Local Anesthetics Flashcards
Local anesthetics definition
Drugs that reversible block conduction of electrical impulses along nerve fibers
Schwann cells
Support and insulate each axon
What type of cells surround each axon
Schwann cells
Unmyelinated nerves and Schwann cells
Small nerves, single Swann cells cover several axons
Myelinated nerves and Schwann cells
Larger nerve, Schwann cell covers only one axon and has several concentric layers of myelin
nodes of ranvier
Periodic segments between Schwann cells along the axon that do not contain myelin
There are VGNa channels in these segments and are the primary site of LA action - action potentials jump from nerve to nerve aka saltatory conduction
What is saltatory conduction
APs jump from nerve to nerve via nodes of ranvier
How many nodes must LAs inhibit VGNa channels in to block impulses
Three successive nerves
What are bundles of axons called
Fasiculi
What are the layers of the connective tissue that cover fasciculi
There are 3
Endoneurium - thin, delicate collagen that embeds the axon in the fascicule
Perineurium - consists of layers of flattened cells that binds groups of fascicules together
Epineurium - surrounds the perineurium and is composed of connective issue that holds fascicles together to form a peripheral nerve
Falyar’s explanation of the neuriums
The endoneuriums surround individual axons
The perineurium binds fasicicles together
The epineurium holds all of those bundles of fascicles together to form a peripheral nerve
RMP of axon
-70mV to -90mV
What physiologic mechanisms help create RMP
Na-K pump in axolemma
Intracellular K ratio of 30:1
Membrane impermeable to other ions
Excess of negatively charged ions in axoplasm
Nernst equation
Expresses the charge created by K+ concentration gradient
What charge puts VGNa into active states (end of depol)
20mV
What restores RMP
NA - K pump
3 Na’s leave for each 2 K’s that enter
LA mechanism of action
Bind to VGNa channels preferentially to those in open, inactive states
They also block K, Ca, and GPCRs to a lesser extent
This blocks transmission of nerve impulses
They DO NOT alter the RMP or threshold potential
Modulated receptor hypothesis of LA action
Preference to attach during active or inactive states
Frequency dependent blockade
Resting nerve is less sensitive to LA than one repeatedly stimulated
AKA = use-dependent or phasic block
“Works better when its doing something”
Are LAs acids or bases? And describe the mechanism of how they enter the cell
All LAs are weak bases
Unionized (unprotonated) base form of the LA diffuses through cell membrane and then becomes re-ionized once inside cell and is able to attach to the inner portion of the VGNa channel
Which type of nerves to LAs preferentially bind to
Smaller, unmyelinated nerves
Aka larger, myelinated nerves are harder to block
Differential blockade order?
Preganglionic (think sympathetic nerves) are blocked first, followed by small C fibers and small A fibers
= loss of pain and temp
Touch and proprioception can still be present
Type A - Alpha fiber characteristics
Proprioception, motor
Diameter = 6-22 um
Heavy myelination
Last to be blocked
Type A beta fiber characteristics
Touch, pressure
Diameter 6-22 um
Heavy myelination
Intermediate time to block
Type A gamma fibers
Muscle tone
Diameter 3-6 um
Heavy myelination
Intermediate time to block
Type A delta fibers
Pain, cold temp, touch
Diameter 1-5 um
Heavy myelination
Intermediate time to block
Type B fiber characteristics
Preganglionic autonomic vasomotor
Diameter <3 um
Light myelination
Blocked early
Type C sympathetic fiber characteristics
Postganglionic vasomotor
Diameter 0.3-1.3um
No myelin
Blocked early
Type C dorsal root fiber characteristics
Pain, warm and cold temp, touch
Diameter 0.4-1.2 um
No myelin
Blocked early
Halsted
Recognized LA as a potential for regional and spinal anesthesia
Koller
Introduced cocaine as the first LA in 1884
LA used for neural blockade structure
3 characteristics
Unsaturated aromatic ring (lipophillic) Tertiary amine (hydrophilic) Ester or abide linkage that binds the aromatic ring to the carbon group (this is how we designate class)
List the amides
Look for the i!!!
