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LOCAL ANAESTHETICS are the drugs that produce reversible conduction blockade of nerve impulses along central and peripheral pathways after regional anaesthesia.
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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.