Veterinary Ophthalmology (2015) 18, 5, 422–428 DOI:10.1111/vop.

12259

Comparison of two bupivacaine delivery methods to control

postoperative pain after enucleation in dogs
Derek W. Y. Chow,* Man Yu Wong† and Hans D. Westermeyer‡
*Veterinary Specialty Hospital, 1/F, 165 Wanchai Road, Wan Chai, Hong Kong; †Department of Mathematics, The Hong Kong University of Science &
Technology, Clear Water Bay, Kowloon, Hong Kong; and ‡NC State College of Veterinary Medicine, 1060 William Moore Drive, North Carolina State
University, Raleigh, NC 27606, USA

Address communications to: Abstract

D. W. Y. Chow
Tel.: (852) 36503000
Fax: (852) 27153490
e-mail: dwychow@gmail.com
Objective To compare the efficacy of a preoperative retrobulbar injection of bupiva-
caine to an intraoperative splash block of bupivacaine in controlling postoperative pain
following enucleation in dogs.
Animals studied Prospective, randomized, double-masked clinical study of 31 client
owned dogs with end-stage ophthalmic disease requiring enucleation.
Procedures Dogs admitted for unilateral enucleation were randomly assigned to receive
bupivacaine 0.5% (1 mL/kg) into the retrobulbar space either via an inferior-temporal
palpebral (ITP) injection preoperatively or an intraoperative splash block. Pain was
assessed prior to pre-anesthetic sedation and at 0, 0.25, 0.5, 1, 2, 4 6, 8, and 24 hours
(H) after extubation by masked observers using a previously described subjective pain
scoring system. Rescue analgesia was initiated if overall pain score was >9 or if the
score in any category at any time point was >3.
Results There were no adverse reactions. One of 15 dogs that received bupivacaine via
a preoperative retrobulbar ITP injection required rescue analgesia. There was no sig-
nificant difference between groups with regard to the need for rescue analgesia or pain
scores at any time point or overall.
Conclusions and Clinical Relevance Pain control using an intraoperative orbital splash
administration of bupivacaine is not significantly different to a preoperative retrobul-
bar injection of bupivacaine.

Key Words: analgesia, bupivacaine, dogs, enucleation, retrobulbar injection, splash

block

at least 8 h in dogs following enucleation, demonstrating a

INTRODUCTION
Enucleation is a common procedure performed by general
practitioners, emergency veterinarians, and veterinary oph-
thalmologists. Pain generated from this procedure has
generally been addressed with the use of systemic periop-
erative opioids and nonsteroidal anti-inflammatory medi-
cations. However, recent publications have demonstrated
that delivery of local anesthetic to the retrobulbar space
prior to enucleation results in significantly less pain after
surgery. Accola et al.1 demonstrated that a retrobulbar
injection using the inferior-temporal palpebral (ITP) tech-
nique achieved the best distribution of local anesthetic
with the shortest time of onset in dogs. Using this tech-
nique, Myrna et al.2 showed that bupivacaine delivered to
the orbit provided acceptable postoperative analgesia for
reduction in observed pain levels after surgery with the
use of a preoperative local anesthetic block.
Retrobulbar injections are not without risk, with a large
retrospective study conducted in humans reporting a com-
plication rate of 0.12% with retrobulbar injections.3 Com-
plication in humans and animals can include brain stem
anesthesia, globe perforation, cardiopulmonary arrest, con-
vulsions, contralateral blindness and retrobulbar hemor-
rhage.1,3–6 To achieve adequate analgesia from a
retrobulbar injection, careful delivery of the analgesic is
important to reach the targeted structures (cranial nerves
III, IV, V, and VI and the ciliary ganglion)1 and avoid
complications. This implies that a good understanding of
the anatomical landmarks necessary for a retrobulbar
injection is important. Understandably, a safer, cheaper,

