1. Anaesthesia in myasthenia Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics, PhD (physio) Mahatma Gandhi Medical college and research institute, puducherry India

2. What is myasthenia gravis MG is an autoimmune disorder – circulating antibodies to nicotinic acetylcholine receptors at the neuromuscular junction antibodies reduce the numbers of receptors Symptoms if only 30% receptors are present re Up to 25% of patients have a concurrent thymoma, About 10% have evidence for other autoimmune diseases

3. ors reduced to 30% of normal

4. Clinical features muscle weakness -an overall fatigability increases with exertion over the course of the day. 14:100,000 age 10 and 40. (bimodal ) Females are more frequently affected diplopia and ptosis resulting from weakness of the ocular muscles. slowly spread to bulbar muscles, which may lead to aspiration and respiratory failure, and later affect the proximal extremities

5. Osserman and Genkins class I (ocular muscles only); class II (eye symptoms plus mild generalize weakness); class III (eye plus moderate weakness); class IV (eye plus severe weakness); class V (intubation, ventilation)

6. How to diagnose ? blood tests for antibodies; electromyographic recordings; electrophysiologic evaluation is often performed and shows a classic decrement in the compound muscle action potential after repetitive nerve stimulation.

7. cholinesterase inhibitor test (edrophonium test); Tensilon test (administration of an anticholinesterase, e.g., edrophonium). Improvement is usually seen within 5 minutes after administration of the drug and lasts for about 10 minutes Imaging (to identify thymoma).

8. Drugs aggravate Neuromuscular weakness Penicillamine Nondepolarizing muscle relaxants Aminoglycosides Procainamide

9. Some other DD s of myasthenia Graves' disease Eaton lambert syndrome Cranial nerve palsies Congenital myasthenic syndromes

10. Other autoimmune diseases coexisting hyperthyroidism is present in approximately 10% of patients with myasthenia gravis. Rheumatoid arthritis, SLE, and pernicious anemia occur more commonly in MG

11. Treatment Two problems I. muscle weakness Cholinesterase inhibitors (neostigmine, Pyridostigmine (maximal dose )120 mg every 3 hours)

12. Problem 2. immunosupression corticosteroids and immunosuppressive drugs (cyclosporine, azathioprine) Plasmapheresis-(four to eight treatments over 2 weeks thymectomy is performed if general symptoms are present

13. Anaesthetic challenges Preop evaluation preoperative interview that they may be intubated and ventilated when they awaken All routine investigations ECG -- Cardiac arrhythmias and myocarditis

14. Preop preparation pyridostigmine ↓ Bad response ↓ good response Young old ↓ ↓ Steroids steroids + azathioprine ↓ ↓ Imp. Not imp imp.→taper steroids →thy ↓ ↓ Thy add plasma

15. Preop preparation Only plasmapheresis

16. Preop Lung function testing Respiratory and bulbar functions should be carefully evaluated during the preoperative evaluation Preop neurologist evaluation Preoperative plasmapheresis

17. Post op ventilation ??  Four Factors  disease duration of longer than 6 years,  chronic obstructive pulmonary disease(COPD) unrelated to myasthenia gravis, a daily dose of pyridostigmine higher than 750 mg, and a vital capacity less than 2.9 L.

18. Premed Anticholinesterase to continue ?? Small dose benzodiazepine Anticholinergics

19. Anaesthetics-Nondepolarizing Neuromuscular Blockers Long acting NDNMB (pancuronium, pipecuronium, doxacuronium) :avoided Intermediate and short acting: used with careful monitoring..

20. Depolarizers nondepolarizers

21. Succinylcholine resistance to depolarizing agents.( ED 95 : 2.6 times of control) because of the decreased number of functional acetylcholine receptors more likely to develop phase II block decrease in cholinesterase activity achieved by anticholinesterase treatment

22. So regarding relaxants NDP s more sensitive Depolarizers more resistant

23. Inhaled Anaesthetics Isoflurane, enflurane: decrease TOF responses Sevoflurane at 2.5% depresses EMG responses effects of desflurane in MG ??

