The behaviour of healthy awake cats following intravenous and intramuscular administration of midazolam

The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short-lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administration.     

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.     

Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration

Objective To examine the effect of dose and route of administration on the sedative‐hypnotic effects of midazolam. Design Prospective randomized controlled study Animals Six indigenous, African bred goats. Methods Pilot studies indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg^?1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg^?1 and 1.2 mg kg^?1, respectively. These doses and routes of administration were compared with a saline placebo in a randomized block design in the main experiment, and the sedative‐hypnotic effects evaluated according to pre‐determined scales. Results Intramuscular midazolam produced sedation with or without sternal recumbency in all animals with the peak effect occurring 20 minutes after administration. The scores for IM sedation with midazolam were significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg kg^?1 resulted in hypnosis, and at 1.2 mg kg^?1 increased reflex suppression was observed. The maximum scores for hypnosis at both doses were obtained 5 minutes after IV injection. The mean (± SD) duration of lateral recumbency was 10.8 (± 3.8) minutes after IV midazolam (0.6 mg kg^?1) compared to 20 (± 5.2) minutes after midazolam at 1.2 mg kg^?1. Compared to baseline, the heart rate increased significantly (p < 0.05) after high dose IV midazolam. Conclusion Intramuscular midazolam (0.6 mg kg^?1) produced maximum sedation 20 minutes after injection. Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the IV dose from 0.6 to 1.2 mg kg^?1 resulted in increased reflex suppression and duration of hypnosis. Clinical relevance For a profound effect with rapid onset midazolam should be given IV in doses between 0.6 and 1.2 mg kg^?1.     

Clinical evaluation of intranasal benzodiazepines, alpha-agonists and their antagonists in canaries

OBJECTIVE: To evaluate the effects of intranasal benzodiazepines (midazolam and diazepam), alpha(2)-agonists (xylazine and detomidine) and their antagonists (flumazenil and yohimbine) in canaries. STUDY DESIGN: Prospective randomized study. ANIMALS: Twenty-six healthy adult domesticated canaries of both sexes, weighing 18.3 +/- 1.0 g. METHODS: In Study 1 an attempt was made to determine the dose of each drug that allowed treated canaries to be laid in dorsal recumbency for at least 5 minutes, i.e. its effective dose. This involved the evaluation of various doses, during which equal volumes of the tested drug were administered slowly into each nostril. In study 2 the onset of action, duration and quality of sedation induced by each drug at its effective dose were evaluated. The efficacy of flumazenil and yohimbine in antagonizing the effects of the sedative drugs was also studied. RESULTS: In study 1 administration of 25 microL per nostril diazepam (5 mg mL(-1) solution) or midazolam (5 mg mL(-1) solution) to each bird caused adequate sedation within 1-2 minutes; birds did not move when placed in dorsal recumbency. After administration of 12 microL per nostril of either xylazine (20 mg mL(-1)) or detomidine (10 mg mL(-1)), birds seemed heavily sedated and assumed sternal recumbency but could not be placed in dorsal recumbency. Higher doses of xylazine (0.5 mg per nostril) or detomidine (0.25 mg per nostril) prolonged sedation but did not produce dorsal recumbency. In study 2 in all treatment groups, onset of action was rapid. Duration of dorsal recumbency was significantly longer (p < 0.05) with diazepam (38.4 +/- 10.5 minutes) than midazolam (17.1 +/- 2.2 minutes). Intranasal flumazenil (2.5 microg per nostril) significantly reduced recumbency time. Duration of sedation was longer with alpha(2)-agonists compared with benzodiazepines. Detomidine had the longest duration of effect (257.5 +/- 1.5 minutes) and midazolam the shortest (36.9 +/- 2.4 minutes). Nasally administered flumazenil significantly reduced the duration of sedation with diazepam and midazolam while yohimbine (120 microg per nostril) effectively antagonized the effects of xylazine and detomidine. CONCLUSION: Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries.     

Determination of a sedative dose and influence of midazolam on cardiopulmonary function in Canada geese

Midazolam HCl (1.0 or 2.0 mg/kg of body weight) was administered IM to 6 Canada geese to determine a sedative dose that would allow positioning for radiologic examination. The effects of both test doses on cardiopulmonary function were evaluated at 5, 10, 15, 20, 30, and 40 minutes after drug administration and were compared with 2 end-tidal isoflurane concentrations (1.5 and 2.5%). The 2.0 mg/kg dosage induced moderate sedation at 15 and 20 minutes; sedation was adequate for positioning the geese. Sedation induced by the 1.0 mg/kg dosage was inadequate. The effects of both test doses on blood pressure, heart rate, and temperature were not significantly different from each other and from baseline data. Respiratory rate increased significantly (P less than 0.05) at 10, 15, 20, and 30 minutes with the 2.0 mg/kg dosage, and at 15 and 20 minutes with the 1.0 mg/kg dosage. Blood pressure and respiratory rate were significantly (P less than 0.05) decreased with isoflurane when compared with baseline data and the midazolam test doses. The results of this study indicate that midazolam at a dosage of 2.0 mg/kg induces adequate sedation with minimal cardiopulmonary changes, and, as an alternative to general anesthesia with isoflurane, provides a satisfactory level of restraint for radiography.     

Romifidine-ketamine anaesthesia in atropine and triflupromazine pre-medicated buffalo calves

The study was conducted on 10 buffalo calves with a weight of 98.5 +/- 3.9 kg and age 9.7 +/- 1.3 months. Ten trials of two treatments were carried out using a randomized block design. Atropine at the dose of 0.02 mg/kg bodyweight was administered in both the groups. The animals of group I received romifidine at the dose of 10 microg/kg i.v., 10 min after atropine administration, whereas, animals of group II received triflupromazine at the dose of 0.3 mg/kg i.m. and 10 min later romifidine at the dose of 10 microg/kg i.v. immediately followed by ketamine at the dose of 5 mg/kg i.v. The onset of action of romifidine in group I occurred within 2 min and the animals remained under mild sedation for 31 +/- 4.8 min. In group II, the triflupromazine-romifidine-ketamine combination induced anaesthesia for 14 +/- 2.3 min. Hypothermia, significant bradycardia and respiratory depression was noticed in both groups at different time intervals.     

Evaluation of Pentobarbital as a Drug for Standing Sedation in Cattle

Pentobarbital (1.0, 1.5, and 2.0 mg/kg intravenously [IV]) was administered to four adult cows to determine a dose suitable for producing standing sedation in adult cattle, and to evaluate its effects on cardiopulmonary function and rumen motility. The response was assessed after 15, 30, 60, and 90 minutes. The 1.0 and 1.5 mg/kg doses induced mild sedation at 15 and 30 minutes, and no sedation at 60 and 90 minutes. The 2.0 mg/kg dose produced moderate sedation at 15 and 30 minutes, and mild sedation at 60 minutes. The 2.0 mg/kg dose was judged to be the most suitable. The effects of pentobarbital (2.0 mg/kg IV) on heart rate, blood pressure, respiratory rate, blood gases, and rumen motility were measured in five cows during a 90 minute period. Respiratory rate was significantly depressed at 15, 30, and 60 minutes, but there were no significant changes in the other variables. Pentobarbital (2.0 mg/kg IV) is reliable in adult cattle for standing sedation of short duration.     

