Malignant hyperthermia: Causes and Clinical Manifestations


Malignant hyperthermia (MH) is a rare life-threatening genetic hypermetabolic muscle disease, signs and symptoms of which most commonly triggered with exposure to inhaled general anesthetics or succinylcholine. 

 Epidemiology: 1:15,000 in pediatric patients and 1:40,000 adult patients.


Etiology: MH is associated with mutations in two genes: 

  •  RYR1: encodes the skeletal muscle isoform of the calcium-release channel of the sarcoplasmic reticulum; 
  • CACNA1S: encodes the alpha subunit of the L-type calcium channel isoform of the sarcolemma.


Pathophysiology: The sudden release of calcium from sarcoplasmic reticulum removes the inhibition of troponin, resulting in sustained muscle contraction. Markedly increased adenosine triphosphatase activity results in an uncontrolled increase in aerobic and anaerobic metabolism,  increased oxygen consumption and CO2 production, producing severe lactic acidosis and hyperthermia.


Drugs, associated with MH: 


  • Depolarizing muscle relaxants
    • Succinylcholine

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