Lidocaine Mepivicaine Prilocaine Bupivicaine Ropivacaine Articaine
List the esters
Procaine Chloroprocaine Tetracaine Cocaine Benzocaine
Ester LA metabolism
catalyzed by plasma and tissue cholinesterases via hydrolysis, rapidly occurs throughout body
Amide LA metabolism
Hepatic metab by CYP1A2 and CYP3A4 and thus a significant blood level may develop with rapid absorption
Severe hepatic disease can prolong metab of these drugs and increase risk for toxicity
Which of the classes of LAs have higher allergic potential
Esters because they break down into PABA (para aminobenzoic acid) which is an allergen
What is the longest acting ester LA
Tetracaine
Which of the LA classes are more lipophillic
Amides
Which of the LA classes are more protein bound
Amides
Minimum effective concentration
Cm
The minimum concentration of LA necessary to produce conduction blockade of a nerve impulse
Analogous to MAC
Cm of motor fibers in comparison to sensory fibers
Motor fibers are twice that of sensory fibers
Aka sensory anesthesia may not always be accompanied by paralysis
Do you need more or less LA for intathecal vs epidural anesthesia
You need less
***For epidural you give higher volume of a lesser concentration
What type of nerve fiber is most readily blocked
Pre-ganglionic B fibers
How can you increase onset of LA
Give more
How is the effect of LA terminated
Systemic absorption
Places that are more highly vascularized will last for less time
What increases risk of toxicity of LA
Faster absorption aka highly vascularized area
Good falyar tip for injecting local
Only inject 5ml at a time and aspirate before you inject
If an LA is more lipid soluble, what other characteristics would you expect
Increased protein binding
Increased potency
Longer duration of action
Tendency for severe cardiac toxicity
What plasma proteins do LAs bind to?
Alpha1-acid glycoproteins
To a lesser extent - albumin
Basic drugs become more ionized in what type of solution
A solution where pH is less than pKa
Do drugs with a pKa closer to physiologic pH have a faster or slower onset
Faster
Physiochem properties of Procaine
Pka: 8.9 % ion @ pH 7.4: 97 % protein bound: 6 Onset: slow DoA: 60-90
Onset and doa of chloroprocaine
This one doesn’t intuitively make sense but falyar said its due to the high concentration you give he also said it has a similar profile to procaine but he didn’t list the numbers
Onset: fast
DoA: 30-60
Physiochem props of tetracaine
Pka: 8.5 % ion @ pH 7.4: 93 % protein bound: 94 Onset: slow DoA:180-600 min
Physiochem props of lidocaine
Pka: 7.9 % ion @ pH 7.4: 76 % protein bound: 64 Onset: fast DoA: 90-120min
Onset and doa of mepivicaine
Onset: fast
DoA: 120-240 min
Onset and doa of ropivicaine
Onset: slow
DoA: 180-600 Min
Physiochem props of bupivacaine
Pka: 8.1 % ion @ pH 7.4: 83 % protein bound: 95 Onset: slow DoA: 180-600 mins
Vasomotor action of LAs and exceptions
LA causes relaxation of smooth muscle
Exceptions = lidocaine, ropivacaine, cocaine
Relaxation = vasodilation = decreased doa and increased plasma concentration aka potential toxicity
Rank the uptake of LAs based on regional technique from highest to lowest
IV Tracheal Caudal Paracervical Epidural Brachial Sciatic Subq
Why do we add epi to LA
It’s a vasoconstrictor that decreases rate of vascular absorption
Increased duration and potency of block
Decreased risk of systemic toxicity
Sodium bicarbonate with LAs
Raises pH of LA solution resulting in more drug in the non-ionized state
May result in less pain on injection
Limitation: precipitation can occur
When LA is being distributed, where does it go first
Brain, heart, lungs receive most initially
