What is Malignant Hyperthermia, Diagnosis and Prevention.

Malignant Hyperthermia (MH) is a clinical condition and disorder of muscle metabolism triggered by succinylcholine and volatile anesthetic agents, which leads to a life-threatening state of hypermetabolism. Volatile anesthetics and succinylcholine are the primary triggers of MH, while other medications can also cause hypermetabolism and cause MH. The leading cause of MH is mutations in the ryanodine receptor. In susceptible individuals, the abnormal ryanodine receptor in the muscle interferes with the muscle’s calcium regulation. The abnormal ryanodine receptor that controls the release of calcium causes the skeletal muscle to accumulate calcium. This hypermetabolism leads to increased dioxide, metabolic and respiratory acidosis development, rapid absorption of oxygen, thermal generation, nervous system sympathetic activation, intravascular dissemination hyperkalemia, and multiple organ dysfunction and insufficiency. A rise in carbon end-tidal dioxide (even with improved minute ventilation), tachycardia, muscle rigidity, tachypnea, and hyperkalemia is early clinical symptoms of MH. Subsequent symptoms include fever, myoglobinuria, and failure of several organs. Malignant Hyperthermia is more common in men than women. MH is less frequent in adults older than 50 years and in infants.

Diagnosis

Early signs of malignant Hyperthermia include

• End-tidal CO2 rise
• In the ventilated patient, over-breathing or rise in minute ventilation to retain end-tidal CO₂
• Tachycardia
• Tachypnea in unventilated patient

Late signs of malignant Hyperthermia include

• Fever
• Metabolic acidosis
• Coagulopathy, Disseminated Intravascular Coagulation (DCI),

Other signs

• The rigidity of skeletal muscles
• High serum Creatine Kinase
• Myoglobin in urine and serum
• Elevated serum potassium (K+), Calcium (Ca++), and lactate
• Irregular heart rate
• Instability of hemodynamic status

Prevention

Before surgery, patients suspected of MH susceptibility should be checked. It comprises muscle biopsy, contracture monitoring, and serum creatine kinase (CK) level. If this cannot be done (e.g., an emergency operation), prevent triggers.

• Uninstall system vaporizers.
• Substitute a fresh absorbent for an absorber of CO2.
• Flush Machine with air or high-flow oxygen for at least 10 minutes
• Make MH treatment cart available.
• Avoid volatile anesthetics, succinylcholine that can trigger MH.
• Monitor the patient closely during and after surgery for any signs of MH. Consider a 3–5-hours stay in PACU before discharge.

Treatment

• Confirm diagnosis or, when in doubt, provide treatment for MH.
• Stop administration of volatile anesthetic agent and succinylcholine.
• Provide 100% oxygen with >10 L/minute of high flow with anesthesia circuit for hyperventilation.
• Administer 2.5 mg/kg dantrolene IV as soon as possible. Dilute 20mg vial of dantrolene 60cc of sterile water. If physiologic or metabolic abnormalities of MH present, then repeat the dose of dantrolene every 5 – 10 minutes (do not exceed 10mg/kg). After surgery and MH crisis, administer 1 mg/kg of dantrolene every 6 hours for 24 – 48 hours.
• Stop or finish the surgery as soon as possible.
• Monitor and correct metabolic and physiologic abnormalities; Arterial blood gases, serum electrolytes, and blood coagulation status.
• Sodium bicarbonate is administered for Metabolic acidosis, as guided by ABG analysis. Empirically give 1–2 mEq/kg IV in the absence of ABG.
• Hyperkalemia treatment requires calcium, sodium bicarbonate, hyperventilation, glucose, and insulin.
• Cardiac arrhythmia’s typically respond to the treatment used for acidosis. Administer standard antiarrhythmic drugs if necessary, avoid calcium channel blockers.
• Urine output should be maintained at least 1–2 mg/kg/h.
• Place urinary catheter.
• Give IV normal saline.
• When appropriate, administer 10-20 mg IV furosemide or 0.5-1 g/kg mannitol for diuresis if necessary.
• Cool if Hyperthermia is present; provide the patient with cooling. Take into account the following options and monitor the temperature to prevent hypothermia.
• Surface cooling blanket
• Gastric lavage
• Irrigation of wounds (e.g., open peritoneal cavity)
• Post-care arrangement in ICU.

Summary:

The total occurrence of malignant hyperthermia is estimated to be 1 in 50,000 adults given anesthetics and 1 in 15,000 children given anesthetics. While the frequency of confirmed cases of MH has increased, the mortality rate from MH has decreased by about 10%, suggesting both a high understanding of the syndrome and earlier diagnosis, followed by improved care.

References

1. Suyama, H., Kawamoto, M., & Yuge, O. (2002). Prevention and treatment of malignant hyperthermia in certified training hospitals in Japan: a questionnaire. Journal of Anesthesia, 16(3), 207–210. doi:10.1007/s005400200026 
2. Hopkins PM. Malignant hyperthermia: pharmacology of triggering. Br J Anesthesia. 2011 Jul;107(1):48-56. doi: 10.1093/bja/aer132. Epub 2011 May 30. PMID: 21624965.
3. Pardo, M., & Sonner, J. M. (n.d.). Manual of Anesthesia Practice. Cambridge university press.
4. Pollard, B. J., & Kitchen, G. (n.d.). Handbook of Clinical (4th ed.). CRC Press.
5. Glahn KP, Ellis FR, Halsall PJ, Müller CR, Snoeck MM, Urwyler A, Wappler F; European Malignant Hyperthermia Group. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010 Oct;105(4):417-20. doi: 10.1093/bja/aeq243. PMID: 20837722.
6. Rosenberg, H., Pollock, N., Schiemann, A., Bulger, T., & Stowell, K. (2015). Malignant hyperthermia: a review. Orphanet journal of rare diseases, 10, 93. https://doi.org/10.1186/s13023-015-0310-1
7. Hopkins PM, Malignant hyperthermia: pharmacology of triggering, BJA: British Journal of Anesthesia, Volume 107, Issue 1, July 2011, Pages 48–56, https://doi.org/10.1093/bja/aer132
8. AAGBI. (2015). Malignant Hyperthermia Crisis, AAGBI Safety Guideline. http://www.aagbi.org /sites/default/files/MH%20laminate.pdf