AANA Journal Course

Update for nurse anesthetists

*6 CE Credits

Etiology, mechanisms, and anesthesia implications

of autoimmune myasthenia gravis
MAJ Thomas E. Ceremuga, CRNA, MSN, AN, USA
Xiang-Lan Yao, MD, PhD
Joseph T. McCabe, PhD
Bethesda, Maryland

Myasthenia gravis (MG) is the prototypical neurological

autoimmune disease. It is characterized by muscle weakness
that progressively worsens on repetition but improves with
rest. Muscle weakness and fatigability arise from defective or
decreased acetylcholine receptors at the neuromuscular junctions, where nerve signals from spinal motor neurons that
innervate muscles cannot effectively induce muscle contraction. Several mechanisms of pathogenesis lead to the MG syndrome. The most prevalent cause of MG is an autoimmune disorder in which the patient produces antibodies that attack the

nicotinic acetylcholine receptor at the neuromuscular junction.

Anesthesia management of the patient with MG is challenging
and requires specific management; however, safe and successful outcomes are achievable. This course emphasizes the
autoimmune neuromuscular defect in MG, current treatments
for this syndrome, contraindications of certain anesthetic
drugs in this condition, and anesthetic management of a
patient with MG in the operating room environment.
Key words: Acetylcholine receptor, autoimmune disease, myasthenia gravis, receptor, neuromuscular junction.

Objectives

Introduction

At the conclusion of this course, the reader should be

able to:
1. Discuss the pathologic processes related to the
neuromuscular junction in autoimmune myasthenia gravis.
2. Identify the cellular autoimmune events occurring in myasthenia gravis.
3. Describe the various modalities used in the treatment of myasthenia gravis.
4. Identify the pharmacologic agents that reduce
neuromuscular transmission in patients with
myasthenia gravis and should be avoided in the
perioperative period.
5. Discuss the prudent delivery of anesthesia and the
anesthetic plan for patients with myasthenia
gravis.

Myasthenia gravis (MG) is the prototypical neurological autoimmune disease. Willis first described the malady in 1672, but it was not until 1895 that Jolly used
the name, myasthenia gravis.1 Jolly described a condition of 2 boys who exhibited muscle weakness that progressively worsened on repetition but improved with
rest.1 Muscle weakness and fatigability arise from
defective or decreased acetylcholine receptors (AChRs)
at the neuromuscular junctions (NMJs), where nerve
signals from spinal motor neurons that innervate muscles cannot effectively induce muscle contraction.
Various mechanisms of pathogenesis lead to the MG
syndrome. Congenital myasthenias are caused by a
variety of genetic defects (eg, ion channels or subunits
of AChR mutations) of the presynaptic or postsynaptic
machinery of the NMJ.2 Lambert-Eaton myasthenic syn-

* The American Association of Nurse Anesthetists is accredited as a provider of continuing education in nursing by the American Nurses Credentialing
Center Commission on Accreditation. The AANA Journal course will consist of 6 successive articles, each with objectives for the reader and sources for
additional reading. At the conclusion of the 6-part series, a final examination will be printed in the AANA Journal. Successful completion will yield the
participant 6 CE credits (6 contact hours), code number: 24623, expiration date: July 31, 2003.

AANA Journal/August 2002/Vol. 70, No. 4

301

drome frequently is associated with neoplasms and

involves a dysregulation of presynaptic acetylcholine
(ACh) release. It seems that the presynaptic defect
involves an alteration in calcium channels and, consequently, decreased release of acetylcholine into the
synapse.3,4 The most common cause of MG is an
autoimmune disorder in which the patient produces
antibodies that attack the nicotinic acetylcholine receptor at the NMJ.5 This article emphasizes the autoimmune neuromuscular defect in MG, current therapy for
this syndrome, contraindications of certain anesthetic
drugs in this condition, and anesthetic management of
a patient with MG in the operating room environment.

