Effects of alpha-2-adrenoceptor agonism and antagonism on equine blood insulin and glucose concentrations after oral carbohydrate load.

Alpha-2-adrenoceptor agonist detomidine is a commonly used sedative agent in horses. In addition to the sedative effect, detomidine has been reported to elicit changes in energy metabolism such as hypoinsulinaemia and hyperglycaemia. This study aimed to investigate the effects of detomidine with and without peripherally acting alpha-2-adrenoceptor antagonist vatinoxan on insulin and blood glucose (BG) concentrations in horses after a standard dose of oral carbohydrates. Sixteen horses were assigned to four intravenous treatments in a randomised cross-over design: saline (SAL), detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), and a combination of detomidine and vatinoxan (DET+VAT). Horses were administered corn syrup (0.45 mL/kg) immediately before each treatment. Blood samples were collected until 360 min. The differences between treatments were evaluated with repeated measures analysis of covariance and change from baseline was used as a response. P<0.05 was considered significant. After oral carbohydrate load, DET reduced insulin (median 30 min nadir 3.7, min-max 0.6-7.4 µIU/mL) significantly compared with SAL (P<0.0001; 17.4, 9.3-65.4 µIU/mL) and DET+VAT (P=0.0005; 6.4, 2.9-12.9 µIU/mL). BG increased significantly after DET (peak; 130.5, 8.8-15.8 mmol/L) compared with SAL (P<0.0001; 8.7, 6.9-12.4 mmol/L) and DET+VAT (P<0.0001; 8.5, 6.8-10.6 mmol/L). Vatinoxan alone reduced BG (peak median 7.6, 7.0-9.9 mmol/L) compared with SAL (P=0.02) and delayed insulin responses to carbohydrates. In conclusion, vatinoxan alleviated the detomidine-induced changes (DET+VAT compared to DET) in insulin and BG after oral carbohydrate load. Additionally, vatinoxan is potentially able to modulate BG concentration and insulin response after oral carbohydrate administration in horses, but more research is warranted.

Comparison of two pharmacological protocols for inducing ex copula ejaculation in donkeys.

This study aimed to compare the efficacy of two pharmacological protocols for inducing ex copula ejaculation in donkeys. Seven healthy jacks (male donkeys) aged 4 to 20 years (median 8 years) and weighing 136.2±4.17 kg (mean±SE) were enrolled. Using a crossover design, each jack was subjected in a random order to two treatment protocols (IX and IDO) with an interval of 7 days between the two protocols. Each jack was orally administered 3 mg/kg imipramine hydrochloride followed 2 hours later by intravenous (IV) administration of 1.1 mg/kg xylazine hydrochloride (IX protocol) or 0.02 mg/kg detomidine hydrochloride and 20 IU total dose oxytocin (IDO protocol). The jacks were monitored for behavioral changes and ejaculation up to 3 hours from the beginning of each protocol. A total of 22 ex copula ejaculation replicates were attempted. Both protocols resulted in deep sedation and partial to complete penile protrusion in all jacks. There was no difference in the efficacy with the IX protocol inducing ejaculation in 1 of the 11 replicates and the IDO protocol inducing ejaculation in none of the 11 replicates. The results suggest that neither of the two tested pharmacological protocols were effective in inducing ex copula ejaculation in donkeys.

Effect of constant rate infusion of detomidine with and without vatinoxan on blood glucose and insulin concentrations in horses.

OBJECTIVE: To assess the effects of an α2-adrenoceptor agonist (detomidine) constant rate infusion (CRI) with and without an α2-adrenoceptor antagonist (vatinoxan) CRI on blood insulin and glucose concentrations, heart rate, intestinal borborygmi, and sedation during and after infusion in horses. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: A total of nine healthy, adult Finnhorse mares. METHODS: Horses were treated with an intravenous (IV) detomidine loading dose (0.01 mg kg-1), followed by CRI (0.015 mg kg-1 hour-1), and the same doses of detomidine combined with an IV vatinoxan loading dose (0.15 mg kg-1), followed by CRI (detomidine and vatinoxan; 0.05 mg kg-1 hour-1) with an 18 day washout period. Infusion time was 60 minutes and horses were monitored for 240 minutes after the infusion. Heart rate, borborygmi score and sedation were assessed, and blood glucose, insulin and triglyceride concentrations were measured. Data were analyzed using repeated measures ancova and Wilcoxon signed-rank tests. Values of p < 0.05 were considered statistically significant. RESULTS: Insulin concentration decreased during (median nadir 1.7, range 0.0-2.9 µIU mL-1 at 60 minutes, p < 0.0001) and increased after detomidine CRI (median 36.6, range 11.7-78.4 µIU mL-1 at 180 minutes, p = 0.0001) significantly compared with detomidine and vatinoxan CRI. A significant elevation of blood glucose (peak 11.5 ± 1.6 mmol L-1 at 60 minutes, p < 0.0001) was detected during detomidine CRI. Vatinoxan alleviated the insulin changes and abolished the significant increase in blood glucose. Vatinoxan alleviated the decrease in heart rate (p = 0.0001) during detomidine infusion. No significant differences were detected in sedation scores between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Vatinoxan attenuated the negative adverse effects of detomidine CRI and thus is potentially beneficial when used in combination with an α2-adrenoceptor agonist CRI in horses.

Comparison of two sedation protocols for long electroretinography in horses using the Koijman electrode.

BACKGROUND: In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In these various pursuits, the role of vision plays a crucial role. Electroretinography is the most used test to diagnose diseases of the retinal outer segment. There is a wide variety of devices to perform the electroretinography differing one from each other in the corneal electrode and the light stimulation. The Koijman electrode has been tested in dogs but not in horses. The main purpose of this study was to compare electroretinography parameters from horses sedated with detomidine alone or in combination with butorphanol, during a standardized protocol using the Koijman electrode and RETI-port® system. Seven mares were allocated to the detomidine and detomidine plus butorphanol group in a randomised, controlled, crossover study. Friedman and Willcoxon-signed ranked tests were used to compare the electroretinogram parameters. A Student's t-test was used to compare differences in the number of artefacts to valid values ratio obtained under both sedation protocols. RESULTS: Dark adaptation peaked after 16 min under scotopic conditions in both groups. No significant differences in electroretinogram parameters between groups were observed. During the mixed rod and cone response evaluation under scotopic conditions, all mares made a movement of the head resulting in a high number of artefacts. The detomidine plus butorphanol group showed a non-significant tendency to have fewer artefacts and a longer duration of sedation compared to the detomidine group. CONCLUSIONS: Detomidine alone or combined with butorphanol may be suitable to use Koijman electrode and the RETI-port® to perform a standardized long protocol in horses with some adaptations.

Antinociceptive, Sedative and Excitatory Effects of Intravenous Butorphanol Administered Alone or in Combination with Detomidine in Calves: A Prospective, Randomized, Blinded Cross-Over Study.

(1) Background: The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol 0.1 mg kg-1 alone (SB) or combined with 0.02 mg kg-1 of a detomidine (DB) IV. The antinociceptive effect (trigeminocervical reflex threshold (TCRt)), as well as the behavioral (sedation and excitation) and physiological (heart and respiratory rate) changes were investigated. Five time windows were defined: BL (30 min pre-injection), T1 (0-30 min post-injection (PI)), T2 (31-60 min PI), T3 (61-90 min PI) and T4 (91-120 min PI). (3) Results: Both groups had a significative increase in TCRt at T1-T4 compared to the BL. The TCRt was significatively higher in DB than in SB at T1, T2 and T4. Heart rate decreased significatively in DB compared to that in BL. Calves were significantly more sedated in the DB group, and significantly more excited in the SB group compared to the BL. (4) Conclusions: Butorphanol alone has a statistically significant antinociceptive effect, but it elicits marked excitation, limiting its clinical applicability under this dosing regimen. The co-administration of detomidine eliminated the excitatory effect and induced consistent sedation and a significantly more pronounced antinociceptive effect.

Comparing the effects of intravenous injection and intranasal atomisation of detomidine in sheep.

