Abstract
Background
Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the aim of prolonging the life of a patient, improving their quality of life, or both. This is an updated version of the original Cochrane review published in Issue 2, 2008, and updated in February 2011.
Objectives
To determine the effect of medically assisted hydration in palliative care patients on their quality and length of life.
Search methods
We identified studies by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, Caresearch, Dissertation abstracts, SCIENCE CITATION INDEX and the reference lists of all eligible studies, key textbooks and previous systematic reviews. The date of the latest search conducted on CENTRAL, MEDLINE and EMBASE was March 2014.
Selection criteria
All relevant randomised controlled trials (RCTs) or prospective controlled studies of medically assisted hydration in palliative care patients.
Data collection and analysis
We identified six relevant studies for this update. These included three RCTs (222 participants), and three prospective controlled trials (360 participants). Two review authors independently assessed the studies for quality and validity. The small number of studies and the heterogeneity of the data meant that a quantitative analysis was not possible, so we included a description of the main findings.
Main results
One study found that sedation and myoclonus (involuntary contractions of muscles) scores were improved more in the intervention group. Another study found that dehydration was significantly higher in the non‐hydration group, but that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group. The other four studies (including the three RCTs) did not show significant differences in outcomes between the two groups. The only study that had survival as an outcome found no difference in survival between the hydration and control arms.
Authors' conclusions
Since the last version of this review, we found one new study. The studies published do not show a significant benefit in the use of medically assisted hydration in palliative care patients; however, there are insufficient good‐quality studies to inform definitive recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.
Plain language summary
Medically assisted hydration to assist palliative care patients
Background
It is common for palliative care patients to have reduced fluid intake during their illness. Management of this condition includes discussion with the patient, family and staff involved, and may include the provision of fluids with medical assistance. This can be performed using a small plastic tube inserted into a vein or under the skin, or via a tube inserted into the stomach. It is unknown whether this treatment helps people to feel better or live longer.
Study characteristics
We searched the international literature for randomised controlled trials looking at the effects of medically assisted hydration in adults receiving palliative care. Randomised controlled trials allocate patients to one of two or more treatment groups in a random manner and provide the most accurate information on the best treatment. We conducted the searches in April 2013 and March 2014.
Key results and quality of evidence
We found only six studies looking at this issue. The studies did not show a significant benefit in the use of medically assisted hydration in palliative care patients; however, there are insufficient good‐quality studies to make any definitive recommendations. . As a result, it is not possible to define the benefits and harms of this treatment clearly.
Background
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 2, 2008) on "Medically assisted hydration for adult palliative care patients" (Good 2008).
Description of the condition
Many palliative care patients have a reduced oral intake during their illness. The cause of this varies, but may be due partly to a physical obstruction, anorexia/cachexia syndrome, generalised weakness, bowel obstruction, nausea, decreased level of consciousness, loss of desire to drink or no specific cause may be identified. The most common time for this decreased oral intake is during the terminal phase, when the patient becomes less conscious and, therefore, less able to receive fluids orally (Morita 1998).
Description of the intervention
Management of this condition includes discussion with the patient, family and staff involved, and either no medical intervention (but continued attention to treating any symptomatic problems, including good mouth care) or the provision of hydration with medical assistance. Medically assisted hydration is usually performed via the intravenous or subcutaneous routes (parenteral), but can also use the gastrointestinal system (enteral). There is great variation in practice with regards to hydration. For example, Lanuke 2003 found that the rate of provision of medically assisted hydration differed greatly across Canada (range 0% to 100%).
How the intervention might work
The aim of medically assisted hydration can be to prolong the length of life of a patient, improve their quality of life (QoL), or both. These benefits may come via the reversal of the physiological factors associated with the patient's decline. Balanced against these potential benefits are adverse events that can be associated with any intervention (infection, bleeding, pain, etc.) (Bozzetti 1996).
Why it is important to do this review
There is controversy about the ethical aspects of medically assisted hydration (Casarett 2005). The first ethical controversy centres on whether medically assisted hydration is a medical intervention or a basic provision of comfort. Second, there is controversy as to how and by whom decisions should be made with regards to medically assisted hydration in patients who no longer have the capacity to make decisions for themselves. This review will concentrate on assessing the benefit of provision of hydration with medical assistance versus the harm caused by such intervention in palliative care patients. It is only with this information that clinicians and patients can make informed decisions about whether this type of intervention is beneficial or harmful to an individual patient. There is a separate review considering medically assisted nutrition for palliative care patients (Good 2014).
Objectives
To determine the effect of medically assisted hydration in palliative care patients on their QoL and length of life.
Methods
Criteria for considering studies for this review
Types of studies
All relevant randomised controlled trials (RCTs) or prospective controlled studies that fulfilled the inclusion criteria.
Types of participants
Participants included:
palliative care participants who received medically assisted hydration;
patients receiving palliative care (WHO 2005);
(but were not limited to) incurable cancer, dementia, neurodegenerative diseases (e.g. motor neuron disease), human immunodeficiency virus, chronic airways limitation and chronic heart failure;
whose prognosis was limited and the focus of care was QoL (Doyle 2004); and
adults aged 18 years and above, both male and female and in any setting such as home, hospice or hospital.
We did not limit included participants to those in the terminal phase of their illness. We excluded participants who were having medically assisted hydration as part of a perioperative, chemotherapy or radiotherapy regimen, or because of chemotherapy or radiotherapy adverse effects.
Types of interventions
Medically assisted administration of fluids
Medically assisted hydration ‐ administration of non‐nutritional fluids, administered via the subcutaneous tissue, venous system or enterally (nasogastric tube, jejunostomy, gastrostomy).
Comparisons
Placebo.
No intervention.
Usual treatment or supportive care.
Types of outcome measures
Primary outcomes
QoL on any measure (including symptom assessment scales).
Secondary outcomes
Survival.
Adverse events.
Search methods for identification of studies
Electronic searches
We searched the following electronic databases using a search strategy developed for MEDLINE via Ovid, but were modified appropriately for each database. See Appendix 1 for the search strategies.
Cochrane Central Register of Controlled Trials (CENTRAL) (searched up to Issue 2, 2014).
MEDLINE (Ovid) (1966 to 25/03/2014).
EMBASE (Ovid) (1980 to 25/03/2014).
SCIENCE CITATION INDEX (ISI Web of Science) (1900 to March 2014).
CINAHL (EBSCO) (1982 to March 2014).
CANCERLIT (up to February 2008).
Caresearch ‐ database listing conference proceedings and grey literature (up to February 2008).
Dissertation abstracts (up to February 2008).
Searching other resources
Reference lists
We searched the reference lists of all eligible studies, key textbooks and previous systematic reviews for additional studies.
Language
The search attempted to identify all relevant studies irrespective of language. We found no non‐English papers.
Data collection and analysis
Selection of studies
The original search was performed in October 2006, and repeated in February 2008. A further search was performed in November 2010 for the first update. The original review included five studies, with no new studies added for the first update. We performed subsequent searches in April 2013 and March 2014 for the update of this review (see Figure 1). From this search, we reviewed the titles and abstracts and retrieved publications of eight studies in full. After review of these articles, seven did not meet the inclusion criteria, leaving one new study for inclusion (in addition to the five studies from original review and update).
1.
Study flow diagram.
Data extraction and management
Data extraction
We obtained the following information for each study:
study methods (study design, allocation, blinding, setting, inclusion criteria);
participants (sample size, exclusions/inclusions, number, disease, duration of study, withdrawals and drop‐outs, site ‐ e.g. hospital, hospice, home);
intervention (type, route of delivery, control used);
outcome (QoL, symptom measures, survival, time from death intervention was initiated); and
adverse effects.
All review authors extracted this information independently, and agreed the final data by consensus.
Data analysis
We planned to pool results had there been sufficient data and homogeneity between studies. However, we identified only three RCTs, and only a small number of participants were recruited to these studies. The heterogeneity of the data meant that a quantitative analysis was not possible. A description of the main findings from the studies is presented in the Results section.
Assessment of risk of bias in included studies
Quality
We assessed the methodological quality of the six studies.
Assessment of risk of bias in included studies
For this update, we continued to assess quality using the Oxford Quality Scale (Jadad 1996), which allocates points for randomisation, blinding and the recording of study withdrawals. This scale uses the following questions to rate the likelihood of bias (the higher the score the less likelihood of bias, scale of zero to five).
Was the study described as randomised (one = yes; zero = no)?
Was the study described as double blind (one = yes; zero = no)?
Was there a description of withdrawals and drop‐outs (one = yes; zero = no)?
Was the method of randomisation well described and appropriate (one = yes; zero = no)?
Was the method of double‐blinding well described and appropriate (one = yes; zero = no)?
Deduct one point each if methods for randomisation and blinding were inappropriate.
Scoring system: maximum score = five; minimum score = zero.
The maximum possible score (indicating a trial of high methodological quality) is five.
Three studies were prospective controlled trials and their methodology was assessed using a scale devised by Rinck et al. (Rinck 1997).
Quality criteria ‐ accrual of the study population.
Homogeneity and participant characteristics.
Randomisation.
Attrition and sample size.
Interventions.
Outcome measurement.
Presentation of results.
Score one point if criteria fully applied. Score 0.5 point if criteria was not fully applied. Score zero if criteria (mostly) not applied. Scoring system: maximum score = seven, minimum score = zero.
For this update, we also used the Cochrane 'Risk of bias' tool. We completed a 'Risk of bias' table for each included study, using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
We assessed the following for each study:
Random sequence generation (checking for selection bias).
Allocation concealment (checking for selection bias).
Blinding of participants and personnel (checking for performance bias).
Blinding of outcome assessment (checking for detection bias).
Incomplete outcome data (checking for attrition bias).
Selective reporting (checking for reporting bias).
Size of study (checking for possible biases confounded by small size). We assessed studies as being at low risk of bias (≥ 200 participants per treatment arm); unclear risk of bias (50 to 199 participants per treatment arm); high risk of bias (< 50 participants per treatment arm).
The results for each included study are reported in the Characteristics of included studies table.
Results
Description of studies
The searches for this update were run in April 2013 and March 2014, which identified one new RCT (Bruera 2013, 129 participants) (see Figure 1 for details of the study selection process). In addition to this new study were the original five studies in which two were RCTs (Bruera 2005, 51 participants; Cerchietti 2000, 42 participants), and three were prospective controlled trials (Morita 2005, 226 participants; Waller 1994, 68 participants; Viola 1997, 66 participants). For the original search, seven studies appeared to meet the inclusion criteria (Bruera 2005; Cerchietti 2000; Morita 2002; Morita 2005; Morita 2006; Waller 1994; Viola 1997). On further review, two studies were excluded (Morita 2002; Morita 2006). One study was excluded because there were no comparisons between the groups with regards to hydration (Morita 2002). The second study was excluded because there was no comparison between the symptoms of the hydrated and non‐hydrated groups (Morita 2006).
Study design
Three studies had an RCT design (Bruera 2005; Bruera 2013; Cerchietti 2000). The study intervention of these was for two days (Bruera 2005; Cerchietti 2000) or "until the patient was unresponsive, developed progressive coma, or died" (Bruera 2013). The other three studies had a prospective controlled trial design (Morita 2005; Waller 1994; Viola 1997). The study conducted in Japan by Morita 2005 had a study duration of three weeks, while the study by Waller 1994 was from admission to a hospice until death and Viola 1997 was from enrolment in the study until death, discharge or no longer having a fluid deficit.
Study population
All of the studies included only participants with advanced cancer. Four studies only included participants in whom it was thought the participants were dehydrated (Bruera 2005; Bruera 2013; Cerchietti 2000; Viola 1997).
