Local Anesthesia

What is LA (Drug)

Types of LA and Pharmacology

Mechanism of LA

Outline Local Toxicity

What is Local Anesthesia

What is Regional Anesthesia

Anatomy

Types of Regional Anesthesia

LA Drug and
Mechanism
What is Local Anesthetic Drug
• Drug that produces reversible conduction block of the nerve (motor, sensory,
autonomic) impulse
• (LA) are water-soluble salts of lipid-soluble alkaloids. The structure of
local anesthetics comprises a lipophilic aromatic group and a
hydrophilic amino group, bound by an intermediary link
• Sodium channel blockers preventing initiation and propagation of impulse
• All LA vasodilate except cocaine; levobupivacaine and ropivacaine have
bimodal (ie vasodilate at clinical dose, vasoconstrict at subclinical dose)
Mechanism of Action
LA prevent transmission of nerve impulses (conduction
blockade) by inhibiting passage of Na ions through ion-
selective Na Channels in nerve membranes

Na channel : a specific receptor for LA molecules

Failure of Na ion channel permeability to ↑ will slow

the rate of depolarization → threshold potential not
reached → AP not propagated

Does not alter the resting membrane potential or

threshold potential
● smaller fibers are generally more susceptible, because a given volume of
local anesthetic solution can more readily block the requisite number of
sodium channels for impulse transmission to be entirely interrupted.
For these reasons the tiny, rapid-firing autonomic fibers are most
sensitive, followed by sensory fibers and finally somatic motor fibers.1,2
The anesthesiologist blocking mixed spinal nerves is acutely aware of
these differential sensitivities. As patients recover from spinal
anesthesia they first regain voluntary motor function, then sensation
returns, and finally they can micturate (autonomic control)
● QUEST FOR AN «IDEAL" LOCAL ANESTHETIC
There are several properties desirable
in local anesthetics
1. Effective injected or applied topically
2. Short time of onset
3. Duration long enough for the procedure
4. Nonirritating to tissues
5. Nondamaging to nerve structure
6. High margin of safety
7. Soluble in water; stable in solution
8. Sterilizable by autoclaving
Cocaine and synthetic local anesthetics satisfy most of the above criterias
Types and
Pharmacology
-COO-

-NCO-
Ester Amide

Plasma cholinesterase (Faster) Liver (aromatic hydroxylation/ amine

hydrolysis/ N- dealkylation, slower)
=> accumulation in hepatic dysfunction/
reduced hepatic flow

Unstable in solution Stable in solution

More likely to have allergic reactions Less likely to have allergic reactions
(by metabolite para- aminobenzoic acid, PABA) (allergic to additive eg stabilizing agent
methylparaben)
• LA exists in ionised and unionised form
• Weak bases and are mostly ionised at
neutral pH because their pKA are
above 7.4
• Amount of unionised depends on the
pKA of the agent
• The unionised portion of the agent is
lipid soluble, hence diffuse freely
through the phospholipid membrane
of the neuron
Speed of Onset
• The pKA is the pH at which half of the drug is ionised and the other half unionised
• LA exist in equilibrium between ionised form and unionised form
• their pKA and the pH of their surroundings that dictates the percentage of
ionised and unionised form.
• LA with lower pKa (near physiological pH) will have a greater degree of unionised
molecules
→ More LA diffused across membrane
→ rapid onset of action
• Addition of sodium bicarb (bring nearer to pKA)
• Addition of vasocontrictor: lower concentration of vasoconstrictor
→ slower onset
Potency (Lipid solubility)
• Lipophilic nature ensure lipid solubility
• More lipid soluble
--> penetrates membrane more easily
--> less molecule requires for nerve conduction blockade i.e. more potent
Protein Binding
• Bind to α1-acid glycoprotein(protein on sodium channel)
• Higher protein binding is associated with longer duration of action and lower
bioavailability
• Hypoxia, hypercarbia and acidemia decrease protein binding and increase
toxicity
• Children <6 months less protein binding capacity
Factors Affecting LA
• Site (route) of injection and dose – peak plasma concentrations are influenced by ability of tissue to bind
with LA
• Intravenous and tracheal site - more rapid onset
• Subcutaneous and brachial plexus blocks - slower onset of action
• Addition of vasoconstrictor – eg adrenaline (5μg/ml (1:200000))
• All LA are vasodilators except cocaine
• Reduce rate of absorption hence prolongs duration of action and decreases systemic absorption
(prevent toxicity)
• Tissue pH – infection produces acidic tissue and decreases activity of local anaesthetics
• Plasma protein binding is inversely related to the plasma concentration - Decreases in pregnancy, protein
deficiency, neonate, malignancy and increases in sepsis, stress and renal failure
Commonly used LA
Lidocaine
● One of the most frequently used local anesthetics.
● Amide-type anesthetic.
● Quick onset and short duration of action.
● Commonly used for local anesthesia of peripheral nerves, neuraxial
anesthesia, local infiltration, and intravenous regional anesthesia (IVRA)
and
even for topical desensitization of mucosa or skin.
● For surgical anesthesia, concentrations of 1% to 2% are commonly used.
● Also used systemically as an intravenous agent for its analgesic,
antiinflammatory, and antiarrhythmic effect
Bupivacaine
Since its introduction into clinical practice in the early 1960s, bupivacaine
has become one of the most commonly used local anesthetic agents.
● Slow onset of action.
● Significantly longer duration than lidocaine or mepivacaine.
● Bupivacaine is frequently used for nerve blocks and neuraxial anesthesia in
a
● wide range of concentrations (0.125% to 0.75%), allowing for the
development of differential blockade (sensory block without motor block).
● It is significantly more cardiotoxic than other local anesthetic agents
● should an overdose occur, and it should never be used for IVRA
cocaine
-Cocaine solution is widely used by ear, nose and throat surgeons as a local
anaesthetic in the nasal cavity. It is uniquely valuable in this situation
because it combines two actions: a local anaesthetic and a decongestant
effect.

