Chapter 87

1. Malignant hyperthermia (MH) was first described in 1962 in a case report that also suggested an inherited basis for the syndrome.

2. Skeletal muscle is the primary target tissue in MH. A laboratory diagnostic test for MH was developed using the enhanced contracture response to caffeine and halothane in muscle strips from MH patients. Studies using these tests suggest that the cellular mechanism responsible for MH is a derangement in calcium regulation.

3. No convenient minimally invasive laboratory test for MH susceptibility is yet available. Halothane and caffeine contracture assays remain the most reliable tests.

4. Molecular genetic tests based on identification of mutations in the RYR1 and CACNA1S genes can confirm the diagnosis of MH susceptibility.

5. A negative screen of the RYR1 and CACNA1S genes does not rule out MH susceptibility.

6. The immediate cause of an MH crisis appears to be a sudden increase in the concentration of myoplasmic calcium, thought to be triggered by inhalational anesthetic or depolarizing muscle relaxant interactions with the sarcoplasmic reticulum (SR).

7. All potent halogenated anesthetics and depolarizing muscle relaxants are capable of triggering an MH reaction, but an MH event does not always occur with each exposure to triggering anesthetic agents, even in persons subsequently found to be MH susceptible. This situation reflects the variable expression and penetrance of the gene mutations.

8. Time of onset of a fulminant episode of MH is unpredictable, varying from minutes to within several hours of induction; it may even occur in the recovery room.

9. The earliest signs of MH are hypercarbia, sinus tachycardia, and masseter muscle rigidity (MMR).

10. Laboratory signs of MH may include increased Paco2, metabolic and/or respiratory acidosis, hyperkalemia, increased creatine kinase (CK), myoglobinemia, and myoglobinuria.

11. In 1979, dantrolene, a drug that decreases skeletal myoplasmic Ca2+, was approved for clinical use by the Food and Drug Administration; this was a major advance in the treatment and management of MH.

12. A very low mortality rate from MH can be achieved by prompt recognition of the clinical situation, ready access to supplies necessary for treatment, and initiation of appropriate therapeutic measures starting with dantrolene 2.5 mg/kg intravenously.

Malignant hyperthermia (MH) is a dominantly inherited skeletal muscle disorder that predisposes susceptible individuals to a potentially fatal reaction upon exposure to potent volatile anesthetics and/or succinylcholine. In some individuals, MH-like reactions can also be triggered by high environmental temperatures and stress in the absence of anesthetics.1 Fulminant MH episodes apparently result from dysregulation of intracellular Ca2+, causing a rapid and sustained rise in myoplasmic Ca2+. Molecular genetic studies have identified mutations in the ryanodine receptor type 1 gene (RYR1), encoding the skeletal muscle Ca2+ release channel, to be a major cause for MH. However, MH is known to be a heterogeneous disorder, as mutations in RYR1 account for only 70% of all MH cases. There are also a few cases attributed to abnormalities in the CACNA1S gene, encoding the α1-subunit ...

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