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Drugs Used for Euthanasia: A Repeated Population-Based Mortality Follow-Back Study in Flanders, Belgium, 1998–2013

Open ArchivePublished:July 15, 2018DOI:https://doi.org/10.1016/j.jpainsymman.2018.06.015

      Abstract

      Context

      According to guideline recommendations, barbiturates and neuromuscular relaxants are the recommended drugs for euthanasia.

      Objectives

      To describe changes over time in drugs used to perform euthanasia and differences in case characteristics according to the drugs used.

      Methods

      Repeated population-based mortality follow-back study among physicians attending a large representative sample of deaths in 1998, 2007, and 2013 in Flanders, Belgium.

      Results

      In 1998, we identified 25 euthanasia cases (1.2% of all deaths), 142 cases in 2007 (2.0% of all deaths), and 349 cases in 2013 (4.6% of all deaths). Use of recommended drugs to perform euthanasia increased from 11.9% of euthanasia cases in 1998 to 55.3% in 2007 and 66.8% in 2013 (P < 0.001). In 2013, cases with recommended drugs compared with nonrecommended drugs more often involved requests expressed both orally and in writing (86.8%/14.1%; P < 0.001), consultation with colleague physicians (93.8%/69.1%; P < 0.001), and administration in the presence of another physician (98.3%/54.3%; P < 0.001), and were more often self-labeled by physicians as euthanasia (95.5%/0.9%; P < 0.001) and reported to the euthanasia review committee (92.3%/3.8%; P < 0.001). Between 2007 and 2013, physicians consistently labeled cases in which nonrecommended drugs were used as palliative sedation (72.8%/78.4%; P = 0.791) or alleviation of pain and symptoms (13.2%/15.0%; P > 0.999).

      Conclusion

      Physicians in Flanders are increasingly using the recommended drugs for euthanasia. This suggests that guidelines and training regarding the conduct and pharmacological aspects of euthanasia may have had important effects on the practice of euthanasia. However, the declining but persisting use of nonrecommended drugs requires further attention.

      Key Words

      Introduction

      In 2002, euthanasia, that is termination of life by a physician at the patient's explicit request, became a legal possibility at the end of life in Belgium.
      Belgian Official Collection of the Laws
      The Belgian Act on Euthanasia of May, 28th 2002.
      Strict due care and procedural criteria are specified in the law to regulate the practice. The Belgian euthanasia law states that euthanasia should be performed by a physician.
      Belgian Official Collection of the Laws
      The Belgian Act on Euthanasia of May, 28th 2002.
      It does not specify which drugs physicians should use to end the patient's life as therapeutic freedom is strongly defended by the medical professional associations. The Belgian professional association for pharmacists has clarified which products and materials are needed to perform euthanasia.
      • Schaus V.
      The recommended procedure is to administer a barbiturate overdose, optionally followed by a neuromuscular relaxant to induce respiratory arrest.
      • Schaus V.
      Optionally, the physician can administer a benzodiazepine (midazolam) to induce sleep before administering the barbiturate. The Belgian guideline is broadly similar to the Dutch guideline issued by the Royal Dutch Medical Association.

      KNMG/KNMP Guideline Performance of euthanasie and physician-assisted suicide [in Dutch]. 2012.

      However, the Dutch guideline states that a neuromuscular relaxant should always be administered, even if the patient seems to be deceased after administering the barbiturate. Other drugs such as opioids and benzodiazepines or combinations of these drugs without the use of a barbiturate and/or a neuromuscular relaxant are explicitly advised against in the Dutch guideline because of the uncertain lethal effect and adverse side effects.

      KNMG/KNMP Guideline Performance of euthanasie and physician-assisted suicide [in Dutch]. 2012.

