Anaesthisea PDF

Local and regional anesthesia
Vorkurs 1 Pathophysiologische Grundlagen der Chirurgie fr das Basisexamen
Lausanne, 13. Juni 2007 Christine Szadkowski

Leiterin Ansthesie Hirslanden Klinik Am Rosenberg 9410 Heiden
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
06/07 Ch. Szadkowski
History
1996: Ropivacaine 1974: Articaine 1963: Bupivacaine
1999: Levobupivacaine
1960: Prilocaine
1952: Chloroprocaine
1957: Mepivacaine 1943: Lidocaine 1898: August Bier, first SA with cocain 1884: Carl Koller, first LA with Cocain
1930: Tetracaine 1905: Procaine 1884: Cocain
1850: Local anesthesia

06/07 Ch. Szadkowski 3
Characteristics
Local anesthetics
Remember: pKa of all LA is higher than pH!
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
Characteristics
Local anesthetics
Henderson-Hasselbalch equation pH = pKa + log B / BH+
Two forms exist simultaneously:

Ionised kation (BH+) Non ionised base (B)
Relation between the two forms depends on:

pKa of the local anesthetic drug Tissue (and solution) pH
The lower the difference between pKa and pH (less basic LA), the more non ionised molecules (base). More non ionised molecules = quicker onset of action
Both forms necessary for the action:

Neutral base: - Penetrates the membrane of the nerve cell Kation: Active form - Blocks Na-channels (intracellular)
Classification
Local anesthetics
Aminoesters:
Cocaine
Procaine
Aminoamids:
Lidocaine Prilocaine Mepivacaine
Etidocaine
Chloroprocaine
Tetracaine
Bupivacaine Ropivacaine Levobupivacaine
Characteristics
Local anesthetics
All local anesthetics:

Block generation and propagation of electrical impulses in excitable tissues - Peripheral nerves, spinal cord, CNS, cardiac nerves - Autonomic, sensible and motor nerve fibres Reversible block Inhibition of sodium-influx (by blocking Na-channels)
Structure differencies result in specific properties and effects:

pKa Lipid solubility Protein binding Chirality
Properties determine effects
Time to onset Duration of action Potency Toxicity

7
Influence on action potential

Local anesthetics
No influence on:
Resting potential and threshold level
Local anesthetic and Na-channels:

Reduced/blocked sodium entry Slower depolarisation Threshold level not reached Action potential not propagated
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+)
Lipophily and water solubility??

Local anesthetics
How can a lipophilic base get dissolved in aqueous solution?

Addition of hydrochloric acid (HCl): - Soluble hydrochloride salts
Low pH (6-7 without epinephrine; 4 -5 with epinephrine) Solution contains much more kations (BH+) than uncharged neutral base (B)
Neutralisation needed to obtain the active agent - After or before injection:

Effect of tissue HCO3- or addition of sodium bicarbonate Result: more uncharged base (B) (necessary for penetration of the nerve membrane!)
10
What happens after the injection?

Local anesthetics
Inadvertant
intravascular injection: toxicity!!!
Arteria Vein
Uptake into circulation depends on: vascularity, vasodilation, LA properties (protein binding, lipid solubility and pKa)
Injected local anesthetic agent
Nerve
Uptake into nerves depends on distance to nerve, LA properties (pKa) and local pH
11
What happens after the injection?

Local anesthetics
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)
12
Drug specific properties and effects

Local anesthetics
What determines time to onset of action?

pKa (= ionization ) = time to onset
Only drug related properties and effects listed here!
pKa: onset Lidocaine: 7.8 quick Bupivacaine: 8.1 intermediate
What determines potency?

Lipid solubility = potency
lip. sol. potency Lidocaine: 46 Intermediate Bupivacaine: 390 High
What determines duration of action?

Protein binding and lipid solubility = duration of action
prot. bind. duration Lidocaine: 64 intermediate Bupivacaine: 95 long
13
Drug specific properties and effects

Local anesthetics
What determines systemic toxicity?
Only drug related properties and effects listed here!
Potency and duration of action = Systemic toxicity: toxicity Bupivacaine > Lidocaine Chirality: Bupivacaine >> L-Bupivacaine or Ropivacaine S-Enantiomere with lower cardiac toxicity
What determines neuro- and myotoxicity?

Lipid solubility = more muscle cell necrosis Etiology neurotoxicity??
low pH? Preservative? High concentration?
Tissue toxicity: Bupivacaine > Ropivacaine > Lidocaine
(Still?) no ideal local anesthetic available

Local anesthetics
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
Lidocain (Xylocain) Mepivacain (Scandicain) Prilocain (Xylonest)
Or:
Bupivacain (Carbostesin) Ropivacain (Naropin) (Tetracain)
Clinical practice:
Mixtures S-Enantiomere
Prilo-, Mepi- or Lidocaine + Bupi- or Ropivacain L-Bupivacain, Ropivacain

15
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
16
Influencing factors: dose and site of injection

Local anesthetics
Dose (Volume and/or concentration):

Time to onset Duration of action More profound motor block But: risk of toxicity
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
Influencing factors: patient-related

Local anesthetics
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)

Local anesthetics
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)
19

Local anesthetics
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
20
Influencing factors: type of solution

Local anesthetics
Alkalinization (pH with sodium bicarbonate):

Uncharged base, diffusion rate through nerve membrane - Time to onset And: Injection is less painful ! (higher pH) But: Duration of action Recipe: 9 ml LA (lidocaine, mepivacaine) +1 ml NaBic 8.4%
Adjuvant (Epinephrine 1 : 200000 (5 g/ml))

Vasoconstriction: Intravascular uptake - Duration of action 30-50% only in combination with short acting LA (Lido-, Prilo-, Mepivacaine!) - Toxicity (all LA) Contraindication for epinephrine: Recipe: Local anesthesia around 20 ml LA + 0.1 mg Epinephrine
end arteries (finger, ear, penis)!
21
Clinical effects
Local anesthetics
Antinociceptive Some other reported effects:

Antiarrhythmic Better bowel function postop (thoracic epidural analgesia) Antithrombotic Reduction of inflammation processes (lung, gut, systemic, and) Antibacterial Influence on wound healing?
- Negative in vitro versus no or positive effect in vivo
Neuroprotection
Partly controversial results, only few clinical studies

Mechanisms of these other effects not yet fully understood Ongoing research
Systemic toxicity
Local anesthetics
High plasma concentration of free unbound LA:

Inadvertent intravascular injection Excessive dose Excessive resorption Reduced elimination
Effects:
Central-nervous Cardio-vascular
Long acting and potent substances: dangerous!

Bupivacaine (Fast in, slow out) - Cardiac resuscitation extremely difficult!
Other side effects

Local anesthetics
Allergic reactions:
Ester LA, preservatives, para-aminobenzoic acid)

Clinically relevant muscle dysfunction mostly occurs after retro-/peribulbar local anesthesia
Neurotoxicity:
Transient radicular irritation
Myotoxicity:
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
Side effects of adjuvants:

Epinephrine, Clonidine, Steroids
Symptoms of systemic toxicity

Central-nervous: Excitation: - Circumoral numbness - Tongue paresthesia - Dizziness - Blurred vision - Tinnitus - Restlessness - Confusion/Agitation - Muscular twitchings - Seizures tonic clonic Depression: - Loss of conscience - Respiratory arrest - Death
Local anesthetics
Cardio-vascular: Early/mild: - Hypertension - Tachycardia Severe: - AV-Dissociation - Bradycardia - Myocardial ischemia - Hypotension - Cardiac arrest
25
Plasma concentration
Concept of maximum recommended doses

Local anesthetics
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!
Recommendations do not take into account:

Patient-related factors (age, organ dysfunction, pregnancy) Site of injection Individual amount of uptake into circulation
(Vascularity, vasodilation, inadvertent intravascular injection)
Duration and rate of application: Single shot injection or continuous infusion

Plasma concentration: site of injection and time

Local anesthetics
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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Systemic toxicity: Prevention

Local anesthetics Local and regional anesthesia
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.)
Systemic toxicity: Treatment

Local anesthetics
Midazolam 2-5 mg Thiopental 50-150 mg Propofol 50-100 mg
Stop injection immediately Treat:

Give oxygen, (hyper-)ventilate (mask or airway device) Stop cerebral excitation (Benzodiazepines, Barbiturates, Propofol) Correct hypotension and arrhythmias (crystalloids, vasopressors, antiarrhythmic drugs) Cardiopulmonary resuscitation for cardiac arrest / VF
Avoid / treat aggravating factors:

Hypoxia and acidosis (respiratory and metabolic)
Ephedrin 5-10 mg Epinephrine 10-100 g
29
Local anesthetics: Caution!

