The Dept of Anaesthesia & Intensive Care, CUHK thanks

for an unrestricted education grant
BASIC for Nurses, Dubai, April 2015
Airway Management: beyond BASIC, Frankston, April 2015
Intensive Care Nephrology: beyond BASIC, Singapore April 2015
Upcoming BASIC courses

Home Feedback Contents

Myasthenia gravis

Up ADEM Brain abscess Brain death Cerebral oedema Cerebral tumours CVT CVA Coma Cord compression Delirium Encephalitis Guillain Barre syndrome ICU acquired weakness ICH Meningitis Myasthenia gravis Periodic paralysis Nerve lesions SAH Status epilepticus Subdural empyema SjO2 Tick paralysis Transverse myelitis Weakness


Updated Jan 2009 by Charles Gomersall

Epidemiology

- 1/20 000 adults
- females >> males
- peak incidence in 3rd decade in women, in 6th in men
- associated with other auto-immune diseases, particularly other organ-specific auto-immune diseases

Pathophysiology

  • auto-immune
  • antibodies to post-synaptic ACh receptor in 90%. Usually IgG. T
    • 2 populations of receptors: stable (t1/2 12/7) and rapid turnover (t1/2 1/7). ? latter precursors of the former. Rapid response to plasmaphoresis due to rapid regeneration of latter
    • clinical features manifest when skeletal muscle unable to synthesize receptors at a sufficiently high rate to maintain normal neuromuscular function
    • believed that myeloid cells within thymus have ACh receptors on their surface which serve as a source of autoantigen to trigger an immune response
  • other patients may have antibodies to other post-synaptic muscle components such as muscle specific kinase (MuSK)
    • in patients with anti-MuSK antibodies disease tends to primarily affect facial, bulbar, respiratory and neck muscles with relative sparing of limbs
  • 70% of patients have thymic hyperplasia (tend to be younger patients) and 10-15% have thymomas (tend to be elderly)
  • as disease progresses pre-synapatic receptor may become involved (fade of TOF twitch response seen before NDMR given)

Investigations

  • ACh receptor antibodies. NB false positives may occur in: first degree relatives, organ-specific autoimmune disease, thymoma without MG, following penicillamine treatment. Latter will also exacerbate pre-existing MG. Titre of antibody important
  • MuSK antibody titre
  • positive edrophonium test
    • less widely used in recent years due to adverse effects (including severe bradycardia) and subjectivity of testing
    • used to distinguish between cholinergic crisis and myasthenic crisis
    • resuscitation facilities must be available. Atropine 0.6 mg given first or at least drawn up. Give 1 mg edrophonium first followed by a further 4-10 mg 1-2 min later if there is no response. IM neostigmine 1-2 mg may produce a positive response in 5-10% of patients who did not respond to edrophonium
  • EMG shows characteristic changes in 90% of patients with generalised MG and many of those with ocular MG only
  • other useful investigations include:
    • and single-fibre electomyography

Thymectomy

  • early thymectomy advocated in virtually all patients, regardless of severity of disease or presence of a thymoma
  • results in earlier onset of remission, lower mortality and greater delay in appearance of extrathymic recurrences compared with medical treatment
  • pre-operative optimization of neuromuscular function is necessary: use anticholinesterases ± plasmaphoresis
  • in immediate post-operative period anticholinesterase requirements usually reduced to about ¾ of pre-op dose
  • sustained improvement may not be seen for several months

Response to anaesthetic drugs

- response to both depolarizing and non-depolarizing relaxants unpredictable, depending to some degree on severity and duration of disease
- when in remission response to relaxants is normal
- small doses of both atracurium and vecuronium have been used safely
- continuation of anti-cholinesterases in pre-operative period controversial

  • if treatment stopped before surgery patient often very weak on presentation in anaesthetic room and may be distressed by this. Need for relaxants much reduced but by end of surgery patient is even more weak and large doses of anticholinesterase may then be indicated with increased risk of a cholinergic crisis
  • if drugs continued larger doses of NDMRs will be required

- ? post-op IPPV will probably be necessary for patients who have had disease > 6 yrs or who have co-existing respiratory disease with a VC < 2.9 l or who take more than 750 mg pyridostigmine daily. Some advocate stopping anticholinesterases temporarily in those who require mechanical ventilation to reduce respiratory secretions
- epidural anaesthesia is said to exacerbate condition but has been used succesfully for LSCS although dose reduction necessary to prevent excessive motor block

