Frequency of euthanasia, factors associated with end-of-life practices, and quality of end-of-life care in patients with amyotrophic lateral sclerosis in the Netherlands: a population-based cohort study

Background Amyotrophic lateral sclerosis is a progressive and lethal neurodegenerative disease that is at the forefront of debates on regulation of assisted dying. Since 2002, when euthanasia was legally regulated in the Netherlands, the frequency of this end-of-life practice has increased substantially from 1 center dot 7% of all deaths in 1990 and 2005 to 4 center dot 5% in 2015. We aimed to investigate whether the frequency of euthanasia in patients with amyotrophic lateral sclerosis had similarly increased since 2002, and to assess the factors associated with end-of-life practices and the quality of end-of-life care in patients with this disease. Methods Using data from the Netherlands ALS registry, we did a population-based cohort study of clinicians and informal caregivers of patients with amyotrophic lateral sclerosis to assess factors associated with end-of-life decision making and the quality of end-of-life care. We included individuals who were diagnosed with amyotrophic lateral sclerosis according to the revised El-Escorial criteria, and who died between Jan 1, 2014, and Dec 31, 2016. We calculated the frequency of euthanasia in patients with amyotrophic lateral sclerosis from reports made to euthanasia review committees (ERCs) between 2012 and 2020. Results were compared with clinic-based survey studies conducted in 1994-2005. End-of-life practices were end-of-life decisions by a clinician when hastening of death was considered as the potential, probable, or definite effect comprising euthanasia, physician-assisted suicide, ending of life without explicit request, forgoing life-prolonging treatment, and intensified alleviation of symptoms. Findings Between Jan 1, 2012, and Dec 31, 2020, 4130 reports of death from amyotrophic lateral sclerosis were made to ERCs, of which 1014 were from euthanasia or physician-assisted suicide (mean frequency 25% [SD 3] per year). Sex and gender data were unavailable from the ERC registry. Of 884 patients with amyotrophic lateral sclerosis who died between Jan 1, 2014, and Dec 31, 2016, their treating clinician was identified for 731 and a caregiver was identified for 741, of whom 356 (49%) and 450 (61%), respectively, agreed to participate in the population-based survey study. According to clinicians, end-of-life practices were chosen by 280 (79%) of 356 patients with amyotrophic lateral sclerosis who died. The frequency of euthanasia in patients with amyotrophic lateral sclerosis in 2014-16 (141 [40%] of 356 deaths in patients with amyotrophic lateral sclerosis) was higher than in 1994-98 (35 [17%] of 203) and 2000-05 (33 [16%] of 209). Median survival of patients with amyotrophic lateral sclerosis from diagnosis was 15 center dot 9 months (95% CI 12 center dot 6-17 center dot 6) for those who chose euthanasia and 16 center dot 1 months (13 center dot 4-19 center dot 1) for those who did not choose euthanasia (hazard ratio 1 center dot 07, 95% CI 0 center dot 85-1 center dot 34; p=0 center dot 58). According to caregivers, compared with other end-of-life practices, patients with amyotrophic lateral sclerosis choosing euthanasia commonly reported reasons to hasten death as no chance of improvement (53 [56%] of 94 patients who chose euthanasia vs 28 [39%] of 72 patients who chose other end-of-life practices), loss of dignity (47 [50%] vs 15 [21%]), dependency (34 [36%] vs five [7%]), and fatigue or extreme weakness (41 [44%] vs 14 [20%]). According to caregivers, people with amyotrophic lateral sclerosis-whether they chose euthanasia or did not-were satisfied with the general quality (83 [93%] of 89 patients who chose euthanasia vs 73 [86%] of 85 patients who did not) and availability (85 [97%] of 88 vs 81 [91%] of 90) of end-of-life care. Interpretation The proportion of patients with amyotrophic lateral sclerosis who chose euthanasia in the Netherlands has increased since 2002. The choice of euthanasia was not associated with disease or patient characteristics, depression or hopelessness, or the availability or quality of end-of-life care. The choice of euthanasia had no effect on overall survival. Future studies could focus on the effect of discussing end-of-life options on quality of life as part of multidisciplinary care throughout the course of the disease, to reduce feelings of loss of autonomy and dignity in patients living with amyotrophic lateral sclerosis.