A Review of the Clinical uses of Dexmedetomidine

Dexmedetomidine is highly selective α2A adrenergic receptor agonist approved for shortterm sedation in an intensive care unit (ICU) setting or in non-intubated patients prior to and/or during surgical and other procedures. Dexmedetomidine is the dextro isomer of medetomidine with eight times greater selectivity for α2-adrenergic receptors than clonidine. This action in the central and peripheral nervous systems results in sedation and analgesia (sedoanalgesia). Dexmedetomidine is devoid of opioid and gabaergic activity and is not associated with respiratory depression resulting in cooperative and conscious (semi-arousable) sedation. The inhibition of sympathetic stress response mediated via α2 adrenergic receptor reduces heart rate and blood pressure, which promotes cardiovascular stability and protection. When given by continuous intravenous infusion it has a rapid onset and a relatively short duration of action (offset is secondary to infusion duration). Dexmedetomidine has been associated with decreased ICU costs in adult patients due to reduced time on mechanical ventilation and length of stay. The lack of respiratory depression allows for rapid extubation despite sedative therapeutic plasma concentrations. Dexmedetomidine possesses some analgesic activity; other applications include as a premedication, in the prevention of emergence delirium or agitation, and for the control of shivering. Use of dexmedetomidine is associated with reduced requirements for analgesics, sedatives and general anesthetics. There are no significant drug-drug interactions due to protein binding or metabolism. Biotransformation is almost complete to inactive metabolites. Dexmedetomidine has been reported to cause higher rates of bradycardia and hypotension, but a lower incidence of neurocognitive dysfunction including delirium. Inhibition of inflammation and activation of protective signaling pathways suggest a possible neuro protective effect. Dexmedetomidine has a very low incidence of withdrawal effects, even after prolonged use. Intranasal, buccal and oral formulations have been developed. Dexmedetomidine is not known as a substance of abuse and it is not a controlled substance.