A comparison of sedative effects of xylazine alone or combined with levomethadone or ketamine in calves prior to disbudding

ObjectiveTo compare the sedative effects of intramuscular xylazine alone or combined with levomethadone or ketamine in calves before cautery disbudding.Study designRandomized, blinded, clinical trial.AnimalsA total of 28 dairy calves, aged 21 ± 5 days and weighing 61.0 ± 9.3 kg (mean ± standard deviation).MethodsCalves were randomly allocated to three groups: xylazine (0.1 mg kg^–1) and levomethadone (0.05 mg kg^–1; group XL), xylazine (0.1 mg kg^–1) and ketamine (1 mg kg^–1; group XK) and xylazine alone (0.2 mg kg^–1; group X). Local anaesthesia (procaine hydrochloride) and meloxicam were administered subcutaneously 15 minutes after sedation and 15 minutes before disbudding. The calves’ responses to the administration of local anaesthesia and disbudding were recorded. Sedation was assessed at baseline and at intervals up to 240 minutes postsedation. Times of recumbency, first head lift and first standing were recorded. Drug plasma concentrations were measured.ResultsData were obtained from 27 animals. All protocols resulted in sedation sufficient to administer local anaesthesia and to perform disbudding. Sedation scores significantly correlated with drug plasma concentrations (p ≤ 0.002). Times to recumbency did not differ among protocols (2.8 ± 0.3, 3.1 ± 1.1 and 2.1 ± 0.8 minutes for groups XL, XK and X, respectively), whereas interval from drug(s) administration until first head lift was significantly shorter in group XK than X (47.3 ± 14.1, 34.4 ± 5.3 and 62.6 ± 31.9 minutes for groups XL, XK and X, respectively). The area under the time-sedation curve was significantly greater in group X than XK or XL (754 ± 215, 665 ± 118 and 1005 ± 258 minutes for groups XL, XK and X, respectively).Conclusions and clinical relevanceLevomethadone or ketamine with a low dose of xylazine produced short but sufficient sedation for local anaesthesia and disbudding with minimum resistance.     

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.     

Comparison of isoflurane inhalation anaesthesia, injection anaesthesia and high volume caudal epidural anaesthesia for umbilical surgery in calves; metabolic, endocrine and cardiopulmonary effects

ObjectiveTo compare three anaesthetic protocols for umbilical surgery in calves regarding adequacy of analgesia, and cardiopulmonary and hormonal responses.Study designProspective, randomised experimental study.AnimalsThirty healthy German Holstein calves (7 female, 23 male) aged 45.9 ± 6.4 days.MethodsAll calves underwent umbilical surgery in dorsal recumbency. The anaesthetic protocols were as follows: group INH (n = 10), induction 0.1 mg kg^?1 xylazine IM and 2.0 mg kg^?1 ketamine IV, maintenance isoflurane in oxygen; Group INJ (n = 10), induction 0.2 mg kg^?1 xylazine IM and 5.0 mg kg^?1 ketamine IV, maintenance 2.5 mg kg^?1 ketamine IV every 15 minutes or as required; group EPI (n = 10), high volume caudal epidural anaesthesia with 0.2 mg kg^?1 xylazine diluted to 0.6 mL kg^?1 with procaine 2%. All calves received peri-umbilical infiltration of procaine and pre-operative IV flunixin (2.2 mg kg^?1). Cardiopulmonary variables were measured at preset intervals for up to 2 hours after surgery. The endocrine stress response was determined. Intra-operative nociception was assessed using a VAS scale. Data were compared between groups using appropriate statistical tests. A value of p < 0.05 was considered significant.ResultsAll three protocols provided adequate anaesthesia for surgery although, as judged by the VAS scale, intra-operative response was greatest with INJ. Lowest mean cortisol levels during surgery occurred in EPI. Heart rate and cardiac output did not differ between groups, but mean arterial blood pressure, systemic vascular resistance, and partial pressure of carbon dioxide were higher and arterial pH lower in groups INH and INJ than in Group EPI. Group INJ became hypoxaemic and had a significantly greater vascular shunt than did the other groups.Conclusion and clinical relevanceGroups INH and EPI both proved acceptable protocols for calves undergoing umbilical surgery, whilst INJ resulted in variable anti-nociception and in hypoxaemia. High volume caudal epidural anaesthesia provides a practical inexpensive method of anaesthesia for umbilical surgery.     

