Received Date : 01-Apr-2016

Revised Date : 09-Nov-2016

Accepted Article
Accepted Date : 03-Dec-2016

Article type : Original Article

How and why are subcutaneous fluids administered in an advanced illness

population: a systematic review

Concise title: Subcut fluid administration in advanced illness

Authors:

Liz Forbat, PhD, MSc, PG Cert, BA (hons). Professor of palliative care, Calvary Health Care and
Australian Catholic University. Calvary Health Care, Clare Holland House, 5 Menindee Drive, Barton,
Canberra, ACT 2600, Australia. elizabeth.forbat@acu.edu.au @lizforbat

Natalie Kunicki, Undergraduate nursing student, Australian Catholic University, Antill Street, Watson,
Canberra, ACT, Australia. natalie.kunicki@myacu.edu.au

Michael Chapman, MBBS. Consultant Palliative Medicine, Canberra Hospital, Yamba Drive,
Canberra, ACT, Australia. mchapmanonline@gmail.com

Clare Lovell, RN, Palliative care nurse. Calvary Health Care, Clare Holland House, 5 Menindee Drive,
Barton, Canberra, ACT 2600, Australia clare.lovell@calvary-act.com.au

Correspondence: Professor Liz Forbat, Director for the Centre of Palliative Care Research, Calvary
Health Care, Clare Holland House, 5 Menindee Drive, Barton, Canberra, ACT 2600, Australia.
Telephone: +61 (0) 26273 0336
Email: elizabeth.forbat@acu.edu.au

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/jocn.13683
This article is protected by copyright. All rights reserved.
 No conflict of interest has been declared by the authors.
Accepted Article
Funding statement: This study was conducted with financial support through an internship
programme of the Australian Catholic University.

ABSTRACT
Aims and objectives. To identify the mechanisms of subcutaneous fluid administration in advanced
illness.

Background. Hydration at end of life is a fundamental issue in quality care internationally. Decision-
making regarding the provision of artificial hydration in advanced illness is complicated by a paucity
of evidence-based guidance. Despite considerable attention given to the topic including two recent
Cochrane reviews, there has been no focus in systematically identifying papers that report the
mechanisms for delivering hydration subcutaneously. Consequently, there is a need to produce
guidance on the site, mode, volume and rate of infusion, based on empirical evidence.

Design. Systematic review of papers reporting empirical research data.

Methods. Key databases (CENTRAL, Medline, Embase, Web of Science, CINAHL) were searched in
September 2015, with no date limitations. Inclusion criteria focused on Hypodermoclysis in adults
within an advanced illness population. Selected studies were reviewed for quality and a risk-of-bias
assessment was conducted for the included studies.

Results. Fourteen papers were included in the analysis, most (n=8) were conducted in hospices with
others (n=6) in long-stay units with a population affected by chronic conditions associated with
ageing. Studies were of moderate or high quality. The site and mode of infusion were not well
described in these papers, and rates of infusion varied widely allowing for little clear consensus to
guide clinical practice in the administration of subcutaneous fluids.

Conclusions. Studies under-report the mechanisms by which artificial hydration is provided, creating
a paucity of evidence based guidance by which to practice. There is a need for evidence generated
from non-malignant populations to ensure applicability to the large number of people with other
advanced illness.

Relevance to clinical practice. In the absence of sufficiently powered robust evidence, the mode of
delivery of artificial hydration at end of life remains in the gloaming between evidence and
unfounded habit.

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 SUMMARY BOX

What does this paper contribute to the wider global clinical community?
 This study draws attention to the lack of empirical evidence informing the site, mode, volume,
Accepted Article
frequency and contraindications of hypodermocylsis in an advanced illness population.
 Despite considerable attention given to artificial hydration in palliative populations there is a
paucity of empirically-informed clinical guidelines, which is a substantial deficit for providing
evidence-based care for people at the end of life.

KEYWORDS
Systematic review, advanced illness, hydration, palliative care, subcutaneous, hypodermocylsis.

INTRODUCTION
Artificial hydration in palliative care is an internationally researched and reported phenomenon
(Groenewoud et al. 2000, Ke et al. 2008, George & Dimond 2009, Krishna et al. 2010, Valentini et al.
2014). Hypodermocylsis (HDC), the subcutaneous delivery of fluids, is offered when patients are no
longer able to take fluids orally, and who have mild to moderate dehydration. Subcutaneous
administration is less costly and less invasive with fewer complications than intravenous hydration
and can be managed in a community setting (Lopez & Reyes-Ortiz 2010). Despite considerable
attention given to the topic, there appears to be a dearth of literature which offers an evidence base
for the mechanisms for delivering such hydration subcutaneously. Consequently, there is a need to
produce guidance on the site, mode, volume and rate of infusion, based on empirical evidence.

