Dexmedetomidine for hyperactive delirium at the end of life: An open-label single arm pilot study with dose escalation in adult patients admitted to an inpatient palliative care unit

Abstract

Background: Terminal delirium, specifically the hyperactive delirium subtype at the end of life, is common in palliative care patients. Standard care often involves sedation to alleviate distress. The alpha2-adrenoreceptor agonist dexmedetomidine may have promise in terminal delirium, due to its properties of decreasing delirium and permitting rousable sedation. Aim: This study aimed to describe the effect of dexmedetomidine on delirium and sedation, when delivered via continuous subcutaneous infusion (CSCI) in patients with terminal delirium. Design: The trial was prospectively registered in the ANZCTR database (ACTRN12618000658213) and conducted in accordance with CONSORT (pilot study extension). Twenty-two adult patients were treated with a CSCI of dexmedetomidine with a two-tier dose schedule, low and high dose. Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS, target <13), and sedation by the Richmond Agitation-Sedation Scale, Palliative Version (RASS-PAL, target −1 to −3). Results: All patients had a response to dexmedetomidine as measured by decrease in MDAS after initiation; 59% required escalation to high dose to maintain control of delirium. All responses to high dose were sustained. RASS-PAL scores showed significant variability, however mean scores remained within target range on both doses, and the majority of patients were rousable. Fifty percent of patients treated crossed over to standard care; no patients who crossed over were experiencing moderate-severe delirium. Predominant reason for crossover was family request for deeper sedation. Conclusion: Dexmedetomidine shows potential for the management of terminal delirium with improved interactivity. Further research is needed to determine efficacy compared to current standard care.

Dexmedetomidine: a magic bullet on its way into palliative care—a narrative review and practice recommendations

“…Therefore, dexmedetomidine treatment was initiated, starting on 0.2 µg/kg/h, but this needed to be titrated up to 0.7 µg/kg/h. This is of note, because the doses needed in the cases described by Kent and O'Hara are in and beyond the range of doses chosen for example by Thomas et al (50) for dexmedetomidine in palliative sedation. Mano et al (62) report a case of severe dyspnea treated with dexmedetomidine.…”

“…Inspired by the findings from the ICU setting and by promising results from earlier expert opinions (48) and case-reports from the field of palliative care (49), Thomas et al (50) published a prospective cohort study in endof-life patients with terminal hyperactive delirium. They included patients with hyperactive delirium of the terminal phase, where a causal approach was deemed inappropriate.…”

Efficacy and safety of subcutaneous clonidine for refractory symptoms in palliative medicine: a retrospective study

“…Sedation with phenobarbital was offered but she wished to remain alert. Aware that dexmedetomidine was reported to alleviate refractory symptoms in the hospice setting with less sedation than phenobarbital,1 2 we asked our intensive care unit colleagues for help. They suggested clonidine, an alternative α2 adrenoceptor agonist, because it has been widely used in critical care for pain and agitation since the 1990s 3 4.…”

Phenobarbital sedation via subcutaneous infusion in a palliative medicine unit: retrospective review

“…Hyperactive delirium at the end of life is distressing for both patients and families, with multiple agents used to relieve this distress, including benzodiazepines, phenothiazines as well as emerging use of alpha-2 agonists, for example, dexmedetomidine 3. Deeper sedation or refractory symptoms however necessitate stronger medication, with phenobarbital recommended for this 1.…”