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1.
ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg?1 and butorphanol tartrate 0.1 mg kg?1 IV and IM (MB), and MB combined with MK-467,500 μg kg?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (fR), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO2I) were calculated. After the follow-up period atipamezole 50 μg kg?1 IM was given to reverse sedation.ResultsHR, CI and DO2I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in fR between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.  相似文献   

2.
ObjectiveTo investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.Study designExperimental, crossover study with a 14 day wash-out period.AnimalsSeven healthy horses.MethodsThe horses received either detomidine (20 μg kg−1 IV) and butorphanol (20 μg kg−1 IV) alone (DET) or with MK-467 (200 μg kg−1 IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg−1) and midazolam (0.06 mg kg−1) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (PaO2/FiO2) and tissue oxygen delivery (DO2) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.ResultsThe induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and PaO2/FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.Conclusions and clinical relevanceMK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.  相似文献   

3.
ObjectiveTo investigate plasma drug concentrations and the effect of MK-467 (L-659′066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.Study designExperimental randomized blinded crossover study.AnimalsSix healthy horses.MethodsDetomidine (10 μg kg?1 IV) was administered alone (DET) and in combination with MK-467 (250 μg kg?1 IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed) and pharmacokinetic parameters. Significance was set at p < 0.05.ResultsA significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.Conclusions and clinical relevanceMK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.  相似文献   

4.
ObjectiveTo compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery.Study designProspective ‘blinded’ randomized clinical study.AnimalsTwenty-one healthy cats.MethodsCats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg?1 intravenously (IV) followed by boli (2 mg kg?1 IV); Group MK, induction with ketamine (5 mg kg?1 IV) after medetomidine (30 μg kg?1 intramuscularly (IM)], and maintenance with ketamine (2 mg kg?1 IV). Meloxicam (0.2 mg kg?1 IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0–24 points), a visual analogue scale (VAS 0–100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg?1 IM) was administered if CPS was scored =13. Data were analyzed using a general linear model, Kruskal–Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p < 0.05.ResultsVASs were significantly higher at 0.5, 1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and 12 hours in group MK. Post-operative MWT decreased significantly compared to baseline in both groups. There was no difference in CPS at any time point. Five cats required rescue analgesia (four in A; one in MK).Conclusion and clinical relevanceAnaesthesia with ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended.  相似文献   

5.
ObjectiveTo compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy.Study designRandomized, blinded clinical trial.AnimalsTwenty-one adult female cats (mean body weight: 3.1 ± 0.4 kg).MethodsCats received DEX (4 μg kg?1, IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg?1, n = 7), in GII cats were given epidural lidocaine (1 mg kg?1) + DEX (4 μg kg?1, n = 7), and in GIII cats were given epidural lidocaine (1 mg kg?1) + IV constant rate infusion (CRI) of DEX (0.25 μg kg?1 minute?1, n = 7). Variables evaluated included heart rate (HR), respiratory rate (fR), systemic arterial pressures, rectal temperature (RT), end-tidal CO2, end-tidal isoflurane concentration (e′ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, fR, RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. anova was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation.ResultsEpidural and CRI of DEX reduced HR during anesthesia maintenance. Mean ± SD e′ISO ranged from 0.86 ± 0.28% to 1.91 ± 0.63% in GI, from 0.70 ± 0.12% to 0.97 ± 0.20% in GII, and from 0.69 ± 0.12% to 1.17 ± 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI.Conclusions and clinical relevanceEpidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.  相似文献   

6.
ObjectiveTo evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses.Study designRandomized, crossover experimental study.AnimalsEight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years.MethodsBaseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2oAV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO2) and oxygen (PaO2) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg?1; group HIV), IM hyoscine (0.3 mg kg?1; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg?1) was administered IV and measurements were recorded at various time points for 130 minutes.ResultsMedetomidine induced bradycardia, 2oAV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2oAV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute?1 and 241 ± 37 mmHg versus 65 ± 16 beats minute?1 and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO2 and PaO2 were not significantly changed by administration of medetomidine with or without hyoscine.Conclusion and clinical relevanceHyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.  相似文献   