Background
Older people with advanced illness are admitted to hospital for managing symptoms related to
dehydration (Xiao et al. 2004, Wotton et al. 2008). Without proper hydration, common
complications such as delirium, urinary tract infections, and behavioural changes can occur (Lawlor
et al. 2000, Nakajima et al. 2014).

The use of HDC varies by culture; the use subcutaneous hydration is part of routine practice in some
settings, particularly in residential care homes and community settings (Sasson & Shvartzman 1998).
In countries such as the UK, Australia and Italy, a psycho-educational approach is adopted with
patients and families, to present the balance of affordances and constraints of providing hydration
near end of life (Mercadante et al. 2005).

A considerable body of research has examined the ethical ramifications of providing artificial
hydration (AH) (Geppert et al. 2010) for this patient group, in both acute care (Higgins et al. 2014)
and advanced-disease settings such as dementia care (Bryon et al. 2012). Cochrane reviews have
identified insufficient evidence for claims that AH in palliative care extends quality-of-life or life-
expectancy (Good et al. 2008, Good et al. 2014).

This article is protected by copyright. All rights reserved.

 Despite the ongoing debates regarding when AH should be used, HDC is often used in the palliative
population. A number of papers report guidelines (Gabriel 2014) and clinical reflections on
administering AH to people with advanced illness (Zembrzuski 1997, Wilson 1999, Nakajima et al.
Accepted Article
2014) . However, while some studies have sought to quantify the precise amount of fluid required
for a long term care population (Culp et al. 2004), there remains inadequate evidence about the
appropriate method for HDC, for patients unable to take fluids orally. Clinical guidelines have sought
to summarise the rationale, amount, timing and content of parenteral hydration (Moriarty & Hudson
2001) and produced clinical guidelines (Morita et al. 2007, Broadhurst 2012), but have not offered a
full description of the evidence base regarding infusion methods.

Without evidence regarding fluid volumes and mode of delivery, generated from a population of
people with advanced illness (rather than a purely palliative population), efficient delivery of AH in
the community is precluded. While other reviews have reported the efficacy of hydration (Good et
al. 2008, American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care
Committee 2014, Good et al. 2014), this paper reports a review examining the details of how HDC is
provided to a palliative population, in the context of empirical research studies. The paper therefore
addresses a concern raised by Frisoli et al, who state that the reason why HDC is not routinely
offered is due to lack of familiarity with the techniques (Frisoli et al. 2000). This paper reports a
systematic review of empirical evidence, from any study-design, regarding the methods and process
of administering subcutaneous fluids in a population with advanced illness.

AIMS
The aim of this review was to address the question: What are the mechanisms of delivery, location
of infusion, duration of site use, quantity and type of subcutaneous fluids administered in an
advanced illness population?

METHODS
Design
An integrative systematic literature review was conducted. The report of this search is based on the
principles of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
(Moher et al. 2009, CRD 2008), and the process is illustrated in the PRISMA flow-diagram in Figure 1.

Research method
A preliminary search was carried out in one database to establish appropriate key words/phrases.
Search terms included medical subject headings terms, free text terms, limiting fields and truncation
symbols were developed by the research team. Inclusion and exclusion criteria were developed to
focus the search on English language papers reporting research on human adults with advanced
illness receiving subcutaneous (rather than intravenous) hydration of fluids, not medications. Table 1
summarises these criteria. Specific search terms are indicated in Table 2 and were designed by
building on the published search strategy of a recent Cochrane review focused on efficacy of AH
(Good et al. 2014). Our search was designed to identify not just patients receiving specialist palliative
care, but also those in residential facilities who may receive generalist palliative support as they
approach end-of-life.

This article is protected by copyright. All rights reserved.

 The main search was conducted in September 2015, using key databases (CENTRAL, Medline,
Embase, Web of Science, CINAHL). A sample search strategy is provided in Appendix A. Titles and/or
abstracts of studies were retrieved using the search strategy and screened independently by two
Accepted Article
review authors to identify studies that potentially meet the inclusion criteria outlined above. The full
text of these potentially eligible studies were retrieved and also independently assessed for
eligibility by two review team members. Any disagreement over the eligibility of particular studies
was resolved through discussion with a third reviewer.

A standardised form was used to extract data from the included studies for assessment of study
quality and evidence synthesis. Extracted information included: study setting, study population and
participant demographics and baseline characteristics, details of the intervention and control
conditions, study methodology, recruitment and study completion rates, outcomes and times of
measurement, indicators of acceptability to users, suggested mechanisms of intervention action,
and information for assessment of the risk of bias. Critically, data were also extracted for the
site/mode of infusion, the volume/rate of infusion and the frequency/duration of infusion.

Two review authors extracted data independently, discrepancies were identified and resolved
through discussion (with a third author where necessary). Although a hand search of papers had not
been part of the original study design, this process was added in after the full texts had been read,
since these included full text articles identified a number of papers which appeared to have
relevance to this search.

Quality assessment and risk of bias was assessed using Critical Appraisal Skills Programme (CASP)
criteria relevant to the design of the study (Critical Appraisal Skills Programme 2013). There was no a
priori quality threshold and no papers were excluded on grounds of quality. Assessment was
undertaken to ensure transparency in the process, ensuring that relevant papers were not excluded
due to limitations in the authors’ reporting (Campbell et al. 2011, Lewin et al. 2015). Quality
assessment was therefore used to provide commentary on the overall rigour and robustness of the
synthesis of all included articles (Lewin et al. 2015), which is particularly salient for articles published
prior to the standardisation of reporting of studies advocated by the EQUATOR network (EQUATOR).
A narrative summary of quality and bias is presented in Table 3, to address the inherent limitations
of comparison across methodologically diverse studies (Whittemore & Knafl 2005).

Analysis was conducted drawing on synthesis of mixed method studies (Joanna Briggs Institute
2014). Since the papers were heterogeneous, statistical pooling of results was not appropriate or
possible, and consequently the findings were summarized in narrative form. The complexity of
analysis of mixed method syntheses has been described (Heyvaert et al. 2013), but since this review
sought to extract data on process rather than outcomes of studies, analysing across diverse study
designs was not deemed problematic.

The review was lodged with PROSPERO (ref: CRD42015026331). Bibliographic software, Endnote X7,
was used to organise the papers identified in the search.

RESULTS
Fourteen studies were included in the analysis, with publication dates ranging from 1994-2014.
Studies varied in their designs from systematic reviews, randomised controlled trials, and
retrospective surveys of practice. Most studies were of moderate (n=4) or high (n=4) quality. Table 3

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 contains a summary of the included studies. Most studies (n=8) were conducted in specialist
palliative care settings with cancer patients, though others (n=6) were conducted in long-stay units
with a population of people with cognitive impairments or other chronic conditions associated with
Accepted Article
ageing (O'Keeffe & Lavan 1996, Worobec & Brown 1997, Dasgupta et al. 2000, Claisse et al. 2005,
Fonzo-Christe et al. 2005, van Wigcheren et al. 2007).

The site and mode of infusion were not well described in these papers, with only five studies
reporting both site and mode (Bruera et al. 1996, O'Keeffe & Lavan 1996, Bruera et al. 1999, Frisoli
et al. 2000, Fonzo-Christe et al. 2005). A further two studies reported only site (Worobec & Brown
1997) or mode (Bruera et al. 2013). Table 4 summarises the site and mode of infusion for these
studies. Since some studies were published, the mode of administration has changed in routine
practice from steel to plastic needles, and is indicated as a shift in some administration in studies
where the steel needles were causing irritation (Bruera et al. 1996). One study used a volumetric
pump (Fonzo-Christe et al. 2005), another stated that it was a ‘pump’ without further description
(Bruera et al. 2013).

The site of infusion was reported with a range of locations, including most frequently the anterior
thoracic or abdominal wall (Bruera et al. 1996, O'Keeffe & Lavan 1996, Frisoli et al. 2000) thighs
(Worobec & Brown 1997, Frisoli et al. 2000, Fonzo-Christe et al. 2005) and back (Frisoli et al. 2000,
Fonzo-Christe et al. 2005). Other sites included arms or hips (Worobec & Brown 1997, Fonzo-Christe
et al. 2005).

Rates of infusion were extracted, with a wide range evident, from 20ml/hour (Dasgupta et al. 2000)
to 2,400ml/day (Lanuke & Fainsinger 2003). Some papers reported continuous night time infusions
(Bruera et al. 1996), continuous over two days (O'Keeffe & Lavan 1996) with others reporting shorter
durations such as four hours (Bruera et al. 2013). Durations of infusions also varied considerably
from three weeks to six months (Claisse et al. 2005), or one-to-three days in van Wigcheren’s (2007)
study where 79% of patients fell within this range. Table 3 presents all studies’ reported volumes,
rates and durations of infusion.

