From Sedation to Continuous Sedation Until Death: How Has the Conceptual Basis of Sedation in End-of-Life Care Changed Over Time?

Transcription

1 Vol. 46 No. 5 November 2013 Journal of Pain and Symptom Management 691 Review Article From Sedation to Continuous Sedation Until Death: How Has the Conceptual Basis of Sedation in End-of-Life Care Changed Over Time? Evangelia S. Papavasiliou, MRes, Sarah G. Brearley, PhD, Jane E. Seymour, PhD, Jayne Brown, PhD, and Sheila A. Payne, PhD, on behalf of EURO IMPACT International Observatory on End of Life Care (E.S.P., S.G.B., S.A.P.), Lancaster University, Lancaster; Sue Ryder Centre for the Study of Supportive, Palliative and End of Life Care (J.E.S.), University of Nottingham, Nottingham; and Centre for the Promotion of Excellence in Palliative Care (J.B.), De Montfort University, Leicester, United Kingdom Abstract Context. Numerous attempts have been made to describe and define sedation in end-of-life care over time. However, confusion and inconsistency in the use of terms and definitions persevere in the literature, making interpretation, comparison, and extrapolation of many studies and case analyses problematic. Objectives. This evidence review aims to address and account for the conceptual debate over the terminology and definitions ascribed to sedation at the end of life over time. Methods. Six electronic databases (MEDLINE, PubMed, Embase, AMED, CINAHL, and PsycINFO) and two high-impact journals (New England Journal of Medicine and the British Medical Journal ) were searched for indexed materials published between 1945 and This search resulted in bibliographic data of 328 published outputs. Terms and definitions were manually scanned, coded, and linguistically analyzed by means of term description criteria and discourse analysis. Results. The review shows that terminology has evolved from simple to complex terms with definitions varying in length, comprising different aspects of sedation such as indications for use, pharmacology, patient symptomatology, target population, time of initiation, and ethical considerations, in combinations of a minimum of two or more of these aspects. Conclusion. There is a pressing need to resolve the conceptual confusion that currently exists in the literature to bring clarity to the dialogue and build a base of commonality on which to design research and enhance the practice of sedation in end-of-life care. J Pain Symptom Manage 2013;46:691e706. Ó 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Address correspondence to: Evangelia S. Papavasiliou, MRes, International Observatory on End-of-Life Care, Furness (C85), Lancaster University, Lancaster Ó 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. LA1 4YT, United Kingdom. e.papavasiliou@ lancaster.ac.uk Accepted for publication: December 7, /$ - see front matter

2 692 Papavasiliou et al. Vol. 46 No. 5 November 2013 Key Words Sedation, end of life, terminology, definitions, conceptual debate, palliative care, evidence review Introduction Sedation in palliative care is a complex medical and ethical topic. Despite a number of prospective studies 1e6 and published guidelines, 7e11 evidence on which to base practice and research on sedation has remained limited, and controversial issues persist about almost every aspect of the practice. 12 Perhaps the most challenging aspect concerns matters of terminology and meanings assigned to sedation. 13 This evidence review seeks to explore changes in terms and definitions ascribed to the practice over time, the main focus being on sedation in end-of-life care, which, for the purpose of this article, should be understood as comprehensive care for dying patients in the last few hours or days of life. 14 There have been numerous attempts to define sedation without consensus among experts. The challenges in achieving such consensus may account for the lack of conceptual clarity. 15 The fact that palliative care experts have struggled with finding an agreed term for the practice should be taken as a sign that this is an area of research filled with complexity. 16 Various terms have been suggested and been used to describe sedation. 3,17e22 Which of these terms best describes the practice is still under question. 23 Terms may have different meanings, but are often used as synonyms, 24 some of which can have varying connotations and implications for normal practice. 25 As a consequence, there is uncertainty regarding the interpretation of even simple data, such as the prevalence of sedation, 26 creating confusion in both clinical and research fields. 27e29 Lack of a clear definition and conceptualization of sedation is a major contributor to this uncertainty. Such heterogeneity in proposed definitions, based on the lack of a universally accepted term, indicated the need to integrate the many existing definitions of the practice with a more detailed description. 7,19,20,30e32 Still, confusion and inconsistency in the literature related to the conceptual basis of sedation persevere, making interpretation, comparison, and extrapolation of many studies and case analyses problematic. 33 The present review aims to address this conceptual debate over the terminology and definitions of sedation, providing an overview and analysis of names and meanings ascribed to the practice over time and making suggestions for clarifying some of the associated problems. This is the first historical review to take account of the longest temporal distribution of published outputs in the existing literature, comprising articles published between 1945 and Data Sources A review of articles published between June 1945 (the end of World War II in Europe, which marked advances in modern medical techniques and the emergence of bioethics) and October 2011 addressing the changes in names and definitions ascribed to sedation was conducted. The main focus was placed on sedation prescribed continuously to induce a total loss of consciousness until death occurs (i.e., continuous sedation until death) because this form of sedation has generated much discussion about conditions and modalities of its use as well as associations between sedation and euthanasia, giving rise to huge controversy at both a clinical and bioethical level. Published outputs were identified from six electronic databases, namely MEDLINE, PubMed, Embase, PsychINFO, AMED, and CI- NAHL. The British Medical Journal and the New England Journal of Medicine were manually searched. Reference lists from past reviews also were hand searched and key aricles were added to data sources. Search words included combinations of terms developed using the thesaurus of Medical Subject Headings and key words that occurred at least twice during the manual scanning of existing reviews. Criteria relating to the objectives of the article, such as participant criteria, outcome

3 Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 693 measures, language, and time frame, were established and used to guide the literature search. More specifically, inclusion criteria comprised published outputs (i.e., empirical research articles, conceptual theoretical articles, letters, editorials, reviews, brief reports, comments, legal cases, case reports, news, and patients handouts) focusing on adult patients suffering from advanced incurable disease, actively dying, with death expected in hours or days (participant criteria). Published outputs examining intermittent, mild/moderate, or conscious sedation were excluded (outcome measures). Only articles written in English (language) and published in peerreviewed journals between January 1945 and October 2011 (time frame) were included. Assessment of the 9255 published outputs retrieved in the first search, on the basis of the described data extraction procedure, left 328 articles that fulfilled all criteria, and these were further analyzed. Describing Sedation in End-of-Life Care Terms to describe sedation were manually recorded in chronological order of first occurrence and coded based on linguistic criteria of term description. Initial classification included two broad categories, namely simple terms (i.e., one-word or compound terms) vs. complex terms (i.e., terms comprising two or more words). The latter was further scrutinized to include groupings such as two-word and three-word terms (i.e., terms including a range of adjectives attached to sedation ), descriptive terms (i.e., terms documenting conceptual change that could not be expressed in three words or less), classification terms (i.e., terms based on the degree and duration of sedation), and classification of further descriptive terms (i.e., terms that combined elements of both classification and descriptive groupings). Table 1 summarizes term classification over time. The Challenge of Terminology In a 1963 retrospective study, Neder et al. 34 examined the role of sedation (the first term identified to describe the practice) on survival rate in status asthmaticus, focusing on the effects sedative medication had on patients diagnosed with a severe case of asthma 36 hours before their death. 34 Followed by a gap in the literature, scientific research and publications on sedation resumed in the early 1990s. 35 In a 1990 prospective study, Ventafridda et al. 1 attempted to document the time between physical symptom occurrence and death in a group of patients with cancer. Such symptoms were assessed as unendurable to patients and controllable only by sedation-inducing sleep. Thus, the practice was referred to as sedation-induced sleep. 1 It might have been this shift in target population, with studies focusing on sedation in terminally ill patients, more specifically patients suffering terminal cancer, which gave rise to the term terminal sedation. In a 1991 review, Enck 17 was the first to introduce this term, which appeared to be the most controversial term ever used to describe the practice. Its appropriateness was heavily criticized as bearing obvious negative connotations, implying that the intent behind sedation is death instead of a means to control difficult symptoms, drawing associations with euthanasia. 16,36,37 Based on such associations, Billings and Block 18 referred to the practice as slow euthanasia, suggesting that inducing sedation in terminally ill patients will assuredly lead to a comfortable death, but not too quickly. To promote ethical correctness and avoid misperception in the public eye, both terms fell out of favor, the latter never being encountered in the literature again. The next alternative was total pharmacological sedation or its shorter version total sedation, suggesting the use of sedative medication either to obtain total loss of consciousness or total relief of suffering, respectively. 3,36 To refine controversies raised over the morality of the practice and also unify pre-existing terms, palliative emerged as the new adjective to describe sedation. 37 This term was regarded as less charged, linguistically precise, and clinically accurate. 16,38 Unlike other terms, it was used to denote what the practice was all about, that is, palliation. 39 Its etymology implied sheltering a patient from distress, via inducing a state of restfulness. 38 Moreover, this term would induce less conflict and thus be more desirable for health care providers who were seen to underprescribe in the

4 Year Simple (One Word/ Compound) Table 1 Terms Used to Describe Sedation Over Time (First Occurrence Recorded) Complex Two Words Three Words Descriptive Classification (Based on Degree and Duration) Progressive sedation Sedation Sedation-induced sleep Terminal sedation 17 Heavy sedation/continuous somnolence High-dose analgesia to induce sleep 60 Deep sedation Sedation in the management of refractory symptoms Slow euthanasia Sedation for intractable distress in the dying Total pharmacological sedation Palliative sedation 27 Sedation in the imminently dying 28 Sedation for intractable distress of a dying patient Total sedation 36 Sedation therapy 84 Palliative sedation therapy Sedation for comfort at the end of life 31 Continuous deep sedation 42 Sedation for palliation of terminal symptoms Sedation in the terminal or final stages of life Controlled sedation 22 Sedation in the agony Palliative sedation to unconsciousness Early terminal sedation 85 Palliative sedation until death 87 End-stage palliative sedation Controlled sedation for refractory symptoms in dying patients 88 Primary deep continuous sedation 41 Deep palliative sedation 45 Sedation in the last phase of life 51 Sedation at the end of life Continuous deep sedation until death Sedation in palliative medicine 52 Continuous sedation until death 46 Classification þ Descriptive Sedation to unconsciousness in dying patients 55 Continuous deep palliative sedation at the end of life Papavasiliou et al. Vol. 46 No. 5 November 2013

5 Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 695 treatment of intractable suffering, being understandably fearful of judicial interpretation. 40 However, this term was arguably the new euphemism to avoid the more distressing terminal sedation, obscuring patient autonomy, bearing similarities with physicianassisted death and confusing sedation with palliative care. 41 Because palliative care covers a wide spectrum of physical states, only one of which is end of life, palliative sedation was not perceived to communicate the actual context of the practice. 16 Morita et al. 21 extended palliative sedation to palliative sedation therapy, suggesting that the practice should be further classified into subgroups according to its degree and duration. Based on this suggestion, a series of classification terms emerged (continuous deep sedation, 42 palliative sedation to unconsciousness, 43 primary deep continuous sedation, 41 continuous deep sedation until death, 44 deep palliative sedation, 45 and continuous sedation until death 46 ). Our findings show that the classification terms pre-existed in the literature (heavy sedation, 47 progressive sedation, 48 and deep sedation 49 ), although these terms were used as synonyms for terminal sedation in studies conducted to assess sedation prescribed for terminally ill patients with cancer. This classification seemed logical and practical. However, the variability observed in classifying and defining different forms of sedation posed major challenges regarding the application of the practice in patients who were terminally ill, having reached the final stages of dying. 44 Descriptive terminology was introduced early in the literature mainly to counteract issues of ethical acceptability of the practice. To prevent potential confusion or misunderstanding and restrict space for open interpretation, descriptive terms for sedation were developed. Such terms prevailed, especially after terminal sedation and the associations drawn between sedation and euthanasia implying that sedation is in fact a terminal event. 50 A series of descriptive terms emerged focusing on specific aspects of sedation, such as indications for use (i.e., sedation in the management of refractory symptoms 7 and sedation for palliation of terminal symptoms 16 ), target population (i.e., sedation in the imminently dying 28 ), time of initiation (i.e., sedation in the last phase of life 51 or sedation in the final stages of life 32 ), and setting (i.e., sedation in palliative medicine 52 ). In some instances, combinations of such aspects were incorporated in the same term (i.e., sedation for intractable distress in the dying 19 [indications and target population] and sedation for comfort at the end of life 31 [indications and time of initiation]). Although the rationale to account for the choice of each descriptive term was clearly explained, these terms were often too cumbersome to become part of medical jargon and thus unable to draw universal acceptance. 16,38 In addition, the use of phrases such as terminally ill, terminal symptoms, refractory symptoms, imminently dying, and actively dying were all open to interpretation that could cause confusion, especially to those outside of palliative medicine. 53 Descriptive terms could also fail to become standardized when they include aspects that are culturally driven. For instance, Gonzalez Baron et al. 54 named the practice sedation in the agony, a concept considered more suitable for the chronological moment, with agony referring to the state that precedes death in those illnesses in which life gradually extinguishes. 54 This culturally driven concept, not easily understood outside the country from which it originated, could be the reason that prevented this term from becoming universally accepted. On classification, further descriptive terms emerged via combining classification terms and aspects of descriptive terms. Curlin et al. 55 and Juth et al. 56 were found to use such terms, the former in a survey questionnaire and the latter in an ethical discussion of the European Association for Palliative Care Framework. However, they failed to provide any further explanation for such a choice of term. Interestingly, the three most dominant terms recorded to describe sedation were terminal sedation, palliative sedation, and sedation. Terminal sedation, despite being heavily criticized, persevered in the literature probably because, once used, the concept of terminal was associated with the patient s situation, that is, terminal cancer, not the objective of the treatment. Palliative sedation might have persisted as the alternative to terminal sedation to avoid misperception and eliminate

