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Objective: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels., Study Design: Prospective, placebo-controlled, blinded, experimental trial., Animals: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months., Methods: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 μg kg -1 orally and placebo IV; TMP: tasipimidine 30 μg kg -1 orally and methadone 0.2 mg kg -1 IV; and TMPD: tasipimidine 30 μg kg -1 orally with methadone 0.2 mg kg -1 and dexmedetomidine 1 μg kg -1 IV followed by 1 μg kg -1 hour -1 . Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO 2 ) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05., Results: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO 2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine., Conclusions and Clinical Relevance: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia., Study Design: Placebo-controlled, randomized, blinded, experimental trial., Animals: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months., Methods: The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 μg kg -1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 μg kg -1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg -1 IV. TMPD: tasipimidine 30 μg kg -1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg -1 and dexmedetomidine 1 μg kg -1 IV followed by a dexmedetomidine constant rate infusion of 1 μg kg -1 hour -1 . Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MAC NM ) were determined. A mixed-model analysis or the Friedman and Mann-Whitney test were used; p-value < 0.05., Results: Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MAC NM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MAC NM was reduced by 35%., Conclusions and Clinical Relevance: An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The study aimed to evaluate the applicability and repeatability of cold stimulation in dogs., Animals: 10 healthy Beagle dogs were used in a blinded cross-over experiment., Methods: Measurements were performed in triplicate at 4 skin locations. The probe was manually placed, and temperature decreased (32 to 10 °C) at different cooling rates (0.5, 1, and 5 °C second-1) and latency was measured (11 °C for 60 seconds). Stimulations were discontinued when avoidance reactions were detected. Thermal threshold or time-to-reaction were recorded. Experiments were performed 3 times per animal in weeks 1 (Exp1), 2 (Exp2), and 5 (Exp3). Feasibility of cold stimulation was scored (0-5). Data were analyzed with mixed logistic regression., Results: No significant differences in number of avoidance reactions between cooling-rates were detected. Significantly more reactions (P < .001) were observed during Exp1 compared to Exp2 and Exp3. Thermal thresholds were 13 ± 2.6 °C, 17.7 ± 4 °C and 16.3 ± 4.6 °C for 5, 0.5 and 1 °C second-1, respectively. Latency to the reaction was determinable in 37% of measurements. The mean time-to-reaction was 13 ± 11 seconds. In 85% of measurements, a feasibility score of 0 (best feasibility) was assigned., Clinical Relevance: The method is easily applicable and well tolerated, but habituation could not be excluded. Overall, the aversiveness of cold stimulation in healthy dogs is limited and it is not possible to recommend a specific protocol. In future studies, it needs to be determined if the aversiveness of cold stimulation is increased in diseased dogs.

To study the antinociceptive properties of epidural magnesium sulphate (MgSO 4 ) in standing horses Experimental, placebo-controlled, masked, cross-over A group of six healthy horses Through an epidural catheter, 1 mg kg -1 MgSO 4 (treatment Mg) diluted to a volume of 15 mL or the same volume of saline (treatment S) was administered over 15 minutes. Electrical, thermal and mechanical nociceptive thresholds were determined on the pelvic limb before and 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes after the start of the injection. Heart rate (HR) and respiratory frequency (f R ) were recorded every 10 minutes. Blood samples were collected before treatment and every 30 minutes throughout the study period. Data were assessed for normality using a Shapiro-Wilk test. A linear mixed model with horse as random effect and time, treatment and their interaction as fixed effects was used. Treatments were compared at 20, 60, 120 and 180 minutes using the Wilcoxon rank sum test stratified for horse (global α = 0.05, with Bonferroni correction α = 0.0125). Epidural MgSO 4 caused a significant increase in the electrical threshold (mA) (P = .0001), but no significant differences in thermal and mechanical nociceptive thresholds. During the injection of MgSO 4, two horses collapsed. One stood up within 20 minutes and was able to continue the study, the second one was excluded. A significant difference was found for HR at T180 (Mg 44 ± 23 beats minute -1 ; S 32 ± 9 beats minute -1 ) (P = .0090). Epidural administration of MgSO 4 caused an increase in the electrical threshold of the pelvic limbs of horses. Caution is warranted however, as with the current dose, 2 horses collapsed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A bolus of 50 mg kg -1 MgSO 4 (treatment Mg) or the same volume of saline (treatment S) was infused over 15 minutes in 5 adult healthy horses. T0 was the end of the infusion. Physiological parameters were recorded throughout the study period. Measurements of electrical, thermal, and mechanical nociceptive thresholds were performed at the pelvic limbs at baseline (before T0), and at specific timepoints. Blood samples were taken at fixed timepoints before, during and until 12 hours after the infusion. For statistical analysis, the 95% confidence intervals (CI's) for the differences in nociceptive thresholds between treatments were calculated. Physiological parameters were compared using a linear mixed model (global α = 0.05, with Bonferroni correction α = 0.0125). The concentrations of ions were also compared with the baseline values at specific timepoints, using a linear mixed model. The Pearson's correlation coefficient was derived between the ion concentrations. The 95% CI's of thermal, mechanical and electrical thresholds were [-1; +2]°C, [0; +3] N and [-1; +1] mA (positive differences indicate higher thresholds for treatment Mg), respectively. Heart rate was significantly higher (P < .0001) and non-invasive systolic arterial pressure (P < .0001) and respiratory rate (P = .0002) significantly lower after treatment Mg compared to treatment S. Additionally, non-invasive systolic arterial pressure was significantly different at T45 (P < .001). Although mild changes in cardiovascular parameters and plasma concentrations were seen with intravenous administration of MgSO 4 , no changes in nociceptive thresholds were detected in standing non-sedated horses., (Copyright © 2022. Published by Elsevier Inc.)

Intestinal ischemia reperfusion injury (IRI) is a frequent complication of equine colic. Several mechanisms may be involved in adaptation of the intestinal epithelium to IRI and might infer therapeutic potential, including hypoxia-inducible factor (HIF) 1α, AMP-activated protein kinase (AMPK), nuclear factor-erythroid 2-related factor 2 (NRF2), and induction of autophagy. However, the mechanisms supporting adaptation and thus cellular survival are not completely understood yet. We investigated the activation of specific adaptation mechanisms in both no and low flow ischemia and reperfusion simulated in equine jejunum epithelium in vivo . We found an activation of HIF1α in no and low flow ischemia as indicated by increased levels of HIF1α target genes and phosphorylation of AMPKα tended to increase during ischemia. Furthermore, the protein expression of the autophagy marker LC3B in combination with decreased expression of nuclear-encoded mitochondrial genes indicates an increased rate of mitophagy in equine intestinal IRI, possibly preventing damage by mitochondria-derived reactive oxygen species (ROS). Interestingly, ROS levels were increased only shortly after the onset of low flow ischemia, which may be explained by an increased antioxidative defense, although NFR2 was not activated in this setup. In conclusion, we could demonstrate that a variety of adaptation mechanisms manipulating different aspects of cellular homeostasis are activated in IRI irrespective of the ischemia model, and that mitophagy might be an important factor for epithelial survival following small intestinal ischemia in horses that should be investigated further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dengler, Sternberg, Grages, Kästner and Verhaar.)

