Anesthesia For Patient With Myasthenia Gravis

Neuromuscular disorders has been classified into those affecting the central nervous system (both intracranially and at the spinalcord level),peripheral nerve leisons, disorders of neuromuscular leisons (Azar 1984).

Patients affected by any of these disorders commonly have such a significant degree of muscle wasting that they develop a marked decrease in respiratory reserve. Its not surprising therefore that such patient frequenly respond to many of the commonly used anesthetic drugs such for example as intrvenous agents ,analgesic and sedative, all of which may produce marked respiratory depression with respiratory arrest.

Detailed respiratory monitoring is therefore essential,not only preoperatively if the patients is breathing spontanously but also into the post operative period when respiratory failure from exhaustion is a constant treat.Patient with neuromusclular disorder may also be abnormally sensitive to neuro muscular blocking agents.

It is obligatory that if such drugs are to be used neuromucular function is monitored both during anesthesia and into the post operative period.

It will of course, be realized that these diseases may remain undiagnosed until anesthesia is administered. Unexpected sensitivity especially to neuromuscular blocking agents may then be encountered and prolonged artificial ventilation may be necessary.

The problem encountered when such patients need prolonged treatment in the intensive care unit. One of these diseases is myasthenia gravis,autoimmun disease,resulting from the production of antibodies against the acetylcholine receptors(AchR) of the neuroendplate(post junctional membrane).

This disease affect about 1 in 20.000 population, there a proponderance of female 2:1 in patients below 50 years of age but over 50 years its equally distributed between the sexes,the peak onset for women is between the age of 20 to 30 years whereas the peak onset for men is the sixt to seven decade. But the incidence in those under 10 years is low, about 10% of all cases.

It is remain unknown what trigers this auto immune disease. However a genetic predisposition exist as well as an ascociation with other autoimmune disordes such as systemic lupus erythematosus,thyrotoxicosis,polymyositis and rheumatoid arthritis.

The disease is frequently associated with morphologic abnormalities of the thymus gland such a thymoma and thymic hyperplasia. Hyperplasia occurs more often in younger patients, and thymoma are more common in those over 30 years old.

Infact 15% to 20% of patients with mysthenia gravis (MG) have thymomas especially older men. Antibodies to the AchR protein are present in the sera of aproximately 85% of patients with MG. The mayority of these antibodies are of the immuno globulin G class and bind to the primary immuno genics region of the alpha sub unit of AchR.These antibodies reduced the number of active receptors by functional block of the receptor,by increasing the rate of receptor degradation or by a complememediated lysis of post synaptic membrane.

The level of circulating receptor antibody does not correlated well with the clinical severity of the disease.Furthermore those patients with MG who fail to demonstrate AchR antibodies may posses different antibodies that bind to other yet to be identified endplate determinant. A clinical hallmark of this disease is that repeated or persistent activity of a muscle group leads to

exhaustion of its contractile power and rest at least partially restores the power.

The onset of the disease is usually insidious and progression is marked by periods of exacerbate and remissions.It is usually presents with weakness of the cranial muscles especially the ocular and oropharyngeal groups.The musles of the eyes,face,jaws,throat and neck are affected first. Patient may complain of drooping eyelids and diplopia and altered facial mobility and expressions.

Weakness of pharyngeal and laryngeal muscles result in dysarthria,dysphagia and difficult with clearing secretions.Typically this painless weakness spreads at varying rate through out the body to involve not only the limbs (proximal muscles being more involved than distal ones) but also eventually the muscle of respiration.

The various stages of the disease process has been classified by Osserman and Jenkins (1971)

1. Ocular only

2. a  Generalized, mild muscle weakness

    b  Generalized moderately severe weakness

3. Acute fulminating presentation.

          

Weakness tends to increase as the day progress and temporary increase in weakness have been reported with vaccination,menstruation,pregnancy and extreem of the temperatures. It should also be recognized that 15% to 20% of neonatus born to mothers with MG will exhibit transmyasthenia.This situation likely because of the passage of the AchR antibodies across placenta.

Diagnosis :

Severe cases are easily diagnosed but mild ones can be overlooked and may cause anesthetic difficulties.The diagnosis can frequently be made on basis of the history and presence of circulating antibodies. It is not uncommon that diagnosis of MG is made following administration of relaxants during an operation,causing a more severe and prolonged neuromuscular block than anticipated in a normal individual.In mild cases,confirmation may be required and the patient is treated with short acting anticholine esterase(edrophonium or tensilon) or challenged with a small dose of neuro muscular blocking drugs.

The anesthesiologist is frequently called upon to assist in the performance of the test because of familiarity with the drugs and his ability to monitor neuromuscular transmission and cope with respiratory embrassment shoul this occur.

Edrophonium in 10 mg iv dose will inhibit the action of cholinesterase so that the acetylcholine released at the endplate will be less rapidly hydrolized,facilitating neuromuscular transmission in the myasthenic individual.

