Background: How often does refractory suffering, which is suffering due to symptoms that cannot be adequately controlled, occur at the end of life in modern palliative care? What are the causes of such refractory suffering? Should euthanasia be offered for refractory suffering at the end of life? We sought to shed light on these questions through interviews with palliative care specialists.
Methods: Semi-structured interviews with six nurses and six doctors working in palliative care in five Norwegian hospitals. Transcripts were analysed with systematic text condensation, a qualitative analysis framework.
Results: Informants find that refractory suffering is rare, and that with palliative sedation satisfactory symptom control can nearly always be achieved at the end of life. However, the process of reaching adequate symptom control can be protracted, and there can be significant suffering in the meantime. Both somatic, psychological, social and existential factors can contribute to refractory suffering and potentiate each other. However, informants also place significant weight on factors pertaining to the organization of palliative care services as contributing to insufficient symptom control.
Conclusions: If refractory suffering is indeed rare, then this arguably weakens a common prima facie argument for the legalization of assisted dying. However, the process of reaching adequate symptom control can be protracted and involve significant suffering. The experiences of palliative care clinicians constitute important empirical premises for the assisted dying debate. The study points to several areas in which palliative care can be improved.
Background: pain is a common symptom of head and neck cancers. In some instances, pain may not resolve with conventional modalities and become refractory. Chemical neurolysis is a technique that utilizes chemical neurolytic agents to temporarily denervate a targeted nerve and provide relief in pain-related symptoms. The aim of this investigation was to determine the effectiveness, safety, and predictors of chemical neurolysis procedures for management of refractory head and neck cancer-related pain.
Methods: A retrospective chart review of patients who underwent chemical neurolysis procedure in the regions of head and neck for management of head and neck cancer-related pain was conducted between November 2017 and November 2018. All adult male and female patients who had undergone chemical neurolysis procedure in the head and neck region for management of refractory head and neck related pain, in Orofacial Pain Clinic, Shaukat Khanum Memorial Cancer Hospital and Research Center were included in the investigation.
Results: Among 33 participants enrolled, 72.7% of participants experienced 75% or greater relief in pain at the 1-month follow-up. However, 9.1% reported experiencing an adverse effect following neurolysis. A statistically significant association was found between neurolysis effectiveness and chronicity of pain.
Conclusions: Chemical neurolysis can provide significant relief to patients with refractory head and neck cancer-related pain as an adjunctive therapy. However, it was found to be associated with mild risk of manageable adverse effects. Shorter chronicity of pain was found to be associated with successful outcome.
Introduction : En France, la méthadone est autorisée uniquement comme traitement de substitution. Elle peut être utilisée pour les douleurs liées au cancer. Le but de cette étude est d’évaluer l’efficacité et les effets secondaires de la méthadone dans cette indication.
Méthode : Il s’agit d’une étude rétrospective de janvier 2010 à février 2011, incluant tous les patients recevant de la méthadone pour la première fois. Le soulagement était considéré comme obtenu si l’intensité de la douleur était inférieure ou égale à 3/10 sur l’échelle d’évaluation numérique (EN) ou inférieure ou égale à 30/100 sur une échelle visuelle analogique (Eva), à j7 et j28. Les effets secondaires et leur persistance ont été explorés pendant l’instauration, à j7 et j28.
Résultats : Vingt-deux patients ont été inclus. Vingt patients ont été évalués au 7e jour, dix-huit patients à 28e. À j7, seize patients (80 %) étaient soulagés et onze (61 %) au 28e jour. Peu de patients ont présenté des effets indésirables : 8 patients (40 %) à j7 et 3 (16,7 %) à j28.
Conclusion : La méthadone est un traitement utile contre la douleur cancéreuse, en particulier pour la douleur cancéreuse rebelle et complexe.
Background: Uncontrolled cancer pain is a significant problem in palliative medicine. Opioids are often first-line treatment that increase risks of analgesic tolerance and hyperalgesia. Topical ketamine with other adjuvant pain medications is an often-overlooked treatment, yet may be most effective in difficult-to-treat cancer pain.
