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1.
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   

2.
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   

3.
Objective To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Study Design Prospective randomized experimental study. Animals Fifteen adult grade mares weighing 328–537 kg. Methods The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg?1): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30, 45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation. Yohimbine (0.1 mg kg?1 IV) was administered after the 90‐minute evaluation. Blood samples were collected from the detomidine‐alone group before treatment and at 15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for detomidine equivalent concentrations by an ELISA. Head droop percentages were compared using a repeated measures analysis of variance. Results Significant mean head droop developed in each treatment group by 30 minutes and persisted until reversal with yohimbine. After yohimbine administration, head positions returned to 87–91% of pre‐treatment levels. There were no significant differences among the oral treatment groups at any time. Mean serum detomidine equivalents increased slowly until 45‐minute post‐administration, but never exceeded 30 ng mL?1. Conclusions Orally administered detomidine results in measurable serum drug concentrations using any of the delivery mediums investigated, and can be expected to produce profound head droop in horses approximately 45 minutes after administration.  相似文献   

4.
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   

5.
ObjectiveTo describe the hypnotic effects of a single bolus dose of propofol in Japanese macaques, and to develop a pharmacokinetic model.Study designProspective experimental trial.AnimalsFour male macaques (5-6 years old, 8.0-11.2 kg).MethodsThe macaque was restrained and 8 mg kg?1 of propofol was administrated intravenously at 6 mg kg?1 minute?1. Behavioural changes without stimuli (first experiment) then responses to external stimuli (the second experiment) were assessed every 2 minutes for 20 minutes. Venous blood samples were collected before and at 1, 5, 15, 30, 60, 120 and 210 minutes after drug administration, and plasma concentrations of propofol were measured (third experiment). Pharmacokinetic modelling was performed using NONMEM VI.ResultsMacaques were recumbent without voluntary movement for a mean 14.0 ± 2.7 SD (range 10.5-16.2) or 10.0 ± 3.4 (7.2-14.5) minutes and recovered to behave as pre-administration by 25.1 ± 3.6 (22.1-30.1) or 22.2 ± 1.5 (21.1-24.3) minutes after the end of propofol administration without or with stimuli, respectively. Respiratory and heart rates were stable throughout the experiments (28-68 breaths minute?1 and 72-144 beats minute?1, respectively). Our final pharmacokinetic model included three compartments and well described the plasma concentration of propofol. The population pharmacokinetic parameters were: V1 = 10.4 L, V2=8.38 L, V3=72.7 L, CL1= 0.442 L minute?1, CL2= 1.14 L minute?1, CL3= 0.313 L minute?1, (the volumes of distribution and the clearances for the central, rapid and slow peripheral compartments, respectively).ConclusionsIntravenous administration of propofol (8 mg kg?1) at 6 mg kg?1 minute?1 to Japanese macaques had a hypnotic effect lasting more than 7 minutes. A three-compartment model described propofol plasma concentrations over more than 3 hours.Clinical relevanceThe developed pharmacokinetic parameters may enable simulations of administration protocols to maintain adequate plasma concentration of propofol.  相似文献   

6.
ObjectiveTo investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs.Study designRandomized, cross-over, experimental trial.AnimalsNine adult dogs (beagle and beagle cross breeds), four males and five females.MethodsMethadone hydrochloride, 0.4 mg kg?1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol.ResultsAfter IV administration, the plasma concentration of methadone at 10 minutes was 82.1 ± 9.2 ng mL?1 (mean ± SD), the terminal half-life was 3.9 ± 1.0 hours, the volume of distribution 9.2 ± 3.3 L kg?1 and plasma clearance 27.9 ± 7.6 mL minute?1 kg?1. After SC administration, time to maximal plasma concentration was 1.26 ± 1.04 hours and maximal plasma concentration of methadone was 23.9 ± 14.4 ng mL?1, the terminal half-life was 10.7 ± 4.3 hours and bioavailability was 79 ± 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic.Conclusion and clinical relevanceWhen methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.  相似文献   

7.
ObjectivesTo evaluate the cardiorespiratory and biochemical effects of ketamine-propofol (KP) or guaifenesin-ketamine-xylazine (GKX) anesthesia in donkeys.Study designProspective crossover trial.AnimalsEight healthy, standard donkeys, aged 10 ± 5 years and weighing 153 ± 23 kg.MethodsDonkeys were premedicated with 1.0 mg kg?1 of xylazine (IV) in both treatments. Eight donkeys were administered ketamine (1.5 mg kg?1) and propofol (0.5 mg kg?1) for induction, and anesthesia was maintained by constant rate infusion (CRI) of ketamine (0.05 mg kg?1 minute?1) and propofol (0.15 mg kg?1 minute?1) in the KP treatment. After 10 days, diazepam (0.05 mg kg?1) and ketamine (2.2 mg kg?1) were administered for induction, and anesthesia was maintained by a CRI (2.0 mL kg?1 hour?1) of ketamine (2.0 mg mL?1), xylazine (0.5 mg mL?1) and guaifenesin (50 mg mL?1) solution. Quality of anesthesia was assessed along with cardiorespiratory and biochemical measurements.ResultsAnesthetic induction took longer in GKX than in KP. The induction was considered good in 7/8 with KP and in 6/8 in GKX. Anesthetic recovery was classified as good in 7/8 animals in both treatments. Xylazine administration decreased heart rate (HR) in both treatments, but in KP the HR increased and was higher than GKX throughout the anesthetic period. Respiratory rate was higher in GKX than in KP. PaO2 decreased significantly in both groups during the anesthetic period. Glucose concentrations [GLU] increased and rectal temperature and PCV decreased in both treatments. Arterial lactate [LAC] increased at recovery compared with all time points in KP. [GLU] and calcium were higher in GKX than in KP at recovery.Conclusion and clinical relevanceThese protocols induced significant hypoxemia but no other cardiorespiratory or metabolic changes. These protocols could be used to maintain anesthesia in donkeys, however, they were not tested in animals undergoing surgery.  相似文献   

8.
ObjectiveTo investigate the cardiorespiratory, nociceptive and endocrine effects of the combination of propofol and remifentanil, in dogs sedated with acepromazine.Study designProspective randomized, blinded, cross-over experimental trial.AnimalsTwelve healthy adult female cross-breed dogs, mean weight 18.4 ± 2.3 kg.MethodsDogs were sedated with intravenous (IV) acepromazine (0.05 mg kg?1) followed by induction of anesthesia with IV propofol (5 mg kg?1). Anesthesia was maintained with IV propofol (0.2 mg kg?1 minute?1) and remifentanil, infused as follows: R1, 0.125 μg kg?1 minute?1; R2, 0.25 μg kg?1 minute?1; and R3, 0.5 μg kg?1 minute?1. The same dogs were administered each dose of remifentanil at 1-week intervals. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (fR), end tidal CO2 (Pe′CO2), arterial hemoglobin O2 saturation, blood gases, and rectal temperature were measured before induction, and 5, 15, 30, 45, 60, 75, 90, and 120 minutes after beginning the infusion. Nociceptive response was investigated by electrical stimulus (50 V, 5 Hz and 10 ms). Blood samples were collected for plasma cortisol measurements. Statistical analysis was performed by anova (p < 0.05).ResultsIn all treatments, HR decreased during anesthesia with increasing doses of remifentanil, and increased significantly immediately after the end of infusion. MAP remained stable during anesthesia (72–98 mmHg). Antinociception was proportional to the remifentanil infusion dose, and was considered satisfactory only with R2 and R3. Plasma cortisol concentration decreased during anesthesia in all treatments. Recovery was smooth and fast in all dogs.Conclusions and clinical relevanceInfusion of 0.25–0.5 μg kg?1 minute?1 remifentanil combined with 0.2 mg kg?1 minute?1 propofol produced little effect on arterial blood pressure and led to a good recovery. The analgesia produced was sufficient to control the nociceptive response applied by electrical stimulation, suggesting that it may be appropriate for performing surgery.  相似文献   

9.
ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg?1 IV). Twenty minutes later they received xylazine (1 mg kg?1 IV), then after 5 minutes, guaiphenesin (35 mg kg?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t1/2), plasma clearance (Clp) and volume of distribution (Vd) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute?1 kg?1 and 1.6 ± 0.4 L kg?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.  相似文献   

10.
ObjectiveTo determine the effect of intravenous ketamine on the minimum alveolar concentration of sevoflurane needed to block autonomic response (MACBAR) to a noxious stimulus in dogs.Study designRandomized, crossover, prospective design.AnimalsEight, healthy, adult male, mixed-breed dogs, weighing 11.2–16.1 kg.MethodsDogs were anesthetized with sevoflurane on two occasions, 1 week apart, and baseline MACBAR (B-MACBAR) was determined on each occasion. MACBAR was defined as the mean of the end-tidal sevoflurane concentrations that prevented and allowed an increase (≥15%) in heart rate or invasive mean arterial pressure in response to a noxious electrical stimulus (50 V, 50 Hz, 10 ms). Dogs then randomly received either a low-dose (LDS) or high-dose series (HDS) of ketamine, and treatment MACBAR (T-MACBAR) was determined. The LDS had an initial loading dose (LD) of 0.5 mg kg?1 and constant rate infusion (CRI) at 6.25 μg kg?1 minute?1, followed, after T-MACBAR determination, by a second LD (1 mg kg?1) and CRI (12.5 μg kg?1 minute?1). The HDS had an initial LD (2 mg kg?1) and CRI (25 μg kg?1 minute?1) followed by a second LD (3 mg kg?1) and CRI (50 μg kg?1 minute?1). Data were analyzed with a mixed-model anova and are presented as LSM ± SEM.ResultsThe B-MACBAR was not significantly different between treatments. Ketamine at 12.5, 25, and 50 μg kg?1 minute?1 decreased sevoflurane MACBAR, and the maximal decrease (22%) occurred at 12.5 μg kg?1 minute?1. The percentage change in MACBAR was not correlated with either the log plasma ketamine or norketamine concentration.Conclusions and clinical relevanceKetamine at clinically relevant doses of 12.5, 25, and 50 μg kg?1 minute?1 decreased sevoflurane MACBAR, although the reduction was neither dose-dependent nor linear.  相似文献   

11.
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   

12.
Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260–320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (30 µg kg?1), butorphanol (20 µg kg?1) and detomidine (10 µg kg?1) preceded induction of anaesthesia with detomidine (10 µg kg?1) and ketamine (2 mg kg?1) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20‐minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL?1), ketamine (4 mg mL?1) and guaiphenesin (100 mg mL?1) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO2 between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO2 was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg?1 hour?1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg?1 hour?1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10‐fold and 2‐fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO2 and PCO2 were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO2 and PCO2 were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine. Ponies took 60 ± 28 minutes to stand and recovery was good. Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while cardiovascular function in mare and fetus was well preserved. This indicates that DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae.  相似文献   

13.
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   

14.
ObjectiveThe objective was to examine the effects of inhibiting cytochrome P450 (CYP) on the pharmacokinetics of oral methadone in dogs.Study designProspective non-randomized experimental trial.AnimalsSix healthy Greyhounds (three male and three female).MethodsThe study was divided into two phases. Oral methadone (mean = 2.1 mg kg?1 PO) was administered as whole tablets in Phase 1. In Phase 2 oral methadone (2.1 mg kg?1 PO) was administered concurrently with ketoconazole (13.0 mg kg?1 PO q 24 hours), chloramphenicol (48.7 mg kg?1 PO q 12 hours), fluoxetine (1.3 mg kg?1 PO q 24 hours), and trimethoprim (6.5 mg kg?1 PO q 24 hours). Blood was obtained for analysis of methadone plasma concentrations by liquid chromatography with mass spectrometry. The maximum plasma concentration (Cmax), time to Cmax (Tmax), and the area under the curve from time 0 to the last measurable time point above the limit of quantification of the analytical assay (AUC0–LAST) were compared statistically.ResultsThe Cmax of methadone was significantly different (p = 0.016) for Phase 1 (5.5 ng mL?1) and Phase 2 (171.9 ng mL?1). The AUC0–LAST was also significantly different (p = 0.004) for Phase 1 (13.1 hour ng mL?1) and Phase 2 (3075.2 hour ng mL?1).Conclusion and clinical relevanceConcurrent administration of CYP inhibitors with methadone significantly increased the area under the curve and plasma concentrations of methadone after oral administration to dogs. Further studies are needed assessing more clinically relevant combinations of methadone and CYP inhibitors.  相似文献   

15.
ObjectiveTo determine the possible additive effect of midazolam, a GABAA agonist, on the end-tidal concentration of isoflurane that prevents movement (MACNM) in response to noxious stimulation.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult intact male, mixed-breed dogs.MethodsAfter baseline isoflurane MACNM (MACNM-B) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg?1 and constant rate infusion (CRI) (2.5 μg kg?1 minute?1) (LDL), followed by an Ld (0.4 mg kg?1) and CRI (5 μg kg?1 minute?1) (LDH). The MDS was an Ld (0.8 mg kg?1) and CRI (10 μg kg?1 minute?1) (MDL) followed by an Ld (1.6 mg kg?1) and CRI (20 μg kg?1 minute?1) (MDH). The HDS was an Ld (3.2 mg kg?1) and CRI (40 μg kg?1 minute?1) (HDL) followed by an Ld (6.4 mg kg?1) and CRI (80 μg kg?1 minute?1) (HDH). MACNM was re-determined after each dose in each series (MACNM-T).ResultsThe median MACNM-B was 1.42. MACNM-B did not differ among groups (p >0.05). Percentage reduction in MACNM was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MACNM reduction (r = 0.36).Conclusion and clinical relevanceMidazolam doses in the range of 10–80 μg kg?1 minute?1 significantly reduced the isoflurane MACNM. However, doses greater than 10 μg kg?1 minute?1 did not further decrease MACNM indicating a ceiling effect.  相似文献   

16.
ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg?1 IM) and group MA (n = 14) medetomidine (20 μg kg?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg?1 hour?1 alfaxalone IV and infusion adjusted (±0.5 mg kg?1 hour?1) every five minutes according to alterations in heart rate (HR), respiratory rate (fR), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg?1) or if fR >40 breaths minute?1 (0.25 mg kg?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg?1 hour?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL?1. In group MA, fR, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg?1 hour?1.  相似文献   

17.
Propofol anaesthesia for surgery in late gestation pony mares   总被引：2，自引：0，他引：2  
Objective To characterize propofol anaesthesia in pregnant ponies. Animals Fourteen pony mares, at 256 ± 49 days gestation, undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (20 µg kg?1), butorphanol (20 µg kg?1) and detomidine (10 µg kg?1) was given 30 minutes before induction of anaesthesia with detomidine (10 µg kg?1) and ketamine (2 mg kg?1) IV Maternal arterial blood pressure was recorded (facial artery) throughout anaesthesia. Arterial blood gas values and plasma concentrations of glucose, lactate, cortisol and propofol were measured at 20‐minute intervals. Anaesthesia was maintained with propofol infused initially at 200 µg kg?1 minute?1, and at 130–180 µg kg?1 minute?1 after 60 minutes, ventilation was controlled with oxygen and nitrous oxide to maintain PaCO2 between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg) and PaO2 between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia flunixin (1 mg kg?1), procaine penicillin (6 IU) and butorphanol 80 µg kg?1 were given. Lactated Ringer's solution was infused at 10 mL kg?1 hour?1. Simultaneous fetal and maternal blood samples were withdrawn at 85–95 minutes. Recovery from anaesthesia was assisted. Results Arterial blood gas values remained within intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5–9.1 µg kg?1); disposition estimates were clearance 6.13 ± 1.51 L minute?1 (mean ± SD) and volume of distribution 117.1 ± 38.9 L (mean ± SD). Plasma cortisol increased from 193 ± 43 nmol L?1 before anaesthesia to 421 ± 96 nmol L?1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal umbilical venous pH, PO2 and PCO2 were 7.35 ± 0.04, 6.5 ± 0.5 kPa (49 ± 4 mm Hg) and 6.9 ± 0.5 kPa (52 ± 4 mm Hg); fetal arterial pH, PO2 and PCO2 were 7.29 ± 0.06, 3.3 ± 0.8 kPa (25 ± 6 mm Hg) and 8.7 ± 0.9 kPa (65 ± 7 mm Hg), respectively. Recovery to standing occurred at 46 ± 17 minutes, and was generally smooth. Ponies regained normal behaviour patterns immediately. Conclusions and clinical relevance Propofol anaesthesia was smooth with satisfactory cardiovascular function in both mare and fetus; we believe this to be a suitable anaesthetic technique for pregnant ponies.  相似文献   

