Wavelet Autoregulation Monitoring Identifies Blood Pressures Associated With Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy

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.

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia

“…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 ). These studies showed that the extent of autoregulatory disturbances during hypothermia and rewarming are associated with injury severity and adverse neurodevelopmental outcomes.…”

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

“…Continuous NIRS blood pressure autoregulation monitoring after neonatal HIE can identify neonates at greatest risk of brain injury or death. Despite years of neonatal au-toregulation research [6,8,10,14,30,[33][34][35], an optimal autoregulation index has not been integrated into clinical practice. We undertook the current study to examine three candidate autoregulation indices that have shown promise in preclinical [15] and single-center clinical [7][8][9][10][11]36] HIE studies.…”

“…Since all our autoregulation indices become positive when blood pressure is below or above the limits of autoregulation, we cannot conclude whether the link between dysfunctional autoregulation and poor outcome were weighted towards hypo- or hypertension. However, prior research indicates that blood pressure below the optimal autoregulatory range is the larger contributor to brain injury [8-11, 14, 36]. While prior approaches have focused on identifying the optimal MAP with most robust autoregulation, optimal MAP cannot be identified in all neonates [11].…”

“…Cerebral autoregulation holds CBF relatively steady across changes in mean arterial blood pressure (MAP) through vasoreactivity. Autoregulatory function during therapeutic hypothermia has been shown to be associated with neurologic outcomes in multiple studies of HIE [6][7][8][9][10][11][12][13][14]. Despite evidence that autoregulation monitoring could help clarify hemodynamic goals that optimize cerebral vasoreactivity, no autoregulation metric has been proposed in neonatal clinical care medicine.…”

Analgesia and sedation strategies in neonates undergoing whole-body therapeutic hypothermia: A scoping review

“…Table 3 summarizes all multicentre studies and surveys that describe the types of sedation/analgesia practices [34,[48][49][50][51][52][53]. Seven studies mentioned using "routine" sedation for all neonates undergoing TH [29,37,[54][55][56][57][58]. Gagne-Loranger et al reported the results from a prospective study (2008-2012) in which neonates were not regularly sedated during TH but received boluses of morphine only if they were uncomfortable [59].…”