Normal Saline Versus Ringer's Lactate for Initial Fluid Resuscitation in Sepsis

A Prospective, Single-Center, Randomized Controlled Trial Comparing Normal Saline and Ringer's Lactate for Initial Fluid Resuscitation in Adult Patients With Sepsis in the Emergency Department

This clinical trial aims to determine if the type of intravenous fluid used for initial resuscitation affects the short-term outcomes of adult patients with sepsis who are treated in the emergency department.

The main questions it aims to answer are:

Does using Ringer's lactate instead of 0.9% sodium chloride (normal saline) reduce 24-hour mortality in patients with sepsis?

Does the type of fluid influence other short-term outcomes, such as the need for vasopressors, mechanical ventilation, hemodialysis, and length of hospital stay?

Researchers will compare two groups of participants:

• The Ringer's lactate group (intervention group)
• The 0.9% sodium chloride group (control group).

Participants will:

• Receive either Ringer's lactate or normal saline for initial fluid resuscitation as part of standard sepsis care.
• They will be observed for 24 hours to assess survival and other early outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: Ringer's Lactate; Other: Normal Saline (0.9% Sodium Chloride)

Detailed Description

This prospective, single-center, randomized, double-blind, controlled clinical trial aims to compare the effects of Ringer's lactate and 0.9% sodium chloride (normal saline) solutions for initial fluid resuscitation in adult patients with sepsis who are treated in the emergency department. The study is conducted in accordance with the Surviving Sepsis Campaign's 2021 guidelines, which emphasize the importance of early and adequate crystalloid resuscitation in sepsis management. Although both solutions are widely used in clinical practice, evidence regarding their comparative effects on short-term mortality and organ dysfunction is inconsistent. This study seeks to provide prospective, blinded data to clarify whether fluid type influences early outcomes in patients with sepsis.

Participants who meet eligibility criteria will be randomized in a 1:1 ratio using a computer-generated sequence prepared by an independent staff member. To ensure blinding, study fluids will be provided in identical coded containers, and patients, treating clinicians, and investigators will remain unaware of the assigned fluid type throughout the study period.

The assigned study fluid will be administered intravenously as an initial bolus according to clinical judgment. After completion of the initial bolus, all subsequent fluid therapy and additional treatments will follow standard institutional practice at the discretion of the treating physician.

If clinical circumstances require breaking the study blind for patient safety reasons, the investigator will document the reason and unblind the allocation. There will be no delay in clinical management as a result of study participation.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Egemen Yildiz, MD; Phone Number: +90 (274) 229 14 00; Email: egemen.yildiz94@gmail.com
• Study Contact Backup: Name: Ertan Sonmez, MD, Professor; Phone Number: +90 (274) 229 14 00; Email: ertan.sonmez@ksbu.edu.tr

Study Locations

• Turkey (Türkiye)
  • Kütahya, Turkey (Türkiye), 43100
    • Kutahya City Hospital
    • Contact: Egemen Yildiz, MD; Phone Number: + 90 (274) 229 14 00; Email: egemen.yildiz94@gmail.com
    • Contact: Ertan Sonmez, MD, Professor; Phone Number: + 90 (274) 229 14 00; Email: ertan.sonmez@ksbu.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult male or female patients (≥18 years of age) presenting to the emergency department.
• Diagnosed or suspected sepsis secondary to an infectious cause.
• Provision of written informed consent by the patient, or if the patient is unable to consent, by a first-degree relative or legally authorized representative.

Exclusion Criteria:

• Age under 18 years old.
• Pregnant women.
• Informed consent was not obtained from the patient or their first-degree relative/legal guardian.
• Patients who are receiving cardiopulmonary resuscitation (CPR) or who require endotracheal intubation at the time of presentation.
• Patients with severe volume depletion unrelated to sepsis (e.g., diabetic ketoacidosis, burns, or active gastrointestinal bleeding).
• Patients with severe hyperkalemia (serum potassium level of at least 6.5 mmol/L with ECG changes).
• Patients with hypotension that is not related to sepsis (e.g., active hemorrhage or intracranial bleeding).
• Patients with clinical signs of pulmonary edema or congestive heart failure.
• Cases in which the treating physician determines that one isotonic crystalloid (Ringer's lactate or 0.9% NaCl) is clearly superior to the other due to clinical condition or comorbidities.
• Cases in which the treating physician anticipates that fluid therapy might be delayed due to study participation.
• Patients requiring immediate hospital or ICU admission before completion of initial emergency department resuscitation.
• Patients with sepsis sources requiring urgent invasive intervention known to directly affect mortality (e.g., an undrainable abscess or osteomyelitis).