In two studies, the authors reported studies examining the efficacy of hyaluronidase on hydration
(Bruera et al. 1996, Bruera et al. 1999), while another paper from the same author described the
infusion as saline (Bruera et al. 2013). The remaining studies did not specify the content of the
infusion (though as noted in the methods section, studies reporting infusion of medications were
excluded from the review).

Of the fourteen studies, eight reported findings from a palliative population and six from long term
care settings or with an elderly community population (O'Keeffe & Lavan 1996, Dasgupta et al. 2000,
Frisoli et al. 2000, Claisse et al. 2005, Fonzo-Christe et al. 2005, van Wigcheren et al. 2007). There is
therefore a slight bias in the literature in evidence generated from palliative, rather than the general
aging population.

Medical contraindications of commencing or continuing HDC were documented in some studies.

Primarily, these contraindications were in-line with published guidance, such as oedema, renal
failure or poor tissue perfusion (Frisoli et al. 2000, Claisse et al. 2005). However, a considerable
number of studies did not indicate exclusion criteria or contraindications (Bruera et al. 1996, Bruera
et al. 1999, Lanuke & Fainsinger 2003, van Wigcheren et al. 2007) or provided only cursory details,

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 such as ceasing HDC due to patient becoming restless (Worobec & Brown 1997). Consequently, the
papers often provide insufficient detail for replication or for guiding clinical practice through
developing policy of standard operating procedures.
Accepted Article
DISCUSSION
This paper extends recent systematic reviews on hydration in advanced illness in two ways. First, this
review explicitly sought to include populations not routinely accessing specialist palliative care
services, such as nursing home residents. Second, the review focused on the process, rather than
outcomes, of HDC administration.

The site and mode of delivery of HDC is opaque in many research studies. Although empirical
evidence regarding site and mode of delivery is thin, this has not stopped a wealth of papers offering
advice on fluid volumes (Sasson & Shvartzman 1998), use of hyaluronidase (a protein added to
infusions to aid absorption) (Bruera et al. 1995) or administration procedures (Molloy & Cunje 1992).

This review points to the need for more detailed reporting in AH studies, regarding the process of
HDC administration. The lack of detail on the rate, volume, site and mode of infusion creates
uncertainty for clinicians and services unfamiliar with the technique. Such uncertainty presents
unnecessary additional difficulties for clinicians who are already managing the complex interplay of
ethical (Jacobs 2003, Jacobs & Taylor 2005), sociological (McInerney 1992) and medical factors
(Zembrzuski 1997) in decision-making about providing AH for people with advanced illness. The need
to determine best practice in all forms of care for people with advanced life-limiting illness is
increasingly pressing, in the context of the demographic profile of aging populations. Hydration
necessarily will be part of this, including determining best modes of delivery of HDC.

In particular, there is a need for more evidence to be generated from populations beyond those
receiving specialist palliative care to ensure applicability of findings to the large number of people
with other advanced illness. Rigorous research should be conducted to determine a wide-range of
practice issues. For example, ascertaining appropriate fluid volumes for people who have heart
failure and kidney failure who do not have prescribed fluid restrictions as there is a paucity of
evidence regarding volumes in this population. Further, there is currently limited evidence (and none
available from the papers in this review) regarding site use duration, the need for site rotation,
choice of administration method and its relationship with adverse reactions (for example by pump in
the anterior abdominal wall). Further, there was no available evidence on appropriate methods of
HDC in populations whose symptoms contribute to complexities in administration (such as people
with behavioural and social symptoms of dementia, or delirium). Further research into the
appropriate methods of HDC is additionally required to progress understanding of the efficacy and
suitability of this practice. The absence of an accepted approach to HDC contributes to the
difficulties in constructing an evidence base for efficient practice within populations with advanced
illness.

With more robust and diverse evidence, it will be possible to support people to remain in their own
homes and communities, by treating mild dehydration in the community using subcutaneous
methods. Such work has potential to add to the growing drive to reduce hospitalisations (Author &
Author in press).

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 Our study had several limitations. The search criteria did not include proctoclysis (a method of rectal
drip infusion, not routinely used in developed countries) and therefore may have missed studies
conducted in developing nations or remote areas where there is not routine access to other hospital
Accepted Article
equipment used for HDC. The review is limited by searching and reporting only English-language
papers. The exclusion of evidence from culturally and linguistically diverse populations may mean
that we have omitted learning from some countries and cultures. It is possible that at screening
stage of this review, articles were inappropriately excluded due to our own socio-cultural lens of the
language used; for example, papers were excluded if they reported ‘nutrition’, but nutrition may
have been a label applied to fluids with an additive (for example, Berger 1984).

CONCLUSION
The literature demonstrates the breadth of responses to HDC use including considerable debate
about the ethical parameters of providing artificial hydration (Huang & Ahronheim 2000), and
whether it should be used as a quality standard indicator (Long et al. 2013). Despite its acceptance
as routine practice in some areas, until sufficient evidence has been generated to form definitive
guidance on the efficacy of hydration in advance illness, it is wise to provide HDC by drawing on best
evidence regarding the method of administration. However, as this review has identified studies
under-report the mechanisms by which AH is provided, creating a paucity of evidence based
frameworks to guide practice. Future reporting of AH studies should increase the rigour of their
reporting by specifying the site, mode, volume, frequency and contraindications of HDC in a
population with advanced illness.

RELEVANCE TO CLINICAL PRACTICE

There is a paucity of evidence which demonstrates the most appropriate site, mode, frequency and
volume of artificial hydration for people with advanced illness. Clinicians therefore can only operate
using sub-optimal information. Guidelines have not been derived from robust clinical studies
examining the affordances and constraints of different approaches, which presents a substantial
dilemma for providing evidence-based care for people at the end of life.

In the absence of sufficiently powered robust clinical trials, clinicians could be producing their own
evidence, by carefully documenting and monitoring how AH is administered and reporting
conclusions regarding best practice and contraindications. Without such locally derived evidence,
the mode of delivery of AH at end of life will remain in the gloaming between evidence and
unfounded habit.

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Worobec G & Brown MK (1997): Hypodermoclysis therapy. In a chronic care hospital setting. Journal
of gerontological nursing 23, 23-28.
Wotton K, Crannitch K & Munt R (2008): Prevalence, risk factors and strategies to prevent
dehydration in older adults. Contemporary Nurse 31, 44-56.
Xiao H, Barber J & Campbell ES (2004): Economic burden of dehydration among hospitalized elderly
patients. American Journal Of Health-System Pharmacy: AJHP: Official Journal Of The
American Society Of Health-System Pharmacists 61, 2534-2540.
Zembrzuski CD (1997): A three-dimensional approach to hydration of elders: administration, clinical
staff, and in-service education. Geriatric Nursing 18, 20-26.

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Accepted Article

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 Table 1: Inclusion and exclusion criteria


Accepted Article
Hypodermoclysis
Inclusion criteria  Advanced illness
 Sample is ≥18years old
 Administration of subcutaneous fluids for hydration (with results
separable from IV infusion)
 Humans
 All dates
 English language papers only

 Extravasation
Exclusion criteria  Acute illness
 Intravenous therapy
 Syringe driver
 Grasby pump
 Nikki pump

Table 2: Search terms

Terms for advanced illness Location of care Terms for infusion

Advanced disease Aged care facility Electrolytes

Palliative Nursing home Crystalloid
Palliative care Care home Subcutaneous
Specialist palliative care Residential home Fluid intake
Dementia Hospice Dehydration prevention and
Frailty Hospice care control
Delirium Hospital
Urinary tract infection Home based palliative care
Community nursing

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ccepted Articl
Table 3: Characteristics of included studies

Reference Design Purpose of Participants/ Volume/ Frequency/ Exclusion/ Findings Quality and bias
study clinical context Rate of infusion duration contraindications
Bruera et Retrospective To compare 290 consecutive (a) for 62 patients The duration Some participants Mean hydration Moderate.
al. (1996) case-note the volume patients in a (32%), continuous of site of excluded due to was higher in the However: reason
comparative and duration palliative care unit HDC at rates of 40- infusion was dying, discharge, palliative care for giving HDC
study. of hydration in a cancer centre 100 ml/h. reviewed in refusal to group rather than IV is
Patients of palliative were screened. Hyaluronidase was the case of 100 start/continue (2080_+720 not described;
receiving HDC care patients 203 patients added at consecutive HDC, beginning to ml/day, P<0.001). Rationale for why
were with that of a received HDC. concentrations of patients, and tolerate oral fluids. some patients had
compared with similar series 150-300 units/1. found to be However, day time and
a cohort of patients Comparison group 5.2±2.8 days. Contraindications duration of others overnight
receiving IV admitted to a n=30 received IV (b) For 98 patients not clearly HDC in the hydration not
hydration. cancer fluids. (48%) overnight described. palliative care described; unclear
centre. HDC at rates of 60- unit was not why
Participant 120 ml/h. statistically hyaluronidase
characteristics are Hyaluronidase was different to the was used in some
reported for the added at control group instances.
290 cohort, rather concentrations of (P>0.2).
than 203. 150-300 units/1.

