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Pilot Validation of a Hemodilution Technique to Estimate Blood Volume in Vivo

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03031600
Recruitment Status : Unknown
Verified January 2017 by Uniformed Services University of the Health Sciences.
Recruitment status was:  Not yet recruiting
First Posted : January 25, 2017
Last Update Posted : January 26, 2017
Sponsor:
Collaborators:
Duke University
Henry M. Jackson Foundation for the Advancement of Military Medicine
Information provided by (Responsible Party):
Uniformed Services University of the Health Sciences

Brief Summary:
The objective of this study is to determine the accuracy of estimating patient blood volume using field-expedient point-of-care measurement of hematocrit before and after hemodilution with a standardized volume of intravenous solution, in comparison to determining patient blood volume by radiodilution. A total of 33 healthy adult male subjects aged 18-35 years will undergo determination of blood volume in a fixed order: first by radiodilution, then by hemodilution. Blood volume as measured by radiodilution will be correlated with blood volume as estimated with hemodilution to assess the potential validity of hemodilution as means of estimating blood volume.

Condition or disease Intervention/treatment Phase
Hypovolemia Hypervolemia Diagnostic Test: Radiodilution via Daxor BVA-100 Diagnostic Test: Hemodilution via hematocrit measurement Not Applicable

Detailed Description:

The primary goal of perioperative fluid therapy is to optimize patient blood volume for a given degree of cardiac function and thereby promote adequate end organ tissue perfusion. In the ideal situation, a surgical patient would maintain a euvolemic total blood volume (TBV) that promotes optimal tissue oxygenation, nutrient supply, and removal of metabolic waste products. Current methods to assess perioperative TBV and manage intravenous (IV) fluids, which include fluid algorithms, physiologic parameters, blood studies, and clinician intuition, are either inaccurate or require highly specialized equipment and training. Therefore, clinicians are faced with the formidable task of attempting to titrate IV fluids with the goal of preserving optimal tissue perfusion in the perioperative period without knowledge of the patient's actual TBV. This long standing clinical conundrum, and the potential iatrogenic consequences of hypo- or hypervolemia, has recently produced a significant degree of inquiry into direct and indirect methods to evaluate cardiac output as a product of fluctuating TBV. The goal of much of this investigation is to generate an evidence-based methodology for administration of perioperative IV fluids to promote euvolemia and preserve adequate tissue perfusion. There is strong evidence from the civilian anesthesia and surgical literature that the use of various indicators of cardiac output as a marker of TBV and a guide for fluid therapy, so called Goal Directed Fluid Therapy (GDFT), leads to significantly better perioperative patient outcomes. However, current GDFT management protocols rely heavily on technology not readily available within or sufficiently ruggedized for use in the military field setting where ongoing accurate estimation of TBV to guide fluid replacement in the presence of major trauma, and its physiologic aftermath, may be critical to survival. Therefore, the primary objective of this study is to assess the accuracy of determining patient TBV using measurement of red blood cell volume (hematocrit, or HCT) with a point-of-care testing device relevant to the military setting, before and after hemodilution with a standard IV solution. The specific aims of the proposed research are to:

  1. Determine subject total blood volume using the gold standard DAXOR Blood Volume Analyzer-100 Analysis System (Radiotracer Dilution Technique).
  2. Compute estimated subject total blood volume using venous blood hematocrit values drawn before and after an intravenous fluid bolus (Hemodilution Technique).
  3. Correlate inter-subject radiotracer dilution technique-derived total blood volume with hemodilution technique-derived total blood volume.

Hypothesis:

The calculated total blood volume derived by a simple clinically applicable hemodilution technique will highly correlate with the gold standard laboratory radiotracer dilution technique.

The proposed study will examine the utility of a simple, clinically applicable, and adaptable method to assess a patient's TBV that does not rely on sophisticated, technology-dependent, direct or indirect measures of cardiac output. Development and confirmation of the accuracy of a simple method to intermittently determine a patient's TBV in the perioperative setting would revolutionize the ability of a practitioner to match perioperative IV fluid administration to the goal of optimizing cardiac output and tissue perfusion. The tremendous potential positive impact of this work on surgical and anesthesia care in both the military and civilian settings is evident in the brief but expansive existing work demonstrating significant improvement in patient outcomes using GDFT techniques. The proposed study is potentially the first step in a future program of research to bring the benefits of GDFT into austere settings.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This study will use a prospective validation design. In this design, each subject will experience both estimation methods/arms (radiodilution and hematocrit dilution) in a fixed sequence. The fixed order is necessary, as hematocrit dilution would bias the results of radiodilution by iatrogenically increasing plasma volume as part of the estimation process.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Pilot Validation of a Hemodilution Technique to Estimate Blood Volume in Vivo
Estimated Study Start Date : May 1, 2017
Estimated Primary Completion Date : May 31, 2018
Estimated Study Completion Date : June 30, 2018

