Transcript Disorders of Muscle and Neuromuscular Transmission

Neuromuscular Disorders:
disorders of neuromuscular junction,
motor neuron, and muscle
Kasia Petelenz
Greg Gordon (and others)
November 15, 2005
Myasthenia Gravis
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Incidence 1:10,000 to 1:30,000
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Women 20 – 30 years of age are most often
affected; men older than 60 display symptoms
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Acquired chronic autoimmune disorder
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Hallmarks are weakness and rapid exhaustion
of voluntary skeletal muscles
Myasthenia Gravis
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Muscle strength characteristically improves
with rest, deteriorates rapidly with exertion
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Skeletal muscle atrophy is unlikely
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Laryngeal and pharyngeal muscle weakness
may lead to aspiration, problems clearing
secretions, difficulty chewing.
Myasthenia Gravis Presentations
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Clinical Classification
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Class 1: ocular symptoms only
Class 1A: ocular symptoms with EMG evidence of
peripheral muscle involvement
Class 2A: mild generalized symptoms
Class 2B: more severe and rapidly progressive symptoms
Class 3: acute and presenting in weeks to months with
severe bulbar symptoms
Class 4: late in the course of disease with severe bulbar
symptoms and marked generalized weakness
Myasthenia Gravis
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Disease course marked by exacerbations and
remissions
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Infection, stress, surgery, pregnancy have unpredictable
effects, but often cause exacerbations
Antibiotics can aggravate weakness
Diseases considered AI in origin often coexist
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Decreased thyroid function
RA
SLE
Pernicious Anemia
Mechanism - MG
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Decrease in functional Acetylcholine
receptors at the nicotinic neuromuscular
junction
70% - 90% have circulating antibodies to
AChR’s
Neonatal
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Transient born to mothers with MG – Ab’s cross placenta
Only 12% symptomatic
Therapy - Myasthenia Gravis
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Immunosuppressants:
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Plasmapheresis, iv immunoglobulin
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Steroids - Commonly cause dose dependent weakness
Azathioprine,Cyclosporine
Acute exacerbations, i.e. in immediate post-operative
period if anticholinesterases have been withheld and
symptoms are severe
Plasmapheresis + IVIG for 5 days -> rapid improvement,
may last for weeks
Thymectomy
Important part of Rx
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Anticholinesterase drugs
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Pyridostigmine, po duration of 2-4 hours
Excessive administration -> Cholinergic Crisis
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SLUDGE: Salivation, lacrimation, urination,
defecation, + miosis + bradycardia + bronchospasm
Profound weakness: due to excess Ach at NMJ ->
persistent depolarization
Treatment of Cholinergic Crisis: Atropine,
Mechanical Ventilation if needed
Anesthetic Concerns - MG
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Pre-op Predictors of Need for Post-Operative
Ventilatory Support
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Disease duration > 6 years
Concomitant pulmonary disease
Maximum inspiratory force (MIF) <-25cm H2O
VC < 4 mL/kg
Pyridostigmine dose >750 mg/day
Anesthetic Considerations
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Old School: Recommended to d/c anticholinesterase
if pt has only mild weakness
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Theory: Potentiates Sux, inhibit effect of NDMR’s
Pts more susceptible to vagal arrhythmias
Slows metabolism of ester LA’s, Sux, Mivacron
New School: No experimental evidence to suggest
that altering a pt’s anticholinesterase regimen has
any clinically significant effect on NMB or duration
of mechanical ventilation post-op.
Anesthetic Considerations
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Increased risk for aspiration
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Premed with Reglan/Ranitidine
Reduced respiratory reserve
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Avoid premeds with opioids, benzo’s
Pts are very sensitive to respiratory depressant
effects
Anesthetic Considerations - MG
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Response to Sux is unpredictable
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Relative resistance usually seen
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Exquisitely sensitive to NDMRs!!
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ED95 approximately 2.6 x normal
All NDMRs have been used successfully and uneventfully
if twitches are monitored
Should be titrated in 1/10 to 1/20 normal dose
Sensitivity to NMDRs is increased during coadministration of potent inhaled anesthetic
Reverse with standard doses of anticholinesterase
and anti-cholinergic
Post-Op Considerations – MG
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Case Scenario: Pt extubated in OR, 40 minutes later
c/o feeling weak and unable to breathe
Myasthenic crisis: decreased response to
anticholinesterases
Cholinergic crisis: overdose of anticholinesterases
Both: increases in muscle weakness, salivation, and
sweat occur
Post-Op Anesthetic Considerations –
Myasthenia Gravis
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Differentiate with response to 10mg iv
Edrophonium:
Myasthenic crisis shows some improvement
in muscle strength
Cholinergic crisis shows no increase in
muscle strength and worsening of respiratory
distress.
MG upstairs
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Epidural Analgesia preferred
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No evidence that MG pts are more sensitive to LA
used for conduction anesthesia, but MG predisposes
to increased weakness
Amide LAs probably better:
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Maintains SV and LA dose can be easily titrated
Hepatic Metabolism
Not hydrolyzed by serum cholinesterases
Emergent C/S
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Sux to allow rapid control and protection of airway
Lambert-Eaton Syndrome
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Mimics Myasthenia Gravis
Most often affects older males
Usually associated with Small Cell CA (lung)
Voltage increment to repeated stimulation and a poor
response to anticholinesterases
Sensitive to NMDR’s, normal/increased response to
Sux
Antibodies to Ca channel associated protein
synaptogamin present
Motor Neuron Diseases
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Degeneration of upper
and/or lower motor
neurons
i.e. Amyotrophic Lateral
Sclerosis
Muscular weakness and
atrophy
Steady, asymmetric
progression
Sensory systems, voluntary
eye movements, and
urinary sphincters are
spared
Amyotrophic Lateral Sclerosis
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Progressive neuromuscular disorder
Characterized by degeneration of spinal motor
neurons, leading to:
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Denervation
Muscle wasting
Paralysis
Eventually death, most often secondary to
respiratory failure
ALS – Anesthetic Concerns
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Increased Sensitivity to NDMRs
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Reduction in choline acetyltransferase (involved
in synthesis of ACh) occurs secondary to
degeneration of anterior horn cells
Avoid Sux
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Hyperkalemic response in degenerating muscles
ALS – Anesthetic Concerns
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GA documented to cause ventilatory
depression post-operatively, even without use
of muscle relaxants
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Respiratory complications are common and a
major cause for concern
Regional relatively contraindicated in pts with
motor neuron disease, including ALS, for the
fear of exacerbating the disease
ALS – Case Description
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76 y/o with rapidly progressing ALS, s/p
femoral head fx
PE: siallorrhea, dysarthria, dysphonia,
cachexia
Recent PFT’s reveal 20% nL lung function
Refused to withdraw “Do not intubate” orders
for the intra and post-op time frames
Intra-Op Course
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Intrathecal Catheter placed at L3/4
0.25 mL of Bupivicaine 0.75% (1.9 mg) injected
through catheter
T8 level
Catheter was discontinued upon completion of case
POD #1: minor desats, resolved with O2 therapy
No c/o HA during post-op course
Choice of most minimally invasive
anesthetic method
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Case reports have documented successful use
of epidural anesthesia
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Gradual onset of block
Less hemodynamic instability
But inadequate epidural anesthesia may result
Incremental Intrathecal technique allowed
adequate anesthesia without adverse
hemodynamic consequences, and enabled
extension of block as needed
Disorders of Muscle
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Congenital Muscular
Dystrophies
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Myotonic
Duchenne, Becker
Acquired Myopathies
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Cushing’s Syndrome
Dermatomyositis
Polymyositis
Myotonic Dystrophy
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Characterized by persistent contractures of skeletal muscles
after voluntary contraction or following electrical stimulation
Peripheral nerves and NMJ are not affected.
