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Malignant hyperthermia of anesthesia

MedGen UID:
9867
Concept ID:
C0024591
Pathologic Function
Synonym: Hyperthermia of anesthesia
SNOMED CT: Malignant hyperpyrexia due to anesthesia (213026003); Malignant hyperthermia due to anesthesia (213026003); Malignant hyperpyrexia due to anesthetic (213026003); Malignant hyperthermia caused by anesthesia (213026003); Malignant hyperpyrexia caused by anesthesia (213026003); Malignant hyperpyrexia caused by anesthetic (213026003)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Monarch Initiative: MONDO:0018493
OMIM®: 145600
Orphanet: ORPHA423

Disease characteristics

Excerpted from the GeneReview: Malignant Hyperthermia Susceptibility
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. [from GeneReviews]
Authors:
Henry Rosenberg  |  Nyamkhishig Sambuughin  |  Sheila Riazi, et. al.   view full author information

Additional description

From PharmGKB
Malignant hyperthermia susceptibility (MHS) is a predisposition to a potentially life-threatening, hypermetabolic reaction triggered by potent volatile anesthetics (i.e. desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane) or the depolarizing muscle relaxant succinylcholine. These agents are relatively contraindicated in persons with MHS. MHS is diagnosed either by a positive response to the in vitro contracture test (IVCT) or the caffeine-halothane contracture test (CHCT), or by the presence of a pathogenic variant in RYR1 or CACNA1S that has been identified as causative for MHS (PMID: 30499100). Absence of pathogenetic variants in RYR1 or CACNA1S does not eliminate the chance of MHS based on findings that the genetic cause remains unknown for about half of all MH survivors, with contracture test-confirmed MHS (PMID: 28902675). Both genes are included on the list of actionable secondary findings by the American College of Medical Genetics and Genomics. MHS is inherited in an autosomal dominant manner and a positive result for a patient has familial ramifications. In addition to potential variations in RYR1 or CACNA1S, personal or family history of a reaction to these drugs or agents needs to be considered. Therapeutic guidelines for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).  https://www.pharmgkb.org/guidelineAnnotation/PA166180457

Professional guidelines

PubMed

Johnston JJ, Dirksen RT, Girard T, Hopkins PM, Kraeva N, Ognoon M, Radenbaugh KB, Riazi S, Robinson RL, Saddic Iii LA, Sambuughin N, Saxena R, Shepherd S, Stowell K, Weber J, Yoo S, Rosenberg H, Biesecker LG
Hum Mol Genet 2022 Nov 28;31(23):4087-4093. doi: 10.1093/hmg/ddac145. PMID: 35849058Free PMC Article
Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Rüffert H, Bastian B, Bendixen D, Girard T, Heiderich S, Hellblom A, Hopkins PM, Johannsen S, Snoeck MM, Urwyler A, Glahn KPE; European Malignant Hyperthermia Group
Br J Anaesth 2021 Jan;126(1):120-130. Epub 2020 Oct 31 doi: 10.1016/j.bja.2020.09.029. PMID: 33131754

Curated

Orphanet Emergency Guidelines: Malignant hyperthermia

Suggested Reading

PubMed

Sei Y, Sambuughin N, Muldoon S
Anesthesiology 2004 Feb;100(2):464-5. doi: 10.1097/00000542-200402000-00058. PMID: 14870754

Recent clinical studies

Etiology

Johnston JJ, Dirksen RT, Girard T, Hopkins PM, Kraeva N, Ognoon M, Radenbaugh KB, Riazi S, Robinson RL, Saddic Iii LA, Sambuughin N, Saxena R, Shepherd S, Stowell K, Weber J, Yoo S, Rosenberg H, Biesecker LG
Hum Mol Genet 2022 Nov 28;31(23):4087-4093. doi: 10.1093/hmg/ddac145. PMID: 35849058Free PMC Article
Lott C, Truhlář A, Alfonzo A, Barelli A, González-Salvado V, Hinkelbein J, Nolan JP, Paal P, Perkins GD, Thies KC, Yeung J, Zideman DA, Soar J; ERC Special Circumstances Writing Group Collaborators
Resuscitation 2021 Apr;161:152-219. Epub 2021 Mar 24 doi: 10.1016/j.resuscitation.2021.02.011. PMID: 33773826
Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Baldo BA, Rose MA
Br J Anaesth 2020 Jan;124(1):44-62. Epub 2019 Oct 22 doi: 10.1016/j.bja.2019.08.010. PMID: 31653394
Patton K, Borshoff DC
Anaesthesia 2018 Jan;73 Suppl 1:76-84. doi: 10.1111/anae.14143. PMID: 29313907

Diagnosis

Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Kaur H, Katyal N, Yelam A, Kumar K, Srivastava H, Govindarajan R
Mo Med 2019 Mar-Apr;116(2):154-159. PMID: 31040503Free PMC Article
Hopkins PM, Gupta PK, Bilmen JG
Handb Clin Neurol 2018;157:645-661. doi: 10.1016/B978-0-444-64074-1.00038-0. PMID: 30459030
Sessler DI
Lancet 2016 Jun 25;387(10038):2655-2664. Epub 2016 Jan 8 doi: 10.1016/S0140-6736(15)00981-2. PMID: 26775126
Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K
Orphanet J Rare Dis 2015 Aug 4;10:93. doi: 10.1186/s13023-015-0310-1. PMID: 26238698Free PMC Article

