Malignant Hyperthermia

• Nature of Condition: A rare, life-threatening pharmacogenetic disorder of skeletal muscle calcium regulation.

• Genetic Mechanism:

  • Mutations: Primarily in the ryanodine receptors (RYR1) and dihydropyridine receptors.

  • Cellular Action: Altered function of calcium release channels leads to a massive release of calcium into the myofibril cytoplasm.

  • Result: Generalized, extensive skeletal muscle contraction that leads to a fatal hypermetabolic state.

• Heredity:

  • Pigs: Autosomal recessive (both parents must carry the gene).

  • Dogs/Humans: Mutant autosomal gene is dominant.

Species Susceptibility

• High Susceptibility: Pigs (especially Pietrain, Poland China, and Landrace) and humans.

• Reported In: Dogs (Pointers, Greyhounds, Labs, etc.), cats, and horses.

• Rare/Not Reported: No reports of MH induced by modern halogenated anesthetics in cattle.

Triggering Agents

• Anesthetics:

  • Halogenated Inhalation Agents: Halothane (most potent), isoflurane, sevoflurane, and desflurane.

  • Depolarizing Neuromuscular Blockers: Succinylcholine.

• Environmental/Physical Factors:

  • Stress: Excitement, transportation, and preanesthetic handling.

  • Exercise: Intense physical activity can trigger an episode in susceptible animals.

Clinical Findings & Progression

• Early/Subtle Signs: Tachycardia, rapid rise in end-tidal CO2 (ETCO), and muscle rigidity.

• Full-Fledged Episode (Fulminant):

  • Sudden, dramatic rise in body temperature (often a late sign).

  • Muscle fasciculation and rigidity.

  • Arrhythmias, tachypnea, and metabolic acidosis.

  • Myoglobinuria leading to renal failure and often death.

• Species-Specific Nuances:

  • Dogs: The first indicator is usually a dramatic increase in CO2

  • production, which occurs before the temperature rise.

  • Pigs: May develop red/blotched skin and rapid rigor mortis.

  • Horses: Often slow to develop (appearing after 3 hours of anesthesia) and easily confused with other myopathies.

Diagnosis

• In Vitro Contracture Test (IVCT): The "gold standard"; involves testing muscle fiber response to halothane or caffeine via biopsy.

• DNA Analysis: Screens for known RYR1 mutations; less invasive as it only requires a blood sample.

• Supportive Care:

  • Acidosis: Sodium bicarbonate to maintain blood pH.

  • Hyperkalemia: 50% dextrose or insulin to shift potassium back into cells.

  • Arrhythmias: Lidocaine.

• Contraindications: Calcium chloride and calcium gluconate are strictly contraindicated.

• Prevention:

  • Avoid known triggers in susceptible lines.

  • Use alternative anesthetics (e.g., propofol, ketamine, opioids, or benzodiazepines).

  • Minimize pre-surgical stress through effective sedation.