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1.
ObjectiveTo evaluate the pharmacokinetics, in dogs, of liposome–encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).AnimalsFour healthy purpose–bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg.Study designRandomized cross–over design.MethodsEach dog was given either 4.0 mg kg?1 of ASG–oxymorphone or 8.0 mg kg?1 of ASG–hydromorphone SC on separate occasions with a 3–month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC–MS and pharmacokinetic parameters were calculated using commercial software and non–compartmental methods.ResultsSerum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG–oxymorphone was 7.5 ng mL?1; Cmax for ASG–hydromorphone was 5.7 ng mL?1.Conclusions and clinical relevanceOxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.  相似文献   

2.
ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg–1 hour–1; group D; 12 horses); dexmedetomidine (1.0 μg kg–1 hour–1) and butorphanol bolus (0.05 mg kg–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg–1 hour–1) and remifentanil (3.0 μg kg–1 hour–1; group DR; 13 horses); or ketamine (0.6 mg kg–1 hour–1) and morphine (0.15 mg kg–1, 0.1 mg kg–1 hour–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.  相似文献   

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4.
ObjectiveTo characterize the pharmacokinetics of vatinoxan in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsA group of six adult healthy male neutered cats.MethodsCats were anesthetized using isoflurane in oxygen. Venous catheters were placed to administer the drug and sample blood. Vatinoxan, 1 mg kg–1, was administered intravenously over 5 minutes. Blood was sampled before and at various times during and up to 8 hours after vatinoxan administration. Plasma vatinoxan concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time–concentration data using population methods and nonlinear mixed effect modeling.ResultsA three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes (mL kg–1), the metabolic clearance and two distribution clearances (mL minute–1 kg–1) were 34 (55), 151 (35), 306 (18), 2.3 (34), 42.6 (25) and 5.6 (0), respectively. Hypotension increased the second distribution clearance to 10.6.Conclusion and clinical relevanceThe pharmacokinetics of vatinoxan in anesthetized cats were characterized by a small volume of distribution and a low clearance. An intravenous bolus of 100 μg kg–1 of vatinoxan followed by constant rate infusions of 55 μg kg–1 minute–1 for 20 minutes, then 22 μg kg–1 minute–1 for 60 minutes and finally 10 μg kg–1 minute–1 for the remainder of the infusion time is expected to maintain the plasma concentration within 90%–110% of the plasma vatinoxan concentration previously shown to attenuate the cardiovascular effects of dexmedetomidine (25 μg kg–1) in conscious cats.  相似文献   

5.
ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg?1 IV), l–methadone (0.1 mg kg?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.  相似文献   

6.
ObjectiveTo investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus).Study designA crossover design with an 11 day washout period.AnimalsA total of eight young male reindeer, aged 1.5–2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation.MethodsThe reindeer were administered meloxicam (0.5 mg kg–1 IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed.ResultsThe pharmacokinetic values, median (range), were determined. Elimination half-life (t½) with the IV route (n = 4) was 15.2 (13.2–16.8) hours, the volume of distribution at steady state was 133 (113–151) mL kg?1 and clearance was 3.98 (2.63–5.29) mL hour–1 kg–1. After oral administration (n = 7), the peak plasma concentration (Cmax) was detected at 6 hours, t½ was 19.3 (16.7–20.5) hours, Cmax 1.82 (1.17–2.78) μg mL–1 and bioavailability (n = 3) 49 (46–73)%. No evident adverse effects were detected after either administration route.Conclusions and clinical relevanceA single dose of meloxicam (0.5 mg kg–1 IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma.  相似文献   

7.
ObjectiveTo evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine–zolazepam–xylazine–tramadol.Study designProspective, experimental, randomized cross-over study.AnimalsEight Chinese miniature pigs (three females and five males) mean age 8 (range 7–10) months and bodyweight 57.5 (52.4–62.1) kg.MethodsAll animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg?1), xylazine (1.2 mg kg?1) and tramadol (1.6 mg kg?1) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg?1), FLU (0.1 mg kg?1), NAL (0.03 mg kg?1), ATI–FLU, FLU–NAL, ATI–NAL or ATI–FLU–NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey’s test to compare differences between means, or by Kruskal–Wallis test as appropriate.ResultsFLU, NAL alone, or FLU–NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam–xylazine–tramadol. ATI, ATI–FLU, ATI–NAL and ATI–FLU–NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI–FLU–NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study.Conclusion and clinical relevanceATI–FLU–NAL is the most effective combination for antagonizing tiletamine/zolazepam–xylazine–tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.  相似文献   