Therapy

Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Kaur H, Katyal N, Yelam A, Kumar K, Srivastava H, Govindarajan R
Mo Med 2019 Mar-Apr;116(2):154-159. PMID: 31040503Free PMC Article
Sessler DI
Lancet 2016 Jun 25;387(10038):2655-2664. Epub 2016 Jan 8 doi: 10.1016/S0140-6736(15)00981-2. PMID: 26775126
Bandschapp O, Girard T
Swiss Med Wkly 2012;142:w13652. Epub 2012 Jul 31 doi: 10.4414/smw.2012.13652. PMID: 22851008
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Prognosis

Kushnir A, Todd JJ, Witherspoon JW, Yuan Q, Reiken S, Lin H, Munce RH, Wajsberg B, Melville Z, Clarke OB, Wedderburn-Pugh K, Wronska A, Razaqyar MS, Chrismer IC, Shelton MO, Mankodi A, Grunseich C, Tarnopolsky MA, Tanji K, Hirano M, Riazi S, Kraeva N, Voermans NC, Gruber A, Allen C, Meilleur KG, Marks AR
Acta Neuropathol 2020 Jun;139(6):1089-1104. Epub 2020 Mar 31 doi: 10.1007/s00401-020-02150-w. PMID: 32236737Free PMC Article
Patton K, Borshoff DC
Anaesthesia 2018 Jan;73 Suppl 1:76-84. doi: 10.1111/anae.14143. PMID: 29313907
Saba R, Kaye AD, Urman RD
Anesthesiol Clin 2017 Jun;35(2):285-294. doi: 10.1016/j.anclin.2017.01.014. PMID: 28526149
Jungbluth H
Orphanet J Rare Dis 2007 May 15;2:25. doi: 10.1186/1750-1172-2-25. PMID: 17504518Free PMC Article
Gronert GA
Anesthesiology 1980 Nov;53(5):395-423. doi: 10.1097/00000542-198011000-00007. PMID: 6999950

Clinical prediction guides

Kushnir A, Todd JJ, Witherspoon JW, Yuan Q, Reiken S, Lin H, Munce RH, Wajsberg B, Melville Z, Clarke OB, Wedderburn-Pugh K, Wronska A, Razaqyar MS, Chrismer IC, Shelton MO, Mankodi A, Grunseich C, Tarnopolsky MA, Tanji K, Hirano M, Riazi S, Kraeva N, Voermans NC, Gruber A, Allen C, Meilleur KG, Marks AR
Acta Neuropathol 2020 Jun;139(6):1089-1104. Epub 2020 Mar 31 doi: 10.1007/s00401-020-02150-w. PMID: 32236737Free PMC Article
Saba R, Kaye AD, Urman RD
Anesthesiol Clin 2017 Jun;35(2):285-294. doi: 10.1016/j.anclin.2017.01.014. PMID: 28526149
Davis PJ, Brandom BW
Anesth Analg 2009 Oct;109(4):1001-3. doi: 10.1213/ane.0b013e3181b493d4. PMID: 19762721
Ording H
Ann Fr Anesth Reanim 1989;8(5):411-6. doi: 10.1016/S0750-7658(89)80007-3. PMID: 2697155
Gronert GA
Anesthesiology 1980 Nov;53(5):395-423. doi: 10.1097/00000542-198011000-00007. PMID: 6999950

Recent systematic reviews

Larach MG, Klumpner TT, Brandom BW, Vaughn MT, Belani KG, Herlich A, Kim TW, Limoncelli J, Riazi S, Sivak EL, Capacchione J, Mashman D, Kheterpal S, Kooij F, Wilczak J, Soto R, Berris J, Price Z, Lins S, Coles P, Harris JM, Cummings KC 3rd, Berman MF, Nanamori M, Adelman BT, Wedeven C, LaGorio J, McCormick PJ, Tom S, Aziz MF, Coffman T, Ellis TA 2nd, Molina S, Peterson W, Mackey SC, van Klei WA, Ginde AA, Biggs DA, Neuman MD, Craft RM, Pace NL, Paganelli WC, Durieux ME, Nair BJ, Wanderer JP, Miller SA, Helsten DL, Turnbull ZA, Schonberger RB; Multicenter Perioperative Outcomes Group
Anesthesiology 2019 Jan;130(1):41-54. doi: 10.1097/ALN.0000000000002490. PMID: 30550426
Kraeva N, Sapa A, Dowling JJ, Riazi S
Can J Anaesth 2017 Jul;64(7):736-743. Epub 2017 Mar 21 doi: 10.1007/s12630-017-0865-5. PMID: 28326467
Wass CT, Warner ME, Worrell GA, Castagno JA, Howe M, Kerber KA, Palzkill JM, Schroeder DR, Cascino GD
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J Thorac Cardiovasc Surg 2011 Jun;141(6):1488-95. Epub 2011 Mar 3 doi: 10.1016/j.jtcvs.2011.01.034. PMID: 21376345

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