A 38-year-old woman with a 5-year history of myasthenia gravis (MG) Osserman and Genkins grade IIB presented for transcervical thymectomy. Her medications were pyridostigmine, 240 mg, azathioprine, 100 mg, and prednisone, 15 mg per day in divided doses. She was also taking omeprazole 20 mg per day for reflux esophagitis. Spirometry revealed a vital capacity of 60% predicted and forced expiratory volume in 1 second/forced vital capacity of 80%. After placement of standard monitors and while the patient was breathing 100% oxygen, rapid-sequence induction with cricoid pressure was performed using propofol, 2 mg/kg, and succinylcholine, 1.5 mg/kg. The trachea was intubated uneventfully. Anesthesia was maintained with oxygen, air, fentanyl, and desflurane as required. Ventilation was controlled throughout the procedure. Neuromuscular monitoring with a peripheral nerve stimulator was initiated, and cisatracurium, 0.05 mg/kg, was administered with resulting loss of twitch response to peripheral nerve stimulation. The surgery proceeded uneventfully and lasted 2 hours. Anesthetic agents were discontinued, and the patient demonstrated four equal twitch responses to train-of-four (TOF) stimulation. Neostigmine, 0.06 mg/kg, and glycopyrrolate, 0.01 mg/kg, were administered. When the patient was awake and responded to commands, her trachea was extubated. Soon after extubation, the patient became dyspneic.
What is myasthenia gravis?
MG is an autoimmune disorder of the neuromuscular junction, the function of which is routinely altered in modern anesthesia practice. Typically, MG manifests as a fluctuating, painless weakness and easy fatigability of voluntary muscles. Weakness resolves with rest. Slow, insidious onset is common, and the condition is associated with relapses and remissions. The incidence of MG is approximately 1 in 30,000 adults and 1 in 200,000 children and adolescents. These figures may underestimate the true incidence because mild cases in elderly adults are commonly misdiagnosed. Peak incidence occurs in the third decade of life for women and fifth decade for men, but any age may be affected.
In MG, antibodies are produced to the acetylcholine (nicotinic) receptor of the neuromuscular junction. Consequently, patients with MG have 70% to 80% fewer usable postsynaptic acetylcholine receptors at the end plates of affected muscles, fewer folds in synaptic clefts, and widened synaptic clefts. The amount of presynaptic acetylcholine released is normal or increased. In a person with a normal number of acetylcholine receptors, only 25% to 30% of the receptors are required for normal neuromuscular transmission; this is termed the “margin of safety” in neuromuscular transmission. In patients with MG, the margin of safety is decreased.
How is myasthenia gravis diagnosed, and how is it classified?
The diagnosis of MG is suspected from the patient’s history and confirmed by clinical, electrophysiologic, immunologic, and pharmacologic testing. Although any muscle group may be affected, the most common onset is ocular, with ptosis or diplopia. If the disease remains localized to the eyes for 2 years, there is a low likelihood of progression to generalized MG. Involvement of bulbar musculature predisposes to difficulty breathing and swallowing.
Patients with MG cannot sustain or repeat muscle contractions. Electromyography (EMG) studies can highlight this feature when a motor nerve is stimulated three times per second (3 Hz). A decrement of response of at least 10% by the fifth stimulus is usually seen in patients with MG. Although this is the most specific nerve test for MG, it can be performed only on certain muscles, which may not be the muscles affected in the individual patient.
The edrophonium (Tensilon) test may help to differentiate MG when responses to EMG studies are equivocal. An intravenous dose (2 to 10 mg) of the acetylcholinesterase inhibitor edrophonium may elicit improvement in the strength of patients with MG because it inhibits the degradation of acetylcholine. In normal patients, no improvement in strength is seen.
If testing is still equivocal, a regional curare test may be employed. In this test, an arterial tourniquet is applied to isolate the limb and limit the drug’s systemic action. EMG is performed before and after administration of very small doses of curare (0.2 mg) into a forearm. Patients with MG show a marked decrease in response to repeated stimulation. In equivocal cases, antibodies to acetylcholine receptors may be detectable; however, antibody titers do not correlate with severity of disease. When MG is diagnosed, the Osserman and Genkins classification system is commonly used to describe the severity of disease ( Table 24-1 ).
|Grade||Name||Description||Testing and Prognosis|
|I||Ocular||Involvement of ocular muscles only |
Diplopia and ptosis
|Electrophysiologic testing of other musculature negative|
|IA||Ocular + peripheral||Involvement of ocular muscles |
No clinical symptoms in peripheral musculature
|Electrophysiologic testing of other musculature positive|
|IIA||Mild generalized||Involvement of skeletal or bulbar musculature |
No respiratory involvement
|Good response to drug therapy|
|IIB||Moderate generalized||More severe involvement of skeletal and bulbar muscles |
Dysarthria, dysphagia, difficulty chewing without respiratory involvement
|Fair response to drug therapy|
|III||Acute fulminating||Rapid onset of severe bulbar and skeletal weakness with respiratory involvement||Poor response to therapy |
Low mortality rate
|IV||Late severe||Severe MG developing >2 years after onset of symptoms||Poor response to therapy |
What are the treatment alternatives for a patient with myasthenia gravis?
The mainstay of treatment for MG is to increase the amount of acetylcholine available at the neuromuscular junction, increasing the likelihood of agonist-receptor interaction and successful neuromuscular transmission. Acetylcholinesterase inhibitors such as neostigmine (Prostigmin), edrophonium, and pyridostigmine (Mestinon) have been used for this purpose since 1934. Physostigmine is not used because it crosses the blood-brain barrier producing central nervous system symptoms. Because of its longer duration of action and fewer muscarinic side effects, pyridostigmine has the best treatment profile within the drug class. Dosage requirements can vary from day to day, and patients frequently learn to titrate amounts accordingly. Overdosage can cause cholinergic crisis, and underdosage can cause myasthenic crisis.
Treatment may also be directed at immunomodulation to decrease the amount of circulating antibodies. In the short-term, immunomodulation is managed with steroids; long-term therapy involves other immunosuppressive agents, such as azathioprine, cyclophosphamide, cyclosporine, methotrexate, rituximab, and tacrolimus. Steroids can provide clinical improvement in 80% of patients; however, initiation of steroid therapy often exacerbates symptoms because of direct inhibitory effects on neuromuscular transmission. In addition, prolonged therapy may lead to side effects such as osteoporosis, hypertension, and peptic ulcers.
Plasmapheresis or plasma exchange produces transient but dramatic improvement in clinical symptoms in 45% of patients. Improvement may last days to weeks after the procedure. This treatment is reserved for severe MG. Of significance to the anesthesiologist is that plasmapheresis can decrease levels of plasma cholinesterase, resulting in prolonged effects of drugs, such as succinylcholine, that are metabolized by this enzyme.
Many patients with MG have abnormalities of the thymus gland. Imaging (computed tomography or magnetic resonance imaging) may help confirm the presence of an abnormal thymus. Thymectomy provides significant long-term immunomodulation and improvement in most patients. It is considered the treatment of choice for most patients with MG; the exception is patients with Osserman and Genkins class I MG. Response to thymectomy is best when the procedure is performed within the first 3 years after diagnosis. Clinical outcome is equivalent whether the procedure is performed via video-assisted thoracoscopy or via a median sternotomy.