jcourse3_0802_p301-310

*6 CE Credits

AANA Journal Course 3

*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.

Update for nurse anesthetists

Etiology, mechanisms, and anesthesia implicationsof autoimmunemyasthenia gravisMAJ Thomas E. Ceremuga, CRNA, MSN, AN, USAXiang-Lan Yao, MD, PhDJoseph T. McCabe, PhDBethesda, Maryland

ObjectivesAt the conclusion of this course, the reader should beable to:

1. Discuss the pathologic processes related to theneuromuscular junction in autoimmune myas-thenia gravis.

2. Identify the cellular autoimmune events occur-ring in myasthenia gravis.

3. Describe the various modalities used in the treat-ment of myasthenia gravis.

4. Identify the pharmacologic agents that reduceneuromuscular transmission in patients withmyasthenia gravis and should be avoided in theperioperative period.

5. Discuss the prudent delivery of anesthesia and theanesthetic plan for patients with myastheniagravis.

IntroductionMyasthenia gravis (MG) is the prototypical neurologi-cal autoimmune disease. Willis first described the mal-ady in 1672, but it was not until 1895 that Jolly usedthe name, myasthenia gravis.1 Jolly described a condi-tion of 2 boys who exhibited muscle weakness that pro-gressively worsened on repetition but improved withrest.1 Muscle weakness and fatigability arise fromdefective or decreased acetylcholine receptors (AChRs)at the neuromuscular junctions (NMJs), where nervesignals from spinal motor neurons that innervate mus-cles cannot effectively induce muscle contraction.

Various mechanisms of pathogenesis lead to the MGsyndrome. Congenital myasthenias are caused by avariety of genetic defects (eg, ion channels or subunitsof AChR mutations) of the presynaptic or postsynapticmachinery of the NMJ.2 Lambert-Eaton myasthenic syn-

AANA Journal/August 2002/Vol. 70, No. 4 301

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 junc-

tions, where nerve signals from spinal motor neurons that

innervate muscles cannot effectively induce muscle contrac-

tion. Several mechanisms of pathogenesis lead to the MG syn-

drome. The most prevalent cause of MG is an autoimmune dis-

order in which the patient produces antibodies that attack the

nicotinic acetylcholine receptor at the neuromuscular junction.Anesthesia management of the patient with MG is challengingand requires specific management; however, safe and success-ful outcomes are achievable. This course emphasizes theautoimmune neuromuscular defect in MG, current treatmentsfor this syndrome, contraindications of certain anestheticdrugs in this condition, and anesthetic management of apatient with MG in the operating room environment.

Key words: Acetylcholine receptor, autoimmune disease, myas-thenia gravis, receptor, neuromuscular junction.

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

drome frequently is associated with neoplasms andinvolves a dysregulation of presynaptic acetylcholine(ACh) release. It seems that the presynaptic defectinvolves an alteration in calcium channels and, conse-quently, decreased release of acetylcholine into thesynapse.3,4 The most common cause of MG is anautoimmune disorder in which the patient producesantibodies that attack the nicotinic acetylcholine recep-tor at the NMJ.5 This article emphasizes the autoim-mune neuromuscular defect in MG, current therapy forthis syndrome, contraindications of certain anestheticdrugs in this condition, and anesthetic management ofa patient with MG in the operating room environment.

History and review of the literature Autoimmune neuromuscular MG. The hallmark

features of autoimmune MG are fatigue, increasingweakness with repetitive motion, and a higher inci-dence in women.6 Characteristics and symptoms of MGreflect the dysfunctional AChR at the NMJ, includinggeneralized weakness in 85% of patients and limitedweakness of ocular muscles in 15% of patients withocular MG.7 While ocular MG is less prevalent, ocularmuscle problems, such as ptosis or diplopia, usually arethe initial complaint, with subsequent progression tothe generalized disease.8 Patients with generalized MGcomplain of dysphagia, dysphonia, proximal limb mus-cle weakness, and even exacerbation to dyspnea or ven-tilatory failure (myasthenic crisis).9 In 85% to 95% ofpatients with MG, a thymic abnormality, such as thy-moma or thymic hyperplasia, may be responsible forsecretion of AChR antibodies.10

