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Pawel G. Ochalski, David O. Okonkwo, Michael J. Bell and P. David Adelson

The authors report on a case of successful reversal of sedation with flumazenil, a benzodiazepine antagonist, in a child following a moderate traumatic brain injury and demonstrate the utility of flumazenil to reverse benzodiazepine effects in traumatically injured children.

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Stacy A. Shackelford, Deborah J. del Junco, Michael C. Reade, Randy Bell, Tyson Becker, Jennifer Gurney, Randall McCafferty and Donald W. Marion

OBJECTIVE

In combat and austere environments, evacuation to a location with neurosurgery capability is challenging. A planning target in terms of time to neurosurgery is paramount to inform prepositioning of neurosurgical and transport resources to support a population at risk. This study sought to examine the association of wait time to craniectomy with mortality in patients with severe combat-related brain injury who received decompressive craniectomy.

METHODS

Patients with combat-related brain injury sustained between 2005 and 2015 who underwent craniectomy at deployed surgical facilities were identified from the Department of Defense Trauma Registry and Joint Trauma System Role 2 Registry. Eligible patients survived transport to a hospital capable of diagnosing the need for craniectomy and performing surgery. Statistical analyses included unadjusted comparisons of postoperative mortality by elapsed time from injury to start of craniectomy, and Cox proportional hazards modeling adjusting for potential confounders. Time from injury to craniectomy was divided into quintiles, and explored in Cox models as a binary variable comparing early versus delayed craniectomy with cutoffs determined by the maximum value of each quintile (quintile 1 vs 2–5, quintiles 1–2 vs 3–5, etc.). Covariates included location of the facility at which the craniectomy was performed (limited-resource role 2 facility vs neurosurgically capable role 3 facility), use of head CT scan, US military status, age, head Abbreviated Injury Scale score, Injury Severity Score, and injury year. To reduce immortal time bias, time from injury to hospital arrival was included as a covariate, entry into the survival analysis cohort was defined as hospital arrival time, and early versus delayed craniectomy was modeled as a time-dependent covariate. Follow-up for survival ended at death, hospital discharge, or hospital day 16, whichever occurred first.

RESULTS

Of 486 patients identified as having undergone craniectomy, 213 (44%) had complete date/time values. Unadjusted postoperative mortality was 23% for quintile 1 (n = 43, time from injury to start of craniectomy 30–152 minutes); 7% for quintile 2 (n = 42, 154–210 minutes); 7% for quintile 3 (n = 43, 212–320 minutes); 19% for quintile 4 (n = 42, 325–639 minutes); and 14% for quintile 5 (n = 43, 665–3885 minutes). In Cox models adjusted for potential confounders and immortal time bias, postoperative mortality was significantly lower when time to craniectomy was within 5.33 hours of injury (quintiles 1–3) relative to longer delays (quintiles 4–5), with an adjusted hazard ratio of 0.28, 95% CI 0.10–0.76 (p = 0.012).

CONCLUSIONS

Postoperative mortality was significantly lower when craniectomy was initiated within 5.33 hours of injury. Further research to optimize craniectomy timing and mitigate delays is needed. Functional outcomes should also be evaluated.

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M. Benjamin Larkin, Erin K. M. Graves, Jason H. Boulter, Nicholas S. Szuflita, R. Michael Meyer, Michael E. Porambo, John J. Delaney and Randy S. Bell

OBJECTIVE

There are limited data concerning the long-term functional outcomes of patients with penetrating brain injury. Reports from civilian cohorts are small because of the high reported mortality rates (as high as 90%). Data from military populations suggest a better prognosis for penetrating brain injury, but previous reports are hampered by analyses that exclude the point of injury. The purpose of this study was to provide a description of the long-term functional outcomes of those who sustain a combat-related penetrating brain injury (from the initial point of injury to 24 months afterward).

METHODS

This study is a retrospective review of cases of penetrating brain injury in patients who presented to the Role 3 Multinational Medical Unit at Kandahar Airfield, Afghanistan, from January 2010 to March 2013. The primary outcome of interest was Glasgow Outcome Scale (GOS) score at 6, 12, and 24 months from date of injury.

RESULTS

A total of 908 cases required neurosurgical consultation during the study period, and 80 of these cases involved US service members with penetrating brain injury. The mean admission Glasgow Coma Scale (GCS) score was 8.5 (SD 5.56), and the mean admission Injury Severity Score (ISS) was 26.6 (SD 10.2). The GOS score for the cohort trended toward improvement at each time point (3.6 at 6 months, 3.96 at 24 months, p > 0.05). In subgroup analysis, admission GCS score ≤ 5, gunshot wound as the injury mechanism, admission ISS ≥ 26, and brain herniation on admission CT head were all associated with worse GOS scores at all time points. Excluding those who died, functional improvement occurred regardless of admission GCS score (p < 0.05). The overall mortality rate for the cohort was 21%.

CONCLUSIONS

Good functional outcomes were achieved in this population of severe penetrating brain injury in those who survived their initial resuscitation. The mortality rate was lower than observed in civilian cohorts.

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Peter A. Ferrazzano, Bedda L. Rosario, Stephen R. Wisniewski, Nadeem I. Shafi, Heather M. Siefkes, Darryl K. Miles, Andrew L. Alexander, Michael J. Bell and for the Investigators of the ADAPT Trial

OBJECTIVE

There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI.

METHODS

Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI.

RESULTS

Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common.

CONCLUSIONS

Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.

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Martina Stippler, Veronica Ortiz, P. David Adelson, Yue-Fang Chang, Elizabeth C. Tyler-Kabara, Stephen R. Wisniewski, Ericka L. Fink, Patrick M. Kochanek, S. Danielle Brown and Michael J. Bell

Object

Minimizing secondary brain injuries after traumatic brain injury (TBI) in children is critical to maximizing neurological outcome. Brain tissue oxygenation monitoring (as measured by interstitial partial pressure of O2 [PbO2]) is a new tool that may aid in guiding therapies, yet experience in children is limited. This study aims to describe the authors' experience of PbO2 monitoring after TBI. It was hypothesized that PbO2 thresholds could be established that were associated with favorable neurological outcome, and it was determined whether any relationships between PbO2 and other important clinical variables existed.

Methods

Forty-six children with severe TBI (Glasgow Coma Scale score ≤ 8 after resuscitation) who underwent PbO2 and brain temperature monitoring between September 2004 and June 2008 were studied. All patients received standard neurocritical care, and 24 were concurrently enrolled in a trial of therapeutic early hypothermia (n = 12/group). The PbO2 was measured in the uninjured frontal cortex. Hourly recordings and calculated daily means of various variables including PbO2, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure, partial pressure of arterial O2, and fraction of inspired O2 were compared using several statistical approaches. Glasgow Outcome Scale scores were determined at 6 months after injury.

Results

The mean patient age was 9.4 years (range 0.1–16.5 years; 13 girls) and 8554 hours of monitoring were analyzed (PbO2 range 0.0–97.2 mm Hg). A PbO2 of 30 mm Hg was associated with the highest sensitivity/specificity for favorable neurological outcome at 6 months after TBI, yet CPP was the only factor that was independently associated with favorable outcome. Surprisingly, instances of preserved PbO2 with altered ICP and CPP were observed in some children with unfavorable outcomes.

Conclusions

Monitoring of PbO2 demonstrated complex interactions with clinical variables reflecting intracranial dynamics using this protocol. A higher threshold than reported in studies in adults was suggested as a potential therapeutic target, but this threshold was not associated with improved outcomes. Additional studies to assess the utility of PbO2 monitoring after TBI in children are needed.