Abnormality in the intracellular ATP system that fails to
return calcium to the sarcoplasmic reticulum
Contractures are not relieved by NDMRs, regional or deep
anesthesia
Infiltration of LA into skeletal muscle may induce relaxation
Depression of rapid sodium flux into muscle cells by
phenytoin, procainamide, quinidine, may alleviate contracture
by delaying membrane excitability
Characteristic Appearance - MD
Coexisting Organ Dysfunction - MD
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Cardiac Involvement
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Mitral valve prolapse – 20% of individuals
Deterioration of the His-Purkinje system lead to
arrhythmias
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1st degree AV block very common
Pulmonary Pathology
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Restrictive lung disease
Impaired responses to hypoxia and hypercarbia
Coexisting Organ Dysfunction - MD
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Cataracts very common
GI abnormalities
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Gastric atony
Intestinal hypermotility
Pharyngeal muscle
weakness with impaired
airway protection
Cholelithiasis
Anesthetic Pre-Op Concerns
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Eventually develop extremely compromised
respiratory function
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Pulmonary Aspiration, Pneumonia
Chronic Alveolar hypoventilation because of
impaired neuromuscular function -> chronic
hypercapnea
Decreased FRC, VC, MIP
Avoid premeds – very sensitive to respiratory
depressant effects of narcotics and benzos
Anesthetic Concerns MD
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Avoid Etomidate
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Avoid Sux
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May cause myoclonus and precipitate contractures
Produces an exaggerated contracture
Susceptible to MH
Avoid Anticholinesterases – may precipitate
contracture by increasing ACh available at NMJ
Keep room warm – shivering may lead to
contractures
Anesthetic Concerns MD
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Exaggerated effects of myocardial depression from
inhaled agents- even Asymptomatic pts have some
degree of cardiomyopathy
Anesthesia and surgery could theoretically aggravate
co-existing cardiac conduction blockade by
increasing vagal tone or causing transient hypoxia of
the conduction system
Pregnancy:
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Exacerbation of symptoms is likely
Uterine atony and retained placental often complicate
vaginal delivery
Guillaume Benjamin Amand Duchenne
The French
neurologist, who
studied and defined
many
neuromuscular
diseases, in the mid
1900’s, including
the one named for
him
Completely irrelevant side note
Duchenne investigated facial expression in a
crude but effective manner of ‘shocking’ the
facial muscles using galvanic current –
defined “facial expressions”
Duchenne Muscular Dystrophy
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Most common muscular dystrophy encountered by
anesthesiology
Incidence 1:3,500 live male births
Characterized by painless degeneration and atrophy
of skeletal muscles
X-linked disorder
 DMD gene isolated to short arm of the X
chromosome at position 21
 Estimated mutation rate is one of the highest for
any human disease
Duchenne Muscular Dystrophy
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DMD gene product:
dystrophin
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Associated with muscle
cell membranes
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Absent or nonfunctional in
DMD patients
In its absence, a sequence of
events occurs that leads to
calcium influx into the
muscle cells -> cell
degeneration and death
Affects Skeletal, Cardiac,
and Smooth muscle
Progressive disease course
DMD: Disease Progression
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Under 2 yrs old
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2-5 yrs old
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Behave like healthy toddlers
First outward signs of muscular weakness
Clumsiness, frequent falling, waddling gait, difficulty
climbing stairs
Calf muscles begin to look enlarged
6-12 yrs old
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Child walks on toes secondary to Achilles tendon
tightening and to compensate for weak quads
Weakening pelvic and shoulder girdles -> compensatory
lordosis
Gowers’ Maneuver
DMD: Disease Progression
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8-14 yrs old
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Adult phase
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Lose ability to walk
Decrease in caloric requirements -> even normal diet
leads to obesity
95% develop scoliosis
Scoliosis + weakened respiratory muscles, inactivity,
obesity -> compromised lung expansion and function
Vital capacity decreased approximately 50%
Weak cough -> vulnerable to pneumonia
Late 20’s
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90% die of respiratory complications, 10% cardiac
Cardiopulmonary Dysfunction
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Degeneration of cardiac muscle inevitable
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Tall R waves in V1; deep Q waves in limb leads; short PR
intervals; sinus tach
MR due to papillary muscle dysfunction
Decreased cardiac contractility
Pulmonary difficulties
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Chronic weakness predisposes to decreased ability to
cough, leads to accumulation of secretions -> pneumonia
Sleep apnea common -> pulmonary hypertension
Case Report: DMD, PEG, and LMA
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20 yr old with DMD
Chronic Respiratory Failure
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Vital Capacity 450 mL (9% predicted)
Maximum inspiratory and expiratory pressures: -20 and
+5 cm H2O
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Cough peak flow of 40 L/min
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To generate effective cough: MEP >60
Cough <160 L/min associated with ineffective airway clearance
On 24 hr nasal BiPAP, settings 20/7, rate 16
Case Report: DMD, PEG, and LMA
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CHF
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LVEF 20%
Physical Exam:
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hypertrophied tongue
MP III
muscle strength 1-2/5 upper and lower
extremities
Case Report: DMD, PEG, and LMA
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Procedure performed in PACU
Standard monitors
Premed: 1mg Midazolam, just prior to induction
Induction:
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300mcg/kg/min Propofol, adj for maintenance as
needed
30 mg Ketamine
SV with NPPV until eyelash reflex abolished
Case Report: DMD, PEG, and LMA
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Appropriate LMA inserted
Well lubricated gastroscope passed through the
mouth, behind LMA
LMA deflated as necessary to allow better scope
navigation
Ventilation assisted as needed to maintain PaCO2
35-40
LMA removed after procedure under deep sedation
with spontaneous ventilation, and NPPV replaced
PICU monitoring overnight, d/c home < 24 hours
Why this type of
anesthetic?