Objective: We report a case series of hospice patients with uncontrolled cancer pain who were suboptimally treated with opioids and nerve blocks, whose symptoms responded to topical ketamine with other adjuvants. We review the pronociceptive properties of opioids and how topical multimodal treatment of cancer pain can be more effective than standard opioids, other topical adjuvant medications, and nerve blocks. We discuss the shortcomings of the World Health Organization (WHO) stepladder for the treatment of cancer pain and suggest an adjuvant treatment algorithm, directing physicians to appropriate adjuvant pain agents based on pain type and distinct receptor actions.
Design: This is a retrospective case series of patients who responded to topical multimodal pain treatment with implementation of findings into an addendum to the WHO stepladder.
Subjects: Subjects were from a case series of community-based hospice patients with previously uncontrolled cancer pain.
Measurement: Measurement was made by self-report of pain levels using the 10-point numeric pain rating scale.
Results: Patients' pain was controlled with topical adjuvant medications with return to previously lost function and prevention of otherwise escalating opioid dosing.
Conclusions: These patient cases reveal how ketamine-based topical treatment for cancer pain can be more effective than standard opioids, other topical adjuvant medications, and nerve blocks with no noted side effects and observed reduction in opioid consumption.
Pain in people with advanced cancer is prevalent. When a stable dose of opioids is established, people still experience episodic breakthrough pain for which dosing of an immediate release opioid is usually a proportion of the total daily dose. This multi-site, double blind, randomised trial tested three dose proportions (1/6, 1/8, 1/12 of total daily dose) in two blocks, each block with three dose proportions in random order (6 numbered bottles in total). When participants required opioid breakthrough doses and it was their first breakthrough dose for that study day, they took the next numbered bottle rather than their usual breakthrough dose. (Subsequent doses on that day reverted to their usual dose.) Eighty five people were randomised in this study of whom 81 took at least one dose and 73 (90%) took at least block one (one of each dose proportion). No dose was found to be optimal at 30 min with approximately one third of participants showing maximal reduction with each dose proportion. Median time to pain relief was 120 min. There were no differences in harms: drowsiness, confusion, nausea or vomiting at 30, 60 or 120 min. This adequately powered study did not show any difference with three dose proportions for reduction in pain intensity, time to pain relief, pain control on the subsequent day nor any difference in harms. From first principles, this suggests 1/12 the 24 hourly dose should be used as the lowest dose that delivers benefit. Future studies should include a placebo arm.
As patients approach the end of life, they often experience a range of distressing symptoms and concerns such as pain, delirium, and breathlessness. Although most symptoms and concerns are amendable to pharmacological and/or nonpharmacological interventions, there may be some symptoms that are very difficult or impossible to treat or where available treatment options fail. These are called refractory symptoms because treatment (1) does not work, (2) the effects take too long to happen, or (3) the side effects are not acceptable to the patient. Refractory symptoms are not restricted to physical symptoms and, therefore, a multidimensional approach is needed to fully assess and manage the patient's condition. For example, existential suffering may be adding to the patient's physical suffering but can be particularly difficult to assess and manage. For this reason, the term intractable suffering is sometimes used. When conventional treatment options are no longer available and symptoms are considered refractory, the option of palliative sedation comes to the fore.
Ces recommandations de la Haute Autorité de Santé ont pour objectifs de mieux définir les modalités d'utilisation des traitements médicamenteux, en particulier hors AMM, en situation palliative et phase terminale chez l'adulte :
- pour l'antalgie des douleurs rebelles ou la prévention des douleurs rebelles provoquées ;
- pour la sédation, qu'elle soit proportionnée ou profonde et continue maintenue jusqu'au décès ;
- y compris, le cas échéant, les modalités spécifiques au domicile.
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But de l'étude : évaluer l'efficacité analgésique de l'injection de morphiniques par une chambre à cathéter implantable intrathécal pour les douleurs cancéreuses réfractaires.
Type d'étude : étude prospective expérimentale, mono centrique.
Matériel et méthode : nous avons inclus tous les patients de plus de 18 ans vus en consultation douleur, de mars 2015 à juin 2018 qui présentaient une douleur chronique d'origine cancéreuse. Ceux qui présentaient une contre-indication à la technique ou une injection-test non efficace non pas été inclus. Mise en place du cathéter intrathécal lombaire et administration de la morphine dont la posologie est fonction du résultat obtenu lors de l'injection-test. Les critères de jugements principaux sont : l'évaluation de l'intensité de la douleur par l'échelle visuelle analogique, et la qualité de vie des malades. L'analyse statistique a utilisé le logiciel Statistical Package for the Social Sciences.
Résultats : 61 patients étaient inclus dans l'étude, mais seulement 24 patients ont bénéficié d'un site implantable intrathécal. L'âge moyen à l'instauration de l'analgésie était de 55,45 ans plus ou moins 7,12 années. Le délai entre le diagnostic et l'implantation était de 3,61 ans en moyenne. La localisation du cancer primitif est essentiellement génito-urinaire et digestif, et la localisation des douleurs est essentiellement pelvi-péritonéale. On note que la douleur a chuté de 54,58 %, avec une nette amélioration de la qualité de vie. Un cas de fuite du liquide céphalorachidien, une infection locale au point de ponction, et un cas d'infection de la loge, qui ont répondu au traitement.
Conclusion : au terme de cette analyse, il fau bien reconnaître que l'analgésie intrathécale procure une analgésie de très bonne qualité, mais il existe une proportion non négligeable de complications, pour cela elle n'est proposée qu'aux patients qu'en dernier recours.
Background: Ketamine has been used as an adjuvant to opioid therapy for the management of refractory cancer pain but the current evidence is insufficient to draw any conclusions regarding its efficacy. We aimed to assess the response to ketamine in patients with refractory cancer pain treated in an oncology palliative care unit.
Methods: Patients with refractory cancer pain despite opioid dose escalation were selected for a trial of parenteral ketamine infusion according to a local protocol. The medical records of those patients treated between January 2004 and December 2018 were retrospectively reviewed. The primary endpoint of the study was a favorable response to ketamine, defined as a reduction in regular opioid dose with no increase in pain intensity or a reduction in pain intensity by =2 points on the numerical rating scale (NRS) with a stable regular opioid dose. The secondary endpoint was adverse events associated with ketamine.
Results: Among the 70 patients, mean pain score on NRS improved from 7.0 to 4.0 after ketamine (P<0.001). Forty-nine patients had a reduction of pain score by =2 points on NRS, 33 had =50% reduction in pain intensity. The median decrease in regular opioid dose was 25.5%, and the mean difference was -133.2 mg (P=0.002). A favorable response to ketamine was observed in 52 patients (74.3%). The use of more than one coanalgesic (odds ratio 3.451; 95% CI: 1.087–10.960; P=0.036) was associated with a favorable response to ketamine on multivariate analysis. Adverse events were mostly mild, with the commonest being drowsiness (45.7%), hypertension (34.3%) and nightmares (25.7%). Only five and three patients required temporary suspension and early termination of ketamine infusion respectively.
Conclusions: These data demonstrated the efficacy and safety of ketamine in a population of patients with refractory cancer pain. The use of more than one coanalgesic was associated with a favorable response to ketamine. Further large and multicentered studies are warranted to confirm these data.
Background: This case report describes a patient with known idiopathic Parkinson’s disease, being managed with transdermal rotigotine, whose refractory nausea and vomiting was successfully controlled with subcutaneous levomepromazine. No drug-induced extrapyramidal side effects emerged.
Case presentation: A patient was found to have a locally advanced serous carcinoma, causing secondary bowel obstruction. Furthermore, due to compromised oral access, the patient’s oral antiparkinsonian medications for motor control were converted to transdermal rotigotine. Unfortunately, the patient’s nausea and vomiting was refractory to a number of recommended antiemetic options.
Case management: Low dose levomepromazine was administered on a, ‘when required’ basis, via subcutaneous injection.
Case outcome: After the first dose of levomepromazine, the patient’s nausea and vomiting completely subsided and no extrapyramidal side effects were observed. This was confirmed by daily assessments, revealing no worsening of the motor symptoms associated with idiopathic Parkinson’s disease.
Conclusions: The pharmacology of rotigotine and levomepromazine appear complementary and may allow for the simultaneous use of both drugs, with favourable outcomes. This case report highlights that rotigotine may afford protection against antipsychotic induced extrapyramidal side effects, while preserving antiemetic effects. Such combinations may have a role in the end-of-life management of idiopathic Parkinson’s disease.
Limited data exist describing the outcomes of patients receiving continuous lidocaine infusions. The objective of this study was to evaluate the effect of use of continuous lidocaine infusions for pain management at a community teaching hospital. A retrospective chart review was performed that included adult patients receiving continuous systemic lidocaine infusions for the treatment of pain. Twenty-one patients were included in the analysis. Dosing ranged from 0.25 to 2.8 mg/kg/h, with a median infusion time of 64 hours. Eight patients (38%) experienced a response (≥20% reduction in pain score during the infusion compared with prior to the infusion). Among responding patients, there was a decrease in pain scores at rest after starting lidocaine (compared with prior to lidocaine) (6.5 vs. 3.7, P = .001) that was maintained 24 hours after lidocaine discontinuation. There were no differences in pain scores before, during, or after lidocaine in the entire study sample. A difference in oral morphine equivalent intake was present comparing usage during the infusion vs. day +1 (P = .006) and day +2 (P < .001). Similarly, a difference was present comparing morphine equivalent usage on day −2 with day +2 (P = .008) and day −1 with day +1 (P = .006). Continuous infusions of systemic lidocaine appear to be beneficial in some patients experiencing uncontrolled pain and may improve pain scores while decreasing opioid requirements. Overall beneficial effects of systemic lidocaine may last longer than the infusion itself.
CONTEXT: Fear of pain resonates with most people, in particular in relation to dying. Despite this, there are still people dying with unrelieved pain.
OBJECTIVES: We quantified the risk, and investigated risk factors, for dying with unrelieved pain in a nationwide observational cohort study.
METHODS: Using data from Swedish Register of Palliative Care we analysed 161 762 expected deaths during 2011-2015. The investigated risk factors included cause of death, place of death, absence of an end-of-life (EoL) conversation, and lack of contact with pain management expertise. Modified Poisson regression models were fitted to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for unrelieved pain.
RESULTS: Unrelieved pain during the final week of life was reported for 25% of the patients with pain, despite prescription of opioids PRN in 97% of cases. Unrelieved pain was common both among patients dying from cancer and from non-malignant chronic diseases. Significant risk factors for unrelieved pain included hospital death (RR = 1.84, 95% CI 1.79-1.88) compared with dying in specialist palliative care, absence of an EoL conversation (RR = 1.42, 95% CI 1.38-1.45), and dying from cancer in the bones (RR = 1.13, 95% CI 1.08-1.18) or lung (RR = 1.10, 95% CI 1.06-1.13) compared with non-malignant causes.
CONCLUSION: Despite almost complete prescription of opioids PRN for patients with pain, patients die with unrelieved pain. Health care providers, hospitals in particular, need to focus more on pain in dying patients. An EoL conversation is one achievable intervention.
Purpose. This study aimed to characterize breakthrough pain (BTP) and investigate its impact on quality-of-life (QoL) in terminally-ill cancer patients. Similarities and differences between high and low predictable BTP were also tested. Methods. Secondary analysis of a multicenter longitudinal observational study included 92 patients at their end-of-life. BTP was assessed with a short form of the Italian version of the Alberta Breakthrough Pain Assessment Tool. QoL was assessed with the Palliative Outcome Scale (0-40). Patients were stratified by self-reported BTP predictability into unpredictable BTP (never or rarely able to predict BTP) and predictable BTP (sometimes to always able to predict BTP). Results. In all, 665 BTP episodes were recorded (median 0.86 episodes/day). A median duration of 30 minutes and a median peak intensity score of 7 out of 10 were reported. Time to peak was <10 minutes, 10 to 30 minutes, and 30 minutes in 267 (41.1%), 259 (39.9%), and 30 (4.6%) of the episodes, respectively. Onset of relief occurred after a median of 30 minutes. Time to peak (P < .001) and duration (P = .046) of BTP was shorter in patients with predictable pain (n = 31), who usually were younger than those with unpredictable pain (P = .03). The mean (SD) QoL score was 14.6 (4.6). No difference in QoL between patients with predictable and unpredictable BTP was found (P = .49). Conclusions. In terminally-ill cancer patients, BTP is a severe problem with a negative impact on QoL and has different characteristics according to its predictability.