Objective: To compare the effects of MK-467 during isoflurane anaesthesia combined with xylazine or dexmedetomidine on global and gastrointestinal perfusion parameters., Study Design: Prospective, randomized experimental trial., Animals: A total of 15 warmblood horses., Methods: Horses were divided into two groups for administration of either dexmedetomidine (D) or xylazine (X) for premedication (D: 3.5 μg kg -1 ; X: 0.5 mg kg -1 ) and as constant rate infusion during isoflurane anaesthesia (D: 7 μg kg -1 hour -1 ; X: 1 mg kg -1 hour -1 ). During anaesthesia, heart rate, mean arterial blood pressure (MAP), systemic vascular resistance index (SVRI) and cardiac index (CI) were measured. Microperfusion of the colon, jejunum and stomach was measured using laser Doppler flowmetry. After 2 hours of stabilization, MK-467 (250 μg kg -1 ) was administered, and measurements were continued for another 90 minutes. For statistical analysis, the permutation test and Wilcoxon rank-sum test were used (p < 0.05)., Results: There were no differences in baseline measurements between groups. The MK-467 bolus resulted in a significant decrease in MAP (D: -58%; X: -48%) and SVRI (D: -68%; X: -65%) lasting longer in group D (90 minutes) compared to group X (60 minutes). While CI increased (D: +31%; X: +35%), microperfusion was reduced in the colon (D: -44%; X: -34%), jejunum (D: -26%; X: -33%) and stomach (D: -37%; X: -35%)., Conclusions and Clinical Relevance: Alpha-2-agonist induced vasoconstriction was reversed by the MK-467 dose used, resulting in hypotension and rise in CI. Gastrointestinal microperfusion decreased, probably as a result of insufficient perfusion pressure. An infusion rate for MK-467 as well as an ideal agonist/antagonist ratio should be determined., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the transdermal local anaesthetic effect of lidocaine or lidocaine combined with prilocaine or tetracaine in horses., Study Design: Experimental, randomized study., Animals: A total of five healthy adult warmblood horses., Methods: Horses were clipped bilaterally at the withers, cranial saddle area and caudal saddle area. Baseline measurements for mechanical superficial sensation via von Frey filaments and nociceptive thermal thresholds were performed. A 5% lidocaine patch (12 hour exposure, treatment L), a lidocaine/prilocaine cream (each 2.5%, treatment LP) and a lidocaine/tetracaine cream (each 7%, treatment LT) were applied (both 2 hour exposure). The same product was applied at the same location bilaterally, but on the right side an epidermal micro-perforation (dermaroller, 1200 needles) was performed prior to application. A total of five more measurements were performed at each location, immediately at the end of exposure time followed by hourly measurements. Thermal thresholds normalized to thermal excursion were analysed. One- or two-way anova and the Wilcoxon signed-rank test were used for statistical analysis with p<0.05 considered significant., Results: Epidermal micro-perforation had no enhancing effect. Treatments L, LP, and LT resulted in increased thermal excursion (%) immediately (84.7±12.9; 100.0±0.0; 100.0±0.0) and 1 hour (81.7±66; 86.0±17.7; 87.7±14.4) after the removal of the respective product compared to baseline (66.1±9.3; 69.9±8.3; 76.5±7.8). Superficial mechanical sensation was decreased by the lidocaine-and-tetracaine cream at all time points, and by the lidocaine patch and lidocaine-and-prilocaine cream for three measurements., Conclusions and Clinical Relevance: Eutectic mixtures of lidocaine with either prilocaine or tetracaine led to a reduction in thermal nociception and mechanical sensation for up to 2 hours., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare alteration in intestinal blood flow in anaesthetized horses with changes in oral mucosa blood flow., Study Design: Prospective, randomized clinical study., Animals: Eight warmblood horses., Methods: After induction with guaifenesin and ketamine, anaesthesia was maintained with isoflurane at 1.5 vol% in oxygen. The tissue blood flow was measured using laser Doppler flowmetry at the jejunum, colon, rectal mucosa, oesophageal mucosa and the oral mucosa. After three baseline measurements, blood flow was first increased by dobutamine infusion and thereafter decreased by increasing isoflurane concentration and all measurements repeated twice. anova was used for comparing the measured parameters to baseline and correlation between the different measurement localizations was examined using Pearson correlation (p < 0.05)., Results: Microperfusion at all measurement sites increased significantly during dobutamine infusion and decreased significantly during high isoflurane concentration. There was a significant correlation between flow at the oral mucosa and flow at the jejunum (r 2  = 0.77, p = 0.002), colon (r 2  = 0.76, p < 0.001), rectal mucosa (r 2  = 0.88, p < 0.001) and oesophageal mucosa (r 2  = 0.83, p <0.001)., Conclusions and Clinical Relevance: Oral mucosa blood flow can be used in isoflurane anaesthetized horses to reflect changes of intestinal microcirculation., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood., Objectives: To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia., Study Design: In vivo randomised crossover experiment., Methods: Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 min, in a randomised order, with a 45 min washout-period. Blood flow and tissue oxygenation (sO 2 ) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated., Results: Compared to baseline high dose dobutamine significantly increased CO, HR, MAP (P<0.001) and blood flow to the jejunum (+47 ± 26%, P = 0.001) and colon (+29 ± 15%, P<0.001) (mean ± s.d.). Dopamine (DA5) increased CO but decreased colonic blood flow (-39 ± 21% from baseline, P<0.001), as well as SVR and MAP compared to baseline (P<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increased MAP and SVR from baseline (P<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow and sO 2 , most profoundly at the colon compared to baseline (flow -44 ± 21%; sO 2 -16 ± 3%, P<0.001), while MAP and SVR increased and CO and HR decreased (P<0.001)., Main Limitations: The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques., Conclusion: At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreased MAP and peripheral perfusion. Noradrenaline increased MAP and SVR while peripheral blood flow was maintained, phenylephrine increased MAP, but reduced both local and systemic perfusion., (© 2017 EVJ Ltd.)

Reasons for Performing Study: High airway pressures, necessary to keep equine lungs open, can have a detrimental impact on central and peripheral perfusion., Objective: The aim of this study was to assess the effects of stepwise increasing airway pressure recruitment on central and intestinal perfusion and oxygenation during isoflurane anaesthesia in horses., Study Design: In vivo experimental study., Methods: Ten anaesthetised horses were ventilated using intermittent positive pressure ventilation immediately after induction. After 90 min, end-expiratory pressure (PEEP) was increased by steps of 5 cmH 2 O every 10 min up to a PEEP of 30 cmH 2 O and decreased back to zero maintaining a constant airway pressure difference of 20 cmH 2 O. Mean arterial blood pressure (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration and cardiac output (thermodilution method) were measured. Cardiac index (CI) was calculated. Arterial blood gases were taken to measure arterial partial oxygen pressure (PaO 2 ) and calculate arterial oxygen saturation (SaO 2 ). Intestinal microperfusion and oxygenation were measured by laser Doppler flowmetry and white-light spectrophotometry. After ventral median laparotomy, a probe was placed on the stomach, jejunum and pelvic flexion of the colon. An ANOVA for repeated measurements and Tukey's post hoc test were used for statistical analysis (α = 5%)., Results: Recruitment of the lungs resulted in a significant increase in PaO 2 from 201 ± 58 mmHg (baseline) to a maximum of 495 ± 75 mmHg. The CI and MAP decreased continuously with increasing airway pressures. When CI and MAP were 37 ± 9 ml/kg/min and 52 ± 8 mmHg (at PEEP of 25 cmH 2 O), respectively, a sudden decrease in intestinal perfusion followed by a delayed decrease in oxygenation occurred., Conclusions: There was linear correlation between airway pressures and CI and MAP but not between central and gastrointestinal perfusion. Despite improvement of arterial oxygenation the decrease in CI and, therefore, in oxygen delivery PEEP resulted in a decrease in gastrointestinal oxygenation., (© 2016 EVJ Ltd.)

