Balanced Crystalloid vs Normal Saline in Pediatric Acute Gastroenteritis

May 22, 2026 updated by: Aykut Çağlar, MD, Aydin Adnan Menderes University

Comparison of Early Biochemical and Clinical Outcomes of Balanced Versus Unbalanced Isotonic Crystalloid in Children Aged 6 Months to 5 Years Who Require Intravenous Rehydration for Acute Gastroenteritis: A Single-Center Prospective Observational Cohort Study

Acute gastroenteritis (AGE) is among the most common reasons for paediatric emergency visits. Children with significant dehydration often require intravenous (IV) fluid therapy. Two main types of IV crystalloid solutions are currently used in clinical practice: 0.9% sodium chloride (normal saline, NS) and balanced crystalloids such as Isolyte-S, which contain acetate and gluconate as bicarbonate precursors.

Normal saline has a high chloride content (154 mEq/L), which may worsen the metabolic acidosis already present in many children with acute gastroenteritis. Balanced crystalloids have a chloride content closer to that of plasma (98 mEq/L) and additionally contain acetate and gluconate, which are metabolised in peripheral tissues to consume hydrogen ions and thereby raise serum bicarbonate - a mechanism distinct from simply avoiding chloride overload.

This study prospectively observes and compares early biochemical and clinical outcomes in children with acute gastroenteritis who receive one of these two fluid types as part of their routine clinical care. The treating physician independently decides which fluid to use; the research team does not influence this decision and does not order any additional tests or procedures. Laboratory values used as outcomes are drawn solely from blood tests obtained as part of standard care.

The primary aim is to determine whether, at approximately 4 hours after IV fluid start, serum bicarbonate has changed more in children who received a balanced crystalloid compared with those who received normal saline. Secondary aims include comparing blood pH, chloride levels, need for additional IV boluses, time to first oral fluid intake, hospitalisation rate, and 72-hour return visits.

Study Overview

Status

Recruiting

Conditions

Detailed Description

BACKGROUND AND SCIENTIFIC RATIONALE Acute gastroenteritis causes gastrointestinal bicarbonate loss through diarrhoea, combined with reduced oral intake and, in severe cases, lactate accumulation from hypoperfusion, resulting in metabolic acidosis.

The conventional choice, 0.9% sodium chloride (NS), carries a supraphysiological chloride load (154 mEq/L versus plasma reference of 98-103 mEq/L). This reduces the strong ion difference (SID), independently precipitating hyperchloraemic metabolic acidosis and failing to correct pre-existing acidosis.

Isolyte-S has a chloride content of 98 mEq/L and contains acetate (27 mEq/L) and gluconate (23 mEq/L) as bicarbonate precursors. Acetate is rapidly metabolised in cardiac muscle, skeletal muscle, and renal cortex independently of hepatic function (half-life approximately 30 minutes) via: CH3COO- + O2 + H+ → 2CO2 + 2H2O, consuming 1 mEq of H+ per mEq of acetate. Gluconate undergoes hepatic oxidation via the pentose phosphate pathway with analogous H+ consumption. The total buffer capacity of Isolyte-S is 50 mEq/L - approximately twice that of Ringer's lactate (28 mEq/L). This active acid-neutralisation capacity is mechanistically distinct from simply avoiding chloride overload.

EVIDENCE BASE The 2023 Cochrane systematic review (Florez et al., 5 RCTs, 465 children) demonstrated improved bicarbonate and pH with balanced crystalloids but judged certainty as low to very low and explicitly called for new adequately powered studies. The meta-analysis by Lehr et al. (2022) reported a pooled delta-HCO3 of +1.60 mmol/L (95% CI 0.04-3.16) favouring balanced fluids in critically ill children. The only RCT using Plasma-Lyte A versus NS in paediatric AGE (Allen et al., 2016) reported delta-HCO3 of +1.6 versus 0.0 mEq/L at 4 hours (p=0.004) but was underpowered for clinical outcomes. No published study has investigated Isolyte-S (acetate/gluconate-buffered, 50 mEq/L total buffer capacity) specifically in children with AGE.

STUDY DESIGN Single-centre, prospective, non-interventional observational cohort study conducted in the paediatric emergency department of Aydin Adnan Menderes University Research and Training Hospital, Turkey (KAD-KLVZ-25). No randomisation, allocation, or investigator-initiated prescribing occurs. The treating physician's independent clinical decision determines group assignment before research consent and enrolment.

STATISTICAL FRAMEWORK

Sample size: 180 total enrolments (anticipated), yielding 126 evaluable participants assuming 70% T4 laboratory availability. Power calculation: minimum clinically important difference delta = 1.5 mmol/L, SD = 3.0 mmol/L, alpha = 0.05 (two-sided), power = 0.80.

Primary analysis: PS-IPTW (propensity score inverse probability of treatment weighting) combined with IPOW (inverse probability of observation weighting) to simultaneously address confounding by indication and informative T4 laboratory missingness. A pre-specified covariate list is fixed prior to data lock. Supporting analysis: multivariable linear regression with robust standard errors (HC3).

Pre-specified mechanistic mediation analysis: causal mediation framework (R package mediation) to partition the total effect on delta-HCO3 into the indirect effect mediated via delta-Cl (hyperchloraemic mechanism) and the direct effect attributable to acetate/gluconate buffering (ACME and ADE). This analysis is exploratory and will be reported as mechanism-consistent association, not causal inference. Seven pre-specified sensitivity analyses are defined in the statistical analysis plan.

Reporting standard: STROBE statement for observational studies. Software: R version 4.3 or later.

