PDF(Pubmed)
Abstract：
The effects of commonly used injectable combinations of anesthetics such as ketamine and xylazine, with or without acepromazine, vary widely across individuals, have a shallow-dose response curve, and do not provide long-term analgesia. These drawbacks indicate the importance of continuing efforts to develop safe and effective injectable anesthetic combinations for mice. In this study, a series of experiments was designed to validate the use of dexmedetomidine and midazolam to provide chemical restraint for nonpainful procedures and the addition of buprenorphine or extended-release buprenorphine to reliably provide a surgical plane of anesthesia in C57BL/6J mice. Loss of consciousness was defined as the loss of the righting reflex (LORR); a surgical plane of anesthesia was defined as the LORR and loss of pedal withdrawal after application of a 300 g noxious stimulus to a hind paw. The combination of intraperitoneal 0.25 mg/kg dexmedetomidine and 6 mg/kg midazolam produced LORR, sufficient for nonpainful or noninvasive procedures, without achieving a surgical plane in 19 of 20 mice tested. With the addition of subcutaneous 0.1 mg/kg buprenorphine or 1 mg/kg buprenorphine-ER, 29 of 30 mice achieved a surgical plane of anesthesia. The safety and efficacy of the regimen was then tested by successfully performing a laparotomy in 6 mice. No deaths occurred in any trial, and, when administered 1 mg/kg atipamezole IP, all mice recovered their righting reflex within 11 min. The anesthetic regimen developed in this study is safe, is reversible, and includes analgesics that previous studies have shown provide analgesia beyond the immediate postsurgical period. Buprenorphine-ER can be safely substituted for buprenorphine for longer-lasting analgesia.
摘要：
常用的麻醉药如氯胺酮和赛拉嗪的注射组合的效果，有或没有乙酰丙嗪，不同的个体差异很大，有一个浅的剂量反应曲线，并且不提供长期镇痛。这些缺点表明继续努力开发用于小鼠的安全和有效的可注射麻醉剂组合的重要性。在这项研究中,设计了一系列实验,以验证在C57BL/6J小鼠中使用右美托咪定和咪达唑仑为非疼痛性手术提供化学约束,以及添加丁丙诺啡或缓释丁丙诺啡可靠地提供手术麻醉平面.意识丧失被定义为正确反射（LORR）的丧失；对后爪施加300g有害刺激后，手术麻醉平面被定义为LORR和踏板退出的丧失。腹腔注射0.25mg/kg右美托咪定和6mg/kg咪达唑仑联合产生LORR，足以进行非疼痛或非侵入性手术，在测试的20只小鼠中，有19只没有达到手术平面。皮下添加0.1mg/kg丁丙诺啡或1mg/kg丁丙诺啡-ER，30只小鼠中的29只取得了手术平面的麻醉。然后通过在6只小鼠中成功进行剖腹手术来测试该方案的安全性和功效。在任何试验中都没有死亡,and,当IP给药1mg/kg阿替美唑时，所有小鼠在11分钟内恢复了正正反射。这项研究中开发的麻醉方案是安全的，是可逆的，并包括先前研究显示可在术后即刻提供镇痛的镇痛药。丁丙诺啡-ER可以安全地替代丁丙诺啡，以实现更持久的镇痛。