In order to develop a long-term anesthesia for flighty antelope species in field situations, two different protocols for induction and maintenance with an intravenous infusion were evaluated in wild-caught impala ( Aepyceros melampus ). Ten adult female impala were induced with two induction protocols: one consisted of 0.2 mg/kg medetomidine, 4 mg/kg ketamine, and 0.15 mg/kg butorphanol (MKB) and one consisted of 0.375 mg/kg etorphine, 0.2 mg/kg medetomidine, and 0.2 mg/kg midazolam (EMM). In both treatments, anesthesia was maintained with a continuous intravenous infusion (CII) at an initial dose rate of 1.2 μg/kg per hr medetomidine, 2.4 mg/kg per hr ketaminen and 36 μg/kg per hr midazolam. Partial reversal was achieved with naltrexone (2 : 1 mg butorphanol; 20 : 1 mg etorphine) and atipamezole (5 : 1 mg medetomidine). Evaluation of anesthesia included respiratory rate, heart rate, rectal temperature, arterial blood pressure, oxygen saturation, end tidal carbon dioxide tension, and tidal volume at 5-min intervals, palpebral reflex and response to painful stimuli at 15-min intervals, and arterial blood gases at 30-min intervals. Plasma cortisol concentration was determined after induction and before reversal. Duration and quality of induction and recovery were evaluated. EMM caused a faster induction of 9.5 ± 2.9 min compared to 11.0 ± 6.4 min in MKB. Recovery was also quicker in EMM (EMM: 6.3 ± 5.4 min; MKB: 9.8 ± 6.0 min). However, EMM also produced more cardiopulmonary side effects, including hypoxemia and hypercapnia, and calculated oxygenation indices (PaCO 2 -PETCO 2 ) were worse than in MKB. One animal died after induction with EMM. The CII provided surgical anesthesia in 7 of 10 animals in MKB and in 9 of 9 animals in EMM for 120 min. In conclusion, the MKB induction protocol had advantages for prolonged anesthesia in impala with significantly less cardiopulmonary depression compared to EMM. The comparably decreased anesthetic depth could easily be adjusted by an increase of the CII.

Objective: Comparison of ultrasound-guided femoral and sciatic nerve block versus epidural anaesthesia with bupivacaine and morphine for orthopaedic surgery of the pelvic limb in dogs with respect to analgesic effectiveness, clinical utility and side effects., Material and Methods: The study included 22 dogs (American Society of Anesthesiologists, ASA grades I and II) undergoing orthopaedic surgery distal to the mid-femoral bone. The study was designed as a randomized, prospective, blinded clinical trial. All dogs were randomly assigned to receive 0.5 mg/kg bupivacaine (0.5%) and 0.1 mg/kg morphine sulphate (1%) either as epidural anaesthesia (group EPI) or by ultrasound-guided femoral and sciatic nerve block (group LA). During surgery, the heart rate, respiratory rate, mean arterial pressure (MAP), end-tidal isoflurane concentrations and dose of rescue analgesia (fentanyl boluses of 5 µg/kg i. v.) were measured. Pain severity was scored (short form of the Glasgow Composite Measure Pain Scale, GCMPS) before surgery and postoperatively at 2, 4, 6, 12 and 24 hours after extubation. Post-operative rescue analgesia consisted of methadone (0.2 mg/kg i. v.), and was applied when the GCMPS > 6. For statistical analysis, the Chi-square, Fisher, and Wilcoxon tests and one- and two-way ANOVA were applied. Differences were considered statistically significant at p < 0.05., Results: Only the MAP was significantly different between the two treatment groups. Intra- and postoperative MAP of group LA (111.2 ± 11.2 mmHg and 119.3 ± 18.2 mmHg, respectively) was higher than in group EPI (86.6 ± 8.7 mmHg and 95.2 ± 13.1 mmHg, respectively). None of the dogs developed urinary retention or ambulatory deficits when completely recovered from anaesthesia. No other side effects were noted., Clinical Relevance: In conclusion, femoral and sciatic nerve blocks and epidural anaesthesia ensure comparable analgesic effects in canine patients undergoing orthopaedic surgery of the pelvic limb. The lower mean arterial blood pressure of group EPI was not of clinical relevance.

The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To investigate possible interactions visible on electroencephalogram recordings caused by concomitant administration of marbofloxacin and carprofen or cimicoxib in dogs without central nervous system disease., Methods: Totally 21 client-owned dogs undergoing different surgeries were included in a randomised, blinded, clinical study. Each dog was assigned to one of two groups treated with either carprofen or cimicoxib pre- and postoperatively. After anaesthetic induction both groups received marbofloxacin intravenously while recording an electroencephalogram. Offline electroencephalogram analysis included qualitative evaluation and Fast Fourier Transformation. Postoperative analgesia was evaluated for 24 hours and after 10 days with the short-form Glasgow Composite Measure Pain Scale. Statistical analysis included Wilcoxon signed rank test, Mann-Whitney U test and Student's t-test with α set at 5%., Results: Marbofloxacin injection caused no effects on quantitative and qualitative electroencephalogram parameters in both groups. No differences in postoperative pain scoring were found between treatment groups., Clinical Significance: Concurrent use of marbofloxacin with either cimicoxib or carprofen did not induce neuroexcitatory activities in dogs without CNS disease directly after administration., (© 2016 British Small Animal Veterinary Association.)

Objective: To investigate the use of the Narcotrend electroencephalogram (EEG) monitor for the assessment of anesthetic depth in horses undergoing xylazine balanced isoflurane anesthesia., Study Design: Blinded experimental study., Animals: Seven healthy warm-blooded horses, aged 10.6 ± 5.9 years, weighing 535 ± 55 kg., Methods: Horses were anesthetized for a terminal surgical trial with xylazine, thiopentone, and guaiphenesin for induction and isoflurane and xylazine continuous rate infusion for maintenance. After surgery, an EEG was recorded and processed by the Narcotrend monitor. It displays an index [Narcotrend index (NI)] between 0 and 100, which is supposed to indicate anesthetic depth. This index was recorded and correlated with eight different end tidal (ET) isoflurane concentrations between 0.8 and 2.2 vol%. In addition, anesthetic depth was numerically scored based on common clinical signs with a score of 1 (plane "too deep") to 4 (plane "too light"). After testing for normal distribution, both clinical scores and NI were correlated with different ET isoflurane concentrations using Spearman rank correlation., Results: Correlation of NI with ET isoflurane concentrations was poor (r s = 0.24). The NI ranged between maximal 48 and minimal 13 in the horses. The clinical scores decreased with increasing ET isoflurane concentrations (r s = 0.80). They ranged from 1 to 4 in different horses at the concentrations investigated., Conclusion: In this study, the NI did not seem to be useful for assessment of anesthetic depth in horses receiving isoflurane anesthesia balanced with a xylazine constant rate infusion.

Objective: To determine the acute anti-nociceptive and the minimal alveolar concentration (MAC) sparing effects of metamizole sodiummonohydrate (dipyrone) in dogs for possible perioperative analgesia., Study Design: Two groups of seven adult dogs were used in two separate randomised, blinded, controlled, cross-over studies. In each study, each dog received metamizole 50 mg kg(-1) intravenously (IV) and placebo (saline 0.9%) IV., Methods: Sevoflurane MAC was determined using the bracketing technique and electrical stimulation (50 V, 50 Hz, 10 milliseconds) at a thoracic limb, before treatment and 1 and 4 hours post treatment. In conscious dogs, thermal thresholds were determined by ramped contact heat at the thoracic wall. Mechanical thresholds (MTs) were measured by constantly rising force pressing against the radial bone. Thresholds were determined pre and 45, 75, 105, 135, 165, 195, 225, 255, 285, 315, 345, 375, 435, 495, 555, 615, 675, 735 minutes and 24 hours post treatment. Parametric data were analyzed by analysis of variance for repeated measurements and paired t-tests. Friedman test was used for nonparametric data. Level of significance was set to <5%., Results: Metamizole did not change MAC of sevoflurane significantly compared to baseline values [mean ± SD Vol%; 2.7 ± 0.5 (BL); 2.8 ± 0.6 (1 hour); 2.8 ± 0.4 (4 hours)] and placebo [2.8 ± 0.5 (BL); 2.9 ± 0.5 (1 hour); 2.9 ± 0.4 (4 hour)]. Metamizole caused a significant rise in % TE up to 105 minutes (66.5 ± 12.1%) and in MT up to 75 minutes (12.7 ± 5.0 N) compared to baseline (55 ± 10%; 7.9 ± 1.8 N). There were no significant differences between treatments., Conclusion and Clinical Relevance: Metamizole did not induce an anaesthetic sparing effect. In awake dogs metamizole induced only mild and short cutaneous anti-nociception. Metamizole as the sole analgesic drug in the perioperative periode is not recommended., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

There is a growing necessity to perform long-term anesthesia in wildlife, especially antelope. The costs and logistics of transporting wildlife to veterinary practices make surgical intervention a high-stakes operation. Thus there is a need for a field-ready total intravenous anesthesia (TIVA) infusion to maintain anesthesia in antelope. This study explored the feasibility of an etorphine-ketamine-medetomidine TIVA for field anesthesia. Ten wild-caught, adult impala ( Aepyceros melampus ) were enrolled in the study. Impala were immobilized with a standardized combination of etorphine (2 mg) and medetomidine (2.2 mg), which equated to a median (interquartile range [IQR]) etorphine and medetomidine dose of 50.1 (46.2-50.3) and 55.1 (50.8-55.4) μg/kg, respectively. Recumbency was attained in a median (IQR) time of 13.9 (12.0-16.5) min. Respiratory gas tensions, spirometry, and arterial blood gas were analyzed over a 120-min infusion. Once instrumented, the TIVA was infused as follows: etorphine at a variable rate initiated at 40 μg/kg per hour (adjusted according to intermittent deep-pain testing); ketamine and medetomidine at a fixed rate of 1.5 mg/kg per hour and 5 μg/kg per hour, respectively. The etorphine had an erratic titration to clinical effect in four impala. Arterial blood pressure and respiratory and heart rates were all within normal physiological ranges. However, arterial blood gas analysis revealed severe hypoxemia, hypercapnia, and acidosis. Oxygenation and ventilation indices were calculated and highlighted possible co-etiologies to the suspected etorphine-induced respiratory depression as the cause of the blood gas derangements. Impala recovered in the boma post atipamezole (13 mg) and naltrexone (42 mg) antagonism of medetomidine and etorphine, respectively. The etorphine-ketamine-medetomidine TIVA protocol for impala may be sufficient for field procedures of up to 120-min duration. However, hypoxemia and hypercapnia are of paramount concern and thus oxygen supplementation should be considered mandatory. Other TIVA combinations may be superior and warrant further investigation.

The aim of this study was to assess the effect of duration of anaesthesia and concentration of isoflurane on global perfusion as well as intestinal microperfusion and oxygenation. Nine Warmblood horses were premedicated with xylazine; anaesthesia was induced with midazolam and ketamine, and maintained with isoflurane. Horses were ventilated to normocapnia. During 7 h of anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso) and cardiac output using lithium dilution were measured; cardiac index (CI) was calculated. Intestinal microperfusion and oxygenation were measured using laser Doppler flowmetry and white-light spectrophotometry. Surface probes were placed via median laparotomy on the serosal and mucosal site of the jejunum and the pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to 40 ± 5 mL/kg/min and 52 ± 8 mmHg, respectively. Microperfusion and oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of 48 ± 5 mL/kg/min and 62 ± 6 mmHg, respectively, and then decreased rapidly. When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation recovered to baseline. Isoflurane concentration but not duration of isoflurane anaesthesia influenced central and intestinal oxygenation and perfusion in healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved until a threshold MAP or blood flow was reached., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine the agreement of high definition oscillometry (HDO) with direct arterial blood pressure measurements in normotensive, hypotensive and hypertensive horses during general anaesthesia., Study Design: Experimental study., Animals: Seven healthy warmblood horses, aged 3-11 years, weighing 470-565 kg., Methods: Measurements from a HDO device with the cuff placed around the base of the tail were compared with pressures measured invasively from the facial artery. High blood pressures were induced by intravenous (IV) administration of dobutamine (5 μg kg(-1) minute(-1)) over ten minutes followed by norepinephrine (0.1 mg kg(-1) IV) and low pressures by increasing the inspired fraction of isoflurane and administration of nitroglycerine (0.05 mg kg(-1) IV). For analysis three pressure levels were determined: high (MAP>110 mmHg), normal (60 mmHg

Objective: Previous studies showed an influence of xylazine on the LiDCO sensor in vitro and in standing horses, but did not prove that this interaction caused error in LiDCO measurements. Therefore, agreement of cardiac output (CO) measurements by LiDCO and bolus-thermodilution (BTD) was determined in horses receiving xylazine infusions., Study Design: Prospective, experimental study., Animals: Eight Warmblood horses., Methods: All horses were premedicated with xylazine. Anaesthesia was induced with midazolam and ketamine and was maintained with isoflurane in oxygen. During six hours of anaesthesia CO measurements and blood samples were taken before, during and after a 60 minute period of xylazine infusion. Pairs of LiDCO and bolus thermo-dilution (BTD) measurements of CO were performed. Sensor voltages exposed to blood and saline were measured before, during and after xylazine infusion and compared using Bland-Altman method of agreement with corrections for repeated measures., Results: The CO values (mean ± SD) before xylazine were 34.8 ± 7.3 and 36.4 ± 8.1 L minute(-1) for BTD and LiDCO, respectively. After starting the xylazine infusion, the CO values for BTD decreased to 27.5 ± 6.1 L minute(-1) whereas CO values measured by LiDCO increased to 54.7 ± 18.4 L minute(-1) . One hour after discontinuing xylazine infusion, CO values were 33 ± 6.7 and 36.5 ±11.9 L minute(-1) for BTD and LiDCO, respectively. The difference between saline and blood exposed sensor voltages decreased during xylazine infusion and these differences were positive numbers before but negative during the infusion. There were correlations between xylazine plasma concentrations, CO differences and sensor voltage differences (saline - blood)., Conclusions and Clinical Relevance: This study proved that xylazine infusion caused concentration dependent bias in LiDCO measurements leading to an overestimation of readings. Sensor voltage differences (saline - blood) may become valuable clinical tool to predict drug-sensor interactions., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: Evaluation of heart-rate variability (HRV) as an indicator for autonomous activity to monitor anaesthesia in dogs during three different total intravenous anaesthetic protocols and three anaesthetic depth levels as well as before and after electrical nociceptive stimulation., Material and Methods: Seven beagle dogs (14.3±1.7 kg) were used in a randomised experimental trial with a complete cross-over design. Each dog went through all three anaesthetic protocols, which were propofol alone (group P) and propofol combined with dexmedetomidine (3 µg/kg/h, group PD) or remifentanil (18 µg/kg/h, group PR). Propofol was given using target-controlled infusion. Three anaesthetic depth levels (light, medium, deep) were defined by target concentrations for propofol in the blood and were adapted to the individual animal and treatment (mean of 7, 9 and 11 µg/ml, and in combination with dexmedetomidine or remifentanil, a mean of 3, 5 and 7 µg/ml). During each anaesthetic level, a standardised supramaximal nociceptive electric stimulus (50 Hz, 50 V, 10 ms) was applied medially to the right forearm. The bipolar-derived electrocardiogram (ECG) was recorded continuously. For each anaesthetic depth, the RR-intervals recorded 2 minutes before and after each stimulation were included in the statistical analysis. Using an HRV analytical program (Kubios HRV), the frequency domain HRV-parameters low (LF) and high (HF) frequency and the time-domain HRV-parameters RR-intervals, standard deviation of all RR-intervals (SDNN) and the square root of the mean of the sum of the squares of the differences between consecutive RR-intervals (RMSSD) were determined., Results: Neither the RR-intervals nor the currently available HRV-parameters which were derived from the RR-intervals were able to discriminate between the different anaesthetic depths levels. Nociception could only be represented by the RR-intervals., Conclusion: Overall, the investigated standard HRV parameters offered no additional information for the monitoring of anaesthetic depths at the investigated, clinically used dose rates.

