Six subphenotypes in septic shock: Latent class analysis of the PROWESS Shock study

Abstract

Purpose: Septic shock is a highly heterogeneous condition which is part of the challenge in its diagnosis and treatment. In this study we aim to identify clinically relevant subphenotypes of septic shock using a novel statistic al approach.

Methods: Baseline patient data from a large global clinical trial of septic shock (n = 1696) was analysed using latent class analysis (LCA). This approach allowed investigators to identify subgroups in a heterogeneous population by estimating a categorical latent variable that detects relatively homogeneous subgroups within a complex phenomenon.

Results: LCA identified six different, clinically meaningful subphenotypes of septic shock each with a typical profile: (1) "Uncomplicated Septic Shock, (2) "Pneumonia with adult respiratory distress syndrome (ARDS)", (3) "Postoperative Abdominal", (4) "Severe Septic Shock", (5): "Pneumonia with ARDS and multiple organ dysfunction syndrome (MODS)", (6) "Late Septic Shock". The 6-class solution showed high entropy approaching 1 (i.e., 0.92), indicating there was excellent separation between estimated classes.

Conclusions: LCA appears to be an applicable statistical tool in analysing a heterogenous clinical cohort of septic shock. The results may lead to a better understanding of septic shock complexity and form a basis for considering targeted therapies and selecting patients for future clinical trials.

Keywords: Critical illness; Intensive care; Latent class analysis; Sepsis; Septic shock; Subphenotypes.

Conflict of interest statement

Declaration of interest

No author declared competing interests. Eli Lilly & Co sponsored the original clinical trial but had no role in the present study design, analysis, interpretation or reporting of results. Eli Lilly & Co has, through a previous agreement with the Academic Steering Committee for the original trial, released the entire clinical database to an independent academic centre (Duke University Medical Center) for use in further scientific studies. The corresponding author had full access to all data and final responsibility for the decision to submit the manuscript for publication.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Fig. 1.

a Graphical representation of frequencies (%) of categorical variables in the 6 subphenotypes. b Graphical representation (standardized z-score) of continuous variables in the 6 subphenotypes.

Fig. 2.

Kaplan-Meier 90 day survival plot for the 6 subphenotypes.

Fig. 3.

Location of patients (dead, ICU, hospital ward or discharged from hospital) during 28 days for the six subphenotypes.

Fig. 4.

Fraction of patients on CRRT (continuous renal replacement therapy) over 28 days for the six subphenotypes.