Dexmedetomidine: a novel sedative-analgesic agent

Abstract

Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.

Figure 1

Physiology of the α₂-adrenoceptor agonists receptor. Reprinted from dexmedetomidine.com with permission of DocMD.com.

Figure 2

Responses that can be mediated by α₂-adrenergic receptors. Reprinted from Kamibayashi T, Maze M. Clinical uses of alpha 2-adrenergic agonists. Anesthesiology 2000;93:1345–1349 with the permission of the American Society of Anesthesiologists.

Figure 3

Cardiorespiratory variables before, during, and after infusion of dexmedetomidine of 0.2 (▴) or 0.6 (○) μg·kg^-1/hr¹ or placebo (□). SpO₂ indicates arterial oxyhemoglobin saturation; ETCO₂, end-tidal carbon dioxide. Adapted with permission from Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699–705.

Figure 4

Side effects of dexmedetomidine. Adapted from Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59:263–268.

Figure 5

Potential role of dexmedetomidine for sedation in the intensive care unit. Reprinted from dexmedetomidine.com with permission of DocMD.com.