Local Anesthetics Flashcards
local anesthetic uses (general) (2)
surgical anesthesia, pain management
peripheral nerve anatomy
axolemma (Na/K pump placement), axoplasm (ICF?), Schwann cells
schwann cells in unmyelinated smaller nerves
single schwann cells cover several axons
schwann cells in myelinated bigger nerves
in larger nerves, the schwann cell covers only one axon and has several concentric layers of myelin
how many successive nodes do you need to block for LA to work
3 successive nodes of ranvier
fasciculi
bundles of axons
3 layers of connective tissue that cover fasciculi
endoneurium, perineurium, epineurium
endoneurium
thin, delicate collagen that embeds axon in the fascicle. will cause a nerve injury if you inject into this.
ex) nerve emerging from C5
perineurium
layers of flattened cells that binds groups of fascicles together
ex) nerve from C5 meeting nerve from C6
epineurium
surrounds perineurium and is composed of connective tissue that holds fascicles together to form peripheral nerve. “holds all bundles together”
Na/K pump in/out ratio?
3 Na out, 2 K in
at which mV is Na at its inactive state
+20mV
LA MOA general
bind to Na channel when in open or inactive states. to lesser extent, also blocks K, Ca, GPCR’s.
(do NOT alter RMP or threshold potential)
diffusion of unionized base across nerve sheath and membrane, re equilibrium between base and cationic forms in axoplasm (joins with H+), binding of cation to receptor inside sodium channel, resulting in inhibition of conduction.
use dependent of phasic block
resting nerve is less sensitive to LA than one being repeatedly stimulated
sensitivity of nerves to LA, small v large
small diameter and lack of myelin enhance sensitivity while larger nerves conduct impulses faster and are harder to block
cascade of blocked fibers in order
preganglionic blocked with low concentrations
small C and A fibers blocked next (loss of pain and temp)
LA’s preferentially bind to smaller/unmyelinated nerves
first sign of LA working
vasodilation
can touch and proprioception still be present
yes, and pain from surgical stimulation can be absent still in this scenario
Type A alpha fiber function, diameter, myelination, block onset
proprioception, motor.
6-22 micrometers
heavily myelinated
last for block onset
Type A beta fiber function, diameter, myelination, block onset
touch, pressure
6-22 micrometers
heavily myelinated
intermediate block onset
Type A gamma fiber function, diameter, myelination, block onset
muscle tone
3-6 micrometers
heavily myelinated
intermediate block onset
Type A delta fiber function, diameter, myelination, block onset
pain, cold, temperature, touch
1-5 micrometers
heavily myelinated
intermediate block onset
Type B fiber function, diameter, myelination, block onset
preganglionic autonomic vasomotor
<3 micrometers
light myelination
early block onset
Type C sympathetic fiber function, diameter, myelination, block onset
postganglionic vasomotor
.3-1.3 micrometers
no myelination
early block onset
Type C dorsal root fiber function, diameter, myelination, block onset
pain, warm, cold temperature, touch
.4-1.2 micrometers
no myelination
early block onset
chemical structure of LA’s
aromatic ring for lipophilicity
tertiary amine (hydrophilic portion of molecule)
either ester or amide linkage binds aromatic ring to carbon group
ester LA’s (5)
procaine chlorprocaine tetracaine cocaine benzocaine
amide LA’s (6)
lidocaine mepivicaine prilocaine bupivicaine ropivicaine articaine
ester metabolism, allergy, DOA, longest acting ester
catalyzed by plasma and tissue cholinesterase via hydrolysis, rapid
if you’re allergic to 1 ester, you’re allergic to all. greater chance of ester allergy than amide because of PABA but still a very small chance
shorter acting due to ready metabolism
longest acting ester is tetracaine
amide metabolism, allergy, DOA, protein binding
metabolism by the liver
last longer for that reason
effect of drug stops when it leaves that part of the body, which is different than it stopping when drug is metabolized
allergy super rare
longer acting because more lipophilic and protein bound. require transport to the liver for metabolism
Cm
minimum concentration of LA necessary to produce conduction blockade of a nerve impulse. analogous with MAC for inhaled anesthetics
Cm of motor fibers is approximately twice that of sensory fibers. sensory anesthesia may not always be accompanied by paralysis.
