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Physiologic Characteristics of Hyperosmolar Therapy After Pediatric Traumatic Brain Injury.

ABSTRACT: All work was performed at the Barrow Neurological Institute at Phoenix Children's Hospital. Objective: Investigate injury severity, neuroimaging, physiology, and outcomes with bolus hyperosmolar therapy (HT) of 3% hypertonic saline or mannitol. Methods: Retrospective cohort analysis was performed. Physiologic variables included intracranial pressure (ICP), arterial blood pressure (ABP), and heart rate (HR). Volume-pressure compensation (PVC) indices included ICP pulse amplitude (AMP) and correlation of AMP and ICP (RAP). Cerebrovascular pressure reactivity (CVPR) indices included pressure reactivity index (PRx), pulse amplitude index (PAx), wavelet PRx (wPRx), and correlation of AMP and cerebral perfusion pressure (RAC). Heart rate variability (HRV) indices included heart rate standard deviation (HRsd), heart rate root mean square of successive differences (HRrmssd) and low-high frequency ratio (LHF). Outcome was assessed using Glasgow Outcomes Scale Extended Pediatrics, 12-months post-injury. Generalized estimating equations was applied to investigate associations of physiologic changes and pre-treatment indices with HT efficacy. Repeated measures analysis of variance was applied to investigate changes after HT without intracranial hypertension (ICH). Wilcoxon rank-sum was applied to investigate HT responsiveness with age, injury severity, neuroimaging, and outcomes. Results: Thirty children received bolus HT. ICH reduction after HT was associated with reduced ICP (p = 0.0064), ABP (p = 0.0126), PRx (p = 0.0063), increased HRsd (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wPRx (p = 0.0072). HT-responsive patients were older and had improved outcomes (p = 0.0394). HT without ICH was associated with increased ICP (P < 0.0001) and ABP (P < 0.0001), increases in all HRV indices and decreases in all PVC indices. Conclusion: After pediatric TBI, efficacious HT is associated with decreased ICP and ABP, pre-treatment indices suggesting efficient CVPR, and potentially improved outcomes.

SUBMITTER: Wellard J

PROVIDER: S-EPMC8093760 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePediatric mild traumatic brain injury (TBI) and concussion are a public health challenge with up to 30% of patients experiencing prolonged recovery. Pediatric patients presenting to concussion clinics often have ongoing impairments and may be at increased risk for persistent symptoms. Understanding this population is critical for improved prognostic estimates and optimal treatment.ObjectiveTo describe pediatric patients presenting to concussion clinics and characterize factors associated with their recovery.Design, setting, and participantsThis prospective cohort study included patients enrolled at multicenter concussion specialty clinics from the Four Corners Youth Consortium from December 2017 to July 2019, with up to 12-month follow-up. Patients were eligible if they were aged 5 to 18.99 years with a diagnosis of mild TBI or concussion presenting to participating clinics within 8 weeks of injury. Patients were excluded if the patient or their parents were unable to read or sign the consent document, or if the patient had a Glasgow Coma Scale score less than 13 or a penetrating injury. Data were analyzed from February 2019 to April 2020.ExposuresDiagnosis of mild TBI or concussion.Main outcomes and measuresThis study used National Institute of Neurological Disorders and Stroke common data elements, including data on demographic characteristics, injury details, history, neurological and neuropsychological assessments, and treatment.ResultsA total of 600 patients were consecutively enrolled, among whom 324 (54.0%) were female and 435 (72.5%) were adolescents (ie, aged 13-18 years). A higher proportion of girls and women (248 patients [76.5%]) were adolescents compared with boys and men (187 patients [67.8%]) (P = .02), and girls and women reported significantly more preexisting anxiety compared with boys and men (80 patients [26.7%] vs 46 patients [18.7%]; P = .03). Significantly more adolescents reported preexisting migraines compared with preadolescents (82 patients [20.9%] vs 15 patients [10.9%]; P = .01). Girls and women recovered more slowly than boys and men (persistent symptoms after injury: week 4, 217 patients [81.6%] vs 156 patients [71.2%]; week 8, 146 patients [58.9%] vs 89 patients [44.3%]; week 12, 103 patients [42.6%] vs 58 patients [30.2%]; P = .01). Patients with history of migraine or anxiety or depression recovered more slowly than those without, regardless of sex.Conclusions and relevanceThese findings suggest that identification of subgroups of pediatric patients with mild TBI or concussion at risk for prolonged recovery could aid in better prognostic estimates and more targeted treatment interventions.

Project description:To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury.National Library of Medicine PubMed literature review.The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult traumatic brain injury is reviewed.Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human phase II trials of progesterone for adult traumatic brain injury have been published, and two multicenter phase III trials are underway.The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of traumatic brain injury. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, and statue epilepticus).

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Physiologic Characteristics of Hyperosmolar Therapy After Pediatric Traumatic Brain Injury.

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