ISSN 2398-2969      

Malignant hyperthermia

icanis
Contributor(s):

Simon Platt

Simon Tappin

Synonym(s): Canine stress syndrome, malignant hyperthermia syndrome, malignant hyperthermia susceptibility and malignant hyperpyrexia


Introduction

  • Cause: malignant hyperthermia is caused by uncontrolled intracellular calcium release from the sarcoplasmic reticulum of skeletal muscle, leading to sustained muscular contraction. This can be triggered by excitement, stress or a number of drugs, including anesthetic agents. In dogs an autosomal dominant mutation in the ryanodine receptor has been described.
  • Signs: hyperthermia secondary to sustained muscular contraction, leading to muscular stiffness, hypercapnia, tachycardia, tachypnea and possible seizures.
  • Diagnosis: PCR of DNA obtained by buccal swab or blood sampling orin vitromuscular contraction tests.
  • Treatment: cooling and symptomatic therapy. Dantrolene to block sarcoplasmic calcium release.
  • Prognosis: guarded but proportional to the severity of the hyperthermia.

Pathogenesis

Etiology

  • Malignant hyperthermia is caused by uncontrolled intracellular calcium release from the sarcoplasmic reticulum of skeletal muscle. This can be triggered by excitement, stress or a number of drugs, including anesthetic agents (see below).
  • In man the disease is considered a clinical syndrome (Malignant hyperthermia syndrome - MHS) with multiple potential genetic and environmental triggers that lead to the same clinical signs.
  • Classically in malignant hyperthermia in both man and pigs, skeletal muscle contraction occurs early in the disease process and lead to increased carbon dioxide production and lactic acidosis. In dogs increased production of carbon dioxide typically develops prior to the onset of muscular rigidity and hyperthermia Hyperthermia.
  • A defect in the ryanodine receptor (RYR1 - V547A) has been described in North America in dogs susceptible to malignant hyperthermia as diagnosed by anin vitrocontracture test (Robertset al, 2001).

Predisposing factors

General
  • Stress.
  • Exercise.
  • Excitement.

Specific

  • Anesthetic agents including:
    • Inhalation agents such as halothane Halothane.
    • Depolarizing neuro-muscular agents such as succinylcholine.
  • Fermented hops (Duncanet al, 1997) Hops toxicity.
  • Caffeine.

Pathophysiology

  • Muscular contraction occurs in response to a depolarizing action potential, which arrives through the neuromuscular junction.
  • Depolarization of voltage-gated calcium channels, leads to a change in conformation, opening the ryanodine receptor (RYR1) and allows the release of calcium in to the cytosol, which leads to muscular contraction.
  • Mutations in the RYR1 gene lead to malignant hyperthermia as the result of abnormalities of calcium regulation within muscle.
  • In people abnormalities in other genes such as those that code for calcium adenosine triphosphatase and skeletal muscle sodium channels have also been associated with the malignant hyperthermia susceptibility.

Timecourse

  • Signs rapidly develop after the triggering insult.

Epidemiology

  • Malignant hyperthermia is a rare condition, but its exact incidence is unknown.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Brunson D B, Hogan K J (2004) Malignant hyperthermia: a syndrome not a disease. Vet Clin North Am Small Anim Pract 34 (6), 1419-1433 PubMed.
  • Roberts M C et al (2001) Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1). Anesthesiology 95 (3), 716-725 PubMed.
  • Duncan K L et al (1997) Malignant hyperthermia-like reaction secondary to ingestion of hops in five dogs. J Am Vet Med Assoc 210 (1), 51-54 PubMed.
  • Kirmayer H et al (1984) Malignant hyperthermia in a dog: case report and review of the syndrome. J Am Vet Med Assoc 185 (9), 978-982 PubMed.
  • O'Brien P J et al (1983) Canine malignant hyperthermia: diagnosis of susceptibility in a breeding colony. Can Vet J 24 (6), 172-177 PubMed.

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