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Luiz Cesar P Santos John W Ludders Hollis N Erb Karen L Basher Pati Kirch Robin D Gleed 《Veterinary anaesthesia and analgesia》2010,37(5):417-424
ObjectiveTo determine if buprenorphine plus dexmedetomidine administered via the oral transmucosal route produces sufficient sedation in cats so that students can insert intravenous catheters.Study DesignProspective, randomized, blinded, clinical trial.AnimalsEighty‐seven shelter‐owned female cats aged 4–48 months, weighing 1.1–4.9 kg.MethodsCats were randomly allocated to two treatment groups based on route of drug administration: oral transmucosal (OTM), or intramuscular (IM). Buprenorphine (20 μg kg?1) plus dexmedetomidine (20 μg kg?1) were administered as pre‐medicants via one of these two routes. Prior to and 20 minutes after drug administration, heart and respiratory rates, systolic arterial pressure, and posture were measured and recorded. Twenty minutes after drug administration the same variables plus each cat’s response to clipper sound, clipping, and restraint were recorded; higher scores indicated more sedation.ResultsThere were no significant differences between the two groups prior to pre‐medication. Within each treatment group heart rate was significantly lower 20 minutes after treatment, but it did not differ significantly between the two groups. Twenty minutes after treatment, respiratory rate was significantly less in the OTM group, but did not differ significantly between the two groups. Systolic arterial pressure did not differ within or between the two groups at either time. Scores for posture increased significantly within both groups, and cats in the IM group had higher scores after treatment. Twenty minutes after treatment, cats in the IM group had higher scores for clipping and restraint than OTM cats. Ketamine (IM) was necessary to facilitate catheterization in 25% and 16% of cats in the OTM and IM groups, respectively, but this was not significantly different.Conclusions and clinical relevanceAdministration of dexmedetomidine plus buprenorphine by the OTM route is easy to perform, but produces less sedation than the IM route for IV catheterization in cats. 相似文献
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James R Hunt Nicola J Grint Polly M Taylor Joanna C Murrell 《Veterinary anaesthesia and analgesia》2013,40(3):297-307
ObjectiveTo evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery.Study designProspective, randomized, blinded clinical study.AnimalsForty dogs and 48 cats.MethodsAnimals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg?1 with either dexmedetomidine (dex) 250 μg m?2 or acepromazine (acp) 0.03 mg kg?1, followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall–Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005).ResultsCats premedicated with dex were more sedated than cats premedicated with acp (p < 0.001) and ALF doses were lower in dex cats (1.2 ± 1.0 mg kg?1) than acp cats (2.5 ± 1.9 mg kg?1) (p = 0.041). There were no differences in sedation in dogs however PRO doses were lower in dex dogs (1.5 ± 0.8 mg kg?1) compared to acp dogs (3.3 ± 1.1 mg kg?1) (p < 0.001). There were no differences between groups with respect to pain scores or MNT for cats or dogs.ConclusionChoice of dex or acp, when given with buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia.Clinical relevanceA combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent. 相似文献
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Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats
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N. Porters H. de Rooster T. Bosmans K. Baert M. Cherlet S. Croubels P. De Backer I. Polis 《Journal of veterinary pharmacology and therapeutics》2015,38(2):203-208
Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1‐month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24‐h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography–tandem mass spectrometry. Plasma concentration–time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration–time curve (AUC) and the maximum plasma concentrations (Cmax) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site. 相似文献
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Louisa S Slingsby Joanna C Murrell Polly M Taylor 《Veterinary anaesthesia and analgesia》2010,37(2):162-170
ObjectiveTo evaluate the sedative and antinociceptive effects of combinations of dexmedetomidine and buprenorphine in cats.Study designExperimental randomized study.AnimalsTwelve purpose-bred neutered domestic short-hair cats (4 male and 8 female) weighing 4.6 kg (range 3.7–5.5 kg) aged from 2 to 5 years.MethodsSix cats per group were administered buprenorphine (B) at 10 (B10) or 20 μg kg?1 (B20) or dexmedetomidine (D) at 20 (D20) or 40 μg kg?1 (D40) or a combination of B10/D20. A feline thermal nociceptive threshold testing device was used to evaluate the antinociceptive effects of the drugs before and up to 24 hours after drug treatment. Sedation was scored using a 100 mm visual analogue scale (VAS).ResultsThermal thresholds increased significantly after administration of all but D20. Area under the curve (AUC, hours °C) for the first 6 hours (mean ± SD) for B20 (281 ± 17.8) was significantly greater than B10 (260 ± 11.4), D20 (250 ± 7.9) and D40 (255 ± 11.4). The AUC for B10/D20 (273 ± 12.2) was significantly greater than D20 but not the other treatments. No sedation was seen after administration of B10 or B20 and maximal sedation was seen for all animals in the D40 and B10/D20 groups and most animals in the D20 group.ConclusionsD20 alone had the smallest analgesic effect; B10 alone provided no sedation but their combination gave good sedation with analgesia comparable with B20.Clinical relevanceThis combination could be a useful multimodal sedative/analgesic regimen in cats. 相似文献
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Bruno H. Pypendop Juhana Honkavaara Jan E. Ilkiw 《Veterinary anaesthesia and analgesia》2017,44(4):823-831
Objective
To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.Study design
Prospective randomized crossover experimental study.Animals
A total of eight healthy adult male castrated cats aged 1–2 years.Methods
Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data.Results
A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM.Conclusions and clinical relevance
MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM. 相似文献8.
Kristine T. Siao Bruno H. Pypendop Juhana Honkavaara Jan E. Ilkiw 《Veterinary anaesthesia and analgesia》2017,44(5):1101-1115
Objective
To characterize the hemodynamic effects of dexmedetomidine, with or without MK-467, following intramuscular (IM) administration in cats.Study design
Randomized, crossover, experimental study.Animals
Six healthy adult male castrated purpose-bred cats.Methods
Cats were anesthetized with isoflurane in oxygen and instrumented. Cats were administered dexmedetomidine (25 μg kg?1), with (DM) or without (D) MK-467 (600 μg kg?1), IM in the epaxial muscles. Cardiovascular variables, respiratory variables, temperature, and arterial and mixed-venous pH, blood gases and electrolytes were measured prior to drug administration and at various time points for 6 hours thereafter, during anesthesia with isoflurane. Additional variables were calculated from the measurements, using standard equations. Results were analyzed with a two-way repeated-measures analysis of variance, followed by Dunnett’s and paired t tests where appropriate.Results
Dexmedetomidine resulted in a significant decrease in cardiac index (CI) and significant increases in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). The addition of MK-467 failed to prevent most of the early cardiovascular effects of dexmedetomidine, but the duration of systemic vasoconstriction was shorter and CI did not decrease. The lowest and highest post-treatment values in each treatment were 0.1 ± 0.03 and 0.13 ± 0.03 L minute?1 BW?0.67 (D) versus 0.14 ± 0.01 and 0.19 ± 0.03 L minute?1 BW?0.67 (DM) for CI, 87 ± 13 and 181 ± 21 mmHg (D) versus 70 ± 11 and 153 ± 18 mmHg (DM) for MAP and 58,948 ± 17,754 and 119,432 ± 40,423 dynes second cm?5 BW?0.67 (D) versus 25,870 ± 3782 and 76,498 ± 17,258 dynes second cm?5 BW?0.67 (DM) for SVRI, respectively.Conclusion and clinical relevance
IM coadministration of MK-467 and dexmedetomidine in isoflurane-anesthetized cats shortened dexmedetomidine-induced cardiovascular effects. This drug combination may be useful in cats in which longer-lasting hypertension and hemodynamic depression is of concern. 相似文献9.
