Palliative sedation

In medicine, specifically in end-of-life care, palliative sedation (also known as terminal sedation, continuous deep sedation, or sedation for intractable distress of a dying patient) is the palliative practice of relieving distress in a terminally ill person in the last hours or days of a dying person's life, usually by means of a continuous intravenous or subcutaneous infusion of a sedative drug, or by means of a specialized catheter designed to provide comfortable and discreet administration of ongoing medications via the rectal route.

As of 2013, approximately tens of millions of people a year were unable to resolve their needs of physical, psychological, or spiritual suffering at their time of death. Considering the amount of intolerable pain the person must face, palliative care if necessary, palliative sedation can provide a more peaceful and ethical solution for such people.[1]

Palliative sedation is an option of last resort for the people whose symptoms cannot be controlled by any other means. It is not a form of euthanasia or physician-assisted suicide, as the goal of palliative sedation is to control symptoms, rather than to shorten or end the person's life.[2]

Palliative sedation is legal everywhere and has been administered since the hospice care movement began in the 1960s.[3] The practice of palliative sedation has been a topic of debate and controversy because many view it as a form of slow euthanasia or mercy killing, associated with many ethical questions. Discussion of this practice occurs in medical literature, but there is no consensus because of unclear definitions and guidelines, with many differences in practice across the world.[4]

Definition

Palliative sedation is the use of sedative medications to relieve refractory symptoms when all other interventions have failed. The phrase 'terminal sedation' was initially used to describe the practice of sedation at end of life, but was changed due to ambiguity in what the word 'terminal' referred to. The term 'palliative sedation' was then used to emphasize palliative care.[5]

The term "refractory symptoms", is defined as symptoms that are impossible to control despite the use extensive therapeutic resources, and that are having an intolerable effect on the patient's well-being in the final stages of life. The symptoms may be physical or psychological or both. The level of consciousness achieved may be mild, intermediate or deep, and the medications may be administered intermittently or continuously.[6]

General practice

Palliative care

Palliative care is aimed to relieve suffering and improve the quality of life for people, as well as their families, with serious and/or life-threatening illness in all stages of disease. It can be provided either as an add-on therapy to the primary curative treatment or as a monotherapy for people who are on end-of-life care.[7] In general, palliative care focuses on managing symptoms, including but not limited to pain, insomnia, mental alterations, fatigue, difficulty breathing, and eating disorders.[8] In order to initiate the care, self-reported information is considered the primary data to assess the symptoms along with other physical examinations and laboratory tests. However, in people at the advanced stage of the disease with potential experience of physical fatigue, mental confusion or delirium which prevent them from fully cooperating with the care team, a comprehensive symptom assessment can be utilized to fully capture all symptoms as well as their severity.[9]

There are multiple interventions that can be used to manage the conditions depending on the frequency and severity of the symptoms, including using medications (i.e. opioid in cancer-related pain), physical therapy/modification (i.e. frequent oral hygiene for xerostomia/dry mouth treatment), or reversal of precipitating causes (i.e. low fiber diet or dehydration in constipation management).[10][11][12]

Palliative sedation

Palliative sedation is often the last resort if the person is resistant to other managing therapies or if the therapies fail to provide sufficient relief for their refractory symptoms, including pain, delirium, dyspnea, and severe psychological distress.[13][14]

In terms of the initiation of palliative sedation, it should be a shared clinical decision initiated preferably between the person receiving treatment and the care team.[15] If severe mental alterations or delirium is the concern for the person to make an informed decision, consent can be obtained in the early stage of the disease or upon the admission to the hospice facility.[16] Family members can only participate in the decision-making process if explicitly requested by the person in care.[17]

Palliative sedation can be used for short periods with the plan to awaken the person after a given time period, making terminal sedation a less correct term. The person is sedated while symptom control is attempted, then the person is awakened to see if symptom control is achieved. In some extreme cases (i.e. for those whose life expectancy is hours or days at the most), palliative sedation is begun with the plan to not attempt to reawaken the person.[18]

Though people may receive palliative care, pharmacologically decreasing a one's consciousness may be the only remaining option to help alleviate intolerable disease symptoms and suffering. Prior to receiving palliative sedation, persons should undergo careful consideration along with their health care team to make sure all other resources and treatment strategies have been exhausted. In the case the person is uncommunicable due to severe suffering, the individual's family member should be consulted as the decreasing the distress of family members is also key component and goal of palliative care and palliative sedation.[4]