Background: Opioid refractory pain is a common problem in pain management. Dexmedetomidine is suggested to have opioid-sparing effects, with well-described use in surgical and intensive care unit settings. Some authors advocate its benefit in reducing delirium. Its effects are thought to be exhibited through agonism of pre- and postsynpatic a2-receptors in the central nervous system. It is more selective on a2-receptors than clonidine, accounting for its relatively lower incidence of hypotension. Its use in sedation is favored because it does not depress the respiratory system. The main side effects reported include bradycardia.
Case Description: Twenty-eight-year-old woman with triple negative left breast cancer and a locally destructive tumor was admitted to hospice after exhausting her disease-directed therapy options. Her chief complaint was a throbbing, burning pain to the left chest wall, lower back, and bilateral lower extremities, rated 8/10 on a 10-point verbal scale. Multiple pharmacologic agents for pain, including patient-controlled analgesia infusions with adjuvant methadone and steroids, had failed to provide consistent pain management. Symptoms were difficult to control in the home setting, and she required multiple admissions to our inpatient hospice unit for pain management. She also developed episodes of delirium shortly after hospice admission. We attributed her symptoms to rapid disease progression. After failed pain control with opioids, ketamine, and lidocaine, we trialed a dexmedetomidine infusion. While on the infusion, her pain rating decreased to 0/10 and she had no delirium. Pain recurred soon after cessation of the infusion, initially rated 6/10.
Conclusion: Dexmedetomidine is safe for opioid refractory pain in the hospice inpatient setting. However, its effects may not be sustained. There is potential for use in end-of-life care, with added benefit for possible control of delirium.
BACKGROUND: Methadone may play a role in the control of refractory cancer pain in opioid switching, although some cases fail to switch to methadone.
OBJECTIVE: To evaluate the differences in the clinical aspects in switching to methadone between successful cases (SCs) and unsuccessful cases (UCs).
DESIGN: This was a retrospective study of the clinical aspects of cancer patients who experienced opioid switching from other opioids to methadone.
SETTING/SUBJECTS: Eighty-seven patients who were prescribed oral methadone in our hospital were analyzed. Methadone was initiated from other opioids due to refractory pain in the stop-and-go switching. Among the 87 cases, 7 cases were excluded from further analysis because methadone administration was stopped due to vomiting or self-cessation within six days from switching.
RESULTS: Among the 80 cases who had methadone for seven days or more, 70 cases (SCs) were successful in switching to methadone, according to the Japanese definition, although 10 cases (UCs) who experienced the rapid progression of illness failed due to oral difficulty in the course of titration. In comparison of the clinical characteristics between SCs and UCs, the number of days alive from the start of the administration of methadone was significantly greater in the SCs than in the UCs (SCs: 87.1, UCs: 19, p < 0.0001), but no significant differences were observed for any other factors.
CONCLUSION: From this comparative retrospective study of opioid switching to methadone for cancer pain control between SCs and UCs, early switching to methadone may be useful for patients with advanced cancer pain.
La sédation profonde et continue maintenue jusqu'au décès (SPCMJD) est une intervention médicale qui consiste en l'administration intentionnelle de sédatifs en des dosages et des combinaisons adéquats pour altérer l'état de conscience d'un patient en phase avancée ou terminale, dans le but de soulager ses souffrances réfractaires devenues insupportables. La SPCMJD doit être distinguée de l'anxiolyse, de la sédation modérée, de l'euthanasie, du suicide médicalement assisté, de l'injection létale ou des interventions qui visent directement à hâter la mort du patient. En effet, l'altération de la conscience par sédation, pour faire face aux souffrances réfractaires, implique une sédation proportionnée et la possibilité d'une réversibilité. La SPCMJD est utilisée pour contrôler des symptômes physiques réfractaires comme la dyspnée, la nausée, le vomissement, la douleur physique, mais aussi pour les symptômes psychologiques comme l'anxiété, l'angoisse, le délirium, etc.
