Network-Based Modeling of Sepsis: Quantification and Evaluation of Simultaneity of Organ Dysfunctions

It is shown that appropriate therapeutic management at early stages of sepsis are crucial for preventing further deterioration and irreversible organ damage. Although previous studies considered the cellular and physiological responses as the components of sepsis-related predictive models, temporal connections among the responses have not been widely studied. The objective of this study is to investigate simultaneous changes in cellular and physiological responses represented by 16 clinical variables contributing to seven organ system dysfunctions in patients with sepsis to predict in-hospital mortality. Organ dysfunctions were represented by undirected weighted network models composed of: i) nodes (i.e., 16 clinical variables and three biomarkers including procalcitonin, C-reactive protein, and sedimentation rate), ii) edges (i.e., connection between pair of nodes representing simultaneous dysfunctions), and iii) weights representing the persistence of the co-occurrence of two dysfunctions. Data was collected from 13,367 adult patients (corresponding to 17,953 visits) admitted to the study hospital from July 1, 2013, to December 31, 2015. The study population were categorized based on clinical criteria representing sepsis progression to identify different subpopulations. The findings quantify the optimal window for defining the simultaneity of two dysfunctions, the network properties corresponding to different subpopulations, the discriminatory patterns of simultaneous dysfunctions among subpopulations and in-hospital mortality prediction. The results show that the level of persistence of simultaneous dysfunctions are subpopulation-specific. Insights from this study regarding optimal thresholds of the persistence and combination of simultaneous organ dysfunctions can inform policies to personalize the in-hospital mortality prediction.