STRESS RESPONSE AND HAEMATOLOGICAL CHANGES DURING OVARIOHYSTERECTOMY AFTER DEXMEDETOMIDINE, BUTORPHANOL/ PENTAZOCINE, MIDAZOLAM AND KETAMINE ANAESTHESIA IN DOGS

Malik Abu Rafee1, Prakash Kinjavdekar2, Amarpal3and Hari Prasad Aithal2
1Ph.D. Scholar, 2Principal Scientist, 3Head of Division, Division of Surgery, ICAR-Indian Veterinary Research
Institute, Izatnagar-243122, Bareilly (Uttar Pradesh) India.
[Received: 24.4.2017; Accepted: 30.10.2017]
{DOI 10.29005/IJCP.2017.9.2.151-154}

The study was conducted on 24 atropinized healthy female dogs undergoing ovariohysterectomy, to evauate
stress response and haematological changes. Atropine (0.04 mg kg-1) followed by dexmedetomidine (20μg kg-1) after 5 min IM were administered to each animal. Animals were randomised into groups D, DB and DP of eight animals each. Group D animals did not receive any opoids whereas, groups DB and DP received butorphanol (0.1mg kg -1) and pentazocine (3mg kg -1) IM, respectively. After 10 min of premedication, anaesthesia was induced with midazolam (0.8 mg kg-1) IV, in all the groups and maintained with 1% ketamine as and when required. Cortisol has not changed significantly as compared to the baseline. Plasma insulin decreased marginally in all groups; however, plasma glucose remained significantly higher than the baseline value in all groups. It was concluded that basal anaesthesia with Dexmedetomidine prevented the development of stress response to surgery.
Key words: Anaesthesia, Dogs, Haematological, Ovariohysterectomy, Stress

The stress response is the name given to the hormonal and metabolic changes which follow injury or trauma (even surgical trauma). There has been a great deal of interest in the modification of the stress response with respect to the potential beneficial effects on surgical outcome. The extent to which the responses are modified
depends on the different anaesthetic drugs used. The opioids suppress hypothalamic and pituitary hormone secretion (Desborough and Hall, 1989). The benzodiazepine, like midazolam, attenuates the cortisol responses
to both peripheral and upper abdominal surgery (Crozier et al., 1987; Desborough et al., 1991). Alpha-2 agonists directly or indirectly obtund the stress response when administered systemically. Reduction in the perception of stressors is achieved indirectly through sedation and analgesia while directly by inhibiting neuroendocrine response.
The purpose of this study was to evaluate the efficacy of preanaesthesia with dexmedetomidine and its combinations with butorphanol or pentazocine with midazolam and ketamine for induction and maintainence
of anaesthesia, respectively, to obtund stress response observing changes in neutrophil count, cortisol, glucose and insulin brought about by ovariohysterectomy in dogs.

Material and Methods
The study was designed as randomized, blinded, prospective clinical study, with written and informed owner
consent. 24 Client owned, apparently healthy mixed breed female dogs weighing 12.29±3.44 kg (mean± SD), undergoing elective ovariohysterectomy were administered atropine (0.04 mg kg-1) followed by dexmedetomidine I/M (20μg kg-1) after 5 min and randomly divided into group D, group DB and group DP, each consisting of
eight animals. Group D animals did not receive any opoids whereas, groups DB and DP received butorphanol (0.1mg kg -1) and pentazocine (3mg kg -1) I/M, respectively. After 10 min of premedication, midazolam
(0.8mg kg -1) was administered I/V for induction of anaesthesia in all the animals. The anaesthesia was maintained with 1% ketamine as and when needed, I/V.
One ml venous blood was collected in heparinized (1:1000) disposable syringes, at 0 min (base line), 30, 60 and 120 minutes after administration of the drugs and subjected for the estimation of following parameters: 1. Haemoglobin (Hb) was estimated using Sahli’s haemoglobinometer and values were expressed in g/L. 2. Packed cell volume
(PCV) was estimated by microhaematocrit method and values were expressed in L/L. 3. Total leukocyte count (TLC) was estimated by using Neubauer counting chamber and values were expressed in X109/L. 4. Differential
leukocyte count (DLC) a thin blood smear was prepared, stained and cells were counted by the method described by standard method and values were expressed in percent.

Biochemical observations
Four ml venous blood was collected in heparinized (1:1000) disposable syringes (sodium fluoride for glucose) at 0 min (base line) and at 30, 60 and 120 min after injection of drug(s). The blood samples were centrifuged at 3000 rpm for 5 min and plasma was separated and stored at -20 0C until assayed. The plasma samples were subjected
for the estimation of following parameters: 1. Plasma urea nitrogen was estimated by diacetyl monoxide (DAM) method and values were expressed in mmol/L. 2. Plasma glucose was estimated by GOD/POD method and
values were expressed in mmol/L. 3. Plasma creatinine was estimated by alkaline picrate method and values were expressed in μmol/L.

