LOCAL ANAESTHESIA

LOCAL ANAESTHESIADR.VINAY JAIN PG 1ST YEAR1/13/20151DEFINITION Local Anaesthesia is defined as a transient reversible loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerves.(stanley f. malamed)

1/13/20152CLASSIFICATION OF LOCAL ANAESTHESIA1. Esters (of benzoic acid)-Butacaine-Cocaine -Benzocaine-Hexylcaine-Piperocaine-Tetracaine

1/13/20153 Esters (of paraaminobenzoic acid)-Chloroprocaine-Procaine-Propoxycaine

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2. Amides-Articaine-Bupivacaine-Dibucaine-Etidocaine-Lidocaine-Mepivacaine-Prilocaine

3. Quinoline 4. Combinations Lidocaine/Prilocaine(EMLA) Centbucridine

1/13/20155CLASSIFICATION ACCORDING TO DURATION OF ACTION1/13/20156SHORT DURATION (pulpal anesthesia approximately 30 minutes)Lidocaine HCl 2%Mepivacaine HCl 3%Prilocaine HCl 4% (by infiltration)INTERMEDIATE DURATION (pulpal anesthesia approximately 60 minutes)Articaine HCl 4% + epinephrine 1:100,000Lidocaine HCl 2% + epinephrine 1:50,000 and 1:100,000Mepivacaine HCl 2% + levonordefrin 1:20,000Mepivacaine HCl 2% + epinephrine 1:100,000Prilocaine HCl 4% (via nerve block only)LONG DURATION (pulpal anesthesia approximately 90+ minutes)Bupivacaine HCl 0.5% + epinephrine 1:200,000 General StructureA lipophilic groupusually a benzene ringA Hydrophilic groupusually a tertiary amineThese are connected by an intermediate chain that includes an ester or amide linkage

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1/13/20158Ester Amide

Ester linkage is more easy broken Less stable in solutionCannot be stored for long timeMetabolism of most esters results in the production of para aminobenzoate (PABA) which is associated with allergic reaction.

Not broken easyMore stable in solutionStored for long time

Amides, very rarely cause allergic phenomena

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1/13/201510Fundamentals Of Impulse Generation And TransmissionConcept behind action of local anaesthesia- prevent conduction and generation of nerve impulse, set up chemical roadblock between the source of impulse and the brain.NEURON is the fundamental unit of nerve cell.It transmits messages between CNS and all parts of the body.It is of 2 types:-Sensory (afferent)Motor (efferent)1/13/201511Sensory NeuronIt transmits pain sensation with 3 major portions:-Peripheral process (dendritic zone) composed of free nerve endings .The most distal segment of sensory neuron.Axon- Thin cable like structure, has free nerve endings that respond to stimulation produced in the tissues in which they lie provoking an impulse transmitted via axon.Cell Body- located at a distance from axon, provide vital metabolic support for the entire neuron.1/13/201512

1/13/201513Motor NeuronThey transmit nerve impulses from the CNS to the peripheryTheir cell body is interposed between axon and dendrites.Axon branches with each branch ending as a bulbous axon terminal (or button)Axon terminals synapse with muscle cells.1/13/201514Physiology Of Peripheral NervesThe function of nerve is to carry messages from one part of the body to another in the form of electrical action potential called IMPULSES initiated by chemical, mechanical, thermal or electrical stimuli.

Action Potential- Transient depolarization of membrane that result from a brief increase in permeability of the membrane to sodium, and usually also from a delayed increase in permeability of potassium.1/13/201515

ELECTRICAL IMPULSE

1/13/20151616Electrophysiology Of Nerve ConductionNerve possesses a resting potential (step 1) which is negative electrical potential of -70mV because of differing in concentration of ions on either side of membrane.

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RESTING POTENTIAL Internal to the nerve membrane is negative in respect to the outer part.

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STEP 1Stimulation excites the nerve cells.A. Initial phase of slow depolarization, the electrical potential in the nerve becomes slightly less negative.B. When the falling electrical potential reaches a critical level,extremely rapid phase of depolarisation results. This term threshold potential or firing threshold.

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C. This phase of rapid depolarization result in a reversal of the electrical potential across the nerve membrane . Internal to the membrane becomes positive in respect to the outside (+40mV).STEP 2This is a phase of Repolarisation.Electrical potential gradually becomes more negative in respect to the outside until -70mv is achieved.

