Anaesthesia and analgesia for surgery in rabbits and rats : a comparison of the effects of different compounds

Abstract

Studies of anaesthesia and analgesia in rats and rabbit were undertaken with the aim to improve anaesthesia techniques, for better animal welfare and research quality.

Induction of anaesthesia with the volatile halogenated agents isoflurane, sevoflurane and desflurane was compared in the New Zealand White rabbit. All agents caused struggling, breath holding and reflex bradycardia, desflurane having the least detrimental effects. Hypoxia was prevented by pre-oxygenation, and no cardiac arrhythmias were seen. Still, induction of anaesthesia in rabbits cannot be recommended with any of these agents.

Injection anaesthesia with ketamine (cyclohexamine)/medetomidine (alpha-2-adrenergic agonist) and the effect of adding the opioid butorphanol, were evaluated in the New Zealand White rabbit. Additionally, effects after subcutaneous and intramuscular administration of ketamine/medetomidine were compared. In a first study, a dose of 15/0.25 mg/kg of ketamine/medetomidine was found effective in producing surgical anaesthesia for 59 ± 18 min, but failed to produce surgical anaesthesia in some animals in a following study, possibly due to different stress levels at the time of induction. The anaesthetic effects did not differ between the administration routes. Subcutaneous injection was easier to perform and seemed less painful. Pronounced hypoxia developed during anaesthesia (PaO2 4.8 ± 0.6 kPa, mean ± SD), indicating a need for oxygen supplementation. Blind tracheal intubation was easy to perform during anaesthesia. Addition of butorphanol increased duration of anaesthesia.

In Wistar rats, anaesthesia with ketamine/medetomidine, repeated six times with weekly intervals, and the effects of pre-medication with the opioid buprenorphine, were evaluated. Buprenorphine caused an increase in duration of anaesthesia as well as greater respiratory depression, and was associated with increased lethality. Repeated anaesthesia without buprenorphine was found safe and led to an increase in sleep times with successive anaesthetics.

The combination sufentanil (opioid)/medetomidine was also evaluated in Wistar rats. Anaesthesia was more efficiently produced after subcutaneous than after intraperitoneal administration, and a sc dose of 40/150 (mu)g/kg of sufentanil/medetomidine produced surgical anaesthesia for 101 ± 49 min. Anaesthesia resulted in very low oxygen saturation levels (40 ± 20 %). Despite this, all animals recovered uneventfully. Oxygen supplementation is strongly recommended with this combination. Anaesthesia was reversed within 7 min by administration of 0.2/0.5 mg/kg of butorphanol (mixed (mu)-opioid agonist/antagonist)/atipamezole (alpha-adrenergic antagonist).

Postoperative recovery and behavior were compared in Sprague-Dawley rats after abdominal surgery under isoflurane or ketamine/medetomidine anaesthesia, and the effect of perioperative treatment with the NSAID analgesic carprofen studied. Surprisingly, rats recovered body weight faster and showed less pain-related behavior when surgery was performed under isoflurane anaesthesia, and locomotion was also less reduced. The effects on body weight after surgery under ketamine/medetomidine anaesthesia were not just seen in the immediate postoperative period, but also for several days after. Perioperative treatment with carprofen reduced the detrimental effects in both isoflurane and ketamine/medetomidine anaesthetized animals. The results show that the choice of anaesthesia may be just as important as the use of analgesic treatment for improved recovery and reduction of pain after surgery.