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

Jack McClarty, MD

Oscar Leonardo Mosquera Dussan (2012).

Introduction. Background.

Diagnosis and managment of MH.

Genetic Basis.

Malignant Hyperthermia (MH) is a potentially fatal disorder triggered by certain types of general anesthesia. 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 of increased awareness of the condition by anaesthetists and improved standards of perioperative monitoring, together with the specific drug treatment, dantrolene.

The first case was reported in 1960, a fracture repair with general anesthesia. The familial history of anesthesia-related deaths with the use of ether. A cooling bath with blood transfusion. 90 minutes to full recovery. 13 months later the patients returns for a calculus extraction under spinal Anesthesia without adversity. 10 relatives had similar clinical experiences and presented with fever up to 43C, convulsions, and ultimately death.

The anesthesiologist concluded that a genetic link existed among the family members.

Malignant Hyperthermia (MH) Genetic basis, triggered by Anesthetics Genetic linkage sitill not completely understood.

Increased metabolic state, loss of calcium homeostasis.

Hypercarbia.

Hyperpyrexia.

RyR1

High level of Dioxide carbon

High fever

MH is typically associated with malfunctions in the Ryanodine receptor (RyR1), MH is especially a risk for patients with genetic disorders in the receptor and who take halogenated hydrocarbon inhaled anesthetics. MH is the unopposed consumption of ATP in muscles with excessive oxygen consumption.

In MH, receptors are defective and they release excessive Ca++ which needs to be reabsorbed, this requires a lot of ATP. Excess mitochondrial oxidative phosphorylation cycles occur to generate this, leading to heat generation (hyperthermia).

Unexplained increase in both heart rate and carbon dioxide Clinical features : Hypercarbia Tachycardia Hyperthermia Matabolic acidosis Cyanosis Spasm, rigidity, contracture Renal failure Intravascular coagulopathy

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

Early DNA family studies showed linkage between the RyR1 gene on chromosome 19q12-13.2 and MH. Only 60% of European families with MH have been shown to have linkeage to RyR1. RyR1 is a large gene and over 100 mutations have been now indentified, but only 22 have evidence of functional activity.

Attempts to identify all causal mutations have resulted in the discovery of new RyR1 mutation types

Other chromosomal cause were suspected in patients who lack de Ryanodine mutation.

Althoug MHS1 has been the only genetic cause of direct MH, The additional presence of MHS3, MHS4, MHS5 mutations may interact in phenotype expression in some individuals.