55. Myasthenia Gravis Flashcards
What is myasthenia gravis?
This is a rare condition characterised by fatigable weakness classically
affecting the ocular, bulbar and proximal limb muscles.
There is destruction of the acetylcholine receptor protein at the
(largely post-junctional)
neuromuscular junction,
resulting in the failure of neuromuscular transmission.
Serum acetylcholine receptor antibodies (polyclonal IgG) are
present in 90% of generalised cases.
Epidemiology / Causes
It is twice as common in females,
is associated with thymoma in 10%–15% of cases
and may be associated with other autoimmune conditions,
e.g. thyrotoxicosis,
rheumatoid arthritis,
pernicious anaemia and SLE.
What is myasthenic syndrome?
This is a paraneoplastic syndrome also known as Eaton–Lambert syndrome
(ELS) characterised by proximal muscle weakness that typically affects the
lower extremities. It is most commonly associated with small-cell carcinoma of
the lung
Can you compare and contrast the two conditions?
- At a molecular level, Eaton–Lambert syndrome results
from a pre-junctional defect in the quantal release of acetylcholine,
which may be due to antibodies directed against calcium channels.
Myasthenia gravis is due to a post-junctional defect as already described
- Clinically, Eaton–Lambert syndrome more commonly affects the lower
limbs. It can also produce autonomic effects (hypotension, gastroparesis or
urinary retention). - Exercise causes improvement in the weakness with Eaton–Lambert
syndrome (‘second wind phenomenon’),
but worsening with myasthenia gravis.
This can be easily demonstrated electrophysiologically
(incrementing response as opposed to decrementing).
- Anticholinesterases do not cause an improvement with Eaton–Lambert
syndrome. Instead, guanidine hydrochloride and 4-aminopyridine often
help by enhancing Ach release by acting on calcium and potassium channels. - Response to neuromuscular blockers. ELS patients are sensitive to both
depolarizing and non-depolarizing muscle relaxants.
Myasthenia gravis patients are resistant to depolarizing muscle relaxants
What problems does a patient with myasthenia gravis pose for the
anaesthetist?
Some form of categorizing this question is worth learning.
The problems of anaesthetizing a myasthenic patient breakdown into:
The problems of. . ..
- Altered response to drugs, esp. muscle relaxants.
- The type of surgery being performed.
- Severity of disease.
- Co-existent medical (auto-immune) disease.
- Intercurrent medication – steroids, etc.
- Exacerbation of disease.
- Post-op respiratory failure.
Altered response to drugs, especially muscle relaxants.
Altered response to drugs, especially muscle relaxants.
The response to suxamethonium is unpredictable.
Relative resistance (ED95 reported as 2.6 times normal),
prolongation or a phase II block may be seen.
Opioids or barbiturates may produce profound respiratory depression.
Patients are often extremely sensitive to non-depolarising relaxants.
Either avoid (patients can often be intubated with volatile alone)
or use at about 1/10 of the usual dose.
However, atracurium has been used without problems
because of its rapid metabolism.
A nerve stimulator must be used.
The type of surgery being performed.
The type of surgery being performed.
With a thymectomy there is a risk of damage to the SVC
and a risk of pneumothorax.
Venous access in the lower limbs may be prudent.
After trans-sternal thymectomy 50% of patients
require post-operative ventilation
Severity of disease:
Severity of disease:
Respiratory or bulbar muscle involvement?
Increased risk of aspiration
Arterial blood gases/CXR/PFTs will be needed to assess respiratory embarrassment
Co-existent auto-immune disease
Co-existent auto-immune disease
Current treatment may include
steroids, azathioprine, cyclophosphamide, cyclosporin and anticholinesterases
(typically pyridostigmine which lasts about 3–4 hours).
Medical treatment should be optimised.
This may include plasmapheresis.
There is debate about whether to reduce or stop anticholinergics before surgery.
Patients are better off being slightly myasthenic rather than cholinergic.
Anticholinesterases may cause:
Increased vagal reflexes (? pre-medicate with atropine)
The possibility of disrupting bowel anastomosis.
Prolonged action of ester-type local anaesthetics and suxamethonium
(inhibition of plasma cholinesterase).
Exacerbation of the disease
Exacerbation of the disease may be caused by
surgery, stress, infection,
aminoglycosides, hypokalaemia and pregnancy.
Post-operative respiratory failure.
Post-operative respiratory failure.
Increased risk with: Disease duration >6 years
Co-existing pulmonary disease
Vital capacity <40 ml/kg
Pyridostigmine dose >750 mg/day
Poor bulbar function.
Apart from needing surgery, how else may you be asked to help with the
management of a myasthenic patient?
Apart from needing surgery, how else may you be asked to help with the
management of a myasthenic patient?
Intensive care management
Performance of an edrophonium (‘Tensilon’) test -distinguishing a
myasthenic crisis from a cholinergic crisis.
There is a risk of bradycardia and bronchoconstriction
What is the difference between a myasthenic crisis and
a cholinergic crisis?
A cholinergic crisis is due to excessive administration of anticholinesterases
and causes increased weakness with pronounced muscarinic effects:
Bradycardia
Salivation
Sweating
Small pupils
Lacrimation
Abdominal pain
Diarrhoea
Edrophonium will exacerbate the weakness.
A myasthenic crisi
A myasthenic crisis is due to under-treatment with anticholinesterases.
Weakness will improve after administration of edrophonium.
