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1.
ObjectiveTo evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 63 healthy horses undergoing elective surgery during general anaesthesia.MethodsHorses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg–1), maintenance (40 μg kg–1 hour–1) and before recovery (20 μg kg–1). In group D2.5, horses were given detomidine IV for premedication (15 μg kg–1), maintenance (5 μg kg–1 hour–1) and before recovery (2.5 μg kg–1). In group D5, horses were given the same doses of detomidine IV for premedication and maintenance but 5 μg kg–1 prior to recovery. Premedication was combined with morphine IV (0.1 mg kg–1) in all groups. Cardiovascular and blood gas variables, expired fraction of isoflurane (Fe′Iso), dobutamine or ketamine requirements, recovery times, recovery events scores (from sternal to standing position) and visual analogue scale (VAS) were compared between groups using either anova followed by Tukey, Kruskal-Wallis followed by Bonferroni or chi-square tests, as appropriate (p < 0.05).ResultsNo significant differences were observed between groups for Fe′Iso, dobutamine or ketamine requirements and recovery times. Cardiovascular and blood gas measurements remained within physiological ranges for all groups. Group D5 horses had significantly worse scores for balance and coordination (p = 0.002), overall impression (p = 0.021) and final score (p = 0.008) than group R horses and significantly worse mean scores for VAS than the other groups (p = 0.002).Conclusions and clinical relevanceDetomidine or romifidine constant rate infusion provided similar conditions for maintenance of anaesthesia. Higher doses of detomidine at the end of anaesthesia might decrease the recovery quality.  相似文献   

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ObjectiveTo describe selected pharmacodynamic effects of detomidine and yohimbine when administered alone and in sequence.Study designRandomized crossover design.AnimalsNine healthy adult horses aged 9 ± 4 years and weighing 561 ± 56 kg.MethodsThree dose regimens were employed in the current study. 1) 0.03 mg kg?1 detomidine IV, 2) 0.2 mg kg?1 yohimbine IV and 3) 0.03 mg kg?1 detomidine IV followed 15 minutes later by 0.2 mg kg?1 yohimbine IV. Each horse received all three treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume and plasma proteins were monitored.ResultsYohimbine rapidly reversed the sedative effects of detomidine in the horse. Additionally, yohimbine effectively returned heart rate and the percent of atrio-ventricular conduction disturbances to pre-detomidine values when administered 15 minutes post-detomidine administration. Plasma glucose was significantly increased following detomidine administration. The detomidine induced hyperglycemia was effectively reduced by yohimbine administration. Effects on packed cell volume and plasma proteins were variable.Conclusions and clinical relevanceIntravenous administration of yohimbine effectively reversed detomidine induced sedation, bradycardia, atrio-ventricular heart block and hyperglycemia.  相似文献   

4.
ObjectiveTo investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.Study designExperimental, crossover study with a 14 day wash-out period.AnimalsSeven healthy horses.MethodsThe horses received either detomidine (20 μg kg−1 IV) and butorphanol (20 μg kg−1 IV) alone (DET) or with MK-467 (200 μg kg−1 IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg−1) and midazolam (0.06 mg kg−1) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (PaO2/FiO2) and tissue oxygen delivery (DO2) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.ResultsThe induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and PaO2/FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.Conclusions and clinical relevanceMK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.  相似文献   

5.
ObjectiveTo investigate plasma drug concentrations and the effect of MK-467 (L-659′066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.Study designExperimental randomized blinded crossover study.AnimalsSix healthy horses.MethodsDetomidine (10 μg kg?1 IV) was administered alone (DET) and in combination with MK-467 (250 μg kg?1 IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed) and pharmacokinetic parameters. Significance was set at p < 0.05.ResultsA significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.Conclusions and clinical relevanceMK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.  相似文献   

