Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

The Utilization of Critical Care Resources in Pediatric Neurocritical Care Patients.

OBJECTIVES: To define the prevalence of neurologic diagnoses and evaluate the utilization of critical care and neurocritical care (NCC) resources among children admitted to the PICU. DESIGN: Retrospective cohort analysis. SETTING: Data submitted to the Virtual Pediatric Systems (VPS) database. PATIENTS: All children entered in VPS during 2016 (January 1, 2016, to December 31, 2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 128,688 patients entered into VPS and were comprised of 24.3% NCC admissions and 75.7% general PICU admissions. The NCC cohort was older, represented more scheduled admissions, and was more frequently admitted from the operating room. The NCC cohort also experienced a greater decline in prehospitalization to posthospitalization functional status and required more frequent use of endotracheal intubation, arterial lines, and foley catheters but had an overall shorter duration of PICU and hospital length of stay with a higher mortality rate. One thousand seven hundred fifteen patients at 12 participating institutions were entered into a novel, pilot NCC module evaluating sources of secondary neurologic injury. Four hundred forty-eight patients were manually excluded by the data entrant, leaving 1,267 patients in the module. Of the patients in the module, 75.8% of patients had a NCC diagnosis as their primary diagnosis; they experienced a high prevalence of pathophysiologic events associated with secondary neurologic insult (ranging from hyperglycemia at 10.5% to hyperthermia at 36.8%). CONCLUSIONS: In children admitted to a VPS-contributing PICU, a diagnosis of acute neurologic disease was associated with greater use of resources. We have identified the most common etiologies of acute neurologic disease in the 2016 VPS cohort, and such admissions were associated with significant decrease in functional status, as well as an increase in mortality.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Predictors of intracranial hypertension in children undergoing ICP monitoring after severe traumatic brain injury.

PURPOSE: Intracranial hypertension (ICH) is a common and treatable complication after severe traumatic brain injury (sTBI) in children. Describing the incidence and risk factors for developing ICH after sTBI could impact clinical practice. METHODS: Retrospective cohort study from 2006 to 2015 at two university-affiliated level I pediatric trauma centers of children admitted with accidental or abusive TBI, a post-resuscitation Glasgow Coma Score (GCS) of 8 or less, and an invasive intracranial pressure (ICP) monitor. Bivariate and multivariable logistic regression analysis were performed to identify demographic, injury, and imaging characteristics in patients who received ICP directed therapies for ICH (ICP > 20 mmHg). RESULTS: Eight to 5% (271/321) of monitored patients received ICP directed therapy for ICH during their PICU stay. Ninety-seven percent of patients had an abnormality on CT scan by either the Marshall or the Rotterdam score. Of the analyzed clinical and radiologic variables, only presence of hypoxia prior to PICU arrival, female sex, and a higher Injury Severity Score (ISS) were associated with increased risk of ICH (p < 0.05). CONCLUSIONS: In this retrospective study of clinical practice of ICP monitoring in children after sTBI, the vast majority of children had an abnormal CT scan and experienced ICH requiring clinical intervention. Commonly measured clinical variables and radiologic classification scores did not significantly add to the prediction for developing of ICH and further efforts are needed to define low-risk populations that would not develop ICH.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

The cost of a pediatric neurocritical care program for traumatic brain injury: a retrospective cohort study.

BACKGROUND: Inpatient care for children with severe traumatic brain injury (sTBI) is expensive, with inpatient charges averaging over $70,000 per case (Hospital Inpatient, Children Only, National Statistics. Diagnoses- clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [ https://hcupnet.ahrq.gov/#setup ]). This ranks sTBI in the top quartile of pediatric conditions with the greatest inpatient costs (Hospital Inpatient, Children Only, National Statistics. Diagnoses- clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [ https://hcupnet.ahrq.gov/#setup ]). The Brain Trauma Foundation developed sTBI intensive care guidelines in 2003, with revisions in 2012 (Kochanek, Carney, et. al. PCCM 3:S1-S2, 2012). These guidelines have been widely disseminated, and are associated with improved health outcomes (Pineda, Leonard. et. al. LN 12:45-52, 2013), yet research on the cost of associated hospital care is limited. The objective of this study was to assess the costs of providing hospital care to sTBI patients through a guideline-based Pediatric Neurocritical Care Program (PNCP) implemented at St. Louis Children's Hospital, a pediatric academic medical center in the Midwest United States. METHODS: This is a retrospective cohort study. We used multi-level regression to estimate pre-/post-implementation effects of the PNCP program on inflation adjusted total cost of in-hospital sTBI care. The study population included 58 pediatric patient discharges in the pre-PNCP implementation group (July 15, 1999 - September 17, 2005), and 59 post-implementation patient discharges (September 18, 2005 - January 15, 2012). RESULTS: Implementation of the PNCP was associated with a non-significant difference in the cost of care between the pre- and post-implementation periods (eß = 1.028, p = 0.687). CONCLUSIONS: Implementation of the PNCP to support delivery of guideline-based care for children with sTBI did not change the total per-patient cost of in-hospital care. A key strength of this study was its use of hospital cost data rather than charges. Future research should consider the longitudinal post-hospitalization costs of this approach to sTBI care.

Implementation strategies in pediatric neurocritical care.

PURPOSE OF REVIEW: Brain-directed critical care for children is a relatively new area of subspecialization in pediatric critical care. Pediatric neurocritical care teams combine the expertise of neurology, neurosurgery, and critical care medicine. The positive impact of delivering specialized care to pediatric patients with acute neurological illness is becoming more apparent, but the optimum way to implement and sustain the delivery of this is complicated and poorly understood. We aim to provide emerging evidence supporting that effective implementation of pediatric neurocritical care pathways can improve patient survival and outcomes. We also provide an overview of the most effective strategies across the field of implementation science that can facilitate deployment of neurocritical care pathways in the pediatric ICU. RECENT FINDINGS: Implementation strategies can broadly be grouped according to six categories: planning, educating, restructuring, financing, managing quality, and attending to the policy context. Using a combination of these strategies in the last decade, several institutions have improved patient morbidity and mortality. Although much work remains to be done, emerging evidence supports that implementation of evidence-based care pathways for critically ill children with two common neurological diagnoses - status epilepticus and traumatic brain injury - improves outcomes. SUMMARY: Pediatric and neonatal neurocritical care programs that support evidence-based care can be effectively structured using appropriately sequenced implementation strategies to improve outcomes across a variety of patient populations and in a variety of healthcare settings.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

OBJECTIVES: Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. DESIGN: Retrospective analysis of a public access dataset. SETTING: Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. PATIENTS: Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. CONCLUSIONS: This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Brain metabolism and severe pediatric traumatic brain injury.

Age-dependent changes in brain metabolism may influence the response to and tolerance of secondary insults, potentially affecting outcomes. More complete characterization of brain metabolism across the clinical trajectory of severe pediatric TBI is needed to improve our ability to measure and better mitigate the impact of secondary insults. Better management of secondary insults will impact clinical care and the probability of success of future neuroprotective clinical trials. Improved bedside monitoring and imaging technologies will be required to achieve these goals. Effective and sustained integration of brain metabolism information into the pediatric critical care setting will be equally challenging and important.

Emergency Neurological Life Support: Acute Non-traumatic Weakness.

Acute non-traumatic weakness may be life-threatening if it involves the respiratory muscles and/or is associated with autonomic dysfunction. Most patients presenting with acute muscle weakness have a worsening neurological disorder that requires a rapid, systematic evaluation and detailed neurological exam to localize the disorder. Urgent laboratory tests and neuroimaging are needed to confirm the diagnosis. Because acute weakness is a common presenting sign of neurological emergencies, it was chosen as an Emergency Neurological Life Support protocol. Causes of acute non-traumatic weakness are discussed here by both presenting clinical signs and anatomical location. For each diagnosis, key features of the history, examination, investigations, and treatment are outlined in the included tables or in the "Appendix".

Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.

OBJECTIVE: To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: PICU in a university-affiliated children's hospital level I trauma center. PATIENTS: Thirty-one children 0-18 years of age with severe traumatic brain injury (Glasgow Coma Scale score of ≤ 8) who received bolus doses of fentanyl and/or midazolam for treatment of episodic intracranial hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial hypertension exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial hypertension) was calculated in 15-minute epochs before and after administration of fentanyl and/or midazolam for the treatment of episodic intracranial hypertension. Our primary outcome measure, the difference between predrug and postdrug administration epochs (Δarea under the curve-intracranial hypertension), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with Δarea under the curve-intracranial hypertension. In a mixed-effects model, with patient as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial hypertension increased after administration of fentanyl and/or midazolam (overall aggregate mean Δarea under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean Δarea under the curve-intracranial hypertension increased significantly after administration of high-dose fentanyl (p = 0.02), low-dose midazolam (p = 0.006), and high-dose fentanyl plus low-dose midazolam (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean Δarea under the curve-cerebral perfusion pressure). CONCLUSIONS: Bolus dosing of fentanyl and midazolam fails to reduce the intracranial hypertension burden when administered for episodic intracranial hypertension. Paradoxically, we observed an overall increase in intracranial hypertension burden following drug administration, even after accounting for within-subject effects and time after injury. Future work is needed to confirm these findings in a prospective study design.

Emergency Neurological Life Support: Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subset of stroke due to bleeding within the parenchyma of the brain. It is potentially lethal, and survival depends on ensuring an adequate airway, reversal of coagulopathy, and proper diagnosis. ICH was chosen as an Emergency Neurological Life Support protocol because intervention within the first critical hour may improve outcome, and it is critical to have site-specific protocols to drive care quickly and efficiently.

Emergency Neurological Life Support: Traumatic Spine Injury.

Traumatic spine injuries (TSIs) carry significantly high risks of morbidity, mortality, and exorbitant health care costs from associated medical needs following injury. For these reasons, TSI was chosen as an ENLS protocol. This article offers a comprehensive review on the management of spinal column injuries using the best available evidence. Alhough the review focuses primarily on cervical spinal column injuries, thoracolumbar injuries are briefly discussed as well. The initial emergency department clinical evaluation of possible spinal fractures and cord injuries, along with the definitive early management of confirmed injuries, is also covered.

A Survey of Pediatric Neurocritical Care Fellowship Training in North America.

BACKGROUND: Pediatric neurocritical care (PNCC) has emerged as a field to care for children at the intersection of critical illness and neurological dysfunction. PNCC fellowship programs evolved over the past decade to train physicians to fill this clinical need. We aimed to characterize PNCC fellowship training infrastructure and curriculum in the United States and Canada. METHODS: Web-based survey of PNCC fellowship program leaders during November 2019 to January 2020. RESULTS: There were 14 self-identified PNCC fellowship programs. The programs were supported by Child Neurology and/or Pediatric Critical Care Medicine divisions at tertiary/quaternary care institutions. Most programs accepted trainees who were board-eligible or board-certified in child neurology or pediatric critical care medicine. Clinical training consisted mostly of rotations providing PNCC consultation (n = 13) or as a provider on the pediatric intensive care unit-based neurointensive care team (n = 2). PNCC-specific didactics were delivered at most institutions (n = 13). All institutions provided training in electroencephalography use in the intensive care unit and declaration of death by neurological criteria (n = 14). Scholarly activity was supported by most programs, including protected time for research (n = 10). CONCLUSIONS: We characterized PNCC fellowship training in the United States and Canada, which in this continuously evolving field, lays the foundation for exploring standardization of training going forward.

Depression of whole-brain oxygen extraction fraction is associated with poor outcome in pediatric traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Metabolic failure is an integral component of the pathological aftermath of TBI. The oxygen extraction fraction (OEF) is a valuable parameter for characterization and description of metabolic abnormalities; however, OEF measurement has required either invasive procedures or the use of ionizing radiation, which significantly limits its use in pediatric research. RESULTS: Patients with TBI had depressed OEF levels that correlated with the severity of injury. In addition, the OEF measured within 2 weeks of injury was predictive of patient outcome at 3 mo after injury. In pediatric TBI patients, low OEF-a marker of metabolic dysfunction-correlates with the severity of injury and outcome. DISCUSSION: Our findings support previous literature on the role of metabolic dysfunction after TBI. METHODS: Using a recently developed magnetic resonance (MR) technique for the measurement of oxygen saturation, we determined the whole-brain OEF in both pediatric TBI patients and in healthy controls. Injury and outcome were classified using pediatric versions of the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), respectively.

Trends and variation in repeat neuroimaging for children with traumatic intracranial hemorrhage.

