Blood Volume Assessment in COVID-19 and Bacterial Sepsis (BVAC19)

Blood Volume, Components and Capillary Leak in ICU Patients With SARS-CoV-2 and Bacterial Infections

In patients with SARS-CoV-2 or bacterial infection admitted to the intensive care unit (ICU), the state of the intravascular volume, the characteristics of the blood volume components, and the development of a vascular leak is currently unknown. The relationship of these parameters with parameters of cardiac performance, lung edema and sublingual microcirculatory perfusion parameters have never been studied.

Study Overview

• Status: Completed
• Conditions: Covid19; Bacterial Infections; Acute Respiratory Distress Syndrome; Bacterial Sepsis
• Intervention / Treatment: Device: BVA-100; Device: Transpulmonary Thermodilution (TPTD); Device: Sublingual Microcirculation

Detailed Description

Acute respiratory failure related to infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is the main reason for ICU admission in in the majority of patients admitted to the ICU in this viral syndrome, and it presents a significant clinical challenge. Severe hypoxemia in these patients is thought to be related in part to generation of alveolar edema. This would be related to the specific infection related injury of the alveoli-capillary membrane, however other factors could be related to edema formation. Although patients meet criteria for the Acute Respiratory Distress Syndrome (ARDS), there is significant controversy about whether the lungs of the COVID-19 patients have the characteristics of ARDS and thus whether the treatment should mimic treatment of ARDS due to other causes. A general principle in ARDS patients is to avoid positive fluid balances as this may contribute to alveolar edema. Also, the guidelines on the management of COVID-19 patients by the Society of Critical Care Medicine advocate a conservative fluid strategy. However, uncorrected hypovolemia may result in additional organ dysfunction (especially kidney injury). The clinical fluid status is usually estimated by the presence of peripheral edema and daily fluid balances and thus prone to errors as these are poorly related to the circulating blood volume. Management of patients with sepsis based on blood volume measurements and red blood cell volume, to disclose true anemia, has been shown to improve outcome. Finally, the transudation of albumin in the extravascular space has been shown to be associated with outcome of critically ill patients. It is highly plausible that these parameters could help guide the care of COVID-19 patients given the available data in the literature, thus promoting better treatment of these patients.

This is a prospective multicenter study where the treatment team is blinded to the results of the study. The primary objective of the study is to describe the blood volume, the volume of blood components, the capillary leak and parameters of cardiac performance, lung edema and sublingual microcirculatory perfusion and their trajectory during the early phase of hospitalization of patients with SARS-CoV-2 or bacterial infection.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

• Study Contact: Name: Jan Bakker, MD, PhD; Phone Number: 718-630-7000; Email: Jan.Bakker@nyulangone.org

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Uniformed Services University of the Health Sciences
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the ICU with a confirmed SARS-CoV-2 infection or bacterial infection

Description

Inclusion Criteria:

• Confirmed SARS-CoV-2 or bacterial infection
• Patient admitted to the ICU
• Patient age is between 18 and 95 years
• Patent peripheral or central venous line from which blood draws can be made and through which the 131I bolus can be administered
• Arterial catheter considered indicated by primary team caring for the patient

Exclusion Criteria:

• Refused informed consent to participate in the study
• Pregnant or possible pregnant women
• Patient unlikely to survive more than 72h
• Patient with life sustaining treatment limitations (use of renal replacement therapy)
• Patient already on or likely to be placed on extra-corporeal membrane oxygenation support within 48h after admission
• Known allergy to iodine or iodinated 131I albumin
• Patients with chronic renal failure requiring renal replacement therapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 ICU Patients; Patients who are admitted to the ICU with a confirmed SARS-CoV-2 infection	Device: BVA-100; The BVA-100 is a software package designed to calculate human blood volume using the method of tracer dilution. It uses tagged serum albumin.; Device: Transpulmonary Thermodilution (TPTD); TPTD consists of placing a thermistor-equipped catheter in a central artery (usually the femoral or axillary artery) and injecting cold saline solution into a central vein through a central venous catheter.; Other Names: PICCO; Device: Sublingual Microcirculation; With incident dark field imaging, the CytoCam device can record digital image sequences using a handheld camera. In the current study the camera will be used to non-invasively record images of the sublingual microcirculation.; Other Names: CytoCam
ICU Patients with bacterial infection; Patients who are admitted to the ICU with a confirmed bacterial infection. Bacterial infection is defined as the clinical suspicion of a bacterial infection with the presence of two or more clinical markers of infection: abnormal body temperature (>38C or <36C); increased heart rate (>90 b/min),; increased respiratory rate > 20/min or a decreased arterial CO2: PaCO2 < 32 mmHg; Abnormal white blood cell count: < 4000 mm3 or > 12,000 /mm3 or > 10% immature cells OR; The presence of a positive (blood) culture with bacterial growth.	Device: BVA-100; The BVA-100 is a software package designed to calculate human blood volume using the method of tracer dilution. It uses tagged serum albumin.; Device: Transpulmonary Thermodilution (TPTD); TPTD consists of placing a thermistor-equipped catheter in a central artery (usually the femoral or axillary artery) and injecting cold saline solution into a central vein through a central venous catheter.; Other Names: PICCO; Device: Sublingual Microcirculation; With incident dark field imaging, the CytoCam device can record digital image sequences using a handheld camera. In the current study the camera will be used to non-invasively record images of the sublingual microcirculation.; Other Names: CytoCam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Absolute Total Blood Volume	Absolute total blood volume calculated using BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Total Blood Volume Relative to Ideal Body Weight	Total blood volume relative to ideal body weight calculated using the BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Absolute Red Blood Cell Volume	Absolute red blood cell volume calculated using the BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Red Blood Cell Volume Relative to Ideal Body Weight	Red blood cell volume relative to ideal body weight calculated using the BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Absolute Plasma Volume	Absolute plasma volume calculated using the BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Plasma Volume Relative to Ideal Body Weight	Plasma volume relative to ideal body weight calculated using the BVA-100 software.	Day 1, Day of ICU Discharge (up to day 21)
Change in Transudation Rate of Albumin	Transudation rate of albumin calculated using the BVA-100 software. An increase indicates the transudation rate increased during the observational period.	Day 1, Day of ICU Discharge (up to day 21)
Change in Heart Rate	Measured using PICCO. Heart rate expressed as beats per minute (BPM).	Day 1, Day of ICU Discharge (up to day 21)
Change in Cardiac Output	Measured using PICCO. Cardiac output expressed in liters per minute (L/min).	Day 1, Day of ICU Discharge (up to day 21)
Change in Stroke Volume	Measured using PICCO. Stroke volume expressed in milliliters per square meter (mL/m2).	Day 1, Day of ICU Discharge (up to day 21)
Change in Systemic Vascular Resistance (SVR)	Measured using PICCO. SVR expressed in dynes/second/cm^5.	Day 1, Day of ICU Discharge (up to day 21)
Change in Global End Diastolic Volume (GEDV) Index	Measured using PICCO. GEDV expressed in mL/m2.	Day 1, Day of ICU Discharge (up to day 21)
Change in Intra-Thoracic Blood Volume Index (ITBVI)	Measured using PICCO. ITBVI expressed in mL/m2.	Day 1, Day of ICU Discharge (up to day 21)
Change in Extravascular Lung Water (EVLW)	Measured using PICCO. EVLW expressed in mL/kg.	Day 1, Day of ICU Discharge (up to day 21)
Maximum Stroke Volume	Measured using PICCO. Stroke volume expressed in mL/m2.	Up to Day of ICU Discharge (up to day 21)
Minimum Stroke Volume	Measured using PICCO. Stroke volume expressed in mL/m2.	Up to Day of ICU Discharge (up to day 21)
Maximum Pulse Pressure	Measured using PICCO. Pulse pressure expressed in millimeters of mercury (mmHg).	Up to Day of ICU Discharge (up to day 21)
Minimum Pulse Pressure	Measured using PICCO. Pulse pressure expressed in millimeters of mercury (mmHg).	Up to Day of ICU Discharge (up to day 21)
Change in Systolic Blood Pressure	Measured using PICCO. Systolic blood pressure expressed in mmHg.	Day 1, Day of ICU Discharge (up to day 21)
Change in Diastolic Blood Pressure	Measured using PICCO. Diastolic blood pressure expressed in mmHg.	Day 1, Day of ICU Discharge (up to day 21)
Mean Blood Pressure	Measured using PICCO. Blood pressure expressed in mmHg.	Up to Day of ICU Discharge (up to day 21)
Change in Central Venous Pressure (CVP)	Measured using PICCO. CVP expressed in mmHg.	Day 1, Day of ICU Discharge (up to day 21)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with New Onset Renal Injury	Up to Day of ICU Discharge (up to day 21)
Number of Participants Requiring Renal Replacement Therapy	Up to Day of ICU Discharge (up to day 21)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Daxor Corporation
• Investigators: Principal Investigator: Jan Bakker, MD, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): April 9, 2023
• Study Completion (Actual): April 9, 2023

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Bacterial Infections and Mycoses; Lung Injury; Infant, Premature, Diseases; COVID-19; Sepsis; Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Bacterial Infections
• Other Study ID Numbers: 20-00896

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes