The anti-nociceptive and cardiopulmonary effects of extradural fentanyl–xylazine in sheep

Objective To compare the anti‐nociceptive effects of extradural xylazine, fentanyl and a xylazine–fentanyl combination in sheep, and to measure the cardiopulmonary effects of the xylazine–fentanyl combination. Study design Prospective, randomized study. Animals Twenty‐five half‐merino ewes 2–4 years of age and body mass 54.2 ± 1.1 kg. Methods Six sheep in group 1 received 0.2 mg kg^?1 xylazine by extradural injection, six in group 2 received fentanyl 1.5 µg kg^?1 and 13 in group 3 received the combination of both treatments. In all groups, drugs were mixed with saline (0.15 mL kg^?1 before injection). Pulmonary and carotid arterial catheters were placed in seven sheep of group 3 which were used to evaluate cardiopulmonary effects. Anti‐nociception was determined by the response to electrical stimulation (40 V for 1.5 milliseconds) of the left flank and by superficial and deep muscular ‘pinpricking’ stimulation of the pelvic and thoracic limbs and thoracolumbar region. Results Lack of response to electrical stimulation at the left flank was present in 10 ± 1.1 minutes (mean ± SEM) (group 1) and in 4.5 ± 0.5 minutes in group 3. The duration of lack of response to electrical stimulation at the left flank was 96 ± 6 minutes in group 1 and 315 ± 6 minutes in group 3. Responses persisted in group 3. Significant decreases (p < 0.05) in cardiac output 30, 45, 60 and 90 minutes after injection, and in cardiac work at 30 and 45 minutes were observed in the seven animals of group 3. Arterial blood pH was lowest at 90 minutes, arterial bicarbonate was lowest at 60 minutes and values for both arterial and mixed venous base excess increased significantly at 60 and 90 minutes. There was no significant change from baseline values in heart rate, mean arterial blood pressure, respiratory rate, body temperature, systemic vascular resistance, arterial and mixed venous PO₂, PCO₂, oxygen saturation, blood oxygen content, haemoglobin concentration, mixed venous blood bicarbonate and pH. Conclusions Fentanyl decreases the onset time and prolongs the duration of anti‐nociception produced by xylazine. The combination decreases cardiac output but is without significant respiratory effects. Clinical relevance Further studies are required to show that surgery is possible in sheep after extradural xylazine–fentanyl injection.     

Sedative effects of intramuscular administration of a low dose of romifidine in dogs

OBJECTIVE: To evaluate sedative effects of IM administration of a low dose of romifidine in dogs. ANIMALS: 13 healthy adult Beagles. PROCEDURE: Physiologic saline solution (0.2 ml), 0.1 % romifidine (10, 20, or 40 microg/kg), or 10% xylazine (1 mg/kg) was given IM in a crossover study design. Heart rate, respiratory rate, rectal temperature, hemoglobin saturation, and scores for sedation, muscle relaxation, posture, auditory response, and positioning response were recorded before and at regular intervals for up to 240 minutes after drug administration. RESULTS: Scores for sedation, muscle relaxation, posture, auditory response, and positioning response increased in a dose-dependent manner after romifidine administration. Sedation induced by the highest dose of romifidine (40 microg/kg) was comparable to that induced by xylazine (1 mg/kg). Heart rate, respiratory rate, and rectal temperature decreased in a dose-dependent manner after romifidine administration, but hemoglobin saturation did not change. CONCLUSIONS AND CLINICAL IMPLICATIONS: Romifidine (10, 20, or 40 microg/kg, IM) is an effective sedative in dogs, but causes a decrease in heart rate, respiratory rate, and rectal temperature.     

Evaluation of the arrhythmogenicity of a low dose of acepromazine: comparison with xylazine.

Alteration in the arrhythmogenic dose of epinephrine (ADE) was determined in 6 healthy dogs under halothane anesthesia following the administration of xylazine at 1.1 mg/kg i.v. and acepromazine at 0.025 mg/kg i.v. The order of treatment was randomly assigned with each dog receiving both treatments and testing was carried out on 2 separate occasions with at least a 1 wk interval. The ADE determinations were made prior to drug administration during halothane anesthesia (CNTL) and then 20 min and 4 h following drug treatment. Epinephrine was infused for 3 min at increasing dose rates (2.5, 5.0, 10.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached within the 3 min of infusion or the 1 min following cessation. The interinfusion interval was 20 min. There was a significant difference (P = 0.0001) in the ADE determined following acepromazine administration at 20 min (20.95 micrograms/kg +/- 2.28 SEM) compared to CNTL (6.64 micrograms/kg +/- 1.09), xylazine at 20 min (5.82 micrograms/kg +/- 0.95) and 4 h (6.13 micrograms/kg +/- 1.05), and acepromazine at 4 h (7.32 micrograms/kg +/- 0.34). No other significant differences existed (P < 0.05). In this study we were unable to show any sensitization to epinephrine following xylazine administration during halothane anesthesia, while a protective effect was shown with a low dose of acepromazine.     

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.     

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.     