DATA COLLECTION Data are recorded on a standardised case report form at three time points: T0 (baseline, at IV fluid start), T4 (3-6 hour window, only if routine laboratory results are available), and 72 hours (electronic health record review for return visits). No study-mandated procedures, tests, or visits are added to the routine care pathway. T4 laboratory values are ascertained exclusively from blood gas or electrolyte results obtained during routine clinical management.

Study Type

Observational

Enrollment (Estimated)

180

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Turkey (Türkiye)
      • Aydin, Turkey (Türkiye), 09100
        • Recruiting
        • Aydin Adnan Menderes University Hospital, Department of Pediatric Emergency Care
        • Contact:
        • Contact:
        • Principal Investigator:
          • Aykut Çağlar, Profesor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Consecutive eligible children aged 6 months to 5 years presenting to the paediatric emergency department of Aydin Adnan Menderes University Hospital with acute gastroenteritis and a clinician-initiated indication for intravenous rehydration. Enrolment is prospective and observational; the treating physician independently determines IV fluid type and dose based on clinical judgment, without involvement from the research team.

Description

Inclusion Criteria:

  • Age: 6 months to 5 years (60 months) inclusive
  • Clinical diagnosis of acute gastroenteritis: acute diarrhoea (3 or more loose stools per 24 hours) with or without vomiting; symptom duration 7 days or less
  • Clinician-initiated indication for intravenous rehydration
  • IV fluid order placed and treatment initiated independently by the treating physician, without research team influence

Exclusion Criteria:

  • Chronic systemic disease (congenital heart disease, chronic kidney disease, chronic lung disease, inborn errors of metabolism, primary immunodeficiency)
  • Hypernatraemic dehydration (serum sodium >= 150 mEq/L at baseline)
  • Diabetic ketoacidosis, primary metabolic crisis, or suspected surgical abdomen
  • Bloody diarrhoea or suspected invasive enteric infection requiring alternative management algorithm
  • Hypoglycaemia (blood glucose < 60 mg/dL) at presentation
  • Symptom duration exceeding 7 days
  • Receipt of 20 mL/kg or more of IV fluid in the 24 hours preceding enrolment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
0.9% Sodium Chloride
Children with acute gastroenteritis who received 0.9% sodium chloride (Na+ 154, Cl- 154 mEq/L) as the initial IV crystalloid, as independently selected by the treating physician. No research-directed intervention.
Balanced Crystalloid (Isolyte-S)
Children with acute gastroenteritis who received an acetate/gluconate-buffered balanced isotonic crystalloid (Isolyte-S: Na+ 141, K+ 5, Mg2+ 3, Cl- 98, acetate 27, gluconate 23 mEq/L) as the initial IV crystalloid, as independently selected by the treating physician. No research-directed intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Bicarbonate (Delta-HCO3)
Time Frame: Approximately 4 hours (3-6 hour window) after IV fluid initiation
Change from baseline in serum bicarbonate concentration (mmol/L) at approximately 4 hours after IV fluid initiation. Defined as HCO3(T4) minus HCO3(T0), where T4 is the routine blood gas or electrolyte measurement obtained 3 to 6 hours after IV fluid start. Analysis performed only in participants for whom T4 laboratory results are available as part of routine clinical care. No additional blood sampling is performed for research purposes.
Approximately 4 hours (3-6 hour window) after IV fluid initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Blood pH (Delta-pH)
Time Frame: 3-6 hours after IV fluid initiation
Change from baseline in arterial or capillary blood pH at approximately 4 hours. Calculated as pH(T4) minus pH(T0). Obtained from routine blood gas analysis only.
3-6 hours after IV fluid initiation
Change in Base Excess (Delta-BE)
Time Frame: 3-6 hours after IV fluid initiation
Change from baseline in base excess (mmol/L) at approximately 4 hours. Calculated as BE(T4) minus BE(T0). Obtained from routine blood gas analysis only.
3-6 hours after IV fluid initiation
Change in Serum Chloride (Delta-Cl)
Time Frame: 3-6 hours after IV fluid initiation
Change from baseline in serum chloride (mEq/L) at approximately 4 hours. Calculated as Cl(T4) minus Cl(T0). Serves as the mediator variable in the pre-specified causal mediation analysis.
3-6 hours after IV fluid initiation
Additional IV Fluid Bolus Requirement
Time Frame: Within 6 hours of IV fluid initiation
Binary outcome: whether the treating physician administered one or more additional IV fluid boluses within 6 hours of initial IV fluid start, as documented in the routine clinical record.
Within 6 hours of IV fluid initiation
Time to First Tolerated Oral Intake
Time Frame: From IV fluid initiation until first tolerated oral intake, assessed up to 24 hours
Time in hours from IV fluid initiation to first documented tolerated oral fluid intake. Censored at 24 hours or at hospital admission, whichever occurs first. Analysed using weighted Cox regression.
From IV fluid initiation until first tolerated oral intake, assessed up to 24 hours
Hospital Admission Decision
Time Frame: From emergency department presentation until disposition decision, up to 24 hours
Binary outcome: whether the treating physician decided to admit the child (observation unit, ward, or ICU), as documented in the electronic health record.
From emergency department presentation until disposition decision, up to 24 hours
72-Hour Emergency Department Return Visit
Time Frame: Within 72 hours of discharge
Binary outcome: unplanned return to the emergency department within 72 hours of discharge, regardless of cause, as identified through electronic health record linkage.
Within 72 hours of discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aydin Adnan Menderes University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2026

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

May 18, 2026

First Submitted That Met QC Criteria

May 22, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADUPEDFluid

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be publicly shared due to Turkish personal health data protection regulations (KVKK). De-identified aggregate summary data will be made available upon reasonable request to the corresponding author following publication.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Vomiting

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe