Xylazine and a xylazine/fentanyl citrate/azaperone combination in farmed deer. II: velvet antler removal and reversal combinations

Three studies were undertaken on farmed red and red x wapiti deer to evaluate xylazine and a xylazine/fentanyl citrate/azaperone combination for velvet antler removal. In the first experiment, 30 1-2 year-old red and 25% red x wapiti deer whose velvet was to be removed were given either 5% xylazine alone at 0.5 mg/kg body weight intramuscularly or the same dose rate of a commercially available mixture of 5% xylazine with the addition of 0.4 mg of fentanyl citrate and 3.2 mg of azaperone per ml. Physiological, behavioural and analgesic responses and reversal times after yohimbine or yohimbine and naloxone were monitored. There were no differences in heart rate, respiration rate, sedative or analgesic properties detected between xylazine or the xylazine/fentanyl citrate/azaperone combination. All deer became recumbent, but those given the xylazine/fentanyl citrate/azaperone combination became recumbent more rapidly than those given xylazine alone (9.4 and 12.5 minutes, respectively, p<0.05). The arousal pattern and timing of reversal of xylazine and xylazine/fentanyl citrate/azaperone using yohimbine and yohimbine and naloxone, respectively, were similar. The second experiment evaluated the reversal of the xylazine/fentanyl citrate/azaperone combination with either yohimbine or yohimbine and naloxone in 43 3-year-old red deer stags after velvet antler removal. There were no differences in arousal pattern or time to standing between reversal treatments. Sixteen 1-year-old red and 25% red x wapiti stags were used in the third experiment to evaluate clinically the analgesic properties of xylazine and xylazine/fentanyl citrate/azaperone combination during velvet removal without the application of a local anaesthetic agent. Withdrawal responses were observed in most deer after the xylazine/fentanyl citrate/azaperone combination at dosages containing 0.5, 0.7 and 0.75 mg of xylazine/kg and after xylazine alone at 0.7 mg/kg, indicating that insufficient analgesia was provided by the systemic agent for the surgical procedure of velvet antler removal. These studies have shown that the knock-down effect of the xylazine/fentanyl citrate/azaperone combination was more rapid than that of xylazine alone, but that other physiological, behavioural and analgesic responses at doses used and evaluated by the methods used were similar. Reversal of both the xylazine and xylazine/fentanyl citrate/azaperone combination was similar when using either yohimbine alone for xylazine and the xylazine/fentanyl citrate/azaperone combination or yohimbine and naloxone for the xylazine/fentanyl citrate/azaperone combination. The evaluation of surgical analgesia for antler removal suggested that both xylazine alone and the xylazine/fentanyl citrate/azaperone combination provided insufficient analgesia and that local anaesthetic should be used in all cases.     

Xylazine and a xylazine/fentanyl citrate/azaperone combination in farmed deer. I: dose rate comparison

Six 1-year-old farmed red deer were used to compare physiological and behavioural responses to a range of doses of 5% xylazine with or without the addition of 0.4 mg of fentanyl citrate and 3.2 mg of azaperone per ml. Each deer was randomly assigned to one of six treatments: xylazine alone at 0.4 and 0.6 mg/kg, the xylazinelfentanyl citrate/azaperone combination containing 0.2, 0.4 and 0.6 mg/kg of xylazine, or a sterile water control. Injections were given intramuscularly in the anterior neck, operator blind, on each of 6 sampling days between October and January, such that each deer received all treatments with 9-28 days between each treatment. Measurements included heart rate and respiration rate. A 0-3 scoring system (normal to nil response, respectively) was devised to record sedative responses (body stance, head position, degree of eye closure, palpebral reflex, resistance to movement of the head, response to noise) and analgesic responses to touch and pinching of the ear, and response to a needle prick in the gluteal region. Scores were added to produce a sedation score and analgesia score, respectively, for each treatment. Records were taken immediately prior to injection and thereafter at 5, 14, 25, 35, 60, 90, 120, 150, 180, 210, 240 and 300 minutes. All deer given each dose rate of the xylazine and the xylazine/fentanyl citrate/azaperone combination became recumbent. There was a tendency for the time to recumbency and variation of time to recumbency to be shorter at higher dose rates and with the addition of fentanyl citrate and azaperone to xylazine, particularly with xylazine at 0.4 mg/kg. These trends were not statistically significant (p>0.05). The duration of recumbency was shorter with the low dose of the xylazine/fentanyl trateiazaperone combination (0.2 mg/kg of xylazine) than for the higher doses of xylazine alone or the combination of drugs (p<0.05). There were no significant differences in heart rates or respiration rates between treatments, although all treatments significantly reduced both heart and respiration rates (p<0.01). The sedation scores showed similar peak responses and timing to peak responses (14-25 min) to both drug treatments and all dose rates, but the responses were less persistent for lower doses. The analgesia scores showed a similar pattern, with peak responses 14-35 minutes after administration and more persistence at higher dose rates of both xylazine alone and the xylazine/fentanyl citrate/azaperone combination. This study has shown that most physiological and behavioural responses to a range of doses of xylazine or the xylazine/fentanyl citrate/azaperone combination were statistically similar. However, there was a tendency for recumbency to occur more rapidly and with less variation in timing when the mid-range dose of the drug combination was used, supporting the observation by practitioners that the drug combination results in a more rapid and reliable state of recumbency at a lower dose rate of xylazine.     