      • Sykes N.
      • Thorns A.
      The use of opioids and sedatives at the end of life.
      Barbiturates are also the preferred drugs in Switzerland and some U.S. states where physician-assisted suicide is legal.
      • Bosshard G.
      • Ulrich E.
      • Bär W.
      748 cases of suicide assisted by a Swiss right-to-die organisation.
      • Fass J.
      • Fass A.
      Physician-assisted suicide: ongoing challenges for pharmacists.
      In Canada, the most common protocol for euthanasia is midazolam followed by propofol and a neuromuscular relaxant.
      • Wiebe E.
      • Green S.
      • Schiff B.
      Teaching residents about medical assistance in dying.
      The Belgian professional association for pharmacists has additionally provided instructions on the equipment needed to perform euthanasia by infusion or injection.
      • Schaus V.
      Information and best practices regarding the euthanasia procedure, including its performance, are also disseminated by the Life's End Information Forum (LEIF) in Flanders, the northern Dutch-speaking part of Belgium. This forum was established in the year following the enactment of the Belgian Euthanasia Law in September 2002.
      • Van Wesemael Y.
      • Cohen J.
      • Bilsen J.
      • et al.
      Implementation of a service for physicians' consultation and information in euthanasia requests in Belgium.
      LEIF is a consultation service that aims to inform, assist, and train physicians in end-of-life care and specifically euthanasia.
      • Van Wesemael Y.
      • Cohen J.
      • Bilsen J.
      • et al.
      Implementation of a service for physicians' consultation and information in euthanasia requests in Belgium.
      • Van Wesemael Y.
      • Cohen J.
      • Onwuteaka-Philipsen B.D.
      • et al.
      Role and involvement of life end information forum physicians in euthanasia and other end-of-life care decisions in Flanders, Belgium.
      Once the physician has assessed all due care criteria and is convinced that euthanasia can be granted for the competent patient, it is important that the correct drugs to perform euthanasia are chosen. Failure to do so may lead to traumatic situations such as an extended time to death or awakening of the patient,
      • Groenewoud J.H.
      • van der Heide A.
      • Onwuteaka-Philipsen B.D.
      • et al.
      Clinical problems with the performance of euthanasia and physician-assisted suicide in The Netherlands.
      • Horikx A.
      • Admiraal P.V.
      Utilization of euthanatic agents: experience of physicians with 227 patients, 1998-2000 (in Dutch).
      causing distress for the patient and the attending family and health care providers. Previous studies have shown that drugs that are advised against, that is, opioids and sedatives, are used to perform euthanasia
      • Smets T.
      • Bilsen J.
      • Cohen J.
      • et al.
      Reporting of euthanasia in medical practice in Flanders, Belgium: cross sectional analysis of reported and unreported cases.
      • Vander Stichele R.
      • Bilsen J.
      • Bernheim J.L.
      • Mortier F.
      • Deliens L.
      Drugs used for euthanasia in Flanders, Belgium.
      and that these drugs are used in some euthanasia cases that remain unreported to the euthanasia review committee.
      • Smets T.
      • Bilsen J.
      • Cohen J.
      • et al.
      Reporting of euthanasia in medical practice in Flanders, Belgium: cross sectional analysis of reported and unreported cases.
      The present study reports on the drugs used for euthanasia in Flanders, Belgium. The aims of this study are 1) to describe which drugs are used to perform euthanasia, and how this has changed since before the euthanasia law, 2) to describe euthanasia case characteristics (decision-making and administrative characteristics, physicians' perceptions of their act, and reporting) in relation to the types of drugs used to perform euthanasia, and 3) to describe time trends in euthanasia case characteristics in relation to drugs used to perform euthanasia.

      Methods

      Study Design

      We compare data from large-scale population-based mortality follow-back surveys on medical end-of-life decision making conducted in Flanders (the Dutch-speaking northern half of Belgium) in 1998, 2007, and 2013, that is, respectively, four years before, five years after, and 11 years after the introduction of euthanasia legislation in Belgium. All studies are based on a large and representative sample of deaths using the same sampling and data collection method. The Flemish Agency for Care and Health selected a random stratified sample of all death certificates of people aged one year or older within the study period. Attending physicians for these death certificates were requested to complete a questionnaire by mail about the end-of-life care and decision making while consulting the patient's medical file. To guarantee absolute anonymity for participating physicians, a lawyer served as an intermediary between responding physicians, researchers, and the Flemish Agency for Care and Health. The Ethical Review Board of the University Hospital of the Vrije Universiteit Brussel (VUB), the Belgian National Disciplinary Board of Physicians, and the Belgian Privacy Commission approved the mailing and anonymity procedure. The study design, sampling, and mailing procedure are described in detail elsewhere.
      • Chambaere K.
      • Bilsen J.
      • Cohen J.
      • et al.
      A post-mortem survey on end-of-life decisions using a representative sample of death certificates in Flanders, Belgium: research protocol.
      • Deliens L.
      • Mortier F.
      • Bilsen J.
      • et al.
      End-of-life decisions in medical practice in Flanders, Belgium: a nationwide survey.
      • Bilsen J.
      • Cohen J.
      • Chambaere K.
      • et al.
      Medical end-of-life practices under the euthanasia law in Belgium.
      • Chambaere K.
      • Vander Stichele R.
      • Mortier F.
      • Cohen J.
      • Deliens L.
      Recent trends in euthanasia and other end-of-life practices in Belgium.
      A similar study was also performed in 2001, during a period in which the euthanasia debate reached its culmination point, eventually leading to the legalization of euthanasia in 2002.
      • Bilsen J.
      • Vander Stichele R.
      • Broeckaert B.
      • Mortier F.
      • Deliens L.
      Changes in medical end-of-life practices during the legalization process of euthanasia in Belgium.
      Because of the potential bias related to conducting the study during the euthanasia legalization process, such as socially desirable answers, and the limited number of euthanasia cases (n = 18), data for 2001 are not included in the analyses.

      Questionnaire

      The questionnaire first asked whether the death of the patient had been sudden and unexpected. If the answer was negative, physicians were asked about the medical decisions made at the end of the patient's life with a possible or certain life-shortening effect. We identified cases as euthanasia if the physician gave an affirmative answer to the following questions: 1) was the death the consequence of the use of drugs prescribed, supplied, or administered by you or another physician with the explicit intention of hastening the end of life or of enabling the patient to end his or her own life? 2) Was the decision made at the explicit request of the patient?
      In the 1998 questionnaire, physicians were asked to specify in writing which drugs were used. In 2007 and 2013, physicians were asked to indicate prestructured response categories, which were 1) neuromuscular relaxant (curare or similar drug), 2) barbiturate, 3) benzodiazepine, 4) morphine or other opioid, and 5) other drug, with the possibility to specify the other drug in writing. Multiple answers were possible for this question. Physicians were also asked to indicate who administered the drugs by multiple choice, that is, 1) the patient, 2) you or another physician, 3) a nurse, and 4) someone else, with the possibility to specify in writing. For this question also, multiple answers were possible.
      In addition, we asked for the estimated time by which the patient's life was shortened, the manner in which the patient expressed the euthanasia request, whether the decision was discussed with others, how they would label the end-of-life act, whether they reported the act to the euthanasia review committee, and, if not reported to the committee, the reason(s) for not reporting.