BACKGROUND: Detomidine is an α-2 agonist sedative drug which reduces the release of norepinephrine in nerves. Administering this drug through intranasal (IN) route could cause direct transmission to the central nervous system. Therefore, IN administration of detomidine would decrease the side effects and the onset of sedation. OBJECTIVES: In this study, IN administration of detomidine in sheep through an atomiser was compared to its IV administration. METHODS: Fifteen mature female sheep with an approximate weight of 49.53 ± 1.72 kg were used. They were randomly divided into three groups: (1) atomising 10 µg/kg (IND10 ); (2) IV 10 µg/kg (IVD) and (3) atomising 30 µg/kg (IND30 ). Following administration, vital signs, electrocardiographic components, sedative score and biochemistry profile were measured after 15, 30 and 60 min, which were compared with the baseline measures. RESULTS: Bradycardia and the percentage of reduction from the baseline value in the respiratory rate were lower in the IND10 group compared to those in the IVD group. There was no significant difference in terms of the temperature and blood oxygen saturation (SpO2 ) among all the groups (p > 0.05). The level of cortisol declined in all the groups, and in the IND30 (60 min), it was significantly different with the baseline value. The level of glucose increased in all the groups compared to the baseline, which was not significant. Insulin concentration was reduced in all the groups, and in the IND30 group, it changed significantly 60 min after the drug administration. Sedation onset time was faster in the IV group. However, sedation scores between the two administration methods were not different, and only a dose-dependent increase was found in the sedation score in the atomisation group. CONCLUSIONS: Our findings revealed that IN atomisation of detomidine triggers similar sedation as its IV administration, which could be used as an alternative method.

Comparing the anti-nociceptive, sedative and clinicophysiological effects of epidural detomidine, detomidine-lidocaine and lidocaine in donkeys.

BACKGROUND: Epidural analgesia using the alpha-2 agonist detomidine (DE), alone or in combination with lidocaine (LD), is frequently employed for standing surgical procedures in horses, but its use has not been evaluated in donkeys. METHODS: In a randomised controlled prospective trial, 24 healthy adult donkeys were assigned to four groups (n = 6), each receiving 40 µg/kg of DE, 0.22 mg/kg of LD, combined DE and LD (DELD) or 0.9% sterile normal saline epidurally. After epidural injection of each treatment, the onset, degree and duration of sedation and anatomical extension of anti-nociception were observed. RESULTS: DE and DELD treatments resulted in complete bilateral analgesia with loss of sensation in the tail, perineum, inguinal area, chest and the caudal aspect of the upper pelvic limb, and extended distally to the dorsal metatarsal area. DE and DELD resulted in a significantly (p < 0.05) longer duration of anti-nociception (110 ± 15.4 min and 141.6 ± 14.7 min, respectively) than LD (75.8 ± 4.9 min). The DELD duration of sedation was significantly (p < 0.05) longer than the DE duration (118.3 ± 19.4 min and 108.3 ± 7.5 min, respectively). LIMITATION: The current study's main limitation is using only one dose of DE. CONCLUSION: DE and DELD produced a very effective, safe and acceptable sedative and analgesic effect in the perineal and inguinal regions of donkeys.

Effects of detomidine or romifidine during maintenance and recovery from isoflurane anaesthesia in horses.

OBJECTIVE: To evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia. STUDY DESIGN: Prospective, randomized, blinded, clinical study. ANIMALS: A total of 63 healthy horses undergoing elective surgery during general anaesthesia. METHODS: Horses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 µg kg-1), maintenance (40 µg kg-1 hour-1) and before recovery (20 µg kg-1). In group D2.5, horses were given detomidine IV for premedication (15 µg kg-1), maintenance (5 µg kg-1 hour-1) and before recovery (2.5 µg kg-1). In group D5, horses were given the same doses of detomidine IV for premedication and maintenance but 5 µg kg-1 prior to recovery. Premedication was combined with morphine IV (0.1 mg kg-1) in all groups. Cardiovascular and blood gas variables, expired fraction of isoflurane (Fe'Iso), dobutamine or ketamine requirements, recovery times, recovery events scores (from sternal to standing position) and visual analogue scale (VAS) were compared between groups using either anova followed by Tukey, Kruskal-Wallis followed by Bonferroni or chi-square tests, as appropriate (p < 0.05). RESULTS: No significant differences were observed between groups for Fe'Iso, dobutamine or ketamine requirements and recovery times. Cardiovascular and blood gas measurements remained within physiological ranges for all groups. Group D5 horses had significantly worse scores for balance and coordination (p = 0.002), overall impression (p = 0.021) and final score (p = 0.008) than group R horses and significantly worse mean scores for VAS than the other groups (p = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine or romifidine constant rate infusion provided similar conditions for maintenance of anaesthesia. Higher doses of detomidine at the end of anaesthesia might decrease the recovery quality.