The effects of diazepam or midazolam on the dose of propofol required to induce anaesthesia in cats

ObjectivesAssess effects of benzodiazepine administration on the propofol dose required to induce anaesthesia in healthy cats, investigate differences between midazolam and diazepam, and determine an optimal benzodiazepine dose for co-induction.Study designProspective, randomised, blinded, placebo-controlled clinical trial.AnimalsNinety client-owned cats (ASA I and II) with a median (interquartile range) body mass of 4.0 (3.4–4.9) kg.MethodsAll cats received 0.01 mg kg⁻¹ acepromazine and 0.2 mg kg⁻¹ methadone intravenously (IV). Fifteen minutes later, sedation was scored on a scale of 1–5, with 5 indicating greatest sedation. Propofol, 2 mg kg⁻¹, administered IV, was followed by either midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg⁻¹ or saline 0.1 mL kg⁻¹. Further propofol was administered until endotracheal intubation was possible. Patient signalment, sedation score, propofol dosage and adverse reactions were recorded.ResultsMidazolam and diazepam (all doses) significantly reduced the propofol dose required compared with saline (p < 0.001). There was no difference between midazolam and diazepam in propofol dose reduction (p = 0.488). All individual doses of midazolam reduced propofol requirement compared with saline (0.2 mg kg⁻¹, p = 0.028; 0.3 mg kg⁻¹, p = 0.006; 0.4 mg kg⁻¹, p < 0.001; 0.5 mg kg⁻¹, p = 0.009). Diazepam 0.2 mg kg⁻¹ did not reduce the propofol dose compared with saline (p = 0.087), but the remaining doses did (0.3 mg kg⁻¹, p = 0.001; 0.4 mg kg⁻¹, p = 0.032; 0.5 mg kg⁻¹, p = 0.041). Cats with sedation scores of 3 required less propofol than cats with scores of 2 (p = 0.008). There was no difference between groups in adverse events.Conclusions and clinical relevanceMidazolam (0.2–0.5 mg kg⁻¹) and diazepam (0.3–0.5 mg kg⁻¹) administered IV after 2 mg kg⁻¹ propofol significantly reduced the propofol dose required for tracheal intubation.     

Effects of intramuscular and intranasal administration of midazolam–dexmedetomidine on sedation and some cardiopulmonary variables in New Zealand White rabbits

ObjectiveTo compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.Study designA randomized, crossover experimental study.AnimalsA total of eight healthy New Zealand White rabbits, aged 6–12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).MethodsThe animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg^–1) with midazolam (2 mg kg^–1) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO₂), mean noninvasive arterial pressure (MAP), respiratory frequency (f_R) and rectal temperature were measured before drug administration (baseline), T₀ (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.ResultsThe PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO₂ progressively decreased over time in both treatments. f_R was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).Conclusions and clinical relevanceCombination of dexmedetomidine (0.1 mg kg^–1) and midazolam (2 mg kg^–1) decreased f_R, PR and SpO₂ regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.     

Meperidine prolongs lidocaine caudal epidural anaesthesia in the horse

The aim of the study was to evaluate and compare the effects of caudal epidural administration of meperidine (MP), lidocaine (LD), and a combination of the two (MPLD) in six mature saddle horses. Horses were randomly assigned to receive three treatments (MP 0.3 mg/kg; LD 0.2 mg/kg; and MPLD: MP 0.3 mg/kg and LD 0.2 mg/kg), with at least 1 week between treatments. Drugs were injected into the epidural space between the first and second coccygeal areas in conscious standing horses. Analgesia, ataxia, sedation, cardiovascular and respiratory effects, and rectal temperature were recorded at different intervals before (baseline) and after administration. Epidural administration of MPLD resulted in a longer duration of analgesia of the tail, perineum, and upper hind limb regions than did administration of MP or LD alone.     

Administration of a low dose tiletamine-zolazepam combination to cats

A tiletamine-zolazepam mixture was administered subcutaneously at doses of 2.5 mg/kg, 5.0 mg/kg and 7.5 mg/kg to fifty-nine cats. The response to drug administration, effect on heart rate, pulse quality, respiratory rate and temperature, and intensity and duration of sedation were recorded. As the tiletamine-zolazepam dose was increased, intensity and duration of sedation increased. At the lowest dose, some cats became excited rather than sedated. Heart rate and respiratory rate changed minimally, but body temperature decreased.     

