Malignant hyperthermia (MH) is a rare, autosomal dominant condition involving mutations in the ryanodine receptor type 1 (RYR-1) causing an aberrant calcium-induced calcium release (CICR) mechanism. With normal skeletal muscle contraction, an impulse is sent down the T-tubules releasing calcium from the sarcoplasmic reticulum via the RYR-1 ion channel; however in MH, an unusually high CICR due to a faulty RYR-1 channel leads to very large concentrations of intracellular calcium overwhelming the normal reuptake machinery. This leads to sustained contraction, increased temperature from the ATP-intense process of reuptake, potential organ damage, and even death.
The caffeine-halothane contracture test (CHCT) is a very sensitive, gold standard test for diagnosing MH whereas genetic testing only has ~30% sensitivity although it’s very specific. That being said, MH should always be in our mind with every anesthetic where triggering agents like succinylcholine or halogenated volatile agents (sevoflurane, isoflurane, desflurane) are utilized.
Symptoms of MH include hyperthermia, masseter muscle contracture, respiratory acidosis (increased end-tidal CO2), tachycardia, profound muscle rigidity, and cardiac arrhythmias. Labs might show hyperkalemia, elevated creatinine kinase, acidosis and myoglobinuria – all related to increased skeletal muscle metabolism and breakdown.
Treatment for MH is centered around dantrolene, a drug which binds RYR and decreases calcium release. Reconstituting the drug in sterile water can be a laborious task to achieve the initial dose of 2.5 mg/kg, so call for help! Fortunately, formulations like RYANODEX can facilitate this task! Additionally, triggering agents should be discontinued, the patient should be cooled, and electrolytes/acid-base should be corrected aggressively.
Patients with a history of MH can still SAFELY receive anesthesia for surgery with techniques like total intravenous anesthesia (TIVA), regional/neuraxial anesthesia, or even monitored anesthesia care (MAC) depending on the procedure. Nevertheless, these patients should still be monitored very carefully for signs of MH.