Diagnostic testing for MG includes pharmacologic,electrophysiologic, and laboratory testing. Edropho-nium, an anticholinesterase (anti-AChE), is adminis-tered to inhibit the enzyme that degrades ACh; there-fore, more ACh remains at the synapse. The patientwith MG (Figure 1) usually demonstrates a temporaryreversal of muscle weakness with edrophonium.11

Nerve conduction tests, such as repetitive nerve stimu-lation, also are performed to verify the MG diagnosis.Motor response is monitored after the nerve is stimu-lated repetitively at the rate of 2 Hz, and the patientwith MG usually exhibits a gradual decrease in ampli-tude.12 In addition, serum AChR antibodies are assayedto confirm the diagnosis; results for 90% to 95% ofpatients with MG are positive.10 The positive resultsfrom these testing modalities point to a defect in theNMJ in the patient with MG.

The neuromuscular junction. Proper functioning ofthe NMJ is required for impulse propagation and mus-cle contraction. The NMJ is a complex structure, com-posed of the motor nerve terminal, postsynaptic mus-cle surface, and specialized basal lamina (Figure 2).

Nerve terminal endings are located presynaptically inthe primary synaptic clefts at the synapse. The musclesurface area, postsynaptically, is enlarged by invagina-tions of the plasma membrane into secondary synapticfolds. The AChRs are located primarily at the distalextents of the folds, in closer apposition to the nerveterminals.6 There is continual AChR turnover, in whichold receptors are internalized and degraded, and newreceptors are synthesized and inserted into the synapticfolds.6 Skeletal muscle sodium channels are located inthe depths of the folds, and AChE, the enzyme thathydrolyzes ACh, is located at the basal lamina of thesecondary synaptic fold.6

The generation of a muscle action potential and,ultimately, muscle contraction begins with the depolar-ization of the presynaptic nerve terminal. This leads tocalcium influx via channels and calcium-dependentfusion of synaptic vesicles with presynaptic nerve ter-minal membrane in the nerve boutons. Fusion allowsthe release of ACh into the synapse, where the neuro-transmitter then can diffuse across the synaptic cleftand bind to AChRs. If a large enough quantity of AChis released, a muscle endplate potential is reached,resulting in postsynaptic depolarization and musclecontraction. ACh is removed by AChE hydrolysis andby diffusion.6

Adult human AChR (Figure 3) is part of a super-family of neurotransmitter-gated ion channels, and itspentameric (5-subunit) structure includes 2 and 1each of the , , and subunits. Fetal AChR is similar,except a subunit is substituted for the subunit.13,14The fetal AChR is retained in adult thymic myoidcells15 and adult ocular muscle fibers.16 The adultAChR subunits (see Figure 3) are believed to bearranged around a central ion channel in the following

Figure 1. Edrophonium test

(A) Patient with myasthenia gravis with ptosis(B) Patient after receiving 10 mg of edrophonium

(From Pourmand.12

Reproduced by permission of Mosby, Inc.)

order: 111.17 The ACh binding sites are formedat the union of the 1 and and the 1 and sub-units.18 Both binding sites must be occupied by an ago-nist (ACh) for the ion channel to open.19 The bindingof ACh to both sites results in a conformational changein the AChR and channel opening.14 Conversely, if anantagonist (eg, vecuronium) binds one site, channelopening is prevented.18

Autoimmune pathology. A region located on theextracellular tip of the 1 subunits has been describedas the main immunogenic region. Since the mainimmunogenic regions are located at the outer (extra-cellular) portion of the AChR, they are easily recog-nized by antibodies.20 A single antibody is unable tocross-link 2 1 subunits but easily cross-links (Figure

4) 2 adjacent AChRs.21 These properties and character-istics of the main immunogenic region facilitate thepathogenic mechanisms involved in the autoimmuneresponse to AChRs.18

