Neurocritical Care

24. Weaning of the Ventilator in Myasthenia Gravis

A 60-year-old man with a recent diagnosis of myasthenia gravis developed shortness of breath and trouble keeping his head up. In the following days he developed difficulty with swallowing. He was admitted to an outside hospital, where he received three infusions of intravenous immunoglobulin (IVIG), but was found “unresponsive” on the fourth day with an arterial PCO2 greater than 110 mmHg and a pH of 6.8 requiring emergency intubation. He awakened quickly after arterial PCO2 correction, but was found to be profoundly weak. Chest X-ray showed only minor atelectasis. He was transferred to our neurosciences intensive care unit. He was started on oral prednisone and plasma exchange. After 3 exchanges, his muscle strength was significantly better and coughing appeared strong.

He was extubated and maintained good oxygenation for several hours; however, during the day, he became increasingly tachypneic and was placed on BiPAP.

His neurologic examination shows good neck flexion, hoarseness, and weak coughing up of secretions. Muscle strength is good in all extremities with no hint of fatigable weakness. However he is barely tolerating BiPAP and is having more trouble with pooling of secretions. Arterial PCO2 climbs to 55 mmHg, and he is reintubated. Chest X-ray shows marked atelectasis of the left lung (Figure 24.1).

What do you do now?

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FIGURE 24.1 Hypersecretion and neuromuscular respiratory failure in myasthenia gravis. Serial X-chest showing marked left atelectasis from a mucus plug (A) and gradual improvement after intubation and bronchoscopy (B, C).

How do you safely get a patient with a recent flare-up of myasthenia gravis off the ventilator and keep him off the ventilator? For one thing, management of myasthenic crisis with neuromuscular respiratory failure remains poorly defined and largely empirical. Quite a few patients will have to be intubated and reintubated. Many do improve rapidly after specific therapy—IVIG, or plasma exchange. A recent analysis concluded that the treatment effects of these two options in myasthenia gravis-and possibly myasthenia crises- are comparable. Delay of treatment however increases mortality and complications.

After neurologic improvement, weaning from the ventilator becomes a priority. Liberating myasthenic patients from the ventilator, however, remains frustrating for most attending physicians. Moreover, pulmonary infections and atelectases can make weaning even more challenging.

Most neurologists will try to find an adequate dose of pyridostigmine that improves muscle strength and oropharyngeal function and could assist in weaning the patient off the ventilator. However, at the same time a dose of pyridostigmine must be found that does not cause abundant secretions. Thick secretions will predispose the patient to sudden mucus plugs, which, as it was in our case, may occlude a large bronchial branch.

There are some prerequisites to consider for physicians attempting to wean the patient from the ventilator. The first priority remains satisfactory treatment of the myasthenic symptoms. This is best accomplished with plasma exchange in the acute phase. In our experience, once the patient is severely affected and intubated, IVIG less frequently will lead to substantial improvement. Multiple bronchoscopies may be necessary to clear the bronchial tree from secretions, and often an infection becomes apparent that requires specific antibiotic treatment. Only after the secretions and infection are under control can the patient be considered for weaning. In some instances, early tracheostomy is necessary to better clear secretions from the airways.

Treatment with immunosuppressive drugs should be started, and usually this includes prednisone 60 to 90 mg and perhaps a pulse-dose of methylprednisolone (intravenous infusion of 1 gram). Long-term treatment with mycophenolate mofetil, for example, will only take effect several weeks after initiation and cannot be relied on in the acute phase of management.

The prediction of success of extubation is difficult to determine clinically, and we have not found a good way to do it. Some of the extubation parameters described in neuromuscular respiratory failure and their predictive values are shown in Table 24.1. Oropharyngeal function is hard to assess in an intubated patient, and neck flexion or shoulder shrug do not predict failure. Often the patient is extubated, seemingly doing well and holding his own, only to deteriorate with increased work of breathing, shallow breathing, and gradual rise in arterial PCO2. In our patient example, this deterioration was also further complicated by acute mucus plugging that resulted in reintubation.

Several tests have been developed that might be useful in assessing the probability of successful extubation. One recent study proposed the use of a so-called white card test. This white card is placed 1 to 2 cm from the end of the endotracheal tube and any moisture present on the card following two to three coughs is considered a positive test. The patients are positioned with the head of the bed at 30 to 45 degrees and coached to cough maximally. It is unclear whether this test is a better predictor than a simple clinical assessment of cough strength. Another possibility is to place the patient on a spontaneous breathing trial and observe respiratory frequency and tidal volume for about an hour. We recommend that, extubation can be followed by bilevel positive airway pressure (BiPAP) noninvasive ventilation, which augments airflow and maintains positive airway pressure in the inhalation and exhalation phases.