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Electrochemistry of Nerve ConductionResting State. In its resting state the nerve membrane is Slightly permeable to sodium ions (Na+) Freely permeable to potassium ions (K+) Freely permeable to chloride ions (Cl)

Potassium remains within the axoplasmChloride remains outside the nerve membraneSodium ions remains outside.1/13/201522

Membrane ExcitationDepolarization--Excitation of a nerve segment leads toan increase in permeability of the cell membrane tosodium ions.The rapid influx of sodium ions to the interior of thenerve cell causes depolarization of the nerve membranefrom its resting level to its firing threshold of approximately50 to 60 mV.A decrease in negative transmembrane potential of15 mV (e.g., from 70 to 55 mV) is necessary to reach thefiring threshold.1/13/2015231/13/201524

Exposure of the nerve to a local anesthetic raises its firing threshold. Elevating the firing threshold means that more sodium must pass through the membrane to decrease the negative transmembrane potential to a level where depolarization occurs.Repolarization--The action potential is terminatedwhen the membrane repolarizes. This is caused by theextinction (inactivation) of increased permeability tosodium.1/13/201525Mechanism of action of local anesthetics1. Non-specific membrane expansion theory2. Specific receptor theory

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261/13/201527Non-specific membrane expansion theory: The lipophilic part of the local anaesthetic attaches to the cell membrane to cause swelling. This then reduces the size of the sodium channel to obstruct the flow of sodium ions. This results in a decreased diameter of sodium channels, which leads to an inhibition of both sodium conductance and neural excitation.There is no direct evidence that nerve conduction is entirely blocked by membrane expansion.1/13/201528

1/13/201529Specific receptor theory:

The hydrophilic charged amino terminal binds to specific receptors of the sodium gates to block the passage of sodium ions.Both biochemical and electrophysiological studies have indicated that a specific receptor site for local anesthetic agents exists in the sodium channel either on its external surface or on the internal axoplasmic surface.

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Local anesthetics are classified by ability to reactwith specific receptor sites in the sodium channel1. Within the sodium channel (tertiary amine localanesthetics)2. At the outer surface of the sodium channel (tetrodotoxin, saxitoxin)34. At either the activation or the inactivation gates(scorpion venom)1/13/2015311/13/201532

Drugs in Class C exist only in the uncharged form (RN) Class D drugs exist in both charged and uncharged forms. Approximately 90% of the blocking effects of Class D drugs are caused by the cationic form of the drug; only 10% of blocking action is produced by the base.1/13/201533PHARMACOLOGY OF LOCAL ANESTHESIA

KINETICS OF LOCAL ANESTHETIC ONSETAND DURATION OF ACTIONDiffusion. The rate of diffusion is governed by several factors, the most significant of which is the concentration gradient. The greater the initial concentration of the local anesthetic, the faster is the diffusion of its molecules and the more rapid its onset of action.Blocking Process. After deposition of the local anesthetics close to the nerve as possible, the solution diffuses in all directions according to prevailing concentration gradients.1/13/201534

Induction Time->> Induction time is defined as the period from deposition of the anesthetic solution to complete conduction blockade. Several factors control the induction time Under the operators control are-> the concentration of the drug and the pH of the local anesthetic solution. Factors not under the operators control are-> the diffusion constant of the anesthetic drug and the anatomical diffusion barriers of the nerve.1/13/201535

Effect of PH On LALocal anesthetics are available as salts (usually the hydrochloride) for clinical use. The local anesthetic salt, both water soluble and stable, is dissolved in either sterile water or saline. In this solution it exists simultaneously as uncharged molecules (RN),also called the base, and positively charged molecules (RNH+),called the cation. RNH+ RN + H+Ionic form in the solution varies with the pH of the solution or surrounding tissues.1/13/201536

In the presence of a high concentration of hydrogen ions (low pH), the equilibrium shifts to the left and most of the anesthetic solution exists in cationic form: RNH+ > RN + H+ Hydrogen ion concentration decreases (higher pH),the equilibrium shifts toward the free base form: RNH+ < RN + H+1/13/201537

The relative proportion of ionic forms also depends on the pKa, or dissociation constant, of the specific local anesthetic. The pKa is a measure of a molecules affinity for hydrogen ions (H+). When the pH of the solution has the same value as the pKa of the local anesthetic, exactly 50% of the drug exists in the RNH+ form and 50% in the RN form Henderson-Hasselbalch equation. BASELog ==pHpKa ACID

Benzocaine 3.5 Lidocaine 7.7 Prilocaine 7.7 Articaine 7.8Etidocaine 7.9 Procaine 9.1 1/13/201538

