Neurology

Neonatology Questions and Controversies

Jeffrey M Perlman, Jeffrey Perlman

• Publisher: Elsevier
• Year: 2018
• eBook ISBN: 9780323568739
• Edition: 3
• Topic: Medicine
• Subtopic: Pediatric Medicine

Dr. Richard Polin's Neonatology Questions and Controversies series highlights the most challenging aspects of neonatal care, offering trustworthy guidance on up-to-date diagnostic and treatment options in the field. In each volume, renowned experts address the clinical problems of greatest concern to today's practitioners, helping you handle difficult practice issues and provide optimal, evidence-based care to every patient.- Stay fully up to date in this fast-changing field with Neurology, 3rd Edition.- The most current clinical information, including new coverage of genetics and pharmacology, early diagnosis and targeted treatment of neonatal-onset epilepsies, and the impact of congenital heart diseases on brain development.- Considerations of ongoing research regarding the basic mechanisms contributing to perinatal brain injury, which has in turn facilitated the introduction of targeted strategies in many areas.- Consistent chapter organization to help you find information quickly and easily.- The most authoritative advice available from world-class neonatologists who share their knowledge of new trends and developments in neonatal care. Purchase each volume individually, or get the entire 7-volume set!Gastroenterology and NutritionHematology, Immunology and GeneticsHemodynamics and CardiologyInfectious Disease and Pharmacology New Volume!Nephrology and Fluid/Electrolyte PhysiologyNeurologyThe Newborn Lung

Chapter 1

Cerebral Circulation and Hypotension in the Premature Infant

Diagnosis and Treatment

Shahab Noori, Claire McLean, Tai Wei-Wu, and Istvan Seri

Abstract

Despite advances in our understanding of developmental hemodynamics and our ability to better monitor the cardiovascular status in neonates, the definition of the “normal” gestational age– and postnatal age–dependent blood pressure range has remained an elusive target. In fact, as a blood pressure value may be associated with normal blood flow—and thus oxygen delivery in a given patient at a certain point in time—while the same value might represent an abnormal blood pressure associated with decreased blood flow and abnormal oxygen delivery at another time, it is likely that a universally applicable normal blood pressure range does not exist for neonates even with the same gestational and postnatal age. Therefore only with appropriate monitoring of blood pressure, blood flow, and tissue oxygen delivery in each neonate can the normal blood pressure be defined for the individual patient and the given point in time. With this background information in mind, this chapter describes the information available on systemic and cerebral blood flow and oxygenation in relation to systemic blood pressure and the characteristic cerebral pathologies seen in the neonate, and the information focuses on the transitional period. By examining the pathologic processes in relation to blood pressure and flow, the chance of designing and providing timely and potentially effective treatment becomes more realistic. We also describe a paradigm for treatment of the pathologic processes underlying clinically evident brain injury in the preterm infant. However, it must be emphasized that only little evidence exists on the safety and effectiveness of the presently used approaches to treatment of neonatal hypotension.

Keywords

cerebral autoregulation; cerebral circulation; hypotension; neonate; neonatal shock; neurodevelopment; periventricular/intraventricular hemorrhage; white matter injury

• Neonatal hypotension can be defined by population-based normative data, by the principles of developmental cardiovascular physiology (autoregulatory, functional and ischemic blood pressure thresholds) or by the pathophysiology (morbidity and/or mortality).

• During the immediate transitional period, a given blood pressure value at a given point in time in a given patient may be associated with normal systemic and organ blood flow. However, depending on the underlying cardiovascular pathology and the patient’s ability to compensate, the same blood pressure value in the same patient at a different time point may be associated with impaired systemic and organ blood flow and thus oxygen delivery.

• Only an association but not causation has been documented between hypotension and brain injury/poor neurodevelopmental outcome. Therefore at present, one cannot infer that long-term neurodevelopmental outcomes will improve if hypotension is rigorously avoided.

• Treatment of neonatal hypotension improves the major hemodynamic variables (blood pressure, cardiac output, organ blood flow and oxygen delivery) but improvement in neurodevelopmental outcomes has not yet been documented.