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ObjectiveTo describe the pharmacokinetics of detomidine and yohimbine when administered in combination.Study designRandomized crossover design.AnimalsNine healthy adult horses aged 9 ± 4 years and weighing of 561 ± 56 kg.MethodsThree dose regimens were employed in the current study. 1) 0.03 mg kg?1 detomidine IV (D), 2) 0.2 mg kg?1 yohimbine IV (Y) and 3) 0.03 mg kg?1 detomidine IV followed 15 minutes later by 0.2 mg kg?1 yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1 week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis.ResultsThe maximum measured detomidine concentrations were 76.0 and 129.9 ng mL?1 for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9 ng mL?1) to DY (289.8 ng mL?1). Both the Cl and Vd for yohimbine were significantly less (6.8 mL minute?1 kg?1 (Cl) and 1.7 L kg?1 (Vd)) for the DY as compared to the Y treatments (13.9 mL minute?1 kg?1 (Cl) and 2.7 L kg?1 (Vd)). Plasma concentrations were below the limit of quantitation (0.05 and 0.5 ng mL?1) by 18 hours for both detomidine and yohimbine.Conclusion and clinical relevanceThe Cl and Vd of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted.  相似文献   

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ObjectiveTo describe the effects of alpha2-adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse.Study designRandomized crossover design.AnimalsNine healthy adult horses with an average age of 7.6 ± 6.5 years.MethodsFour treatment groups were studied: 1) 0.04 mg kg?1 detomidine SL; 2) 0.04 mg kg?1 detomidine SL followed 1 hour later by 0.075 mg kg?1 yohimbine intravenously (IV); 3) 0.04 mg kg?1 detomidine SL followed 1 hour later by 4 mg kg?1 tolazoline IV; and 4) 0.04 mg kg?1 detomidine SL followed 1 hour later by 0.12 mg kg?1 atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored.ResultsChin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume.Conclusions and clinical relevanceAt the doses administered in this study, the alpha2-adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.  相似文献   

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ObjectiveTo assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses.Study designRandomized, blinded, three-way crossover prospective design.AnimalsA total of eight healthy adult horses weighing 470–575 kg.MethodsHorses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine–zolazepam (1.2 mg kg−1), ketamine (1 mg kg−1) and detomidine (0.04 mg kg−1) (treatment TKD); ketamine (3 mg kg−1) and detomidine (0.04 mg kg−1) (treatment KD); and tiletamine–zolazepam (2.4 mg kg−1) and detomidine (0.04 mg kg−1) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings–Mack test. A p value <0.05 was considered statistically significant.ResultsAll horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO2 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality.Conclusions and clinical relevanceIn domestic horses, IM injections of tiletamine–zolazepam–detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine–detomidine and tiletamine–zolazepam–ketamine–detomidine. Recoveries were comparable among protocols.  相似文献   

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ObjectiveTo compare the analgesic efficacy of buprenorphine plus detomidine with that of morphine plus detomidine when administered epidurally in horses undergoing bilateral stifle arthroscopy.Study designProspective, randomized, blinded clinical trial.AnimalsTwelve healthy adult horses participating in an orthopedic research study. Group M (n = 6) received morphine (0.2 mg kg?1) and detomidine (0.15 mg kg?1) epidurally; group B (n = 6) received buprenorphine (0.005 mg kg?1) and detomidine (0.15 mg kg?1) epidurally.MethodsHorses received one of two epidural treatments following induction of general anesthesia for bilateral stifle arthroscopy. Heart rate (HR), mean arterial blood pressure (MAP), end-tidal CO2 (Pe’CO2), and end-tidal isoflurane concentrations (E’Iso%) were recorded every 15 minutes following epidural administration. Post-operative assessment was performed at 1, 2, 3, 6, 9, 12, and 24 hours after standing; variables recorded included HR, respiratory rate (fR), abdominal borborygmi, defecation, and the presence of undesirable side effects. At the same times post-operatively, each horse was videotaped at a walk and subsequently assigned a lameness score (0-4) by three ACVS diplomates blinded to treatment and who followed previously published guidelines. Nonparametric data were analyzed using Wilcoxon’s rank-sum test. Inter- and intra-rater agreement were determined using weighted kappa coefficients. Statistical significance was set at p = 0.05.ResultsNo statistically significant differences were found between groups with respect to intra-operative HR, MAP, E’Iso%, or post-operative HR, gastrointestinal function and cumulative median lameness scores. Post-operative fR in group B [24 (12-30), median (range)] breaths per minute was significantly higher than in group M [18 (15-20)] breaths per minute, p = 0.04.Conclusions and clinical relevanceIn horses undergoing bilateral stifle arthroscopy, these doses of buprenorphine plus detomidine injected epidurally produced analgesia similar in intensity and duration to that of morphine plus detomidine injected epidurally.  相似文献   

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ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg?1) romifidine (ROM, 80 μg kg?1) and a combination of phenylbutazone (4.4 mg kg?1) and romifidine (80 μg kg?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (fR), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.  相似文献   

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ObjectiveTo study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine.Study designRandomised, prospective clinical study.AnimalsTwenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg.MethodsDetomidine at 80 μg kg?1 was administered to ten calves sublingually (GEL) and at 30 μg kg?1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg?1) and local anaesthetic (lidocaine 3 mg kg?1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student’s t-test and linear mixed models as relevant.ResultsThe maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL?1 (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding.Conclusions and clinical relevanceOromucosally administered detomidine is an effective sedative agent for calves prior to disbudding.  相似文献   

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ObjectiveTo compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy.Study designRandomized, controlled, crossover, blinded clinical trial.AnimalsA total of 50 horses with owner consent, excluding stallions.MethodsEach horse was sedated with intravenous acepromazine (0.02 mg kg–1), followed by an α2-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg–1) 5 minutes later. A CRI of the same α2-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg–1; CRI, 6 μg kg–1 hour–1) or medetomidine (bolus dose, 5 μg kg–1; CRI, 3.5 μg kg–1 hour–1). If sedation was inadequate, a quarter of the initial bolus of the α2-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance.ResultsTotal treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions.Conclusions and clinical relevanceMedetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.  相似文献   

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ObjectiveTo evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses.Study designRandomized, crossover experimental study.AnimalsEight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years.MethodsBaseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2oAV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO2) and oxygen (PaO2) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg?1; group HIV), IM hyoscine (0.3 mg kg?1; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg?1) was administered IV and measurements were recorded at various time points for 130 minutes.ResultsMedetomidine induced bradycardia, 2oAV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2oAV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute?1 and 241 ± 37 mmHg versus 65 ± 16 beats minute?1 and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO2 and PaO2 were not significantly changed by administration of medetomidine with or without hyoscine.Conclusion and clinical relevanceHyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.  相似文献   

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ObjectiveTo compare the changes in splenic length and thickness and in packed cell volume (PCV) following detomidine or xylazine administration and subsequent epinephrine infusion. Hypothesis: Spleen relaxation occurs following xylazine or detomidine administration and interferes with subsequent splenic contractile response to epinephrine.Study designRandomized non‐blinded crossover experimental study.Animals6 healthy adult mares.MethodsThe mares received an intravenous (IV) epinephrine infusion (1 μg kg?1minute?1 over 5 minutes) one hour after IV administration of detomidine (0.01 mg kg?1), xylazine (0.5 mg kg?1) or no drug (control), with a withdrawal period of at least 7 days between experiments. The splenic length measured in two different axes, the splenic thickness, and the PCV were measured prior to sedation (T0), 30 minutes later, and at 5‐minute intervals from the start of the epinephrine infusion (T1) until T1 + 40 minutes. Changes from base‐line and between treatments were compared using a two‐way anova for repeated measures. Significance was set at p < 0.05.ResultsSplenic length was significantly increased and PCV was significantly decreased after detomidine administration compared to baseline. Epinephrine infusion resulted in a significant decrease in splenic length and thickness, and a significant increase in PCV, irrespective of prior treatment with detomidine or xylazine.ConclusionsDetomidine administration was followed by a sonographically detectable increase of splenic length. Neither detomidine nor xylazine interfered with the ability of the spleen to contract following subsequent administration of an epinephrine infusion given one hour later.Clinical relevancePrevious sedation with alpha‐2 agonists does not preclude the efficiency of epinephrine as a medical treatment of left dorsal displacement of the large colon, but further investigations are required with other drug doses and different time intervals between administrations.  相似文献   

