Malignant Hyperthermia Association of the

Malignant Hyperthermia Association of the United States reports that, "The sudden unexpected death of a healthy individual undergoing minor surgery is a tragedy almost beyond comprehension in this day of modern medical miracles. Yet this still happens to patients susceptible to malignant hyperthermia (MH)" (p. 2). These authorities emphasize as well that even when malignant hyperthermia is properly treated, it can still cause death or in rare cases, survivors may experience brain damage, failed kidneys, muscle damage or impaired function of other major organs (What is malignant hyperthermia?, 2007, p. 3).

The University of California at Los Angeles Department of Anesthesiology adds that, "Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle. Characteristically patients with this disease have no signs or symptoms except during an anesthetic. When exposed to inhalational anesthetics (those which are gases), muscle metabolism increases, and a series of signs and symptoms appear, which if left untreated can lead to death" (Malignant hyperthermia, 2007, p. 2). The etiology of malignant hyperthermia has been closely studied, but some issues remain unclear.

What is known is that, "There is a single gene that, when defective, predisposes an individual to develop alarmingly high temperatures (for example, 108°F) while undergoing a routine surgical operation under anesthesia. Deaths on the operating table from malignant hyperthermia are well-known but thankfully rare and treatable if detected immediately" (Milunksy, 2001, p. 9). In their recent study, "Uncoupling of ATP-Mediated Calcium Signaling," Cherednichenko, Chu, Goth and their colleagues (2006) report that, "The human RyR1 gene is highly polymorphic.

More than 60 single missense or deletional mutations have been closely linked to the pharmacogenetic disorders malignant hyperthermia and central core disease" (p. 1083). Furthermore, Armstrong, Atchinson, Audeskirk et al. (2000) note that a number of human disorders have been traced to mutations in the l subunit genes, including malignant hyperthermia.

These authors report that a diverse set of clinical syndromes is typically associated with mutations in the genes that encode the various calcium channel subunits; in some cases, the syndrome is caused by: (a) mutations in different genes [e.g., mutations in the ryanodine receptor (RYR1) or the [Alpha] 1S calcium channel cause malignant hyperthermia]; (b) in other cases, mutations in the same gene are associated with different clinical syndromes (i.e., FHM and EA-2 are both caused by mutations in the [Alpha] 1A calcium channel subunit) (Armstrong et al., 2000).

In addition, some anesthesia drugs trigger a sudden increase in the amount of calcium inside the skeletal muscle cells in malignant hyperthermia cases, a process that leads to excessive activation of the body's metabolism (Bogner, 2004).

This point is also made by Murray (1987), who reports that the symptoms of malignant hyperthermia, particularly hyperpyrexia and muscular rigidity, which were first described fully in 1962, is a pharmacogenetic myopathy (e.g., a reaction to halogenated, inhalational anesthetic agents and depolarizing muscle relaxants); physical and emotional stress have been cited as possible triggers for malignant hyperthermia (Murray, 1987).

According to this author, laboratory abnormalities in malignant hyperthermia include: (a) metabolic acidosis, (b) massive elevations in serum of muscle enzymes, - low levels of calcium or magnesium electrolytes, (d) tachycardia, (e) muscular rigidity, and (f) enzyme shifts (Britt, 1979; Levenson, 1985 cited in Murray, 1987 at p. 40). An individual's susceptibility to the condition can be diagnosed by an exaggerated response of muscle tissue when exposed to caffeine in vitro (Murray, 1987; Nehlig, 2004; Larch, 1989). References Armstrong, D., Atchison, W., Audesirk, G., Fletcher, C., Shafer, T., & Van Den Maagdenberg, a.R. (2000).

Calcium channels: Critical targets of toxicants and diseases. Environmental Health Perspectives, 108(12), 1215. Bogner, M.S. (2004). Misadventures in.