Palliative sedation - revised recommendations.

Palliative sedation is defined as the monitored use of medications intended to induce a state of decreased or absent awareness (unconsciousness) to relieve the burden of otherwise intractable suffering in a manner ethically acceptable to the patient, their family, and healthcare providers. In Switzerland, the prevalence of continuous deep sedation until death increased from 4.7% in 2001 to 17.5% of all deceased in 2013, depending on the research method used and on regional variations. Yet, these numbers may be overestimated due to a lack of understanding of the term "continuous deep sedation" by for example respondents of the questionnaire-based study. Inadequately trained and inexperienced healthcare professionals may incorrectly or inappropriately perform palliative sedation due to uncertainties regarding its definitions and practice. Therefore, the expert members of the Bigorio group and the authors of this manuscript believe that national recommendations should be published and made available to healthcare professionals to provide practical, terminological, and ethical guidance. The Bigorio group is the working group of the Swiss Palliative Care Society whose task is to publish clinical recommendations at a national level in Switzerland. These recommendations aim to provide guidance on the most critical questions and issues related to palliative sedation. The Swiss Society of Palliative Care (palliative.ch) mandated a writing board comprising four clinical experts (three physicians and one ethicist) and two national academic experts to revise the 2005 Bigorio guidelines. A first draft was created based on a narrative literature review, which was internally reviewed by five academic institutions (Lausanne, Geneva, Bern, Zürich, and Basel) and the heads of all working groups of the Swiss Society of Palliative Care before finalising the guidelines. The following themes are discussed regarding palliative sedation: (a) definitions and clinical aspects, (b) the decision-making process, (c) communication with patients and families, (d) patient monitoring, (e) pharmacological approaches, and (f) ethical and controversial issues. Palliative sedation must be practised with clinical and ethical accuracy and competence to avoid harm and ethically questionable use. Specialist palliative care teams should be consulted before initiating palliative sedation to avoid overlooking other potential treatment options for the patient's symptoms and suffering.

Palliative sedation: ethics in clinical practice guidelines - systematic review.

OBJECTIVES: The objective of our study was to determine whether, and to what degree, the ethical dimension was present in clinical practice guidelines (CPGs) on palliative sedation, and to identify the ethical issues with respect to the different forms of this practice. The purpose was purely to be descriptive; our aim was not to make any kind of normative judgements on these ethical issues or to develop our own ethical recommendations. METHODS: We performed a systematic review of CPGs on the palliative sedation of adults, focusing our analysis on the ethical dimension of these texts and the ethical issues of this practice. The study protocol is registered on PROSPERO. RESULTS: In total, 36 current CPGs from four continents (and 14 countries) were included in our analysis. Generally, ethics was rarely referred to or absent from the CPGs. Only six texts contained a specific section explicitly related to ethics. Ethical issues were named, conceptualised and presented in heterogeneous, often confusing ways. It was impossible to identify the ethical issues of each form of palliative sedation. Ethics expertise was not involved in the development of most of the CPGs and, if it was, this did not always correlate with the ethical dimension of the document. CONCLUSIONS: Effective cooperation between palliative care clinicians and ethicists should be encouraged, in order to integrate in particular the crucial ethical issues of continuous deep sedation until death when developing or updating CPGs on palliative sedation.

Should continuous deep sedation until death be legally regulated in Switzerland? An exploratory study with palliative care physicians.

Background: In Switzerland, continuous deep sedation until death (CDSUD) is not legally regulated and the current clinical practice guidelines on palliative sedation from 2005 do not refer to it. In contrast, in France, a neighbouring country, CDSUD is regulated by a specific law and professional guidelines. International studies show that in culturally polymorphic countries, there are variations in the end-of-life practices between linguistic regions and that a linguistic region shares many cultural characteristics with the neighbouring country. Objectives: This study aimed to explore the attitudes of palliative care physicians from the French-speaking part of Switzerland on the question of whether CDSUD should be legally regulated in the country, and to identify their arguments. Our study also aimed to assess whether a hypothetical Swiss law on CDSUD should be similar to the current legal regulation of this practice in France. Design: We conducted a multicentre exploratory qualitative study based on face-to-face interviews with palliative care physicians in the French-speaking part of Switzerland. Methods: We analysed the interview transcripts using thematic analysis, combining deductive and inductive coding. Results: Most of the participants were opposed to having specific legal regulation of CDSUD in Switzerland. Their arguments were diverse: some focused on medical and epistemological aspects of CDSUD, whereas others emphasized the legal inconvenience of having such regulation. None had the opinion that, if CDSUD were legally regulated in Switzerland, the regulation should be similar to that in France. Conclusion: This study allows to better understand why palliative care physicians in French-speaking Switzerland may be reluctant to have legal regulation of CDSUD. Further studies covering the whole country would be needed to gain a more complete picture of Swiss palliative care physicians on this question.

