Volume Kinetics of Fluid Resuscitation in Early Sepsis

Volume Kinetics of Fluid Resuscitation With 30 ml/kg Ringer Lactate in Early Sepsis

The recommended volume resuscitation for patients with early sepsis-induced hypoperfusion is at least 30 ml/kg of crystalloid administered within the first three hours. However, this standardized approach does not account for individual patient variability and lacks personalization. Additionally, the effects of administering 30 ml/kg on intercompartmental fluid shifts between the plasma and interstitial compartments remain unclear. This study aims to describe the volume kinetics of administering 30 ml/kg of Ringer's Lactate in patients with early sepsis-induced hypoperfusion within the first three hours.

Study Overview

• Status: Recruiting
• Conditions: Fluid and Electrolyte Imbalance
• Intervention / Treatment: Drug: Ringer's Lactate

Detailed Description

Adult patients admitted to the intensive care unit (ICU) with sepsis, as defined by the Sepsis-3 criteria, and exhibiting sepsis-induced hypoperfusion prior to receiving adequate volume resuscitation (i.e., 30 ml/kg of crystalloid), are administered Ringer's Lactate at a dose of 30 ml/kg. The initial 20 ml/kg is infused at a constant rate over the first 30 minutes, followed by a 30-minute pause, with an additional 10 ml/kg administered over the subsequent 15 minutes, completing the infusion within 75 minutes.

Up to 180 minutes post-infusion, no other fluids (e.g., gelatin, albumin) are administered except for antibiotics, sedatives, or vasoactive substances as needed. Ideally, only one catecholamine (e.g., norepinephrine) is administered. The volume and quantity of these substances are recorded. Arterial blood samples are collected for blood gas analysis, including hemoglobin levels. Urinary output is measured at 30, 60, and 180 minutes, and any blood loss, other than the 1.5 ml per sample collected, is quantified during hemoglobin monitoring. Additionally, urinary creatinine concentration is determined from urine samples collected at baseline.

The hemodilution data are utilized as input into a three-compartment model with microconstants for fluid redistribution and excretion.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Cosmin Balan, PhD; Phone Number: 0722751501; Email: cosmin13mara@yahoo.com

Study Locations

• Romania
  • Bucharest, Romania, 022328
    • Recruiting
    • "Prof CC Iliescu" Emergency Institue for Cardiovascular Diseases
    • Contact: Cosmin Balan, PhD; Phone Number: +40722751501; Email: cosmin13mara@yahoo.com
    • Contact: Email: cosmin13mara@yahoo.com
    • Principal Investigator: Cosmin Balan, PhD
  • București
    • Bucharest, București, Romania, 022328
      • Recruiting
      • Fundeni Clinical Institute
      • Contact: Sebastian Isac, PhD; Email: sebastian.isac@umfcd.ro
      • Principal Investigator: Sebastian Isac, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult patients admitted in the intensive care unit (ICU) with sepsis, as defined by the Sepsis-3 criteria and exhibiting sepsis-induced hypoperfusion prior to the administration of adequate volume resuscitation.

Description

Inclusion Criteria:

A diagnosis of sepsis, as defined by the Sepsis-3 criteria and exhibiting sepsis-induced hypoperfusion prior to the administration of adequate volume resuscitation:

• hypotension requiring norepinephrine to maintain a mean arterial blood pressure (MAP) either predefined by the clinician or at 65 mm Hg or higher and/or
• a serum lactate level >2 mmol/L (18mg/dL) and/or
• acute oliguria defined as urine output <0.5mL/kg/hr and/or
• mottled skin and/or
• capillary refill time > 3 seconds.

Exclusion Criteria:

• Administration of at least 1 L of IV fluid in the last 6 hours prior to screening. All crystalloids, colloids and blood products that the patient has received are counted.
• Known pregnancy.
• Competing causes of lactic acidosis including: seizures within 3 hours of enrollment, use of linezolid or metformin or anti-retrovirals at the time of enrollment, carbon monoxide or cyanide poisoning, highly suspected or known ischemic bowel, and known mitochondrial disorders.
• End-stage renal disease that requires chronic dialysis.
• Concurrent haemorrhagic or obstructive shock.

• Increased risk of fluid intolerance:

  • Echocardiographic evidence of moderate or severe left ventricular systolic dysfunction.
  • Echocardiographic evidence of moderate or severe right ventricular systolic dysfunction.
  • Hypoxemia index < 200 mmHg or sonographic evidence of bilateral B or C profile.
  • Abdominal compartment syndrome.
• Post-cardiac arrest.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ringer's Lactate; Adult patients admitted in the intensive care unit (ICU) with sepsis, as defined by the Sepsis-3 criteria and exhibiting sepsis-induced hypoperfusion prior to the administration of adequate volume resuscitation (i.e., 30 ml/kg crystalloid).	Drug: Ringer's Lactate; Ringer's Lactate is administered at a dose of 30ml/kg, with the first 20ml/kg given at a constant rate over the initial 30 minutes, followed by a 30-minute pause, and then an additional 10ml/kg over the next 15 minutes, completing the infusion within 75 minutes.; Other Names: Crystalloid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Volume	Plasma volume (ml) was determined using a three-compartment kinetic model with five rate constants (k12, k21, k23, k32 and k10) and a scaling factor (Vc, central volume) that relates dilution to volume. This model was applied to the dependent variables, which included frequently measured plasma dilution and urinary excretion.	180 minutes after the start of the Ringer's Lactate infusion

Collaborators and Investigators

• Sponsor: Institutul de Urgenţă pentru Boli Cardiovasculare Prof.Dr. C.C. Iliescu
• Investigators: Study Director: Serban-Ion Bubenek-Turconi, Professor, "Prof CC Iliescu" Emergency Institue for Cardiovascular Diseases; Study Chair: Robert Hahn, Professor, Karolinska Institutet: Stockholm, SE (Department of Clinical Sciences, Danderyd Hospital) Employment

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 7, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: sepsis; crystalloid; Ringer's Lactate; volume kinetics; volume resuscitation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Pharmaceutical Preparations; Isotonic Solutions; Solutions; Crystalloid Solutions; Ringer's Lactate
• Other Study ID Numbers: 17736

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes