Background      Dexmedetomidine is a drug with sedative and analgesic properties that is approved for parenteral use (brand name Precedex) in non-intubated adults and children undergoing surgery or other medical procedures and in intubated patients in the intensive care unit (ICU) unit. In 2022, dexmedetomidine was also approved for sublingual use (brand name Igalmi) to manage acute agitation associated with schizophrenia or bipolar disorder. There has been increasing interest in its off-label use in other end-of-life settings such as delirium, adjunctive analgesia, insomnia, and controlled sedation. This Fast Fact reviews dexmedetomidine’s use relevant to palliative care.

Pharmacology     Dexmedetomidine is a relatively selective, alpha-2 adrenergic receptor agonist. Initially its use in the ICU was limited to only 24 hours due to concerns with hypotension in comparison to propofol, however, published reports have demonstrated its overall safety and efficacy for longer periods (1-4). Parentally, it can be given as an infusion (e.g., for ventilator sedation) or a bolus (e.g., for procedural sedation). Its parenteral onset of action is 5-10 min, peak affect 15-30 min, with duration of action of 60-120 min after a bolus; sublingual onset of action 20-30 minutes. It is 94% protein bound and metabolized in the liver to renally excreted metabolites. Its elimination half-life in healthy adults is ~2 hours (5). Bioavailability is high parenterally and sublingually (72%). Besides sedation and analgesia, its major clinical effects are related to the generally sympatholytic effects of alpha-2 agonism: bradycardia and hypotension. When administered at standard infusion rates, a transient increase in blood pressure often occurs followed by a sustained lower blood pressure of ~10-20% below baseline (6). Unlike most sedatives, it is not known to suppress respiratory drive at clinically relevant doses (7,8). Sublingual use is also associated with QTc prolongation, oral numbness, and dry mouth (9).

Clinical findings – mechanically ventilated patients     There has been much interest in investigating dexmedetomidine’s promise as a superior sedative for mechanically ventilated patients in the ICU. Results have been mixed as to whether it provides a meaningful improvement over other agents, notably benzodiazepines and propofol. Some studies have shown dexmedetomidine use is associated with less delirium, shorter ICU lengths of stay, and decreased time to extubation (10-15), but these finding have not been universal (12). Compared to propofol and midazolam, at any given level of sedation, dexmedetomidine does improve patients’ ability to communicate pain (10,13). In all these studies, bradycardia was found to be significantly worse in dexmedetomidine patients compared to benzodiazepines or propofol.

Clinical findings – pain     Sub-sedating doses of dexmedetomidine have been used as an analgesic. Two case reports in patients with severe, refractory cancer pain found the temporary use (~3-6 days) of dexmedetomidine at 0.2-0.6 mcg/kg/hour greatly reduced the patient’s pain, while alternative analgesic modalities were explored (1,16). Since then, two small, randomized trials have been published in which dexmedetomidine demonstrated effectiveness in managing cancer related pain, but it was no more effective when compared to standard use of opioids (17,18). There has also been an intriguing case series published, describing the use of dexmedetomidine for suspected opioid-induced hyperalgesia (OIH; see Fast Fact #142) (3). Patients on high-dose opioids with suspected OIH were transferred to the ICU, if not already there, and given dexmedetomidine at rates of 0.2-0.7 mcg/kg/hour for 2-7 days. Opioid doses subsequently were decreased by ~70% with apparently equal or better analgesia. The authors suspected that dexmedetomidine “’reboots’ opioid sensitivity,” although the true mechanism of action for this effect, if even real, has not been determined.

Clinical findings – symptoms at the end-of-life     Given the observation that patients sedated with dexmedetomidine appear to remain more arousable and interactive compared to patients sedated with benzodiazepines, there has been interest in using dexmedetomidine to manage delirium as well as provide sedation, anxiolysis, insomnia, and analgesia for patients with severe symptoms near the end-of-life, while avoiding the need to deeply sedate patients to unconsciousness (see Fast Fact #106 and Fast Fact #107) (9,19,20). An observational study of nine pediatric patients with intractable symptoms from advanced cancer and non-cancer illnesses showed significant reduction in pain scores in patients treated with parenteral dexmedetomidine (21). In a phase 3, double-blind, randomized study, sublingual dexmedetomidine at doses of 120 and 180 micrograms reduced agitation safely and effectively in patients with bipolar disorder (22).  Approved sublingual use is limited to patients with schizophrenia and bipolar disorder, but there is interest in its potential role in managing terminal agitation and restlessness.

Cost: Parenteral dexmedetomidine (Precedex) is now available as a generic. Cost is still variable but ranges from $10-$40 per vial in a 200 mcg vial for $55.00 (23).  For comparison, the average daily cost of parenteral dexmedetomidine as an ICU sedative is about 2 times the cost of propofol and 4 times the cost of midazolam. Sublingual dexmedetomidine is not available as a generic formulation and pricing is about $100 per dose. This makes it cost prohibitive for most hospices and many hospitals.

References 

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3. Belgrade M, Hall S. Dexmedetomidine Infusion for the Management of Opioid-Induced Hyperalgesia.  Pain Med. 2010:1-8.
4. Devabhakthuni, S. et al, Evaluation of Dexmedetomidine: Safety and Clinical Outcomes in Critically Ill Trauma Patients, Journal of Trauma, Injury, Infection and Critical Care, 2011.
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11. MacLearen R, Preslaski CR, et al.  A randomized, double-blind pilot study of edexmedetomidine versus midazolam for intensive care unit  sedation. J Intensive Care Med 2015; 30:167-175.
12. Shehabi Y, Grant P, Wolfenden H, Hammond N et al.  Prevalence of Delirium with Dexmedetomidine Compared with Morphine Based Therapy after Cardiac Surgery.  Anesthesiology.  2009;111:1075-84.
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14. Riker RR, Shehabi Y, Bokesch PM et al.  Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial.  JAMA.  2009;301(5):489-99.
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16. Hilliard N, Brown S, Mitchinson S. A case report of dexmetetomidine used to treat intractable pain and delirium in a tertiary palliative care unit. Pall Med 2015; 29:278-281.
17. Yamout R, Viallard M, Hoteit S, et al. Does the addition of dexmedetomidine to morphine have any clinical benefit on the treatment of pain in patients with metastatic cancer? A pilot study. Prog Palliat Care 2021;29:1–6.
18. Torres OC, Allier MG, Olvera MJ. Comparación entre dexmedetomidina en infusión intravenosa vs. lidocaína en infusión intravenosa para el control de dolor refractario a tratamiento opioide en pacientes de cuidados paliativos. Rev. Soc. Esp. Dolor 2015;22:7–12.
19. Soares LG, Naylor C, Martins MA, Peixoto G.  Letter: Dexmedetomidine: A New Option for Intractable Distress in the Dying.  J Pain Symptom Manage.  2002;24(1):6-8.
20. Hillard NK, Brown SB. Pilot Study Comparing Treatment With Dexmedetomidine to Midazolam for Symptom Control in Advanced Cancer Patients. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2013 Jul 9]. Available from: http://clinicaltrials.gov/ct2/show/NCT01687751?term=dexmedetomidine+palliative&rank=1.  NLM Identifier: NCT01687751.
21. Burns J, Jackson K, Sheehy KA, et al.  The use of dexmedetomidine in pediatric palliative care: a preliminary study. Journal of Palliative Medicine 2017; 20(7):1390-1403.
22. 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.
23. Dexmedetomidine for Sedation in the ICU or PICU: A Review of Cost-Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Dec 17. APPENDIX 1, COST COMPARISON OF ICU SEDATIVES.
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Authors’ Affiliations: University of Maryland, Baltimore, MD (KW); Duquense University, Pittsburgh, PA (KM); University of Minnesota Medical School and Fairview Health Services, Minneapolis, MN (DAR).
Conflict of Interest Disclosure: The authors have disclosed no relevant conflicts of interest.
Version History:  First published May 2014. Re-copy-edited in September 2015 by Sean Marks MD; reviewed and updated again in September 2025.