'How is it possible that at times we can be physicians and at times assistants in suicide?' Attitudes and experiences of palliative care physicians in respect of the current legal situation of suicide assistance in Switzerland.

INTRODUCTION: Switzerland lacks specific legal regulation of assistance in suicide. The practice has, however, developed since the 1980s as a consequence of a gap in the Swiss Criminal Code and is performed by private right-to-die organisations. Traditionally, assistance in suicide is considered contrary to the philosophy of palliative care. Nonetheless, Swiss palliative care physicians regularly receive patient requests for suicide assistance. Their attitudes towards the legal regulations of this practice and their experience in this context remain unclear. OBJECTIVES: Our study aimed to explore and describe the attitudes and experiences of Swiss palliative care physicians concerning the legal situation of suicide assistance. METHODS: In 2019, we performed an exploratory interview study with 12 Swiss palliative care physicians on palliative sedation as an alternative to assisted suicide. In this paper, we present the results that emerged from a thematic subanalysis of the data. RESULTS: Participants stated that assistance in suicide and palliative care are based on opposing philosophies, but they admitted a shift in paradigm over the last years in the sense that one practice does not necessarily exclude the other. They reported various roles in suicide assistance and considered that the current activities of Swiss right-to-die organisations were problematic and needed to be regulated by law. DISCUSSION AND CONCLUSION: These results could enrich national and international reflection on suicide assistance in the context of palliative care by reducing confusion between the two practices and strengthening the confidence of patients and their relatives.

Clinical Practice Guidelines on Palliative Sedation Around the World: A Systematic Review.

Objective: The principal aim of this study was to identify, systematically and transparently, clinical practice guidelines (CPGs) on palliative sedation from around the world. Methods: A systematic search was performed using 5 databases, grey literature search tools, citation tracking, and contact with palliative care experts across the world. Current CPGs accredited by an international, national, or regional authority, published in English, German, French, or Italian, were subjected to content analysis. Results: In total, 35 CPGs from 14 countries and 1 international CPG were included in the analysis. The CPGs had diverse formal characteristics. Their thematic scope was difficult to analyze and compare because of differences in the terms and definitions of palliative sedation in those texts. We identified 3 main situations: (1) CPGs with a fully explicit thematic scope; (2) CPGs with a partially explicit thematic scope; and (3) CPGs without an explicit thematic scope. Several CPGs explicitly stated what forms of sedation were excluded from the text. However, this presentation was often confusing. Conclusion: Our review provides several pieces of information that could guide international reflections in this field, and be used to develop or update CPGs at all levels. Efforts should be made to clarify the thematic scope of each CPG on palliative sedation, in order to generate an understanding of the forms of this therapy addressed in the text.

Ethical challenges in palliative sedation of adults: protocol for a systematic review of current clinical practice guidelines.

INTRODUCTION: This study aims to identify the full spectrum of ethical challenges of all forms of palliative sedation for adults as presented in current clinical practice guidelines (CPGs) and to determine whether CPGs specify ethical challenges of this therapy for patients with cancer and non-cancer and, if so, how exactly they do this. To the best of our knowledge, no studies have yet investigated this topic. The purpose is purely descriptive; our aim is not to make any kind of normative judgements on these challenges. Nor is our aim to assess the quality of the CPGs. METHODS AND ANALYSIS: We will perform a systematic review of CPGs on palliative sedation for adults via five electronic databases, grey literature search tools, citation tracking and contact with palliative care experts. Current CPGs accredited by an international, national or regional authority, published in English, German, French, Italian or Polish, from 2000 to the date of the search, will be subjected to content analysis at the textual, linguistic and thematic levels. ETHICS AND DISSEMINATION: This is a protocol for a systematic review and no human will be involved in this research. Therefore, ethics approval and consent to participate are not applicable to this context. This study protocol is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols criteria and registered on PROSPERO. Moreover, the integral version of this study protocol is published as a preprint on Research Square. The results of this study will be actively disseminated through peer-reviewed journals and books, international, national and local conference presentations, social media and media in general.

[Clinical ethics and uncertainty: an inseparable duo for the benefit of the patient]. / Éthique clinique et incertitude : un indissociable duo au bénéfice du patient.

Clinical ethics can be conceived as thought marked by uncertainty and on uncertainty. Its difficulties must be highlighted and discussed, in order to help guide the actions of caregivers, both on a scientific and human level, for the benefit of the patient. As an intellectual and moral virtue, humility is likely to favour a high standard of reflection and action.

A qualitative study on continuous deep sedation until death as an alternative to assisted suicide in Switzerland.

BACKGROUND: According to the European Association for Palliative Care, decisions regarding palliative sedation should not be made in response to requests for assisted dying, such as euthanasia or assisted suicide. However, several studies show that continuous deep sedation until death (CDSUD) - a particular form of sedation - has been considered as an alternative to these practices in some countries. In Switzerland, where assisted suicide is decriminalized and CDSUD is not legally regulated, no studies have comprehensively investigated their relation. Our study aimed to identify and describe the experience among palliative care physicians of CDSUD as a potential alternative to assisted suicide in the French-speaking part of Switzerland. METHODS: We performed an exploratory multicentre qualitative study based on interviews with palliative care physicians in the French-speaking part of Switzerland and conducted linguistic and thematic analysis of all interview transcripts. The study is described in accordance with COREQ guidelines. RESULTS: We included 10 interviews conducted in four palliative care units. Our linguistic analysis shows four main types of sedation, which we called 'rapid CDSUD', 'gradual CDSUD', 'temporary sedation' and 'intermittent sedation'. CDSUD (rapid or gradual) was not considered an alternative to assisted suicide, even if a single situation has been reported. In contrast, 'temporary' or 'intermittent sedation', although not medically indicated, was sometimes introduced in response to a request for assisted suicide. This was the fact when there were barriers to an assisted suicide at home (e.g., when transfer home was impossible or the patient wished not to burden the family). CONCLUSION: These preliminary results can guide clinical, ethical, linguistic and legal reflection in this field and be used to explore this question more deeply at the national and international levels in a comparative, interdisciplinary and multiprofessional approach. They can also be useful to update Swiss clinical guidelines on palliative sedation in order to include specific frameworks on various sedation protocols and sedation as an alternative to assisted suicide. Potential negative impacts of considering palliative sedation as an alternative to assisted suicide should be nuanced by open and honest societal debate.

« Sédation ¼ ou « pratiques sédatives à visée palliative en fin de vie ¼ ? Une étude linguistique des recommandations francophones en matière de sédation en soins palliatifs chez l'adulte.

Introduction : Despite the number and importance of French-language guidelines related to palliative sedation for adults, these texts have never been the subject of a linguistic analysis.Objectives : This study aimed to explore and analyze the terms used for sedation and their definitions in Belgian, French, Quebec, and Swiss guidelines.Methods : Current documents were subjected to textual, terminological, and conceptual analysis.Results : Belgian, Quebec, and Swiss guidelines use the same term to refer to sedation, without, however, conceptualizing it in a consistent way. By contrast, guidelines developed in France use various terms but define sedation in a similar (but not identical) way. Cultural specificities linked to end-of-life legislation in those countries and region were identified as a potential causal factor.Discussion and conclusion : The diversity of terms and definitions inevitably reinforces the imprecision of the medical language, and the terminology in particular. This is likely to have a negative impact on communication between healthcare professionals, patients, and their families. Efforts should be made to homogenize the terminology and definitions used in guidelines.

[Current status of clinical practice guidelines on palliative sedation for adults in French-speaking countries]. / État des lieux des recommandations sur la sédation palliative chez l'adulte dans les pays francophones.

