l

1. PAPER
Effects of postoperative ketamine
infusion on pain control and
feeding behaviour in bitches
undergoing mastectomy
OBJECTIVES: To determine if ketamine administered to bitches at
the end of a mastectomy, followed by a six-hour constant
rate infusion (CRI), improved postoperative opioid analgesia and
feeding behaviour.
METHODS: The bitches were randomised into three groups: the
placebo group received 009 ml/kg isotonic saline intravenously
followed by a six-hour CRI of 0
5 ml/kg/hour, the low-dose
ketamine received 150 mg/kg ketamine intravenously followed by
a six-hour CRI of 2 mg/kg/minute and the high-dose ketamine group
received 700 mg/kg ketamine intravenously followed by a six-hour
CRI of 10 mg/kg/minute. Any additional opioids given were
recorded at the time of extubation and at intervals after extubation.
Food intake was evaluated eight (T8) and 20 (T20) hours after
extubation by measuring the per cent coverage of basal energy
requirements (BER).
RESULTS: No significant difference was observed for opioid
requirements between the three groups. The mean percentages of
BER coverage did not differ significantly at T8 but the difference
between the high-dose and low-dose ketamine groups (P50014),
and the high-dose ketamine and placebo groups (P50
038) was
significant at T20.
CLINICAL SIGNIFICANCE: This study demonstrated that 700 mg/kg
ketamine given intravenously postoperatively followed by a
six-hour ketamine CRI of 10 mg/kg/minute improved patient
feeding behaviour.
S. SARRAU, J. JOURDAN,
F. DUPUIS-SOYRIS AND P. VERWAERDE
Journal of Small Animal Practice (2007)
48, 670–676
DOI: 10.1111/j.1748-5827.2007.00362.x
INTRODUCTION
Postoperative pain has morbid effects in
small animals (Gaynor 1999) as in humans,
and can compromise recovery. It increases
significantly the rate of postoperative com-
plications (infectious complications, car-
diovascular failure) (Yeager and others
1987), which may possibly worsen the
outcome. Therefore, provision of analge-
sia is essential to ensure a rapid and suc-
cessful outcome after surgical treatment.
Tissue damage during surgery results in
the production of inflammatory mediators
that decrease the threshold of nociceptors
(Lundeberg 1995, Sidall and Cousins
1995). The increased peripheral nerve
stimulation activates N-methyl D-aspar-
tate receptors (NMDA) in the dorsal horn
of the spinal cord (Sidall and Cousins
1995) which facilitates nociceptive trans-
mission to the central nervous system lead-
ing to central sensitisation to pain (Haley
and others 1990, Woolf and Thompson
1991, Ren and others 1992). This phe-
nomenon, known as the wind-up effect,
is clinically expressed by hyperalgesia
(increased sensitivity to painful stimuli)
and allodynia (pain perception from
non-painful stimuli) (Lundeberg 1995).
The NMDA receptor is suspected to be
the main factor in central sensitisation.
It also plays a role in opioid tolerance
(decreased pain levels with increasing
opioid doses) (Mao and others 1995)
and opioid hyperalgesia. Research to
improve pain management and pain pre-
vention has focused on this receptor, con-
sidering its great role in pain perception.
Ketamine is a non-competitive NMDA
antagonist known to suppress central sen-
sitisation in humans (Stubhaug and others
1997). Numerous clinical studies have
been performed to evaluate its potential
synergistic effects with opioids in postop-
erative pain control. Ketamine seems to
reduce postoperative opioid consumption
while maintaining good or even better
analgesia than opioids alone (Fu and
others 1997, Guillou and others 2003,
Lahtinen and others 2004). This phenom-
enon known as an opioid-sparing effect
can be advantageous because of the side
effects of high doses or repeated adminis-
tration of opioids (including respiratory
depression, constipation, dysphoria and
urine retention) (Reisine and Pasternak
National Veterinary School of Toulouse,
Anaesthesia and Critical Care Unit, 23, Chemin
des Capelles, 31076 Toulouse Cedex, France
670 Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association

2. 1996). Unfortunately, the demonstration
of an opioid-sparing effect of ketamine
has not been consistent in all studies
(McCartney and others 2004).
