Neuromascular Council Consensus Statement

NEUROMUSCULAR NEUROMUSCULAR COUNCIL CONSENSUS COUNCIL CONSENSUS

STATEMENTSTATEMENT

THYMECTOMY FOR THYMECTOMY FOR NONTHYMOMATOUS NONTHYMOMATOUS

AUTOIMMUNEAUTOIMMUNEMYASTHENIA GRAVIS MYASTHENIA GRAVIS

PATIENTSPATIENTS

IntroductionIntroduction

Through the years many neurologists have Through the years many neurologists have favored the use of thymectomy in the favored the use of thymectomy in the management of patients with nonthymomatous management of patients with nonthymomatous autoimmune myasthenia gravis (MG). This autoimmune myasthenia gravis (MG). This wide acceptance is based largely upon case wide acceptance is based largely upon case series and retrospective studies which have series and retrospective studies which have suggested that thymectomy may be beneficial. suggested that thymectomy may be beneficial. However, many of these studies have shown However, many of these studies have shown variable results. Moreover, the absence of variable results. Moreover, the absence of controlled, prospective trials casts some doubt controlled, prospective trials casts some doubt regarding effectiveness of the procedure in this regarding effectiveness of the procedure in this group of patients. Thus, until the results of an group of patients. Thus, until the results of an ongoing international, prospective, single blind ongoing international, prospective, single blind randomized trial controlling for medical randomized trial controlling for medical therapy become available, the use of therapy become available, the use of thymectomy in this situation remains thymectomy in this situation remains controversial.controversial.

In the local medical centers where In the local medical centers where thymectomy is being performed, no standard thymectomy is being performed, no standard guidelines in the selection of patients and guidelines in the selection of patients and the pre- and post-operative management the pre- and post-operative management have been created. This necessitates the have been created. This necessitates the formulation of such guidelines.formulation of such guidelines.

ObjectivesObjectives

General ObjectiveGeneral Objective

The Neuromuscular Council of the The Neuromuscular Council of the Philippine Neurological Association aims Philippine Neurological Association aims to improve outcomes for MG patients by to improve outcomes for MG patients by providing the initial framework for providing the initial framework for decision-making for neurologists with decision-making for neurologists with regard to the patient diagnosed with regard to the patient diagnosed with nonthymomatous autoimmune MG who is nonthymomatous autoimmune MG who is a candidate for thymectomy.a candidate for thymectomy.

Specific ObjectiveSpecific Objective

To develop a combined evidence- and To develop a combined evidence- and consensus-based practice parameter to consensus-based practice parameter to guide neurologists in managing patients guide neurologists in managing patients diagnosed with nonthymomatous diagnosed with nonthymomatous autoimmune myasthenia gravis who can autoimmune myasthenia gravis who can be candidates for thymectomy.be candidates for thymectomy.

MethodologyMethodology

Group CompositionGroup Composition

The working group is composed of the members The working group is composed of the members of the Neuromuscular Council of the PNA.of the Neuromuscular Council of the PNA.

Dr. Lina Renales

Dr. Rosalia Teleg

Dr. Valmarie Estrada

Dr. Darwin Dasig

Dr. Emmanuel Eduardo

Dr. Alejandro Diaz

Dr. Raymond Rosales

Dr. Jose Paciano Reyes

Dr. Ludwig Damian

Dr. Marita Dantes

Consensus ProcessConsensus Process

The initial draft of the consensus The initial draft of the consensus statement was a synthesis of the survey, statement was a synthesis of the survey, identification of the key clinical issues, identification of the key clinical issues, output of literature search using Medline output of literature search using Medline and the local registry and academic and the local registry and academic deliberation by the working group over the deliberation by the working group over the identified key issues. Deliberation included identified key issues. Deliberation included appraisal of the literature in terms of validity appraisal of the literature in terms of validity and applicability, preparation of evidence-and applicability, preparation of evidence-based summaries and development of based summaries and development of judgments by consensus. This is to be judgments by consensus. This is to be followed by presentation of the statements in followed by presentation of the statements in a public forum composed of the PNA fellows. a public forum composed of the PNA fellows.

