Heart Rate Characteristics: Physiomarkers for Detection of Late-Onset Neonatal Sepsis

Early detection of late-onset neonatal sepsis, before the onset of obvious and potentially catastrophic clinical signs, is an important goal in neonatal medicine. Sepsis causes a well-known series of physiologic changes including abnormalities of blood pressure, respiration, temperature, and heart rate, and less well-known changes in heart rate variability. Although vital signs are frequently or continuously monitored in patients in the neonatal intensive care unit (NICU), changes in these parameters are subtle in the early phase of sepsis and difficult to interpret using traditional NICU monitoring tools. A new tool, continuous monitoring of heart rate characteristics (HRC), is now available for clinical use. Recent research has established that 2 abnormalities of HRC that have long been used by obstetricians to identify fetal compromise, reduced heart rate variability and transient decelerations, occur early in the course of sepsis in patients in the NICU, often before clinical signs of illness. Through mathematical modeling of electrocardiogram data from hundreds of patients in the NICU, an HRC index that represents the fold increase in risk that a neonate will be diagnosed with clinical or culture-proven sepsis within the next 24 hours was derived. The effect of continuous HAG monitoring on outcomes in preterm very low birth weight infants is the subject of a multicenter randomized clinical trial of 3000 patients, which will be complete in 2010. Further research into mechanisms of abnormal HAG and regulation of autonomic nervous system function in sepsis and other disease processes will shed light on additional applications of this exciting new technology.