A local anesthetic with a high pKa value has very few molecules available in the RN form at a tissue pH of 7.4.The onset of anesthetic action of this drug is slow because too few base molecules are available to diffuse through the nerve membrane The rate of onset of anesthetic action is related to the pKa of the local anesthetic .A local anesthetic with a lower pKa (Increased lipid solubility permits the anesthetic to penetrate the nerve membrane (which itself is 90% lipid) more easily. This is reflected biologically in the increased potency of the anesthetic. Local anesthetics with greater lipid solubility produce more effective conduction blockade at lower concentrations than the less lipid soluble local anesthetics.1/13/201540

3) The degree of protein binding of the local anesthetic molecule is responsible for the duration of anesthetic activity.In the sodium channel itself, the RNH+ ions bind at the receptor site. Proteins constitute approximately 10% of the nerve membrane, and local anesthetics (e.g., etidocaine, ropivacaine, and bupivacaine) possessing a greater degree of protein binding than others (e.g., procaine) appear to attach more securely to the protein receptor sites and to possess a longer duration of clinical activity.1/13/201541

4)Vasoactivity affects both the anesthetic potency and the duration of anesthesia provided by a drug.Injection of local anesthetics, such as procaine, with greater vasodilating properties increases perfusion of the local site with blood.1/13/201542

Duration of ActionThe duration of action of the drug is also related to the length of the intermediate chain joining the aromatic and amine groups.

Protein binding , Procaine is only 6% protein bound and has a very short duration of action, wherease bupivacaine is 95% protein bound. bupivacaine have a longer duration of action . 1/13/201543

1/13/201544 MAXIMUM DOSES OF LOCAL ANESTHETICSThe doses of local anesthetic drugs are presented in terms of milligrams of drug per unit of body weight.

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1/13/201546Each ml of local anesthesia 1:2,00,000 contains:-Lignocaine hydrochloride 21.3mgAdrenaline 0.0125mgMethylparaben 1.00mgSodium meta bisulfite 0.5mgIn 30ml of local anesthesia, the quantity of lignocaine is approx. 640 mg.According to manufacturer, MRD of lidocaine with vasoconstrictor is 6.6 mg/kg.In a person of weight 60kg MRD is 396 mg . 396/21.3=18.5 ml of LA can be given as a MRD in a person of 60 kg .

Absorption and DistributionAbsorption of local anesthetics is affected by following factors:1)dosage 2)site of injection 3) drug tissue binding 4) presence of vasoconstricting drug The distribution of the drug is influenced by the degree of tissue and plasma binding protein of the drug. The more protein bound the agent, the longer the duration of action, as free drug is more slowly made available for metabolism.

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Metabolism Ester Local Anesthetics. Ester local anesthetics are hydrolyzed in the plasma by the enzyme pseudocholinesterase. The rate of hydrolysis has an impact on the potential toxicity of a local anesthetic.Chloroprocaine, the most rapidly hydrolyzed, is the least toxic, whereas tetracaine, hydrolyzed 16 times more slowly than chloroprocaine, has the greatest potential toxicity.Procaine undergoes hydrolysis to paraaminobenzoic acid (PABA), which is excreted unchanged in the urine

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Amide Local Anesthetics- The biotransformation of amide local anesthetics is more complex than that of the esters. The primary site of biotransformation of amide drugs is the liver.The entire metabolic process occurs in the liver for lidocaine, mepivacaine, articaine,etidocaine, and bupivacaine. Prilocaine undergoes primary metabolism in the liver, with some also possibly occurring in the lung.1/13/201549

ExcretionThe kidneys are the primary excretory organ for both the local anesthetic and its metabolites.Esters appear in only very small concentrations as the parent compound in the urine. This is because they are hydrolyzed almost completely in the plasma.Amides usually are present in the urine as the parent compound in a greater percentage than the esters, primarily because of their more complex process of biotransformation.1/13/201550

Adverse EffectsCNS: excitation followed by depression (drowsiness to unconsciousness and death due to respiratory depression.

Cardiovascular System: bradycardia, heart block, vasodilation (hypotension)

Allergic reactions: allergic dermatitis to anaphylaxis (rare, but occur most often by ester-type drugs). Very uncommonEsters more likely because of p-aminobenzoic acid (allergen)Methylparaben preservative present in amides is also a known allergen

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Clinical Consideration1/13/201552

Properties of ideal LAReversible action. It should be Non-irritant to the tissueIt should not cause any permanent alteration of nerve structure.No allergic reaction.Its systemic toxicity should be low.It should be rapid onset of action.Sufficient duration of action.Stable in solutions.Not expensiveIt should have potency sufficient to give complete anesthesia without the use of harmful concentrated solution.

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Sympathetic block (vasodilatation)(Type B fiber)Loss of pain and temperature sensation(Type C and type A delta)Loss of Proprioception(Type A gamma)Loss of touch and pressure sensation(Type A beta)Loss of motor function(Type A alpha) Sequence of clinical anesthesia

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SIGNS AND SYMPTOMS OF LOCAL ANAESTHETIC TOXICITY:

1-CNS toxicity :

Early or mild toxicity: light-headedness, tinnitus, circumoral numbness, abnormal taste, confusion and drowsiness.

Severe toxicity: tonic-clonic convulsion leading to progressive loss of consciousness, coma,.respiratory depression, and respiratory arrest.

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2-CVS toxicity:

Early or mild toxicity: tachycardia and rise in blood pressure. This will usually only occur if there is adrenaline in the local anaesthetic. If no adrenaline is added then bradycardia with hypotension will occur.

Severe toxicity: Usually about 4 - 7 times the convulsant dose needs to be injected before cardiovascular collapse occurs. Collapse is due to the depressant effect of the local anaesthetic acting directly on the myocardium.1/13/201556ALLERGIC REACTIONS TO LOCAL ANESTHETICSHypersensitivity reactions to local anesthetics are quite rare and generally account for less than 1% of all reported adverse drug reactions.

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Testing for anesthetic allergy using skin testT.R.U.E. Test (thin layer rapid use epicutanous patch test)This is a patch test applied 23 allergens to the skin contained 12 polyester patches.The mixture of anesthetics is called the caine mix, in this Benzocaine, Tetracaine hydrochloride,Dibucaine hydrochloride,1/13/2015581/13/201559

Peel open the package and remove the test panel (Figure 1).

Sign and symptoms of allergic reactionGeneralized body rash or skin rednessItching ,urticariaBronco spasmSwelling of the throatAsthmaAbdominal crampingIrregular heart beatHypotensionSwelling of the face and lips1/13/201560

ADVANTAGES OF LOCAL ANAESTHESIA

During local anesthesia the patient remains conscious

Maintains his own airway.

Excellent muscle relaxant effect.

It requires less skilled nursing care as compared to other anesthesia like general anesthesia.

Non inflammable.

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Less pulmonary complications

Aspiration of gastric contents unlikely.

Less nausea and vomiting.

Contracted bowel so helpful in abdominal and pelvic surgery.

Postoperative analgesia.

There is reduction surgical stress.

Earlier discharge for outpatients.

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Suitable for patients who recently ingested food or fluids.

Local anesthesia is useful for ambulatory patients having minor procedures.

Ideal for procedures in which it is desirable to have the patient awake and cooperative.

Less bleeding.

Expenses are less.

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DISADVANTAGES OF LOCAL ANAESTHESIAThere are individual variations in response to local anesthetic drugs.

Rapid absorption of the drug into the bloodstream can cause severe, potentially fatal reactions.

Apprehension may be increased by the patient's ability to see and hear. Some patients prefer to be unconscious and unaware.

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Direct damage of nerve.

Post-dural headache from CSF leak.

Hypotension and bradycardia through blockade of the sympathetic nervous system.

Not suitable for extremes of ages.

Multiple needle pricks may be needed.

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Contraindications for local anesthesia

- Heart block, second or third degree (without pacemaker)- Severe sinoatrial block (without pacemaker).- Serious adverse drug reaction to lidocaine or amide local anaesthetics.- Concurrent treatment with quinidine, disopyramide, procainamide (class 1 antiarrhythmic agents).- Hypotension not due to arrhythmia.- Bradycardia.

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VASOCONSTRICTORS - Vasoconstrictors are the drugs that constricts the blood vessels and thereby control tissue perfusion.

- They are added to local anaesthesia to oppose the vasodilatory action of local anesthetic agent.1/13/201567

What happens if you dont use a vasoconstrictor?

