Severe Pediatric Traumatic Brain Injury Research Articles

Commentary: Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary

Department of Paediatric Neurosurgery, University of Cape Town, and Red Cross War Memorial Children's Hospital, Cape Town, South Africa Correspondence: Anthony Figaji, MD, PhD, 617 Institute for Child Health, Red Cross Childrens Hospital, Klipfontein Road, Rondebosch, Cape Town, Western Cape 7700, South Africa. Email: [email protected]

Commentary: Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary

Reisner, Andrew MD,,; Ralston, Ashley K MD,; Vats, Atul MD; Sawvel, Michael S DO; Blackwell, Laura S PhD Author Information

Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.

Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI. A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale. Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%). Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary.

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental appendices are available electronically (https://doi.org/10.1097/PCC.0000000000001735). The online documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

Fronto-temporal vulnerability to disconnection in paediatric moderate and severe traumatic brain injury.

In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales. Diffusion tensor (DT) and 3D T1-weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult=11.6years; 72.7% in chronic condition) and 31 age-matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRIindices were obtained from several supra- and infra-tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6months from the event) vs. chronic (≥6months) condition were performed. Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto-occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measurescores. The study isolated a distributed fronto-temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines: Erratum.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines: Erratum.

Plasma osteopontin may predict neuroinflammation and the severity of pediatric traumatic brain injury

Traumatic brain injury (TBI) is the leading cause of death in children and adolescents in developed countries, but there are no blood-based biomarkers to support the diagnosis or prognosis of pediatric TBI to-date. Here we report that the plasma levels of osteopontin (OPN), a phosphoprotein chiefly secreted by macrophages and/or activated microglia, may contribute to this goal. In animal models of TBI, while OPN, fibrillary acidic protein (GFAP), and matrix metalloproteinase 9 (MMP-9) were all readily induced by controlled cortical impact in the brains of one-month-old mice, only OPN and GFAP ascended in the blood in correlation with high neurological severity scores (NSS). In children with TBI (three to nine years of age, n = 66), the plasma levels of OPN, but not GFAP, correlated with severe TBI (Glasgow Coma Score ≤ 8) and intracranial lesions at emergency department. In addition, the plasma OPN levels in severe pediatric TBI patients continued to ascend for 72 h and correlated with mortality and the days requiring ventilator or intensive care unit support, whereas the plasma GFAP levels lacked these properties. Together, these results suggest that plasma OPN outperforms GFAP and may be a neuroinflammation-based diagnostic and prognostic biomarker in pediatric TBI.

Treatment of severe traumatic brain injury in German pediatric intensive care units-a survey of current practice.

German pediatric guidelines for severe traumatic brain injury (TBI) management expired in 2011. Thus, divergent evidence-based institutional protocols are predominantly being followed. We performed a survey of current Pediatric Intensive Care Unit (PICU) management of isolated severe TBI in Germany to reveal potential varying practices. Seventy German PICUs were invited to join an anonymous online survey from February to May 2017. Twenty-nine participants (41.4%) successfully completed the survey (17 university hospitals and 12 district hospitals). The majority of items were polar (yes/no) or scaled (e.g., never - always). Main topics were imaging, neurosurgery, neuromonitoring, adjuvant therapy, and medication. Severity of TBI was defined via Glasgow Coma Scale. The majority of respondents (93.1%) had internal TBI standards, and patients were mainly administered to interdisciplinary trauma units. The use of advanced neuromonitoring techniques, intracranial hypertension management, and drug treatment differed between PICUs. Routine administration of hypertonic saline in TBI-associated cerebral edema was performed by 3.4%, while it was never an option for 31.0% of the participants. Prophylactic anticonvulsive therapy was restrictively performed. If indicated, the main anticonvulsive drugs used were phenobarbital and levetiracetam. Neuroendocrine follow-up was recommended/performed by 58.6% of the PICUs. This survey provides an overview of the current PICU practices of isolated severe TBI management in Germany and demonstrates a wide instrumental and therapeutical range, revealing an unmet need for the revised national guideline and further (international) clinical trials for the treatment of severe TBI in pediatrics.

Management of Pediatric Severe Traumatic Brain Injury: 2019 Consensus and Guidelines-Based Algorithm for First and Second Tier Therapies.

To produce a treatment algorithm for the ICU management of infants, children, and adolescents with severe traumatic brain injury. Studies included in the 2019 Guidelines for the Management of Pediatric Severe Traumatic Brain Injury (Glasgow Coma Scale score ≤ 8), consensus when evidence was insufficient to formulate a fully evidence-based approach, and selected protocols from included studies. Baseline care germane to all pediatric patients with severe traumatic brain injury along with two tiers of therapy were formulated. An approach to emergent management of the crisis scenario of cerebral herniation was also included. The first tier of therapy focuses on three therapeutic targets, namely preventing and/or treating intracranial hypertension, optimizing cerebral perfusion pressure, and optimizing partial pressure of brain tissue oxygen (when monitored). The second tier of therapy focuses on decompressive craniectomy surgery, barbiturate infusion, late application of hypothermia, induced hyperventilation, and hyperosmolar therapies. This article provides an algorithm of clinical practice for the bedside practitioner based on the available evidence, treatment protocols described in the articles included in the 2019 guidelines, and consensus that reflects a logical approach to mitigate intracranial hypertension, optimize cerebral perfusion, and improve outcomes in the setting of pediatric severe traumatic brain injury.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary.

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, nine are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, three are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The purpose of publishing the algorithm as a separate document is to provide guidance for clinicians while maintaining a clear distinction between what is evidence based and what is consensus based. This approach allows, and is intended to encourage, continued creativity in treatment and research where evidence is lacking. Additionally, it allows for the use of the evidence-based recommendations as the foundation for other pathways, protocols, or algorithms specific to different organizations or environments. The complete guideline document and supplemental appendices are available electronically from this journal. These documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

Bifrontal Biparietal Cruciate Decompressive Craniectomy in Pediatric Traumatic Brain Injury

Background: We investigated a novel surgical approach to decompressive craniectomy (DC), the bifrontal biparietal, or “cruciate,” craniectomy, in severe pediatric traumatic brain injury (TBI). Cruciate DC was designed with a fundamentally different approach to intracranial pressure (ICP) control compared to traditional DC. Cruciate DC involves craniectomies in all 4 skull quadrants. The sagittal and coronal bone struts are disarticulated at the skull to allow the decompression of the sagittal sinus and bridging veins in addition to permitting cerebral expansion, thereby maintaining cranial compliance. Objective: To characterize ICP control with cruciate DC in pediatric TBI. Methods: We performed a retrospective review of TBI patients who underwent cruciate DC. We investigated mortality and preoperative and postoperative ICP. Group 1 underwent medical therapy prior to DC and Group 2 required immediate DC. Results: Fifteen of 18 patients survived. In Group 1, mean preoperative ICP was 18.5 mm Hg and mean postoperative ICP was 11.5 mm Hg. In Group 2, mean preoperative ICP was 27.3 mm Hg and mean postoperative ICP was 15.0 mm Hg. Conclusion: Cruciate DC was associated with lowering ICP. We observed acute drops in ICP and long-term ICP control. The floating bone struts of the cruciate DC permits the decompression of the sagittal sinus and bridging veins, with maximal relief of cerebral edema.

Use of magnetic resonance imaging in severe pediatric traumatic brain injury: assessment of current practice.

There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.

Nonaccidental Trauma Associated with Withdrawal of Care in Severe Pediatric Traumatic Brain Injury

Grigorian, Areg MD; de Virgilio, Christian MD, FACS; Lekawa, Michael E. MD; Ramakrishnan, Divya; Barros, Rebecca MD; Kuncir, Eric J. MD, FACS; Nahmias, Jeffry MD, MHPE Author Information

Combining Brain Microdialysis and Translational Pharmacokinetic Modeling to Predict Drug Concentrations in Pediatric Severe Traumatic Brain Injury: The Next Step Toward Evidence-Based Pharmacotherapy?

Evidence-based analgosedation in severe pediatric traumatic brain injury (pTBI) management is lacking, and improved pharmacological understanding is needed. This starts with increased knowledge of factors controlling the pharmacokinetics (PK) of unbound drug at the target site (brain) and related drug effect(s). This prospective, descriptive study tested a pediatric physiology-based pharmacokinetic software model by comparing actual plasma and brain extracellular fluid (brainECF) morphine concentrations with predicted concentration-time profiles in severe pTBI patients (Glasgow Coma Scale [GCS], ≤8). Plasma and brainECF samples were obtained after legal guardian written consent and were collected from 8 pTBI patients (75% male; median age, 96 months [34.0-155.5]; median weight, 24 kg [14.5-55.0]) with a need for intracranial pressure monitoring (GCS, ≤8) and receiving continuous morphine infusion (10-40 μg/kg/h). BrainECF samples were obtained by microdialysis. BrainECF samples were taken from "injured" and "uninjured" regions as determined by microdialysis catheter location on computed head tomography. A previously developed physiology-based software model to predict morphine concentrations in the brain was adapted to children using pediatric physiological properties. The model predicted plasma morphine concentrations well for individual patients (97% of data points within the 90% prediction interval). In addition, predicted brainECF concentration-time profiles fell within a 90% prediction interval of microdialysis brainECF drug concentrations when sampled from an uninjured area. Prediction was less accurate in injured areas. This approach of translational physiology-based PK modeling allows prediction of morphine concentration-time profiles in uninjured brain of individual patients and opens promising avenues towards evidence-based pharmacotherapies in pTBI.

Pre-Trauma Center Management of Intracranial Pressure in Severe Pediatric Traumatic Brain Injury.

Pre-trauma center care is a critical component in severe pediatric traumatic brain injury (TBI). For geographically large trauma catchment areas, optimizing increased intracranial pressure (ICP) management may potentially improve outcomes. This retrospective study examined ICP management in nontrauma centers and during interfacility transport to the trauma center. Charts from a pediatric level I trauma center were reviewed for admissions between 2008 and 2013. Patients with a Glasgow Coma Scale score of 8 or less, head Abbreviated Injury Scale score of 3 or higher, and requiring intubation at a nontrauma center were included. Exclusion criteria included head injury secondary to drowning, stroke, obstetrical complications, asphyxia, and afflicted head trauma (younger than 5 years). Trauma center charts contained coalesced data from first responders, nontrauma centers, and transport. Twenty-five patients (74%) had increased ICP upon admission at trauma center, 48% experienced ICPs greater than 20 cm H2O within 12 hours of admission, 12% required an urgent craniotomy, and 16% had herniation syndromes on neuroimaging. Pre-trauma center ICP management included osmotherapy and head-of-bed elevation. Sixty-four percent of patients with increased ICP at trauma center admission received pre-trauma center ICP management. Early increased ICP is a common presentation of severe pediatric TBI during pre-trauma center management. However, what constitutes optimal care remains unknown. Given the difficulties of diagnosing early increased ICP in this setting, prophylactic raising ICP-lowering strategies may be considered.

The Influence of Presenting Characteristics on Outcomes in Moderate to Severe Pediatric Traumatic Brain Injury: Penetrating versus Blunt Mechanisms (P3.295)

The Influence of Presenting Characteristics on Outcomes in Moderate to Severe Pediatric Traumatic Brain Injury: Penetrating versus Blunt Mechanisms (P3.295)

Simulation of the Emergency Department Care Process for Pediatric Traumatic Brain Injury.

The treatment of patients in the emergency department (ED) with severe pediatric traumatic brain injury (TBI) is challenging, and treatment process strategies that facilitate good outcomes are not well documented. The overall objective of this study was to identify factors that can affect the care process associated with pediatric TBI. This objective was achieved using a discrete-event simulation model of patients with TBI as they progress through the ED treatment process of a Level I trauma center. This model was used to identify areas where the ED length of stay can be reduced. The number of patients arriving at any given time was also varied in the simulation model to observe the impact to bed allocation policies and changes in staff and equipment. The findings showed that implementing changes in the ED (i.e., availability of two computerized tomography scanners, formation of resuscitation teams that included eight staff personnel, and modifying the bed allocation policy) could result in a 17% reduction in the mean ED length of stay. The study outcomes would be of interest to those (e.g., health administrators, health managers, and physicians) who can make decisions related to the treatment process in an ED.

Multimodality neuromonitoring in severe pediatric traumatic brain injury.

Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the United States are 57.7 per 100K in the <5 years of age and 23.1 per 100K in the 5-14 years age group. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Historically, TBI management has been guided by clinical examination. This has been assisted progressively by clinical imaging, intracranial pressure (ICP) monitoring, and finally a software that can calculate optimal brain physiology. Multimodality monitoring affords clinicians an early indication of secondary insults to the recovering brain including raised ICP and decreased cerebral perfusion pressure. From variables such as ICP and arterial blood pressure, correlations can be drawn to determine parameters of cerebral autoregulation (pressure reactivity index) and "optimal cerebral perfusion pressure" at which the vasculature is most reactive. More recently, significant advances using both direct and near-infrared spectroscopy-derived brain oxygenation plus cerebral microdialysis to drive management have been described. Here in, we provide a perspective on the state-of-the-art techniques recently implemented in clinical practice for pediatric TBI.

Examining Emergency Department Treatment Processes in Severe Pediatric Traumatic Brain Injury.

In the treatment of pediatric traumatic brain injury (TBI), timely treatment of patients can affect the outcome. Our objectives were to examine the treatment process of acute pediatric TBI and the impact of non-value-added time (NVAT) on patient outcomes. Data for 136 pediatric trauma patients (age < 18 years) with severe TBI from 2 trauma centers in the United States were collected. A process flow and value stream map identified NVATs and their sources in the treatment process. Cluster and regression analysis were used to examine the relationship between NVAT, as a percentage of the patient's length of stay (LOS), and the patient outcome, measured by their corresponding Glasgow outcome scale. There were 14 distinct sources of NVAT identified. A regression analysis showed that increased NVAT was associated with less favorable outcomes (relative ratio = 1.015, confidence interval = [1.002-1.029]). Specifically, 1% increase in the NVAT-to-LOS ratio was associated with a 1.5% increase in the chance of a less favorable outcome (i.e., death or vegetative state). The NVAT has a significant impact on the outcome of pediatric TBI, and every minute spent on performing non-value-added processes can lead to an increase in the likelihood of less favorable outcomes.