Anstesiologia

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CURRENT ROLE OF DEXMEDETOMIDINE IN CLINICAL ANESTHESIA AND INTENSIVE CARE
 
   Abstract |   | |

Dexmedetomidine is a new generation highly selective α 2-adrenergic receptor (α 2-AR) agonist that is associated with sedative and analgesic sparing effects, reduced delirium and agitation, perioperative sympatholysis, cardiovascular stabilizing effects, and preservation of respiratoryfunction. The aim of this review is to present the most recent topics regarding the advantages in using dexmedetomidine in clinical anesthesia and intensive care, while discussing the controversial issues of its harmful effects.
 Introduction |   | |

α 2-adrenergic receptor (α 2-AR) agonists have been successfully used in several clinical settings in view of diverse actions which includesedation, analgesia, anxiolysis, perioperative sympatholysis, cardiovascular stabilizing effects, reduced anesthetic requirements, and preservation of respiratory function. [1] Dexmedetomidine is a relatively new drug approved at the end of 1999 by the Food and Drug Administration (FDA) for humans use for short-term sedation and analgesia (<24 hours) in the intensive care unit (ICU). Dexmedetomidineis a useful sedative agent with analgesic properties, hemodynamic stability and ability to recover respiratory function in mechanically ventilated patients facilitating early weaning. [2] Besides being a new modality of sedation and analgesia in ICU patient management, [3] it has been studied in several other perioperative settings, which will be discussed.

   Chemical Structure |   | |Dexmedetomidine is the dextrorotatory S-enantiomer of medetomidine, an agent used in veterinary medicine. [4] It is chemically (S)-4-[1-(2,3-dimethylphenyl) ethyl]-3H-imidazole [Figure 1].
| Figure 1: Chemical structure of dexmedetomidine
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   Mechanism of Action |   | |

α 2-AR agonists produce clinical effects after binding to G-Protein-coupled α 2-AR, of which there are three subtypes(α 2A, α 2B, and α 2C) with each having different physiological functions and pharmacological activities. These receptor subtypes are found ubiquitously in the central, peripheral, and autonomic nervous systems, as well as in vital organs and blood vessels. [5] Dexmedetomidine is 8 to 10 times more selective towards α 2-AR than clonidine. [6] Neither clonidine nor dexmedetomidine is totallyselective for any one of the α 2-AR subtypes, but dexmedetomidine seems to have higher α2A-AR and α 2C-AR affinity than clonidine. [7]

Locus ceruleus of the brain stem is the principal site for the sedative action and spinal cord is the principal site for the analgesic action, both acting through α 2A-AR. In the heart, the dominant action of α 2-AR agonists is a decrease in tachycardia (throughblocking cardioaccelerator nerve) and bradycardia via α 2A-AR (through a vagomimetic action). In the peripheral vasculature, there is sympatholysis-mediated vasodilatation and smooth muscle cells receptor-mediated vasoconstriction. [8] The mechanism for the antishivering and diuretic actions has yet to be established firmly [9].

The responses to activation of the receptors in other areas includedecreased salivation, decreased secretion, and decreased bowel motility in the gastrointestinal tract; contraction of vascular and other smooth muscle; inhibition of renin release, increased glomerular filtration, and increased secretion of sodium and water in the kidney; decreased intraocular pressure; and decreased insulin release from the pancreas.[10] Combining all these effects, dexmedetomidineavoids some of the side effects of multiagent therapies.

   Pharmacokinetics |   | |

Absorption and distribution

Dexmedetomidine exhibits linear pharmacokinetics in the recommended dose range of 0.2 to 0.7 μg/ kg/ hr administered as intravenous infusion up to 24 hours. The distribution phase is rapid, with a half-life of distribution of approximately 6 minutes and elimination half...