Dexamethasone Use in Pediatric Neurosurgical Trauma: A Systematic Review and Proportional Meta-Analysis of the Current Literature

Dexamethasone Use in Pediatric Neurosurgical Trauma: A Systematic Review and Proportional Meta-Analysis of the Current Literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Dexamethasone Use in Pediatric Neurosurgical Trauma: A Systematic Review and Proportional Meta-Analysis of the Current Literature Ezinwa Kalunta-Crumpton, Sanjay Neerukonda, Parker Smith, Peace Odiase, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7467090/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Study Design: Systematic Review with Proportional Meta-Analysis Objectives: Dexamethasone use in pediatric neurosurgical trauma remains controversial, with varying reports of its overall efficacy. Our study aims to assess the use of dexamethasone in pediatric neurosurgery regarding patient characteristics, risk factors, and dosing. Methods: A systematic review was conducted using PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify literature presenting dexamethasone use in pediatric neurosurgical trauma. Results: A total of 597 publications were identified, of which 13 met inclusion criteria (2 case reports, 11 retrospective studies). Case reports (N=4 patients, mean age 13.5 years) demonstrated traumatic brain injury with cerebral edema, hematoma, or swelling. All patients received dexamethasone (5–7 days), experienced no treatment-related complications, and 75% showed neurological improvement. Across 11 retrospective studies (N=493 patients, mean age 7.3 years), most presented with severe TBI and cerebral edema. Management strategies included conservative therapy (83%) or surgical intervention (13%). Dexamethasone was used in 61% of patients (average 0.92 mg/kg/day for 4.7 days). Reported outcomes were mixed: some studies demonstrated reduced mortality, improved neurological recovery, and lower ICP with dexamethasone, while others reported increased infection risk, catabolic effects, and no significant benefit. Pooled subgroup analysis showed patients who improved neurologically were more likely to have received dexamethasone (80.6% vs. 58.7%, p = 0.0347), whereas those who declined were less likely to have received it (19.4% vs. 41.3%, p = 0.0347). Infection was more common in dexamethasone-treated patients (52.0% vs. 16.7%, p = 0.0049). Conclusion: Evidence regarding dexamethasone use in pediatric traumatic brain injury is conflicting. Although some older studies suggest benefits including reduced ICP and mortality, most studies report limited efficacy and increased complications such as hyperglycemia, hypertension, gastrointestinal bleeding, and infections. Given the small number of available studies, no definitive recommendation can be made at this time. Further high-quality research is needed to clarify its role and establish guidelines for use in pediatric neurosurgical trauma. Dexamethasone Trauma Neurosurgery TBI Pediatric Conservative Steroid Figures Figure 1 INTRODUCTION Traumatic brain injury (TBI) is a leading cause of injury in children with a report detailing 475,000 cases in the United States each year. 14 Following an initial insult, TBI patients may undergo an expansion of intracranial volume leading to secondary injury. According to the Monro-Kellie hypothesis, intracranial space is composed of brain tissue, cerebrospinal fluid (CSF), and blood. Expansion of one of these components, or introduction of a new material, will result in an increase in the intracranial pressure (ICP) and/or a reflexive decrease in the volume of one of the other compartments. One of the goals of TBI management is to maintain homeostasis of all three intracranial components to protect cerebral blood flow and to preserve cerebral perfusion. 21 Neurosurgical trauma in children presents a set of challenges unique to the pediatric population. Because the skull is developing, pediatric patients have greater cranial plasticity/deformability, altering the biomechanical response to impact. 9 Despite this, developing pediatric brains are not fully myelinated, increasing susceptibility to traumatic forces in the unmyelinated regions of the brain. 10 Although there is significant variation between institutions in TBI treatment, management of pediatric TBI, after careful attention to airway, breathing, and circulation (ABCs), commonly begins with ICP monitoring. 19 Recent studies have suggested that ICP monitoring in severe TBI patients reduces deaths and improves survival. 1 , 2 The goal of ICP monitoring is to guide physicians in maintaining cerebral perfusion pressure (CPP). This is accomplished by reducing intracranial volume which has been shown to be essential for positive outcomes in children. 4 , 5 To maintain CPP within normal limits, medical and surgical management may include sedatives and analgesics for anesthesia, hyperosmolar therapy, CSF drainage, hyperventilation, barbiturates, craniotomy for evacuation of hematomas, decompressive craniectomy, and corticosteroids. 21 , 50 Indications for corticosteroids in neurosurgical trauma remain a source of controversy with varying reports as to their efficacy in the treatment of spinal, peripheral nerve, and cranial trauma. 3 , 7 , 8 , 11 , 15 Dexamethasone, a commonly used corticosteroid, is thought by some to mitigate deleterious effects of secondary injury following trauma by reducing inflammation around peripheral nerves and the brain therefore decreasing ICP in TBI. 7 , 13 Corticosteroids are hypothesized to restore vascular permeability, reduce edema/CSF production, and diminish free-radical injury. However, a large randomized trial in adults found no significant improvement in morbidity and mortality when patients were given corticosteroids following a TBI. 6 Following this study, Clinical Practice Guidelines for adult TBI recommended against the use of high-dose dexamethasone in adult TBI. 46 Despite significant study in adults, there is little evidence as to the efficacy of dexamethasone in the setting of pediatric neurosurgical trauma. According to the latest edition of the Brain Trauma Foundation Guidelines for the management of pediatric severe TBI, there was a weak recommendation (level III) stating that the use of steroids was not suggested to improve outcome or reduce ICP. Only two very old and small studies were included to support the recommendation. 51 Here we provide a review of the literature published on the use of dexamethasone in pediatric neurosurgical trauma. The objectives of this review are to 1) provide the first systematic review and proportional meta-analysis of current literature on the use of dexamethasone in the management of pediatric TBI, 2) highlight patient characteristics, risk factors, and dexamethasone dosing in pediatric neurosurgical TBI, and 3) provide guidance on the use of dexamethasone in pediatric TBI. METHODS Contributing Authors Seven authors contributed to this project: Ezinwa Kalunta-Crumpton (Corresponding Author, The University of Texas Southwestern Medical Center, Dallas, United States; [email protected] ) performed data collection, conducted article review, wrote the main manuscript text, and prepared all tables and figures. Sanjay Neerukonda (The University of Texas Health Science Center at Houston, Houston, United States; [email protected] ) assisted with data collection and edited abstract. Parker Smith (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected] ) assisted with data collection and wrote the introduction. Peace Odiase (Meharry Medical College, Nashville, United States; [email protected] ) performed all statistical analyses of the collected data. Abigail Jenkins (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected] ) supported manuscript completion by coordinating assignments and ensuring deadlines were met. Umaru Barrie (New York University Langone Medical Center, New York, United States; [email protected] ) conceived the manuscript topic and organized the research team. Bruno Braga (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected] ) reviewed and edited the entire manuscript prior to submission. Search Strategy We conducted our literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 16 We queried the online database PubMed on December 1st, 2023. The key search terms were “dexamethasone AND pediatric AND trauma”. Other terms included “neurosurgery” OR “children” OR “management” OR “outcomes”. Exclusion criteria were as follows: adult (> 18 years old) patient population, articles not written in English, literature reviews, correspondences, commentaries, book chapters, animal studies and opinion pieces. Other exclusion criteria included incomplete reporting of primary outcomes, surgical management not specified, studies with overlapping study populations, and the following etiologies: spinal cord injury, peripheral neuropathies, infection, tumor; only TBI was included. The objective of the study was to discuss, analyze, and examine all original articles exploring recommendations and outcomes in pediatric patients with neurosurgical trauma in which dexamethasone was used as a part of the medical management. Data Extraction Three authors (E.K.C [Corresponding Author], S.V.N, P.S.) independently performed the data extraction according to the search strategy. Discrepancies in inclusion criteria or collected data were evaluated by the authors and discussed to find a resolution. Identified articles were first screened by title, followed by abstracts and full texts to determine inclusion. An in-depth full-text review of all case studies and retrospective reviews was performed for the extraction of relevant data. Relevant data included research aim, population demographic, clinical characteristics, underlying conditions and predispositions, management, outcomes, and recommendations. Our data extraction and analysis incorporated demographic of patient population, patient presentation, underlying conditions or familial history, type of trauma, imaging modality and findings, dexamethasone dosing and duration, conservative or surgical management, other steroids used, complications related to dexamethasone, neurological outcome, and follow-up duration. Statistical Analysis We evaluated the distribution of our population characteristics with descriptive statistics. We assessed the occurrence of the objective based on the reported data. We predetermined the following characteristics of interest: average age, ratio of female to male patients, presenting signs and symptoms, physical exam findings, diagnostic modality, trauma type, dexamethasone dose and duration, form of intervention, and patient outcomes. Proportional Meta-Analysis Analyses were performed in R (version 4.3.x) using RStudio with the metafor, meta, and metadat packages. Given the expected high variability among the included studies, a random-effects model (REM) was employed for data aggregation. Heterogeneity across studies was assessed using Cochran’s Q statistic, and the I² test was applied to quantify the extent of heterogeneity. Additionally, 95% prediction intervals were calculated to estimate the range within which the true effect size is likely to fall in future studies, accounting for between-study variability. Forest plots were used to visually represent proportions. Subgroup analyses were conducted to examine how different population categories might impact the pooled proportions. Summary estimates between two independent subgroup meta-analyses were compared using a Wald-type test to determine significant differences. For categorical data, frequencies and percentages were calculated based on individual studies, while continuous data were summarized by calculating means and standard deviations from pooled data. Descriptive statistics were reported based on the available data from each study. Transparency was ensured by clearly stating the number of studies from which data were successfully extracted and detailing the patient count for each variable of interest relative to the total patient population within each study. A narrative summary was provided to report the challenges encountered and the proposed solutions identified in the literature. Of note, we excluded categories that were not mentioned in more than one paper (any categories where N = 1; see Table 2 and Table 3 ). RESULTS Electronic Search Yield Following the employment of PRISMA guidelines, our initial literature search produced 597 publications ( Fig. 1 ). Publications were excluded based on the criteria (n = 556), leaving 41 articles for preliminary review. An additional 28 articles were excluded following full-text review, producing a final total of 13 articles. Of the 13 articles, 2 were case reports ( Supplemental Table 1 ) and 11 were retrospective reviews ( Supplemental Table 2 ). Case Reports: Patient Characteristics Table 1 outlines patient demographics, presentation, management, and clinical outcome for all case reports included in the systematic review. Four patients (3 males, 1 female) were identified for analysis, with a mean age of 13.5 ± 4.65 years. All patients presented with traumatic brain injury. Diagnostic modalities varied between radiographs (25%), CT (100%), and MRI (25%). Radiologic findings included fractures and/or dislocations (25%), cerebral edema and/or swelling (50%), and hematoma and/or hemorrhage (50%). Table 1 Patient demographics, presentation, management, and outcomes for case reports Category Details Patient Demographics Age: 13.5 ± 4.65 years Sex: Male 3 (75%), Female 1 (25%) Presenting Symptoms • Visual disturbances: 1 (25%) • Dizziness: 1 (25%) • Motor deficits: 2 (50%) • Altered mental status: 3 (75%) Management Surgical: 0 (0%) Conservative: 4 (100%) Dexamethasone Therapy • Patients receiving: 4 (100%) • Dose: 8–80 mg, 3–4 times/day • Duration: 5–7 days • Route: IV 1 (25%), IM 0 (0%), PO 0 (0%) • Indication: Edema/inflammatory changes 4 (100%) Physical Examination GCS Score: 7–10 Imaging Modality CT: 4 (100%) X-Ray: 1 (25%) MRI: 1 (25%) Radiologic Findings • Edema/Swelling: 2 (50%) • Hematoma/Hemorrhage: 2 (50%) • Fracture: 1 (25%) Follow-Up / Outcomes Follow-Up: 3 months Neurologic Outcome: Improvement 3 (75%), Neutral 1 (25%), Deterioration 0 (0%) Patient Course: Improved 4 (100%), Worsened 0 (0%) Complications None reported Table 2 Overall Descriptives for Retrospective Studies Category Variable Prevalence (%) [95% CI] N (Studies) Total Patients Age Average Age 7.33 [6.67–7.99] 13 278 Gender Male 68.15 [45.91–90.39] 4 89 Female 31.85 [9.61–54.09] 4 89 Presenting Symptoms Visual Disturbances 71.36 [33.09–100] 4 338 Sensory Deficits 90.12 [71.40–100] 4 338 Motor Deficits 90.87 [79.49–100] 6 347 Altered Mental Status 99.64 [99.02–100] 6 347 Physical Exam Findings Comatose 99.64 [99.02–100] 6 347 GCS Score 8.08 [5.55–10.62] 8 89 Diagnostic Modality CT 99.55 [98.93–100] 9 443 Radiologic Findings Fracture 53.40 [38.40–68.40] 5 102 Edema/Swelling 78.45 [48.42–100] 4 338 Hematoma/Hemorrhage 19.05 [11.10–27.00] 7 331 Patient Management Surgical Management 13.32 [7.65–19.00] 6 126 Conservative Management (Dexamethasone) 82.97 [68.79–97.14] 17 288 Combined Surgical & Conservative 11.90 [2.67–21.14] 6 126 Complications (Any Management) Total Complications 31.83 [11.15–52.51] 7 182 Infection 24.91 [8.06–41.77] 7 182 Dexamethasone Therapy Patients Receiving Dexamethasone 61.21 [40.83–81.59] 16 484 Dose per Day (mg/kg/day) 0.92 [0.21–1.63] 3 100 Number of Doses/Day 3.25 [1.78–4.72] 4 66 Duration (days) 4.67 [0.69–8.64] 3 182 Initial Bolus of Dexamethasone Initial Bolus Given 52.54 [28.64–76.44] 14 454 Dose of Initial Bolus (mg/kg) 10.57 [-5.78–26.92] 7 46 Number of Boluses 1.14 [0.86–1.42] 7 46 Clinical Indication for Dexamethasone Edema/Inflammatory Changes 91.06 [80.23–100] 5 394 Neurologic Symptoms of Trauma 93.68 [80.93–100] 4 370 Effect on Patient Course Improvement 55.49 [24.75–86.23] 5 220 Deterioration 29.66 [7.28–52.04] 6 40 Neurological Status Post-Management Improvement 68.94 [57.65–80.23] 14 462 Neutral 15.11 [7.51–22.72] 4 270 Deterioration 23.05 [11.78–34.33] 14 462 Table 3 Subgroup Proportional Analysis of Steroid Use vs. No Steroid Use in Retrospective Studies Category Variable Steroid Use Prevalence (%) [CI] No. of Studies (Steroid) No Steroid Prevalence (%) [CI] No. of Studies (No Steroid) Z-value p-value Age Average Age (years) 8.08 [7.32–8.85] 5 7.31 [6.46–8.17] 5 1.316 0.188 Gender Male 60.00 [17.06–100] 5 90.00 [63.70–100] 4 -1.168 0.243 Female 40.00 [0–82.94] 5 10.00 [0–36.30] 4 -1.168 0.243 Presenting Symptoms Motor Deficits 91.67 [69.55–100] 5 90.00 [63.70–100] 4 0.095 0.924 Altered Mental Status 91.67 [69.55–100] 5 90.00 [63.70–100] 4 0.095 0.924 Physical Exam Comatose 91.67 [69.55–100] 5 90.00 [63.70–100] 4 0.095 0.924 GCS Score 7.58 [5.09–10.07] 4 8.53 [3.75–13.31] 4 -0.347 0.729 Diagnostic Modality CT 96.30 [89.18–100] 2 96.15 [88.76–100] 2 0.028 0.978 Radiologic Findings Fracture 64.08 [45.30–82.86] 2 66.67 [47.81–85.53] 2 -0.190 0.849 Hematoma/Hemorrhage 15.98 [1.62–30.34] 2 16.67 [1.76–31.58] 2 -0.065 0.948 Patient Management Surgical 22.50 [6.36–38.65] 2 16.67 [1.76–31.58] 2 0.521 0.603 Conservative (Dexamethasone) 95.11 [89.64–100] 7 61.74 [24.71–98.77] 6 1.747 0.081 Surgical + Conservative 22.50 [6.36–38.65] 2 3.85 [0–11.24] 2 2.060 0.039 * Complications Any 52.01 [32.44–71.58] 2 16.67 [1.76–31.58] 2 2.815 0.0049 ** Infection 52.01 [32.44–71.58] 2 16.67 [1.76–31.58] 2 2.815 0.0049 ** Dexamethasone Therapy Patients Receiving 95.33 [89.69–100] 6 4.71 [0–10.69] 5 21.603 < 0.001 *** Initial Bolus Given 78.23 [51.35–100] 7 50.00 [0–128.40] 2 0.668 0.504 IV Administration 90.61 [75.47–100] 3 90.00 [71.41–100] 2 0.050 0.960 IM Administration 89.67 [68.92–100] 2 90.00 [63.70–100] 1 -0.019 0.985 Follow-Up Length (months) 7.58 [5.09–10.07] 4 8.53 [3.75–13.31] 4 -0.347 0.729 Neurological Status Improvement 80.58 [68.43–92.72] 5 58.71 [42.46–74.97] 4 2.112 0.0347 * Neutral 8.33 [0–30.45] 1 10.00 [0–36.30] 1 -0.095 0.924 Deterioration 19.42 [7.28–31.57] 5 41.29 [25.03–57.54] 4 -2.112 0.0347 * Fatal Outcome 8.33 [0–30.45] 1 25.00 [0–67.43] 1 -0.683 0.495 Effect on Patient Course Improvement 87.43 [72.30–100] 3 25.00 [0–67.43] 1 2.716 0.0066 ** Deterioration 33.82 [9.56–58.07] 5 10.00 [0–36.30] 1 1.305 0.192 Signs and Symptoms Patients presented with different degrees of visual disturbances (25%), dizziness or vertigo (25%), motor deficits (50%), and altered mental status (75%). Physical examination findings revealed cranial swelling and bruising (50%) with a Glasgow Coma Scale score between 7–10. Management All patients received conservative treatment with dexamethasone. No patients received surgical management. No complications associated with dexamethasone therapy occurred in this patient cohort. The mean follow-up period was 3 months. At final follow-up, 75% of patients experienced neurological improvement and 25% of patients experienced no improvement or deterioration in neurologic outcome (i.e., neutral neurological outcome). No fatal outcomes were reported. Dexamethasone Use All patients received dexamethasone therapy for management of cerebral edema and/or inflammatory changes. The average total dose of dexamethasone prescribed ranged from 8 mg to 80 mg with patients receiving 3 to 4 doses per day (every 6 to 8 hours). Duration of dexamethasone therapy ranged between 5–7 days. Dexamethasone was administered via an intravenous route in 25% of patients, with the route unspecified in the remaining patients. No complications occurred secondary to dexamethasone. All four patients had favorable outcomes following dexamethasone therapy. Prospective and Retrospective Studies: Patient Characteristics Eleven retrospective and/or prospective studies consisting of 493 patients (68.15% male, 31.85% female) were identified for descriptive analysis (Table 2 ). The average age was 7.33 ± 0.66 years. All patients presented with traumatic brain injury. The main diagnostic modality consisted of CT imaging (99.55%). Radiologic findings included fractures (53.40%), cerebral edema and/or swelling (78.45%), and hematoma and/or hemorrhage (19.05%). Signs and Symptoms Patients presented with different degrees of abnormal pupillary response (71.36%), abnormal response to pain (90.12%), motor deficits (90.87%), and altered mental status (99.64%). Physical exam findings revealed coma (99.64%) and cerebral swelling and/or bruising (64.75%) with an average GCS of 8.08. Management Patients received conservative management (82.97%; dexamethasone, sedation, hyperosmolar therapy), surgical management (13.32%), or both (11.90%); categories were not mutually exclusive, so percentages sum to > 100%. Surgical complications occurred in 31.83% of patients, with infection affecting 24.91% of patients. The follow-up period ranged from 6 to 12 months. At final follow-up, 68.94% of patients experienced neurological improvement, 15.11% of patients experienced no change in neurologic status, and 23.05% of patients experienced neurological decline. Dexamethasone Use A descriptive analysis of dexamethasone use was also performed (Table 2 ). 61.21% (N = 287) of patients received dexamethasone therapy with an average dose of 0.92 mg/kg/day for an average of 4.67 days. An initial bolus of dexamethasone was given in 52.54% of patients with an average dose of 10.57 mg given an average of 1.14 times. Clinical indications for dexamethasone therapy consisted of cerebral edema and/or inflammatory changes (N = 368, 91.06%) and neurologic symptoms associated with trauma (N = 355, 93.68%). There were no reported complications associated with dexamethasone therapy; however, of all patients that received dexamethasone therapy, 55.49% (N = 67) of patients had an improvement in clinical course while 23.05% (N = 14) of patients had a deterioration in clinical course. Of the studies that report an improvement in clinical course following dexamethasone therapy, one study mentions that total mortality was significantly reduced in patients who received dexamethasone (N = 66) as compared to patients who did not receive dexamethasone (N = 139) (15.7% vs. 41.7%, p < 0.001). 46 Both groups had similar presentations in terms of type of brain injury, degree of injury, and duration of unconsciousness. The study also reports that patients who received dexamethasone had greater improvements in neurological status (e.g., able to continue their previous schooling, start adequate job training) following treatment (90% vs. 74%). Another study reports that in patients receiving high-dose (1 mg/kg/day) dexamethasone therapy (N = 5), ICP waves and peak ICP were noticeably less (24 torr vs. 58 torr, p < 0.025), and duration of ICU (29.3 ± 17.8 vs. 16.8 ± 8.7 days) and hospital stay (87.0 ± 52.0 vs. 40.0 ± 19.0 days) were shorter as compared to patients who received low-dose (0.25 mg/kg/day) or no dexamethasone therapy (N = 4). 34 Furthermore, it was noted that in patients who received high-dose dexamethasone therapy, neurologic deficits (e.g., spontaneous eye opening, speech) were improved sooner and all patients returned to their premorbid status by six months following injury. Of the patients who received low-dose or no dexamethasone therapy (N = 4), one patient had a fatal outcome, one patient improved by seven months, and the remaining patients still had severe neurological deficits (e.g., aphasia, severely handicapped) by the conclusion of the study. Of the studies that report deterioration in clinical course following dexamethasone therapy, two studies discourage dexamethasone use in pediatric TBI, concluding that dexamethasone suppresses endogenous cortisol production which may increase the risk of bacterial infection without affecting the clinical outcome as compared to patients treated without dexamethasone. 30 , 31 Specifically, the studies had a higher frequency of bacterial pneumonias during the intensive care course in patients treated with dexamethasone as compared to patients who did not receive dexamethasone. One study reports bacterial pneumonia in 7/13 patients treated with dexamethasone versus 2/12 patients who were not treated with dexamethasone. 30 Similarly, the other study reports bacterial pneumonia in 6/12 patients treated with dexamethasone versus 2/12 patients who were not treated with dexamethasone. 31 These studies suggest that endogenous cortisol production is sufficient in management of pediatric TBI. Furthermore, two studies report that dexamethasone therapy amplifies the already heightened post-traumatic catabolic response—measured by total urinary nitrogen loss—in pediatric patients with head injuries, potentially contributing to increased muscle protein breakdown and acquired malnutrition. 32 , 44 One study revealed that patients treated with dexamethasone had a significantly higher daily total urine nitrogen loss compared to patients treated without dexamethasone (256 ± 24 mg/kg/day vs. 172 ± 29 mg/kg/day; p < 0.02). 44 The studies suggest that steroid use mandates aggressive nutritional support in the management of children with head injuries. Additionally, one study reports that dexamethasone administration had no statistically significant effect on ICP or neurological status when high-dose (24 mg/mL) dexamethasone, low-dose (4 mg/mL) dexamethasone, and placebo-treated patients were compared. The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury. 33 A subgroup proportional analysis was completed to compare patients who received dexamethasone with patients who did not (Table 3 ). A p-value of ≤ 0.05 was used to identify statistical significance. From our analysis, we found that patients who suffered from infection following surgery were more likely to receive dexamethasone (52.01% vs. 16.67%, p = 0.0049), although the papers did not define if dexamethasone was given preoperatively, perioperatively, or postoperatively. Interestingly, patients who displayed an improvement in neurologic status following treatment were more likely to have received dexamethasone (80.58% vs. 58.71%, p = 0.0347) while patients who displayed a decline in neurologic status following treatment were less likely to have received dexamethasone (19.42% vs. 41.29%, p = 0.0347). Additionally, in comparing variables among patients with mild/moderate TBI vs. severe TBI (Table 4 ), we found that use of dexamethasone was not significantly different between the two groups (64.94% vs. 50.15%, p = 0.599). Table 4 Mild/Moderate vs Severe TBI in Retrospective Studies Variable Severe TBI Prevalence (%) [CI] No. of Studies (Severe) Mild/Moderate TBI Prevalence (%) [CI] No. of Studies (Mild/Moderate) Z-value p-value Age (years) 7.09 [6.31–7.86] 9 7.92 [6.72–9.11] 4 -1.144 0.253 GCS Score 5.00 [4.44–5.57] 4 11.37 [9.25–13.50] 4 -5.678 < 0.001 *** Conservative Management (Dexamethasone) 79.49 [59.85–99.14] 13 94.50 [86.96–100] 4 -1.398 0.162 Dexamethasone Use 64.94 [41.61–88.28] 12 50.15 [0.26–100] 4 0.526 0.599 Initial Bolus Given 53.36 [26.57–80.15] 12 48.39 [0–134.93] 2 0.108 0.914 Mean Length of Follow-Up (months) 5.00 [4.44–5.57] 4 11.37 [9.25–13.50] 4 -5.678 < 0.001 *** DISCUSSION Our systematic review provides further insight into the clinical landscape surrounding the use of dexamethasone in the management of pediatric neurosurgical trauma. Currently, there are no standard practice guidelines regarding the use of dexamethasone within this patient population, though there is recommendation against its use in severe TBI based on few and small studies. Thus, we performed an extensive systematic review and proportional meta-analysis to assess current recommendations, suggestions, and outcomes in studies utilizing dexamethasone for pediatric neurosurgical trauma. Recommendations surrounding the use of dexamethasone in pediatric neurosurgical trauma management varied among the reviewed studies, with an equal number of articles supporting or opposing dexamethasone therapy. The support for dexamethasone use stemmed from the therapeutic benefit it provided in those studies, such as improvements in functional status, resolution of clinical symptoms, and a reduction in mortality rates. The opposition to dexamethasone use stemmed from its significant side effects or lack of clinical benefit in groups that received dexamethasone as compared to those that did not. Common side effects detailed in the reviewed studies included an increased incidence of bacterial pneumonia and a hypermetabolic state leading to acquired malnutrition and muscle degeneration. 