Physiologic and biochemical effects of subarachnoidally
administered xylazine and medetomidine in goats
P. Kinjavdekar
*, G.R. Singh Amarpal, H.P. Aithal, A.M. Pawde
Division of Surgery, Indian Veterinary Research Institute, Izatnagar 243 122 (UP), India
Received 10 March 1999; accepted 18 April 2000
Abstract
Clinicophysiological, haematological and biochemical effects of xylazine (0.05 mg kgÿ1) and medetomidine
(0.01 mg kgÿ1
) were studied in nine adult goats after lumbosacral subarachnoid administration. The onset of analgesia by xylazine and medetomidine was observed in 9.111.07 and 8.662.37 min (meanS.E.), respectively. Both a2-agonists produced moderate analgesia of hind quarter, perineum and ¯ank, mild ataxia and sedation. The duration of analgesia after xylazine administration was 134.448.87 min and that after medetomidine was 158.339.96 min (meanS.E.). Xylazine and medetomidine induced signi®cant (p<0.05) decrease in heart rate, respiratory rate and hypothermia. Haemoglobin (Hb), packed cell volume (PCV) and total leukocyte count (TLC) decreased signi®cantly. Changes in the physiological and haematological parameters were transient in nature. Xylazine and medetomidine produced a signi®cant (p<0.05) increase in creatinine and glucose levels. However, these parameters ¯uctuated within normal range and started to recover within 120 min. However, serum urea nitrogen (SUN), serum chloride, sodium and potassium did not show any signi®cant change. The effects produced by xylazine and medetomidine were however, comparable at these dose levels. The study indicates that xylazine at 0.05 mg kgÿ1 and medetomidine at 0.01 mg kgÿ1 did not induce any serious alteration in the physiological,
haematological and biochemical parameters and can be safely used in inducing hind quarter, ¯ank and perineal analgesia in goats.#2000 Elsevier Science B.V. All rights reserved.
Keywords:Spinal anaesthesia; Goats; Xylazine; Medetomidine
1. Introduction
Xylazine and medetomidine are two,a2-adrenergic receptor agonists. Thea2/a1-receptor binding selec-tivity indicates that medetomidine is more selective and speci®ca2-adrenergic receptor agonist than xyla-zine (Virtanen, 1989). Among all domestic animals ruminants are the most sensitive to xylazine . In recent years xylazine has been used epidurally in many
species of animals. Although 2% lidocaine hydro-chloride is the most commonly used drug for this purpose, studies have indicated that xylazine induces analgesia of the perineum when administered epidu-rally in horses (LeBlanc et al., 1988); ponies (Fikes et al., 1989) and cattle (Jean et al., 1990). Those studies indicate that xylazine provided analgesia that was longer in onset and duration than did the more conventional epidural administration of lidocaine. In goats very little information about the analgesic, cardiovascular and respiratory effects of subarach-noidally or epidurally administered xylazine is avail-able. Previous studies (Aithal et al., 1996) indicated *Corresponding author. Tel.:91-581-442870-(0);
fax:91-581-457284-447179
E-mail address: ivri@x400.nicgw.nic.in (P. Kinjavdekar).
that xylazine at 0.05 mg kgÿ1
administered into the lumbosacral epidural space induced safe hind quarter analgesia in goats. Medetomidine being a more selec-tive a2-adrenoceptor agonist than xylazine has been used epidurally in cats (Duke et al., 1994a). To the authors' knowledge, the safety of subarachnoid administration of medetomidine in goats has not been reported. In addition, reports of comparative effects of lumbosacral subarachnoidally administered xylazine and medetomidine on analgesic, cardiovascular and respiratory systems, head ptosis, position of pelvic limbs and sedation are lacking. In the present study, we determined and compared the analgesic, physio-logic, haematologic and biochemical effects in response to xylazine at 0.05 mg kgÿ1
and medetomi-dine at 0.01 mg kgÿ1
each diluted to a total volume of 2 ml with 0.9% normal saline and administered into the lumbosacral subarachnoid space in healthy goats.
