Severe Pediatric Traumatic Brain Injury Research Articles

Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" Dataset, 2014-2017.

To compare levetiracetam and phenytoin as prophylaxis for the short-term development of status epilepticus (SE) during care of pediatric patients with acute severe traumatic brain injury (TBI). Nonprespecified secondary analysis using propensity score matching. We used the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT NCT04077411) dataset (2014-2017). Patients less than 18 years old with Glasgow Coma Scale Score less than or equal to 8 who received levetiracetam or phenytoin as a prophylactic anticonvulsant therapy. None. Of the 516 total patients who qualified for the case-control study, 372 (72.1%) patients received levetiracetam, and 144 (27.9%) received phenytoin. After propensity score matching, the pair-matched analysis with 133 in each group failed to identify an association between levetiracetam versus phenytoin use and occurrent of SE (3.8% vs. 0.8%, p = 0.22), or mortality (i.e., in-hospital, 30-d and 60-d). However, on closer inspection of the statistical testing, we cannot exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with the following: up to a mean difference of 7.3% greater prevalence of SE; up to a mean difference of 13.9%, 12.1%, and 13.9% greater mortality during the hospital stay, and 30-, and 60-days after hospital arrival, respectively. Last, analysis of 6 months Glasgow Outcome Scale Extended score in those without premorbid comorbidities, there was an association between favorable outcomes and use of phenytoin rather than levetiracetam prophylaxis. In ADAPT, the decision to use prophylactic levetiracetam versus phenytoin failed to show an association with occurrence of subsequent SE, or mortality. However, we are unable to exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with greater prevalence of SE and mortality. We are unable to make any recommendation about one prophylactic anticonvulsant medication over the other, but recommend that further larger, contemporary studies in severe pediatric TBI are carried out.

Elucidating a genomic signature associated with behavioral and executive function after moderate to severe pediatric TBI: a systems biology informed approach

Introduction: There is significant unexplained variability in behavioral and executive functioning after pediatric traumatic brain injury (TBI). Prior research indicates that there are likely genetic contributions; however, current research is limited. The purpose of this study is to use a systems biology informed approach to characterize the genomic signature related to behavioral and executive functioning ∼12 months after moderate through severe TBI in children.Methods: Participants were from two prospective cohorts of children with severe TBI (Cohort #1) and moderate-severe TBI and an orthopedic injury (OI) group (Cohort #2). Participants included 196 children (n = 72 and n = 124 total from each respective cohort), ranging in age between 0–17 years at the time of injury. In total, 86 children had severe TBI, 49 had moderate TBI, and 61 had an OI. Global behavioral functioning assessed via the Child Behavior Checklist and executive function assessed via the Behavioral Rating Inventory of Executive Function at ∼ 12 months post injury served as outcomes. To test for a genomic signature, we compared the number of nominally significant (p < 0.05) polymorphisms associated with the outcomes in our systems biology identified genes to a set 10,000 permutations using control genes (e.g., not implicated by systems biology). We used the ToppFun application from Toppgene Suite to identify enriched biologic processes likely to be associated with behavioral and executive function outcomes.Results: At 12 months post injury, injury type (TBI vs OI) by polymorphism interaction was significantly enriched in systems biology selected genes for behavioral and executive function outcomes, suggesting these genes form a genomic signature. Effect sizes of the associations from our genes of interest ranged from .2–.5 for the top 5% of variants. Systems biology analysis of the variants associated with the top 5% effect sizes indicated enrichment in several specific biologic processes and systems.Discussion: Findings indicate that a genomic signature may explain heterogeneity of behavioral and executive outcomes after moderate and severe TBI. This work provides the foundation for constructing genomic signatures and integrating systems biology and genetic information into future recovery, prognostic, and treatment algorithms.

Behavior problems 7 years after severe childhood traumatic brain injury: Results of the Traumatisme Grave de L'Enfant study.

