Malignant hyperthermia: Brazilian multidisciplinary study

Abstract

Malignant hyperthermia (MH) is a pharmacogenetic skeletal muscle disease expressed as a hypermetabolic response to volatile anesthetics and/or the depolarizing muscle relaxant succinylcholine and, rarely, to intense physical exercise and ambient heat. Genes linked to the excitation-muscle contraction process are involved, especially the ryanodine receptor 1 gene RYR1. In genetically susceptible patients, exposure to triggers leads to exaggerated / continuous release of calcium by the sarcoplasmic reticulum, with rapid onset of tachycardia, hypercarbia, hyperthermia, muscular rigidity, rhabdomyolysis, lactic acidosis, and multisystemic involvement, with 80% mortality without adequate treatment. The at-risk population comprises a broad spectrum ranging from survivors of MH crisis, their relatives, and patients with some neuromuscular diseases and congenital osteoarticular disorders. The standard method for diagnosing MH susceptibility is the in vitro muscle contracture test (IVCT) in response to halothane and caffeine. Our objectives are 1.To characterize the clinical-radiological-anatomopathological-metabolic-genetics expression of MH in a Brazilian sample, through multidisciplinary approach that includes research on susceptibility with IVCT, osteoarticular/muscle imaging, cardiopulmonary exercise test with cardiac output by transthoracic impedance associated with near-infrared spectroscopy and body composition measurement, muscle pathology, muscle biochemical study, intracellular calcium dynamics, and molecular study for the search of genetic variants. (AU)