ANAESTHESIA CONCERNS FOR THYMECTOMY IN MYASTHENIA GRAVIS PTS

1. ANAESTHESIACONCERNS FOR THYMECTOMY INMYASTHENIA GRAVIS PTS Moderated by-Dr. Anil Sharma Presented by- Dr. NainaChandnani

2. MYASTHENIA GRAVIS • Myasthenia gravis (MG) is an autoimmune disorder of synaptic transmission caused by antibodies against nACHRs • Characterized by weakness and fatigability of skeletal muscles . MYASTHENIC NMJ NORMAL NMJ

3. PATHOPHYSIOLOGY • Decrease in no. of available AChRs at the postsynaptic muscle membrane. • Postsynaptic folds are flattened, or "simplified." • So, decreased efficiency of neuromuscular transmission. • Therefore, although ACh is released normally, it produces small end-plate potentials that may fail to trigger muscle action potentials weakness of muscle contraction

4. ETIOLOGY • Autoimmune disorder due to antibodies against α-subunit of nicotinic acetylcholine receptors (nAChRs ) • Antibodies damage and reduce receptors by • cross linking & rapid endocytosis of antibodies to receptors • focal membrane lysis by complement fixation • blockade of the active site of the AChR • Immune response to muscle-specific kinase (MuSK) – primarily in younger pts. • Thymus is abnormal in ~75% of patients • 10% of patients have thymictumors (thymomas)

5. PREVALENCE • 0.5 to 14.2 in 1,00,000 population • Peaks of incidence occur in women in their twenties and thirties (incidence is one in 2-5lakh) • Men in their sixties to eighties. • Overall, women are affected more frequently than men, in a ratio of ~3:2

6. CLINICAL FEATURESSYMPTOMS • Hallmarkskeletal muscle weakness • Fatigue by repetitive use - recovery by rest • Skeletal muscles innervated by cranial nerves are especially vulnerable. • Facial weakness, nasal speech • Weakness in chewing, weakness of palate & tongue, difficulty in swallowing can cause nasal regurgitation or aspiration of liquids or food • Drooping of eyelids, double vision • Limb muscle weakness- waddling gait

7. Blepharoptosis of the left eye. • Myocarditis , AF , Heart block , takotsubocardiomyopathy and sympathetic hyperactivity have been described.

8. SIGNS • Ptosis, diplopia, dysarthria • Limb msl weakness - proximal & asymmetrical • Deep tendon reflexes preserved • If weakness remains restricted to the extraocular muscles for 3 years, it is likely that it will not become generalized, and these patients are said to have ocular MG. • Severe respiratory msl weakness which requires assistance pt. said to be in crisis

9. CLASSIFICATION(Osserman)* • Signs & symptoms limited to extra-ocular msls (20%) IIA. Mild generalized symptoms (30%) IIB. Moderate generalized symptoms with some bulbar symptoms (20%) • Acute severe rapidly progressive with severe bulbar involvement (11%) • Late, severe cases with marked bulbar symptoms & severe generalized weakness (9%) *Osserman KE.Grune and Stratton, 1958, New York

10. Congenital Myasthenic Syndromes • Heterogeneous group of disorders of the neuromuscular junction • Not autoimmune but are due to genetic mutations • Clinical features similar to autoimmune MG • Suspected when symptoms of myasthenia begin in infancy or childhood and AChR antibody tests are consistently negative

11. Transient Neonatal Myasthenia Gravis (TNMG) • Seen in nenates of mother with myasthenia gravis • Antibodies pass to the infant through placenta • Symptoms start in the first two days and disappear within few weeks after birth • Poor suckling, generalized hypotonia, weak cry, respiratory difficulties • Responds very well to anticholinesterase inhibitors • Atypical - Arthrogryposis Multiplex Congenita

12. DIFFERENTIAL DIAGNOSIS • Drug-induced myasthenia • Lambert-Eaton myasthenic syndrome (LEMS) • Neurasthenia • Hyperthyroidism • Botulism • Intracranial mass lesions • Progressive external ophthalmoplegia

13. ASSOCIATED DISORDERS • Disorders of the thymus : thymoma, hyperplasia • Other autoimmune disorders: Hashimoto's thyroiditis, Graves' disease, rheumatoid arthritis, lupus erythematosus, skin disorders, family history of autoimmune disorder

14. Factors causing muscle weakness • Physical exertion & emotional upset • Hot temperature • Infections • Hypo/hyperthyroidism • Pregnancy • Any surgery • Electrolyte disturbance • Drugs

15. Drugs increasing weakness • Antibiotics :  •  Aminoglycosides: e.g., streptomycin, tobramycin, kanamycin   • Quinolones: e.g., ciprofloxacin, levofloxacin, ofloxacin, gatifloxacin   • Macrolides: e.g., erythromycin, azithromycin, telithromycin • Nondepolarizing muscle relaxants for surgery :   d-TC (curare), pancuronium, vecuronium, atracurium • Beta-blocking agents : Propranalol, atenolol, metoprolol • Local anesthetics and related agents : Procaine, xylocaine,  Procainamide • Magnesium : ↓ ACh release

16. DIAGNOSIS • History • Diplopia, ptosis, weakness • Weakness in characteristic distribution • Fluctuation and fatigue: worse with repeated activity, improved by rest • Effects of previous treatments • Examination • Ptosis, diplopia, ice test • Motor power survey: quantitative testing of muscle strength • Forward arm abduction time (5 min) • Vital capacity • Absence of other neurologic signs

17. DIAGNOSIS (Contd…) • Investigations • Anti AchR radioimmunoassay - ~85% positive in generalized MG; 50% in ocular MG • Anti-MuSK antibodies - Seronegative pts ~40% • Edrophonium chloride (Tensilon) test • Repetitive nerve stimulation - decrement of >15% at 3 Hz • Single fibre electromyography shows increased jitter. • Chest X-ray : Lung tumour, thymoma • For ocular or cranial MG - CT/MRI (to exclude intracranial lesion)

18. Edrophonium test • 1-2mg of edrophonium test dose followed by 8mg IV administration can confirm the diagnosis. Improvement in ptosis

19. TREATMENT • Anticholinesterase drugs • 1st line of treatment • M/C used Pyridostigmine • Onset - 30 min • Peak - 120 min • Duration - 3-6 hrs • Max useful dose – 120 mg 3hrly • Higher dose – Cholinergic crisis - Skeletal msl weakness, salivation, miosis, bradycardia, abdominal cramps

21. TREATMENT (Contd…) • Immunosuppressive therapy • Corticosteroids • Azathioprine • Cyclosporine • Mycophenolate mofetil • Short term immunotherapy • Plasmapheresis • IV immunoglobulins • Thymectomy • Transcervical • Transsternal • VATS

22. MYASTHENIA SYNDROME(LAMBERT EATON SYNDROME) Autoimmune disease with IgG Abs against presynaptic voltage gated calcium channels Paraneoplastic syndrome small cell carcinoma of lungs Repetitive muscle activity improves strength Treatment – 3, 4 diaminopyridines – Immunosuppressive therapy Sensitive to both depolarizing & non depolarizing relaxants

25. Role ofAnaesthesiologists • For thymectomy • For any other surgery • ICU management – Myasthenic crisis

26. THYMECTOMY General principles Pre –operative- Medical stabilization of myasthenia Anesthetic – Avoid muscle relaxants Operative – Total thymectomy Avoid phrenic nerve injury Post operative – Multidisciplinary team Early extubation &resume medications.

27. Operative approaches • Transsternal Approach • Transcervical approach • Video assisted thoracoscopicthymectomy.

28. Peri-operative management For thymectomy to be an effective treatment modality in MG , total removal of thymus gland must be accomplished with minimal perioperative morbidity Thymectomy is never an emergency procedure. Preoperative medical stabilization is necessary.

29. Pre-operative Management Should be scheduled for elective surgery while in remission. Thorough review of neurological or bulbar involvement must be assessed Complete review of drug therapy must be done.

