Clinical Epidemiology of Extracranial Injuries in Severe Pediatric Traumatic Brain Injury in South America.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of pediatric mortality, with a disproportionate burden on low- and middle-income countries. The impact of concomitant extracranial injury (ECI) on these patients remains unclear. This study is the first to characterize the epidemiology and clinical course of severe pediatric TBI with extracranial injuries in any South American country. METHODS: We conducted a secondary analysis of baseline data collected prior to implementation of a clinical trial on TBI care in Argentina, Paraguay, and Chile from September 2019 to July 2020. Patients ≤18 years with CT evidence of TBI, and a Glasgow coma scale (GCS) score ≤8 were recruited. Patients were initially stratified by highest non-head abbreviated injury scale (AIS): isolated TBI (AIS=0), minor extracranial injury (MEI; AIS=1-2), and serious extracranial injury (SEI; AIS≥3). Patients were subsequently stratified by mechanism of injury. Intergroup differences were compared using ANOVA, two-tailed unpaired t-tests, and chi-square tests. RESULTS: Among the 116 children included, 33 % (n = 38) had an isolated TBI, 34 % (n = 39) had MEI, and 34 % (n = 39) had SEI. Facial (n = 53), thoracic (n = 44), and abdominal (n = 31) injuries were the most common ECIs. At discharge, there were no significant differences in median GCS, GOS, or GOS-extended between groups. Patients with SEI had a longer hospital LOS than those with isolated TBI (median 28.0 (IQR 10.6-40.1) vs 11.9 (IQR 8.7-20.7) days, p = 0.013). The most common mechanisms of injury were road traffic injuries (RTIs) (n = 50, 43 %) and falls (n = 35, 30 %). Patients with RTI-associated TBIs were more likely to be older (median 11.0 (IQR 3.0-14.0) vs 2.0 (IQR 0.8-7.0) years, p<0.001) and more likely to have an ECI (86% vs 54 %, respectively; p = 0.003). ICU and Hospital LOS for RTI patients (median 10.5 (IQR 6.1-21.1) and 24.1 (IQR 11.5-40.4) days) were longer than those of fall patients (median 6.1 (IQR 2.6-8.9) and 13.7 (IQR 7.7-24.5) days). CONCLUSIONS: Extracranial injuries are common in South American patients with severe TBI. Severe ECI is more frequently associated with RTIs and can result in a higher rate of surgical procedures and LOS. Further strategies are needed to characterize the prevention and treatment of severe pediatric TBI in the South American context.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

OBJECTIVES: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051). CONCLUSIONS: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

The Pediatric Guideline Adherence and Outcomes (PEGASUS Argentina) program in severe traumatic brain injury: study protocol adaptations during the COVID-19 pandemic for a multisite implementation-effectiveness cluster randomized controlled trial.

BACKGROUND: The aim of this protocol is to describe the study protocol changes made and subsequently implemented to the Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina randomized controlled trial (RCT) for care of children with severe traumatic brain injuries (TBI) imposed by the COVID-19 pandemic. The PEGASUS study group met in spring 2020 to evaluate available literature review guidance and the study design change or pausing options due to the potential interruption of research. METHODS: As a parallel cluster RCT, pediatric patients with severe TBIs are admitted to 8 control (usual care) and 8 intervention (PEGASUS program) hospitals in Argentina, Chile, and Paraguay. PEGASUS is an intervention that aims to increase guideline adherence and best practice care for improving patient outcomes using multi-level implementation science-based approaches. Strengths and weaknesses of proposed options were assessed and resulted in a decision to revert from a stepped wedge to a parallel cluster RCT but to not delay planned implementation. DISCUSSION: The parallel cluster design was considered more robust and flexible to secular interruptions and acceptable and feasible to the local study sites in this situation. Due to the early stage of the study, the team had flexibility to redesign and implement a design more compatible with the conditions of the research landscape in 2020 while balancing analytical methods and power, logistical and implementation feasibility, and acceptability. As of fall 2022, the PEGASUS RCT has been active for nearly 2 years of implementation and data collection, scheduled to be completed in in fall 2023. The experience of navigating research during this period will influence decisions about future research design, strategies, and contingencies. TRIAL REGISTRATION: Pediatric Guideline Adherence and Outcomes-Argentina. Registered with ClinicalTrials.gov Identifier NCT03896789 on April 1, 2019.

The Temporal Association of the COVID-19 Pandemic and Pediatric Cardiopulmonary Resuscitation Quality and Outcomes.

OBJECTIVES: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. DESIGN: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04). CONCLUSIONS: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

Provider perceptions of severe pediatric traumatic brain injury care priorities across hospitals in South America before and during the COVID-19 pandemic.

BACKGROUND: To understand provider perceptions of the COVID-19 pandemic on priorities of severe pediatric traumatic brain injury (TBI) care across hospitals in South America. METHODS: Site principal investigators (PIs) from 17 hospitals in South America enrolled in the PEGASUS-Argentina randomized controlled trial completed questionnaires regarding order of tasks performed in the care of a typical pediatric patient with severe TBI before (2019) and during (2021) the COVID-19 pandemic. Acute care processes were examined by quintiles to identify early, mid, and late actions and were categorized and compared. Associations of hospital volume and subspecialty resource availability with prioritization of key process actions were examined. FINDING: Site PIs from 15 and 16 hospitals completed the surveys in 2019 and 2021, respectively, including 14 who completed both. Action category order was stable between 2019 and 2021 and were ranked in priorities as: initial encounter, primary survey, interventions and invasive monitors, diagnostics, medications, staff communication, then disposition (in 2019) or nutrition (in 2021). There was variation in specific action order between hospitals at both timepoints, with only a few initial encounter and disposition actions limited to a single quintile. There was no reported association between hospital volume or subspecialty resource availability with prioritization of key process actions. INTERPRETATION: Despite novel healthcare challenges presented by the COVID-19 pandemic, providers in South America perceived maintaining standard severe pediatric TBI care consistent with BTF guidelines. There was large variability in specific action order between individual hospitals reported.

Temporal and Spatial Changes in the Microbiome Following Pediatric Severe Traumatic Brain Injury.

OBJECTIVES: The microbiome may be affected by trauma and critical illness. Many studies of the microbiome in critical illness are restricted to a single body site or time point and confounded by preexisting conditions. We report temporal and spatial alterations in the microbiome of previously healthy children with severe traumatic brain injury (TBI). DESIGN: We collected oral, rectal, and skin swabs within 72 hours of admission and then twice weekly until ICU discharge. Samples were analyzed by 16S rRNA gene amplicon sequencing. Children undergoing elective outpatient surgery served as controls. Alpha and beta diversity comparisons were performed with Phyloseq, and differentially abundant taxa were predicted using Analysis of Composition of Microbiomes. SETTING: Five quaternary-care PICUs. PATIENTS: Patients less than 18 years with severe TBI requiring placement of an intracranial pressure monitor. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred twenty-seven samples were analyzed from 23 children with severe TBI and 35 controls. The community composition of initial oral (F = 3.2756, R2 = 0.0535, p = 0.012) and rectal (F = 3.0702, R2 = 0.0649, p = 0.007) samples differed between TBI and control patients. Rectal samples were depleted of commensal bacteria from Ruminococcaceae, Bacteroidaceae, and Lachnospiraceae families and enriched in Staphylococcaceae after TBI (p < 0.05). In exploratory analyses, antibiotic exposure, presence of an endotracheal tube, and occurrence of an infection were associated with greater differences of the rectal and oral microbiomes between TBI patients and healthy controls, whereas enteral nutrition was associated with smaller differences (p < 0.05). CONCLUSIONS: The microbiome of children with severe TBI is characterized by early depletion of commensal bacteria, loss of site specificity, and an enrichment of potential pathogens. Additional studies are needed to determine the impact of these changes on clinical outcomes.

The Status of Quality Improvement Programs for Pediatric Traumatic Brain Injury Care in Argentina.

INTRODUCTION: Trauma quality improvement (QI) programs improve care and outcomes for injured patients. Information about QI programs for pediatric traumatic brain injury (TBI) is sparse in Latin America. METHODS: We gathered data on the status of QI programs and activities that encompass pediatric TBI at 15 Argentine hospitals. Data were gathered during 2019 and included hospital characteristics, QI practices, presence of a queryable registry, and use of protocols for TBI care. Level of QI activities was compared between hospital types using Fisher's exact test. RESULTS: Most hospitals had guidelines for pediatric TBI care, including management and/or prevention of intracranial pressure (100%) and central-line-associated infections (87%). Morbidity and mortality meetings or other types of case discussions in which quality of pediatric TBI care was discussed were held by all hospitals, with most (53%) having weekly-monthly meetings, but 27% having rare or annual meetings. Sixty percent of hospitals had adequate data for case reviews (fewer than 25% of cases with essential information missing). Fifty-three percent documented discussions that occurred at these meetings and 53% utilized computerized trauma registries. Larger hospitals (> 200 beds) more frequently had adequate data (88%) for case reviews than smaller hospitals (29%, P = 0.046). Hospital size did not affect other QI activities. CONCLUSIONS: Most hospitals had guidelines for pediatric TBI care. Adequacy of care was discussed at reasonably frequent case conferences. Opportunities for improvement include increasing documentation of case reviews and improving adequacy of data for case reviews, especially at smaller hospitals. Greater use of computerized trauma registries could provide such data.

