Myasthenia gravis is the most common disorder of neuromuscular transmission. The hallmark is a fluctuation of ocular, bulbar, limb, and respiratory muscle weakness, which results from T-cell antibody-mediated attack on the postsynaptic acetylcholine membrane receptor proteins. Approximately 12 percent to 16 percent of myasthenic patients experience a crisis, usually within two to three years of initial diagnosis. Crisis is more common in patients with a previous history of oropharyngeal weakness, thymoma, or crisis. (Postgrad Med 2000;107:211.)
Triggers of myasthenia gravis crisis include infections (30% to 40% of cases), aspiration (10% of cases [Ann N Y Acad Sci 1981;377:670]), physical and emotional stress, and changes in medications. In many cases (30% to 40%), no precipitant can be identified. (Postgrad Med 2000;107:211; Neurology 1997;48:1253.)
A differential diagnosis of myasthenia gravis crisis is more difficult in patients who have never had one before, especially in the ED where information is typically limited. The differential diagnosis of acute or subacute respiratory failure is extensive, but myopathies, neuropathies, botulism, organophosphate toxicity, acetylcholinesterase inhibitor overdose, Eaton-Lambert syndrome, and central neurologic lesions can mimic myasthenia gravis crisis. (Postgrad Med 2000;107:211.)
Standard resuscitation protocols should be used to manage patients with impending respiratory failure or compromise. Succinylcholine can be used safely in patients with myasthenia gravis without risk of precipitating severe hyperkalemia. Patients with myasthenia gravis are relatively resistant to succinylcholine, and when undergoing rapid sequence intubation should receive a large dose of 2 mg/kg to sufficiently stimulate the remaining disease-unaffected acetylcholine receptors. (Ann Emerg Med 2005;45:225.) Myasthenia gravis patients given succinylcholine will tend to have prolonged paralysis, however, compared with those without the disease.
Unlike some causes of respiratory failure, those caused by disease at the neuromuscular junction tend to fluctuate, and no single indication for intubation exists. Cut-off values have been offered to guide treatment, but have not been prospectively validated. (Intensive Care Med 1995;21:663.) Close monitoring in the ICU is recommended for all patients with myasthenia gravis crisis. Elective intubation is recommended for clinical signs of respiratory distress, decreased ability to handle oral secretions, or declines in serial measurements approaching the following threshold values: forced vital capacity of 15 mL/kg or less, tidal volume 5 mL/kg or less, negative inspiratory force of 20–25 cm H2O or less, or positive expiratory force of less than 40 cm H2O. Besides monitoring for respiratory issues, continuous telemetery is recommended because recent studies have shown that 11 percent to 14 percent of myasthenia gravis crisis patients have arrhythmias, ranging from benign to life-threatening. (Postgrad Med 2000;107:211.) Although oxygenation should be monitored, arterial blood gas monitoring is an insensitive measure of respiratory muscle weakness and lag behind after life-threatening compromise has already developed.
If intubation is not required emergently or is not indicated, then identifying a history of recent infection, surgery, or medication change may help to identify the trigger of the event. Standard evaluation for infectious sources may include chest radiographs, urinalysis, laboratory blood tests, and cultures as indicated. A recent history of dysphasia and aspiration episodes may help to quantify the extent of oropharyngeal involvement, and swallowing restrictions are indicated for all crisis patients.
The diagnosis of myasthenia gravis can be established clinically by placing an ice pack on the closed eyelids of a patient with ptosis for one minute. If the patient has myasthenia gravis, ptosis should improve. The diagnosis also can be made with a serologic (antibody) or a Tensilon test. If a patient given Tensilon (edrophonium) has myasthenia gravis, it will increase muscle strength of the affected muscles. These tests have limited value in the ED when a patient is in extremis, such as those with myasthenia gravis crisis.
After initial resuscitation and stabilization, managing the identified triggers is the first course of action. Treatment includes rapid initiation of plasma exchange or intravenous immunoglobulins, immunosuppressive medications, and acetylcholinesterase inhibitors. Treatment should be done in consultation with a neurologist. Plasmapheresis works by directly removing acetylcholine receptor antibodies from the circulation. It produces rapid improvement in 75 percent of patients with severe weakness. (Neurology 1997;48:70S.) Improvement is transient, lasting only three to four weeks, and has not been shown to decrease the duration of crisis or improve mortality. (Neurological and Neurosurgical Intensive Care. New York: Raven Press, 1993.) Another option is initiation of intravenous immunoglobulins (400 mg/kg daily for five days), with symptomatic improvement expected in one to two weeks. Unfortunately, improvement after either of these therapies is transient, lasting only weeks to months. No randomized placebo-controlled trial of IVIG or plasma exchange has been done to date to validate their use. A few studies show that plasmapheresis may have a faster onset than IVIG (Ann Neurol 1997;41:789; Neurology 1999;52:629), and most neurologists still prefer plasmapheresis as a first-line therapy.
Immunosuppressive therapy, in-cluding high-dose prednisone (60–80 mg per day), is initiated to prevent the rebound of circulating antibodies after IVIG or plasma exchange. The onset of benefit is usually within two to three weeks and typically peaks after five and a half months. Unfortunately, it is associated with a transient increase in weakness in 50 percent of patients, with as many as 10 percent requiring re-intubation. Currently it is recommended that immunosuppression be started immediately with rapid plasmapheresis or IVIG therapy so that this paradoxical weakness does not blunt the therapeutic response to the other therapies and maximal benefit is realized after the benefit of the IVIG and plasmapheresis has ended.
Acetylcholinesterase inhibitors can be given as an infusion or orally, but the intravenous form has been associated with fatal arrhythmias (Crit Care Med 1997;25:1228), worsened weakness, and increased secretions (Neurology 1997;48:1253), which may worsen aspiration risks. Current recommendations are to start them after improvement from either plasma exchange or IVIG.
This patient was intubated in the ED, and received IVIG and steroids in the ICU with response. She had a prolonged hospitalization, but was able to be discharged home, but has since had many subsequent visits to the ED for various complaints.
No Improved Survival with Home AEDs
Access to a home automated external defibrillator (AED) does not significantly improve overall survival when compared with conventional resuscitation methods, according to a study in the April 24 New England Journal of Medicine.
Researchers led by Gust H. Bardy, MD, of the Seattle Institute for Cardiac Research, randomly assigned 7000 patients with previous anterior wall myocardial infarction who were not candidates for an implantable cardioverter-defibrillator to receive one of two responses: calling emergency medical services and performing cardiopulmonary resuscitation or using an AED then calling for EMS and performing CPR.
They found that 6.5 percent of patients in the non-AED group died compared with 6.4 percent in the AED-group and that there were no significant differences in mortality in major prespecified subgroups.