Page 1189 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

826 PART 6: Neurologic Disorders

myasthenic crisis, with one study reporting a reintubation rate of 26%. effects of corticosteroids are commonly noted over several weeks, but full
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The presence of atelectasis was the strongest predictor for reintubation benefit may not be evident for months. Azathioprine, mycophenolate,
in this study. Cardiac dysrhythmias are a common cause of death in and cyclosporine have a more delayed onset of action, thereby limiting
patients with myasthenic crisis, and continuous cardiac rhythm moni- their use as a primary agent for initial therapy. Cyclosporine reduces
toring is strongly recommended. acetylcholine receptor antibody production, but toxicity limits its use.
In patients with a compatible clinical presentation, the diagnosis of Cyclophosphamide has also been beneficial in patients who were refrac-
MG centers on three principal studies: a positive anticholinesterase tory to other agents, but toxicity, including increased risk of neoplastic
test (rapid and transient improvement in strength after administration disease, remains a significant concern.
of edrophonium) in patients with obvious ptosis or ophthalmoparesis; Plasma exchange and IVIg are commonly used for intensive short-
presence of acetylcholine receptor antibodies in the serum; and electro- term therapy in patients with severe myasthenic symptoms. 36,44,63-65
physiologic studies that are indicative of a disorder of the neuromuscular Plasma exchange removes acetylcholine receptor antibodies rapidly,
junction, with a decremental response in compound action potentials commonly resulting in an improvement in strength within several days.
to repetitive nerve stimulation. One diagnostic strategy that has been Typically, 2- to 4-L exchanges are performed two to three times per
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recommended begins with an edrophonium test, followed by a repeti- week over a 10- to 14-day period. IVIg also results in rapid improve-
tive nerve stimulation test and measurement of acetylcholine receptor ment in most patients. Limited studies have compared the efficacy of
antibodies. In patients with clear ptosis and concerns for edrophonium PE and IVIg in the treatment of MG, but they appear to offer similar
toxicity (eg, severe asthma, bradyarrhythmia), an ice pack test has been benefits. 36,63-66 With its ability to rapidly reduce antibody levels, PE may
used. This test involves placement of a bag with ice on a closed eyelid for result in more rapid clinical improvement and should be considered
2 minutes and determining the degree of ptosis. 61 as an initial intervention in patients with myasthenic crisis, with IVIg
Eaton-Lambert syndrome is an uncommon disorder of neuro- reserved for possible use after a course of plasma exchange. Worsening
muscular transmission, which may be confused with MG. The of weakness is not uncommon in the early period after treatment with
1,47
Eaton-Lambert syndrome is associated with neoplastic disease in corticosteroids in patients with MG; however, simultaneous treat-
approximately 50% of patients (most commonly small cell carcinoma). ment with PE or IVIg appears to blunt or lessen this adverse effect.
In contrast to patients with MG, the compound muscle action potential Contemporary treatment has significantly reduced the mortality rate for
demonstrates a significant incremental increase following repetitive myasthenic crisis to less than 5%. 48,67
nerve stimulation or maximal isometric muscle activation in patients Thymectomy has been associated with clinical improvement and
with the Eaton-Lambert syndrome. remission in patients with MG, and is generally recommended for
Conditions associated with MG include thymic hyperplasia or patients with thymomas between the ages of puberty and approximately
thymoma, and autoimmune disorders such as rheumatoid arthritis, 60 years. 47,63 However, adequate prospective studies demonstrating
systemic lupus erythematosis, thyroiditis, and Graves disease. Thyroid a clear benefit from thymectomy are unavailable, and postoperative
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function testing should be obtained in all patients with MG. Thymic improvement may not be evident for months to years. Thus, attributing
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abnormalities are present in the majority of patients with MG, with thy- clinical improvement to thymectomy may be difficult. Because postop-
mic hyperplasia being most common and thymoma identified in 10% to erative decline in ventilatory function is common, thymectomy should
