Lessons from the Literature

2020; Volume 21, No 10, October

Under My Microscope

Dr. Tania Pastrana. Used with permission.

IAHPC Research Advisor Dr. Tania Pastrana selects one article from recently published medical literature and describes why it is worthwhile.

Neuroleptic Strategies for Terminal Agitation in Patients with Cancer and Delirium at an Acute Palliative Care Unit: A single-centre, double-blind, parallel-group, randomised trial

Hui D, De La Rosa A, Wilson A, Nguyen T, Wu J, et al. Lancet Oncol 2020; 21(7): 989-998. DOI: 10.1016/S1470-2045(20)30307-7

Delirium is a common symptom in palliative care that generates distress for the patient, caregivers, and health care personnel. Moreover, delirium is underdiagnosed and undertreated. The last update of the Cochrane Systematic Review at the beginning of 2020 “found low‐quality evidence that, compared to placebo, drug therapy (specifically haloperidol and risperidone) may slightly worsen delirium symptoms in terminally ill people with delirium of mild to moderate severity.”1

The research team, led by Dr. Eduardo Bruera of the M.D. Anderson Cancer Center in the United States, is contributing to much-needed evidence. The researchers’ aim was to evaluate the effect of three neuroleptic strategies on refractory agitation in cancer patients with terminal delirium who did not respond to low-dose haloperidol. They compared: 1) intravenous haloperidol, escalating 2 mg every 4 hours; 2) neuroleptic rotation chlorpromazine 25 mg every 4 hours; and 3) combined haloperidol 1 mg and chlorpromazine 12.5 mg every 4 hours. Participants were assessed every 30 minutes with the Richmond Agitation Sedation Scale.

The sample was collected during a two-year period (n=45). In all three patient groups, the RASS score decreased within 30 minutes of administration; few patients were deeply sedated. The researchers concluded that all three strategies using the high-dose neuroleptic reduced agitation in patients with refractory agitation at the end of life.

Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium.

Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486.

Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h −3·6 [95% CI −5·0 to −2·2]), rotation group (n=11, −3·3 [–4·4 to −2·2]), and combination group (n=10, −3·0 [–4·6 to −1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths.

Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group.

Funding: National Institute of Nursing Research


1. Finucane AM, Jones L, Leurent B, Sampson EL, Stone P, et al. Drug therapy for delirium in terminally ill adults. Cochrane Database of Systematic Reviews. Published online January 21, 2020. DOI: 10.1002/14651858.CD004770.pub3

Learn more about the M.D. Anderson Cancer Center in the Global Directory of Palliative Care Institutions and Organizations.

Do you have any questions regarding Under My Microscope?

Contact Tania Pastrana

Media Watch: Nursing

The articles below are selected from Barry R. Ashpole’s weekly report, Media Watch.

The Global Nursing Workforce: Realising universal palliative care

The Lancet: Global Health, 2020; 8(3): E327-E328. The authors identify how global healthcare systems can encourage the nursing workforce to implement the recommendations of the The Lancet Commission and WHO guidance on palliative care (PC). The skill set, experience, and perspectives of nurses are crucial to optimum PC policy development, strategic planning, service implementation, and research. WHO’s declaration of the International Year of the Nurse & Midwife makes 2020 the ideal time to promote nursing contributions to PC policy, training, and services in low-income and middle-income countries. DOI: 10.1016/S2214-109X(19)30554-6

Full text

See also: Phillips J, Johnston B, McIlfatrick S. Valuing palliative care nursing and extending the reach. Palliat Med2020; 34(2): 157-159.

Recommendations to Leverage the Palliative Nursing Role during COVID-19 and Future Public Health Crises

Journal of Hospice & Palliative Nursing | Online – 5 June 2020 – Palliative nurses (PN) will increasingly exercise their expertise in symptom management, ethics, communication, and end-of-life care. The literature addressing the palliative care response to COVID-19 has surged, and yet, there is a critical gap regarding the unique contributions of PN and their essential role in mitigating the sequelae of this crisis. The authors provide recommendations for PN to ensure their optimal value is realized and to promote their well-being and resilience during COVID-19. DOI: 10.1097/NJH.0000000000000665

Full text (click on pdf icon)

Protecting the Wellbeing of Nurses Providing End-of-Life Care

Nursing Times | Online – 13 January 2020 – A rise in the number of people who are dying in hospitals and hospices rather than at home is increasing the emotional labour of staff, particularly nurses. How do health professionals cope when tending for people who will die in their care? This article discusses issues around work-related stress in delivering high-quality patient care. It looks at what staff and organisations can do to manage stress and avoid burnout, particularly in caring for patients who are dying, including highlighting the role of the hospital chaplaincy as a resource for all staff.

Full text

See also: Simões AL. Thoughts of a palliative care nurse in times of pandemic. Patient Experience J; 7(2): article 9.

Human Touch via Touchscreen: Rural nurses’ experiential perspectives on telehealth use in pediatric hospice care

Journal of Pain & Symptom Management | Online – 7 June 2020 – The deeper concern with telemedicine use in palliative and hospice care is the concern with whether this communication modality is a facilitator or a barrier for the relationality so core to the nursing profession. Palliative and hospice teams have shared concerns about the way telehealth impacts professional roles: telehealth’s impact to professional autonomy, fear of decay in the quality of care provided, and concern for risk of not being present to assist the patient such as in adverse medication reactions. DOI: 10.1016/j.jpainsymman.2020.06.003

Full text

Media Watch monitors the literature and the lay press on issues specific to the quality of end-of-life care. It is international in scope and distribution. View current and back issues here.

Previous Page News Index Next Page


This newsletter, including (but not limited to) all written material, images, photos are protected under international copyright laws and are property of the IAHPC. You may share the IAHPC newsletter preserving the original design, the IAHPC logo, and the link to the IAHPC website, but you are not allowed to reproduce, modify, or republish any material without prior written permission from the IAHPC.