General Anesthesia Induced by a Combination of Medetomidine/Vatinoxan with Ketamine and Buprenorphine-ER in C57BL/6J Mice (Mus musculus).

Medetomidine/vatinoxan (Zenalpha®) is a novel anesthetic combination used as a sedative and analgesic in dogs. Vatinoxan minimizes adverse cardiopulmonary effects associated with medetomidine administration while preserving sedation and analgesia. In this study, we evaluated the clinical safety and efficacy of 3 dosage combinations of Zenalpha with ketamine and buprenorphine extended release (ER) as compared with xylazine with ketamine and buprenorphine-ER for anesthesia of C57BL/6J mice. We hypothesized that anesthesia with 0.5 mg/kg of Zenalpha would more reliably provide a surgical anesthetic plane, lower mortality, and fewer adverse physiologic effects as compared with anesthesia with 8 mg/kg of xylazine. Ten-week-old male and female C57BL/6J mice were randomly administered 1 of 4 anesthetic cocktails subcutaneously: ketamine (80 mg/kg) and buprenorphine-ER (0.5 mg/kg) with 1) xylazine (8 mg/kg; XKB); 2) Zenalpha (0.25 mg/kg; ZKB/0.25); 3) Zenalpha (0.5 mg/kg; ZKB/0.5); or 4) Zenalpha (1.0 mg/kg; ZKB/1.0). Following drug administration, we assessed the anesthesia induction time by measuring the time to loss of righting reflex and loss of paw withdrawal reflex (PWR). Upon reaching a loss of righting reflex, physiologic parameters including heart rate, respiratory rate, oxygen saturation, indirect mean arterial blood pressure, body temperature, jaw tone, and skin color were monitored every 5 min. Thirty minutes after anesthetic drug administration (TA), atipamezole (1 mg/kg SC) was administered. Recovery time was determined through time until return of PWR, righting reflex, and ambulation. Mice were monitored for 3 d postanesthesia. Results included: 1) ZKB anesthesia caused loss of PWR in a dose-dependent manner; 2) physiologic parameters were similar between XKB and ZKB mice by TA in 100% O2; 3) ZKB groups took longer to recover and had a 20% to 30% mortality rate in the mid-to-high dosage groups. We conclude that anesthesia with 0.5 mg/kg of Zenalpha more reliably produced a surgical anesthetic plane but also led to decreased mean arterial pressure and increased mortality as compared with anesthesia with 8 mg/kg of xylazine. We recommend using Zenalpha (0.25 to 1.0 mg/kg) with 80 mg/kg ketamine and 0.5 mg/kg buprenorphine-ER to provide general anesthesia in C57BL/6 mice, along with supplemental 100% oxygen and atipamezole.

Continuous Rate Infusion of Alfaxalone during Ketamine-Xylazine Anesthesia in Rats.

Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine-xylazine-alfaxalone (KXA) anesthesia with ketamine-xylazine (KX) anesthesia in Sprague-Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO2, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO2, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.

The Physiologic Effects of Isoflurane, Sevoflurane, and Hypothermia Used for Anesthesia in Neonatal Rats (Rattus norvegicus).

Information regarding effective anesthetic regimens for neonatal rat pups is limited. Here we investigated whether isoflurane or sevoflurane anesthesia maintains physiologic parameters more consistently than does hypothermia anesthesia in neonatal rat pups. Rat pups (age, 4 d) were randomly assigned to receive isoflurane, sevoflurane, or hypothermia. Physiologic parameters monitored at 1, 5, 10, and 15 min included heart rate (HR), respiratory rate (RR), and oxygen saturation (%SpO2). Other parameters evaluated were loss and return of righting reflex, paw withdrawal reflex, and maternal acceptance. Corticosterone and glucose were sampled at 20 min and 24 h after anesthesia induction. Once a surgical plane of anesthesia was achieved, a skin incision was made on the right lateral thigh. After the procedure, all pups were accepted and cared for by their dam. Isoflurane- and sevoflurane-treated pups maintained higher HR, RR, %SpO2, and glucose levels than did hypothermia-treated pups. For both the isoflurane and sevoflurane groups, HR and RR were significantly lower at 10 and 15 min after anesthesia than at 1 min. Compared with hypothermia, isoflurane and sevoflurane anesthesia provided shorter times to loss of and return of the righting reflex. Although corticosterone did not differ among the groups, glucose levels were higher at 20 min after anesthesia induction than at 24 h in all anesthetic groups. We conclude that both isoflurane and sevoflurane anesthesia maintain physiologic parameters (HR, RR, %SpO2) more consistently than does hypothermia anesthesia in 4-d-old rat pups.