12% of patients. Of note, almost all patients with MG and thymoma are not be performed as an emergency procedure in patients with signifi-
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seropositive for acetycholine receptor binding antibodies. The associa- cantly impaired ventilatory function (VC <2 L). To potentially improve
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tion with thymic abnormalities has led to the use of a chest computed respiratory muscle strength, plasma exchange or IVIg should be consid-
tomographic (CT) or magnetic resonance (MR) imaging as a screening ered preoperatively in patients with significant ventilatory impairment.
tool in patients with MG. Alternative therapeutic strategies should be considered in MG patients
The treatment of MG includes anticholinesterase medications to who are refractory to conventional therapy. For example, high-dose
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increase the concentration of acetylcholine available for receptor bind- cyclophosphamide followed by granulocyte colony-stimulating factor
ing, immunomodulating therapy, and thymectomy. 47,63 Serial neuromus- therapy has been reported to be effective in patients with MG refrac-
cular examinations have been the principal method of following patients tory to conventional immunosuppressive therapy, plasma exchange, and
and determining their response to therapeutic interventions. The first thymectomy. 68,69 In addition, lymphocyte depletion therapy with rituximab
line of therapy is use of an anticholinesterase agent, most commonly has been demonstrated to be an efficacious and well-tolerated option for
pyridostigmine, which reduces the degradation of acetycholine, allowing conventional drug-resistant MG, and appears to offer the greatest durable
for greater acetylcholine concentration at the neuromuscular junc- benefit in the subset of patients with autoantibodies to MusK. 70
tion. Respiratory muscle function improves in approximately 50% of
patients treated with anticholinesterase medications. Muscarinic side Dermatomyositis and Polymyositis: Dermatomyositis and polymyosi-
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effects include abdominal cramping with frequent defecation, increased tis are acquired idiopathic inflammatory disorders, which usually
urinary frequency, bronchospasm, bradycardia, fasciculations, increased present with progressive symmetrical muscle weakness over several
oral secretions, and excessive lacrimation. Less commonly, these agents months. 71,72 Less commonly, there is an acute presentation with rapidly
produce a cholinergic crisis, with increased bulbar and lower respira- evolving muscle weakness. Of the major muscle groups, the shoulder
tory muscle weakness during the early phase of treatment. The clinical and pelvic girdle muscles are most often affected. Neck flexion muscles
manifestations of a cholinergic crisis may overlap with those of a myas- are weakened in up to 50% of patients, but facial muscles are usually
thenic crisis, making a clear distinction difficult; withholding anticho- spared. Pharyngeal muscle involvement may present with dysphonia
linesterase medications for 4 to 10 days may be necessary to make this or dysphagia. Myalgias and muscle tenderness occur in up to 50% of
distinction. However, anticholinergic drugs should be used in caution in patients. An immune-mediated mechanism is strongly supported by
patients with MusK autoantibodies as these patients often demonstrate the association of PM/DM with other autoimmune diseases, and by the
acetylcholine hypersensitivity. 63 frequent presence of autoantibodies in serum.
Although most patients respond to anticholinesterase therapy, their Diagnostic criteria for PM/DM include the presence of symmetrical
response is usually incomplete and symptomatic relapse during therapy proximal muscle weakness, elevated skeletal muscle enzymes, and com-
is common. Unfortunately, increasing the dose of drug often leads to patible findings on electromyography and skeletal muscle biopsy. 71,72
significant side effects. Thus, the majority of patients require additional Characteristic dermatologic findings are present in dermatomyositis,
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therapy with immunosuppressive agents. 47,63 Corticosteroid use results including heliotropic changes of the eyelids and Gottron sign, a char-
in a remission or marked improvement in approximately 75% of patients acteristic symmetric erythematous rash over the extensor surfaces of
with MG, and these are the most commonly used agents. The beneficial metacarpophalangeal, interphalangeal, elbow, and knee joints. Myalgias

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