Evaluation of t e anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole

Objectives To compare the anaesthetic effects of varying doses of medetomidine (MED) combined with ketamine (KET) in rats, and to determine the efficacy of atipamezole (ATI) in the reversal of these effects using electroencephalogram (EEG) and assessment of clinical parameters. Study design Prospective, randomized experimental trial. Animals Twenty-one male Sprague-Dawley rats weighing 300-398 g and aged 8-11 weeks old. Methods Three groups received intraperitoneal injections of MED (0.2, 0.4 or 0.8 mg kg ^-1) with KET (60 mg kg^-1) (MED-200, MED-400 and MED-800). Atipamezole, at doses five times higher than the previous dose of MED, was then administered intraperitoneally 70 minutes after MED-KET injection. The EEG band powers and spectral edge frequencies (SEFs), respiratory rates, reflex scores to toe-web clamping and behavioural changes were measured. Correlations between EEG parameters and reflex scores were also evaluated. Results The duration of surgical anaesthesia was directly proportional to the dose of MED. Lower frequency bands (δ1 to α2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (β1 to γ), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While α1 band power and SEF95 showed strong correlations with the depth of anaesthesia, their changes appeared before the measured decreases in reflex score. Recovery from anaesthesia was extended by increasing the dose of MED. Conclusions and clinical relevance Spectral EEG parameters may not accurately predict the depth of surgical anaesthesia because they had already changed during the induction of surgical anaesthesia. The ATI dose used in the present study may not be enough for complete reversal of anaesthesia induced by MED-KET.