Article Text

Palliative sedation determinants: systematic review and meta-analysis in palliative medicine
  1. Fang Tan1,2,
  2. Na Li1,2,
  3. Yan Wu1,2 and
  4. Chuan Zhang1,2
  1. 1Department of Palliative Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
  2. 2Medicine Research Center, West China-PUMC C.C. Chen Institute of Health, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
  1. Correspondence to Chuan Zhang, Department of Palliative Medicine, West China Fourth Hospital Sichuan University, Chengdu, Sichuan, China; 331273145{at}qq.com

Abstract

Background The utilisation of palliative sedation is often favoured by patients approaching end of life due to the presence of multiple difficult-to-manage symptoms during the terminal stage. This study aimed to identify the determinants of the use of palliative sedation.

Methods To identify pertinent observational studies, a comprehensive search was performed in PubMed, Embase, Cochrane Library, and PsycINFO databases from their inception until March 2022. The methodological quality of the chosen prospective and retrospective cohort studies was assessed using the Newcastle Ottawa Scale, while the Agency for Healthcare Research and Quality was used to evaluate the methodological quality of the selected cross-sectional studies. For each potential determinant of interest, the collected data were synthesised and analysed, and in cases where data could not be combined, a narrative synthesis approach was adopted.

Results A total of 21 studies were analysed in this research, consisting of 4 prospective cohort studies, 7 retrospective cohort studies, and 10 cross-sectional studies. The findings indicated that several determinants were significantly associated with palliative sedation. These determinants included younger age, male gender, presence of tumours, dyspnoea, pain, delirium, making advanced medical end-of-life decisions, and dying in a hospital setting.

Conclusions The findings of our review could help physicians identify patients who may need palliative sedation in advance and implement targeted interventions to reverse refractory symptoms, develop personalized palliative sedation programs, and ultimately improve the quality of palliative care services.

Trial registration PROSPERO registration number CRD42022324720.

  • terminal care
  • cancer
  • hospice care
  • end of life care
  • nursing home care

Data availability statement

Data are available on reasonable request by emailing Fang Tan (email address: 171633168@qq.com).

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Palliative sedation is the last resort for end-stage patients suffering from intractable painful symptoms.

  • The subject of palliative sedation remains controversial.

  • Uncertainty exists about the determinants of palliative sedation within the context of palliative care.

WHAT THIS STUDY ADDS

  • The determinants of palliative sedation are multifaceted.

  • Palliative sedation is more likely to be associated with patients who are younger, male, suffering from a neoplasm, experiencing dyspnoea, pain, delirium, have advance medical end-of-life decisions in place, and are likely to die in a hospital.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Future studies should use high-quality, prospective, multicentre and even transnational cohort studies.

  • Limited evidence can assist in identifying high-risk palliative sedation patients in advance, enabling the development of nursing care plans ahead of time, and providing quality services.

Introduction

During the final stage of life, patients in the advanced phase of illness often endure severe pain symptoms that stem from physical, psychological and spiritual factors. These symptoms may persist despite conventional interventions and can potentially worsen the patient’s overall discomfort. In such cases, palliative sedation may be considered as a viable option.1–3 Palliative sedation involves the administration of sedative medications to reduce a dying patient’s level of consciousness, thereby alleviating otherwise unmanageable refractory symptoms.4–7 The European Association for Palliative Care (EAPC) defines palliative sedation as the cautious use of drugs aimed at inducing a state of reduced consciousness or unconsciousness, with the objective of mitigating intractable suffering in a morally acceptable manner for patients, families and healthcare providers (EAPC, p. 581).3 Palliative sedation can be administered intermittently or continuously until the patient’s death, and the level of sedation can be categorised as mild, moderate or deep following the use of sedatives to address pain.8

Despite the widespread implementation of palliative sedation treatment worldwide, there are ongoing controversies surrounding its ethical considerations, potential dual effects, specific implementation protocols, depth of sedation and the attitudes of healthcare professionals.9–13 Nonetheless, these debates do not impede the progress and utilisation of palliative sedation treatment. The use of this approach not only minimises patients’ pain but also provides support to healthcare professionals who face the challenges of managing refractory pain symptoms in the final stages of illness. However, there is limited research exploring the potential determinants associated with palliative sedation.14 Identifying the relevant determinants of palliative sedation can facilitate early identification of high-risk patients with refractory pain symptoms, as well as highlight the barriers to implementing palliative sedation treatment. This knowledge can further aid in the development of comprehensive care plans aimed at minimising pain in patients with refractory symptoms at the end of life while maximising the preservation of their dignity.

