Myasthenia Gravis

1. Anaesthesia for Myasthenia
Gravis
presenter: Dr. Kundan Kishor Ghimire
Moderator: Dr. Priska Bastola

2. Myasthenia Gravis(MG)
• an autoimmune disorder
• characterized by fatigable weakness of skeletal muscles.
• an antibody-mediated immunological attack directed at
acetylcholine receptors (or receptor-associated proteins).
• in post synaptic membrane of neuromuscular junction.

4. •Clinical Presentation
• fluctuating muscle weakness that worsens with exertion and
improves after a period of rest.
• occular muscle weakness(85%)
• ptosis- u/l, b/l, symmetric/asymmetric
• diplopia- intermittent

5. • weakness of face and throat muscles
• dysphagia
• dysarthria
• dysphonia
• myasthenia snarls
• limb muscle weakness (15%-20%)
• neck extensors> flexors
• upper limbs> lower limbs

6. • Respiratory muscle weakness
• dyspnea particularly in supine position
• weakness of the intercostal muscles and the diaphragm
• collapse the upper airway
• neurmuscular emergency- mechanical ventilation

7. • Epidemiology
• rare, incidence of approx 1 in 30,000 people
• women:men= 1.5:1
• Incidence: bimodal, varies with sex
• women: 2nd-3rd decade
• men:5th-6th decade
• higher incidence of autoimmune disease: autoimmune
thyroid disease, RA, SLE, DM.

10. Classification in Children

11. • Diagnosis
• History and clinical examination
• diagnostic tests
• Electrophysiologic tests:
• Repetative nerve stimulation test (RNS)
• single fibre electromyography(SFEMG)
• Pharmacologic tests: Edrophonium( Tensilon test)
• Serologic tests- Anti- AChR radioimmunoassay
• Anti-MuSK Abs

13. Myasthenia gravis treatments
•symptomatic treatment- anticholinesterase agents,
•chronic immunomodulating treatments-
glucocorticoids and other immunosuppressive
medication, and
•rapid immunomodulating treatments-
• plasmapheresis and intravenous immunoglobulin)
•Surgical Treatment

14. Anticholinsterase agents
Pyridostigmine,
•onset -15 to 30 mins,
•peak action:1-2 hours, duration: 3-4 hours.
•timing and dose is based on the patient’s symptoms.
•Dose: 30-120mg PO, then titrated to effect.
•IV dose in perioperative period, approx 1/30th oral dose

15. corticosteroids
•reduce AChR antibodies.
•Prednisolone: 15-20mg/day gradually increased to
60mg/day and alt day later
•onset of effect: 2-3wks
•maximal effect: 3-6 months

16. Immunotherapy —
• conjunction with corticosteroids and anticholinesterases.
• Azathioprine, cyclophosphamide, cyclosporine,
methotrexate, mycophenlate mofetil, and tacrolimus.
• Azathioprine
• 2-3mg/kg/day(total dose 100-250mg/day)
• onset of effect:3-12 months, maximal effects: 1-2 yrs

17. Plasmapheresis:
• removes Abs from circulation and produces short-term clinical
improvement.
• 3-4l/exchange
• 5 exchanges over 10-14 days period
• before thymectomy , during myasthenia crisis and periodically to
maintain remission.

18. Intravenous immunoglobulin
• rapid improvement for several weeks
• dose: 400mg/kg/day alternately for 5 days.
• MOA is unknown, no consistent effect on the measurable
amount of ACh receptor Abs.

19. Thymectomy
• thymoma and early-onset generalized MG in pt between
puberty and <60yrs.
• goal: induce remission, immunosuppressive medication
reduction.
• 50%-80% clinical improvement, and 21 %-38%: clinical
remission
• approach
• transsternal: better surgical exposure, 50% postoperative ventilation
• transcervical; minimally invasive, 10% postoperative ventilation
• other approaches : minimally invasive and combined transcervical- transternal

20. Preoperative Evaluation
• Elective surgery:
• stable phase
• minimal immunomodulatory medication or
glucocorticoids.
• routine preoperative evaluation.
• bulbar and respiratory symptoms,
• history of exacerbations or myasthenic crisis.
• surgery as early in the day as possible, when patient is strongest.

21. History:
• Bulbar symptoms (eg, dysphagia, dysarthria, nasal speech, or
low-intensity speech).
• History of myasthenic crisis and intubation.
• Respiratory muscle weakness, SOB.
• MG therapy.
• Associated diseases.(thyroid diseases, Anaemia, leukemia,
lymphoma)
• autoimmune diseases (eg, thyroiditis, RA, SLE)

22. Investigation:
• CBC
• RFT and serum electrolytes
• LFT
• Blood sugar level
• ABGs and PFT-
• CECT chest- for thymic mass

23. • Prediction of Postoperative myasthenia crisis:
• Risk factors —
• Vital capacity <2 to 2.9 L
• Duration of MG (>6 years)
• Pyridostigmine dosage >750 mg/day
• History of COPD.
• History of myasthenic crisis
• Intraoperative blood loss >1000 mL
• Serum antiacetylcholine receptor antibody >100 nmol/mL
• More pronounced decremental response (18-20 %) on low frequency repetitive
nerve stimulation

24. Anaesthetic management
• Avoid NMBAs whenever possible.
• Use ultrashort- or short-acting sedatives, hypnotics, and
anesthetic agents.

25. Premedication
• Metoclopromide, H2 blocker
• avoid premedication with sedatives.
• If necessary, smallest effective dose administered incrementally
(eg, midazolam 0.5 mg IV),
• continuous monitoring for bulbar weakness and respiratory
compromise.

26. Monitoring
• Basic monitoring: ECG, NIBP, SPO2, ETCO2, Temp
• ABGs
• Peripheral Nerve Stimulator

27. • Choice of anesthetic technique —
• local or regional anesthesia if possible.
• Regional anesthesia for peripheral procedures
• relatively low-level neuraxial anesthesia, either epidural or
spinal, or with peripheral nerve blocks.
• use amide local anesthetics over esters.

28. • Neuraxial anesthesia –
• Mid-thoracic or higher levels can result in accessory
muscle paralysis.
• Patients with preoperative respiratory compromise or
bulbar weakness may not tolerate.
• Brachial plexus blocks –
• Supraclavicular and interscalene brachial plexus blocks can
paralyze the diaphragm,
• for many hours, patients with respiratory compromise may
not tolerate.

29. • Induction and maintenance of anesthesia —
• Goals:
• prevent prolonged effects on respiratory and bulbar muscles,
and
• allow rapid recovery at the end of surgery.
• avoid NMBAs when possible.

30. • Inhalational agents –
• potent inhaled anesthetics(isoflurane, sevoflurane, desflurane)
• dose-dependent neuromuscular relaxation.
• adequate relaxation for endotracheal intubation and surgery.
• possibly equivalent to the level of relaxation achieved with
NMBAs in normal patients.
• Muscle strength recovers without reversal agents.

31. • Intravenous agents –
• IV anesthetics with or without small doses of NMBAs.
• Propofol, most commonly used for induction.
• TIVA with propofol infusion and remifentanil without NMBAs for
thymectomy.

32. • Remifentanil,
• an ultrashort-acting opioid, for intubation avoiding NMBAs.
• For a high-dose remifentanil intubation,
• propofol (2 mg/kg) plus remifentanil (4-5 mcg/kg)
• good to excellent intubating conditions at 2.5 minutes
after induction.

33. • Other IV agents
• to reduce the reflexes in response to laryngoscopy and
intubation while avoiding the administration of NMBAs.
• IV lidocaine (1 to 1.5 mg/kg IV),
• small doses of short-acting opioids (eg, fentanyl 50 to 100
mcg), and esmolol (10 to 50 mg) .

34. • Neuromuscular blocking agents (NMBAs) —
• avoid NMBAs unless absolutely necessary.
• rocuronium or vecuronium, and reverse with sugammadex.
• variable response to reversal, possibility of cholinergic crisis.
• anticholinesterase medication affects the degree of relaxation
and duration of NMBAs action.
• Monitor neuromuscular blockade using a quantitative TOF nerve
stimulator.

35. • For most surgical procedures,
1. Adequate relaxation by potent inhalational agents and,
2. depth of anesthesia achieved with IV agents.

36. • Depolarizing NMBAs(Succinylcholine) —
• variable response
• resistant: no anticholinesterase
• ED95 is 2.6 times normals (0.8 versus 0.3 mg/kg).
• prolonged effect:
• with anticholinesterase treatment
• as more SCh reaches motor endplate.

37. • Nondepolarizing NMBAs —
• extremely sensitive.
• available receptors are sufficient to produce endplate potential
above threshold
• for NM transmission and muscle contraction.
• Very small doses can result respiratory distress after emergence.

38. • 10% of usual dose.
• Guided by quantitative train-of-four nerve stimulator.
• steroidal NMBA to allow reversal with sugammadex.
• Mivacurium: prolonged paralysis in patients who have taken
pyridostigmine on the morning of surgery.

39. • Reversal of NMBAs —
• sugammadex rather than neostigmine.
• reversal if train-of-four ratio of >0.9 using a quantitative train-of-
four peripheral nerve stimulator.
• Sugammadex: 2-4mg/kg iv
• Neostigmine: if used titrated to effect to avoid cholinergic crisis.

40. • Extubation —
• short-acting anesthetics and multimodal analgesia.
• avoid medications that interfere with neuromuscular
transmission.
• adequate ventilation and oxygenation, strength, and the ability
to protect the airway.

41. Myasthenic crisis —
• severe respiratory muscle and/or bulbar muscle weakness
that necessitate intubation or to delay extubation.
• In awake patients, signs of impending crisis: dysphagia,
change in phonation, obstruction, weak cough, and difficulty
handling secretions.
• first sign: increase in RR with shallower tidal volume breaths.

43. • Use of accessory muscles or paradoxical movement of the
abdomen.
• Blood gases:
• hypocapnia in spontaneously breathing patients.
• increase (pCO2) is a sign of impending respiratory failure
• Treatment:
• delay extubation, as well as intensive care.
• plasma exchange or IV immune globulin, in addition to
immunomodulating therapy.

44. Cholinergic crisis —
• Patients receiving anticholinesterases are at risk.
• manifested by paradoxical weakness along with other signs
of cholinergic excess,
• after administration of an anticholinesterase for reversal.
• If suspected, atropine (0.4 to 2 mg IV) or glycopyrrolate (0.2
to 1 mg IV).

45. • References
• Morgan and Mikhail’s clinical anaesthesiology 6th edition
• Miller’s Anaesthesia 8th edition
• Barash’s clinical Anaesthesia, 8th edition
• Uptodate 2019