The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections

Am J Respir Crit Care Med. 2017 Aug 15;196(4):458-470. doi: 10.1164/rccm.201606-1225OC.

Abstract

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.

Keywords: ICU-acquired infection; biomarker; host response; intensive care unit; sepsis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cohort Studies
  • Coinfection / blood*
  • Coinfection / complications
  • Cross Infection / blood*
  • Cross Infection / complications
  • Female
  • Humans
  • Intensive Care Units*
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Prospective Studies
  • Sepsis / blood*
  • Sepsis / complications
  • Severity of Illness Index

Substances

  • Biomarkers