Pediatric Neurocritical Care

Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-011-0093-6) contains supplementary material, which is available to authorized users.     

Pediatric Neurocritical Care

Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.     

Emergency Neurological Life Support: Acute Ischemic Stroke

Neurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.     

Research and Technology in Neurocritical Care

The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.     

Multimodal monitoring and neurocritical care bioinformatics

Neurocritical care bioinformatics is a new field that focuses on the acquisition, storage and analysis of physiological and other data relevant to the bedside care of patients with acute neurological conditions such as traumatic brain injury or stroke. The main focus of neurocritical care for these conditions relates to prevention, detection and management of secondary brain injury, which relies heavily on monitoring of systemic and cerebral parameters (such as blood-pressure level and intracranial pressure). Advanced neuromonitoring tools also exist that enable measurement of brain tissue oxygen tension, cerebral oxygen utilization, and aerobic metabolism. The ability to analyze these advanced data for real-time clinical care, however, remains intuitive and primitive. Advanced statistical and mathematical tools are now being applied to the large volume of clinical physiological data routinely monitored in neurocritical care with the goal of identifying better markers of brain injury and providing clinicians with improved ability to target specific goals in the management of these patients. This Review provides an introduction to the concepts of multimodal monitoring for secondary brain injury in neurocritical care and outlines initial and future approaches using informatics tools for understanding and applying these data to clinical care.     

Cerebral Microdialysis in Neurocritical Care

Purpose of Review

A major goal in neurocritical care is to monitor for and prevent secondary brain injuries. However, injuries occurring at the cellular and molecular levels evade detection by conventional hemodynamic monitoring and the neurological exam. Cerebral microdialysis (CMD) is an invasive means of providing nearly continuous measurements of cerebral metabolism and is a promising tool that can detect signs of cellular distress before systemic manifestations of intracranial catastrophe.

Recent Findings

In this review, we describe the technique of CMD and the common biomarkers used to monitor cerebral energy metabolism. We examine the published evidence on how CMD data reflect secondary injuries and improve understanding of the pathophysiology of traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage. We also discuss some of the caveats of the technique, including how CMD probe position affect the sensitivity of capturing energy failures, and how abnormal levels of cerebral glucose and lactate can reflect different states of cerebral energy metabolism.

Summary

In order to best incorporate cerebral metabolic monitoring into the management of neurocritical care patients, neurointensivists must be familiar with the nuances in the limitations as well as the interpretations of data obtained from cerebral microdialysis.

     

Multimodal neuromonitoring for traumatic brain injury: A shift towards individualized therapy

Multimodal neuromonitoring in the management of traumatic brain injury (TBI) enables clinicians to make individualized management decisions to prevent secondary ischemic brain injury. Traditionally, neuromonitoring in TBI patients has consisted of a combination of clinical examination, neuroimaging and intracranial pressure monitoring. Unfortunately, each of these modalities has its limitations and although pragmatic, this simplistic approach has failed to demonstrate improved outcomes, likely owing to an inability to consider the underlying heterogeneity of various injury patterns. As neurocritical care has evolved, so has our understanding of underlying disease pathophysiology and patient specific considerations. Recent additions to the multimodal neuromonitoring platform include measures of cerebrovascular autoregulation, brain tissue oxygenation, microdialysis and continuous electroencephalography. The implementation of neurocritical care teams to manage patients with advanced brain injury has led to improved outcomes. Herein, we present a narrative review of the recent advances in multimodal neuromonitoring and highlight the utility of dedicated neurocritical care.     

Monitoring of Brain and Systemic Oxygenation in Neurocritical Care Patients

Maintenance of adequate oxygenation is a mainstay of intensive care, however, recommendations on the safety, accuracy, and the potential clinical utility of invasive and non-invasive tools to monitor brain and systemic oxygenation in neurocritical care are lacking. A literature search was conducted for English language articles describing bedside brain and systemic oxygen monitoring in neurocritical care patients from 1980 to August 2013. Imaging techniques e.g., PET are not considered. A total of 281 studies were included, the majority described patients with traumatic brain injury (TBI). All tools for oxygen monitoring are safe. Parenchymal brain oxygen (PbtO₂) monitoring is accurate to detect brain hypoxia, and it is recommended to titrate individual targets of cerebral perfusion pressure (CPP), ventilator parameters (PaCO₂, PaO₂), and transfusion, and to manage intracranial hypertension, in combination with ICP monitoring. SjvO₂ is less accurate than PbtO₂. Given limited data, NIRS is not recommended at present for adult patients who require neurocritical care. Systemic monitoring of oxygen (PaO₂, SaO₂, SpO₂) and CO₂ (PaCO₂, end-tidal CO₂) is recommended in patients who require neurocritical care.     

急性神经重症患者7天内进展为脑死亡的预测评分

目的构建急性神经重症患者在7 d内进展为脑死亡的预测评分,为此类患者的临床决策（姑息治疗或器官捐献）提供指导。 方法前瞻性纳入中山大学附属第一医院神经外科和重症医学科自2017年5月至2019年4月收治的急性神经重症患者,动态记录评估患者脑损伤的相关参数,依据入院时间将患者分为2组,训练集（2017年5月至2018年4月）和验证集（2018年5月至2019年4月）。在训练集中,以严重脑损伤（GCS<8分）发生后7 d,作为分组因素;通过单因素和多因素分析组间差异,筛选与急性神经重症患者在7 d内进展为脑死亡的相关因素,并进行Cox回归统计分析,构建曲线下面积（AUC）;构建神经学预测评分,并在验证集中验证评分效能。 结果纳入研究的患者231例,其中139例进入训练集,92例进入验证集。在训练集中,经单因素和多因素分析显示：气管插管行机械通气（OR=4.87,95%CI：1.36~17.35）、对光反射消失（OR=4.86,95%CI:1.75~33.92）、咳嗽反射消失（OR=4.43,95%CI：1.97~20.21）和中线结构移位≥5 mm（OR=3.82,95%CI：1.05~12.32）是患者7 d内进展为脑死亡独立危险因素。在验证集中,结果一致。基于相关因素构建的预测评分,其对于7 d内进展为脑死亡预测的AUC值为0.84。进一步对评分进行分层,其中4~6分对7 d内进展为脑死亡的阳性预测率为85.7%,而0~3分对7 d内不进展为脑死亡的阴性预测率为74.3%。 结论基于脑损伤评估参数构建的神经学评分,可预测急性神经重症患者进展为脑死亡的时间,结果有待外部数据验证。     

Cerebral hemodynamics: concepts of clinical importance

Cerebral hemodynamics and metabolism are frequently impaired in a wide range of neurological diseases, including traumatic brain injury and stroke, with several pathophysiological mechanisms of injury. The resultant uncoupling of cerebral blood flow and metabolism can trigger secondary brain lesions, particularly in early phases, consequently worsening the patient's outcome. Cerebral blood flow regulation is influenced by blood gas content, blood viscosity, body temperature, cardiac output, altitude, cerebrovascular autoregulation, and neurovascular coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and adenosine. A better understanding of these factors is valuable for the management of neurocritical care patients. The assessment of both cerebral hemodynamics and metabolism in the acute phase of neurocritical care conditions may contribute to a more effective planning of therapeutic strategies for reducing secondary brain lesions. In this review, the authors have discussed concepts of cerebral hemodynamics, considering aspects of clinical importance.     

Plateau Waves in Head Injured Patients Requiring Neurocritical Care

Object  

Plateau waves often develop in neurointensive care patients. They are sudden increases in intracranial pressure (ICP) that lead to dramatic decreases of cerebral perfusion pressure (CPP) and can therefore contribute to ischemic secondary brain insult. The aim of this study was to analyze the occurrence of plateau waves in head injured patients requiring neurocritical care, their relation with cerebral autoregulation and impact on outcome.     

