Exam 1 Plus Some Peds :/ Flashcards
Where are smooth muscle (involuntary) found?
within the walls of organs and structures such as:
-esophagus
-stomach
-intestines
-bronchi
-uterus
-urethra
-bladder
-blood vessels
-arrector pili in skin
Cardiac and skeletal muscles are ___________.
striated
Where do cardiac muscles connect?
at branching, irregular angles–> intercalated discs
What do cardiac and skeletal muscles contain?
sarcomeres and are packed into highly regular, repeating arrangements of bundles
How are skeletal muscles arranged?
in regular, parallel bundles
What is the difference between striated vs. smooth muscle contraction?
striated muscle contracts and relaxes in short, intense bursts, whereas smooth muscle sustains longer or even near permanent contractions
Cardiac muscle is ______ muscle but more akin in structure to skeletal muscle and only found in the heart.
involuntary
Neuromuscular junction contains:
- presynaptic motor neuron
- synaptic cleft (contains acetylcholinesterase (AChase)
- Highly folded postsynaptic muscle fiber
Nerve stimulation
-depolarization reaches nerve terminal and voltage-gated calcium channels open
-storage vesicles (presynaptic) releases Ach into the cleft
-Ach diffuses across the synaptic cleft and binds to the nicotinic cholinergic receptor (postsynaptic)
What 5 subunits do fetal receptors contain?
2 alpha
1 beta
1 delta
1 gamma
What 5 subunits do mature receptors contain?
2 alpha
1 beta
1 delta
1 epsilon
What does the influx of calcium cause?
-Ach vesicles fuse with the nerve plasma membrane and then expel their content into the synaptic cleft
The amount of Ach released is influenced by what?
the amount of calcium that enters the nerve terminal during stimulation
-increased calcium that enters the nerve terminal–>increased amount of Ach released
What causes upregulation?
When frequency of stimulation of NMJ decreases over days due to:
-severe burns
-immobilization
-infection
-sepsis
-prolonged use of NMBAs in ICU, CVAs
-number of immature nAChrs increases (upregulation) within 24-48 hours
The number of immature nAChRs will have increased sensitivity to ________.
Ach and Sch (massive release of potassium if Sch given in patient with burn 24 hours after)
The number of immature nAChRs will have decreased sensitivity to __________.
nondepolarizers
What is Multiple Sclerosis characterized by?
-inflammation
-demyelination
-immune dysfunction
-failure of cell repair in the CNS
Downregulation is caused by _________________.
chronic neostigmine use (too much Ach around) decreases sensitivity of receptors to Ach
Multiple Sclerosis is a demyelinating disease of _______ & __________.
brain & spinal cord
causing:
-muscle weakness
-cognitive dysfunction
-memory loss
-personality disorders
What is the pathophysiology of MS?
autoimmune disease characterized by T-cell mediated autoantibodies against myelin (converts T-cells into inflammatory cells)
-peripheral nerves not affected
MS is 8x higher in ____________.
females
Symptoms of MS
-Depends on sites of demyelination
Brainstem symptoms of MS
DAAAN
-diplopia
-ataxia
-autonomic dysfunction
-altered ventilation
-nystagmus
Spinal cord symptoms of MS
-weakness and paresthesia (Legs > arms)
Other symptoms of MS
-bowel retention and urinary incontinence
-central neuropathic pain
-trigeminal neuralgia
-spasticity
-tonic seizures
Pregnancy is associated with a __________ risk of MS exacerbations.
reduced
In MS patients, the postpartum period may have an ____________ risk of relapse.
increased
Symptoms of MS appear between what ages
20-40 years
Clinical criteria for diagnosis of MS
s/s of CNS white matter disease
-2 or more attacks separated by a month or more
-involvement of 2 or more noncontiguous anatomic areas
-elevated levels of IgG and albumin in the CSF is abnormal
-MRI: demyelinated plaques in the CNS
White matter symptoms of MS
-memory problems
-slow walking
-balance issues or frequent falls
-difficult performing two or more activities at once, such as walking and talking at the same time
-mood changes, such as depression
-urinary incontinence
Goal in the Tx of MS
modulate the immunologic and inflammatory responses that damage the CNS
Medication Tx of MS
Disease-modifying agents->interferon beta (SE=flu like symptoms, elevated liver enzymes and neutropenia)
Immunosuppressants (azathioprine)
Corticosteroids
IV immunoglobulins
Symptomatic treatments for spasticity, depression and neuropathic pain (gabapentin, baclofen, and SSRIs)
Assessment of a MS Patient**
- Last neurologist appointment
- last time they had exacerbation of the disease
- bulbar or respiratory symptoms (post op ventilation)
- What medications are they taking?