relationship between absorption of LA, toxicity, and termination of action
systemic absorption results in termination
the slower the LA is absorbed, the less likely there will be toxicity
relationship between concentration of LA and onset
the higher the concentration injected, the faster the onset
lipid solubility correlates with
increased binding
increased potency
longer duration of action
tendency for severe cardiac toxicity
LA bind to (2 proteins)
alpha 1 acid glycoprotein, albumin to a lesser extent
what plays a major role in duration of action for LA’s
injection site
PKa and LA
LA’s are bases that become more ionized when placed in a solution with a pH less than pKa. drugs with pKa closer to physiological pH have faster onset
(chlorprocaine is the exception)
tetracaine pKa, % ionized at physiologic pH, % protein binding, onset, DOA
8.5 93 94 slow 180-600m (use this for a spinal if you run out of bupivicaine. some patients get movement back but they feel numb sometimes still)
lidocaine pKa, % ionized at physiologic pH, % protein binding, onset, DOA
7.9 76 64 fast 90-120m faster onset and less protein binding so used faster/shorter DOA
bupivicaine pKa, % ionized at physiologic pH, % protein binding, onset, DOA
8.1 83 95 slow 180-600 slower onset, more protein binding, longer DOA, more ionized
which drugs won’t vasodilate to the extent of bupivicaine
lidocaine, ropivicaine
what are the implications of relaxation/vasodilation
decreases DOA, increases plasma concentration and potential toxicity because greater vasodilation means increased absorption
total dose of LA determines ________ not _______ or _________
plasma level
volume or concentration
uptake of LA’s based on regional anesthesia, highest to lowest blood concentrations
IV tracheal caudal paracervical epidural brachial sciatic subcutaneous
additives to decrease the rate of absorption
epinephrine sodium bicarbonate clonidine dexmedetomidine opioids ketorolac dexamethasone hyaluronidase
epinephrine for LA
increased duration and potency of block
decreases risk of systemic toxicity
does not prolong block for all LA to same extent
“the shorter acting the drug, the greater the effect you will see with epinephrine”
which drugs are prolonged with epinephrine for local infiltration, peripheral nerve block, and epidural
lidocaine
mepivicaine
procaine
which drugs are prolonged DOA for epinephrine with peripheral nerve block but not epidural
prilocaine and bupivicaine
sodium bicarbonate use, MOA, limitation
used in obstetrics with epidural anesthesia
theoretically raises pH of LA solution resulting in more drug in ionized state
may result in less pain on injection
major limitation is precipitation that can occur
distribution of amide or ester LA
distribution of these are similar
decrease in plasma concentration to highly perfused tissue, based on redistribution
secondary distribution to rest of body, muscle receives most
metabolism of esterases considerations
catalyze hydrolysis of ester LA
procaine and chlorprocaine have plasma half life less than 1 minute
atypical plasma cholinesterase can increase possible toxicity
metabolism of amide LA consideratoins
occurs in liver cia CYP 450
severe hepatic disease can prolong metabolism of this disease
also, consider if they have less protein ex) elderly
renal dysfunction consideration
while renal dysfunction will affect clearance far less than hepatic failure, it will affect the protein binding to both A1AG and albumin
LAST
local anesthetic systemic toxicity
LAST most common reason/pathophys
inadvertent intravascular injection. initial blocking of inhibitory neurons thought to cause seizures. blocking of cardiac ion channels results in bradycardia, vfib most serious complication.
