Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses

Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg⁻¹ hr⁻¹ for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration–time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (K_e), half-life (t_1/2e), volume of distribution (V_d), and clearance (Cl). Median and range were 0.42 (0.15–0.97)/hr, 1.68 (0.87–4.52) hr, 5.85 (2.10–19.34) L/kg, and 28.7 (19.6–39.5) ml min⁻¹ kg⁻¹, respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (C_max) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.     

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.     

Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol

Objective To evaluate the use of a combination of tiletamine/zolazepam and xylazine (TZX) in collared and white‐lipped peccaries and to compare its efficacy as an anesthetic technique with that of tiletamine/zolazepam and butorphanol (TZB). Study design Prospective experimental trial. Animals Seven white‐lipped peccaries (Tayassu pecari) (four females and three males) and four collared peccaries (Tayasu tajacu) (two males and two females). Methods Animal immobilization was attempted with TZX and TZB (IM) on two different occasions. Heart and respiratory rates (HR, RR), rectal temperature (RT), sedation, muscle relaxation, posture, auditory response and analgesia were evaluated every 15 minutes during immobilization. Induction, anesthesia, standing and walking time were determined after drug administration. Results Doses for white‐lipped peccaries were 1.23 ± 0.26 mg kg^?1 (mean ± SD) of TZ and 1.23 ± 0.26 mg kg^?1 of X, and 1.46 ± 0.09 mg kg^?1 of TZ and 0.14 ± 0.008 mg kg^?1 of B; doses for collared peccaries were 1.51 ± 0.29 mg kg^?1 of TZ and 1.51 ± 0.29 mg kg^?1 of X and 1.68 ± 0.02 mg kg^?1 of TZ and 0.17 ± 0.002 mg kg^?1 of B. In white‐lipped peccaries, both drug combinations provided a smooth induction and good immobilization for more than an hour. Anesthesia and standing times were significantly longer in animals given TZB, whereas walking time was significantly longer in animals given TZX. A significant decrease in HR was observed with both treatments. Respiratory rate decreased significantly with TZX, but the rate remained higher than with TZB. Induction and recovery quality in white‐lipped peccaries was better with TZB than with TZX. Neither protocol provided adequate immobilization in collared peccaries. Conclusion and clinical relevance At the doses described, TZB is effective in providing a long period of immobilization, whereas TZX is adequate for short to medium immobilization in white‐lipped peccaries. Neither drug combination was effective in collared peccaries at the doses given.     

苯恶唑和狄普诺啡对麻醉大鼠血浆、垂体和下丘脑β-内啡肽的影响

用二甲苯胺噻嗪(xylazine)+双氢埃托啡(DHE)腹腔注射麻醉大鼠,30 m in时再腹腔注射苯恶唑(Rx781094)+狄普诺啡(M5050),重新记时,放射免疫分析法测定给药后0、5、10、60、120 m in时大鼠血浆、垂体和下丘脑β-内啡肽(β-EP)的含量。结果表明,Rx781094+M5050能够颉颃xylazine+DHE麻醉大鼠引起血浆β-EP的升高,垂体β-EP的下降和下丘脑β-EP的升高。这3种改变均从5 m in开始,持续至60m in。提示:α2-肾上腺素受体(α2-AR)和阿片受体激动剂组成的麻醉合剂xylazine+DHE对大鼠的镇痛和麻醉过程中,激发了内源性阿片肽β-EP的参与。     