      Statistical Analysis

      Data were weighted to correct for the disproportionate stratification of deaths and adjusted to be representative of all deaths in the period covered by the surveys in terms of age, sex, marital status, province of death, cause of death, and place of death.
      We dichotomized the categories in which drugs used to perform euthanasia were categorized, reflecting the recommended drugs to perform euthanasia according to the guideline of the Belgian Professional Association for pharmacists.
      • Schaus V.
      The first category, recommended drugs, includes barbiturates and neuromuscular relaxants, barbiturates used alone or with other drugs (excluding neuromuscular relaxants), and neuromuscular relaxants used alone or with other drugs (excluding barbiturates). The second category, nonrecommended drugs, includes benzodiazepines and opioids, benzodiazepines used alone or with other drugs (excluding barbiturates, neuromuscular relaxants, or opioids), opioids used alone or with other drugs (excluding barbiturates, neuromuscular relaxants, or benzodiazepines), and other drugs.
      Physician-assisted suicide, that is when patients administer the lethal drugs themselves, is treated as a form of euthanasia by the Belgian Euthanasia Review Committee, although it is not mentioned in the euthanasia law. Cases of physician-assisted suicide are subject to the same due care criteria as cases of euthanasia. Therefore, cases of physician-assisted suicide were included in the analysis as cases of euthanasia.
      We carried out Pearson's Chi-squared tests and Fisher exact tests to analyze differences between recommended and nonrecommended drugs in euthanasia case characteristics. We also carried out Pearson's Chi-squared tests and Fisher exact tests to identify trends in the nature of drugs used to perform euthanasia.

      Results

      In 1998, we identified 25 euthanasia cases (1.2% of all deaths); in 2007, we identified 142 cases (2.0% of all deaths); and in 2013, we identified 349 cases (4.6% of all deaths) in Flanders, Belgium (Table 1).
      Table 1Characteristics of Deaths by Euthanasia in Flanders, Belgium, in 1998, 2007, and 2013
      Characteristics199820072013
      Total number of deaths (unweighted)192536233751
      Number of euthanasia deaths (unweighted)
      Numbers include three cases of physician-assisted suicide in 1998, five cases in 2007, and six cases in 2013. Physician-assisted suicide, that is when patients administer the lethal drugs themselves, is treated as a form of euthanasia by the Belgian Euthanasia Review Committee, although it is not mentioned in the euthanasia law.
      25142349
      Percentage of all euthanasia deaths (weighted)1.22.04.6
      Sex
       Male40.461.351.0
       Female59.638.749.0
      Age (yrs)
       18–6435.837.018.9
       65–7929.042.637.8
       80 or older35.220.443.2
      Cause of death
       Cardiovascular disease
      Includes cerebrovascular disease.
      14.13.814.3
       Malignancies46.180.257.4
       Respiratory disease11.14.74.1
       Disease of the nervous system7.67.27.4
       Other disease21.14.016.9
      Place of death
       At home48.443.141.8
       Hospital43.151.342.5
       Care home8.65.615.6
       Other0.00.00.1
      Weighted row percentages.
      a Numbers include three cases of physician-assisted suicide in 1998, five cases in 2007, and six cases in 2013. Physician-assisted suicide, that is when patients administer the lethal drugs themselves, is treated as a form of euthanasia by the Belgian Euthanasia Review Committee, although it is not mentioned in the euthanasia law.
      b Includes cerebrovascular disease.

      Type of Drugs Used to Perform Euthanasia and Time Trends

      The use of recommended drugs increased from 11.9% in 1998 to 55.3% in 2007 and 66.8% in 2013 (P < 0.001) (Table 2). Barbiturates combined with neuromuscular relaxants were the recommended drugs most often used in 2013 (39.7%). Nonrecommended drugs were decreasingly used, from 88.1% of all cases in 1998 to 44.7% in 2007 and 33.2% in 2013. Opioids only or with other drugs (excluding barbiturate, neuromuscular relaxant, or benzodiazepine) were the most often used nonrecommended drugs in 2013 (16.0%).
      Table 2Trends in Drugs Used to Perform Euthanasia, in 1998, 2007, and 2013
      Drugs Used199820072013P
      P-values calculated with Pearson's Chi-squared test.
      Unweighted number of cases25142349
       Recommended drugs
      • Schaus V.

      KNMG/KNMP Guideline Performance of euthanasie and physician-assisted suicide [in Dutch]. 2012.

      11.955.366.8<0.001
       Barbiturates and neuromuscular relaxants4.830.139.70.009
       Barbiturates only or with other drugs (excluding neuromuscular relaxants)7.115.420.10.258
       Neuromuscular relaxants only or with other drugs (excluding barbiturates)0.09.87.1
      P-value could not be calculated because of low cell frequencies.
      Nonrecommended drugs

      KNMG/KNMP Guideline Performance of euthanasie and physician-assisted suicide [in Dutch]. 2012.

      88.144.733.2<0.001
       Benzodiazepines and opioids17.520.914.80.469
       Benzodiazepines only or with other drugs (excluding barbiturate, neuromuscular relaxant, or opioid)9.60.51.8
      P-value could not be calculated because of low cell frequencies.
       Opioids only or with other drugs (excluding barbiturate, neuromuscular relaxant, or benzodiazepine)61.123.316.0<0.001
       Other0.00.00.5
      P-value could not be calculated because of low cell frequencies.
      Weighted column percentages. Missing values: 1998: n = 5; 2007: n = 2; and 2013: n = 11.
      a P-values calculated with Pearson's Chi-squared test.
      b P-value could not be calculated because of low cell frequencies.

      Decision-Making and Administration Characteristics, Estimated Degree of Life Shortening, Labeling, and Reporting of Euthanasia Cases According to the Type of Drugs Used to Perform Euthanasia in 2013

      Where recommended drugs were used, compared with cases where nonrecommended drugs were used, the request for euthanasia was more often expressed both orally and in writing (86.8%/14.1%; P < 0.001) and less often only orally (5.7%/80.5%; P < 0.001). There was more often discussion with a fellow physician when recommended drugs were used (93.8%/69.1%; P < 0.001). Recommended drugs were more often administered by a physician only (93.7%/25.2%; P < 0.001) and less often by a nurse only (1.5%/41.5%; P < 0.001). A physician was more often present during the administration of recommended drugs (98.3%/54.3%; P < 0.001). If recommended drugs were used, the estimated degree of life shortening was less often 24 hours or less (8.3%/21.1%; P = 0.024) or one to seven days (33.3%/58.6%; P = 0.003), and physicians more often estimated that the patient's life was shortened by more than one week (57.8/16.7%; P < 0.001) (Table 3). In cases with recommended drugs, the physician more often labeled the act as euthanasia (95.5%/0.9%; P < 0.001) and less often as palliative sedation (4.3%/78.4%; P < 0.001) or alleviation of pain and symptoms (0.0%/15.0%; P < 0.001). Euthanasia cases were more frequently reported to the Federal Control and Evaluation Committee when recommended drugs were used (92.3%/3.8%; P < 0.001).
      Table 3Decision-Making and Administration Characteristics, Labeling, and Reporting of Euthanasia Cases in Relation to Drugs Used to Perform Euthanasia, 2013
      CharacteristicsAll CasesDrugs Used to Perform Euthanasia
      RDNRDP
      P-values calculated with Fisher exact test.
      Unweighted number of cases34927264
      Type of request
       Only oral30.55.780.5<0.001
       Only in writing1.21.90.00.549
       Oral and in writing62.886.814.1<0.001
       Advance euthanasia directive5.55.75.4>0.999
      Decision discussed with others
      Multiple answers possible.
       Another physician85.693.869.1<0.001
       Caregiver specialized in palliative care52.453.550.30.743
       Nursing staff54.954.852.90.869
       Relative81.380.981.8>0.999
      Person who administered the drugs
       Only physician71.493.725.2<0.001
       Only nurse14.71.441.5<0.001
       Physician and other person(s)
      Other persons were a nurse and/or the patient.
      12.44.529.0<0.001
       Nurse and other person(s) (excluding physician)
      Other persons were a palliative care team.
      0.60.02.00.327
       Only other person(s)
      Other persons were the patient with or without a palliative care team.
      0.90.22.20.327
       Physician present during administration83.798.354.3<0.001
      Estimated degree of life shortening
       Probably none1.70.63.60.261
       Less than 24 hours12.58.321.10.024
       One to seven days41.033.358.60.003
       More than one week44.857.816.7<0.001
      Label given by the physician
       Euthanasia64.695.50.9<0.001
       Palliative or terminal sedation28.54.378.4<0.001
       Alleviation of pain and symptoms4.90.015.0<0.001
       Compassionate life ending0.80.12.20.337
       Other1.20.13.50.110
      Reporting to the euthanasia review committee
       Reported63.592.33.8<0.001
       Not reported because
      Multiple answers possible.
      Not euthanasia according to the physician30.83.893.60.001
      Administrative burden1.91.72.50.052
      Matter between physician and patient1.71.62.10.052
      Possibly not all legal criteria adhered to0.00.00.0>0.999
      Possible judicial consequences1.10.62.50.272
      Percentages are weighted column percentages. Missing values for drugs used to perform euthanasia: n = 13.
      RD = recommended drugs (barbiturates and/or neuromuscular relaxants); NRD = nonrecommended drugs (opioids, benzodiazepines, or other drugs other than barbiturates or neuromuscular relaxants).
      a P-values calculated with Fisher exact test.
      b Multiple answers possible.
      c Other persons were a nurse and/or the patient.
      d Other persons were a palliative care team.
      e Other persons were the patient with or without a palliative care team.

      Trends in Decision-Making and Administration Characteristics, Estimated Degree of Life Shortening, Labeling, and Reporting of Euthanasia Cases According to the Type of Drugs Used Between 1998, 2007, and 2013

