Abbreviations
- HDC
hypodermoclysis
- IV
intravenously
- RCT
randomized controlled trial
- SR
systematic review
Context and Policy Issues
Hypodermoclysis (HDC) is a method of administering fluids or medication subcutaneously (under the skin), as opposed to intravenously (IV; into a vein) or intramuscularly (into a muscle). It is a viable option for many medications and fluids, especially if the individual is unable to take oral medication or if the individual has unsuitable veins for IV fluids.1 Benefits of subcutaneous administration of medication include lower pain (as there are fewer pain receptors), good irrigation, and lower proteolytic activity. However, the bioavailability of substances administered in this method is uncertain. In mild to moderate dehydration, HDC of fluids is a relatively accepted form of rehydration therapy, especially when other routes are inaccessible or ineffective.1 However, HDC can be a costly procedure, and its effectiveness is debated, with a lack of literature or evidence for effectiveness, especially in specific populations.1–3 Therefore, the purpose of this report is to examine the clinical and cost effectiveness of HDC in frail patients or patients residing in long term care, as well as evidence-based guidelines regarding the use of HDC in these patients.
This report is an upgrade of a previous 2020 CADTH report titled “Hypodermoclysis for Frail Patients and Patients in Long Term Care: Clinical Effectiveness, Cost Effectiveness, and Guidelines”,4 therefore it summarizes and critically appraises the articles identified in that report.
Research Questions
What is the clinical effectiveness of hypodermoclysis in frail patients who are at risk of dehydration or who are dehydrated in any setting?
What is the clinical effectiveness of hypodermoclysis in geriatric patients who are at risk of dehydration or who are dehydrated in long term care?
What is the cost-effectiveness of hypodermoclysis in frail patients who are at risk of dehydration or who are dehydrated in any setting?
What is the cost-effectiveness of hypodermoclysis in geriatric patients who are at risk of dehydration or who are dehydrated in long term care?
What are the evidence-based guidelines regarding the use of hypodermoclysis in frail patients or patients in long term care?
Key Findings
Two systematic reviews and one randomized controlled trial were identified regarding hypodermoclysis in patients who are frail or who are in long term care. Hypodermoclysis appeared to have fewer adverse effects or complications when compared with intravenous fluids but did not have a significantly better clinical improvement of dehydration. The studies were of low quality, with poor reporting of methods and small sample sizes. No economic evaluations were identified regarding hypodermoclysis in frail patients or patients in long term care, and no evidence-based guidelines were identified.
Methods
Literature Search Methods
This report makes use of a literature search developed for a previous CADTH report.4 For the previous report, a limited literature search was conducted by an information specialist on key resources including Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, the University of York Centre for Reviews and Dissemination (CRD) databases, the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were hypodermoclysis. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 01, 2015 and June 29, 2020.
Selection Criteria and Methods
One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in .
Exclusion Criteria
Articles were excluded if they did not meet the selection criteria outlined in , they were duplicate publications, or were published prior to 2015. Articles were excluded if they were not clear on the population being examined or were mixed populations with no indication of how many individuals fit the inclusion criteria of this report. Articles were also excluded if the patients were not in long term care (e.g., acute care or palliative care) and were not specified as being frail. Systematic reviews (SRs) in which all relevant studies were captured in other more recent or more comprehensive SRs were excluded. Primary studies retrieved by the search were excluded if they were captured in one or more included SRs. Guidelines with unclear methodology were also excluded.
Critical Appraisal of Individual Studies
The included publications were critically appraised by one reviewer using the following tools as a guide: A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2)5 for SRs and the Downs and Black checklist6 for randomized controlled trials (RCTs). Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
Summary of Evidence
Quantity of Research Available
A total of 65 citations were identified in the literature search. Following screening of titles and abstracts, 62 citations were excluded and three potentially relevant reports from the electronic search were retrieved for full-text review. No potentially relevant publications were retrieved from the grey literature search for full-text review. Of these potentially relevant articles, no publications were excluded, and three publications met the inclusion criteria and were included in this report. These comprised two systematic reviews and one randomized controlled trial. Appendix 1 presents the PRISMA7 flowchart of the study selection.
Additional references of potential interest are provided in Appendix 6.
Summary of Study Characteristics
Additional details regarding the characteristics of included publications are provided in Appendix 2.
