Reporting of Palliative Sedation and Use of Opioids at the End of Life in a Belgian University Hospital: A Pilot Study

Abstract

Background:

Palliative sedation requires no formal registration in Belgium. For euthanasia, however, there are clear guidelines in certain countries, including mandatory registration and evaluation of cases. Official guidelines have been developed for palliative sedation, but research still shows unskilled use of sedation and unclear demarcation between palliative sedation and euthanasia. Registration could be used to avoid unskilled use of sedation and to avoid use or abuse of sedation to hasten the patient's death (described as “slow/passive euthanasia”).

Objective:

To evaluate the current practice of palliative sedation and use of opioids and sedatives at the end of life by using a registration document.

Design:

Retrospective observational study.

Setting/Subjects:

We included all in-hospital deaths at an academic hospital in Belgium of patients (age ≥18 years) who had received parenteral opioids, benzodiazepines, barbiturates, or other anesthetics during the last 24 hours.

Measurements:

We investigated indications for palliative sedation, patients' and physicians' characteristics, types of medication used, and the decision-making process with the patients and family. The questionnaires were collected between July 9 and November 25, 2016. The study was approved by the Biomedical Ethics Committee of UZ Brussel (B.U.N. 1432016293).

Results:

In a population of 124 patients, refractory symptoms were reported in 94.4%. All patients received parenteral opioids (intravenously). Benzodiazepines were used in 51.6%. In 75.8%, physicians reported no change in treatment plan during end of life. Hastening death by increasing analgesics and/or sedatives was mentioned in 19.3%. The treatment plan was discussed with patients in 26.6% of cases. In 6 cases, an explicit intention to hasten death was mentioned; in 36 cases, doses of opioids/sedatives may not have been strictly proportional to symptoms.

Conclusion:

This Belgian study shows that objective reporting of palliative sedation can be used as a tool to ensure good clinical practice where patients receive the most appropriate end-of-life care, avoiding abusive and injudicious or unskilled use of sedation.

Introduction

In the Dutch-speaking part of Belgium (Flanders) ∼70% of all deaths occur in patients who are expected to die.¹ In up to 50% of all these nonsudden deaths, a decision is made that possibly or certainly hastens death.² These end-of-life decisions include withdrawing or withholding life-prolonging treatment, intensified alleviation of symptoms with a possible life-shortening effect, euthanasia, physician-assisted suicide, the use of lethal drugs without the patient's explicit request, and palliative sedation.^1–3

Sedation can be mild or deep, intermittent or continuous, and is used to lower the level of consciousness in unbearable and refractory symptoms without the intent to hasten death.⁴

In 2001, a large-scale study in six different European countries showed a prevalence of continuous deep sedation of 2.5%, up to 8.5% of all deaths (in hospitals and/or other care settings).⁵

The overall prevalence of continuous deep sedation until death in Flanders, Belgium increased from 8.2% of all deaths in 2001 to 14.5% in 2007 and stabilized at 12% in 2013.^1,6

With an aging population and an increasing incidence of cancer and of nonmalignant incurable diseases, more and more physicians will be confronted with palliative care and end-of-life decisions.^7–10

For euthanasia, legalized in Belgium since 2002, there are clear guidelines, including mandatory registration and evaluation of cases.¹¹ Although several guidelines have also been developed for palliative sedation, research still shows unskilled use of sedation and a lack of clear demarcation between palliative sedation and euthanasia.^4,12–15 Sometimes, sedation is used (or abused) to hasten the patient's death (described as “slow/passive euthanasia”).^16–18

However, palliative sedation in Belgium requires no formal reporting, in contrast to countries such as Canada, where registration of this practice is required by law and a written informed consent from the patient or representative must be obtained by the physician before initiating any form of palliative sedation, irrespective of its expected depth or duration.^14,17,19,20 Detailed reporting of concrete palliative sedation cases may possibly also be necessary in Belgium, to thoroughly evaluate the current practice of palliative sedation and subsequently plan actions for improvements wherever appropriate.^16,21

In this pilot study, reporting was done retrospectively within two weeks after the death of the patient. Reporting included items on meeting the conditions for palliative sedation, the procedure followed by the doctor, and how palliative sedation was administered.