Effects of medetomidine and midazolam alone or in combination on the metabolic and neurohormonal responses in healthy cats

The purpose of this study was to investigate the effects of a medetomidine-midazolam combination on some neurohormonal and metabolic variables in healthy cats. Five cats were used repeatedly in each of 5 groups, which were injected intramuscularly with physiological saline solution (control), 0.5 mg/kg of midazolam, 40 microg/kg of medetomidine, 80 microg/kg of medetomidine, and 40 microg/kg of medetomidine plus 0.5 mg/kg of midazolam. Blood samples were taken 10 times over 24 h from a catheter introduced into the jugular vein. Plasma concentrations of glucose, insulin, glucagon, cortisol, nonesterified fatty acids (NEFAs), norepinephrine, and epinephrine were determined. In addition, the duration of lateral recumbency, rectal temperature, heart rate, and respiratory rate were examined. The combination of medetomidine and midazolam enhanced the duration of lateral recumbency and reduced the hyperglycemia induced by medetomidine alone. Recovery from hypoinsulinemia induced by the medetomidine-midazolam combination tended to be more rapid than when the same dose of medetomidine was used alone. The decrease in plasma norepinephrine levels induced by medetomidine alone was diminished by the addition of midazolam. Midazolam alone did not significantly change the plasma glucose, insulin, glucagon, cortisol, epinephrine, or NEFA concentration, but increased the norepinephrine concentration. This study revealed that the combination of medetomidine and midazolam produces minimal neurohormonal and metabolic changes when compared with medetomidine alone in cats.     

Sedation and Pain Management with Intravenous Romifidine−Butorphanol in Standing Horses

The objective of this study was to determine the sedation, analgesia, and clinical reactions induced by an intravenous combination of romifidine and butorphanol in horses. The study was conducted on six saddle horses weighing 382 to 513 kg (mean ± SD; 449 ± 54 kg) and aged 6 to 14 years. The horses each underwent three treatments: intravenous romifidine 0.1 mg/kg body weight (RM; mean dose, 4.5 mL); intravenous butorphanol 0.05 mg/kg body weight (BT; mean dose, 2.4 mL); and intravenous romifidine 0.1 mg/kg body weight plus butorphanol 0.05 mg/kg body weight (RMBT; mean dose, 7.0 mL). The order of treatments was randomized. Heart rate, arterial pressure, respiratory rate, rectal temperature, sedation, and analgesia were measured at two times before treatments, 15 minutes apart (times –15 and 0) and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, and 180 minutes after drug administration. The onset of sedation was approximately 5 minutes after intravenous injection of RM and RMBT, whereas BT did not present this effect. The duration of complete sedation was approximately 60 minutes for RMBT and approximately 35 minutes for RM. The RMBT treatment provided 30 minutes and the RM treatment 20 minutes of complete analgesia. Heart rate decreased significantly (P < .05) from basal values in the RM and RMBT treatments. Only RM caused significant decreases (P < .05) in the respiratory rate. Arterial pressure did not change significantly (P > .05) in any treatment. Intravenous administration of a romifidine−butorphanol combination to horses resulted in longer duration of sedation and analgesia than administration of romifidine or butorphanol alone. These effects probably resulted from a synergistic effect of the two drugs.     

Sedative Effects of Intranasal Midazolam and Dexmedetomidine in 2 Species of Tortoises (Chelonoidis carbonaria and Geochelone platynota)

The sedative effects of intranasal midazolam and dexmedetomidine were evaluated in 2 tortoise species as a means to facilitate handling and performing diagnostic procedures. Six red-footed tortoises (Chelonoidis carbonaria) and 6 Indian star tortoises (Geochelone platynota) received the following treatments in a randomized order with 2-week washout periods between the treatments: midazolam (0.5 and 1.5 mg/kg), dexmedetomidine (0.05 and 0.15 mg/kg), and saline control. Tortoises were evaluated and scored for sedation (using a previously published subjective method) by blinded observers, and results were averaged for each species and treatment group. Low-dose dexmedetomidine (0.05 mg/kg) in red-footed tortoises resulted in a significantly higher median sedation score at 5 minutes compared with other treatments. Control saline resulted in a higher median sedation score 5 minutes after administration in Indian star tortoises compared with red-footed tortoises. No other significant differences were observed between treatments or between species. The results suggest that intranasal administration of midazolam or dexmedetomidine, at the dosages used in this study, do not provide effective sedation in red-footed tortoises or Indian star tortoises, based on a subjective scoring system.     