- Lhermitte sign: neck flexion induces an “electrical sensation”
- visual disturbances due to optic neuritis
- Unthoff sign: worsening symptoms by increased body temperature (Exercise, hot temps); more remission in colder environments
- depression
Perioperative risks of a MS patient
-exacerbation of symptoms with hyperthermia, stress, surgery, infection, emotional and physical trauma, postpartum
-versed in preop
-consider stress steroids
-spinal anesthesia may exacerbate symptoms due to potential neurotoxicity
-epidural and peripheral blocks ok because staying out of CNS
-Avoid SUXX due to occurrence of hyperkalemia
-NMDR careful use (avoid if you can)
-post op respiratory support
What is the cause of Alzheimer’s disease?
-amyloid-beta protein
-this protein begins a cascade of events ending with deposits of:
- amyloid plaques
-neurofibrillary tangles
-neuronal apoptosis
-these cause a loss of cholinergic activity and loss of glutamatergic neurons
What is alzheimer’s disease characterized by?
-loss of cognition
-poor decision-making
-language and gait issues
-seizures
-agitation
-psychosis
Tx of Alzheimer’s disease
acetylcholinesterase inhibitors and a NMDA inhibitor
Anesthesia considerations for Alzheimer’s disease?
- postoperative cognitive dysfuction, careful with sedative premeds (i.e. versed)
- use glycopyrrolate (will not cross BBB)
- patients already receiving cholinesterase inhibitors to increase Ach, may have prolonged Sux response because they will have massive amount of Ach in system
do not want to use scopolamine or atropine because they can cross BBB and decrease Ach levels in brain
What is Parkinson’s disease caused by?
-degenerative CNS disease caused by loss of dopaminergic cells in the basal ganglia (Lewy Bodies)
-diminished inhibition of the extrapyramidal motor system due to dopamine deficiency
S/s of Parkinson’s
-resting tremor
-cogwheel rigidity of the upper extremities
-bradykinesia
-shuffling gait
-stooped posture
-facial immobility (frozen face)
Treatment of Parkinsons
Levodopa (multiple other drugs available)
Deep Brain stimulatorys
Anesthesia considerations of Parkinson’s disease
-1/2 life of Levodopa is short, interruption of therapy for more than 6-12 hours can result in severe skeletal muscle rigidity and ventilation issues
-avoid dopamine antagonists (Reglan, Phenergan)
-dopamine antagonists-phenothiazines, droperidol and metoclopramide should be avoided
-increased risk of neuroleptic syndrome with dopamine agonists
-autonomic dysfunction, upper airway dysfunction, postoperative confusion and hallucinations
-problems with swallowing and secretions
-alfentanil and fentanyl may produce dystonic reactions when administered rapidly
Deep Brain Stimulator (DBS)
2 part surgery: stimulator and generator placement
-most effective in people who suffer severe tremors
-suffer wearing-off spells or medication induced dyskinesia (uncontrolled shakes)
-not thought to improve speech or swallowing issues or thinking problems
-doesnt slow down disease process
-if doing sedline or bis monitoring will pick up stimulation so readings may not be accurate
Motor neuron disorders
upper, lower or mixed neuron involvement of the cerebral cortex, brainstem and spinal cord
ALS (Lou Gehrig’s disease):mixed
Kennedy’s Disease (spinobulbar muscular atrophy)
Friedreich’s Ataxia: mixed
Spinal muscular atrophy: lower motor neurons
What is Amyotrophic Lateral Sclerosis (ALS)?
-selective and progressive motor neuronal death
-progressive degeneration of the upper and lower motor neurons causing:
1. amyotrophy (muscle wasting)
2. lateral sclerosis
autonomic dysfunction
What gender and age is more affected with ALS?
Males>females
-40-60 years onset
Diagnosis of ALS
EMG and neuro exam that demonstrates early spastic weakness of the upper and lower extremities, subcutaneous muscle fasciculations and bulbar involvement affecting pharyngeal function, speech and facial muscles
Treatment of ALS
non curative
-tx symptomatically
Anesthetic considerations for ALS
-bulbar involvement: aspiration risk and pulmonary complications (highest)
-increased sensitivity to respiratory depressant effects of sedatives and hypnotics (avoid opioids and benzos)
-sympathetic hyperactivity and autonomic failure
-avoid Sux (risk of hyperkalemia due to denervation and immobilization)
-nondepolarizers may be prolonged and pronounced
-regional OK
-use short-acting anesthetics
-prone to atelectasis
Hyperkalemia periodic paralysis
sodium channel defect causes prolonged depolarization and flaccid paralysis
K>5.5mEq/L during symptoms
-skeletal muscle weakness may be localized to tongue and eyelids
Skeletal muscle channelopathies (myotonias)
-hyperkalemic periodic paralysis
-hypokalemic periodic paralysis
-sodium channel myotonia
-thyrotoxic periodic paralysis
-myotonia congenita
-paramyotonia congenita
-andersen-tawil syndrome
Precipitating factors of Hyperkalemic periodic paralysis
-rest after excercise
-potassium infusions
-metabolic acidosis
-cold exposure (OR hypothermia)
Hypokalemic periodic paralysis
calcium or sodium channel defect
K level <3 mEq/L during symptoms
-chronic myopathy with aging (70+)
Precipitating factors of hypokalemic periodic paralysis
-high glucose meals
-strenuous exercise
-glucose-insulin infusions
-stress
-hypothermia
Anesthetic management of hypo/hyperkalemic paralysis
-preoperative electrolytes and abnormalities corrected before surgery
-keep normothermic
-careful with medications that cause changes in potassium (insulin, diuretics) that can cause weakness or paralysis
-avoid anectine
-constant monitoring for potassium-related dysrythmias
-may be sensitive to nondepolarizing muscle relaxants due to chronic myopathy
What is Guillain-Barre Syndrome (polyradiculoneuritis)
-autoimmune disorder characterized by:
-onset of ascending skeletal muscle weakness or paralysis of the legs usually due to viral or bacterial infection
-group of disorders known as the inflammatory neuropathies
-autonomic dysfunction with wide fluctuations in HR/BP
-physical stimulation can precipitate HTN, tachycardia and cardiac dysrhthmias
-respiratory muscle weakness
Treatment of GB
based on symptoms
plasma exchange
immunoglobulin
mechanical ventilation
Anesthetic considerations of Gullain Barre
-avoid rapid movement of patient (autonomics)
-aspiration (reglan, pepcid)
-maintain temperature
-airway respiratory failure
-maintain preload and afterload
-careful with PPV (may cause autonomic instability) can trigger ganglia along spinal cord by pressure to cause autonomic dysfunction
-muscle relaxants (avoid Sux), increased sensitivity to NMDR; do not want to cause K release from cells because they will be upregulated
What is Myasthenia gravis caused by?
a decrease in the number of functional postsynaptic, Ach receptors in the neuromuscular junction available for Ach binding
-abnormal thymus tissue frequently involved
What is the hallmark sign of MG?
fatigability which improves with rest
Who does MG affect most?
bimodal disease:
-young women 30-40 yo
-older men >50 yo
Pathophysiology of MG
- major antigen in MG is acetylcholine receptor on the muscle membrane
- some patients without AChR antibodies have autoantibodies against Muscle Specific Kinase (MuSK)
-protein that allows AchR clustering at the NMJ - less commonly there are low-density lipoprotein receptor-related protein 4 (LRP4) in MG patients without MuSK or AChR
-receptor for neural agrin that relays the signal to MuSK to initiate AChR clustering
-patient without detectable antibodies against any of these 3 antigens are referred to as seronegative
Clinical hallmark of MG
skeletal muscle weakness that is aggravated by repetitive muscle use and improves with rest
First notable sign of MG
-“weakness of extra-ocular muscles”
-diplopia (double vision) common presenting complaint (cranial nerves)
Other s/s of MG
-muscles of facial expression, muscles of talking, chewing and swallowing especially affected
-weakness of arms/legs, bulbar symptoms or weakness of muscles of respiration
-environmental, physical, and emotional factors can affect the disease (surgery, pregnancy)
-myocarditis in patients with thymomas-will usually see cardiac defects (decreased EF)
Diagnosis of MG
Clinical tests of fatigability:
1. maintaining upward gaze
2. holding out an affected limb
3. respiratory function test
Electrophysiologic (EMG or supramaximal stimulation of peripheral nerve at 2 Hz)
Pharmacologic (Edrophonium/Tensilon test)
immunologic (anti-Achr antibody titer)
-85% have anti-AChR antibodies
-5% have no detectable antibodies
-10% may have antibodies against MuSK or LRP4
75-90% of MG patients have:
-thymoma
-thymic hyperplasia
-thymic atrophy
higher incidence of heart disease
What is the most common anterior mediastinal mass occurring in adults?
thymus hyperplasia
Myasthenic crisis is characterized by:
-progression of severe muscle weakness
-respiratory failure
-bundle branch blocks and A-fib
MG and pregnancy
pregnancy exacerbates symptoms of MG in 33%
-some pregnant women experience remission or no change
Causes of myasthenic crisis
-poor control of MG, underdosing of meds
-emotional stress
-hyperthermia
-pulmonary infection (severe PNA or bronchitis)
Exacerbations of MG in pregnancy are most likely to occur during:
1st trimester
or
6 weeks post-partum
Anti-AchR antibodies cross the placenta
Magnesium should be avoided (for tocolysis and preeclampsia)?
