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RESEARCH ARTICLE Indian Journal of Animal Research, Volume Issue : ()

Effects of Propofol, Ketamine and their Combination (ketofol)

as Total Intravenous Anesthesia (TIVA) on Haematological,
Serum Biochemical and Hormonal Profile in the Surgical
Management of Canine Patients
Basanta Saikia, Kushal Konwar Sarma, Kalyan Sarma1

ABSTRACT
Background: The non-availability of the sophisticated anaesthetic machine and the necessary equipment to administer inhalant
anaesthetic in the field hospitals make their use practically unfeasible for the field veterinarians. Therefore, the present study was
undertaken to evaluate the effect of propofol, ketamine and their combination ‘Ketofol’ as a TIVA on certain haematological, serum
biochemical and hormonal profiles in atropine and xylazine premedicated dogs.
Methods: The study was conducted in eighteen clinical cases of dogs of either sex. The animals were randomly divided into three
groups with six animals in each group. All the three groups were premedicated with Atropine sulphate @ 0.04mg/kg body weight and
xylazine HCl @ 0.5mg/kg body weight intramuscularly. In group-I, propofol @ 5mg/kg body weight, in group-II, ketamine @ 5mg/kg
body weight and in group-III, ketofol @ 4mg/kg body weight was administered intravenously for induction after 15 minutes of pre-
anesthetic administration. Surgical anaesthesia was maintained for 90 minutes in all three groups viz. group-I, group-II and group-III
with propofol @ 2.5mg/kg. b.w., ketamine @ 2.5mg/kg b.wt. and ketofol @ 2mg/kg b.wt. respectively by intermittent bolus injection
(IBI) technique. Haematological, serum biochemical and hormonal profile were evaluated before administration of the anaesthetic
agent (0 minutes) then at 15, 30, 60 and 90 minutes during and after administration of anaesthetic agents.
Result: The study revealed that Hb, PCV and TEC were significantly decreased in all the groups at 60 mints and 30mints respectively.
The biochemical evaluation revealed that blood glucose level was significantly increased in all the groups until the end of the experiment.
BUN and creatinine value was a significant increase in group-I and group-II than group-III at different time intervals up to the end of
the experiment. In all the groups’ alanine aminotransferase (ALT) values significantly increased up to 60th minutes during TIVA
whereas AST value was significantly increased in group-II at 30th and 60th minute of the experiment in compare to group-I and group-
III. A higher level of cortisol values was recorded in group-I animals for the entire period of observation. There were no changes
observed in the case of T 3. Transient variables of haemato-biochemical have been reported following propofol, ketamine and their
combination (ketofol) as total intravenous anaesthesia (TIVA). Thus, it has been concluded that diligent monitorization and electrolyte
support are essential during the period of anaesthesia.

Key words: Dog, Haemato-biochemical, Hormonal profile, Ketamine, Ketofol, Propofol, TIVA.

