Introduction

Major emergencies in children younger than 5 years of age occur because of gastrointestinal disturbances.1 Annually, approximately 760,000 children die of diarrheal diseases worldwide, and dehydration is the most common complication of these cases.1,2 Dehydration consists of loss of body water and electrolytes.3 Children need a greater volume of water than adults to maintain body fluid balance. In addition, children are particularly susceptible to dehydration because of a higher metabolic rate; hence, fluid loss can occur rapidly, decreasing intravascular volume.2,4,5 To confirm this diagnosis, a health professional performs a physical examination to determine the severity and cause of the dehydration. The severity of dehydration is classified as severe, some dehydration or no dehydration, following the most commonly used Gorelick scale6 and World Health Organization7 classification.

The oral and intravenous (IV) routes are usually used for fluid replacement to reverse dehydration, but these routes have contraindications. The oral route cannot be used in patients with persistent nausea or vomiting, whereas the IV route is a complex procedure not recommended in children because they have greater capillary fragility, with smaller blood vessels that are more difficult to visualize or palpate than those of adults.8,9

Hypodermoclysis (HDC) is a technique used for the infusion of fluids and electrolytes via subcutaneous tissue,10-13 and is indicated for patients with mild to moderate dehydration who have contraindications to oral administration or have difficult venous access.14,15 Hypodermoclysis is often used for elderly patients and in palliative care even though there are no restrictions on its use in children.16-18 However, HDC is contraindicated in the following groups: patients with severe dehydration, because they require large volumes with rapid infusion that can overwhelm the subcutaneous tissues during absorption; patients with coagulation disorders, edema, anasarca or circulatory failure; patients on hemodialysis; and patients at emergency situations, among others.13,14,19 Fluid infusion by HDC and assessment of the site of infusion must be performed by a trained nurse. A needle catheter (scalp) is inserted into the hypodermis, the deepest layer of the skin. The recommended sites are the anterior region of the thorax, deltoid, scapula, abdomen or anterior and lateral thighs. The catheter should be small caliber and inserted at a 45 degree angle from the skinfold.14,15,20-22

Absorption by the subcutaneous tissue is systemic, gradual and uniform, and occurs through capillary diffusion, tissue perfusion and hydrostatic and osmotic pressures through various blood capillaries and lymphatic vessels present in the tissue. This mechanism varies depending on the individual's blood circulation status.2,13 Capillary diffusion refers to the unrestrained movements of molecules in the body in different directions, including water molecules and substances dissolved in body fluids. This movement promotes the collision of one molecule against the other. Tissue perfusion is the transport of nutrients and oxygen to different body tissues via blood flow.23,24

The total volume that can be administered subcutaneously, according to international manuals, is 1500 mL to 2000 mL every 24 hours in one site and up to 3000 mL in two different insertion sites.13-15 In Brazil, the National Cancer Institute only allows a simultaneous infusion of up to 2 L.19 The infusion rate should be 20 mL to 80 mL per hour considering the occurrence of edema and other adverse events.15,19,25 Given the previously mentioned mechanism of absorption, only water-soluble and pH-neutral drugs can be infused, avoiding hypertonic or hypotonic solutions without electrolytes, as these may harm the patient and result in tissue damage.15,16,19,26 Fluids recommended for this route are 0.9% saline (SF), 5% glycerol serum, Ringer's lactate, sodium chloride and potassium chloride solutions. For drug infusion, they should be in liquid state and diluted 100% (1 mL of medication for 1 mL of diluent) in water for injection or in 0.9% SF.13,19,20,25,26

The adverse events associated with HDC may present as signs of inflammation, hardening, bruises, tissue necrosis (late complication), extravasation, bleeding, pruritus, abscess, fever, chills, aches, headache, anxiety and signs of delayed overload (tachycardia, jugular swelling, hypertension, cough and dyspnea).13,16,19,20,25

