LOCALLOCAL

ANAESTHETICSANAESTHETICS

INTRODUCTIONINTRODUCTION► DEFINITIONDEFINITION:- drugs that produce reversible :- drugs that produce reversible

conduction blockade of nerve impulses along conduction blockade of nerve impulses along central and peripheral pathways after regional central and peripheral pathways after regional anaesthesia.anaesthesia.

► HISTORYHISTORY:-:-

Cocaine – 1884Cocaine – 1884 Mepivacaine - 1957Mepivacaine - 1957

Procaine – 1905Procaine – 1905 Prilocaine - 1960Prilocaine - 1960

Tetracaine – 1930Tetracaine – 1930 Bupivacaine - 1963Bupivacaine - 1963

Lidocaine – 1948Lidocaine – 1948 Etidocaine - 1971Etidocaine - 1971

Chlorprocaine – 1955Chlorprocaine – 1955 Ropivacaine - 1992Ropivacaine - 1992

STRUCTURE ACTIVITY STRUCTURE ACTIVITY RELATIONSHIPRELATIONSHIP

AromaticAromatic linkage chainlinkage chain Amine Amine portionportion

ringring

C

O

O R NR1

R2

NH C

O

R N

R1

R2

(Ester linkage)

(Amide linkage)

CLASSIFICATIONCLASSIFICATIONIt is done on the basis of the type of linkage It is done on the basis of the type of linkage

between aromatic and amine portionsbetween aromatic and amine portions

ESTERSESTERS AMIDESAMIDES► ester linkageester linkage amide linkageamide linkage► Metabolized by plasmaMetabolized by plasma metabolized by liver metabolized by liver

pseudocholinesterasespseudocholinesterases cytochromescytochromes► chances of allergic chances of allergic chances of allergic chances of allergic

reaction reactionreaction reaction► systemic toxicitysystemic toxicity more systemic toxicity more systemic toxicity► Slow onset Slow onset moderate to fast onsetmoderate to fast onset

Classes: The rule of “i”Classes: The rule of “i”

► AmAmiidesdes

LLiidocainedocaine

BupBupiivacainevacaine

LevobupLevobupiivacainevacaine

RopRopiivacainevacaine

MepMepiivacainevacaine

EtEtiidocainedocaine

PrPriilocainelocaine

► EstersEsters

ProcaineProcaine

ChloroprocaineChloroprocaine

TetracaineTetracaine

BenzocaineBenzocaine

CocaineCocaine

Mechanism of ActionMechanism of Action

► Blocks the sodium channelBlocks the sodium channel► Wide ranging effects on the nervous systemWide ranging effects on the nervous system

► Local anesthetics blocks the channel from Local anesthetics blocks the channel from the intracellular sidethe intracellular side

► Must enter the neuron to workMust enter the neuron to work► increased lipophilicity is associated with increased increased lipophilicity is associated with increased

potencypotency► Increased un-ionized fraction increases potencyIncreased un-ionized fraction increases potency

The un-ionized molecule crosses the cell membraneThe un-ionized molecule crosses the cell membrane Adding bicarbonate increases the un ionized fractionAdding bicarbonate increases the un ionized fraction

► Tetrodotoxin binds the sodium channel from Tetrodotoxin binds the sodium channel from the outsidethe outside

Sodium ChannelsSodium Channels

► Voltage gated ion Voltage gated ion channelchannel

► 4 segments, each with 6 4 segments, each with 6 transmembrane transmembrane heliceshelices

► Central poreCentral pore

http://courses.washington.edu/conj/membrane/nachan.htm

Sodium ChannelsSodium Channels

► A small machine A small machine with:with:

► Ion selector (very Ion selector (very specific for Na)specific for Na)

► Voltage sensorVoltage sensor 1 in each unit1 in each unit

► Gate connected to Gate connected to voltage sensorvoltage sensor

Opens when Opens when voltage rises, voltage rises, letting Naletting Na++ enter enter cell.cell.

► Inactivation gateInactivation gate Closes when Closes when

voltage gets to +30 voltage gets to +30 mV, ending NamV, ending Na++ flux.flux.

Selectivity Filter

Gate

Inactivation gate

Voltage sensor

Outside

+++++

- - - - -

Inside

70-90mV atrest

http://courses.washington.edu/conj/membrane/nachan.htm

Na channel Na channel conformationsconformations

► 3 channel forms: 3 channel forms: restingresting,, openopen, & , & inactivatedinactivated (1952) (1952) ► NaNa++ ions pass only through ions pass only through openopen channels channels► No NaNo Na++ current through current through channels bound by LAchannels bound by LA► LA binding favored by: LA binding favored by:

DepolarizationDepolarization OpenOpen or or inactivatedinactivated Na channels Na channels Frequent impulses (Frequent impulses (use-use-dependence)dependence)

GR StrichartzBrigham and Women’s Hospital

Harvard Medical School

Site of ActionSite of Action

Selectivity Filter

Gate

Inactivation gate

Voltage sensor

Outside

+++++

- - - - -

Inside

70-90mV atrest

Local Anesthetic

MECHANISM OF ACTIONMECHANISM OF ACTIONPermeates axonal memb in unionized form Permeates axonal memb in unionized form

Reaches voltage gated Na channel by hydrophobic Reaches voltage gated Na channel by hydrophobic approach from within the axonal membapproach from within the axonal memb

Bind to Bind to αα-subunit of Na channel in ionized state-subunit of Na channel in ionized state

