[4]scientific advances in malignant hyperthermia

7/31/2019 [4]Scientific Advances in Malignant Hyperthermia

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John F. Hernandez, MSN, CRNA, Janet A. Secrest,PhD, RN, Linda Hill, CRNA, DNSc, S. Jack

McClarty, MD


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Introduction.

Background.

Diagnosis and managment of MH.

Genetic Basis.


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Malignant Hyperthermia (MH) is a potentially fataldisorder triggered by certain types of generalanesthesia.

Genetic basis recognized in the early 1990.

Diagnosis and genetic bases.

The mortality rate are app. 10% compared with 70

80% originally. This reduction is the result ofincreased awareness of the condition by anaesthetistsand improved standards of perioperative monitoring,together with the specific drug treatment, dantrolene.


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The first case was reported in1960, a fracture repair withgeneral anesthesia.

The familial history ofanesthesia-related deaths withthe use of ether.

A cooling bath with bloodtransfusion. 90 minutes to fullrecovery.

13 months later the patientsreturns for a calculus extractionunder spinal Anesthesia without

adversity. 10 relatives had similar clinical

experiences and presented withfever up to 43C, convulsions,and ultimately death.

The anesthesiologist concludedthat a genetic link existed amongthe family members.


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Malignant

Hyperthermia (MH)

Genetic basis, triggered byAnesthetics

Hypercarbia.

Increased metabolic state, lossof calcium homeostasis.

Hyperpyrexia.

Genetic linkagesitill not completely

understood.

RyR1

High level ofDioxide carbon High fever


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MH is typically associated with malfunctions in the, MH is especially a risk for patients with in the

receptor and who take hydrocarbon .

MH is the in muscles with excessiveoxygen consumption.

In MH,receptors are defective and

they release excessive Ca++which needs to be reabsorbed,this requires a lot of ATP.Excess mitochondrial oxidativephosphorylation cycles occurto generate this, leading toheat generation(hyperthermia).


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Unexplained increase in bothheart rate and carbon dioxide

Clinical features :

Hypercarbia

Tachycardia

Hyperthermia

Matabolic acidosis

Cyanosis

Spasm, rigidity, contracture Renal failure

Intravascular coagulopathy


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None of the features listed previously are unique, the diagnosisof malignant hyperthermia and the diagnosis can be difficult.


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Early DNA family studiesshowed linkage between theRyR1 gene on chromosome19q12-13.2 and MH.

Only 60% of European familieswith MH have been shown tohave linkeage to RyR1.

RyR1 is a large gene and over

100 mutations have been nowindentified, but only 22 haveevidence of functional activity.


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Attempts to identify all causal mutations haveresulted in the discovery of new RyR1mutation types


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Other chromosomal cause were suspected inpatients who lack de Ryanodine mutation.

Althoug MHS1 has been the only geneticcause of direct MH, The additional presenceof MHS3, MHS4, MHS5 mutations may interactin phenotype expression in some individuals.


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[4]scientific advances in malignant hyperthermia

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