Dexmedetomidine and clonidine induce long-lasting activation of the respiratory rhythm generator of neonatal mice: Possible implication for critical care

Dexmedetomidine and clonidine are alpha-2 adrenoceptor agonists increasingly used in the critical care unit as sedative agents for their benzodiazepine-sparing effects and their limited depressing effect on breathing. However adverse effects on breathing have been also reported with alpha-2 adrenoceptor agonists and their central effects on the respiratory rhythm generator are poorly known. We therefore examined the effects of dexmedetomidine, clonidine, the alpha-2 adrenoceptor antagonist yohimbine and the benzodiazepine midazolam on the activity of the isolated respiratory rhythm generator of neonatal mice using medullary preparations where the respiratory rhythm generator continued to function in vitro. For the first time, we showed that 5 min bath applications of dexmedetomidine or clonidine activated the respiratory rhythm generator for periods over than 30 min. Second, we showed that the long-lasting effect of dexmedetomidine implicated receptors other than alpha-2 adrenoceptors as it persisted after their blockade with yohimbine. Third, we reported that 5 min bath applications of the benzodiazepine midazolam significantly depressed the respiratory rhythm generator, and that this depression was prevented by pre-treatment with either dexmedetomidine or clonidine. Although further experiments are still required to identify the mechanisms through which dexmedetomidine and clonidine activate the respiratory rhythm generator, our current in vitro results in neonatal mice support the use of dexmedetomidine and clonidine in the critical care unit.

► Dexmedetomidine and clonidine are commonly used alpha-2 adrenoceptor agonists.
► Whether they depress breathing in the critical care setting is under debate.
► We then examined their effects on the mouse respiratory rhythm generator in vitro.
► Both drugs facilitated its activity and prevented its depression by benzodiazepine.
► Our results support dexmedetomidine and clonidine use in the critical care setting.