Retrospective and prospective assessment of butorphanol, azaperone and medetomidine (BAM™) for immobilisation of feral horses (Equus ferus caballus).

BACKGROUND: Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses. OBJECTIVES: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses. STUDY DESIGN: Retrospective and prospective descriptive studies. METHODS: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6-year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamine was given intravenously (iv). Induction and recovery time and quality via a standardised rubric (1 = very poor; 5 = excellent) and visual analogue scale (VAS), need for additional darts, weight tape measurement and serial physiological parameters were recorded. Serial arterial blood gas analysis was performed during recumbency. Following castration, horses were given 0.1 mg/kg bwt atipamezole (25% iv and 75% im) and allowed to recover unaided. RESULTS: Retrospectively, 28 horses were successfully immobilised with BAM™ without a major complication. Prospectively, eight horses were given a median (range) actual BAMTM dose of 0.0143 (0.0127-0.0510) mL/kg bwt. Three of eight horses needed 1, 2 or 5 additional darts. Median (range) time to recumbency was 11 (2-44) minutes. Median (range) induction (n = 4) and recovery (n = 6) scores via rubric and VAS were 5 (4-5) and 5 (5-5) and 92 (86-93) and 98 (92-99) cm, respectively. Four of seven horses were hypoxaemic at ≥1 time point with otherwise acceptable physiological parameters. Following atipamezole, median (range) time to sternal recumbency and standing was 12 (2-18) and 17 (11-52) minutes, respectively (n = 6). MAIN LIMITATIONS: The sample size was small. Data could not be collected before darting or after recovery. Some data were missing from retrospective analysis. CONCLUSIONS: Intramuscular BAM™ with iv ketamine provided chemical restraint suitable for field castration of feral horses with no mortality. Hypoxaemia occurred in the majority of horses.

Assessment of butorphanol-azaperone-medetomidine combination as anesthesia for semen collection and evaluation of semen quality in white-tailed deer (Odocoileus virginianus).

The aim of this current study was to evaluate the level of anesthesia produced by a combination of butorphanol-azaperone-medetomidine (BAM) for semen collection by electroejaculation on captive white-tailed bucks (Odocoileus virginianus). Ten male white-tailed deer, weighing 68.2-115.9kg, ranging in age from one to four years were randomly selected from housing pens and anesthetized with the BAM drug combination at a dose volume of 2.0mL each. Semen was collected from each animal using a standard cervid electroejaculation protocol while under BAM anesthesia. Physiological data was recorded following induction of anesthesia and during semen collection. Collected ejaculates were prepared for analysis using a standard extender protocol for cryopreservation. Eleven sperm viability parameters were quantified for each sample using a Computerized Assisted Sperm Analysis system, including total seminal volume; sperm concentration and total sperm number. kinematic parameters of motile spermatozoa were also assessed. Results demonstrated that BAM provided an effective plane of anesthesia for successful collection of viable sperm. Measured physiological variables of heart rate, respiration and body temperature all remained within safe, normal limits. Data recorded on semen characteristics from all collected ejaculates correlated well with key traits determined to be important for successful fertilization through measurement of total semen volume; sperm concentration; total sperm number; and kinematic parameters of motile spermatozoa. There were no serious adverse events. This field study indicates that BAM anesthesia is suitable for semen collection in white-tailed deer.

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats.

OBJECTIVE: To assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. STUDY DESIGN: Experimental, prospective, blinded, randomized study. ANIMALS: Sixty healthy adult female cats with a (mean±standard deviation) weight of 3.3±0.6 kg. METHODS: Cats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg(-1); buprenorphine 20 µg kg(-1); medetomidine 2 µg kg(-1); tramadol 2 mg kg(-1), and ketoprofen 2 mg kg(-1). Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15-30, 30-45, 45-60, 60-75, 90-105 and 120-135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman's test. Differences amongst treatments were assessed using independent Kruskal-Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. RESULTS: Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p<0.05) only for tramadol at 60-75 and 90-105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. CONCLUSIONS AND CLINICAL RELEVANCE: The CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.

The use of a Corophium volutator chronic sediment study to support the risk assessment of medetomidine for marine environments.

