Epidural and Spinal Anesthesia and Analgesia in the Equine

Epidural and Spinal Anesthesia and Analgesia in the Equine Cláudio C. Natalini, DVM, MS, PhD,* and Bernd Driessen, DVM, PhD, Dipl. ACVA & ECVPT†,‡ In human and animal anesthesia, epidural and spinal administration of drugs is used to provide surgical anesthesia and/or postoperative analgesia. Several local anesthetic drugs are used to produce epidural anesthesia, such as lidocaine, bupivacaine, ropivacaine, and mepivacaine. Epidural analgesia is obtained with opioid agonists, alpha2-adrenergic agonists, and ketamine. In horses, caudal epidural anesthesia is used to desensitize the anus, rectum, perineum, vulva, vagina, urethra, and bladder. The goal is to produce surgical regional anesthesia without losing motor function of the hind limbs. A combination of a local anesthetic drug with an alpha2-adrenergic agonist or an opioid is the most popular option as this combination extends the period of action of the epidural anesthesia or analgesia in horses, humans, and small animals. Spinal analgesia and anesthesia has not been used in horses as an adjunct to general anesthesia as much as it has in small animals and human beings. The epidural administration of opioids with or without local anesthetics is commonly performed in dogs and cats before surgery to reduce general anesthetic requirements as well as to provide intraoperative and postoperative pain control. The perioperative use of epidural and spinal analgesia in horses is likely to increase in the future as recent studies have shown that administration of epidural or subarachnoid alpha2-adrenergic agonists, phencyclidines, opioids, and low-dose local anesthetic produce intense antinociceptive effects. Clin Tech Equine Pract 6:145-153 © 2007 Elsevier Inc. All rights reserved. KEYWORDS horses, analgesia, anesthesia, pain, opioids, epidural, subarachnoid, spinal, hyperbaric

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he use of sensory blocks of spinal nerve fibers is known to produce anesthesia and analgesia in humans and animals. This technique is well established in human medicine and small animals. In the horse, epidural blocks are greatly accepted and started being used after studies showed the effectiveness and safety of their use. Two types of spinal blocks are usually used in horses: the epidural single injection or continuous infusion through an epidural catheter and the subarachnoid or intrathecal (spinal) single injection or continuous infusion through a subarachnoid catheter. Epidural analgesia has gained wider acceptance in horses and has permitted the administration of multiple injections

*Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre. †Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA. ‡Department of Anesthesiology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA. Address reprint requests to Cláudio C. Natalini, DVM, MS, PhD, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil 90046-900. E-mail: [email protected]

1534-7516/07/$-see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.ctep.2007.05.008

of analgesics and anesthetics for long durations of pain control. In horses, caudal epidural anesthesia is used to desensitize the anus, rectum, perineum, vulva, vagina, urethra, and bladder. The goal is to produce surgical regional anesthesia without losing the motor function of the hind limbs. A combination of a local anesthetic drug with an alpha2-adrenergic agonist or an opioid is the most popular option as this combination extends the period of action of the epidural anesthesia or analgesia in horses, humans, and small animals. Epidural or spinal analgesia and anesthesia has not been used in horses as an adjunct to general anesthesia as much as it has in small animals and human beings. The epidural administration of opioids with or without local anesthetics is commonly performed in dogs and cats before surgery to reduce general anesthetic requirements as well as to provide intraoperative and postoperative pain control. In the past 6 years, there have been many recent advances in spinal techniques in horses, both epidural and subarachnoid, to identify drugs or drug combinations that will have sensory effects without motor nerve paralysis, thus providing pain control without these horses becoming recumbent. Opioids, alpha2 agonists, dissociative drugs, and others have 145

146 been investigated. Many of these drugs, which have serious side effects when injected systemically in horses, have been shown to have very useful analgesic effects when injected spinally. Morphine-like opioids are the substances that have the greatest potential for spinal use as they produce longlasting analgesia without motor effects. Often the doses used spinally are significantly lower than those needed for systemic effects.

Anatomy Related to Spinal and Epidural Injections The spinal cord and meninges of horses generally terminate in the mid-sacral region. To access the spinal canal for a subarachnoid injection, the space between the sixth lumbar and the second sacral vertebrae at the midline depression should be located (see subarachnoid injection technique). The depth at the lumbosacral joint from the skin to the spinal canal varies from 15 to 20 cm,1 which limits the usefulness of this site for a single epidural injection, although it is the ideal location for a combined spinal– epidural technique. In the horse, the perineal–inguinal region is innervated by the coccygeal roots of the pudendal and caudal rectal nerves, and by the ventral branches of lumbar nerves L1 to L3. The sacral region is innervated by the caudal cutaneous femoral nerve originating from sacral nerves S1 and S2, and by sacral nerves S1 to S5. The lumbar region is innervated by lumbar nerves L1 to L6. The thoracic area is innervated by thoracic nerves T8 to T18. Studies on spinal analgesic techniques have shown that analgesia is produced up to the thoracic region with epidural or subarachnoid morphine or methadone.2 The sacrococcygeal joint may be fused in some horses. An imaginary line joining the two hip joints crosses the midline of the sacrococcygeal joint. The spinous process of the first coccygeal bone and, caudally, the first intercoccygeal joint can be palpated in thinner horses. The first intercoccygeal joint is often the first moveable joint in the tail and can be seen and palpated when the tail is raised and lowered. It lies approximately 2.5 to 5 cm cranial to the origin of the tail hairs. This joint is at the level of the caudal skin folds that can be seen at each side of the tail when it is raised. Skin, variable amounts of fat, and connective tissue between the dorsal vertebral spinous processes and the interarcuate ligament (ligamentum flavum) overlie the epidural space. The aperture between the two coccygeal vertebral arches, the interarcual space, can be relatively small in horses compared with cattle and sometimes difficult to locate with the needle. The epidural space at this level contains the nerves of the cauda equina, venous sinuses, and epidural fat. The perpendicular (90°) depth from the skin to the first intercoccygeal space is approximately 3.5 to 8.0 cm.3 In one study in which the needle was angled 10° to 30° to the spinal cord, and the needle tip passed cranially to S5 (sacral vertebra 5), and the distance measured from skin to epidural space was 8.5 ⫾ 0.5 cm.4 The anatomic site for segmental dorsolumbar epidural anesthesia is the T18–L1 space and has been described.5 Difficulties with entering the space and catheter placement in horses have limited the clinical usefulness of this technique.6

C.C. Natalini and B. Driessen

Supraspinal Processing of Nociceptive Information Nociceptive information is transmitted to supraspinal structures via ascending tracts. Although the neurotransmitters located within the ascending tracts are not known, the activation of supraspinal areas is probably mediated by excitatory aminoacids (EAAs).7 Collateral innervation in the ascending tracts is responsible for simultaneous activation of several brain regions when an ascending nociceptive stimulus is produced.8 The activation of supraspinal sites is necessary for the perception of pain. The supraspinal sites that process nociceptive information receive several afferent inputs and send out numerous efferents. The activation of systems of descending inhibition is already described.9,10 Several studies have shown that multiple areas within the brain contribute to the system of descending inhibition. Morphine and morphine-like agents will activate systems of descending inhibition similar to endogenous enkephalins.

Nociceptive Processing Within the Spinal Cord Painful stimuli are relayed to the spinal cord through A␦ and C fibers.11 These first-order neurons synapse with secondary neurons in the spinal cord. Release of nociceptive neurotransmitters from these primary afferent fibers activates second-order dorsal horn neurons in the spinal cord. Nociceptive-specific neurons transmit painful stimuli exclusively, and wide dynamic range neurons transmit nonpainful signals. The quantitatively most important spinothalamic tract ascends the spinal cord in the ventral white matter contralateral to the site of the stimulation.12 The activation of these neurons results in spinal reflex responses as well as activation of ascending tracts, which transmit nociceptive information to supraspinal levels to complete the nociceptive pathway.12,13 Substance P has been localized in small-diameter primary afferent fibers14,15 that terminate in the area of the substantia gelatinosa. The release of substance P from spinal cord has been demonstrated in vitro as well as in vivo.16,17 Other neuropeptides as well glutamate and ATP are released from the primary afferent neurons after nociceptive stimulation.18 Modulation may occur either by inhibiting the release of neurotransmitters from primary afferent fibers or inhibiting the activation of second-order dorsal horn neurons.

The Descending Modulation of Nociception It was demonstrated that descending inhibitory systems are involved in antinociception and analgesia because spinal nociceptive reflexes and complex behavior produced by nociceptive stimuli are inhibited in rats, cats, and monkeys, and analgesia is produced in man by electrical stimulation of the area of the periaqueductal gray (PAG) or opioid administered into the same brain structures.19 It is not known whether differing types of nociceptive input will activate different supraspinal regions to regulate descending inhibition differentially.13 Intrathecal administration of receptor selective antagonists has demonstrated a

Epidural and spinal anesthesia and analgesia noradrenergic and a serotoninergic component mediating descending inhibition from a variety of supraspinal sites.13 Numerous peptides and neurotransmitters have been localized in the PAG, including enkephalin, dynorphin, neurotensin, substance P, and others. This region of the midbrain is a site of descending inhibition. The PAG was the first brain site implicated in morphine-produced analgesia.20 Several opioid receptors, such as ␮, ␦, and ␬, have been demonstrated to be present in the PAG.21,22

The Importance of Opioid Receptors and Spinal Analgesia Presynaptic inhibition of the release of neurotransmistters from small-diameter afferent neurons within the dorsal horn of the spinal cord has been proposed as a mechanism of action for spinal antinociceptive agents. Evidence for a postsynaptic and a presynaptic action of spinal opioids has been reported. Opioid agonists inhibit the firing of the second-order dorsal horn neurons. The intrathecal administration of opioid agonists inhibits the nociceptive behavior produced by intrathecal injection of substance P. These observations provide evidence of a postsynaptic mechanism of action.16,23

Analgesic Effects of Epidural Opioids Based on the fact that there are opioid receptors in the substantia gelatinosa of the spinal cord, these agents have been used to control acute and chronic pain, producing effective and often prolonged analgesia.24,25 Analgesia that follows epidural placement of opioids reflects diffusion of the drugs across the dura mater to gain access to and activate opioid receptors in the spinal cord. Activation of ␮ opioid receptors is primarily responsible for supraspinal and spinal analgesia. Activation of the ␮1 receptor is speculated to produce analgesia, and activation of the ␮2 receptor is responsible for hypoventilation, bradycardia, and physical dependence.25 There is evidence that analgesia results from a regional effect, although systemic absorption occurs and may be responsible for some of the analgesic effects of epidural administered opioids.24 It has been reported that highly lipophilic opioids, such as fentanyl and its derivatives, produce analgesia primarily due to systemic absorption and there would be no advantage in injecting these agents epidurally.25,26 Pharmacokinetic studies have found no correlation between analgesia and plasma concentration of opioids, and analgesia is present with no morphine detectable in plasma.27 There is a relationship between lipid solubility and both onset and duration of analgesia. Onset of analgesia is slowest with morphine when compared with fentanyl, but the duration of analgesia is significantly longer.25 Opioids administered in the epidural space may be taken into epidural fat, systemic absorption or diffuse across the spinal meninges into the cerebrospinal fluid (CSF).24,25 Studies have shown a dose-response relationship between epidural opioids and analgesia. Doses of morphine of 2, 4, and 8 mg were more effective than 0.5 and 1.0 mg in human beings.28 These results suggest that more hydrophilic opioids are more effective

147 and the analgesic effects last longer than with more lipidsoluble agents.

Adverse Effects of Opioid Analgesics in the Horse In horses, systemic opioid administration has been reported to produce central nervous system (CNS) excitation in contrast to sedation in human beings and dogs.29 Both sympathetic and CNS excitation have been reported with different morphine-like opioids. Doses that provide cutaneous analgesia in horses increase the heart and respiratory rates, produce mydriasis and hyperthermia, and increase locomotor activity. It has been suggested that ␮3-opioid receptor agonists such as morphine and fentanyl increase the dopaminergic activity of the substantia nigra, a locomotion-activating center in the CNS that can be reduced with a dopamine receptor antagonist such as acepromazine.30 However, recent studies demonstrated that neither dopamine1 nor dopamine2 antagonists were effective to prevent opioid-induced excitement in horses.31,32 It has been shown that the opioid receptors in the CNS are responsible for the increased locomotor activity in the horse. When an opioid receptor antagonist such as naloxone is administered intravenously to horses, there is no increase in locomotor activity after ␮-opioid agonists such as morphine and fentanyl.33