The first step in consideration of palliative sedation is assessment of the person seeking the treatment.[19]

There are several states that one may be in that can make palliative sedation the preferred treatment, including but not limited to physical and psychological pain and severe emotional distress. More often than not, refractory or intolerable symptoms give a more sound reason to pursue palliative sedation. Though the interdisciplinary health care team is there to help each person make the most sound medical decision, the individual's judgement is considered to be the most accurate in deciding whether or not their suffering is manageable.[4]

According to a systematic review encompassing over thirty peer-reviewed research studies, 68% of the studies used stated physical symptoms as the primary reason for palliative sedation. The individuals involved in the included studies were terminally ill or suffering from refractory and intolerable symptoms. Medical conditions that had the most compelling reasons for palliative sedation were not only limited to intolerable pain, but include psychological symptoms such as delirium accompanied by uncontrollable psychomotor agitation. Severe trouble breathing (dyspnea) or respiratory distress were also considered a more urgent reason for pursuing palliative sedation. Other symptoms such as fatigue, nausea, and vomiting were also reasons for palliative sedation.[20]

Once assessment is completed and palliative sedation has been decided for the person, a written consent for administration to proceed must be given by the individual. The consent must state their agreement for sedation and lowering their consciousness, regardless each individual's stage in illness or the treatment period of palliative sedation. In order to make a decision, one must be sufficiently informed of their disease state, the specificities and implications of treatment, and potential risks they may face during the treatment. At the time of consent, the person should fully be aware of and understand all necessary legal and medical consequences of palliative sedation. It is also critical that the individual is making the decision upon their own free will, and not under coercion of any sort. The only exception where the individual's consent is not obtained would be in emergency medical situations where one is incapable of making a decision, in which the individual's family or caregiver must give the consent after adequate education, as one would have been given.[4]

Continuous vs. intermittent sedation

Palliative sedation can be administered continuously, until the person's death, or intermittently, with the intention to discontinue the sedation at an agreed upon time. Although not as common, intermittent sedation allows family members of the person's to gradually come to terms with their grief and while still relieving the individual of their distress. During intermittent palliative sedation, the person is still able to communicate with their family members. Intermittent sedation is recommended by some authorities for use prior to continuous infusion to provide the person with some relief from distress while still maintaining interactive function.[21][22][23]

Sedative medications

Sedating agents

Benzodiazepines: This a drug class that works on the central nervous system to tackle a variety of medical conditions, such as seizure, anxiety, depression. As benzodiazepines suppress the activities of nerves in the brain, they also create a sedating effect which is utilized for multiple medical procedures and purposes. Among all benzodiazepine agents, midazolam (Versed) is the most frequently used medication for palliative sedation for its rapid onset and short duration of action. The main indications for midazolam in palliative sedation are to control delirium and alleviate breathing difficulties so as to minimize distress and prevent exacerbation of these symptoms.[24]

Opioids: Opioid agents - which relieve pain primarily via modulation of receptor activity in the central nervous system - also commonly induce sedation or drowsiness. However, they are more frequently used for analgesia than sedation.

Even though opioids tend to provide a comforting effect for recipients, there exists the risk of drug dependence and - to a lesser extent - substance use disorder and diversion of medications. Therefore, the Clinical Practice Guidelines for Quality Palliative Care from the National Consensus Project recommends a comprehensive assessment of symptoms prior to initiating pharmacological therapy; ongoing monitoring to determine efficacy and any adverse effects; and educating the patient and family.[25]

Administration and monitoring

Palliative sedation is administered commonly in hospital or inpatient settings, but also reported to be performed in home care settings.[26] The medication prescribed for palliation will need dose titration to initially manage the refractory symptoms and relieve suffering, and therapy will continue to maintain adequate effect. Prescribed sedatives can be administered intravenously, rectally, etc. on a continuous and/or intermittent basis. When breakthrough symptoms occur, emergency bolus therapy will be needed to maintain symptom management. Both mild and deep levels of sedation may be used to provide relief from suffering, with deeper levels used when death is imminent and a catastrophic event has occurred.[19]

