Malignant Hyperthermia

Malignant Hyperthermia History Pathophysiology Diagnosis Signs and Symptoms Treatment

Malignant Hyperthermia History Initially identified in Australia 1961 Initially very high mortality Diagnostic testing 1971 Association with Masseter muscle rigidity 1970 Dantrolene 1975 Genetic component identified 1990”s DNA testing ?

Malignant Hyperthermia Caused by mutation of the sarcolamma ryanodine receptor RyR1 which is coded on chromosome 19 Responsible for intracellular calcium metabolism RyR1 receptor

Malignant Hyperthermia Incidence 1/200000 ---- with Succinylcholine 1/65000 Mortality with treatment 10 % Poor outcome related to delay in administering Dantrolene and peak temperature

Malignant Hyperthermia Triggers Succinylcholine Volatile “….ane” anaesthetics Not N2O All other anaesthetic drugs safe

Malignant Hyperthermia MH occurs because of an increase in metabolism due to rapid and uncontrolled increase in calcium within the sarcolema (muscle cells).

Malignant Hyperthermia 2. The increase in calcium level overwhelms the capacity of the muscle cell for active calcium reuptake. 3. This results in muscle contraction and increased breakdown of ATP, enhanced glycolysis, uncoupling of oxidative phosphorylation, & activation of actin-myosin filaments yielding significant heat production causing cell damage, and membrane leak.

Malignant Hyperthermia Familial Dominant trait but with incomplete penetrance Males more common than females May not trigger with first exposure to volatiles Succinylcholine greatly increases risk

Diseases Associated with MH King Denborough syndrome Caution in children with delayed motor function Ion channel mutations Myopathic syndromes Duchenne muscular dystrophy Brody’s Disease -deficient calcium, ATP (rhabdomyolysis, not MH) McArdles Diseas -glycogen storage (rhabdomyolysis, not MH) Myotonia congenita Central Core disease

Malignant Hyperthermia Early Signs Hypercarbia 40% - respiratory acidosis Innappropriate for case setting after considering opioids, ventilator settings, laparoscopic surgery etc If in doubt obtain blood gas Tachycardia 30% Masseter Spasm 20% Hypertension ?

Malignant Hyperthermia Late Signs Tachypnea Arterial hypoxemia Metabolic / Respiratory acidosis Hyperkalemia Cardiac arrhythmias Hypotension Hyperthermia Rhabdomyolysis Increased CPK –20,000 I.U

Malignant Hyperthermia Differential Diagnosis Neuroleptic Malignant Syndrome •Severe muscle rigidity and elevated temperature associated with the use of antipsychotic medication •Thyrotoxic crisis –Thyroid Storm •Cocaine toxicity •Heat stroke •Serotonin syndrome -excessive serotonin usually r/t combining meds •Status Epilepticus •Pheochromocytoma •Lymphoma

Malignant Hyperthermia

Malignant Hyperthermia Treatment Call for assistance Immediately terminate trigger drugs & conclude surgery as soon as possible •Hyperventilate with 100% oxygen •Initiate active cooling •Iced saline •Gastric lavage with iced saline Surface cooling

Malignant Hyperthermia Treatment Dantrium®IV-2 mg/kg IV q4-8hrs repeated 24-48hrs or until symptoms resolve ( max 10 mg/Kg ) Dantrium®IV each vial contains 1. 20 mg dantrolene sodium 2. 3000 mg mannitol 3. Sodium Hydroxide to yield a pH of approximately 9.5 when reconstituted with 60 mL sterile water

Malignant Hyperthermia Treatment Correct metabolic acidosis (NaHCO3 1-2mEq/kg IV based on arterial ph) Maintain urine output Hydration Furosemide ( 1mg/ kg ) Treat hyperkalemia – glucose + insulin Treatment of arrythmias Avoid Ca channel blockers – myocardial depression

Malignant Hyperthermia Key Patient Stability Indicators ETCO2 is declining or normal HR is stable or decreasing No ominous dysrhythmias Temperature is declining Generalized muscular rigidity is resolving (if present) IV dantrolene administration has begun

Malignant Hyperthermia What is Dantrolene ? Dantium ( Dantrolene ) Skeletal muscle relaxant by inhibiting sarcoplasmic release of calcium Half life 4-8 hrs metabolized by liver Causes generalized muscle weaknes No cardiac effects No effect on train of four

Management of MH Susceptible Patients Preparation of anaesthesia machine Fresh circuit, absorber flushed at 10 lpm x 10 min Triggers disconnected from circuit and out of room Non triggering anaesthetic Propofol, ketamine, N2O,narcotics Regional techniques PACU Extended stay Observe 2-4 hours prior to discharge

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