Maligmant Hyherthermia What is new in Detection and treatment

1. Maligmant HyherthermiaWhat is new in Detection and treatment R3 Jung Jun Young

2. Clinical Presentation • Current inhalation anesthetics : slow onset of MH episode • Succinylcholine : make episode severe • Unexplained inc. of CO2 production as a consequence of elevated intracellular Ca2+ in muscle • Rhabdomyolysis • Acute episode of MH in common in male • Large muscle bulk and recent exercise are common in acute episode • Temp. monitoring : extremely important • core temp. elevation 의 기간이 morbidity와 연관됨 • MH Hotline : #1-800-644-9737

4. MH like symptoms can occur without exposure to anesthetic drugs - associated with exercise • Non anesthetic drug-induced rhabdomyolysis with underlying abnormality of muscle function • Exercise induced rhabdomyolysis 에서도 critical temp. 를 빨리 낮춰주는것이 중요 • Myoglobinuria 있으면 renal failure 막기위해 alkaline urine flow 증가시켜준다

7. Definitive Evaluation • Emergency Tx 후 potential myopathy에 대한 definitive diagnosis 필요 • Refer to Malignant Hyperthermia Diagnostic center (2 centers in Canada, 6 in USA) • Muscle contracture testing • MH 증상을 보인 환자에서 MH Negative (MHN)로 판명되는 경우가 많기 때문에 further evaluation 을 시행하는 것이 중요 • Significant muscle contracture -> it may contain mutation that is recognized to be causative for MH • Contracture test에서 MH Susceptible (MHS)로 판명된 pts에서 mutation이 identify된 경우 family member에 대해 contracture test 전에 genetic evaluation 시행 - MH causative familial mutation 발견되면 contracture test 시행하지 않고 MHS로 진단 - familial mutation 없는 경우 contracture test 시행 • The Dx of MHN can be made only by a negative contracture test result

8. Genetics of Malignant Hyperthermia • Ryanodine receptor gene(RYR1) - On chromosome 19q13.2 - Major locus of MHS • Other loci : CACNA1S gene • Current European MH group(EMHG) guidelines recognize 23 causative RYR1 mutations -mutation result in altered calcium control in muscle • Entire RYR1 gene에 대한 study에서 MHS로 진단된 환자의 50%이상에서 RYR1 mutation이 identify • Positive caffeine halothane contracture test 환자에서 3 ‘hot spot’에 대한 genetic screening 검사한 경우 23%에서만 mutation 발견됨 • Most frequent mutations : amino acid changes of Arg163Cys, Arg614Cys and Gly2434Arg in RYR1 axons 6, 17 and 45

9. Alternative tests of MH susceptibility? • Many alterntive test have been proposed • Microdialysis : can separate MHS from MHN patients, but require specialized equipment • Repetitive nerve stimulation : less invasive, but require anesthesia of some kind • RYR1 is expressed on β lymphocyte and in MHS pts these cells respond differently than normal to RYR1 agonists - Similar tests of lymphocytes might to be able to identify many MHS patients

10. Treatment • Rapid Tx with Dantrolene, elimination of triggering agents, active cooling and aggressive supportive care • Frequent cause of death : severe coagulopathy, failure to resuscitation from hyperkalemic cardiac arrest • Initial dantrolene 투여 24시간 내에 25%에서 MH relapse • At least 1mg/kg of dantrolene iv. every 6 hrs after initial Tx • Initial Tx 시 dantrolene average dose 는 ~2.5mg/kg 이지만 효과적인 치료위해 10mg/kg까지 필요로 하기도 함

12. m/c Cx after Dantrone adm : muscle weakness • In extreme case, positive pr. Ventilation may be required • ~25%에서 weakness 보고됨 • ~11%에서 phlebitis 보고됨 • Mannitol, 3g in each 20mg vial of dantrolene, can initiate a compartment synd