Therefore, the objective of this study is to conduct a systematic review and meta-analysis of existing literature to identify potential determinants of palliative sedation.

Methods

The present study adhered to the reporting guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.15 The comprehensive study protocol was registered prospectively at the International Prospective Register of Systematic Reviews (registration number CRD42022324720).

Identification and selection of studies

In late March 2022, a systematic and computerised literature search was conducted by a medical research librarian (NL) using the databases PubMed, Embase, Cochrane Library and PsycINFO . The search encompassed studies published without any restriction on the start date. The search results were limited to studies published in the English language. The search terms and combinations used were as follows: ((palliative care) OR palliat* OR hospice* OR (end of life) OR (terminal* near/6 care) OR caring OR ill* OR (terminal-stage*) OR dying OR (close near/6 death) OR (end-stage*) OR (near/6 disease*)) AND ((sedation OR sedat* OR (sedative agent) OR (hypnotic sedative agent) OR (palliative sedation)). The detailed search strategy employed for the Cochrane Library is provided in the supplementary materials (online supplemental table 1). Additionally, relevant studies and reviews were identified by manually searching the reference lists of eligible studies. It should be noted that the search will not be repeated prior to the final analysis, and unpublished studies will not be included in the review.

Supplemental material

Study eligibility and inclusion/exclusion criteria

The study selection process was conducted in two stages, independently performed by two reviewers (FT and CZ). Initially, the reviewers screened the titles and abstracts of the articles to determine their potential eligibility. Subsequently, the full texts of the identified articles were assessed for final inclusion. In the event of any disagreements or discrepancies during the screening and selection process or during data extraction, a third independent reviewer (YW) was consulted to resolve them.

Study selection criteria included: (A) Observational studies encompassing cross-sectional and cohort designs, (B) Studies focused on palliative sedation in various palliative care settings, including inpatient palliative care units, independent inpatient palliative care institutions, hospital palliative care teams, community palliative care services and nursing centres, (C) Studies comparing two groups: a sedation group and a non-sedation group, (D) Investigations examining determinants of palliative sedation, and (E) Studies using quantitative analysis methods. Studies were excluded when they did not meet these inclusion criteria. Excluded from the analysis were patients receiving sedation in an intensive care unit, patients under mechanical ventilation and patients undergoing surgical procedures. Additionally, review articles, meta-analyses, commentaries, letters, opinion pieces, editorials, conference articles, case reports and case series were excluded from consideration.

Data extraction and risk of bias assessment

Two independent reviewers (FT and NL) were responsible for extracting data from all eligible studies. In the event of any disagreements, the article in question was re-evaluated and discussed to achieve consensus. If necessary, a third researcher (YW) was consulted to resolve any discrepancies. In instances where relevant information was not available in the published article, attempts were made to contact the authors directly. The EndNote X9 software was used to import and screen the retrieved articles for eligibility. Information from the selected articles was then extracted within the EndNote X9 software. The extracted information encompassed details such as the first author’s name, country, publication year, number of patients, age and gender distribution of the patients, study design, prevalence or incidence of palliative sedation, definition of palliative sedation, and potential determinants associated with sedation.

To assess the risk of bias, the Newcastle-Ottawa Quality Assessment Scale (NOS) was employed for cohort studies,16 17 following the recommendations of the Cochrane Collaboration Group (2021). The NOS was used to evaluate selection, comparability and outcome biases. Scores ranged from 0 to 9 for cohort studies, with scores of 4 indicating a high risk of bias, scores of 5–6 indicating a moderate risk of bias, and scores of 7 indicating a low risk of bias.18 For cross-sectional studies, the risk of bias was assessed using the Agency for Healthcare Research and Quality criteria, which consisted of a total of 11 items. Each item received a score of ‘0’ if answered ‘NO’ or ‘UNCLEAR’, and a score of ‘1’ if answered ‘YES’. The quality of the articles was categorised as follows: low quality (0–3), moderate quality (4–7) and high quality (8–11).

