Makindo Medical Notes

Related Subjects: Acute Kidney Injury |Acute Rhabdomyolysis |Hyperkalaemia

Thanks to significant advances in understanding the clinical manifestation and pathophysiology of Malignant Hyperthermia (MH), mortality rates have dropped from over 80% thirty years ago to less than 5% today.

About

• Usually precipitated by drugs in genetically susceptible individuals, though previous uneventful anesthesia with triggering agents does not preclude the development of MH.
• Characterized by hypermetabolism, acidosis, rhabdomyolysis, and hyperkalaemia, MH is invariably fatal if untreated.

Aetiology

• Typically an autosomal dominant inherited predisposition, occurring in 1 in 20,000 individuals.
• At least four chromosomal locations have been identified; the most well-known is the Ryanodine receptor mutation on chromosome 19q13.
• The acute rise in intracellular calcium causes muscle rigidity and rhabdomyolysis.

Pathogenesis

Malignant Hyperthermia involves uncontrolled release of calcium from the sarcoplasmic reticulum of skeletal muscle, leading to hypermetabolic states.

Causes

• Inhalational anesthetics: Halothane, Sevoflurane, Desflurane
• Depolarizing muscle relaxants such as Succinylcholine
• Other triggers: Vigorous exercise and heat

Clinical Features

• One of the earliest and most specific signs is an increase in end-tidal CO₂ (ETCO₂).
• Trunk or generalized body rigidity is common.
• Masseter muscle spasm or trismus may be an early warning sign.
• Hyperpyrexia (>40°C), myoglobinuria (dark urine), tachycardia, and muscle stiffness.

Differential Diagnosis

• Light anesthesia
• Hypoventilation
• Thyroid storm
• Overheating
• Phaeochromocytoma

Investigations

• Blood tests: U&E to assess renal function, especially in cases of myoglobinuria. Elevated potassium (K+), elevated Creatine Kinase (CK).
• ABG: Metabolic and respiratory acidosis with elevated CO₂ production.
• ECG: Continuous monitoring for arrhythmias and signs of hyperkalaemia.

Complications

• Acute kidney injury (AKI)
• Cardiac arrhythmias and cardiac arrest
• Hyperkalaemia
• Disseminated Intravascular Coagulation (DIC)

Management: Avoid Calcium Channel Blockers

• ABC Management: If untreated, MH is potentially fatal due to uncontrolled hypermetabolism leading to cellular hypoxia and metabolic acidosis. Notify the surgical team immediately.
• Stop the triggering agent: Halt surgery if possible and switch to intravenous anesthetics (e.g., Propofol). If hyperthermia is present, consider cavity ice water lavage.
• ICU Admission: Insert central line and urinary catheter, and monitor for hyperkalaemia with Insulin/Dextrose and Calcium Gluconate if ECG changes are present.
• Hyperventilation: Use 100% oxygen (>10 L/min) via a clean breathing circuit. If an anesthetic machine is unavailable, use an Ambu bag and O₂ cylinder.
• Active Cooling: Use cool IV fluids and ice packs to lower body temperature. Antipyretics are ineffective.
• Dantrolene: Administer 2-3 mg/kg IV initially, then 1 mg/kg as needed, up to a maximum of 10 mg/kg. Caution as extravasation can cause soft tissue injury.
• IV Bicarbonate: Consider for metabolic acidosis (pH < 7.2) or hyperkalaemia.

References

• Malignant Hyperthermia - FRCA
• Malignant Hyperthermia - NCBI