In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer's disease-like pathologies in the aging brain.

Objective: To evaluate the use of a micro-lightguide tissue spectrophotometer for measurement of tissue oxygenation and blood flow in the small and large intestines of horses under anesthesia., Animals: 13 adult horses without gastrointestinal disease., Procedures: Horses were anesthetized and placed in dorsal recumbency. Ventral midline laparotomy was performed. Intestinal segments were exteriorized to obtain measurements. Spectrophotometric measurements of tissue oxygenation and regional blood flow of the jejunum and pelvic flexure were obtained under various conditions that were considered to have a potential effect on measurement accuracy. In addition, arterial oxygen saturation at the measuring sites was determined by use of pulse oximetry., Results: 12,791 single measurements of oxygen saturation, relative amount of hemoglobin, and blood flow were obtained. Errors occurred in 381 of 12,791 (2.98%) measurements. Most measurement errors occurred when surgical lights were directed at the measuring site; covering the probe with the surgeon's hand did not eliminate this error source. No measurement errors were observed when the probe was positioned on the intestinal wall with room light, at the mesenteric side, or between the mesenteric and antimesenteric side. Values for blood flow had higher variability, and this was most likely caused by motion artifacts of the intestines., Conclusions and Clinical Relevance: The micro-lightguide spectrophotometry system was easy to use on the small and large intestines of horses and provided rapid evaluation of the microcirculation. Results indicated that measurements should be performed with room light only and intestinal motion should be minimized.

Background: Aim of the study was to compare the effect of neuroleptic sedation with acepromazine and neuroleptanalgesia with acepromazine and buprenorphine on thermal thresholds (TT) obtained at the nostrils and at the withers. The study was carried out as a randomized, blinded, controlled trial with cross-over design. Thermal thresholds were determined by incremental contact heat applied to the skin above the nostril (N) or the withers (W). Eleven horses were treated with saline (S), acepromazine (0.05 mg/kg) (ACE) or acepromazine and buprenorphine (0.0075 mg/kg) (AB) intravenously (IV). Single stimulations were performed 15 minutes prior and 15, 45, 75, 105, 165, 225, 285, 405 and 525 minutes after treatment. Sedation score, gastrointestinal auscultation score and occurrence of skin lesions were recorded. Data were analysed with analysis of variance for repeated measurements., Results: There were no significant differences in TT between N and W with all treatments. The TT remained constant after S and there was no difference in TT between S and ACE. After AB there was a significant increase above baseline in TT until 405 minutes after treatment. Restlessness occurred 30-90 minutes after AB in 7 horses. All horses had reduced to absent borborygmi after AB administration for 165 to 495 minutes., Conclusion: Thermal stimulation at both described body areas gives comparable results in the assessment of cutaneous anti-nociception in horses. There is no differential influence of neuroleptic sedation or neuroleptanalgesia on TTs obtained at N or W. Buprenorphine combined with acepromazine has a long lasting anti-nociceptive effect associated with the typical opioid induced side effects in horses.

Objective: To evaluate the influence of 3 anesthetic protocols and multiples of minimum alveolar concentration (MAC) on heart rate variability (HRV) with and without nociceptive stimulation in dogs., Animals: 6 healthy adult Beagles., Procedures: Each dog was anesthetized 3 times: with isoflurane alone, with isoflurane and a constant rate infusion of dexmedetomidine (IsoD; 3 μg/kg/h, IV), and with isoflurane and a constant rate infusion of remifentanil (IsoR; 18 μg/kg/h, IV). Individual MAC was determined via supramaximal electrical stimulation. Sinus rhythm-derived intervals between 2 adjacent R-R intervals were exported from ECG recordings. Selected HRV time and frequency domain variables were obtained (at 2-minute intervals) and analyzed offline with signed rank tests before and after stimulation at 0.75, 1.0, and 1. 5 MAC for each anesthetic session., Results: The isoflurane session had the overall lowest prestimulation SDNN (SD of all R-R intervals) values. Prestimulation SDNN values decreased significantly with increasing MAC in all sessions. For the IsoD session, SDNN (milliseconds) or high-frequency power (milliseconds(2)) was inversely correlated with MAC (Spearman rank correlation coefficient for both variables, -0.77). In the isoflurane and IsoR sessions, heart rate increased significantly after stimulation. In the IsoD session, poststimulation SDNN was increased significantly, compared with prestimulation values, at 0.75 and 1.0 MAC., Conclusions and Clinical Relevance: On the basis of SDNN and high-frequency power values, anesthetic levels between 0.75 and 1.5 MAC within the same anesthetic protocol could be differentiated, but with a large overlap among protocols. Usefulness of standard HRV variables for assessment of anesthetic depth and nociception in dogs is questionable.

Background: The aim of the study was to evaluate the performance of contact heat thermal stimulation in horses at different body sites and under different environmental conditions and different test situations. Five warm-blood horses were equipped with the thermal probe located on the skin of nostril (N), withers (W) or coronary band (C). Skin temperature and reaction temperature (thermal threshold) at each location were measured and percent thermal excursion (% TE = 100 * (threshold temperature - skin temperature)/(cut-out temperature - skin temperature) was calculated. Environmental conditions were changed in partial random order for all locations, so each horse was tested in its familiar box stall and stocks, in the morning and evening and at warm and cold ambient temperatures. Type of reaction to the stimulus and horse's general behaviour during stimulation were recorded. The stimulation sites were examined for the occurrence of possible skin lesions., Results: Skin temperatures were significantly different during warm and cold ambient temperatures at all three locations, but remained constant over repeated stimulation. An obvious response to stimulation before reaching cut-out temperature could be detected most frequently at N and W in boxes during warm ambient temperatures. The most frequent type of reaction to thermal stimulation at the nostril was headshaking (64.6%), skin twitching at the withers (82.9%) and hoof withdrawal at the coronary band (79.2%)., Conclusion: The outcome of thermal threshold testing depended on ambient temperature, stimulation site and environment. Best results with the WTT2 in horses were obtained at the nostrils or withers in a familiar environment at warm ambient temperatures.

The aim of this study was to assess agreement and repeatability of four ultrasound methods for measuring stroke volume (SV) and cardiac output (CO) in cats. Measurement of SV and CO was performed by the Teichholz method, the Simpson's method (SM), the area length method (ALM) and a volumetric flow method across the aorta (Trace method). For each method, the coefficient of variation (CV) was calculated and agreement was determined by Bland-Altman analysis. The CV was acceptable (<20%) for all parameters, except for SV and CO obtained by SM (28.8% and 22.4%, respectively) and ALM (21.6% and 22.6%, respectively). Narrow limits of agreement were observed between both planimetric methods (SM and ALM). The Trace method was the most repeatable, followed by the Teichholz method. Despite excellent inter-method agreement, neither of the planimetric methods produced results with adequate repeatability. As the Teichholz and Trace methods were acceptably repeatable, and probably gave the most representative values, they appear to be the most useful methods for the measurement of SV and CO in cats. Further investigations are needed to compare the echocardiographic methods described here with a standard technique such as thermodilution., (Copyright © 2012. Published by Elsevier Ltd.)

