PRACTICE RECOMMENDATIONS
• Suspect malignant hyperthermia (MH) if a patient has night sweats, cramping, mottled skin, low-grade fever, and excessive sweating, or has elevated creatine kinase and rhabdomyolysis on lab studies. B
• Make sure patients and their family members know that MH is life threatening, familial, and can even occur in patients whose previous experiences with anesthesia have been uneventful. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
You are asked to perform a preoperative evaluation of a 6-year-old boy who is due to have a tonsillectomy. The family history reveals that his father had an episode that sounds like malignant hyperthermia (MH). Also, a paternal uncle experienced a high fever and almost died after undergoing anesthesia. The boy’s parents tell you they took the boy to a pediatrician, who did a “blood test” for MH. They hand you a written report of an enzyme-linked immunosorbent assay, which tested negative for an allergy to succinylcholine.
Has this child been adequately screened for MH?
If you answered No, you are correct. The review that follows explains why.
The “disease of anesthesia”
MH is a pharmacogenetic disease process that occurs when predisposed individuals are exposed to certain triggering agents—specifically, anesthetics. Succinylcholine and all potent inhalational anesthetic agents have been implicated (TABLE 1). Most episodes occur in the intraoperative period.
MH is a familial disease and follows an autosomal dominant pattern, but with incomplete penetrance. Surprisingly, the disease was not described until 1961, when Denborough et al reported a string of anesthetic-related deaths in a family.1,2 A similar condition was described in pigs in 1966.3 This condition, porcine stress syndrome, was noted during research in which pigs had received succinylcholine. This syndrome has become the animal model for the study of MH.4,5
Over time, this condition came to be known as malignant hyperthermia because a rapid rise in temperature was a common feature in all reported cases. Additional possible signs and symptoms include skin mottling, arrhythmias, elevated creatine kinase (CK), and rhabdomyolysis, among others (TABLE 2).
Associated conditions. MH may occur with any condition requiring intervention with anesthesia. It was once believed that strabismus and MH were linked, but this assumption was based on a statistical error related to an increased number of surgical procedures in children with strabismus. Currently, a propensity toward MH seems associated only with rare myopathic conditions such as central core disease, hypokalemic periodic paralysis, Evans myopathy, and King-Denborough syndrome.6 Precise genetic mapping will determine what, if any, relationship there is between these processes and MH.
TABLE 1
Triggering and nontriggering anesthetic agents
| Triggering agents | Nontriggering agents |
|---|---|
| Succinylcholine (most common) | Barbiturates |
| Desflurane | Benzodiazepines |
| Halothane | Ketamine |
| Isoflurane | Local anesthetics |
| Sevoflurane | Nitrous oxide |
| Nondepolarizing muscle relaxants | |
| Opioids | |
| Propofol | |
| Adapted from: Barash PG, et al, eds. Clinical Anesthesia. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2009. | |
TABLE 2
Signs and symptoms of malignant hyperthermia
| Arrhythmias |
| Coagulopathy |
| Elevated creatine kinase |
| Elevated temperature |
| Hypercarbia |
| Hyperkalemia |
| Increased oxygen consumption |
| Masseter muscle spasm |
| Metabolic acidosis |
| Muscle rigidity |
| Rhabdomyolysis |
| Skin mottling |
| Tachycardia |
| Tachypnea |
| Adapted from: Barash PG, et al, eds. Clinical Anesthesia. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2009. |
Awake triggering: Similar disorder without anesthesia
Since 1980 there have been several reports of “awake triggering” in genetically predisposed individuals, whereby stressful conditions alone unrelated to general anesthesia cause MH.7-10 Often, the presenting condition has been heat-stroke, but other symptoms are also common, such as rhabdomyolysis, increased CK, muscle pain, and cardiovascular collapse.11 Relatives of those with a history of MH have also exhibited chronic muscle pain or chronic CK elevation. All of these people, when tested, have had a positive reaction to the caffeine-halothane contracture test (CHCT), which is the gold standard for confirming MH.12
The Malignant Hyperthermia Association of the United States (MHAUS) lists signs and symptoms that accompany awake triggering on its Web site, www.mhaus.org. They include heat sensitivity, night sweats, cramping, mottled skin, low-grade fever, and excessive sweating.
Should such findings—especially elevated CK and rhabdomyolysis—come to your attention by a patient’s report or during physical examination, consider further workup for MH.
How MH develops
MH occurs because of a defect in the ryanodine receptor, RYR1. This receptor is responsible for intracellular calcium release by its mediation of the sarcoplasmic reticulum. RYR1 is found in all skeletal muscle.13 During an episode of MH, exposure to the triggering agent causes intracellular calcium release by the sarcoplasmic reticulum and sustained skeletal muscle contractions and rigidity. Increased oxygen consumption occurs, and this hypermetabolic state leads to hypercarbia, severe metabolic acidosis, tachycardia, arrhythmias, hyperkalemia, and elevated temperature. Rhabdomyolysis and elevations in CK also occur because of skeletal muscle breakdown.
How to treat this medical emergency