Disclaimer:Disclaimer:

The assessment and recommendations The assessment and recommendations provided herein represent the best provided herein represent the best professional judgment of the working group professional judgment of the working group at this time, based on research data gathered at this time, based on research data gathered and on expertise currently available. The and on expertise currently available. The conclusions and recommendations will be conclusions and recommendations will be regularly assessed as new information regularly assessed as new information becomes available. The consensus statement becomes available. The consensus statement is intended to be an educational guideline is intended to be an educational guideline and is therefore neither rigidly prescriptive and is therefore neither rigidly prescriptive nor restrictive.nor restrictive.

Key Clinical Key Clinical Issues AddressedIssues Addressed

1.1. Should thymectomy for nonthymomatous Should thymectomy for nonthymomatous myasthenia gravis be recommended?myasthenia gravis be recommended?

2.2. What is the clinical profile of What is the clinical profile of nonthymomatous autoimmune MG nonthymomatous autoimmune MG patients likely to benefit from patients likely to benefit from thymectomy?thymectomy?

3.3. When is the ideal time to perform When is the ideal time to perform thymectomy?thymectomy?

4.4. What is the preferred thymectomy What is the preferred thymectomy technique to use?technique to use?

5.5. What is the recommended pre-operative What is the recommended pre-operative management? management?

6.6. What is the recommended post-operative What is the recommended post-operative management?management?

Consensus Consensus ProperProper

QUESTION 1:QUESTION 1:

Should thymectomy for Should thymectomy for nonthymomatous autoimmune nonthymomatous autoimmune

myasthenia gravis be recommended?myasthenia gravis be recommended?

A. Consensus StatementA. Consensus StatementPractice RecommendationPractice Recommendation

For patients with nonthymomatous For patients with nonthymomatous autoimmune MG, thymectomy is autoimmune MG, thymectomy is recommended as an recommended as an option option to increase the to increase the probability of remission or improvement probability of remission or improvement (Level 2 evidence). (Level 2 evidence).

Research RecommendationResearch RecommendationThere is a need to conduct a well-There is a need to conduct a well-

designed, prospective, controlled study to designed, prospective, controlled study to evaluate clinical effectiveness of evaluate clinical effectiveness of thymectomy in nonthymomatous, thymectomy in nonthymomatous, autoimmune myasthenia gravis patients autoimmune myasthenia gravis patients that utilize comparison with standardized that utilize comparison with standardized medical therapy and well-defined medical therapy and well-defined evaluation standards.evaluation standards.

B. Summary of EvidenceB. Summary of Evidence

To address the uncertainty of the To address the uncertainty of the usefulness of thymectomy in usefulness of thymectomy in nonthymomatous autoimmune MG because nonthymomatous autoimmune MG because of the lack of prospective and controlled of the lack of prospective and controlled studies, the working group utilized the studies, the working group utilized the systematic review done by the American systematic review done by the American Academy of Neurology.1 Their review of 28 Academy of Neurology.1 Their review of 28 articles (Class II evidence 2) published from articles (Class II evidence 2) published from 1953 to 1998 describing outcome in 21 MG 1953 to 1998 describing outcome in 21 MG cohorts revealed the following cohorts revealed the following observations:observations:

1.1. Positive associations in most studies Positive associations in most studies between thymectomy and MG remission between thymectomy and MG remission and improvement with median rates of and improvement with median rates of 2.1 for medication-free remission, 1.6 for 2.1 for medication-free remission, 1.6 for asymptomatic group and 1.7 for asymptomatic group and 1.7 for improvement;improvement;

2.2. Confounding differences in baseline Confounding differences in baseline characteristics of prognostic importance characteristics of prognostic importance between thymectomy and between thymectomy and nonthymectomy groups in all studies;nonthymectomy groups in all studies;

3.3. Persistent positive associations between Persistent positive associations between thymectomy and improved outcomes thymectomy and improved outcomes after controlling for single confounding after controlling for single confounding variables such as age, gender and variables such as age, gender and severity of MG;severity of MG;

4.4. Conflicting associations between Conflicting associations between thymectomy and improved MG outcomes thymectomy and improved MG outcomes in studies controlling for multiple in studies controlling for multiple confounding variables simultaneously.confounding variables simultaneously.