Intervention
All of the studies aimed to administer at least 1000 mL of fluid per day to the intervention group. The route of this varied between intravenous and subcutaneous.
Outcomes
The outcomes measured in all the studies were very different.
Waller 1994 only considered the state of consciousness.
Bruera 2005 had a main outcome measure as the global assessment of the overall benefit of hydration to the participant, as determined by the physician and participant on day two. This was supplemented by a number of secondary outcome measures. These included symptom assessment scales used for sedation, fatigue, hallucinations, myoclonus, symptoms totalled together and the Mini Mental Status Examination (MMSE). These symptoms were scored on a numerical rating of zero to 10 scale, with a decrease of one point indicating an improvement (this was defined by the authors and it is unclear whether this is a statistical or clinical improvement).
The RCT by Bruera 2013 had the primary outcome as the change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations) between day four and baseline. Secondary outcome measures included delirium (Memorial Delirium Assessment Scale (MDAS), Richmond Agitation Sedation Scale (RASS) Nursing Delirium Screening Scale (NuDESC)), change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations) between day seven and baseline, global symptom evaluation, QoL using Functional Assessment of Chronic Illness Therapy ‐ Fatigue (FACIT‐F) and Functional Assessment of Chronic Illness Therapy ‐ General (FACIT‐G), hydration status using a dehydration assessment scale and survival.
Cerchietti 2000 primarily studied the symptoms of thirst, chronic nausea, delirium and changes in MMSE. Secondary outcome measures included anguish and mood.
The observational study of Morita 2005 examined dehydration, fluid retention (ascites, bronchial secretions, peripheral oedema), hyperactive delirium, myoclonus, bedsores, agitation and communication capacity.
Viola 1997 studied the prevalence of multiple physical symptoms and cognition.
Two RCTS examined adverse effects of medically assisted hydration including local adverse effects (discomfort, pain, infection, oedema, erythema, bleeding at the puncture site) and interruption of hydration due to adverse effects (oedema, increase in respiratory secretions, congestive heart failure) (Bruera 2005; Cerchietti 2000).
Risk of bias in included studies
All review authors assessed the included studies using two different quality scales. We assessed the three RCTs using the Oxford Quality Scale (Jadad 1996). Two of the RCTs scored five out of five on this scale, as they were well‐designed and well‐performed studies (Bruera 2005; Bruera 2013). In particular, the methods of randomisation and blinding were well described and appropriate. However, the third RCT scored only two out of five, as neither the method of randomisation nor whether any blinding was performed were described (Cerchietti 2000).
The other three studies were prospective controlled trials and we assessed their quality using the Rinck scale (Rinck 1997). One of the studies, Morita 2005, scored 4.5 out of a maximum of seven on this scale. Its strengths were that consecutive participants were asked to be enrolled and a good description of baseline characteristics and follow‐up was given. However, allocation was via physician preference, thus introducing an element of bias, and there was no blinding of allocation to scoring of outcomes. The aim of the allocation according to physician preference was to try to mimic real world decision making. The study by Waller 1994 was subject to many methodological problems. There was inadequate inclusion and recruitment strategy, a poorly defined control group, no baseline data presented for groups, and the length of time and composition of intravenous fluids was not included. This paper scored 1.5 out of seven on the Rinck scale. The third prospective study scored four out of seven on the Rinck scale (Viola 1997). This study was well designed, but the major shortcoming was in recruitment and performance of the study. Recruitment was performed at two different centres, and the two groups at baseline had many differences including type of cancers and symptom assessment scores. This meant that we were unable to make a true comparison between the group receiving medically assisted hydration and the control group receiving no medically assisted hydration in any of the outcome measures.
For this update, we incorporated the Cochrane 'Risk of bias' tool. The findings are listed in the 'Risk of bias' table in the Characteristics of included studies table. The overall findings are presented in the 'Risk of bias' graph (Figure 2) and the 'Risk of bias' summary (Figure 3). The two RCTs by Bruera et al. had a low risk of bias (except for size of study) (Bruera 2005; Bruera 2013), while all the others had high or unclear risk across all the categories.
2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Effects of interventions
Effectiveness
One study found that sedation and myoclonus were more greatly improved in the intervention group (Bruera 2005). In addition, if the total scores for the four target symptoms (sedation, fatigue, hallucinations, myoclonus) were taken as a whole, there was more improvement in the intervention group. The secondary outcome measure used in the Bruera 2005 study (proportion of participants perceived to have some benefit was 50% or greater) was significant in the hydration group in the view of the physicians but not the participant's viewpoint. In another study (Cerchietti 2000), it was stated that "control of chronic nausea after 24 hours was significantly better in the group receiving hydration". However, the results were never tabulated, but rather presented in a graphical form, and this actually showed the two groups almost equal after 24 hours, and the non‐hydration group improving more than the hydration group in terms of lowering the visual analogue score for chronic nausea. One study found that night‐time delirium was worse in the control group compared with the hydration group at day four, (but not day seven) as measured by NuDESC (Bruera 2013). There were no significant differences found in all the other outcomes examined at in five other studies in terms of effectiveness of medically assisted hydration (Bruera 2005; Bruera 2013; Cerchietti 2000; Morita 2005; Waller 1994). The fifth study only provided descriptive statistics, and so a comparison between the groups was not possible (Viola 1997). In the one study that had survival as an outcome measure, there was no difference between the hydration and control groups (Bruera 2013).
Adverse events
In terms of local adverse reactions, Bruera 2005 reported no differences between the groups, but Cerchietti 2000 found there was one participant with erythema and pain at the puncture site in the intervention group. Morita 2005 found that dehydration was significantly higher in the non‐hydration group, and that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group.
