Tsukamoto Atsushi, Konishi Yui, Kawakami Takako, Koibuchi Chiharu, Sato Reiichiro, Kanai Eiichi, Inomata Tomo
Laboratory of Laboratory Animal Science, Faculty of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuou-ku, Sagamihara, Kanagawa 252-5201, Japan.
Laboratory of Veterinary Internal Medicine 3, Faculty of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuou-ku, Sagamihara, Kanagawa 252-5201, Japan.
Exp Anim. 2017 Oct 30;66(4):397-404. doi: 10.1538/expanim.17-0037. Epub 2017 Jun 30.
In general, the anesthesia in neonates involves high risk. Although hypothermic anesthesia is recommended in rats up to the age of 7 days, neonatal anesthesia for later periods has not been standardized. The present study investigated the pharmacological properties of conventional anesthetic protocols in 10-day-old SD rats. The rats were anesthetized with four anesthetics: a combination of ketamine and xylazine (K/X); a combination of medetomidine, midazolam, and butorphanol (M/M/B); isoflurane; and sevoflurane. Anesthetic depth was scored by reflex response to noxious stimuli. Induction and recovery times were recorded. Vital signs and mortality rate were evaluated for safety assessment. All rats died after administration of K/X at a dose of 60/6 mg/kg, whereas K/X at 40/4 mg/kg resulted in insufficient anesthetic depth, indicating inappropriate for neonatal anesthesia. Although M/M/B at the adult rat dose (0.15/2/2.5 mg/kg) did not provide surgical anesthetic depth, the mouse dose (0.3/4/5 mg/kg) showed sufficient anesthetic depth with relatively stable vital signs. Isoflurane required a long induction period, and caused remarkable respiratory depression and hypothermia, resulted in a 25% mortality rate. In contrast, sevoflurane provided consistent surgical anesthetic depth with rapid induction. Although respiratory rate decrease was markedly observed, all rats survived. Among the anesthetic protocols investigated in the present study, sevoflurane and M/M/B at the mouse dose were recommended for the neonatal anesthesia. Compared with adult rats, the required dose of both anesthetics in neonates was higher, possibly associated with their lower anesthetic sensitivity.
一般来说,新生儿麻醉风险很高。虽然对于7日龄以内的大鼠推荐采用低温麻醉,但后期新生儿麻醉尚未标准化。本研究调查了10日龄SD大鼠常规麻醉方案的药理学特性。用四种麻醉剂对大鼠进行麻醉:氯胺酮和赛拉嗪的组合(K/X);美托咪定、咪达唑仑和布托啡诺的组合(M/M/B);异氟烷;以及七氟烷。通过对有害刺激的反射反应来评分麻醉深度。记录诱导和恢复时间。评估生命体征和死亡率以进行安全性评估。所有大鼠在给予60/6毫克/千克剂量的K/X后死亡,而40/4毫克/千克剂量的K/X导致麻醉深度不足,表明不适用于新生儿麻醉。虽然成体大鼠剂量(0.15/2/2.5毫克/千克)的M/M/B未达到手术麻醉深度,但小鼠剂量(0.3/4/5毫克/千克)显示出足够的麻醉深度且生命体征相对稳定。异氟烷诱导期长,会引起明显的呼吸抑制和体温过低,导致25%的死亡率。相比之下,七氟烷能提供稳定的手术麻醉深度且诱导迅速。虽然明显观察到呼吸频率下降,但所有大鼠均存活。在本研究调查的麻醉方案中,七氟烷和小鼠剂量的M/M/B推荐用于新生儿麻醉。与成年大鼠相比,新生儿对这两种麻醉剂的所需剂量更高,这可能与其较低的麻醉敏感性有关。