although the symptoms can be delayed for up to 12 hours.

Most cases of malignant hyperthermia occur in children and adults younger than 30. It has been estimated to occur once in every 15,000 surgeries in children and less often in adults.

There are several gene mutations that can cause this muscle abnormality. This condition sometimes occurs in people who also have one of various forms of muscular dystrophy or another muscle disease associated with genetic mutations. People with such muscle disorders are thought to be at a higher risk of malignant hyperthermia.

The most common mutation, which causes about half of all cases of malignant hyperthermia, is transmitted in what geneticists call an autosomal dominant pattern. This means that a person with the mutation has a 50% chance of passing the gene to any of his or her children. It also means that each sibling of an affected person has a 50% chance of also having the gene.

Family members can have different levels of sensitivity to medications that trigger the problem. In some cases, reactions are mild, so a person may be exposed to high-risk medications several times before experiencing a reaction that is severe enough to be recognized.

The term malignant hyperthermia usually is used to describe only this problem caused by a gene mutation. However, some doctors also use the term when extreme hyperthermia (increase in body temperature) happens in a person without a gene mutation. Problems that can cause this to happen include:

• Heat stroke
• Drug overdose (especially MDMA, or ecstasy)
• Neuroleptic malignant syndrome, a rare condition in which fever and muscle stiffness are triggered by exposure to certain psychiatric medications

Symptoms of malignant hyperthermia include:

• A dramatic rise in body temperature, sometimes as high as 113 degrees Fahrenheit
• Rigid or painful muscles, especially in the jaw, but possibly also in the arms, legs, abdomen and chest
• Flushed skin
• Sweating
• An abnormally rapid or irregular heartbeat
• Rapid breathing or uncomfortable breathing
• Brown or cola-colored urine
• Very low blood pressure (shock)
• Confusion or coma
• A patchy purple tint to the skin or a purple tint to the lips and fingernails
• Neurological symptoms, such as weakness or seizure
• Muscle weakness or swelling after the event

Episodes of malignant hyperthermia develop when a triggering medication is given to a person with the condition. However, many of those who carry a gene for malignant hyperthermia will never develop symptoms. In addition, not all symptoms will develop during each episode of malignant hyperthermia.

Most people with malignant hyperthermia are not diagnosed until they have a serious reaction to general anesthesia. Doctors usually will suspect this condition if a patient develops any of the typical symptoms, particularly high fever or rigid muscles. Blood tests that show changes in the body chemistry, such as electrolyte changes, can give doctors clues that muscle metabolism is increasing. Blood tests that show signs of kidney failure also can provide clues. If malignant hyperthermia is not recognized and treated quickly, the person's heart may stop during surgery.

If you experience most or all of the typical symptoms of malignant hyperthermia, your doctor may diagnose this condition without additional testing. It is also possible to use a muscle biopsy to confirm the diagnosis. A tiny piece of muscle is removed from your thigh and checked for its reaction to caffeine and to the anesthetic halothane. A positive reaction to this caffeine-halothane test strongly suggests that you have malignant hyperthermia. The caffeine-halothane test is done at fewer than a dozen special laboratories in the United States, and it can be performed accurately only on a fresh biopsy sample that is no more than a few hours old. For this reason, you may have to travel to have the test done.

If doctors suspect malignant hyperthermia and begin treatment promptly, symptoms should resolve within 12 to 24 hours. However, if a severe reaction develops before treatment is started, complications such as respiratory or kidney failure may develop. These complications may not improve for days or weeks, and some damage may be permanent.

The anesthetics that can trigger malignant hyperthermia remain useful and are used widely because malignant hyperthermia is rare. It is not practical to test for this condition in all people who are scheduled for surgery. However, some people should be tested before surgery or should avoid anesthetics that are known to cause this condition. They include people with a family history of malignant hyperthermia, a history of heat stroke or hyperthermia after exercise, or muscle abnormalities that may be associated with malignant hyperthermia.

If you do not have a family history of malignant hyperthermia, your first episode may not be predictable or preventable.

Once malignant hyperthermia has been diagnosed, further episodes can be prevented. If you know that you have malignant hyperthermia or that a close family member has been diagnosed with the condition, notify your health care professional before you undergo any surgery or office-based procedure. This will allow your doctor or dentist to avoid using succinylcholine or high-risk anesthetics. It is not necessary to avoid surgery altogether, because many safe alternative anesthetics are available. If you know that you are susceptible to malignant hyperthermia, consider wearing a medical alert tag to advise health care personnel about your condition during an emergency.

If you plan to travel outside the United States, you can contact the Malignant Hyperthermia Association of the United States to determine whether doctors at your travel destination are aware of the condition and equipped to treat it. This is a sensible precaution because malignant hyperthermia is a rare disease and has been recognized relatively recently. If the Malignant Hyperthermia Association of the United States is unsure about the reliability of medical care in the country you plan to visit, you may want to carry information about malignant hyperthermia with you when you travel, together with the phone number of the Malignant Hyperthermia Association of the United States or another reliable source of information.

As soon as malignant hyperthermia is suspected, doctors must act rapidly to treat the condition and prevent complications. The first and most important step is to immediately stop giving the anesthetic medication that triggered the reaction and to stop the surgery. Doctors then give the drug dantrolene (Dantrium), which relaxes the muscles and stops the dangerous increase in muscle metabolism. Dantrolene initially is given intravenously. Once a patient has stabilized, the medication typically is continued in pill form for three days.

Additional treatment for malignant hyperthermia can include:

• Lowering body temperature with cool mist and fans, cooling blankets or cooled intravenous fluids
• Administering oxygen
• Using medications to control the heartbeat or stabilize blood pressure
• Monitoring in an intensive care unit

You should tell your surgeon, your primary care doctor and your anesthesiologist prior to any surgery if you:

• Have a family history that includes malignant hyperthermia
• Have had one or more episodes of heat stroke or exercise-induced hyperthermia
• Have muscle symptoms or a known muscle disease

Malignant hyperthermia can lead to cardiac arrest, brain damage and organ failure. When the condition was first described in 1960, nearly 80% of patients died. Now, with a combination of earlier diagnosis and dantrolene treatment, fewer than 10% of patients die of malignant hyperthermia.

Malignant Hyperthermia Association of the United States
11 East State St.
P.O. Box 1069
Sherburne, N.Y 13460
Phone: 607-644-9737
Toll-Free: 1-800-644-9737
Fax: 607-674-7910
Email: info@mhaus.org
http://www.mhaus.org/

National Institute of Arthritis and Musculoskeletal and Skin Diseases
Information Clearinghouse
National Insitutes of Health
1 AMS Circle
Bethesda, MD 20892-3675
Phone: 301-495-4484
Toll-Free: 1-877-226-4267
Fax: 301-718-6366
TTY: 301-565-2966
Email: niamsinfo@mail.nih.gov
http://www.niams.nih.gov/

National Organization for Rare Disorders (NORD)
55 Kenosia Ave.
P.O. Box 1968
Danbury, CT 06813-1968
Phone: 203-744-0100
Toll-Free: 1-800-999-6673
TTY: 203-797-9590
Fax: 203-798-2291
Email: orphan@rarediseases.org
http://www.rarediseases.org/