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1.
Reasons for performing study: Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objectives: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Hypothesis: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Methods: Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 μg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography‐mass spectrometry. Data were summarised as mean ± s.d. for subsequent analysis of variance for repeated measures. Results: Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 ± 71.6 ng/ml vs. 6.9 ± 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 ± 23 cm from the ground 10 min following i.v. detomidine and to 64 ± 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Conclusions: Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Potential relevance: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.  相似文献   

2.
Intraoperative bradycardia is not an uncommon complication in anaesthetised horses and it has been recommended that severe bradycardia (defined as heart rate (HR) <25 beats/min) during general anaesthesia, when associated with hypotension (mean arterial pressure (MAP) <70 mmHg) and other signs of inadequate tissue perfusion, should be treated with anticholinergics. Muscarinic antagonists, such as atropine and glycopyrrolate, cause positive chronotropism and dromotropism (improved atrioventricular conduction) by competitively blocking the effects of acetylcholine at muscarinic receptors in the heart. However, in horses, prolonged intestinal hypomotility and colic have been associated with the use of atropine and glycopyrrolate which has led to the investigation of the use of hyoscine N-butylbromide (hyoscine NBB) to treat alpha 2 agonist-induced bradycardia in horses. This report describes the successful use of hyoscine NBB to treat symptomatic intraoperative bradycardia in three isoflurane-anaesthetised horses.  相似文献   

3.
Reasons for performing study: Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objectives: To describe the pharmacokinetics of detomidine and its metabolites, 3‐hydroxy‐detomidine (OH‐detomidine) and detomidine 3‐carboxylic acid (COOH‐detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 μg/kg bwt and 4 a single dose i.m. 30 üg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH‐detomidine and COOH‐detomidine were measured at predetermined time points using liquid chromatography‐mass spectrometry. Results: Following i.v. administration, detomidine was distributed rapidly and eliminated with a half‐life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10–18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215–687 ml/kg bwt, respectively. OH‐detomidine was detected sooner than COOH‐detomidine; however, COOH‐detomidine had a much greater area under the curve. Conclusions and potential relevance: These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.  相似文献   

4.
REASONS FOR PERFORMING STUDY: High-dose dobutamine stress echocardiography has been shown to be cardiotoxic and arrhythmogenic in horses. However, the test may have benefit in practice as a pharmacological challenge of exercise without the treadmill being required. OBJECTIVES: To investigate the effect of low-dose dobutamine on cardiac performance in ponies previously treated with atropine, in order to develop a pharmacological protocol that allows examination of the equine heart under stimulation. METHODS: In 13 healthy Shetland ponies, heart rate (HR), stroke index (SI) and cardiac index (CI) were calculated from pulsed-wave Doppler ultrasound measurements performed at rest and during incremental steps of dobutamine infusion. Group 1 (n = 7) received dobutamine infusion at 2 microg/kg bwt/min for 5 mins followed by incremental rates of 5 microg/kg bwt/min every 5 mins, from 5 to 40 microg/kg bwt/min. Group 2 (n = 6) received dobutamine infusion in incremental rates of 1 microg/kg bwt/min, every 5 mins, from 2 microg/kg bwt/min to 5 microg/kg bwt/min, after premedication with 2 injections of 25 microg/kg bwt of atropine 5 mins apart. RESULTS: The increase in CI during the pharmacological challenge was higher in Group 2 and reached about 2.5 times the resting value. This increase in CI was mediated by a significant increase in HR in both groups, while SI significantly decreased in Group 1 and did not change significantly in Group 2. Ponies of Group 1, but not those of Group 2, showed excessive restlessness and cardiac arrhythmias during the pharmacological challenge and a high intragroup variability in cardiac response. CONCLUSIONS: The results of this study suggest that a low dose of dobutamine in ponies previously given atropine could be a helpful pharmacological protocol to perform stress echocardiography in equids. POTENTIAL RELEVANCE: Further studies should evaluate left ventricular wall motion in horses undergoing low-dose dobutamine protocol after pretreatment with atropine.  相似文献   