(c) For 43 patients

(21%) a bolus of
500 ml solution
over 1 hour, one to
three times a day.
Hyaluronidase, 150
units, was injected
into the
subcutaneous site
before the infusion.
Bruera et Controlled Study the 21 patients with 500ml either with Fluids Some patients No difference Moderate.
al. (1999) trial effectiveness advanced cancer in or without 150 administered excluded due to identified in the However: on a
comparing and number a palliative care units of twice daily for death, swelling or patient comfort two day, cross
HDC with or of adverse unit. All patients hyluronidase. a duration for request. for HDC with or over trial, it seems

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ccepted Articl without a
bolus 150cc
hyaluronidase.
events
associated
with
received overnight
HDC. Rate not described.
2 days.
Contraindications
not elaborated.
without
Hyaluronidase.
inappropriate to
draw too many
conclusions
Hyaluronidas No further
e as a bolus screening process
before noted.
beginning
HDC. Patient age: 64 ± 11
years. Eight
patients were
female. Mix of
tumours.

Bruera et Double-blind Determine 129 patients with Normal saline 1L or HDC was given Contraindications: There was no High
al. (2013) RCT, placebo- whether advanced cancer a placebo of normal twice daily severe difference to
controlled, hydration from 6 hospices. saline 100mL was dehydration, renal quality of life,
multicenter affected 47% female, 60% delivered, over 4 failure, congestive survival or
study. symptoms of white and 59% hours. heart failure, or symptoms of
dehydration, with opioid use. history of bleeding hydration
quality of life disorders. between the two
and survival. groups.
Some participants
were later
excluded due to
death, withdrawal,
refusal and
inability to
complete
outcomes.
Claisse et Prospective Whether Survey of Usual practice was Duration was Only patients who HDC was almost Low. The research
al. (2005) and chronic HDC paramedic and 1000mL overnight. stated at 3 received HDC for always used to question was
descriptive is used to medical teams to weeks to 6 longer than 3 maintain focused on
study, manage gather months. weeks were vital functions whether
consisting of a symptoms or qualitative included. (31/34), rather hydration
review of prolong life. assessment of their than prolong life artificially
patient opinion regarding Contraindications (3/34). extended life.
records and a patients’ situation not clearly However, the data
survey. and use of HDC. described is descriptive and

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ccepted Articl 34 patients were
identified. 22 in
regarding inclusion
criteria.
with no control
group it is not
possible to
short- and medium- directly report on
stay units, and 12 the impact.
in long-term care.

Predominantly
female cohort;
mean age of 87.6,
SD of 7.2.

56% of patients
had a stroke and
50% had cognitive
impairment.
Dasgupta Prospective Compare use Of possible 658 Rate of 20-75ml/hr HDC was Patients were HDC was High. However,
et al. observational of IV residents, 55 were administered excluded due to associated with data is largely
(2000) study. hydration to deemed eligible for daily or as receiving blood fewer fluid- subjective. No
HDC in the study. required basis products or only related rationale provided
treating Patient group: for n=6 one 8 hr shift of complications for why lab data is
acute, mild to mean age participants. fluid therapy, GI compared to IV. not used in all
moderate 83.5±10.5, 40% bleeding or HDC p=0.04 patients.
dehydration female and 37% The mean primarily for No blinding.
in a long with dementia. duration was analgesic
term care 21 days. administration.
setting. Setting: joint n=10 excluded
chronic care and from study in total.
nursing home
facility. HDC was
contraindicated in
life threatening
conditions.
Fainsinger Prospective, To clarify the 100 consecutive The mean volume The mean Patients were HDC is a useful High. Although no
et al. observational indications patients who died in 24 hours was hours of HDC excluded if they and safe method p values are
(1994) study and use of while admitted to 1203 ±505mLs. in a day was had a bleeding of hydrating presented, lab
HDC in the palliative care 17±6. disorder or pre- terminally ill results after HDC
palliative unit from Dec 1990 The mean rate/hr existing oedema. patients. are shown

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ccepted Articl care. – Nov 1991.

Patients consisted
was 72 ±18 mls. Frequency was
not described. HDC was
discontinued then
alongside
baselines

of 54% male with restarted due to:

an average age of Increased oral
66 ±13 in the HDC intake n= 14, pt
group n=69 and request n=1,
65% male with an pulmonary oedema
average age of after receiving 3 U
67±10 in the non packed cells n =1.
HDC group n=31.
Discontinued for
good: death n= 60,
oedema n= 3, local
allergic reaction to
hyluronidase n=2,
renal failure n=2,
inappropriate
secretion of ADH
n=1, family request
n=1.
Fonzo- Postal Examine Geriatric Volume of 250- Frequency was Exclusion criteria HDC was Moderate. The
Christe et questionnaire HDC and department of a 1000mL and many times a not clearly frequently systematic review
al. (2005) of HDC and subcut drug university hospital maximum of day but described. administered for component
drug use by use, consisting of 26 2000mL per day. precise details palliative patients, searched only
doctors and including units, 404 beds Authors did not not given. Contraindications cancer patients medline and
nursing teams rationale, with a mean age of specify amount per were reported as and people with embase. Results of
in geriatric frequency, 85 and a mean stay patient. Range 1-21 oedema (36%), central nervous the different
hospital; mode and of 40 days. days. Mean infection (28%) system disorders. studies are not
systematic problems Rate was not duration of 7 and coagulation Nurses felt HDC clearly
review encountered. described. days. disorders (15%). was given daily; distinguishable.
doctors reported Recall bias
it used weekly. impacts
credibility on
frequency of HDC
administration.
Frisoli et A systematic Assess the The patient group The majority of Frequency and Primary reason for HDC is a safe and Low. Search was
al. (2000) review evidence for consisted of studies used a drip duration was excluding HDC was effective method of Medline only.

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ccepted Articl evaluating the
evidence base
on
administerin
g HDC in an
elderly and
dehydrated elderly
people and those
with terminal
rate of 75-150 ml/h
or did not adjust
the flux so it could
not described. lack of familiarity
with health care
professionals.
to administer
fluids in the
elderly for mild to
No discussion of
quality/bias in
reporting.
administering terminal cancer. freely adjust to its moderate
HDC and on cancer own speed, affected Contraindications dehydration and
treating population. The clinical context by gravity and included in those with
dehydration was varied. subcutaneous coagulation cancer.
tissue absorption. disorders, severe
hydrolectrolytic
Maximum volume disturbances, HDC
administered was as an access path
<3litres/24hours. for the
administration of
colloid or
macromolecular
solutions, and the
limit of liquid that
may be infused in
24 hours.
Good et al. A systematic To determine All studies included Volume was stated Frequency was Patients were The small number High.
(2008) review of RCTs whether patients with as 1000ml stated at 2 excluded in of identified
and medically advanced cancer, compared with days (Bruera Cherchetti study articles meant
prospective assisted and 3 studies 100ml placebo 2005) and due to that no
controlled hydration in (Bruera 2005; (Bruera 2005) and daily uncontrolled, recommendations
studies of palliative Cherchetti 2000; 1000mL in both (Cherchetti, bowel obstruction for practice were
medically care patients Viola 1997) only Cherchetti (2000) Viola 1997) requiring surgery made.
assisted effects included and Viola (1997). and severe
hydration in quality and participants in Duration was constipation.
palliative care length of life. whom it was Rate was not described.
patients. thought the 42ml/hour for Viola 1997
participants were Cherchetti but not excluded patients
dehydrated. stated for the other who were
studies. receiving enteral
tube feedings, had
acute renal failure,
pulmonary oedema
or bleeding
disorders, were

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ccepted Articl aphasic, or had a
MMSE <24.

Good et al. Updated To determine One additional Volume was stated Frequency not Details were not There is High.
(2014) systematic whether study was as 1000mL / clearly described for insufficient
review of RCTs medically identified: Bruera 100mL placebo described for Bruera 2013. evidence of high
or prospective assisted 2013 (Bruera 2013). Bruera 2013. quality. Therefore,
controlled hydration in recommendations
studies of palliative Rate was not Duration was for practice
medically care patients stated. not described. cannot be made.
assisted effects
hydration in quality and
palliative care length of life.
patients.
Lanuke National Understand Patient Volume was 200- Frequency and Exclusion criteria Findings show Low. Unclear how
and survey of 18 the use of characteristics not 2400mL but rate duration not and low use of HDC participants were
Fainsinger Canadian HDC in described clearly. not stated. described. contraindications (median 6-10%). recruited (and
(2003) palliative care palliative not included. Primarily for subsequent bias),
doctors about care setting. Settings included opioid induced small sample size
administering palliative care delirium, and recall bias.
HDC. units/hospice, hypercalcemia Provision of
acute care consult and thirst. artificial
service and home hydration (AH)
setting. varies
considerably. No
explanatory
factors offered, so
is therefore
difficult to draw
firm conclusions
about how and
why AH is offered
O'Keeffe RCT To compare Participants were Up to 2L of fluid The infusion Patients were Results support High. No blinding
and Lavan comparing the tolerance split into the HDC was infused. was excluded if they that HDC is in this study.
(1996) HDC with IV and n=30 or the IV continuous for required IV cheaper than IV
1996 fluids in 60 effectiveness group n=30. Rate was not 2 days. medications, if and just as
patients with of IV versus stated. more than 2L of effective in
cognitive HDC fluids. The HDC group: fluid was needed treating confused

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ccepted Articl impairment
who required
parenteral
mean age of 81 (SD
of 6). 57% were
female and 43%
during the 24hr
period, if there was
evidence of poor
patients who
require fluids.

fluids for at had agitated tissue perfusion

least 48 hours. behaviour. and if the amount
of fluid
The IV group: mean administered had
age of 84 (SD of 7). to be precise due to
67% were female critical reasons;
and 33% were such as heart
agitated. failure.

