A novel fluorescent clinical method to rapidly quantify plasma volume

Bruce Molitoris, Anthony G. George, Patrick T. Murray, Daniel Meier, Erinn S. Reilly, Erin Barreto, Ruben M. Sandoval, Dana V. Rizk, Andrew D. Shaw, W. Frank Peacock

Research output: Contribution to journalArticle

Abstract

Objectives: To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods: This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject's hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler's formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results: PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler's estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions: This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration.

Original languageEnglish (US)
Pages (from-to)168-179
Number of pages12
JournalCardioRenal Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

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Plasma Volume
Healthy Volunteers
Blood Volume
Dextrans
Fluorescent Dyes
Albumins
Coloring Agents
Weights and Measures
Rhodamines
Body Surface Area
Fluorescein
Chronic Renal Insufficiency
Hematocrit
Intravenous Injections

Keywords

  • Blood volume
  • Carboxy-methyl dextran
  • Chronic kidney disease
  • Fluorescent indicator technique

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Urology

Cite this

Molitoris, B., George, A. G., Murray, P. T., Meier, D., Reilly, E. S., Barreto, E., ... Peacock, W. F. (2019). A novel fluorescent clinical method to rapidly quantify plasma volume. CardioRenal Medicine, 9(3), 168-179. https://doi.org/10.1159/000496480

A novel fluorescent clinical method to rapidly quantify plasma volume. / Molitoris, Bruce; George, Anthony G.; Murray, Patrick T.; Meier, Daniel; Reilly, Erinn S.; Barreto, Erin; Sandoval, Ruben M.; Rizk, Dana V.; Shaw, Andrew D.; Peacock, W. Frank.

In: CardioRenal Medicine, Vol. 9, No. 3, 01.03.2019, p. 168-179.

Research output: Contribution to journalArticle

Molitoris, B, George, AG, Murray, PT, Meier, D, Reilly, ES, Barreto, E, Sandoval, RM, Rizk, DV, Shaw, AD & Peacock, WF 2019, 'A novel fluorescent clinical method to rapidly quantify plasma volume', CardioRenal Medicine, vol. 9, no. 3, pp. 168-179. https://doi.org/10.1159/000496480
Molitoris B, George AG, Murray PT, Meier D, Reilly ES, Barreto E et al. A novel fluorescent clinical method to rapidly quantify plasma volume. CardioRenal Medicine. 2019 Mar 1;9(3):168-179. https://doi.org/10.1159/000496480
Molitoris, Bruce ; George, Anthony G. ; Murray, Patrick T. ; Meier, Daniel ; Reilly, Erinn S. ; Barreto, Erin ; Sandoval, Ruben M. ; Rizk, Dana V. ; Shaw, Andrew D. ; Peacock, W. Frank. / A novel fluorescent clinical method to rapidly quantify plasma volume. In: CardioRenal Medicine. 2019 ; Vol. 9, No. 3. pp. 168-179.
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AU - Barreto, Erin

AU - Sandoval, Ruben M.

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N2 - Objectives: To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods: This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject's hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler's formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results: PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler's estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions: This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration.

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