Anesthesia for Thymectomy

Rami Wahba, M.D

Lecturer of Anesthesia

Ain Shams University

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.

 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
fatigability.
Thymectomy plays a central role in the
treatment of myasthenia gravis.

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.

 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 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.

 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

 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
fashion.

 Thymectomy: general principles

-Pre-operative
Medical stabilization of myasthenia
-Anaesthesia:
Avoid muscle relaxants.
-Operative:
Total thymectomy.
Avoid phrenic nerve injury.

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

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.

 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
*Sternotomy
Technically simple
Cosmetic concerns; pulmonary morbidity
*Transcervical
Cosmetically good; minimal morbidity
Technically difficult; risk of subtotal
thymectomy

*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

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

management?
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,
prednisolone)

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 immuneglobulin 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 recommended:
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 (FEF2575%) 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 problems.
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
electrolytes

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
antibiotics and
polymyxins

depress NM transmission.

Beta blockers

exacerbate MG

Corticosteroids

exacerbate MG.
decrease dose requirements for
NDNMB in MG.

Procainamide ,
phenytoin

cause weakness in MG patient.

 Should pyridostigmine be continued or

discontinued pre-operatively?

Pyridostigmine or other
anticholinesterase may be continued preoperatively if the patient derives
improved muscle strength with its use.

The following guidelines are recommended:

1. To allow a decrease in the blood level preoperatively, 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 postoperative 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 steroiddependent patients.
Steroid-dependent patients have the possibility of developing
post-operative deterioration or crisis so they will require preand peri-operative coverage.
Steroids also decrease dose of non-depolarizing relaxants.

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

Anesthesia for thymectomy

What is the recommended anesthetic management?
1. Anesthesiologists must consider the patients disease
severity including:
- voluntary and respiratory muscle strength
- ability to protect and maintain patent airway postoperatively
- the type of surgical procedure.
- patients 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
included:

 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

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

 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 muscle.
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 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

-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 overstimulationtwitching, 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
ventilation
-rigid bronchoscopy
-prone, semierect, or lateral positioning.

 Bchard 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 ml.

(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 patients
ventilation, which gave the confidence to remove
CPB-support and reverse anticoagulation before
proceeding to complete resection.

 The use of peripheral CPB was chosen for 2

reasons:
(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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