The evidence that links AChR antibodies as thecausative factor in MG includes the following: (1) Ofpatients with MG symptoms, 85% have these antibod-ies.10 (2) Immunoglobulin G (IgG) has been found atthe neuromuscular endplate.22 (3) Plasmapheresis toreduce circulating antibodies provides temporarysymptomatic relief.23 (4) Healthy animals injected withantibodies against AChR produce MG signs.24 Therealso is the possibility that the antibodies bind to or nearthe ligand-binding site.7 Antibodies also can cross-linkAChRs resulting in internalization, increased degrada-


Axon

Mitochondria

Vesicle

Acetylcholine

Acetylcholinereceptor

Acetylcholinesterase

Basal lamina

ANerve

terminal

Release site

Muscle(end-plate)

Figure 2. Normal human neuromuscular junction

(From Pourmand.12


Muscle AChRs Subunits: 1, 1, , ,

Fetal form Adult form

ACh binding siteat subunit interface

(1) 12(1) 12

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

(From Lindstrom.18

Reproduced by permission of John Wiley & Sons, Inc.)


tion rate, and a decrease in AChR density at the end-plate. This increase in AChR degradation correlateswell with clinical manifestations of MG.25

Moreover, complement-mediated destruction of theNMJ occurs as a result of AChR antibodies. Antibodiesbind to the C9 component of complement (part of theimmune system involved in cell destruction), trigger-ing an inflammatory cell response, endplate membranedegradation, and destruction of junctional folds thatharbor AChR-abundant membranes (Figure 5). Thisinevitably would reduce the membrane surface avail-able for AChR insertion.26 Therefore, the autoimmuneresponse in MG affects many components of themachinery at the postsynaptic membrane, resulting inaltered depolarization of muscle tissue.

Morphological studies of the NMJ in MG demon-strate the following postsynaptic anomalies (Figure 6):decreased quantity of AChR,27 widened and decreasedmachinery of the postsynaptic fold, and increased gapbetween presynaptic and postsynaptic membranes.28

Therefore, the primary pathologic mechanism of MG isa reduction in AChRs and, thus, a reduction in the end-plate potential that is not strong enough to reachthreshold potential, depolarization of muscle mem-brane, and resultant muscle contraction.12 If this trans-mission failure occurs at many junctions, the strengthof the muscle contraction is reduced and the patientbecomes weak. Normally, only 25% to 30% of AChRsare necessary for neuromuscular transmission. Theremaining 70% to 75% of receptors represent a safetymargin.29 In MG, there is a decrease in the number offunctional AChR and a decrease in the safety margin.

Cellular autoimmunity mechanisms. The precipi-tating events that cause MG are not completely under-stood, but evidence implicates the thymus, as alteredthymic function has a 90% prevalence in this disease.30

For example, thymoma or hyperplasia of the thymusoccurs in high frequency in patients with MG, T and Bcells have an active role in antibody formation, myoidcells of the thymus gland have the same type of surfaceas AChR, and thymectomies usually are beneficial for

patients with MG.12 There seem to be different triggermechanisms of autoimmunity for the various forms ofMG. The patient with rheumatoid arthritis may triggeran MG syndrome by taking penicillamine, which isbelieved to react covalently with AChRs, producingnew antigenic sites.31 This MG condition is reversiblewith the termination of penicillamine. A paraneoplasticimmune response may account for the 12% of patientswith MG who have a thymoma, for they have differentHLA marker frequencies than do other patients withMG. This indicates a probable difference in immunesystem genetic background.32 They have not only highlevels of AChR antibodies, but also antibodies to sev-eral muscle proteins in the interior of the cells.33 Inmost MG cases, the immunogen is likely the nativemuscle AChR or a closely related protein. The fetal type( subunit) has been implicated as the immunogen, asselective reaction with fetal AChRs has been reportedwith antibodies from patients with MG.34

Molecular mimicry by microbes also has been sug-gested to be responsible for the autoimmune responsein MG, in which bacterial or viral proteins initiate theimmune response, then reaction with the AChR leadsto epitope (antigenic determinant) spreading. In addi-tion, both bacteria and viruses can express superanti-gens that nonspecifically activate many T and B cells.18

Although the B cells synthesize the autoantibodies toAChR, there is evidence for a T-cell role in autoimmu-nity,35 as T cells from patients with MG seem torespond to AChR stimulation and aid in the productionof AChR antibodies.36 Helper T cells found in patientswith MG can increase the synthesis of anti-AChR anti-bodies. In MG, T-helper lymphocytes are required tocooperate with B lymphocytes in promoting autoanti-body synthesis.37 The autoantibodies in MG are poly-clonal and heterogeneous and recognized different epi-topes on the AChR.38,39

State of the art Treatment of MG. Treatment modalities usually

reflect the rate of progression, severity, and weakness

Extracellular

TransmembraneCytoplasmic

AChRs cross-linkedby antibody to the MIR

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

(From Lindstrom.18

Reproduced by permission of John Wiley & Sons, Inc.)

distribution of the patient. Age, sex, and the presenceof concomitant diseases also influence long-term ther-apy decisions. In general, the treatment for MG consistsof 5 modalities: anticholinesterase drugs, immunosup-pressants, thymectomy, plasmapheresis, and intra-venous immunoglobulins (IgG).40

Anticholinesterases usually are the initial therapyand provide symptomatic improvement in muscularstrength, as they inhibit the enzyme that degrades ACh.This allows ACh to remain longer at the NMJ, increas-ing the probability for ACh binding to AChRs.Immunosuppressant drugs (eg, corticosteroids, aza-thioprine, and cyclosporine) are administered todecrease the immune response and modulate mecha-nisms in cellular immunity.40 Since thymic abnormali-ties (hyperplastic changes and neoplasias) are prevalentand evidence suggests they are intricately involved inmany forms of MG, surgical thymectomies are also per-formed.41 As mentioned previously, it is hypothesized

that autoreactive T cells are activated in the thymus.42

Studies indicate that thymectomies decrease T-cell reac-tivity against disease-specific antigens and providesymptomatic relief .43 In addition, if the source of theimmunogen is thymic myoid cells, their eliminationmay decrease the immune response44 as a possiblereservoir of AChR antibody-producing B cells may beremoved with this operation.45 Plasmapheresis usuallyis used as a short-term treatment in patients withextreme weakness. This treatment is believed toremove circulating AChR antibodies and immune com-plexes, often resulting in rapid improvement, whichlasts 6 to 8 weeks.40

In addition to plasmapheresis, intravenous immu-noglobulins (IgG) have been used in the extremelyweakened patient with acute MG. The mechanism bywhich IgG improves MG symptoms is unclear but isspeculated to involve the interaction between autoanti-bodies and anti-idiotypic (nonspecific) antibodies in


Figure 5. (A) Normal neuromuscular junction: arrow is synaptic cleft, asterisk is the secondary cleft. (B) Lytic C9complement component of myasthenic neuromuscular junction showing synaptic degeneration; asterisk is thejunctional folds without nerve terminal and arrrow is presynaptic staining.

(From Pourmand.12


A B

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

AChR = acetylcholine receptor

(From Pourmand.12



IgG preparations.46 Future treatment modalities arebeing considered with a more cell-directed approach,such as monoclonal antibodies directed against helperT cells and administration of immunotoxins that woulddestroy B cells specific for AChRs.7,47

Anesthesia pharmacology contraindications. Thehallmark symptom of muscle weakness, especially afterrepetitive stimuli, can lead to dangerous and life-threat-ening situations for the patient with MG. One suchenvironment or condition is surgery (often an electivethymectomy) and, more important, the administrationof anesthesia during the surgical procedure. MG is acondition of particular interest to anesthesia as itinvolves the NMJ, the site of action of many commonlyused anesthetic drugs. There are many pharmacologicagents used in anesthesia that can lead to devastatingconsequences and even precipitate a myasthenic crisisin the patient with MG.