The person being treated will be monitored during palliative sedation to maintain adequate symptom relief, but the following clinical situations will determine a need for dose titration:

  • Person is at end-of-life: Vitals are not monitored except for respiratory rate to assess respiratory distress and tachypnea. The goal is to achieve comfort, so downward titration of sedation is not recommended due to risk of recurrent distress.
  • Person is nearing end-of-life: Vitals such as heart rate, blood pressure, and oxygen saturation, are monitored to maintain physiological stability through sedation. Depending on the risk of a person to have respiratory depression or become unstable, the treatment dose may need to be adjusted or a benzodiazepine antagonist may be administered.
  • Suffering managed and symptom controlled: Sedation may be carefully lowered for lucidity. This would provide possibility of reevaluating the person's preferences for care or allow family communication.[19]

Nutrition and fluids

As people undergoing terminal sedation are typically in the last hours or days of their lives, they are not usually eating or drinking significant amounts. There have not been any conclusive studies to demonstrate benefit to initiating artificial nutrition (TPN, tube feedings, etc.) or artificial hydration (subcutaneous or intravenous fluids). There is also a risk that IV fluids or feedings can worsen symptoms, especially respiratory secretions and pulmonary congestion. If the goal of palliative sedation is comfort, IV fluids and feedings are often not consistent with this goal.[27]

A specialized rectal catheter can provide an immediate way to administer small volumes of liquids for people in the home setting when the oral route is compromised. Unlike intravenous lines, which usually need to be placed in a hospital environment,[28] the rectal catheter can be placed by a clinician, such as a hospice nurse or home health nurse, in the home. This is useful for people who cannot swallow, including those near the end of life (an estimated 1.65 million people are in hospice care in the US each year[29]).

Before initiating terminal sedation, a discussion about the risks, benefits and goals of nutrition and fluids is encouraged, and is mandatory in the United Kingdom.[30]

Sedation vs. euthanasia

Titrated sedation might speed death but death is considered a side effect and sedation does not equate with euthanasia.[27][31]

The primary difference between palliative sedation, relief of severe pain and symptoms, and euthanasia, the intentional ending of a person's life, is both their intent and their outcome. At the end of life sedation is only used if the individuals perceives their distress to be unbearable, and there are no other means of relieving that distress. The intended goal is to provide them some relief of their suffering through the use benzodiazepines and other agents which inadvertently may increase the risk of death. Studies have been conducted however, showing that the risk of death through palliative sedation is much lower than earlier perceived. This has raised the argument that palliative sedation does not cause or hasten death and that an individuals death following palliative sedation is more likely to be due to their disease - the measure of success of palliative sedation remains relief of a person's symptoms until their end of life. On the other hand, euthanasia is performed with the intent to permanently relieve the person of their pain through death - the measure of success being their death.[22]

In palliative care the doses of sedatives are titrated (i.e., varied) to keep the individual comfortable without compromising respiration or hastening death. Death results from the underlying medical condition. For more information on the palliative care use of sedatives and the safe use of opioids see opioids.[32][33]

People (or their legal representatives) only have the right to refuse treatments in living wills; however, the demand of life saving treatments, or any treatments at all is controversial among states and heavily depends on each specific situation.[34] However, once unconsciousness begins, as the person is no longer able to decide to stop the sedation or to request food or water, the clinical team can make decisions for the individual. A Living Will, made when competent, can, under UK law, give a directive that the person refuses 'Palliative Care' or 'Terminal Sedation', or 'any drug likely to suppress my respiration'.[35]

The use of sedation for palliative care in the UK was considered as part of an independent review of the Liverpool Care Pathway for the Dying Patient. Families of patients in some instances said that they thought the doses of sedatives prevented patients from asking for water leading to death from dehydration,[36]: 1.66  there were many accounts of subcutaneous infusions being started as a matter of course rather than to control a specific symptom, there were many reports of patients being left alone for a short-period of time by their families only to find that sedation had been administered leaving them unable to speak to their relatives;[36]: 1.69  relatives and carers reported instances where they felt that the administration of morphine had directly lead to the death of a patient.[36]: 1.68 

Physician-assisted Suicide

As of 2020, Assisted suicide in the United States, otherwise known as medical aid in dying, is legal in ten jurisdictions (California, Colorado, District of Columbia, Hawaii, Maine, Montana, New Jersey, Oregon, Vermont, and Washington).[37][38]

Epidemiology

Prevalence

In a review of research articles on various aspects of palliative care, the prevalence of palliative sedation was reported as highly varied. In palliative care units or hospice, the prevalence ranged from 3.1%-51%.[39][40] In the home care setting, two Italian studies reported a prevalence of 25% and 52.5%.[41][42] Hospital-based palliative support teams vary in prevalence, with reports of 1.33% and also 26%.[39][43] Different countries also report large differences in prevalence of palliative sedation:[44][45][46]

Country Prevalence
Netherlands 10%
Belgium 8.2%
Italy 8.5%
Denmark 2.5%
Switzerland 4.8%
Sweden 3%

A 2009 survey of almost 4000 U.K. people whose care had followed the Liverpool Care Pathway for the Dying Patient found that while 31% had received low doses of medication to control distress from agitation or restlessness, only 4% had required higher doses.[47]

Almost half of the studies reviewed differentiated intermittent versus continuous palliative sedation. The prevalence of intermittent sedation was 30% -67% of cases and continuous sedation was 14-68% of cases. People starting intermittent sedation may progress to use of continuous sedation in 10 - 27% of cases. The prevalence of mild versus deep sedation was also reported: one study reported 51% of cases used mild sedation and 49% deep sedation;[48] a second study reported 80% of cases used mild sedation and 20% deep sedation.[49]

Survival

There are reports that after initiation of palliative sedation, 38% of people died within 24 hours and 96% of people died within one week. Other studies report a survival time of < 3 weeks in 94% of people after starting palliative sedation. Some physicians estimate that this practice shortens life by ≤24 hours for 40% of people and > 1 week for 27% of people. Another study reported people receiving sedation in their last week of life survived longer than those who did not receive sedation, or only received sedation during last 48 hours of life.[20]

According to 2009 research, 16.5% of all deaths in the United Kingdom during 2007–2008 took place after continuous deep sedation.[50][51][52]

History of hospice

U.S. hospice care movement

Hospice care emphasizes palliative, rather than curative, treatment to support individuals during end-of-life care when all other alternatives have been exhausted. It differs vastly from other forms of healthcare because both the person and the family are included in all decision-making and aims to treat the individual, not the disease.[53] The Hospice Care Movement began in the United States during the 1960s and was influenced heavily on the model published by St. Christopher's Hospice of London located in Great Britain. Despite differing setting, services, and staffing, the U.S. hospice care movement still sought to maintain the goals and philosophy of St. Christopher's model which centered on symptom control to allow the person to die with freedom, rather than attempting curative treatment.[54]

The first Hospice in the United States, Connecticut Hospice, was founded by Florence Wald and opened in 1974.[55] Supporters of the movement faced many challenges early on, the biggest being the lack of insurance coverage for hospice care services. Initiatives to increase public awareness of the movement were created to combat this obstacle and supply the movement with public funding in order to maintain their services. One of the greatest accomplishments made by the movement was in the inclusion of hospice care in services covered under Medicare in 1982. This victor prompted the creation of National Hospice Week by President Reagan to take place from November 7–14 as a form of recognition to the vital impact nurses and caregivers have on these individuals and their families.[56][57] Less than five decades after the first hospice program began, there are now over 4,000 programs in place under the umbrella of a multi-billion dollar industry. The cumulative budget for hospice programs nationwide increased from 10 million in the late 1970s, to 2.8 billion dollars in 1995, and 10 billion in 2008.[56]

Policies

United States

In 2008, the American Medical Association Council on Ethical and Judicial Affairs approved an ethical policy regarding the practice of palliative sedation.[58][59] There is no specific law in barring the practice of palliative sedation, and the U.S. Conference of Catholic Bishops is reported to accept the practice of keeping people pain free at end of life.[60]

Sweden

In October 2010 Svenska Läkaresällskapets, an association of physicians in Sweden, published guidelines which allowed for palliative sedation to be administered even with the intent of the terminally ill person not to reawaken.[61]

