NEURO ANESTHESIA

Myasthenia Gravis

Prof. DR. Osama Zayed

Ain Shams University
 What is Myasthenia Gravis?

• MG is an autoimmune disorder of the neuromuscular junction.

• Typically, MG manifests as a fluctuating, painless weakness and easy
fatigability of voluntary muscles.
• Weakness resolves with rest.
• Onset is slow & insidious
• It is associated with relapses and remissions.
• The incidence of MG is approximately:
 1 in 30,000 adults
 1 in 200,000 children and adolescents.
• Peak incidence occurs in the third decade of life for women and the
fifth decade for men, but may affect any age.
 What is Myasthenia Gravis?

• In MG, antibodies are produced to the acetylcholine (nicotinic)

receptor of the neuromuscular junction.
• Consequently, patients with MG have:
1. Fewer 70% to 80% usable postsynaptic acetylcholine receptors at the
end plates of affected muscles,
2. Fewer folds & Widened synaptic clefts.
• The amount of presynaptic acetylcholine released is normal or
increased.
• In normal person with a normal number of acetylcholine
receptors, only 25% to 30% of the receptors are required for
normal neuromuscular transmission; this is termed as the
“margin of safety” in neuromuscular transmission.
• In patients with MG, the margin of safety is decreased.
 Diagnosis of Myasthenia Gravis

A. Clinical:
• The most common onset is ocular muscle group with ptosis or
diplopia.
• If the disease remains localized to the eyes for 2 years, there is
a low likelihood of progression to generalized MG.
• Involvement of bulbar musculature predisposes to difficulty
breathing and swallowing.
• Patients with MG cannot sustain or repeat muscle contractions
B. Electromyography (EMG) studies
• When a motor nerve is stimulated (3 Hz), decrement of
response of at least 10% by the fifth stimulus.
C. Antibodies to acetylcholine receptors:
• May be detectable; in equivocal cases
• However, antibody titers do not correlate with severity of
 Diagnosis of Myasthenia Gravis

D. Pharmacological test
• EDROphonium (Tensilon = acetylcholinesterase inhibitor) test may help
to differentiate MG when responses to EMG studies are equivocal.
• In patients with MG, an IV dose (2 to 10 mg) of the edrophonium may
elicit improvement in strength because it inhibits the degradation of
Acyl.
• In normal patients, no improvement in strength is seen.
E. Regional Curare test
• May be employed, if testing is still equivocal.
• In this test, an arterial tourniquet is applied to isolate the limb
and limit the drug’s systemic action.
• EMG is performed before and after administration of very small
doses of curare (0.2 mg) into a forearm.
• Patients with MG show a marked decrease in response to
GRADE NAME DESCRIPTION TESTING &
PROGNOSIS
1 OCULAR Involvement of ocular Electrophysiologic
muscles only, ptosis and testing of other
diplopia muscles = -ve
1A OCULAR + PERIPHERAL Involvement of ocular Electrophysiologic
muscles, no symptoms of testing of other
peripheral muscles muscles = +ve
2A MILD GENERALIZED Involvement of skeletal or Good response to
bulbar muscle drug therapy
No respiratory involvement
2B MODERATE More severe inv. of skeletal Fair response to
GENERALIZED or bulbar muscle drug therapy
DYS- phagia, arthria, diff
chewing w/o respiratory
involvement

3 ACUTE FLUMINATING Rapid onset of severe B + S Poor response to

4 LATE SEVERE
WEAKNESS + RESPIRTORY drug therapy
Low mortality rate
Severe MG developing >2 Poor response to
years after onset of sym. drug therapy
Poor prognosis

Clinical Classification of MG:

 Treatment Alternatives for MG

The mainstay of treatment for MG is to :

• Increase the amount of acetylcholine available at the
neuromuscular junction
• Increasing the likelihood of agonist-receptor interaction and
successful neuromuscular transmission.
1. Acetylcholinesterase inhibitors:
Neostigmine (Prostigmin), edrophonium,pyridostigmine (Mestinon)
• Physostigmine is not used because it crosses the BBB producing
central nervous system symptoms.
• Pyridostigmine has the best treatment
• Dosage requirements may need to be titrated:
 Over-dosage can cause cholinergic crisis
 Under-dosage can cause myasthenic crisis
 Treatment Alternatives for MG

2. Immuno-modulation Treatment:
• This may decrease the amount of circulating antibodies.
• In short-term, we give steroids
• In long-term therapy we give azathioprine, rituximab cyclophosphamide, cyclosporine,
methotrexate.
• Steroids can provide
• Clinical improvement in 80%
• Exacerbates symptoms because of direct inhibitory effects on neuromuscular transmission.
• Side effects due to prolonged therapy to such as osteoporosis, hypertension, and peptic ulcers.