Local anesthetics
Known allergy (to any component of the formula!):

Cutaneous, cardiovascular and respiratory consequences Avoid substances that caused allergic reactions
Injection into highly vascularised tissues:

Risk of toxicity Aspiration. Observation of the patient.
Patient-related factors with metabolism or sensitivity :

Risk of toxicity Consider dose reduction
Infections/inflammations at injection site:

Reduced effect (low tissue pH...)
Bleeding disorders and anticoagulation therapy:

Hematoma
Regional anesthesia: Sequence of onset

Sequence of onset of anesthesia
Anesthesia
Depends on the rise of LA concentration near the nerves and the length of the fiber exposed to the LA and. (complex explanation theories)
Clinically observed sequence:

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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Examples of clinical applications

Topical anesthesia:
Anesthesia
Mucous membranes (nose, mouth/throat, trachea, urethra) Conjunctives Skin (EMLA cream) (absorption through intact skin is unreliable)
Infiltration anesthesia (unmyelinated nerve endings):

Wound margins, joints and trigger points Tumescent local anesthesia
Intravenous regional anesthesia Conduction (perineural) anesthesia:

Peripheral nerve blocks (eg. brachial plexus) Central (neuraxial) blocks: Spinal, epidural, nerve roots Sympathetic nerve blocks
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!
33
Infiltration anesthesia
Choice of agent:
Anesthesia
Any commercially available LA can be used Consider neutralisation with sodium bicarbonate
Dose (volume and concentration):

Ideal volume depends on extent of the area to be anesthetized - Suitable volumes: (5- )10 50 ml More volume with lower concentrations: - Lidocaine still effective as dilute as 0.05 to 0.1% (tumescent local anesthesia)
Onset of action and duration:

Onset is quick Prolonged duration of action with added epinephrine
34
Intravenous regional anesthesia

How does it work?
Anesthesia
Injection into a previously exsanguinated and occluded limb Retrograde spread of the distally injected local anesthetic agent Very rapid onset
For arm/leg procedures < 1hour Can be performed with:

Prilocaine, Chloroprocaine, Lidocaine (0.5% solution, 40-60 ml)
Possible complications:
LA intoxication when tourniquet is insufficient or released less than 15 - 20 minutes after injection
Peripheral nerve blocks

Choice of agent:
Anesthesia
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)
Onset of action and duration:

Onset is rapid for Lido/Mepi/Prilocaine and slow for Bupi/Ropi Time to onset and duration with considerable variations
(depending on distance of LA deposit to nerves)
Epinephrine prolongs duration of Lido/Mepi/Prilocaine, but is less effective with Bupivacaine

Brachial plexus block

Block possible at different sites:
Anesthesia
Interscalene (Supraclavicular) Infraclavicular Axillary
Nerve roots from: (C4-)C5-C8(-Th1)
Interscalene Infraclavicular Axillary
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
Axillary brachial plexus block: Techniques

Blocking the nerves located around the axillary artery:
Anesthesia
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
Peripheral nerve blocks: Complications

Few outcome studies:
Anesthesia
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.
39
Central (neuraxial) anesthesia: Anatomy

Anesthesia Local and regional anesthesia
Endpoint for spinal anesthesia: cerebrospinal fluid
Endpoint for epidural anesthesia: Loss of resistance
40
Spinal and epidural: Important differences

Anesthesia
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)
Epidural anesthesia Sacral, lumbar, thoracic and cervical Epidural space
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
41
Postop analgesia
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)
42
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
43
Spinal and epidural anesthesia

Main indications:
Anesthesia
Spinal: - Surgery below the umbilicus

lower abdomen lower extremities transurethral and vaginal procedures
- Cesarean section Epidural: - Indications as for spinal, +: - Thoracic approach in combination with general anesthesia:
abdominal and thoracic surgery
- Obstetric analgesia - Treatment of acute and chronic pain

Spinal and epidural anesthesia

Contraindications:
Anesthesia
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
45
Spinal and epidural anesthesia: Effects

Main effects:
Anesthesia
Anesthesia and analgesia
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
Spinal and epidural anesthesia: Effects

Gastrointestinal and urogenital:
Anesthesia
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
Neuraxial blocks: Complications

Other sources: Paraplegia after epidural anesthesia~ 1/100000
48
Spinal epidural hematoma

Anesthesia
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)
Diagnosis and treatment:

Lower extremity numbness/weakness, bladder dysfunction Early detection (MRI) and surgical decompression (within 68 h!) : - Higher chance for complete neurologic recovery!
Postdural puncture syndrome

Incidence after dural puncture:
Anesthesia
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
Postoperative Analgesia
Local anesthetics for postoperative analgesia:
Analgesia
(Thoracic) Epidural analgesia Continuous peripheral nerve blocks (Shoulder, Arm, Leg) Continuous wound infiltration (Shoulder, Tram-Flap, .)
Advantages compared with systemic opioid-based analgesia:

