Continuous Deep Sedation is Not Associated with Shorter Survival in the Last Days of Life in Patients with Advanced Cancer: A Propensity Score-Weighted Analysis of a Prospective Cohort Study

Abstract

Background: Continuous deep sedation (CDS) is ethically controversial with respect to whether it shortens a patient’s life. Previous studies reported no significant difference in survival from admission or enrolment into a palliative care program to death between patients treated with and without CDS. However, these baselines are too distant from the initiation of CDS to detect the effect of CDS on survival. We aimed to examine whether CDS shortens patient survival from the day of Palliative Performance Scale decline to 20 (PPS20). Methods: This study was a part of a multicenter prospective cohort study that recruited patients between Jan. and Dec. 2017 in Japan (EASED study). Consecutive Adult patients with advanced cancer admitted to 23 participating inpatient palliative care units were eligible for this analysis. We compared survival from PPS20 between those who did and did not receive CDS. We used the inverse probability of treatment weighting method to control for potential confounders of patient characteristics, complications and laboratory data at admission, and symptoms at PPS20. Findings: A total of 1926 patients were enrolled. Of these, patients discharged alive were excluded, and finally we analyzed 1625 patients of whom 156 (9.6%) received CDS. Median survival from PPS20 of 1625 patients was 3.4 days (95% CI: 3.2-3.7). CDS was not associated with a significant survival risk from PPS20 (adjusted hazard ratio: 1.06, 95% CI:0.85–1.33; p = 0.595). In exploratory subgroup analyses, a significant survival risk was not observed in any subgroup except for those with primary lung cancer and agitated delirium. Interpretation: CDS was not associated with shorter survival in the last days of life in patients with advanced cancer, and CDS had no measurable effects on survival. Our findings may relieve the concern of patients, families, and physicians that CDS might shorten survival. Funding Statement: This work was supported by Grant-in-Aid from the Japanese Hospice Palliative Care Foundation and in part by JSPS KAKENHI Grant number JP19H03869. Declaration of Interests: No relevant conflict of interest to declare. Ethics Approval Statement: This study was conducted in accordance with the ethical standards of the Helsinki Declaration and the ethical guidelines for epidemiologic research of the Ministry of Health, Labour and Welfare of Japan. The local institutional review boards of all participating institutions approved this study. Japanese law does not require individual informed consent from participants in a non-invasive observational trial such as this. Therefore, we used an opt-out method rather than acquiring written or oral informed consent.