Clinical trial NCT06499701: Volume Kinetics of Fluid Resuscitation in Early Sepsis
Official title: Volume Kinetics of Fluid Resuscitation With 30 ml/kg Ringer Lactate in Early Sepsis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fluid and Electrolyte Imbalance
Keywords: volume kinetics
sepsis
volume resuscitation
crystalloid
Ringer's Lactate
Lead sponsor: Institutul de Urgenţă pentru Boli Cardiovasculare Prof.Dr. C.C. Iliescu
Sponsor class: OTHER
First posted: 2024-07-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Volume
timeFrame: 180 minutes after the start of the Ringer's Lactate infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
state: București
city: Bucharest
country: Romania
facility: "Prof CC Iliescu" Emergency Institue for Cardiovascular Diseases
Study officials:
affiliation: Karolinska Institutet: Stockholm, SE (Department of Clinical Sciences, Danderyd Hospital) Employment
name: Robert Hahn, Professor
role: STUDY_CHAIR
affiliation: "Prof CC Iliescu" Emergency Institue for Cardiovascular Diseases
name: Serban-Ion Bubenek-Turconi, Professor
role: STUDY_DIRECTOR
References: