Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23, Towada, Aomori 034-8628, Japan.
Exp Anim. 2024 May 3;73(2):223-232. doi: 10.1538/expanim.23-0158. Epub 2024 Jan 20.
Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. "Balanced anesthesia" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.
在生物医学研究中，对实验动物进行伦理治疗离不开恰当的麻醉管理。因此，选择有效的麻醉方案对于实验的设计和成功至关重要。因此，不断开发和改进麻醉剂对于提高研究结果和提升动物福利是必要的。“平衡麻醉”涉及使用多种药物来优化疗效，同时将副作用降至最低。在日本，使用咪达唑仑、咪达唑仑、布托啡诺的 MMB 和使用甲磺酸达比加群酯、咪达唑仑、布托啡诺的 MAB 较为流行。然而，咪达唑仑的缺点，包括其恢复时间延长和 MAB 的安全边际狭窄，促使人们研究合适的替代品。本研究用具有超短半衰期的瑞马唑仑（RMZ）替代 MMB 组合中的咪达唑仑。由此产生的组合，称为 MRB，与 MAB 相比，提供了更宽的安全边际，同时在小鼠中维持与 MMB 相当的麻醉深度。值得注意的是，与 MMB 相比，MRB 在给予拮抗剂后恢复评分始终更好。此外，MRB 没有观察到 MMB 观察到的再镇静现象。RMZ 的快速代谢使可靠的麻醉诱导成为可能，避免了与 MAB 相关的并发症。总的来说，MRB 在提供延长的手术麻醉和迅速的拮抗剂恢复方面表现出色。这些结果突出了 RMZ 在更广泛的动物研究应用中的潜力。
