Page 1188 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 87: Neuromuscular Diseases Leading to Respiratory Failure 825

because of an exaggerated hypotensive response to sedative agents and Myasthenia Gravis: Myasthenia gravis (MG) is an acquired autoim-
a markedly increased risk of arrhythmias, most often bradyarrhythmia. mune disorder of neuromuscular junction transmission characterized
Guillain-Barré syndrome is a monophasic illness with a fairly predict- by muscle weakness, progressive muscle fatigue with repetitive use, and
able natural history; at least 90% of patients reach the nadir of their neu- improvement in strength after rest. The incidence of MG is highest
47
romuscular impairment by 4 weeks. Most patients with GBS survive in younger women or older men. Myasthenia gravis has two clinical
48
5,12
with significant recovery of neuromuscular function. Approximately presentations: ocular and generalized. In patients who present with the
two-thirds of patients experience mild residual long-term deficits, and more limited ocular form, approximately 50% will develop generalized
10% to 20% of patients recover completely. Severe disability may persist weakness during the first 2 years of their illness. Generalized weakness
in as many as 20% of patients, and 3% to 8% of patients will die as a with fatigability involving the neck, trunk, and extremity muscles is
result of pneumonia, acute respiratory distress syndrome, sepsis, pulmo- noted in approximately 85% of patients and may be the dominant com-
nary emboli, or cardiac arrest. 12,24,31,32 One study derived from a cohort plaint. Fluctuation in the degree of muscle weakness is a characteristic
47
of 397 patients identified three poor prognostic indicators for the ability finding in patients with MG, with patients commonly noting increased
to walk at 4 weeks to 6 months after the onset of GBS: increased age; weakness later in the day and following exertion. Isolated weakness of
reduced muscle strength on admission and at 1 week quantified by the the extremities is uncommon. Ocular muscle involvement, including
MRC sum score; and the presence of preceding diarrhea. 33 ptosis and diplopia, is often noted on presentation. Facial muscle weak-
Sudden death has been observed in patients with severe autonomic ness may lead to difficulty in smiling, an appearance referred to as the
dysfunction. Deaths appear to be more common in the elderly, particu- “myasthenic sneer.” Bulbar muscle impairment results in dysarthria and
larly in patients with preexisting pulmonary disease. In addition, the difficulty in both chewing and swallowing, with an increase in the risk
31
mortality and morbidity of GBS is strongly associated with the need for for aspiration.
and duration of mechanical ventilation. The mortality rate of patients The immunopathogenesis of MG has been relatively well defined, with
with GBS who require mechanical ventilation may be as high as 20%. identification of autoantibodies that bind to the acetylcholine receptor
34
Mechanical ventilation for more than 2 weeks has been found to be the (Ach R), resulting in a significant reduction in the number of available
strongest predictor of major morbidity by multivariate analysis, with receptors at the neuromuscular junction, thereby impairing neuromus-
lower respiratory tract infection being the most common complication. 35 cular transmission. Acetylcholine receptor–binding antibodies are
47
Treatment of GBS involves either plasma exchange (PE) or intra- identified in approximately 88% to 93% of patients with generalized MG,
venous immune globulin (IVIg). 36,37 However, approximately 20% of and in approximately 71% of patients with symptoms limited to ocular
patients die or develop persistent severe disability despite therapy with muscle involvement. Autoantibodies to muscle specific receptor tyro-
49
PE or IVIg. Plasma exchange was demonstrated to improve strength sine kinase (MusK) have also been identified in patients with MG. The
37
and reduce the incidence of respiratory failure in three multicenter trials subset of patients who are Ach R antibody negative and MusK antibody
conducted in the 1980s. 38-40 The ability of PE to rapidly reduce antibody positive are more often female with an oculobulbar pattern, respiratory
levels is the most likely mechanism underlying the improvement in mus- and proximal muscle weakness, lack of thymic abnormalities, limited
cle strength. Only one or two exchanges may be needed in patients with response to acetylcholinesterase inhibitors, and responsive to treatment
mild impairment, whereas four to five exchanges appear to be optimal with PE and IVIg. 50,51