Epidural and Spinal Analgesics and Anesthetics in the Horse In 1990, the first use of epidural morphine in horses was reported to treat severe somatic pain due to trauma in the rear limb in a mare.34 The authors reported that intractable pain refractory to systemic analgesic administration was successfully controlled with epidural morphine. Later, in 1994, a controlled study proved that epidural morphine in doses from 0.05 to 0.1 mg/kg produced segmentally distributed analgesia in horses characterized by sedation and no ataxia; with the higher dose producing a faster onset of analgesia, longer duration, cranial spread, and affecting several dermatomes in more horses than the lower dose. Dorsal nerve branches of the lumbosacral plexus were preferentially affected compared with ventral branches at the two doses of morphine given.35 The combination of morphine and the alpha2-adrenoceptor agonist detomidine was investigated given epidurally to horses in an amphotericin-B-induced synovitis of the left tarsocrural joint model. The authors concluded that there was a significant decrease in lameness scores after treatment with epidural morphine and detomidine, suggesting that the combination produces profound hindlimb analgesia in horses.36 In another experimentally controlled study, epidural morphine decreased the minimum alveolar concentration (MAC) of halothane in ponies when noxious stimulation was applied to the pelvic limbs but had no effect on MAC when the thoracic limb was stimulated. In the same study, epidural butorphanol produced no change in MAC.37 Neuraxial blocks such as spinal and epidural blocks with local anesthetics result in sympathetic block, sensory analgesia, and motor block. Despite these similarities, there are significant physiologic and pharmacologic differences. Spi-

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Figure 1 (A-D) Step-by-step illustration of placing a 20-gauge radiopaque and closed-tip polyamide epidural catheter into the first intercoccygeal space using an 18-gauge, 3.5-inch (8.9-cm) Tuohy Schliff epidural needle for entrance into the epidural space (Perifix® epidural catheter set; B. Braun Medical, Inc., Bethlehem, PA; product code CE-18T). See text and Table 1 for more detailed information. (Color version of figure is available online.)

nal anesthesia requires a small mass or volume of drug, virtually devoid of systemic pharmacologic effect to produce profound, reproducible sensory analgesia. In contrast, epidural anesthesia necessitates use of a large mass or volume of local anesthetics that produces pharmacologically active systemic blood levels, which may be associated with side effects and complications.38 Density is defined as the weight in grams of 1 mL of solution. Density is a major determinant of the distribution, duration, and degree of the clinical block achieved in spinal (subarachnoid) anesthesia with local anesthetics.39 Subarachnoidally administered local anesthetics and alpha2-adrenergic agonists to obtain segmental analgesia in horses have been extensively described.40,41 Subarachnoid administration of hyperbaric opioids was recently described in the horse.2 Analgesia obtained after the subarachnoid administration of hyperbaric opioids in horses was considered intense when methadone or morphine was used. Advantages of using hyperbaric opioids subarachnoidally versus epidural are that the intrathecal route is a direct one since there is no dura to be penetrated and the drug is deposited close to its site of action, the opioid receptors. Compared with the intrathecal route, epidural administration is complicated by pharmacokinetics of dural penetration, epidural fat deposition, and systemic absorption. To spinally administer local anesthetics and analgesics in the horse, proper technique should be used to prevent trauma to the vertebral bones and surrounding soft tissue, as well as to the vessel around the vertebral canal, and to the spinal cord.

Epidural Injection and Catheterization Techniques (Fig. 1) Caudal Epidural Injection For caudal epidural injections in adult horses, an 18-gauge, 7.5-cm sterile spinal needle with stylet is placed in the first intercoccygeal space in standing horses held in stocks (cf.

Fig. 1A). A regular 20-gauge, 3.75-cm hypodermic needle has also been used.1 The space is located by palpation while manipulating the tail in a dorsoventral direction. The skin over the region is clipped and surgically prepared. After location of the first intercoccygeal vertebral space, the skin and subcutaneous tissue above the space are desensitized by administration of 3 mL of 2% lidocaine or 2% mepivacaine, using a 5/8-inch (16-mm), 25-gauge needle. An adhesive clear plastic fenestrated dressing (Bioclusiv® transparent dressing; Johnson & Johnson, Arlington, TX) can be placed over the site to prevent contamination. In thick-skinned horses, making a small skin incision with a #15 scalpel blade or an 18-gauge needle helps needle insertion. The spinal needle is introduced perpendicularly to the skin with the bevel directed cranially, and pushed down in the median plane until the interarcuate ligament (ligamentum flavum) is perforated. Often a popping sensation is detected when the ligament is crossed. If the needle is inserted down to the bony floor of the vertebral canal, it should be withdrawn about 0.5 cm to avoid injection into the intervertebral disc. Before injection, correct placement of the needle in the epidural space is always verified using the Hanging drop or Loss of resistance technique. In case of the former, the stylet is removed from the spinal needle soon after passage of the skin and subcutaneous tissue, and a drop of sterile saline solution entered into the hub of the needle (see Fig. 1B); once the epidural space has been entered, the saline drop is aspirated into the needle due to the negative pressure in the epidural space. In case of the latter technique, the stylet is removed from the spinal needle as soon as a sudden loss of resistance is noted following penetration of the interarcuate ligament (ligamentum flavum), and a 5- or 10-mL syringe filled with air is tightly attached to the needle; lack of any resistance to air injection indicates correct positioning of the needle. Alternatively, a 5- or 10-mL syringe filled with sterile saline and an air bubble may be attached to the spinal needle; lack of any deformation or compression of the air bubble

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Table 1 Drug Regimens Used for Spinal (Epidural) Anesthesia/Analgesia and Reported Volumes and Dosages Drug (a) Single drug Lidocaine 1–2% Lidocaine 1% Mepivacaine 2% Bupivacaine 0.2–0.5% Ropivacaine 0.2–0.5%

Volume (mL)

Site of Injection

Duration of Effect (hrs)

5–8 20 5–8 5–8 5–10

Co1-Co2 Co1-Co2 Co1-Co2 Co1-Co2 Co1-Co2

0.75–1.5 3 1.5–3 3–8 3–8

Xylazine 0.17 mg/kg Detomidine 30 ␮g/kg Medetomidine 2–5 ␮g/kg Morphine 0.05–0.2 mg/kg

10 10 10–30 10–30

Co1-Co2 Co1-Co2 Co1-Co2 Co1-Co2

1.0–1.5 2–4 4–6 3–16

Methadone 0.1 mg/kg Tramadol 1 mg/kg Ketamine 0.5–2.0 mg/kg Hydromorphone (b) Drug combinations (“balanced regional analgesia”) Lidocaine 2% ⴙ Xylazine 0.17 mg/kg Lidocaine 2% ⴙ Morphine 0.1–0.2 mg/kg Bupivacaine 0.125% ⴙ Morphine 0.1–0.2 mg/kg Ropivacaine 0.008– 0.125% ⴙ Morphine 0.1–0.2 mg/kg Xylazine 0.17 mg/kg ⴙ Morphine 0.1–0.2 mg/kg Detomidine 30 ␮g/kg ⴙ Morphine 0.1–0.2 mg/kg Lidocaine 1–2% plus

20 10–30 10–30 10–30

Co1-Co2 Co1-Co2 Co1-Co2 Co1-Co2

5 4–5 0.5–1.25 4–5

5–8

Co1-Co2

4–6

5–8

Co1-Co2

4–6

10–30

Co1-Co2/L-S

8–>12

10–30

Co1-Co2/L-S

8–>12

10–30

Co1-Co2/L-S

>12

10

Co1-Co2/L-S

24 – 48 6–8 0.75–1.5

Morphine 0.1–0.2 mg/kg ⴙ Bupivacaine 0.125%

5 30 (together)

Co1-Co2 L-S

in the syringe during saline injection indicates the correct position of the spinal needle. To ensure that a venous sinus is not inadvertently penetrated, aspiration is always performed before injection of the epidural agents. Alternatively, a spinal needle can be inserted at the first intercoccygeal space by angling the needle ventrocranially at an angle of 10° to 30° to the spinal canal. Studies have shown the tip of the needle in the epidural space is generally at the Co1 to S5 intervertebral space.42 The length of needle used should be longer, and either an 18-gauge, 8.75-cm or 15-cm spinal needle has been recommended. This approach to the epidural space can be useful in horses that have developed fibrous tissue over the intercoccygeal space after previous epidural injections. The amount and volume of anesthetic/analgesic injected depends on the type of drug and the size and conformation of the horse (see also Table 1). If local anesthetic standard concentrations (lidocaine 2%, mepivacaine 2%, bupivacaine 0.50.75%, or ropivacaine 0.5-0.75%) are used, usually less than 10 mL are injected in adult horses to avoid paralysis of the lumbosacral nerves to the hind limbs.1 For single injections of analgesic solutions, total volumes of 10 to 20 mL can be

12–>24

Comments Repeated injections of 3 mL at 1-hour intervals Causes moderate ataxia

Fast onset (10 min); vaso-constriction; less ataxia risk May cause sedation/ataxia May cause sedation/ataxia May cause mild sedation Also useful for CRI (0.5–2 mL/h) via epidural catheter

Also useful for CRI (0.5–2 mL/h) via epidural catheter Also useful for CRI (0.5–3 mL/h) via epidural catheter

mild to moderate pain (severe pain) Via Tuohy needle prior to epidural catheter placement Via epidural catheter ad-vanced >5 cm cranially

used in adult horses to produce cranial migration of the solution over 6 to 10 vertebral spaces.

