首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 15 毫秒
1.
  相似文献   

2.
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   

3.
OBJECTIVE: To determine whether preoperative epidural administration of morphine and detomidine would decrease postoperative lameness after bilateral stifle arthroscopy in horses. STUDY DESIGN: Prospective clinical controlled study. ANIMALS: Eight adult horses that had bilateral arthroscopic procedures, including drilling of cartilage and subchondral bone within the femoropatellar joints. METHODS: Horses were randomly separated into 2 groups. Preoperatively, 4 horses were administered a combination of epidural morphine (0.2 mg/kg) and detomidine (30 microg/kg), and 4 horses were administered an equivalent volume of epidural saline (0.9% NaCl) solution. Postoperative pain was assessed using 6 video recordings made at hourly intervals of each horse at a walk. Assessments began 1 hour after recovery from anesthesia. The recordings were scrambled out of sequence and evaluated by 3 observers, unaware of treatment groups, who scored lameness from 0 to 4. Lameness scores of the 2 groups of horses were compared using a Wilcoxon's rank sum test. Heart and respiratory rates were also measured at each hourly interval and compared between groups using a repeated-measures ANOVA; statistical significance was set at P <.05. RESULTS: Preoperative administration of epidural morphine and detomidine significantly decreased lameness and heart rates after bilateral stifle arthroscopy. The greatest decrease was detected at hours 1 and 2 after recovery from anesthesia. CONCLUSION: We conclude that horses undergoing a painful arthroscopic procedure of the stifle joint benefit from the administration of preoperative epidural morphine and detomidine. CLINICAL RELEVANCE: Preoperative epidural administration of detomidine and morphine may be useful in decreasing postoperative pain after stifle arthroscopy as well as pain associated with other painful disorders involving the stifle joint, such as septic arthritis and trauma.  相似文献   

4.
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   

5.
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   

6.
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   

7.
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   

8.
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   

9.
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   

10.
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   

11.
  相似文献   

12.
ObjectiveTo evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations.Study designNonrandomized, experimental trial.AnimalsFive adult horses, each with a permanent gastric cannula weighing 534 ± 46 kg.MethodsVisceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose–to–ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 μg kg?1) was administered intravenously. Data were analyzed by means of a three–factor anova with fixed factors of treatment and time and random factor of horse. When a significant time × treatment interaction was detected, differences were compared with a simple t–test or Bonferroni t–test. Significance was set at p < 0.05.ResultsDetomidine produced a significant, dose–dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose–dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 μg kg?1 for 15 minutes and for at least 165 minutes with 20 μg kg?1. Duodenal distension threshold was significantly increased at 15 minutes for the 20 μg kg?1 dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes.Conclusions and clinical relevanceDetomidine caused a longer period of visceral anti–nociception as determined by CRD but a shorter period of anti–nociception as determined by DD than has been previously reported. The lack of somatic anti–nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut–off of the testing device.  相似文献   

13.
ObjectiveTo evaluate the effect of epidural morphine on gastrointestinal (GI) motility in horses.Study designRandomly ordered crossover design.AnimalsSix healthy adult horses weighing 585 ± 48 kg (mean ± SD).MethodsHorses were randomly assigned to receive either 0.2 mg kg?1 morphine or an equal volume (0.04 mL kg?1) of saline epidurally (the first inter coccygeal space) with 2 weeks between treatments. The horses were stabled, fed a standardized diet and allowed water ad libitum throughout the duration of the study. Radiopaque spheres were administered by stomach tube. Xylazine 0.2 mg kg?1 intravenously was administered prior to epidural injection. Heart rate, respiratory rate, GI sounds score and behavior score were recorded before drug administration and after epidural injection at 4, 8, 12, 18, 24 hours and every 12 hours thereafter for 6 days. Feces were weighed, radiographed and the number of spheres counted. Data were analyzed using a mixed effect model.ResultsAt no time did horses exhibit signs of colic or show significant differences between treatments regarding heart rate, respiratory rate, GI sounds score, behavior score, or cumulative number of spheres. The concentration of spheres per kg of feces was significantly lower (p < 0.05) for the morphine group at 18 and 24 hours. Using the centroid of the curves (spheres kg?1 plotted versus time) the average transit time after saline epidural was 38 hours and after morphine it was 43 hours. The weight of feces hour?1 was significantly lower (p < 0.05) at only 4 and 8 hours after morphine.Conclusions and clinical relevanceEpidural morphine, at a dose of 0.2 mg kg?1, temporarily reduced GI motility but did not cause ileus or colic in this small group of healthy unfasted horses. Care should be taken when extrapolating these data to situations in which other factors may also affect GI motility.  相似文献   

