Investigations on the Relationship Between the Autonomic Nervous System and the Triggering of Malignant Hyperthermia: A State-of-the-Science Review

Abstract

Early research in malignant hyperthermia (MH) focused on the autonomic nervous system (ANS) as a primary trigger of the syndrome. This hypothesis was based on the initial signs and symptoms of MH such as tachycardia, cardiac arrhythmias, hypertension, and signs of increased metabolism in patients who developed MH. Supporting these early links between MH and the ANS were case reports from anesthesia providers who reported that patients who subsequently developed MH after a nontriggering previous anesthetic had appeared unusually stressed prior to the surgical procedure in which they triggered. There is no disagreement in the scientific community that a primary disorder in MH lies in the inability to control myoplasmic calcium levels in skeletal muscles. However, considering the variability in genetic and clinical presentation, the timing of intraoperative triggering, and the unexplained phenomenon of nonanesthetic triggering, the identification of cofactors in MH triggering remains paramount. A careful review of existing research supports the hypothesis that the autonomic nervous system plays a significant role as a cofactor in the triggering and progression of an MH episode. If a differentiation can be made and a link can be demonstrated between abnormalities in receptor sensitivity for or release, reuptake, or metabolism of catecholamines in malignant hyperthermia susceptible individuals, we may be able to use these as additional markers/predictors of disease.