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Haemato-Biochemical Evaluation of Ketamine or Butorphanol as Analgesic in Xylazine and Propofol Anaesthesia in Canine Ovariohysterectomy

Kumari Chandrakala Arvind Kumar Sharma Laxmi Kumari Raju Prasad Kaushal Kumar Singh Praveen Kumar
Vol 7(7), 146-152
DOI- http://dx.doi.org/10.5455/ijlr.20170521042951

The objective of present study was to evaluate the haematobiochemical profiles following administration of ketamine or butorphanol as preanaesthetic analgesic in xylazine -propofol anaesthesia in elective ovariohysterectomy procedure. All dogs were divided randomly in to two groups of five animals in each and designed as Group I and Group II. Atropine sulphate was injected s/c @ 0.04 mg/kg b.wt. 5 min. prior to each treatment in the animals of both the groups. Group I, received xylazine @ 1 mg/kg bwt IM and Ketamine @ 3 mg/kg b.wt, IM whereas, animals of group II were administered with xylazine @ 1 mg/kg b.wt. IM and Butorphanol @ 0.2 mg/kg b.wt, IM. Surgical anaesthesia was induced by administration of propofol “to effect” 15 min after preanaesthetics and maintenance of anaesthesia was carried out for 30 min (Maximum operative time to complete ovariohysterectomy procedure) with continuous rate infusion technique of propofol @ 0.3 mg/kg/min. Lymphocytopenia and relative neutrophilia was the consistent findings; where as other haematological parameters did not revealed any significant changes. The biochemical parameters (BUN, creatinine, ALT and AST) were non-significantly variables, whereas, hyperglycemia was the noticed at 1 hr interval in both the groups. Changes in total protein were transiently variable. In conclusion, transient variables were within the physiological limits have been reported following ketamine or butorphanol as preanaesthetic analgesic in xylazine and propofol induced anaesthesia which further maintained with continuous rate infusion of propofol @0.3 mg/kg/min. Hence, these combinations of anaesthesia can be used safely in compromised animal and clinically healthy animals.


Keywords : Bitch Butorphanol Haemato-Biochemical Changes Ketamine Propofol Ovariohysterectomy

Introduction

Propofol, a relatively a new intravenous anaesthetic agents found to be suitable for anaesthesia by a number of clinical trial (Briggs et al., 1983). Its duration of action is shorter, owing to its rapid metabolism through liver by glucuronide conjugation (Simon et al., 1988). Mani and Morton (2010) reported the rapid onset of action, independent of ventilation status, reduction of adverse effects of other anaesthetic drugs for balanced anaesthesia protocols, provision of continuous analgesia if needed, smoother recovery, low costs and reduction of the hazards of occupational health and atmospheric pollution on administration of propofol. Propofol combined with ketamine (ketofol) results in higher pulse rate and mean arterial pressure with lower respiration rate (Martinez-Taboada and Leece 2014). Anaesthetics with variable combination produced no- significant effect with use of nalbuphine (Harish et al., 2015) and significant effect with xylazine and propofol (Dewangan et al., 2016) on its haemato – biochemical profiles. The present paper deals the haemato- biochemical changes following administration of ketamine or butorphanol as analgesia in xylazine and propofol induced anaesthesia which further maintained by continuous rate infusion techniques of propofol in canine ovariohysterectomy.