INTRODUCTION Department of Veterinary Surgery and Radiology, College of

The non-availability of the sophisticated anaesthetic
machine and the necessary equipment to administer inhalant
anaesthetic in the field hospitals make their use practically
unfeasible for the field veterinarians. Infield conditions,
intramuscular or intravenous anaesthesia are usually the
method of choice, as it can be performed with limited facilities
at hand in the animal hospitals. Total intravenous
anaesthesia (TIVA) is a method of general anaesthesia that
uses agents given solely by the intravenous route and in
the absence of all inhalation agents (Campbell et al., 2001).
The concept of total intravenous anaesthesia (TIVA) is
simple. An I/V line is the only prerequisite and everything
needed for general anaesthesia is supplied through this line.
The TIVA provides a reliable, rapid, inexpensive and smooth
induction of anaesthesia, adequate hypnosis and analgesia
as well as rapid, uncomplicated and complete recovery for
discharge in “home-fit” condition to the owner within minutes
Veterinary Sciences and Animal Husbandry, Central Agricultural
University, Selesih, Aizawl-796 014, Mizoram, India.
1
Department of Veterinary Medicine, College of Veterinary Sciences
and Animal Husbandry, Central Agricultural University, Selesih,
Aizawl-796 014, Mizoram, India.
Corresponding Author: Kalyan Sarma, Department of Veterinary
Medicine, College of Veterinary Sciences and Animal Husbandry,
Central Agricultural University, Selesih, Aizawl-796 014, Mizoram,
India. Email: kalyan_srm@rediffmail.com
How to cite this article: Saikia, B., Sarma, K.K. and Sarma, K.,
Effects of Propofol, Ketamine and their Combination (ketofol) as
Total Intravenous Anesthesia (TIVA) on Haematological, Serum
Biochemical and Hormonal Profile in the Surgical Management of
Canine Patients. Indian Journal of Animal Research. ():
Submitted: 01-08-2020 Accepted: 16-12-2020 Online:
 Effects of Propofol, Ketamine and their Combination (ketofol) as Total Intravenous Anesthesia (TIVA) on Haematological...
of completion of the procedure. The TIVA always involves
the delivery of a bolus dose or a fast loading infusion to
achieve an adequate blood concentration of the anaesthetic
drug. Maintenance of anaesthesia can be obtained by
administering intermittent boluses, continuous rate of infusion
or by target-controlled infusion. Therefore, the present study
was undertaken with the objectives to evaluate the certain
haematological, serum biochemical and hormonal profile of
propofol, ketamine and their combination ‘Ketofol’ as a TIVA
in atropine and xylazine premedicated dogs.
MATERIALS AND METHODS
Ethical approval
Before the conduct of the experiment, Institutional Animal
Ethics Committee approval was obtained for this study (77/
ac/CPCSEA/FVSc/AAU/IAEC/15-16/358, dated 10/04/2015).
Selection of animals
The study was conducted in eighteen clinical cases of dogs
that were brought for elective ovariohysterectomy or
castration. The animals were divided into three groups as
shown in Table 1. Food and water were withheld from each
dog 12 hours before the surgery as a routine pre-anesthetic
preparation. Each dog was weighed before the experiment
using a digital weighing scale (CTG 200, Aczet Private
Limited, India).
Evaluation of haemato-biochemical, minerals and
hormonal parameters
An intravenous catheter was placed into the cephalic vein
of each dog and 5 ml (1ml for haematology and 4ml for
serum) of blood at each assessment period collected in
vacutainer tubes with and without ethylene diamine tetra
acetic acid (EDTA) for evaluation of haematological and
biochemical parameters. Blood samples were collected at
time zero before drug administration and at 15, 30, 60 and
90 minutes after induction of anesthesia for the estimation
of total erythrocyte count (TEC) in millions/ mm 3, total
leucocyte count (TLC) in millions/ mm3, packed cell volume
(PCV) in %, haemoglobin concentration (HB) in g/dl.
Table 1: Total intravenous anesthesia (TIVA) protocols in dogs.
No. of Pre anaesthetic
Group
animals Dose and route
I 6 Atropine@0.04mg/kg I/M,
Xylazine @ 0.5 mg/kg,I/M
II 6 Atropine@0.04mg/kgI/M,
Xylazine @0.5 mg/kg,I/M
III 6 Atropine@0.04mg/kg I/M,
Xylazine @ 0.5 mg/kg,I/M
2 Indian Journal of Animal Research
Haematological parameters were analyzed with the help of
automated blood cell counter (MS4e, France) and
biochemical parameters viz. glucose, protein, alanine
aminotransferase (ALT), aspartate aminotransferase (AST),
Gamma-glutamyl transferase (GGT), lactate dehydrogenase
(LDH), blood urea nitrogen (BUN) and creatinine were
estimated using standard diagnostic kits manufactured by
Span Diagnostics, Surat, Gujarat on the semi-automated
biochemical analyzer (Chemistry Analyzer-CA 2005 B4B
Diagnostic division, China, Model no. CA 2005). Sodium
and potassium were analyzed by flame photometry (Corning
410 C®, Medical Corning Medfield, USA) method at 589
nm for sodium and 768 nm for potassium. Chloride was
measured by the colorimetric method by using a kit by Bayer
Diagnostic India Limited. Serum cortisol was measured with
an electrochemiluminescence immunoassay on a cobas
analyser (Roche diagnostics, Mannheim, Germany). The
triiodothyronine (T3) and thyroxine (T4) levels were measured
by performing radioimmunoassay (RIA) as previously
described (Paradis et al., 2003).
Statistical analysis
The data were structured in the Microsoft Excel spreadsheet.
Statistical analysis was performed using windows based
statistical package viz Microsoft Excel and SPSS.
RESULTS AND DISCUSSION
Haematological observations
The Effects of propofol, ketamine and their combination
(ketofol) as total intravenous anaesthesia (TIVA) on
haematological parameters are shown in Fig 1. In all the
three groups, haemoglobin, PCV and TEC level showed a
significant (P<0.05) decrease at 30 to 60 minutes.
Thereafter, it returned gradually to the pre-induction level.
The values of TLC did not register any significant change at
the different time intervals of TIVA in all three groups. But
there was an insignificant decrease up to 60th minute in all
the groups. In the case of neutrophil, there was insignificant
neutrophilia of up to 60th minute in all the groups whereas
Anesthetic dose and Anaesthetic dose and route for
route for Induction Maintenance up to 90 minutes
Propofol @ 5mg/kg,I/V Propofol @ 2.5mg /kg, I/V (as Intermittent
Bolus Injection) each time as required when
the movement was detected on the application
of noxious stimuli for 90 minutes.
Ketamine @ 5mg/kg, I/V Ketamine @ 2.5 mg /kg I/V (as Intermittent
Bolus Injection) each time as required when
movement was detected on application of
noxious stimuli for 90 minutes.
Ketofol @ 2 mg of each Ketofol@ 1mg of each drug /kg, I/V (as
drug /kg, I/V Intermittent Bolus Injection) each time as
required when the movement was detected
on the application of noxious stimuli for 90 minutes.
 Effects of Propofol, Ketamine and their Combination (ketofol) as Total Intravenous Anesthesia (TIVA) on Haematological...

