Effects of 2 different infusion rates of medetomidine on sedation score,cardiopulmonary parameters,and serum levels of medetomidine in healthy dogs

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha₂ agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.     

The cardiopulmonary effects of clenbuterol when administered to dorsally recumbent halothane-anaesthetised ponies - failure to increase arterial oxygenation

Clenbuterol (0·8 μg kg ⁻¹ intravenously) was investigated in ponies (small horses) anaesthetised with acepromazine, detomidine and thiopentone, then halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic group). Following instrumentation, ponies were placed in dorsal recumbency for 60 minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given, and cardiopulmonary parameters monitored for a further 60 minutes. In the hyperoxic group, clenbuterol administration resulted in a transitory (<five minutes) 15 per cent fall in arterial blood pressure and 78 per cent rise in intramuscular blood flow. Heart rate increased from a mean of 42 (SD 4) to 54 (12) beats per minute, the rise being significant for 15 minutes. Cardiac index increased from 2·1 (0·7) to 3·-9 (0·7) litres m⁻² and remained significantly elevated for the remainder of the measurement period. Cardiovascular changes in the hypoxic group were similar. 30 minutes after clenbuterol administration, PaO₂ had changed non-significantly from 32·.3 (19·2) to 33·.4 (17) kPa in the hyperoxic group and from 7·9 (1·8) to 8·.6 (1·3) kPa in the hypoxic group. The study concludes that under these experimental conditions, clenbuterol does not cause significant improvement in arterial oxygenation, but its cardiovascular effects are minimal or advantageous.     

A comparison of edrophonium and neostigmine for the reversal of mivacurium-induced neuromuscular blockade in sheep

The rate of reversal of neuromuscular block was compared in 36 sheep receiving either edrophonium (500 μg kg⁻¹) and atropine (80 μg kg⁻¹), neostigmine (50 μg kg⁻¹) and atropine (80 μg kg⁻¹) or saline (10 ml), using the train of four count (TO4C) recorded at n. facialis - m. levator nasolabialis. Neuromuscular block was produced with mivacurium (200 μg kg⁻¹) followed later by a single incremental dose of 70 μg kg⁻¹. Antagonists or saline were given when spontaneous recovery from the incremental dose (T04C = 1) = 1 begun. The T04C increased from 1 to 4 in all animals, in all treatment groups within 10 minutes of reversal. The T04C was 4 in all animals five minutes after edrophonium, and seven minutes after neostigmine; differences were not statistically significant. The T04C was significantly higher with edrophonium two and three minutes after antagonism compared with saline. The data show that spontaneous recovery from mivacurium is rapid in sheep, although reversal is accelerated by anticholinesterase drugs.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats.

OBJECTIVE: To evaluate the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine hydrochloride in clinically normal cats. ANIMALS: 7 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and thermodilution catheters were placed for measurement of central venous, pulmonary, and pulmonary capillary wedge pressures and for determination of cardiac output. The dorsal pedal artery was catheterized for measurement of arterial blood pressures and blood gas tensions. Baseline variables were recorded, and medetomidine (20 microg/kg of body weight, IM) was administered. Hemodynamic measurements were repeated 15 and 30 minutes after medetomidine administration. RESULTS: Heart rate, cardiac index, stroke index, rate-pressure product, and right and left ventricular stroke work index significantly decreased from baseline after medetomidine administration, whereas systemic vascular resistance and central venous pressure increased. However, systolic, mean, and diastolic arterial pressures as well as arterial pH, and oxygen and carbon dioxide tensions were not significantly different from baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered alone to clinically normal cats, medetomidine (20 microg/kg, IM) induced a significant decrease in cardiac output, stroke volume, and heart rate. Arterial blood pressures did not increase, which may reflect a predominant central alpha2-adrenergic effect over peripheral vascular effects.     

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.     

Effects of medetomidine,l‐methadone,and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg^?1 IV), l–methadone (0.1 mg kg^?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.     

A comparison of the efficacy and cardiorespiratory effects of four medetomidine-based anaesthetic protocols in the red fox (Vulpes vulpes)