6 696 Papavasiliou et al. Vol. 46 No. 5 November 2013 the danger of associating terminal with the intention to terminate life by hastening death. Literature confirms these terms as being the most preferred terms used to describe the practice over time. 57 And finally, sedation, the first simple term identified, recurred, probably signifying that, although various adjectives and descriptive words have been used to describe the practice and changed over time, the actual concept of sedation has not changed. A number of experts refer to it as sedation, without having to add any more words to the term and still appear to talk about the same practice. Defining Sedation in End-of-Life Care Similarly, definitions of sedation were manually recorded in chronological order of original contributions in the literature in association with the term they were used to define. These definitions were linguistically analyzed into the aspects of sedation they comprised by means of discourse analysis (i.e., highlighting the social categories that already exist within the text and the assumptions, meanings and values that lie behind the text constructed through the language used, the end point being not to seek answers but seek the meanings that contribute to a particular view 58,59 ). Definitions that cited, paraphrased, or referred to pre-existing ones were not recorded. Table 2 summarizes definitions (original contributions) ascribed to sedation over time. The Semantics of Definitions The first definition was identified in 1994, more than 30 years after the first term (i.e., sedation) occurred, being part of the first guidelines published on sedation when the term proposed was sedation in the management of refractory symptoms. 7 The focus was not on defining the practice itself but rather on defining the symptoms for which the practice should be prescribed. A series of terms were seen to pre-exist in the literature but no attempt was made at definition. 1,17,34,47e49,60 The first attempt to define sedation as a practice was recorded in 1996 when Billings and Block 18 suggested that it should be called slow euthanasia. Associating sedation with euthanasia placed the ethical acceptability of the practice under question and generated debate in scientific circles over misperceptions and misbeliefs surrounding the concept of sedation. 23,61e66 Experts became alert to the fact that they should account for their choice of term and be specific when trying to define its concept. Thus, most articles that followed attempted to provide a clear definition of the term they used. 3,19,46,67,68 Different aspects of the practice were incorporated in definitions, such as indications for use, pharmacology, target population, patient symptomatology, time of initiation, and/or ethical considerations. Because there is no clear-cut outline of how a definition should be structured and what kind of information it should include, definitions recorded were found to vary in length depending on the information that the author(s) chose to include. 66 Our findings reveal that, although indications for use was the essential component common to all definitions, confusion and inconsistency persevere in all aspects discussed because of the lack of common language. 26 For instance, when referring to pharmacological approaches to sedation, such lack of common language was evident, with some definitions being more selective and others more explanatory with regard to the amount of details they provided (i.e., psychotropic agents, 69 in the main benzodiazepines and neuroleptics; 70 ongoing administration of barbiturates; 71 high doses of sedatives; 72 nonopioid drugs; 67 sedative medications; 21 continuous administration of sedatives or opioids; 42 by pharmacological means; 73 continuous benzodiazepines, barbiturates, or other medications; 74 monitored use of medications; 11 and the use of specific sedatives 75 ). The same applies to all aspects discussed in definitions over time. Disparity in definitions also may be attributed to a series of other factors that have to do with study centers, scientific disciplines, and authors backgrounds. More specifically, the large variability in the use of terms among study centers suggests a lack of appropriate criteria adopted for providing a clear definition that could gain universal acceptance. 76 In addition, articles came from a wide range of scientific disciplines (i.e., medicine, nursing,

