What Is Malignant Hyperthermia


Malignant hyperthermia is a rare, life-threatening bodily reaction following the administration of general anaesthetic drugs during surgery.

Causes of malignant hyperthermia

Malignant hyperthermia occurs when the skeletal muscles of the body react abnormally in response to exposure of strong inhaled general anaesthetic agents (drugs that put you to sleep) or succinylcholine (suxamethonium), which is a muscle relaxant most used during surgery.

Skeletal muscle is the term used to describe all the muscles in the body that connect to bones. Skeletal muscles are  muscles that allow you to consciously move your body and perform specific actions. For example, the triceps is a skeletal muscle that allows you to straighten your arm. Skeletal muscles are also called striated muscles.

Normally, a muscle cell is stimulated by a nerve signal that triggers a mass release of calcium ions. These calcium ions bind to filaments within the muscle and cause it to contract and shorten.

However, some people have an abnormal gene which causes an excessive release of calcium, resulting in excessive muscle contraction. This is the basis of the syndrome. People with this gene are said to be MH-susceptible.

When MH-susceptible individuals are exposed to strong inhaled anaesthetics like sevoflurane and halothane, or the muscle relaxant succinylcholine (suxamethonium), their skeletal muscle cells react abnormally. The muscle cells release excessively high levels of calcium, leading to increased skeletal muscle contraction. Because the calcium released is so high, the muscles continue to contract, and can eventually break down and die, which is a process called rhabdomyolysis

Sustained or untreated rhabdomyolysis can lead to kidney failure and eventually, death. The cellular processes around calcium release and uptake also generate heat, which is where the ‘hyperthermia’ aspect of the syndrome comes in. Increased body temperature can cause metabolic problems, as well as cause irreversible injury to organs, which can also be fatal. See the ‘Complications’ section for further complications.

Skeletal muscle makes up around 40% of total body weight,1 which explains in part why malignant hyperthermia can be so life-threatening. There is a huge relative mass of skeletal muscle that is in a hypermetabolic state (metabolising at a high rate) and can very quickly affect multiple body systems.

Read on to learn more about this syndrome.

Risk factors

The strongest risk factor for an episode of malignant hyperthermia is a previous episode of malignant hyperthermia. Having a family member who has been said to be ‘MH-susceptible’ is also a risk factor.

Malignant hyperthermia is inherited in an autosomal dominant pattern, meaning that if a person has one copy of the abnormal gene, they will be affected by the condition. If an affected individual has a child with an unaffected individual (no copies of the abnormal gene), then there is a 50% chance of passing on the abnormal gene.  

There is a link between malignant hyperthermia and exertional heat stroke, a syndrome that includes hyperthermia and confusion, which typically occurs after intense activity. 45.6% of the subjects who had experienced exertional heat stroke were also MH-susceptible.2 So far, the nature of the exact link between the two syndromes is unclear, but the finding that almost half of a cohort of patients with EHS were also MH-susceptible may indicate that there is an increased chance of having an underlying MH-susceptibility.

Central Core Disease has also been shown to be associated with MH-susceptibility.3,4,5 Central Core Disease is a rare, genetic disease that affects the muscles.

Signs and symptoms of malignant hyperthermia

It can be difficult to identify when a patient is having an episode of malignant hyperthermia due to the extreme variability of the associated signs and symptoms.5 Malignant hyperthermia can occur at any time during and shortly after administration of the causative drugs, extending to shortly after surgery whilst the patient is in early recovery.

As is to be expected, considering the name of the condition, a classical sign is significant hyperthermia (raised body temperature) of usually at least 40 degrees Celsius (109 degrees Fahrenheit). However, hyperthermia appears as an early symptom in some, but as a late sign in others, meaning that by the time this symptom appears, the patient is likely more unwell and has a worse prognosis. The variability of its onset makes it an unreliable predictor of the severity or stage of malignant hyperthermia.