Risk for toxicity
Then muscle and it receives most
How does renal dysfunction affect LAs
Affects clearance but far less than hepatic failure
But it will affect protein binding
Changes in pregnancy
Mechanical - reduction in epidural spaces
Hormonal - progesterone levels affect LA sensitivity
Local anesthetic systemic toxicity (LAST)
Most commonly occurs from an inadvertent intravacular injection
- initial blocking of inhibitory neurons thought to cause seizures
- blocking of cardiac ion channel = Brady or vib if severe
Presents rapidly
- agitation, tinnitus, circumoral numbness, blurred vision, metallic taste in mouth
- then muscle twitching, unconsciousness, seizures
- if levels are very high = seizures and respiratory arrest
Incident rate is 0.4 per 10,000
-most commonly seen in epidural, axillary, interscalene blocks
How to prevent LAST
Test dosing
Incremental injection with aspiration
Use of pharmacologic markers
Ultrasound
treatment of LAST
Prompt recognition
Airway management
- suppress seizure: benzo and succ
- prevent hypoxia and acidosis
Lipid emulsion therapy
Vasopressors
- epinephrine < 1mg/kg
- no vasopressin
Lipid emulsion dosing
Lipid emulsion 20% - precise volume and flow rate are not crucial
Pt > 70kg
- bolus 100 ml rapid over 2-3 minutes
- gtt 200-250ml over 15-20 minutes
Pt < 70 kg
- bolus 1.5 ml/kg rapid over 2-3 min
- gtt 0.25 ml/kg/min (ideal body weight)
Re-bolus once or twice at the same dose and double infusion rate if patient remains unstable
DOSE LIMIT = 12 ml/kg
Be aware that total volume of lipid emulsion can approach 1 L in a prolonged resuscitation (>30min)
Lipid emulsion therapy moa
Capture local anesthetic in blood (lipid sink)
Increased fatty acid uptake by mitochondria
Interference of Na channel binding
Promotion of calcium entry
Accelerated shunting
Max dose of lidocaine
In mg/kg
No epi: 4
Epi: 7
Max dose of mepivacaine
In mg/kg
No epi: 4
Epi: 7
Max dose of bupivacine
In mg/kg
No epi: 3
Epi: n/a
max dose of ropivacaine
In mg/kg
No epi: 3
Epi: N/A
Max dose of procaine
In mg/kg
No epi: 12
Epi: N/A
Max dose of chloroprocaine
In mg/kg
No epi: 11
Epi: 14
Max dose of prilocaine
In mg/kg
No epi: 7
Epi: 8.5
Max dose of tetracaine
In mg/kg
No epi: 3
Epi: n/a
Amide related allergies
Related to preservative
Paraben, methylparaben, metabisulfite
Methemglobinemia
A conduction of high concentration of methemoglobin in blood
Ferris form of hgb converted to ferric form
Reduced oxygen carrying capacity - hypoxemia not responsive to therapy
Which LAs can cause methemoglobinemia
Benzocaine - rise in cases since 2006 r/t otc spray mostly involving infants <2
Prilocaine - d/t one of its metabolites o-toluidine
- dosing should not exceed 2.5mg/kg
- should be avoided in children under 6, pregnancy, pts taking other oxidizing drugs
Treatment of methemoglobinemia
Methylene blue 1-2 mg/kg over 3-10 minutes
High levels may require transfusion or dialysis
Cauda equina syndrome
Manifests as bowel and bladder dysfunction with lower extremity weakness and sensory impairment related to cord ischemia
- r/f includes supernormal doses of LA
- maldistribution of LA within intrathecal space
Transient neurologic symptoms
Associated with intrathecal lidocaine
Presents as burning, aching, cramp like pain in the low back and radiating down the thighs for up to five days post op
Other risk factors include lithotomy and outpatient surgery
When was lidocaine discovered
1943 by nils Lofgren in sweden
Labor epidural test dose lidocaine concentration
1.5% with epi 1:200,000
Lidocaine and the ACLS algorithm
Why? Depress myocardial automaticity - class IB
Dose?
- 1-1.5 mg/kg IV/IO
- 0.5-0.75 mg/kg (refractory)
- 3 mg/kg total
- 1-4 mg/min or 30-50 mcg/kg/min (maintenance infusion)
EMLA cream
Eutetic mix of LA
1:1 lidocaine:prilocaine
Don’t give
- mucous membranes
- broken skin
- infants < 1 month
- hx methemoglobinemia
Why give lidocaine during induction
Decrease pain of prop
Attenuate CV response to intubation
Attenuate increase in ICP in patients with decreased compliance
Dose on ideal body weight
Lidocaine and pain of propofol
20 mg lidocaine in 10 mL with venous occlusion for 60 seconds
Attenuation of SNS with lidocaine
1.5 mg/kg IV administration 1-3 minutes prior to laryngoscopy
Topical lidocaine (trachea)
Decreases emergence phenomenon aka coughing, sore throat, dysphonia
LTA - administer 30 minutes prior to extubation for best effect
Jelly
Fill cuff with low-dose alkalized lidocaine (40mg) - seeps out over time - need 60 min minutes to achieve desired effect (add bicarbonate to increase non-ionized fraction)
Or just more IV at end of case
Technique for adding alkalized lidocaine to the ETT tube
Achieve correct pressure using air Remove and record amount of air required Add 2ml lidocaine Add 1-2ml sodium bicarbonate Add saline to match cuff volume
USE MANOMETER
Case has to last at least an hour
Airway block
Nebulized lidocaine =.4% lidocaine applied directly to oropharynx
Transtracheal block - 4% lidocaine injected through the cricothyroid membrane
Higher risk of aspiration because pt cannot tell if they are even swallowing or not
Lidocaine infusions
Used as part of multimodal analgesia
Bolus: 1.5 mg/kg bolus dose
Infusion: 2mg/kg/hr
Shown to reduce post op pain and speed up return of bowel function in open and laparoscopic procedures
Decreased pain and improve outcomes in prostatectomy, thoracic, and spine procedures
Accumulation is a concern so monitor patients
Cochrane’s review on lidocaine infusion
Quality of evidence is limited
Benefits uncertain
Bier block
IV regional anesthesia
Indicated for short procedures
25-50ml of 0.5% lidocaine injected into an IV distal to a tourniquet
Onset time 5-10 minutes
Tourniquet pain at 20 minutes
Plasma concentration of lidocaine 1-5 ug/ml effects
Analgesia
Plasma concentration of lidocaine 5-10 ug/ml effects
Circumoral numbness Tinnitus Skeletal muscle twitching Systemic hypotension Myocardial depression
Plasma concentration of lidocaine 10-15ug/ml effect
Seizures unconsciousness
Plasma concentration of lidocaine 15-25ug/ml effect
Apnea coma
Plasma concentration of lidocaine >25ug/ml effect
CV depression
Liposomal local anesthetics: exparel
Injected directly into surgical site shown to reduce opioid requirements for up to 72 hours
Bupivacaine combined with liposomal agent depofoam
Lipid membranes separate chambers of bupivicaine in a honeycomb structure
Administration of exparel
Single dose infiltration only
Admin with a 25g or larger bore needle
Not to exceed 266mg (20ml 1.3% undiluted drug)
- dilute up to 0.89 mg/ml (1:14 by vol)
Invert vial multiple times to re-suspend particles
Inject slowly via infiltration into surgical site with frequent aspiration
Do not admin if its not white
You will need some sort of adjunct to deliver with it because it is going to take a while to start
working - but don’t mix with lidocaine because it will break down the liposome
If you do mix it, use within 4 hours
Exparel what not to do
Don’t
- mix with non-bupivacaine LAs
- use for OB cervical blockade
- give to patients under a8
- use for epidural/intrathecal
- use for peripheral nerve block
- administer if vial has been frozen or exposed to high temp
Do
- use caution for patients with hepatic disease
Adverse effects of exparel
> 10% N/V
<10% dizzy, tachycardia, HA, somnolence, bradycardia, hypoesthesia, lethargy
Cocaine
The original LA and the only one that is naturally occurring
How does cocaine cause SNS stimulation
Blocks monoamine transporter in the adrenergic system which blocks reuptake of catecholamines to cause vasoconstriction
Cocaine use
Primarily used for topical anesthesia of nose and throat
Max dose cocaine
5ml of 5% solution
When should cocaine be used cautiously
Use cautiously with other epi containing solutions, MAOi’s, tricyclics
