Research article · 2018 · Full text
International Journal of Veterinary Sciences and Animal HusbandryComparative evaluation of haemato biochemical changes after intravenous administration of dexmedetomidine-butorphanol and dexmedetomidine-midazolam as preanaesthetic with propofol anaesthesia in dog
Volume 3(5) · Pages 71–78
Research areasVeterinary Pharmacology and AnesthesiaAnesthesia and Sedative AgentsAntibiotics Pharmacokinetics and Efficacy
Abstract
Author-writtenA combination of drugs may be preferred over the use of a single agent to induce deep sedation and the synergistic interaction between the drugs reduces the dose requirements of the drugs thereby minimising the unwanted side effects associated with each drug and improving recovery with this aim the present study was conducted to compare and evaluate the intravenous dexmedetomidine-butorphanol and dexmedetomidine-midazolam as preanaesthetic with propofol anaesthesia in dog. The study was conducted on 14 (fourteen) clinical cases of dogs of either sex, irrespective of age presented to the T.V.C.C., COVAS, Parbhani for various surgical interventions randomly divided into two groups each consisting of seven dogs. All the dogs in study were administered with inj. Atropine sulphate @ 0.04 mg/kg body weight subcutaneously. In group A, after administration of inj. Atropine sulphate, 10 min later combination of Inj. Dexmedetomidine HCL (10 µg/kg body weight) and Inj. But orphanol tartarate (0.2 mg/kg body weight) mixed in single syringe was administered intravenously whereas in group B, combination of Inj. Dexmedetomidine HCL (10 µg/kg body weight) and Inj. Midazolam maleate (0.2 mg/kg body weight) mixed in single syringe was administered intravenously. Quality of sedation was assessed followed by inj. Propofol was administered till the effect to get the surgical stage of anaesthesia and required amount was calculated as induction dose. Intermittent doses of propofol were given for maintenance of anaesthesia when required. Overall significant difference haemoglobin (P
Summary
Source-checkedPlain-language reading of the full paper, prepared with AI and checked against the text. Each point links to the authors' own words.
Why it matters
- Using drug combinations for sedation is often preferred over single agents because synergistic interactions can lower required doses, reducing side effects and improving recovery. View evidence ↗
- Alpha-2 adrenergic receptor agonists are valuable in anesthesia due to their ability to provide sedation, reduce anxiety, and provide analgesia while reducing the amount of other anesthetics needed. View evidence ↗
- Anticholinergic drugs are recommended when using alpha-2 agonists to prevent potential reductions in cardiac output and bradyarrhythmias. View evidence ↗
The question
- The study aimed to compare the hematological and biochemical changes in dogs receiving either a dexmedetomidine-butorphanol or a dexmedetomidine-midazolam preanesthetic combination followed by propofol anesthesia. View evidence ↗
What they did
- The study involved 14 dogs of any age or sex undergoing various surgical procedures at the Teaching Veterinary Clinical Complex in Parbhani. View evidence ↗
- Fourteen dogs were randomly split into two groups of seven, and all received a subcutaneous dose of Atropine sulphate at 0.04 mg/kg. View evidence ↗
- Group A received intravenous dexmedetomidine (10 µg/kg) and butorphanol (0.2 mg/kg), while Group B received intravenous dexmedetomidine (10 µg/kg) and midazolam (0.2 mg/kg). View evidence ↗
- Following sedation, propofol was administered to reach the surgical stage of anesthesia, with intermittent doses used for maintenance. View evidence ↗
- Blood samples were collected at four time points: before anesthesia, during sedation, during surgery, and 24 hours after recovery. View evidence ↗
What they found
- There was a statistically significant difference (P<0.01) in hemoglobin levels between the two groups across all measured time intervals. View evidence ↗
- Packed cell volume (PCV) showed no overall significant difference between groups, although a significant difference (P<0.05) occurred specifically during the sedation phase. View evidence ↗
- Total leucocyte count (TLC) exhibited no overall significant difference between the groups, except for a significant difference (P<0.05) during sedation. View evidence ↗
- Blood urea nitrogen (BUN) showed significant differences before preanesthesia (P<0.01) and during sedation (P<0.05), but no overall significant difference between the groups. View evidence ↗
- Blood creatinine levels showed significant differences during anesthesia (P<0.05) and recovery (P<0.01), but no overall significant difference between the groups. View evidence ↗
- There were no significant differences in blood glucose values between the two groups at any measured interval. View evidence ↗
- Alanine transaminase (ALT) showed significant differences at various intervals (P<0.05 to P<0.01), yet the overall difference between groups was non-significant. View evidence ↗
What it means
- The authors conclude that both dexmedetomidine-butorphanol and dexmedetomidine-midazolam are suitable preanesthetic combinations for propofol anesthesia in dogs, as they do not cause alarming or permanent changes to liver, kidney, or general physiological functions. View evidence ↗
Visual summary
1 visualsIllustrations explain the paper; they do not show study data.