Quo vadis 2010? - carpe diem: challenges and opportunities in pediatric traumatic brain injury

Traumatic brain injury (TBI) in infants and children remains a public health problem of enormous magnitude. It is a complex and heterogeneous condition that presents many diagnostic, therapeutic and prognostic challenges. A number of investigative teams are studying pediatric TBI both in experimental models and in clinical studies at the bedside. This review builds on work presented in a prior supplement to Developmental Neuroscience that was published in 2006, and addresses several active areas of research on this topic, including (1) the application of novel imaging methods, (2) the use of serum and/or CSF biomarkers of injury, (3) advances in neuromonitoring, (4) the development and testing of novel therapies, (5) developments in modeling pediatric TBI, (6) the consideration of a new approach to classification of pediatric TBI, and (7) assessing the potential impact of the development of pediatric and neonatal neurocritical care services on the management and outcome of pediatric TBI.     

Consistent Changes in Intracranial Pressure Waveform Morphology Induced by Acute Hypercapnic Cerebral Vasodilatation

Background  

Intracranial pressure (ICP) remains a pivotal physiological signal for managing brain injury and subarachnoid hemorrhage (SAH) patients in neurocritical care units. Given the vascular origin of the ICP, changes in ICP waveform morphology could be used to infer cerebrovascular changes. Clinical validation of this association in the setting of brain trauma, and SAH is challenging due to the multi-factorial influences on, and uncertainty of, the state of the cerebral vasculature.     

Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils

There is growing debate over the value of intensive insulin therapy (IIT) in critically ill patients. Available trials have been performed in general medical or surgical intensive care units, and the results may not be directly applicable to patients with severe acute brain disease because these patients may have heightened susceptibility to hyperglycemia (HyperG) and hypoglycemia. Our objective was to review the pathophysiology and effects of HyperG and hypoglycemia in neurocritical patients and to analyze the potential role of IIT in this population. Source data were obtained from a PubMed search of the medical literature combining the terms HyperG, hypoglycemia, insulin, stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), spinal cord injury (SCI), and related diagnoses. Brain metabolism is highly dependent on constant supply of glucose. As a consequence, the acutely injured brain is particularly sensitive to hypoglycemia, which can induce a state of energy failure (metabolic crisis). Meanwhile, neurocritical patients have a high prevalence of HyperG, and its occurrence is associated with poor outcome after acute ischemic stroke, ICH, SAH, and TBI. It is unclear whether this association is due to direct detrimental effects exerted by HyperG or simply represents a marker of severe brain injury. Insulin has been shown to have various potentially pleiotropic neuroprotective properties in experimental models. However, the safety and efficacy of IIT in patients with critical brain disease have not been well studied. Available results do not support the use of IIT to maintain strict normoglycemia in this population. Patients with critical brain disease should have frequent glucose monitoring because severe HyperG and even modest hypoglycemia may be detrimental. Careful use of insulin infusion protocols appears advisable, but maintenance of strict normoglycemia cannot be recommended. Rigorous studies must be conducted to assess the value of insulin therapy and to determine the optimal blood glucose targets in patients with the most common acute vascular and traumatic brain insults.

     

Antioxidant Strategies in Neurocritical Care

An increase in oxidative stress and overproduction of oxidizing reactive species plays an important role in the pathophysiology of several conditions encountered in the neurocritical care setting including: ischemic and hemorrhagic strokes, traumatic brain injury, acute respiratory distress syndrome, sepsis, and organ failure. The presence of oxidative stress in these conditions is supported by a large body of pre-clinical and clinical studies, and provides a rationale to support a potential therapeutic role for antioxidants. The purpose of this article is to briefly review the basic mechanisms and molecular biology of oxidative stress, summarize its role in critically ill neurological patients, and review available data regarding the potential role of antioxidant strategies in neurocritical care and future directions.     

