ISRAEL JOURNAL OF VETERINARY MEDICINE Vol. 57 (2) 2002 A COMPARISON OF EPIDURAL ANAESTHESIA WITH XYLAZINE, BUPIVACAINE AND BUPIVACAINE/XYLAZINE MIXTURE IN WEST AFRICAN DWARF GOATS. Adetunji, A., Ajadi, R. A. and Opia, R E. Department of Veterinary Surgery and Reproduction, University of Ibadan, Ibadan, Nigeria. Abstract Epidurally administered 2% xylazine (0.5mg/kg), bupivacaine (1.7mg/kg), and bupivacaine/xylazine mixture (0.85/0.25mg/kg) were assessed in 5 West African Dwarf (WAD) goats with regard to: time to recucmbency, onset of analgesia, duration of analgesia, duration of recumbency and time to standing. Times to recumbency were found to be 7.0±2.0min for xylazine, 3.8±0.8min for bupivacaine and 6.2±1.3min for bupivacaine/xylazine mixture. Onsets of analgesia with xylazine, bupivacine and bupivacaine/xylazine mixture were respectively 8.4±2.7min, 10.8±3.5 min and 4.8±2.1min. Duration of analgesia was 148.0±23.1min with xylazine, 90.0±2.15 min for bupivacaine and 139.0±57.6min with bupivacaine/xylazine mixture. Duration of recumbency was 117.0±17.2min with xylazine, 174.2±62.3min with bupivacaine, and 138.0±63.6min with bupivacaine/xylazine mixture. Times to standing were 1.2±0.7min with xylazine, 63.2±39.2min with bupivacaine and 45.4±39.0min with bupicacaine/xylazine mixture. Lower cardiac and respiratory rates were produced by epidural xylazine and bupivacaine/xylazine mixture than by bupivacaine alone. It was concluded that whilst prolonged recumbency makes bupivacaine unsuitable for use in the ruminant; bupivacaine/xylazine mixture seems to have no advantage over the use of xylazine alone, considering their similar duration of analgesia and cardio-depressant effects. In fact, its fast recovery would appear to make xylazine a better choice. Introduction Ruminants generally are not considered good subjects for general anaesthesia mainly because of hazards of regurgitation and inhalation of ruminal contents or saliva into the lung if the airway is left unprotected (1,2). Thus, regional anaesthesia produced by the perineural or epidural injections of anaesthetic agents are most frequently employed in these species. The epidural anaesthetics that have been used in small ruminant practice include lignocaine (1,3,4,5) xylazine (5,6) and bupivacaine (5,7). As yet, the ideal epidural anaesthetic for use in goats has not been produced. Whilst the commonly used lignocaine has rapid onset of surgical anaesthesia, it has a short duration of action (1). Used alone, bupivacaine is reputed for slow onset but prolonged duration of action and recovery (2,5). Epidurally administered xylazine in goats reportedly has a slow onset of action but provides prolonged analgesia and rapid recovery (5). In an effort to approach the ideal requirements, the technique of mixing two local anaesthetic agents might be employed to take advantage of the rapid onset of action of one agent and the prolonged duration of action of the other (8). Indeed, mixtures of lignocaine and bupivacaine have been used for several years in human medicine to utilize the beneficial properties of both agents (9,10). In ruminant practice, a lignocaine/xylazine mixture provided rapid onset and prolonged duration of analgesia in llamas (11). To date, however, the use of bupivacaine /xylazine mixture in goats has not been reported. The aim of this study was to compare the effects of the epidurally administered bupivacaine, xylazine and bupivacaine/xylazine mixture in goats with regard to: time to recumbency, onset and duration of analgesia, duration of recumbency, and time to standing. Cardiac rates, respiratory rates and rectal temperatures of the treated goats were also determined at 10-min intervals over a 1-hour period. All trials were carried out in the absence of any manipulative or surgical procedures. Materials and Methods Animals The experimental subjects were 5 mature West Africa Dwarf (WAD) goats, comprising 3 nonpregnant, non-lactating does and 2 intact bucks. Their body weight ranged from 7.8 to 10.1kg (mean±sem 8.6±0.5kg). The