Case Discussion

17 y/o girl with congenital myopathy

RiRi 吳青芳 ╱ 吳青芳 ╱ SC SC 陳毓仁陳毓仁

Brief History-1 82 (7y/o): exercise difficulty82 (7y/o): exercise difficulty 86/10 (11y/o): scoliosis s/p Milwaukee brace at McKay 86/10 (11y/o): scoliosis s/p Milwaukee brace at McKay

Hospital Hospital 87/4 (12y/o): 87/4 (12y/o):

Progressive unsteady gait, dyspnea and consciousness Progressive unsteady gait, dyspnea and consciousness losslossCerebellar tumor with brainstem compression s/p Cerebellar tumor with brainstem compression s/p emergency tumor excision at McKay H.emergency tumor excision at McKay H.Tumor: vascular originTumor: vascular originPost-op: Post-op: failure to wean off ventilatorfailure to wean off ventilatorMuscle biopsy: Muscle biopsy: limb girdle myopathylimb girdle myopathyTracheostomy with ventilatorTracheostomy with ventilatorWheelchair-bound since then Wheelchair-bound since then

Brief History-2

88/9 (13y/o): 188/9 (13y/o): 1stst admission to NTUH for weaning admission to NTUH for weaning

Scoliosis at C-T spineScoliosis at C-T spine

Severe restrictive lung defect (FEV1 12.7%)Severe restrictive lung defect (FEV1 12.7%)

CK: 657 IU/LCK: 657 IU/L

Muscle biopsy: minimal histological changeMuscle biopsy: minimal histological change 89/2 (14y/o): Scoliosis correction at NCKU89/2 (14y/o): Scoliosis correction at NCKU 92/3 (17y/o): 92/3 (17y/o):

Bil. Hamstring & Achilles tendon release at NCKUBil. Hamstring & Achilles tendon release at NCKU

Then walked by side barThen walked by side bar

Brief History-3 92/9: 292/9: 2ndnd admission to NTUH for abd. pain, poor appetite, admission to NTUH for abd. pain, poor appetite,

episodes of desaturation occurredepisodes of desaturation occurred

92/10/31:92/10/31: GastrostomyGastrostomy due to dysphagia (poor swallow function), due to dysphagia (poor swallow function),

silent aspiration & upper esophageal swellingsilent aspiration & upper esophageal swelling

92/12/3: 92/12/3: Gastrostomy revision due to wound discharge & leakageGastrostomy revision due to wound discharge & leakage Hickmann catheter insertionHickmann catheter insertion

92.10.31 92.12.03

Pre-op Evaluation

Congenital myopathy (limb girdle myopathy?)Congenital myopathy (limb girdle myopathy?) mild muscle weakness over bilateral lower limbsmild muscle weakness over bilateral lower limbs scoliosis s/p operationscoliosis s/p operation mild oropharyngeal dysphagia with silent aspirationmild oropharyngeal dysphagia with silent aspiration hypercapneic respiratory failure s/p tracheostomyhypercapneic respiratory failure s/p tracheostomy

severe restrictive lung defect (FEVsevere restrictive lung defect (FEV11 12.7%) 12.7%)

normal cardiac function (LVEF 83% in 88/11)normal cardiac function (LVEF 83% in 88/11) unproved muscle biopsyunproved muscle biopsy Joint contracture s/p operationJoint contracture s/p operation Cerebellar tumor s/p excisionCerebellar tumor s/p excision

Anesthesia Method92/12/392/12/3 92/10/3192/10/31

InductionInduction SevofluraneSevoflurane Fentanyl 10mlFentanyl 10ml

Esmeron 10mg (0.4mg/kg)Esmeron 10mg (0.4mg/kg)

Atropine 0.4mgAtropine 0.4mg

SevofluraneSevoflurane

IntubationIntubation TracheostomyTracheostomy TracheostomyTracheostomy

MaintenanceMaintenance SevofluraneSevoflurane

Niabex (cisatracurium) Niabex (cisatracurium) 4mg (0.16mg/kg)4mg (0.16mg/kg)

SevofluraneSevoflurane

Esmeron 10mg (0.4mg/kg) Esmeron 10mg (0.4mg/kg)

NM NM blockade blockade reversalreversal

AtropineAtropine

Enlon (edrophonium)Enlon (edrophonium)

Discussion

Diseases of Skeletal Muscle

Denervation atrophyDenervation atrophy Muscular dystrophyMuscular dystrophy Myotonic dystrophyMyotonic dystrophy Ion channel myopathyIon channel myopathy Congenital myopathyCongenital myopathy Inflammatory myopathyInflammatory myopathy Toxic myopathyToxic myopathy Disease of neuromucular junctionDisease of neuromucular junction

Robbins, Pathological basis of disease, 1999

Muscular dystrophy

Muscular dystrophy is a heterogeneous Muscular dystrophy is a heterogeneous group of hereditary noninflammatory but group of hereditary noninflammatory but progressive muscle disorders without a progressive muscle disorders without a central or peripheral nerve abnormality.central or peripheral nerve abnormality.

It’s clinically characterized by It’s clinically characterized by progressive muscle weakness and progressive muscle weakness and wasting. wasting.

Muscular dystrophyClassification

Sex-linked MDs Sex-linked MDs Duchenne Duchenne 1010 ～～ 30 per 100,00030 per 100,000 Becker Becker 3 per 100,0003 per 100,000 Emery-DreifussEmery-Dreifuss 1 per 100,0001 per 100,000

Autosomal dominant MDs Autosomal dominant MDs Fascioscapulohumeral Fascioscapulohumeral Distal, Ocular, OculopharyngealDistal, Ocular, Oculopharyngeal

Autosomal recessive MDsAutosomal recessive MDs Congenital muscular dystrophy (CMD) Congenital muscular dystrophy (CMD) 7~12 per 100,0007~12 per 100,000

Pure CMDPure CMD Fukuyama CMD Fukuyama CMD Finnish-type CMD Finnish-type CMD Walker-WarburgWalker-Warburg

Limb girdle muscular dystrophy, LGMD ( both AD & AR )Limb girdle muscular dystrophy, LGMD ( both AD & AR )

only accounts for 1.3% of patients with muscular dystrophyonly accounts for 1.3% of patients with muscular dystrophy

Muscular dystrophyCongenital

Duchenne, Becker

Emery-Dreifuss

Limb girdle

Muscular dystrophy Clinical manifestations

Duchenne muscular dystrophyDuchenne muscular dystrophy Dystrophin gene mutation (at Xp21)Dystrophin gene mutation (at Xp21) No abnormality is noted in the patient at birthNo abnormality is noted in the patient at birth The symptoms appear at the age of 2~6 yr, and The symptoms appear at the age of 2~6 yr, and

patients are usually wheelchair-bound by 10 yr.patients are usually wheelchair-bound by 10 yr. Rapidly progressiveRapidly progressive Not only skeletal muscle but also cardiac and Not only skeletal muscle but also cardiac and

smooth musclesmooth muscle Death occurs late in the second decade from Death occurs late in the second decade from

respiratory complications in over 90% of casesrespiratory complications in over 90% of cases

Muscular dystrophy Clinical manifestations

BeckerBecker Similar to Duchenne. Because they still have Similar to Duchenne. Because they still have

some functioning dystrophin, the symptoms may some functioning dystrophin, the symptoms may occur later and are more mild.occur later and are more mild.

Emery-DreifussEmery-Dreifuss Mutation of the X chromosome in the emerin geneMutation of the X chromosome in the emerin gene Typically presents at the age of 4~5 years with Typically presents at the age of 4~5 years with

contractures of the elbows, Achilles tendon contractures of the elbows, Achilles tendon (causing toe walking) and posterior cervical (causing toe walking) and posterior cervical musclemuscle.. Cardiomyopathy usually presenting as Cardiomyopathy usually presenting as heart block, heart block, result in sudden deathresult in sudden death

Muscular dystrophy Clinical manifestations

Limb girdle muscular dystrophy (LGMD)Limb girdle muscular dystrophy (LGMD) Originally it’s a diagnosis of exclusion, with Originally it’s a diagnosis of exclusion, with

symptoms of progressive proximal muscular symptoms of progressive proximal muscular dystrophy. Now it’s reclassified recording to dystrophy. Now it’s reclassified recording to genetic basis. At least 13 different types can be genetic basis. At least 13 different types can be recognized now.recognized now.

Autosomal dominant typeAutosomal dominant type Autosomal recessive typeAutosomal recessive type

One gene with different phenotypes, one One gene with different phenotypes, one phenotype with different genesphenotype with different genes

General principlesGeneral principles More sensitive to the myocardial depressant More sensitive to the myocardial depressant

effects of potent inhaled anestheticseffects of potent inhaled anesthetics Succinylcholine is contraindicated because Succinylcholine is contraindicated because

massive rhabdomyolysis, hyperkalemia, and massive rhabdomyolysis, hyperkalemia, and cardiac arrest can occurcardiac arrest can occur

Sensitive to nondepolarizing muscle relaxants, Sensitive to nondepolarizing muscle relaxants, they may require a longer recovery timethey may require a longer recovery time

Vigorous respiratory therapy and ventilatory Vigorous respiratory therapy and ventilatory support may be necessary.support may be necessary.

Muscular dystrophy Anesthetic considerations

In Duchenne muscular dystrophy (1)In Duchenne muscular dystrophy (1) Obesity is most commonObesity is most common Hypertrophy of the tongue, difficult intubationHypertrophy of the tongue, difficult intubation Deformities and contractures of the limb joints that Deformities and contractures of the limb joints that

will hinder vascular access and also positioningwill hinder vascular access and also positioning Spinal deformity may compress the upper Spinal deformity may compress the upper

respiratory tractrespiratory tract Compromised respiratory functionCompromised respiratory function Heart, persistent sinus tachycardia, arrhythmias, Heart, persistent sinus tachycardia, arrhythmias,

nonspecific murmursnonspecific murmurs

Muscular dystrophy Anesthetic considerations

In Duchenne muscular dystrophy (2)In Duchenne muscular dystrophy (2) The use of halothane, isoflurane, sevoflurane and The use of halothane, isoflurane, sevoflurane and

succinylcholine in DMD child can result in acute succinylcholine in DMD child can result in acute rhabdomyolysis, hyperkalemia. rhabdomyolysis, hyperkalemia.

The use of Vecuronium in DMD there can be up to The use of Vecuronium in DMD there can be up to sixfold delay in the recovery of muscle function. sixfold delay in the recovery of muscle function. Atracurium is currently the drug of choice. Atracurium is currently the drug of choice.

The association of DMD with malignant The association of DMD with malignant hyperthermia is not proven. Prophylactic use of hyperthermia is not proven. Prophylactic use of dantrolene in known DMD patients may be dantrolene in known DMD patients may be considered. considered.

Muscular dystrophy Anesthetic considerations

In Emery-Dreifuss muscular dystrophyIn Emery-Dreifuss muscular dystrophy Cardiac involvementCardiac involvement ：： atrial standstill is a atrial standstill is a

pathognomonic finding, with a lack of atrial pathognomonic finding, with a lack of atrial response to intracardiac electrical or mechanical response to intracardiac electrical or mechanical stimulation. stimulation.