However, it is important that the therapeutic choices made by the patient(s) in consultation with the physician are adhered to as strictly as possible, in the interests of the patient and their family, in accordance with the ethical standards assumed in this respect.²² It is therefore of the utmost importance that concrete research is carried out into how this decision can be better guided and made more transparent at the end of life.⁷

The aim of the investigation was to evaluate the current practice of palliative sedation and the use of opioids and sedatives at the end of life by using a registration document.

Materials and Methods

In this study, we registered all palliative sedation cases in a university hospital in Belgium, calculated the prevalence, and investigated the indications for palliative sedation in these cases, the patients' and physicians' characteristics, the types of medication used, and the decision-making process with patients and family members preceding sedation.

Design and patient recruitment

This retrospective observational study was performed in an academic hospital in Belgium. All in-hospital deaths of patients, being 18 years or older, having received parenteral opioids, benzodiazepines, barbiturates, or other anesthetics during the last 24 hours of life were registered and included in the study. Patients treated merely with oral pain medication or benzodiazepines, euthanasia patients (legalized in Belgium), or sudden death patients (WHO definition: nonviolent, unexpected death occurring less than 24 hours from the onset of symptoms) were excluded from registration.²³

A questionnaire, elaborated by the palliative support team and based on previous (unpublished) observations, was filled out by the physician who attended the patient during the end-of-life period. Doctors in training were all supervised by a senior doctor. Patients' treatments were discussed daily with senior doctors. When several physicians were involved, the questionnaire was filled out by the physician who attended the patient daily or most frequently.

A physician in his last year of training, specializing in geriatric medicine (N.M.), collected all the questionnaires and ensured procedure compliance, which was also supported by the fact that hospital management made the registration of these cases and completion of the questionnaire mandatory.

The questionnaires were collected between July 9 and November 25, 2016. Anonymous patient data, clinical characteristics of patients (diseases, symptoms, general treatment regime), and end-of-life treatments (indication for the decision: when to start treatment with opioids or sedatives), drugs used, administration of artificial nutrition and/or hydration, and availability of informed consent were recorded. Characteristics of the physician (age, qualification, perception) were collected.

The attending physician gave written informed consent. Personal patient data were not registered in the questionnaire. The study was approved by the Biomedical Ethics Committee of UZ Brussel (O.G. 016), B.U.N. 143201629398.

The focus of this pilot study was to present a detailed description of therapeutic practices of physicians in hospitalized patients where death is the expected short-term outcome, by using a registration document. The decisions at the end of life, indications for using opioids and sedation, types of medication used, and physician's intentions were documented. It was investigated whether adequate information was given and/or an informed consent was obtained from patients and/or their family. To the best of our knowledge, this has not been done retrospectively in Europe until now. The study proved feasible and compliance high; reasons for this were the support from management (the hospital CEO had sent a letter with a call for cooperation), approval from the medical board, and presenting the study as a learning opportunity.

Statistics

Statistical analysis was performed using IBM SPSS version 23.0. Descriptive statistics were computed for all included variables (frequency distributions, measures of central tendency, etc.).

Results

Characteristics of patients/deaths

This pilot study was conducted between July and November 2016. A total of 291 patients died in the academic hospital between July 9, and November 25, 2016. In this group, 167 patients were excluded from the study: 123 patients died suddenly (73.7%), 8 patients were younger than 18 (4.8%), 20 patients underwent euthanasia (12.0%), and 16 patients were expected to die but did not receive any subcutaneous (SC) or intravenous (IV) opioids, benzodiazepines, barbiturates, or other anesthetics (9.6%).

A total of 124 deaths were registered and included in this study: 81.5% of the diseased persons were 65 years of age or older, and 58.1% were male (Table 1). Causes of death were: oncological (37.1%), cardiovascular (8.1%), respiratory (13.7%), stroke (12.1%), neurological diseases (16.1%), or other (12.9%) (e.g., sepsis).

Table 1.

