Pre-operative exercise and pyrexia as modifying factors in malignant hyperthermia (MH)

• Published in: Neuromuscular disorders : NMD Vol. 32; no. 8; pp. 628 - 634
• Main Authors: Riazi, Sheila, Bersselaar, Luuk R. van den, Islander, Gunilla, Heytens, Luc, Snoeck, Marc M.J., Bjorksten, Andrew, Gillies, Robyn, Dranitsaris, George, Hellblom, Anna, Treves, Susan, Kunst, Gudrun, Voermans, Nicol C., Jungbluth, Heinz
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022
• Subjects: (Exertional) rhabdomyolysis; Basic Medicine; Malignant hyperthermia; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; RYR1; RYR1; Malignant hyperthermia; (Exertional) rhabdomyolysis
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2022.06.003

•Malignant Hyperthermia (MH) is mainly due to mutations in RYR1.•The discrepancy between the frequency of risk genotypes and of MH events remains unexplained.•Pre-operative exercise or pyrexia may increase MH risk in genetically susceptible individuals. Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle ryanodine receptor (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between the prevalence of risk genotypes and actual MH incidence remains unexplained. We investigated the role of pre-operative exercise and pyrexia as potential MH modifying factors. We included cases from 5 MH referral centers with 1) clinical features suggestive of MH, 2) confirmation of MH susceptibility on Contracture Testing (IVCT or CHCT) and/or RYR1 genetic testing, and a history of 3) strenuous exercise within 72 h and/or pyrexia >37.5 °C prior to the triggering anesthetic. Characteristics of MH-triggering agents, surgery and succinylcholine use were collected. We identified 41 cases with general anesthesias resulting in an MH event (GA+MH, n = 41) within 72 h of strenuous exercise and/or pyrexia. We also identified previous general anesthesias without MH events (GA-MH, n = 51) in the index cases and their MH susceptible relatives. Apart from pre-operative exercise and/or pyrexia, trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with GA+MH events. These observations suggest a link between pre-operative exercise, pyrexia and MH.