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Malignant Malignant Hyperthermia-Hyperthermia- The The

Heat is ONHeat is ON

Dr. Manish Singhal

KGH, Tralee,Ireland

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Anaesthetic Deaths in a Anaesthetic Deaths in a FamilyFamily

Denborough MA, Forster JFA, Lovell RRH, et al

Royal Melbourne Hospital

British J. Anaesth. 1962;34,395

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Some Landmarks in theSome Landmarks in theEvolution of Understanding Evolution of Understanding

MHMH

1960/611960/61 -- Denborough and Lovell describe Denborough and Lovell describe “Anesthetic deaths in a family” “Anesthetic deaths in a family”

1960s1960s -- Gordon (?) Names the syndrome “Malignant Gordon (?) Names the syndrome “Malignant Hyperthermia”Hyperthermia”Porcine Stress Syndrome related to MH Porcine Stress Syndrome related to MH

19711971 -- First International symposium on MH,Toronto First International symposium on MH,Toronto Caffeine contracture test identifiedCaffeine contracture test identifiedHalothane contracture test Halothane contracture test

1970s1970s -- Relation of masseter muscle rigidity to MHRelation of masseter muscle rigidity to MH

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Some Landmarks in theSome Landmarks in theEvolution of Understanding Evolution of Understanding

MHMH

19751975 -- Second International Symposium of MH, Denver Second International Symposium of MH, Denver Clinical presentation of MH Clinical presentation of MH Dantrolene as treatment for MHDantrolene as treatment for MH

19791979 -- FDA approval of Dantrolene FDA approval of Dantrolene

19811981 -- Formation of MHA and MHAUS Formation of MHA and MHAUS

19821982 -- MH hotline formed MH hotline formed

1980s1980s -- End tidal COEnd tidal CO22 as an early sign as an early sign

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Some Landmarks in the Some Landmarks in the Evolution of Understanding of Evolution of Understanding of

MHMH

1980s1980s: European and North American : European and North American

MH groups. Patient organizations MH groups. Patient organizations

North American MH Registry North American MH Registry

1990s1990s: Identification of ryanodine receptor gene as causal in : Identification of ryanodine receptor gene as causal in pigs, some humans pigs, some humans

1990s1990s: MH without anesthetics? : MH without anesthetics? More than 30 mutations are causal in humans More than 30 mutations are causal in humans

20002000- Introduction of molecular genetic testing - Introduction of molecular genetic testing

New tests proposed New tests proposed

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DefinitionDefinition

Malignant hyperthermia is a Malignant hyperthermia is a pharmacogeneticpharmacogenetic

disorder of skeletal muscle triggered in disorder of skeletal muscle triggered in

susceptiblessusceptibles (human or animal) (human or animal) in most instancesin most instances

by inhalation agents, and/or succinylcholine by inhalation agents, and/or succinylcholine

resulting in resulting in hypermetabolism, skeletal muscle hypermetabolism, skeletal muscle

damage, hyperthermia and death damage, hyperthermia and death if untreatedif untreated. .

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Trigger Agents for MHTrigger Agents for MH

MH Trigger AgentsMH Trigger Agents

Potent Volatile Potent Volatile Anesthetics (eg. Anesthetics (eg. halothane, halothane, sevoflurane, sevoflurane, desflurane) desflurane)

Succinylcholine Succinylcholine

Not MH TriggersNot MH Triggers

Intravenous agents Intravenous agents

Opioids Opioids

Non-depolarizing agents Non-depolarizing agents

Ketamine Ketamine

Propofol Propofol

Anxiolytics Anxiolytics

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Spectrum of Presentations of Spectrum of Presentations of Malignant HyperthermiaMalignant Hyperthermia

The classic case The classic case

Masseter muscle rigidity Masseter muscle rigidity

Associated with muscle disorders Associated with muscle disorders

MH without anesthesiaMH without anesthesia

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What are the Clinical What are the Clinical Manifestations of MH?Manifestations of MH?

Original ConceptsOriginal Concepts: :

All patients have muscle rigidity All patients have muscle rigidity

High fever, acidosis High fever, acidosis

High death rate High death rate

Current ConceptsCurrent Concepts

Muscle rigidity may or may not be present Muscle rigidity may or may not be present

Temperature is a late sign Temperature is a late sign

End tidal COEnd tidal CO22 is an early sign is an early sign

MH may occur at any point during anesthesia - or an emergence MH may occur at any point during anesthesia - or an emergence

Recrudescence despite treatmentRecrudescence despite treatment

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Signs of Malignant Signs of Malignant HyperthermiaHyperthermia

SpecificSpecific

– Muscle Rigidity Muscle Rigidity

– Increased COIncreased CO22

Production Production

– Rhabdomyolysis Rhabdomyolysis

– Marked Marked Temperature Temperature ElevationElevation

Non SpecificNon Specific

– Tachycardia Tachycardia

– Tachypnea Tachypnea

– Acidosis Acidosis (Resp/Metabolic) (Resp/Metabolic)

– Hyperkalemia Hyperkalemia

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Summary of Clinical SignsSummary of Clinical Signs

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10

5

% expired CO2

Acta Anaesthesiol Scand. 1984;28:1-8.

Marked increase in End-Tidal Marked increase in End-Tidal Carbon Dioxide in an MH crisisCarbon Dioxide in an MH crisis

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Metabolic Changes During MHMetabolic Changes During MH

0022 Consumption Consumption 3-5X Normal 3-5X Normal

PacoPaco22 59 +/- 4 59 +/- 4

Pvc0Pvc022 107 +/- 10 107 +/- 10

Pa 0Pa 022 142 +/- 10 142 +/- 10

Pv 0Pv 022 36 +/- 436 +/- 4

Gronert et al. CASJ. 1986.

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Death from MHDeath from MH

16 year old female 16 year old female

4 hour TM joint surgery 4 hour TM joint surgery

Forane and vecuronium Forane and vecuronium

Precipitous rise in end tidal COPrecipitous rise in end tidal CO2 2

Arrhythmias and cardiac arrest Arrhythmias and cardiac arrest

Temperature 42.2 C Temperature 42.2 C

Dantrolene, 10mg/kg Dantrolene, 10mg/kg

Died from DIC after two daysDied from DIC after two days

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Figure 2. Minute ventilation and end-tidal carbon dioxide versus time. The arrow denotes the administration of dantrolene. Time starts at induction of anesthesia (e.g., 0 = 8:00 am; 15 = 11:00 pm).

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12 15 0

20

40

60

80

100

10

15

20

Time (hrs)Time (hrs)

End-tidal CO2 Minute Ventilation 120

96300

5

Karan et al. Anes. Analg. 1996.

End-T

idal Carbon D

ioxide (mm

Hg

End-T

idal Carbon D

ioxide (mm

Hg

Min

ute

Ven

tilat

ion

(l/m

in)

Min

ute

Ven

tilat

ion

(l/m

in)

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Muscle Rigidity and MHMuscle Rigidity and MH

Jaw muscle rigidity may occur after succinylcholine Jaw muscle rigidity may occur after succinylcholine

More common in children More common in children

Presages MH in 20-30% Presages MH in 20-30%

Generalized rigidity not always present Generalized rigidity not always present

When present, regularly associated with MH When present, regularly associated with MH susceptibility susceptibility

With muscle breakdown and creatine kinase above With muscle breakdown and creatine kinase above 20,00IU, the likelihood of MH is very high.20,00IU, the likelihood of MH is very high.

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Incidence of MMRIncidence of MMR

Retrospective in ChildrenRetrospective in Children

Halothane/Succ.Halothane/Succ. 0.33-1.03% 0.33-1.03%

All AnesthesiaAll Anesthesia 0.12% 0.12%

Prospective in ChildrenProspective in Children

Halothane/Succ.Halothane/Succ. 0.9% 0.9%

Halo/STP/Succ.Halo/STP/Succ. 0.4% 0.4%

Retrospective - Adults and ChildrenRetrospective - Adults and Children

All AnestheticsAll Anesthetics 0.008%0.008%

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Disorders Associated with MH Disorders Associated with MH SusceptibilitySusceptibility

Central Core Disease Central Core Disease

Evans Myopathy Evans Myopathy

Hypokalemic Periodic Paralysis Hypokalemic Periodic Paralysis

?sodium channel myotonias ?sodium channel myotonias

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MHS mutations CCD mutations

transmembranedomains

4000 2000

T4826I

1 5038 aaI3916M

15364 pb

Y4796C

LS4647del

F4860del

RQF4214del

L4793P

I4898T

R4861H/C

R4893W

R4914G/T

G4899E/RG4638V

H4651P

G4907E

F4922L

Y4631N

R4825C

H4887Y

I4937M

T4637A

L4838V

A4906V

A4940TR4136S

V4234L

P4668SR4737W

P4973L

I403M

R552WR614C/L

C35R

G341R

G248RY522S

R401C/H

R163C/LD166N

R533C/H

R44C

R328W

R2163C/H/P

T2206M/R

R2435H/L

R2458C/H

G2434R/H

V2168M

R2454C/H

D2129E

V2214IE2347del

A2367T

D2431N

R2676W/T2787S

R2355W

R2401HR2428T

R2452W

V2117L

Mutations causing CCD are concentrated in the transmembrane domains of RYR1

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Mimics of Malignant HyperthermiaMimics of Malignant Hyperthermia

Fever (without rigidity)Fever (without rigidity) – Thyrotoxicosis Thyrotoxicosis – Sepsis Sepsis – Pheochromocytoma Pheochromocytoma – Iatrogenic overheating Iatrogenic overheating – Anticholinergic Anticholinergic

syndrome syndrome – Faulty equipment Faulty equipment – Tourniquet (children)Tourniquet (children)

Fever and muscleFever and muscle symptoms symptoms – NMSNMS – Hypoxic encephalopathy Hypoxic encephalopathy – Ionic contrast agents Ionic contrast agents

in CSF in CSF – Cocaine, amphetamine, Cocaine, amphetamine,

ecstasyecstasy

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Neurolept Malignant Neurolept Malignant SyndromeSyndrome

NMS is a potentially fatal, idiopathic NMS is a potentially fatal, idiopathic hypermetabolic response to a variety of hypermetabolic response to a variety of neuroleptics and dopamine receptor blocking neuroleptics and dopamine receptor blocking agentsagents. Although peripheral manifestations . Although peripheral manifestations include rhabdomyolysis and rigidity, the include rhabdomyolysis and rigidity, the pathophysiologic changes occur in the CNS pathophysiologic changes occur in the CNS Treatment with dantrolene, benzodiazepines, Treatment with dantrolene, benzodiazepines, dopamine agonists have been effectivedopamine agonists have been effective

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Principle Features of NMSPrinciple Features of NMS

Hypermetabolic response to potent neuroleptics Hypermetabolic response to potent neuroleptics and to dopamine receptor blocking drugs and to dopamine receptor blocking drugs

Incidence 0.2% of those taking Incidence 0.2% of those taking neuroleptics/antipsychotics neuroleptics/antipsychotics

Onset may be gradual or slow Onset may be gradual or slow

• Not inherited Not inherited

• No animal model No animal model

• Responsive to a variety of drug treatmentsResponsive to a variety of drug treatments

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Drugs that May Precipitate Drugs that May Precipitate NMSNMS

Antipsychotics ,e.g. phenothiazines,Resperidal, Olanzapine, Quietepine

Neuroleptics e.g. haloperidol, droperidol

Acute withdrawal of anti parkinson drugs

Dopamine blocking agents e.g. metoclopramide, promethazine, trifluoroperazine

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Pathophysiology of MHPathophysiology of MHand Molecular Geneticsand Molecular Genetics