Epidural Catheterization For an epidural catheter placement (Fig. 1A-D), the horse should be sedated, for example, with 1.0 mg/kg xylazine, administered intravenously. Epidural catheterization is performed using the same technique described above for caudal (ie, intercoccygeal) epidural injection. Many manufacturers produce epidural trays or kits that are suitable for use in the horse (eg, Perifix® epidural catheter set, B. Braun Medical, Inc., Bethlehem, PA; product code CE-18T; Arrow epidural anesthesia catheter®, Arrow International, Reading, PA).1,17 An epidural Huber point (Tuohy) needle should be used instead of a spinal needle. This needle design has a slight curve on the end which aids in catheter directional placement and is more blunted at the end so less likely to sever the catheter than a regular spinal needle. The authors recommend flushing the catheter with fresh prepared sterile heparinized (10 IU/mL) saline before insertion to avoid any blood

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Figure 2 (A, B) Attachment of an epidural catheter (A) via extension tubing to a light weight, battery powered, foam-padded ambulatory mini-infusion pump (Ace Medical Automed® 3400; insert in B) that can be mounted on the horse using a girdle and a horse boot (ie, Ice Horse® insulated leg wraps, Mackinnon Ice Horse, San Diego, CA), commonly used for ice packing of the lower extremity. This set-up allows continued epidural drug infusion at rates of 0.1 to 50 mL/hour with the option of administering additional boluses of predetermined volumes (0.1-50 mL) as needed to treat breakthrough pain. See text and Table 1 for more detailed information. (Color version of figure is available online.)

or fibrin clotting should blood contamination during the insertion procedure occur. The skin should be clipped, surgically prepared, and covered with surgical sterile drapes or clear plastic adhesive drape (Bioclusiv transparent dressing) to avoid catheter contamination (Fig. 1A). A disposable sterile or reusable 17gauge or 18-gauge, 7.5-cm epidural Tuohy needle (Reusable technique needle, Tuohy, thin wall; Becton Dickinson Inc., Franklin Lakes, NJ) is used to penetrate the epidural space (Fig. 1A). After confirmation of successful epidural puncture (Fig. 1B), a 19-gauge or 20-gauge epidural catheter is introduced through the needle up to the desired length (Fig. 1C). Generally, for injections in the sacral area, 2 to 4 cm of catheter is advanced cranially from the needle tip.1 Catheters have length marks that indicate how far the catheter has been introduced forward into the epidural space. Usually the catheter should be inserted no more than 30 cm into the epidural space to avoid catheter kink. One of the authors prefers using a spring-wire reinforced catheter, 19-gauge, 91.4 cm (Arrow epidural anesthesia catheter®; Arrow International, Reading, PA), that facilitates introduction and rarely kinks, although polyamide or a plastic catheter can be used. After the needle is removed and the catheter is placed, it must be secured to the skin using a butterfly tape that is sutured to the skin. A bacterial filter may be attached to the catheter connector. The site of catheter penetration should be covered with iodine paste and the region covered with sterile dressings and gauze sponges and an adhesive clear plastic dressing (Fig. 1D).43 After each drug injection, the catheter should be flushed with 0.9% saline. Any presence of blood in the catheter suggests vascular catheterization that should be ruled out before catheter use. Epidural catheters elicit inflammatory reactions that may become uncomfortable and increase risks of contamination. Catheter care includes daily inspection and flushing with saline or heparinized (10 IU/mL) saline and skin cleaning with antiseptic solution. Attachment of an epidural catheter to a light-weight, battery-powered ambulatory mini-infusion pump (eg, Ace Medical Automed® 3400; Curlin Medical, Huntington Beach, CA;

see Fig. 2A and B) or a viscoelastic pump (eg, ON-Q® system; I-Flow Corp., Lake Forest, CA) that can be mounted on the horse allows continued epidural drug infusion. Continuous drug infusion reduces the risk of catheter contamination associated with intermittent drug administration and reduces the risk of early plugging of catheters. Epidural catheters have been kept in place for up to 28 days. The authors recommend that an intercoccygeal epidural catheter is placed should a highly lipophilic drug such as fentanyl or butorphanol be used. The epidural catheter should be passed cranially to the lumbosacral area (30 cm) for rapid and complete action of the drug on the spinal cord receptors. This technique is easier than passing a long spinal cord needle (17.78 cm) into the lumbosacral epidural space.

