Muscle Disorders Muscle Disorders and General and General AnaestheticsAnaestheticsBen Creagh-Brown, UHLBen Creagh-Brown, UHL

May 2004May 2004

Muscle disease (Myopathy ) Muscle disease (Myopathy ) can be divided intocan be divided into

Myositis – inflammatory diseaseMyositis – inflammatory disease Muscular dystrophy – inherited Muscular dystrophy – inherited

disorder with progressive weaknessdisorder with progressive weakness Myotonia - sustained contraction Myotonia - sustained contraction

and slow relaxationand slow relaxation Channelopathies – disorders of ion Channelopathies – disorders of ion

channels within skeletal muscle cellschannels within skeletal muscle cells

3 main groups to be 3 main groups to be consideredconsidered

Myasthenia Gravis and LEMSMyasthenia Gravis and LEMS Duchenne’s and Becker’s Muscular Duchenne’s and Becker’s Muscular

DystrophyDystrophy Myotonic dystrophyMyotonic dystrophy

Myasthenia Gravis and Myasthenia Gravis and LEMSLEMS

A 25 year old female presents for A 25 year old female presents for thymectomy for myasthenia gravisthymectomy for myasthenia gravis

1.1. What is myasthenia gravis?What is myasthenia gravis?2.2. Tell me as much as you know about itTell me as much as you know about it3.3. How is it diagnosed? (include EMG)How is it diagnosed? (include EMG)4.4. What is edrophonium?What is edrophonium?5.5. How does it work?How does it work?6.6. What dose should be used?What dose should be used?7.7. What are the symptoms?What are the symptoms?8.8. How would you anaesthetise her?How would you anaesthetise her?

DescriptionDescription Myasthenia Gravis (MG) is an autoimmune Myasthenia Gravis (MG) is an autoimmune

condition in which IgG autoantibodies condition in which IgG autoantibodies interact with the postsynaptic acetylcholine interact with the postsynaptic acetylcholine receptors (AChR) at the nicotinic receptors (AChR) at the nicotinic neuromuscular junction (NMJ).neuromuscular junction (NMJ).

The AChR antibodies reduce the number of The AChR antibodies reduce the number of functional receptors by:functional receptors by: blocking attachment of ACh moleculesblocking attachment of ACh molecules increasing the rate of degeneration of the increasing the rate of degeneration of the

receptorsreceptors complement-induced damage to the NMJ. complement-induced damage to the NMJ.

On average MG patients have 30% of the On average MG patients have 30% of the normal number of functional AChR.normal number of functional AChR.

IncidenceIncidence

AgeAge

SexSex

Aetiology and Aetiology and associationsassociations

PathologyPathology

1 in 10,000 of the population

Two peaks: 20-30 years in women and 60-70 years in men.

Twice as common in women

Acquired autoimmune disease of unknown cause. Can be a result of D-penicillamine treatment for rheumatoid arthritis.Associated with other organ-specific autoimmune diseases

Thymic hyperplasia is found in 70% of patients below 40 years. 10% have a thymoma, increasing inc. with age.Young patients without a thymoma have increased association with HLA B8 and DR3.

Clinical featuresClinical features

ComplicationsComplications

PrognosisPrognosis

Progressive weakness and Progressive weakness and fatiguability of voluntary muscle, fatiguability of voluntary muscle, particularly ocular, proximal limb, particularly ocular, proximal limb, bulbar and facial muscles. bulbar and facial muscles. Myocardium never involved. Myocardium never involved. Fatiguability is weakness accentuated Fatiguability is weakness accentuated by exercise and relieved with rest.by exercise and relieved with rest.

Respiratory failure. Aspiration from Respiratory failure. Aspiration from bulbar palsy. bulbar palsy.

Normal or nearly normal lives. Some Normal or nearly normal lives. Some case of myasthenia gravis may go into case of myasthenia gravis may go into remission temporarily. In a few cases, remission temporarily. In a few cases, the severe weakness of myasthenia the severe weakness of myasthenia gravis may cause respiratory failure.gravis may cause respiratory failure.