The newborn of a mother with MG can suffer from _______________
transient neonatal myasthenia
Transient neonatal myasthenia may present with:
-difficulty feeding
-ptosis
-facial weakness
-respiratory distress at birth
Transient Neonatal myasthenia
-in newborns of women with active MG
-can begin 12-48 hours after birth and last for weeks
-spontaneous remission at 2-4 weeks when maternal antibodies clear circulation
-edrophonium testing (tension test): improvement in strength==positive result
-serologic testing
-tx of symptom management and immunomodulation
What conditions are associated with MG
-thymus hyperplasia/thymoma
-hyper/hypothroid
-rheumatoid arthritis
-ulcerative colitis
-pernicious anemia
-diabetes mellitus
Bulbar symptoms refer to weakness of muscles innervated by the cranial nerves::
5
7
9
10
11
12
Bulbar symptoms include
-difficulty swallowing (dysphagia)
-difficulty chewing, choking on fluids, nasal regurgitation
-slurring of speech, dysphonia, dysarthria, dysphasia
-difficulty breathing
-weakness of neck muscles
Treatment of MG
Acetylcholinesterase inhibitors (AchEI):
-oral pyridostigmine, less muscarinic SE than neostigmine
-onset: 15-30 min
-peak: 1-2 hours
-duration: 3-4 hours (60mg can last 3-6 hours)
-daily dosage: 30-120mg orally in divided doses
-improves muscle strength for several hours but does not affect the course of the dz
increases concentration of Ach at the postsynaptic membrane
-pyridostigmine: quaternary cannot cross BBB
-other typical symptoms are: diaphoresis, hypersalivation, rhinorrhea, lacrimation, bronchorrhea, bronchospasm, miosis, bradycardia, hypotension
Cholinergic crisis
Other tx for MG
immunosupressants
-corticosteroids (reduced AchR antibody levels)
-cylclosporine
-azathioprine (interferes with production of AchR antibodies)
-plasma exchange patients with respiratory compromise
-IV immune globulin
Thymectomy (Goal is remission or reduction in dosage of medications)
-indicated in patients with thymoma
-thymus gland hyperplasia
-drug resistant MG
-transsternal (open) or video-assisted transcervical
Anesthetic implications for MG
pre op: medication list (steroids, pyridostigmine dose), PFT, abilities to maintain airway, CT/MRI of thymoma, EKG (bradycardia or rhythm issues)
-d/c or taper pyridostigmine dose before sx
-sensitive to sedative medications, aspiration risk (reglan)
-avoid muscle relaxants (TIVA/inhalational and/or regional)
Anectine: resistance or unpredictable (not taking MG meds)or normal/prolonged response (taking MG meds)
NMDR: dramatic sensitivity (decrease in functional receptors) especially when combined with inhalationals
-use of nonopioid analgesia
-patients should be informed that postop ventilation may be needed
-patients with MG are sensitive to NMDBs because of decreased number of postsynaptic receptors at the motor end plate
extubation (safe to extubate?)
reversal: cholinergic crisis, better to use sugammadex
check negative inspiratory force (how well diaphragm is pulling in >30cm H20), head lift, cough, gag, reflex, ensure full return of twitch
Factors which anticipate postoperative mechanical ventilation for MG
-forced vital capacity (FVC) <2.7 liters
-vital capacity < 4mL/kg
-previous hx of myasthenic crisis
-disease duration greater than 6 yrs (Nagelhout 2-6 hours)
-pyridostigmine daily dose of 750mg or more
-COPD
-bulbar symptoms
Postoperative care of MG patient
-non-opioid pain meds
-pulmonary toilet
-avoid meds that depress respiration or delay extubation
-watch for postoperative respiratory failure
-cholingergic vs myasthenic crisis (edrophonium 10mg)
What syndrome acts like MG and what is it associated with?
Lambert-Eaton Myasthenic Snydrome is associated with small cell lung cancer and in contrast to MG, exercise may improve the muscle weakness-related symptoms
What is Lambert-eaton Myasthenic Syndrome (LEMS)?