© 2015 American College of Veterinary Ophthalmologists


or simpler technique would be preferred if similar analge-
sic effects were expected.
In human and veterinary medicine, numerous studies
show the level of analgesia obtained using a splash block is
comparable to that of infiltrative or local nerve blocks.7–10
A splash block refers to the direct application of a local
anesthetic to the site of interest. Splash blocks are inexpen-
sive and technically straightforward.11 The development of
newer continuous delivery devices, depot techniques, and
sustained release devices has also bolstered this form of
analgesia’s popularity in human medicine.12–14
The purpose of this study was to compare the analgesic
efficacy of bupivacaine applied using an ITP retrobulbar
injection prior to enucleation to an intraoperative splash
block in patients undergoing transconjunctival enucleation.
The authors hypothesize that pain control would be simi-
lar regardless of method used.
MATERIALS AND METHODS
This was a prospective, clinical trial involving clinical
cases presented to the clinic with end-stage ocular disease
deemed treatable only with enucleation. This study was
performed in accordance with the ARVO Statement for
the Use of Animals in Ophthalmic and Vision Research.
Written informed consent was obtained from the owner
of each animal. Animals were excluded from this study if
they were aggressive, exhibiting signs suggestive of pain
from the contralateral eye or elsewhere, receiving analge-
sics, undergoing bilateral enucleation or had received anal-
gesic medications 24 h before admission.
All dogs underwent a routine ophthalmic and physical
examination. Ophthalmic examination included slit-lamp
biomicroscopy (Hawkeye, Dioptrix, Lyon, France), indi-
rect ophthalmoscopy (Omega 180; Heine Australia Pty
Ltd, Warringah Mall, NSW, Australia), fluorescein stain-
ing, and in some dogs, when appropriate, Schirmer tear
test I and applanation tonometry (Tono-Penâ XL; Reic-
hert, Depew, NY, USA). Tonometry and Schirmer tear
testing was not performed in cases of obvious globe perfo-
ration, globe rupture, or if the integrity of the globe was
feared to be insufficient to withstand the test. All dogs
were assigned a baseline pain score on admission prior to
administration of analgesic medications. This was based
on a pain scoring system used in previous studies.2,15
(Appendix 1) Diagnostic tests deemed to be necessary to
determine anesthetic risk were also performed. These
included complete blood cell count and serum biochemis-
try for all cases and thoracic radiography, abdominal ultra-
sound, and echocardiography, if indicated.
All dogs were sedated via subcutaneous injection of
0.05 mg/kg acepromazine maleate (Phoenix Pharmaceutical
Inc, St Joseph, MO, USA) and buprenorphine 0.01 mg/kg
(Temgesicâ 0.3 mg/mL; Reckitt Benckiser Pharmaceutical
Ltd, Slough, Berkshire, UK) 60 min prior to induction of
anesthesia. Carprofen (2 mg/kg) (Rimadylâ Pfizer Animal
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 18, 422–428
dog enucleation pain bupivacaine 423
Health, North Ryde, NSW, and Australia) was given subcu-
taneously at the time of sedation. Propofol (1–4 mg/kg)
(Vetofolâ 1.0%; Norbrook Laboratories Ltd, Northhamp-
tonshire, UK) was given intravenously to effect until endo-
tracheal intubation was possible. Dogs were maintained
anesthetized with isoflurane in oxygen. Cefazolin (20 mg/kg)
(1 g/5 mL; China Chemical & Pharmaceutical Co Ltd, Tai-
pei City, Taiwan R.O.C) was given intravenously at the time
of induction and 90 min later. Routine subconjunctival enu-
cleation without orbital prosthesis was carried out by a single
surgeon (DWYC).
The surgeon, observers, and statistician were masked
throughout the study. The hospital pharmacist randomly
assigned the dogs to two groups: the retrobulbar ITP injec-
tion group and splash group. The pharmacist then filled two
identical syringes with either 1 mL/kg of bupivacaine 0.5%
(Marcaine 0.5% AstraZeneca, Hong Kong, China) or an
equal volume of saline and indicated which syringe was to be
