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Continuous neuromonitoring in the neonatal intensive care unit allows for bedside assessment of brain oxygenation and perfusion as well as cerebral function and seizure identification. Near-infrared spectroscopy (NIRS) reflects the balance between oxygen delivery and consumption, and use of multisite monitoring of regional oxygenation provides organ-specific assessment of perfusion. With understanding of the underlying principles of NIRS as well as the physiologic factors which impact oxygenation and perfusion of the brain, kidneys and bowel, changes in neonatal physiology can be more easily recognized by bedside providers, allowing for appropriate, targeted interventions. Amplitude-integrated electroencephalography (aEEG) allows continuous bedside evaluation of cerebral background activity patterns indicative of the level of cerebral function as well as identification of seizure activity. Normal background patterns are reassuring while abnormal background patterns indicate abnormal brain function. Combining brain monitoring information together with continuous vital sign monitoring (blood pressure, pulse oximetry, heart rate and temperature) at the bedside may be described as multi-modality monitoring and facilitates understanding of physiology. We describe 10 cases in critically ill neonates that demonstrate how comprehensive multimodal monitoring provided greater recognition of the hemodynamic status and its impact on cerebral oxygenation and cerebral function thereby informing treatment decisions. We anticipate that there are numerous other uses of NIRS as well as NIRS in conjunction with aEEG which are yet to be reported.

Neonates with hypoxic ischemic encephalopathy (HIE) are at significant risk for adverse outcomes including death and neurodevelopmental impairment. Neuromonitoring provides critical diagnostic and prognostic information for these infants. Modalities providing continuous monitoring include continuous electroencephalography (cEEG), amplitude-integrated electroencephalography (aEEG), near-infrared spectroscopy (NIRS), and heart rate variability. Serial bedside neuromonitoring techniques include cranial ultrasound and somatic and visual evoked potentials but may be limited by discrete time points of assessment. EEG, aEEG, and NIRS provide distinct and complementary information about cerebral function and oxygen utilization. Integrated use of these neuromonitoring modalities in addition to other potential techniques such as heart rate variability may best predict imaging outcomes and longer-term neurodevelopment. This review examines available bedside neuromonitoring techniques for the neonate with HIE in the context of therapeutic hypothermia.

Abstract Background Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO. Methods Newborns

Adequate oxygenation of the kidney is of critical importance in the neonate. Non-invasive monitoring of renal tissue oxygenation using near-infrared spectroscopy (NIRS) is a promising bedside strategy for early detection of circulatory impairment as well as recognition of specific renal injury. As a diagnostic tool, renal NIRS monitoring may allow for earlier interventions to prevent or reduce injury in various clinical scenarios in the neonatal intensive care unit. Multiple studies utilizing NIRS monitoring in preterm and term infants have provided renal tissue oxygenation values at different time points during neonatal hospitalization, and have correlated measures with ultrasound and Doppler flow data. With the establishment of normal values, studies have utilized renal tissue oxygenation monitoring in preterm neonates to predict a hemodynamically significant patent ductus arteriosus, to assess response to potentially nephrotoxic medications, to identify infants with sepsis, and to describe changes after red blood cell transfusions. Other neonatal populations being investigated with renal NIRS monitoring include growth restricted infants, those requiring delivery room resuscitation, infants with congenital heart disease, and neonates undergoing extracorporeal membrane oxygenation. Furthermore, as the recognition of acute kidney injury (AKI) and its associated morbidity and mortality in neonates has increased over the last decade, alternative methods are being investigated to diagnose AKI before changes in serum creatinine or urine output occur. Studies have utilized renal NIRS monitoring to diagnose AKI in specific populations, including neonates with hypoxic ischemic encephalopathy after birth asphyxia and in infants after cardiac bypass surgery. The use of renal tissue oxygenation monitoring to improve renal outcomes has yet to be established, but results of studies published to date suggest that it holds significant promise to function as a real time, early indicator of poor renal perfusion that may help with development of specific treatment protocols to prevent or decrease the severity of AKI.

Continuous brain monitoring tools are increasingly being used in the neonatal intensive care unit (NICU) to assess brain function and cerebral oxygenation in neonates at high risk for brain injury. Near infrared spectroscopy (NIRS) is useful in critically ill neonates as a trend monitor to evaluate the balance between tissue oxygen delivery and consumption, providing cerebral and somatic oximetry values, and allowing earlier identification of abnormalities in hemodynamics and cerebral perfusion. Amplitude-integrated electroencephalography (aEEG) is a method for continuous monitoring of cerebral function at the bedside. Simultaneous use of both monitoring modalities may improve the understanding of alterations in hemodynamics and risk of cerebral injury. Several studies have described correlations between aEEG and NIRS monitoring, especially in infants with hypoxic-ischemic encephalopathy (HIE), but few describe the combined use of both monitoring techniques in a wider range of clinical scenarios. We review the use of NIRS and aEEG in neonates and describe four cases where abnormal NIRS values were immediately followed by changes in brain activity as seen on aEEG allowing the impact of a hemodynamic disturbance on the brain to be correlated with the changes in the aEEG background pattern. These four clinical scenarios demonstrate how simultaneous neuromonitoring with aEEG and NIRS provides important clinical information. We speculate that routine use of these combined monitoring modalities may become the future standard for neonatal neuromonitoring.

We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NFκB). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NFκB translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NFκB translocation. However, NFκB regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI.