Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Study Overview
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Brief Summary
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Testing the association between circulating candidate proteins and the level of vascular leakage for three distinct forms of circulatory failure: cardiogenic shock, septic shock, and post-resuscitation syndrome. Describing immuno-inflammatory profiles associated with massive vascular leakage during those three forms of circulatory failure in humans

Detailed Description
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Circulatory shocks are responsible for one third of intensive care unit (ICU) admissions (20,000 patients per year in France) and are associated with 40% mortality [1,2]. Vascular hyperpermeability (also called vascular leakage) is a major feature of circulatory failure. During systemic inflammatory response syndrome (SIRS), massive vascular leakage affects macro and micro-circulation, and participates in the development of multiple organ failure [1,3]. Accordingly, fluid balance (the difference between fluid input and output) correlates independently with mortality during both septic and cardiogenic shock [4-7] and controlling capillary leakage was highly beneficial in numerous animal models of circulatory failure [8-10]. However, the determinants of vascular leakage remain poorly understood in humans. The purpose of this study is to evaluate the link between circulatory levels of several proteins and the level of vascular leakage, in three distinct types of circulatory shocks.

Official Title
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Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Conditions
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Cardiogenic Shock, Postresuscitation Disease, Septic Shock

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent from patient or a legal representative/family member/close relative. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow. Affiliation to social security (AME excluded) Patient with one of the circulatory failures described below: septic shock cardiogenic shock post-resuscitation syndrome Cardiogenic shock: Need for a catecholamine support to maintain mean arterial pressure>65 mmHg, AND Cardiac index <2 L/min/m2 or left ventricular ejection fraction (LVEF)<35%, AND Lactate >2.0 mmol/l Post-resuscitation syndrome: Cardiac arrest (absence of spontaneous respiration, palpable heartbeat, and responsiveness to stimuli> 1 min) with a compatible electrocardiogram (asystole/pulseless electrical activity/ventricular tachycardia), AND Need for a catecholamine support to maintain mean arterial pressure>65 mmHg, AND Lactate >2.0 mmol/l Septic shock: Suspected or proven bacterial infection Need for a vasopressor support to maintain mean arterial pressure>65 mmHg Lactate >2.0 mmol/l Cardiac index>3L/min/m2 or LVEF>40% Exclusion Criteria: Onset of shock (catecholamine infusion) >12 hours prior to inclusion Age <18 year old Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with a circulatory failure<br>All patients hospitalized in ICU with a circulatory failure due to septic shock, cardiogenic shock, or post-resuscitation syndrome. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance from Day 0 to day 3 | (ml/kg of initial body weight). The fluid balance, routinely monitored in ICU, represents fluid intakes (perfusion, oral intakes,..) - fluid losses (diuresis, diarrhea,…) | Between Day 0 and Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance | (ml/kg of initial body weight). The fluid balance, routinely monitored in ICU, represents fluid intakes (perfusion, oral intakes,..) - fluid losses (diuresis, diarrhea,…) | Day 1, Day 3, Day 7, Day 14 | 
| Extra-vascular lung water index | Extra-vascular lung water index (EVLWi, ml/kg) and pulmonary vascular permeability index measured by transpulmonary thermodilution at corresponding time-points | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Serum albuminemia | g/L | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Serum lactatemia | mmoles/L | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Arterial PaO2 | (mmHg) | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Circulating cytokine inflammatory profile IL-33 | (pg/ml) | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Circulating cytokine inflammatory profile TNF-alpha | (pg/ml) | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Circulating cytokine inflammatory profile IL-6 | (pg/ml) | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Circulating cytokine inflammatory profile IL-1 | (pg/ml) | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| SOFA score | Association between circulating candidate proteins, the immune-inflammatory profile of the patients and SOFA score | Day 0, Day 1, Day 3, Day 7, Day 14 | 
| Catecholamine-free days | Number of days alive without receiving any catecholamine | Day 0 to Day 7, Day 30 | 
| Ventilatory-free days | Number of days alive without receiving any machenical ventilation, invasive or non-invasive | Day 0 to Day 7, Day 30 | 
| Renal replacement therapy-free | Number of days alive without receiving any renal replacement therapy | Day 0 to Day 7, Day 30 | 
| Mortality |  | Day 30 |