Possible role of plasma neurotensin in regulating the excitatory neural control of the rectum of the fowl

Effects of neurotensin (NT) applied via the blood vessel on the responses to stimulation of Remak's nerve (RNS) were investigated in the chicken isolated and perfused rectums. NT (5 ng-2 micrograms/ml) produced a concentration-dependent inhibition of the constituent contraction but not relaxation of the responses to RNS. In addition, high concentrations of NT (over 80 ng/ml) produced a contraction of the rectal muscle. Propranolol, a beta-adrenoceptor blocking agent, and guanethidine, an adrenergic neurone blocking agent, were able to reduce the inhibitory effect of NT on the response to RNS while potentiating the contractile effect of NT on the rectal muscle. NT (0.1 and 1 microgram/ml), like norepinephrine, decreased the flow rate of perfusate from the isolated rectum which was perfused at a constant pressure. Guanethidine enhanced norepinephrine-induced vasoconstriction, and phentolamine, an alpha-adrenoceptor blocking agent, plus propranolol was able to abolish it. Either of these prior applications resulted in a small but significant reduction of NT-induced vasoconstriction. These findings suggest that NT in plasma may function as a circulating hormone to exhibit an inhibitory action on the excitatory neural input to the rectum in the chicken, and that catecholamine release from adrenergic nerve terminals by NT may account for some but not all of the activity.     

Effect of hyperlipidemia on cardiovascular responses to adrenergic stimulation in piglets.

This study was designed to assess the effect of hyperlipidemia on cardiovascular responses to adrenergic stimulation in a porcine model. Four-week-old piglets (n = 10) were divided into two groups; one fed a control diet and the other was fed an atherogenic diet for 8 weeks. Cardiovascular responses were evaluated to both norepinephrine (NE; 0.5 and 2.5 micrograms/kg) and isoproterenol (ISO; 0.1 and 0.5 microgram/kg) from simultaneous recordings of femoral arterial pressure, heart rate, left intraventricular pressure and left intraventricular dP/dt. It was found that no significant difference in the baseline values of cardiovascular function was observed between the control and hyperlipidemic groups. However, in the hyperlipidemic group as compared with the control group: 1) arterial blood pressure responses to NE were significantly increased (P less than 0.05), 2) cardiac contractile responses to NE and ISO were significantly potentiated (P less than 0.05), and 3) reflex bradycardia in response to increasing arterial blood pressure did not occur. These findings indicate that hyperlipidemia can potentiate the cardiovascular responses to adrenergic stimulation, whereas reflex cardiovascular regulation is somewhat altered by hyperlipidemia. Conceivably, these observations may have relevance to the possible role of the mechanism of the interaction of hyperlipidemia and hypertension in atherogenesis.     

