Abstract
Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disease, triggered by halogenated volatile anesthetics and the depolarizing muscle relaxant succinylcholine. Pediatric intensive care specialists may be confronted with MH in various circumstances: (i) intensive care treatment of a patient presenting with an acute episode of MH, (ii) intensive care treatment of a patient with known MH susceptibility or a suspected history for MH susceptibility, (iii) differential diagnosis of patients presenting with hypermetabolic disorders and/or rhabdomyolysis. Although the triggering mechanisms of MH are not yet fully elucidated, it is well known, that various single point mutations in genes involved in excitation-contraction (EC) coupling of skeletal muscle are causative for MH susceptibility. The most important genetic locus is the RYR1 gene encoding the protein for the calcium channel of the sarcoplasmic reticulum. If MH susceptible individuals are given volatile anesthetics and/or succinylcholine, MH may be triggered. These triggering agents may cause a loss of intracellular calcium control in skeletal muscle, leading to skeletal muscle hypermetabolism, causing metabolic and respiratory acidosis and various consecutive life threatening symptoms if treatment is not initiated immediately. Corner stones of a successful therapy are (i) immediate cessation of triggering agents, (ii) application of dantrolene and (iii) symptomatic treatment of additional clinical and laboratory findings seen during an MH episode. After any clinical MH episode the patient, and in case of a positive finding his or her relatives, must undergo a systematic MH diagnostic workup. Individuals and family members with MH susceptibility should get appropriate information and a warning card for MH. It may be postulated that any loss of myoplasmic calcium control is causing hypermetabolism in various diseases different from MH (e.g. exercise hypermetabolism, heat stroke, sepsis) and thus, similar therapeutic approaches to MH treatment may be applied.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Denborough MA, Lovell RRH. Anaesthetic deaths in a family. Lancet. 1960;II:45.
Denborough MA, Forster JF, Lovell RR, et al. Investigators and Coordinators. Anaesthetic deaths in a family. Br J Anaesth. 1962;34:395–6.
Kalow W, Britt BA, Terreau ME, et al. Investigators and Coordinators. Metabolic error of muscle metabolism after recovery from malignant hyperthermia. Lancet. 1970;2:895–8.
European Malignant Hyperthermia Group. A protocol for the investigation of malignant hyperpyrexia susceptibility. Brit J Anaesth. 1984;56:1267–9.
Larach MG. Standardization of the caffeine halothane muscle contracture test. North American Malignant Hyperthermia Group. Anesth Analg. 1989;69:511–5.
Zorzato F, Fujii J, Otsu K, et al. Investigators and Coordinators. Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1990;265:2244–56.
McCarthy TV, Healy JM, Heffron JJ, et al. Investigators and Coordinators. Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2. Nature. 1990;342:562–4.
Levitt RC, Nourl N, Jedlicka AE, et al. Investigators and Coordinators. Evidence for genetic heterogeneity in malignant hyperthermia susceptibility. Genomics. 1991;11:543–7.
Urwyler A, Deufel T, McCarthy T, et al. Investigators and Coordinators. Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Brit J Anaesth. 2001;86:293–7.
Girard T, Treves S, Voronkov E, et al. Investgators and Coordinators. Molecular genetic testing for malignant hyperthermia susceptibility. Anesthesiology. 2004;100:1076–80.
Levitt RC, Olckers A, Meyers S, et al. Investigators and Coordinators. Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q. Genomics. 1992;14:562–6.
Iles DE, Lehmann-Horn F, Scherer SW, et al. Investigators and Coordinators. Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. Hum Mol Genet. 1994;3:969–75.
Sudbrak R, Procaccio V, Klausnitzer M, et al. Investigators and Coordinators. Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1. Am J Hum Genet. 1995;3:684–91.
European Malignant Hyperthermia Group (EMHG). http://www.emhg.orgaccessed. Accessed 27 Feb 2014.
Hopkins PM. Malignant hyperthermia: pharmacology of triggering. Brit J Anaesth. 2011;107:48–56.
Glahn KP, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010;105:417–20.
iOS application “MHApp” on iTunes. http://itunes.apple.com/app/mhapp/id392766134. Accessed 27 Feb 2014.
iOS application “AnaPaed” on iTunes. http://itunes.apple.com/app/anapaed-kinderanasthesie/id393135847. Accessed 27 Feb 2014.
Davis PJ, Brandom BW. The association of malignant hyperthermia and unusual disease: when you’re hot you’re hot or maybe not. Anesth Analg. 2009;109:1001.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag London
About this chapter
Cite this chapter
Girard, T., Urwyler, A. (2014). Malignant Hyperthermia. In: Wheeler, D., Wong, H., Shanley, T. (eds) Pediatric Critical Care Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-6359-6_8
Download citation
DOI: https://doi.org/10.1007/978-1-4471-6359-6_8
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-6358-9
Online ISBN: 978-1-4471-6359-6
eBook Packages: MedicineMedicine (R0)