Macdonald Stephen P J, Stone Shelley F, Neil Claire L, van Eeden Pauline E, Fatovich Daniel M, Arendts Glenn, Brown Simon G A
Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia; Emergency Department, Armadale Health Service, Perth, Australia.
Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia.
PLoS One. 2014 Oct 24;9(10):e110678. doi: 10.1371/journal.pone.0110678. eCollection 2014.
To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED).
Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups.
Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation.
These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.
在急诊科(ED)中识别可区分严重脓毒症/脓毒性休克与非复杂性脓毒症的生物标志物。
脓毒症患者接受系列血液采样,包括抵达急诊科时以及最初24小时内后续最多三个时间点的采样。使用定量PCR测量外周血白细胞中代表先天免疫反应、器官功能障碍或休克分支的13个基因的信使核糖核酸(mRNA)水平,并与健康对照进行比较。然后在每个时间点测量非复杂性脓毒症和严重脓毒症/脓毒性休克之间差异表达的靶标的血清蛋白浓度,并在两组患者之间进行比较。
27名参与者(中位年龄66岁,四分位间距35, 78)中,10人患有非复杂性脓毒症,17人患有伴有器官衰竭的脓毒症(14人脓毒性休克;3人有其他脓毒症相关器官衰竭)。在急诊科首次采集样本时,严重脓毒症患者中白细胞介素(IL)-10和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的基因表达显著高于非复杂性脓毒症患者。任何靶基因的表达随时间均无显著变化。在急诊科首次采集样本时,严重脓毒症患者中IL-6、IL-8、IL-10、NGAL和抵抗素的血清浓度显著高于非复杂性脓毒症患者,但在就诊后24小时内的所有时间点,与非复杂性脓毒症相比,严重脓毒症中只有IL-8、NGAL和抵抗素一直较高。
这些由受损组织和循环白细胞产生的介质可能在严重脓毒症的发展中起重要作用。进一步的研究将确定除临床风险参数外,它们对于早期识别随后病情恶化和/或死亡风险较高的患者是否具有任何价值。