Brandtner Anna, Tymoszuk Piotr, Nairz Manfred, Lehner Georg F, Fritsche Gernot, Vales Anja, Falkner Andreas, Schennach Harald, Theurl Igor, Joannidis Michael, Weiss Günter, Pfeifhofer-Obermair Christa
Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.
Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria.
J Intensive Care. 2020 Oct 1;8:76. doi: 10.1186/s40560-020-00495-8. eCollection 2020.
Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body's iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis.
Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects.
Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA-TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients.
Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score.
The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).
脓毒症是感染后宿主反应失调，与大量免疫激活和高死亡率相关。仍需进一步明确预测临床病程的风险因素和实验室参数。铁代谢受机体铁状态和免疫反应两者调节。铁本身不仅是红细胞生成所必需的，也是许多细胞和代谢功能所必需的。此外，铁的可利用性在感染中是一个关键决定因素，因为它是大多数微生物的必需营养素，但也会影响免疫功能和血管内氧化应激。在此，我们采用前瞻性研究设计来调查血清铁参数对脓毒症预后的潜在影响。
在一家医疗重症监护病房（ICU）中，对61例符合Sepsis-3标准的脓毒症患者（37例男性，24例女性）的前瞻性队列进行铁代谢血清标志物检测，并比较幸存者和非幸存者之间的差异。通过对性别和年龄效应进行校正的线性和逻辑回归，研究按感染部位和联合用药分层的患者中铁参数的调节情况，以及这些标志物与脓毒症严重程度评分和生存率的相关性。
观察到ICU入院时血清铁和铁蛋白浓度升高与器官衰竭严重程度（序贯器官衰竭评估[SOFA]评分）及死亡率呈正相关。此外，高转铁蛋白饱和度（TF-Sat）、升高的铁蛋白和血清铁水平以及低转铁蛋白浓度与生存率降低相关。由SOFA和转铁蛋白饱和度（SOFA-TF-Sat）组成的逻辑回归模型对脓毒症ICU患者的生存具有最佳预测能力。值得注意的是，ICU入院前输血导致脓毒症患者TF-Sat升高和生存率降低。
我们的研究表明血清铁参数对脓毒症预后有重要影响。此外，我们确定转铁蛋白饱和度是脓毒症生存的独立预测指标，也是铁代谢参数，在联合模型中可能会提高SOFA评分的预测能力。
本研究按照《赫尔辛基宣言》关于生物医学研究的建议进行。该研究获得了因斯布鲁克医科大学机构伦理审查委员会的批准（研究编号AN2013-0006）。
