LA Part 1 And 2 Flashcards
MOA @ receptor and cellular level of LA
Block Na+ voltage gated channels
Block saltatory conduction
Pool at Nodes of Ranvier on Axon
What type of fibers are blocked first
What type of fibers recover first
Blocked first: small sensory fibers “size principle” then motor fibers; diffusion of LA blocks mantle before motor nerves in the core
Recover first: motor fibers in middle/ very vascular
Equation for acid/base chemicals in aqueous solution
Henderson- Hasselback equation
B + H BH+ (protonated, ionized form, lipid insoluble)
Describe how LA work (non-ionized –> ionized)
B (unprotonated/non ionized) moves through bi lipid layer where it binds with H+ (in axoplasm) to become protonated/ionized so it can bind to the alpha subunit of Na+ voltage gated channels
Has to be unionized to get in and ionized to exert action on alpha subunit
Why don’t LA work well in acidic environment
Too much of LA is ionized and cannot cross bilipid layer.
Describe how NaHCO-3 speeds the onset of a LA
Bicarbonate works as a buffer to speed onset because makes more unprotonated/unionized available to cross into lipid bilayer to get protonated/ionized
Add 1mEq per 10mL LA
What type of channels do the LA typically bind to
Inactivated Na+ channels on alpha subunit
Rapid firing of axon results in increased activated channels (have individual move extremity right after placing block to shorten onset time of block)
Which type of fibers are easily blocked?
Small; myelinated
Which type of fibers are most resistant to LA?
C fibers are most resistant (abundant, slow velocity, contain resistant Na+ voltage gated channels and unmyelinated)
They are the LAST to be blocked
How are mixed nerves blocked?
Smaller/sensory/myelinated fibers of the mantle are blocked first followed by the motor/core fibers.
Which type of pain is the first to disappear?
Fast pain (a delta fibers)
Which type of pain is the most resistant to LA?
Slow pain (type C fibers)
Describe onset to LA in regards to a-alpha, a-beta, delta gamma, B and C nerve fibers.
Recovery is inversely proportional to onset
Onset: B fibers (preganglionic; can’t release NE or E; hypotension occurs)
A delta: pain (fast), cold, touch
A gamma: motor to muscle spindles
A beta: touch, pressure
A alpha: somatic motor; proprioception (muscle spindles, golgi tendon bodies)
C fibers: slow pain/dorsal root/ sympathetic/ post ganglionic
What is the muscle spindle responsible for?
Plays a role in proprioception (where we are in time and space) and is responsible for stretch and speed of stretch
What is the role of Golgi Tendon Bodies?
Plays a role in proprioception (where we are in time and space) and responsible for tension.
Describe order (fastest –> slowest) in which fibers recover, in regards to a alpha, gamma, delta, etc.
C fibers: slow pain
A alpha: somatic, proprioception
A beta: touch pressure
A gamma: motor to muscle spindles; reflex arch
A delta: fast pain (cold, touch)
Preganglionic B Fibers: hypotension ( less of a problem with peripheral nerve block; more of or problem with neuroaxial; paravertebral also can b/c close to neuroaxial)
Why can a patient move their arm before they can feel it?
Motor fibers come back faster than sensory fibers.
Have to be careful because can cause injury, requires splints and immobility devices and patient instruction on post op care.
Which LA are amides?
Amides= 2 “i’s”
Bupivacaine
Ropivicaine
Lidocaine
Which LA are the Esters?
Esters= 1 “i”
Tetracaine
2 chloroprocaine
Novacaine
Describe the R enantiomer and S enantiomer as well as the levorotary and dextrorotary portions.
R enantiomer= caRdiac toxicity
S enantiomer= Safe
Levorotary> potent than Dextrorotary
List LA from greatest vasodilating to least vasodilating.
Lidocaine Bupivicaine Mepivicaine Ropivicaine
The more vasodilating the solution is the more epi will effect it.
Epi will affect Lidocaine more than Ropivicaine
What law is responsible for LA onset??
