4/26/18 LOCAL ANESTHETICS...LOCAL ANESTHETICS OUTLINE • Terminology, nerve microanatomy, and fiber types • Mechanism of action and pharmacology • Mixtures of local anesthetics

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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