Characterizing Perfusion and Congestion Responses to Fluid Loading in Critically Ill Septic Patients

NCT07685002 | Not Yet Recruiting

• 1 other identifier: 24AJH-FLUID-IMPACTS
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock

Keywords

sepsis; septic; shock; fluid load; organ dysfunction

Outcome Measures

Primary Outcomes (2)

• Patient classification 1 hour after completion of fluid loading

  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

  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 Outcomes (2)

• Day 28 mortality

  at 28 days

• Identifying pre-fluid loading predictors

  at 28 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Ambroise Paré, APHP

Boulogne-Billancourt, 92100, France

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Shock

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Adrien JOSEPH, MD, PhD

CONTACT

+33 1 49 09 44 09; adrien.joseph@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: July 6, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 6, 2026

Record last verified: 2026-06

Locations

FR (1)