Malignant hyperthermia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 21 Jun 2025

Last updated: 10 Jan 2025

Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine.

The underlying genetic susceptibility is most often due to a range of autosomal dominant mutations in RYR1.

Caused by an increase in metabolic rate driven by an increase in intracellular calcium levels in muscle.

Presents with increased carbon dioxide production, muscle rigidity, tachycardia, hyperthermia, and mixed metabolic and respiratory acidosis.

A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH.

The mainstay of treatment includes discontinuation of the triggering agent, administration of intravenous dantrolene, and restoration/maintenance of normal core temperature.

Rhabdomyolysis, acute kidney injury, hyperkalemia, and disseminated intravascular coagulation are frequently seen.

If the diagnosis is confirmed, all blood relatives should be contacted since testing for the condition may be indicated.

Definition

Malignant hyperthermia (MH) is a syndrome that typically follows exposure to potent inhalation anesthetics and/or succinylcholine in susceptible individuals.[1][2]Larach MG, Dirksen SJ, Belani KG, et al; Society for Ambulatory Anesthesiology; Malignant Hyperthermia Association of the United States; Ambulatory Surgery Foundation; Society for Academic Emergency Medicine; National Association of Emergency Medical Technicians. Special article: creation of a guide for the transfer of care of the malignant hyperthermia patient from ambulatory surgery centers to receiving hospital facilities. Anesth Analg. 2012 Jan;114(1):94-100. In MH susceptible patients this exposure may produce a clinical MH episode: a dramatic increase in metabolism, which leads to critical temperature elevation and rhabdomyolysis with potential hyperkalemia. In the absence of central core disease, susceptibility to MH is a subclinical condition. However, some MH-susceptible people may feel uncomfortable exercising in the heat, and complaints of muscle cramps are not uncommon.[3]

History and exam

Key diagnostic factors

exposure to potent inhalation anesthetic and/or succinylcholine
susceptibility to MH
previous MH episode
positive family history
increased minute ventilation
elevated core temperature
muscle rigidity

Full details

Other diagnostic factors

tachycardia
decreased urine output
excessive sweating with exercise
muscle cramps
spontaneous episodes of severe muscle stiffness

Full details

Risk factors

exposure to potent inhalation anesthetic and/or succinylcholine
susceptibility to MH
previous MH episode
positive family history
exertional heat illness

Full details

Diagnostic tests

1st tests to order

discontinuation of inhalation anesthetic
exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference)
venous blood gases
serum electrolytes
serum creatinine
therapeutic trial of intravenous dantrolene
creatine kinase
urinalysis
urine myoglobin
platelets
prothrombin time

Full details

Tests to consider

caffeine halothane contracture test (CHCT)
in vitro contracture test (IVCT)
genetic testing
screen for muscle enzyme deficiencies

Full details

Treatment algorithm

ACUTE

inhalation anesthetic-induced

exercise- or heat-induced

Contributors

Authors

Christopher M. Edwards, MD

Assistant Professor

Department of Anesthesiology

University of Florida College of Medicine

Gainesville

Disclosures

CME volunteers for the Malignant Hyperthermia Association of the United States (MHAUS), including as a consultant for the malignant hyperthermia hotline. CME is co-author of a chapter on malignant hyperthermia in Fuhrman & Zimmerman’s Pediatric Critical Care, 6th ed., Elsevier.

Nikolaus Gravenstein, MD

Professor

Department of Anesthesiology

University of Florida College of Medicine

Gainesville

Disclosures

NG is medical adviser/consultant for LifeFlow (410 Medical) and Teleflex, and has received funding from Merck for delivering education lectures to Merck employees. NG is Medical Director of the North American Malignant Hyperthermia Registry.

Acknowledgements

Christopher M Edwards and Nikolaus Gravenstein would like to gratefully acknowledge Dr Barbara W. Brandom and Dr Lena Mayes, the previous contributors to this topic.

Disclosures

LM declares that she has no competing interests. BWB has been reimbursed by the not-for-profit sponsor of the North American MH Registry (NAMHR), the Malignant Hyperthermia Association of the United States (MHAUS) for attending meetings related to the management of the NAMHR. For the past 16 years, BWB received grants from MHAUS to maintain the NAMHR. BWB was the unpaid director of the NAMHR, until Jul 2016. BWB has given lectures and prepared educational materials for her previous employer, the Department of Anesthesiology in the University of Pittsburgh. As of 1 July, 2016, BWB retired from that employment. BWB has published papers and prepared educational materials for MHAUS, with the help of other volunteers for MHAUS. BWB sponsored LM for an award granted by the American Society of Anesthesiologists. This award allowed LM to travel to several medical centers that were active in the diagnosis of MH, as well as to the NAMHR to improve her understanding of this syndrome. This is part of BWB's mentoring of younger anesthesiologists. BWB is also an author of a number of references cited in this topic.

Peer reviewers

Henry Rosenberg, MD

Director

Department of Medical Education and Clinical Research

Saint Barnabas Medical Center

Livingstone

Disclosures

HR declares that he has no competing interests.

Philip Hopkins, MD

Professor of Anesthesia

University of Leeds

Academic Unit of Anesthesia

St James's University Hospital

Leeds

Disclosures

PH is an author of a number of references cited in this topic.

Thierry Girard, MD

Associate Professor

Perioperative Patient Safety

Department of Biomedicine

University Hospital Basel

Basel

Switzerland

Disclosures

TG declares that he has no competing interests.

Joseph Tobin, MD, FAAP, FCCM

Professor and Chairman

Department of Anesthesiology

Wake Forest University School of Medicine

Winston-Salem

Disclosures

JT is an author of a number of references cited in this topic.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Hopkins PM, Girard T, Dalay S, et al. Malignant hyperthermia 2020: guideline from the Association of Anaesthetists. Anaesthesia. 2021 May;76(5):655-64.Full text Abstract

Larach MG, Dirksen SJ, Belani KG, et al; Society for Ambulatory Anesthesiology; Malignant Hyperthermia Association of the United States; Ambulatory Surgery Foundation; Society for Academic Emergency Medicine; National Association of Emergency Medical Technicians. Special article: creation of a guide for the transfer of care of the malignant hyperthermia patient from ambulatory surgery centers to receiving hospital facilities. Anesth Analg. 2012 Jan;114(1):94-100.Full text Abstract

Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict MH susceptibility. Anesthesiology. 1994 Apr;80(4):771-9. Abstract

Hopkins PM, Rüffert H, Snoeck MM, et al. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth. 2015 Oct;115(4):531-9.Full text Abstract

Rüffert H, Bastian B, Bendixen D, et al. Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group. Br J Anaesth. 2021 Jan;126(1):120-30.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Non-MH rhabdomyolysis
- Muscle disuse atrophy
- Myotonia
More Differentials
Guidelines
- Malignant hyperthermia 2020
- Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group
More Guidelines
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Malignant hyperthermia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

inhalation anesthetic-induced

exercise- or heat-induced

Contributors

Authors

Christopher M. Edwards, MD

Disclosures

Nikolaus Gravenstein, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Henry Rosenberg, MD

Disclosures

Philip Hopkins, MD

Disclosures

Thierry Girard, MD

Disclosures

Joseph Tobin, MD, FAAP, FCCM

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice