The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole

OBJECTIVE: To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). STUDY DESIGN: Prospective, randomized, cross-over. ANIMALS: Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. RESULTS: Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. CONCLUSIONS: At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. CLINICAL RELEVANCE: Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.     

Cardiovascular and haemodynamic effects of intramuscular doses of xylazine in conscious sheep

OBJECTIVE: To determine if a commonly used analgesic dose of xylazine has detrimental cardiovascular or haemodynamic effects in sheep. DESIGN: A physiological study following intramuscular administration of xylazine. PROCEDURE: Xylazine (50 micrograms/kg) was injected intramuscularly into six healthy Merino ewes. For 60 min heart rate, mean arterial blood pressure and cardiac output were recorded; arterial blood samples for the measurement of blood gas tensions were also collected. RESULTS: There were no significant changes in heart rate, mean arterial blood pressure, cardiac output or arterial carbon dioxide tension. A slight degree of arterial hypoxaemia was noted with a 10% reduction in arterial oxygen tension values at 30 min. CONCLUSION: The minimal changes to cardiovascular and respiratory values in this study verify the safety of previously suggested analgesic dosing regimens for sheep. Previously reported hypoxaemic effects in sheep as a result of intravenous xylazine administration appear to be reduced as a result of intramuscular administration.     

The extradural pressure profile in goats following extradural injection

ObjectiveTo measure the extradural pressures in goats before and after extradural injection, and to investigate the occurrence of extradural pressure waves.Study designProspective experimental trial.AnimalsNine healthy adult goats weighing 59.4 ± 6.4 kg, scheduled for stifle arthroscopy.MethodsThe goats were pre–medicated with midazolam and anaesthesia was induced with propofol and maintained with sevoflurane. The goats were placed in lateral recumbency and extradural puncture was performed via the lumbosacral space. Correct placement of the needle was assessed by lack of resistance to the injection of saline. The needle was connected to an electronic pressure transducer to record extradural pressure. Measurements were taken before and after extradural injection of methadone (0.1 mg kg^?1, diluted to a total volume of 0.2 mL kg^?1) and 10 minutes later. Contrast medium was injected and correct extradural needle placement confirmed by radiography.ResultsLack of resistance to injection of saline occurred in all goats, but there were no pressure waves observed before injection in any animal. Radiography indicated incorrect needle placement in four animals and one had pressure waves synchronous with the arterial pulse after methadone injection. Correct needle placement was confirmed in the remaining five animals which exhibited pressure waves after extradural methadone injection. In the five goats with successful needle placement the baseline extradural pressure ranged from 0.4 to 2.5 kPa (3–19 mmHg), increasing to 4.4–39.9 kPa (33–300 mmHg) after injection. Ten minutes after injection, extradural pressure remained elevated and ranged from 2.5 to 17.3 kPa (19–130 mmHg).Conclusions and clinical relevanceExtradural pressure waves were not useful to confirm correct extradural needle placement in laterally recumbent goats. The presence of such waves after injection of 0.2 mL kg^?1 may be indicative of correct placement but even here we saw one of nine animals with extradural pressure waves where we failed to confirm correct needle placement. Extradural pressure increases after extradural injection.     

Concentrations of vatinoxan and xylazine in plasma,cerebrospinal fluid and brain tissue following intravenous administration in sheep

