The Utility of Cerebral Autoregulation Indices in Detecting Severe Brain Injury Varies by Cooling Treatment Phase in Neonates with Hypoxic-Ischemic Encephalopathy

Abstract

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiological marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency of maximum coherence. The HVx is the correlation coefficient between MAP and THb. The PPI is the percentage of coherent MAP-DHb (difference between oxygenated and deoxygenated hemoglobin, a marker of cerebral blood flow) epochs in a chosen time period. Neonates cooled for HIE were prospectively enrolled in an observational study in two neonatal intensive care units. In analyses adjusted for study site and encephalopathy level, all indices detected relationships between poor autoregulation in the first 6 h after rewarming with a higher injury score on MRI. Only HVx and PPI during hypothermia and the PPI during rewarming identified autoregulatory dysfunction associated with a poor outcome independent of study site and encephalopathy level. Our findings suggest that the accuracy of mathematical autoregulation algorithms in detecting the risk of brain injury or death may depend on temperature and postnatal age. Extending autoregulation monitoring beyond the standard 72 hours of therapeutic hypothermia may serve as a method to provide personalized care by assessing the need for and efficacy of future therapies extending past the hypothermia treatment phase.

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia

“…These studies showed that the extent of autoregulatory disturbances during hypothermia and rewarming are associated with injury severity and adverse neurodevelopmental outcomes. It is important to note that measures during normothermia after rewarming were more predictive of adverse outcomes, highlighting again the impact of hypothermia on brain activity, and the potential value of neuromonitoring after rewarming ( 56 ).…”

“…Cerebral autoregulation is a physiological mechanism that maintains relatively stable cerebral blood flow during changes in blood pressure. Multiple studies in term infants with moderate-severe HIE have reported impaired cerebral autoregulation during and after therapeutic hypothermia ( 55 , 56 ). Recent studies have refined time and frequency domain analysis of NIRS parameters to quantify autoregulatory disturbances, such as spectral coherence analysis of mean arterial pressure (MAP) and NIRS parameters (hemoglobin difference) to calculate pressure passivity, moving correlation coefficient between MAP and relative total tissue hemoglobin concentration to calculate time spent below optimal MAP (range of MAP with the most dynamic vascular reactivity), and wavelet-coherence analysis of MAP and cerebral oxygen saturation ( 55 , 57 , 58 ).…”

Ultrasound Diagnosis and Near-Infrared Spectroscopy in the Study of Encephalopathy in Neonates Born under Asphyxia: Narrative Review

“…After asphyxia, therapeutic intervention may include adjustment of hemodynamic parameters to improve autoregulatory function. Depending on the clinical situation, either vasoactive drugs or intravascular volume support can be used [29]. Blood pressure deviations below MAPOPT (mean arterial pressure optimized for autoregulation) were associated with greater white matter and paracentral gyri damage in children with HIE.…”