For patients at similar risk to those in this study, this leads to a positive predictive value of 80% and negative predictive value of 100%. This method may provide a suitable alternative to more invasive techniques. A 2002 study examined another possible metabolic test. In this test, intramuscular injection of caffeine was followed by local measurement of the pCO2; those with known MH susceptibility had a significantly higher pCO2 (63 versus 44 mmHg). The authors propose larger studies to assess the tests suitability for determining MH risk. Genetic testing
Genetic testing is being performed in a limited fashion to determine susceptibility to MH. In people with a family history of MH, analysis for RYR1 mutations may be useful. Criteria
A 1994 consensus conference led to the formulation of a set of diagnostic criteria. The higher the score (above 6), the more likely a reaction constituted MH:
Respiratory acidosis (end-tidal CO2 above 55 mmHg/7.32 kPa or arterial pCO2 above 60 mmHg/7.98 kPa)
Heart involvement (unexplained sinus tachycardia, ventricular tachycardia or ventricular fibrillation)
Metabolic acidosis (base excess lower than -8, pH <7.25)
Muscle rigidity (generalized rigidity including severe masseter muscle rigidity)
Muscle breakdown (CK >20,000/L units, cola colored urine or excess myoglobin in urine or serum, potassium above 6 mmol/L)
Temperature increase (rapidly increasing temperature, T >38.8 °C)
Other (rapid reversal of MH signs with dantrolene, elevated resting serum CK levels)
Family history (autosomal dominant pattern)

Prevention
In the past, the prophylactic use of dantrolene was recommended for MH-susceptible patients undergoing general anesthesia.
Some examples of drugs that dont cause MH include local anesthetics (lidocaine, bupivacaine, mepivacaine), opiates (morphine, fentanyl), ketamine, barbiturates, nitrous oxide, propofol, etomidate, and benzodiazepines. The nondepolarizing muscle relaxants pancuronium, cisatracurium, atracurium, mivacurium, vecuronium and rocuronium also do not cause MH.There is mounting evidence that some individuals with malignant hyperthermia susceptibility may develop MH with exercise and/or on exposure to hot environments. Genetics
Malignant hyperthermias inheritance is autosomal dominant with variable penetrance. The defect is typically located on the long arm of chromosome 19 (19q13.2) involving the ryanodine receptor. More than 25 different mutations in this gene are linked with malignant hyperthermia. These mutations tend to cluster in one of three domains within the protein, designated MH1-3. MH1 and MH2 are located in the N-terminus of the protein, which interacts with L-type calcium channels and Ca2+. MH3 is located in the transmembrane forming C-terminus. This region is important for allowing Ca2+ passage through the protein following opening.Chromosome 7q and chromosome 17 have also been implicated. It has also been postulated that MH and central core disease may be allelic and thus can be co-inherited. Pathophysiology
Disease mechanism
In a large proportion (50–70%) of cases, the propensity for malignant hyperthermia is due to a mutation of the ryanodine receptor (type 1), located on the sarcoplasmic reticulum (SR), the organelle within skeletal muscle cells that stores calcium. RYR1 opens in response to conformational changes in the L-type calcium channels following membrane depolarisation, thereby resulting in a drastic increase in intracellular calcium levels and muscle contraction.