Figure 1. Edrophonium test

History and review of the literature

Autoimmune neuromuscular MG. The hallmark
features of autoimmune MG are fatigue, increasing
weakness with repetitive motion, and a higher incidence in women.6 Characteristics and symptoms of MG
reflect the dysfunctional AChR at the NMJ, including
generalized weakness in 85% of patients and limited
weakness of ocular muscles in 15% of patients with
ocular MG.7 While ocular MG is less prevalent, ocular
muscle problems, such as ptosis or diplopia, usually are
the initial complaint, with subsequent progression to
the generalized disease.8 Patients with generalized MG
complain of dysphagia, dysphonia, proximal limb muscle weakness, and even exacerbation to dyspnea or ventilatory failure (myasthenic crisis).9 In 85% to 95% of
patients with MG, a thymic abnormality, such as thymoma or thymic hyperplasia, may be responsible for
secretion of AChR antibodies.10
Diagnostic testing for MG includes pharmacologic,
electrophysiologic, and laboratory testing. Edrophonium, an anticholinesterase (anti-AChE), is administered to inhibit the enzyme that degrades ACh; therefore, more ACh remains at the synapse. The patient
with MG (Figure 1) usually demonstrates a temporary
reversal of muscle weakness with edrophonium.11
Nerve conduction tests, such as repetitive nerve stimulation, also are performed to verify the MG diagnosis.
Motor response is monitored after the nerve is stimulated repetitively at the rate of 2 Hz, and the patient
with MG usually exhibits a gradual decrease in amplitude.12 In addition, serum AChR antibodies are assayed
to confirm the diagnosis; results for 90% to 95% of
patients with MG are positive.10 The positive results
from these testing modalities point to a defect in the
NMJ in the patient with MG.
The neuromuscular junction. Proper functioning of
the NMJ is required for impulse propagation and muscle contraction. The NMJ is a complex structure, composed of the motor nerve terminal, postsynaptic muscle surface, and specialized basal lamina (Figure 2).

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(A) Patient with myasthenia gravis with ptosis

(B) Patient after receiving 10 mg of edrophonium
12
(From Pourmand. Reproduced by permission of Mosby, Inc.)

Nerve terminal endings are located presynaptically in

the primary synaptic clefts at the synapse. The muscle
surface area, postsynaptically, is enlarged by invaginations of the plasma membrane into secondary synaptic
folds. The AChRs are located primarily at the distal
extents of the folds, in closer apposition to the nerve
terminals.6 There is continual AChR turnover, in which
old receptors are internalized and degraded, and new
receptors are synthesized and inserted into the synaptic
folds.6 Skeletal muscle sodium channels are located in
the depths of the folds, and AChE, the enzyme that
hydrolyzes ACh, is located at the basal lamina of the
secondary synaptic fold.6
The generation of a muscle action potential and,
ultimately, muscle contraction begins with the depolarization of the presynaptic nerve terminal. This leads to
calcium influx via channels and calcium-dependent
fusion of synaptic vesicles with presynaptic nerve terminal membrane in the nerve boutons. Fusion allows
the release of ACh into the synapse, where the neurotransmitter then can diffuse across the synaptic cleft
and bind to AChRs. If a large enough quantity of ACh
is released, a muscle endplate potential is reached,
resulting in postsynaptic depolarization and muscle
contraction. ACh is removed by AChE hydrolysis and
by diffusion.6
Adult human AChR (Figure 3) is part of a superfamily of neurotransmitter-gated ion channels, and its
pentameric (5-subunit) structure includes 2 and 1
each of the , , and subunits. Fetal AChR is similar,
except a subunit is substituted for the subunit.13,14
The fetal AChR is retained in adult thymic myoid
cells15 and adult ocular muscle fibers.16 The adult
AChR subunits (see Figure 3) are believed to be
arranged around a central ion channel in the following

Figure 2. Normal human neuromuscular junction

Axon

Nerve
terminal

Mitochondria
Vesicle

Release site

Acetylcholine
Acetylcholine
receptor
Muscle
(end-plate)
Acetylcholinesterase
Basal lamina

12
(From Pourmand. Reproduced by permission of Mosby, Inc.)

