4/26/18 local anesthetics...local anesthetics outline • terminology, nerve microanatomy, and fiber...
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4/26/18
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M I C H E L E ( M I K E ) B A R L E T T A , D V M , M S , P H D , D A C VA A A S S I S T A N T P R O F E S S O R A N E S T H E S I O L O G Y C O L L E G E O F V E T E R I N A R Y M E D I C I N E V E T E R I N A R Y T E A C H I N G H O S P I T A L U N I V E R S I T Y O F G E O R G I A
LOCAL ANESTHETICS
OUTLINE
• Terminology, nerve microanatomy, and fiber types
• Mechanism of action and pharmacology • Mixtures of local anesthetics • Adjuvants
• Potential adverse effects
• Local techniques
TERMINOLOGY
• Topical or surface anesthesia • Topical application (e.g. EMLA, lidocaine patches)
• Local or infiltration anesthesia • Injection in surgical field (e.g. injection or infusion catheters)
• Regional or nerve (plexus) block anesthesia • Injection in vicinity of a peripheral nerve
• Neuraxial anesthesia • Injection around spinal cord or in subarachnoid space
• Intravenous regional anesthesia • IV Injection in extremities after exsanguination and
placement of a tourniquet
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NERVE MICROANATOMY
L Campoy & MR Read “Small Animal Regional Anesthesia and Analgesia”, Wiley-Blackwell, 2013 p 12
NERVE FIBERS
Fiber Diameter (μm) Myelin Conduction
velocity (m/s) Innervation Function Nerve block onset
Aα 6-20 +++ 75-120 Aff: spindle proprioceptors Eff: skeletal muscles
Motor, reflex +
Aβ 5-12 +++ 30-70 Aff: cutaneous mechanoceptors
Touch, pressure ++
Aγ 3-6 ++ 12-35 Eff: muscle spindle Muscle tone +++
Aδ 1-5 ++ 5-30 Aff: pain and temperature (T)
Fast pain, touch, T ++++
B < 3 + 3-15 Eff: sympathetic Autonomic +++++
C 0.2-1.5 − 0.5-2 Aff: pain and temperature (T)
Slow pain, T
++++
L Campoy & MR Read “Small Animal Regional Anesthesia and Analgesia”, Wiley-Blackwell, 2013 p 29
NERVE FIBERS
Fiber Diameter (μm) Myelin Conduction
velocity (m/s) Innervation Function Nerve block onset
Aα 6-20 +++ 75-120 Aff: spindle proprioceptors Eff: skeletal muscles
Motor, reflex +
Aβ 5-12 +++ 30-70 Aff: cutaneous mechanoceptors
Touch, pressure ++
Aγ 3-6 ++ 12-35 Eff: muscle spindle Muscle tone +++
Aδ 1-5 ++ 5-30 Aff: pain and temperature (T)
Fast pain, touch, T ++++
B < 3 + 3-15 Eff: sympathetic Autonomic +++++
C 0.2-1.5 − 0.5-2 Aff: pain and temperature (T)
Slow pain, T
++++
L Campoy & MR Read “Small Animal Regional Anesthesia and Analgesia”, Wiley-Blackwell, 2013 p 29
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CLASSES
lipophilic benzene
ring
hydrophilic tertiary amine
amide bond
ester bond
http://en.wikipedia.org/wiki/File:Procaine.svg http://en.wikipedia.org/wiki/File:Lidocaine.svg
Aminoamides lidocaine
Aminoesters procaine
CLASSES
Aminoamides
• Lidocaine • Etidocaine • Prilocaine • Mepivacaine • Bupivacaine • Levobupivacaine • Ropivacaine
Aminoesters
• Procaine • Benzocaine • Chlorprocaine • Tetracaine • Cocaine
CLASSES
Aminoamides
• Lidocaine • Etidocaine • Prilocaine • Mepivacaine • Bupivacaine • Levobupivacaine • Ropivacaine
Aminoesters
• Procaine • Benzocaine • Chlorprocaine • Tetracaine • Cocaine
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OUTLINE