Effect of sub-anesthetic xylazine and ketamine ('ketamine stun') administered to calves immediately prior to castration

ObjectiveTo describe the pharmacokinetics, cortisol response and behavioral changes associated with administration of sub-anesthetic xylazine and ketamine prior to castration.Study designProspective, randomized experiment.AnimalsTwenty-two male beef calves (260-310 kg).MethodsCalves were randomly assigned to receive the following treatment immediately prior to surgical or simulated castration; 1) uncastrated, placebo-treated control (CONT) (n = 4), 2) Castrated, placebo treated control (CAST) (n = 6), 3) castrated with intravenous xylazine (X) (0.05 mg kg^?1) (n = 6), and 4) castrated with IV xylazine (X) (0.05 mg kg^?1) combined with ketamine (K) (0.1 mg kg^?1) (n = 6). Blood samples collected over 10 hours post-castration were analyzed by LC-MS-MS for drug concentrations and chemiluminescent immunoassay for cortisol determination.ResultsDrug concentrations during the first 60 minutes post-castration fit a one-compartment open model with first-order elimination. The harmonic mean elimination half-lives (± pseudo SD) for X, X with K and K were 12.9 ± 1.2, 11.2 ± 3.1 and 10.6 ± 2.8 minutes, respectively. The proportion of the total area under the effect curve (AUEC) for cortisol during this period was significantly lower in the X group (13 ± 3%; p = 0.006) and the X+K group (14 ± 2%; p = 0.016) compared with the CAST calves (21 ± 2%). However, after 300 minutes the AUEC in the X group was higher than CAST. Significantly more calves demonstrated attitude that was unchanged from pre-manipulation behavior in the CONT (p = 0.021) and X+K treated calves (p = 0.0051) compared with the CAST calves.ConclusionsBehavioral changes and lower serum cortisol concentrations during the first 60 minutes post-castration were associated with quantifiable xylazine and ketamine concentrations.Clinical relevanceLow doses of xylazine and ketamine administered immediately prior to castration may offer a safe, efficacious and cost-effective systemically administered alternative or adjunct to local anesthesia.     

Evaluation of the isoflurane-sparing effects of lidocaine infusion during umbilical surgery in calves

ObjectiveTo evaluate the isoflurane-sparing effects of lidocaine administered by constant rate infusion (CRI) during umbilical surgery in calves.Study designRandomized ‘blinded’ prospective clinical study.AnimalsThirty calves (mean 4.7 ± SD 2.5 weeks old) undergoing umbilical surgery.MethodsAfter premedication with xylazine (0.1 mg kg^?1, IM), anaesthesia was induced with ketamine (4 mg kg^?1, IV) and maintained with isoflurane in O₂ administered through a circle breathing system. The calves were assigned randomly to receive a bolus of 2 mg kg^?1 lidocaine IV after induction of anaesthesia, followed by CRI of 50 μg kg^?1 minute^?1 (group L, n = 15) or a bolus and CRI of 0.9% sodium chloride (NaCl, group S, n = 15). End-tidal isoflurane was adjusted to achieve adequate depth of anaesthesia. Heart rate, direct arterial blood pressure and body temperature were measured intraoperatively. Groups were compared by t- tests, anova or Mann–Whitney rank sum test as appropriate.ResultsThe end-tidal concentration of isoflurane (median, IQR) was significantly lower in group L [1.0% (0.94–1.1)] compared to group S [1.2% (1.1–1.5)], indicating a 16.7% reduction in anaesthetic requirement during lidocaine CRI. Cardiopulmonary parameters and recovery times did not differ significantly between groups.Conclusion and clinical relevanceLidocaine CRI may be used as a supplement to inhalation anaesthesia during umbilical surgery in calves in countries where such a protocol would be within the legal requirements for veterinary use in food animals. This study did not show any measurable benefit to the calves other than a reduction in isoflurane requirement.     

Tramadol improved the efficacy of ketamine–xylazine anaesthesia in young pigs

ObjectiveTo evaluate the influence of premedication with tramadol on xylazine–ketamine anaesthesia in young pigs.Study designProspective, randomized, blinded cross-over study.AnimalsTen young Niger hybrid pigs: mean weight 6.1 ± 0.6 kg.MethodsPigs were anaesthetized twice. Xylazine (2.5 mg kg^?1), ketamine (25 mg kg^?1) and atropine (0.04 mg kg^?1) were administered by intramuscular (IM) injection, 5 minutes after either tramadol (5 mg kg^?1)) (treatment XKT) or saline (treatment XKS). Time to loss of righting reflex (TLRR), duration of antinociception, duration of recumbency (DR) and recovery times (RCT) were recorded. Quality of induction of anaesthesia including ease of endotracheal intubation was assessed using a subjective ordinal rating score of 1 (worst) to 4 (best). Heart, pulse and respiratory rates, arterial oxygen saturations and rectal temperatures were determined over 60 minutes. Antinociception was assessed by the pigs’ response to artery forceps applied at the interdigital space. Data were compared with Student's t-test, Mann–Whitney's test or analysis of variance (anova) for repeated measures as appropriate and are presented as mean ± standard deviation.ResultsThe quality of anaesthetic induction was significantly better and duration of antinociception significantly longer (p < 0.05) in treatment XKT (3.1 ± 0.7 score; 43.7 ± 15.5 minutes) than in treatment XKS (2.8 ± 0.6 score; 32.0 ± 13.3 minutes). TLRR, DR and RCT did not differ significantly (p > 0.05) between treatment XKT (2.1 ± 0.8, 65.8 ± 17.0 and 13.2 ± 6.7 minutes) and treatment XKS (2.1 ± 1.3, 58.0 ± 14.8 and 10.3 ± 5.6 minutes). Physiological measurements did not differ between the treatments.Conclusion and clinical relevanceTramadol improved the quality of anaesthetic induction and increased the duration of antinociception in xylazine–ketamine anaesthetized young pigs without increasing duration of anaesthesia, nor causing additional depression of the physiological parameters measured.     

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg^?1 IV). Twenty minutes later they received xylazine (1 mg kg^?1 IV), then after 5 minutes, guaiphenesin (35 mg kg^?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg^?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t_1/2), plasma clearance (Clp) and volume of distribution (V_d) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute^?1 kg^?1 and 1.6 ± 0.4 L kg^?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.     

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.     

Antinociceptive, sedative and cardiopulmonary effects of subarachnoid and epidural xylazine-lidocaine in xylazine-sedated calves

