Fluid Intolerance Signals as Safety Limits to Prevent Fluid-induced Harm During Septic Shock Resuscitation

Not Applicable

Recruiting

• Conditions: Septic Shock
• Interventions: Other: Intervention resuscitation; Other: Standard of Care resuscitation

• Registration Number: NCT06568744
• Lead Sponsor: Pontificia Universidad Catolica de Chile

Brief Summary

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

Detailed Description

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.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-21
• Study First Submitted QC: 2024-08-21
• Study Start: 2024-08-22
• Study First Posted: 2024-08-23
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2026-05
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 62

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Intervention resuscitation	This group will follow a resuscitation algorithm aimed at macrohemodynamic stabilization and improvement of tissue hypoperfusion. Fluid administration will be tailored according to fluid responsiveness status, fluid intolerance signals, and hypoperfusion signals such as capillary refill time. Mechanical ventilation and sedation will follow standard management as per current recommendations.
Standard of Care	Standard of Care resuscitation	This group will follow a resuscitation algorithm aimed at macrohemodynamic stabilization and improvement of tissue hypoperfusion. Fluid administration will be tailored according to fluid responsiveness status, and hypoperfusion signals such as capillary refill time. Mechanical ventilation and sedation will follow standard management as per current recommendations.

Primary Outcome Measures

Name	Time	Method
Delta of PaO2: fraction of inspired oxygen (FiO2) ratio between 0-6 hours	6 hours	evolution of lung function during the study period (6h)

Secondary Outcome Measures

Name	Time	Method
Delta of proBNP between 0-6 hours	6 hours	evolution of cardiac function during the study period (6h)
Delta of creatinine between 0-6 hours	6 hours	evolution of renal function during the study period (6h)
Delta of plasma neutrophil gelatinase-associated lipocalin (NGAL) between 0-6 hours	6 hours	evolution of renal function during the study period (6h)
Delta of capillary refill time between 0-6 hours	6 hours	evolution of peripheral perfusion during the study period (6h)
Delta of arterial lactate between 0-6 hours	6 hours	evolution of lactate during the study period (6h)

Trial Locations

Locations (3)

Hospital Biprovincial Quillota-Petorca; 🇨🇱 Quillota, Chile

Hospital Barros Luco; 🇨🇱 Santiago, Chile

Hospital Clinico UC Christus; 🇨🇱 Santiago, Chile