What are the characteristics of malignant hyperthermia regarding its induction and relation to potassium metabolism?

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From the Guidelines

Malignant hyperthermia is more common in children than adults, and it is not induced by local anesthetics, nondepolarizing muscle relaxants, or nitrous oxide, but rather by volatile anesthetic gases and the depolarizing muscle relaxant succinylcholine. Malignant hyperthermia is a rare but potentially fatal genetic disorder characterized by a hypermetabolic crisis triggered by certain anesthetic agents 1. The condition occurs more frequently in pediatric patients than adults, with a higher incidence in children and young adults. The highest reported incidence of malignant hyperthermia occurs in pediatric populations, and there is also a consistently higher incidence of malignant hyperthermia reactions in men compared with women 1.

Some key points to consider:

  • Malignant hyperthermia is triggered primarily by volatile anesthetic gases (such as sevoflurane, desflurane, and isoflurane) and the depolarizing muscle relaxant succinylcholine, not by local anesthetics, nondepolarizing muscle relaxants, or nitrous oxide 1.
  • While potassium abnormalities can occur during a malignant hyperthermia crisis, the underlying pathophysiology involves dysregulated calcium release from the sarcoplasmic reticulum in skeletal muscle due to mutations in the ryanodine receptor gene (RYR1) 1.
  • The clinical features of a malignant hyperthermia reaction include increased heart rate, increased body temperature, acidosis, hyperkalaemia, and arrhythmias, and can lead to disseminated intravascular coagulopathy, massive rhabdomyolysis, and acute occlusive renal injury 1.
  • The most crucial recommendation is that malignant hyperthermia-susceptible patients should receive anaesthesia that is free of triggering agents 1.

In terms of the options provided:

  • (a) can be induced by local anesthetics: incorrect, as local anesthetics are not triggering agents for malignant hyperthermia 1.
  • (b) can be induced by nondepolarizing muscle relaxants: incorrect, as nondepolarizing muscle relaxants are not triggering agents for malignant hyperthermia 1.
  • (c) can be induced by nitrous oxide: incorrect, as nitrous oxide is not a triggering agent for malignant hyperthermia 1.
  • (d) is related to disordered K+ metabolism: incorrect, as while potassium abnormalities can occur during a malignant hyperthermia crisis, the underlying pathophysiology involves dysregulated calcium release from the sarcoplasmic reticulum in skeletal muscle due to mutations in the ryanodine receptor gene (RYR1) 1.
  • (e) is more common in children than adults: correct, as malignant hyperthermia occurs more frequently in pediatric patients than adults, with a higher incidence in children and young adults 1.

From the FDA Drug Label

In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In affected humans, it has been postulated that "triggering agents" (e.g., general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. Malignant Hyperthermia Succinylcholine administration has been associated with acute onset of malignant hyperthermia, a potentially fatal hypermetabolic state of skeletal muscle. The risk of developing malignant hyperthermia following succinylcholine administration increases with the concomitant administration of volatile anesthetics

The correct answers are:

  • (b) can be induced by nondepolarizing muscle relaxants: No, the text actually says depolarizing neuromuscular blocking agents.
  • (b) is actually incorrect, but (a) can be induced by local anesthetics: No, the text does not mention local anesthetics as triggering agents.
  • (c) can be induced by nitrous oxide: No, the text mentions volatile anesthetics, but does not specifically mention nitrous oxide.
  • The correct answer is:
    • Malignant hyperthermia can be induced by depolarizing muscle relaxants, such as succinylcholine 2
    • Malignant hyperthermia can be induced by general anesthetics 3
    • There is no information about local anesthetics or nitrous oxide
    • There is no information about disordered K+ metabolism in relation to malignant hyperthermia
    • There is no information about the prevalence of malignant hyperthermia in children versus adults

From the Research

Malignant Hyperthermia Inducing Agents

  • Malignant hyperthermia can be induced by volatile anesthetic gases such as halothane, sevoflurane, desflurane, and isoflurane, as well as the depolarizing muscle relaxant succinylcholine 4, 5, 6, 7.
  • Nondepolarizing muscle relaxants do not trigger malignant hyperthermia 4.
  • Nitrous oxide, intravenous induction agents, benzodiazepines, and opioids do not trigger malignant hyperthermia 4.
  • Local anesthetics are not mentioned as triggering agents in the provided studies.

Demographics and Metabolism

  • Malignant hyperthermia affects both children and adults, but the exact prevalence in different age groups is unknown 6, 8.
  • The syndrome is related to disordered calcium metabolism, not potassium metabolism 5, 6, 7, 8.
  • Hyperkalemia is a clinical sign of malignant hyperthermia, resulting from the uncontrolled rise of myoplasmic calcium and subsequent muscle damage 5, 6, 7.

Prevalence and Inheritance

  • The incidence of malignant hyperthermia reactions ranges from 1:5,000 to 1:250,000 anesthetics 5, 7.
  • The syndrome is inherited in an autosomal dominant pattern in humans 5, 7, 8.
  • Genetic mutations in the ryanodine receptor type 1 (RYR1) and CACNA1S genes have been identified in malignant hyperthermia-susceptible individuals 5, 6, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Malignant hyperthermia.

The Journal of craniofacial surgery, 2003

Research

Malignant hyperthermia.

Orphanet journal of rare diseases, 2007

Research

The current status of malignant hyperthermia.

Journal of biomedical research, 2019

Research

Malignant hyperthermia: a review.

Orphanet journal of rare diseases, 2015

Research

Malignant hyperthermia: a review.

Journal of perinatology : official journal of the California Perinatal Association, 1992

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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