Lessons from the Literature

Volume 23, Number 3: March 2022

Under My Microscope

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

Dr. Tania Pastrana. Used with permission.

By Dr. Tania Pastrana
IAHPC Research Advisor

Effect of Continuous Deep Sedation on Survival in the Last Days of Life of Cancer Patients: A multicenter prospective cohort study

Yokomichi N, Yamaguchi T, Maeda I, Mori M, Imai K, Shirado Naito A, Yamaguchi T, Terabayashi T, Hiratsuka Y, Hisanaga T, Morita T. Palliat Med 2002; 36(1): 189-199. DOI: 10.1177/02692163211057754

At the end of the life, symptoms such as delirium, agitation, anxiety, terminal restlessness, dyspnea, pain, vomiting, and psychological and physical distress may became difficult to manage with the current pharmaceutical options. This situation causes distress to the patient, their family, and the health care team. The reduction in patient consciousness through continuous deep sedation is a helpful option in cases of refractory symptoms. However, there are concerns that its use may shorten the patient’s survival.

Until now, systematic reviews have not reported this effect, but those reviews have been based on studies with low evidence level (retrospective, case-controlled or case studies): there are few prospective, nonrandomized studies.

Naosuke Yokomichi and colleagues conducted the first multicenter prospective cohort study “to examine whether continuous deep sedation is associated with patient survival in the last days of life using patient data from a multicentre prospective cohort study.” By continuous deep sedation, the authors mean the continuous administration of sedative medication [mostly midazolam] with the intention of keeping a patient continuously unconscious to alleviate otherwise uncontrollable symptoms [RASS ⩽ −4], according to their national guideline.

They analyzed data from 1,625 patients with advanced cancer from 23 palliative care units that are part of the East-Asian collaborative cross-cultural Study to Elucidate the Dying process (EASED) group.

They concluded that “continuous deep sedation with careful dose adjustment was not associated with shorter survival in patients with advanced cancer, and continuous deep sedation had no measurable effects on survival.” However, the authors recommend continuing to study the issue.

Link to article

Background: Continuous deep sedation is ethically controversial with respect to whether it shortens a patient's life.

Aim: To examine whether continuous deep sedation shortens patient survival from the day of Palliative Performance Scale decline to 20 (PPS20).

Design: A part of a multicenter prospective cohort study (EASED study).

Setting/participants: We recruited consecutive adult patients with advanced cancer admitted to 23 participating palliative care units in 2017 in Japan. We compared survival from PPS20 between those who did and did not receive continuous deep sedation. Continuous deep sedation was defined as the continuous administration of sedative medication with the intention to keep a patient continuously unconscious to alleviate otherwise uncontrollable symptoms, but the dose of sedatives was adjusted to achieve adequate symptom relief for each patient. The propensity score-weighting method was used to control for potential confounders, and five sensitivity analyses were performed.

Results: A total of 1926 patients were enrolled. Patients discharged alive were excluded, and we analyzed 1625 patients of whom 156 (9.6%) received continuous deep sedation. Median survival from PPS20 of 1625 patients was 81 h (95% CI: 77-88). The RASS scores decreased to ⩽-4 was 66% at 24 h. Continuous deep sedation was not associated with a significant survival risk (adjusted hazard ratio: 1.06, 95% CI: 0.85-1.33). All sensitivity analyses, including continuous deep sedation defined as the RASS score was ⩽-4 achieved the essentially the same results.

Conclusions: Continuous deep sedation with careful dose adjustment was not associated with shorter survival in the last days of life in patients with advanced cancer.


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Media Watch

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

Experiences and Attitudes of Medical Professionals on Treatment of End-of-Life Patients in Intensive Care Units in the Republic of Croatia: A cross-sectional study

BMC Medical Ethics | Online – 16 February 2022 – This is the first study to assess the experiences and attitudes of medical professionals working in intensive care units in Croatia on the treatment of end-of-life patients. Withdrawing life-saving treatments (LSTs) was ethically acceptable for 64% of participants, and 79% said that decisions of capable patients about LST should be respected. However, DNACPR (do not attempt cardiopulmonary resuscitation) orders are not commonly made in Croatian ICUs. This may be due to a discrepancy between what ICU medical professionals witness daily and what is allowed by law. Croatia is a mainly Catholic country and paternalistic and conservative attitudes are expected considering its geographical location in Southern Europe, as found by previous studies.

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Nordic Specialist Course in Palliative Medicine: Evaluation and impact on the development of palliative medicine in the Nordic countries: A survey among participants from seven courses 2003–2017

Journal of Palliative Medicine 2021; 24(12): 1858-1862. This article describes the successful experience of establishing and running a common palliative medicine (PM) specialist training course involving five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Survey results and registry data demonstrate the course’s profound impact on participants' post-course careers. Most former participants are now working within PM as leaders and teachers and are actively promoting the development of PC in their respective countries. The course has been instrumental in getting PM approved as a formal competence field in Finland, Norway, and Denmark, and an add-on specialty in Sweden and Iceland.

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Related: Lessons Learned from Introducing Last Aid Courses at a University Hospital in Germany

Early Palliative Care Associated with Lower Costs for Adults with Advanced Cancer: Evidence from Hungary

European Journal of Cancer Care 2021; 30(6): e13473. This study demonstrated that early palliative care (PC) for end-stage cancer patients with a very limited prognosis can add value to healthcare by reducing unnecessary costs associated with hospital stays and useless examinations and treatments. Facilitating increased use of home care in Hungary is economically rational and policymakers should investigate how this form of care could be developed (also considering the burden placed on family members, informal caregivers. Awareness of PC needs to be increased in order to achieve earlier patient involvement in this form of care.

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Also of interest:


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.


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