Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study
Issued Date
2022-01-01
Resource Type
ISSN
03424642
eISSN
14321238
Scopus ID
2-s2.0-85121140584
Journal Title
Intensive Care Medicine
Volume
48
Issue
1
Start Page
92
End Page
102
Rights Holder(s)
SCOPUS
Bibliographic Citation
Intensive Care Medicine Vol.48 No.1 (2022) , 92-102
Suggested Citation
Peters-Sengers H. Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study. Intensive Care Medicine Vol.48 No.1 (2022) , 92-102. 102. doi:10.1007/s00134-021-06574-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86720
Title
Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study
Author(s)
Other Contributor(s)
Abstract
Purpose: There is limited knowledge on how the source of infection impacts the host response to sepsis. We aimed to compare the host response in sepsis patients with a single, known source at admission (< 24 h) to the intensive care unit. Methods: From the molecular diagnosis and risk stratification of sepsis (MARS) prospective cohort, we measured 16 plasma host response biomarkers reflective of key host response pathways in 621 sepsis patients. In a subgroup (n = 335), blood leukocyte transcriptomes were compared between the sources. Differences in clinical patient profiles and survival were compared in the whole sepsis cohort (n = 2019). Results: The plasma biomarker cohort was categorized into sepsis originating from the respiratory tract (n = 334, 53.8%), abdomen (n = 159, 25.6%), urinary tract (n = 44, 7.1%), cardiovascular (n = 41, 6.6%), central nervous system (CNS) (n = 18, 2.9%), or skin (n = 25, 4%). This analysis revealed stronger inflammatory and cytokine responses, loss of vascular integrity and coagulation activation in abdominal sepsis relative to respiratory. Endothelial cell activation was prominent in urinary, cardiovascular and skin infections, while CNS infection was associated with the least host response aberrations. The leukocyte transcriptional response showed the largest overlap between abdominal and pulmonary infections (76% in common); notable differences between the sources were detected regarding hemostasis, cytokine signaling, innate and adaptive immune, and metabolic transcriptional pathways. After adjustment for confounders, the source of infection remained an independent contributor to 30-day mortality (unadjusted p = 0.001, adjusted p = 0.028). Conclusion: Sepsis heterogeneity is partly explained by source-specific host response dysregulations and should be considered when selecting patients for trials testing immune modulatory drugs.