Statistical analysis
The data was analyzed using repeated measures analysis with Proc GLM of SAS 9.2.

Results and Discussion Haematological Observations
In group D and DB Hb decreased significantly (P<0.05) at 60 and 120 min, in group DB, Hb decreased significantly
(P<0.05) and at all intervals as compared the baseline, respectively; while in group DP, Hb decreased significantly (P<0.05) only at 60 min as compared to baseline. At 30 min interval a significant (P<0.05) difference was recorded in group D as compared to groups DB and DP. There was no significant change in PCV in any group. The decrease in haemoglobin and PCV levels might be due to haemodilution in response to fluid therapy and/or shifting of fluids from the extravascular compartment to the intravascular compartment in order to maintain the cardiac output in the animals as also recorded by Wagner and Hitchcliff (1991) and Skarda and Muir (1994) or due to dexmedetomidine which has been shown to preserve blood flow to the most vital organs (brain, heart, liver and kidney) at the expense of organs like skin and pancreas as also mentioned by Lawrence et al. (1996). Combination of ketamine-midazolam has been reported to cause a decrease in Hb values in dogs. One or a combination of these
mechanisms might be responsible for the decrease in haemoglobin and PCV, in this study.

TLC decreased in general, but it was significant (P<0.05) at 120 min in group DB. No significant change was observed in neutrophil count in any group at any time interval with respect to baseline, however, significantly (P<0.05) difference was observed between group DB with respect to groups D and DP at baseline, 60 and 120 min
intervals. The TLC remained within the normal physiological range throughout the course of study. The marginal decrease in TLC in the present study can be attributable mainly to the administration of α2-agonists and decreased sympathetic activity. In earlier studies with alpha-2 agonists, a decrease in TLC has been noticed in dogs by Amarpal et al. (1998). However, in the present study, values of neutrophils fluctuated nonsignificantly around the baseline. Dexmedetomidine might have prevented the significant changes in neutrophil count by inhibiting neuroendocrine response (directly) or by producing better sedation and analgesia (indirectly) to obtund the stress response when administered systemically. The increase in neutrophil count after 30 min can be related to the anaesthetic and surgical stress and dexmedetomidine prevented severe changes resulting from stress. Significant

differences in the neutrophil count between group DB and groups D and DP at baseline and then at 60 and 120 min can be due to individual variation rather than effect of drugs.

Biochemical Observations
Cortisol is measured as an indicator of stress response. Under stressful conditions cortisol level has been reported to increase by Eberhard (1981). However in the present study remained marginally increased at most of the recording intervals in all the groups. In the present study the significant increase in cortisol was obtunded by exmedetomidine
due to inhibiting neuroendocrine response and proper level of sedation and analgesia. It has been reported that a delayed ACTH and cortisol response occurs in dogs undergoing ovariohysterectomy in which medetomidine
had been administered preoperatively by Benson et al., 2000) and the similar results were observed in the present study. The cortisol level dropped below the baseline initially and increased later (although insignificant).

There was significant increase (P<0.05) in plasma glucose from the baseline at all the intervals in all groups. Plasma insulin decreased initially and then increased marginally in all groups. Plasma urea nitrogen was also increased marginally in all the groups. In groups DB and DP plasma creatinine levels remained marginally below
the baseline and in group D, the levels remained marginally above the baseline values. There is a failure of the usual cellular response to insulin, the so‐called ‘insulin resistance’, which occurs in the perioperative period as also reported by Desborough (2000). Alpha-2 agonists have also been reported to induce an increase in serum
glucose by suppressing insulin release, stimulating glucagon release, or both, in α and β cells of the pancreas, respectively by Angel and Langer, 1988). Decreased in serum insulin and increase in blood glucose concentration has been reported hours following medetomidine administration in dogs and cats by Kanda and Hikasa (2008),
after medetomidine administration; in dogs, which received midazolam alone. Ketamine has been reported to cause sympathetic stimulation leading to release of catecholamines and increased glucose concentration in plasma as also reported by Ylitalo et al. (1976).

Plasma urea nitrogen and plasma creatinine remained within the normal physiological limits in all the groups. Gradual increase in plasma urea nitrogen was recorded up to 120 min but no significant difference was recorded at any time interval as compared to the baseline value. There were no significant differences in plasma creatinine
levels as well. Dexmedetomidine preserves blood supply to vital organs like brain, heart, liver and kidney at the expense of organs like skin and pancreas and this distribution is not affected by type of anaesthesia as also
recorded by Lawrence et al. (1996). This effect of dexmedetomidine and continuous intravenous fluid infusion might be responsible for adequate renal blood flow and enough glomerular filtration rates to maintain plasma urea nitrogen and creatinine values near the baseline.

From the study it was concluded that basal anaesthesia with Dexmedetomidine prevented the development of stress response to surgery as evidenced only marginal changes in neutrophil count, cortisol and insulin in this study.

References
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