Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

Reversal of xylazine-induced sedation in dairy calves with atipamezole: A field trial

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139–0.357 mg/kg) induced sedation with complete immobilization in all animals (n=195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10–81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n=11), 10:3 (n=21), 4:1 (n=21) and 5:1 (n=25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n=11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n=7), 4:1 (n=33), 5:1 (n=16), 8:1 (n=27) and 10:1 (n=9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively. The mean time to standing for control animals (n=14) was 88.1 (13.1) min.Animals given high doses of atipamezole (dose ratio groups 5:2 intramuscularly, 10:3 intravenously and 4:1 intravenously) showed signs of excitement while in animals given low doses of atipamezole (dose ratio groups 5:1 intramuscularly and 10:1 intravenously) resedation and relapse into recumbency occurred. Medium doses of atipamezole (dose ratio groups 10:3 intramuscularly, 4:1 intramuscularly, 5:1 intravenously and 8:1 intravenously) did not cause any undesirable side-effects or resedation, and can be recommended for reversal of xylazine-induced sedation in dairy calvesAbbreviations ATI atipamezole-HCl - BW body weight - IM intramuscular - IV intravenous - SD standard deviation - XYL xylazine     

Clinicophysiological Effects of Spinally Administered Ketamine and Its Combination with Xylazine and Medetomidine in Healthy Goats

The study was conducted in 9 healthy adult goats of either sex, weighing 15–20 kg, to evaluate and compare the clinicophysiological effects of spinally administered ketamine alone and in combination with xylazine and medetomidine. Nine trials each of the three treatments were conducted randomly by injecting ketamine (2.5 mg/kg) (n = 9), ketamine and xylazine (2.5 mg/kg and 0.05 mg/kg) (n = 9) and ketamine and medetomidine (2.5 mg/kg and 10 μg/kg) (n = 9). The drugs were administered at the lumbosacral subarachnoid space under strict aseptic conditions. The treatments were evaluated on the basis of clinicophysiological, haematological, biochemical and haemodynamic observations. Ketamine produced mild to moderate analgesia of the hindquarters. Its combination with either xylazine or medetomidine produced complete analgesia of the hindquarters for 45–60 min. Ataxia was moderate in the ketamine group, whereas animals attained sternal recumbency in the combination groups. A moderate degree of sedation was recorded in the combination groups. Heart rate and respiratory rate depression in the combination groups and heart rate and respiratory rate stimulation in ketamine group were recorded. Haematological parameters decreased in all the groups. Increase in serum glucose, creatinine and urea nitrogen was recorded in all the groups. Serum electrolytes did not show any significant change. The results showed that the combination of ketamine with xylazine or medetomidine at these dose rates produced a comparable degrees of analgesia of hindquarters with transient and minimal cardiopulmonary side effects.     

Comparison of xylazine and lidocaine effects for analgesia and cardiopulmonary functions following lumbosacral epidural injection in goats

The present study was carried out in order to compare the effects of xylazine and lidocaine on analgesia and cardiopulmonary parameters following epidural injection in goats. Twelve healthy Small East African goats of both sexes (mean +/- SD; 15.6 +/- 1.9 kg body weight) were used. The goats were randomly assigned to two groups of five and seven animals. The first group (n = 5) was given 2% lidocaine-HCl at 4400 micrograms/kg body weight. The second group (n = 7) was administered 2% xylazine-HCl at 150 micrograms/kg body weight. All drugs were diluted in 5 ml of sterile water and were injected epidurally through the lumbosacral interspace with the injection taking over 20 s. Both drugs induced analgesia within 5 min. Signs of sedation, cardiopulmonary changes and lateral recumbency developed within 5-7 min after administration of epidural xylazine. Tail flaccidity and hind limb paralysis developed 3 min after epidural administration of lidocaine. The time from recumbency to regaining normal stance was 60 and 158 min for xylazine- and lidocaine-treated animals respectively. Xylazine induced adequate analgesia of the flank and perineum, which extended to the head and forelimbs. In contrast, lidocaine induced adequate bilateral flank and perineal analgesia extending up to the third thoracic vertebra. For both drugs, analgesia of the flank and perineum persisted for the entire 180-min observational period. Epidural injection of xylazine and lidocaine caused variable depression effects on the cardiopulmonary values but was not so low as to cause concern. It is concluded that lumbosacral epidural injection of xylazine at 150 micrograms/kg body weight in 5 ml of water for injection offers the most desirable sedation and analgesia of the flank and perineum. The longer duration of analgesia may be useful for postoperative analgesia and relief of continuous straining in goats.     