7 Table 2 Definitions of Sedation Over Time (Original Contributions) Year Term Used Term Defined as Aspects Included in Definition 1994 Sedation in the management of refractory symptoms When a symptom cannot be adequately controlled despite aggressive efforts to identify a tolerable therapy that does not compromise consciousness Slow euthanasia The clinical practice of treating a terminally ill patient in a fashion that will assuredly lead to a comfortable death, but not too quickly Sedation Sedation may be defined as the prescription of psychotropic agents, in the main benzodiazepines and neuroleptics, with a view to controlling physical symptoms (pain or dyspnea), psychological symptoms (insomnia, anxiety crises, and agitation), or to make a patient unconscious in certain dramatic situations (e.g., sudden hemorrhage) Sedation A medical procedure to palliate patients symptoms by intentionally making their consciousness unclear. It included an increase in morphine dose resulting in secondary somnolence and the use of sedative drugs Terminal sedation Suffering patient is sedated to unconsciousness, usually through ongoing administration of barbiturates Sedation The prescription of sedative drugs where reducing the level of consciousness was part of a treatment strategy with the aim of relieving distress Terminal sedation The intention of deliberately inducing and maintaining deep sleep, but not deliberately causing death in very specific circumstances. These are: 1) for the relief of one or more intractable symptoms when all other possible interventions have failed and the patient is perceived to be close to death, or 2) for the relief of profound anguish (possibly spiritual) that is not amenable to spiritual, psychological, or other interventions, and the patient is perceived to be close to death Sedation The prescription of psychotropic agents to control physical and psychological symptoms by making the patient unconscious Terminal sedation Is the induction and maintenance of a sedated state with the intent of relieving otherwise intractable distress, both physical and mental, in a patient close to death Sedation A medical procedure to palliate patients symptoms refractory to standard treatment by intentionally clouding their consciousness. Classification of sedation is defined as primarysecondary, intermittent-continuous, and mild-deep subcategories 93 Definition for refractory symptoms 1999 Total pharmacological sedation The administration of drugs to obtain total loss of consciousness Terminal sedation The use of high doses of sedatives to relieve extremes of physical distress Sedation for intractable distress of a dying patient (SIDD Pat) Use of sedating medications to relieve severe symptoms that cannot be controlled adequately despite aggressive efforts without sedation 20 (Continued) Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 697

8 Table 2 Continued Year Term Used Term Defined as Aspects Included in Definition 2000 Terminal sedation Is the intentional, continuous sedation of an end-stage patient for the purpose of relieving physical symptoms Terminal sedation Use of high doses of sedatives to relieve extremes of physical distress and when applied to patients who have no substantial prospect of recovery, terminal sedation refers to a similar lastresort clinical response to extreme unrelieved physical suffering Terminal sedation Heavy sedation to escape pain, shortness of breath, and other severe symptoms. The patient is sedated to unconsciousness to relieve severe physical suffering and is then allowed to die of dehydration or some other intervening complication Terminal sedation A procedure where through heavy sedation a terminally ill patient is put into a state of coma, where the intention of the doctor is that the patient should stay comatose until he or she is dead Terminal sedation The use of nonopioid drug to control refractory symptoms in the dying Terminal sedation/palliative sedation (PS) The administration of medication to relieve pain and sedate a patient, with the recognition that such medication may hasten death Terminal sedation The process by which severely suffering patients are placed under anesthesia, all supportive therapy is stopped, and they are kept in this condition until death ensues Palliative sedation therapy (PST) Use of sedative medications to relieve intractable and refractory distress by reduction in patients consciousness Proposed subcategories of PST for degree of sedation, duration, and pharmacological properties of medications; sedation was classified as mild to deep, intermittent to continuous, and primary to secondary PS The administration of sufficient doses of sedatives (typically benzodiazepines or barbiturates) to induce a continuous state of sleep Terminal sedation A procedure used to relieve patients of symptoms refractory to usual treatment by decreasing the level of consciousness in a patient close to death PS Chemically induced sedation, without intending to cause death, using a nonopioid drug to control acute or refractory symptoms that have not responded to conventional symptom management or have a severity and/or trajectory of illness that requires prompt intervention to relieve distress in patients (death expected in hours or days) with advanced and incurable disease Papavasiliou et al. Vol. 46 No. 5 November 2013