Other signs and symptoms include:

  • Muscle rigidity or stiffness: Notably, the masseter muscles (muscles of the jaw) can become extremely rigid, making it difficult to open or close the mouth
  • Fast heart rate (tachycardia)
  • Fast breathing (tachypnoea)

For the anaesthetist, there are specific clinical features that present whilst the patient is being monitored during surgery:

  • Acidosis
  • Hyperkalaemia
  • Increased end-expired carbon dioxide

The syndrome can present very suddenly and progress rapidly, or appear gradually, so it is important for the anaesthetist to monitor the patient closely following administration of the aforementioned anaesthetic agents.6


Malignant hyperthermia presents only in response to exposure to the aforementioned anaesthetic agents (and very occasionally in response to stress, exercise, and high temperatures).7 As such, it is very difficult to identify individuals at risk of having an acute MH crisis before the crisis occurs, unless there is a family history of malignant hyperthermia, or a personal history of a reaction to anaesthetic agents.

Before exposure to sevoflurane, halothane, or succinylcholine, people with the abnormal gene are unaffected by the condition and do not experience ill health in relation to the gene. They may still have other health conditions.

However, if a family member is identified as having the causative gene, other family members can undergo genetic testing or muscle biopsy to determine their status. In this way, anaesthetists can be made aware of a patient’s predisposition to an MH crisis, and can make the necessary adjustments, whether that be using a different general anaesthetic or using local and regional anaesthetics where possible.

It may be helpful to explore the diagnostic process of malignant hyperthermia as two scenarios.

Scenario 1: A patient has never been exposed to sevoflurane, dantrolene, or succinylcholine (suxamethonium) and experiences an acute MH crisis:

During the acute, initial presentation of malignant hyperthermia, prompt management of the condition takes priority to prevent fatal complications. Therefore, it is crucial to recognise the signs and symptoms of an acute episode.

However, once the acute phase is managed, the patient can receive a definitive diagnosis after a muscle biopsy or genetic testing. Genetic testing requires a blood test, while a muscle biopsy is more invasive but is the gold-standard diagnostic test.

If a muscle biopsy or genetic testing is positive, then a person is said to be MH susceptible, meaning that they have an increased risk of having an MH episode when exposed to inhaled anaesthetics.

Scenario 2: Patient’s relative experiences an MH crisis:

While the patient is completely healthy and has never experienced any ill health, as their close relative has been identified as being MH-susceptible, it is highly recommended for their close relatives to undergo genetic testing and/or muscle biopsy. Early identification of MH susceptibility can prevent an MH crisis from happening, as the causative agents can be completely avoided in susceptible individuals.

Management and treatment for malignant hyperthermia

The first step in the management of a malignant hyperthermic episode is the cessation of the causative anaesthetic agent.4

Dantrolene sodium is the drug used to treat an acute MH episode. It is administered intravenously (via a vein) as soon as an acute MH crisis is suspected.

It is also important to cool the patient, as well as manage any hyperkalaemia (high potassium in the blood) that occurs because of muscle breakdown.

In future, MH-susceptible individuals should discuss this with their anaesthetist prior to surgery. The anaesthetist can discuss alternative anaesthetic methods, such as regional or local anaesthesia, or alternative general anaesthetics if required. 


If left untreated, an acute episode of malignant hyperthermia can result in death.

An acute episode of malignant hyperthermia can result in several complications, including:4

  • Disseminated intravenous coagulation
  • Congestive heart failure
  • Bowel ischaemia
  • Compartment syndrome
  • Renal failure
  • Rhabdomyolysis
  • Death

In the early days after malignant hyperthermia was initially discovered, the mortality rate was between 70-80%, however, as early diagnosis, treatment, and genetic testing have been implemented further, the rate of death has significantly decreased to less than 5%.5


How common is malignant hyperthermia?

