Greg Barclay

Objectives: Patients in the terminal phase may require both regular medications and breakthrough medications for palliative symptom management. Breakthrough dosing can provide an objective measure of symptom management, but the relationships between symptom severity and breakthrough use in sedated patients in the terminal phase remain unclear. This study examined the relationship between symptom management and breakthrough medication use in dying patients receiving dexmedetomidine or midazolam as background sedative infusions. Methods: This secondary analysis of the Dexmedetomidine for the Relief of End-of-life Agitation and optiMised Sedation trial included 52 palliative care inpatients randomised to subcutaneous infusion of dexmedetomidine (0.5 µg/kg/hour) or midazolam (0.25 mg/kg/day). Breakthrough medication use was correlated with Palliative Care Problem Severity Score (PCPSS) scores (0–3) using Spearman’s coefficient. Primary analyses matched PCPSS-Pain with opioids, PCPSS-Psychological/Spiritual with sedatives and PCPSS-Other with other breakthrough medications, applying a Bonferroni correction (α=0.0083). Results: In total, 130 patient-days were analysed (71 dexmedetomidine, 59 midazolam). Symptom severity was mild and equivalent between arms (median PCPSS scores 0–1, all p>0.05). Total breakthrough doses were similar (2.5–3 daily). In the dexmedetomidine arm, PCPSS-Pain correlated with opioid use (r=0.46, p=0.001) and PCPSS-Psychological/Spiritual with sedative use (r=0.49, p=0.003), with a nonsignificant trend for PCPSS-Other (r=0.21, p=0.17). In the midazolam arm, correlations were absent or negative (r=−0.24 to 0.068, p>0.05). Conclusions: Dexmedetomidine patients showed significant correlations between symptom severity and breakthrough opioid or sedative use, whereas midazolam patients did not. Despite similar mild symptom scores and breakthrough needs, only dexmedetomidine demonstrated expected symptom-medication relationships. This divergence warrants further research.

Background: Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing. Objective: The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation. Methods: Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale–Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale–Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care. Results: The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026. Conclusions: The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones. Trial Registration: Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889 International Registered Report Identifier (IRRID): DERR1-10.2196/55129

Background: Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature to guide practice is limited. Case reports have documented standard doses of opioids and benzodiazepines used for sedation in such cases. Case: A 49-year-old man was diagnosed with motor neurone disease in 2016. He commenced tracheostomy ventilation in 2018. In 2022 and 2023, planning was undertaken, at the patient’s request, for withdrawal of tracheostomy ventilation at home, when he was no longer able to communicate with technology. Case planning: Planning included Bispectral Index monitoring prior to cessation of ventilation, ensuring this only occurred when deep sedation was achieved. After ventilation withdrawal in 2023, a retrospective review of medications given and his level of sedation on monitoring was undertaken, with family consent. Outcome: Ventilation withdrawal was initiated after deep sedation was achieved, 6 h after commencing subcutaneous infusions of morphine, midazolam, clonazepam and phenobarbital. Lessons: Doses required to achieve acceptable sedation exceeded literature reports. Achieving deep sedation was a longer than expected process. Conclusion: More research using an objective measure of sedation is required, as clinical assessment of sedation in this context is compromised.

BACKGROUND Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing. OBJECTIVE The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation. METHODS Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale–Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale–Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care. RESULTS The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026. CONCLUSIONS The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones. CLINICALTRIAL Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/55129

Objective: The aim of this study was to assess the unmet need for palliative and other end-of-life care, as well as the sociodemographic and diagnostic factors associated with suboptimal access, among residents in an Australian region. Methods: A cross-sectional descriptive and analytical study was performed using non-identifiable linked data from four administrative and two clinical datasets. The study population comprised 3175 patients aged =15 years who died in hospital in 2016 and 2017. The main outcome measures were the proportion of decedents potentially benefitting from end-of-life care and receiving end-of-life care. Results: An estimated 74.8% of decedents needed palliative or other end-of-life care in the year before death. Approximately 13.3% did not receive any end-of-life care despite its potential benefit. The highest proportions with ‘unmet need’ were decedents with chronic obstructive pulmonary disease (31.0%) and heart failure (26.3%). Adjusting for sociodemographic and diagnostic factors, access was lowest among those aged <65 years (adjusted odds ratio (aOR) 0.44; 95% confidence interval (CI) 0.31–0.64) and those with heart failure (aOR 0.58; 95% CI 0.47–0.72). Conclusions: Estimates of need and access provide a sound basis for planning local palliative and end-of-life care services. These methods can be used on an ongoing basis to monitor service delivery. What is known about this topic?: There is a small but expanding literature on estimating the need for palliative care at a population level. There is a lack of data regarding access to palliative and other end-of-life care across multiple settings (e.g. home, specialist palliative care unit, hospital) and patient groups (e.g. defined by sociodemographics and diagnostics). What does this paper add?: The study builds on previously used methods for estimating the need for palliative care, with some refinements, including the addition of ‘other clinical indications’ and the use of weights to derive more realistic estimates. The estimates of need are consistent with recent estimates from Australia and overseas, whereas the estimates of access are similar to a recent Australian estimate, but higher than estimates from overseas. The gaps in access are highest among those with the major types of chronic organ failure, particularly heart and respiratory. What are the implications for practitioners?: The study demonstrates how routinely collected data at a regional level can be used to estimate need and access to palliative and end-of-life care, in the hospital and in the community. These methods of estimating need and unmet need can be used to inform the planning and development of services, as well as to monitor progress with implementation of changes in service provision.