-The mixture of 2 mL of 10% cocaine, 1 mL 1:1000 adrenaline, 2 mL sodium

bicarbonate, and 5 mL sodium chloride makes 10 mL of Moffett’s solution
● Pharmacologically, cocaine blocks re-uptake of noradrenaline and
dopamine in the presynaptic membrane. By increasing levels of
circulating catecholamines, it activates the sympathetic nervous system
and sensitizes target organs such as the heart to sympathetic
stimulation. Although it is used routinely in ENT out-patient clinics, it
should be used with great caution. When the recommended dose is
exceeded, it can be very toxic, causing convulsions and cardiac
dysrhythmias
● Even at subtoxic levels, it has an excitatory and euphoric effect2 that
raises safety concerns for patients attending clinic. Many of these
patients may drive or go back to work after their clinic appointment.
Cocaine is well known as a drug of addiction and has to be stored in
controlled drug cabinets. This adds to the expense of handling and
administration.
● Lidocaine is an effective local anaesthetic on mucosal surfaces and is
used in endoscopy of the respiratory tract. Unfortunately, lidocaine does
not have an intrinsic decongestant effect.More recently, attention has
focused on co-phenylcaine, a solution that contains 5% lidocaine and
0.5% phenylephrine–Phenylephrine is a sympathomimetic agent with
mainly alpha-agonist action; it acts principally as a vasoconstrictor with
minimal effect on the central nervous system or bronchi
Dosage
• Small dose over the longest period of time that achieves adequate
anesthesia
• Risk of ischemia and necrosis at area with limited blood supply
• Digits, penis, tip of nose, earlobe
Agent Dose (with Max single dose Onset (min) Duration of action
vasoconstrictor), (mg) (min), (with
mg/kg vasoconstrictor)

Procaine 8 (10) 1000 20-30 (30- 45)

Chloroprocaine 10- 12 (14) 800 6- 12 30- 60 (60- 90)

Cocaine (nasal) 3 160 3- 5 45- 90

Prilocaine 8 (10) 45 (90)

Lidocaine 3- 5 (7) 300 (2400/ 24hr) 1- 3 30- 120 (120- 240)

Mepivacaine 5 (7) 400 (1000/ 24hr) 3- 20 45- 90 (60- 330)

Bupivacaine 2.5 (3) 175/ 225 (400/ 24hr) 2- 10 130- 175 (180- 480)

Levobupivacaine 2 (3) 150 180- 360

Ropivacaine 2- 3 (3- 4) 225 3- 15 120- 240 (180- 480)

Calculation
○ 100% = 1gram medication in 1ml (1:1)
■ = 1000mg in 1 ml
○ 1% = 1 /100 x 1000mg
■ = 10mg/ ml
■ = 1g in 100ml (1:100)
○ 0.1% = 1mg/ ml = 1: 1 000
○ 0.01% = 0.1 mg in 1ml ie 1mg in 10ml = 1 (g): 10
000(ml)
Concentration (%) Fraction (g: ml) Mg/ ml