Figure 3. Acetylcholine receptor (AChR) subunits: fetal (left) and adult (right)

Subunits: 1, 1, , ,

Muscle AChRs

(1) 2 1

(1)2 1

Fetal form

Adult form

ACh binding site

at subunit interface
18
(From Lindstrom. Reproduced by permission of John Wiley & Sons, Inc.)

order: 111.17 The ACh binding sites are formed

at the union of the 1 and and the 1 and subunits.18 Both binding sites must be occupied by an agonist (ACh) for the ion channel to open.19 The binding
of ACh to both sites results in a conformational change
in the AChR and channel opening.14 Conversely, if an
antagonist (eg, vecuronium) binds one site, channel
opening is prevented.18
Autoimmune pathology. A region located on the
extracellular tip of the 1 subunits has been described
as the main immunogenic region. Since the main
immunogenic regions are located at the outer (extracellular) portion of the AChR, they are easily recognized by antibodies.20 A single antibody is unable to
cross-link 2 1 subunits but easily cross-links (Figure

4) 2 adjacent AChRs.21 These properties and characteristics of the main immunogenic region facilitate the
pathogenic mechanisms involved in the autoimmune
response to AChRs.18
The evidence that links AChR antibodies as the
causative factor in MG includes the following: (1) Of
patients with MG symptoms, 85% have these antibodies.10 (2) Immunoglobulin G (IgG) has been found at
the neuromuscular endplate.22 (3) Plasmapheresis to
reduce circulating antibodies provides temporary
symptomatic relief.23 (4) Healthy animals injected with
antibodies against AChR produce MG signs.24 There
also is the possibility that the antibodies bind to or near
the ligand-binding site.7 Antibodies also can cross-link
AChRs resulting in internalization, increased degradaAANA Journal/August 2002/Vol. 70, No. 4

303

Figure 4. Cross-linked acetylcholine receptors (AChRs) by antibody to main immunogenic region (MIR)

AChRs cross-linked
by antibody to the MIR

Extracellular
Transmembrane
Cytoplasmic

18
(From Lindstrom. Reproduced by permission of John Wiley & Sons, Inc.)

tion rate, and a decrease in AChR density at the endplate. This increase in AChR degradation correlates
well with clinical manifestations of MG.25
Moreover, complement-mediated destruction of the
NMJ occurs as a result of AChR antibodies. Antibodies
bind to the C9 component of complement (part of the
immune system involved in cell destruction), triggering an inflammatory cell response, endplate membrane
degradation, and destruction of junctional folds that
harbor AChR-abundant membranes (Figure 5). This
inevitably would reduce the membrane surface available for AChR insertion.26 Therefore, the autoimmune
response in MG affects many components of the
machinery at the postsynaptic membrane, resulting in
altered depolarization of muscle tissue.
Morphological studies of the NMJ in MG demonstrate the following postsynaptic anomalies (Figure 6):
decreased quantity of AChR,27 widened and decreased
machinery of the postsynaptic fold, and increased gap
between presynaptic and postsynaptic membranes.28
Therefore, the primary pathologic mechanism of MG is
a reduction in AChRs and, thus, a reduction in the endplate potential that is not strong enough to reach
threshold potential, depolarization of muscle membrane, and resultant muscle contraction.12 If this transmission failure occurs at many junctions, the strength
of the muscle contraction is reduced and the patient
becomes weak. Normally, only 25% to 30% of AChRs
are necessary for neuromuscular transmission. The
remaining 70% to 75% of receptors represent a safety
margin.29 In MG, there is a decrease in the number of
functional AChR and a decrease in the safety margin.
Cellular autoimmunity mechanisms. The precipitating events that cause MG are not completely understood, but evidence implicates the thymus, as altered
thymic function has a 90% prevalence in this disease.30
For example, thymoma or hyperplasia of the thymus
occurs in high frequency in patients with MG, T and B
cells have an active role in antibody formation, myoid
cells of the thymus gland have the same type of surface
as AChR, and thymectomies usually are beneficial for
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patients with MG.12 There seem to be different trigger