Cage trapping and field anaesthesia of brown bears as part of nuisance bear management.

The population and distribution of the European brown bear (Ursus arctos) in Slovakia are expanding as bears were observed beyond the southern border of the country in Hungary. This study presents the authors' experience with field anaesthesia of wild brown bears trapped in a custom-made container trap and of free-ranging individuals. A total of 25 bears were captured and translocated using a specially designed metal cage trap. The study compared the effectiveness of three anaesthetic protocols in managing both free-ranging and trapped bears. For juveniles, or small adults up to 70 kg body weight (BW), ketamine-xylazine mixture was used at doses of 3.0-4.0 mg kg-1 ketamine and 1.0-1.5 mg kg-1 xylazine BW. The immobilisation of free-ranging bears, which are usually attracted by municipal solid garbage, was performed remotely using PneuDart darts with 2-3 ml of anaesthetics. For this purpose, tiletamine-zolazepam-detomidine (T-Z-D) was preferred at a dose of 1.7-2.5 (T) mg kg-1, 1.7-2.5 (Z) mg kg-1, and 0.1-0.2 (D) mg kg-1 BW. Induction time was from 7 to 18 min post darting with the average of 12.04 min. The same combination was applied to bears trapped in a container trap, with anaesthesia lasting from 40 to 150 min. If T-Z-D was used, no further anaesthetic was needed. In all cases, anaesthesia was antagonised by atipamezole at a dose of 0.15-0.225 mg kg-1 BW. Atipamezole was injected at a half dose intramuscularly and a half dose subcutaneously at the time when the palpebral reflex reappeared and the bear was able to move his tongue. It was shown that the T-Z-D mixture is a safe, low-volume anaesthetic darting protocol that is reversible, has minimal adverse effects on physiological parameters, and has a sufficient duration. The results can be used to manage large carnivore populations in the Carpathian region.

Pharmacologically Induced Ex Copula Ejaculation in Horses and Donkeys.

Pharmacologically induced ex copula ejaculation is a method used for collection of semen when the traditional methods of semen collection are not feasible. Common indications for this method include health issues that either preclude the physical act of mating or result in impaired erection and ejaculation. The method also offers an alternative when there is a lack of equipment and facilities required for semen collection using the conventional artificial vagina method. A variety of pharmacological protocols for ex copula ejaculation in stallions have been evaluated in both research and clinical settings with no serious side-effects reported. In general, these protocols included tricyclic antidepressants, alpha-2 adrenergic receptor agonists, and smooth muscle stimulators, either individually or in combination. Although there is a lot of variation in the ejaculatory rates among studies, a combination of imipramine and xylazine appears to be an effective option for inducing ejaculation in stallions. In cases where this protocol is not successful, collections should be reattempted using a combination of imipramine, detomidine, and oxytocin. Regardless of the protocol used, a quiet environment with minimal disturbance is associated with a better outcome. In contrast to the body of literature available on pharmacologically induced ex copula ejaculation in horses, only a few studies have been published so far on this topic in donkeys. Further studies are warranted to investigate whether pharmacologically induced ex copula ejaculation is an effective method of semen collection in jacks and to compare different pharmacological protocols for inducing ejaculation in jacks.

Kinematic Patterns in Horses Sedated With Low Doses of Detomidine: An Accelerometric Evaluation.

Alpha-2-adrenergic drugs, such as detomidine, are commonly used to sedate lame horses during examination. However, the use of these drugs should be minimized, as they have numerous side-effects, like ataxia. Therefore, we wanted to test the effects, on the locomotor pattern, of low doses of detomidine (0.003 mg/kg). Six horses were sedated with 0.003 mg/kg of detomidine and compared with the same horses administered a saline solution. Using a triaxial accelerometer, data of kinetic, coordination and energetic locomotor parameters and the degree of sedation were collected. The effects were monitored for 60 minutes after treatment administration. No effects on coordination parameters were observed, but some kinetic and energetic parameters were significantly altered after detomidine administration compared to the saline group. These results show that administering low doses of detomidine to lame horses can be a useful sedative solution, ensuring a safe examination with lower side-effects.

Analgesic Effect of Butorphanol during Castration in Donkeys under Total Intravenous Anaesthesia.