Muscle relaxants. The response of the patient withMG to muscle relaxants is difficult to predict, andadministration of these drugs should be monitoredclosely with a peripheral nerve stimulator.48 The drugsthat are used to treat MG (anticholinesterases) have aneffect on the response to muscle relaxants. For exam-ple, the anticholinesterase, pyridostigmine, not onlyinhibits the AChE enzyme, but also decreases plasmacholinesterase activity. Plasma cholinesterase is respon-sible for degrading succinylcholine, a depolarizing neu-romuscular blocker, and ester-type local anesthetics.48

In addition, patients with MG treated with pyridostig-mine show a marked resistance to succinylcholine,which causes depolarization of muscle endplates, andthis is thought to be the result of the reduced numberof AChRs at the NMJ.49 Thus, there may be prolongedeffects of anesthetic drugs from these medications.Conversely, patients with MG are extremely sensitive tonondepolarizing muscle relaxants (eg, curare). Studiesdemonstrate the increased sensitivity to various nonde-polarizing muscle relaxants (competitive antagonists)such as atracurium50 and vecuronium.51 However, theuse of short- and intermediate-acting muscle relaxantsis acceptable with judicious titration and peripheralnerve monitoring, with the ability to reverse theireffects at the end of surgery.52 In addition, the use ofthese shorter-acting muscle relaxants may avoid theneed for reversal with anti-AChE, which can trigger acholinergic crisis. A cholinergic crisis is characterizedby muscle weakness and respiratory insufficiency sim-ilar to that seen with MG. It is precipitated by an excessof the anti-AChE agent.53

Miscellaneous drugs. Certain antibiotics have beenreported to reduce neuromuscular transmission inpatients with MG and should be avoided during theperioperative period. Aminoglycosides (streptomycin,

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

erythromycin,56 and polymyxin B sulfate9 have all beenimplicated in this action. It seems that calcium glu-conate is effective in reversing this aminoglycoside-induced muscle weakness, whereas calcium chloridepartially antagonizes the neuromuscular block pro-duced by polymyxin B.55 In addition, 2 cases have beenreported involving ciprofloxacin and increased neuro-muscular blockade.57,58 There are several cardiovasculardrugs that also have demonstrated worsening of MGand should be given with caution or avoided. Pro-cainamide seems to potentiate MG,59 -blockers seemsto also potentiate MG because of their depressanteffects on the NMJ,60 and antiepileptic drugs, especiallyphenytoin, can decrease muscle strength.9 These med-ications should be avoided whenever possible.

Current practice of anesthesia in MG Preoperative care. An MG severity classification sys-

tem by Osserman and Genkins (Table) has beendescribed: I, ocular signs and symptoms only; IIA, gener-alized mild muscle weakness; IIB generalized moderateweakness and/or bulbar dysfunction; III, acute fulminat-ing manifestations and/or respiratory dysfunction; and IV,late, severe, generalized MG.61 This grading system can beuseful as an indication for perioperative complications.53

There is approximately a 10% incidence of otherautoimmune diseases that occur concomitantly withMG, including hypothyroidism (10% occurrence),rheumatoid arthritis, systemic lupus erythematous, andpernicious anemia. It is important to optimize theseconditions before elective surgery for the patient withMG. This includes optimizing a euthyroid state, evalu-ating cervical spine involvement in the patient withrheumatoid arthritis, and relief or lessening of systemiclupus erythematous manifestations.48,62

The respiratory status of the patient should be eval-uated with spirometry, as MG affects both the inspira-tory and expiratory muscles.54 Pulmonary function

Classification Symptoms

I Ocular signs and symptoms

IIA Generalized mild muscle weakness

IIB Generalized moderate weaknessand/or bulbar dysfunction

III Acute fulminating manifestationsand/or respiratory dysfunction

IV Late, severe, generalized myastheniagravis

Table.Myasthenia gravis severity classification systemby Osserman and Genkins61

tests show low vital capacity, normal total lung capac-ity, normal or elevated residual volume, and decreasedmaximal inspiratory and expiratory pressures.63 How-ever, patients with MG maintain a normal response tocarbon dioxide and an intact ventilatory drive.64 About15% of patients with MG have thymomas that, if theybecome large enough, can cause airway collapse andocclusion at the induction of general anesthesia. Thesepatients should undergo chest computed tomographyand flow volume spirometry to evaluate the severity ofthis mediastinal mass and the potential for trachealocclusion.54

A thorough cardiac assessment should be con-ducted, especially for conduction defects, ST and Twave changes, and arrhythmias (bradycardia, ventricu-lar premature contractions, atrial fibrillation) that areobserved in patients with MG. Significant arrhythmiasshould be evaluated and treated by a cardiologist beforesurgery.65 A small percentage of patients with MG arereported to have myocarditis, which may be related toMG or to an associated autoimmune disorder. Thesepatients demonstrate impaired left ventricular fillingthat usually is reversed by an anticholinesterase.66

When symptoms of impaired cardiac function are dis-covered, referral to cardiology for further evaluation(eg, echocardiography) and optimization should beperformed.

