De-resuscitation Informed by Ultrasound for Patients With Sepsis

Study Overview
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Brief Summary
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Randomized, unblinded clinical trial of 152 critically ill patients with sepsis admitted to the intensive care unit. The primary determine if using the Venous Excess Ultrasound Score (VExUS) to guide fluid deresuscitation in critically ill patients with sepsis reduces net fluid balance at 5 days as compared to usual care.

Detailed Description
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Physicians can assess venous congestions with point of care ultrasound of intraabdominal veins using the venous excess in ultrasound score (VExUS), which has been shown to predict the harmful effects of volume overload. We seek to determine if VExUS-guided deresuscitation reduces the fluid balance in critically ill patients with sepsis as compared to usual care. This score compiles findings from the inferior vena cava, hepatic vein Doppler waveform, portal vein Doppler waveform, and intrarenal vein Doppler waveform: Grade 0: IVC < 2cm, normal pattern in flow patterns of hepatic, portal, and intrarenal veins Grade 1: IVC ≥ 2cm, normal patterns or mild abnormalities in flow patterns of hepatic, portal, and intrarenal veins. Grade 2: IVC ≥ 2cm, severe venous flow pattern in one among hepatic, portal, and intrarenal veins. Grade 3: IVC ≥ 2cm, severe venous flow pattern in multiple among hepatic, portal, and intrarenal veins. After informed consent, subjects will be randomized in a 1:1 ratio to the VExUS-guided intervention arm vs control arm. Subjects in both arms will undergo daily ultrasound, and the investigator will calculate the VExUS immediately after ultrasounds are obtained.

Official Title
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Optimizing Fluid Management Informed by Ultrasound for Patients With Sepsis

Conditions
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Sepsis, Septic Shock, Sepsis, Severe, Volume Overload

Intervention / Treatment
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* Diagnostic Test: VExUS score


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Must be suspected by the treating physician to have sepsis as the primary cause of their acute illness as exhibited by 2 or more of the following Systemic Inflammatory Response Syndrome (SIRS) criteria: Temperature of > 38 C or < 36 C Heart rate of > 90/min Respiratory rate of > 20/min or PaCO2 < 32 mm Hg White blood cell count > 12000/mm3 or < 4000/mm3 or >10% immature bands. 2. Known or suspected infection at the time of screening 3. Admission to the ICU for <24 hours Since approximately 12% of patients ultimately diagnosed with sepsis do not meet SIRS criteria, SIRS negative patients will be eligible for the study if the treating physician makes a clinical diagnosis of severe sepsis or septic shock. Exclusion Criteria: Patients with conditions that may interfere with portal Doppler assessments such as cirrhosis or portal thrombosis Patients with severe chronic kidney disease (estimated glomerular filtration rate<15 mL/min per 1.73 m2 calculated using the Modified Diet in Renal Disease formula). Age < 18 years Active atrial fibrillation or atrial flutter Hemodynamic instability due to active hemorrhage Acute cerebral vascular event Acute coronary syndrome (excluding elevated troponin thought to be from demand ischemia) Acute pulmonary edema Status asthmaticus Drug overdose Injury from burn or trauma Status epilepticus Indication for immediate surgery Received CPR within 24 hours of enrollment Pregnancy Incarceration.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, unblinded clinical trial of 152 critically ill patients with sepsis admitted to the intensive care unit.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VExUS-Guided Arm<br>Will receive 24 hour fluid balance target based on daily VExUS score. | Diagnostic Test: VExUS score<br>* The care team will be informed of the VExUS immediately after the ultrasound is performed and given a suggested target for the following 24 hours as follows: VExUS 0: The patient will likely tolerate more fluid if clinically needed. VExUS 1: The patient has evidence of mild venous congestion. The investigators recommend targeting a net neutral or negative fluid balance with diuresis. VExUS 2-3: The patient has evidence of moderate to severe venous congestion. The investigators recommend targeting a fluid balance of negative 1-2L with diuresis. If the investigator cannot obtain ultrasound images of sufficient quality to calculate VExUS, the care team will be informed that there is no recommendation for that subject on that day.<br>|
| No Intervention: Usual Care Control Arm<br>Treating team will be blinded to results of daily VExUS score and will set 24 hour fluid balance target based on usual care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Fluid Balance at 5 days post ICU discharge or ICU Discharge | Total fluid balance (ins minus outs) | At 5 days post ICU admission or ICU discharge, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute Kidney Injury | acute kidney injury as defined by KDIGO criteria | At 5 days post ICU admission or ICU discharge, whichever comes first | 
| Incidence of respiratory failure | Incidence of respiratory failure defined by intubation rates, ventilator free days, ventilator days, use of non-invasive positive pressure ventilation, and use of high flow oxygen | At 5 days post ICU admission or ICU discharge, whichever comes first | 
| Change in SOFA score | Change in Sequential Organ Failure Assessment (SOFA) score during study period, on scale of 0-48, with higher values being a worse outcome | At 5 days post ICU admission or ICU discharge, whichever comes first | 
| 28-day and in-hospital mortality | All-cause mortality. | 28 days and during hospital admission up to 24 weeks | 
| ICU discharge fluid balance | Cumulative admission fluid balance at time of ICU discharge. | From ICU admission to ICU discharge or 30 days after ICU admission, whichever comes first | 
| Daily Sonographic B Line Measurement | Measured by counting sonographic B lines in 16 lung zones | study enrollment to ICU discharge or 5 days post-enrollment, whichever comes first |