dexmedetomidine (Precedex)
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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]
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
- metabolized by glucoronidaton & cyt P450 2A6
- strongly inhibits cyt P450 2D6
- weakly inhibits cyt P450 1A2, cyt P450 3A4, cyt P450 2C8
- volume of distribution 118 liters
- protein-binding 94%
- 1/2life 6 minutes
- excretion of metabolites in urine (95%), feces (4%)
Monitor
pulse, respiration, rhythm, blood pressure, consciousness
Adverse effects
- common > 10%
- hypotension (30%)
- nausea (11%)
- less common (1-10%)
- bradycardia (8%)
- atrial fibrillation (7%)
- pain (3%)
- anemia (3%)
- leukocytosis (2%)
- oliguria (2%)
- hypoxia (6%)
- pulmonary edema (2%)
- pleural effusion (3%)
- infection (2%)
- thirst (2%)
- drug adverse effects of adrenergic receptor agonists
- drug adverse effects of alpha-adrenergic receptor agonists
- drug adverse effects of psychotropic agents
- drug adverse effects of sedatives
- drug adverse effects of sympathomimetic(s)
Drug interactions
- drugs that inhibit cyt P450 2A6 prolong 1/2life of dexmedetomidine
- 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
- 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]
More general terms
References
- ↑ UpToDate 13.2
- ↑ Venn M et al, Intensive Care Med 2003; 29:201 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12594584
- ↑ 3.0 3.1 3.2 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: https://www.ncbi.nlm.nih.gov/pubmed/18073360
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/22436955
- ↑ 5.0 5.1 5.2 5.3 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: https://www.ncbi.nlm.nih.gov/pubmed/26975647
Ely EW, Pandharipande PP. The evolving approach to brain dysfunction in critically ill patients. JAMA 2016 Apr 12; 315:1455 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26976552 - ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/27542303
- ↑ 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28322414 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2612911
- ↑ 8.0 8.1 Shehabi Y, Howe BD, Bellomo R et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 2019 May 19; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31112380 https://www.nejm.org/doi/10.1056/NEJMoa1904710
- ↑ 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/35191924 https://jamanetwork.com/journals/jama/fullarticle/2789315
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=68602
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60612
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5311068
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=123602
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=68601