Myasthenia gravis presentation uma.pptx

useful for pgs and technicians. patients come practical points useful when myasthenia

1. Anaesthetic Implications in Myasthenia gravis Dr.G.Uma Associate Professor Dept of Anaesthesiology Karpaga Vinayaga Institute of Medical Sciences & Research Center Madurantagam,Tamilnadu

2. Introduction Myasthenia gravis is an autoimmune disorder, characterized by fatigable weakness of the skeletal muscles resulting from an antibody mediated immunological attack directed at acetylcholine receptor or receptor associated protein in the post synaptic membrane of the neuromuscular junction.

3. There are auto antibodies to Acetyl choline receptors. These auto antibodies are against α subunit of the muscle type nicotinic Ach(acetyl choline)receptors ,present only at muscles. That’s why there is sparing of CNS and autonomic receptors. auto antibodies to muscle specific tyrosine kinase(MUSK-Ab)or lipoprotein related protein (LR P4) have also been identified.

4. Normal Neuro muscular junction

5. Anatomy of NMJ

6. Neuromuscular Physiology Neuromuscular junction (NMJ) is a synapse or junction of axon terminal of motor neuron with the motor end plate It is responsible for initiation of AP across the muscles surface The NMJ is specialized on the nerve side and on the muscles side to transmit and receive chemical messages As nerve axon approaches the muscles, it branches repeatedly to contract many muscle cells and gather them into a functional group known as motor unit

7. The nerve is separated from the surface of the muscles by a gap of approx. 20nm , called the junctional or synaptic cleft. The nerve and muscles are held together in tight alignment by protein filament called basal lamina The muscle surface is heavily corrugated with deep invagination of the junctional cleft- the primary and secondary clefts

8. Formation of an action potential & muscle contraction

9. Neuromuscular Transmission Nerve action potential Calcium entry into presynaptic terminal Release if Ach quanta Diffusion of Ach across the cleft Combination of Ach with post synaptic receptor Opening of Na/ k channel Postsynaptic membrane depolarization Muscle AP

10. NMJ in Myasthenia gravis

11. Etiology & pathogenesis Autoimmune disorder with Autoantibodies to n-ACH receptor or muscle membrane proteins(TK/MUSK Ab/LR P4) . Autoantibodies damage NMJ by Activation and damage to muscle membrane Degradation of ACH –R Blockade of ACH -R

12. Incidence 2.1 to 5.0 per 100000 people in India More common in females M:F 4:6 Peak incidence 2 nd /3 rd decade – female 5 th decade – male 10% of the patients may present with a thymoma .70% of the patients may have thymic hyperplasia.MG Is initiated with in thymus by immunogenic presentation of locally produced nicotinic AchR to potentially auto immune T cells .

13. Associated autoimmune disorders Rheumatoid arthritis SLE DM Autoimmune thyroid disease SIADH Cushing Syndrome RBC aplasia Hypogammaglobinemia

14. Clinical Classification

15. Adult MG ( Osserman and Genkin classification) Class Name Description I Ocular Myasthenia Involves ocular muscles only Ptosis and Diplopia Electrophysical test : Negative GENERALIZED MG Iia MILD Slow onset Usually ocular Spreading to bulbar or skeletal muscles Good response to drug IIb MODERATE Slow onset Ocular with more severe involvement of peripheral muscles Dysarthia / Dysphagia No respiratory muscles involvement

16. Class Name Description III Acute Fulminating MG Rapid onset Progresses within 6 months Severe bulbar and skeletal muscles involvement Involves respiratory muscles Poor response to treatmnt IV Late Severe MG Develops 2 years after onset Severe bulbar and skeletal muscle involvement Involves respiratory muscles Poor response III A Predominantly limb, axial or both. III B Predominantly oropharyngeal/Respiratory

17. Clinical Features Muscles weakness Fluctuating Worsens on exertion, improves with rest (hallmark) Ocular 1 st manifestation Ptosis : symmetrical/ Asymmetrical Diplopia :unilateral/Bilateral nystagmus Pupil spared

18. Clinical features continued Bulbar Muscles Dysarthia / dysphagia Difficulty in chewing Nasal regurgitation and Nasal twang (palatal involvement) Involvement of facial muscle Myasthenic Snarl

19. Limb Muscles involvement Proximal muscles > distal Difficulty in climbing Weakness of neck extensors Dyspnea – resp muscles Diaphragmatic involvement : reduced forcefulness to cough Difficulty to produce voice

20. Mass effect of MG associated with Thymoma Cough Dyspnea SVC syndrome Cardiovascular involvement Focal myocarditis LVDD Atrial fibrillation AV conduction delay