administered retrobulbarly via the ITP technique preopera-
tively and which syringe was to be given as a splash block
during surgery. Therefore, each dog underwent a retrobul-
bar ITP injection and a splash block. However, in the retro-
bulbar group, bupivacaine was delivered to the retrobulbar
region via an ITP injection and the splash block delivered
saline to the designated region, while in the splash block
group, saline was delivered into the retrobulbar area by the
ITP injection and bupivacaine was delivered by splash block
to the designated area. The ITP injection was carried out
(by DWYC) after preparing the surgical site, but before
moving the patient into the operating theater. The ITP
technique carried out as previously described.1 Briefly, a 1.5-
inch, 22-gauge spinal needle was bent approximately 10–
20°. The inferior orbital rim was palpated and the needle
positioned at the lateral 1/3 of the eyelid. The needle was
inserted through the eyelid skin and advanced without
changes in direction until a popping sensation indicated the
orbital fascia was pierced. At that point, the needle was
directed slightly nasally and dorsally and advanced 1–2 cm
toward the apex of the orbit. To avoid inadvertent injection
into arterioles or arteries, aspiration was performed to
ensure there was no blood withdrawn before bupivacaine
was injected. The splash block was performed after the globe
was removed from the orbit and hemostasis was achieved.
The entire volume was sprayed into the empty orbit using a
22-g 1.5-inch hypodermic needle attached to a 3-cc syringe
and then allowed to bathe the empty orbit for 30 s by lifting
the wound edges to keep the bupivacaine within the orbit.
The orbit was closed routinely with no attempt to minimize
blotting of the area or keep the bupivacaine within the orbit.
Upon discharge, all dogs received cephalexin (20 mg/kg,
twice daily, PO, for 10 days) (Apo-Cephalex 250 mg; Apo-
tex Inc, Toronto, ON, Canada) and carprofen (2 mg/kg,
twice daily, per os for 5 days) (Rimadylâ 25 mg Tablet;
Pfizer Animal Health, New York, NY, USA).
Pain was assessed at 0, 0.25, 0.5, 1, 2, 6, 8, and 24 H
after extubation using the previously described scoring
424 chow, wong and westermeyer
system by DWYC or an overnight emergency veterinary
surgeon previously trained by DWYC. In all cases, evalua-
tion during the first five time points was performed by
DWYC. Thereafter, one of three previously trained veter-
inarians carried out the evaluation for the remaining time
points for each case. Interobserver variability was not eval-
uated. Rescue analgesia (methadone hydrochloride
0.2 mg/kg IV every 4 h) was initiated if at any time the
overall pain score was greater than 9 or if any category
received a score of more than 3. Data obtained after dogs
received rescue analgesia or additional sedation were
censored from the statistical analysis.
Pain scores between the two groups at each time point
were compared using a Mann–Whitney U-test. The over-
all P-value was calculated by Fisher’s method. The differ-
ences between pain scores at each time point after
extubation and those at extubation were evaluated using a
Wilcoxon signed-rank test with a Bonferroni correction
for multiple comparisons. Differences between groups
with respect to the number of dogs requiring rescue
therapy were compared using Fischer’s exact test. Signifi-
cance was set as P < 0.05. A post hoc power analysis was
performed assuming the null hypothesis with respect to
the number of dogs requiring rescue analgesia in each
group.
RESULTS
A total of 31 dogs (15 in the retrobulbar ITP injection
group and 16 in the splash group) were included in this
study. Reasons for enucleation included 12 dogs with non-
visual and nonsalvageable corneal perforation, nine dogs
with chronic uncontrolled glaucoma, three dogs with kera-
tomalacia in a nonvisual eye, three dogs with intraocular
neoplasia, two dogs with globe rupture, one dog with
nonresectable corneal tumor, and one dog with endoph-
thalmitis. There were 6 Shih Tzu, 4 Pekingese, 3 Pug, 2
American Cocker Spaniel, 2 Corgi, 2 English Cocker