9 2002 Terminal sedation/sedation for the imminently dying Two definitions provided: Sedation as sedation of the imminently dying/a practice in which 1) the patient is close to death (hours, days, or at most a few weeks); 2) the patient has one or more severe symptoms that are refractory to standard palliative care; 3) the patient s physician vigorously treats these symptoms with therapy known to be efficacious; 4) this therapy has a dose-dependent side effect of sedation that is a foreseen but unintended consequence of trying to relieve the patient s symptoms; and 5) this therapy may be coupled with the withholding or withdrawing of life-sustaining treatments that are ineffective or disproportionately burdensome Terminal sedation/sedation toward death a practice in which 1) the patient need not to be imminently dying, 2) the symptoms believed to be refractory to treatment are simply the consciousness that one is not yet dead, 3) the patient s physician selects therapy intended to render the patient unconscious as a means of treating symptoms, and 4) other life-sustaining treatments are withdrawn to hasten death Continuous deep sedation As continuous administration of sedatives or opioids to the point where the patient almost or completely loses consciousness, with the primary aim that the patient does not experience suffering Sedation The reduction of the level of consciousness of the patient to alleviate intolerable symptoms and distress Terminal sedation The administration of sedative drugs with the aim to reduce consciousness of a terminal patient to relieve distress; it is frequently accompanied by the withdrawal (or withholding) of life-sustaining interventions, such as hydration and nutrition Sedation in the terminal or final stages The use of sedative drugs (usually benzodiazepines with or without complementary opioids given by the subcontinuous route) to reduce the level of consciousness sufficiently deep to provide comfort for the patient until death occurs Terminal sedation/ps Sedating patients to unconsciousness to relieve one or more symptoms that are intractable and unrelieved despite aggressive symptom-specific treatments, and maintaining this condition until the patient dies Terminal sedation Diminishing consciousness to halt the experience of pain if a terminally ill patient has intractable pain despite aggressive analgesia Terminal sedation The administration of drugs to keep the patient in deep sedation or coma until death, without giving artificial nutrition or hydration PS The primary intention of deliberately inducing a temporary or permanent light-to-deep sleep, but not deliberately causing death, in patients with a terminal illness and specific refractory symptoms PS An intentional reduction of the vigilance by pharmacological means up to the point of complete loss of consciousness with the aim of reducing or abolishing the perception of a symptom that would otherwise be intolerable for the patient despite the implementation of the most adequate means aimed at controlling the symptom itself, which is therefore to be considered refractory PS The use of sedative medications to relieve extreme suffering by making the patient unaware and unconscious (as in deep sleep) while the disease take its course, eventually leading to death 102 (Continued) Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 699

10 Table 2 Continued Year Term Used Term Defined as Aspects Included in Definition 2005 Sedation in the agony Deliberate administration of drugs to achieve unattainable relief by other means for physical or psychological suffering, through reducing consciousness level in a patient whose death is supposed to be very close, and with explicit, implicit or delegate patient informed consent PS The use of medication to induce sedation to relieve an imminently dying patient s severe distress that cannot be controlled despite other aggressive measures PS The use of around-the-clock nonopioid medications to induce sedation in patients who at the time of initiating PS 1) were terminally ill from advanced and incurable illness, 2) had a life expectancy of days or less as judged by vital signs, urine output, and level of consciousness, 3) had intolerable acute or refractory symptoms that were not controlled by aggressive conventional management, and 4) received sedating medications without the intent of causing death PS The administration of nonopioid drugs to sedate a terminally ill patient to unconsciousness as an intervention of last resort to treat severe, refractory pain or other clinical symptoms that have not been relieved by aggressive, symptom-specific palliation PS Inducing a terminally ill palliative patient s full consciousness through intermittent or continuous application of medication at the patient s request because there was no other way to gain control over one or more refractory symptoms PST The use of sedative medications to relieve intolerable suffering by a reduction in patients consciousness PS The use of continuous intravenous benzodiazepines, barbiturates, or other medications to bring an imminently dying patient into a state of unresponsiveness to alleviate suffering from symptoms that cannot be controlled with conventional therapies 74 Patient symptomatology 2007 PS The intentional lowering of consciousness of a patient in the last phase of his or her life Sedation The monitored use of medications intended to induce varying degrees of unconsciousness to induce a state of decreased or absent awareness (unconsciousness) to relieve the burden of otherwise intractable suffering. The intention is to provide adequate relief of distress End-stage PS The continuous reduction of a patient s consciousness by use of drugs when death is imminent Papavasiliou et al. Vol. 46 No. 5 November 2013

