Cardiovascular effects of medetomidine, detomidine and xylazine in horses

The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine. KEY WORDS: cardiovascular effect, detomidine, equine, medetomidine, xylazine.     

Clinical comparison of dexmedetomidine and medetomidine for isoflurane balanced anaesthesia in horses

Objective

To compare the effects of two balanced anaesthetic protocols (isoflurane–dexmedetomidine versus medetomidine) on sedation, cardiopulmonary function and recovery in horses.

Comparison of the sedative effects of medetomidine and xylazine in horses.

The sedative effects in horses of the new alpha 2 agonist medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of medetomidine (5 micrograms/kg bodyweight and 10 micrograms/kg bodyweight) and with one dose of xylazine (1 mg/kg bodyweight) given by intravenous injection. Medetomidine at 10 micrograms/kg was similar to 1 mg/kg xylazine in its sedative effect but produced more severe and more prolonged ataxia, and one animal fell over during the study. Medetomidine at 5 micrograms/kg produced less sedation but a similar degree of ataxia to 1 mg/kg xylazine.     

Cardiopulmonary and sedative effects of intravenous administration of low doses of medetomidine and xylazine to adult horses

OBJECTIVE: To determine the cardiopulmonary and sedative effects of medetomidine hydrochloride in adult horses and to compare those effects with effects of an equipotent dose of xylazine hydrochloride. ANIMALS: 10 healthy adult female horses. PROCEDURE: 5 horses were given medetomidine (4 microg/kg of body weight, i.v.), and the other 5 were given xylazine (0.4 mg/kg, i.v.). Heart rate, respiratory rate, arterial blood pressures, pulmonary arterial blood pressures, and cardiac output were recorded, and sedation and ataxia scores were assigned before and every 5 minutes after drug administration for 60 minutes. Rectal temperature and blood gas partial pressures were measured every 15 minutes after drug administration. RESULTS: Arterial blood pressure was significantly decreased throughout the study among horses given medetomidine and was significantly decreased for 40 minutes among horses given xylazine. Compared with baseline values, cardiac output was significantly decreased 10, 20, and 40 minutes after administration of medetomidine and significantly increased 40 and 60 minutes after administration of xylazine. Despite the significant decrease in respiratory rate in both groups, results of blood gas analyses were not significantly changed over time. Ataxia and sedation scores were of similar magnitude for the 2 groups, but ataxia persisted slightly longer among horses given medetomidine. Horses resumed eating hay 10 to 55 minutes after drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that equipotent low doses of medetomidine and xylazine induce comparable levels of ataxia and sedation and similar cardiopulmonary changes in adult horses.     

A comparison of the haemodynamic effects of epidurally administered medetomidine and xylazine in dogs

