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Anesthetic Implications of Myasthenia Gravis

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Anesthetic Implications of Myasthenia Gravis Anesthetic Implications of Myasthenia Gravis MARK ABEL, M.D.1, AND JAMES B. EISENKRAFT, M.D.2 Abstract Myasthenia gravis is a disease of great significance to the anesthesiologist, because it affects the neuro- muscular junction. Many patients with this condition are treated by surgical thymectomy, using tech- niques developed by Mount Sinai physicians, including Dr. Paul Kirschner, Dr. Alan E. Kark, and the late Dr. Angelos E. Papatestas. The authors review the anesthetic considerations in the management of patients with myasthenia gravis who are undergoing thymectomy and other surgical procedures. Key Words: Myasthenia gravis, anesthesia, thymectomy. Epidemiology and Pathophysiology velop respiratory failure. Thymoma is present in 10 –15% of patients with MG (5). In a now MYA S T H E N I A G R AV I S (MG) is an autoimmune classic paper, Osserman and Genkins, both disease characterized by weakness and fatiga- physicians at The Mount Sinai Hospital, pub- bility of skeletal muscles, with improvement lished a clinical classification of myasthenia following rest. It may be localized to specific gravis that is still in widespread use (6). muscle groups or it may be generalized. The in- The diagnosis of MG can be confirmed by cidence is 50–142 cases per million population several tests. The anticholinesterase test is pos- (1). MG is caused by a decrease in the numbers itive if strength improves with inhibition of of postsynaptic acetylcholine receptors at the cholinesterase. When cholinesterase is inhib- neuromuscular junction (2), which decreases ited, more acetylcholine is available to interact the capacity of the neuromuscular end-plate to with the decreased number of postsynaptic re- transmit the nerve signal. Initially, in response ceptors, increasing the likelihood of adequate to a stimulus resulting in depolarization, acetyl- end-plate depolarization. Edrophonium (Te n- choline is released presynaptically. In MG, the s i l o n®) is usually administered intravenously in number of activated postsynaptic receptors may small (2– 8 mg) doses for this test. This test be insufficient to trigger a muscle action poten- was introduced and popularized by Dr. Osser- tial (3). Further, with repeated stimulation, the man (7). Electromyography is also used in the decline in release of acetylcholine correlates diagnosis of myasthenia. Repetitive stimula- with the characteristic fatigability (4). tion of a peripheral motor nerve leads to de- creasing responses by the innervated muscle in P resentation and Diagnosis a patient with MG. The presence of anti-acetyl- choline antibodies in the serum, as detected by The characteristic presentation of MG is r a d i o i m m u n o a s s a y, is diagnostic of MG. Such fatigability of voluntary muscles. Most com- antibodies may not be detectable, however, in m o n l y, the eyelids and extraocular muscles are all patients with mild symptoms at presentation. involved. Bulbar involvement may be mani- fested as difficulty in chewing and swallowing. Tre a t m e n t Eighty-five percent of myasthenic patients go on to develop generalized weakness; some de- Treatment of MG may be medical or surg i- cal, utilizing one of three approaches: anti- cholinesterases (medical), immune suppression (medical), or thymectomy (surg i c a l ) . 1Assistant Professor of Anesthesiology and 2Professor of An e s t h e - Improving neuromuscular transmission by si o l o g y , Mount Sinai School of Medicine, New York, NY. means of anticholinesterase agents is the most Address correspondence to Mark Abel, M.D., Department of An e s t h e s i o l o g y , Box 1010, Mount Sinai School of Medicine, One common approach. Pyridostigmine (Mestinon) East 100th Street, New York, NY 10 0 2 9 - 6 5 7 4 . in a dose of up to 120 mg p.o. every 3 hours is 32 THE MOUNTSINAI JOURNALOF MEDICINE January/March 2002 used because it is tolerated well orally, with few If a thymoma presents an anterior mediasti- muscarinic side effects, and has a relatively nal mass, intrathoracic airway or vascular ob- long duration of action. Pyridostigmine 30 mg struction may occur upon the induction of anes- orally is equivalent to 1 mg intravenously or in- thesia. Flow-volume loops may be indicated t r a m u s c u l a r l y. p r e o p e r a t i v e l y. Maximal inspiratory and expi- Immune suppression is directed at prevent- ratory flow-volume loops obtained with the pa- ing or attenuating the destruction of acetyl- tient in the supine and upright positions will choline receptors at the motor end plate (8). measure the extent of the respiratory impair- Corticosteroids, which cause immune suppres- ment as well as whether the impairment is fixed sion, will improve the condition of most myas- or dynamic. thenics (9). Those who do not respond or who The preoperative management of the myas- cannot tolerate the side effects may respond to thenic patient will be influenced by the surg i c a l azathioprine 2.5– 3.5 mg/kg. Cyclosporine has procedure and the preferences of the surg e o n been used in patients with MG (10) and com- and the anesthesiologist. Some choose to omit pares favorably with azathioprine (11 ) . anticholinesterase on the morning of surg e r y, to For patients with severe bulbar symptoms decrease the need for muscle relaxants (21), or respiratory compromise (myasthenic crisis), whereas others continue its use for psychologi- plasmapheresis is used (12). Significant im- cal support of the patient. If the patient is provement occurs over days, with decreased de- poorly controlled, a course of plasmapheresis pendence on ventilatory support (13). The pre- may be of benefit in the preoperative period sumed mechanism is the removal of antibodies, (22). The steroid-dependent patient will require allowing receptors to proliferate. Immune perioperative coverage. globulin given intravenously has been used to Anxiolytic, sedative, and opioid premedica- treat myasthenic crises when plasmapheresis tions are rarely given to patients who may have cannot be used. Its use has been associated little respiratory reserve. If the patient has pri- with good short-term improvement (14). marily ocular symptoms, a small dose of benzo- Thymectomy is used to treat MG, but the diazepine is acceptable. mechanism of its action remains speculative. Antibody titers decrease with clinical improve- Response to Anesthetic Drugs ment (15). Suggested mechanisms include re- moval of antigenic stimulus by the removal of Nondepolarizing Neuro m u s c u l a r B l o c k e rs myoid cells or alterations in immune regulation by removal of the thymus. For an up-to-date Neuromuscular blocking drugs act by inter- history of surgery of the thymus gland, as well rupting neuromuscular transmission at the level as speculation on the future, the recent review of the nicotinic acetylcholine receptors at the by Kirschner (16) is recommended reading. motor end plate. Their mode of action can be classified as antagonist (nondepolarizing) or Anesthesia Considerations — Pre o p e r a t i v e agonist (depolarizing), both producing block- Evaluation and Pre p a r a t i o n ade (23). The myasthenic patient is typically sensitive to nondepolarizing neuromuscular Preoperative evaluation of the MG patient blockers. The use of a small dose for priming includes review of the severity of the patient’s or defasciculation is not appropriate, because it disease and the treatment regimen. Specific at- may result in loss of airway protection or in res- tention should be paid to voluntary and respira- piratory distress. Sensitivity to nondepolariz- tory muscle strength. The patient’s ability to ing agents has been described in patients with protect and maintain a patent airway postopera- minimal disease (i.e., ocular symptoms only) tively may be compromised if any bulbar in- (24), in those in apparent remission (25), or volvement exists preoperatively. The ability to those with subclinical undiagnosed myasthenia cough and clear secretions may be compromised ( 2 6 ) . as well. Respiratory muscle strength can be Long-acting muscle relaxants such as d- quantified by pulmonary function tests (nega- tubocurarine, pancuronium, pipecuronium, and tive inspiratory pressure and forced vital capac- doxacurium, are best avoided in these patients. ity). These tests may be necessary as a refer- Intermediate and short-acting nondepolarizing ence to determine the optimal conditions for ex- agents can be used with careful monitoring of tubation postoperatively as well as the need for neuromuscular transmission, preferably with postoperative mechanical ventilation (17, 18). electromyogram (EMG) or mechanomyogram Vol. 69 Nos. 1 & 2 ANESTHESIAAND MYASTHENIAGRAVIS—ABEL 33 (MMG), which measure the evoked electrical or cular block by agonist action. The ED9 5 of suc- mechanical responses following electrical stim- cinylcholine in MG patients is 2.6 times that in ulation of a peripheral motor nerve. Stimuli can non-myasthenic patients (0.8 mg/kg vs. 0.3 be delivered singly (0.1 Hz or one every 10 sec- mg/kg) (34). The dose of succinylcholine used onds; 1 Hz or one per second), or in trains-of- for rapid airway control in normal patients, 1.5 four (TOF) stimuli (2 Hz) at 10-second inter- mg/kg, is approximately five times the ED9 5 i n vals. In the absence of a neuromuscular block, MG. A dose of 1.5 –2.0 mg/kg should be ade- a control response is obtained. This control quate for most myasthenics, for rapid sequence “twitch” is designated Tc. In the absence of a intubation (34). A case report of a myasthenic neuromuscular block, all responses should be of patient in complete remission showed a normal equal magnitude.
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