Persistent inflammation and anemia among critically ill septic patients

BACKGROUND: Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume. METHODS: Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate Delta Hb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted Delta Hb (Adj Delta Hb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with Adj Delta Hb of greater than 0 (positive Adj Delta Hb, n = 18) were compared with patients with Adj Delta Hb of less than or equal to 0 (negative Adj Delta Hb, n = 24). RESULTS: Plasma tumor necrosis factor a, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative Adj Delta Hb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colonystimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower Adj Delta Hb was associatedwith higher day 14 levels of IL-6 (r(2) = 0.22, p < 0.01), IL-8 (r(2) = 0.10, p = 0.04), stromal cell-derived factor 1 (r(2) = 0.14, p = 0.02), and tumor necrosis factor a (r(2) = 0.13, p = 0.02), but not EPO. Patients with negative Adj Delta Hb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels. CONCLUSION: Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO. Copyright (c) 2018 Wolters Kluwer Health, Inc. All rights reserved.