InvestigationsInvestigations

AntibodiesAntibodies

ElectromyogramElectromyogram

Tensilon testTensilon test

Serum AchR antibodies can be found Serum AchR antibodies can be found in 90% of generalised MG, not likely in 90% of generalised MG, not likely to be found in pure ocular disease. to be found in pure ocular disease. PathognomicPathognomic

Electromyography (EMG). Compound Electromyography (EMG). Compound muscle action potentials (CMAP) muscle action potentials (CMAP) shows that repetitive stimulation shows that repetitive stimulation results in progressive decrease in results in progressive decrease in CMAP = fade. These findings are not CMAP = fade. These findings are not specific.specific.

Edrophonium (tensilon) test. 10mg of Edrophonium (tensilon) test. 10mg of this anticholinesterase is given IV as a this anticholinesterase is given IV as a bolus (after a 1-2mg test dose). bolus (after a 1-2mg test dose). Improvements in weakness happen Improvements in weakness happen within 30 s and lasts for up to 5 mins. within 30 s and lasts for up to 5 mins. Test dose is because it can cause Test dose is because it can cause bronchoconstriction and syncope.bronchoconstriction and syncope.

TreatmentsTreatments

Anticholinesterase Anticholinesterase treatmenttreatment

ImmunosuppressionImmunosuppression

Plasma exchange Plasma exchange and immunoglobulinand immunoglobulin

ThymectomyThymectomy

To enhance NMJ transmission by To enhance NMJ transmission by delaying degradation of Ach. delaying degradation of Ach. Pyridostigmine is the most commonly Pyridostigmine is the most commonly used drug. Acts within 30 mins and used drug. Acts within 30 mins and lasts for 4 hours. Initially works well lasts for 4 hours. Initially works well but effective diminishes over months. but effective diminishes over months.

Immunosuppression with prednisolone Immunosuppression with prednisolone or azathioprine. Start high and taper or azathioprine. Start high and taper downdown

Inducing remission of myasthenic Inducing remission of myasthenic crises or pre-op before thymectomy. crises or pre-op before thymectomy. Both work within days IV Ig has a Both work within days IV Ig has a longer effect. longer effect.

Thymectomy if thymoma either by Thymectomy if thymoma either by sternotomy or mediastinoscopy. Can sternotomy or mediastinoscopy. Can do thymectomy for thymic hyperplasia do thymectomy for thymic hyperplasia aiming to induce remission – these aiming to induce remission – these may take a long time.may take a long time.

PyridostigminePyridostigmine Analogue of neostigmineAnalogue of neostigmine More effectively absorbed from the gutMore effectively absorbed from the gut With equipotent doses, pyridostigmine With equipotent doses, pyridostigmine

has a slower onset and longer duration has a slower onset and longer duration of action, and produces fewer of action, and produces fewer gastrointestinal side effects than gastrointestinal side effects than neostigmineneostigmine

Patients may get the side effects of Patients may get the side effects of diarrhoea and abdominal cramps so they diarrhoea and abdominal cramps so they take atropine 0.5mg with each dosetake atropine 0.5mg with each dose

Anaesthetic managementAnaesthetic management

1.1. Avoid drugs that exacerbate MGAvoid drugs that exacerbate MG polymyxin antibiotics (such as colistin) polymyxin antibiotics (such as colistin)

block AChR but are rarely used anywayblock AChR but are rarely used anyway AminoglycosidesAminoglycosides decrease Ach release decrease Ach release

and AChR sensitivity and should be and AChR sensitivity and should be avoidedavoided

Procainamide exacerbate weaknessProcainamide exacerbate weakness Quinine exacerbate weaknessQuinine exacerbate weakness Beta blockersBeta blockers exacerbate weakness exacerbate weakness

Pre operative assessmentPre operative assessment Assessment of respiratory function (serial FVC on the Assessment of respiratory function (serial FVC on the

ward) and bulbar weakness (SALT)ward) and bulbar weakness (SALT) Chest physiotherapyChest physiotherapy Optimise immunosuppression and anticholinesterase Optimise immunosuppression and anticholinesterase

therapytherapy Consider IV Ig or plasma exchangeConsider IV Ig or plasma exchange Consider ITU bed, prolonged ventilation post op more Consider ITU bed, prolonged ventilation post op more

likely if:likely if: Stage III or IV diseaseStage III or IV disease Chronic respiratory diseaseChronic respiratory disease FVC <2.9lFVC <2.9l Long history of disease (>6 years)Long history of disease (>6 years)

Exclude associated thyroid disease or DMExclude associated thyroid disease or DM Airway ?RA ?Thymic mass compressingAirway ?RA ?Thymic mass compressing

On day of operationOn day of operation

Give anticholinesterases or not? Give anticholinesterases or not? Why?Why?

