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).     

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.     

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.     

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.     

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 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.     

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.     

Effects of preoperative epidural administration of racemic ketamine for analgesia in sheep undergoing surgery

OBJECTIVE: To investigate the effects of preoperative epidural administration of racemic ketamine to provide analgesia in sheep undergoing experimental hind limb orthopedic surgery. ANIMALS: 12 adult sheep (weight range, 51.4 to 67.2 kg). PROCEDURE: Sheep were anesthetized with guaifenesin, thiopental, and isoflurane; after induction of anesthesia, sheep received a lumbosacral epidural injection of ketamine (1 mg/kg; n = 6) or saline (0.9% NaCl) solution (1 mL/7 kg; 6 [control group]). Respiratory and cardiovascular variables were recorded before and at intervals during and for 6 hours after anesthesia. During that 6-hour postoperative period, analgesia was evaluated subjectively with a numeric ranking scale that included assessments of comfort, posture, movement, and response to wound palpation; buprenorphine was administered when a score > 3 (maximum score, 10) was achieved. Rectal temperature, heart and respiratory rates, and lameness were evaluated daily for 2 weeks after surgery. RESULTS: At all evaluations, cardiovascular and respiratory variables were comparable between the 2 groups. Compared with control sheep, time to first administration of rescue analgesic was significantly longer and total dose of buprenorphine administered during the 6- hour postoperative period was significantly decreased for ketamine-treated sheep. During the second week following surgery, ketamine-treated sheep had significantly less lameness than control sheep. CONCLUSIONS AND CLINICAL RELEVANCE: In sheep undergoing hind limb surgery, preoperative epidural administration of ketamine appears to provide analgesia in the immediate postoperative period and has residual analgesic effects, which may contribute to more rapid return of normal function in surgically treated limbs.     

Complications in orthopaedic surgery

Complications in orthopaedic surgery.     

Effects of combinations of medetomidine/pethidine when used for sedation and pre-anaesthetic medication in dogs

Medetomidine, either 5, 10 or 20 (μg/kg, was administered together with pethidine, 2 mg/kg, by either the intramuscular or subcutaneous route to 88 dogs from a clinical population. Administration of all the drug combinations consistently produced profound sedation in the dogs, accompanied by dramatic reductions in heart rate. The degree of sedation was similar to that seen after 40 μg/kg medetomidine is administered on its own to dogs. Intramuscular administration produced more reliable sedation, but was associated with more pain than subcutaneous administration. In a number of dogs, sedation permitted the completion of various diagnostic or therapeutic procedures. Several dogs were anaesthetised with thiopentone and the induction doses required were characteristically low (mean doses between 2 to 3·3 mg/kg depending on the dose of medetomidine and the route of administration). Administration of atipamezole at the termination of sedation or anaesthesia, produced a rapid and full recovery (mean time to standing between seven and 11 minutes).     

Noxious stimulation during orthopaedic surgery results in EEG 'arousal' or 'paradoxical arousal' reaction in isoflurane-anaesthetised sheep

The effects of surgical stimuli on haemodynamic and electroencephalographic (EEG) variables were determined in 25 adult ewes undergoing an experimental orthopaedic procedure in isoflurane anaesthesia. Data were recorded after 15 min of constant end-tidal concentration of approximately 2.2% isoflurane (SS: steady state=baseline), during skin disinfection (DIS), incision (INC), drilling of the first hole through the tibia (DRI) and insertion of a threaded pin (PIN) for external fixation. Stimulation resulted in a significant increase in systolic and mean arterial pressure above SS at INC, DRI and PIN. Haemodynamic changes were accompanied by either significant increases or decreases in EEG median frequency (MF) and 80% spectral edge frequency (SEF80) above or below SS at all four stimulation time points suggesting 'arousal' or 'paradoxical arousal' reaction, respectively. We conclude, that either type of EEG activation pattern could be elicited dependent on stimulation intensity and level of anaesthetic depth.     

Clinical use of a low-dose medetomidine infusion in healthy dogs undergoing ovariohysterectomy

Eight healthy dogs undergoing elective ovariohysterectomy were anesthetized with a standard protocol and received a low-dose medetomidine constant rate infusion during surgery. Cardiorespiratory parameters, including non-invasive cardiac output, were measured at various times. This protocol resulted in acceptable and stable cardiovascular performance, allowed low isoflurane concentrations, and provided smooth recoveries.