3. Plasmapheresis or plasma exchange:

• This produces transient but dramatic improvement in clinical symptoms.
• Improvement may last days to weeks after the procedure. This treatment is
reserved for severe MG.
• Plasmapheresis can decrease levels of plasma cholinesterase, resulting in prolonged
effects of succinylcholine, that are metabolized by this enzyme.
4. Thymectomy:
• It provides significant long-term immunomodulation and improvement
• Many patients with MG have abnormalities of the thymus gland.
• Imaging (CT or MRI) may help confirm the presence of an abnormal thymus
• It is considered the treatment of choice
 Why MG patients are resistant to succinylcholine but sensitive to NDMR?
• Acetylcholine receptors are each activated by two acetylcholine
molecules, which causes a small electrical current across the membrane
at the motor end plate. When the summation of small currents from
multiple receptors reaches a threshold, the end plate depolarizes and
muscle contraction occurs.
• Patients with MG can have 80% fewer receptors
• Any factor that even minimally interferes with neuromuscular
transmission may cause severe weakness.
• Small amounts of NMDR may block enough receptors to interfere with
this transmission.
• Succinylcholine acts as an agonist at acetylcholine receptors and causes
neuromuscular blockade by
1. Depolarizing the motor end plate and
2. Preventing rapid repolarization.
• Because of the smaller number of receptors available in patients with
MG, larger doses of succinylcholine are required to activate sufficient
 How is a patient with myasthenia gravis optimized for surgery?

1) Patients should be admitted in remission when possible. Patients

with a history of respiratory disease or bulbar involvement benefit
from pulmonary function testing.
2) These patients should be informed of the potential for
postoperative intubation and ventilation
3) Educated in the use of incentive spirometers.
4) Premedication is best used with caution and avoided in patients
with respiratory difficulty
5) Steroids should be continued in the perioperative period
6) Preoperative anticholinesterases are controversial.
Withholding anticholinesterases may be challenging in patients who
are physically or psychologically dependent on them,
Anticholinesterase dosage may be reduced during the relative
immobility for surgery.
 Anesthetic technique with cervical thymectomy:
1) Balanced anesthesia and total intravenous anesthesia ( TIVA )
2) TIVA with thoracic epidural anesthesia to reduce the need for
neuromuscular blocking agents and systemic opioids.
3) Standard monitors in place. When muscle relaxants are to be
administered, peripheral nerve stimulation is used.
4) De-nitrogenation with 100% oxygen,
5) Induction of anesthesia is achieved with propofol, etomidate, or
ketamine
6) In elective cases, relaxation for tracheal intubation is readily
achieved with a potent inhaled anesthetic agent.
7) In balanced techniques with small incremental doses of
intermediate-acting non-depolarizing muscle relaxants. It should be
titrated at one tenth the usual dose.
 Considerations for rapid-sequence induction with MG
1) Patients with MG are at increased risk for aspiration.
2) 1.5-mg/kg dose of succinylcholine has been successfully used to
facilitate intubation in a rapid-sequence fashion in patients with MG.
3) Patients with MG frequently do not show fasciculation with
succinylcholine.
4) Sugammadex is a cyclodextrin drug that is designed to bind
rocuronium with great affinity, providing rapid and effective
antagonism of deep rocuronium-induced neuromuscular (within
210s) in patients with MG.
5) Lidocaine, propofol, and remifentanil has been described. This
technique allows for a case to be managed without the potential
adverse effects of neuromuscular blocking agents. But intubating
conditions are frequently poor when neuromuscular blocking agents
are omitted.
 After emergence from anesthesia and before
extubation, how is adequacy of strength assessed?
1. In normal patients, when 50% of receptors are occupied a negative
inspiratory force of 220 cm H2O may be observed. When 33% of receptors
are occupied - patients can sustain a head lift for 5 seconds.
In normal patients, other measures of strength:
1 - Maintaining a tidal volume of 6 mL/kg
2 - TOF fade ratio greater than 0.9
3 - vital capacity of 15 mL/kg.
2. Patients with MG the disease, rather than residual neuromuscular
blockade, may prevent a patient with MG from reaching full strength. So,
preoperative measurements of strength are important for postoperative
comparisons. Control EMG or TOF should be recorded.
• It is important that a patient with MG have good muscle function so as to be
able to cough and clear secretions.
• Patients with MG who demonstrate residual weakness on emergence from
anesthesia should not automatically be assumed to have residual blockade
from a muscle relaxant.
• Interference with neuromuscular transmission by inhaled anesthetics,
antibiotics, local anesthetics, anticonvulsants, and b-adrenergic blockers may
What is a cholinergic crisis, & how is it distinguished from a myasthenic crisis?

Cholinergic crisis is the acute onset of muscle weakness in a

patient with MG.

It arises from an excess of acetylcholine at nicotinic and

muscarinic receptor sites due to excess anticholinesterase
administration.

Symptoms include weakness, wheezing, increased

secretions, bradycardia, and hypotension.
Respiratory weakness may progress to respiratory failure,
whereas increased secretions and dysphagia predispose to
upper airway obstruction and aspiration pneumonitis.
Two means of differentiating between
Both cholinergic crisis and myasthenic crisis are
1- to check pupillary size
A patient in a cholinergic crisis has constricted
pupils (miosis), whereas a patient in myasthenic
crisis has dilated pupils (mydriasis).

2- a small dose of intravenous edrophonium (2 to 10

mg)
• improves strength in a patient in myasthenic crisis
• no change or an exacerbation in cholinergic crisis
 Preoperatively predicted postoperative ventilation

A) positive predictors
1- duration of MG greater than 6 years,
2- History of chronic respiratory disease
3- pyridostigmine dose greater than 750 mg/day,
4- preoperative vital capacity less than 2.9 L.
5- thymectomy by transsternal more than transcervical
For high-risk patients,
• Preoperative plasma exchange
• High-dose perioperative steroid therapy,
can help reduce the probability of respiratory failure.