MALIGNANT HYPERTHERMIA

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Malignant Hyperthermia: Etiopathology,diagnosis and treatment.

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MALIGNANT HYPERTHERMIA

  1. 1. Malignant Hyperthermia Dr. Naveen Kumar Gaur 2nd Year Resident Dept.of Anaesthesiology, Govt. Medical College & Sir T. Hospital, Bhavnagar(Gujarat)
  2. 2. Definition • Uncommon, life-threatening, pharmacogenetic, hypermetabolic disorder of the skeletal muscle triggered by inhalation agents and succinylcholine.
  3. 3. Genetics • Its an autosomal dominant trait. • Gene located on19th chromosome (19q11.2-13.2). • In most cases(>50%) MH is caused by defect in the ryanodine receptor(RyR1). (Release of calcium from SR) • Other chromosomes involved are – - 17q11.2-q24 – altered Na channel functioning. 7q21.1 – altered Dihydropyridine receptors(DHPR) – voltage sensors for RyR1.
  4. 4. Epidemiology • Usually occurs in children & young adults. (incidence highest in 1st three decades of life, but cases reported at extremes of ages) • Overall incidence rate during GA1 in 3000 – 15,000 children 1 in 50,000 – 100,000 adults • Geographical variation- more prevalent in certain areas of North America. • Male = Female • Mortality reduced from 70% to <5%(after dantrolene)
  5. 5.  Definite association: central core diseaseautosomal dominant congenital myopathy. (common gene RyR1 mutation)  Possible association: Duchene, Becker, KingDenborough, other myopathies. (Pts with Duchene's or Becker’s dystrophy are at risk for hyperkalemic cardiac arrest with succinylcholine or other MH triggering agents, but this is not MH.  Coincidental association: Neuroleptic Malignant Syndrome, Heat Stroke, etc
  6. 6. Porcine Stress Syndrome • MH like syndrome in certain breeds of swine. • Presentation - ↑ metabolism, acidosis, fever, rigidity & death. • Triggered by – separation, shipping condition, weaning, fighting, coitus, preparation for slaughter, etc. • This can be induced in stress susceptible swine by administering halothane & succinylcholine. • Cause – single mutation in RyR1.
  7. 7. Pathophysiology • MH is an inherited disorder of the skeletal muscle system in which a defect in the calcium regulation is expressed by exposure to triggering anesthetic agents → intracellular hypercalcemia. • The ryanodine receptors(RyR1) modulate calcium release from the channels in the SR. • ↑ in concentration of calcium in cells (upto 500 folds)
  8. 8. - Actomysin cross-bridging - Sustained muscle contraction - Rigidity ↓ - ↑ oxygen consumption - ↑ CO2 and heat production(hyperthermia) - depletion of ATP stores - lactic acid(Acidosis) - marked increase in - myoglobin - creatine kinase - potassium. • Cells damaged due to membrane instability.
  9. 9. Identifying Susceptible Patients Muscle Contracture Test • Caffeine Halothane Contracture Test(CHCT) • For patients having H/O MMR. • Gold Standard. • Requires 3-4 inch muscle biopsy taken from thigh(vastus muscle) under GA or LA. • Protocols – 1. North American MH group – abnormal contracture to either Halothane or Caffeine labels pt. as MH susceptible. 2. European MH group – abnormal contracture to both Halothane & Caffeine labels pt. as MH susceptible. • 97-99% sensitivity, false negatives are rare. • 78-94% specificity.
  10. 10. Genetic Testing • Involves isolation of DNA from patient (blood, muscle cells, or other tissue sample) • RYRI (ryanodine receptor) found, there are currently 29 MH causative RYRI mutations. • Presence of causative mutation in RYRI gene is diagnostic for MH susceptibility. • Sensitivity based on population selected and methodology of testing utilized.
  11. 11. MH Triggers • Volatile anesthetics - Ether - Halothane - Sevoflurane - Desflurane - Isoflurane - Enflurane • Depolarizing muscle relaxants - Succinylcholine
  12. 12. Nontriggering drugs for MH • • • • • • • • • • • Barbiturates Propofol Benzodiezepins Opioids Nitrous oxide Non depolarizing muscle relaxants Anticholinergics Anticholinesterases Sympathomimetics Local anaesthetics Clonidine,dexmedetomidine
  13. 13. Clinical Features
  14. 14. • Early – - Clinical signs – - Masseter spasm. - Tachypnea(in spontaneously ventilating pt). - Tachycardia. - Rapid exhaustion of soda lime. - Irregular pulse. - Change in monitored variables – - ↑ in minute ventilation. - ↑ in EtCO2 - Dysrythmia with peak T wave. - Biochemical changes – - ↑ in PaCO2 (100-200 mmHg) - Acidosis(pH 7.15-6.8) - Hyperkalemia.
  15. 15. • Intermediate – - Clinical signs – - Warm skin(temp↑ @ 0.5 C every 15 minutes and reaching levels as high as 46 C.) - Cyanosis. - Dark blood on surgical site. - Dysrythmia. - Change in monitored variables – - ↑ in core body temp. - ↓ Hb saturation.
  16. 16. • Late - Clinical signs – - Generalized skeletal muscle rigidity. - Prolonged bleeding. - Dark urine. - Irregular heart rate. - Biochemical changes – - ↑ in s. creatine kinase level. - Myoglobinuria. - Hyperkalemia.
  17. 17. • Late complications(if MH untreated) - DIC(due to release of thromboplastin secondary to cellular destruction) - Pulmonary edema. - ARF. - CNS damage – Blindness - Seizures - Coma - Paralysis
  18. 18. Treatment • Etiologic treatment – - Inj. Dantrolene 2-3 mg/kg iv bolus, followed with repeat dose every 5-10 min to maximum dose upto 10mg/kg. - To prevent recrudescence – Inj. dantolene 1mg/kg every 6 hrs for 48-72 hrs.
  19. 19. • Symtomatic treatment – - Immediate termination of inhaled anaesthetic & conclude surgery. - Hyperventilation with 100% oxygen. - Initiate active cooling – - surface cooling. - gastric & bladder lavage with iced saline. - iced saline 15 mg/kg iv every 10 minutes. (discontinue cooling when temp falls to 38 C)
  20. 20. - Correct metabolic acidosis –Inj. Soda bicarb 1-2 mEq/kg iv according to blood pH. - Maintain UOP – Hydration - Mannitol(0.25 mg/kg) - Furosemide(1mg/kg) - Treat cardiac dysrythmia(Loxicard 1.5mg/kg) - Monitoring of UOP, ABG, S.electrolytes.
  21. 21. Anaesthetic management • Regional anaesthesia- Acceptable choice(both esters and amides can be used) • Dantrolene prophylaxis – - if past H/O MH – Inj. Dantrolene 2-4mg/kg iv over 10-30 min. just prior to induction. - Catheterize patient, as drug contains mannitol (to make drug isotonic). - Large doses may cause – nausea, vomiting, diarrhea, blurred vision, skeletal muscle weakness(post op monitoring is must)
  22. 22. • Drug selection – - Keep preparations to treat MH. - Good sedation. - Avoid triggering agents. - Avoid CCB with dantrolene, may cause hyperkalemia and myocardial depression. • Anaesthesia machine – - “Dedicated” anaesthesia machine preferred(never been used to deliver volatile anaesthetics). - Conventional machine with – - disposable breathing circuits. - fresh soda lime. - no vaporizers. - continues flow of O2 @ 10 L/min for 10-60 minutes before using for MH susceptible patient.
  23. 23. Differential Diagnosis 1. Hyperthyroidism- similar symptoms, but blood gas abnormality occurs gradually. 2. Pheochromocytoma – marked BP swings. 3. Malignant neuroleptic syndrome – usually associated with use of neuroleptic/antipsychotic drugs. 4. Cocaine intoxicity – similar to MNS. 5. Heat stroke – outside the OT. 6. Metastatic carcinoid – similar to Pheochromocytoma. 7. Sepsis – usually ABG normal.
  24. 24. Dantrolene • A skeletal muscle relaxant(hydantoin derivative) • Blocks RyR1 receptors, thus block the calcium release. • T1/2 = 4-8 hrs. • Metabolized in liver. • Side effects – weakness, dizziness. • Each vial of dantrolene contains – - 20 mg dantrolene sodium. - 3000 mg mannitol(to make solution isotonic. - Sodium hydroxide(to keep pH near 9.5)
  25. 25. Thank you…

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