mechanisms of autoimmunity for the various forms of
MG. The patient with rheumatoid arthritis may trigger
an MG syndrome by taking penicillamine, which is
believed to react covalently with AChRs, producing
new antigenic sites.31 This MG condition is reversible
with the termination of penicillamine. A paraneoplastic
immune response may account for the 12% of patients
with MG who have a thymoma, for they have different
HLA marker frequencies than do other patients with
MG. This indicates a probable difference in immune
system genetic background.32 They have not only high
levels of AChR antibodies, but also antibodies to several muscle proteins in the interior of the cells.33 In
most MG cases, the immunogen is likely the native
muscle AChR or a closely related protein. The fetal type
( subunit) has been implicated as the immunogen, as
selective reaction with fetal AChRs has been reported
with antibodies from patients with MG.34
Molecular mimicry by microbes also has been suggested to be responsible for the autoimmune response
in MG, in which bacterial or viral proteins initiate the
immune response, then reaction with the AChR leads
to epitope (antigenic determinant) spreading. In addition, both bacteria and viruses can express superantigens that nonspecifically activate many T and B cells.18
Although the B cells synthesize the autoantibodies to
AChR, there is evidence for a T-cell role in autoimmunity,35 as T cells from patients with MG seem to
respond to AChR stimulation and aid in the production
of AChR antibodies.36 Helper T cells found in patients
with MG can increase the synthesis of anti-AChR antibodies. In MG, T-helper lymphocytes are required to
cooperate with B lymphocytes in promoting autoantibody synthesis.37 The autoantibodies in MG are polyclonal and heterogeneous and recognized different epitopes on the AChR.38,39

State of the art

Treatment of MG. Treatment modalities usually
reflect the rate of progression, severity, and weakness

Figure 5. (A) Normal neuromuscular junction: arrow is synaptic cleft, asterisk is the secondary cleft. (B) Lytic C9
complement component of myasthenic neuromuscular junction showing synaptic degeneration; asterisk is the
junctional folds without nerve terminal and arrrow is presynaptic staining.

12
(From Pourmand. Reproduced by permission of Mosby, Inc.)

Figure 6. (A) Normal neuromuscular junction; (B) neuromuscular junction in myasthenia gravis (MG)

AChR = acetylcholine receptor

12
(From Pourmand. Reproduced by permission of Mosby, Inc.)

distribution of the patient. Age, sex, and the presence

of concomitant diseases also influence long-term therapy decisions. In general, the treatment for MG consists
of 5 modalities: anticholinesterase drugs, immunosuppressants, thymectomy, plasmapheresis, and intravenous immunoglobulins (IgG).40
Anticholinesterases usually are the initial therapy
and provide symptomatic improvement in muscular
strength, as they inhibit the enzyme that degrades ACh.
This allows ACh to remain longer at the NMJ, increasing the probability for ACh binding to AChRs.
Immunosuppressant drugs (eg, corticosteroids, azathioprine, and cyclosporine) are administered to
decrease the immune response and modulate mechanisms in cellular immunity.40 Since thymic abnormalities (hyperplastic changes and neoplasias) are prevalent
and evidence suggests they are intricately involved in
many forms of MG, surgical thymectomies are also performed.41 As mentioned previously, it is hypothesized

that autoreactive T cells are activated in the thymus.42

Studies indicate that thymectomies decrease T-cell reactivity against disease-specific antigens and provide
symptomatic relief .43 In addition, if the source of the
immunogen is thymic myoid cells, their elimination
may decrease the immune response44 as a possible
reservoir of AChR antibody-producing B cells may be
removed with this operation.45 Plasmapheresis usually
is used as a short-term treatment in patients with
extreme weakness. This treatment is believed to
remove circulating AChR antibodies and immune complexes, often resulting in rapid improvement, which
lasts 6 to 8 weeks.40
In addition to plasmapheresis, intravenous immunoglobulins (IgG) have been used in the extremely
weakened patient with acute MG. The mechanism by
which IgG improves MG symptoms is unclear but is
speculated to involve the interaction between autoantibodies and anti-idiotypic (nonspecific) antibodies in
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305

