What can induce malignant hyperthermia?

Malignant Hyperthermia: Triggers and Characteristics

Malignant hyperthermia is triggered by potent inhalational anesthetics and succinylcholine (depolarizing muscle relaxant), but NOT by local anesthetics, non-depolarizing muscle relaxants, or nitrous oxide, and it occurs more frequently in children than adults. 1

Triggering Agents

Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disease with specific triggering agents:

• Confirmed triggers:

  • Potent inhalational anesthetics (sevoflurane, desflurane, isoflurane, etc.) 1, 2
  • Succinylcholine (depolarizing muscle relaxant) 1, 2

• Non-triggering agents:

  • Local anesthetics 3, 4
  • Non-depolarizing muscle relaxants 3, 4
  • Nitrous oxide 3, 4
  • Intravenous induction agents (propofol, etc.)
  • Benzodiazepines
  • Opioids

Epidemiology and Demographics

• Incidence of MH ranges from 1:10,000 to 1:250,000 general anesthetics 1
• Higher reported incidence in pediatric populations compared to adults 1
• Consistently higher incidence in males compared to females 1
• Mortality has decreased from 70-80% historically to approximately 4% in the UK with modern treatment 1

Pathophysiology

MH involves dysregulation of intracellular calcium in skeletal muscle:

• Triggering agents cause excessive calcium release from sarcoplasmic reticulum 5
• This leads to sustained muscle contraction and hypermetabolism 1
• Results in increased oxygen consumption and carbon dioxide production
• Progressive increase in body temperature occurs as heat dissipates from skeletal muscle 1

Clinical Presentation

Early recognition is critical for survival. Key clinical features include:

1. Early signs:

   • Increasing heart rate (most consistent early sign) 1
   • Rapidly rising end-tidal CO2 despite increased ventilation
   • Masseter muscle spasm (especially after succinylcholine) 1, 6
   • Generalized muscle rigidity

2. Later signs:

   • Rapidly increasing body temperature (>0.5°C in 15 minutes) 7
   • Mixed metabolic and respiratory acidosis
   • Hyperkalaemia and arrhythmias
   • Mottled skin (more common in children) 1
   • Rhabdomyolysis with myoglobinuria

Treatment

Immediate treatment is essential:

• Discontinue triggering agents immediately
• Hyperventilate with 100% oxygen
• Administer dantrolene (2.5 mg/kg initially, repeated as needed) 5
• Cooling measures
• Treat metabolic derangements
• Monitor for at least 24 hours as recurrence can occur 3

Important Considerations

• MH susceptibility is inherited as an autosomal dominant trait with variable penetrance 3
• Previous uneventful anesthesia does not rule out MH susceptibility 1
• The timing of MH reactions is highly variable - can occur within minutes or be delayed for hours 1
• Patients with Duchenne muscular dystrophy and certain other myopathies may be at increased risk 3

Diagnostic Testing

• In vitro contracture test (IVCT) is the standard test for MH susceptibility 1
• Genetic testing can identify some but not all susceptible individuals due to genetic heterogeneity 1

The correct answer regarding malignant hyperthermia is D. It is more common in children than adults, as clearly indicated by the epidemiological data in the guidelines 1.