Anaesthetic and cardiorespiratory effects of ketamine plus dexmedetomidine for chemical restraint in black capuchin monkeys (Sapajus nigritus)

AIMS: To evaluate the quality of anaesthesia and cardiorespiratory effects of ketamine and two doses of dexmedetomidine in captive black capuchin monkeys (Sapajus nigritus) undergoing routine clinical examination.

METHODS: Twenty-four animals undergoing routine clinical examination were enrolled in the study. Animals were briefly physically restrained and examined to ensure no obvious illness was present and that they were healthy. Monkeys were randomly allocated to two groups (n=12 per group) and then treated with a combination of I/M 7.5?mg/kg ketamine and either 30?µg/kg or 50?µg/kg dexmedetomidine (Dex30 or Dex50 groups, respectively). Interval to onset and duration of anaesthesia were recorded, and the quality of induction of anaesthesia and recovery were subjectively evaluated. Heart rate, respiratory rate, systolic arterial pressure (SAP), rectal temperature, degree of sedation, analgesia, muscle relaxation and response to auditory stimulus were measured every 5 minutes from onset of anaesthesia until recovery.

RESULTS: The mean interval to onset of anaesthesia was 7.3 (SD 6.6) and 9.1 (SD 5.0) minutes for the Dex30 and Dex50 groups, respectively (p=0.208). Mean duration of anaesthesia was longer for monkeys in the Dex50 (85.5 (SD 15.3) minutes) compared to those in Dex30 (63.9 (SD 16.4) minutes) group (p=0.003). Induction was considered excellent in 23/24 animals, and recovery was excellent in all animals. Heart rate, respiratory rate and body temperature decreased in both groups when compared to baseline, with no differences between groups. No differences between groups were found for assessments of sedation, analgesia, muscle relaxation or response to auditory stimulus.

CONCLUSION AND CLINICAL RELEVANCE: Administration of ketamine and dexmedetomidine at the two doses produced adequate, dose-dependent chemical restraint, with excellent induction and recovery, and minimal clinically significant cardiorespiratory effects in captive capuchin monkeys. Due to the occurrence of arrhythmias, electrocardiographic monitoring is recommended when this combination is used. The administration of higher doses of dexmedetomidine produced longer lasting anaesthesia without further compromise of cardiorespiratory parameters.     

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.     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.     

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12?sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 μg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and?alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150-166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P?=?0). Also, heart rate (P?=?0), cardiac index (P?=?0.002), stroke index (P?=?0) and contractility (P?=?0) were higher, and systemic vascular resistance (P?=?0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO(2) between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.     

Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia

This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed-ranked test with p < .05 considered significant. Elimination half-lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady-state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.     

Evaluation of the sedative and clinical effects of xylazine,detomidine, medetomidine and dexmedetomidine in miniature donkeys

ABSTRACT

Aim: To evaluate the sedative and clinical effects of I/V xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.

Methods: Seven clinically healthy, male adult miniature donkeys with a mean age of 6 years and weight of 105?kg, were assigned to five I/V treatments in a randomised, cross-over design. They received either 1.1?mg/kg xylazine, 20?μg/kg detomidine, 10?μg/kg medetomidine, 5?μg/kg dexmedetomidine or saline, with a washout period of ≥7 days. The degree of sedation was scored using a 4-point scale by three observers, and heart rate (HR), respiration rate (RR), rectal temperature and capillary refill time (CRT) were recorded immediately before and 5, 10, 15, 30, 60, 90 and 120 minutes after drug administration.

Results: All saline-treated donkeys showed no sedation at any time, whereas the donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine had mild or moderate sedation between 5 and 60 minutes after treatment, and no sedation after 90 minutes. All animals recovered from sedation without complication within 2 hours. The mean HR and RR of saline-treated donkeys did not change between 0 and 120 minutes after administration, but the mean HR and RR of donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine declined between 5 and 60 minutes after drug administration. The mean rectal temperature of all treated donkeys did not change between 0 and 120 minutes after administration. The CRT for all donkeys was ≤2 seconds at all times following each treatment.

Conclusions and clinical relevance: Administration of xylazine at 1.1?mg/kg, detomidine at 20?μg/kg, medetomidine at 10?μg/kg and dexmedetomidine at 5?μg/kg resulted in similar sedation in miniature donkeys. Therefore any of the studied drugs could be used for sedation in healthy miniature donkeys.     

Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients

OBJECTIVE: To determine the effects of three rates of dexmedetomidine (DMED) constant rate infusion (CRI) on overall tissue perfusion, isoflurane (ISO) requirements, haemodynamics and quality of recovery in canine surgical patients. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Client-owned dogs presented for soft tissue or orthopaedic surgery. METHODS: Following intravenous (IV) pre-medication with DMED (5 microg kg(-1)) and buprenorphine (10 microg kg(-1)) and propofol induction, anaesthesia was maintained with ISO in oxygen/air supplemented with a DMED CRI (1, 2 or 3 microg kg(-1) hour(-1); groups 1, 2 and 3, respectively). Ventilation was controlled in all animals using intermittent positive pressure ventilation (IPPV). Monitoring included end-tidal (ET) gases, ECG, arterial blood pressure, body temperature and sequential arterial blood gas and lactate measurements. Quality of recovery was scored after intramuscular (IM) administration of atipamezole (ATI) (12.5 microg kg(-1)). Immediate post-operative analgesia was provided with carprofen and/or buprenorphine. An analysis of variance was conducted for repeated measurements obtained during 80 minutes after first incision. Categorical data were evaluated with Chi-square analyses. RESULTS: Arterial blood pressure remained stable and within clinically acceptable limits. Mean heart rate in group 2 was significantly lower than in group 1. The incidence of 2nd degree AV block type II was significantly higher in group 3. Mean arterial lactate concentrations remained below 2 mmol/L in all groups during the study, with a significant increase occurring during recovery compared with surgery for group 3. Mean e'ISO% was similar and <1% in all groups. Complete recovery from anaesthesia was achieved after ATI administration and was of good quality in all but three animals. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine CRI is a reliable and valuable adjunct to ISO anaesthesia in maintaining surgical anaesthesia in ASA I-II dogs. Data reported indicate adequate overall tissue perfusion and a low ISO requirement while enabling a smooth and rapid recovery following ATI. The DMED CRI of 1 microg kg(-1) hour(-1) following a loading dose of 5 microg kg(-1) produced the most favourable results.     

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1‐month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24‐h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography–tandem mass spectrometry. Plasma concentration–time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration–time curve (AUC) and the maximum plasma concentrations (C_max) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach C_max was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.     

Clinical use of dexmedetomidine as premedicant in cats undergoing propofol-sevoflurane anaesthesia

The purpose of this report was to evaluate the cardiorespiratory effects and efficacy of dexmedetomidine as a premedicant agent in cats undergoing ovariohysterectomy anaesthetized with propofol-sevoflurane. Cats were randomly divided into two groups of eight animals each. Dexmedetomidine (0.01 mg/kg) or 0.9% saline was administered intravenously (D and S, respectively). After 5 min, propofol was administered intravenously and anaesthesia was maintained with sevoflurane. Heart and respiratory rates, arterial blood pressure, oxygen saturation, rectal temperature and the amount of propofol needed for induction were measured. Premedication with dexmedetomidine reduced the requirement of propofol (6.7+/-3.8 mg/kg), but induced bradycardia, compared with the administration of saline (15.1+/-5.1 mg/kg). Recovery quality was significantly better in D but no significant difference in time to return of swallowing reflex was observed between groups (D=2.5+/-0.5 min; S=3.2+/-1.8 min). In conclusion, dexmedetomidine is a safe and effective agent for premedication in cats undergoing propofol-sevoflurane anaesthesia with minimal adverse effects.     

Maintenance of anaesthesia in sheep with isoflurane, desflurane or sevoflurane

Rapid recovery from anaesthesia is advantageous in small ruminants, to reduce the risk of regurgitation. Theoretically, the least soluble inhalation agents should result in the fastest recoveries, but using additional injectable agents may negate this advantage. This study compared three inhalation agents for the maintenance of anaesthesia in sheep. Eighteen ewes that were to undergo orthopaedic surgery were allocated to one of three groups. Each group was premedicated with xylazine (0.1 mg/kg intramuscularly), anaesthesia was induced using ketamine (2 mg/kg) and midazolam (0.03 mg/kg) intravenously and analgesia provided by buprenorphine (0.008 mg/kg intramuscularly). Anaesthesia was then maintained with either isoflurane, sevoflurane or desflurane. Cardiopulmonary parameters were monitored throughout. All three inhalation agents provided adequate stable anaesthesia and there was no significant difference between the groups in their cardiopulmonary parameters or their recovery times. The mead (sd) postanaesthetic times to first swallow, first chewing attempts and ability to maintain their head lifted for five minutes were, respectively, 3.95 (2.53), 6.37 (3.68) and 32.8 (18.1) minutes for isoflurane, 3.62 (0.98), 7.66 (0.78) and 38.8 (16.6) minutes for sevoflurane, and 4.37 (1.65), 6.95 (1.52) and 29.8 (11.5) minutes for desflurane. Two sheep had poor quality recoveries after the use of sevoflurane, but all the other sheep recovered uneventfully. All three inhalation agents were suitable for the maintenance of anaesthesia in sheep but, as used in this study, there were no differences between them in speed of recovery.     

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.     

Effects of different doses of dexmedetomidine on anaesthetic induction with alfaxalone – a clinical trial

ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D₀), 1 μg kg^?1 dexmedetomidine (D₁) intramuscularly (IM) or 3 μg kg^?1 dexmedetomidine IM (D₃). All dogs also received 0.2 mg kg^?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg^?1 minute^?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D₀ 1.68 ± 0.24, D₁ 1.60 ± 0.36 and D₃ 1.41 ± 0.43, the difference between D₀ and D₃ being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg^?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.     

The effects of nitrous oxide on recovery from isoflurane anaesthesia in dogs

O bjectives : To assess rate and quality of recovery from anaesthesia where isoflurane was delivered in oxygen or oxygen/nitrous oxide.
M ethods : Dogs anaesthetised with propofol were randomly allocated to receive isoflurane maintenance in either 100 per cent oxygen (group 1) or 66 per cent nitrous oxide (N₂O)/34 per cent oxygen (group 2). Time from end of anaesthesia to achieving sternal recumbency was recorded. Incidence of adverse behaviours (vocalisation, uncontrolled head movement and restlessness) were assessed. Recovery quality was recorded on a visual analogue scale (VAS) (anchored at 0 with "best possible" recovery and "did not recover" at 100 mm). Age, weight, gender, anaesthetic duration, mean vaporiser setting, VAS scores, recovery times, postoperative temperature and behavioural scores were compared (chi-squared test, Mann-Whitney U test or t -test as appropriate, significance P≤0·05).
R esults : Objective data from 54 dogs were analysed, only VAS data where the observer was unaware of treatment group were used (n=33). Recovery was faster in group 2 dogs (median 10 min [range 4 to 31] compared with 14 minutes [3 to 43] in group 1, P=0·049) with less restlessness (0 [0 to 4] compared with 2 [0 to 4] in group 1, P=0·013) and uncontrolled head movement (0 [0 to 4] compared with 1 [0 to 3] in group 1, P<0·001). However, VAS scores were not statistically different between groups (group 1: mean 39·4 mm [s.d. 24·0)]; group 2: 30·1 mm [25·9]; P=0·303).
C linical S ignificance : Addition of N₂O to isoflurane anaesthesia results in a lower incidence of adverse behaviour (for example restlessness) and marginally faster recovery.     

Influence of oral co-administration of a preparation containing calcium and magnesium and food on enrofloxacin pharmacokinetics

The objective of this study has been to determine the influence of food and ions on the pharmacokinetics of enrofloxacin (ENRO) in turkeys, administered per os at a dose of 10 mg/kg of body weight (b.w.). Co-administration of ENRO with ions or with food significantly retarded its absorption, and the interaction was more pronounced when the drug was given together with food. The bioavailability of ENRO was 65.78 ± 7.81% and 47.99 ± 9.48% with ions and food, respectively. The maximum concentration (C_max) in plasma of animals exposed to ions reached 0.87 ± 0.26 μg/ml in a t_max of 2.07 ± 0.76 h; in animals which were fed while medicated, the analogous parameters were 0.36 ± 0.13 μg/ml and 8.06 ± 3.08 h. The PK/PD analysis demonstrated that a decrease in the concentration of ENRO in turkeys’ blood due to the interaction with ions or food might impair the drug's clinical efficacy toward some pathogenic microorganisms in turkeys if a routine dose of 10 mg ENRO/kg b.w. is administered.     

Effect of combinations of morphine,dexmedetomidine and maropitant on the electroencephalogram in response to acute electrical stimulation in anaesthetized dogs

This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p < .05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra-additive interaction between these two drugs.     

Comparison between dexmedetomidine and acepromazine in combination with methadone for premedication in brachycephalic dogs undergoing surgery for brachycephalic obstructive airway syndrome

ObjectiveTo compare dexmedetomidine with acepromazine for premedication combined with methadone in dogs undergoing brachycephalic obstructive airway syndrome (BOAS) surgery.Study designRandomized, blinded clinical study.AnimalsA group of 40 dogs weighing mean (± standard deviation) 10.5 ± 6 kg, aged 2.6 ± 1.9 years.MethodsDogs received either acepromazine 20 μg kg^–1 (group A) or dexmedetomidine 2 μg kg^–1 (group D) intramuscularly with methadone 0.3 mg kg^–1. Anaesthesia was induced with propofol and maintained with sevoflurane. Sedation (0–18), induction (0–6) and recovery (0–5) qualities were scored. Propofol dose, hypotension incidence, mechanical ventilation requirement, extubation time, additional sedation, oxygen supplementation, regurgitation and emergency intubation following premedication or during recovery were recorded. Data were analysed using t tests, Mann-Whitney U or Chi-square tests.ResultsGroup A dogs were less sedated [median (range): 1.5 (0–12)] than group D [5 (1–18)] (p = 0.021) and required more propofol [3.5 (1–7) versus 2.4 (1–8) mg kg^–1; p = 0.018]. Induction scores [group A: 5 (4–5); group D 5 (3–5)] (p = 0.989), recovery scores [group A 5 (4–5); group D 5(3–5)](p = 0.738) and anaesthesia duration [group A:93 (50–170); group D 96 (54–263) minutes] (p = 0.758) were similar between groups. Time to extubation was longer in group A 12.5 (3-35) versus group D 5.5 (0–15) minutes; (p = 0.005). During recovery, two dogs required emergency intubation (p > 0.99) and five dogs required additional sedation (p > 0.99). Oxygen supplementation was required in 16 and 12 dogs in group A and D, respectively (p = 0.167); no dogs in group A and one dog in group D regurgitated (p = 0.311).Conclusions and clinical relevanceDexmedetomidine 2 μg kg^–1 produces more sedation but similar recovery quality to acepromazine 20 μg kg^–1 combined with methadone in dogs undergoing BOAS surgery.     

Pharmacokinetics of dexmedetomidine,MK‐467, and their combination following intravenous administration in male cats

This study characterized the pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous bolus administration to cats. Seven 6‐ to‐year‐old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK‐467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK‐467 [75, 150, 300 or 600 μg/kg—only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two‐compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half‐life (min) were 342 (131–660), 829 (496–1243), 14.6 (9.6–22.7) and 48 (40–69) for D12.5; 296 (179–982), 1111 (908–2175), 18.2 (12.4–22.9) and 52 (40–76) for D25; 653 (392–927), 1595 (1094–1887), 22.7 (18.5–36.4) and 48 (35–60) for dexmedetomidine in D25M600; 117 (112–163), 491 (379–604), 3.0 (2.0‐4.5) and 122 (99‐139) for M300; and 147 (112‐173), 462 (403‐714), 2.8 (2.1–4.8) and 118 (97–172) for MK‐467 in D25M600. MK‐467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK‐467.     

Two doses of dexmedetomidine in combination with buprenorphine for premedication in dogs; a comparison with acepromazine and buprenorphine

ObjectiveTo assess as premedicants, the sedative, cardiorespiratory and propofol-sparing effects in dogs of dexmedetomidine and buprenorphine compared to acepromazine and buprenorphine.Study designProspective, randomised, blinded clinical studyAnimalsSixty healthy dogs (ASA grades I/II). Mean (SD) body mass 28.0 ± 9.1 kg, and mean age 3.4 ± 2.3 years.MethodsDogs were allocated randomly to receive 15 μg kg^?1 buprenorphine combined with either 30 μg kg^?1 acepromazine (group 1), 62.5 μg m^?2 dexmedetomidine (group 2), or 125 μg m^?2 dexmedetomidine (group 3) intramuscularly. After 30 minutes, anaesthesia was induced using a propofol target controlled infusion. Heart rate, respiratory rate, and oscillometric arterial blood pressure were recorded prior to induction, at endotracheal intubation and at 3 and 5 minutes post-intubation. Induction quality and pre-induction sedation were scored on 4 point scales. Propofol target required for endotracheal intubation was recorded. Data were analysed using Chi-squared tests, Kruskal-Wallis, one way and general linear model anova (p < 0.05).ResultsAge was significantly lower in group 1 (1.0 (1.0–3.8) years) than group 2 (5.0 (2.0–7.0) years), (median, (IQR)). There were no significant differences in sedation or quality of induction between groups. After premedication, heart rate was significantly lower and arterial blood pressures higher in groups 2 and 3 than group 1, but there was no significant difference between groups 2 and 3. Propofol targets were significantly lower in group 3 (1.5 (1.0–2.5) μg mL^?1) than group 1 (2.5 (2.0–3.0) μg mL^?1); no significant differences existed between group 2 (2.0 (1.5–2.5) μg mL^?1) and the other groups (median, (interquartile range)).Conclusions and Clinical relevanceWhen administered with buprenorphine, at these doses, dexmedetomidine had no advantages in terms of sedation and induction quality over acepromazine. Both doses of dexmedetomidine produced characteristic cardiovascular and respiratory effects of a similar magnitude.