Malignant Hyperthermia Study Guide.docx

**Malignant Hyperthermia** Triggering Agents - Succinylcholine (Anectine) - Sevoflurane (Ultane) - Desflurane (Suprane) - Isoflurane (Forane) - Enflurane (Ethrane) - Halothane (Fluothane) Pathophysiology - Malignant hyperthermia is often linked to mutations in the **RYR1**...

**Malignant Hyperthermia** Triggering Agents - Succinylcholine (Anectine) - Sevoflurane (Ultane) - Desflurane (Suprane) - Isoflurane (Forane) - Enflurane (Ethrane) - Halothane (Fluothane) Pathophysiology - Malignant hyperthermia is often linked to mutations in the **RYR1** gene, which encodes the ryanodine receptor in skeletal muscle. This receptor regulates calcium release from the sarcoplasmic reticulum (SR) into the cytoplasm. - In individuals with MH, the defective ryanodine receptor becomes overly sensitive to triggering agents. - Exposure to triggering agents causes excessive calcium release from the sarcoplasmic reticulum into the cytoplasm of muscle cells. Normally, calcium is released to initiate muscle contraction, but it is tightly regulated to allow controlled contraction and relaxation. - In MH, this uncontrolled release leads to sustained muscle contraction and a hypermetabolic state. - The increase in cytoplasmic calcium stimulates continuous ATP consumption as muscles contract and try to pump the calcium back into the sarcoplasmic reticulum. - This leads to a significant increase in oxygen consumption, CO2 production, heat generation, and lactic acid buildup. - The body's attempt to deal with this crisis results in acidosis, hyperkalemia (elevated potassium levels), hyperthermia (rapid rise in body temperature), and rhabdomyolysis (breakdown of muscle tissue) - Associated with **Central Core Disease** and **King Denborough Syndrome** Incidence - 1 in 20,000 -- 50,000 - Susceptible patients may not go into MH with every triggering agent administration (may have had previous anesthetic with triggering agent with no complications) Onset - Can be immediately following admin of triggering agent - Can also occur delayed in PACU - Environmental factors (overheating, excessive physical exertion) can trigger syndrome in some patients. Symptoms -- Key Clinical Signs - Muscle rigidity may or may not be present - Masseter Muscle Rigidity - Temperature is a late sign - **Increased End-tidal CO~2~** is an early sign - **Hot/Exhausted CO~2~ absorbent** - **Tachycardia** almost always present w/ wo HTN - Recrudescence despite treatment - **Tachypnea / increased MV** Other Clinical Indicators, Later Signs - Ventricular Dysrhythmias - Skin Mottling - Myoglobinuria - DIC Laboratory Findings - Respiratory acidosis - Increase a-v pCO2 gradient - Metabolic (lactic) acidosis - Hyperkalemia - HyperCKemia - Elevated Serum and urine Myoglobin - Abnormal coagulation tests - Hypercalcemia - Hypermagnesemia Immediate Treatment - Call for Help and notify OR team as soon as you suspect MH - Have someone call the MH hotline; MHAUS - Facility should have a designated cart/bag to treat and MH crisis; bring the code cart too - Vaper-Clean vent filters - Ryanodex/Dantrolene - Cold IV fluids - Bags of Ice - **Discontinue any triggering agent** - Hyperventilate with 100% O2 w/ high flows - Dantrolene/Ryanodex - Administer as soon as MH diagnosis is made - **Initial dose 2.5 mg/kg** - Each bottle contains 250mg of Ryanodex (dantrolene sodium) - Reconstitute w/ **5mL of STERILE WATER** - Admin rapidly thru large bore IV - Repeat doses as needed - *Dantrolene is a vesicant, use a central line or an IV in a large vein if possible.* Management - Lines - Largebore IV/ CVC - A-line - CVP - Foley - Lab testing - Serial Blood gases - Electrolytes, BUN, Creatinine Liver enzymes - CK, Myoglobinuria - DIC panel-PT, PTT, INR, fibrin split products - Core Temp Monitoring - Maintain urine output w/ fluids + diuretics Cooling Treatment - Turn down room temperature - Uncover patient - Ice packs to neck, groin, axilla - Cool IV fluids - Gastric lavage - Sterile ice in surgical field Dysrhythmias - Secondary to acidosis and hyperkalemia - Acidosis: NaHCO3 - Hyperkalemia: - Bicarbonate - Glucose/Insulin - **Calcium OKAY to use to treat hyperkalemia** - Avoid calcium channel blockers cardiac arrest After Immediate Treatment - Patient must go to the ICU - **Redose Dantrolene** **1 mg/kg q 4-6hrs** - Recurrence rate \~25% - Kidney protection with NS and sodium bicarb Testing for MH - **Caffeine Halothane Contracture Test -** Biopsy testing is still the gold standard -- 98-99% sensitive, 78-80% specific. If negative, then treat the patient and family as normal Differential Diagnoses - Light anesthesia - Inadequate ventilation - Rebreathing - Fresh gas flow - Thyroid storm - Infection/Sepsis - Pheochromocytoma - Iatrogenic overheating - Serotonin syndrome - Cocaine, ecstasy, amphetamine Other muscle disease (dystrophinopathy) - **Neuroleptic malignant syndrome closely resembles MH** - Myotonic syndromes - Cerebral ischemia - Ascending tonic-clonic syndrome - Rhabdomyolysis - Statins - Hypoperfusion - Exertional heat illness Preparation for Susceptible Patients - Shut down and/or disable vaporizers - Flow oxygen at 10 L/min for 20 minutes through machine and ventilator - Replace circuit and soda lime - New machines require longer flushing time - Check MH kit-have Ryanodex (dantrolene sodium) available - Dantrolene pretreatment not recommended - Use non-trigger agents or local anesthesia - Check with Manufacturer recommendations for anesthesia machine - Flush \> 60 minutes - Charcoal filters - Nitrous oxide - Barbiturates - Benzodiazepines - Intravenous induction agents - Propofol - Ketamine - Etomidate - Methohexital - Neuromuscular blocking agents (nondepolarizing) - Narcotic and opioid analgesia - Local anesthetic agents