30 , 31 , 32 , 44 Support for Dexamethasone Use Support for dexamethasone use in the reviewed studies centers around the therapeutic benefit it provided in the management of traumatic neurologic injury within the pediatric population. In several studies, dexamethasone was associated with improvement in neurologic status, resolution of clinical symptoms, and reduction in mortality rates. Such studies include reduction in ICP and improvement in neurologic status in patients with severe head injury following trauma. 25 , 34 , 44 , 45 , 42 Notably, only 4 patients were included across the case reports. Among the retrospective series, the studies comparing improvement in clinical course and mortality as a result of steroids did not account for confounding variables. Of the studies reporting reduction in ICP after steroid therapy, there were only 5 patients. A case report by Du Plessis (N = 3), et al. elaborated on how high-dose dexamethasone therapy rapidly resolved uncontrollable ICP refractory to other conservative therapies in three pediatric patients with severe head injuries. 43 The study suggested that high-dose dexamethasone might have played a significant role in the management of pediatric patients with moderate head injuries, focal lesions unresponsive to surgery, and increased ICP. However, the study noted that the administration of pentobarbital therapy prior to dexamethasone might have enhanced the effects of dexamethasone in the patient cohort, although further study was necessary to confirm these findings. Furthermore, a study by Bruce (N = 53), et al. reported that aggressive control of ICP with high-dose dexamethasone reduced the likelihood of secondary injury and diminished mortality and morbidity rates in pediatric patients with severe head injury. 45 Comparably, a study by Gobiet (N = 93), et al described a reduction in mortality in pediatric patients with severe head injuries from 45–16% with the use of high-dose dexamethasone therapy. 25 A similar study by Gobiet, et al. exhibited a significant reduction in mortality (41.7% vs. 15.8%, p < 0.001) (N = 205) and improved return to neurologic baseline in a cohort of severely head-injured pediatric patients who received high-dose dexamethasone as compared to a cohort who did not receive dexamethasone therapy. 46 The study attributed the improved clinical outcomes to dexamethasone’s ability to considerably reduce the number of abnormal rises in ICP and incidence of secondary complications. However, the study noted that direct measurement of ICP was imperative as abnormal rises in ICP might still occur even when high-dose dexamethasone was administered. Finally, a study by James, (N = 9) et al. examined the impact of high-dose dexamethasone, low-dose dexamethasone, and no dexamethasone on the clinical outcomes of pediatric patients with severe closed head injury. 34 The study found that patients who received high-dose dexamethasone had a greater reduction in ICP, shorter ICU and hospital stay, faster improvements in neurologic deficits, greater returns to neurologic baseline, and significantly better quality of survival, without significant complications, as compared to the low-dose dexamethasone and no dexamethasone cohorts. The study accredited these outcomes to dexamethasone’s anti-edematous properties in addition to its capacity to improve cell metabolism, strengthen cell membrane and blood-brain-barrier integrity, encourage intracranial compliance, and stabilize cerebral blood flow. None of the patients within the aforementioned studies experienced significant complications secondary to dexamethasone therapy. Opposition to Dexamethasone Use Opposition to dexamethasone use in the reviewed studies stems from the complications and side effects associated with dexamethasone therapy, in addition to the expressed lack of clinical benefit in cohorts treated with dexamethasone as compared to cohorts treated without dexamethasone. Common side effects included gastrointestinal bleeding, hyperglycemia, hypertension, infections, prolongation of the catabolic phase, sodium retention, and potassium excretion, which might contribute to avoidable morbidity and mortality. 36 , 37 , 38 , 39 , 40 A study by Fanconi, et al, reviewed the clinical effectiveness of high-dose dexamethasone therapy in pediatric patients with severe head injury. 30 The results of the study ultimately discouraged the use of dexamethasone in pediatric neurosurgical trauma on the premise that dexamethasone suppresses endogenous cortisol production, contributing to an increased risk of bacterial infections. The study had an incidence of bacterial pneumonia in 53.8% of patients within the dexamethasone-treated group versus 16.7% of patients within the non-dexamethasone-treated group. Furthermore, the study determined that there was no statistically significant difference in the clinical outcomes and laboratory data between patients treated with high-dose dexamethasone in relation to those treated without dexamethasone. The study argued that endogenous steroid production was sufficient in eliciting maximum glucocorticoid effects, contributing to membrane stabilization and prevention of brain edema, and that exogenous steroids did not display any additional therapeutic benefit. A study by Kloti, et al, shared this sentiment, endorsing that endogenous steroid production alone was sufficient in the management of severe pediatric head injury and that routine administration of dexamethasone should be reevaluated. 31 A study by Ford, et al found that dexamethasone therapy increased the existing accelerated post-traumatic catabolic response in pediatric patients with head injuries, contributing to elevated muscle protein breakdown and acquired malnutrition. 44 The article suggested the addition of aggressive nutritional support in pediatric patients with head injuries managed with steroids to counterbalance the hypermetabolic state and offset secondary complications. Nevertheless, the study recommended the removal of dexamethasone from the management of pediatric patients suffering head injuries due to these findings. A study by Andrassy, et al had similar findings and further discussed how malnutrition secondary to the systemic hypermetabolism following traumatic neurologic injury can increase the likelihood of morbidity and mortality. 32 An article by Cooper et al, found no significant effect on ICP patterns, neurological status, and morbidity or mortality when low-dose or high-dose dexamethasone was administered to adult and pediatric patients with severe head injury in comparison to placebo-treated patients. 33 Dexamethasone Use in Severe TBI vs. Mild/Moderate TBI Nine of the reviewed studies discussed dexamethasone use in pediatric patients with severe TBI 30 , 31 , 33 , 34 , 45 , 46 , 49 , 50 , 51 . Of the nine, both support for and opposition to dexamethasone use were of equal amounts. Support for dexamethasone use in severe TBI were based on clinical results suggesting improved clinical outcomes following dexamethasone administration. Specifically, patients with severe TBI that received dexamethasone therapy exhibited reduced mortality rates, greater improvements in neurological status, decreased ICP status, and shorter ICU and hospital stays. 34 , 45 , 46 Opposition to dexamethasone use in severe TBI centered around clinical results suggesting that dexamethasone has no effect on clinical outcomes and may increase risk of infection. 30 , 31 , 33 These studies suggested that endogenous cortisol production was sufficient for management of severe TBI in pediatric patients. Three of the reviewed studies discussed dexamethasone use in pediatric patients with mild or moderate TBI. 32 , 43 , 44 Of the three, one study expressed strong support for dexamethasone use following results demonstrating decreased ICP status and improved neurologic status in pediatric patients that received dexamethasone therapy following mild/moderate TBI. 43 The results of the other two studies suggested that dexamethasone therapy increased the existing accelerated post-traumatic catabolic response in pediatric patients with mild/moderate TBI, contributing to elevated muscle protein breakdown and acquired malnutrition. 32 , 44 Current guidelines on the use of dexamethasone in adult traumatic brain injury (TBI) The Corticosteroid Randomization After Significant Head Injury (CRASH) trial was a placebo-controlled trial of 10,008 adults with TBI that found that corticosteroids should not be routinely used to manage TBI in adults. 6 The results of the trial revealed that patients who received corticosteroids (methylprednisolone) had a higher risk of severe disability or death than those who received a placebo. The findings of the study concluded that corticosteroids should not be routinely used to treat TBI. Similarly, the Brain Trauma Foundation Guidelines for the Management of Severe TBI, 4th Edition also recommends against the use of corticosteroids to treat TBI in adults. 46 Current guidelines on the use of dexamethasone in pediatric traumatic brain injury (TBI) According to the most recent edition of the Brain Trauma Foundation Guidelines for the management of pediatric severe TBI, the use of steroids was not suggested to improve outcome or reduce ICP. 51 Only two small and outdated studies—both included in our meta-analysis—were used to support the recommendation. These studies, conducted by Kloti and Fanconi and published in 1987 and 1988, included 24 and 25 patients, respectively. 30 , 31 Nevertheless, although dexamethasone has been found to offer significant clinical benefit in the management of pediatric neurosurgical cases, mainly tumors, the adverse effects related to dexamethasone administration in this population must also be considered. The main reported adverse effects of dexamethasone administration have included infectious, gastrointestinal, psychological, and growth abnormalities. 28 , These side effects are dose-dependent with a direct correlation between dexamethasone treatment length and adverse effect incidence. 27 Thus, dexamethasone administration requires careful consideration regarding dosing and duration to ensure its safety and efficacy in the pediatric population. Limitations This systematic review and proportional meta-analysis was limited by the number and type of studies we were able to include. We identified only 13 studies, of which 2 were case reports and 11 were retrospective/prospective series. Heterogeneity across study designs, patient populations, dosing regimens, comparators, and outcome definitions was high; most included studies were small, single-center, and several were conducted decades ago, which limits generalizability and increases the potential for bias. As a result, pooled estimates should be interpreted cautiously. We were unable to evaluate many clinically relevant subgroups, and findings may be confounded by indication and center-level practice patterns. Future prospective, adequately powered studies using standardized definitions and outcomes are needed. CONCLUSION Dexamethasone is a commonly used glucocorticoid with many roles in a neurosurgical setting. From the studies included in this systematic review of dexamethasone use in pediatric trauma, most studies reported limited or no benefit and increased complications such as gastrointestinal bleeding, hyperglycemia, hypertension and infections. A few other studies, published in the late 1970s and 1980s, reported its benefits such as improvement in clinical symptoms, reduction in ICP and reduction in mortality rates. In pooled proportional analyses, neurological improvement was more frequent among dexamethasone-treated patients, but infections were also more common, underscoring equipoise. At this time, however, we are unable to make a recommendation for or against its use due to the limited number and poor quality of studies regarding dexamethasone use in the management of TBI. Thus, more research is required to fully understand the effects of dexamethasone in the setting of pediatric neurosurgical trauma and create guidelines for its use. Declarations Competing Interests and Funding No funding was provided, and the authors have no competing interests as defined by Springer. References Alali AS, Gomez D, Sathya C, Burd RS, Mainprize TG, Moulton R et al (2015) Intracranial pressure monitoring among children with severe traumatic brain injury. J Neurosurg Pediatr 16:523–532. https://doi.org/10.3171/2015.3.PEDS14543 Alkhoury F, Kyriakides TC (2014) Intracranial pressure monitoring in children with severe traumatic brain injury: national trauma data bank-based review of outcomes. JAMA Surg 149:544–548. https://doi.org/10.1001/jamasurg.2013.4525 Araki T, Yokota H, Morita A (2017) Pediatric traumatic brain injury: characteristic features, diagnosis, and management. Neurol Med Chir (Tokyo) 57:82–93. https://doi.org/10.2176/nmc.ra.2016-0191 Brady KM, Shaffner DH, Lee JK, Easley RB, Smielewski P, Czosnyka M et al (2009) Continuous monitoring of cerebrovascular pressure reactivity after traumatic brain injury in children. 