autoimmune disorder, paraneoplastic (immune-mediated associated with small cell lung ca)
-IgG antibodies are produced and attack pre-synaptic calcium channels (acts similar but different mechanism)
-decreased release of Ach from presynaptic terminals and decreased postjunctional response (muscle weakness)
-number and quality of postjunctional AchRs is unaltered-different from MG
-typically 50-70 yo male complains of proximal extremity weakness (hip and shoulder) that affects gait
-improvement with exercise, no improvement with anticholinesterase or steroids
LEMS presentation
-hip and shoulder weakness, difficulty walking and standing
-autonomic dysfunction with dry mouth reduced sweating and erectile dysfunction, orthostatic hypotension
-sensitive to both depolarizing and non-depolarizers (try to avoid)
-patients presenting with tumor/cancer and weakness..suspect LEMS
-tx with surgery for cancer and/or and 3,4 diaminoyridine
-prednizone and azathioprine can help with symptomes
MG vs Eaton Lambert
Muscular Dystrophies (MD)
hereditary disorders characterized by muscle fiber necrosis and regeneration, leading to muscle degeneration and progressive weakness
Muscular Dystrophies:
-duchenne’’s muscular dystrophy (most common and severe type of MD) 1/3500 live male births
-Becker’s muscular dystrophy (Rare) 1/18,000
-myotonic dystrophy
-limb-girdle
-congenital muscular dystrophy
Congenital Myopathies
-central core disease
-centronuclear myopathy
Duchenne’s muscular distrophy (DMD)
-inherited X-linked recessive disease, the muscles (incl myocardium) are gradually replaced with: fat and connective tissue
-presents in childhood (between 3-5 years of age) as proximal muscle weakness and painless muscle atrophy in boys
-loss of functional dystrophin
proximal muscle weakness and gait issues, gradual onset of muscle wasting, contractures (kyphoscoliosis)
What is dystrophin?
-protein that plays a major role in:
stabilization of the muscle membrane
signaling between cytoskeleton and extracellular matrix
Duchenne Muscular Dystrophy
Duchenne’s Cardiac considerations
-succumb to cardiopulmonary complications by middle age
-cardiomyopathy, mitral regurgitation and rhythm disorders common (tx with ACE inhibitors, diuretics, Beta blockers)—avoid cardiac depressants
-sensitive to myocardial depressant effects of:
-inhalationals
- sedatives
-narcotics
What is consistently elevated in Duchennes muscular dystrophy?
-serum creatinine kinase levels consistently elevated (used to screen newborns. assessment of muscle degeneration)
-as they age, the more the muscle trophies the CK levels begin to decrease
What medication is contraindicated in DMD?
succinylcholine is contraindicated due to risk of :
-hyperkalemia
-rhabdomyolysis
Anesthetic considerations of DMD
-aspiration risk (decreased laryngeal reflexes)
-delayed gastric motility-delayed gastric emptying
-poor respiratory function, pulmonary HTN from chronic sleep apnea, kyphoscoliosis
-increased sensitivity to non-depolarizers
-associated with MH-like response, avoid inhalationals if possible
-recurrent PNA due to ineffective cough and inadequate secretion clearance
-post-operative respiratory failure, restrictive ventilatory pattern
even with recent improvements in supportive care, cardiorespiratory complications cause most of the mortality that occurs before the 4th decade of life
typical EKG abn include an R;S ratio >1 in lead V1; deep Q waves in leads I, aVL, V5 and V6; right axis deviation or R BBB
Becker Muscular Dystrophy
-decrease in normal amounts of dystrophin
-milder disease course than DMD
-onset ~12 yrs
-mortality: similar to DMD but usually live until 5th or 6th decade
Emery-Dreifuss Muscular Dystrophy
-caused by mutations in 2 proteins
-typically presents with contractures of the ankles, elbows, and neck
-progressive weakness of humeral and peroneal muscles
-cardiomyopathy and cardiac conduction abnormalities (present around 30 yrs of age)
Management of Anesthesia (DMD?)
-greatest concerns: cardiac involvement respiratory muscle weakness
-premedication and respiratory depression, impaired swallowing , GI dysfunction
-avoid SCh and inhaled agents: risk for rhabdo and severe hyperkalemia
-sensitive to nondepolarizing muscle relaxants
-preop muscle weakness may require postop mechanical ventilation
-local, regional better alternatives
Myotonia
group of hereditary skeletal muscle diseases (myotonic dytrophy, myotonia congenita, myotonia fluctuans, paramyotonia congenita
common to aLL myotonias: inability of skeletal muscles to relax after chemical or physical stimulation
-dysfunction of ion channels in the muscle membrane
-reduced conductance of cl ions in the sarcolema and other channelopathies
-progressive muscle wasting with weakness combined with multisystem involvement
Myotonic Dystrophy
autosomal dominant disorder (one parent has it) usually occurs in 2nd or 3rd decade of life
-slow progressive deterioration of skeletal, cardiac and smooth muscle, wasting and cardiac conduction defects–death
-characterized by hypoplastic, dystrophic and weak skeletal muscles and prone to persistent contraction
2 types of myotonic dystrophy
1 DM-1 (steinert’s): congenital, childhood onset, adult onset and late onset