Objective: To assess the effect of adjunctive gabapentin (GBP) on pain after thoracolumbar intervertebral disc surgery in dogs., Study Design: Prospective, randomized, controlled, clinical, 'blinded' trial., Animals: Sixty-three client owned dogs undergoing hemilaminectomy, Methods: Dogs were assigned to two treatment groups. The GBP group received gabapentin 10 mg kg(-1) orally every 12 hours starting before anaesthesia; the placebo (P) group received empty gelatin capsules. Background analgesia was initiated with intravenous levomethadone 0.6 mg kg(-1) (as the combination 'L-Polamivet) at anaesthesia induction, followed by a fentanyl patch and levomethadone 0.2 mg kg(-1) subcutaneously every 8 hours for 24 hours. Pain was assessed by the short form of the Glasgow Composite Measure Pain Score (CMPS-SF) without the gait category, and by a Visual Analogue Scale (VAS). Serum GBP concentrations and cortisol concentrations were measured. Statistical analyses utilized chi square test, Kolmogorov-Smirnov test, two-way analysis of variances for repeated measurements, Wilcoxon test and Friedmann test as relevant. Correlations were tested by Spearman's and Pearson's correlation coefficient. p < 0.05 was considered significant., Results: Median CMPS-SF was lower in group GBP than in group P on days 0.5, 1, 4 and 5. However, CMPS-SF and VAS were not significantly different between groups. Both pain scores decreased significantly over time. Cortisol concentrations were not significantly different between groups. Minimum serum concentrations of GBP fell below the detection limit of 1 μg mL(-1) in 6 of 29 and 7 of 28 dogs at 24 and 72 hours, respectively., Conclusions and Clinical Relevance: 10 mg kg(-1) GBP orally twice a day did not result in a detectable reduction in pain behaviour compared to background opioid analgesia alone, although a trend to lower pain levels (p < 0.1) was present. Further studies are needed to determine if this is related to effective background analgesia or an ineffective dose of GBP., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Background: In this methodology article a thermal threshold testing device designed to test nociception in cats was assessed in six dogs. The purpose of this study was to investigate baseline reproducibility of thermal thresholds obtained by the contact heat testing device, to assess the influence of acepromazine and levomethadone and fenpipramide in dogs. The relationship between change in nociceptive thermal threshold and the opioid's plasma concentration was determined. Six adult beagle dogs received levomethadone (0.2 mg/kg), acepromazine (0.02 mg/kg) or saline placebo by intramuscular injection (IM) in a randomized cross-over design. Three baseline nociceptive thermal threshold readings were taken at 15 minutes intervals prior to treatment. Further readings were made at 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420 and 480 minutes after injection. A sedation score was assigned at every reading. Four saline placebo treatments were performed to assess baseline reproducibility. Levomethadone serum concentrations were measured prior and 0.5, 1, 2, 4, 8, 12 and 24 hours after drug dosing in a separate occasion., Results: Acepromazine did not seem to increase the thermal threshold at any time. After levomethadone there was a significant rise of the thermal threshold between 15 to 120 minutes at serum concentrations between 22.6-46.3 ng/mL. Baseline reproducibility was stable in adult beagle dogs., Conclusion: The thermal threshold testing system is a suitable device for nociceptive threshold testing in dogs.

Objective: To determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs., Study Design: Prospective, randomized, experimental crossover study., Animals: Five adult healthy Beagle dogs (one male and four females, weighing 12.8-16.4 kg)., Methods: Dogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg(-1) acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg(-1) L-methadone/ 0.025 mg kg(-1) fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant., Results: Baseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP., Conclusions and Clinical Relevance: In healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

The diagnostic value of interictal short time electroencephalographic (EEG) recordings in epileptic dogs under general anaesthesia with propofol and the muscle relaxant rocuronium bromide was investigated. Two activation techniques, namely photic stimulation and hyperventilation, were evaluated for their potential to enhance the diagnostic validity of these recordings. Sixty-one dogs suffering from idiopathic epilepsy and 28 dogs suffering from symptomatic epilepsy were included. Electroencephalograms were recorded using five subdermal EEG electrodes (F3, F4, Cz, O1 and O2). All 89 EEGs were analysed visually and 61 were also evaluated quantitatively with fast Fourier transformation. Interictal paroxysmal epileptiform activity was found in 25% of idiopathic and in 29% of symptomatic epileptic dogs. Quantitative analysis of the EEGs (qEEGs) detected significant differences of frequency analysis in single reading points without any continuous changes of frequency bands. A comparison between healthy and affected brain hemispheres in seven dogs with focal lesions of one hemisphere did not show any significant differences in qEEG analysis. qEEG was not more sensitive than visual evaluation. Despite the use of activation techniques, the results showed that short time EEG recordings in epileptic dogs can detect interictal epileptic activity in less than one third of all seizuring dogs and is not a useful screening method., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the influence of various anesthetic protocols and 3 multiples of isoflurane minimum alveolar concentration (MAC) before and after supramaximal stimulation on electroencephalographic (EEG) variables in dogs., Animals: 6 healthy adult Beagles (mean ± SD body weight, 16.3 ± 1.0 kg)., Procedures: All dogs underwent 3 anesthesia sessions with a minimum of 1 week separating sessions: isoflurane alone, isoflurane and a constant rate infusion of dexmedetomidine (3 μg/kg/h, IV; ID), and isoflurane and a constant rate infusion of remifentanil (18 μg/kg/h, IV; IR). The MAC of isoflurane was determined via supramaximal electrical stimulation. Quantitative variables (frequency bands and their ratios, median frequency, 95% spectral edge frequency [SEF], and an EEG index) were determined directly before and after supramaximal stimulation at 0.75, 1.0, and 1.5 times the MAC for each session of 20-second epochs., Results: Mean ± SD isoflurane MACs for isoflurane alone, ID, and IR were 1.7 ± 0.3%, 1.0 ± 0.1%, and 1.0 ± 0.1%, respectively. Prestimulation 95% SEF decreased significantly with increasing MAC during the isoflurane alone and ID sessions. Significant decreases in δ frequency band (0.5 to 3.5 Hz) presence and significant increases in β frequency band (> 12.5 Hz) presence, median frequency, and 95% SEF after stimulation were dependent on the MAC and anesthetic protocol. The EEG index had the strongest correlation with increasing MAC during the isoflurane-alone session (ρ = -0.89) and the least in the IR session (ρ = -0.15)., Conclusions and Clinical Relevance: Anesthesia with isoflurane alone resulted in the greatest overall EEG depression of all protocols. Use of remifentanil depressed the EEG response to nociceptive stimulation more strongly than did dexmedetomidine. The EEG variables evaluated did not appear useful when used alone as indicators of anesthetic depth in dogs.

The current study evaluated the diagnostic value of electroencephalographic recordings (EEG) in cats with epilepsy under special consideration of photic stimulation and hyperventilation. EEGs in six healthy cats were recorded under light (mean dose of 0.23 mg/kg/min) and deep (mean dose of 0.7 mg/kg/min) propofol anaesthesia, whereas EEGs in 13 diseased cats were recorded under a propofol anaesthesia which was kept as light as possible (mean dose of 0.39 mg/kg/min). Paroxysmal discharges were detected in six of 13 cats suffering from seizures (two cats with idiopathic epilepsy and four cats with symptomatic epilepsy). Activation techniques did not enhance the diagnostic value of the EEGs. Photic driving was detected in one of six healthy cats under light, in five of six healthy cats under deep propofol anaesthesia and in 11 of 13 cats with seizures. Systematic use of activation techniques does not seem to increase the diagnostic yield of the recorded EEGs and should not be used in a clinical setting until future studies indicate value. Further investigations into the origin of photic driving under propofol anaesthesia are needed and could lead to the development of a reliable animal model to research into drug effects on the EEG.