Omit anticholinesterase therapy as Omit anticholinesterase therapy as this may prolong action of sux, this may prolong action of sux, require increased doses of non require increased doses of non depolarising meuromuscular depolarising meuromuscular blocking drugsblocking drugs

Increased steroids, IV Increased steroids, IV hydrocortisone hydrocortisone

Induction and Induction and maintenancemaintenance

Consider IABP as well as routine monitoring if sternotomyConsider IABP as well as routine monitoring if sternotomy Continuously monitor NM blockadeContinuously monitor NM blockade Intubate – need to protect the airway. Consider Intubate – need to protect the airway. Consider

nasotracheal intubation if planned postop ventilation.nasotracheal intubation if planned postop ventilation. Some anaesthetists avoid IV induction and paralysis but Some anaesthetists avoid IV induction and paralysis but

intubate after deepening with inhalational agents only, intubate after deepening with inhalational agents only, MG patients are more susceptible to the muscle relaxant MG patients are more susceptible to the muscle relaxant effect of volatile. effect of volatile.

You may require more sux that usual and consequently get You may require more sux that usual and consequently get a Phase II blocka Phase II block

Conversely they are exquisitely sensitive to non Conversely they are exquisitely sensitive to non depolarising neuromuscular blocking drugs (NDNMB) Use depolarising neuromuscular blocking drugs (NDNMB) Use 30-40% of the usual dose of vecuronium or atracurium.30-40% of the usual dose of vecuronium or atracurium.

Avoid reversing the NDNMB drugs to avoid the risk of Avoid reversing the NDNMB drugs to avoid the risk of cholinergic crisischolinergic crisis

Post operativePost operative

Majority can be safely extubated and Majority can be safely extubated and go back to the wardgo back to the ward

HDU may be appropriateHDU may be appropriate ITU if ventilation requiredITU if ventilation required Good analgesia including opiates.Good analgesia including opiates.

LEMSLEMS Lambert-Eaton Myasthenic Syndrome - a rare syndrome Lambert-Eaton Myasthenic Syndrome - a rare syndrome

occurring in association with small cell carcinoma of the occurring in association with small cell carcinoma of the bronchus. bronchus.

LEMS results from an autoimmune attack directed against the LEMS results from an autoimmune attack directed against the Voltage Gated Calcium Channels (VGCC) on the presynaptic Voltage Gated Calcium Channels (VGCC) on the presynaptic motor nerve terminal (in 98% of those with cancer)motor nerve terminal (in 98% of those with cancer)

Antibodies have been found in the majority of patients with Antibodies have been found in the majority of patients with LEMS. LEMS.

3% of patients with SSLC.3% of patients with SSLC. Clinical features similar to MG but facial and bulbar muscles Clinical features similar to MG but facial and bulbar muscles

relatively sparedrelatively spared Distinguishing between the two diseases on EMG: Facilitation Distinguishing between the two diseases on EMG: Facilitation

(strength improvement after exercise) is common in LEMS. (strength improvement after exercise) is common in LEMS. Facilitation differentiates the 2 diseases only if it is noted after Facilitation differentiates the 2 diseases only if it is noted after repeated testing of many separate muscle groupsrepeated testing of many separate muscle groups

They improve with the edrophonium test but not as markedlyThey improve with the edrophonium test but not as markedly Very sensitive to both depolarising and non depolarising drugsVery sensitive to both depolarising and non depolarising drugs

There are other rare myasthenic syndromes including There are other rare myasthenic syndromes including congenitalcongenital

Duchenne’s Muscular Duchenne’s Muscular DystrophyDystrophy

X linked recessive disorder, A third of cases X linked recessive disorder, A third of cases are from a spontaneous mutationare from a spontaneous mutation

1 in 3000 live male births1 in 3000 live male births Gene located at Xp21 region of X chromosomeGene located at Xp21 region of X chromosome Gene product is the protein Dystrophni, which Gene product is the protein Dystrophni, which

is a cytoskeletal muscle proteinis a cytoskeletal muscle protein Clinical features of proximal limb weakness Clinical features of proximal limb weakness

occur by the age of 4 and the diseases usually occur by the age of 4 and the diseases usually causes death by 20 years.causes death by 20 years.