Decreased postoperative pain Better analgesic effect Reduced opioid-related side-effects (Nausea/Vomiting, Pruritus, Sedation) Also suitable for some outpatients (elastomere pumps)
But:
Method-specific side effects (similar to regional anesthesia)
Postoperative epidural analgesia

Type of solution:
Anesthesia
LA (low concentration) and opioid (and epinephrine)
Advantages compared with systemic opioid analgesia:

Better analgesic quality Less sedation, less postoperative fatigue Higher Health related quality of life Earlier mobilization Better respiratory function, better exercise capacity Better bowel function, earlier oral nutrition Earlier ready for discharge (not done, other factors.)
No difference:
Incidence of postoperative surgical complications
Postoperativa epidural analgesia

Anesthesia
Potential problems and complications:

Local anesthetics: - Hypotension - Motor block - Urinary retention Opioids: - Respiratory depression - Urinary retention - Pruritus - Nausea
Catheter: - Epidural hematoma - Infection
53
Tabellen mit Zusammenstellungen
54
Amid local anesthetics for different procedures

Drug Lidocaine Mepivacaine Local and regional anesthesia Prilocaine Bupivacaine
(Levo- and racemic)
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
Procaine Chloroprocaine Tetracaine
8.9 8.7 8.5
Short (5.8) Short Long (76)
+ = low lipid solubility ++ = intermediate lipid solubility +++/+ = high/very high lipid solubility
Protein binding: Number in ( )

56
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
Prilocaine 7.9 Mepivacaine

7.6 7.7 8.1 8.1
Etidocaine Bupivacaine Ropivacaine
Levobupi- 8.1 vacaine
+ = low lipid solubility ++ = intermediate lipid solubility , Ch. Szadkowski +++/+06/07 = high/very high lipid solubility
Protein binding: Relative toxicity compared to lidocaine Number in ( ) 57

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Local and regional anesthesia

Vorkurs 1 Pathophysiologische Grundlagen der Chirurgie fr das Basisexamen

Lausanne, 13. Juni 2007 Christine Szadkowski

Local and regional anesthesia

06/07 Ch. Szadkowski

1930: Tetracaine 1905: Procaine 1884: Cocain

1850: Local anesthesia

Remember: pKa of all LA is higher than pH!

Local and regional anesthesia

Henderson-Hasselbalch equation pH = pKa + log B / BH+

Two forms exist simultaneously:

Relation between the two forms depends on:

Local and regional anesthesia

Both forms necessary for the action:

Local and regional anesthesia

Bupivacaine Ropivacaine Levobupivacaine

06/07 Ch. Szadkowski

All local anesthetics:

Local and regional anesthesia

Structure differencies result in specific properties and effects:

Properties determine effects

Time to onset Duration of action Potency Toxicity

Influence on action potential

Local anesthetic and Na-channels:

Local and regional anesthesia

06/07 Ch. Szadkowski

06/07 Ch. Szadkowski

Lipophily and water solubility??

How can a lipophilic base get dissolved in aqueous solution?

Local and regional anesthesia

Neutralisation needed to obtain the active agent - After or before injection:

06/07 Ch. Szadkowski

What happens after the injection?

intravascular injection: toxicity!!!

Local and regional anesthesia

Injected local anesthetic agent

06/07 Ch. Szadkowski

What happens after the injection?

Local and regional anesthesia

06/07 Ch. Szadkowski

Drug specific properties and effects

What determines time to onset of action?

Only drug related properties and effects listed here!

pKa: onset Lidocaine: 7.8 quick Bupivacaine: 8.1 intermediate

What determines potency?

Lipid solubility = potency

lip. sol. potency Lidocaine: 46 Intermediate Bupivacaine: 390 High

What determines duration of action?

06/07 Ch. Szadkowski

Drug specific properties and effects

What determines systemic toxicity?

Only drug related properties and effects listed here!

Local and regional anesthesia

What determines neuro- and myotoxicity?

Tissue toxicity: Bupivacaine > Ropivacaine > Lidocaine

(Still?) no ideal local anesthetic available

Lidocain (Xylocain) Mepivacain (Scandicain) Prilocain (Xylonest)

Local and regional anesthesia

Bupivacain (Carbostesin) Ropivacain (Naropin) (Tetracain)

Prilo-, Mepi- or Lidocaine + Bupi- or Ropivacain L-Bupivacain, Ropivacain

Local and regional anesthesia

06/07 Ch. Szadkowski

Influencing factors: dose and site of injection