Clinical comparison of preanaesthetic intramuscular medetomidine and dexmedetomidine in domestic sheep.

Medetomidine and its active d-enantiomer, dexmedetomidine, are highly selective alpha-2 agonists with potent sedative, anaesthetic-sparing and analgesic effects. These properties make them an ideal pre-anaesthetic medication for noxious surgical procedures. However, sheep can develop adverse hypoxaemic effects after intravenous alpha-2 agonists. Objective of the present study was to compare intramuscular injection of medetomidine or dexmedetomidine at equipotent doses as preanaesthetic medication prior to isoflurane anaesthesia in sheep. Nineteen healthy, adult, non-pregnant, female sheep of various breeds were used. The study was carried out as a randomised, blind trial. Group A received 15 micrograms/kg bwt dexmedetomidine and group B received 30 micrograms/kg bwt medetomidine intramuscularly (i.m.) 30 minutes prior to induction of anaesthesia. Anaesthesia was induced with ketamine (2.0 mg/kg bwt i.v.) and maintained with isoflurane in 100% oxygen. End expired anaesthetic concentration (FEiso), respiratory frequency (fR), direct arterial blood pressures and heart rates (HR) were measured. Arterial blood samples were taken at intervals. Data were averaged over time (sum of measurements/number of measurements) and tested for differences between groups by independent t-tests, and ANOVA for repeated measures followed by Bonferroni corrected t-tests. There were no differences in demographic data between the groups. Duration of anaesthesia [A: 170 (42) minutes, B: 144 (33) minutes] and duration of surgery [A: 92 (32) minutes, B: 85 (31) minutes] were similar in both groups. Average FEiso concentrations required to maintain a surgical plane of anaesthesia were not significantly different between groups [A: 0.82 (0.14)%; B: 1.00 (0.25)%]. Mean average fR, did not differ between groups [A: 31 (14), B: 37 (15)]. Heart rates were significantly lower in group B over the course of the anaesthesia. Mean arterial blood pressures (MAP) were not significantly different between the groups. The PaO2 was less variable in group A than in group B. Individual minimum values were 19.1 kPa and 7.9 kPa in group A and B, respectively. There were no significant differences in PaCO2 and paH between the groups and over time. In conclusion, intramuscular application of dexmedetomidine at 15 micrograms/kg bwt and medetomidine at 30 micrograms/kg bwt prior to isoflurane anaesthesia induced similar changes in clinically monitored cardiorespiratory parameters. The observed differences (heart rates, PaO2) between dexmedetomidine and medetomidine at the chosen dose relationship can be considered clinically not significant. At the chosen dose rates individual animals responded with a transient drop in blood oxygenation, therefore careful monitoring is required. In addition, in compromised sheep medetomidine and dexmedetomidine should be used carefully.     

Pharmacokinetics and sedative effects of intramuscular medetomidine in domestic sheep

Intramuscular (i.m.) administration of medetomidine (MED) may avoid the severe pressor effects caused by peripheral actions of MED associated with intravenous (i.v.) dosing. The purpose of this study was to determine the pharmacokinetics, the time course of sedation and occurence of hypoxaemia after i.m. administration of MED in domestic sheep. The MED was injected i.m. at a dose of 30 micro g/kg in nine domestic sheep. Blood was sampled at 0, 5, 10, 20, 30, 40, 60, 120, 180, 240, 360 and 600 min after MED. Sedation was assessed and arterial blood samples were taken before and 35 min after MED application. Mean (SD) pharmacokinetic parameters of i.m. MED were: absorption half-life: 13.2 (7.5) min; terminal half-life: 32.7 (14.9) min; time to peak concentration: 29.2 (8.9) min; peak concentration: 4.98 (1.89) ng/mL; volume of distribution: 3.9 (2.4) l/kg; total body clearance: 81.0 (21.5) mL/(min kg). Peak sedation occurred between 30 and 40 min after injection of MED. The degree of sedation correlated with individual plasma concentrations (rS: 0.926). One animal became hypoxaemic (PaO2 = 54.1 mmHg).     

