Authors' recommendations: Malignant hyperthermia (MH) or malignant hyperpyrexia is a rare but severe disorder that occurs when patients undergoing anesthesia experience a hyperthermic reaction when exposed to certain anesthetic agents. Anesthetic agents that may trigger MH are desflurane, enflurane, halothane, isoflurane, sevoflurane, and suxamethonium chloride. MH usually occurs in the operating theater, but can occur at anytime during anesthesia and up to an hour after discontinuation. The incidence of MH has been estimated at 1 in 50,000 adults undergoing anesthesia. MH is a disorder of skeletal muscle regulation and clinical signs of MH include metabolic, cardiovascular, and muscular signs. When it was first recognized in the 1960s, mortality from MH was as high as 70%. However, early diagnosis and rapid treatment of MH reduces clinical symptoms and mortality. Treatment of MH consists of immediate withdrawal of anesthesia, administration of dantrolene, and treatment of other symptoms. MH is a pharmacogenetic disorder as sequence variants in the ryanodine receptor 1 (skeletal) (RYR1) gene have been shown to be associated with MH susceptibility (MHS) and are found in up to 80% of patients with confirmed MH, usually with an autosomal dominant pattern of inheritance. RYR1 is a large gene with 106 exons and 5038 amino acids. Although additional genetic loci have been associated with MH, the contribution of these other loci to MH is low. In 2003, the European Malignant Hyperthermia Group (EMHG) established criteria to define RYR1 gene variants that are considered causative for MH. If a RYR1 variant was found in two or more families and functional studies confirmed the pathogenicity of the variant, then it was considered causative for MH. To date, 30 RYR1 sequence variants out of more than 200 RYR1 variants reported have met these criteria and can be considered to be definitely pathogenic for MH. The reference standard test for establishing a clinical diagnosis of MHS is the caffeine halothane contracture test (CHCT) in the United States, and the in vitro contracture test (IVCT) in Europe and Australasia. The CHCT and IVCT are similar and measure the muscle contracture in the presence of the anesthetic halothane and caffeine. Both tests categorize patients as being MHS, MH equivocal (MHE), or MH negative (MHN). These tests are invasive and must be performed using a skeletal muscle biopsy that is < 5 hours old. The cost of performing the CHCT test ranges from $6000 to $10,000 in the United States.

Project Status: Completed

Year Published: 2012

URL for published report: The report may be purchased from:http://www.hayesinc.com/hayes/crd/?crd=13815

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2012 Winifred S. Hayes, Inc