See also

Notes

  1. ↑ Lipman, Arthur G. (2013-10-11). "The Iahpc Manual of Palliative Care, 3Rd Edition". Journal of Pain & Palliative Care Pharmacotherapy. 27 (4): 408–409. doi:10.3109/15360288.2013.848970. ISSN 1536-0288. S2CID 70444188.
  2. ↑ Ollove M (2018). "Assisted suicide is controversial, but palliative sedation is legal and offers peace". The Washington Post. Retrieved 31 July 2020.
  3. ↑ Ollove M (2 July 2018). "Palliative Sedation, an End-of-Life Practice That Is Legal Everywhere". pew.org. Retrieved 2020-05-12.
  4. 1 2 3 4 Collège des médecins du Québec. (2016). Palliative sedation at the end of life. Collège des médecins du Québec. ISBN 978-2-924674-01-7. OCLC 1032943909.
  5. ↑ Twycross R (2019-01-01). "Reflections on palliative sedation". Palliative Care. 12: 1178224218823511. doi:10.1177/1178224218823511. PMC 6350160. PMID 30728718.
  6. ↑ [l.https://epe.lac-bac.gc.ca/100/200/300/cmq/palliative_sedation/LaSedationPalliativeEnFinDeVie_EN_final.pdf "Guidelines"] (PDF). Palliative At the End of Life. Retrieved August 8, 2020.
  7. ↑ Sepúlveda C, Marlin A, Yoshida T, Ullrich A (August 2002). "Palliative Care: the World Health Organization's global perspective". Journal of Pain and Symptom Management. 24 (2): 91–6. doi:10.1016/s0885-3924(02)00440-2. PMID 12231124.
  8. ↑ Moens K, Higginson IJ, Harding R (October 2014). "Are there differences in the prevalence of palliative care-related problems in people living with advanced cancer and eight non-cancer conditions? A systematic review". Journal of Pain and Symptom Management. 48 (4): 660–77. doi:10.1016/j.jpainsymman.2013.11.009. PMID 24801658.
  9. ↑ Williams PD, Graham KM, Storlie DL, Pedace TM, Haeflinger KV, Williams DD, et al. (2013). "Therapy-related symptom checklist use during treatments at a cancer center". Cancer Nursing. 36 (3): 245–54. doi:10.1097/NCC.0b013e3182595406. PMID 22744208. S2CID 25542219.
  10. ↑ Quigley C (July 2008). "Opioids in people with cancer-related pain". BMJ Clinical Evidence. 2008. PMC 2907984. PMID 19445735.
  11. ↑ Sweeney MP, Bagg J (2000). "The mouth and palliative care". The American Journal of Hospice & Palliative Care. 17 (2): 118–24. doi:10.1177/104990910001700212. PMID 11406956. S2CID 11335237.
  12. ↑ Erichsén E, Milberg A, Jaarsma T, Friedrichsen MJ (July 2015). "Constipation in Specialized Palliative Care: Prevalence, Definition, and Patient-Perceived Symptom Distress". Journal of Palliative Medicine. 18 (7): 585–92. doi:10.1089/jpm.2014.0414. PMID 25874474.
  13. ↑ Cherny NI, Portenoy RK (1994). "Sedation in the management of refractory symptoms: guidelines for evaluation and treatment". Journal of Palliative Care. 10 (2): 31–8. doi:10.1177/082585979401000207. PMID 8089815. S2CID 37963182.
  14. ↑ Garetto F, Cancelli F, Rossi R, Maltoni M (October 2018). "Palliative Sedation for the Terminally Ill Patient". CNS Drugs. 32 (10): 951–961. doi:10.1007/s40263-018-0576-7. PMID 30259395. S2CID 52842088.
  15. ↑ Miccinesi G, Caraceni A, Maltoni M (December 2017). "Palliative sedation: ethical aspects". Minerva Anestesiologica. 83 (12): 1317–1323. doi:10.23736/S0375-9393.17.12091-2. PMID 28707846.
  16. ↑ Maltoni M, Pittureri C, Scarpi E, Piccinini L, Martini F, Turci P, et al. (July 2009). "Palliative sedation therapy does not hasten death: results from a prospective multicenter study". Annals of Oncology. 20 (7): 1163–9. doi:10.1093/annonc/mdp048. PMID 19542532.
