VETERINARSKI ARHIV 69 (6), 327-333, 1999

ISSN 1331-8055 Published in Croatia




Epidural administration of xylazine-lidocaine mixture in sheep - analgesic and cardiopulmonary effects

Bogdan Aminkov*

Department of Surgery and Radiology, Faculty of Veterinary Medicine, Stara Zagora, Bulgaria




* Contact address:
Prof. Dr. Bogdan Aminkov,
Department of Surgery and Radiology, Faculty of Veterinary Medicine, Thracian University, Student's Campus, 6000 Stara Zagora, Bulgaria,
Phone: 359 42 601 473


AMINKOV, B.: Epidural administration of xylazine-lidocaine mixture in sheep - analgesic and cardiopulmonary effects. Vet. arhiv 69, 327-333, 1999.

ABSTRACT

The present study was conducted to investigate the effect of epidural lidocaine and xylazine on sedation, analgesia and respiratory and cardiovascular functions in sheep. A mixture of 0.2 mg/kg xylazine (2% Rompun, Bayer) and 10 ml 2% lidocaine was epidurally introduced in 7 clinically healthy sheep. An auricularis artery was catheterised for measurement of mean arterial blood pressure (MABP) and for collection of blood samples. Analgesia was determined by lack of response to needle pinprick stimulation. Epidurally administered mixture induced bilateral analgesia extending from hind limbs to vertebrae Th7-Th8. Time to onset of analgesia was at 3-5 minutes of the administration of mixture and lasted from 180 to 240 minutes. Significant reduction in MABP was established at minute 60 (P<0.05) and in haemoglobin and oxygen content at intervals from minutes 30 to 60 (P<0.05). In conclusion, the epidurally administered mixture xylazine/lidocaine was shown to induce safely prolonged analgesia with minimal circulatory and respiratory disturbances in sheep.

Key words: epidural analgesia, xylazine, lidocaine, sheep



Introduction

The most frequently employed local anaesthetic agent for epidural analgesia is lidocaine, which provides analgesia for 60 to 90 minutes and which is often insufficient to complete procedures (SKARDA, 1982; LEBLANC, 1990).

Xylazine is used mainly intravenously or intramusculary. These routes of administration frequently cause untoward effects, such as bradycardia, hypotension, hypoxaemia (DOHERTY, 1986; AZIZ and CARLYLE, 1997) and tachypnea. These side effects are only minimally exhibited after epidural administration of xylazine in sheep (AMINKOV and PASKALEV, 1998).

Recently, to achieve analgesia with a longer duration, some investigators have used a combination of a local anaesthetic agent and an alpha-adrenergic agonist in human medicine (NEIMI, 1994; KLIMSCHA et al., 1995), dogs (BEDDER et al., 1986), horses (GRUBB et al., 1992) and llamas (GRUBB et al., 1993).

The purpose of this study was to investigate the analgesia and cardiopulmonary effects after epidural administration of xylazine/lidocaine mixture in sheep.

Materials and methods

Seven clinical healthy sheep, with masses of 48±3 kg, were used. Feed was withheld for 24 h and water-8 h prior to the experiment.

For the epidural anaesthesia the animals were in right lateral recumbence on a table with hind limbs extended forward. Following subcutaneous infiltration with 3 ml 2% lidocaine (Lidocaine, Pharma- chim), a 16-gauge 8 cm-long Tuohy needle (Braun Melsungen AG) was inserted into the epidural space at the interspace between the last lumbal and first sacral vertebrae. The site for lumbosacral injection was located as follows: the anterior border of the ilium on each side was located by palpation. An imaginary line, joining the spinous process of the last lumbal vertebra was drawn and the needle was introduced immediately behind this. The epidural space was identified by loss of resistance to injection of 2 ml of air after piercing the ligamentum flavum (HALL and CLARKE, 1983). A catheter with 3 lateral eyes, 0.6×1.05×100 mm, was threaded forward through the needle for 5 cm beyond the needle bevel; the needle was removed with the catheter in place.

A mixture of 2% solution of xylazine (Rompun, Bayer) (0.2 mg/kg body mass) plus 10 ml of 2% lidocaine hydrochloride was injected slowly into the epidural space. Immediately after the solution was injected, the sheep were placed in dorsal recumbency for 5 min.

A 22-gauge 5 cm catheter was placed into the auricular artery for determination of mean arterial blood pressure (MABP, mmHg), as well as for collecting arterial blood samples. The pressure waveform was obtained using calibrated strain-gauge transducers. The point of the shoulder was considered as the zero point. Mean blood pressure was obtained by electric integration of the signal from blood pressure transducer.

Heart rate (HR, beats/min) was determined through counting the pulse waves on the oscillograph (Hellige GmBH) for one minute. A snug fitting face was positioned over the mouth and nose of each sheep. Exhaled gas volume was measured using a respirometer (Atemvolumer BZ03, VEB Medizintechnik). Body temperature was measured using an electronic rectal thermometer.

Blood parameters, heart rate (HR), respiratory rate (RR), tidal volume (TV) and rectal temperature were recorded before (baseline, 0) and at 10, 30, 45, and 60 min after epidural administration of the solution.

The following acid-base and blood gas parameters were estimated on an automated analyser (ABL-3, Radiometer): blood pH; partial O2 and CO2 pressures in mmHg; blood bicarbonates (HCO3 in mmol/l), oxygen content (O2CT), oxygen saturation (SAT, %), the base excess (ABE, mmol/l), haemoglobin (Hb, g/dl). Blood samples were immediately ana- lysed. All blood gas measurements were corrected to body temperature.

Analgesia was assessed by response to superficial and deep muscular pinpricks over the whole body and was defined as lack of movement or no attempt to kick or turn the head toward the site of pinprick. Sedation was assessed by observation of dropping of the upper eyelids. Recovery from anaesthesia was in a quiet environment (room) and was determined as the moment that the animals were able to stand spontaneously and to maintain that position.

The results were expressed as mean ±SEM and submitted to a statistical analysis of variance (ANOVA) with one within factor (time). Post-hoc comparisons of individual group means were carried out by the least significance difference test.

Results

The preliminary investigation established that epidural analgesia with 0.2 mg/kg xylazine caused analgesia with a duration of 25-30 min, without ataxia and hind limb weakness. Administration of the mixture caused a hind limb weakness for 2-3 min, after which the sheep lay down. The onset of analgesia was at min 35 and the duration of action 180-270 min.

The sheep stood independently until hour 5.20.

Cardiopulmonary changes after epidural administration of the lidocaine-xylazine mixture are shown in Table 1. MABP was decreased throughout the whole period of the study, and at min 60 it reached 96±8 mmHg compared to the initial rate of 105±7 mmHg (P<0.05). Haemaglobin and O2CT levels decreased gradually during the experimental period. Significant changes were observed at minutes 30, 45, 60 (P<0.05; P<0.001). This was valid for ABE at min 45 (P<0.05) and min 60 (P<0.001) too.

Table 1. Cardiopulmonary and acid-base effects of epidural
administration of xylazine+lidocaine in sheep (N=7; mean±SEM)

Variable

Baseline

Minutes after administration

10

30

45

60

Mean arterial blood pressure

105±7

102±7

99±4

97±6

17±4

Heart rate (1/min)

85±3

76±3

69±2

71±3

68±4

Respiratory rate (1/min)

25±2

23±2

19±2

18±1

19±1

Tidal volume

343±23

311±22

247±29

247±24

257±32

Haemoglobin (g/dl)

10.7±0.2

9.3±0.3

8.9*±0.2

8.4***±0.2

8.6**±0.2

Partial O2

100.3±3.7

92.5±3.2

91.2±1.9

93.3±2.8

93.1±3.5

Oxgen saturation (%)

96.8±0.4

96.4±0.3

96.3±0.2

96.6±0.3

96.9±0.4

Oxen content (vol %)

14.6±0.3

12.6±0.4

12.0*±3.2

11.5**±0.2

11.8**±0.3

Blood pH

7.445±0.012

7.458±0.009

7.458±0.009

7.467±0.008

7.484±0.006

Partial CO2

37.3±0.7

38.4±0.6

40.5±0.6

40.8±0.6

41.1±0.3

Blood bicarbonates

24.9±0.8

26.1±0.7

28.2±0.6

29.1±0.6

29.9±0.6

Base excess

1.9±0.5

3.3±0.6

4.6±0.5

5.5*±0.5

6.7***±0.4

Body temperatures (°C)

39.1±0.1

38.9±0.2

38.5±1.6

38.4±0.2

38.2±0.2

*P<0.05; **P<0.01; ***P<0.001 vs baseline



Discussion

The results of the present study evidenced clearly that the epidurally co-administration of xylazine and lidocaine improved the duration of analgesia. Epidurally administered lidocaine in sheep resulted in analgesia within 5-15 min, which lasted from 60 to 90 min. Hind limb paralysis lasted for nearly 3 hours after the epidural injection of lidocaine (HAL and CLARKE, 1983). Lidocaine induced analgesia by inhibiting propagation and conduction of nerve impulses through blockade of sodium channels in the cell with subsequent prevention of depolarisation (COVINO, 1990), while xylazine induces analgesia through local anaesthesia action (AZIZ and MARTIN, 1978) and an alpha-2-adrenergic mechanism (HOWE et al., 1983). In this study the lidocaine+xylazine mixture produced anaesthesia with a faster onset and prolonged duration. The exact mechanism by which an alpha-2-agonist induced prolongation of analgesia is not known. The possible mechanism of an alpha-2-agonist induced prolongation of analgesia is through adrenoceptor mediated vasoconstrictors (KIOWSKI et al., 1983) and inhibition of local anaesthetic vasodilatory effects (MENSINK et al., 1987).

The prolongation of sensory blockade could also be explained by a synergism between the antinociceptive effects of xylazine and the neural blocking action of lidocaine (BEDDER et al., 1986).

The main disadvantage of this method was profound sedation and prolonged motor blockade. The same effects were observed after epidural administration of xylazine in cattle (CARON and LEBLANC, 1989). This was most probably due to the specific sensitivity to alpha-2-agonists.

Changes in arterial blood pressure were dependent on the site of administration and the dose of alpha-2-agonists. Alpha-2-agonists decrease blood pressure more when they are injected at the thoracic level, close to the preganglionic sympathetic neurones, than when being injected at the lumbal or cervical level in sheep (EISENACH and TONG, 1991).

The alpha-2-agonists decrease blood pressure at low doses presumably due to action of brain stem sites (GUYNET and CABOT, 1987) and increased blood pressure at higher doses due to direct constricting effects on the peripheral vascular site of haemodynamic (LANGER et al., 1985). Epidural administration of 0.2 mg/kg xylazine diluted with 10 ml in sheep does not cause significant changes in arterial pressure (AMINKOV and PASCALEV, 1998). In this work the observed arterial blood pressure changes were due to sympathetic action of lidocaine.

The decrease in haemoglobin concentrations in this study may be explained by pooling of circulating erythrocytes in the spleen or their reservoirs secondary to decreased sympathetic activity. The quantitative decrease in haemoglobin concentration may explain the calculated decrease in O2CT.

Epidural administration of 0.4 mg/kg xylazine in rams caused metabolic acidosis (AMINKOV and HUBENOV, 1995). Similar changes were also observed by others after epidural injection of xylazine in cattle (SKARDA, 1990). In this study, a significant increase was established only for base excess.

In conclusion, the addition of xylazine to lidocaine results in long lasting analgesia with moderate cardiopulmonary changes.

References

AMINKOV, B. Y., H. D. HUBENOV (1995): The effect of xylazine epidural anaesthesia on blood gas and acid-base parameters in rams. Br. Vet. J. 151, 579-585.

AMINKOV, B. Y., M. D. PASCALEV (1998): Cardiovascular and respiratory effects of epidural vs intravenous xylazine in sheep. Revue Med. Vet. 149, 1, 69-74.

AZIZ, M. A., S. S. CARLYLE (1997): Cardiovascular and respiratory effects of xylazine in sheep. J. Vet. Med. 25, 173-180.

AZIZ, M. A., R. J. MARTIN (1978): Alpha agonist and local anaesthetic properties of xylazine. Zentralbl. Veterinär Med. 25, 181-188.

BEDDER, M. D., R. KOZODY, R. J. PALAHNUIK, M. O. CUMMING, W. R. RUCCI (1986): Clonidine prolongs canine tetracaine spinal anaesthesia. Can. Anaesth. Soc. J. 33, 591-596.