Patient Characteristics

	No. of cases (n = 124)	Percentages (%)
Age in years (mean 75.9, range 28–102)
18–49	7	5.6
50–64	16	12.9
65–79	42	33.9
>79	59	47.6
Sex
Female	52	41.9
Male	72	58.1
Underlying disease
Oncological	46	37.1
Cardiovascular	10	8.1
Respiratory	20	13.7
Stroke	15	12.1
Neurological diseases	20	16.1
Other	16	12.9
Refractory symptoms^a	117	94.4
Pain	69	59.0
Dyspnea	74	63.2
Delirium	36	30.8
Nausea or vomiting	15	12.8
Fatigue	28	24.1
Agitation	61	52.1
Anxiety	17	14.5
Depression	5	4.3
Existential distress	5	4.3
Other	9	7.7
Place of death
Intensive care unit	15	12.1
Department of Internal Medicine	86	69.4
Department of Surgery	9	7.3
Department of Neurology	14	11.3
Emergency unit	0	0.0

Multiple symptoms are possible.

In 117 cases, refractory symptoms were reported (sometimes multiple ones) by the treating physician. These symptoms included pain (59.0%), dyspnea (63.2%), delirium (30.8%), nausea or vomiting (12.8%), fatigue (24.1%), agitation (52.1%), anxiety (14.5%), depression (4.3%), and existential distress (4.3%). Other symptoms (7.8%) were convulsions, fever, bladder spasms, and tachycardia.

Fifteen patients died in intensive care (12.1%), 86 patients in the Department of Internal Medicine (69.4%), 9 patients in the Department of Surgery (7.3%), and 14 patients in the Department of Neurology (11.3%). There were no nonsudden deaths reported in the emergency unit.

Characteristics physicians

Fifty physicians participated and gave informed consent. Most of the physicians were under 35 years of age (77.4%) and still in training (74.2%), mainly in internal medicine (70.2%) (Table 2).

Table 2.

Characteristics of Treating Physicians

	Percentages (%)
Age of physician in years
≤34	77.4
35–44	16.9
45–54	4.8
≥55	0.8
Sex
Female	55.6
Male	44.4
Training status
Physician in training	74.2
Graduated physician	25.8
Specialism
Internal medicine	70.2
Other	29.8

End-of-life decisions

In 95.2% of patients, death was expected within two weeks (Table 3). To treat refractory symptoms, a decision to increase administration of parenteral opioids was made in 55.6% of the patients, palliative sedation was started in 15.3%, and a combination of sedation and dose increase of parenteral opioids was reported in 29% of cases. There was no intention to hasten death in 67.7% (at the time of starting opioids or sedatives). In 27.4%, the physicians judged that the chosen treatment might have a life-shortening effect and indicated disproportional use of opioids/sedatives. In four cases (3.2%), palliative sedation was indicated on the registration document, whereas only opioids were administered, without sedatives (not in Table 3). Explicit intention to hasten death was reported in six cases (4.8%). When making the initial decision (when to start administering opioids or sedatives), artificial hydration was stopped in 54.9% of cases and nutrition in 77.4%.

Table 3.

End-of-Life Decisions Taken by Physicians

	No. of cases (n = 124)	Percentages (%)
Expected decease by physician (less than or equal to two weeks)	118	95.2
Initial decision
Treatment strategy
Adjusting or increasing of parenteral analgesia/opioids	69	55.6
Palliative sedation	19	15.3
Combination of sedation and adjusting or increasing parenteral analgesia/opioids	36	29.0
Nutrition and hydration
Stop artificial hydration	68	54.9
Stop nutrition	96	77.4
Intention of hastening death
No intention	84	67.7
Not strictly proportional dosing of opioids/sedatives	34	27.4
Explicit intention	6	4.8
Change to therapy goals at end-of-life phase admission
No change	94	75.8
Change (more than one change possible)
Intention of hastening death by increasing dose of analgesia and/or sedatives	27	19.3
Stop artificial hydration	5	4.0
Stop nutrition	4	3.1
Reason for change in therapy goals (n = 30)
Suffering took too long in the family's view	10	33.3
Suffering took too long in the treating physician's view	20	66.7
Suffering took too long in the nursing staff's view	9	30
Explicit request of the patient	5	16.7

To alleviate refractory symptoms, opioids were administrated IV in 83.1%, SC in 37.9%, and transcutaneously in 11.3% of the patients, at any given moment (Table 4). During the last 24 hours of life, all patients received parenteral opioids (IV). Benzodiazepines (midazolam/diazepam) were used in 51.6% of the patients (IV 49.2%; SC 4.0%). Barbiturates (phenobarbital) and anesthetics (propofol) were only administered IV and were reported in 6% and 7% of cases, respectively.