ObjectiveTo evaluate the anaesthetic and cardiorespiratory effects of four anaesthetic protocols in red foxes (Vulpes vulpes).Study designProspective, blinded and randomized complete block design.AnimalsTen adult captive red foxes.MethodsFoxes were anaesthetized by intramuscular (IM) injection using four protocols in random order: medetomidine 40 μg kg^?1, midazolam 0.3 mg kg^?1 and butorphanol 0.1 mg kg^?1 (MMiB), medetomidine 40 μg kg^?1 and ketamine 4 mg kg^?1 (MK40/4), medetomidine 60 μg kg^?1 and ketamine 4 mg kg^?1 (MK60/4), medetomidine 40 μg kg^?1 and tiletamine/zolazepam 2 mg kg^?1 (MTZ). Time to lateral recumbency, induction time and time to recovery following IM administration of atipamezole 0.2 mg kg^?1 were recorded. Heart rate (HR), respiratory rate (_fR) and rhythm, blood pressure, rectal temperature, end-tidal CO₂ tension (Pe′Co₂), functional oxygen saturation and presence/absence of interdigital, palpebral and ear reflexes were recorded every 10 minutes, and following administration of atipamezole. Data were analysed using two-way repeated-measures anova with Bonferroni post tests; p < 0.05 was considered significant.ResultsAll protocols produced profound sedation with good muscle relaxation. Only the MMiB protocol diverged significantly from the others. Induction of anaesthesia and recovery time following atipamezole were significantly longer, and f_R and initial HR significantly lower with MMiB than with the other protocols. With all protocols, mean arterial blood pressure (MAP) was initially relatively high (140–156 mmHg), and decreased significantly over time. With all protocols, the administration of atipamezole resulted in a rapid, significant decrease in MAP and an increase in HR.Conclusions and clinical relevanceAll four protocols provided anaesthetic conditions suitable for minor procedures and allowed endotracheal intubation. The cyclohexanone protocols provided quicker and more reliable inductions and recoveries than the MMiB protocol.     

Minimal alveolar concentration of desflurane in combination with an infusion of medetomidine for the anaesthesia of ponies

The minimum alveolar concentration of desflurane when combined with a continuous infusion of medetomidine at 3.5 microg/kg/hour was measured in seven ponies. Anaesthesia was induced with medetomidine (7 microg/kg intravenously) followed by ketamine (2 mg/kg intravenously) and maintained with desflurane in oxygen. The infusion of medetomidine was started 20 minutes after the induction of anaesthesia. The electrical test stimulus was applied at the coronary band (50 V, 10 ms bursts at 5 Hz for one minute), and heart rates and rhythms, arterial blood pressures, and arterial blood gas tensions were measured at intervals, just before the application of the stimulus. The mean (sd) minimum alveolar concentration of desflurane was 5.3 (1.04) per cent (range 3.2 to 6.4 per cent), 28 per cent less than the previously published value for desflurane alone after the induction of anaesthesia with xylazine and ketamine. The cardiopulmonary parameters remained stable throughout the period of anaesthesia. The mean (sd) time taken by the ponies to stand after the administration of desflurane ceased was 16.5 (6.17) (range 5.8 to 26) minutes, and the quality of recovery was good or excellent. However, one pony died shortly after standing; a postmortem examination revealed that it had chronic left atrial dilatation.     

Effects of intravenous infusions of cholecystokinin-8 and pentagastrin on plasma concentrations of insulin and glucagon in sheep

The effects of cholecystokinin-8 (cck-8) and pentagastrin on insulin and glucagon secretion were studied in conscious sheep. Intravenous infusions of ccx-8 (3 to 1000 pmol kg⁻¹ min⁻¹ for 30 minutes) induced a dose-dependent increase in plasma insulin, but did not alter plasma glucagon concentration. The threshold dose of ccx-8 for stimulation of insulin secretion was 10 to 30 pmol kg⁻¹ min⁻¹. Pentagastrin was infused intravenously at doses of 10 to 3000 pmol kg⁻¹ min⁻¹. The maximal dose of pentagastrin slightly stimulated insulin, but not glucagon, secretion. The insulin secretory activity of pentagastrin was only 1/300 that of ccx-8 on a molar basis. The threshold dose of ccx-8 for stimulation of insulin secretion was similar to that for exocrine pancreatic secretion obtained in earlier studies. In conclusion, ccx is a potential candidate as a physiological factor regulating insulin secretion in sheep.     

Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies

OBJECTIVE: To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. ANIMALS: 10 ponies. PROCEDURE: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during anesthesia. Five ponies received atipamezole (60 microg/kg) during recovery. RESULTS: During anesthesia, mean cardiac index and heart rate increased significantly until 150 minutes, then decreased until cessation of anesthesia. Mean arterial pressure and systemic vascular resistance index increased significantly between 150 minutes and 4 hours. In 4 ponies, PaO2 decreased to < 60 mm Hg. Mean blood propofol concentrations from 20 minutes after induction onwards ranged from 2.3 to 3.5 microg/ml. Recoveries were without complications and were complete within 28 minutes with atipamezole administration and 39 minutes without atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: During total IV anesthesia of long duration with medetomidine-propofol, cardiovascular function is comparable to or better than under inhalation anesthesia. This technique may prove suitable in equids in which prompt recovery is essential; however, in some animals severe hypoxia may develop and oxygen supplementation may be necessary.     