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R. Michael Meyer, M. Benjamin Larkin, Nicholas S. Szuflita, Chris J. Neal, Jeffrey M. Tomlin, Rocco A. Armonda, Jeffrey A. Bailey and Randy S. Bell

OBJECTIVE

Traumatic brain injury (TBI) is independently associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). Given the numerous studies of civilian closed-head injury, the Brain Trauma Foundation recommends venous thromboembolism chemoprophylaxis (VTC) after severe TBI. No studies have specifically examined this practice in penetrating brain injury (PBI). Therefore, the authors examined the safety and effectiveness of early VTC after PBI with respect to worsening intracranial hemorrhage and DVT or PE.

METHODS

The Kandahar Airfield neurosurgery service managed 908 consults between January 2010 and March 2013. Eighty of these were US active duty members with PBI, 13 of whom were excluded from analysis because they presented with frankly nonsurvivable CNS injury or they died during initial resuscitation. This is a retrospective analysis of the remaining 67 patients.

RESULTS

Thirty-two patients received early VTC and 35 did not. Mean time to the first dose was 24 hours. Fifty-two patients had blast-related PBI and 15 had gunshot wounds (GSWs) to the head. The incidence of worsened intracranial hemorrhage was 16% after early VTC and 17% when it was not given, with the relative risk approaching 1 (RR = 0.91). The incidence of DVT or PE was 12% after early VTC and 17% when it was not given (RR = 0.73), though this difference was not statistically significant.

CONCLUSIONS

Early VTC was safe with regard to the progression of intracranial hemorrhage in this cohort of combat-related PBI patients. Data in this study suggest that this intervention may have been effective for the prevention of DVT or PE but not statistically significantly so. More research is needed to clarify the safety and efficacy of this practice.

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Paige J. Ostahowski, Nithya Kannan, Mark S. Wainwright, Qian Qiu, Richard B. Mink, Jonathan I. Groner, Michael J. Bell, Christopher C. Giza, Douglas F. Zatzick, Richard G. Ellenbogen, Linda Ng Boyle, Pamela H. Mitchell, Monica S. Vavilala and for the PEGASUS (Pediatric Guideline Adherence and Outcomes) Study

OBJECTIVE

Posttraumatic seizure is a major complication following traumatic brain injury (TBI). The aim of this study was to determine the variation in seizure prophylaxis in select pediatric trauma centers. The authors hypothesized that there would be wide variation in seizure prophylaxis selection and use, within and between pediatric trauma centers.

METHODS

In this retrospective multicenter cohort study including 5 regional pediatric trauma centers affiliated with academic medical centers, the authors examined data from 236 children (age < 18 years) with severe TBI (admission Glasgow Coma Scale score ≤ 8, ICD-9 diagnosis codes of 800.0–801.9, 803.0–804.9, 850.0–854.1, 959.01, 950.1–950.3, 995.55, maximum head Abbreviated Injury Scale score ≥ 3) who received tracheal intubation for ≥ 48 hours in the ICU between 2007 and 2011.

RESULTS

Of 236 patients, 187 (79%) received seizure prophylaxis. In 2 of the 5 centers, 100% of the patients received seizure prophylaxis medication. Use of seizure prophylaxis was associated with younger patient age (p < 0.001), inflicted TBI (p < 0.001), subdural hematoma (p = 0.02), cerebral infarction (p < 0.001), and use of electroencephalography (p = 0.023), but not higher Injury Severity Score. In 63% cases in which seizure prophylaxis was used, the patients were given the first medication within 24 hours of injury, and 50% of the patients received the first dose in the prehospital or emergency department setting. Initial seizure prophylaxis was most commonly with fosphenytoin (47%), followed by phenytoin (40%).

CONCLUSIONS

While fosphenytoin was the most commonly used medication for seizure prophylaxis, there was large variation within and between trauma centers with respect to timing and choice of seizure prophylaxis in severe pediatric TBI. The heterogeneity in seizure prophylaxis use may explain the previously observed lack of relationship between seizure prophylaxis and outcomes.

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Stephen J. Whitaker, Eric M. Bessell, Sue E. Ashley, H. J. G. Bloom, B. Anthony Bell and Michael Brada

✓ Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade 1 and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p < 0.005, 95% confidence interval 2.7 to 30).

The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p < 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery. 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma.