malignant hyperthermia anaesthesia point of view

malignant hyperthermia

1. MALIGNANT HYPERTHERMIA By: Nabilah Athirah Binti Mohd Sazali

2. CONTENT Introduction Incidence Pathophysiology & pharmachogenetics Clinical manifestation Management

3. INTRODUCTION Malignant hyperthermia (MH) is a subclinical, potentially fatal pharmacogenetic disorder manifests initially as skeletal muscle hyper-metabolism and sustained contraction , but which secondarily affects all organs when susceptible individuals are exposed to triggering agents - haloalkane anesthetics  ex halothane, sevoflurane, desflurane and the depolarizing muscle relaxant

4. INCIDENCE incidence of malignant hyperthermia is unknown the incidence during general anesthesia is estimated to range from 1 : 5,000 to 1 : 50,000-100,000 in individuals However, the true number of individuals with MHS is likely to be much greater, because many individuals with MHS are never anesthetized,  the estimated prevalence of MHS is thought to be approximately 1 in 50,000 or less. However, according to the results of recent molecular genetic studies, the estimated genetic prevalence may be up to 1 : 2,000-3,000 because MHS is inherited as an autosomally dominant trait

5. occurs more frequently in males than females mo re commonly in children and young adults with the mean age of 18.3 years In a study done in NewYork , the estimated prevalence of MH for males was 2.5-4.5 times the rate for females, and the median age at presentation was 22 years

6. PATHOPHYSIOLOGY

7. SERCA-pumps -  (sarco-endoplasmic reticulum Ca 2+  ATP- asis ), reduces myoplasmic Ca 2+  ( responsible for relaxation of the muscle) S mall amount of Ca 2+  also enters the mitochondrial matrix to activate the mitochondrial respiratory chain and increase aerobic ATP production  Some Ca 2+  is extruded in the extracellular matrix by plasma membrane (PM) Ca 2+  ATPases (PMCA), causing a slight decrease in the SR Ca 2+  content

8. Hypoxaemia failure of membrane integrity with leakage of muscle cell contents (including electrolytes, myoglobin, CK into the circulation

9. Clinical findings

10. DIAGNOSIS Despite the autosomal dominant pattern of inheritance, genetic testing is not a definitive diagnostic tool. The gold standard diagnostic test is muscle contracture test in-vitro contracture test (IVCT) by European Malignant Hyperthermia Group (EMHG) vs. the caffeine-halothane contracture test (CHCT) by the North American Malignant Hyperthermia Group (NAMHG)  this test is invasive & expensive Alternative: molecular genetic testing

11. MANAGEMENT mortality rates of MH dramatically decreased from 70-80% to 10% after an introduction of dantrolene sodium recent mortality is estimated to be less than 5% with early detection of MH episode using capnography, prompt use of the drug dantrolene, and the introduction of diagnostic testing

12. MANAGEMENT Preoperative evaluation standard anaesthetic assessment should be extended to include direct questioning for a history of rhabdomyolysis , which is more common in MH-susceptible individuals than the general population.  A small minority of MH-susceptible patients have an associated clinical myopathy

13. BJA, Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group, published in October 29, 2020 Malignant hyperthermia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867813/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506847/#:~:text=Generally%2C%20the%20estimated%20prevalence%20of,trait%20%5B3%2D5%5D.