Transcript Muscle Disorders and General Anaesthetics

Muscle Disorders and
General Anaesthetics
Ben Creagh-Brown, UHL
May 2004
Muscle disease (Myopathy ) can be
divided into
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Myositis – inflammatory disease
Muscular dystrophy – inherited disorder with
progressive weakness
Myotonia - sustained contraction and slow
relaxation
Channelopathies – disorders of ion channels
within skeletal muscle cells
3 main groups to be considered
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Myasthenia Gravis and LEMS
Duchenne’s and Becker’s Muscular Dystrophy
Myotonic dystrophy
Myasthenia Gravis and LEMS
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A 25 year old female presents for thymectomy for
myasthenia gravis
1.
What is myasthenia gravis?
Tell me as much as you know about it
How is it diagnosed? (include EMG)
What is edrophonium?
How does it work?
What dose should be used?
What are the symptoms?
How would you anaesthetise her?
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Description
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Myasthenia Gravis (MG) is an autoimmune condition
in which IgG autoantibodies interact with the
postsynaptic acetylcholine receptors (AChR) at the
nicotinic neuromuscular junction (NMJ).
The AChR antibodies reduce the number of functional
receptors by:
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blocking attachment of ACh molecules
increasing the rate of degeneration of the receptors
complement-induced damage to the NMJ.
On average MG patients have 30% of the normal
number of functional AChR.
Incidence
1 in 10,000 of the population
Age
Two peaks: 20-30 years in women and 60-70 years
in men.
Sex
Twice as common in women
Aetiology and associations
Acquired autoimmune disease of unknown cause.
Can be a result of D-penicillamine treatment for
rheumatoid arthritis.
Associated with other organ-specific autoimmune
diseases
Pathology
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 features
Progressive weakness and fatiguability of
voluntary muscle, particularly ocular, proximal
limb, bulbar and facial muscles. Myocardium
never involved. Fatiguability is weakness
accentuated by exercise and relieved with rest.
Complications
Respiratory failure. Aspiration from bulbar palsy.
Prognosis
Normal or nearly normal lives. Some case of
myasthenia gravis may go into remission
temporarily. In a few cases, the severe weakness
of myasthenia gravis may cause respiratory
failure.
Investigations
Antibodies
Serum AchR antibodies can be found in 90% of
generalised MG, not likely to be found in pure
ocular disease. Pathognomic
Electromyogram
Electromyography (EMG). Compound muscle
action potentials (CMAP) shows that repetitive
stimulation results in progressive decrease in
CMAP = fade. These findings are not specific.
Tensilon test
Edrophonium (tensilon) test. 10mg of this
anticholinesterase is given IV as a bolus (after a 12mg test dose). Improvements in weakness
happen within 30 s and lasts for up to 5 mins. Test
dose is because it can cause bronchoconstriction
and syncope.
Treatments
Anticholinesterase
treatment
To enhance NMJ transmission by delaying
degradation of Ach. Pyridostigmine is the most
commonly used drug. Acts within 30 mins and
lasts for 4 hours. Initially works well but effective
diminishes over months.
Immunosuppression
Immunosuppression with prednisolone or
azathioprine. Start high and taper down
Plasma exchange and
immunoglobulin
Inducing remission of myasthenic crises or pre-op
before thymectomy. Both work within days IV Ig
has a longer effect.
Thymectomy
Thymectomy if thymoma either by sternotomy or
mediastinoscopy. Can do thymectomy for thymic
hyperplasia aiming to induce remission – these
may take a long time.
Pyridostigmine
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Analogue of neostigmine
More effectively absorbed from the gut
With equipotent doses, pyridostigmine has a
slower onset and longer duration of action, and
produces fewer gastrointestinal side effects than
neostigmine
Patients may get the side effects of diarrhoea
and abdominal cramps so they take atropine
0.5mg with each dose
Anaesthetic management
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Avoid drugs that exacerbate MG
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polymyxin antibiotics (such as colistin) block
AChR but are rarely used anyway
Aminoglycosides decrease Ach release and AChR
sensitivity and should be avoided
Procainamide exacerbate weakness
Quinine exacerbate weakness
Beta blockers exacerbate weakness
Pre operative assessment
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Assessment of respiratory function (serial FVC on the ward) and
bulbar weakness (SALT)
Chest physiotherapy
Optimise immunosuppression and anticholinesterase therapy
Consider IV Ig or plasma exchange
Consider ITU bed, prolonged ventilation post op more likely if:
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Stage III or IV disease
Chronic respiratory disease
FVC <2.9l
Long history of disease (>6 years)
Exclude associated thyroid disease or DM
Airway ?RA ?Thymic mass compressing
On day of operation
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Give anticholinesterases or not? Why?