Cardiac performance in conscious healthy dogs during dobutamine infusion

The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 275 to 50 pg kg⁻¹ min⁻¹ -1 induced a significant rise in cardiac power index ( ), cardiac index ( ), stroke index ( ) and heart rate ( ) and a significant decrease in pulmonary vascular resistance ( ) and systemic vascular resistance ( ). The highest CPI was 2·05 times greater than its basal resting value. The CI was primarily responsible for this increase in . The si and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in .     

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10 min of dobutamine infusion (2 µg kg⁻¹ min⁻¹). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.     

The anti-nociceptive and cardiopulmonary effects of extradural fentanyl–xylazine in sheep

Objective To compare the anti‐nociceptive effects of extradural xylazine, fentanyl and a xylazine–fentanyl combination in sheep, and to measure the cardiopulmonary effects of the xylazine–fentanyl combination. Study design Prospective, randomized study. Animals Twenty‐five half‐merino ewes 2–4 years of age and body mass 54.2 ± 1.1 kg. Methods Six sheep in group 1 received 0.2 mg kg^?1 xylazine by extradural injection, six in group 2 received fentanyl 1.5 µg kg^?1 and 13 in group 3 received the combination of both treatments. In all groups, drugs were mixed with saline (0.15 mL kg^?1 before injection). Pulmonary and carotid arterial catheters were placed in seven sheep of group 3 which were used to evaluate cardiopulmonary effects. Anti‐nociception was determined by the response to electrical stimulation (40 V for 1.5 milliseconds) of the left flank and by superficial and deep muscular ‘pinpricking’ stimulation of the pelvic and thoracic limbs and thoracolumbar region. Results Lack of response to electrical stimulation at the left flank was present in 10 ± 1.1 minutes (mean ± SEM) (group 1) and in 4.5 ± 0.5 minutes in group 3. The duration of lack of response to electrical stimulation at the left flank was 96 ± 6 minutes in group 1 and 315 ± 6 minutes in group 3. Responses persisted in group 3. Significant decreases (p < 0.05) in cardiac output 30, 45, 60 and 90 minutes after injection, and in cardiac work at 30 and 45 minutes were observed in the seven animals of group 3. Arterial blood pH was lowest at 90 minutes, arterial bicarbonate was lowest at 60 minutes and values for both arterial and mixed venous base excess increased significantly at 60 and 90 minutes. There was no significant change from baseline values in heart rate, mean arterial blood pressure, respiratory rate, body temperature, systemic vascular resistance, arterial and mixed venous PO₂, PCO₂, oxygen saturation, blood oxygen content, haemoglobin concentration, mixed venous blood bicarbonate and pH. Conclusions Fentanyl decreases the onset time and prolongs the duration of anti‐nociception produced by xylazine. The combination decreases cardiac output but is without significant respiratory effects. Clinical relevance Further studies are required to show that surgery is possible in sheep after extradural xylazine–fentanyl injection.     

Observations on some cardiopulmonary effects of midazolam, xylazine and a midazolam/ketamine combination in the goat

Xylazine, midazolam and a midazolam/ketamine combination were administered to 6 goats in a randomised 3-way block design. All goats received all treatments with at least a 7-day interval between treatments. Statistically significant (P < 0.05) changes were observed in some of the measured cardiopulmonary variables for xylazine and midazolam/ ketamine. Xylazine administration resulted in statistically significant decreases in minute volume, arterial partial pressure of oxygen, heart rate and mean arterial blood pressure. The increase in arterial partial pressure of carbon dioxide was not statistically significant. For the midazolam/ketamine combination, the decrease in tidal volume was statistically significant, but not the decrease in minute volume and increase in arterial partial pressure of carbon dioxide. The decrease in the arterial partial pressure of oxygen was also statistically significant. The mean arterial blood pressure for the combination was statistically significantly higher compared to xylazine. The changes in cardiopulmonary variables after midazolam administration were not statistically significant, such as tidal and minute volume, arterial partial pressure of oxygen and carbon dioxide. However, clinically significant effects such as hypoventilation and hypoxia were observed after its administration. The change in mean arterial blood pressure was minimal.     

