Case 24 - Myasthenia Gravis Flashcards

1
Q

Define Myasthenia Gravis (MG)

A

MG

  • autoimmune disease of the NMJ
  • antibodies produced and block AcH nicotinic receptor at NMJ (post-junctional receptors)
  • due to antibody blockade of AcH NMJ receptors, there is a decrease in neuromuscular transmission at motor end plate –> unable to generate a sufficient action potential to generate strong muscle contraction
  • experience weakness and fatigue of voluntary muscles, especially with use, and resolves with rest.
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2
Q

How is MG diagnosed?

A

MG is suspected from patient’s history and confirmed by clinical, electrophysiologic, immunologic, and pharmacologic testing.

Clinical

  • most common onset is ocular, with ptosis or diplopia.
  • Bulbar musculature causes difficulty breathing and swallowing

Electromyography (EMG)

  • motor nerve stimulated three times per second, decrement of response is seen

Antibody serum detection/antibody titers

Tensilon Test

  • endrophonium given (2 to 10mg) –> may elicit improvement in strength in MG suspected patients
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3
Q

How is MG classified?

A

Osserman and Genkins Classification System

Grade 1

  • Ocular muscles only,
  • EMG studies are negative of other muscles

Grade 1A

  • Ocular + peripheral
  • ocular muscle involved
  • EMG studies positive of other muscles

Grade IIA

  • Mild Generalized
  • skeletal or bulbar muscles. No resp involvement
  • good respose to drug therapy

Grade IIB

  • moderate generalized
  • severe involvement of skeletal and bulbar muscle
  • dysphagia, difficulty chewing. No resp involvement
  • fair respone to drug therapy

Grade III

  • Acute fulminating
  • rapid onset of severe bulbar and skeletal weakness
  • Resp muscles involved
  • poor response to drug therapy

Grade IV

  • Late Severe
  • Severe MG 2 years after onset of symp
  • poor prognosis.
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4
Q

TX for MG?

A

Tx of MG involves ACH-I, immunosuppressant therapy, plasmapheresis/plasma exchange, thymectomy.

ACH-I

  • inhibit acetylcholinesterase enzyme at NMJ, therby increasing AcH concentration –> agonist-receptor interaction is more sucessful
  • Pyridostigmine - long acting, few musarinc SE
  • Overdose can cause cholinergic crisis

Immunosuppressants

  • steroids, immunosuppressive agents
  • steroids SE = osteoperosis, HTN, ulcers

Plasmapheresis/plasma exchange

  • reserved for severe MG (resp failure)
  • can decrease plasma cholinesterases –> prolong effect of Sux/ester LA/ mivacurium

Thymectomy

  • common to have abnormal thymus gland
  • tx of choice for most MG patients
  • best performed within first 3 yrs of dx
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5
Q

Why is MG sensitive to nondepolarizing muscle relaxants (NMBDs)?

A

AcH receptors are each acivated by two AcH molecules.

activation of receptors cause a small electrical current across membrane of motor end plate. Summation of small current (via activation of many receptors) result in depolarization and action potential generation in muscle cell to result in muscle contraction

NMBDs competively block AcH receptors.

MG patients already have pre-existing AcH receptors blocked by autoantibodies from the disease, therefore they are already weak. Only small amounts of NMBD are needed to intefere with neuromuscular transmission.

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6
Q

Why is MG resistent to succinylcholine (SUX)?

A

Succinylcholine is an agnoist at acetylcholine receptors.

MOA = First causes depolarization of motor end plate and then prevents rapid repolarization.

Sux can only work if enough receptors are bound in order to cause depolarization.

MG patients have smaller number of AcH receptors available due to antibodies blocking the receptors.

Larger doses of SUX is required to compete with the autoantibodies and activate this limited number of available AcH receptors

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7
Q

Why is SUX prolonged in MG patients?

A

MG patients are usually on ACH-I, which also inhibit plasma cholinesterases.

MG patients that undergo plasmapharesis / plasma exchange also have decreased plasma cholinesterase concentration.

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8
Q

How is a patient with MG optimized for surgery?

A
  1. optimize medical and emotional states before surgery
  2. hx of resp disease or bulbar involvement –> consider PFT. Patients should be informed of potential postop intubation and ventilation
  3. premed with caution, avoid in patients with resp difficulty
  4. continue steroids in periop period
  5. ACH-I continuation is controversial –> can antagnoize NMBDs (competiting AcH at NMJ with NMBD) and prolong SUX duration of action. Patients may be physically or psychologically dependent on them.
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9
Q

Describe an appropriate anesthetic technique for pts with MG undergoing transcervical thymectomy

A
  1. Place ASA stand monitors. invasive monitors based on history and physical (resp difficulty, consider a line for ABGs).
  2. denitrogenation with 100% oxygen, induce with propofol, etomidate, or ketamine.
  3. tracheal intubation can readily be achieved with potent inhaled anesthetic since patients have pre-existing weakness due to autoimmune disease. These patients are more sensitive to the neuromuscular depressent effects of volatile anes.
  4. patients that cannot tolerate the cardiovascular depression associated with potent inhaled anes may require small incremental doses of intermediate acting NMBD or balanced anes with opioid infusion (remi)
    • ​​Use peripheral nerve stimulation monitoring when using NMBDs**
  5. Cis-atr is an option since it has shorter half life, small volume of distribution, clearance via Hofmann Elimination (pH and temp).
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10
Q

What are considerations in a patient with MG who requires RSI?

A
  • MG patients presenting for emergent surgery may require RSI due to increased risk of Aspiration.
  • MG patients show resistence to SUX secondary to AcH nicotinic receptors blocked by antibodies
    • *SUX works by acting as an agonist and binding to these receptors to faciliate depolarization followed by preventing rapid repolarization. *
  • 1) Higher dose of SUX may be needed for RSI. Of note 1 to 1.5 mg/kg is an RSI dose for normal patients, but this is also 3.5 x ED95. Therefore this dose will work in MG patients as well.*
    2) Patients on ACH-I or s/p plasmapheresis will experience prolong duration of SUX due to decrease plasma cholinesterase levels.
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11
Q

can you use rocornium for RSI, and what may the considerations?

A
  • rocornium works by competitive inhibiton of nictonic cholinergic receptors at postsynaptic terminal of NMJ
  • less dose required in MG pts since autoantibodies are antagonizing AcH receptors at postsynap terminal as well
  • giving NMBD can potentiate resp difficulty/distress post-op if pt has pre-existing resp insuffiency
    • can occur despite reversal
    • will be a confounding variable for an MG pt with post-op resp failure
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12
Q

How is adequacy of strength assessed in MG patients emerging from anesthesia prior to extubation?

A
  • MG patients usually exhibit muscular weakness due to the disease process.
  • weakness on emergence should not be assumed to be weak due to residual neuromuscular blockade.

Consider preop measure of strengths as baseline exam. Consider TOF or EMG or tetanic stimulation prior to administering neuromuscular blocking agents.

Extubation Criteria

consider awake extubation in MG pts due to pre-existing muscle weakness

CVS

  • HD stable?
  • uneventful OR course/concern for airway swelling?

Neuro

  • following commands

Residual NMBD

  • sustained tetanic stimulation at 50Hz for 5 sec
  • head lift 5 sec (33% AcH receptor occupied)
  • TOF ratio > 0.9

Resp status

  • NIF of at least - 20 cm H2O (50% AcH receptors occupied)
  • TV > 6 mL/kg
  • VC > 15 mL/kg
  • Fio2 < 0.4 with adeqaute SaO2
  • PaCo2 < 55 / RR < 25
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13
Q

Why is it important to assess for adequate muscle strength prior to extubation in MG patients?

A

These patients exhibit muscular weakness due to their disease. You want to assess muscular strength using different measures as surrogates of determining diaphram and laryngeal muscle strength.

Overall, you want these patients to have enough strength to cough and clear secretions –> therefore they will a protective mechanism for aspiration (gag reflex), prevent post-op respiratory failure (clear secretions, prevent atelectasis)

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14
Q

What are other factors that augment Nondepolarizing neuromuscular blockade?

A

MG patients who demonstrate residual weakness on emergence from anesthesia shold not automatically be assumed to have residual blockade with muscle relaxant.

Factors that augment NMBD

  • Acid-base alteration
    • resp acidosis/metabo acidosis
  • electrolyte imbalance
    • hypo Mg 2+, K+, Ca 2+, Na+
  • volatile anesthetics
  • Local Anesthetics
  • Class 1A antiarrhythmics
    • Quinidine, procainamide
  • ABX
    • aminoglycosides (gentamicin, streptomycin, neomycin)
  • CCB
  • Dantrolene
  • Hypothermia
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15
Q

What is the difference between cholinergic crisis and myasthenic crisis?

A

Crisis = acute onset of muscle weakness in MG patients.

Cholinergic Crisis

  • excess AcH at nicotinic and muscarinic receptors leading to increase cholinergic activity
  • due to excess ACH-I administration
  • DUMBELLS s/sx - n/v, lacrimnation, bradycardia, salvation, diarrhea/GI motility dysfunction, wheezing
  • resp weakness –> resp failure

Myasthenic Crisis

  • not enough AcH to bind to its post junctional receptors, resulting in failure of neuromuscular transmission.
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16
Q

What can be done to differentiate cholinergic crisis from myasthenic crisis?

A

both manifest with muscle weakness in MG patients

1) check pupil size

  • cholinergic crisis has miosis
  • myasthenic crisis has mydriasis

2) Endrophonium (tensilon) challenge test

  • give 2 to 10 mg of endrophonium (ACH-I)
  • myasthetnic crisis patients symptoms improve
  • cholinergic crisis patients symptoms worsen.

Tx cholinergic crisis with anticholinergic (atropine/glyco)

17
Q

Can the need for postop ventilation be predicted preoperatively?

A

Patients with MG are increased firsk for prolonged postop ventilation

Historically, in patients undergoing transsternal thymectomy, the following were predictors for postop ventilation:

  • MG duration > 6 yrs
  • pyridostigmine dose > 750 mg/day
  • preop VC < 2.9 L

This is not seen in patinets with transcervical thymectomy.

for high risk patients, preop plasma exchange or high dose perioperative steroid therapy can reduce probability of resp failure.