Comparison of bupivacaine, xylazine and buprenorphine with ketamine combination for spinal analgesia in buffalo calves

Aim: The study was undertaken to compare the clinical efficacy of lumbosacral spinal analgesia produced using bupivacaine, xylazine and buprenorphine with ketamine combination in buffalo calves Materials and Methods: 36 male buffalo calves of seven to eight months of age and weighing 60 to 75 kg were used to evaluate the efficacy and safety of lumbosacral spinal analgesia produced by bupivacaine 0.25mg/kg, xylazine 0.05 mg/kg and buprenorphine 20 µg/kg in combination with ketamine 2.5mg/ kg and divided into groups A, B and C, respectively with 12 animals in each group. Results: The onset of analgesia in animals of group A (bupivacaine + ketamine) was 3.0±0.3 min, group B (xylazine + ketamine) was recorded as 2.6±0.4 min and group C (buprenorphine + ketamine) 4.0±0.4 min. Ketamine-bupivacaine in animals of group A produced complete analgesia of almost all the dermatomes for varying lengths of time. So also the group B except that it produced only moderate analgesia of thorax, abdomen and flank. Animals of group C produced only mild analgesia of thorax, abdomen and flank and moderate analgesia of digits , perineum, inguinal, himd limbs and tail region. The longest (>180 min.) duration of complete analgesia was recorded in animals of group A. The heart rate and respiration rate significantly decreased in group A and B than group C, so also the rectal temperature. Sedation recorded was maximum in group B fallowed by group A and least sedation scores were given by group C animals. Similiarly the scores of motor incordination was higher in group B and group A than group C. Conclusion: It was concluded that the combinations viz. Bupivacaine+ Ketamine and Xylazine + ketamine when given intraspinally at the lumbosacral space have similar analgesic potency on spinal administration in buffaloes. The synergism is more pronounced in xylazine-ketamine combination,whereas Buprenorphine +ketamine combination in the above said dose is a poor analgesic agent when used intraspinally at the lumbosacral space in buffalo calves.


post-traumatic analgesia and for laparotomy in goats [3]. Since general anaesthetics affect cardiovascular
Xylazine, an alpha -2 agonist, has been used to system in animals, general anesthesia should thus be induce sacrococcygeal/lumbosacral spinal analgesia avoided in patients with increased blood urea nitrogen in different species of animals and produces a longer level [1].Local and regional anesthesia would be a duration of regional analgesia [5,6].Epidural xylazine better choice in such patients.In this study three drugs produced a significantly greater duration of analgesia, (long acting nature) of different classes were selected in adult Holstein cows than did epidural lidocaine.The viz; long acting local anesthetic, alpha-2-agonist and incidence of ataxia associated with the use of xylazine an opioid: they were respectively combined with would also be expected to be less than lidocaine.ketamine to attain synergistic effect.
Further, when xylazine, given epidurally, produced Epidural analgesia produced by bupivacaine or greater perineal analgesia than did xylazine given xylazine has been reported to effectively reduce post intramuscularly [7].operative pain in goats.[2,3] and human beings [4].
It has been shown in a number of species that Bupivacaine, has been used in for preemptive, and opioids produce selective caudal epidural analgesia, by activating specific spinal receptors.Epidural with ketamine 2.5 mg/ kg at the lumbosacral space opioids have been used since long in human beings for using a 18 gauge, 7.5 cm spinal needle under aseptic conditions.Total quantity of injectable solution was relieving of post-operative pain.Buprenorphine is a made up to 6 ml by addition of normal saline solution partial mu opioid agonist and a strong kappa in each group.antagonist with long duration of action.It has a very wide margin of safety [8].NMDA receptor antagonists Observations: The animals were observed for appears to inhibit the neural plasticity underlying clinical and physiological parameters.Onset of some forms opiate tolerance, sensitization and physical analgesia was determined by recording the response to dependence, suggesting that NMDA receptors are skin pinpricks, using a 24-SWG made in the perineal involved in the develpment of these drugs induced region on either side of midline about 4-5 centimeters changes in behaviour [9].
below the anus after wiping off with cotton swab Ketamine has been used to enhance the depth of soaked in spirit.A strong avoidance response epidural analgesia produced by xylazine in animals manifested by kicking, quick shifting of weight on the and that produced by local anaesthesia in human hind limbs, rapid tail movements or turning and beings.Further, ketamine has been reported to have shaking of the head was considered as the normal least cardiopulmonary effects when used epidurally.response of the animal towards the stimulus.The time The present study therefore, was designed to evaluate from the spinal injection to the time of diminished and compare the utility of ketamine combination drugs response to pinprick stimulus was recorded as the time viz.Bupivacaine-ketamine, Xylazine-Ketamine and of onset of analgesia.The intensity of analgesia at the Buprenorphine-Ketamine to produce spinal analgesia.tail dorsal aspect, perineum both sides of the midline,

