1. Malignant hyperthermia (MH) is a pharmacogenetic disease characterized by extreme hypermetabolism when a genetically susceptible individual is exposed to a triggering agent.
   1. The clinical features are a result of hypermetabolism and include an increase in end-tidal CO₂, tachycardia, tachypnea, metabolic acidosis, muscle rigidity, and possibly rhabdomyolysis. All potent, inhaled halogenated anesthetics and SCh are triggering agents.
   2. The final common pathway that leads to MH is uncontrolled release and regulation of calcium in muscle sarcoplasm. The calcium release channel in human muscle is the ryanodine receptor (RYR), and mutations in the receptor may cause MH in susceptible patients.
   3. The discovery that dantrolene was effective for the treatment of MH has dramatically reduced the mortality rate from MH.
   4. Management of the Acute Malignant Hyperthermia Episode (Table 23-9: Treatment of an Acute Episode of Malignant Hyperthermia)
   5. A clinical grading system can be used to objectively evaluate a suspected MH episode and aid in referral of patients for definitive testing (Table 23-10: Criteria Used in the Malignant Hyperthermia).
   6. Management of the Malignant Hyperthermia–Susceptible Patient
      1. Anesthesia for malignant hyperthermia susceptible (MHS) patients is based on avoidance of triggering agents such as halogenated, inhaled anesthetics, and SCh (Table 23-11: Safe Versus Unsafe Drugs in Malignant Hyperthermia). Regional anesthesia is suitable for MHS patients.
      2. The Malignant Hyperthermia Association of the United States has recommendations for purging anesthesia machines to reduce trace concentrations of volatile anesthetics to acceptable levels. (Insertion of activated charcoal filters into the inspiratory and expiratory limbs of the anesthesia circuit rapidly reduces the concentration of trace volatile anesthetics.)
      3. Dantrolene does not have to be administered preoperatively but must be readily available.
2. Porphyria is caused by defects in the synthetic pathway of heme that lead to the accumulation of toxic intermediates. The main goal of anesthesia is to avoid triggering drugs in susceptible patients (Table 23-12: Drugs Known to Precipitate Porphyria). Drugs that have been administered without apparent complications include propofol, sevoflurane, desflurane, morphine, fentanyl, and ketamine. Regional anesthesia is also suitable.
3. Cholinesterase disorders are characterized by prolonged apnea after SCh. A prudent clinical practice is to be certain that recovery from the initial dose of SCh has occurred before administering additional muscle relaxant. If prolonged apnea after SCh occurs, laboratory testing is indicated (cholinesterase activity, dibucaine number).
4. Glycogen storage diseases (GSDs) are inherited disorders caused by abnormalities of enzymes that regulate glycogen synthesis and breakdown. The three common features of all forms of GSDs are acidosis, hypoglycemia, and cardiac and hepatic dysfunction.
5. Osteogenesis imperfecta is a genetic disease that results from defective synthesis of type I collagen. Preoperative evaluation should focus on the airway and cervical range of motion.

Rare Coexisting Diseases

1. Musculoskeletal Diseases
2. The Myotonias
3. Familial Periodic Paralysis
4. Myasthenia Gravis
5. Guillain-Barré Syndrome (Polyaradiculoneuritis)
6. Central Nervous System Diseases
7. Inherited Disorders
8. Anemias
9. Collagen Vascular Diseases
10. Skin Disorders