They concluded that it cannot be They concluded that it cannot be determined from available studies determined from available studies whether the observed association whether the observed association between thymectomy and improved MG between thymectomy and improved MG outcome was a result of thymectomy outcome was a result of thymectomy benefit or was merely a result of multiple benefit or was merely a result of multiple differences in baseline characteristics. differences in baseline characteristics. Thus, the benefit of thymectomy in Thus, the benefit of thymectomy in nonthymomatous autoimmune MG has not nonthymomatous autoimmune MG has not been established conclusively. been established conclusively.


What is the clinical profile of What is the clinical profile of nonthymomatous autoimmune MG nonthymomatous autoimmune MG patients most likely to benefit from patients most likely to benefit from

thymectomy?thymectomy?

A. Consensus StatementA. Consensus Statement

Practice RecommendationPractice Recommendation

The candidate most likely to benefit is The candidate most likely to benefit is the patient with all of the following the patient with all of the following attributes (Level 2 evidence): attributes (Level 2 evidence): generalized MGgeneralized MG age between puberty and 60 years andage between puberty and 60 years and positive titers for anti-Acetylcholine positive titers for anti-Acetylcholine

Receptor Antibody (anti-AChR Ab) when Receptor Antibody (anti-AChR Ab) when applicableapplicable

female genderfemale gender

Research RecommendationResearch RecommendationThere is a need to conduct a well-There is a need to conduct a well-

designed prospective, controlled study to designed prospective, controlled study to evaluate clinical outcome after evaluate clinical outcome after thymectomy with respect to the disease thymectomy with respect to the disease variables (e.g. grade or severity of the variables (e.g. grade or severity of the illness, age of the patient, gender, illness, age of the patient, gender, duration of the disease, etc.), treating duration of the disease, etc.), treating these variables singly or in combination.these variables singly or in combination.

B. Summary of EvidenceB. Summary of Evidence1.1. GenderGender

Women have been reported to have a better Women have been reported to have a better outcome than men after thymectomyoutcome than men after thymectomy

2.2. AgeAge There is general consensus that patients with There is general consensus that patients with

generalized MG between puberty and 60 years generalized MG between puberty and 60 years will benefit from thymectomy.will benefit from thymectomy.

Most MG experts advocate cutoff ages ranging Most MG experts advocate cutoff ages ranging between 50 to 70 years with median at 60 years.between 50 to 70 years with median at 60 years.

Thymectomy has been performed with favorable Thymectomy has been performed with favorable results in childhood. Procedure, however, results in childhood. Procedure, however, remains controversial in younger children with remains controversial in younger children with ages ranging from 1 year to puberty.ages ranging from 1 year to puberty.

3.3. Clinical SeverityClinical Severity Patient subgroup analysis in one studyPatient subgroup analysis in one study

indicated that only those patients with MG with indicated that only those patients with MG with moderate weakness or greater (Osserman 2B3 / moderate weakness or greater (Osserman 2B3 / MGFNA4 ) showed significant improvement MGFNA4 ) showed significant improvement after thymectomy compared with control after thymectomy compared with control subjects. Results, however, were confounded subjects. Results, however, were confounded by baseline patient differences across groups.by baseline patient differences across groups.

The studies reviewed did not include patients The studies reviewed did not include patients with pure ocular MG.with pure ocular MG.

Severe patients who underwent thymectomy Severe patients who underwent thymectomy had better prognosis compared with severe had better prognosis compared with severe patients who did not.patients who did not.

