De-resuscitation Informed by Ultrasound for Patients With Sepsis

Not Applicable

• Conditions: Volume Overload; Sepsis; Septic Shock; Sepsis, Severe
• Interventions: Diagnostic Test: VExUS score

• Registration Number: NCT04921319
• Lead Sponsor: The Miriam Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-03
• Study First Submitted: 2021-04-07
• Study Start: 2021-04-26
• Study First Submitted QC: 2021-06-02
• Last Update Submitted: 2021-06-02
• Study First Posted: 2021-06-10
• Last Update Posted: 2021-06-10
• Primary Completion: 2022-06-30
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 152

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:

  2. Temperature of > 38 C or < 36 C

  3. Heart rate of > 90/min

  4. Respiratory rate of > 20/min or PaCO2 < 32 mm Hg

  5. 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

1. Patients with conditions that may interfere with portal Doppler assessments such as cirrhosis or portal thrombosis
2. 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).
3. Age < 18 years
4. Active atrial fibrillation or atrial flutter
5. Hemodynamic instability due to active hemorrhage
6. Acute cerebral vascular event
7. Acute coronary syndrome (excluding elevated troponin thought to be from demand ischemia)
8. Acute pulmonary edema
9. Status asthmaticus
10. Drug overdose
11. Injury from burn or trauma
12. Status epilepticus
13. Indication for immediate surgery
14. Received CPR within 24 hours of enrollment
15. Pregnancy
16. Incarceration.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VExUS-Guided Arm	VExUS score	Will receive 24 hour fluid balance target based on daily VExUS score.

Primary Outcome Measures

Name	Time	Method
Cumulative Fluid Balance at 5 days post ICU discharge or ICU Discharge	At 5 days post ICU admission or ICU discharge, whichever comes first	Total fluid balance (ins minus outs)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States