2. DM-2- proximal myotonic myopathy and myopathy)
Myotonic Dystrophy (DM-1)
most common type and subdivided by age of onset
intrinsic disorder of skeletal muscle linked to:
-myotonin-protein kinase gene
-defect in Na and CL channel function produces electrical instability of muscle membrane
-characterized by myotonia induced by voluntary or reflex contractions followed by prolonged relaxation
-muscle weakness begins distally and progresses proximally
-manifests as weakness of facial muscles, wasting of sternocleidomastoid muscles, ptosis, dysarthria. dysphagia and inability to relax hand grip
DM-1 (myotonic dystrophy) triad of
- mental retardation (testicular atrophy in men)
- frontal baldness
- cataracts
Considerations of DM-1
-pulmonary issues from hyopotonia, decreased cough effectiveness and chronic aspiration, diminished ventilatory response to hypoxia and hypercapnia, OSA, hypersomnolence
-smooth muscle atrophy, most common is cranial and distal limb muscles (hatchet face)
-conduction defects (heart blocks and tachyarrhythmias)
-sudden cardiac death (3rd degree AV block or ventricular dysrhthmias), respiratory failure or PNA
-hypothyroidism and insulin resistance
-treatment is supportive, NA channel blockers
Myotonic Dystrophy type 2
-similar clinical features as DM-1
-milder than that of DM-1
-AV conduction delays but sudden death less likely
-less likely to have diabetes (Type 1 almost always has DM with it)
-disability from chronic myopathy occurs later
-more likely to have myalgia, muscle strength variation, hypertrophy of calf muscles
-normal life expectancy
Anesthetic considerations of DM-2
=careful with pre0post op sedation (respiratory depression)
-inability to secure airway (jaw muscle spasm)
-avoid Sux and neostigmine? due to its potential to trigger myotonic muscle contraction (myotonic response)
-increased sensitivity to NDMR (Residual block), opioids
-peripheral nerve stimulation may produce myotonia that could be misinterpreted as sustained tetanus
-avoid hypothermia and shivering
-regional
-regional and peripheral blocks
-assume patient has cardiac involvement (pacer available)
-pregnancy exacerbates symptoms (uterine atony, postpartum hemorrhage and retained placenta)
-can use inhalational agents in this patients
-risk of MH no greater than general population
Early signs of MH
- Hypercarbia-unexplained rapid increase in ETCO2
- Muscle rigidity: especially masseter muscle rigidity
- tachycardia: elevated heart rate
Late signs of MH (5-10 minutes later)
- hyperthermia: rapid rise in body temp
- acidosis: metabolic and respiratory acidosis
- rhabdomyolysis: muscle breakdown. leading to elevated CK levels and myoglobinuria
Lab findings of MH
-respiratory/metabolic acidosis
-K>6, CK increase
serum and urine myoglobin increase
Neuroleptic Malignant Syndrome
precise mechanisms unproven
antipsychotic-induced dopamine blockade
sudden drop in CNS dopaminergic activity
nigrostrial pathway-muscle rigidity
-hypothalamus-impaired heat regulation
mesolimbic/mesocortical pathways-altered mental status
Classic Tetrad of clinical signs of NMS
- muscle rigidity (first sign)
- fever
- altered mental status (drowsiness, agitation, confusion, severe delirium and coma)
- autonomic dysfunction (labile BP, tachypnea, tachycardia, diaphoresis, flushing skin, incontinence)
Cause of NMS
-adverse rxn to meds with dopamine-receptor antagonist properties
-MOA: dopamine receptor blockade in the CNS (hypothalamus) leading to dysregulation of temperature and muscle control
-rapid withdrawal of dopaminergic meds
Tx of NMS
-stop offending agent
-supportive measures, benzo or dantrolene
Porphyria
-enzymatic deficiencies in the heme synthesis pathway
-accumulation of neurotoxic porphyrin precursors (porphobilinogen PBG) and aminolevulinic acid (ALA)
-an acute porphyria should be suspected if a patient presents with neurovisceral signs and symptoms and an initial evaluation excludes more common causes
-most important first-line screening test is measurement of urinary porphobilinohen (PBG)
PBG is expected to be substantially increased in all patients during acute porphyria attacks but not in other medical conditions
-PBG test is both sensitive and specific for dx of acute porphyria under most circumstances
an exception is ADP in which ALA and porphyrins but not PBG are elevated
Acute intermittent Porphyria (AIP) Clinical features
-fever, tachycardia, nausea, emesis, severe abd pain, weakness, seizures, confusion and hallucinations
-respiratory failure
-hyponatremia secondary to inappropriate secretion of ADH
young adults and usually women
attacks can last for 2 weeks
What is AIP triggered by?
-hormone changes during menstrual cycle
-fasting
-infection
-exposure to triggering agents (barbiturates, etomidate)
AIP may be considered in patients with unexpected delayed emergency from anesthesia or postop muscle weakness
The circle of Willis connects the ______ and _______ as a major intracranial arterial system.
anterior (carotid)
posterior (vertebrobasilar)
The circle of willis acts to _______________.
provide collateral blood flow between the anterior and posterior circulations of the brain, protecting against ischemia in the event of vessel disease or damage in one or more areas.
