Methods for Phenotyping Adult Patients in Sepsis and Septic Shock: A Scoping Review

Abstract

Despite its heterogeneous phenotypes, sepsis or life-threatening dysfunction in response to infection is often treated empirically. Identifying patient subgroups with unique pathophysiology and treatment response is critical to the advancement of sepsis care. However, phenotyping methods and results are as heterogeneous as the disease itself. This scoping review evaluates the prognostic capabilities and treatment implications of adult sepsis and septic shock phenotyping methods.

Data sources: Medline and Embase.

Study selection: We included clinical studies that described sepsis or septic shock and used any clustering method to identify sepsis phenotypes. We excluded conference abstracts, literature reviews, comments, letters to the editor, and in vitro studies. We assessed study quality using a validated risk of bias tool for observational cohort and cross-sectional studies.

Data extraction: We extracted population, methodology, validation, and phenotyping characteristics from 17 studies.

Data synthesis: Sepsis phenotyping methods most frequently grouped patients based on the degree of inflammatory response and coagulopathy using clinical, nongenomic variables. Five articles clustered patients based on genomic or transcriptomic data. Seven articles generated patient subgroups with differential response to sepsis treatments. Cluster clinical characteristics and their associations with mortality and treatment response were heterogeneous across studies, and validity was evaluated in nine of 17 articles, hindering pooled analysis of results and derivation of universal truths regarding sepsis phenotypes, their prognostic capabilities, and their associations with treatment response.

Conclusions: Sepsis phenotyping methods can identify high-risk patients and those with high probability of responding well to targeted treatments. Research quality was fair, but achieving generalizability and clinical impact of sepsis phenotyping will require external validation and direct comparison with alternative approaches.

Keywords: cluster analyses; infections; machine learning; risk assessment; sepsis; septic shock.

Figure 1.

Preferred Reporting Items for Systematic Review diagram of study selection.

Figure 2.

Study risk of bias assessments and reasoning. APACHE = Acute Physiology And Chronic Health Evaluation, EMR = Electronic Medical Record, SOFA = Sequential Organ Failure Assessment.