malignant hyperthermia [final]

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Malignant HyperthermiaPresenter: Sumit GuptaModerator: Dr. Anjolie Chhabra Additional Prof. AnesthesiologyAIIMS, New Delhi

IntroductionMalignant HyperthermiaPharmaco-genetic disorderIn Genetically Susceptible.On exposureVolatile inhalational agents & Sch.Abnormal intracellular CaRapid Body Temperature: HyperthermiaSkeletal muscle activity Rhabdomyolysis and metabolic acidosis Death

Malignant

HISTORYIst case reported ~ 1960: Australia Danbourough And Lovell21 year/M malleolar # fixationGeorge Locher (Wisconsin) and Beverly Britt (Toronto)Familial disorderCentral loss of temperature control Disorder of skeletal muscle metabolism1966: Wilson et alIst coined the term malignant hyperthermia2001: Punj et al (IRCH): Ist case of MH in India

History of 10 anesthesia related deaths in the family

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PATHOPHYSIOLOGYNORMAL PHYSIOLOGYSTORE OPERATED CALCIUM ENTRY

1.Motor neuron releases Ach2.Ach binds to Ach receptors -opens Na channels & generates APs3. AP reaches T tubule4. Voltage Sensor DHPR receptors activated 5.Ca is released from SER via Ryanodine receptor. (3isoforms: Cardiac, Skeletal, Brain). Biphasic response to Ca & Inhibited by Mg

6. Ca binds to Troponin and promotes actin-myosin interaction7. SERCA pumps propel Ca back to the SR & cause relaxation when Ca is 90%Detects abnormal muscle response to Halothane and caffeine.RequiresMuscle Harvesting: Quadriceps(MC),Rectus abdominus. Specimen Length: 15-25 mm, Thickness: 2-3 mm and Weight 100-150 mg (max 2-4gm).Local infiltration or femoral and lat. Femoral cut. nerve block.Weight>30 Kg and age > 4 years

It is 99 % sensitive and specific. BUTInter laboratory variability.Averages are recordedAccuracy of caffeine and halothane concentrations.

CONTRACTURE TESTIndicationsHistory of hyperthermic reaction under GANegative Genetic analysis in a suspected caseRecurrent RhabdomyolysisRecord Contracture Caffeine > 2mmol/l and halothane >2%(IVCT)/3% (CHCT)Localized contracture testMicrodialysis based Infusion of caffiene or halothane into muscle Acid base changes in muscle

+ve test: Contracture > 0.2 GCaffeine conc.2%.MH SusceptiblePositive response to both halothane and caffeineMHc: Positive response to Caffeine MHH:Positive response to halothane.

MH Normal Contracture less than 2 g at Caffeine >3mmol/L or Halothane>2%.

NON ANESTHETIC MHAnimal model of Human MHAR : InbreedingHomozygous for RyRMH like syndrome with stressors:Endogenous & exogenous stressor

Assoc. with Recurrent Exertional Heat stroke alsoAll MH suspectibleKing Denbourough syndrome.Abn facies with prox. MyopathyCentral Core diseaseCPK may be normal.+ve IVCTEvans myopathy

Awake MHMH in the absence of classical triggersCoexistent 2nd mutation Higher susceptibility to exogenous triggerExtreme Physical activity in hot surroundingsInfectious fever

NON ANESTHETIC MH

NOT AUTOSOMAL DOMINANTHeat,Oxidative stress Non invasive : P31 MRIAt Risk of MHHypertrophyMuscle HypotoniaSpasmOpthalmoplegia .

COMING BACK TO ELEPHANT IN THE ROOM

MH: Clinical presentation INCIDNCEWORLD : 1: 10,000 1:220,000.JAPAN : 1:60,000 1:73,000.INDIA: Under reported 16- 17 cases

Mortality:Intially: 70%.With Dantrolene: 1.4-5%

Clinical PresentationsMales> femalesMC in young age, muscularENT/DENTAL/SQUINT Most Rapid onset halothane + SchMH can occurPreviously Uneventful anesthesia exposure MAC requirement is highest in young age

Exposed to higher dose.

Fulminant MHImmediate onsetRapid Course

Insidious MHDelayed Onset.Can present even in Recovery Room

TYPES

Redo clinical presentation19

PATHOGENESIS

CLINICAL FEATURES

1. HYPERCARBIA IS ALSO EARLIEST SIGN OF MH2. MASSTER SPASM CAN EVEN PRECEDE HYPERCARBIA BUT PRESENT ONLY IN 27%.

CLINICAL FEATURESEARLY SIGNS

Inappropriately elevated CO2 production (EtCO2, RR). O2 ConsumptionMixed Metabolic and Respiratory acidosisProfuse Sweating.Mottling of skin.1.Inappropriate tachycardia2.Cardiac arrhythmias (Ventricular ectopics &Bigemini).3.Unstabele arterial Pressure.1.Masster Spasm with Sch.2. Generalized Muscle rigidity METABOLICCARDIOVASCULARMUSCLETEMPERATURE CAHANGES ARE LATE SIGNS

CLINICAL FEATURES

Rapid rise in Core body temperature. Severe Cardiac arrhythmias.Cardiac arrest.