animals were housed in a communal goat pen and maintained on Giant star grass (Cynodon alenifuensis), supplemented with cereal-based concentrate and cassava peelings. Drinkable water was made freely available. Just before the commencement of the trials, the goats were judged to be in good health based on clinical findings and haematological evaluation. Experimental Design. Three series of trials were carried out on each goat in a random fashion at 1-week intervals. The first series involved lumbosacral epidural administration of bupivacaine alone; the second series involved similar administration of xylazine alone; while the third series involved similar administration of bupivacaine/xylazine mixture at half their doses when used alone. Experimental procedure For this study, feed and water were not withheld from the goats before undergoing epidural anaesthesia. A pilot study was carried out on two of the goats to determine the effective dose rates to employ of 0.5 percent bupivacaine and 2 percent xylazine. These were found to be 1.7mg/kg and 0.5mg/kg for bupivacaine and xylazine, respectively. The calculated volume of each drug was withdrawn into the syringe and further diluted with 1 ml saline to produce a convenient volume to inject into the epidural space. For each trial, the goat was positioned in sternal recumbency. The lumbosacral region was clipped and prepared for aseptic epidural puncture. With the goat’s hip flexed and its pelvic limbs held along side its abdomen, the lumbosacral site was identified as previously described (1). A sterile 18G by 3.25cm hypodermic needle was inserted into the spinal canal with its bevel directed cranially until it struck the floor of the spinal canal .The needle was then slightly withdrawn into the epidural space. A 5ml syringe containing 1ml of air was attached to the needle to ascertain correct needle placement. The syringe containing appropriate anaesthetic solution was then attached to the needle and the drug was administered slowly over 30 seconds. When recumbent, the treated goat was placed on straw bedding and observed for any druginduced side effects. The onset of analgesia was determined based by the goat’s response to needle pricks over the spinous processes of the vertebrae as well as on the flanks, ventral abdomen and both rear limbs. Measurements Following the lumbosacral epidural injection of the drugs, the goat’s heart rate, respiratory rate and rectal temperature were determined at 10-min intervals over a period of 60min. Heart rate (in beats/min) was determined with the aid of a precordial stethoscope. Respiratory rate (in breaths/min) was counted by visual observation of the thoracoabdominal excursions. Rectal temperature (in degrees Celsius) was measured using a mercury-in-glass clinical thermometer. Calculations The epidural anaesthetic indices calculated for each goat included: time to onset of analgesia, duration of analgesia, time to recumbency, duration of recumbency, and time to standing. These indices were defined as follows: 1. Time to onset of analgesia: time interval (in min) from the epidural injection of drug to loss of response to needle pricks; 2. Duration of analgesia: time interval (in min) from the onset of loss of response to needle pricks to return of the response; 3. Time to recumbency: time interval (in min) from the epidural injection of drug to the goat’s assumption of recumbent posture; 4. Duration of recumbency: time interval (in min) from the goat’s assumption of recumbency to its ability to bear weight on its rear limbs; 5. Time to standing: time interval (in min) from the goat’s assumption of sternal recumbency to its ability to stand and walk. Data Analysis Data are expressed as means (± sem) of 5 goats. The measured physiological variables were compared using ANOVA for repeated measures. Where significant differences were indicated by ANOVA, least significant difference test was employed as post-test. The epidural anaesthetic indices were compared using (students) “t” test for paired data; a P