Chronic sediment studies were conducted using the marine amphipod Corophium volutator as part of an environmental risk assessment of the novel antifouling compound medetomidine. Two studies were performed, starting with neonates of less than 7 d old. A 28-d study considered endpoints of survival and growth (length and wet wt) and a 76-d study looked at survival, growth (length and wet wt), and reproduction (number of gravid females and neonates). Medetomidine was dosed via the sediment at nominal test concentrations of 1.0 µg/kg, 3.2 µg/kg, 10 µg/kg, 32 µg/kg, and 100 µg/kg (dry wt). In the 28-d growth study, a significant increase in mortality was observed at 32 µg/kg and 100 µg/kg. In the 76-d reproduction study, there were significant adverse effects on survival (32 µg/kg and 100 µg/kg), growth (100 µg/kg), and reproduction (100 µg/kg). The overall lowest-observed-effect concentration was 32 µg/kg medetomidine. For this test substance the increased study duration did not increase the overall sensitivity of the test. The present study suggests that the predicted sediment environmental concentration (PECsediment ) of 0.003 µg/kg for medetomidine would not be expected to cause adverse effects on the life history of C. volutator.

Assessment of the effects of intramuscular administration of alfaxalone with and without medetomidine in Horsfield's tortoises (Agrionemys horsfieldii).

OBJECTIVE: To characterise four different intramuscular (IM) anaesthetic protocols, two with alfaxalone and two with alfaxalone in combination with medetomidine in terrestrial tortoises. STUDY DESIGN: Blinded, randomized, cross-over experimental study. ANIMALS: Nine healthy adult male Horsfield's tortoises (Agrionemys horsfieldii). METHODS: Each tortoise was randomly assigned to one of four different protocols: 1) 10 mg kg(-1) alfaxalone; 2) 10 mg kg(-1) alfaxalone + 0.10 mg kg(-1) medetomidine; 3) 20 mg kg(-1) alfaxalone; and 4) 20 mg kg(-1) alfaxalone + 0.05 mg kg(-1) medetomidine. During the experiment, the following variables were recorded: heart rate; respiratory rate; peripheral nociceptive responses; muscle strength; ability to intubate; palpebral, corneal and tap reflexes; and cloacal temperature. RESULTS: Protocols 1 and 2 resulted in moderate sedation with no analgesia, and moderate to deep sedation with minimal analgesia, respectively. Protocols 3 and 4 resulted in deep sedation or anaesthesia with variable analgesic effect; these two protocols had the longest total anaesthetic time and allowed intubation in 6/9 and 8/9 tortoises respectively. The total anaesthesia/sedation time produced by alfaxalone was significantly increased (p < 0.05) by the addition of medetomidine. There were no significant differences regarding time to plateau phase and duration of plateau phase. Baseline heart rate of 53 ± 6 beats minute(-1) decreased significantly (p < 0.05) with all protocols, and was lower (p < 0.05) in protocols 3 and 4. Heart rate increased after atipamezole administration, but the increase was transient. In two tortoises, extreme bradycardia with no cardiac activity for 10 minutes was observed with protocols 3 and 4. CONCLUSION AND CLINICAL RELEVANCE: Alfaxalone 10 and 20 mg kg(-1) IM can be used for sedation for non-painful procedures. Alfaxalone in combination with medetomidine can be used for deeper sedation or anaesthesia, but the observed respiratory and cardiovascular depression may limit its use.

The use and assessment of ketamine-medetomidine-butorphanol combinations for field anaesthesia in wild European badgers (Meles meles).

OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN: Prospective randomized 'blinded' experimental trial. METHODS: The quality of induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed in 93 badgers, given either one of three ketamine (K)-medetomidine (M)-butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B - M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1), or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the combination administered. Physiological variables (heart and respiratory rates and rectal temperature) were measured at 5-minute intervals during anaesthesia. Gingival mucus membrane colour was also recorded. RESULTS: Induction to anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality did not differ between techniques. Ketamine used alone gave the poorest score for anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane colour were higher in animals anaesthetized with ketamine alone. Rectal temperature did not differ significantly between the techniques at any time during anaesthesia. Ketamine used alone produced the poorest quality of recovery. CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame several side effects associated with ketamine anaesthesia, but at the expense of more variable induction times, lower HRs, and poorer mucus membrane coloration.

Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit.

