The "neurovascular unit approach" to evaluate mechanisms of dysfunctional autoregulation in asphyxiated newborns in the era of hypothermia therapy

Abstract

Despite improvements in obstetrical and neonatal care, and introduction of hypothermia as a neuroprotective therapy, perinatal brain injury remains a frequent cause of cerebral palsy, mental retardation and epilepsy. The recognition of dysfunction of cerebral autoregulation is essential for a real time measure of efficacy to identify those who are at highest risk for brain injury. This article will focus on the "neurovascular unit" approach to the care of asphyxiated neonates and will address 1) potential mechanisms of dysfunctional cerebral blood flow (CBF) regulation, 2) optimal monitoring methodology such as NIRS (near infrared spectroscopy), and TCD (transcutaneous Doppler), and 3) clinical implications of monitoring in the neonatal intensive care setting in asphyxiated newborns undergoing hypothermia and rewarming. Critical knowledge of the functional regulation of the neurovascular unit may lead to improved ability to predict outcomes in real time during hypothermia, as well as differentiate non-responders who might benefit from additional therapies.

Keywords: HIE; Hypothermia; Neurodevelopmental outcomes; Rewarming.

Copyright © 2014 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Hypothetical diagram illustrating 1a: the response of cerebral and systemic hemodynamics to short asphyxia with adaptive responses ensuring a stable cerebral blood flow and 1b: the response of cerebral and systemic hemodynamics to sustained asphyxia with both reduced cardiac output and cerebral blood flow and the possible effect of hypothermia.

Figure 2

Normal regulation of 2a: cerebral oxygen saturation (rSO2), cerebral fractional tissue oxygen extraction (FTOE), mean arterial pressure (MAP) and 2b: amplitude EEG (aEEG) during 6 hours of hypothermia (left) and re-warming (right). Polynomial line fit was used to show the trend of cerebral and systemic hemodynamic variables over time. Patient maintains normal reference ranges of rSO2 (70-85%) and FTOE (25-35%) as well as continuous aEEG with sleep wake cycles during hypothermia and re-warming. His clinical condition was stable with oxygen saturation of 100% on room air, HR (80 bpm), and MAP (35-45 mmHg). This patient had a normal Bayley III outcome >85 at 24 months.

Figure 3

Impaired regulation of 3a: cerebral oxygen saturation (rSO2), cerebral fractional tissue oxygen extraction (FTOE), mean arterial pressure (MAP) and 3b: amplitude EEG (aEEG) during 6 hours of hypothermia (left) and re-warming (right) . Polynomial line fit was used to show the trend of cerebral and systemic hemodynamic variables over time. Note the persistently increased rSO2 of 95% with a concurrent FTOE of <5%. aEEG revealed a pattern of low voltage discontinuous activity with no sleep wake cycles. Infant had seizures four hours after initiation of re-warming (red arrow). This infant had an abnormal outcome (Bayley III at 24 months: cognitive score 65, motor score 82).