Indian Journal of Animal Research

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Research Article

Indian Journal of Animal Research, volume 56 issue 7 (july 2022) : 866-872

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 Saikia1, Kushal Konwar Sarma1, Kalyan Sarma2,*
1Department of Veterinary Surgery and Radiology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University, Selesih, Aizawl-796 014, Mizoram, India.
2Department of Veterinary Medicine, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University, Selesih, Aizawl-796 014, Mizoram, India.
Cite article:- Saikia Basanta, Sarma Konwar Kushal, Sarma Kalyan (2022). 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. 56(7): 866-872. doi: 10.18805/IJAR.B-4268.

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 30 mints 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 T3. 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. 

INTRODUCTION

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 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).
 

Table 1: Total intravenous anesthesia (TIVA) protocols in dogs.


 
Evaluation of haemato-biochemical, minerals and hormonal parameters
 
An intravenous catheter was placed into the cephalic vein of each dog and 5 ml (1 ml for haematology and 4 ml 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/mm3, total leucocyte count (TLC) in millions/mm3, packed cell volume (PCV) in %, haemoglobin concentration (HB) in g/dl. 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 monocytes and eosinophil levels were insignificantly decreasing at 15 minutes and 30 minutes 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.
 

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.


 
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 30th minute of TIVA in all the groups. Similar findings were also reported by Bayan et al., (2002), Camkerten et al., (2013) and Jena et 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.
 

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


 
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 60th 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). Similarly, a significant increase AST value was recorded in group-II at 30th and 60th 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.
 

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


 
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 of potassium free parental fluid (Mathews, 2007) and these 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.
 

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


 
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.
 

Fig 6: Effect of anaesthetic treatment on cortisol, T3 and T4 at different time interval in dogs.

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.

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