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

OBJECTIVES: To produce a treatment algorithm for the ICU management of infants, children, and adolescents with severe traumatic brain injury. DATA SOURCES: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To identify injury patterns and characteristics associated with severe traumatic brain injury course and outcome, within a well-characterized cohort, which may help guide new research and treatment initiatives. DESIGN: A secondary analysis of a phase 3, randomized, controlled trial that compared therapeutic hypothermia versus normothermia following severe traumatic brain injury in children. SETTING: Fifteen sites in the United States, Australia, and New Zealand. PATIENTS: Children (< 18 yr old) with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Baseline, clinical, and CT characteristics of patients (n = 77) were examined for association with mortality and outcome, as measured by the Glasgow Outcome Scale-Extended Pediatric Revision 3 months after traumatic brain injury. Data are presented as odds ratios with 95% CIs. No demographic, clinical, or CT characteristic was associated with mortality in bivariate analysis. Characteristics associated with worse Glasgow Outcome Scale-Extended Pediatric Revision in bivariate analysis were two fixed pupils (14.17 [3.38-59.37]), abdominal Abbreviated Injury Severity score (2.03 [1.19-3.49]), and subarachnoid hemorrhage (3.36 [1.30-8.70]). Forward stepwise regression demonstrated that Abbreviated Injury Severity spine (3.48 [1.14-10.58]) and midline shift on CT (8.35 [1.05-66.59]) were significantly associated with mortality. Number of fixed pupils (one fixed pupil 3.47 [0.79-15.30]; two fixed pupils 13.61 [2.89-64.07]), hypoxia (5.22 [1.02-26.67]), and subarachnoid hemorrhage (3.01 [1.01-9.01]) were independently associated with worse Glasgow Outcome Scale-Extended Pediatric Revision following forward stepwise regression. CONCLUSIONS: Severe traumatic brain injury is a clinically heterogeneous disease that can be accompanied by a range of neurologic impairment and a variety of injury patterns at presentation. This secondary analysis of prospectively collected data identifies several characteristics associated with outcome among children with severe traumatic brain injury. Future, larger trials are needed to better characterize phenotypes within this population.

Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury.

OBJECTIVES: To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment. DESIGN: Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board-approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009). SETTING: Thirty-six-bed PICU in a university-affiliated children's hospital. PATIENTS AND SUBJECTS: Twelve children 2-18 years old after severe traumatic brain injury and five age-matched control subjects. INTERVENTION: Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube. MEASUREMENTS AND MAIN RESULTS: The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation. CONCLUSIONS: This proof-of-concept neuropharmacometabolomics assessment reveals alterations in known and previously unidentified metabolic pathways and supports therapeutic target engagement of the combination of probenecid and N-acetylcysteine treatment after severe traumatic brain injury in children.

Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To understand the relationship between the timing of initiation of nutritional support in children with severe traumatic brain injury and outcomes. DESIGN: Secondary analysis of a randomized, controlled trial of therapeutic hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known as "the Cool Kids Trial" (NCT 00222742). SETTINGS: Fifteen clinical sites in the United States, Australia, and New Zealand. SUBJECTS: Inclusion criteria included 1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be randomized within 6 hours after injury. Exclusion criteria included normal head CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (< fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability of a parent or guardian to consent at centers without emergency waiver of consent. INTERVENTIONS: Therapeutic hypothermia (32-33°C for 48 hr) followed by slow rewarming for the primary study. For this analysis, the only intervention was the extraction of data regarding nutritional support from the existing database. MEASUREMENTS AND MAIN RESULTS: Timing of initiation of nutritional support was determined and patients stratified into four groups (group 1-no nutritional support over first 7 d; group 2-nutritional support initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72 hr after injury; group 4-nutritional support initiated 72-168 hr after injury). Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed to define the relationship between nutrition and outcome. Children (n = 90, 77 randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of nutrition before 72 hours was associated with survival (p = 0.01), favorable 6 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable 12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04). Specifically, groups 2 and 3 had favorable outcomes versus group 1. CONCLUSIONS: Initiation of nutritional support before 72 hours after traumatic brain injury was associated with decreased mortality and favorable outcome in this secondary analysis. Although this provides a rationale to initiate nutritional support early after traumatic brain injury, definitive studies that control for important covariates (severity of injury, clinical site, calories delivered, parenteral/enteral routes, and other factors) are needed to provide definitive evidence on the optimization of the timing of nutritional support after severe traumatic brain injury in children.

Intensive care treatments associated with favorable discharge outcomes in Argentine children with severe traumatic brain injury: For the South American Guideline Adherence Group.

OBJECTIVE: Little is known about the critical care management of children with traumatic brain injury (TBI) in low middle income countries. We aimed to identify indicators of intensive care unit (ICU) treatments associated with favorable outcomes in Argentine children with severe TBI. METHODS: We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with severe TBI who were admitted to an ICU in one of the seven study centers. Severe TBI was defined by head AIS ≥ 3, head CT with traumatic lesion, and admission GCS < 9. Seven indicators of best practice TBI care were examined. The primary outcome was discharge Pediatric Cerebral Performance Category Scale [PCPC] and Pediatric Overall Performance category Scale [POPC]. We also examined variation in ICU care and in-patient mortality. RESULTS: Of the 117 children, 67% were male and 7.5 (4.3) years on average, 92% had isolated TBI. Hypotension (54%) was more common than hypoxia (28%) and clinical or radiographic signs of high intracranial pressure (ICP) were observed in 92%. Yet, ICP monitoring occurred in 60% and hyperosmolar therapy was used in only 36%. Adherence to indicators of best TBI practice ranged from 55.6% to 83.7% across the seven centers and adherence was associated with favorable discharge PCPC (aRR 0.98; 95% CI [0.96, 0.99]), and POPC (aRR 0.98; 95% CI [0.96, 0.99]). Compared to patients whose adherence rates were below 65%, patients whose adherence rates were higher between 75%-100% had better discharge PCPC (aRR 0.28; 95% CI [0.10, 0.83]) and POPC (aRR 0.32; 95% CI [0.15, 0.73]. Two indicators were associated with favorable discharge PCPC: Avoidance of hypoxia (aRR 0.46; 95% CI [0.23, 0.93]), and Nutrition started in 72 hours (aRR 0.45; 95% CI [0.21, 0.99]). Avoiding hypoxia was also associated with favorable discharge POPC (aRR 0.47; 95% CI [0.22, 0.99]). CONCLUSION: There is variation in Argentine ICU practice in the care of children with severe TBI. Second insults are common and hyperosmolar therapy use is uncommon. Adherence to best practice TBI care by avoiding hypoxia and providing timely nutrition were associated with significantly favorable discharge outcomes. Implementing strategies that prevent hypoxia and facilitate early nutrition in the ICUs are urgently needed to improve pediatric TBI outcomes.

Benchmarking Prehospital and Emergency Department Care for Argentine Children with Traumatic Brain Injury: For the South American Guideline Adherence Group.

OBJECTIVE: There is little information on the type of early care provided to children with traumatic brain injury (TBI) in low middle income countries. We benchmarked early prehospital [PH] and emergency department [ED] pediatric TBI care in Argentina. METHODS: We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with TBI. Eligible participants were patients 0-18 years, and had diagnosis of TBI (admission Glasgow Coma scale score [GCS] < 13 or with GCS 14-15 and abnormal head CT scan within 48 hours of admission, and head AIS > 0). Outcomes were transport type, transport time, PH and ED adherence to best practice, and discharge Pediatric Cerebral Performance Category Scale (PCPC) and Pediatric Overall Performance category Scale (POPC). RESULTS: Of the 366 children, mean age was 8.7 (5.0) years, 58% were male, 90% had isolated TBI and 45.4% were transported by private vehicle. 50 (34.7%) of the 144 children with severe TBI (39.3% of all TBI patients) were transported by private vehicle. Most (267; 73%) patients received initial TBI care at an index hospital prior to study center admission, including children with severe (81.9%) TBI. Transport times were shorter for those patients who were directly transported by ambulance to study center than for the whole cohort (1.4 vs.5.5 hours). Ambulance blood pressure data were recorded in 30.9%. ED guideline adherence rate was higher than PH guideline adherence rate (84.8% vs. 26.4%). For patients directly transferred from scene to study trauma centers, longer transport time was associated with worse discharge outcome (PCPC aOR 1.10 [1.04, 1.18] and (POPC aOR 1.10 [1.04, 1.18]). There was no relationship between PH or ED TBI guideline adherence rate and discharge POPC and PCPC. CONCLUSION: This study benchmarks early pediatric TBI care in Argentina and shows that many critically injured children with TBI do not receive timely or best practice PH care, that PH guideline adherence rate is low and that longer transport time was associated with poor discharge outcomes for patients with direct transfer status. There is an urgent need to improve the early care of children with TBI in Argentina, especially timely transportation to a hospital.

Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study.

OBJECTIVES: Early posttraumatic seizures may contribute to worsened outcomes after traumatic brain injury. Evidence to guide the evaluation and management of early posttraumatic seizures in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring, seizure prophylaxis, and the management of early posttraumatic seizures to provide essential information for trial design and the development of posttraumatic seizure management pathways. DESIGN: Surveys were sent to site principal investigators at all 43 sites participating in the Approaches and Decisions in Acute Pediatric TBI trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to 1) implement continuous electroencephalographic monitoring, 2) posttraumatic seizure prophylaxis, 3) treat acute posttraumatic seizures, 4) treat status epilepticus and refractory status epilepticus, and 5) monitor antiseizure drug levels. SETTING: Institutions comprised a mixture of free-standing children's hospitals and university medical centers across the United States and Europe. SUBJECTS: Site principal investigators of the Approaches and Decisions in Acute Pediatric TBI trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalographic monitoring was available in the PICU in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic antiseizure medications is anticipated in children (93%); yet, a minority reports that a specified protocol for treatment of posttraumatic seizures is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for refractory status epilepticus (81%). The presence of treatment protocols for seizure prophylaxis, early posttraumatic seizures, posttraumatic status epilepticus, and refractory status epilepticus was associated with decreased reported medications (all p < 0.05). CONCLUSIONS: This study reports the current management practices for early posttraumatic seizures in select academic centers after pediatric severe traumatic brain injury. The substantial variation in continuous electroencephalographic monitoring implementation, choice of seizure prophylaxis medications, and management of early posttraumatic seizures across institutions was reported, signifying the areas of clinical uncertainty that will help provide focused design of clinical trials. Although sites with treatment protocols reported a decreased number of medications for the scenarios described, completion of the Approaches and Decisions in Acute Pediatric TBI trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites.

Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury--Results From an Automated Data Collection System Time-Synched to Drug Administration.

OBJECTIVES: To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury. Currently, data supporting the efficacy of these medications are insufficient. DESIGN: In this prospective observational study, intracranial hypertension (intracranial pressure ≥ 20 mm Hg for > 5 min) was treated by clinical protocol. Administration times of medications for intracranial hypertension (fentanyl, 3% hypertonic saline, mannitol, and pentobarbital) were prospectively recorded and synchronized with an automated database that collected intracranial pressure and cerebral perfusion pressure every 5 seconds. Intracranial pressure crises confounded by external stimulation or mechanical ventilator adjustments were excluded. Mean intracranial pressure and cerebral perfusion pressure from epochs following drug administration were compared with baseline values using Kruskal-Wallis analysis of variance and Dunn test. Frailty modeling was used to analyze the time to intracranial pressure crisis resolution. Mixed-effect models compared intracranial pressure and cerebral perfusion pressure 5 minutes after the medication versus baseline and rates of treatment failure. SETTING: A tertiary care children's hospital. PATIENTS: Children with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 196 doses of fentanyl, hypertonic saline, mannitol, and pentobarbital administered to 16 children (median: 12 doses per patient). Overall, intracranial pressure significantly decreased following the administration of fentanyl, hypertonic saline, and pentobarbital. After controlling for administration of multiple medications, intracranial pressure was decreased following hypertonic saline and pentobarbital administration; cerebral perfusion pressure was decreased following fentanyl and was increased following hypertonic saline administration. After adjusting for significant covariates (including age, Glasgow Coma Scale score, and intracranial pressure), hypertonic saline was associated with a two-fold faster resolution of intracranial hypertension than either fentanyl or pentobarbital. Fentanyl was significantly associated with the most frequent treatment failure. CONCLUSIONS: Intracranial pressure decreased after multiple drug administrations, but hypertonic saline may warrant consideration as the first-line drug for treating intracranial hypertension, as it was associated with the most favorable cerebral hemodynamics and fastest resolution of intracranial hypertension.