      Where recommended drugs were used, in 2013 compared with 2007, euthanasia requests were increasingly expressed both orally and in writing (from 66.9% in 2007 to 86.8% in 2013; P = 0.026) and decreasingly only orally (from 24.4% in 2007 to 5.7% in 2013; P = 0.003) (Table 4). The presence of a physician during administration of the drugs remained consistent (99.0% in 2007/98.3% in 2013; P > 0.999) as well as reporting to the euthanasia review committee (92.0% in 2007/92.3% in 2013; P > 0.999).
      Table 4Trends in Decision-Making and Administration Characteristics, Labeling, and Reporting of Euthanasia Cases in Relation to Drugs Used to Perform Euthanasia, in 1998, 2007, and 2013
      CharacteristicsAll CasesRecommended Drugs
      Recommended drugs: barbiturates and/or neuromuscular relaxants.
      Nonrecommended Drugs
      Nonrecommended drugs: opioids, benzodiazepines, or other drugs other than barbiturates or neuromuscular relaxants.
      199820072013P
      P-values calculated with Fisher exact test (type of request, label given by physician, reporting to the euthanasia review committee) or Pearson's Chi-squared test (decision discussed with others, person who administered the drugs, physician present during administration, estimated degree of life shortening).
      199820072013P
      P-values calculated with Fisher exact test (type of request, label given by physician, reporting to the euthanasia review committee) or Pearson's Chi-squared test (decision discussed with others, person who administered the drugs, physician present during administration, estimated degree of life shortening).
      199820072013P
      P-values calculated with Fisher exact test (type of request, label given by physician, reporting to the euthanasia review committee) or Pearson's Chi-squared test (decision discussed with others, person who administered the drugs, physician present during administration, estimated degree of life shortening).
      Unweighted number of cases25142349287272185364
      Type of request
       Only oral
      Data for 1998 are not available as these questions were not included in the survey.
      50.130.50.005
      Data for 1998 are not available as these questions were not included in the survey.
      24.45.70.003
      Data for 1998 are not available as these questions were not included in the survey.
      84.280.50.779
       Only in writing
      Data for 1998 are not available as these questions were not included in the survey.
      6.41.20.025
      Data for 1998 are not available as these questions were not included in the survey.
      8.71.90.109
      Data for 1998 are not available as these questions were not included in the survey.
      3.80.00.356
       Oral and in writing
      Data for 1998 are not available as these questions were not included in the survey.
      43.162.80.010
      Data for 1998 are not available as these questions were not included in the survey.
      66.986.80.026
      Data for 1998 are not available as these questions were not included in the survey.
      11.014.10.739
       Advance euthanasia directive
      Data for 1998 are not available as these questions were not included in the survey.
      0.55.50.061
      Data for 1998 are not available as these questions were not included in the survey.
      0.05.70.339
      Data for 1998 are not available as these questions were not included in the survey.
      1.15.40.550
      Decision discussed with others
      Multiple answers are possible.
       Another physician48.977.885.6<0.00110097.493.80.68060.552.569.10.109
       Caregiver specialized in palliative care
      Data for 1998 are not available as these questions were not included in the survey.
      50.052.40.779
      Data for 1998 are not available as these questions were not included in the survey.
      65.153.50.190
      Data for 1998 are not available as these questions were not included in the survey.
      31.350.30.121
       Nursing staff30.954.154.90.08559.85454.8>0.99938.754.552.9>0.999
       Relative61.677.481.30.10610078.980.9>0.99979.776.881.80.587
      Person who administered the drugs
       Only physician54.669.271.40.24810094.593.7>0.99964.837.325.20.213
       Only nurse6.719.114.70.4590.00.01.4>0.99910.143.141.5>0.999
       Physician and other person(s)
      Other persons were a nurse, the patient, and/or the patient's relative.
      14.010.612.40.8880.04.54.5>0.99921.118.5290.444
       Nurse and other person(s) (excluding physician)
      Other persons were a palliative team.
      0.00.00.60.00.00.0>0.9990.00.02.0>0.999
       Only other person(s)
      Other persons were a palliative care team and/or the patient.
      24.8
      These are four cases in which the palliative care team and one case in which the patient administered the drugs.
      1.00.9<0.0010.010.2>0.9994.01.12.2>0.999
       Physician present during administration68.680.183.72541009998.3>0.99985.955.854.3>0.999
      Estimated degree of life shortening
       Probably none3.61.71.70.6840.00.00.6>0.9995.43.83.6>0.999
       Less than 24 hours18.39.712.50.6790.04.08.30.45223.317.121.10.585
       One to seven days60.144.141.00.2650.036.333.30.68957.555.458.60.823
       More than one week18.044.544.80.02910059.757.8>0.99913.723.616.70.567
      Label given by the physician
       Euthanasia
      Data for 1998 are not available as these questions were not included in the survey.
      54.364.60.192
      Data for 1998 are not available as these questions were not included in the survey.
      92.695.5>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      4.70.90.356
       Palliative or terminal sedation
      Data for 1998 are not available as these questions were not included in the survey.
      34.128.50.443
      Data for 1998 are not available as these questions were not included in the survey.
      4.14.3>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      72.878.40.791
       Alleviation of pain and symptoms
      Data for 1998 are not available as these questions were not included in the survey.
      6.14.90.750
      Data for 1998 are not available as these questions were not included in the survey.
      0.50.0>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      13.215.0>0.999
       Compassionate life ending
      Data for 1998 are not available as these questions were not included in the survey.
      0.40.8>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      0.80.1>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      0.02.2>0.999
       Other
      Data for 1998 are not available as these questions were not included in the survey.
      5.11.20.062
      Data for 1998 are not available as these questions were not included in the survey.
      2.00.10.253
      Data for 1998 are not available as these questions were not included in the survey.
      9.33.50.343
      Reporting to the euthanasia review committee
       Reported
      Data for 1998 are not available as these questions were not included in the survey.
      53.763.50.194
      Data for 1998 are not available as these questions were not included in the survey.
      9292.3>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      4.53.8>0.999
      Not reported because
      Multiple answers are possible.
       Not euthanasia according to the physician
      Data for 1998 are not available as these questions were not included in the survey.
      36.130.80.189
      Data for 1998 are not available as these questions were not included in the survey.
      1.13.80.236
      Data for 1998 are not available as these questions were not included in the survey.
      83.593.60.135
       Administrative burden
      Data for 1998 are not available as these questions were not included in the survey.
      9.51.90.030
      Data for 1998 are not available as these questions were not included in the survey.
      41.70.547
      Data for 1998 are not available as these questions were not included in the survey.
      172.50.025
       Matter between physician and patient
      Data for 1998 are not available as these questions were not included in the survey.
      5.21.70.241
      Data for 1998 are not available as these questions were not included in the survey.
      3.91.6>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      7.12.10.552
       Possibly not all legal criteria adhered to
      Data for 1998 are not available as these questions were not included in the survey.
      6.10.00.014
      Data for 1998 are not available as these questions were not included in the survey.
      6.30.00.055
      Data for 1998 are not available as these questions were not included in the survey.
      6.20.00.136
       Possible judicial consequences
      Data for 1998 are not available as these questions were not included in the survey.
      2.11.1>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      10.6>0.999
      Data for 1998 are not available as these questions were not included in the survey.
      3.82.5>0.999
      Percentages are weighted column percentages. Missing values for drugs used to perform euthanasia: 1998: n = 5; 2007: n = 2; and 2013: n = 11.
      a Recommended drugs: barbiturates and/or neuromuscular relaxants.
      b Nonrecommended drugs: opioids, benzodiazepines, or other drugs other than barbiturates or neuromuscular relaxants.
      c P-values calculated with Fisher exact test (type of request, label given by physician, reporting to the euthanasia review committee) or Pearson's Chi-squared test (decision discussed with others, person who administered the drugs, physician present during administration, estimated degree of life shortening).
      d Data for 1998 are not available as these questions were not included in the survey.
      e Multiple answers are possible.
      f Other persons were a nurse, the patient, and/or the patient's relative.
      g Other persons were a palliative team.
      h Other persons were a palliative care team and/or the patient.
      i These are four cases in which the palliative care team and one case in which the patient administered the drugs.
      Where nonrecommended drugs were used, administrative burden (having to report the euthanasia case to the euthanasia review committee) was decreasingly indicated as a reason not to report the case to the committee (from 17.0% in 2007 to 2.5% in 2013; P = 0.025). Physicians consistently labeled cases in which nonrecommended drugs were used as palliative sedation (72.8% in 2007/78.4% in 2013; P = 0.791) or alleviation of pain and symptoms (13.2% in 2007/15.0% in 2013; P > 0.999). The presence of a physician during administration of the drugs remained stable (55.8% in 2007/54.3% in 2013; P > 0.999) as well as reporting to the euthanasia review committee (4.5% in 2007/3.8% in 2013; P > 0.999).