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In: Pappius HM, Reulen HJ (eds) Dynamics of Brain Edema. Springer, Berlin/Heidelberg/New York, pp 337–343 Chumbala Na Ayudhaya A, Morrison SR, Kaliaperumal C et al (2022) A 10-year retrospective observational study on the utility and prescription standards of dexamethasone in pediatric neuro-oncosurgery in a tertiary care center. Childs Nerv Syst 38:1707–1715. https://doi.org/10.1007/s00381-022-05569-6 Stuart FA, Segal TY, Keady S (2005) Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child 90:500–506. https://doi.org/10.1136/adc.2003.041541 Chrysis D, Ritzen EM, Sävendahl L (2003) Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes. J Endocrinol 176:331–337. https://doi.org/10.1677/joe.0.1760331 Fanconi S, Klöti J, Meuli M, Zaugg H, Zachmann M (1988) Dexamethasone therapy and endogenous cortisol production in severe pediatric head injury. Intensive Care Med 14:163–166. https://doi.org/10.1007/BF00257471 Klöti J, Fanconi S, Zachmann M, Zaugg H (1987) Dexamethasone therapy and cortisol excretion in severe pediatric head injury. Childs Nerv Syst 3:103–105. https://doi.org/10.1007/BF00271134 Andrassy RJ, Dubois T (1985) Modified injury severity scale and concurrent steroid therapy: independent correlates of negative nitrogen balance in pediatric trauma. J Pediatr Surg 20:799–802. https://doi.org/10.1016/S0022-3468(85)80046-4 Cooper PR, Moody S, Clark WK et al (1979) Dexamethasone and severe head injury: a prospective double-blind study. J Neurosurg 51:307–316. https://doi.org/10.3171/jns.1979.51.3.0307 James HE, Madauss WC, Tibbs PA, McCloskey JJ, Bean JR (1979) The effect of high dose dexamethasone in children with severe closed head injury: a preliminary report. 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Ann Surg 202:248–252. https://doi.org/10.1097/00000658-198508000-00008 Clifton GL, Robertson CS, Grossman RG, Hodge S, Foltz R, Garza C (1984) The metabolic response to severe head injury. J Neurosurg 60:687–696. https://doi.org/10.3171/jns.1984.60.4.0687 Milanovic F, Abramovic D, Ducic S et al (2021) Brachial plexopathy as a consequence of nerve root swelling after shoulder trauma in a patient following an acute seizure. Turk J Pediatr 63:161–166. https://doi.org/10.24953/turkjped.2021.01.020 de Melo PM, Kadri PA, de Oliveira JG, Suriano IC, Cavalheiro S, Braga FM (2003) Cervical epidural haematoma with clivus fracture: case report. Arq Neuropsiquiatr 61:499–502. https://doi.org/10.1590/S0004-282X2003000300034 Du Plessis JJ (1992) High-dose dexamethasone therapy in head injury: a patient group that may benefit from therapy. Br J Neurosurg 6:145–147. https://doi.org/10.3109/02688699209002917 Ford EG, Jennings LM, Andrassy RJ (1987) Steroid administration potentiates urinary nitrogen losses in head-injured children. J Trauma 27:1074–1077. https://doi.org/10.1097/00005373-198709000-00020 Bruce DA, Schut L, Bruno LA, Wood JH, Sutton LN (1978) Outcome following severe head injuries in children. J Neurosurg 48:679–688. https://doi.org/10.3171/jns.1978.48.5.0679 Gobiet W (1977) Advances in management of severe head injuries in childhood. Acta Neurochir (Wien) 39:201–210. https://doi.org/10.1007/BF01406730 Celmer P (2023) Guidelines for the management of severe TBI, 4th edition. Brain Trauma Foundation. Accessed 20 Aug 2025 Pfenninger J, Kaiser G, Lütschg J, Sutter M (1983) Treatment and outcome of the severely head injured child. Intensive Care Med 9:13–16. https://doi.org/10.1007/BF01693699 Mayer T, Walker ML (1982) Emergency intracranial pressure monitoring in pediatrics: management of the acute coma of brain insult. Clin Pediatr (Phila) 21:391–396. https://doi.org/10.1177/000992288202100701 Barzilay Z, Augarten A, Sagy M, Shahar E, Yahav Y, Boichis H (1988) Variables affecting outcome from severe brain injury in children. Intensive Care Med 14:417–421. https://doi.org/10.1007/BF00262899 Farrell D, Bendo AA (2018) Perioperative management of severe traumatic brain injury: what is new? Curr Anesthesiol Rep 8:279–289. https://doi.org/10.1007/s40140-018-02861 Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR et al (2019) Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guidelines. Pediatr Crit Care Med 20(Suppl 1):S1–S82. https://doi.org/10.1097/PCC.0000000000001735 Additional Declarations No competing interests reported. Supplementary Files SupplementalTables.docx Supplemental Table 1. Demographics, trauma characteristics, dexamethasone strategies, and outcomes of the case reports Supplemental Table 2. Demographics, trauma characteristics, dexamethasone strategies, and outcomes of the retrospective studies Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7467090","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":509819585,"identity":"a0dfa7ab-c9b9-40c1-80a7-7f7de9dfdbe6","order_by":0,"name":"Ezinwa 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07:12:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2156708,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7467090/v1/9ead5e60-fca5-42cc-a453-a4dc773afab6.pdf"},{"id":90885438,"identity":"c670236e-fb60-42e9-98e3-ef26b18a430a","added_by":"auto","created_at":"2025-09-09 10:06:59","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19987,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Table 1. \u003c/strong\u003eDemographics, trauma characteristics, dexamethasone strategies, and outcomes of the case reports\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplemental Table 2. \u003c/strong\u003eDemographics, trauma characteristics, dexamethasone strategies, and outcomes of the retrospective studies\u003c/p\u003e","description":"","filename":"SupplementalTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7467090/v1/1eca7be5eb4702198d8c67c2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dexamethasone Use in Pediatric Neurosurgical Trauma: A Systematic Review and Proportional Meta-Analysis of the Current Literature","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTraumatic brain injury (TBI) is a leading cause of injury in children with a report detailing 475,000 cases in the United States each year.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eFollowing an initial insult, TBI patients may undergo an expansion of intracranial volume leading to secondary injury. According to the Monro-Kellie hypothesis, intracranial space is composed of brain tissue, cerebrospinal fluid (CSF), and blood. Expansion of one of these components, or introduction of a new material, will result in an increase in the intracranial pressure (ICP) and/or a reflexive decrease in the volume of one of the other compartments. One of the goals of TBI management is to maintain homeostasis of all three intracranial components to protect cerebral blood flow and to preserve cerebral perfusion.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNeurosurgical trauma in children presents a set of challenges unique to the pediatric population. Because the skull is developing, pediatric patients have greater cranial plasticity/deformability, altering the biomechanical response to impact.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Despite this, developing pediatric brains are not fully myelinated, increasing susceptibility to traumatic forces in the unmyelinated regions of the brain.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Although there is significant variation between institutions in TBI treatment, management of pediatric TBI, after careful attention to airway, breathing, and circulation (ABCs), commonly begins with ICP monitoring.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Recent studies have suggested that ICP monitoring in severe TBI patients reduces deaths and improves survival.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The goal of ICP monitoring is to guide physicians in maintaining cerebral perfusion pressure (CPP). This is accomplished by reducing intracranial volume which has been shown to be essential for positive outcomes in children.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e To maintain CPP within normal limits, medical and surgical management may include sedatives and analgesics for anesthesia, hyperosmolar therapy, CSF drainage, hyperventilation, barbiturates, craniotomy for evacuation of hematomas, decompressive craniectomy, and corticosteroids.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIndications for corticosteroids in neurosurgical trauma remain a source of controversy with varying reports as to their efficacy in the treatment of spinal, peripheral nerve, and cranial trauma.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Dexamethasone, a commonly used corticosteroid, is thought by some to mitigate deleterious effects of secondary injury following trauma by reducing inflammation around peripheral nerves and the brain therefore decreasing ICP in TBI.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Corticosteroids are hypothesized to restore vascular permeability, reduce edema/CSF production, and diminish free-radical injury. However, a large randomized trial in adults found no significant improvement in morbidity and mortality when patients were given corticosteroids following a TBI.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Following this study, Clinical Practice Guidelines for adult TBI recommended against the use of high-dose dexamethasone in adult TBI.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e Despite significant study in adults, there is little evidence as to the efficacy of dexamethasone in the setting of pediatric neurosurgical trauma. According to the latest edition of the Brain Trauma Foundation Guidelines for the management of pediatric severe TBI, there was a weak recommendation (level III) stating that the use of steroids was not suggested to improve outcome or reduce ICP. Only two very old and small studies were included to support the recommendation.\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e Here we provide a review of the literature published on the use of dexamethasone in pediatric neurosurgical trauma.\u003c/p\u003e\u003cp\u003eThe objectives of this review are to 1) provide the first systematic review and proportional meta-analysis of current literature on the use of dexamethasone in the management of pediatric TBI, 2) highlight patient characteristics, risk factors, and dexamethasone dosing in pediatric neurosurgical TBI, and 3) provide guidance on the use of dexamethasone in pediatric TBI.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eContributing Authors\u003c/h2\u003e\u003cp\u003eSeven authors contributed to this project: Ezinwa Kalunta-Crumpton (Corresponding Author, The University of Texas Southwestern Medical Center, Dallas, United States; [email protected]) performed data collection, conducted article review, wrote the main manuscript text, and prepared all tables and figures. Sanjay Neerukonda (The University of Texas Health Science Center at Houston, Houston, United States; [email protected]) assisted with data collection and edited abstract. Parker Smith (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected]) assisted with data collection and wrote the introduction. Peace Odiase (Meharry Medical College, Nashville, United States; [email protected]) performed all statistical analyses of the collected data. Abigail Jenkins (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected]) supported manuscript completion by coordinating assignments and ensuring deadlines were met. Umaru Barrie (New York University Langone Medical Center, New York, United States; [email protected]) conceived the manuscript topic and organized the research team. Bruno Braga (The University of Texas Southwestern Medical Center, Dallas, United States; [email protected]) reviewed and edited the entire manuscript prior to submission.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eWe conducted our literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e We queried the online database PubMed on December 1st, 2023. The key search terms were \u0026ldquo;dexamethasone AND pediatric AND trauma\u0026rdquo;. Other terms included \u0026ldquo;neurosurgery\u0026rdquo; OR \u0026ldquo;children\u0026rdquo; OR \u0026ldquo;management\u0026rdquo; OR \u0026ldquo;outcomes\u0026rdquo;. Exclusion criteria were as follows: adult (\u0026gt;\u0026thinsp;18 years old) patient population, articles not written in English, literature reviews, correspondences, commentaries, book chapters, animal studies and opinion pieces. Other exclusion criteria included incomplete reporting of primary outcomes, surgical management not specified, studies with overlapping study populations, and the following etiologies: spinal cord injury, peripheral neuropathies, infection, tumor; only TBI was included.\u003c/p\u003e\u003cp\u003eThe objective of the study was to discuss, analyze, and examine all original articles exploring recommendations and outcomes in pediatric patients with neurosurgical trauma in which dexamethasone was used as a part of the medical management.\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eThree authors (E.K.C [Corresponding Author], S.V.N, P.S.) independently performed the data extraction according to the search strategy. Discrepancies in inclusion criteria or collected data were evaluated by the authors and discussed to find a resolution. Identified articles were first screened by title, followed by abstracts and full texts to determine inclusion. An in-depth full-text review of all case studies and retrospective reviews was performed for the extraction of relevant data. Relevant data included research aim, population demographic, clinical characteristics, underlying conditions and predispositions, management, outcomes, and recommendations. Our data extraction and analysis incorporated demographic of patient population, patient presentation, underlying conditions or familial history, type of trauma, imaging modality and findings, dexamethasone dosing and duration, conservative or surgical management, other steroids used, complications related to dexamethasone, neurological outcome, and follow-up duration.