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Malignant Hyperthermia: Treatment

Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic syndrome triggered by halogenated volatile anesthetic gases and succinylcholine. Most patients with MH have abnormal Ryanodine receptors (RYR1). Under normal circumstances, RYR1 facilitates the release of calcium from the sarcoplasmic reticulum into the cytosol during action potential propagation, leading to muscle contraction. During MH, the triggering agents induce prolonged opening of abnormal RYR1 receptors, leading an uncontrolled release of calcium from the sarcoplasmic reticulum unto persistent muscle contraction and rigidity. Classically, it presents as a hypermetabolic syndrome featuring hypercarbia (ETCO2 > 55 mmHg or arterial PaCO2 > 60 mmHg; often the first presenting sign), masseter muscle rigidity, generalized muscle rigidity, and hyperthermia (a later finding). Though its low incidence (1:100,000) and highly-variable presentation make diagnosing MH quite difficult, clinicians must recognize and treat MH rapidly due to its brisk symptom progression and high mortality (approximately 1% of all deaths under anesthesia).

Once acute MH is suspected (hypercarbia not resolving to hyperventilation, generalized rigidity, PVCs, tachycardia, unstable arterial pressure, masseter spasm, unexplained metabolic acidosis), the MH Protocol should be initiated. The Malignant Hyperthermia Association of the United States (MHAUS) identifies the following actions that the anesthesiologist should immediately take:

  1. Notify the surgical team to immediately stop the procedure, if possible
  2. Discontinue any MH-triggering agents. If the procedure cannot be aborted, switch to IV non-triggering anesthetics (IV sedatives, narcotics, amnesiacs, and non-depolarizing neuromuscular blockers)
  3. Call for additional personnel and dantrolene/MH cart. If at a ambulatory surgical center, 911 should be notified. An anesthesiology team member should contact MHAUS HOTLINE (1-800-644-9737) for additional diagnostic and treatment advise
  4. Hyperventilate with 100% oxygen at flows of 10L/min to flush volatile anesthetics and lower ETCO2. If available, insert activated charcoal filters into the inspiratory and expiratory limbs of the breathing circuit, replacing hourly with additional activated charcoal filters for the duration of the procedure.
  5. Give IV dantrolene (2.5 mg/kg rapidly through large-bore IV, repeating as frequently as needed until the patient responds with a decreased in ETCO2, decreased muscle rigidity, and/or lower heart rate.

After completing these steps, further management is guided by the persistence of hypercarbia, the degree of acidosis present, any electrolyte abnormalities, urine output, coagulation studies, and other tests as indicated. Vital signs, core temperature, ETCO2, minute ventilation, blood gases, electrolytes, CK, urine myoglobin, and coagulation studies as warranted by the clinical severity of the patient should be followed. Sodium bicarbonate should be considered for severe metabolic acidosis, especially for base excesses greater then -8. Active cooling should be initiated for patient core temperatures > 39°C and stopped once < 38°C. Hyperkalemia should be treated aggressively with calcium chloride and sodium bicarbonate (or ECMO if cardiac arrest occurs). Dysrhythmias should be treated with standard antiarrhythmics, but calcium channel blockers should be avoided. Diuretics should be titrated to > 1 mL/kg/hr urine output. Once the patient is stable, he or she should be transferred to the ICU for at least 24 hours to further assess, evaluate, and/or treat hypercarbia, dysrhythmias, hyperthermia, and generalized muscular rigidity.


  1. Schneiderbanger D, Johannsen S, Roewer N, Schuster F. Management of malignant hyperthermia: diagnosis and treatment. Ther Clin Risk Manag. 2014;10:355–362. Published 2014 May 14. doi:10.2147/TCRM.S47632 PubMed Link
  2. Ronald S. Litman, Sarah M. Griggs, James J. Dowling, Sheila Riazi; Malignant Hyperthermia Susceptibility and Related Diseases. Anesthesiology 2018;128(1):159-167. PubMed Link

Other References

  1. Litman R, Jones S, Crowley M. Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. (Accessed on May 09, 2019.) Link
  2. Recommendation for Temperature Monitoring during General Anesthesia (accessed 5/28/2019) Link