Management of Myasthenic Syndromes for Patients Undergoing Anaesthesia and Intensive Care

This article focuses on the aspects of anaesthetic and intensive care management for the myasthenic syndromes. Information regarding pathophysiology, diagnosis, clinical features and chronic management of these conditions are outside the scope of this article.

Patients with any of the myasthenic syndromes, may present to an acute hospital in 3 ways:

1. On established control treatment regimes presenting for an elective surgical procedure (including thymectomy) or presenting for emergency surgery
2. Patients who decompensate following surgery (myasthenic or cholinergic crises)
3. Emergency medical presentation (myasthenic crisis) necessitating intensive care therapy

Myasthenia gravis (MG) is a postsynaptic disorder of the motor plate (nicotinic) receptors of the skeletal muscle. It is purely an autoimmune disorder in which there are circulating acetylcholine receptor (Ach-R) or muscle specific tyrosine receptor (MuSk-R) antibodies, which result in skeletal muscle fatigue. The precise clinical features are described elsewhere in the myaware series. It may be associated with other autoimmune diseases e.g. rheumatoid arthritis, thyroiditis, systemic lupus erythromatosis.

Lambert-Eaton myasthenic syndrome (LEMS) is a disorder affecting presynaptic voltage gated calcium channels at the motor end plate. It is most commonly associated with para-neoplastic diseases e.g. small cell lung carcinoma.

Consideration for the Anesthetist

All myasthenic conditions are extremely sensitive to neuromuscular blocking agents (MIB). These drugs are required for intubation, ventilation and muscle relaxation needed to facilitate neurological, thoracic or abdominal surgery, e.g. brain and spine surgery, lung resection, oesophageal resections, major aortic surgery, major stomach and bowel resection surgery.

Procedures on peripheral parts of the body e.g. limbs, pelvis, skin, neck, face, may be facilitated by local anaesthetic blockade and light anaesthesia / sedation, however the anaesthetist must be careful not to use local anaesthetic techniques which might impair respiratory function (e.g. interscalene block for shoulder surgery, high thoracic epidurals, high dose lignocaine or prilocaine).

Preparation for Surgery Requiring the Use of Neuromuscular Blockers (NNB)

Where possible for planned / elective procedures advice / involvement of a neurologist is desirable. Patients should be operated on in the morning, preferably first on the list (as their muscle function is at its strongest).

Where possible, any elective procedure can be deferred until treatment is optimised by the neurologist and drugs associated with exacerbation of MG stopped or modified.

Patients Listed for Surgery Should Receive the Following:

Ongoing anticholinesterase therapy upon arrival in the anaesthetic room. If unable to take internal medication (e.g. for emergency surgery or for elective oesophageal or stomach surgery), then pyridostigmine can be given IV as 1 / 30th of current oral dose if required). Be aware, however, that pyridostigmine can make some types of myasthenia worse. Alternatives are IV neostigmine. Steroids need to be supplemented as IV hydrocortisone or dexamethasone if the patient is currently on >20mg / day for 3 weeks or more. Ongoing immunosuppressant treatments can be stopped the night before surgery (e.g. azathioprine, mycophenolate, cyclosporine, tracolimus).

Where intubation of the airway is required in the emergency setting, an awake fiberoptic intubation under local anaesthesia is preferable. NMB use for emergency intubation is associated with need for postoperative ventilation (e.g. suxamethonium and rocuronium in LEMS, rocuronium in MG).

Intra-operative management of NMB agents can be difficult in terms of predicting the dose, duration and the use of reversal agents (which are anticholinesterases e.g neostigmine). The latter can precipitate a cholinergic crisis. A new reversal agent, Sugammadex, appears to be safe and effective for some NMB agents (rocuronium and vecuronium).

It is advisable to use neuromuscular monitoring (relaxagraph or train of four-TOF) to assess muscle function before and after reversal agent is given (where a TOF <82% of maximum - it is unlikely the patient will be adequately reversed and therefore will need postoperative ventilation).

Concomitant intra-operative drugs can lessen the success of reversal.

Antiobiotics (erythromycin, clarithromycin, gentamicin, vancomycin, ciprofloxacin, clindamycin)

Cardiovascular Drugs (atenolol, metoprolol, labetalol, propranolol, magnesium, verapamil)

Anaesthetic Agents (Lignocaine, prilocaine, bupivacaine, isoflurane, halothane)

Antiepileptic / Antipsychotic Drugs (haloperidol, phenytoin)

Factors Associated with Post-Operative Ventilation / Need for Intensive Care / Post-Operative Complications Are:

• Co-existing respiratory disease (chronic obstructive airways disease)
• Previous myasthenic crisis
• A low forced vital capacity (FVC) < 2.1 litres
• Existing features of bulbar symptoms (dysphagia, poor phonation)
• Concomitant active infection
• Post-operative thymectomy patients
• Predicted intra-operative blood loss > 1000mls
• Concomitant administration of intra-operative drugs listed above
• TOF count<82% of maximum

Post-Operative Care

If any factors above are met, then it is not advised to extubate (remove the endotracheal tube) in recovery - and the patient should be transferred to ITU for ongoing ventilation.