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eWe evaluated the distribution of our population characteristics with descriptive statistics. We assessed the occurrence of the objective based on the reported data. We predetermined the following characteristics of interest: average age, ratio of female to male patients, presenting signs and symptoms, physical exam findings, diagnostic modality, trauma type, dexamethasone dose and duration, form of intervention, and patient outcomes.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProportional Meta-Analysis\u003c/h3\u003e\n\u003cp\u003eAnalyses were performed in R (version 4.3.x) using RStudio with the metafor, meta, and metadat packages. Given the expected high variability among the included studies, a random-effects model (REM) was employed for data aggregation. Heterogeneity across studies was assessed using Cochran\u0026rsquo;s Q statistic, and the I\u0026sup2; test was applied to quantify the extent of heterogeneity. Additionally, 95% prediction intervals were calculated to estimate the range within which the true effect size is likely to fall in future studies, accounting for between-study variability. Forest plots were used to visually represent proportions. Subgroup analyses were conducted to examine how different population categories might impact the pooled proportions. Summary estimates between two independent subgroup meta-analyses were compared using a Wald-type test to determine significant differences. For categorical data, frequencies and percentages were calculated based on individual studies, while continuous data were summarized by calculating means and standard deviations from pooled data. Descriptive statistics were reported based on the available data from each study. Transparency was ensured by clearly stating the number of studies from which data were successfully extracted and detailing the patient count for each variable of interest relative to the total patient population within each study. A narrative summary was provided to report the challenges encountered and the proposed solutions identified in the literature. Of note, we excluded categories that were not mentioned in more than one paper (any categories where N\u0026thinsp;=\u0026thinsp;1; see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eElectronic Search Yield\u003c/h2\u003e\n\u003cp\u003eFollowing the employment of PRISMA guidelines, our initial literature search produced 597 publications \u003cstrong\u003e(\u003c/strong\u003eFig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Publications were excluded based on the criteria (n\u0026thinsp;=\u0026thinsp;556), leaving 41 articles for preliminary review. An additional 28 articles were excluded following full-text review, producing a final total of 13 articles. Of the 13 articles, 2 were case reports (\u003cstrong\u003eSupplemental Table\u0026nbsp;1\u003c/strong\u003e) and 11 were retrospective reviews (\u003cstrong\u003eSupplemental Table\u0026nbsp;2\u003c/strong\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eCase Reports:\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003ePatient Characteristics\u003c/h2\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e outlines patient demographics, presentation, management, and clinical outcome for all case reports included in the systematic review. Four patients (3 males, 1 female) were identified for analysis, with a mean age of 13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65 years. All patients presented with traumatic brain injury. Diagnostic modalities varied between radiographs (25%), CT (100%), and MRI (25%). Radiologic findings included fractures and/or dislocations (25%), cerebral edema and/or swelling (50%), and hematoma and/or hemorrhage (50%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePatient demographics, presentation, management, and outcomes for case reports\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCategory\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDetails\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Demographics\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge: 13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65 years\u003c/p\u003e\n\u003cp\u003eSex: Male 3 (75%), Female 1 (25%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePresenting Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Visual disturbances: 1 (25%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Dizziness: 1 (25%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Motor deficits: 2 (50%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Altered mental status: 3 (75%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eManagement\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical: 0 (0%)\u003c/p\u003e\n\u003cp\u003eConservative: 4 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDexamethasone Therapy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Patients receiving: 4 (100%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Dose: 8\u0026ndash;80 mg, 3\u0026ndash;4 times/day\u003c/p\u003e\n\u003cp\u003e\u0026bull; Duration: 5\u0026ndash;7 days\u003c/p\u003e\n\u003cp\u003e\u0026bull; Route: IV 1 (25%), IM 0 (0%), PO 0 (0%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Indication: Edema/inflammatory changes 4 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePhysical Examination\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCS Score: 7\u0026ndash;10\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eImaging Modality\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCT: 4 (100%)\u003c/p\u003e\n\u003cp\u003eX-Ray: 1 (25%)\u003c/p\u003e\n\u003cp\u003eMRI: 1 (25%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRadiologic Findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Edema/Swelling: 2 (50%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Hematoma/Hemorrhage: 2 (50%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Fracture: 1 (25%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-Up / Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFollow-Up: 3 months\u003c/p\u003e\n\u003cp\u003eNeurologic Outcome: Improvement 3 (75%), Neutral 1 (25%), Deterioration 0 (0%)\u003c/p\u003e\n\u003cp\u003ePatient Course: Improved 4 (100%), Worsened 0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComplications\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eOverall Descriptives for Retrospective Studies\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCategory\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePrevalence (%) [95% CI]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN (Studies)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal Patients\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAverage Age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.33 [6.67\u0026ndash;7.99]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e278\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e68.15 [45.91\u0026ndash;90.39]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e89\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31.85 [9.61\u0026ndash;54.09]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e89\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePresenting Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVisual Disturbances\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e71.36 [33.09\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e338\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSensory Deficits\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.12 [71.40\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e338\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMotor Deficits\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.87 [79.49\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e347\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltered Mental Status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e99.64 [99.02\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e347\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePhysical Exam Findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComatose\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e99.64 [99.02\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e347\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCS Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.08 [5.55\u0026ndash;10.62]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e89\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Modality\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e99.55 [98.93\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e443\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRadiologic Findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFracture\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e53.40 [38.40\u0026ndash;68.40]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e102\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEdema/Swelling\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e78.45 [48.42\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e338\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHematoma/Hemorrhage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19.05 [11.10\u0026ndash;27.00]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e331\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Management\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical Management\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13.32 [7.65\u0026ndash;19.00]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e126\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConservative Management (Dexamethasone)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e82.97 [68.79\u0026ndash;97.14]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e288\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCombined Surgical \u0026amp; Conservative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.90 [2.67\u0026ndash;21.14]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e126\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComplications (Any Management)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Complications\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31.83 [11.15\u0026ndash;52.51]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e182\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInfection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24.91 [8.06\u0026ndash;41.77]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e182\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDexamethasone Therapy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePatients Receiving Dexamethasone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e61.21 [40.83\u0026ndash;81.59]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e484\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDose per Day (mg/kg/day)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.92 [0.21\u0026ndash;1.63]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e100\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of Doses/Day\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.25 [1.78\u0026ndash;4.72]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e66\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuration (days)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.67 [0.69\u0026ndash;8.64]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e182\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eInitial Bolus of Dexamethasone\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInitial Bolus Given\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e52.54 [28.64\u0026ndash;76.44]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e454\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDose of Initial Bolus (mg/kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.57 [-5.78\u0026ndash;26.92]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of Boluses\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.14 [0.86\u0026ndash;1.42]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Indication for Dexamethasone\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEdema/Inflammatory Changes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.06 [80.23\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e394\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeurologic Symptoms of Trauma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e93.68 [80.93\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e370\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eEffect on Patient Course\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImprovement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e55.49 [24.75\u0026ndash;86.23]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e220\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeterioration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29.66 [7.28\u0026ndash;52.04]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNeurological Status Post-Management\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImprovement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e68.94 [57.65\u0026ndash;80.23]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e462\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeutral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e15.11 [7.51\u0026ndash;22.72]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e270\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeterioration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23.05 [11.78\u0026ndash;34.33]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e462\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSubgroup Proportional Analysis of Steroid Use vs. No Steroid Use in Retrospective Studies\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCategory\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSteroid Use Prevalence (%) [CI]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of Studies (Steroid)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo Steroid Prevalence (%) [CI]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of Studies (No Steroid)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eZ-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAverage Age (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.08 [7.32\u0026ndash;8.85]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.31 [6.46\u0026ndash;8.17]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.316\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.188\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e60.00 [17.06\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [63.70\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-1.168\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.243\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40.00 [0\u0026ndash;82.94]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.00 [0\u0026ndash;36.30]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-1.168\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.243\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePresenting Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMotor Deficits\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.67 [69.55\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [63.70\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.095\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.924\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltered Mental Status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.67 [69.55\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [63.70\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.095\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.924\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePhysical Exam\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComatose\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.67 [69.55\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [63.70\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.095\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.924\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCS Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.58 [5.09\u0026ndash;10.07]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.53 [3.75\u0026ndash;13.31]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.347\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.729\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Modality\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e96.30 [89.18\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e96.15 [88.76\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.028\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.978\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRadiologic Findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFracture\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e64.08 [45.30\u0026ndash;82.86]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e66.67 [47.81\u0026ndash;85.53]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.190\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.849\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHematoma/Hemorrhage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e15.98 [1.62\u0026ndash;30.34]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.67 [1.76\u0026ndash;31.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.065\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.948\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Management\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22.50 [6.36\u0026ndash;38.65]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.67 [1.76\u0026ndash;31.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.521\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.603\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConservative (Dexamethasone)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e95.11 [89.64\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e61.74 [24.71\u0026ndash;98.77]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.747\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.081\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical\u0026thinsp;+\u0026thinsp;Conservative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22.50 [6.36\u0026ndash;38.65]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.85 [0\u0026ndash;11.24]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.060\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.039 *\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComplications\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAny\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e52.01 [32.44\u0026ndash;71.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.67 [1.76\u0026ndash;31.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.815\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0049 **\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInfection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e52.01 [32.44\u0026ndash;71.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.67 [1.76\u0026ndash;31.58]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.815\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0049 **\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDexamethasone Therapy\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePatients Receiving\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e95.33 [89.69\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.71 [0\u0026ndash;10.69]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.603\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001 ***\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInitial Bolus Given\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e78.23 [51.35\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e50.00 [0\u0026ndash;128.40]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.668\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.504\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIV Administration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.61 [75.47\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [71.41\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.050\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.960\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIM Administration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e89.67 [68.92\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00 [63.70\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.985\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-Up\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLength (months)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.58 [5.09\u0026ndash;10.07]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.53 [3.75\u0026ndash;13.31]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.347\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.729\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNeurological Status\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImprovement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e80.58 [68.43\u0026ndash;92.72]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e58.71 [42.46\u0026ndash;74.97]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.112\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0347 *\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeutral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.33 [0\u0026ndash;30.45]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.00 [0\u0026ndash;36.30]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.095\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.924\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeterioration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19.42 [7.28\u0026ndash;31.57]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.29 [25.03\u0026ndash;57.54]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-2.112\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0347 *\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFatal Outcome\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.33 [0\u0026ndash;30.45]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25.00 [0\u0026ndash;67.43]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.683\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.495\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eEffect on Patient Course\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImprovement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e87.43 [72.30\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25.00 [0\u0026ndash;67.43]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.716\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0066 **\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeterioration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33.82 [9.56\u0026ndash;58.07]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.00 [0\u0026ndash;36.30]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.305\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.192\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eSigns and Symptoms\u003c/h2\u003e\n\u003cp\u003ePatients presented with different degrees of visual disturbances (25%), dizziness or vertigo (25%), motor deficits (50%), and altered mental status (75%). Physical examination findings revealed cranial swelling and bruising (50%) with a Glasgow Coma Scale score between 7\u0026ndash;10.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003eManagement\u003c/h2\u003e\n\u003cp\u003eAll patients received conservative treatment with dexamethasone. No patients received surgical management. No complications associated with dexamethasone therapy occurred in this patient cohort. The mean follow-up period was 3 months. At final follow-up, 75% of patients experienced neurological improvement and 25% of patients experienced no improvement or deterioration in neurologic outcome (i.e., neutral neurological outcome). No fatal outcomes were reported.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003ch2\u003eDexamethasone Use\u003c/h2\u003e\n\u003cp\u003eAll patients received dexamethasone therapy for management of cerebral edema and/or inflammatory changes. The average total dose of dexamethasone prescribed ranged from 8 mg to 80 mg with patients receiving 3 to 4 doses per day (every 6 to 8 hours). Duration of dexamethasone therapy ranged between 5\u0026ndash;7 days. Dexamethasone was administered via an intravenous route in 25% of patients, with the route unspecified in the remaining patients. No complications occurred secondary to dexamethasone. All four patients had favorable outcomes following dexamethasone therapy.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n\u003ch2\u003eProspective and Retrospective Studies:\u003c/h2\u003e\n\u003cdiv id=\"Sec16\" class=\"Section3\"\u003e\n\u003ch2\u003ePatient Characteristics\u003c/h2\u003e\n\u003cp\u003eEleven retrospective and/or prospective studies consisting of 493 patients (68.15% male, 31.85% female) were identified for descriptive analysis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The average age was 7.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 years. All patients presented with traumatic brain injury. The main diagnostic modality consisted of CT imaging (99.55%). Radiologic findings included fractures (53.40%), cerebral edema and/or swelling (78.45%), and hematoma and/or hemorrhage (19.05%).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n\u003ch2\u003eSigns and Symptoms\u003c/h2\u003e\n\u003cp\u003ePatients presented with different degrees of abnormal pupillary response (71.36%), abnormal response to pain (90.12%), motor deficits (90.87%), and altered mental status (99.64%). Physical exam findings revealed coma (99.64%) and cerebral swelling and/or bruising (64.75%) with an average GCS of 8.08.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n\u003ch2\u003eManagement\u003c/h2\u003e\n\u003cp\u003ePatients received conservative management (82.97%; dexamethasone, sedation, hyperosmolar therapy), surgical management (13.32%), or both (11.90%); categories were not mutually exclusive, so percentages sum to \u0026gt;\u0026thinsp;100%. Surgical complications occurred in 31.83% of patients, with infection affecting 24.91% of patients. The follow-up period ranged from 6 to 12 months. At final follow-up, 68.94% of patients experienced neurological improvement, 15.11% of patients experienced no change in neurologic status, and 23.05% of patients experienced neurological decline.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n\u003ch2\u003eDexamethasone Use\u003c/h2\u003e\n\u003cp\u003eA descriptive analysis of dexamethasone use was also performed (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 61.21% (N\u0026thinsp;=\u0026thinsp;287) of patients received dexamethasone therapy with an average dose of 0.92 mg/kg/day for an average of 4.67 days. An initial bolus of dexamethasone was given in 52.54% of patients with an average dose of 10.57 mg given an average of 1.14 times. Clinical indications for dexamethasone therapy consisted of cerebral edema and/or inflammatory changes (N\u0026thinsp;=\u0026thinsp;368, 91.06%) and neurologic symptoms associated with trauma (N\u0026thinsp;=\u0026thinsp;355, 93.68%). There were no reported complications associated with dexamethasone therapy; however, of all patients that received dexamethasone therapy, 55.49% (N\u0026thinsp;=\u0026thinsp;67) of patients had an improvement in clinical course while 23.05% (N\u0026thinsp;=\u0026thinsp;14) of patients had a deterioration in clinical course.\u003c/p\u003e\n\u003cp\u003eOf the studies that report an improvement in clinical course following dexamethasone therapy, one study mentions that total mortality was significantly reduced in patients who received dexamethasone (N\u0026thinsp;=\u0026thinsp;66) as compared to patients who did not receive dexamethasone (N\u0026thinsp;=\u0026thinsp;139) (15.7% vs. 41.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003csup\u003e46\u003c/sup\u003e Both groups had similar presentations in terms of type of brain injury, degree of injury, and duration of unconsciousness. The study also reports that patients who received dexamethasone had greater improvements in neurological status (e.g., able to continue their previous schooling, start adequate job training) following treatment (90% vs. 74%). Another study reports that in patients receiving high-dose (1 mg/kg/day) dexamethasone therapy (N\u0026thinsp;=\u0026thinsp;5), ICP waves and peak ICP were noticeably less (24 torr vs. 58 torr, p\u0026thinsp;\u0026lt;\u0026thinsp;0.025), and duration of ICU (29.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 vs. 16.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 days) and hospital stay (87.0\u0026thinsp;\u0026plusmn;\u0026thinsp;52.0 vs. 40.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0 days) were shorter as compared to patients who received low-dose (0.25 mg/kg/day) or no dexamethasone therapy (N\u0026thinsp;=\u0026thinsp;4).\u003csup\u003e34\u003c/sup\u003e Furthermore, it was noted that in patients who received high-dose dexamethasone therapy, neurologic deficits (e.g., spontaneous eye opening, speech) were improved sooner and all patients returned to their premorbid status by six months following injury. Of the patients who received low-dose or no dexamethasone therapy (N\u0026thinsp;=\u0026thinsp;4), one patient had a fatal outcome, one patient improved by seven months, and the remaining patients still had severe neurological deficits (e.g., aphasia, severely handicapped) by the conclusion of the study.\u003c/p\u003e\n\u003cp\u003eOf the studies that report deterioration in clinical course following dexamethasone therapy, two studies discourage dexamethasone use in pediatric TBI, concluding that dexamethasone suppresses endogenous cortisol production which may increase the risk of bacterial infection without affecting the clinical outcome as compared to patients treated without dexamethasone.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Specifically, the studies had a higher frequency of bacterial pneumonias during the intensive care course in patients treated with dexamethasone as compared to patients who did not receive dexamethasone. One study reports bacterial pneumonia in 7/13 patients treated with dexamethasone versus 2/12 patients who were not treated with dexamethasone.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Similarly, the other study reports bacterial pneumonia in 6/12 patients treated with dexamethasone versus 2/12 patients who were not treated with dexamethasone.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e These studies suggest that endogenous cortisol production is sufficient in management of pediatric TBI. Furthermore, two studies report that dexamethasone therapy amplifies the already heightened post-traumatic catabolic response\u0026mdash;measured by total urinary nitrogen loss\u0026mdash;in pediatric patients with head injuries, potentially contributing to increased muscle protein breakdown and acquired malnutrition.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e One study revealed that patients treated with dexamethasone had a significantly higher daily total urine nitrogen loss compared to patients treated without dexamethasone (256\u0026thinsp;\u0026plusmn;\u0026thinsp;24 mg/kg/day vs. 172\u0026thinsp;\u0026plusmn;\u0026thinsp;29 mg/kg/day; p\u0026thinsp;\u0026lt;\u0026thinsp;0.02).\u003csup\u003e44\u003c/sup\u003e The studies suggest that steroid use mandates aggressive nutritional support in the management of children with head injuries. Additionally, one study reports that dexamethasone administration had no statistically significant effect on ICP or neurological status when high-dose (24 mg/mL) dexamethasone, low-dose (4 mg/mL) dexamethasone, and placebo-treated patients were compared. The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eA subgroup proportional analysis was completed to compare patients who received dexamethasone with patients who did not (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). A p-value of \u0026le;\u0026thinsp;0.05 was used to identify statistical significance. From our analysis, we found that patients who suffered from infection following surgery were more likely to receive dexamethasone (52.01% vs. 16.67%, p\u0026thinsp;=\u0026thinsp;0.0049), although the papers did not define if dexamethasone was given preoperatively, perioperatively, or postoperatively. Interestingly, patients who displayed an improvement in neurologic status following treatment were more likely to have received dexamethasone (80.58% vs. 58.71%, p\u0026thinsp;=\u0026thinsp;0.0347) while patients who displayed a decline in neurologic status following treatment were less likely to have received dexamethasone (19.42% vs. 41.29%, p\u0026thinsp;=\u0026thinsp;0.0347). Additionally, in comparing variables among patients with mild/moderate TBI vs. severe TBI (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), we found that use of dexamethasone was not significantly different between the two groups (64.94% vs. 50.15%, p\u0026thinsp;=\u0026thinsp;0.599).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMild/Moderate vs Severe TBI in Retrospective Studies\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSevere TBI Prevalence (%) [CI]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of Studies (Severe)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMild/Moderate TBI Prevalence (%) [CI]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of Studies (Mild/Moderate)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eZ-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.09 [6.31\u0026ndash;7.86]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.92 [6.72\u0026ndash;9.11]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-1.144\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.253\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGCS Score\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.00 [4.44\u0026ndash;5.57]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.37 [9.25\u0026ndash;13.50]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-5.678\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001 ***\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eConservative Management\u003c/strong\u003e (Dexamethasone)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e79.49 [59.85\u0026ndash;99.14]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e94.50 [86.96\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-1.398\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.162\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDexamethasone Use\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e64.94 [41.61\u0026ndash;88.28]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e50.15 [0.26\u0026ndash;100]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.526\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.599\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eInitial Bolus Given\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e53.36 [26.57\u0026ndash;80.15]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e48.39 [0\u0026ndash;134.93]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.108\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.914\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean Length of Follow-Up (months)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.00 [4.44\u0026ndash;5.57]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.37 [9.25\u0026ndash;13.50]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-5.678\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001 ***\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur systematic review provides further insight into the clinical landscape surrounding the use of dexamethasone in the management of pediatric neurosurgical trauma. Currently, there are no standard practice guidelines regarding the use of dexamethasone within this patient population, though there is recommendation against its use in severe TBI based on few and small studies. Thus, we performed an extensive systematic review and proportional meta-analysis to assess current recommendations, suggestions, and outcomes in studies utilizing dexamethasone for pediatric neurosurgical trauma.\u003c/p\u003e\u003cp\u003eRecommendations surrounding the use of dexamethasone in pediatric neurosurgical trauma management varied among the reviewed studies, with an equal number of articles supporting or opposing dexamethasone therapy. The support for dexamethasone use stemmed from the therapeutic benefit it provided in those studies, such as improvements in functional status, resolution of clinical symptoms, and a reduction in mortality rates. The opposition to dexamethasone use stemmed from its significant side effects or lack of clinical benefit in groups that received dexamethasone as compared to those that did not. Common side effects detailed in the reviewed studies included an increased incidence of bacterial pneumonia and a hypermetabolic state leading to acquired malnutrition and muscle degeneration.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eSupport for Dexamethasone Use\u003c/h2\u003e\u003cp\u003eSupport for dexamethasone use in the reviewed studies centers around the therapeutic benefit it provided in the management of traumatic neurologic injury within the pediatric population. In several studies, dexamethasone was associated with improvement in neurologic status, resolution of clinical symptoms, and reduction in mortality rates. Such studies include reduction in ICP and improvement in neurologic status in patients with severe head injury following trauma.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003eNotably, only 4 patients were included across the case reports. Among the retrospective series, the studies comparing improvement in clinical course and mortality as a result of steroids did not account for confounding variables. Of the studies reporting reduction in ICP after steroid therapy, there were only 5 patients.\u003c/p\u003e\u003cp\u003eA case report by Du Plessis (N\u0026thinsp;=\u0026thinsp;3), et al. elaborated on how high-dose dexamethasone therapy rapidly resolved uncontrollable ICP refractory to other conservative therapies in three pediatric patients with severe head injuries.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e The study suggested that high-dose dexamethasone might have played a significant role in the management of pediatric patients with moderate head injuries, focal lesions unresponsive to surgery, and increased ICP. However, the study noted that the administration of pentobarbital therapy prior to dexamethasone might have enhanced the effects of dexamethasone in the patient cohort, although further study was necessary to confirm these findings. Furthermore, a study by Bruce (N\u0026thinsp;=\u0026thinsp;53), et al. reported that aggressive control of ICP with high-dose dexamethasone reduced the likelihood of secondary injury and diminished mortality and morbidity rates in pediatric patients with severe head injury.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e Comparably, a study by Gobiet (N\u0026thinsp;=\u0026thinsp;93), et al described a reduction in mortality in pediatric patients with severe head injuries from 45\u0026ndash;16% with the use of high-dose dexamethasone therapy.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e A similar study by Gobiet, et al. exhibited a significant reduction in mortality (41.7% vs. 15.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (N\u0026thinsp;=\u0026thinsp;205) and improved return to neurologic baseline in a cohort of severely head-injured pediatric patients who received high-dose dexamethasone as compared to a cohort who did not receive dexamethasone therapy.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e The study attributed the improved clinical outcomes to dexamethasone\u0026rsquo;s ability to considerably reduce the number of abnormal rises in ICP and incidence of secondary complications. However, the study noted that direct measurement of ICP was imperative as abnormal rises in ICP might still occur even when high-dose dexamethasone was administered. Finally, a study by James, (N\u0026thinsp;=\u0026thinsp;9) et al. examined the impact of high-dose dexamethasone, low-dose dexamethasone, and no dexamethasone on the clinical outcomes of pediatric patients with severe closed head injury.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e The study found that patients who received high-dose dexamethasone had a greater reduction in ICP, shorter ICU and hospital stay, faster improvements in neurologic deficits, greater returns to neurologic baseline, and significantly better quality of survival, without significant complications, as compared to the low-dose dexamethasone and no dexamethasone cohorts. The study accredited these outcomes to dexamethasone\u0026rsquo;s anti-edematous properties in addition to its capacity to improve cell metabolism, strengthen cell membrane and blood-brain-barrier integrity, encourage intracranial compliance, and stabilize cerebral blood flow. None of the patients within the aforementioned studies experienced significant complications secondary to dexamethasone therapy.