Fick’s Law ( Rate of Diffusion= Conc. gradient XSurface AreaXdiffusion coefficient/ Membrane thickness)
Describe the 5 Factors that effect the onset of LA
- Lipid solubility
- Concentration
- the higher the concentration the quicker the onset, but the relationship is not linear and will only marginally increase onset; logarithmic - Proximity of the drug to the nerve (diffusion dependent)
- intraneural injections - Physical characteristics of tissue surrounding the nerve
- vascularity, presence of connective tissue, and membrane thickness - pH (lipid solubility): more ionized the less lipid soluble (because can’t get through membrane)
- properties of drug
- tissue
- presence of bicarbonate
How does PKA effect onset?
50% is ionized and 50% unionized
Normal physiologic > ionized than non ionized why bicarbonate helps/ acts as a buffer to get > unionized through lipid bilayer
List the 7 factors effecting LA duration?
- Physical characteristics of drug
- Lipid solubility
- correlation with protein binding but without a direct relationship
- more tightly bound to neural tissue and more difficult to displace
- free form of highly soluble drugs is low (protein bound) –> resistant to metabolism Ex: bupivicaine - Vascularity of tissue
- Nerve being blocked (sciatic vs brachial plexus)
- Presence of vasoconstrictor adjuncts
- Intrinsic vasodilator properties of the drug
- Dose = concentration X volume
- higher dose = longer duration
- concentration has the greatest effect on duration, more so than volume (surgical anesthetic vs. analgesic)
List the LA in order from Fastest onset/duration –> longest onset/duration
Lidocaine 2% Mepivicaine 1.5% Ropivicaine 0.75% Bupivicaine 0.5% Levobupiviaine 0.5% Exparel NA
Little Men Run Backwards
(%’s are for surgical analgesia)
What state are LA pharmacologically active?
Free, unbound state
What are the protein binding compartments?
Alpha 1 acid glycoprotein (high affinity/ low capacity)
Albumin (motor storage reservoir has higher capacity)
How does protein binding correlate to DOA?
Protein binding correlates but is not directly associated with the DOA.
The greater the lipid solubility the greater the protein binding which creates longer duration (resists metabolism)
LA are more likely to highly bind to lipid rich axonal membranes longer
Which 2 populations have less AAG (alpha 1 acid glycoprotein)
Kids
Pregnant Women
Protein binding of LA is concentration and pH dependent? True or false
True: Acidosis and toxicity: small changes in pH cause dramatic changes in level of free drug, this is why LA don’t work in acidic tissues and why acidic people are at risk for LAST.
Malnourished/ low albumin= at higher risk for last
What are the 5 factors associated with the selection of LA?
- Purpose of block
- surgical vs analgesic
- determines concentration used - Volume of LA
- block dependent - Duration desired
- should a catheter be considered? Uncontrolled pain > 24 hrs re evaluate POD #1 - Toxicity issues (ropivicaine best, but not the cheapest)
- Onset and duration
- when is it important? Timing of block
What does mixing short and long acting LA do to the onset and duration?
Mixing LA’s does not change the onset and makes it have significantly shorter DOA.
Don’t do it!
How long is the onset for all PNB
10 minutes
4 things that duration of block dependent on?
Type of block (uptake)
Drug used
Concentration
Adjuncts
Duration of block with ropivicaine and bupivicaine
Long acting 16-24 hours
Duration of block when Mepivicaine used
Intermediate; usually 3 hours
Duration of block when using lidocaine and 2 chloroprocaine
1-2 hours
How does concentration affect block onset and duration
Higher concentration= longer block and shorter onset
3 reasons rescue blocks are done
Block has failed or has nerve sparing properties
Ineffective in providing analgesia or doesn’t cover appropriate dermatome
When the duration of LA has been exceeded
Uptake of Local Anesthetics Based on Regional Anesthetic Technique highest uptake to lowest uptake
In Time I Can Please Everyone But Sally and Susan Intravenous Tracheal Intercostal Caudal Paracervical Epidural Brachial Sciatic Subcutaneous
When are you most likely to see symptoms of LAST?
Majority happens within the first hour; need to monitor patient for 30 minutes after block
Signs first detected with LAST
CNS signs are first signs but if under GA you will not see the CNS signs and will see cardiac signs first
What are the cardiac effects of LAST?
Slow rate of depolarization of Purkinje fibers and ventricular muscle blocking fast Na channels (lengthened PR interval and QRS complex)
What effects do LA have on inotropy?
Dose dependent depression from negative modulation of Ca++ release from SR; vasodilation; decreased inotropy
What do you want to avoid in last; will decrease effect of lipids
Want to avoid acidosis, hypercarbia and hypoxemia
What effect does acidosis have on LAST
Acidosis displaces bupivicaine off protein molecule; most of LA bound to protein 80-85% bound to protein; in acidosis it becomes unbound; free and can bind to cardiac Myocyte
3 medications that decrease threshold even further for cardiac toxicity
Beta blockers, Ca Channel Blockers, and digoxin
What is another name for CNS toxicity signs?
Prodromal signs
What are some patient characteristics that can increase risk of LAST
Extremes of age < 16 or > 60 years
Low muscle mass- neonates, infants and debilitated elderly
Female> male
Comordities
- cardiac disease, esp arrhythmias, conduction abnormalities, ischemia, and CHF
- liver disease
- metabolic disease, especially DM, isovolermeric academia, mitochondrial disease, and carnitine deficiency
- CNS diseases
- Low plasma protein binding- liver disease, malnourished, infants, pregnancy
Which LA has lowest safety margin
Bupivicaine; but LA such as ropivicaine and lidocaine still account for a significant proportion of LAST events
Is seizure more likely in epidural or PNB?
5 x’s more likely in PNB than epidural block
What are prodromal signs?
CNS toxicity, metallic taste, tinnitus, dizziness, confusion, seizure
- not necessarily fatal but he lipids
Signs and symptoms of cardiac toxicity?
Conduction delays, dysrhythmias, bradycardia/hypotension, and cardiac arrest
If LA have direct access to brain how long will it take to see s/sx?
60 seconds
How long will it take if the patient has IV injection
1-5 minutes suggests intermittent IV injection, lower extremity injection or delayed tissue absorption
How do lipids work
Lipids bind to bupivicaine (lipid sink) binds up the liposome and takes it away from cardiac muscle and CNS organs to the liver and increases metabolism and breaks down bupivicaine ofver time
Ways to prevent IV injection
Arterial seizures in carotid circulation; anything above clavicle= brain
Speed of injection, inject slowly
Monitor for prodromal signs
Multiple needle redirections and small aliquot injections 2-3 mL at a time
Aspirating for blood Q 5 mL; look in tubing 2% false negative
Awake and monitoring patient
Use ultrasound (no guarantee)
Epi 2.5-5 mcg/mL= great vascular marker
Why would epi not be a reliable marker for IV injection
If patient takes beta blocker not reliable
What blocks can you not put epi in?
Wrist blocks, finger blocks, toe blocks, ankle block, subgluteal, infragluteal, and subgluteal
Should you put epi in perineural blocks?
No it can decrease blood flow and increase neural toxicity and neural injury
Why can epi cause decrease in diastolic BP
Because beta 2; putting epi in and right around skeletal muscle which has a lot of beta 2 receptors; get some vasodilation
- prolongs duration of block
- prolongs post op analgesia
How does clonidine and dexemetotomidine affect LA
Clonidine: problem because pt gets hypotension
Dexmedetomidine: 1mcg/kg MOA starts to hyperpolarize cell membrane; motor and sensory block significant prolonged with use of alpha 2 agonists
What should the dose be of dexamethasone be if the patient has neuropathy or is a diabetic?
2mg/block; 4 mg/block is fine in patients with no diabetic or neuropathy
Giving 10mg IV can even help extend block duration; give it while pt asleep because scrotal burning