In veterinary medicine, a report showed
that ketamine used alone at less than
anaesthetic doses administered intramus-
cularly produced analgesia (Slingsby and
Waterman-Pearson 2000). Only one clin-
ical study reported ketamine use in associ-
ation with opioids (Wagner and others
2002): it was demonstrated that ketamine
constant rate infusion (CRI) from the
beginning of surgery until 18 hours after
surgery in patients undergoing forelimb
amputation improved pain control at 12
and 18 hours after surgery and improved
the postoperative comfort of the dogs, but
it failed to show an opioid-sparing effect.
As Wagner and others (2002) found in
dogs, most of the protocols used in
humans that show an opioid-sparing effect
or better postoperative pain control using
ketamine follow a strategy of pre-emptive
analgesia: that is, administration of ket-
amine preoperatively to prevent postoper-
ative pain associated with surgery. But
Arendt-Nielsen and others (1995) postu-
lated that ketamine cannot act as a pre-
emptive analgesic agent because it can
only inhibit NMDA receptor activity
when its ion channel has been opened by
nociceptive stimuli. In view of the find-
ings of Arendt-Nielsen and others (1995),
and despite benefits of pre-emptive anal-
gesia shown by Wagner and others
(2002), we chose to study the effect of
postoperative ketamine administration on
postoperative pain control. To the authors’
knowledge, this is the first study of its
kind.
The aim of the study of bitches under-
going mastectomy was to determine if
a single bolus of ketamine at the end of
the surgical procedure, followed by a six-
hour CRI, improved postoperative opioid
analgesia, influenced postoperative feed-
ing behaviour and allowed an opioid-spar-
ing effect to occur.
MATERIALS AND METHODS
Twenty-seven bitches from a wide variety
of breeds were included in this study. Each
animal was admitted to the authors’ hos-
pital for mastectomy of at least two mam-
mary glands. The inclusion criteria were
American Society of Anaesthesiologists
physical status of III or less, no arterial
hypertension or congestive heart failure,
no treated hypothyroidism or history of
epilepsy and no analgesic therapy with
non-steroidal anti-inflammatory drugs or
corticoids for two weeks before surgery.
Owner consent was obtained before the
surgical procedure. Preanaesthetic bio-
chemical analyses (creatinine and protein)
were performed. Dogs with hypercreatini-
naemia (creatinine level$133 lmol/l)
were excluded from the study.
After a baseline clinical evaluation, the
bitches were anaesthetised according to
a standardised protocol. All bitches were
premedicated with 005 mg/kg acepro-
mazine (Vetranquil 05 per cent; CEVA
Santé Animale) intramuscularly and 02
mg/kg morphine chlorhydrate (Morphine
Meram 1 per cent; Cooper) intramus-
cularly 20 minutes before induction.
General anaesthesia was induced with
4 mg/kg propofol (Rapinovet; Shering-
Plough) intravenously via a venous cathe-
ter and maintained with isoflurane (Forene;
Abbott) in 100 per cent oxygen. All bitches
received 09 per cent sodium chloride at
a rate of 10 ml/kg/hour intravenously
throughout anaesthesia and surgery. Mor-
phine chlorhydrate was not administered
during anaesthesia. All surgical procedures
lasting for more than four hours (the mean
action time of morphine chlorhydrate
[Hansen 1992]) were excluded from the
study.
At the end of surgery, the bitches were
randomised into three groups. Group 1
was designated the placebo group and
the dogs received a bolus of 01 mg/kg
morphine chlorhydrate intravenously and
a bolus of 009 ml/kg isotonic saline intra-
venously at the extubation, followed by
a six-hour CRI of isotonic saline at a dose
of 05 ml/kg/hour. The bitches in group
2, or the low-dose ketamine group, at
extubation received a bolus of 01 mg/
kg morphine chlorhydrate intravenously
and a bolus of 150 lg/kg ketamine (Clor-
ketam 1000; Vétoquinol) intravenously
diluted in isotonic saline to attain a total
volume of 009 ml/kg, followed by a six-
hour CRI of ketamine at a dose of 2 lg/
kg/minute, diluted in isotonic saline to
permit a rate of 05 ml/kg/hour. The
patients in group 3, or the high-dose ket-
amine group, at extubation received
a bolus of 01 mg/kg morphine chlorhy-
drate intravenously and a bolus of 700 lg/
kg ketamine intravenously diluted in iso-
tonic saline to attain a total volume of
009 ml/kg, followed by a six-hour CRI
of ketamine at a dose of 10 lg/kg/minute
diluted in isotonic saline to obtain a rate
of 05 ml/kg/hour. Syringes of 09 per
cent sodium chloride, low-dose ketamine
or high-dose ketamine were prepared by
one of the investigators (S. S.). This tech-
nical assistant had no further contact with
the patient or the clinical procedure. The
sole investigator (F. D.-S.) involved in
patient management and data collection
did not know to which group the patient
was assigned.
Pain score, sedation score and addi-
tional doses of morphine chlorhydrate
were recorded at the time of extubation
(T0) and one, two, four, six, eight and
20 hours after extubation by the same per-
son throughout the study. Postoperative
recovery was evaluated at eight and
20 hours after extubation.
Pain scoring
Pain was first assessed using a French mul-
tiparametric scoring scale. The French
Veterinary Association for Anaesthesiol-
ogy and Analgesia (4A VET) pain scoring
scale, shown in Fig 1, was compiled in
2001 by the 4A VET, based on subjec-
tive pain evaluation, clinical parameters
and behavioural criteria (Verwaerde and
Estrade 2005). Pain scores ranged from
0 to 18 and the higher the score, the
greater the pain. Pain was assessed sec-
ondly by a visual analogue scale (VAS)
(0=no pain and 100=worst possible pain)
taking into account only the subjective feel
of the observer. The investigator involved
in patient management and pain scoring
had become familiar with the 4A VET
multiparametric scoring scale and the
VAS before starting the study.
Morphine chlorhydrate
requirements
Additional doses of morphine chlorhy-
drate were administered during the post-
operative period if the pain score was
above six (that is more than slight pain)
Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association 671
Effects of postoperative ketamine infusion on pain control and feeding behaviour

3. according to the 4A VET scoring scale. If
there was at any time a distortion between
the subjective feel of the observer (VAS
pain score .5) and the 4A VET pain score
(,6), the VAS pain score served as a cut-
off for additional morphine administra-
tion. Accurate morphine chlorhydrate
requirements were obtained by admin-
istering a repeat intravenous bolus of
01 mg/kg morphine chlorhydrate every
10 minutes. Total cumulative doses of
morphine chlorhydrate administered dur-
ing the study and the time to first rescue
injection were recorded.
Feeding behaviour
Dysorexia is one of the clinical signs of
pain (Bistner and others 2000), and post-
operative pain control was completed with
an assessment of feeding behaviour at
eight (T8) and 20 hours (T20) after extu-
bation. Six hours after extubation, bitches
were fed moistened food (WALTHAM
Canine Sensitivity Control, Chicken with
Rice, 129 kcal/g) ad libitum. The time
of spontaneous refeeding was recorded.
Spontaneous food intake was calculated
at T8 and T20 by measuring the difference
between the quantity (g) of food given and
theamountoffoodnoteatenbythedog(g).
The metabolisable energy intake (MEI
[kcal]=food intake [g]129 [kcal/g]) and
basal nutritional energy requirements
(BER [kcal/day]=k70weight [kg]075
with k=15) were then calculated (Mauldin
and Davidson 2003).
Sedation scoring
At each time of pain assessment, sedation
was scored according to a scale defined by
Young and others (1990) that ranged from
0 to 19. A high score indicated that the
patient was asleep and a low score that
the patient was awake.
Side effects
Any side effects of analgesic drugs during
the first six hours after extubation, such as
bradycardia (#50 per cent of the baseline
heart rate), drooling, emesis, muscular
tremors or mydriasis, were recorded.
Statistical analysis
A statistical analysis was performed using
Statview F4.5 software (Abacus Concepts).
Comparisons within each group were ana-
lysed using a one-way analysis of variance
(ANOVA) for repeated measures and fol-
lowed when required by a Bonferroni-
Dunett test. The statistical analysis of
group characteristics was performed using
an ANOVA, followed by a Scheffe test
for multiple comparisons. A statistical anal-
ysis of the treatment effect was performed
using an ANOVA, followed by a Bonfer-
roni-Dunett post hoc test. The results are
depicted as mean (sem). A P value less than
005 was considered significant.
RESULTS
Twenty-sevenbitchesaged between55 and
155 years were included in the present
study.Accordingtotherandomisationtable,
10 were assigned to group 1, the placebo
group; eight were in group 2, the low-dose
ketamine group; and nine were in group
3, the high-dose ketamine group. No signi-
ficant difference was observed between the
three groups for age, weight, extent of mas-
tectomy, duration of surgical procedure or
biochemichal profiles (Table 1).
Postoperative pain evaluation
Pain intensity evaluated by VAS scoring
decreased gradually from the time of
Subjective pain score: no pain....................................................................................................0
................................................................................................................1
................................................................................................................2
worst possible pain.................................................................................3
General attitude: Among the following clinical signs: respiratory modifications, vocalisation,
ventrally incurved back,avoidance posture, weakness or excitation, anorexia,
bite or lick or look at the surgical wound, how many are present?
no sign present........................................................................................0
1 sign present..........................................................................................1
2 to 4 signs present.................................................................................2
more than 4 signs present...................................................... ................3
Interactive behaviour: response to strokes and calls.................................................................0
timid response…....................................................................................1
no immediate response..........................................................................2
no or aggressive response........................................................... ..........3
Heart rate increasing: 10%......................................................................................................0
11 to 30%...............................................................................................1
31 to 50%...............................................................................................2
50%......................................................................................................3
Surgical wound palpation:
no visible or audible reaction after 4 palpations....................................0
visible or audible reaction at the 4th palpation......................................1
visible or audible reaction at the 2nd or 3rd palpation...........................2
visible or audible reaction at the 1st palpation or impossible................3
Intensity of the reaction:
no reaction…………………………………………………………….0
slight reaction, attempt to withdraw…………….…………………….1
turns the head, vocal response…...……….…………………………...2
attempt to flee or to aggress...………….………………..……………3
TOTAL SCORE
1 to 5
6 to 10
11 to 18
slight pain
moderate pain
severe pain
FIG 1. 4A VET multiparametric scoring scale
Table 1. Characteristics of the different groups studied (mean6sem)
n Age (years) Weight (kg) Duration of surgical
procedure (minutes)
Extent of
mastectomy (%)*
Plasma
creatinine (mmol/l)
Plasma
protein (g/l)
Placebo 10 101606 109622 11386106 860695 670630 720620
Low-dose KET 8 92605 93621 12086154 850698 656636 717610
High-dose KET 9 89606 128618 1496148 8676107 786655 721621
KET Ketamine
*Percentage of mammary tissue excised, an entire mammary gland chain corresponding to a 100 per cent mastectomy. One-way analysis of variance followed by a Scheffe
post hoc test
672 Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association
S. Sarrau and others

4. extubation to the last pain scoring 20
hours after extubation in all three groups
(Fig 2). No significant difference between
groups was observed at any time during
the clinical evaluation. These observations
were consistent with the 4A VET pain
score evaluation (Fig 3).
Morphine chlorhydrate
requirements
Ketamine infused at a low or high dose
failed to significantly decrease postopera-
tive morphine chlorhydrate requirements
when compared with the placebo group
(Fig 4). The results show that approxi-
mately 80 per cent of the total cumulative
doses of morphine chlorhydrate used to
manage postoperative pain were admi-
nistered during the first four hours after
surgery.
Feeding behaviour
The percentage of BER coverage was cal-
culated eight (T8) and 20 (T20) hours
after extubation (Table 2). At T8, bitches
in the high-dose ketamine group had
a higher per cent coverage of BER than
those in the placebo group (P=0067).
The use of low-dose ketamine failed to
induce a significant difference with the
placebo group. At T20, a significant dif-
ference was recorded between the high-
dose ketamine group and the other two
groups.
Sedation score
The sedation score, evaluated according
to the scale defined by Young and others
(1990), fell gradually from extubation
to 20 hours after extubation (Fig 5).
No significant difference between seda-
tion scores for the three groups was
observed at any time during the clinical
evaluation.
