BACKGROUND: Clinical experts experienced challenges in the practice of palliative sedation (PS) during the COVID-19 pandemic. Rapid deterioration in patients\' situation was observed while the indications for starting PS seemed to differ compared to other terminal patients. It is unclear to which extent clinical trajectories of PS differ for these COVID patients compared to regular clinical practice of PS.
OBJECTIVE: To describe the clinical practice of PS in patients with COVID versus non-COVID patients.
METHODS: A retrospective analysis of data from a Dutch tertiary medical centre was performed. Charts of adult patients who died with PS during hospitalisation between March \'20 and January \'21 were included.
RESULTS: During the study period, 73 patients received PS and of those 25 (34%) had a COVID infection. Refractory dyspnoea was reported as primary indication for starting PS in 84% of patients with COVID compared to 33% in the other group (p < 0.001). Median duration of PS was significantly shorter in the COVID group (5.8 vs. 17.1 h, p < 0.01). No differences were found for starting dosages, but median hourly dose of midazolam was higher in the COVID group (4.2 mg/hr vs. 2.4 mg/hr, p < 0.001). Time interval between start PS and first medication adjustments seemed to be shorter in COVID patients (1.5 vs. 2.9 h, p = 0.08).
CONCLUSIONS: PS in COVID patients is characterized by rapid clinical deterioration in all phases of the trajectory. What is manifested by earlier dose adjustments and higher hourly doses of midazolam. Timely evaluation of efficacy is recommended in those patients.

Palliative Sedation (PS) is an effective measure for the relief of refractory symptoms in end-of-life patients. This intervention can be performed at home, respecting the patients\' and their families\' decisions. A scoping review was performed to map the available evidence in the literature on the performance of PS at home. This review included 23 studies. Most were conducted in European countries with adult cancer patients. Patients, family members and healthcare providers participated in the decision making regarding the use of PS at home. PS was used primarily to manage refractory symptoms (pain, delirium, dyspnea, and others), and in 1 of the studies PS was mentioned as a possible intervention for shortening life. The most commonly used medication was midazolam and the average duration ranged from 4 h to 7 days. There are few reports on adverse events related to PS. This intervention seems to be a feasible possibility for the management of refractory symptoms in patients at the end of life, despite the fact that it can represent specific challenges for healthcare providers, patients and families. However, the literature is limited regarding PS in children and in people with diseases other than cancer, as well as on the evaluation of possible adverse effects related to this intervention. Furthermore, it is essential to have a broad ethical, clinical and legal debate on whether to consider the use of PS for the purpose of shortening life in specific cases.

Palliative sedation can be considered as \"the last resort\" in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. The aim is symptom relief and not to induce death as in the case of euthanasia. The treatment might be one of the most challenging therapeutic options in the field of palliative care, involving both ethical and practical issues. Still, studies have shown that it is a safe and valuable treatment and in general does not shorten the life of the patient. Since patients in Switzerland have the legal option of assisted suicide, palliative sedation is an alternative that has become increasingly important. The use of palliative sedation was reported in 17.5% of all patients admitted to palliative care in Switzerland, making the country of those with the highest use of this treatment. The aim of this narrative review is to discuss ethical and practical issues in palliative sedation, with specific focus on experiences from Switzerland. Indications, ethical considerations, drugs of choice and duration are discussed. Decision making should be based on solid guidelines. When used correctly, palliative sedation is an important and useful tool in palliative care in order to provide good symptom relief.

BACKGROUND: The involvement of patients in decision making about their healthcare plans is being emphasized. In the context of palliative sedation, it is unclear how these decisions are made and who are involved in. The aim of the study is to understand how this decision-making is taken.
METHODS: Information from a systematic review on clinical aspects of palliative sedation prospective studies were included. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014-December 2019). Data extraction and analysis regarded: (a) When and by whom the decision-making process is initiated; (b) patient involvement; (c) family involvement and (d) healthcare involvement.
RESULTS: Data about decision making were reported in 8/10 included articles. Palliative sedation was reported in 1137 patients (only 16 of them were non-cancer). Palliative sedation was introduced by the palliative care team during the disease process, at admission, or when patients experienced refractory symptoms. Only two studies explicitly mentioned the involvement of patients in decision making. Co-decision between families and the regular health care professionals was usual, and the health care professionals involved had been working in palliative care services.
CONCLUSIONS: Patient participation in decision making appeared to be compromised by limited physical or cognitive capacity and family participation is described. The possibility of palliative sedation should be discussed earlier in the disease process.