With the evolution of neonatology over the past few decades, improved methods of monitoring and more effective interventions have been developed to identify and manage the respiratory, fluid and electrolyte, and nutritional abnormalities frequently encountered in very low-birth-weight (VLBW) infants. However, the ability to effectively and continuously monitor the hemodynamic changes at the level of systemic and organ blood flow and tissue perfusion is still limited. Yet the advances achieved with the use of targeted neonatal echocardiography and other bedside monitoring devices providing noninvasive, continuous systemic, organ and tissue perfusion and cerebral function monitoring have started to usher in a new era in developmental hemodynamics. The novel monitoring modalities include but are not restricted to electrical impedance velocimetry, continuous wave Doppler ultrasonography, near-infrared spectroscopy (NIRS), visible light spectroscopy, laser Doppler technology, and amplitude-integrated electroencephalography (EEG, aEEG). Yet with the improvements in hemodynamic monitoring and a better understanding of the principles of developmental cardiovascular physiology have come the realization that little is known about circulatory compromise and its effects on organ function, especially brain blood flow, blood flow–metabolism coupling, and long-term outcomes. Although we can continuously and reliably monitor systemic blood pressure in absolute numbers and a great number of proposed interventions exist for “normalizing” it, blood pressure is only the dependent component among the three hemodynamic parameters regulating systemic perfusion. Accordingly, blood pressure is determined by changes in the two independent variables, cardiac output and systemic vascular resistance (SVR). Therefore in addition to monitoring and maintaining perfusion pressure (blood pressure), the goal is to preserve normal systemic and organ blood flow and thus tissue oxygenation especially in the vital organs—the brain, heart, and adrenal glands. In this regard, when it comes to the brain, medicine is at an even greater disadvantage. For instance, measuring cerebral blood flow (CBF) is more complex than continuously measuring systemic blood flow (left ventricular output), which itself has remained a significant challenge. Assessment of systemic blood flow becomes even more complicated when shunting through the fetal channels (ductus arteriosus and foramen ovale) occurs during the first few postnatal days in the preterm neonate. Unfortunately, it is more complicated to detect clinical evidence of ischemia in the brain in a timely manner in the neonate. In addition, distinct regions of the brain have different sensitivity to decreased oxygen delivery. Accordingly, injury to the normally less well-perfused white matter might occur before other regions suffer damage. Alterations in normal brain activity and seizures are clear signs of a pathologic process, but they can be difficult to recognize, especially in the VLBW neonate; although the use of aEEG might be helpful in this regard. As for seizures, by the time they are present, irreversible injury may have already occurred. Most importantly, the clinician faces the formidable task of effectively supporting and protecting the enormously complex developmental processes that take place in the brain of the preterm infant during the postnatal transitional period and beyond. In addition, the understanding of how to manage hemodynamic disturbances that affect CBF, flow-metabolism coupling, brain function and structure, and ultimately neurodevelopmental outcome is limited.

The intent of this chapter is to review the information available related to the definition of systemic hypotension as well as the pathogenesis, diagnosis, and treatment of early cerebral perfusion abnormalities that have been shown to precede intracranial hemorrhage and periventricular white matter injury (PWMI) in the VLBW infant. Because CBF flow-metabolism coupling and cerebral oxygenation in this population is complex, the discussion is focused on the first postnatal days, during which the cardiorespiratory transition from fetal to extrauterine life occurs and most pathologic processes take place. The discussion focuses on some bedside modalities potentially useful for identifying changes in CBF and cerebral oxygenation. In addition, a paradigm is presented for the treatment of the pathologic processes underlying clinically evident brain injury in the VLBW infant based on the most up-to-date monitoring and clinical evidence. Unfortunately, there is sparse evidence related to the appropriateness and effectiveness of current approaches to treatment of neonatal hypotension and cardiovascular compromise. The goal is to provide the practitioner with guidelines for establishing the diagnosis and treatment of neonatal hypotension. Finally, although the understanding of both the normal and pathologic processes in the developing preterm brain is improving, a definitive, safe, and effective clinical approach remains elusive.

Definition of Hypotension

Hypotension, defined by population-based normative data, is present in up to 50% of VLBW infants admitted to the neonatal intensive care unit. Hypotension in the immediate postnatal period has historically been thought to be one of the major factors contributing to central nervous system injury and poor long-term neurologic outcome, including cerebral palsy in VLBW neonates. Indeed, an association between hypotension and brain injury and poor neurodevelopmental outcome is well documented^1–9 and forms the basis of therapeutic efforts to normalize blood pressure. However, causation has not been demonstrated between hypotension and poor neurodevelopment and thus one cannot infer that long-term neurodevelopmental outcomes will improve if hypotension is rigorously avoided.¹⁰ Therein lies the conundrum often faced by the neonatologist: when to treat early cardiovascular compromise in the VLBW neonate, what medication to use, and how quickly to normalize blood pressure and CBF. Thus a prospective observational study of more than 1000 infants less than 28 weeks’ gestation showed that early postnatal hypotension was not associated with poorer outcomes.¹¹ Furthermore retrospective studies have raised additional concerns by demonstrating an association between “treated hypotension” and poor neurodevelopmental outcomes.^12–15 Of note, the use of the definition “treated hypotension” in these studies has introduced an additional bias by implying that, in addition to or independent of hypotension, the treatment might be a factor contributing to the described association. Although the implication of the potential negative effects ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Series Editor
• Copyright
• Contributors
• Preface
• Series Foreword
• Chapter 1. Cerebral Circulation and Hypotension in the Premature Infant: Diagnosis and Treatment
• Chapter 2. Intraventricular Hemorrhage and White Matter Injury in the Preterm Infant
• Chapter 3. Posthemorrhagic Hydrocephalus Management Strategies
• Chapter 4. Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Different Cooling Regimens and Infants Not Included in Prior Trials
• Chapter 5. General Supportive Management of the Term Infant With Neonatal Encephalopathy Following Intrapartum Hypoxia-Ischemia
• Chapter 6. Focal Cerebral Infarction
• Chapter 7. Diagnosis and Management of Acute Seizures in Neonates
• Chapter 8. Neonatal-Onset Epilepsies: Early Diagnosis and Targeted Treatment
• Chapter 9. Glucose and Perinatal Brain Injury—Questions and Controversies
• Chapter 10. Hyperbilirubinemia and the Risk for Brain Injury
• Chapter 11. Neonatal Meningitis: Current Treatment Options
• Chapter 12. Neonatal Herpes Simplex Virus, Congenital Cytomegalovirus, and Congenital Zika Virus Infections
• Chapter 13. Neonatal Hypotonia
• Chapter 14. Amplitude-Integrated EEG and Its Potential Role in Augmenting Management Within the NICU
• Chapter 15. Congenital Heart Disease: An Important Cause of Brain Injury and Dysmaturation
• Chapter 16. Long-Term Follow-Up of the Very Preterm Graduate
• Index