Venous drainage to the brain leads to _________.
the internal jugular veins
The cerebral ventricular system is made up of:
4 ventricles that include 2 lateral ventricles (1 in each cerebral hemisphere)
3rd ventricle in the diencephalon
4th ventricle in the hindbrain
inferiorly it is continuous with the central canal of the spinal cord
Role of CSF
protects and maintains the central nervous system by absorbing shock, supplying nutrients , maintaining intracranial pressure, removing waste, controlling temperature, and containing immune cells.
-The fluid-filled ventricles also help keep the brain buoyant and cushioned
CSF is produced by _______________.
ependymal cells in the choroid plexus of the lateral 3rd and 4th ventricles
in adults about ______________ mL of CSF is produced every day.
400-600mL
there is about ______ of CSF at any given time.
150cc
Circulation of CSF
lateral ventricles–>interventricular foramina–>3rd ventricle–>cerebral aqueduct—>4th ventricle–>subarachnoid space via 4 openings in the 4th ventricle
What is CSF reabsorbed by?
arachnoid granulations and drained into the dural venous sinuses of the arachnoid mater into the sinuses with one-way valves
The spinal cord begins at ______________________.
Foramen magnum as a continuation of the medulla oblongata at the base of the skull. It is located within the vertebral or spinal canal.
In men the spinal cord extends up to ________.
45cm
In women, the spinal cord extends up to ___________.
43cm
What is the spinal cord composed of?
longitudinal columns of nuclei (Gray matter) surrounded by ascending and descending tracts (white matter)
The gray matter is butterfly or H-shaped and divided into:
anterior (ventral)
posterior (Dorsal)
lateral (intermediate) horns
Where do somatic and visceral afferent (Sensory) fibers enter the spinal cord?
posterior horns
The gray matter horns divide into:
the white matter into posterior (Dorsal), lateral, and anterior (ventral) columns
The white matter columns include both:
ascending and descending tracts
Ascending neural tracts convey information from _______ to _______.
periphery to brain
Descending tracts convey information from _______ to __________.
brain to periphery
Major ascending tracts include:
- dorsal column (posterior area): conveys tactile sensation, vibration, and proprioception
- spinothalamic tract (anterior): conveys pain, temp and crude touch.
Major descending tracts include:
corticospinal tract: controls find motor movement. Crosses midline at the upper part of midbrain
Where does the anterior spinal artery originate from?
vertebral artery
What does the anterior spinal artery supply?
anterior 2/3 of the spinal cord and medulla
What is the largest radicular artery and the major blood supply to the lower 2/3 of the spinal cord?
Artery of Adamkiewicz (great radicular artery)
Where is the Artery of Adamkiewicz located??
left side between T9-T12.
Where do the 2 posterior spinal arteries originate from?
inferior cerebellar artery, as well as, the segmental spinal arteries (originating from the intercostal and lumbar arteries) supply the posterior 1/3 of spinal cord
Which areas of the spinal cord are more prone to ischemia?
anterior and deep portions of the SC due to fewer anterior medullary feeder vessels than the posterior region and can lead to anterior spinal artery syndrome
What is anterior spinal artery syndrome characterized by?
ischemia of the b/l corticospinal and spinothalamic tracts
This causes loss of motor function and loss of pain and temperature sensation below the level of the lesion
Common etiologies of anterior spinal artery syndrome
aortic dissection
emboli
covering large segments of the thoracoabdominal aorta with endovascular stents
surgical dissection during thoracoabdominal aortic aneurysm repair
What is the main substance used for energy production in the brain?
glucose
Overall metabolic rate for the brain for a young adult is_________.
3.5mL O2/min/100g brain tissue or 5.5 mg glucose/min/100g
skeletal muscle=0.29 ml O2/min/100g
Brain receives ______% CO yet makes up only _____of total body weight.
15%
2%
this disproportionately large blood flow is a result of high metabolic rate of the brain
no anaerobic metabolism, ATP levels zero out around _______.
5 min= cell death
Cerebral perfusion pressure=
CPP=MAP -ICP (CVP substituted fro ICP if higher than ICP)
Decrease in MAP or increase in ICP will ________ CPP.
decrease
What is the Monro-Kellie Doctrine?
describes the relationship between the contents of the cranium and ICP
In non-pathological states, 3 components exist in equilibrium to maintain normal ICP:
-brain tissue
-blood
-CSF
Normal ICP
7-15mmHg
ICP >20mmHg =
substantial redistribution of CSF
at 40-50 mmHg ICP_______________.
vascular structures collapse
ICP >50mmHg =
high risk for herniation
Common presenting symptoms of intracranial HTN include:
-nausea
-vomiting
-headache
-downcast eyes
-papilledema
-altered mental status
and/or
-acute focal neuro deficit
What is the concern with acute Intracranial HTN?
progression to brain herniation
What does the cushings triad include?
