Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits

Abstract

Medetomidine (MED), midazolam (MID), and butorphanol (BUT) mixed anesthetic (MMB) has been used in laboratory animals since ketamine (KET) was designated as a narcotic in Japan in 2007. We previously reported that MMB produced anesthetic effects in mice and rats. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED produced a quick recovery from anesthesia. Anesthetics have various anesthetic effects among different animal species. However, there is little information regarding its effects in rabbits. In the present study, we examined anesthetic effects of MMB compared to KET and xylazine mixed anesthetic (KX). We examined the antagonistic effects of ATI by intramuscular (IM) or intravenous (IV) injection in rabbits. We used the anesthetic score to measure surgical anesthetic duration and recovery time from anesthesia. During the experiments, we measured heart rate, respiratory rate, O₂-saturation, and blood pressure. We found there were no significant differences in anesthetic duration and recovery time between MMB and KX. There were no significant differences in heart rate after administration of MMB or KX. Systolic blood pressure at 10 min after administration of MMB was higher than that of KX. The antagonistic effect of ATI by IV injection worked faster than that by IM injection. Overall, MMB is a useful drug that can induce similar anesthetic effects to KX and has an antagonist of ATI that makes rabbits quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals, especially rabbits.

Keywords: anesthetic mixture; antagonist; blood pressure; ketamine; rabbits.

Fig. 1.

Time courses of heart rate (A), respiratory rate (B), and O₂-saturation (C) of the medetomidine, midazolam, and butorphanol mixed anesthetic (MMB) and the Non-anesthetized groups. Differences between two groups were analyzed using unpaired Student’s t-test. A P value of less than 0.05 was considered statistically significant. *P<0.05 compared with the Non-anesthetized group.

Fig. 2.

Time courses of the anesthetic score of the medetomidine, midazolam, and butorphanol mixed anesthetic (MMB) and the ketamine and xylazine mixed anesthetic (KX) groups. Data are presented as means ± SD. Differences between two groups were analyzed using unpaired Student’s t-test. A P value of less than 0.05 was considered statistically significant. *P<0.05 compared with the KX group.

Fig. 3.

Time courses of systolic blood pressure (A) and diastolic blood pressure (B) of the medetomidine, midazolam, and butorphanol mixed anesthetic (MMB) and the ketamine and xylazine mixed anesthetic (KX) groups. Data are presented as means ± SD. Differences between two groups were analyzed using unpaired Student’s t-test. A P value of less than 0.05 was considered statistically significant. *P<0.05 compared with the KX group.

Fig. 4.

Time courses of heart rate of the medetomidine, midazolam, and butorphanol mixed anesthetic (MMB) and the ketamine and xylazine mixed anesthetic (KX) groups. Data are presented as means ± SD. Differences between two groups were analyzed using unpaired Student’s t-test. A P value of less than 0.05 was considered statistically significant. There were no significant differences between two groups.

Fig. 5.

Time courses of the anesthetic score of the atipamezole (ATI)-intramuscular (IM) and the ATI-intravenous (IV) groups. Data are presented as means ± SD. Differences between two groups were analyzed using unpaired Student’s t-test. A P value of less than 0.05 was considered statistically significant. *P<0.05 compared with the ATI-IM group.