Statistical analysis

To evaluate the clinical and methodological heterogeneity, a decision was made regarding the feasibility of conducting a meta-analysis. Studies that examined the same determinants were assessed to determine whether univariate or multivariate analyses were appropriate based on the specific circumstances. Meta-analysis was conducted using Review Manager (RevMan, V.5.4 for Windows; The Cochrane Collaboration, Copenhagen, Denmark) software. The primary summary measures used in the review were the OR (95% CI) for dichotomous determinants and the mean difference (95% CI) for continuous determinants. Whenever possible, data were standardised across studies. For studies that only provided ORs and their corresponding 95% CIs, the log OR and SE were calculated for all comparisons, and a generic inverse variance method was employed for meta-analysis. Statistical heterogeneity was assessed using the I2 test. In cases where substantial heterogeneity was observed (I² ≥50%), a random-effects model was used; otherwise, a fixed-effect model was applied. The results were presented using a forest plot. Subgroup analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity. Publication bias in studies with a sample size >10 was assessed using Egger’s test or funnel plots.19

In instances where meta-analysis was not feasible, a narrative synthesis approach was employed. Studies addressing each potential determinant were grouped together, and if feasible, common statistical data across the studies were provided, ultimately leading to a descriptive narrative summary.

Results

Study selection

Initially, a comprehensive search combining a manual review of references and an electronic search yielded a total of 10 015 studies. After removing duplicates, 8078 unique studies remained. Subsequently, through a thorough screening of titles and abstracts, 7735 studies were deemed ineligible and excluded. The full texts of the remaining 343 studies were reviewed in detail. Finally, a total of 21 qualitative studies were identified, out of which 14 studies met the inclusion criteria and were included in the analysis. The flow chart illustrating the study selection process and specific details can be found in figure 1.

Figure 1

PRISMA flowchart of studies included in systematic review.

Study characteristics

Table 1 presents the key characteristics of the 21 studies included in the analysis. These studies comprised 4 prospective cohort studies,8 20–22 7 retrospective cohort studies23–29 and 10 cross-sectional studies.30–39

Table 1

Characteristics of the included studies examining the determinants associated with palliative sedation

The study encompassed a total of 62 422 patients from 12 different countries, with 9699 patients receiving sedation. The included studies consisted of three studies from the Netherlands,20 31 34 two studies from Japan,21 22 Switzerland,33 38 Belgium,32 39 Germany,23 26 Brazil24 28 and South Korea,25 27 one study from the UK,37 one study from Spain,30 one study from Italy,8 one study from China,29 and one study from three countries (Flanders, Belgium, the Netherlands, and the UK).35 Additionally, there was a study conducted in six countries (Belgium, Italy, Denmark, Sweden, Netherlands and Switzerland).36

Most studies were conducted in hospices, nursing homes or specialised inpatient palliative care units within hospitals,8 20–23 25 28 31 34 or in hospitals,24 university hospitals,26 29 34 medical centres,27 or public and private hospitals.30 Furthermore, six studies were national cross-sectional stratified death surveys conducted in their respective countries or regions.32 33 35 38 39 One study involved a cross-sectional questionnaire survey targeting doctors across the country.37

In 14 studies, the participants included both individuals with tumours and those without,8 20 23 26 30–39 while the remaining 7 studies focused solely on patients with tumours.21 22 24 25 27–29 Six studies had a minimum age requirement of ≥1 year,32 33 35 36 38 39 one study did not impose any age restrictions,37 six studies included individuals aged ≥16 years,8 20–23 26 and the age range was not reported in eight studies.24 25 27–31 34

Among the included studies, seven employed single or multivariate methods to report on sedation or determinants of sedation.30 32–36 38 Four studies used multiple logistic regression to report determinants of sedation,20 23 31 37 while the remaining four studies conducted quantitative analyses of sedation practices.26 27 29 39

Regarding studies that partially overlapped in sample population and presented similar results, one study was selected for analysis to avoid duplication.33 38

