Skip to Main Content

INTRODUCTION

  1. Pharmacology

    1. Dexmedetomidine is a potent alpha-2- adrenergic receptor agonist. It shares structural and functional similarities with clonidine; however, the alpha-2/alpha-1 specificity ratio is eight times higher for dexmedetomidine. In addition, dexmedetomidine has more affinity for the alpha-2 A and C receptor subtypes, making it more effective than clonidine for sedation and analgesia. It can provide sedation with limited effects on respiratory depression. The sympatholytic effects are mediated via neuronal presynaptic alpha-2 receptors that provide negative feedback to reduce synaptic transmission.

    2. When given as an intravenous loading dose, followed by continuous infusion, the onset of action is 5–15 minutes and peak concentrations are achieved within 1 hour.

    3. The drug is rapidly distributed in a two-compartment model to a steady-state volume of distribution (Vd) of 118–152 L. Dexmedetomidine is 94% protein bound and has a distributional half-life of approximately 6 minutes following IV bolus and an elimination half-life of 2-2.67 hours.

    4. Dexmedetomidine undergoes complete biotransformation to inactive metabolites via N-glucuronidation, N-methylation, and hydroxylation via CYP P450 2D6.

  2. Indications

    1. Dexmedetomidine is FDA approved for sedation in mechanically intubated patients not to exceed 24 hours in adults. It is also approved for use in nonintubated adults prior to and/or during surgical and other procedures. There is no FDA-approved indication in pediatrics despite its wide use.

    2. Specific clinical conditions where it has been used include sedation for critically ill patients; sedation for minimally invasive procedures; premedication for surgery; opioid, benzodiazepine, and ethanol withdrawal states; fentanyl- or sufentanil-induced cough; and postanesthetic shivering. It may have potential neuroprotective use in neurological surgery due to its stable hemodynamics.

  3. Contraindications

    1. No specific contraindications exist. However, dose reductions are recommended in patients with impaired liver function and patients older than 65 years. Caution is also advised in patients with advanced heart block and/or severe ventricular dysfunction.

  4. Adverse effects

    1. Bradycardia and hypotension are the most common dose-dependent and clinically important adverse effects. Hypotension may be preceded by a brief phase of hypertension lasting 5–10 minutes.

    2. Most adverse effects occur during or shortly after the loading dose and may be minimized by slowing or omitting the loading dose. More pronounced effects may occur in patients older than 65 years and those with diabetes mellitus, advanced heart block, chronic hypertension, hypovolemia, and/or ventricular dysfunction.

    3. There are postmarketing reports of other cardiovascular (atrial fibrillation, AV block, ventricular arrhythmias), CNS (agitation, confusion, delirium, convulsions), and respiratory (apnea, bronchospasm, pulmonary congestion) adverse effects.

    4. Abrupt cessation of dexmedetomidine infusion has resulted in a rebound tachycardia and hypertension. Other drug withdrawal symptoms including nausea, vomiting, and agitation have been reported.

    5. Prolonged administration (>24 hours) may lead to tolerance (tachyphylaxis), requiring higher doses.

    6. Use in pregnancy. FDA Category C. No human data exist for use in labor or in breast-feeding mothers.

  5. Drug or laboratory interactions

    1. Use caution when administering dexmedetomidine with other drugs known to cause bradycardia or hypotension.

    2. Despite the high protein binding of dexmedetomidine, no significant displacement of warfarin, phenytoin, digoxin, theophylline or propranolol was evident when studied.

  6. Dosage ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.