ObjectivesTo investigate the extent of vatinoxan distribution into sheep brain, and whether vatinoxan influences brain concentrations of xylazine; and to examine the utility of cerebrospinal fluid (CSF) as a surrogate of brain tissue concentrations for vatinoxan and xylazine.Study designRandomised, blinded, experimental study.AnimalsA total of 14 adult female sheep.MethodsSheep were randomly allocated into two equal groups and premedicated with either intravenous (IV) vatinoxan (750 μg kg^–1, VX) or saline (SX) administered 10 minutes before IV xylazine (500 μg kg^–1). Sedation was subjectively assessed at selected intervals before and after treatments. At 10 minutes after xylazine administration, a venous blood sample was collected and the sheep were immediately euthanised with IV pentobarbital (100 mg kg^–1). Plasma, CSF and brain tissues were harvested, and concentrations of vatinoxan and xylazine were quantified using liquid chromatography–tandem mass spectrometry. Drug ratios were then calculated and the data were analysed as appropriate.ResultsThe brain-to-plasma and CSF-to-plasma ratios of vatinoxan were 0.06 ± 0.013 and 0.05 ± 0.01 (mean ± standard deviation), respectively. Xylazine brain concentrations were not significantly different (835 ± 262 versus 1029 ± 297 ng g^–1 in groups VX and SX, respectively) and were approximately 15-fold higher than those in plasma. The CSF-to-brain ratio of vatinoxan was 0.8 ± 0.2, whereas xylazine concentrations in the brain were approximately 17-fold greater than those in CSF, with and without vatinoxan.Conclusions and clinical relevanceVatinoxan did not significantly affect sedation with xylazine or the concentrations of xylazine in the brain. CSF is not a good predictor of xylazine concentrations in the brain, whereas vatinoxan concentrations were concordant between the brain and CSF, using the dosages in this study.     

Effect of bupivacaine on epidural analgesia produced by xylazine or medetomidine in buffaloes (Bubalus bubalis)

ObjectiveTo evaluate and compare the effect of epidural bupivacaine on analgesia produced by epidural xylazine or medetomidine in buffaloes.Study designProspective, blinded study.AnimalsTen male buffalo calves (6-8 months of age; body weight 70-90 kg) were used on two occasions to conduct a total of 20 investigations.MethodsCaudal extradural analgesia was produced in four buffalo calves each by the injection of either xylazine (0.05 mg kg^?1), medetomidine (15 μg kg^?1) or 0.5% bupivacaine (0.125 mg kg^?1), or combinations of xylazine and bupivacaine (0.05 and 0.125 mg kg^?1), or medetomidine and bupivacaine (15 μg kg^?1 and 0.125 mg kg^?1) at the first intercoccygeal extradural space. Analgesia was tested using deep pinprick stimuli.ResultsExtradural administration of xylazine or medetomidine resulted in complete analgesia of the tail, perineum, inguinal region and the upper parts of the hind limbs, which was faster in onset and longer in duration in the medetomidine group than in the xylazine group. Addition of bupivacaine increased the intensity of the analgesia produced by xylazine, but not that produced by medetomidine. All the drugs caused mild to moderate ataxia, but signs of sedation were apparent only in animals which received xylazine or medetomidine. The extradural injections of all the drugs caused significant decrease in heart rate (p = 0.024), respiratory rate (p = 0.026) and rectal temperature (p = 0.036) from the respective baseline values, but the differences between the groups were not significant.ConclusionsMedetomidine produced a longer duration of analgesia than that produced by xylazine. Bupivacaine prolonged the analgesia produced by xylazine, but the analgesia produced by the combination of medetomidine and bupivacaine was not superior to that produced by medetomidine alone.Clinical relevanceBupivacaine may be used to prolong the extradural analgesia produced by xylazine, but not that produced by medetomidine in buffaloes.     

Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane‐anaesthetized sheep

ObjectiveTo determine the anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in sheep anaesthetized with isoflurane and undergoing orthopaedic surgery.Study designProspective, randomised, ‘blinded’ controlled study.AnimalsTwenty healthy sheep (weight mean 41.1 ± SD 4.5 kg).MethodsSheep were sedated with intravenous (IV) dexmedetomidine (4 μg kg⁻¹) and morphine (0.2 mg kg⁻¹). Anaesthesia was induced with propofol (1 mg kg⁻¹ minute⁻¹ to effect IV) and maintained with isoflurane in oxygen and a continuous rate infusion (CRI) of fentanyl 10 μg kg⁻¹ hour⁻¹ (group F) or saline (group P) for 100 minutes. The anaesthetic induction dose of propofol, isoflurane expiratory fraction (Fe’iso) required for maintenance and cardiorespiratory measurements were recorded and blood gases analyzed at predetermined intervals. The quality of recovery was assessed. Results were compared between groups using t-tests or Mann–Whitney as relevant.ResultsThe propofol induction dose was 4.7 ± 2.4 mg kg⁻¹. Fe’iso was significantly lower (by 22.6%) in group F sheep than group P (p = 0). Cardiac index (mean ± SD mL kg⁻¹ minute⁻¹) was significantly (p = 0.012) lower in group F (90 ± 15) than group P (102 ± 35). Other measured cardiorespiratory parameters did not differ statistically significantly between groups. Recovery times and recovery quality were statistically similar in both groups.Conclusions and clinical relevanceFentanyl reduced isoflurane requirements without clinically affecting the cardiorespiratory stability or post-operative recovery in anaesthetized sheep undergoing orthopaedic surgery.     