Arm Intervention/treatment
Active Comparator: Radiodilution via Daxor BVA-100
In study arm 1, actual blood volume will be measured using the Daxor Blood Volume Analyzer-100 (BVA-100). In this technique, the subject is injected with 1 ml of human serum albumin labeled with iodine131 (25 microcuries). A small amount of blood is collected from the subject just before injection and at 12, 18, 24, 30, and 36 min after injection.
Diagnostic Test: Radiodilution via Daxor BVA-100
The BVA-100 measures the hematocrit and residual plasma radioactivity of each sample in a semi-automated process, and the residual radioactivity is compared from that of the pre-injection sample to determine plasma volume. The plasma volume and BVA-100-measured hematocrit are then used to calculate the red cell volume and actual blood volume. The BVA-100 is FDA approved for blood volume measurement in vivo, has a reported precision of ± 2.5%, and has demonstrated accuracy and specificity in blood volume assessment in clinical and research settings (Van, P.Y., et al., 2011, Borovka, M., et al., 2013).

Experimental: Hemodilution via hematocrit measurement
In study arm 2, estimated blood volume will measured via hemodilution. . A blood sample (5 ml) will be drawn for baseline determination of hematocrit via iSTAT and lab measurement from the non-dominant arm. After the baseline hematocrit blood sample is drawn, a volume of normal saline equivalent to 10% of the subject's ideal blood volume will be administered over a 12-minute period through the dominant arm IV catheter. Twelve minutes after the infusion is complete, a second blood sample (5 ml) will be drawn from the non-dominant arm for determination of post-bolus hematocrit via iSTAT and lab. Subjects will then be asked to void into a urinal, and urine output will be measured in ml.
Diagnostic Test: Hemodilution via hematocrit measurement
Hemodilution uses the ideal blood volume and serial hematocrit measures drawn before and after administration of a known quantity of IV fluid to estimate blood volume. Ideal blood volume is calculated using the methods described by Feldschuh and colleagues (Feldschuh, J. and Y. Enson, 1977; Feldschuh, J. and S. Katz, 2007). Hematocrit is measured using the Abbot iSTAT point of care testing device and the lab. Urine output is measured in ml. The ideal blood volume, pre and post-bolus hematocrit, fluid bolus volume, and urine output will be used to calculate estimated blood volume using a mathematical model previously described by the investigators (D'Angelo, M., et al., 2015).




Primary Outcome Measures :
  1. Agreement between actual and estimated blood volume [ Time Frame: Actual blood volume is calculated at 36 minutes after start, and estimated blood volume is computed 62 minutes after start. ]
    The primary outcome is the agreement between actual blood volume in ml (as measured via radiodilution by the BVA-100) and estimated blood volume (as measured the methods described in arm 2).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy
  • Normal body mass index (defined as 18.5-24.9 per guidelines issued by the Centers for Disease Control and Prevention)

Exclusion Criteria:

  • Otherwise eligible subjects one or more of the following conditions will be excluded from participation due to the potential to alter blood volume, plasma volume, red cell volume, or microvascular circulation: Cardiovascular disease (to include hypertension, congestive heart failure, previous myocardial infarction, valvular heart disease other than asymptomatic mitral valve prolapse, cardiomyopathy, or peripheral vascular disease), endocrine disease (to include syndrome of inappropriate diuretic hormone, diabetes insipidus, hypothyroidism, hyperthyroidism, or diabetes mellitus), adrenal insufficiency or hypersecretion, renal failure or insufficiency, liver disease, history of sepsis, intravenous fluid administration, nausea, vomiting, diarrhea or heat stress injury within 30 days of the test, eating disorders such as bulimia or anorexia nervosa, or current diuretic or antihypertensive medication use.
  • Additionally, subjects who are allergic to iodine, albumin, or iodinated I131 albumin, or cannot undergo intravenous catheter placement will be ineligible to participate.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03031600


Contacts
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Contact: Kenneth A Wofford, PhD 301-295-1001 kenneth.wofford@usuhs.edu

Sponsors and Collaborators
Uniformed Services University of the Health Sciences
Duke University
Henry M. Jackson Foundation for the Advancement of Military Medicine
Investigators
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Principal Investigator: Kenneth A Wofford, PhD Uniformed Services University of the Health Sciences
Publications:

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Responsible Party: Uniformed Services University of the Health Sciences
ClinicalTrials.gov Identifier: NCT03031600    
Other Study ID Numbers: HU0001-16-1-TS14(N16-P10)
First Posted: January 25, 2017    Key Record Dates
Last Update Posted: January 26, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypovolemia
Pathologic Processes