A review on Malignant Hyperthermia: Epidemiology, etiology, risk factors, diagnosis, clinical management and treatment modalities

Abstract

Malignant hyperthermia (MH) is a skeletal muscle pharmacogenetic disorder that manifests as a hypermetabolic response to powerful volatile anaesthetic gases like halothane, sevoflurane, desflurane, isoflurane, and the depolarizing muscle relaxant succinylcholine, as well as stressors like vigorous exercise and heat in human body. Anesthetics with an MH reaction rate vary from 1:10,000 to 1:250,000. On the other hand, the incidence of genetic anomalies might be as high as one in 400 people. Humans, specific pig breeds, dogs, and horses are all affected by MH. Hyperthermia, tachycardia, tachypnea, increased carbon dioxide generation, increased oxygen demand, acidosis, hyperkalaemia, muscular stiffness, and rhabdomyolysis are all typical indications of MH, all of which are associated with a hypermetabolic response. The condition is likely to be fatal if untreated. An early diagnostic indication is a rise in end-tidal carbon dioxide despite enhanced minute ventilation. Humans inherit the condition in an autosomal dominant form, whereas pigs inherit it in an autosomal recessive form. The pathophysiologic alterations are caused by an uncontrolled surge in myoplasmic calcium, which triggers biochemical pathways associated to muscle activation. A deficiency in the ryanodine receptor is the most common cause of the condition. The RYR1 gene, which is found on chromosome 19q13.1, has over 400 variations, at least 34 of which are linked to MH. In CACNA1S, less than 1% of variations have been discovered, although not all of them are causative. The in vitro contracture response of biopsied muscle to halothane, caffeine, and in certain centres, ryanodine and 4-chloro-m-cresol is used in diagnostic testing. The discovery of the genetic alterations has led to the development of DNA testing for MH susceptibility. Dantrolene sodium is a particular antagonist that should be provided in every setting where general anaesthesia is used. Because of a better knowledge of the clinical manifestations and pathophysiology of the disease, mortality has decreased from 80% thirty years ago to less than 5% in 2006.

Piktybinė Hipertermija: Farmakogenetika Ir Gydymas

“…Klinika. Ankstyviausi PH požymiai apima raumenų rigidiškumą, tachikardiją, nepaaiškinamą hiperkapniją, nuolatinį CO 2 didėjimą iškvėpimo pabaigoje ir pakilusią kūno temperatūrą [11][12][13]. Esant dviem ar daugiau iš šių požymių, PH tikimybė yra žymiai padidėjusi.…”

“…Simpatinės nervų sistemos suaktyvėjimas gali nulemti tachiaritmijas, hipertenziją ir fragmentišką cianozę [11]. Kūno temperatūra gali kilti iki 1 0 C per 5 minutes [3,11,12]. Generalizuotas raumenų rigidiškumas yra būdingas požymis, tačiau nėra stebimas visais PH pasireiškimo atvejais [3,11].…”

“…Tamsios spalvos šlapimas tipiniais atvejais rodo mioglobinuriją [11]. Dėl staigaus energijos atsargų išsekimo nekontroliuojamas hipermetabolizmas sukelia respiratorinę ir metabolinę acidozę, hiperlaktatemiją, hipoksemiją, hiperkapniją [12,13]. Besitęsianti miocitų nekrozė ir rabdomiolizė gali lemti gyvybei grėsmingą hiperkalemiją, o nekoreguojama mioglobinurija gali sukelti ūminį inkstų nepakankamumą.…”