Spaniel, 2 Miniature Schnauzer, 2 Pomeranian, 2 York-
shire Terrier, 1 Beagle, 1 Boston Terrier, 1 Cavalier King
Charles Spaniel, 1 English Bulldog, 1 Golden Retriever,
and 1 mixed-breed dog. Immediately after extubation, a
dog from the retrobulbar ITP injection group began
thrashing, lunging, and vocalizing loudly. This behavior
resulted in a cumulative pain score of 18, requiring rescue
analgesia. However, the behavior was so severe that the
rescue protocol was deemed insufficient to prevent self-
trauma and a clinical judgment to give medetomidine
(0.01 mg/kg, IV) (Domitorâ 1 mg/mL; Pfizer Animal
Health, West Ryde, NSW, Australia) instead was made.
Pain scores from time points after administering mede-
tomidine were censored from the analysis. There were no
other instances in which the cumulative or individual cate-
gory scores warranted rescue analgesia in either group.
Differences between groups were not significant with
respect to gender (P = 0.6916) or age (P = 0.9397).
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 18, 422–428
Differences between groups with respect to breed were
not calculated due to the small number of dogs within
each breed. There were no significant differences in med-
ian pain scores between the two groups at admission or
any time point thereafter (overall P = 0.1948). In the
splash block group, median pain scores at all time points
after extubation were significantly higher (P < 0.0028)
than median pain scores at extubation. In the retrobulbar
group, median pain scores at all time points were not sig-
nificantly higher than median pain scores at extubation
(P > 0.05/8), Fig. 1. There was no significant difference in
the number of dogs requiring rescue analgesia between
the two groups (P = 0.4839). The post hoc power analysis
in this study revealed a power of 0.86.
DISCUSSION
The present study did not detect any significant clinical
differences in pain control after enucleation between deliv-
ery of bupivacaine via a preoperative retrobulbar ITP
injection and an intraoperative splash block to the orbit.
This study was designed to compare the efficacy of two
different bupivacaine delivery methods in controlling post-
operative pain following enucleation. This study did not
have a negative control, because we instead relied on the
bupivacaine efficacy established by Myrna et al.2 As both
groups in the current study received local anesthesia, the
number of dogs requiring rescue therapy was greatly
reduced compared to the study by Myrna et al., which
used a saline negative control. The results of the current
study are similar to a recently published study with a very
similar design.16 Ploog et al. compared the efficacy of a
preoperative ITP injection of lidocaine and bupivacaine to
intraoperative placement of a lidocaine and bupivacaine
soaked gelatin hemostatic sponge. They also failed to
detect any differences between groups with respect to pain
scores or need for rescue analgesia following enucleation.16
Considering the results of the current study were similar
to Ploog et al.’s in terms of pain control, it is unlikely that
a gelatin hemostatic sponge is needed in order for the
local analgesic to be effective within the orbit. Simply
instilling the anesthetic onto the tissue and maintaining at
least 30 s of contact time appears to be sufficient.
A notable difference between the current study and stud-
ies by Myrna et al. and Ploog et al. was the use of bupr-
enorphine instead of hydromorphone2,16 as a preoperative
opioid. The authors of the current study used buprenor-
phine because it was the opioid most familiar to them and
the one they were most comfortable using at the time. Hy-
dromorphone has a higher analgesic potency but a shorter
duration of action compared to buprenorphine.17 It could
have been expected that due to the use of an opioid with a
lower anesthetic potency, higher pain scores would have
been recorded resulting in more dogs needing rescue anal-
gesia. However, this was not the case as results of the cur-
rent study were very similar to those of Ploog et al.16 The
 dog enucleation pain bupivacaine 425