To investigate the occurrence of behavioral problems 7 years after severe pediatric traumatic brain injury (TBI), and their evolution from 3 months to 7 years postinjury. Thirty-four participants, 38% girls, M (SD) age at injury 7.6 (4.7) years, age at assessment 15 (4.6) years, underwent comprehensive assessments 7 years after severe TBI from March 2014 to March 2016 and were matched to a control group by age, gender, and parental education. A subgroup of 20 participants had available behavioral assessments at 3, 12, and 24 months postinjury. Internalizing, externalizing, and total behavioral problems were assessed with self- and parent reports of the Achenbach's Behavioral Checklist. Additional data included sociodemographic background, initial injury severity, and specific outcomes assessed concurrently 7 years postinjury. Compared to controls: (a) a significant proportion of participants with severe TBI fell above the clinical cutoff for self- (42%) and parent-reported (36%) externalizing problems, but not for self- (33%) or parent-reported (45%) internalizing problems; (b) withdrawn/depressed, intrusive behavior, and somatic complaints were significantly higher in self-reports; and (c) rule-breaking behavior, attention, and social problems were significantly higher in parent reports. Parent-reported internalizing problems were associated with older age at injury, whereas externalizing problems correlated with greater injury severity and concurrent levels of greater overall disability, lower intellectual ability, and poorer family functioning. In multiple hierarchical regression analyses, overall disability and worse family functioning significantly predicted externalizing problems. Parent-reported internalizing and externalizing problems persisted over time. These results highlight the importance of long-term follow-up and individualized behavioral interventions for children who sustained severe TBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Letter: Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Study Protocol.

Letter: Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Study Protocol.

In Reply: Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Study Protocol.

In Reply: Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Study Protocol.

Accuracy of Early Neuroprognostication in Pediatric Severe Traumatic Brain Injury

BackgroundChildren with severe traumatic brain injury (sTBI) are at risk for neurological sequelae impacting function. Clinicians are tasked with neuroprognostication to assist in decision-making. We describe a single-center study assessing clinicians’ neuroprognostication accuracy. MethodsClinicians of various specialties caring for children with sTBI were asked to predict their patients' functioning three to six months postinjury. Clinicians were asked to participate in the study if their patient had survived but not returned to baseline between day 4 and 7 postinjury. The outcome tool utilized was the functional status scale (FSS), ranging from 6 to 30 (best-worst function). Predicted scores were compared with actual scores three to six months postinjury. Lin concordance correlation coefficients were used to estimate agreement between predicted and actual FSS. Outcome was dichotomized as good (FSS 6 to 8) or poor (FSS ≥9). Positive and negative predictive values for poor outcome were calculated. Pessimistic prognostic prediction was defined as predicted worse outcome by ≥3 FSS points. Demographic and clinical variables were collected. ResultsA total of 107 surveys were collected on 24 patients. Two children died. Fifteen children had complete (FSS = 6) or near-complete (FSS = 7) recovery. Mean predicted and actual FSS scores were 10.8 (S.D. 5.6) and 8.6 (S.D. 4.1), respectively. Predicted FSS scores were higher than actual scores (P < 0.001). Eight children had collective pessimistic prognostic prediction. ConclusionsClinicians predicted worse functional outcomes, despite high percentage of patients with near-normal function at follow-up clinic. Certain patient and provider factors were noted to impact accuracy and need to be studied in larger cohorts.

The neurological wake-up test in severe pediatric traumatic brain injury: a long term, single-center experience.

To describe the use and outcomes of the neurological wake-up test (NWT) in pediatric severe traumatic brain injury (pTBI). Retrospective single-center observational cohort study. Medical-surgical tertiary pediatric intensive care unit (PICU) in a university medical center and Level 1 Trauma Center. Children younger than 18 years with severe TBI [i.e., Glasgow Coma Scale (GCS) of ≤8] admitted between January 2010 and December 2020. Subjects with non-traumatic brain injury were excluded. Of 168 TBI patients admitted, 36 (21%) met the inclusion criteria. Median age was 8.5 years [2 months to 16 years], 5 patients were younger than 6 months. Median initial Glasgow Coma Scale (GCS) and Glasgow Motor Scale (GMS) was 6 [3-8] and 3 [1-5]. NWTs were initiated in 14 (39%) patients, with 7 (50%) labelled as successful. Fall from a height was the underlying injury mechanism in those seven. NWT-failure occurred in patients admitted after traffic accidents. Sedation use in both NWT-subgroups (successful vs. failure) was comparable. Cause of NWT-failure was non-arousal (71%) or severe agitation (29%). Subjects with NWT failure subsequently had radiological examination (29%), repeat NWT (43%), continuous interruption of sedation (14%) or intracranial pressure (ICP) monitoring (14%). The primary reason for not doing NWTs was intracranial hypertension in 59%. Compared to the NWT-group, the non-NWT group had a higher PRISM III score (18.9 vs. 10.6), lower GCS/GMS at discharge, more associated trauma, and circulatory support. Nine patients (25%) died during their PICU admission, none of them had an NWT. We observed limited use of NWTs in pediatric severe TBI. Patients who failed the NWT were indistinguishable from those without NWT. Both groups were more severely affected compared to the NWT successes. Therefore, our results may indicate that only a select group of severe pTBI patients qualify for the NWT.

Long-term burden of informal caregiver 7-years after severe childhood traumatic brain injury in the traumatisme grave de l’Enfant (TGE) study

ABSTRACT Objective To investigate reported burden by the Primary Family Caregiver (PFC) 7-years after severe pediatric traumatic brain injury in the TGE (Traumatisme Grave de l’Enfant) longitudinal study. Methods Subjective burden was estimated with the Zarit Burden Inventory (ZBI) in 36 PFC (parents), who rated their own health status (Medical Outcome Study Short Form-12), family functioning and their child’s level of care and needs (Pediatric/Adult Care And Needs Scale [PCANS/CANS]). Data collection included: child and PFC sociodemographic characteristics, injury-related factors, ‘objective’ (e.g. overall level of disability: Glasgow Outcome Scale – Extended, GOS-E/GOS-E-Peds) and ‘subjective’ outcomes (e.g. participation, behavior, executive functions, quality of life and fatigue). Results 25% of PFC reported mild-moderate burden, and 19% moderate-severe burden. Higher burden correlated with worse outcomes in all ‘subjective’ PFC-rated outcomes, and with self-reported participation. The ZBI correlated strongly with CANS/PCANS and GOS-E/GOS-E-Peds. Overall level of disability and PFC-reported executive functioning explained 62% of the ZBI variance. For equal levels of disability, burden was higher when PFC reported a ‘negative’ picture of their child. Conclusion Significant PFC-reported burden 7-years post-injury was associated with overall disability and ‘subjective’ PFC-rated outcomes. Factors influencing parental burden in the long term should be identified and psychological support implemented over time.

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

BackgroundSevere 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. MethodsWe 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. ResultsAmong 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). ConclusionsExtracranial 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.

Outcomes of Repeat Surgery in Pediatric Severe Traumatic Brain Injury: An Analysis from Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial

BackgroundEarly operative intervention, craniotomy (CO), and/or craniectomy (DC) are occasionally warranted in severe traumatic brain injury (TBI). Persistent increased intracranial pressure (ICP) or accumulation of intracranial hematoma post-surgery can result in higher mortality and morbidity. There is a gap in information regarding the outcome of repeat surgery (RS) in pediatric patients with severe TBI. MethodsAn observational cohort study titled Approaches and Decisions in Acute Pediatric Trial (ADAPT) of severe TBI data was obtained from the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System. All pediatric patients who underwent CO or DC, survived more than 44 hours and were found to have persistent elevated ICP >20 for two consecutive hours were included in the study. The purpose of the study was to find the outcomes of RS in pediatric severe TBI. Propensity based matching was used to find the outcomes. The primary outcome was 60-day mortality. ResultsOut of 1000 total patients enrolled in the ADAPT trial, 160 patients qualified for this study. Propensity score matching created 13 pairs of patients. There were no significant differences found between the groups who had RS vs. those who did not have repeat surgery (NRS). There were no significant differences found between the groups regarding 60-day mortality, median hospital days, median ICU days, and 6-month favorable outcome on Glasgow Outcome Scale Extended (GOS-E) score. ConclusionThere was no difference in mortality between patients who underwent a second surgery and patients who did not have to undergo a second surgery.

Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Research Algorithms.