OBJECTIVES: We aimed to determine trends and institutional variation in repeat neuroimaging in children with traumatic intracranial hemorrhage and to identify factors associated with neuroimaging modality (subsequent magnetic resonance imaging [MRI] vs computed tomography [CT]). METHODS: We conducted a retrospective cross-sectional study of 35 hospitals in the Pediatric Health Information System database. We included children <18 years of age hospitalized from 2010-2019 with intracranial hemorrhage and who underwent a brain CT. We calculated repeat neuroimaging rates by modality and used regression analyses to examine temporal trends. We used hierarchical logistic regression to identify factors associated with subsequent MRI versus repeat CT, controlling for hospital. RESULTS: We identified 12,714 children with intracranial hemorrhage, of which 5072 with repeat neuroimaging were studied. Of the 5072 children with repeat neuroimaging, repeat CT was performed in 67.6% (n = 3429) and subsequent MRI in 32.4% (n = 1643). Overall repeat neuroimaging with either a CT or MRI remained similar from 2010-2019 (P = 0.431); however, repeat CT scans significantly decreased (P = 0.001); whereas, MRIs significantly increased (P < 0.001). Repeat neuroimaging by hospital ranged from 20%-80%. After controlling for institution, subsequent MRI was more likely to be used in younger children and children who did not receive hyperosmotic agents, neurosurgical interventions, or intensive care unit admission (all P-values <0.001). CONCLUSIONS: We found that repeat neuroimaging rates for children with intracranial hemorrhage vary substantially by institution. We also found that although MRI was increasingly used to re-image these children, overall repeat neuroimaging rates (CT or MRI) have not decreased over the past decade. Future work to implement optimal utilization of neuroimaging in these children is needed.

Changes in Pediatric ICU Utilization and Clinical Trends During the Coronavirus Pandemic.

BACKGROUND: Children have been less affected by the COVID-19 pandemic, but its repercussions on pediatric illnesses may have been significant. This study examines the indirect impact of the pandemic on a population of critically ill children in the United States. RESEARCH QUESTION: Were there significantly fewer critically ill children admitted to PICUs during the second quarter of 2020, and were there significant changes in the types of diseases admitted? STUDY DESIGN AND METHODS: This retrospective observational cohort study used the Virtual Pediatric Systems database. Participants were 160,295 children admitted to the PICU at 77 sites in the United States during quarters 1 (Q1) and 2 (Q2) of 2017 to 2019 (pre-COVID-19) and 2020 (COVID-19). RESULTS: The average number of admissions was similar between pre-COVID-19 Q1 and COVID-19 Q1 but decreased by 32% from pre-COVID-19 Q2 to COVID-19 Q2 (20,157 to 13,627 admissions per quarter). The largest decreases were in respiratory conditions, including asthma (1,327 subjects in pre-COVID-19 Q2 (6.6% of patients) vs 241 subjects in COVID-19 Q2 (1.8%; P < .001) and bronchiolitis (1,299 [6.5%] vs 121 [0.9%]; P < .001). The percentage of trauma admissions increased, although the raw number of trauma admissions decreased. Admissions for diabetes mellitus and poisoning/ingestion also increased. In the multivariable model, illness severity-adjusted odds of ICU mortality for PICU patients during COVID-19 Q2 increased compared with pre-COVID-19 Q2 (OR, 1.165; 95% CI, 1.00-1.357; P = .049). INTERPRETATION: Pediatric critical illness admissions decreased substantially during the second quarter of 2020, with significant changes in the types of diseases seen in PICUs in the United States. There was an increase in mortality in children admitted to the PICU during this period.

Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury.

OBJECTIVE: Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP 9.3), is highly abundant in neurons. To assess the reliability of UCH-L1 as a potential biomarker for traumatic brain injury (TBI) this study compared cerebrospinal fluid (CSF) levels of UCH-L1 from adult patients with severe TBI to uninjured controls; and examined the relationship between levels with severity of injury, complications and functional outcome. DESIGN: This study was designed as prospective case control study. PATIENTS: This study enrolled 66 patients, 41 with severe TBI, defined by a Glasgow coma scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring and 25 controls without TBI requiring CSF drainage for other medical reasons. SETTING: : Two hospital system level I trauma centers. MEASUREMENTS AND MAIN RESULTS: Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hrs following TBI and analyzed for UCH-L1. Injury severity was assessed by the GCS score, Marshall Classification on computed tomography and a complicated postinjury course. Mortality was assessed at 6 wks and long-term outcome was assessed using the Glasgow outcome score 6 months after injury. TBI patients had significantly elevated CSF levels of UCH-L1 at each time point after injury compared to uninjured controls. Overall mean levels of UCH-L1 in TBI patients was 44.2 ng/mL (+/-7.9) compared with 2.7 ng/mL (+/-0.7) in controls (p <.001). There were significantly higher levels of UCH-L1 in patients with a lower GCS score at 24 hrs, in those with postinjury complications, in those with 6-wk mortality, and in those with a poor 6-month dichotomized Glasgow outcome score. CONCLUSIONS: These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.