Xylazine and tiletamine-zolazepam anesthesia in horses

The cardiopulmonary and anesthetic effects of xylazine in combination with a 1:1 mixture of tiletamine and zolazepam were determined in 6 horses. Each horse was given xylazine IV or IM, as well as tiletamine-zolazepam IV on 4 randomized occasions. Anesthetics were administered at the rate of 1.1 mg of xylazine/kg of body weight, IV, 1.1 mg of tiletamine-zolazepam/kg, IV (treatment 1); 1.1 mg of xylazine/kg, IV, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 2); 1.1 mg of xylazine/kg, IV, 2.2 mg of tiletamine-zolazepam/kg, IV (treatment 3); and 2.2 mg of xylazine/kg, IM, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 4). Tiletamine-zolazepam doses were the sum of tiletamine plus zolazepam. Xylazine, when given IV, was given 5 minutes before tiletamine-zolazepam. Xylazine, when given IM, was given 10 minutes before tiletamine-zolazepam. Tiletamine-zolazepam induced recumbency in all horses. Duration of recumbency in group 1 was 31.9 +/- 7.2 (mean +/- 1 SD) minutes. Increasing the dosage of tiletamine-zolazepam (treatments 2 and 3) significantly (P less than 0.05) increased the duration of recumbency. Xylazine caused significant (P less than 0.05) decreases in heart rate and cardiac output and significant (P less than 0.05) increases in central venous pressure and mean pulmonary artery pressure 5 minutes after administration. Respiratory rate was decreased. Arterial blood pressures increased significantly (P less than 0.05) after xylazine was administered IV in treatments 1 and 3, but the increases were not significant in treatment 2. Xylazine administered IM caused significant (P less than 0.05) increases in central venous pressure and significant (P less than 0.05) decreases in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary effects of romifidine/ketamine or xylazine/ketamine when used for short duration anesthesia in the horse

The cardiovascular changes associated with anesthesia induced and maintained with romifidine/ketamine versus xylazine/ ketamine were compared using 6 horses in a cross over design. Anesthesia was induced and maintained with romifidine (100 microg/kg, IV)/ketamine (2.0 mg/kg, IV) and ketamine (0.1 mg/kg/min, IV), respectively, in horses assigned to the romifidine/ ketamine group. Horses assigned to the xylazine/ketamine group had anesthesia induced and maintained with xylazine (1.0 mg/kg, IV)/ketamine (2.0 mg/kg, IV) and a combination of xylazine (0.05 mg/kg/min, IV) and ketamine (0.1 mg/kg/min, IV), respectively. Cardiopulmonary variables were measured at intervals up to 40 min after induction. All horses showed effective sedation following intravenous romifidine or xylazine and achieved recumbency after ketamine administration. There were no significant differences between groups in heart rate, arterial oxygen partial pressures, arterial carbon dioxide partial pressures, cardiac index, stroke index, oxygen delivery, oxygen utilization, systemic vascular resistance, left ventricular work, or any of the measured systemic arterial blood pressures. Cardiac index and left ventricular work fell significantly from baseline while systemic vascular resistance increased from baseline in both groups. The oxygen utilization ratio was higher in the xylazine group at 5 and 15 min after induction. In conclusion, the combination of romifidine/ketamine results in similar cardiopulmonary alterations as a xylazine/ketamine regime, and is a suitable alternative for clinical anesthesia of the horse from a cardiopulmonary viewpoint.     

Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

Toxic algae in some New Zealand freshwater ponds

Trials were conducted to test the ability of yohimbine, 4-aminopyridine and doxapram given by intravenous injection to antagonise xylazine sedation in red deer (Cervus elaphus). Yohimbine produced the best and most consistent result. The mean time taken for 34 animals to stand spontaneously after receiving yohimbine (0.2 to 0.25 mg/kg) was 2 minutes 25 seconds and this occurred, on average, 33 minutes after the initial doze of xylazine. Control deer took 67 and 104 minutes on average to stand after receiving intravenous (0.64–0.96 mg/kg) and intramuscular (1.0–1.5 mg/kg) injections of xylazine respectively. Two deer which received an overdose of xylazine (4 mg/kg) recovered 3 and 9 minutes respectively after receiving yohimbine. Two deer given a high intravenous dose of yohimbine (1.0 mg/kg) became mildly nervous and anxious, but returned to normal within an hour. 4-aminopyridine (0.3 mg/kg) alone produced some arousal from xylazine sedation (0.6–1.0 mg/kg) but was inconsistent. In combination with yohimbine (0.125 mg/kg) it produced rapid recovery in two deer but caused convulsions in two other deer.

