Indications

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Pharmacology

Dexmedetomidine is an α2-Adrenergic Receptor Agonist (see α2-Adrenergic Receptor Agonists)

• Similar to Clonidine (see Clonidine)
• Properties
  • Analgesic Effect
  • Anxiolytic Effect
  • Decreases Intracranial Pressure
  • Sedative Effect
  • Sympatholytic Effect
  • No Effect on Seizure Threshold
  • No Significant Respiratory Depression

Protein Binding

• Dexmedetomidine is Highly Protein Bound (Approximately 94%)

Pharmacokinetics

• Onset After IV Loading Dose: 5-10 min
  • Peak Effect After IV Loading Dose: 15-30 min
• Half-Life: 2 hrs
• Dexmedetomidine Does Not Accumulate with Prolonged Infusion

Metabolism

• Hepatic Glucuronidation and Oxidation
  • No Active Metabolites
  • Metabolites are Primarily Excreted in the Urine

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Administration

Intravenous (Maintenance for Sedation in the Intensive Care Unit) (see Sedation)

• Dose: 0.2-1.5 mcg/kg/hour
  • Although an Initial Bolus May Be Administered, this is Not Typically Used in Clinical Practice
  • Titrate by 0.2 mcg/kg/hr q30 min to Sedation Goal or Clinical Effect
  • Although Infusion Rates as High as 2.5 mcg/kg/hr Have Been Used in the Medical Intensive Care Unit Setting, Doses >1.5 mcg/kg/hr Do Not Provide Additional Clinical Efficacy (Intensive Care Med. 2003) [MEDLINE]
• Duration of Dexmedetomidine Use
  • Use of Dexmedetomidine Beyond 24 Hrs is Associated with Tachyphylaxis and Dose-Related Increase in Adverse Reactions
  • While the Manufacturer Recommends that Infusion Duration Not Exceed 24 hrs, Randomized Trials Have Demonstrated Efficacy and Safety Comparable to Lorazepam and Midazolam with Longer-Term Infusions of Up to 14 Days (JAMA, 2012)[MEDLINE] (NEJM, 2019)[MEDLINE]
  • Dexmedetomidine Withdrawal Syndrome (See Below)
    • History of Hypertension, Continuous Dexmedetomidine Infusion for a Longer Duration, Higher Cumulative Daily Dexmedetomidine Dose (>12 mcg/kg/Day), or Higher Peak Dexmedetomidine Rate (>0.8 mcg/kg/hr) Increase the Risk of Dexmedetomidine Withdrawal Symptoms (Hypertension, Tachycardia, Delirium, Agitation)
    • In Such Patients, Avoid Abrupt Dexmedetomidine Discontinuation and Wean Slowly While Monitoring for Withdrawal Symptoms (Crit Care Explor, 2019) [MEDLINE] (Pharmacotherapy, 2019) [MEDLINE] (J Crit Care, 2020) [MEDLINE]
• Use in the Setting of Setting of Ventilator Weaning and Extubation
  • Due to Lack of Respiratory Depression, Dexmedetomidine May Be Used in the Setting of Ventilator Weaning and Extubation (see Invasive Mechanical Ventilation-Weaning)

Dose Adjustment

• Hepatic: dose-adjustment may be required in liver disease
  • However, Dexmedetomidine is Typically Dosed to Effect
• Renal: none are specified in the manufacturer’s labeling
  • However, Pharmacokinetics are Not Significantly Different in Patients with Severe Renal Impairment (CrCl <30 mL/min)

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Adverse Effects

Cardiovascular Adverse Effects

• Asystole (see Asystole)
• Hypotension (see Hypotension)
  • Epidemiology
    • Bradycardia and Hypotension are More Common with Dexmedetomidine than with Other Sedatives (Such as Propofol, Lorazepam, and Midazolam)
• Sinus Bradycardia (see Sinus Bradycardia)
  • Epidemiology
    • Bradycardia and Hypotension are More Common with Dexmedetomidine than with Other Sedatives (Such as Propofol, Lorazepam, and Midazolam)
    • Bradycardia is More Common with Use of Loading Dose and with High Infusion Rate
• Transient Hypertension (see Hypertension): usually observed initially, followed by hypotension

Gastrointestinal Adverse Effects

• Nausea (see Nausea and Vomiting)

Other Adverse Effects

Dry Mouth (Xerostomia) (see Xerostomia)

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Dexmedetomidine Withdrawal Syndrome

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References

Indications-Alcohol Withdrawal

• 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]
• A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014 May;42(5):1131-9. doi: 10.1097/CCM.0000000000000141 [MEDLINE]
• Comparison of clinical outcomes in nonintubated patients with severe alcohol withdrawal syndrome treated with continuous-infusion sedatives: dexmedetomidine versus benzodiazepines. Pharmacotherapy. 2014 Sep;34(9):910-7. doi: 10.1002/phar.1448. Epub 2014 Jun 5 [MEDLINE]

Indications-Intensive Care Unit Sedation (see Sedation)

• 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
• Adverse events associated with sedatives, analgesics, and other drugs that provide patient comfort in the intensive care unit. Pharmacotherapy. 2005 May;25(5 Pt 2):8S-18S [MEDLINE]
• 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 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]
• Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth Crit Care Pain Med. 2016 Feb;35(1):7-15. doi: 10.1016/j.accpm.2015.06.012. Epub 2015 Dec 11 [MEDLINE]
• Factors Associated With Spontaneous Awakening Trial and Spontaneous Breathing Trial Performance in Adults With Critical Illness: Analysis of a Multicenter, Nationwide, Cohort Study. Chest. 2022 Sep;162(3):588-602. doi: 10.1016/j.chest.2022.01.018 [MEDLINE]

Indications-Post-Renal Transplant (see Renal Transplant)

• Effect of perioperative dexmedetomidine on delayed graft function following a donation-after-cardiac-death kidney transplant: a randomized clinical trial. JAMA Netw Open. Published online June 3, 2022. doi:10.1001/jamanetworkopen.2022.15217 [MEDLINE]

Administration

• A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. 2003 Feb;29(2):201-7. doi: 10.1007/s00134-002-1579-9 [MEDLINE]
• Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151-1160. doi:10.1001/jama.2012.304 [MEDLINE]
• Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506-2517. doi:10.1056/NEJMoa1904710 [MEDLINE]
• Incidence of dexmedetomidine withdrawal in adult critically ill patients: a pilot study. Crit Care Explor. 2019;1(8):e0035. doi:10.1097/CCE.0000000000000035 [MEDLINE]
• Incidence of rebound hypertension after discontinuation of dexmedetomidine. Pharmacotherapy. 2019;39(10):970-974. doi:10.1002/phar.2323 [MEDLINE]
• Identification of risk factors for hypertension and tachycardia upon dexmedetomidine discontinuation. J Crit Care. 2020;59:81-85. doi:10.1016/j.jcrc.2020.06.006 [MEDLINE]

Adverse Effects

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