Risk of bias within individual studies

The assessment of the risk of bias is detailed in online supplemental tables 2 and 3. In the cross-sectional studies, the risk of bias ranged from low to moderate (5–8 points). All studies reported the data source (item 1), identified the study population (item 4) and provided specific time identification (item 3). Seven studies (70%) explicitly stated the inclusion and exclusion criteria (item 2).30–33 36 38 39 None of the studies clearly addressed whether evaluators’ subjective factors masked other aspects of the study subjects (item 5) or described any quality assurance assessments (item 6). Additionally, since these were cross-sectional studies, none of them had follow-up assessments (item 11). Moreover, each study appropriately measured and adjusted for key potential confounding variables (item 8). Six studies explained how they dealt with data loss situations (item 9),31 33–35 37 39 and seven studies provided explanations for excluding patients from the analysis (item 7).31–34 37–39

The overall risk of bias in the cohort studies ranged from moderate to low (5–8 points). All studies ensured that the samples truly represented patients with limited life expectancy (item 1). Participants were recruited from the same city, community or country (item 2), and fixed archival measurement methods were used to evaluate sedation and non-sedation (item 3). None of the studies could conclusively prove the absence of the outcomes of interest at the beginning of the study (item 4). Regarding comparability between groups, four studies ensured comparability by controlling for the most important confounders as well as other confounders.14 21 22 25 For the evaluation of outcome events, although there was no independent blinded assessment, all nine studies had corresponding archival records and diagnostic criteria as the basis for assessment.8 20–27 Finally, in terms of cohort follow-up, the loss of subjects was ≤20% in eight studies, or the follow-up was complete.20–23 25–27 29

Potentially relevant determinants

Patient and their disease-related determinants.

Demographic variables

Age

A meta-analysis of seven studies21–23 25 27 28 30 examining the mean age differences revealed a significant association between younger age and the utilisation of palliative sedation (OR: –3.57, 95% CI –6.56 to –0.58) (figure 2A). However, there was substantial heterogeneity (I2=98%, p<0.00001). To account for variations in age across different continents, subgroup analysis was conducted based on continent-specific data from each study, resulting in improved heterogeneity (I2=0%, p=0.75) (figure 3). Additionally, four studies31 35–37 that were not included in the meta-analysis also reported a higher association between younger age and sedation.

Figure 2

Forest plots of meta-analysis of relevant determinants for palliative sedation in the palliative care. (A) Age (years,mean difference) (B) Sex (Male/female,the inverse variance method) (C) Malignant (dichotomous) (D) Dyspnoea (the inverse variance method) (E) MELD (dichotomous) (F) Place death (hospital,the inverse variance method).

Figure 3

Age (years) and sedation (mean difference) in subgroup analyses by different continents.

Sex (male/female)

The meta-analysis using the inverse variance of four studies20 31 36 37 demonstrated a stronger association between male gender and the utilisation of palliative sedation (OR: 1.17, 95% CI 1.05 to 1.31, p=0.004, I2=22%, p=0.28) (figure 2B). Furthermore, in one study that was not included in the analysis,35 the results from multivariate logistic regression analysis indicated a significant likelihood of male patients receiving continuous deep sedation (CDS) until death.

Type of disease

Malignant diseases

The analysis of summary data from four studies20 23 26 33 (figure 2C) indicated a stronger association between patients with cancer and the utilisation of palliative sedation when compared with patients without cancer (OR: 1.39, 95% CI 1.20 to 1.61, p<0.00001; I² = 34%, p=0.21). Moreover, the results from three additional studies30 36 37 that were not included in the meta-analysis aligned with these findings.

Symptoms

Dyspnoea

The meta-analysis using the inverse variance of two studies34 39 revealed a higher likelihood of patients with dyspnoea receiving sedation (OR: 1.77, 95% CI 1.61 to 1.94, p<0.00001, I² = 0%, p=0.51) (figure 2D). Additionally, 11 studies8 21 22 24–28 30 that were not included in the meta-analysis consistently reported that patients with dyspnoea were more prone to receiving sedation when compared with patients with other refractory symptoms.

Delirium

Papavasiliou et al39 found a significant association between delirium and sedation, with an OR of 3.00 (95% CI 1.73 to 5.21, p<0.001). Additionally, seven studies8 22 23 25–27 consistently identified delirium as a prevalent and primary factor leading to the administration of sedation.

Pain

Papavasiliou et al39 highlighted that patients experiencing pain were more likely to receive sedation, with an OR of 2.66 (95% CI 1.38 to 5.14, p=0.002). Additionally, five studies8 22 25 27 28 provided descriptive evidence supporting pain as a determinant of sedation.

Existential suffering

van Deijck et al31 provided insights into the characteristics of patients with existential suffering who received continuous palliative sedation (CPS). de Araujo28 reported that 7.6% of sedated patients exhibited psychological distress that warranted palliative sedation.

Others

Opioid used

van Deijck et al20 conducted multivariate logistic regression analysis, which revealed a significant association between the use of opioids at admission and the administration of CDS (OR: 1.90, 95% CI 1.18 to 3.05, p=0.008).

Decision making

Medical end-of-life decisions

The summarised findings from two studies37 38 indicated (figure 2E) that patients who had made advanced medical end-of-life decisions (MELDs) were more likely to receive sedation (OR: 3.67, 95% CI 2.93 to 4.60, p<0.00001, I2=0%, p=0.96).

Attitudes towards euthanasia or in favour of assisted dying

van Deijck et al31 found that patients who required euthanasia due to refractory symptoms had a higher likelihood of receiving sedation (OR: 2.93; 95% CI 1.37 to 6.26, p=0.01). Additionally, Seale et al37 suggested that CDS was associated with a higher rate of requests from patients or their relatives for hastened death (OR: 1.22, 95% CI 1.10 to 1.36, p<0.001).

Medical environment

Place of death

Place (hospital)

The meta-analysis using inverse variance of three studies36–38 (figure 2F) revealed that patients in hospital settings had a higher likelihood of receiving sedation (OR: 1.57, 95% CI 1.42 to 1.74, p<0.00001, I2 = 0%, p=0.37). Additionally, Anquinet et al35 reported a significant association between hospitalisation and sedation use (OR: 1.00, 95% CI 1.00 to 1.00). Furthermore, four studies23 27 32 33 highlighted variations in sedation practices across different care settings.

Physician

Medical expertise and experience

Four studies27 33 37 39 have examined the influence of physician specialty on palliative sedation. Ziegler et al33 found that doctors with more experience in caring for dying patients were more likely to administer sedation (OR: 1.8, 95% CI 1.2 to 2.7, p=0.004), as well as doctors with greater experience in end-of-life care (OR: 1.6, 95% CI 1.0 to 2.7, p=0.054). Papavasiliou et al39 reported that medical specialists reported a higher frequency of sedation use compared with general practitioners.

Attitude towards assisted death and religious faith

Seale et al37 found that doctors who supported euthanasia or physician-assisted suicide (PAS), or those who had no religious beliefs, were more inclined to administer CDS.

Discussion

Summary of main findings

Our systematic review and meta-analysis have revealed the complexity of determinants associated with palliative sedation. Regarding patient-related determinants, evidence suggests that younger age, male gender, neoplastic diseases, dyspnoea, pain and delirium are more likely to be associated with palliative sedation. However, the association between opioid use and palliative sedation was reported in only one study. Palliative sedation related to existential suffering was found to be more common in patients with specific chronic and incurable diseases.

Regarding medical decision-making, patients who made MELDs were more likely to receive palliative sedation. Among these patients, those with tumours, younger age and decision-making capacity were more prone to making MELDs, thus, leading to higher utilisation of palliative sedation.

In terms of the healthcare environment, evidence suggests that patients in hospital settings are more likely to receive palliative sedation compared with those in other settings, such as home or nursing homes. Furthermore, the physician’s specialty, medical experience, religious beliefs and attitudes towards palliative sedation have been found to influence the administration of palliative sedation.

Strengths and limitations of the review

Our study has several strengths. First, it is the first comprehensive systematic review and meta-analysis examining the determinants of palliative sedation. Our literature search followed strict selection criteria, ensuring the inclusion of relevant studies. Additionally, the screening and risk of bias assessment were conducted independently by two reviewers, enhancing the reliability of the meta-analysis findings. However, our study has some limitations that should be acknowledged.

First, some studies did not prioritise determinants of palliative sedation as their primary outcome. Additionally, certain studies provided only cross-sectional data or conducted secondary data analyses on indicators associated with determinants of palliative sedation. As a result, these studies may not have specifically addressed our research questions. Second, determinants reported in only one study may not provide strong evidence without additional information and replication. Third, survey results, particularly those from cross-sectional studies, were reliant on information provided by general practitioners or specialists regarding patients who died in the hospital. This reliance on investigators’ reports may have introduced biases, leading to underestimation or overestimation of certain determinants. Fourth, the included studies used different types of sedation, including CDS, continuous sedation (without specifying the depth) and intermittent sedation. Therefore, caution should be exercised when interpreting the comprehensive effects of certain determinants, limiting the generalisability of our findings. Moreover, the design of the included studies varied in terms of ethnic population, medical settings, attending physicians, and legal, cultural, and organisational determinants specific to the countries where the studies were conducted. This further restricts the generalisability of the results.

What this study adds

Currently, there is a significant body of literature on palliative sedation, focusing primarily on ethical considerations, the doctrine of double effect, commentary and practical experiences from different countries. However, there is a paucity of studies that comprehensively analyse the determinants of palliative sedation. While van Deijck et al14 conducted a study on the determinants of palliative sedation, the available literature at that time limited their analysis to descriptive assessments without conducting a meta-analysis. Therefore, our study is the first to employ a meta-analysis approach to examine the determinants of palliative sedation.

Regarding patients and factors related to their diseases, we found that younger patients, particularly those below the age of 60 years or 65 years, were more likely to receive palliative sedation.31 33 35–38 This age difference can be attributed to several factors. First, younger patients with aggressive disease trajectories may seek more intensive interventions, including palliative sedation. Additionally, younger patients, especially those with cancer, are more likely to experience pain and consequently receive pain medication.40 The presence of pain increases the likelihood of considering and opting for palliative sedation.39 On the other hand, elderly patients may have reduced consciousness in the final days of life, hindering their ability to express pain symptoms. Furthermore, pain assessment may be underestimated in elderly patients, particularly those with Alzheimer’s disease, due to challenges in evaluating their pain levels.41 De Gendt et al32 reported that physician-assisted dying occurred less frequently among very old patients and highlighted the association between providing CDS and physicians’ attitudes towards assisted dying and religious beliefs.37

Sex is another determinant of palliative sedation, and the differences can be reasonably explained. Female patients tend to be more willing to express and communicate their emotions due to diverse life trajectories and gender characteristics. This willingness to communicate can contribute to better symptom control. In contrast, male patients, who often suppress their emotions and receive less social support in the final stages of life, may experience more severe symptoms that necessitate palliative sedation.42

Miccinesi et al36 suggest that palliative sedation is more prevalent among patients with cancer. This can be attributed to the more aggressive disease trajectory and refractory pain symptoms commonly experienced by patients with cancer, which increase the likelihood of considering and receiving palliative sedation. Moreover, compared with individuals with chronic diseases in the general end-stage population, some patients with cancer have a better understanding of their disease progression and are more likely to make advanced MELDs in the terminal stages of their illness.34

Refractory symptoms at the end of life commonly include dyspnoea, delirium, pain and anxiety.43 Existential suffering is also recognised as a prevalent symptom among terminally ill patients.44 Consistent with the framework of palliative sedation recommended by EAPC and the most commonly reported symptoms by Cherny et al,3 our study confirms that palliative sedation is more likely to be administered to patients experiencing dyspnoea, delirium and pain. The concept of existential suffering at the end of life encompasses various aspects such as loss of personal meaning, loss of life’s purpose, fear of death, feelings of despair, anguish, and hopelessness, perception of being a burden to others, loss of dignity, sense of helplessness, and a sense of betrayal.45 However, there is still no clear consensus on whether patients with existential suffering should receive palliative sedation, as there are differences in the identification and understanding of existential suffering.6 46 van Deijck et al31 found a positive correlation between the administration of palliative sedation for existential suffering and certain patient characteristics, particularly the nature of the underlying disease. For instance, rapidly progressive neurological diseases like amyotrophic lateral sclerosis may induce fear and lead to refractory symptoms.47 Another study by van Deijck20 reported an independent positive association between CDS and the use of opioids on admission. This can be explained by the fact that patients prescribed opioids often experience pain or dyspnoea, which are potential determinants for palliative sedation. Moreover, the use of opioids may induce delirium, which could necessitate palliative sedation.