Anesthesia Concerns with DMD
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Lingular hypertrophy: difficult intubation
Association with MH has been suggested but
not validated
But, avoid volatile agents if possible, and
keep Dantrolene available
Anesthesia Concerns with DMD
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NDMR’s ok, but action is prolonged
SUX IS CONTRAINDICATED
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Regenerating muscle fibers, common in DMD until at
least 8 years of age, are considered to be more vulnerable
to the effects of SUX
Difficult Extubation:
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Endotracheal edema
Mucosal congestion
Inability to clear retained secretions
Acute respiratory failure
Review Questions (Hall)
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173. Which of the following diseases is
associated with increased resistance to
neuromuscular blockade?
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A. Myasthenia Gravis
B. Myasthenic Syndrome
C. Huntington’s chorea
D. Duchenne muscular dystrophy
Answer: A
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Myasthenia Gravis
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Myasthenic Syndrome (Eaton Lambert)
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Decreased release of Ach but normal number of AChRs
Sensitive to Sux and NMDRs
Huntington’s chorea
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Fewer AChRs.
Resistant to Sux.
Sensitive to NMDR’s.
Decreased plasma cholinesterase activity
Prolonged response to Sux
Duchenne Muscular Dystrophy
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Sux is relatively contraindicated
NMDR’s have a normal response, although patients have prominent skeletal
muscle weakness.
Review Questions (Hall)
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489. 37 y/o male with myasthenia gravis, to ED, confused,
agitated, 2 day h/o weakness, SOB. RR 30 breaths/min, TV
4mL/kg.
 ABG: PaO2 60; PaCO2 51; HCO3 -25;
pH 7.3;
SaO2 90%
 Edrophonium 5mg iv -> TV 2mL/kg
A. Tracheal Intubation and Mechanical Ventilation
B. Repeat Edrophonium
C. Neostigmine 1 mg IV
D. Emergency Trach
E. Atropine 0.4 mg IV
Answer: A
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Cholinergic crisis vs. myasthenic crisis
Cholinergic crisis worsens with
administration of anticholinesterase
Pt should be electively intubated until strength
returns.
Review Questions (Hall)
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669. A lumbar epidural is placed in a 24 y/o
G1P0 with myasthenia gravis. Select the true
statement regarding neonatal MG.
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A. The newborn is usually affected.
B. The newborn is affected by maternal IgM
C. The newborn may require anticholinesterase
therapy for up to 3 weeks
D. The newborn will need lifelong treatment
E. Only female newborns are affected
Answer: C
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IgG antibodies are directed against AChRs
IgG can cross placenta
Neonatal MG is characterized by muscle
weakness (hypotonia, respiratory difficulty)
Presents within the first 4 days of life (80%
within first 24 hours)
Anticholinesterase therapy may be required
until the maternal IgG is metabolized
References
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Bach JR, Ishikawa Y, Kim H. Prevention of Pulmonary Morbidity for
patients with Duchenne Muscular Dystrophy. Chest 1997;112:1024-28
Benumoff JL, ed. Anesthesia & Uncommon Diseases, 4th Ed.
Philadelphia: WB Saunders. 9, 373-4
Brimacombe J, Newell S, Bergin A, et al. The Laryngeal Mask for
Percuatneous Endoscopic Gastrostomy. Anesth Analg 2000;91:635-6
Dillon FX. Anesthesia issues in the perioperative management of
myasthenia gravis. Semin Neurol. 2004 Mar;24(1):83-94.
Faust RJ, ed. Anesthesiology Review, 3rd Ed. Philadelphia: Churchill
Livingstone. 490-494
Hara K, Sakura S, Saito Y, et al. Epidural Anesthesia and Pulmonary
Function in a Patient with Amyotrophic Lateral Sclerosis. Anesth Analg
1996;83:878-9
References
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Morris P. Duchenne Muscular Dystrophy: a challenge for the anaesthetist.
Paediatric Anaesthesia 1997;6:1-4
Moser B, Lirk P, Lechner M, et al. General anaesthesia in a patient with
motor neuron disease. Eur J Anesthes 2004;21:921-922
Otsuka N, Igarashi M, Shmiodate, et al. Anesthetic management of two
patients with amyotrophic lateral sclerosis. Masui. 2004 Nov;53(11):127981
Pope JF, BirnKrant DJ, et al. Noninvasive Ventilation during percuatneous
gastrostomy placement in Duchenne Muscular Dystrophy. Pediatr
Pulmonol 1997;23:468-471
Stoelting RK, Dierdor SF, ed. Anesthesia and Co-Existing Disease, 4th Ed.
Philadelphia: Churchill Livingstone. 217,517-519,522-528
Yao FS, ed. Anesthesiology: Problem-Oriented Patient Management, 5th
Ed. Philadelphia: Lippincott Williams & Wilkins.1019-1032