Myasthenia gravis CTVA presentation

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.

3. 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

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

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

6. 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.

7. Classification in Children

8. 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

9. 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

10. 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 1/30 th oral dose

11. 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

12. 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

13. 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.

14. 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.

15. 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  

16. 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.

17. 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)

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

19. 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

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

21. 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.

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

23. 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.

24. 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.

25. 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.

26. 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 .

27. 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 .

28. 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.

29. 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) .

30. 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.

31. For most surgical procedures,  Adequate relaxation by potent inhalational agents and, depth of anesthesia achieved with IV agents. 

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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).

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