TABLE 24.1 Predictors for Successful Extubation Parameters in Myasthenia Gravis

Test

Predictive Value

Secretion volume

Good

T-piece trials (with assessment of rapid shallow breathing)

Good

Normal chest X-ray

Good

Neurologic examination (oropharyngeal function, head-flexion strength)

Uncertain

White card test

Uncertain

Pulmonary function tests

Poor

The strongest risk factor for extubation failure in myasthenic patients is the presence of atelectasis on chest X-ray. Patients may also fail extubation if there is a significant secretion volume (an arbitrary judgment), evidence of a recent yet not sufficiently treated pneumonia, and pulmonary edema prior to extubation. It should also be pointed out that the respiratory pump needs sufficient strength and thus pyridostigmine is key. It is very difficult—and probably too stressful for the patient—to try weaning the ventilator without pyridostigmine. Simply said, breathing does not work if the bellows don’t work.

Finally patients may also develop post-extubation stridor. One recently noted complication is that vocal cord abduction paralysis may occur in the anti-MuSK variant of myasthenia gravis.

So after these events how should we proceed with our patient? How can we get the infected secretions under control and wean from the ventilator safely? It was decided to place a tracheostomy, and after a week, cultures came back with a multiresistant pseudomonas that was treated with aerosolized colistin. The patient gradually improved, although multiple bronchoscopies were needed to clear the secretions. A gradual decrease in pyridostigmine possibly also contributed to the decrease in secretions, and the patient was transitioned—in incremental steps—to pressure support and eventually to spontaneous breathing trials.

Treatment of myasthenia gravis with acute neuromuscular respiratory failure takes time. In our patient it took about 6 weeks before he could be dismissed from the hospital. Patients with myasthenia gravis and difficulties getting off of the ventilator often have had prior episodes of crisis, and in these cases a prolonged period of hospitalization can be anticipated.

KEY POINTS TO REMEMBER REGARDING WEANING OF THE VENTILATOR IN MYASTHENIA GRAVIS

· Reintubation is common in myasthenia gravis, especially in patients with bronchial hypersecretion and atelectasis.

· Long-term management with placement of a tracheostomy is needed after reintubation.

· Finding an optimal dose of pyridostigmine after treatment of myasthenic crisis is difficult. There is a fine line between minimizing secretions and optimizing the strength of oropharyngeal and respiratory muscles.

· PLEX is the preferred treatment in myasthenic patients with severe neuromuscular respiratory muscle weakness.

· PLEX may not be sufficient to wean a patient off the ventilator, and pyridostigmine is needed to improve respiratory muscle function.

Further Reading

Chaudhuri A, Behan PO. Myasthenic crisis. QJM 2009; 102:97–107.

Frutos-Vivar F, Ferguson ND, Esteban A et al. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest 2006; 130:1664–1671.

Jani-Acsadi A, Lisak RP. Myasthenia gravis. Curr Treat Options Neurol 2010; 12 231–243.

Khamiees M, Raju P, DeGirolamo A, Amoateng-Adjepong Y, Manthous CA. Predictors of extubation outcome in patients who have passed a trial of spontaneous breathing. Chest 2001; 120:1262–1270.

Lacomis D. Myasthenic crisis. Neurocrit Care 2005; 3:189–194.

Mandawat, A., Kaminski, H. J., Cutter, G et al. Comparative analysis of therapeutic options used for myasthenia gravis. Ann. Neurol 2010;68: 797–805

Mandawat A, Mandawat A, Kaminski HJ et al. Outcome of plasmapheresis in myasthenia gravis: delayed therapy is not favorable. Muscle Nerve 2011;43:578–584

Seneviratne J, Mandrekar J, Wijdicks EFM, Rabinstein AA. Predictors of extubation failure in myasthenic crisis. Arch Neurol 2008; 65:929–933.

Sylva M, van der Kooi AJ, Grolman W. Dyspnoea due to vocal fold abduction paresis in anti-MuSK myasthenia gravis. J Neurol Neurosurg Psychiatry 2008; 79:1083–1084.