Molano Franco Daniel, Arevalo-Rodriguez Ingrid, Roqué I Figuls Marta, Montero Oleas Nadia G, Nuvials Xavier, Zamora Javier
Department of Critical Care, Fundacion Universitaria de Ciencias de la Salud, Hospital de San José, Carrera 19 # 8-32, Bogota, Bogota, Colombia, 11001.
Cochrane Database Syst Rev. 2019 Apr 30;4(4):CD011811. doi: 10.1002/14651858.CD011811.pub2.
The definition of sepsis has evolved over time, along with the clinical and scientific knowledge behind it. For years, sepsis was defined as a systemic inflammatory response syndrome (SIRS) in the presence of a documented or suspected infection. At present, sepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Even though sepsis is one of the leading causes of mortality in critically ill patients, and the World Health Organization (WHO) recognizes it as a healthcare priority, it still lacks an accurate diagnostic test. Determining the accuracy of interleukin-6 (IL-6) concentrations in plasma, which is proposed as a new biomarker for the diagnosis of sepsis, might be helpful to provide adequate and timely management of critically ill patients, and thus reduce the morbidity and mortality associated with this condition.
To determine the diagnostic accuracy of plasma interleukin-6 (IL-6) concentration for the diagnosis of bacterial sepsis in critically ill adults.
We searched CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 25 January 2019. We screened references in the included studies to identify additional studies. We did not apply any language restriction to the electronic searches.
We included diagnostic accuracy studies enrolling critically ill adults aged 18 years or older under suspicion of sepsis during their hospitalization, where IL-6 concentrations were evaluated by serological measurement.
Two review authors independently screened the references to identify relevant studies and extracted data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity using the HSROC model parameters. We conducted all analyses in the SAS statistical software package and R software.
We included 23 studies (n = 4192) assessing the accuracy of IL-6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS-2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL-6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above.
AUTHORS' CONCLUSIONS: Our evidence assessment of plasma interleukin-6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin-6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included.
随着脓毒症背后临床和科学知识的发展，其定义也在不断演变。多年来，脓毒症被定义为在有记录或疑似感染的情况下出现的全身炎症反应综合征（SIRS）。目前，脓毒症被定义为由宿主对感染的反应失调导致的危及生命的器官功能障碍。尽管脓毒症是重症患者死亡的主要原因之一，且世界卫生组织（WHO）将其视为医疗保健的优先事项，但它仍缺乏准确的诊断测试。确定血浆中白细胞介素 - 6（IL - 6）浓度的准确性，该指标被提议作为脓毒症诊断的新生物标志物，可能有助于为重症患者提供充分及时的管理，从而降低与此病症相关的发病率和死亡率。
确定血浆白细胞介素 - 6（IL - 6）浓度对成年重症患者细菌性脓毒症诊断的准确性。
我们于2019年1月25日检索了CENTRAL、MEDLINE、Embase、LILACS和Web of Science。我们筛选了纳入研究中的参考文献以识别其他研究。我们对电子检索未设置任何语言限制。
我们纳入了诊断准确性研究，这些研究纳入了18岁及以上在住院期间疑似脓毒症的成年重症患者，其中通过血清学测量评估IL - 6浓度。
两位综述作者独立筛选参考文献以识别相关研究并提取数据。我们使用诊断准确性研究质量评估（QUADAS - 2）工具评估研究的方法学质量。我们通过拟合分层汇总ROC（HSROC）非线性混合模型估计汇总接受者操作特征（SROC）曲线。我们使用HSROC模型参数探索异质性来源。我们在SAS统计软件包和R软件中进行所有分析。
我们纳入了23项研究（n = 4192），评估IL - 6对成年重症患者脓毒症诊断的准确性。仅作为会议论文提供的20项研究正在等待分类。纳入的参与者在年龄、性别、主要诊断、环境、国家、阳性阈值、脓毒症标准、发表年份和感染源等因素的分布上存在异质性。脓毒症的患病率在各研究中差异很大，范围从12%到78%。由于与QUADAS - 2中的索引测试领域相关的问题，我们认为所有研究都存在高度偏倚风险。SROC曲线显示个体研究准确性估计值存在很大离散度（21项研究，3650名成年患者），因此收集数据中的相当大异质性使我们无法计算正式的准确性估计值。使用脓毒症固定患病率50%和固定特异性74%，我们发现敏感性为66%（95%置信区间60至72）。如果我们用IL - 6对1000名疑似脓毒症的成年患者队列进行检测，我们会发现330名患者将接受适当及时的抗生素治疗，而130名患者会被错误地认为患有脓毒症。此外，1000名患者中有370名将避免不必要的抗生素治疗，170名患者脓毒症将未被诊断出来。由于上述局限性，这种数值方法应谨慎解释。
我们对成年重症患者脓毒症诊断中血浆白细胞介素 - 6浓度的证据评估揭示了几个局限性。关于主要诊断、环境、国家、阳性阈值、脓毒症标准、发表年份和感染源等因素，收集的证据存在高度异质性，以及潜在的错误分类数量，仍然是其实施的重大限制。被评估为等待分类研究的20篇会议论文一旦完全发表并评估，可能会改变综述的结论。需要进一步开展关于白细胞介素 - 6对成年脓毒症诊断准确性的研究，这些研究应采用严格的方法进行诊断测试准确性研究。一旦等待发表的20项研究完全发表并纳入，综述的结论可能会改变。