100 1:1 1000 in 1

1 1: 100 10 in 1

0.1% 1: 1000 1 in 1

0.01% 1: 10 000 0.1 in 1

(1%= 10mg/ ml)
Bupivacaine 0.5%
= 10/2mg in 1ml
= 5mg in 1ml

(1:1000= 1g in 1000ml)
Adrenaline 1: 200 000
= 1g in 200 000ml
= 1000mg in 200 000ml
= 1/200mg in 1ml
= 0.005mg in 1ml
= 5mcg/ml
Toxicity
Local Toxicity
● Time- , concentration- and drug- dependant manner
● Allergic reaction
○ Para-aminobenzoic acid (PABA): ranging from urticaria to anaphylaxis.
○ The amide class of local anesthetics is far less likely to produce allergic reaction
○ Preservatives (eg methyl- paraben)
● Methemoglobinemia
○ By O- toluidine (metabolite of prilocaine) especially when recommended dose
exceeded
○ Oxidised hemoglobin that shifts O2 dissociation curve to left reducing the ability of
hemoglobin to release O2 to tissue
○ Benzocaine and lidocaine can also cause methemoglobinemia
Systemic Toxicity
● Due to excess plasma concentration of LA in relation to
redistribution to the inactive tissue and clearance by
metabolism
○ Overdose of LA (large dose in regional block)
○ Accidental intravascular injection
○ Repeated/ prolonged infusion
● Increasing blood concentrations of local anaesthetic will result
in progressive signs of local anaesthetic toxicity
● Influenced by dose, site, route of administration
Factors Increasing Risk for Systemic Toxicity
• Hepatic impairment - decreased metabolism of amide LA
• Pregnancy increases CNS sensitivity to local anaesthetics and increases cardiotoxicity
• Overall circulatory state affects systemic absorption and reduce hepatic perfusion
• Renal failure increase volume of distribution of amide LA and increase accumulation of
metabolic by product of LA
• Some drugs (𝛃 blocker and H2 receptor blocker) reduce metabolism of amide LA by
inhibiting Cytochrome P450 2D6 e.g. Metoprolol, Cimetidine, Dextran and reduce hepatic
blood flow
Systemic Toxicity
● carnitine acylcarnitine translocase. The translocase contributes
to the passage of the acyl CoA constituents of the longer fatty
acids across the mitochondrial membranes to the site of their
oxidation. If it is inhibited by local anaesthetics, then fatty acids
will not be fully oxidised, and the heart's adenosine
triphosphate supply will dry up.
Tactics to Reduce Likelihood for Toxicity
● Aspirate prior to injection
● Addition of vasoconstrictor
● Sequential injection of operation site
○ Spread total dose over longer period of time
○ Site to be operated immediately just before operation vs all at once at beginning of operation
● Prolong interval between dosing/ injection
○ In area with highly vascularized area
■ Eg: nasal mucosa, oral mucosa, scalp. Skin of HnN
● Combining more than one LA
○ Short acting + long acting
○ Toxicity of each LA are not additive
○ *caution if using liposomal bupivacaine (Exparel, depobupivacaine) as liposomal carrier might
be disrupted by other LA leading to immediate release in bupivacaine
LA in ENT
 • The regional auricular block @field block
anesthetizes the entire ear except the concha and
meatus that are innervated by the vagus nerve.
The auricle is innervated by the auriculotemporal
nerve superiorly and medially and the greater
auricular nerve and lesser occipital nerve laterally
and inferiorly
• 2-3 mL of lidocaine is injected along the needle tract
• Epinephrine is to be avoided, as the vascular supply
of the cartilage is poor.
nose
Nerve to the Face
1a- supraorbital
1b- supratrochlear
1c- infratrochlear
1d- external (dorsal) nasal

2a- zygomaticotemporal
2b- zygomaticofacial
2c- infraorbital

3a- auriculotemporal
3b- buccal
3c- mental
Nerve to the Face
Superior 1/3rd
Ophthalmic (V1):
1a- supraorbital
1b- supratrochlear

Maxillary (V2):
2a- zygomaticotemporal
Ophthalmic (V1):
1a- supraorbital
- Exits skull at supraorbital notch located at
midpupillary line

1b- supratrochlear
- 1cm medial to supraorbital nerve at its exit
point from supraorbital foramen

Terminal branches of frontal nerve supplying

forehead

*Supratrochlear: more medial coverage and

components of medial nasal dorsum and upper
medial eyelid
Reason for block:
- TnS
- In conjunction with IV sedation
- Postop pain control
- Migraine and chronic headache

How:
- Palpate supraorbital notch at
midpupillary line
- -> inject 1-3ml lateral to medial using
27Fr deep to muscle plane
- Injection carried more medially for
supratrochlear nerve
Maxillary (V2):
2a- zygomaticotemporal
- Terminal branch of V2
- Exits cranium along the lateral
orbital rim and at or 1cm inferior to
lateral canthus

Covers lateral forehead, anterior to

hairline and above the zygoma
How:
- Palpate zygomaticofrontal suture (to
access area behind the lateral orbital rim)
- --> Slide finger into depression just
posterior and inferior to the suture
- --> insert needle posterior to finger and
slide anteriorly to just behind the concave
surface of lateral orbital rim
- --> Instil 1-3mls LA
Nerve to the Face
Middle 1/3rd
Ophthalmic (V1):
1d- external (dorsal) nasal

Maxillary (V2):
2c- Infraorbital
Ophthalmic (V1):
1d- external (dorsal) nasal
- From anterior ethmoidal
(branch of ophthalmic V1)
- Exits skull base at the jnc btn
bony and cartilaginous
junction of the nose

Sensation to nasal dorsum, alae and

vestibule
Reason for block:
- Same as before
- External nasal neuralgia

How:
- Inject into bony cartilaginous jnc in the
subsuperficial musculoaponeurotic
system plane 5mm lateral to midline
- 1-2ml LA
Maxillary (V2):
2c- infraorbital
- Exits skull at infraorbital
foramen (0.5 - 1cm below
midpupillary line)

Sensation to midface (cheek, upper

lips, and lower eyelid)
Reason for block:
- Same as before
- Refractory trigeminal neuralgia isolated to
midface

How (2):
- a) Intraoral
- 1 hand palpate infraorbital rim and retract
cheek to expose gingivobuccal sulcus
adjacent to 2nd premolar
- --> insert needle into gingivobuccal sulcus
and carried 0.5- 1cm below infraorbital rim
at midpupillary line
- 3-5 ml LA
- Careful not to inject into orbit
How (2):
- b) External
- Infraorbital foramen at infraorbital rim
midpupillary line
- --> inject area of infraorbital rim from
skin to below muscle
- Facial artery in close proximity
Nerve to the Face Lower
1/3rd
Mandibular (V3):
2c- mental
- Exits mental foramen btn 1st and
2nd premolar ~ 1cm below gum line
- mid pupillary line (inline with
supraorbital and infraorbital
foramen)
Reason for block:
- Same as before
- Trigeminal neuralgia isolated to lower lip

How:
- Intraoral
- Retract lower lip making mucosa of
gingivobuccal sulcus taut
- --> identify 1st and 2nd premolar
- --> insert needle 1cm below gum line at
45° angle until bony contact is made
- --> withdraw slightly and inject 2- 3ml LA
● For internal nasal approaches, an anesthetic solution with decongestant
is sprayed into the nose with a powered nebulizer; we use topical 4%
lidocaine spray with oxymetazoline or epinephrine. (Of note, both
epinephrine and oxymetazoline are excellent vasoconstrictors, but
phenylephrine should be used with caution.1 )
● Next, pledgets soaked in topical agents are placed within the nasal cavity
to decongest and anesthetize branches of the anterior and posterior
ethmoid, sphenopalatine, and nasopalatine nerves.
Nerve to the Neck
Superior Laryngeal (Internal)
- Enter thyrohyoid
membrane just below the
greater cornu of hyoid bone
Nerve to the Neck
Reason for block:
- Awake fibreoptic
- Laryngeal procedure
- Neurogenic cough

How:
- Patient in supine with head extended
- --> hyoid fixed between the operator’s index
finger and thumb and displaced manually
from side to side
- --> needle passed medially in frontal plane
through skin to contact hyoid at/ near greater
cornu
- --> walk needle caudad until slip off the bone
and advance 2- 3mm (needle enter
paraglottic space)
- --> after 1st give, inject 2-3ml 2% lidocaine
*If blood aspirated, to redirect needle more
anteriorly
source

● A comparison of cocaine and ‘co-phenylcaine’ local anaesthesia in flexible

nasendoscopy J.C. SMITH & T.J. ROCKLEYy Departments of Pharmacy and
yOtolaryngology, Queens Hospital, Burton on Trent, Staffordshire, UK
● Local anesthesia for nasal and sinus surgery FACIAL PLASTIC SURGERY
CLINIC From Midwest Sinus Center, Chicago. Jennifer R. Decker, MD; Jay M.
Dutton, MD, FACS
● Cardio Protective Effects of Lipid Emulsion against Ropivacaine-Induced
Local Anesthetic Systemic Toxicity—An Experimental Study
by Alexandra Elena Lazar 1