Anesthesia Workflow
AI-generated conceptual illustration (domestic dogs). It explains the idea and does not show study data.
View source evidence ↗Figures & tables
From the original paper
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Figure 9Introduction
Anaesthesia is an indispensable pre-requisite for many surgical interventions with maximum technical efficiency and accuracy, so that surgeon can perform surgeries at ease. Propofol (2, 6-diisopropylphenol) is a newer generation injectable anaesthetic agent which was introduced in Veterinary medicine in the 1990's. The α2-adrenergic receptor agonists are useful adjuncts to anaesthesia because of their sedative, anxiolytic and analgesic effects and their anaestheticsparing properties. Anticholinergic premedication has been recommended with α2-agonists to prevent bradyarrhythmias and potential reduction in cardiac output produced by these agents. Dexmedetomidine was approved by the Food and Drug Administration at the end of 1999 for use in humans as a short-term medication (<24 hours) for analgesia and sedation in the intensive care unit (Gertler et al., 2001) [6] . Butorphanol is a centrally acting analgesic with both agonist and antagonist properties. Midazolam is a benzodiazepine with a fused imidazole ring that accounts for water solubility of the drug, exert their main sedative effect through Depression of limbic system and their muscle relaxing properties through inhibition of the internuncial neurons at spinal levels (Lumb and Jones, 2007) [13] . Keeping in view the above, the present study was planned with an objective of comparative evaluation of haemato biochemical changes after intravenous administration of dexmedetomidine-butorphanol and dexmedetomidine-midazolam as preanaesthetic with propofol anaesthesia in dog.
Materials and Methods
Materials and Methods
Selection of Animals
The present clinical study was conducted on 14 (fourteen) clinical cases of canine of either sex, irrespective of age presented to the Teaching Veterinary Clinical Complex, College of Veterinary & Animal Sciences, Parbhani for various surgical interventions.
Preparation of Animals
In all the dogs under study food was withheld for twelve hours and water withheld for eight hours prior to surgery. Weighing of each dog was done for calculating the exact dose of the anaesthetic agent prior to administration. All the animals were subjected to clinical examination prior to surgery and physiological parameters were recorded as reference.
Anaesthetic protocol
All the 14 clinical cases were randomly divided into two groups each consisting of seven dogs. All the dogs in study administered with inj. Atropine sulphate1 @ 0.04 mg/kg body weight subcutaneously. Group A: After administration of Atropine sulphate, 10 min later combination of Inj. Dexmedetomidine HCL (10 µg/kg body weight) and Inj. Butorphanol tartarate (0.2 mg/kg body weight) mixed in single syringe was administered intravenously. Group B: After administration of Atropine sulphate, 10 min later combination of Inj. Dexmedetomidine HCL (10 µg/kg body weight) and Inj. Midazolam maleate (0.2 mg/kg body weight) mixed in single syringe was administered intravenously. The sedation was assessed after the administration of drug combination (DB/DM) in both the groups. The grading of sedation was done depending upon the quality as described by Rauser and Lexmaulova, (2002) [17] . After the onset of sedation, inj. Propofol was given till the effect to get the surgical stage of anaesthesia and required amount was calculated as induction dose. Intermittent dosage for the maintenance of anaesthesia were given when required.
Haematological parameters
All the blood samples were collected from (cephalic/sephanous) veins aseptically. For haematological studies, blood samples collected in EDTA vials activator before anaesthesia (BP), during sedation (AP), during surgery (DS) and 24 hours after recovery (AR) from anaesthesia from both the groups. Haemoglobin (gram%), Packed cell volume (percentage), Total erythrocyte count (x10 6 /cumm), Total leucocytic count (x10 3 /cumm) were recorded.