Side effects
There was no difference in the incidence
of side effects induced by ketamine
(including drooling, mydriasis and mus-
cular tremor) or morphine chlorhydrate
(including drooling, emesis and bradycar-
dia) between the groups. Drooling, which
could be considered a ketamine or mor-
phine chlorhydrate side effect when asso-
ciated with nausea, was observed most
often in the high-dose ketamine group.
No emesis was observed during the post-
operative period. One dog in the placebo
group presented severe bradycardia, re-
quiring atropine treatment.
DISCUSSION
The results of the current study suggest
that administering a single, high dose
(700 lg/kg) of intravenous ketamine after
mastectomy in bitches, followed by a six-
hour CRI of ketamine at a dose of 10 lg/
kg/minute enhanced food intake but
failed to reduce the need for morphine
chlorhydrate postoperatively.
Ketamine is a non-specific NMDA
receptor antagonist, commonly used to
induce anaesthesia, which may exhibit
synergistic analgesic properties with opi-
oids at sub-anaesthetic doses in humans
(Kohrs and Durieux 1998). These proper-
ties have been widely studied in humans
over the past 15 years. In a qualitative sys-
tematic review of the role of NMDA
antagonists in analgesia (McCartney and
others 2004), only 58 per cent of the 24
articles investigating the effect of perioper-
ative ketamine administration (before,
during or at the end of surgery) succeeded
in demonstrating an analgesic effect based
on a reduction of pain scores, analgesic
drugs consumption or both. This explains
why there is still doubt about the demon-
strable efficacy of ketamine to produce
analgesia.
Ketamine has been reported to show
potential analgesic efficacy particularly
in patients with extended skin lesions such
as burn wounds (Joubert 1998) or in pa-
tients having undergone extended cutane-
ous surgery (Adam and others 1999).
Therefore, it seemed reasonable to use ket-
amine for management of pain in bitches
undergoing mastectomies.
The decision to use ketamine CRI at
the end of the surgery was based on the
findings of Arendt-Nielsen and others
(1995) who postulated that ketamine can-
not act as a pre-emptive analgesic because
it can only inhibit NMDA receptor activ-
ity when its ion channel has been opened
by nociceptive stimuli.
Asingleintravenousdoseofketaminefol-
lowed by a ketamine CRI was based on the
observations of Slingsby and Waterman-
Pearson (2000) and Wagner and others
(2002). Slingsby and Waterman-Pearson
0
10
20
30
40
50
60
T0 T1 T2 T4 T6 T8 T20
Time after extubation
VAS
pain
score
*
*
*
* *
*
Placebo
Low dose
High dose
FIG 2. Visual analogue scale pain score (mean [sem]) at extubation (T0) and one, two, four,
six, eight and 20 hours after extubation. A one-way analysis of variance was performed for
repeated measures followed by a Bonferroni-Dunett post hoc test using T0 as a control value.
* P,005 when compared with T0 value for the placebo group, n P,005 when compared
with T0 value for the low-dose ketamine group, : P,005 when compared with T0 value
for the high-dose ketamine group
Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association 673
Effects of postoperative ketamine infusion on pain control and feeding behaviour

5. (2000)usedapreoperativeorpostoperative
single dose of 25 mg/kg ketamine intra-
muscularly in female dogs undergoing
ovariohysterectomy. Postoperative analge-
sia was obtained for a short period.
Repeated ketamine administrations were
then suggested to prolong the analgesic
effect, but seemed to increase the incidence
ofpsychomimeticsideeffects.Toovercome
these side effects and extend the duration of
analgesia without repeated ketamine
administrations, the use of a low-dose ket-
amine CRI was proposed in humans
(Owen and others 1987), and studied for
the first time in dogs by Wagner and others
(2002).
The target plasma ketamine concentra-
tions in this CRI context were 150 ng/ml
in humans according to Suzuki and
others (1999) and 500 ng/ml in dogs
according to Wagner and others (2002).
