Introduction
Delirium and agitation are highly distressing symptoms in patients with advanced cancer and are often challenging to manage when refractory to antipsychotics and benzodiazepines. Escalation of these agents may be limited by oversedation, paradoxical agitation, and worsening delirium (Mancuso et al. Reference Mancuso, Tanzi and Gabay2004). Dexmedetomidine, a highly selective α2-adrenergic agonist, is licensed for short-term intravenous sedation in intensive care and procedural settings. Its ability to reduce agitation while preserving arousability has led to growing interest in off-label use in palliative care (Gerlach and Murphy Reference Gerlach and Murphy2011).
Existing literature describes dexmedetomidine use for refractory agitation (Yu et al. Reference Yu, Schellenberg and Alleyne2023), hyperactive delirium and pain crises (Thomas et al. Reference Thomas, Lo and Nangati2021), as well as dyspnea (Li et al. Reference Li, Cui and Wang2023). The DREAMS randomized controlled trial comparing dexmedetomidine with midazolam for end-of-life sedation demonstrated comparable sedative efficacy with lower delirium scores in the dexmedetomidine group (Thomas et al. Reference Thomas, Barclay and Mansfield2025). However, current publications in palliative care largely focus on patients with prognoses of days to weeks and inpatient end-of-life sedation. Guidance is limited for patients with longer prognoses, where the clinical goal is often symptom stabilization rather than continuous deep sedation.
Prolonged dexmedetomidine use presents practical challenges, including the need for continuous intravenous administration and close monitoring, which limits long-term use and hospital discharge. Clonidine, an orally administered α2-adrenergic agonist with similar sympatholytic properties, offers a potential strategy for transitioning patients off dexmedetomidine while maintaining symptom control. Other than its use in critical care to mitigate dexmedetomidine withdrawal (Glaess et al. Reference Glaess, Attridge and Christina Gutierrez2020; Rajendraprasad et al. Reference Rajendraprasad, Wheeler and Wieruszewski2023), there is currently minimal literature describing structured dexmedetomidine-to-clonidine transitions in palliative care populations.
We present a case illustrating the use of dexmedetomidine as a stabilizing bridge for refractory pain and delirium in a patient with a prognosis of months, followed by a cross-taper to oral clonidine. This enabled symptom stabilization, completion of interventional pain therapy with radiation, and discharge home with sustained outpatient symptom control.
Case
A 45-year-old man with high-grade metastatic medullary thyroid carcinoma with extensive pulmonary metastases and osseous involvement of the pelvis and right scapula was admitted to the inpatient palliative care unit for uncontrolled pain. His prognosis was estimated to be 1 year, and he was functionally independent prior to admission. He had a medical history of generalized anxiety disorder, opioid use disorder, and polysubstance use including benzodiazepines and stimulants. Prior to hospitalization, the patient reported taking morphine extended-release 1300 mg three times daily and hydromorphone 100 mg three times daily for cancer-related pain. These reported doses could not be independently verified, and the patient had a history of self-directed opioid dose adjustments. His symptoms were reportedly controlled on this regimen, but his pain worsened significantly as he attempted to self-taper his hydromorphone dose, prompting admission.
On admission, his home doses of morphine and hydromorphone were restarted with minimal effect on his pain. The hydromorphone dose increased with minimal benefit. He continued to report severe mixed nociceptive and neuropathic pain localizing to the shoulder and sternum, sites of known metastatic disease. Imaging demonstrated disease progression without evidence of pathological fracture. He was then transferred to the inpatient palliative care unit where his opioids were consolidated to an intravenous morphine infusion with minimal benefit to his pain. Over the next 5 days, dexamethasone 4 mg was added as an adjunct, and a gradual titration of methadone to 20 mg every 8 hours was completed. During this time, he became increasingly delirious and agitated to the point that radiation therapy for pain control was unable to proceed. On day 6, the morphine infusion was converted to a fentanyl infusion, but despite titration to 100 µg/hr, his pain remained poorly controlled, and his agitation continued to worsen. An evaluation was undertaken to identify reversible contributors to his delirium. Head imaging demonstrated no evidence of intracranial metastases. Laboratory investigations, including metabolic and thyroid panels, were within normal limits. An infectious work-up was negative. The patient remained highly agitated and distressed despite pharmacological interventions to manage the agitation, including haloperidol, methotrimeprazine, and midazolam.
Given persistent agitation and opioid-refractory pain, dexmedetomidine was initiated with a bolus of 1 µg/kg followed by a continuous infusion starting at 0.2 µg/kg/hr and titrated to 0.6 µg/kg/hr. By the following morning, his agitation resolved, and he was calm, oriented, ambulatory, and engaging in meaningful conversation. His pain was markedly improved despite no change in his analgesics. He subsequently completed a course of palliative radiation for pain control. Although dexmedetomidine was effective in controlling agitation and pain, its continuous intravenous administration necessitated monitoring and effectively tethered the patient to the palliative care unit.