Fig 1: Effect of anaesthetic treatment on Hb, PCV, TEC and TLC at different time interval in dogs.

Fig 2: Effect of anaesthetic treatment on the Differential leukocytic count at different time interval in dogs.

monocytes and eosinophil levels were insignificantly
decreasing at 15minutes and 30minutes respectively in all
three groups (Fig 2). Thereafter, it returned gradually to the
pre-induction level. The findings of the present study
concurred with Sankar et al. (2011) who had also observed
a decrease in Hb, PCV, TEC, monocytes, eosinophil and
neutrophilia during ketamine or propofol anaesthesia in
acepromazine-xylazine premedicated dogs. Other workers
are also reported similar results during the continuous
infusion of propofol (Jena et al. 2014, Ratnesh et al. 2014),
ketofol (Kumar et al. 2014) and ketamine anaesthesia
(Venugopal et al. 2002) in dogs. The decreasing trend of
haematological parameters in the present experiment might
be due to the splenic pooling of erythrocytes that occur with
most of the other anaesthetics. The Insignificant neutrophilia
might be due to the anaesthetic stress. The painful surgeries
along with the anaesthetic stress lead to severe stress to
the animal (Sankar et al., 2011). The stress leads to
stimulation of the adrenal cortex leading to glucocorticoid
production which acts on the circulating neutrophils. An
increase in neutrophilic count also observed by Mukati et al.
(2006), Butola and Singh (2003) and Carroll et al. (1998)
during the induction of different anaesthetic protocols in
dogs.
Biochemical observation
Effect of anaesthetic treatment on Glucose, protein, BUN
and creatinine
The Effects of propofol, ketamine and their combination
(ketofol) as total intravenous anaesthesia (TIVA) on glucose,
protein, BUN and creatinine parameters are shown in Fig 3.
The blood glucose level was significantly (p<0.05) increased
in all the groups until the end of the experiment after the
administration of anaesthetic drugs. A similar observation
was also reported by Costa et al. (2013) and Ratnesh et al.
(2014) during propofol anaesthesia and Ajadi et al. (2008)
and Malik et al. (2011) during propofol or ketamine
anaesthesia in xylazine premedicated dogs. An increase in
serum glucose level might be due to decreased membrane
transport of glucose, decreased glucose utilization; inhibition
of insulin release mediated by alpha-2 receptors in
pancreatic beta cells and increased blood concentration of
the adrenocortical hormone. On the other hand, the total
protein level was insignificantly decreasing up to the 30 th

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 Effects of Propofol, Ketamine and their Combination (ketofol) as Total Intravenous Anesthesia (TIVA) on Haematological...

minute of TIVA in all the groups. Similar findings were also
reported by Bayan et al. (2002), Camkerten et al. (2013)
and Jena at.al (2014) during the uses of different anaesthetic
protocols in dogs. The initial reduction of total protein during
TIVA in all three groups might be attributed to the expanded
intravascular volume arising from the extravascular
compartment reported by Sankar et al. (2011). A significant
increase in BUN and creatine value was recorded in group-
I and group-II than group-III at different time intervals up
to the end of the experiment. It might be due to the
temporary inhibitory effects of individual anaesthetics drugs
on the renal blood flow leading to a decrease in glomerular
filtration rate.
Effect of anaesthetic treatment on different enzymes
The Effects of propofol, ketamine and their combination
(ketofol) as total intravenous anaesthesia (TIVA) on ALT,
AST, GGT and LDH are shown in Fig 4. The ALT values
were significantly (p<0.05) increased up to 60 th minutes
during TIVA and thereafter gradually decreased towards the
pre-anaesthetic level at the end of the observation. An
increase in serum ALT was also observed in xylazine,
propofol and ketamine anaesthesia in West African dwarf
goats by Okwudili et al. (2014). The increase ALT during
TIVA might be due to hypotension in combination with
hypoxemia might have caused the release of these enzymes
from the heart muscles or liver (Okwudili et al., 2014).

Fig 3: Effect of anaesthetic treatment on biochemical parameters at different time interval in dogs.

