Anesthesia for Thymectomy

1. Anesthesia for Thymectomy Rami Wahba, M.D Lecturer of Anesthesia Ain Shams University

2. Introduction • The pathophysiological role of the thymus in myasthenia gravis, and the mechanism of therapeutic effect of thymectomy, are incompletely understood. • Nevertheless, thymectomy is a valuable treatment modality in selected patients with generalised myasthenia gravis.

3. There are several types of thymectomy operation, but no one operative approach is clearly superior to the others. • To minimise operative morbidity, surgery for myasthenia gravis requires a multidisciplinary (neurology, surgery, anaesthesia) approach to perioperative care.

4. Myasthenia gravis is an autoimmune disease characterised by muscular weakness and fatigability. • Thymectomy plays a central role in the treatment of myasthenia gravis.

5. Pathogenesis of myasthenia gravis • The weakness of myasthenic patients is due to an antibody-mediated autoimmune attack against acetylcholine receptors at neuromuscular junctions. • This autoimmune process causes a reduction in the number of acetylcholine receptors and reduced transmission of neural signals to skeletal muscle.

6. Reduction of acetylcholine receptors is a reversible process; receptors regenerate if the autoimmune process is controlled. • Anti-acetylcholine receptor antibodies are produced by B cells, but T cells and other immune cells are important for B cell stimulation and antigen processing.

7. The thymus gland plays a central role in the pathophysiology of myasthenia gravis. • It contains the key cellular elements of the myasthenic autoimmune process (antigen presenting cells, T cells, and B cells).

8. Clinical features, diagnosis, and medical treatment • Myasthenia gravis a bimodal age distribution; young adult females and older adults of both sexes are typically affected. • Skeletal muscle weakness, and fatigability with repetitive activity, are characteristic.In most patients, extraocular and eyelid muscle weakness are the first symptoms of disease.

9. Generalised weakness develops in 85% of patients. • If weakness of the diaphragm and accessory muscles is severe, mechanical ventilation is required (myasthenic crisis). • Before the widespread use of immunosuppressive therapy and thymectomy, approximately 25% of patients with myasthenia gravis died of their disease.

10. No single investigation is diagnostic of myasthenia gravis. • the diagnosis is confirmed by a combination of anticholinesterase testing, electrophysiological testing, and antiacetylcholine receptor antibody assay. • Once a diagnosis of myasthenia gravis is made, patients should have a screening chest computed tomography (CT) scan for possible thymoma

11. Medical therapies for myasthenia gravis can be classified into three groups: -anticholinesterase drugs -immunosuppressive drugs -short-term immunotherapies (plasmapheresis and immunoglobulin)

12. Second-line medical therapies and surgical thymectomy should not be viewed as competitive treatment modalities. • Immunosuppressive therapy + thymectomy are often used together, in a complementary fashion.

13. Thymectomy: general principles -Pre-operative • Medical stabilization of myasthenia -Anaesthesia: • Avoid muscle relaxants. -Operative: • Total thymectomy. • Avoid phrenic nerve injury.

14. -Postoperative: • Multidisciplinary team. • Early extubation. • Resume anticholinesterase medication (reduced dose)

15. Thymectomy • The goal of thymectomy in myasthenia gravis is to cause remission of disease . or • to allow dose reduction of potentially harmful immunosuppressive drugs. • Most experienced clinicians recommend thymectomy for patients with mild or moderate generalised disease.

16. Patients with acute-severe generalized myasthenia may benefit from thymectomy, but they require initial intensive medical therapy to stabilise their condition. • All myasthenics suspected of having a thymoma should undergo thymectomy for oncological reasons

17. Operative Approaches *Sternotomy • Technically simple • Cosmetic concerns; pulmonary morbidity *Transcervical • Cosmetically good; minimal morbidity • Technically difficult; risk of subtotal thymectomy

18. *Maximal (sternotomy + cervical) • Most complete resection • Highest morbidity; two incisions; risk of recurrent laryngeal nerve injury. *Thoracoscopic • Cosmetically good; reduced incisional pain? • Technically difficult; risk of subtotal thymectomy; post thoracoscopy neuralgia

19. General principles of peri-operative management: peri-operative management • For thymectomy to be an effective treatment modality in myasthenia gravis, total removal of the thymus gland must be accomplished with minimal perioperative morbidity. • Thymectomy is never an emergency operation. Pre-operative medical stabilization of myasthenic symptoms is necessary.

20. What are the steps to follow during pre-operative management? • Ensure optimum muscle power.correctoropharyngeal, bulbar and respiratory muscle weakness using the following regimen: • anti-cholinesterase inhibitors (pyridostigmine, neostigmine). • corticosteroids (prednisone, prednisolone)

21. c) other immunosuppressants when these become necessary. Use of these, however, may require several weeks to several months before optimum therapeutic benefit is obtained. d) plasmapheresis or intravenous immune-globulin in patients with moderate to severe bulbar and respiratory muscle weakness or in patients with a high titer of anti-Acetylcholine Receptor antibodies.

22. 2. Acquire adequate pulmonary evaluation and clearance to: - assure presence of patent airways -optimum respiratory muscle power -adequate clearing of secretions and absence of respiratory infection. The following pre-operative tests are recommended: a) chest x-ray b) arterial blood gases

23. c) pulmonary function test (including FVC, FEF, flow-volume loop) ,preoperative (FVC) and a (FEF) between 25 and 75% of FVC (FEF25-75%) were noted to be of important value to predict the need for postoperative ventilation. d) sputum G/S, C/S when necessary e) chest CT scan when necessary

24. Perform cardiac evaluation as follows: a) basic tests: ECG, chest x-ray; b) complete cardiology evaluation if - if patient has history of ischemic heart disease,other cardiac problems or risks for developing cardiac problems. c) 2D echocardiography when necessary d) stress test when necessary

25. Search for and adequately treat concomitant medical conditions: a) Infection b) Disorders associated with MG. Do the following tests: - ESR - thyroid function tests - blood sugar - ANA - rheumatoid factor c) Disturbance in nutrition, fluids and electrolytes

26. 5.Check CBC and bleeding parameters (CT, BT, PT, PTT). 6. Consider drug effects and drug interactions. If the patient is on medications, ensure that there are no side effects of these drugs or adverse drug reactions that may interfere with or complicate the intra- and post-operative course of the patient.

27. Interaction with Other Drugs

28. Should pyridostigmine be continued or discontinued pre-operatively? Pyridostigmine or other anticholinesterase may be continued pre-operatively if the patient derives improved muscle strength with its use.

29. The following guidelines are recommended: 1. To allow a decrease in the blood level pre-operatively, give pyridostigmine or anticholinesterase 4 to 6 hours pre-operatively. Pyridostigmine may be resumed post operatively. 2. Pyridostigmine may cause increase in oral and tracheal secretions especially in intubated patients. This can be titrated to avoid or minimize problems in post-operative pulmonary toilet.

30. Omitting pyridostigmine pre-operatively may reduce the need for muscle relaxant as well as lessen the effect of ester anesthetic agents. • However, the omission of the pyridostigmine on the day of surgery predisposed myasthenic patients to the possibility of respiratory discomfort and sensitivity to vecuronium.

31. Should corticosteroids be continued or discontinued pre- and peri- operatively? • Steroids should be continued pre-operatively in steroid-dependent patients. • Steroid-dependent patients have the possibility of developing post-operative deterioration or crisis so they will require pre- and peri-operative coverage. • Steroids also decrease dose of non-depolarizing relaxants.

32. Maintain adequate post-operative pain control. Avoid muscle relaxants and tranquilizing drugs. Maintain adequate pulmonary toilet and physical therapy Avoid or use very cautiously drugs interfering with neuro-muscular transmission

33. Anesthesia for thymectomy What is the recommended anesthetic management? 1. Anesthesiologists must consider the patient’s disease severity including: - voluntary and respiratory muscle strength - ability to protect and maintain patent airway post-operatively - the type of surgical procedure. - patient’s ongoing medication e.g steroids.

34. For pre-operative medications: Generally, anxiolytics, sedatives and opioids are rarely given to patients with little respiratory reserve. Small dose benzodiazepines, when necessary, may be given to patients with good respiratory reserve.

35. Choice of anesthetic agents: The anesthesiologist must confer with the neurologist and the surgeon . There are several anesthetic agents that can be used .There is no anesthetic technique that is superior to others. These techniques have included:

36. The different anesthetic techniques for thymectomy are classified into: 1)non-muscle relaxant techniques. -Avoidance of muscle relaxants and use of potent inhaled anesthetics both for facilitating tracheal intubation and providing relaxation for surgery. -Myasthenic patient is sensitive to non-depolarizing neuromuscular blockers (NMBs) and resistant to depolarizing NMBs.

37. 2)Muscle relaxant technique: -Intermediate and short acting non-depolarizing NMBs can be used in myasthenic patients monitored with mechanomyogram. • Long acting NDNMB (pancuronium, pipecuronium, doxacuronium) :avoided • Intermediate and short acting: used with careful monitoring. Single twitch (0.1-1Hz), Train-of-four(2Hz), Tetany(50-100Hz), Double-burst stimulation.

38. -Depolarizing Neuromuscular Blocker (Succinylcholine): • MG patients show resistance to depolarizing agents. • MG patients are more likely to develop phase II block , particularly with repeated doses of succinylcholine.

39. Inhalation anesthetics may produce muscle relaxation in myasthenic patients. Isoflurane and sevoflurane were reported to produce muscle relaxant effect in myasthenic patient. • Isoflurane , enflurane: decrease TOF responses • Sevoflurane at 2.5% depresses EMG responses ( T1/Tc at 47%, T4/T1 at 57%). The rapid kinetic (low blood gas solubility coefficient) of sevoflurane allowed fast recovery of consciousness, airway reflexes and respiratory function at the end of surgery

40. 3)Use of total intravenous anesthesia (TIVA). • Propofol • Anesthetic management using propofol without untoward effects have been described. • Short duration, no effect on NM transmission. • Propofol obtund airway reflexes and allow a relatively easy intubation in the majority of patients. • Opioid • do not appear to depress NM transmission in MG muscle. • Central respiratory depression may be a problem. • Use of short-acting opioids : more titratable. Remifentanil (elimination half-life:9.5min)

41. 4)Use of local or regional anesthetic techniques: -It was adopted by El dawlatly et al in 1994 for maximal thymectomy . -It consists of the insertion of thoracic epidural analgesia in an awake patient prior to induction of general anesthesia .

42. Potentiation of NM blockade by local anesthetics has been reported. • Decrease sensitivity of the postjunctional membrane to Ach. • Ester anesthetics, metabolized by cholinesterase, may present particular problems in patients taking anticholinesterases. • Use reduced doses of amide (lidocaine, bupivacaine) to avoid high blood levels.

43. -Anesthesia is induced with opioid followed with propofol . -Anesthesia is maintained using 60% N2O/O2, propofol infusion 6-12 mg/kg b.w and epidural bupivacaine 0.125% infusion 4-6 ml/hr. -This technique eliminates the need of NMBs and epidural offers better intra and postoperative pain control in addition to on table extubation of the trachea.

44. There is need to monitor patients especially noting interactions of the anesthetic agents with other drugs and keeping in mind the variable responses the myasthenic patients may have to the anesthetic drugs.

45. Currently, there is increasing interest in VATT in MG. • Thoracoscopic thymectomy offers several advantages : -less postoperative morbidity. -minimal discomfort. -rapid functional recovery. -shorter postoperative hospital stays.

46. El dawlatly et al 2008 provide an anesthetic technique for VATT which includes: -non-muscle relaxant approach -intubating the trachea with double lumen tube after topical spray to vocal cords -continuous infusion of propofol and sufentanil. Associated with one lung ventilation .

47. During earlier phases of VATT, they use the same non-muscle relaxant technique combined with thoracic epidural anesthesia . • However, later the technique has been modified to be non-muscle relaxant without thoracic epidural anesthesia.

48. What is the recommended post-operative management? • Closely monitor at Post-Anesthesia Care Unit or Surgical Intensive Care Unit Respiratory support can be immediately instituted. • Predict as accurately as possible the best time to extubate or continue on mechanical ventilation based on: - Pre-operative condition of the patient - Surgical technique used

49. -Residual anesthetic effect - Parameters for weaning include: .absence of crisis triggers . objective findings showing adequate muscle power .vital capacity > 10 ml/kg .negative inspiratory force > 20 cm water .positive expiratory force > 40 cm water.

50. After thymectomy, patients may become acutely sensitive to anticholinesterases, and develop profound weakness from their use. This is called a Cholinergic Crisis (excess of Ach at nicotinic and muscarinic receptors). • Nicotinic overstimulationtwitching, fasciculations, weakness . • When muscarinic effects are obvious , diagnosis is easily made. Antimuscarinics and respiratory support are given.