ObjectiveTo evaluate the antinociceptive, sedative and cardiopulmonary effects of subarachnoid and epidural administration of xylazine-lidocaine in xylazine-sedated calves.Study designProspective, crossover study.AnimalsSix clinically healthy Holstein calves.MaterialsThe calves were allocated randomly to receive two treatments, subarachnoid or epidural xylazine (0.025 mg kg^?1)–lidocaine (0.1 mg kg^?1) diluted to a total volume of 5 mL with physiological saline. Prior to either epidural or subarachnoid injection, sedation was induced in all calves by intravenous administration of 0.1 mg kg^?1 xylazine. The quality and duration of antinociception and sedation were monitored. Areas of the cranial abdomen, umbilicus, and caudal abdomen were evaluated for antinociception using pinprick tests with a scoring system of 0–3 (0, none; 1, mild; 2, moderate; 3, complete). Sedation was assessed by using a 4-point scale (0, none; 1, mild; 2, moderate; 3, deep). The following cardiopulmonary variables were monitored: heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), blood pH, arterial partial pressure of oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂), bicarbonate (HCO₃), base excess (BE), and oxygen saturation (SaO₂).ResultsXylazine sedation and subarachnoid xylazine-lidocaine resulted in significantly higher nociceptive block than the epidural technique. Moreover, subarachnoid xylazine-lidocaine induced a significantly longer duration of complete antinociception (median [IQR]) in the cranial abdomen (15.0 [15.0–30.0] versus 7.5 [1.3–10.0] minutes; p < 0.05) and umbilicus (45.0 [32.5–57.5] versus 10.0 [6.3–17.5] minutes; p < 0.05) compared with epidural xylazine-lidocaine. There was moderate sedation with both techniques. In both treatments, blood pH, MAP and PaO₂ decreased significantly, and PaCO₂ increased significantly during anaesthesia. No change was evident in HR, f_R, HCO_3, BE, or SaO₂.Conclusion and clinical relevanceThe subarachnoid injection provided better quality and longer duration of antinociception than epidural administration of the same doses of xylazine-lidocaine in xylazine-sedated calves, while cardiopulmonary depressant effects were observed with both regimens.     

Cardiopulmonary effects during anaesthesia induced and maintained with propofol in acepromazine pre‐medicated donkeys

ObjectiveTo evaluate the cardiopulmonary effects of anaesthesia induced and maintained with propofol in acepromazine pre-medicated donkeys.Study designProspective experimental study.AnimalsSix healthy male donkeys weighing 78–144 kg.MethodsDonkeys were pre-medicated with intravenous (IV) acepromazine (0.04 mg kg⁻¹). Ten minutes later, anaesthesia was induced with IV propofol (2 mg kg⁻¹) and anaesthesia maintained by continuous IV infusion of the propofol (0.2 mg kg⁻¹ minute⁻¹) for 30 minutes. Baseline measurements of physiological parameters, and arterial blood samples were taken before the acepromazine administration, then 5, 15, 30, 45, and 60 minutes after the induction of anaesthesia. Changes from baseline were analysed by anova for repeated measures.ResultsWhen compared with baseline (standing) values, during anaesthesia heart rate increased throughout: significant at 5 (p = 0.001) and 15 (p = 0.015) minutes. Mean arterial blood pressure increased significantly only at 15 minutes (p < 0.001). Respiratory rate and arterial pH did not change significantly. PaO₂ was lower throughout anaethesia, but this only reached significance at 15 minutes (p = 0.041). PaCO₂ was statistically (but not clinically) significantly reduced at the times of 30 (p = 0.02), 45 (p = 0.01) and 60 (p = 0.04). Rectal temperature decreased significantly at all times of the study.Conclusions and clinical relevanceAdministration of propofol by the continuous infusion rate for the maintenance of anaesthesia resulted in stable cardiopulmonary effects and could prove to be clinically useful in donkeys.     

Cardiopulmonary effects of combined xylazine-guaiphenesin-ketamine infusion and extradural (inter-coccygeal lidocaine) anaesthesia in calves

