Dexmedetomidine—an intravenously administered α₂-agonist with sedative, analgesic, sympatholytic, and anxiolytic properties—is relatively unique in its ability to preserve respiratory drive and airway reflexes. Dexmedetomidine has been approved by the U.S. Food and Drug Administration for use in two situations: (1) as a short-term (<24 h) infusion in intubated and mechanically ventilated adults in the intensive care unit and (2) in nonintubated adults before or during operations or other procedures requiring sedation. Many off-label uses have also been reported (Box 86-1).

A water-soluble imidazole compound, dexmedetomidine is the pharmacologically active dextroisomer (S-enantiomer) of medetomidine (Figure 86-1). This highly selective α₂-agonist has an eight times greater affinity for the α₂-receptor than does clonidine and has α₂:α₁ activity of 1620:1. Presynaptic α₂-adrenoceptor activation, primarily in the spinal cord, inhibits release of norepinephrine, terminating the propagation of pain signals. Postsynaptic α₂-adrenoceptor activation in the central nervous system, primarily the locus coeruleus, both inhibits sympathetic activity and modulates vigilance (Figure 86-2). Combined, these effects produce analgesia, sedation, and anxiolysis and, similar to clonidine, may decrease blood pressure and heart rate.