In terms of medical decision-making, Seale et al37 reported that cases of CDS were more likely to coincide with other end-of-life decisions involving the intention to hasten death. However, the presence of these cases does not necessarily imply that CDS was administered with the intent to hasten death. Additionally, CDS cases were associated with a higher rate of requests for a hastened death, but this alone does not constitute evidence that CDS was a response to such requests. Common guidelines emphasise that palliative sedation should be used solely for refractory symptoms and should be clearly distinguished from decisions that may shorten life.48 Nonetheless, the conceptual distinction between CDS until death and medically assisted life-ending decisions remains challenging. Many healthcare professionals grapple with this distinction.49 van Deijck et al31 reported a positive correlation between euthanasia requests and the decision to initiate CPS, suggesting that such requests may influence the use of CPS even in cases where euthanasia would be more appropriate.

According to clinical guidelines, the decision to administer CDS until death involves a multidisciplinary process,3 which can vary across different medical environments due to the availability of medical resources.50 Our findings indicate that palliative sedation is more commonly used in hospital settings compared with other locations.36–38 Notably, in Belgium, CDS occurred less frequently in home deaths compared with hospital deaths.36 This may be attributed to the preference of patients with severe symptoms to receive treatment and end-of-life care in a hospital setting, where they may have greater access to frequent palliative sedation.51–53 Furthermore, the challenges in providing CDS at home may be exacerbated by limited resources.54 Various factors related to healthcare professionals, such as specialty, medical experience, religious beliefs and attitudes towards palliative sedation, can influence its utilisation. For instance, in the Netherlands, general practitioners were less likely to report cases of CDS compared with hospital specialists.55 Seale et al37 found that doctors who support the legalisation of euthanasia or PAS and those who are non-religious were more likely to report cases of CDS. This suggests that the decision to administer CDS may be influenced by attitudes that are conducive to medical actions that potentially hasten death. It is important to note that differences in the utilisation of CPS among physicians in different specialties may be influenced by factors such as country-specific medical policies, physician expertise, the local development of palliative care and public understanding of palliative sedation.

Conclusion

Although our study has identified several determinants of palliative sedation, there are limitations that need to be considered. The number of articles available on this topic is limited, and there are variations in study design and complex legal, cultural and organisational factors across different countries. These variations may reflect differences in the quality of hospice care among countries. Palliative sedation is a complex decision-making process that involves multiple disciplines and is influenced not only by patients’ refractory symptoms and the medical resources available for palliative sedation but also by the experience of healthcare professionals, religious beliefs, public attitudes and understanding of palliative sedation, and the overall development of national palliative care.

Future research should focus on improving the knowledge and expertise of healthcare professionals in this area. It is important to establish standardised definitions and guidelines for the application of palliative sedation. High-quality prospective studies, multicentre studies and even transnational cohort studies are needed to investigate the determinants of palliative sedation in a comprehensive and reliable manner. Multivariate analysis should be employed to adjust for important confounding determinants. This will enable healthcare professionals, particularly those specialised in palliative care, to develop comprehensive and individualised care plans, including the consideration of palliative sedation at an early stage of palliative care for patients nearing the end of life. Additionally, appropriate interventions should be implemented to manage severe pain symptoms in patients. If these symptoms cannot be effectively alleviated, the necessity of palliative sedation should be carefully determined.

Data availability statement

Data are available on reasonable request by emailing Fang Tan (email address: 171633168@qq.com).

Ethics statements

Patient consent for publication

Acknowledgments

The authors thank Duan Guo (Colleague of the author, West China School of Public Health and West China Fourth Hospital, Sichuan University) for her essential contribution to statistical support.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Contributors FT and NL contributed to the conception and design of the study. FT, CZ and YW selected papers for review. FT, NL and YW participated in data extraction and were responsible for the selection and quality assessment of the study. FT and CZ drafted the article. All authors contributed to the revision of the manuscript, and read and approved the submitted version. FT acts a guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.