LOCAL ANESTHETICS Alison Clode, DVM, DACVO Port City Veterinary Referral Hospital Portsmouth, New Hampshire New England Equine Medical and Surgical Center Dover, New Hampshire

Overview • Molecular Structure • Mechanism • Side effects • Ophthalmic Uses

Structure • Hydrophobic aromatic ring

•  Intermediate linkage site

• Hydrophilic ionizable amine

Structure • Hydrophobic aromatic

ring •  Establishes lipophilicity

•  Can be altered with substitutions

•  Influences diffusion across nerve cell membrane and metabolism

•  Determines potency and toxicity (binding)

Structure •  Intermediate linkage site

•  Ester (unstable) •  Hydrolyzed by plasma

esterases •  Rapid process

•  Amide (stable) •  Metabolized in the liver •  Slower process

Structure •  Hydrophilic ionizable amine

•  Weak base with pKa 8 to 9 •  Un-ionized fraction (tertiary

amine, lipid-soluble) greater in neutral or basic environment

•  Ionized fraction (quaternary amide, H2O-soluble) increases in acidic environment

•  Determines time to onset based on tissue pH

•  Formulated as hydrochloride salt to increase solubility and stability

Mechanism 1.  Diffusion across cell

membrane (un-ionized form)

Na+ channel

Na+

Un-ionized LA

Neuron

Mechanism 1.  Diffusion across cell

membrane (un-ionized form) 2.  Amine ionizes to ammonium

cation

Na+

Un-ionized LA

Ionized LA

Na+ channel

Neuron

Mechanism 1.  Diffusion across cell

membrane (un-ionized form) 2.  Amine ionizes to ammonium

cation 3.  Ionized form preferentially

binds receptor located on intracellular domain of Na+ channel

Na+

Un-ionized LA

Ionized LA

Na+ channel

Neuron

Mechanism 1.  Diffusion across cell

membrane (un-ionized form) 2.  Amine ionizes to ammonium

cation 3.  Ionized form preferentially

binds receptor located on intracellular domain of Na+ channel

4.  Inhibition of Na+ influx 5.  Inhibition of depolarization à

no action potential

Na+

Un-ionized LA

Ionized LA

Na+ channel

Neuron

More details… •  Binding affinity of aromatic ring to inner aspect of Na+ channel

determined by protein binding •  Increased protein binding à greater binding affinity à increased

potency

•  Binding is increased with greater activity of receptors, which occurs when neurons are rapidly firing •  Increased binding à increased anesthetic effect

•  Small diameter neurons are more sensitive than larger diameter neurons

•  Duration of activity is determined by contact time

Contact time influenced by: •  Lipid solubility (aromatic ring)

•  Determines diffusion into neuron •  Correlates with binding affinity to sodium channels •  Increased lipophilicity à increased binding affinity

•  Local environment •  Alkaline environment increases un-ionized (lipophilic, tertiary) proportion •  Acidic environment (i.e., infection) increases ionized (hydrophilic,

quaternary) proportion •  Increased hydrophilic proportion correlates with increased time to onset

because of decreased diffusion into neuron

•  Concentration •  LA with greater lipid solubility are formulated in lower concentrations

•  Rate of removal by diffusion and circulation

Methods to increase contact time: •  Addition of vasoconstrictor

•  Epinephrine 1:100,000 to 1:200,000 •  Decreases clearance from site of action •  Decreases systemic absorption/toxicity •  Provides hemostasis •  May induce local tissue necrosis

•  Addition of buffer •  1:10 bicarbonate to lidocaine •  1:20 bicarbonate to bupivicaine •  Increases local pH to increase un-ionized (diffusable) form of drug

More details… CHARACTERISTIC DETERMINES MECHANISM

Lipid solubility (aromatic ring)

Potency Greater lipid solubility à greater diffusion into neuron

Plasma protein binding (aromatic ring)

Duration of action Greater plasma protein binding à greater affinity for receptor proteins à prolonged presence at site of action

Ester versus amide (intermediate linkage)

Metabolism Esterases versus hepatic metabolism

pKa (terminal amine) Time to onset HIGHER pH à greater lipid portion à greater diffusion à faster onset

Adapted from Becker DE and Reed KL, Anes Prog, 2006

Comparison Agent Concentration Duration to

onset (min) Duration of action (hr)

Lidocaine

1% 1 ½ - 1

Lidocaine

2% 1 ½ - 1

Lidocaine + epinephrine

1%

1 2 – 6

Mepivacaine 2% 1 2 – 3

Bupivacaine

0.25% 5 2 – 4

Bupivacaine + epinephrine

0.25% 5 3 – 7

Topical LA •  Efficacy = ability to suppress

corneal sensitivity

•  Maximum effective concentration = concentration above which no increase in efficacy occurs

•  Optimum effective concentration = concentration associated with least adverse effects

** Effects NOT additive **

Topical LA – Side effects •  Corneal toxicity:

1.  Localized or diffuse desquamation à superficial punctate keratitis

2.  Diffuse necrotizing epithelial keratitis

3.  Severe infiltrative keratitis, often in a ring formation

4.  Persistent epithelial defects 5.  Descemet’s membrane folding

Yagci A, et al., Cornea 2011

Topical LA – Side effects •  Mechanisms of toxicity:

•  Disrupt microvilli à altered tear film adherence

•  Impede epithelial migration •  Direct effect on keratocytes and

endothelial cells •  Ag-Ab deposition from epithelial

cell breakdown •  Oxidative stress

•  Decreased blink •  Decreased reflex tearing

Topical LA – Side effects •  Ocular irritation:

•  Conjunctival hyperemia, chemosis, lacrimation, blepharedema, pruritus

•  Rapid onset

•  Treat with compresses, topical anti-inflammatories

•  Can generally use a different agent without problems

Topical LA – Side effects •  IOP alterations?

•  Topical anesthetics suspected to alter endothelial Na+/K+ pump à increased stromal hydration à increased central corneal thickness (CCT)

•  Altered CCT may complicate diagnosis of glaucoma •  Thin corneas à underestimation of actual IOP •  Thick corneas à overestimation of actual IOP

Topical LA – Side effects •  Systemic toxicity:

•  No serious systemic reactions reported with appropriate use of topical anesthetics

•  Systemic absorption problematic with: •  Large doses (inappropriate administration) •  Rapid absorption (i.e., conjunctival hyperemia) •  Unusually slow drug detoxification •  Unusually slow drug elimination

Topical LA – Side effects •  Systemic hypersensitivity:

•  LA are too small to be immunogenic on their own

•  Hapten + carrier may à pseudoallergic reaction •  Suggestive of hypersensitivity but without known immune basis

•  Anaphylactoid reaction = pseudoallergic reaction mimicking severity of IgE-mediated reaction •  Vasodilator release occurs, but via non-IgE-mediated mechanism •  Angioneurotic edema, hives, bronchospasm, hypotension

•  Rare

Topical LA – Side effects •  CNS = stimulation followed by

depression

•  Cardiovascular = hypertension and tachycardia followed by hypotension and weak to absent pulse

•  Respiratory = failure

Becker DE and Reed KL, Anes Prog, 2006

Suggested maximum topical dosages Anesthetic agent Dosage for humans Cocaine 4% 20 mg

(approximately 5 drops in each eye)

Tetracaine 0.5% 5 mg (approximately 7 drops in each eye)

Proparacaine 0.5% 10 mg (approximately 14 drops in each eye)

Than TP and Bartlett JD. In Clinical Ocular Pharmacology, 2008.

Extrapolated*** maximum topical dosages Anesthetic agent

Dosage for humans Dosage for dogs***

Tetracaine 0.5% 5 mg (approximately 7 drops in each eye)

1.5 mg (approximately 2 drops in each eye)

Proparacaine 0.5% 10 mg (approximately 14 drops in each eye)

3.3 mg (approximately 5 drops in each eye)

*** Extrapolations based on supposing 90 kg person and 30 kg dog

*** Extrapolations are my own and should not be quoted as fact, just used for the sake of argument

Topical LA – Contraindications •  Previous anaphylactoid reaction

•  Anticholinesterase medication (neostigmine, pyridostigmine)

•  Perforating ocular injury

•  Endothelial damage •  Preservatives

•  Culture collection

Specific topical LA

Cocaine •  Not commercially available as an

ophthalmic solution

•  Local anesthetic effects: •  1% to 4% •  1 drop of 2%

•  Complete corneal anesthesia within 5 to 10 minutes

•  Duration 20 minutes •  Incomplete anesthesia 1 to 2

hours

•  Adrenergic effects: •  Diagnosis of Horner’s (10%) •  Vasoconstriction

Cocaine – Side effects •  Corneal epithelial toxicity

•  Systemic toxicity •  20 mg = 10 drops of 4%

solution (humans) •  Excitement, restlessness,

headache, rapid irregular pulse, nausea, vomiting, mydriasis

•  Addiction

Cocaine – Contraindications •  Systemic hypertension

•  Medication with adrenergic agonists

•  Medication with anticholinesterases

•  Angle-closure glaucoma

Tetracaine •  0.5% - 1% solution •  Poor efficacy for scleral

anesthesia

•  Greater inhibition of bacterial growth than proparacaine

•  High topical toxicity •  High systemic toxicity

Tetracaine in horses – efficacy

Duration of corneal anaesthesia following multiple doses andtwo concentrations of tetracaine hydrochloride eyedrops onthe normal equine corneaS. J. MONCLIN*, F. FARNIR† and M. GRAUWELS

Departments of Clinical Sciences, Ophthalmology and †Animal Production, Faculty of Veterinary Medicine, Liège University, Belgium.

Keywords: horse; cornea; tetracaine hydrochloride; corneal sensitivity; Cochet-Bonnet aesthesiometer

Summary

Reasons for performing study: There is a clinical impressionthat tetracaine hydrochloride (THCl) eyedrops is a suitabletopical anaesthetic in horses.

Objective: To determine the duration of corneal anaesthesiafollowing instillation of multiple doses and 2 concentrations ofTHCl in 10 healthy horses.

Methods: The corneal touch threshold (CTT) wasdetermined, in both eyes, before (basal CTT) and afterapplication of one drop of 0.5%THCl, 2 drops at a 1 mininterval of 0.5%THCl or one drop of 1%THCl. CTT wasmeasured in mm every 5 min until complete recovery of thebasal CTT. Treatments were separated by an interval of atleast one week.

Results: Corneal sensitivity was significantly reduced frombaseline values for 30, 60 and 50 min after application of onedrop of 0.5%THCl, 2 drops of 0.5%THCl and one drop of1%THCl, respectively. Mean maximal anaesthetic effects,corresponding to a CTT of 0 mm, lasted 5.5, 16 and 15.25 minand maximal anaesthetic effect was present in 55, 90and 80% of eyes, 5 min after application of one drop of0.5%THCl, 2 drops of 0.5%THCl and one drop of 1%THCl,respectively.

Conclusions: The application of a second drop or the useof more concentrated eyedrops significantly increasesduration of both anaesthesia and maximal anaesthetic effect.

Potential relevance: Duration of corneal anaesthesia followingtetracaine instillation was established enabling a better usewhen performing diagnostic and therapeutic procedures.Comparison of tetracaine with other ocular anaestheticsneeds to be published in the future.