Doxapram (1 mg/kg) produced respiratory stimulation and some arousal from xylazine sedation (0.6–1.0 mg/kg) in the majority of deer but the effect was transitory. Animals relapsed into moderate sedation and recumbency within 10 minutes and required vigorous stimulation to arouse them again.

Yohimbine, administered by intravenous injection at a dose rate of 0.2 to 0.25 mg/kg, appears to be a safe and reliable drug for the reversal of xylazine sedation in deer.     

Preliminary findings of altered follicular activity in Holstein cows with coagulation factor XI deficiency

Factor XI (F XI) deficiency is an autosomal recessive coagulopathy found in Holstein cattle. Affected animals have a 50% greater prevalence of repeat breeding. Therefore, several parameters describing ovarian function were studied. Daily blood sampling revealed that progesterone concentrations were slower to decline from a peak at day 16 (p<0.01) to values less than 3 nmol/L in F XI-deficient cows (5.14±0.69 days (mean ± SD) versus 4.05±0.63 days in control animals), resulting in an oestrous cycle length of 24.7±2.1 days compared to 22.9±3.0 days, respectively. This was not due to an alteration in the availability of prostaglandin F₂ (PGF₂) or oxytocin (OT) involved in luteolysis. No significant differences (p>0.05) were seen between normal (n=7) and F XI-deficient (n=7) cows in the peak values or the area under the curve for the pulse in 13,14-dihydro-15-keto PGF₂ in response to OT challenge or in the parameters describing the pulse of ovarian OT secretion after PGF₂ injection (n=7 for each) between days 12 and 14. Ovulatory follicular development was assessed by ultrasound monitoring and plasma 17-oestradiol values at 8-h intervals after a luteolytic injection of cloprostenol (n=6 for each). Follicular diameter was smaller (p<0.05) and accompanied by lower peak oestradiol values near the time of ovulation in F XI-deficient cows. The results suggest that the oestrous cycle in F XI-deficient cows is characterized by a slower process of luteolysis that may be associated with smaller follicular development.Abbreviations F XI factor XI - OT oxytocin - PGF₂ prostaglandin F₂ - PGFM 13,14-dihydro-15-keto-prostaglandin F₂ - i.m. intramuscularly     

Immobilization of mink (Mustela vison) with medetomidine-ketamine and remobilization with atipamezole

Four groups of mink were immobilized with medetomidine-HCl (MED) 0.1 mg/kg + ketamine (KET) 5 or 7.5 mg/kg at different ambient temperatures. The induction time, degree of immobilization and analgesia, rectal temperature, heart and respiration rates were recorded at intervals throughout the immobilization period. The animals were then given atipamezole-HCl (ATI) 0.5 mg/kg for reversal at different times after injection of MED/KET and the effects of the antagonist were evaluated.Subcutaneous administration of MED/KET induced complete immobilization in all 20 animals, and the highest dose was considered suitable for major surgery. Prolonged immobilization at low ambient temperatures (–10 to +5°C) caused severe hypothermia in all animals. The mean rectal temperature had dropped to 37.8°C and 32.1°C at 15 and 85 min, respectively, after injection of MED/KET, significantly lower than the corresponding values for animals immobilized at room temperature.Intramuscular administration of ATI 20 or 40 min after injection of MED/KET rapidly remobilized the animals without apparent side-effects. Administration of ATI to animals recovering spontaneously 90 min after injection of MED/KET induced thermogenesis (shivering) in animals immobilized at a low ambient temperature, while no such effect was seen in animals immobilized at room temperature. One hour after injection of ATI, the rectal temperatures of all treated animals had returned to normal and there were no signs of abnormal behaviour.     

Evaluation of Nociception,Sedation, and Cardiorespiratory Effects of a Constant Rate Infusion of Xylazine Alone or in Combination with Lidocaine in Horses

This study aimed to evaluate the effects of a constant rate infusion (CRI) of xylazine or xylazine in combination with lidocaine on nociception, sedation, and physiologic values in horses. Six horses were given intravenous (IV) administration of a loading dose (LD) of 0.55 mg/kg of xylazine followed by a CRI of 1.1 mg/kg/hr. The horses were randomly assigned to receive three treatments, on different occasions, administered 10 minutes after initiation of the xylazine CRI, as follows: control, physiologic saline; lidocaine low CRI (LLCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.025 mg/kg/min); and lidocaine high CRI (LHCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.05 mg/kg/min). A blinded observer assessed objective and subjective data for 50 minutes during the CRIs. In all treatments, heart and respiratory rates decreased, end-tidal carbon dioxide concentration increased, and moderate to intense sedation was observed, but no significant treatment effect was detected in these variables. Ataxia was significantly higher in LHCRI than in the control treatment at 20 minutes of infusion. Compared with baseline values, nociceptive threshold increased to as much as 79% in the control, 190% in LLCRI, and 158% in LHCRI. Nociceptive threshold was significantly higher in LLCRI (at 10 and 50 minutes) and in LHCRI (at 30 minutes) than in the control treatment. The combination of CRIs of lidocaine with xylazine produced greater increases in nociceptive threshold compared with xylazine alone. The effects of xylazine on sedation and cardiorespiratory variables were not enhanced by the coadministration of lidocaine. The potential to increase ataxia may contraindicate the clinical use of LHCRI, in combination with xylazine, in standing horses.     

A comparison of xylazine-ketamine and detomidine-ketamine anaesthesia in horses

Anaesthesia produced by xylazine (1.1 mg/kg IV) followed in 3–5 minutes by ketamine (2.2 mg/ kg IV) (X / K) was compared to anaesthesia produced by detomidine (0.02 mg/kg IV) followed in 15–25 minutes by ketamine (2.2 mg/kg IV) (D/K) in the same six horses. Quality of induction, recovery, muscle relaxation, coordination (before and after anaesthesia) and response to stimulus were subjectively evaluated. Heart rate, respiratory rate, mean blood pressure, hemoglobin saturation, arterial pH, CO₂ and O₂ were monitored. Recumbency time and number of attempts required to stand were recorded. Recumbency time was longer in all horses with X/K (median recumbency time of 27 min) than with D/K (median recumbency time of 22 min). No significant differences between treatments were seen for any other variable measured, although 2 horses did not appear to reach a surgical plane of anaesthesia with D/K.     

Effect of hot-iron disbudding on behaviour and plasma cortisol of calves sedated with xylazine

We investigated cortisol and behaviour for the first hour after hot-iron disbudding of calves aged 37 ± 4 days: disbudded after i/m xylazine (n = 10); disbudded after i/m xylazine and regional anaesthesia with lidocaine (n = 10); sham-disbudded after xylazine and lidocaine (n = 11); sham-disbudded after i/m saline and lidocaine (n = 10). Xylazine-treated groups had higher cortisol than saline-treated animals and showed no differences among them at any time. Sham-disbudded calves with xylazine had lower cortisol at 60 min compared with all other times. Xylazine-alone disbudded calves struggled more during the procedure than all other groups. Xylazine-alone disbudded calves showed more ear-flicks at 10, 25 and 40 min and head-shakes at 40 min than all other groups. We conclude that cortisol should not be used as an indicator of pain in disbudded calves while under the sedative effect of xylazine and that some behaviours during and after the procedure are useful in showing that xylazine alone does not control hot-iron disbudding pain.     

Acute and Subacute Metabolic and Endocrine Effects of Clenbuterol in Female Pigs

The aim of the study was to assess the relationship between acute and subacute metabolic and endocrine effects after intravenous administration of the ₂-adrenergic agonist clenbuterol in a growth-promoting dose to female pigs. Acute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and nonesterified fatty acid (NEFA) concentrations during 300 min after a single administration of clenbuterol. Significantly higher serum insulin and NEFA concentrations (19.90±2.50 U/ml, p<0.01, and 0.69±0.04 mmol/L, p<0.001, respectively) were measured 30 min after the preprandial administration of clenbuterol in female pigs. Over the same period, the levels of blood glucose (4.42±0.30 mmol/L) showed no difference from those of control pigs. The postprandial serum NEFA concentration decreased moderately during 210 min after feeding. Postprandial blood glucose and insulin concentrations increased and reached maximal levels 120 min after clenbuterol administration (10.91±0.60 mmol/L and 85.22±7.24 U/ml, respectively), and returned to basal levels at 300 min (4.20±0.21 mmol/L and 7.75±1.60 U/ml, respectively) after the administration of clenbuterol. Subacute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and NEFA concentrations for 21 days after the repeated doses of clenbuterol. In addition, the influence of clenbuterol administration on the endocrine regulation of the onset of the next expected oestrus in female pigs was assessed by measuring their serum 17-oestradiol and progesterone concentrations. Blood glucose, serum insulin and NEFA concentrations after the last administration of clenbuterol did not differ significantly from those in control animals. The onset of the next expected oestrus occurred regularly without any significant difference in serum 17-oestradiol or progesterone concentrations between the treated (9.83±2.60 pg/ml and 0.15±0.03 ng/ml) and control pigs (8.52±2.70 pg/ml and 0.25±0.06 ng/ml). The study results suggest the duration of intravenous administration of clenbuterol in a growth-promoting dose necessary to influence the metabolic and endocrine activities in female pigs.     

Antagonistic effect of atipamezole on xylazine-induced sedation, bradycardia, and ruminal atony in calves.

Three doses of an alpha 2-adrenoreceptor antagonist, atipamezole, were administered to reverse xylazine-induced sedation, bradycardia, and ruminal atony in calves. Once a week for 4 weeks, each of 6 calves was administered IV 1 treatment of: 0.3 mg of xylazine/kg of body weight, followed in 10 minutes by 1 ml of 0.9% NaCl; 0.3 mg of xylazine/kg, followed in 10 minutes by 3 micrograms of atipamezole/kg; 0.3 mg of xylazine/kg, followed in 10 minutes by 10 micrograms of atipamezole/kg; or 0.3 mg of xylazine/kg, followed in 10 minutes by 30 micrograms of atipamezole/kg. The order of the 4 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 33.6 +/- 7.1 minutes (mean +/- SEM). Atipamezole administered at dosages of 3, 10, and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 20.5 +/- 3.0, 10.2 +/- 0.2, and 9.3 +/- 0.5 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Atipamezole given at 3, 10, and 30 micrograms/kg shortened the time from onset of lateral recumbency to standing to 40.2 +/- 6.9, 12.8 +/- 1.1, and 10.0 +/- 0.7 minutes, respectively. Drowsiness was found in calves given the lowest dosage of atipamezole (3 micrograms/kg) after the calves stood. Atipamezole given at dosages of 10 and 30 micrograms/kg reversed xylazine-induced ruminal atony in a dose-dependent manner. In addition, 30 micrograms of atipamezole/kg reversed xylazine-induced bradycardia, but the lower dosages of this antagonist did not. Results indicated that 30 micrograms of atipamezole/kg should be a useful antidote for xylazine overdose in cattle.     

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets

OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.     

Comparison of yohimbine, 4-aminopyridine and doxapram antagonism of xylazine sedation in deer (Cervus elaphus)

Trials were conducted to test the ability of yohimbine, 4-aminopyridine and doxapram given by intravenous injection to antagonise xylazine sedation in red deer (Cervus elaphus). Yohimbine produced the best and most consistent result. The mean time taken for 34 animals to stand spontaneously after receiving yohimbine (0.2 to 0.25 mg/kg) was 2 minutes 25 seconds and this occurred, on average, 33 minutes after the initial doze of xylazine. Control deer took 67 and 104 minutes on average to stand after receiving intravenous (0.64-0.96 mg/kg) and intramuscular (1.0-1.5 mg/kg) injections of xylazine respectively. Two deer which received an overdose of xylazine (4 mg/kg) recovered 3 and 9 minutes respectively after receiving yohimbine. Two deer given a high intravenous dose of yohimbine (1.0 mg/kg) became mildly nervous and anxious, but returned to normal within an hour. 4-aminopyridine (0.3 mg/kg) alone produced some arousal from xylazine sedation (0.6-1.0 mg/kg) but was inconsistent. In combination with yohimbine (0.125 mg/kg) it produced rapid recovery in two deer but caused convulsions in two other deer. Doxapram (1 mg/kg) produced respiratory stimulation and some arousal from xylazine sedation (0.6-1.0 mg/kg) in the majority of deer but the effect was transitory. Animals relapsed into moderate sedation and recumbency within 10 minutes and required vigorous stimulation to arouse them again. Yohimbine, administered by intravenous injection at a dose rate of 0.2 to 0.25 mg/kg, appears to be a safe and reliable drug for the reversal of xylazine sedation in deer.     

