Most patients with myasthenic crisis take several weeks to recover, and a few of our patients have remained ventilator-dependent for months. In the extensive experience of 53 patients from Columbia-Presbyterian, half of the patients could be safely extubated within 2 weeks and three-quarters by a month (Thomas et al). There were 7 deaths among 53 patients, reflecting the gravity of this syndrome even in the modern era of intensive care. Atelectasis, severe anemia, congestive heart failure, and clostridial diarrhea (associated with antibiotic use) portend a prolonged period of generalized weakness and intubation. From time to time, one encounters a patient in whom respiration and ambulation do not improve for many months after a myasthenic crisis. In our experience these have been middle-aged or older patients, usually women, in whom an element of hyperthyroidism or hypothyroidism may have been operative. They become wasted as the proximal limb and axial muscles, including the diaphragm, fail to recover their power, even though the ocular and oropharyngeal muscles improve. The role of corticosteroids in producing a concomitant proximal myopathy is a consideration that can be solved by careful electrophysiologic examination.
If the response to anticholinesterase drugs is poor and progressively larger doses are not relieving symptoms, there is consideration of a cholinergic crisis. In our own experience with more than 80 patients of severe myasthenia in an intensive care unit, we have been persuaded of the occurrence of a cholinergic crisis only rarely. This consists of a relatively rapid increase in muscular weakness, usually coupled with the adverse muscarinic effects of the anticholinesterase drug (nausea, vomiting, pallor, sweating, salivation, bronchorrhea, colic, diarrhea, miosis, bradycardia). An impending cholinergic effect is betrayed by constriction of pupils. If the blood pressure falls with bradycardia, 0.6 mg atropine sulfate may be given slowly by the intravenous route. Neostigmine or repetitive stimulation may be used to determine whether or not weakness is to the result of an excess of anticholinesterase medications. However, this test has been misleading and undoubtedly has contributed to an overestimation of the frequency and importance of the cholinergic crisis. Infection, or the natural course of the disease, has been far more common causes of acutely worsening weakness and respiratory failure.
The only recourse in cases of long-standing and severe, intractable myasthenia is to continue an average dose of corticosteroids, immunosuppressive, and anticholinesterase medications with intermittent trials of immune globulin or plasma exchanges. This is also a desperate situation in which high-dose cyclophosphamide followed by granulocyte-stimulating factor, as mentioned earlier, may result in slow improvement. Other agents such as rituximab may be tried. Whether thymectomy, undoubtedly risky in these sick patients, effects severe and long-established myasthenia is not known but its effects in any case, would be delayed.