Stabilizes channel in inactive state & prevents rapid Stabilizes channel in inactive state & prevents rapid entry of Na ions entry of Na ions

Reduces the amplitude of action potential which Reduces the amplitude of action potential which eventually fails to attain threshold potentialeventually fails to attain threshold potential

Action potential not propogatedAction potential not propogated

reversible conduction blockadereversible conduction blockade

► Frequency dependent block (phasic Frequency dependent block (phasic inhibition):-inhibition):-

Rapidly firing Na channels are Rapidly firing Na channels are more susceptible to blockade by LAmore susceptible to blockade by LA

NervesNerves

►Small diameter nerves are more easily Small diameter nerves are more easily blocked than large diameter nervesblocked than large diameter nerves

►For the same diameter, myelinated For the same diameter, myelinated nerves will be blocked before nerves will be blocked before unmyelinated nerves.unmyelinated nerves.

►Why preganglionic nerves are blocked before the Why preganglionic nerves are blocked before the smaller unmyelinated C fibers (pain nerves) in smaller unmyelinated C fibers (pain nerves) in spinal anesthesia.spinal anesthesia.

►Nerves that fire frequently are Nerves that fire frequently are preferentially blocked over nerves that preferentially blocked over nerves that fire infrequently.fire infrequently.

Nerve SensitivityNerve Sensitivity

1.1. AutonomicAutonomic

2.2. PainPain

3.3. TemperatureTemperature

4.4. TouchTouch

5.5. ProprioceptionProprioception

6.6. Skeletal muscle toneSkeletal muscle tone

Properties that govern Properties that govern clinical effectclinical effect

►PotencyPotency►LipophilicityLipophilicity► Ionization (all are weak bases)Ionization (all are weak bases)►Rate of metabolismRate of metabolism

Rate of OnsetRate of Onset

► PotencyPotency► Correlates closely with lipophilicity, with more lipophilic Correlates closely with lipophilicity, with more lipophilic

local anesthetics being more potentlocal anesthetics being more potent

► DoseDose► Increased dose, either by increasing volume or Increased dose, either by increasing volume or

increasing concentration, accelerates the rate of onsetincreasing concentration, accelerates the rate of onset

► Un-ionized fractionUn-ionized fraction► Adding bicarb accelerates the rate of onsetAdding bicarb accelerates the rate of onset

► EpinephrineEpinephrine► Reduces the rate at which the drug washes awayReduces the rate at which the drug washes away

► PKa. LAs having PKa closer to physiologic Ph PKa. LAs having PKa closer to physiologic Ph 7.4 have fast onset.7.4 have fast onset.

Henderson Hasselbalch Henderson Hasselbalch equationequation

► The basis for understanding this equation is The basis for understanding this equation is knowing the pKa of the agents, remembering that knowing the pKa of the agents, remembering that pKa equals the pH where the ionized and non-pKa equals the pH where the ionized and non-ionized forms are at equilibrium. In other words, ionized forms are at equilibrium. In other words, 50% of each form is present. Local anaesthetics are 50% of each form is present. Local anaesthetics are weak bases. For bases, the pKa - pH relationship is weak bases. For bases, the pKa - pH relationship is described by the Henderson Hasselbalch equation, described by the Henderson Hasselbalch equation, as follows:as follows:

►     pKa - pH= log_pKa - pH= log_ionizedionized    non-ionizednon-ionized

Duration of ActionDuration of Action

► Rate of systemic absorptionRate of systemic absorption► Tissue vascularityTissue vascularity► Use of epinephrineUse of epinephrine

► Rate of eliminationRate of elimination► Particularly for esters, which are metabolized locallyParticularly for esters, which are metabolized locally

► DoseDose► PotencyPotency► General groups:General groups:

► Short: Procaine, chloroprocaineShort: Procaine, chloroprocaine► Intermediate: lidocaine, mepivicaine, prilocaineIntermediate: lidocaine, mepivicaine, prilocaine► Long acting: Tetracaine, bupivacaine, etidocaine, Long acting: Tetracaine, bupivacaine, etidocaine,

ropivacaine, levobupivacaineropivacaine, levobupivacaine

Potency, pKPotency, pKaa, Lipophilicity, Lipophilicity

Drug pKa Octanol /H2OLow Potency

Procaine 8.9 100Intermediate potency

Mepivacaine 7.7 130Prilocaine 8.0 129Chloroprocaine 9.1 810Lidocaine 7.8 366

High potencyTetracaine 8.4 5822Bupivacaine 8.1 3420Etidocaine 7.9 7320Ropivacaine 8.1Levobupivacaine 8.1 3420

Additives and modifiersAdditives and modifiersof LA activityof LA activity

► Increasing doseIncreasing dose: ↓latency of onset; : ↓latency of onset; ↑duration, ↑block success, ↑[LA]↑duration, ↑block success, ↑[LA]

►VasoconstrictorsVasoconstrictors: ↑duration, ↑block : ↑duration, ↑block success, ↓[LA]success, ↓[LA]

►αα22 agonists agonists: ↑duration,↑[LA]: ↑duration,↑[LA]►OpioidsOpioids: ↑duration; permit ↓LA dose: ↑duration; permit ↓LA dose►AlkalinizationAlkalinization (usually NaHCO (usually NaHCO33): ↓latency ): ↓latency

of onset, ↑potencyof onset, ↑potency►PregnancyPregnancy: ↑dermatomal spread, ↑LA : ↑dermatomal spread, ↑LA

potency, ↑free blood [LA]potency, ↑free blood [LA]

Addition of BicarbonateAddition of Bicarbonate

►Lidocaine: 1 cc bicarb / 10 cc drugLidocaine: 1 cc bicarb / 10 cc drug►Mepivacaine: 1 cc bicarb / 10 cc drugMepivacaine: 1 cc bicarb / 10 cc drug►Bupivacaine: 0.1 cc/10 ccBupivacaine: 0.1 cc/10 cc

►Hard to not get precipitationHard to not get precipitation

►Levobupivacaine: same as bupivacaineLevobupivacaine: same as bupivacaine

►Differential sensory/motor blockadeDifferential sensory/motor blockade:-:-

Sensory > motor at lower conc. of Sensory > motor at lower conc. of ropivacaine & bupivacaine ropivacaine & bupivacaine

Useful when selecting an agent for Useful when selecting an agent for ambulatory labour analgesia or post ambulatory labour analgesia or post op analgesia.op analgesia.

► EFFECT OF PREGNANCY ON LA ACTIONEFFECT OF PREGNANCY ON LA ACTION:-:-

sensitivity of nerves to conduction blockade due to sensitivity of nerves to conduction blockade due to progesterone effectprogesterone effect

conc of unbound drug in plasma due to alterations in conc of unbound drug in plasma due to alterations in protein bindingprotein binding

dose required for SA/EA due to reduction in size of dose required for SA/EA due to reduction in size of potential spaces as a result of engorged epidural potential spaces as a result of engorged epidural veins.veins.

Systemic AbsorptionSystemic Absorption

► DoseDose► VascularityVascularity

Intercostal > Caudal > Epidural > Brachial > InfiltrationIntercostal > Caudal > Epidural > Brachial > Infiltration

► pHpH► Slower absorption if solution is alkaline, because more Slower absorption if solution is alkaline, because more

is bound into the tissues.is bound into the tissues.

► LipophilicityLipophilicity► Slower absorption for more lipophilic drugs, again Slower absorption for more lipophilic drugs, again

because more is bound in the tissuesbecause more is bound in the tissues

► EpinephrineEpinephrine► Decreases local blood flow, decreasing absorptionDecreases local blood flow, decreasing absorption

MetabolismMetabolism

► AmidesAmides Primarily hepaticPrimarily hepatic Plasma Plasma

concentration may concentration may accumulate with accumulate with repeated dosesrepeated doses

Toxicity is dose Toxicity is dose related, and may be related, and may be delayed by minutes delayed by minutes or even hours from or even hours from time of dose.time of dose.

► EstersEsters Ester hydrolysis in the Ester hydrolysis in the

plasma by plasma by pseudocholinesterasepseudocholinesterase

Almost no potential for Almost no potential for accumulationaccumulation

Toxicity is either from Toxicity is either from direct IV injectiondirect IV injection

► tetracaine, cocainetetracaine, cocaine

or persistent effects of or persistent effects of exposureexposure

► benzocaine, cocainebenzocaine, cocaine

Some points about individual Some points about individual LALA

►Procaine Procaine ((NovocaineNovocaine))

N

ClO

O N

Rapid onset, rapid offset. Neurotoxic, so not used in spinal anesthesia

Ester Linkage

► Procaine:Procaine: The only indication for its use in dentistry is The only indication for its use in dentistry is

in patients with proven allergy to the amide in patients with proven allergy to the amide group.group.

Used intra-arterially, as part of the Used intra-arterially, as part of the recognized regimen, to treat the recognized regimen, to treat the arteriospasm which might occur during arteriospasm which might occur during intravenous sedation. intravenous sedation.

It has an excellent vasodilatory properties.It has an excellent vasodilatory properties.

Chloroprocaine Chloroprocaine ((NesacaineNesacaine))

N

NO

O

Ester Linkage

Cl

Rapid onset, rapid offset. Neurotoxic, so not used in spinal anesthesia

Benzocaine Benzocaine ((HurricaineHurricaine))

N

O

O

Ester Linkage

Only used topically. Associated with methemoglobinemia, particular as an mucosal spray.

►BenzocaineBenzocaine:: Used mainly as topical, due to its poor Used mainly as topical, due to its poor

water solubility, and because of its low water solubility, and because of its low toxicity, it is used in concentration up to toxicity, it is used in concentration up to 20%.20%.

Hydrolyzed rapidly by plasma esterase to Hydrolyzed rapidly by plasma esterase to p-aminobenzoic acid accounting for its p-aminobenzoic acid accounting for its low toxicity. low toxicity.

Tetracaine Tetracaine ((PontocainePontocaine))

N

O

O

Ester Linkage

N

Slow diffusion in tissues. Often found in topical preparations.

CocaineCocaine

N

O

O

Ester Linkage

O

O

Causes vasoconstriction (as do ropivacaine, bupivacaine, and levobupivacaine).No reason to use. Use 4% lidocaine mixed with 1 ampule (10 mg) phenylephrine instead.

►CocaineCocaine:: The first local anaesthetic agent, rarely The first local anaesthetic agent, rarely

used because of the problems of misuse.used because of the problems of misuse. It is unique in it is ability to produce intense It is unique in it is ability to produce intense

vasoconstriction. Half life 30 minutes.vasoconstriction. Half life 30 minutes. Dosage:Dosage:

►Used as topical 4 – 10% solutionUsed as topical 4 – 10% solution►Maximum dose is 1.5 mg/kg – 100mg max.Maximum dose is 1.5 mg/kg – 100mg max.►Used intranasally . Used intranasally .

Lidocaine Lidocaine ((XylocaineXylocaine))

NN

O

Amide Linkage

LidocaineLidocaine

► amide type anestheticamide type anesthetic► the most commonly used local anestheticthe most commonly used local anesthetic► rapid onset and a duration of 60-75 minutesrapid onset and a duration of 60-75 minutes► extended when solutions with epinephrine extended when solutions with epinephrine

are used for up to 2 hoursare used for up to 2 hours► metabolized in the liver and excreted by the metabolized in the liver and excreted by the

kidneys.kidneys.

Bupivacaine Bupivacaine ((Marcaine, SensoricaineMarcaine, Sensoricaine))

N

N

O

N N

O

S Bupivacaine R Bupivacaine

**

levobupivacaine, Equipotent, but less cardiotoxic than bupivacaine

BUPIVACAINEBUPIVACAINE

►No topical effectNo topical effect►Slow onset and long duration of actionSlow onset and long duration of action►Provide analgesia without significant Provide analgesia without significant

motor blockagemotor blockage►High lipid solubility ,high distribution in High lipid solubility ,high distribution in

tissues d/t protein binding so less in tissues d/t protein binding so less in bloodblood

►Available as 0.25% and 0.50% solutionAvailable as 0.25% and 0.50% solution

N

N

O

*

Ropivacaine Ropivacaine ((NaropinNaropin))

N

N

O

*

Only available as pure S isomerCauses vasoconstrictionLess motor block than bupivacaineOtherwise, equipotent anesthesia, but less cardiotoxic

S bupivacaine

MepivacaineMepivacaine((Carbocaine, PolocaineCarbocaine, Polocaine))

NN

O

►Mepivacaine:Mepivacaine: Possess the least vasodilating effect.Possess the least vasodilating effect. Metabolized in the liver and has Metabolized in the liver and has tt0.50.5 of 120 of 120

minutes.minutes. It’s main indication is when local It’s main indication is when local

anaesthetic without vasoconstrictor is anaesthetic without vasoconstrictor is needed. 3% plain is more effective than needed. 3% plain is more effective than lignocaine.lignocaine.

Onset & duration:Onset & duration:►Rapid onset but slightly shorter duration.Rapid onset but slightly shorter duration.

Etidocaine Etidocaine ((DuranestDuranest))

N

N

O

rapid onset, long effect. Causes profound motor block.

PrilocainePrilocaine

N N

O

Only amide missing a methyl group here.

►Prilocaine:Prilocaine: A very potent local anaesthetic and is less A very potent local anaesthetic and is less

toxic than Lignocaine.toxic than Lignocaine. It produces less vasodilatation than lignocaine It produces less vasodilatation than lignocaine Rate of clearance is higher than other amide-Rate of clearance is higher than other amide-

types, suggesting extra-hepatic metabolism types, suggesting extra-hepatic metabolism with relatively low blood concentration.with relatively low blood concentration.

It’s metabolite o-toluidine lead to methaemo-It’s metabolite o-toluidine lead to methaemo-globinaemia globinaemia (more than 600 mg in adults) (more than 600 mg in adults)

Meperidine Meperidine ((DemerolDemerol))

► Called pethidine Called pethidine ► Probably the Probably the

strangest drug in strangest drug in anesthesiaanesthesia

► opioid, atropinic, opioid, atropinic, local anestheticlocal anesthetic

► blocks seretonin blocks seretonin reuptakereuptake

leading to fatal leading to fatal interactions with interactions with MAO inhibitorsMAO inhibitors

► toxic metabolitetoxic metabolite NormeperidineNormeperidine

► Negative inotropeNegative inotrope

N

OO

Ester Linkage

USES OF LOCAL ANAESTHETICSUSES OF LOCAL ANAESTHETICS

1.1. Topical anaesthesia Topical anaesthesia

2.2. Local infiltrationLocal infiltration

3.3. Peripheral nerve blockPeripheral nerve block

4.4. I.V. regional anaesthesiaI.V. regional anaesthesia

5.5. Spinal anaesthesiaSpinal anaesthesia

6.6. Epidural anaesthesiaEpidural anaesthesia

► TOPICAL ANAESTHESIATOPICAL ANAESTHESIA:-:-

LA placed on mucous membrane or skinLA placed on mucous membrane or skin Cocaine is commonly used for rhinolaryngologic Cocaine is commonly used for rhinolaryngologic

procedures due to vasoconstricting effectprocedures due to vasoconstricting effect Lox-oxymetazoline combination is equally effectiveLox-oxymetazoline combination is equally effective Nebulized lox used for surface anaesthesia for Nebulized lox used for surface anaesthesia for

fiberoptic laryngoscopy/bronchoscopyfiberoptic laryngoscopy/bronchoscopy May cause bronchoconstriction in asthmaticsMay cause bronchoconstriction in asthmatics Rapid absorption of LA from these mucosal sites Rapid absorption of LA from these mucosal sites

and blood conc achieved are similar to i.v. routeand blood conc achieved are similar to i.v. route Synera: Synera: lox+tetracaine with heating element for lox+tetracaine with heating element for

intact skin anaesthesiaintact skin anaesthesia TAC:TAC: tetracaine+ adrenaline+ cocaine tetracaine+ adrenaline+ cocaine

anaesthesia through cut skin in anaesthesia through cut skin in childrenchildren

LET: LET: lox+ epi+ tetracaine (subs of TAC)lox+ epi+ tetracaine (subs of TAC)

