Myasthenia gravis and anaesthesia

1. MYASTHENIA GRAVIS AND
ANAESTHESIA
PRESENTER: Dr Umang Sharma
MODERATOR: Dr Sailendra Sigdel

2. Introduction
• Myasthenia gravis : autoimmune disorder
• Characteriszed by fatigable weakness of skeletal muscles
• Weakness results from an antibody mediated immunological attack
directed at acetylcholine receptor or receptor associated protein in
the post synaptic membrane of the neuromuscular junction

4. Neuromuscular Physiology
• Neuromuscular junction (NMJ) : synapse or junction of axon terminal
of motor neuron with the motor end plate
• 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

5. • 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

6. Neuromuscular Transmission
1. Nerve action potential
2. Calcium entry into presynaptic
terminal
3. Release if Ach quanta
4. Diffusion of Ach across the cleft
5. Combination of Ach with post
synaptic receptor
6. Opening of Na/ k channel
7. Postsynaptic membrane
depolarization
8. Muscle AP

7. Incidence
• 2.1 to 5.0 per 100000 people in India
• More common in females
• M:F 4:6
• Peak incidence
• 2nd /3rd decade – female
• 5th decade - male

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

9. Etiopathogenesis
• Autoimmune disorder
• Autoantibodies to n-ACH receptor or muscle membrane proteins
• (TK/Rapsyn/Agrin)
• Autoantibodies damage NMJ by
• Activation and damage to muscle membrane
• Degrade n- ACH –R
• Blockade of ACH -R

10. Clinical Classification
• Pediatric MG
• Neonatal transient MG
• Babies born to mother with MG
• Circulation Ach-r antibodies passively transferred
• Present at 12-48 hrs after birth
• c/f feeble, poor cry, poor feeding effort ptosis and facial weakness
• Neonatal Persistent MG
• Very rare
• No detectable antibodies
• Juvenile MG
• Similar to adult MG

11. Adult MG (Osserman and Genkin)
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 muyscles
involvement

12. 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

13. Clinical Features
• Muscles weakness
• Fluctuating
• Worsens on exertion, improves with rest (hallmark)
• Ocular
• 1st manifestation
• Ptosis and diplopia
• Ptosis : symmetrical/ unsymmetrical , u/l or b/l
• Diplopia : nystagmus
• Pupil spared

14. • Bulbar Muscles
• Dysarthia / dysphagia
• Difficulty in chewing
• Nasal regurgitation and Nasal twang (palatal involvement)
• Involvement of facial muscle
• Myasthenic Snarl

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

16. Mass effect of MG associated with Thymoma
• Cough
• Dyspnea
• SVC syndrome
• Cardiovascular involvement
• Focal myocarditis
• LVDD
• A fib
• AV conduction delay

17. Factors aggravating MG
• Physical and emotional stress
• Infection
• Pregnancy
• Surgery
• Heat and exposure to bright sunlight
• Drugs : quinidine, CCB , B blocker , aminoglycosides, Phenytoin

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

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

20. Repeatitive Nerve Stimualtion Test
• Rapid decrease in amplitude of CMAP
• Single dose of edrophonium decrease decremental response

21. Single Fiber Electromyography
• More sensitive EPT
• Evaluates time interval between 2 muscles fiber AP in the same motor
unit

23. TENSILON TEST
• IV Edrophonium 1.2 mg (test dose ) given followed by 8mg iv
• Onset : 30 sec
• Duration : 10 min
• Patient with MG : drastic improvement

24. ICE PACK TEST
• Cooling improves neuromuscular transmission
• Placing ice pack for 2 min over eyelids causes resolution of ptosis

25. Serological tests
• Anti-ACH R antibodies
• 80% with generalized MG
• Preop level > 100nmol/l a/w postop myasthenic crisis
• MUSK antibodies

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

27. • Corticosteroids
• Reduces amount of ACH-R antibodies
• Prednisolone 1mg/kg or 40-60mg po on alternate days
• Immunosuppresants
• Azathioprine and cyclosporine
• ADR: nephrotoxic and hepatotoxic

28. • 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 MG
• Goal
• induce remission
• Reduce immunosuppressive medication
• C/I prepubertal child and pt with ocular symptoms only