21. Factors aggravating Myasthenia gravis Physical and emotional stress Infection Pregnancy Surgery Heat and exposure to bright sunlight Drugs : quinidine, CCB , B blocker , aminoglycosides, Phenytoin,Fluroquinolines

22. Diagnosis Clinical Examination Fatigue after prolonged upward gaze and holding outstretched hand in abduction Decreased vital capacity Absence of other neurological signs

23. Electrophysiological Tests Peripheral nerve stimulated Decrease in twitch response of 10% between 4 th and 1 st twitch Is Diagnostic

24. Repeatitive Nerve Stimualtion Test Rapid decrease in amplitude of CMAP

25. Single Fiber Electromyography More sensitive test. Evaluates time interval between 2 muscles fiber action potential in the same motor unit

26. Tensilon test Single dose of edrophonium decreases decremental response. IV Edrophonium 1.2 mg (test dose ) given followed by 8mg iv. Onset : 30 sec Duration : 10 min. Patient with MG : drastic improvement seen. Serological tests Anti-ACH R antibodies& MUSK antibodies 80% with generalized MG. Preop level > 100nmol/l associated with postop myasthenic crisis. Ice pack test Cooling improves neuromuscular transmission. Placing ice pack for 2 min over eyelids causes resolution of ptosis.

27. Treatment Anticholinesterase 1 ST line of treatment Pyridostigmine : 30 to 120 mg/day in 3-6 divided dose Onset 30 min Side effects : cholinergic crisis

28. Treatment contd Corticosteroids Reduces amount of ACH-R antibodies Prednisolone 1mg/kg or 40-60mg po on alternate days Immunosuppressants Azathioprine and cyclosporine ADR: nephrotoxic and hepatotoxic Plasmapheresis Removes circulating antibodies from plasma Intravenous Immunoglobulins Rapid improvement Used to treat myasthenic crisis

29. Surgery :Thymectomy Based on the retrospective data 50-80% : clinical improvement Indicated in patient with generalized Myasthenia gravis Goal is to induce remission & Reduce immunosuppressive medication C/I prepubertal child and patients with ocular symptoms only

30. Preoperative Assessment Preparation for elective surgery should be coordinated with the Neurologist Elective surgery to be performed during stable phases of disease/remission: to reduce the chances of postoperative myasthenic crisis Assessment should be focused on patient’s bulbar and respiratory symptoms( Osserman Grading) Prior history of exacerbation should be noted Assessment of thymoma if present

31. History Muscle involved with duration and severity Bulbar symptoms: h/o aspiration History of myasthenic crisis and need for ET intubation Respiratory muscles weakness, h/o breathlessness Ability to cough and maintain airway Total daily requirement of pyridostigmine Patient with thymic mass : risk of airway compromise with induction

32. Investigations CBC : if cyclosporine used TFT S. electrolytes, serum Ca levels BSL ( steroids) LFT KFT Preop ABG and PFT –vital capacity CT / MRI : Thymoma Imaging studies Chest Xray ECG : bradycardia

33. Preoperative Preparation Should be admitted 24 hrs. prior to surgery, consent taken for post op ventilation Preoperative physiotherapy and incentive spirometry are to be started Drugs that may precipitate myasthenic crisis(to be avoided ) are fluroquinolones, Phenytoin, β blockers, Ca channel blockers, Ketamine, NM blockers, Ach agents Anticholinesterase should be discontinued if mild symptoms or continue in dependent patient(remember risk of arrhythmias) Steroids to be continued Pre op Plasmapheresis : if VC < 2lit

34. Scoring systems to predict crisis/post op ventilation Leventhal Scoring System –four parameters Duration > 6 years ---- 12 score of <10 or >12 COPD----------------------10 Pyridostigmine > 750 mg/day----8 VC <2.9 lit-----4 MGFA-PIS scoring based on the treatment and symptoms. If on immunosuppressants/remission.

35. Other Scoring systems Scoring system by Giovanni et al (2014) .four parameters ,to predict post op mechanical ventilation are Osserman stage (I IIA IIB III-IV) BMI (<28 >28) Duration of symptoms ( <1 1-2 >2 years) Associated with pulmonary resection (yes or no)

36. Choice of Anaesthesia Regional anaesthesia is preferred wherever possible. Anticholinesterases impair the hydrolysis of ester LA drugs.so amide LA drugs are to be used.( but prolonged action).Remember Respiratory muscle weakness when planning Brachial plexus blocks. Analgesics- short acting opioids, remifentanil /Fentanyl

37. Induction agents- propofol, thiopentone. With a goal to Prevent prolonged effect on respiratory and bulbar muscles & enhance Rapid recovery avoid ketamine Inhalation agents(sevoflurane>isoflurane) are preferred as they Provide dose dependent NM relaxation Adequate relaxation for ET intubation and surgery Recovery occurs as the inhalational agent is eliminated