The single intravenous dose and rate of
infusion required to produce these con-
centrations in dogs were mathematically
calculated and based on the pharmacolog-
ical data for ketamine in dogs established
by Henthorn and others (1999) and
Schwieger and others (1991). A single
intravenous dose of 150 lg/kg followed
by a six-hour CRI of 2 lg/kg/minute
was required to reach and maintain a
theoretical plasma ketamine concentra-
tion of 150 ng/ml in dogs. A single intra-
venous dose of 700 lg/kg followed by a
six-hour CRI of 10 lg/kg/minute was re-
quired to reach and maintain a theoretical
plasma ketamine concentration of around
500 ng/ml in dogs.
Ketamine has been reported to exhibit
an opioid-sparing effect in several types of
protocols and surgical procedures in
humans (Adam and others 1999, Dahl
and others 2000, Menigaux and others
2000, Guillou and others 2003, Lahtinen
and others 2004, Subramaniam and others
2004). In the present study, the pain
scores according to the VAS and 4A
VET scales did not differ significantly
between the three groups at any time in
the clinical evaluation. This permitted
a comparison of pain management and
particularly morphine chlorhydrate re-
quirements between the groups. Low-dose
(2 lg/kg/minute) and high-dose (10 lg/
kg/minute) ketamine CRIs failed to pro-
duce opioid-sparing effects, and opioid
requirements did not differ significantly
between the three groups. The same
results were obtained with a ketamine
CRI of 2 lg/kg/minute administered as
early as the start of surgery in dogs by
Wagner and others (2002). This difference
between humans and dogs could be ex-
plained by the fact that in humans, pain
management was self-controlled using opi-
oid pumps (patient-controlled analgesia).
*
*
3
2
1
0
4
5
6
7
8
9
10
Multiparametric
pain
score
T0 T1 T2 T4 T6 T8 T20
Time after extubation
Placebo
Low dose
High dose
FIG 3. 4A VET pain score (mean [sem]) at T0 and one, two, four, six, eight and 20 hours after
extubation. Analysis of variance for repeated measures followed by a Bonferroni-Dunett post hoc
test using T0 as control value. * P,005 when compared with T0 value for the placebo group,
n P,005 when compared with T0 value for the low-dose ketamine group, : P,005 when
compared with T0 value for the high-dose ketamine group
*
* *
*
*
*
* *
*
*
*
* *
*
*
*
* *
*
*
0
0.05
0.1
0.15
0.2
0.25
0.3
Morphine
chlorhydrate
administration
(mg/kg)
T0 T1 T2 T4 T6 T8 T20
Time after extubation
Placebo
Low dose
High dose
FIG 4. Morphine chlorhydrate consumption (mean [sem]) at T0 and one, two, four, six, eight and
20 hours after extubation. Analysis of variance for repeated measures followed by a Bonferroni-
Dunett post hoc test using T0 as control value. * P,005 when compared with T0 value,
n P,005 when compared with T0 value for the low-dose ketamine group, : P,005 when
compared with T0 value for the high-dose ketamine group
674 Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association
S. Sarrau and others

6. This type of self-controlled administration
provided an accurate record of opioid
requirements. However, for animals, pain
assessment was made by an external
observer who judged the level of pain felt
and possibly administered opioids earlier
than a self-administering human would
have. Thus, opioid requirements were
probably more difficult to evaluate. Sec-
ondly, doses in veterinary trials were adap-
ted from human studies, and the optimal
analgesic doses of ketamine would perhaps
be higher than those used in the present
study or by Wagner and others (2002).
Another observation concerned the
total cumulative doses of morphine
chlorhydrate needed in the postoperative
period to manage pain. Approximately
80 per cent of the total morphine chlorhy-
drate requirements was administered
within the first four hours in all three
groups. Perhaps a higher preoperative dose
of morphine chlorhydrate than the one
used in our study may have reduced total
cumulative doses of morphine chlorhy-
drate needed in the immediate postopera-
tive period and would be recommended.
