Autonomic Dysfunction in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia Impairs Physiological Responses to Routine Care Events

Abstract

To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia. Videos between 16 and 24 hours of age identified 99 distinct care events, including stimulating events (diaper changes, painful procedures), and vagal stimuli (endotracheal tube manipulations, pupil examinations). Pre-event HR variability was used to stratify patients into groups with impaired versus intact autonomic nervous system (ANS) function. Postevent physiological responses were compared between groups with the nearest mean classification approach. Infants with intact ANS had increases in HR/BP after stimulating events, whereas those with impaired ANS showed no change or decreased HR/BP. With vagal stimuli, the HR decreased in infants with intact ANS but changed minimally in those with impaired ANS. A pupil examination in infants with an intact ANS led to a stable or increased BP, whereas the BP decreased in the group with an impaired ANS. Near infrared spectroscopy measures of cerebral blood flow/blood volume increased after diaper changes in infants with an impaired ANS, but were stable or decreased in those with an intact ANS. HR variability metrics identified infants with impaired ANS function at risk for maladaptive responses to care events. These data support the potential use of HR variability as a real-time, continuous physiological biomarker to guide neuroprotective care in high-risk newborns.