PHYSICAL

HyperKalemia.Grossly elevated CPK.Grossly elevated Blood Myoglobin.Dark Colored urine5. D.I.C.

LABORATORY

Rapid rise in Temperature and high Temperature correlate with Mortality .Core Temperature monitoring shows mortality benefit as time to administer Dantrolene is shortened. No benefit of skin Temperature monitoring.

Clinical ScoreLarach Score (1994)

Clinical ScoreLarach Score (1994)

Differential diagnosis for a GREAT MIMICAnaphylactic reactionDiabetic comaDrug toxicity or abuseEquipment malfunction with increased carbon dioxide (CO2)Exercise hyperthermiaHyperthyroidismHypoventilation or low fresh gas flowIncreased ETCO2 from laparoscopicsurgeryInsufficient anesthesia or analgesia (or both)Intracranial free bloodMalignant neuroleptic syndromeMuscular (Duchenne and Becker) dystrophies/MyotoniasPheochromocytomaRhabdomyolysisSepsis

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TREATMENT

IMMEDIATELYDeclare emergency and call for Help.Inform surgeons Termination of SurgeryStop all Inhalational agentsSwitch to Non Trigger anesthesiaHyperventilation with flow 10 L 100% O2Disconnect circuit.Inform1800-MHHYPERMonitoringECG, NIBP, EtCO2Wide bore IVConsider CVP, Arterial early InvestigationK+, CPK, ABG, Myoglobin, Blood sugar

TREATMENTDantroleneHydantoin derivative2.5 mg/kg Max 10 mg/Kg20 mg/ ampoule 16-20 ampoulesMixed with sterile water.NaOH(pH-9-10), Mannitol (isotonic)Others solun. precipitation.t1/2: 10 -15 hoursS/E: Respiratory muscle weakness, Cholestasis

TREATMENT

Observe for at least 24 hours in ICU.

Recrudescence risk is 50%

AAGBI TEMPLATE MH

AAGBI SAMPLE MH KIT

COMPARTMENT 1Dantrolene100 ml sterile water X 12 Dantrolene X12 vials.50 ml syringe X 10Location of Dantrolene

COMPARTMENT 2Treatment Amiodarone 300 mg BlockersCalcium chloride/luconateSoda bicarb 50mlPropofol vialsGlucose 20%

COMPARTMENT 3InvestigationsBlood vials: Biochem., FBC, Coagulation, Urine Sample, GroupingArt & CVP Canula & Transducer

COMPARTMENT 4Fridge pack2l NaCl 4 degree CInsulin

COMPARTMENT 3InvestigationsBlood vials: Biochem., FBC, Coagulation, Urine Sample, GroupingArt & CVP Canula & Transducer

Masseter SpasmUsually seen after SchJaw muscle Rigidity with whole body flaccidity > 2min. MH susceptibility: 30%.Higher risk Jaw + whole Body rigidityJaws of steelMost severe variantVentilation and Intubation might not be possible.Stop surgerySurgeryControversial in othersTo proceed or to stop

Slow Tonic fibers in Jaw muscleGradingGrade 1: Jaw stiffness onlyGrade 2: Jaw stiffness interfering with intubationGrade 3: Jaws of Steel

Drugs causing MHSchVolatile agentsHAL>ISO>ENF>SEVO.ONDANSETRON

ANESTHESIA MH SUSCEPTIBLITYAvoid trigger agentsFlush the circuit with 10 L O2.Use Charcoal filter in anesthesia machineTIVARegional anesthesia.Xenon (Case Report)

Thank you

HISTORY1915-19253 deaths in a family after Anesthesia. Retrospective sis : Muscle biopsy on descendants.OmberdanneDescribed syndrome of hyperthermia and muscle rigidity.1966: Wilson et alIst coined the term malignant hyperthermia.

HISTORY1966Hall et alMalignant hyperthermia in pigsOn exposure to halothane and Succinyl Choline.1975:Harrison et alIst use of Dantrolene in MH.2001:J. Punj et al:Ist case of MH in India.

HISTORY

Ist successful survival in case of malignant hyperthermiaProves that Subarachnoid block can be used safely

HISTORY

Highlighted the non Availability of Dantrolene in India

PATHOPHYSIOLOGY SERCA pumpsPropel Ca back to the SRRelaxation Ca is