7.
ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (fR), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute⁻1 kg⁻1 and 1125 ± 309 mL kg⁻1. The t1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.  相似文献   

8.
ObjectiveTo evaluate the sedative effects of intravenous (IV) medetomidine (1 μg kg?1) and butorphanol (0.1 mg kg?1) alone and in combination in dogs.Study designProspective, blinded, randomized clinical trial.AnimalsSixty healthy (American Society of Anesthesiologists I) dogs, aged 6.2 ± 3.2 years and body mass 26 ± 12.5 kg.MethodsDogs were assigned to four groups: Group S (sodium chloride 0.9% IV), Group B (butorphanol IV), Group M (medetomidine IV) and Group MB (medetomidine and butorphanol IV). The same clinician assessed sedation before and 12 minutes after administration using a numerical scoring system in which 19 represented maximum sedation. Heart rate (HR), respiratory rate, pulse quality, capillary refill time and rectal temperature were recorded after each sedation score assessment. Sedation scores, sedation score difference (score after minus score before administration) and patient variables were compared using one-way anova for normally distributed variables and Kruskal–Wallis test for variables with skewed distributions and/or unequal variances. Where significance was found, further evaluation used Bonferroni multiple comparisons for pair-wise testing.ResultsBreed, sex, neuter status, age and body mass did not differ between groups. Sedation scores before substance administration were similar between groups (p = 0.2). Sedation scores after sedation were significantly higher in Group MB (mean 9.5 ± SD 5.5) than in group S (2.5 ± 1.8) (p < 0.001), group M (3.1 ± 2.5) (p < 0.001) and group B (3.7 ± 2.0) (p = 0.003). Sedation score difference was significantly higher in Group MB [7 (0–13)] than in Group S [0 (?1 to 4)] (p < 0.001) and Group M [0 (0–6)] (p < 0.001). HR decreased significantly in Groups M and MB compared with Group S (p < 0.05).Conclusion and clinical relevanceLow-dose medetomidine 1 μg kg?1 IV combined with butorphanol 0.1 mg kg?1 IV produced more sedation than medetomidine or butorphanol alone. HR was significantly decreased in both medetomidine groups.  相似文献   

9.

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   

10.
ObjectiveTo evaluate the dexmedetomidine‐induced reduction in organ blood flow with quantitative contrast‐enhanced ultrasound (CEUS) method and to observe the influence of MK‐467 on such reduction.Study designRandomized cross‐over study.AnimalsSix adult purpose‐bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg).MethodsContrast‐enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 μg kg?1 (DEX) and DEX + MK‐467 500 μg kg?1 (DMK) intravenously (IV). The kidney (10–15 minutes post‐treatment), spleen (25–30 minutes post‐treatment), small intestine (40–45 minutes post‐treatment) and liver (50–55 minutes post‐treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash‐in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination.ResultsAT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration.ConclusionsContrast‐enhanced ultrasound was effective in detecting DEX‐induced changes in blood flow. MK‐467 attenuated these changes.Clinical relevanceClinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK‐467 might beneficially impact the haemodynamic function of sedation with alpha‐2 adrenoceptor agonists.  相似文献   

11.

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   

12.
ObjectiveTo compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.Study designProspective, randomized cross-over study.AnimalsEight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.MethodsThe dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg?1 (MED), medetomidine 10 μg kg?1 with MK-467 250 μg kg?1 (MMK), or acepromazine 0.01 mg kg?1 with butorphanol 0.3 mg kg?1 (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2I), systemic oxygen consumption index (VO2I) and oxygen extraction (EO2) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.ResultsHR, CI, DO2I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO2, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO2I, VO2I, EO2, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB.Conclusions and clinical relevanceMK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.  相似文献   

13.
ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α2-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study designRandomized, masked crossover study.AnimalsA total of eight purpose-bred Beagle dogs aged 3 years.MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg–1) and butorphanol (100 μg kg–1) premedication with vatinoxan (500 μg kg–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg–1). Atipamezole (100 μg kg–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.  相似文献   

14.

Objective

We determined the possible effects of a peripherally acting α2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) coadministered medetomidine, butorphanol and midazolam.

Study design

Randomized, experimental, blinded crossover study.

Animals

Six healthy Beagle dogs.

Methods

Two IM treatments were administered: 1) medetomidine hydrochloride (20 μg kg–1) + butorphanol (100 μg kg–1) + midazolam (200 μg kg–1; MBM) and 2) MBM + MK-467 hydrochloride (500 μg kg–1; MBM–MK), mixed in a syringe. Heart rate was recorded at regular intervals. Sedation was assessed with visual analog scales (0–100 mm). Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry, with chiral separation of dex- and levomedetomidine. Maximum drug concentrations in plasma (Cmax) and time to Cmax (Tmax) were determined. Paired t-tests, with Bonferroni correction when appropriate, were used for comparisons between the treatments.

Results

Data from five dogs were analyzed. Heart rate was significantly higher from 20 to 90 minutes after MBM–MK. The Tmax values for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with coadministration of MK-467, from 23 ± 9 to 11 ± 6 minutes (p = 0.049) for midazolam and from 32 ± 15 to 18 ± 6 minutes for levomedetomidine (p = 0.036), respectively.

Conclusions and clinical relevance

MK-467 accelerated the absorption of IM coadministered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects.  相似文献   

15.
ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg?1); anaesthesia was induced with IV ketamine (2.2 mg kg?1) and diazepam (0.02 mg kg?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg?1 hour?1). Group MB (n = 31) received butorphanol CRI (25 μg kg?1 IV bolus then 25 μg kg?1 hour?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO2 in the normal range. Horses received lactated Ringer’s solution 5 mL kg?1 hour?1, dobutamine <1.25 μg kg?1 minute?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute?1), pH, PaO2 (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.  相似文献   

16.
ObjectiveTo establish an accurate anaesthetic dose for chemical restraint of African mole-rats using ketamine and xylazine.Study designProspective nonrandomized laboratory study.AnimalsSixteen adult Ansell’s mole-rats (Fukomys anselli) and eight giant mole-rats (F. mechowii).MethodsFukomys anselli of different ages, sexes and reproductive status were systematically anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg−1) and increasing the doses in steps of 0.5 mg kg−1 until loss of the righting reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine, starting at 0.5 mg kg−1 that was increased by 0.5 mg kg−1 in further trials. Once an effective combination was established and evaluated in F. anselli, it was also tested in F. mechowii. Heart and respiratory rates and rectal temperatures were measured during anaesthesia. anova for repeated measures and Student’s t-test were used to compare means.ResultsChemical restraint was accomplished at a dose of 6 mg kg−1 ketamine combined with 2.5 mg kg−1 xylazine. LRR lasted on average mean 56 ± SD 19 minutes (F. anselli) and 140 ± 41 minutes (F. mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 ± 15 minutes (F. anselli) and for 29 ± 2 minutes (F. mechowii), respectively. All animals recovered satisfactorily. Heart and respiratory rates were stable during anaesthesia, but rectal temperature fell significantly in F. mechowii after losing the righting reflex (LRR) from T1 (32.6 ± 0.6 °C) to T3 (30.4 ± 0.9 °C).Conclusions and Clinical relevanceAfrican mole-rats (Bathyergidae) live in closed burrow systems under particular conditions (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several physiological adaptations. Injectable anaesthetics in the dose rates used in other rodents are not appropriate for use in these subterranean species. Here, a reliable protocol for chemical restraint is provided.  相似文献   

17.
ObjectiveTo investigate physiological and sedative/immobilization effects of medetomidine or dexmedetomidine combined with ketamine in free-ranging Chinese water deer (CWD).Study designProspective clinical trial.Animals10 free-ranging adult Chinese water deer (11.0 ± 2.6 kg).MethodsAnimals were darted intramuscularly with 0.08 ± 0.004 mg kg?1 medetomidine and 3.2 ± 0.2 mg kg?1 ketamine (MK) or 0.04 ± 0.01 mg kg?1 dexmedetomidine and 2.9 ± 0.1 mg kg?1 ketamine (DMK) If the animal was still laterally recumbent after 60 minutes of immobilization, atipamezole was administered intravenously (MK: 0.4 ± 0.02 mg kg?1, DMK: 0.2 ± 0.03 mg kg?1). Heart rate (HR) respiratory rate (fR) and temperature were recorded at 5-minute intervals. Arterial blood was taken 15 and 45 minutes after initial injection. Statistical analysis was performed using Student’s t-test or anova. p < 0.05 was considered significant.ResultsAnimals became recumbent rapidly in both groups. Most had involuntary ear twitches, but there was no response to external stimuli. There were no statistical differences in mean HR (MK: 75 ± 14 beats minute?1; DMK: 85 ± 21 beats minute?1), fR (MK: 51 ± 35 breaths minute?1; DMK; 36 ± 9 breaths minute?1), temperature (MK: 38.1 ± 0.7 °C; DMK: 38.4 ± 0.5 °C), blood gas values (MK: PaO2 63 ± 6 mmHg, PaCO2 49.6 ± 2.6 mmHg, HCO3? 30.8 ± 4.5 mmol L?1; DMK: PaO2 77 ± 35 mmHg, PaCO2 45.9 ± 11.5 mmHg, HCO3? 31.0 ± 4.5 mmol L?1) and biochemical values between groups but temperature decreased in both groups. All animals needed antagonism of immobilization after 60 minutes. Recovery was quick and uneventful. There were no adverse effects after recovery.Conclusion and clinical relevanceBoth anaesthetic protocols provided satisfactory immobilisation. There was no clear preference for either protocol and both appear suitable for CWD.  相似文献   

18.
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   

19.
ObjectiveInvestigate physiological and sedative/anaesthetic effects of xylazine, medetomidine or dexmedetomidine combined with ketamine in free-ranging Bennett's wallabies.Study designProspective clinical trial.AnimalsTwenty-six adult free-ranging Bennett's wallabies.MethodsAnimals were darted intramuscularly with one of three treatments: xylazine and ketamine, 2.0 and 15.0 mg kg?1, respectively (XK): medetomidine and ketamine 0.1 and 5.0 mg kg?1 (MK) and dexmedetomidine and ketamine 0.05 and 5.0 mg kg?1 (DMK). Body weights were estimated. If the animal was still laterally recumbent after 45 minutes of anaesthesia, then an alpha-2 adrenoceptor antagonist, atipamezole, was administered (XK: 0.4 mg kg?1, MK: 5 mg kg?1, DMK: 2.5 mg kg?1). Heart rate (HR) and respiratory rate (fR) were recorded at 5-minute intervals and temperature at 10-minute intervals. Venous blood was taken 30 minutes after initial injection. Statistical analysis utilized anova. p < 0.05 was considered significant.ResultsAnimals became recumbent rapidly in all groups. XK animals had muscle twitches, responded to external stimuli, and three animals required additional dosing; this was not observed in the MK and DMK groups. HR (mean ± SD beats minute?1) in XK (81 ± 4) was significantly higher than MK (74 ± 2) and DMK (67 ± 4). There were no differences in fR, temperature, blood-gas and biochemical values between groups. More animals in MK (9/10) and DMK (5/6) needed antagonism of anaesthesia compared with XK (1/10). There were no adverse effects after anaesthesia.Conclusion and clinical relevanceCardio-respiratory effects were similar in all groups. There were fewer muscle twitches and reactions to external stimuli in MK and DMK. Duration of anaesthesia was shorter in XK; most animals in MK and DMK needed atipamezole to assist recovery. All three treatments provided satisfactory sedation/anaesthesia and are suitable for use in Bennett's wallabies.  相似文献   

20.
ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg?1 hour?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute?1, 78 ± 18 beats minute?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute?1, 78 ± 14 beats minute?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO2, PaCO2, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg?1 IV followed by a constant rate infusion of 0.5 μg kg?1 hour?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.  相似文献   

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