OBJECTIVE To assess the effects of sedation on results of acoustoelastography of the superficial digital flexor tendons (SDFTs) in clinically normal horses. ANIMALS 27 clinically normal horses. PROCEDURES For each horse, the pathology index (PI) for the SDFT of each thoracic limb was determined by use of acoustoelastography at 4 locations (5, 10, 15, and 20 cm distal to the accessory carpal bone). Horses were evaluated before and after they were sedated with a combination of detomidine hydrochloride (0.01 mg/kg, IV) and butorphanol tartrate (0.01 mg/kg, IV). A repeated-measures ANOVA was used for statistical analysis. RESULTS Overall, the PI was lower after sedation than before sedation. In addition, the PI was lower at more distal locations than at more proximal locations. There was not a significant effect of limb (left or right). Differences among individual horses accounted for the largest variance effect. CONCLUSIONS AND CLINICAL RELEVANCE Sedation with detomidine and butorphanol facilitated acoustoelastography; however, it decreased the SDFT PI in clinically normal horses and should be used consistently in prospective studies. Variance associated with each individual horse in the sample population had the greatest effect on the PI.

OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. ANIMALS 12 healthy adult dogs.PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m2) or OTM (1 mg/m2) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m2) or detomidine gel by OTM administration (0.5 mg/m2), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

Objective-To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. Animals-6 healthy horses. Procedures-Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used for gait assessment 15 minutes before and 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each treatment. Eight variables were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power, and total power; the force of acceleration and 3 components of power were then calculated. Results-Significant differences were evident in stride frequency and regularity between treatments with saline solution and each α2-adrenoceptor agonist drug; in speed, dorsoventral power, propulsive power, total power, and force values between treatments with saline solution and detomidine or romifidine; and in mediolateral power between treatments with saline solution and detomidine. Stride length did not differ among treatments. Conclusions and Clinical Relevance-Accelerometric evaluation of horses administered α2-adrenoceptor agonist drugs revealed more prolonged sedative effects of romifidine, compared with effects of xylazine or detomidine. Accelerometry could be useful in assessing the effects of other sedatives and analgesics. Accelerometric data may be helpful in drug selection for situations in which a horse's balance and coordination are important.

The aim of this study was to determine the viability and cardiorespiratory effects of the association of epidural alpha-2 adrenergic agonists and lidocaine for ovariohysterectomy (OH) in bitches. Forty-two bitches were spayed under epidural anesthesia with 2.5 mg/kg body weight (BW) of 1% lidocaine with adrenaline (CON) or in association with 0.25 mg/kg BW of xylazine (XYL), 10 μg/kg BW of romifidine (ROM), 30 μg/kg BW of detomidine (DET), 2 μg/kg BW of dexmedetomidine (DEX), or 5 μg/kg BW of clonidine (CLO). Heart rate (HR), respiratory rate (fR) and arterial pressures were monitored immediately before and every 10 min after the epidural procedure. Blood gas and pH analysis were done before, and at 30 and 60 min after the epidural procedure. Animals were submitted to isoflurane anesthesia if they presented a slightest sign of discomfort during the procedure. Time of sensory epidural block and postoperative analgesia were evaluated. All animals in CON and DEX, 5 animals in ROM and CLO, 4 animals in XYL, and 3 in DET required supplementary isoflurane. All groups, except CLO, showed a decrease in HR. There was an increase in arterial pressures in all groups. Postoperative analgesia lasted the longest in XYL. None of the protocols were totally efficient to perform the complete procedure of OH; however, xylazine provided longer postoperative analgesia than the others.

Objective-To compare effects of oxytocin, acepromazine maleate, xylazine hydrochloride-butorphanol tartrate, guaifenesin, and detomidine hydrochloride on esophageal manometric pressure in horses. Animals-8 healthy adult horses. Procedure-A nasogastric tube, modified with 3 polyethylene tubes that exited at the postpharyngeal area, thoracic inlet, and distal portion of the esophagus, was fitted for each horse. Amplitude, duration, and rate of propagation of pressure waveforms induced by swallows were measured at 5, 10, 20, 30, and 40 minutes after administration of oxytocin, detomidine, acepromazine, xylazine-butorphanol, guaifenesin, or saline (0.9% NaCl) solution. Number of spontaneous swallows, spontaneous events (contractions that occurred in the absence of a swallow stimulus), and high-pressure events (sustained increases in baseline pressure of > 10 mm Hg) were compared before and after drug administration. Results-At 5 minutes after administration, detomidine increased waveform amplitude and decreased waveform duration at the thoracic inlet. At 10 minutes after administration, detomidine increased waveform duration at the thoracic inlet. Acepromazine administration increased the number of spontaneous events at the thoracic inlet and distal portion of the esophagus. Acepromazine and detomidine administration increased the number of high-pressure events at the thoracic inlet. Guaifenesin administration increased the number of spontaneous events at the thoracic inlet. Xylazine-butorphanol, detomidine, acepromazine, and guaifenesin administration decreased the number of spontaneous swallows. Conclusions and Clinical Relevance-Detomidine, acepromazine, and a combination of xylazine butorphanol had the greatest effect on esophageal motility when evaluated manometrically. Reduction in spontaneous swallowing and changes in normal, coordinated peristaltic activity are the most clinically relevant effects.

The aim of this study was to determine the efficacy of a concentrated combination of tiletamine-zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53 mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free-range cattle for clinical procedures. The combination was administered intramuscularly to 53 animals. Anesthesia was reversed with the α2-adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with lidocaine when required. The TZKD combination induced suitable immobilization for minor surgical procedures or medical treatments. Anesthetic onset was rapid, taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of anesthesia depended on the time of administration of the antagonist; the animals recovered in the standing position in 12.9 ± 8.9 min after the administration of atipamezole. The quality of anesthesia and analgesia were satisfactory. In conclusion, this TZKD combination can be used for both immobilization and minor surgical procedures in free-range cattle.

Objective—To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. Animals—12 adult racehorses. Procedures—Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography–mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration. Results—Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration. Conclusions and Clinical Relevance—A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively should be adopted for sublingual administration of detomidine gel.

We compared the anesthetic combination of detomidine, ketamine, and halothane in control horses not undergoing apparently painful procedures with that in horses during arthroscopic surgery. The effectiveness of this regimen in suppressing neurologic response to surgery was, thus, evaluated. In this study, significant differences were not observed in electroencephalographic total amplitude, spectral edge, or beta-to-delta frequency ratio between surgically treated and nonsurgically treated (control) horses. On the basis of its attenuation of encephalographic responses, we conclude that detomidine (20 microgram/kg of body weight, IV) and ketamine (2.2 mg/kg, IV) induction of anesthesia followed by maintenance with halothane is an effective regimen for control of pain in horses during arthroscopic surgery. The insignificant frequency changes observed without any other signs of inadequate anesthesia or pain may indicate a surgical stress response. We hypothesize that brain activity monitoring may give an earlier index to initiation of surgically induced stress than do hormonal responses, because endocrine alterations are not as rapidly perceived as is the electroencephalogram. Analysis of spectral edge frequency changes could be used to evaluate anesthetic regimens to find those that cause the least stress to the CNS during surgery in horses. Differences in species responses to an anesthetic agent or the regimen's effectiveness in prevention of pain during surgery may be identified by adoption of the study model. Evaluation of cardiopulmonary variables during anesthesia, with and without surgery, did not reveal any alterations that would be relevant to CNS responses. Blood pressure, heart rate, PAO2, PACO2 and pH were stabilized by use of intermittent positive-pressure ventilation in all horses, and dobutamine was administered as needed, to avoid bias of electroencephalogram data.

Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1 (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of body weight-1.min-1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart rate = -4.7 [log(e) detomidine concentration] + 44.3, P < 0.01; cardiac index = -10.5 [log(e) detomidine concentration] + 73.6, P < 0.01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arterial blood pressure increased significantly from 118 +/- 11 mm of Hg at baseline to 146 +/- 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemic vascular resistance (baseline, 182 +/- 28 mm of Hg.ml-1.min-1.kg-1) increased significantly during infusions 3 and 4 (to 294 +/- 79 and 380 +/- 58, respectively). Plasma atrial natriuretic peptide concentration was significantly increased with increasing detomidine concentration (20.4 +/- 3.8 pg/ml at baseline to 33.5 +/- 9.1 at infusion 4). There were few significant changes in respiration rate and arterial blood gas and pH values. We conclude that maintenance of steady-state detomidine plasma concentrations resulted in cardiopulmonary changes that were quantitatively similar to those induced by detomidine bolus administration in horses.

OBJECTIVE To evaluate hemodynamic, respiratory, and sedative effects of buccally administered detomidine gel and reversal with atipamezole in dogs. ANIMALS 8 adult purpose-bred dogs. PROCEDURES Arterial and venous catheters were placed. Baseline heart rate, respiratory rate, cardiac output (determined via lithium dilution with pulse contour analysis), oxygen delivery, systemic vascular resistance, arterial blood gas values, and sedation score were obtained. Detomidine gel (2.0 mg/m2) was administered on the buccal mucosa. Cardiopulmonary data and sedation scores were obtained at predetermined times over 180 minutes. Atipamezole (0.1 mg/kg) was administered IM at 150 minutes. Reversal of sedation was timed and scored. Data were analyzed with an ANOVA. RESULTS Compared with baseline values, heart rate was lower at 45 to 150 minutes, cardiac output and oxygen delivery were lower at 30 to 150 minutes, and systemic vascular resistance was increased at 30 to 150 minutes. There were no significant changes in Paco2, Pao2, or lactate concentration at any time point, compared with baseline values, except for lactate concentration at 180 minutes. All dogs became sedated; maximum sedation was detected 75 minutes after administration of detomidine. Mean ± SD time to recovery after atipamezole administration was 7.55 ± 1.89 minutes; sedation was completely reversed in all dogs. No adverse events were detected. CONCLUSIONS AND CLINICAL RELEVANCE Buccally administered detomidine gel was associated with reliable and reversible sedation in dogs, with hemodynamic effects similar to those induced by other α2-adrenoceptor agonists. Buccally administered detomidine gel could be an alternative to injectable sedatives in healthy dogs.