DREAMS: Comparing dexmedetomidine versus midazolam at the end of life for sedative and anti-agitation effects

Patients near the end of life may suffer from an array of distressing symptoms, including pain, nausea, agitation, confusion and distress. Many patients will be delirious, with up to 88% of palliative care inpatients suffering a terminal delirium. When patients are distressed at the end of life, and other targeted symptomatic management has been unsuccessful, or when patients are struggling with confusion or distress, the treatment offered may be sedation, in order to relieve symptoms of anxiety, restlessness, emotional anguish and distress. Patients who require sedation at the end of life often appear comfortable to treating clinicians, but the loss of biographical life and interaction is often difficult and distressing to family and loved ones, and to patients themselves. Whilst comfort does appear to be maintained, the use of alternative sedation to allow meaningful biographical interaction with a patients loved ones could be considered desirable, especially if comfort could be preserved. Dexmedetomidine is an imidazole alpha-2 receptor agonist utilised commonly in the intensive care and anaesthetic environments. Dexmedetomidine was investigated in a clinical trial setting at the Port Kembla Palliative Care Unit (Joint University of Wollongong and Illawarra Shoalhaven Local Health District Human Research Ethics Committee (2018/247) as a potential therapeutic option for terminal delirium and rousable sedation, with results showing a trend to interactive sedation and decreased delirium. Standard care for distress at the end of life has typically involved benzodiazepine infusions, in Australia the most commonly utilised is midazolam. Despite this, the evidence base for benzodiazepine infusions at the end of life is not robust, with usage predominantly predicated on professional consensus and guidelines. Small-scale observational studies and retrospective analysis have been performed, but there is minimal evidence in the literature for actual efficacy trials, especially in patients treated with midazolam in the terminal phase of life. Given the gap in knowledge, the investigators propose a randomised controlled trial into the use of dexmedetomidine versus midazolam via continuous subcutaneous infusion (CSCI) in patients for sedation at the end of life. The subcutaneous (SC) route is chosen for this study as the preferred route of delivery as this conforms to the current standard of care for medication infusions given within the ISLHD for palliative care patients, and in NSW.