Pakkanen Soile Ae, Raekallio Marja R, Mykkänen Anna K, Salla Kati M, de Vries Annemarie, Vuorilehto Lauri, Scheinin Mika, Vainio Outi M
Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Animal Health Trust, Newmarket, Suffolk, UK.
Vet Anaesth Analg. 2015 Sep;42(5):527-36. doi: 10.1111/vaa.12238. Epub 2014 Dec 22.
To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.
Experimental, crossover study with a 14 day wash-out period.
Seven healthy horses.
The 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 (Pa O2 /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.
The 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 Pa O2 /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.
MK-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.
研究MK - 467作为异氟烷麻醉马匹术前用药的一部分的效果。
实验性交叉研究，洗脱期为14天。
7匹健康马匹。
马匹术前用药分别单独给予右美托咪定（20μg kg⁻¹静脉注射）和布托啡诺（20μg kg⁻¹静脉注射）（DET），或加用MK - 467（200μg kg⁻¹静脉注射；DET + MK）。静脉注射氯胺酮（2.2mg kg⁻¹）和咪达唑仑（0.06mg kg⁻¹）诱导麻醉，并用异氟烷维持。记录心率（HR）、平均动脉压（MAP）、呼气末异氟烷浓度、呼气末二氧化碳分压、中心静脉压、吸入氧分数（FiO₂）和心输出量。采集血样进行血气分析并测定血浆药物浓度。计算心脏指数（CI）、全身血管阻力（SVR）、动脉血氧分压与吸入氧的比值（Pa O₂/FiO₂）和组织氧输送（DO₂）。对HR、CI、MAP、SVR乳酸和血气变量应用重复测量方差分析。采用Student's t检验对药物浓度、诱导时间和多巴酚丁胺给药量进行两两比较。显著性设定为p < 0.05。
DET + MK组诱导时间更短，检测到MAP降低，给予更多多巴酚丁胺，HR和CI更高，而DET组SVR更高。DET + MK组动脉血氧分压和Pa O₂/FiO₂（诱导后40分钟）、DO₂和静脉血氧分压（诱导后40和60分钟）更高。接受MK - 467的组血浆右美托咪定浓度降低。DET + MK组后，布托啡诺血浆浓度 - 时间曲线下面积更小。
MK - 467可增强异氟烷麻醉前用右美托咪定镇静马匹的心脏功能和组织氧输送。这一发现可提高围手术期患者安全性。需要研究MK - 467的剂量以尽量减少其对MAP的影响。