Combined xylazine and ketamine as an analgesic regimen in sheep

OBJECTIVE: To determine whether low dose xylazine with ketamine reduces the concentrations of cortisol and prolactin in sheep postoperatively and to characterise the effects of the drugs on behaviour during recovery. DESIGN: Analysis of variance was used to compare the effects of anaesthesia, surgery and combined ketamine/xylazine treatment on the plasma cortisol and prolactin concentrations and on behavioural variables in pregnant ewes subjected to abdominal surgery. PROCEDURE: Twelve ewes were randomly assigned to receive either ketamine/xylazine or placebo in association with anaesthesia and surgery. Both groups of ewes underwent anaesthesia alone followed a week later by anaesthesia with laparotomy and hysterotomy. Plasma cortisol and prolactin concentrations were assayed during these procedures and for 5 days afterwards. Behavioural observations were made remotely during recovery from anaesthesia and anaesthesia plus surgery. RESULTS: The concentrations of cortisol in the plasma of pregnant ewes undergoing surgery were increased by preoperative handling and the onset of thiopentone/halothane anaesthesia, with a further increase during surgery (P = 0.033). Cortisol concentrations decreased over the first four postoperative hours (P = 0.029) and were normal by 24 h. The drug treatment did not affect the immediate responses of ewes to anaesthesia or surgery, although treated ewes had lower cortisol concentrations than saline-treated controls over the first five postoperative days (P = 0.018). Prolactin concentrations increased in response to anaesthesia (P = 0.047), but were not affected by surgery or the drug treatment. Drug-treated ewes had prolonged sleeping time after surgery (P = 0.002), but they took no longer to stand than saline-treated controls and required fewer attempts to stand successfully (P = 0.025). CONCLUSION: At the doses used, ketamine and xylazine did not mitigate the immediate endocrine consequences of surgery but the behavioural data provide a basis for further investigations that may lead to improvements in analgesic treatments.     

Measurement of the puncture profile and extradural pressure of cattle during extradural anaesthesia

ObjectiveTo measure the pressure profile during caudal extradural puncture and subsequent extradural anaesthesia in cattle and to investigate the presence of extradural pressure waves.Study designProspective experimental study.AnimalsEleven cattle aged 4.1 ± 2.5 years (range 0.8 to 8.8 years), with a body weight of 613 ± 162 kg (range 302–840 kg).MethodsCaudal extradural puncture was performed. To measure the extradural pressure profile, the needle was connected to an electronic pressure transducer placed at the height of the base of the tail. The pressure profile was recorded for 3 minutes following extradural puncture. Lack of resistance to injection of saline was assessed. One minute and 10 minutes after extradural anaesthesia with procaine extradural pressure was recorded. Correct extradural needle placement was assessed by clinical response.ResultsThree minutes after extradural puncture the median pressure was ?16 (range ?25 to 25) mmHg. Pressure in the extradural space 1 minute after the lack of resistance, 3 seconds after injection, and 10 minutes after injection was ?15 (?24 to 33) mmHg, 8 (?17 to 84) mmHg, and ?7 (?25 to 27) mmHg respectively. Pressure waves were visible after puncture, after lack of resistance, 3 seconds and 10 minutes after injection, in 4, 6, 8 and 7 cattle respectively. Pressure after testing lack of resistance, after the injection of local anaesthetic, as well as at the end of the measurement, period was significantly higher than baseline. All cattle showed clinical signs indicative of successful extradural needle placement.Conclusion and clinical relevance Extradural pressure was sub-atmospheric in 82% of the animals. Pressure waves were not consistently present before or after extradural injection, which limits their usefulness to confirm correct extradural needle placement. Extradural pressures increase significantly after injection of local anaesthetic solution. However, the clinical significance of the increase in extradural pressures was not clear.     