  • 0.002% of people are estimated to be MH-susceptible
  • However, several MS-susceptible individuals will never have an acute episode if they are not exposed to the causative agents5

Who is at risk of developing malignant hyperthermia?

MH-susceptible individuals are at high risk of experiencing an acute episode when exposed to strong inhaled anaesthetics and succinylcholineOne US study demonstrated that ~75% of MH episodes between 1987 and 2006 occurred in people assigned male at birth (AMAB)8

How can I prevent malignant hyperthermia?

  • As a gene is responsible for the syndrome, there is nothing that can be done to prevent someone from being MH-susceptible
  • However, it is possible to prevent an acute episode by avoiding the use of the strong inhaled anaesthetic agents and succinylcholine in people with MH-susceptible relatives or a personal history of acute episodes (both anaesthetic-induced and exertion-induced)
  • Be sure to attend all pre-operative and screening appointments and ensure that your anaesthetist is aware that either you or your relatives are MH-susceptible (if applicable)

When should I see a doctor?

 If you know of a relative who is MH-susceptible or has experienced an acute episode, speak with your doctor about undergoing genetic testing or a muscle biopsy to determine whether you are also susceptible


Malignant hyperthermia is a rare genetic syndrome that only presents when patients are exposed to strong inhaled anaesthetic agents and succinylcholine (suxamethonium). During an acute crisis, there are various different  signs and symptoms, but the key signs are unexplained fast heart rate, fast breathing, and increased temperature. Prompt cessation of the suspected causative agent is key in the management of a crisis, as well as the administration of the drug dantrolene to reduce the chance of death.

If a relative is diagnosed with malignant hyperthermia, speak to your doctor about undergoing genetic testing or muscle biopsy. 


  1. Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015 Mar;96(3):183–95. Available from: https://pubmed.ncbi.nlm.nih.gov/25294644/
  2. Sagui E, Montigon C, Abriat A, Jouvion A, Duron-Martinaud S, Canini F, et al. Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia? PLoS One [Internet]. 2015 Aug 10 [cited 2023 Jul 26];10(8):e0135496. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530942/
  3. Jungbluth H. Central core disease. Orphanet Journal of Rare Diseases [Internet]. 2007 May 15 [cited 2023 Jul 26];2(1):25. Available from: https://doi.org/10.1186/1750-1172-2-25
  4. Rosenberg H, Davis M, James D, Pollock N, Stowell K. Malignant hyperthermia. Orphanet J Rare Dis [Internet]. 2007 Apr 24 [cited 2023 Jul 26];2:21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867813/
  5. Kim DC. Malignant hyperthermia. Korean J Anesthesiol [Internet]. 2012 Nov [cited 2023 Jul 26];63(5):391–401. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506847/
  6. Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, et al. Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists. Anaesthesia [Internet]. 2021 May [cited 2023 Jul 26];76(5):655–64. Available from: https://onlinelibrary.wiley.com/doi/10.1111/anae.15317
  7. Malignant hyperthermia - symptoms, causes, treatment | nord [Internet]. [cited 2023 Jul 26]. Available from: https://rarediseases.org/rare-diseases/malignant-hyperthermia/
  8. Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB. Clinical presentation, treatment, and complications of malignant hyperthermia in north america from 1987 to 2006. Anesthesia & Analgesia [Internet]. 2010 Feb [cited 2023 Jul 26];110(2):498. Available from: https://journals.lww.com/anesthesia-analgesia/Fulltext/2010/02000/Clinical_Presentation,_Treatment,_and.39.aspx
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Grace Olatunde

Student - Bachelor of Medicine, Bachelor of Surgery – MBChB (Medicine) degree, Aston Medical School

Grace is a medical student due to enter her final year of study. She has a passion for patient education and is especially interested in the field of Urology.

She has several years of clinical experience in both public and private sector practice.

She is currently undertaking a PGCert in Health Leadership which she is due to complete in Summer 2024.

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