Objective To investigate the cardiopulmonary effects of a xylazine–guaiphenesin–ketamine infusion combined with inter‐coccygeal extradural (lidocaine) anaesthesia in calves. Study design Prospective study. Animals Five Holstein Friesian calves (one steer, four heifers) aged 6 weeks weighing 65.2 ± 2.7 kg. Materials and methods Calves were anaesthetized with isoflurane in oxygen for instrumentation. At least 12 hours later, xylazine (0.2 mg kg^?1 IM) was given. After 15 minutes, an infusion of xylazine hydrochloride (0.1 mg mL^?1), guaiphenesin (50 mg mL^?1) and ketamine (1 mg mL^?1) (X–G–K) was infused at a rate of 1.1 mL kg^?1 hour^?1 IV. Oxygen (4 L minute^?1) was delivered by nasotracheal tube 30 minutes later. Inter‐coccygeal (Co₁–Co₂) extradural anaesthesia (lidocaine 2%, 0.18 mL kg^?1) was administered 30 minutes later. Cardiopulmonary variables were obtained in the unsedated standing calves 10 minutes after xylazine, 15 and 30 minutes after X–G–K without O₂, 15 and 30 minutes after X–G–K with O₂ and 5, 15, 30, 45 and 60 minutes after extradural anaesthesia. Data were analysed using a repeated measurement analysis of variance including an autoregressive covariance structure of order 1 (correlations at different time intervals). Results Xylazine caused significant (p < 0.05) decreases in heart rate (HR), cardiac output (Qt) and index (CI), stroke volume and stroke index, mean, systolic and diastolic arterial blood pressure (MAP, SAP, DAP), left (LVWSI) and right ventricular stroke work index (RVWSI), mean, systolic and diastolic pulmonary arterial pressure (MPAP, SPAP, DPAP), arterial pH, arterial oxygen tension (P_aO₂), arterial base excess, arterial HCO₃^? concentration, arterial saturation, packed cell volume, arterial and venous oxygen content (C_aO₂, C_vO₂), O₂ consumption and O₂ delivery (V?O₂, ?O₂). Increases in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were observed. During X–G–K infusion without O₂, HR, Qt and CI increased gradually while SVR, PVR and MAP decreased. Left ventricular stroke work index and P_aO₂ remained constant, while O₂ supplementation improved P_aO₂. Coccygeal extradural anaesthesia had little effect on cardiopulmonary variables. Respiratory rate (f) and P_aCO₂ significantly increased over the experiment. Conclusions and clinical relevance Xylazine caused adverse cardiopulmonary effects in calves. Improvement occurred during xylazine–guiaphenesin–ketamine infusion. Cardiac index and arterial blood pressure remained below baseline values while sustained increases in respiration rate and P_aCO₂ were observed. Inter‐coccygeal extradural anaesthesia had only minor effects. Oxygen supplementation proved advantageous during guiaphenesin, ketamine and xylazine infusion in healthy calves in combination with coccygeal extradural anaesthesia induced persistent cardiopulmonary depression.     

Plasma histamine concentrations in horses administered sodium penicillin,guaifenesin–xylazine–ketamine and isoflurane with morphine or butorphanol

ObjectiveVarious drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions.Study designProspective studies with one randomized.AnimalsA total of 44 client-owned horses.MethodsIn one study, anesthesia was induced with xylazine followed by ketamine–diazepam. Anesthesia was maintained with guaifenesin–xylazine–ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg^–1 and 0.1 mg kg^–1 hour^–1; 15 horses) or butorphanol (group B: 0.05 mg kg^–1 and 0.01 mg kg^–1 hour^–1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05.ResultsWith histamine, differences occurred between baseline (3.2 ± 2.4 ng mL^–1) and GXK (5.2 ± 7.1 ng mL^–1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL^–1) and group M (11.1 ± 12.4 ng mL^–1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL^–1) than at 30 minutes (4.9 ± 3.1 ng mL^–1) and 60 minutes (4.0 ± 2.5 ng mL^–1). Histamine correlated with morphine at 2, 30 and 60 minutes.Conclusions and clinical relevanceGXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.     

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.     

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.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

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.     

Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin

ObjectiveTo compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin.Study designRandomized blinded cross-over experimental study.AnimalsSix adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings.MethodsEach horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg^?1 or alfaxalone 1 mg kg^?1. Premedication was with xylazine 0.5 mg kg^?1 and guaifenesin 35 mg kg^?1. Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO₂) and carbon dioxide (PaO₂), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range).ResultsThere was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24–47) minutes for alfaxalone; 22 (18–35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38–67) minutes] compared with ketamine [35 (30–47)]. There was no statistical difference between treatments in effect on HR, PaO₂ or PaCO₂ although for both regimens, PaO₂ decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure.Conclusions and clinical relevanceBoth alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.     

The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation,ataxia and response to stimuli in horses

ObjectiveTo compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli.Study designBlinded randomized experimental cross-over study.AnimalsTen adult horses.MethodsDegree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading doses of xylazine (1 mg kg^?1) or romifidine (80 μg kg^?1) administered over 3 minutes, immediately followed by a CRI of xylazine (0.69 mg kg^?1 hour^?1) or romifidine (30 μg kg^?1 hour^?1) which was administered for 120 minutes. Degree of sedation, PI, A and reaction to the different stimuli were measured at different time points before, during and for one hour after discontinuing drug administration. Data were analysed using two-way repeated measures anova, a Generalized Linear Model and a Wilcoxon Signed Rank Test (p < 0.05).ResultsSignificant changes over time were seen for all variables. With xylazine HHAG was significantly lower 10 minutes after the loading dose, and higher at 150 and 180 minutes (i.e. after CRI cessation) compared to romifidine. Reaction to acoustic stimulation was significantly more pronounced with xylazine. Reaction to visual stimulation was greater with xylazine at 145 and 175 minutes. PI was consistently but not significantly greater with xylazine during the first 30 minutes. Reaction to touch and A did not differ between treatments. Compared to romifidine, horses were more responsive to metallic noise with xylazine.ConclusionsTime to maximal sedation and to recovery were longer with romifidine than with xylazine.Clinical relevanceWith romifidine sufficient time should be allowed for complete sedation before manipulation.     

Chemical restraint of African mole‐rats (Fukomys sp.) with a combination of ketamine and xylazine

ObjectiveTo establish an accurate anaesthetic dose for chemical restraint of African mole-rats using ketamine and xylazine.Study designProspective nonrandomized laboratory study.AnimalsSixteen adult Ansell’s mole-rats (Fukomys anselli) and eight giant mole-rats (F. mechowii).MethodsFukomys anselli of different ages, sexes and reproductive status were systematically anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg⁻¹) and increasing the doses in steps of 0.5 mg kg⁻¹ until loss of the righting reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine, starting at 0.5 mg kg⁻¹ that was increased by 0.5 mg kg⁻¹ in further trials. Once an effective combination was established and evaluated in F. anselli, it was also tested in F. mechowii. Heart and respiratory rates and rectal temperatures were measured during anaesthesia. anova for repeated measures and Student’s t-test were used to compare means.ResultsChemical restraint was accomplished at a dose of 6 mg kg⁻¹ ketamine combined with 2.5 mg kg⁻¹ xylazine. LRR lasted on average mean 56 ± SD 19 minutes (F. anselli) and 140 ± 41 minutes (F. mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 ± 15 minutes (F. anselli) and for 29 ± 2 minutes (F. mechowii), respectively. All animals recovered satisfactorily. Heart and respiratory rates were stable during anaesthesia, but rectal temperature fell significantly in F. mechowii after losing the righting reflex (LRR) from T1 (32.6 ± 0.6 °C) to T3 (30.4 ± 0.9 °C).Conclusions and Clinical relevanceAfrican mole-rats (Bathyergidae) live in closed burrow systems under particular conditions (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several physiological adaptations. Injectable anaesthetics in the dose rates used in other rodents are not appropriate for use in these subterranean species. Here, a reliable protocol for chemical restraint is provided.     

Evaluation of xylazine–alfaxalone anesthesia for field castration in donkey foals

ObjectiveTo evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration.Study designProspective clinical study.AnimalsA group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg.MethodsDonkeys were anesthetized with xylazine (1 mg kg⁻¹) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg⁻¹) IV. Additional doses of xylazine (0.5 mg kg⁻¹) and alfaxalone (0.5 mg kg⁻¹) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute⁻¹. Heart rate (HR), respiratory rate (f_R) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO₂) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent).ResultsMedian (range) induction score was 5 (1–5), and recovery score 4 (1–5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. f_R was decreased at 5 and 10 minutes but was not considered clinically significant. SpO₂ was <90% at one time point in two animals.Conclusions and clinical relevanceXylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.