Validation of a Capillary Leak Index During Septic Shock, Based on Haemoglobin Level Variations Induced by Fluid Resuscitation. A Pilot Study.

Overview

This study aims to validate a simple and reproducible index of capillary leak (CLI) in septic shock, based on haemoglobin (Hb) variation induced by standardised fluid resuscitation. To achieve this, the correlation between CLI and biomarkers of endothelial dysfunction-angiopoietin-2 and syndecan-1-will be assessed in both septic and non-septic shock patients. CLI may contribute to the individualisation of fluid management in patients with septic shock.

Detailed description

Septic shock is characterised by systemic inflammation leading to endothelial dysfunction and increased capillary permeability. This results in intravascular hypovolaemia and interstitial oedema, contributing to tissue hypoperfusion and organ failure. Despite the prognostic implications, bedside assessment of capillary leak remains difficult, with no simple or standardised method available. Fluid resuscitation is the first-line therapy for circulatory failure in septic shock, but excessive fluid administration has been associated with increased mortality. Recent trials investigating restrictive fluid strategies have failed to show a survival benefit, likely due to the lack of patient stratification based on the severity of capillary leak. A bedside marker could guide personalised fluid and vasopressor therapy.

A standardised fluid bolus (8 ml/kg of ideal body weight, Ringer's lactate) will be administered in both septic and non-septic shock patients. Haemoglobin levels will be measured before and after infusion, and the CLI will be calculated as (Hb pre - Hb post) / Hb pre \* 100. Bioimpedance analysis will be used to estimate extracellular water in selected patients.

Interventions

• Other TEST GROUP: A standardised fluid bolus of 8 mL/kg of ideal body weight using Ringer's lactate will be administered in septic shock patients.
  A standardised fluid bolus of 8 mL/kg of ideal body weight using Ringer's lactate will be administered in septic shock patients. Haemoglobin levels will be measured before and after the infusion, and CLI will be calculated using the following formula: CLI = (Hb pre - Hb post) / Hb pre \* 100 In selected patients, extracellular water volume will be estimated using bioimpedance analysis.
• Other CONTROL GROUP: A standardised fluid bolus of 8 mL/kg of ideal body weight using Ringer's lactate will be administered in non-septic postoperative patients.
  Description: A standardised fluid bolus of 8 mL/kg of ideal body weight using Ringer's lactate will be administered in non-septic postoperative patients. Haemoglobin levels will be measured before and after the infusion, and CLI will be calculated using the following formula: CLI = (Hb pre - Hb post) / Hb pre \* 100

Primary outcome measures

• Correlation coefficient between CLI and serum levels of angiopoietin-2 and syndecan-1 at inclusion (Day 0) and on Day 3 in patients with septic shock. [Time frame: 04 DAYS]

Secondary outcome measures (3)

• Correlation coefficient between CLI at Day 0 and extracellular water accumulation from Day 0 to Day 3, assessed by bioimpedance, in patients with septic shock [Time frame: 04 DAYS]
• Difference in CLI at Day 0 between patients with septic shock and those without. [Time frame: 01 DAY]
• Odds ratio (95% CI) for the association between 30-day mortality and CLI measured at Day 0 in patients with septic shock. [Time frame: 30 DAYS]

Eligibility criteria

Inclusion criteria

• Test group (septic shock patients):
• Adults admitted to the general ICU within 24 hours with a diagnosis of septic shock
• Eligible for blood sampling during daytime hours

Control group (non septic shock patients):

• Adults admitted to the postoperative ICU within 24 hours after surgery
• Need for fluid resuscitation
• Eligible for blood sampling during daytime hours
• Patients with an arterial catheter in place as part of their care

Exclusion criteria

• \- Clarkson's disease (idiopathic capillary leak syndrome)
• Pre-existing extracellular fluid overload (e.g., cirrhosis, decompensated heart failure, nephrotic syndrome, chronic kidney disease on or awaiting dialysis)
• Active bleeding or hemolysis
• Receiving ECMO
• Ongoing renal replacement therapy during the intervention
• Blood transfusion within one hour before the intervention
• Change in vasopressor or inotrope dose within 30 minutes before the intervention

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Martinique · 1 center

• CHUM — Fort-de-France

Identifiers

NCT: NCT07733206 · 25_RIPH2-05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