From the Sepsis and Critical Illness Research Center (T.J.L., J.C.M., J.A.S., T.O.-B., G.L.G., Z.W., B.A.B., R.F.U., A.B., C.L., F.A.M., L.L.M., S.C.B., P.A.E., A.M.M.); Department of Surgery (T.J.L., J.C.M., J.A.S., F.A.M., L.L.M., S.C.B., P.A.E., A.M.M.); Department of Anesthesiology (T.O.-B., A.B.); Department of Biostatistics (G.L.G., Z.W., B.A.B.); Department of Medicine (C.L.); and Institute on Aging (C.L.), University of Florida Health, Gainesville, Florida.
J Trauma Acute Care Surg. 2019 Feb;86(2):260-267. doi: 10.1097/TA.0000000000002147.
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.
Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with AdjΔHb of greater than 0 (positive AdjΔHb, n = 18) were compared with patients with AdjΔHb of less than or equal to 0 (negative AdjΔHb, n = 24).
Plasma tumor necrosis factor α, 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 AdjΔHb 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 colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r = 0.22, p < 0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor α (r = 0.13, p = 0.02), but not EPO. Patients with negative AdjΔHb 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.
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.
Prognostic study, level II.
在危重病脓毒症患者中，炎症细胞因子、促红细胞生成素（EPO）和贫血之间的关系仍不清楚。本研究假设炎症细胞因子升高和 EPO 降低与铁限制性贫血有关，同时考虑手术失血量、采血损失量和红细胞（RBC）输注量，对此进行了检验。
对 42 例危重病脓毒症患者进行前瞻性观察队列研究。用脓毒症发病时和出院时的血红蛋白（Hb）计算 ΔHb。用手术失血量、采血损失量和 RBC 输注量计算校正 ΔHb（AdjΔHb），假设 300 mL RBC 等于 1 g/dL Hb。将 AdjΔHb 大于 0（阳性 AdjΔHb，n = 18）的患者与 AdjΔHb 小于或等于 0（阴性 AdjΔHb，n = 24）的患者进行比较。
在第 0、1、4、7 和 14 天测量患者的血浆肿瘤坏死因子-α、粒细胞集落刺激因子、白细胞介素（IL）-6、IL-8、EPO、红细胞平均体积和血清转铁蛋白受体。与阴性 AdjΔHb 患者相比，第 14 天的 IL-6（37.4 与 15.2 pg/mL，p < 0.05）、IL-8（39.1 与 18.2 pg/mL，p = 0.01）和粒细胞集落刺激因子（101.3 与 60.5 pg/mL，p = 0.01）水平显著更高，但 EPO 水平无显著差异。线性回归分析显示，较低的 AdjΔHb 与第 14 天较高的 IL-6（r = 0.22，p < 0.01）、IL-8（r = 0.10，p = 0.04）、基质细胞衍生因子 1（r = 0.14，p = 0.02）和肿瘤坏死因子-α（r = 0.13，p = 0.02）水平相关，但与 EPO 无关。与阴性 AdjΔHb 患者相比，第 4（89.6 与 93.2 fL/细胞，p = 0.04）、7（92.3 与 94.9 fL/细胞，p = 0.04）和 14 天（92.1 与 96.0 fL/细胞，p = 0.03）的红细胞平均体积显著降低，但血清转铁蛋白受体水平无显著差异。
炎症细胞因子持续升高与危重病脓毒症患者的铁限制性贫血有关，即使不存在系统性铁缺乏，也与内源性 EPO 无关。
预后研究，II 级。