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Muscle CellMuscle Cell

MitochondriaMitochondriat-Tubulest-Tubules MembraneMembrane

Sarcoplasmic reticulumSarcoplasmic reticulum

CalciumCalciumreleaserelease

channelschannels( )( )

Myofibrils (cause muscle contraction if CAMyofibrils (cause muscle contraction if CA2+2+ increases) increases)

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RyanodineRyanodinereceptorsreceptors

TerminalTerminalcisternaecisternae

t-tublet-tuble

TerminalTerminalcisternaecisternae

The TriadThe Triad

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DHPR

RYR1 Ca++

ATP

ADP

SERCA1

sarcomere

Ca++

ATP

ADP

Ca++

physiologic situation MH situation

+halothane

muscle contracture hypermetabolism

depolarisation

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Ryanodine receptor gene is a candidate Ryanodine receptor gene is a candidate for predisposition to malignant for predisposition to malignant

hyperthermiahyperthermia

David H. MacLennan*, Catherine DuffDavid H. MacLennan*, Catherine Duff††, , Francesco Zorzato*, Junichi Fujii*, Michael Francesco Zorzato*, Junichi Fujii*, Michael Phillips*, Robert G. KornelukPhillips*, Robert G. Korneluk‡‡, Wanda Frodis, Wanda Frodis§§, , Beverley A. BrittBeverley A. Britt§§ & Ronald G. Worton & Ronald G. Worton† †

Nature. V. 343; 1990.

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Identification of the Mutation in Porcine Identification of the Mutation in Porcine Ryanodine Receptor Associated with Malignant Ryanodine Receptor Associated with Malignant

HyperthermiaHyperthermia

JUNICHI FUJII,* KINYA OTSU, FRANCESCO ZORZATO,JUNICHI FUJII,* KINYA OTSU, FRANCESCO ZORZATO,†† STELLA STELLA DE LEON, VIJAY K. KHANNA, JANICE E. WEILER, PETER J. DE LEON, VIJAY K. KHANNA, JANICE E. WEILER, PETER J. O’BRIEN, DAVID H. MACLENNANO’BRIEN, DAVID H. MACLENNAN‡ ‡

Malignant hyperthermia (MH) causes neurological, liver, and kidney Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine damage and death in humans and major economic losses in the swine

industry. industry. A single point mutation in the porcine gene A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (for the skeletal muscle ryanodine receptor (ryr1ryr1) ) was found to be correlated with MH in five major was found to be correlated with MH in five major breeds of lean, heavily muscled swinebreeds of lean, heavily muscled swine.. Haplotyping Haplotyping suggests that the mutation in all five breeds has a common origin. suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs. MH gene or its controlled inclusion in swine breeding programs.

Science. 1991.

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Guidelines for Molecular Guidelines for Molecular Genetic Detection of Genetic Detection of

Susceptibility to Susceptibility to Malignant HyperthermiaMalignant Hyperthermia

Urwyler, A , Deufel T, McCarthy T et al Urwyler, A , Deufel T, McCarthy T et al

Br.J Anaesth. 86: 283,2001 Br.J Anaesth. 86: 283,2001

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European MHG GuidelinesEuropean MHG Guidelines

Probands Suspect MH relatives MH family members

Family history with causative MH mutation

negative

positive

Pt Referral for MH

IVCT

MH negative

positive

DNA testing

MH positive

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P & G – M Haus - 35

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MH Grading ScaleMH Grading Scale

Process IProcess I: Muscle Rigidity : Muscle Rigidity Generalized RigidityGeneralized Rigidity 15 15 Masseter RigidityMasseter Rigidity 15 15

Process IIProcess II: Myonecrosis : Myonecrosis Elevated CK>20,000 (+Succ.)Elevated CK>20,000 (+Succ.) 15 15 Elevated CK>20,000 (No Succ.)Elevated CK>20,000 (No Succ.) 15 15 Cola Colored UrineCola Colored Urine 10 10 Myoglobin in urine >60 ug/LMyoglobin in urine >60 ug/L 5 5 Blood/plasma/serum K>6 mEg/LBlood/plasma/serum K>6 mEg/L 3 3

Larach, et al. Anesthesiology. 80:771-779;1994.

