Treatment
The current treatment of choice is the intravenous administration of dantrolene, the only known antidote, discontinuation of triggering agents, and supportive therapy directed at correcting hyperthermia, acidosis, and organ dysfunction. Treatment must be instituted rapidly on clinical suspicion of the onset of malignant hyperthermia.
Dantrolene is a muscle relaxant that appears to work directly on the ryanodine receptor to prevent the release of calcium. After the widespread introduction of treatment with dantrolene, the mortality of malignant hyperthermia fell from 80% in the 1960s to less than 10%. Dantrolene remains the only drug known to be effective in the treatment of MH.
Its clinical use has been limited by its low water solubility, leading to requirements of large fluid volumes, which may complicate clinical management. Azumolene is a 30-fold more water-soluble analogue of dantrolene that also works to decrease the release of intracellular calcium by its action on the ryanodine receptor. In MH susceptible swine, azumolene was as potent as dantrolene. It has yet to be studied in vivo in humans, but may present a suitable alternative to dantrolene in the treatment of MH.
Research in mouse models suggests that azumolene "is likely uncoupling the efficiency of a Ca2+-dependent RyR1 signal coupled directly or indirectly to the machinery." There may be two different pathways of store-operated calcium entry: one, RyR1-reliant and the other, RyR1-non-reliant (see Disease Mechanism section above for RyR1 description). Furthermore, elucidating earlier ideas on the pathogenesis of malignant hyperthermia, researchers point out that it may be "as much a syndrome of exaggerated Ca2+ entry as it is of exaggerated Ca2+ release."
Azumolene has also been shown to be as effective as dantrolene at preventing and reversing contracture in in vitro experiments with human skeletal muscle.
Read more about this topic: Malignant Hyperthermia
Famous quotes containing the word treatment:
“[17th-century] Puritans were the first modern parents. Like many of us, they looked on their treatment of children as a test of their own self-control. Their goal was not to simply to ensure the child’s duty to the family, but to help him or her make personal, individual commitments. They were the first authors to state that children must obey God rather than parents, in case of a clear conflict.”
—C. John Sommerville (20th century)
“I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrongdoing. Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course. Similarly, I will not give to a woman a pessary to cause abortion. I will keep pure and holy both my life and my art.”
—Hippocrates (c. 460–c. 370 B.C.)
“If the study of all these sciences, which we have enumerated, should ever bring us to their mutual association and relationship, and teach us the nature of the ties which bind them together, I believe that the diligent treatment of them will forward the objects which we have in view, and that the labor, which otherwise would be fruitless, will be well bestowed.”
—Plato (c. 427–347 B.C.)