Dexmedetomidine (Precedex)


Indications

Procedural Sedation (see Sedation)

  • Bone Marrow Biopsy (see Bone Marrow Biopsy)
  • Bronchoscopy (see Bronchoscopy)
  • Endoscopy
  • 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)

Clinical Efficacy

  • Dexmedetomidine 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
  • Meta-Analysis of Dexmedetomidine in ICU Sedation (Anaesth Crit Care Pain Med, 2016)[MEDLINE]
    • Dexmedetomidine was Associated with a 48 hr Reduction in ICU Length of Stay, Mechanical Ventilation Duration, and Duration of Delirium: despite significant heterogeneity among the studies
    • Dexmedetomidine was Associated with an Increased Risk of Bradycardia and Hypotension

Intoxication/Withdrawal

Acute Cocaine Intoxication (see Cocaine)

  • Clinical Efficacy
    • Dexmedetomidine is Effective in Treatment of the Cardiovascular Effects of Cocaine Intoxication (J Am Coll Cardiol, 2007) [MEDLINE]
  • Ethanol Withdrawal (see Ethanol): used as an adjunct to benzodiazepines

Alcohol Withdrawal (see Ethanol)

  • Dexmedetomidine Decreases Benzodiazepine Dosing, Decreases Alcohol Withdrawal Scoring, and Blunts Hyperadrenergic Cardiovascular Responses (Ann Intensive Care, 2012) [MEDLINE]
    • Dexmedetomidine Can Be Used as an Adjunct to Benzodiazepines
  • Prospective Randomized Trial of Dexmedetomidine as Add-On Therapy to Lorazepam in Severe Alcohol Withdrawal (Crit Care Med, 2014) [MEDLINE]
    • Adjunctive Dexmedetomidine Maintains Symptom Control in Severe Alcohol Withdrawal, Decreasing Short-Term (But Not Long-Term) Lorazepam Use When Using a Symptom-Triggered Protocol
    • Monitoring for Bradycardia is Required with Dexmedetomidine and is Less Significant with Lower Infusion Rates
  • Retrospective Cohort Study of Dexmedetomidine vs Benzodiazepines in Alcohol Withdrawal (Pharmacotherapy, 2014) [MEDLINE]
    • Adjunctive Dexmedetomidine Manifested a Benzodiazepine-Sparing Effect in Alcohol Withdrawal
    • Although the Total Cost of Hospitalization was Similar Between the Groups, Dexmedetomidine was Associated with a Higher Study Drug Cost Per Patient

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)

  • 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

Administration

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)

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

Other Adverse Effects


References

Indications-Alcohol Withdrawal

Indications-Intensive Care Unit Sedation