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

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• 24-hour All-Cause Mortality [Time frame: Within 24 hours after initiation of fluid resuscitation]

Secondary outcome measures (7)

• Requirement for Vasopressor Support [Time frame: Within 6 hours after initiation of fluid resuscitation]
• Requirement for Mechanical Ventilation [Time frame: Within 6 hours after initiation of fluid resuscitation]
• Requirement for Emergency Hemodialysis [Time frame: Within 6 hours after initiation of fluid resuscitation]
• Urine Output Response to Fluid Resuscitation [Time frame: Within 6 hours after initiation of fluid resuscitation]
• Change in Serum Lactate Level [Time frame: Baseline and 3 hours after initiation of fluid resuscitation]
• Length of Stay in Intensive Care Unit (ICU) [Time frame: From ICU admission until ICU discharge, assessed up to 30 days]
• Total Length of Hospital Stay [Time frame: From hospital admission until hospital discharge, assessed up to 30 days]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 1 center

• Kutahya City Hospital — Kütahya

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, PMID 34599691

Identifiers

NCT: NCT07240701 · 25-AKD-210

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