1 / 31

Malignant Hyperthermia

PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson. Malignant Hyperthermia. By: Charlotte Lin, Kathy Nguyen, Keisha Desa, Howard Pan. Outline. •Introduction •Symptoms and Diagnosis •Treatment and Prevention •Biochemical Mechanism •Conclusion. Introduction. What is MH? - Overview.

livingston
Télécharger la présentation

Malignant Hyperthermia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson Malignant Hyperthermia By: Charlotte Lin, Kathy Nguyen, Keisha Desa, Howard Pan

  2. Outline • •Introduction • •Symptoms and Diagnosis • •Treatment and Prevention • •Biochemical Mechanism • •Conclusion

  3. Introduction

  4. What is MH? - Overview • •Rare, inherited • •Defect in Ryanodine receptor • •Undiagnosed until exposure • to anesthesia • •Hypermetabolic Response

  5. What is MH? - Genetics •Autosomal dominant •Close to 100 mutations in the RYR-1 gene identified •Located on chromosome 19q13.1 •Ryanodine protein: N or C terminus •Result: Increased intracellular Calcium

  6. Symptoms and Diagnosis

  7. Early Symptoms Skeletal Muscle Rigidity

  8. Early Symptoms Very Fast Increase in Body Temperature (Hyperthermia)

  9. Early Symptoms Tachycardia – increased heart rate

  10. Other Early Symptoms • Muscle Spasms • Sweating • Tachypnea – increased breathing rate • Metabolic and Respiratory Acidosis and Cellular Ion Imbalances

  11. Late Symptoms Within minutes, the patient can die from cardiac arrest

  12. Late Symptoms Within hours, the patient can die from pulmonary edema or coagulopathy:

  13. Late Symptoms Within days, the patient can die from neurological damage or obstructive renal failure

  14. Summary of Symptoms

  15. Clinical Diagnosis • On average, it may take up to 3 anesthesia encounters before a MH episode is triggered • May happen during anesthesia or within the early post-op period (first few hours) • The primary indicative symptoms include: unexplained elevation of end-tidal carbon dioxide (ETCO2) concentration, muscle rigidity, tachycardia, acidosis & hyperthermia • Diagnosis is difficult because of the high degree of clinical variability in the order of the symptoms and the time of onset

  16. Clinical Diagnosis • In a 1994 conference, an international panel of 11 MH experts devised the following diagnostic scale:

  17. Treatment and Prevention

  18. Treatment of Acute MH Crisis • Discontinue triggering agents • Hyperventilation with 100% oxygen to lower end tidal CO2 and eliminate anesthetic from the body • IV admin of dantrolene • initial dose of 2.5mg/kg • repeat every 5 min until all symptoms subside • Cooling measures to reduce fever

  19. Management of Complications • Use bicarbonate to treat acidosis • Insulin with glucose to treat hyperkalemia • Beta blockers or lidocaine for arrhythmia and coagulopathy but not calcium channel blockers • Aggressive hydration to treat myoglobinuria

  20. Dantrolene • Muscle relaxant • Act on RyR1 and RyR3 direct to inhibit calcium release • Poorly water soluble • Alkaline preparation highly irritating • Drug-drug interaction with calcium channel blockers

  21. Prevention • Assess susceptibility • Anesthetic history of patient or family member • Caffeine-halothane contracture test • DNA testing • Preparation of anesthesia machine: • Remove vaporizers • Flush through the machine with 100% oxygen • Use a new breathing circuit

  22. Biochemical Mechanisms

  23. Biochemical Mechanisms • Most common mutation occurs in the Ryanodine Receptor (RyR) protein • - Other mutations exist • The job of RyR is to release Ca2+ from ER to cytosol • Presence of Ca2+ in cytosol initiate muscle contraction (excitation-contraction coupling) Ryanodine Receptor

  24. Biochemical Mechanisms Excitation-contraction coupling: - AP of neuron cause acetylcholine release - Acetylcholine bind to nicotinic receptors - Nicotinic receptors initiate end-plate potential (EPP) - End-plate potential cause RyR to release Ca2+ from endoplasmic reticulum

  25. Biochemical Mechanisms • Excitation-contraction coupling: • - Ca2+ causes muscles to contract • - Process is stopped when EPP is stopped and Ca2+ is removed from cytosol • Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) • Ca2+ pumps • Na+-Ca2+ exchanger

  26. Biochemical Mechanisms • RyR mutation: • - Leads to very sensitive RyR that release Ca2+ easily • - Frequent release of Ca2+ cause muscles to contract constantly • - High ATP requirement for muscles • Cross-bridge cycling • SERCA • Other Ca2+ pumps

  27. Biochemical Mechanisms Problems with high ATP requirement: -Mitochondrial activity pushed to the max • Intense heat production -Mitochondria cannot keep up with oxidative phosphorylation • Instead utilize glycolysis (lactic acid production) • Metabolic acidosis