Discussion
The objective of this systematic review was to determine the effect of medically assisted hydration in palliative care patients on their QoL and length of life. Extensive searching of the literature produced only six studies suitable for inclusion. This included three RCTs. Two of these were of high methodological quality, but were unable to recruit a sufficient number of participants to adequately power the studies (Bruera 2005; Bruera 2013), while the other had methodological flaws in design and reporting of results (Cerchietti 2000). One of these studies had survival as an outcome and found no difference between the hydration and control arm (Bruera 2013). Of the three prospective controlled studies, one was of reasonable quality (Morita 2005), while another had methodological shortcomings in design and reporting (Waller 1994). The third prospectively controlled trial had a good methodological basis, but unfortunately, the two groups recruited had many differences at baseline (Viola 1997). There was also no statistical analysis of the results to determine if any differences were significant. The participants included in these studies represent a 'narrow' palliative care population in that they all have cancer that is defined as 'advanced' or 'terminal'. It is questionable whether the results of these studies would be generalisable to a wider palliative care population, especially people who do not have cancer.
One study found that sedation and myoclonus (involuntary contractions of muscles) scores were improved more in the intervention group. Another study found that hydration may also cause some adverse effects in terms of fluid retention (in particular pleural effusion, peripheral oedema and ascites). However, these results must be taken within the context of low participant numbers and methodological difficulties in the studies.
There has been much debate and varying views about the provision of medically assisted hydration to palliative care patients (Ashby 1995; Craig 1994;Dev 2012; Raijmakers 2011). This review shows that there have been very few high‐quality studies examining the symptom benefits, and adverse effects of such an intervention.
Authors' conclusions
Implications for practice.
Since the last version of this review, we found one new study. The studies published show no significant benefit in the use of medically assisted hydration in palliative care patients; however, there are insufficient good quality studies to inform definitive recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.
There are a few good‐quality studies that examine the benefits and harms of the use of medically assisted hydration in this population. Two randomised controlled trials (RCTs) in this review had a short duration of hydration (two days) to assess effects, and no information on the effect hydration may have on survival. The other RCT was of longer duration, and found little difference in outcomes between the hydration and control groups. It also found no difference in survival between the two groups. The results from one included study suggest that there may be some benefit in terms of improvement in sedation and myoclonus, but another study showed that there may be some harm in terms of worsening of fluid retention symptoms (pleural effusion, peripheral oedema and ascites) and these results need to be taken in the context of low participant numbers, limited palliative care settings and narrow palliative care patient population groups. Clinicians will need to make a decision based on the perceived benefits and harms of medically assisted hydration in individual patient circumstances, without the benefit of high‐quality evidence to guide them.
Implications for research.
Study design
High‐quality studies in the palliative care population have proven very difficult to perform successfully. The difficulty of research in a vulnerable population such as palliative care patients has been discussed in the literature. These difficulties start with consent, are followed by recruitment, elimination of confounders and end with retention of participants throughout a study period (Rinck 1997). There have been some innovative suggestions about how to overcome the issue of consent (Rees 2003), and some studies have used this methodology with success (Breitbart 2002). Other studies have shown that large numbers are not always needed to show a benefit (Abernethy 2003), but the question of safety is difficult to answer due to the small numbers of participants commonly being found in palliative care studies. This has been illustrated by the fact that there were only two RCTs of a high quality in this review. Despite being methodologically sound, the results were limited by lack of recruitment. Perhaps of more interest was that the issue of medically assisted hydration in palliative care patients causes such divergent views, yet there are so few studies to guide clinical practice properly. As well as examining further RCTs in this area, the evidence base will be improved with at least more prospective controlled trials.
Participant groups
The studies in this review had narrowly defined patient populations. Palliative care is performed in hospitals, inpatient palliative care units and in the community. Studies need to be performed in all these areas to allow external validity to different palliative care populations. It would also be helpful to define at what stage of their illness participants are being given medically assisted hydration. The reasons and aims of hydration in the last few days/weeks of life may be very different to those participants with a longer prognosis. An agreed diagnostic criteria for hydration status is essential for future trials, both to assess at entry and to assess as an outcome. In addition, all the participants in the included studies had advanced cancer, and it is important to examine medically assisted hydration in non‐cancer populations. The prospective prediction of prognosis is difficult, and it may be better to stratify participants according to their performance status.
Interventions
Medically assisted hydration can be given by many different routes. The studies included in this review used either the subcutaneous or intravenous route. We found no studies that used the enteral route for hydration. Further studies are needed to determine the optimum route and dose.
Outcomes
It is important that clinically relevant outcomes are clearly defined and are the most clinically useful. In this patient population, this should include symptoms (such as sedation, fatigue, hallucinations and myoclonus) as well as diagnoses such as delirium. Despite much controversy about the effect medically assisted hydration may have on length of life, it was only included as an outcome in one study in this review. Future studies should include the survival of participants as an outcome. It is equally important that adverse events are well defined so that the risk of treatment can be balanced against any benefits.
What's new
| Date | Event | Description |
|---|---|---|
| 8 May 2015 | Review declared as stable | This review will be assessed for further updating in 2019. |
History
Protocol first published: Issue 4, 2006 Review first published: Issue 2, 2008
| Date | Event | Description |
|---|---|---|
| 16 April 2014 | New citation required and conclusions have changed | The search for this review was re‐run in April 2013 and March 2014. No new studies were found. Minor change to conclusions. We recommend that readers of the original review read this latest version. |
| 9 January 2014 | New search has been performed | We added a PRISMA flowchart to document the study selection process and added risk of bias tables. |
| 14 February 2011 | New search has been performed | The search for this review was re‐run in February 2011. No new studies were identified to be included in this review. |
| 6 October 2010 | Amended | Contact details updated. |
| 6 August 2008 | Amended | Converted to new review format. |
Acknowledgements
We wish to thank the Cochrane Pain, Palliative and Supportive Care Review Group for ongoing support in updating this review.
John Cavenagh, Mark Mather and Peter Ravenscroft were authors on the original review but did not contribute to this update.