Anaesthetics for General Anaesthesia in Growing Pigs

A comparison was made between different anaesthetics for general anaesthesia in growing pigs, with focus on minor surgery under field conditions and for experiments in clinical research. Healthy crossbreed pigs (HampshirexYorkshirexSwedish Landrace) weighing 20–45 kg were used. The anaesthetics combinations compared were 1) azaperone plus metomidate (AM), 2) Zoletil® (zolazepam + tiletamine) plus xylazine (ZX), and 3) Zoletil® plus xylazine plus ketamine (ZXK). Parameters measured were: heart rate, respiratory rate, blood pressure, body temperature, and depth of analgesia (pin-prick). Minor surgery was performed to test the reliability of the “pin-prick” tests.It was clearly shown that AM produces anaesthesia with good cardiovascular stability and is a drug combination that is suitable for minor surgery. ZX also produces a good anaesthesia characterized by reliable and rapid induction. Good cardiovascular function is maintained, and the laryngeal relaxation makes intubation possible. These characteristics are very useful in a laboratory environment, as easy handling to avoid stress is necessary for research. Although it is difficult to evaluate the quality of analgesia from this study, it is concluded that ZX did not provide a superior anasthesia and analgesia compared to AM in crossbreed pigs. However, these drugs are too expensive for regular use in ambulatory practice. The effects of ZXK resemble those of ZX, but the ZXK-drug combination has no anaesthetic advantages and is more laborious to work with. kw|Keywords|k]azaperone; k]metomidate; k]Zoletil®, xylazine; k]ketamine     

SYMPATHETIC AND PARASYMPATHETIC EFFECTS OF ACUPUNCTURE ON THE CARDIOVASCULAR SYSTEM OF DOGS UNDER HALOTHANE ANESTHESIA

Evidence of sympathetic or parasympathetic stimulation of the cardiovascular system has been obtained in dogs under halothane anesthesia following acupuncture. Acupuncture at Jen Chung (Go-26), which is located on the phithrum, results in sympathetic input and an increase in cardiac output, heart rate and mean arterial pressure. These effects can be inhibited by the beta adrenergic blocking agent, propranolol. Acupuncture at Tsu San Li (St-36), which is located distal to the lateral condyle of the tibia, results in parasympathetic input and decrease in cardiac output. This effect is inhibited by atropine.     

Anaesthetic complications in pigs undergoing MRI guided convection enhanced drug delivery to the brain: a case series

ObservationsA total of 13 intracerebral infusions were performed at approximately 1 month intervals in three NIH miniature pigs over the age range of 31–59 weeks. Pigs received azaperone and ketamine premedication to allow venous cannulation and propofol induction of anaesthesia. Anaesthesia was maintained with isoflurane throughout cranial surgery and MRI scanning. Physiological monitoring during surgery consisted of blood pressure, pulse, temperature and oxygen saturation monitoring, ECG and capnography. Analgesia consisted of meloxicam and morphine. However, during MRI scanning blood pressure and ECG monitoring had to be discontinued. Anaesthetized pigs underwent intermittent intraputamenal convection enhanced delivery (CED) of gadolinium with real-time magnetic resonance imaging. Progressive tachycardia was consistently observed in all pigs during CED with a mean ± SD maximum increase of 41 ± 22 beats minute^?1 from a baseline heart rate of 96 ± 9 minute^?1. The heart rate remained elevated until recovery. A mean reduction in body temperature of 2.8 ± 0.6 °C from the start of anaesthesia was also observed during the period of MRI scanning. All pigs recovered from anaesthesia smoothly and heart rates returned to normal during the recovery period.ConclusionsHypothermia is common in pigs undergoing this sedation and anaesthesia protocol. Convection enhanced delivery of drugs in healthy anaesthetized pigs may result in tachycardia.     

Comparison of azaperone–detomidine–butorphanol–ketamine and azaperone–tiletamine–zolazepam for anaesthesia in piglets

ObjectiveTo investigate a combination of azaperone, detomidine, butorphanol and ketamine (DBK) in pigs and to compare it with the combination of azaperone, tiletamine and zolazepam (TZ).Study designProspective, randomized, blinded, cross–over study.AnimalsTwelve clinically healthy crossbred pigs aged about 2 months and weighing 16–25 kg.MethodsPigs were pre–medicated with azaperone (4 mg kg^?1). Ten minutes later anaesthesia was induced with intramuscular DBK (detomidine 0.08 mg kg^?1, butorphanol 0.2 mg kg^?1, ketamine 10 mg kg^?1) or TZ (tiletamine and zolazepam 5 mg kg^?1). The pigs were positioned in dorsal recumbency. Heart and respiratory rates, posture, anaesthesia score, PaO₂, PaCO₂, pH and bicarbonate concentration were measured. t–test was used to compare the areas under time–anaesthesia index curve (AUC_anindex) between treatments. Data concerning heart and respiratory rates, PaO₂, PaCO₂ and anaesthesia score were analysed with anova for repeated measurements. Wilcoxon signed rank test was used for the data concerning the duration of sedation and anaesthesia.ResultsThe sedation, analgesia and anaesthesia lasted longer after DBK than TZ. The AUC_anscore were 863 ± 423 and 452 ± 274 for DBK and TZ, respectively (p = 0.002). The duration of surgical anaesthesia lasted a median of 35 minutes (0–105 minutes) after DBK and a median of 15 minutes (0–35 minutes) after TZ (p = 0.05). Four pigs after DBK and six after TZ did not achieve the plane of surgical anaesthesia. The heart rate was lower after DBK than after TZ. Both treatments had similar effects on the other parameters measured.ConclusionsAt the doses used DBK was more effective than TZ for anaesthesia in pigs under field conditions.Clinical relevanceThe combinations can be used for sedation and minor field surgery in pigs. The doses and drugs chosen were insufficient to produce a reliable surgical plane of anaesthesia in these young pigs.     

Cardiopulmonary effects of the combination of neuroleptic azaperone and hypnotic metomidate in swine.

Cardiopulmonary measurements were made at given intervals up to 120 minutes on 6 awake, unanesthetized pigs given azaperone and metomidate. Decreases from control values occurred in arterial blood pressure (deltaBPart = 30 mm of Hg), heart rate (deltaHR = 30 to 35 beats/minute), and cardiac index (deltaCI = 1.5 L/minute/m2). Blood gas and pH measurements indicated no severe impairment of pulmonary function or arterial acidosis. Although the drugs led to decreases in the various functions, cardiopulmonary function remained stable and uncompromised.     

Residues of azaperone and azaperol in slaughter pigs

An investigation was carried out to determine the residues of azaperone in slaughter pigs and pig meat products. The butyrophenone tranquillizer azaperone is frequently administered to pigs by intramuscular injection in order to reduce mortality and loss of meat quality resulting from transportation from the farm to the slaughter house. In the pig, following administration of azaperone as recommended by the manufacturer (0.4 mg/kg i.m.) residue concentrations of about 0.05 μg/g azaperone, and 0.20 μg/g azaperol (the main biotransformation product in the pig) were found in the kidneys; the kidneys proving to be the sampling organs of choice. Pasteurization and other technological procedures did not influence residues measurably. Toxicological evaluation suggests that the residues found do not per se constitute a danger to public health. None the less, the presence of any drug residue in meat or meat products is undesirable, and alternative, non-pharmacological approaches to the problems arising from transportation prior to slaughter should be considered.     

Comparison of two combinations of sedatives before anaesthetising pigs with halothane and nitrous oxide

Two groups of 21 three-month-old Landrace x Large White pigs were sedated with either azaperone (2 mg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) (group A), or detomidine (100 microg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) (group D) administered intramuscularly, before being anaesthetised with halothane, oxygen and nitrous oxide for a bilateral stifle arthrotomy. The pigs' heart rate, respiratory rate, mean arterial blood pressure, electrocardiogram, arterial oxygen saturation, arterial blood gases, and oesophageal and rectal temperature were measured while they were anaesthetised and five minutes after they were disconnected, and their recovery times and any complications were recorded. Both groups were well sedated. Their heart rate was unchanged during the period of anaesthesia but increased when they recovered. The respiratory rate, mean arterial blood pressure and rectal temperature were lower in group A than in group D (P<0.05). Mild respiratory acidosis developed during anaesthesia in both groups. Both groups recovered equally rapidly and complications were generally minor, though two pigs in group D appeared to develop malignant hyperthermia.     

