Neuromuscular disease and anaesthesia
Dr Nicholas Hirsch, Consultant Anaesthetist
The National Hospital for Neurology & Neurosurgery, Queen Square
The two most commonly encountered neuromuscular diseases are
myasthenia gravis and the Lambert Eaton myasthenic syndrome. Both have
important implications for the anaesthetist.
Myasthenia gravis (MG)
MG is an autoimmune disease in which IgG antibodies are directed towards
the postsynaptic acetylcholine receptors (AchR) of the neuromuscular
junction. Accelerated degradation and blocking of the AchR results in
decreased receptor density which leads to the cardinal feature of MG –
weakness and fatiguability of voluntary muscle. The thymus gland, which is
abnormal in 85% of MG patients (either hyperplasia or thymoma), appears to
be instrumental in the production of the antibodies.
Epidemiology: prevalence of MG is approximately 100 per 100 000 population
with incidence of 2-4 per 100 000 per annum. More common in young women
and older men.
Clinical features: ocular symptoms (ptosis and diplopia) occur in 90%, limb
and trunk weakness in 70%, bulbar weakness in 80%. Respiratory muscle
weakness more common than suspected. Neurological defect is confined to
the motor system and reflexes are normal. Symptoms are classically worse
after a period of exercise (eg in the evening).
Classification of MG (Osserman): grade I – only eyes affected, grade IIa –
mild generalised MG responding well to therapy, grade IIb – moderate
generalised MG responding less well, grade III – severe generalised disease,
grade IV – myasthenic crisis requiring mechanical ventilation.
Associated autoimmune conditions include: thyroid abnormalities (15%),
systemic lupus erythematosis, rheumatoid disease, ulcerative colitis,
pernicious anaemia, vitiligo and pemphigus.
Diagnosis of MG: depends on careful history and examination,
pharmacological tests, electromyography (EMG) and detection of the
antiAchR antibody.
Pharmacological tests: main test is the Tensilon (edrophonium) test. Up to
10mg of the anticholinesterase is given iv. Expect improvement in muscle
power within 30s and lasting 5 minutes. False negatives common.
EMG testing: shows similar effects of small dose of non depolarising relaxant
on normal subjects ie reduced compound muscle action potentials (CMAP) to
single supramaximal twitch and decrement (fade) of > 10% on tetanic
stimulation. Single fibre EMG shows ‘jitter’. EMG findings not exclusive to MG.
Detection of antiAchR antibodies: positive in 85% of MG patients and
pathagnomic.
Treatment of MG: consists of anticholinesterase therapy, immunosuppression
and thymectomy. Plasma exchange and intravenous immunoglobulin (IvIg)
used to produce short-term remission.
Anticholinesterases: pyridostigmine (mestinon) most commonly used. Acts
within 30 mins, peak effect at 2 h and clinical half-life of 4 h. Overdose may
cause cholinergic crisis. Effects of anticholinesterases dramatic initially but
tachyphylaxis occurs within a few months in most patients.
Immunosuppression: corticosteroids are the mainstay of treatment. Aim for
alternate day regimen. Patients often deteriorate 7-10 days after starting
treatment – should be initiated in hospital if severe MG. Azathiaprine is often
used in conjunction with steroids.
Thymectomy: indicated in most patients with MG in order to promote
remission or to prevent local spread of thymoma. Performed either via median
sternotomy or transcervical route. May take up to 24 months to fully realise
benefits.
Plasma exchange (PE) and IvIg: used to treat severe myasthenic weakness
or crisis.
Anaesthesia and myasthenia gravis
Obviously depends on the severity of MG and the procedure being
considered. Often MG patients present for elective thymectomy.
Preoperative considerations:
Patients should be admitted 24-48h before surgery to allow detailed
assessment of respiratory muscle and bulbar function and review of
anticholinesterase and corticosteroid therapy. Respiratory reserve most
reproducibly monitored by serial forced vital capacity (FVC) measurement.
Preoperative factors associated with need for prolonged postoperative IPPV
include: FVC < 2.9l, history of MG > 6 years, co-existing lung disease and
grades III and IV MG. Consider preoperative PE or IvIg.