Biochemical parameters
For biochemical estimation, the serum samples were separated from blood samples, collected in clot activator before preanaesthetic administration, after sedation, during surgery and after recovery from anaesthesia from animals of both the groups. Blood urea nitrogen (mg/dl), Blood creatinine (mg/dl), Blood glucose (mg/dl), Alanine transaminase (IU/dl), Aspartate transaminase (IU/dl) were recorded.
Statistical analysis
The data collected in the present study of different parameters were analyzed by conventional tools for data analysis (twoway ANOVA and 't' test) using WASP (Anonymus, 2018 WASP version 2.0 http://www.ccari.res.in/wasp2.0/index.php Last assessed on 4 August 2018).
Results
Results
Haematological parameter Haemoglobin
The mean ± SE values of haemoglobin in group A and group B are 13.18 ± 0.80 and 11.72 ± 0.91, respectively. As shown in Fig. 1, comparision within the group revealed that a nonsignificant decrease in Hb values was recorded in the animals of group A till sedation from baseline. However, the values were significantly decrease (P<0.05) during anaesthesia till recovery after 24 hours. In group B significant decrease (P<0.05) was observed during sedation and thereafter a nonsignificant decrease was observed till recovery after 24 hours. Comparison among both groups revealed significant difference (P<0.01) in Hb values at different interval before preanaesthetic, during sedation, during anaesthesia and at recovery 24 hours in both the groups. Overall significant difference (P<0.01) was observed between the groups.
Packed cell volume
The mean ± SE values of packed cell volume in group A and group B are 13.18 ± 0.80 and 11.72 ± 0.91, respectively. As shown in Fig 2, comparision within the group revealed that a significant decrease (P<0.01) in PCV values was recorded in the animals of group A thereafter non-significant increase was observed during anaesthesia and 24 hour after recovery. In group B, a non-significant decrease was observed during sedation and thereafter it was non-significantly decreased till recovery after 24 hours.
Total leucocyte count
The mean ± SE values of total leucocyte count in group A and group B are 12.10 ± 1.62 and 13.00 ± 2.15, respectively. As shown in Fig 4, comparision within the groups revealed that a non-significant decrease in TLC values was observed in the group A from baseline till during anaesthesia thereafter nonsignificant increase observed at recovery after 24 hour. In group B, a non-significant decrease was observed during sedation from baseline and thereafter a non-significant increase was observed till recovery after 24 hours.
Biochemical parameter Blood urea nitrogen
The mean ± SE values of blood urea nitrogen in group A and group B are 20.17 ± 1.52 and 18.73 ± 1.14, respectively. As shown in Fig 5, comparision within the groups revealed that a non-significant decrease in BUN values was observed in group A during sedation thereafter it was non-significantly increased till recovery after 24 hour. In group B, a nonsignificant increase was observed during sedation from baseline, thereafter it was significantly increased (P<0.05) during anaesthesia and non-significantly decreased till recovery after 24 hours.
Blood creatinine
The mean ± SE values of blood creatinine in group A and group B are 0.70±0.09 and 0.81 ± 0.09, respectively. As shown in Fig 6, comparision within the groups revealed that a significant increase (P<0.01) in blood creatinine values was observed in group A during sedation thereafter it was nonsignificantly decreased and then it was increased at the interval of during anaesthesia and 24 hours after recovery, respectively. In group B, a significant increase (P<0.05) was observed during sedation from baseline and thereafter it was non-significantly decreased and significantly increased (P<0.01) at the interval of during anaesthesia and recovery after 24 hours, respectively. Comparison among both groups revealed non-significant difference in blood creatinine values at the interval of before preanaesthetic and during sedation whereas significant difference (P<0.05) during anaesthesia level and thereafter significant difference (P<0.01) at during recovery after 24 hours was observed in between groups. Overall a nonsignificant difference was observed between the groups.
Blood glucose
The mean ± SE values of blood glucose in group A and group B are 79.61 ± 6.77and 82.85 ± 12.18, respectively. As shown in Fig. 7, comparision within the groups revealed that a non-significant increase in blood glucose values was recorded in group A at the interval of before preanaesthetic and during sedation thereafter significant increase (P<0.01) at interval of during anaesthesia and non-significant decrease during recovery. In group B, similar findings was observed up to interval of during anaesthesia thereafter followed significant decrease (P<0.05) at recovery after 24 hours. Comparison among both groups revealed non-significant difference in blood glucose values any interval in the animals of both groups. Overall a nonsignificant difference was observed between the groups.
