Malignant hyperthermia (MH) is an inherited myopathy characterized by a hypermetabolic state which is triggered when the patient is exposed to some anesthetic agents. Classic MH most often manifests in the operating room, but it can also occur within the first few hours of recovery from anesthesia.
The syndrome is though to be due to a reduction in the reuptake of calcium by the sarcoplasmic reticulum necessary for termination of muscle contraction. Consequently, muscle contraction is sustained, resulting in signs of hypermetabolism, including acidosis, tachycardia, hypercarbia, glycolisis, hypoxemia, and heat production (hyperthermia).
Some susceptible patients may develop MH despite multiple prior uneventful exposures to triggering drugs. Tipically MH is triggered by succinylcholine(Sch) or volatile anesthetics. Some other drugs have been found safe in patients susceptible to MH. See Table 1
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MH is estimated to occur in 1 in every 15000 pediatric anesthetics and 1 in every 50000 adults anesthetics, with a mortality rate of about 10%.
Inheritance of MH is autossomal dominant with variable penetrance, such that 50% of children of MH susceptible parents are potentially at risk.
A mutation in the ryanodine receptor(a calcium release channel) has been shown to cause MH in about 20% of affected human families.
Other two mutations have been isolated and mapped - fc20 and fc34 - and seem to cause MH-like responses to volatile anesthetics, without involving the ryanodine receptor.
The initial signs of MH are increase in end-tidal carbon dioxide and decrease in arterial oxygen saturation, tachycardia and dysrhythmias, rigidity (despite the use of muscle relaxant), and tachypnea (in spontaneously breathing patients). An unexplained tachycardia, however, is usually the fist sign. Other findings are hyperthermia and cyanosis. See Table 2. When clinical signs are suggestive of MH, several laboratory tests may lead to a presumptive diagnosis. A blood gas analysis may be obtained to determine whether metabolic acidosis is present (venous blood is better than arterial to observe the immense production of carbon dioxide). Other possible metabolic abnormalities include hyperkalemia, hypercalcemia, hyperphosphatemia, creatine kinase levels >1000 IU, and myoglobinuria. All these tests are suggestive of the diagnosis of MH, but not definitive.
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A suspicion that testing is needed is based on patient’s history, positive family history, or use of an anesthetic remarkable for clinical diagnosis of MH. Key features in the patient’s history include strabismus, myalgias on exercise, tendency to fever, myoglobinuria, muscular disease, and intolerance of caffeine.Patients requiring a more definitive diagnosis are referred for muscle biopsy.
Although several tests have been described, the halothane-caffeine contracture test remains the gold standard. It is performed on muscle obtained by biopsy (usually the vastus lateralis), which is bathed on a solution containing 1-3% halothane and caffeine - they decrease the threshold for muscle contraction and therefore facilitate diagnosis. This test is 85% specific and 100% sensitive. Creatine phosphokinase is elevated 70% of susceptible patients. A genetic test of the ryanodine receptor may eventually be developed.
When MH is diagnosed early and treated promptly, the mortality rate should be near zero. Whenever anesthesia is administrated, dantrolene should be readily available as well as a protocol for management of MH. Dantrolene is, at the moment, the only known drug that treats MH. It impairs calcium-dependent muscle contraction and controls hypermetabolism manifestations. See on Table 3treatment of MH step by step.
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There have been no deaths from MH in previously diagnosed MH susceptible patients when the anesthesiologist was prospectively aware of the problem. This information is useful to allay patient’s preoperative anxiety. In a MH-susceptible parturient, it should be considered first an epidural anesthesia without dantrolene pretreatment, and close monitoring of vital signs. If general anesthesia is necessary for delivery, follow the same steps of management of MH-susceptible patients on Table 4. No adverse fetal effects of dantrolene have been observed .
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After an intubating dose of Sch with loss of twitches on neuromuscular stimulation, difficulty in opening the mouth represents Masseter Muscle Rigidity (MMR). Such patients may be susceptible to MH.The incidence of MMR is 1% in children induced with halothane and Sch, and 2.8% in children having strabismus surgery. Such patients are prone to an increase in creatinin kinase, myoglobinuria, tachycardia, and dysrhythmias independent of MH. It is controversial whether to proceed with an anesthetic if the patient develops MMR. Some anesthesiologists elect to cancel the schedule procedure, whereas others continue the case using non - triggering agents of MH.
There is a strong correlation between Central Core Disease (a sarcoplasmic myopathy characterized by proximal muscle weakness) and MH. Case reports have also linked MH to Muscular Dystrophy and forms of Myotonia.
Rosemberg H, Seitman D, Fletcher J: Pharmacogenetics. In Barash PG , Cullen BF, Stoelting RK [eds]: Clinical Anesthesia, pp 589-613. Philadelphia, JB Lippincott, 1992.
Raines D, Chang BSP, Patafio O: Intraanesthetic problems. In Davison JK, Eckardt IIIWF, Perese DA [eds]: Clinical Anesthesia Procedures of the Massachusetts General Hospital, pp 247-272. Little Brown, 1993.
Weiss L: Malignant Hyperthermia. In Duke J, Rosemberg SG [eds]: Anesthesia Secrets, pp 320-322. Hanley & Belfus, 1996.
Morgan P, Sendensky M: Malignant Hyperthermia in C. Elegans (Hot Worms). In Early 1995 International Worm Meeting abstract 250. URL: http://www.sanger.ac.uk/abstracts95/breakout/wm95e250.htm
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