Abstract:Sepsis is a life-threatening condition triggered by an extreme infection response. Our objective is to forecast sepsis patient outcomes using their medical history and treatments, while learning interpretable state representations to assess patients' risks in developing various adverse outcomes. While neural networks excel in outcome prediction, their limited interpretability remains a key issue. In this work, we use knowledge distillation via constrained variational inference to distill the knowledge of a powerful "teacher" neural network model with high predictive power to train a "student" latent variable model to learn interpretable hidden state representations to achieve high predictive performance for sepsis outcome prediction. Using real-world data from the MIMIC-IV database, we trained an LSTM as the "teacher" model to predict mortality for sepsis patients, given information about their recent history of vital signs, lab values and treatments. For our student model, we use an autoregressive hidden Markov model (AR-HMM) to learn interpretable hidden states from patients' clinical time series, and use the posterior distribution of the learned state representations to predict various downstream outcomes, including hospital mortality, pulmonary edema, need for diuretics, dialysis, and mechanical ventilation. Our results show that our approach successfully incorporates the constraint to achieve high predictive power similar to the teacher model, while maintaining the generative performance.