CARON, J. P., P. H. LEBLANC (1989): Caudal epidural analgesia in cattle using xylazine. Can. J. Vet. Res. 53, 486-489.

COVINO, B. G. (1990): The pharmacologic basis for choosing a local anesthetic. In: Proceedings Ann. Meet. An. Soc. Anesth. 131, 1-6.

DOHERTY, T. J., P. J. PASCAL, W. N. MCDONELL, G. MONTEITH (1986): Cardiopulmonary effects of xylazine and yohimbine in laterally recumbent sheep. Can. J. Vet. Res. 50, 517-521.

EISENACH, J. C., Ch. TONG (1991): Site of hemodynamic effects of intrathecal alpha-2-adrenergic agonists. Anesthesiology 74, 766-771.

GRUBB, T. L., T. W. RIEBOLD, M. J. HUBER (1993): Evaluation of lidocaine, xylazine and a combination of lidocaine and xylazine for epidural anaesthesia in llamas. JAVMA 203, 1441-1444.

GRUBB, T. L., T. W. RIEBOLD, M. J. HUBER (1992): Comparison of lidocaine, xylazine and lidocaine/xylazine for caudal epidural analgesia in horses. JAVMA 201, 1187-1190.

GUYNET, P. T., J. B. CABOT (1987): Inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-2-adrenergic receptor. J. Neurosci. 1, 908-917.

HALL, L. W., K. W. CLARKE (1983): Veterinary Anaesthesia. 8th ed. Baillière-Tindall. London.

HOWE, J. R., S. Y. WANG, T. L. YAKSH (1983): Selective antagonism of the antinociceptive effect of intrathecally applied alpha-2-adrenergic agonists by intrathecal prazocin and intrathecal yohimbine. J. Pharm. Exper. Ther. 224, 552-558.

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KLIMSCHA, W., A. CHIARI, P. KRAFFT, O. PLATTNER, R. TASLIMI, N. MAYER, C. WEINSTABLE, B. SCHNEIDER, M. ZIMPFER (1995): Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks. Anesth. Anal. 80, 322-327.

LANGER, S. Z., N. DUVAL, R. MASSINGHAM (1985): Pharmacologic and therapeutic significance of alpha-adrenoreceptor subtypes. Cardiovasc. Pharmacol. 7 (suppl. 8), 1-8.

LEBLANC, P. H. (1990): Regional anesthesia. Vet. Clin. North Am. Equine Prac. 6, 693-704.

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Received: 25 August 1999
Accepted: 17 December 1999



AMINKOV, B.: Analgeticko i kardiopulmonalno djelovanje epiduralne primjene mjesavine ksilazina i lidokaina u ovce. Vet. arhiv 69, 327-333, 1999.

SAZETAK

Ovo je istrazivanje provedeno sa svrhom da se utvrdi djelovanje epiduralne primjene lidokaina i ksilazina na sedaciju i analgeziju, te djelovanje na disne i kardiovaskularne funkcije u ovce. Mjesavina 0,2 mg/kg ksilazina (2%-tni Rompun, Bayer) i 10 ml 2%-tnog lidokaina primijenjena je epiduralno u sedam klinicki zdravih ovaca. Kateter je uveden u arteriju uske, za mjerenje srednjeg arterijskog krvnog tlaka i za uzimanje uzoraka krvi. Analgezija je bila utvrdena kada nije bilo reakcije zivotinje na ubadanje iglom. Epiduralno primijenjena mjesavina izazvala je obostranu analgeziju koja se protezala od straznjih nogu do 7. ili 8. grudnog kraljeska. Pocetak analgezije uocen je 3-5 minuta nakon davanja mjesavine, a analgezija je trajala od 180 do 240 minuta. Znacajni pad srednjega arterijskog krvnog tlaka utvrden je u 60. minuti (P<0,05), a hemoglobina i sadrzaja kisika izmedu 30. i 60. minute (P<=0,05). Moze se zakljuciti da epiduralna primjena mjesavine ksilazina i lidokaina izaziva pouzdano produzenu analgeziju s neznatnim cirkulatornim i respiratornim nuspojavama u ovce.

Kljucne rijeci: epiduralna analgezija, ksilazin, lidokain, ovca


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