Multimodality Monitoring Consensus Statement: Monitoring in Emerging Economies

The burden of disease and so the need for care is often greater at hospitals in emerging economies. This is compounded by frequent restrictions in the delivery of good quality clinical care due to resource limitations. However, there is substantial heterogeneity in this economically defined group, such that advanced brain monitoring is routinely practiced at certain centers that have an interest in neurocritical care. It also must be recognized that significant heterogeneity in the delivery of neurocritical care exists even within individual high-income countries (HICs), determined by costs and level of interest. Direct comparisons of data between HICs and the group of low- and middle-income countries (LAMICs) are made difficult by differences in patient demographics, selection for ICU admission, therapies administered, and outcome assessment. Evidence suggests that potential benefits of multimodality monitoring depend on an appropriate environment and clinical expertise. There is no evidence to suggest that patients in LAMICs where such resources exist should be treated any differently to patients from HICs. The potential for outcome benefits in LAMICs is arguably greater in absolute terms because of the large burden of disease; however, the relative cost/benefit ratio of such monitoring in this setting must be viewed in context of the overall priorities in delivering health care at individual institutions.     

Brain blood flow in the neurological determination of death: Canadian expert report

The neurological determination of death (NDD, brain death) is principally a clinical evaluation. However, ancillary testing is required when there are factors confounding the clinical determination or when it is impossible to complete the minimum clinical criteria. At the time of the 2003 Canadian Forum clarifying the criteria for brain death, 4-vessel cerebral angiography or radionuclide angiography were the recommended tests and the electroencephalogram was no longer supported. At the request of practitioners in the field, the Canadian Council for Donation and Transplantation sponsored the assembly of neuroradiology and neurocritical care experts to make further recommendations regarding the use of ancillary testing. At minimum, patients referred for ancillary testing should be in a deep unresponsive coma with an established etiology, in the absence of reversible conditions accounting for the unresponsiveness and the clinical examination should be performed to the fullest extent possible. For newborns, children and adults, demonstration of the absence of brain blood flow by following recommended imaging techniques fulfill the criteria for ancillary testing: 1. radionuclide angiography or CT angiography 2. traditional 4-vessel angiography 3. Magnetic resonance angiography or Xenon CT. In the absence of neuroimaging, an established cardiac arrest, as defined by the permanent loss of circulation, fulfills the ancillary criteria for the absence of brain blood flow. Acknowledging the existing limitations in this field, further research validating current or evolving techniques of brain blood flow imaging are recommended.     

Brain network markers of abnormal cerebral glucose metabolism and blood flow in Parkinson’s disease

Neuroimaging of cerebral glucose metabolism and blood flow is ideally suited to assay widely-distributed brain circuits as a result of local molecular events and behavioral modulation in the central nervous system. With the progress in novel analytical methodology, this endeavor has succeeded in unraveling the mechanisms underlying a wide spectrum of neurodegenerative diseases. In particular, statistical brain mapping studies have made significant strides in describing the pathophysiology of Parkinson’s disease (PD) and related disorders by providing signature biomarkers to determine the systemic abnormalities in brain function and evaluate disease progression, therapeutic responses, and clinical correlates in patients. In this article, we review the relevant clinical applications in patients in relation to healthy volunteers with a focus on the generation of unique spatial covariance patterns associated with the motor and cognitive symptoms underlying PD. These characteristic biomarkers can be potentially used not only to improve patient recruitment but also to predict outcomes in clinical trials.     

Global systems for monitoring cerebral hemodynamics in the neurocritical patient: basic concepts, controversies and recent advances in measuring jugular bulb oxygenation

Because of the importance of hypoxic/ischemic phenomena in head-injured patients, brain monitoring in these patients should be complemented by systems providing information on cerebral blood flow and metabolism. Indirect estimations of cerebral blood flow have been obtained from blood extracted from the jugular bulb, as a special bedside application of the Fick's principle to the brain. In the last few years, the use of jugular oximetry techniques has become routine in centers treating head-injured and other neurocritical patients such as those presenting subarachnoid hemorrhage or malignant middle cerebral artery infarction. The experience acquired in the use of these techniques, as well as the introduction of new neuromonitoring systems, have deepened our understanding of the information gained and have enabled more precise definition of their indications and limitations. This review describes the basic concepts underlying the use of jugular oximetry techniques in the neurocritical patient. We also explain the reasons why several variables derived from jugular blood such as arterio-jugular differences of lactate (AVDL) or the lactate-oxygen index (LOI) do not provide accurate information on brain metabolism.