Appendices
Appendix 1. Search strategies for 2014 update
CENTRAL (The Cochrane Library)
#1 MeSH descriptor: [Palliative Care] explode all trees
#2 palliat*:it,ab,kw (Word variations have been searched)
#3 MeSH descriptor: [Terminally Ill] this term only
#4 MeSH descriptor: [Terminal Care] explode all trees
#5 (terminal* near/6 care*):it,ab,kw (Word variations have been searched)
#6 ((terminal* near/6 ill*) or terminal‐stage* or dying or (close near/6 death)):it,ab,kw (Word variations have been searched)
#7 (terminal* near/6 disease*):it,ab,kw (Word variations have been searched)
#8 (end near/6 life):it,ab,kw (Word variations have been searched)
#9 hospice*:it,ab,kw (Word variations have been searched)
#10 ("end‐stage disease*" or "end stage disease* or end‐stage illness" or "end stage"):it,ab,kw (Word variations have been searched)
#11 "advanced disease*":it,ab,kw (Word variations have been searched)
#12 ("incurable illness*" or "incurable disease*"):it,ab,kw (Word variations have been searched)
#13 ("advanced directive*" or "living will*" or "do‐not‐resuscitate order*"):it,ab,kw (Word variations have been searched)
#14 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13
#15 MeSH descriptor: [Fluid Therapy] this term only
#16 MeSH descriptor: [Dehydration] this term only
#17 (hydrat* or dehydrat* or rehydrat* or (fluid* near/6 therap*) or (fluid* near/6 balance*) or (fluid* near/6 manag*) or hypodermoclysis):it,ab,kw (Word variations have been searched)
#18 #15 or #16 or #17
MEDLINE (Ovid)
1 exp Palliative Care/
2 palliat*.tw.
3 Terminally Ill/
4 Terminal Care/
5 (terminal* adj6 care*).tw.
6 ((terminal* adj6 ill*) or terminal‐stage* or dying or (close adj6 death)).tw.
7 (terminal* adj6 disease*).tw.
8 (end adj6 life).tw.
9 hospice*.tw.
10 ("end‐stage disease*" or "end stage disease* or end‐stage illness" or "end stage").tw.
11 "advanced disease*".tw.
12 ("incurable illness*" or "incurable disease*").tw.
13 ("advanced directive*" or "living will*" or "do‐not‐resuscitate order* ").tw.
14 or/1‐13
15 Fluid Therapy/
16 Dehydration/ (9949)
17 (hydrat* or dehydrat* or rehydrat* or (fluid* adj6 therap*) or (fluid* adj6 balance*) or (fluid* adj6 manag*) or hypodermoclysis).tw.
18 15 or 16 or 17
19 14 and 18
20 (2010* or 2011* or 2012* or 2013* or 2014*).ed.
21 19 and 20
EMBASE (Ovid)
1 exp Palliative Care/
2 palliat*.tw.
3 Terminally Ill/
4 Terminal Care/
5 (terminal* adj6 care*).tw.
6 ((terminal* adj6 ill*) or terminal‐stage* or dying or (close adj6 death)).tw.
7 (terminal* adj6 disease*).tw.
8 (end adj6 life).tw.
9 hospice*.tw.
10 ("end‐stage disease*" or "end stage disease* or end‐stage illness" or "end stage").tw.
11 "advanced disease*".tw.
12 ("incurable illness*" or "incurable disease*").tw.
13 ("advanced directive*" or "living will*" or "do‐not‐resuscitate order* ").tw.
14 or/1‐13
15 Fluid Therapy/
16 Dehydration/
17 (hydrat* or dehydrat* or rehydrat* or (fluid* adj6 therap*) or (fluid* adj6 balance*) or (fluid* adj6 manag*) or hypodermoclysis).tw.
18 15 or 16 or 17
19 14 and 18
20 (2010* or 2011* or 2012* or 2013* or 2014*).dd.
21 19 and 20
Science Citation Index (ISI Web of Science)
# 13 295 #12 AND #11
# 12 53,258 Topic=((hydrat* or dehydrat* or rehydrat* or (fluid* near/6 therap*) or (fluid* near/6 balance* ) or (fluid* near/6 manag* ) or hypodermoclysis))
# 11 37,433 #10 OR #9 OR #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
# 10 386 Topic=(("advanced directive*" or "living will*" or "do‐not‐resuscitate order*"))
# 9 412 Topic=(("incurable illness*" or "incurable disease*"))
# 8 3,316 Topic=("advanced disease*")
# 7 12,963 Topic=(("end‐stage disease*" or "end stage disease* or end‐stage illness" or "end stage"))
# 6 2,135 Topic=(hospice*)
# 5 6,392 Topic=((end near/3 life))
# 4 1,176 Topic=((terminal* near/6 disease*))
# 3 1,527 Topic=((terminal* near/6 ill*))
# 2 906 Topic=((terminal* near/6 care*))
# 1 14,889 Topic=(palliat*)
CINAHL (EBSCO)
S23 S14 AND S22
S22 S15 OR S16 OR S17 OR S18 OR S19 OR S21
S21 (fluid* N6 manag* )
S20 (fluid* N6 balance* )
S19 (fluid* N6 therap*)
S18 hypodermoclysis
S17 (hydrat* or dehydrat* or rehydrat*)
S16 (MH "Dehydration")
S15 (MH "Fluid Therapy")
S14 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13
S13 ("advanced directive*" or "living will*" or "do‐not‐resuscitate order*")
S12 ("incurable illness*" or "incurable disease*")
S11 "advanced disease*"
S10 ("end‐stage disease*" or "end stage disease* or end‐stage illness" or "end stage")
S9 hospice*
S8 (end n3 life)
S7 (terminal* N6 disease*)
S6 (terminal* N6 ill*)
S5 (terminal* N6 care*)
S4 (MH "Terminal Care+")
S3 (MH "Terminally Ill Patients+")
S2 palliat*
S1 (MH "Palliative Care")
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Bruera 2005.