The efficacy of our current approach to incorporating intracranial pressure (ICP) data into pediatric severe traumatic brain injury (sTBI) management is incompletely understood, lacking data from multicenter, prospective, randomized studies. The National Institutes of Health-supported Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial will compare outcomes from pediatric sTBI of a management protocol based on ICP monitoring vs 1 based on imaging and clinical examination without monitoring. Because no applicable comprehensive management algorithms for either cohort are available, it was necessary to develop them. A consensus conference involving the 21 intensivists and neurosurgeons from the 8 trial sites used Delphi-based methodology to formulate management algorithms for both study cohorts. We included recommendations from the latest Brain Trauma Foundation pediatric sTBI guidelines and the consensus-based adult algorithms (Seattle International Brain Injury Consensus Conference/Consensus Revised Imaging and Clinical Examination) wherever relevant. We used a consensus threshold of 80%. We developed comprehensive management algorithms for monitored and nonmonitored cohort children with sTBI. We defined suspected intracranial hypertension for the nonmonitored group, set minimum number and timing of computed tomography scans, specified minimal age-adjusted mean arterial pressure and cerebral perfusion pressure targets, defined clinical neuroworsening, described minimal requisites for intensive care unit management, produced tiered management algorithms for both groups, and listed treatments not routinely used. We will study these protocols in the Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial in low- and middle-income countries. Second, we present them here for consideration as prototype pediatric sTBI management algorithms in the absence of published alternatives, acknowledging their limited evidentiary status. Therefore, herein, we describe our study design only, not recommended treatment protocols.

Relationship of pre-hospital clinical status with behavior of intracranial pressure and outcomes in pediatric patients with severe head trauma.

Introduction: The prehospital phase of the management of pediatric severe traumatic brain injury may have a direct influence on the results. Objective: To evaluate the influence of prehospital variables on intracranial pressure and the results in pediatric patients with severe TBI. Method: A descriptive study of 41 pediatric patients who were admitted to the medical emergency department and later admitted to the pediatric intensive care unit due to severe head trauma was carried out between January 2003 and December 2018. Results: children aged 5-17 years predominate, and the highest number of cases were received between 0-3h at the neurotrauma center. Of the 41 cases, 27 arrived with a non-expedited airway and hypoxia was verified upon arrival by pulse oximetry. A correlation was observed between arterial hypotension on admission and elevated intracranial pressure in 9 of 15 children (60%) and in the deceased (40%). Discussion: Clinical conditions, oxygenation, arterial hypotension, and treatment in the prehospital phase may influence the state of intracranial pressure and other intracranial variables in pediatric patients with severe head injury.

Pediatric Moderate and Severe Traumatic Brain Injury: A Systematic Review of Clinical Practice Guideline Recommendations.

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE®, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.

Measuring Energy Requirements of Traumatic Brain Injury Patients in Pediatric Intensive Care With Indirect Calorimetry: A Comparison With Empiric Methods.

Energy requirements following moderate or severe pediatric traumatic brain injury (TBI) have not been fully elucidated. Indirect calorimetry (IC) is the gold standard for measuring resting energy expenditure (MREE) in PICU. However, technical complexity limits its use. We aimed to determine whether MREE differs from standard of care energy estimation and delivery in a cohort of pediatric patients following moderate to severe TBI during PICU admission. Retrospective case series study. Single-center, 16-bed general PICU in Canada between May 2011 and January 2019. Children (0-18 yr) admitted to a PICU for moderate (Glasgow Coma Scale [GCS] 9-12) to severe TBI (GCS < 9) and had an IC study performed while mechanically ventilated. None. During the study period, 245 patients were admitted with the diagnosis of trauma with TBI. The study includes a convenience sample of 26 patients with severe ( n = 23) and moderate ( n = 3) TBI who underwent a total of 34 IC measurements. MREE varied considerably from 29% to 144% of predicted energy expenditure. Using Bland-Altman comparative analysis, neither Schofield nor World Health Organization predictive equations were in agreement with MREE. Only one measurement revealed that the patient was appropriately fed (energy provided in nutrition support was within 10% of MREE); 10 (38%) measurements revealed overfeeding and 15 (58%) underfeeding at the time of testing. The present study adds to the small body of literature highlighting the limitations of predictive equations to evaluate energy requirements following moderate to severe pediatric TBI. IC, when feasible, should be used as the preferred method to orient PICU teams to feed such vulnerable patients.

Optic nerve sheath diameter and pulsatility index for the diagnosis and follow-up in pediatric traumatic brain injury: a prospective observational cohort study.

Invasive neuromonitoring could be difficult in children with traumatic brain injury (TBI). This study aimed to determine whether noninvasive intracranial pressure (nICP), calculated via pulsatility index (PI) and optic nerve sheath diameter (ONSD) had correlated with each other and patient outcome. All moderate-severe TBI patients were eligible. Patients with a diagnosis of intoxication that did not affect the mental status or cardiovascular system were enrolled as controls. The PI measurements were routinely performed bilaterally on the middle cerebral artery. A software (QLAB's Q-Apps) was used to calculate PI, which further placed the ICP equation of Bellner et al. Linear probe with a 10MHz frequency transducer to measure ONSD, which further placed the ICP equation of Robba et al. All measurements were performed by a point-of-care ultrasound certified pediatric intensivist under the supervision of a neurocritical care specialist, before and 30min after a hypertonic saline (HTS) infusion for every 6h when the patient's mean arterial pressure, heart rate, body temperature, hemoglobin, and blood CO2 levels were within normal ranges. The secondary outcome was the effect of hypertonic saline (HTS) on nICP. Delta-sodium values of each HTS infusion were calculated as a difference between pre- and post-measurements. Twenty-five TBI patients (200 measurements) and 19 controls (57 measurements) were included. Median nICP-PI and nICP-ONSD on admission were significantly higher in the TBI group (11.03 (9.98-12.63), p = 0.004, and 13.14 (12.27-14.64), p < 0.001, respectively). Median nICP-ONSD of severe TBI patients were higher than moderate TBI patients (13.58 (13.14-15.71) and 12.30 (9.83-13.14), respectively, p = 0.013). The median nICP-PI was the same across the type of injury (falls and motor vehicle accidents), while the median nICP-ONSD of the motor vehicle accident group was higher than falls. The first nICP-PI and nICP-ONSD measurements in PICU and admission pGCS were negatively correlated (r =  - 0.562, p = 0.003 and r =  - 0.582, p = 0.002, respectively). The mean nICP-ONSD during the study period and admission pGCS and GOS-E peds score significantly correlated. However, the Bland-Altman plots showed significant bias between the two methods of ICP except after 5th dose of HTS. All nICP values significantly decreased in time, and it was most obvious after the 5th dose of HTS. No significant correlations were found between delta sodium levels and nICP. Noninvasive estimation of ICP is helpful for the management of pediatric severe TBI patients. nICP driven by ONSD is more consistent with clinical findings of increased ICP but not useful as a follow-up tool in acute management because of slow circulation of CSF around the optic sheath. The correlation between admission GCS scores and GOS-E peds score favors ONSD as a good candidate for determining disease severity and predicting long-term outcomes.

Early metabolic derangements and unfavorable outcomes in pediatric traumatic brain injury: a retrospective multi-center cohort study.

To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU). Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h). Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died. We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

Barbiturate coma treatment in children with refractory intracranial hypertension due to traumatic brain injury; is it useful?

In pediatric severe Traumatic Brain Injury (TBI) the appearance of refractory intracranial hypertension is related to an unfavourable prognosis. Severe TBI (ECG &lt;8) is present in 60% of polytrauma children and is associated with high morbidity and mortality. The monitoring of intracranial pressure (ICP) and the treatment of intracranial hypertension have been subjects of attention in neurotrauma for years in the evidence-based guidelines currently being a topic of discussion. Currently the guides based on evidenceshowing acceptance of some guidelines for the management of intracranial hypertension, within the most accepted of sedatives/analgesics, hyperosmolar agents (hypertonic saline solution HTS and mannitol) and barbiturates, although the level of evidence of these recommendations is insufficient to standardize such management in the centers of attention.

Low Morbidity and Mortality in Children with Severe Traumatic Brain Injury Treated According to the Lund Concept: A Population-Based Study.

Previous reports of mortality and morbidity in pediatric severe traumatic brain injury (TBI) vary considerably, with few population-based studies. Mortality rates from 3-33 % and varying morbidity have been reported, most commonly using the Extended Glasgow Outcome Scale (eGOS). The Lund concept is a treatment algorithm for severe TBI aiming at controlling intracranial pressure (ICP) by reducing cerebral perfusion pressure (CPP). The aim of the present study was to retrospectively assess mortality and morbidity in a population of pediatric TBI treated according to the Lund concept. All cases of severe pediatric TBI (age <18 years) in the southern region of Sweden during 19 years were identified. Patients were treated according to the Lund concept. Mortality, eGOS, ICP, CPP, time in the neurosurgical intensive care unit (NICU), drugs delivered and surgical procedures were recorded. Data were analyzed both by dichotomized outcomes and by ordinal statistics. A total of 135 cases of severe TBI <18 years of age were recorded (incidence 2.0/100000) and 86 patients were admitted to the tertiary NICU. Mortality including all cases was 43% (mortality rate 0.7/100,000) and in NICU 10%. Outcome was good in 60%, moderate in 25%, unfavorable in 15%, with none in a vegetative status. In both dichotomized and ordinal analyses, CPP <40 mm Hg and ICP >15 were associated with poor outcome, supporting current guidelines. However, high CPP also was associated with increased mortality and morbidity, supporting that elevated CPP might increase cerebral edema. In this study, the Lund concept resulted in low mortality and a favorable outcome in a majority of severe pediatric TBI patients; however, randomized controlled trials are warranted to verify this.

Early-Onset Ventilator-Associated Pneumonia in Pediatric Severe Traumatic Brain Injury.

Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI. This is a retrospective cohort study at a quaternary referral children's hospital with a level I trauma center designation. Inclusion criteria were patients aged 0-18years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models. After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6years, P = 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (P = 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive Staphylococcus aureus was the most common isolate grown, followed by Hemophilus influenza, with most VAP occurring on days 2-5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5, P = 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP. Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27-41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI.

Technical feasibility of using auditory phase-targeted stimulation after pediatric severe traumatic brain injury in an intensive care setting

BackgroundSupplementary treatment options after pediatric severe traumatic brain injury (TBI) are needed to improve neurodevelopmental outcome. Evidence suggests enhancement of brain delta waves via auditory phase-targeted stimulation might support neuronal reorganization, however, this method has never been applied in analgosedated patients on the pediatric intensive care unit (PICU). Therefore, we conducted a feasibility study to investigate this approach: In a first recording phase, we examined feasibility of recording over time and in a second stimulation phase, we applied stimulation to address tolerability and efficacy.MethodsPediatric patients (> 12 months of age) with severe TBI were included between May 2019 and August 2021. An electroencephalography (EEG) device capable of automatic delta wave detection and sound delivery through headphones was used to record brain activity and for stimulation (MHSL-SleepBand version 2). Stimulation tolerability was evaluated based on report of nurses, visual inspection of EEG data and clinical signals (heart rate, intracranial pressure), and whether escalation of therapy to reduce intracranial pressure was needed. Stimulation efficacy was investigated by comparing EEG power spectra of active stimulation versus muted stimulation (unpaired t-tests).ResultsIn total, 4 out of 32 TBI patients admitted to the PICU (12.5%) between 4 and 15 years of age were enrolled in the study. All patients were enrolled in the recording phase and the last one also to the stimulation phase. Recordings started within 5 days after insult and lasted for 1–4 days. Overall, 23–88 h of EEG data per patient were collected. In patient 4, stimulation was enabled for 50 min: No signs of patient stress reactions were observed. Power spectrums between active and muted stimulation were not statistically different (all P > .05).ConclusionResults suggests good feasibility of continuously applying devices needed for auditory stimulation over multiple days in pediatric patients with TBI on PICU. Very preliminary evidence suggests good tolerability of auditory stimuli, but efficacy of auditory stimuli to enhance delta waves remains unclear and requires further investigation. However, only low numbers of severe TBI patients could be enrolled in the study and, thus, future studies should consider an international multicentre approach.