The goal of this multicentric randomized controlled trial is to compare, in septic shock patients who require further fluid resuscitation, two strategies of administering fluids. The intervention group will integrate fluid intolerance signals to the decision making process, while the control group will follow standard of care, for a 6 hour study protocol. The main question it aims to answer is

1. To compare the effect of both resuscitation strategies on fluid-induced harm, assessed by the change in pulmonary, cardiac, and renal function biomarkers during the study period.
2. To assess the safety of both resuscitation strategies on hypoperfusion resolution, measured by the improvement of capillary refill time (CRT) and lactate during the study period.
3. To determine the dynamics of the different fluid intolerance signals

Fluids are the first-line hemodynamic therapy during septic shock resuscitation, restoring tissue perfusion by effectively increasing cardiac output and oxygen delivery. Nevertheless, resuscitation fluids can be seen as a double-edged sword since they have a narrow therapeutic index. In the one hand, insufficient fluid administration can perpetuate hypoperfusion, leading to irreversible tissue hypoxia, while excessive fluid administration can lead to fluid-induced harm. The extreme scenario of this condition, fluid overload, has been consistently associated with worse clinical outcomes, including increased risks of prolonged mechanical ventilation, acute kidney injury and mortality. As an eminently retrospective diagnosis, it may underestimate the importance of timely recognition of fluid-induced harm during the resuscitation period and could shift clinicians' efforts to treatment rather than prevention. Thus, identifying organ-specific venous congestion signals early on during the resuscitation process is desirable and could avoid these adverse outcomes. Recent studies have shown that venous congestion signals are present even during the first day of ICU admission.

The investigators hypothesized that in critically ill patients with septic shock, a fluid resuscitation strategy that integrates fluid intolerance signals as safety limits will prevent fluid-induced harm, without compromising hypoperfusion resolution, compared to a standard resuscitation strategy.

To confirm this hypothesis, the investigators propose a multicenter prospective randomized controlled study in 62 critically ill patients with septic shock, comparing two strategies for conducting fluid resuscitation, aiming to decrease fluid-induced harm. One strategy will follow the standard of care, while the other will rest on real-time ultrasound-based monitoring of fluid intolerance signals. The latter approach will allow clinicians to limit fluid administration when potentially deleterious signals appear. The impact of both strategies on fluid-induced harm will be assessed by the evolution of key organ function biomarkers, namely lungs, heart, and kidneys during the 6-hour study period. Perfusion dynamics will be assessed by capillary refill time and arterial lactate kinetics during the study period. Patients will receive general monitoring and management according to ICU standards. Patients will be followed-up for 28 days for other relevant outcomes.

Inclusion Criteria:

• Diagnosed or suspected septic shock
• < 24 hours since diagnosis
• Hypoperfusion signal (altered arterial lactate or CRT) that requires further resuscitation
• Mechanical ventilation
• Positive fluid responsiveness status

Exclusion Criteria:

• Pregnancy
• Do-not-resuscitate status
• Acute coronary syndrome
• Active bleeding
• Severe concomitant acute respiratory distress syndrome (ARDS) (PaO2:FiO2 ratio < 100)
• Anticipated surgery, prone positioning, or renal replacement therapy in the next 6 hours
• Refractory shock according to attending physician
• BMI > 40.
• Inadequate echocardiographic window

data sharing will be anonymized upon reasonable request to the corresponding author

After study completion

upon reasonable request to the PI.