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Overview
Local anesthetics
History Basics and pharmacology Properties and effects Effects and side effects Sequence of onset Different applications Techniques Effects and side effects
(Loco-)Regional anesthesia
History
1996: Ropivacaine 1974: Articaine 1963: Bupivacaine
Local and regional anesthesia
1999: Levobupivacaine
1960: Prilocaine
1952: Chloroprocaine
1957: Mepivacaine 1943: Lidocaine 1898: August Bier, first SA with cocain 1884: Carl Koller, first LA with Cocain
Characteristics
Local anesthetics
Poorly water soluble weak basic amins (pKa 7,5-9) Molecular weight: between 220 and 288 Lipophilic aromatic ring + tertiary hydrophilic amin Link: Ester (-COO-) or Amid (-NHC-) chain
tertiary
06/07 Ch. Szadkowski 4
Characteristics
Local anesthetics
Classification
Local anesthetics
Aminoesters:
Cocaine
Procaine
Aminoamids:
Lidocaine Prilocaine Mepivacaine
Etidocaine
Chloroprocaine
Tetracaine
Characteristics
Local anesthetics
No influence on:
Resting potential and threshold level
Na-channel-block
Local anesthetics Local and regional anesthesia
Diffusion through the nerve cell membrane (nonionised Base B) Na-channel block on the intracelluar side (Kation BH+)
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Arteria Vein
Uptake into circulation depends on: vascularity, vasodilation, LA properties (protein binding, lipid solubility and pKa)
Nerve
Uptake into nerves depends on distance to nerve, LA properties (pKa) and local pH
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Arteria Vein
Elimination into tissue and then circulation depends mostly on LA properties (lipid solubility) Nerve
Distribution: Alpha phase: Rapid uptake into highly perfused organs (brain, lung, liver, kidney, heart) Beta phase: Slower uptake into moderately perfused tissues (muscle, gut)
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Potency and duration of action = Systemic toxicity: toxicity Bupivacaine > Lidocaine Chirality: Bupivacaine >> L-Bupivacaine or Ropivacaine S-Enantiomere with lower cardiac toxicity
Either:
Rapid onset of action Short duration of action Low potency Low toxicity Slow onset of action Long duration of action High(er) potency High(er) toxicity
Or:
Clinical practice:
Mixtures S-Enantiomere
06/07 Ch. Szadkowski
Metabolism
Local anesthetics
Aminoesters:
Quick degradation Hydrolysis, plasma and liver cholinesterase Produces para-aminobenzoic acid (PABA, allergy.)
Aminoamids:
Slower degradation Liver microsomal enzymes Excretion (metabolites and <5% unchanged drug) via kidneys Prilocain (very large doses): - Accumulation of metabolites: risk of methemoglobinemia
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Site of injection:
Onset of action: - Rapid onset of action: spinal application - Slow onset of action: brachial plexus anesthesia - Rapid onset of action: Short distance to nerve(s) Risk for (systemic) toxic reactions: - Higher when high absorption rate:
intercostal > epidural > plexus > infiltration
06/07 Ch. Szadkowski 17
Age:
Old age (> 70 yr): elimination prolonged - 10-20% dose reduction for continuous applications (Level C) Newborns (< 4 months): elimination of amid LA prolonged - 15% dose reduction per kg (Level C)
Renal dysfunction:
Excretion reduced: - 10-20% dose reductions relative to degree of dysfuncion (Level D)
Hepatic dysfunction:
Low liver blood flow or poor liver function: - Higher blood levels of amid local anesthetics - 10-50% dose reduction for repeated or continuous applications
(Level C)
06/07 Ch. Szadkowski 18
Body size:
In very small adults, the dose for blocks requiring large doses (brachial plexus, IVRA) should be reduced (Level D)
Pregnancy:
Hormonally increased sensitivity of the CNS to LA: - Reduced requirements Risk for toxicity : - Reduced protein binding of bupivacaine - Increased cardiac output, perfusion and uptake Anatomic and physiologic changes - 10% dose reduction (Level C)
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Infected tissue:
Low tissue pH: - More ionised kations - Less uncharged base available for penetration Vasodilation: - Uptake into circulating blood Reduced effect of the injected local anesthetic
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Clinical effects
Local anesthetics
Neuroprotection
Systemic toxicity
Local anesthetics
Effects:
Central-nervous Cardio-vascular
Allergic reactions:
Neurotoxicity:
Transient radicular irritation
Myotoxicity:
Local and regional anesthesia
Myonecrosis after intramuscular or trigger point injection Bupivacaine > lidocaine > procaine ( with lipid solubility ) Concomitant steroids or epinephrine: more pronounced Rapid and complete regeneration in most cases
Methemoglobinemia:
Large doses of Prilocaine
Local anesthetics
Cardio-vascular: Early/mild: - Hypertension - Tachycardia Severe: - AV-Dissociation - Bradycardia - Myocardial ischemia - Hypotension - Cardiac arrest
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Plasma concentration
Why:
Prevention of high plasma concentrations of free LA leading to systemic toxic reactions
But:
No scientific base to support the recommendations presented in textbooks and pamphlets of pharmaceutical companies! Max. dose recommendation for lidocaine > 50 yrs old!
