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Susceptibility to malignant hyperthermia: Evaluation and management

Ronald S Litman, DO
Section Editor
Stephanie B Jones, MD
Deputy Editor
Marianna Crowley, MD


Malignant hyperthermia (MH) is a complex genetic disorder of skeletal muscle typically manifesting clinically as a hypermetabolic crisis when a susceptible individual receives a halogenated inhalational anesthetic agent or succinylcholine [1-3]. Patients who are susceptible to MH have skeletal muscle receptor abnormalities that allow excessive myoplasmic calcium to accumulate in the presence of certain anesthetic triggering agents. Very little is known about the specific mechanisms by which anesthetics interact with these abnormal receptors to trigger an MH crisis [4-6].

Susceptibility to MH (MHS) may arise de novo or be inherited in an autosomal dominant fashion. It is suspected in individuals with a history of a clinical event strongly suspicious for an acute MH crisis or with a family history of susceptibility. The mainstay of prevention is the identification of these genetically susceptible individuals. Avoidance of anesthetic triggers in MHS patients and prompt administration of dantrolene when an acute event occurs have reduced the mortality associated with malignant hyperthermia from historic rates of 70 percent to <1 percent [7,8].

This topic will review the genetic basis and testing for MHS and the safe administration of anesthesia to MHS patients. The pathophysiology, clinical manifestations, diagnosis, and management of an acute MH crisis are discussed elsewhere. (See "Malignant hyperthermia: Clinical diagnosis and management of acute crisis".)


The prevalence of susceptibility to malignant hyperthermia (MHS) in the general population is unknown, though it is estimated at 1:2000 by the Malignant Hyperthermia Association of the United States [9]. Published rates of susceptibility vary widely depending upon the population studied and the manner in which MHS was determined. Prevalence is most often studied in family cohorts of patients known to be MHS; rates range from 1:200 to 1:5000 in these cohorts [10,11]. Incomplete penetrance and variable expressivity lead to far fewer cases of clinically significant MH than gene prevalence rates would suggest.


Susceptibility to malignant hyperthermia (MHS) is conferred by mutations of genes associated with proteins controlling levels of cytosolic calcium and, therefore, skeletal muscle contraction [12]. Approximately one-half of cases are inherited in an autosomal dominant fashion; others are presumed to be new mutations. Genes responsible for coding proteins of the calcium channel in the sarcoplasmic reticulum are most commonly affected: the ryanodine receptor (RYR1) and the closely associated dihydropyridine receptor (DHP). The likelihood that a susceptible patient will develop MH depends upon the specific type of receptor mutation [13]. Because of incomplete genetic penetrance and variable expressivity, there is great variability in the clinical expression of the syndrome among individuals and between anesthetic episodes in the same individual [14,15]. (See "Malignant hyperthermia: Clinical diagnosis and management of acute crisis", section on 'Clinical presentation'.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 10, 2017.
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