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1、AnesthesiaAnesthesiaLocal anesthesia wangjieUnion HospitalHistoryCoca plant leaves in Peru.Cocaine was isolated in 1860 First used as a local anesthetic in 1884.Procaine in 1904.lidocaine in 1943,Bupivacaine in 1957 and prilocaine in 1959.Spinal anesthesia was first used in Spinal anesthesia was fir
2、st used in 1885 but not introduced into 1885 but not introduced into clinical practice until 1899clinical practice until 1899Brachial plexus anesthesia by Brachial plexus anesthesia by percutaneous injection through percutaneous injection through axillary and supraclavicular axillary and supraclavic
3、ular approaches was developed in the approaches was developed in the early 20th century.early 20th century.HistoryDefinitionLocal anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness.A A local anestheticlocal anesthetic is a drug that is a drug t
4、hat reversibly inhibits the propagation of reversibly inhibits the propagation of signals along nerves.signals along nerves.AnalgesiaAnalgesia(loss of pain sensation)(loss of pain sensation)ParalysisParalysis(loss of muscle power)(loss of muscle power)Local Anesthetics Local Anesthetics Pharmacology
5、ClassificationStructureAmino esters:procaine tetracaineAmino esters:procaine tetracaineAmino amides:bupivacaine lidocaine Amino amides:bupivacaine lidocaine ropivacaineropivacaineEffective TimeShort term:procaineShort term:procaineMiddle:lidocaineMiddle:lidocaineLongLong：bupivacaine tetracaine ropiv
6、acainebupivacaine tetracaine ropivacaine1.(pKa)=pH-logB/BH+Onset Time BasesIonic positive ion PharmacologySPEED OF ONSETWeak bases tend to be relatively ionized at high concentration H+The uncharged form diffuse more readily across nerve mb determine the onset of LAOnset of blockage pKaCarbon acidic
7、 lidocaine Quick Effect 2.Lipid solubilityIts effect on onset is poorly understoodhigh lipid solubility inc rate of diff and shorten onset time BUT it also inc solubility in the surrounding tissue Pharmacology3.Duration of blockageProtein binding regulate the duration of Protein binding regulate the
8、 duration of anaesthetic activityanaesthetic activityDue to protein binding of LA to protein Due to protein binding of LA to protein receptor in the Na channel of nerve mbreceptor in the Na channel of nerve mbHighly protein bound will remain for a long Highly protein bound will remain for a long tim
9、e Procain time Procain 6%protein bound 6%protein boundRopi,bupi,etidocaine Ropi,bupi,etidocaine 94-96%prot.94-96%prot.boundbound PharmacologyPlasma concentration :depends onPlasma concentration :depends on absorption kinetics HOW WHERE absorption kinetics HOW WHERE systemic disposition kinetics syst
10、emic disposition kineticsDistributionDistributionEliminationElimination metabolism metabolism Plasma EZ Liver EZPlasma EZ Liver EZ excretion excretion PharmacologyPHARMACOKINETICSAbsorption of LASite of injection (intercostal caudal brachial plexus etc)Dosage (blood level of LA related to total dose
11、 of drug rather than spesific volume or concentration of solutionAddition of vasoconstrictorMetabolism of LAA.ESTERSA.ESTERSRapid hydrolysis by plasma Rapid hydrolysis by plasma cholinesterasecholinesteraseWater soluble metabolites excreted in the Water soluble metabolites excreted in the urine(p-am
12、inobenzoic,urine(p-aminobenzoic,diethylaminoethanoldiethylaminoethanolAbnormal pseudocholinesterase Abnormal pseudocholinesterase inc inc risk of toxic side effectrisk of toxic side effect CSF lack of esterase enzyme CSF lack of esterase enzymeException Cocain -partially metabolized Exception Cocain
13、 -partially metabolized in liver and partially excreted in urine in liver and partially excreted in urine unchangedunchangedCont.B.AMIDEB.AMIDEEnzymatic degradation in liver by Enzymatic degradation in liver by microsomal enzymes (prilocaine microsomal enzymes (prilocaine lidnocaine mepivacaine bupi
14、vacaine lidnocaine mepivacaine bupivacaine and etidocaine)and etidocaine)Much slower than ester hydrolysisMuch slower than ester hydrolysisN-dealkylation,aromatic and amide N-dealkylation,aromatic and amide hydrolysishydrolysisDecrease hepatic function or hepatic Decrease hepatic function or hepatic
15、 blood flow reduce metabolic rate blood flow reduce metabolic rate pred pred systemic toxicitysystemic toxicityVery little drug excreted unchanged by Very little drug excreted unchanged by kidney kidney Mechanism of actionInhibiting sodium influx through sodium-specific ion channels in particular th
16、e so-called voltage-gated sodium channelsaction potential cannot arise and signal conduction is thus inhibitedOrder of sensory function block paincoldwarmthtouchdeep pressure motorRecovery in reverse order Local anesthetics Side effect1.1.Toxicity2.Hypersensitivity/AllergyUndesired effects!Toxicity
17、may occur ifmay occur if The maximum safe dose is exceededTransient high blood levels are achieved by accidental intravenous injectionRapid absorption from an inflamed or vascular areaUse normal dose to weak patientsLocal anesthetics Side effectClinic presentationNumbness or tingling of the tongue a
18、nd circumoral areaLightheadedness,anxiety,restlessness,drowsiness and/or complain of tinnitus and visual disturbanceLocal anesthetics Side effectCentral nervous systemExcitatory or Depressive At lower concentrations,a relatively At lower concentrations,a relatively selective depression of inhibitory
19、 neurons selective depression of inhibitory neurons results in cerebral excitation,which may results in cerebral excitation,which may lead to generalized lead to generalized convulsions.convulsions.A profound depression of brain functions A profound depression of brain functions occurs at higher con
20、centrations which occurs at higher concentrations which may lead to may lead to coma,respiratory arrestcoma,respiratory arrest and and death.death.Cardiovascular systemBradycardia,but tachyarrhythmia can also occur.With high plasma levels of lidocaine there may be higher-degree atrioventricular bloc
21、k and severe bradycardia,leading to coma and possibly death.Prevention of toxicityPrevention of toxicityA benzodiazepam premedication is A benzodiazepam premedication is recommendedrecommendedDo not exceed the maximum safe dose for the Do not exceed the maximum safe dose for the particular local ana
22、esthetic used All injections particular local anaesthetic used All injections should be given slowly and the dose should should be given slowly and the dose should be fractionatedbe fractionatedAspiration for blood and CSF should always be Aspiration for blood and CSF should always be performedperfo
23、rmedUse of a test dose.Anaesthetic containing Use of a test dose.Anaesthetic containing 1:200,000 adrenaline is advocated1:200,000 adrenaline is advocatedLocal anesthetics Side effectManagement of toxicityOxygenation:the airway is maintained and oxygen administered by face-mask,using artificial vent
24、ilation if apnoea occursManagement of toxicityControl of convulsions:with small increments of either iazepam(5mg)or thiopentone(50mg).But excessive doses should not be given since cardiorespiratory depression maybe happenManagement of toxicityCirculatory support:hypotension may need to be treated wi
25、th vasopressors or inotropes(e.G.Ephedrine in 10mg increments).Arrythemia must be managed and if cardiac arrest happened,CPCR should be performed immediatelyHypersensitivity/allergy Allergic reactions are rare,especially with Allergic reactions are rare,especially with amide local anesthetics.Urtica
26、rial rashes amide local anesthetics.Urticarial rashes are most common,but more serious are most common,but more serious responses also occur.Mild skin reactions responses also occur.Mild skin reactions are treated with antihistamines;more are treated with antihistamines;more serious sequellae requir
27、e epinephrine.serious sequellae require epinephrine.lidocainepKa 7.85pKa 7.85Plain aq solution 1,1.5,2%pH 5-7Plain aq solution 1,1.5,2%pH 5-7Solution with adrenalin pH 3-4.5Solution with adrenalin pH 3-4.5Ralative potency 2Ralative potency 2T1/2T1/2 adult 1.8 hr,neonate 2hr adult 1.8 hr,neonate 2hrX
