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Vet Clin Equine 18 (2002) 61–82

Epidural anesthesia and analgesia in horses


Elaine P. Robinson, BVetMed, MVSca,*,
Claudio C. Natalini, DVM, PhDb
a
Division of Anesthesiology, Department of Small Animal Clinical Sciences,
College of Veterinary Medicine, University of Minnesota,
1352 Boyd Avenue, St. Paul, MN 55108, USA
b
Universidade Federal de Santa Maria, Departmento de Clinica de Pequenos Animais,
Hospital de Clinicas Veterinarias, Santa Maria RS, Brazil 97.105–900.

History of epidural analgesia and anesthesia in horses


The practical application of epidural injection of local anesthetics in
horses was first described in Germany and later in England over 75 years
ago [20]. Deposition of local anesthetics into the epidural space of the horse
in the sacrococcygeal or intercoccygeal area was a convenient approach to
providing complete loss of sensory and motor function to the tail and peri-
neum in the standing horse, and avoided many of the hazards of general an-
esthesia and recumbency. Before this time cocaine was the only local
anesthetic available, but with the discovery of procaine and then lidocaine,
safer drugs could be used for epidural anesthesia.
Why, then, has a procedure that has been reported and performed in
horses for so many years not gained wider acceptance in equine veterinary
practice? Technically, intercoccygeal epidural injection was found to be
somewhat more difficult in equine than bovine animals. Restraint for injec-
tion was, and still remains a problem, and often requires sedation in horses;
this can lead to a greater tendency of the horses to become ataxic or fall
down. Stocks or other forms of physical restraint are needed in many situa-
tions to prevent injury to the veterinarian by the horse during needle place-
ment. Contamination of the epidural space and resultant meningitis still
remains a hazard, unless strict asepsis is maintained; and this can be a prob-
lem in clinical equine practice in non-hospital situations. Initially, use of lo-
cal anesthetics for caudal epidural injections limited the veterinarian to
performing surgery and manipulations in areas of the tail and perineum.

* Corresponding author.
E-mail addresses: robin011@umn.edu (E.P. Robinson).

0749-0739/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved.
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Larger injections of local anesthetics (anterior block) caused recumbency of


several hours duration, which was difficult to manage in excitable or in sick
and depressed horses. While research in horses showed that lumbar epidural
local anesthesia can be performed, the approach is somewhat difficult and
thus this technique has not been widely adopted as a means of desensitizing
the flank [49]. More recently, placement of epidural catheters has gained
wider acceptance in horses and has permitted the administration of multiple
injections of analgesics and anesthetics for long durations of pain control.
In the last decade there have been many recent advances in epidural tech-
niques in horses, especially in the desire to find drugs that will have sensory
effects without motor nerve paralysis, thus provide pain control in the hind
limbs, without these horses becoming recumbent. Opioids, alpha-2 agonists,
dissociative drugs and others have 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 epidurally.
Often the doses used epidurally are significantly lower than those needed
for systemic effects.
Epidural analgesia has not yet become as well accepted in horses as an ad-
junct to general anesthesia as it has in small animals. Epidural injections of
opioids with or without local anesthetics are commonly performed in dogs
and cats before surgery to reduce general anesthetic requirements as well
as to provide intraoperative and postoperative pain control [57]. The peri-
operative use of epidural analgesia in horses is likely to increase in the future
as recent studies have shown that inhalant requirements are greatly decreased
by the injections of epidural xylazine, morphine, or ketamine [11,12].

Anatomy relevant to epidural injections


The spinal cord and meninges of horses generally terminate in the mid
sacral region [49]. The sacrococcygeal joint may be fused in some horses.
An imaginary line joining the two hip joints crosses the midline of the sacro-
coccygeal joint. The spinous process of the first coccygeal bone and, caud-
ally, 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 approxi-
mately 2.5–5 cm (1–2") 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, connective tissue between the dor-
sal 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 com-
pared to cattle, and sometimes difficult to locate with the needle. The epidur-
al 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
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intercoccygeal epidural space is approximately 3.5–8 cm [20]. In one study in


