Malignant hyperthermia (MH) is an uncommon inherited, potentially lethal pharmacogenetic disorder of the skeletal muscle, which is triggered by all volatile anaesthetics (such as isoflurane, sevoflurane, halothane and desflurane) and/or depolarising muscle relaxants (i.e. succinylcholine). Furthermore, in rare cases MH syndrome can also be triggered by strenuous physical exercise and/or heat exposure.
The clinical incidence of MH seems to be low and ranges between 1 : 5,000 and 1 : 100,000. However, the frequency has increased in the recent years and the in-hospital-mortality from MH is even today elevated and higher than previously calculated (up to 12 % of all MH cases). Additionally, due to the autosomal dominant inheritance in humans, the prevalence can be estimated up to 1 : 3,000.
Malignant hyperthermia (MH) is an uncommon inherited, potentially lethal pharmacogenetic disorder of the skeletal muscle, which is triggered by all volatile anaesthetics (such as isoflurane, sevoflurane, halothane and desflurane) and/or depolarising muscle relaxants (i.e. succinylcholine). Furthermore, in rare cases MH syndrome can also be triggered by strenuous physical exercise and/or heat exposure.
The clinical incidence of MH seems to be low and ranges between 1 : 5,000 and 1 : 100,000. However, the frequency has increased in the recent years and the in-hospital-mortality from MH is even today elevated and higher than previously calculated (up to 12 % of all MH cases). Additionally, due to the autosomal dominant inheritance in humans, the prevalence can be estimated up to 1 : 3,000.
MH is caused by an abnormal regulation of calcium metabolism within the skeletal muscle cell, most probably due to a defective calcium release channel or so-called ryanodine receptor (RYR1) at the sarcoplasmic reticulum (SR). Once MH is triggered a rapid and uncontrolled release of calcium from the SR into the myoplasm is initiated. This results in a hypermetabolic state, leading to the typical clinical signs such as tachycardia, muscle rigidity, hypercapnia, rhabdomyolysis, hypoxaemia and the name-giving hyperthermia.
The human skeletal muscle ryanodine receptor is coded at the q13.1-13.2 region on chromosome 19. Moleculargenetic studies revealed that in up to 70% of the families with a disposition to MH the ryanodine receptor locus is coupled to the MH phenotype. To date, more than 300 RYR1 variants that cosegregate with MH and/or Central Core Disease have been reported. Furthermore, five other loci have been identified by linkage analysis, and mutations in the CACN1AS gene, encoding the main subunit of the dihydropyridine receptor, have been found on chromosome 1. However, it is not known how many of them are really causative for MH. A list of actually proven causative mutations is published on the homepage of the European MH Group (www.emhg.org).
Treatment of MH crisis consists of symptomatic as well as specific measures with the antidote dantrolene in accordance to the guidelines of anaesthesiological societies. Anaesthesia in patients with suscpetibility to MH can be performed under safe conditions with a decontaminated anaesthesia machine, avoidance of trigger substances and immediate availability of dantrolene.