Antagonism of xylazine sedation with yohimbine, 4-aminopyridine, and doxapram in dogs

Groups of atropinized dogs (6 dogs/group) were sedated with xylazine (2.2 mg/kg of body weight, IM). At recumbency, the dogs were given IV saline solution (control groups), yohimbine (0.05, 0.1, and 0.2 mg/kg), 4-aminopyridine (4-AP; 0.3, 0.6, and 0.9 mg/kg), doxapram (0.5, 1.0, 2.0, and 4.0 mg/kg), or the smallest dose of these antagonists in dual combinations or in triple combination. Two additional groups were sedated with an overdose of xylazine (11 mg/kg, IM). At recumbency, 1 of these groups was given saline solution IV and the other group was given yohimbine IV (0.4 mg/kg) as the antagonist. With the 2.2 mg/kg dose of xylazine, control mean arousal time (MAT) and mean walk time (MWT) were 15.5 minutes and 24.8 minutes, respectively. These values were decreased by the individual antagonists to 0.5 to 2.5 minutes and 0.9 to 7.4 minutes, respectively. Approximate equipotent doses of antagonists (mg/kg) were: yohimbine, 0.2; 4-AP, 0.6; and doxapram, 0.5. Relapses did not occur after yohimbine or 4-AP. With doxapram, muscle tremors and spasms, abnormal postures, or aggressive behavior occurred in several dogs and several dogs had partial or complete relapses. The small doses of individual antagonists were synergistic with regard to MAT, MWT, and duration of residual sedation, but the various combinations of antagonists were not more effective in these regards than were larger doses of the single antagonists. With the overdose of xylazine, control MAT and MWT were 41.5 minutes and 144.5 minutes, respectively. Yohimbine decreased these values to 2.2 minutes and 2.5 minutes, respectively. Relapses did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonistic effect of idazoxan on xylazine-induced central nervous system depression and bradycardia in calves

Two doses of an alpha 2-adrenoreceptor antagonist, idazoxan, were administered to reverse the CNS depressant and bradycardia effects of xylazine in calves. Once a week for 3 weeks, each of 6 calves were administered IV one treatment of: (1) 0.2 mg of xylazine/kg of body weight followed in 10 minutes by 1 ml of 0.9% NaCl, (2) 0.2 mg of xylazine/kg followed in 10 minutes by 10 micrograms of idazoxan/kg, or (3) 0.2 mg of xylazine/kg followed in 10 minutes by 30 micrograms of idazoxan/kg. The order of the 3 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 27.2 +/- 3.0 minutes (mean +/- SEM). Idazoxan administered at dosages of 10 and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 11.5 +/- 0.8 and 10.3 +/- 0.2 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Idazoxan given at dosages of 10 and 30 micrograms/kg shortened the time to standing to 16.8 +/- 1.7 and 11.3 +/- 0.2 minutes, respectively. Idazoxan given at a dosage of 30 micrograms/kg also reversed xylazine-induced bradycardia. Results indicated that idazoxan should be a useful antidote for xylazine overdose in cattle.     

Antagonism of xylazine sedation by 4-aminopyridine and yohimbine in cattle

Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0.2 to 0.3 mg/kg of body weight). When the steers were maximally sedated, group I (control group) were given isotonic saline solution (1 ml, IV), group II were given 4-aminopyridine (4-AP, 0.3 mg/kg) IV, group III were given yohimbine hydrochloride (0.125 mg/kg) IV, and group IV were given 4-AP (0.3 mg/kg) plus yohimbine hydrochloride (0.125 mg/kg) IV. The 4-AP decreased mean standing time (MST; time until animal could stand unaided) from 94.3 minutes (control) to 13.4 minutes. Yohimbine decreased MST to 27 minutes. The combination of 4-AP + yohimbine decreased MST to 7.4 minutes. Mean total recovery time (MTRT; time from xylazine injection until normal behavior, including eating and drinking) was not significantly (P = greater than 0.05) decreased from control values by any of the antagonists tested. The combination of 4-AP + yohimbine decreased MST in animals given a 3X overdose of xylazine (0.6 mg/kg) from 124 minutes (control) to 30.3 min. The MTRT was not significantly (P greater than 0.05) decreased from control values. Two animals given a 5X overdose of xylazine (1 mg/kg) and then given 4-AP + yohimbine had a MST of 32.5 minutes and a MTRT of 3.7 hours. The combination of 4-AP + yohimbine produced marked antagonism of xylazine sedation in cattle. The combination of antagonists may prove to be useful for the arousal of animals sedated with xylazine alone or with a combination of sedatives including xylazine.