Instantaneous frequency analysis shows greater sensitivity to parasympathetic components of heart rate than spectral analysis

Septic shock is a leading cause of hospital deaths in the United States. A system to detect initial immune response to an infection could allow for treatment before septic shock occurs, which would save many lives. Here, we demonstrate the analysis of beat-to-beat heart rate intervals using the Hilbert-Huang transform (HHT) as a method of detection of the immune/inflammatory response. The HHT is ideal for nonlinear nonstationary signals. This works by detecting differences in the heart rate variability (HRV), a marker of autonomic signaling to the heart. The instantaneous frequency (IF) as computed via the HHT was compared with spectral analysis and pNN50, Our data set were beat-to-beat intervals measured from subjects administered bacterial endotoxin ranging in dose from 0.1-2.0 ng/kg. Measurements were compared with placebo. While all measurements accurately differentiated the 2.0 ng/kg dosage and placebo groups, the IF showed improved discrimination at lower dosages. The first mode was found to be most significant for discrimination, though each mode could classify subjects with at least 77% accuracy, indicating that information is contained at many scales within the beat-to-beat intervals. The IF appears to have superior sensitivity to parasympathetic signaling reflected in the beat-to-beat interval.