Pain management is necessary for all surgical procedures. Little scientific evidence about drug efficacy in donkeys is available. The aim of this study was to evaluate the analgesic effect of butorphanol in donkeys undergoing orchiectomy under total intravenous anaesthesia with guaifenesin-ketamine-detomidine. A randomized blinded prospective clinical trial (Protocol n. 2021/0000338), was carried out on 18 clinically healthy donkeys undergoing bilateral orchiectomy. Patients were assigned to Group D (n = 8) or Group DB (n = 10) if receiving intravenous detomidine or detomidine-butorphanol respectively, before induction of general anaesthesia with ketamine-diazepam. Intraoperative muscle relaxation, nystagmus, palpebral reflex, heart and respiratory rate, and non-invasive blood pressure were evaluated every 2 min; time to prepare the patient, duration of surgery and anaesthesia and recovery score were recorded. Group D had significantly longer surgical time, higher heart rate, higher systolic and mean blood pressure (p < 0.05; repeated measure ANOVA), increased muscle rigidity and expression of palpebral reflex (p < 0.05; Mann-Whitney U test) than group DB. Top-ups with thiopental were statistically higher in Group D. Butorphanol and detomidine together produced a more stable anaesthetic plan. The low dosage of opioid and alpha-2-agonists and reduced rescue anaesthesia are responsible for a safer and more superficial anaesthesia, which is mandatory under field conditions.

Evaluation of intramuscular anesthetic protocols in healthy domestic horses.

OBJECTIVE: To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. STUDY DESIGN: Randomized, blinded, three-way crossover prospective design. ANIMALS: A total of eight healthy adult horses weighing 470-575 kg. METHODS: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg-1), ketamine (1 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TKD); ketamine (3 mg kg-1) and detomidine (0.04 mg kg-1) (treatment KD); and tiletamine-zolazepam (2.4 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings-Mack test. A p value <0.05 was considered statistically significant. RESULTS: All horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO2 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: In domestic horses, IM injections of tiletamine-zolazepam-detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine-detomidine and tiletamine-zolazepam-ketamine-detomidine. Recoveries were comparable among protocols.

Development, Validation, and Reliability of a Sedation Scale in Horses (EquiSed).

The lack of standardization of sedation scales in horses limits the reproducibility between different studies. This prospective, randomized, blinded, horizontal and controlled trial aimed to validate a scale for sedation in horses (EquiSed). Seven horses were treated with intravenous detomidine in low/high doses alone (DL 2.5 µg/kg + 6.25 µg/kg/h; DH 5 µg/kg +12.5 µg/kg/h) or associated with methadone (DLM and DHM, 0.2 mg/kg + 0.05 mg/kg/h) and with low (ACPL 0.02 mg/kg) or high (ACPH 0.09 mg/kg) doses of acepromazine alone. Horses were filmed at (i) baseline (ii) peak, (iii) intermediate, and (iv) end of sedation immediately before auditory, visual and pressure stimuli were applied and postural instability evaluated for another study. Videos were randomized and blindly evaluated by four evaluators in two phases with 1-month interval. Intra- and interobserver reliability of the sum of EquiSed (Intraclass correlation coefficient) ranged between 0.84-0.94 and 0.45-0.88, respectively. The criterion validity was endorsed by the high Spearman correlation between the EquiSed and visual analog (0.77), numerical rating (0.76), and simple descriptive scales (0.70), and average correlation with head height above the ground (HHAG) (-0.52). The Friedman test confirmed the EquiSed responsiveness over time. The principal component analysis showed that all items of the scale had a load factor ≥ 0.50. The item-total Spearman correlation for all items ranged from 0.3 to 0.5, and the internal consistency was good (Cronbach's α = 0.73). The area under the curve of EquiSed HHAG as a predictive diagnostic measure was 0.88. The sensitivity of the EquiSed calculated according to the cut-off point (score 7 of the sum of the EquiSed) determined by the receiver operating characteristic curve, was 96% and specificity was 83%. EquiSed has good intra- and interobserver reliabilities and is valid to evaluate tranquilization and sedation in horses.

The effects of an alpha-2-adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses.

