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Pain Management via Locoregional (Epidural) Approach Beyond Sodium Channel

Blockers

Lyon Yonghoon Lee, DVM, PhD, DACVA

College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, USA

Several features of local anesthesia render it particularly useful in veterinary practice. Although

many surgical procedures can be carried out satisfactorily under local anesthesia alone, sedation or

general anesthesia may become necessary depending on the species, temperament and health of the

animal, and on the magnitude of the procedure. Preemptive local anesthesia in animals undergoing

general anesthesia will reduce the amount of general anesthetic, thus minimizing the cardiopulmonary

depression that may accompany and also leading to quicker recovery. It may also provide a useful pain

relief even beyond the full recovery from general anesthesia. Local anesthesia can be largelysubdivided into surface (or topical) anesthesia, infiltration anesthesia, intrasynovial anesthesia, and

epidural anesthesia in accordance with specific nerve or anatomic sites of its application.

Local anesthesia has been most commonly carried out utilizing sodium channel blockers such as

lidocaine and bupivacaine. However, more recently, other classes of analgesics including opioids, alpha

2 agonists, NMDA antagonists, and NSAIDs are increasingly being utilized particularly for epidural

anesthesia for cranial laparotomies or hindlimb orthopedic procedures in small animals. These

non-conventional local analgesics proved to provide equally effective or superior analgesia, and

extended duration with reduced unwanted side effects either in itself or in combination with sodium

channel blocker. The current presentation will focus on various analgesics advocated to be useful in

epidural anesthesia in small animals.

ANATOMYAND TECHNIQUESOF EPIDURAL ANESTHESIAIN DOGSAND CATS

The epidural injection site in dogs and cats is located at the lumbosacral junction between the seventh

lumbar (L-7) and the first sacral vertebra (S-1). In dogs the spinal cord terminates at around 6/7th

lumbar vertebrae. Anterior epidural anesthesia may therefore be safely and easily induced at the

lumbosacral junction. The spinal cord is supported, protected, and stabilized by vertebral column,

ligaments and meninges. The epidural space is located immediately below the ligamentum flavum

separating the dura mater from the vertebral periosteum, the lining of the spinal canal. To locate the

site, identify the iliac prominences on either side, and take an imaginary line between them crossing

the dorsal spinous process of the last lumbar segment. The site for the needle insertion is immediately

caudal to this, in the midline. Restrain laterally or in sternal recumbency (personal preference). To

perform epidural anesthesia, the injection must be made only into the epidural space, between the

ligamentum flavum and dura mater. Epidural injection should be differentiated from spinal (or

intrathecal) injection, in which the anesthetic is injected into the subarachnoid space, between the

arachnoid membrane and the pia mater (this is also where the myelogram is performed in the disc

problem dogs). Anesthetic agents injected into the subarachnoid space (spinal injection) produce true

spinal anesthesia because of the lack of protection provided by the dura mater and arachnoid

meninges. Consequently, the volume of the anesthetic solution must be reduced by one third.

Hypotension can be a major complication. This procedure should not be carried out unless there is an

intravenous line in place so fluids or anti-hypotensives can be given promptly. The epidural space is

identified by advancing the needle from an area of high resistance (ligamentum flavum) to an area of

low resistance (epidural space). This is usually accomplished using the "hanging drop" or the "lack of

resistance" technique during injection. Dangers of spinal and epidural block include hypotension,

hindlimb motor paralysis, infection, and irritation.

PHARMACOLOGICAL CHOICES

Sodium Channel Blockers (SCB)

Sodium channel blockers interfere nerve conduction by inhibiting influx of sodium ions through

ion-selective sodium channels in nerve membrane leading to impairment of the generation of action

potential. This in turn provides blockade both for sensory input and motor activity of the innervated

area resulting in local anesthesia.

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Lidocaine and bupivacaine are the two most commonly employed in veterinary medicine belonging to

this class of drug. Lidocaine possesses reasonably rapid onset of action, with good spreading

properties, providing about one to two hour duration of epidural analgesia. Bupivacaine has a

prolonged duration of action; up to eight hours. It is therefore preferred over lidocaine for epidural

anesthesia particularly in prolonged surgery and for benefit of postoperative analgesia.

Several precautions must be taken into account in the use of SCB. Accidental intravenous injection of

this drug is the most common cause of adverse reaction associated with local anesthe tic

administration. In severe cases it can cause cardiac arrest. When the plasma concentration of SCB is

excessive, sufficient cardiac sodium channels become blocked so that conduction and automaticity

become adversely depressed. One should always draw back on syringe to check not in vein before

injecting SCB local anesthetic. As a very rough guide, the toxic dose of lidocaine would be 8 mg/kg

(much lower in the cat, 2mg/kg) and 4 mg/kg of bupivacaine. (NB, in very small animals such as

domestic cats, small dogs, goat kids, birds and small mammals this amount can be easily exceeded

using solutions of standard concentration, so dilute it carefully and use with caution).

For epidural use, much lower dose is prescribed; a dose of 12 mg/kg of lidocaine or 0.51 mg/kg of

bupivacaine. Undesirable signs of overdose are initial sedation, followed with increasing dosage by

twitching, convulsions, coma and death. A common acceptable side effect is hindlimb paralysis for

short period after recovery. Many clinical research and observation report that analgesics of different

classes such as opioids, SCB, and alpha 2 agonists provide extended duration of epidural analgesia,

with significantly improved motor function than in animals treated only with sodium channel blockers.Additionally, combination of these agents with SCB prolongs the analgesia that is achieved with each

class of drug alone.

Opioids

The most popular pharmacological choice except SCB in epidural anesthesia is opioids in veterinary

use. The drugs bind to opioid receptors in the CNS which usually have inhibitory effects on neurons

resulting in spinal analgesia. Examples of most commonly used drugs in this class for epidural

anesthesia are morphine and hydromorphone. Major advantages are opioids outlast analgesia either

alone or in combination with SCB, and keep the patient ambulatory due to sparing motor effect.

Since realizing opioid's potential as effective analgesic via epidural route in 80's, these have gained a

wider acceptance in epidural anesthesia both in human and veterinary medicine, and indeed the author

would prefer opioids over SCB in epidural anesthesia in small animals. However, Troncy reported ifmorphine (0.2 mg/kg) is combined with bupivacaine (1 mg/kg) epidurally, it results in superior and

prolonged analgesia than morphine (0.2 mg/kg) alone in dogs. As previously mentioned, synergistic

effect for opioids and SCB is well established meriting multimodal approach in performing epidural

anesthesia.

Alpha 2 Agonists

Alpha 2 agonists's mechanism of action is mainly through its agonist activity at presynaptic alpha-2

adrenergic receptors that results in decrease in release of norepinephrine from adrenergic nerve

terminals in CNS and periphery. This causes sedation, decreased sympathetic activity, analgesia, and

hypotension. Main clinical uses are to decrease anxiety, provide chemical restraint with relatively

dependable sedation, potentiate effects of other drugs and provide analgesia. The duration of action

via systemic administration is dose dependent, and typically lasts 10 to 30 minutes of sedation and

restraint for xylazine and 60 to 90 minutes for medetomidine. One good advantage of this class of

drugs is its ability to enable pharmacological reversal with alpha-2 adrenergic antagonists:

atipamezole, yohimbine, and tolazoline.

Although alpha 2 agonists such as xylazine and detomidine has been favored for epidural analgesia

in large animals including horses because of less ataxia and extended duration of effect than lidocaine,

similar consideration is of less concern in small animals. It has been demonstrated that epidurally

administered xylazine (0.25 mg/kg) provides analgesia in dogs greater than four hours.1

It is

suggested that combination of alpha 2 agonists with lidocaine or bupivacaine will provide synergistic

effect with superior and longer lasting analgesia than when a sodium channel blocker is used alone.

NMDA Antagonists

The examples of NMDA (n-methyl-d-aspartate) antagonist in veterinary use a re ketamine andtiletamine. The mechanism of action is through its NMDA (n-methyl-d-aspartate) - glutamate

antagonistic effect which inhibits neurotransmission, and causes a variety of pharmacological effects

including analgesia. Since tiletamine is only available as combined agent with zolazepam, it is ketamine

that would be more practical for epidural administration. Results on ketamine's use for epidural

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anesthesia are conflicting. Rao et alreported 0.4 mg/kg of ketamine epidurally provided 90 minutes of

analgesia, while 2 mg/kg of epidural ketamine was of little use in treating experimentally induced

synovitis in dogs. Currently, better alternatives are available in providing epidural analgesia in small

animals.

SUMMARY

Epidural anesthesia has become a more common practice in small animals in recent years. It could

provide additional intraoperative analgesia to reduce inhalant requirement during general anesthesia,

thereby minimizing the cardiopulmonary depression that may accompany and also leading to quicker

recovery. It may also provide a useful pain relief even beyond the full recovery from general

anesthesia. Drugs of choice for epidural anesthesia have expanded beyond traditional sodium channel

blockers that include opioids, alpha 2 agonists, and NMDA antagonists. It is suggested utilization of

these agents in epidural anesthesia in multimodal approach offers several advantages such as reduced

adverse side effects, prolonged duration and superior analgesia. Further studies are warranted to

provide more information regarding epidural use of different classes of analgesics in combination,

particularly in dosages and duration of effect.

References

1. Rector E, Kramer S, Kietzmann M, Hart S, Nolte I. Evaluation of the antinociceptive effect of systemic and

epidurally applied xylazine in general anesthesia with isoflurane in dogs and the effect of atipamezole injection on

postoperative analgesia. Berl Munch Tierarztl Wochenschr1998;111(1112):43851.

2. Kona-Boun JJ, Cuvelliez S, Troncy E. Evaluation of epidural administration of morphine or morphine and

bupivacaine for postoperative analgesia after premedication with an opioid analgesic and orthopedic surgery indogs.J Am Vet Med Assoc2006;229:11031112.

3. Hamilton SM, Johnston SA, Broadstone RV. Evaluation of analgesia provided by the administration of epidural

ketamine in dogs with a chemically induced synovitis. Vet Anaesth Analg 2005;32:3039.

4. Rao KNM, Rao KV, Makkera S, Naidu KS. Ketamine as epidural anaesthetic in dogs. Indian Vet J1999;76:6162.

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