value of 0.05 was accepted as being significant in all comparisons. Results Observations Both solutions of 0.5 percent bupivacaine and 2 percent xylazine appeared to be miscible in the syringe as no colour change or precipitation resulted from mixing. The lumbosacral epidural administration of xylazine or bupivacaine/xylazine mixture was associated with such side-effects as sedation, salivation, apnoea, ruminal tympany, phonation, grunting and urination (Table I). Similarly administered bupivacaine was only associated with phonation and post-recumbent ataxia (Table I). The xylazine-induced sedation made additional physical restraint of the treated goat unnecessary. The observed ruminal tympany was of a mild degree that was resolved only by needle paracentesis of the rumen. Salivation was managed mainly by postural drainage unto the floor. None of the goats showed inappetence when offered grass immediately on standing up. Table I: Side effects of Lumbosacral epidural bupivacaine (1.7mg/kg) xylazine (0.5mg/kg) and bupivacaine/xylazine mixture (0.85/025mg/kg) in 5 WAD goats. Bupivacain Group Xylazine Group Bupivacaine/ Xylazine group Sedation 0 +5 +4 Salivation 0 +5 +4 Apnoea 0 +3 +2 Bloat 0 +4 +2 Phonation +2 +2 +3 Grunting 0 +2 +1 Urination 0 +5 +4 Ataxia d +4 0 +1 0 Not observed + Observed d in the post-recumbent period Table II: Heart rates of goats under epidural anaesthersia with bupivacaine (1.7mg/kg) xylazine(0.5mg/kg) and bupivacaine/xylazine misture (0.85/025mgkg) Time (min) from onset of drug effect Bupivacain Group Xylazine Group Bupivacaine/ Xylazine Group 0 131.6±13.6 710±6.0* 80.6±10.0* 10 125.0±7.9 69.0±2.4* 80.2±8.5* 20 127.4±7.4 67.8±3.8* 77.4±7.9* 30 117.2±11.4 69.6±5.0* 81.2±8.5* 40 130.0±5.1 68.2±5.7* 76.8±8.5* 50 136.8±10.7 64.8±6.5* 80.0±8.8* 60 124.8±8.1 68.4±7.2* 79.6±8.8* Data are expressed as mean± sem of 5 goats *P<0.05 vs. bupivacaine group Table III: Respiratory rates of goats under epidural anaesthesia with bupivacaine (1.7mg/kg) xylazine(0.5mg/kg) and bupivacaine/xylazine mixture (0.85/0.25 mg/kg). Time Interval (min) Bupivacain Group Xylazine Group Bupivacaine / Xylazine Group 0d 45.6±6.6 17.8±2.7* 28.6±8.5* 10 39.2±4.0 14.4±2.7* 17.0±1.5* 20 36.6±5.9 17.6±1.9* 14,6±2.2* 30 31.2±3.8 9.4±8.1* 27.0±4.1* 40 28.0±3.7 15.2±1.6* 22.4±6.3* 50 40.8±9.3 17.4±2.0* 19.0±5.3* 60 49.8±18.0 18.0±2.3* 22.0±6.2* Data are expressed as mean ± sem of 5 goats d: data obtained at the onset of drug effect * P<0.05 vs. bupivacaine group Measured Variables The epidurally administered xylazine or bupivacaine/xylazine mixture was associated with significantly lowered mean heart and respiratory rates than with bupivacaine alone. Both of these variables decreased to about half the corresponding values in the bupivacaine group (Tables II and III). Alterations in mean rectal temperatures in all the three treatment groups were not significantly different (Table IV). Table IV: Rectal temperatures of goats under epidural anaesthesia with bupivacaine (1.7mg/kg) xylazine (0.5mg/kg) and bupivacaine/xylazine mixture (0.85/0.25mg/kg) Time Interval (min) Bupivacain Group Xylazine Group Bupivacaine / Xylazine Group 0d 39.3±0.4 38.3±0.5 39.6±0.4* 10 39.2±0.4 38.6±0.4 39.5±0.5 20 39.1±0.3 38.3±0.4 39.2±0.5 30 40.3±0.4 38.1±0.5 38.9±0.5 40 39.1±0.3 37.9±0.4 38.7±0.5 50 39.8±0.4 38.0±0.4 38.3±0.5 60 39.2±0.4 37.9±0.6 38.2±0.5 Data are expressed as mean ± sem of 5 goats d: data obtained at the onset of drug effect * P<0.05vs bupivacaine group Epidural Anaesthetic Indices The calculated epidural anaesthetic indices are shown in Table V. Time to recumbency was significantly shorter with bupivacaine (3.0± 0.8min) than with xylazine (7.0±2.0 min), or bupivacaine /xylazine mixture (6.2±1.3min). Onset of analgesia was significantly shorter with bupivacaine/xylazine mixture (4.8±3.5min) than with bupivacaine (10.8±3.5min) or xylazine (8.4±2.7min). Duration of analgesia was significantly longer with xylazine (148.0±23.1min) or bupivacaine/xylazine mixture (139.0±57.6min) than with bupivacaine (90.0 ±21.5min). Duration of recumbncy was significantly longer with bupivacaine (174.2±62.3min) than with xylazine (117.0±17.2min) or bupivacaine/xylazine mixture (138.0±63.6 min). Time to standing was shortest with xylazine (1.2± 0.7min) than with bupivacaine (63.2±39.2min) and bupivacaine/xylazine mixture (45.4±390min). Table V: Epidural anaesthetic indices of bupivacaine (1.7mg/kg) xylazine (0.5mg/kg) and bupivacaine mixture (0.85/0.25mg/kg) in 5 WAD goats. Time (min.) Variable Bupivacain Group Xylazine Group Bupivacaine/Xylazine Group Time to recumbency D 38.