which the needle was angled 10–30° to the spinal cord, and the needle tip
passed cranially to S5 (sacral vertebra 5), the distance measured from skin
to epidural space was 8.5 ± 0.5 cm [51]. By comparison, the depth at the
lumbosacral joint is 15–20 cm which limits the usefulness of this site for epi-
dural injection [33].
The nerves of the lumbosacral area of horses have been reviewed [49]. Gen-
erally the coccygeal, and the sacral nerves S2 to S5 comprising the pudendal,
middle rectal, and caudal rectal are desensitized with local anesthesia to pre-
vent tenesmus and for surgeries of the tail, anus, rectum, vulva, vagina, urethra
and bladder. However branches of S2 also contribute to the caudal cutaneous
nerve innervating the lateral and posterior surfaces of the hip and thigh, and
blockade of this nerve with local anesthetic can cause ataxia and hindlimb
weakness [51]. Relevant spinal nerves affected by opioid and alpha–adrenergic
agonists include the coccygeal, lumbar and thoracic nerves, and there are sev-
eral reports of these agents causing loss of pain responses in dermatomes as far
cranially as thoracic nerve eight to fifteen (T8–T15) [34,40,43].
The anatomic site for segmental dorsolumbar epidural anesthesia is the
T18–L1 space and has been described [49]. Difficulties with entering the
space and catheter placement in horses have limited the clinical usefulness
of this technique [44].

Indications for epidural analgesia and anesthesia


Surgical procedures of the tail, anus, rectum, vulva, vagina, urethra and
bladder can be performed in the standing horse under caudal epidural injec-
tion of local anesthetic [44]. Additional drugs such as xylazine and detomi-
dine have been added to increase the intensity, reliability and duration of
local anesthetics but ataxia and recumbency are possible complications,
especially if systemic sedatives have also been administered [4,59]. Addi-
tional procedures such as surgical correction of prolapsed rectum, or cor-
rection of rectovaginal fistula, fetotomy, correction of uterine torsion,
laparoscopic cryptorchidectomy and perineal urethrotomy for relief of uro-
lithiasis, or for prevention of tenesmus are indications for local anesthetics
[18,28,49]. Alpha-2 adrenergic agonists have been used alone for a variety
of similar perineal surgical procedures [30]. Pain relief for surgical proce-
dures or for acute and chronic painful conditions associated with trauma
or inflammatory diseases of the hindlimb or pelvis of horses are indications
for epidural administration of opioids, alpha-2 agonists, ketamine, tramadol
or combinations of these drugs [54,58]. Placement of an epidural catheter
through the caudal epidural space, or occasionally through the lumbosacral
space into the sacral area, allows the veterinarian to give repeated doses of
analgesics immediately postsurgically (Fig. 1) or, alternatively, for days to
weeks while the horse recovers from a painful lesion (Figs. 2 and 3).
64 E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

Fig. 1. Horse with a rectal prolapse which was treated presurgically with 5 ml lidocaine (2%)
and 0.17 mg/kg xylazine by epidural catheter, followed in 12 hours by 5 ml lidocaine (2%) with
0.1 mg/kg morphine for prolonged pain and tenesmus control.

Fig. 2. Horse with bilateral ruptured annular ligament of the fetlock joint which received IV
flunixin meglumine and, through an epidural catheter, 1.0 mg/kg tramadol with 5 microgram/kg
fentanyl for two days, then 0.1 mg/kg morphine with 10–20 micrograms/kg detomidine daily for
4 weeks.
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82 65

Fig. 3. Horse with visible cellulites of the left hind limb. Pain was managed by placing an
epidural catheter and administering 0.1 mg/kg morphine with 10–20 micrograms/kg detomidine
daily for three weeks.

Techniques for epidural injection


Epidural injection
The standard technique to perform an epidural injection in adult horses
is to use an 18-gauge 3.0-inch (7.5 cm) sterile spinal needle with a stylet,
66 E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

although regular 20-gauge 1.5-inch (3.75 cm) hypodermic needles have also
been used [18,44,49]. The needle is placed in the first intercoccygeal space
with the horse held in stocks. The skin over the region is clipped and surgi-
cally prepared. After location of the first intercoccygeal vertebral space, the
skin and subcutaneous tissue above the space is desensitized by administra-
tion of 2–3 ml of 2% lidocaine or 2% mepivacaine, using a 5/8-inch (16 mm)
25-gauge needle. A fenestrated adhesive clear plastic 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 nee-
dle insertion. The spinal needle is introduced perpendicularly to the skin
with the bevel directed cranially, and pushed down in the median plane until
the ligamentum flavum is penetrated. Often a ÔpoppingÕ sensation is detected
when the ligament is crossed and even a hissing sound as the epidural space
is entered. A drop of sterile water or saline placed in the hub of the needle is
aspirated when the needle enters the epidural space (Ôhanging dropÕ tech-
nique). 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 interverteb-
ral disc. Before injection, correct placement of the needle in the epidural
space is verified by the hanging-drop technique and negligible resistance
to air or sterile-water injection [44,49]. Aspiration should always be per-
formed to ensure that a venous sinus was not penetrated.
Alternatively, a spinal needle can be inserted at the first intercoccygeal
space by angling the needle ventrocranially at an angle of 10–30° to the spinal
canal. Studies have shown the tip of the needle in the epidural space is gener-
ally at Co1 to S5 vertebral space [51]. The length of needle used should be
slightly longer and either an 18-gauge 8.75 cm or 15 cm spinal needle (Mono-
ject, Sherwood Medical, St. Louis, MO) has been recommended [50,51]. This
approach to the epidural space can be useful in horses that have developed fi-
brous tissue over the intercoccygeal space after previous epidural injections.
The amount of anesthetic injected depends on the type of drug, the size
and the conformation of the horse. If local anesthetic solution is used usually
<10 mls is injected in adult horses to avoid paralysis of the lumbosacral
nerves to the hind legs [18,44]. For single injections of analgesic solutions
total volumes of 10–20 ml can be used in adult horses to produce cranial
migration of the solution 6 to 10 vertebral spaces [21].