IgG preparations.46 Future treatment modalities are

being considered with a more cell-directed approach,
such as monoclonal antibodies directed against helper
T cells and administration of immunotoxins that would
destroy B cells specific for AChRs.7,47
Anesthesia pharmacology contraindications. The
hallmark symptom of muscle weakness, especially after
repetitive stimuli, can lead to dangerous and life-threatening situations for the patient with MG. One such
environment or condition is surgery (often an elective
thymectomy) and, more important, the administration
of anesthesia during the surgical procedure. MG is a
condition of particular interest to anesthesia as it
involves the NMJ, the site of action of many commonly
used anesthetic drugs. There are many pharmacologic
agents used in anesthesia that can lead to devastating
consequences and even precipitate a myasthenic crisis
in the patient with MG.
Muscle relaxants. The response of the patient with
MG to muscle relaxants is difficult to predict, and
administration of these drugs should be monitored
closely with a peripheral nerve stimulator.48 The drugs
that are used to treat MG (anticholinesterases) have an
effect on the response to muscle relaxants. For example, the anticholinesterase, pyridostigmine, not only
inhibits the AChE enzyme, but also decreases plasma
cholinesterase activity. Plasma cholinesterase is responsible for degrading succinylcholine, a depolarizing neuromuscular blocker, and ester-type local anesthetics.48
In addition, patients with MG treated with pyridostigmine show a marked resistance to succinylcholine,
which causes depolarization of muscle endplates, and
this is thought to be the result of the reduced number
of AChRs at the NMJ.49 Thus, there may be prolonged
effects of anesthetic drugs from these medications.
Conversely, patients with MG are extremely sensitive to
nondepolarizing muscle relaxants (eg, curare). Studies
demonstrate the increased sensitivity to various nondepolarizing muscle relaxants (competitive antagonists)
such as atracurium50 and vecuronium.51 However, the
use of short- and intermediate-acting muscle relaxants
is acceptable with judicious titration and peripheral
nerve monitoring, with the ability to reverse their
effects at the end of surgery.52 In addition, the use of
these shorter-acting muscle relaxants may avoid the
need for reversal with anti-AChE, which can trigger a
cholinergic crisis. A cholinergic crisis is characterized
by muscle weakness and respiratory insufficiency similar to that seen with MG. It is precipitated by an excess
of the anti-AChE agent.53
Miscellaneous drugs. Certain antibiotics have been
reported to reduce neuromuscular transmission in
patients with MG and should be avoided during the
perioperative period. Aminoglycosides (streptomycin,
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AANA Journal/August 2002/Vol. 70, No. 4

kanamycin, gentamicin, neomycin, amikacin),54,55

erythromycin,56 and polymyxin B sulfate9 have all been
implicated in this action. It seems that calcium gluconate is effective in reversing this aminoglycosideinduced muscle weakness, whereas calcium chloride
partially antagonizes the neuromuscular block produced by polymyxin B.55 In addition, 2 cases have been
reported involving ciprofloxacin and increased neuromuscular blockade.57,58 There are several cardiovascular
drugs that also have demonstrated worsening of MG
and should be given with caution or avoided. Procainamide seems to potentiate MG,59 -blockers seems
to also potentiate MG because of their depressant
effects on the NMJ,60 and antiepileptic drugs, especially
phenytoin, can decrease muscle strength.9 These medications should be avoided whenever possible.

Current practice of anesthesia in MG

Preoperative care. An MG severity classification system by Osserman and Genkins (Table) has been
described: I, ocular signs and symptoms only; IIA, generalized mild muscle weakness; IIB generalized moderate
weakness and/or bulbar dysfunction; III, acute fulminating manifestations and/or respiratory dysfunction; and IV,
late, severe, generalized MG.61 This grading system can be
useful as an indication for perioperative complications.53
There is approximately a 10% incidence of other
autoimmune diseases that occur concomitantly with
MG, including hypothyroidism (10% occurrence),
rheumatoid arthritis, systemic lupus erythematous, and
pernicious anemia. It is important to optimize these
conditions before elective surgery for the patient with
MG. This includes optimizing a euthyroid state, evaluating cervical spine involvement in the patient with
rheumatoid arthritis, and relief or lessening of systemic
lupus erythematous manifestations.48,62
The respiratory status of the patient should be evaluated with spirometry, as MG affects both the inspiratory and expiratory muscles.54 Pulmonary function
Table. Myasthenia gravis severity classification system
by Osserman and Genkins61
Classification

