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

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.

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Optimizing Cerebral Autoregulation May Decrease Neonatal Regional Hypoxic-Ischemic Brain Injury

Developmental Neuroscience ◽

10.1159/000452833 ◽

2016 ◽

Vol 39 (1-4) ◽

pp. 248-256 ◽

Cited By ~ 30

Author(s):

Jennifer K. Lee ◽

Andrea Poretti ◽

Jamie Perin ◽

Thierry A.G.M. Huisman ◽

Charlamaine Parkinson ◽

...

Keyword(s):

Blood Pressure ◽

Brain Injury ◽

White Matter ◽

Near Infrared ◽

Birth Asphyxia ◽

Neurologic Injury ◽

Ischemic Brain ◽

Arterial Blood ◽

Blood Pressures ◽

The Mean

Background: Therapeutic hypothermia provides incomplete neuroprotection for neonatal hypoxic-ischemic encephalopathy (HIE). We examined whether hemodynamic goals that support autoregulation are associated with decreased brain injury and whether these relationships are affected by birth asphyxia or vary by anatomic region. Methods: Neonates cooled for HIE received near-infrared spectroscopy autoregulation monitoring to identify the mean arterial blood pressure with optimized autoregulatory function (MAPOPT). Blood pressure deviation from MAPOPT was correlated with brain injury on MRI after adjusting for the effects of arterial carbon dioxide, vasopressors, seizures, and birth asphyxia severity. Results: Blood pressure deviation from MAPOPT related to neurologic injury in several regions independent of birth asphyxia severity. Greater duration and deviation of blood pressure below MAPOPT were associated with greater injury in the paracentral gyri and white matter. Blood pressure within MAPOPT related to lesser injury in the white matter, putamen and globus pallidus, and brain stem. Finally, blood pressures that exceeded MAPOPT were associated with reduced injury in the paracentral gyri. Conclusions: Blood pressure deviation from optimal autoregulatory vasoreactivity was associated with MRI markers of brain injury that, in many regions, were independent of the initial birth asphyxia. Targeting hemodynamic ranges to optimize autoregulation has potential as an adjunctive therapy to hypothermia for HIE.

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Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia

Journal of Neurophysiology ◽

10.1152/jn.00353.2015 ◽

2015 ◽

Vol 114 (2) ◽

pp. 818-824 ◽

Cited By ~ 31

Author(s):

An N. Massaro ◽

R. B. Govindan ◽

Gilbert Vezina ◽

Taeun Chang ◽

Nickie N. Andescavage ◽

...

Keyword(s):

Brain Injury ◽

Cerebral Autoregulation ◽

Near Infrared ◽

Right Hemisphere ◽

Adverse Outcomes ◽

Direct Care ◽

Hypoxic Ischemic Encephalopathy ◽

Perinatal Brain Injury ◽

Arterial Blood ◽

Ischemic Encephalopathy

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury.

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Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy

American Journal of Perinatology ◽

10.1055/s-0040-1715822 ◽

2020 ◽

Author(s):

Abigail Flower ◽

Daniel Vasiliu ◽

Tianrui Zhu ◽

Robert Andris ◽

Maryam Abubakar ◽

...

Keyword(s):

Blood Pressure ◽

Frequency Domain ◽

Arterial Blood Pressure ◽

Apgar Score ◽

Blood Pressure Variability ◽

Hypoxic Ischemic Encephalopathy ◽

Arterial Blood ◽

The Mean ◽

Minute Apgar Score ◽

Ischemic Encephalopathy

Objective This study aimed to evaluate the role of an objective physiologic biomarker, arterial blood pressure variability, for the early identification of adverse short-term electroencephalogram (EEG) outcomes in infants with hypoxic-ischemic encephalopathy (HIE). Study Design In this multicenter observational study, we analyzed blood pressure of infants meeting these criteria: (1) neonatal encephalopathy determined by modified Sarnat exam, (2) continuous mean arterial blood pressure (MABP) data between 18 and 27 hours after birth, and (3) continuous EEG performed for at least 48 hours. Adverse outcome was defined as moderate–severe grade EEG at 48 hours. Standardized signal preprocessing was used; the power spectral density was computed without interpolation. Multivariate binary logistic regression was used to identify which MABP time and frequency domain metrics provided improved predictive power for adverse outcomes compared with standard clinical predictors (5-minute Apgar score and cord pH) using receiver operator characteristic analysis. Results Ninety-one infants met inclusion criteria. The mean gestational age was 38.4 ± 1.8 weeks, the mean birth weight was 3,260 ± 591 g, 52/91 (57%) of infants were males, the mean cord pH was 6.95 ± 0.21, and 10/91 (11%) of infants died. At 48 hours, 58% of infants had normal or mildly abnormal EEG background and 42% had moderate or severe EEG backgrounds. Clinical predictor variables (10-minute Apgar score, Sarnat stage, and cord pH) were modestly predictive of 48 hours EEG outcome with area under curve (AUC) of 0.66 to 0.68. A composite model of clinical and optimal time- and frequency-domain blood pressure variability had a substantially improved AUC of 0.86. Conclusion Time- and frequency-domain blood pressure variability biomarkers offer a substantial improvement in prediction of later adverse EEG outcomes over perinatal clinical variables in a two-center cohort of infants with HIE. Key Points

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The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15607881 ◽

2015 ◽

Vol 36 (6) ◽

pp. 1075-1086 ◽

Cited By ~ 23

Author(s):

Jessica L Wisnowski ◽

Tai-Wei Wu ◽

Aaron J Reitman ◽

Claire McLean ◽

Philippe Friedlich ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Energy Demand ◽

Cerebral Metabolism ◽

Brain Regions ◽

Hypoxic Ischemic Encephalopathy ◽

Cerebral White Matter ◽

Similar Degree ◽

Resonance Spectroscopy ◽

Ischemic Encephalopathy

Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy (1H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

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Is Erythropoietin Combining with Therapeutic Hypothermia an Efficient and Safe Therapy in Neonatal Hypoxic Ischemic Encephalopathy: A Prospective and Randomized Clinical Trial

10.21203/rs.3.rs-26962/v1 ◽

2020 ◽

Author(s):

Liang-yan Zou ◽

Bing-xue Huang ◽

Peng Zhang ◽

Guo-qiang Cheng ◽

Chun-mei Lu ◽

...

Keyword(s):

Brain Injury ◽

Adverse Events ◽

Therapeutic Hypothermia ◽

Brain Mri ◽

Adverse Outcomes ◽

Hypoxic Ischemic Encephalopathy ◽

Control Group ◽

Term Infants ◽

Basal Nuclei ◽

Ischemic Encephalopathy

Abstract BackgroundTo evaluate the efficacy and safety of erythropoietin (Epo) combined with therapeutic hypothermia (TH) in neonatal hypoxic-ischemic encephalopathy (HIE).MethodsA total of 78 term infants with HIE were assigned randomly to receive Epo (n = 40) or placebo (n = 38). All infants received TH. Blood samples before TH, after TH and after Epo/placebo were collected for measuring TH associated adverse events, Epo associated factors and potential neural biomarkers. Basal ganglia/ watershed (BG/W) scoring system was used to assess brain injury in MRI. Neurodevelopmental evaluations were performed at 18 months by using BayleyScales of Infant Development II (Bayley II).ResultsEpo-treated group tend to have lower serum creatine kinase (CK) concentration (114 vs 202, P = .04) and higher serum K+, Mg2+ concentration (5.0 vs 4.5, P = .03; 1.0 vs 0.9, P = .02) than control group after intervention. Brain MRI was performed in 65 (83%) neonatal. Totally brain injury score was in even distribution between two groups (median, 0 vs 0, P = .61), but injury region in cortex plus basal nuclei comparing with in basal nuclei solely was less common in the Epo than in the control group (21% vs 31%, P = .046). Only forty patients (40/78, 51%) succeeded in achieving 18-month follow up data. The totally adverse outcomes were trend to decline in the Epo group (35% vs 60%, P = .21). No adverse events were ascribed to Epo treatment.ConclusionsThe combination of Epo and TH is proved to be feasible, safe and potential effective.Trial registration: ChiCTR-TRC-14004532, date of registration: April 18th, 2014.

