1. MYASTHENIA GRAVIS ANESTHESIOLOGY Jasdeep Dhaliwal Clinical Rotation

2. Overview  Pathophysiology  Autoimmune disease producing autoantibodies against nicotinic acetylcholine receptors at the NMJ  Bulbar symptoms most common Ptosis, Diplopia, Blurred vision Drooling, difficulty chewing, swallowing, facial weakness, dysarthria, and dysphagia  Weakness worsens with activity and fluctuates throughout the day  Muscle weakness leads to increased risk of aspiration, respiratory failure and cardiomyopathy  Does not affect smooth muscle or neuronal nicotinic acetylcholine receptors No autonomic dysfunction  Hyperplasia of thymus seen in 65% of patients Antibodies produced in Thymus

3. Picture!

4. Classification  Type I  Extraocular muscle only  Type IIa  Mild with sparing of respiratory muscles  Type IIb  Rapidly progressive involving respiratory muscles  Type III  Acute onset and rapid progression  Type IV  Severe form

5. Overview  Diagnosis  Edrophonium test Short acting acetylcholinesterase inhibitor Improvements seen in 5 minutes and last 10 minutes  Autoantibodies detected in serum  Electromyography Classic decrement in action potential after successive nerve stimulation

6. Treatment  Acetylcholinesterase Inhibitors – first line  Pyridostigmine  Thymectomy  Improves symptoms, remission rate and clinical course  Immunosuppressants  Decreases production of autoantibodies  Plasmapheresis  Physical Therapy  Especially after crisis

7. Myasthenic Crisis vs. Cholinergic Crisis  Mysathenic Crisis  Serious complication where patients are unable to breathe adequately and possibly develop respiratory failure  Impaired swallowing and managing of secretions leading to aspiration  Monitory NIF, vital capacity, tidal volume  Cholinergic Crisis  Due to and excess of acetylcholine at the NMJ as seen in organophosphate poisoning  Fasiculations, sweating, myosis, abdominal pain, bradycardia  Flaccid paralysis and respiratory failure  Differentiate with edrophonium test

8. ANESTHETIC CONSIDERATIONS  PFT’s suggested to determine whether post-op intubation will be required  Monitor NIF, vital capacity and tidal volumes  Myasthenia gravis patients have decreased respiratory reserve so depressant drugs should be used with caution

9. ANESTHETIC CONSIDERATIONS  Myasthenia gravis patients are extremely sensitive to non-depolarizing blockers Dose-response for vecuronium in normal patients and patients with myasthenia gravis. (Reprinted from Eisenkraft JB, Book WJ, Papatestas AE: Sensitivity to vecuronium in myasthenia gravis: A dose- response study. Can J Anaesth 1990: 37: 301–306

10. ANESTHETIC CONSIDERATIONS  Cholinesterase inhibitor drugs used to treat myasthenia will influence the response to both depolarizing and non-depolarizing muscle relaxants  Although patients with myasthenia have a resistance to succinylcholine, a dose of 1.5 to 2 mg/kg will be adequate for rapid tracheal intubation. Preoperative administration of pyridostigmine, however, may prolong the duration of action of succinylcholine  Monitoring neuromuscular function with nerve stimulation is not always reliable in patients with MG

11. Notable Patients  Aristotle Onassis  Christopher Robin Milne  Brandon Cox

12. Resources  Miller’s Anesthesia, 7 th ed.  Clinical Anesthesia, 6 th ed. – Paul Barash  Big Blue Book