Malignant hyperthermia (MH or MHS for "malignant hyperthermia syndrome", or "malignant hyperpyrexia due to anesthesia") is a life-threatening condition resulting from a genetic sensitivity of skeletal muscles to volatile anesthetics and depolarizing neuromuscular blocking drugs that occurs during or after anaesthesia. It is related to, but distinct from, the neuroleptic malignant syndrome.
Signs, Symptoms and Diagnosis
The phenomenon presents with muscular rigidity, followed by a hypermetabolic state showing increased oxygen consumption, increased carbon dioxide production and hypercarbia, and increased temperature (hyperthermia), proceeding to rhabdomyolysis with rapid rising of blood levels of myoglobin, creatine kinase (CK/CPK) and potassium.
Halothane, a once popular but now rarely used volatile anesthetic, has been linked to a large proportion of cases, however, all volatile anesthetics are potential triggers of malignant hyperthermia. Succinylcholine, a neuromuscular blocking agent, may also trigger MH. MH does not occur with every exposure to triggering agents, and susceptible patients may undergo multiple uneventful episodes of anesthesia before developing an episode of MH. The symptoms usually develop within one hour after anesthesia.
Testing for susceptibility to MH is by muscle biopsy done at an approved center under local anesthesia. The fresh biopsy is bathed in a solution containing caffeine and halothane (the "caffeine-halothane contracture test", CHCT) and observed for contraction; under good conditions, the sensitivity is 97% and the specificity 78% (Allen et al., 1998). Negative biopsies are not definitive, so any patient who is suspected to have MH by history is generally treated with non-triggering anesthetics even if the biopsy was negative. Some researchers advocate the use of the "calcium-induced calcium release" test in addition to the CHCT to make the test more specific.
The current treatment of choice is the intravenous administration of dantrolene. Treatment must be instituted rapidly on clinical suspicion of the onset of malignant hyperthermia.
Dantrolene is a muscle relaxant that works directly on the ryanodine receptor to prevent the release of calcium. Pretreatment with dantrolene has been advocated in the past to prevent MH, but this is probably unreliable, and the long half-life of the drug may leave patients weak for extended periods. The only sure way to prevent MH is avoid the use of triggering agents in patients known or suspected of being susceptible to MH.
After the widespread introduction of treatment with dantrolene the mortality of malignant hyperthermia fell from 80% in the 1960s to less than 10%.
The substance azumolene, chemically related to dantrolene, is under investigation for use in MH.