2. Materials and methods
Nine non-descript adult goats of either sex weighing 15±25 kg were used in this study. The animals were apparently healthy and dewormed 1 month before the start of the experiment. The animals were stall fed and had free access to feed and water. The animals were kept off feed for 24 h and water was withheld for 12 h prior to the start of the experiment. During the course of trials the ambient temperature ¯uctuated between 38 and 398C. The animals were assigned randomly in two groups. Nine trials each of the two treatments (forming two groups) were carried out in these nine animals keeping a gap of 1 week between each trial using one animal twice only. Freshly prepared solu-tions of xylazine at 0.05 mg kgÿ1or medetomidine at 0.01 mg kgÿ1 were diluted to 2 ml using 0.9% phy-siologic saline solution. The dose rates of xylazine and medetomidine were determined after conducting pilot trials in a few goats. In these trials it was observed that after increasing the dose rates of both a2-agonists, from the one used in this study, the depth of analgesia remained the same in all the dose rates tested, while sedation increased. Therefore, the dose rates of xylazine (0.05 mg kgÿ1
) and medetomidine (0.01 mg kgÿ1
) were selected. The animals were restrained in standing position. The lumbosacral region was clipped, shaved and painted with povidone
iodine solution. A 20 gauge, 2.5 cm long hypodermic needle was placed into the subarachnoid space at the lumbosacral intervertebral space. The needle was directed to a 60 to 758angle to the spinal cord along the median plane and was slowly advanced until the lumbosacral subarachnoid space was reached after penetrating the interarcuate ligament and dura mater. Correct position of needle was ascertained by free ¯ow of CSF from the needle hub. The drug was then injected.
The base line values (time0) for physiological and clinical parameters were made before injection of drug. Blood samples were also collected at time zero before drug administration. The two treatments were evaluated and compared on the basis of clinical, physiologic, haematologic and biochemical para-meters. The investigator for the subjective determina-tion of scores for analgesia, sedadetermina-tion and hind limb ataxia was not blinded but was the same person during each trial throughout the period of study. Onset of analgesia was recorded at perineal region using pin prick method. Depth of analgesia was recorded from the response shown by the animal at a particular region by pin pricks. Pin pricks were made at tail, perineum, udder/scrotum, thigh, digits, ¯ank and thorax at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 min post-injection and graded in a scale of 0±3, where 0 represents no analgesia Ð strong reaction to pin pricks, 1, mild analgesia Ð weak response to pin pricks, 2, moderate analgesia Ð occasional response to pin pricks, 3, strong/complete analgesia Ð no response to pin pricks.
duration of analgesia (time from loss to return of sensation) perineal region was considered as the area where pin prick response was recorded till zero score/ return of sensation was achieved up to 120 min or even beyond that. Physiological parameters such as heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were also recorded at the same time intervals after injection of the drug. Blood samples were col-lected in clean, dry vials containing EDTA before and at 30, 60, 120 min and 24 h after injection of drug for estimation of haemoglobin (Hb), packed cell volume (PCV) and total leukocyte count (TLC). Blood sam-ples were also collected in clean, dry test tubes at the same intervals for separation of serum to estimate serum urea nitrogen (SUN), creatinine, glucose, chlor-ide, sodium and potassium. Data were subjected to paired `t' test for comparison of means and students `t' test for comparison of means of two treatments (Sne-decor and Cochran, 1967).
3. Results
The body weight of animals were 193.2 kg (meanS.E.). Absence of response to pin pricks at perineal region provided satisfactory indication for the onset of analgesia. The onset of analgesia by xylazine and medetomidine was observed in 9.111.07 and 8.662.37 min (meanS.E.), respectively (Fig. 1). Response to pin pricks also provided satisfactory
indication regarding the depth of analgesia in different body regions during the post-injection period. Zero to 3 grading could help in quantifying the absence of analgesia, mild, moderate and complete analgesia, respectively at a particular region.
Depth and extent of analgesia produced by xylazine and medetomidine was mild to moderate at hind quarter, perineum, ¯ank and thorax (Figs. 2±4). The analgesia was mild at tail, udder/scrotum and digits of hind limbs. Medetomidine produced comparatively longer duration (90±105 min) of mild to moderate analgesia of hind quarter, ¯ank and thorax, in com-parison to xylazine (75±90 min) (Figs. 2±4). Though the difference between two treatments was non-sig-ni®cant. Animals of both treatment groups were able to stand during the post-injection period. While walk-ing they showed mild ataxia throughout the period of observation (Fig. 5). Xylazine and medetomidine did not show sedation for the ®rst 5±10 min after injection of the drug. The animals were standing but appeared tired, indicating mild degree of sedation until the end of observation (Fig. 6). Duration of analgesia at perineal region was recorded up to 120 min or beyond that, since in many instances the pin prick response showed analgesia beyond 120 min. The duration of analgesia after xylazine administration was 134.44 8.87 min and that after medetomidine was 158.33 9.96 min. The total duration of analgesia at perineal region was comparable between the two treatment groups (Fig. 7). When the animals were completely
Fig. 2. Hindquarter analgesia (meanS.E.) after subarachnoid administration of xylazine and medetomidine in goats.
Fig. 3. Perineal analgesia (meanS.E.) after subarachnoid administration of xylazine and medetomidine in goats.