Epidural catheterization
Epidural catheterization is performed using the same technique described
above for intercoccygeal epidural injection [1,17,49,55]. Many manufac-
turers produce epidural trays or kits that are suitable for use in the horse
[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
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82 67

to sever the catheter than a regular spinal needle. 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. A disposable sterile or reusable 17 or 18-gauge 3" (7.5 cm)
epidural Tuohy needle is used to penetrate the epidural space. After confir-
mation of successful epidural puncture, a 19 or 20-gauge epidural catheter is
introduced through the needle up to the desired length. Generally for injec-
tions in the sacral area, 2–4 cm of catheter is advanced cranially from the
needle tip [49]. Catheters have length marks that are helpful to know how
far they are into the epidural space. Usually the catheter should be inserted
no more than 30 cm into the epidural space to avoid catheter kink. The
authors prefer 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 a 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 tape butterfly 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 re-
gion covered with sterile dressings and gauze sponges and an adhesive clear
plastic dressing (Fig. 4). After each drug injection the catheter should be
flushed with 0.9% saline. Any presence of blood in the catheter suggests vas-
cular catheterization that should be ruled out before catheter use. Epidural

Fig. 4. An epidural catheter placed in the first intercoccygeal space, and covered with a sterile
dressing.
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catheters elicit inflammatory reactions that may become uncomfortable and


increase risks of contamination [17]. Catheter care includes daily inspection
and flushing with 0.9% saline or heparinized (10 IU/ml) 0.9% saline and skin
cleaning with antiseptic solution.
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 needle (17.78 cm) into the lum-
bosacral epidural space [33].

Complications of epidural anesthesia in horses


Sedation and recumbency
Systemic absorption of epidurally administered drugs, especially the
alpha-2 agonists, opioids and dissociative drugs 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 of combinations of local anesthetics and
alpha-2 agonists (for instance, lidocaine and xylazine) [4]. The cause is not
always apparent. Spread of local anesthetic too far cranially can paralyse
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
the analgesic drugs administered epidurally may also contribute. Absorption
of epidurally administered drugs into the vascular system can be rapid and
systemic effects such as sedation have been seen after epidural injections of
detomidine, morphine, meperidine or ketamine (Table 1).
If the horse has significant hindlimb weakness, but is still standing, it can
be supported with a tail-tie until strength in the limbs is regained. If it be-
comes recumbent then general anesthesia is induced to continue surgery
or to control the horse if it is very agitated or distressed. Two clinical case
reports described recumbency in horses after caudal epidural anesthesia.
Recovery, after general anesthesia and completion of surgery in one horse
took approximately 300 minutes after a single injection of 60 micrograms/kg
detomidine [59] and in another horses 330 minutes after 0.22 mg/kg lidocaine
with 0.17 mg/kg xylazine [4].

Inadequate analgesia or anesthesia


Improper injection technique, anatomic abnormalities and fibrous adhe-
sions from previous epidural injections can cause failure of the technique
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[44]. Segmental distribution of analgesia has been reported after epidural ad-
minstration of morphine to horses, in which dorsal dermatomes innervated
by lumbosacral nerves had superior analgesia to ventral dermatomes [40],
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 [41].
Incorrect epidural catheter placement due to ventral epidural placement,
or placement through an intervertebral foramen could also result in unilat-
eral blockade [41].

Neurotoxicity
Damage to the nerves and spinal cord by epidural solutions is a contro-
versial 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 [44]. The
pH of solutions is another possible cause of neural injury, although local
anesthetics are only mildly acidic [19,44]. If possible, it is preferred to use
solutions that contain no preservatives. The number of commercially avail-
able preservative-free solutions at the correct concentrations and volumes
suitable for epidural injection in horses is limited. In one study comparing
opioid, kappa agonists and tramadol in horses, the authors had to use a
20-ml injectate volume as this was the volume dictated by the only available
solution of alfentanil [34]. Such large volumes may cause pain in the spinal
canal of horses due to compression of sacral and lumbar nerves [21]. One
study showed no histologic changes in the spinal cords of ponies after lido-
caine and xylazine epidural administration [15].