Table 4.

Type of Medication Used+Time Until Death after Initial Decision

	No. of cases (n = 124)	Percentages (%)
Drugs administered
Opioids	124	100
Intravenously	103	83.1
Subcutaneously	47	37.9
Transcutaneously	14	11.3
Benzodiazepines (midazolam/diazepam)	64	51.6
Intravenously	61	49.2
Subcutaneously	5	4.0
Barbiturates (phenobarbital) (IV)	6	4.8
Anesthetics (propofol) (IV)	7	5.6
Time until death after initial administration
<4 hours	20	16.1
<12 hours	15	12.1
<24 hours	29	23.4
One to three days	46	37.1
Less than one week	9	7.3
More than one week	4	3.2
No information	1	0.8

IV, intravenously.

The decision-making process

In the majority of the patients (75.8%), physicians reported no change in therapy goals at the end of life. When patient care goals did change, however, hastening death by increasing doses of analgesics and/or sedatives was mentioned in 19.3%, artificial hydration was stopped in 4.0%, and nutrition in 3.1%. Physicians were asked for reasons leading to a change in therapy goals. The following reasons were mentioned (as indicated by the reporting physician): (1) Suffering took too long in the view of the family (33.3%)/the physician (66.7%)/the nursing staff (30%), (2) explicit request of the patient (16.7%).

Approximately 50% of patients died within 24 hours after starting opioids and/or sedatives. Patients had been informed about life expectancy (52.4%), therapeutic options (48.4%), and palliative care (42.7%). During the last days of their life, the treatment plan (care goals for the patient) was discussed with the patient in merely 26.6% of the cases. Unconsciousness/incompetency was the main reason for “no consultation” (97.8%). Family and paramedics were consulted to determine patient care goals and a new treatment plan for the patient in 96% and 93.5% of cases, respectively. In 8.9%, the patient requested euthanasia but died before the procedure was legally completed (Table 5).

Table 5.

Consent/Consultation Patient/Family and (Para)Medics

	No. of cases (n = 124)	Percentages (%)
Patient was informed about
Life expectancy	65	52.4
Therapeutic options	60	48.4
Palliative care	53	42.7
Consultation with patient in the last stage of life	33	26.6
No consultation with patient	91	73.4
Decreased level of consciousness	89	97.8
Legally incompetent	1	1.1
Overt discussion deemed to have negative effect on the patient	1	1.1
Family informed in the last stage of life	119	96
Consultation with (para)medics in the last stage of life	116	93.5
Nursing staff	82	66.1
Other physician	106	85.5
Physician palliative support team	17	13.7
Social nurse	13	10.5
Psychologist	14	11.3
Patient's request for euthanasia	11	8.9

Discussion

This study reveals that a little more than half of all deaths (55.0%) occurred nonsuddenly but were predicted. In 37.5% (n = 60) of these nonsudden deaths, treating physicians reported that decisions were made that possibly or certainly hastened death (euthanasia included, n = 20). These results are lower than the results from two previous studies that showed 47.8% and 50% of decisions possibly or certainly hastened death.^1,2 However, these earlier studies focused on a general population, rather than only including hospitalized patients receiving tertiary health care. In 94.4% of patients included in the study, refractory symptoms were reported. The most common refractory symptoms were: pain (59.0%), dyspnea (63.2%), delirium (30.8%), and agitation (52.1%).

The decision to sedate patients with the intention to treat refractory symptoms was made in 55 cases (19.4% of all deaths (n = 283); children were not included). These figures correspond with previously reported data: in Belgium the prevalence of “continuous deep sedation” in hospital settings was estimated at 19.5% (2007) and 17% (2013).⁶ Approximately 50% of patients died within 24 hours after starting treatment of refractory symptoms with opioids and/or sedatives (irrespective of whether this was labeled as “continuous deep sedation”). Artificial hydration was stopped in 54.9% and nutrition in 77.4%. Decisions about hydration and/or artificial nutrition are widely discussed in literature and should be made independently from sedation.^24–26