4.4. Duration of DiseaseDuration of Disease No data have been gathered as yet regarding No data have been gathered as yet regarding measurement of outcome after controlling for measurement of outcome after controlling for single confounding variable like duration of single confounding variable like duration of disease (whether within 1-2 years from onset or disease (whether within 1-2 years from onset or beyond 2 years from onset).beyond 2 years from onset).

No conclusive data likewise are available No conclusive data likewise are available associating improved MG outcome with associating improved MG outcome with thymectomy after controlling for multiple thymectomy after controlling for multiple

confounding variables.confounding variables.


When is the ideal time to When is the ideal time to perform thymectomy? perform thymectomy?



Thymectomy is best performed Thymectomy is best performed within 1 to 2 years from the time of within 1 to 2 years from the time of diagnosis diagnosis provided that provided that the patient has the patient has achieved:achieved: optimal muscle strength and optimal muscle strength and optimal medical conditionoptimal medical condition adequate cardio-pulmonary functions adequate cardio-pulmonary functions

(Level 2 evidence)(Level 2 evidence)

Research RecommendationResearch Recommendation

There is a need to conduct a well-There is a need to conduct a well-designed prospective, controlled study to designed prospective, controlled study to evaluate clinical outcome after evaluate clinical outcome after thymectomy with respect to the timing of thymectomy with respect to the timing of surgery.surgery.


Some authors suggested that benefits Some authors suggested that benefits from thymectomy were achieved more from thymectomy were achieved more readily the earlier the surgery was done, readily the earlier the surgery was done, with larger remission rates per unit time with larger remission rates per unit time (Class III evidence)(Class III evidence). . However, it has been However, it has been postulated that this may be solely due to postulated that this may be solely due to non-linear rate at which MG patients non-linear rate at which MG patients achieve remission after diagnosis. This achieve remission after diagnosis. This means that for a given duration of time, means that for a given duration of time, MG patients are more likely to remit earlier MG patients are more likely to remit earlier than later.than later.


What is the preferred What is the preferred thymectomy technique to use?thymectomy technique to use?

A. Consensus StatementA. Consensus StatementPractice RecommendationPractice Recommendation

Properly performed total thymectomy Properly performed total thymectomy using the Extended Transsternal Approach using the Extended Transsternal Approach may provide the greatest resection with low may provide the greatest resection with low morbidity and less risk for recurrent laryngeal morbidity and less risk for recurrent laryngeal nerve injury (Level 2 evidence).nerve injury (Level 2 evidence).

Research RecommendationResearch Recommendation

There is a need to conduct a well-There is a need to conduct a well-designed prospective, controlled study to designed prospective, controlled study to evaluate clinical outcome after thymectomy evaluate clinical outcome after thymectomy with respect to the different thymectomy with respect to the different thymectomy technique.technique.


The report of the Quality Standards The report of the Quality Standards Committee of the American Academy of Committee of the American Academy of Neurology1 concluded that the outcome Neurology1 concluded that the outcome comparisons between uncontrolled studies do comparisons between uncontrolled studies do not provide conclusive evidence of the not provide conclusive evidence of the superiority of one technique over another. superiority of one technique over another. This was due to the numerous confounding This was due to the numerous confounding differences in patients’ baseline differences in patients’ baseline characteristics and new confounders characteristics and new confounders (institutional, geographic and historical (institutional, geographic and historical differences).differences).

Likewise, controlled trials reviewed Likewise, controlled trials reviewed failed to provide convincing evidences that failed to provide convincing evidences that one technique was superior, again due to one technique was superior, again due to the confounding differences and the confounding differences and inconsistent results. Moreover, operative inconsistent results. Moreover, operative techniques employed were either not techniques employed were either not identified or limited to standard identified or limited to standard transsternal and basic transcervical transsternal and basic transcervical thymectomy. thymectomy.

The review of the retrospective studies3 The review of the retrospective studies3 that wasthat was published after the AAN Guidelines published after the AAN Guidelines publication concluded that the studies had publication concluded that the studies had conflicting results and had many confounding conflicting results and had many confounding variables such as patient population, variables such as patient population, accompanying therapy, details of evaluation, accompanying therapy, details of evaluation, extreme variability and unpredictability of extreme variability and unpredictability of MG, variability of selection of patients for MG, variability of selection of patients for thymectomy and immunesuppressives drugs thymectomy and immunesuppressives drugs after surgery. The need for properly designed after surgery. The need for properly designed prospective trials or a non-randomized prospective trials or a non-randomized prospective study of two or more techniques prospective study of two or more techniques remains.remains.

In a separate article4 In a separate article4 ,,Jaretzski had Jaretzski had written that the more complete the thymic written that the more complete the thymic resection, the better the outcome.resection, the better the outcome.

A retrospective trial comparing the late A retrospective trial comparing the late results of basic transsternal and extended results of basic transsternal and extended transsternal thymectomies5transsternal thymectomies5 revealed that revealed that complete remission rates were significantly complete remission rates were significantly higher in the extended group at 1, 2, 3 and 4 higher in the extended group at 1, 2, 3 and 4 years follow-up (Level 2 evidence). Negative years follow-up (Level 2 evidence). Negative results (no improvement, deterioration or results (no improvement, deterioration or death from MG) were significantly lower in the death from MG) were significantly lower in the extended thymectomy group. The difference extended thymectomy group. The difference was postulated to be due to the removal of was postulated to be due to the removal of ectopic foci of thymic tissue from the neck and ectopic foci of thymic tissue from the neck and mediastinum.mediastinum.

Mantegazza et.al. performed a Mantegazza et.al. performed a prospective, uncontrolled trial comparing prospective, uncontrolled trial comparing video-assisted thoracoscopic extended video-assisted thoracoscopic extended thymectomy (VATET) and T3-B operative thymectomy (VATET) and T3-B operative techniques6techniques6 and concluded that VATET and concluded that VATET seems to be effective in inducing complete seems to be effective in inducing complete stable remission similar to T-3B TS approach stable remission similar to T-3B TS approach (Level _ evidence). VATET had the advantage (Level _ evidence). VATET had the advantage of being easier to perform and having lower of being easier to perform and having lower morbidity and negligible esthetic sequelae.morbidity and negligible esthetic sequelae.


What is the recommended pre-What is the recommended pre-operative management?operative management?


The objective of a pre-operative The objective of a pre-operative management is to ensure that there will be management is to ensure that there will be careful selectioncareful selection of patients for thymectomy of patients for thymectomy to optimize its long term benefits. The patients to optimize its long term benefits. The patients must be in optimum medical condition prior to must be in optimum medical condition prior to surgery to avoid or minimize intraoperative surgery to avoid or minimize intraoperative and post-operative complications.and post-operative complications.

Management in the peri-operative period Management in the peri-operative period requires a concerted effort among the requires a concerted effort among the neurologist, thoracic surgeon, pulmonologist neurologist, thoracic surgeon, pulmonologist and other internists, the anesthesiologist and and other internists, the anesthesiologist and the physiatrist.the physiatrist.

Practice RecommendationPractice Recommendation5.1 5.1 What are the steps to follow What are the steps to follow

during pre-operative management?during pre-operative management?1. Perform a thorough neurologic evaluation 1. Perform a thorough neurologic evaluation

and clearance: Ensure that the patient has and clearance: Ensure that the patient has optimum muscle power. When appropriate, optimum muscle power. When appropriate, correct oropharyngeal, bulbar and correct oropharyngeal, bulbar and respiratory muscle weakness using the respiratory muscle weakness using the following regimen:following regimen:

a)a) anti-cholinesterase inhibitors anti-cholinesterase inhibitors (pyridostigmine, neostigmine) and/or (pyridostigmine, neostigmine) and/or any of the following:any of the following:

b)b) corticosteroids (prednisone, corticosteroids (prednisone, prednisolone)prednisolone)

c) other immunosuppressants when these c) other immunosuppressants when these become necessary. Use of these, become necessary. Use of these, however, may require several weeks to however, may require several weeks to a several months before optimum a several months before optimum therapeutic benefit is obtained. therapeutic benefit is obtained.