Alanine transaminase
The mean ± SE values of alanine transaminase in group A and group B are 45.42 ± 5.70 and 56.39 ± 6.77, respectively. As shown in Fig 8, comparision within the groups revealed that a non-significant increase in ALT values was recorded in group A up to interval of during anaesthesia from baseline thereafter significant increase (P<0.05) was observed 24 hours after recovery. In group B, a non-significant increase was observed up to during sedation from baseline and thereafter it was increased significantly (P<0.01) and decreased significantly at interval of during anaesthesia and at recovery after 24 hours, respectively. Comparison among both groups revealed significant difference (P<0.05) in ALT values at the interval of before preanaesthetic and followed by significant difference (P<0.01) during sedation, during anaesthesia level and at during recovery after 24 hours was observed in between the animals of both groups. Overall a nonsignificant difference was observed between the groups.
Aspartate transaminase
The mean ± SE values of aspartate transaminase in group A and group B are 38.12 ± 5.62 and 45.39 ± 5.10, respectively. As shown in Fig 9, comparision within the groups revealed that a non-significant increase in AST values was observed in group A up to interval of during anaesthesia from baseline thereafter significant increase (P<0.05) was observed 24 hours after recovery. In group B, a non-significant increase was observed in all interval within the group.
Discussion
The decrease in haemoglobin levels might be due to due to shifting of fluids from the extravascular compartment to the intravascular compartment in order to maintain the cardiac output in the animals, haemodilution in response to fluid therapy and due to dexmedetomidine which has been shown to preserve blood flow to the most vital organs (brain, heart, liver and kidne y) at the expense of organs like skin and pancreas. Similar findings observed by Jena et al. (2014) [9] and Sethi et al. (2017) [22] . The decrease in PCV levels might be due to due to shifting of fluids from the extravascular compartment to the intravascular compartment in order to maintain the cardiac output in the animals, haemodilution in response to fluid therapy and 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. Similar findings observed by Jena et al. (2014) [9] and Sethi et al. (2017) [22] . This might be due to pooling of red blood cells in the spleen during early stage of anaesthesia. Similar findings were observed by Ozaydin et al. (2001) [16] , Jain et al. (2004) and Dewangan et al. (2016) [5] in dogs. The administration of α2-agonists suppresses the circulating catecholamines by exerting a modulating effect on leukocyte subpopulations (Kaname et al., 2002) [10] . Similar findings observed by Jena et al. (2014) [9] and Sethi et al. (2017) [22] . The increase in urea nitrogen values might be attributed to the temporary inhibitory effects of anaesthetic drugs on the renal blood flow, which in turn might have caused a rise in plasma urea nitrogen level. The increased hepatic urea production from amino acid degradation could also account for the observed increase in blood urea values during the maximum depth of anaesthesia. However, it is difficult to describe this to possible renal damage, because all the reported values were within normal physiological limits. Similar findings was observed by Surbhi et al. (2010), Santosh et al. (2011) [19] and Jena et al. (2014) [9] . The increase in plasma creatinine values might be attributed to the temporary inhibitory effects of anaesthetic drugs on the renal blood flow as reported in goats (Kinjavdekar et al., 2000) [12] and sheep (Monsang, 2011) [15] . The increase in blood glucose observed in the present study might be attributed to an α2-adrenergic inhibition of insulin released from beta cells of pancreas and increased glucose production in the liver. Hyperglycemia might also be attributed to the traumatic stress or increased muscular activity and sympathetic stimulation caused by restraining the animals resulting into increased secretion of adrenocortical hormones (Mirakhur et al., 1984). Similar findings was observed by Kinjavdekar et al. (2000) [12] , Surbhi et al. (2010) and Jena et al. (2014) [9] . 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) [21] . Similar findings was observed by Kanto and Gepts, (1989) [11] and Chandrakala et al. (2017) [4] . Non-significant increase in AST level might be associated with increased cell membrane permeability in response to haemodynamic changes induced by anaesthetic agents in xylazine-butorphanol-propofol in dogs (Chandrakala et al., 2017) [4] .
Conclusion
From the present study it could be concluded that intravenous administration of dexmedetomidine-butorphanol and dexmedetomidine-midazolam both as preanaesthetic combinations with propofol anaesthesia could be indicated as per the clinical demand in dogs without alarming changes in important physiological and haematobiochemical parameters if so they are transient without affecting the normal physiology, liver and kidney functions.
Figures and tables from the paper
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