Other complications
Sweating is seen in the area effected by lidocaine or xylazine injection
[29,41]. Perineal edema has been observed after xylazine injection. Edema-
tous skin wheals in the perineal area have been seen in some horses after
morphine injection, and may be associated with local histamine release
[34,40]. Cardiovascular effects such as bradycardia and second-degree atrio-
ventricular block have followed xylazine or detomidine injection [46–48].

Epidural treatment protocols for horses


Ideally the drug or drugs chosen should have a high safety margin, high
efficacy, lack of side-effects. Side-effects should be reversible with an antag-
onistic drug. Duration should be compatible with the procedure to be per-
formed (Table 1). Motor and sensory blockade should be expected with the
local anesthetics; whereas sensory blockade alone is usual with many of
the other treatments.
70

Table 1
Recommended regimens (single injection) for epidural anesthesia and analgesia in horses reported in research studies and in clinical practicea
Duration
Onset of anesthesia
Drug or combination Doses of action or analgesia Adverse effectsb References
Lidocaine 0.22–0.35 mg/kg 5–15 minutes 60–90 minutes Ataxia or recumbency [1,15,18,19,32,41,43,44,49]
at higher doses
Lidocaine (2%) 5–8 mL per 450 kg
Mepivacaine (2%) 5–7 mL per 450 kg 10–30 minutes 90–120 minutes [42,43,49]
Ropivacaine (0.5%) 8 mL per 500 kg 5–15 minutes 2.5–4 hours Inadequate perineal analgesia [32,51]
Xylazine 0.17 mg/kg 10–30 minutes 2.5–4 hours Perineal edema and sweating [12,29,30,31,44,49]
Xylazine 0.35 mg/kg 10–20 minutes 3–5 hours Mild ataxia [15,26]
Detomidine 30–60 lg/kg 10–15 minutes 2–3 hours Sedation, ataxia, [45,46,48,49,59]
cardiovascular depression,
second-degree
atrioventricular block,
diuresis
Romifidine 80 lg/kg 10–20 minutes ? Inadequate perineal [25]
analgesia, bradycardia
Lidocaine and xylazine 0.22 mg/kg 5–15 minutes 5.5 hours Ataxia or recumbency, [4,19]
and 0.17 mg/kg perineal sweating
Morphine 0.1 mg/kg 4–6 hours 8–18 hours Skin wheals, sedation [11,34,35,40,54,58]
Morphine 0.1 mg/kg 20–30 minutes 20–24 hours Sedation, ataxia [54]
and detomidine and 10 lg/kg
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

Butorphanol 0.05–0.08 mg/kg NE NE [11,34]


Butorphanol and lidocaine 0.04 mg/kg ? 2.5 hours Change in hind limb gait [14]
and 0.25 mg/kg
Tramadolc 1 mg/kg 30 minutes 8–12 hours [34]
Tramadol and fentanyld 1 mg/kg and 5 lg/kg 30–60 minutes 12–18 hours
Meperidine 0.8 mg/kg 5–15 minutes 4–5 hours Mild sedation and ataxia [52]
Ketamine 0.5–2.0 mg/kg 5–10 minutes 30–90 minutes Sedation, mild ataxia [3,11,16]
with higher doses
Ketamine and morphined 1 mg/kg and 0.1 mg/kg 10–30 minutes 12–18 hours Sedation, mild ataxia
Ketamine and xylazine 1 mg/kg and 0.5 mg/kg 5–9 minutes >2 hours Mild sedation, bradycardia [26]
Tiletamine/zolazepam 0.5–1.0 mg/kg NE or mild analgesia NE or mild analgesia Moderate ataxia, central [36]
nervous system excitation
muscle fasiculations
a
Doses used in clinical practice may be lower to avoid potential complications.
b
Potential complications, rarely observed.
c
Injectable form not available in the United States.
d
C.C. Natalini, personal communication, 2001.
NE ¼ No analgesic effects reported.
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Local anesthetics
Lidocaine, mepivacaine
Local anesthetics have the potential to produce sensory, motor and sym-
pathetic neuronal blockade by depressing axonal conduction of nerves. Cau-
dal epidural local anesthesia in horses does not progress cranial enough to
produce sympathetic blockade cranial to the hind limb. Onset of local anes-
thetic effects is marked by relaxation of the tail and the anus. Standard vol-
umes of lidocaine and mepivacaine produce up to 90 to 120 minutes
respectively of local anesthesia in horses (Table 1) [1,43,44,49]. The longer
durations given can be achieved by adding a vasoconstrictor to the solution
such as epinephrine (0.05 ml of 1:1000 solution to 10 ml of local anesthetic
solution ¼ 1:200,000). After this time, if an epidural catheter is in place,
anesthesia can be prolonged by injecting half the original volume of local
anesthetic. Mild ataxia is common even when doses as low as 0.22 mg/kg
lidocaine are used [19]. Carbonated lidocaine has been studied in horses in
the hope of producing a more reliable and consistent sensory block after epi-
dural administration, with a faster onset than lidocaine alone, however, in
horses carbonated lidocaine offered no advantages over lidocaine alone [41].