8.
ObjectiveTo investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs.Study designExperimental, balanced, block randomized, two-group design.AnimalsA group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old.MethodsDeltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg–1 hour–1 or fentanyl 5, 10, 20, 40, 80 and 160 μg kg–1 hour–1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%.ResultsNWR AUC increased at fentanyl 5 μg kg–1 hour–1 but decreased at fentanyl 40, 80 and 160 μg kg–1 hour–1 and dexmedetomidine 4.0 and 8.0 μg kg–1 hour–1. All pigs at fentanyl 80 μg kg–1 hour–1, and three pigs at dexmedetomidine 8.0 μg kg–1 hour–1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg–1 hour–1 but decreased at dexmedetomidine 2, 4 and 8 μg kg–1 hour–1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed.Conclusion and clinical relevanceIf anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.  相似文献   

9.
ObjectiveTo compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses.Study designRandomized controlled clinical trial.AnimalsA total of 40 adult horses admitted for elective arthroscopy.MethodsHorses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg–1; group TxH; n = 19) or butorphanol (0.02 mg kg–1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography–tandem mass spectrometry. Data were analyzed with a mixed-effect model.ResultsMedian (range) baseline EQUUS-FAP was 1.2 (0.0–4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0–10.0), increased at P2 [4.5 (0–10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0–11.0)]. Group TxB baseline CPS was 2.0 (0.0–8.0), increased at P2 [3.5 (0.0–11.0); p = 0.009] and P4 [5.0 (0.0–11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL–1, clearance was 30.7 ± 7.23 mL minute–1 kg–1 and volume of distribution at steady state was 884 ± 740 mL kg–1.ConclusionsHydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery.Clinical relevanceHydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.  相似文献   

10.
ObjectiveTo determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs.Study designProspective, crossover, randomized experimental study.AnimalsA group of nine healthy Beagle dogs.MethodsAcetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg–1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 μg kg–1) intramuscularly, anaesthesia was induced with propofol (2–3 mg kg–1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe′Iso 1.3–1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05).ResultsA two-compartmental model best described time–concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94–3.65) and 1.72 (0.89–2.60) L kg–1, clearance values 1.52 (0.71–2.30) and 1.60 (0.91–1.78) L kg–1 hour–1 or terminal elimination half-life values 2.45 (1.45–8.71) and 3.57 (1.96–6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded.Conclusions and clinical relevanceIV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.  相似文献   

11.
ObjectiveTo evaluate the pharmacodynamic effects and pharmacokinetics of a single intramuscular (IM) injection of alfaxalone in central bearded dragons (Pogona vitticeps) when injected at a cranial versus a caudal site.Study designProspective, masked, randomized crossover study.AnimalsA total of 13 healthy bearded dragons weighing 0.48 ± 0.1 kg.MethodsAlfaxalone (10 mg kg–1) was administered IM to 13 bearded dragons in the triceps muscle (cranial treatment) or the quadriceps muscle (caudal treatment) separated by 4 weeks. Pharmacodynamic variables included movement score, muscle tone score and righting reflex. Blood was obtained from the caudal tail vein using a sparse sampling methodology. Plasma alfaxalone concentrations were determined using liquid chromatography–mass spectrometry, and pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Differences in variables between injection sites were analyzed using a nonparametric Wilcoxon signed-rank test for paired data with significance set at p ≤ 0.05.ResultsTime to loss of righting reflex score was not different, median (interquartile range), between cranial and caudal treatments [8 (5–11) and 8 (4–12) minutes, respectively, p = 0.72]. Time to recovery of righting reflex was also not different between cranial and caudal treatments [80 (44–112) and 64 (56–104) minutes, respectively, p = 0.75]. Plasma alfaxalone concentrations were not significantly different between treatments. The population estimate (95% confidence intervals) for volume of distribution per fraction absorbed was 1.0 (0.79–1.20) L kg–1, clearance per fraction absorbed was 9.6 (7.6–11.6) mL minute–1 kg–1, absorption rate constant was 2.3 (1.9–2.8) minute–1 and elimination half-life was 71.9 (52.7–91.1) minutes.Conclusions and clinical relevanceRegardless of the injection site, IM alfaxalone (10 mg kg–1) produced reliable chemical restraint in central bearded dragons, appropriate for nonpainful diagnostic procedures or anesthetic premedication.  相似文献   

12.
ObjectiveTo compare dexmedetomidine with acepromazine for premedication combined with methadone in dogs undergoing brachycephalic obstructive airway syndrome (BOAS) surgery.Study designRandomized, blinded clinical study.AnimalsA group of 40 dogs weighing mean (± standard deviation) 10.5 ± 6 kg, aged 2.6 ± 1.9 years.MethodsDogs received either acepromazine 20 μg kg–1 (group A) or dexmedetomidine 2 μg kg–1 (group D) intramuscularly with methadone 0.3 mg kg–1. Anaesthesia was induced with propofol and maintained with sevoflurane. Sedation (0–18), induction (0–6) and recovery (0–5) qualities were scored. Propofol dose, hypotension incidence, mechanical ventilation requirement, extubation time, additional sedation, oxygen supplementation, regurgitation and emergency intubation following premedication or during recovery were recorded. Data were analysed using t tests, Mann-Whitney U or Chi-square tests.ResultsGroup A dogs were less sedated [median (range): 1.5 (0–12)] than group D [5 (1–18)] (p = 0.021) and required more propofol [3.5 (1–7) versus 2.4 (1–8) mg kg–1; p = 0.018]. Induction scores [group A: 5 (4–5); group D 5 (3–5)] (p = 0.989), recovery scores [group A 5 (4–5); group D 5(3–5)](p = 0.738) and anaesthesia duration [group A:93 (50–170); group D 96 (54–263) minutes] (p = 0.758) were similar between groups. Time to extubation was longer in group A 12.5 (3-35) versus group D 5.5 (0–15) minutes; (p = 0.005). During recovery, two dogs required emergency intubation (p > 0.99) and five dogs required additional sedation (p > 0.99). Oxygen supplementation was required in 16 and 12 dogs in group A and D, respectively (p = 0.167); no dogs in group A and one dog in group D regurgitated (p = 0.311).Conclusions and clinical relevanceDexmedetomidine 2 μg kg–1 produces more sedation but similar recovery quality to acepromazine 20 μg kg–1 combined with methadone in dogs undergoing BOAS surgery.  相似文献   

13.
ObjectiveTo determine if general anesthesia with sevoflurane and laparoscopic surgery changed gastric and small bowel propulsive motility or pH in dogs.Study designProspective, controlled trial.AnimalsTwelve, 19–24 months old, female, Treeing Walker Hound dogs, weighing 23–30 kg.MethodsDogs were anesthetized for a median of 8.5 hours during another study to determine the minimum alveolar concentration of sevoflurane using a visceral stimulus. Gastric and small bowel motility were determined using a sensor capsule that measures pressure, pH and temperature. Gastric transit time and motility index were calculated. For 8/12 dogs, gastric motility, pH and transit time were measured. In 4/12 dogs, small bowel motility and pH were measured.ResultsAnesthesia decreased gastric and small bowel motility but did not change luminal pH. Mean gastric contraction force decreased from median (range) 11 (8–20) to 3 (1–10) mmHg (p < 0.01) and gastric motility index decreased from 0.63 (0–1.58) to 0 (0–0.31; p = 0.01). Frequency of contractions did not change, 3.7 (1.6–4.4) versus 2.8 (0.1–5.1) contractions minute?1 (p = 0.1). Gastric motility returned to normal 12–15 hours following anesthesia. Gastric emptying was prolonged from 12 (5.3–16) to 49 (9.75–56.25) hours (p < 0.01). Mean small bowel contraction force decreased from 34 (24–37) to 3 (0.9–17) mmHg (p < 0.02) and motility index decreased from 3.75 (1–4.56) to 0 (0–1.53; p = 0.02). Frequency of contractions did not change, 0.5 (0.3–1.4) versus 1.4 (0.3–4.6) contractions minute?1 (p = 0.11). Small bowel motility returned within 2 hours after anesthesia. Laparoscopy did not result in changes to gastric or small bowel parameters beyond those produced by general anesthesia.Conclusions and clinical relevanceThe force of gastric and small bowel contractions decreased during sevoflurane anesthesia for laparoscopy. Although gastric motility returned to normal within 12–15 hours the impairment of gastric emptying lasted 30–40 hours, predisposing dogs to postoperative ileus.  相似文献   

14.
ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg–1 MED loading dose, followed by a 1.7 μg kg–1 hour–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg–1 hour–1 compared to SAL 3 (1.8–5.3) μg kg–1 hour–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.  相似文献   

15.
ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs.Study designRandomized crossover experimental study.AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg.MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg–1 hour–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg–1 hour–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg–1 minute–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg–1 hour–1, obtained using log-linear regression analysis.ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg–1 hour–1.Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.  相似文献   

