Real Evidence and Misconceptions about Malignant Hyperthermia in Children: A Narrative Review

Abstract

Malignant hyperthermia is a rare but life-threatening pharmacogenetic disorder triggered by exposure to specific anesthetic agents. Although this occurrence could affect virtually any patient during the perioperative time, the pediatric population is particularly vulnerable, and it has a five-fold higher incidence in children compared to adults. In the last few decades, synergistic efforts among leading anesthesiology, pediatrics, and neurology associations have produced new evidence concerning the diagnostic pathway, avoiding unnecessary testing and limiting false diagnoses. However, a personalized approach and an effective prevention policy focused on clearly recognizing the high-risk population, defining perioperative trigger-free hospitalization, and rapid activation of supportive therapy should be improved. Based on epidemiological data, many national scientific societies have produced consistent guidelines, but many misconceptions are common among physicians and healthcare workers. This review shall consider all these aspects and summarize the most recent updates.

Remimazolam-based total intravenous anesthesia in a patient with a confirmed diagnosis of malignant hyperthermia: a case report

“…MH is an autosomal-dominant genetic disease of RYR1 , and CACNA1S encodes the subunit alpha1 S of Cav1.1. DNA screening, muscle contracture testing, or both are recommended as first-line diagnostic tests for patients with suspected MH [ 3 ]. DNA analyses of peripheral venous blood samples are less invasive than muscle contracture tests that require muscle biopsy, but the probability of detecting disease-causing variants is low, at 30 to 50% [ 16 ].…”

“…DNA analyses of peripheral venous blood samples are less invasive than muscle contracture tests that require muscle biopsy, but the probability of detecting disease-causing variants is low, at 30 to 50% [ 16 ]. RYR1 and CACNA1S variants are associated with MH and diverse forms of congenital myopathy [ 3 ]. In addition, among the over 400 reported RYR1 variants linked to MH [ 16 ], only those with a gain in calcium release function (increased sensitivity to RYR1 agonists) are pathogenic [ 2 , 16 , 17 ].…”

“…The variant curation expert panel of ACMG/AMP reported that RYR1 variants classified as pathologic and likely pathogenic comprised a quarter of the 335 MH-related variants, and two-thirds were classified as variants of uncertain significance (VUS) [ 2 ]. Despite negative DNA test results, predisposition cannot be ruled out [ 2 , 3 , 16 ]. Therefore, testing with muscle biopsy is the next step in diagnosis [ 3 ].…”

“…Despite negative DNA test results, predisposition cannot be ruled out [ 2 , 3 , 16 ]. Therefore, testing with muscle biopsy is the next step in diagnosis [ 3 ]. If variants suspected to be associated with MH are found and considered variants of VUS, further study of the Ca 2+ -regulating function of these variants is needed [ 2 , 16 , 17 ].…”

“…Malignant hyperthermia (MH) is a rare, life-threatening, and pharmacogenetic disorder precipitated by the administration of halogenated volatile anesthetics, such as sevoflurane or desflurane and the depolarizing muscle relaxant succinylcholine [ 1 – 3 ]. MH crisis manifests as a hypermetabolic reaction triggered by an uncontrolled surge in calcium levels within skeletal muscle cells induced by these agents.…”