• Terminology, nerve microanatomy, and fiber types
• Mechanism of action and pharmacology • Mixtures of local anesthetics • Adjuvants
• Potential adverse effects
• Local techniques
MECHANISM OF ACTION
WJ Tranquilli, JC Thurmon, KA Grimm “Lumb & Jones’ Veterinary Anesthesia and Analgesia” 4th ed., Blackwell Publishing, 2007 p 406
http://images.medicinenet.com/images/slideshow/multiple-sclerosis- s4-illustration-of-nerve-fibers-and-myelin-attack-in-ms.jpg
http://vectorblog.org/wp-content/uploads/2013/06/
MECHANISM OF ACTION
WJ Tranquilli, JC Thurmon, KA Grimm “Lumb & Jones’ Veterinary Anesthesia and Analgesia” 4th ed., Blackwell Publishing, 2007 p 397
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MECHANISM OF ACTION
Katzung BG, Masters SB, Trevor AJ “Basic & Clinical Pharmacology” 11th ed http://basic-clinical-pharmacology.net/chapter%2014_%20agents%20used%20in%20cardiac%20arrhythmias.htm
Rested-closed Activated-open Inactivated-closed
m = activation gate h = inactivation gate
Local anesthetics
Frequency-dependent
blockade
Extracellular
Intracellular
m m m m m m
+
+
Na+ + Na
+ + Na+ +
h
h h
Local anesthetics block the Na+ channel in this configuration
PHARMACOLOGY
Agent % ionized
Lipid solubility
% protein binding Onset Duration
(min) Max dose (mg/kg)
Bupivacaine Levobupivacaine 83 30 95 slow 180-480 2 mg/kg
Lidocaine 76 3.6 65 fast 60-120 6 mg/kg
Mepivacaine 61 2 75 fast 90-180 6 mg/kg
Ropivacaine 83 14 94 slow 300-480 2 mg/kg
• More ionized = slow onset • More lipid soluble = more potent (also longer onset and duration) • More protein bound = longer duration
MIXTURES OF LOCAL ANESTHETICS
• Few data available
• Decreased concentration of both drugs • Potential slower onset of the rapid one and shorter duration
of the long-lasting one
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EVIDENCE
• Galindo A, Witcher T. Mixtures of local anesthetics: bupivacaine-chloroprocaine. Anesth Analg. 1980 Sep;59(9):683-5
• rat sciatic nerve • 1 leg saline the other:
a. 0.5% bupivacaine b. 2% chloroprocaine (fast onset, short duration: 30-60 min) c. 50/50 mixture of 0.5% bupivacaine and 2% chloroprocaine
• Results • characteristics c = b • changing pH from 3.6 to 5.56 −> c = a
EVIDENCE
• Ribotsky BM1, Berkowitz KD, Montague JR. Local anesthetics. Is there an advantage to mixing solutions? J Am Podiatr Med Assoc. 1996 Oct;86(10):487-91
• 12 human subject, both feet • 1 foot saline the other:
a. 1% lidocaine b. 0.25% bupivacaine c. 50/50 mixture of 1% lidocaine and 0.25% bupivacaine
• Results • duration b > a = c • no advantages in mixing
EVIDENCE
• Cuvillon P et al. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study. Anesth Analg. 2009 Feb;108(2):641-9
• 82 human patients • Sciatic and femoral blocks with:
a. 0.5% bupivacaine b. 50/50 mixture of 0.5% bupivacaine and 2% lidocaine c. 0.75% ropivacaine d. 50/50 mixture of 0.5% ropivacaine and 2% lidocaine
• Results • Lidocaine shortened the onset but decreased the duration
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ADJUVANTS
• Epinephrine (1:200,000 or 5μg/ml) • Add 0.1 ml of epinephrine 1:1,000 (1 mg/ml) to 20 ml of local
anesthetic • Vasoconstriction and decreases bleeding • Decreases systemic absorption • Lowers pH and increases onset of action