Refractory pain is a common manifestation in an oncologic palliative care setting and represents a major challenge for health care professionals involved in care provision. The underlying neoplasm and its dissemination are the foremost pathophysiologic mechanism for the development of pain in patients with advanced cancer. Nonetheless, other etiologies such as trauma and infections need to be considered by clinicians in this particular care setting. The authors present the case of a patient with a recent diagnosis of hepatocellular carcinoma, suffering from intractable neck pain, progressive worsening of her general conditions, and the onset of a generalized seizure. The clinical suspicion of a bacteremia with central nervous system involvement was confirmed by the performed work-up, and a Listeria monocytogenes meningoencephalitis was diagnosed. The purpose of this case report is to raise clinicians' awareness on infectious complications, which may increase the symptom burden in patients treated in an oncologic palliative care setting. Moreover, the manifestation of such complications may be misinterpreted as the consequence of the underlying neoplasm, further delaying the diagnostic and therapeutic management in this particular population.
Opioid therapy must be adjusted to the rhythm of a cancer patient’s pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients. Consecutive adult cancer patients at their EOL treated with long-acting major opioids to control background pain (Numeric Rating Scale = 3/10) were recruited from two Italian palliative care services. Using a personal diary, patients recorded the frequency and onset of BTP episodes and the analgesic rescue therapy taken for each episode over a 7-day period. Rhythms identified in BTP episodes were validated by Cosinor analysis. Overall, 101 patients were enrolled; nine died during the study period. A total of 665 BTP episodes were recorded (average of 7.2 episodes, mean square error 0.8) per patient, with 80.6% of episodes recorded between 8:00 a.m. and 12:00 a.m. At Cosinor analysis, a circadian rhythm of BTP episodes was observed, with a Midline Estimating Statistics of the Rhythm (MESOR) of 1.5, a double amplitude of 1.8, and an acrophase at 12:30 p.m. (p < 0.001). Oral morphine was the most frequent analgesic rescue therapy employed. In terminally-ill cancer patients, BTP episodes follow a circadian rhythm; thus, tailoring the timing of opioid administration to this rhythm may prevent such episodes. This circadian rhythm of BTP episodes in terminally-ill cancer patients should be confirmed in larger samples.
Introduction: Les douleurs réfractaires aux traitements sont un problème en soins palliatifs. Dans ces situations il est possible de réaliser une sédation avec du midazolam. Nous proposons le cas d’une patiente qui a bénéficié d’une sédation-analgésie à la kétamine face à une douleur réfractaire aux traitements usuels.
Présentation du cas: Patiente de 60 ans, poids estimé à 60kg, suivie pour un lymphome B diffus à grandes cellules. La prise en charge est devenue palliative devant l’apparition d’une atteinte méningée avec tétraplégie et d’une altération profonde de son état général. Devant des douleurs réfractaires aux traitements et en accord avec la patiente et sa famille une sédation a été décidée. Une sédation-analgésie de confort a été démarrée avec de la kétamine, une dose de fond de départ à 100mg par jour a été majorée progressivement jusqu'à 150mg en 10jours. Cette sédation-analgésie à la kétamine a permis des moments de réveil plus serein à la patiente lui laissant la possibilité d’échanger avec sa famille à un moment crucial de sa vie.
Discussion: On constate que la sédation-analgésie à la kétamine n’a pas entraîné d’effet indésirable majeur ou inconfortable pour la patiente. Elle a permis de dépasser une situation inextricable en offrant du temps à la patiente et sa famille ce qu’une sédation au midazolam seul n’aurait pas pu faire.
Conclusion: La réalisation d’une sédation-analgésie par kétamine pour la prise en charge de douleurs réfractaires en soins palliatifs semble être une possibilité thérapeutique intéressante à utiliser avant de s’orienter vers une sédation profonde au midazolam seul. Toutefois cette pratique se doit d’être étudiée de façon plus précise par des études cliniques rigoureuses.
One of the major purposes of palliative sedation is to reduce demand for euthanasia. The present paper analyzes a grievous case which demonstrates the killing of a 23-year-old son by his father due to the son's unbearable pain resulting from metastatic colorectal cancer. The article aimed to elaborate the case to figure out whether palliative sedation can be an alternative to euthanasia in a Muslim country. Nevertheless, the analysis of these two end-of-life issues revealed that the limitation of palliative sedation to an expected lifespan of less than 2 weeks as well as the Islamic view on the importance of protecting consciousness preclude reaching a conclusion that palliative sedation can be an alternative to euthanasia in this particular case. Furthermore, in such cases, the primary problem may be the lack of adequate and appropriate palliative care services, rather than the need for euthanasia or palliative sedation.