30. Preoperative Assessment
• Preparation for elective surgery should be coordinated with
neurologist
• Elective surgery be performed stable phases of disease: to reduce the
chances of postoperative myasthenic crisis
• Assessment should be focused on patient bulbar and respiratory
symptoms
• Prior history of exacerbation should be noted

31. History
• Muscle involved with duration and severity
• Bulbar symptoms: aspiration
• History of myasthenic crisis and need for ET intubation
• Respiratory muscles weakness, SOB
• Ability to cough and maintain airway
• Total daily requirement of pyridostigmine should be known
• Patient with thymic mass : risk of airway compromise with induction
• Imaging studies ( CT Chest/ Xray ) should be reviewed

32. Lab Investigation
• CBC : if cyclosporine used
• TFT
• S. electrolyte
• BSL ( steroids)
• LFT
• KFT
• Preop ABG and PFT ( extubation)
• CT / MRI : Thymoma
• ECG : Pyridostigmine: bradycardia

33. Preoperative Preparation
• Should be admitted 24 hrs. prior to surgery
• Preoperative physiotherapy and incentive spirometry
• Patient should be informed preoperatively regarding need of
postoperative mechanical ventilation
• Duration > 6 years ----12
• COPD----------------------10
• Pyridostigmine > 750 mg/day----8
• VC <2.9 lit-----4
Levanthal Scoring
System
<10
>12

34. contined
• Anticholinesterase should be discontinued if mild symptoms or
continue in dependent patient
• risk of vagal arrhythmias
• Steroids continued
• Plasmapheresis : VC < 2lit
• Anti aspiration prophylaxis
• Opoids : best avoided

35. Choice of Anaesthesia
• Regional anaesthesia : considered
• Amide LA are preferred
• Anticholinesterases: impairs the hydrolysis of ester LA: prolonged
block

36. Induction
• Goal
• Prevent prolonged effect on respiratory and bulbar muscles
• Rapid recovery
• NMBA should be avoided when possible
Inhalation agent
• Provide dose dependent NM relaxation
• Adequate relaxation for ET intubation and surgery
• Recovery occurs as the inhalational agent is eliminated

37. Intravenous agents
• Used for induction and maintainence
• IV agents with short DOA : preferred
• Propofol : most commonly used (1-2mg/kg)
• Propofol + Remifentanil
• Iv Lidocaine or IV Esmolol may be used to reduce laryngoscopy reflex

38. Consideration for NMBD
Succinylcholine
• Variable response
• Pt not under anticholinesterase therapy : resistance to Sch
• Pt receiving Anticholinesterase :
• Decresed 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. Non depolarizing NMBD
• Extremely sensitive to NDMR
• ACH-R reduced > 70%
• Profound weakness to even precurarization dose
• Long acting NDMR avoided
• Atracurium / cis atracurium relatively safe
• Initial dose : reduced to 10 to 20 % normal dose

40. Monitoring
• Standard ASA monitoring
• Temperature
• Etco2
• Cvp if significant fluid shifts
• Urine output
• BSL
• 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. Maintainence
• Volatile anaesthetics with or without nitrous oxide
• Cisatracurium : preferred
• NMBD maintainence dose : 1/3 to 2/3 rd of intial dose
• Controlled ventilation

42. Extubation
Criteria:
• Pt can generate inspiratory pressure > -20mmhg
• Peak occlusion pressure > 30 cm of water
• FVC > 15ml/kg with sustained head lift > 5 sec
• Able to maintain normocapnia and adequate oxygenation
• Continuing mechanical ventilation until spontaneous recovery is
preferred over using reversal agent

43. • Reversal of neuromuscular blockage is recommended with
suggamadex
• Adequacy of reversal should be confirmed by TOF > 0.9

44. 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)
• 1st sign of impending crisis 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 IVIg

45. Prediction of Myasthenia Crisis
• Vital capacity < 2-2.9 lit
• Duration of MG > 6years
• Pyridostigmine >750 mg /day
• History of COPD
• Preooperative bulbar symptoms
• Intraoperative blood loss >1000ml
• Serum AntiACH-R Ab> 100nmol/ml
• 10 to 20 percent decremental response on nerve stimulation

46. Myasthenia Gravis vs. Myasthenic Syndrome
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

47. Thank You