Study Design
Two SRs were identified with relevance to the research question and inclusion criteria of this report. Forbat et al2 was published in 2016, including all relevant studies and systematic reviews prior to September 2015. Forbat et al2 included English language studies but were not specific in what study designs were eligible for inclusion. Duems-Noriega and Ariño-Blasco1 was published in 2015, and included “original articles”, reviews, letters to the editor, or communications with no limitation on date published or language, but did not specify what date the search was performed.
The SRs had broader inclusion criteria than this report. Forbat et al2 included studies examining the mechanisms of delivery, the location of HDC, the type of fluids, and the quantity of fluids in patients with advanced illness, which included patients in acute settings and palliative care. Duems-Noriega and Ariño-Blasco included administration of medication subcutaneously as well as fluid administration.1 Only the studies examining relevant population groups and interventions were extracted from these SRs.
There was overlap of one relevant study between the two SRs. The degree of overlap is illustrated in tabular form in Appendix 5.
The included primary study was an RCT with a crossover design, in which the patients received both the intervention and the control, thereby acting as their own controls.8
Country of Origin
The first author of Forbat et al is from Australia.2 The first author for Duems-Noriega and Ariño-Blasco is from Spain.1
The RCT was conducted in Turkey.8
Patient Population
Forbat et al2 included studies examining adults over 18 with advanced illnesses who were receiving subcutaneous hydration, which included patients in a residential facility or aged-care facility (i.e., long term care). Duems-Noriega and Ariño-Blasco1 included studies with patients in long term care and frail elderly patients, but were not clear in what was the overall eligible population was for the SR. The number of relevant participants from Forbat et al2 was 55 for one of the included primary studies, and not reported for the other. In Duems-Noriega and Ariño-Blasco,1 the primary studies included 148 participants.
The population for the RCT (n = 30) was geriatric patients over the age of 65 living in a long term private care facility.8 The majority of patients were female.8
Interventions and Comparators
The relevant interventions in the SRs was HDC.1,2 The eligible comparator for Forbat et al2 was fluid administered through an IV line. The comparator was not specified for Duems-Noriega and Ariño-Blasco,1 but was assumed to be potentially all comparators as the search strategy was broad.
The intervention for the included RCT (Esmeray et al) was three consecutive HDC infusions. The infusions were 1000mL of 0.9% saline solution administrated with a 21- to 23-gauge subcutaneous butterfly needle at a rate of 125mL per hour. HDC was compared to three consecutive IV infusions, but the rate of infusion and the amount of fluid infused was not reported.8
Outcomes
The outcomes eligible for Forbat et al were complications associated with hydrodermoclysis.2 The outcomes for Duems-Noriega and Ariño-Blasco1 were not specified in the methods, but the included primary studies had measured outcomes of urea levels, sodium levels, and creatinine levels, discomfort, feasibility, osmolarity, and function.
The outcomes for Esmeray et al8 were complications or adverse events, the use of consumables, urine density, pH values of urine, and vital signs, but only complications, number of catheters used, duration of catheter use, and time to insert catheter were reported in the results.
Summary of Critical Appraisal
Additional details regarding the strengths and limitations of included publications are provided in Appendix 3
One SR was of moderate quality.2 One SR was of very-low quality,1 as the methodology used to create the SR was unclear.
Forbat et al2 had a clear aim and research question. It also was registered in PROSPERO (a prospective registrar for systematic reviews) prior to the report being completed, showing a priori methods. The SR also did a preliminary search (i.e., scoping search) to determine appropriate inclusion and exclusion criteria for the review.2 The search included multiple databases, and two reviewers both independently selected studies and extracted data.2 However, the review was missing some outcome information, including clinical and functional outcomes that were available in the original primary study abstract, but not reported in the SR. It was unclear why these outcomes were not included, and it was unclear if some results were not included due to selective publishing of results.2
Duems-Noriega and Ariño-Blasco were unclear regarding their methodology.1 The inclusion and exclusion criteria and eligible population groups were unclear, and there was no protocol or a priori methodology provided. There was additionally no information on study selection or data extraction, so it is unknown if bias was introduced in this stage.1 The authors also do not provide an appropriate count of how many studies were identified in the initial search, and how many studies were excluded, therefore making it difficult to determine whether the search yielded an expected number of results for their parameters.1 It is also unclear when the search was performed, so, although assumed to be before 2015 (the publication date of the SR), it is not clear how long prior to publication the search was performed.1 Additionally, details from the results of the studies are missing, such as ages of the patients, ratios of the genders, rates of infusion, and the type of infusion.1
The methodology of the included RCT was poorly reported, therefore its quality is unclear.8 The aim of the study was clear, but the control group was not sufficiently detailed and was not defined adequately.8 It was unclear how much time occurred between infusions and how much time occurred between the intervention and control group (or control and intervention group).8 The randomization technique used is not described, therefore it is not possible to judge whether the randomization was adequate or maintained.8 The authors of the study also reported what outcomes were to be collected, but did not report what methods were used to collect the data, such as what scales were used, what threshold was used to determine what counted as an adverse event, or why some outcomes were included over others.8 Additionally, the authors did not report on all the outcomes mentioned in the methods, namely, urine density, urine pH levels, and patient vital signs. It was not clear why these results were not included.8 Finally, the sample size was relatively small (n = 30), and there was no power calculation performed to determine if the study was appropriately powered to find a significant difference.
