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Information

  1. Etiology. Malignant hyperthermia is a hypermetabolic syndrome occurring in genetically susceptible patients after exposure to an anesthetic triggering agent. Triggering anesthetics include all potent inhalational agents (eg, halothane, isoflurane, desflurane, and sevoflurane) and succinylcholine. The majority of cases are due to an inherited mutation in the ryanodine receptor, the calcium release channel in the sarcoplasmic reticulum. Abnormal function of this receptor causes reduction in the reuptake of Ca2+ by the sarcoplasmic reticulum necessary for the termination of muscle contraction. Consequently, muscle contraction is sustained, resulting in signs of hypermetabolism, including tachycardia, acidosis, hypercarbia, muscle rigidity, tachypnea, hypoxemia, and hyperthermia. Malignant hyperthermia usually occurs in the operating room, but onset may be delayed until the patient reaches the postanesthesia care unit or even the postoperative floor.
  2. Clinical features
    1. Unexplained tachycardia.
    2. Hypercarbia in the mechanically ventilated patient or tachypnea in the spontaneously breathing patient who is unresponsive to increased minute ventilation.
    3. Metabolic acidosis.
    4. Muscle rigidity even in the presence of neuromuscular blockade. Masseter spasm after giving succinylcholine is associated with malignant hyperthermia. However, not all patients who develop masseter spasm will develop malignant hyperthermia.
    5. Hypoxemia.
    6. Ventricular dysrhythmias.
    7. Hyperkalemia.
    8. Fever is often a late sign.
    9. Myoglobinuria.
  3. Treatment
    1. Summon help as soon as malignant hyperthermia is suspected. Discontinue all triggering anesthetics, and hyperventilate with 100% oxygen from a new source such as wall oxygen via an Ambu bag. Convert to a total intravenous anesthetic such as propofol. Surgery should be concluded as quickly as possible, and the anesthesia machine should be changed when feasible.
    2. Administer dantrolene or Ryanodex. Dantrolene (Dantrium), 2.5 mg/kg IV is given initially and repeated to a total of 10 mg/kg or more if signs of malignant hyperthermia persist. Dantrolene is the only known specific treatment for malignant hyperthermia. Its efficacy is due to its ability to inhibit Ca2+ release from the sarcoplasmic reticulum. Each ampule contains 20 mg of dantrolene and 3 g of mannitol and should be reconstituted with 50 mL of warm sterile water. Ryanodex is a newer formulation of dantrolene sodium with increased solubility. Each vial of Ryanodex contains 250 mg dantrolene sodium and 125 mg mannitol and should be reconstituted with 5 mL sterile water. Ryanodex dosing is the same as for the less-soluble dantrolene.
    3. Sodium bicarbonate administration should be guided by pH and partial pressure of carbon dioxide (PCO2) measurements.
    4. Hyperkalemia may be corrected with insulin, glucose, and an inhaled β-agonist (eg, albuterol). However, hypokalemia may occur as the hypermetabolic state is brought under control. Calcium administration should be avoided.
    5. Dysrhythmias generally subside with resolution of the hypermetabolic phase of malignant hyperthermia. Persistent dysrhythmias should be treated.
    6. Hyperthermia is treated by a variety of methods (see Section VIII).
    7. Urine output ideally should be maintained at 2 mL/kg/min to avoid renal tubular damage from myoglobin. A Foley catheter should be placed as soon as possible.
    8. Recrudescence, disseminated intravascular coagulation, and acute tubular necrosis may occur after an acute episode of malignant hyperthermia. Therefore, dantrolene therapy (1 mg/kg IV or orally every 6 hours) and close observation should be continued for 48 to 72 hours after an episode of malignant hyperthermia.
    9. Contact the malignant hyperthermia hotline if necessary at 1-800-MH-HYPER (1-800-644-9737) from within the United States. Information can also be obtained at www.mhaus.org.
  4. Anesthesia for malignant hyperthermia–susceptible patients
    1. A family history of anesthetic problems suggesting susceptibility, such as unexplained fevers or death during anesthesia, should be sought in every patient.
    2. Malignant hyperthermia (MH) may be triggered in susceptible patients who have had previous uneventful exposures to triggering agents.
    3. Pretreatment with dantrolene is not recommended for malignant hyperthermia–susceptible patients. A malignant hyperthermia cart or other dantrolene supply, however, should be immediately available.
    4. The anesthesia machine should be prepared by changing the carbon dioxide absorbent and fresh gas tubing, disconnecting the vaporizers, using a disposable breathing circuit with charcoal filters if available, and flushing the machine with oxygen at a rate of 10 L/min for at least 20 minutes. The preparation of modern anesthesia machines is variable. Some are more difficult to prepare and may require prolonged flushing times with maximal fresh gas flows, whereas others only require carbon filters in inspiratory and expiratory limbs of the circuit.
    5. Local or regional anesthesia should be considered, but general anesthesia with nontriggering agents is acceptable. Safe drugs for induction and maintenance of general anesthesia include barbiturates, propofol, benzodiazepines, opioids, and nitrous oxide. Nondepolarizing neuromuscular blockers may be used and safely reversed.
    6. Close monitoring for early signs of malignant hyperthermia such as unexplained hypercarbia or tachycardia is crucial.
  5. Associated syndromes. An increased risk of malignant hyperthermia has been reported in association with a number of disorders. In many of these cases, the association is not well established. However, patients with the following disorders should be treated as though they are susceptible to malignant hyperthermia:
    1. King-Denborough syndrome, characterized by dwarfism, mental retardation, and musculoskeletal abnormalities.
    2. Central core disease, a rare myopathy.
    3. Multiminicore disease, another rare myopathy.
    4. Duchenne muscular dystrophy and other muscular dystrophies are not associated with malignant hyperthermia but may be associated with hyperkalemia.
  6. Neuroleptic malignant syndrome (NMS) is associated with the administration of neuroleptic drugs and shares many of the features of malignant hyperthermia.
    1. Clinical features. NMS typically develops over 24 to 72 hours and is clinically similar to malignant hyperthermia, presenting as a hypermetabolic episode consisting of hyperthermia, autonomic nervous system instability, pronounced muscle rigidity, and rhabdomyolysis. Creatine kinase and hepatic transaminases often are increased, and mortality approaches 30%.
    2. Treatment of NMS is with dantrolene, although benzodiazepines, dopamine antagonists such as bromocriptine, and nondepolarizing muscle relaxants will also decrease muscle rigidity.
    3. Anesthetic implications. The exact relationship between NMS and malignant hyperthermia is unclear. Some patients with a history of NMS may be at risk for malignant hyperthermia, and a conservative approach may be warranted (eg, avoidance of known triggering agents). Patients with NMS must be appropriately monitored for malignant hyperthermia during all anesthetics (eg, temperature and end-tidal carbon dioxide). They should not be pretreated with dantrolene.