malignant hyperthermia. history history pathophysiology pathophysiology diagnosis diagnosis signs...

Malignant HyperthermiaMalignant Hyperthermia


• HistoryHistory

• PathophysiologyPathophysiology

• DiagnosisDiagnosis

• Signs and SymptomsSigns and Symptoms

• TreatmentTreatment


• HistoryHistory– Initially identified in Australia 1961Initially identified in Australia 1961– Initially very high mortalityInitially very high mortality– Diagnostic testing 1971Diagnostic testing 1971– Association with Masseter muscle Association with Masseter muscle

rigidity 1970rigidity 1970– Dantrolene 1975Dantrolene 1975– Genetic component identified 1990”sGenetic component identified 1990”s– DNA testing ?DNA testing ?


• Caused by mutation of the sarcolamma ryanodine Caused by mutation of the sarcolamma ryanodine receptor RyR1 which is coded on chromosome 19 receptor RyR1 which is coded on chromosome 19

• Responsible for intracellular calcium metabolismResponsible for intracellular calcium metabolism

• RyR1 receptorRyR1 receptor


• IncidenceIncidence• 1/200000 ---- 1/200000 ---- with Succinylcholine 1/65000with Succinylcholine 1/65000• Mortality with treatment 10 %Mortality with treatment 10 %

– Poor outcome related to delay in administering Poor outcome related to delay in administering Dantrolene and peak temperatureDantrolene and peak temperature


• TriggersTriggers– SuccinylcholineSuccinylcholine– Volatile “….ane” anaestheticsVolatile “….ane” anaesthetics– Not N2ONot N2O– All other anaesthetic drugs safe All other anaesthetic drugs safe

Malignant HyperthermiaMalignant Hyperthermia1. MH occurs because of an increase in metabolism due to

rapid and uncontrolled increase in calcium within the sarcolema (muscle cells).

http://www.google.com/url?sa=i&rct=j&q=muscle%20cell%20in%20malignant%20hyperthermia&source=images&cd=&docid=QhGURgotf-WinM&tbnid=IEPwb6RtvVjIGM:&ved=0CAUQjRw&url=http%3A%2F%2Fflipper.diff.org%2Fapp%2Fitems%2Finfo%2F5018&ei=gYrqUbelEMzEPKDFgZgF&bvm=bv.49478099,d.bGE&psig=AFQjCNFoZMMXhnv0fwZ6PBT8aOOElrng_g&ust=1374411774340240


2. 2. The increase in calcium level overwhelms the capacity of the muscle cell for active calcium reuptake.

33. 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.


• Familial Dominant trait but with incomplete Familial Dominant trait but with incomplete penetrancepenetrance

• Males more common than femalesMales more common than females

• May May not not trigger with first exposure to volatilestrigger with first exposure to volatiles

• Succinylcholine greatly increases riskSuccinylcholine greatly increases risk

Diseases Associated with MHDiseases 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


• Early SignsEarly 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 ?


• Late SignsLate SignsTachypneaArterial hypoxemiaMetabolic / Respiratory acidosisHyperkalemiaCardiac arrhythmias HypotensionHyperthermiaRhabdomyolysis Increased CPK –20,000 I.U

Malignant HyperthermiaMalignant Hyperthermia Differential DiagnosisDifferential 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 HyperthermiaMalignant HyperthermiaTreatmentTreatment

• 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


• 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


• 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 HyperthermiaMalignant HyperthermiaKKey Patient Stability Indicatorsey Patient Stability Indicators

• ETCOETCO22 is declining or normal is declining or normal

• HR is stable or decreasingHR is stable or decreasing

• No ominous dysrhythmiasNo ominous dysrhythmias

• Temperature is decliningTemperature is declining

• Generalized muscular rigidity is resolving Generalized muscular rigidity is resolving (if present)(if present)

• IV dantrolene administration has begunIV dantrolene administration has begun

Malignant HyperthermiaMalignant HyperthermiaWhat is Dantrolene ?What is Dantrolene ?

• Dantium ( Dantrolene )Dantium ( Dantrolene )– Skeletal muscle relaxant by inhibiting Skeletal muscle relaxant by inhibiting

sarcoplasmic release of calciumsarcoplasmic release of calcium– Half life 4-8 hrs metabolized by liverHalf life 4-8 hrs metabolized by liver– Causes generalized muscle weaknesCauses generalized muscle weaknes– No cardiac effectsNo cardiac effects– No effect on train of fourNo effect on train of four

Management of MH Management of MH Susceptible PatientsSusceptible Patients

• Preparation of anaesthesia machinePreparation of anaesthesia machine– Fresh circuit, absorber flushed at 10 lpm x 10 minFresh circuit, absorber flushed at 10 lpm x 10 min– Triggers disconnected from circuit and out of Triggers disconnected from circuit and out of

roomroom

• Non triggering anaestheticNon triggering anaesthetic– Propofol, ketamine, N2O,narcoticsPropofol, ketamine, N2O,narcotics– Regional techniquesRegional techniques

• PACUPACU– Extended stayExtended stay– Observe 2-4 hours prior to dischargeObserve 2-4 hours prior to discharge

For More MH InformationFor More MH Information

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