Introduction

Although topical anaesthetics have been used for a long timein veterinary ophthalmology, there are only few studies on theireffects in domestic animals. For years, duration of action of thesedrugs has been based on empirical clinical experience, arbitrarydecisions in medicine and veterinary medicine (Formston 1964).Herring et al. (2005) showed that application of one or 2 drops of

0.5% proparacaine on the eyes of clinically normal dogs resultedin a significant corneal anaesthetic effect lasting 45 and 55 min,respectively; with the maximal effect lasting approximately 15and 25 min, respectively. Binder and Herring (2006) reported that50 ml of 0.5% proparacaine induced a maximal anaesthetic effect(MAE) lasting 5 min while the decrease of corneal sensitivitylasted 25 min in cats. The duration of corneal anaesthesia with0.2 ml of ophthalmic 0.5% proparacaine hydrochloride wasfound to be 25 min in horses (Kalf et al. 2008). In the same studyperformed in horses, the corneal touch threshold (CTT) neverdiminished to 0 despite MAE happening within 5 min followingdrug instillation. Duration of corneal anaesthesia induced bythese drugs has also been studied in rabbits and man (Polse et al.1978; Weiss and Goren 1991; Liu et al. 1993; Bartfield et al.1994; Shafi and Koay 1998). Bartfield et al. (1994) comparedeffects of tetracaine and proparacaine in man. They concludedthat anaesthesia induced by tetracaine was slightly shorter: 9.4 vs.10.7 min.

Pain, local irritation and chemosis have been reported with theuse of tetracaine (Koch and Rubin 1969; Shafi and Koay 1998).However, Monclin et al. (2008) did not observe any side effectsassociated with the instillation of 0.5 or 1% tetracainehydrochloride (THCl) in horses and concluded this molecule wasvery well tolerated in horses.

The Cochet-Bonnet aesthesiometer is a metallic cylindricaldevice that allows a nylon filament of known diameter to slide inand out the cylinder. The filament has an adjustable length from5–60 mm and has to be applied perpendicularly to the cornea. Theexposed filament length determines the pressure exerted on thecornea. The corneal touch threshold is determined as the pressure atwhich the majority of touch stimuli cause a blink response (Ollivieret al. 2007). Standardised CTT is reported in mg/0.0113 mm2,the aesthesiometer allowing the application of a pressure of11–200 mg/0.0113 mm2. Therefore, the CTT and cornealsensitivity are inversely proportional: the higher the CTT, the lowerthe corneal sensitivity. To simplify the results, CTT are oftenreported in mm of length of filament (Brooks et al. 2000; Kapset al. 2003; Herring et al. 2005; Binder and Herring 2006; Kalfet al. 2008).

Corneal aesthesiometry is a well defined and feasibleprocedure to realise in the horse. Corneal sensitivity was measured

*Corresponding author. Present address: 6 Ryder Court, Rainhill Prescot, Merseyside L35 4PW, UK. Email: smonclin@hotmail.com[Paper received for publication 16.01.10; Accepted 19.02.10]

EQUINE VETERINARY JOURNAL 69Equine vet. J. (2011) 43 (1) 69-73doi: 10.1111/j.2042-3306.2010.00118.x

© 2010 EVJ Ltd

0.5% 1 drop

0.5% 2 drops

1% 1 drop

Maximal effect in 5 min

55% of horses

90% of horses

80% of horses

Duration of maximal effect

5 min 16 min 15 min

Total duration of effect

30 min 60 min 50 min

Tetracaine in horses – efficacy Time of MAE

Degree of MAE

Duration of MAE

0.5% proparacaine

10 min 0.5 cm 20 min

0.5% tetracaine

10 min 0.25 cm 20 min

0.5% tetracaine (viscous)

10 min 0 cm 30 min

Tetracaine in horses – side effects •  Normal horses

•  0.5% or 1% once

•  Clinical exam •  Time 0, 2.5, 5 min

•  TBUT •  Time 0, 2.5, 5 min

•  0.5% à significantly faster TBUT at 5 min

•  1% à significantly faster TBUT at 2.5 and 5 min

Determination of tear break-up time reference values andocular tolerance of tetracaine hydrochloride eyedops inhealthy horsesS. J. MONCLIN*, F. FARNIR† and M. GRAUWELS

Departments of Clinical Sciences, Ophthalmology and †Animal Production, Faculty of Veterinary Medicine, Liège University, Belgium.