Additional exclusion criteria based on the contraindications listed in the Ringer's lactate product information:,

• Known hypersensitivity to sodium lactate.
• Extracellular hyperhydration or hypervolemia.
• Severe renal failure with oliguria or anuria.
• Decompensated heart failure.
• Hypercalcemia.
• Metabolic alkalosis or severe metabolic acidosis.
• Conditions associated with impaired lactate metabolism, such as lactic acidosis, severe liver failure, and cirrhosis with ascites.
• Current use of digitalis preparations (e.g., digoxin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ringer's Lactate Group; Eligible participants in this group will receive Ringer's lactate solution as the initial intravenous fluid for resuscitating sepsis. This will be administered through a peripheral intravenous line at a rate of 1000 ml over 30-60 minutes, as determined by the attending physician and the patient's clinical condition. All other treatments will follow standard sepsis care protocols.	Other: Ringer's Lactate; Intravenous infusion of Ringer's lactate solution for initial fluid resuscitation in sepsis. Each participant receives approximately 1000 mL of Ringer's lactate administered via a peripheral intravenous line over 30 to 60 minutes during the initial resuscitation phase. The intervention is performed once, and all subsequent management follows standard sepsis treatment protocols.
Active Comparator: Normal Saline Group; Eligible participants in this arm will receive 0.9% sodium chloride (normal saline) as the initial intravenous fluid for resuscitation in sepsis. This will be administered through a peripheral intravenous line at a rate of 1000 ml over 30-60 minutes, as determined by the attending physician and the patient's clinical condition. All other treatments will follow standard sepsis care protocols.	Other: Normal Saline (0.9% Sodium Chloride); Intravenous infusion of 0.9% sodium chloride solution (normal saline) for initial fluid resuscitation in sepsis. Each participant receives approximately 1000 mL of normal saline administered via a peripheral intravenous line over 30 to 60 minutes during the initial resuscitation phase. The intervention is performed once, and all subsequent management follows standard sepsis treatment protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour All-Cause Mortality	The proportion of participants who die from any cause within 24 hours after receiving the assigned study fluid (Ringer's lactate or normal saline) for initial resuscitation. Mortality will be determined based on hospital medical records.	Within 24 hours after initiation of fluid resuscitation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Requirement for Vasopressor Support	The proportion of participants who receive any vasopressor agents (e.g. norepinephrine, epinephrine or vasopressin) within six hours of initial fluid administration, as documented in the medical record. Will be reported as a percentage.	Within 6 hours after initiation of fluid resuscitation
Requirement for Mechanical Ventilation	The proportion of participants who require endotracheal intubation and mechanical ventilation within six hours of the initial administration of fluids. Will be reported as a percentage.	Within 6 hours after initiation of fluid resuscitation
Requirement for Emergency Hemodialysis	The proportion of participants who require emergency hemodialysis within 6 hours after initial fluid administration. The outcome will be reported as a percentage.	Within 6 hours after initiation of fluid resuscitation
Urine Output Response to Fluid Resuscitation	The proportion of participants with a total urine output of ≥3 mL/kg during the first six hours after receiving the study fluid, as recorded in the patient's follow-up chart. The outcome will be reported as a percentage.	Within 6 hours after initiation of fluid resuscitation
Change in Serum Lactate Level	Change in serum lactate concentration (mmol/L), calculated as the difference between the value at 3 hours and the baseline value obtained before fluid administration. The outcome will be reported as the mean change (mmol/L).	Baseline and 3 hours after initiation of fluid resuscitation
Length of Stay in Intensive Care Unit (ICU)	Duration of ICU stay, measured in days among participants admitted to the ICU after initial fluid resuscitation.	From ICU admission until ICU discharge, assessed up to 30 days
Total Length of Hospital Stay	Total duration of hospitalization, measured in days based on hospital records.	From hospital admission until hospital discharge, assessed up to 30 days

Collaborators and Investigators

• Sponsor: Egemen Yildiz

Publications and helpful links

General Publications

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; sepsis; emergency department; Mortality; Renal Replacement Therapy; Fluid Therapy; Vasoconstrictor Agents; Ringer's Lactate; Crystalloid Solutions; Saline Solution
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Emergencies; Sepsis; Pharmaceutical Preparations; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Sodium Compounds; Chlorides; Hydrochloric Acid; Saline Solution; Sodium Chloride; Ringer's Lactate
• Other Study ID Numbers: 25-AKD-210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the study results will be shared upon reasonable request after publication. Shared data will include demographic, treatment, and outcome variables. Access will be granted to qualified researchers with ethics committee approval and a sound research proposal.
• IPD Sharing Time Frame: De-identified individual participant data (IPD) and supporting documents will be available beginning 6 months after publication of the main results and will remain available for 5 years thereafter. Requests received after this period will be evaluated on a case-by-case basis.
• IPD Sharing Access Criteria: Data will be shared with qualified researchers upon reasonable request. Interested investigators must submit a brief research proposal describing study aims, statistical analysis plan, and data protection procedures. Access will be granted after approval by the institutional ethics committee. The de-identified dataset and relevant documents will be shared electronically via a secure data transfer platform.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No