OBJECTIVE: To study the effects of ketamine and two doses of medetomidine administered by two routes of injection in a genetically diverse population of rabbits. STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: One hundred and five domestic rabbits of mixed breed, sex and age. MATERIALS AND METHODS: Rabbits undergoing orchiectomy or ovariohysterectomy received ketamine (15 mg kg(-1)) combined with medetomidine at 0.25 or 0.5 mg kg(-1), by subcutaneous (SC) or intramuscular (IM) injection. Anaesthesia was supplemented with 1.5-2% isoflurane when signs of regular jaw movements and/or slight limb twitching indicated inadequate anaesthesia. Heart and respiratory rate, blood oxygen saturation, end-tidal carbon dioxide concentration and rectal temperature were monitored at several time points. Duration of surgical anaesthesia and anaesthesia time were measured. At completion of surgery, atipamezole (1.0 or 0.5 mg kg(-1), IM or SC) was administered. STATISTICAL ANALYSES: MANOVA was used to compare variables over time between males and females, anaesthetic doses and routes of drug administration. RESULTS: All reflexes were lost significantly more rapidly after IM drug administration (p < 0.05). The times (in minutes) from drug injection to loss of reflexes for the respective groups were: righting reflex: 6.3 (15.0 + 0.25, SC), 5.5 (15.0 + 0.5, SC), 2.9 (15.0 + 0.25, IM) and 2.3 (15.0 + 0.5, IM); ear pinch: 9.2, 8.5, 4.8, 3.6; pedal withdrawal: 12.8, 10.4, 6.6, 5.2. Heart and respiratory rates during surgery did not differ between groups, however the highest end-tidal CO(2) concentration during surgery was significantly affected by dose, with the highest concentration occurring in group 15.0 + 0.5 IM. The number of animals requiring isoflurane tended to decrease with increasing dose of anaesthetic and significantly more females required supplementation than males (p < 0.05). Recovery from anaesthesia (return of righting reflex) was not significantly different between dose groups (p > 0.1) but was more rapid in animals given IM atipamezole (13.6 +/- 13 versus 21 +/- 17, p = 0.037). No anaesthetic-related mortality occurred and all but three animals recovered uneventfully. Five animals were killed whilst under anaesthesia because of unrelated disease. CONCLUSION AND CLINICAL RELEVANCE: Ketamine-medetomidine combinations reliably produced surgical anaesthesia in domestic rabbits that could easily be deepened for brief periods with low concentrations of isoflurane. Subcutaneous administration was better tolerated, but the speed of induction was slower compared with IM injection. Atipamezole was an effective antagonist and produced most rapid effects when administered IM.

Cardiopulmonary assessment of medetomidine, ketamine, and butorphanol anesthesia in captive Thomson's gazelles (Gazella thomsoni).

This investigation evaluated the cardiopulmonary effects of medetomidine, ketamine, and butorphanol anesthesia in captive juvenile Thomson's gazelles (Gazella thomsoni). Butorphanol was incorporated to reduce the dose of medetomidine necessary for immobilization and minimize medetomidine-induced adverse cardiovascular side effects. Medetomidine 40.1 +/- 3.6 microg/kg, ketamine 4.9 +/- 0.6 mg/kg, and butorphanol 0.40 +/- 0.04 mg/kg were administered intramuscularly by hand injection to nine gazelles. Times to initial effect and recumbency were within 8 min postinjection. Cardiopulmonary status was monitored every 5 min by measuring heart rate, respiratory rate, indirect blood pressure, end-tidal CO2, and indirect oxygen-hemoglobin saturation by pulse oximetry. Venous blood gases were collected every 15 min postinjection. Oxygen saturations less than 90% in three gazelles suggested hypoxemia. Subsequent immobilized gazelles were supplemented with intranasal oxygen throughout the anesthetic period. Sustained bradycardia (<60 beats per minute, as compared with anesthetized domestic calves, sheep, and goats) was noted in eight of nine gazelles. Heart and respiratory rates and rectal temperatures decreased slightly, whereas systolic, mean, and diastolic blood pressure values were consistent over the anesthetic period. Mild elevations in end tidal CO2 and PCO2 suggested hypoventilation. Local lidocaine blocks were necessary to perform castrations in all seven of the gazelles undergoing the procedure. Return to sternal recumbency occurred within 7 min and return to standing occurred within 12 min after reversal with atipamezole (0.2 +/- 0.03 mg/kg) and naloxone (0.02 +/- 0.001 mg/kg). Medetomidine, ketamine, and butorphanol can be used to safely anesthetize Thomson's gazelles for routine, noninvasive procedures. More invasive procedures, such as castration, can be readily performed with the additional use of local anesthetics.

Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice.

1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 52 degrees C water bath with mean ED50 values of 99.9+/-14.5 (alpha2A), 94.6+/-17.8 (alpha2B) and 116.0/-17.1 (alpha2C) microg kg(-1), i.p. 3. In comparison to the WT controls, Dex (100-1000 microg kg(-1), i.p.), was completely ineffective as an antinociceptive agent in the tail immersion test in the alpha2A AR D79N mutant animals. Conversely, in the alpha2B AR and alpha2C AR knock-outs, Dex produced a dose-dependent antinociceptive effect that was not significantly different from that observed in WT controls, with ED50 values of 85.9+/-15.0 (P>0.05 vs WT control) and 226.0+/-62.7 (P>0.05 vs WT control) microg kg(-1) i.p., respectively. 4. Dex (10-300 microg kg(-1), i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the alpha2A, alpha2B and alpha2C AR WT control animals with ED50 values of 30.1+/-9.0, 23.5+/-7.1 and 32.3+/-4.6 microg kg(-1), i.p., respectively. Again, Dex (100-1000 microg kg(-1), i.p.) was ineffective at modulating motor behaviour in the alpha2A AR D79N mutants. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED50 values of 29.1+/-6.4 (P>0.05 vs WT control) and 57.5+/-11.3 (P>0.05 vs WT control) microg kg(-1), respectively. 5. Dex was also found to produce a dose-dependent reduction in body temperature in the alpha2A, alpha2B and alpha2C AR WT control mice with ED50 values of 60.6+/-11.0, 16.2+/-2.5 and 47.2+/-9.1 microg kg(-1), i.p., respectively. In the alpha2A AR D79N mutants, Dex had no effect on body temperature at a dose (100 microg kg(-1), i.p.) that produced a significant reduction (-6.2+/-0.5 degrees C; P<0.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 microg kg(-1), i.p) produced a small, but statistically significant decrease in temperature corresponding to -1.7+/-0.4 degrees C and -2.4+/-0.3 degrees C (both P<0.01 vs vehicle), respectively. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED50 values of 28.4+/-4.8 (P>0.05 vs WT control) and 54.1+/-8.0 (P>0.05 vs WT control) microg kg(-1), respectively. 6. In conclusion, the data are consistent with the alpha2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This profile would appear to indicate that an alpha2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.

Assessment of orocaecal transit time in cats by the breath hydrogen method: the effects of sedation and a comparison of definitions.

Oro-caecal transit times (OCTTs) were assessed in 10 healthy adult cats by the lactulose breath hydrogen method with either no sedation (group A), or after the intramuscular administration of three sedative regimens: a combination of acetylpromazine at 0.1 mg kg-1 with buprenorphine at 10 micrograms kg-1 (group B), ketamine at 5 mg kg-1 with midazolam at 0.1 mg kg-1 (group C), or medetomidine at 50 micrograms kg-1 (group D). For each test, the OCTT was defined by four methods: a visual assessment, the first maintained 4 ppm increase in hydrogen production, and the first maintained 0.5 ml hr-1 increase in hydrogen production assessed by two cumulative sum methods. Depending on the definition, the median OCTTs of the cats were between 113 and 131.5 minutes in group A, 86.5 and 97.5 minutes in group B, 218 and 235.5 minutes in group C and 86.5 and 97.5 minutes in group D. By two of the definitions, the median OCTTs in group C were significantly longer than in group A (P < or = 0.037) and approached significance by the other two definitions. The use of sedatives significantly increased the inter-individual variability of the OCTTs, particularly in groups C and D. There were significant differences between the median OCTTs defined by the four different methods, but all the methods were very highly and significantly correlated (rs < or = 0.9503, P < 0.0001).

Assessment of the sedative effect of medetomidine and determination of its optimal dose in thoroughbred horses.

The present study was carried out to assessing the sedative effect of medetomidine and determining its optimal dose in thoroughbred horses. Excessive ataxia after sedative treatment is dangerous for horses. Therefore three doses which may cause sufficient sedation with only mild ataxia were examined. Response to stimulation and the severity of ataxia suggested that 7.5 micrograms/kg BW, i.v., is optimal.

Assessment of the sedative effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, with analysis of saccadic eye movements.

Single intravenous doses (0.5 microgram/kg and 1.0 microgram kg) of dexmedetomidine (4(5)-(1-(2,3-dimethylphenyl)ethyl)imidazole), a selective alpha 2-adrenoceptor agonist, and saline placebo were administered to six healthy volunteers (4 males and 2 females) in a double-blind, placebo-controlled cross-over study. The effects on vigilance were assessed using both subjective estimation (visual analogue scale, VAS) and objective tests (critical flicker fusion frequency, CFF; the Maddox wing; saccadic eye movement analysis). Dose-dependent subjective sedation was seen in VAS measurements, and impairment of vigilance was observed in CFF, Maddox wing and peak saccadic velocity, while saccade latency was not influenced by dexmedetomidine. The changes in vigilance were concurrent with moderate reductions in blood pressure and heart rate. CFF, the Maddox wing and peak saccadic velocity all proved sensitive in the assessment of sedation induced by dexmedetomidine.