Lessons learned after 20 years of real-world experience with natalizumab.

BACKGROUND: While natalizumab (NTZ) is an effective therapy for multiple sclerosis (MS), it is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). After 20 years (2002-2022) of experience with NTZ at our center, we observed no cases of PML. OBJECTIVES: We evaluated the likelihood of experiencing PML in a subset of our treatment cohort, as well as reviewed treatment practices at our center that may mitigate PML risk. METHODS: For this retrospective study, we reviewed patient characteristics, treatment practices, and clinical and MRI findings in patients receiving NTZ from 2006 to 2020. Observation of no PML cases was compared to the global and US PML incidences, and to the expected incidence based on published risk estimates. RESULTS: 766 patients were evaluated. The number of NTZ infusions received ranged from 1 to 126, with a mean of 28. Patients received neurological examination prior to each infusion, which sometimes resulted in a pause in therapy to rule out PML if clinical worsening occurred. Extended interval dosing (EID) was the overall dosing schedule for 31% of patients. EID did not result in higher rates of radiological disease worsening than standard interval dosing (SID) patients. Depending on the analysis conducted, the finding of 0 PML cases in our cohort ranged from slightly unexpected to slightly expected. CONCLUSIONS: The utilization of EID as well as regular clinical monitoring of patients may have lowered PML risk while still maintaining NTZ efficacy.

Pharmacodynamics of natalizumab extended interval dosing in MS.

OBJECTIVE: To determine if the concentration and saturation of natalizumab (NTZ) administration at extended interval dosing (EID; every 5-8 weeks) over 18 months is able to be maintained in the range considered adequate to sustain the clinical efficacy of NTZ. METHODS: In a cross-sectional assessment of patients with multiple sclerosis (MS) who received standard interval dosing (every 4 weeks) or EID, serum NTZ concentrations were measured using ELISA, and α4-integrin receptor saturations were analyzed via cytometry, in blood samples obtained at trough timepoints. RESULTS: Trough serum concentration was above the "therapeutic" concentration of 2.0 µg/mL in 72% of EID patients. Trough saturation was above the "therapeutic" 50% threshold in 79% of EID-treated patients. Our model predicted that at least 9 NTZ infusions/year are required to maintain adequate trough saturation and concentration levels. Higher body mass index (BMI) was a predictor of suboptimal trough saturation on EID NTZ. CONCLUSIONS: Trough α4-integrin receptor saturation >50% correlated with high clinical efficacy of NTZ in previous studies. A continual treatment with EID maintains receptor saturation and concentration that are in the "therapeutic range" for most patients. This finding provides biological plausibility for the clinical efficacy of NTZ EID. Patients with higher BMI may require closer clinical and MRI follow-up.

Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing.

OBJECTIVE: To use the large dataset from the Tysabri Outreach: Unified Commitment to Health (TOUCH) program to compare progressive multifocal leukoencephalopathy (PML) risk with natalizumab extended interval dosing (EID) vs standard interval dosing (SID) in patients with multiple sclerosis (MS). METHODS: This retrospective cohort study included anti-JC virus antibody-positive patients (n = 35,521) in the TOUCH database as of June 1, 2017. The effect of EID on PML risk was evaluated with 3 planned analyses using Kaplan-Meier methods stratified by prior immunosuppressant use. Risk of PML was analyzed by Cox regression adjusted for age, sex, prior immunosuppressants, time since natalizumab initiation, and cumulative number of infusions. RESULTS: This study included 35,521 patients (primary analysis: 1,988 EID, 13,132 SID; secondary analysis: 3,331 EID, 15,424 SID; tertiary analysis: 815 EID, 23,168 SID). Mean average dosing intervals were 35.0 to 43.0 and 29.8 to 30.5 days for the EID and SID cohorts, respectively. Hazard ratios (95% confidence intervals) of PML risk for EID vs SID were 0.06 (0.01-0.22, p < 0.001) and 0.12 (0.05-0.29, p < 0.001) for the primary and secondary analyses, respectively. Relative risk reductions were 94% and 88% in favor of EID for the primary and secondary analyses, respectively. The tertiary analysis included no cases of PML with EID. CONCLUSION: Natalizumab EID is associated with clinically and statistically significantly lower PML risk than SID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, natalizumab EID is associated with a lower PML risk than SID.