Ropivacaine, bupivacaine
In humans, ropivacaine is a longer duration local anesthetic which pro-
duces less motor block than traditional local anesthetics like lidocaine.
Results of epidural administration of ropivacaine, (8–9 ml, 0.5% solution)
has been studied in standing mares [51]. Prolonged bilateral analgesia between
the coccyx and sacral dermatomes S2-4 was produced, with minimal seda-
tion, ataxia and circulatory and respiratory changes. In 5 of the 10 mares
studied, inadequate analgesia was thought to be due to incorrect needle place-
ment [51]. In another study in horses, in which the effects of lidocaine and
ropivacaine given epidurally were compared, ropivacaine (5.8 ml, 1% solu-
tion) combined with epinephrine 1:200,000, produced 285 minutes of
perineal analgesia, compared to 163 minutes with lidocaine (5.8 ml, 2% solu-
tion [32]. One mare receiving a combination of lidocaine and ropivacaine
became recumbent [32]. Some of the newer local anesthetics (dilute solutions
of bupivacaine and ropivacaine) are being investigated in humans for prefer-
ential sensory block after epidural or subarachnoid injection, but this
concept has not yet been studied in horses. There are no current reports
of the use of bupivacaine for epidural analgesia in horses.

Alpha-2 adrenergic agonists


The use of alpha-2 adrenergic agonists has become popular for caudal
epidural analgesia in horses due to the longer duration of activity than most
local anesthetics and the easy accessibility of this group of drugs for equine
practitioners. Unless recommended dose rate are exceeded, these drugs
do not produce motor blockade, thus horses remain standing, even if the
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analgesic effect spreads cranially into the lumbar and thoracic area. How-
ever, ataxia and recumbency are still possible complications of this group
of drugs in individual horses [59]. Compared to local anesthetics, but similar
to opioids, detailed studies have shown that alpha-2 agonists tend to pro-
duce variable or patchy segmental effects [46,47]. For this reason, xylazine,
other alpha-2 agonists, and the opiods are often combined with other drugs,
such as local anesthetics, for caudal epidural analgesia in horses [19].
Agonists of alpha-2 adrenergic receptors produce analgesia by their action
on receptors in the substantia gelatinosa of the dorsal horn of the spinal
cord. Xylazine may also have a local anesthetic-like action on spinal nerves.
Any adverse effects of epidurally administered alpha-2 agonists can be
reversed in horses by drugs such as atipamezole (40 micrograms/kg IV) or
yohimbine (50 micrograms/kg IV) [49,50].

Xylazine
Original work with xylazine compared various dose rates and concluded
that 0.17 mg/kg was the optimal dose given epidurally to horses to produce
2.5 hours of perineal analgesia, with no hindlimb ataxia (Table 1) [29]. This
dose is one half to one fifth the dose commonly given systemically for seda-
tion of horses. Xylazine was diluted in 10 ml of 0.9% saline for injection. At
this dose rate no sedation nor cardiorespiratory side-effects were noted [31].
In combination with other drugs (e.g., lidocaine) this dose of xylazine is still
frequently used [4,19]. For perineal surgeries, using xylazine alone, higher
dose of 0.22–0.25 mg/kg have been recommended [30,47,48]. Ponies receiv-
ing xylazine at 0.35 mg/kg for caudal epidural analgesia had mild ataxia [15].
A recent report used a high dose rate of xylazine (0.5 mg/kg) when combined
with ketamine for perineal analgesia [26]. Cardiorespiratory changes have
been recorded in mares administered 0.25 mg/kg xylazine, diluted in 6 ml
of saline, for caudal epidural analgesia [47]. All mares were mildly sedated.
Heart rate and respiratory rate decreased significantly, and 2° atrioventricu-
lar block developed in 7 of 8 mares. Arterial blood pressure initially in-
creased then decreased below normal. Perineal sweating was seen in all
mares 30 minutes after injection and persisted for 3 hours. Distribution of
bilateral analgesia varied between mares, from the coccygeal to S3 dermato-
mal segments. Blockade of motor nerves in 2 mares produced tail flaccidity
and hindlimb ataxia. Blockade of parasympathetic nerves resulted in relaxa-
tion of the genitalia and dilation of the rectum [47].