Fig 4: Effect of anaesthetic treatment on ALT, AST, GGT and LDH at different time interval in dogs.

4 Indian Journal of Animal Research

 Effects of Propofol, Ketamine and their Combination (ketofol) as Total Intravenous Anesthesia (TIVA) on Haematological...

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Fig 5: Effect of anaesthetic treatment on Ca, Na, K and Cl at different time interval in dogs.

Similarly, a significant increase AST value was recorded in

group-II at 30 th and 60 th minute of the experiment in
comparison to group-I and group-III which might be indicative
of propofol and ketofol had a less adverse effect on different
body tissues than ketamine. The transient variation in GGT
values in the present experiment were within physiological
limits might be indicative of nontoxic/less harmful effect of
all the anaesthetic drugs on the hepatobiliary system.
Insignificant increased LDH value during TIVA in all the
groups and remained within the physiological limit might
be concluded that all three anaesthetics might safely be
used.
Effect of anaesthetic treatment on minerals
The effects of propofol, ketamine and their combination
(ketofol) as total intravenous anaesthesia (TIVA) on Ca, Na,
K and Cl are shown in Fig 5. There were no significant
differences in calcium values within the groups that were
recorded up to the end of the experiment. It could be
concluded that all three anaesthetic agents do not affect
serum calcium in dogs. The sodium (Na) and chloride (Cl)
values insignificantly increased up to 60 minutes and
thereafter decreased in all the groups. Similar findings were
also observed by Camkerten et al. (2013) during xylazine-
ketamine anaesthesia in dog and Ratnesh et al. (2014)
during propofol anaesthesia in buffalo calves. An increase
in plasma sodium and chloride (Cl) level in the present study
might be due administration of NSS during general
anaesthesia which has also been reported by Khanna et al.
(1997). A decrease in serum potassium level was observed
in all the groups but these values were within physiological
limit. However, the decreased level of potassium might be
associated with the migration of potassium from extracellular
to intracellular space or might be related to administration Fig 6: Effect of anaesthetic treatment on cortisol, T3 and T4 at
of potassium free parental fluid (Mathews, 2007) and these different time interval in dogs.

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 Effects of Propofol, Ketamine and their Combination (ketofol) as Total Intravenous Anesthesia (TIVA) on Haematological...
change might also be due to haemodilution in response to
vasodilatation, that conformed with the findings of Butola
and Singh (2003) after ketamine-midazoalm administration
in dogs and Ratnesh et al. (2014) during propofol
anaesthesia in buffalo calves.
Effect of anaesthetic treatment on the hormonal level
The effects of propofol, ketamine and their combination
(ketofol) as total intravenous anaesthesia (TIVA) on cortisol,
T3 and T4 are shown in Fig 6. A higher level of cortisol values
were recorded in group-I animals for the entire period of
observation followed by group-II animals and the least
cortisol values were recorded in group-III animals as
compared to group-I and group-II animals. The high cortisol
value in group-I animals for the entire observation period
might be due to more stress produced by pain during/after
surgery as propofol have no or little analgesic property
(Robertson et al., 1990). The serum triiodothyronine (T3)
and thyroxine (T4) values showed a non-significant
fluctuation within their physiological limits at different time
intervals of TIVA in all three groups. There was no significant
difference among the three groups at different time intervals
during TIVA. Similar findings were also reported by Baishya
(2011) in yak anaesthetised with medetomidine-ketamine
and xylazine-ketamine.
CONCLUSION
In all the three experimental groups, an initial significant
decline was observed in Hb, PCV and TEC which steadily
returned to the pre-anaesthetic level at the end of the
observation. Significant increase in glucose, BUN, creatinine
ALT, AST and GGT values were recorded in all the groups
in the early phase of the experiment then showed a declining
trend towards the pre- anaesthetic level at the end of the
experiment. The magnitude of the increasing trend of
glucose was higher whereas the increasing trend of
creatinine, BUN, ALT, AST GGT was lesser in group-III than
group-I and group-II animals. The cortisol values in group-
III animals also increased with time but the magnitude of
these changes was least compared to group-I and group-II
animals. From this study, it can be concluded that propofol
- ketamine combination (ketofol) can be considered as total
intravenous anaesthesia (TIVA) to surgical management of
canine patients in comparison with propofol and ketamine
alone as it has the least effect on the haemato-biochemical
and hormonal level during the induction period.
ACKNOWLEDGEMENT
The authors are highly thankful to the Vice Chancellor,
Assam Agricultural University and Dean College of
Veterinary Science, Khanapara for providing necessary
facilities to carry out this study.
Conflict of interest
The authors declare that they have no conflict of interest.
6 Indian Journal of Animal Research
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