Malignant hyperthermia (MH)
Malignant hyperthermia (MH) is a genetic disorder that can trigger a life-threatening reaction during anesthesia, characterized by a rapid increase in body temperature, severe muscle contractions, and elevated heart rate. This condition is inherited in a dominant manner, meaning that an individual only needs one copy of the mutated gene, often associated with the ryanodine receptor (RYR1), to be affected. Symptoms typically do not manifest until the individual is exposed to certain anesthetic drugs, such as halothane or muscle relaxants like succinylcholine. The physiological response involves excessive calcium release within muscle cells, leading to metabolic disturbances, including the potential for rhabdomyolysis and hyperkalemia, which can critically impact heart function.
While MH cases are reported at a frequency of about one in ten thousand to one in fifty thousand in the U.S., it is often undiagnosed and may disproportionately affect younger patients. Those with a family history of MH should inform healthcare providers prior to surgery, as specific tests can confirm the presence of the condition. Immediate treatment of MH focuses on halting the triggering anesthetics and administering dantrolene, a drug that counteracts the calcium release in muscles, alongside cooling measures to manage elevated body temperature. Overall, awareness and preparedness are crucial in managing the risks associated with malignant hyperthermia in surgical settings.
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Malignant hyperthermia (MH)
Malignant hyperthermia is a genetic condition that causes a severe reaction to certain types of drugs used when a patient is given anesthesia during a surgical procedure. The condition causes a rapid rise in body temperature, severe muscle contractions, and an increase in heart rate. These symptoms put the anesthetized patient's life in danger. Without immediate treatment, the condition can prove fatal. Malignant hyperthermia is an inherited condition passed down from parent to child. It is often referred to as a pharmacogenetic disorder because the reaction is caused by drugs. The condition presents no symptoms until a person is exposed to anaesthesia drugs, and many individuals do not discover they have inherited malignant hyperthermia until after receiving anesthesia. Certain exams and tests can help identify the presence of genetic abnormalities associated with malignant hyperthermia in individuals.
Background
Malignant hyperthermia is a genetically inherited condition that affects the skeletal muscles of an individual. This abnormal gene is inherited from one parent and is characterized as a dominant genetic disorder since only a single copy of the gene is necessary to inherit the abnormality. Malignant hyperthermia less commonly occurs as the result of a new genetic mutation in an individual. Scientists have identified the ryanodine receptor (RYR1) gene as the primary location of inherited malignant hyperthermia. This gene mediates calcium release in the muscle tissues. Approximately 50 percent of malignant hyperthermia cases show mutations in this gene. Researchers have also linked the condition to abnormalities in the CACNA1S gene, a protein-coding gene located on chromosome 1. Only 1 percent of reported instances involve mutations in this gene, however.
This inherited gene triggers a bodily reaction to anesthetics, causing a chemical reaction that quickly raises body temperature and tightly contracts muscles. Anesthetic gases—such as halothane, desflurane, isoflurane, sevoflurane, and enflurane—most commonly trigger malignant hyperthermia. The condition can also be caused by muscle relaxant medications administered during anesthesia, such as suxamethonium and decamethonium. In rare instances, stressors such as vigorous exercise or high heat can cause malignant hyperthermia. High body temperature and muscle contractions are the primary symptoms of the condition, but several other complications may develop as a result.
The biological mechanisms behind malignant hyperthermia begin with the muscles. The anesthetic drugs react with muscle cells to release a large amount of calcium, which builds up in the muscle tissue and causes contractions. The body then attempts to restore the balance of calcium in the blood and begins releasing adenosine triphosphate (ATP), a high-energy molecule that stokes the body's metabolism. This leads to a rapid rise in body temperature and destruction of muscle fibers.
The frequency of reported cases of malignant hyperthermia in the United States ranges from one in ten thousand to one in fifty thousand patients. These reported frequencies were much higher in children than adults. As many instances of malignant hyperthermia go unreported or undetected, the frequency rates may be higher. Researchers suspect about seven hundred people are affected by malignant hyperthermia on an annual basis. According to records kept by the North American Malignant Hyperthermia Registry database, only eight cardiac arrests and four deaths resulted from malignant hyperthermia between 1987 and 2006. The median age of malignant hyperthermia patients that experienced these effects was twenty years. According to demographics, malignant hyperthermia is more common in men than in women. The condition is known to occur alongside other inherited muscle diseases, such as multiminicore myopathy, nemaline rod myopathy, and central core disease.
Overview
The first sign that a patient may be experiencing malignant hyperthermia is muscle contraction and rapid heart rate. This is normally followed by an elevation in body temperature. The combination of high body temperature and depletion of ATP can damage muscle cells leading to a syndrome known as rhabdomyolysis, a condition in which the contents of muscle fibers spill into the blood stream and damage the kidneys. The body also begins to produce more potassium to counteract the calcium. Too much potassium in the blood can lead to hyperkalemia, a condition that dangerously affects the heart's rhythm. Calcium overproduction also forces the body to produce excessive amounts of acid, which disturbs the blood pH balance and can lead to coma or death.
Most patients do not know they carry the gene for malignant hyperthermia until they receive anesthesia. People with a parent, sibling, or child with malignant hyperthermia have a 50 percent chance of having the condition themselves. Distant relatives, such as aunts and uncles, have a 25 percent chance of having the condition. Individuals with a known family history of malignant hyperthermia can be given specific exams and tests to determine if they have the gene. Tests for malignant hyperthermia include blood clotting studies, a blood chemistry panel, genetic testing to search for genetic defects, a muscle biopsy, or a myoglobin urine test. The most definitive test for diagnosing malignant hyperthermia is an in vitro contracture test, which biopsies a piece of leg muscle and measures its response to halothane and caffeine.
Patients with a family history of malignant hyperthermia must tell their surgeon and anesthesiologist prior to surgery. When malignant hyperthermia occurs following anesthesia, health professionals must immediately stop administering the anesthetic that triggered the reaction. A drug called dantrolene is given intravenously to inhibit further calcium release into skeletal muscle. Doctors also take measures to reduce a patient's body temperature, placing ice packs, cooling blankets, and fans around the patient to cool the body.
Bibliography
"CACNA1S Gene." Genetics Home Reference, ghr.nlm.nih.gov/gene/CACNA1S. Accessed 31 Oct. 2017.
"Malignant Hyperthermia." Mayo Clinic,www.mayoclinic.org/diseases-conditions/malignant-hyperthermia/symptoms-causes/syc-20353750. Accessed 31 Oct. 2017.
"Malignant Hyperthermia." MedlinePlus, medlineplus.gov/ency/article/001315.htm. Accessed 31 Oct. 2017.
"Malignant Hyperthermia." Medscape, emedicine.medscape.com/article/2231150-overview#a2. Accessed 31 Oct. 2017.
"Malignant Hyperthermia." National Organization for Rare Disorders, rarediseases.org/rare-diseases/malignant-hyperthermia/. Accessed 31 Oct. 2017.
"Malignant Hyperthermia." WebMD, www.webmd.com/a-to-z-guides/malignant-hyperthermia-10533. Accessed 31 Oct. 2017.
"Rhabdomyolysis." WebMD, www.webmd.com/a-to-z-guides/rhabdomyolysis-symptoms-causes-treatments#1. Accessed 31 Oct. 2017.
Rosenberg, Henry, et al. "Malignant Hyperthermia." Orphanet Journal of Rare Diseases, vol. 2, pp 21, 2007, www.ncbi.nlm.nih.gov/pmc/articles/PMC1867813/. Accessed 31 Oct. 2017.