LOCAL ANESTHETICS ANESTHESIOLOGY | MIDTERMS (1st Sem)

Dr. Xati M. Talattag

OUTLINE A. NODES OF RANVIER

I. INTRODUCTION  Specialized regions interrupting the myelin sheath at short,
A. Nodes of Ranvier regular intervals.
B. Nonmyelinated Nerve Fibers  Contain densely clustered protein elements essential for
C. Peripheral Nervous Sytem
D. Nerve Fibers
transmission of neuronal signals.
E. Nerve Stimulation  As electrical signals renewed at each node, nerve impulses move
II. MECHANISMS OF LOCAL ANESTHESIA by salutatory conduction.
A. Molecular Mechanism of Local Anesthesia
B. Mechanism of Nerve Blockade
B. NONMYELINATED NERVE FIBERS
C. Differential Blockade
D. Decremental Conduction Model  No nodes of Ranvier
III. CLINICAL USE OF LOCAL ANESTHETICS  Nerve fibers are similarly encased in Schwann cells.
IV. LOCAL ANESTHETICS  Plasma membrane does not wrap around the axons
A. Physiochemical Properties of Local Anesthesia
B. Toxicity of Local Anesthetics concentrically.
V. TREATMENT OF SYSTEMIC TOXICITY FROM LOCAL ANESTHETICS  Several nerve fibers are embedded within a single Schwann cell.
A. Lipid Emulsion
B. Lipid Emulsion for the Treatment of Local Anesthetics C. PERIPHERAL NERVOUS SYSTEM
Cardiovascular Toxicity
VI. TRANSIENT NEUROLOGIC SYMPTOMS  Afferent and efferent fibers
VII. ALLERGIC REACTION TO LOCAL ANESTHETICS o Afferent fibers
VIII. LOCAL ANESTHETICS PRESERVATIVES  Carry sensory stimuli to the CNS (Ascending tract)
Itilicized  Doc’s input o Efferent fibers
 Carry impulses to Effector organs-Effect (Motor-
I. INTRODUCTION Descending tract)
 Bundled into one or more fascicles and organized within three
tissue layers:
1. Endoneurium
 A loose connective tissue containing glial cells,
fibroblast, and blood capillaries, surrounds individual
nerve fibers within each fascicle
2. Perineurium
 Dense layer of collagenous connective tissue surround
each fascicle
3. Epineurium
 A final layer of dense connective tissue encases
groups of fascicles into a cylindrical sheath.

D. NERVE FIBERS
 In general, nerve fibers with cross-sectional diameter greater than
1 μm are myelinated.
 Both a larger nerve size and the presence of myelin sheath are
associated with faster conduction velocity.
 Nerve fibers with large diameters have better intrinsic electric
 Local anesthetics are used to block conductance.
nerves in the system.  Myelin improves the electrical insulation of nerve fibers and
o Peripheral Nervous System permits more rapid impulse transmission via saltatory conduction.
(PNS)  Large-diameter, myelinated fibers, many of which are classified
o Central Nervous System (CNS) as A fibers, are typically involved in motor and sensory function
 Local anesthetics can be in which speed of nerve transmission is critical.
administered thru:  Small-diameter, nonmyelinated C fibers have slower conduction
o Central- neuraxial velocity and relay sensory information such as pain, temperature,
o Peripheral nerve blocks and autonomic functions.
o Local infiltrations in the
peripheral extremeties Table 1. Classification of Nerve Fibers
 Usually done during suturing of lacerations in the Classific Diamet Myelin Conducti Location Function
ER ation er (um) on (m/s)
 Most commonly used is Lidocaine Aα, Aβ 6 - 22 + 30 – 120 Aff/Eff for Motor and
 Myelinated nerve fibers are surrounded by Schwann cells in the muscles and Proprioception
joints
Peripheral Nerve System and by oligodendrocytes in the central
Aγ 3-6 + 15 – 35 Eff to muscle Muscle tone
nervous system. spindle
 The cells form a concentrically wrapped lipid bilayer sheath Aδ 1-4 + 5 – 25 Preganglionic Pain (Sharp)
around the axons that cover the sympathetic Touch
Temp
B <3 + 3 – 15 Postganglioni Autonomic
c sympathetic Function
C 0.3 - - 0.7 – 1.3 Aff Sensory Autonomic
1.3 Nerve function
Pain
Temperature