Detomidine
Potent analgesic and sedative effects are produced when detomidine is in-
jected into the caudal epidural space of horses [45]. Detomidine is a lipophi-
lic drug and is rapidly absorbed systemically from the epidural space.
Sedation, ataxia, recumbency, and cardiovascular effects can occur with
doses as low as 20 micrograms/kg. Thus, low doses (20–40 micrograms/kg)
74 E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

should be used initially in clinical cases in horses which are debilitated or


prone to recumbency.
Experimental studies in mares have shown that 60 micrograms/kg deto-
midine, made up to 10 ml with sterile water was optimal for production of
analgesia, doses <30 micrograms/kg were ineffective in producing reliable an-
algesia and higher doses >80 micrograms/kg produced marked side-effects
and recumbency [45,46]. Analgesia induced was variable, bilateral and spread
as far cranially as T14, with mild ataxia in all mares but no recumbency.
Detomidine effects were characterized by marked sedation in all horses, with
head drooping and a sleep-like state. Heart rate decreased, 2° atrioventricu-
lar block was seen in all mares and arterial blood pressure initially rose and
then decreased below normal [46]. Large amounts of urine were voided,
thus this drug would be contraindicated in a horse with obstruction to urine
flow. Compared to xylazine, the analgesic effects detomidine tends to spread
further cranially and the duration of analgesia is usually shorter (Table 1)
[48]. Cardiovascular depression, sedation and duiresis are more marked with
detomidine compared to xylazine [48]. In another study, administration of
intravenous yohimbine antagonized the analgesia, head ptosis, postural
changes and bradycardia in horses given detomidine epidurally [50].

Romifidine
In a recent report, romifidine at 80 micrograms/kg diluted in saline to
8.0 ml, produced no analgesia in 5 of 8 horses studied, and insufficient anal-
gesia for surgery in the other 3 horses. Sedation, bradycardia, and decreased
respiratory rate were reported [25].

Opioid analgesia in horses


The most potent pain relieving substances known are the opioid anal-
gesics, but these drugs are not used extensively in horses. Marked sympathetic
stimulation and central nervous system (CNS) excitation are observed when
opioids are intravenously administered in this species in contrast to sedation
in human beings and dogs [6,24]. Doses that provide cutaneous analgesia in
horses increase the heart and respiratory rates, produce mydriasis and hy-
perthermia, and increase locomotor activity. Mu opioid 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 [6–8]. Butorphanol, has
been reported to markedly increase the locomotor activity when intrave-
nously administered to horses [37]. Naloxone reversed this activity produced
by intravenous administration of morphine or fentanyl, showing that opioid
receptors in the CNS are responsible for the increased locomotor activity in
the horse [56].
Opioid analgesics are not commonly administered systemically in horses
for pain relief because of the CNS excitatory effects. The selective kappa
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82 75

opioid agonist U50488H has been shown to produce short-term analgesia


without CNS excitation after intravenous administration in horses [34].
Profound analgesia and sedation are obtained when an opioid such as mor-
phine is combined with xylazine or acepromazine [5,22,27,39].
These facts suggest that non-systemic administration route, such as the
epidural route, should be explored for opioid administration to horses, to
minimize side-effects while maintaining beneficial analgesic effects.

Opioid epidurals in horses


Morphine
In 1990 the first use of epidural morphine in horses was reported to treat
severe somatic pain due to trauma in the rear limb of a mare [58]. The
authors reported that intractable pain refractory to systemic analgesic ad-
ministration was successfully controlled with epidural morphine. Later, in
1994, a controlled study proved that 0.05 to 0.1 mg/kg epidural morphine
produced segmental distributed analgesia in horses characterized by seda-
tion and no ataxia; with the 0.1 mg/kg dose producing a faster onset of an-
algesia, longer duration, more cranial spread, and affecting several
dermatomes in more horses than the lower dose [40]. Dorsal nerve branches
of the lumbosacral plexus were preferentially affected compared to ventral
branches at the two doses of morphine given [40]. Recently the combination
of morphine and the alpha-2 adrenergic agonist detomidine was investigated
given epidurally to horses in an amphotericin-B induced synovitis of the left
tarsocrural joint model [54]. The authors concluded that there was a signifi-
cant decrease in lameness scores after treatment with epidural morphine and
detomidine suggesting that the combination produces profound hindlimb
analgesia in horses [54]. In another experimentally controlled study, epidural
morphine decreased the minimum alveolar concentration (MAC) of halo-
thane in ponies when noxious stimulation was applied to the pelvic limbs
but had no effect on MAC when the thoracic limb was stimulated [11]. When
compared to other opioids given epidurally to horses in a controlled study,
morphine produced a slow onset (6 hours) and a long duration of perineal
analgesia (5–6 hours) [34]. No changes in heart rate, arterial blood pressure,
nor body temperature were recorded, nor was there any motor impairment
or CNS excitation [35]. Sedation, head ptosis, and perineal skin wheals were
seen [34,35,40].