      Discussion

      Main Findings

      This study found that the recommended drugs, that is barbiturates and/or neuromuscular relaxants, were increasingly used to perform euthanasia, from 11.9% of euthanasia cases in 1998 to 55.3% in 2007 and 66.8% in 2013. The use of nonrecommended drugs, especially opioids and/or benzodiazepines, decreased from 88.1% in 1998 to 44.7% in 2007 and 33.2% in 2013. Cases where the recommended drugs were used more often involved a request that was expressed both orally and in writing, consultation with colleague physicians, and administration in the presence of a physician, and were more often self-labeled by physicians as euthanasia and reported to the euthanasia review committee.

      Strengths and Weaknesses of This Study

      By taking a population-based approach, we are able to report representative data on euthanasia case characteristics across care settings and diagnoses. In addition, by repeatedly using a similar study design, sampling, and mailing procedure, we can make reliable comparisons over time. However, our study also has some limitations. The study does not allow an in-depth analysis of the drugs that were administered, for example, information on drug doses was not gathered in all the years studied. Furthermore, as we used a retrospective survey study design, recall bias cannot be excluded. Physicians were however asked to consult the patient's medical file while completing the questionnaire to reduce recall bias. The sensitivity of the survey topic may have introduced the possibility of untruthful or socially desirable reporting, but this is likely negligible given the explicit guarantee of anonymity and the avoidance of the term euthanasia in the survey itself. Finally, as the 1998 sample included a small number of euthanasia cases, the possibility of Type II errors, that is false negatives, cannot be excluded.

      Meaning of the Findings and Comparison With Other Studies

      We found that the recommended drugs for performing euthanasia, that is barbiturates and/or neuromuscular relaxants, were increasingly used after the introduction of euthanasia legislation in 2002. Before euthanasia legislation, drugs that are considered unsuitable for euthanasia and that are therefore advised against, especially morphine, were used in most cases. After legalization of euthanasia, recommended drugs, that is barbiturates and/or neuromuscular relaxants, were increasingly used. Numbers from the Federal Control and Evaluation Committee for Euthanasia on reported cases show the same trend of recommended drugs being increasingly used to perform euthanasia.
      • Dierickx S.
      • Deliens L.
      • Cohen J.
      • Chambaere K.
      Euthanasia in Belgium: trends in reported cases between 2003 and 2013.

      Federale Controle- en Evaluatiecommissie Euthanasie. Zevende verslag aan de wetgevende kamers, jaren 2014-2015. 2016.

