Background. Early risk stratification in emergency department sepsis management is essential for improving patient outcomes. Fluid resuscitation is a critical intervention, yet it can be associated with adverse effects if not properly managed. Assessing plasma volume status (ePVS) offers a non-invasive method to guide fluid administration. Previous studies have shown that elevated ePVS correlates with poor outcomes in heart failure and myocardial infarction, but its prognostic value in emergency room sepsis remains underexplored.

Objectives. To determine the prognostic significance of ePVS on in-hospital mortality and its associations with mechanical ventilation, vasopressor use, IV fluid resuscitation, and length hospital stay in septic patients at the emergency room.

Methodology. Single center prospective cohort study included 217 patients presented with Sepsis in the Emergency Room. ePVS was calculated using hematocrit and hemoglobin levels at admission. The primary outcome was in-hospital mortality; secondary outcomes included mechanical ventilation, vasopressor use, 24-hour fluid resuscitation, and length of hospital stay. Descriptive statistics, t-tests, Mann-Whitney U tests, Chi-square tests, receiver operating characteristics, logistic and linear regression analyses were used to identify significant associations and adjust confounding factors.

Results. Higher ePVS values were significantly associated with increased in-hospital mortality (OR 1.5, 95% CI 1.15-1.95, p = 0.002) along with increased 24-hour IV fluid resuscitation (OR 1.0004, 95% CI 1.0000-1.0008, p = 0.03). Violin and box plot analyses demonstrated that patients with ePVS ≥ 5.37 had nearly three times the risk of in-hospital mortality compared to those with lower values (HR 2.84, p = 0.0069). ROC analysis revealed moderate predictive accuracy for ePVS (AUC 0.63, p < 0.001). The length of hospital stay was independently correlated with high ePVS (OR 0.97, 95% CI 0.96-0.99, p = 0.002); however, this association lost significance when adjusted for additional variables (p > 0.05). Higher ePVS did not correlate with the use of mechanical ventilation or vasopressor/inotrope use (p > 0.05).

Conclusion. Elevated estimated plasma volume status (ePVS) and increased 24-hour fluid resuscitation are significantly associated with a higher risk of in-hospital mortality, with patients exhibiting elevated ePVS having a threefold increase in mortality risk. ePVS demonstrates moderate predictive accuracy when compared to established risk assessment tools such as APACHE and MSOFA in predicting in-hospital mortality.

Keywords. Sepsis, estimated Plasma Volume Status(ePVS), Fluid Resuscitation, in-hospital mortality, length of hospital stay, use of vasopressors/inotropes

1. M. Singer et al., “The third international consensus definitions for sepsis and septic shock (sepsis-3),” Feb. 23, 2016, American Medical Association. doi: 10.1001/jama.2016.0287.
2. [C. Ince et al., “The endothelium in sepsis,” Mar. 01, 2016, Lippincott Williams and Wilkins. doi: 10.1097/SHK.0000000000000473.
3. Tiru et al., “The Economic and Humanistic Burden of Severe Sepsis,” Pharmacoeconomics, vol. 33, no. 9, pp. 925–937, 2015, doi: 10.1007/s40273-015-0282-y.
4. Fleischmann et al., “Assessment of global incidence and mortality of hospital-treated sepsis current estimates and limitations,” Am J Respir Crit Care Med, vol. 193, no. 3, pp. 259–272, Feb. 2016, doi: 10.1164/rccm.201504-0781OC.
5. Koratala, C. Ronco, and A. Kazory, “Diagnosis of Fluid Overload: From Conventional to Contemporary Concepts,” Nov. 12, 2022, S. Karger AG. doi: 10.1159/000526902.
6. Acheampong and J. L. Vincent, “A positive fluid balance is an independent prognostic factor in patients with sepsis,” Crit Care, vol. 19, no. 1, Jun. 2015, doi: 10.1186/s13054-015-0970-1.
7. Andrews et al., “Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial.,” JAMA, vol. 318, no. 13, pp. 1233–1240, Oct. 2017, doi: 10.1001/jama.2017.10913.
8. P. E. Marik, M. Baram, and B. Vahid, “Does Central Venous Pressure Predict Fluid Responsiveness? *: A Systematic Review of the Literature and the Tale of Seven Mares,” Chest, vol. 134, no. 1, pp. 172–178, Jul. 2008, doi: 10.1378/chest.07-2331.
9. “Goal-Directed Resuscitation for Patients with Early Septic Shock,” New England Journal of Medicine, vol. 371, no. 16, pp. 1496–1506, Oct. 2014, doi: 10.1056/NEJMoa1404380.
10. S. Macdonald, “Fluid Resuscitation in Patients Presenting with Sepsis: Current Insights,” 2022, Dove Medical Press Ltd. doi: 10.2147/OAEM.S363520.
11. “A Randomized Trial of Protocol-Based Care for Early Septic Shock,” New England Journal of Medicine, vol. 370, no. 18, pp. 1683–1693, May 2014, doi: 10.1056/NEJMoa1401602.
12. P. R. Mouncey et al., “Trial of Early, Goal-Directed Resuscitation for Septic Shock,” New England Journal of Medicine, vol. 372, no. 14, pp. 1301–1311, Apr. 2015, doi: 10.1056/nejmoa1500896.
13. Ince et al., “The endothelium in sepsis,” Mar. 01, 2016, Lippincott Williams and Wilkins. doi: 10.1097/SHK.0000000000000473.
14. T. Iba and J. H. Levy, “Derangement of the endothelial glycocalyx in sepsis.,” J Thromb Haemost, vol. 17, no. 2, pp. 283–294, Feb. 2019, doi: 10.1111/jth.14371.
15. K. Duarte, yz Jean-Marie Monnez, yz Eliane Albuisson, yxk Bertram Pitt, F. Zannad, and yyzzxx Patrick Rossignol, “Prognostic Value of Estimated Plasma Volume in Heart Failure,” 2015.
16. J. Chen et al., “Estimated plasma volume status (ePVS) is a predictor for acute myocardial infarction in-hospital mortality: analysis based on MIMIC-III database,” BMC Cardiovasc Disord, vol. 21, no. 1, Dec. 2021, doi: 10.1186/s12872-021-02338-2.
17. K. H. Kim, H. J. Cho, S. C. Kim, and J. Lee, “Prognostic Value of Estimated Plasma Volume Status in Patients With Sepsis,” J Korean Med Sci, vol. 37, no. 18, 2022, doi: 10.3346/jkms.2022.37.e145.
18. [18] G. Turcato, A. Zaboli, S. Sibilio, M. Mian, and F. Brigo, “Estimated plasma volume status can help identify patients with sepsis at risk of death within 30 days in the emergency department,” Emergency Care Journal, vol. 19, no. 4, Dec. 2023, doi: 10.4081/ecj.2023.11655.
19. B. Gao, R. Chen, H. Zhao, H. Zhang, X. Wang, and D. Liu, “Estimated plasma volume status as a simple and accessible predictor of 28-day mortality in septic shock: insights from a retrospective study of the MIMIC-IV database,” Front Med (Lausanne), vol. 11, 2024, doi: 10.3389/fmed.2024.1416396.
20. M. Cecconi, L. Evans, M. Levy, and A. Rhodes, “Sepsis and septic shock,” The Lancet, vol. 392, no. 10141, pp. 75–87, Jul. 2018, doi: 10.1016/S0140-6736(18)30696-2.
21. M. Singer et al., “The third international consensus definitions for sepsis and septic shock (sepsis-3),” Feb. 23, 2016, American Medical Association. doi: 10.1001/jama.2016.0287.
22. S. P. J. Macdonald et al., “Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial,” Intensive Care Med, vol. 44, no. 12, pp. 2070–2078, Dec. 2018, doi: 10.1007/s00134-018-5433-0.
23. L. Evans et al., “Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.,” Intensive Care Med, vol. 47, no. 11, pp. 1181–1247, Nov. 2021, doi: 10.1007/s00134-021-06506-y.
24. J. V. W. A. N. D. A. J. M. A. N. D. E. A. S. Jr., “THE RÔLE OF THE EXTRACELLULAR FLUID IN THE MAINTENANCE OF A NORMAL PLASMA VOLUME,” J Clin Invest, vol. 22, no. 5, pp. 635–641, Sep. 1943, doi: 10.1172/JCI101435.
25. A. Koratala, C. Ronco, and A. Kazory, “Diagnosis of Fluid Overload: From Conventional to Contemporary Concepts,” Cardiorenal Med, vol. 12, no. 4, pp. 141–154, 2022, doi: 10.1159/000526902.
26. M. Fudim and W. L. Miller, “Calculated Estimates of Plasma Volume in Patients With Chronic Heart Failure-Comparison With Measured Volumes.,” J Card Fail, vol. 24, no. 9, pp. 553–560, Sep. 2018, doi: 10.1016/j.cardfail.2018.07.462.
27. G. Turcato, A. Zaboli, L. Ciccariello, and N. Pfeifer, “Estimated plasma volume status (ePVS) could be an easy-to-use clinical tool to determine the risk of sepsis or death in patients with fever,” J Crit Care, vol. 58, pp. 106–112, 2020, doi: https://doi.org/10.1016/j.jcrc.2020.05.001.
28. C. K. Grissom et al., “A modified Sequential Organ Failure Assessment score for critical care triage,” Disaster Med Public Health Prep, vol. 4, no. 4, pp. 277–284, Dec. 2010, doi: 10.1001/dmp.2010.40.
29. R. Kashyap et al., “Current Utility of Sequential Organ Failure Assessment Score: A Literature Review and Future Directions,” Open Respir Med J, vol. 15, no. 1, pp. 1–6, Apr. 2021, doi: 10.2174/1874306402115010001.