  17. ↑ Laryionava K, Pfeil TA, Dietrich M, Reiter-Theil S, Hiddemann W, Winkler EC (February 2018). "The second patient? Family members of cancer patients and their role in end-of-life decision making". BMC Palliative Care. 17 (1): 29. doi:10.1186/s12904-018-0288-2. PMC 5816525. PMID 29454337.
  18. ↑ Cherny NI, Radbruch L (October 2009). "European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care". Palliative Medicine. 23 (7): 581–93. doi:10.1177/0269216309107024. PMID 19858355. S2CID 16972842.
  19. 1 2 3 Cherny N. "Palliative sedation". UpToDate. Retrieved 2020-05-12.
  20. 1 2 Claessens P, Menten J, Schotsmans P, Broeckaert B (September 2008). "Palliative sedation: a review of the research literature". Journal of Pain and Symptom Management. 36 (3): 310–33. doi:10.1016/j.jpainsymman.2007.10.004. PMID 18657380.
  21. ↑ "Scottish Palliative Care Guidelines - Severe Uncontrolled Distress". Scottish Palliative Care Guidelines. Retrieved 2020-07-31.
  22. 1 2 Olsen ML, Swetz KM, Mueller PS (October 2010). "Ethical decision making with end-of-life care: palliative sedation and withholding or withdrawing life-sustaining treatments". Mayo Clinic Proceedings. 85 (10): 949–54. doi:10.4065/mcp.2010.0201. PMC 2947968. PMID 20805544.
  23. ↑ Morita T, Inoue S, Chihara S (July 1996). "Sedation for symptom control in Japan: the importance of intermittent use and communication with family members". Journal of Pain and Symptom Management. 12 (1): 32–8. doi:10.1016/0885-3924(96)00046-2. PMID 8718914.
  24. ↑ Mercadante S, Porzio G, Valle A, Aielli F, Casuccio A (May 2014). "Palliative sedation in patients with advanced cancer followed at home: a prospective study". Journal of Pain and Symptom Management. 47 (5): 860–6. doi:10.1016/j.jpainsymman.2013.06.019. hdl:10447/96890. PMID 24099896.
  25. ↑ "National Consensus Project for Quality Palliative Care (NCP) | NCHPC | National Coalition For Hospice and Palliative Care". Retrieved 2020-07-31.
  26. ↑ Mercadante S, Porzio G, Valle A, Fusco F, Aielli F, Adile C, Casuccio A (June 2012). "Palliative sedation in advanced cancer patients followed at home: a retrospective analysis". Journal of Pain and Symptom Management. 43 (6): 1126–30. doi:10.1016/j.jpainsymman.2011.06.027. hdl:10447/78143. PMID 22651952.
  27. 1 2 Maltoni M, Pittureri C, Scarpi E, Piccinini L, Martini F, Turci P, et al. (July 2009). "Palliative sedation therapy does not hasten death: results from a prospective multicenter study". Annals of Oncology. 20 (7): 1163–9. doi:10.1093/annonc/mdp048. PMID 19542532.
  28. ↑ Plumer AL. 2007. Plumer's Principles and Practices of Intravenous Therapy. Lippincott Williams & Wilkins.
  29. ↑ "National Hospice and Palliative Care Organization's Facts and Figures: Hospice Care in America, 2013 Edition" Archived 2017-06-17 at the Wayback Machine, nhpco.org; accessed January 5, 2018.
  30. ↑ Twycross R (2019-01-27). "Reflections on palliative sedation". Palliative Care. 12: 1178224218823511. doi:10.1177/1178224218823511. PMC 6350160. PMID 30728718.
  31. ↑ Beller EM, van Driel ML, McGregor L, Truong S, Mitchell G (January 2015). "Palliative pharmacological sedation for terminally ill adults" (PDF). The Cochrane Database of Systematic Reviews. 1: CD010206. doi:10.1002/14651858.CD010206.pub2. PMC 6464857. PMID 25879099.
  32. ↑ Maltoni M, Scarpi E, Rosati M, Derni S, Fabbri L, Martini F, et al. (April 2012). "Palliative sedation in end-of-life care and survival: a systematic review". Journal of Clinical Oncology. 30 (12): 1378–83. doi:10.1200/JCO.2011.37.3795. PMID 22412129.