      This suggests that since the introduction of euthanasia legislation, physicians have become increasingly familiar with recommended euthanasia procedure. Dissemination to physicians of best practices for euthanasia, for instance by LEIF,
      • Van Wesemael Y.
      • Cohen J.
      • Bilsen J.
      • et al.
      Implementation of a service for physicians' consultation and information in euthanasia requests in Belgium.
      and providing training and information to clinicians through media dissemination and exchanges of experiences among professionals in a context that is increasingly open to the topic of euthanasia may have played a significant role in the increase in adoption of the guidelines. Population-based studies in The Netherlands, where euthanasia was also legalized in 2002, have also found that the recommended drugs for euthanasia are increasingly used and that most cases of euthanasia are undertaken with barbiturates and/or neuromuscular relaxants.
      • Onwuteaka-Philipsen B.D.
      • Brinkman-Stoppelenburg A.
      • Penning C.
      • et al.
      Trends in end-of-life practices before and after the enactment of the euthanasia law in The Netherlands from 1990 to 2010: a repeated cross-sectional survey.
      • Rurup M.L.
      • Onwuteaka-Philipsen B.D.
      • van der Heide A.
      • van der Wal G.
      • van der Maas P.J.
      Trends in the agents used for euthanasia and the relationship with the number of notifications (in Dutch).
      Recommended drugs are however more frequently used in The Netherlands (in 80% of euthanasia or physician-assisted suicide cases in 2010
      • Onwuteaka-Philipsen B.D.
      • Brinkman-Stoppelenburg A.
      • Penning C.
      • et al.
      Trends in end-of-life practices before and after the enactment of the euthanasia law in The Netherlands from 1990 to 2010: a repeated cross-sectional survey.
      ) than in Flanders, Belgium. This may be related to a longer experience and open societal and medical debate about good euthanasia practice, going back to as early as 1987 when the first guideline on the medicotechnical aspects of euthanasia was issued in The Netherlands, before the practice was formally legalized.

      KNMG/KNMP Guideline Performance of euthanasie and physician-assisted suicide [in Dutch]. 2012.

      Despite the observed decrease in nonrecommended drugs to perform euthanasia, one-third of cases identified in this study in 2013 still involved the use of nonrecommended drugs, mainly opioids or benzodiazepines, to intentionally hasten death on patient request. Some physicians may overestimate the actual lethal effect of these drugs in persons at the very end of life.
      • Sykes N.
      • Thorns A.
      The use of opioids and sedatives at the end of life.
      • Sykes N.
      • Thorns A.
      Sedative use in the last week of life and the implications for end-of-life decision making.
      • Azoulay D.
      • Jacobs J.M.
      • Cialic R.
      • Mor E.E.
      • Stessman J.
      Opioids, survival, and advanced cancer in the hospice setting.
      • Maltoni M.
      • Pittureri C.
      • Scarpi E.
      • et al.
      Palliative sedation therapy does not hasten death: results from a prospective multicenter study.
      Another possible explanation is that some physicians use drugs that are not associated with the recommended euthanasia procedure but with palliative sedation as a strategy to reduce cognitive dissonance, that is the mental discomfort experienced by a person with conflicting attitudes, as some clinicians find palliative sedation emotionally less burdensome to perform than euthanasia.
      • Rietjens J.A.C.
      • Buiting H.M.
      • Pasman H.R.W.
      • et al.
      Deciding about continuous deep sedation: physicians' perspectives: a focus group study.
      Also, physicians may intend to hasten death without using the established procedures that make it an obvious euthanasia case but by increasing medication for sedation or pain and symptom control to avoid lengthy procedures, due care requirements, or the administrative burden of reporting to the review committee. In these cases, the requirements for due care are significantly less often adhered to than in cases in which recommended drugs were used: there was more often only an oral request, a colleague physician was less often consulted, and the euthanasia was more often carried out in the absence of a physician.
      Furthermore, these cases are generally not reported to the committee and thus not reviewed, mainly because physicians did not consider the case as euthanasia. Studies in The Netherlands also show that nonreporting of euthanasia is strongly related to the type of drugs used.
      • van der Heide A.
      • Onwuteaka-Philipsen B.D.
      • Rurup M.L.
      • et al.
      End-of-life practices in The Netherlands under the euthanasia act.
      These nonreported cases are usually considered as palliative sedation or intensified alleviation of pain and symptoms by the attending physicians. Flemish physicians seem to use a fairly narrow definition of euthanasia based on the drugs used and legal procedures. What is not performed with these drugs or is not in accordance with the legal procedures, is not euthanasia in their eyes, but rather a gray zone that they label as palliative sedation. Our findings corroborate previous studies identifying this gray zone.
      • Smets T.
      • Bilsen J.
      • Cohen J.
      • et al.
      Reporting of euthanasia in medical practice in Flanders, Belgium: cross sectional analysis of reported and unreported cases.
      • Onwuteaka-Philipsen B.D.
      • Brinkman-Stoppelenburg A.
      • Penning C.
      • et al.
      Trends in end-of-life practices before and after the enactment of the euthanasia law in The Netherlands from 1990 to 2010: a repeated cross-sectional survey.
      • van der Heide A.
      • Onwuteaka-Philipsen B.D.
      • Rurup M.L.
      • et al.
      End-of-life practices in The Netherlands under the euthanasia act.
      • Smets T.
      • Cohen J.
      • Bilsen J.
      • et al.
      The labelling and reporting of euthanasia by Belgian physicians: a study of hypothetical cases.
      • Rurup M.L.
      • Buiting H.M.
      • Pasman H.R.W.
      • et al.
      The reporting rate of euthanasia and physician-assisted suicide: a study of the trends.
      Although some framework papers make a strict distinction between euthanasia and palliative sedation in terms of physicians' intention and the outcome of the act,
      • Cherny N.I.
      • Radbruch L.
      European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care.
      • Abarshi E.
      • Rietjens J.
      • Robijn L.
      • et al.
      International variations in clinical practice guidelines for palliative sedation: a systematic review.
      previous research showed that this distinction is not always clear in clinical practice
      • Anquinet L.
      • Raus K.
      • Sterckx S.
      • et al.
      Similarities and differences between continuous sedation until death and euthanasia—professional caregivers' attitudes and experiences: a focus group study.
      • Rys S.
      • Deschepper R.
      • Mortier F.
      • Deliens L.
      • Bilsen J.
      Bridging the gap between continuous sedation until death and physician-assisted death: a focus group study in nursing homes in Flanders, Belgium.
      • Rietjens J.A.C.
      • Hauser J.
      • van der Heide A.
      • Emanuel L.L.
      Having a difficult time leaving: experiences and attitudes of nurses with palliative sedation.
      • Anquinet L.
      • Rietjens J.A.
      • Van den Block L.
      • Bossuyt N.
      • Deliens L.
      General practitioners' report of continuous deep sedation until death for patients dying at home: a descriptive study from Belgium.
      • Douglas C.
      • Kerridge I.
      • Ankeny R.
      Managing intentions: the end-of-life administration of analgesics and sedatives, and the possibility of slow euthanasia.
      • Foley R.-A.
      • Johnston W.S.
      • Bernard M.
      • et al.
      Attitudes regarding palliative sedation and death hastening among Swiss physicians: a contextually sensitive approach.
      and that some physicians administer sedatives with the intention of hastening death.
      • Rietjens J.A.C.
      • Van Der Heide A.
      • Vrakking A.M.
      • et al.
      Physician reports of terminal sedation without hydration or nutrition for patients nearing death in The Netherlands.
      • Robijn L.
      • Cohen J.
      • Rietjens J.
      • Deliens L.
      • Chambaere K.
      Trends in continuous deep sedation until death between 2007 and 2013: a repeated nationwide survey.
      In half of all euthanasia cases in 2013, the decision to perform euthanasia had been discussed with a palliative care expert. This does not preclude the possibility that palliative care services had been involved outside the euthanasia decision-making procedure. Previously, we have found that palliative care services were involved in 71% of deaths with a euthanasia request.
      • Dierickx S.
      • Deliens L.
      • Cohen J.
      • Chambaere K.
      Involvement of palliative care in euthanasia practice in a context of legalized euthanasia: a population-based mortality follow-back study.
      When no palliative care services had been involved, this had been in more than half of the cases because the existing care already sufficiently addressed the patient's palliative and supportive care needs. Nevertheless, involvement of palliative care experts may increase compliance with guidelines regarding drugs for euthanasia.