Haemodynamic changes during sedation in ponies

The cardiovascular changes induced by several sedatives were investigated in five ponies with a subcutaneously transposed carotid artery by means of cardiac output determinations (thermodilution technique), systemic and pulmonary artery pressure measurements (direct intravascular method) and arterial blood analysis (blood gases and packed cell volume). The cardiovascular depression (decrease in systemic blood pressure and cardiac output) was long lasting (greater than 90 min) after administration of propionylpromazine (0.08 mg/kg intravenous (i.v.)) together with promethazine (0.08 mg/kg i.v.). The phenothiazine-induced sedation was not optimal. alpha 2-Agonists (xylazine (0.60 mg/kg i.v.) and detomidine (20 micrograms/kg i.v.)) induced initial but transient cardiovascular effects with an increase in systemic blood pressure and a decrease in cardiac output for about 15 min. Second degree atrioventricular blocks and bradycardia were seen during this period. The cardiovascular depression was more pronounced during detomidine sedation. Atropine (0.01 mg/kg i.v.) induced a tachycardia with a decrease in stroke volume but did not alter the cardiac output or other cardiovascular parameters. It prevented the occurrence of the bradycardia and heart blocks normally induced by xylazine or detomidine. Atropine potentiated the initial hypertension induced by the alpha 2-agonistic sedatives (especially detomidine). The decrease in cardiac output induced by xylazine, and to a lesser extent by detomidine, was partially counteracted when atropine was given in advance. The atropine-xylazine combination seemed the best premedication protocol before general anaesthesia as it only resulted in minor and transient cardiovascular changes.     

Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses‐ a controlled clinical trial

ObjectivesTo determine the influence of ketamine or xylazine constant rate infusions on isoflurane requirements, cardiovascular parameters and quality of anaesthesia in horses undergoing elective surgery.Study designProspective, matched paired clinical trial.AnimalsFifty four adult Warmblood horses.MethodsAfter premedication with acepromazine, xylazine and butorphanol, anaesthesia was induced with ketamine-midazolam and maintained with isoflurane alone (I), isoflurane with either 1 mg kg⁻¹ hour⁻¹ ketamine (IK) or same dose of xylazine (IX). End tidal concentration of isoflurane (Fe’Iso) was adjusted by the same anaesthetist in all horses according to a scoring system. Dobutamine was infused to maintain mean arterial pressure (MAP) =70 mmHg. Arterial blood gases, heart rate (HR), respiratory rate, MAP and cardiac output (lithium dilution) were measured. Groups I and IK received xylazine before recovery. Recovery quality was scored.ResultsMean ± SD averaged Fe’Iso (volume%) was significantly lower in IX (0.95 ± 0.07) and IK (0.97 ± 0.08) than in I (1.16 ± 0.13). In group IX, HR was significantly lower and averaged MAP (90 ± 13 mmHg) significantly higher than in groups I (71 ± 7 mmHg) and IK (76 ± 7 mm Hg). Differences in other cardiopulmonary variables did not reach statistical significance. All horses recovered well with best score in group IX.ConclusionsBoth CRIs of xylazine and of ketamine resulted in pronounced reduction of isoflurane requirements and blood pressure support based on routinely monitored parameters. Cardiac output appeared well maintained in all three protocols, but lithium dilution induced errors mean the results are untrustworthy. The work requires repetition with another mode of measurement of cardiac output.Clinical relevanceAll three protocols provided good clinical anaesthesia with clinically acceptable cardiovascular effects.     

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).     

盐酸塞拉嗪对大鼠不同脑区Gln及AsP含量的影响

研究盐酸塞拉嗪麻醉下大鼠不同脑区兴奋性氨基酸类神经递质含量的变化,探讨盐酸塞拉嗪中枢麻醉作用的可能机理.将48只Wistar大鼠随机分成6组,分别为对照组、诱导组、麻醉组、恢复Ⅰ组、恢复Ⅱ组和恢复Ⅲ组.采用反向高效液相色谱法测定各脑区Glu和Asp的含量.结果表明:腹腔注射盐酸塞拉嗪40 mg·kg-1后,麻醉组大鼠海马和丘脑Glu、Asp的含量显著降低(P＜0.05或P＜0.01),而小脑和大脑皮质Glu、Asp的含量显著增加(P＜0.01);恢复Ⅰ组除脑干外其它各脑区Glu和Asp的含量与对照组比较差异显著(P＜0.05);恢复Ⅱ组各脑区Glu和Asp的含量均恢复显著(P＞0.05);麻醉全程,脑干内Glu和Asp含量均无显著变化(P＞0.05).结果提示,盐酸塞拉嗪对海马、丘脑、小脑和大脑皮质内Glu、Asp含量的影响可能是其产生全麻作用的重要机理之一.盐酸塞拉嗪的中枢麻醉作用,可能与降低海马和丘脑内Glu、Asp,增加小脑和大脑皮质内Glu、Asp的含量有关,海马可能是盐酸塞拉嗪作用的最敏感的脑区.