| Methods | Randomised, controlled, double‐blind, multicentre trial Method of randomisation: truly random Study duration: 2 days | |
| Participants | Participants with a diagnosis of advanced cancer, defined as locally recurrent or metastatic, with no further treatment planned
An oral intake < 1000 mL/day, as determined by clinical assessment; and evidence of mild‐to‐moderate dehydration, exhibited by decreased turgor in the subclavicular region lasting > 2 seconds
Participants had to have ≥ 1 of the following findings: dry mouth; thirst; decreased volume of urine output, as reported by the patient; a darker colour of urine than usual, in the absence of reasons for jaundice or haematuria; and laboratory values consistent with dehydration, such as an elevated blood urea nitrogen to creatinine ratio of more than 20:1, when this value was obtained within 24 hours of admission to the study
Participants had to be > 16 years, able to understand and give consent for participation in the study, and able to tolerate parenteral treatment and the application of a subcutaneous or IV cannula Sample size: 74 (13 were not eligible, 10 refused) 51 recruited |
|
| Interventions | 51 patients were randomised to 1 of 2 groups
Route of administration: IV if IV access available (12 patients); subcutaneous if no IV access (37 patients) |
|
| Outcomes | Primary outcome was the global assessment of the overall benefit of hydration to the participant, as determined by the physician and patient on day 2 ‐ no statistically significant difference between groups
Secondary method of analysis was to test the 2 groups separately to determine whether the proportion of patients perceived to have some benefit was 50% or > 50% ‐ intervention group ‐ P value = 0.0035, placebo group ‐ P value = 0.20
Target symptoms ‐ numerical rating scale 0‐10, with a decrease of 1 point seen as an improvement
Sedation: more improvement in intervention group (P value = 0.005)
Fatigue: no difference between groups
Hallucinations: no difference between groups
Myoclonus: more improvement in intervention group (P value = 0.035)
Symptoms totalled together: more improvement in intervention group (P value = 0.06)
MMSE: no difference Adverse effects: pain at injection site, injection site swelling: no differences between groups |
|
| Notes | Oxford Quality Scale score: 5
Some differences in performance status at randomisation, with intervention group have more participants in performance status 0, I and II Study was underpowered, as recruitment was less than expected |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Random numbers" |
| Allocation concealment (selection bias) | Low risk | "Sealed envelopes" |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Double blind" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Blinding of outcome assessor |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All participants accounted for |
| Selective reporting (reporting bias) | Low risk | No problems detected |
| Size of Study (possible biases confounded by small size) | High risk | < 50 participants per treatment arm |
Bruera 2013.
| Methods | Randomised, placebo‐controlled, double‐blind, multicentre study Method of randomisation: computer‐generated simple randomisation scheme |
|
| Participants | Advanced cancer (i.e. locally recurrent or metastatic disease) who were:
Sample size: 905 patients assessed for eligibility Excluded: 776 Included: 129 |
|
| Interventions | 129 patients were randomised to 1 of 2 groups
|
|
| Outcomes | Primary outcome:
Secondary outcomes:
|
|
| Notes | Oxford Quality Scale score: 5 Underpowered ‐ powered for 150 patients but recruitment stopped at 129 due to funding limitations |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Computer‐generated simple randomization scheme" |
| Allocation concealment (selection bias) | Low risk | "Pharmacist randomly assigned patients" |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Identical backpacks" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Research nurse conducting the study assessments was blinded to study intervention and randomisation sequence |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All participants accounted for |
| Selective reporting (reporting bias) | Low risk | No problems detected |
| Size of Study (possible biases confounded by small size) | Unclear risk | 50‐199 participants per treatment arm |
Cerchietti 2000.
| Methods | Randomised, comparative prospective, single‐centre trial Method of randomisation: unclear Blinding status: unclear Study duration: 48 hours | |
| Participants | Terminal stage advanced cancer patients. ≥ 1 of the following symptoms: thirst; chronic nausea or delirium; dehydration diagnosed on physical examination, with or without renal failure; and inability to maintain an adequate water intake (< 50 mL/day fluid) Sample size: 50 Exclusions: 4 uncontrolled symptoms (pain in 2 of the participants, severe dyspnoea in 2), 1 bowel obstruction syndrome requiring surgery, 3 severe constipation |
|
| Interventions | 42 patients were randomised to 1 of 2 groups
|
|
| Outcomes | Primary outcomes (VAS):
The results were not tabulated, and some graphs were given. The authors stated, "that 1000 ml/day subcutaneous hydration does not improve control of the assessed symptoms when added to the general and pharmacological treatment in patients with end‐stage cancer. However, control of chronic nausea after 24 hours was significantly better in the group receiving hydration" However, the graph of this actually shows the 2 groups both improving and the non‐hydration group improving more in terms of the VAS Secondary outcomes:
|
|
| Notes | Oxford Quality Scale score: 2 Median survival: about 4 days in both groups | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | States "randomly assigned", but method not adequately described |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | No blinding described |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | No blinding described |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Method not described |
| Selective reporting (reporting bias) | Unclear risk | Insufficient information |
| Size of Study (possible biases confounded by small size) | High risk | < 50 participants per treatment arm |
Morita 2005.