► EMLAEMLA:- Eutectic mixture of local anaesthetics:- Eutectic mixture of local anaesthetics 2.5% lox + 2.5% prilocaine2.5% lox + 2.5% prilocaine Diffuse through intact skin to block neuronal Diffuse through intact skin to block neuronal

transmission from dermal receptorstransmission from dermal receptors Dose- 1-2 gm per 10 cm² area under occlusive Dose- 1-2 gm per 10 cm² area under occlusive

dressingdressing Used for skin graft harvesting, i.v.cannulation, Used for skin graft harvesting, i.v.cannulation,

cauterising genital warts, circumcisioncauterising genital warts, circumcision To be applied 45-60 min prior to procedureTo be applied 45-60 min prior to procedure Low frequency USG speeds the onsetLow frequency USG speeds the onset Side effects:- skin reactions like pruritus, edema, Side effects:- skin reactions like pruritus, edema,

erythema and rasherythema and rash

may cause methemoglobinemia in may cause methemoglobinemia in children<3 mth or patients on oxidising drugs like children<3 mth or patients on oxidising drugs like sulphonamides, paracetamol, phenytoin, NTG.sulphonamides, paracetamol, phenytoin, NTG.

► LOCAL INFILTRATIONLOCAL INFILTRATION:- :-

Extravascular placement of anaesthetic in the Extravascular placement of anaesthetic in the area to be anaesthetizedarea to be anaesthetized

Choice of agent depends on the desired duration Choice of agent depends on the desired duration

Lignocaine is the most commonly used agentLignocaine is the most commonly used agent

Duration may be significantly increased by Duration may be significantly increased by adding adding

1:200000 epinephrine1:200000 epinephrine

► PERIPHERAL NERVE BLOCKSPERIPHERAL NERVE BLOCKS:-:-

LA injected in the vicinity of peripheral nerve or plexusLA injected in the vicinity of peripheral nerve or plexus LA diffuse from mantle to core across a conc gradientLA diffuse from mantle to core across a conc gradient Proximal anatomic structures are first to be Proximal anatomic structures are first to be

anaesthetized and first to regain sensationanaesthetized and first to regain sensation Sequence of onset & recovery in a mixed nerve Sequence of onset & recovery in a mixed nerve

depends more on the anatomic location of the fibresdepends more on the anatomic location of the fibres Dose required is lesser if USG guided blocks are used Dose required is lesser if USG guided blocks are used

as the LA is placed in the immediate perineural areaas the LA is placed in the immediate perineural area Long acting amide LA like bupivacaine and Long acting amide LA like bupivacaine and

ropivacaine are preffered as they provide analgesia ropivacaine are preffered as they provide analgesia for upto 12 hrs.for upto 12 hrs.

Ropivacaine may prove to be a better choice Ropivacaine may prove to be a better choice ►Shorter duration of motor blockShorter duration of motor block►Less cardiovascular side effectsLess cardiovascular side effects

► I.V. REGIONAL ANAESTHESIA (IVRA)I.V. REGIONAL ANAESTHESIA (IVRA):-:-

LA injected i.v. in a torniquet occluded limbLA injected i.v. in a torniquet occluded limb

LA diffuses from vascular bed to non vascular tissues LA diffuses from vascular bed to non vascular tissues

like axons &nerve endings leading to conduction like axons &nerve endings leading to conduction

blockadeblockade

Occluding torniquet is gradually releasedOccluding torniquet is gradually released

Prilocaine attains lower blood conc as compared to Prilocaine attains lower blood conc as compared to

lignocaine when administered in equal doseslignocaine when administered in equal doses

Dose of lignocaine- 3 mg/Kg (40 ml of 0.5% solution)Dose of lignocaine- 3 mg/Kg (40 ml of 0.5% solution)

Chlorprocaine, bupivacaine & ropivacaine not Chlorprocaine, bupivacaine & ropivacaine not

recommended for IVRArecommended for IVRA

► SPINAL ANAESTHESIASPINAL ANAESTHESIA:-:-

LA injected in the lumbar subarachnoid spaceLA injected in the lumbar subarachnoid space Site of action: preganglionic fibres as they leave the Site of action: preganglionic fibres as they leave the

spinal cord in the anterior ramispinal cord in the anterior rami Differential zones of autonomic, sensory & motor Differential zones of autonomic, sensory & motor

blockblock Total dose of LA more imp than the volume/conc.Total dose of LA more imp than the volume/conc. Hyperbaric solutions produce more dense blockHyperbaric solutions produce more dense block Duration depends mainly on systemic absorption for Duration depends mainly on systemic absorption for

both ester & amide LAboth ester & amide LA Dose of lox to be limited to 60 mg to prevent TNSDose of lox to be limited to 60 mg to prevent TNS Side effects:Side effects:

► HypotensionHypotension► BradycardiaBradycardia► Cardiac arrestCardiac arrest► Respiratory depression & apnea Respiratory depression & apnea

► EPIDURAL ANAESTHESIAEPIDURAL ANAESTHESIA:-:- LA placed in epidural/sacral caudal spaceLA placed in epidural/sacral caudal space

