Dexmedetomidine (Precedex)

Indications

Procedural Sedation (see Sedation, [[Sedation]])

  • Bone Marrow Biopsy (see Bone Marrow Biopsy, [[Bone Marrow Biopsy]])
  • Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])
  • Endoscopy
    • Colonoscopy (see Colonoscopy, [[Colonoscopy]]): dexmedetomidine decreases sedative and analgesic requirements
    • Esophagogastroduodenoscopy (EGD) (see Esophagogastroduodenoscopy, [[Esophagogastroduodenoscopy]])
  • Fine Needle Aspiration (FNA) of Mass/Lesion
  • Foreign Body Extraction: particularly in pediatric populations
  • Surgery: dexmedetomidine decreases inhalational anesthetic, sedative, and analgesic requirements

Sedation in the Intensive Care Unit (ICU) (see Sedation, [[Sedation]])

  • Clinical Efficacy
    • Dexmedetomidine (Precedex) to Lessen ICU Agitation (DahLIA) Trial: Comparison of Dexmedetomidine to Placebo in Agitated Delirium in Mechanically-Ventilated Patients in the Intensive Care Unit (JAMA, 2016) [MEDLINE]
      • Dexmedetomidine Increased Ventilator-Free Hours at 7 Days, as Compared to Usual Care
      • Dexmedetomidine Decreased Time to Extubation and Accelerated Resolution of Delirium

Intoxication/Withdrawal

  • Acute Cocaine Intoxication (see Cocaine, [[Cocaine]])
    • Dexmedetomidine is Effective in Treatment of the Cardiovascular Effects of Cocaine Intoxication (J Am Coll Cardiol, 2007) [MEDLINE]
  • Ethanol Withdrawal (see Ethanol, [[Ethanol]]): used as an adjunct to benzodiazepines
    • Dexmedetomidine Decreases Benzodiazepine Dosing, Decreases Alcohol Withdrawal Scoring, and Blunts Hyperadrenergic Cardiovascular Responses (Ann Intensive Care, 2012) [MEDLINE]: adjunct to benzodiazepines

Other Uses

  • Cancer-Related Intractable Pain/Agitation/Delirium (J Pain Palliative Care Pharmacotherapy, 2006) [MEDLINE]

Pharmacology

  • α2-Adrenergic Receptor Agonist (see α2-Adrenergic Receptor Agonists, [[α2-Adrenergic Receptor Agonists]]): sedative, analgesic, sympatholytic, and anxiolytic effects, without significant respiratory depression
    • Similar to Clonidine (see Clonidine, [[Clonidine]])
  • Use of Dexmedetomidine Beyond 24 Hrs: associated with tachyphylaxis and dose-related increase in adverse reactions
  • Properties
    • Analgesic Effect
    • Anxiolytic Effect
    • Decreases Intracranial Pressure
    • Sedative Effect
    • Sympatholytic Effect
    • No Effect on Seizure Threshold
    • No Significant Respiratory Depression

Pharmacokinetics

  • Half-Life: 2 hrs
  • Dexmedetomidine Does Not Accumulate with Prolonged Infusion

Metabolism

  • Hepatic Glucuronidation and Oxidation: no active metabolites

Administration

  • IV Drip: 0.1-1.0 mcg/kg/hour
    • Although an initial bolus may be administered, this is not typically used

Dose Adjustment

  • Hepatic: dose-adjustment may be required in liver disease, although dexmedetomidine is typically dosed to effect
  • Renal

Adverse Effects

Cardiovascular Adverse Effects

  • Asystole (see Asystole, [[Asystole]])
  • Hypotension (see Hypotension, [[Hypotension]])
  • Sinus Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]])
  • Transient Hypertension (see Hypertension, [[Hypertension]]): usually observed initially, followed by hypotension

Gastrointestinal Adverse Effects

Other Adverse Effects

  • Dry Mouth (Xerostomia) (see Xerostomia, [[Xerostomia]])

References

  • Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Crit Care Med. 1995;23:1596-1600
  • Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335:1864-1869 [MEDLINE]
  • The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114:541-548
  • Sedation, where are we now? Intensive Care Med 1999; 25:137-139
  • Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471-1477 [MEDLINE]
  • Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion. Crit Care Med. 2000;28:1631-1634
  • Short-term lorazepam infusion and concern for propylene glycol toxicity. Pharmacotherapy 2001; 21:1140
  • Severe hyperosmolar metabolic acidosis due to a large dose of intravenous lorazepam. N Engl J Med 2002; 346:1253
  • The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med. 2003;168:1457-1461 [MEDLINE]
  • Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med. 2004;32:1272-1276 [MEDLINE]
  • Dexmedetomidine a novel analgesic with palliative medicine potential. J Pain and Palliative Care Pharmacotherapy 2006; 20 (2): 23–7. doi:10.1080/J354v20n02_05 [MEDLINE]
  • Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med 2004; 32:1709-1714
  • Propofol infusion syndrome. Anaesthesia. 2007;62:690-701
  • Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial”. JAMA 2007; 298 (22): 2644–53 [MEDLINE]
  • Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol 2007; 50 (7): 626–33. doi:10.1016/j.jacc.2007.03.060 [MEDLINE]
  • Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34 [MEDLINE]
  • Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care 2009;13:R75 [MEDLINE]
  • Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial”. JAMA 2009; 301 (5): 489–99 [MEDLINE]
  • Sedation Management in Australian and New Zealand Intensive Care Units: Doctors’ and Nurses’ Practices and Opinions”. Am J Crit Care 2009; 19 (3): 285–95 [MEDLINE]
  • A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med 2010; 38 (2): 497–503 [MEDLINE]
  • Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011 May;45(5):649-57. doi: 10.1345/aph.1P575. Epub 2011 Apr 26 [MEDLINE]
  • Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012 May 23;2(1):12. doi: 10.1186/2110-5820-2-12 [MEDLINE]
  • Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60 [MEDLINE]
  • American College of Critical Care Medicine: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013, 41:263-306 [MEDLINE]
  • DahLIA Trial: Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium. JAMA. 2016 Mar 15. doi: 10.1001/jama.2016.2707 [MEDLINE]