Alpha-2-adrenoceptor agonists are sedatives that can cause fluctuations in serum insulin and blood glucose (BG) concentrations in horses. The objectives of this study were to investigate the effects of detomidine and vatinoxan on BG, insulin, and glucagon concentrations in horses with and without insulin dysregulation (ID). In a blinded cross-over design, eight horses with ID and eight horses without ID were assigned to each of four treatments: detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), detomidine + vatinoxan (DET + VAT), and saline control (SAL). Blood samples were taken at 0, 1, 2, 4, 6, and 8 h. Change from baseline was used as the response in modelling, and the differences between treatments were evaluated with repeated measures analysis of covariance. P values ≤0.05 were considered significant. Comparing DET vs. SAL and DET vs. DET + VAT, insulin was higher at 2 h in the non-ID group and 2 and 4 h in the ID group. There was no difference in insulin between SAL and DET + VAT or VAT. Comparing DET vs. SAL, BG was higher at 1 and 2 h then was lower at 4 h in both ID and non-ID groups. At 1 h in both groups, BG after DET + VAT was lower than after DET but higher than after SAL. Comparing DET vs. SAL, glucagon was lower at 1 h in the ID group and 1 and 2 h in the non-ID group. Vatinoxan was effective in preventing detomidine-induced hyperglycaemia as well as the subsequent insulin increase in horses with ID.

Plasma prolactin, thyroid-stimulating hormone, melanocyte-stimulating hormone, and adrenocorticotropin responses to thyrotropin-releasing hormone in mares treated with detomidine and butorphanol.

Stress or excitement is a concern when performing endocrine tests on fractious horses. Sedation may be a solution; however, perturbation of test results may preclude useful information. Thyrotropin-releasing hormone (TRH) is a known stimulator of prolactin, thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH), and ACTH. Thyrotropin-releasing hormone-induced ACTH is a diagnostic tool for the assessment of endocrinopathies such as pituitary pars intermedia dysfunction. It is unknown if drugs commonly used for sedation alter endocrine responses. The objective of this study was to assess the effects of detomidine (DET) and butorphanol on endocrine responses to TRH. Nine light horse mares were used in a replicated 3 × 3 Latin square with the following treatments: saline, DET, and detomidine + butorphanol (DET/BUT), all administered intravenously at 0.01 mg/kg BW. A 1-wk washout period was allowed between phases, all of which were performed in December. Blood samples were collected at -10 and 0 min before treatment and 5 and 10 min post-treatment. Administration of 1 mg TRH occurred 10 min post-treatment, and blood sampling continued 5, 10, 20, and 30 min post-TRH. Data were analyzed by ANOVA as a replicated Latin square with repeated sampling. Plasma prolactin increased (P < 0.0001) after TRH in all groups, rapidly peaking at 5 min in drug-treated mares and 40 min in saline-treated mares. The peak prolactin response to TRH was 2-fold higher (P < 0.0001) in saline-treated mares compared with those drug-treated. A peak rise in plasma TSH was observed in DET/BUT-treated mares 10 min after TSH and was greater (P ≤ 0.007) compared with DET- and saline-treated mares. Plasma MSH was stimulated (P = 0.001) by DET and DET/BUT before TRH, and the peak MSH response to TRH was greater (P < 0.0001) in drug-treated mares, although not hastened as observed with prolactin and TSH. A peak rise in ACTH was observed in drug-treated mares 5 min after administration of TRH, whereas a peak rise was observed in control mares 10 min post-TRH and was almost 2-fold lower (P = 0.05) than the peak observed in DET and DET/BUT-treated mares. Basal ACTH concentrations were not affected by DET or DET/BUT, indicating that sedation with these compounds may be achieved when needing to measure basal plasma ACTH. Treatment with DET and DET/BUT did alter the prolactin, TSH, MSH, and ACTH responses to TRH; therefore, the use of these drugs may not be advisable when assessing endocrine responses to TRH stimulation.

Use of Detomidine Oromucosal Gel for Alleviation of Acute Anxiety and Fear in Horses: A Pilot Study.

The aim of this randomized, double-blind, placebo-controlled, parallel group clinical field study was to evaluate the effect of detomidine oromucosal gel in alleviating anxiety and fear in horses. Sixteen horses with a history of acute anxiety and fear associated with firework-related noise entered the study. On New Year's Eve, eight horses were treated with 30 µg/kg detomidine gel and eight horses with placebo gel. When fireworks were present, 75% (6/8) of the detomidine-treated horses were scored by their owners as having a good or excellent treatment effect on anxiety and fear, while 50% (3/6) of horses receiving placebo were scored to have a good effect. Horses' behavior was video-recorded and assessed with a focal animal continuous method by a treatment-blind expert observer. Results showed that when fireworks were present, walking behavior decreased significantly (p < 0.05) after treatment with detomidine and that horses of the placebo group, overall, showed more restlessness, vocalization, and signs of colic (Wilcoxon matched-pairs test on the first PC, p = 0.007). This study indicates that detomidine oromucosal gel can be used to alleviate acute noise-related anxiety and fear in horses, but larger treatment groups are needed to confirm the results.

