European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility

Abstract

It is 30 yr since the British Journal of Anaesthesia published the first consensus protocol for the laboratory diagnosis of malignant hyperthermia susceptibility from the European Malignant Hyperthermia Group. This has subsequently been used in more than 10 000 individuals worldwide to inform use of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and guidelines, and new sections, including recommendations for patient referral criteria and clinical interpretation of laboratory findings.

Hipertermia maligna. Aspectos históricos

“…El mapeo genético de la enfermedad condujo a desarrollar test diagnósticos que identificaran estas mutaciones 37 . Estas determinaciones se hicieron realidad con el advenimiento del tercer milenio.…”

“…Se pensó que estos métodos diagnósticos con análisis de ADN iban a constituir un modo más eficiente y menos invasivo de screening que reemplazaría al IVCT. El problema está en que sólo 50-70% de los casos de hipertermia maligna se asocian a mutación del mencionado gen. Este grado de heterogeneidad ha redundado en que el tradicional IVCT no ha sido suplantado como Gold standard 37 .…”

PharmGKB summary

“…According to the MHAUS, diagnostic testing for MHS is not recommended as a screening tool, and should only be undertaken after the detailed medical and family history of a patient suggests that he or she may be MHS, particularly if that patient is awaiting surgery. Typically, patients with a previous episode of suspected, or confirmed MH in the presence of trigger agents, or with a family history of MHS are good candidates for diagnostic testing [73, 74]. The two diagnostic test options for MHS are the in vitro contracture test (IVCT, or caffeine halothane contracture test in the U.S) or a genetic test of RYR1 and CACNA1S .…”

“…If the force of contracture is ≥ to 2 mN when tested with halothane and caffeine the diagnosis is MHShc, but if the force of contracture is ≥ 2 mN with either halothane, or caffeine, but not both, the diagnosis is MHSh, or MHSc, respectively. The term MH equivocal for patients that were sensitive to either caffeine or halothane was recently changed to MHSh or MHSc for halothane, or caffeine [73]. A major limitation of the IVCT/CHCT is that specialized testing centers are scarce.…”

“…The EMHG guideline recommends that the decision to pursue genetic testing or IVCT first be considered on a case-by-case basis and should include input from the MH diagnostic center, the physician, and patient. Test availability and turnaround time, as well whether a patient is awaiting surgery should be considered when making the decision [73]. The revised EMHG guidelines also consider “potentially MHS-associated” variants as increasing an individual’s risk of MHS until IVCT can be performed.…”