Premedication: sedative premed often avoided if respiratory function marginal
but anticholinergic useful. Anticholinesterase medication withheld on morning
of surgery as patients often do not require it immediately postoperatively and
they prolong the effect of suxamethonium and possibly antagonise non depolarising neuromuscular blockers (NDNMD). Hydrocortisone ‘cover’
should be given to those on long-term corticosteroid therapy.
Induction of anaesthesia: following introduction of routine monitoring
(including that of neuromuscular monitoring) induce with thiopentone or
propofol. Tracheal intubation usually achieved by deepening anaesthesia with
inhalational agents. Patients with MG are more sensitive to the NMJ blocking
effects of these agents. Use a nasotracheal tube if expecting a period of
prolonged postoperative ventilation.
Response to neuromuscular blocking drugs: due to the reduced number of
AchR, patients with MG may be relatively resistant to normal doses of
depolarising relaxants. Higher doses may result in a phase II (nondepolarising) block. In contrast, MG patients show extreme sensitivity to
NDNMB drugs and doses must be reduced. Sensitivity varies (eg require 10%
of a dose of curare, but 30-40% of a dose of vecuronium or atracurium).
The latter drugs are favoured, as they do not require the use of
anticholinesterase drugs for reversal. These theoretically increase the risk of a
cholinergic crisis postoperatively.
Postoperative management: patients may have their tracheas extubated if
they fulfil the usual criteria. However, those undergoing median sternotomy
benefit from a short period of postoperative IPPV that allows adequate
analgesia to be administered. They should be nursed in a high dependency
area. Anticholinesterase drugs are restarted at a reduced dose in the
immediate postoperative period.
Lambert Eaton myasthenic syndrome (LEMS)
LEMS is an autoimmune disorder of the neuromuscular junction in which IgG
autoantibodies are directed towards the voltage gated calcium channels of the
presynaptic terminal of the NMJ. Because release of acetylcholine (Ach)
depends on functioning calcium channels, the condition results in a decrease
in the number of quanta released by each nerve impulse. This results in
weakness of voluntary muscle. However, unlike MG, muscle power increases
with exercise as this results in increased release of Ach presynaptically.
Clinical features: 60% of patients with LEMS have an underlying malignancy
(usually small cell lung cancer). Others have autoimmune diseases such as
polyarteritis nodosa. Most patients present with muscle weakness, dry mouth,
erectile dysfunction and constipation. Unlike MG, tendon reflexes are
depressed and muscle pain is common.
Diagnosis: depends mainly on history, examination, EMG studies and
detection of the calcium channel antibodies.
EMG: shows reduced CMAPs on single twitch but on tetanic stimulation
shows an increment of > 100% on tetanic stimulation (cf MG which shows a
decrement). Like MG, single fibre stimulation shows ‘jitter’.
Treatment: this is directed at enhancing neuromuscular transmission by
increasing Ach release presynaptically, immunosuppression and surgery.
Improving neuromuscular transmission: 3,4 diaminopyridine increases release
of Ach presynaptically by reducing the number of voltage gated potassium
channels, thereby prolonging the action potential and increasing quantal
release.
Immunosuppression: corticosteroids, azathiaprine and cyclosporin have all
been used successfully.
Surgery: resection of bronchial carcinoma may improve muscle power.
Plasma exchange and IvIg may be effective short-term treatments.
Anaesthesia and LEMS
Preoperative considerations are similar to that for the MG patient. However,
patients with LEMS are extremely sensitive to both depolarising and nondepolarising neuromuscular blocking drugs and these drugs should be
avoided if possible. Although the literature is sparse, it has been suggested
that 10% of the normal dose of NDNMB drug should be used. Careful
monitoring of neuromuscular function is essential. Furthermore,
anticholinesterase reversal of NDNMB may be ineffective.
Further reading:
Drachman DB. Myasthenia gravis. N Engl J Med 1994;330:1797-1810.
Baraka A. Anaesthesia and myasthenia gravis. Can J Anaesth 1992;39:476486.
Newsom-Davis J. Lang B. The Lambert-Eaton myasthenic syndrome. In:
Myasthenia gravis and myasthenic disorders. Ed. Engel AG. Oxford: Oxford
University Press; 1999:205-228.