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Anesthesia,Local anesthesia,wangjieUnion Hospital,History,Coca 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 1885 but not introduced into clinical practice until 1899Brachial plexus anesthesia by percutaneous injection through axillary and supraclavicular approaches was developed in the early 20th century.,History,Definition,Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness.,A local anesthetic is a drug that reversibly inhibits the propagation of signals along nerves. Analgesia (loss of pain sensation) Paralysis (loss of muscle power),Local Anesthetics Pharmacology,Classification,StructureAmino esters : procaine tetracaineAmino amides :bupivacaine lidocaine ropivacaineEffective TimeShort term: procaineMiddle: lidocaineLong： bupivacaine tetracaine ropivacaine,(pKa)=pH-logB/BH+ Onset Time,Bases,Ionic positive ion,Pharmacology,SPEED OF ONSET,Weak 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 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,Pharmacology,3. Duration of blockageProtein binding regulate the duration of anaesthetic activityDue to protein binding of LA to protein receptor in the Na channel of nerve mbHighly protein bound will remain for a long time Procain 6% protein boundRopi, bupi, etidocaine 94-96% prot. bound,Pharmacology,Plasma concentration : depends on absorption kinetics HOW WHERE systemic disposition kineticsDistributionElimination metabolism Plasma EZ Liver EZ excretion,Pharmacology,PHARMACOKINETICS,Absorption of LA,Site of injection ( intercostal caudal brachial plexus etc )Dosage (blood level of LA related to total dose of drug rather than spesific volume or concentration of solutionAddition of vasoconstrictor,Metabolism of LA,A. ESTERSRapid hydrolysis by plasma cholinesteraseWater soluble metabolites excreted in the urine (p-aminobenzoic, diethylaminoethanolAbnormal pseudocholinesterase inc risk of toxic side effect CSF lack of esterase enzymeException Cocain - partially metabolized in liver and partially excreted in urine unchanged,Cont.,B. AMIDEEnzymatic degradation in liver by microsomal enzymes (prilocaine lidnocaine mepivacaine bupivacaine and etidocaine )Much slower than ester hydrolysisN-dealkylation, aromatic and amide hydrolysisDecrease hepatic function or hepatic blood flow reduce metabolic rate pred systemic toxicityVery little drug excreted unchanged by kidney,Mechanism of action,Inhibiting sodium influx through sodium-specific ion channels in particular the so-called voltage-gated sodium channelsaction potential cannot arise and signal conduction is thus inhibited,Order of sensory function block,paincoldwarmthtouchdeep pressure motor,Recovery in reverse order,Local anesthetics Side effect,1. Toxicity2. Hypersensitivity/Allergy,Undesired effects!,Toxicity may 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 patients,Local anesthetics Side effect,Clinic presentationNumbness or tingling of the tongue and circumoral areaLightheadedness,anxiety,restlessness, drowsiness and/or complain of tinnitus and visual disturbance,Local anesthetics Side effect,Central nervous system,Excitatory or Depressive At lower concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to generalized convulsions. A profound depression of brain functions occurs at higher concentrations which may lead to coma, respiratory arrest and death.,Cardiovascular system,Bradycardia, but tachyarrhythmia can also occur. With high plasma levels of lidocaine there may be higher-degree atrioventricular block and severe bradycardia, leading to coma and possibly death.,Prevention of toxicityA benzodiazepam premedication is recommendedDo not exceed the maximum safe dose for the particular local anaesthetic used All injections should be given slowly and the dose should be fractionatedAspiration for blood and CSF should always be performedUse of a test dose.Anaesthetic containing 1:200,000 adrenaline is advocated,Local anesthetics Side effect,Management of toxicity,Oxygenation :the airway is maintained and oxygen administered by face-mask,using artificial ventilation if apnoea occurs,Management of toxicity,Control of convulsions:with small increments of either iazepam(5mg)or thiopentone(50mg).But excessive doses should not be given since cardiorespiratory depression maybe happen,Management of toxicity,Circulatory support :hypotension may need to be treated with vasopressors or inotropes (e.G.Ephedrine in 10mg increments).Arrythemia must be managed and if cardiac arrest happened,CPCR should be performed immediately,Hypersensitivity/allergy Allergic reactions are rare, especially with amide local anesthetics. Urticarial rashes are most common, but more serious responses also occur. Mild skin reactions are treated with antihistamines; more serious sequellae require epinephrine.,lidocaine,pKa 7.85Plain aq solution 1, 1.5, 2% pH 5-7Solution with adrenalin pH 3-4.5Ralative potency 2T1/2 adult 1.8 hr, neonate 2hrXtremely stableMax dose : plain 3mg/kg, adrenalin 7mg/kgE.A. of 400mg/70kg blood = 2-4ug/mlToxicity begin 5 ug/mlRelatively quickly absorbed from GITMetab in liver (dealkylation) excreted urineToxic dose lead to death by VF or cardiac arrestSuitable for surface, infiltration,nerve block, caudal, epidural and SA,Bupivacaine,pKa 8.1Plain aq soln .25, .375, .5% pH 4.5-6If with adrenalin pH 3.5-5.5Potency 8Protein binding 95% lipid solubility than lidocaineT1/2 adult 3.5hr, neonate 8.1-14hrAmide link LAProd prolonged anaesthesia with slower onsetAdd adrenalin - toxicity, h/e no change in durationPost op analgesia : IC 7hr, EA 3-4hrEpid/caudal peak plasma 30-45 minLower foetal/maternal ratio cf lidnocaine (! Protein binding)Max dose : plain/with adrenalin 2 mg/kg,Ropivacaine,Chemical analogue of bupivacaineThe molecule is designed to modify the spesific cardiotoxicity associated with bupivacainepKa 8.2 and pH solution 5.5-6.0Equally potent as bupivacaineIts quality of clinical block appear to be very similar in onset, duration and quality that of bupivacaineNo spesific toxicity has been detected,Local anesthesia Methods,Physiology,CSF：120150ml(space2330ml)，pressure lie on one side70170mmh2o，site position200300mmh2o。 Associated with distribution of local anesthetics,Effect Site,Spinal nerve rootSpinal anesthesia: Direct affectEpidural anesthesia: (1)Infiltrating in CSF (2)Spinal nerve,Sequence of nerve block,sympathetic nerveEsthetic nerveMotor nerve,Differential block(Ropivacaine),Lower doses or concentrations may selectively inhibit pain sensation with minimal affect on muscle power. Some techniques of pain therapy, such