Interstitial Fluid Composition in Patients with Septic Versus Non-septic Shock: an Exploratory Pilot Study

Septic shock is a common reason for admission to intensive care units and severe infections are responsible for 6 million deaths a year worldwide. Fluid management appears to be a major issue in resuscitation and particularly in septic shock, where generalised oedema is almost systematic and is a major factor in poor prognosis during sepsis. The formation of oedema corresponds to an imbalance, according to Frank-Starling's law of the heart, between the vascular compartment and the interstitial compartment, which is composed of the interstitial liquid and an extracellular matrix. This extracellular matrix consists essentially of a network of collagen and fibroblast fibres. Even though all of the plasma in the body transits through the interstitium in 24 hours and desite its major importance in the microenvironment and intercellular communication, the interstitial compartment has not been fully described. In oncology, interstitial tissue seems to contribute to tumour growth through changes in matrix composition and pressure in the interstitium. This pressure actively contributes to the regulation of transcapillary filtration, and thus to the oedema and hypovolemia observed during sepsis. In usual conditions, the fibroblasts exert a tension on the collagen fibres of the matrix via integrin Beta-1 (ITGB1). This tension is released under the action of pro-inflammatory mediators, resulting in negative pressure which potentiates the formation of oedema.

It has been shown in an endotoxemia model that there is a thousandfold higher concentration of ITGB1 in the interstitium compared to the vascular compartment, suggesting a local secretion of this cytokine. The alteration of the extracellular matrix could also play a role in the perpetuation of oedema during septic shock. Considered as an organ in its own right, interstitial tissue is far from playing a passive role between the vascular compartment and the cells. The hypothesis is that interstitial fluid analysis could improve our understanding of the physiopathology of sepsis, in particular on the alteration of the mechanisms of fluid movement regulation, which remains very poorly understood while being closely associated with prognosis in patients with sepsis.


Eligibility Criteria:
Inclusion Criteria:

COMMON INCLUSION CRITERIA

* Patient under mechanical ventilation and sedation
* Patient and/or trusted person (health care proxy) or close relative who has given their oral consent after being informed,
* Age ≥ 18 years old,

INCLUSION CRITERIA FOR THE SEPTIC SHOCK GROUP

* Diagnosis within 24 hours of admission of septic shock as defined by :
* A probable or confirmed infection
* And a SOFA score ≥ 2
* And the need to introduce vasopressors to obtain a MAP ≥ 65 mmHg despite adequate vascular filling
* And an arterial lactate \> 2 mmol/l
* Norepinephrine dose greater than 0.1 μg/kg/min
* Septic shock present for less than 48 hours

INCLUSION CRITERIA FOR THE CONTROL GROUP

- Absence of sepsis and shock from any cause within 2 months prior to inclusion

Exclusion Criteria:

* Disseminated intravascular coagulation (DIC) with haemorrhagic syndrome
* Acute condition that can mimic sepsis :
* Acute pancreatitis without signs of superinfection
* Metformin Intoxication
* Patient with an unfavourable prognosis within 24 hours
* Patient under legal protection (safeguard of justice, guardianship or tutelage)
* Pregnant or breastfeeding women
* Patient not affiliated to national health insurance