UNASSIGNED: Patients approaching end of life may experience intractable symptoms managed with palliative sedation. The legalization of Medical Assistance in Dying (MAiD) in Canada in 2016 offers a new option for relief of intolerable suffering, and there is limited evidence examining how the use of palliative sedation has evolved with the introduction of MAiD.
UNASSIGNED: To compare rates of palliative sedation at a tertiary care hospital before and after the legalization of MAiD.
UNASSIGNED: This study is a retrospective chart analysis of all deaths of patients followed by the palliative care consult team in acute care, or admitted to the palliative care unit. We compared the use of palliative sedation during 1-year periods before and after the legalization of MAiD, and screened charts for MAiD requests during the second time period.
UNASSIGNED: 4.7% (n = 25) of patients who died in the palliative care unit pre-legalization of MAiD received palliative sedation compared to 14.6% (n = 82) post-MAiD, with no change in acute care. Post-MAiD, 4.1% of deaths were medically-assisted deaths in the palliative care unit (n = 23) and acute care (n = 14). For patients who requested MAiD but instead received palliative sedation, the primary reason was loss of decisional capacity to consent for MAiD.
UNASSIGNED: We believe that the mainstream presence of MAiD has resulted in an increased recognition of MAiD and palliative sedation as distinct entities, and rates of palliative sedation increased post-MAiD due to greater awareness about patient choice and increased comfort with end-of-life options.

Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed, but they are mainly based on expert opinion or retrospective chart reviews. Therefore, evidence for the clinical aspects of palliative sedation is needed.
To explore clinical aspects of palliative sedation in recent prospective studies.
Systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at PROSPERO. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014-December 2019), combining sedation, palliative care, and prospective. Article quality was assessed.
Ten prospective articles were included, involving predominantly patients with cancer. Most frequently reported refractory symptoms were delirium (41%-83%), pain (25%-65%), and dyspnea (16%-59%). In some articles, psychological and existential distress were mentioned (16%-59%). Only a few articles specified the tools used to assess symptoms. Level of sedation assessment tools were the Richmond Agitation Sedation Scale, Ramsay Sedation Scale, Glasgow Coma Scale, and Bispectral Index monitoring. The palliative sedation practice shows an underlying need for proportionality in relation to symptom intensity. Midazolam was the main sedative used. Other reported medications were phenobarbital, promethazine, and anesthetic medication-propofol. The only study that reported level of patient\'s discomfort as a palliative sedation outcome showed a decrease in patient discomfort.
Assessment of refractory symptoms should include physical evaluation with standardized tools applied and interviews for psychological and existential evaluation by expert clinicians working in teams. Future research needs to evaluate the effectiveness of palliative sedation for refractory symptom relief.

The use of continuous sedation until death (CSD) has been highly debated for many years. It is unknown how the use of CSD evolves over time. Reports suggest that there is an international increase in the use of CSD for terminally ill patients.
To gain insight in developments in the use of CSD in various countries and subpopulations.
We performed a search of the literature published between January 2000 and April 2020, in PubMed, Embase, CINAHL, PsycInfo, and the Cochrane Library by using the Preferred reporting items for systematic review and meta-analysis protocols guidelines. The search contained the following terms: continuous sedation, terminal sedation, palliative sedation, deep sedation, end-of-life sedation, sedation practice, and sedation until death.
We found 23 articles on 16 nationwide studies and 38 articles on 37 subpopulation studies. In nationwide studies on frequencies of CSD in deceased persons varied from 3% in Denmark in 2001 to 18% in The Netherlands in 2015. Nationwide studies indicate an increase in the use of CSD. Frequencies of CSD in the different subpopulations varied too widely to observe time trends. Over the years, more studies reported on the use of CSD for nonphysical symptoms including fear, anxiety, and psycho-existential distress. In some studies, there was an increase in requests for sedation of patients from their families.
The frequency of CSD seems to increase over time, possibly partly because of an extension of indications for sedation, from mainly physical symptoms to also nonphysical symptoms.

BACKGROUND: Palliative sedation is defined as monitored use of medication intended to induce a state of decreased or absent awareness to relieve intractable suffering in a manner that is ethically acceptable to the patient, family, and health-care providers. The prevalence of palliative sedation reported ranges from 10% to 50% during in end of life care setting. There was no major review performed on the prevalence and practice of palliative sedation in Hong Kong. Besides, published guidelines and medication recommendations are developed in Caucasian settings, which may not be taken into account the cultural aspect in Chinese. Therefore, we would like to review our practice in caring terminal cancer patients to report the prevalence and practice of palliative sedation and to review factors associated with successful sedation in this group of patients.
METHODS: One-hundred and eighty consecutive patients with histological or radiological evidence of malignancy who died in palliative care ward from 1st July to 30th September 2017 were screened. All patients who received continuous midazolam infusion were included. Patients\' demographic data, cancer disease status, laboratory results and interview records were retrieved from electronic patient records and in-patient hospital notes. The reason for sedation, background and concurrent symptoms during sedation, and the clinical notes on symptom control during the sedation period were all reviewed. All the drug records including the dose of midazolam and other concomitant drugs, duration of palliative sedation as well as the depth of sedation were assessed. Survival data estimated from the day of admission to our department until death were recorded.
RESULTS: Three hundred and thirty-nine patient-days, contributed by 81 patients out of 180 patients (45%), with midazolam infusion were studied. There was no statistical difference in the baseline characteristics of both patient groups. Median survival since admission to oncology ward in the sedated group was 11 versus 9 days in the non-sedated group (P=0.65). The median time for patients on sedation was 32.33 hours (range, 2.91-1,240 hours). Dyspnea was the most common cause of palliative sedation (78.0%), followed by delirium (40.9%). The mean dose of midazolam infusion was 10 milligram per day (range, 5-45 mg). Deranged liver function was the only statistically significant factor associated with successful sedation after multivariate analysis.
CONCLUSIONS: The use of palliative sedation is safe and effective in managing refractory symptoms and is not associated with worsening of survival. Deranged liver function was associated with better symptom control. The dose of midazolam and haloperidol needed for adequate symptom control were lower than suggested in Western guidelines. Further studies on the dose requirement in Chinese population are warranted. Establishing consensus and guidelines on palliative sedation in Hong Kong should be the way forward to ensure quality care to this group of patients.

BACKGROUND: Palliative sedation for existential suffering (PS-ES) is a controversial clinical intervention. Empirical studies about physicians\' perceptions do not converge in a clear position and current clinical practice guidelines do not agree either regarding this kind of intervention.
OBJECTIVE: To gain deeper insight into physicians\' perceptions of PS-ES, the factors influencing it, the conditions for implementing it and the alternatives to it.
METHODS: Systematic review of qualitative, quantitative and mixed-methods studies following the Peer Review Electronic Search Strategies and Preferred Reporting Items for Systematic Reviews and Meta-analyses protocols; quality appraisal and thematic synthesis methodology.
METHODS: Seven electronic databases (PubMed, CINAHL, Embase, Scopus, Web of Science, PsycINFO, PsycARTICLES) were exhaustively searched from inception through March 2019. Two reviewers screened paper titles, abstracts and full texts. We included only peer-reviewed journal articles published in English, French, German, Dutch, Spanish, Italian or Portuguese that focused on physicians\' perceptions of PS-ES.
RESULTS: The search yielded 17 publications published between 2002 and 2017. Physicians do not hold clear views or agree if and when PS-ES is appropriate. Case-related and individual-related factors that influenced physicians\' perceptions were identified. There is still no consensus regarding criteria to distinguish between necessary and sufficient conditions for invoking PS-ES. Some alternatives to PS-ES were identified.
CONCLUSIONS: To date, there is still no consensus on physicians\' perceptions of PS-ES. Further research is necessary to understand factors that influence physicians\' perceptions and philosophical-ethical presuppositions underlying this perceptions.

OBJECTIVE: The undesired effects of midazolam can be life-threatening. This paper delineates the findings related to the pharmacokinetics, adverse effects and drug-drug interactions as well as associated therapeutic implications for safe midazolam use.
METHODS: A systematic review of literature was conducted.
RESULTS: The pharmacokinetics of midazolam depends on hepatic and renal functions, fat tissue mass, route and duration of administration, as well as potential drug-drug interactions. Palliative care patients constitute a high-risk group prone to side effects of drugs, due to polytherapy and multi-organ failure.
CONCLUSIONS: Midazolam is one of three most frequently administered drugs in palliative care. The indications for its use include anxiety, dyspnea, seizures, vomiting refractory to treatment, agitation, myoclonus, status epilepticus, restlessness, delirium, pruritus, hiccups, insomnia, analgosedation, palliative sedation and preventing or counteracting undesired effects of ketamine.