Anesthesia for Thymectomy by 5bS7l4


									Anesthesia for Thymectomy

     Rami Wahba, M.D
      Lecturer of Anesthesia
     Ain Shams University
• 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.
• 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.
• Myasthenia gravis is an autoimmune disease
  characterised by muscular weakness and

• Thymectomy plays a central role in the
  treatment of myasthenia gravis.
  Pathogenesis of myasthenia
• 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.
• 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.
• 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).
  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.
• Generalised weakness develops in 85% of

• 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.
• No single investigation is diagnostic of
  myasthenia gravis.

• the diagnosis is confirmed by a combination of
  anticholinesterase testing, electrophysiological
  testing, and antiacetylcholine receptor antibody

• Once a diagnosis of myasthenia gravis is made,
  patients should have a screening chest
  computed tomography (CT) scan for possible
• Medical therapies for myasthenia gravis can be
  classified into three groups:
-anticholinesterase drugs
-immunosuppressive drugs
-short-term immunotherapies (plasmapheresis
  and immunoglobulin)
• 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
• Thymectomy: general principles
• Medical stabilization of myasthenia

• Avoid muscle relaxants.

• Total thymectomy.
• Avoid phrenic nerve injury.
• Multidisciplinary team.
• Early extubation.
• Resume anticholinesterase medication (reduced
• The goal of thymectomy in myasthenia gravis is
  to cause remission of disease .
• to allow dose reduction of potentially harmful
  immunosuppressive drugs.

• Most experienced clinicians recommend
  thymectomy for patients with mild or moderate
  generalised disease.
• 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
     Operative Approaches
• Technically simple
• Cosmetic concerns; pulmonary morbidity

• Cosmetically good; minimal morbidity
• Technically difficult; risk of subtotal
*Maximal (sternotomy + cervical)
• Most complete resection
• Highest morbidity; two incisions; risk of
  recurrent laryngeal nerve injury.

• Cosmetically good; reduced incisional pain?
• Technically difficult; risk of subtotal
  thymectomy; post thoracoscopy neuralgia
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.
What are the steps to follow during pre-operative

1. Ensure optimum muscle power.correct
   oropharyngeal, bulbar and respiratory
   muscle weakness using the following regimen:
     a) anti-cholinesterase inhibitors
        (pyridostigmine, neostigmine).
     b) corticosteroids (prednisone,
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.
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
       a) chest x-ray
       b) arterial blood gases
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
3. 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
     c) 2D echocardiography when necessary

     d) stress test when necessary
4. 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
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.
Interaction with Other Drugs
Aminoglycoside    depress NM transmission.
antibiotics and

Beta blockers     exacerbate MG
Corticosteroids   exacerbate MG.
                  decrease dose requirements for
                  NDNMB in MG.
Procainamide ,    cause weakness in MG patient.
• 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.
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

    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.
• 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.
• 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
Maintain adequate post-operative pain control.
Avoid muscle relaxants and tranquilizing

Maintain adequate pulmonary toilet and
physical therapy

Avoid or use very cautiously drugs interfering
with neuro-muscular transmission
Anesthesia for thymectomy
What is the recommended anesthetic

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.
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.
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
• 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.
 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.
 -Depolarizing Neuromuscular Blocker

• MG patients show resistance to depolarizing

• MG patients are more likely to develop phase
  II block , particularly with repeated doses of
• 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
 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
  – Central respiratory depression may be a problem.
  – Use of short-acting opioids : more titratable.
    Remifentanil (elimination half-life:9.5min)
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 .
• 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.
-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.
• 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.
• 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.
• 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 .
• 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.
• What is the recommended post-operative

• Closely monitor at Post-Anesthesia Care Unit
  or Surgical Intensive Care Unit
  Respiratory support can be immediately

• 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
   -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.
• 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.
• If anticholinesterases and antimuscarinics has
  been used, muscarinic symptoms are absent,
  weakness and fasciculations predominate.

• Edrophonium test ,to differentiate this from
  myasthenic crisis.

• It is common practice to restart the medication
  immediately after thymectomy, but at a
  reduced dosage. This strategy avoids
  cholinergic crisis while preventing early
  postoperative myasthenic weakness.
• The importance of chest physiotherapy and
  general respiratory supportive care is obvious.

• To help deep breathing and coughing,
  incisional pain must be aggressively treated.
  Thoracic epidural analgesia and patient-
  controlled analgesia systems are helpful.

• Bronchial secretions, in part related to
  anticholinesterase medication, must be cleared.
Thymectomy for thymoma
• THYMOMA is the most common tumor of the
  anterosuperior mediastinum.

• Surgery remains the treatment of choice for
  thymomas. In the presence of severe central
  airway compression, anesthetic management
  can be a challenge.
• Various techniques have been proposed to deal
   with distal (tracheobronchial) airway
   obstruction including :
  -spontaneous ventilation
  -proximal tracheal intubation with distal jet
  -rigid bronchoscopy
  -prone, semierect, or lateral positioning.
• Béchard et al IN 2004 reported anesthetic and
  postoperative respiratory complications
  between 7% -20% and 18%, respectively, in
  pediatric patients with airway compromise.

• They defined the higher-risk patients as those
  with preoperative cardiorespiratory signs and
  symptoms as orthopnea, stridor, cyanosis,
  jugular venous distension, or SVC syndrome.

• combined obstructive and restrictive patterns
  on pulmonary group of patients.
• Shamberger et al,1995 suggested that general
  anesthesia should be avoided in children with -
  50% tracheal area obstruction.

• They postulated that adults may tolerate severe
  tracheal compression better than children.
• Loss of airway control with ventilatory failure
   often occurs on induction of general anesthesia
   with muscle paralysis due to:
  (1) reduction of lung volumes to a 500 to 1,500

 (2) bronchial smooth muscle relaxation leading
  to greater airway compression by tumor.

 (3) spontaneous diaphragmatic excursions lost,
  reducing normal transpleural pressure
  gradient (which keeps the airway open).
• institution of CPB has been suggested since
  acute airway obstruction puts the patient at
  unnecessary risk.

• Peripheral venoarterial CPB has the benefit of
  technical simplicity and quick setup.
• To preserve a normal transpulmonary pressure
  and maintain airway tone/patency (especially of
  the airway distal to the endotracheal tube), the
  maintainance of spontaneous respiration, even
  after tracheal intubation has been chosen.

• It allows assessment of the adequacy of the
  patient’s ventilation, which gave the confidence
  to remove CPB-support and reverse
  anticoagulation before proceeding to complete
• The use of peripheral CPB was chosen for 2
  (1) the imaging evidence of significant major
   airway obstruction with significant symptoms
   during her earlier biopsy.

 (2) the suspicion of tumor invasion into
  adjacent great vessels and the heart.
• Induction with the inhalation anesthetic while
  maintaining spontaneous respiration is
  achieved .

• Once the anesthesiologist is satisfied with the
  adequacy of mechanical ventilation and muscle
  paralysis,positive pressure ventilation is
  commenced with weaning off CPB, protamine
  reversal, and decannulation.

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