INTRODUCTION: Many clinical practice guidelines on palliative sedation have been developed. To date, studies on French-language guidelines are lacking, despite the specific and potentially influential end-of-life positions taken by some French-speaking countries. This study aimed to perform a systematic review of the guidelines related to palliative sedation for adults in French-speaking countries, taking a synchronic and diachronic approach (current and former guidelines). METHODS: Guidelines published in French since 2000 were searched for multiple databases. In addition, prominent palliative care experts in French-speaking countries were contacted individually. A content analysis of all guidelines was conducted. RESULTS: A total of 21 guidelines from 18 countries were identified. Among them, at the time of the data collection, 14 guidelines were effectively compiled in four countries or provinces: Belgium, France, Canada (Quebec) and Switzerland. No guidelines were found for African countries. The recommendations analyzed were very heterogeneous in form (simple proposals or formal guidelines) and in substance (i.e. different types of sedation). DISCUSSION AND CONCLUSION: The quantity and volume of the guidelines found and the heterogeneity of the terminology prevented a detailed analysis of the content of the texts. An analysis must be performed using a synchronic approach only and focusing on a specific element of one type of sedation.

Nurses' experience with palliative sedation procedures in line with the 2005 Swiss guidelines: an exploratory study.

Many international studies have shown that the process of palliative sedation in an end-of-life context can be an adverse, even emotionally distressing experience for nurses. However, to the best of our knowledge, the experience of nurses working in palliative care in Switzerland has never been explored. The purpose of our study was, therefore, to understand and describe nurses' experience with the process of palliative sedation in line with the Swiss guidelines developed in 2005. We opted for an exploratory qualitative monocentric study using comprehensive individual interviews to achieve this objective. A total of 10 nurses were approached, and nine agreed to take part. After the interviews were transcribed, eight were ultimately included in the analysis. This analysis shows that nurses' attitudes toward the process of palliative sedation tended to be hesitant, resistant, or confident and that this was linked to the length of time they had worked in palliative care. These findings suggest that the 2005 Swiss guidelines do not protect nurses against the uncertainty related to process of palliative sedation. A national comprehensive multicentric study therefore needs to be developed to consolidate these results.

[Conceptualization of palliative sedation by nurses working in a palliative care unit in French-speaking Switzerland: An exploratory qualitative study]. / La conceptualisation de la sédation palliative par des infirmiers exerçant au sein d'une unité de soins palliatifs en Suisse romande. Une recherche qualitative exploratoire.

Introduction : The concept of palliative sedation is not defined in a uniform way at the international level. In Switzerland, it is outlined by the recommendations issued in 2005.Background : The conceptualization of palliative sedation by nurses is likely to be heterogeneous, due to the diversity of local protocols but also to personal experiences. This poses both epistemological and practical difficulties. Although this point is crucial to take into account in order to define the object of future studies in Switzerland, it has not yet been explored in the French-speaking part of Switzerland.Objectives : To discover and describe the conceptualization of palliative sedation by nurses in a palliative care unit in French-speaking Switzerland.Methods : Exploratory qualitative research with comprehensive individual interviews.Results : Palliative sedation is considered as a treatment of last resort for one or more refractory symptoms. The search for the lowest effective dose and the temporary (at least initially) character of sedation are the main elements put forward by nurses.Discussion and conclusion : The conceptualization of palliative sedation is consistent withSwiss recommendations. These results form a basis for developing a national study on the subject.

Imaging analyses of coagulation-dependent initiation of fibrinolysis on activated platelets and its modification by thrombin-activatable fibrinolysis inhibitor.

Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the centre of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy. The structure of the fibrin network formed by supplemented tissue factor was uneven and denser at the sites of coagulation initiation regions (CIRs) on PS-exposed platelets. When tissue-type plasminogen activator (tPA; 7.5 nM) was supplemented, labelled plg (50 nM) as well as tPA accumulated at CIRs, from where fibrinolysis started and gradually expanded to the peripheries. The lysis time at CIRs and their peripheries (50 µm from the CIR) were 27.9 ± 6.6 and 44.4 ± 9.7 minutes (mean ± SD, n=50 from five independent experiments) after the addition of tissue factor, respectively. Recombinant human soluble thrombomodulin (TMα; 2.0 nM) attenuated the CIR-dependent plg accumulation and strongly delayed fibrinolysis at CIRs. A carboxypeptidase inhibitor dose-dependently enhanced the CIR-dependent fibrinolysis initiation, and at 20 µM it completely abrogated the TMα-induced delay of fibrinolysis. Our findings are the first to directly present crosstalk between coagulation and fibrinolysis, which takes place on activated platelets' surface and is further controlled by thrombin-activatable fibrinolysis inhibitor (TAFI).

Activities of wild-type and variant tissue-type plasminogen activators retained on vascular endothelial cells.

