Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study

PLoS One. 2022 Oct 27;17(10):e0267517. doi: 10.1371/journal.pone.0267517. eCollection 2022.

Abstract

Background: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates.

Methods: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters.

Results: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers.

Conclusions: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies.

Trial registration: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

Publication types

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

MeSH terms

  • Biomarkers
  • Cluster Analysis
  • Cohort Studies
  • Humans
  • Intensive Care Units
  • Middle Aged
  • Prospective Studies
  • Sepsis* / diagnosis
  • Sepsis* / therapy

Substances

  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT01378169

Grants and funding

Grant from the Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC AOM 09143) and from the Institut Mérieux-Institut Pasteur collaborative research partnership. The study was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique-Hôpitaux de Paris. This project was part of Advanced Diagnostics for New Therapeutic Approaches, a program dedicated to personalized medicine, coordinated by Mérieux Alliance and supported by the French public agency, OSEO. These funding sources had no role in the design of this study, analyses, interpretation of the data, or decision to submit the results.