16.
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.  相似文献   

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ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg?1, romifidine 0.08 mg kg?1, or xylazine, 1 mg kg?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.  相似文献   

19.

Objective

To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects.

Study design

Randomized, placebo-controlled, blinded, crossover.

Animals

A group of eight adult healthy horses aged (mean ± standard deviation) 7 ± 2 years and 372 ± 27 kg.

Methods

A total of six treatments were administered IV: saline (SAL); detomidine (5 μg kg?1; DET); methadone (0.2 mg kg?1; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD) μg kg?1]. Thermal, mechanical and electrical nociceptive thresholds were measured, and sedation, head height above ground (HHAG), cardiopulmonary variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90, 120 and 180 minutes. Normal data were analyzed by mixed-model analysis of variance and non-normal by Kruskal–Wallis (p < 0.05).

Results

Nociceptive thresholds in horses administered methadone with the higher doses of detomidine (MMD, MHD) were increased above baseline to a greater degree and for longer duration (MMD: 15–30 minutes, MHD: 30–60 minutes) than in horses administered low dose with methadone or detomidine alone (MLD, DET: 5–15 minutes). No increases in nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No significant sedation was observed in SAL, MET or MLD. Intestinal motility was reduced for 75 minutes in MHD and for 30 minutes in all other treatments.

Conclusions

Methadone (0.2 mg kg?1) potentiated the antinociception produced by detomidine (5 μg kg?1), with minimal sedative effects.

Clinical relevance

Detomidine (5 μg kg?1) with methadone (0.2 mg kg?1) produced antinociception without the adverse effects of higher doses of detomidine.  相似文献   

20.
ObjectiveTo assess the cardiopulmonary effects of ephedrine and phenylephrine for management of isoflurane‐induced hypotension in horses.Study designProspective randomized clinical study.AnimalsFourteen isoflurane‐anesthetized horses undergoing digital palmar neurectomy.MethodsEphedrine (EPH group; 0.02 mg kg?1 minute?1; n = 7) or phenylephrine (PHE group; 0.002 mg kg?1 minute?1; n = 7) was administered to all horses when mean arterial pressure (MAP) was <60 mmHg. The infusions were ended when the target MAP was achieved, corresponding to a 50% increase over the pre‐infusion MAP (baseline). The horses were instrumented with an arterial catheter to measure blood pressure and allow the collection of blood for pH and blood‐gas analysis and a Swan‐Ganz catheter for measurement of cardiac output using thermodilution. Cardiopulmonary parameters were recorded at baseline and at 5, 30, 60 and 90 minutes after achieving the target MAP.ResultsIn both groups, the MAP and systemic vascular resistance (SVR) increased significantly at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05). The EPH group had a significant increase in cardiac index (CI) and systemic oxygen delivery index at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05) and compared to the PHE group (p < 0.05). The PHE group had significantly higher SVR and no decrease in oxygen extraction compared with the EPH group at 30, 60 and 90 minutes post infusion (p < 0.05). No significant differences in ventilatory parameters were observed between groups after the infusion.ConclusionsEphedrine increased the MAP by increasing CI and SVR. Phenylephrine increased MAP by increasing SVR but cardiac index decreased. Ephedrine resulted in better tissue oxygenation than phenylephrine.Clinical relevanceEphedrine would be preferable to phenylephrine to treat isoflurane‐induced hypotension in horses since it increases blood flow and pressure.  相似文献   

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