14.

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   

15.
  相似文献   

16.
Objective To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. Design Retrospective study. Animals Fifty‐one adult horses aged 9.5 ± 6.9 years (range 1–23 years) and weighing 575 ± 290.3 kg. Methods Records of horses presented to our clinic over a 3‐year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. Results Detomidine was administered as an initial bolus loading dose (mean ± SD) of 7.5 ± 1.87 µg kg?1. The initial infusion rate was 0.6 µg kg?1 minute?1, and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. Conclusions Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. Clinical relevance An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics.  相似文献   

17.
ObjectiveTo examine the influence of direct current shock application in anaesthetized horses with atrial fibrillation (AF) and to study the effects of cardioversion to sinus rhythm (SR).Study designProspective clinical study.AnimalsEight horses successfully treated for AF (transvenous electrical cardioversion after amiodarone pre-treatment).MethodsCardioversion catheters and a pacing catheter were placed under sedation [detomidine 10 μg kg?1 intravenously (IV)]. After additional sedation (5–10 μg kg?1 detomidine, 0.1 mg kg?1 methadone IV), anaesthesia was induced with ketamine, 2.2 mg kg?1 and midazolam, 0.06 mg kg?1 (IV) in a sling and maintained with isoflurane in oxygen. Flunixin meglumine, 1.1 mg kg?1, was administered IV. Shocks were delivered as biphasic truncated exponential waves, synchronized with the R-wave of the electrocardiogram. Monitoring included pulse oximetry, electrocardiography, capnography, inhalational anaesthetic agent concentration, arterial blood pressure, LiDCO and PulseCO cardiac index (CI) and arterial blood gases. Values before and after the first unsuccessful shock and before and after cardioversion to SR were compared.ResultsValues before the first shock were comparable to reported values in healthy, isoflurane anaesthetized horses. Reliable CI measurements could not be obtained using the PulseCO technique. Intermittent positive pressure ventilation was required in most horses (bradypnea and/or PaCO2 >8 kPa, 60 mmHg), while dobutamine was administered in two horses (0.3–0.5 μg kg?1 minute?1). After the 1st unsuccessful shock application, systolic arterial pressure (SAP) was decreased (p = 0.025), other recorded values were not influenced (CI measurements not available for this analysis). SR was associated with increases in CI (p = 0.039) and stroke index (p = 0.002) and a decrease in SAP (p = 0.030).Conclusions and clinical relevanceDespite the presence of AF, cardiovascular function was well maintained during anaesthesia and was not affected by shock application. Cardiac index and stroke index increased and SAP decreased after cardioversion.  相似文献   

18.
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.
ObjectivesTo evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine.Study designRandomized, crossover, blinded experiment.AnimalsA group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg).MethodsAlpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 μg kg−1; treatment DET–IV) or detomidine gel (200 μg kg−1; treatment DET–VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography–tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant.ResultsOnset of sedation was faster in treatment DET–IV (1.6 ± 0.2 minutes) than in treatment DET–VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET–IV (8.3 ± 1.3 minutes) than in treatment DET–VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET–IV and DET–VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET–VAG were 39.6 ng mL−1, 19.9 minutes and 20%, respectively.Conclusions and clinical relevanceDetomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.  相似文献   

20.
ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg?1 minute?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号