Butorphanol
Butorphanol is the most common Kappa opioid agonist used systemi-
cally in horses. For caudal epidural analgesia, butorphanol combined with
lidocaine has been shown to improve quality of analgesia and prolonged
duration in horses compared to lidocaine alone [9,14]. In the authorsÕ ex-
perience, butorphanol does not produce analgesia when used alone in clini-
cal cases. In a controlled study the authors showed that butorphanol at
76 E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

0.08 mg/kg, given epidurally, produced no analgesic effect in horses [34].


Similarly, in another study, butorphanol at 0.05 mg/kg, given epidurally
to anesthetized horses did not change the MAC value of halothane [11].

U50488H
U50488H is a pure Kappa opioid agonist which has been shown to pro-
duce no CNS excitatory effects in horses when administered systemically
[23]. In a study in horses, U50488H, at 0.08 mg/kg, produced no analgesia
when given into the caudal epidural space [34].

Alfentanil, fentanyl
Highly lipid soluble Mu opioids such as alfentanil and fentanyl are
rapidly transferred from the epidural space to the subarachnoid space and
to plasma [8,42]. Cephalad movement of lipid-soluble opioids is limited by
uptake into the spinal cord after transferring into the subarachnoid space
[53]. In a controlled study in horses alfentanil at 0.02 mg/kg given into the
caudal epidural space produced a measurable but insignificant analgesic
effect in the perineal and sacral dermatomes [34]. We believe that the reason
why alfentanil produces an increase in the threshold for the noxious stimuli
only over the perineal and sacral regions and not over the lumbar and thor-
acic areas is due to its higher lipid solubility when compared to tramadol
and morphine. The epidural administration of highly lipophilic opioids
should be done immediately adjacent to spinal cord segmental binding sites
to improve selectivity of spinal analgesia [42]. This lack of epidural analgesic
effect observed with kappa opioid agonists and lipophilic mu agonists, such
as alfentanil, could be related to the number and distribution of opioid
receptors in the spinal cord in horses and to the high lipid solubility leading
to a rapid systemic absorption.

Meperidine
A study in mares has shown that meperidine holds promise as a suitable
opioid for epidural adminstration in horses [52]. The effects of meperidine in
the mares; perineal analgesia, decreased tail muscle and anal sphincter tone,
were thought to resemble a local anesthetic action, rather the more typical
effects seen with the opioids [52]. There was mild sedation and ataxia and
no measurable cardiorespiratory side-effects seen in any mares [52].

Tramadol
Tramadol is a synthetic 4-phenyl-piperidine analgesic drug, an analogue
of codeine, with both opioid and non-opioid mechanisms of action [10,38].
At the time of writing, only the oral form is available in the United States.
Epidural administration has demonstrated a fast onset of analgesia in hu-
mans. In a recent study in horses all classes of opioids and tramadol were
comparatively evaluated after epidural administration [34]. Caudal epidural
administration of tramadol showed promise in management of perineal and
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82 77

lumbosacral pain in horses, as did morphine. Regional differences exist in


the intensity and duration of pain relief procedure; tramadol tended to have
a faster onset (30 minutes) than morphine but a shorter duration of analge-
sic action (4 hours) [34].