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MH Grading Scale-IIMH Grading Scale-II

Process IIIProcess III: Respiratory Acidosis : Respiratory Acidosis PetCOPetCO22>55 with CV>55 with CV 15 15 PaCOPaCO22>60 with CV>60 with CV 15 15 PetCOPetCO22>60 with SV>60 with SV 15 15 Inappropriate hypercarbiaInappropriate hypercarbia 15 15 Inappropriate tachypneaInappropriate tachypnea 10 10

Process IVProcess IV: Temperature Increase : Temperature Increase Rapid increase in temperatureRapid increase in temperature 15 15 Inappropriate temperature >38.8Inappropriate temperature >38.8 10 10 in perioperative period in perioperative period

Process VProcess V: Cardiac Involvement : Cardiac Involvement Inappropriate tachycadriaInappropriate tachycadria 3 3

V. tach or V. fibV. tach or V. fib 3 3For a complete description, see:Larach M, Localio AR, Allen GC et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 1994;80 771-779

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What is the Incidence of MH?What is the Incidence of MH?

Original ConceptsOriginal Concepts: :

Rare. One in 50,000 anesthetics Rare. One in 50,000 anesthetics

Current ConceptsCurrent Concepts: :

Clinically based information:Clinically based information:

One in 20,000 to 50,000 anesthetics depending One in 20,000 to 50,000 anesthetics depending on drugs, population on drugs, population

Molecular Genetics based information:Molecular Genetics based information:

MH trait in 1 in 2,000-3,000 patients. Low MH trait in 1 in 2,000-3,000 patients. Low penetrance penetrance

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Diagnostic ProceduresDiagnostic Procedures

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What Tests Are UsedWhat Tests Are UsedTo Diagnose MH?To Diagnose MH?

Current Concepts:Current Concepts:

Halothane, caffeine contracture test (Halothane, caffeine contracture test (CHCTCHCT) is ) is

the only gold standard the only gold standard

Current InvestigationsCurrent Investigations: :

--Molecular genetics Molecular genetics

-Nuclear magnetic resonance for assessing ATP and creatine -Nuclear magnetic resonance for assessing ATP and creatine phosphate with/without exercise in vivo phosphate with/without exercise in vivo

-Calcium flux measurement in cultured muscle cells -Calcium flux measurement in cultured muscle cells

-Local increase in pC0-Local increase in pC022 following IM caffeine following IM caffeine

-EMG changes in MH patients-EMG changes in MH patients

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Muscle Contracture Muscle Contracture testingtesting

Expensive ( > $2500 ), invasive, non-routine Expensive ( > $2500 ), invasive, non-routine procedure done at specific diagnostic procedure done at specific diagnostic centers ( twelve in u.s.a. and canada ).centers ( twelve in u.s.a. and canada ).

Freshly biopsied skeletal muscle tissue.Freshly biopsied skeletal muscle tissue.

Muscle of choice is the vastus lateralis.Muscle of choice is the vastus lateralis.

2-3g muscle needed to perform TESTING2-3g muscle needed to perform TESTING

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Muscle- Bath Muscle- Bath ApparatusApparatus

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A.

B.

C.

Halothane 3%

Halothane 3%

Halothane 3%

1.4 g

1.5 g

1.2 g

2 min

HALOTHANE RESPONSE

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2.0mM 4.0 8.0

+0.3g +2.6g

2.0 mM 4.0

+0.8 +2.1g

Normal

MH Susceptible

Caffeine Dose ResponseCaffeine Dose Response

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Sensitivity and Specificity of Sensitivity and Specificity of Muscle Biopsy TestMuscle Biopsy Test

Sensitivity:Sensitivity: 100% 100%

Specificity:Specificity: 80%-80%-93% 93%

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Problems with Contracture Problems with Contracture TestTest

Fresh muscle needed: Fresh muscle needed: InvasiveInvasive

Difficult to standardize completely Difficult to standardize completely

Difficult to develop knowns and unknowns Difficult to develop knowns and unknowns

How to interpret in face of myopathy How to interpret in face of myopathy

Expensive!Expensive!

Few , widely scattered biopsy centers Few , widely scattered biopsy centers

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Other Tests Under Other Tests Under DevelopmentDevelopment

-Nuclear magnetic resonance for assessing -Nuclear magnetic resonance for assessing ATP and creatine phosphate with/without ATP and creatine phosphate with/without exercise in vivo exercise in vivo

-Calcium flux measurement in cultured -Calcium flux measurement in cultured muscle cells from needle biopsy with muscle cells from needle biopsy with caffeine caffeine

-Calcium flux in B lymphocytes with -Calcium flux in B lymphocytes with caffeine caffeine

-Local increase in pC0-Local increase in pC022 following IM caffeine following IM caffeine

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Treatment and Treatment and ManagementManagement

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Immediate TherapyImmediate Therapyof Malignant Hyperthermiaof Malignant Hyperthermia

Have a plan!Have a plan!

Discontinue inhalation agentsDiscontinue inhalation agents, ,

Hyperventilate with 100% 0Hyperventilate with 100% 02 2

BicarbonateBicarbonate 1-2 mg/kg as needed 1-2 mg/kg as needed

Get additional helpGet additional help

DantroleneDantrolene 2.5mg/kg Push. Repeat PRN 2.5mg/kg Push. Repeat PRN

Cool patientCool patient: gastric lavage, surface, wound : gastric lavage, surface, wound

Treat arrhythmias-Treat arrhythmias-do not use calcium channel blockers do not use calcium channel blockers

Arterial or venous blood gases Arterial or venous blood gases

Electrolytes, coagulation studiesElectrolytes, coagulation studies

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Dantrolene for MH CrisisDantrolene for MH Crisis

20 mg/60 ml = 1 mg/3ml 20 mg/60 ml = 1 mg/3ml

70 kg patient: 70 kg patient:

2.5 mg/kg2.5 mg/kg = 175 mg or 525 ml ( = 175 mg or 525 ml (99 vials) vials)

– –

~10 mg/kg = 700 mg or 2100 ml~10 mg/kg = 700 mg or 2100 ml (35 vials) (35 vials)

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Treatment of Malignant Treatment of Malignant HyperthermiaHyperthermia

Dantrolene-2 Dantrolene-2

After crisis controlled, give dantrolene 1mg/kg After crisis controlled, give dantrolene 1mg/kg every 4-6 hours for 24 hours every 4-6 hours for 24 hours

Continue dantrolene for 36 hours Continue dantrolene for 36 hours

Recrudescence rate is 25%Recrudescence rate is 25%

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Management of Malignant Management of Malignant HyperthermiaHyperthermia

Biochemical MarkersBiochemical Markers

Blood gases – esp pCOBlood gases – esp pCO22, pH, CK , pH, CK

Myoglobinuria Myoglobinuria

PT, PTT, INR, fibrin split products PT, PTT, INR, fibrin split products

Liver enzymes, BUNLiver enzymes, BUN

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Morbidity and MortalityMorbidity and Mortality

RHABDOMYOLYSIS RHABDOMYOLYSIS

RENAL FAILURERENAL FAILURE

DIC if temp >41.5DIC if temp >41.500 C C

Hyperkalemia Hyperkalemia

Acidosis Acidosis

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Prevention of Malignant Prevention of Malignant HyperthermiaHyperthermia

Preop personal/family history of anesthetic Preop personal/family history of anesthetic problems, neuromuscular disorders problems, neuromuscular disorders

Temperature/endtidal COTemperature/endtidal CO22 monitoring during monitoring during general anesthesia general anesthesia

Recognition of masseter rigidity Recognition of masseter rigidity

Investigation of unexplained tachycardia, Investigation of unexplained tachycardia, hypercarbia, hyperthermia hypercarbia, hyperthermia

Availability of Dantrolene Availability of Dantrolene

Avoiding MH triggers in MH susceptibles Avoiding MH triggers in MH susceptibles

Using Succinylcholine in indicationUsing Succinylcholine in indication

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Principles of Management ofPrinciples of Management ofMH SusceptibleMH Susceptible

Dantrolene not necessary Dantrolene not necessary preoperatively (dantrolene available) preoperatively (dantrolene available)

Avoid succinylcholine Avoid succinylcholine

Avoid potent inhalation agents Avoid potent inhalation agents

Discharge after about 2 hours in the Discharge after about 2 hours in the recovery room if all signs are stablerecovery room if all signs are stable

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Drug Safety in MHDrug Safety in MH

MH Trigger Agents MH Trigger Agents

Potent Volatile Potent Volatile Anesthetics (eg. Anesthetics (eg. halothane, halothane, sevoflurane, sevoflurane, desflurane) desflurane)

Succinylcholine Succinylcholine

Not MH Triggers Not MH Triggers

Intravenous agents Intravenous agents

Opioids Opioids

Non-depolarizing agents Non-depolarizing agents

Ketamine Ketamine

Propofol Propofol

Anxiolytics Anxiolytics

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SummarySummary

MH is a metabolic myopathy affecting skeletal muscle MH is a metabolic myopathy affecting skeletal muscle

All potent inhalation agents and Succinylcholine are the All potent inhalation agents and Succinylcholine are the triggers for MH triggers for MH

Inheritance of MH in humans is autosomal dominant Inheritance of MH in humans is autosomal dominant

The basic defect in MH is an increase in intracellular The basic defect in MH is an increase in intracellular calcium of the skeletal muscle calcium of the skeletal muscle

MH effects all ages and races MH effects all ages and races

MH appears to be more common in children than adultsMH appears to be more common in children than adults

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SummarySummary

Masseter muscle rigidity after Succinylcholine is Masseter muscle rigidity after Succinylcholine is associated with MH in 20-50% of cases associated with MH in 20-50% of cases

Endtidal COEndtidal CO22 increase is the most sensitive and specific increase is the most sensitive and specific clinical sign of MH clinical sign of MH

Although hyperthermia is a late sign of MH, it is an Although hyperthermia is a late sign of MH, it is an important confirmatory sign in some cases important confirmatory sign in some cases

Metabolic, respiratory acidosis are common Metabolic, respiratory acidosis are common

Myoglobinuria, elevation of CK are common during and Myoglobinuria, elevation of CK are common during and after MH after MH

MH may appear at any time during anesthesia and in MH may appear at any time during anesthesia and in the early part of the recovery periodthe early part of the recovery period

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SummarySummary

Prompt treatment with dantrolene 2.5mg/kg or more effectively Prompt treatment with dantrolene 2.5mg/kg or more effectively treats MH treats MH

Dantrolene should be continued for 24-48 hours Dantrolene should be continued for 24-48 hours

Sudden cardiac arrest in young males with inhalation agents +/- Sudden cardiac arrest in young males with inhalation agents +/- Succ often indicates hyperkalemia and occult myopathy Succ often indicates hyperkalemia and occult myopathy

Only accepted diagnostic test is the halothane-caffeine Only accepted diagnostic test is the halothane-caffeine contracture test contracture test

MH testing indicated in patients and clinical episodes and their MH testing indicated in patients and clinical episodes and their family members family members

Help and assistance are available from mhaus and Help and assistance are available from mhaus and the hotlinethe hotline

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STEPHANIE KULEBA

April 30, 2008 Wall Street Journal article "A Fresh Focus On a Rare Risk of Anesthesia" by Laura Landro.

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HAVE A PLAN AND MOVEHAVE A PLAN AND MOVE

Thank you