16.
ObjectiveTo evaluate the effects and utility of tiletamine–zolazepam–medetomidine (TZM) and ketamine–medetomidine (KM) for anesthesia of Amur leopard cats (Prionailurus bengalensis euptailurus).Study designProspective, randomized experimental trial.AnimalsA total of six female (3.70 ± 0.49 kg) and six male (5.03 ± 0.44 kg; mean ± standard deviation) Amur leopard cats aged 2–6 years.MethodsEach animal was administered four protocols separated by ≥3 weeks. Each protocol included medetomidine (0.05 mg kg–1) combined with tiletamine–zolazepam (1 mg kg–1; protocol MTZLO); tiletamine–zolazepam (2 mg kg–1; protocol MTZHI); ketamine (2 mg kg–1; protocol MKLO); or ketamine (4 mg kg–1; MKHI) administered intramuscularly. At time 0 (onset of lateral recumbency) and 30 minutes, heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and hemoglobin oxygen saturation (SpO2) were recorded. Times to onset of lateral recumbency, duration of anesthesia and time to standing were recorded.ResultsOverall, animals were anesthetized with all protocols within 10 minutes, anesthesia was maintained ≥57 minutes, and recovery (time from the first head lift to standing) was completed within 5 minutes. During anesthesia with all protocols, HR, fR, rectal temperature, SpO2 and MAP were 99–125 beats minute–1, 33–44 breaths minute–1, 37.6–39.4 °C, 90–95% and 152–177 mmHg, respectively. No adverse event was observed.Conclusions and clinical relevanceTZM and KM at various dosages resulted in rapid onset of anesthesia, duration of >57 minutes and rapid recovery without administration of an antagonist. Accordingly, all these combinations are useful for anesthetizing Amur leopard cats and for performing simple procedures. However, the low doses of the anesthetic agents are recommended because there was no difference in duration of anesthesia between the dose rates studied.  相似文献   

17.
ObjectiveTo evaluate the effects of dexmedetomidine alone or in combination with different opioids on intraocular pressure (IOP) in dogs.Study designExperimental, prospective, crossover, randomized, blinded study.AnimalsA total of six Beagle dogs (two males and four females) aged 2 years and weighing 15.9 ± 2.9 kg (mean ± standard deviation).MethodsDogs were distributed randomly into seven treatments (n = 6 per treatment) and were administered dexmedetomidine alone (10 μg kg–1; Dex) or in combination with butorphanol (0.15 mg kg–1; DexBut), meperidine (5 mg kg–1; DexMep), methadone (0.5 mg kg–1; DexMet), morphine (0.5 mg kg–1; DexMor), nalbuphine (0.5 mg kg–1; DexNal) or tramadol (5 mg kg–1; DexTra). All drugs were administered intramuscularly. IOP was measured before drug injection (time 0, baseline) and every 15 minutes thereafter for 120 minutes (T15–T120).ResultsThere were significant reductions in IOP compared with baseline in treatments Dex and DexMep at times T30–T120, and in treatment DexMet at T15–T90. IOP decreased compared with baseline in treatments DexBut, DexNal and DexTra at all evaluation times. No changes in IOP were seen in treatment DexMor. The mean IOP values in treatment DexMet at T105–T120 were higher than those for other treatments.Conclusions and clinical relevanceDexmedetomidine alone or in combination with butorphanol, meperidine, methadone, nalbuphine or tramadol resulted in decreased IOP for 120 minutes in dogs. The magnitude of the reduction was small and lacked clinical significance.  相似文献   

18.
ObjectiveNon-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E2 receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma.Study designExperimental study.AnimalsA total of six healthy, adult mixed-breed mares weighing 502 ± 66 (397–600) kg and aged 14.8 ± 5.3 (6–21) years.MethodsMares were administered one dose of 2 mg kg–1 grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography.ResultsGrapiprant plasma concentrations ranged from 71 to 149 ng mL–1 with the mean peak concentration (106 ng mL–1) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL–1) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL–1 and were still detectable at 48 hours after administration.Conclusions and clinical relevanceCurrently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114–164 ng mL–1. Oral administration of grapiprant (2 mg kg–1) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.  相似文献   

19.
ObjectiveTo investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids.Study designExperimental prospective study.AnimalsA total of 18 (n = 6 animals per experiment) male Saanen goat kids (2–4 weeks old).MethodsThe study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg–1). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg–1 minute–1). Data are shown as mean ± standard deviation.ResultsThe mean terminal half-life (t1/2λz), mean volume of distribution at steady state (Vdss) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg–1 and 5.33 L hour–1 kg–1, respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL–1 at 0.22 hour and its mean t1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg–1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL–1, respectively.ConclusionsIntravenous administration of 8 mg kg–1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding.Clinical relevanceArticaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids.  相似文献   

20.
ObjectiveTo describe ketamine–propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits.Study designRandomized, crossover experimental study.AnimalsA total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg).MethodsRabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg–1) in combination with medetomidine (0.1 mg kg–1), midazolam (1 mg kg–1) or morphine (1 mg kg–1), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL–1) and propofol (5 mg mL–1) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg–1 minute–1 (0.2 mg kg–1 minute–1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded.ResultsKetofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg–1) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg–1 minute–1, respectively) than in treatment Saline (1.2 ± 0.2 mg kg–1 minute–1) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation.Conclusions and clinical relevancePremedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits.  相似文献   

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