Alfaxalone as a Total Intravenous Anesthesia Protocol in New Zealand White Rabbits (Oryctolagus cuniculus) Improves Cardiovascular Stability Compared to Isoflurane
Alfaxalone has been studied for anesthetic induction of rabbits with rapid onset and a short duration of action; however, it has been minimally evaluated as an option for anesthetic maintenance. This study compared alfaxalone-based total intravenous anesthesia maintenance protocols against inhaled isoflurane, the current standard for anesthetic maintenance in rabbits. Twenty-four male New Zealand White rabbits were assigned to 1 of 3 treatment groups: isoflurane alone, alfaxalone with buprenorphine, or alfaxalone with midazolam. All rabbits were premedicated with buprenorphine HCl (0.02 mg/kg SC) and induced with alfaxalone (6 mg/kg IM). Following intubation and with supplementation of 100% O2, rabbits were maintained for 1 h on either isoflurane (2.5%) or alfaxalone continuous rate infusion (CRI) (0.2 mg/kg/min). For rabbits on the alfaxalone CRI, boluses of buprenorphine HCl (0.01 mg/kg IV or SC) or midazolam (0.1 to 0.3 mg/kg SC) were given upon induction or adjunctively as needed dependent on positive tail-pinch responses that were conducted at timepoints t0, t15, t30, t45, and t60. Heart rate, invasive blood pressure, respiratory rate, end-tidal CO2, percent O2 saturation, and temperature were recorded every 5 min. Surgical plane of anesthesia was characterized by lack of positive response to a tail clamp and was reached in all anesthetic groups. Results showed significant reduction in heart rate of the alfaxalone groups while there was no significant difference in mean arterial pressure compared with the isoflurane groups. However, respiratory rate in the alfaxalone groups was decreased with associated increases in end-tidal CO2 levels. There were no significant differences noted between alfaxalone treatment groups. The results confirmed that CRI alfaxalone (total intravenous anesthesia) should be considered as a potential anesthetic alternative to isoflurane anesthesia in rabbits, although special attention to respiratory monitoring and management is warranted.
Anesthetic monitoring and evaluation timeline. During the preinduction phase, all rabbits regardless of anesthetic group received premedication with buprenorphine (0.02 mg/kg SC) and induction with alfaxalone (6 mg/kg IM) to allow for endoscopic-guided endotracheal intubation and instrumentation. After intubation, all rabbits were started on 100% supplemental O2. Rabbits in the isoflurane group were kept at 1.5% isoflurane until t0 when isoflurane was turned up to 2.5% and remained for the entire 60-min anesthetic period. For the alfaxalone anesthetic groups, rabbits were started on the alfaxalone CRI at 0.2 mg/kg/min IV 5 min after induction to ease instrumentation. Rabbits in the midazolam group received an adjunctive dose of midazolam (0.1 to 0.3 mg/kg SC) at t0 and adjunctively as needed while rabbits in the buprenorphine group received adjunctive doses at 0.01 mg/kg IV or SC as needed.
Throughout the 60-min period, the heart rate of rabbits undergoing isoflurane maintenance anesthesia was significantly elevated compared with rabbits receiving alfaxalone CRI for maintenance anesthesia, and anesthetic group, but not time, was a significant factor. Heart rate was measured via ECG every 5 min during the 60-min period. Data are shown as mean ± SEM, and analysis using 2-way ANOVA with repeated measures followed by Bonferroni multiple comparison was performed for all anesthetic groups. *, P 0.05 (indicating that anesthetic group was a significant factor).
Mean arterial pressures of all 3 anesthetic maintenance groups were not significantly different at any timepoint, and neither anesthetic group nor time were significant factors. MAP was measured every 5 min via the auricular artery during the 60-min period. Overall, rabbits in the 2 alfaxalone groups had clinically improved MAP compared with those of the isoflurane group during the 60-min period. Data are shown as mean ± SEM, and analysis using 2-way ANOVA with repeated measures followed by Bonferroni multiple comparison was performed for all anesthetic groups. Significance was set at P 0.05.
Rabbits in the alfaxalone group had significantly decreased respiratory rates compared with those in the isoflurane group, and anesthetic group and time were significant factors. Respiratory rate was measured via capnograph every 5 min during the 60-min period. Clinically, rabbits in the alfaxalone groups developed moderate to severe apnea after the start of the alfaxalone CRI while the rabbits in the isoflurane group maintained normal spontaneous ventilation throughout. Data are shown as mean ± SEM, and analysis using 2-way ANOVA with repeated measures followed by Bonferroni multiple comparison was performed for all anesthetic groups. *, P 0.05 (indicating that anesthetic group and time were significant factors).
Rabbits in the alfaxalone group had significantly elevated ETCO2 levels compared with those in the isoflurane group, and anesthetic group, but not time, was a significant factor. ETCO2 levels were measured via capnograph every 5 min during the 60-min period. At t15, t45, and t60, ETCO2 levels of the 2 alfaxalone CRI groups were significantly elevated compared with the levels recorded for isoflurane-maintained rabbits. At t30, ETCO2 levels of the alfaxalone and midazolam group only were significantly elevated compared with those of the isoflurane rabbits. Data are shown as mean ± SEM, and analysis using 2-way ANOVA with repeated measures followed by Bonferroni multiple comparison was performed for all anesthetic groups. *, P 0.05 (indicating that anesthetic group was a significant factor).
Contributor Notes