ABSTRACT: 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.
Project description: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.
Project description:Pediatric neurocritical care is a growing subspecialty of pediatric intensive care that focuses on the management of acute neurological diseases in children. A brief history of the field of pediatric neurocritical care is provided. Neuromonitoring strategies for children are reviewed. Management of major categories of acute childhood central neurologic diseases are reviewed, including treatment of diseases associated with intracranial hypertension, seizures and status epilepticus, stroke, central nervous system infection and inflammation, and hypoxic-ischemic injury.
Project description:Disease-specific therapeutic options for critically ill neurological patients are limited. The identification of new preventive, therapeutic, and rehabilitation strategies is of the utmost importance in the field of neurocritical care research. Population genetics offers powerful tools to identify and prioritize biological pathways to be targeted by novel interventions. New treatments with supportive genetic evidence have twice the chances of obtaining final FDA approval compared to those without this support. Large collaborations, public access to data, reproducible science, and innovative analytical methods have exponentially increased the pace of discoveries related to neurocritical care genetics.
Project description:INTRODUCTION: Hyper- and hypoglycemia are strongly associated with adverse outcomes in critical care. Neurologically injured patients are a unique subgroup, where optimal glycemic targets may differ, such that the findings of clinical trials involving heterogeneous critically ill patients may not apply. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intensive insulin therapy with conventional glycemic control among patients with traumatic brain injury, ischemic or hemorrhagic stroke, anoxic encephalopathy, central nervous system infections or spinal cord injury. RESULTS: Sixteen RCTs, involving 1248 neurocritical care patients, were included. Glycemic targets with intensive insulin ranged from 70-140 mg/dl (3.9-7.8 mmol/L), while conventional protocols aimed to keep glucose levels below 144-300 mg/dl (8.0-16.7 mmol/L). Tight glycemic control had no impact on mortality (RR 0.99; 95% CI 0.83-1.17; p = 0.88), but did result in fewer unfavorable neurological outcomes (RR 0.91; 95% CI 0.84-1.00; p = 0.04). However, improved outcomes were only observed when glucose levels in the conventional glycemic control group were permitted to be relatively high [threshold for insulin administration > 200 mg/dl (> 11.1 mmol/L)], but not with more intermediate glycemic targets [threshold for insulin administration 140-180 mg/dl (7.8-10.0 mmol/L)]. Hypoglycemia was far more common with intensive therapy (RR 3.10; 95% CI 1.54-6.23; p = 0.002), but there was a large degree of heterogeneity in the results of individual trials (Q = 47.9; p<0.0001; I2 = 75%). Mortality was non-significantly higher with intensive insulin in studies where the proportion of patients developing hypoglycemia was large (> 33%) (RR 1.17; 95% CI 0.79-1.75; p = 0.44). CONCLUSIONS: Intensive insulin therapy significantly increases the risk of hypoglycemia and does not influence mortality among neurocritical care patients. Very loose glucose control is associated with worse neurological recovery and should be avoided. These results suggest that intermediate glycemic goals may be most appropriate.
Project description:The gold standard for assessing neurological function is the bedside clinical examination. However, in neurocritical patients, the signs and symptoms related to the severity of illness can often be ambiguous. It can be hard to distinguish between a severe but stable disease state and one that is dynamic and in a critical decline. Clinicians and family members alike may struggle with the uncertainty of functional outcome prediction. Intermediate biomarkers of brain injury can assist with ongoing clinical management of patients, and in some circumstances can guide prognosis. Used in the right setting, biomarkers in neurocritical care can also aid with decisions to intensify treatment or avoid prolonged and unnecessary therapy. The term biomarker is used in various ways, and here we use it to refer to 3 general types: 1) circulating blood macromolecules, 2) brain imaging, and 3) continuous invasive monitors. Despite its promise, biomarkers have several limitations and should be interpreted in the context of the overall clinical assessment.
Project description:The 2018 Paris Intensive Care symposium entitled "Update in Neurocritical Care" was organized in Paris, June 21-22, 2018, under the auspices of the French Intensive Care Society. This 2-day post-graduate educational symposium comprised several chapters, aiming first to provide all-board intensivists with current standards for the clinical assessment of altered consciousness states (including coma and delirium) and peripheral nervous system in critically ill patients, monitoring of brain function (specifically, electro-encephalography) and best practices for sedation-analgesia-delirium management. An update on the treatment of specific severe brain pathologies-including ischaemic/haemorrhagic stroke, cerebral venous thrombosis, hypoxic-ischaemic brain injury, immune-mediated and infectious encephalitis and refractory status epilepticus-was also provided. Finally, we discuss how to approach some difficult decisions, namely the role of decompressive craniectomy and prognostication models in patients with head injury. For each chapter, the scope of the present review was to provide important issues and key messages, provide most recent and relevant literature in the field, and briefly describe new developments in the field.
Project description:<h4>Introduction</h4>Neurocritical care is a rapidly developing subspecialty within intensive care medicine which aims to improve outcomes of critically ill neurological patients. This has inspired the formation of specialised intensive care units or services to provide dedicated care of brain-injured patients, as well as new training pathways for physicians. However, expansion has been variable worldwide and it is yet to be determined if there are clear benefits in regard to patient outcomes. We are planning a systematic review with meta-analysis to assess whether the introduction of neurocritical care units or services, or neurointensivists have favourable effects on survival.<h4>Methods and analysis</h4>We will include all observational and interventional studies comparing specialised neurocritical care units or services with general or non-specialised units in the care of acutely brain-injured adults. The primary outcome will be all-cause mortality at the longest follow-up, and secondary outcomes will be intensive care unit and hospital length of stay, and functional outcomes. All relevant studies will be identified through database searches. All study selection and data extraction will be conducted by two independent reviewers. We will conduct a random-effects meta-analysis to synthesise evidence for all outcomes. In addition, we will perform a subgroup analysis by disease process. We will assess confidence in the cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluations framework.<h4>Ethics and dissemination</h4>This systematic review and meta-analysis does not require ethical approval. We will publish findings from this systematic review in a peer-reviewed scientific journal and present these at conferences. It will be included in the primary author's higher degree research thesis.<h4>Prospero registration number</h4>CRD42020177190.
Project description:<h4>Objectives</h4>Targets for treatment of raised intracranial pressure or decreased cerebral perfusion pressure in pediatric neurocritical care are not well defined. Current pediatric guidelines, based on traumatic brain injury, suggest an intracranial pressure target of less than 20 mm Hg and cerebral perfusion pressure minimum of 40-50 mm Hg, with possible age dependence of cerebral perfusion pressure. We sought to define intracranial pressure and cerebral perfusion pressure thresholds associated with inhospital mortality across a large single-center pediatric neurocritical care cohort.<h4>Design</h4>Retrospective chart review.<h4>Setting</h4>PICU, single quaternary-care center.<h4>Patients</h4>Individuals receiving intracranial pressure monitoring from January 2012 to December 2016.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>Intracranial pressure and cerebral perfusion pressure measurements from 262 neurocritical care patients (87 traumatic brain injury and 175 nontraumatic brain injury; 63% male; 8.3 ± 5.8 yr; mortality 11.1%). Mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.75 and 0.64, respectively, for association of inhospital mortality. Cerebral perfusion pressure cut points increased with age (< 2 yr = 47, 2 to < 8 yr = 58 mm Hg, ≥ 8 yr = 73 mm Hg). In the traumatic brain injury subset, mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.70 and 0.78, respectively, for association of inhospital mortality. Traumatic brain injury cerebral perfusion pressure cut points increased with age (< 2 yr = 45, 2 to < 8 yr = 57, ≥ 8 yr = 68 mm Hg). Mean intracranial pressure greater than 15 mm Hg, male sex, and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 14.23 [5.55-36.46], 2.77 [1.04-7.39], and 2.57 [1.03-6.38], respectively; all p < 0.05). Mean cerebral perfusion pressure less than 67 mm Hg and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 5.16 [2.05-12.98] and 3.71 [1.55-8.91], respectively; both p < 0.01). In the nontraumatic brain injury subset, mean intracranial pressure had an area under the receiver operating characteristic curve 0.77 with an intracranial pressure cut point of 15 mm Hg, whereas mean cerebral perfusion pressure was not predictive of inhospital mortality.<h4>Conclusions</h4>We identified mean intracranial pressure thresholds, utilizing receiver operating characteristic and regression analyses, associated with inhospital mortality that is below current guidelines-based treatment targets in both traumatic brain injury and nontraumatic brain injury patients, and age-dependent cerebral perfusion pressure thresholds associated with inhospital mortality that were above current guidelines-based targets in traumatic brain injury patients. Further study is warranted to identify data-driven intracranial pressure and cerebral perfusion pressure targets in children undergoing intracranial pressure monitoring, whether for traumatic brain injury or other indications.
Project description:Brain injury is the leading cause of death in our pediatric ICU [Au et al. Crit Care Med 36:A128, 2008]. Clinical care for brain injury remains largely supportive. Therapeutic hypothermia has been shown to be effective in improving neurological outcome after adult ventricular-arrhythmia-induced cardiac arrest and neonatal asphyxia, and is under investigation as a neuroprotectant after cardiac arrest and traumatic brain injury in children in our ICU and other centers. To induce hypothermia in children comatose after cardiac arrest we target 32-34 degrees C using cooling blankets and intravenous iced saline as primary methods for induction, for 24-72 h duration with vigilant re-warming. The objective of this article is to share our hypothermia protocol for cooling children with acute brain injury.
Project description:BACKGROUND:Disorders requiring pediatric neurocritical care (PNCC) affect thousands of children annually. We aimed to quantify the burden of PNCC through generation of national estimates of disease incidence, utilization of critical care interventions (CCI), and hospital outcomes. METHODS:We performed a retrospective cohort analysis of the Kids Inpatient Database over three years to evaluate pediatric traumatic brain injury, neuro-infection or inflammatory diseases, status epilepticus, stroke, hypoxic ischemic injury after cardiac arrest, and spinal cord injury. We evaluated use of CCI, death, length of stay, hospital charges, and poor functional outcome defined as receipt of tracheostomy or gastrostomy or discharge to a medical care facility. RESULTS:At least one CCI was recorded in 67,058 (23%) children with a primary neurological diagnosis, and considered a PNCC admission. Over half of PNCC admissions had at least one chronic condition, and 23% were treated in children's hospitals. Mechanical ventilation was the most common CCI, but utilization of CCIs varied significantly by diagnosis. Among PNCC admissions, 8110 (12%) children died during hospitalization and 14,067 (21%) children had poor functional outcomes. PNCC admissions cumulatively accounted for over 1.5 million hospital days and over $4 billion in hospital costs in the study years. Most PNCC admissions, across all diagnoses, had prolonged hospitalizations (more than one week) with an average cost of $39.9 thousand per admission. CONCLUSIONS:This large, nationally representative study shows PNCC diseases are a significant public health burden with substantial risk to children's health. More research is needed to improve outcomes in these vulnerable children.