Alpha₂ agonists have a significant role in epidural anaesthetic techniques. However, there are few reports regarding epidural administration of these drugs especially in small animals ( Greene et al. 1995; Keegan et al. 1995; Vesal et al. 1996 ). This study compared the haemodynamic effects of xylazine and medetomidine after epidural injection in dogs. Six dogs (four females and two males) weighing 27.5 ± 3.39 kg, aged 5.6 ± 1.42 years were studied on two separate occasions one month apart. Dogs were sedated with 0.5 mg kg^?1 diazepam IM and 0.1 mg kg^?1 acepromazine IM. After 20 minutes, a lumbosacral epidural injection of 0.25 mg kg^?1 xylazine was administered (group X). One month later, following the same sedation, 15 µg kg^?1 medetomidine was administered epidurally (group M). Haemodynamic variables (ECG and indirect blood pressure (Doppler)), respiratory rate and rectal temperature were recorded before (baseline) and then every 5 minutes after the epidural injection, up to 60 minutes. Differences between groups were compared by a paired t‐test. Within group changes were compared to basal values by anova . A p‐value of < 0.05 was considered statistically significant. Both groups showed significant reductions in heart rate (106.3 ± 7.7 beats minute^?1 baseline versus 67.7 ± 7.6 (group M); 91 ± 3.8 baseline versus 52.3 ± 9 (group X)) and mean arterial blood pressure (113.1 ± 12.3 mm Hg baseline versus 87 ± 11 (group M); 118 ± 7 baseline versus 91 ± 14 (group X)). There were no differences between groups in these variables. After epidural injection, first degree atrioventricular block was recorded significantly more often in group X (50% against 33%) but second degree block was significantly more frequent in group M (66% against 33%). Also 50% of dogs in group X and 66% in group M showed sinus arrest. Respiratory rate decreased significantly in both groups following the epidural injection (20.66 ± 0.66 minute^?1 baseline versus 16.33 ± 4.77 (group M); 37.66 ± 0.56 baseline versus 16.33 ± 1.81 group X), but no differences between groups were observed. Rectal temperature decreased significantly in group X (38.16 ± 0.21) with respect to the basal measurement (39.30 ± 0.14 °C). In group M, there was no significant reduction in temperature, however, no statistical difference in rectal temperature was found between groups. This study shows that 0.25 mg kg^?1 xylazine and 15 µg kg^?1 medetomidine produce similar, significant cardiovascular and respiratory changes following lumbosacral epidural administration in dogs.     

Hyoscine‐N‐butylbromide premedication on cardiovascular variables of horses sedated with medetomidine

ObjectiveTo evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses.Study designRandomized, crossover experimental study.AnimalsEight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years.MethodsBaseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2^oAV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO₂) and oxygen (PaO₂) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg^?1; group HIV), IM hyoscine (0.3 mg kg^?1; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg^?1) was administered IV and measurements were recorded at various time points for 130 minutes.ResultsMedetomidine induced bradycardia, 2^oAV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2^oAV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute^?1 and 241 ± 37 mmHg versus 65 ± 16 beats minute^?1 and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO₂ and PaO₂ were not significantly changed by administration of medetomidine with or without hyoscine.Conclusion and clinical relevanceHyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.     

Radioreceptor assay for determination of xylazine and medetomidine in sheep plasma

A radioreceptor assay technique is described for the measurement of xylazine and medetomidine in sheep plasma. The assay was based on the displacement of tritiated clonidine from a 2-adrenoceptors in a rat brain homogenate by xylazine or medetomidine extracted from plasma. Plasma samples from sheep which had been given xylazine and medetomidine were treated with alumina to remove endogenous catecholamines which would otherwise have bound to α₂-_- adrenoceptors and interfered with the assay. The drugs were then extracted using chloroform, reconstituted in buffer and used to displace [³H]clonidine. The concentration of α₂-agonist was calculated by reference to standard curves. The method had a detection limit of 2.5 ng/mL for xylazine and 0.24 ng/mL for medetomidine. The assay could also be used to detect metabolites capable of binding to α₂-receptors.     

The minimum infusion rate (MIR) of propofol for total intravenous anesthesia after premedication with xylazine in horses

To investigate an adequate infusion rate of propofol for total intravenous anesthesia (TIVA) in horses, the minimum infusion rate (MIR) comparable to the minimum alveolar anesthetic concentration (MAC) of inhalation anesthetic was determined under constant ventilation condition by intermittent positive pressure ventilation (IPPV). In addition, arterial propofol concentration was measured to determine the concentration corresponding to the MIR (concentration preventing reaction to stimulus in 50% of population, Cp(50)). Further, 95% effective dose (ED(95)) was estimated as infusion rate for acquiring adequate anesthetic depth. Anesthetic depth was judged by the gross purposeful movement response to painful stimulus. MIR and Cp(50) were 0.10 +/- 0.02 mg/kg/min and 5.3 +/- 1.4 microg/ml, respectively. ED(95) was estimated as 0.14 mg/kg/min (1.4MIR).     

Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes

α₂-Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the α₂-adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four α₂-adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of a₂-adrenergic receptor. The K_D for the α₂-adrenergic receptor radioligand, [³H]-MK-912, in HT29 cells (α_2A-), neonatal rat lung (α_2B-), OK cells (α_2C-) and PC12 cells transfected with RG20 (α_2D-) were 0.38 ± 0.08 n m , 0.70 ± 0.5 n m , 0.07 ± 0.02 n m and 0.87 ± 0.03 n m , respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the α₂-adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the α₂-adrenergic receptor subtypes. These data suggest that available sedative/hypnotic α₂-adrenergic receptor agonists can not discriminate between the four known α₂-adrenergic receptor subtypes.     

Echocardiographic evaluation of the effects of medetomidine and xylazine in dogs

The echocardiographic effects of medetomidine and xylazine were evaluated in 6 healthy dogs. Values for echocardiographic variables were significantly different from pre-treatment values after administration of both drugs. The effects of medetomidine were similar to that of xylazine. Because of their cardiac depressant effects, both drugs should be used with care in sick dogs.     

A clinical comparison of two anaesthetic protocols using lidocaine or medetomidine in horses

OBJECTIVE: To compare the effects of two balanced anaesthetic protocols on end-tidal isoflurane (Fe'ISO), cardiopulmonary performance and quality of recovery in horses. DESIGN: Prospective blinded randomized clinical study. ANIMALS: Sixty-nine client-owned horses, American Society of Anesthesiologists category I and II, undergoing elective surgery. METHODS: The horses were premedicated with acepromazine (0.03 mg kg(-1)) IM 30-60 minutes before induction of anaesthesia and were randomly assigned to one of two treatments: in group L (37 horses) xylazine (1 mg kg(-1)) and in group M (31 horses) medetomidine (7 microg kg(-1)) was administered IV for sedation. Anaesthesia was induced 5 minutes later with ketamine (2.2 mg kg(-1)) and diazepam (0.02 mg kg(-1)) IV and maintained with isoflurane in oxygen/air (initial FIO2 0.40-0.50) and a constant rate infusion (CRI) of either lidocaine (2 mg kg(-1)/15 minutes loading dose followed by 50 microg kg(-1) minute(-1)) (group L) or medetomidine (3.5 microg kg(-1) hour(-1)) (group M). If horses showed movement or nystagmus, additional thiopental or ketamine was administered. Heart rate, mean arterial pressure (MAP), Fe'ISO and arterial blood gases were measured. Cardiac output was measured with the lithium dilution method in 10 (group L) and 11 (group M) horses every 45 minutes. Recovery was scored. RESULTS: Heart rate and the cardiac index (CI) were significantly higher in group L with changes over time. In group M, MAP was significantly higher during the first 50 minutes. Group L needed more additional ketamine and thiopental to maintain a surgical plane of anaesthesia and Fe'ISO was significantly higher from 70 minutes. Recovery was longer in group M and of better quality. The significance level was set at p < 0.05. CONCLUSIONS AND CLINICAL RELEVANCE: In group M, maintenance of stable anaesthetic depth was easier and lower Fe'ISO was required to maintain a surgical plane of anaesthesia. Recoveries were longer but of better quality. The CI was higher in group L but cardiovascular function was generally well maintained in both groups.     

Disposition of propofol after medetomidine premedication in beagle dogs

Propofol by infusion was administered to 6 adult beagle dogs on 2 separate occasions. The dogs received either no premedication or 20 μg/kg im medetomidine 15 min before induction of anaesthesia, with propofol given at 7 mg/kg/min to permit tracheal intubation. After tracheal intubation the infusion rate was maintained for 120 min at 0.4 mg/kg/min in the non-premedicated, and 0.2 mg/kg/min in the premedicated dogs. The latter group received atipamezole 50 μg/kg im immediately at the end of the infusion. After induction of anaesthesia, a 7F balloon catheter designed for thermal dilution measurement of cardiac output was inserted via the right jugular vein. Blood propofol concentrations were measured by HPLC with fluorescence detection and kinetic variables calculated using non-compartmental moment analysis. The induction dose of propofol was 7.00 (sem 0.55) mg/kg in non-premedicated compared with 3.09 (0.25) mg/kg in premedicated dogs. There were differences in systemic clearance and mean residence time (MRT_iv); 47.5 (6.2) ml/kg/min vs 29.0 (4.4) ml/kg/min (non-premedicated vs premedicated) and 132.3 (5.2) min vs 152.4 (3.1) min (P < 0.02 and P < 0.001, respectively). Cardiorespiratory effects were similar in the 2 groups although heart rate was lower in the premedicated dogs. Venous admixture was high (20–45%) but similar in the 2 groups.     

Dexmedetomidine or medetomidine premedication before propofol-desflurane anaesthesia in dogs

The objective of this study was to evaluate dexmedetomidine as a premedicant in dogs prior to propofol-desflurane anaesthesia, and to compare it with medetomidine. Six healthy dogs were anaesthetized. Each dog received intravenously (i.v.) five preanaesthetic protocols: D1 (dexmedetomidine, 1 microg/kg, i.v.), D2 (dexmedetomidine, 2 microg/kg, i.v.), M1 (medetomidine, 1 microg/kg, i.v.), M2 (medetomidine, 2 microg/kg, i.v.), or M4 (medetomidine, 4 microg/kg, i.v.). Anaesthesia was induced with propofol (2.3-3.3 mg/kg) and maintained with desflurane. The following variables were studied: heart rate (HR), mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, respiratory rate (RR), arterial oxygen saturation, end-tidal CO2, end-tidal concentration of desflurane (EtDES) required for maintenance of anaesthesia and tidal volume. Arterial blood pH (pHa) and arterial blood gas tensions (PaO2, PaCO2) were measured during anaesthesia. Time to extubation, time to sternal recumbency and time to standing were also recorded. HR and RR decreased significantly during sedation in all protocols. Cardiorespiratory variables during anaesthesia were statistically similar for all protocols. EtDES was significantly different between D1 (8.1%) and D2 (7.5%), and between all doses of medetomidine. Desflurane requirements were similar for D1 and M2, and for D2 and M4 protocols. No statistical differences were observed in recovery times. The combination of dexmedetomidine, propofol and desflurane appears to be effective for induction and maintenance of general anaesthesia in healthy dogs.     

Epidural injection of xylazine for perineal analgesia in horses

Local anesthetics given in the epidural space of a horse may cause hind limb weakness in addition to analgesia. Because alpha 2 agonists given by epidural injection cause sensory blockade without motor effects in human beings and other species, their use in veterinary anesthesia is appealing. This study was designed to examine the effectiveness of xylazine HCl, an alpha 2 agonist commonly used in horses. Xylazine, 0.9% NaCl, and lidocaine were given by epidural injection to horses subjected to perineal electrical stimulation. Administration of xylazine (0.17 mg/kg of body weight, diluted to a 10-ml volume, using 0.9% NaCl) induced approximately 2.5 hours of local analgesia without apparent side effects. Higher doses of xylazine caused mild hind limb ataxia. Administration of lidocaine induced a similar duration of analgesia, with severe hind limb ataxia (100% incidence). We concluded that xylazine given by epidural injection results in safe, effective perineal analgesia in horses.     

