Pathophysiology
Clinical meaning
Malignant hyperthermia is triggered when susceptible individuals with RYR1 mutations are exposed to volatile anesthetics or depolarizing neuromuscular blocking agents. The mutation causes the ryanodine receptor in the sarcoplasmic reticulum to become hypersensitive, releasing massive amounts of calcium into the myoplasm. This sustained calcium release causes continuous muscle contraction and hypermetabolism, consuming ATP and oxygen at exponential rates while producing excessive CO2, heat, and lactic acid. As ATP stores are depleted, sarcolemma integrity fails, releasing intracellular contents including potassium, myoglobin, and creatine kinase into the bloodstream. This leads to life-threatening hyperkalemia, metabolic acidosis, rhabdomyolysis with acute kidney injury, disseminated intravascular coagulation, and cardiac arrest. The nurse must coordinate the emergency response, administer dantrolene, implement aggressive cooling, and manage metabolic derangements simultaneously.