Objective

To evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI).

Study design

Prospective, randomized, masked, crossover experimental study.

Animals

A group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)].

Methods

Levomethadone 0.1 mg kg^–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05.

Results

Horses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration.

Conclusions and Clinical Relevance

A single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α₂-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.

中文翻译：

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左美沙酮对罗米非定镇静立马的镇痛作用

客观的

评估在罗米菲定恒速输注 (CRI) 期间向马注射左美沙酮静脉推注的镇痛作用。

学习规划

前瞻性、随机、掩蔽、交叉实验研究。

动物

一组八匹成年温血马（七匹阉马，一匹母马），年龄 6.6 ± 4.4 岁，体重 548 ± 52 公斤 [平均值 ± 标准偏差 (SD)]。

方法

开始使用罗米非定 CRI 后 60 分钟，向站立的马静脉注射左美沙酮0.1 mg kg ^–1或等体积的盐水（对照）。在左美沙酮给药后 150 分钟内收集血样以通过毛细管电泳定量罗米替丁和左美沙酮的血浆浓度。使用自动阈值跟踪装置连续测定伤害性撤退反射阈值 (NWRT)。定期评估镇静和心肺变量。阐述了药代动力学-药效学（PK-PD）模型。在适当的情况下，数据表示为平均值 ± SD 或中位数（四分位距，25%–75%）。对于p < 0.05 ，组间差异被认为具有统计学意义。

结果

马匹在左美沙酮给药后表现出更高的 NWRT（相对于基线，123 ± 9%与101 ± 9%，p < 0.05）。PK-PD 模型确定了左美沙酮对 NWRT 增加的贡献。效应大小因个体而异。未观察到左美沙酮给药的不良反应。在给药后的 60 分钟内，左美沙酮对镇静评分有轻微影响。

结论和临床意义

单次注射左美沙酮有可能增加马的罗米非定 CRI 期间的 NWRT，并且可以与 α _{2 -}肾上腺素受体激动剂联合给药以增强马的抗伤害感受。然而，个体差异是显着的。