Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses

ObjectiveTo compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses.Study designProspective ‘blinded’ controlled trial using block randomization.AnimalsForty healthy Freiberger stallions.MethodsThe horses received either intravenous (IV) romifidine (loading dose: 80 μg kg^?1; infusion: 30 μg kg^?1 hour^?1) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 μg kg^?1; infusion: 29 μg kg^?1 hour^?1, and butorphanol loading: 18 μg kg^?1; infusion: 25 μg kg^?1 hour^?1) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 μg kg^?1) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant.ResultsSedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9–9.0 cm, RB: 8.8, 4.7–10.0 cm, and by the dentist R: 6.6, 3.0–8.2 cm, RB: 7.9, 6.6–8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation.Conclusions and clinical relevanceThe described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.     

Effects of intramuscular alfaxalone alone or in combination with diazepam in swine

ObjectiveTo describe the use of intramuscular (IM) premedication with alfaxalone alone or in combination with diazepam in pigs.Study designRandomised‐controlled trial.AnimalsTwelve healthy 2 month‐old Landrace x Large White pigs weighing 21.3 ± 2.4 kg.MethodsAnimals were distributed randomly into two groups: group A (n = 6) 5 mg kg^?1 of IM alfaxalone; and group AD (n = 6) 5 mg kg^?1 of IM alfaxalone + 0.5 mg kg^?1 of IM diazepam mixed in the same syringe. The total volume of injectate was standardized at 14 mL by dilution in 0.9% sodium chloride. Pain on injection, the degree of sedation and the quality of and time to induction of recumbency were evaluated. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Pigs were then moved to another room for subsequent anaesthesia.ResultsTwo animals of group A and one of group AD showed slight pain on drug injection. Time to lateral recumbency (in seconds) was shorter in group AD (mean 203 ± SD 45 range 140–260) than group A (302 ± 75, range 220–420; p < 0.05). In group AD sedation was deeper, and on recumbency there was better muscle relaxation. When moved for anaesthesia, two pigs in Group A showed slight resistance but did not vocalize. There were no differences in physiologic measurements between groups, although in both groups, respiratory rate was significantly lower at ten compared with five minutes post drug injection. There was no apneoa.Conclusions and clinical relevanceIM administration of alfaxalone combined with diazepam resulted in a rapid onset of recumbency and deep sedation, with minimal side effects. The combination might be useful for premedication, but volume of injectate will limit its use to small pigs.     

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.