In a terminal condition and where there is unbearable suffering, all meaningless life support treatments may be discontinued. This action is considered to be good clinical practice in Belgium.²⁷ Artificial nutrition can only be considered in an acute, reversible condition.²⁷

Physicians reported that they only consulted patients about medical decisions (that could hasten death) during the last stages of life in 26.6% of cases. These findings are similar to previously published data by Robijn et al., where requests or consensus obtained from hospitalized patients to perform palliative sedation were only registered in 30% to 35% of cases (30% in 2007 and 35% in 2013).⁶ These results suggest that, during the last days of their life, patient consent to the treatment plan is often lacking. In our study, unconsciousness/incompetency was the main reason for “no consultation” (97.8%). However, it is important that in end-of-life decisions, the patient's family (96%) and medics and/or paramedics (93.5%) were consulted.

Palliative sedation is meant to reduce consciousness to treat refractory symptoms in patients with a poor prognosis, without the intention to hasten death. In four cases of palliative sedation only morphine was used, without any sedatives; this demonstrates the need for (further) education on this topic as this is not considered good practice.

Opioids alone are not considered a gold standard for sedation due to their other side effects. For palliative sedation, the use of benzodiazepines or sedatives is preferred.²⁷

In this study, an explicit intention to hasten death was reported in six cases. In 36 patients, according to the report by the physician who filled out the document, the doses of opioids/sedatives were not strictly proportional to the symptoms (administration of opioids/sedatives could have hastened death). In these cases, sedation could therefore be seen as a medical alternative for euthanasia, without knowing the patient's wishes and without formal registration. This practice poses ethical problems, leads to confusing and problematic care, and may be considered inappropriate, possibly even more so in countries without mandatory registration of euthanasia.²²

Official national and international guidelines for sedation exist.^4,12 However, in contrast to the mandatory registration of euthanasia, the registration of palliative sedation is not required by law in Belgium. Registration of palliative sedation only exists as a mandatory law in Canada: physicians must obtain written informed consent from patients or their representatives before initiating any form of palliative sedation, irrespective of its expected depth or duration.¹⁴ In emergencies, this consent is not required.

In the Belgian Model of Integral End-of-Life Care, where registration of euthanasia is obligatory but registration of palliative sedation is not, the question arises as to whether the aforementioned inappropriate cases could have been avoided by better regulation and mandatory registration. These unregulated practices likewise concern patient autonomy, raise the same ethical issues, and deserve similar precautions to euthanasia.²⁸ Additionally, our pilot study further demonstrated that such mandatory registration is feasible.

A limitation of our study is that our sample did not include any patients who improved after starting palliative sedation and who lived more than 24 hours. This limits our results to instances of continuous sedation until death only, without any included cases of intermittent palliative sedation.

Another limitation was that we did not clearly distinguish between the use of regular sedatives (antianxiety medication and hypnotics) and proportionate palliative sedation (PPS) or palliative sedation to unconsciousness (PSU).

In PPS, sedating medications (usually benzodiazepines) are used to treat refractory symptoms in terminally ill patients, resulting in increasing levels of sedation during both waking and sleeping hours to help relieve suffering. The minimum dosage of sedatives is used to reduce suffering to a level that is acceptable to the patient.²⁹

In PSU, unconsciousness is the intended goal of therapy. It is performed in patients whose death is imminent to treat severe physical symptoms that are intolerable despite state-of-the-art palliative care, where continuing consciousness under the circumstances is unacceptable.²⁹

Conclusion

The intention of formal registration of palliative sedation is to obtain good clinical practice, where patients receive the most appropriate end-of-life care, avoiding abusive and injudicious or unskilled use of sedation or “slow” euthanasia.

An additional purpose of registration could potentially be to study and review all such cases of palliative sedation, to learn about indications, practice patterns, and outcomes.

The results of our study show that objective registration of palliative sedation is called for in the Belgian Model of Integral End-of-Life Care. Furthermore, to avoid questionable end-of-life decisions, it is important that all caregivers are aware of the correct protocol for each end-of-life decision. A dedicated palliative support team can play a crucial role in this process, not only by providing the proper care for the patient, but also by providing caregiver training to ensure best practices and overall compliance to ethical standards.

Footnotes

Funding Information

No funding was received for this article.

Author Disclosure Statement

No competing financial interests exist.

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