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Predictors of Long-Term Neurodevelopmental Outcome of Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Seminars in Neurology ◽

10.1055/s-0040-1702939 ◽

2020 ◽

Vol 40 (03) ◽

pp. 322-334

Author(s):

Ipsita Goswami ◽

Mireille Guillot ◽

Emily W. Y. Tam

Keyword(s):

Brain Injury ◽

Therapeutic Hypothermia ◽

Prognostic Markers ◽

Neurodevelopmental Outcome ◽

Hypoxic Ischemic Encephalopathy ◽

Secondary Brain Injury ◽

Prognostic Utility ◽

Initial Injury ◽

Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE) is a manifestation of perinatal asphyxial insult that continues to evolve over days to weeks following the initial injury. Therapeutic hypothermia has demonstrated that a proportion of this secondary brain injury may indeed be preventable. However, therapeutic hypothermia has also altered the prognostic utility of many bedside tools that are commonly used as predictors of long-term neurodevelopmental outcome in HIE. Clinicians are often confronted with uncertainty when assessing the prognosis of infants with HIE. Improved understanding of the implications and limitations of individual investigations may inform clinical decisions and allow for timely intervention. This review summarizes the predictive value of currently available prognostic markers in HIE infants in the therapeutic hypothermia era, including clinical, biochemical, neurophysiological, physiological, and neuroimaging predictors.

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Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy

Pediatric Research ◽

10.1038/pr.2015.280 ◽

2015 ◽

Vol 79 (5) ◽

pp. 742-747 ◽

Cited By ~ 29

Author(s):

Janet E. Orrock ◽

Karuna Panchapakesan ◽

Gilbert Vezina ◽

Taeun Chang ◽

Kari Harris ◽

...

Keyword(s):

Brain Injury ◽

Therapeutic Hypothermia ◽

Cytokine Response ◽

Hypoxic Ischemic Encephalopathy ◽

Ischemic Encephalopathy

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Impaired cerebral autoregulation and elevation in plasma glial fibrillary acidic protein level during cardiopulmonary bypass surgery for CHD

Cardiology in the Young ◽

10.1017/s1047951117001573 ◽

2017 ◽

Vol 28 (1) ◽

pp. 55-65 ◽

Cited By ~ 8

Author(s):

Ronald B. Easley ◽

Bradley S. Marino ◽

Jacky Jennings ◽

Amy E. Cassedy ◽

Kathleen K. Kibler ◽

...

Keyword(s):

Blood Pressure ◽

Cardiopulmonary Bypass ◽

Brain Injury ◽

Glial Fibrillary Acidic Protein ◽

Lower Limit ◽

Cerebrovascular Reactivity ◽

Acidic Protein ◽

Volume Index ◽

Arterial Blood ◽

The Mean

AbstractBackgroundCerebrovascular reactivity monitoring has been used to identify the lower limit of pressure autoregulation in adult patients with brain injury. We hypothesise that impaired cerebrovascular reactivity and time spent below the lower limit of autoregulation during cardiopulmonary bypass will result in hypoperfusion injuries to the brain detectable by elevation in serum glial fibrillary acidic protein level.MethodsWe designed a multicentre observational pilot study combining concurrent cerebrovascular reactivity and biomarker monitoring during cardiopulmonary bypass. All children undergoing bypass for CHD were eligible. Autoregulation was monitored with the haemoglobin volume index, a moving correlation coefficient between the mean arterial blood pressure and the near-infrared spectroscopy-based trend of cerebral blood volume. Both haemoglobin volume index and glial fibrillary acidic protein data were analysed by phases of bypass. Each patient’s autoregulation curve was analysed to identify the lower limit of autoregulation and optimal arterial blood pressure.ResultsA total of 57 children had autoregulation and biomarker data for all phases of bypass. The mean baseline haemoglobin volume index was 0.084. Haemoglobin volume index increased with lowering of pressure with 82% demonstrating a lower limit of autoregulation (41±9 mmHg), whereas 100% demonstrated optimal blood pressure (48±11 mmHg). There was a significant association between an individual’s peak autoregulation and biomarker values (p=0.01).ConclusionsIndividual, dynamic non-invasive cerebrovascular reactivity monitoring demonstrated transient periods of impairment related to possible silent brain injury. The association between an impaired autoregulation burden and elevation in the serum brain biomarker may identify brain perfusion risk that could result in injury.

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