Fig. 5. Ataxia (meanS.E.) after subarachnoid administration of xylazine and medetomidine in goats.
Fig. 6. Sedation (meanS.E.) after subarachnoid administration of xylazine and medetomidine in goats.
alert and had normal gait with absence of analgesia in the perineal region, it was considered to have recov-ered from the effects of the drug. Recovery time was similar to that of duration of analgesia.
Both a2-agonists, caused a signi®cant (p<0.05) decrease in HR 5 min after subarachnoid injection of the drug. It persisted signi®cantly (p<0.05) lower in subsequent intervals and the values at 75 min in xylazine group and 90 min in medetomidine group were the lowest (Fig. 8). Even at the end of observa-tion period the values remained signi®cantly (p<0.05)
lower than the base values. The difference was non-signi®cant (p>0.05) between the two treatment groups at any interval. Xylazine caused a signi®cant (p<0.05) decrease in RR 5 min after subarachnoid administra-tion, whereas medetomidine caused a non-signi®cant (p>0.05) decrease 10 min after subarachnoid injec-tion, in subsequent intervals. Further signi®cant (p<0.01) decrease in RR was recorded in both groups and the lowest values with xylazine were recorded at 60 min and with medetomidine at 105 min (Fig. 9). Thereafter, slight improvement in RR was seen but the
Fig. 8. MeanS.E. of heart rate (beats per min) after subarachnoid administration of xylazine and medetomidine in goats. *Signi®cantly different from the base value (p<0.05), **Signi®cantly different from the base value (p<0.01).
values remained signi®cantly (p<0.01) lower than the base values. A non-signi®cant (p>0.05) decrease in RT was observed at 5 and 20 min after injection of xylazine and medetomidine, respectively. In subse-quent intervals a signi®cant (p<0.05) decrease was recorded with xylazine, however, a non-signi®cant (p>0.05) decrease persisted with medetomidine throughout the period of observation (Fig. 10).
A non-signi®cant (p>0.05) decrease in Hb values was recorded at 30 min after xylazine and medetomi-dine administration. Signi®cant (p<0.05) decrease was recorded in subsequent intervals in both groups (Table 1). Similarly, signi®cant (p<0.01) decrease in PCV was recorded in the post-injection period with botha2-agonists. However, at 24 h the values returned to the preadministration level in both groups. TLC also
Fig. 10. MeanS.E. of rectal temperature (8F) after subarachnoid administration of xylazine and medetomidine in goats. *Signi®cantly different from the base value (p<0.05).
Table 1
Effects of spinal xylazine and medetomidine in goats on haematological and biochemical parameters (meanS.E.)
Parameters Druga Baseline 30 min 60 min 120 min 24 h Haemoglobin X 110.004.49 107.784.65 107.334.00 107.783.64 108.893.61 (Hb) (glÿ1) M 109.443.86 105.003.33 101.673.73* 99.443.27* 106.113.41
Packed cell volume X 0.290.01 0.270.01** 0.260.01** 0.260.01** 0.280.01 (PCV) (LLÿ1) M 0.290.00 0.280.00** 0.260.01** 0.270.01** 0.290.01
Total Leukocyte count X 9.920.72 8.660.67 7.460.67** 7.380.95* 9.140.83 (TLC) (109lÿ1) M 10.980.41 8.540.43** 6.730.56** 7.210.79** 9.110.73* Serum urea nitrogen X 7.480.87 7.681.27 7.711.51 7.460.68 7.111.24 (mmol lÿ1) M 7.270.29 6.440.65 7.820.80 7.470.89 6.410.50 Creatinine X 93.141.97 112.503.35** 112.383.01** 121.242.76** 91.211.87 (mmol lÿ1) M 93.591.30 108.901.29** 112.603.63** 112.803.83** 93.711.78 Glucose X 4.841.50 8.601.68* 6.051.04 8.981.59 5.111.25 (mmol lÿ1) M 3.330.81 4.140.70 4.250.86 7.071.26** 3.940.97 Chloride X 102.553.82 103.783.66 102.903.85 102.333.31 101.364.59 (mmol lÿ1) M 98.961.99 100.384.38 102.083.91 100.235.41 100.194.50
Sodium X 148.221.13 149.221.12 143.783.28 147.561.78 147.112.88 (mmol lÿ1) M 146.111.84 145.561.99 144.112.77 147.782.68 147.112.31
Potassium X 5.460.42 5.810.35 4.810.50 5.630.56 5.320.41 (mmol lÿ1) M 6.010.33 5.590.33 6.190.37 5.870.32 6.240.44
aX, xylazine; M, medetomidine.
decreased signi®cantly (p<0.01) in both groups in the post-injection period. The values improved at 24 h but remained lower than the base values (Table 1).
The SUN values did not show any signi®cant change (Table 1). Xylazine and medetomidine pro-duced a signi®cant (p<0.01) increase in creatinine values post-injection up to 120 min. The values, how-ever, returned to the preadministration level at 24 h. Similarly, signi®cant (p<0.05) increase in serum glu-cose was recorded during the post-injection period. The values however, remained above the base line at 24 h (Table 1). Serum chloride, sodium and potassium values did not show a de®nite trend throughout the observation period (Table 1).
4. Discussion
The pin prick response method gave a satisfactory indication for ascertaining the onset and depth of analgesia. In comparison to local anaesthetics, xyla-zine or medetomidine produced a delayed response to onset of analgesia. A delayed onset of analgesia by xylazine in comparison to lignocaine has been reported in various animal species (Fikes et al., 1989; Grubb et al., 1992; Aithal et al., 1996). This has been attributed to the fact that the analgesia induced by xylazine is spinal cord mediated, whereas it is spinal nerve mediated in lignocaine (LeBlanc et al., 1988). Further, the onset of analgesia by xyla-zine and medetomidine as reported by earlier workers may be related to either species difference, level of injection (subarachnoid or epidural injection), site of injection (lumbosacral or sacrococcygeal), dose rate or a combination of these factors (LeBlanc et al., 1988; Fikes et al., 1989; Skarda and Muir, 1996). Xylazine , medetomidine in animals (Livingston et al., 1992) and dexmedetomidine in human beings (Cullen, 1996) have been reported to produce good spinal analgesia. In the present study, these agents also produced spinal analgesia of longer duration than lignocaine hydrochloride. It was probably due to the fact thata2-adrenoceptor agonists provide a local depot of the drug and are released slowly over a longer period of time (Nolan et al., 1987). Similar results were obtained by Grubb et al. (1992). The mechanism by which xylazine and medetomidine induce spinal analgesia was not investigated in this study.
Analgesia produced by xylazine was probably due to its local anaesthetic effects (Aziz and Martin, 1978), which inhibit impulse conduction in primary afferent nerve ®bres or of stimulation of a1- and a2 -adreno-ceptors in the spinal cord and CNS (Aziz and Martin, 1978), through inhibition of the release of neurotrans-mitters (Kuraishi et al., 1985) and decreased neuronal activity (Vainio, 1983). The primary site of antinoci-ceptive action ofa2-agonists after intrathecal admin-istration is ata2-adrenergic receptors in the substantia gelatinosa of the dorsal horn of spinal cord (Yaksh, 1985), where they inhibit the release of substance P, which is involved in pain sensation (Grubb et al., 1993). This is probably the area which modulates the response to noxious or mechanical cutaneous stimulation in various species (Fleetwood-Walker et al., 1985). By contrast analgesia induced by mede-tomidine might have been the result of its binding to
a2-adrenoceptors in the spinal cord (Vainio, 1983).These drugs have been reported to inhibit noci-ceptive responses when injected into the ®rst lumbar epidural space of sheep (Eisenach, 1992), lumbosacral epidural space in goats (Aithal et al., 1996) and ®rst intercoccygeal epidural space of horses (LeBlanc et al., 1988), ponies (Fikes et al., 1989) and cattle (Jean et al., 1990).
Depending on the drug, dose rate, volume and site of injection, a wide range of segmental analgesic zones were observed in animals after epidural or subarachnoid administration of a2-agonists (Fikes et al., 1989; Skarda and Muir, 1994). In the present study, xylazine and medetomidine produced qualita-tively equal degree of analgesia of hind quarter, ¯ank and thorax. We speculate that both drugs were absorbed from the subarachnoid space, thereby indu-cing general inhibition of sympathetic nervous system activity and re¯exes (Virtanen, 1986). Similar results were obtained by Muir et al. (1992) in horses, when they administered xylazine and detomidine epidurally. Comparatively longer duration of analgesia by mede-tomidine, though non-signi®cant, as compared to xylazine is due to dose dependency and may probably be due to its being more potent than xylazine and the pharmacokinetic differences between the two drugs that determines the half life or clearance of a drug.
