Effect of continuous deep sedation on survival in the last days of life of cancer patients: A multicenter prospective cohort study

Abstract

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.

Continuous palliative sedation in terminally ill patients with cancer: a retrospective observational cohort study from a Chinese palliative care unit

“…It is more scientific and reasonable to evaluate the survival time at the same level. Yokomichi e et al 18 used the patient’s Palliative Performance Scale down to 20 to measure the impact of continued sedation on patient survival. This is a method worth learning for us; in the future, we can explore this in some prospective studies.…”

“…Moreover, many empirical studies showed that palliative sedation has no adverse effect and may even prolong survival time in patients with advanced cancer. [14][15][16][17][18] However, most studies focused on areas with mature palliative care development, whereas only a few relevant studies focused on developing areas of palliative care. It is well-known that many factors, such as country, culture, subjects and local nursing environment, affect palliative sedation.…”

“…Van Deijck et al 13 reported patient-related determinants during palliative sedation. Moreover, many empirical studies showed that palliative sedation has no adverse effect and may even prolong survival time in patients with advanced cancer 14–18. However, most studies focused on areas with mature palliative care development, whereas only a few relevant studies focused on developing areas of palliative care.…”

Palliative Sedation in End-of-Life Patients in Eastern Asia: A Narrative Review

“…A large-scale study in Japan showed no significant differences in the average survival period between a group of 269 patients given continuous sedation and a group of 1,558 patients who were observed but not given sedation (27 days vs. 26 days) [ 12 ]. A recent large cohort prospective study in Japan revealed that there was no detrimental effect of continuous deep PS on survival in the last days of life of cancer patients (adjusted hazard ratio, 1.06; 95% confidence interval, 0.85 to 1.33) [ 13 ]. Another study in Western countries also reported that no significant difference existed in the average survival time between a group of 502 patients with continuous PS and a group of 1,912 patients without PS (10 days vs. 9 days) [ 14 ].…”

Response to Morita et al., Re: Defining “Continuous Deep Sedation” Using Treatment Protocol (DOI: 10.1089/pmr.2021.0058)

“…In Japan, the estimated prognosis of patients requiring CDS typically seems to be only a few days. 2 , 3 This suggests that the typical clinical context for CDS in Japan could be different from, for example, that in The Netherlands, even though guidelines in both countries permit CDS in patients with an estimated prognosis of less than or equal to two weeks. Thus, for comparative purposes, it is essential for any treatment protocol used for monitoring and research purposes to record the physical status of the patients when CDS is started, and the time until death.…”