Evaluation of natalizumab pharmacokinetics and pharmacodynamics with standard and extended interval dosing.

BACKGOUND: Natalizumab (NTZ) is a highly efficacious therapeutic for multiple sclerosis (MS), but treatment is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Extended interval dosing (EID) of NTZ has been proposed as an alternative dosing strategy to reduce PML risk. Pharmacokinetic (PK) and pharmacodynamic (PD) profiles of standard interval dosing (SID) and EID under real-world circumstances remain poorly characterized. OBJECTIVE: To evaluate PK and PD parameters of NTZ for SID and EID in the context of patient and treatment characteristics. METHODS: An observational cohort study was conducted to measure NTZ serum concentrations in MS patients at SID and EID nadir timepoints. NTZ occupancy of α4-integrin receptor sites, and cell surface expression of α4-integrin, was also measured. Patient body weight, age, and treatment exposure metrics were collected. RESULTS: NTZ serum concentrations were lower for EID than SID (mean = 18.2 versus 35.7 µg/ml, respectively; p < 0.001). Patient body weight, age, and treatment duration impacted concentrations with SID, though their influences were reduced or absent with EID. α4-integrin receptor occupancy by NTZ was lower for EID than SID (mean = 78.2 versus 87.4%, respectively; p < 0.001). Body weight impacted α4-integrin receptor occupancy differentially for EID versus SID. α4-integrin cell surface expression was modestly higher for EID than SID (267.2 versus 238.1 MFI, respectively; p < 0.001). CONCLUSIONS: EID of NTZ reduces nadir serum drug levels and α4-integrin receptor occupancy, as well as increases α4-integrin cell surface expression. The resulting increase in the number of open α4-intregrin receptors may enhance immune surveillance of JCV and prevention of PML. Body weight plays a significant role in the pharmacokinetic and pharmacodynamic responses to NTZ treatment. Further research is warranted to help establish pharmacological thresholds of NTZ efficacy and safety, which could help guide decision-making for dosing of NTZ.

Temporal response profiles of serum ubiquitin C-terminal hydrolase-L1 and the 145-kDa alpha II-spectrin breakdown product after severe traumatic brain injury in children.

OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of acquired disability among children. Brain injury biomarkers may serve as useful diagnostic and prognostic indicators for TBI. Levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and the 145-kDa alpha II-spectrin breakdown product (SBDP-145) correlate with outcome in adults after severe TBI. The authors conducted a pilot study of these biomarkers in children after severe TBI to inform future research exploring their utility in this population. METHODS: The levels of UCH-L1 and SBDP-145 were measured in serum, and UCH-L1 in CSF from pediatric patients after severe TBI over 5 days after injury. Both biomarkers were also measured in age-matched control serum and CSF. RESULTS: Adequate numbers of samples were obtained in serum, but not CSF, to assess biomarker temporal response profiles. Using patients with samples from all time points, UCH-L1 levels increased rapidly and transiently, peaking at 12 hours after injury. SBDP-145 levels showed a more gradual and sustained response, peaking at 48 hours. The median serum UCH-L1 concentration was greater in patients with TBI than in controls (median [IQR] = 361 [187, 1330] vs 147 [50, 241] pg/ml, respectively; p < 0.001). Receiver operating characteristic (ROC) analysis revealed an AUC of 0.77. Similarly, serum SBDP-145 was greater in children with TBI than in controls (median [IQR] = 172 [124, 257] vs 69 [40, 99] pg/ml, respectively; p < 0.001), with an ROC AUC of 0.85. When only time points of peak levels were used for ROC analysis, the discriminability of each serum biomarker increased (AUC for UCH-L1 at 12 hours = 1.0 and for SBDP-145 at 48 hours = 0.91). Serum and CSF UCH-L1 levels correlated well in patients with TBI (r = 0.70, p < 0.001). CONCLUSIONS: Findings from this exploratory study reveal robust increases of UCH-L1 and SBDP-145 in serum and UCH-L1 in CSF obtained from children after severe TBI. In addition, important temporal profile differences were found between these biomarkers that can help guide optimal time point selection for future investigations of their potential to characterize injury or predict outcomes after pediatric TBI.

Chair Lift Falls and Injuries in Children.

OBJECTIVE: The objective of this study was to compare demographic injury and treatment characteristics of hospitalized pediatric cases of falls from chair lifts to cases of other ski and snowboarding injuries and identify potential interventions for preventing falls from chair lifts. METHODS: Retrospective query of the trauma registry of Utah's only pediatric trauma center for children younger than 18 years requiring hospitalization for a ski or snowboarding injury from November 2004 to February 2014. RESULTS: There were 443 cases of hospitalized ski and snowboarding injuries during the study period. Twenty-nine cases (7%) fell from height while riding a chair lift. Children falling from chair lifts were more likely to be younger (6.9 years vs 12.1, P < 0.0001), female (41% vs 20%, P < 0.01), and elicit trauma team activation (72% vs 34%, P = <0.0001) but were less frequently treated in the operating room (14 vs 24%, P = 0.02) than children with other ski and snowboarding injuries. There were no differences in mortality, injury severity score, length of hospital stay, or airway intubation outside the operating room. When stated (11/29 cases), mean estimated height of fall from lift was 26 feet. The most common body region in chair lift falls with a significant injury (abbreviated injury scale, ≥3) was lower extremity (4/29, all femur fractures). Patient age discriminated chair lift falls well (area under the receiver operating characteristic curve, 0.87) with age of 7 years and below predicting chair lift fall with a sensitivity of 76% and a specificity of 91%. CONCLUSIONS: Injuries requiring hospitalization after falls from chair lifts occur at regulated facilities and are more common in younger female children when compared with other ski and snowboarding injuries. Interventions for reducing falls from chair lifts may be most effective applied to children 7 years and younger.

Preventable transfers in pediatric trauma: A 10-year experience at a level I pediatric trauma center.

BACKGROUND: Injured children are often treated at one facility then transferred to another that specializes in pediatric trauma care. The purpose of this study was to identify and characterize potentially preventable transfers (PT) to a freestanding level-I pediatric trauma center. METHODS: Children with traumatic injuries transferred between 2003 and 2013 were retrospectively analyzed. A PT was defined as a child who was discharged within 36hours of arrival without surgical intervention or advanced imaging studies. RESULTS: During this period, 6380 children were transferred, with head injury being the most common injury. 61% had CT imaging performed before transfer. The mean age was 6.9years, mean injury severity score (ISS) 10.4, and median transfer distance 37miles. 27% of these transfers were classified as PT. Air transport was used in 15% at mean charge of $18,574. 29% were discharged from the emergency department. When compared, PTs were younger (6.0 vs. 7.2years, p<0.001), with lower median ISS (5 vs. 9, p<0.001), shorter median LOS (15 vs. 43.6hours, p<0.001), and less PICU admissions (6% vs. 34%, p<0.001). CONCLUSION: A significant number of pediatric trauma transfers can be classified as preventable. Reducing preventable transfers could offer opportunities for improving value in a trauma care system.

Risk factors for traumatic blunt cerebrovascular injury diagnosed by computed tomography angiography in the pediatric population: a retrospective cohort study.

OBJECT Computed tomography angiography (CTA) is frequently used to examine patients for blunt cerebrovascular injury (BCVI) after cranial trauma, but the pediatric population at risk for BCVI is poorly defined. Although CTA is effective for BCVI screening in adults, the increased lifetime risk for malignant tumors associated with this screening modality warrants efforts to reduce its use in children. The authors' objective was to evaluate the incidence of BCVI diagnosed by CTA in a pediatric patient cohort and to create a prediction model to identify children at high risk for BCVI. METHODS Demographic, clinical, and radiographic data were collected retrospectively for pediatric patients who underwent CTA during examination for traumatic cranial injury from 2003 through 2013. The primary outcome was injury to the carotid or vertebral artery diagnosed by CTA. RESULTS The authors identified 234 patients (mean age 8.3 years, range 0.04-17 years, 150 [64%] boys) who underwent CTA screening for BCVI. Of these, 24 (10.3%) had a focal neurological deficit, and 153 (65.4%) had intracranial hemorrhage on a head CTA. Thirty-seven BCVIs were observed in 36 patients (15.4%), and 16 patients (6.8%) died. Multivariate regression analysis identified fracture through the carotid canal, petrous temporal bone fracture, Glasgow Coma Scale (GCS) score of < 8, focal neurological deficit, and stroke on initial CT scan as independent risk factors for BCVI. A prediction model for identifying children at high risk for BCVI was created. A score of ≤ 2 yielded a 7.9% probability of BCVI and a score of ≥ 3 a risk of 39.3% for BCVI. CONCLUSIONS For cranial trauma in children, fracture of the petrous temporal bone or through the carotid canal, focal neurological deficit, stroke, and a GCS score of < 8 are independent risk factors for BCVI.

Helicopter versus ground emergency medical services for the transportation of traumatically injured children.

BACKGROUND: Helicopter emergency medical services (HEMS) are a common mode of transportation for pediatric trauma patients. We hypothesized that HEMS improve outcomes for traumatically injured children compared to ground emergency medical services (GEMS). METHODS: We queried trauma registries of two level 1 pediatric trauma centers for children 0-17 years, treated from 2003 to 2013, transported by HEMS or GEMS, with known transport starting location and outcome. A geocoding service estimated travel distance and time. Multivariate regression analyses were performed to adjust for injury severity variables and travel distance/time. RESULTS: We identified 14,405 traumatically injured children; 3870 (26.9%) transported by HEMS and 10,535 (73.1%) transported by GEMS. Transport type was not significantly associated with survival, ICU length of stay, or discharge disposition. Transport by GEMS was associated with a 68.6%-53.1% decrease in hospital length of stay, depending on adjustment for distance/time. Results were similar for children with severe injuries, and with propensity score matched cohorts. Of note, 862/3850 (22.3%) of HEMS transports had an ISS<10 and hospitalization<1 day. CONCLUSIONS: HEMS do not independently improve outcomes for traumatically injured children, and 22.3% of children transported by HEMS are not significantly injured. These factors should be considered when requesting HEMS for transport of traumatically injured children.

Impact of newly adopted guidelines for management of children with isolated skull fracture.

PURPOSE: In an effort to standardize practices and reduce unnecessary hospital resource utilization, we implemented guidelines for management of patients with isolated skull fractures (ISF). We sought to examine the impact of these guidelines. METHODS: Patients with nondisplaced/depressed fracture of the skull vault without intracranial hemorrhage were prospectively enrolled from February 2010 to February 2014. RESULTS: Eighty-eight patients (median age=10months) were enrolled. Fall was the most common mechanism of injury (87%). The overall admission rate was 57%, representing an 18% decrease from that reported prior to guideline implementation (2003-2008; p=0.001). Guideline criteria for admission included vomiting, abnormal neurologic exam, concern for abuse, and others. Forty-two percent of patients were admitted outside of the guideline, primarily because of young age (20%). Patients transferred from another hospital (36%) were more likely to be admitted, though the majority (63%) did not meet admission criteria. No ED-discharged patient returned for neurologic symptoms, and none reported significant ongoing symptoms on follow-up phone call. CONCLUSIONS: Implementation of a new guideline for management of ISF resulted in a reduction of admissions without compromising patient safety. Young age remains a common concern for practitioners despite not being a criterion for admission. Interhospital transfer may be unnecessary in many cases.

Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.

After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI.

Use of Rotterdam CT scores for mortality risk stratification in children with traumatic brain injury.

OBJECTIVES: The Rotterdam CT score refined features of the Marshall score and was designed to categorize traumatic brain injury type and severity in adults. The objective of this study was to determine whether the Rotterdam CT score can be used for mortality risk stratification after pediatric traumatic brain injury. DESIGN: In children with moderate to severe traumatic brain injury, a comparison of observed versus predicted mortality was calculated using published model probabilities of adult mortality. Development and validation of a new pediatric mortality model using randomly selected prediction and validation samples from our cohort. SETTING: A single level 1 pediatric trauma center. SUBJECTS: Six hundred thirty-two children with moderate or severe traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen percent of the patients (101 of 632) died prior to hospital discharge. The predicted mortality based on Rotterdam score for adults with moderate or severe traumatic brain injury discriminated pediatric observed mortality well (area under the curve = 0.85; 95% CI, 0.80-0.89) but had poor calibration, overestimating or underestimating mortality for children in several Rotterdam categories. A predictive model based on children with moderate or severe traumatic brain injury from the single center discriminated mortality well (area under the curve, 0.80; 95% CI, 0.68-0.91) and showed good calibration and overall fit. CONCLUSIONS: Children with traumatic brain injury have better survival than adults in Rotterdam CT score categories representing less severe injuries but worse survival than adults in higher score categories. A novel, validated pediatric mortality model based on the Rotterdam score is accurate in children with moderate or severe traumatic brain injury and can be used for risk stratification.

Pediatric liver lacerations and intensive care: evaluation of ICU triage strategies.

OBJECTIVE: To compare PICU admission criteria following blunt traumatic liver laceration based on CT grade and/or physiologic instability with actual practice to improve efficiency of ICU admission. DESIGN: Retrospective cohort study. SETTING: Patients with grade 3-6 liver lacerations, 2002-2010. PATIENTS: Hundred seventy-one infants and children, ages 1 month to 17 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preadmission signs of physiologic instability (i.e., coma and cardiac arrest), liver CT grading, and outcomes including length of stay and packed RBC transfusion after admission to ICU were collected. Multiple body region severe trauma was defined as more than or equal to 1 extra-abdominal body area abbreviated injury score more than or equal to 4. Actual ICU admissions were compared with predicted. Two patients died before ICU admission and five (3%) died afterward. Of 169 patients, 52 (31%) were initially admitted to the inpatient ward. Five percent received surgical care for liver injury. Twenty percent received packed RBCs emergently for shock, whereas 5% received their first packed RBCs after admission. Compared with ICU admissions, ward patients were significantly older, had lower Injury Severity Scores, and less operative care. Among ICU patients, transfusion for hemorrhagic shock was significantly associated with more severe injury scores. Sixty percent of ICU patients were not transfused. ICU triage determined by signs of physiologic instability predicted 53 admissions (31%) including seven of nine patients (78%) treated with transfusions after admission. Predicted ICU admission for nontransfused patients was lower-9%. Adding CT laceration grade more than or equal to 4 increased ICU admissions to 129 (76%). Among surviving ICU patients, 37 of 62 patients (60%) with isolated severe abdominal trauma and no systemic instability had ICU length of stay less than 1 day. CONCLUSIONS: Children with isolated abdominal injury and no physiologic instability can generally be treated without ICU admission. Adding grade more than or equal to 4 to usual ICU admission criteria resulted in excessive admission of stable patients.

Cervical spine computed tomography utilization in pediatric trauma patients.

BACKGROUND: Guidelines for evaluating the cervical spine in pediatric trauma patients recommend cervical spine CT (CSCT) when plain radiographs suggest an injury. Our objective was to compare usage of CSCT between a pediatric trauma center (PTC) and referral general emergency departments (GEDs). METHODS: Patient data from a pediatric trauma registry from 2002 to 2011 were analyzed. Rates of CSI and CSCT of patients presenting to the PTC and GED were compared. Factors associated with use of CSCT were assessed using multivariate logistic regression. RESULTS: 5148 patients were evaluated, 2142 (41.6%) at the PTC and 3006 (58.4%) at the GED. Groups were similar with regard to age, gender, GCS, and triage category. GED patients had a higher median ISS (14 vs. 9, p<0.05) and more frequent ICU admissions (44.3% vs. 26.1% p<0.05). CSI rate was 2.1% (107/5148) and remained stable. CSCT use increased from 3.5% to 16.1% over time at the PTC (mean 9.6% 95% CI=8.3, 10.9) and increased from 6.8% to 42.0% (mean 26.9%, CI=25.4, 28.4) at the GED. Initial care at a GED remained strongly associated with CSCT. CONCLUSIONS: Despite a stable rate of CSI, rate of CSCT increased significantly over time, especially among patients initially evaluated at a GED.

Fecal continence following complex anorectal trauma in children.

BACKGROUND: Complex injuries involving the anus and rectum are uncommon in children. We sought to examine long-term fecal continence following repair of these injuries. METHODS: We conducted a retrospective review using our trauma registry from 2003 to 2012 of children with traumatic injuries to the anus or rectum at a level I pediatric trauma center. Patients with an injury requiring surgical repair that involved the anal sphincters and/or rectum were selected for a detailed review. RESULTS: Twenty-one patients (21/13,149 activations, 0.2%) who had an injury to the anus (n=9), rectum (n=8), or destructive injury to both the anus and rectum (n=4) were identified. Eleven (52%) patients were male, and the median age at time of injury was 9 (range 1-14) years. Penetrating trauma accounted for 48% of injuries. Three (14%) patients had accompanying injury to the urinary tract, and 6 (60%) females had vaginal injuries. All patients with an injury involving the rectum and destructive anal injuries were managed with fecal diversion. No patient with an isolated anal injury underwent fecal diversion. Four (19%) patients developed wound infections. The majority (90%) of patients were continent at last follow-up. One patient who sustained a gunshot injury to the pelvis with sacral nerve involvement is incontinent, but remains artificially clean on an intense bowel management program with enemas, and one patient with a destructive crush injury still has a colostomy. CONCLUSIONS: With anatomic reconstruction of the anal sphincter mechanism, most patients with traumatic anorectal injuries will experience long-term fecal continence. Follow-up is needed as occasionally these patients, specifically those with nerve or crush injury, may require a formal bowel management program.

The role of focused abdominal sonography for trauma (FAST) in pediatric trauma evaluation.

PURPOSE: With increasing concerns about radiation exposure, we questioned whether a structured program of FAST might decrease CT use. METHODS: All pediatric trauma surgeons in our level 1 pediatric trauma center underwent formal FAST training. Children with potential abdominal trauma and no prior imaging were prospectively evaluated from 10/2/09 to 7/31/11. After physical exam and FAST, the surgeon declared whether the CT could be eliminated. RESULTS: Of 536 children who arrived without imaging, 183 had potential abdominal trauma. FAST was performed in 128 cases and recorded completely in 88. In 48% (42/88) the surgeon would have elected to cancel the CT based on the FAST and physical exam. One of the 42 cases had a positive FAST and required emergent laparotomy; the others were negative. The sensitivity of FAST for injuries requiring operation or blood transfusion was 87.5%. The sensitivity, specificity, PPV, and NPV in detecting pathologic free fluid were 50%, 85%, 53.8%, and 87.9%. CONCLUSIONS: True positive FAST exams are uncommon and would rarely direct management. While the negative FAST would have potentially reduced CT use due to practitioner reassurance, this reassurance may be unwarranted given the test's sensitivity.

High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury.

OBJECTIVES: To evaluate high-dose barbiturates as a second-tier therapy for pediatric refractory intracranial hypertension complicating severe traumatic brain injury. DESIGN: This is a retrospective cohort study of children with refractory intracranial hypertension treated with high-dose barbiturates. SETTING: A single center level I pediatric trauma from 2001 to 2010. PATIENTS: Thirty-six children with refractory intracranial hypertension defined as intracranial pressure greater than 20 mm Hg despite standard management treated with high-dose barbiturates after severe traumatic brain injury. INTERVENTIONS: High-dose barbiturates were administered for refractory intracranial hypertension for a minimum duration of 6 hours and monitored by continuous electroencephalography. MEASUREMENTS AND MAIN RESULTS: Exposure was control of refractory intracranial hypertension defined as > 20 mm Hg within 6 hours after starting barbiturates. Pediatric cerebral performance category scores at hospital discharge and at 3 months (or longer) follow-up were the primary outcomes. Ten of 36 patients (28%) had control of refractory intracranial hypertension. Neither demographic nor injury characteristics were associated with refractory intracranial hypertension control. Children who responded received barbiturates significantly later after injury (76 vs. 29 median hours). Overall, 14 children died, 13 without control of intracranial pressure. Survival was more common in those who responded compared with those who did not respond to high-dose barbiturates, although this did not reach statistical significance (relative risk of death 0.2; 95% confidence interval; [0.03-1.3]). Of the 22 survivors, 19 had an acceptable survival (pediatric cerebral performance category less than 3) at 3 months or longer after injury; however, only three returned to normal function. Among survivors, control of refractory intracranial hypertension was associated with significantly better pediatric cerebral performance category scores and over two-fold likelihood of acceptable long-term outcome (relative risk 2.3; 95% confidence interval [1.4-4.0]) compared with uncontrolled refractory intracranial hypertension despite high-dose barbiturates. CONCLUSIONS: Addition of high-dose barbiturates achieved control of refractory intracranial hypertension in almost 30% of treated children. Control of refractory intracranial hypertension was associated with increased likelihood of an acceptable long-term outcome.

Neurologically intact children with an isolated skull fracture may be safely discharged after brief observation.

PURPOSE: The management of children presenting with an isolated skull fracture (ISF) posttrauma is highly variable. We sought to estimate the risk of neurologic deterioration in children with a Glasgow coma score (GCS) 15 and ISF to reduce unnecessary hospital admissions. METHODS: A retrospective review at a level I pediatric trauma referral center was conducted for patients with ISF on head computed tomography from 2003 to 2008. Patients were excluded for injury greater than 24 hours prior, GCS less than 15, intracranial pathology, significant fracture depression, or complex fractures involving facial bones or skull base. RESULTS: A total of 235 patients were identified with an ISF. The median age was 11 months, with falls accounting for 87% of the injuries. One hundred seventy-seven patients were admitted, and 58 patients were discharged from the emergency department after a period of observation (median, 3.3 hours). Median length of stay for those admitted to the hospital was 18.2 hours. One patient developed vomiting following overnight observation and a repeat computed tomography scan demonstrated a small extra-axial hematoma that required no intervention. The mean total costs for patients discharged from the emergency department were $291 vs $1447 for those admitted for observation (P < .001). CONCLUSION: Patients with a presenting GCS of 15 and an ISF can be safely discharged from the emergency department after a short period of observation if they are asymptomatic and have a reliable social environment. This could result in significant savings by eliminating inpatient costs.

Use of focused abdominal sonography for trauma at pediatric and adult trauma centers: a survey.

PURPOSE: Focused abdominal sonography for trauma (FAST) has been popularized for the initial evaluation of trauma patients. We sought to understand the scope of practice on a national level with specific attention to its use in the pediatric age group. METHODS: An electronic survey was sent to all American College of Surgeons level I trauma centers and the National Association of Children's Hospitals and Related Institutions that were freestanding children's hospitals. RESULTS: The survey was emailed to 124 centers, and 98 (79%) completed the survey. Of the surveyed centers, 23% cared for adults only, 28% were freestanding children's hospitals, and 49% managed both. At adults-only institutions, 96% use FAST and at children's hospitals, only 15%; it is used at 85% of centers that care for both. For the centers that use FAST on children, 88% have no age limit. Of all the institutions that typically use FAST, the individual performing the examination could be a surgeon (73%), an emergency department doctor (48%), or a radiologist (3%). Of the centers that perform FAST, 51% bill for the FAST examination. CONCLUSIONS: Adult hospitals are much more likely to perform FAST examinations in the trauma patient, and many adult centers routinely use FAST to examine pediatric patients.

Clinical clearance of the cervical spine in blunt trauma patients younger than 3 years: a multi-center study of the american association for the surgery of trauma.

BACKGROUND: Cervical spine clearance in the very young child is challenging. Radiographic imaging to diagnose cervical spine injuries (CSI) even in the absence of clinical findings is common, raising concerns about radiation exposure and imaging-related complications. We examined whether simple clinical criteria can be used to safely rule out CSI in patients younger than 3 years. METHODS: The trauma registries from 22 level I or II trauma centers were reviewed for the 10-year period (January 1995 to January 2005). Blunt trauma patients younger than 3 years were identified. The measured outcome was CSI. Independent predictors of CSI were identified by univariate and multivariate analysis. A weighted score was calculated by assigning 1, 2, or 3 points to each independent predictor according to its magnitude of effect. The score was established on two thirds of the population and validated using the remaining one third. RESULTS: Of 12,537 patients younger than 3 years, CSI was identified in 83 patients (0.66%), eight had spinal cord injury. Four independent predictors of CSI were identified: Glasgow Coma Score <14, GCSEYE = 1, motor vehicle crash, and age 2 years or older. A score of <2 had a negative predictive value of 99.93% in ruling out CSI. A total of 8,707 patients (69.5% of all patients) had a score of <2 and were eligible for cervical spine clearance without imaging. There were no missed CSI in this study. CONCLUSIONS: CSI in patients younger than 3 years is uncommon. Four simple clinical predictors can be used in conjunction to the physical examination to substantially reduce the use of radiographic imaging in this patient population.