1996). In the present study, this variable was kept uniform in all animals and therefore, any variation in the extent and depth of analgesia may be attributed to the potency of the drug itself. In this study, xylazine and medetomidine induced analgesia extended up to thorax anteriorly and digits of hind limbs. It has been reported that the distribution of anaesthetic solution in the CSF determines the uptake of anaesthetic. Further, uptake was found to be the greatest where the con-centration of solution was greatest (i.e. at the site of injection) and decreased above and below the site of highest concentration (Greene, 1983). It may there-fore, be hypothesized that higher degree of analgesia obtained at thigh and perineum in the present study may be due to the highest concentration of anaesthetic solution at the site of injection, i.e. lumbosacral epi-dural space from where the spinal nerves, which innervate these regions, originate.
Mild relaxation of tail and anal sphincter was seen in both xylazine and medetomidine groups. Relaxa-tion of anal sphincter along with relaxaRelaxa-tion of con-strictor vulvae muscle, rectum, bladder and genitalia has also been reported in cattle after epidural admin-istration of xylazine (Skarda and Muir, 1992). This may be attributed to blockade of autonomic and motor nerves as also reported by Skarda and Muir (1992) and Aithal et al. (1996).
Mild ataxia was apparent in the animals of both groups while walking throughout the period of obser-vation.a2-Agonists result in a selective blockade of sensory ®bres so that analgesia is achieved without hind limb dysfunction (Grubb et al., 1992). The ataxia produced by xylazine in the present study may be related to its postulated local anaesthetic action on hind limb motor neurons (LeBlanc et al., 1988) prob-ably due to structural similarity with lignocaine (Anto-naccio et al., 1973). Xylazine has been shown to have a local anaesthetic effect on frog sciatic nerve trunk preparations similar to that of 0.5% procaine hydro-chloride (Aziz and Martin, 1978). However, preva-lence of hind quarter ataxia was less in this study as compared to that produced by lignocaine (Grubb et al., 1992). Hind limb ataxia in medetomidine group might be due to its possible local action in the hind limb motor neurons (Skarda and Muir, 1994). It has been seen that a2-adrenergic antagonists effectively reversed sedation, but did not completely abolish analgesia and ataxia induced by
epidurally/subarach-noidally administered a2-agonist in horses (Skarda and Muir, 1994) further indicating at least a possible partial local analgesic spinal effect of a2-agonists. Since the dose of xylazine and medetomidine used in this study was much less as than in previous studies, only mild ataxia was noticed. However, a local anaes-thetic action of xylazine has been cited as the reason for ataxia when its dose exceeded 0.24 mg/kg (LeBlanc et al., 1988).
Sedation produced by xylazine or medetomidine was of mild degree. The animals appeared tired as indicated by drooping of head and eye lids. Salivation was noticed in most of the animals. This indicates that the drug was rapidly absorbed from the subarachnoid space and distributed to the brain. The sedative effects ofa2-agonists is associated with the activation ofa2 -adrenoceptors which causes decrease in the release and turnover of norepinephrine in the CNS (Jean et al., 1990). The onset of sedation started at about 10 min after the drug administration, i.e. much later than the onset of analgesia. This indicates that the analgesic action of the drug is mediated through spinal action rather than a central effect as also reported by Aithal et al. (1996) who also used xylazine at lumbosacral epidural space in goats. However, some workers have also reported that xylazine did not produce sedation in horses and donkeys (LeBlanc and Eberhart, 1990; Makady et al., 1991).
Frequent urination was noticed in most of the animals after administration of xylazine or medetomidine. This may be due to inhibition of production and release of ADH. In another study, increased urine production was attributed to the osmotic diuretic effect of increased blood glucose bya2-agonists (Duke et al., 1994a).
LeBlanc and Eberhart (1990) found no measurable change in cardiovascular parameters after caudal epi-dural administration of xylazine in horses. Respiratory rate also decreased in both groups ofa2-agonists and was comparable. Decrease in respiratory rate may be due to the direct depression of the respiratory centres (Kumar and Thurmon, 1979; Rings and Muir, 1982). Signi®cant decrease in respiratory rates was also observed after the administration of xylazine in cattle (Jean et al., 1990; Skarda and Muir, 1992); goats (Aithal et al., 1996); sheep (Waterman et al., 1987) and medetomidine in dogs (Vesal et al., 1996) and cats (Duke et al., 1994b). Signi®cant decrease in body temperature by xylazine might be due to a fall in the ambient temperature during the course of the trial. However, decrease in rectal temperature by xylazine or medetomidine may also be due to generalized sedation, decrease in metabolic rate, muscle relaxation and CNS depression.a2-Agonists have been reported to induce prolonged depression of thermoregulation (Ponder and Clarke, 1980). These agents also have been found to depress the hypothalamic nor-adrener-gic a2-receptors to cause hypothermia (MacDonald et al., 1988). Reduced basal metabolic rate and muscle activity on the one hand and depression of thermo-regulation on the other hand may result in hypother-mia (Ponder and Clarke, 1980). Further, the decrease in rectal temperature bya2-agonists is not only related to centrala2-adrenergic mechanisms (Livingston et al., 1984) but probably also related to other depressing CNS mechanisms, because hypothermia could not be prevented by prior administration of yohimbine (Vir-tanen, 1986).
