59. Myasthenia Gravis
Definition
Myasthenia gravis is an acquired autoimmune disorder of neuromuscular function marked by fatigue and exhaustion of the muscular system. Fluctuations in severity of muscular atrophy accompany periods of increased or decreased activity.
Incidence
Myasthenia gravis is not very common. It is estimated to occur at a rate of 2:1,000,000.
Etiology
Myasthenia gravis is caused by the presence of antibodies against acetylcholine receptors at the neuromuscular junction of skeletal muscles; 80% to 90% of myasthenia gravis patients have antibodies against acetylcholine receptors. Tolerance to acetylcholine receptors by the immune system is somehow lost, but the mechanism is not clear. Myasthenia gravis is considered to be a B-cell–mediated disease process; however, T-cells’ contribution to the process is becoming increasingly more evident. T-cell immunity is dominated by the thymus, and myasthenia gravis patients frequently have thymic hyperplasia, thymoma, or other thymus abnormalities.
Signs and Symptoms
• Acute respiratory failure
• Aspiration
• Difficulty chewing
• Difficulty swallowing
• Horizontal smile
• Hyperthyroidism
• Lupus
• Mask-like facies
• Nasal regurgitation of food and liquids
• Ophthalmoplegia
• Proptosis (exophthalmos)
• Ptosis
• Rheumatoid arthritis
• Scleroderma
Myasthenia Gravis Foundation of America Clinical Classifications
Class I
• Any ocular muscle weakness
• May have weakness of eye closure
• All other muscle strength is normal
Class II
• Mild weakness affecting other than ocular muscles
• May have ocular muscle weakness of any severity
Class IIa
• Predominately affecting limb or axial muscles or both
• May also have lesser involvement of oropharyngeal muscles
Class IIb
• Predominately affecting oropharyngeal or respiratory muscles or both
• May also have lesser or equal involvement of limb or axial muscles or both
Class III
• Moderate weakness affecting other than ocular muscles
• May also have ocular muscle weakness of any severity
Class IIIa
• Predominately affecting limb or axial muscles or both
• May also have lesser involvement of oropharyngeal muscles
Class IIIb
• Predominately affects oropharyngeal or respiratory muscles or both
• May also have lesser or equal involvement of limb or axial muscles or both
Class IV
• Predominately affects limb and/or axial muscles
• May also have lesser involvement of oropharyngeal muscles
Class IVb
• Predominantely affects oropharyngeal or respiratory muscles or both
• May also have lesser involvement of oropharyngeal muscles
• Use of a feeding tube without intubation
Class V
• Defined by intubation, with or without ventilation, except when used during routine postoperative management
• Use of a feeding tube with intubation
Medical Management
Currently no rigorous treatment trials have been reported and there is no consensus regarding treatment regimens. Initiation and/or alteration of treatment regimens must take into account disease severity, distribution of affected muscles, and rapidity of progression. Acetylcholinesterase inhibitors and immunomodulation are stalwarts in treating myasthenia gravis. Plasmapheresis and thymectomy are nontraditional immunomodulation therapies that have been employed.
Plasma exchange is an effective therapy before surgery or as an effective short-term management response to an acute exacerbation of the disease. The improvement in strength is helpful in reducing postoperative recovery time and may contribute to reduction of the length of ventilatory assistance. Muscle weakness is improved days after treatment initiation, but the improvement lasts only 6 to 8 weeks. Plasma exchange can be used as a long-term treatment for the patient who has not responded to other treatment regimens. The primary limitation of plasma exchange has been the difficulty of gaining intravenous access, but hypotension and coagulation derangements are also possible. Central venous access should be obtained for the patient receiving plasma exchange treatments.
Surgical intervention in the form of thymectomy is a very important option for myasthenia gravis patients. Some experts advocate this option as the first-line therapeutic intervention, particularly for patients with generalized myasthenia gravis and those with thymoma. Despite the absence of controlled trials to investigate the efficacy of thymectomy, this intervention has become the de facto standard of care for patients with thymoma or for those from 10 to 55 years of age with generalized myasthenia gravis. Disease remission may result from thymectomy, typically in younger patients who have been affected for only a short time, those with hyperplastic thymus, and those with high antibody titers. The frequency of remission increases over time; 7 to 10 years post-surgery, 40% to 60% of all thymectomy patients experience remission.
Drugs that Can Exacerbate Myasthenia Gravis Symptoms
• Antibiotics (aminoglycosides, ciprofloxacin, erythromycin, ampicillin)
• Anticholinergics (such as trihexyphenidyl)
• β-adrenergic blocking agents (propranolol, oxprenolol)
• Chloroquine
• Lithium
• Magnesium
• Prednisone
• Procainamide
• Quinidine
• Timolol (Blocadren)
• Verapamil
Complications
• Aspiration pneumonia
• Avascular necrosis
• Cataracts
• Dysphagia
• Fungal infections (systemic)
• Gastritis
• Hyperglycemia
• Lymphoproliferative malignancies
• Osteoporosis
• Peptic ulcer disease
• Pneumocystis jiroveci pneumonia
• Respiratory failure
• Teratogenic fetal effects
• Tuberculosis
• Weight gain
Anesthesia Implications
Immunomodulation requires renewed attention to antisepsis from the anesthetist. As a result of immunomodulation therapy, the patient may be more susceptible to opportunistic infection(s) and the anesthetist is involved in potentially hazardous aspects of antigen introduction: intravenous access and endotracheal intubation.
As part of immunomodulation therapy, corticosteroids are frequently incorporated into the treatment regimen. If steroids are a part of the patient’s treatment regimen, a perioperative stress dose of steroid will be needed.
Muscular weakness is a critical factor for the anesthetist to consider. The patient with myasthenia gravis is exquisitely sensitive to nondepolarizing muscle relaxants. For surgical procedures that require relaxation, the smallest effective dose should be administered. Minimizing the dose will increase the potential effectiveness of reversal medication if it is needed. The anesthetist is cautioned that ulnar nerve stimulation may demonstrate deceptively greater muscle strength than the patient actually has, and additional criteria should be employed for assessing the return of adequate muscle strength to allow for extubation. Even with these alterations, the anesthetist and the patient must recognize the very real possibility of prolonged effects from the muscle relaxants and all parties (patient, family, anesthetist, and surgeon) should be prepared for the potential need for postoperative ventilatory support. Postoperative ventilatory support is often continued via tracheal intubation with mechanical ventilation for a period of time to allow the patient to “naturally” regain the requisite muscle strength. However, even after regaining sufficient muscle strength for extubation, the patient with myasthenia gravis may succumb to fatigue and require re-intubation.
Intubation, at any time, of the patient with myasthenia gravis does not necessarily require administration of muscle relaxants. In addition to being extremely sensitive to nondepolarizing relaxants, the patient is resistant to the depolarizing muscle relaxants, such as succinylcholine. The response to a dose of succinylcholine is unpredictable. The patient with myasthenia gravis is prone to develop a Phase II block, even at the reduced succinylcholine dose of 0.5 mg/kg, and recovery from the Phase II block is a slow process. In contrast, it may be difficult to pharmacologically produce muscle relaxation because of the patient’s anticholinesterase therapy. Chronic anticholinesterase therapy also produces other effects, such as potentiation of vagal responses, reduced metabolism of ester-type local anesthetics, and increased duration and efficacy of narcotics. Because ester-type local anesthetics are not easily metabolized by patients with myasthenia gravis, this class of local agents may be more toxic for them than amide-type local anesthetics. Postoperative resumption of anticholinesterase therapy must be based on the outcome of the edrophonium test. Dosage requirements for anticholinesterase medications change, particularly during the postoperative period.