Clinical applications of epidural opioids and opioid-like analgesics


The clinical use of opioids for epidural analgesia in horses can be recom-
mended for acute and chronic pain control of the rear limb, perineum, tail
and abdominal wall. Time to effect of an epidurally administered opioid is
influenced by the number of molecules retained in the cerebrospinal fluid
and spinal tissue, and by the dissociation kinetics of the drug [8]. Thus there
are differences in onset, spread and duration that can vary with each drug.
Most of the acute and chronic painful situations will involve tissue damage
and will probably benefit of concurrent nonsteroidal anti-inflammatory
(NSAID) systemic treatment (Fig. 2). Segmental analgesia has been repor-
ted after morphine administration in horses which might result in patchy
distribution of analgesia in the perineal and lumbosacral areas [34,40]. Also,
analgesic effects of morphine or ketamine, given into the first intercoccygeal
space of horses, has been shown to spread cranially as far as the mid-
thoracic region and did not affect the forelimb [11,34,40].
Morphine is the only epidural opioid that has shown analgesic effect in
horses when used alone. Although profound analgesia is achieved with mor-
phine, the long onset of action precludes its use alone in acute cases without
combination with faster-acting epidural analgesics such as detomidine, fen-
tanyl, alfentanil or ketamine (Table 1). Tramadol has also been combined
with fentanyl in horses in severe intractable pain (Fig. 2). These combinations
usually produce profound analgesic effects which last for 12 to 24 hours [54].
Placement of an epidural catheter (Fig. 3) allows long-duration pain con-
trol in horses. If epidural catheterization performed at the level of the lum-
bosacral space, the clinician should be careful not to place the catheter in the
subarachnoid space.
In the authorsÕ experience preemptive epidural morphine can be used in
horses submitted to general anesthesia although recovery from anesthesia
may be prolonged where doses >0.1 mg/kg are used. Epidural morphine ad-
ministration in halothane anesthetized horses has been shown to decrease
MAC of halothane in the pelvic limb [11].
For standing surgeries the lack of motor impairment and profound an-
algesia produced by morphine and tramadol suggest that these drugs may
be combined with local anesthetics such as lidocaine to produce long-lasting
surgical anesthesia and prolonged post-operative analgesia without ataxia
or recumbency (Fig. 1). Surgical procedures in the perineal and sacral areas
could be done using this anesthetic/analgesic approach. Laparoscopic
surgeries involving the urogenital tract could also be done with a morphine/
local anesthetic combination.
78 E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82

Dissociative anesthetics
Ketamine
Both epidural and subarachnoid injections of ketamine have been shown
to produce short-duration analgesia in horses [3,16]. Ketamine has been
used alone for caudal epidurals in horses producing 30 to 90 minutes of anal-
gesia, with mild sedation but no cardiorespiratory changes [16]. Superficial
and deep muscle pinpricks were used in the tail, perineal region and upper
hindlimb as noxious stimuli. This study did not evaluate whether the anal-
gesia produced was sufficient for surgery [16]. When epidurally administered
in horses ketamine, at 0.8 and 1.2 mg/kg, reduced the MAC of halothane to
stimulation of the pelvic limb [11].
Ketamine is thought to produce analgesia primarily by its noncompeti-
tive antagonism of NMDA receptors. Thus ketamine is more appropriate
to prevent secondary hyperalgesia which will occur when noxious painful
stimulation activates spinal cord neurons repetitively and intensively in cases
such as chronic laminitis and other orthopedic lesions. High concentration
of ketamine also may produce local anesthetic-like effects blocking Na+
channels [2,13]. Whether epidural ketamine will be useful alone for acute
surgical or traumatic pain in the horses is unknown at this time.
Ketamine may be indicated combined with more potent analgesics such
as morphine. Ketamine has also been studied in combination with xylazine.
Analgesia, tested by pin-prick, was produced in the tail, perineum, anus and
vulva, and extended to the flank in some horses [26]. The effects were longer
in duration than when ketamine was used alone and exceeded 120 minutes.
Mild sedation but no recumbency was produced, and there were significant
decreases in heart and respiratory rates [26].
It is not known at this time if epidurally administered ketamine will pro-
duce CNS stimulation in the awake horse, but clinicians should be aware of
this possibility.

Tiletamine
In an experimental study in horses, tiletamine–zolazepam combination
was injected epidurally in horses at 0.5 and 1.0 mg/kg [36]. No analgesia
was detected in 25% of the studies and only mild analgesia in the others.
No sedation was observed but ataxia was seen in all horses and one horse
showed CNS excitation [36].
Further studies with the dissociative agents, ketamine and tiletamine, are
warranted to evaluate their effectiveness and lack of side-effects, such as
CNS excitement, when used for caudal analgesia in horses.

Conclusions
Pain control and local anesthesia for perineal procedures have become
commonplace in horses with the increased knowledge of the techniques of
E.P. Robinson, C.C. Natalini / Vet Clin Equine 18 (2002) 61–82 79

epidural injection and of the effects of drugs which can be given epidurally.
Combinations of a variety of drugs have allowed the onset and duration of
effects to be more closely tailored to the needs of each horse. Long-duration
pain-control has become a reality with the availability of epidural kits suita-
ble for use in horses, and the knowledge of the effects of new and novel
analgesics. Although caudal epidural anesthesia was traditionally limited
to the sacral and perineal area in horses, to avoid recumbency, the advent
of the use of drugs such as opioids, alpha-2 adrenergic agonists and ketamine
has increased the possibilities for analgesia in more cranial parts of the body.
Many of these drugs which produce undesirable side-effects when given
systemically to horses, can be used epidurally with astoundingly good effect.

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