Impact of an Echographic Algorithm on Hemodynamic Optimization in the First 4 Days of Septic Shock Management

Study Overview
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Brief Summary
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Fluid management is one of the key issues in the initial management of septic shock (SS). Fluid overload and hypovolemia have been associated with increased mortality in several trials. Transthoracic echocardiography (TTE) and lung ultrasound are recommended for haemodynamic assessment in critically ill patients. However, the benefit of hemodynamic optimisation using echography has not been yet evaluated. The purpose of this multicenter, controlled, randomized trial is to assess the impact of an echocardiographic algorithm of hemodynamic optimization on fluid management in septic patients during the first 4 days of therapy.

Official Title
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Impact of an Echographic Algorithm on Hemodynamic Optimization in the First 4 Days of Septic Shock Management: a Multicentric, Randomized, Controlled, Open Label Pilot-study

Conditions
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Shock, Septic, Hemodynamic Instability

Intervention / Treatment
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* Other: Echographic hemodynamic algorithm guiding fluid resuscitation


Participation Criteria
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Eligibility Criteria
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All eligible patients will have a cardiac echocardiogram prior to inclusion for the sole purpose of eliminating special situations that are part of the non-inclusion criteria listed below. Inclusion Criteria Patient in an intensive care unit who develops septic shock on admission or during hospitalization, as defined by SEPSIS-3 criteria. Patient or trusted person / legal representative / family member / curator / guardian who has given free and informed consent and has signed the consent form or patient included in an emergency situation. Patient affiliated or beneficiary of a health insurance plan. Patient at least (≥) 18 years of age. Exclusion Criteria: Refusal of consent. Patient under court protection or guardianship. Moribund patient with a life expectancy of less than 48 hours. Non-echogenic patient. Cardiac tamponade. Infective endocarditis. Intracavitary thrombus. Dilated cardiomyopathy with LVEF (Left Ventricular Ejection Fraction<40%. Parturient or nursing patient.

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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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional Strategy: STOPFLUID Algorithm<br>Fluid management is optimised using the specific echographic hemodynamic algorithm ('STOPFLUID') of this study described during the first 4 days of septic shock. Fluid bolus will not be administered in case of increased left ventricle filling pressures; fluid challenge will be performed based on dynamic indices and fluid depletion will be considered on the basis of Lung UltraSound (LUS) assessment. | Other: Echographic hemodynamic algorithm guiding fluid resuscitation<br>* Ultrasound Hemodynamic Algorithm (UHA): st step: 1/ Assessment of left ventricular filling pressures by Mitral Doppler echocardiography (2) 2/ Pulmonary ultrasound on 4 anterior dials (3) E/Ea >14 and/or E/A >2 YES => No filling test => Bilateral anterior B lines on lung ultrasound => YES => Consider administration of diuretics NO => Step 2 nd step: Assessment of filling response by dynamic maneuvers VTI (Velocity Time Integral) increase >15% after passive leg raising (4) or Mini-fluid challenge (5,6) Or decision of a 250ml filling test YES => consider 250ml bolus filling NO => stop vascular filling rd step if dynamic maneuvers in favor of a response to filling: 1/ Assessment of response to 250ml filling 2/ If no response to vascular filling: Pulmonary ultrasound on 4 anterior dials (3) Change from a pulmonary profile A to a pulmonary profile B YES => depletion NO => stop vascular filling<br>|
| No Intervention: Standard Strategy<br>Fluid management will be handled according to standard care, without using transthoracic echocardiography (TTE) during the first 4 days of septic shock management. Haemodynamic monitoring including pulmonary artery catheter, transpulmonary thermodilution, or any other device will be left at the physician's discretion. TTE will be allowed in the standard group only for excluding cardiac tamponade in case of clinical suspicion (one or more of the following signs: jugular distension, pulsus paradoxus) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of vascular filling during the first 4 days | This takes into account the cumulative volume of vascular filling administered to improve cardiac output during the 4 first days, measured in Liter (L) | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| .Analysis of the primary endpoint related to ARDS ([acute respiratory distress syndrome, according to Berlin criteria) | Analysis of the primary endpoint in relation with presence or absence of ARDS at inclusion | Day 4 | 
| Analysis of the primary endpoint related to severe renal dysfunction | Analysis of the primary endpoint in relation with severe renal dysfunction defined as a KDIGO (Kidney Disease Improving Global Outcomes) score ≥3 vs <3. | Day 4 | 
| Analysis of the primary endpoint in relation with patient severity | Analysis of the primary endpoint in relation withpatient severity according to SAPS 2 (Simplified Acute Physiology Score) score: <15, 15-30, >30 | Day 4 | 
| Mortality | Patient deceased: yes or no | Day 28 | 
| Number of days alive without failure at Day 28 | Number of days without failure | Day 28 | 
| Time to normalization of lactatemia (<2 mmol/l) | Represents time from randomization to first lactatemia <2 mmol/l in hours | Day 4 | 
| Fluid balance in L | The fluid balance will be deduced from the daily weight changes in kilograms, the density of water being equal to 1 | Day 4 | 
| Therapeutic adjustments including bolus vascular filling, changes in vasopressor flow, and administration of diuretics | Number of therapeutic adjustments | Day 4 | 
| Length of stay in ICU (ready for discharge) | Length of stay in ICU from randomization to discharge in days | Day 28 | 
| Length of stay in hospital | Number | Day 28 | 
| Adverse effects | Number and type of adverse events | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monitoring, Transthoracic Echocardiography, Blood Volume, Fluid management