Hb, PCV and TLC decreased after xylazine and medetomidine administration. Pooling of the circulat-ing blood cells in the spleen or other reservoirs secondary to decreased sympathetic activity may explain the decrease in Hb, PCV and TLC recorded in this study as also reported with other tranquilizers in dog (Solimon et al., 1965). The decrease in PCV and Hb during the period of anaesthesia or sedation may be due to shifting of ¯uid from extravascular compart-ment to intravascular compartcompart-ment (Wagner et al., 1991) in order to maintain normal cardiac output in the animal. However, while experimenting with deto-midine in horses, Gasthuys et al. (1987) observed an increase in PCV at 30 min of drug administration. This could be caused either by increased urine production
due to activation of capillary ¯uid shift mechanism or by the release of the splenic red blood cells reservoir (Kumar and Thurmon, 1978).
The ¯uctuations in creatinine values may be attrib-uted to a temporary inhibitory effect of the drug on renal blood ¯ow, which in turn might have caused a rise in creatinine. However, it is dif®cult to ascribe this to possible renal damage, because all the reported values were within normal limits. Hyperglycaemic effects of a2-agonists are well known. There have been many investigations into the hyperglycaemic effects of xylazine (Eichner et al., 1979; Hsu and Hummel, 1981) and medetomidine (Cullen, 1996). Hyperglycaemia observed in this study may be due to an a2-adrenergic inhibition of insulin release by stimulation of a2-receptors in the pancreatic b-cells (Angel and Langer, 1988) and to an increased glucose production in the liver (Hsu and Hummel, 1981). Though it is not clear from this study that the action of subarachnoid xylazine or medetomidine on liver and b-cells of pancreas is either direct or indirect. However, in the author's view it may be an indirect action since these drugs were absorbed from the subarachnoid space and thereby stimulated the a2 -adrenoceptors inb-cells and liver. However, Mirakhur et al. (1984) opined that hyperglycaemia may be due to rise in adrenocortical hormones during stress. A rapid and longer increase of blood glucose in xylazine group than medetomidine group in the present study might be due to the predominant action of xylazine on
a2-adrenoceptors inb-cells of pancreatic islets along witha1-adrenoceptor agonistic effects (Hsu and Hum-mel, 1981) as also seen in other ruminants (Brikas et al., 1987). However, we hypothesize that in mede-tomidine group a weak or nil a1-adrenoceptor ago-nistic effect might have produced a slow and transient increase of blood glucose. Serum electrocytes remained unaltered throughout the period of the study. The overall observation on blood biochemical para-meters suggested that the alteration seen in different parameters were the outcome of general stress pro-duced during the study as the changes were transient.
5. Conclusions
mede-tomidine (0.01 mg kgÿ1
) at lumbosacral space pro-duce selective sensory blockade of nociceptive ®bres lasting longer than 2 h, with minimal motor inhibition in conscious goats. Further experiments are needed to support the hypothesis that medetomidine also has a local analgesic action similar to that of xylazine. Both drugs caused mild sedation, ataxia, mild cardiopul-monary depression and renal diuresis. The haemato-logical and biochemical alterations produced by these drugs were transient in nature and returned to normal levels as the effects of these drugs weaned off. The haematological changes were due to temporary shift-ing of ¯uid from extravascular compartment to the intravascular one. Similarly, alterations in biochem-ical indices were due to generalized stress produced by these drugs. The effects produced by xylazine and medetomidine were however, comparable at these dose levels. Therefore, both drugs can be safely used for inducing analgesia of hind quarter, ¯ank and perineum.
Acknowledgements
The authors are thankful to Dr. Outi Vainio, Research Manager, Farmos Group, Turku, Finland for ample supply of Domitor (Medetomidine hydro-chloride) for the present study.
References
Aithal, H.P., Amarpal, Pratap K., Singh, G.R., 1996. Clinical effects of epidurally administered ketamine and xylazine in goats. Small Rumin. Res. 24, 55±64.
Angel, I., Langer, S.Z., 1988. Adrenergic induced hyperglycaemia in anaesthetised rats: involvement of peripheral,a2
-adrenocep-tors. Eur. J. Pharmacol. 154, 191±196.
Antonaccio, M.J., Robson, R.D., Kerwin, L., 1973. Evidence for increased vagal tone and enhancement of baroreceptor re¯ex activity after xylazine in anaesthetized dogs. Eur. J. Pharmacol. 23, 311±315.