30. Neurologic assessment • Ensure optimal muscle power • Correct oropharayngeal , bulbar and respiratory muscle weakness by using any of the regimen • Anti-cholinesterase inhibitors • Corticosteriods • Immunosuppresants • Plasmapheresis.

31. Pulmonary evaluation • Assure presence of patent airways • Optimum respiratory muscle power • Adequate clearing of secretions and absence of respiratory infection • Pre-op test recommended- Chest X-ray ABG PFTs Chest CT if necessary • Can promote pre-op incentive spirometery.

32. Cardiac evaluation Basic tests : ECG , CXR Complete cardiac evaluation if pt has H/O IHD or other cardiac problems 2D ECHO when necessary Stress test when necessary

33. Concomitant medical conditions Infection Disorders associated with MG must be excluded, Thymoma ,Thyroid ds, ITP, Rheumatoid Arthritis, SLE, Pernicious Anemia/ Hemolytic Anaemia, Multiple Sclerosis, Ulcerative colitis, Leukaemia / Lymphoma, Scleroderma Distrubance in nutrition ,fluids and electrolytes

34. Check CBC and bleeding parameters Consider drug effects and drug interactions. Azathioprine can inhibit NDMR and extend effect of SCh Should pyridostigmine be continued or discontinued preoperatively?? Should corticosteriods be continued or discontinued preoperatively ??

35. Explain about post-op ventilation if : • MG duration > 6 yrs • Chronic resp illness • Pyridostigmine dose > 750 mg/day • Pre-op VC < 2.9L Others : • Bulbar symptoms • History of preopmyasthenic crisis • Serum anti Ach ab > 100nmol/L • Intraoperative blood loss greater than 1000ml

36. INTRAOPERATIVE- MANAGEMENT • First case in the list • Overnight fasting • Morning dose of anticholinesterase therapy continued / stopped ??? • If pt. on steroid therapy – perioperative coverage • Premedication • BZD – Midazolam, Diazepam • Opioids Avoided

37. ANAESTHETIC MANAGEMENT(Contd…) • Monitoring • Routine monitoring • Neuromuscular monitoring mandatory • Induction-TWO TECHNIQUES Non Muscle-relaxant or Balanced anesthesia • Thiopentone / Propofol in usual doses • Tracheal intubation usually achieved by inhalational agents • Fentanyl / lignocaine to blunt intubation response • Maintenance • O2 / N2O / Fentanyl / Inhalational agent / Thoracic epidural

38. ANAESTHETIC MANAGEMENT(Contd…) • TIVA can also be used • Muscle Relaxants • Succinylcholine – Resistant – larger doses(2.6times) • NDMR – Very sensitive – Dose 1/10th to 1/20th the normal dose • Reversal • Edrophonium / Neostigmine + Atropine / Glycopyrrolate

39. Extubation based on: Pre-op condition of patient Surgical technique Residual anesthesic effect Parameters of weaning include vital capacity >10ml/kg negative inspiratory force >20cm of H2O positive expiratory force >40cm of H2O

40. Regional anesthesia • If regional Anesthesia is used, anticholinesterase treatment potentiate ester type local anesthetics action. • Judicial dosing is essential in either type

41. Post-operative Management • Post- op care-CLOSELY MONITORED • Pain relief – IV opioids or epidural if present • Resume pyridostigmine(reduced dose) • I/V neostigmine till pt. able to take oral pyridostigmine • Mild resp depression – IV anticholinesterase • Importance of chest physiotherapy and breathing excercises is obvious

42. Thoracoscopicthymectomy Anestheic technique used is non muscle relaxant approach or balanced anesthesia without thoracic epidural Need DLT with OLV Less post-operative morbidity Minimal discomfort Rapid functional recovery Shorter hospital stay

43. Cholinergic v/s myasthenic crisis After thymectomy patients may become acutely sensitive to anticholinesterases and develop profound weakness from their use.This is cholinergic crisis When muscaranic effects are obvious, antimuscaranics and respiratory support are given. If muscuranic symptoms are absent, edrophonium test helps to distinguish.

44. Thank you