Symptoms

Ocular signs and symptoms

IIA

Generalized mild muscle weakness

IIB

Generalized moderate weakness

and/or bulbar dysfunction

III

Acute fulminating manifestations

and/or respiratory dysfunction

IV

Late, severe, generalized myasthenia

gravis

tests show low vital capacity, normal total lung capacity, normal or elevated residual volume, and decreased
maximal inspiratory and expiratory pressures.63 However, patients with MG maintain a normal response to
carbon dioxide and an intact ventilatory drive.64 About
15% of patients with MG have thymomas that, if they
become large enough, can cause airway collapse and
occlusion at the induction of general anesthesia. These
patients should undergo chest computed tomography
and flow volume spirometry to evaluate the severity of
this mediastinal mass and the potential for tracheal
occlusion.54
A thorough cardiac assessment should be conducted, especially for conduction defects, ST and T
wave changes, and arrhythmias (bradycardia, ventricular premature contractions, atrial fibrillation) that are
observed in patients with MG. Significant arrhythmias
should be evaluated and treated by a cardiologist before
surgery.65 A small percentage of patients with MG are
reported to have myocarditis, which may be related to
MG or to an associated autoimmune disorder. These
patients demonstrate impaired left ventricular filling
that usually is reversed by an anticholinesterase.66
When symptoms of impaired cardiac function are discovered, referral to cardiology for further evaluation
(eg, echocardiography) and optimization should be
performed.
As a result of the weakened musculature of the
oropharynx, the patient with MG is at high risk for pulmonary aspiration of gastric contents.48 Therefore, it is
prudent to prophylactically administer sodium citrate
to neutralize gastric acids, a gastrointestinal prokinetic
medication (eg, metoclopramide) to increase gastric
motility, and a histamine (H2) blocker to decrease gastric acid production.48
Preoperative management goals include optimization of anticholinesterase therapy, weaning of corticosteroids to the lowest possible dose, and, if needed,
plasmapheresis to prepare the patient for surgery.53
Plasmapheresis is recommended for patients with MG
with a vital capacity of less than 2 L7 and leads to temporary remission in 45% of cases.53 However, caution
needs to be taken in administering drugs metabolized
by plasma cholinesterases, such as succinylcholine and
mivacurium, as their action may be prolonged.53
Premedication. There are varying regimens for the
administration of anticholinesterase (anti-AChE) drugs
to the patient with MG. One regimen suggests administering one half the usual morning dose for patients
with class I or II MG and the full dose for more severe
cases.67 Other anesthesiologists withhold anti-AChE
drugs on the morning of surgery in order to decrease
the dose of muscle relaxant needed.
Preoperative sedation with opioids and anxiolytics

should be used judiciously, as patients with MG have

very little respiratory reserve. There also is a high likelihood of a need for postoperative ventilatory support;
therefore, the patient should be counseled for the possibility of endotracheal tube intubation and ventilatory
support following surgery.48 The following preoperative criteria correlate with the need for postoperative
ventilatory support in the patient undergoing thymectomy: (1) disease duration greater than 6 years, (2)
presence of chronic obstructive pulmonary disease, (3)
pyridostigmine dose greater than 750 mg/per day during the 48 hours before surgery, and (4) preoperative
vital capacity less than 2.9 L.68
The anesthetic plan or management of the myasthenic patient should be individualized according to
the severity of the disease and the nature of the surgical procedure. Whenever possible, regional or local
anesthesia should be used rather than general anesthesia. However, the amount of local anesthetic may need
to be reduced, especially ester local anesthetics in a
patient receiving anticholinesterase drugs, since ester
local anesthetics are degraded by plasma cholinesterases. Furthermore, the level of block for spinal or
epidural anesthesia must be controlled closely to prevent a high thoracic block that could weaken accessory
respiratory muscles, resulting in dyspnea or acute respiratory failure.53 In addition, a combined technique of
general anesthesia and regional anesthesia (epidural
block) can provide excellent muscle relaxation without
the use of neuromuscular blockers. This has been
demonstrated in laparoscopic surgery with immediate
tracheal extubation postoperatively.69
Intraoperative care. Standard monitoring should
be used for every patient with MG undergoing surgery:
temperature, electrocardiogram, blood pressure, pulse
oximetry, in-line carbon dioxide, and ventilation rate,
and an arterial line should be inserted for obtaining
samples for blood gas analysis that can guide the timing of extubation. In addition, for a large thymoma
case, central venous access should be obtained, as the
potential for blood loss is increased.53
Induction of anesthesia with a short-acting intravenous agent is appropriate for the patient with MG;
however, one should anticipate an exaggerated respiratory depressant effect. The intubation of the trachea
usually requires the use of muscle relaxation in the
patient without MG; however, this may be accomplished without muscle relaxation by exploiting the
existing weakness and the relaxing effects of volatile
gas anesthetics on skeletal muscle.48 As an alternative,
lower doses of muscle relaxants may be used prudently.
The maintenance of anesthetic depth for surgery
often is achieved by the use of nitrous oxide and a
volatile anesthetic gas. The muscle-relaxing properties
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307