Safety and efficacy of intramuscular propofol administration in rats

ObjectiveTo determine the safety and efficacy of intramuscularly (IM) injected 100% propofol and propofol–dimethyl sulfoxide (DMSO) mixtures.Study designBlinded, controlled study.AnimalsTwenty-five Sprague–Dawley adult female rats weighing 307 ± 4 g.MethodsThree different study protocols were used. In the first set of experiments, rats were injected with 100% propofol (2,6-diisopropylphenol) ranging from 0 to 490 mg kg⁻¹ into one biceps femoris and equivolume 0.9% saline controls were injected into the contralateral limb. In the second set of experiments, rats were injected with 0 or 262 mg kg⁻¹ propofol that was dissolved in 10–40% DMSO (by weight); 0.9% saline was used for contralateral limb control injections. In the third experiment protocol, one rat received 293 mg kg⁻¹ propofol intraperitoneally (IP) to verify potency of the pure compound. Rats were evaluated every 2 minutes for signs of sedation and anesthesia. After 24 hours, all rats were killed, and tissue samples from saline and propofol injection sites were evaluated by veterinary histopathologists who were blinded to drug treatment (propofol versus control) and dose.ResultsMost rats did not exhibit substantial sedation with IM propofol, and no rat became anesthetized even when propofol was administered in excess of the lethal IP dose. Histology of injection sites demonstrated significant tissue inflammation and necrosis associated with propofol injections, but not with saline injections.Conclusions and clinical relevanceOne hundred percent propofol is neither safe nor effective when administered via the IM route; presumably as a result of poor systemic uptake of the hydrophobic drug. Newer, water-soluble propofol formulations may circumvent these pharmacokinetic problems, yet local tissue injury might still be possible if high concentrations of free propofol drug are liberated.     

The efficacy of a subcutaneous injection of soluble Vitamin B12 in lambs

AIMS: To assess the efficacy of a soluble Vitamin B12 injection in lambs by measuring changes in the serum and liver Vitamin B12 concentrations. METHODS: Thirty-six lambs were injected subcutaneously with 2 mg of soluble Vitamin B12 while another group of 36 served as untreated controls. Blood and liver biopsy samples for Vitamin B12 determinations were collected just before the injection and at days 1, 2, 5, 8, 16, 24, 30 and 45. RESULTS: The serum Vitamin B12 concentrations of the Vitamin B12 treated lambs increased rapidly compared to the untreated lambs. Concentrations peaked at day 2, decreased rapidly to day 8, and then decreased more slowly until day 24 when there were no longer differences between the groups. Liver Vitamin B12 concentrations of the Vitamin B12 treated lambs were significantly greater over days 8-24. CONCLUSION: A subcutaneous injection of 2 mg of soluble Vitamin B12 was effective in increasing and maintaining the Vitamin B12 status of lambs for about 24 days. CLINICAL SIGNIFICANCE: This Vitamin B12 product is only effective for preventing cobalt deficiency in lambs for about 4 weeks.     

The anthelmintic efficacy of five plant products against gastrointestinal trichostrongylids in artificially infected lambs

Forty-eight helminth-free lambs were divided into eight groups (A-H) of six animals. Groups A-G were infected artificially with 10,000 third stage larvae of Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus colubriformis, whereas group H remained uninfected. Thirty days post-infection the lambs were treated orally with a single dosage of one of the following products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract (70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L. (Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd. (Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183 mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of the seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW of pyrantel tartrate and group G with 50% ethanol. Group H remained untreated. Only the ethanol extract of F. parviflora caused a strong reduction of the faecal egg counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus and T. colubriformis on day 13 post-treatment. The extract was as effective as the reference compound pyrantel tartrate. Therefore, the ethanol extract itself or single constituents of F. parviflora could be a promising alternative source of anthelmintic for the treatment of gastrointestinal trichostrongylids in small ruminants.     

Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses.

The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration (MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/kg/min at which at least 4 premature ventricular depolarizations occurred in a 15-second period. Xylazine (1.1 mg/kg, IV) was administered after the control ADE was determined. Xylazine did not significantly alter the ADE (control, 1.12 +/- 0.38 micrograms/kg/min; xylazine, 1.21 +/- 0.46 micrograms/kg/min). Blood pressure increased transiently for 8 minutes after xylazine administration. Baseline systolic and diastolic arterial pressures and heart rate were not significantly different from control baseline pressures and heart rate 15 minutes after xylazine administration. Blood pressure and heart rate increased significantly during control and xylazine ADE determinations. Significant differences in pH, PaO2, PaCO2, or base excess were not observed between baseline and ADE in the control or xylazine groups. One horse developed atrial fibrillation, and 2 horses developed ventricular fibrillation during ADE determinations.     

The efficacy of an albendazole intraruminal controlled-release device against gastrointestinal parasitism in lambs.

