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dexmedetomidine (Precedex)

Indications: - initial sedation after endotracheal intubation & mechanical ventilation in an ICU setting - may diminish delirium & coma in mechanically-ventilated patients [3,5] - may diminish postoperative delirium [6] - may not be beneficial after extubation - sublingual dexmedetomidine reduces mild to moderate agitation in patients with bipolar disorder [9] * dexmedetomidine in patients with sepsis did not improve either ventilator-free days or 28-day mortality [7] Contraindications: - not indicated for infusions > 24 hours - no mortality benefit as sole sedating agent for critically ill patients [8] Pregnancy category: C Dosage: - IV infusion - loading dose of 1 ug/kg over 10 minutes - maintenance 0.2-0.7 ug/kg/hour - consider dose reduction in the elderly - sublingual 120 ug, 180 ug [9] Solution must be diluted with normal saline prior to administration Pharmacokinetics: 1) metabolized by glucoronidaton & cyt P450 2A6 2) strongly inhibits cyt P450 2D6 3) weakly inhibits cyt P450 1A2, cyt P450 3A4, cyt P450 2C8 4) volume of distribution 118 liters 5) protein-binding 94% 6) 1/2life 6 minutes 7) excretion of metabolites in urine (95%), feces (4%) Monitor: pulse, respiration, rhythm, blood pressure, consciousness Adverse effects: 1) common > 10% a) hypotension (30%) b) nausea (11%) 2) less common (1-10%) a) bradycardia (8%) b) atrial fibrillation (7%) c) pain (3%) d) anemia (3%) e) leukocytosis (2%) f) oliguria (2%) g) hypoxia (6%) h) pulmonary edema (2%) i) pleural effusion (3%) j) infection (2%) k) thirst (2%) Drug interactions: 1) drugs that inhibit cyt P450 2A6 prolong 1/2life of dexmedetomidine 2) dexmedetomidine prolong 1/2life of drugs metabolized by cyt P450 2D6 - dextromethorphan, fluoxetine, lidocain, mirtazapine, nefazodone, paroxetine, risperidone, ritoniavir, thioridazine, tricyclic antidepressants, venlaxafine - prodrugs: tramadol, codeine, hydrocodone, oxycodone 3) dexmedetomidine may prolong 1/2life of drugs metabolized by P450 1A2, cyt P450 3A4, cyt P450 2C8 Mechanism of action: - alpha 2 adrenergic agonist - does not diminish respiratory drive [5] - may diminish delirium & coma in mechanically-ventilated patients [3,5]

Interactions

drug adverse effects of adrenergic receptor agonists

General

alpha-2 adrenergic receptor agonist sedative/hypnotic (tranquilizer)

Database Correlations

PUBCHEM correlations

References

  1. UpToDate 13.2
  2. Venn M et al, Intensive Care Med 2003; 29:201 PMID: 12594584
  3. Pandharipande PP et al, Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: The MENDS randomized controlled trial. JAMA 2007, 298:2644 PMID: 18073360
  4. Jakob SM et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: Two randomized controlled trials. JAMA 2012 Mar 21; 307:1151. PMID: 22436955
  5. Reade MC et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: A randomized clinical trial. JAMA 2016 Apr 12; 315:1460. PMID: 26975647 - Ely EW, Pandharipande PP. The evolving approach to brain dysfunction in critically ill patients. JAMA 2016 Apr 12; 315:1455 PMID: 26976552
  6. Su X, Meng ZT, Wu XH et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: A randomised, double-blind, placebo- controlled trial. Lancet 2016 Aug 16; PMID: 27542303
  7. Kawazoe Y, Miyamoto K, Morimoto T et al Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis. A Randomized Clinical Trial. JAMA. 2017 Apr 4;317(13):1321-1328 PMID: 28322414 http://jamanetwork.com/journals/jama/fullarticle/2612911
  8. Shehabi Y, Howe BD, Bellomo R et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 2019 May 19; PMID: 31112380 https://www.nejm.org/doi/10.1056/NEJMoa1904710
  9. Preskorn SH, Zeller S, Citrome L et al Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder. A Randomized Clinical Trial. JAMA. 2022;327(8):727-736 PMID: 35191924 https://jamanetwork.com/journals/jama/fullarticle/2789315