Neck stiffnessNeck stiffness Flexion contracturesFlexion contractures Muscle involvementMuscle involvement ：： succinylcholine is succinylcholine is

contraindicatedcontraindicated

Muscular dystrophy Anesthetic considerations

Myotonic dystrophy( dytrophia myotonica, DM )

The most frequently inherited The most frequently inherited neuromuscular disease of adult lifeneuromuscular disease of adult life

It is a multisystem disease with major It is a multisystem disease with major cardiac involvementcardiac involvement

Core features of myotonic dystrophy are Core features of myotonic dystrophy are myotonia, muscle weakness, cataract, myotonia, muscle weakness, cataract, and cardiac conduction abnormalitiesand cardiac conduction abnormalities

Myotonic dystrophyClassification

Type 1 (most common, 98%)Type 1 (most common, 98%) an expansion of CTG repeats in the DMPK gene an expansion of CTG repeats in the DMPK gene

on chromosome 19on chromosome 19 Prevalence in West: 13.5 per 100,000Prevalence in West: 13.5 per 100,000

Type 2Type 2 an expansion of CCTG repeats in the ZNF9 gene an expansion of CCTG repeats in the ZNF9 gene

on chromosome 3on chromosome 3

Type 3 ?Type 3 ?

Myotonic dystrophy Clinical manifestations

Ptosis and weakness of the facial, jaw, and anterior Ptosis and weakness of the facial, jaw, and anterior neck muscles, distal weakness of the limbs neck muscles, distal weakness of the limbs progressing to proximal weaknessprogressing to proximal weakness

MyotoniaMyotonia CataractsCataracts Cardiac involvement is characterised by progressive Cardiac involvement is characterised by progressive

conduction system abnormalities, supraventricular conduction system abnormalities, supraventricular and ventricular arrhythmias and, less frequently, and ventricular arrhythmias and, less frequently, myocardial dysfunction and ischaemic heart disease.myocardial dysfunction and ischaemic heart disease.

Type 1 and type 2 are similarType 1 and type 2 are similar

Heart: progressive conduction system abnormalitiesHeart: progressive conduction system abnormalities Halothane will delay conduction in His-Purkinje Halothane will delay conduction in His-Purkinje

system and should be avoidedsystem and should be avoided Mitral regurgitation is commonMitral regurgitation is common Lung: restrictive lung disease, and diminished Lung: restrictive lung disease, and diminished

ventilatory responses to hypoxia and hypercapniaventilatory responses to hypoxia and hypercapnia Thiopental and Etomidate are safe to useThiopental and Etomidate are safe to use Propofol as an induction and maintenance agent is Propofol as an induction and maintenance agent is

controversialcontroversial

Myotonic dystrophyAnesthetic considerations

(1)

Particularly sensitive to succinylcholine, the Particularly sensitive to succinylcholine, the development of myotonia may result in difficult development of myotonia may result in difficult intubation and ventilationintubation and ventilation

Non-depolarizing MR usually have normal or Non-depolarizing MR usually have normal or prolonged response, and the reversal of MR may be prolonged response, and the reversal of MR may be needed. But the anticholinesterases may precipitate needed. But the anticholinesterases may precipitate myotonia, presumably a result of increased sensitivity myotonia, presumably a result of increased sensitivity to Ach. Short-acting MR are recommendedto Ach. Short-acting MR are recommended

The response to a peripheral nerve stimulator must The response to a peripheral nerve stimulator must be carefully interpreted because muscle stimulation be carefully interpreted because muscle stimulation may trigger myotoniamay trigger myotonia

Cold is a potent trigger of myotonia episodesCold is a potent trigger of myotonia episodes

Myotonic dystrophyAnesthetic considerations

(2)

Congenital myopathy

Congenital myopathy is a term for any muscle Congenital myopathy is a term for any muscle disorder present at birthdisorder present at birth

Unique morphological features on Unique morphological features on histochemical or ultrastructural examination of histochemical or ultrastructural examination of a muscle biopsy a muscle biopsy