18.
ObjectiveTo report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols.Study designProspective, randomized clinical study.AnimalsTwenty client-owned dogs presenting for elective ovariohysterectomy or castration.MethodsThe dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg?1) and hydromorphone (0.1 mg kg?1) IM approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg?1) IV to effect and in dogs in group 2 with diazepam (0.2 mg kg?1) IV followed by etomidate (2 mg kg?1) IV to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5–4%) and group 2 received a combination of fentanyl (0.8 μg kg?1 minute?1) and midazolam (8.0 μg kg?1 minute?1) IV plus sevoflurane (adjustable vaporizer setting 0.5–4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively.ResultsBaseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma.Conclusions and clinical relevanceThere was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.  相似文献   

19.
Objectives To study in horses (1) the relationship between cardiovascular variables and muscle perfusion during propofol–ketamine anaesthesia, (2) the physiological effects of a single intravenous (IV) detomidine injection, (3) the metabolic response of muscle to anaesthesia, and (4) the effects of propofol–ketamine infusion on respiratory function. Study design Prospective experimental study. Animals Seven standardbred trotters, 5–12 years old, 416–581 kg. Methods Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg?1) and maintained with a continuous IV infusion of propofol (0.15 mg kg?1 minute?1) and ketamine (0.05 mg kg?1 minute?1) with horses positioned in left lateral recumbency. After 1 hour, detomidine (0.01 mg kg?1) was administered IV and 40–50 minutes later anaesthesia was discontinued. Cardiovascular and respiratory variables (heart rate, cardiac output, systemic and pulmonary artery blood pressures, respiratory rate, tidal volume, and inspiratory and expiratory O2 and CO2) and muscle temperature were measured at pre‐determined times. Peripheral perfusion was measured continuously in the gluteal muscles and skin using laser Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal muscles were analysed for glycogen, creatine phosphate, creatine, adenine nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for PO2, PCO2, pH, oxygen saturation and HCO3. Mixed venous blood was analysed for PO2, PCO2, pH, oxygen saturation, HCO3, cortisol, lactate, uric acid, hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase, electrolytes, total protein, haemoglobin, haematocrit and white blood cell count. Results Circulatory function was preserved during propofol–ketamine anaesthesia. Detomidine caused profound hypertension and bradycardia and decreased cardiac output and muscle perfusion. Ten minutes after detomidine injection muscle perfusion had recovered to pre‐injection levels, although heart rate and cardiac output had not. No difference in indices of muscle metabolism was found between dependent and independent muscles. Anaerobic muscle metabolism, indicated by decreased muscle and creatine phosphate levels was evident after anaesthesia. Conclusion Muscle perfusion was closely related to cardiac output but not arterial blood pressure. Total intravenous anaesthesia with propofol–ketamine deserves further study despite its respiratory depression effects, as the combination preserves cardiovascular function. Decreases in high‐energy phosphate stores during recovery show that muscle is vulnerable after anaesthesia. Continued research is required to clarify the course of muscle metabolic events during recovery.  相似文献   

20.
Objective To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations. Design Randomized experimental study. Animals Six healthy 3‐year‐old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D). Methods Goats were given IV and IM butorphanol (0.1 mg kg?1) using a randomized cross‐over design with a 1‐week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [VdSS], systemic clearance [ClTB], extrapolated peak plasma concentration [C0] or estimated peak plasma concentration [CMAX], time to estimated peak plasma concentration [TMAX], distribution and elimination half‐lives [t1/2], and bioavailability) were calculated. Behavior was subjectively scored. A two‐tailed paired t‐test was used to compare the elimination half‐lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant. Results Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg?1, and ClTB was 0.0096 ± 0.0024 L kg?1 minute?1. Extrapolated C0 of butorphanol after IV administration was 146.5 ± 49.8 ng mL?1. Estimated CMAX after IM administration of butorphanol was 54.98 ± 14.60 ng mL?1, and TMAX was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half‐life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg?1, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half‐life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.  相似文献   

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