Plasma concentrations and time courses after injection of the same (adequate!) dose depend on the injection site!
Grey Area (toxic symptoms possible despite low plasma conc!) Zink W et al. Ansthesist 2003; 52: 1102-23 (Mod. nach Braid u. Scott )
0
06/07 5 Ch. Szadkowski 10 15
20
40
60
min
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IV access secured before injection of the LA Chose least toxic drug suitable Consider block type and patient specific max. dose ranges Start with a typical dose Consider adding a vasoconstrictive adjuvant (epinephrine) Careful aspiration during injection Observe clinical reactions: Talk to the patient and monitor ECG/blood pressure to realize early symptoms of central-nervous and cardiovascular toxicity Stop injection immediately when early symptoms are realized Consider the time course for development of toxic signs (5-10 min)(after correct injection.)
06/07 Ch. Szadkowski 28
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Depends on the rise of LA concentration near the nerves and the length of the fiber exposed to the LA and. (complex explanation theories)
1. Sympathetic nervous system fibers (B fibers: Vasodilation, skin temperature ) 2. Temperature and pain conduction (A and C fibers) 3. Proprioception and touch (A and A fibers) 4. Motor function (A fibers)
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Mucous membranes (nose, mouth/throat, trachea, urethra) Conjunctives Skin (EMLA cream) (absorption through intact skin is unreliable)
Topical anesthesia
Anesthesia
LA can provide effective, but only short acting analgesia Application to:
Intakt skin: - EMLA cream (Lidocaine/Prilocaine base mixture) applied for 45-60 min under occlusive bandage - 1 patch contains 25 mg lidocaine and 25 mg prilocaine - Analgesia of the skin before inserting needles/cannulas Mucous membranes: - Lidocaine 2-4%, Tetracaine 0.25-1%: solution, cream or jelly - Cocaine 4% solution for nose/throat: additional vasoconstriction!
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Infiltration anesthesia
Choice of agent:
Anesthesia
Any commercially available LA can be used Consider neutralisation with sodium bicarbonate
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Injection into a previously exsanguinated and occluded limb Retrograde spread of the distally injected local anesthetic agent Very rapid onset
Possible complications:
LA intoxication when tourniquet is insufficient or released less than 15 - 20 minutes after injection
06/07 Ch. Szadkowski 35
Most local anesthetics can be used Choice depends on intended duration of the block
Dose / concentration:
Lidocaine, Mepivacaine, Prilocaine (1 % solutions) Bupivacaine (0.5 % solution), Ropivacaine (0.75% solution) (10 ) 20 40 ( 50) ml (depending on nerve or plexus type)
Chosen site:
Depends on planned surgical procedure
Injected volume:
30 50 ml
Time to onset:
< 10 min (Lido, Mepi, Prilo) up to 25 min (Bupi, Ropi)
37
Nerve stimulation (single or multiple injections after identifying one or more nerves) Ultrasound Perivascular infiltration (multiple passes around the artery) Transarterial (posterior and anterior injection) (Paresthesia technique)
VB U
38
Very low rate of severe complications Cardiac arrest 0.01%, death 0.005%, seizures 0.08%
Nerve damages:
Permanent deficits: 0 > 5 % (Definition: ??) prospective trials: 0.4% First postoperative day: > 10% Hypo- or paresthesia Minor sensory deficits very frequent: up to 50% But: Transient lesions also after general anesthesia: - Up to 30% after arthroscopic shoulder surgery.
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Spinal anesthesia Sites for puncture Injection site Site of action Dose of LA Onset of action Motor block Complications Only below L2/3 Subarachnoid space (CSF)
Subarachnoid space (nerves and spinal cord) Small Quick Profound Cardiac arrest Postdural puncture syndrome (headache, hearing) (no) Large Slower Moderate LA-intoxication Total spinal anesthesia Epidural hematoma Yes, (thoracic) catheters
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Postop analgesia
06/07 Ch. Szadkowski
Spinal anesthesia
Only use drugs without preservatives! Commonly used: 0.5% Bupivacaine (long action) hyperbaric (with 8% glucose) or plain (isobaric) solution No hyperbaric (=heavy) lidocaine (transient neural symptoms)! Rapid onset (injection close to nerve roots)
Anesthesia Local and regional anesthesia
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Epidural anesthesia
Lido-, Mepiva-, Prilo-, Bupiva-, Ropivacaine Onset 5-15 min (Lido/Mepi/Prilo) to 20-30 min (Bupi/Ropi) Anesthesia: high concentration: 2% Lido/0.5% (L-)Bupi/0.75% Ropi Analgesia postoperative without motor deficit: 0.125-0.25% (L-)Bupi/0.2% Ropi
Anesthesia Local and regional anesthesia
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- Cesarean section Epidural: - Indications as for spinal, +: - Thoracic approach in combination with general anesthesia:
abdominal and thoracic surgery
Absolute
Sepsis (Severe) Coagulopathies Shock, severe hypovolemia Infection at/near puncture site Refusal Certain neurologic diseases Severe aortic valve stenosis Communication problems Elevated intracranial pressure Anatomical abnormalities
Relative
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Cardiovascular system:
Hypotension (related to: extent of sympathetic block, volemia) Bradycardia (blocked sympathetic cardioaccelerator fibers; Young males: more frequent) Both effects more pronounced with spinal than with epidural anesth.
Respiratory system:
Reduced active exhalation with high block level: - Caution in patients with severe COPD!
46
Unopposed parasympathetic activity: - Nausea (associated with high block level) - Increased secretions, relaxed sphincters, bowel constriction Long lasting block of sacral parasympathetic nerves: - Postoperative urinary retention possible
Endocrine-metabolic:
Less perioperative stress-response: - Reduction of: protein catabolism, hyperglycemia, sodium and water retention, fever, tachycardia, increased minute ventilation
Coagulation:
Reduced hypercoagulability, reduced thromboembolic events
06/07 Ch. Szadkowski 47
48
Worst outcome: persistent paraplegia Very low incidence (approx 1 : 100000) Increased risk with:
History of bleeding disorders Coagulation defects oder thrombocytopenia/pathia Not respecting recommended time intervals between puncture or catheter removal and application of the thromboembolic prophylaxis drug Bloody tap / traumatic puncture(s)
Low after spinal anesthesia (thin needles with non-cutting tip) Higher after diagnostic punctures (CSF diagnostic, myelography) and inadvertent dural perforation with epidural needle
Symptoms:
Headache (in upright position) Tinnitus/hearing loss Nausea
Treatment:
Symptoms usually resolve within few days with conservative therapy: Bed rest, analgesics, caffeine, fluids Sometimes epidural homologous blood patch necessary
06/07 Ch. Szadkowski 50
Postoperative Analgesia
Local anesthetics for postoperative analgesia:
Analgesia
(Thoracic) Epidural analgesia Continuous peripheral nerve blocks (Shoulder, Arm, Leg) Continuous wound infiltration (Shoulder, Tram-Flap, .)
But:
Method-specific side effects (similar to regional anesthesia)
06/07 Ch. Szadkowski 51
No difference:
Incidence of postoperative surgical complications
06/07 Ch. Szadkowski 52
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Indication Infiltration Nerve block Neuraxial Infiltration Nerve block Infiltration IVRA Nerve block Infiltration Nerve block Neuraxial Infiltration Nerve block Neuraxial
Concentration (%) (0.5 ) 1 1 ( 1.5) (0.5 ) 1 1 ( 1.5) (0.5 ) 1 0.5 ( 0.75) 12 (0.25 ) 0.5 (0.25 ) 0.5 0,125 (0.5) (0.2 ) 0.75 (0.4 ) 0.75 0.2 (0.5)
Reasonable * doses (mg/kg) 5/7 5/7 7/9 7/9 6/9 6/9 6/9 2/3 2 / 10 in 24h 3 3 / 12 in 24h
Usual onset (min) < 10 < 10 < 10 < 10 < 10 <5 < 10 < 10 15 30 < 10 10 15
Average duration (min) 30-60 / 120 90 / 180 90 45-90 / 180 120 / 240 60-120 Tourniquet 120-180 240 / 360 Up to > 720! 240 240 Up to > 720! 240
Ropivacaine
*:Different informations from differenttextbooks and pharmaceutical companies! without epinephrine with epinephrine 1:200000 mg/kg/24 h for continuous infusion 06/07 Ch. Szadkowski 55
Characteristics : aminoesters
Substance Cocaine pKa 8.5 Onset of action Potency Intermediate (++) Slow Rapid Slow Low (+) Low (+) High (++++) Duration of action Intermediate Relative toxicity Characteristics Vasoconstrition! For topical local anesthesia (nose) Very low Very low Very high For iv local anesthesia
+ = low lipid solubility ++ = intermediate lipid solubility +++/+ = high/very high lipid solubility
06/07 Ch. Szadkowski
Characteristics aminoamids
Substance Lidocaine pK a 7.8 Onset of action Rapid Rapid Rapid Rapid Slow Slow Slow Potency Intermediate (++) Intermediate (++) Intermediate (++) High (++++) High (++++) High (++++) High (++++) Duration of action Intermediate (64) Intermediate (55) Intermediate (77) Long (94) Long (95) Long (94) Long (95) Relative toxicity 1 0.5 1 2 4 < Bupi < Bupi Characteristics Suitable for most applications Lowest toxicity Risk for Met-Hb Similar to lidocain Faster onset of action than bupi Highest toxicity Lower cardiotoxicity Lower cardiotoxicity
+ = low lipid solubility ++ = intermediate lipid solubility , Ch. Szadkowski +++/+06/07 = high/very high lipid solubility