  33. ↑ Teoh PJ, Camm CF (2012). "NICE Opioids in Palliative Care (Clinical Guideline 140) - A Guideline Summary". Annals of Medicine and Surgery. 1: 44–8. doi:10.1016/S2049-0801(12)70013-4. PMC 4523168. PMID 26257908.
  34. ↑ Winick BJ (1997). "The future of the right to refuse treatment.". The right to refuse mental health treatment. Washington: American Psychological Association. pp. 391–402. doi:10.1037/10264-020. ISBN 1-55798-369-0.
  35. ↑ "Advance decision (living will)". nhs.uk. 2018-05-29. Retrieved 2020-07-27.
  36. 1 2 3 A review of the liverpool care pathway. Department of Health Ministers.
  37. ↑ "Assisted Suicide Laws in the United States". Patients Rights Council. February 6, 2012. Retrieved August 4, 2020.
  38. ↑ Research, CNN Editorial (26 November 2014). "Physician-Assisted Suicide Fast Facts". CNN. Retrieved 2020-07-31.
  39. 1 2 "Comprehensive Management of Cancer Pain Including Surgery". Springer Reference. SpringerReference. Berlin/Heidelberg: Springer-Verlag. 2011. doi:10.1007/springerreference_143670.
  40. ↑ Kohara H, Ueoka H, Takeyama H, Murakami T, Morita T (February 2005). "Sedation for terminally ill patients with cancer with uncontrollable physical distress". Journal of Palliative Medicine. 8 (1): 20–5. doi:10.1089/jpm.2005.8.20. PMID 15662170.
  41. ↑ Ventafridda V, Ripamonti C, De Conno F, Tamburini M, Cassileth BR (1990). "Symptom prevalence and control during cancer patients' last days of life". Journal of Palliative Care. 6 (3): 7–11. doi:10.1177/082585979000600303. PMID 1700099. S2CID 25084289.
  42. ↑ Peruselli C, Di Giulio P, Toscani F, Gallucci M, Brunelli C, Costantini M, et al. (May 1999). "Home palliative care for terminal cancer patients: a survey on the final week of life". Palliative Medicine. 13 (3): 233–41. doi:10.1191/026921699669863369. PMID 10474710. S2CID 22537419.
  43. ↑ Stone P, Phillips C, Spruyt O, Waight C (March 1997). "A comparison of the use of sedatives in a hospital support team and in a hospice". Palliative Medicine. 11 (2): 140–4. doi:10.1177/026921639701100208. PMID 9156110. S2CID 31506323.
  44. ↑ Miccinesi G, Rietjens JA, Deliens L, Paci E, Bosshard G, Nilstun T, et al. (February 2006). "Continuous deep sedation: physicians' experiences in six European countries". Journal of Pain and Symptom Management. 31 (2): 122–9. doi:10.1016/j.jpainsymman.2005.07.004. PMID 16488345.
  45. ↑ Rietjens JA, van der Heide A, Vrakking AM, Onwuteaka-Philipsen BD, van der Maas PJ, van der Wal G (August 2004). "Physician reports of terminal sedation without hydration or nutrition for patients nearing death in the Netherlands". Annals of Internal Medicine. 141 (3): 178–85. doi:10.7326/0003-4819-141-3-200408030-00006. hdl:1765/10355. PMID 15289214. S2CID 2244009.
  46. ↑ van der Heide A, Onwuteaka-Philipsen BD, Rurup ML, Buiting HM, van Delden JJ, Hanssen-de Wolf JE, et al. (May 2007). "End-of-life practices in the Netherlands under the Euthanasia Act". The New England Journal of Medicine. 356 (19): 1957–65. doi:10.1056/NEJMsa071143. PMID 17494928.
  47. ↑ End of Life Care Audit: Dying in Hospital (14 September 2009). "National Care of the Dying Audit 2009". Royal College of Physicians.
  48. ↑ Morita T, Tsunoda J, Inoue S, Chihara S (May 1999). "The decision-making process in sedation for symptom control in Japan". Palliative Medicine. 13 (3): 262–4. doi:10.1177/026921639901300313. PMID 10474717. S2CID 1298076.
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