• Bicarbonate • Decreases onset and prolongs duration (ion trapping) • Decreases pain on injection • Lidocaine and mepivacaine −> add 1mEq NaHCO3/10ml • Bupivacaine and etidocaine −>NO, they precipitate
ADJUVANTS
• Opioids • Buprenorphine commonly used
• long duration • local anesthetic-like effect (block of Na+ channels)
• Studies in people but no in vet med • Sciatic nerve block and minor oral surgeries • What I do:
• buprenorphine 5-10 μg/kg + bupivacaine
• Alpha2-agonists • Dexmedetomidine used in rats and people (palatine n. block) • Decreases onset and increases duration • What I do:
• dexmedetomidine 0.5-1 μg/kg + bupivacaine
OUTLINE
• Terminology, nerve microanatomy, and fiber types
• Mechanism of action and pharmacology • Mixtures of local anesthetics • Adjuvants
• Potential adverse effects
• Local techniques
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TOXICITY
• Cardiovascular depression
• Respiratory arrest • Coma • Convulsions • Unconsciousness • Muscular twitching • Visual and auditory
disturbances • Lightheadedness • Numbness of the tongue
• Neurotoxicity – lidocaine
• Cardiovascular toxicity – Bupivacaine
• Methemoglobinemia (cats) – benzocaine, prilocaine, procaine, and
lidocaine (less often)
pla
sma
co
nc
en
tra
tion
TOXICITY
• Prevent • Calculate total dose
Recommended doses for blocks
Agent Dog Cat
Bupivacaine Up to 2 mg/kg Up to 1 mg/kg
Lidocaine Up to 6 mg/kg Up to 3 mg/kg
Mepivacaine Up to 6 mg/kg Up to 3 mg/kg
Lumb & Jones’ “Veterinary Anesthesia and Analgesia” 4th ed., Blackwell Publishing, 2007 p 994
TOXICITY
• Treatment depends on signs • IV fluids • Vasopressors/inotropes • Anticholinergics • CPR • Lipid emulsion 20%
• 4 ml/kg bolus, followed by 0.5 ml/kg/min for 10 minutes
• Methylene blue 1% (if methemoglobinemia) • 4 mg/kg in dogs and 1-2 mg/kg in cats
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OUTLINE
• Terminology, nerve microanatomy, and fiber types
• Mechanism of action and pharmacology • Mixtures of local anesthetics • Adjuvants
• Potential adverse effects
• Local techniques
INTERCOSTAL BLOCK
Lumb & Jones’ “Veterinary Anesthesia and Analgesia” fourth ed. P 568
BRACHIAL PLEXUS BLOCK
Lumb & Jones’ “Veterinary Anesthesia and Analgesia” fourth ed. P 572
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INTRAVENOUS REGIONAL ANESTHESIA (BIER BLOCK)
August Bier
http-//upload.wikimedia.org/wikipedia/commons/1/18/August_Bier
Tranquilli, Grimm, and Lamont “Pain Management for the Small Animal Practitioner”
INTRAVENOUS REGIONAL ANESTHESIA (BIER BLOCK)
EPIDURAL INJECTION
Lumb & Jones’ “Veterinary Anesthesia and Analgesia” fourth ed. P 575
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EPIDURAL INJECTION
EPIDURAL INJECTION
MAXILLARY BLOCK SUBZYGOMATIC OR TRANSCUTANEOUS APPROACH
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MAXILLARY BLOCK MAXILLARY TUBEROSITY OR INTRAORAL APPROACH
MAXILLARY BLOCK
• It desensitizes
• ipsilateral upper lip • skin of the nose • mucosa of soft and hard palate • maxilla including the teeth and associated soft tissues
• Infraorbital approach • higher risk of damaging neurovascular structures
QUESTIONS
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