Muscle Disorders and General Anaesthetics

1. Muscle Disorders and General Anaesthetics Ben Creagh-Brown, UHL May 2004

2. Muscle disease (Myopathy ) can be divided into • Myositis – inflammatory disease • Muscular dystrophy – inherited disorder with progressive weakness • Myotonia - sustained contraction and slow relaxation • Channelopathies – disorders of ion channels within skeletal muscle cells

3. 3 main groups to be considered • Myasthenia Gravis and LEMS • Duchenne’s and Becker’s Muscular Dystrophy • Myotonic dystrophy

4. Myasthenia Gravis and LEMS • A 25 year old female presents for thymectomy for myasthenia gravis • What is myasthenia gravis? • Tell me as much as you know about it • How is it diagnosed? (include EMG) • What is edrophonium? • How does it work? • What dose should be used? • What are the symptoms? • How would you anaesthetise her?

5. Description • Myasthenia Gravis (MG) is an autoimmune condition in which IgG autoantibodies interact with the postsynaptic acetylcholine receptors (AChR) at the nicotinic neuromuscular junction (NMJ). • The AChR antibodies reduce the number of functional receptors by: • blocking attachment of ACh molecules • increasing the rate of degeneration of the receptors • complement-induced damage to the NMJ. • On average MG patients have 30% of the normal number of functional AChR.

8. Investigations

10. Treatments

11. Pyridostigmine • Analogue of neostigmine • More effectively absorbed from the gut • With equipotent doses, pyridostigmine has a slower onset and longer duration of action, and produces fewer gastrointestinal side effects than neostigmine • Patients may get the side effects of diarrhoea and abdominal cramps so they take atropine 0.5mg with each dose

12. Anaesthetic management • Avoid drugs that exacerbate MG • polymyxin antibiotics (such as colistin) block AChR but are rarely used anyway • Aminoglycosides decrease Ach release and AChR sensitivity and should be avoided • Procainamide exacerbate weakness • Quinine exacerbate weakness • Beta blockers exacerbate weakness

13. Pre operative assessment • Assessment of respiratory function (serial FVC on the ward) and bulbar weakness (SALT) • Chest physiotherapy • Optimise immunosuppression and anticholinesterase therapy • Consider IV Ig or plasma exchange • Consider ITU bed, prolonged ventilation post op more likely if: • Stage III or IV disease • Chronic respiratory disease • FVC <2.9l • Long history of disease (>6 years) • Exclude associated thyroid disease or DM • Airway ?RA ?Thymic mass compressing

14. On day of operation • Give anticholinesterases or not? Why? • Omit anticholinesterase therapy as this may prolong action of sux, require increased doses of non depolarising meuromuscular blocking drugs • Increased steroids, IV hydrocortisone

15. Induction and maintenance • Consider IABP as well as routine monitoring if sternotomy • Continuously monitor NM blockade • Intubate – need to protect the airway. Consider nasotracheal intubation if planned postop ventilation. • Some anaesthetists avoid IV induction and paralysis but intubate after deepening with inhalational agents only, MG patients are more susceptible to the muscle relaxant effect of volatile. • You may require more sux that usual and consequently get a Phase II block • Conversely they are exquisitely sensitive to non depolarising neuromuscular blocking drugs (NDNMB) Use 30-40% of the usual dose of vecuronium or atracurium. • Avoid reversing the NDNMB drugs to avoid the risk of cholinergic crisis

16. Post operative • Majority can be safely extubated and go back to the ward • HDU may be appropriate • ITU if ventilation required • Good analgesia including opiates.

17. LEMS • Lambert-Eaton Myasthenic Syndrome - a rare syndrome occurring in association with small cell carcinoma of the bronchus. • LEMS results from an autoimmune attack directed against the Voltage Gated Calcium Channels (VGCC) on the presynaptic motor nerve terminal (in 98% of those with cancer) • Antibodies have been found in the majority of patients with LEMS. • 3% of patients with SSLC. • Clinical features similar to MG but facial and bulbar muscles relatively spared • Distinguishing between the two diseases on EMG: Facilitation (strength improvement after exercise) is common in LEMS. Facilitation differentiates the 2 diseases only if it is noted after repeated testing of many separate muscle groups • They improve with the edrophonium test but not as markedly • Very sensitive to both depolarising and non depolarising drugs • There are other rare myasthenic syndromes including congenital

18. Duchenne’s Muscular Dystrophy • X linked recessive disorder, A third of cases are from a spontaneous mutation • 1 in 3000 live male births • Gene located at Xp21 region of X chromosome • Gene product is the protein Dystrophni, which is a cytoskeletal muscle protein • Clinical features of proximal limb weakness occur by the age of 4 and the diseases usually causes death by 20 years. • Becker’s MD is similar but milder and presents later.

19. Clinical features • Difficulty running • Gower’s sign of proximal leg weakness • Pseudohypertrophy of the calves • Myocardium is affected and a cardiomyopathy occurs • Usually disabled by the disease by 10 years of age

20. Investigations • Clinical diagnosis. Very high levels of CK. Muscle biopsy shows characteristic changes and immunochemistry confirm absence of dystrophin. EMG shows a myopathic pattern

21. Management • No treatment • Carrier detection: females with affected brothers have a 50% chance of carrying the abnormal gene. She are asymptomatic but have high CK levels, abnormal EMGs and muscle biopsies.

22. Anaesthetic implications • Weak respiratory muscles and kyphoscoliosis impair ventilation pre and post op • Cardiomyopathy and arrhythmias are common • Delayed gastric emptying and poor bulbar function predispose to aspiration • Rhabdomyolysis and an MH-like syndrome can follow use of Suxamethonium. • Very sensitive to depolarising and non depolarising muscle relaxants.

23. Myotonic dystrophy • Autosomal dominant disease. A triplet repeat disorder. • 1 in 20,000 • Characterised by myotonia = incomplete muscle relaxation after exercise. • Defect in sodium-chloride channels in muscle membrane • Onset around 20 to 50 years

24. Clinical features: • Muscle • Progressive distal muscle weakness • Ptosis and bulbar failure • Weak and wasted facial muscles and SCM • Myotonia • Cardiomyopathy and conduction defects • Central and Obstructive Sleep Apnoea • Non muscle • Cataracts, frontal baldness, mild learning difficulties, glucose intolerance, thyroid adenoma

25. Anaesthetic implications • Tolerate surgery very poorly • Myotonia can be precipitated by cold, shivering, mechanical or electrical simulation, suxamethonium and anticholinesterases (neostigmine) • Increased respiratory complications. • Keep normothermic • Monitor NM function • Increased sensitivity to thiopentone and propofol, suxamethonium and non depolarising muscle relaxants