Pre-Operative Exercise and Pyrexia as Modifying Factors in Malignant Hyperthermia

Background:  Malignant Hyperthermia (MH) is a life-threatening reaction triggered by volatile anaesthetics and succinylcholine characterized by hypercapnia, hypermetabolism and muscle breakdown. MH is most commonly caused by mutations in the skeletal muscle ryanodine receptor  (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between risk genotypes and actual MH incidence remains unexplained. We hypothesized that MH is a compound event, reflecting a synergistic effect of predisposing genotype, triggering anaesthetic, and exercise and/or pyrexia as modifying factors.   Methods:  We performed a retrospective study and identified 41 patients with a history of exercise and/or pyrexia within 72 hours prior to an MH event. We compared the frequency of a history of exercise and/or pyrexia within 72 hours of the triggering agent in “eventful anaesthesias” (n=41) and in “uneventful anaesthesias” (n=51) in the index cases and/or their MH susceptible relatives. Indications for and urgency of surgery, and use of succinylcholine were also recorded.    Findings:  In eventful anaesthesias, there was a history of exercise and/or pyrexia within 72 hours prior to the anaesthetic in 24(0) and 21(1) patients, compared to 0 and 1 in uneventful anesthesias. Trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with eventful anaesthesias.   Interpretation: Exercise and/or pyrexia prior to general anaesthesia are risk factors for MH. Rhabdomyolysis may mimic an acute abdomen, whilst trauma surgery may carry a specific risk due to muscle damage. These observations should inform perioperative guidelines with the potential to reduce fatal anaesthesia complications. Funding Statement: This work is not funded. Declaration of Interests: Sheila Riazi, Luuk van den Bersselaar, Gunilla Islander, Luc Heytens, Marc M. J. Snoeck, Andrew Bjorksten, Robyn Gillies, George Dranitsaris, Anna Hellblom, Susan Treves, Nicol C. Voermans, Heinz Jungbluth: These authors declare no financial interests. Ethics Approval Statement: The retrospective case study was performed with Research Ethics Board approval from the University of Toronto (REB Nr 19-5365), and in accordance with the ethics guidelines issued by other participating centres.