Compared with other routes of administration, HDC has numerous advantages, such as less pain; no limb immobility required; low incidence of infection; greater convenience for the patient, family and healthcare team because of its simplicity, low cost and feasibility; the need for only a simple puncture, reducing the discomfort of repeated attempts and resulting in shorter infusion time, especially in the emergency room; and the ability to be performed in a hospital environment by the nursing team or in the patient's home by a trained caregiver with minimal equipment and technical support. For these reasons, HDC has potential for use in children with dehydration.14-16,18,23,27,28 Studies have reported that adverse events from HDC are rare, but if observed by the care team, the infusion should be discontinued or the infusion rate decreased so that the patient may stabilize.29-31

A preliminary search of JBI Database of Systematic Reviews and Implementations Reports, Cochrane Database of Systematic Reviews, PROSPERO and PubMed revealed that no systematic reviews were conducted on the effectiveness of HDC in children until November 2017. It is necessary to increase awareness of the efficiency of HDC as an alternative route for rehydration, with less physical and psychological trauma compared with other parenteral routes traditionally used in children. Therefore, this review is justified by the need for reliable evidence supporting the effectiveness of HDC in children. We aim to synthesize the evidence to determine whether the results uphold the effectiveness of HDC for fluid infusion in children with dehydration.

Review objective/question

The objective of this review is to summarize the published evidence regarding the effectiveness and safety of hypodermoclysis in comparison to intravenous fluid infusion for the rehydration of children with mild or moderate dehydration in hospital and home settings.

The question of the review question is: How do the safety and effectiveness of hypodermoclysis compare to those of intravenous fluid infusion for the rehydration of children presenting with mild to moderate dehydration at hospital or home settings?

Inclusion criteria

Participants

The review will consider studies that include infants and children aged 0 days to 10 years32 with mild or moderate dehydration based on the score using the Gorelick assessment of dehydration level (mild dehydration = 1-2; moderate = 3-6).6 Studies of pediatric populations receiving palliative care will be excluded.

Intervention

This review will include studies that evaluated fluid infusion by HDC at hospitals or at home. The included studies will not be limited by the health professional or trained caregiver who administered the intervention or by the infusion site, duration or volume administered in mL/kg.

Comparator

This review will consider studies that compare the intervention to fluid infusion by the IV route, as it is the gold standard for the treatment of dehydration.31

Outcomes

This review will consider studies that include the following outcomes: dehydration level, safety and pain. These outcomes will be evaluated in terms of the following:

i. Dehydration level will be measured as follows:

* The volume of fluid infused in 24 hours

* Improved dehydration according to the scales for dehydration in children6,7

* Reduced signs and symptoms of dehydration, including general condition (e.g. lethargy, drowsiness, postural dizziness, cold or cyanotic extremities), radial pulse (e.g. weak, filiform, feeble or impalpable), deep or rapid respiration, absence of tears, reduced urine output or no urine output for many hours, capillary refill time at fingertip more than two seconds6 and changes in patient's weight.31

ii. Safety will be evaluated according to the report of the following adverse events: edema, phlebitis, cellulitis and erythema are among the most usual13,30,31; however, studies will not be limited solely to these adverse events.

iii. Pain will be verified according to the pediatric pain scales: the Face, Legs, Activity, Cry, and Consolability scale for children < 3 years old and the Faces Pain Rating Scale for children >=3 years old.31

Types of studies

This review will consider experimental study designs, including randomized controlled trials. In the absence of randomized controlled trials, we will consider other designs including quasi-experimental studies such as non-randomized controlled trials. Also, observational studies such as prospective and retrospective cohort studies, case-control studies and case series studies will be included.33

Studies published since database inception will be considered for inclusion in this review. Studies published in English, Spanish and Portuguese will be considered for inclusion in this review.

