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Malignant hyperthermia

Last updated: February 24, 2021

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Malignant hyperthermia (MH) is a subclinical myopathy in which general anesthesia triggers an uncontrollable contraction of skeletal muscle that leads to a life-threatening hypercatabolic state and increase in body temperature. The disease is primarily autosomal dominant; mutations in receptors (especially ryanodine receptor type 1) predispose to volatile anesthetic agents or succinylcholine causing an accumulation of intracellular calcium in skeletal muscle that leads to its overactivation and hypermetabolism. In the acute setting, diagnosis is based mainly on clinical presentation and end-tidal capnography, which reveals an increase in end-tidal CO2. Immediate treatment measures involve stopping the triggering agent and administration of dantrolene. In nonacute settings, there are specific diagnostic tools (e.g., caffeine halothane contracture test) to confirm suspected cases. MH is a lethal disease and has a high mortality rate if left untreated.


Epidemiological data refers to the US, unless otherwise specified.


Administration of triggering substances → calcium release from intercellular compartments or delay in its reuptake → ↑ calcium in muscle cells → ↑ contractility of the skeletal muscle → ↑ metabolism → ↑ oxygen consumption in addition to ↑ CO2 production, heat, and lactate (malignant hyperthermia) → mixed respiratory and metabolic acidosis uncoupled oxidative phosphorylation breakdown of the cell's energy supply → cell death

Smooth muscle and cardiac muscle remain unaffected!


Although the rise in body temperature is usually a late sign in malignant hyperthermia, it may occur as an early sign in severe cases!


The diagnosis is based on clinical presentation (e.g., muscle and jaw rigidity, hyperthermia) with an increase in end-tidal CO2 and signs of muscle breakdown. Confirmatory tests are reserved for stabilized patients and to prophylactically investigate those with a positive family history.

References [1]

The differential diagnoses listed here are not exhaustive.

Dantrolene directly deals with distressed muscle.

If adequately treated, the mortality rate is < 10%. In the absence of rapid, appropriate treatment, the mortality rate is ∼ 70%.

  1. Litman RS. Malignant hyperthermia: Clinical diagnosis and management of acute crisis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: September 1, 2016. Accessed: December 30, 2016.
  2. Chapin JW. Malignant Hyperthermia. In: Geibel J, Malignant Hyperthermia. New York, NY: WebMD. Updated: December 22, 2016. Accessed: December 30, 2016.
  3. Murray MJ, Harrison BA, Mueller JT, Rose SH, Wass CT, Wedel DJ. Faust's Anesthesiology Review. Elsevier Health Sciences ; 2014
  4. What evidence-based interventions are recommended to alleviate hyperthermia associated with Malignant Hyperthermia?. . Accessed: February 18, 2021.