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Malignant Hyperthermia

Malignant Hyperthermia

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Malignant Hyperthermia

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  1. Malignant Hyperthermia (Anesthesia, n. d.) What you need to know

  2. What is it? • Malignant hyperthermia (MH) is a condition that is characterized by hyperthermia, tachycardia, tachypnea, increased CO2 production, increased O2 consumption, acidosis, muscle rigidity, and rhabdomyolysis • This condition is triggered by general anesthetic gases, succinylcholine, and more rarely stress, heat, or exercise • Occurs from once every 5,000 anesthesias to once every 50,000-100,000 anesthesias (Rosenberg, H., Davis, M. James, D., Pollock, N., & Stowell, K., 2007)

  3. What causes it? • Mutations on the ryanodine receptors (RYR1) on the sarcoplasmic reticulum in skeletal muscle cells respond adversely to triggering agents • Triggering agents include: inhaled general anesthetics, desflurane, enflurane, ether, halothane, isoflurane, methoxyflurane, sevoflurane, and succinylcholine (RL-0186, 2011) (PACKAGE LABEL.PRINCIPLE DISPLAY PANEL-250ML, 2013) (MHAUS, 2014)

  4. What causes it? • Triggering agents act on two sites on the ryanodine receptors of the sarcoplasmic reticulum in skeletal muscle cells • Both sites respond to Ca2+ levels • the A site opens Ca2+ channels on the SR and the I site closes Ca2+ channels • When these receptors have mutations associated with MH, the A sites become much more sensitive and the I sites become much less sensitive to triggering agents • This leads to Ca2+ channels on the SR opening more quickly and become very difficult to close (Yang, T., Ta, A. T., Pessah, I. N., & Allen, P. A., 2003)

  5. What causes it? (Revello, 2012) • Sustained high levels of Ca2+ cause sustained muscle contraction which requires more ATP from the body and the body enters a hypermetabolicstate

  6. How do we diagnose MH? • MH is difficult to diagnose due to variability in order and time of onset of signs of the condition • In the operating room, MH typically presents with an unexplained elevation of end-tidal CO2 levels, muscle rigidity, tachycardia, acidosis, hyperthermia, and hyperkalemia • Larach et al. have developed a clinical grading scale to determine MH susceptibility (Mitchell, 1978)

  7. MH Susceptibility Formulated by Larach et. al., this chart shows what providers look for when diagnosing MH (Rosenberg, H., Davis, M. James, D., Pollock, N., & Stowell, K., 2007)

  8. Diagnostic Tests • Currently, the main test is the in vitro contracture test (IVCT) with both the European Malignant Hyperthermia Group (EMHG) and North American Malignant Hyperthermia Group (NAMHG) both releasing protocols • In this test, muscle fibers are exposed to caffeine and halothane, two triggering agents • The IVCT test is expensive, subjects the patient to a surgical procedure to gather muscle fibers, and the results are not always accurate • EMHG protocols are 99% sensitive and 94% specific • NAMHG protocols are 97% sensitive and 78% specific • There is also a DNA test that identifies mutations associated with MH

  9. Precautions • Comprehensive histories are necessary to determine any potential risk of MH occurring during anesthesia administration • The Malignant Hyperthermia Association of the United States (MHUAS) details precautions that should be taken to ensure hospitals and surgical teams are prepared for an episode • MH carts stocked with necessary supplies should be available at all times • Anesthesia administration equipment should be prepared for patients who are known to be susceptible to MH • MHAUS sells a Mock Drill Kit which includes a video and materials to practice MH scenarios • MHUAS sells procedure manuals that provide step-by-step guides to dealing with an MH crisis

  10. MH Carts • Must carry the following drugs to treat and manage a crisis • 36 vials of the only known effective drug, dantrolene • Sterile water for dilution of dantrolene • Sodium bicarbonate (8.4%) 50mL x 5 • Calcium chloride (10%) 10 mL vial x 2 • Regular insulin 100 units/mL (refrigerated) • Lidocaine for injection (2%) 100 mg/5 ml or 100 mg/10 ml in preloaded syringe x • Refrigerated cold saline solution (at least 3000mL for cooling)

  11. MH Carts • Must carry the following equipment • Syringes 60 mL x 5 • IV catheters: 16G, 18G, 20G, 2-inch; 22G, 1-inch; 24G, 3/4-inch (4 each) (for IV access and arterial line) • NG tubes • Toomy irrigation syringes • Temperature probes • CVP kits • Transducer kits for arterial and venous cannulation • Large sterile drape • Urine meter • Irrigation tray with piston syringe • Large clear plastic bags for ice

  12. MH Carts • Equipment (cont.) • Small plastic bags for ice x 4 • Bucket for ice • Test strips for urine analysis • Laboratory Testing Supplies • Syringes for blood gas analysis • Blood specimen tubes for laboratory analysis • Urine collection container for myoglobin • MH carts must be accessible no more than 10 minutes after a crisis is identified • 5 is recommended

  13. Dantrolene • Brand names Dantrium, Dantamacrin, or Dantrolen • Dantrolene is currently the only available drug for the treatment of MH • Mortality of MH decreased from 80% to <10% with its introduction in the 1960s • Dantrolene’s mechanism of correcting MH is not fully understood (Krause, T., Gerbershagen, M. U., Fiege, M., Weißhorn, R., & Wappler, F., 2004)

  14. Dantrolene • In a retrospective study performed by Brandom, BW, and Larach, MG, 164 MH patients treated with dantrolene, muscle weakness was observed in 22% of patients, phlebitis it 10%, respiratory failure in 3%, and GI discomfort in 3% • When used with verapamil, dantrolene has been associated with a significant decrease in cardiac function in animal models • This interaction has not been observed in humans but using both drugs at the same time should be avoided (Krause, T., Gerbershagen, M. U., Fiege, M., Weißhorn, R., & Wappler, F., 2004)

  15. Dantrolene • In MH susceptible patients, dantrolene prophylaxis prior to anesthesia has not been shown to be significantly effective • The side effects of the drug do not outweigh the potential benefits of dantrolene prophylaxis (Krause, T., Gerbershagen, M. U., Fiege, M., Weißhorn, R., & Wappler, F. , 2004)

  16. Treatment • There are specific guidelines for treatment of an acute MH crisis • These are the guidelines according to Rosenberg, Davis, James, Pollock, and Stowell (2007) • Stop potent inhalation agents and succinylcholine • Increase minute ventilation to lower end-tidal CO2 • Get help • Prepare and administer dantrolene • 2.5mg/kg bolus • Titrate dantrolene to tachycardia and hypercarbia • 10mg/kg suggested upper limit but more may be given as needed • Begin cooling measures • Use iced solutions (ice packs to groin, axilla, neck) • NG lavage with iced solution • Stop cooling measures at 38.5⁰C to prevent accidental hypothermia

  17. Treatment (cont.) • (cont.) • Treat arrhythmias as needed; do not use calcium blockers • Secure blood gases, electrolytes, creatine kinase, blood and urine myoglobin • Coagulation profile check every 6-12 hours • Treat hyperkalemia with hyperventilation, glucose, and insulin • Once crisis is under control, contact MH hotline • Continue dantrolene at 1mg/kg every 4-8 hours for 24-48 hours • Ensure urine out put of 2 ml/kg/hour with mannitol, furosemide, and fluids as needed • Evaluate need for invasive monitoring and continued mechanical ventilation

  18. Treatment (cont.) • (cont.) • Observe patient in Intensive Care Unit for at least 36 hours • Refer patient and family to MH Testing Center for contracture or DNA testing • Patients should receive treatment and monitoring for 48-72 hours • 25% of patients with experience a recurrence of the condition

  19. Resources • Healthcare Professional MH 24-Hour Hotline • United States 1-800-644-9737 • Outside US 00-1-209-417-3722 • MHAUS Crisis Resources • Mixing Dantrolene Sodium For Injection Video • Printable Emergency Therapy for MH • MH App for iPhone (MHAUS, 2014)

  20. References Krause, T., Gerbershagen, M. U., Fiege, M., Weißhorn, R., & Wappler, F. (2004 March 16). Dantrolene – A review of its pharmacology, therapeutic use and new developments. Anesthesia, 59, 364-373. doi:10.1111/j.1365-2044.2004.03658.x Malignant Hyperthermia Association of the United States. (2014). How to Be Prepared. Retrieved from http://www.mhaus.org/healthcare-professionals/be-prepared Malignant Hyperthermia Association of the United States. (2014). Managing An MH Crisis. Retrieved from http://www.mhaus.org/healthcare-professionals/managing-a-crisis Rosenberg, H., Davis, M. James, D., Pollock, N., & Stowell, K. (2007 April 24). Malignant hyperthermia. Orphanet Journal of Rare Diseases, doi: 10.1186/1750-1172-2-21 Yang, T., Ta, A. T., Pessah, I. N., & Allen, P. A.. (2003 May 5). Functional Defects in Six Ryanodine Receptor Isoform-1 (RyR1) Mutations Associated with Malignant Hyperthermia and Their Impact on Skeletal Excitation-Contraction Coupling. The Journal of Biological Chemistry.doi: 10.1074/jbc.M302165200

  21. Images Used PACKAGE LABEL.PRINCIPLE DISPLAY PANEL-250ML. (n. d.) Isoflurane. Revised: 11/2013.Retrieved from http://www.drugs.com/pro/isoflurane.html RL-0186. (n. d.) Quelicin™ SUCCINYLCHOLINE CHLORIDE INJECTION, USP.Revised: 07/2011. Retrieved from http://www.drugs.com/pro/quelicin.html 1 in 5 Spinal Cord Surgery Patients Develop PTSD. (n. d.) PTSDPerspectives.Retrieved from http://ptsdperspectives.org/1-in-5- spinal-cord-surgery-patients-develops-ptsd/ Malignant Hyperthermia Cart. (n. d.) MPD Medical Systems.Retrieved from http://mpdmedical.com/products/hyper/malignant- hyperthermia-cart/163 Dantrium IV. (n. d.) JHP Pharma.Retrieved from http://www.jhppharma.com/products/brands/product-dantriumiv.php What is MH? MHAUS Home Page. (n. d.) Malignant Hyperthermia Association of the United States.Retrieved from http://www.mhaus.org/ Anesthesia. (n. d.) CHAlleNGE. See Change within Challenge. Retrieved from http://www.challengedoctor.com/anesthesia Revello, S. (11 December 2012). Malignant Hyperthermia: Malignant Hyperthermia Dantrolene’s role in the therapy. Retrieved from http://flipper.diff.org/app/items/info/5018 Mitchell, M. (1978). Treatment: Hyperthermia. National Cancer Institute. Retrieved from: http://commons.wikimedia.org/wiki/File:Nci-vol-1953-300_hyperthermia_patient.jpg

  22. Reflective Letter I made this Powerpoint because malignant hyperthermia is a rare condition that is deadly due to its unpredictable nature. I made this document filled with information about the condition because my audience is nurses and doctors. These professionals lead busy lives, so they need their information to be concise yet clear. I tried to avoid unnecessary information and transitions to allow myself to focus on only the important information. When healthcare professionals are in a lecture about a specific condition, they only focus on the relevant information that will help them in making a diagnosis and creating a treatment plan. This powerpoint is ideal for a hospital worker because it offers only the information that they need and nothing else to slow them down. I think that my audience would encounter this document in a lecture setting. Since it is a Powerpoint, it can be emailed but I believe that making providers take an hour out of their day to absorb the information is the best way to relay this material. This material is very important in a surgical setting, so providers need to be completely focused on it.

  23. Note I think that this piece fits in well to my professional portfolio. It is an informative yet concise source of educational material about a very important topic in all types of surgery. I have presented this information in a way that may not be very interesting to read, but it is definitely an effective way to get the relevant information into the provider’s hands.