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Neuromuscular blocking agents should be included as part of a balanced anaesthetic protocol to improve anaesthetic management, although doses are not always established for each species. Cis‐atracurium is a benzylisoquinolinium neuromuscular blocking agent with an intermediate duration of action devoid of significant adverse effects previously used in pigs with a wide dosage range. Cis‐atracurium was administered at 1 mg/kg bolus to sixteen pigs to establish its time profile and effects. The pigs were premedicated intramuscularly with 4 mg/kg azaperone, 8 mg/kg ketamine and 0.2 mg/kg morphine IM and maintained with isoflurane in oxygen. After cis‐atracurium administration, neuromuscular monitoring via acceleromyography was started until the recovery of the 90% of the train of four ratio. Complete decrease in the train of four ratio was accomplished in eleven pigs. Onset of action was 70 s, with a recovery of the fourth twitch at 26 min and a recovery of a train of four ratio greater than 90% in 60 min. In conclusion, 1 mg/kg intravenous cis‐atracurium in the pig allowed for a rapid onset of action and a complete recovery after 60 min although high variability in the time profile is seen.     

The effect of azaperone on the agonistic behaviour of boars: a pilot study

Previously unacquainted adult boars are often penned together and transported over long distances. This study examined the effect of azaperone, a drug used to reduce fighting in young pigs, on the behaviour of adult boars in close confinement.     

Sudden death in the presence of overt β‐adrenergic receptor activation in guinea pigs immediately following isoflurane anesthesia

Observations A case series of sudden death is reported in five consecutive guinea pigs following anesthesia with inhalational isoflurane during β‐adrenergic receptor stimulation with isoproterenol. Sustained‐release isoproterenol pellets or mini‐osmotic pumps were implanted subcutaneously in male Dunkin–Hartley guinea pigs as part of a research study to assess the interplay of adrenergic receptor activation and the development of atrial arrhythmias. The continuous exposure to isoproterenol resulted in a similar presentation and eventual sudden death in all guinea pigs exposed to inhalational isoflurane between 15 to 40 minutes after discontinuation of anesthesia. Death occurred in guinea pigs in this case series despite the fact that doses of isoproterenol used were more than 10‐fold lower than previously reported in guinea pigs in the absence of isoflurane anesthesia. The cause of death was suspected to be due to an interaction of isoproterenol with isoflurane anesthesia, as placebo implantation or anesthesia alone did not result in cardiac arrest. Of four subsequent guinea pigs anesthetized with the combination of xylazine and ketamine (X/K), three survived isoproterenol implantation for the full 21‐day study period while one died perioperatively. Conclusions There was an increased rate of post‐anesthetic mortality associated with isoproterenol pellet implantation in guinea pigs anesthetized with isoflurane compared to X/K. This may be due to the detrimental effects of the combination of isoflurane during overt β‐adrenergic receptor activation or cardioprotective effects of X/K anesthesia during β‐adrenergic receptor hyperactivity.     

Prediction of motor responses to surgical stimuli during bilateral orchiectomy of pigs using nociceptive flexion reflexes and the bispectral index derived from the electroencephalogram

Movement responses to noxious stimuli during anaesthesia indicate nociception. Under experimental conditions consistent prediction of such movement responses has been achieved by the use of nociceptive flexion reflexes (NFRs). The aim of this study was to investigate the reliability of NFRs and the electroencephalogram bispectral index (BIS) in predicting motor responses to real surgical stimuli in pigs. The study was undertaken in 30 pigs undergoing bilateral orchiectomy under ketamine/azaperone anaesthesia. During the operation, movement responses to seven distinct surgical steps that provided noxious stimuli of different intensity were evaluated. Any movement response of limbs or the head was considered as a positive response. For each surgical step the values of NFRs and the BIS obtained just prior to the step were tested as predictors of movement responses.The prediction probability for movement responses was 0.58 ± 0.04 for the BIS and 0.76 ± 0.03 for the NFRs. It was concluded that NFRs but not the BIS can predict the effectiveness of ketamine anaesthesia in terms of the suppression of movement responses to surgical stimuli.     