Materials and Methods

The present study was conducted in 10 dogs of varying age group presented to the department for elective ovariohysterectomy. Normal healthy dogs based on history, complete physical examination, CBC and serum chemistry analysis were included. Owner consent for the use of the dogs and institutional ethical approval was obtained prior to inclusion of dogs in the study. Animals were admitted to the R.V.C Clinical complex in the morning of the surgery with overnight fasting and 6hrs withheld of water. All dogs were divided randomly into two groups of five animals in each and designed as Group I and Group II. Atropine sulphate was injected s/c @ 0.04 mg/kg b.wt., 5 min., prior to each treatment both the groups. Group I, received xylazine @ 1 mg/kg b.w.t IM –Ketamine @ 3 mg/kg b.wt, IM whereas, animals of group II were administered with xylazine @ 1 mg/kg b.wt. IM –Butorphanol @ 0.2 mg/kg b.wt, IM. Surgical anaesthesia was induced by IV administration of propofol “to effect” 15 min after preanaesthetics and maintenance of anaesthesia was carried out for 30 min (Maximum operative time to complete ovariohysterectomy procedure) with continuous rate infusion of propofol @ 0.3mg/kg/min. The evaluation and comparison was done on the basis of haematological and biochemical parameters. Haemato-biochemical parameters namely Hb, PCV, TLC, DLC, blood urea nitrogen, creatinine, and blood glucose, total protein ALT and AST recorded at 0 min (base line) and at 30, 60 and 120 min, 4 hrs and 24 hrs of drugs administration.

Statistical Analysis

ANOVA (Analysis of variance) and DMRT (Duncan Multiple Range Test) were used to compare the means at different intervals with base values as per the method suggested by Snedecor and Cochran (2004).The level of significance was set to be 0.05.

Results and Discussion

The values of haemoglobin and packed cell volume recorded at different intervals did not reveal any significant variation within and among the groups. However, the values recorded at 1, 2 and 4 hrs in group I and II showed a non-significant fall (P>0.05) as compared to the baseline. The values in group II (butorphanol) remained stable throughout the observation period (Table 1).

Table 1: Mean ±S.E. value of haemoglobin (gm/dl), PCV (%), TLC (x103/µl) and DLC (%) before and after administration of drugs in the animals of groups I, and II

Groups Groups Period of Observation (in Hours)
0 0.5 1 2 4 24
Hb I 14.64±0.60 14.48±0.68 13.92±0.57 14.2±0.60 14.48±0.63 14.52±0.65
II 15.12±0.65 15.32±0.65 14.76±0.61 14.76±0.58 14.84±0.65 14.96±0.62
PCV (%) I 43.44±02.02 42.84±1.83 42.64±1.82 42.6±1.81 42.96±2.07 43.08±2.14
II 45.36±1.95 45.96±1.95 44.26±1.86 44.4±1.83 44.4±1.98 44.88±1.87
TLC I 9.89±1.18 9.79±1.16 9.41±1.16A 9.62±1.16 9.69±1.13 9.90 ±1.13
II 11±1.51 10.78±1.42 10.75±1.42B 10.72±1.46 10.79±1.50 11.01±1.47
Neutrophils I 65.15±2.10 65.54±1.99 66.08±2.13 66.22±2.16 66.31±2.04 66.3±2.03
II 63.97±1.08 63.92±1.10 63.99±1.11 64.29±1.17 64.38±1.19 64.45±1.20
Lymphocytes I 24.81±0.30c 23.45±0.20ab 23.08±0.26a 23.83±0.32b 24.6±0.12bC 24.82±0.13c
II 23.6±0.30b 23.72±0.28b 23.68±0.30b 23.75±0.37a 24±0.30abAB 23.59±0.34ab
Eosinophils I 7±0.06b 6.64±0.28ab 6.32±0.21a 6.48±0.15a 6.56±0.10ab 6.68±0.05ab
II 6.96±0.10b 6.58±0.13a 6.52±0.14a 6.57±0.13a 6.57±0.12a 6.73±0.13ab
Monocytes I 5.91±0.14aA 6.08±0.14ab 6.32±0.15b 6.06±0.04ab 5.98±0.07a 6.05±0.04ab
II 6.45±0.21B 6.59±0.28 6.36±0.24 6.2±0.21 6.3±0.23 6.35±0.22

Group I: Xylazine + Ketamine + Propofol, Group II: Xylazine + Butorphanol + Propofol. Value marked with different superscript with small letter (a, b…) in a row and capital letter (A, B…) in column differ significantly (P<0.05).

The decrease in haemoglobin and packed cell volume might be due to shifting of fluids from the extravascular compartment to the intravascular compartment in order to maintain the cardiac output in the animals (Wagner et al., 1991) or due to splenic pooling of RBC.

Combination of ketamine-midazolam has been reported to cause a decrease in haemoglobin values in dogs (Butola and Singh, 2007). Kappa mediated diuretic effect of butorphanol also causes decrease in packed cell volume (Turi and Sharma 2015). PCV values appear unaltered when xylazine is used in combination with low and high doses of propofol in horses (Mama et al.,1998). Ketamine, propofol and acepromazine also cause vasodilation, altering the vascular wall tone (Wilson et al., 2004). These effects of anaesthetics explained the vasodilation of splenic blood vessels, respectively the changes in CBC parameters during anaesthesia. A non significant decrease in mean TLC value had been observed during the peak of anaesthesia in both the groups (Table 1). The administration of α2-agonists suppresses the circulating catecholamines by exerting a modulating effect on leukocyte subpopulations (Kaname et al., 2002). Dissociation agents also reduce leukocyte counts (Umar and Adam, 2013). Fall in TLC was also explained with fact that ketamine in group I and butorphanol in group II produced analgesic effect which reduced the stress response by decreasing the plasma cortisol and adrenaline, and was responsible for transient fall in TLC.

A transient increase in neutrophil and relative decrease in lymphocyte was observed in both the groups post injection. The increase in neutrophils and relative decrease in lymphocytes might be due to stimulation of lymph nodes caused by stress. In contrast to present study, Amarpal et al. (1998) had reported a decreased neutrophil count after administration of alpha-2 agonists in dogs. The values of lymphocytes exhibited a significant fall up to 2 hrs of observation as compared to base line value. Whereas, the values recorded at 4 and 24 hrs was non-significant and as compared to baseline value. Zlateva and Marinov (2015) also reported the lymphopenia and corresponding neutrophilia with use of different anaesthetic combination in ovariohysterectomy. A decreasing trend in the eosinophils post anaesthesia could be observed in both the groups. The transient increase in monocyte at initial intervals might be attributed to steroid release provoked by stress due to anaesthesia. A gradual and non significant increase in BUN and creatinine level was observed followed by a gradual decrease to reach near the base value at 24 hr of observation in both the groups. Maximum increase in value of BUN and creatinine was observed at 1hr post injection in both the groups (Table 2). Transient but non-significant increase at 1 hr of observation in both groups might be attributed to increased level of anti diuretic hormone (ADH) and decreased glomerular filtration as emphasized by Anandmay (2009) in dogs after propofol with or without opioids. The maximum increase in blood glucose level was noticed at 1 hr which tended to reach near the base value at 24 hr post injection in both the groups (Table 2). Hyperglycemia was also recorded after administration of propofol-midazolam (Bayan et al., 2002) and propofol-buprenorphine, propofol-meperidine and propofol-pentazocine (Anandmay, 2009) in canine. Rise in glucose level was attributable due to activation of the sympathoadrenal system releasing adrenaline which in turn mobilized glycogen from liver during anaesthesia. Xylazine used as preanaesthetic in both the groups might be induced hyperglycemia by suppressing insulin release, stimulating glucagon release, or both, in α and β cells of the pancreas, respectively (Angel and Langer, 1988).

Table 2: Mean ±S.E. value of BUN (mg/dl), creatinine (mg/dl), glucose (mg/dl), AST(IU/L), ALT (IU/L) and total protein (gm/dl) before and after administration of drugs in the animals of groups I and II

Groups Groups Period of Observation (in Hours)
0 0.5 1 2 4 24
BUN I 11.74±2.24 11.74±2.24 12.75±1.79 12.5±1.58 12.34±1.76 12.1±1.99
II 9.84±0.50 9.95±0.49 10.29±0.43 10.6±0.43 10.28±0.43 9.52±0.46
Creatinine I 1.07±0.06 1.08±0.06 1.21±0.09 1.18±0.09 1.1±0.04 1.08±0.04
II 1.08±0.07 1.1±0.05 1.19±0.08 1.25±0.11 1.1±0.07 1.07±0.04
Glucose I 67.29±2.22a 69.86±2.56ab 81±2.92c 75.2±2.24bc 67.9±2.04a 65.6±2.79a
II 71.84±4.61a 73.7±4.21a 87.4±3.37b 80.8±2.96ab 74.2±4.33a 70.52±4.92a
AST I 34.26±0.13 34.5±0.33 35.93±0.79 34.78±0.36 34.4±0.19 34.03±0.68
II 33.68±2.57 35.4±2.51 37.18±2.53 32.82±1.30 33.35±1.77 33.3±2.53
ALT I 36.7±3.38 37.75±3.43 38.61±3.23A 39.44±2.81 36.99±2.86 35.78±3.34
II 43.82±6.26 46.05±5.31 53.69±6.46B 46.85±5.99 45.55±5.29 42.68±4.85
Total protein I 6.43±0.17c 6.48±0.37c 5.45±0.44abA 5.35±0.11aA 5.86±0.14abc 6.14±0.13bc
II 6.26±0.25 6.83±0.41 6.86±0.27B 6.67±0.34B 6.65±0.41 6.88±0.31

Group I: Xylazine + Ketamine + Propofol, Group II: Xylazine + Butorphanol + Propofol. Value marked with different superscript with small letter (a, b…) in a row and capital letter (A, B…) in column differ significantly (P<0.05).

ALT and AST activity was found to be non-significantly elevated up to 2 hrs of administration, thereafter, the values returned near to the base line by end of observation in both the groups (Table 2). Marked elevation after drug administration was noticed in group II (butorphanol) at 1 hrs as compared to group I. Non significant increase in ALT and AST level might be associated with increased cell membrane permeability in response to haemodynamic changes induced by anaesthetic agents. Most ALT activity in the opioid group might be attributed to the fact that the opioids are exclusively metabolized in liver hence causes no more changes at cellular level (Scott and Perry, 2000). Propofol was rapidly cleared by hepatic and perhaps, extrahepatic metabolism and was mainly metabolized by glucuronide conjugation in liver (Kanto and Gepts, 1989). Metabolism of ketamine occurred in the liver in most of the species including humans, horses and dogs (Kaka et al., 1979). Butorphanol was cleared in hepatic by hydroxylation and dealkylation and conjugation. Propofol along with ketamine or butorphanol were mainly metabolized in liver. So the transient increase in ALT and AST level might be due to hepatic metabolism of these drugs which returned back to the normal physiological level indicating no undesirable effect on liver.

Total serum protein showed a significant variation in group I and non-significant variation in group II at respective intervals within groups. Group-wise analysis of data revealed a significant increase in the value recorded at 1 and 2 hours of observation in both the groups (Table 2). More significant change was observed in group I as compared to group II. Similar finding was recorded by Bayan et al., 2002, and Chandrashekharappa and Ananda (2009) by using different combinations of anaesthetic with propofol in canine. The measurement of total serum protein was of limited value. It might be altered by change in plasma volume; an increase was caused by dehydration and a decrease from overload with water. The non- significant increase in group II at 1 hrs might be due to increase globulin levels after start of inflammation process in the operated animals. Kim and Jang, (1999) reported that significant increase in total protein and albumin values was noticed after propofol anaesthesia in dogs premedicated with xylazine.

Conclusion

In conclusion, transient variables were within normal physiological limits have been reported following ketamine or butorphanol as preanaesthetic analgesic in xylazine and propofol induced anaesthesia which further maintained with continuous rate infusion of propofol @0.3 mg/kg/min. Hence, these combinations of anaesthesia can be used safely in compromised animal and clinically healthy animals.

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