Myasthenia gravis

myaesthenia gravis and anaesthetic implications

1. MYASTHENIA GRAVIS- anaesthetic concerns Dr.Malaka Munasinghe Registrar in Anaesthesia 2015.12.02

2. Outline Introduction Epidemiology Pathophysiology Classification Clinical features Differential Diagnosis Treatement Anaesthetic considerations

3. History Myasthenia (Greek – muscle illness) Gravis (Latin – “grave or serious”) First description in the 17 th century Sir Thomas Willis “ a woman who spoke freely and readily enough for a while, but after a long period of speech was not able to speak a word for one or two hours”

4. Myasthenia Gravis Chronic autoimmune condition Autoantibodies –NMJ post junctional Ach receptors Skeletal muscle weakeness and fatigability

5. Epidemiology Incidence 2-4 per 100,000 per year Prevalence 100 per 100,000 Young women(20-30) and Older men(60-70)

6. Pathophysiology Neuromuscular junction

7. Anti-AChR Abs T T T T B Plasma cell APC Nerve Terminal Postsynaptic membrane AChR MuSK Rapsyn AChase ACh Voltage-gated Na + channel Voltage-gated Ca + channel Ca ++ Ca ++ AChR MuSK

8. Autoantibodies Ach receptor antibody( AchR )- IgG ( Positive in 85% of patients) Muscle specific tyrosine kinase antibody ( MuSK )

9. Anti Ach antibodies Reduce the number of functional receptors Blockade of Ach molecule binding to receptor Increase rate of Ach receptor degredation Complement induced damage to NMJ

10. Thymus and Myasthenia Abnormal in 85% of patients -85% Hyperplasia -15% Thymoma Myoid cells in Thymus express Ach Receptors T and B cells in Thymus get sensitized produce Antibodies

11. Osserman’s classification Type I Ocular signs and symptoms only 11A Generalized mild muscle weakeness responding well to therapy IIB Generalized moderate muscle weakeness responding less well to therapy III acute fulmination presentation and/or respiratory dysfunction IV Myasthenic crisis requiring arteficial ventilation

12. Presentation Fatigability and weakeness Diplopia / Ptosis Disabled chewing Dysphagia Dysphonia / dysarthria /Nasal speech muscle weakeness - Neck - Limb girdle - Respiratory No AUTONOMIC features No SENSORY features 15% Of patients- extraocular muscle involvement only

13. Ptosis

14. D/D Neuromuscular junction diorders - Lambert-Eaton syndrome - Botulism - Acquired Neuromyotonia - Congenital myasthenia - Drug induced myasthenia gravis Metabolic and toxic myopathies Brain stem diseases( ischaemic /inflammatory/ neoplastic )

15. Diagnosis History Examination( Absence of autonomic and sensory fx ) Ix - Serological ( Autoantibodies ) - Electrophysiological ( Decremental motor response to repetitive stimulation of motor nerves) Pharmacological ( Tensilon test) Imaging (CT/MRI chest+neck )

16. IV 10 mg Edrophonium injected-after 30 seconds Improved muscle power for up to 5 minutes Tensilon Test Before After

17. Associated conditions Thyroid disorders(Hypo/hyper) Rheumatoid arthritis Pernicious anaemia SLE Sarcoidosis Polymyositis Ulcerative colitis Sjogren’s disease

18. Treatement Anticholinergic drugs Pyridostigmine / Neostigmine Immune-directed treatments Short-term Plasmapheresis , IV Immunoglobulin Long-term - Corticosteroids - Immunosuppressive drugs( Azathioprine /Cyclosporine) - Thymectomy ( 25% complete remission)

19. Treatement Pyridostigmine Onset 15-30 min Peak effect 2h Duration 4hrs Dose 30mg tds – 90 mg 6hrly CHOLINERGIC CRISIS

20. Prednisolone Low dose 10-20mg/d- increment of 5mg every 3 rd day up to 60mg/d Gradual tailing off to a aminimum EOD dose

21. Azathioprine -Dose 1-2mg/kg/d S/E -Bone marrow suppression/Liver toxicity/Idiosyncratic fly like illness Cyclosporine Dose 5mg/kg/d S/E Nephrotoxicity /Hypertension

22. IV immunoglobulin Indications Severe myasthenia gravis myasthenic crisis Intractable myasthenia Preop and post op period DOSE-400mg/kg for 5days Plasmapheresis - Quick onset - Same efficacy

23. Thymectomy For patients of 15-60 years Total excision needed Indications - Thymoma - Thymic hyperplasia - Myasthenia gravis

24. Drugs exacerbating MG Antibiotics- Macrolides / aminoglycosides /tetracycline/ Chloroquine Antidysrhythmic agents- Beta-blockers/calcium channel blockers/ lidocaine / quinidine / procainamide Misc Lithium/muscle relaxants/ levothyroxine /ACTH

25. Anaesthetic considerations Respiratory reserves Optimization - medication/ ntrition /chest infection Premedication - Depressants/ Anticholinergics Steroid cover Mode of anaesthesia Prediction of need of post op ventilation

26. Mode of anaesthesia Regional and local anaesthesia preferred GA Monitoring( AAGBI+NM Monitoring+IABP ) Intubation under inhalational induction Intubation with relaxants- DMR-Increased dose - NDMR- Reduced dose Reversal not usually needed( risk of Cholinergic crisis)

27. Post operative management Confirm respiratory and bulbar muscle power before extubation Identify patients who need post op ventilation Duration of MG> 6 years (most influential) 12points A history of chronic respiratory disease which is not directly due to MG 10 points A dose of pyridostigmine >750mg/d, 48 hrs before Sx 8 points 4. A preop vital capacity<2.9l 4 points Total score>10-need post op ventilation

28. Myasthenic crisis Exacerbation of myasthenia leading to paralysis of respiratory muscles requiring urgent repiratory support Poor cough RR VC<30ml/kg Increased generalized weakeness Progressive bulbar(speech/swallowing) weakeness

29. Precipitants - Infection - Surgery Pregnancy and child birth Inadequate Rx Initial high dose steroid therapy Drugs

30. Cholinergic crisis Over treatement with anticholinergics Flaccid muscle weakeness Mieosis SLUDGE syndrome Salivation Lacrimation Urinary incontinence Diarrhoea GI upset Emesis

31. Mx of Cholinergic crisis Intubation and ventilation IV Immunoglobulin 400mg/kg/d for 5/365 Plasmapheresis Immnomdulation Prednisolone 60-8-mg/d Azathioprine /cyclosporine Plan weaning from ventilation

32. Myasthenia and Pregnancy Remissions/exacerbations/no change Glucocorticoids / Azathioprine /cyclosporine- SAFE Magnesium/ CCB/Beta blockers to be avoided in Hypertensive diseases 2 nd satge of labour needs assistance Anticholiesterases should be administered IV during labour

33. Questions * 1996 August LEQ -How would you manage a patient with Myasthenia Gravis for elective abdominal surgery? *2007 August LEQ - Discuss the anaesthetic management of a 30 year old female with myasthenia gravis presenting for a trans- sternal thymectomy *2009 August SAQ outline the main characteristic features of Myasthenic syndrome - How and why do they differ from those seen in Myasthenia Gravis?

34. FRCA 2007 What are the clinical features of acquired myasthenia gravis? What tests are available to confirm the diagnosis? What are the important aspects of a patient with generalised myashenia gravis presenting for laparoscopic cholecystectomy ?

35. Thank you!