5.
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   

6.
Reasons for performing study: No studies have been reported on the effects of enoximone in anaesthetised colic horses. Objective: To examine whether enoximone improves cardiovascular function and reduces dobutamine requirement in anaesthetised colic horses. Methods: Forty‐eight mature colic horses were enrolled in this prospective, randomised clinical trial. After sedation (xylazine 0.7 mg/kg bwt) and induction (midazolam 0.06 mg/kg bwt, ketamine 2.2 mg/kg bwt), anaesthesia was maintained with isoflurane in oxygen and a lidocaine constant rate infusion (1.5 mg/kg bwt, 2 mg/kg/h). Horses were ventilated (PaCO2<8.00 kPa). If hypotension occurred, dobutamine and/or colloids were administered. Ten minutes after skin incision, horses randomly received an i.v. bolus of enoximone (0.5 mg/kg bwt) or saline. Monitoring included respiratory and arterial blood gases, heart rate (HR), arterial pressure and cardiac index (CI). Systemic vascular resistance (SVR), stroke index (SI) and oxygen delivery index (DO2I) were calculated. For each variable, changes between baseline and T10 within each treatment group and/or colic type (small intestines, large intestines or mixed) were analysed and compared between treatments in a fixed effects model. Differences between treatments until T30 were investigated using a mixed model (α= 0.05). Results: Ten minutes after enoximone treatment, CI (P = 0.0010), HR (P = 0.0033) and DO2I (P = 0.0007) were higher and SVR lower (P = 0.0043) than at baseline. The changes in CI, HR and SVR were significantly different from those after saline treatment. During the first 30 min after enoximone treatment, DO2I (P = 0.0224) and HR (P = 0.0003) were higher than after saline administration. Because the difference in HR between treatments was much clearer in large intestine colic cases, an interaction was detected between treatment and colic type in both analyses (P = 0.0076 and 0.0038, respectively). Conclusions: Enoximone produced significant, but short lasting, cardiovascular effects in colic horses. Potential relevance: Enoximone's cardiovascular effects in colic horses were of shorter duration than in healthy ponies.  相似文献   

7.
OBJECTIVE: To determine heart rate (HR) and heart rate variability (HRV) after IV administration of 3 doses of atropine to clinically normal, large-breed adult dogs. ANIMALS: 6 mixed-breed dogs, weighing between 23 and 50 kg. PROCEDURE: Continuous ECG were recorded prior to and following IV administration of saline (0.9% NaCl) solution and 0.02, 0.04, and 0.06 mg of atropine/kg of body weight. Heart rate and HRV within sympathetic and parasympathetic domains were determined, using customized software, and responses to treatments were compared. Each dog received all treatments with > or = 2 days between treatments. RESULTS: HR increased and HRV within the parasympathetic domain decreased after all atropine treatments, compared with pretreatment values. Heart rate was significantly higher after administration of 0.06 mg of atropine/kg than after 0.02 mg/kg but was not different from HR after administration of 0.04 mg/kg. Five of 6 dogs given the 0.04 or 0.06 mg/kg dose attained HR > 135 beats/min, but only 1 of 6 dogs given the 0.02 mg/kg dose attained a HR > 135 beats/min. Heart rate variability within the parasympathetic domain decreased significantly from pretreatment values after all atropine treatments. Atropine doses of 0.04 and 0.06 mg/kg induced significantly lower HRV than did the 0.02 mg/kg dose, but HRV after the higher doses were not different from each other. HRV within the sympathetic domain after any treatment did not change from pretreatment values. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of 0.04 or 0.06 mg of atropine/kg increased HR and induced complete parasympathetic blockade in clinically normal, large-breed adult dogs.  相似文献   

8.
Nine horses were each anaesthetised for 40 min using SufentaniVhalothane. No surgery was performed. After premedication (detomidine 5 pgkg bwt iv) induction of anaesthesia was achieved by a combination of guaiphenesinlthiopentone. Anaesthesia was maintained by inhalation of halothane (0.8%) in oxygen. Six horses (Group 1) received 1 pgkg bwt sufentanil followed by a second injection (1 pg/kg bwt) after 20 min. Three horses (Group 2) received 2 pg/kg bwt sufentanil also followed by a second injection (2 pg/kg bwt) after 20 min. Each sufentanil injection produced a slight decrease in mean arterial blood pressure with a gradual return to the initial pressure. Bradycardia was also observed. Sufentanil injection induced apnoea needing artificial ventilation. Arterial blood was sampled for analysis during the anaesthetic procedure. At the end of anaesthesia, 1 h and 24 h after rising, venous blood was sampled to determine concentrations of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and creatine phosphokinase (CPK). Values obtained were compared with values in blood taken before premedication. Plasma glucose and lactate concentrations just before sufentanil administration, at the end of anaesthesia and 1 h after rising were compared to control values. Plasma glucose concentration increased significantly during anaesthesia but returned to normal values 1 h after rising. All other parameters stayed within physiological ranges. In both groups spontaneous respiration returned 20–25 min after the second sufentanil injection. Recovery was uneventful.  相似文献   

9.
The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine. KEY WORDS: cardiovascular effect, detomidine, equine, medetomidine, xylazine.  相似文献   

10.
REASONS FOR PERFORMING STUDY: It has been reported that i.v. flecainide has a high efficacy for the treatment of experimentally-induced acute atrial fibrillation (AF) in horses and that its use is associated with minimal toxic side effects. OBJECTIVES: The objectives were to study the efficacy of i.v. flecainide as a treatment for atrial fibrillation in horses with naturally-occurring AF. METHODS: Ten horses with naturally-occurring AF were treated with 2 mg/kg bwt flecainide i.v. at a rate of 0.2 mg/kg bwt/min. In 3 horses, the infusion was continued at 0.05-0.10 mg/kg bwt/min until a total dose of 3.0 mg/kg bwt had been administered. Heart rate, QRS duration and average interval between fibrillation waves were measured before, during and following flecainide infusion. If conversion to normal sinus rhythm was not achieved, horses were treated with quinidine sulphate per os at a dose of 22 mg/kg bwt given every 2 h. RESULTS: None of the horses with chronic AF (n = 9) converted to sinus rhythm with flecainide i.v. The only horse treated successfully had acute AF of 12 days' duration. The QRS duration and fibrillation cycle length increased significantly (P = 0.006 and 0.002, respectively) during and following flecainide infusion. Heart rate did not increase significantly over time however, 3 horses developed heart rates in excess of 100 beats/min. Two horses developed a potentially dangerous ventricular dysrhythmia during the first 15 mins of treatment. Quinidine sulphate given per os restored sinus rhythm in 8 out of 9 horses, with minimal adverse effects. CONCLUSIONS: Although flecainide might be efficacious in cases of acute AF, it was not possible to restore sinus rhythm in horses with naturally-occurring chronic AF at the dosages used in this study. In 2 horses, 2.0 mg/kg bwt flecainide was associated with potentially dangerous dysrhythmias. POTENTIAL CLINICAL RELEVANCE: Intravenous administration of 2 mg/kg bwt flecainide is unlikely to convert chronic AF in horses and could induce dangerous dysrhythmias.  相似文献   

11.
The effects of hyoscine-N-butylbromide (hyoscine) and propantheline-bromide (propantheline) on heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) contractions in the normal horse were determined. Five adult horses had ECG recordings for 180min after treatment with propantheline (100mg), hyoscine (120mg) or saline. Both propantheline and hyoscine reduced GIT sounds, with propantheline having a longer duration of effect (?120min). Both drugs elevated HR relative to the control baseline period (P<0.05), with the effects of propantheline again being of longer duration. HRV analysis indicated that propantheline suppressed Total Power (P<0.05), and both the high frequency (HF) and low frequency (LF) components of the power spectral analysis for up to 60-90min post treatment. Hyoscine had no effect on HRV Total Power but reduced the HF component for 30min after drug injection. Time domain variables correlated with Total Power and HF data (P<0.01). The marked effect of these compounds on parasympathetic control of cardiac and GIT function in normal horses should be taken into consideration when evaluating a clinical response to these agents.  相似文献   

