Week 2 - Neuromuscular Disorder Anesthesia Flashcards
Describe the steps of neuromuscular junction activity
- Action potential spreads over terminal – voltage gated Ca channels open – allows for large quantities of Ca to diffuse to the inner terminal
- Synaptic vesicle fusion - Ca causes fusion of synaptic vesicles with membrane of axon terminal
- Release of ACh – ACh is contained within vesicles is released by exocytosis into synaptic cleft – Ca ions are pumped out of axon terminal
- ACh binds to specific receptor – ACh gated ion channels, channels closed until ACh binds to 2 alpha sub units – undergo conformational change and channel opens (K+ out, Na+ and Ca+ in) – electrical potential at motor end place initiates AP (propagates along sarcolemma down T tubules and myofibrils) – muscle contraction
How is ACh broken down?
Rapidly broken down by acetylcholinesterase into Choline which is recycled to ACh and Acetate
Small amount diffuses out of synaptic space
*causes termination of the action potential
What is multiple sclerosis?
Autoimmune disorder that affects brain and spinal cord (CNS)
Damage to myelin sheath – nerve signals are disrupted and slowed or stopped = dysfunction
Caused by inflammation – generally unknown etiology
What does normal nerve conduction along myelinated fibers look like?
Nodes of Ranvier occur every 1-3 mm along myelin sheath – action potentials occur here = “Saltation”
Myelin membrane provides insulation for the nerve fiber
- decreases capacitance which increases electrical resistance (prevents current from leaving the axon)
- allows repolarization with minimal energy lost
- allow conduction at high rate of velocity
What are the signs and symptoms of multiple sclerosis?
- Vary based on location
- Often described as “attacks” (can last for days, weeks, months)
- Associated with periods of remission (reduced or no symptoms)
- Overall general deterioration over time – inability of body to re-myelinate
Environmental influence: fever, sun exposure, heat and stress can trigger or even worsen “attacks”
How is multiple sclerosis diagnosed?
Thorough neuro exam
MRI and nerve function tests (evoked potentials)
LP also common – looks at immunoglobulins and presences of albumin in CSH
What is the treatment for multiple sclerosis?
No Known Cure!
Goal is to control symptoms
- Steroids
- Interferons
- Methotrexate
- Fingolimod
- IV Ig
- Antidepressants
- Dantrolene
- Amantadine for fatigue
What are the preop considerations for MS?
- Thorough H&P
- Detailed neurological exam and discussion of symptoms/attacks
- Document any preop neurologic deficits
- Preop Labs - steroids (adrenal insufficiency?), Dantrolene (liver dysfunction)
- Stress increases MS symptoms –> Diazepam
What are the intraop considerations for a patient with MS?
GETA preferred:
- Propofol is induction agent of choice
- Volatile agents are safe
- Neuromuscular agents should be used with caution (variable response to NDMRs, Avoid SUX - hyperkalemia) – increased risk of residual weakness and resp distress
- Higher increase of invasive monitoring (autonomic dysfunction, monitor temp very carefully)
What are neuraxial anesthesia considerations in a patient with MS?
- Relative contraindication to spinal – exacerbation of symptoms, nerve root exposed to higher concentration of drug causing local neurotoxicity
- Epidural is ok — combination of local and opioid, reduced doses of meds required (keep infusion duration as short as possible), actually beneficial in MS pts in labor
What are postop considerations for a patient with MS?
Monitor closely due to risk of decline
- more often associated to fever than particular anesthetic
- respiratory weakness – higher FiO2 need and PPV?
What is Myasthenia Gravis?
Autoimmune Disease
- Weakness of voluntary skeletal muscles – most often muscles innervated by cranial nerves (any muscle can be affected)
- Caused by antibodies of nicotinic ACh receptors (reduced receptors, increased destruction of receptors)
- Incidence is 20 per 100,000
What are signs and symptoms of Myasthenia Gravis?
- Weakness with exertion (classic sign)
- Muscle groups commonly affected = eye, mouth, throat, and limbs
- often lead to resp muscle weakness and risk of aspiration
- Hyperplasia of Thymus
What are the Osserman and Genkins Classifications of Myasthenia Gravis?
I - Ocular only (Ptosis and diplopia)
IIA - Generalized moderate weakness and/or bulbar dysfunction
III - Acute fulminent presentation and/or resp dysfunction
IV - Late severe generalized
What are the main goals of treatment for Myasthenia Gravis?
- Increase neuromuscular transmission – use cholinesterase inhibitors (Edrophonium)
- Decreasing circulating antibodies – plasmapheresis, 4-8 plasma exchanges over 1-2 weeks
- Immunosuppressive therapy (Corticosteroids or Asathioprine)
What are preop considerations for Myasthenia Gravis?
- Respiratory status – low vital capacity, Thymoma?, assess for resp infection
- Cardiac status – cardiac arrhythmias (A-Fib, Sinus Brady, PVC’s, ST and T wave changes
- History of Rheumatoid?? – C-spine films within 2 years
What are the GETA intraop considerations for a patient with Myasthenia Gravis?
- Induction with Propofol, Thiopental, Etomidate
- TIVA vs Inhalational (inhalational agents have neuromuscular blocking effects)
- NDMR (avoid if possible) – utilize effects of volatiles, reduced number of ACh receptors, sensitive to nondepolarizers
- SUX (MG pts are more resistant to SUX, use with caution)
What are the regional anesthesia intraop considerations for a patient with Myasthenia Gravis?
Regional anesthesia is preferred
- Ester locals should be reduced or avoided in pts receiving anticholinesterase drugs
- Regional for labor and delivery – symptom exacerbation common during pregnancy (second term labor increases due to skeletal muscle weakness)
What are postop considerations for a patient with Myasthenia Gravis?
- Post op mechanical ventilation common due to residual weakness
- Pain is often not adequately controlled – sensitivity to respiratory side effects of opioids
- use of regional anesthesia for post op pain
What is a Cholinergic Crisis?
Excessive ACh at neuromuscular junction
-due to inactivity or inhibition of acetylcholinesterase (via nerve gas, overdose on cholinergic agents, surgical pts)
Signs and Symptoms: increased weakness and muscarinic effects (bradycardia, excess salivation, bronchoconstriction)
How do you determine if it is a Myasthenic Crisis or Cholinergic Crisis?
Give Edrophonium (anticholinesterase) – 1-10mg
If pt improves = Myasthenic Crisis
If pt condition worsens = Cholinergic crisis
What is Eaton -Lambert Syndrome?
Faulty communication between nerves and muscles
- Pre junctional alteration (decreased release of ACh)
- Often associated with malignancy (Oat Cell Lung Cancer)
- Affects peripheral and pelvic muscles
- May improve with exercise (unlike MG, ACh can build up for strength to improve somewhat)
- No improvement with anticholinesterases
- Sensitive to NMBD - use with caution
What is Duchenne disease?
Muscular Dystrophy – X linked recessive condition
- most common severe childhood myopathy
- occurs 1:3300 male births
- pelvic weakness between age 2-6 followed by proximal muscle atrophy and delayed motor milestones – Gowers Sign
- teenage years – immobility –> spinal muscle deformity (Scoliosis) –> respiratory failure due to intercostal muscle involvement –> cardiomyopathy also common
What are preop considerations in a patient with Duchenne?
Evaluation is critical!
Detailed cardiac and respiratory exam
Obesity – thick hypertrophic tongue very common
Difficulty with intubation/ventilation due to scoliosis?
What are intra op considerations for Duchenne?
- Airway management (be prepared) – awake fiberoptic intubation?
- Potential for aspiration (Na Citrate, Pepcid, Reglan?)
- ECG changes typical – cardiomyopathy – tall R wave in lead V1, deep Q wave in lateral leads, sinus tachy and shortened PR interval common
- Positioning problems – kyphoscoliosis/contractures of limbs
Malignant Hyperthermia is associated with which neuromuscular disorder?
Duchenne
- avoid MH triggering agents (inhalational agents/SUX)
- TIVA
**increased risk of MH in ALS as well
What is the concern with muscle relaxant usage in Duchenne?
Lead to postop respiratory weakness
Many case reports of cardiac arrest
-hyperkalemia from SUX, periop Rhabdo
What is Guillan Barre Syndrome?
Autoimmune disorder characterized by acute inflammatory demyelinating disorder
- can occur at any age, but more common between ages 30-50
- number one cause of acute muscular weakness
- generally preceded by infection (lung or GI) – usually minor infection
What are signs and symptoms of Guillan Barre Syndrome?
– Ascending symmetrical motor weakness (loss of reflexes in arms / legs) – Numbness/ tingling in legs/ arms – Tenderness or muscle pain – Blurred vision / double vision – Palpitations / difficulty breathing
*symptoms usually plateau within 28 days
How do you diagnose Guillan Barre Syndrome?
Nerve conduction studies, EMG, PFT’s, ECG, CSF
*diagnosis by exclusion
What is the treatment for Guillan Barre Syndrome?
Supportive
- Plasmapheresis effective (takes multiple exchanges)
- IV IG frequently part of treatment plan (may be more useful than Plasmapheresis, Pain should be treated with NSAIDs)
- Respiratory failure may occur if intercostal muscles affected (intubation and get them through until symptoms resolve with treatment)
*Complete recovery usually within weeks
What are the anesthetic considerations for Guillan Barre Syndrome?
Sensitivity to muscle relaxants
Avoid SUX due to risk of hyperkalemia due to extrajunctional receptors
May have hemodynamic variability (low BP) during acute phase
What is Amyotrophic Lateral Sclerosis?
Progressive loss of upper and lower motor neurons and effects medulla
- causes severe muscle weakness, disability, and ultimately death
- starts with twitching of peripheral extremity – difficulty swallowing, slurred speech
- progresses to affecting autonomic functions – breathing, BP, HR
approx 95% of case etiology is unknown
What are the anesthetic considerations for a patient with ALS?
- Spasticity of limbs (positioning problems)
- Severe muscle weakness/ atrophy/ weight loss (deconditioning, respiratory failure, dysphagia)
- Increased risk of MH – take precautions
- No SUX (up regulation of ACh receptors) – causes hyperkalemia, prolonged response to NDMRs
- Hypothermia – loss of autonomic function
What is Parkinson’s Disease?
Degenerative disease of CNS
-loss of dopamine producing cells in Substantia Nigra
Symptoms (Extrapyramidal):
- movement related – shaking, rigidity, slowness of movement, impaired walking/gait
- later signs include behavioral and cognitive delays (dementia)
What are the treatment options for Parkinson’s Disease?
Focus on managing symptoms
- Levodopa and Dopamine agonists
- COMT inhibitors, MAO B inhibitors, anticholinergics, Amantadine
- over time drugs become ineffective at treating symptoms and can cause dyskinesias
- Diet and rehabilitation are effective for some time
What is the surgical intervention to treat Parkinson’s?
Deep Brain Stimulation
- reduce motor symptoms in severe cases where drugs are ineffective
- surgeons implant electrodes into brain – connect to generator in chest that sends electrical impulses to brain
- not curative
- can provide significant relief of symptoms
What are the anesthetic considerations for a patient with Parkinson’s Disease?
- Be aware of autonomic dysfunction – orthostatic HoTN, constipation, incontinence, excessive sweating
- Respiratory dysfunction due to uncoordinated voluntary movements (rigidity and muscle weakness may be present)
- GI stasis and increased risk for aspiration
- Psych symptoms including delusions and hallucinations
- Potential for drug interactions (Levodopa causes severe N/V – MAO inhibitors contraindicated in pts taking Levodopa)
- Avoid Phenothiazine, Butyrophenone, and Reglan
What type of anesthetic should you do for a patient with Parkinson’s Disease?
Regional and General OK
– Regional allows for communication w/ patient
– Avoid muscle relaxation and potential side effects
– Increased incidence of PONV w/ GA in Parkinson’s patients
– Improved pain relief and potentially decreased stress response w/ regional anesthesia
– Increased risk of pneumonia or URI in PD patients w/ GETA
– Regional and sedation do not eliminate PD symptoms – Tremor or rigidity may compromise surgeons work environment, Delicate surgery (Patient may not be able to be completely still without GETA), Surgical procedure may not be possible under regional
What is Malignant Hyperthermia and its triggers?
Life threatening disorder of skeletal muscle
Triggers = succinylcholine and inhalational anesthetics
*uncommon and inherited in some families – autosomal dominant pattern
What is the pathophysiology of malignant hyperthermia?
50-70% - mutation of Ryanodine receptor (type I)
- defect in Sarcoplasmic reticulum of skeletal muscle
- affects calcium regulation
Multiple other mutation possibilities – end result is greatly increased Calcium release (causes consumption of large amounts of ATP causing excessive heat and damage to muscle cell)
What are the signs and symptoms of malignant hyperthermia?
- Extremely high temp
- Tachycardia
- Increased CO2 production and O2 consumption
- Acidosis
- Muscle rigidity and rhabdomyolysis
*usually develop about 1 hour after exposure, but can occur later
What lab findings will you see with malignant hyperthermia?
PCO2 >60 Base excess more negative than -8 pH <7.25 K+ > 6 CK > 10,000 even without use of SUX Myoglobin >170mcg Urine Myoglobin >60mcg
What are the preop considerations for malignant hyperthermia?
- Family history of life threatening problem with anesthesia – High fever, unexpected death, etc
- Family or personal history of cola colored urine after anesthetic
- Linkage to Duchenne and other dystrophy’s
Absence of positive pt or family history doesn’t preclude the pt from having MH
How do you treat malignant hyperthermia?
- Get Help – tell surgeon what is going on – need to end the case NOW
- Stop volatile agent
- 100% O2 and hyperventilate
- Dantrolene 2.5 to 10 mg/kg (each vial contains 20mg and mix in 60cc sterile water
- Treat arrhythmias, acidosis, electrolyte abnormalities (avoid Ca channel blockers)
What are the anesthetic considerations for intraop management of suspected malignant hyperthermia?
- Standard ASA monitors
- Prepare machine – MH specific machine? Changed bellows, tubing, etc.. Flush with 100% O2 for 30 min, tape over volatile agent slot
- Absolutely avoid volatile agents and SUX (TIVA, local, regional all ok)
- MH cart available outside pharmacy! (26 vials of Dantrolene in cart)
What diagnostic testing is used to diagnose malignant hyperthermia?
Caffeine Halothane Test – Gold standard
- thigh muscle biopsy - measure contractility response to caffeine, halothane, or both
- *Negative biopsies are not definitive**
Genetic testing – performed on a limited basis (usually strong family hx)