  28. Biochemical Mechanisms • As a result: • - Body temperature increases rapidly • Enzymes won't function properly in body • Organ dysfunction • Muscle breakdown • Heart failure • Kidney failure • - Blood pH drops (metabolic acidosis) • Leads to coma

  29. Biochemical Mechanism • A word on general anesthesia induced MH: • - Still an active area of research • - Mechanisms are not yet fully understood

  30. Malignant Hyperthermia Summary • MH is a rare, autosomal dominant disorder with a mutation in a part of chromosome 19 coding for the Ryanodine receptor (RyR) gene causing RyR hypersensitivity • Diagnostic symptoms of MH include: skeletal muscle rigidity, hyperthermia and acidosis • Without clinical intervention, the patient will succumb as critical organ systems fail (cardiac arrest, pulmonary edema, neurological damage) • Hypersensitive RyR leads to Ca2+ leakage into cytoplasm from ER causing increased metabolism and continuous muscle contraction. • Hypermetabolic state of cells leads to increased body temperature and metabolic acidosis. • Steps to treatment: • 1. remove triggering agent • 2. hyperventilate • 3. IV administration of dantrolene • 4. cooling measure • 5. bicarbonate, glucose-insulin, hydration

  31. References • Larach M.G., Localio A.R., Allen G.C., Denborough M.A., Ellis F.R., Gronert G.A., Kaplan R.F., Muldoon S.M., Nelson T.E. & Ording H. (1994). A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 80(4), 771-9. • Maclennon, D. H & Phillips, M.S. (1992) Malignant hyperthermia. Science. 256 (5058), 789-794. • Rosenberg, H., Davis, M., James, D., Pollock, N. & Stowell, K. (2007) Malignant hyperthermia. Orphenet Journal of Rare Diseases. 2(21), 1-14. • The Pennsylvania Patient Safety Authority. (2008). Malignant hyperthermia: Is your facility prepared to treat this rare condition? Pennsylvania Patient Safety Authority. 5(3), 90-95. • Kim, D.-C. Malignant hyperthermia. Korean journal of anesthesiology 63, 391–401 (2012). • Halsall, P. J. & Hopkins, P. M. Malignant hyperthermia. Continuing Education in Anaesthesia, Critical Care & Pain 3, 5–9 (2003). • Fujii, J., Otsu, K., Zorzato, F., Leon, S. De, Khanna, V. K., Weiler, J. E., Brien, P. J. O., et al. (1991). Identification of a Mutation in Porcine Ryanodine Receptor Associated with Malignant Hyperthermia. Science, 253(5018), 448–451. • Hopkins, P. M. (2011). Malignant hyperthermia. Anaesthesia & Intensive Care Medicine, 12(6), 263–265. doi:10.1016/j.mpaic.2011.03.005 • Moyes, C., & Schulte, P. (2008). Principles of Animal Physiology (6th ed.). San Francisco, CA: Pearson Education Inc. • Tomarken, J. L., & Britt, B. a. (1987). Malignant hyperthermia. Annals of emergency medicine, 16(11), 1253–65. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3310764 • Bandschapp, O., & Girard, T. (2012). Malignant hyperthermia. Swiss medical weekly, 142. doi:10.4414/smw.2012.13652 • De Carvalho Correia, A. C., Silva, P. C. B., & Silva, B. A. D. (2012). Malignant hyperthermia: clinical and molecular aspects. Revista brasileira de anestesiologia, 62(6), 820–37. doi:10.1016/S0034-7094(12)70182-4 • Halsall, P. J., & Hopkins, P. M. (2003). Malignant hyperthermia. British Journal of Anaesthesia, 3, 5–9. doi:10.1093/bjacepd/mkg002 • Krause, T., Gerbershagen, M. U., Fiege, M., Weisshorn, R., & Wappler, F. (2004). Dantrolene--a review of its pharmacology, therapeutic use and new developments. Anaesthesia, 59(4), 364–73. doi:10.1111/j.1365-2044.2004.03658.x • Posenberg, H., Davis, M., James, D., Pollock, N., & Stowell, K. (2004, November). Malignant hyperthermia. Orphanat Encyclopedia. doi:10.4097/kjae.2012.63.5.391 • Statement, N., Audience, T., History, C., Statement, D., Objectives, L., & Writers, C. F. O. R. (2005). Lesson 248: PreAnesthetic Assessment of the Patient With Malignant Hyperthermia. Anesthesiology News, (December), 49–53. • Wappler, F. (2010). Anesthesia for patients with a history of malignant hyperthermia. Current opinion in anaesthesiology, 23(3), 417–22. doi:10.1097/ACO.0b013e328337ffe0

More Related