±0.8 7.0±2.0* 6.2±1.3 Onset of analgesia E 10.8±3.5 8.4±2.7 4.8±2.1* Duration of analgesia F 90.0±21.5 148.0±23.1* 139.0±57.6 Duration of recumbency G 174.2±62.3 117.0±17.2 138.0±63.6 Time to standing H 63.2±39.2 1.2±0.7* 45.4±39.0 Data are expressed as mean ± sem of 5 goats D: interval between epidural drug injection and inability to stand. E: interval between epidural drug injection and loss of pain response F: interval between loss and return of pain response G: interval between onset of recumbency and standing. H: interval between sternal and standing postures * P<0.05vs. bupivacaine. Discussion The results of this trial show that epidurally administered bupivacainel/xylazine mixture in goats had a shorter onset of analgesia than either component, a similar duration of analgesia to xylazine alone, a shorter duration of recumbency than with bupivacaine alone, but a longer time to standing than with xylazine alone. In addition, the drug mixture produced lower heart and respiratory rates than bupivacaine alone. The spread of anaesthetic solutions within the epidural space is known to be influenced by a variety of factors, including age, obesity, pregnancy and body posture (12,13); Therefore, aged, obese and pregnant goats were not included in this study in order to obtain valid data for comparison. In addition, the goats were restrained in sternal recumbency for a while after epidural injection thereby keeping the spine horizontal to obtain a bilateral block. Although sedation has been recommended for routine use in animals to facilitate epidural administration of anaesthetic agents (13), the use of a sedative drug was deliberately omitted in this study to avoid its possible confounding effects on the physiological variables being measured. The finding that solutions of bupivacaine (an amide type local anaesthetic) and xylazine (an a2adrenergic agonist) appeared completely miscible in the syringe is interesting. This suggests that the pH values of both agents do not differ widely. However, this supposition could not be supported as the pHs of the solutions were not determined in this study. Nonetheless, it is reasonable to expect other drugs from both pharmacological classes to be similarly miscible. A number of side effects were associated with the epidurally administered bupivacaine/xylazine mixture and xylazine alone in this study (Table1). It is certain that most of these side effects were produced by the xylazine component of the mixture since they were not observed with epidural bupivacaine alone. Furthermore, similar side effects have been associated with systemically administered xylazine in ruminants (2). Whereas the induced sedation made additional manual restraint of the treated goats needless and grunting and phonation are clinically insignificant, salivation, bloat and urination have profound clinical implications. Therefore epidural xylazine and bupivacaine/xylazine mixture would appear to be good only in selected patients. Duration of analgesia of 90.0±21.5min produced by epidural bupivacaine in this study (Table V) is not in accord with the several hours reported by Trim (7) who employed 0.75% solution at a dose rate of 1.9mg/kg and with 145.0±7.2min reported by Mohammed (5) using 0.5% solution at a dose of 1.5mg/kg. These discrepancies may relate to differences in the concentrations and dosages of the drug employed in this and previous similar studies. Furthermore, 0.5% bupivacaine might have produced partial motor blockade as in