BackgroundSepsis is a potentially life threatening condition that requires prompt recognition and treatment for optimal outcomes. There is little consensus on an objective way to assess for sepsis severity and risk for mortality. In recent years, heart rate variability (HRV), a measure of the cardiac autonomic regulation derived from short electrocardiogram tracings, has been found to correlate with sepsis mortality, and its use as a prognostic variable and for risk stratification has been promising. In this paper, we present using novel heart rate n-variability (HRnV) measures for sepsis mortality risk prediction and compare against current mortality prediction scores. MethodsThis study was a retrospective cohort study on a convenience sample of patients presenting to the emergency department (ED) of Singapore General Hospital between September 2014 to April 2017. Patients were included in the study if they were above 21 years old, were suspected to have sepsis by their attending physician, triaged as emergency or urgent cases, and if they met two or more of the Systemic Inflammatory Response Syndrome (SIRS) criteria. Demographic and clinical variables were obtained from the electronic medical records, and HRV and novel HRnV parameters were calculated from five minute ECG tracings. Univariable analysis was conducted on variables obtained, with the primary outcome being 30-day in-hospital mortality (IHM). Variables selected through univariable analysis and stepwise selection were included in a multivariable logistic regression model, the results of which were presented using receiver operating curve (ROC) analysis. ResultsOf 342 patients included for final analysis, 66 (19%) met with the primary outcome. On univariable analysis, 85 out of 142 analysed HRV and HRnV parameters showed statistical difference between groups. The final multivariable logistic regression model comprised of 21 variables including four vital signs, two HRV parameters, and 15 HRnV parameters. The area under the curve (AUC) of the model was 0.86 (95% confidence interval 0.81-0.90), outperforming several established clinical scores. ConclusionThe use of novel HRnV measures can provide adequate power to predictive models in the risk stratification of patients presenting to the ED with sepsis. When included in a multivariable logistic regression model, the HRnV-based model outperformed traditional risk stratification scoring systems. The HRnV measures may have potential to allow for a rapid, objective, and accurate means of patient risk stratification for sepsis severity and mortality.