Monday, August 24, 2015

Palliative pharmacological sedation for terminally ill adults.



Terminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain, vomiting, and psychological and physical distress. In the terminal phase of life, these symptoms may become refractory, and unable to be controlled by supportive and palliative therapies specifically targeted to these symptoms. Palliative sedationtherapy is one potential solution to providing relief from these refractory symptoms. Sedation in terminally ill people is intended to provide relief from refractory symptoms that are not controlled by other methods. Sedative drugs such as benzodiazepines are titrated to achieve the desired level ofsedation; the level of sedation can be easily maintained and the effect is reversible.


To assess the evidence for the benefit of palliative pharmacological sedation on quality of life, survival, and specific refractory symptoms in terminally ill adults during their last few days of life.


We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 11), MEDLINE (1946 to November 2014), and EMBASE (1974 to December 2014), using search terms representing the sedative drug names and classes, disease stage, and study designs.


We included randomised controlled trials (RCTs), quasi-RCTs, non-RCTs, and observational studies (e.g. before-and-after, interrupted-time-series) with quantitative outcomes. We excluded studies with only qualitative outcomes or that had no comparison (i.e. no control group or no within-group comparison) (e.g. single arm case series).


Two review authors independently screened titles and abstracts of citations, and full text of potentially eligible studies. Two review authors independently carried out data extraction using standard data extraction forms. A third review author acted as arbiter for both stages. We carried out no meta-analyses due to insufficient data for pooling on any outcome; therefore, we reported outcomes narratively.


The searches resulted in 14 included studies, involving 4167 adults, of whom 1137 received palliative sedation. More than 95% of people had cancer. No studies were randomised or quasi-randomised. All were consecutive case series, with only three having prospective data collection. Risk of bias was high, due to lack of randomisation. No studies measured quality of life or participant well-being, which was the primary outcome of the review. Five studies measured symptom control, using four different methods, so pooling was not possible. The results demonstrated that despite sedation, delirium and dyspnoea were still troublesome symptoms in these people in the last few days of life. Control of other symptoms appeared to be similar in sedated and non-sedated people. Only one study measured unintended adverse effects of sedative drugs and found no major events; however, four of 70 participants appeared to have drug-induced delirium. The study noticed no respiratory suppression. Thirteen of the 14 studies measured survival time from admission or referral to death, and all demonstrated no statistically significant difference between sedated and non-sedated groups.


There was insufficient evidence about the efficacy of palliative sedation in terms of a person's quality of life or symptom control. 
There was evidence that palliative sedation did not hasten death, which has been a concern of physicians and families in prescribing this treatment. 
However, this evidence comes from low quality studies, so should be interpreted with caution. 
Further studies that specifically measure the efficacy and quality of life in sedated people, compared with non-sedated people, and quantify adverse effects are required.
[PubMed - in process]
 2009 May;37(5):771-9Nov 28.

Controlled sedation for refractory symptoms in dying patients.


Terminally ill cancer patients near the end of life may experience intolerable suffering refractory to palliative treatment. Although sedation is considered to be an effective treatment when aggressive efforts fail to provide relief in terminally ill patients, it remains controversial. The aim of this study was to assess the need and effectiveness of sedation in dying patients with intractable symptoms, and the thoughts of relatives regardingsedation. A prospective cohort study was performed on a consecutive sample of dying patients admitted to an acute pain relief and palliative care unit within a cancer center. Indications for sedation, opioid and midazolam doses, level of delirium and sedation, nutrition, hydration, rattle, inability to cough and swallow, pharyngeal aspiration, duration of sedation and survival, and use of anticholinergics or other drugs were recorded. Family members were interviewed. Forty-two of 77 dying patients were sedated, and had a longer survival than those who were not sedated (P=0.003). 

Prevalent indications for sedation were dyspnea and/or delirium. Twelve patients began with an intermediate sedation, and 38 patients started with definitive sedation. The median sedation duration was 22 hours. Opioid doses did not change during sedation. Agitated delirium significantly decreased with increasing doses of midazolam, whereas the capacity to communicate concomitantly decreased. Interviewed relatives were actively involved in the process of end-of-life care, and the decision to sedate, and the efficacy of sedation, were considered appropriate by almost all relatives. 