Sedative and analgesic effects of intravenous xylazine and tramadol on horses

This study was performed to evaluate the sedative and analgesic effects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p < 0.05). RT and IAP also significantly increased with T treatment (p < 0.05). CRT did not change significantly with any treatments. The onset of sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended.     

Antinociceptive and selected physiological effects of morphine and xylazine on tiletamine‐zolazepam anesthesia in llamas

ObjectiveEvaluate antinociception, anesthesia, and recovery in llamas given tiletamine-zolazepam (TZ) with either morphine, xylazine, morphine and xylazine, or saline.Study designRandomized crossover experimental study.AnimalsSix healthy, adult intact male llamas.MethodsLlamas were given each of four treatments intramuscularly with a 1-week washout: TZ (2 mg kg^?1) combined with either morphine (0.5 mg kg^?1; M), xylazine (0.15 mg kg^?1; X), morphine (0.5 mg kg^?1) and xylazine (0.15mg kg^?1) (MX), or saline (C). Llamas breathed room air during the experiment. Characteristics of anesthesia, recovery, and selected cardiopulmonary variables were recorded. Antinociception was assessed by clamping a claw at 5-minute intervals. Data were analyzed using a mixed-model anova and Tukey-Kramer test, and are expressed as least squares mean ± SEM. Significance was set at p < 0.05.ResultsNo llama in the control group demonstrated antinociception. Antinociception was longest with treatment MX, followed by treatments X and M, respectively. Heart rates in llamas given treatments X and MX were significantly lower than with other treatments. The respiratory rate in llamas given treatment C was greater (p < 0.05) than for all other treatments, however, the respiratory rate was not significantly different among treatments X, M and MX. The PaO₂ for llamas given MX remained <60 mmHg throughout the 20 minute period of blood gas analysis. Mean arterial blood pressure in llamas in treatment MX was less than for treatments M or C.Conclusion and clinical relevanceThe combination of morphine (0.5 mg kg^?1) and xylazine (0.15 mg kg^?1) increased the duration of antinociception compared with xylazine alone, in TZ-anesthetized llamas. Treatments X, M and MX were associated with hypoxemia (PaO₂ < 60 mmHg).     

Antinociceptive,physiologic and biochemical effects of electroacupuncture combined with xylazine in hybrid goats

ObjectiveTo elucidate the antinociceptive, physiologic and biochemical effects of electroacupuncture (EA) and xylazine in hybrid goats.Study designProspective experimental study.AnimalsA total of 30 female hybrid goats aged 1–2 years and weighing 25 ± 2.9 kg (mean ± standard deviation).MethodsThe goats were divided into five groups and administered xylazine (0.1 mg kg⁻¹; group XYL.1), xylazine (0.3 mg kg⁻¹; group XYL.3), EA (group EA), EA + xylazine (0.1 mg kg⁻¹; group XYL.1-EA) and 0.9% saline (0.3 mL; control group CON). Nociceptive threshold and serum glucose concentration were measured at time 0 and at 15, 30, 45, 60 minutes and 24 hours after treatment. Nociceptive threshold was measured by passing potassium ions through the skin using potassium iontophoresis. Mean arterial pressure (MAP), heart rate (HR), respiratory frequency (f_R) and rectal temperature (RT) were recorded at times 0 and at 5, 10, 15, 20, 30, 45, 60 minutes and 24 hours. Repeated-measures analyses were performed for each response variable; p < 0.05 was considered significant for all analyses.ResultsAntinociceptive effects in groups XYL.1 and XYL.3 were increased significantly at 15–60 minutes compared with group CON. Antinociceptive effect was higher in group XYL.1-EA than groups XYL.1 or EA at 15–60 minutes (p < 0.05). No significant difference in the nociceptive threshold was recorded in groups XYL.1-EA and XYL.3, except at 30 minutes. HR, MAP, f_R, RT values were higher in group XYL.1-EA than in groups XYL.1 or XYL.3. Serum glucose concentration was higher in group XYL.3 at 15–60 minutes than in CON.Conclusions and clinical relevanceThe XYL.1 and EA combination was effective for antinociception with minimum physiologic alteration, suggesting that the combination may be a new and effective strategy for pain relief during clinical procedures in goats.     