The influence of body mass and thoracic dimensions on arterial oxygenation in anaesthetized horses and ponies

ObjectiveTo examine the relationship between body mass and thoracic dimensions on arterial oxygen tensions (PaO₂) in anaesthetized horses and ponies positioned in dorsal recumbency.Study designProspective clinical study.AnimalsThirty six client-owned horses and ponies, mean [±SD (range)] age 8.1 ± 4.8 (1.5–20) years and mean body mass 467 ± 115 (203–656) kg.MethodsBefore general anaesthesia, food and water were withheld for 12 and 1 hours respectively. Body mass (kg), height at the withers (H), thoracic circumference (C), thoracic depth (length between dorsal spinous process and sternum; D), thoracic width (between point of shoulders; W), and thoracic diagonal length (point of shoulder to last rib; L) were measured. Pre-anaesthetic medication was with intravenous (IV) romifidine (0.1 mg kg⁻¹). Anaesthesia was induced with an IV ketamine (2.2 mg kg⁻¹) and diazepam (0.05 mg kg⁻¹) combination and maintained with halothane in 1:1 oxygen:nitrous oxide (N₂O) mixture. Animals were positioned in dorsal recumbency and allowed to breathe spontaneously. Nitrous oxide was discontinued after 10 minutes, and arterial blood samples obtained and analysed for gas tensions at 15, 30 and 60 minutes after connection to the anaesthetic breathing circuit. Data were analysed using anova and Pearson's correlation co-efficient.ResultsThe height per unit body mass (H kg⁻¹) and thoracic circumference per unit body mass (C kg⁻¹) correlated strongly (r = 0.85, p < 0.001 and r = 0.82, p < 0.001 respectively) with arterial oxygen tensions (PaO₂) at 15 minutes.ConclusionsThere is a strong positive correlation between H kg⁻¹ and C kg⁻¹ and PaO₂ after 15 minutes of anaesthesia in halothane-anaesthetized horses positioned in dorsal recumbency.Clinical relevanceReadily obtained linear measurements (height and thoracic circumference) and body mass may be used to predict the ability of horses to oxygenate during anaesthesia.     

Influence of route of administration on the plasma concentrations of ivermectin in reindeer

The concentration of ivermectin in the plasma of reindeer was measured after it was administered either topically as a pour-on preparation at 500 μg kg⁻¹ bodyweight at different seasons to animals of different ages, or after subcutaneous and oral doses of 200 μg kg⁻¹ bodyweight. The plasma concentrations of ivermectin were highest and least variable after it was administered subcutaneously.     

Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

ObjectiveTo evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.Study designProspective single-group interventional study.AnimalsA group of six healthy adult research ponies (four mares, two geldings).MethodsPonies were sedated with intravenous (IV) detomidine (0.02 mg kg^–1) and butorphanol (0.01 mg kg^–1) for an unrelated study. Additional IV detomidine (0.004 mg kg^–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg^–1) and ketamine (2.2 mg kg^–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg^–1) with fenpipramide (0.0125 mg kg^–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05).ResultsPlasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg^–1 and plasma clearance 7.77 ± 1.98 mL minute^–1 kg^–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.Conclusions and clinical relevanceAdministration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine–hydromorphone, and medetomidine–butorphanol in dogs

The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg^?1), medetomidine–hydromorphone (MH, 20 µg kg^?1 ? 0.1 mg kg^?1), and medetomidine–butorphanol (MB, 20 µg kg^?1 ? 0.2 mg kg^?1) in dogs. Using a randomized cross‐over design and allowing 1 week between treatments, six healthy, mixed‐breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face‐mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post‐injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe‐pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post‐injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No differences in CV variables between treatment groups were identified at any time. PaO₂ increased over time in all groups and was significantly higher when MH was compared with M. At 45 minutes, PaO₂ tended to decrease over time and was significantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were significantly higher compared with M through 45 minutes, while analgesia scores for MH were significantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108 ± 10.8, 172 ± 15.5, and 145 ± 9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CV effects when compared with M.     

The utility of a novel formulation of alfaxalone in a remote delivery system

ObjectiveTo quantify induction time, reliability, physiological effects, recovery quality and dart volume of a novel formulation of alfaxalone (40 mg mL^?1) used in combination with medetomidine and azaperone for the capture and handling of wild bighorn sheep.Study designProspective clinical study.AnimalsA total of 23 wild bighorn sheep (Ovis canadensis) in Sheep River Provincial Park, AB, Canada.MethodsFree-ranging bighorn sheep were immobilized using medetomidine, azaperone and alfaxalone delivered with a remote delivery system. Arterial blood was collected for measurement of blood gases, physiologic variables (temperature, heart and respiratory rates) were recorded and induction and recovery length and quality were scored.ResultsData from 20 animals were included. Administered dose rates were alfaxalone (0.99 ± 0.20 mg kg^?1; 40 mg mL^?1), azaperone (0.2 ± 0.04 mg kg^?1; 10 mg mL^?1) and medetomidine (0.16 ± 0.03 mg kg^?1; 30 mg mL^?1). The mean drug volume injected was 1.51 mL. The median (range) induction time was 7.7 (5.8–9.7) minutes, and recovery was qualitatively smooth.Conclusions and clinical relevanceAn increased concentration formulation of alfaxalone was administered in combination with medetomidine and azaperone, and resulted in appropriate anesthesia for the capture and handling of bighorn sheep. The dart volume was small, with potential for reducing capture-related morbidity.