Malignant hyperthermia (MH) is a life-threatening pharmacogenomic disorder triggered by certain anesthetic agents (e.g., halothane) or depolarizing muscle relaxants like succinylcholine. These agents cause uncontrolled calcium release in skeletal muscles, leading to hyperthermia, rigidity, metabolic acidosis, rhabdomyolysis, and cardiac arrhythmias.

Key Features:

1. Onset:

   • Occurs most commonly during anesthesia in the operating room but may also manifest in the early postoperative period.
   • Initial signs include masseter spasm, tachycardia, and tachypnea.

2. Trigger Agents:

   • Volatile anesthetics and depolarizing muscle relaxants.
   • Prior tolerance does not guarantee future safety.

3. Inheritance and Risk Factors:

   • Autosomal dominant inheritance.
   • Commonly associated with RYR1 and CACNA1S mutations.

4. Associated Disorders:

   • Central core disease, King-Denborough syndrome, and multiminicore myopathy.
   • Rare associations include nemaline myopathy, Schwartz–Jampel syndrome, and STAC3 myopathy.

Diagnosis:

1. In Vitro Contracture Test (IVCT):

   • Evaluates muscle response to graded concentrations of caffeine and halothane.
   • Sensitivity approaches 100%; specificity ranges from 80% to 97% (Allen et al., 1998).
   • Requires a fresh muscle biopsy but is not well standardized for children.

2. Genetic Testing:

   • Tests for RYR1 and CACNA1S mutations are clinically available.

3. Differential Diagnosis:

   • Includes sepsis, hyperthermia, pheochromocytoma crisis, thyrotoxicosis, and anesthesia-induced rhabdomyolysis in dystrophinopathies.
   • Muscle rigidity in myotonic syndromes may mimic MH but has a distinct mechanism.

Treatment:

1. Immediate Interventions:

   • Terminate triggering anesthetic agents.
   • Initiate active body cooling.
   • Correct metabolic acidosis.

2. Pharmacological Management:

   • Dantrolene Sodium: Initial dose of 1–2 mg/kg IV, repeated every 5–10 minutes as needed, up to a maximum dose of 10 mg/kg (Racca et al., 2013).
   • Dantrolene inhibits calcium release from the sarcoplasmic reticulum, reversing the hypermetabolic state.

3. Supportive Care:

   • Hydration to prevent kidney damage from myoglobinuria.
   • Monitor for complications like arrhythmias and disseminated intravascular coagulation (DIC).

Precautions:

1. Avoid known trigger agents in susceptible patients.
2. Family members should undergo screening for elevated creatine kinase levels or genetic susceptibility.
3. Non-triggering anesthetics (e.g., total intravenous anesthesia) should be used for at-risk individuals.

Prognosis:

With prompt diagnosis and treatment, the outcomes of MH have improved significantly. However, it remains a critical cause of anesthesia-related morbidity and mortality.