1. Blood Volume Analysis Can Distinguish True Anemia from Hemodilution in Critically Ill Trauma Patients PY Van, MD ∙ SD Cho, MD ∙ SJ Underwood, MS GJ Hamilton, BS ∙ LB Ham, MD ∙ MA Schreiber, MD

2. Background Hemorrhage leading cause of preventable death in trauma victims Decreased peripheral hematocrit (pHct) used as marker for blood loss pHct may not represent true red blood cell volume (RBCV)

3. Background

4. Surrogate measures to deduce volume status – Vital signs and physical exam – Laboratory tests – Invasive monitoring Experienced clinicians frequently wrong – 51% concordance with blood volume analysis Androne, AS et al. Am J Cardiol 2004

5. Blood Volume Analysis Indicator dilution principle – Known quantity of tracer injected into unknown volume (intravascular space) – After equilibration of tracer, plasma sampled Concentration of tracer in sample is measured Unknown volume is inversely proportional to concentration of tracer in the sample volume Larger the unknown volume, more dilute the tracer

6. Concentration of tracer injected Volume of sample withdrawn Conc. tracer in sample withdrawn Unknown volume (plasma volume) Indicator Dilution Principle C1C1 V1V1 C2C2 V2V2 =

7. Blood Volume Analysis Single injection radiolabeled 131 I-albumin. Serial blood samples drawn over 40 minutes Analysis yields actual and ideal TBV, RBCV, PV

8. Blood Volume Analysis pHct RBCV = + PV TBV = RBCV + PV

9. Blood Volume Analysis Normalized hematocrit (nHct) – pHct is adjusted for volume derangement: nHct = pHct x Measured TBV Ideal TBV

10. Blood Volume Analysis Ideal volumes determination – Based on math model from Metropolitan Life height and weight tables ( > 100,000 data points) – Blood volume dependent on body composition Weight and body surface areas alone not adequate Lean vs fat tissue proportions Feldschuh J et al. Circulation. 1977

11. Hypothesis Use of pHct alone in critically ill trauma patients will result in over-diagnosis of anemia

12. Methods Trauma ICU pts recruited 24hrs post admission Baseline blood sample Injection of 1mL 25 µCi of 131 I-albumin 12 minute equilibration period – Then 5 serial blood draws, 6 minutes apart Samples processed on BVA-100 Blood Volume Analyzer (Daxor Corporation, NY, NY)

13. Methods Measured volumes compared to ideal -- percent deviation from ideal calculated

14. Methods Pts stratified into 3 groups based on deviation from ideal total blood volume – Hypovolemic: > 8% deficit relative to ideal – Normovolemic: < 8% variation relative to ideal – Hypervolemic: > 8% excess relative to ideal

15. Characteristics Patients (n = 27) Male / Female13 / 14 Age49.6 ± 3.8 Body Mass Index29.3 ± 6.2 APACHE II17.9 ± 1.5 Injury Severity Score29.8 ± 2.5 All values are mean ± standard deviation

16. Results

17. Volume Status and Fluids Hypovolemic (n = 12) Normovolemic (n =19) Hypervolemic (n = 33) Fluid In (mL) 17,881 (10065, 41396) 30,306 (14752, 52026) 22,016 (18100, 33397) Net Fluid (mL) 13,579 (4702, 18708) 2,799 (1969, 15861) 11,807 (6924, 17373) All values are medians (interquartile range) All p = NS, Mann-Whitney U test No significant difference in volume of fluids given or net fluid balance between each volume status

18. Results No linear correlation between net fluid balance and changes in TBV, RBCV, and PV between each analysis Moderate linear correlation between pHct and RBCV (R 2 = 0.3)

19. Results No differences in ISS when compared across the volume status groups No correlation between ISS and rate of albumin transudation

20. pHct versus nHct pHctnHctDifferencepHct < 30nHct < 30 Overdiagnosis of anemia Hypovolemic (n=12) 26.120.9* 5.2 ± 3.3 91.7% (11) -- Normovolemic (n=20) 27.1 0.0 ± 1.2 80.0% (16) -- Hypervolemic (n=33) 26.532.9* -6.4 ± 4.4 81.8% (27) †27.3% (9) 54.5% (18) All (n=65) 26.628.9 -2.3 ± 5.7 83.1% (54) 55.4% (36) 27.7% (18) Paired t-test * p < 0.05 Chi-squared † p < 0.05

21. Conclusions Assessing volume status is challenging No differences in amount of fluids administered to volume status groups pHct compared to nHct – Overestimates anemia in hypervolemic pts – Underestimates anemia in hypovolemic pts

22. Limitations Preliminary study -- small number of patients BVA not a dynamic test – snapshot in time Assume RBCV constant during testing – Not reasonable if bleeding > 100mL/hr Availability of tracer and personnel

23. Future Directions Further characterize effects of fluid and blood product administration on volume status Blood volume analysis upon ICU admission – Establish baseline – Initiate therapies based on blood volumes – Avoid unnecessary CT scans and transfusion when BVA shows low pHct due to hemodilution

24. Acknowledgements Martin Schreiber, MD S David Cho, MD Samantha Underwood, MS Richard Loftus, Daxor Corporation OHSU Nuclear Medicine

26. Blood Volume Analysis