Comparison of lidocaine, xylazine, and lidocaine−xylazine for caudal epidural analgesia in cattle

Objective To directly compare the time to onset and duration of analgesia produced by a lidocaine/xylazine combination with that produced by lidocaine and xylazine administered alone in the caudal epidural space of dairy cattle. Design Prospective randomized experimental study. Animals Nine adult (> 4 years of age) dairy cows (520–613 kg). Methods Caudal epidural analgesia was produced in all cows with 2% lidocaine (0.22 mg kg^?1; 5.5 mL 500 kg^?1), 10% xylazine (0.05 mg kg^?1 diluted to 5.5 mL 500 kg^?1 with sterile water), and 2% lidocaine/10% xylazine (0.22 mg kg^?1/0.05 mg kg^?1; total volume of 5.7 mL 500 kg^?1), at no earlier than weekly intervals in a Latin square design. Time to onset, duration and cranial spread of analgesia were recorded, as were degree of sedation, ataxia and ptyalism. Results No significant difference (p > 0.05) was noted for time (mean ± SEM) of onset of analgesia between lidocaine (4.8 ± 1.0 minutes) and the lidocaine/xylazine combination (5.1 ± 0.9 minutes) but onset of analgesia following xylazine was significantly longer (11.7 ± 1.0 minutes) than either of the other two treatments. Lidocaine/xylazine (302.8 ± 11.0 minutes) produced analgesia of significantly longer duration than that of xylazine (252.9 ± 18.9 minutes) and both the lidocaine/xylazine combination and xylazine alone produced analgesia of significantly longer duration than that produced by lidocaine (81.8 ± 11.8 minutes). In all cattle, xylazine, administered either alone or with lidocaine, induced mild to moderate sedation and ataxia and cutaneous analgesia from the coccyx to T13. Mild ataxia was also present in those cattle receiving lidocaine alone. Conclusion The combination of xylazine and lidocaine produces analgesia of quicker onset and longer duration than xylazine administered alone and of longer duration than lidocaine administered alone. Clinical relevance Utilizing this combination, long‐duration obstetrical and surgical procedures could commence relatively soon after epidural injection and could be completed without re‐administration of anesthetic agents.     

The post-operative analgesic effects of epidurally administered morphine and transdermal fentanyl patch after ovariohysterectomy in dogs

ObjectiveTo investigate the analgesic and side effects of epidural morphine or a fentanyl patch after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsTwenty female mongrel dogs undergoing ovariohysterectomy.MethodsThe dogs were allocated to one of two groups: epidural morphine or transdermal fentanyl patch. Anaesthesia was induced with propofol and maintained with isoflurane. Morphine (0.1 mg kg^?1) was administered epidurally in the epidural morphine group and a transdermal fentanyl patch was applied 24 hours before the operation in the fentanyl patch group.The heart rate, respiratory rate, body temperature, plasma cortisol concentration, and sedation and analgesia scores were recorded during the 24 hour post-operative period. Adverse effects such as vomiting, anorexia, skin reactions, urinary retention, and time to start licking the surgical site were also recorded. p < 0.05 was considered significant. Statistical analyses utilized anova for repeated measures, Friedman tests, Mann-Whitney U-tests and independent sample t-tests as relevant.ResultsPain scores were lower in the epidural group than in the fentanyl group at all post-operative times. The dogs in the epidural morphine group were calm and relaxed, whereas discomfort and vocalization were recorded in the fentanyl patch group. The sedation scores were higher in the fentanyl patch group throughout the 12 hour period. Salivation and anorexia lasted longer in the fentanyl patch group than in the epidural morphine group. Plasma cortisol concentrations were high in the early post-operative period in both groups. The fentanyl patch group had higher cortisol concentrations than the epidural morphine group. Slight erythema was recorded in two dogs when the patches were removed.Conclusion and clinical relevanceEpidurally administered morphine provided better analgesia and caused fewer adverse effects than the fentanyl patch after ovariohysterectomy in dogs.     

