Indications
Cocaine Intoxication (see Cocaine)
Clinical Efficacy
- Dexmedetomidine is Effective in Treatment of the Cardiovascular Effects of Cocaine Intoxication (J Am Coll Cardiol, 2007) [MEDLINE]
Alcohol (Ethanol) Withdrawal (see Ethanol)
Clinical Efficacy
- 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
Cancer-Related Intractable Pain/Agitation/Delirium (J Pain Palliative Care Pharmacotherapy, 2006) [MEDLINE]
Clinical Efficacy
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Post-Renal Transplant (see Renal Transplant)
Clinical Efficacy
- Trial of Dexmedetomidine Post-Renal Transplant (JAMA Netw Open. Published online June 3, 2022. doi:10.1001/jamanetworkopen.2022.15217 [MEDLINE]
- 24-hour Perioperative Dexmedetomidine Decreased the Incidence of Delayed Graft Function After Donation-After-Cardiac-Death Renal Transplant
Procedural Sedation (see Sedation)
- Bone Marrow Biopsy (see Bone Marrow Biopsy)
- Bronchoscopy (see Bronchoscopy)
- Endoscopy
- Colonoscopy (see Colonoscopy): dexmedetomidine decreases sedative and analgesic requirements
- Esophagogastroduodenoscopy (EGD) (see 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)
Rationale
- Need for Sedation While Intubated on Invasive Mechanical Ventilation
- Due to a Lack of Respiratory Depression, Dexmedetomidine May Also Be Used in the Setting of Ventilator Weaning and Extubation (see Invasive Mechanical Ventilation-Weaning)
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
- Study of Predictors of Patient Undergoing Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial from National Quality Improvement Data (Chest, 2022) [MEDLINE]
- Population Included Patients from 68 Intensive Care Units
- Spontaneous Awakening Trial: n = 4,847
- Spontaneous Breathing Trial: n = 4,936
- Factors Associated with Higher Odds of a Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial
- Documented Target Sedation Level (Adjusted Odds Ratio: 1.68; 95% CI: 1.41-2.01; Adjusted Odds Ratio: 1.46; 95% CI: 1.24-1.72)
- Dexmedetomidine Administration (Adjusted Odds Ratio: 1.23; 95% CI: 1.05-1.45; Adjusted Odds Ratio: 1.52; 95% CI: 1.27-1.80)
- More Frequent Level of Arousal Assessments (Adjusted Odds Ratio: 1.22; 95% CI: 1.03-1.43; Adjusted Odds Ratio: .32; 95% CI: 1.13-1.54)
- Physical Restraint Use (Adjusted Odds Ratio: 1.63; 95% CI: 1.42-1.87; Adjusted Odds Ratio: 1.83; 95% CI,: 1.60-2.09)
- Factors Associated with Lower Odds of a Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial
- Benzodiazepine Administration (Adjusted Odds Ratio: 0.83; 95% CI: 0.72-0.95; Adjusted Odds Ratio: 0.67; 95% CI: 0.59-0.77)
- Deep Sedation/Coma (Adjusted Odds Ratio: 0.69; 95% CI: 0.60-0.80; Adjusted Odds Ratio: 0.33; 95% CI: 0.28-0.37)
- Ketamine Administration (Adjusted Odds Ratio: 0.34; 95% CI: 0.16-0.71; Adjusted Odds Ratio: 0.40; 95% CI: 0.18-0.88)
- Population Included Patients from 68 Intensive Care Units
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
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)
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)
- Epidemiology
- 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
- Epidemiology
- 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
Risk Factors
- Continuous Dexmedetomidine Infusion for a Longer Duration
- Higher Cumulative Daily Dexmedetomidine Dose (>12 mcg/kg/Day)
- Higher Peak Dexmedetomidine Rate (>0.8 mcg/kg/hr)
- History of Hypertension (see Hypertension)
Clinical Manifestations
- Agitation (see Agitation)
- Delirium (see Delirium)
- Hypertension (see Hypertension)
- Tachycardia (see Sinus Tachycardia)
Prevention
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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