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E. NERVE STIMULATION
 Under resting conditions, electrical potential of the inside of a
nerve cell is negative with respect to the outside (typically -90mV).
 If this potential is made less negative (depolarization), sodium
channels open and allow sodium ions to enter the cell.
 This influx of positive ions makes the potential inside the
membrane positive with respect to the outside.
 This potential change in turn causes depolarization of the next
segment of membrane, causing more sodium channels to open,
and an electrical impulse, or action potential, propagates.
 Electrical impulses are conducted along nerve fibers as action
potential.
 An action potential is initiated by a local membrane
depolarization.
 When a certain charge threshold is reached, an action potential is
triggered and further depolarization occurs in an “all-or-none”
fashion.
 At low currents, the depolarization is insufficient in all axons.
 As current increases, more and more axons are depolarized to
threshold and the strength of the muscle contraction increases.
 The spike in membrane potential peaks around +50mV at which
point the influx of sodium is replaced with an efflux of potassium
causing a reversal of membrane potential or Repolarization.
 Duration of the action potential is brief (<1msec), because of rapid
inactivation of sodium channels and activation of potassium
channels.
 An action potential also triggers the opening of calcium channels,
allowing calcium ions to penetrate the cell.
 This entry of calcium facilitates release of the neurotransmitter at
the nerve terminal.
 In the absence of a stimulus, voltage-gated sodium channels exist
predominantly in the resting or closed state.
 Depending on the frequency and voltage of the initial depolarizing
stimulus, the channel may undergo either fast or slow inactivation.
II. MECHANISMS OF LOCAL ANESTHESIA
A. MOLECULAR MECHANISM OF LOCAL ANESTHESIA
1. Tonic blockade
 Reflects the reduction in the number of sodium channels for
a given drug concentration present in the open state at
equilibrium.
 There is no motion/ action potential if there is a decrease in
the number of sodium channels.
2. Use-dependent blockade
 Repetitive stimulation of the sodium channels often leads to
a shift in the steady-state equilibrium, resulting in a greater
number of channels being blocked at the same drug
concentration( exact mechanism is incompletely
understood).
 If you use the drug repeatedly, there is more number of
channels blocked.
3. Modulated- receptor theory
 Proposes that local anesthesia bind to the open or
inactivated channels more avidly than the resting channels
suggesting that drug affinity is a function of a channel’s
conformational state.
4. Guarded-Receptor theory
 Assumes that the intrinsic binding affinity remains essentially
constant regardless of a channel’s conformation; rather the
apparent affinity is associated with increased access to the
recognition site resulting from channel gating (inconclusive).
ARAO
Midterms (1st Sem) Local Anesthetics
Dr. Xati M. Talattag
ANESTHESIOLOGY· November 7, 2020
B. MECHANISM OF NERVE BLOCKADE
 Local anesthetics block peripheral nerves by disrupting the
transmission of action potentials along nerve fibers.
 To get to its site of action, principally the voltage- gated sodium
channels, local anesthetics have to reach the targeted nerve
membrane.
o Key target of local anesthetics-VOLTAGE-GATED
SODIUM CHANNELS
 This entails the diffusion of drugs through tissues and the
generation of a concentration gradient.
 Even with close proximity of deposition, only about 1% to 2% of
injected local anesthetics ultimately penetrate into the nerve.
 In peripheral nerve block, when we administer the LA to a certain
area we don’t direct it to the nerve because it will cause nerve
injury. We block the nerve sensation and motor of a certain area
by giving the Las in periphery of the nerve.
 The degree of nerve blockade depends on the local anesthetics
concentration and volume.
Minimal concentration is necessary to effect
complete nerve blockade for a given drug.
Reflects the potency of the local anesthetic and
the intrinsic conduction properties of nerve
fibers which likely depend on the drugs binding
affinity to the ion channels and the degree of drug
saturation necessary to halt the transmission of
action potentials.
 Individuals types of nerve fibers differ in their minimal blocking
concentration such that A fibers are blocked by lower drug
concentrations than C fibers.
The pattern of stimulation (TONIC vs USE-
DEPENDENT BLOCKADE) influences the degree
of conduction failure.
Repetitive stimulations, which can lead to a shift in
steady-state equilibrium of blocked sodium
channels, are associated with higher conduction
failure than TONIC stimulation at a given drug
concentration.
 Sufficient volume is needed to suppress the regeneration of
nerve impulse over a critical length of nerve fiber.
o Ex. Epidural anesthesia- give LA every 30 mins (repeat
adminstration) ---- full anesthesized. Advantage of
epidural anesthesia, you could give it longer (as long as
the duration of the operation) as compared to spinal
anesthesia which last only to 1 ½ hours to 2 hours.
APPLICATION OF LOCAL ANESTHESIA
 Ordered progression of sensory and motor deficits starting
commonly with disappearance of:
1. Temperature sensation
2. Proprioception
3. Motor
4. Sharp pain
5. Light touch
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 Midterms (1st Sem) Local Anesthetics
Dr. Xati M. Talattag
ANESTHESIOLOGY· November 7, 2020

C. DIFFERENTIAL BLOCKADE 4. REGIONAL

 SIZE PRINCIPLE  A regional anatomic approach to anesthesia and analgesia
o Smaller fibers inherently are more susceptible to drug can be used, accomplished either by intravenous
blockade than large fibers administration of local anesthetics to a limb under pneumatic
 Ex. When we want to block only a small portion of the compression (Bier block) or direct application of local
abdomen anesthetics to a set of nerves (nerve blocks).
o Larger myelinated Aδ fibers believed to mediate sharp  For spinal, epidural and peripheral nerve block
pain have been found to be blocked preferentially over small,
nonmyelinated C fibers (dull pain) 5. LOCAL
 Within the C fibers are fast and slow components of impulse  Can be deposited centrally
transmission each with distinct susceptibility to drug blockade. near the nerve roots, either
o C fibers are the fastest because of its fast component intrathecally in the lumbar
 It is may also likely depend on the intrinsic excitatory properties of cistern or epidurally in the
the nerve fibers namely, the patterned expression of voltage- thoracic, lumbar, and caudal
gated sodium channels. regions of the spine.
 2 channels isoforms Nav 1.7 and Nav 1.8 both present on dorsal  Intrathecal through the CSF
root ganglions have been shown to possess different sensitivities (produced in the choroid) area in the spinal canal.
to lidocaine blocked.  Alternatively, injections can be made peripherally at the
plexus, such as the brachial or lumbar plexus block, or on
D. DECREMENTAL CONDUCTION MODEL the nerve fibers.
 As a membrane depolarization from an action potential passively  The duration of the anesthesia and analgesia is dependent
decays with distance along nerve fibers, the presence of local on the type of local anesthetics used, though it can be
anesthetics decrease the ability of adjacent membrane of extended with continuous infusion through an indwelling
successive nodes of Ranvier to regenerate the impulse. catheter.
 Transmission stops once the membrane depolarization falls below
the threshold for action potential activation IV. LOCAL ANESTHETICS
 Made up of a lipid-soluble aromatic-benzene ring connected to a
III. CLINICAL USE OF LOCAL ANESTHETICS amide group via an amide or an ester moiety
 Myriads of uses of local anesthetics in the modern practice of  Type of linkage divides them broadly into 2 categories:
anesthesia 1. Aminoesters - hydrolyzed by plasma cholinesterase
 Ability to attenuate or block pain and other noxious stimuli. 2. Aminoamides - degraded by hepatic carboxylesterase (more
common)
1. TOPICAL
 A eutectic mixture of lidocaine and prilocaine A. PHYSIOCHEMICAL PROPERTIES OF LOCAL ANESTHESIA
 Reduces the sharp, painful sensation associated with needle
insertion and intravenous Table 2. Physiochemical Properties of Local Anesthesia
catheter placement, Local Anesthetic pKa % Protein Binding
particularly in the pediatric AMIDES
population (EMLA). Bupivacaine 8.1 95
 Given also during facial/ derma procedures (cauterization of Etidocaine 7.7 94
facial warts). Lidocaine 7.9 64
Mepivacaine 7.6 77
2. AEROSOL SPRAY Prilocaine 7.9 55
 Aerosolized benzocaine and viscous Ropivacaine 8.1 94
lidocaine ESTERS
 Directed at the mucosal surface can Chloroprocaine 8.7 N/A
help blunt the reflexive response Procaine 8.9 6
associated with airway instrumentation Tetracaine 8.5 94
in an awake patient.  Baricity
 Given in patients that will undergo  Ratio of two densities (CSF and local anesthetic)
endoscopy, bronchoscopy, and awake  Bupivacaine heavy/ hyperbaric
intubation.  Anesthetic is mixed with dextrose
 Used for spinal anesthesia
3. INTRAVENOUS  Denser than the CSF
 Intravenous Lidocaine to decrease the incidence and the  Bupivacaine isobaric
severity of pain associated with propofol administration.  Plain anesthesia, no combination
 Given in MI patients who need to undergo  Used in epidural anesthesia
emergency surgical management.  2 determinants in the spread and duration of local
 Propofol was administered to Michael Jackson anesthetics:
without oxygenation which leads to apnea and 1. Density
caused his death. 2. Dose
 Intravenous Lidocaine also help to reduce the hemodynamic
response to tracheal intubation and extubation. B. TOXICITY OF LOCAL ANESTHETICS
 CENTRAL NERVOUS SYSTEM TOXICITY
o Local anesthetics readily cross the blood-brain barrier
and as a result, CNS toxicity can result from systemic
absorption or inadvertent intravascular injections.
o The effects on the CNS are determined by the plasma
concentration of the local anesthetics.