11 2009 PS 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 that is ethically acceptable to the patient, family, and health care providers PS The intentional induction of loss of consciousness for the purpose of symptom relief PS The use of medications to reduce consciousness for the relief of intolerable and refractory symptoms, in patients with limited life expectancy PS The use of specific sedatives to relieve intolerable suffering from refractory symptoms by reducing a patient s level of consciousness PS The lowering of patient consciousness using medications for the express purpose of limiting patient awareness of suffering that is intractable and intolerable PS The use of medications to induce decreased or absent awareness to relieve otherwise intractable suffering at the end of life PS The intentional administration of sedative drugs and combinations required to reduce the consciousness of a terminal patient as much as necessary to adequately relieve one or more refractory symptoms 62 Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 701

12 702 Papavasiliou et al. Vol. 46 No. 5 November 2013 palliative care, law, and ethics), which means that different perspectives may be highlighted, and, given the authors background, definitions may be approached from different angles, drawing more attention to specific aspects. Surprisingly, the more detailed definitions (which include all aspects of the practice discussed) came from one empirical research article and one review rather than guidelines on sedation, as one might expect. 77,78 However, examining definitions produced as part of guidelines, there was an evident tendency to include more aspects over the years. Cherny and Portenoy, 7 in the first guidelines ever published on sedation, focused on patient symptomatology to define refractory symptoms; in the most recent published framework offering procedural guidelines, Cherny and Radbruch 11 also included clinical indications for sedation use, pharmacology, and ethical considerations. The latter was observed to display a tendency of receiving wider acceptance, a claim that seems to be confirmed by the literature. 57 Still, this definition has failed to account for target population and time of initiation, the aspects of sedation that should be clarified when defining the practice. Moreover, patient symptomatology is referred to as intractable suffering without being explicit enough on what suffering involves (i.e., physical suffering, existential suffering, or both). Following the same pattern, some of the definitions proposed over time either failed to include essential aspects of sedation or were not quite explicit with regard to the aspects of the practice they included. 3,9,20,61,79e81 Such definitions need further defining, especially when the aspiration/intent behind the definition is to gain universal acceptance. Literature suggests that confusion and inconsistency in definitions over time may be attributed to the lack of a universally accepted term. 26 However, our findings show that disparity persisted even when there was an attempt to define the same term. For example, terminal sedation, the most dominant term identified, was found to have multiple definitions over time, none of which has gained universal acceptance. This suggests that it might be the lack of common language, with experts in palliative care being unable to reach a consensus on the language to use to produce a single definition, rather than the absence of a standardized term that makes variation in definitions over time so dominant. Moreover, following the practice being placed under ethical scrutiny, with associations being drawn between sedation and euthanasia or physician-assisted suicide, some definitions evolved a defensive element in addition to being simply descriptive. 11,19,33,54,78,82 Attempts were made to define the practice in such a way as to highlight what the concept of sedation should not include next to what it actually did (e.g., deliberately inducing and maintaining deep sleep, but not deliberately causing death; 19 this therapy has a dose-dependent side effect of sedation that is a foreseen but unintended consequence of trying to relieve the patient s symptoms 82 ). Special emphasis was placed on ethical considerations to prevent misinterpretations that would make sedation appear morally unacceptable. Limitations This review article is subject to a series of limitations that should be addressed and accounted for in further research. The electronic search was limited to six databases, and manual searching included only two high impact journals, not all of which dated back to 1945, which was set as the starting point for this study. English was a priori set as a limit to our search. This could be a confounding factor considering that terms and definitions given in other languages were not included. The analysis did not include any outputs published in the gray literature. Outputs examining intermittent, mild/moderate, or conscious sedation also were excluded. Conclusion Given the diversity in the terms used to describe sedation and the range of understandings associated with the meaning of the practice, reaching consensus is bound to be difficult. 13 There is a pressing need to resolve the conceptual confusion that currently exists in the literature. The use of common language is essential to improve quality and achieve comparability across cases and between studies that investigate the practice of sedation. 83 To