Recovery Quality After Romifidine Versus Detomidine Infusion During Isoflurane Anesthesia in Horses.

To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80-120 µg kg-1 IV], anesthetic maintenance (40 µg kg-1 hour-1 IV), and recovery (20 µg kg-1 IV) or detomidine (group D), at doses of 10-20 µg kg-1 IV, 5 µg kg-1 hour-1 IV, and 2.5 µg kg-1 IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and final recovery score (FS) were compared between groups using a Mann-Whitney U-test, independent t-test, or chi-squared test, as appropriate (alpha 0.05). Parametric data are represented as the mean ± standard deviation, and nonparametric data as the median (interquartile range). Compared with group D (25 horses), horses in group R (53 horses) needed significantly fewer attempts to achieve sternal recumbency [R 1 (1-1) vs. D 1 (1-2)], remained significantly longer in sternal recumbency [R 10 (3-14,5) vs. D 5 (1-9,5) minutes], needed significantly less attempts to stand [R 1 (1-1) vs. D 2 (1-4)], and a significantly shorter time to stand after making their first attempt [R 0 (0-0) vs. D 3 (0-6) minutes], with significantly better scores for TrSta, BC, and FS in group R. The results suggest that, at the doses used, romifidine provides a better recovery quality.

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel in alpacas.

OBJECTIVES: To evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine. STUDY DESIGN: Randomized, crossover, blinded experiment. ANIMALS: A group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg). METHODS: Alpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 µg kg-1; treatment DET-IV) or detomidine gel (200 µg kg-1; treatment DET-VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography-tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant. RESULTS: Onset of sedation was faster in treatment DET-IV (1.6 ± 0.2 minutes) than in treatment DET-VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET-IV (8.3 ± 1.3 minutes) than in treatment DET-VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET-IV and DET-VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET-VAG were 39.6 ng mL-1, 19.9 minutes and 20%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.

Clinical effects of two doses of butorphanol with detomidine for intravenous premedication of healthy warmblood horses.

OBJECTIVE: To compare the effects of two different doses of butorphanol combined with detomidine administered intravenously (IV) on quality of sedation, degree of ataxia and anaesthetic induction in horses. STUDY DESIGN: Randomized, blinded, clinical study. ANIMALS: A total of 40 client-owned healthy warmblood horses scheduled for elective surgery under general anaesthesia. METHODS: Horses were randomly allocated to be administered 8 µg kg-1 detomidine IV plus either 20 or 50 µg kg-1 butorphanol IV, with the principal investigator blinded to group allocation. Head height was measured before drug injection and 2 minutes thereafter. Data were compared using unpaired t test. Horses were filmed and scored using Simple Descriptive Scales for sedation (2 and 15 minutes after IV injection), ataxia (at walk, immediately after the 2 minute time point) and quality of swing-door induction following diazepam and ketamine administration. Data are shown as median (and range where appropriate). Scores were compared using chi-square tests (p < 0.05). RESULTS: There were 14 and 17 horses in high-dose (HD) and low-dose (LD) groups respectively. Data from nine horses were excluded. Mean head height reduction did not differ between groups (p = 0.86), nor did sedation scores at 2 minutes (median = 3 in both groups; p = 0.09) or 15 minutes (median = 2 in both groups; p = 0.63). There was no significant difference in the requirement for additional detomidine (p = 0.73) or in induction quality between groups (p = 0.99), but initial ataxia was significantly greater in the HD group 2 (1-3) versus 2.5 (1-3) in the LD group (p = 0.017). CONCLUSIONS AND CLINICAL RELEVANCE: In healthy warmblood horses, simultaneous administration of 50 rather than 20 µg kg-1 butorphanol with 8 µg kg-1 detomidine does not provide greater sedation or affect induction, but it causes more pronounced ataxia shortly after IV injection.