Keywords: horse; cornea; tetracaine hydrochloride; tear break-up time; tolerance

Summary

Reasons for performing study: Tetracaine hydrochloride (THCl)has been reported to cause irritation in dogs. In man, sometopical anaesthetics have been shown to disrupt the tear film.Tear break-up time (TBUT) is a useful test allowing anassessment of the quality of the precorneal tear film. Only oneTBUT value has been reported in horses with no informationon the technique used.

Objectives: To provide a method for performing the TBUT inhorses and to report any side effects of a single application ofTHCl in clinically normal horses, particularly on the stabilityof the tear film.

Methods: In Study 1, one drop of 0.5 or 1% THCl was appliedto one eye of 20 horses divided in 2 groups. Treated eyes wereassessed for the development of side effects 2.5 and 5 min aftertreatment. In Study 2, the TBUT was measured in both eyesof 2 groups of 10 horses, before and 2.5 and 5 min after,instillation of one drop of either 0.5 or 1% THCl.

Results: No animals developed any ocular side effect afterinstillation. Basal TBUT was 8.3 ! 1.3 s. TBUT decreasedfrom baseline 5 and 2.5 min after application of one drop of0.5% THCl and one drop of 1% THCl, respectively.

Conclusions: A technique to measure the TBUT in healthyhorses is described and normal range values that could beused as a reference were obtained.

Potential relevance: THCl is well tolerated in horses but lowersthe TBUT.

Introduction

Topical ophthalmic anaesthetics are useful drugs to facilitate bothdiagnostic and therapeutic procedures. Although they have longbeen used in veterinary ophthalmology, there are only a few studieson their ocular tolerance and anaesthetic effects in animals. In aletter to editor, Koch and Rubin (1969) reported hyperaemia,chemosis and protrusion of the third eyelid after the instillation oftetracaine hydrochloride 0.5% (0.5% THCl) in 2 dogs. Whencomparing the results of 2 studies on corneal anaesthesia in horses,tetracaine seems to be more effective than proparacaine as it

increases the chance of a maximal anaesthetic effect (Kalf et al.2008; Monclin et al. 2008).

In man, topical proparacaine has been reported to destabilisethe preocular tear film (PTF) whereas topical oxybuprocaine hadno effect on PTF stability (Lemp and Hamill 1973; Mengher et al.1986). To the authors’ knowledge, there is no report on the effect oftetracaine on tear film stability in man. This is the first study onocular tolerance and effects on the PTF of tetracaine hydrochlorideeyedrops in horses.

The tear film break-up time (TBUT) is a noninvasive oculardiagnostic test that allows an assessment of the quality of thePTF by observing its stability over the corneal surface. Itcorresponds to the time required for the ocular surface to losecohesive surface wetting after each blink. The average TBUTsreported are 16.7 ! 4.5, 19.7 ! 5 and >13 s in cats (Cullen et al.2005), sedated dogs (Moore 1990) and horses (Harling 1988),respectively. However, no information on the technique, numberof eyes tested nor statistical analysis is available in the studyperformed on horses.

The objectives of this study were: to report in clinically normalhorses any possible side effects of a single topical application oftetracaine used at 2 different concentrations (Study 1); to determinein healthy horses the baseline value of the TBUT (Study 2); and toassess the effect of tetracaine hydrochloride eyedrops at 2concentrations on the stability of the PTF by measurement of theTBUT (Study 2).

Materials and methods

Forty healthy Saddlebred horses belonging to the PhysiologyDepartment of the Veterinary School of Liège or to the PoliceDepartment of Brussels, Belgium, were involved in these 2 studies.None of these horses were under local or systemic therapy and allunderwent a complete ophthalmic examination to ensure theabsence of ocular disease. All tests were performed by the sameinvestigators in a closed barn, in the usual quiet environment ofthe animals. The same person handled the horses with minimalrestraint and without sedation. Studies were conducted inaccordance with the rules of the Ethical Committee of theUniversity of Liège, Belgium.