28、tremely stableXtremely stableMax dose:plain 3mg/kg,adrenalin 7mg/kgMax dose:plain 3mg/kg,adrenalin 7mg/kgE.A.of 400mg/70kg blood=2-4ug/mlE.A.of 400mg/70kg blood=2-4ug/mlToxicity begin 5 ug/mlToxicity begin 5 ug/mlRelatively quickly absorbed from GITRelatively quickly absorbed from GITMetab in liver(
29、dealkylation)Metab in liver(dealkylation)excreted urine excreted urineToxic dose lead to death by VF or cardiac arrestToxic dose lead to death by VF or cardiac arrestSuitable for surface,infiltration,nerve block,caudal,Suitable for surface,infiltration,nerve block,caudal,epidural and SAepidural and
30、SABupivacaine pKa 8.1pKa 8.1 Plain aq soln.25,.375,.5%pH 4.5-6Plain aq soln.25,.375,.5%pH 4.5-6 If with adrenalin pH 3.5-5.5If with adrenalin pH 3.5-5.5 Potency 8Potency 8 Protein binding 95%Protein binding 95%lipid solubility than lidocaine lipid solubility than lidocaine T1/2T1/2 adult 3.5hr,neona
31、te 8.1-14hr adult 3.5hr,neonate 8.1-14hr Amide link LAAmide link LA Prod prolonged anaesthesia with slower onsetProd prolonged anaesthesia with slower onset Add adrenalin-Add adrenalin-toxicity,h/e no change in durationtoxicity,h/e no change in duration Post op analgesia:IC 7hr,EA 3-4hrPost op analg
32、esia:IC 7hr,EA 3-4hr Epid/caudal peak plasma 30-45 minEpid/caudal peak plasma 30-45 min Lower foetal/maternal ratio cf lidnocaine(!Protein binding)Lower foetal/maternal ratio cf lidnocaine(!Protein binding)Max dose:plain/with adrenalin 2 mg/kgMax dose:plain/with adrenalin 2 mg/kgRopivacaine Chemical
33、 analogue of bupivacaineChemical analogue of bupivacaineThe molecule is designed to modify the The molecule is designed to modify the spesific cardiotoxicity associated with spesific cardiotoxicity associated with bupivacainebupivacainepKa 8.2 and pH solution 5.5-6.0pKa 8.2 and pH solution 5.5-6.0Eq
34、ually potent as bupivacaineEqually potent as bupivacaineIts quality of clinical block appear to be Its quality of clinical block appear to be very similar in onset,duration and quality very similar in onset,duration and quality that of bupivacainethat of bupivacaineNo spesific toxicity has been dete
35、cted No spesific toxicity has been detected Local anesthesia MethodsLocal anesthesiaSurface anesthesiaLocal infiltration anesthesiaRegional blockNerve blockPhysiologyCSF：120150ml(space2330ml)，pressure lie on one side70170mmh2o，site position200300mmh2o。Associated with distribution of local anesthetic
36、sEffect SiteSpinal nerve rootSpinal nerve rootSpinal anesthesia:Direct affectSpinal anesthesia:Direct affectEpidural anesthesia:Epidural anesthesia:(1)Infiltrating in CSF(1)Infiltrating in CSF (2)Spinal nerve (2)Spinal nerveSequence of nerve blocksympathetic nerveEsthetic nerveMotor nerveDifferentia
37、l block(Ropivacaine)Lower doses or concentrations may Lower doses or concentrations may selectively inhibit pain sensation selectively inhibit pain sensation with minimal affect on muscle with minimal affect on muscle power.Some techniques of pain power.Some techniques of pain therapy,such as walkin
38、g epidurals therapy,such as walking epidurals for labor pain use this effect,for labor pain use this effect,termed differential block.termed differential block.Spinal BlockA more dense blockFast onsetUsed more often for C/SCommon side effect is hypotensionAnesthesia Administration(1)LA Volume(2)Punc
39、ture space(3)Direction(4)Bonus or cont.ComplicationDuring operation:Total spinal anesthesia(Subarachnoid injection)Hypotention Respiratory depression VomitingPostoeration：injury urenary retention Infectionhematoma Indication&contraindicationnHypotention/hypovolaemianCoagulopathynPresence of local tissue sepsisnPatient refusalnAllergy/hypersensitivity to LA/sol.AdditivesEpidural BlockContinuous blockPlaced between dura mater and ligamentum flavumDoes not enter CSFGive bolus-observe for hypotensionChange position frequentlyIf narcotics used can cause resp.Depression