Sedative effects of medetomidine in pigs.

Sedative effects of medetomidine, a potent selective and specific alpha 2-adrenoceptor agonist, were evaluated in pigs using 5 different doses (30, 50, 80, 100 and 150 micrograms/kg of body weight) and compared with those of xylazine (2 mg/kg). Atropine (25 micrograms/kg) was mixed with both drugs to prevent severe bradycardia. All drugs were administered intramuscularly. Medetomidine at a dosage of 30 micrograms/kg produced more potent sedation than xylazine. The depth of sedation induced by medetomidine was dose dependent within the range from 30 to 80 micrograms/kg. At 100 or 150 micrograms/kg, the depth of sedation was mostly the similar level to that at 80 micrograms/kg but the duration was prolonged. The degree of muscle relaxation produced by medetomidine also seemed to be dose dependent from 30 to 80 micrograms/kg and was stronger than that produced by xylazine. An increase in the duration of muscle relaxation was dose dependent up to 150 micrograms/kg. No analgesic effect was produced by xylazine, however moderate analgesia was obtained by medetomidine. There were no marked changes in heart rate and respiratory rate during the observation period in pigs of any groups, however mild hypothermia after the administration of both drugs was observed. From these results, medetomidine has a significant and dose-dependent sedative effects which are much more potent than that of xylazine, and a combination of 80 micrograms/kg of medetomidine and 25 micrograms/kg of atropine is suitable for sedation with lateral recumbency and moderate muscle relaxation without notable side effects in pigs.     

Anaesthesia with midazolam/medetomidine/fentanyl in chinchillas (Chinchilla lanigera) compared to anaesthesia with xylazine/ketamine and medetomidine/ketamine

We studied four different drug regimes for anaesthetic management in chinchillas and evaluated and compared their cardiovascular and respiratory effects. In this randomized, cross-over experimental study, seven adult chinchillas, five females, two males [515 +/- 70 (SD) g] were randomly assigned to one of the following groups: group 1 [midazolam, medetomidine and fentanyl (MMF), flumazenil, atipamezole and naloxone (FAN); MMF-FAN] received 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m., and for reversal 0.1 mg/kg flumazenil, 0.5 mg/kg atipamezole and 0.05 mg/kg naloxone s.c. after 45 min; group 2 (MMF) 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m.; group 3 [xylazine/ketamine (X/K)] 2.0 mg/kg xylazine and 40.0 mg/kg ketamine i.m.; and group 4 [medetomidine/ketamine (M/K)] 0.06 mg/kg medetomidine and 5.0 mg/kg ketamine i.m. Reflexes were judged to determine anaesthetic stages and planes. Anaesthesia with X/K and M/K was associated with a prolonged surgical tolerance and recovery period. By reversing MMF, recovery period was significantly shortened (5 +/- 1.3 min versus 40 +/- 10.3 min in MMF without FAN, 73 +/- 15.0 min in X/K, and 31 +/- 8.5 min in M/K). Without reversal, MMF produced anaesthesia lasting 109 +/- 16.3 min. All combinations decreased respiratory and heart rate but compared with X/K and M/K, respiratory and cardiovascular complications were less in the MMF groups. Focussing on the clinical relevance of the tested combinations, completely reversible anaesthesia showed two major advantages: anaesthesia can be antagonized in case of emergency and routinely shortens recovery. In small animals particularly these advantages lead to less complications and discomfort and thus often can be lifesaving. As all analgesic components (medetomidine and fentanyl) are reversed, postoperative analgesia should be provided before reversal of anaesthesia.     