Summary of Findings
Appendix 4 presents the main study findings and authors’ conclusions.
Clinical Effectiveness of Hypodermoclysis
What is the clinical effectiveness of hypodermoclysis in frail patients who are at risk of dehydration or who are dehydrated in any setting?
The primary studies included in the SRs were from 2004 or earlier.1,2
One primary study included in Forbat et al2 was a prospective observational study, where frail elderly adults (n = 55) were given HDC at a rate of 20 to 75 mL/h daily, and had fewer fluid-related complications when compared with individuals given IV fluids for dehydration (P = 0.04).2 This prospective study was also included in Duems-Noriega and Ariño-Blasco.1 Duems-Noriega and Ariño-Blasco reported that general or clinical improvement was not statistically different between the groups (P = 0.19), and local reactions were lower in the group receiving HDC.1
Duems-Noriega and Ariño-Blasco1 included one uncontrolled study examining outcomes before and after HDC administration in frail patients. The uncontrolled study examined 57 frail, elderly patients, 77% of which had clinical improvement after HDC (P value not reported).
What is the clinical effectiveness of hypodermoclysis in geriatric patients who are at risk of dehydration or who are dehydrated in long term care?
One primary study identified in Forbat et al2 was an SR which concluded that HDC was safe and effective for older people in long term care with mild to moderate dehydration, but no numerical or statistical results were provided, and it was unclear what HDC was compared to.
One uncontrolled study with 36 patients in a care home found no improvements in serum sodium, urea, or creatinine levels (P values not reported).1 71% of these patients returned to a clinical baseline.1
In the included RCT (N = 30), HDC had fewer complications overall when compared with IV infusion (P = 0.001). Patients had significantly less redness after the first administration of fluid, and the number of patients with agitation and bleeding was fewer after all administrations with HDC compared with IV (P = 0.001 for all).8 The number of catheters used was higher in patients receiving IV fluids and the insertion time was longer when compared with HDC (P = 0.001 for both). However, catheter duration was longer in patients when they received HDC compared with IV (P = 0.001).8
Cost-Effectiveness of Hypodermoclysis
What is the cost-effectiveness of hypodermoclysis in geriatric patients who are at risk of dehydration or who are dehydrated in long term care?
No relevant cost effectiveness evidence regarding the HDC for patients in long term care settings was identified; therefore, no summary can be provided.
What is the cost-effectiveness of hypodermoclysis in frail patients who are at risk of dehydration or who are dehydrated in any setting?
No relevant cost effectiveness evidence regarding the HDC for frail patients was identified; therefore, no summary can be provided.
Guidelines
What are the evidence-based guidelines regarding the use of hypodermoclysis in frail patients or patients in long term care?
No evidence-based guidelines were identified regarding HDC for frail patients or patients in long term care settings; therefore, no summary can be provided.
Limitations
The articles included within this report were relatively outdated – despite the SRs being published in 20151 and 20162 respectively, the articles identified by those reviews were from 2000 and earlier. While studies that are outdated can still provide valuable information, the care provided in those studies and the techniques and equipment used may not reflect current care. Additionally, there were few studies examining HDC in frail patients or in long term care settings. This scarcity of evidence and well conducted studies with many patients in a variety of settings makes decision making difficult, as small studies conducted in specific setting may not be generalizable to all settings or to the Canadian context. The evidence base was limited, and of low quality, as the studies identified may have a high risk of bias. This also limits conclusions that can be drawn from the studies.
Finally, there were no cost studies identified in the literature. This precludes any conclusions that can be made regarding the cost of treatment, and whether any potential clinical effectiveness also translates into cost-related effectiveness for HDC. There were also no evidence-based guidelines identified.