in those with more severe impairment. Outcome appears to be better Although isolated involvement of the respiratory muscles may occur,
41
if PE is initiated during the first 7 days of symptoms, although delayed respiratory muscle impairment typically presents along with generalized
treatment with PE may still result in clinical improvement. Albumin is muscle weakness. 52,53 Upper airway obstruction with abnormal vocal
as effective as fresh frozen plasma as a replacement fluid during plasma cord adduction during inspiration has also been described. Lower
54
exchange, and is associated with fewer adverse reactions. 42 respiratory muscle impairment is evidenced by a significant reduction
IVIg has also been shown to be an effective therapy for GBS. 36,37,43,44 in VC, MIP, and MEP. Approximately 15% to 27% of patients experi-
The mechanism by which IVIg benefits patients with GBS is not fully ence “myasthenic crisis,” a rapid and severe decline in respiratory muscle
defined, but neutralization of neuromuscular blocking antibodies by function that is associated with a mortality of 4% to 13%. 48,55-57 Multiple
a dose-dependent process appears likely. A randomized, multicenter, triggers for myasthenic crises have been identified, with infection being
45
international trial compared plasma exchange, IVIg, or plasma exchange the most common, followed by medication changes and surgery. Other
20
followed by IVIg in 379 GBS patients who had marked weakness and triggers include electrolyte abnormalities, trauma, surgery, pregnancy,
whose symptoms had been present for 14 days or less. There were withdrawal of anticholinesterase drugs, and the use of drugs that impair
32
no differences among the three treatment groups with regard to either neuromuscular transmission. 58,59 However, a trigger for the myasthenic
the duration of mechanical ventilation or functional outcome 4 weeks crisis cannot be found in nearly a third of patients. 56
after therapy. It was therefore concluded that IVIg and plasma exchange The use of NIV in patients with myasthenic crisis was examined in a
are equally effective therapies, and that their combined use offered retrospective cohort study of 60 episodes of myasthenic crisis with respi-
no additional benefit. Of note, plasma exchange should not be used ratory failure. In this study, NIV was initially applied in 40% of patients
20
immediately after IVIg, since this therapeutic sequence would remove and the remaining 60% were intubated without prior use of NIV.
antibodies administered with IVIg. Because of its ease of administration, Intubation was eventually performed in 42% of those initially managed
availability, and acceptable side-effect profile, IVIg is often preferred, with NIV. The only predictor for NIV failure was a Pa CO 2 >45 mm Hg
particularly in hemodynamically unstable patients in whom PE may be at the time of NIV initiation. Even though the baseline patient charac-
associated with worsening hypotension. The optimal duration of IVIg teristics were similar in those initially managed with NIV or intubation,
therapy has not been determined; however, patients with more severe the duration of assisted ventilation was significantly shorter in patients
weakness may benefit from more prolonged courses of IVIg and 5 days who were initially treated with NIV, offering an argument for the early
of treatment is commonly offered. In addition, IVIg may be superior use of NIV in patients with myasthenic crisis and respiratory failure.
36
to PE in patients with Campylobacter jejuni infections and antibodies Of note, bulbar weakness was present in all patients with myasthenic
to peripheral nerve gangliosides. Although information is unavailable crisis reported in this study. In a retrospective study of 73 episodes of
46
regarding the optimal management of patients who fail to improve or myasthenic crises progressing to intubation, 50% of patients were extu-
relapse, retreatment with IVIg or PE is commonly recommended. Of bated within 2 weeks, and the median ICU and hospital stays were 14
note, screening for IgA deficiency is recommended prior to treatment and 35 days, respectively. Three independent predictors of prolonged
56
with IVIg to reduce the risk of anaphylaxis during infusion. Although intubation were identified in this study: preintubation serum bicarbon-
frequently used in the past, corticosteroids have not been shown to be ate ≥30 mEq/L; peak VC <25 mL/kg on day 1 to 6 postintubation;
beneficial in patients with GBS. 37 and age >50 years. Extubation failure is common in patients with

section06.indd 825 1/23/2015 12:56:19 PM