humans (14) causing the treated goats to withdraw their pelvic limbs when stimulated. This phenomenon might have been confused with the return of pain responses, thereby leading to gross underestimation of the duration of analgesia. Duration of analgesia of 148.0±23.1min produced by epidural xylazine in this study compares well with 151.7±6.6min reported by Mohammed (5) in a similar study using 0.4mg/kg xylazine in WAD goats. Duration time of analgesia of 139.0±57.6 min produced by epidural bupivacaine/xylazine mixture (Table V) clearly represent a synergistic effect of both agents. In this study, time to standing of 63.2±39.2min compares well with 58±148min reported by Mohammed (5) in a similar study using 0.5% bupivacaine in WAD goats. Such prolonged recovery is certainly undesirable. The time period during which a ruminant is recumbent should ideally be minimal, to enable the animal to become ambulatory before the practioner leaves the premises. This requirement would appear to be best met by epidural xylazine with a time to standing of 12±0.7min (Table V). In this study, epidurally administered xylazine, and bupivacaine/xylazine mixture produced profound cardioresporatory depression (Tables II&III). Again, this effect is attributable to the xylazine component since epidural bupivacaine alone maintains cardial and respiratory functions. This finding implies that epidural xylazine and bupivacaine/xylazine mixture could be used only in selected patients. In conclusion, epidural bupivacaine at the dose rate used in this study had the shortest duration of analgesia but the longest duration of recumbency and therefore unsuitable for use in the ruminant. In view of the similar duration of analgesia and cardiorespiratory depression produced by epidural xylazine and bupivacaine/xylazine mixture, the latter appears to have no advantage over the former. Indeed, the brief time to standing associated with epidural xylazine would appear to make it a better choice for epidural administration in the goat. References 1. Hall L.W.and Clarke K.W.: Veterinary Anaesthesia 9th ed., Balliere Tindall, London 1991. 2. Trim C.M.: Sedation and general anaesthesia in ruminants Calif. Vet.4: 29-36, 1981. 3. Gray, P.R., M.C Donell W.W.: Anaesthesia in goats and sheep, 1 Local analgesia compend Cont. Educ. Pract. Vet 8: 533-539, 1986. 4. Nelson, D.R., Benson, G. J. and Thurmon, J.C.: Spinal analgesia and sedation of goat with lignocaine and xylazine. Vet. Rec. 105:278-280, 1979. 5. Mohammed, A.U.: Comparison of lignocaine, bupivacaine and xylazine for epidural anaesthesia in West African Dwarf goats. MVSC thesis, University of Ibadan. p. 68, 1997. 6. Scott, P.R.and Gassert, M.E.: Evaluation of extradural xylazine injection for caesarian operation in ovine dystocia cases. The Vet. Journal 154:63-67,1997. 7. Trim, C.M.: Epidural analgesia with 0.75% bupivacaine for laparotomy in goats. J. Am Vet. Med. Assoc. 194:1292-1296, 1989. 8. Moore, D.C., Bridenbaugh, L.D., Bridenbaugh, Z., Thomson, G.E. and Tucker, G.T.: Does compounding of Local anesthetic agent increase toxicity in human Aneasth. Ann. (Clere) 51:579585, 1972. 9. Magee, D.A., Sweet, P.T. and Holland, A.J.C.: Epidural anaesthesia with mixture of bupivacaine and lidocaine. Can. Anaesth. Soc. J. 30: 174-178,1983. 10. Seow, L.T., Lips, P.S., Cousins, M. J. and Mather, L.E.: Lidocaine and bupivacaine mixtures for epidural blockade.Anaesthesiology 56:177-183, 1982. 11. Grubb, T.L., Riebold, T.W. and Haber. M.S.: Evaluation of lidocaine, xylazine and a combination of lidocaine and xylazine for epidural analgesia in Ilamas. J. Vet. Med. Assoc. 203:1411-1414, 1993. 12. Bromage, P.R.: Spread of analgesic solutions in the epidural space and their site of action. Br. J. Anaesth. 34:361-365, 1962. 13. Klide, A.M. and Soma, L.R.: Epidural analgesia in the dog and cat J.Am. Vet. Med. Assoc.153: 165-172, 1968. 14. Scott, D.B., Mcclure, J.T., Grasi, R.M., Seok, Covino BG.: Effects of concentrations of local anaesthetic drugs on epidural block Br.J.Anaesth. 52:1033-1037, 1980.