Malignant Hyperthermia Barbara Robertson MD FRCPC Dept of

Malignant Hyperthermia Barbara Robertson, MD, FRCPC Dept of Anesthesia, PAH

Overview • • • What is it? Why is it? Who gets it? How do you recognize it? How do you treat it? What to do if patient is susceptible?

1960 First case described 1962 Inherited component suggested 1960’s Toronto and Wisconsin MH families identified / similarity to PSS recognized 1971 International symposium Toronto 1971 CHCT muscle biopsy described 1975 Dantrolene found to be specific treatment (FDA approved 1979) 1981 -82 Patient advocacy groups formed 1980’s Use of intraoperative capnography helps early detection 1990’s RYR 1 gene mutation discovered (100% PSS, 50% MH) 2000’s Genetic testing available

Resources at hand • • • MH hotline: 1 -800 -644 -9737 Outside USA: +1 -303 -389 -1647 Website: www. mhaus. org Wall flow chart from MHAUS There’s an app for that (e. Pocrates, Gas Guide, MHapp)

What is MH? • Potentially fatal inherited disease • Fever, rigidity, acidosis • Hypermetabolic state of skeletal muscles with high intracellular calcium levels • Triggered by exposure to volatile anesthetics and / or succinylcholine

Why is it? • It’s complicated! • Uncontrolled release of calcium by the ryanodine receptor in the terminal cisternae of the sarcoplasmic reticulum

Intracellular hypercalcemia • • Increased calcium release Decreased calcium uptake Defect in the muscle membrane Altered function / structure of proteins & fatty acids

Trigger agents • Volatile anesthetic gases (sevo, des, etc) • Succinylcholine

Safe drugs in MH • N 20 • Nondepolarizing relaxants (roc, vec, atracurium etc) • Local anesthetics • Narcotics • Sedative hypnotics (midaz, propofol etc)

Who gets it? • 1: 50, 000 adult GAs • 1: 15, 000 pediatric GAs • Incidence rising due to better awareness but mortality declining (overall 10%) • Inherited as autosomal dominant with variable penetrance

Conditions associated with MH • Central core disease • Myotonia flutuans • King or King-Denborough myopathy • Osteogenesis imperfecta • Heat / exercise syndromes?

Other conditions • Muscular dystrophy (hyperkalemia after sux but not MH) • Pheochromocytoma & thyrotoxicosis show hypermetabolism but not MH • Neuroleptic malignant syndrome (related to phenothiazine exposure over long term causing dopamine depletion)

How to recognize it? • • Classically presents in OR Tachycardia Tachypnea Hypertension Arrhythmias Rigidity Hyperthermia

As the crisis develops…. • • • Rising ET CO 2 absorbent gets hot Skin colour mottled or cyanotic Sweating Mixed respiratory & metabolic acidosis • Elevated K, lactate, myoglobin, CK

Later…. . • Myoglobinuric renal failure • DIC • Death

Variable presentations • Delay in onset until emergence, PAR or ward • Masseter muscle rigidity • Several uneventful GA’s in the past, then MH occurs during current GA

Diagnostic tests • Caffeine halothane contracture test is the gold standard (muscle biopsy) • 5 centres in North America perform the accepted protocol (Toronto is only one in Canada listed on MHAUS website) • Genetic testing (2 centres in USA listed on MHAUS website)

Problems with testing • False negative (had MH after testing negative) • More than one gene mutation may cause MH because only 50% to 80% of MH susceptible patients have RYR 1 variant or mutation

How to treat? • Early diagnosis and treatment result in very low mortality • Any location where anesthetics are administered should have MH plan & sufficient dantrolene • MH cart, practice drills, wall chart with hotline number

MH treatment memory aid • • Some Hot Dude Better Give Iced Fluids Fast

Acute phase • Call for help & get the MH cart / crash cart • Declare an emergency • Stop the triggering agents • Hyperventilate with high flow 100% O 2 • Switch to non triggering anesthesia to finish the surgery if needed / change circuit? • Dantrolene

Dantrolene • Need help to mix • Initial dose 2. 5 mg/kg (175 mg) • Each bottle is 20 mg = 9 bottles for first dose • Each bottle mixed with 60 ml H 2 O = 540 ml water for 9 bottles • Acts by reducing intracellular calcium in skeletal muscles

Acute Episode (cont’d) • Cool patient (goal = 38) • ABG, lytes results guide further treatment for metab & resp acidosis, hyperkalemia • Arrhythmias respond to correction of hypercapnia, hyperkalemia & acidosis • CK level, myoglobin

Afterwards, monitor for…. • Recrudescence (25% of patients) • DIC • Myoglobinuric renal failure

In ICU: • Dantrolene 1 mg/kg q 6 hr x 24 -36 hours then orally? • EKG, art line, urinary catheter, temperature, 2 nd IV line • CVC? , capnography? • Monitor & treatment for specific abnormalities

ICU care (cont’d) • Refer patient & family to MH centre for testing • Recommend registry in MHAUS data base • Recommend Medic Alert bracelet

ABC’s • A: • Aware of recrudescence • Ask relatives anesthesia / neuromusc disease history • B: • Biopsy • C: • Contact MHAUS

ABC’s + D • D: • Dantrolene 1 mg/kg IV q 6 h x 24 36 hrs • Documentation to MHAUS registry

Management of MH susceptible patient • Refer to anesthesia consult clinic • Prophylaxis with dantrolene? • Hospital setting vs private clinic? • GA vs local / regional?

GA in MH susceptible • Flush gas machine / remove vaporizers / new circuit & CO 2 absorber • Monitor ETCO 2 & temp • MH cart ready & nearby • TIVA with propofol +/- N 2 O +/nondepolarizing NMB + narcotics = non trigger anesthesia • Use high fresh gas flow

MH cart • Dantrolene • Sterile water (in warming cupboard? ) • Bicarb, dextrose, Ca. Cl 2, lidocaine • Insulin (in fridge) • NS IV bags (in fridge) • Other stuff

PAR care for MH susceptible • Observe for 4 – 6 hours • May be appropriate for day surgery if GA was uneventful

Thank you!