Myasthenic crisis

  • Predominant problem is neuromuscular respiratory failure
  • Incidence increases markedly with age
  • Distinguished from cholinergic crisis by the presence (in cholinergic crisis) of:
    • abdominal cramps
    • excessive secretions
    • sweating
    • bradycardia

Precipitating factors

  • intercurrent infection
  • pregnancy
  • drugs:
    • antibiotics, eg aminoglycosides, polymyxins, tetracycline
    • anti-arrhythmics, eg quinidine, quinine, procainamide
    • local anaesthetics, eg procaine, lignocaine
    • muscle relaxants
    • analgesics, eg morphine, pethidine

Complications

  • aspiration due to bulbar involvement
    • check cough and swallowing
  • nosocomial pneumonia
  • atelectasis
  • acute respiratory failure
  • cardiac arrest

Investigations and monitoring

  • ± edrophonium test after stabilization to distinguish between myasthenic and cholinergic crisis
  • check VC and max insp force regularly. Best method of monitoring
  • deterioration of ABG may occur late
  • avoid hypokalaemia, hypocalcaemia, hypermagnesaemia as all exacerbate weakness
  • if adjustment of anticholinesterase and aggressive treatment of intercurrent illness does not result in rapid improvement high dose steroids and plasma exchange should be started simultaneously

Management

  • Intubate when VC falls below 15 ml/kg
  • Aims of ventilation
    • Rest patient
    • Prevent collapse and atelectasis
  • Anticholinesterase

    • role in myasthenic crisis unclear. Limited data call into question the usefulness of these drugs in myasthenic crisis
    • pyridostigmine PO 60 mg 4-6 hrly. Can be increased to a maximum of 480 mg/day. Onset of action 30-60 min after oral dose
    • pyridostigmine IVI in myasthenic crisis (0.5-4 mg/hr titrated against repeated edrophonium tests) Has advantage of avoiding excessive troughs and cholinergic side effects in association with peaks
    • neostigmine IV 15 mg 3-4 hrly up to 150 mg/day is an alternative
    • complications: bronchorrhoea, bradycardia, diarrhoea, cholinergic crisis

    Immunotherapy

    • steroids effective in 70%. Start with high dose (eg prednisolone 100mg daily) and then reduce gradually. Transient exacerbation on starting steroids very common and therefore usually used in combination with other therapies (eg IV Ig or plasma exchange). Older patients are more likely to respond but an average of 4 months treatment is required to achieve clinical stability. Majority require indefinite treatment
    • azathioprine, cyclophosphamide. Effective adjuncts to steroids, especially in patients with thymoma. Overall 80% are helped but improvement may take months. A few patients achieve complete remission
    • plasma exchange produces short-term improvement. Mainly used for myasthenic crisis and to improve severely affected patients before thymectomy. Typically 5 exchanges of 3-4 l performed over 2 weeks. Improvement usually occurs within days but last only weeks
    • IV gamma globulin
      • alternative to plasma exchange in patients with myasthenic crisis or prior to surgery and/or thymectomy
        • 1-2 g/kg in 2-5 divided doses
      • as maintenance therapy for moderate to severe MG with other treatments have been ineffective or caused intolerable side effects
        • 0.4-1/kg 4-6 weekly

Prognosis & course

  • ~5% mortality.Usually due to comorbid conditions
  • usually last weeks, occasionally months

Myasthenic syndrome

- = Eaton-Lambert syndrome
- paraneoplastic
- pre-synaptic disorder
- ? antibody to presynaptic membrane resulting in decreased acetylcholine release
- associated with increased sensitivity to both depolarizing and non-depolarizing muscle relaxants. May even experience significant weakness after single dose of aminoglycoside
- anticholinseterases not helpful
- patients may experience transient increase in muscle strength on exercise, usually followed by a prolonged period of fatigue
- EMG: marked post-tetanic facilitation and steady growth of potential on tetanic stimulation
- removal of tumour may result in a striking, although temporary, improvement in clinical condition

Further reading

Janjua N, Mayer SA. Critical care of myasthenic crisis. In Vincent J-L (ed) Yearbook of Intensive Care and Emergency Medicine 2003. Springer-Verlag, Berlin, pp765-775

Jani-Acsadi A, Lisak RP. Myasthenic crisis: guidelines for prevention and treatment. J Neurol Sci, 2007; 261:127-33

Jurisdictional Blood Committee, for and on behalf of the Health Minister's Conference. Criteria for the Clinical Use of Intravenous Immunoglobulin in Australia. Canberra: Commonwealth of Australia; 2007


 ©Charles Gomersall Jan 2009

©Charles Gomersall, February, 2015 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
Copyright policy    Contributors