Abstract
Dysfunctional cerebrovascular autoregulation may contribute to neurologic injury in neonatal hypoxic-ischemic encephalopathy (HIE). Identifying the optimal mean arterial blood pressure (MAPopt) that best supports autoregulation could help identify hemodynamic goals that support neurologic recovery. In neonates who received therapeutic hypothermia for HIE, we hypothesized that the wavelet hemoglobin volume index (wHVx) would identify MAPopt and that blood pressures closer to MAPopt would be associated with less brain injury on MRI. We also tested a correlation-derived hemoglobin volume index (HVx) and single- and multi-window data processing methodology. Autoregulation was monitored in consecutive 3-h periods using near infrared spectroscopy in an observational study. The neonates had a mean MAP of 54 mmHg (standard deviation: 9) during hypothermia. Greater blood pressure above the MAPopt from single-window wHVx was associated with less injury in the paracentral gyri (p = 0.044; n = 63), basal ganglia (p = 0.015), thalamus (p = 0.013), and brainstem (p = 0.041) after adjustments for sex, vasopressor use, seizures, arterial carbon dioxide level, and a perinatal insult score. Blood pressure exceeding MAPopt from the multi-window, correlation HVx was associated with less injury in the brainstem (p = 0.021) but not in other brain regions. We conclude that applying wavelet methodology to short autoregulation monitoring periods may improve the identification of MAPopt values that are associated with brain injury. Having blood pressure above MAPopt with an upper MAP of ~50–60 mmHg may reduce the risk of brain injury during therapeutic hypothermia. Though a cause-and-effect relationship cannot be inferred, the data support the need for randomized studies of autoregulation and brain injury in neonates with HIE.
Highlights
MATERIALS AND METHODSNearly one million neonatal deaths worldwide each year are related to hypoxic-ischemic encephalopathy (HIE) from intrapartum complications [1]
Autoregulation was monitored for a mean total of 54.4 h [standard deviation (SD): 21.7 h; 95% confidence interval (CI): 49.5, 59.1 h] in all neonates
We tested whether wavelet hemoglobin volume index (wHVx) and correlation hemoglobin volume index (HVx), which we validated in piglets with HIE [13], and single- and multi-window methodology [14] identify MAPopt in short monitoring periods
Summary
One million neonatal deaths worldwide each year are related to hypoxic-ischemic encephalopathy (HIE) from intrapartum complications [1]. Blood pressures below the optimal MAP (MAPopt) at which autoregulation is most robust are associated with greater brain injury on MRI and worse neurocognitive outcomes in neonates with HIE [4,5,6,7]. MAPopt values calculated by the single- and multi-window methods from HVx and wHVx in each 3-h period across hypothermia, rewarming, and the transition between rewarming and normothermia. The associations between each neonate’s autoregulation and brain injury parameters were analyzed with adjustments for sex, PaCO2 level, perinatal insult score, vasopressor use, and presence of electroencephalographic seizures. When analyzing the maximal blood pressure above MAPopt during hypothermia, 24 tests compared MAPopt from single- and multi-window wHVx and correlation HVx (four types of MAPopt) in 6 brain regions. The regional injury score, which required interpretation of T1, T2, and diffusion tensor imaging (DTI) MRI, was completed in only 68 neonates because two had motion artifact on DTI
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