Conclusions and Implications for Decision or Policy Making
Two SRs1,2 and one RCT8 were identified regarding the clinical effectiveness of HDC in patients who are frail or who are staying in long term care. Overall, based on low-quality evidence, HDC showed fewer complications than IV administered fluids. One SR reported on clinical improvement and did not find a statistically significant difference between HDC and IV fluids. There were no economic evaluations or evidence-based guidelines identified in the literature.
The methodology of the two SRs by Forbat et al and Duems-Noriega et al were moderate quality2 and very low quality1 respectively. Methodological and reporting issues with the SRs included missing methodology, outcomes, and results, and unclear data extraction or selection methods. The searches were generally broad and conducted in multiple databases.
The RCT was of low quality.8 It was unclear what the randomization method was, the interventions were unclear, and some outcomes were not reported. There was no justification for any missing outcomes or clarification on methods.
Limitations of the evidence base include relatively outdated studies, low quantity and quality of studies, and small sample sizes in the identified studies. The uncertainty in the evidence and the identified studies means that the conclusions from these studies should be interpreted with caution.
References
- 1.
Duems-Noriega
O, Arino-Blasco
S. Subcutaneous fluid and drug delivery: Safe, efficient and inexpensive. Rev Clin Gerontol. 2015;25(2):117–146.
- 2.
Forbat
L, Kunicki
N, Chapman
M, Lovell
C. How and why are subcutaneous fluids administered in an advanced illness population: a systematic review.
J Clin Nurs. 2017;26(9–10):1204–1216. [
PubMed: 27982484]
- 3.
Dayan
D, Menahem
S, Shvartzman
P. When they stop drinking-examining end-of-life hydration practices and death rattle occurrence.
Support Care Cancer. 2020;23:23. [
PubMed: 32328774]
- 4.
- 5.
Shea
BJ, Reeves
BC, Wells
G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both.
BMJ. 2017;358:j4008. [
PMC free article: PMC5833365] [
PubMed: 28935701]
- 6.
Downs
SH, Black
N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.
J Epidemiol Community Health. 1998;52(6):377–384. [
PMC free article: PMC1756728] [
PubMed: 9764259]
- 7.
Liberati
A, Altman
DG, Tetzlaff
J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
J Clin Epidemiol. 2009;62(10):e1–e34. [
PubMed: 19631507]
- 8.
Esmeray
G, Senturan
L, Doventas
A. A study on efficacy of hydration administered by subcutaneous infusion in geriatric patients. Turk Geriatri Derg. 2018;21(3):438–445.
- 9.
Dasgupta
M, Binns
MA, Rochon
PA. Subcutaneous Fluid Infusion in a Long-Term Care Setting.
J Am Geriatr Soc. 2000;48(7):795–799. [
PubMed: 10894319]
- 10.
Arinzon
Z, Feldman
J, Fidelman
Z, Gepstein
R, Berner
YN. Hypodermoclysis (subcutaneous infusion) effective mode of treatment of dehydration in long-term care patients.
Arch Gerontol Geriatr. 2004;38(2):167–173. [
PubMed: 14698495]
- 11.
Frisoli Junior
A, de Paula
AP, Feldman
D, Nasri
F. Subcutaneous hydration by hypodermoclysis. A practical and low cost treatment for elderly patients.
Drugs Aging. 2000;16(4):313–319. [
PubMed: 10874526]
- 12.
Hussain
NA, Warshaw
G. Utility of clysis for hydration in nursing home residents.
J Am Geriatr Soc. 1996;44(8):969–973. [
PubMed: 8708310]
Appendix 1. Selection of Included Studies
Appendix 6. Further Information
Previous CADTH Reports
- 1.
- 2.
- 3.
Systematic Review Articles – Out of Date Range
- 4.
Rochon
PA, Gill
SS, Litner
J, Fischbach
M, Goodison
AJ, Gordon
M. A systematic review of the evidence for hypodermoclysis to treat dehydration in older people. J Gerontol A Biol Sci Med Sci. 1997;52(3):M169–176.
PubMed: PM 9158559 [
PubMed: 9158559]
Additional References
- 5.
- 6.
- 7.
About the Series
CADTH Rapid Response Report: Summary with Critical Appraisal
Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
Suggested citation:
Hypodermoclysis for Frail Patients and Patients in Long Term Care: A Review of Clinical Effectiveness, Cost Effectiveness, and Guidelines. Ottawa: CADTH; 2020 August. (CADTH rapid response report: summary with critical appraisal).
Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials.
This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.
Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third party supplier of information.
This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own risk.
This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.