Methods

Search strategy

The search strategy aims to find both published and unpublished studies. An initial limited search of PubMed and CINAHL has been undertaken, followed by the analysis of the text words contained in the title and abstract as well as the index terms used to describe article. This informed the development of a search strategy, which will be tailored for each information source. A full search strategy in PubMed is detailed in Appendix I. The reference list of all studies selected for critical appraisal will be screened for additional studies.33

Information sources

The databases and sources to be searched will include PubMed, CINAHL, Web of Science, Embase and Scopus. The search for unpublished studies will include ProQuest Dissertations and Theses Database, EThOS, OpenGrey, DART-Europe E-theses Portal and Trove. The trial registers to be searched will include Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Australian Clinical Trials register, Australian New Zealand Clinical Trials Registry, European Clinical Trials Register, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register and Brazilian Registry of Clinical Trials (ReBec).

Study selection

Following the search, all identified citations will be collated and uploaded into the bibliographic software Mendeley Desktop (Mendeley Ltd., Elsevier, Netherlands), and duplicates will be removed. Titles and abstracts will then be screened by two independent reviewers for assessment comparing them with the inclusion criteria defined for the review. Studies that may meet the inclusion criteria will be retrieved in full and their details imported into JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI; Joanna Briggs Institute, Adelaide, Australia).33 The full text of the selected studies will be retrieved and assessed in detail against the inclusion criteria. Full-text studies that do not meet the inclusion criteria will be excluded, and reasons for exclusion will be provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. Any disagreements that arise between the reviewers will be resolved through a discussion or by a third reviewer.33 The results of the search will be reported in full in the final report and presented in a PRISMA flow diagram.34

Assessment of methodological quality

Selected studies will be critically appraised by two independent reviewers at the study level, analyzing their methodological quality using the standardized critical appraisal instruments from JBI SUMARI33 for the following study types: randomized controlled trials, quasi-experimental studies (non-randomized experimental studies), cohort studies, case-control studies and case series. Any disagreements that may arise will be resolved through a discussion or by a third reviewer. All studies, regardless of their methodological quality, will undergo data extraction and synthesis (where possible).33

Data extraction

Data will be extracted from papers included in the review by two independent reviewers, using the standardized data extraction tool available in JBI SUMARI.33 The data extracted will include specific details about the interventions, populations, study methods, outcomes of significance to the review question and specific objectives. Any disagreements that may arise between the reviewers will be resolved through a discussion or by a third reviewer. Authors of papers will be contacted to request missing or additional data when required.33

Data synthesis

Quantitative data will be pooled in a statistical meta-analysis using JBI SUMARI whenever feasible. All results will be subject to double data entry by two separate reviewers, and a third reviewer will be called to arbitrate in the case of discrepancies. Effect sizes will be expressed as odds ratios (for dichotomous data) or weighted (or standardized) mean differences (for continuous data), and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-squared and I² tests. The choice of model (random or fixed effects) and method for meta-analysis will be based on the Joanna Brigg's Institute Reviewer's Manual.33 The random effects model will be used for meta-analysis if there are at least five studies included in the meta-analysis, whereas the fixed effects model will be used if there are fewer than five studies included in the meta-analysis.35 Heterogeneity will also be explored using subgroup analysis based on the different study designs included in this review. If data are available and can be pooled, a subgroup analysis will be explored based on the grouping of studies that will test the intervention by type of participant(s) according to age. A sensitivity analysis will be conducted to test decisions made regarding each comparison that has a meta-analysis. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. Statistical tests for funnel plot asymmetry (Egger, Begg, and Harbord tests) will be performed, where appropriate.33

Assessing certainty in the findings

We plan to follow the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for grading the quality of evidence. A Summary of Findings will be created using GRADEpro software (McMaster University, ON, Canada). The table will present the following information, where appropriate: absolute risks for treatment and control, estimates of relative risk and a ranking of the quality of the evidence based on study limitations (risk of bias), indirectness, inconsistency, imprecision and publication bias.33 The following outcomes will be included in the summary of findings: dehydration level, safety and pain.

Appendix I: Search strategy for PubMed

References