Controlled sedation is successful in dying patients with untreatable symptoms, did not hasten death, and yielded satisfactory results for relatives. This study also points to the importance of palliative care and the experience of professionals skilled in both symptom control and end-of-life care.
[PubMed - indexed for MEDLINE]
 2012 Apr 20;30(12):1378-83. 

Palliative sedation in end-of-life care and survival:            a systematic review.

Erratum in

  • J Clin Oncol. 2012 Sep 20;30(27):3429.



Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival.


A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed.


Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival.


Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting,palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
[PubMed - indexed for MEDLINE]
 2015 Mar 15;14:5.

Palliative sedation for terminally ill cancer patients in a tertiary cancer center in Shanghai, China.



There are a number of studies dedicated to characteristics of sedation, but these studies are mostly bound to western country practices. The aim of this study is to describe the characteristics of patients who suffered from cancer and who had been sedated until their death in Shanghai, China.


Retrospective medical data of 244 terminally ill cancer patients including 82 sedated patients were collected. Data collected included demographic characteristics, disease-related characteristics and details of the sedation.


In sedated cases, patients and/or caregivers gave the consent to start palliative sedation due to unmanageable symptoms. On average,sedation was performed 24.65(±1.78)hours before death. Agitated delirium and dyspnea were the most frequent indications for palliative sedation. There was no significant difference in survival time from admission till death between sedated and non-sedated patients (p > 0.05).


Palliative sedation is effective for reducing terminally ill cancer patients' suffering without hastening death. Prospective research is needed to determine the optimal conditions for Chinese patients including indications, decision making process, informed consent, cultural and ethical issues, type of sedation and drugs.


Agitated delirium; End of life; Palliative sedation; Survival; Symptom management; Terminally ill cancer patients
Free PMC Article
 2015 Aug 13. 

A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease.


A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce transient sedation when emergencies occur in palliative care.

 We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD).
 In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed.
 Thirty patients with cancer and 29 with COPD received at least 1 DP.

 All patients receiving a DP for an appropriate indication were sedated within 30 minutes.
 There was no difference in survival from DP administration among patients who received it and those who did not.
© The Author(s) 2015.


COPD; distress protocol; end-of-life symptoms; lung cancer; palliative crises
[PubMed - as supplied by publisher]

Friday, August 21, 2015

A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease.


A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce
 transient sedation when emergencies occur in palliative care.

 We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD). 

In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed. Thirty patients with cancer and 29 with COPD received at least 1 DP. 

All patients receiving a DP for an appropriate indication were sedated within 30 minutes. There was no difference in survival from DP administration among patients who received it and those who did not.

© The Author(s) 2015.

Wednesday, July 15, 2015

 2010 Sep;57(9):B4184.

Health-related quality of life in early breast cancer.


The treatment of primary breast cancer usually consists of surgery often followed by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to reduce the risk of recurrence. The cancer diagnosis and the treatments may have significant impact on the patients' quality of life. This thesis deals with scientific aspects and clinical results of a study aimed at assessing the impact of breast cancer (and its treatment) on the patients' quality of life. Studies such as this assessing the problems and symptoms experienced by the patients are often referred to as health-related quality of life (HRQL) research. HRQL research deals with subjective experiences and raises challenging, scientific questions. Therefore, much attention was directed towards methodological issues in this clinically motivated project. The study was a prospective, longitudinal, questionnaire-based investigation of women with newly diagnosed breast cancer registered in the Danish Breast Cancer Co-operative Group's DBCG 89 Program. The patients were sub-divided into low-risk and high-risk patients. High-risk patients were offered randomisation in one of three randomised adjuvant therapy trials involving chemotherapy, ovarian ablation, and endocrine therapy. After a literature study and interviews with breast cancer patients, a questionnaire was composed that included two widely used standard questionnaires (EORTC QLQ-C30 and Hospital Anxiety and Depression (HAD) Scale) and a DBCG 89 Questionnaire developed for this study. A total of 1,898 eligible patients were invited by post to participate in the study involving six assessments over a 2-year period, and 1,713 patients (90%) completed the first questionnaire. Furthermore, a questionnaire was sent to 872 women selected at random from the general population; 608 (70%) responded. The multi-item scales of the two standard questionnaires were analysed for so-called differential item functioning (DIF) in order to investigate whether the (summary) scale scores were adequate representations of the information obtained by the individual items. The DIF analyses identified a number of cases of DIF, which, among other things, contributed to detection of possible problems in the HAD Scale. It was concluded that DIF analyses are relevant when important analyses based on multi-item scales are made. A new way to evaluate the validity of questionnaires was developed. The results from questionnaires completed by patients were compared against results from open ended interviews with the same patients rated by observers. The idea was that if results were similar, the patients had then probably understood and completed the questionnaire items as intended. On the other hand, if results from self-assessment and interviews deviated, misunderstandings or other errors might have taken place, and the study would give insight into possible problems. Of 57 breast cancer patients, 46 (81%) were successfully interviewed. In general, the agreement between patient-completed questionnaires and interviews was excellent, indicating very good validity. The median weighted kappa for the EORTC QLQ-C30 was 0.85 (range 0.49-1.00); it was 0.79 (range 0.65-0.95) for the HAD Scale, and 0.92 (range 0.51-1.00) for the DBCG 89 Questionnaire. However, the study identified a mechanism called selective reporting, which may affect results from most HRQL questionnaires: in order to provide correct and useful answers some patients do not report symptoms they believe are irrelevant to the study, e.g., symptoms unrelated to cancer. This mechanism may lead to bias if results from patients are compared to results from populations reporting their symptoms more completely, e.g., general population samples. In contrast, this mechanism has little importance when results from different sub-groups of cancer patients are compared. In this study multiple variables were assessed at multiple points in time and we did not have a priori hypotheses for all these potential comparisons. Therefore, a staff survey involving experienced doctors and nurses was conducted in order to generate hypotheses that could be tested in the data from patients. We contacted 46 health care professionals and 36 (78%) responded. Overall, the staff survey did not prove very useful for the intended purpose. The main reason for this was probably that the health care professionals had limited insight into the patients' HRQL. A different approach to the problem of multiple hypothesis testing proved more useful. Hypotheses generated from the initial literature review were tested in the comparison of patients in chemotherapy against patients not in chemotherapy. The study of women selected at random from the general population showed that these women experienced a considerable degree of "morbidity" according to all three questionnaires. This shows that symptoms and problems reported by cancerpatients may have causes other than cancer, and thus constitutes a good justification for the use of data from general population studies when interpreting data from cancer patients. The levels of anxiety and depression of low-risk breast cancer patients were found to be lower than those from the general population sample. After careful consideration we concluded that this finding was probably incorrect. The most important explanations were thought to be the wording of some HAD Scale items as well as two mechanisms that are not specific to the HAD Scale, the "selective reporting mechanism" found in the validation study, and the response-shift problem. These findings indicate - in contrast to the conclusion above - that the comparability of HRQL data from cancer patients and general population data must be questioned. However, as this is the first study to raise the problem, this issue needs further investigation. Based on the initial literature review and interviews we hypothesised that 30 different HRQL issues would be impaired in patients undergoing CMF chemotherapy compared to patients not in chemotherapy; 23 of these hypotheses were confirmed. In addition, our study and other research suggest that other HRQL aspects may also be affected by chemotherapy. Thus, there is considerable evidence that patients in chemotherapy may experience effects on a wide spectrum of HRQL issues. Most other studies have assessed surprisingly few of the HRQL issues shown in our study to be impaired in patients receiving chemotherapy. Similarly, current review articles on HRQL effects of adjuvant chemotherapy mention only relatively few of these topics. Concerning HRQL after the treatment period, our main finding was that many symptoms and problems had declined or disappeared, but some persisted: anticipatory nausea, weight gain, endocrine effects (e.g., hot flushes/sweats, irregular bleedings/amenorrhea, vaginal dryness), disturbed sleep, and sexual dysfunction. These findings are in agreement with the literature. The staff study showed that experienced physicians and nurses did not expect many of the "scientifically well documented" consequences of chemotherapy. Taken together, our findings suggest that information to patients about chemotherapy should be more comprehensive than that which has been practised in most places. When compared against ovarian ablation, chemotherapy was associated with more impact on HRQL during the treatment period; only hot flushes/sweats were more pronounced in the ovarian ablation group. Thus, from an overall "HRQL perspective" ovarian ablation or suppression may be preferable. However, younger women may preserve their premenopausal status (including fertility) by having chemotherapy, and this may be an argument for chemotherapy or for temporary ovarian ablation via goserelin, rather than permanent ovarian ablation. Furthermore, while ovarian ablation/suppression may be preferable because of less impairment of HRQL, contemporary chemotherapeutic regimens may be more effective. These results indicate that for some patients, the HRQL data and results on treatment efficiency may be in conflict. There is no simple, universally correct solution to this dilemma. More research into patients' views and expectations to the health-care system in cases where medical decision-making involves complex trade-offs between treatment efficiency and HRQL issues is needed. Contrary to expectations, the analyses showed that fatigue and emotional function predicted the risk of recurrence and death independently of biological and clinical prognostic variables. In multivariate Cox regression analyses patients who were more fatigued or had poorer emotional function had a worse prognosis. These results are consistent with one small study, but are inconsistent with five similar studies in patients with primary breast cancer, which found no such associations. The reasons for these important differences are currently unknown. In conclusion, this study consisted of methodological and clinical investigations of HRQL in primary breast cancer patients. The initial questionnaire development resulted in a combination of questionnaires that was more comprehensive than in other similar studies. The results of the methodological studies generally supported the validity of the questionnaires but also gave important insights into potential scientific problems that are probably not restricted to the present study. These insights helped to prevent misinterpretations of the clinical data. The study provided the most detailed description of HRQL during and after breast cancer adjuvant chemotherapy to date, and compared results of chemotherapy against ovarian ablation. It also provided controversial results concerning the prognostic value of HRQL data. The combination of a large empirical study and several methodological sub-studies thus proved useful and gave new results.

Saturday, July 11, 2015

Death And Dying: Expanding Palliative Care

  JUL 10, 2015

Editor’s note: On Wednesday, Medicare, announced that it would reimburse doctors for end-of-life counseling. It’s part of an emerging conversation about end-of-life issues and the policy changes needed to give people more control over what happens to them in their final days. This three-part series of stories by KHI News Service, and a video produced in partnership with Kansas City public television station KCPT, is about that conversation and the role that experts at two regional institutions are playing in it. The first story in the series focuses on efforts to encourage end-of-life discussions and the thirdon the push to enact state laws allowing terminally ill patients to receive a doctor’s aid in dying.

Palliative care's dying with dignity

Published 6:51 pm, Tuesday, July 7, 2015

The recent conference in Colonie promoting assisted suicide points to the progress of the so-called "death with dignity" movement, which would reverse the ancient Hippocratic Oath to "do no harm" in favor of allowing physicians to become active agents in the deaths of patients.
The proponents of such a change in the law are no doubt motivated by a noble desire to prevent suffering. However, in so doing, they are seeking to sanitize the dying process in a dangerous way. What's more, they have latched on to the offensive argument that there is something inherently undignified about a natural death.
As a priest of 42 years, I can tell you that nothing can be further from the truth. In my priestly ministry, I have been at the deathbeds of more people than I can count. Usually, these individuals are elderly, but I have had the sad duty of consoling those burying children or young adults as well. No one wants to see a loved one die, but, without exception, the families to whom I have ministered have seen it not only as their duty but as their privilege to care for and see their loved ones through to the point where God called them home. Most of the deaths I have witnessed, including my own father's earlier this year, have been holy and peaceful.
Science has given us drugs that can be used to poison to death those who are suffering from the fear and depression that often accompanies terminal illness. But it has also given us something much more useful — palliative care, which enables medical personnel to control pain in remarkable ways, while at the same time preparing patients emotionally and spiritually for what is to come.
I appeal to our state legislators to reject legislation that promotes suicide for those considered as unuseful or a burden to society.