In fact, the main benefit of ketamine
CRI observed in the present study
concerned feeding behaviour which was
evaluated by BER coverage. Age is not
a parameter included in the standard
calculus of BER (Mauldin and Davidson
2003); yet, some reports showed that
age could influence basal metabolic rate
(Mount and Rowell 1960, Fukagawa
and others 1990), so probably BER and
BER coverage estimation. But in our
study, age was not significantly different
between groups; this permitted us to eval-
uate the effect of ketamine CRI on per-
centage of BER coverage in spite of the
potential influence of age on basal meta-
bolic rate. Thus, eight and 20 hours after
extubation, the mean percentage of BER
coverage for bitches in the high-dose
ketamine group was higher than those
for bitches in the placebo and the low-dose
ketamine groups. The differences were sta-
tistically significant only at 20 hours after
extubation (Table 2). Bitches in the high-
dose ketamine group ate significantly
more and earlier than those in the placebo
and the low-dose ketamine groups. Con-
sequently, the results show that only
a high-dose ketamine CRI provided a clin-
ical benefit. An enhancement of postoper-
ative recovery after ketamine CRI was also
described by Wagner and others (2002).
This was not based on feeding behaviour,
as in the present study, but on personality,
demeanour and activity which were signi-
ficantly improved by the third day after
surgery. The enhancement of feeding be-
haviour observed in the current study has
not been described in humans. It cannot
be excluded that the increase in food
intake observed in the high-dose ketamine
group can be linked to a stimulating effect
of ketamine or an increasing metabolic
rate induced by ketamine rather than
improved analgesia or sense of comfort
even if this has not previously been
described.
As the sedation scores did not differ sig-
nificantly between the three groups at any
time during the clinical evaluation, it was
concluded that the use of ketamine CRI at
either a low or high dose did not prolong
recovery from the anaesthesia.
Ketamine use in humans is often asso-
ciated with side effects such as hallucina-
tions, nightmares or visual disturbances.
These effects are difficult to evaluate in
dogs. The frequently described side effects
induced by ketamine in animals are mus-
cular tremor, mydriasis or drooling. The
more commonly described side effects of
morphine chlorhydrate are bradycardia,
emesis or constipation. The only severe
side effect of bradycardia in the current
study was observed in one bitch in which
Table 2. Percentage of BER coverage for each group at T8 and T20 after extubation
(mean6sem)
Group Percentage of the
BER coverage at the
first meal (T8) (%)
Percentage of the
BER coverage at T20 (%)
Placebo 264666 5396117a
Low-dose KET 263689 5196155b
High-dose KET 437634 909656a,b
BER Basal energy requirements, KET Ketamine, a
P=0038, b
P=0014
Analysis of variance followed by a Bonferroni-Dunett post hoc test, significant differences between values are noted ‘‘a’’ and ‘‘b’’
*
*
*
*
*
*
6
4
2
0
8
10
12
14
16
18
Sedation
score
Placebo
Low dose
High dose
T0 T1 T2 T4 T6 T8 T20
Time after extubation
FIG 5. Sedation score (mean [sem]) at T0 and one, two, four, six, eight and 20 hours after
extubation. Analysis of variance for repeated measures followed by a Bonferroni-Dunett post hoc
test using T0 as control value. * P,005 when compared with T0 value, n P,005 when
compared with T0 value for the low-dose ketamine group, : P,005 when compared with
T0 value for the high-dose ketamine group
Journal of Small Animal Practice Vol 48 December 2007 Ó 2007 British Small Animal Veterinary Association 675
Effects of postoperative ketamine infusion on pain control and feeding behaviour

7. pain was solely managed with morphine
chlorhydrate. This shows that the ket-
amine doses investigated seem to be safe
and underlines the importance of finding
analgesic drugs which can act synergisti-
cally with the opioid to reduce the inci-
dence of opioid side effects.
Conclusion
The current study demonstrated that
ketamine use during the postoperative
period in bitches undergoing mastectomy
improved patient feeding behaviour but
with no opioid-sparing effect. The high-
dose ketamine CRI (10 lg/kg/minute)
showed greater efficacy than the low-dose
ketamine CRI (2 lg/kg/minute). A 10 lg/
kg/minute ketamine CRI with morphine
chlorhydrate failed to induce any severe
side effects and appeared to provide a safe
analgesic procedure for managing the
severe pain associated with major cutane-
ous surgery. Further studies should be per-
formed to see whether an opioid-sparing
effect can be induced by NMDA receptor
antagonists.
Acknowledgements
The authors thank Séverine Dumond, the
authors’ nurse, for her valuable help.
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S. Sarrau and others