Objective: To compare three anaesthetic protocols for umbilical surgery in calves regarding adequacy of analgesia, and cardiopulmonary and hormonal responses., Study Design: Prospective, randomised experimental study., Animals: Thirty healthy German Holstein calves (7 female, 23 male) aged 45.9 ± 6.4 days., Methods: All calves underwent umbilical surgery in dorsal recumbency. The anaesthetic protocols were as follows: group INH (n = 10), induction 0.1 mg kg(-1) xylazine IM and 2.0 mg kg(-1) ketamine IV, maintenance isoflurane in oxygen; Group INJ (n = 10), induction 0.2 mg kg(-1) xylazine IM and 5.0 mg kg(-1) ketamine IV, maintenance 2.5 mg kg(-1) ketamine IV every 15 minutes or as required; group EPI (n = 10), high volume caudal epidural anaesthesia with 0.2 mg kg(-1) xylazine diluted to 0.6 mL kg(-1) with procaine 2%. All calves received peri-umbilical infiltration of procaine and pre-operative IV flunixin (2.2 mg kg(-1) ). Cardiopulmonary variables were measured at preset intervals for up to 2 hours after surgery. The endocrine stress response was determined. Intra-operative nociception was assessed using a VAS scale. Data were compared between groups using appropriate statistical tests. A value of p < 0.05 was considered significant., Results: All three protocols provided adequate anaesthesia for surgery although, as judged by the VAS scale, intra-operative response was greatest with INJ. Lowest mean cortisol levels during surgery occurred in EPI. Heart rate and cardiac output did not differ between groups, but mean arterial blood pressure, systemic vascular resistance, and partial pressure of carbon dioxide were higher and arterial pH lower in groups INH and INJ than in Group EPI. Group INJ became hypoxaemic and had a significantly greater vascular shunt than did the other groups., Conclusion and Clinical Relevance: Groups INH and EPI both proved acceptable protocols for calves undergoing umbilical surgery, whilst INJ resulted in variable anti-nociception and in hypoxaemia. High volume caudal epidural anaesthesia provides a practical inexpensive method of anaesthesia for umbilical surgery., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats., Study Design: Experimental randomized 'blinded' cross-over study., Animals: Six healthy cats., Materials and Methods: Treatments were administered intramuscularly: midazolam 0.4 mg kg(-1) and butorphanol 0.4 mg kg(-1) (MB); midazolam 0.4 mg kg(-1), butorphanol 0.4 mg kg(-1) and ketamine 3 mg kg(-1) (MBK); midazolam 0.4 mg kg(-1), butorphanol 0.4 mg kg(-1) and dexmedetomidine 5 μg kg(-1) (MBD); ketamine 3 mg kg(-1) and dexmedetomidine 5 μg kg(-1) (KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant., Results: The lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%)., Conclusions and Clinical Relevance: The MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Unlabelled: Objective of this clinical study was to assess the anaesthetic quality (induction and recovery) and utility of short term alfaxalone anaesthesia in healthy and diseased cats. Cardiopulmonary effects and the influence on haematological and biochemical blood parameters were evaluated., Material and Methods: Twenty feline patients (ASA1-4) were anaesthetized with alfaxalone for various short surgical or diagnostic procedures. Heart rate, breathing rate, end-tidal CO2 partial pressure, arterial oxygen saturation, mean arterial blood pressure and the body temperature were measured and recorded every 10 minutes. Before, after and 6 hours after anaesthesia venous blood samples were taken and haematologic and blood chemistry parameters were determined. Recovery time and quality were assessed by a numerical rating scale., Results: Anaesthetic induction was rapid and smooth in all cats. Spontaneous respiration was maintained in all cats. Cardiopulmonary parameters mostly remained within a clinically tolerable range. Noticeable was a high heart rate (mean >190 bpm) at the beginning of anaesthesia lasting up to 10 minutes. Statistically significant changes (p<0.05) occurred in some haematologic parameters (RBC, haemoglobin, haematocrit and MCV decreased), electrolytes and venous acid-base-status (bicarbonate, chloride and base excess increased, sodium and potassium decreased) and blood chemistry parameters (alanine aminotransferase, glutamate dehydrogenase and creatinine decreased). None of these changes appeared to have clinical relevance. Recovery was smooth in the majority of cats. Mild signs of hyperexcitability (muscle tremor, short term opisthotonus and hyperacusis) occurred in individual animals. The duration of recovery varied between 21 and 93 minutes., Conclusion and Clinical Relevance: Alfaxalone by repeated intravenous injection is suitable for short-term diagnostic and surgical procedures in cats. Because of its minor cardiovascular effects and slight respiratory depression, it is also well tolerated by patients with increased anaesthetic risk (ASA 3 and 4).

Objective: To compare, ventilation using intermittent positive pressure ventilation (IPPV) with constant positive end-expiratory pressure (PEEP) and alveolar recruitment manoeuvres (RM) to classical IPPV without PEEP on gas exchange during anaesthesia and early recovery., Study Design: Prospective randomized study., Animals: Twenty-four warm-blood horses, weight mean 548 ± SD 49 kg undergoing surgery for colic., Methods: Premedication, induction and maintenance (isoflurane in oxygen) were identical in all horses. Group C (n = 12) was ventilated using conventional IPPV, inspiratory pressure (PIP) 35-45 cmH2O; group RM (n = 12) using similar IPPV with constant PEEP (10 cmH2O) and intermittent RMs (three consecutive breaths PIP 60, 80 then 60 cmH2O, held for 10-12 seconds). RMs were applied as required to maintain arterial oxygen tension (PaO2) at >400 mmHg (53.3 kPa). Physiological parameters were recorded intraoperatively. Arterial blood gases were measured intra- and postoperatively. Recovery times and quality of recovery were measured or scored., Results: Statistically significant findings were that horses in group RM had an overall higher PaO2 (432 ± 101 mmHg) than those in group C (187 ± 112 mmHg) at all time points including during the early recovery period. Recovery time to standing position was significantly shorter in group RM (49.6 ± 20.7 minutes) than group C (70.7 ± 24.9). Other measured parameters did not differ significantly. The median (range) of number of RMs required to maintain PaO2 above 400 mmHg per anaesthetic was 3 (1-8)., Conclusion: Ventilation using IPPV with constant PEEP and RM improved arterial oxygenation lasting into the early recovery period in conjunction with faster recovery of similar quality. However this ventilation mode was not able to open up the lung completely and to keep it open without repeated recruitment., Clinical Relevance: This mode of ventilation may provide a clinically practicable method of improving oxygenation in anaesthetized horses., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

This study was performed to improve a standard anesthetic protocol for electroencephalography (EEG) in dogs and to evaluate the effect of photic stimulation and hyperventilation on the EEG of healthy dogs. Ten clinically and neurologically normal beagle dogs were anesthetized with propofol given intravenously with average doses of 7.5mg/kg for induction and 0.37mg/kg/min constant rate infusion for maintenance. Rocuronium bromide (0.4mg/kg IV) was used as a peripheral muscle relaxant in order to prevent muscle artifacts. EEGs were recorded digitally using five subdermal needle electrodes. Photic stimulation and hyperventilation were performed to evaluate two activation techniques commonly used in human EEG recording methods. Monopolar and bipolar montages were analyzed visually and quantitatively. The use of rocuronium produced muscle artifact-free EEG recordings during the given recording procedure which indicates that rocuronium is a valuable adjunct to anesthesia during EEG recording. Photic stimulation and hyperventilation did not provoke paroxysmal discharges in the EEG of healthy dogs. Analysis of quantitative EEG data showed that background activity did not differ significantly between periods with and without stimulation. This data are important basic values and will further help to compare the effects of photic stimulation and hyperventilation of healthy dogs and those suffering from epilepsy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The influence of a modified open lung concept (mOLC) on pulmonary and cardiovascular function during total intravenous anaesthesia (TIVA) in horses was evaluated. Forty-two warmblood horses (American Society of Anesthesiologists class 1 to 2), scheduled for elective surgery (mean [sd] weight 526 [65] kg, age 6.4 [5.4] years) were randomly divided into three groups: ventilation with mOLC, intermittent positive-pressure ventilation (IPPV), and spontaneous breathing. Premedication (0.8 mg/kg xylazine), induction (2.2 mg/kg ketamine and 0.05 mg/kg diazepam) and maintenance of anaesthesia with TIVA (1.4 mg/kg/hour xylazine, 5.6 mg/kg/hour ketamine and 131.1 mg/kg/hour guaifenesin), with inhalation of 35 per cent oxygen in air, were identical in all horses. Heart rate, respiratory rate, mean arterial blood pressure (MAP), pH, and arterial partial pressure of oxygen (p(a)O(2)) and carbon dioxide (p(a)CO(2)) were evaluated. Data were collected every 10 minutes from 20 to 90 minutes anaesthesia time. Factorial analysis of variance and Tukey's post hoc test were used for statistical analysis (a=5 per cent). Horses in the mOLC-ventilated group had an overall significantly higher p(a)O(2) (16.9 [1.0] v 11.7 [1.34] v 10.5 [0.57] kPa) and lower MAP (93.1 [5.47] v 107.1 [6.99] v 101.2 [5.45] mmHg) than the IPPV and spontaneously breathing groups, respectively.

The objective of this study was to investigate the cardiopulmonary effects of dorsal recumbency and high-volume caudal epidural anaesthesia induced by xylazine or lidocaine in calves. Twenty-eight German Holstein-Friesian calves (57.7 ± 5.8 kg bodyweight) were randomly allocated to four equal (n=7) groups for one of the following treatments, each injected into the caudal epidural space: (1) no treatment (control); (2) sterile saline (0.4 mL/kg); (3) lidocaine (2%), or (4) xylazine (0.1mg/kg), with the latter two treatments diluted with sterile saline to a final volume of 0.4 mL/kg. Cardiac output was measured by thermodilution and cardiopulmonary function parameters were determined at preset time intervals over an observation period of 335 min. After baseline measurements in the standing animals, the calves received the epidural injection and were positioned in dorsal recumbency for 95 min. In the control group, dorsal recumbency caused a significant (P < 0.05) decrease in cardiac index (CI) (baseline 210 ± 12 mL/kg/min, minimum value 174 ± 11 mL/kg/min), without significant change in blood-gas values. Calves treated with lidocaine or saline did not differ from the control group in any of the parameters measured. The epidural injection of xylazine caused a more pronounced decrease in CI (baseline 209 ± 12 mL/kg/min, minimum value 127 ± 11 mL/kg/min), compared to the control group. At the same time, the heart rate was significantly (P < 0.05) decreased (baseline 113 ± 7 beats per min, minimum value 86 ± 4 beats per min). Furthermore, a significant (P < 0.05) increase in the oxygen extraction ratio was observed in the xylazine group (baseline 39 ± 7%, maximum value 47 ± 7%). In all groups, cardiorespiratory parameters remained within physiological limits. Changes in cardiopulmonary function induced by dorsal recumbency and high-volume caudal epidural anaesthesia with lidocaine or xylazine were well tolerated in healthy calves., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Air pressure is commonly used to drive a mechanical stimulus for nociceptive threshold testing. This may be bulky, noisy, non-linear and suffer from friction, hence development of a better system is described. A novel, light (14 g) rolling diaphragm actuator was constructed, which supplied 20 N force via a constant actuation area irrespective of the pressure and position in the stroke. Three round-ended pins, 2.5 mm diameter, mounted in a triangle on the piston, provided the stimulus. Pressure was increased manually using a syringe with the rate of rise of force controlled at 0.8 N/s by warning lights. The pressure/force relationship was calibrated using a static force transducer and mercury column. Data were collected with the actuator attached to the antero-medial radius of 12 cats and four dogs. Mechanical threshold was recorded when the animal withdrew the limb and/or turned towards the actuator. Safety cut-off was 20 N. The pressure/force relationship was linear and independent of the start point in the actuator stroke. Baseline feline thresholds were 10.0 +/- 2.5 N (mean +/- SD), which increased significantly 30 min after butorphanol administration. Baseline canine thresholds were 5.5 +/- 1.4 N and increased significantly between 15 and 45 min after administration of fentanyl or butorphanol. The system overcame the problems of earlier devices and detected an opioid-induced increase in threshold. It has considerable advantages over previous systems for research in analgesia.

Alpha(2) agonist-induced pulmonary oedema in sheep might be related to alterations in pulmonary haemodynamics and/or activation of inflammatory processes. In seven sevoflurane-anaesthetized sheep pulmonary haemodynamics, arterial oxygen tensions, nitric oxide and prostaglandin E(2) concentrations were determined before and after intravenous dexmedetomidine (2microg kg(-1)). In a second trial, lung tissue was sampled for histopathology and quantitative real-time PCR for IL-1beta and iNOS mRNA in a control sheep and 2, 10 and 30min after dexmedetomidine. Computer tomography of the lung under sevoflurane anaesthesia before and after dexmedetomidine was performed. Two minutes after dexmedetomidine mean pulmonary artery pressure, pulmonary arterial occlusion pressure and estimated capillary pressurewere significantly increased to 34.5mmHg, 22.2mmHg and 27.1mmHg, respectively. On computer tomography, lung density increased immediately after dexmedetomidine, with maximal density occurring between 9 and 12min. Histopathology was consistent with vascular congestion followed by protein and erythrocyte extravasation into alveoli. Increased iNOS mRNA levels were detected in sevoflurane anaesthetized animals only. An IL-1beta signal occurred after morphological changes had occurred in lung tissue. These findings support hydrostatic stress as the underlying cause of alpha(2) agonist-induced pulmonary oedema in sheep.

In sheep, alpha(2)-agonists can induce severe hypoxaemia. In goats, reports on changes in oxygenation are inconsistent. The aim of this study was to compare the cardiopulmonary effects of dexmedetomidine in six goats and four sheep anaesthetised with sevoflurane and maintained at approximately 1 minimal alveolar concentration. The animals were ventilated mechanically and held in an upright position to minimise the influence of positioning on pulmonary function. After baseline cardiopulmonary measures, 2 microg/kg dexmedetomidine was injected intravenously over one minute, and measurements were made for 120 minutes. In both species, respiratory resistance, alveolar dead space and shunt fraction increased and thoracic compliance decreased significantly; arterial, pulmonary arterial, pulmonary capillary wedge and central venous pressures increased and heart rate and cardiac output decreased significantly. Arterial oxygen tension decreased significantly, with no significant difference between the goats and sheep. Wide interindividual differences were observed in both the goats (mean [sd] 144 [149.1] mmHg, range 54.8 to 443.7 mmHg) and sheep (mean [sd] 129.8 [132.1] mmHg, range 33.7 to 352.8 mmHg), but the cardiovascular and respiratory changes were similar in the two species.

Objective: To review the use and adverse effects of alpha(2)-agonists in sheep., Study Design: Literature review., Material and Methods: 'Pubmed' of the United States National Library of Medicine and 'Veterinary Science' of CAB International were searched for references relating sheep to alpha(2)-agonists. The bibliographies of retrieved articles were further scrutinized for pertinent references, and relevant articles were selected manually., Results: Reports on the use of clonidine, xylazine, detomidine, romifidine, medetomidine and dexmedetomidine, MPV-2426 and ST-91 in sheep were found in the literature. Most of the studies described xylazine followed by medetomidine and clonidine. The literature on detomidine and romifidine in sheep was sparse. Reports included pharmacokinetic studies, evaluation of sedative, analgesic, and anaesthetic techniques with or without cardiovascular effects, and experimental investigations of adverse effects (mainly hypoxaemia) including the mechanisms of pulmonary oedema and impaired oxygenation after alpha(2)-agonist administration., Conclusions: A(2)-agonists are potent and effective analgesics in sheep. In combination with ketamine, they are frequently used for the induction and maintenance of anaesthesia, in this case analgesia is satisfactory. The degree of hypoxaemia which occurs with all commercially available alpha(2)-agonists is highly variable and depends on individual or breed-related factors; the most severe reactions occur after intravenous (IV) injection and during general anaesthesia. Clinical relevance Subclinical respiratory disease is common in sheep. Rapid IV injection of alpha(2)-agonists without supplementary oxygen should be avoided whenever hypoxaemia may be critical.

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.