Patiens already treated with an anticholinesterase may be weak due to an overly high concentration of these drugs.To differentiate such a cholinergic crisis from myasthenic crisis,a test with a short acting anticholinesterase such as edrophonium is preferable.

As an alternative, small dose of curare (0,5-1,0) mg can be given at five minutes intervals to a total dose of 4 mg, causing a marked decrease in the twitch,the grip strength,and the vital capacity in the patient suffering myasthenia.These change should be carefully measured and recorded in the patient's chart.In 1970 Foldes described a technique in which a much smaller dose of curare 0,2 mg is used in an arm to which a torniquet is applied.Muscle strength can then be studied without much danger of respiratory embrassment.

TREATMENT

Treatment consist of (1) rest (2) medication with oral anti cholinesterase (neostigmine pyridostigmied),veratum alkaloids(germane diacetate),(3) symptomatic relief (ventilatory support),(4) thymectomi (5) plasma pharesis involves the use an automatic cell separator to remove circulating antibodies or immune complexes from the blood.

This form treatment has frequently been proven succesful also when patients failed to respond to drugs and thymectomi.In some institution this technique is used to improve the patient's muscular strength prior to a thymectomi.

Many years ago was only perfomed as soon as the diagnosis is established in the hope that progress of the disease will be halted.

Certainly morbidity will be less when the respiratory musculature is less deranged and the lungs have not been damaged by frequent aspiration.

PRE OPERATIVE PREPARATION :

Perioperative care of the patients with MG begins with adequate preoperative preparation The anesthesiologist must posses a clear picture of the patient's condition.

The severity of myasthenia and involvement of respiratory and bulbar muscle must be assessed. Pulmonary function studies should be performed to identify those with little respiratory reserve and to help predict the need for post operative respiratory support.

Measurement of vital capacity,the maximum negative force of inspiration and the maximum expiratory flow rate,help give a picture of the mechanical capabilities of respiratory musculature.

Knowledge of the arterial PO2 (PaO2)  can be helpful in estimation of functional alveolar tissue, while measurement of the PaCO2 and pH, estimates the integrity of the entire pulmonary apparatus.

The medical control of myasthenic patient will determine the need for preoperative preparation. That is if the patient is responding well to the use of pyridostigmine,no further therapy may be needed. However if the response is poor,preoperative plasma pharesis should be considered.

For example, it has been suggested that patient with severe form of the disease treated with prethymectomy plasma exchange required less mechanical ventilation and less time in the intensive care unit post operatively.There is a wide variation of opinion among anesthesioplogist as to the continuation or otherwise of anti cholinesterase therapy immediately prior to surgery.

If therapy is stopped before surgery, the patient is often very weak on presentation in the anesthetic room and may indeed be distressed by this weakness.In such circumtances the need for a neuro muscular blocking is reduced.

By the end of surgery however,the patient is even weaker,and large doses of anti cholinesterase may then be indicated with increased risk of a cholinergic crisis. It is probably preferable,therefore to continue therapy until induction of anaesthesia even if this necessitates a large dose of neuromuscular blocking agents.

Sedatives as premedication should be minimal,and opiate and barbiturate shoud be avoided. Steroid is required for those receiving it regularly.and serum postssium should be estimated as hypo kalimia aggravates myasthenia.

A nasogatric tube may well be in place for swallowing problem.

ANESTHETIC  MANAGEMENT

The chief concern is to ensure adequate respiration both during and after operation while special difficulties to be borne in mind are muscular weakness and bronchial secretion from neostigmin.

In operation that do not involve the chest or upper abdomen the anaesthesiologist may choose a regional technique.Regional analgesia which does not depress respiration e.g.intra or extra dural block to Th10 may be suitable.Epidural anaesthesia has been said to exacerbate the symptoms of MG It has been suggested that this in either due to the local anesthetic agents inhibiting presynaptic release of acetylcholine or because of the toxicity of ester local anaesthetic agents on the diseased muscle. Theoritically large doses of ester type local anaesthetic shoud be avoided.In those myasthenic patients receiving anti cholinesterase therapy because plasma cholinesterase activity is decreased and toxicity may be enhanced.There are reports however of the succesful use of lignocaine(lidocaine) in epidural analgesia for Caesarian Section in MG patient (Coaldrake and Livingstone,1983),although emphasis is laid on the need to reduce the dose of local anesthetics agents to prevent excessive motor block.

Tetracaine may be used for spinal anaesthesia because only small dose are needed. In general anaesthesia anaesthetic agents which are rapidly eliminated are the drugs of choice.

In elective minor surgery procedure,spontanous or assisted ventilation is usually adequate. The drugs affecting the neuromusculr junction should be avoided or used in greatly reduced quantities since the response of the neuromuscular junction is unpredictable. Because of the decreased number of functional AchR in MG patients exhibit a decrease response to depolarizing agents and a marked sensitivity to non depolarizing relaxants.