Materials and Methods
inguinal region, the upper parts of the hind limbs medial and lateral aspects of the thighs, the digits just 36 non-descript male buffalo calves of 7-8 months distal to fetlock, flank three sites on the lateral of age , weighing from 60-75 kg were equally divided abdominal wall; caudal, middle and cranial, ventral into 3 groups of 12 animals each, designated as groups abdomen three sites; caudal, middle and cranial and A, B and C. The animals were dewormed and vaccinated the thorax at the level of each rib starting from the last against important infectious and contagious diseases rib was determined by recording the response of the HS and FMDV and were maintained under uniform animals to pinpricks at these sites.The depth of managemental conditions.The animals were kept off analgesia at the different sites was graded by feed for 24 hours and water was withheld 12 hours observing the response of the animal to the pinpricks prior to the start of the experiment.The Animal Ethics on a 0 to 3 scale using a scoring system as given in Committee of the Indian Veterinary Research Table 1 below.Depth of analgesia was recorded at 0, 5, Institute, Izatnagar, India, approved the study.The 10, 15, 20, 30, 45, 60, 75, 90, 105, 120, 130, 150 and animals were restrained in standing position with 180 minutes after injection of drugs.cotton rope halters in a cattle crush.The lumbosacral space was palpated and the area of injection was Ataxia and sedation: Ataxia and sedation was clipped, shaved and painted with povidone iodine for graded on a 0 to 3 scale using a scoring system as given aseptic spinal injection.An initial weal was produced in Table 1. with 2% lignocaine hydrochloride using a fine needle Duration of analgesia: The time from the loss of at the center of lumbosacral space.In group A sensation at the perineum to the time of return of full bupivacaine 0.25mg/kg, in group B, xylazine 0.05 sensation at all the sites was considered as the duration mg/kg, in group C buprenorphine 20 µg/kg was administered intraspinally respectively in combination of analgesia.phase of sedation showed significantly higher (P < 4b).Heart rate: A significant (P<0.05)decrease in the Rectal temperature: Group A and Group B heart rate was recorded in group A animals throughout however, showed a significant (P < 0.05) decrease in the observation period starting from 30 min of spinal rectal temperature throughout the period of injection.In the animals of group B also, a significant observation.The rectal temperature was significantly (P<0.05)decrease in the heart rate from 10-60 min was lower in group B than other groups.Group C animals, recorded and continued to be lesser than the base line showed a non-significant (P > 0.05) change in rectal till the end of observation period.In group C animals temperature (Fig 4c).no significant (P>0.05)change in heart rate was Discussion recorded throughout the observation period.

