October 12, 2005
Malignant Hyperthermia (MH) 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. The earliest findings are an increased production of carbon dioxide and signs of increases sympathetic nervous system activity.
Malignant Hyperthermia is typically a life threatening disease, also referred to as a syndrome, which occurs when a person with Malignant Hyperthermia susceptibility trait is exposed to triggering factors, which include most inhalational anesthetics (though not Nitrous Oxide), succinylcholine ( a muscle relaxant used during surgery) and rarely stress. Classic Malignant Hyperthermia is characterized by hypermetabolism, (increased oxygen consumption and increased carbon dioxide production) muscle rigidity, muscle injury, and increased sympathetic nervous system activity. Hypermetabolism reflected by elevated carbon dioxide Kay 2
production precedes the increase in body temperature. (http://www.mhaus.org)
In muscle contraction calcium is released into the cell as a key component in muscle contraction. In MH there is a problem with calcium reuptake. Intracellular calcium increases up 500 fold leading to substained muscle contraction. The cell incurs a severe oxygen debt, the constant demand for ATP leads to glycolysis and subsequent to lactic acidosis. Eventually this lead to membrane instability, cell rupture and rhabdomyolysis. (http://www.mhaus.org)
MH is important because it is a potentially fatal disorder. In April 2005 there was ground breaking research results in pioneering a new blood test for MH. (http://www.mhaus.org) In Sherburne NY after years of investigation a new era has opened for those affected by a life threatening inherited disorder MH. This new information for MH families comes in the form of long- awaited molecular genetic diagnostic test. It means patients and their families that have been uncertain about whether they have this potentially fatal disorder of anesthesia may now have a chance of discovering they DO have this risk by means of DNA analysis obtained from a blood sample.
Until the recent groundbreaking test for MH susceptibility has been the Halothane caffeine contracture test. In this test a small piece of muscle Kay 3
is obtained under regional or general anesthesia and while still viable is placed in a special solution and attached to a device which measures the force of contraction. The muscle strip is then exposed to either halothane or caffeine and the response measured. A response to halothane or a response to low concentrations of caffeine are considered diagnostic for malignant hyperthermia susceptible muscle. There are only nine Centers in the United States and Canada which perform biopsies where patients suspected of being MH can be evaluated and if indicated have a diagnostic biopsy performed. All biopsies must be performed at the diagnostic center since the muscle must be fresh when tested. As for the new DNA blood test there are only two Centers in the United Stated and Canada that perform the molecular genetic diagnostic testing. Which is a less invasive and less expensive then the cumbersome biopsy test. (http://firstname.lastname@example.org)
Treatment of MH involves on the one hand, the reversal of the primary disorder with dantrolene, and on the other, general resuscitative measures. Dantrolene acts by improving calcium dependent muscle...