Characterizing Perfusion and Congestion Responses to Fluid Loading in Critically Ill Septic Patients (FLUID-IMPACTS)

June 29, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Sepsis is a leading cause of mortality worldwide and a major contributor to deaths in intensive care units. Early hemodynamic resuscitation, particularly fluid loading, is a cornerstone of septic shock management. However, the benefit-risk balance of fluid administration is difficult to assess in routine practice. Insufficient fluid resuscitation may result in persistent tissue hypoperfusion, organ ischemia, and multiorgan failure, whereas excessive fluid administration is associated with increased mortality, mainly due to systemic venous congestion and organ edema.

The concept of fluid tolerance, defined as the ability of a patient to receive fluids without developing harmful consequences related to fluid overload, is increasingly recognized. Nevertheless, its evaluation remains challenging because of the lack of validated tools and consensual thresholds. In addition, although several markers of tissue perfusion and systemic venous congestion have been described, their combined clinical relevance and prognostic value following fluid loading in septic shock have not been specifically evaluated.

This study aims to assess perfusion and congestion responses to fluid loading in patients with septic shock. The primary objective is to compare patients according to changes in tissue perfusion markers (lactate concentration, mottling score, capillary refill time, venous-to-arterial CO₂ gradient, and central venous oxygen saturation) and systemic venous congestion markers (central venous pressure and hepatic and portal vein Doppler indices) after fluid administration. Secondary objectives include evaluating the evolution of venous congestion markers and their association with organ dysfunction within 48 hours, the relationship between post-fluid loading congestion dynamics and 28-day mortality, and identifying pre-fluid loading predictors of patients who fail to improve tissue perfusion while exhibiting worsening venous congestion.

This is a prospective, multicenter, non-interventional observational cohort study conducted in five intensive care units. Eligible patients are adult patients with septic shock, mechanically ventilated, equipped with arterial and central venous catheters, and presenting a positive passive leg-raising test defined as an increase greater than 10% in cardiac output or left ventricular outflow tract velocity-time integral. All patients receive standard care in accordance with international guidelines, and fluid administration is entirely at the discretion of the treating physician.

Clinical, biological, hemodynamic, and echocardiographic data are collected before and after fluid loading. Patients are retrospectively classified into four groups based on the presence or absence of improvement in tissue perfusion and worsening of venous congestion. Follow-up continues until ICU discharge or day 28.

Approximately 280 patients are expected to be screened to include 170 patients. The results may help identify patients who are fluid responsive in terms of cardiac output but at risk of harmful venous congestion, supporting more individualized fluid resuscitation strategies in septic shock.

Study Overview

Status

Not yet recruiting

Conditions

Septic Shock

Detailed Description

All patients receive standard care in accordance with current international guidelines. The decision to administer fluids, the type of crystalloid, and the infused volume are at the discretion of the treating physician.

Study data are collected at predefined time points before and after fluid resuscitation and include routinely measured clinical, biological, and hemodynamic parameters, as well as echocardiographic Doppler indices of systemic venous congestion. Patients are retrospectively classified into four groups according to the presence or absence of improvement in tissue perfusion markers and worsening of venous congestion markers. Follow-up continues until ICU discharge or day 28, with collection of organ dysfunction scores, fluid balance, and mortality data.

Based on previous data, approximately 280 patients are expected to be screened to include 170 patients, allowing meaningful comparisons across groups. The inclusion period is 23 months, with a 28-day follow-up and a total study duration of 24 months. Statistical analyses will compare groups using appropriate parametric or nonparametric tests, survival analysis using Cox proportional hazards models, and predictive modeling assessed by ROC curve analysis.

Study Type

Observational

Enrollment (Estimated)

170

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

Name: Adrien JOSEPH, MD, PhD
Phone Number: +33 1 49 09 44 09
Email: adrien.joseph@aphp.fr

Study Locations

France
- - Boulogne-Billancourt, France, 92100
    - Hôpital Ambroise Paré, APHP

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

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Patients with septic shock, defined according to proven or suspected infection with hypotension requiring vasopressor therapy, either community or hospital onset.

Description

Inclusion Criteria:

Patients with septic shock, defined according to proven or suspected infection with hypotension requiring vasopressor therapy, either community or hospital onset.
Mechanical ventilation
Central venous catheter in the superior vena cava territory
Arterial catheter in place
Positive passive leg-raising (PLR) test-defined as an increase of >10% in subaortic velocity-time integral-which predicts responsiveness to fluid loading.

Exclusion Criteria:

Contraindication to performing a passive leg-raising manoeuvre (e.g., unstable spinal fracture, intracranial hypertension, critical limb ischemia).
Age < 18 years.
Lack of social coverage or individuals deprived of liberty.
Pregnant women.
Extracorporeal membrane oxygenation (veno-venous or venoarterial)
Cirrhosis with portal hypertension or portal vein thrombosis
Inability to obtain non-opposition from the patient or their legal representative.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient classification 1 hour after completion of fluid loading Time Frame: at 1 hour	The primary objective of the study is to determine the proportion of patients belonging to the four categories defined by changes in tissue perfusion markers and systemic venous congestion markers, one hour after fluid load. Group 1 : Improvement in tissue perfusion markers with no worsening of systemic venous congestion markers Group 2 : Improvement in tissue perfusion markers with worsening of systemic venous congestion markers Group 3 : No improvement in tissue perfusion markers with no worsening of systemic venous congestion markers Group 4 : No improvement in tissue perfusion markers with worsening of systemic venous congestion markers Tissue perfusion will be assessed using blood lactate concentration, central venous oxygen saturation, venous-to-arterial carbon dioxide difference, mottling score and capillary refill time. Systemic venous congestion will be assessed using portal vein pulsatility, hepatic vein doppler S/D ratio and central venous pressure.	at 1 hour
Change in SOFA score from baseline to 48 hours after fluid loading Time Frame: at 48 hours	Assessing the association between the 4 group classification mentionned above and organ dysfunction (defined as a increase in SOFA score components) within the 48 hours following fluid administration.	at 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day 28 mortality Time Frame: at 28 days	Assessing the association between the 4 group classification mentionned above and day-28 mortality.	at 28 days
Identifying pre-fluid loading predictors Time Frame: at 28 days	Identifying pre-fluid loading predictors of belonging to the subgroup of patients who fail to show improvement in tissue perfusion and who demonstrate worsening systemic venous congestion.	at 28 days

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

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 (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

January 22, 2026

First Submitted That Met QC Criteria

June 29, 2026

First Posted (Actual)

July 6, 2026

Study Record Updates

Last Update Posted (Actual)