Sepsis is a life-threatening condition caused by a severe body response to an infection. Sepsis is a common cause of multiple organ dysfunction syndrome in children, which is when two or more organs start failing, like the heart, kidneys, lungs, etc. This, in turn, is a final common pathway for death in many of these critically ill children. Sepsis and multiple organ dysfunction syndrome are complex, dynamic (i.e. subject to change), and heterogenous (i.e. not all patients present the same way). In other words, two patients may both be diagnosed with sepsis, but they may have very different clinical characteristics and risk factors and potentially require very different treatments during their illness. We would say that these two patients have different “phenotypes”. By extension, two patients who have very similar characteristics, risk factors, and response to treatments are likely having the same phenotype of sepsis.
Many researchers have been focusing their efforts in better defining these phenotypes, or distinct subgroups of patients with sepsis, by looking at the structural, functional, and chemical abnormalities occurring at a cellular level. Our project, however, is taking a different approach. We believe that the dynamic pattern of organ dysfunction of patients with sepsis can be used as surrogates of the underlying pathology an can help us group patients into distinct phenotypes. We also believe these phenotypes will help us better predict the likely outcome of these patients and determine the type of medications that may be particularly useful or harmful to them.
Our project brings together leaders in pediatric critical care medicine from across the United States, and aligns with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) mission to advance our understanding of multiple organ dysfunction syndrome in children. The goals of the study are to: (1) re-calibrate and validate an existing measure of organ dysfunction based on data collected in the electronic health record (EHR) of patients; (2) analyze the early patterns of organ dysfunction in critically ill children with sepsis to uncover novel phenotypes; and (3) determine whether these phenotypes are associated with different outcomes and response to therapy. To perform this study we will be extracting and analyzing data from the EHRs of over 30,000 patients with infections in nine pediatric intensive care units in the United States. This research is being supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number R21HD096402.