As a result of the weakened musculature of theoropharynx, the patient with MG is at high risk for pul-monary aspiration of gastric contents.48 Therefore, it isprudent to prophylactically administer sodium citrateto neutralize gastric acids, a gastrointestinal prokineticmedication (eg, metoclopramide) to increase gastricmotility, and a histamine (H2) blocker to decrease gas-tric acid production.48

Preoperative management goals include optimiza-tion of anticholinesterase therapy, weaning of corticos-teroids to the lowest possible dose, and, if needed,plasmapheresis to prepare the patient for surgery.53

Plasmapheresis is recommended for patients with MGwith a vital capacity of less than 2 L7 and leads to tem-porary remission in 45% of cases.53 However, cautionneeds to be taken in administering drugs metabolizedby plasma cholinesterases, such as succinylcholine andmivacurium, as their action may be prolonged.53

Premedication. There are varying regimens for theadministration of anticholinesterase (anti-AChE) drugsto the patient with MG. One regimen suggests admin-istering one half the usual morning dose for patientswith class I or II MG and the full dose for more severecases.67 Other anesthesiologists withhold anti-AChEdrugs on the morning of surgery in order to decreasethe dose of muscle relaxant needed.

Preoperative sedation with opioids and anxiolytics

should be used judiciously, as patients with MG havevery little respiratory reserve. There also is a high like-lihood of a need for postoperative ventilatory support;therefore, the patient should be counseled for the pos-sibility of endotracheal tube intubation and ventilatorysupport following surgery.48 The following preopera-tive criteria correlate with the need for postoperativeventilatory support in the patient undergoing thymec-tomy: (1) disease duration greater than 6 years, (2)presence of chronic obstructive pulmonary disease, (3)pyridostigmine dose greater than 750 mg/per day dur-ing the 48 hours before surgery, and (4) preoperativevital capacity less than 2.9 L.68

The anesthetic plan or management of the myas-thenic patient should be individualized according tothe severity of the disease and the nature of the surgi-cal procedure. Whenever possible, regional or localanesthesia should be used rather than general anesthe-sia. However, the amount of local anesthetic may needto be reduced, especially ester local anesthetics in apatient receiving anticholinesterase drugs, since esterlocal anesthetics are degraded by plasma cholin-esterases. Furthermore, the level of block for spinal orepidural anesthesia must be controlled closely to pre-vent a high thoracic block that could weaken accessoryrespiratory muscles, resulting in dyspnea or acute res-piratory failure.53 In addition, a combined technique ofgeneral anesthesia and regional anesthesia (epiduralblock) can provide excellent muscle relaxation withoutthe use of neuromuscular blockers. This has beendemonstrated in laparoscopic surgery with immediatetracheal extubation postoperatively.69

Intraoperative care. Standard monitoring shouldbe used for every patient with MG undergoing surgery:temperature, electrocardiogram, blood pressure, pulseoximetry, in-line carbon dioxide, and ventilation rate,and an arterial line should be inserted for obtainingsamples for blood gas analysis that can guide the tim-ing of extubation. In addition, for a large thymomacase, central venous access should be obtained, as thepotential for blood loss is increased.53

Induction of anesthesia with a short-acting intra-venous agent is appropriate for the patient with MG;however, one should anticipate an exaggerated respira-tory depressant effect. The intubation of the tracheausually requires the use of muscle relaxation in thepatient without MG; however, this may be accom-plished without muscle relaxation by exploiting theexisting weakness and the relaxing effects of volatilegas anesthetics on skeletal muscle.48 As an alternative,lower doses of muscle relaxants may be used prudently.