      Implications and Recommendations

      The obsolete practice in which benzodiazepines and/or morphine are used to intentionally end a patient's life on patient request requires adequate attention. Despite an increase in euthanasia being performed with drugs recommended by euthanasia guidelines, physicians still use drugs that are advised against, mainly opioids, to hasten death on explicit patient request. These cases remain unreported to the euthanasia review committee because physicians do not consider them to be euthanasia.
      Continuation and further expansion of initiatives aimed at improving health professionals' skills regarding euthanasia performance are recommended. Further education of physicians on euthanasia procedures and the effects and side effects of opioids and sedatives is needed to avoid euthanasia being performed in a way that may be harmful to patients and their relatives and beyond societal control. To further encourage physicians to report their cases to the euthanasia review committee and to use the recommended drugs for euthanasia and thus improve quality of euthanasia performance, a strong signal is needed from the medical community, for example, through official advice from the National Belgian Disciplinary Board of Physicians. Future studies should focus on the euthanasia practice with nonrecommended drugs, physicians' motives to intentionally hasten death with nonrecommended drugs, and possible complications associated with nonrecommended euthanasia practice.

      Disclosures and Acknowledgments

      The authors thank the entire team of the Flemish Agency for Care and Health, Jef Deyaert, MSc, and Lenzo Robijn, MSc, of the End-of-Life Care Research Group of VUB & Ghent University, as well as Brecht Haex, MSc, and lawyer Wim De Brock for their contributions to the data collection. They are also deeply indebted to the thousands of Flemish physicians participating in the survey. They further thank the Belgian Medical Disciplinary Board for recommending the study and Helen White for language review of this article. This study is part of the Flanders Study to Improve End-of-Life Care and Evaluation Tools (FLIECE) project, a collaboration between the VUB, Ghent University, the Katholieke Universiteit Leuven, Belgium, and VU University Medical Center Amsterdam, The Netherlands. The study is supported by a grant from the Flemish Government Agency for Innovation by Science and Technology (Agentschap voor Innovatie door Wetenschap en Technologie) (SBO IWT nr. 100036 ). Analysis and writing were supported by the Research Council of the VUB (SRP4). The funding sources had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the article.
      Ethical approval: Ethical approval was obtained from the Ethical Review Board of the University Hospital of the VUB (reference no. 143201316288; February 8, 2013). Physicians' participation was regarded as implicit consent, which was noted in the accompanying letter introducing the study. The authors declare no conflicts of interest.

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