| Methods | Prospective, observational, multicentre study Method of randomisation: none Study duration: 3 weeks | |
| Participants | Age > 20 years; life expectancy estimated by a physician to be < 3 months; and incurable malignancy of abdominal origin (excluding hepatic malignancies)
Sample size: 498 participants who met the inclusion criteria were consecutively recruited for this study
Excluded: 272 participants for the following reasons: 200 death within 3 weeks of initial assessment, 35 survival beyond the observation period, 17 medical complications, 15 prior communication difficulty, 5 discharged Included: 226 patients (49 from oncology units and 177 from palliative/home‐care settings) |
|
| Interventions | 226 patients were randomised to 1 of 2 groups
The mean hydration volume in the hydration group was 838‐1405 mL/day during the last 3 weeks, and the median hydration volume in the non‐hydration group was 200 mL/day at all 3 observation points Form of hydration was unclear, but a previous paper described it as IV |
|
| Outcomes |
|
|
| Notes | Rinck score: 4.5 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Not randomised |
| Allocation concealment (selection bias) | High risk | Not randomised |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Not blinded |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Method not described |
| Selective reporting (reporting bias) | Unclear risk | Insufficient information |
| Size of Study (possible biases confounded by small size) | Unclear risk | 50‐199 participants per treatment arm |
Viola 1997.
| Methods | Prospective, comparative study
Multicentre study ‐ Edmonton (hydration group) and Ottawa (no hydration group)
Method of randomisation: none Study duration: enrolment until death, no longer having a fluid deficit or discharge from palliative care unit |
|
| Participants | Advanced cancer Phase I: inpatients of either Edmonton or Ottawa palliative care units with advanced cancer, not aphasic, MMSE > 24 and subjectively competent (as judged by physician), able to understand English (Edmonton) or English or French (Ottawa) Participant at risk of developing a fluid deficit or on admission already having a fluid deficit:
Exclusions: receiving enteral tube feedings, acute renal failure, pulmonary oedema or bleeding disorder, aphasic, MMSE < 24 Sample size: 288 Excluded: 165 (164 with cognitive deficit, 1 with bleeding disorder) Consent sought: 123 Consented Phase I: 94 Considered for Phase II: 70 Entered Phase II: 68 (2 excluded as no data collected) leaving 66 participants |
|
| Interventions | 66 patients were randomised to 1 of 2 groups
|
|
| Outcomes | VAS: 12 symptoms ‐ pain, activity, nausea, depression, anxiety, drowsiness, appetite, sense of well‐being, dyspnoea, weakness, thirst and dry mouth Assessed by participants or staff depending on ability of participants
Bowel movements
Vomiting
Pressure ulcers
Peripheral oedema
Myoclonus
Level of consciousness
Delirium Rating Scale
MMSE
Oral mucosal assessment Time spent in Phase II and survival from enrolment in Phase II. The demographics of the groups differed at study entry and there were also many differences in the outcome measures at baseline. Results were only reported as frequency in each group, and there was no statistical analysis performed to determine if there was any significant differences between the groups on any of the measured outcomes |
|
| Notes | Rinck score 4 Well‐designed study, but the major flaw was that the groups were not matched at study entry | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | No randomisation |
| Allocation concealment (selection bias) | High risk | Groups differed at study entry |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | No blinding |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | No blinding |
| Incomplete outcome data (attrition bias) All outcomes | High risk | As treated analysis |
| Selective reporting (reporting bias) | Unclear risk | Not described |
| Size of Study (possible biases confounded by small size) | High risk | < 50 participants per treatment arm |
Waller 1994.
| Methods | Prospective controlled, single centre study Method of randomisation: none Study duration: admission to hospice until death | |
| Participants | Palliative care patients admitted to hospice, in whom blood and urine samples were collected ≤ 48 hours before death | |
| Interventions | 68 patients were randomised to 1 of 2 groups
|
|
| Outcomes | State of consciousness: no significant difference between groups | |
| Notes | Rinck score = 1.5 Methodological problems:
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Not randomised |
| Allocation concealment (selection bias) | High risk | Not randomised |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Not blinded |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Not stated |
| Selective reporting (reporting bias) | Unclear risk | Insufficient information |
| Size of Study (possible biases confounded by small size) | High risk | < 50 participants per treatment arm |
bpm: beats per minute; FACIT‐F: Functional Assessment of Chronic Illness Therapy ‐ Fatigue; FACIT‐G: Functional Assessment of Chronic Illness Therapy ‐ General; IV: intravenous; MDAS: Memorial Delirium Assessment Scale; MMSE: Mini Mental State Examination; NuDESC: Nursing Delirium Screening Scale; RASS: Richmond Agitation Sedation Scale; VAS: visual analogue scale.
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Morita 2002 | Prospective controlled study examining fluid status of terminally ill cancer patients with intestinal obstruction. Excluded because there was no comparisons between groups with regards to hydration |
| Morita 2006 | Multicentre, prospective, observational study examining artificial hydration therapy, laboratory findings and fluid balance in terminally ill patients with abdominal malignancies. Excluded because there was no comparison between the symptoms of the hydrated and non‐hydrated groups |
Contributions of authors
Phillip Good: formulated question, wrote protocol, searched for studies, reviewed titles and abstracts, retrieved articles, assessed article quality, wrote review, wrote update.
Russell Richard: reviewed titles and abstracts, assessed article quality, performed critical revision of review.
William Syrmis: reviewed titles and abstracts, assessed article quality, performed critical revision of review.
Sue Jenkins‐Marsh: reviewed titles and abstracts, assessed article quality, performed critical revision of review.
Jane Stephens: reviewed titles and abstracts, assessed article quality, performed critical revision of review.
Sources of support
Internal sources
No sources of support supplied
External sources
-
National Institute for Health Research, UK.
NIHR Directly Commissioned Cochrane Incentive Scheme 2013 Award Reference Number 13/180/04.
Declarations of interest
None known.
Stable (no update expected for reasons given in 'What's new')
References
References to studies included in this review
Bruera 2005 {published data only}
- Bruera E, Sala R, Rico MA, Moyano J, Centeno C, Willey J, et al. Effects of parenteral hydration in terminally ill cancer patients: a preliminary study. Journal of Clinical Oncology 2005;23:2366‐71. [DOI] [PubMed] [Google Scholar]
Bruera 2013 {published data only}
- Bruera E, Hui D, Dalal S, Torres‐Vigil I, Trumble J, Roosth J, et al. Parenteral hydration in patients with advanced cancer: a multicenter, double‐blind, placebo‐controlled randomized trial. Journal of Clinical Oncology 2013;21(1):111‐8. [DOI: 10.1200/jco.2012.44.6518] [DOI] [PMC free article] [PubMed] [Google Scholar]
Cerchietti 2000 {published data only}
- Cerchietti L, Navigante A, Sauri A, Palazzo F. Hypodermoclysis for control of dehydration in terminal‐stage cancer. International Journal of Palliative Nursing 2000;6:370‐4. [DOI] [PubMed] [Google Scholar]
Morita 2005 {published data only}
- Morita T, Hyodo I, Yoshimi T, Ikenaga M, Tamura Y, Yoshizawa A, et al. Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies. Annals of Oncology 2005;16:640‐7. [DOI] [PubMed] [Google Scholar]
Viola 1997 {published data only}
- Viola RA. Studying Fluid Status and the Dying: The Challenge of Clinical Research in Palliative Care [MSc thesis]. Canada: University of Ottawa, 1997. [Google Scholar]
Waller 1994 {published data only}
- Waller A, Hershkowitz M, Adunsky A. The effect of intravenous fluid infusion on blood and urine parameters of hydration and on state of consciousness in terminal cancer patients. American Journal of Hospice & Palliative Care 1994;11:22‐7. [DOI] [PubMed] [Google Scholar]
References to studies excluded from this review
Morita 2002 {published data only}
- Morita T, Tei Y, Inoue S, Suga A, Chihara S. Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational study. Supportive Care in Cancer 2002;10:474‐9. [DOI] [PubMed] [Google Scholar]
Morita 2006 {published data only}
- Morita T, Hyodo I, Yoshimi T, Ikenaga M, Tamura Y, Yoshizawa A, et al. Artificial hydration therapy, laboratory findings, and fluid balance in terminally ill patients with abdominal malignancies. Journal of Pain & Symptom Management 2006;31:130‐9. [DOI] [PubMed] [Google Scholar]
Additional references
Abernethy 2003
- Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ 2003;327(7414):523‐8. [DOI] [PMC free article] [PubMed] [Google Scholar]
Ashby 1995
- Ashby M, Stoffell B. Artificial hydration and alimentation at the end of life: a reply to Craig. Journal of Medical Ethics 1995;21(3):135‐40. [0306‐6800 (Print)] [DOI] [PMC free article] [PubMed] [Google Scholar]
Bozzetti 1996
- Bozzetti F, Amadori D, Bruera E, Cozzaglio L, Corli O, Filiberti A, et al. Guidelines on artificial nutrition versus hydration in terminal cancer patients. European Association for Palliative Care. Nutrition 1996;12(3):163‐7. [DOI] [PubMed] [Google Scholar]
Breitbart 2002
- Breitbart W, Tremblay A, Gibson C. An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 2002;43(3):175‐82. [DOI] [PubMed] [Google Scholar]
Casarett 2005
- Casarett D, Kapo J, Caplan A. Appropriate use of artificial nutrition and hydration‐fundamental principles and recommendations. New England Journal of Medicine 2005;353(24):2607‐12. [DOI] [PubMed] [Google Scholar]
Craig 1994
- Craig GM. On withholding nutrition and hydration in the terminally ill: has palliative medicine gone too far?. Journal of Medical Ethics 1994;20(3):139‐43; discussion 144‐5. [0306‐6800 (Print)] [DOI] [PMC free article] [PubMed] [Google Scholar]
Dev 2012
- Dev R, Dalal S, Bruera E. Is there a role for parenteral nutrition or hydration at the end of life?. Current opinion in supportive and palliative care 2012;6(3):365‐70. [PUBMED: 22801468] [DOI] [PubMed] [Google Scholar]
Doyle 2004
- Doyle D, Hanks G, Cherny NI, Calman K. Oxford Textbook of Palliative Medicine. 3rd Edition. Oxford: Oxford University Press, 2004. [Google Scholar]
Good 2014
- Good P, Cavenagh J, Mather M, Ravenscroft P. Medically assisted nutrition for adult palliative care patients. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD006274.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Higgins 2011
- Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Jadad 1996
- Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12. [DOI] [PubMed] [Google Scholar]
Lanuke 2003
- Lanuke K, Fainsinger RL. Hydration management in palliative care settings‐a survey of experts. Journal of Palliative Care 2003;19(4):278‐9. [PubMed] [Google Scholar]
Morita 1998
- Morita T, Ichiki T, Tsunoda J, Inoue S, Chihara S. A prospective study on the dying process in terminally ill cancer patients. American Journal of Hospital Palliative Care 1998;15(4):217‐22. [DOI] [PubMed] [Google Scholar]
Raijmakers 2011
- Raijmakers NJ, Fradsham S, Zuylen L, Mayland C, Ellershaw JE, Heide A. Variation in attitudes towards artificial hydration at the end of life: a systematic literature review. Current opinion in supportive and palliative care 2011;5(3):265‐72. [PUBMED: 21738035] [DOI] [PubMed] [Google Scholar]
Rees 2003
- Rees E, Hardy J. Novel consent process for research in dying patients unable to give consent. BMJ 2003;327(7408):198. [DOI] [PMC free article] [PubMed] [Google Scholar]
Rinck 1997
- Rinck GC, Bos GA, Kleijnen J, Haes HJ, Schade E, Veenhof CH. Methodologic issues in effectiveness research on palliative cancer care: a systematic review. Journal of Clinical Oncology 1997;15(4):1697‐707. [DOI] [PubMed] [Google Scholar]
WHO 2005
- World Health Organization. WHO definition of palliative care. www.who.int/cancer/palliative/definition/en/ (accessed 3 April 2014).
References to other published versions of this review
Good 2008
- Good P, Cavenagh J, Mather M, Ravenscroft P. Medically assisted hydration for adult palliative care patients. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD006273.pub2] [DOI] [PubMed] [Google Scholar]