Aziz, M.A., Martin, G.J., 1978. Alpha agonist and local anaesthetic properties of xylazine. Zentralbl Veterinarimed (A) 25, 181±188. Brikas, P., Tsiamitas, C., Ayiannidis, A., 1987. Xylazine induced hyperglycaemia and a-adrenergic receptors in sheep. J. Vet. Med. (A) 34, 58±60.
Cullen, L.K., 1996. Medetomidine sedation in dogs and cats: a review of its pharmacology. Br. Vet. J. 152, 519±535. Duke, T., Cox, A.K., Remedios, A.M., Cribb, P.H.,
Komulainen-Cox, A.M., 1994a. The analgesic effects of administering
fentanyl or medetomidine in the lumbosacral epidural space of cats. Vet. Surg. 23, 143±148.
Duke, T., Cox, A.K., Remedios, A.M., Cribb, P.H., 1994b. The cardiopulmonary effects of placing fentanyl or medetomidine in the lumbosacral epidural space of iso¯urane anesthetized cats. Vet. Surg. 23, 149±155.
Eichner, R.D., Proir, R.L., Kvascnicka, W.G., 1979. Xylazine-induced hyperglycaemia in beef cattle. Am. J. Vet. Res. 40, 127±129.
Eisenach, J.C., 1992. Intraspinal a2-adrenergic analgesia in
sheep. In: Short, C.E., Poznak, A.V. (Eds.), Animal Pain. Churchill Livingstone, New York, pp. 277±280.
Fikes, L.W., Lin, H.C., Thurmon, J.C., 1989. A preliminary comparison of lidocaine and xylazine as epidural analgesics in ponies. Vet. Surg. 18, 85±86.
Fleetwood-Walker, S.M., Mitchelli, R., Hope, P.J., et al., 1985. An
a2receptor mediates the selective inhibition by noradrenaline of nociceptive responses of identi®ed dorsal horn neurons. Brain Res. 334, 243±254.
Gasthuys, F., Terpstra, P., Hende, C.V., DeMoor, A., 1987. Hyperglycaemia and diuresis during sedation with detomidine in the horse. J. Vet. Med. (Series A) 39, 641±648.
Greene, N.M., 1983. Uptake and elimination of local anesthetics during spinal anesthesia. Anesth. Analg. 62, 1013±1024. Grubb, T.L., Riebold, T.W., Huber, M.J., 1992. Comparison of
lidocaine, xylazine and xylazine/lidocaine for caudal epidural analgesia in horses. J. Am. Vet. Med. Assoc. 201, 1187±1190. Grubb, T.L., Reibold, T.W., Huber, M.J., 1993. Evaluation of lidocaine, xylazine and a combination of lidocaine and xylazine for epidural analgesia in Llamas. J. Am. Vet. Med. Assoc. 203, 1441±1444.
Hsu, W.H., Hummel, S.K., 1981. Xylazine induced hyperglycaemia in cattle: a possible involvement of a2-adrenergic receptors
regulating insulin release. Endocrinol. 109, 825±829. Jean, G.St., Skarda, R.T., Muir, W.W., Hoffsis, G.F., 1990. Caudal
epidural analgesia induced by xylazine administration in cows. Am. J. Vet. Res. 51, 1232±1236.
Johnson, R.A., Lopez, M.J., Hendrickson, D.A., Kruse-Elliott, K.T., 1996. Cephalad distribution of three differing volumes of New methylene blue injected into the epidural space in adult goats. Vet. Surg. 25, 448±451.
Kumar, A., Thurmon, J.C., 1978. Physiologic, haemocytologic and biochemical effects of acetylpromazine with and without premedication in goats. Indian Vet. J. 55, 199±201.
Kumar, A., Thurmon, J.C., 1979. Cardiopulmonary, hematocyto-logic and biochemical effects of xylazine in goats. Lab. Anim. Sci. 29, 486±491.
Kuraishi, Y., Hirota, N., Sato, Y., Kaneko, S., Satoh, M., Takagi, H., 1985. Noradrenergic inhibition of the release of substance P from the primary afferents in the rabbit spinal dorsal horn. Brain Res. 359, 177±182.
LeBlanc, P.H., Caron, J.P., Patterson, J.S., Brown, M., Matta, M.A., 1988. Epidural injection of xylazine for perineal analgesia in horses. J. Am. Vet. Med. Assoc. 193, 1405±1408.
Livingston, A., Low, J., Morris, B., 1984. Effects of clonidine and xylazine on body temperature in the rat. Br. J. Pharmacol. 81, 189±195.