24. Intravenous Anaesthetic Agents Propofol √ -- no effect on NMJ Etomidate, althesin and ketamine : Reports of uneventful anesthesia. Opioids –d–do not appear to depress NM transmission in MG muscle. –C–Central respiratory depression may be a problem

25. Anaesthesia -1 IV induction + inh. Drugs + intubation Maintain on N2O,O2, Inh. Agent No NonDepolarizers Extubate without reversal

26. Anaesthesia - 2 Propofol Scoline N2O,O2, Inh. Agent Nondepolarizers (10% dose with NMJ monitor) unsuccessful extubation, longer postoperative mechanical ventilation and hospital stay Suggamadex or post op ventilation

27. Regional Anesthesia Ester anesthetics, metabolized by cholinesterase, may present particular problems in patients taking anticholinesterases. Use reduced doses of amide (lidocaine, bupivacaine) to avoid high blood levels. Remember drugs and coexisting diseases

28. Anaesthesia 3, 4 TIVA for the management of myasthenics has been reported. Local anaesthesia is successful

29. Postoperative considerations Weakness Pain (local,epidural opioids ) Myasthenic crisis Cholinergic crisis Resume the anticholinergic therapy as soon as possible after surgery. The postop requirements may be different from the routine preoperative dose and careful titration because the IV dose is only about 1/30 to 1/120

30. Post op problems Nerve stimulator - bulbar Vs limb muscles Inspiratory force of > - 25 cm is OK Trans sternal thymectomy – 50 % req. ventilation Trans cervical thymectomy OR video-assisted thorascopic (VATS)– less post op ventilation,remission more ?? Early thymectomy better !!

31. Your icu ready

32. Myasthenic crisis Myasthenic crisis is a life-threatening condition, which is defined as weakness from acquired myasthenia gravis (MG) that is severe enough to necessitate intubation

33. precipitants infection. Surgery Pregnancy, certain antibiotics (aminoglycosides, erythromycin and azithromycin), cardiac drugs (beta-blockers, procainamide, and quinidine), and magnesium. TREAT VIGOROUS WITH POSSIBLE OPTIONS

34. Cholinergic crisis excess of cholinesterase inhibitors (ie, neostigmine, pyridostigmine, physostigmine) resembles organophosphate poisoning. excessive ACh stimulation of striated muscle at nicotinic junctions produces flaccid muscle paralysis that is clinically indistinguishable from weakness due to MG.

35. Cholinergic crisis Miosis and the SLUDGE syndrome (ie, salivation, lacrimation, urinary incontinence, diarrhea, GI upset and hypermotility, emesis) also may mark cholinergic crisis. Despite muscle weakness, deep tendon reflexes are preserved.

36. Cholinergic crisis When muscarinic effects are obvious, diagnosis is easily made. Antimuscarinics and respiratory support are given EDROPHONIUM TEST WILL DIFFERENTIATE BOTH CRISES

37. Myasthenia and pregnancy Exacerbations of myasthenia must be anticipated during pregnancy Epidural analgesia and anaesthesia can be used for labour and delivery Muscle relaxation induced by regional anaesthesia may compound the weakness caused by myasthenia.

38. Myasthenic syndrome Acq. Disorder Small cell ca of lungs IgG antibodies to pre synaptic voltage dep. Calcium channels Abn. Vesicular release Exercise improves Diaminopyridine improves Sensitive to both DPs and NDPs anticholinesterase agent - not dependable

39. SUMMARY Preop bulbar? Anticholinestrase, plasmapheresis, premed atropine GA with propofol, inh. agents,no NDPs Post op ventilation Or GA, relaxants, suggamadex, ventilation Other surgeries – possible RA, LA Post op epidural opioids, muscle weakness

40. Thank you all