Bruno H. Pypendop Juhana Honkavaara Jan E. Ilkiw 《Veterinary anaesthesia and analgesia》2017,44(1):52-62
Objective
To characterize the cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous (IV) administration in cats.Study design
Prospective Latin square experimental study.Animals
Six healthy adult purpose-bred cats.Methods
Cats were anesthetized with desflurane in oxygen for instrumentation with a carotid artery catheter and a thermodilution catheter in the pulmonary artery. One hour after discontinuation of desflurane, cats were administered dexmedetomidine (25 μg kg–1), MK-467 (600 μg kg–1), or dexmedetomidine (25 μg kg–1) and MK-467 (600 μg kg–1). All treatments were administered IV as a bolus. Cardiovascular variables were measured prior to drug administration and for 8 hours thereafter. Only data from the dexmedetomidine and dexmedetomidine–MK-467 treatments were analyzed.Results
Dexmedetomidine produced significant decreases in heart rate, cardiac index and right ventricular stroke work index, and significant increases in arterial blood pressure, central venous pressure, pulmonary artery pressure and systemic vascular resistance index. Dexmedetomidine combined with MK-467 resulted in significant but transient decrease in blood pressure and right ventricular stroke work index.Conclusion and clinical relevance
Following IV co-administration, MK-467 effectively attenuated dexmedetomidine-induced cardiovascular effects in cats. The drug combination resulted in transient reduction in arterial blood pressure, without causing hypotension. 相似文献10.
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Federica Di Cesare Daniela Gioeni Giuliano Ravasio Alberto Pellegrini Lorena Lucatello Vittoria Bisutti Roberto Villa Petra Cagnardi 《Journal of veterinary pharmacology and therapeutics》2019,42(4):392-400
This study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client‐owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 μg/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) Cmax values of 0.82 (0.42–1.49) ng/ml and 13.22 (2.80–52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and Cmax values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended. 相似文献
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Granholm M McKusick BC Westerholm FC Aspegrén JC 《Veterinary anaesthesia and analgesia》2006,33(4):214-223
OBJECTIVE: To evaluate and compare the clinical effects of dexmedetomidine (DEX) and medetomidine (MED) in cats, and their reversal with atipamezole (ATI). Study design Prospective blinded randomized multi-centre clinical trial. Animals One hundred and twenty client-owned cats. METHODS: Cats were randomly allocated to receive a single intramuscular (IM) injection of either DEX (0.04 mg kg(-1), n = 62) or MED (0.08 mg kg(-1), n = 58) for minor procedures requiring sedation and analgesia. Afterwards, ATI (0.2 mg kg(-1)) was administered IM to half the cats, randomly assigned. Prior to, during and after the procedure the sedative, analgesic and cardiorespiratory effects and body temperature were assessed. RESULTS: Dexmedetomidine and MED produced clinically and statistically comparable effects. The intended procedure(s) could be performed in over 90% of cats. Sedation and analgesia were apparent within 5 minutes, peak effects were observed at approximately 30 minutes and spontaneous recovery occurred by 180 minutes of injection. Heart and respiratory rate and body temperature decreased significantly over time and had not returned to baseline values 180 minutes after administration. ATI administration completely reversed the sedative and analgesic effects, returned the heart rate to normal and prevented any further reductions in respiratory rate and body temperature in both DEX- and MED-treated cats. The reporting of adverse events was low and the most commonly observed event was vomiting (7%). No serious adverse events or concerns regarding safety were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (0.04 mg kg(-1)) produced comparable sedative and analgesic effects to MED (0.08 mg kg(-1)) in cats. DEX produced adequate sedation and analgesia for radiography, grooming, dental care and lancing of abscesses. ATI fully reversed the clinical effects of DEX. 相似文献
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Carolyn M. Doerning Michael P. Bradley Patrick A. Lester Megan H. Nowland 《Veterinary anaesthesia and analgesia》2018,45(5):658-666
Objective
To characterize alfaxalone administered subcutaneously (SC) in guinea pigs, both alone and in combination with dexmedetomidine and buprenorphine.Study design
Prospective, blinded, crossover study.Animals
A total of 15 healthy female guinea pigs weighing 400–600 g.Methods
Alfaxalone (10, 20 and 40 mg kg?1) was administered SC to three guinea pigs as a pilot dose-finding study. Alfaxalone (20 mg kg?1; A20) was selected for comparison against combination protocols of alfaxalone (15 and 20 mg kg?1) with dexmedetomidine (0.25 mg kg?1) and buprenorphine (0.05 mg kg?1; A15DB, A20DB). Each protocol was randomly administered to 12 guinea pigs separated by ≥7 days. Time and quality of induction and recovery, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, pedal withdrawal reflex and adverse effects were recorded.Results
The median time to induction for A20, A15DB and A20DB was 6.8–8.0 minutes with no significant difference between treatments. Mean duration of recumbency for A20 was 73.6 ± 19.6 minutes. Recumbency duration for A15DB and A20DB extended to 90 minutes, at which time dexmedetomidine was antagonized using atipamezole (0.025 mg kg?1 SC). Physiological variables were within normal limits with the exception of one animal that died 45 minutes following treatment with A20DB. Pedal withdrawal reflex remained intact with all treatments. Minor side effects such as twitching or bruxism occurred sporadically with treatment A20 but not with A15DB and A20DB.Conclusions and clinical relevance
SC alfaxalone produced uncomplicated sedation that may be recommended for nonpainful procedures that do not require complete immobility. The addition of dexmedetomidine and buprenorphine increased the duration of sedation and immobility, but did not result in general anesthesia. This combination sedation protocol may be useful for nonpainful procedures requiring extended immobility. 相似文献14.
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Niwako Ogata Teppei Kanda Mizuki Kawahata Takayasu Ichikawa Yuki Matsumoto Waka Morimitsu Yukiko Nishino Takamasa Itoi Kayo Furumoto 《Veterinary anaesthesia and analgesia》2017,44(5):1091-1100
Objective
To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (fR), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats.Study design
Randomized, blinded crossover study, with 1 week washout between treatments.Animals
Six healthy purpose-bred cats.Methods
Brimonidine tartrate ophthalmic solution 0.1% (one or two drops; 58.6 ± 3.3 μg per drop) or a control solution (artificial tear solution) was administered to six healthy cats. Behavioural observations and measurements of HR, fR, RT and MAP were recorded before and at 30, 60, 90, 120, 180, 240, 300 and 360 minutes after topical administration. Behavioural scores were analysed using Friedman’s test for repeated measures to evaluate the time effect in each treatment and treatment effect at each time point. Physiological variables (HR, fR, RT and MAP) were analysed using two-way analysis of variance for repeated measures to evaluate the time and treatment effects. The level of significance was set at p < 0.05.Results
Dose-dependent behavioural and physiological responses were noted. A dose of two drops of brimonidine resulted in sedation in the cats and decreased HR and MAP. Significant sedative effects occurred between 30 and 120 minutes and for physiological responses up to 360 minutes. The most frequent adverse reaction was vomiting, occurring within 40 minutes in all six cats administered two drops and five of the six cats administered one drop of brimonidine.Conclusions and clinical relevance
The results demonstrated that ocular administration of brimonidine 0.1% ophthalmic solution induced sedation in cats and some cardiovascular effects usually associated with α2-adrenoceptor agonists. Further studies should be performed to determine clinical applications for this agent in cats. 相似文献16.
OBJECTIVE: To describe the dose-related thermal antinociceptive effects of intravenous (i.v.) hydromorphone in cats. STUDY DESIGN: Randomized, blinded, crossover design. ANIMALS: Seven adult cats (3.5-7.4 kg), two spayed females, and five neutered males. METHODS: Hydromorphone (0.025, 0.05, or 0.1 mg kg(-1)) was administered i.v.. Skin temperature and thermal threshold were measured before and at selected time points to 720 minutes post-administration. Statistical analysis of mean thermal threshold and skin temperatures over time for each dose and between doses was by way of a split-plot model and post hoc Bonferroni t-tests. p < 0.05 was considered significant. RESULTS: A significant difference from baseline for mean thermal threshold was identified for the 0.05 mg kg(-1) dose (5-80 minutes, peak thermal threshold 46.9 +/- 6.2 degrees C) and 0.1 mg kg(-1) dose (5-200 minutes, peak thermal threshold 54.9 +/-0.2 degrees C). The thermal threshold was significantly greater after the 0.1 mg kg(-1) dose from 5 to 200 minutes compared to the 0.025 mg kg(-1) and 0.5 mg kg(-1) doses. The thermal threshold was significantly greater from 35 to 80 minutes for the 0.05 mg kg(-1) dose when compared with the 0.025 mg kg(-1) dose. Skin temperature was significantly increased from 35 to 140 minutes following the 0.1 mg kg(-1) dose. CONCLUSIONS: A dose-related antinociceptive effect was demonstrated for i.v. hydromorphone in cats. CLINICAL RELEVANCE: Hydromorphone at doses less than 0.1 mg kg(-1) has a modest antinociceptive effect and a short duration of action. At a dose of 0.1 mg kg(-1) i.v., onset of analgesia is rapid with a clinically useful duration of effect, but is associated with a rise in skin temperature. 相似文献
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《Veterinary anaesthesia and analgesia》2022,49(3):308-312
ObjectiveTo evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.Study designCrossover study (part 1) with observational study (part 2).AnimalsA total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12–16 weeks and weighing 2.8–3.5 kg in part 1. Separately, four additional rabbits in part 2.MethodsCrossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kg–1), or treatment DB, dexmedetomidine (0.1 mg kg–1) and buprenorphine (0.05 mg kg–1) intramuscularly. Anesthesia was induced with alfaxalone intravenously until a supraglottic airway device was placed to deliver 100% oxygen. Anesthesia was maintained with alfaxalone (TIVA). Infusion rates were adjusted to achieve an absent pedal withdrawal reflex. Heart rate, respiratory rate, noninvasive blood pressure, end-tidal carbon dioxide partial pressure and peripheral hemoglobin oxygen saturation (SpO2) were recorded every 5 minutes. Subsequently, four rabbits underwent ovariohysterectomy using treatment DB and alfaxalone TIVA.ResultsThe mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kg–1 hour–1 for treatments D and DB, respectively. In both treatments, blood pressure remained within acceptable range and SpO2 was > 95%. Postinduction apnea and respiratory depression were observed in both treatments and managed with manual positive pressure ventilation. Four separate rabbits underwent successful ovariohysterectomy with treatment DB and alfaxalone TIVA. One rabbit required supplementation with inhalant anesthesia; three rabbits were successfully maintained using alfaxalone TIVA alone.Conclusions and clinical relevancePremedication with dexmedetomidine–buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised. 相似文献
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Paulo VM Steagall Ludovic Pelligand Tatiana Giordano Christophe Auberger John W Sear Stelio PL Luna Polly M Taylor 《Veterinary anaesthesia and analgesia》2013,40(1):83-95
ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t1/2ke0 = 47.4 minutes) and receptor binding (kon = 0.011 mL ng?1 minute?1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats. 相似文献
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Robertson SA Lascelles BD Taylor PM Sear JW 《Journal of veterinary pharmacology and therapeutics》2005,28(5):453-460
The pharmacokinetics and thermal antinociceptive effects of buprenorphine after intravenous (i.v.) or oral transmucosal (OTM) administration were studied in six adult cats. Plasma buprenorphine concentrations were measured using radioimmunoassay in a crossover study after a dose of 20 microg/kg given by the i.v. or OTM route. Oral pH was measured. Blood for drug analyses was collected before, and at 1, 2, 4, 6, 10, 15, 30, and 60 min and at 2, 4, 6, 8, 12, and 24 h after treatment. Thermal thresholds were measured before treatment, then following treatment every 30 min to 6 h, every 1 hour to 12 h and at 24 hours postadministration. Plasma buprenorphine concentration effect relationships were analyzed using a log-linear effect model. Oral pH was 9 in each cat. Peak plasma buprenorphine concentration was lower and occurred later in the OTM group but median bioavailability was 116.3%. Thermal thresholds increased significantly between 30 and 360 min in both groups. Peak effect was at 90 min and there was no difference at any time between the two groups. There was distinct hysteresis between plasma drug concentration and effect in both groups. Overall, OTM administration of buprenorphine is as effective as i.v. treatment and offers a simple, noninvasive method of administration which produces thermal antinociception for up to 6 h in cats. 相似文献