Malignant hyperthermia

Last updated: December 1, 2021

Summarytoggle arrow icon

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 an 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.

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Administration of triggering substances → calcium release from intracellular 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.

Clinical featurestoggle arrow icon

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

Diagnosticstoggle arrow icon

Diagnosis is generally clinical, based on intraoperative signs and symptoms (e.g., muscle and jaw rigidity, hyperthermia) in connection with increased end-tidal CO2 and signs of muscle breakdown. Patients with a positive family history, suspicious clinical history, or masseter muscle rigidity should receive confirmatory preoperative testing to rule out the risk of MH.

Preoperative diagnostics [2]

  • Gold standard: caffeine-halothane contracture test (CHCT)
    • A muscle sample is obtained under regional anesthesia.
    • The muscle sample is divided with the grain of the fibers into six strips.
    • After tissue viability testing via electrical stimulation, the muscle strips are mounted into a bath.
    • Three strips are exposed to 3% halothane, and the remaining three other strips are exposed to caffeine.
    • The test is considered positive if any of the strips contract.
    • Disadvantages: only available at select testing centers, which will likely require the patient to travel.
  • Molecular genetic testing: low sensitivity, but highly specific and less expensive and invasive than CHCT

Intraoperative diagnostics

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

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%.

Referencestoggle arrow icon

  1. Murray MJ, Harrison BA, Mueller JT, Rose SH, Wass CT, Wedel DJ. Faust's Anesthesiology Review. Elsevier Health Sciences ; 2014
  2. Rosenberg H, Antognini JF, Muldoon S. Testing for Malignant Hyperthermia. Anesthesiology. 2002; 96 (1): p.232-237.doi: 10.1097/00000542-200201000-00036 . | Open in Read by QxMD
  3. What evidence-based interventions are recommended to alleviate hyperthermia associated with Malignant Hyperthermia?. . Accessed: February 18, 2021.

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