Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible.

The most common triggering agents are volatile anesthetic gases, such as halothane, sevoflurane, desflurane, isoflurane, enflurane or the depolarizing muscle relaxants suxamethonium and decamethonium used primarily in general anesthesia.

[5][7] In fact, malignant hyperthermia susceptibility (MHS), predisposed by mutations in the skeletal muscle calcium release channel (RYR1), is one of the most severe heat-related illnesses.

Some examples of drugs that don't cause MH include local anesthetics (lidocaine, bupivacaine, mepivacaine), opiates (morphine, fentanyl), ketamine, barbiturates, nitrous oxide, propofol, etomidate, and benzodiazepines.

The nondepolarizing muscle relaxants pancuronium, cisatracurium, atracurium, mivacurium, vecuronium and rocuronium also are generally thought to be safe for patients MH.

[9] There is mounting evidence that some individuals with malignant hyperthermia susceptibility may develop MH with exercise and/or on exposure to hot environments.

[citation needed] In a large proportion (50–70%) of cases, the propensity for malignant hyperthermia is due to a mutation of the ryanodine receptor (type 1), located on the sarcoplasmic reticulum (SR), the organelle within skeletal muscle cells that stores calcium.

[19] Research into malignant hyperthermia was limited until the discovery of "porcine stress syndrome" (PSS) in Danish Landrace and other pig breeds selected for muscling, a condition in which stressed pigs develop "pale, soft, exudative" flesh (a manifestation of the effects of malignant hyperthermia) rendering their meat less marketable at slaughter.

These mice display signs similar to human MH patients, including sensitivity to halothane (increased respiration, body temperature, and death).

[citation needed] Malignant hyperthermia is diagnosed on clinical grounds, but various laboratory investigations may prove confirmatory.

These include a raised creatine kinase level, elevated potassium, increased phosphate (leading to decreased calcium) and—if determined—raised myoglobin; this is the result of damage to muscle cells.

Patients may also experience premature ventricular contractions due to the increased levels of potassium released from the muscles during episodes.

[citation needed] The main candidates for testing are those with a close relative who has had an episode of MH or have been shown to be susceptible.

The fresh biopsy is bathed in solutions containing caffeine or halothane and observed for contraction; under good conditions, the sensitivity is 97% and the specificity 78%.

Intramuscular injection of halothane 6 vol% has been shown to result in higher than normal increases in local pCO2 among patients with known malignant hyperthermia susceptibility.

In this test, intramuscular injection of caffeine was followed by local measurement of the pCO2; those with known MH susceptibility had a significantly higher pCO2 (63 versus 44 mmHg).

The higher the score (above 6), the more likely a reaction constituted MH:[29] In the past, the prophylactic use of dantrolene was recommended for MH-susceptible patients undergoing general anesthesia.

[30] However, multiple retrospective studies have demonstrated the safety of trigger-free general anesthesia in these patients in the absence of prophylactic dantrolene administration.

The largest of these studies looked at the charts of 2214 patients who underwent general or regional anesthesia for an elective muscle biopsy.

Only five of these patients exhibited signs consistent with MH, four of which were treated successfully with parenteral dantrolene, and the remaining one recovered with only symptomatic therapy.

[31] After weighing its questionable benefits against its possible adverse effects (including nausea, vomiting, muscle weakness and prolonged duration of action of nondepolarizing neuromuscular blocking agents[32]), experts no longer recommend the use of prophylactic dantrolene prior to trigger-free general anesthesia in MH-susceptible patients.

[33] Charcoal filters can be used to prepare an anesthesia machine in less than 60 seconds for people at risk of malignant hyperthermia.

These filters prevent residual anesthetic from triggering malignant hyperthermia for up to 12 hours, even at low fresh gas flows.

[34] Prior to placing the charcoal filters, the machine should be flushed with fresh gas flows greater than 10 L/min for 90 seconds.

[35] The current treatment of choice is the intravenous administration of dantrolene, the only known antidote, discontinuation of triggering agents, and supportive therapy directed at correcting hyperthermia, acidosis, and organ dysfunction.

[37] Conducting MH crisis training for perioperative teams can identify system failures as well as improve response to these events.

[38] Simulation techniques to include the use of cognitive aids have also been shown to improve communication in clinical treatment of MH.

[45] The efficacy of dantrolene as a treatment was discovered by South African anesthesiologist Gaisford Harrison and reported in a 1975 article published in the British Journal of Anaesthesia.

The hotline became active in 1982 and since that time MHAUS has provided continuous access to board-certified anesthesiologists to assist teams in treatment.

[51] Azumolene is a 30-fold more water-soluble analog of dantrolene that also works to decrease the release of intracellular calcium by its action on the ryanodine receptor.