LA diffuses in paravertebral area and across the dura LA diffuses in paravertebral area and across the dura

to act on nerve roots & spinal cordto act on nerve roots & spinal cord

Delayed onset as compared to SADelayed onset as compared to SA

Zone of differential motor blockade extends four Zone of differential motor blockade extends four

segments below the sensory levelsegments below the sensory level

Addition of epinephrine may lead to 1/3 reduction in Addition of epinephrine may lead to 1/3 reduction in

systemic absorptionsystemic absorption

Long acting amide LA in lower conc may be used for Long acting amide LA in lower conc may be used for

post op analgesia and labour analgesia without post op analgesia and labour analgesia without

producing significant motor paralysisproducing significant motor paralysis

► OTHER USESOTHER USES:-:-

1.1. AnalgesiaAnalgesia:: lidocaine as continuous infusion to lidocaine as continuous infusion to

maintain a plasma conc 1-2 ug/ml. effective in maintain a plasma conc 1-2 ug/ml. effective in

post op pain & stump pain.post op pain & stump pain.

2.2. Cough suppressantCough suppressant:: i.v. lignocaine in i.v. lignocaine in

perioperative periodperioperative period

3.3. Anti arrythmicAnti arrythmic: i.v. lignocaine (class I B drug) : i.v. lignocaine (class I B drug)

used in a dose of 1.5mg/Kgused in a dose of 1.5mg/Kg

4.4. Anti epilepticAnti epileptic: suppression of grand mal : suppression of grand mal

seizuresseizures

5.5. Bronchodilation Bronchodilation

► Antiinflammatory EffectsAntiinflammatory Effects: following : following mechanismsmechanisms

Inhibit PAFInhibit PAF Inhibit G proteinInhibit G protein Inhibit neutrophil accumulationInhibit neutrophil accumulation Impair free radical & mediator releaseImpair free radical & mediator release Inhibit superoxide anion productionInhibit superoxide anion production

DOSES OF COMMONLY USED DRUGSDOSES OF COMMONLY USED DRUGS

DrugDrugInfiltratioInfiltratio

nnConc doseConc dose

PNBPNBConc doseConc dose

SpinalSpinalConc doseConc dose

EpiduralEpiduralConc Conc dosedose

LoxLox

0.5- 0.5- 300/300/

1.0% 1.0% 500500

1-1.5 1-1.5 300/300/

500500

1.5-5 1.5-5 100100

1.5-2 1.5-2 300/300/

500500

BupBup

0.25 0.25 175/175/

225225

0.25- 0.25- 175/175/

0.5 0.5 225225

0.5- 200.5- 20

0.750.750.5- 0.5- 175/175/

0.75 0.75 225225

RopRop0.2- 2000.2- 200

0.50.50.5- 2500.5- 250

1.01.00.5- 15-0.5- 15-

0.75 200.75 200.5- 2000.5- 200

1.01.0

TOXICITY OF LOCAL TOXICITY OF LOCAL ANAESTETICSANAESTETICS

► ALLERGIC REACTIONSALLERGIC REACTIONS:-:-

► <1% of ADR due to LA are due to to allergic <1% of ADR due to LA are due to to allergic reactionsreactions

► More common with esters as compared to amides More common with esters as compared to amides due to formation of PABA related compoundsdue to formation of PABA related compounds

► When using amides, the allergy is mostly to When using amides, the allergy is mostly to methylparaben which is added as a preservativemethylparaben which is added as a preservative

► Cross sensitivity occurs between esters but not Cross sensitivity occurs between esters but not bet agents of different classesbet agents of different classes

► Allergy testing:- intradermal testing by using Allergy testing:- intradermal testing by using preservative free preprationspreservative free preprations

►SYSTEMIC TOXICITYSYSTEMIC TOXICITY:-:-

due to higher plasma conc of the LAdue to higher plasma conc of the LA

►Accidental i.v. injectionAccidental i.v. injection

►Tissue absorption- depends onTissue absorption- depends on

Dose administeredDose administered

Vascularity of the tissueVascularity of the tissue

Use of epinephrineUse of epinephrine

Lipid solubility of the drugLipid solubility of the drug

Acute toxicityAcute toxicity

►Risk of seizure and/or cardiovascular Risk of seizure and/or cardiovascular collapse is increased by:collapse is increased by:

►Cold temperature (slows metabolism)Cold temperature (slows metabolism)►Metabolic or respiratory acidosisMetabolic or respiratory acidosis►HypoxiaHypoxia

Acute ToxicityAcute Toxicity

► With most drugs, CNS toxicity proceeds With most drugs, CNS toxicity proceeds cardiac toxicity, providing a warning of cardiac toxicity, providing a warning of impending disaster.impending disaster.

► Key response: maintain oxygenation and normal COKey response: maintain oxygenation and normal CO22!!

► With bupivacaine, CNS toxicity rapidly With bupivacaine, CNS toxicity rapidly progresses to cardiovascular collapse.progresses to cardiovascular collapse.

► Pregnancy enhances the risk of cardiac Pregnancy enhances the risk of cardiac toxicity.toxicity.

