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Malignant Hyperthermia
Sunday, 14 August 2005
Sunday, 14 August 2005

What

Malignant hyperthermia is a disorder of skeletal muscle and is characterized by prolonged muscle contraction and increased body temperature after being exposed to certain kinds of anesthesia or muscle relaxants. It is inherited in an autosomal dominant manner. Although this condition can be life-threatening, it can be treated if the symptoms are recognized early and therapy is promptly initiated.

Who

The incidence of malignant hyperthermia has been reported from 1 in 5,000 to 1 in 10,000 children and 1 in 50,000 to 1 in 100,000 adults who undergo anesthesia. There is a male predominance with a male to female ratio of 2 to 1. It is considered to be a rare condition.

Signs and Symptoms

People with malignant hyperthermia have no symptoms until they are exposed to halogenated anesthetics or depolarizing muscle relaxants, the most frequent triggers of a crisis. Examples of triggering anesthetics include halothane, isoflurane, enflurane, sevoflurane, and desflurane. Succinylcholine is an example of a depolarizing muscle relaxant. Other triggers include exercise in hot conditions, seizure medication, alcohol use and infections. Most people present with symptoms during an operation while under anesthesia. Symptoms include a sudden increase in heart rate, sudden increase in body temperature and prolonged muscle contraction. Symptoms may even present 2 ½ hours after initial exposure to the anesthesia or in the recovery room. While in recovery, the patient begins to have a gradual increase in temperature that is unexplained accompanied by muscle pain and cramping. Other patients may also experience hemolysis which is the rupture of red blood cells. Some people who have had previous exposure to the anesthestic without incidence can later develop malignant hyperthermia with subsequent exposure. Some early symptoms that may arise while under anesthesia include: rigidity of the masseter muscle found in the face, blood that is acidic due to troubled breathing, low oxygenation, increased output of carbon dioxide from the lungs, elevated muscle protein levels in the blood (myoglobin or creatine phosphokinase) or urine (myoglobin) due to muscle breakdown and heart rhythm abnormalities.

Possible Causes

Most patients with malignant hyperthermia have point mutations in the ryanodine receptor gene on chromosome 19. This gene is involved in the regulation of calcium release in the muscle. The mutated receptor allows calcium to be released from the muscle cells at an uncontrolled rate. This causes the muscles to contract for a prolonged period of time. When the muscle contracts for such a long time, the muscle cells begin to die and they release their contents which include various molecules, proteins and enzymes that can be detected in the blood (i.e. potassium, myoglobin, creatinine phosphokinase). Increased levels of these substances in the blood and the elevated body temperature are very dangerous, potentially leading to damage of organs like the kidney and the heart. Although the mutation in the ryanodine receptor gene on chromosome 19 is most common, others with malignant hyperthermia have mutations in genes on other chromosomes (chromosomes 1, 7, 3, 5, 17). The role and function of these genes that lead to malignant hyperthermia have yet to be determined.

Diagnosis

There are no specific findings to diagnose malignant hyperthermia. The diagnosis is through the clinical symptoms and certain laboratory findings such as an increased blood concentration of potassium, creatinine phosphokinase, and aldolase. Muscle biopsy will show a variety of muscle cell abnormalities to help a pathologist confirm the diagnosis.

Treatment

During a crisis the offending anesthestic is discontinued and the drug dantrolene is used to reverse the effects of muscle rigidity. Oxygenation and cooling measures are initiated, as well as corrections of the other blood abnormalities. People with a family history of malignant hyperthermia or other complications due to anesthesia should consider being screened for their risk of malignant hyperthermia. The test involves taking a muscle sample and exposing it to caffeine and halothane. The amount of contraction is measured and compared to normal samples in order to assess whether an abnormal reaction occurred. Since this test is invasive, alternative tests are under investigation but most are not used as screening tools.

Prognosis

The release of muscle cell contents and the increased body temperature during malignant hyperthermia crisis can cause multiple organs to fail, including the heart which can lead to death. However, if the symptoms are recognized early, they can be treated with minimal residual effects. Other family members should be screened to assess their own risk of malignant hyperthermia.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Malignant Hyperthermia Association of the United States
The Malignant Hyperthermia Association of the United States has a wealth of information and even has a message board. Information in Spanish is available.

Wake Forest University Baptist Medical Center
The Wake Forest University Baptist Medical Center’s informational page on malignant hyperthermia. It has a wealth of information for patients and their families as well as a variety of links to resources.

Department of Anesthesiology at UCLA
This is a technical but informational page from the Department of Anesthesiology at UCLA. UCLA is one of a few centers at which the muscle contracture test can be performed.

Google Search for Malignant Hyperthermia

References and Sources

www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=145600 www.amjforensicmedicine.com/pt/re/ajfmp/fulltext.00000433-200412000-00010.htm;jsessionid=C191fB2tpZraUrPcJOTwtgaabrRb2Vxhv9uE2APEwzug4VVKaUXD!250931426!-949856145!9001!-1 (Christiansen LR, Collins KA. Pathologic findings in malignant hyperthermia: a case report and review of literature. Am J Forensic Med Pathol. 2004 Dec;25(4):327-33.)