What clinical signs should the anesthesia team monitor that indicate the early onset of malignant hyperthermia?

The earliest clues are a sudden, unexplained rise in end‑tidal CO₂ despite adequate ventilation, rapid increase in heart rate, and muscle rigidity—especially a “masseter spasm” (tight jaw). A temperature rise often follows, but hypercapnia and tachycardia appear first and should prompt immediate evaluation for MH.

If malignant hyperthermia is suspected intra‑operatively, what is the standard emergency treatment protocol?

The cornerstone is immediate discontinuation of all triggering agents (volatile anesthetics and succinylcholine) and hyperventilation with 100 % oxygen. Dantrolene sodium is given intravenously—initially 2.5 mg/kg, repeated every 5 minutes until the crisis abates, up to a total of 10 mg/kg. Simultaneously, cool the patient (ice packs, cold IV fluids), correct acidosis with bicarbonate, monitor electrolytes, and treat hyperkalemia or rhabdomyolysis as needed.

Am I automatically at risk for malignant hyperthermia if a family member had an episode, or do I need specific testing before surgery?

family history of malignant hyperthermia (MH) is a strong red flag, but susceptibility is confirmed with a specialized test called the caffeine‑halothane contracture test (CHCT) performed on a muscle biopsy, or by genetic testing for known RYR1 or CACNA1S mutations. If testing isn’t feasible, you should inform the anesthesiologist of the family history so they can avoid triggering agents and have dantrolene readily available.

After surviving a malignant hyperthermia episode, what follow‑up steps should I take to protect myself in future medical procedures?

You should be referred to a center that can perform MH susceptibility testing (genetic panel or CHCT). Once confirmed, you’ll receive a medical alert bracelet and a written “MH‑susceptible” letter for all healthcare providers. Future surgeries must use non‑triggering anesthetics (e.g., total intravenous anesthesia with propofol) and have dantrolene on hand. Regular follow‑up includes renal function checks because rhabdomyolysis can affect the kidneys.

Malignant hyperthermia

Malignant hyperthermia is a severe, potentially life‑threatening reaction to certain anesthetic gases that triggers a rapid rise in body temperature, heart rate, and muscle rigidity. Prompt recognition and cessation of the trigger are essential to prevent organ failure.

Overview

Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of muscle tissue (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life‑threatening.

People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). Malignant hyperthermia may not occur every time anesthesia is used. Many individuals who develop a severe reaction have previously been exposed to a triggering drug and not had a reaction.

Affected individuals may be at increased risk for “awake” malignant hyperthermia, in which the severe reaction occurs in response to physical activity, often while sick, rather than in reaction to exposure to a triggering drug.

While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility.

Symptoms

Rapid increase in heart rate
Elevated body temperature (hyperthermia)
Abnormally fast breathing
Muscle rigidity
Rhabdomyolysis (breakdown of muscle tissue)
Acidosis (increased acid levels in blood and tissues)

Causes & Risk Factors

Certain variations of the RYR1 and CACNA1S genes increase the risk of developing malignant hyperthermia. Mutations in the RYR1 gene account for most cases of malignant hyperthermia susceptibility, while mutations in the CACNA1S gene cause less than 1 percent of all cases of malignant hyperthermia susceptibility.

The RYR1 and CACNA1S genes provide instructions for making proteins that play essential roles in muscles used for movement. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain charged atoms (ions) in muscle cells. The proteins produced from the RYR1 and CACNA1S genes are involved in the movement of calcium ions within muscle cells. In response to certain signals, the CACNA1S protein helps turn on (activate) the RYR1 channel. When the RYR1 channel is active, it releases calcium ions from storage into the fluid‑filled space inside muscle cells. The resulting increase in calcium ion concentration inside the cells stimulates muscles to contract.

Mutations in the RYR1 or CACNA1S gene cause the RYR1 channel to open more easily and close more slowly in response to certain drugs. As a result, abnormally large amounts of calcium ions are released from storage within muscle cells. The abnormal increase in calcium ion concentration within muscle cells activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). An overabundance of calcium ions also causes skeletal muscles to contract, which leads to muscle rigidity.

Up to half of people with malignant hyperthermia susceptibility do not have a mutation in one of the known genes. The causes of these cases are still under study.

Learn more about the genes associated with Malignant hyperthermia

CACNA1S
RYR1

Frequency

Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that would trigger a reaction and bring them to medical attention.

Inheritance

Malignant hyperthermia susceptibility is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery. In most cases, an affected person inherits the altered gene from a parent who is also at risk for the condition.

Other Names for This Condition

Anesthesia related hyperthermia
Hyperpyrexia, malignant
Hyperthermia, malignant
Malignant hyperpyrexia
MHS

Resources

Genetic Testing Information

Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 1
Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 4
Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 5
Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 6

Genetic and Rare Diseases Information Center

King-Denborough syndrome
Malignant hyperthermia of anesthesia

Patient Support and Advocacy Resources

National Organization for Rare Disorders (NORD)

Clinical Trials

ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1; MHS1
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 2
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 3
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 4
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 5; MHS5
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 6

Scientific Articles on PubMed

Ellinas H, Albrecht MA. Malignant Hyperthermia Update. Anesthesiol Clin. 2020 Mar;38(1):165-181. doi: 10.1016/j.anclin.2019.10.010.
Kraeva N, Sapa A, Dowling JJ, Riazi S. Malignant hyperthermia susceptibility in patients with exertional rhabdomyolysis: a retrospective cohort study and updated systematic review. Can J Anaesth. 2017 Jul;64(7):736-743. doi: 10.1007/s12630-017-0865-5.
Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. 2005 Jun 15;293(23):2918-24. doi: 10.1001/jama.293.23.2918.
Riazi S, Biesecker LG, Rosenberg H, Dirksen RT. Nonsyndromic Malignant Hyperthermia Susceptibility. 2003 Dec 19 [updated 2025 Aug 7]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.
Riazi S, Kraeva N, Hopkins PM. Malignant Hyperthermia in the Post-Genomics Era: New Perspectives on an Old Concept. Anesthesiology. 2018 Jan;128(1):168-180. doi: 10.1097/ALN.0000000000001878.
Riazi S, Kraeva N, Hopkins PM. Updated guide for the management of malignant hyperthermia. Can J Anaesth. 2018 Jun;65(6):709-721. doi: 10.1007/s12630-018-1108-0.
Treves S, Anderson AA, Ducreux S, Divet A, Bleunven C, Grasso C, Paesante S, Zorzato F. Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders. Neuromuscul Disord. 2005 Oct;15(9-10):577-87. doi: 10.1016/j.nmd.2005.06.008.
Zaharieva IT, Sarkozy A, Munot P, Manzur A, O'Grady G, Rendu J, Malfatti E, Amthor H, Servais L, Urtizberea JA, Neto OA, Zanoteli E, Donkervoort S, Taylor J, Dixon J, Poke G, Foley AR, Holmes C, Williams G, Holder M, Yum S, Medne L, Quijano-Roy S, Romero NB, Faure J, Feng L, Bastaki L, Davis MR, Phadke R, Sewry CA, Bonnemann CG, Jungbluth H, Bachmann C, Treves S, Muntoni F. STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility. Hum Mutat. 2018 Dec;39(12):1980-1994. doi: 10.1002/humu.23635.
Zvaritch E, Gillies R, Kraeva N, Richer M, Jungbluth H, Riazi S. Fatal awake malignant hyperthermia episodes in a family with malignant hyperthermia susceptibility: a case series. Can J Anaesth. 2019 May;66(5):540-545. doi: 10.1007/s12630-019-01320-z.