Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats
November 2022 by Dr Suze Bruins
An animal study (rats), investigating whether pre-treatment with dexmedetomidine (DEX) can reduce sevoflurane-induced neuronal hyperexcitation and corticosterone release at the time of exposure, as well as the long-term neurodevelopmental effects of sevoflurane (SEVO).
Rats were randomized into:
- DEX (25 mcg/kg intraperitoneal) before exposure to 2.1% SEVO for 6 hours
- Vehicle (intraperitoneal) before exposure to 2.1% SEVO for 6 hours
- DEX-only group received DEX without exposure to SEVO
- Control group received the vehicle only
Serum corticosterone levels were taken after 6 hours and the rats underwent various neurobehavioural tests over the following months. This was followed by collection of hippocampal tissue samples for in vitro studies. A subset was instrumented for EEG. Baseline recordings and recordings whilst receiving anaesthesia were made. Blood was taken on completion of the EEG recording for corticosterone levels.
Primary outcome: in vivo acute and long-term effects of SEVO and DEX.
Secondary outcome: The experimental results of the in vitro mechanistic studies.
DEX reduced SEVO-induced EEG-detectable epileptic seizure-like activity (hyperexcitation patterns) in neonatal rats, both in terms of frequency and duration (mean ± standard error of the mean, SEVO versus DEX + SEVO, 33.1 ± 5.3 vs 3.9 ± 5.3 seconds, P < 0.001).
DEX exacerbated SEVO-increased corticosterone levels in neonatal rats at the time of exposure (SEVO versus DEX + SEVO, 169.935 ± 20.995 versus 280.853 ± 40.963 ng/mL, P = 0.043).
DEX diminished, but did not fully prevent, SEVO-induced long-term neuroendocrine and behavioural abnormalities. It normalized DNA methylation changes in many (though not all) SEVO-affected hippocampal genes. It is not known whether these changes found in DNA methylation marks lead to transcriptional, translational, and functional abnormalities.
DEX alone, without SEVO anaesthesia, did not cause acute or long-term functional abnormalities.
Small animal study that suggests administering dexmedetomidine as an adjuvant, may improve the safety profile of sevoflurane in neonatal rats. However, dexmedetomidine only partially counteracted the sevoflurane-induced abnormalities.