This abnormal response is seen even in patients who have localized ocular myasthenia and in those in remission.A large dose of succinylcholine may be needed for intubation,however anticholinesterase used preoperatively can reduce plasma cholinesterase activity causing a delayed hydrolysis of succinyl choline and potentiation of neuromuscular blockade.

Although some patients are resistant to depolarizing block but some patients with small dose of succinylcholine may likewise may induce prolonged paralysis. The non depolarizing drugs must be used extreme caution in MG.

The intermediate acting drugs atracurium and vecuronium can be used but it must be emphasized that despite their rapid elemination both exhibit prolonged effects in those with MG composed with control.

Response to muscle relaxants must be carefully titrated to clinical effect with the use of nerve stimulator,so that the anaesthesiologist can assure himself at the end operation neuromuscular transmission will not be depressed.

The clinicians must be aware that certain drugs especially aminoglycoside antibiotics, potent inhaled agents and magnesium can potentiate the neuromuscular blocking actions of muscle relaxant.

POST OPERATIVE CARE

Those myasthenic patients who have no respiratory difficulties preoperatively may have lost enough: of their ventilatory reserve through operation to experience after thymectomi.

With the current tendency to operate at a very early stage of the disease extubation in the operating room first hours following operation can be undertaken,provided the patient clearly shows that he can maintain his blood gases without ventilatory assistance and without undue effort.

The patient's vital capacity should measure more than 10 ml/kg.If the patient able to demonstrate a vital capacity greater than 15 ml/kg,extubation in the operating room is safe. The preoperative functional state of the patient's lung is also important wether post operative IPV will probably necessary.

Four risk factors for need for postoperative ventilation have been identified :

1. Duration of MG longer than 6 years

2. History of chronic respiratory disease,other than respiratory dysfunction
    related to MG.

3. Dose of pyridostigmine > 750 mg/day

4. Preoperative vital capacity < 2,9 L

Following thymectomi,anticholinesterase therapy should not be immediately resumed in those patient who require respiratory support.

The increase of patient's strength is not important at this time and the increase of secretion by the use of these drugs makes the patient more uncomfortable,leads to more suctioning and causes more pulmonary complications.

It has been reported that an increase sensitivity to anticholinergic agents in this periode may lead to a cholinergic crisis (a decrease of neuromuscular transmission causes by anticholinesterase overdose).

Patient should be started a lower doses than their preoperative needs and the medication should be increased slowly as needed.Analgesic drugs should be administered carefully in order to provide optimum analgesia and minimum respiratory depression.Other factors such as nutrional state,age and mental status are also important.

Many of MG patients are well aware of seriousness of their disease and many even have experienced periods of near suffocation.Patients are depressed apprehensive,frighten and even occasionally suicidal. Inspite of all monitor used in intensive care unit,his fear subsided only a competent and delicated nurse was at his bedside.

SUMMARY :

MG is autoimmune disease resulting from the production of antibodies against the acetylcholine receptors (AchR) of motor endplate.It is more common in women than in man and usually develops between the age of 20 and 50.

The diagnosis of MG can frequently be made on the basis of history and the presence of circulating antibodies.Treatment of MG consist of (1) rest (2) medication with oral anticholinesterase or steroid(3) symptomatic relief (ventilatory support) (4) thymectomi and (5) plasmapharesis.

In anaesthesing a patient suffering from MG the anaesthesiologist must extremely careful in his use of drugs affecting the neuromuscular junction.Perioperative care of  the patient with MG begins with adequate preoperative preparation.

Post operative ventilatory support may be needed when there are four risk factors : 

a. Duration Of MG longer than 6 years.

b. History of chronic respiratory disease other than respiratory disfunction related to MG.

c. Dose of pyridostigmine >750 mg/...?

d. Preoperative vital capacity < 2,9 L.

The depressed mental status of the patient must also be considered.

REFERENCES :

1. Kareis JH;Myasthenia Gravis, in Ravis MG,Problems in Anesthesia,1st ed, Little Brown and Company,Boston,1981.

2. Leisure GS,Phillips LH ;Anesthesia for the patient with neurologic disaease,in Stone DJ Sperry Johnson JO et all The Neuroanaesthesia hand book, Mosby Year Book, London.

3.Hunter JM ;Anaesthesia for patient with neuromuscular disorders,in NunJF,Unting JE,Brown, Text book of General Anaesthesia,5th edition Buttorwouths London,Boston 1989.

4.Atkinsons RS,Rushman GB. Medical diseases influencing anesthesia,in textbook of Synopsis 10th ed,PG.Asian Economy Edition,Singapore,Hongkong, New Delhi 1988.

Posted in: Anesthesia, Myasthenia Gravis, Neuroanesthesia