Comparative evaluation of sedative and clinical effects of dexmedetomidine and xylazine in dromedary calves (Camelus dromedarius)

ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg⁻¹); treatment DEX, dexmedetomidine (5 μg kg⁻¹); and control treatment, normal saline (0.01 mL kg⁻¹). Sedation scores, heart rate (HR), respiratory rate (f_R), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. f_R decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg^–1) and xylazine (0.2 mg kg^–1) was similar in dromedary calves.     

Yohimbine antagonizes the anaesthetic effects of ketamine–xylazine in captive Indian wild felids

ObjectiveTo determine the effectiveness of yohimbine as an antagonist of ketamine-xylazine anaesthesia in captive Asiatic lions (Panthera leo persica), tigers (Panthera tigris) and leopards (Panthera pardus).Study designProspective clinical trial.AnimalsFifty-two healthy adult lions, 55 adult leopards and 16 adult male tigers.MethodsCaptive wild felids in Indian zoos were anaesthetized with a combination of ketamine (2.2-2.6 mg kg^?1) and xylazine (1.1-1.3 mg kg^?1) using a dart propelled from a blowpipe. Time to onset of anaesthesia, lateral recumbency and induction time were measured, and physiological variables (respiration, heart rate and rectal temperature) were recorded once after the onset of complete anaesthesia. Anaesthesia was antagonized at various time periods with an intravenous administration of either 0.1 or 0.15 mg kg^?1 yohimbine. Onset of arousal and time to complete anaesthetic recovery were recorded.ResultsA total of 123 immobilizations were conducted between 2000 and 2005. Anaesthetic induction was achieved in 15-25 minutes in all animals. Incidents of sudden recovery or life-threatening effects associated with immobilizations were not observed. Yohimbine effectively antagonized anaesthesia in all animals within 10 minutes without any excitatory behaviour compared to control animals. No adverse reactions/side effects to yohimbine were recorded except that a few leopards exhibited seizure-like signs for a short period immediately after yohimbine administration. The duration of anaesthesia had no significant effect on the recovery time in any of the animals.Conclusion and clinical relevanceYohimbine antagonized the xylazine portion of ketamine-xylazine anaesthesia and thereby hastened recovery from anaesthesia in Asiatic lions, tigers and leopards.     

The anti-nociceptive efficacy of low dose intramuscular xylazine in lambs

The anti-nociceptive effects of 50 microg kg(-1)of intramuscular xylazine were examined in seven lambs of 4-6 weeks of age using an electrical nociceptive testing method. Lamb anti-nociception increased from an average baseline of 5.88+/-0.72 mA to an average peak value of 13.66+/-1.49 mA at 21 minutes (mean+/-SEM) after the dose, and remained above baseline for the duration of the experimental period (60 minutes). All values were significantly above baseline from 5 minutes post-xylazine administration onwards. These data were also compared with previously published data from adult sheep undergoing the same treatment. There were no differences in the analgesic response between the adult or lamb groups suggesting xylazine dose requirements scale with bodyweight and are unaffected by age over this range. These findings support the use of xylazine as an effective analgesic in sheep with comparable effects and consistent dosing requirements per unit body weight between adult sheep and lambs.     

The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

Xylazine, the classical α₂‐adrenoceptor (α₂‐AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for α₂‐ARs. Previous pharmacological studies suggested that the α_2A‐AR subtype plays a role in mediating the clinical effects of xylazine; however, these studies were hampered by the poor subtype‐selectivity of the antagonists used and a lack of knowledge of their bioavailability in vivo. Here, we attempted to elucidate the role of the α_2A‐AR subtype in mediating the clinical effects of xylazine by comparing the analgesic and sedative effects of this drug in wild‐type mice with those in α_2A‐AR functional knockout mice using the hot‐plate and open field tests, respectively. Hippocampal noradrenaline turnover in both mice was also measured to evaluate the contribution of α_2A‐AR subtype to the inhibitory effect of xylazine on presynaptic noradrenaline release. In wild‐type mice, xylazine (10 or 30 mg/kg) increased the hot‐plate latency. Furthermore, xylazine (3 or 10 mg/kg) inhibited the open field locomotor activity and decreased hippocampal noradrenaline turnover. By contrast, all of these effects were abolished in α_2A‐AR functional knockout mice. These results indicate that the α_2A‐AR subtype is mainly responsible for the clinical effects of xylazine.     

Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.