12.
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   

13.
OBJECTIVE: To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M2) antagonist, methoctramine, in anesthetized horses. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 microg/kg, i.v.) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 microg/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period. RESULTS: Methoctramine was given at a total cumulative dose of 30 microg/kg to 4 horses, whereas 2 horses received 10 microg/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M2 antagonists may represent a safe alternative for treatment of horses with intraoperative bradycardia.  相似文献   

14.
OBJECTIVE: To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. ANIMALS: 100 client-owned horses. PROCEDURE: After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. RESULTS: Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.  相似文献   

15.
REASON FOR PERFORMING STUDY: Endoscopy of the upper airways of horses is used as a diagnostic tool and at purchase examinations. On some occasions it is necessary to use sedation during the procedure and it is often speculated that the result of the examination might be influenced due to the muscle-relaxing properties of the most commonly used sedatives. OBJECTIVES: To evaluate the effect of detomidine (0.01 mg/kg bwt) and acepromazine (0.05 mg/kg bwt) on the appearance of symmetry of rima glottidis, ability to abduct maximally the arytenoid cartilages and the effect on recurrent laryngeal neuropathy (RLN) grade. METHODS: Forty-two apparently normal horses underwent endoscopic examination of the upper airways on 3 different occasions, under the influence of 3 different treatments: no sedation (control), sedation with detomidine and sedation with acepromazine. All examinations were performed with a minimum of one week apart. The study was performed as an observer-blind cross-over study. RESULTS: Sedation with detomidine had a significant effect on the RLN grading (OR = 2.91) and ability maximally to abduct the left arytenoid cartilages (OR = 2.91). Sedation with acepromazine resulted in OR = 2.43 for the RLN grading and OR = 2.22 for the ability to abduct maximally. The ability to abduct maximally the right arytenoid cartilage was not altered. CONCLUSIONS: Sedating apparently healthy horses with detomidine or acepromazine significantly impairs these horses' ability to abduct fully the left but not the right arytenoid cartilage. This resulted in different diagnosis with respect to RLN when comparing sedation to no sedation. POTENTIAL RELEVANCE: Since the ability to abduct the right arytenoid cartilage fully is not altered by sedation, it is speculated that horses changing from normal to abnormal laryngeal function when sedated, might be horses in an early stage of the disease. To confirm or reject these speculations, further studies are needed. Until then sedation during endoscopy should be used with care.  相似文献   

16.
Reasons for performing study: To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. Objectives: To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. Methods: Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3–10 years, 500–560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within‐subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at P<0.05. Results: Mean (± s.d.) durations of thermal antinociception following treatment administration were: Glu 0.5 (1.1), But 2.9 (2.0), Bup5 7.4 (2.3), Bup7.5 7.8 (2.7) and Bup10 9.4 (1.1) h. B5, B7.5 and B10 were significantly different from Glu and But. No serious adverse effects occurred, although determination of mechanical thresholds was confounded by locomotor stimulation. Conclusions: Administration of acepromazine and all doses of buprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. Potential relevance: This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile.  相似文献   

17.
Reasons for performing study: No studies have determined the pharmacokinetics of low‐dose amikacin in the mature horse. Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n = 6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n = 6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean ± s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144 ± 21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8 ± 7.44 µg/ml, area under the curve 139 ± 34.0 µg*h/ml, elimination half‐life 1.34 ± 0.408 h, total body clearance 1.25 ± 0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81 ± 0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (Cmax) 19.7 ± 7.14 µg/ml and 21.4 ± 4.39 µg/ml and time to maximum concentration 65 ± 12.2 min and 115 ± 12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7 ± 5.34 µg/ml and after 24 h the mean concentration was 3.31 ± 1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean Cmax : MIC ratio was 16.9 ± 1.80 in plasma, 4.95 ± 1.78 in synovial fluid, 5.36 ± 1.10 in peritoneal fluid and 3.18 ± 1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram‐negative bacteria. Potential relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.  相似文献   

18.
OBJECTIVE: To evaluate propofol for induction and maintenance of anesthesia, after detomidine premedication, in horses undergoing abdominal surgery for creation of an experimental intestinal adhesion model. STUDY DESIGN: Prospective study. ANIMALS: Twelve horses (424 +/- 81 kg) from 1 to 20 years of age (5 females, 7 males). METHODS: Horses were premedicated with detomidine (0.015 mg/kg i.v.) 20 to 25 minutes before induction, and a propofol bolus (2 mg/kg i.v.) was administered for induction. Propofol infusion (0.2 mg/kg/min i.v.) was used to maintain anesthesia. The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by muscle relaxation, occular signs, response to surgery, and cardiopulmonary responses. Oxygen (15 L/min) was insufflated through an endotracheal tube as necessary to maintain the SpO2 greater than 90%. Systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures, heart rate (HR), electrocardiogram (ECG), respiratory rate (RR), SpO2 (via pulse oximetry), and nasal temperature were recorded at 15 minute intervals, before premedication and after induction of anesthesia. Arterial blood gas samples were collected at the same times. Objective data are reported as mean (+/-SD); subjective data are reported as medians (range). RESULTS: Propofol (2.0 mg/kg i.v.) induced anesthesia (mean bolus time, 85 sec) within 24 sec (+/-22 sec) after the bolus was completed. Induction was good in 10 horses; 2 horses showed signs of excitement and these two inductions were not smooth. Propofol infusion (0.18 mg/kg/min +/- 0.04) was used to maintain anesthesia for 61 +/- 19 minutes with the horses in dorsal recumbency. Mean SAP, DAP, and MAP increased significantly over time from 131 to 148, 89 to 101, and 105 to 121 mm Hg, respectively. Mean HR varied over time from 43 to 45 beats/min, whereas mean RR increased significantly over anesthesia time from 4 to 6 breaths/min. Mean arterial pH decreased from a baseline of 7.41 +/- 0.07 to 7.30 +/- 0.05 at 15 minutes of anesthesia, then increased towards baseline values. Mean PaCO2 values increased during anesthesia, ranging from 47 to 61 mm Hg whereas PaO2 values decreased from baseline (97 +/- 20 mm Hg), ranging from 42 to 57 mm Hg. Muscle relaxation was good and no horses moved during surgery: Recovery was good in 9 horses and acceptable in 3; mean recovery time was 67 +/- 29 minutes with 2.4 +/- 2.4 attempts necessary for the horses to stand. CONCLUSIONS: Detomidine-propofol anesthesia in horses in dorsal recumbency was associated with little cardiovascular depression, but hypoxemia and respiratory depression occurred and some excitement was seen on induction. CLINICAL RELEVANCE: Detomidine-propofol anesthesia is not recommended for surgical procedures in horses if dorsal recumbency is necessary and supplemental oxygen is not available (eg, field anesthesia).  相似文献   

19.
Combined use of detomidine with opiates in the horse   总被引：2，自引：0，他引：2  
The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Side effects seen were increased ataxia (greatest following methadone and butorphanol) and excitement (usually muzzle tremors and muscle twitching). Following pethidine, generalised excitement was sometimes seen. Marked cardiovascular changes occurred in the first few minutes after morphine or pethidine injection, but within 5 mins cardiovascular changes were minimal. Following morphine or pethidine there was a significant increase in arterial carbon dioxide tension. Fourteen clinical cases were successfully sedated using detomidine/butorphanol combinations.  相似文献   

20.
The reversal of detomidine-induced sedation with iv atipamezole was studied in 6 horses. All horses were injected iv with 10 μg and 20 μg/kg bwt detomidine and 15 min later this was followed by 6-, 8- and 10-fold doses of iv atipamezole. Atipamezole caused a quick arousal in all horses with minor side effects. Bradycardia, rhythm disturbances and head ptosis caused by detomidine were not abolished completely at the end of the 15 min observation period, even with the highest atipamezole doses. All horses remained slightly sedated but without ataxia. There were no significant differences in head height, heart rate and sedation score between the different doses of atipamezole for either dose of detomidine. According to the degree of sedation, doses of 100 μg to 160 μg/kg bwt atipamezole are adequate to antagonise detomidine-induced sedation in the horse.  相似文献   

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