Combining isoflurane anesthesia with midazolam and butorphanol in rats

Abstract

Representative inhalant anesthetic agent, isoflurane is commonly used during surgery in rats. However, isoflurane mediates relatively strong respiratory depression. In human and veterinary medicine, sedatives and analgesics are co-administered to complement the anesthetic action of inhalant anesthesia. The present study aimed to establish the novel balanced anesthesia that combines midazolam and butorphanol with isoflurane (MBI) in rats. Male Sprague Dawley rats were divided into 2 groups, and administered either isoflurane monoanesthesia or isoflurane with midazolam (2.5 mg/kg, ip) and butorphanol (2.0 mg/kg, ip). The minimum alveolar concentration (MAC) in each group was evaluated. Induction and recovery times were measured in each group. Adverse reactions during induction were also recorded. In each group, vital signs were assessed for 1 h under 1.5×MAC of isoflurane. Instability of vital signs was assessed under each anesthesia by calculating coefficient of variance. Compared with isoflurane monoanesthesia, MBI anesthesia caused 32% MAC reduction (isoflurane monoanesthesia: 1.30 ± 0.09%, MBI 0.87 ± 0.08%, P<0.05). MB premedication mediated smooth sedating action with low incidence of adverse reactions such as urination and defecation. Isoflurane monoanesthsesia remarkably decreased respiratory rate and saturation O2 (SPO2). In contrast, MBI anesthesia resulted in a relatively stable respiratory rate without decreases in SPO2 during the anesthetic period. In summary, MB premedication is effective for attenuating respiratory depression induced by isoflurane, and achieving smooth induction. This anesthetic protocol serves as a novel option for appropriate anesthesia in rats.

Fig. 1.

Comparison of MACs in groups treated with isoflurane alone (I) and a combination of midazolam, butorphanol, and isoflurane (MBI). Results are represented as mean ± SD of 7 rats. *P<0.05.

Fig. 2.

Measured rectal temperature in each anesthetic group. (A): rectal temperature over time in each group. (○): isoflurane-treated group. (●): group treated with a combination of midazolam, butorphanol, and isoflurane. (B): instability in rectal temperature in each group represented as coefficient variance (CV). Results are expressed as mean ± SD in 6 rats. †Significant difference from baseline (P<0.05). N.S.: not significant.

Fig. 3.

Measured heart rate in each anesthetic group. (A): heart rate over time in each group. (○): isoflurane-treated group. (●): group treated with a combination of midazolam, butorphanol, and isoflurane. (B): instability in heart rate in each group represented as coefficient variance (CV). Results are expressed as mean ± SD in 6 rats. †Significant difference from baseline (P<0.05). N.S.: not significant.

Fig. 4.

Measured respiratory rate in each anesthetic group. (A): respiratory rate over time in each group. (○): isoflurane-treated group. (●): group treated with a combination of midazolam, butorphanol, and isoflurane. (B): instability in respiratory rate over time represented by coefficient variance (CV). Results are expressed as mean ± SD in 6 rats. *Significant difference between groups (P<0.05). †Significant difference from baseline (P<0.05).

Fig. 5.

Measured SPO₂ in each anesthetic group. (A): SPO₂ over time in each group. (○): isoflurane-treated group. (●): group treated with a combination of midazolam, butorphanol, and isoflurane. (B): instability in SPO₂ over time represented by coefficient variance (CV). Results are expressed as mean ± SD of 6 rats. *Significant difference between groups (P<0.05). †Significant difference from baseline (P<0.05).