Plain local anesthetics are vasodilators by nature

1) Blood vessels in the area dilate2) Increase absorption of the local anesthetic into the cardiovascular system (redistribution)3) Higher plasma levels increased risk of toxicity4) Decreased depth and duration of anesthesia diffusion from site5) Increased bleeding due to increased blood perfusion to the area1/13/201568

Why You Need Vasoconstrictors 1) Constrict blood vessels decrease blood flow to the surgical site

2) Cardiovascular absorption is slowed lower anesthetic blood levels

3) Local anesthetic blood levels are lowered lower risk of toxicity

4) Local anesthetic remains around the nerve for longer periods increased duration of anesthesia

5) Decreases bleeding 1/13/201569

Vasoconstrictors should not be used in the following locations

FingersToesNoseEar lobes1/13/201570

Contraindications to Using Vasoconstrictors1) Blood pressure > 200/115 mm Hg

2) Severe cardiovascular disease

3) Acute myocardial infarction in the last 6 months

4) Anginal episodes at rest.

5) Cardiac dysrhythmias that are refractory to drug treatment

6) Patient is in a hyperthyroid state

7) Levonordefrin and Norepinephrine are absolutely contraindicated in patients taking tricyclic antidepressants1/13/201571

Drug InteractionsChloroprocaine epidurally may interfere with the analgesic effects of intrathecal morphine.Opioids and a2 agonists potentiate LAs.Propranolol and cimetidine decrease hepatic blood flow and decrease lidocaine clearance.Pseudocholinesterase inhibitors decrease Ester LA metabolism.Dibucaine (amide LA) inhibits pseudocholinesterase.LA potentiate nondepolarizing muscle relaxant blockade.1/13/20157272

Other agents with LA propertiesMeperidineTCAs (amitriptyline)Volatile anestheticsKetamineTetrodotoxin (blocks Na channels from the outside of the cell membrane) Animal studies suggest that when used in low doses with vasoconstrictors it will significantly prolong duration of action of LA.1/13/20157373

Thanks for your attentions1/13/20157474Steps in Administration of Local Anesthesia 1. Patient should be in supine position. This is preferred because it favors good blood supply and pressure to brain. 2. Syringe aspiration: Before injecting the solution into the body, first a little aspiration in the syringe is done to avoid chances of injecting solution in the blood vessels and consequently preventing toxic effect of local anesthesia. 3. The local anesthetic solution should not be injected into the inflamed and infected tissues to prevent possible spread of infection. In inflamed areas, the local anesthetic solution does not work properly due to acidic medium of inflamed tissues. 4. In every patient, disposable needle and syringe should be used. 5. Before loading syringe the temperature of the solution should be brought to body temperature to make injecting a painless procedure. 6. Before loading the solution in the syringe, it should be confirmed that anesthetic solution is fresh and not expired. 7. Before injecting the local anesthesia, the site of injection should be cleaned free of debris and saliva by a sterile cotton pellet. 8. Topical surface anesthetic solution or jelly may be applied before injecting the needle for painless penetration of needle. 9. Needle should be inserted at the junction of alveolar mucosa and vestibular mucosa and the angle of needle should not be parallel to the long axis of the tooth . Injection parallel to long axis causes more pain (Fig. 15.1). 10. Anesthetic solution is injected slowly not more than 1 ml per minute and in small increments to provide enough time for tissue diffusion of the solution. Needle should be continuously inserted inside till the periosteum or bone is felt by way of slight increase in resistance of the needle movement The needle is slightly withdrawn and here the remaining solution is injected. 11: Two minutes after injection the effect of anesthesia is checked before starting operative procedure. 12. Patient should be carefully watched during and after local anesthesia for about half an hour for delayed reactions 13. After use. the needle and syringe should be discarded in a container.1/13/201575The primary afferent nerve fibres have been divided into seven different groups depending on their function.Aa - Somatic motor and proprioceptionAb - Touch and pressure - circumvent the dorsal horn by giving off collaterals that ascend in the posterior columnsAg - Proprioception, motor to muscle spindlesAd - Pain, cold Toand touch - synapse in Rexed's lamina I of the dorsal horn.B - Autonomic preganglionicCdorsal root- Pain, To, mechanoreception and reflex responses - synapse in Rexed's lamina II (the substantia gelatinosa) of the dorsal horn.Csympathetic- Postganglionic sympatheticsPreferential blockade of a nerve requires a minimal length of fibre exposed to an adequate concentration (Cm) of local anaesthetic. The blocking of three sequential nodes of Ranvier is always sufficient. As thick fibers have an increased distance between nodes of Ranvier this explains the onset of fiber blockadeB - Autonomic preganglionic - vasodilatation with associated decrease in BP.C - Pain and To- loss of thermal appreciationAd - Pain and ToAg - Proprioception - loss of awareness of limbsAb - Touch and pressureAa - Motor

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