Neurohormonal and metabolic effects of medetomidine compared with xylazine in beagle dogs

This study was aimed to investigate and compare the effects of medetomidine and xylazine on the blood level of some stress-related neurohormonal and metabolic variables in clinically normal dogs, especially focusing on time and dose relations of the effects. A total of 9 beagle dogs were used for 9 groups, which were treated with physiological saline solution (control), 10, 20, 40, and 80 μg/kg medetomidine, and 1, 2, 4, and 8 mg/kg xylazine, intramuscularly. Blood samples were taken at 10 times during 24 h from a central venous catheter. Plasma norepinephrine, epinephrine, cortisol, glucose, insulin, glucagon, and non-esterified fatty acid concentrations were determined. Both medetomidine and xylazine similarly and dose-dependently inhibited norepinephrine release and lipolysis. Medetomidine suppressed epinephrine release dose-dependently with greater potency than xylazine. Xylazine also tended to decrease epinephrine levels dose-dependently. The cortisol and glucagon levels did not change significantly in any treatment group. Both drugs suppressed insulin secretion with similar potency. Both medetomidine and xylazine increased glucose levels. The hyperglycemic effect of medetomidine, in contrast with xylazine, was not dose-dependent at the tested dosages. The results suggested that the effect of medetomidine on glucose metabolism may not be due only to α₂-adrenoceptor-mediated actions.     

Neurohormonal and metabolic effects of medetomidine compared with xylazine in healthy cats

The purpose of this study was to investigate and compare the effects of medetomidine and xylazine on some neurohormonal and metabolic variables in healthy cats. Five cats were used repeatedly in each of 11 groups, which were injected intramuscularly with physiological saline solution (control), 20, 40, 80, 160, and 320 microg/kg of medetomidine, and 0.5, 1, 2, 4, and 8 mg/kg of xylazine. Blood samples were taken over 24 h from the jugular vein for determination of plasma glucose, insulin, cortisol, epinephrine, norepinephrine, glucagon, and nonesterified fatty acid concentrations. Both medetomidine and xylazine induced remarkable hyperglycemia that was dose-dependent except for the response to medetomidine from 0 to 3 h. Both agents suppressed epinephrine and norepinephrine release but not in a dose-dependent manner at the tested dosages. Both agents inhibited insulin release and lipolysis, with similar potency, and tended to suppress cortisol release. The glucagon levels did not change significantly in any of the groups. These results suggest that the effects of medetomidine and xylazine on glucose metabolism and catecholamine release may not be due only to the actions mediated by alpha2-adrenoceptors.     

Effects of medetomidine premedication on propofol infusion anaesthesia in dogs

Observations of cardiovascular and respiratory parameters were made on six dogs anaesthetized on two separate occasions for 120 minutes with a propofol infusion, once without premedication and once following premedication with 10 μg kg-¹ of intramuscular medetomidine. During anaesthesia the heart rate and cardiac index tended to be lower following medetomidine premedication, while the mean arterial pressure was significantly greater (p<0.05). Although the differences were not statistically significant, the systemic vascular resistance, pulmonary vascular resistance and stroke volume index were also greater in dogs given medetomidine. The mean arterial oxygen and carbon dioxide tensions were similar under both regimens, but in 2 dogs supplementary oxygen had to be administered during anaesthesia to alleviate severe hypoxaemia on both occasions they were anaesthetized. Minute and tidal volumes of respiration tended to be greater in dogs not given medetomidine but medetomidine premedication appeared to have no effect on venous admixture. Dogs given medetomidine received intramuscular atipamezole at the end of the 120 min. propofol infusion; the mean time from induction of anaesthesia to walking without ataxia was 174. min in the unpremedicated dogs and 160 min. in the dogs given atipamezole. The mean blood propofol concentration at which the dogs walked without ataxia was higher in the unpremedicated animals (2.12 ± 0.077 μg. ml-¹ compared with 1.27 ± 0.518 μg. ml-¹ in the premedicated dogs). The oxygen delivery to the tissues was lower after medetomidine premedication (p = 0.03) and the oxygen consumption was generally lower after medetomidine premedication but the difference did not achieve statistical significance. No correlation could be demonstrated between blood propofol concentration and cardiac index, systemic or pulmonary vascular resistance indices, systolic, diastolic or mean arterial blood pressures.     

Cardiovascular effects of xylazine and detomidine in horses

The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.