13 Vol. 46 No. 5 November 2013 Sedation in End-of-Life Care: The Conceptual Debate 703 this end, attempts should be made to bring clarity to the dialogue and build a base of commonality on which to design research and enhance practice. The question to be raised, however, is whether there is more than a hermeneutic problem with the multiplicity of terms and definitions that suggest a fuzzy, unfocused construct actually describing a fuzzy, unfocused practice, that is, whether the inconsistent use of terms and definitions in the literature of sedation in end-of-life care reflects inconsistency and confusion underpinning its clinical practice. This issue will be addressed and accounted for in a forthcoming interview-based study with experts in the field of sedation in end-of-life care. The purpose of this article was to present a historical evidence review to record changes in terms and definitions ascribed to sedation over time. The analysis has provided a fair representation of the general trends regarding the evidence as well as a baseline with which to compare future studies. Disclosures and Acknowledgments This article is part of the European Intersectorial and Multidisciplinary Palliative Care Research Training (EURO IMPACT) project. EURO IMPACT is funded by the European Union Seventh Framework Programme (FP7/ , under grant agreement no ). EURO IMPACT aims to develop a multidisciplinary, multiprofessional, and intersectorial educational and research training framework for palliative care research in Europe. EURO IMPACT is coordinated by Professor Luc Deliens and Professor LieveVandenBlockoftheEnd-of-LifeCare Research Group, Ghent University & Vrije Universiteit Brussel, Brussels, Belgium. Other partners are: VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; King s College London, Cicely Saunders Institute, London, Cicely Saunders International, London, and International Observatory on End-of-Life Care, Lancaster University, Lancaster, U.K.; Norwegian University of Science and Technology and European Association for Palliative Care Research Network, Trondheim, Norway; Regional Palliative Care Network, IRCCS AOU San Martino-IST, Genoa, and Cancer Research and Prevention Institute, Florence, Italy; European Union Geriatric Medicine Society, Geneva, Switzerland; and Springer Science and Business Media, Houten, The Netherlands. The authors acknowledge the funding from the Economic and Social Research Council (U.K.) (grant no. RES ) with gratitude for a study that inspired this article. The authors declare no conflicts of interest. In recognition of the collaborative nature of EURO IMPACT, the authors thank the following EURO IMPACT members for their contribution, namely: Lieve Van den Block, Koen Meeussen, Augusto Caraceni, Joachim Cohen, Massimo Costantini, Anneke Francke, Richard Harding, Irene Higginson, Stein Kaasa, Karen Linden, Guido Miccinesi, Bregje Onwuteaka- Philipsen, Koen Pardon, Roeline Pasman, Sophie Pautex, and Luc Deliens. They also thank Dr. Jenny Brine (subject librarian at Lancaster University) for her contribution in developing the list of key words to be used for database searching. References 1. Ventafridda V, Ripamonti C, De Conno F, Tamburini M, Cassileth BR. Symptom prevalence and control during patients last days of life. J Palliat Care 1990;6:7e Morita T, Tsunoda J, Inoue S, Chihara S. Do hospice clinicians sedate patients indenting to hasten death? J Palliat Care 1999;15:20e Peruselli C, Di Giulio P, Toscani F, et al. Home palliative care for terminal cancer patients: a survey on the final week of life. Palliat Med 1999;13: 233e Fainsinger RL, Waller A, Bercovici M, et al. A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients. Palliat Med 2000;14:257e Chiu T, Hu W, Lue B, Cheng S, Chen C. Sedation for refractory symptoms of terminal cancer patients in Taiwan. J Pain Symptom Manage 2001;21: 467e Cameron D, Bridge D, Blitz-Lindeque J. Use of sedation to relieve refractory symptoms in dying patients. S Afr Med J 2004;94:445e Cherny NI, Portenoy RK. Sedation in the management of refractory symptoms: guidelines for evaluation and treatment. J Palliat Care 1994;10:31e38.

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