associated with volatile anesthetic gases usually reduce

or even eliminate the dose of muscle relaxants needed,
as neuromuscular transmission is reduced by about
50%.51 In addition, anesthetic gases dissipate at the end
of surgery, which allows for the evaluation of skeletal
muscle strength during the early postoperative period.
If a muscle relaxant is required, a short- or intermediate-acting nondepolarizing muscle relaxant, such as
mivacurium or vecuronium, is used with one half to
two thirds the normal dose administered. Careful monitoring with a peripheral nerve stimulator should be
conducted. Opioids are used with caution due to their
ventilatory depressant effects. Intravenous general
anesthesia with propofol also has been used successfully; it provides easy control of depth and quick recovery and avoids consequences at the NMJ.70
Postoperative care. Postoperatively, the endotracheal tube often is left in place until demonstration of
adequate levels of ventilation are observed. Good indications of the need for postoperative ventilatory support are the aforementioned preoperative criteria.
Gracey et al describe recent surgery (especially thymectomy) as the most common reason for respiratory failure in MG.71 Generally, MG classes III and IV have a
high incidence of postoperative respiratory failure. Criteria for extubation of the patient with MG are stringent and consist of an awake patient who can maintain
a head lift for more than 5 seconds and generate a sustained negative inspiratory force of more than 25 cm
H2O.52 In addition, the patients respiratory rate should
be less than 30 per minute and vital capacity more than
10 mL/kg; arterial blood gases should reflect a PaO2 of
more than 90 mm Hg, a PaCO2 of less than 50 mm Hg,
and pH more than 7.30.72 Another reason the patient
with MG may have respiratory difficulty postoperatively is bilateral vocal cord abductor weakness (stridor), and this should be evaluated.73
Postoperative analgesia can be achieved by cautious
administration of oral or parenteral opioid analgesics
or by using regional anesthesia techniques. With opioid administration, it is imperative to monitor the respiratory status of the patient with MG, as ventilatory
reserve is decreased and the patient is more prone to
respiratory depression. As an alternative, epidural narcotics provide excellent postoperative analgesia for the
patient with MG with a much lower incidence of respiratory depression.74
Furthermore, the reintroduction of the patients preoperative medications in the early postoperative period
is very important, especially the anticholinesterases. Preoperative medications must be continued as soon as possible, especially since the improvement of MG symptoms is delayed after a thymectomy.75 Efforts to optimize
preoperative respiratory function and postoperative pain

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control are effective in decreasing postoperative complications. It also is extremely important to avoid drugs
known to increase the muscle weakness of MG.

Summary
Myasthenia gravis most commonly is an acquired
autoimmune disease that is exemplified by production of
AChR antibodies. Decreased AChR numbers at the NMJ
are manifested as a decreased amplitude of endplate
potential, which is represented clinically as muscle
weakness. The AChR antibodies are present in 80% to
90% of cases and are produced by B cells in a T
celldependent manner, and a pathologic thymus is
implicated to have an important role in MG genesis and
progression. IgG and complement components are
deposited on the postsynaptic membrane, and destructive mechanisms may consist of increased degradation of
AChRs, cross-linking of AChRs, and blockage of AChRs.
Since the NMJ involves the site of action of many commonly used anesthetic drugs, anesthesia providers must
understand the pathophysiology of MG, be cognizant of
the many drug interactions that can be detrimental to the
myasthenic patient, and administer anesthetics that
would most benefit the patient with MG.
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AUTHORS
MAJ Thomas E. Ceremuga, CRNA, MSN, AN, USA, is a graduate student
in the Neuroscience Program, Uniformed Services University of the
Health Sciences, Bethesda, Md.
Xiang-Lan Yao, MD, PhD, is a research assistant professor, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Md.
Joseph T. McCabe, PhD, is a professor and vice chairman, Department of Anatomy, Physiology & Genetics, Uniformed Services University
of the Health Sciences, Bethesda, Md.

DISCLAIMER
The opinions or assertions contained herein are the private ones of the
authors and are not to be construed as official or reflecting the views of
the US Department of Defense or the Uniformed Services University of
the Health Sciences.