Epidemiology

Etiology

• Inherited susceptibility: primarily autosomal dominant with reduced penetrance
  • ∼ 50% of cases: associated with a mutation in the ryanodine receptor type 1 (RYR-1)
    • RYR1 primarily in skeletal myocytes, RYR2 primarily in cardiac myocytes, and RYR3 in various cells including neurons.
• Triggering agents
  • Volatile anesthetics (except nitrous oxide)
  • Succinylcholine

Pathophysiology

• Administration of triggering substances → calcium release from intracellular compartments or delay in its reuptake → ↑ calcium in muscle cells → ↑ contractility of the skeletal muscle → ↑ metabolism → ↑ oxygen consumption in addition to ↑ CO₂ production, heat, and lactate (malignant hyperthermia) → mixed respiratory and metabolic acidosis → uncoupled oxidative phosphorylation → breakdown of the cell's energy supply → cell death

Clinical features

• Early signs
  • Tachycardia
  • Tachypnea
  • Cyanosis
  • Generalized rigidity, masseter rigidity
• Late signs
  • Elevated body temperature (up to 45ºC/113°F)
  • Signs of secondary organ damage
    • Myoglobinuria, muscle pain, swelling, and weakness of the affected muscles (rhabdomyolysis)

Diagnostics

• Respiratory parameters: continuous increase in end-tidal CO₂

Treatment

• Discontinuation of potential triggering agents
• Immediate administration of dantrolene (ryanodine receptor antagonist)
  • Mechanism of action
    • Ryanodine receptor antagonist
    • Prevents release of calcium from the sarcoplasmic reticulum of striated muscle → reduced muscle rigidity and hyperthermia