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

Abstract

Background and Objective: Dexmedetomidine is a potent adrenergic alpha-2 receptor agonist. It was first approved for sedation for mechanically ventilated patients. Being a sedative medication that is not associated with respiratory depression and holding analgesic properties fosters the interest for this drug in the palliative care field. The primary objectives of this review were to identify the key indications for the real-world use of dexmedetomidine in palliative care and other disciplines.Methods: A narrative review after extensive PubMed search was performed from 1950 to present on October 21st 2021. The language of the publications was restricted to English, German, French and Italian.Key Content and Findings: (I) Current dexmedetomidine use. There is a growing body of evidence that dexmedetomidine may reduce the incidence and severity of delirium, reduce opioid-consumption and postoperative nausea in intensive care settings. It is also used to facilitate withdrawal from different substances (alcohol, opioids, heroin). Concerning safety aspects of the drug, some studies reported an increased rate of serious cardiovascular events in patients with pre-existing heart conditions due to bradycardia and arterial hypo-and hypertension. Since the drug has a main hepatic metabolism, dose reduction is mandatory in patients with hepatic impairment. (II) Dexmedetomidine and palliative care. There have been sporadic case reports about the successful use of dexmedetomidine in palliative care. Indications for symptom control included sedation for hyperactive delirium, cancer pain, opioid-induced-hyperalgesia, dystonia, cough, vomiting, shivering and dyspnea. It is mainly applied via the intravenous (i.v.), subcutaneous, but also nasal and, buccal routes. Admixture ("syringe-driver") studies showed that dexmedetomidine is compatible with morphine, hydromorphone, hyoscine and haloperidol. In 2021, a first prospective cohort study became available. Here, the authors reported promising result for dexmedetomidine use in hyperactive terminal delirium for reducing delirium intensity and agitation. Especially the unique "conscious sedation"or "awake sedation" that allows patients to arouse easily under sedation and report comfort or distress was discussed by the authors. Conclusions:In this review, we present the main findings for dexmedetomidine from palliative care settings and other disciplines. The potential benefits and criticalities of the drug are discussed and practical recommendations for its use are provided.

Dexmedetomidine is a safe and useful palliative sedative for refractory dyspnoea in patients with terminal-stage cancer

“…In line with the dual goals of palliative care-to relieve distress and maintain close contact with family members when necessary-patients sedated with DEX can be roused by family members and medical staff to allow communication and reporting of their comfort level [29,30]. Although DEX does not provoke respiratory depression, clinicians should be aware that it may cause arrhythmias, including atrioventricular blocks, bradycardia, QT prolongation, arterial hypertension, and hypotension, when used for palliative sedation [31][32][33].…”

Dexmedetomidine ameliorates ischemia-induced nerve injury by up-regulating Sox11 expression

“…Furthermore, it might also be correlated with the development of cancer by influencing the hypoxia inducible factor (HIF) signaling and the PI3K/Akt pathway (14,15). Also, Dexmedetomidine is a promising agent for off-label use in palliative care (16). Therefore, it seems that Dex plays a vital role in cell survival and apoptosis, especially in the neuronal system.…”

The signaling and selectivity of α‐adrenoceptor agonists for the human α2A, α2B and α2C‐adrenoceptors and comparison with human α1 and β‐adrenoceptors

“… 16 , 18 , 19 It also has potential to help with delirium, agitation and induce sedation in the palliative care setting. 19 Furthermore, dexmedetomidine acts through endogenous sleep pathways, 20 mimicking natural sleep and has a unique window for inducing “arousal” or “cooperative” sedation, enabling neurosurgery to be undertaken in awake patients. 18 , 21 Clonidine and guanfacine are used in ADHD patients and avoid the hypertensive and cardiovascular risks of the traditional stimulants methylphenidate and amphetamine.…”

“…Dexmedetomidine is one of the most potent α2‐agonists to date 17 and is increasingly used in intensive care. It is used to sedate people requiring prolonged ventilation, induce short‐term sedation for procedures, as an adjunct to reduce doses of other sedatives (where a particular benefit is its lack of respiratory depression), reduce opiate consumption, reduce nausea and reduce delirium often seen post‐operatively and in intensive care patients 16,18,19 . It also has potential to help with delirium, agitation and induce sedation in the palliative care setting 19 .…”

“…It is used to sedate people requiring prolonged ventilation, induce short‐term sedation for procedures, as an adjunct to reduce doses of other sedatives (where a particular benefit is its lack of respiratory depression), reduce opiate consumption, reduce nausea and reduce delirium often seen post‐operatively and in intensive care patients 16,18,19 . It also has potential to help with delirium, agitation and induce sedation in the palliative care setting 19 . Furthermore, dexmedetomidine acts through endogenous sleep pathways, 20 mimicking natural sleep and has a unique window for inducing “arousal” or “cooperative” sedation, enabling neurosurgery to be undertaken in awake patients 18,21 .…”