Becker’s MD is similar but milder and presents Becker’s MD is similar but milder and presents later.later.

Clinical featuresClinical features

Difficulty running Difficulty running Gower’s sign of proximal leg Gower’s sign of proximal leg

weaknessweakness Pseudohypertrophy of the calvesPseudohypertrophy of the calves Myocardium is affected and a Myocardium is affected and a

cardiomyopathy occurscardiomyopathy occurs Usually disabled by the disease by Usually disabled by the disease by

10 years of age10 years of age

InvestigationsInvestigations

Clinical diagnosis. Very high levels Clinical diagnosis. Very high levels of CK. Muscle biopsy shows of CK. Muscle biopsy shows characteristic changes and characteristic changes and immunochemistry confirm absence immunochemistry confirm absence of dystrophin. EMG shows a of dystrophin. EMG shows a myopathic patternmyopathic pattern

ManagementManagement

No treatmentNo treatment Carrier detection: females with Carrier detection: females with

affected brothers have a 50% chance affected brothers have a 50% chance of carrying the abnormal gene. She of carrying the abnormal gene. She are asymptomatic but have high CK are asymptomatic but have high CK levels, abnormal EMGs and muscle levels, abnormal EMGs and muscle biopsies.biopsies.

Anaesthetic implicationsAnaesthetic implications

1.1. Weak respiratory muscles and Weak respiratory muscles and kyphoscoliosis impair ventilation pre and kyphoscoliosis impair ventilation pre and post oppost op

2.2. Cardiomyopathy and arrhythmias are Cardiomyopathy and arrhythmias are commoncommon

3.3. Delayed gastric emptying and poor bulbar Delayed gastric emptying and poor bulbar function predispose to aspirationfunction predispose to aspiration

4.4. Rhabdomyolysis and an MH-like syndrome Rhabdomyolysis and an MH-like syndrome can follow use of Suxamethonium.can follow use of Suxamethonium.

5.5. Very sensitive to depolarising and non Very sensitive to depolarising and non depolarising muscle relaxants.depolarising muscle relaxants.

Myotonic dystrophyMyotonic dystrophy

Autosomal dominant disease. A triplet Autosomal dominant disease. A triplet repeat disorder.repeat disorder.

1 in 20,0001 in 20,000 Characterised by myotonia = Characterised by myotonia =

incomplete muscle relaxation after incomplete muscle relaxation after exercise.exercise.

Defect in sodium-chloride channels in Defect in sodium-chloride channels in muscle membranemuscle membrane

Onset around 20 to 50 yearsOnset around 20 to 50 years

Clinical features:Clinical features:

MuscleMuscle Progressive distal muscle weaknessProgressive distal muscle weakness Ptosis and bulbar failurePtosis and bulbar failure Weak and wasted facial muscles and SCMWeak and wasted facial muscles and SCM Myotonia Myotonia Cardiomyopathy and conduction defectsCardiomyopathy and conduction defects Central and Obstructive Sleep ApnoeaCentral and Obstructive Sleep Apnoea

Non muscleNon muscle Cataracts, frontal baldness, mild learning Cataracts, frontal baldness, mild learning

difficulties, glucose intolerance, thyroid difficulties, glucose intolerance, thyroid adenomaadenoma

Anaesthetic implicationsAnaesthetic implications

Tolerate surgery very poorlyTolerate surgery very poorly Myotonia can be precipitated by cold, Myotonia can be precipitated by cold,

shivering, mechanical or electrical simulation, shivering, mechanical or electrical simulation, suxamethonium and anticholinesterases suxamethonium and anticholinesterases (neostigmine)(neostigmine)

Increased respiratory complications.Increased respiratory complications. Keep normothermicKeep normothermic Monitor NM functionMonitor NM function Increased sensitivity to thiopentone and Increased sensitivity to thiopentone and

propofol, suxamethonium and non depolarising propofol, suxamethonium and non depolarising muscle relaxantsmuscle relaxants