Data-driven discovery of a novel sepsis pre-shock state predicts impending septic shock in the ICU

Septic shock is a life-threatening condition in which timely treatment substantially reduces mortality. Reliable identification of patients with sepsis who are at elevated risk of developing septic shock therefore has the potential to save lives by opening an early window of intervention. We hypothesize the existence of a novel clinical state of sepsis referred to as the "pre-shock" state, and that patients with sepsis who enter this state are highly likely to develop septic shock at some future time. We apply three different machine learning techniques to the electronic health record data of 15,930 patients in the MIMIC-III database to test this hypothesis. This novel paradigm yields improved performance in identifying patients with sepsis who will progress to septic shock, as defined by Sepsis- 3 criteria, with the best method achieving a 0.93 area under the receiver operating curve, 88% sensitivity, 84% specificity, and median early warning time of 7 hours. Additionally, we introduce the notion of patient-specific positive predictive value, assigning confidence to individual predictions, and achieving values as high as 91%. This study demonstrates that early prediction of impending septic shock, and thus early intervention, is possible many hours in advance.