Omit anticholinesterase therapy as this may
prolong action of sux, require increased doses
of non depolarising meuromuscular blocking
drugs
Increased steroids, IV hydrocortisone
Induction and maintenance
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Consider IABP as well as routine monitoring if sternotomy
Continuously monitor NM blockade
Intubate – need to protect the airway. Consider nasotracheal
intubation if planned postop ventilation.
Some anaesthetists avoid IV induction and paralysis but intubate
after deepening with inhalational agents only, MG patients are
more susceptible to the muscle relaxant effect of volatile.
You may require more sux that usual and consequently get a
Phase II block
Conversely they are exquisitely sensitive to non depolarising
neuromuscular blocking drugs (NDNMB) Use 30-40% of the
usual dose of vecuronium or atracurium.
Avoid reversing the NDNMB drugs to avoid the risk of
cholinergic crisis
Post operative
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Majority can be safely extubated and go back to
the ward
HDU may be appropriate
ITU if ventilation required
Good analgesia including opiates.
LEMS
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Lambert-Eaton Myasthenic Syndrome - a rare syndrome occurring in
association with small cell carcinoma of the bronchus.
LEMS results from an autoimmune attack directed against the Voltage Gated
Calcium Channels (VGCC) on the presynaptic motor nerve terminal (in 98%
of those with cancer)
Antibodies have been found in the majority of patients with LEMS.
3% of patients with SSLC.
Clinical features similar to MG but facial and bulbar muscles relatively spared
Distinguishing between the two diseases on EMG: Facilitation (strength
improvement after exercise) is common in LEMS. Facilitation differentiates
the 2 diseases only if it is noted after repeated testing of many separate
muscle groups
They improve with the edrophonium test but not as markedly
Very sensitive to both depolarising and non depolarising drugs
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There are other rare myasthenic syndromes including congenital
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Duchenne’s Muscular Dystrophy
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X linked recessive disorder, A third of cases are from a
spontaneous mutation
1 in 3000 live male births
Gene located at Xp21 region of X chromosome
Gene product is the protein Dystrophni, which is a
cytoskeletal muscle protein
Clinical features of proximal limb weakness occur by
the age of 4 and the diseases usually causes death by 20
years.
Becker’s MD is similar but milder and presents later.
Clinical features
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Difficulty running
Gower’s sign of proximal leg weakness
Pseudohypertrophy of the calves
Myocardium is affected and a cardiomyopathy
occurs
Usually disabled by the disease by 10 years of
age
Investigations
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Clinical diagnosis. Very high levels of CK.
Muscle biopsy shows characteristic changes and
immunochemistry confirm absence of
dystrophin. EMG shows a myopathic pattern
Management
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No treatment
Carrier detection: females with affected brothers
have a 50% chance of carrying the abnormal
gene. She are asymptomatic but have high CK
levels, abnormal EMGs and muscle biopsies.
Anaesthetic implications
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Weak respiratory muscles and kyphoscoliosis
impair ventilation pre and post op
Cardiomyopathy and arrhythmias are common
Delayed gastric emptying and poor bulbar
function predispose to aspiration
Rhabdomyolysis and an MH-like syndrome
can follow use of Suxamethonium.
Very sensitive to depolarising and non
depolarising muscle relaxants.
Myotonic dystrophy
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Autosomal dominant disease. A triplet repeat
disorder.
1 in 20,000
Characterised by myotonia = incomplete muscle
relaxation after exercise.
Defect in sodium-chloride channels in muscle
membrane
Onset around 20 to 50 years
Clinical features:
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Muscle
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Progressive distal muscle weakness
Ptosis and bulbar failure
Weak and wasted facial muscles and SCM
Myotonia
Cardiomyopathy and conduction defects
Central and Obstructive Sleep Apnoea
Non muscle
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Cataracts, frontal baldness, mild learning difficulties, glucose
intolerance, thyroid adenoma
Anaesthetic implications
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Tolerate surgery very poorly
Myotonia can be precipitated by cold, shivering,
mechanical or electrical simulation, suxamethonium and
anticholinesterases (neostigmine)
Increased respiratory complications.
Keep normothermic
Monitor NM function
Increased sensitivity to thiopentone and propofol,
suxamethonium and non depolarising muscle relaxants