► CNS toxicityCNS toxicity:-:- Toxic conc for lignocaine: 5-10ug/mlToxic conc for lignocaine: 5-10ug/ml

Bupivacaine: 4.5-5.5ug/mlBupivacaine: 4.5-5.5ug/ml

Rate of increase of serum conc is more important Rate of increase of serum conc is more important

than the absolute concentration reachedthan the absolute concentration reached

SymptomsSymptoms- numbness of tongue & circumoral tissues- numbness of tongue & circumoral tissues

restlessness, vertigo, tinnitusrestlessness, vertigo, tinnitus

muscle twitching & tonic clonic seizuresmuscle twitching & tonic clonic seizures

CNS depression with hypotension and apneaCNS depression with hypotension and apnea

coma & cardiac arrest coma & cardiac arrest

Factors reducing seizure threshold: PaCO2, Factors reducing seizure threshold: PaCO2,

hyperkalemia, raised serotonin, mexiletine treatmenthyperkalemia, raised serotonin, mexiletine treatment

►TREATMENTTREATMENT:-:-

HyperventilationHyperventilation

Controlled mechanical ventilation Controlled mechanical ventilation

Midazolam 0.05mg/kg i.v.Midazolam 0.05mg/kg i.v.

Thiopentone 50-100 mg i.v.Thiopentone 50-100 mg i.v.

►CARDIAC TOXICITYCARDIAC TOXICITY:-:- Bupivacaine>Ropivacaine>LignocaineBupivacaine>Ropivacaine>Lignocaine Factors enhancing toxicity of bupivacaine:Factors enhancing toxicity of bupivacaine:

►PregnancyPregnancy►B-blocker, CCB, digoxinB-blocker, CCB, digoxin►Addition of epinephrineAddition of epinephrine►Hypoxia/hypercarbia/acidosisHypoxia/hypercarbia/acidosis

Effects of Bupivacaine Effects of Bupivacaine Isomers on Cardiac Sodium Isomers on Cardiac Sodium

ChannelsChannels

Dextrobupivacaine Dextrobupivacaine Has faster onset of action than Has faster onset of action than

levobupivacainelevobupivacaine Has greater affinity for cardiac Has greater affinity for cardiac

sodium channelssodium channels Has a slower offset timeHas a slower offset time

► Clinical features-Clinical features- Hypotension, chest pain, Hypotension, chest pain,

palpitations, dyspnea, palpitations, dyspnea, diaphoresis, lightheadednessdiaphoresis, lightheadedness

Wide QRS Wide QRS PR intervalPR interval VPCVPC Ventricular tachycardiaVentricular tachycardia Supraventricular tachycardiaSupraventricular tachycardia AV heart blockAV heart block

► Treatment-Treatment- supportive and CPR as under supportive and CPR as under

standard protocolsstandard protocols Bretylium 20mg/kgBretylium 20mg/kg Lipid rescueLipid rescue

► LIPID RESCUELIPID RESCUE:-:- Use of i.v. lipid emulsion to treat severe LA toxicityUse of i.v. lipid emulsion to treat severe LA toxicity

Pioneered by DR. Guy Weinberg in 1998Pioneered by DR. Guy Weinberg in 1998

Mechanism of actionMechanism of action: ‘lipid sink theory’: ‘lipid sink theory’

Exogenous lipid provides an alternate source for Exogenous lipid provides an alternate source for

binding of lipid soluble LAbinding of lipid soluble LA

1.1. Bupivacaine molecules preferentially segregate Bupivacaine molecules preferentially segregate

from plasma to lipid in a 1:12 ratio.from plasma to lipid in a 1:12 ratio.

2.2. It also reacts significantly with tissue bupivacaineIt also reacts significantly with tissue bupivacaine

3.3. Lipid acts as a substrate for cellular energy Lipid acts as a substrate for cellular energy

productionproduction

4.4. May act on NO pathwaysMay act on NO pathways

► DOSAGEDOSAGE:- It is advisable to initiate the lipid :- It is advisable to initiate the lipid infusion once the conventional treatment infusion once the conventional treatment modalities have begun.modalities have begun. i.v. bolus intralipid 20% 1.5 ml/kg over 1 min.i.v. bolus intralipid 20% 1.5 ml/kg over 1 min. i.v. infusion @ 0.25 ml/kg/mini.v. infusion @ 0.25 ml/kg/min Bolus injection at 5 min interval if circulation not Bolus injection at 5 min interval if circulation not

restoredrestored Increase infusion to 0.5 ml/kg/min after 5 min if Increase infusion to 0.5 ml/kg/min after 5 min if

circulation not restoredcirculation not restored

► SIDE EFFECTSSIDE EFFECTS:-:- ThrombophlebitisThrombophlebitis pulmonary hypertensionpulmonary hypertension InfectionInfection warfarin resistancewarfarin resistance Allergic reactionsAllergic reactions ICP after head injury ICP after head injury Fat emboliFat emboli seizures in childrenseizures in children

►METHEMOGLOBINEMIAMETHEMOGLOBINEMIA:-:- m/c with prilocaine, benzocaine & lignocaine m/c with prilocaine, benzocaine & lignocaine

are also responsibleare also responsible

PrilocainePrilocaine Orthotoluidine Orthotoluidine

Hb Oxy Hb Hb Oxy Hb MethemoglobinemiaMethemoglobinemia

►Risk factors: neonates, patients on Risk factors: neonates, patients on oxidising drugsoxidising drugs

►Central cyanosis @ methemoglobin> Central cyanosis @ methemoglobin> 15%15%

MethemoglobinemiaMethemoglobinemia

►10%: clinical anoxia10%: clinical anoxia►60%: stupor, coma, and death. 60%: stupor, coma, and death.

Documented with benzocaine, prilocaineDocumented with benzocaine, prilocaine►Associated with benzocaine and Associated with benzocaine and

prilocaineprilocaine►Treat with methylene blue, 1-2 mg/kg Treat with methylene blue, 1-2 mg/kg

given over 5 minutesgiven over 5 minutes►Faster administration may exacerbate Faster administration may exacerbate

methemoglobinemiamethemoglobinemia

Drug InteractionsDrug Interactions

►Esters are metabolized by Esters are metabolized by pseudocholinesterasepseudocholinesterase

►Compete with succinylcholine for metabolism, Compete with succinylcholine for metabolism, so when given together each lasts longerso when given together each lasts longer

►Metabolism slowed by administration of Metabolism slowed by administration of anticholinesterase (e.g., neostigmine)anticholinesterase (e.g., neostigmine)

Drug InteractionsDrug Interactions

►Local anesthetic toxicities are Local anesthetic toxicities are ADDITIVEADDITIVE

►Divide lidocaine dose / 4 to convert to Divide lidocaine dose / 4 to convert to bupivacaine equivalentsbupivacaine equivalents

►Keep lidocaine / 4 + bupivacaine less than 3 Keep lidocaine / 4 + bupivacaine less than 3 mg/kgmg/kg

ANALGESIA WITH LOCAL ANALGESIA WITH LOCAL ANAESTHETICSANAESTHETICS

Regional anesthesia - UsesRegional anesthesia - Uses

►Provide anesthesia for a surgical Provide anesthesia for a surgical procedure procedure

►Provide analgesia post-operatively or Provide analgesia post-operatively or during labor and deliveryduring labor and delivery

►Diagnosis or therapy for patients with Diagnosis or therapy for patients with chronic pain syndromeschronic pain syndromes

Regional anesthesia - typesRegional anesthesia - types

►TopicalTopical►Local/FieldLocal/Field►Intravenous block (“Bier” block)Intravenous block (“Bier” block)►Peripheral (named) nerve, e.g. Peripheral (named) nerve, e.g.

radial n.radial n.►Plexus - brachial, lumbarPlexus - brachial, lumbar►Central neuraxial - epidural, spinalCentral neuraxial - epidural, spinal

ADJUNCTS TO IMPROVE ADJUNCTS TO IMPROVE ANALGESIA WITH LAANALGESIA WITH LA

-Opiods-Opiods

-Alpha 2 adrenergic receptor agonists -Alpha 2 adrenergic receptor agonists

-Anticholinesteres-Anticholinesteres

-Steroids -Steroids

OPIODSOPIODS

► Analgesic properties are due to spinal and Analgesic properties are due to spinal and supraspinal effect .supraspinal effect .

► No motor block .No motor block .► Synergy with LA .Synergy with LA .► Decrease LA consumption .Decrease LA consumption .► Improve analgesia .Improve analgesia .► Decrease shievering .Decrease shievering .► S/E are nausea , vomitting, respiratory S/E are nausea , vomitting, respiratory

depression.depression.

ADRENERGIC AGONISTSADRENERGIC AGONISTS

►Epinephrine ,clonidine ,dexmedetomidiEpinephrine ,clonidine ,dexmedetomidinene

►Lipophillic compounds .Lipophillic compounds .►Analgesic effect is due to alpha 2 Analgesic effect is due to alpha 2

receptor binding .receptor binding .►Decrease venous uptake of LA and Decrease venous uptake of LA and

increase analgesic and motor block .increase analgesic and motor block .

CLONIDINECLONIDINE

► Show synergy with LA and opiods .Show synergy with LA and opiods .► No respiratory depression and no motor No respiratory depression and no motor

block .block .► It improve analgesia in both spinal and It improve analgesia in both spinal and

epidural but hypotension limits its use .epidural but hypotension limits its use .► Analgesic effect IT Analgesic effect IT > epidural > systemic> epidural > systemic► 0.2-0.3µg/kg prolongs the duraion of sensory 0.2-0.3µg/kg prolongs the duraion of sensory

block by 30%block by 30%► Optimal dose for ambulatory surgery is 30-Optimal dose for ambulatory surgery is 30-

45µg45µg

ANTICHOLINESTERESANTICHOLINESTERES

► NeostigmineNeostigmine► Ach itself has analgesic effect so analgesia is Ach itself has analgesic effect so analgesia is

due to increased Ach conc. as neostigmine due to increased Ach conc. as neostigmine inhibites cholinesterasesinhibites cholinesterases

► No intrathecal useNo intrathecal use► It has modest analgesic actionIt has modest analgesic action► Decrease postop. Analgesic needs Decrease postop. Analgesic needs

particularly effective to spare opiod useparticularly effective to spare opiod use► Bolus dose 4-7Bolus dose 4-7µg/kg and infusion 7µg/ml µg/kg and infusion 7µg/ml

solutionsolution► It increase postop. Analgesia upto 8 hrs with It increase postop. Analgesia upto 8 hrs with

lignocaine.lignocaine.

STEROIDSSTEROIDS

►Steroids have nerve block prolonging Steroids have nerve block prolonging action. action.

►They block the nociceptive impulse They block the nociceptive impulse transmission along unmyelinated c fibrestransmission along unmyelinated c fibres

►Steroid prolongs analgesia significantly Steroid prolongs analgesia significantly when used in nerve blockswhen used in nerve blocks

►They have nerve block prolonging effect They have nerve block prolonging effect accoding to their anti inflammatory accoding to their anti inflammatory potency.potency.