Acta Anaesthesiol Scand, July 2014.
Duan X, Li Y, Zhou C, Huang L, Dong Z.


Background: Ketamine and dexmedetomidine are increasingly used in combination in pediatric patients. This study examined the hypothesis that dexmedetomidine attenuated ketamine-induced neurotoxicity.

Methods: Neonatal rats were randomly divided into four groups (n = 10, male 5, female 5). Group S + S received an equal volume of normal saline intraperitoneally and subcutaneously at an interval of 5 min. Group K + S received an intraperitoneal injection of 75 mg/kg ketamine followed by subcutaneous injection of normal saline 5 min later. Group S + D were given subcutaneously 25 μg/kg dexmedetomidine 5 min after injection of normal saline. Group K + D received a subcutaneous injection of 25 μg/kg dexmedetomidine 5 min after ketamine injection. The above drugs were given once daily for 3 days. Neuronal apoptosis in the CA1 region and the dentate gyrus of rats was examined by transferase dUTP nick end labeling (TUNEL) assays. Learning and memory abilities of 2-month old rats were examined by Morris water maze test. The results were analyzed by analysis of variance.

Results: The percentage of TUNEL-positive cells in group K + S (CA1, 49.0 ± 9.46 and dentate gyrus, 49.4 ± 5.41) was markedly higher than that in group K + D (CA1, 37.2 ± 5.54 and dentate gyrus, 35.2 ± 5.06) (F = 5.49, P < 0.05 and F = 13.51, P < 0.001, respectively). Group K + S took significantly longer time and swimming distance to find the hidden platform on the fourth and fifth training days than group K + D (P < 0.05). Moreover, group K + D spent considerably more time in the target quadrant than group K + S (P < 0.05). Dexmedetomidine alone caused a small but statistically insignificant increase in neuronal apoptosis of the CA1 region and the dentate gyrus of neonatal rats compared with normal saline.

Conclusion: In conclusion, ketamine caused neuroapoptosis and impaired brain functions in the developing rat brain which can be effectively attenuated by dexmedetomidine. Dexmedetomidine alone was not neurotoxic to the developing brain.

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