Investigating medetomidine-buprenorphine as preanaesthetic medication in cats

O bjectives : The objective of this study was to investigate medetomidine-buprenorphine preanaesthetic medication in cats.
M ethods : Forty American Society of Anesthesiologists (ASA) I female cats were enrolled in this prospective, blinded, clinical study. Cats were randomised into one of four groups: group M30 were injected intramuscularly with 30 μg/kg medetomidine, groups M10+B, M30+B and M50+B received 10, 30 and 50 μg/kg of medetomidine, respectively, each in combination with 20 μg/kg buprenorphine. After 30 minutes, a sedation score was allocated. Anaesthesia was induced using intravenous propofol and maintained using isoflurane in oxygen, while cats underwent ovariohysterectomy. Heart rate, respiratory rate, end-tidal carbon dioxide tension and oxygen saturation of haemoglobin were recorded. Atipamezole was administered intramuscularly at volatile agent discontinuation. Time taken to lift their head, sit in sternal and stand were recorded along with quality of recovery.
R esults : M30+B cats required significantly less isoflurane compared with M30 cats. Heart rate and oxygen saturation of haemoglobin were significantly lower in M50+B cats than in M30 cats. All M+B groups experienced significantly better recoveries compared with the medetomidine only M30 control group.
C linical S ignificance : The addition of buprenorphine to medetomidine preanaesthetic medication in cats reduces volatile agent vaporiser setting and improves the quality of recovery from anaesthesia.     

Comparison of epidural versus intrathecal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery

ObjectiveTo compare the procedural failure rate (PFR), intraoperative rescue analgesia (iRA) probability and postoperative duration of motor block after epidural and intrathecal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery.Study designProspective, randomized clinical trial.AnimalsNinety-two client-owned dogs.MethodsDogs were assigned randomly to receive either lumbosacral epidural anaesthesia (EA) (bupivacaine 0.5% and morphine 1%) or intrathecal anaesthesia with the same drugs in a hyperbaric solution (HIA). Inaccurate positioning of the needle, assessed by radiographic imaging, and lack of cerebral spinal fluid outflow were considered procedural failures (PFs) of EA and HIA, respectively. Fentanyl (1 μg kg⁻¹ IV) was provided for intraoperative rescue analgesia, when either the heart rate or the mean arterial pressure increased by 30% above the pre-stimulation value. Its use was recorded as a sign of intraoperative analgesic failure. The motor block resolution was evaluated postoperatively. Variables were compared using Fisher's exact test, the Mann–Whitney U test and the Kaplan–Meier ‘survival’ analysis as relevant.ResultsThe PFRs in the EA and HIA groups were 15/47 (32%) and 3/45 (7%), respectively (p = 0.003). Differences in iRA were analysed in 26 and 30 subjects in the EA and HIA groups respectively, using Kaplan–Meier survival analysis. The iRA probability within the first 80 minutes of needle injection (NI) was higher in the EA group (p = 0.045). The incidence of dogs walking within 3 hours of NI was significantly higher in the HIA group (8/20, 40%) than in the EA group (0/17) (p = 0.004).Conclusions and clinical relevanceHIA was found to have lower PF, lower intraoperative analgesic failure and faster motor block resolution. In this study HIA was shown to provide some advantages over EA in dogs undergoing commonly performed pelvic limb orthopaedic surgery in a day-hospital regime.     

Comparison of two pre-anaesthetic medetomidine doses in isoflurane anaesthetized sheep

OBJECTIVE: To compare the sedative, anaesthetic-sparing and arterial blood-gas effects of two medetomidine (MED) doses used as pre-anaesthetic medication in sheep undergoing experimental orthopaedic surgery. STUDY DESIGN: Randomized, prospective, controlled experimental trial. ANIMALS: Twenty-four adult, non-pregnant, female sheep of various breeds, weighing 53.9 +/- 7.3 kg (mean +/- SD). METHODS: All animals underwent experimental tibial osteotomy. Group 0 (n = 8) received 0.9% NaCl, group L (low dose) (n = 8) received 5 microg kg(-1) MED and group H (high dose) (n = 8) received 10 microg kg(-1) MED by intramuscular (IM) injection 30 minutes before induction of anaesthesia with intravenous (IV) propofol 1% and maintenance with isoflurane delivered in oxygen. The propofol doses required for induction and endtidal isoflurane concentrations (F(E')ISO) required to maintain anaesthesia were recorded. Heart and respiratory rates and rectal temperature were determined before and 30 minutes after administration of the test substance. The degree of sedation before induction of anaesthesia was assessed using a numerical rating scale. Arterial blood pressure, heart rate, respiratory rate, FE'ISO, end-tidal CO2 (FE'CO2) and inspired O2 (FIO2) concentration were recorded every 10 minutes during anaesthesia. Arterial blood gas values were determined 10 minutes after induction of anaesthesia and every 30 minutes thereafter. Changes over time and differences between groups were examined by analysis of variance (anova) for repeated measures followed by Bonferroni-adjusted t-tests for effects over time. RESULTS: Both MED doses produced mild sedation. The dose of propofol for induction of anaesthesia decreased in a dose-dependent manner: mean (+/-SE) values for group 0 were 4.7 (+/-0.4) mg kg(-1), for group L, 3.2 (+/-0.4) mg kg(-1) and for group H, 2.3 (+/-0.3) mg kg(-1)). The mean (+/-SE) FE'ISO required to maintain anaesthesia was 30% lower in both MED groups [group L: 0.96 (+/-0.07) %; group H: 1.06 (+/-0.09) %] compared with control group values [(1.54 +/- 0.17) %]. Heart rates were constantly higher in the control group with a tendency towards lower arterial blood pressures when compared with the MED groups. Respiratory rates and PaCO2 were similar in all groups while PaO2 increased during anaesthesia with no significant difference between groups. In group H, one animal developed a transient hypoxaemia: PaO2 was 7.4 kPa (55.7 mmHg) 40 minutes after induction of anaesthesia. Arterial pH values and bicarbonate concentrations were higher in the MED groups at all time points. CONCLUSION AND CLINICAL RELEVANCE: Intramuscular MED doses of 5 and 10 microg kg(-1) reduced the propofol and isoflurane requirements for induction and maintenance of anaesthesia respectively. Cardiovascular variables and blood gas measurements remained stable over the course of anaesthesia but hypoxaemia developed in one of 16 sheep receiving MED.     

Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration

Cats ( n  = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 μg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 μg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5±16.0 min) than after MED (230.0±41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5±38.4 min) than after MED (by 14.2±41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1±13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 μg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.     

Comparing oral and intramuscular administration of medetomidine in cats

Medetomidine (200 μg/kg) was administered orally and, on a seperate occasion, im to 7 cats. Peak serum drug concentrations were reached more slowly after oral (43.6 ± 14.3 min) than after im administration (21.6 ± 10.0 min). The onset of sedation and recumbency lagged after oral administration. There were no statistically significant differences between the 2 routes of administration in peak serum concentrations, systemic drug availability or extent of sedation. However, there was considerable variation in these parameters between individuals after oral administration. The extent of salivation correlated negatively with systemic drug availability after oral administration. Where excessive salivation did not occur, systemic drug availability and the depth of sedation were comparable to, or even higher than, were obtained after the corresponding im administrations. In conclusion, oral administration of medetomidine induced a clinical sedation but, when accurate dosing is a necessity, the oral route may not be very reliable due to possible drug losses through salivation.     

Comparison of the analgesic effects of meloxicam and carprofen administered preoperatively to dogs undergoing orthopaedic surgery

Thirty-two dogs undergoing operations to repair a torn cranial cruciate ligament or a fractured long bone were randomly allocated to one of two treatment groups in a study on postoperative pain. Sixteen of the dogs were given 4 mg/kg carprofen and the other 16 were given 0.2 mg/kg meloxicam subcutaneously before the operation. The signs of pain shown by the animals were assessed for 24 hours on a visual analogue scale, a discontinuous scoring system, and a score based on five behavioural and physiological variables. The dogs' heart and respiratory rates and their mean arterial blood pressures were also measured non-invasively at each assessment. Blood samples were taken before the surgery and 24 hours after it, and the concentrations of urea and creatinine were measured in plasma. Both drugs were effective in relieving the signs of pain for up to 24 hours in all the dogs. There were no significant changes in the concentrations of urea and creatinine, and no adverse effects were reported during the postoperative period.     

