Dexmedetomidine (Precedex; Abbott Labs, Abbott Park, IL, USA) is a relatively selective α₂-adrenergic receptor agonist (eight times more specific for the α₂-adrenoreceptor compared to clonidine). Compared to other α₂-adrenergic agonists such as clonidine, dexmedetomidine has a shorter half-life (2 hours for intravenous dexmedetomidine versus 8 to 12 hours for peroral clonidine).

Dexmedetomidine stimulates a₂-adrenoreceptors in the locus ceruleus of the brainstem to provide sedation. It also provides analgesia by stimulating a₂-adrenoreceptor in the central and peripheral nervous systems. Dexmedetomidine causes sympatholysis via central and peripheral mechanisms. Following intravenous (IV) administration, dexmedetomidine undergoes rapid redistribution, with a distribution half-life of 6 minutes and an elimination half-life of 2 hours. Dexmedetomidine exhibits linear kinetics in the dosing range of 0.2 to 0.7 mcg/kg/h when administered through IV infusion for 24 hours. Dexmedetomidine is 94% protein-bound and undergoes nearly complete biotransformation in the liver to inactive metabolites that are excreted in the urine.

During a continuous infusion within its therapeutic level, dexmedetomidine provides unique sedation (patients appear to be asleep but are readily aroused), analgesic-sparing effect, and minimal depression of respiratory function. Dexmedetomidine has no pharmacokinetic or cytochrome P450 enzyme drug-drug interactions.

Hypotension, hypertension, nausea, bradycardia, fever, and vomiting are most frequently observed adverse events associated with dexmedetomidine. The net effect of α₂-adrenergic agonists, exerted via central and spinal receptors, is sympatholytic (or “provagal”). Therefore, caution should be exercised in patients with pre-existing severe bradycardia disorders or severe ventricular dysfunction, in whom sympathetic tone is critical for maintaining hemodynamic balance. Clinical events of bradycardia and sinus arrest have been associated with dexmedetomidine administration in young, healthy volunteers with high vagal tone or with different routes of administration including rapid IV/bolus administration (www.fda.gov/cder/foi/label/1999/210381bl.pdf). Transient hypertension has also been observed, primarily during the loading infusion, associated with initial peripheral vasoconstriction effects of dexmedetomidine prior to its central nervous system (CNS)-mediated vasodilatory effect.

Recent clinical studies, however, demonstrated more reliable control of heart rate and blood pressure in patients undergoing surgery with appropriate doses of dexmedetomidine. Dose reduction should be considered in patients with impaired liver and renal function. Dexmedetomidine is contraindicated in patients with a known hypersensitivity to the drug, which has not been reported so far.

In 1999, dexmedetomidine was approved by the U.S. Food and Drug Administration (FDA) for sedation of adult patients who are intubated and mechanically ventilated in the intensive care setting. Dexmedetomidine should be administered by continuous infusion not to exceed 24 hours.

Dexmedetomidine is supplied in 2-mL vials each containing 100 mcg of drug/mL (200 mcg total) and should be diluted with 48 mL of sterile water or 0.9% sodium chloride to a final concentration of 4 mcg/mL. Dexmedetomidine is recommended to be administered as a loading dose of 1 mcg/kg over 10 to 20 minutes, followed by a maintenance infusion of 0.2 to 0.7 mcg/kg/h, titrated to the desired sedation scale.