38. NM blockers- Variable response Pt not under anticholinesterase therapy : resistance to Sch Pt receiving Anticholinesterase : Decreased plasma cholinesterase Decreased metabolism of Sch Increased DOA of Sch Phase II block occurs on normal doses due to rapid desensitization of motor end plate

39. Extremely sensitive to NDMR ACH-R reduced > 70% So Profound weakness to even precurarization dose avoid Long acting NDMR. Rocuronium can be used as it can be reversed with Sugammadex . Atracurium / cis atracurium are relatively safe Initial dose : reduced to 10 to 20 % normal dose Cis atracurium is preferred because of short elimination half life, small volume of distribution, lack of cumulative effect & high clearance

40. Peri operative Monitoring Standard ASA monitoring=Spo2.NIBP,ECG, Temperature,Etco2 CVP if significant fluid shifts are expected IABP (Major surgeries) Urine output Neuromuscular monitoring at one or more site due to uneven muscle weakness (Response to orbicularis oris is reduced more than adductor pollicis due to ocular involvement )

41. Maintenance & Extubation Volatile anaesthetics with or without nitrous oxide NMBD maintainence dose : 1/3 to 2/3 rd of intial dose Controlled ventilation Epidural / nerve blocks for post op pain relief Fluids as per need Extubated if 1. Pt can generate inspiratory pressure > -20mmhg 2. Peak occlusion pressure > 30 cm of water 3. FVC > 15ml/kg with sustained head lift > 5 sec 4.Able to maintain normocapnia and adequate oxygenation Continuing mechanical ventilation until spontaneous recovery is preferred over using reversal agent

42. Reversal of neuromuscular blockage is recommended with sugammadex Adequacy of reversal should be confirmed by TOF > 0.9 Sugammadex acts in the plasma , not at the NMJ.it encapsulates rocuronium in the plasma.depends on concentration gradient of rocuronium at NMJ and in plasma.Rocuronium diffuses away from NMJ in to the plasma where it is chelated by sugammadex

43. Criteria for reintubation post op Respiratory rate >40/mt Respiratory acidosis inspite of not using opioids Vital capacity <8ml/Kg Chest X ray shows Atelectasis Maximum static expiratory pressure can be used as a marker to predict post operative myasthenic crisis

44. Prediction of Myasthenia Crisis Bulbar involvement & Rapid progression of disease 2. h/o prior myasthenic crisis 3. VC <2.9 l 4. BMI >28 5. Pyridostigmine>750mg/day 6. Duration of symptoms> 6 years 7. History of COPD 8. Intraoperative blood loss >1000ml 9. Serum AntiACH -R Ab > 100nmol/ml

45. Myasthenic Crisis Defined as respiratory muscles and / or bulbar muscle weakness severe enough to necessitate intubation or to delay extubation after surgery Can occur spontaneously with the stress of surgery, or as a result of a number of precipitants ( infection, residual anesthetics) 1 st sign of impending crisis is increase in RR with shallow TV Treatment : coordinated with neurologist If weakness is present at the end of surgery: delay extubation Urgent rapid therapy with plasmapheresis or IV Immunoglobulins

46. Cholinergic crisis Due to overtreatment with anti cholinergics Flaccid muscle weakness Miosis SLUDGE syndrome( salivation,lacrimation,urinary incontinence,diarrhea,GI upset & emesis) Intubation & ventilation IV Ig 400mg/Kg/ dy for 5 days Plasmapheresis Immunomodulation Prednisolone 60-80mg/day Cyclosporine/Azathioprine Plan Weaning from ventilation

47. Myasthenia Gravis vs. Myasthenic Syndrome differential diagnosis Characteristics Myasthenia Gravis Myasthenic Syndrome Gender Female Male Presenting Sign Weakness of ocular , bulbar , facial muscle Limb muscles weakness (legs more than arms) Pathology a/ w thymoma 15-20% a/w scc Reflexes Normal Decreased Electrophysical test Voltage decrement on repeated stimulation Voltage increment Response to muscles relaxant Sch : variable NDMR : increased sensitivity Sch : increased sensitivity NDMR : normal Presence of Ab Ab against Ach-R Ab against Ca ++ channel

48. Summary MG is an autoimmune disorder of the NMJ resulting in muscle weakness, often bulbar symptoms may be there. treatment includes anticholinesterases, steroids& Immuno suppressants. The Anesthetic concerns are to use ultra short acting sedatives, induction agents& analgesics. resistance to depolarising NMBAs & Sensitivity to non depolarising NMBAs warrant the use of Rocuronium which can be reversed with sugammadex . Neuromuscular monitoring is a must intra operatively. Elective ventilation may be needed for some patients. Its crucial that myasthenic crisis is diagnosed and treated in time.