This study situated Contraindications

an acute geriatric were not clearly
department. described.
van Retrospective To examine Patients had a Volume and rate of Frequency not Exclusions and HDC is practiced Moderate. Design
Wigcheren Study using a the incidence mean age of HDC not stated. described. contraindications less in the not well
et al. postal of Artificial 81±6.7; 71% were were not Netherlands described. Bias
(2007) questionnaire nutrition & female, 50% had Duration was mentioned. compared to the not discussed,
sent to all hydration in Alzheimer’s. most USA. The most recall issues may
nursing-home nursing Reason for giving commonly important have impacted
doctors in the home HDC was an noted at 1-3 consideration quality of data.
Netherlands patients with intercurrent days (79%). when deciding to
n=1054. dementia. infectious disease administer was
at 57%. the patient’s
physical
The setting was condition,
nursing homes with expected result
dementia facilities and wishes of the
in the Netherlands. patient.

Worobec Descriptive Investigate Participants were Volume was not Frequency and Exclusion criteria When HDC is used Low. The study
and Brown study of the use of 67% female and stated. duration of were not stated. on patients who size was very
(1997) residents in a HDC to solve with an average age HDC was not meet the inclusion small (n=12) and
chronic care reversible of 78. Most common rate stated. HDC was ceased on criteria, it is a safe potentially subject
setting of short-term ordered was a patient who and effective to recall bias. The
whom HDC acute fluid 42% were from a 75ml/hr. became restless. No procedure for patient population

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ccepted Articl had been
ordered in
1995.
deficit
problems.
palliative care
program (n=5),
33% behavioural
further details
were given.
rehydration. was
heterogeneous.

health program
(n=4) and 25%
stroke and rehab
program (n=3).

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 Table 4: Site and mode of infusion
Accepted Article
Study
Bruera et al. (1996)
Bruera et al. (1999)
Bruera et al. (2013)
Fonzo-Christe et al. (2005)
Site
Most frequently, the anterior
thoracic or abdominal wall.
Most frequently, chest or
abdomen wall.
Site of infusion not stated.
The sites used were thighs (96%),
back (23%) or arm (18%).
Mode
25-gauge steel butterfly needle. 28
patients (10%) had the steel needled
replaced by a Silastic needle to
manage site irritation.
25-gauge steel butterfly needle used
in all cases.
Use of a pump to deliver HDC.
A volumetric pump was used to
administer HDC.

Butterfly and/or venflon were used.

Frisoli et al. (2000)
O'Keeffe and Lavan (1996)
Worobec and Brown (1997)
The most common sites of HDC A Y kit with butterfly needle was used
were the thigh, chest in males, for administration.
side of the lower abdomen or the
scapular region side of the thorax.
The infraclavicular region, 21-gauge butterfly needle was used.
scapula, abdomen and thigh were
the sites used.
The sites used were the thigh Mode of delivery not stated.
(n=9), abdomen (n=3), scapula
(n=1), hip (n=1) and arm (n=1).

Appendix A: Example search strategy

MEDLINE
1 exp Palliative Care/
2 palliat* .tw
3(end-stage disease* or end stage disease* or end-stage illness or end stage).
4 advanced disease*
5 (incurable illness* or incurable disease*)
6 (terminally ill). SH
7 terminal care. SH
8 (delirium or Urinary Tract Infections or dementia or frail elderly)
9 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 or 8
10 (home nursing or residential facilities or community health nursing or nursing homes or community health
services or skilled nursing facilities or hospitals)
11 (isotonic solutions or electrolytes or Infusions, Subcutaneous or Injections, Subcutaneous, parenteral
nutrition, nutrition therapy, fluid therapy/rehydration solutions) .tw
12 Fluid Therapy/
13 Dehydration/ (9949)
14 (hydrat* or dehydrat* or rehydrat* or (fluid* adj3 therap*) or (fluid* adj3 balance*) or (fluid* adj3 manag*)
or hypodermoclysis).tw.
15 9 OR 10 OR 11 OR 12 OR 13 or 14
16 9 AND 15

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