- HTN
- Irregular Respirations
- Bradycardia
-reflects severe, increased ICP
What is cerebral autoregulation?
ability of the body to maintain constant CBF despite changes in CPP.
-protects the brain from hypo-or hypoperfusion secondary to decrease or increase in CPP, respectively.
CBF is expected in healthy adults, assuming normal ICP of 10mmHg to be within a MAP of _______ or CPP of _______.
MAP 60-160mmHg
CPP 50-150mmHg
Normally out PaCO@ is ~40mmHg. As this drops, the vasculature _____ dropping CBF by _______________.
constricts dropping CBF by 1-2cc/100g/min for every 1mmHg drop in PaCO2.
very low PaCO2 will significantly drop CBF.
This can be useful in extenuating circumstances (ie. impending brain herniation) but also places the brain at a real risk for ischemia-related damage.
Does PaO2 affect CBF?
really doesnt affect CBF in hyper-oxia. As patient becomes more hypoxemic, CBF will increase once the PaO2 drops below ~40-50mmHg to deliver more blood (and therefore oxygen content ) to the brain
When does PaCo2 correlate with CBF?
when PaCO2 is within the range of 25-70mmHg, it correlates with CBF. 1 mmHg increase in PaCO2 will result in 1-2 mL/100g/min (or 4%) increase in CBF.
The effect of PaCO2 changes in CBF is attenuated after ______.
6 hours. Prolonged hyperventilation should be avoided secondary to the risk of cerebral ischemia
How does Hypothermia affect CMRO2?
hypothermia results in a dose-dependent reduction in CMRO2
How does hyperthermia affect CMRO2?
hyperthermia increases CMRO2, increased uptake of glucose: severe hypoglycemia (blood glucose <2mmol/L or 36mg/dL) results in increased CBF.
How does TBI affect cerebral autoregulation?
cerebral autoregulation is impaired or absent in severe TBI. In these patients, decreases in CPP result in decreases in CBF that may reach ischemic levels and lead to secondary brain injury.
How do cerebral tumors affect cerebral autoregulation?
cerebral tumors are frequently associated with disruption of the BBB, leading to the development of vasogenic edema and increase in ICP. Cerebral autoregulation in peritumurol areas is impaired and these areas are more
How does chronic hypertension affect cerebral autoregulation?
with HTN, cerebral autoregulation curve shifts to the right, BP management should aim to keep MAP within 20-25% of baseline if not monitoring autoregulation specifically
How does preeclampsia affect auto regulation?
endothelial dysfunction, alterations in cerebral blood flow and impaired autoregulation are some of the mechanisms of cerebral edema in preeclampsia.
Aim of Intraoperative neurophysiologic monitoring (IONM)
aims to protect the integrity of the peripheral and CNS during surgical manipulation
SSEPs are sensitive to _________________.
all inhalational agents and nitrous oxide
SSEPs less affected by ________.
IV agents.
__________&___________ increases SSEP amplitude.
Ketamine and etomidate
What do SSEPs monitor?
sensory pathway (through the dorsal root ganglia and posterior column) by electrical stimulation of a peripheral nerve distal to surgery and recording the potential at different landmarks as it propogates along the pathway from the peripheral nerves, through the spinal cord, subcortical and cortical regions
What do MEP’s monitor?
-monitor the motor pathway (including the motor cortex, corticospinal tract, nerve root and peripheral nerve) by transcranial electric stimulation of the motor cortex and recording the elicited muscle contractions by recording electrodes
MEPs are more sensitive to:
the effects of anesthetic agents than SSEPs and MEP changes precede changes in SSEP, allowing time to react
MEPs affected by _______ more than ___________.
affected by inhalational more than IV agents
_______________ can weaken or eliminate MEPs making them unsuitable for use during MEP monitoring.
NMBDs
What do EEG’s monitor?
-cortical electrical activity with surface scalp electrodes or brain surface electrodes to detect cortical ischemia and seizure activity
-can be used to monitor depth of anesthesia
What is the effect of anesthetics on EEG?
dose-dependent and similar to their effect on cortical evoked potentials.
EEGs moderately sensitivity to inhalational agents and insensitive to NMBA
What does EMG monitor?
-monitor nerve roots and peripheral nerves by detecting muscle activity (EMG) or nerve action potentials (NCS)
-spontaneous or free-run EMG provides continuous monitoring and detection of neuronal structures during surgical dissection around nerve roots, cranial and peripheral nerves
-triggered EMG is used to identify and map nerve roots and nerved by delivering stimulation intermittently. It can be used for assessment of pedicle breech during pedicle screw placement.
Do anesthetic agents have effects on EMG?
no
except for NMBas