Comparison among groups revealed that depression in
The early onset of analgesia, complete analgesia heart rate was most significant (P<0.05) in group B of most of the regions and prolonged duration of than other groups (Fig 4a).
analgesia in group A and B as compared to the group C Respiratory rate: Group A animals, showed a which did not attain complete analgesia of any region significant (P < 0.05) decrease in the respiration rate was probably due to the fact that α--adrenoceptor  recorded an antagonistic interaction between epidural agonists is associated with the activation of central α -2 pethidine and ketamine in dogs.Recovery from the adrenoceptors, which causes decrease in the release effects of different drugs was in the order as group C and turnover of norepinephrine in the CNS.The followed by group A followed by group B. Reduction sedative effects of epidural administration of xylazine in HR after epidural/spinal administration of are due to the systemic effect of the drug after bupivacaine has been reported in dogs [23], goats [24], absorption through longitudinal epidural veins and and buffalo [25], the decrease in HR was significantly possibly the lymphatics [14].Comparable degree of more in group B than other groups.sedation was reported following spinal injection of No appreciable change in heart rate was xylazine alone or ketamine and xylazine combination observed after spinal administration of buprenorphine in cattle [15] Frequent urination was noticed in most of in combination with ketamine.Buprenorphine being the animals after administration of α -agonist alone 2 more lipophillic gets less absorbed into vascular/ and in combination with ketamine.This might be due lymphatic circulation from subarachnoid space [26].to inhibition of production and release of ADH, due to Buprenorphine i.v. or i.m did not produce alterations paralysis of sympathetic nerves to the sphincter of the in the cardiovascular parameters that could provide bladder could also have been a cause of micturition as any significant clinical effects in dogs [27].reported by.Diuresis was also observed with Buprenorphine was shown to have a ceiling effect for medetomidine and xylazine in dogs [15].Increased respiration rate but not analgesia [28].urinary output following xylazine [16].Group A Group A and B also showed a decrease in the (Ketamine + bupivacaine) animals remained less respiration rate which was significant in group A and sedated throughout the period of observation.The non significant in group B but the animals of group C finding was coherent with the observations of showed an increase in the respiration rate.The results Kinjavdekar, 1998 [17] and Locatelli et al., 1997 [18], suggested that ketamine in group A failed to counteract following spinal administration of ketamine.group C the respiratory depressant action of bupivacaine.It (ketamine + buprenorphine) animals, only a mild could be due to the fact that bupivacaine induced the degree of sedation with slight ptosis of eye lids was decrease in RR through the blockade of nerves observed.The mild sedation was also accompanied innervating the muscles of respiration as suggested by with marked euphoria in the animals of group C Rayees et al, 2011 [29].On the other hand, in group B throughout the period of observation.This euphoria the respiratory depression produced by xylazine could was manifested as paddling of limbs, pressing of head be well balanced by predominant stimulatory effect of against wall and hitting the head continuously to ketamine which balanced the CNS depressant effect α ground wall.Similar finding was reported in cats with -2-agonists [30].The elevated RR in animals of group i.m buprenorphine [19].Opioid induced sedation was C might have been mainly due to the stimulatory effect reported not to increase further when combined with of ketamine on the respiratory centres.Buprenorphine ketamine, this might have explained comparatively has been reported to have a "ceiling effect" on lesser duration of sedation in group C. Further cardiopulmonary depression [8,31].buprenorphine is lipophillic and its delayed effect is In group A and B, Rectal temperature reduced usually related to slow receptor binding which occurs significantly for longer duration but showed nonwith partial agonists.significant increase in group C. The decrease in RT In group A animals, an extreme incoordination might be due to generalized sedation, decrease in

Physiological Parameter:
Heart rate, Respiration Ketamine-bupivacaine in animals of group A rate and rectal temperature were also recorded on the produced complete analgesia of digits, perineum, above intervals.inguinal region, abdomen, hind limbs, tail and flank region and moderate analgesia of thorax for varing Statistical analysis: Analysis of variance and lengths of time (Fig 1 and Fig 2).Ketamine-xylazine in Duncan's multiple range test were used to compare the animals of group B produced moderate analgesia of data of parametric observations at different intervals thorax, abdomen and flank and complete analgesia of between the groups.Paired t-test with Bonferroni digits, perineum, inguinal region, hind limbs and tail.correction was used for comparison of mean ± SE at Ketamine-buprenorphine in animals of group C different time intervals with the base values of the produced only mild analgesia of thorax, abdomen and respective treatments as per the standard procedures of flank and a maximum of moderate analgesia of digits, Snedecor GW & Cochran WG 1967.Kruskal -Wallis's perineum, inguinal region, hind limbs and tail region.one way test was used to compare the means among Analgesia in group A and B didn't differ significantly the groups of non-parametric observations.The values (P>0.05) from each other but analgesia weaned off in were considered as significant at P<0.05 and P<0.01. group B at 150 min and continued to persist at Results moderate level in group A, throughout the observation period.The longest (>180 min.)duration of complete The onset of analgesia in animals of group A analgesia was recorded in animals of group A. (bupivacaine + ketamine) was 3.0±0.3min, group B (xylazine + ketamine) was recorded as 2.6±0.4 min Sedation recorded: Comparison between A, B and C and group C (buprenorphine + ketamine) 4.0±0.4min.groups shows that, Group A animals showed The total duration of analgesia in group A and B was significantly higher (P < 0.05) sedation from 60 to 180 more than 180 min.min post injection, as compared to group C, similarly group B (ketamine-xylazine) animals, after a mild Summary of depth and extent of analgesia: