Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

• 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

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.

Inclusion Criteria:

1. 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.

2. Affiliation to social security (AME excluded)

3. 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:

1. Onset of shock (catecholamine infusion) >12 hours prior to inclusion
2. Age <18 year old
3. Pregnancy