Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults
Por:
Molano Franco D., Arevalo-Rodriguez I., Roqué i Figuls M., Montero Oleas N.G., Nuvials X., Zamora J.
Publicada:
1 ene 2019
Resumen:
Background: 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. Objectives: To determine the diagnostic accuracy of plasma interleukin-6 (IL-6) concentration for the diagnosis of bacterial sepsis in critically ill adults. Search methods: 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. Selection criteria: 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. Data collection and analysis: 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. Main results: 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. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Filiaciones:
Molano Franco D.:
Fundacion Universitaria de Ciencias de la Salud, Hospital de San José, Department of Critical Care, Carrera 19 # 8-32, Bogota, Bogota 11001, Colombia
Arevalo-Rodriguez I.:
Hospital Universitario Ramón y Cajal (IRYCIS). CIBER Epidemiology and Public Health (CIBERESP), Clinical Biostatistics Unit, Ctra. Colmenar Km. 9,100, Madrid, 28034, Spain
Cochrane Associate Centre of Madrid, Madrid, Spain
Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Centro Asociado Cochrane de Ecuador, Quito, Ecuador
Roqué i Figuls M.:
CIBER Epidemiología y Salud Pública (CIBERESP), Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Sant Antoni Maria Claret 171, Edifici Casa de Convalescència, Barcelona, Catalunya 08041, Spain
Montero Oleas N.G.:
Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Centro Asociado Cochrane de Ecuador, Quito, Ecuador
Nuvials X.:
Hospital Vall d’Hebron, Department of Critical Care Medicine, Passeig Vall d’Hebron 119-129, Barcelona, 08035, Spain
Vall d'Hebron Institut de Recerca (VHIR), SODIR research group, Barcelona, Spain
Zamora J.:
Cochrane Associate Centre of Madrid, Madrid, Spain
Women’s Health Research Unit, Centre for Primary Care and Public Health, Queen Mary University of London, London, United Kingdom
Hospital Universitario Ramon y Cajal (IRYCIS). CIBER Epidemiology and Public Health (CIBERESP), Clinical Biostatistics Unit, Madrid, Spain
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