LAST subjective symptoms
tinnitus and metallic taste first, then
agitation, circumoral numbness, blurred vision
muscle twitching, unconsciousness, seizures
very high levels: cardiac and respiratory arrest
LAST most common in which procedures (3)
epidural (puncture vein or dura)
axillary
inter scalene (close to carotid and IJ, this block goes in C7)
LAST prevention strategies
test dosing
incremental injection with aspiration
use of pharmacologic markers
ultrasound
LAST treatment
airway management seizure suppression (benzos, succ) prevent hypoxia and acidosis lipid emulsion therapy epinephrine <1mg/kg
AVOID prop and vasopressin
lipid emulsion dosing
Greater than 70kg
bolus 100mL of 20% over 2-3min
infusion of 200-250ml over 15-20min
Less than 70kg
1.5ml/kg lipid emulsion 20% over 2-3min
.25ml/kg/min IBW
can re bolus to a dosing limit of 12ml/kg
LAST lipid emulsion therapy MOA
- capture local anesthetic in blood (lipid sink, decreases potency of LA)
- increased fatty acid uptake by mitochondria
- interference of Na+ channel binding
- promotion of calcium entry
- accelerated shunting
lidocaine max dose, max dose with epi
4mg/kg
7mg/kg
mepivicaine max dose, max dose with epi
4mg/kg
7mg/kg
bupivicaine max dose, max dose with epi
3mg/kg
NA
ropivicaine max dose, max dose with epi
3mg/kg
NA
procaine max dose, max dose with epi
12mg/kg
NA
Chloroprocaine max dose, max dose with epi
11mg/kg
14mg/kg
Prilocaine max dose, max dose with epi
7mg/kg
8.5mg/kg
Tetracaine max dose, max dose with epi
3mg/kg
NA
what are amide related allergies more commonly associated with
preservatives
ex) paraben, methylparabel, metabisulfite
Methemoglobinemia MOA, drugs, tx
ferris form of HGB (Fe2+) converted to ferric HGB (Fe3+)
Benzocaine Induced involves infants <2y/o
Prilocaine induced is related to metabolites ortho toluidine
tx methylene blue 1-2mg/kg over 3-10min (transient decrease in SpO2)
high levels may require transfusion or HD
Prilocaine dosing, contraindications
dosing should not exceed 2.5mg/kg
avoid in children under 6, pregnant women, patients taking other oxidizing drugs
Cauda Equina Syndrome and risk factors
bowel and bladder dysfunction with LE weakness and sensory impairment related to spinal cord ischemia. risk factors include supernormal doses of LAS or maldistribution of LA within intrathecal space
Transient Neurologic Symptom (TNS)
associated with intrathecal lidocaine, presents as burning, aching, cramp like pain in low back and radiating down thighs for up to 5 days postop. other risk factors include lithotomy position and outpatient surgery
Lidocaine pKa, duration of action, protein binding, metabolism
pKa slightly above physiologic pH, fair amount of nonionized drug
rapid onset but DOA decreased
protein binding 64-70%
metabolism: liver
Lidocaine Solutions Available (7)
.5% 1% 1.5% with epi 1:100,000 1.5% with epi 1:200,000 (labor epidural test dose) 2% 4% 5%
Lidocaine uses (6)
antiarrhythmic topical induction nebulized multimodal pain management regional anesthetic
ACLS algorithm: lidocaine
depresses myocardial automaticity class 1B dose for VT/VF: 1-1.5mg/kg IV/IO .5-.75mg/kg (refractory) 3mg/kg (total) maintenance infusion: 1-4mg/min (30-50mcg/kg/min)
EMLA acronym, mixture, contraindications
Eutetic Mixture of Local Anesthetics
1:1 lidocaine: prilocaine, mixture
contraindicated in mucous membranes, broken skin, infants <1mo, methemoglobinemia hx
Reasons Lidocaine is Given During Induction
decrease pain of propofol, attenuate CV response to intubation, attenuate ICP increase in patients with decreased compliance
Most significant interventions to avoid pain of propofol
AC vein (bigger vein) veno occlusion (lido 20mg in 10ml with tourniquet) small dose of opioids
Lidocaine and attenuation of SNS dosage and positive effects
1.5mg/kg IV 1-3min prior to laryngoscopy attenuates HTN and rise in ICP
2mg/kg completely attenuates cough given 1-5min prior to intubation
Lidocaine and Topical usage
decrease of emergence phenomenon (cough, sore throat, dysphoria)
LTA
lido jelly
filling ETT cuff with jelly (takes 60min, low dose alkalized lido 40mg shown more effective)
(do be aware that additives to lido spray can cause sore throat and hoarseness)
technique for filling ETT with lido jelly
add 2ml lido, 1-2ml NaHCO3-, then saline to match cuff volume
airway block and lidocaine
4% nebulized lido right into oropharynx
or 4% lido injected right into cricothyroid membrane for transtracheal block, if pt coughs it spreads which is good
lidocaine infusions MOA and dosage
multimodal pain management, goal is to use alot less narcotic. usually given in conjunction with mag intraop
1.5mg/kg bolus dose then 2mg/kg/h infusion
Lido infusion MOA, uses related to pain, considerations of infusion
relatively unknown. may involve Na channels, may involve blocking the priming of polymorphonuclear granulocytes
not beneficial for all surgical procedures
shown to reduce postop pain and speed up return of bowel function in open and lap procedures
decrease pain improve functional outcomes in prostatectomy, thoracic and spine procedures
not uncommon to need CV support
Bier Block type of block, indications, dosage, surgical uses
peripheral nerve block, IV regional anesthesia. indicated for short procedures
25-50ml of .5% lido
onset time 5-10 min
tourniquet pain at 20 minutes
in venous system
done for surgeries that are minimally invasive like carpal tunnel
dose dependent effects of lidocaine: plasma concentration of 1-5mcg/ml and its effect
analgesia
dose dependent effects of lidocaine: plasma concentration of 5-10mcg/ml and its effect
circumoral numbness tinnitis skeletal muscle twitching systemic hypotension myocardial depression
dose dependent effects of lidocaine: plasma concentration of 10-15mcg/ml and its effect
seizures
unconsciousness
dose dependent effects of lidocaine: plasma concentration of 15-25mcg/ml and its effect
apnea
coma
dose dependent effects of lidocaine: plasma concentration of >25mcg/ml and its effect
CV depression
Exparel drug, where its injected, DOA
bupivicaine combined with liposomal agent DepoFoam that encapsulates it in honeycomb like structure of numerous aqueous chambers. lipid membrane separate each other.
injected directly into surgical site
provides reduced opioid requirements for up to 72h
Exparel dose, uses, mixing with other drugs, administration considerations, adverse effects
dose based on surgical site and volume required to cover the area. do not exceed 266mg (20ml, 1.3% of undiluted drug).
can be administered either undiluted or diluted up to .89mg/ml (1:14 dilution by volume) with preservative free sterile saline
approved for peripheral nerve blocks in brachial plexus, not approved for all nerve blocks yet
surgeons will use bupivicaine and exparil, remember they’ll need to be bridged to exparil. cannot mix with anything but bupivicaine (lido will break down liposome)
for single dose admin only, administer with 25g or larger bore needly, inject slowly via infiltration into surgical sit e with frequent aspiration to minimize risk of intravascular injection. do not administer if product discolored or if vial has been frozen or exposed to high temperature for an extended period of time. invert vial multiple times to re suspend particles immediately prior to withdrawing drug from vial. use diluted suspensions within 4 hours of preparation in a syringe
>10% can get nausea and vomiting
exparel should not be used for
obstetrical paracervical blockade
patients <18 years old
epidural or intrathecal anesthesia
Cocaine
original LA derived from cocoa plant, only one that is naturally occurring.
has ability to block monoamine transporter in adrenergic system. blocking reuptake of catecholamines results in significant vasoconstriction and sympathetic stimulation.
used primarily for topical anesthsesia of the nose and throat. max dose 5ml in 5% solution
should be used with caution with other epinephrine containing solutions (MAOI’s, TCA’s- r/t catecholamines)
