Malignant Hyperthermia

Barbara Robertson, MD, FRCPCDept 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 RYR1 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 (ePocrates,

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

• N20• 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 CO2• CO2 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% O2• 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 H2O =

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 1mg/kg q6hr x 24-36 hours then orally?

• EKG, art line, urinary catheter, temperature, 2nd 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 q6h 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 & CO2 absorber

• Monitor ETCO2 & temp• MH cart ready & nearby• TIVA with propofol +/- N2O +/-

nondepolarizing NMB + narcotics = non trigger anesthesia

• Use high fresh gas flow

MH cart

• Dantrolene• Sterile water (in warming

cupboard?)• Bicarb, dextrose, CaCl2, 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!Thank you!