Dexmedetomidine is a highly selective α2-adrenergic agonist. Recognition of the usefulness of α2 agonists is based on observa-tions of decreased anesthetic requirements in patients receiving chronic clonidine therapy. The effects of dexmedetomidine can be antagonized with α2-antagonist drugs. Dexmedetomidine is the active S-enantiomer of medetomidine, a highly selective α2-adrenergic agonist imidazole derivative that is used in veterinary medicine. Dexmedetomidine is water soluble and available as a parenteral formulation.
Dexmedetomidine undergoes rapid hepatic metabolism involving conjugation, N-methylation, and hydroxylation, followed by con-jugation. Metabolites are excreted in the urine and bile. Clearance is high, and the elimination half-time is short (Table 25–2). However, there is a significant increase in the context-sensitive half-time from 4 minutes after a 10-minute infusion to 250 minutes after an 8-hour infusion.
Dexmedetomidine produces its selective α2-agonist effects through activation of CNS α2 receptors. Hypnosis presumably results from stimulation of α2 receptors in the locus caeruleus, and the analge-sic effect originates at the level of the spinal cord. The sedative effect produced by dexmedetomidine has a different quality than that produced by other intravenous anesthetics in that it more completely resembles a physiologic sleep state through activation of endogenous sleep pathways. Dexmedetomidine is likely to be associated with a decrease in cerebral blood flow without signifi-cant changes in ICP and CMRO2. It has the potential to lead to the development of tolerance and dependence.
Dexmedetomidine infusion results in moderate decreases in heart rate and systemic vascular resistance and, consequently, a decrease in systemic blood pressure. A bolus injection may produce a tran-sient increase in systemic blood pressure and pronounced decrease in heart rate, an effect that is probably mediated through activa-tion of peripheral α2 adrenoceptors. Bradycardia associated with dexmedetomidine infusion may require treatment. Heart block, severe bradycardia, and asystole have been observed and may result from unopposed vagal stimulation. The response to anti-cholinergic drugs is unchanged.
The effects of dexmedetomidine on the respiratory system are a small to moderate decrease in tidal volume and very little change in the respiratory rate. The ventilatory response to carbon dioxide is unchanged. Although the respiratory effects are mild, upper airway obstruction as a result of sedation is possible. In addition, dexmedetomidine has a synergistic sedative effect when combined with other sedative-hypnotics.
Dexmedetomidine is principally used for the short-term sedation of intubated and ventilated patients in an ICU setting. In the operating room, dexmedetomidine may be used as an adjunct to general anesthesia or to provide sedation, eg, during awake fiberop-tic tracheal intubation or regional anesthesia. When administered during general anesthesia, dexmedetomidine (0.5–1 mcg/kg load-ing dose over 10–15 minutes, followed by an infusion of 0.2–0.7 mcg/kg/h) decreases the dose requirements for inhaled and injected anesthetics. Awakening and the transition to the postoperative set-ting may benefit from dexmedetomidine-produced sedative and analgesic effects without respiratory depression.