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eOpposition to Dexamethasone Use\u003c/h2\u003e\u003cp\u003eOpposition to dexamethasone use in the reviewed studies stems from the complications and side effects associated with dexamethasone therapy, in addition to the expressed lack of clinical benefit in cohorts treated with dexamethasone as compared to cohorts treated without dexamethasone. Common side effects included gastrointestinal bleeding, hyperglycemia, hypertension, infections, prolongation of the catabolic phase, sodium retention, and potassium excretion, which might contribute to avoidable morbidity and mortality.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA study by Fanconi, et al, reviewed the clinical effectiveness of high-dose dexamethasone therapy in pediatric patients with severe head injury.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e The results of the study ultimately discouraged the use of dexamethasone in pediatric neurosurgical trauma on the premise that dexamethasone suppresses endogenous cortisol production, contributing to an increased risk of bacterial infections. The study had an incidence of bacterial pneumonia in 53.8% of patients within the dexamethasone-treated group versus 16.7% of patients within the non-dexamethasone-treated group. Furthermore, the study determined that there was no statistically significant difference in the clinical outcomes and laboratory data between patients treated with high-dose dexamethasone in relation to those treated without dexamethasone. The study argued that endogenous steroid production was sufficient in eliciting maximum glucocorticoid effects, contributing to membrane stabilization and prevention of brain edema, and that exogenous steroids did not display any additional therapeutic benefit. A study by Kloti, et al, shared this sentiment, endorsing that endogenous steroid production alone was sufficient in the management of severe pediatric head injury and that routine administration of dexamethasone should be reevaluated.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA study by Ford, et al found that dexamethasone therapy increased the existing accelerated post-traumatic catabolic response in pediatric patients with head injuries, contributing to elevated muscle protein breakdown and acquired malnutrition.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e The article suggested the addition of aggressive nutritional support in pediatric patients with head injuries managed with steroids to counterbalance the hypermetabolic state and offset secondary complications. Nevertheless, the study recommended the removal of dexamethasone from the management of pediatric patients suffering head injuries due to these findings. A study by Andrassy, et al had similar findings and further discussed how malnutrition secondary to the systemic hypermetabolism following traumatic neurologic injury can increase the likelihood of morbidity and mortality.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e An article by Cooper et al, found no significant effect on ICP patterns, neurological status, and morbidity or mortality when low-dose or high-dose dexamethasone was administered to adult and pediatric patients with severe head injury in comparison to placebo-treated patients.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\u003ch2\u003eDexamethasone Use in Severe TBI vs. Mild/Moderate TBI\u003c/h2\u003e\u003cp\u003eNine of the reviewed studies discussed dexamethasone use in pediatric patients with severe TBI\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Of the nine, both support for and opposition to dexamethasone use were of equal amounts. Support for dexamethasone use in severe TBI were based on clinical results suggesting improved clinical outcomes following dexamethasone administration. Specifically, patients with severe TBI that received dexamethasone therapy exhibited reduced mortality rates, greater improvements in neurological status, decreased ICP status, and shorter ICU and hospital stays.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e Opposition to dexamethasone use in severe TBI centered around clinical results suggesting that dexamethasone has no effect on clinical outcomes and may increase risk of infection.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e These studies suggested that endogenous cortisol production was sufficient for management of severe TBI in pediatric patients.\u003c/p\u003e\u003cp\u003eThree of the reviewed studies discussed dexamethasone use in pediatric patients with mild or moderate TBI.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e Of the three, one study expressed strong support for dexamethasone use following results demonstrating decreased ICP status and improved neurologic status in pediatric patients that received dexamethasone therapy following mild/moderate TBI.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e The results of the other two studies suggested that dexamethasone therapy increased the existing accelerated post-traumatic catabolic response in pediatric patients with mild/moderate TBI, contributing to elevated muscle protein breakdown and acquired malnutrition.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003eCurrent guidelines on the use of dexamethasone in adult traumatic brain injury (TBI)\u003c/h2\u003e\u003cp\u003eThe Corticosteroid Randomization After Significant Head Injury (CRASH) trial was a placebo-controlled trial of 10,008 adults with TBI that found that corticosteroids should not be routinely used to manage TBI in adults.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The results of the trial revealed that patients who received corticosteroids (methylprednisolone) had a higher risk of severe disability or death than those who received a placebo. The findings of the study concluded that corticosteroids should not be routinely used to treat TBI. Similarly, the Brain Trauma Foundation Guidelines for the Management of Severe TBI, 4th Edition also recommends against the use of corticosteroids to treat TBI in adults.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\u003ch2\u003eCurrent guidelines on the use of dexamethasone in pediatric traumatic brain injury (TBI)\u003c/h2\u003e\u003cp\u003eAccording to the most recent edition of the Brain Trauma Foundation Guidelines for the management of pediatric severe TBI, the use of steroids was not suggested to improve outcome or reduce ICP.\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e Only two small and outdated studies\u0026mdash;both included in our meta-analysis\u0026mdash;were used to support the recommendation. These studies, conducted by Kloti and Fanconi and published in 1987 and 1988, included 24 and 25 patients, respectively.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Nevertheless, although dexamethasone has been found to offer significant clinical benefit in the management of pediatric neurosurgical cases, mainly tumors, the adverse effects related to dexamethasone administration in this population must also be considered. The main reported adverse effects of dexamethasone administration have included infectious, gastrointestinal, psychological, and growth abnormalities.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003c/sup\u003e These side effects are dose-dependent with a direct correlation between dexamethasone treatment length and adverse effect incidence.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Thus, dexamethasone administration requires careful consideration regarding dosing and duration to ensure its safety and efficacy in the pediatric population.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis systematic review and proportional meta-analysis was limited by the number and type of studies we were able to include. We identified only 13 studies, of which 2 were case reports and 11 were retrospective/prospective series. Heterogeneity across study designs, patient populations, dosing regimens, comparators, and outcome definitions was high; most included studies were small, single-center, and several were conducted decades ago, which limits generalizability and increases the potential for bias. As a result, pooled estimates should be interpreted cautiously. We were unable to evaluate many clinically relevant subgroups, and findings may be confounded by indication and center-level practice patterns. Future prospective, adequately powered studies using standardized definitions and outcomes are needed.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eDexamethasone is a commonly used glucocorticoid with many roles in a neurosurgical setting. From the studies included in this systematic review of dexamethasone use in pediatric trauma, most studies reported limited or no benefit and increased complications such as gastrointestinal bleeding, hyperglycemia, hypertension and infections. A few other studies, published in the late 1970s and 1980s, reported its benefits such as improvement in clinical symptoms, reduction in ICP and reduction in mortality rates. In pooled proportional analyses, neurological improvement was more frequent among dexamethasone-treated patients, but infections were also more common, underscoring equipoise. At this time, however, we are unable to make a recommendation for or against its use due to the limited number and poor quality of studies regarding dexamethasone use in the management of TBI. Thus, more research is required to fully understand the effects of dexamethasone in the setting of pediatric neurosurgical trauma and create guidelines for its use.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests and Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was provided, and the authors have no competing interests as defined by Springer.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlali AS, Gomez D, Sathya C, Burd RS, Mainprize TG, Moulton R et al (2015) Intracranial pressure monitoring among children with severe traumatic brain injury. 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Pediatr Crit Care Med 20(Suppl 1):S1\u0026ndash;S82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/PCC.0000000000001735\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0000000000001735\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dexamethasone, Trauma, Neurosurgery, TBI, Pediatric, Conservative, Steroid","lastPublishedDoi":"10.21203/rs.3.rs-7467090/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7467090/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSystematic Review with Proportional Meta-Analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDexamethasone use in pediatric neurosurgical trauma remains controversial, with varying reports of its overall efficacy. Our study aims to assess the use of dexamethasone in pediatric neurosurgery regarding patient characteristics, risk factors, and dosing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA systematic review was conducted using PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify literature presenting dexamethasone use in pediatric neurosurgical trauma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 597 publications were identified, of which 13 met inclusion criteria (2 case reports, 11 retrospective studies). Case reports (N=4 patients, mean age 13.5 years) demonstrated traumatic brain injury with cerebral edema, hematoma, or swelling. All patients received dexamethasone (5–7 days), experienced no treatment-related complications, and 75% showed neurological improvement. Across 11 retrospective studies (N=493 patients, mean age 7.3 years), most presented with severe TBI and cerebral edema. Management strategies included conservative therapy (83%) or surgical intervention (13%). Dexamethasone was used in 61% of patients (average 0.92 mg/kg/day for 4.7 days). Reported outcomes were mixed: some studies demonstrated reduced mortality, improved neurological recovery, and lower ICP with dexamethasone, while others reported increased infection risk, catabolic effects, and no significant benefit. Pooled subgroup analysis showed patients who improved neurologically were more likely to have received dexamethasone (80.6% vs. 58.7%, p = 0.0347), whereas those who declined were less likely to have received it (19.4% vs. 41.3%, p = 0.0347). Infection was more common in dexamethasone-treated patients (52.0% vs. 16.7%, p = 0.0049).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEvidence regarding dexamethasone use in pediatric traumatic brain injury is conflicting. Although some older studies suggest benefits including reduced ICP and mortality, most studies report limited efficacy and increased complications such as hyperglycemia, hypertension, gastrointestinal bleeding, and infections. Given the small number of available studies, no definitive recommendation can be made at this time. Further high-quality research is needed to clarify its role and establish guidelines for use in pediatric neurosurgical trauma.\u003c/p\u003e","manuscriptTitle":"Dexamethasone Use in Pediatric Neurosurgical Trauma: A Systematic Review and Proportional Meta-Analysis of the Current Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 10:06:54","doi":"10.21203/rs.3.rs-7467090/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bc11b6be-7535-462f-afed-45adb691c373","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-02T21:23:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 10:06:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7467090","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7467090","identity":"rs-7467090","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}