Thursday, July 2, 2015

 2015 Jun 26.[Epub ahead of print]

Physician Treatment Orders in Dutch Nursing Homes.



Physician treatment orders (PTOs) prevent burdensome unnecessary medical treatment of frail nursing home patients. The aim was to determine the prevalence of PTOs and time duration between nursing home admittance and PTO completion.


Population-based, retrospective cohort study.


Nursing homes across the Netherlands.


Digital medical records of patients who subsequently were submitted to 14 Dutch nursing homes across The Netherlands were studied between 2010 and 2013. The prevalence's of do-resuscitate, do-not-resuscitate, life-sustaining, and palliative care PTOs and the time intervals between nursing home admittance and documentation of PTOs were measured. Information regarding demographic patient characteristics, type of nursing home ward, and mention of a discussion of PTOs with the patient or caregivers was obtained.


Eighty-two percent of the nursing home patients received a PTO regarding resuscitation, life-sustaining, or palliative care treatment. Twenty-four percent of the patients received a do-resuscitation PTO, 55% received a do-not-resuscitate PTO, 44% a life-sustaining PTO, and 16% a palliative care PTO. The median duration between nursing home admittance and documentation of the first PTO was 1 day. Most nursing home patients had PTOs within 1 week after admittance.


A minority (18%) of Dutch nursing home patients has no documented PTOs during their nursing home stay, which could have negative effects on end-of-life care of nursing home residents.
Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.


Physician treatment order; advance care planning; long-term care facility; nursing home; palliative care; resuscitation
 2015 Jun 29. doi: 10.1002/pon.3887. [Epub ahead of print]

A tsunami of unmet needs: pancreatic and ampullary cancer patients' supportive care needs and use of community and allied health services.



People diagnosed with pancreatic cancer have the worst survival prognosis of any cancer. No previous research has documented the supportive care needs of this population. Our objective was to describe people's needs and use of support services and to examine whether these differed according to whether or not patients had undergone surgical resection.


Queensland pancreatic or ampullary cancer patients (n = 136, 54% of those eligible) completed a survey, which assessed 34 needs across five domains (Supportive Care Needs Survey-Short Form) and use of health services. Differences by resection were compared with Chi-squared tests.


Overall, 96% of participants reported having some needs. More than half reported moderate-to-high unmet physical (54%) or psychological (52%) needs, whereas health system/information (32%), patient care (21%) and sexuality needs (16%) were described less frequently. The three most frequently reported moderate-to-high needs included 'not being able to do things they used to do' (41%), 'concerns about the worries of those close' (37%) and 'uncertainty about the future' (30%). Patients with non-resectable disease reported greater individual information needs, but their needs were otherwise similar to patients with resectable disease. Self-reported use of support was low; only 35% accessed information, 28%, 18% and 15% consulted a dietician, complementary medicine practitioner or mental health practitioner, respectively. Palliative care access was greater (59% vs 27%) among those with non-resectable disease.


Very high levels of needs were reported by people with pancreatic or ampullary cancer. Future work needs to elucidate why uptake of appropriate supportive care is low and which services are required. Copyright © 2015 John Wiley & Sons, Ltd.
Copyright © 2015 John Wiley & Sons, Ltd.
 2014 Nov;20(11):542-8. doi: 10.12968/ijpn.2014.20.11.542.

Perspectives of an international education initiative in children's palliative care.


Education is viewed as central to improving future palliative care for children and families across all countries. International education initiatives will ensure practitioners are aware of global health issues and can provide culturally sensitive care. Creative and innovative means of meeting such directives are required to achieve meaningful student learning. 
This paper focuses on one innovation, a children's palliative care workshop using case studies as a teaching method, with nursing students from the USA and nursing and midwifery students from the UK. Key learning points arising from student evaluation were recorded under three main themes, these were: differences across countries, similarities across countries, and making learning fun and memorable. 

Findings indicated that this joint learning activity was viewed positively by all students and has enabled them to learn with and from each other, potentially impacting on their future practice.