The effectiveness of albendazole in a controlled-release bolus in controlling gastrointestinal nematodes in lambs was assessed during the summer of 1986. Faecal egg counts were almost entirely negative throughout in the treated group and larval challenge remained low at below 2000 larvae kg-1. Untreated control lambs showed a characteristic pattern of auto-infection, culminating in a peak pasture larval count of over 70,000 larvae kg-1 and an outbreak of parasitic gastroenteritis in September associated with a serum pepsinogen concentration of 1.183 IU tyrosine and a mean worm burden of 91,165 nematodes at necropsy, including Ostertagia, Trichostrongylus and Nematodirus species. Subject to the restrictions imposed by the size of the bolus, this was considered to be a highly effective method of seasonal parasite control.     

Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril

The prophylactic efficacy of a single oral dose of toltrazuril against coccidiosis (mixed Eimeria infections) in naturally infected lambs was evaluated in two experiments. Toltrazuril at 20 mg kg-1, given on Day 7 or Day 10 after turnout on pasture, proved to be highly efficacious in preventing clinical coccidiosis under Norwegian conditions. Toltrazuril reduced the oocyst output to very low levels, prevented the development of diarrhoea and improved weight gain during the first 4-5 weeks after treatment. Treatment on Day 7 was superior to treatment on Day 10 with respect to improving weight gain and preventing the development of soft faeces. Lambs treated with toltrazuril on Day 7 seemed to be as immune as untreated lambs to natural reinfections with coccidia later in the grazing season. In one of the experiments, natural infections with the nematode Nematodirus battus produced a coccidiosis-like disease in some lambs simultaneously with the outbreak of coccidiosis.     

Comparative analgesia of xylazine, xylazine/morphine, xylazine/butorphanol, and xylazine/nalbuphine in the horse, using dental dolorimetry

Xylazine, morphine, butorphanol, and nalbuphine were evaluated in 5 adult male horses, using dental dolorimetry. Comparisons were made at 30, 60, and 100 minutes after IV drug administration. Peak analgesia and the time to develop peak analgesia also were compared. Xylazine induced a marked increase in the tooth pulp pain threshold measurements as did the xylazine/narcotic combinations. Statistical differences were not detectable between these treatments. Xylazine and xylazine/butorphanol were better analgesics than was butorphanol alone at 30 and 60 minutes. Xylazine resulted in peak analgesia faster than did butorphanol or the combination of xylazine/butorphanol. Additive analgesic effects were not detected with the combined treatments.     

The effect of antibody to caseous lymphadenitis in ewes on the efficacy of vaccination in lambs

The effect of maternal antibody to the toxin of Corynebacterium pseudotuberculosis, produced by caseous lymphadenitis (CLA) in ewes or by vaccinating ewes before lambing, on the efficacy of vaccination against CLA in their lambs was examined. Lambs were allocated to treatments according to either the vaccination history of their dam or level of CLA toxin antibody of their dam. They were vaccinated twice using 2 different inoculation regimes and then artificially infected with CLA organisms. The number of lambs with CLA lesions was assessed at slaughter. In one experiment high levels of CLA toxin antibody activity in ewes were associated with decreased efficacy of CLA vaccination in their lambs, when lambs were vaccinated at 2 and 8 weeks or 8 and 14 weeks of age. In a second experiment the efficacy of lamb vaccination at 8 and 12 weeks, but not at 14 and 18 weeks of age, was decreased. In sheep flocks with a high prevalence of CLA, vaccinating lambs against CLA at less than 10 weeks of age may not produce optimum protection against CLA in lambs. There was no difference in infection rate between lambs from vaccinated and unvaccinated ewes. However, vaccination of lambs at 2 and 8 wks was less effective that vaccination at 8 and 14 weeks, probably due to reduced immunocompetence in young lambs. In sheep flocks where significant numbers of lambs receive their primary vaccination at less than 3 weeks of age vaccination programmes to control CLA in lambs may be less effective.     

苏尼特羔羊肌内脂肪沉积规律及其与肌肉嫩度相关性的研究

本试验以苏尼特羊为研究对象,采用单因子试验设计,对不同屠宰体重(10、20、30kg和40kg)羔羊的日增重、屠宰率和肉质进行系统研究。试验结果表明:苏尼特羔羊的体重对日增重、屠宰率、肌肉水分含量、肌内脂肪含量、剪切力和系水率都有显著影响(P0.05);肌内脂肪含量与肌肉剪切力呈极显著负相关(r=-0.983,P0.01)。     

Alteration in the arrhythmogenic dose of epinephrine (ADE) following xylazine administration to halothane-anesthetized dogs

The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 microgram/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15-sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 +/- 0.522 to 4.17 +/- 0.679 micrograms/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 +/- 4 to 99 +/- 4.9 b.p.m.), and mean arterial pressure significantly increased (83 +/- 4.0 to 122 +/- 3.4 mm Hg). Heart rate measured immediately prior to epinephrine-induced arrhythmia formation was significantly increased following xylazine administration (177 +/- 8 vs 78 +/- 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed alpha agonist, potentiated halothane-induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinephrine infusions.     

The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high‐performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio‐respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Cl_area, Vd_area and T_1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Cl_area/F, Vd_area/F and T_1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.