DESCRIPTION

• Malignant hyperthermia (MH) is a pharmacogenetic disease of skeletal muscle.
• MH presents as an acute hypermetabolic crisis, with sustained muscle contraction after exposure to a trigger.
• Known pharmacologic triggers are the volatile anesthetics sevoflurane, isoflurane, desflurane, halothane, ether, and the depolarizing muscle relaxant, succinylcholine.
• Rarely, a physiologic stressor such as exercise can trigger MH.
• Hypermetabolic syndrome can present with hypercarbia, hyperthermia, tachycardia, generalized muscle rigidity, arrhythmias, myoglobinuria, and mixed metabolic and respiratory acidosis.
• Following treatment, MH can reoccur within 24 hours of the prior episode.
• The clinical presentation of MH is variable. MH is potentially fatal.

EPIDEMIOLOGY

• MH has a male preponderance.
• MH occurs more commonly in children and young adults, with children <19 years of age constituting up to 52% of reported MH events.
• Not all exposure events in each MH-susceptible patient will result in a triggering event or MH crisis.
• Once a patient has one triggering event, they will always trigger during subsequent anesthetics.
• Mortality estimates are between 4% and 12%.
• Studies estimate a prevalence of 1:100,000 operations; however, this likely represent an underestimate.
• The prevalence of genetic susceptibility to MH may be as high as 1:2,000 to 3,000.
• Due to the variable penetrance, not all exposures of MH-susceptible patients to triggering agents will result in an MH crisis.

RISK FACTORS

• History of cola-colored urine after anesthesia
• Masseter muscle spasm or trismus
• Succinylcholine-induced trismus increases likelihood of MH susceptibility to as much as 50%.

GENERAL PREVENTION

• Obtain a family history regarding exposure to anesthetics and any types of reactions/complications.
• If any 1st- or 2nd-degree relatives have a history of MH reaction, or concern exists that the patient is at risk for MH, you must assume the patient is MH susceptible and avoid administering triggering agents.
• A caffeine-halothane contracture test can be obtained to establish the diagnosis but requires muscle biopsy (see “Ongoing Care” section).

PATHOPHYSIOLOGY

• Normal skeletal muscle contraction is regulated by calcium. Depolarization of the T-tubule causes the ryanodine receptor on the sarcoplasmic reticulum membrane to open and release calcium. Calcium initiates contraction by binding to troponin which then allows for actin and myosin to interact. Muscle relaxation occurs when calcium is pumped back into the sarcoplasmic reticulum.
• In MH, a trigger exposure causes the uncontrolled release of calcium through the RyR1 receptor located on the sarcoplasmic reticulum. This results in calcium accumulation which causes a sustained muscle contraction and a depletion of adenosine triphosphate (ATP) stores.
• Continuous muscle contraction results in excessive increases in oxygen consumption, carbon dioxide (CO₂) production, heat production, and failure of the cell to maintain its membrane structure. This results in leakage of myoglobin, potassium, and creatinine kinase into the blood circulation.

COMMONLY ASSOCIATED CONDITIONS

MH has definitive relationship to:

• Central core disease
• Multiminicore disease
• King-Denborough syndrome