d)d) plasmapheresis or intravenous immune-plasmapheresis or intravenous immune-globulin, when applicable, in patients globulin, when applicable, in patients with moderate to severe bulbar and with moderate to severe bulbar and respiratory muscle weakness or in respiratory muscle weakness or in patients with a high titer of anti-patients with a high titer of anti-Acetylcholine Receptor antibodies.Acetylcholine Receptor antibodies.

5.15.1

2. Acquire adequate pulmonary evaluation 2. Acquire adequate pulmonary evaluation and clearance to assure presence of and clearance to assure presence of patent airways, optimum respiratory patent airways, optimum respiratory muscle power, adequate clearing of muscle power, adequate clearing of secretions and absence of respiratory secretions and absence of respiratory infection.The following pre-operative tests infection.The following pre-operative tests are recommended:are recommended:

a) chest x-raya) chest x-ray

b) arterial blood gases b) arterial blood gases

c) pulmonary function test (including VC, c) pulmonary function test (including VC, FEV, MEF, flow-volume loop) and FEV, MEF, flow-volume loop) and exercise testing (with 6-8 hours off exercise testing (with 6-8 hours off anticholinesterase inhibitor e.g. anticholinesterase inhibitor e.g. Mestinon)Mestinon)

d) sputum G/S, C/S when necessaryd) sputum G/S, C/S when necessary

e) chest CT scan when necessarye) chest CT scan when necessaryf) perfusion studies when necessaryf) perfusion studies when necessary

5.15.1

3.3. Perform cardiac evaluation as follows:Perform cardiac evaluation as follows:

a) basic tests: ECG, chest x-ray;a) basic tests: ECG, chest x-ray;

b) complete cardiology evaluation b) complete cardiology evaluation and and clearance if clearance if

- the patient is 40 years old or - the patient is 40 years old or above above

- if patient has history of - if patient has history of ischemic ischemic heart disease or heart disease or other cardiac problems or other cardiac problems or risks for developing cardiac problems.risks for developing cardiac problems.

c) 2D echocardiography when c) 2D echocardiography when necessary necessary

d) stress test when necessaryd) stress test when necessary

e) nuclear medical tests when e) nuclear medical tests when necessary necessary

5.15.1

4.4. Search for and adequately treat Search for and adequately treat concomitant medical conditions:concomitant medical conditions:

a) Infectiona) Infectionb)b) Disorders associated with MG. Do the Disorders associated with MG. Do the

following tests:following tests:- ESR- ESR- thyroid function tests- thyroid function tests- blood sugar- blood sugar- ANA- ANA- rheumatoid factor- rheumatoid factor

c) Disturbance in nutrition, fluids and c) Disturbance in nutrition, fluids and electrolytes electrolytes

5.15.1

5. Check CBC and bleeding parameters (CT, BT, 5. Check CBC and bleeding parameters (CT, BT, PT, PTT). PT, PTT).

6. Refer to Rehabilitation Medicine specialist to 6. Refer to Rehabilitation Medicine specialist to assure good pulmonary capacity and adequate assure good pulmonary capacity and adequate muscle tone. muscle tone.

7. Consider drug effects and drug interactions. 7. Consider drug effects and drug interactions. If the patient is on medications, ensure that If the patient is on medications, ensure that there are no side effects of these drugs or there are no side effects of these drugs or adverse drug reactions that may interfere with adverse drug reactions that may interfere with or complicate the intra- and post-operative or complicate the intra- and post-operative course of the patient course of the patient (Refer to Table on Drug (Refer to Table on Drug Effects and Interactions ).Effects and Interactions ).


