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CPT deficiency and
malignant hyperthermia |
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--Kirk Hogan, M.D. |
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 Malignant hyperthermia is a syndrome of muscle destruction, high heart rate, acidosis and often, but not always, high fever or hyperthermia. It is triggered in susceptible individuals on exposure to two types of commonly used anesthetic drugs. The first class of drugs includes those with an odor that the patient breathes to remain asleep: halothane, isoflurane, sevoflurane and
desflurane. The second class of drugs are depolarizing muscle relaxants.Succinylcholine is the only one in widespread use. The antidote drug Patients who carry a genetic predisposition to these drugs are potentially at risk of death during surgery unless the episode is detected early and the antidote dantrolene is given immediately. Genetic origins Because the disorder is often inherited, investigators have searched for clues in patients’ DNA to explain why the reaction happens and to one day determine who is at risk prior to anesthesia. Today about half of the genetic mutations responsible for malignant hyperthermia are known to occur in one of two proteins within the muscle cells called calcium channels. These channels normally release calcium from storage sites so that muscles can move properly. Anesthetic drugs also cause a release of calcium from normal channels, but in the presence of a mutation, huge increases in calcium release may start the malignant hyperthermia cascade. Discovery of the remaining 50% of the mutations is anticipated in the next several years. Who gets malignant hyperthermia? Malignant hyperthermia occurs in two types of patients:
those with no other recognized muscle problem.
those with clear-cut muscle disease even without anesthesia.It may be that these conditions simply represent different mutations in the same genes, with the mutations causing the least effect only detected upon exposure to anesthetic drugs. In either case, if a patient is known to be at risk before surgery, it is absolutely life-saving for all caregivers to be aware of the possibility, since appropriate monitoring and anesthetics of equal safety, patient satisfaction, and zero malignant hyperthermia risk may then be selected. CPT II deficiency and malignant hyperthermia Several cases resembling malignant hyperthermia have been reported in patients with CPT deficiency. In one, kidney shut down was caused by accumulation of myoglobin after muscle destruction. More recently, a malignant hyperthermia event in childhood was associated with a mutation in the CPT II gene . Although this patient had decreased CPT II enzyme activity, there were no symptoms in the absence of anesthesia. It appears that a deficiency of CPT II, but perhaps not CPT I, is the risk factor, since palmitoylcarnitine which accumulates in CPT II deficiency is able to open the calcium channels on its own. In fact, this may be the same mechanism by which CPT II deficiency causes muscle problems during other forms of stress and exercise. Advice for CPT II deficiency patients Much work remains before reaching a full understanding of these chemical changes. However, two recommendations for patients with CPT deficiency are warranted based on present knowledge.
First, patients with CPT deficiency (especially CPT II) must be considered susceptible to malignant hyperthermia and must not
receive the trigger drugs listed above. Second, since it is not always possible for someone needing emergency anesthesia and surgery to provide a good history (for example after a car accident involving a blow to the head), patients with CPT deficiency should wear medic alert bracelets or necklaces at all times. |
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| Dr. Hogan is an anesthesiologist at the University of Wisconsin. His research over the past ten years has focused on the genetic basis for malignant hyperthermia. | |
References: Katsuya H et al. Anesthesiology 1988 68:945-948 Vladutiu GD et al. Am J of Human Genetics 1998 63:A5-20 el-Hayek R et al. Biophysical Journal 1993 65:779-789 |
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links: Coping with anesthesia  MDA Quest article about the effects of anesthesia in neuromuscular disorders. Malignant hyperthermia UCLA department of anesthesiology pages on MH. Malignant Hyperthermia Association of the US Anesthesia protocol for cases of MH susceptibility. The antidote, dantrolene sodium Scroll down to the question and answer section: How does dantrolene work? How much should be kept in stock? etc. Mitochondrial myopathies and anesthetic complications Article from the University of Minnesota Center for Muscle and Muscle Disorders. Malignant hyperthermia and associated disorders Another article from the University of Minnesota. Malignant hyperthermia tutorial Detailed tutorial for medical students and physicians created by the department of anesthesia at the University of Basel, Switzerland. 
To see a muscle slide of malignant hyperthermia, visit In
graphic detail. To for more about
malignant hyperthermia and anesthesia, visit Double
take and Same difference.
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In MH-susceptible
people, muscle cells react in an unusual way to some of the
most commonly used drugs in the operating room. Inside these
cells, a molecular gate opens and stays open, allowing an
excessive and uncontrolled release of calcium. This excessive
calcium release causes muscles to contract continuously and
generates a massive amount of heat, enough to disrupt almost
every body process.
