Última actualización:
5/8/2026
Años publicados: 1984, 1988, 1989, 1990, 1992, 1999, 2005, 2009, 2013, 2026
NORD gratefully acknowledges Daniel Lu and Caden Baudek, editorial interns from the University of Notre Dame and Sheila Riazi, MSc, MD, FRCPC and Cezar Daniel snak de Souza, MD of the Malignant Hyperthermia Investigation Unit, University Health Network, Toronto, Canada for their assistance in the preparation of this report.
Malignant Hyperthermia (MH) is a rare inherited disorder of skeletal muscle that places susceptible individuals at risk for a life-threatening reaction when exposed to certain anesthetic agents. These triggering agents include volatile inhaled anesthetics (such as sevoflurane, desflurane, isoflurane, and halothane, among others) and the depolarizing muscle relaxant succinylcholine.1, 2
Without prompt recognition and treatment, MH can result in severe complications, including rhabdomyolysis (breakdown of muscle tissue), kidney failure, cardiac arrest, and death. However, with early diagnosis and immediate treatment using intravenous dantrolene, outcomes have improved substantially over the past several decades.3, 4
MH is classically characterized by signs and symptoms that appear after being exposed to the triggering agents. Though not all signs appear in every case, and the timing of symptom development varies widely from minutes to hours after exposure. Signs and symptoms may include:
Even though the condition is called “hyperthermia” (which means a very high body temperature), a fever often shows up later and may not be present at the beginning. In adults, the earliest and most common warning sign is a rise in end-tidal carbon dioxide, which is the amount of carbon dioxide you breathe out at the end of each breath. If this level stays high even when breathing is increased to try to remove more carbon dioxide, it can be an early clue that something is wrong.3, 5, 6
In children, the signs can look different depending on age. Babies and infants (0–24 months) are more likely to show an early rise in body temperature. Children aged 2–12 years often develop muscle-related symptoms, such as a tight or locked jaw (called a masseter spasm), stiffness throughout the body (muscle rigidity). Teenagers (13–18 years) tend to present more like adults, with high levels of carbon dioxide in their exhaled breath and a fast heart rate (sinus tachycardia, meaning the heart is beating quicker than normal but still in a regular rhythm). 7,8
Malignant hyperthermia is a disorder of abnormal calcium regulation in skeletal muscle, primarily caused by changes (variants) in the ryanodine receptor type 1 (RYR1) gene and, less frequently, in the CACNA1S gene, which encodes the alpha-1 subunit of the dihydropyridine receptor (L-type calcium channel). During normal muscle contraction, an electrical signal causes the release of a small amount of calcium to help the muscle flex. Certain anesthesia medicines can disrupt the process causing too much calcium to enter the muscle at one time leading to sustained, uncontrolled contractions.9
Inheritance
The MH trait is passed down as an autosomal dominant trait, but not everyone who has the gene change will show symptoms. This means some people with the gene variant may never have any physical problems or episodes. Dominant genetic disorders occur when only a single copy of a gene variant is necessary to cause a particular disease. The variant gene can be inherited from either parent or can be the result of a new genetic change in the affected individual. The risk of passing the variant gene from affected parent to offspring is 50% for each pregnancy (assuming the parent only has one copy of the variant gene). The risk of inheriting the gene is the same for males and females.
The incidence of MH is estimated at 1 per 100,000 general anesthetics under triggering conditions (with some estimates citing 1:10,000 in children and 1:50,000 in adults), while the prevalence of pathogenic or likely pathogenic RYR1 variants in the general population is estimated at 1 in 1,000 individuals.10 This difference means that many people who carry the gene never actually develop MH. In other words, having the genetic change does not always lead to symptoms (incomplete penetrance), and when it does, the severity can vary widely from person to person (variable expressivity).11
Diagnosis of malignant hyperthermia begins with obtaining a thorough personal and family history of adverse anesthetic events. The doctor should specifically inquire about unexplained perioperative deaths, episodes of hyperthermia during anesthesia, prolonged recovery from anesthesia, or complications such as rhabdomyolysis in both the patient and blood relatives, as many MH-susceptible individuals have a positive family history.20, 21
During an acute episode, the most common initial clinical sign is an unexplained rise in end-tidal carbon dioxide that does not respond to ventilation support, followed by tachycardia, muscle rigidity (particularly masseter spasm after succinylcholine), hyperthermia, and signs of hypermetabolism.20, 22
Genetic testing should be offered to all patients with either a personal or family history of severe adverse events related to anesthesia. Up to 70% of patients diagnosed with MH-susceptibility by contracture testing harbour one or more diagnostic variants in the RYR1 or CACNA1S genes.23, 24 Identifying a genetic variant classified as pathogenic or likely pathogenic for MH confirms the high-risk status and precludes the need for additional testing. For patients with a high degree of suspicion despite a negative genetic test result, the gold standard for diagnosis of MH susceptibility is the surgical muscle biopsy followed by muscle contracture testing with caffeine and halothane. This is a reliable (>95% sensitivity), although invasive method for diagnosing MH susceptibility. It requires fresh, surgically excised muscle and specialized laboratory technique.25, 26 MH susceptibility indicates a high risk for an MH event but does not guarantee adverse reaction.
A malignant hyperthermia (MH) episode is a medical emergency requiring immediate intervention. The first and most critical step is the prompt discontinuation of all triggering agents, including volatile anesthetic gases and succinylcholine. Anesthesia should be continued with non-triggering agents, and the anesthesia machine should be flushed with 100% oxygen. Activated charcoal filters may be placed to reduce residual anesthetic vapour exposure. The cornerstone of treatment is the rapid administration of intravenous dantrolene. Dantrolene is a muscle relaxant that blocks calcium release from the ryanodine receptor, halting the calcium release cascade.
Supportive care is essential and includes active cooling (e.g., infusion of cold crystalloid, placement of ice packs), management of increased potassium levels (hyperkalemia) and malignant arrhythmias, correction of acid buildup in the blood (metabolic acidosis), and monitoring and support of kidney function due to the risk of rhabdomyolysis (i.e., sodium bicarbonate infusion, dialysis).27
Although dantrolene is FDA-approved for preoperative prophylaxis in MH-susceptible individuals, current clinical practice generally favors the avoidance of all known triggering agents (volatile anesthetics and succinylcholine) combined with the immediate availability of dantrolene for treatment, rather than routine prophylactic administration. Further details about MH treatment and more information about MH for patients and physicians are available at the following URL: http://www.MHAUS.org.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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