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 Midterms (1st Sem) Local Anesthetics
Dr. Xati M. Talattag
ANESTHESIOLOGY· November 7, 2020

Table 3. Dose- dependent Systemic Effects of Lidocaine

Plasma Concentration (ug/ml) Effects A. LIPID EMULSION
1-5 Analgesia  Intravenous infusion of lipid emulsion
5-10 Lightheadedness, Tinnitus, o To hasten the return of normal cardiac function.
Numbness of tongue  Reverse bubivacaine- induced asystole
10-15 Seizures, unconsciousness  May act as a plasma “sink” to absorb tissue-bound LA via partition
15-25 Coma, Respiratory arrest principle.
>25 Cardiovascular depression  Lipids may provide usable energy source to bypass the
 When we do circumcision, we can use lidocaine for pediatric impediment
patients. But make sure not to exceed beyond 5mg/kl. B. LIPID EMULSION FOR THE TREATMENT OF LOCAL
 For patients who will undergo liposuction, we can go as high as ANESTHETICS CARDIOVASCULAR TOXICITY
7mg/kl.  Initiate IV bolus of 1.5 cc/kg of 20% lipid emulsion
 Ropivacaine and Levobuvicaine may have a safer  Continue infusion at 0.25cc/kg/min for atleast 10 minutes after the
cardiovascular toxicity profile than Bupivacaine. return of cardiac function.
 If CV instability continues, consider repeating the bolus and
V. TREATMENT OF SYSTEMIC TOXICITY FROM LOCAL increasing the infusion to 0.5 cc/kg/min.
ANESTHETICS
 Up to 10 cc/kg over 30 minutes is the recommended upper limit
 Vigilance and Prevention (best practice) for initial dosing.
 Heart rate, Blood pressure, Oxygenation (should be monitored at
all times) VI. TRANSIENT NEUROLOGIC SYMPTOMS
 Early CNS toxicity maybe manifested by tinnitus or excessive  4-40% incidence of TNS-pain or sensory abnormalities in the
sedation lower back, buttocks or lower extremities after lidocaine spinal
 Treatment of suspected LA toxicity is primarily supportive. anesthesia- associated with other LA but not resulted in
 Oxygenation and ventilation should be maintained and airway, if permanent neurologic injury
necessary must be secured  Potential etiologies:
o Important not only as part or resuscitation but also to prevent o Positioning
further exacerbation of LA toxicity by hypoxemia, o Sciatic nerve stretch
hypercapnia and academia. o Muscle spasm
 Benzodiazepines o Myofascial strain
o Preferred agents to prevent and terminate seizure.  Treatment
o Shown to raise the seizure threshold in animals. o NSAIDs and trigger-point injections
o Ex. Midazolam and Diazepam
 Propofol and Thiopental VII. ALLERGIC REACTION TO LOCAL ANESTHETICS
o Can potentiate the myocardial depression exerted by the  Type I (Immunoglobulin E) hypersensitivity reactions
causative agent at significant doses o Can result in anaphylaxis and potentially life-
o Not best suited for terminating LA-induced seizures threatening
 Succinylcholine or NMBA  Type IV( Celullar Immunity) hypersensitivity reactions
o For prolonged seizure o Delayed type reactions mediated by T lymphocytes
o Can be administered not only to facilitate pulmonary  Symptoms can manifest within 12-48 hours of exposure
ventilation but also to disrupt muscular activity and reduce  Contact dermatitis
the consequent metabolic demand. o Most common presentation
 Muscle relaxants do not reduce electrical excitation in the CNS o Dermal erythema, pruritus,papules, and vesicles
and cerebral metabolic stress continue  Reported reactions- associated with Aminoester agents
 Ephedrine or Epinephrine o Likely due to their metabolism to para-aminobenzoic
o Mild myocardial depression and systemic vasodilation. acid(PABA)  recognized allergen
 Immediate initiation of cardiopulmonary resuscitation for
pending cardiovascular collapse from severe cardiac VIII. LOCAL ANESTHETICS PRESERVATIVES
dysrhythmias. 1. Methylparaben
 Ventricular fibrillation and Cardiac arrest 2. Metabisulfite
o Restore sinus rhythm  Preservative in many LA preparations may also trigger
o Electrocardioversion allergic response
 Preferred Pharmacologic Agents:
o Amiodarone Question and Answer portion:
o Calcium channel and β-adrenergic receptor blocking drugs In cases wherein you need to do cesarean section, what anesthetics
can worsen myocardial function (best avoided) can you give?
o Emergent Cardiopulmonary Bypass  Regional anesthesia (subarachnoid block)
 Considered the only effective life-saving measure for  Faster administration and blockade
otherwise fatal dysrhythmias and cardiac collapse  Epidural Anesthesia
resulting from LA cardiac toxicity.  For patients with comorbidities esp cardiovascular
related
 General anesthesia
 If there are any contraindications in regional
anesthesia
References
 Doc Talattag’s ppt
 Batch 2021 trans

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