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A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats
Published on: February 20, 2021
The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections
Lonneke A van Vught1,2, Maryse A Wiewel1,2, Arie J Hoogendijk1,2
11 Center for Experimental and Molecular Medicine.
Rationale:
Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses.
Objectives:
To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not.
Methods:
Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication.
Measurements And Main Results:
Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications.
Conclusions:
Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.
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