Present in early life or infancy with proximal Present in early life or infancy with proximal or generalized hypotonia and weaknessor generalized hypotonia and weakness

Often with dysmorphic features Often with dysmorphic features Relatively nonprogressiveRelatively nonprogressive

Congenital myopathyClassification

Nemaline (rod) myopathy (20%) Nemaline (rod) myopathy (20%) incidence about 2 per 100,000incidence about 2 per 100,000 Central core disease (16%) Central core disease (16%) Centronuclear (myotubular) myopathy (14%) Centronuclear (myotubular) myopathy (14%) Multi-minicore myopathy (10%) Multi-minicore myopathy (10%) Fiber type disproportion or type 1 fiber predominance (21%) Fiber type disproportion or type 1 fiber predominance (21%) Miscellaneous congenital myopathies (19%)Miscellaneous congenital myopathies (19%)

Fingerprint body myopathyFingerprint body myopathy Reducing body myopathyReducing body myopathy Sarcotubular myopathy Sarcotubular myopathy Hyaline body myopathy Hyaline body myopathy Trilaminar fiber myopathy Trilaminar fiber myopathy Cap myopathy Cap myopathy Zebra body myopathy Zebra body myopathy Spheroid body myopathy Spheroid body myopathy Cytoplasmic body myopathyCytoplasmic body myopathy Desmin storage myopathies Desmin storage myopathies

Nemaline (rod) myopathy

Facial & Axial weakness (severe)Facial & Axial weakness (severe) High-arched narrow palate (severe)High-arched narrow palate (severe) Distal weakness & contracturesDistal weakness & contractures Deaths due to respiratory insufficiencyDeaths due to respiratory insufficiency

Gomori trichrome (GT) stain,

Skeletal muscle

Central core myopathy

Dominant inheritance: Often Dominant inheritance: Often History of malignant hyperthermia in History of malignant hyperthermia in

family (Ryanodine receptor, RYR 1)family (Ryanodine receptor, RYR 1) Proximal weaknessProximal weakness Relatively non-progressiveRelatively non-progressive

Nicotinamide adenine dinucleotide (NADH) stain, Skeletal muscle

Centronuclear myopathy

Onset: infancy, early death (5 months)Onset: infancy, early death (5 months) EOM limitation, ptosisEOM limitation, ptosis Respiratory failureRespiratory failure Weakness non-progressiveWeakness non-progressive

↑H&E stain

← Trichrome stain

Nemaline Myopathy Anesthetic considerations(1) Facial dysmorphismFacial dysmorphism: difficult intubation: difficult intubation Inhalation induction, awake intubation or use Inhalation induction, awake intubation or use

of fiberoptic bronchoscopeof fiberoptic bronchoscope Restrictive pulmonary defectRestrictive pulmonary defect: due to : due to

myopathy and scoliosis, confirmed by myopathy and scoliosis, confirmed by spirometry, tracheal extubation after fully spirometry, tracheal extubation after fully awake and responsiveawake and responsive

The question of The question of which anesthetic agent which anesthetic agent may be used safelymay be used safely

  Stephen & Heard, 1983

Mary & Frederick, 1985

Mary & Frederick, 1985

T. Asai, 1992

Pre-op evaluation 18 y/o woman, severe restrictive lung

13 y/o girl, severe restrictive lung, minor facial dysmorphism

14 y/o girl, severe restrictive lung, narrow mandible, high-arched palate

2 y/o boy, high-arched palate, pneumonia episode

Op purpose repair of prognathic malocclusion

correction of scoliosis correction of scoliosis ASD repair

Intubation nasally deep halothane posterior arythenoid, stylet

 

Induction fentanyl 1μg/kg iv, thiopental 4mg/kg iv, nitrous oxide 66%, oxygen 34%

thiopentone 5mg/kg, atropine 0.02mg/kg

nitrous oxide, oxygen, halothane

diazepam 2mg, fentanyl 200μg, pancuronium 2 mg

Maintenance nitrous oxide/ oxygen/ enflurane (1.0% ET conc.) + fentanyl + intermittent pancuronium (total dose 0.18mg/kg)

fentanyl + halothane nitrous oxide, oxygen, isoflurane

high-dose fentanyl + diazepam

NM blockade monitor single twitch every 10 sec

     

Muscle relaxant SuccinylcholinePancuronium

no no Pancuronium

NM blockade reversal atropine 0.02mg/kg, neostigmine 0.06mg/kg iv

     

Nemaline Myopathy Anesthetic considerations(2) Resistance to succinylcholine (1mg/kg) under normal

pseudocholinesterase, no fasciculation, phase block or Ⅱhyperkalemia

Response to pancuronium (0.08mg/kg) and neostigmine were normal

From Stephen and Heard,1983

Patients can be safely managed without use of muscle relaxant

No reported association with malignant hyperthermia From Mary and Frederick, 1985

Muscle relaxant should be administered in cardiac surgery with high-dose fentanyl anesthesia, to control rigidity, to facilitate intubation and to prevent movement

From T. Asai, 1992

Centronuclear Myopathy Anesthetic considerations(1)

  Allan&Terry, 1998 D. Breslin, 2000 Euro. J. of Anes., 2002

Pre-op evaluation

32y/o womanrestrictive lung & asthma, GERD, TMJ limited movement

53y/o manPEV1 70%

20y/o maneasy choking with progressive deformity of jaw, ASA grade Ⅲs/p tracheostomy

Op purpose Arthroplasty of TMJ Tibial nail insertion Correction of deformity of maxilla and mandible

Premedication

Glycopyrrolate    

Induction propofol Propofol, remifentanil Propofol, remifentanil

Intubation Topical lidocaine & superior laryngeal nerve block→nasal fiberoptic

smoothly Pre-existing tracheostomy

Maintenance Propofol, nitrous oxide, oxygenSurgical site: bupivacaine

Profopol, remifentanil infusion & 60% N2O

Propofol, remifentanil

Centronuclear Myopathy Anesthetic considerations(2) Depolarizing muscle relaxant is avoidedDepolarizing muscle relaxant is avoided Volatile anesthetics were avoided because of the risk Volatile anesthetics were avoided because of the risk

of developing MH.of developing MH. The combination of propofol and remifentanil The combination of propofol and remifentanil

infusions allowed smooth induction, easy intubation infusions allowed smooth induction, easy intubation and ventilation, intra-op hemodynamic stability and and ventilation, intra-op hemodynamic stability and early recovery and extubation with minimal residual early recovery and extubation with minimal residual effects.effects.

It is important to monitor NM function before the It is important to monitor NM function before the administration of muscle relaxants.administration of muscle relaxants.

From Allen & Terry, 1998, D.Breslin & J.Reid, 2000From Allen & Terry, 1998, D.Breslin & J.Reid, 2000

In this case

Assess intubation difficultyAssess intubation difficulty tracheostomy already Pulmonary function testPulmonary function test severe restrictive lung defect Risk of aspirationRisk of aspiration tracheostomy, atropine Anesthetic drug of choiceAnesthetic drug of choice Nondepolarizing MR: rocuronium, cisatracurium Sevoflurane reversal of block: atropine and edrophonium

Conclusion Pre-op evaluationPre-op evaluation

Assess intubation difficultyAssess intubation difficulty

Look for cardiac conduction abnormalityLook for cardiac conduction abnormality

Do pulmonary function testDo pulmonary function test

Risk of aspirationRisk of aspiration

Anesthetic drugAnesthetic drug

Avoid SCC, volatile anestheticAvoid SCC, volatile anesthetic

Try low dose & short acting nondepolarizing muscle Try low dose & short acting nondepolarizing muscle relaxantsrelaxants

Thanks for your attention!

Let’s go to OR!