Plasma Volume in Healthy Reproductive Age Women Using Indocyanine Green Dye
Authors: Aguree Sixtus , Gernand Alison D. 
Published: November 2023

The volume of circulating plasma may impact interpretation of nutritional biomarker concentrations measured in blood, and while we continue to improve biomarkers related to health and expand their use, little attention has been given to plasma volume. Methods for plasma volume measurement have been expensive and cumbersome, among other barriers, and have been used for assessment mainly in disease states rather than in healthy populations. Indocyanine green (ICG) dye has been used as a safe method for repeated measurements of plasma volume, with techniques available to reduce cost and burden. Our objective was to pilot a simple, quick method for plasma volume measurement using ICG dye in healthy women of reproductive age and to assess the relationship between plasma volume and markers of body composition and nutritional status.Participants were a convenience sample of women with a regular menstrual cycle who responded to announcements at Penn State University. Eligible women participated in one visit after an overnight fast in which demographic and health data were self‐reported and weight, height, blood pressure, and body fat composition were measured (n=8). For plasma volume measurement, subjects rested for 15 minutes in a supine position, an IV was placed and blood samples were taken for nutritional biomarkers, and a bolus injection of ICG (0.25 mg/kg) was given over 5 seconds and flushed with 10 mL saline. Then 5 blood samples were collected from the same arm every 45 seconds (from 2 to 5 minutes after the ICG injection). ICG concentration was measured in each sample using a spectrophotometer, then a disappearance curve was fitted to extrapolate back to the concentration at injection.Women had a mean (SD) age of 24.3 (4.1) years, BMI of 23.8 (2.9) kg/m2, and body fat percentage of 28.5 (5.3) %. Women were mostly white, single, and nulliparous. Hemoglobin and hematocrit were 12.3 (0.7) g/dL and 37.1 (2.3) %, respectively. Plasma volume was highly correlated with body weight (r=0.86, p=0.006), fat mass (r=0.79, p=0.020), body fat percentage (r=0.72, p=0.045), lean body mass (r=0.84, p=0.009), and body surface area (r=0.89, p=0.003). Plasma volume was not associated with height (r=0.47, p=0.238), BMI (r=0.68, p=0.064), hemoglobin (r=0.11, p=0.803), or hematocrit (r=0.17, p=0.686). Plasma volume was neither associated with systolic blood pressure (r=0.27, p=0.525) nor diastolic blood pressure (r=0.60, p=0.118). The mean plasma volume was 2000 (400) mL or 31.0 (3.6) mL/kg by body weight, and 1152 (173) mL/m2 by body surface area.Plasma volume was positively associated with body weight and body composition, as well as body surface area. Contrary to research suggesting BMI as a potential proxy measure for plasma volume, we did not find an association between plasma volume and BMI, nor other key indicators of nutritional status and health. While these findings are preliminary, we have successfully implemented a relatively simple method for measuring plasma volume in healthy women of reproductive age. Plasma volume should be measured in future studies to assess its relationship with health outcomes and potential impact on interpretation of plasma‐based biomarkers.Support or Funding InformationInternal Penn State funds