5.25.2 What is the recommended What is the recommended anestheticanesthetic management? management?

1. Anesthesiologists must consider the 1. Anesthesiologists must consider the patient’s disease severity including:patient’s disease severity including:

- voluntary and respiratory muscle - voluntary and respiratory muscle strengthstrength

- ability to protect and maintain - ability to protect and maintain patent airway patent airway post-operatively post-operatively

- the type of surgical procedure and - the type of surgical procedure and the the surgeons’ preferences surgeons’ preferences

- patient’s ongoing medication (e.g. - patient’s ongoing medication (e.g. Mestinon and Mestinon and steroids). steroids).

5.25.2

2. For pre-operative medications:2. For pre-operative medications:

Generally, anxiolytics, sedatives Generally, anxiolytics, sedatives and and opioids are rarely given to opioids are rarely given to patients with little patients with little respiratory reserve. respiratory reserve.

Small dose benzodiazepines, Small dose benzodiazepines, when when necessary, may be given to necessary, may be given to patients with good patients with good respiratory reserve.respiratory reserve.

5.25.2

3. Choice of anesthetic agents:3. Choice of anesthetic agents:

The anesthesiologist must confer with the The anesthesiologist must confer with the neurologist and the surgeon and neurologist and the surgeon and

other specialists other specialists when needed.when needed.

There are several anesthetic agents that There are several anesthetic agents that can be used can be used (see Table on Anesthetic (see Table on Anesthetic Agents).Agents).

There is There is nono anesthetic technique that is anesthetic technique that is superior to superior to others. Choice depends on others. Choice depends on preference of the preference of the doctors. These doctors. These techniques have included:techniques have included:

a.a. Avoidance of muscle Avoidance of muscle relaxants and use of relaxants and use of potent inhaled potent inhaled anesthetics both for anesthetics both for facilitating tracheal facilitating tracheal intubation and intubation and providing relaxation providing relaxation for surgery.for surgery.

b.b. Titration of small Titration of small doses of doses of intermediate acting intermediate acting relaxants to the relaxants to the evoked EMG.evoked EMG.

c.c. Use of total Use of total intravenous intravenous anesthesia (TIVA).anesthesia (TIVA).

d.d. Use of local or Use of local or regional anesthetic regional anesthetic techniques.techniques.

e.e. The decision The decision whether to reverse whether to reverse residual NM residual NM blockade at the end blockade at the end of surgery or to wait of surgery or to wait for spontaneous for spontaneous recovery and recovery and extubate when extubate when patient patient demonstrates demonstrates adequate adequate parameters for parameters for extubation remains extubation remains controversial.controversial.

5.25.2

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


5.35.3 Should pyridostigmine be Should pyridostigmine be continued or discontinued pre-continued or discontinued pre-operatively?operatively?

A. Consensus Statement A. Consensus Statement

Practice RecommendationPractice RecommendationPyridostigmine or other Pyridostigmine or other

anticholinesterase may be continued pre-anticholinesterase may be continued pre-operatively if the patient derives improved operatively if the patient derives improved muscle strength with its use. The following muscle strength with its use. The following guidelines are recommended:guidelines are recommended:

1. To allow a decrease in the blood level pre-1. To allow a decrease in the blood level pre-operatively, give pyridostigmine or anticholinesterase operatively, give pyridostigmine or anticholinesterase 4 to 6 hours pre-operatively. In this way, it will not 4 to 6 hours pre-operatively. In this way, it will not interfere with the anesthetic. Pyridostigmine may be interfere with the anesthetic. Pyridostigmine may be resumed post-operatively.resumed post-operatively.

2. Pyridostigmine may cause increase in oral and 2. Pyridostigmine may cause increase in oral and tracheal secretions especially in intubated patients. tracheal secretions especially in intubated patients. This can be titrated to avoid or minimize problems in This can be titrated to avoid or minimize problems in post-operative pulmonary toilet.post-operative pulmonary toilet.


Omitting pyridostigmine pre-Omitting pyridostigmine pre-operatively may reduce the need for operatively may reduce the need for muscle relaxant as well as lessen the muscle relaxant as well as lessen the effect of ester anesthetic agents. effect of ester anesthetic agents. However, the omission of the However, the omission of the pyridostigmine on the day of surgery pyridostigmine on the day of surgery predisposed myasthenic patients to the predisposed myasthenic patients to the possibility of respiratory discomfort and possibility of respiratory discomfort and sensitivity to vecuronium.7 (Class I sensitivity to vecuronium.7 (Class I evidence)evidence)


5.4 Should corticosteroids be continued 5.4 Should corticosteroids be continued or discontinued pre- and peri- or discontinued pre- and peri- operatively?operatively?



Steroids should be continued pre-Steroids should be continued pre-operatively in steroid-dependent patients.operatively in steroid-dependent patients.


Steroid-dependent patients have the Steroid-dependent patients have the possibility of developing post-operative possibility of developing post-operative deterioration or crisis so that they will deterioration or crisis so that they will require pre- and peri-operative coverage.8 require pre- and peri-operative coverage.8 (Level 2 evidence)(Level 2 evidence)

Steroids also decrease dose of non-Steroids also decrease dose of non-depolarizing relaxants to which depolarizing relaxants to which myasthenic patients are highly sensitive.myasthenic patients are highly sensitive.


What is the recommended post-What is the recommended post-operative management?operative management?



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

6.26.2 Predict as accurately as possible the Predict as accurately as possible the best time to extubate based on:best time to extubate based on:

- Pre-operative condition of the patient- Pre-operative condition of the patient

- Surgical technique used- Surgical technique used

6.26.2

- Residual anesthetic effect- Residual anesthetic effect

- Parameters for weaning include: - Parameters for weaning include: absence of crisis absence of crisis triggers, objective triggers, objective findings showing adequate findings showing adequate muscle muscle power, vital capacity > 10 ml/kg, negative power, vital capacity > 10 ml/kg, negative

inspiratory force > 20 cm water, inspiratory force > 20 cm water, positive positive expiratory force > 40 cm expiratory force > 40 cm water. water.


6.36.3 Predict as accurately as possible Predict as accurately as possible the need for post-operative the need for post-operative mechanical ventilation based on:mechanical ventilation based on:

- Pre-operative condition of the - Pre-operative condition of the patientpatient

- Surgical technique used- Surgical technique used

- Residual anesthetic effect- Residual anesthetic effect

- Parameters: Kaneda - Parameters: Kaneda 1995/Eisenkraft 1995/Eisenkraft 1986/or 1986/or Leventhal 1980Leventhal 1980


6.46.4 Maintain adequate post-operative pain Maintain adequate post-operative pain control. control.

Avoid muscle relaxants and tranquilizing Avoid muscle relaxants and tranquilizing drugs.drugs.

6.56.5 Maintain adequate pulmonary toilet Maintain adequate pulmonary toilet and physical therapyand physical therapy

6.66.6 Avoid or use very cautiously drugs Avoid or use very cautiously drugs interfering with neuro-muscular interfering with neuro-muscular transmission transmission (Refer to Table on Drugs Acting (Refer to Table on Drugs Acting on NM Junction))on NM Junction))


6.76.7 Determine the best time to resume Determine the best time to resume pyridostigmine/anticholinesterase and pyridostigmine/anticholinesterase and steroids/immunesuppressants and the steroids/immunesuppressants and the appropriate dose, considering that:appropriate dose, considering that:

- Anticholinesterases can keep muscle power - Anticholinesterases can keep muscle power at adequate levels. at adequate levels.

- Anticholinesterases can increase oral and - Anticholinesterases can increase oral and tracheal secretions. tracheal secretions.

- Steroid-dependent patients will need - Steroid-dependent patients will need immediate post-operative coverage. immediate post-operative coverage.

Thank you very Thank you very much!much!

Health & Medicine

Neuromascular Council Consensus Statement