*Corresponding author. Present address: 6 Ryder Court, Rainhill Prescot, Merseyside L35 4PW, UK. Email: smonclin@hotmail.com[Paper received for publication 16.01.10; Accepted 19.02.10]

© 2010 EVJ Ltd

74 EQUINE VETERINARY JOURNALEquine vet. J. (2011) 43 (1) 74-77

doi: 10.1111/j.2042-3306.2010.00119.x

Proparacaine •  0.5% solution •  Comparison with tetracaine:

•  Less corneal/conjunctival penetration

•  Less pain on administration •  Less inhibition of bacterial growth

•  Refrigerate after opening •  Discard if discolored

Proparacaine in dogs – efficacy Single drop

Two drops 1 min apart

Onset < 1 min < 1 min

Duration of MAE

15 min 25 min

Total duration

45 min 55 min

Proparacaine in cats – efficacy Single drop

Onset < 1 min

Duration of maximal effect

5 min

Total duration of effect

25 min

Proparacaine in horses – efficacy 0.2 ml once

Onset < 1 min

Time point of maximal effect

5 min

Total duration of effect

25 min

Benoxinate (oxybuprocaine) •  0.25% + sodium fluorescein •  0.35% + disodium fluorexon

•  HMW hydrogel that does not stain contact lenses

•  Bactericidal •  Primary use = applanation

tonometry

•  Significant increase in corneal thickness

•  Low risk of local hypersensitivity reaction

Benoxinate (oxybuprocaine) in dogs – efficacy

Single drop 0.4%

Single drop 1% tetracaine

Onset < 1 min < 1 min

Duration of MAE

30 min 30 min

Total duration

55 min 55 min

Benoxinate (oxybuprocaine) in cats – efficacy

Single drop 0.4%

Onset 1 min Duration of MAE

5 min

Total duration

45 min

Injectable Local Anesthetics

Intracameral local anesthetics •  Preservative-free

•  Lidocaine (1% or 2%) •  Ropivacaine (1%) •  Levobupivacaine (0.75%)

•  Indicated for intraocular surgery •  Analgesia •  Mydriasis

Intracameral LA – analgesia •  Reduces intraoperative pain •  Increases intraoperative patient

compliance

•  No alteration in short-term (1 month) or long-term (6 year): •  BCVA •  EC loss •  Corneal thickness •  PCO prevalence or severity

Intracameral LA – mydriasis •  Relaxation of iris sphincter à

mydriasis

•  Comparison between topical mydriatics and intracameral lidocaine •  Greater dilation with lidocaine •  No need for intraoperative mydriatic

Intracameral LA – toxicity •  In vitro lidocaine

•  Transient decrease in cell viability, inhibition of cell proliferation, and DNA degradation

•  In vivo in rabbits •  Potential EC microstructural

alterations

•  Caution should be exercised, particularly in cases with corneal pathology

Intracameral LA – analgesia in dogs •  Lidocaine à

•  Significantly reduced isoflurane requirements

•  Significantly longer time to post-operative treatment failure (rescue analgesia) •  5 hours versus 1.5 hours

Intracameral LA – mydriasis in dogs •  In vivo

•  1% lidocaine, 2% lidocaine, BSS •  0.1 ml, 0.2 ml, 0.3 ml

•  All à pupil diameter > 10 mm •  Most rapid onset with 0.3 ml 2% •  Most delayed onset with 0.1 ml 1% •  Longest duration with 0.3 ml 2% •  Shortest duration with 0.1 ml 1%

Intracameral LA – toxicity in dogs •  In vivo evaluation •  1% lidocaine versus 2%

lidocaine versus BSS

•  No changes: •  EC density •  EC morphology •  Corneal edema •  Corneal thickness •  IOP

Retrobulbar LA •  Block CN II, CN III, CN IV, CN

VI, ophthalmic and maxillary of CN V

•  Indications: •  Analgesia •  Akinesia •  Mydriasis

Parness G, et al., CEACCP 2005

Retrobulbar LA •  Retrobulbar (intraconal)

•  “More risky” •  More rapid onset •  Smaller volumes

•  Peribulbar (extraconal) •  “Less risky” •  Slower onset •  Larger volumes

•  Possible complications •  Retrobulbar hemorrhage •  Ptosis •  Globe perforation •  Chemosis

Parness G, et al., CEACCP 2005

Retrobulbar LA •  Review of clinical trials in human ophthalmology comparing RB and PB

•  No significant difference in pain control •  No significant difference in akinesia rates •  Greater (but not significant) need for repeat injections with PB technique •  No significant difference in effect with or without sedation

•  Greater occurrence of chemosis with PB •  Retrobulbar hemorrhage in 1 patient in RB group •  Persistent ptosis in ~1% in each group

* Alhassan MB, et al., The Cochrane Collaboration, 2011

Retrobulbar LA in horses •  U/S-guidance with CT evaluation of contrast spread:

•  Better caudal spread of contrast with intraconal placement

•  Extraconal may result in caudal contrast spread

•  GA with or without RB block: •  Without RB block à significant decrease in HR

•  Globe traction •  Pressure on orbital fat pad

•  Increased incidence of bradyarrhythmias

Retrobulbar LA in cattle •  Comparison of modified RB and

Peterson blocks

•  Retrobulbar: •  D, V, M, L quadrants •  10 mL volume each spot

•  Peterson: •  Notch formed by supraorbital process +

zygomatic arch + coronoid process •  12 mL total volume

•  Broader spread with RB •  Consistent infiltration of oculomotor

bundle with RB

Retrobulbar LA in dogs •  ITP technique

•  Mild exophthalmos •  Increase in PD •  No alteration in IOP •  Central positioning of globe

•  No adverse effects post-anesthesia •  STT •  Corneal sensitivity •  Ocular motility

•  Less consistent mydriasis than subtenon’s injection, but effective pain control

Retrobulbar LA in dogs – analgesia •  Decreased need for rescue analgesia following

enucleation

•  Possible improvement in pain control with injection versus LA-soaked hemostatic sponge

•  Possible improvement in pain control with pre-operative injection versus intra-operative splash block

Myrna K et al., JAVMA 2010 Ploog et al., JAVMA 2014 Chow D et al., VO 2015

Retrobulbar LA in cats •  Distribution study •  RB (1 ml dorsomedial) •  PB1 (4 ml dorsomedial) •  PB2 (2 ml dorsomedial + 2 ml

ventrolateral)

•  RB à intraconal (5/7), extraconal (4/7) •  PB1 à intraconal (7/7), extraconal (7/7) •  PB2 à intraconal (6/6), extraconal (6/6)

•  Estimated clinical success: •  RB 71% •  PB1 86% •  PB2 67%

Systemic infusion of local anesthetics •  Pre-emptive therapy for painful procedures •  Limited evaluation specific to ocular surgeries

•  In dogs prior to cataract surgery •  Bolus + CRI of lidocaine versus morphine versus saline control •  Routine phacoemulsification (research dogs) •  Saline: 100% treatment failure within 15 min post-op •  Morphine: 50% treatment failure within 1 hour post-op •  Lidocaine: 50% treatment failure within 1.75 hours post-op

Summary – local anesthetics •  Structure – hydrophobic aromatic ring, ester or amide linkage,

hydrophilic ionizable amine •  Mechanism of action – penetrate neuron, bind and block Na+

channel, inhibit depolarization •  Local and systemic toxicities

•  Local anesthetics are necessary, but must be used judiciously, particularly when considering the size and absorptive capacity of some of our veterinary patients***

•  Topical application – relative efficacy versus topical side effects versus systemic absorption

•  Intracameral injection – relative efficacy versus intraocular toxicity •  Retrobulbar injection – relative efficacy versus injection risks •  Systemic infusion – relative efficacy versus alternatives

Questions?