The maintenance of anesthetic depth for surgeryoften is achieved by the use of nitrous oxide and avolatile anesthetic gas. The muscle-relaxing properties



associated with volatile anesthetic gases usually reduceor even eliminate the dose of muscle relaxants needed,as neuromuscular transmission is reduced by about50%.51 In addition, anesthetic gases dissipate at the endof surgery, which allows for the evaluation of skeletalmuscle strength during the early postoperative period.If a muscle relaxant is required, a short- or intermedi-ate-acting nondepolarizing muscle relaxant, such asmivacurium or vecuronium, is used with one half totwo thirds the normal dose administered. Careful mon-itoring with a peripheral nerve stimulator should beconducted. Opioids are used with caution due to theirventilatory depressant effects. Intravenous generalanesthesia with propofol also has been used success-fully; it provides easy control of depth and quick recov-ery and avoids consequences at the NMJ.70

Postoperative care. Postoperatively, the endotra-cheal tube often is left in place until demonstration ofadequate levels of ventilation are observed. Good indi-cations of the need for postoperative ventilatory sup-port are the aforementioned preoperative criteria.Gracey et al describe recent surgery (especially thymec-tomy) as the most common reason for respiratory fail-ure in MG.71 Generally, MG classes III and IV have ahigh incidence of postoperative respiratory failure. Cri-teria for extubation of the patient with MG are strin-gent and consist of an awake patient who can maintaina head lift for more than 5 seconds and generate a sus-tained negative inspiratory force of more than 25 cmH2O.

52 In addition, the patients respiratory rate shouldbe less than 30 per minute and vital capacity more than10 mL/kg; arterial blood gases should reflect a PaO2 ofmore than 90 mm Hg, a PaCO2 of less than 50 mm Hg,and pH more than 7.30.72 Another reason the patientwith MG may have respiratory difficulty postopera-tively is bilateral vocal cord abductor weakness (stri-dor), and this should be evaluated.73

Postoperative analgesia can be achieved by cautiousadministration of oral or parenteral opioid analgesicsor by using regional anesthesia techniques. With opi-oid administration, it is imperative to monitor the res-piratory status of the patient with MG, as ventilatoryreserve is decreased and the patient is more prone torespiratory depression. As an alternative, epidural nar-cotics provide excellent postoperative analgesia for thepatient with MG with a much lower incidence of respi-ratory depression.74

Furthermore, the reintroduction of the patients pre-operative medications in the early postoperative periodis very important, especially the anticholinesterases. Pre-operative medications must be continued as soon as pos-sible, especially since the improvement of MG symp-toms is delayed after a thymectomy.75 Efforts to optimizepreoperative respiratory function and postoperative pain

control are effective in decreasing postoperative compli-cations. It also is extremely important to avoid drugsknown to increase the muscle weakness of MG.

SummaryMyasthenia gravis most commonly is an acquiredautoimmune disease that is exemplified by production ofAChR antibodies. Decreased AChR numbers at the NMJare manifested as a decreased amplitude of endplatepotential, which is represented clinically as muscleweakness. The AChR antibodies are present in 80% to90% of cases and are produced by B cells in a Tcelldependent manner, and a pathologic thymus isimplicated to have an important role in MG genesis andprogression. IgG and complement components aredeposited on the postsynaptic membrane, and destruc-tive mechanisms may consist of increased degradation ofAChRs, cross-linking of AChRs, and blockage of AChRs.Since the NMJ involves the site of action of many com-monly used anesthetic drugs, anesthesia providers mustunderstand the pathophysiology of MG, be cognizant ofthe many drug interactions that can be detrimental to themyasthenic patient, and administer anesthetics thatwould most benefit the patient with MG.

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AUTHORSMAJ Thomas E. Ceremuga, CRNA, MSN, AN, USA, is a graduate studentin the Neuroscience Program, Uniformed Services University of theHealth Sciences, Bethesda, Md.

Xiang-Lan Yao, MD, PhD, is a research assistant professor, Depart-ment of Anatomy, Physiology and Genetics, Uniformed Services Univer-sity of the Health Sciences, Bethesda, Md.

Joseph T. McCabe, PhD, is a professor and vice chairman, Depart-ment of Anatomy, Physiology & Genetics, Uniformed Services Universityof the Health Sciences, Bethesda, Md.

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

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