Metabolic and clinical traits in horses undergoing feed deprivation for elective orthopaedic surgery

The objective of this study was to investigate some metabolic and clinical effects of feed deprivation in horses that were submitted for orthopaedic surgery. The effects of preoperative feed restriction were investigated in 20 horses submitted for elective orthopaedic surgery.The patients were fasted from 12 hours before until 4 hours after surgery. Serum free amino acids, glucose,free fatty acids (FFA), white blood cell counts, creatine kinase (CK) and aspartate aminotransferase (AST) were determined 24 hours before surgery, 2 hours after the end of anaesthesia and 24 and 72 hours after surgery. Besides, abdominal sounds, appetite, faecal quality and body temperature were examined. Serum free amino acids did not react homogenously, concentrations were partly increasing or decreasing. Plasma glucose and FFA increased after surgery and returned to their preoperative levels 72 hours after surgery. A significant rise of the segmented granulocytes occurred 24 hours after surgery, all other parameters of the leukogram did not exceed the physiological range. AST reached its highest activity 24 hours after surgery, whereas CK activities were highest at 2 hours after surgery. Abdominal sounds were significantly reduced until 24 hours after surgery, however, appetite was not depressed. Faecal quality was physiological after surgery. Mean body temperature stayed within the physiological range. In conclusion, a relatively short perioperative fasting period had significant effects on the metabolic traits in horses, however the effects on physiological functions were minor. The consequences of major surgical procedures need to be addressed in future studies.     

Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia.

OBJECTIVE: To compare 3 dose levels of medetomidine and dexmedetomidine for use as premedicants in dogs undergoing propofol-isoflurane anesthesia. ANIMALS: 6 healthy Beagles. PROCEDURE: Dogs received medetomidine or dexmedetomidine intravenously at the following dose levels: 0.4 microg of medetomidine or 0.2 microg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 microg of medetomidine or 2.0 microg of dexmedetomidine/kg (M4/D2), and 40 microg of medetomidine or 20 microg of dexmedetomidine/kg (M40/D20). Sedation and analgesia were scored before induction. Anesthesia was induced with propofol and maintained with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial blood pressures and gases were measured. RESULTS: Degrees of sedation and analgesia were significantly affected by dose level but not drug. Combined mean end-tidal isoflurane concentration for all dose levels was higher in dogs that received medetomidine, compared with dexmedetomidine. Recovery time was significantly prolonged in dogs treated at the M40/D20 dose level, compared with the other dose levels. After induction, blood pressure decreased below reference range and heart rate increased in dogs treated at the M0.4/D0.2 dose level, whereas blood pressure was preserved in dogs treated at the M40/D20 dose level. However, dogs in these latter groups developed profound bradycardia and mild metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted in more stable cardiovascular effects, compared with the other dose levels. In addition, PaCO2 was similar among dose levels. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia.     

Single dose pharmacokinetics of medetomidine in sheep

The pharmacokinetics of medetomidine hydrochloride (Domitor) administered at a single dose of 15 μg/kg IV in sheep are described. Plasma medetomidine concentrations were determined using a sensitive radioreceptor assay technique, capable of also measuring metabolites which would bind to α₂ adrenergic receptors. Medetomidine was rapidly distributed, with a half-life of distribution of 4.65/pm0.65 min. The apparent volume of distribution was 2.69/pm0.62 L/kg, while elimination half-life was 37.85/pm2.84 min. Total body clearance varied between 16.29 and 151.81 mL/min.kg. Pharmacological effects of medetomidine paralleled its plasma concentration.     

Effect of gonadectomy on pain assessment in dogs undergoing orthopaedic stifle surgery

ObjectiveTo compare pain perception between gonadectomized and intact dogs.Study designBlinded, prospective, cohort study.AnimalsA group of 74 client-owned dogs.MethodsDogs were divided into four groups: group 1—female/neutered (F/N), group 2—female/intact (F/I), group 3—male/neutered (M/N) and group 4—male/intact (M/I). Premedication consisted of intramuscularly administered acepromazine (0.05 mg kg⁻¹) and morphine (0.2 mg kg⁻¹), and subcutaneously administered carprofen (4 mg kg⁻¹). Anaesthesia was induced with propofol (1 mg kg⁻¹ intravenously and supplementary doses to effect) and maintained with isoflurane in 100% oxygen. Intraoperative analgesia was achieved with fentanyl infusion (0.1 μg kg⁻¹ minute⁻¹). Pain assessments [using the University of Melbourne Pain Scale (UMPS) and an algometer at the incision site (IS), parallel to the incision site (NIS), and on the contralateral healthy limb] were performed preoperatively, and at 1, 2, 4, 6, 9 and 20 hours after extubation. The time-standardised area under the curve (AUCst) for measurements was calculated and compared by performing a one-way multivariate analysis of variance (manova). Statistical significance was set at p < 0.05.ResultsPostoperatively, F/N exhibited higher pain than F/I, with estimated marginal means (95% confidence intervals) AUCstIS_Group1 909 (672–1146) versus AUCstIS_Group2 1385 (1094–1675) (p = 0.014), AUCstNIS_Group1 1122 (823–1420) versus AUCstNIS_Group2 1668 (1302–2033) (p = 0.024) and AUCstUMPS_Group1 5.30 (4.58–6.02) versus AUCstUMPS_Group2 4.1 (3.2–5.0) (p = 0.041). Similarly, M/N showed higher pain than M/I with AUCstIS_Group3 686 (384–987) versus AUCstIS_Group4 1107 (871–1345) (p = 0.031) and AUCstNIS_Group3 856 (476–1235) versus AUCstNIS_Group4 1407 (1109–1706) (p = 0.026), and AUCstUMPS_Group3 6.0 (5.1–6.9) versus AUCstUMPS_Group4 4.4 (3.7–5.2) (p = 0.008).Conclusions and clinical relevance:Gonadectomy affects pain sensitivity in dogs undergoing stifle surgery. Neutering status should be taken into consideration when planning individualized anaesthetic/analgesic protocols.     

The use of intraoperative fentanyl in spontaneously breathing dogs undergoing orthopaedic surgery

Nineteen dogs were assigned randomly to one of three groups. Animals in Group 1 were pre-medicated with acepromazine, 50 μg/kg bodyweight (bwt) intramuscularly (im) and received 10 ml of 0.9 per cent saline intravenously (iv) at the time of skin incision. Dogs in Group 2 were pre-medicated with acepromazine, 50 μg/kg bwt im, and received fentanyl 2 μg/kg bwt iv at skin incision. Dogs in Group 3 were pre-medicated with acepromazine, 50 μg/kg bwt and atropine, 30 to 40 μg/kg bwt, im and received fentanyl, 2 μg/kg bwt iv at skin incision. Pulse rate, mean arterial blood pressure, respiratory rate and end tidal carbon dioxide were measured before and after fentanyl or saline injection. Fentanyl caused a short-lived fall in arterial blood pressure that was significant in dogs premedicated with acepromazine, but not in dogs pre-medicated with acepromazine and atropine. A significant bradycardia was evident for 5 mins in both fentanyl treated groups. The effect on respiratory rate was most pronounced in Group 3, in which four of seven dogs required intermittent positive pressure ventilation (IPPV) for up to 14 mins. Two of six dogs in Group 2 required IPPV, whereas respiratory rate remained unaltered in the saline controls. The quality of anaesthesia was excellent in the fentanyl treated groups; however, caution is urged with the use of even low doses of fentanyl in spontaneously breathing dogs under halothane-nitrous oxide anaesthesia.     

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.     

Cardiopulmonary effects of medetomidine in sheep and in ponies

Medetomidine was administered intravenously to six sheep at 5, 10 and 20 μg kg⁻¹ and to one horse and four ponies at 5 and 10 μg kg⁻¹. In both species medetomidine resulted in significant decreases in heart rate and cardiac output and, initially, in an increase in arterial blood pressure. In the ponies this increase in blood pressure was followed by a significant and prolonged decrease, but in the sheep the secondary decrease in blood pressure was not statistically significant. In the sheep, the three doses of medetomidine resulted in profound and significant decreases in arterial oxygen tensions, which were significantly dose related, but in the ponies the arterial blood oxygen tensions were not significantly decreased. In both species medetomidine caused a small but significant increase in arterial blood carbon dioxide tensions.     

Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic surgery

The buccal mucosal bleeding time (BMBT), prothrombin time (PT), activated partial thromboplastin time (APTT) and intraoperative bleeding score (IBS) of 38 dogs that underwent orthopaedic surgical procedures and received meloxicam orally and/or parenterally were measured. Fourteen of the dogs (group A) received a single subcutaneous dose of 0.2 mg/kg meloxicam at premedication, 18 dogs (group B) received 0.1 mg/kg meloxicam orally daily for five days followed by a single subcutaneous dose of 0.2 mg/kg meloxicam preoperatively, and six dogs (group C) received 0.5 ml of normal saline subcutaneously at premedication. No statistically significant differences among the groups were detected in relation to the mean (SD) values of BMBT, PT and IBS before and after the surgery, or in the values of APTT in group A. In group B there was a small but significant increase in APTT after the surgery, but all the measurements were within the normal range for dogs.