If the patient is to be extubated then it is advisable to perform thorough suctioning and lavage of the tracheal-bronchial tree prior to removal of the endotracheal tube. The patient should be nursed in recovery (post anaesthetic care unit) for > 2 hours to ensure all residual anaesthetic agents are clear, and reversal agents are still effective. It is particularly important that the use of reversal agents does not lead to a cholinergic crisis within the first 30 minutes. Patients should then be nursed on a high dependency unit (HDU) preferably attached to the ITU.

Obstetric Patients

These can be a very high risk group for complications, but in essence:

• Those in labour who need an epidural, should receive a very low concentration local anaesthetic (preferably 0.1% bupivacaine or 0.2% ropivacaine with a liquid soluble opiate (fentanyl or diamorphine) as a low volume infusion
• Those in need of an instrumental delivery can receive a top up of 0.25% bupivacaine, but special attention is required to ensure the block height doesn't go above T10 and affect the respiratory muscles
• Those in need of Caesarean section cannot safely tolerate the high block levels required and should have a general anaesthetic and post-operative HDU or ITU care

Post-Operative ITU Care

It is important to continue anticholinesterase drugs (pryidostigmine and normal pre-operative doses. Also immunosuppressant agents should be restarted with neurology advice. Drugs associated with potential exacerbations must be stopped. Vigilance to high incidence of super imposed infections and appropriate antibiotic therapy and use of antithrombotic drugs (enoxaparin) to reduce the risk of deep vein thrombosis and coronary events).

Patients must receive frequent tracheo-bronchial lavage prior to extubation. Criteria for extubation are a successful spontaneous breathing trial of > 30 minuted associated with tidal volumes of > 7mls / kg and vital capacity of > 15mls / kg plus a peak inspiratory pressure of > than -25cm H2O (i.e. -26cm to -35cm).

Myasthenic Crisis

It occurs in 2-3% of all MG patients but is the first presentation in 20% of cases. In a first presentation, it is important to differentiate it from other peripheral neurological emergencies below:

• Cholinergic crisis (normally existing MG patients)
• Guilliain-Barré syndrome
• Severe depressive psychosis
• Syringomvelia
• Acute botulism
• Polio
• Acute hypothyroid
• Mitochondrial myopathies

In those with MG / LEMS, precipitating factors can be:

• Stress (post-operative surgery)
• Hypothermia (extreme physical activity, bright sunlight)
• Menstruation
• Infection
• Drug induced (some of which have been listed but also eye drops including timolol, tropicamide and betaxolol

ITU Management

Any patient in which lung funtion testing shows a vital capacity of < 20mls / kg (ideal body weight) with a reduction in peak inspiratory pressure of less than - 25cm H2O should be referred to ITU.

Criteria for intubation and ventilation include:

• PaCO2 > 6KPa associated with a respiratory rate > 20 / min
• Bulbar weakness with poor cough and aspiration on chest X-ray
• Any evidence of cholinergic crisis (often due to overdosing of anticholinesterase or inappropriate reversal following anaesthesia with NMBs) - weakness and excessive SLUDGE (salivation, lacrimation, urination, defecation, gastrointestinal distress and emesis)

Patient needs emergency intubation and ventilation. Exclude precipitants including known:

• Stop pyridostigmine or other anticholinesterase drugs
• Send following tests - complement and immunoglobulin levels, AChR and MuSK antibody levels, creatinine kinase and thyroid function tests

If clear evidence of myasthenia crisis, then start the following:

• Plasma exchange of IgC selective plasmapheresis (3-5 litre exchanges per day for 10-14 days) - or pooled human immunoglobulin (except in IgA disease) at 400mg / kg / day for 5 days
• Steroids at 60-80mg / day of prednisolone for 2 weeks (note that this may worsen MG within the first 5 days)
• Liaise with neurologist regarding long-term immunosuppression
• Liaise with thoracic surgeons if thymic mass is present

If clear evidence of cholinergic crisis then start the following:

• Glycopyrollate - 1mg 4 hourly
• Hyoscine
• Loperamide

For patients with MG or LEMS, the treatment options are similar but patients with LEMS are less likely to respond.

Criteria for extubation are a successful spontaneous breathing trial of > 30 minutes associated with tidal volumes of > 7mls / kg and vital capacity of > 15mls / kg plus a peak inspiratory pressure of > than -25cm H2O (i.e. -26cm to -35cm).

However, there is a need for re-intubation in 27% of patients, so careful consideration needs to be taken early in the ITU stay as to timing of tracheostomy (especially in the presence of a thymic mass).

For all these patients despite treatment above there is 5% mortality, even when managed on ITU (higher in LEMS) with an average of 2 weeks need for intubation and ventilation. Such patients are at high risk of developing super-imposed infection (lungs / kidney / colon) as well as thrombo-embolic phenomena (pulmonary emboli) and heart failure (takotsuba cardiomyopathy).

Dr Stephen Digby BSc MBBS FRCA FICCM
Consultant in anaesthesia and intensive care management

Advice from Fellow Practitioners