Figure 1. Box-and-whisker plot of pain scores before enucleation and sedation (baseline), immediately upon extubation following enucleation
(Time = 0) and after extubation in dogs receiving either a preoperative retrobulbar injection or an intraoperative splash block of 0.5%
bupivacaine (1 mL/kg). The center of the box represents the median pain score, the outer edges of the box represent the 25th and 75th
percentiles, and the whiskers represent the 10th and 90th percentiles. Values outside the 10 and 90 percentiles are denoted by (•).

current study also mirrored Ploog et al.16 in that pain
scores in the splash block group were lowest immediately
after extubation and tended to rise with time. Possible
explanations for this rise in pain scores include spilling dur-
ing splash delivery leading to a reduction in bupivacaine
available for effective analgesia, incomplete distribution of
the bupivacaine to all sensory nerves in the surgical area, or
increased variability in the pain scores associated with the
retrobulbar ITP injection leading to an inability to detect a
true rise in pain scores in the retrobulbar ITP injection
group. Even though the median pain scores at time 0H are
the same for both groups, the range for the retrobulbar
ITP injection group was significantly higher. For all the
time points after time 0H, except for the 0.25H time point,
the median scores at all time points were identical for both
groups. Additionally, the range of values at each time point
(except time 4H and 6H) was wider for the retrobulbar
ITP injection group compared to the splash block group
(Fig. 1). Furthermore, it is possible that the variability of
the values in the retrobulbar ITP injection group obscures
a rise in pain scores over time. The increased variability
seen in the pain scores for the retrobulbar injection group
could be related to inherent variability associated with this
technique. Alternatively, it could be associated with varia-
tions in the delivery method created by the person adminis-
tering the injection. One person administered all the
injections throughout this study, minimizing variations in
the injection technique used. However, there was a wide
variety of skull anatomies represented in the dogs of this
study and it is possible that this significantly affected the
delivery site of the local anesthetic, resulting in variations
in analgesic effect.
One dog in the retrobulbar group started thrashing and
vocalizing upon extubation. Even though it is uncertain
whether the vocalizing and thrashing behavior exhibited
by this dog was a response to pain or signs of dysphoria,18
this dog was considered to have received rescue therapy
and subsequent data were censored from the analysis. In
people, dysphoria has been described as a feeling of
unpleasantness where the patient will act against the envi-
ronment.19 The distinction between pain and dysphoria
can be difficult because the two conditions can occur con-
currently.20 Animals that are in pain can be distracted
temporarily by interaction or handling and introduction
or redosing of opioids will result in resolution of the
behavior. On the contrary, administration of opioids or
attempts to distract dysphoric animals will not resolve the
behavior.20 Additionally, administration or redosing of
opioids in animals exhibiting dysphoria may exacerbate
the behavior. Tranquilizers (such as acepromazine), seda-
tives (such as medetomidine), or opioid antagonists can be
used to ameliorate dysphoric behaviors.18,21–23
The uncertainty associated with categorizing the behav-
ior of the dog that was vocalizing and thrashing immedi-
ately after extubation highlights the difficulty of assessing
pain in companion animals. Currently, there is no objec-
tive way to measure pain in companion animals. The sub-
jective pain scoring system used in this study, a previously
validated2,15 numerical rating scale, has been shown to be
more sensitive than a simple descriptive scale and easier to
use than a visual analogue scale.24,25 The simplicity of this
scoring system may result in low interobserver variability.
However, this variability was not measured in this study
and constitutes a weakness of this study. Cardinal signs or

© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 18, 422–428

426 chow, wong and westermeyer
objective measurements such as heart rate and respiratory
rate have not shown significant correlation to pain lev-
els16,26,27 and thus were not measured.
Bupivacaine was used instead of lidocaine or a combina-
tion of bupivacaine and lidocaine in the present study
because bupivacaine has an analgesic effect at least three
times more potent than lidocaine28 and remains in the
infiltrated tissue for at least 5 h longer than lidocaine.
Even though the onset time of bupivacaine (15 min) is
slower than lidocaine,29 two separate studies have demon-
strated that the onset time for a lidocaine and bupivacaine
mixture was not different to that of bupivacaine alone.30,31
Thus, there appears to be no benefit from using a combi-
nation of lidocaine and bupivacaine and it may be associ-
ated with added cost and a theoretical increase in adverse
drug reactions. In this study, the time from administration
of the retrobulbar injection to the first surgical incision
was approximately 10–15 min. Therefore, enough time
was allowed for bupivacaine to achieve the desired analge-
sic effect at the enucleation site.
Painful stimuli are transmitted via C-fibers and result in
activation of N-methyl-D-aspartate receptors (NMDA) in
the central nervous system. Once NMDA receptors are
activated, they will become sensitive to glutamate and
more sensitive to pain. This results in subsequent sub-
threshold pain stimuli, minor tissue injury, or surgical
incisions resulting in an exaggerated response. This is
known as the windup effect.32 In theory, the delivery of
the bupivacaine via a preoperative retrobulbar ITP injec-
tion should have blocked all nociception prior to the first
surgical incision. As the bupivacaine was introduced after
surgical trauma to the tissue in the splash block group,
there is the possibility of windup resulting in increased
pain sensation in that group. Opioids are known to sup-
press windup,32 and the use of buprenorphine in this study
may have helped blunt that effect. Even though there was
no statistical difference detected between the two delivery
methods at any time point, the pain scores increased after
extubation for the splash block group, while in the retro-
bulbar ITP injection group, pain scores did not increase.
This may represent a dampening of the windup effect in
the retrobulbar ITP injection group. Alternatively, it may
represent a difference in the efficacy of the delivery
method itself, as opposed to the timing of the delivery.
The fact that no difference between groups was detected
could also represent low sensitivity of the pain scoring sys-
tem itself or increased variability in the retrobulbar ITP
injection group’s pain scores as previously discussed.
None of the dogs developed any adverse effects from
the retrobulbar ITP injection. However, if proper tech-
nique is not used, retrobulbar ITP injections can lead to
serious complications, including cardiopulmonary arrest,
convulsion, blindness in the contralateral eye, loss of con-
sciousness, apnea, depression, and retrobulbar hemor-
rhage.4,5,33,34 Two mechanisms have been proposed to
explain how local anesthetics can be delivered to the brain
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 18, 422–428
via a retrobulbar ITP injection. One mechanism is
inadvertent delivery of the local anesthetic medication
intra-arterially, such as into the ophthalmic artery. As the
injection is delivered, anesthetic is driven into the internal
carotid artery in a retrograde fashion. Once in the carotid
artery, antegrade flow delivers the medication to the
brain.33,35 However, cannulation of the artery is quite
difficult and if the artery is perforated, blood should be
observed at aspiration or evidence of hemorrhage pres-
ent.34 Alternatively, the needle can perforate the menin-
geal sheath surrounding the optic nerve. The local
anesthetic can then gain access to the subarachnoid space
and the cerebrospinal fluid.34 A recent study in humans
reviewed and described extraconal delivery of local anes-
thetic to the retrobulbar region.36 Extraconal delivery of
local anesthetic minimizes the risk of intra-arterial or int-
rameningeal administration of local anesthetic. In that
study, 3–4 times more local anesthetic was required to
achieve analgesia and akinesia compared to intraconal
delivery.36 Depending on the penetration and diffusion of
the local anesthetic, it may be ineffective or the onset time
may be prolonged when delivered extraconally.36
The use of multiple observers is a clear limitation in the
present study. We tried to reduce this limitation using
one observer for at least the initial five time points and
also one observer per animal at subsequent time points.
However, it is still possible that interobserver variability
led to a decreased ability to detect differences between
groups. The lack of a negative control should also be con-
sidered a limitation of this study. Considering the unam-
biguous results of the study by Myrna et al.,2 showing that
a preoperative retrobulbar ITP injection of bupivacaine
resulted in superior pain control compared to a saline con-
trol, it did not seem appropriate to submit animals to a
pain control protocol that had been documented as infe-
rior. Thus, our goal was to differentiate between two dif-
ferent bupivacaine delivery methods and not focus on
whether bupivacaine administered via a retrobulbar ITP
injection was effective.
Our results show that using a technically simpler intra-
operative splash block does not result in any clinically sig-
nificant differences in postoperative pain compared to a
preoperative retrobulbar ITP injection of local anesthetic.
The effectiveness and simplicity of the introduction of
0.5% bupivacaine via a splash block technique means that
effective analgesia for enucleation can even be achieved in
patients with a deformed retrobulbar anatomy, such as
those from motor vehicle accident or osteolysis of the
facial bone from neoplasia or infection. A splash block is
inexpensive and can be performed easily by nonspecialist
veterinarians. Further studies could include evaluation of
different preoperative opioids and their effect on postoper-
ative pain, evaluation of other local anesthetics such as eti-
docaine or mepivacaine, and evaluation of perioperative
pain control protocols in surgeries where the depth of
anesthesia is standardized across all subjects.

ACKNOWLEDGEMENTS
The authors would like to thank Dr. Anthony Hollis,
Dr. Karen Ng, and Dr. Glen McIntosh for their help in
data collection through the nighttime period.
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428 chow, wong and westermeyer

Appendix 1

Pain scoring system for dogs undergoing enucleation

Observation Score Criteria

Comfort 0 Dog asleep or calm

1 Awake, interested in surroundings
2 Mild agitation or depressed, uninterested in surroundings
3 Moderate agitation, restless, and uncomfortable
4 Extremely agitated and thrashing
Movement 0 Quiet
1 1–2 position changes/min
2 2–6 position changes/min
3 Continuous position changes
Appearance 0 Too sedate to evaluate
1 Normal
2 Allows, but then moves away when operated eye touched
3 Will not allow operated eye to be touched
4 Will not allow head to be touched
Behavior (unprovoked) 0 Too sedate to evaluate Normal
1 Minor changes
2 Moderately abnormal (less mobile or alert than normal;
3 Unaware of surroundings or very restless)
4 Markedly abnormal (very restless, vocalization, self-mutilation, grunting,
or facing back of cage)
Vocalization 0 Quiet
1 Crying, but responds to quiet voice and stroking
2 Intermittent crying, no response to quiet voice and stroking
3 Constant crying (unusual for this individual animal; no response to stroking or voice)

© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 18, 422–428