Use of haloperidol and azaperone for stress control in roe deer (Capreolus capreolus) captured by means of drive-nets

The physical capture of wild ungulates is performed for different purposes when anaesthesia in field conditions is not possible or advisable. The use of tranquilizers may contribute to improved welfare of captured animals. We studied the effect of haloperidol and azaperone on the stress response of roe deer (Capreolus capreolus) through the study of physiological, haematological and serum biochemical parameters. Thirty one roe deer were drive-net captured and randomly injected with haloperidol (0.30 ± 0.04 mg/kg IM; n = 13), azaperone (0.43 ± 0.07 mg/kg IM; n = 11) or saline (0.5 mL IM; n = 7), and restrained for 3 h. The interindividual variability of heart rate was lower in the treated deer, suggesting a calming effect, and erythrocyte and biochemical parameters indicated vasodilation, splenic sequestration, hemodilution, improvement of renal perfusion and a protective effect on muscle. These results support the suitability of using either azaperone or haloperidol in capture operations of roe deer, in order to reduce stress and prevent its adverse effects.     

Rectal prolapse associated with a healed pelvic fracture in a pregnant free-ranging African black rhinoceros (Diceros bicornis). Part 1: anaesthesia

Anaesthesia was required in a heavily-pregnant, adult, free-ranging African black rhinoceros Diceros bicornis with a rectal prolapse for examination and possible treatment. The animal was immobilised with 4.5 mg etorphine and 60 mg azaperone. For continued observation, the immobilised animal was transported to a boma. Additional etorphine and azaperone were administered to keep the animal anaesthetised during treatment and transport. In addition, 15 mg nalorphine was administered during this time to improve ventilation and reduce muscle rigidity. Sixty hours later, in preparation for surgery, 2.5 mg etorphine and 40 mg azaperone were administered, followed by endotracheal intubation and halothane anaesthesia. During anaesthesia, a decrease in tidal volume was observed. Venous blood-gas analysis indicated a decrease in the oxygen partial pressure, and a mixed respiratory and metabolic acidosis. Cardiac arrest was preceded by an increase in heart rate and tidal volume after 80 min of inhalation anaesthesia.     

Minimum alveolar concentration for blunting adrenergic responses (MAC-BAR) of sevoflurane in dogs

It is well known that heart rate or arterial blood pressure may increase in response to surgical stimulation despite the absence of a purposeful movement. However, there is limited information regarding anesthetic requirement for blunting adrenergic response in dogs. This study was designed to compare the minimum alveolar concentrations of sevoflurane required to prevent autonomic response (MAC-BAR) and purposeful movement (MAC) in dogs. Sevoflurane MAC-BAR and MAC were determined in 5 beagle dogs by judging dogs' response to a noxious electrical stimulus applied to the gingiva. The sevoflurane MAC-BAR was significantly higher than MAC (3.33 ± 0.48 vs 2.10 ± 0.28%, P=0.005). These results suggested that autonomic responses occurred at sevoflurane anesthetic concentrations at which purposeful movements were absent.     

The effect of carazolol on the cardiovascular responses to adrenaline in stress sensitive pigs

The effect of propranolol, carazolol and acebutolol on the heart rate and blood pressure responses to intravenous adrenaline were examined in conscious Pietrain pigs. All three drugs blocked the tachycardia and vasodilatory responses to adrenaline and induced an increase in vasopressor responsiveness. The likely complications from using non-cardioselective beta blockers for preventing stress-induced deaths in pigs are discussed.     

Effect of verapamil on cardiac chronotropic response to vagal stimulation in neonatal pigs

The effects of verapamil on the chronotropic response to vagal stimulation in young pigs anesthetized with sodium pentobarbital (30 mg/kg of body weight, intraperitoneally) was evaluated. After bilateral vagotomy, the administration of verapamil (loading dose of 100 micrograms/kg, followed by 2 micrograms/kg/min infusion) resulted in a significant (P less than 0.05) reduction in heart rate (HR) and mean arterial blood pressure. Cardiac frequency responses to vagal stimulation were obtained by stimulating the distal end of the right vagus nerve at selected frequencies (5, 10, 15, and 20 Hz) with supramaximal voltage (10 to 15 V) and constant duration (2 ms). The HR was measured after 15 s at each level of stimulation. The slopes of decrease in HR to the frequency of vagal stimulation were significantly (P less than 0.05) reduced after verapamil as compared with its controls. After atropine (0.5 mg/kg), the vagally induced tachycardia was partially attenuated by verapamil, but was completely eliminated by beta blockade with propranolol (1 mg/kg). These findings indicated that verapamil may influence the parasympathetic control of the heart in young pigs.