We reported that tissue-type plasminogen activator (tPA) secreted from vascular endothelial cells (VECs) is retained on the cell surface and effectively evokes both plasminogen activation and fibrin clot dissolution (fibrinolysis) on VECs. Here, to evaluate possibly different behaviors of variants of tPA, we quantitatively assessed these two events separately using green fluorescent protein (GFP)-conjugated tPA in cultured human VECs. The amount of secreted wild-type tPA-GFP correlated well with both the activities of plasminogen activation (r = 0.66) and fibrinolysis (r = -0.93). A variant of tPA-GFP, with a lower affinity to the surface of VECs but higher affinity to fibrin, showed higher fibrinolysis and lower plasminogen activation activity compared to the wild-type.

Bidirectional functions of thrombin on fibrinolysis: Evidence of thrombin-dependent enhancement of fibrinolysis provided by spontaneous plasma clot lysis.

Besides procoagulant activity, thrombin exhibits anticoagulant and profibrinolytic activities. We demonstrated that the euglobulin clot lysis time (ECLT) was shortened by endogenously generated thrombin as a result of the inactivation of plasminogen activator inhibitor type 1 (PAI-1). In contrast, thrombin suppressed fibrinolytic activity through the activation of thrombin activatable fibrinolysis inhibitor (TAFI). Here, using three different clot lysis assays of the ECLT, the tissue plasminogen activator supplemented plasma clot lysis time (tPA-PCLT) and the spontaneous plasma clot lysis time (s-PCLT), we analyzed how the coagulation process modifies fibrinolysis. The ECLT was shortened by exogenously supplemented thrombin in a dose-dependent manner in the absence of calcium ion (Ca(++)), whereas this shortening was not observed in the presence of Ca(++) where endogenous prothrombin was effectively activated to thrombin. This shortening was also not observed for the tPA-PCLT, in which tPA is supplemented in excess and PAI-1 activity is mostly lost. On the contrary, thrombin dose-dependently prolonged the tPA-PCLT, which was mostly abolished by inhibitors of carboxypeptidase and activated FXIII, suggesting that the prolongation is TAFI- and Factor XIII-dependent. The s-PCLT was shortened when thrombin generation was boosted by supplementing tissue factor and phosphatidylserine together with Ca(++), which was more apparent in the presence of inhibitors of activated FXIII and activated TAFI. Thus, thrombin appeared to express its enhancing effect on fibrinolysis even in plasma, in addition to its inhibiting effect. These bidirectional functions of thrombin on fibrinolysis seem to take place on demand under different environments to maintain adequate vascular blood flow.

[Analysis of notifications of suspicions of diseases caused by the way the job is performed in the context of pathologies regarded as occupational diseases]. / Analiza zgloszei podejrzenia chorób wywolanych sposobem wykonywania pracy w kontekscie patologii uznanych za choroby zawodowe.

BACKGROUND: In this report the increase in the number of notifications of suspicions of diseases caused by the way the job is per formed, observed recently in the Regional Center of Occupational Medicine in Wroclaw, is highlighted. The problem stems from the recognition of medical certification of such diseases as occupational diseases only in one third of all notifications of suspicions. MATERIAL AND METHODS: The case study was based on statistical data concerning notifications of suspected occupational diseases collected in the Branches of the Regional Center of Occupational Medicine in Wroclaw in the years 2006-2011, as well as on medical certificates issued by the Center's Out-patient Clinics of Occupational Diseases. More than 700 reports of suspected chronic occupational diseases of the musculoskeletal system and chronic diseases of the peripheral nervous system caused by the way the job is performed were analyzed, taking into account gender, age and how the work had been done. On the basis of the analysis of medical certificates issued by physicians, decision-making procedures and the recognition of occupational disease certification are discussed. RESULTS: The analysis of the data collected in the Regional Center of Occupational Medicine, Wroclaw, in the years 2006-2011 showed a significant increase in the percentage of notifications of suspicions of diseases caused by the way the job is performed. At the same time it was shown that only about one third of reported suspicions were concluded with issuing medical certification of an occupational disease and the administrative confirmation of the decision. CONCLUSIONS: The results of the study revealed significant certification problems in the group of diseases caused by the way the job is performed in terms of the recognition of this type of pathology as an occupational disease. These issues are ambiguous because of a large number of non-occupational factors involved in the pathogenesis of these diseases.