Pain Management via Locoregional (Epidural) Approach Beyond Sodium Channel Blockers
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 largely subdivided 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.
Anatomy and Techniques of Epidural Anesthesia in Dogs and 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.
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.
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 anesthetic 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 1–2 mg/kg of lidocaine or 0.5–1 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.
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 if morphine (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.
The examples of NMDA (n-methyl-d-aspartate) antagonist in veterinary use are ketamine and tiletamine. 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 anesthesia are conflicting. Rao et al reported 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.
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.
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 Wochenschr 1998;111(11–12):438–51.
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 in dogs. J Am Vet Med Assoc 2006;229:1103–1112.
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;32:30–39.
4. Rao KNM, Rao KV, Makkera S, Naidu KS. Ketamine as epidural anaesthetic in dogs. Indian Vet J 1999;76:61–62.