Plasma drug concentrations and clinical effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in horses sedated with detomidine

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 (AUC_sed) 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. AUC_sed 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.     

Effect of MK‐467 on organ blood flow parameters detected by contrast‐enhanced ultrasound in dogs treated with dexmedetomidine

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.     

The sedative effects of low-dose medetomidine and butorphanol alone and in combination intravenously in dogs

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.     

Antinociceptive, sedative and cardiopulmonary effects of subarachnoid and epidural xylazine-lidocaine in xylazine-sedated calves

ObjectiveTo evaluate the antinociceptive, sedative and cardiopulmonary effects of subarachnoid and epidural administration of xylazine-lidocaine in xylazine-sedated calves.Study designProspective, crossover study.AnimalsSix clinically healthy Holstein calves.MaterialsThe calves were allocated randomly to receive two treatments, subarachnoid or epidural xylazine (0.025 mg kg^?1)–lidocaine (0.1 mg kg^?1) diluted to a total volume of 5 mL with physiological saline. Prior to either epidural or subarachnoid injection, sedation was induced in all calves by intravenous administration of 0.1 mg kg^?1 xylazine. The quality and duration of antinociception and sedation were monitored. Areas of the cranial abdomen, umbilicus, and caudal abdomen were evaluated for antinociception using pinprick tests with a scoring system of 0–3 (0, none; 1, mild; 2, moderate; 3, complete). Sedation was assessed by using a 4-point scale (0, none; 1, mild; 2, moderate; 3, deep). The following cardiopulmonary variables were monitored: heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), blood pH, arterial partial pressure of oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂), bicarbonate (HCO₃), base excess (BE), and oxygen saturation (SaO₂).ResultsXylazine sedation and subarachnoid xylazine-lidocaine resulted in significantly higher nociceptive block than the epidural technique. Moreover, subarachnoid xylazine-lidocaine induced a significantly longer duration of complete antinociception (median [IQR]) in the cranial abdomen (15.0 [15.0–30.0] versus 7.5 [1.3–10.0] minutes; p < 0.05) and umbilicus (45.0 [32.5–57.5] versus 10.0 [6.3–17.5] minutes; p < 0.05) compared with epidural xylazine-lidocaine. There was moderate sedation with both techniques. In both treatments, blood pH, MAP and PaO₂ decreased significantly, and PaCO₂ increased significantly during anaesthesia. No change was evident in HR, f_R, HCO_3, BE, or SaO₂.Conclusion and clinical relevanceThe subarachnoid injection provided better quality and longer duration of antinociception than epidural administration of the same doses of xylazine-lidocaine in xylazine-sedated calves, while cardiopulmonary depressant effects were observed with both regimens.     

左旋芳樟醇及其两种复方精油的催眠镇静作用

探讨左旋芳樟醇及其两种复方精油(1号复方精油配方:左旋芳樟醇∶薰衣草精油∶依兰依兰油∶柏木油=1∶2∶4∶3,2号复方精油配方:左旋芳樟醇∶薰衣草精油∶依兰依兰油∶柏木油=5∶3∶1∶1)对小鼠的催眠镇静作用,研究精油对小鼠自主活动、阈上剂量戊巴比妥钠致小鼠睡眠潜伏期和睡眠时间、阈下剂量戊巴比妥钠致小鼠睡眠只数的影响.结果表明:3种精油对小鼠均有明显的催眠镇静作用,其中以浓度为10-3的2号复方精油的效果最佳;在小鼠自主活动能力测试中,2号复方精油组小鼠的总路程与对照组的差异极显著(P0.01),休息时间、活动时间、活跃度、中间区域时间和中央区域路程与对照组的差异显著(P0.05);与对照组相比较,2号复方精油极显著缩短小鼠睡眠潜伏期(P0.01),从(18.47±2.04)s缩短到(14.13±1.73)s,极显著延长小鼠睡眠时间(P0.01),从(27.01±5.84)s延长到(40.41±8.36)s,增加小鼠睡眠只数(P0.01),从1只增加到7只.可见,左旋芳樟醇及其两种复方精油具有明显的催眠镇静作用,以2号复方精油的效果最佳.     

Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses

ObjectiveTo elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations.Study designBlinded randomized experimental study.AnimalsTen adult research horses.MethodsPart I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg^?1) with butorphanol (XB: 18 μg kg^?1) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg^?1 hour^?1) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg^?1) whenever HHAG >50%. The dose of xylazine (mg kg^?1 hour^?1) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg^?1 hour^?1) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups.ConclusionXylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses.Clinical relevanceData were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.     

Immobilization of Norwegian reindeer (Rangifer tarandus tarandus) and Svalbard Reindeer (R. t. platyrhynchus) with medetomidine and medetomidine-ketamine and reversal of immobilization with atipamezole

The sedative action of medetomidine (-ketamine) was studied in 12 captive Norwegian semidomesticated reindeer (NR), including 4 newborn calves, and in 7 free-living Svalbard reindeer (SR). Medetomidine, with or without ketamine, caused effective, reliable immobilization in NR. Doses of 50-200 micrograms/kg medetomidine alone or 30-125 micrograms/kg medetomidine combined with greater than or equal to 300 micrograms/kg ketamine induced complete immobilization, good muscle relaxation and persistent, deep sedation with little respiratory depression in NR; SR required higher doses. Atipamezole successfully antagonized medetomidine (-ketamine) resulting in rapid and persistent reversal of immobilization in all cases (NR and SR). Both medetomidine and atipamezole had wide safety margins and no conspicuous lasting side effects after reversal.     

Effects of propofol-induced sedation on intradermal test reactions in dogs with atopic dermatitis

We compared the effect of propofol and saline control on intradermal test reactions in dogs with atopic dermatitis undergoing outpatient intradermal testing (IDT). Nineteen dogs were used in this clinical study. Patients were randomly allocated to receive either intravenous (IV) propofol or IV 0.9% saline, and IDT was performed on the right or left (randomized) lateral thorax. One investigator, unaware of the treatments, interpreted all IDT results. Injection sites were analysed using a subjective and objective method. A value of P or= 1+ on all dogs, significantly more positive sites were apparent during propofol sedation than during saline administration. In addition, the greater number of individual dogs experiencing more positive reactions >or= 1+ during propofol sedation was significant. When subjectively analysing reactions >or= 2+, the greater number of positive reactions and the greater number of dogs with more positive reactions observed during propofol treatment was not significantly different from the saline control. When analysed objectively, the greater number of positive reactions observed during propofol sedation was not significant. A greater number of dogs had higher subjective scores and larger objective measurements during propofol sedation compared with saline administration. In summary, propofol sedation was associated with an overall greater number of positive IDT reactions compared with the saline control. Although not always significant, this difference should be considered when choosing propofol for skin testing dogs with atopic dermatitis.     

Potential benefit of clove oil sedation on animal welfare during salmon smolt, Salmo salar L. transport and transfer to sea

The purpose of this study was to determine the effect of clove oil (4.0 mg L⁻¹) sedation, compared with non-sedation, on the primary (plasma cortisol), secondary (osmoregulation) and tertiary (mortality) stress responses in Atlantic salmon smolts during transport and transfer to sea. Clove oil sedation during on- and off-loading sufficiently reduced the primary stress response to lower mortality (2.1%) during transfer to sea compared with unsedated fish, which experienced a mortality rate above 12.2%. The unsedated fish experienced an acute mortality that stabilized only 6 days after the transport. None of the secondary stress responses measured in this experiment could contribute towards explaining this phenomenon, with the possible exception of plasma magnesium (Mg²⁺). Plasma Mg²⁺ differed between the groups; while plasma Mg²⁺ in the clove oil sedated group returned to pre-stress levels 72 h after transport, the unsedated group showed no such recovery even 1 week after transport, which may indicate a disturbance in the hydromineral balance, and provides a plausible explanation for the delayed mortality in this group. Eugenol-based anaesthetics appear to be promising as a stress-reducing sedative for Atlantic salmon smolts, and, if used properly, this chemical could improve animal welfare and survivability during and after common aquaculture-related incidents.