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.     

Intramuscular anesthesia of bonito and Pacific mackerel with ketamine and medetomidine and reversal of anesthesia with atipamezole

OBJECTIVE: To determine anesthetic effects of ketamine and medetomidine in bonitos and mackerels and whether anesthesia could be reversed with atipamezole. DESIGN: Clinical trial. ANIMALS: 43 bonitos (Sarda chiliensis) and 47 Pacific mackerels (Scomber japonica). PROCEDURE: 28 bonitos were given doses of ketamine ranging from 1 to 8 mg/kg (0.5 to 3.6 mg/lb), i.m., and doses of medetomidine ranging from 0.2 to 1.6 mg/kg (0.1 to 0.7 mg/lb), i.m. (ratio of ketamine to medetomidine, 2.5:1 to 20:1). Doses of atipamezole equal to 1 or 5 times the dose of medetomidine were used. The remaining 15 bonitos were used to determine the anesthetic effects of ketamine at a dose of 4 mg/kg (1.8 mg/lb) and medetomidine at a dose of 0.4 mg/kg (0.2 mg/lb). The mackerels were given ketamine at doses ranging from 11 to 533 mg/kg (5 to 242 mg/lb) and medetomidine at doses ranging from 0.3 to 9.1 mg/kg (0.1 to 4.1 mg/lb; ratio of ketamine to medetomidine, 3:1 to 800:1). Doses of atipamezole equal to 5 times the dose of medetomidine were used. RESULTS: I.m. administration of ketamine at a dose of 4 mg/kg and medetomidine at a dose of 0.4 mg/kg in bonitos and ketamine at a dose of 53 to 228 mg/kg (24 to 104 mg/lb) and medetomidine at a dose of 0.6 to 4.2 mg/kg (0.3 to 1.9 mg/lb) in mackerels was safe and effective. For both species, administration of atipamezole at a dose 5 times the dose of medetomidine reversed the anesthetic effects. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a combination of ketamine and medetomidine can safely be used for anesthesia of bonitos and mackerels and that anesthetic effects can be reversed with atipamezole.     

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

Four preanesthetic oral sedation protocols for rhesus macaques (Macaca mulatta).

The efficacies and ease of administration of four oral preanesthetic sedation protocols were compared in 18 adult, male rhesus macaques (Macaca mulatta) to achieve heavy sedation and alleviate anxiety, agitation, and potential trauma associated with remote anesthesia induction. The macaques, with average age and weight of 10 yr and 12.5 kg, respectively, were randomly assigned to one of four groups. Group 1 was given 10 mg/kg tiletaminezolazepam and 0.05 mg/kg medetomidine p.o., group 2 was given 1 mg/kg midazolam and 20 mg/kg ketamine p.o., group 3 was given 20 mg/kg ketamine and 0.05 mg/kg medetomidine p.o., and group 4 was given 3 mg/kg midazolam p.o. All protocols produced effects ranging from mild sedation to no response to noxious stimuli, depending on the success of administration. The mean interval to peak effect was 27-43 min in all groups. Ketamine and medetomidine provided significantly better sedation than midazolam alone; there were no other statistically significant differences among the four protocols. Oral tiletamine-zolazepam and medetomidine provided smooth, mild to moderate sedation with few side effects. The midazolam and ketamine combination resulted in severe ataxia. Orally administered ketamine and medetomidine provided smooth, easily reversible, heavy sedation leading to no response to noxious stimuli. Midazolam alone provided only mild sedation. No statistically significant differences in palatability of the four protocols were identified. Orally administered ketamine and medetomidine (group 3) provided the most consistently heavy sedation. A compounding pharmacy may be able to increase the palatability and level of acceptance of these combinations. Alternatively, oral midazolam syrup is well accepted by some animals and provides a mild sedative and calming effect, which may decrease stress associated with the induction of anesthesia via darting, pole syringes, etc.