Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole.
OBJECTIVE
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.


METHODS
Prospective, randomized experimental trial.


METHODS
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 (delta 1 to alpha2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (beta1 to gamma), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While alpha1 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
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.
Jang
Hwan S
HS
Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu, Korea.
Choi
Hyo S
HS
Lee
Sung Hee
SH
Jang
Kwang H
KH
Lee
Maan-Gee
MG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000768:Anesthesia, General / Q000662:veterinary*; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D000778:Anesthetics, Dissociative; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C050701:atipamezole; D007649:Ketamine; D020926:Medetomidine