Given an estimated prognosis of several months and the patient’s preference to leave hospital, we attempted to wean the dexmedetomidine, but this caused a significant increase in his pain. We then pursued a cross-taper strategy with clonidine. Oral clonidine was initiated at 0.1 mg 3 times daily and titrated to 0.5 mg 4 times daily while the dexmedetomidine infusion was tapered in decrements of 0.1–0.2 µg/kg/hr over the course of 1 week. He tolerated this transition without recurrence of agitation, pain, or hemodynamic instability, allowing discontinuation of dexmedetomidine and discharge home with adequate symptom control. At follow-up, the patient reported ongoing symptom stability and had independently weaned off clonidine after several weeks. He remained clinically stable for 5 months after discharge.
Discussion
Dexmedetomidine can serve as an effective stabilizing therapy for refractory pain and delirium in selected palliative care patients with longer prognoses, functioning as a bridge rather than a modality for terminal sedation. By controlling agitation while preserving arousability, dexmedetomidine allows time to assess reversible contributors and implement additional treatments. Transition to oral clonidine can facilitate discontinuation of intravenous dexmedetomidine, support discharge, and enable sustained outpatient symptom control.
This case illustrates the use of dexmedetomidine as a stabilizing bridge for refractory pain and delirium in a patient with a prognosis of months, rather than as a modality for palliative sedation. Dexmedetomidine achieved rapid control of agitation and distress while maintaining arousability, enabling sufficient symptom stabilization for diagnostic reassessment and radiation therapy.
In this case, the patient’s presentation raised concern for opioid-induced hyperalgesia (OIH), given that he reported extremely high outpatient opioid doses, escalation of pain despite increasing opioids, and worsening agitation. OIH is characterized by paradoxical pain amplification mediated by central sensitization and N-methyl-D-aspartate (NMDA) receptor activation (Mercadante Reference Mercadante2023). In this case, fluctuating delirium and severe agitation limited bedside assessment of classic features, such as diffuse allodynia or hyperalgesia beyond the original pain distribution, and the diagnosis could only be suspected retrospectively. Dexmedetomidine enabled symptom stabilization while potential contributors to delirium and pain were systematically addressed.
Dexmedetomidine has mechanistic properties that support this role. In addition to α2-adrenergic agonism and sympatholysis, preclinical studies suggest attenuation of OIH through modulation of NMDA receptor-related signaling pathways (Funai et al. Reference Funai, Pickering and Uta2014; Yuan et al. Reference Yuan, Sun and Chen2017). Clinical reports describe opioid dose reduction and improved symptom control in patients with suspected OIH treated with dexmedetomidine infusions (Belgrade and Hall Reference Belgrade and Hall2010; Hofherr et al. Reference Hofherr, Abrahm and Rickerson2020). Similar prolonged use has been reported in palliative patients with polysubstance use, achieving symptom control while preserving wakefulness and function (Dieudonné Rahm et al. Reference Dieudonné Rahm, Kemicha and Papasokrati2023). Despite its effectiveness, dexmedetomidine’s requirement for continuous intravenous administration and monitoring limits feasibility for patients with longer prognoses. Withdrawal symptoms, including agitation, tachycardia, and hypertension, have been reported following prolonged infusions, particularly when the infusion is stopped abruptly (Kim et al. Reference Kim, McLaughlin and Romero2024; Mason et al. Reference Mason, Mesarwi and Le2025). These limitations highlight the need for a feasible transition strategy.
Clonidine, an orally administered α2-adrenergic agonist with a longer half-life, has been used in critical care as a step-down agent to facilitate dexmedetomidine discontinuation. Observational studies and reviews describe heterogeneous protocols involving gradual dexmedetomidine taper with initiation of oral clonidine, typically at doses of 0.1–0.3 mg every 6–8 hours (Glaess et al. Reference Glaess, Attridge and Christina Gutierrez2020). A recent retrospective cohort study reported successful dexmedetomidine discontinuation within 24 hours in over half of Intensive care unit patients following clonidine initiation (Basappa et al. Reference Basappa, Block and Vallabh2025). However, these data are derived exclusively from critically ill populations, and palliative-specific evidence is lacking. In this case, a gradual clonidine cross-taper over 1 week enabled discontinuation of dexmedetomidine without recurrence of agitation, pain, or hemodynamic instability, allowing discharge home with sustained outpatient symptom control.
Strengths and limitations
To our knowledge, this is among the first case reports describing a dexmedetomidine-to-clonidine transition in a functionally independent patient with a prognosis of months in the palliative care setting. The case highlights dexmedetomidine’s role as a reversible stabilizing therapy rather than end-of-life sedation and suggests clonidine may serve as a practical outpatient bridge in selected patients. Additional studies are needed to define optimal patient selection, dosing strategies, and determine the safety of α2-agonist transitions in palliative care populations.
Acknowledgments
There are no specific acknowledgments.
Author contributions
K.L. was involved with data collection, drafting, and revising the manuscript. B.L. was involved with drafting and revising the manuscript. S.M. was involved with data collection, drafting, and revising the manuscript. S.N. was involved with data collection, drafting, and revising the manuscript.
Funding
This report did not receive any specific grant or funding.
Competing interests
All authors declare no conflicts of interest.
Ethical approval
Institutional ethics approval was not required.
Ethics and consents
Patient written informed consent was obtained for this case report.
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