Livingston, A., Waterman, A.E., Bouchenafa, O., Kyles, A., 1992. Antinociceptive effects of intrathecal opioids anda2-agonists in
sheep. In: Short, C.E., Poznak, A.V. (Eds.), Animal Pain. Churchill Livingstone, New York, pp. 281±291.
MacDonald, E., Scheinin, H., Scheinin, M., 1988. Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative. Eur. J. Pharmacol. 158, 119±127.
MacDonald, E., Virtanen, R., 1992. Review of the pharmacology of medetomidine and detomidine: two chemically similar a2
-adreconceptor agonists used as veterinary sedatives. In: Short, C.E., Poznak, A.V. (Eds.), Animal Pain. Churchill Livingstone, New York, pp. 181±191.
Makady, F.M., Seleim, S.M., Seleim, M.A., AbdelAll, Th.S., 1991. Comparison of lidocaine and xylazine as epidural analgesics in donkeys. Assiut. Vet. Med. J. 25, 189±195.
Mirakhur, K.K., Sobti, V.K., Nigam, J.M., 1984. Effect of thiopentone anaesthesia on plasma catecholamine and cortisol in buffalo calves (Bubalus bubalis). Indian J. Vet. Surg. 3, 86± 88.
Muir, W.W., Wagner, A.E., Hinchcliff, K., 1992. Cardiorespiratory and MAC-reducing effects of a2-adrenoceptor agonists in
horses. In: Short, C.E., Poznak, A.V. (Eds.), Animal Pain. Churchill Livingstone, New York, pp. 201±212.
Nolan, A., Livingston, A., Waterman, A., 1987. Antinociceptive action of intravenousa2-adrenoceptor agonist in sheep. J. Vet.
Pharmacol. Ther. 110, 202±209.
Ponder, S.W., Clarke, W.G., 1980. Prolonged depression of thermoregulation after xylazine administration to cats. J. Vet. Pharmacol. Ther. 3, 203±207.
Rings, D.M., Muir, W.W., 1982. Cardiopulmonary effects of intramuscular xylazine-ketamine in calves. Can. J. Comp. Med. 46, 386±389.
Skarda, R.T., Muir, W.W., 1992. Physiologic responses after caudal epidural administration of detomidine in horse and xylazine in
cattle. In: Short, C.E., Poznak, A.V. (Eds.), Animal Pain. Churchill Livingstone, New York, pp. 292±302.
Skarda, R.T., Muir, W.W., 1994. Caudal analgesia induced by epidural or subarachnoid administration of detomidine hydro-chloride solution in mares. Am. J. Vet. Res. 55, 670±680. Skarda, R.T., Muir, W.W., 1996. Analgesic, hemodynamic, and
respiratory effects of caudal epidurally administered xylazine hydrochloride solution in mares. Am. J. Vet. Res. 57, 193±200. Snedecor, G.W., Cochran, W.G., 1967. Statistical Methods, 6th
Edition. Oxford and IBH Publishing company, New Delhi. Solimon, M.K., Amrousi, S.E., Khamis, M.Y., 1965. The in¯uence
of tranquilizers and barbiturate anaesthesia on the blood picture and electrolytes of dogs. Vet. Rec. 77, 1256±1261.
Vainio, O., 1983. Detomidine hydrochloride Ð A novel imidazole-type sedative analgesic. In: Ruckebusch, Y., Toutain, P., Koritz, G.D. (Eds.), Veterinary Pharmacology and Toxicology. MTP Press Ltd. Boston, pp. 798±799.
Vesal, N., Cribb, P.H., Frketic, M., 1996. Postoperative analgesic and cardiopulmonary effects in dogs of oxymorphone adminis-tered epidurally and intramuscularly, and medetomidine administered epidurally: a comparative clinical study. Vet. Surg. 25, 361±369.
Virtanen, R., 1986. Pharmacology of detomidine and other a2
-adrenoceptors agonists in the brain. Acta. Vet. Scand. 82, 35± 46.
Virtanen, R., 1989. Pharmacological pro®les of medetomidine and its antagonist atipamezole. Acta. Vet. Scand. Suppl. 85, 29±37. Wagner, A.E., Muir, W.W.III, Hinchcliff, K.W., 1991. Cardiovas-cular effects of xylazine and detomidine in horses. Am. J. Vet. Res. 52, 651±657.
Waterman, A.E., Livingston, A., Bouchenafa, O., 1987. Analgesic effects of intrathecally applied, a2-adrenoceptor agonists in
conscious, unrestrained sheep. Neuropharmacol. 27, 213±216. Yaksh, T.L., 1985. Pharmacology of spinal adrenergic systems