Subarachnoid (Spinal) Injection and Catheterization Technique (Fig. 3) The correct region for subarachnoid catheter placement is determined by palpating the caudal borders of the tuber coxae, the cranial borders of the tuber sacrale, and the midline depression between the sixth lumbar and the second sacral vertebrae. After sedation, the lumbar–sacral vertebral interspace should be clipped and the skin surgically prepared and covered with a sterile transparent dressing as described above (Fig. 3). After having identified the midline depression between the sixth lumbar and the second sacral vertebrae (Fig. 3B), the skin, subcutaneous tissue, and muscle at the lumbar–sacral region, the supraspinous and interspinous ligaments are locally anesthetized with 2% lidocaine (Fig. 3C). A 17-gauge, 17.78-cm epidural needle with stylet is inserted perpendicularly along the median plane of the lumbar–sacral intervertebral space, until the lumbar–sacral subarachnoid space is reached (Fig. 3D). To confirm the successful subarachnoid needle placement, the needle stylet is removed, and a clear cerebrospinal fluid sample should be withdrawn into a syringe (Fig. 3E). After appropriate placement, the bevel of the needle is directed cephalad and 20 cm of a sterile

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Figure 3 (A-G) Step-by-step illustration of placing a 19-gauge radiopaque, 91.4-cm polyurethane, spring-wire reinforced epidural and/or subarachnoid anesthesia catheter at the LS junction. See text and Table 1 for more detailed information. (Color version of figure is available online.)

19-gauge, 91.4-cm polyurethane spring-wire reinforced epidural anesthesia catheter (Arrow Epidural anesthesia catheter®; Arrow International, Reading, PA) is advanced cranially through the needle into the subarachnoid space (Fig. 3F). The epidural needle is removed and the catheter is left in place, sutured to the skin and covered with sterile transparent dressing and sterile gauze sponges (Fig. 3G). After each drug injection, the catheter should be flushed with saline. Any presence of blood in the catheter suggests vascular catheterization that should be ruled out before catheter use. As with epidural catheters, subarachnoid catheterization elicits inflammatory reactions that may become uncomfortable and increase risks of contamination. The catheter is flushed with 1 mL of heparinized (10 IU/mL) saline or with nonheparinized saline.

Risks, Side Effects, and Complications Associated with Repeated or Continuous Epidural and Spinal Anesthesia and Analgesia Systemic absorption of epidurally administered drugs, especially the alpha2 agonists and lipid soluble opioids, can

lead to sedation (Table 1). Sedation can be manifested as reduced response to external stimuli and by drooping of the head and lower lip. Standard doses of epidural anesthetics occasionally may cause severe ataxia and recumbency in horses (Table 1). This is particularly true for combinations of local anesthetics and alpha2 agonists or opioids (for instance, lidocaine and xylazine).44 The cause is not always apparent. Spread of local anesthetic too far cranially can paralyze the lumbosacral nerves in pregnant mares or obese horses in which the epidural space is narrowed. Additive effects of combinations of drugs administered epidurally, weakness of the horse from primary disease, or exhaustion or combinations of systemically administered sedatives with analgesic drugs administered epidurally may also contribute. Subarachnoid administration of ␮-opioid agonists may elicit CNS excitation. Cranial migration of subarachnoidally administered ␮-opioid analgesics such as morphine may lead to accumulations of high concentrations of the opioid in supraspinal structures of the CNS similar to what is seen after intravenous administration, increasing locomotor activity and sympathetic excitation (Natalini, unpublished observation). Recent studies have shown that adding 10% dextrose to ␮ opioids (morphine, methadone), producing a hyperbaric solution,

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152 does not elicit CNS excitation when the solution is administered subarachnoidally in horses.2 If motor impairment should occur (as is not uncommon after spinal local anesthetic or alpha2 agonist administration) if the horse is still standing, it can be supported with a tail-tie until strength in the limbs is regained. If it becomes recumbent, then general anesthesia or deep sedation may be necessary to continue surgery and/or to avoid agitation and distress of the patient. Clinical reports described recumbency in horses after caudal epidural anesthesia and lumbosacral epidural anesthesia.41,44 Recovery after general anesthesia and completion of surgery in one horse took approximately 300 minutes after a single injection of 60 ␮g/kg detomidine41 and in another horse 330 minutes after 0.22 mg/kg lidocaine plus 0.17 mg/kg xylazine.44 Both repeated administration and continuous infusion (at 0.5-2.0 mL/hour) of 0.125% bupivacaine or 0.125% to 0.2% ropivacaine via a caudal epidurally inserted catheter (with or without 1-2% morphine) does not seem to cause any notable impairment of motor function (Driessen, unpublished observation). This observation coincides also with data in humans45,46 and applies particularly to ropivacaine. Ropivacaine, which is a new long-acting local anesthetic with fast onset of action that is structurally similar to bupivacaine but less cardiotoxic, has been given by continuous epidural infusions to humans for pain relief following orthopedic and abdominal procedures.47,48 The greater dissociation between sensory and motor block, and the improved clearance in comparison with bupivacaine, makes ropivacaine particularly suitable for continuous administration.49 Inadequate analgesia or anesthesia may occur due to improper technique, anatomic abnormalities, and fibrous adhesion from previous epidural injections and can cause failure of the technique.1 Segmental distribution of analgesia has been reported after epidural administration of morphine in horses, in which dorsal dermatomes innervated by lumbosacral nerves had superior analgesia to ventral dermatomes.35 This would result in inadequate analgesia in ventral areas of the hindlimb in some horses. Unilateral blockade with local anesthetics might be due to presence of congenital membranes in the epidural space, or adhesions. Incorrect epidural catheter placement due to ventral epidural placement, or placement through an intervertebral foramen, could also result in unilateral blockade.50 Neurotoxicity due to damage to the nerves and spinal cord by epidural solutions is a controversial issue. Reports indicate that clinical doses of local anesthetics used in horses cause no neurotoxicity, whereas in rodents, solutions containing the antioxidant sodium bisulphate have produced neuronal damage.1 The pH of solutions is another possible cause of neuronal injury, although local anesthetics are only mildly acidic.1,51 Solutions that contain no preservatives should be used whenever possible. Large volumes of epidural solutions may cause pain in the spinal canal of horses due to compression of sacral and lumbar nerves.52 Edematous skin wheals in the perineal area have been seen in some horses after morphine injection, and may be associated with local histamine release.35,43 Bradycardia and second-degree atrioventricular block have been described after injections of alpha2-agonist.41 No adverse cardiovascular effects were observed after epidural or subarachnoid ␮-opioid agonists in horses.2,43 When using a spinal analgesic technique, side effects and

complications should be considered. Side effects should be reversible with an antagonistic drug. Duration should be compatible with the procedure to be performed (Table 1). Motor and sensory blockade should be expected with local anesthetics in higher concentrations.

Clinical Applications of Epidural and Spinal Analgesics The clinical application of epidural or spinal analgesics in horses is recommended for short- and long-term pain control of the rear limb, perineum, tail, and abdominal wall. Time to effect is influenced by the number of molecules retained in the cerebrospinal fluid and spinal tissue, and by the dissociation kinetics of the drug.1,2,43 Thus, there are differences in onset, spread, and duration that can vary with each drug. Epidural morphine produces profound analgesia, although the long onset of action precludes its use alone in acute cases without combination with faster-acting epidural analgesics, such as alpha2-agonists or fentanyl (Table 1). Tramadol has also been combined with fentanyl in horses in severe intractable pain (Natalini, unpublished observations). Subarachnoid hyperbaric morphine and methadone have shown to produce fast-acting and intense analgesic effects. This technique can be recommended for acute pain control because of the faster onset of action compared with epidural administration. Placing a subarachnoid catheter is recommended for long-term pain control when hyperbaric subarachnoid opioids are the treatment of choice.2 This allows for repeated administration without the hazards of multiple punctures. Care should be taken to prevent contamination of the spinal meninges and the spinal cord. For standing surgeries, the lack of motor impairment and profound analgesia produced by epidural morphine, hydromorphone, methadone, and tramadol or subarachnoid hyperbaric morphine and methadone, suggest that these drugs may be combined with low doses of local anesthetics such as lidocaine, mepivacaine, bupivacaine, or ropivacaine to produce long-lasting surgical anesthesia/analgesia and prolonged postoperative pain relief without the risks of ataxia or recumbency (Table 1). Surgical procedures in the perineal and sacral areas could be performed using this anesthetic/ analgesic technique. Laparoscopic surgeries involving the urogenital tract could also be conducted after administration of an opioid/local anesthetic combination.

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